<%BANNER%>

Syntheses and Studies of Perfluoroalkyl Substituted Compounds

xml version 1.0 encoding UTF-8
REPORT xmlns http:www.fcla.edudlsmddaitss xmlns:xsi http:www.w3.org2001XMLSchema-instance xsi:schemaLocation http:www.fcla.edudlsmddaitssdaitssReport.xsd
INGEST IEID E20101123_AAAACX INGEST_TIME 2010-11-23T15:48:56Z PACKAGE UFE0011625_00001
AGREEMENT_INFO ACCOUNT UF PROJECT UFDC
FILES
FILE SIZE 31970 DFID F20101123_AABSMP ORIGIN DEPOSITOR PATH pooput_c_Page_042.pro GLOBAL false PRESERVATION BIT MESSAGE_DIGEST ALGORITHM MD5
281c33878c0f73548de64c4742dc158e
SHA-1
3cad87699ac2c6331905911489e3581c1348cb85
40746 F20101123_AABSND pooput_c_Page_062.pro
d6a8d70a6c1bbabf6410290c3b546437
803244f61d3074248a9eba0fc71778ababed58d0
39588 F20101123_AABSMQ pooput_c_Page_043.pro
63fb156c73b08e23b4a9ceefda45f3d2
8f01575e0a589d5698a80ad9a710ea981f7b52e0
31476 F20101123_AABSNE pooput_c_Page_064.pro
a62b343549df0cfd7e2fb30c5e35a66f
c67a941da29db96fc1d4009c4f8f14f897ae9464
20125 F20101123_AABSMR pooput_c_Page_045.pro
b3de19f27b99353609c2b5a405cb789d
01a44632b06721edba80bf82afc38e77d7b3d2cb
46034 F20101123_AABSNF pooput_c_Page_065.pro
d1e1884001ac431c5b77cd7c9a6a9f3b
840add66c92b1f9d1d25f8dedf8f070994e557bd
9617 F20101123_AABSMS pooput_c_Page_046.pro
981b7dea49c4bfc0c3935cc4cdce9778
6133fb0f44737748a8f61a75468900653ff65cad
38853 F20101123_AABSNG pooput_c_Page_066.pro
b57d1307336c18ec6ed42b8c3a57b9ca
37f09f7c9b888282b2779965325e9aedef67a989
33299 F20101123_AABSMT pooput_c_Page_048.pro
63ded1bcd1f3ed42987f8d4e243a41b3
56b9d4ddfa70b5ae63235cd92876d98f50313675
42013 F20101123_AABSNH pooput_c_Page_067.pro
3b3d2cfbc3771df34d0c3c580afb2e77
4207efab12af8160306eabf886857c8dbef59068
20669 F20101123_AABSMU pooput_c_Page_049.pro
92a72a2686b0b609a83e29db6077d108
24a7db2e7d89cbc57d9e1b2fd13b23af473b0324
4573 F20101123_AABSNI pooput_c_Page_068.pro
0e4bd609262784eb8d8930a255331d2e
b4fd20f7f876999366ff2fe7b120ce81f2aaeda2
38232 F20101123_AABSMV pooput_c_Page_050.pro
ab0168f8e19630a5d3b8cf12a055dc99
42875cf759c2eb34dfe9371a100dd3e412fe7818
25200 F20101123_AABSNJ pooput_c_Page_070.pro
5a2cf86cee79acb2c1c1dd6556d98f4d
139e7df26c835737b997b719ec9b95b8e30bf90c
44936 F20101123_AABSMW pooput_c_Page_051.pro
14bfb5303b90ee5524476b4b911594ef
f5ec9b494935b708241c31fa7ad3d46ac59da11b
31698 F20101123_AABSNK pooput_c_Page_071.pro
96cda2571c1f66c69985c64f6a7ec1a4
802c28b64c9b873d97ad121c50b41006ee89df5f
36733 F20101123_AABSMX pooput_c_Page_052.pro
915d852f4ce272276128d2a9b283033d
af98dfbad76af39ffb51bde5e05608ee437594ab
18955 F20101123_AABSOA pooput_c_Page_095.pro
aba8b6e3c582d4d611ed1c7216d62685
b0f27e6cd0348ba2c63c29e43adc6c773bd795fa
41823 F20101123_AABSNL pooput_c_Page_073.pro
8a2c43627f286549922b755cfca73f05
63704725ca4b23cc64d0d8cbbaa700d393ac6f8f
39272 F20101123_AABSMY pooput_c_Page_055.pro
1c15b8ca61a9ab6b9a71ccbd9683d197
4040fa0330744f485a8e33f586bc51c30ae1f9c0
24023 F20101123_AABSOB pooput_c_Page_098.pro
f26ff5e571c7e8e55e924778e0840c7b
59552101034cd3b7a79a55190168986994b68e9e
33295 F20101123_AABSNM pooput_c_Page_075.pro
11ef495760c93e2816e30e39dfddce41
ba87a7881d49fe34733397695d8c98191aece453
35298 F20101123_AABSMZ pooput_c_Page_056.pro
83d4d5580f3d8b19b85d024fcc3cc833
21b1bd5b492a375443b29e1253d11894a9f89c7c
26338 F20101123_AABSNN pooput_c_Page_076.pro
b342030fadb1b2eb98a50945ed47cd7b
d9af3d52dee7642a15be5b73f926849b5570a8cf
23458 F20101123_AABSOC pooput_c_Page_099.pro
e4ffee4e8cca94fa404013196c4096bd
12e4ac8f3121e2e6b1b1630f26b543b868cf44a6
44124 F20101123_AABSNO pooput_c_Page_077.pro
2e645cea9e29347ed3335a4b29e342a5
788763d633b74a7a3f20f460d213f9490ede5c49
15278 F20101123_AABSOD pooput_c_Page_100.pro
e00b463876a9f5797b160ec35f7c3515
750ff838eff1a97e8f174df796823279049e598c
43718 F20101123_AABSNP pooput_c_Page_078.pro
b44c7661278ca931b2a788823b092d76
148dded85275d8a385cd8c6d1fc2758e1ab5cd68
18185 F20101123_AABSOE pooput_c_Page_101.pro
025a9f6cb557f6d2c2e4eb3b58001cb3
c39137751544633a133dd92d608f0ca273617906
42575 F20101123_AABSNQ pooput_c_Page_080.pro
bb6c22207c2aa0452653eaa58952f351
6e3a6525501e9293df3a664f3eeaf918389ab8b1
16354 F20101123_AABSOF pooput_c_Page_102.pro
bca404e3fb652e607976293d3b19a948
97999b7f15fb6c49450cb152222f05473613c670
32578 F20101123_AABSNR pooput_c_Page_081.pro
bb251a369a562a41ce93f6640ff154a8
f032f1c970514d6c775fea5d8a66f015fec33e26
17735 F20101123_AABSOG pooput_c_Page_105.pro
cf602622bfc08bed74c66a48ba37cc08
c0e3cfa9092525d54f113979a60544d479f48a22
33161 F20101123_AABSNS pooput_c_Page_085.pro
967bcf6d6a0e55e8817426f514009333
cb1ee535288e36672e0e21f08c582c1a6a609a87
12693 F20101123_AABSOH pooput_c_Page_106.pro
ce2aae8c901911581346f5fa4cba8eb0
882b6e44e95081c8c21c50a8a38e965daab805f7
29784 F20101123_AABSNT pooput_c_Page_087.pro
3020671c7ad6346c73e0b7090eb78021
1a07bb7e5a292aabcc2ae56f033d1958255ca044
34718 F20101123_AABSOI pooput_c_Page_109.pro
04df0d3b2d8907d52c6de9638095a7a1
c61f7aab59075e75d6d7e676877a26045b818d80
35774 F20101123_AABSNU pooput_c_Page_088.pro
36c276605838e372163a148b143b280a
4ba176c2b6b79f0e24ff728b12789b549233c79c
30231 F20101123_AABSOJ pooput_c_Page_110.pro
2596d6ab53c93b65401d3d5a468befe1
4c00faf0e78ffa9ad1dd51edbad69fd4a4a17e55
9219 F20101123_AABSNV pooput_c_Page_090.pro
a40748bfa9dd4ab63dc655bf4c0fe254
f2f47c70f205051e704c9ed9bf41acd249968428
1612 F20101123_AABSOK pooput_c_Page_111.pro
7c765652ac96d40979d169e612b76d96
ea900f82c8c1184f5fc88c60aff4f2fbc4e59e16
29165 F20101123_AABSNW pooput_c_Page_091.pro
328295db4f778a3bcd0d66537211730c
a5b7a6ef4361b74bed133800d78cc3cda5df98b3
15481 F20101123_AABSOL pooput_c_Page_114.pro
fe74a8ab385ce2f8711143ae17aa2c77
99f97595165336bbcb828a7bd540f4be48bada68
27567 F20101123_AABSNX pooput_c_Page_092.pro
c27194d730ffd68d99c2b72a348b917a
732232fa195978e0cd84ab7a40536c1f488a9c66
53435 F20101123_AABSPA pooput_c_Page_136.pro
7a4795a04fd9a09a57c2aea34bc92bc2
ded88454e0c9744d152e724f61cb542f3b8bfea0
13321 F20101123_AABSOM pooput_c_Page_115.pro
cd701eeb4181deaf586b4247c69dba84
8dfea501a57e78d19817e3673ab7026393c5a9ed
16488 F20101123_AABSNY pooput_c_Page_093.pro
ac0a068e35d44f51a5b41677a1c3346b
0b4a2d6782e36d34177d9f29e22344441f6393c2
47057 F20101123_AABSPB pooput_c_Page_137.pro
27f235bd3f73d82b82292933f3fe56db
616f0a3bde386244ce756b5b46443bfe6b20152d
18763 F20101123_AABSON pooput_c_Page_116.pro
21989229598b747c99b75f1e7c9b804a
210e9f57b499337465cbf03dec51b3b979178bc8
28191 F20101123_AABSNZ pooput_c_Page_094.pro
9c3c1869c66fe3de7079f0ff11441bd2
427835662ff69b95ce9290aa78d5e86c9a713383
14151 F20101123_AABSPC pooput_c_Page_138.pro
152efe34fa80283ec0b77a3423ec3fe3
b3ee12cfaa67851a9364749c52b7da21f63322aa
12091 F20101123_AABSOO pooput_c_Page_117.pro
928fe76db11b8d141ad0fa87df940059
956d8f69e4288e1c2ecb7b07b73aa4c2f01fc70d
18089 F20101123_AABSOP pooput_c_Page_118.pro
7aeafc40816a7a9546a382bb0e873601
2acde5255bdcb676d0502c49aaf3babd8770c731
36973 F20101123_AABSPD pooput_c_Page_139.pro
478432b1465303df313d0e16381b0999
ab7346153fda7e932cd7f321fa6496503f5a2e8f
16766 F20101123_AABSOQ pooput_c_Page_123.pro
ab57584add257a174edeff2f7d702eb5
61c0a2ff91f799230c2218641d263f92f52d7163
439 F20101123_AABSPE pooput_c_Page_001.txt
8f24699fe776a900cd98ab1f0aaa95d2
a12578fe038a606f44a355214e006ed84de471fc
17890 F20101123_AABSOR pooput_c_Page_124.pro
acf7c43c8ff66bb6a8752fe41fe9c368
5dcea87fe6890baeead4770b509b7a54aec76be9
127 F20101123_AABSPF pooput_c_Page_002.txt
ec6827571235840e2331ac61174d3a5f
840a9f0dbda6c2c8eff3a924179b01f3ed20d06d
13359 F20101123_AABSOS pooput_c_Page_127.pro
faed252d799666d639106be6218f246f
46a5110710b1cf2ec6285594393b152f5ab82160
1639 F20101123_AABSPG pooput_c_Page_003.txt
e11c13ce84fe6e2312659b4de0cb1f59
a58dfca4b9c8b0363580b735b341fa57f607d44d
16787 F20101123_AABSOT pooput_c_Page_128.pro
b22210e186ab7282127176964218624e
b57ce69434a611fcec21826c097cee0444e7bcff
3828 F20101123_AABSPH pooput_c_Page_005.txt
4862b463054465821129b5e3724bd6ac
44282946853f9bd40f0d93e7859e339b73361160
15569 F20101123_AABSOU pooput_c_Page_129.pro
14452a1dc86576f311259681177376d4
de90a07e8531e127afd3910154dc875afed5bcc6
894 F20101123_AABSPI pooput_c_Page_007.txt
a3b62493fa24a76cb885528241d46054
648b38d1a60f372b910a58a8d1672e96d7c81e23
18137 F20101123_AABSOV pooput_c_Page_130.pro
63a33c125f2c4bcc5bdbe18ae6e18dba
d4a33ea746ae21734e14f0253a25cec09276966f
2289 F20101123_AABSPJ pooput_c_Page_008.txt
9f1070a5754c1c147adf70ec1c6108fb
b312243f41707f3a320418c2fc3e482f9e7bf90d
13273 F20101123_AABSOW pooput_c_Page_131.pro
b68a77888ad6dc750ac4a505052b9db2
6b7f6eb09ac4ac9f91c5d49a234e929844dcfe15
2195 F20101123_AABSPK pooput_c_Page_010.txt
8b2b32f18d96b006c0d0b356217c08b1
b7776e46d69675b4e499fbf54952b9ece950a890
38106 F20101123_AABSOX pooput_c_Page_132.pro
101b062bec5e83a2c335942eb8c29fea
6da68f295926bcd566cf211fe7028245df434b62
1280 F20101123_AABSQA pooput_c_Page_029.txt
b265b5b7f9c7bd9bec5d40d30bb8664a
be6d7799df20987716dbc62aa11ba96a54a657c1
2568 F20101123_AABSPL pooput_c_Page_011.txt
4cf21348d375729dc7981f02dc88cf20
f6029182846c943e5210b1ebe10685a6306c6484
37236 F20101123_AABSOY pooput_c_Page_133.pro
3f8d5aa1e1c59f70bbd73c0f60c89781
0a1ddedcf1fb44cb1002af594d2bfd6302cf5fdb
1844 F20101123_AABSQB pooput_c_Page_033.txt
0cf03889729734cf64b32dbbc44c6f41
026ff3f67b4b8902b700c5b46c7c7cdc9eb06f6d
1080 F20101123_AABSPM pooput_c_Page_012.txt
948292d19b4fe8abe16245a35c076f17
909508c23238673775e620481075dfa86f8afc0f
52348 F20101123_AABSOZ pooput_c_Page_134.pro
8d2a1af7edaa5d1a9cfafb1686013266
526af9ba48c73c6c7e42f81b31054eebe7a348b3
1814 F20101123_AABSQC pooput_c_Page_034.txt
94adfd49e1ea8ad32fe0153f99d0b600
25fb0e079288aaa416672ed828b066bdd61bd69b
2171 F20101123_AABSPN pooput_c_Page_013.txt
3203144aef6864c747f97abc27889b42
a1e72b7eeac35dbcc3dfdfd92624a33fba8c9ece
1903 F20101123_AABSQD pooput_c_Page_035.txt
7eb6903528a92b4e33f956ef1201d074
6d13906fb40dedfc1825afa535ffe4c0deb703c2
2791 F20101123_AABSPO pooput_c_Page_014.txt
c0b43f046e37ea774e83d51f0c9e8c02
a8f4d3ab7995d6b5eec5913b7d8a4994449fe665
1573 F20101123_AABSPP pooput_c_Page_016.txt
17479b3c1440137424e830c243af0068
3b2b082fff96a10e95e3de1a6196297cb980735c
1832 F20101123_AABSQE pooput_c_Page_036.txt
3e35e40bb5b90e8ff709961210fe57c0
3d05967b968746aa79538fca4099a109547b59ca
721 F20101123_AABSPQ pooput_c_Page_017.txt
d3fff78c7066e4d0095d7c248676f637
36e51b21e69bbd4ff229e846bfd1503606c822e9
1920 F20101123_AABSQF pooput_c_Page_037.txt
6cfff6110de0903bfffa33ddce44674d
89452c085463225a5f46c8fb1d714346656cd187
1163 F20101123_AABSPR pooput_c_Page_018.txt
5fc1655db077d4677d6b507ffd34501e
76ad1179d5301ac3d460cf52c15f2b94cfe89351
1638 F20101123_AABSQG pooput_c_Page_038.txt
eb1cb08cc0b376133e495be27b67ab92
9058d97325fabeb65e8422d991010073838e54f0
2115 F20101123_AABSPS pooput_c_Page_019.txt
a685104eeca27eba24ccab1411242ab9
7a21853f1ff09588c497bd07f2b6e603e560d89b
1581 F20101123_AABSQH pooput_c_Page_039.txt
8d43fbee2e652dee93eab3aaa7122b15
de40cb3e7845d64390578fbe0d397909971d0255
1905 F20101123_AABSPT pooput_c_Page_020.txt
f898211348edcc02ce769ba5d456ab7a
e01d20dc00c729c0885298dc84e55d6abfcb894c
1460 F20101123_AABSQI pooput_c_Page_040.txt
bd009bc3d70f48838284de2946a3885d
4c69cb260406a5be8a072fad6b343afeede678ee
2074 F20101123_AABSPU pooput_c_Page_021.txt
09ba399204880fdb13787d713f5b5be9
46d7b992c6ae7b94c38440f4ced664c6c2592d14
1535 F20101123_AABSQJ pooput_c_Page_042.txt
b3f51dea2a035b0eb494d4e371ad9642
af6586eb4185999a251995511c9aaf72c2b57df7
1686 F20101123_AABSPV pooput_c_Page_023.txt
3c72062bd1cb3bbf15e5a21b3693f435
162f6ead927df4b995ef20c0317704c90963a211
2055 F20101123_AABSQK pooput_c_Page_043.txt
83cae699c10e2ea49338eae24c7c74c6
1827fac6d0181fc78b4e7737367443de15c4758b
2015 F20101123_AABSPW pooput_c_Page_024.txt
1c655fd48f1bf7fe9a55c9ebc6a29471
ab44b9c29edb5ffd470192493211648f1a484dd4
1752 F20101123_AABSRA pooput_c_Page_069.txt
68e2e4255387b57c666b5af9ffda88aa
730e2ee99b32aaeb7cf5d2377bdf0963224d99a3
589 F20101123_AABSQL pooput_c_Page_046.txt
baec22f121bfa627ba59385270d49b60
e6d491381a186798d70815444f0690d2e048ac7e
2045 F20101123_AABSPX pooput_c_Page_025.txt
d3e70d3bfc4f4207402994ba1307bd5a
0db65dac40ef14fe0a9ba67653e391399ae0ee52
1449 F20101123_AABSRB pooput_c_Page_070.txt
693969407ebc2908093fa3c48bae38d7
af55928bf6b0dace68fe68e14212e630003f70e8
1592 F20101123_AABSQM pooput_c_Page_048.txt
d34b12c779f8d3d670244b493d093675
19b4aec47a25464202cd4b4695ae134ae6f523bd
1820 F20101123_AABSPY pooput_c_Page_026.txt
977ab5dcc58ea0dbf13d6d75764d77f5
23727eb9bf1c1416111aa144dd73771f5f418e9d
1644 F20101123_AABSRC pooput_c_Page_071.txt
fe7a5d733d92cd2f0de0e903ea362ce2
8ba2e297b84260e18ab3e06e398852f23f3a776c
1353 F20101123_AABSQN pooput_c_Page_049.txt
107e66a34ddd90dd22c64ed835f541a7
fbde5963d834103198f65ed7d5e367bf69564f25
762 F20101123_AABSPZ pooput_c_Page_028.txt
c50cee78f43cf40d46809ff1492abeed
7a6a142059b81ec3db7478befaf90d5cf2ae3b99
1921 F20101123_AABSRD pooput_c_Page_073.txt
8867c13ca69238bf7e18fff3b4886a08
a54d5a064a49551a554a580ec310a3c2c631fd75
F20101123_AABSQO pooput_c_Page_050.txt
4e32d00ca36db9f8153f276ec54430e0
7a0c92a090167cfc2bfbe217be9c84c845940a31
1671 F20101123_AABSRE pooput_c_Page_074.txt
598f602efbbfe0cac7547413c9f3d6a7
5d5459ba36a5e40e0d6416031892e2731ece0e15
1821 F20101123_AABSQP pooput_c_Page_053.txt
2afbd73e9504e6f4056faa9719e75a37
f8f17c8bb13dbe0af0ed386ef46cf1998a943aeb
1526 F20101123_AABSQQ pooput_c_Page_054.txt
867057072c14c5d1996fc45e53cde982
3069d95b25f62dc64a169e3c1657e40c7553d270
1825 F20101123_AABSRF pooput_c_Page_077.txt
91684976b16cd5d1db5895a24de7eade
9eb06e3546fe0fb8beff06b543bf0e2bcc96d875
1589 F20101123_AABSQR pooput_c_Page_055.txt
d241163650a53bd08f9be06c0a60995e
b7ab82a92f03e9faa52cf524213f0fb70605878a
1748 F20101123_AABSRG pooput_c_Page_078.txt
4e6fb934a2e76b3a914172cc16ed7ae6
2a5d9b17fda3fe54b13ade4cbdcfbe510a2a439c
1438 F20101123_AABSQS pooput_c_Page_056.txt
732144ee4bf1832b7d2f487b75a93fe0
e672788912c41e4e4e9877b1f9a0ca1584431152
611 F20101123_AABSRH pooput_c_Page_079.txt
c0f9eb2d1fb10c2957d1d334ce3e1efe
1bbabaa04f2d3792b99b6e5ef1e613362d7ea42f
1345 F20101123_AABSQT pooput_c_Page_059.txt
11a3f3e5111d4c657043a80b8bc80210
4e3b9c6cc98443b329a0fb120243823422be178c
1766 F20101123_AABSRI pooput_c_Page_080.txt
a9175e2a29612afd0dc1d5a990677f34
0dd7b093be0ad5e43d5706efb7163f782d939918
627 F20101123_AABSQU pooput_c_Page_060.txt
8025c82dcca4459f93cc31fc19a12016
53dff196becc691ef5de6b815348e82becca8691
1606 F20101123_AABSRJ pooput_c_Page_081.txt
7aa95fd28fb3cb38559e174209050d68
f92b7c100b155754cd7a38b9c8119fe49aae9194
1437 F20101123_AABSQV pooput_c_Page_061.txt
a698f08b17cbfe26ba8d9b9ee01f29d6
aaea710b72efc2a81f6c4517e44c53f866bb97c8
2011 F20101123_AABSRK pooput_c_Page_082.txt
b1b295e9310128863ff11a11a5b160ec
1ed6d40da5ba1e4249d70b95d4a5507617f56704
1629 F20101123_AABSQW pooput_c_Page_064.txt
9a6d0c62f1d5664a40e24779d2c68a27
6e08f226655570175a1409fa6e707a98b0169f18
1243 F20101123_AABSRL pooput_c_Page_084.txt
31d97dfb93ec44b3642bbbdf9e2057dc
eb16a7f0de858d2892d2e17f9f01fd04a3a85014
1892 F20101123_AABSQX pooput_c_Page_065.txt
00ad965f518f4d7fedbc623831b9151e
4ec60900df1cadc32791b7805d095464b7b869e2
1417 F20101123_AABSSA pooput_c_Page_109.txt
d076507658f086d8dcf2b3b0b2243b31
03e233a80dfc2b77bc11575a15e6f1c4d656efe2
1964 F20101123_AABSRM pooput_c_Page_086.txt
896a0bb431ca800794a860d5da75bf64
a6665eb698bb61561cf8c17eefab6df72102f167
1577 F20101123_AABSQY pooput_c_Page_066.txt
4aefee9cf229128caf8385782fd18ae8
25088b4852695bf37ea619c24d5932f1c4241aa1
1223 F20101123_AABSSB pooput_c_Page_110.txt
dcfbe1015ed877e7c6ab4e0581e045e4
a578099df034bb1c05c9de207e85d1cb7fbbae55
1713 F20101123_AABSRN pooput_c_Page_087.txt
d1e33278642365d12ff31575703892ae
2945f1eb54d95c937effa893e02fa73195530d81
220 F20101123_AABSQZ pooput_c_Page_068.txt
cc06756c2f5586bf874bd8231b9b281b
e2a49a37ad29e84cf0362f5c99a5e4da4547e25f
20990 F20101123_AABRPA pooput_c_Page_038.QC.jpg
8ba0bba32351b97e4b3da2ca7a2d0861
717595caba173df72e01cfe9625db4ddd1bdffeb
122 F20101123_AABSSC pooput_c_Page_111.txt
40f2c813c614fb884f5cce67c2c21a81
6b7c77204c683466922f18c7a1d7a887b06b1b11
999 F20101123_AABSRO pooput_c_Page_089.txt
dfcfc2eb4da22987c0a828ac19743f36
54e502f4077a3dcbd425a6dcb78c375b0510d38c
14291 F20101123_AABRPB pooput_c_Page_096.pro
3a50acaa26ac277088ac01fac81dc61c
1544aa3bca4c856ded1a544489d7e685857234fc
1510 F20101123_AABSSD pooput_c_Page_112.txt
838ee0bc12771a6de1105998cf078432
4ec1d384d944eaf9926a369c231613e7735f89e3
558 F20101123_AABSRP pooput_c_Page_090.txt
8346577663ce99062871030cffee185d
069676f8de2e937716919c25b2f741852e939013
4129 F20101123_AABRPC pooput_c_Page_010thm.jpg
1a78d9e6a622c478edb9d98a06f6d0dc
c1195c562b64846aa8f3f95997f3ba3bd6cf3ecf
628 F20101123_AABSSE pooput_c_Page_113.txt
184caf5cbf4723846ce4d82cd20111c8
d02b41fa10b41bd30a32a5713073dcb7c0df4c05
1482 F20101123_AABSRQ pooput_c_Page_091.txt
cedfba646775c4d9e562e8668fbc0dca
43f69c50e746d344458cd1706632f763288edf37
37949 F20101123_AABRPD pooput_c_Page_021.pro
70591e376dc856f5b275907c80d26ec6
a219887794d6c68d630f0b69dedc539e0bf9ae0d
798 F20101123_AABSSF pooput_c_Page_115.txt
f9e3caa8eb9743fa2d2eff804eb249e2
1196eb9f24a38c906219119ba7f7582ad4aa2968
1559 F20101123_AABSRR pooput_c_Page_094.txt
cbfd97c9512a74cfcd0313a498351f38
3df0333f51d148a78bed5d268ce0f5022e0ae11c
1114 F20101123_AABSRS pooput_c_Page_095.txt
19e18c29c8bec8ef043d02524e28b4b7
8d81489cdeccf3cb9ab1b6a014d9048f9eb37072
62300 F20101123_AABRPE pooput_c_Page_091.jp2
d14618b0db6c9ff6f285b4c5d1be149d
8c7ca5dd2b8effb29bc1bc6e00cc80847b709474
F20101123_AABSSG pooput_c_Page_116.txt
92c155968ca489199d9c01b2b758524e
60b8e970c5d9ac6ae155b1c1b9e28123cc677e59
1236 F20101123_AABSRT pooput_c_Page_100.txt
ead64b4575076ffbae0643bc60947902
2d765f897c4b0e3256e38f0b65107e5e9310594f
78229 F20101123_AABRPF pooput_c_Page_016.jp2
a70ccf2a202038b119738ed55bd0a090
0b83b2ef412f1e681bf9dba9d065285b23d17917
791 F20101123_AABSSH pooput_c_Page_117.txt
1e13d942b55d0922413fbe3583f16fb3
13d05f79dbb5d7e6dc3080726aef5c7ddfb365c7
1310 F20101123_AABSRU pooput_c_Page_102.txt
97d0220fd5b373900893fe5dc177e0f6
501b6e48088a1fa9ccd7d136dfda34e5cb922640
1053954 F20101123_AABRPG pooput_c_Page_041.tif
11f05e5ab1664961f3455b0bb87ac952
2691d115128088a429bd74ae5d8c6c2815cda1cf
1292 F20101123_AABSSI pooput_c_Page_118.txt
dd6d0545a4418486ffd84de6f4ba74c8
eafed221ef92e6f71bc50077668b28379e20ec8e
699 F20101123_AABSRV pooput_c_Page_104.txt
7e5c08cdbf7f7e169c49e75d88a08053
c7172f5408b608de21c98efbbea719df11477fb2
F20101123_AABRPH pooput_c_Page_086.tif
7021391f7310bf4daee230a78ea8caff
f71645b2f1988c0b75d0ba39c9720c9a6505deb5
1252 F20101123_AABSSJ pooput_c_Page_119.txt
cb8b2a0f9afec86e6350f9653a3d6653
068d77148e8b945b28f1f0e8d76cf9cf41fe3b2a
1287 F20101123_AABSRW pooput_c_Page_105.txt
4a6151d01bf66ed1e6b786bb3b0f6f20
f4cc11502c08337ab345539013cf125bfc0658fa
83702 F20101123_AABRPI pooput_c_Page_069.jp2
723b0438f2a3cd68371812b0bf398103
e090c0d780c5bc839ad220f9fac6e12e36cf6d22
1234 F20101123_AABSSK pooput_c_Page_124.txt
303e4c8708a37080d0c43e03f5adcb58
904a5663549e12b0ec234a1f7264650f843137fb
718 F20101123_AABSRX pooput_c_Page_106.txt
1c62604b261f0c44463b63485616bbb6
6aec1464d03af4f4014efe0eb0a3dacaa119fcf1
13048 F20101123_AABSTA pooput_c_Page_101.QC.jpg
723fe2cac43b45b75a761905d84c4085
cd1b203a4777603e8b934adfa5d66d6f4d5799f3
38697 F20101123_AABRPJ pooput_c_Page_118.jpg
2c82e8afb049126dc5ac3e3d6a9d4e40
0b9e4543f7dfa80b609e7bcb535c41d1f064fc0d
1228 F20101123_AABSSL pooput_c_Page_125.txt
891e62240155e164e81f667cac3d6520
9e8d6f3c4b5863714ea1fff158021b5613f08772
3745 F20101123_AABSTB pooput_c_Page_047thm.jpg
21d7947ac62234535178ae195047981b
7a6d1f9968bc07ce2cf7c054e0b71c70781f263c
64093 F20101123_AABRPK pooput_c_Page_004.pro
a71ecc3a13015a5d65a4ce884ef92a6f
8c84c9f7e33e217cf26765ae4d39241549a18cd2
1294 F20101123_AABSSM pooput_c_Page_126.txt
193127c0509a968eb1bf3c47d1312061
d179f8a4d5babdfc9eb6526b50de6dc57093f6fa
22669 F20101123_AABROW pooput_c_Page_001.jpg
f726e4daa5ce70ccbc28b723e2f94c49
8de8824fb30418f55c706bad8a2534a22b55dafa
1167 F20101123_AABSRY pooput_c_Page_107.txt
d5866f53f0bacff7452bdf8b5b3b5823
c70541922afbdb408b3e00da522e1396b32917a8
5813 F20101123_AABSTC pooput_c_Page_027thm.jpg
2936bd21758dde58b01194b7c586f3d2
36a33321bc16336968a4ed6cfe1d4f1692980343
23305 F20101123_AABRQA pooput_c_Page_072.pro
f1cc3730cab2755d1cfef8389ec851a3
be60977f00edca7cd82c3a83e539ac43cf285392
46526 F20101123_AABRPL pooput_c_Page_009.pro
1fed6e1daf91b674863d3c572a835ce6
683bb5f08a52626bcbc4940b536a316a51242b18
1022 F20101123_AABSSN pooput_c_Page_127.txt
d92e64f5b7f60b2c982f362f5038f216
037facba990cd3121d53ed1ecc42c8ae36018e1c
331798 F20101123_AABROX pooput_c_Page_090.jp2
f1687f652d5e7b93d59503831da32d0c
9d9e2c2e37293a29337bd703bb2ef398d6db5111
1155 F20101123_AABSRZ pooput_c_Page_108.txt
a99a2da3b3e942b5d28c0646bc85fcb6
e6a0795384135e2064c1097d7d6187a4cb7f3c4c
1494 F20101123_AABSTD pooput_c_Page_002thm.jpg
98d801ce05b319f60c154546c38db389
0e68ab2acb17e34a5408e9a598a3331e06f07bef
1625 F20101123_AABRQB pooput_c_Page_044.txt
a6c05d777945ba41fd46f6de8ffca630
55ce3d7501bd5f35280d0418634de285710147e5
38959 F20101123_AABRPM pooput_c_Page_033.pro
d9e084615dd38afe5f8ea6da83d834dd
4439a049720eebe3e20d175da943b023385b7ba6
1171 F20101123_AABSSO pooput_c_Page_128.txt
9d8a4caf8a0519095ad17c269e6ac025
e106f9105fc0bb2b55a97e89760f7f22d9efc52c
F20101123_AABROY pooput_c_Page_130.txt
f387cb1a6296bb34d45ba6c707faf966
de090961f08a2457e2ce940f08e8f8cf519a7758
12336 F20101123_AABSTE pooput_c_Page_103.QC.jpg
75985ffcdfdbc7fab17ca0257f782dcb
e44205462e745673cd122091e1dbd4161d8c214f
5173 F20101123_AABRQC pooput_c_Page_081thm.jpg
8507225c27c7bedc4ba27116117c497f
91a83a6784ce77501172cbd7f54c66bc34d577bc
49016 F20101123_AABRPN pooput_c_Page_092.jpg
946e1feb218e074c60786b135095d3d7
6a6e89e5d5636d1632ed16c885eff03e166e4174
1217 F20101123_AABSSP pooput_c_Page_129.txt
689229b9be5cca0eb6ef8719b60876d9
85c2f921bdfeef4fe00fb220f9a7d42a56418cde
3088 F20101123_AABROZ pooput_c_Page_111thm.jpg
476c8813ebd7b4889c5c709cb012fa68
1be2c226cc5a50779f049e219de79e1b8d1b6f92
5358 F20101123_AABSTF pooput_c_Page_139thm.jpg
9a02cbdcf8a993790167a3162c7923f7
1c68ac7fc85f3f24181f10574ab2d8fad6c4bde8
39529 F20101123_AABRQD pooput_c_Page_089.jp2
e0f4cc6e0cc758fa0fc52d60a589de2b
4b23d06569e53238a5582c416aef5c99f037c3ce
91127 F20101123_AABRPO pooput_c_Page_006.pro
96ee6e02edbc9ef149f8149dc4434fd3
f76a1e7f4573dceb1adc148991b110c19725bb0d
1000 F20101123_AABSSQ pooput_c_Page_131.txt
3f2c76fcb14c0077fc246a8fff91b923
d2e06b4566c0ac7d23159bfb2d5bcefe159a2c8b
2275 F20101123_AABSTG pooput_c_Page_001thm.jpg
76b861d4e1f788a11d71aaa8cd76cd1b
48aa7d6ca65f513e1ad1a032879fc3a7790029c9
35079 F20101123_AABRQE pooput_c_Page_103.jp2
d46b23cbad9948fbc61f8cada452df07
53fb78a2e47b698efac548bfcdc9922e8c7fd92e
6462 F20101123_AABRPP pooput_c_Page_053thm.jpg
3d263c735b12c588b66e6cef383dc4db
06e670fee968c2ff7f19b9af330994485b344260
1560 F20101123_AABSSR pooput_c_Page_132.txt
d21c80998e49aa2a7142eb933853c239
98644fecaa0202ae7f45cdb08ec8f8a9519292a8
19504 F20101123_AABRPQ pooput_c_Page_062.QC.jpg
4b57ff5db7b38d6fa6a2a46a21f05b7c
062dcb650e12d8848da714e87d4709f0a8084d89
1575 F20101123_AABSSS pooput_c_Page_133.txt
0c655c1835306ac2316d9b6185eaf9cc
154e04223ac71a9e8dfbf267ae3e8633cf45aa53
4952 F20101123_AABSTH pooput_c_Page_082thm.jpg
44bf89342ef2aeec47741cca700e7f62
15ef635c2f24735f8d4a3be0e325320bcf097776
17089 F20101123_AABRQF pooput_c_Page_119.pro
21e33fbd79ee7f0c589525190af11eae
3902b4e4626c0658feba48505c4f29818d734ab4
5856 F20101123_AABRPR pooput_c_Page_055thm.jpg
81ac5b7c19f5153d6e798c6b340073a1
eda9f7998af1caa87aa7ea67b46266fca49a98dc
2130 F20101123_AABSST pooput_c_Page_135.txt
4a66cb2dc1e4d537d5a5f6741ec9c163
44b0927b4fee466d172a6e39c8f02115c5684bfb
3700 F20101123_AABSTI pooput_c_Page_114thm.jpg
262a16c356fddc44bce95a9c705a1520
169886d457faf051e2ec86e8daec669d4daa49ea
F20101123_AABRQG pooput_c_Page_072.tif
5cfa6e64f7f793d84a97f75f826a97c3
a01cf37e8687749d92dd7a714e26573b4e01d8a4
1834 F20101123_AABRPS pooput_c_Page_027.txt
c4573b3caeec2dc32fddfa9cb59cd1fc
1e3900ddfb9bfa05e2aa5b3d30658399874662ef
2205 F20101123_AABSSU pooput_c_Page_136.txt
95fc74db8fd4c260b99a543e63783805
58bdb67f705e2d973781140e9784aa6afe71908b
16534 F20101123_AABSTJ pooput_c_Page_071.QC.jpg
fc5b3737216d2a5a94128503663e81fc
0cb9b70101eabfcd19b5487caab49dcf99c300cb
F20101123_AABRQH pooput_c_Page_099.tif
0029ce5ff3e756a5b25a3d47858fb474
991bb42d7e32843efbfb6ca647d020555a92f972
5556 F20101123_AABRPT pooput_c_Page_036thm.jpg
9c0ef072cfec363d6b8a5fe3b740f187
1a8f997ebcfd24bd8678ad892bcb8590f8a74477
1910 F20101123_AABSSV pooput_c_Page_137.txt
515c4c2ad77a8e67cc57d8d9227c1ff7
cb636f8a6de01f39780e3330059132c5aad2216d
6090 F20101123_AABSTK pooput_c_Page_039thm.jpg
341bb7a10a52c8daa0e82188e6fcc3a8
7c6501308287067ef88bdff31f18b3be4fe3a58c
10106 F20101123_AABRQI pooput_c_Page_017.QC.jpg
623baa681ec15a12bb67f2c90f062858
e688ec72ce5f6d1911791cbfce3c4500fad54bca
49284 F20101123_AABRPU pooput_c_Page_074.jpg
079dca27364da998e5952949999925bd
805a4d613527e5ec0f6409baafdc12b11b2b75a4
626 F20101123_AABSSW pooput_c_Page_138.txt
99b7a79093904def765512437e13640c
d3ba78d6c89e0d6ccb85648f2b9812ae70407557
8529 F20101123_AABSUA pooput_c_Page_121.QC.jpg
f8093f19c8c32979188cc94ff2339a5e
471e172c919ac82983e8c28ac916da9f7c3a9e55
19397 F20101123_AABSTL pooput_c_Page_008.QC.jpg
e29f6cf5f3fee80d2033277a163a0475
d78c36572e5561f09bdcb2b181732a0d7e683eb8
4476 F20101123_AABRQJ pooput_c_Page_076thm.jpg
31dccdf8ad42dcca9c68306ac8dd2c8d
9ef7049de058b87e48041bbdc3ab3a0b7fdc8411
3898 F20101123_AABRPV pooput_c_Page_103thm.jpg
5d90940777080bd87dd216a2afc3b5aa
f872b607590ae074a1ba4ff22e08f8f782a7a8c3
713667 F20101123_AABSSX pooput_c.pdf
b5ce4142a79d7b2568d88e3b27f685fe
48acb9c2f1f119b0190d7977ee1326752de5e8fc
4061 F20101123_AABSUB pooput_c_Page_126thm.jpg
7765ac5bb721acafb3bebac11f5aa1d6
0c34a31c9eacc4ca5bed35d422d35a1aa55db99e
17976 F20101123_AABSTM pooput_c_Page_032.QC.jpg
4897c01c166ad98c064dc4aeacdaa1d2
b0e9238a421da652f36699cb08e25aa659adc5a3
40802 F20101123_AABRQK pooput_c_Page_116.jpg
83e2df04514956944a91ac0078d6bf17
a6c18ae06805ce13103b43425815b65cafc004ba
F20101123_AABRPW pooput_c_Page_098.tif
182a5c1dced298ae4ba1ba63c3179252
d703c363953ed94ad57e64dd7548a9fb7c0a8851
17777 F20101123_AABSSY pooput_c_Page_024.QC.jpg
c87f1831def697adc8f250e3134b9ede
b8c205d66cdc35df3f2db5ad25a731174794e1c7
14100 F20101123_AABSUC pooput_c_Page_070.QC.jpg
9725e96550edae8d1380cc28248692a4
5eb057937a681c3e10589d54266c2a592efeb2b1
20347 F20101123_AABSTN pooput_c_Page_039.QC.jpg
7cc4d3b146a880d0fce631bd372dc9b1
f230cff37de237479609c950301db578b09168cc
2444 F20101123_AABRQL pooput_c_Page_007thm.jpg
c905fd6937f5870454f77dcc416a94b5
36471e58521cdf94bf5a1abdd5605e83e785b5e8
2805 F20101123_AABRPX pooput_c_Page_004.txt
b87513e4c3069c155214d1ea077bcb1c
4b2bdaaccca4b638ce55d43c6f213175c9b75a40
5297 F20101123_AABSSZ pooput_c_Page_024thm.jpg
580cef579bb31edc141c51fbe7cdc683
3478f3a5deeb14911d0eb8074e00c9e7157ac424
6438 F20101123_AABRRA pooput_c_Page_011thm.jpg
57335fc9ff7e30505df1be05e14b9752
841f63cebaef37800fb6f996d1da439eeb5c0f27
6508 F20101123_AABSUD pooput_c_Page_041.QC.jpg
32031ff33863e385ff0716333bf35e97
144a11d75d14a5896ba78895f323546d6397b7c1
5099 F20101123_AABSTO pooput_c_Page_068.QC.jpg
880a20c4f9750a3158d6a6c528e1ed3a
ae7727ef59c7016473c9b2931a60149db34030eb
14605 F20101123_AABRQM pooput_c_Page_068.jpg
f5096c6c614fc0dd68c2cdb745c09dcb
9a49dd30093b6b2508e30080feb3baa8ac7055b3
97110 F20101123_AABRPY pooput_c_Page_051.jp2
06ecd80517b304eb04a44012983b0ca3
f7eecd147a792033829d63f528e5d378321fc71e
F20101123_AABRRB pooput_c_Page_063.tif
424545f4caa2a43a52214c5e109179af
89252bf0a118b2db40b0ab419e7729fb59739e94
17649 F20101123_AABSUE pooput_c_Page_094.QC.jpg
43c385c2097d472c97a56658dc7b53a7
644729d885a4b166a6e8189bb3d685ad3602e38d
18665 F20101123_AABSTP pooput_c_Page_052.QC.jpg
7e2ea3b5d0c8bea5182889ca62cef73b
5f5b07952d35cb813d4d80b18aab64f869099ba7
51004 F20101123_AABRQN pooput_c_Page_091.jpg
1c7af48b904ca9ae94e0fb10ba40502b
bf54300eb28ba71301833c43aada1a573224640f
25271604 F20101123_AABRPZ pooput_c_Page_018.tif
77f073db0760f5ed89c522d2381d42b3
a9387c263040dd7eb735dc8780c8f338708ba3e4
39348 F20101123_AABRRC pooput_c_Page_069.pro
9d02973f6580ba6e31bd2cd1fde64527
b35106df6932b774bda8b356d8606e06ecf28c5a
14248 F20101123_AABSUF pooput_c_Page_029.QC.jpg
210417b5e3a89fc0c5a661d413693b3a
6462c19ad84b49014fb860b4ed4329a00c14e487
12240 F20101123_AABSTQ pooput_c_Page_122.QC.jpg
4f3411dff983c3bdb4ca373006a8a377
a03c6a5ac7285acda0156faea64af258ef59954e
6217 F20101123_AABRQO pooput_c_Page_078thm.jpg
923c1fb54405b9d8cd858fb07548dc9c
0f4428c19f836953c76ba64507689420954bc606
1244 F20101123_AABRRD pooput_c_Page_123.txt
21cf63b6f3a09a66f5f77e0324e0885e
6321104eb548cad2aa8fc71880134471dbcc6e75
3334 F20101123_AABTAA pooput_c_Page_117thm.jpg
6c570d1d4e1f4c3bca14d77982cd8294
43e7e6d66927fdb5e7b896109f47d5787c99d82b
21407 F20101123_AABSUG pooput_c_Page_080.QC.jpg
025185f1fbb689f72bee37371b532439
f19df9e2ffece03c3488125a210b64287eafd489
18989 F20101123_AABSTR pooput_c_Page_033.QC.jpg
aa32cb59c3e657b512a47023dcbf2c4e
8274bdc54071473f3ec5fb5dfe32e67f37e73826
26547 F20101123_AABRQP pooput_c_Page_106.jpg
0028942335f2a2cb682bd4331f1dec36
94cd0186fc62c70d56ffb37b68c36a4b0bde7dc4
5277 F20101123_AABRRE pooput_c_Page_064thm.jpg
4e4507ed05529abcb56c4c3a19d1a89c
370a8df886742ac1afdb42ea11e4a39a5483069a
13069 F20101123_AABTAB pooput_c_Page_118.QC.jpg
1bdd134700dd55ddfc04caa0ae193374
72c06fdd9da94e45b28eec679fd2652c434413f4
18274 F20101123_AABSUH pooput_c_Page_088.QC.jpg
836e11207348faade6d3c2b963b5dcd3
1aa428ac2ebd2192bee894bf4d13ad38d2ce7df1
3390 F20101123_AABSTS pooput_c_Page_108thm.jpg
48998d19315f156fe72a29837a5b0045
6b99c023d86d3074a2597499fad92a1385fc9b9e
1839 F20101123_AABRQQ pooput_c_Page_057.txt
17fa52eb511a05778a734433eca88d1e
1c2f1b1dd3cc5840362e25cc2344dcf03074d9d4
31641 F20101123_AABRRF pooput_c_Page_030.pro
d096f05a30cd5e365315fb79818a45c3
a91fc72fe7fffde148941fccb49d7de2a31aee26
3382 F20101123_AABTAC pooput_c_Page_123thm.jpg
36080cea52b6cdb5c4c0156942f321ef
c1de03b066638ffa3264e1bf584e596943fc3f7d
21072 F20101123_AABSTT pooput_c_Page_073.QC.jpg
128179edb66886443557bd1d036f176d
b3aea1b11211d286f2f498d2850094579261a9d1
82832 F20101123_AABRQR pooput_c_Page_033.jp2
019a722ac82a5279fab52c9cf2739995
520b5c681fc02acef5b94231e7418e5a922c33cb
3237 F20101123_AABTAD pooput_c_Page_127thm.jpg
92954ad00f2460f20cf7cf0baf9de047
7c962a361c3b5a5ea2d22bce58afd3e2c46ab7de
17374 F20101123_AABSUI pooput_c_Page_030.QC.jpg
923c806236b40791b8c20dace7a2adb8
ceedfe1aac14f66c49437adeb6ea12511e108640
3322 F20101123_AABSTU pooput_c_Page_119thm.jpg
c7e35cb0522a26ceee73f9a8c3e921d4
4195f8f6add0fb4a27c7206cccf002c5e78fa387
38079 F20101123_AABRQS pooput_c_Page_045.jpg
e9c5f8fde442bdd866cdbfd73fc593cc
f92bfadd6d1d7e6ea8092b58f8d1a134e6ed37aa
15498 F20101123_AABRRG pooput_c_Page_044.QC.jpg
49506e63e51abee6dc73eaab95584172
90c0c9ff1d39a8e779c2059e3d1f8650eaf4eb7c
13005 F20101123_AABTAE pooput_c_Page_130.QC.jpg
72dc39ca5dc96a4283a7d3c63a206511
1ba889cc6fa64401e2aac2e5f2a93332c84e65ba
20792 F20101123_AABSUJ pooput_c_Page_066.QC.jpg
ed88e9d838484db055383c3f60dfca5e
9155ada491e35836bb76efc39d1e429ec38a1a4b
8519 F20101123_AABSTV pooput_c_Page_129.QC.jpg
024b9f49503692535d1f0c7096a72708
32f47ff0931470bc71d9b155f4ba90eb61e94581
17133 F20101123_AABRQT pooput_c_Page_081.QC.jpg
cb80888f70a94a248b66aff4091c768e
3c7998696fd9bc8d5cc6ac0d149922b264509210
F20101123_AABRRH pooput_c_Page_010.tif
873c5179774c0528111fc8fd9ebf7018
acefedd17125664743fc660d6d043203a60a8751
18966 F20101123_AABTAF pooput_c_Page_132.QC.jpg
889406b725b7e78f5f723e464a08b65b
f7bab5e4ffcc252e71bca6745b47b2178944d275
3856 F20101123_AABSUK pooput_c_Page_120thm.jpg
bd76d2bc861db3d9fbf3b897404d4c59
697c327c4162b4ef010ede1875037119ebeb7859
26156 F20101123_AABSTW pooput_c_Page_005.QC.jpg
ccf961c83adbcc9b522fefe0e8c77025
273eb50491ded66dc06038ca8ee281157ad59b42
59204 F20101123_AABRQU pooput_c_Page_072.jp2
8b94c3a94f594dd440fd2d8b98ba6180
05d6e51136623eb52808849634460b36460a724d
F20101123_AABRRI pooput_c_Page_093.tif
32905f2a37d4f8ae328e6887e1ba03d9
c413835e27a6bde8be0677e6b5774604de76bb00
24795 F20101123_AABTAG pooput_c_Page_134.QC.jpg
16bf60bcb45fc6d459317b9f93f8b631
acb112266b2e021e31099ae2fefcccef09ea28f7
23043 F20101123_AABSVA pooput_c_Page_014.QC.jpg
c3a9983aad27096e0d22fe64b86a17d9
038671bba011d89e58b8a522900f9f831b7391fe
20044 F20101123_AABSUL pooput_c_Page_097.QC.jpg
dd3538b402e557fd7b025192e7daf5ef
efb4e874a089118e302096d7ec7f73678790ea4f
14765 F20101123_AABSTX pooput_c_Page_023.QC.jpg
5b3e4a4192416239ff12ba5071aaa558
307a33b3c9c8f9ec4c4ef64df7ab28c88220ec5c
1179 F20101123_AABRQV pooput_c_Page_120.txt
d431652b6cf244dd13afa610dd95547e
b0141acd0598e7c7eedfc3321644765beebd9c32
13123 F20101123_AABRRJ pooput_c_Page_126.QC.jpg
43cd8f48a1166ab036bea2004208a233
25a8069810456d972c5cd1f21944dccbca28bd57
6610 F20101123_AABTAH pooput_c_Page_134thm.jpg
a373861e75a08f16c70e0ee5bf77aafc
44d3dfc17e0705e14b0f74db1d573f522e08237b
F20101123_AABSVB pooput_c_Page_099.QC.jpg
67ec2b0b53d240390c4f20979680fad1
7d3ef5b2773717fcdebae6cc1750fc7732c3eef8
14344 F20101123_AABSUM pooput_c_Page_076.QC.jpg
e7b6c19dab0e18aeb538bf481ebcfe96
3d203bff9066c47c938755db9bca1c961ea22d97
3359 F20101123_AABSTY pooput_c_Page_106thm.jpg
31b6da4f8bb4df3270cf586228e9de6a
c787d305281a23bbe7baa0493175998336f7cbd4
40804 F20101123_AABRQW pooput_c_Page_038.pro
1c92304deccab41ea366c47eb0837e2f
a5bef6cf9edcae96fcc253f64c5fb92d5ff14558
17058 F20101123_AABRRK pooput_c_Page_103.pro
7b01e7cb58f98f1a12c0fcdb3530e0d9
5858d51bf03e1eac4f092c8087995f8a72631f90
22935 F20101123_AABTAI pooput_c_Page_137.QC.jpg
e898978d9ae06a203d739d0e6d54a6fe
346fc3c5855a5c66655f983d734ddc81e3755de4
3195 F20101123_AABSVC pooput_c_Page_104thm.jpg
046a4a9c2b0e9e37b362906da62588da
215e0e8b1b6a45b84ec906ef396c4d2032a1686c
15268 F20101123_AABSUN pooput_c_Page_092.QC.jpg
c97ec81f6d534ebb451214dfa02586eb
c9cd834198116a5bd53c0e09466516aa97096b3d
4983 F20101123_AABSTZ pooput_c_Page_094thm.jpg
0f7c6f6f505afe0fab615bf79fc47673
983f0a95b91836d5c9be1ba38afc2578b2c6de55
11322 F20101123_AABRQX pooput_c_Page_047.pro
a3fb2d00ecbc5e5661dc6a5c4ed4983d
9604152325e75ddb61cf26235c5a231621674003
5233 F20101123_AABRSA pooput_c_Page_086thm.jpg
05141eb72d37347c6b5d6c8b9e3d8047
a4bbe2be53e791b486d3e605fa27511dac7e7ec8
6011 F20101123_AABRRL pooput_c_Page_022thm.jpg
6f0b298326387cec45b49e0470b8869a
711b4e4b58ae14d385c89c519a73ba21d05ed978
6020 F20101123_AABTAJ pooput_c_Page_137thm.jpg
f2e3d9754fc2bc61a3ce9189c3961471
6871cbbe6acbdaf763eeba6f8985fb6b272baed8
3080 F20101123_AABSVD pooput_c_Page_113thm.jpg
f4b5d56957c405ae1a39dcced7c5492e
367459c47ed2c68a650049d2611291ac4e3c5da0
6037 F20101123_AABSUO pooput_c_Page_080thm.jpg
5983e8fe12aa9831a782a0232c1f500e
7a5706732377266ff32d4be64a1abf22c46b9c4c
3864 F20101123_AABRQY pooput_c_Page_128thm.jpg
4a20209a6c54a63507e68296c9905682
a94ad67f49480b58fbc0a95161a07e4979c8b98c
38956 F20101123_AABRSB pooput_c_Page_101.jpg
57b6dae62ebde1e38cec2f98e6862fe3
9007011724931876371b3fa905c05f7e394e3c70
F20101123_AABRRM pooput_c_Page_139.txt
3979b015080ec256a7840e55f706df0a
9b4a582ce9b16578ae60950da4ba0eb9575b7401
8592 F20101123_AABTAK pooput_c_Page_138.QC.jpg
52517eb91a0a183453d784a9b2cf0dd9
4bbe0dbebeafd0a7072a5b5e9dedd1905cc9b2c2
11988 F20101123_AABSVE pooput_c_Page_047.QC.jpg
12f9e40a4038e536dd6e75424d78aaff
6a74870c8130b5e74d659eb04f8d1acce8307805
9220 F20101123_AABSUP pooput_c_Page_100.QC.jpg
30f2043e2d0720922397b549c8f2383c
73714e32684cf9e371a1dbfb54bdf5b0d636e7a2
425509 F20101123_AABRQZ pooput_c_Page_111.jp2
f8680ba1cd0710b0e2e33dfbb9f2373d
0db28c4c2145a0fd37f201a74fa156d4f804b4c1
83255 F20101123_AABRSC pooput_c_Page_054.jp2
c35ce5461ee8358fc55fdaaab3d3677f
cf3f85747e04541d66cf186b73a76eb1fdb72ecb
9640 F20101123_AABRRN pooput_c_Page_104.pro
ad666e5d962fc2db8d340098bed21e87
ca8efd57de72eb505e07d83bb8113dbab9782316
18494 F20101123_AABTAL pooput_c_Page_139.QC.jpg
75f3cd3e395c8f7e55db28f48635c2c2
e20ecc29094983e2e74db284503634583f975c77
19883 F20101123_AABSVF pooput_c_Page_022.QC.jpg
de97b5a189085da658d1d7c49b8507bd
951c947431c200fb6838652e40f6f1bb1a4ff043
11888 F20101123_AABSUQ pooput_c_Page_063.QC.jpg
4662023ca085fb37a0f79e5c61c30add
fbc36567f761644cf2418e7494ce386e182ac03b
3912 F20101123_AABRSD pooput_c_Page_095thm.jpg
6fa2dda55c8812fd5a70d1d2e9bf19b8
a4d985fe817eae8d37c0e05fd7453f8c8c272bc6
5135 F20101123_AABRRO pooput_c_Page_020thm.jpg
d2e71c9f25afa9337d21b2b0e47eb763
a341fcc137a8976ae092c3615896d42e32784f93
F20101123_AABSVG pooput_c_Page_004thm.jpg
994b2fc075adeca902233627c6b1c724
4cfa38fd7251949887d111a23cf467006ba346d4
15255 F20101123_AABSUR pooput_c_Page_020.QC.jpg
070b2e8c6aad9b4552bfda454fcdc400
49363b6687994eac5f0214334a2339bf1e93ceb3
367 F20101123_AABRSE pooput_c_Page_041.txt
f4fddccf415d6536f0a6107c538adf5f
8f2d2f0ff8a15cb4b25adea62bddfe3e404e10ba
1850 F20101123_AABRRP pooput_c_Page_009.txt
43a1e27751139debc7db4f4e04ac4789
c6e8bff38d4312ea76a966f5918e4148c943e632
8554 F20101123_AABSVH pooput_c_Page_117.QC.jpg
c8b54c6c0cf60d94bea87746e947bbfd
baabb091bb3e7afa1e458fe5c5a4c65431657c61
3941 F20101123_AABSUS pooput_c_Page_124thm.jpg
fc3d8de6e5dd77704d55db71e13cb265
1962bc752f18630865ed9868095384971c0b9499
53003 F20101123_AABRSF pooput_c_Page_021.jpg
2d47af3b16bf7129e3513582651ea243
51c5028b7351df4252fecfed0cbb604031fb7f2c
1016 F20101123_AABRRQ pooput_c_Page_063.txt
a7a6e5c7ab68f3b72b2f74e1714fed99
2ad103c6eca780c8a0db5f3da57da7c5aa75caff
14705 F20101123_AABSVI pooput_c_Page_072.QC.jpg
270cdb2629919f2391ae4bf2f5acf38b
c7b133efc511aaba4364186493a69b3a14f9636d
3453 F20101123_AABSUT pooput_c_Page_115thm.jpg
ba1240af1adb6ef69d2538fc0239121e
dc96467ed3a4449ce545d2b906ce41930c043e5c
35381 F20101123_AABRSG pooput_c_Page_086.pro
321fbed12a75953ec40717065dc7f487
e516fbee060e0ab97831b96a7174e04e8ab73661
91146 F20101123_AABRRR pooput_c_Page_067.jp2
369dd5405ae47dbea6c3556b2288868b
1a695fb0ece3fcf18b638e25d051e7ba33a10cb0
5667 F20101123_AABSUU pooput_c_Page_013thm.jpg
bc4d9c51515c0a98c5bf628cbf24c5f7
c8d069a448929d8931a39622e43a35426368f2c0
17694 F20101123_AABRRS pooput_c_Page_048.QC.jpg
251ee99a0916eb45d4ffac109c1125ad
068c569c43c5b9e57be3f49f068ddd42abed8798
8908 F20101123_AABSVJ pooput_c_Page_079.QC.jpg
56583608895ec37d811cd080c9c0459c
c32f3235cd8a4d32ed2275969dc51b7d4a658a7f
18782 F20101123_AABSUV pooput_c_Page_069.QC.jpg
3ad47e0c1709f0acf98fe62cfc119855
7e9d126ccbb3fb9018526d1aa19757557bce4995
8561 F20101123_AABRSH pooput_c_Page_125.QC.jpg
f4a6f7b714ccbc10d1dc689e191078f1
01b8890dc4b5e7c4fa3227f3d3e6ef5c354423ba
22720 F20101123_AABRRT pooput_c_Page_053.QC.jpg
0cc0d6725b1856e0d25eb2e5e8341832
212da921db2cdeaa39cf12c0d06fc3f3e4645646
6340 F20101123_AABSVK pooput_c_Page_035thm.jpg
d1f6577f1e272d8c8dc0a50dba46bd1e
f3d6b96be8e6a3d4e333b774d8aff6678987de78
4020 F20101123_AABSUW pooput_c_Page_118thm.jpg
09f0d848af3eda660a4de5cabfa765c1
d8bb54ea16b1fbfe7aafcb1414469a5b7210628f
F20101123_AABRSI pooput_c_Page_062.tif
851a2790ca1854fb6840d8bed549c20e
0db55a56f2fdaeb254a75d4109db4c8900c32d78
45954 F20101123_AABRRU pooput_c_Page_057.pro
c4575f932cac2dbacf23e957ca9cb58e
558aa9e114c69ce9cbda3980b4c47461ff02af1b
6460 F20101123_AABSWA pooput_c_Page_136thm.jpg
6bb0edbab9a6206bbaec352e5006f77f
8ead9d5b9a05e5f9b74384171247266c01d3c3b4
1655 F20101123_AABSVL pooput_c_Page_015thm.jpg
dabb24b8f890224b3b581849d36e2e22
fc6045765d3c407c94953171df424e883d9cf458
5635 F20101123_AABSUX pooput_c_Page_056thm.jpg
0dd7d13c20fe30f60fc0de0bc720cad2
9aa5c2951246cf5062ca4461e7d840ccb2239fab
27043 F20101123_AABRSJ pooput_c_Page_131.jpg
a953b89dde14d5bfc55b0171d1390bd8
ff4d2fe9e97b0b2c63ad2567a2671c272d5376f9
6228 F20101123_AABRRV pooput_c_Page_067thm.jpg
261e7dbe495d6519ab78c6d756a4aadb
9943c2c97595e6e783d1a7b8370364e3bd603976
23460 F20101123_AABSWB pooput_c_Page_051.QC.jpg
cf7a5483d83a3204a33e8cb74a41ad8a
ed56d632fe8d7946a976589ac6c9175b7608f3ab
6030 F20101123_AABSVM pooput_c_Page_077thm.jpg
ca3f99dfa49b34761178ddcc797a774b
9f026d3a7464c2cbba20d8ba269d3be660718393
5032 F20101123_AABSUY pooput_c_Page_075thm.jpg
d898e7ab5a62f4282375f6bf2f30f348
e20bae1b0bb801f865f3e2e4ef2abdce41a976e0
76580 F20101123_AABRSK pooput_c_Page_109.jp2
f417d229dfc7399a2dbaa00a83085f4e
bd42cf380338eedd65aad3d7c08c37d78f7953e7
29879 F20101123_AABRRW pooput_c_Page_074.pro
4522e44c9ed795baa1a369011a7212db
6c72008bea1360d70e21fc905102f493314f7111
5393 F20101123_AABSWC pooput_c_Page_059thm.jpg
217505ed8fabfd93f1f01a1c728ce865
6ba7953ee698cb5df7b00fe542d914db68d5753a
25063 F20101123_AABSVN pooput_c_Page_006.QC.jpg
1d420276b32102a360cbf848fc7d4281
1abb7a4f7dee8200982a2be4c7b36b7f3e9e0eb7
20850 F20101123_AABSUZ pooput_c_Page_055.QC.jpg
aef1a55469343e072651f9ed927ca254
519dc520762253d87e84e994a70302b10290d75f
F20101123_AABRTA pooput_c_Page_080.tif
8f15ac6115f0d117ce6fb86aceaa992f
d25f9679394ac7a5872dadf680fa447ae87549fa
F20101123_AABRSL pooput_c_Page_022.tif
a2e9f9ee10ce3a01b1d52cb9addbd67f
de67e6dfd64323163b77a6a7de0924c169d19cc2
14740 F20101123_AABRRX pooput_c_Page_049.QC.jpg
434f355f1484da00082eebf89b173b1a
330dde51dc3a5f85f2d0f0d6c4f28c9e6929f0de
3597 F20101123_AABSWD pooput_c_Page_002.QC.jpg
cf71510bce22f2961776f1e6ec76fa34
30d5a41678ae628f4f9c1d89b680a88fc2896bc3
6134 F20101123_AABSVO pooput_c_Page_073thm.jpg
23dc14bd189f463bb2ca0d80575d2219
04b4e1224dffc0da616ece1b1824a55f612e64a3
F20101123_AABRTB pooput_c_Page_108.tif
54252f897cc9f3ec1b95431cd70502e0
546e90675a9da36e87b13e93438cc817b0b21bc9
23175 F20101123_AABRSM pooput_c_Page_037.QC.jpg
216fb00c74a631698d52dea54348f5fb
a5f1f2b944542fcb7f100e1e6a96e66733cdfb2c
713 F20101123_AABRRY pooput_c_Page_093.txt
918860f7e97d66a217bf761c899ef663
8a518ad1902f90efda460c342341e233ab192239
19456 F20101123_AABSWE pooput_c_Page_036.QC.jpg
fe2c40d3f67d756d05992761616cc11e
4ef467d3f1a5f23ef3f4dc13c24d22f2ec4c4672
4422 F20101123_AABSVP pooput_c_Page_061thm.jpg
860ac95450c2151dbb2faefbf9f62b79
fbafdb2bd9dd1b8b03b32442beee44ee3e8b7aba
976 F20101123_AABRTC pooput_c_Page_047.txt
20ae36e5319acf8221dec0fd08a0022e
60c51cb4c12ca247332360ab12e799b07c7d4ec1
25265604 F20101123_AABRSN pooput_c_Page_090.tif
ecb18497887ed08e620a9dc54e2e90ab
2dc60c8478ca8db57474d3ecd2d4bc6fb6ea9f5f
45693 F20101123_AABRRZ pooput_c_Page_053.pro
a6199d14429f3adc8e38d2f76c8adde6
0d07a26762d7591d07f1acf493ea3e1390fd2c2c
4136 F20101123_AABSWF pooput_c_Page_116thm.jpg
dcbbcd84d1dd47f22a768326637af6c0
5f065b08e9968b45bfb89f335e759879c76bf55e
18438 F20101123_AABSVQ pooput_c_Page_034.QC.jpg
b4ab5ae6fbf71be8749240222f857a93
03a5d5ec71a2e23ceeeeae8ec54f4f702d7250d1
37992 F20101123_AABRTD pooput_c_Page_126.jp2
d3d954f5442155d2e0f7d316e222f4e0
56db8de078bafc8adc39b4902a1bcaa9f0934066
77846 F20101123_AABRSO pooput_c_Page_136.jpg
c3719976adde907263965413df5036a6
7f37db58bfd1b94e7a16e4b12739f4f0f3273424
15029 F20101123_AABSWG pooput_c_Page_083.QC.jpg
f70f15c6bb3f47fbb20867a08570b598
11ece34c41042b0c1c12c827751574bd909272fc
4023 F20101123_AABSVR pooput_c_Page_130thm.jpg
d48043acf66f8ce64ff9cd1af4e67456
e88a9443efb8f821f1d6750076edcd1ecbb2a8d6
19915 F20101123_AABRTE pooput_c_Page_003.QC.jpg
9a5c1d75f226ffeb3546ee6aedfaaade
8e402563ea7c36365f3d571218b840e1bd7b9902
37742 F20101123_AABRSP pooput_c_Page_124.jpg
937ee220f3ace4035aa9d15cf4c5d171
d08582ed0b9503eeae01cdface3ed93b96b16b43
12845 F20101123_AABSWH pooput_c_Page_105.QC.jpg
72261becfb7fcdd9872ad007b4383f8d
567657c93faf1b6c497acc5b592139f03fa318c5
12152 F20101123_AABSVS pooput_c_Page_128.QC.jpg
e747eef56526f63308d5a75408ec83a0
0921c70ccd734d3d3f93b7651055b1f4ca9964a3
16681 F20101123_AABRTF pooput_c_Page_120.pro
2bc86e13454c91c4c9fafe06752b0a04
ce2f14944474de94734c0167e63e778945bc342d
44583 F20101123_AABRSQ pooput_c_Page_044.jpg
258dd72d166981a1ce9669adef292a80
6387b2b6d5e598d239973acd1405c5631085bdb3
2643 F20101123_AABSWI pooput_c_Page_138thm.jpg
95ed136a30074593b72ddae2c60f3ae2
8c13310a1d3785a2e8d2af10082f6c35af6749cf
4880 F20101123_AABSVT pooput_c_Page_074thm.jpg
a8ce3cb3633ee3d312f6ea1620dae0bd
112f3397339835eff5a5acb92b749163a653587d
F20101123_AABRTG pooput_c_Page_127.tif
171a2c0cdb90644e6998c935b64837da
8d9c0d785f0d6ddd688a74ef938420aa1683bb1f
3368 F20101123_AABRSR pooput_c_Page_100thm.jpg
8b1c531f54741cdba577448476ffff5c
27600cb5a75ca80bd35c6a5599c14eb0f6efc377
2256 F20101123_AABSWJ pooput_c_Page_041thm.jpg
46d4327958a83b0599ef4759c7dc9f18
07d735bfdf5d09e05647939421aeb3ac2f108bba
3413 F20101123_AABSVU pooput_c_Page_129thm.jpg
30f8ada81e82a2f7733fc19a1904ca9a
9f162d4932f4daf24c659d160a1b5f601fc49e16
5762 F20101123_AABRTH pooput_c_Page_066thm.jpg
57a884c32862e33c7a4d81a25410ad02
c6c421d9f24e30c9298c177f9439a9d635839300
1657 F20101123_AABRSS pooput_c_Page_075.txt
ca634b774e879e62d161456179e357dc
d0ba495e96654703980ee01bfddc880f9da2fa19
5332 F20101123_AABSVV pooput_c_Page_088thm.jpg
a2b9f14568b2fdde3ba702ca5a788490
893be73fab199f8ca0cf9d4bee892bc6ac7cc6c0
F20101123_AABRST pooput_c_Page_065.tif
53288a2c5d865fe321810616ef5e4d49
41947ddfebc45e0849dd19971b021869f5f6dfce
22469 F20101123_AABSWK pooput_c_Page_035.QC.jpg
152ca7ce54c3e5f2a0e95db758d9b40a
ff066656cf548c81d5084f7c354e38179d385330
5355 F20101123_AABSVW pooput_c_Page_034thm.jpg
af677a30759047c488d4afbb222fad90
7bbb5820b8c0106cad2f138c43982ec5324a20b9
34340 F20101123_AABRTI pooput_c_Page_016.pro
26bfac5091261ecdf620e4614d94184d
ed7ce88f5c6d8a3b3ef2d2af6282bc5f2d262284
46762 F20101123_AABRSU pooput_c_Page_082.jpg
df89a7e3cacce1bc69f85b4f81fcc801
0ff3647988e97dada5498ae4aadea7ee2755e84f
5349 F20101123_AABSXA pooput_c_Page_054thm.jpg
b08978faa0f848e3cee89f3c5e349cad
7e48b7da887141f6aeefb29500efcc663c34e863
5222 F20101123_AABSWL pooput_c_Page_071thm.jpg
9c1c4b752af51fa86bcc2c14836c6ae8
c11d50c9b0236b000aad43e5b25b82e65e3be0cb
5579 F20101123_AABSVX pooput_c_Page_003thm.jpg
8d3102f95a6e6b88ec4922edb2e09440
cf3bacef594c3ed08de10b3defb2e3aead9996a7
4766 F20101123_AABRTJ pooput_c_Page_009thm.jpg
f5b253ed92cf03679ea772b837ec2a43
ab5152082b72105a10a423f84de75689b46101eb
16561 F20101123_AABRSV pooput_c_Page_107.pro
187123079a25ae3475b8217b22178780
5c6a2abd86ba96a02d4be3f7eb08c070831b28d3
8183 F20101123_AABSXB pooput_c_Page_104.QC.jpg
98f19a4421152e01df0ceda03c266bf5
6d4bf33fac8b53f978243e08c34a3fd3becaf748
17305 F20101123_AABSWM pooput_c_Page_064.QC.jpg
a5a6b4fd338a95d8b6f29cb2379c5917
f297c0451681c2e441d9766a3f86fa52810f2ca9
5890 F20101123_AABSVY pooput_c_Page_097thm.jpg
730b1d47f29a820f59963f4af1529da0
7a2c6c3a90bf6931bcbd7e39ece57347c40252c3
4682 F20101123_AABRSW pooput_c_Page_072thm.jpg
8802e7addd875ccac53f579f16aa4d96
1769299c3aa7931e0c0afb93b63aafbd9823e509
15732 F20101123_AABRTK pooput_c_Page_125.pro
5442b9d606861275cf3ea71fc9d07763
a21a7223979a1266f83a5546396a4e82c63fe9e3
13645 F20101123_AABSXC pooput_c_Page_116.QC.jpg
c5433d8bd165445e524be5acae797753
fe602f14439e17a4801c2e7b28bd81ee4a0ba2a3
9441 F20101123_AABSWN pooput_c_Page_028.QC.jpg
26df03282ef75a47c6dd413403149e99
310201d67828269cca500614ac8b8bc758492dac
5211 F20101123_AABSVZ pooput_c_Page_030thm.jpg
b9be5a6d087f0864213dc9c12161fb5a
31adde6199fb7780aaf65adc1057bad422686b02
23928 F20101123_AABRSX pooput_c_Page_135.QC.jpg
04a0b2758eaf233f6fb09e5d0b27f45b
c66153425aa1742056376359d7c2cea2bc2eba6c
1642 F20101123_AABRUA pooput_c_Page_083.txt
5b9d4c54ae0796d4286a5b6b55a1caa8
5c4db91569c1612f04ebb91fa27a6ce110d3ef98
4905 F20101123_AABRTL pooput_c_Page_044thm.jpg
73a0315f05ef355f7b93edc81c243273
ab2907e0cbcd3c1c0376137d84f4eaa37c9a4cfd
18117 F20101123_AABSXD pooput_c_Page_086.QC.jpg
b220523345ac8d6604ec437bb583672c
e114f1b8fc024232513a1e2bf446fc7009c6b762
8801 F20101123_AABSWO pooput_c_Page_115.QC.jpg
d58048167cd4badefdfeb1eb8998deb7
2d8afce8fe7254de644b0020d9fb60b297bbf976
274438 F20101123_AABRSY pooput_c_Page_127.jp2
b8475efcf2245d4d15ab0ad9889d0628
e28d4ecde1ebaf6a9a04985be0b16cee963257f0
F20101123_AABRUB pooput_c_Page_029.tif
5b3c7564f47c91d81d34df6e77472b8e
0d3968e24c2744cb8ccb8013643bd01481d8a265
31543 F20101123_AABRTM pooput_c_Page_063.jp2
8f9977c99a8990deaef87e9346728221
6ca3229c3ff674aa318b8f2bab8f0f9a45052569
15914 F20101123_AABSXE pooput_c_Page_082.QC.jpg
56223391c2019b15a68df36b8e4238d5
cdb7f87c81edfd8cec7297384c02c5cade73674a
5662 F20101123_AABSWP pooput_c_Page_040thm.jpg
dc1e9f9663378f790d0fe7b50cf7fb01
eaccd3bf725e95b37bc2f6e68e34d8b10caa13f4
5683 F20101123_AABRSZ pooput_c_Page_085thm.jpg
9bec89fc9a8b23bddc0f979a57d53bd4
9933ccf4d8b03a2af738cd0cb2cd0a372a6871a7
13838 F20101123_AABRUC pooput_c_Page_121.pro
63d8bdefa9ba6e761ef3857d2fa817e2
1c6b69ab0508a2dd2424ffdba08e1bcca4165a23
4784 F20101123_AABRTN pooput_c_Page_087thm.jpg
49510cc728d4f17a63b2c2d4e3fd3fea
4bf2d5fc05463fe6a9ed9397dd5c93d5d45e4d37
3681 F20101123_AABSXF pooput_c_Page_089thm.jpg
84bd6e876ec62493cf091ce215c1a60f
db7f2d2836a3013b53336853527dc720c5b2047a
5603 F20101123_AABSWQ pooput_c_Page_050thm.jpg
c76262107a2d55ccb36a8e6e3ff840d0
02655dce9e30c4d4a03e6117f34c3f5c0a924733
13433 F20101123_AABRUD pooput_c_Page_068.jp2
968e8b66a92fca8ae867ace038838731
df4ad734bb28f5db72d942613474e7b10849a37d
9976 F20101123_AABRTO pooput_c_Page_060.QC.jpg
21e9d497d92ea25df8e4b2cb56c9c21e
518bdf4c0bebf521592f19317d15ff9d33dc7ceb
18195 F20101123_AABSXG pooput_c_Page_059.QC.jpg
7ae1e4809e7832fa44636fb450312261
7eecdeeffb511f4eed15f95061f628338d0ab9f3
5746 F20101123_AABSWR pooput_c_Page_019thm.jpg
b39d7716dd3d53d9c60bcc85874c32bd
067cb552dc3083a73302b500bccec10703ca808c
15248 F20101123_AABRUE pooput_c_Page_113.pro
b0584e0a3ead766b9842f0b23e557ed4
726a2542e66095fafc58ae0f13ae484a653c695f
61809 F20101123_AABRTP pooput_c_Page_038.jpg
d15d56fea3d546e0d6faac640762f14f
980238f4de90ff016827283b1c9b8afd8b1d1bbb
6060 F20101123_AABSXH pooput_c_Page_026thm.jpg
0236c2097865626c56eaafee6f9f1503
7636e244e1e46ced52d4a67ff40d5ad55253ef7d
19023 F20101123_AABSWS pooput_c_Page_133.QC.jpg
dfbe4f4adec3b7425c6d74bc2245a2a0
f006b75e618ce515bce6655fd9ed159af43d6061
3775 F20101123_AABRUF pooput_c_Page_107thm.jpg
87257a9aca40157abe28be51f0e548ca
69507a6a2e1af973b43720ffd1c7c39689400509
3246 F20101123_AABRTQ pooput_c_Page_102thm.jpg
9f1ec1bd98daa70cca382009eff3548d
43876cc4b215eaeb74bd9419aedbd0703d50224d
5772 F20101123_AABSXI pooput_c_Page_021thm.jpg
153f3d134f83b5adaf92d9ec33fd4584
5ea8a9a85ea540139effdc3c0b9d719e7eb63421
12024 F20101123_AABSWT pooput_c_Page_095.QC.jpg
6846762777ea05ed2a436cc97acce766
cbc0b80b0eedba6f5d7e8788eda91ae5017d801d
45730 F20101123_AABSAA pooput_c_Page_020.jpg
ae5bd3dc2cea7685432fc622d741272e
ed78f18345c539b53df8fed7e3b136c9c68a70ec
14296 F20101123_AABRUG pooput_c_Page_079.pro
89fd5ebc44a8e7a4913a89208eafad77
0f9f5e7ba1d9eae2dd88d7595dd7b5bfd0b68ad0
5219 F20101123_AABRTR pooput_c_Page_048thm.jpg
19b74bf06f3167ddce65c65ac0f8b0c8
07c0632da2d695c9f1c2376789c3ca5b3951bb2b
5391 F20101123_AABSXJ pooput_c_Page_008thm.jpg
da37c6537ee0ff9b0b0d67d96dc6dec3
6929d84ca4ca2425fe795d745d4fdf2fd4c55dcc
21850 F20101123_AABSWU pooput_c_Page_026.QC.jpg
e676ef13ffafd6ae09e2aa1043b97211
6f597f9321187ec321592b43058cd5dd8aece4f1
62530 F20101123_AABSAB pooput_c_Page_022.jpg
51ee9b33886258196a77ea001d635db7
4362f7cc60ef2d0b398d4a217d1bb4f08cac5a93
71006 F20101123_AABRUH pooput_c_Page_025.jp2
214e2c104dea9fdd3e03b15c9e99db01
c11ee06f54d51965c82adb357a472e3664c2b760
34759 F20101123_AABRTS pooput_c_Page_089.jpg
1c36717691c1fbcc6f6c709dab9d5d8f
8da89395d131bb4f6d323a639a0ba5a548cdecd7
2386 F20101123_AABSXK pooput_c_Page_090thm.jpg
7d466468fb2d41bc07bf0db307052d49
60dd12ff88d72194473b773452d2eb047d50b9de
8976 F20101123_AABSWV pooput_c_Page_123.QC.jpg
174319daf6d5f77ec76ed387c3e1a53f
7c200615b477633e082126f446727daaa68122df
51161 F20101123_AABSAC pooput_c_Page_024.jpg
c74b46f2c1b77657f0f625c29245bae4
6005492e54727b6f6055af56931d4ef038a774c9
5704 F20101123_AABRUI pooput_c_Page_043thm.jpg
fb6bb5ff52a85c66f41c5e2f6ab2f7e8
537bd5b5a77a43e5d255691e1cc96ccb78e97311
3845 F20101123_AABRTT pooput_c_Page_018thm.jpg
d430cc9c844af2b24f08f63f1ed84e55
cb62e73477f7585393154e5a472059429d320ee4
22801 F20101123_AABSWW pooput_c_Page_065.QC.jpg
3e25cbacbc4c494f94c6096aec631b57
8bc9abff2809ccacc2ead307371c433476b641b6
59551 F20101123_AABSAD pooput_c_Page_025.jpg
97b9b3b09b473c40320e04728fe1a637
e7506dd0adaf9894d844d8436171d434a5f3d3e2
232 F20101123_AABRTU pooput_c_Page_015.txt
45920043906f55471e0a74c05e6c618a
4bc63e8dd58e3ab1a4ce04a7676aeb3cf6e89c60
6394 F20101123_AABSYA pooput_c_Page_037thm.jpg
db8601ff686eaf3c8108d8dc38c6f08b
1770749161e320a467c946cb321aee1ee0212a16
8457 F20101123_AABSXL pooput_c_Page_127.QC.jpg
1b97ba9b21c1d5f1c6e7589ffdd54b48
c939e7a12c1ff9e767d83ef232505e7b357568d2
12547 F20101123_AABSWX pooput_c_Page_124.QC.jpg
762cd73176b87ff7c7370f9a36059010
fe8f34b34998928bd17d1e39966037079b7d9e70
66759 F20101123_AABSAE pooput_c_Page_026.jpg
2b640b643bfacd5ee2d664b4441935da
8d38ea1c4e7caed0ab06880f5d985e368134a5da
4744 F20101123_AABRUJ pooput_c_Page_099thm.jpg
8db6d09d8f575d5830b61e426fb4cc29
c95d88e79d5408d74525686de66e4edf18a2a6f0
21447 F20101123_AABRTV pooput_c_Page_067.QC.jpg
88196eef0edbfd2439f985f303b7ba2f
eec182d54c2daedf72d54108e68528919f63a48b
3002 F20101123_AABSYB pooput_c_Page_028thm.jpg
1601f2c2d71ef624248c6978c7645cc7
43c36837765d80bf7f386b7d5c1c97e2c3c021d9
4660 F20101123_AABSXM pooput_c_Page_083thm.jpg
5506a9777407d0cc7fda62e125e4b0a4
70eb6bd7238661678fd87dfb9ff0ee7b35c24eb1
17928 F20101123_AABSWY pooput_c_Page_021.QC.jpg
149e58ee04fc31d5fcbfad465f58216a
0c2a05d6d5cf3eaf253ce46e02318c57318b085b
60133 F20101123_AABSAF pooput_c_Page_027.jpg
071167dbce8f35b43dd3defc3452130b
232781b48041e00cecd51535f6ed47092d51df17
19687 F20101123_AABRUK pooput_c_Page_058.QC.jpg
6094a0148daaefc9b829e9dbe4181c9e
0ebb10c5dff2edd32801bf6af3e91632cde92166
36622 F20101123_AABRTW pooput_c_Page_122.jpg
1f50a6b36e60fd9baf8972cae8b23ddf
ff1524a56e44785cb6e35ead2c5aec5fb1ce7136
21403 F20101123_AABSYC pooput_c_Page_013.QC.jpg
c1e141a2b9cd9c31ab58a48d568b9773
702fc152d13184a2cd85e92ae69cf79d8c4a0349
3350 F20101123_AABSXN pooput_c_Page_121thm.jpg
84273c997b3000f1e96906c5cd1d6003
c836f8da8fb1818341d7e7fc7bb06b61162ff746
6557 F20101123_AABSWZ pooput_c_Page_005thm.jpg
4f361421d3a131bb7507d0c06216ac7a
4598cf3190614817aa2ab8e211931a2e4aa3d861
29941 F20101123_AABSAG pooput_c_Page_028.jpg
e86a6cb30b4758450563eff36ef68756
c3083932ac693bbf5ec52e81a1c775c8082884f2
3190 F20101123_AABRVA pooput_c_Page_017thm.jpg
0c8a9d56f02cacda8d91c3ed21d5d7f3
db4df809b2b30485123bd692bfc8765106026687
5333 F20101123_AABRUL pooput_c_Page_109thm.jpg
4610b1b5900278a4647a8af0731982fd
152feff3af28f621d4da0def0f98df6cb3583695
F20101123_AABRTX pooput_c_Page_049.tif
8b3c8610950422791ce803a632981f82
0dd0d357c8e02b73210ad145adeb6f2d4363c7fd
23615 F20101123_AABSYD pooput_c_Page_136.QC.jpg
67ee6871aed9d897958ebf5e2da8d890
db515a48e4631e590a2b7c43a304688693c4b69f
21371 F20101123_AABSXO pooput_c_Page_031.QC.jpg
2c52d1f6b94f6c21a00bbd7ea31a721a
2f5def4ab36c2793c54c5cc16986d502af72cc61
42513 F20101123_AABSAH pooput_c_Page_029.jpg
be83dab45aa4c570f442a66847df3673
eb1b5a60c8f2a00fba7e635afd1f72cefe977aa0
F20101123_AABRVB pooput_c_Page_025.tif
aecd315a6c6e40bb36b6e7135d1b4142
58617f82da0dfac87755bb181367102ba6d636c6
17520 F20101123_AABRUM pooput_c_Page_089.pro
c451041940a361e6e7787e524844ac58
dfbb4aff007eadd912d75f0148575bb93a430b45
69097 F20101123_AABRTY pooput_c_Page_065.jpg
70a7643b437a1eec9876ff0ee94190d6
0b2d800c416c4fcccceedc5c1cfde3774a1ad1bc
8656 F20101123_AABSYE pooput_c_Page_131.QC.jpg
d09ea1285a609c6769f839985d0c28d6
426e7406dded69d4d0419b30f1146d3439a89a4d
3857 F20101123_AABSXP pooput_c_Page_122thm.jpg
d4d2533e0362025bc848975d6b3ce543
5f0ccebe88a3a6d08107791c8877c58378db89cb
37855 F20101123_AABRVC pooput_c_Page_058.pro
e1bd40e39c11e247ea84ca13e4cfe14a
675eab435f3a59c236e4769593d4985b88771627
25478 F20101123_AABRUN pooput_c_Page_129.jpg
de4ab16fc432db43bdb4de9dff6af0f1
9f404ac652e92441105f1aaeb6b867f8cc7d55a0
6676 F20101123_AABRTZ pooput_c_Page_090.QC.jpg
1e93e71f46fb43c01795ce6850568470
a541cba66e6841670552a86ab3d84e7524801db6
49752 F20101123_AABSAI pooput_c_Page_030.jpg
213f56798a60ce38dde46e69961020d0
862ae9c48898ef2acf1fe4125b01402536f0eb9d
207864 F20101123_AABSYF UFE0011625_00001.xml FULL
1cd9f90e5f24ce78f022a3557ad3185d
b36dc6dbd00afab5617abeff3fd50ae814c0e386
6367 F20101123_AABSXQ pooput_c_Page_065thm.jpg
fd9e4b3b30d81bb93abc7899dfe73d67
c9d8a80b59f10d1a0e9395d055b199f4d7b475d3
12009 F20101123_AABRVD pooput_c_Page_018.QC.jpg
a5d87cde15f6183396c5f894128acdc7
fba7c16bed9ee1d9de3b85994f9aef21ab0cdf7d
61747 F20101123_AABRUO pooput_c_Page_020.jp2
0d7940425161b4e967ca842291119b50
60b1bbdc77c1b427e28778a8f600dd7973fbde17
63049 F20101123_AABSAJ pooput_c_Page_031.jpg
2533b517787400c5a9d20758e7080032
ceb5ec598b8fd508f8f77fc5cb67db3605d26774
17902 F20101123_AABSYG pooput_c_Page_004.QC.jpg
f215a448adee02389d429ee79c9df281
734c459d3c38363b258fe8e8a7543989a8fae291
6034 F20101123_AABSXR pooput_c_Page_031thm.jpg
de3b8daa1c1bd19d364b3c69931f3947
e74d8618db9fe37256e528ff506264cf5e7b4ff6
58008 F20101123_AABRVE pooput_c_Page_009.jpg
b5b8b17baed7b0c23339f76236f55424
4d7b9658774de301d6f65866a44e9affb17cf564
F20101123_AABRUP pooput_c_Page_060.tif
7717011ee8731578d9864b90b6def3bd
d1ecddd17ee3bb79cafd03960b9cb2a685712499
55695 F20101123_AABSAK pooput_c_Page_032.jpg
e6be71ff24f26d5bd7eece81fbf8234a
ee53ee4e37c16c5f7b0d3358ba24aac91f1bf705
6403 F20101123_AABSYH pooput_c_Page_006thm.jpg
70910bc8a1c4826e27fad64daa44bab0
883aaa472ad6833dbe7bfa47296850a36a4c3032
13531 F20101123_AABSXS pooput_c_Page_098.QC.jpg
19042f455250a8b5cd59abefe964e009
353d0aebaa42b5dbe1e690e912fbaf9b0d5bb5a3
43825 F20101123_AABRVF pooput_c_Page_023.jpg
95c7dab53ba7bee18f152f855e15802e
93a74f33565ace2c6e640055872861755a0d0b86
7559 F20101123_AABRUQ pooput_c_Page_007.QC.jpg
8115f0dddfdd43f097bf1afd69a7d336
d696790d0e66ad0b3dcf9cc052293863f464be43
59905 F20101123_AABSAL pooput_c_Page_033.jpg
2919fbd9ba7183ff61c20c118f4641d6
5201e231fc2e195c39d402a1533a2badd02ac143
23637 F20101123_AABSYI pooput_c_Page_011.QC.jpg
680455ed57e7e24131df2e6ca80cbf57
72d39e5845baab58129f851dc2ad952c71e6cc9c
16958 F20101123_AABSXT pooput_c_Page_009.QC.jpg
f83046b6b7a56a9b0b66da5773d4eaf1
8e1c0bb5933e020092d96bca1b2e7b3904513766
34039 F20101123_AABRVG pooput_c_Page_112.pro
ed7fd16985be5cbbb836cc6abd523683
560f041ccd5bb501f368c7da7222f303a7e38ead
18765 F20101123_AABRUR pooput_c_Page_043.QC.jpg
46508b743136c9a80996d56815834e5b
0188d7734a063cecda46febc24c9989a00f0c014
69270 F20101123_AABSBA pooput_c_Page_053.jpg
964ade46e2816016ec6ef1ac26f9a023
6d96367cdce66f8b847262bf31bae3ca24f18dd4
56368 F20101123_AABSAM pooput_c_Page_034.jpg
74167e73de1bc7f18b801d343bb9defc
543a350ebf784046c19927421732266277f47c2d
3526 F20101123_AABSYJ pooput_c_Page_012thm.jpg
83ea9f95dab308b96191ba214d7e0e9c
b010f7695f758092d8d88c154f1265ed4fa392a0
6317 F20101123_AABSXU pooput_c_Page_014thm.jpg
b9c791c515d81ba74ae5dda793ba20d3
1daf6dd2679ec375cadb25e8e2dce079b1c9b516
2744 F20101123_AABRVH pooput_c_Page_079thm.jpg
1e391a967909477a3a1a0d553ac42727
634853c820350f252464baa0ee29e65518d6eff5
5817 F20101123_AABRUS pooput_c_Page_015.pro
52b9af15bef020c45e0b94529d880df6
304a2243504ad821ca4ec11eae4b8a6b3b30c0fc
58002 F20101123_AABSBB pooput_c_Page_054.jpg
b5a4377a3d032f5f07b1034b8965432b
2b90e6e7a46bada249b4d66fca27f704877b027a
70429 F20101123_AABSAN pooput_c_Page_035.jpg
a6558f5ba2ea156b0e068cf22ecb49ee
46c795cc120ff04fa23b29466d464c4d52ab0d21
4237 F20101123_AABSYK pooput_c_Page_015.QC.jpg
a0a7ba0e5d46e32aa86d1d3f9260fc78
d4e86057b27356aa7a18c7c9632fdab9b165f5d1
4554 F20101123_AABSXV pooput_c_Page_112thm.jpg
96b778974e50fa5d40293a828077d2f2
74a4575931fbf09daf716537c5178e98b072b582
36158 F20101123_AABRVI pooput_c_Page_122.jp2
62c1b31294e2ebaa33c0c379eccff2bb
61d7cc60df962d60d8325b7266a02c548e71d032
13108 F20101123_AABRUT pooput_c_Page_063.pro
d49253ca1b6b8a383b4acd7a6a6a167f
796a09b85bc4e081799b0fe18e246f58b7f841c0
57312 F20101123_AABSBC pooput_c_Page_056.jpg
7f8bdbbcf3b09109e2465eca2a4e42da
236bf37785f4a1efeba337aeae84b4f364e1e9cd
58644 F20101123_AABSAO pooput_c_Page_036.jpg
3d85e56bbf16107394d992f099afa06f
f32376cbce24caa2cb4ca68677187e3ba193ddb8
16953 F20101123_AABSYL pooput_c_Page_016.QC.jpg
ce9a2eec5c6474174455eb7bd71e4e7d
a6093a45ee8442581bc9b8cf69237033e8921869
14781 F20101123_AABSXW pooput_c_Page_093.QC.jpg
39da41de48a0e44f7099dd61a4201eb2
0a16151d503a887f6ba1fe574278f9663782e5ae
1742 F20101123_AABRVJ pooput_c_Page_031.txt
bd6c5a4c4e1aa37a355317871d44ff0b
dc4fd24f894c1cc01b91b17e791662b47018a71e
18331 F20101123_AABRUU pooput_c_Page_126.pro
7576fa03f503ca3c64ea58a1385e6119
154e86315a3384abfa85fe91f3d739104c0cb08a
68464 F20101123_AABSBD pooput_c_Page_057.jpg
e966af9138c2d10aa67c8ef6c92d7ab3
55689cd427719d79a626f98dbcc606a7e84637dd
71567 F20101123_AABSAP pooput_c_Page_037.jpg
82ee63f51c0cc4d1d518a5dad66560bf
126b1d2de1fe03de48db7c952e1dea772df58c14
14249 F20101123_AABSZA pooput_c_Page_061.QC.jpg
811cf4a188bfef74b82c36e9747a6451
298a1204afb0dc20e5115408d39c26b55c2c4191
7098 F20101123_AABSXX pooput_c_Page_001.QC.jpg
bc65c9d6a3984113c9bec07cce0c8fba
5e7adb897c8a943f36d0e1c3a12fded90563f50e
1227 F20101123_AABRUV pooput_c_Page_103.txt
6afdc689fdc88fc655345c3d6f4bf362
597e148eca5d472918efa118561d53e25c34b28a
58744 F20101123_AABSBE pooput_c_Page_058.jpg
f41b93c8a6bb68486cd4319900153b74
334e03ef055eeec252ae90305d067d6f4f56a0cf
60322 F20101123_AABSAQ pooput_c_Page_039.jpg
2bded9a9dd47b5a875425917a107b3fc
85d3d14a5da1078e399ce6468d890195c6cf3876
5687 F20101123_AABSZB pooput_c_Page_062thm.jpg
f32b3c4f581523f0a30fffd579886a2b
13e4e534f6a9667e56b73831cc489f7f173d20f2
19735 F20101123_AABSYM pooput_c_Page_019.QC.jpg
e2e677ba9bf79781971cb13aa8e56446
922c227b5c9b8e49a3cbed8accb8029aecca7911
6185 F20101123_AABSXY pooput_c_Page_096.QC.jpg
9d4bd5f5db90f9254f8d83616775ccb2
e0678d60472d1b84264da021f08216ec29e8840c
1139 F20101123_AABRVK pooput_c_Page_045.txt
4a74e316c82b05588a5850917618e58c
f8a86790d771e73a59a85da3ce6725dff2695fb4
3992 F20101123_AABRUW pooput_c_Page_101thm.jpg
793dc1749ecd24faf16980f244a72731
f613f5af72ac745cf7205a5ee458a296085ae21d
53888 F20101123_AABSBF pooput_c_Page_059.jpg
6cd843f7761876edb7511cb63b569dd9
b8ef8f1ee45e9451bdfe42e9b5fb82c3cf4f2678
19896 F20101123_AABSAR pooput_c_Page_041.jpg
a7c7f5f0d8ecc8b728b9196605da08ad
98784d5f46817b1b5370d4aeac16a6a13638c493
4112 F20101123_AABSZC pooput_c_Page_063thm.jpg
3bcf69eebf1755f2e17fafd1581b7c3e
30aaf910d9d968b7de47c103ea37d638d1f1f5e6
19761 F20101123_AABSYN pooput_c_Page_025.QC.jpg
4c56e53e2fcab3cbad2bf80bc72a15a0
22a874e983142ae6e991d774850dbb5daf6e1e7e
10786 F20101123_AABSXZ pooput_c_Page_046.QC.jpg
bc8004ef0cf4428e351b9fd0f1529882
88989159d1205b889dcafa870833231f89ea7321
19260 F20101123_AABRVL pooput_c_Page_040.QC.jpg
790e89fa72f5b8a251b6ee92ccbc4d7a
446df63d5c17db0f420f5fdbcaeaa3b1c131b8a6
F20101123_AABRUX pooput_c_Page_121.tif
756d2884034b08d399d2fe8bc87c6e7e
987d06b5a00788ea8e73128e1e1ebc3b18cfb16b
29713 F20101123_AABSBG pooput_c_Page_060.jpg
50d487a510119e1eab55dcc086e43ee0
413dda249adc570c2c01b5d873ac89a014100370
41357 F20101123_AABRWA pooput_c_Page_012.jpg
e6a9e7d6c5ae227383a3bd970762cb02
49b32ef32d30594a2e849ff17b507a1ca09c8f22
51380 F20101123_AABSAS pooput_c_Page_042.jpg
234d5033ae8749ea8542ee94011890bb
4b05960fbdd22aacaded420d81581c898fe413b1
5788 F20101123_AABSZD pooput_c_Page_069thm.jpg
b77bd97908a32f55e135bdee04eda17f
a476bafd10b6e324995340d864dad5bd93ddcd1a
20661 F20101123_AABSYO pooput_c_Page_027.QC.jpg
17cff3844ff8dc37a660301b821fe09e
31a61a1c101b51baff212532e6f16e1f384d1c90
39951 F20101123_AABRVM pooput_c_Page_027.pro
161ce355323fe8f30cf42e5e7405f251
3ed98754577db0dc282bbded511e13420373993e
14414 F20101123_AABRUY pooput_c_Page_108.pro
b0d21354b13941be716c8ac7b0df5e65
9be4f88e450567c0d7d56cc6ac052e350c2799c6
42796 F20101123_AABSBH pooput_c_Page_061.jpg
f2427e1f18485ca194bcc72947d1f0ec
e082d4e3d422321f2bb112df4cdc698f3c271a0b
F20101123_AABRWB pooput_c_Page_122.txt
e6624921ed6786f2229ea53663358a19
15316b42fdf3f6686109ab10291d7ab6d33e30bb
55734 F20101123_AABSAT pooput_c_Page_043.jpg
c345d5d75ad3e523fafe5191e8a55d54
af1947833f3065d9f0154f9401951d376588f017
4254 F20101123_AABSZE pooput_c_Page_070thm.jpg
4622fac80794bf655df27b5044b041b1
b89dfad120b8406a26b6977152abd0a15127cb0c
5384 F20101123_AABSYP pooput_c_Page_032thm.jpg
01e061152624a0d58c6b668e2dd4beb2
d0f8eabec9f93c10b68d5f539444e6d99d793f09
30290 F20101123_AABRVN pooput_c_Page_082.pro
56e8fa1bdbaefd09ce46ee5ee5a8c1ae
cbac14702e21a6512d657a9046d78468e3270d60
1057 F20101123_AABRUZ pooput_c_Page_114.txt
911c0be0af55382026206fb5b6918f98
190818e7f991495bc1e81a5dbb677f9459d84397
60642 F20101123_AABSBI pooput_c_Page_062.jpg
039944806eee9b1b8776ba1a670742aa
ccff887aadfd27fc00de09bb7cbf9d86c7559469
1876 F20101123_AABRWC pooput_c_Page_032.txt
9b6770cbff99d171693838c5d8b5355a
eca52430b10fb8256abd47947be1f67c878578f5
16162 F20101123_AABSZF pooput_c_Page_074.QC.jpg
c01957371b657d807b7901d397e5b060
6eaeb58d5592246cbb9d399605035b3e3a5554a3
5989 F20101123_AABSYQ pooput_c_Page_033thm.jpg
5a9ddd931ec86b54e212aa4e845f5434
462df723e640864088ee8d97cc8079531eafb8fe
1651 F20101123_AABRVO pooput_c_Page_099.txt
b71d593fd38b498147b8674d8dbdc3d1
3085d48b5848803cfa9b4d2f0dd109d233320148
32200 F20101123_AABSBJ pooput_c_Page_063.jpg
28797a4c30b807c46a73f00f31110ca3
7e33a01ae525504de216f01f8f0ae35c893246c7
37896 F20101123_AABRWD pooput_c_Page_054.pro
5c993dfcba921b518516d5a065e3a77c
65253660954c717214a9f00b26108744be4cc7ba
29350 F20101123_AABSAU pooput_c_Page_046.jpg
d97cae77129737853f7bc563bc5fc7fb
a01df2c630b745754ec7eb590d0167a8f626d339
21714 F20101123_AABSZG pooput_c_Page_078.QC.jpg
fdfc5cfe32b2200f6af24322b4908af4
a522d9f4379452c57e3792be60fa30c7f06ab901
6048 F20101123_AABSYR pooput_c_Page_038thm.jpg
cbc3a1b2abf9380c1e3f413a19e386c5
e0f6c4bf1211801fddf037872961224896573ced
12227 F20101123_AABRVP pooput_c_Page_120.QC.jpg
30bd3c22a426af3e6510d586d8653b84
8bbe861bfacfce27dc11afc66ec407760079fde7
50224 F20101123_AABSBK pooput_c_Page_064.jpg
282c8898ce9678891ee804afe461ed46
ea9186437a9c46911a2a672fe1be83bfa6e2bf74
854 F20101123_AABRWE pooput_c_Page_121.txt
b15c9d6a77f7d470e014b0336995232b
85f66b108a72adc411d65d8a1a9f42a34eacd5db
32740 F20101123_AABSAV pooput_c_Page_047.jpg
32d82b3b61caa0baa9ac59e4fc88e308
f488d44d18700277cd4820fab8556a1b05a91f1c
F20101123_AABSZH pooput_c_Page_084thm.jpg
95ea8ab8ddc24419242ec35171bb357c
f4ba2dcfa10b90131039dc33b9199161ade25e50
13664 F20101123_AABSYS pooput_c_Page_045.QC.jpg
8644875764b8626461e4803c7a90d6c8
19ef184fa58ff3b8f803ea53719621da4caa20c9
1802 F20101123_AABRVQ pooput_c_Page_068thm.jpg
254ef0f0a5e845a29cd83b42b11c2220
e467153ff9b1b216aa648f004a22b0426fab17ad
60250 F20101123_AABSBL pooput_c_Page_066.jpg
5c9f40fef952ef24e027fe629de424aa
2581e8a1abf9fafc7ae91822416ae264f5f7e060
28480 F20101123_AABRWF pooput_c_Page_046.jp2
b606ff6d899b9c8df1cc42defab4eebe
4af564540ba74f2dd5e03d3c8a9199c2e17a5817
51329 F20101123_AABSAW pooput_c_Page_048.jpg
c62feac503dbad9b532c897a2ae73911
9c17813f236d3c7cc49f55d04ff35ea971c518c3
19150 F20101123_AABSZI pooput_c_Page_085.QC.jpg
c8e7a72eb6631724d543f1858106cc67
6184a6a7507c384ac6f8b527e2ae67d3574fd3cb
F20101123_AABSYT pooput_c_Page_045thm.jpg
1094282cab47966c112a00b67f7a67bf
3aba31b78deb0b337b580287254ad7f7df49d261
40918 F20101123_AABRVR pooput_c_Page_095.jp2
972887deaf9ff9b0602979b150e81183
33bf8bb2e661c13b4040ac340b09f00d4c14b54f
55445 F20101123_AABSCA pooput_c_Page_085.jpg
60063f23f610be0aecfd09ab66ef15db
d1119fd7d7d79bca2aff1884c68d9be6c2d762eb
63930 F20101123_AABSBM pooput_c_Page_067.jpg
b10140a05768cba4f502cef0c9b55ae1
8e75a7fd8532c9c61dccbdb1f77c1f02af01cbcb
F20101123_AABRWG pooput_c_Page_012.QC.jpg
3e28007641f09a9f2c682955759c4cf0
475b796ad8a13c25c35110fcfbf141735dbdbcf3
41988 F20101123_AABSAX pooput_c_Page_049.jpg
d35cd0566d4acfb804c6855d078550a8
d0b5c1372f08c253aa8bec1fd8189cceb36752d4
16068 F20101123_AABSZJ pooput_c_Page_087.QC.jpg
9a02bd77634329aa4f608a6a70b0a90f
459c2f350b8a2f7aa6f193b0fec563a30bc2f764
3760 F20101123_AABSYU pooput_c_Page_046thm.jpg
b28d82d0d8ad301ddd1d1cf21e7aacca
91b3d6b4abdc3ce765926fb48489dcf330a0e9c0
F20101123_AABRVS pooput_c_Page_003.tif
c845af948d8aeebd6a02837a78ed0e9c
af457bd7a4b09636f4831e5f2692068257629fbf
52376 F20101123_AABSCB pooput_c_Page_086.jpg
5d057e4a55af5735a4f6b238d6dadb0a
7166752e5f2f20c2e55f5d1345d49fea87c43271
59175 F20101123_AABSBN pooput_c_Page_069.jpg
446d0f2fcc14c8fe9d89a83539b41b0c
3329f231ff9976b1ac2642710badfa4a0956bd57
F20101123_AABRWH pooput_c_Page_011.tif
83367793307409e8136acbfc20124bfb
be962cccef77269b71cfa87a4d9c29511ad7feda
69656 F20101123_AABSAY pooput_c_Page_051.jpg
2d258609994f28545f585edca0846681
b00c25b51f46d18e6eb688a31f779a3307d1f61c
11186 F20101123_AABSZK pooput_c_Page_089.QC.jpg
41a0dfcbea9a76561181d69f53d70038
389bdda4e7e1ad81763bd54928f2a4cec0936168
19598 F20101123_AABSYV pooput_c_Page_050.QC.jpg
a5f52119c0e31f20138c91c1a1b85150
8f0a13b330bdb28a89c4e8993a5e8c32f5a3b651
F20101123_AABRVT pooput_c_Page_085.tif
f49cc56fe6856666d762ac31f3759deb
325900d775424b0f2d685daff3945f18cf91e270
49944 F20101123_AABSCC pooput_c_Page_087.jpg
ced7d0b54ebae6011b085149b4a5d73e
3a32466110f4d4af719190dc3e20d5ce98173fb9
41953 F20101123_AABSBO pooput_c_Page_070.jpg
9891f0443484e1f1d52c32d770b10dba
020f0273df392ba1a10d4600832b2fa7d193ad80
26918 F20101123_AABRWI pooput_c_Page_138.jpg
e400331f91b1f7bda77c07104d37a776
ca763af0bc274ca932c431cdfbac2d8baa68d1f4
57491 F20101123_AABSAZ pooput_c_Page_052.jpg
2e955b0e10c190c12fd63b7b8c7199af
1ec83240e5e0ddc43fc8aaae83eb5fc2485f68ba
17484 F20101123_AABSZL pooput_c_Page_091.QC.jpg
cb9f721fa0c109458fd30d36ba99e9c4
2a65b9877c1611c03aaccc86e5fa4b814225cba7
5364 F20101123_AABSYW pooput_c_Page_052thm.jpg
92c3b686731bfa2b9c4db8e771fe3bc7
5128ebc7bfb21f3b4240125c4e2f22ddb0d15ae2
43676 F20101123_AABRVU pooput_c_Page_045.jp2
485be422473515191f8e02bad0228ea0
f3b43d2b0eb91dd8147e58cc8988004f52859fbe
54217 F20101123_AABSCD pooput_c_Page_088.jpg
5a83c3e03a6040822ba05acce747f2db
218de5c7311121ad1fb9f1ee80156d9031f3b3cc
48941 F20101123_AABSBP pooput_c_Page_071.jpg
c8d37b89163d1ae695897137714efac0
e3bf62740baeebb67dd2ad96e0a9d7e68d7bdfc3
41344 F20101123_AABRWJ pooput_c_Page_097.pro
86dc2e2060ee9aadf38a8af8e09a3af4
59831fcabc2642e728e93fe3388ad214ba17ec8a
5190 F20101123_AABSZM pooput_c_Page_091thm.jpg
3ba21a56ef3abd942aadef3873b39ac3
98dccdb541a778df25274f1108e342f29c74c461
22675 F20101123_AABSYX pooput_c_Page_057.QC.jpg
d2a7f7e134fdb7890a76e25f1e2b1149
0b9ea7fbac8204f5cfd1713935b40d5bcfea2dbf
4641 F20101123_AABRVV pooput_c_Page_049thm.jpg
fbc780c7b67a111152a989fd07940f2a
60216b87806a099739e0fb4fa3f219fac963f044
19616 F20101123_AABSCE pooput_c_Page_090.jpg
930334624b4184fc7aa3de7c6c5a578f
4a33d9a770baed934ab826a6708fe8ec03123626
41439 F20101123_AABSBQ pooput_c_Page_072.jpg
78da467019bcee5cf3e50e74d90a118a
6bcf3ca11fae4c3af0b626776b771c47362e2594
4798 F20101123_AABRWK pooput_c_Page_042thm.jpg
fead7b9a9690e5962cc9ae443f15ca45
ad55561d4ab2e774bddcc8e0f1b9395218d184c1
6472 F20101123_AABSYY pooput_c_Page_057thm.jpg
7522b4f0e5ec887d0e515a1bec90ed1c
54bd48e0818ce1118e0db14065d373d6a2a06d2f
25182 F20101123_AABRVW pooput_c_Page_083.pro
18adda94b684a67458e3cfbbfc67691a
20f2972b4d685671bce121f71db52d0bc14ac8cb
46844 F20101123_AABSCF pooput_c_Page_093.jpg
37e2aa65aba9aab458b5277e8ff727cd
ed94adc2bc92d6dffce750da76114e33c0c10df1
63345 F20101123_AABSBR pooput_c_Page_073.jpg
543d9fbeb4804df4d8a4a32297b6f973
4a5049c68bf4e0bf2aaddc89a1bd7f85a10bc7c5
4942 F20101123_AABSZN pooput_c_Page_092thm.jpg
532a17a14cac1e297e95a0eeb88e7351
ee9e069ae3f7c36ebd8233f7376230a0dc416a5b
3226 F20101123_AABSYZ pooput_c_Page_060thm.jpg
eab4d2d62bc5afe2c511fea7cae0165d
a448b45b48c0228b836158d52e6701e19cbe2121
18031 F20101123_AABRVX pooput_c_Page_109.QC.jpg
8a892e767d5f8d99cf61dfbb695d7263
f79c263ea9ec40148cfc0dc69db5dee5ad05eca6
53398 F20101123_AABSCG pooput_c_Page_094.jpg
f179300180a1561e00161187da78e696
39b334ad1043339c5d1fa7dc838b76c8a916e208
1805 F20101123_AABRXA pooput_c_Page_051.txt
145b2263c9d8d30ffe8c8922410beb1f
d9d9c580594c498c0c6ac63c28cd174d2e3a32d0
54848 F20101123_AABSBS pooput_c_Page_075.jpg
88c5e2ee43651e224b099de95123298a
8f499ef868f0030cfc43d47f0c2a4960eab7d807
36202 F20101123_AABRWL pooput_c_Page_124.jp2
4f56f738931f26d0317d0ac3456628c5
1f94d70a214b9fe243ceafbe87fea220280e7773
4582 F20101123_AABSZO pooput_c_Page_093thm.jpg
f3ddecdd5ac3234029e8fea89f039d62
5c97940128207cf4ce15cea96496fa46d3cdd0e5
F20101123_AABRVY pooput_c_Page_130.tif
5297c346045ba7ab26316d749c0fe22f
321b63d89afef2343b783260f96630749472715b
38073 F20101123_AABSCH pooput_c_Page_095.jpg
15c944056750fc7a3cc873e126053944
c4d2b89dabd71ed11f8d7db2171d5a29b673f009
1789 F20101123_AABRXB pooput_c_Page_022.txt
80b972aec5c7fa5b77681efb047e05b1
bb1725e118e95ff517c7a82ed8c7872c3c091b9d
45455 F20101123_AABSBT pooput_c_Page_076.jpg
7581e834a486da830c76d3154aa26cc6
3c1d49d61498d8ff542a58e9e6d26a75e8859563
1712 F20101123_AABRWM pooput_c_Page_097.txt
77042dbb5488fcee6f10dbf110525638
bf29c8603a40a1614ed7643d7066520e97aca6ee
2357 F20101123_AABSZP pooput_c_Page_096thm.jpg
a04803a53025b67696b128da4b611291
7410dc5f59a0a95becafd6d00ad2adf2e7ba4ecb
2131 F20101123_AABRVZ pooput_c_Page_134.txt
539ef252a1d082e0de0c8aeaece38861
1d46ecfbe3c53c28650eed639ddd4a74777e95ce
17877 F20101123_AABSCI pooput_c_Page_096.jpg
dcba16ea1c4e2c2d76b5e2b7862cd0ae
a52de599a29e44557408c297e7c46b7c44adedc6
1051970 F20101123_AABRXC pooput_c_Page_005.jp2
32bf633621e531a3c5f9058e69df5ea3
f83739554f1412da6763a3c35b2c62bde6986a6f
67178 F20101123_AABSBU pooput_c_Page_077.jpg
9ccb4d757d4c7ee8f0292c964903ddfb
2251a0735fada4d59d76efb7c254fe2358346dd5
290130 F20101123_AABRWN pooput_c_Page_123.jp2
1a6c5a7c70b5fabaf7b16906f046a63d
65ccb8032274b8ba9b8b28872a7d6946c213b51e
4019 F20101123_AABSZQ pooput_c_Page_098thm.jpg
b1ade6b8f5bd5200ce6fdc67ab847c27
01bf1db293409ba2e58484e5ed04738527143bc8
63600 F20101123_AABSCJ pooput_c_Page_097.jpg
56c2f5a940fb47694a9d505c8fddc0ae
b65d920e67e7fd15052f784dd7eaf174d5ae1072
5842 F20101123_AABRXD pooput_c_Page_058thm.jpg
3c0968e3d70b6db0420147e0ace9f544
e55ad847005cac019d7b5d3f9878ead02aea49c3
64882 F20101123_AABRWO pooput_c_Page_080.jpg
552636c51d9fff03f04692bbdf9319a3
ccbbec8717c5e0c59271d07225f002a274f9a84d
9611 F20101123_AABSZR pooput_c_Page_102.QC.jpg
34a0b686ed29653105271f4b6ed7d4e0
eb02be48de89fa397872248e570838aed08d92d0
40208 F20101123_AABSCK pooput_c_Page_098.jpg
c2b82f36cd1b41492705b05352c45650
6af30b5900152c72f969840c9ce7ba88c34cb8ba
F20101123_AABRXE pooput_c_Page_094.tif
71b7db8f79cc6d21cb9efec307b3ee08
0e0f0e0f19e12386f21e478866e6c1aa7a58b9e6
64985 F20101123_AABSBV pooput_c_Page_078.jpg
cccf93510ed4369874cbad6c2d1d2862
34d5c0e88c3024d781d97c6210257ccc35c8ab50
3407 F20101123_AABRWP pooput_c_Page_131thm.jpg
4d0317d21e5287e2e27df9a0591cd151
d3c50a344a28020fc616ff51a775dd535a8719c3
3999 F20101123_AABSZS pooput_c_Page_105thm.jpg
031b16f1ed6482b05d427a5814c0a184
380aa39585fb5d278ebb88f59be628c0bf5442f8
46604 F20101123_AABSCL pooput_c_Page_099.jpg
5240bb6f800f635b2e06e9c0d918783b
cb193cc08bd77ab9f6d04d5ae883f8ba1da11f56
88381 F20101123_AABRXF pooput_c_Page_038.jp2
30fd4add54cca17de914e7db3dfaa7be
ee6d8dcc815f62abc47b34a87d8a1c7adcb0a353
26303 F20101123_AABSBW pooput_c_Page_079.jpg
052f3557df1d57a3a9bfd2fa9830ea05
e72dd20922b96438b8301a8796c8decdf7ab757f
6671 F20101123_AABRWQ pooput_c_Page_135thm.jpg
ba971ec9566535e9423b65fc8c12bb54
8d4c3b039557d2c6c3d5bb89facd6e8e301930e2
9105 F20101123_AABSZT pooput_c_Page_106.QC.jpg
c573dd6feda6fed5638223764d0d6afc
64e2f0440c88f3120b61f8129c97c0f63c380c5e
25738 F20101123_AABSCM pooput_c_Page_100.jpg
d0ad15d256777879452b539f2a762854
d42d250f5116550a7795f4f9f56caae30ba6c371
21904 F20101123_AABRXG pooput_c_Page_077.QC.jpg
92ac7f3045b477ac22893ed3da1bd72d
469e1a9060dddbff6ec58e3276dff6b61d2efbfd
50999 F20101123_AABSBX pooput_c_Page_081.jpg
1c14623f655dc79792a63ced87130cd4
d3fc43ecd51a34d5c5bf5a97ddfaf120e4bdc3b5
19209 F20101123_AABRWR pooput_c_Page_056.QC.jpg
0e296e41564769891c56f15a3a801620
545a15d583c358c1c3c4131517196ff049331eac
25613 F20101123_AABSDA pooput_c_Page_117.jpg
8076892e3fd00556ee66c6c506f679da
45f981a454ed4ea535567c31212f9730b4adcc40
12039 F20101123_AABSZU pooput_c_Page_107.QC.jpg
ca9ed2a82d061d002068186b6016a413
1ae70c56a25393cc474c26da52ac919b5dfe5f03
28260 F20101123_AABSCN pooput_c_Page_102.jpg
92e72059b1046c04c03fd38def4c8e8b
1cab1bb9b61a481ba284b74637355e18e55f29df
81465 F20101123_AABRXH pooput_c_Page_058.jp2
1e45bfab7f2bd30bbb9feb6597432543
775363cd3a5d68f45f2015defb865d54e050d225
42949 F20101123_AABSBY pooput_c_Page_083.jpg
178147314668e95a0358a4cbfd423ebb
6979dc1e8ebf2af1394e30a23c0584e81f4eccc6
1530 F20101123_AABRWS pooput_c_Page_058.txt
cce15d58f5445ee960fb77c99c1d7d3b
99b0f5d9ac7b5ab6b8af44e5bb0fa472632a23b0
26291 F20101123_AABSDB pooput_c_Page_119.jpg
28eacd1d900c73c0c750dc31ed76e9a6
7c174e63859893dda940ec835d559fe15293ee35
16010 F20101123_AABSZV pooput_c_Page_110.QC.jpg
fedce938bf59644e82e8e045e7fbe455
fec0ab448b74673f81055a25669c010061c796ba
36807 F20101123_AABSCO pooput_c_Page_103.jpg
a7ffa8ccde722a866db859d6dc36562a
643189ec10e8717852b44318c715e595177490a8
41790 F20101123_AABRXI pooput_c_Page_017.jp2
6c611234edcc1537934e1a4262651af5
9c0a56e1d14c6b33bbac1860365c8c502f7a7ac0
50613 F20101123_AABSBZ pooput_c_Page_084.jpg
5326674fce5a28bbaab337e7904047ab
392f1e9b0cc6c9e5bc6b064c367c92c7989c53f3
1724 F20101123_AABRWT pooput_c_Page_085.txt
2727660a01411864109849b8815c13b4
5a7a0a307e45193bb9434c377ba596e10cf91a91
36039 F20101123_AABSDC pooput_c_Page_120.jpg
27881b2354befa8a378e0aa84a004352
e38fc8ac1b94c915d26f749b89ddcf77ca75d668
4617 F20101123_AABSZW pooput_c_Page_110thm.jpg
dcbd4e7e528f88f8d244e02efea86c3b
fa8316fb7a4d80856b5404458c2e56eb8f308a1e
24502 F20101123_AABSCP pooput_c_Page_104.jpg
4525b7d4a7cb7bb10d79d5367f985955
54824bc7db43d06b10ef3a5d8a8937ea16e65875
52031 F20101123_AABRXJ pooput_c_Page_135.pro
e28c9fb7d8d024fd7389e29105cc3af0
ce6081286334e6151252077235d0673594422a62
83108 F20101123_AABRWU pooput_c_Page_066.jp2
3b55c9296647c9a1a69b94d360735fc4
033f9ea227f1966078f733a85f935d7faaad51bd
26405 F20101123_AABSDD pooput_c_Page_121.jpg
0759c44eff1abb25ae680c0a34c06373
f8aceb91593722298b0082cdfd9da2217bf01453
9430 F20101123_AABSZX pooput_c_Page_111.QC.jpg
b54e3470fb6f7f9715ffddd243364209
e0c2be7b1164d025eb48831b3c91a2550da6146a
37863 F20101123_AABSCQ pooput_c_Page_105.jpg
32bd641e8523a3c32e325a2340493e04
e88e5ce09b2e8696c5c1c1c6b15085bef5b45f0a
9160 F20101123_AABRXK pooput_c_Page_119.QC.jpg
cfc3451f5121cc425fab42a3c5a8c391
86ac4eafdc5900cbfeb99a2de19d3754e8a53abe
19498 F20101123_AABRWV pooput_c_Page_007.pro
ced93df1f20474d85e4fb05ac34d490d
590f59939c457b55c60276f678c86466ec1538cd
27193 F20101123_AABSDE pooput_c_Page_123.jpg
42e457678195db2315944d0a3030081c
d989f37e85d8558370e6198890dd70a2c221f580
15576 F20101123_AABSZY pooput_c_Page_112.QC.jpg
8cec685ba05afaa5c84fe1f7b1ecf01d
ef4afd5d4c51525357165982f35d62a5d356a332
35670 F20101123_AABSCR pooput_c_Page_107.jpg
fcc73fa6c50f2870b07ce61fbae63655
eff49ff82b31adc7cb622da8c7a454a411404b99
625590 F20101123_AABRXL pooput_c_Page_076.jp2
ba3594f17605e4b8c15ae672c5f401c3
df2f30e9facbeb5dd1e0bca126c174de13a5275b
F20101123_AABRWW pooput_c_Page_096.txt
ea6873b234843694fb4d28629e076331
39b8646a28cb80630723d6a06a0733626585f989
26349 F20101123_AABSDF pooput_c_Page_125.jpg
e424066d6a43239641193b607990304d
17553d1533ab4434df958078ae1c606d6f8ed4ac
11320 F20101123_AABSZZ pooput_c_Page_114.QC.jpg
0d360d18166869035ed7c0e4e2145302
ba9c5b48af732cbccbea365a88247afc6f653cb8
1491 F20101123_AABRYA pooput_c_Page_072.txt
9535144e45d933d1c5454b8b47fc681d
89057110fd05fad8a5f0076fb0bfc43495ffab8e
27146 F20101123_AABSCS pooput_c_Page_108.jpg
dffcb9feab2626fb41d5dc649c912273
dc47390a2b2d57886fca6284a84e2c4e72f07e68
9046 F20101123_AABRWX pooput_c_Page_108.QC.jpg
3c5dc8c8e017fcda3bb5e960151e6d11
d6c97a13c2d5622e40a351f54a5729a88e0e1c7d
39119 F20101123_AABSDG pooput_c_Page_126.jpg
0d80ddb43e285dca16d66667bc195333
8bcabb8be6dade29df55469aa02ec7630e71e4d5
F20101123_AABRYB pooput_c_Page_026.tif
8b6b10a12a4d4aed35b671f6416636a9
5d020b33aebe6d6e497c0f11a6a955e042ec8e2d
55292 F20101123_AABSCT pooput_c_Page_109.jpg
511752fbc84be22a5b89f71b6c4b6667
d899daf8ddd00cc2c526cc8da51d295c4681e9bf
1397 F20101123_AABRXM pooput_c_Page_076.txt
5341fc7be5028ef50afe10717d458b3a
ed9c3a83d44ac70e3a87e1102e0d744e5387b359
27280 F20101123_AABRWY pooput_c_Page_044.pro
2903e9c502bc8c21e03f920df4faed49
87d97ff1c2b6fe0db2bdb93cbf101a679b716fe5
24901 F20101123_AABSDH pooput_c_Page_127.jpg
b31b923f6d8c487c6a421780f1eb2ff0
99833f67e986fec062b847f07facaaab6d81cff0
61292 F20101123_AABRYC pooput_c_Page_055.jpg
c1320a8f5801cc8306cdd259eb0ee95a
9d7ee7b99f33f2060f8a7856a9bc4e20f011bf40
48757 F20101123_AABSCU pooput_c_Page_110.jpg
a94c825bfa77c09c8f2d393857ef86ab
00ce0862bb998ac9286201996d9b775d437574fc
288639 F20101123_AABRXN pooput_c_Page_131.jp2
d10b710239cc0c751bb1c14cdfdd6c30
069950f471bab52a780559cf49c6d62261177899
15841 F20101123_AABRWZ pooput_c_Page_084.QC.jpg
ec414a6dde7c37ea6e0afd2ab711347a
efa7ec515a0688a9bb38cd83dacab62d31d9b806
36119 F20101123_AABSDI pooput_c_Page_128.jpg
c24d1570ec51d501cf102af5bf1f174b
30fe6ab9451fa91ddb7b4acfdf1dc272df44267a
F20101123_AABRYD pooput_c_Page_040.tif
d6c5f9e5d781247dea4876bb256dfd6a
5fceb6fa54a1f349ebe64b0e6c03f7894c1f8819
29947 F20101123_AABSCV pooput_c_Page_111.jpg
0f114109968f783868a2858ce7048e5f
5f62f166969b167191dffcfbdd1f0109f5ef3dbc
966 F20101123_AABRXO pooput_c_Page_098.txt
3d5a822fc7f6a1b6d530a0e3da5cfa20
897e19a50c79529ef65a3ab2ea4475e2e9390701
38615 F20101123_AABSDJ pooput_c_Page_130.jpg
94948032014659f4bb1249ee1162a223
cb1fe09022e5afd0f1d82d64342c121232014873
F20101123_AABRYE pooput_c_Page_006.tif
a0ab72a621fa0ad9d226e02c62a8aa8e
1448f9e2ee6bc68f97926886ee9f3fd0e7897a9b
4965 F20101123_AABRXP pooput_c_Page_016thm.jpg
178d7e433b809c468aeb179ef91da58f
643c18606e117f728f222c61f8357388c6bcfb52
57887 F20101123_AABSDK pooput_c_Page_132.jpg
8939dffcc5bf4c0e2b2f7f9d255e354a
3043b21f8712a7a088f0f2aa9420d1904e256c6f
1732 F20101123_AABRYF pooput_c_Page_088.txt
d963defb814adf3611e0644c5eae26e4
b3b89063227ac5697bd0db491f52291d527c8865
50000 F20101123_AABSCW pooput_c_Page_112.jpg
40cadcc5ef20dcc478d819afc06c2fe9
9f9ac3f1123bb426f7bb1abbd38ce86eee369c9a
4544 F20101123_AABRXQ pooput_c_Page_029thm.jpg
c14a6a7e4e1d2ac26071f12861445f19
72985b7bc573e040b325ae859bba61be6f491ed0
56438 F20101123_AABSDL pooput_c_Page_133.jpg
495a6243c673018a001242aaf416890e
27124f26e32f398995483ebc50b585f70d87bb9a
9682 F20101123_AABRYG pooput_c_Page_113.QC.jpg
cf121c86142f9589fa130b7023d04bbd
59bfed3f7eb90fbb5edc3897030c953ee12e98c4
29618 F20101123_AABSCX pooput_c_Page_113.jpg
b596e8400e412240f1b8f568ac34e288
f87a12d8d8c321968af7a9c7ec9b47d653ad1aba
F20101123_AABRXR pooput_c_Page_101.txt
76af9c53aa77b153facb18e12da62455
946b496eda65764de70e7dbaf2a0d0361fdf21a1
1051984 F20101123_AABSEA pooput_c_Page_013.jp2
16f105f003d46ac82077015888428751
d30f4740e38df1c1483f7f2ab093398e72642d2d
75975 F20101123_AABSDM pooput_c_Page_134.jpg
4b75c065cd4175ddb0079e63a8e17c08
ead824a793eaf1515e151f6198ff615fbc463a8b
5769 F20101123_AABRYH pooput_c_Page_025thm.jpg
2357a3c874e7763494fbaa35c696ba42
51177431eb6d78b0f7cc5eefea8cb85a9fd8c153
33731 F20101123_AABSCY pooput_c_Page_114.jpg
c1eab53f72ed4167af866e8f979ff816
4f408a6efeedd366a427f939eb419d126095d86b
60739 F20101123_AABRXS pooput_c_Page_050.jpg
f4b7b91377f08283182006da0455b8d5
2a05661e076843fc0bef7b1d3818226c240de81c
F20101123_AABSEB pooput_c_Page_014.jp2
bdde4a2c923d97bb98d62da6f9c8f554
4fbe375829658d708444c16f56335cdf3469923f
74557 F20101123_AABSDN pooput_c_Page_135.jpg
36f6f82c05f1f6fe1cc4e93d09a483da
c22b83a8c5d606262ad23db18b80b38a44f5fa63
25941 F20101123_AABSCZ pooput_c_Page_115.jpg
f72e9f71fea236e77e1c538baeea274f
b6f7594391a098a248be837deadcd467da789400
F20101123_AABRXT pooput_c_Page_129.tif
84b63247a87d9de6efb09a0977920764
9eec03c7881800e7aebbe2a59b04622cc0a08184
180309 F20101123_AABSEC pooput_c_Page_015.jp2
538e93a7c7373c202b801ebe1602d2a5
d82d6acd96d19a906927a3ad89f4ad4530e0cb0b
72625 F20101123_AABSDO pooput_c_Page_137.jpg
fa4e8853992560ee63d746c9f8baff1d
e0eb022388f1659a50a793d5535321245cf5fdb3
1865 F20101123_AABRYI pooput_c_Page_062.txt
4f97af08d5fcba0b6b70137fba06770e
7dc067b09baef6ddf621f30686eda39ba574d385
30486 F20101123_AABRXU pooput_c_Page_047.jp2
add2a9655faecf4b90b827825cfa3e25
784cfe6a7b38eedb3ec536b05ff8ed5ecea6ab3a
455013 F20101123_AABSED pooput_c_Page_018.jp2
534eb6a5fea60ad63f162e758166dbb7
6f7a077fa42d8f68677cdd40c7c5dbb50eeedf67
57667 F20101123_AABSDP pooput_c_Page_139.jpg
a9cbfca5d29582f8912a9d9f58a43b6e
95085e5c66b2cb6f45770604f13b606b72247330
1710 F20101123_AABRYJ pooput_c_Page_067.txt
a6287e31a55616568e7da475105cd6af
0ddacc751855897eb40f1e640763f5155fb1a696
19676 F20101123_AABRXV pooput_c_Page_054.QC.jpg
29851f1bd2042637cc06b930b8f7b35b
211c337e142823f1a040c1d040a578820c1d0f9b
83771 F20101123_AABSEE pooput_c_Page_019.jp2
40ff7b3f72794175a4c08e9aedc815dc
b72aa9cbc8a17ff6bf656fb3c33c81a24b9e7a19
22820 F20101123_AABSDQ pooput_c_Page_001.jp2
f34a0cbe5f612718fa71ca4f921a58f5
802e8256f9c78ffb0015f0574724a2f4df061408
602386 F20101123_AABRYK pooput_c_Page_092.jp2
619cb33313be59329da483d774605cb3
d3c7068a8f17d1c9dd4624e3893468025c2e101b
F20101123_AABRXW pooput_c_Page_105.tif
4ddf65fceba19869e0caf71e5fffcfe8
e202cd7b437ef656b64b3dbd10315c0b9b56c0da
76524 F20101123_AABSEF pooput_c_Page_021.jp2
6628faf6162e93f3a3621f6465e9d891
8d75d7f01c8c4a010ab60af731bd0d2365cf242a
8144 F20101123_AABSDR pooput_c_Page_002.jp2
1b691ab8e5bbbd4c358b3699a7daa90e
b4328c67125f3de5465bbab6abfa8189e65f7e16
35770 F20101123_AABRYL pooput_c_Page_040.pro
a3b6a1cf41a98e59bc6dbbf7413334e6
df482566732681d153b213a9cf6fe4f702877a5e
1829 F20101123_AABRXX pooput_c_Page_030.txt
c9a4cc99ffdab76ce5603d7ea0bda23b
7f669b3309b2fe2bf0d0f33b3a4e5a39200f3f2c
58447 F20101123_AABSEG pooput_c_Page_023.jp2
563107913dd84c6a0b79e545dbccd9ea
3b71c9982fbabdb20f46f527131a8776c9db5748
F20101123_AABRZA pooput_c_Page_128.tif
a25604e7206c6af2eb03ce4f18a124ef
12a4a6c17fc87fa5999689d455189192e9accd61
86802 F20101123_AABSDS pooput_c_Page_003.jp2
dd6332ba2c77f43423a7dba0a11f6ceb
fe02a933b38d5564505ba30dec990f5fd3a0c70d
26397 F20101123_AABRYM pooput_c_Page_084.pro
8a30b9c00d969188996cc175c744c0fa
cd398f73c9ca4e3e32e4a9c432a5938dfd7f28ac
92537 F20101123_AABRXY pooput_c_Page_022.jp2
44287876f9bfef82fd075f0cfe260ff0
737572bcedc2d8f8de44e1bca3de979a3ff344aa
64800 F20101123_AABSEH pooput_c_Page_024.jp2
1056a370306af555d40863b26a2a0adc
1a15cbfd988551dc52f9337cefe85fc84505a0ea
56719 F20101123_AABRZB pooput_c_Page_040.jpg
6d1b32f0c3178f712796b38d0230d958
e50c8116c17c4ccd78a6960815e7a642d4fc7545
1051976 F20101123_AABSDT pooput_c_Page_004.jp2
45558540c1f3c9dd13e45d48bd7e9680
6511dc32c3db794bf55656c5d29962eb18a24def
F20101123_AABRXZ pooput_c_Page_042.tif
57f1e486603ecdae03604ffc97268d5e
14a0e8f4bced2fc59c993064f22fd2be027a724c
98524 F20101123_AABSEI pooput_c_Page_026.jp2
ebf5f7620ff10157eca84f57ae036c1b
08c5dbc5eba123ec9036729cdc459d3f63cf4727
5458 F20101123_AABRZC pooput_c_Page_132thm.jpg
ff85ec84d4fd3b230fef1d9e05462366
274b715e8f094f2c3cc112738d799addb61cd2d4
1051940 F20101123_AABSDU pooput_c_Page_006.jp2
bfc9af48f93a7796e02e2c8b03ab50f8
05bf6d5f76a29e0a076b52929168c088afb1d544
16831 F20101123_AABRYN pooput_c_Page_122.pro
7e38d31d7ae7139b73eab142b5da3a59
b5b596370695571a3e630ea3727cf62e281269ab
84958 F20101123_AABSEJ pooput_c_Page_027.jp2
9eacd143c679baf029b1cb38f700d257
3f344e46b6dec6f8906cc4f751d34b7286015087
16576 F20101123_AABRZD pooput_c_Page_042.QC.jpg
14e72f8abc7a394432cb21dc4c53c4f4
c185967292f0e8a1b9484968c45a1e6f0654dc77
556886 F20101123_AABSDV pooput_c_Page_007.jp2
81f995721300f0b7581c98afc62044b7
61bf6aef1c05960e0d467535c53cff6c3f854fef
17299 F20101123_AABRYO pooput_c_Page_075.QC.jpg
08879397acd973c9d80cbb55d0af9c47
3c0006ff92d9363d40d6663b44f6bc5940212a0e
35091 F20101123_AABSEK pooput_c_Page_028.jp2
96a6ea836dcbc3b51b6b87b83d5e315c
de8b05e868a702c06456a339e9f725d0e9cae796
70579 F20101123_AABRZE pooput_c_Page_059.jp2
e8873255003e11d3cfde3b9b0a4d60af
913ef880816deeb10024adb6b989d8dda40a7ca1
1051978 F20101123_AABSDW pooput_c_Page_009.jp2
898b37bdddf47a900ff2386fdcea343e
2c05532be2252637f233c58ec1c9314f1afd9d6a
4259 F20101123_AABRYP pooput_c_Page_006.txt
a98fc5ff5deaafb5a1648d96bc2dd0ef
f6265beadde5e84df711a005f824988fadefb041
58168 F20101123_AABSEL pooput_c_Page_029.jp2
dae67ab119a106b92b420a355e6573cb
efda220b5d1037f365c6a564e236cb378a5cdd4a
294170 F20101123_AABRZF pooput_c_Page_108.jp2
e3afd86bc7b267f84603aaf4aea9b915
780464a22bff87e3f4fa2cb3930984fe69926288
1051979 F20101123_AABRYQ pooput_c_Page_008.jp2
b3f1781667d40bdd300f89b7fcffb206
620519162fafc85162d52d18445745e93863a6e9
47463 F20101123_AABSFA pooput_c_Page_049.jp2
56c3e58c036e4807609de5124cbe7cae
8e259cd4fc3b45e318e82edea73634e7ed283df6
68957 F20101123_AABSEM pooput_c_Page_030.jp2
bc78077534a19589d09d9668034e1919
335ede05d3f3e6f03a2a95aa8b6ce10bb933042d
14875 F20101123_AABRZG pooput_c_Page_010.QC.jpg
b3bd28c151278dc3c1d5769aa56e1c83
2b8f2589354de154056306c5d8437309bfcedbbc
1051977 F20101123_AABSDX pooput_c_Page_010.jp2
ace499023de3cd07c655a2fc394377b0
644f8d6f626a250d7fe5a9d9e2c8b862d7ecb681
6414 F20101123_AABRYR pooput_c_Page_051thm.jpg
6ec3a7af135ca725e7130535461fa069
8cddfa28171ed4ac38c7ab6ff93ea61bf3b9b05b
86586 F20101123_AABSFB pooput_c_Page_050.jp2
7dbd894d1c931fe4beb25103007cc369
9f21cf14f8adae66a5ddaad38e75a44224f6ea9b
91040 F20101123_AABSEN pooput_c_Page_031.jp2
0e2bff98aa66b591be3dffef37b5ab9d
84466281b7eb19ef28ab7b1910d6091ca7eae6c3
160348 F20101123_AABRZH UFE0011625_00001.mets
27ed86f63203cf51205e64bb6df4b2b6
99ce8d09537a2d657da12349e53aab7ee34bc16f
F20101123_AABSDY pooput_c_Page_011.jp2
05dc51c4b426d6ab498e89823ce34c33
9bb13e532efb9cfd3a1078519bcfcfe5d97b23b3
5700 F20101123_AABRYS pooput_c_Page_133thm.jpg
ce2d3d444c19991b3e0b4640b4a3d125
d662fbcdd3cffaeb2d0e5c3e618aa1f3b74ad647
80935 F20101123_AABSFC pooput_c_Page_052.jp2
eb34af16554f908d2150922d1089f7ca
2628f242e1d48e377b2e01367e0d8aed31098d5a
69607 F20101123_AABSEO pooput_c_Page_032.jp2
968db790b32a067feeafa514791cc16f
a308ac45576e524b88ad3c9f3b2ce646320d204c
1044601 F20101123_AABSDZ pooput_c_Page_012.jp2
bd13214cb3c845c88501e06bea0b64fa
2dd9474138be9ee9ece19df6af76c76cb7098574
1596 F20101123_AABRYT pooput_c_Page_092.txt
bf017477ec04cea1bb8403046cc059e9
96a006d02f7181b75f22e97b70f76e69786ff545
99216 F20101123_AABSFD pooput_c_Page_053.jp2
58d948085081781dcfe2c65f85670983
fb10dc1f5ec8b5e91963bb73be9032065eedb838
69711 F20101123_AABSEP pooput_c_Page_034.jp2
5e73a583762b6a47096879c3dbcb0c67
f665d677362f6841fb24f799ce6f4dc07b03c144
1489 F20101123_AABRYU pooput_c_Page_052.txt
faf7a71a76c9036f88b3d8c3f70bd4f6
f9f177610d4fb64076c298f04df135f20cc20a7c
82120 F20101123_AABSFE pooput_c_Page_055.jp2
c7b17ce66fb72e566223c7995f0c807b
53eba6c2a277a0d9970a2eb5088ca11f8f1aaa5e
103828 F20101123_AABSEQ pooput_c_Page_035.jp2
57054ecdbbdf6669e290bb3077432a2f
03a93cad40b124317d82aba85691b5c7a8370e12
11054 F20101123_AABRZK pooput_c_Page_002.jpg
ae99386b2c8f3d3eeed4fa2bc99142be
967688fe0d53493311aaa44c69c9abc37d4c0533
4911 F20101123_AABRYV pooput_c_Page_023thm.jpg
bcc4f8df7dfdd0b04d4b6218f30f815e
609a313afdf4a36b5b9b3a77c63544ed8ddc2fa7
81937 F20101123_AABSER pooput_c_Page_036.jp2
72375f22435e13289572015d02b81d11
0a5d5d3022ad44122c200a152c6213e3eb210010
60153 F20101123_AABRZL pooput_c_Page_003.jpg
af80870fdedd467d8647ed4bee6bde36
3755b685cb70a280852a9ac586462c1609064fbc
F20101123_AABRYW pooput_c_Page_120.tif
3bb103f1a6d84308cce9ba25bf0a16cd
1fe17180ce4b35da0175c30e898d3d24369005e7
74958 F20101123_AABSFF pooput_c_Page_056.jp2
5df21a67c667d4136db88dccb1dcf210
22cd74fb2e81031296fa6e1b88a24a6d8f9ac0d7
104637 F20101123_AABSES pooput_c_Page_037.jp2
12174c4ef2d302b730baffcabbe1ec3d
df306172ce1509a2399c97748e9ffa1f96be2a69
67533 F20101123_AABRZM pooput_c_Page_004.jpg
870d7882ae0ed331d99364a9532a6b34
d0b486d6084e4b637f2a67f40a494b7d2aa289ed
3319 F20101123_AABRYX pooput_c_Page_125thm.jpg
0e4ffc47668477d468db3cad65757f86
dffc8b123d4cc434cdeafe31d3c63423e9b5dcf8
98846 F20101123_AABSFG pooput_c_Page_057.jp2
1faac572587bcb423ed91644307d4800
b6b28cdd47b5498d636a779337b8ce146c76196d
84941 F20101123_AABSET pooput_c_Page_039.jp2
5fe3ae75aa3a8274a390c591141edcdc
518cef13ab5ce695135a78d747a4ba2ff613ad20
101746 F20101123_AABRZN pooput_c_Page_005.jpg
b1dbf2e2c889fcfb53034d4f87bd7f64
b0833289a26ad9aa2301c9fcae7e6deb78ee36d6
70742 F20101123_AABRYY pooput_c_Page_014.pro
d1615068aa7e478b5a6a02dda9548906
ccb60e0b5b692e90fc86dc8119f1af9bb0265b14
35422 F20101123_AABSFH pooput_c_Page_060.jp2
e15322e9438be3fc03d80bfa3665a185
8269daeb8614df70dca0d12bbe4874bb9214fcf5
79208 F20101123_AABSEU pooput_c_Page_040.jp2
cbf30f53653a9733393d0c7916697fde
9e0593fca01e1f10285154ea505e4fddd9bb3b82
36681 F20101123_AABRYZ pooput_c_Page_025.pro
5806eeca5de7c2251ca103a3ea7df0d1
1ba9f8c24a91b69d6bdc323948365e7a7ae60cbc
59119 F20101123_AABSFI pooput_c_Page_061.jp2
ac7819f4b0b8e168216ae2a32e8a09cf
a177cb2b28fd7c8dbbbd42c177e01e32db1e4527
20667 F20101123_AABSEV pooput_c_Page_041.jp2
2186bc100a9f012ace11e846f71c8920
3006647fb37385cddc3978305d3dac4c05affbc3
97276 F20101123_AABRZO pooput_c_Page_006.jpg
0ee8bbb0d2b3632ee2c1144d2ebfc1b0
f6a6efd886330da3785ee483ae3a5d5007dff1db
86895 F20101123_AABSFJ pooput_c_Page_062.jp2
194870a1d22e14af96edd10346be63e0
9735c1a167634387d5fdfd43b51060bc943869b3
73134 F20101123_AABSEW pooput_c_Page_042.jp2
70ee40b3660cff561962a17c163262ab
7b89dde63f02f90194764337477cf67d777ea5c7
26354 F20101123_AABRZP pooput_c_Page_007.jpg
36c2f6472f708a64f07bf4b47b4fc26a
da21df729abdeb4593faaf00bf930252db3636ee
67259 F20101123_AABSFK pooput_c_Page_064.jp2
7a284ba7c7177c51717ddfae4002bf7f
70a18b1a7bdf6f76c4557ccbdf04bb6d9568946b
80404 F20101123_AABSEX pooput_c_Page_043.jp2
cf19e9c89367930ecdbcb56231015106
95510c3b4bb6c5a23a8508db8a8c75c7c3c36edb
65865 F20101123_AABRZQ pooput_c_Page_008.jpg
4fdfa855472a1f4660ee25b7918feeaf
b9202fc0c4f2e1ae3808612c614c4e2574f0f3a2
100877 F20101123_AABSFL pooput_c_Page_065.jp2
0e14882389b43e2a7a83c230ae00d731
f26d0872a168f2f477b9b0cf6f5a3be003d9a924
51023 F20101123_AABRZR pooput_c_Page_010.jpg
4ce4417559c3e7cff612aab94ec8c6e6
35273fb4b4d64e7d0365b8652a9aca9925f20e8c
76689 F20101123_AABSGA pooput_c_Page_086.jp2
46421e62a6956628f0bbb3e869bdbf0a
fb1ca39ed0154702e630af92d576e9bd00a6a20c
58470 F20101123_AABSFM pooput_c_Page_070.jp2
f89a285bf4abc3c12a5c2fdd29b590db
fdbbff6236b2476d57e1fc344e3c7a82cc0bbbb9
60329 F20101123_AABSEY pooput_c_Page_044.jp2
bfa9fb5c2e7b8276f86d77cf565f45d9
55886b3b2ae06705da5439a61a18d90bac086863
81552 F20101123_AABRZS pooput_c_Page_011.jpg
a7321ac63da28006188ce460c7d5f42f
9a2b6fe7b616332ae639615974d8b6b2bc05c9f2
70089 F20101123_AABSGB pooput_c_Page_087.jp2
2402caae185a74bdfdafbf29dd86cf09
aefaf0a3749cbfcc19a5b5653126e13a8521022d
68519 F20101123_AABSFN pooput_c_Page_071.jp2
5bd4c0753089de50a9292f6aaaf507a5
c9837620e1ab3b2af9cd669a418905fb97212b51
74441 F20101123_AABSEZ pooput_c_Page_048.jp2
cf1b9172daa3604f0af1cd8a9791d586
f509d78aca1332d1d0c1fb14260db30c443bd04d
71642 F20101123_AABRZT pooput_c_Page_013.jpg
82ed6076111f11fdc1052b0597d4338b
0cee9bba50f8324ec0df93f9371df23297fb6270
75791 F20101123_AABSGC pooput_c_Page_088.jp2
869940a5cd8aa37bd7b6aab89bd774bc
8331c28fd8b163870085da1414ea61466aea709c
91335 F20101123_AABSFO pooput_c_Page_073.jp2
829e277898ab77898373c4886be740b4
022e909ff239e183317360c7443e20ef16721dfe
80423 F20101123_AABRZU pooput_c_Page_014.jpg
635ca5c6fb2a19ae299da5dbd432120e
f8160c69c64b72a3c4b9d4588a03ed3c1c24bb94
750072 F20101123_AABSGD pooput_c_Page_093.jp2
6132e0b3304f5178da3a28e6637ef732
60b116fccdab1e38e21b7db0d97c9a483358289c
677938 F20101123_AABSFP pooput_c_Page_074.jp2
b2b3384e46de7de77d745211d915a0b7
c737df095d901f97aafed3733e469b2301c4405f
13540 F20101123_AABRZV pooput_c_Page_015.jpg
cef8c5e570bbb59f509fb7ee43b12ff6
b187555ba563f534b12482abab9d2ae72dbb60dd
58990 F20101123_AABSGE pooput_c_Page_094.jp2
3de82cd6c5de36030c870c93ef0546a5
0a172a1d239cb9f0c2c047d5ae5815b75d50aafd
776704 F20101123_AABSFQ pooput_c_Page_075.jp2
6d3defc57b46fd322f0868d695632f9b
634bf13e9036a2a3798ff5d8fd37a05283953577
54699 F20101123_AABRZW pooput_c_Page_016.jpg
682820d3b45e2b3595378f819434d610
29260a2948d386843d93560af5532810679043cb
313932 F20101123_AABSGF pooput_c_Page_096.jp2
42a3bd74bddbf2d620d20016b3a21c19
35c35c9c271110d9eead5b2eb1f0807a5c77039d
97136 F20101123_AABSFR pooput_c_Page_077.jp2
9b0a7fd621c388d9c9ef322d0e2cbf46
842f428545e07a742d65100d5597df8af2c7ba7d
31176 F20101123_AABRZX pooput_c_Page_017.jpg
21a555dba6ae226d1d3c6be31422a373
d14748f6a346e09058fc071237f63cc6e2aebb46
91776 F20101123_AABSGG pooput_c_Page_097.jp2
fff7409e9c74ba9472172cf087b6f69f
0f62bb881fceaa36b196760b777ce02463d4f349
95912 F20101123_AABSFS pooput_c_Page_078.jp2
5cc4e75bddd4765df35c939528842484
7fd4aa7e7a50a9524d2796b3a6c858bb7744ba69
36182 F20101123_AABRZY pooput_c_Page_018.jpg
941b5f494f2d8c9919fa0fd6bd151675
24e300775f6e2f28125786bd11041d9dbadfc282
55591 F20101123_AABSGH pooput_c_Page_098.jp2
1356534e786a4831b77d5b7ef6ff6289
781cc0464ba7b13efe2e191260cadfd33d3beeba
33546 F20101123_AABSFT pooput_c_Page_079.jp2
00f1518a1c0fc4b0e123188c16237dfc
6072b31dcf880f03b46e4397f67978ec6a06c325
57382 F20101123_AABRZZ pooput_c_Page_019.jpg
97f7441650788e26c1780aa4be5d9370
bf596b4d1682b3e59cbe975348da3882cec6e4bd
46208 F20101123_AABSGI pooput_c_Page_099.jp2
f5bb0d330ba209f2599699e6b7cf6f28
63c8b8ed69e89b7ccd4e11b83fd3e095e1fc29c5
93664 F20101123_AABSFU pooput_c_Page_080.jp2
7f123115f2899b645feb4b8199aaa80a
7cfa97fadcf2e4c8db28b9cd44b5681bc33a2ba4
278431 F20101123_AABSGJ pooput_c_Page_100.jp2
38ae623e4426e8d62877506ed10bfd98
aeafcfffb3777f019c6c152ac2923c62da990e01
73653 F20101123_AABSFV pooput_c_Page_081.jp2
53d480722cbf9305925b1a275a73838a
f576961b8d4f4e8c2598da4b68224b87fd70a931
37287 F20101123_AABSGK pooput_c_Page_101.jp2
5e27fbe5aaa0d3df48d536450b156267
c7fe354146a54251f86a00906fac8cb456d3c41a
67638 F20101123_AABSFW pooput_c_Page_082.jp2
47f5a761714e457d29307dc5e9dff287
afe12114d4f5a387b3cd1812ff6204e0ad10f6b3
286892 F20101123_AABSGL pooput_c_Page_102.jp2
49307d1d9c3f42c18173e2e00b7cf61d
7a87ad2639eb8fb47525a3dac7fde69687e95835
59853 F20101123_AABSFX pooput_c_Page_083.jp2
37344a226f7506823d62da21a54aa2a2
d3eb6f30e191810d71be21a2279beba4732a4154
285005 F20101123_AABSHA pooput_c_Page_121.jp2
07115e5607f68b25e813bd8ba97567e5
30ed35fcd1bfb4a81ed95d3e4c8e4eea54374e80
259904 F20101123_AABSGM pooput_c_Page_104.jp2
5256d1c3a0f115e4c3b7dc991e3722e1
96dc9377a025a54d7265de1f4bd5cc3ccc9b3ffd
661867 F20101123_AABSFY pooput_c_Page_084.jp2
cabe7685e18cf069713eddd4913a4a1e
fc7c85e0a96b2c84276e17ba2deb4dc714549369
276344 F20101123_AABSHB pooput_c_Page_125.jp2
7df967137fd30cc3138feaa5f868c742
3095418e932ba540acc03a75179654373460bd6d
35791 F20101123_AABSGN pooput_c_Page_105.jp2
1b40ebef686e98fa97beb0253cb7dca9
64d7af32d2306b48325623b679c2296477802169
34681 F20101123_AABSHC pooput_c_Page_128.jp2
69b180f59c181f998058e85c75fb81d9
b9882f606d3ff4711603fa4f9a54b2cc08561443
282749 F20101123_AABSGO pooput_c_Page_106.jp2
0b60dee76a24d1db9901370f156e3743
b373749303495263d939e5d961b30b96cfcd3b7e
80695 F20101123_AABSFZ pooput_c_Page_085.jp2
89d4dd2f372aea7376cf496bdc54713a
141fc32174c0bdcafc2ac5dd5934b213e2359557
284701 F20101123_AABSHD pooput_c_Page_129.jp2
423eed9993f4750033417e1f28e4ecc1
d8ba2fe4197e445d43a1aabf3dd0031cb2bec21a
34868 F20101123_AABSGP pooput_c_Page_107.jp2
db26a3dca0bf42942b642f2a2567e9d8
bda0ad1726917d7cc71e61919e5ff42bfabba21c
37094 F20101123_AABSHE pooput_c_Page_130.jp2
8bb85cd83c3b5191d40d5b974ad3f7f7
b9b50011a19b2e8f4a66fe94d40183f2498168b1
70531 F20101123_AABSGQ pooput_c_Page_110.jp2
17e20c186961c5bc62865a854a8828df
cd22d7d954459cfe610529494a94a77e00099c7a
84919 F20101123_AABSHF pooput_c_Page_132.jp2
428c8ffb4345050946c6ba198b8ceacf
93aece95f06fb651f4a467913992d45a21f5f093
72606 F20101123_AABSGR pooput_c_Page_112.jp2
06d054e41adc10a7ecaf9655c1b6dd20
66091a643505942a12d7d5501d7a1d6090e95e85
80147 F20101123_AABSHG pooput_c_Page_133.jp2
f6477717ad48373de15a7b9ecb5b8030
c68107c1d39e4af4b72ac6e45550c42258ade4cc
37266 F20101123_AABSGS pooput_c_Page_113.jp2
eae1cbd82d3f4f861fd8dc4aca4a7bc6
438a469ce0397b8ef4068e7bbea0095cd261b7b4
110970 F20101123_AABSHH pooput_c_Page_134.jp2
8d67e302ac7456bf13a66547dc8e7d16
c59f8f730963dd3045c7fef5987af8c300b3565d
32421 F20101123_AABSGT pooput_c_Page_114.jp2
73f11c017c364e813687bc9df13ec7e9
c52ac891904e148b435a7c78431d6fc3826d6510
110273 F20101123_AABSHI pooput_c_Page_135.jp2
396c4c91bb289c9c5257f81e05fa5f44
4a1687a79a94e2b0c88e3976a9bf774c6068c9ba
282194 F20101123_AABSGU pooput_c_Page_115.jp2
ece54947d77f7331b89714427134ee2c
e460dc6c5f7ae3f843eedfb6949e590ccc14f945
112173 F20101123_AABSHJ pooput_c_Page_136.jp2
dd13fd26233b45a73e77a0ef23cd7bf6
7c0cb6b48d3f3bd5d4008535618ea7b7979afbd6
39073 F20101123_AABSGV pooput_c_Page_116.jp2
4005c98e05ea8f5c174f5577cf3d2303
483ac477a155509cf8d7c7c1e78ea13853a6e4fc
996275 F20101123_AABSHK pooput_c_Page_137.jp2
d8c3be1525be635f96eec217d882d9a0
bcd3ba49c970b2010a86d6869920d88343082916
283892 F20101123_AABSGW pooput_c_Page_117.jp2
c957c63ae94c9d90667cac9b6a695617
97a0ecf0cbe89b8c73332cba89747f5062961ad6
32922 F20101123_AABSHL pooput_c_Page_138.jp2
791898cb0a1cde04004da3c8f6123ebb
c72ebd58c2f63f2741ca1f9caa8a15aa13262dc6
38210 F20101123_AABSGX pooput_c_Page_118.jp2
76f50560b12d13ef1ca182482c27de7c
ff5ae44a01e95223709af2a50913e6891b0145ac
83054 F20101123_AABSHM pooput_c_Page_139.jp2
25b9500cd48ec65f35edc66575848068
82a930daf5c1dcebb3f677dda13cb7a894ba80c8
281984 F20101123_AABSGY pooput_c_Page_119.jp2
5b9150173551bf05cfef0cac38f543d2
1c8cc2abe50cd903d3400364cc9b24209bb53d86
F20101123_AABSIA pooput_c_Page_019.tif
aef7776ec22165b0da444f14ef7bccbb
d9820c9ebcefa2531f83fba806bebacf0c185ae6
F20101123_AABSHN pooput_c_Page_001.tif
a31381c47e53cddd824324b083041f26
edfa79edafc4b99e040d8f42fa58e3fd123645d3
34367 F20101123_AABSGZ pooput_c_Page_120.jp2
72bde6250e26e5e67441cf225f127fcd
2a55c33f87b3f13ff04809d86d6118964c7ae927
F20101123_AABSIB pooput_c_Page_020.tif
ef95aa0b3de1be0922feb31255f4c9be
8f396b09dbae5bc2ce526e6a86dc4a386810d2fa
F20101123_AABSHO pooput_c_Page_002.tif
f2ca4849e0a4ae59f5b59a2e244d27e6
81727492caf6b1f6266c6a4c29effe76eafd1d81
F20101123_AABSIC pooput_c_Page_021.tif
7fb81bf34c13d1acc2dfdab88c774cba
ea63b141aebdacbbabf295897356fded2a48a8d1
F20101123_AABSHP pooput_c_Page_004.tif
5e4113cec23eb8f94ecaefeae9ec3fe4
0ca6800e67552c7160f6146e25e6d634b0997444
F20101123_AABSID pooput_c_Page_023.tif
ebcd2980dd6610f9d93f2dfb4df0c12e
194744142f4885e982a6ede20b3899988deb9173
F20101123_AABSHQ pooput_c_Page_005.tif
0d69c0961b8cc2bd0393e7f3002f3831
46a9bc1f63ddbea58cbf887f2fc40ceaa620a11f
F20101123_AABSIE pooput_c_Page_024.tif
d3b5e061a5910f2215b47e1e599f3ad7
5781fa27d45712ba0bacf13f39f8f62ff8625c6a
F20101123_AABSHR pooput_c_Page_007.tif
19b88d5f8de18a169e3423b52fdd7f09
3b7ff30a6abab6f27ed634b2dbe0acefbceb5565
F20101123_AABSIF pooput_c_Page_027.tif
5f11c1691703adc9ad9c34db69d01046
77f0d0cf036a4c5c49bc105e99a505c69cced6a3
F20101123_AABSHS pooput_c_Page_008.tif
54f9551575ea673241d46d76256be88c
a26fe23e84533fcc32cd0ddf1bfa1a21807b5a28
F20101123_AABSIG pooput_c_Page_028.tif
4a5f69f4d41000756d44ac9694f40989
9e225f7bc5f85f87670be67139025ac353bdcbdf
F20101123_AABSHT pooput_c_Page_009.tif
3b71b165a2b5a87987b5de89f5e6009d
a5c4dd36b29eb34780d814e249e4cd048e66b3cc
F20101123_AABSIH pooput_c_Page_030.tif
7df344bc61ab584c679bb69215d8b42e
2da5eab5fc6b804772cff38b48aea3a0ad6954a4
F20101123_AABSHU pooput_c_Page_012.tif
59f232435882d36f8f9cf7a192be171f
3893d0b40c6d852c232eaf5f6302dfb9f08d0166
F20101123_AABSII pooput_c_Page_031.tif
cde838807a22b28b5b900837162fa3df
6dd4ef0506d19f437194738aa9ad998a78d5a412
F20101123_AABSHV pooput_c_Page_013.tif
703ba275857db66b66e5c0308c4ee213
d2f6cca01f8622101ad531945011f2d9f3cd4237
F20101123_AABSIJ pooput_c_Page_032.tif
363591fd109c494b4a8bf5bc3605f599
1a07e303784a60c132737e7138f38edaaf17c16f
F20101123_AABSHW pooput_c_Page_014.tif
2f2f2d37125533297e4ceb14624c6e29
2a2813ea72be8f6667979dfdcda6e79e0fffff43
F20101123_AABSIK pooput_c_Page_033.tif
754d36d11b17beae4fffa92c5583ad1e
9f1efa970696d050d6483bd0bca9c844e3003846
F20101123_AABSHX pooput_c_Page_015.tif
0c869707d562b995d57a464972fa1377
33696ae1027b552d147e23d5c6510ae8519e3d51
F20101123_AABSIL pooput_c_Page_034.tif
5b98f8c9c7bac9289080dc5a0cc129db
1680b8c30493cba9c880b205436610a284349d77
F20101123_AABSHY pooput_c_Page_016.tif
c02f4dd77b59390a58b2c2548dad99da
2e619ba581c84e5b9d0c7d537edfcaeef0bbef8c
F20101123_AABSJA pooput_c_Page_053.tif
985f68c2c65c4f0c4a97f658dea275b9
d64e50b57245758b29be08233be5ae57f1084d82
F20101123_AABSIM pooput_c_Page_035.tif
54b2dd81017cd5391c1f88ba66ac9641
57c764dcd1677c9b92ec7bd7625eb965583ed85c
F20101123_AABSHZ pooput_c_Page_017.tif
7a7cff0e02684df2aa334d80dd5cdcdf
535e159598a0e059839c2b6a03609c80e36b56bd
F20101123_AABSJB pooput_c_Page_054.tif
b9286fa63da2a24b3effae8832091848
08f975802b550b29d7f679805680c13232ad792d
F20101123_AABSIN pooput_c_Page_036.tif
6cbdec5df095da0caeefb8871d495e40
bd2ecbaaaa534efa911d6ef28670029d0abea101
F20101123_AABSJC pooput_c_Page_055.tif
e70bff8255b47ad14b831b4a3a583bd1
f40cfcf891d349e967acf24337cc30d9518fa5f5
F20101123_AABSIO pooput_c_Page_037.tif
ab3b9e7e6afdeec0cea11c7c12502944
d0aff99255aa7da56ee10103d5aa589ddc635f56
F20101123_AABSJD pooput_c_Page_056.tif
4d609e71a13baa200bdb07ef879dd597
062d1197e4fae4110532bb8212910ab4b1e09c64
F20101123_AABSIP pooput_c_Page_038.tif
281c06af2dcb4ba4ed9cf70917f171e7
2c9cdbaa234db00c5a11ad85fdf7d73a34e9bc1c
F20101123_AABSJE pooput_c_Page_057.tif
c49fbdfc03c4c9875021eecbc4e6807e
cb4f09128eadbb25d12944acc933f7ce7e06ffad
F20101123_AABSIQ pooput_c_Page_039.tif
5afa39f7242754591564ef66e3f49415
efe3dd8d6ba8422b830dffe34ddc1a1d832d5e89
F20101123_AABSJF pooput_c_Page_058.tif
7141013dff9279d65c4e600b61f8e9e7
f8a271b6c620b2964388270d6084ca13bc983ed5
F20101123_AABSIR pooput_c_Page_043.tif
8bedafb486af627a2c4b2133a401c2a3
d81196dcc938e5c77ce86d49d68a25dc952da437
F20101123_AABSJG pooput_c_Page_059.tif
1397cf39a09cf127309ecf38e249cb7a
5254b32cced41e65b926ed7deddb8ec2f9d2c0f6
F20101123_AABSIS pooput_c_Page_044.tif
10d36f8e236c94a67851ac00b83aa489
16b06eed3f17a4d6b5b4cd1a3b5bcc3bff8616b2
F20101123_AABSJH pooput_c_Page_061.tif
47cbd0519e4f6345fa7b27ca866cf068
ad781f5443c40db68f2d325e8bad1734b3ee2f9e
F20101123_AABSIT pooput_c_Page_045.tif
be1cc6c0a225b48873b95f9fbc6b2eb8
e464664e433ced2146b467a81901078bfe2deef3
F20101123_AABSJI pooput_c_Page_064.tif
491b85e2257d53a28dfba2794871dfc2
f4d50c7d42376f70bce7935638263644ecac48a7
F20101123_AABSIU pooput_c_Page_046.tif
66d4dd04a0b2417294341390b407ff4a
1fdecb4cb4bf35a204f00b4e10f640d011e4ef79
F20101123_AABSJJ pooput_c_Page_066.tif
ca00aba678f37be6699d15e9dd07a475
e5a7a88bce2d8414d5de51fcf19090edc3829870
F20101123_AABSIV pooput_c_Page_047.tif
e5509c6d705d291be246b6022fe90570
9a35cb5ceb138da5e9720ae80c5c0da9a0a902d0
F20101123_AABSJK pooput_c_Page_067.tif
42a5627242c79ed7cec40c9059a240b4
65d88862c2333c58014e9fcef7fe1d80758fbce2
F20101123_AABSIW pooput_c_Page_048.tif
28815799687641621f5729c9fe7ca18c
b0c7c8e4d64f9394ff3e76ec12a5f20e9e20336c
F20101123_AABSJL pooput_c_Page_068.tif
a1816be29a41e66f15978684efe90349
a195330aee59dfdd04223f47ffd6a30867113c33
F20101123_AABSIX pooput_c_Page_050.tif
be7f0481694cfa1a2aef7af579422d37
38602557328520a68ab851d1e5dbb4ff7e34a18a
F20101123_AABSKA pooput_c_Page_087.tif
ea33d4b798625bcefffe010e5427f5b4
823521dfc7473a3c3ee428af6839c9418a235cc7
F20101123_AABSJM pooput_c_Page_069.tif
fa03b353e074e051b818d39f2ec35236
5c97fe7a8892c450b4806ae8de4e40f041b02d14
F20101123_AABSIY pooput_c_Page_051.tif
15c4ae26f6ad4c732eec4e4771669b9a
8cd691f11e0e210c3deeff344e9d37fc132a64b5
F20101123_AABSKB pooput_c_Page_088.tif
68b8e21c765d5cae34a706da947e7ae6
c2f0edc99e6acd6e26877ef9edff6e69c12ce627
F20101123_AABSJN pooput_c_Page_070.tif
595174f6095d7920310be4de87655d3e
52583daf455320c3f63d202d9ed3a2d9e3e3d893
F20101123_AABSIZ pooput_c_Page_052.tif
a606e4c01bf3d68381c5d4ccba6d9119
a98ef7825fabc618a3bec48a6dc734c45fa9d8fb
F20101123_AABSJO pooput_c_Page_071.tif
7d51a5a1049dd819ccf9334ee33518a3
33a4f1000731798a2dcc61b5e7f9bdd1cd491113
F20101123_AABSKC pooput_c_Page_089.tif
b8f43559480d7df44c3c23c8bd7bfdd0
743e51706c761bbaaa24ff1ae3317868868866a3
F20101123_AABSJP pooput_c_Page_073.tif
0799d07f1c1606358d1127328e89038f
7e1641e9205796377b3d94c977123174aa38cdde
F20101123_AABSKD pooput_c_Page_091.tif
056686b00d023682d060de9cbf1c524e
88f885b4dd04fd434dcce3675e9fd7cb7def33e3
F20101123_AABSJQ pooput_c_Page_074.tif
6bdb27f98f37e17832fd0d41353daef2
657bf7609950b466b31610177346ff6a00f853f9
F20101123_AABSKE pooput_c_Page_092.tif
76c0282e4f6d4d9dfac66976256dbc89
407efb61a6b4b7691bd3416378a90bef1548ccec
F20101123_AABSJR pooput_c_Page_075.tif
f18c8f1edda7055d4b72551e91318861
0acd22cd1b1ac2f0efecf24b08fe6d0dfb96c6f0
F20101123_AABSKF pooput_c_Page_095.tif
be2b725af03ad277600d47c905f7be95
e880b5ec23cf78bd6ddab23c2ee8840f48a3586a
F20101123_AABSJS pooput_c_Page_076.tif
0e06d18df2362074dd77004694f966da
e73fc2bb395711537d8dbdda1430de7ff254177a
F20101123_AABSKG pooput_c_Page_096.tif
3c1467a0e5435d3bd13d79833ecb21d4
6a9b48183ecf95048855dc103f31bfcdf2b1aa6d
F20101123_AABSJT pooput_c_Page_077.tif
739de68fe521fc63bda16df8e9e10be5
4dba94b9d3ed8cde524b8f2ea6a3ab3392a53c5a
F20101123_AABSKH pooput_c_Page_097.tif
8f3a7e5bb896c522bfb034d6ff96e90b
ac80d8e30a0b003fa2ec47bcf6efb6d16309b442
F20101123_AABSJU pooput_c_Page_078.tif
04db47b202efed6cae8863e561456457
d4b75afb0b815a6794e16d23d38ab2a6cd9e24a5
F20101123_AABSKI pooput_c_Page_100.tif
45981ee9ecfe8ca2c15b41a3ad3bc8a5
d9736ba5992f888b0a258d3eaf18036d1f42f8b9
F20101123_AABSJV pooput_c_Page_079.tif
1546fc234aca41a45fd727d1c32ba8a7
b887fca664bf2953fd243432901b22da5d279a0f
F20101123_AABSKJ pooput_c_Page_101.tif
543b3b98499d37a754e6b40a08305297
b2cb95836b76b7165c0040fcc3ba55814ca13f2b
F20101123_AABSJW pooput_c_Page_081.tif
bd2ce72a7c98f8fc9fb3932e6e5d6ca4
764cc06a7f8d1a2321c63494648a2bdc8af49956
F20101123_AABSKK pooput_c_Page_102.tif
849b626fe88a9f7ecc2512d258433948
66c8313bebff168e25442be5db8ebe5793e7f5a0
F20101123_AABSJX pooput_c_Page_082.tif
deb63419a14c686fe02d0a002db27e10
e626adba43bc8004ad6c591b5e6ba5281e09593c
F20101123_AABSKL pooput_c_Page_103.tif
5f8b3973e9b4ad777aa5e5b045821e02
76d4e435a4cbd30fc99bd942122045a6a89074fe
F20101123_AABSJY pooput_c_Page_083.tif
f8ae9063d8af8a2c5f4446a469c8992a
bad472f1c583bd48a9f0dd4463c8b2130d145711
F20101123_AABSLA pooput_c_Page_122.tif
194969b4e5a05bed62b9d270cdd83c17
c3fa97ac72c707d77191fda9d4e05ed7bba72919
F20101123_AABSKM pooput_c_Page_104.tif
72d8678a970ed78abee20576fd8a0741
62de3ca8e77cca0763c1f53de2d037cc86444a6d
F20101123_AABSJZ pooput_c_Page_084.tif
925efcb0cad890cc92f798d4467fe122
67ea10ce8a91a9d3ff9ee150f3aaa62a87012313
F20101123_AABSLB pooput_c_Page_123.tif
e7b0e28286e48f7fdaf7d44bc5bf2baf
f6693e84863fec0cf9c75d409f057b78be821aee
F20101123_AABSKN pooput_c_Page_106.tif
4ab357fc46ec0d970fa6e9db2f623300
b104bb3a7a4f78d5c52c89a9ee6771e990efc432
F20101123_AABSLC pooput_c_Page_124.tif
1e8b89ac8b78832b58069d2869dd0cc0
bc4c32bb7c517e49a69328933f98215a7449b380
F20101123_AABSKO pooput_c_Page_107.tif
61f8799dd7bea5e40f81459b6e67f6cc
9ff49110e23e9a51c20338d3fe6687f280fd892d
F20101123_AABSLD pooput_c_Page_125.tif
0feae783e543e8fa35643b3e3c08a709
48d333c1536ff1b22ff89141750bcbae23f7aea7
F20101123_AABSKP pooput_c_Page_109.tif
6d38cf3635ef310fc59f5bf8e3c81979
26662788f2cfe6b071f55a9ccb2d3bc837ff8d62
F20101123_AABSLE pooput_c_Page_126.tif
1f60fc1df403caa3f2398fd2a0982972
66600e89ea561fdd909a040357d30147997c068c
F20101123_AABSKQ pooput_c_Page_110.tif
9fd8976b9dd69c20a79fbac4ab4bd587
9adff2cc74d14114d22c04afa04c82edf30919ca
F20101123_AABSLF pooput_c_Page_131.tif
6a1cc4c7a4eef9d9fc9bfc7ca08eb773
84e68d11214e81afd8efc0dbbc720c5daa1f1a27
F20101123_AABSKR pooput_c_Page_111.tif
3f1664b5df240846af57ee8ea3f8a8f3
c2c2d00e3509a6243e8437ca428dee6098bb07d3
F20101123_AABSLG pooput_c_Page_132.tif
0f9f75b405a82161d55069d4e209c2c1
3af1d2766a06c57e9f3ed732b1f21ff2bf535dba
F20101123_AABSKS pooput_c_Page_112.tif
85dd81c3c49867d3ed17692a68c4889f
d6e21b78f23e5e676dfa20862c4dc07f6a260873
F20101123_AABSLH pooput_c_Page_133.tif
4221db30603ec647de9012c6e98f25be
5c7a96480e023dd334b14654999e2e179d0f70b5
F20101123_AABSKT pooput_c_Page_113.tif
0df437e93be8d3ee0d33e41bda6e00b4
683e6ced5406b9b193b9eb5d79a7be4a1ac7ab29
F20101123_AABSLI pooput_c_Page_134.tif
ce5b7668a82d92a7c6c28a4621f97552
fb6afa3f78674b13050a57d5651688782efda7a0
F20101123_AABSKU pooput_c_Page_114.tif
9f1b11c4620cf1ee125a010099520f92
8451298b85eb8987d4be1b775ed5619549298e31
F20101123_AABSLJ pooput_c_Page_135.tif
d426c0fe65c06acd278cbfb205d061fc
7038b42eed8b71801b8a43e644b9e6fb36812ad8
F20101123_AABSKV pooput_c_Page_115.tif
2541eb6c9f71e9797b88ccc625e4c913
de0f5f904ac4f65847d0844b7155aac4b2fa7935
F20101123_AABSLK pooput_c_Page_136.tif
f1340fc3e5fbd638bb19bb28d1b49409
40506843b52f68859ae1796892edf442736c6a06
F20101123_AABSKW pooput_c_Page_116.tif
44f73c40f11eae7fec9c95999b72b1ce
a03d22c5ea6ee6b2c3a30a791a1fd7035b40f38e
8423998 F20101123_AABSLL pooput_c_Page_137.tif
9ed7fcf34909eef821244850ebc960fd
196ee11614473011b2715731020b0398a4147b5f
F20101123_AABSKX pooput_c_Page_117.tif
e90a08ce15c5665317ef736e1b9599c3
38903757072d4d7e2533940baee1acce25ba9467
29646 F20101123_AABSMA pooput_c_Page_020.pro
84d50bc6414612efbeef8c8aea628ed0
7ef9a3c4db4acafbd7598c05b594f26054237420
F20101123_AABSLM pooput_c_Page_138.tif
4e602b93da838fbd86199e45675adbf5
7c3b782ed6b16f90579e992da47e231acc541eb1
F20101123_AABSKY pooput_c_Page_118.tif
dd628bba1e2945120082ac0c9656938c
00f596b16165a6bed2b5bba2b6b84708cb19f88a
42872 F20101123_AABSMB pooput_c_Page_022.pro
9befc2e39ea4363aa3de4efc9c933449
0d479a2ec8a9df1a114f9c72b2e3ab781ed6a9aa
F20101123_AABSLN pooput_c_Page_139.tif
e479c71cd8b2ffdd849fecaabb467e64
7068ab0550db907c4658dbdd2ec710e84dbe9b3a
F20101123_AABSKZ pooput_c_Page_119.tif
4dfe74662301fcd3916b952b7c1bc7de
8e67aaa835ef7aa3c8f73a06731a1f0c06312479
27996 F20101123_AABSMC pooput_c_Page_023.pro
ca2e5319bbd3b781b3b1584fa6537a22
69153692f3cdf9719767554dcf822169a406ed75
7721 F20101123_AABSLO pooput_c_Page_001.pro
ba93f8c581a7f9e8c79fe76685e61109
31b26a4b0bcf779d1961b649972b4ec735421918
33034 F20101123_AABSMD pooput_c_Page_024.pro
1400f25a940780878a87bfe49862992e
8bfb382651d909a55d723cc89db182305756bfee
2210 F20101123_AABSLP pooput_c_Page_002.pro
a11b4e5a8b4ccbceb54d2c6c39fa992c
1c5ec6f12955dbdbd88dde04cc8921b158aff1f3
45958 F20101123_AABSME pooput_c_Page_026.pro
1c8227219d46f390096c8c851b852710
0c807b042b83c6c75d083f7a5689c56000d015dc
40526 F20101123_AABSLQ pooput_c_Page_003.pro
3cb700ec6b90373e65ab0405356bf840
5fc87402bd7e110ac5cd34cc979dec82336acce6
15577 F20101123_AABSMF pooput_c_Page_028.pro
1c9f8f8b9efbb648a8bb8ffd87761416
3a039b76a9b291cce0c7a4cc1c69098db4757dba
88300 F20101123_AABSLR pooput_c_Page_005.pro
2dd90e440413e30943693de306605bad
1b525aa0858a40f94f6b2e0a24f8abdd30d975ea
23049 F20101123_AABSMG pooput_c_Page_029.pro
364f601a67f8649ea729297e59e7be6f
6ad8c3558e3fbb84a6f83291c99b58328582a7c8
57317 F20101123_AABSLS pooput_c_Page_008.pro
a552ad441bd8a5724655dfa8c4ab7e3d
a98c6225fc021940427ce2bf84ec0f76a319c62c
41550 F20101123_AABSMH pooput_c_Page_031.pro
69086d1c9280bc585e3234586b7f1620
0f19422df8798a11b23986c53ca4f7437e14ad4b
53270 F20101123_AABSLT pooput_c_Page_010.pro
e8781e520e12ae32b90184791a52c07d
0fc317b7dd89a99ee299c15bbe3510ff0c9ac8a8
34946 F20101123_AABSMI pooput_c_Page_032.pro
83fd0badab4318c5103902955e25a7a4
d49982bdeb517710c1a26fac8ec471c016b033e8
65515 F20101123_AABSLU pooput_c_Page_011.pro
54d9d37ecd9227fb77c4a9571a473bbf
7ecfd0584b878dfe7050be407e13becb5e3fbd22
33809 F20101123_AABSMJ pooput_c_Page_034.pro
690c04a57525d25ed1130a7d7d1eae66
6b84b329d768456df9a266ad0748e1a74ab5bdfa
27086 F20101123_AABSLV pooput_c_Page_012.pro
b33b8650cbfb733976e9a42c150213b5
473484641fc59307e1afa3c9d58f8985c16560ba
48162 F20101123_AABSMK pooput_c_Page_035.pro
a0aec8e08c79a7ac7f1b16ae17cb7a69
353aaed1ece3e071c9b03de5f033cca3b362e515
54344 F20101123_AABSLW pooput_c_Page_013.pro
d316cac4bbe7a8e88e79c82a6e0b230d
32078a2ec926c9cd3ca4914ef461aa1de065fb20
38222 F20101123_AABSML pooput_c_Page_036.pro
ca6a2ee57d59d38704fafa299bb83fcb
f206af263fb2314f46e565e0965666c4806def9b
17488 F20101123_AABSLX pooput_c_Page_017.pro
acb52c38510717aeafc41a3719dbe547
14bdc9616461052c569c8b67304ad6130424a5ec
32875 F20101123_AABSNA pooput_c_Page_059.pro
a0467d8f956a1b9ee57405daee289a82
00ac94b6a6ead6629cd097ca4bf2d62a9e7c1458
47687 F20101123_AABSMM pooput_c_Page_037.pro
d1684f2749a9cb2591988e1c39916309
c2103458263988112b0a06724e64f163cf28e582
18016 F20101123_AABSLY pooput_c_Page_018.pro
2ad06fee906d07159fb0d9db4c8698a5
3bddc38cb32ff66c1fed64b1b2c9163e2eb1862c
39279 F20101123_AABSMN pooput_c_Page_039.pro
9a81927eafdf27924d9bc1fa8496c89f
9f6a97d916edc98387d7cd27147c37841b6a578c
37657 F20101123_AABSLZ pooput_c_Page_019.pro
b40dcc21d43b51c330f14dbdca643477
061a172ce74d4367f597d5d6bb2c7fe42cd76a62
15187 F20101123_AABSNB pooput_c_Page_060.pro
d485babf630569081a1b497771d75708
ecbedcdb320616e10f4aa455d188cdbeaacbc25f
8098 F20101123_AABSMO pooput_c_Page_041.pro
c8cdb3b07082cfba55785e35af226bd3
78b9353404d45ab4da92a743feedbd7722a1a3a9
24314 F20101123_AABSNC pooput_c_Page_061.pro
c2c084e79f9478298ce8cde943c4f5d7
5be73211c86edc84bb3eb3a60a755a0351847808



PAGE 1

SYNTHESES AND STUDIES OF PERFLUOROALKYL SUBSTITUTED COMPOUNDS By CHAYA POOPUT A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLOR IDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 2005

PAGE 2

This dissertation is dedicated to my parents, Chatchawan and Payom Pooput.

PAGE 3

iii ACKNOWLEDGMENTS I express my deep gratitude to my advisor (Dr. William R. Dolbier, Jr.). Throughout the years I have spent in his labo ratory, I was able to acquire invaluable knowledge to help me achieve my goals. W ithout his ideas, guidance and support, I would not have been able to complete my research. I thank Dr. Samia At-Mohand for helping me get started in research in my first year. I thank Dr Dolbier’s group members for their help. I thank David Duncan for he lping me in experiments on TDAE analogue project. I thank the Chemistr y Department of the University of Florida for accepting me in the graduate program. I thank all my frie nds, especially Valerie, Igor, Rachel, Rafal, Janet, Jim, Gary, Rong and Hongfang for th eir support and friendship. I would like to thank again Valerie for always being here for me, for cheering me up when I was down and for sharing with me most of the wonderf ul moments I have in Gainesville. I also thank Valerie’s parents (Vale and Iris) for we lcoming me in their home in Puerto Rico and for giving me warmth and love that make me feel like I was a part of their family. I thank Valerie’s big family in Puerto Rico, S onia, Mia, Nilda, Nels on and Nydia for their love. I also thank my aunt Wanee for her suppo rt and love when I was in France. I thank my sister for being who she is and for her l ove. Finally I am eternally grateful to my parents. Because of their sacrifices, I was ab le to achieve this high level of education. Their constant support and love gave me strength.

PAGE 4

iv TABLE OF CONTENTS page ACKNOWLEDGMENTS.................................................................................................iii LIST OF TABLES...........................................................................................................viii LIST OF FIGURES.............................................................................................................x LIST OF SCHEMES........................................................................................................xiii ABSTRACT.....................................................................................................................xv i CHAPTER 1 INTRODUCTION...................................................................................................1 1.1 General Information.....................................................................................1 1.2 Previous Work.............................................................................................3 1.2.1 Starting Point...................................................................................3 1.2.2 Preliminary Results in the Group.....................................................4 1.2.3 New and Efficient Method for Synthesis of Trifluoromethyl Sulfides............................................................................................5 1.2.4 New and Efficient Method for Synthesis of Trifluoromethyl Selenides........................................................................................10 2 SYNTHESIS OF PERFLUOROALKYL THIO AND SELENOETHERS..........12 2.1 Introduction................................................................................................12 2.2 Synthesis of Pentafluoroethyl Thioethers..................................................14 2.3 Synthesis of Pentafluor oethyl Selenoethers...............................................16 2.4 Synthesis of Perfluorobutyl Thioethers.....................................................17 2.5 Synthesis of Perfluorobutyl Selenoethers..................................................19 2.6 Conclusion.................................................................................................19 2.7 Experimental..............................................................................................20 2.7.1 General Synthesis of Pentafluor oethyl Thio and Selenoethers : Synthesis of Phenyl Pentafluoroethyl Sulfide................................20 2.7.2 General Synthesis of Nonafluor obutyl Thio and Selenoethers : Synthesis of Phenyl Nonafluorobutyl Sulfide................................22

PAGE 5

v 3 PERFLUOROALKYLATION OF IMINE TOSYLATES....................................25 3.1 Introduction................................................................................................25 3.2 Synthesis of Tosyl Imines..........................................................................28 3.3 Pentafluoroethylation of Tosyl Imines.......................................................29 3.4 Perfluorobutylation of Tosyl Imines..........................................................31 3.5 Conclusion.................................................................................................33 3.6 Experimental..............................................................................................33 3.6.1 Syntheses of Tosyl Imines.............................................................33 3.6.2 General Procedure for Pentafluor oethylation of Tosyl Imines : Synthesis of MethylN -(3,3,3,2,2-pentafluoro-1-phenyl-propyl)benzenesulfonamide (3.1a)............................................................36 3.6.3 General Procedure for Perfluorobutylation of Tosyl Imines: Synthesis of 4-MethylN -[5,5,5,4,4,3,3,2,2-nonafluoro-(4methyl-phenyl)-propyl]-benzenesulfonamide (3.2b).....................40 4 PERFLUOROAKYLATION OF ALDEHYDES AND KETONES.....................44 4.1 Introduction................................................................................................44 4.2 Pentafluoroethylation of Aldehydes and Ketones......................................45 4.3 Perfluorobutylation of Aldehydes and Ketones.........................................47 4.4 Conclusion.................................................................................................48 4.5 Experimental..............................................................................................48 4.5.1 General Procedure of Pentafl uoroethylation of Aldehydes and Ketones: Synthesis of 1-Ph enyl-2,2,3,3,3-pentafluoropropan-1ol (4.2)............................................................................................48 4.5.2 General Procedure for Perfl uorobutylation of Aldehydes and Ketones: Synthesis of 1-Phenyl-2,2,3,3,4,4,5,5,5nonafluoropentan-1-ol....................................................................50 5 SYNTHESES AND STUDIES OF TETRAKIS(DIMETHYLAMINO)ETHYLENE ANALOGUES.........................52 5.1 Introduction................................................................................................52 5.2 Syntheses of TDAE Analogues.................................................................54 5.2.1 Synthesis of 1,3,1’,3’-Tetraalkyl-2,2’-bis(imidazolidene)............54 5.2.2 Synthesis of 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene).54 5.3 Attempts of Trifluoromethyla tion using the TDAE Analogues................56 5.3.1 Attempts of Trifluoromethyl ation using 1,3,1’,3’-Tetraalkyl2,2’-bis(imidazolidene) instead of TDAE......................................56 5.3.2 Nucleophilic Trifluoromethylati on of Phenyl disulfide using 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene).....................59 5.4 Conclusion.................................................................................................60 5.5 Experimental..............................................................................................60 5.5.1 Synthesis of 1,3,1’,3’-Tetraethyl-2,2’-bis(imidazolidene) (5.1)....60

PAGE 6

vi 5.5.4 Synthesis of 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene) (5.4)................................................................................................61 6 DIMERIC DERIVATIVES OF OCTAFLUORO[2,2]PARACYCLOPHANE (AF4) : A NEW SOURCE OF PERFLUOROALKYL RADICALS....................63 6.1 Introduction................................................................................................63 6.1.1 General Information.......................................................................63 6.1.2 Synthesis of AF4............................................................................64 6.2 Kinetic Studies of CF3-AF4-dimers...........................................................66 6.2.1 Synthesis of CF3-AF4-dimer..........................................................66 6.2.2 Thermal Decomposition of the CF3-AF4-dimer...........................68 6.2.3 Kinetic Study of Homolysis of CF3-AF4-Dimers..........................70 6.3 Kinetic Studies of C2F5-AF4-dimers.........................................................74 6.3.1 Synthesis of C2F5-AF4-dimers.......................................................74 6.3.2 Kinetic Studies of the Homolysis of C2F5-AF4-dimers.................76 6.4 Conclusion.................................................................................................80 6.5 Experimental..............................................................................................80 6.5.1 Synthesis of CF3-AF4-Dimer.........................................................80 6.5.2 Kinetic Studies of CF3-AF4-Dimer...............................................81 6.5.2.1 General procedure...........................................................81 6.5.2.2 Kinetic data and graphs for CF3-AF4-Dimer at 140.1 C.......................................................................82 6.5.2.3 Kinetic data and graphs for CF3-AF4-Dimer at 151.0 C...........................................................................84 6.5.2.4 Kinetic data and graphs for CF3-AF4-Dimer at 160.7 C...........................................................................86 6.5.2.5 Kinetic data and graphs for CF3-AF4-Dimer at 170.3 C...........................................................................88 6.5.2.6 Kinetic data and graphs for CF3-AF4-Dimer at 179.7 C...........................................................................90 6.5.3 Synthesis of C2F5-AF4-Dimer.......................................................92 6.5.4 X-ray Structure of C2F5-AF4-Dimers............................................93 6.5.5 Kinetic Studies of C2F5-AF4-Dimers.............................................96 6.5.5.1 General procedure...........................................................96 6.5.5.2 Kinetic data and graphs of C2F5-AF4-Dimers at 118.8 C...........................................................................97 6.5.5.3 Kinetic data and graphs of C2F5-AF4-Dimers at 125.7 C...........................................................................99 6.5.5.4 Kinetic data and graphs of C2F5-AF4-Dimers at 130.5 C.........................................................................101 6.5.5.5 Kinetic data and graphs of C2F5-AF4-Dimers at 139.6 C.........................................................................103 6.5.5.6 Kinetic data and graphs of C2F5-AF4-Dimers at 145.3 C.........................................................................105 6.5.5.7 Kinetic data and graphs of C2F5-AF4-Dimers at 151.3 C.........................................................................107

PAGE 7

vii 6.5.5.8 Kinetic data and graphs of C2F5-AF4-Dimers at 156.4 C.........................................................................109 6.5.5.9 Kinetic data and graphs of C2F5-AF4-Dimers at 161.0 C.........................................................................111 6.5.5.10 Kinetic data and graphs of C2F5-AF4-Dimers at 165.9 C.........................................................................113 GENERAL CONCLUSION............................................................................................115 LIST OF REFERENCES.................................................................................................116 BIOGRAPHICAL SKETCH...........................................................................................122

PAGE 8

viii LIST OF TABLES Table page 1-1 Trifluoromethylation of disulfides.............................................................................7 1-2 Trifluoromethylation of disulf ides using a higher amount of CF3I............................8 1-3 Synthesis of trifluoromethyl selenoethers................................................................11 2-1 Synthesis of pentaf luoroethyl thioethers..................................................................15 2-2 Synthesis of pentafl uoroethyl selenoethers..............................................................16 2-3 Synthesis of perfluorobutyl thioethers.....................................................................17 2-4 Synthesis of perfluorobutyl selenides......................................................................19 3-1 Synthesis of tosyl imines..........................................................................................28 3-2 Nucleophilic pentafluoroe thylation of tosyl imines.................................................30 3-3 Nucleophilic perfluorobutylation of tosyl imines....................................................32 4-1 Compared yields between pentafluor oethylation and trif luoromethylation of aldehydes and ketones..............................................................................................46 4-2 Perfluorobutylation of aldehydes and ketones.........................................................47 6-1 Rate constants of the 2 diasteromers of CF3-AF4-dimers........................................71 6-2 Half-life times of the homolysis of CF3-AF4-dimers..............................................72 6-3 Arrhenius plot data...................................................................................................74 6-4 Activation parameters for CF3-AF4-dimers.............................................................74 6-5 Rate constants of the 2 diasteromers of C2F5-AF4-dimers......................................77 6-6 Half-life times of the homolysis of C2F5-AF4-dimers.............................................77 6-7 Arrhenius plot data for C2F5-AF4-dimers................................................................78

PAGE 9

ix 6.8 Activation parameters for C2F5-AF4-dimers............................................................78 6-9 Kinetic data of d,l-CF3-AF4-Dimer at 140.1 C.......................................................82 6-10 Kinetic data of meso-CF3-AF4-Dimer at 140.1 C..................................................82 6-11 Kinetic data of CF3-AF4-Dimers at 151.0 C...........................................................84 6-12 Kinetic data of CF3-AF4-Dimers at 160.7 C...........................................................86 6-13 Kinetic data of CF3-AF4-Dimers at 170.3 C...........................................................88 6-14 Kinetic data of CF3-AF4-Dimers at 179.7 C...........................................................90 6-15 Crystal data and structure refinement.......................................................................95 6-16 Selected bond lengths [] and angles [].................................................................96 6-17 Kinetic data of C2F5-AF4-Dimers at 118.8 C.........................................................97 6-18 Kinetic data of C2F5-AF4-Dimers at 125.7 C.........................................................99 6-19 Kinetic graph of C2F5-AF4-Dimers at 130.5 C.....................................................101 6-20 Kinetic data of C2F5-AF4-Dimers at 139.6 C.......................................................103 6-21 Kinetic data of C2F5-AF4-Dimers at 145.3 C.......................................................105 6-22 Kinetic data of C2F5-AF4-Dimers at 151.3 C.......................................................107 6-23 Kinetic data of C2F5-AF4-Dimers at 156.4 C.......................................................109 6-24 Kinetic data of C2F5-AF4-Dimers at 161.0 C.......................................................111 6-25 Kinetic data of C2F5-AF4-Dimers at 165.9 C.......................................................113

PAGE 10

x LIST OF FIGURES Figure page 1-1 Prozac.................................................................................................................... ..1 1-2 Celebrex.................................................................................................................. 1 1-3 Fipronil.................................................................................................................. ..1 2-1 2A28: insecticide.......................................................................................................12 2-2 2B29: insecticide.......................................................................................................12 2-3 2C30: pesticide..........................................................................................................12 3-1 3A......................................................................................................................... ....25 3-2 3B......................................................................................................................... ....25 3-3 3C......................................................................................................................... ....27 3-4 3D......................................................................................................................... ....27 3-5 A resonance form of N -( Nmethyl-3-indolylmethylene)p methylbenzenesulfonamide......................................................................................31 4-1 4A56 : Fungicide.......................................................................................................44 4-2 4B57 : insecticide......................................................................................................44 5-1. Structure of a chiral TDAE analogue.........................................................................53 5-2 Non chiral TDAE analogue......................................................................................53 5-3 benzimidazole TDAE analogue...............................................................................54 5-4 Cyclic voltammogram for 1,3,1’,3’-Tet raethyl-2,2’-bis(imi dazolidene), C = 3mM in DMF + 0.1 mM Et4NBF4 at 20 C, scan rate: 0.2V/s.................................59 6-1 [2,2]-paracyclophane................................................................................................64

PAGE 11

xi 6-2 AF4........................................................................................................................ ...64 6-3 Trifluoromethyl-AF4 derivative...............................................................................65 6-4 19F NMR distinction examining the d,l and the meso forms of CF3-AF4-dimers...67 6-5 Arrhenius plot for the 2 diasteromers of CF3-AF4-dimers......................................73 6-6 19F NMR distinction examining the d,l and the meso forms of C2F5-AF4-dimers..75 6-7 Perspective view (ORTEP) of meso-C2F5-AF4-dimer.............................................76 6-8 Arrhenius plot for the 2 diasteromers of C2F5-AF4-dimers.....................................79 6-9 Kinetic Graph of d,l-CF3-AF4-Dimer at 140.1 C...................................................83 6-10 Kinetic Graph of meso-CF3-AF4-Dimer at 140.1 C...............................................83 6-11 Kinetic Graph of d,l-CF3-AF4-Dimer at 151.0 C...................................................85 6-12 Kinetic Graph of meso-CF3-AF4-Dimer at 151.0 C...............................................85 6-13 Kinetic Graph of d,l-CF3-AF4-Dimer at 160.7 C...................................................87 6-14 Kinetic Graph of meso-CF3-AF4-Dimer at 160.7 C...............................................87 6-15 Kinetic graph of d,l-CF3-AF4-Dimers at 170.3 C...................................................89 6-16 Kinetic graph of meso-CF3-AF4-Dimers at 170.3 C..............................................89 6-17 Kinetic graph of d,l-CF3-AF4-Dimers at 179.7 C...................................................91 6-18 Kinetic graph of meso-CF3-AF4-Dimers at 179.7 C..............................................91 6-19 X-ray structure of meso-C2F5-AF4-dimer................................................................94 6-20 Kinetic graph of d,l-C2F5-AF4-Dimers at 118.8 C.................................................98 6-21 Kinetic graph of meso-C2F5-AF4-Dimers at 118.8 C.............................................98 6-22 Kinetic graph of d,l-C2F5-AF4-Dimers at 125.7 C...............................................100 6-23 Kinetic graph of meso-C2F5-AF4-Dimers at 125.7 C...........................................100 6-24 Kinetic graph of d,l-C2F5-AF4-Dimers at 130.5 C...............................................102 6-25 Kinetic graph of meso-C2F5-AF4-Dimers at 130.5 C...........................................102 6-26 Kinetic graph of d,l-C2F5-AF4-Dimers at 139.6 C...............................................104

PAGE 12

xii 6-27 Kinetic graph of meso-C2F5-AF4-Dimers at 139.6 C...........................................104 6-28 Kinetic graph of d,l-C2F5-AF4-Dimers at 145.3 C...............................................106 6-29 Kinetic data of meso-C2F5-AF4-Dimers at 145.3 C.............................................106 6-30 Kinetic data of d,l-C2F5-AF4-Dimers at 151.3 C..................................................108 6-31 Kinetic data of meso-C2F5-AF4-Dimers at 151.3 C.............................................108 6-32 Kinetic graph of d,l-C2F5-AF4-Dimers at 156.4 C...............................................110 6-33 Kinetic graph of meso-C2F5-AF4-Dimers at 156.4 C...........................................110 6-34 Kinetic graph of d,l-C2F5-AF4-Dimers at 161.0 C...............................................112 6-35 Kinetic graph of meso-C2F5-AF4-Dimers at 161.0 C...........................................112 6-36 Kinetic graph of d,l-C2F5-AF4-Dimers at 165.9 C...............................................114 6-37 Kinetic graph of meso-C2F5-AF4-Dimers at 165.9 C...........................................114

PAGE 13

xiii LIST OF SCHEMES Scheme page 1-1 Trifluoromethylation of be nzaldehyde using fluoroform...........................................2 1-2 Trifluoromethylation of benzaldehyd e using trifluoromethyl zinc iodide.................2 1-3 Examples of trifluorom ethylation reactions using Me3SiCF3....................................3 1-4 Difluoromethylation reactions of aromatic aldehydes with TDAE...........................3 1-5 Difluoromethylation reactions of ethyl pyruvates with TDAE..................................4 1-6 Trifluoromethylation reacti on of aldehydes and ketones...........................................4 1-7 Trifluoromethylation re action of acyl chlorides.........................................................4 1-8 Trifluoromethylation reaction of vicinal diol cyclic sulfate.......................................5 1-9 Synthesis of trifluoromethyl phenyl sulfide via SRN1 type reaction..........................5 1-10 Synthesis of trifluoromethyl phenyl sulfide using various sources of CF3..............6 1-11 Synthesis of trifluoromethyl thioethers......................................................................6 1-12 Efficient synthesis of trifluoromethyl sulfides...........................................................7 1-13 Mechanism of trifluorom ethylation of disulfides.......................................................7 1-14 Another possible mechanism of form ation of trifluoromethyl sulfide.....................10 1-15 Synthesis of trifluoromethyl selenoethers................................................................10 2-1 Different methods for synthesis of pe rfluoroalkyl sulfides and selenides...............13 2-2 Synthesis of trifluoromethyl sulfides with CF3I / TDAE methodology...................13 2-3 Tandem CF3I process in the synthesis of trifluoromethyl sulfides..........................14 2-4 Pentafluoroethylation of disulfides..........................................................................15 2-5 Pentafluoroethyla tion of diselenides........................................................................16

PAGE 14

xiv 2-6 Synthesis of perfluorobutyl thioethers.....................................................................17 2-7 Synthesis of perfluorobutyl selenides......................................................................19 3-1 Trifluoromethylation of imin es using Ruppert’s reagent.........................................26 3-2 Trifluoromethylation of imines using CF3I / TDAE...............................................27 3-1 Synthesis of tosyl imines..........................................................................................28 3-2 Nucleophilic pentafluoroe thylation of tosyl imines.................................................29 3-3 Nucleophilic perfluorobutylation of tosyl imines....................................................31 4-1 Pentafluoroethylation of aldehydes and ketones......................................................45 4-2 Nucleophilic perfluorobutyla tion of aldehydes and ketones....................................47 5-1 CF3I / TDAE complex..............................................................................................52 5-2 Synthesis 1,3,1’,3’-tetraal kyl-2,2’-bis(imidazolidene)............................................54 5-3 Multi-step synthesis of benzimidazol TDAE analogue............................................55 5-4 Nucleophilic trifluoromethylation of benzaldehyde using 1,3,1’,3’-tetraalkyl2,2’-bis(imidazolidene)............................................................................................56 5-5 Synthesis of phenyl trifluoromethyl sulfide by using imidazolidene TDAE analogue...................................................................................................................57 5-6 Possible decomposition pathways for imidazolidene TDAE analogue....................57 5-7 Reactivities of imidazolidene carbene towards benzaldehyde................................58 5-8 Attempt of synthesis of phenyl trifluoromethyl sulfide by using 1,3,1',3'Tetramethyl-2,2'-bis(benzimidazolylidene).............................................................59 6-1 Synthesis of AF4......................................................................................................64 6-2 Mechanism of formation of AF4..............................................................................65 6-3 Synthesis of CF3-AF4-dimer....................................................................................66 6-4 Formation of CF3-AF4-dimer...................................................................................66 6-6 Two possible pathways for decomposition of CF3-AF4-dimer...............................68 6-7 Resulting products from radical trap ping in different possible mechanism pathway....................................................................................................................69

PAGE 15

xv 6-8 Kinetic study of homolysis of CF3-AF4-Dimers.....................................................70 6-9 Synthesis of C2F5-AF4-dimers.................................................................................75

PAGE 16

xvi Abstract of Dissertation Pres ented to the Graduate School of the University of Florida in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy SYNTHESES AND STUDIES OF PERFLUOROALKYL SUBSTITUTED COMPOUNDS By Chaya Pooput August 2005 Chair: William R. Dolbier, Jr. Major Department: Chemistry Numerous compounds containing perfl uoroalkyl groups are found to be biologically active and are largely used in pharmaceutical and agrochemical areas. Although several methods have been developed to incorporate trifluoromethyl group into molecules, few are for longer perfluoroalkyl chains. Nucleophilic trifluoromethylation has been largely developed in our laboratory by using CF3I and Tetrakis(dimethylamino)ethy lene (TDAE). This methodology was extended to longer perfluoroalk yl iodides. Pentafluoroethyl iodide and nonafluorobutyl iodide were used instead of trifluoromethyl iodide. Reactions with disulfides and diselenides provided efficiently perfluoroalkyl thioand selenoethers, where, in most cases, both ha lves of the disulfides or diselenides were converted quantitatively to thio or selenoethers. Numerous pentafluoroethyl and nonafl uorobutyl substituted amines could be obtained in high yields by extending the methodology with tosyl imines.

PAGE 17

xvii Reactions with aldehydes and ketones provi ded good yields of pentafluoroethyl substituted alcohols. But reactions using nonafluorobutyl iodide a fforded low yields. The extension of CF3I / TDAE methodology to longer pe rfluoroalkyl iodides will allow us to access to a much larger number of biologica lly active compounds. Several TDAE analogues were also synt hesized but their reactivity towards CF3I is completely different from TDAE and c ouldn’t be used as TDAE substituents. The syntheses and kinetic studies of pe rfluoroalkyl subst ituted AF4 dimers provided valuable information on the use of these compounds as a stable source of perfluoroalkyl radicals.

PAGE 18

1 CHAPTER 1 INTRODUCTION 1.1 General Information Pharmaceutical and agrochemical industrie s have a growing interest in compounds containing perfluoroalkyl groups. Many ne w drugs contain trifluoromethyl groups: examples are shown in Figures 1-1 and 1-2: O F3C NHCH3 N S N CF3O O H2N Figure1-1. Pro zac Figure1-2. Celebrex N N CF3S NC Cl Cl NH2O CF3 Figure1-3. Fipronil Among the several methods of incorporat ing the trifluoromethyl group into a compound, one of the most useful is to generate in situ the unstable trifluoromethyl anion to undergo nucleophilic trifluoromethyl ation on electrophilic substrates.

PAGE 19

2 Various methods have been used to gene rate the trifluoromethyl anion: i) The groups of Roques1 and Normant2 effectively performed nucle ophilic trifluoromethylation by using fluoroform (CF3H) in the presence of base; and ii) Kitazume3 used trifluoromethylzinc iodide, pr epared from trifluoromethyl iodide and zinc powder with ultrasonic irradiation, as a trifluoromethylation reagent (Scheme 1-2). H O CF3H+1) DMF, -50 oC 2) tBuOK, 1h 3) AcOH, 0 oC 20 oC H OH CF3Yield=67% Scheme 1-1. Trifluoromethylation of ben zaldehyde using fluoroform Curently the most commonly used source of the nucleophilic trifluoromethyl anion is (trifluoromethyl)trimethylsilane (TMSCF3). In the past few years the groups of Prakash and Shreeve have developed the method of generating in situ CF3 by reaction of (trifluoromethyl)trimethylsilane (CF3TMS) with TBAF,4 CsF.5 Fuchikami6 reported that trifluoromethylation reactions of carbonyl compounds can also be catalyzed by Lewis bases, such as triethylamine, pyridine or triphenyl phosphine. H OultrasoundH OH CF3Yield = 72% CF3IZn ++ DMF Scheme 1-2. Trifluoromethylation of benzal dehyde using trifluoromethyl zinc iodide Extensive research had been performed on the use of this reagent with different substrates, such as ketones, esters and disulfides.

PAGE 20

3 R1R2O Me3SiCF3R1R2OH CF3CsF H3O++ R1OMe O Me3SiCF3Bu4N+ F-H3O++ R1CF3O R-S-S-R Me3SiCF3THF 0oC ++ R-S-CF3Bu4N+ FScheme 1-3. Examples of trif luoromethylation reactions using Me3SiCF3 5, 7, 8 Even though (trifluoromethyl )trimethylsilane is a pow erful trifluoromethylation agent, it is very expensive. Our group want ed to find a less expensive and more direct way to generate the nucleophilic CF3 anion. 1.2 Previous Work 1.2.1 Starting Point Since 1998, with the colla boration of Dr. Maurice Mdebielle, we have demonstrated that tetrakis(dimethylamino)et hylene (TDAE) can be used as an efficient reductant to generate nucleophilic difl uoromethyl anions from chloroand bromodifluoromethyl compounds.9, 10 RCF2X ArCHO DMF OH Ar CF2R H -200to R T TDAE Scheme 1-4. Difluoromet hylation reactions of arom atic aldehydes with TDAE RCF2XCH3COCO2Et DMF OH H3C CF2R CO2Et -200to R T TDAE

PAGE 21

4 Scheme 1-5. Difluoromet hylation reactions of et hyl pyruvates with TDAE Pawelke earlier demonstrated that TDAE coul d be used with trifluoromethyl iodide to prepare CF3TMS from TMSCl.11 With these results, we decided to use TDAE to reduce trifluoromethyl iodide into trifluoromethyl anion. 1.2.2 Preliminary Results in the Group With the aldehydes and ketones, the CF3I / TDAE system provided very good yields, which were comparable to thos e obtained in analogous reactions using CF3TMS.12 R1R2O CF3I DMF OH R1CF3R2TDAE -20 0 to RT h 12 hrs 1 eq2.2 eq2.2 eq Scheme 1-6. Trifluoromethylati on reaction of aldehydes and ketones Aryl acyl chlorides also underwent clean recations.13 Cl O X O O F3C CF3XX CF3I / TDAE DME -20O C to RT RT, 2 hrs Scheme 1-7. Trifluoromethyla tion reaction of acyl chlorides Unfortunately the CF3I / TDAE system was not su ccessful in reactions with epoxides. But in 1988 Gao and Sharpless demonstr ated that vicinal di ol cyclic sulfates could be used as epoxide equiva lents, with a hi gher reactivity.14 O S O O O CF3I THF CF3HO I HO OH F3C TDAE -20o C to RT 20% H2SO455% < 1% 40%5 hrs+ 1 eq 2.2 eq 2.2 eq 53-95 % 48-98 %

PAGE 22

5 Scheme 1-8. Trifluorom ethylation reaction of vici nal diol cyclic sulfate The reaction is highly regios elective because only 1% of the other isomer is formed. Since the cyclic sulfate is highly reactive, competition between the iodide anion and the trifluoromethyl anion occurred, wh ich did not happen with other substrates.15 1.2.3 New and Efficient Method for Synt hesis of Trifluoromethyl Sulfides Aryl trifluoromethyl sulfides continue to attract much interest within pharmaceutical companies, as witnessed by the significant number of process patent applications recently submitted that are devoted to their preparation17. This interest derives from the recogni zed potential of the SCF3 group to have a positive influence on biological activity. Diverse methods have been reported for the synthesis of aryl trifluoromethyl sulfides18, but two seem to emerge as preferred methods. The first is the SRN1 reaction of aryl thiolates wi th trifluoromethyl iodide or bromide. Yagulpolskii was the first to repor t the reaction in 1977, using trifluoromethyl iodide and UV irradiation19: Ph-SHCF3I CH3CN, 0 5 oC + Ph-S-CF3NaOCH3,UV 89% Scheme 1-9. Synthesis of trif luoromethyl phenyl sulfide via SRN1 type reaction Wakselman and Tordeux used trifluor omethyl bromide in high pressure (2 atm),20, 21 and with other variations,22, 23 this method is generally efficient when using aryl thiolates but gives a much lowe r yield when using alkanethiolates.24 The other popular method involves the reacti on of trifluoromethyl anion (generated in situ by various methods) with aryl and alkyl disulfides:

PAGE 23

6 PhS-SPhCF3SiMe3THF, 0 oC +Ph-S-CF332% 8Ph-S -+ Bu4N+ FPhS-SPhCF3CO2K +Ph-S-CF3sulfolane, 56% 2584% 26Ph-S -+ PhS-SPh + Ph-S-CF387% 27Ph-S -+tBuOK NN OH F3C H Ph Scheme 1-10. Synthesis of trifluoromethyl phenyl sulfide using various sources of CF3 Although good yields can be obtained, the method suffers from the fact that half of the disulfide is wasted in the process (formation of thiolates for the other half). In our investigation16, the CF3I / TDAE system turned out to be a better method for synthesis of trifluoromethyl sulfides than w ith Ruppert reagents (Table 1-1). Both aryl and aliphatic disulfides provided near 100 % yield. The reaction is very fast only 2 hours of stirring at room temperature was suffi cient to give a quantit ative yield, as shown in the entries 4 and 5. R-S-S-RTDAECF3I DMF 0 oC to RT R-S-CF3+ + RT several hr 1 eq.2.2 eq2.2 eq Scheme 1-11. Synthesis of trifluoromethyl thioethers

PAGE 24

7 Table 1-1. Trifluoromet hylation of disulfides entry R Stirring time at RT (hrs) NMR yield 1 Phenyl 12 80 2 butyl 12 >98 3 ethyl 12 >98 4 butyl 4 >98 5 butyl 2 >98 R-S-S-RTDAECF3I DMF 0 oC to RT R-S-CF3+ + RT several hr 1 eq.2.2 eq4.2 eq 180 200%based of equivalents of disulfides Scheme 1-12. Efficient synthesi s of trifluoromethyl sulfides It has been demonstrated that the mechan ism of the reaction is as shown in the Scheme 1-13. TDAECF3I CF3R-S-S-R R-S CF3I CF3R-S-CF3R-S-CF3I I R-S + TDAE 2++ ++ + + Scheme 1-13. Mechanism of trif luoromethylation of disulfides It occurred to us that CF3I could also be used as a substrate for reaction, via the SRN1 mechanism, with the thiola te coproduct; thus, potentially enabling both halves of the disulfide to be used in a one pot reaction, where CF3I would be used in two different reactions, both of which l ead to the same desired product. First TDAE reduces CF3I to nucleophilic “CF3”, which reacts with the disulfide to form trifluoromethyl sulfide and

PAGE 25

8 thiolate. The resulting thiolate reacts with the excess of CF3I, in a SRN1 type mechanism to create the second molecule of sulfide. When more than 4.2 equivalents of CF3I are used while the quantity of TDAE stays at 2.2 equivalents, trifluoromethyl sulfides can be obtained at nearly 200% yield, based on the number of equivalents of disulfides, as shown in the Table 1-2. Table 1-2. Trifluoromethyl ation of disulfides us ing a higher amount of CF3I entry R Equiv. of CF3I Stirring time at RT (hrs) NMR yield* 1 Phenyl 5 12 186 2 butyl 5 12 170 3 4-pyridyl 5 12 200 4 butyl 5 4 170 5 butyl 4.2 4 175 6 butyl 3.2 4 130 7 butyl 4.2 2 170 8 ethyl 4.2 2 180 9 2-pyridyl 4.2 2 180 10 t-butyl 4.2 12 0 11 2-nitrophenyl 4.2 2 185 12 benzothiazolyl4.2 2 190 13 4-aminophenyl4.2 12 20 S N benzothiazolyl group *based of number of equivalents of disulfides The entries 1 to 3 show that with 5 equivalents of CF3I, yields of nearly 200% could be obtained whether with aryl disulfide or alkyl disulfide. Th e following entries are attempts to optimize the pro cedure: 3.2 equivalents of CF3I did not seem to be sufficient,

PAGE 26

9 since the yield was only 130% (e ntry 6) whereas more than 4.2 equivalents gave nearly quantitative yields. Moreover 2 hours of stir ring at room temperature was sufficient. Although with t-butyl disulfide, we were unable to perform the trifluoromethylation (entry 10), the result is nevertheless interesting because this shows a high influence of the steric effect for the reaction. Moreover the lack of reactivity of t-butyl disulfide has been noted previously, when CF3TMS was used as trifluoromethyl anion source.8 The entry 13 revealed another limitation of this methodology: CF3 anion being extremely unstable reacts preferable first towards acidic protons such as the ones present in the amino group hence the very low yield for the reaction w ith 4-aminophenyl disulfide (Table 1-2, entry 13). All the groups containing acidic protons need then to be protected first before undergoing trifluoromethylation with CF3I / TDAE method. In the case of 4-aminophenyl disulfide, 4-nitrophenyl disulfide can be used and the nitro group can be reduced later to obtain the amino group; the amino group can also be protected twice with BOC to avoid the harsh conditions of reduction of nitro group. It might be argued that these results could derive from reduction by TDAE of disulfide to 2 equivalents of thiolate anion. The thiolate could react then with CF3I proceeding entirely via SRN1 type reaction. If that were the case, the 2.2 equivalents of CF3I along with 2.2 equivalents of TDAE should have been sufficient to obtain the high yields observed in the Table 1-2. However, in the case where 2.2 equivalents of CF3I were used (Table 1-1), yields never ex ceeded 100%. This probably means that CF3I is reduced faster than the disulfides.

PAGE 27

10 TDAE R-S-S-R 2 R-S 2 CF3I 2 R-S 2 R-S-CF32 I +TDAE 2+ ++ Scheme 1-14. Another possible mechanism of formation of trif luoromethyl sulfide Nevertheless, a control reaction was carried out to provide more definitive evidence for the proposed dual mechanism synthetic process. CF3I (5 equiv.) and TDAE (2 equiv.) were added first together at –20C so th at TDAE would be totally oxidized by the reaction with CF3I. The solution was then allowed to warm to -5C, at which time, nbutyl disulfide was introduced. At this point there should be little if any TDAE remaining to react with the disu lfide. Despite this, th e observed yield from this reaction was 160%, which compares well with the 170% obtained when using the norma l procedure (Table 12, entry 5). This can be concluded that th e reaction likely proceeds via the two-stage process described earlier. Thes e interesting results mean that the disulfides provide two molecules of trifluoromethyl sulfides, whic h was never observed before in the other methods. 1.2.4 New and Efficient Method for Synthe sis of Trifluoromethyl Selenides Since diselenides have similar reactivities than that of disulfides, reactions of nucleophilic trifluoromethylation were al so performed on diphenyl diselenide16. R-Se-Se-RTDAECF3I DMF 0 oC to RT R-Se-CF3RT overnight 1 eq.2.2 eq + + 4.2 ~200%based of number of equivalents of diselenides Scheme 1-15. Synthesis of trifluoromethyl selenoethers

PAGE 28

11 Table1-3. Synthesis of tr ifluoromethyl selenoethers Entry R NMR Yield (%)* 1 phenyl 198 2 4-Chlorophenyl 200 3 methyl 180 *based of number of equivalents of diselenides The methodology is efficient for both aliphatic and aromatic diselenides. The CF3I / TDAE methodology are very effici ent for many electr ophilic subtrates, we are interested now to extend this methodology to longe r perfluorinated chains by using other perfluoroa lkyl iodides. We would be able to access to a higher amount biologically active compounds.

PAGE 29

12 CHAPTER 2 SYNTHESIS OF PERFLUOROALKYL THIO AND SELENOETHERS 2.1 Introduction Parallel to trifluorothioethers, trifluoroselenoethers, longer perfluoroalkyl chains are also developed to be used as biologically activ e compounds. Few examples are given below. ClCF3Cl N S H3C SCF2CF3 NH2H N Br BrSCF2CF3O Figure 2-1. 2A28: insecticide Figure 2-2. 2B29: insecticide Cl CF3Cl N N CN SC4F9N H N Figure 2-3. 2C30: pesticide Despite the increasing interest in perfluor oalkyl sulfides, few methods have been developed to synthesize them. The two ma in methods consists in first through SRN1 reaction of aryl thiolates with perfloroalkyl iodide31 or bromide.32 The second method involves perfluoroalkyl ani on, generated from thermal decarboxylation of potassium

PAGE 30

13 perfluoroalkyl carboxylate,33 with aryl disulfides with the inconvenience of possible carbanion rearrangement or decomposition and one half of the disulfide is wasted. Another notable method for synthesis of perf luoroalkyl selenides consists in reaction between perfluoroalkyl ra dicals and diselenides.34 So far there is no efficient method for synthesis of perfluoroalk yl aliphatic sulfides. PhS-SPh + CF3CF2CO2K PhS-CF2CF3 + PhSK 70 %33PhSe-SePh + 2 C4F9I HOCH2SO2Na 2 PhSe-C4F957%34PhSH + C4F9I NaH PhS-C4F966% 31PhSK + CF3CF2BrPhS-CF2CF333% 32 Scheme 2-1. Different methods for synthesis of perfluoroa lkyl sulfides and selenides Our laboratories have developed a new and efficient method for synthesis of trifluoromethyl sulfides and selenides, using CF3I / TDAE system.16 This methodology has now been extended to l onger perfluoroalkyl iodides. R-S-S-RTDAECF3I DMF 0 oC to RT R-S-CF3+ + RT several hr 1 eq.2.2 eq4.2 eq 180 200%based of equivalents of disulfides Scheme 2-2. Synthesis of tr ifluoromethyl sulfides with CF3I / TDAE methodology

PAGE 31

142.2 Synthesis of Pentafluoroethyl Thioethers The same way that TDAE reduces trifl uoromethyl iodide in to trifluoromethyl anion, pentafluoroethyl iodi de was also expected to be reduced by TDAE into pentafluoroethyl anion. The tandem pro cess, involving nucleophilic attack of trifluoromethyl anion to disulfide followed by SRN1 by the resulting thiolate on the excess of CF3I (Scheme 2-3), was also expected. TDAECF3I CF3R-S-S-R R-S CF3I CF3R-S-CF3R-S-CF3I I R-S + TDAE 2++ ++ + + Scheme 2-3. Tandem CF3I process in the synthesis of trifluoromethyl sulfides16 The first experiment was carried out usi ng 1 equivalent of phenyl disulfide, 4.2 equivalents of C2F5I and 2.2 equivalents of TDAE added at -20 C. The color of the solution turned quickly deep red as TDAE was introduced. This may show the formation of the complex between TDAE and C2F5I, like in the case between TDAE and CF3I. The reaction mixture was allowed to warm up slowly. But unlike CF3I where the complex with TDAE starts decomposing at 0 C, the complex with C2F5I started decomposing around -10 C, as white salt could be seen forming. Apparently the complex between C2F5I and TDAE is less stable than that with CF3I. But the fact that TDAE was able to form a complex with C2F5I was a good sign meaning that the reaction may proceed in the same way as with CF3I / TDAE. The mixture was stirred overnight. 19F NMR was taken to calculate the yield. The reaction yielded 198 % based on the number of equivalents of disulfides (Table 2-1, entry 1).

PAGE 32

15 R-S-S-RTDAECF3CF2I DMF -10 oC to RT R-S-CF2CF3++ RT several hr 1 eq.2.2 eq4.2 eq Scheme 2-4. Pentafluoroe thylation of disulfides Reactions with different disulfides (aro matic and aliphatic) were then performed. The results are shown in Table 2-1. Table 2-1. Synthesis of pe ntafluoroethyl thioethers Entry R time at RT (hrs) NMR yield* 1 Phenyl32 12 >198 2 phenyl 2 >198 3 ethyl 2 135 4 ethyl 4 170 5 ethyl 12 175 6 butyl 12 180 7 2-pyridyl35 2 >198 8 4-pyridyl 2 190 *Based on the number of equivalents of disulfides The entries 2, 7 and 8 proved th at, as in the case of CF3I, 2 hours are sufficient to obtain quantitative yield for aryl disulfides. But in entries 3 to 5, two, even four hours didn’t seem to be sufficient to obtain good yields in the case of aliphatic disulfides. The mixture required to stirring overnight to be able to obtain 175 %. Even though, the yields are very similar to the ones with CF3I, aliphatic disulfides require a much longer time. This may be explained by the fact that it is more diificult for aliphatic thiolates to undergo SRN1 reaction. Somehow the presence of TDAE seems to enhance the reactivity

PAGE 33

16 of aliphatic thiolates on SRN1 reaction, since we could alwa ys obtain good yields from aliphatic disulfides with CF3I / TDAE system. In the case of C2F5I the complex formed with TDAE is less stable than with CF3I and this may one of th e reasons why the reaction is slower for aliphatic disulfides. It may also come from the fact that C2F5I is less reactive as a substrate in the SRN1 process. In spite of longer re action time for aliphatic disulf ides, the yields obtained are similar to the ones from CF3I. The two halves of the disulfides are used efficiently to form two molecules of pe ntafluorethyl thioethers. 2.3 Synthesis of Pentafluoroethyl Selenoethers Since diselenides have similar reactiv ities as disulfides. The reactions of nucleophilic pentafluoroethylation were also performed on diselenides. R-Se-Se-RTDAECF3CF2I DMF -10 oC to RT R-Se-CF2CF3RT overnight 1 eq.2.2 eq + + Scheme 2-5. Pentafluoroe thylation of diselenides Table 2-2. Synthesis of pe ntafluoroethyl selenoethers Entry R Eq. of C2F5I NMR yield* (%) 1 Phenyl34 2.2 100 2 phenyl 4.2 200 3 4-chlorophenyl 4.2 200 *Based on the number of equivalents of diselenides As expected, from 1 equivalent of diselenides, 2.2 equivalents of C2F5I gave quantitatively 1 equivalent of pentafluoroeth yl selenides (Table 22, entry 1) and 4.2 equivalents provided efficiently 2 equivalents of selenides.

PAGE 34

17 2.4 Synthesis of Perfluorobutyl Thioethers Since the nucleophilic perfluoroalkylati on using TDAE was successfully extended to C2F5I, longer perfluoroalkyl i odides were then considered for experiments, we decided to performed reactions w ith nonafluorobutyl iodided R-S-S-RTDAEC4F9I DMF -20 oC to RT R-S-C4F9+ + RT overnight 1 eq.2.2 eq Scheme 2-6. Synthesis of perfluorobutyl thioethers The reactions were performed in the sa me fashion as the usual reactions of trifluoromethylation of disulfides, with the difference that C4F9I is a liquid instead of a gas like CF3I or C2F5I, the total reflux condenser was not needed any longer. The complex C4F9I / TDAE seems to be much less unstable than the ones from CF3I / TDAE, since the usual TDAE salt was formed just abov e -20 C, very shortly after the addition of TDAE. Table 2-3. Synthesis of perfluorobutyl thioethers Entry R Eq. of C4F9I NMR yield* (%) 1 Phenyl36 2.2 70 2 ethyl 2.2 40 3 butyl 2.2 40 4 2-pyridyl37 2.2 100 5 4-pyridyl 2.2 200 6 phenyl 4.4 140 7 butyl 4.4 40 8 2-pyridyl 4.4 195 *Based on the number of equivalents of disulfides

PAGE 35

18 Aryl disulfides gave satisfactory to good yi elds (Table 2-3, entries 1 and 4) when 2.2 equivalents of C4F9I were used. But aliphatic disulfides resulted in only modest yields, 40%, (Table 2-3, entries 2 and 3). Th is may be explained by the low stability of the C4F9I / TDAE complex or th e low reactivity of C4F9 anion towards aliphatic disulfides. The case of 4-pyridyl disulfide (Table 2-3, entry 5) proved to be very interesting. With only 2.2 equivalents of C4F9I, we were able to obtain 2 equivalents of perfluorobutyl 4-pyridyl sulfide, where usually 4.2 equivalent s were needed to obtain the same results in other cases. This means that the tandem process16 (where the perfluoroalkyl anion, formed by reduction of perfluoroalkyl iodide by TDAE, attacks disulfide to form the first thioether and then the resulting thiolate reacts with the excess of perfluoroalkyl iodide through SRN1 reaction to form the second thioether (Scheme 23)) is not applicable anymore in this case. TDAE didn’t reduce C4F9I into C4F9anion but instead reduced entirely 4-pyrid yl disulfide, forming 2 equivalents of thiolate which react with C4F9I through SRN1 mechanism. It seems that C4F9I is not as reactive towards TDAE as CF3I or C2F5I and since the disulfide was also pr esent in the reaction mixture when TDAE was added and aryl disu lfides can be easily reduced, TDAE preferably reduced 4pyridyl disulfide over C4F9I. This problem was not encountered in the case of CF3I and C2F5I because their reactivity towards TDAE was high enough that TDAE reduced them first. When 4.4 equivalents of C4F9I were used on phenyl or 2-pyridyl disulfide, 140 % and 195 % of thioethers were obtained respectiv ely (Table 2-3, entries 6 and 8). But 40 % yield was only obtained for butyl disulfide, the same yield as when 2.2 equivalents of

PAGE 36

19 C4F9I were used. It seems that aliphatic thio lates anions couldn’t undergo reaction at all through an SRN1 reaction with C4F9I. 2.5 Synthesis of Perfluorobutyl Selenoethers The syntheses of perfluorobutyl se lenides were also performed. R-S-S-RTDAEC4F9I DMF -20 oC to RT R-S-C4F9+ + RT overnight 1 eq.2.2 eq Scheme 2-7. Synthesis of perfluorobutyl selenides Table 2-4. Synthesis of perfluorobutyl selenides Entry R Eq. of C4F9I NMR yield* (%) 1 Phenyl34 2.2 200 2 methyl 2.2 200 *Based on the number of equivalents of diselenides As with 4-pyridyl disulfide, both aryl and aliphatic diselenides only underwent through SRN1 process, resulting in nearly 200 % yields when 2.2 equivalents of C4F9I were used (Table 2-4). Cont rary to disulfides, alipha tic deselenides could react quatitatively with C4F9I via SRN1 process. 2.6 Conclusion The nucleophilic perfluoroalkylat ion methodology developed with CF3I / TDAE system was successfully extended to C2F5I: similar results were obtained and the two halves of disulfides and deselenides were efficiently used. The methodology seemed to reach its limits with C4F9I. Whereas some aryl disulfides still gave good yields, aliphatic disulfides resulted in poor yields. But the most important point is the fact that for some disulfides and for all th e diselenides, TDAE was unable to react with C4F9I and

PAGE 37

20 preferably reduced disulfides or diselenide s instead, forcing the reactions to undergo exclusively through SRN1 mechanism of thiolate anion. From a synthetic point of view, this didn’t present a problem. On the contrary, a smaller amount of TDAE and perfluorobutyl iodide was used to give 200% yi elds. But in the mechanistic point of view, the tandem process, where the perfluoroalkyl iodide switches roles from being a reactant to being a substrate in one pot reaction, couldn’t be appl ied anymore and the role of TDAE was only to reduce the disulfides. Moreover reducing disulfides to form thiolates seems to be much less convenient than deprot onating a more easily available thiols by a base, as the usual methods for perf luoralkyl thioether synthesis via SRN1 reactions. However this C4F9I / TDAE, even when TDAE se rved only as reductant of disulfides, still presents an advantage to ot her methods where the yields were not higher than 60 %31,34 2.7 Experimental Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus 300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with external tetramethylsilane (TMS, = 0.00 ppm) as a reference. Fluorine (19F) and proton (1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFCl3, = 0.00 ppm) as a reference for 19F NMR and TMS ( = 0.00 ppm) for 1H NMR. Deuterated chloroform (CDCl3) was used as NMR solvent. 2.7.1 General Synthesis of Pentafluoroethyl Thio and Selenoethers : Synthesis of Phenyl Pentafluoroethyl Sulfide In 25 mL, 3-neck-round bottom flask, equi pped with a dewar type condenser and N2, diphenyl disulfide (0.8 g, 3.68 mmol) was disolved in 10 mL of anhydrous DMF. The solution was cooled at -20 C. Pentafluoroe thyl iodide (3.8 g, 15.45 mmol) was then

PAGE 38

21 introduced to the solution. TDAE (2 mL, 8.1 mmol) was added around -15 C. The reaction mixture became quickly dark red. The reaction was allowed to warm up slowly to room temperature. And as the bath temper ature reached -10 C white solid was formed. The reaction mixture was stirred at room temp erature for 2 hours (or overnight in the case of alkyl disulfides). The orange solution was filtered and the solid was washed with diethyl ether. The orange solution was filtered and the solid was washed with diethyl ether (20 mL). 20 mL of water was added to the ether solution. The two phases were separated and the aqueous phase was extracte d with 20 mL of ether 2 more times. The combined ether layers were wash ed with brine and dried over MgSO4. The solvent was removed and the crude product was purif ied by silica gel chromatography (CH2Cl2 / hexanes = 1:9) to give phenyl pentafl uoroethyl sulfide in the yield of 198% 19F NMR(300 MHz, CDCl3) -83.00 (t, JFF = 3.1 Hz 3F, CF3); -92.32 (q, JFF = 3.1 Hz ,2F, CF2) ppm Ethyl Pentafluoroethyl Sulfide 1H NMR(300 MHz, CDCl3) 2.70 (q, J = 7.2 Hz, 2H, CH2); 1.32 (t, J = 7.2 Hz, 3H, CH3) 19F NMR(300 MHz, CDCl3) -83.00 (t, JFF = 3.2 Hz ,3F, CF3); -92.32 (q, JFF = 3.2 Hz, 2F, CF2) ppm Butyl Pentafluoroethyl Sulfide 1H NMR(300 MHz, CDCl3) 2.69 (t, J = 7.3 Hz, 2H, CH2); 1.66 (quintet, J = 7.6 Hz, 2H, CH2); 1.42 (sextuplet, J = 7.6 Hz, 2H, CH2); 0.93 (t, J = 7.3 Hz, 3H, CH3) 19F NMR(300 MHz, CDCl3) -82.95 (t, JFF = 3.2 Hz ,3F, CF3); -92.55 (q, JFF = 3.2 Hz, 2F, CF2) ppm

PAGE 39

22 2-Pyridyl Pentafluoroethyl Sulfide35 1H NMR(300 MHz, CDCl3) 8.47 (m, 1H, ArH); 7.62 (m, 2H, ArH); 7.11 (m, 1H, ArH) 19F NMR(300 MHz, CDCl3) -83.17 (t, JFF = 2.01 Hz ,3F, CF3); -91.03 (q, JFF = 2.01 Hz ,2F, CF2) ppm 4-Pyridyl Pentafluoroethyl Sulfide 1H NMR(300 MHz, CDCl3) 8.51 (dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 2H, ArH); 7.37 (dd, J1 = 4.7 Hz, J2 = 1.75 Hz, 2H, ArH) 19F NMR(300 MHz, CDCl3) -82.95 (t, JFF = 2.14 Hz 3F, CF3); -90.78 (q, JFF = 2.14 Hz, 2F, CF2) ppm Phenyl Pentafluoroethyl Selenide34 19F NMR(300 MHz, CDCl3) -84.74 (t, JFF = 3.2 Hz, 3F); -92.14 (q, JFF = 3.2 Hz, 2F, CF2) ppm 2.7.2 General Synthesis of Nonafluorobutyl Th io and Selenoethers : Synthesis of Phenyl Nonafluorobutyl Sulfide In a 25 mL round bottom flask, equipped with a rubber septum and N2, diphenyl disulfide (0.8 g, 3.68 mmol) was disolved in 10 mL of anhydrous DMF. The solution was cooled at -30 C. Nonafluorobut yl iodide (1.4 mL, 15.45 mmol) was then introduced to the solution. TDAE (2 mL, 8.1 mmol) wa s added around -20 C. The reaction mixture became quickly dark red. White solid was fo rmed shortly after the addition of TDAE. The mixture was allowed to warm up slowly to the room temperature was stirred overnight. The orange solution was filtered a nd the solid was washed with diethyl ether (20 mL). 20 mL of water was added to the et her solution. The two phases were separated and the aqueous phase was extracted with 20 mL of ether 2 more times. The combined

PAGE 40

23 ether layers were washed w ith brine and dried over MgSO4. The solvent was removed under vacum and the crude product was pur ified by silica gel chromatography (CH2Cl2 / hexanes = 1:9) to give phenyl nonafluo robutyl sulfide in the yield of 140% 19F NMR(300 MHz, CDCl3) -81.28 (t, JFF = 10.2 Hz 3F, CF3); -87.43 (m, 2F, SCF2); -120.46 (m, 2F, CF2); -125.90 (m, 2F, CF2) ppm Ethyl Nonafluorobutyl Sulfide 1H NMR(300 MHz, CDCl3) 2.70 (q, J = 7.2 Hz, 2H, CH2); 1.32 (t, J = 7.2 Hz, 3H, CH3) 19F NMR(300 MHz, CDCl3) -81.30 (t, JFF = 8.9 Hz 3F, CF3); -87.80 (m, 2F, SCF2); -121.05 (m, 2F, CF2); -125.60 (m, 2F, CF2) ppm Butyl Nonafluorobutyl Sulfide 1H NMR(300 MHz, CDCl3) 2.69 (t, J = 7.3 Hz, 2H, CH2); 1.66 (quintet, J = 7.6 Hz, 2H, CH2); 1.42 (sextuplet, J = 7.6 Hz, 2H, CH2); 0.93 (t, J = 7.3 Hz, 3H, CH3) 19F NMR(300 MHz, CDCl3) -81.35 (t, JFF = 8.5 Hz 3F, CF3); -87.68 (m, 2F, SCF2); -120.97 (m, 2F, CF2); -125.48 (m, 2F, CF2) ppm 2-Pyridyl Nonafluorobutyl Sulfide37 1H NMR(300 MHz, CDCl3) 8.47 (m, 1H, ArH); 7.62 (m, 2H, ArH); 7.11 (m, 1H, ArH) 19F NMR(300 MHz, CDCl3) -81.13 (t, JFF = 10.7 Hz 3F, CF3); -86.13 (m, 2F, SCF2); -120.35 (m, 2F, CF2); -125.70 (m, 2F, CF2) ppm 4-Pyridyl Nonafluorobutyl Sulfide 1H NMR(300 MHz, CDCl3) 8.51 (dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 2H, ArH); 7.37 (dd, J1 = 4.7 Hz, J2 = 1.75 Hz, 2H, ArH)

PAGE 41

2419F NMR(300 MHz, CDCl3) -81.20 (t, JFF = 10.5 Hz 3F, CF3); -86.00 (m, 2F, SCF2); -120.25 (m, 2F, CF2); -125.60 (m, 2F, CF2) ppm Phenyl Nonafluorobutyl Selenide34 19F NMR(300 MHz, CDCl3) -81.47 (t, JFF = 10.7 Hz 3F, CF3); -87.34 (m, 2F, SCF2); -119.14 (m, 2F, CF2); -126.05 (m, 2F, CF2) ppm

PAGE 42

25 CHAPTER 3 PERFLUOROALKYLATION OF IMINE TOSYLATES 3.1 Introduction Our laboratories have develope d methodologies for nucleophilic trifluoromethylation of numerous substrates, such as aldehydes12, cyclic sulfates15, benzoyl chlorides13 or disulfides16, using CF3I / TDAE system. Trifluoromethylamines are very interesting compounds because they can serve as synthetic intermediates to biologically active molecules, as shown in Figur es 3-1 and 3-2, where 3A can be used as pesticide38 and 3B as pain-reliever39. N S S O O CF3 N N N N H F3C NH F3C Figure 3-1. 3A Figure 3-2. 3B Previously trifluoromethylamines were only synthesized from precursors (i.e. ketones) already contai ning trifluoromethyl group.40-48 Prakash and coworkers have used Ruppert’s reagent (CF3TMS) with imine derivatives to prepare trifluoromethylamines49 and, in particular, chiral trifluoromethylamines.50,51 Indeed, the use of CF3TMS proved to be very effective for nucleophi lic trifluoromethylation of N-tosyl aldimines and N-(2methyl-2propane-sulfinyl)imines (Scheme 3-1), with the latter reactions exhibiting excellent diastereoselectivity.

PAGE 43

26 Simple alkylor aryl-substituted imin es are relatively unreactive toward nucleophilic trifluoromethylation, although Blaze jewski and co-workers were able to obtain modest to good yields for aryl sy stems by facilitating the reaction of CF3TMS using TMS-imidazole.52 As Prakash showed, the reactivit y of imines toward nucleophilic trifluoromethylation can be si gnificantly enhanced by using N-tosylimines, with the ptoluenesulfonyl group being removed from th e adduct by its treatment with phenol and 48% HBr to give the respec tive primary amine products.49 N Ph Ts CF3TMS N H Ts + TBAT THF, 0 5 oC 90% F3C Ph N Ph S CF3TMS N H S + TBAT THF, -55 oC 80% tBu O tBu O F3C Ph d.r >97% Scheme 3-1. Trifluoromethylation of imines using Ruppert’s reagent Using the same CF3I / TDAE methodology than deve loped for trifluoromethylation of aldehydes12, similar results53 to Prakash’s methods could be obtained (Scheme 3-2). Unfortunately, the analogous reactions with im ines bearing aliphati c substituents on the imine carbon did not produce the desired a dducts. Such attempts included the Ntosylimines of acetophenone, p-chloroacetophenone, cyclohe xanone, and hexanal. In contrast, aliphatic aldehydes had been re ported to provide adducts using Prakash’s CF3TMS methodology.49

PAGE 44

27 N Ar Ts N H Ts F3C Ar DMF, -30 0 oC 62-86% CF3I / TDAE (2.2 equiv.) N Ph S N H S DMF, -30 0 oC 66% Tol O Tol O F3C Ph d.r = 87:13 CF3I / TDAE (2.2 equiv.) Scheme 3-2. Trifluoromet hylation of imines using CF3I / TDAE Parallel to trifluoromethylamines, higher perfluoroalkylamines gather also much interest from pharmaceutical and agrochemical industries. For example, 3C can be used as a treatment against osteoporosis54 and 3D as a treatment of Alzheimer’s disease55. N H N N H OCH3CF2CF3tBu NC O N O HN O O N H O CF2CF3 Figure 3-3. 3C Figure 3-4. 3D Since in Chapter 2, we have shown that the CF3I / TDAE methodology could be extend to longer perfluoroalkyl iodide s, such as pentafluoroeth yl iodide or nonafluorobutyl iodide, we decided then to try to sy nthesize other perfluoroalkyl amines

PAGE 45

28 3.2 Synthesis of Tosyl Imines O R2 R 1H2NTs BF3.OEt2 or Ts-OH toluene, reflux N R2 R 1Ts + Scheme 3-1. Synthesis of tosyl imines The imines were easily prepared from aroma tic aldehydes and tosyl amine, as shown in Table 3-1. Unfortunately because of the el ectron withdrawing char acter of the tosyl group, tosyl amine was not reactive towards ke tones or alphatic aldehydes (entries 3.143.16) Table 3-1. Synthesis of tosyl imines entry R1 R2 Yield (%) 3.1 H 80 3.2 Me H 85 3.3 Cl H 85 3.4 F H 88 3.5 F3C H 80

PAGE 46

29 3.6 S H 30 3.7 O H 65 3.8 N CH3 H 95 3.9 CH3 0 3.10 CF3 0 3.11 C7H15 H 0 3.3 Pentafluoroethylation of Tosyl Imines N H Ar Ts CF3CF2I TDAE DMF -20 oC to RT CF2CF3ArN H H Ts ++ 12.2 2.2 Scheme 3-2. Nucleophilic pentaf luoroethylation of tosyl imines

PAGE 47

30 Table 3-2. Nucleophilic pentafl uoroethylation of tosyl imines Entry Ar Yield (%) Yield with CF3I53 (%) 3.1a 50 86 3.2a Me 70 84 3.3a Cl 70 78 3.4a F 72 81 3.5a F3C 68 3.6a S 55 3.7a O 60 3.8a N CH3 0

PAGE 48

31 In general, the reactions provide d similar results than with CF3I / TDAE system, with slightly lower yields. Fo r the case of 1-methylindol-3-i mine tosylate (entry 3.10a) the absence of reactivity may be explaine d by one of the resonance forms shown in Figure 3-1: with the carbon being on the position 3, the indole group becomes a good electron donating group, reducing hugely the electrophilic character of the carbon on the imine, thus the lack of reactivity towards C2F5 nucleophile. N N Ts N N Ts Figure 3-5. A resonance form of N-(N-methyl-3-indolylmethylene)-pmethylbenzenesulfonamide 3.4 Perfluorobutylation of Tosyl Imines Since good yields could be obtained with C2F5I, experiments with C4F9I were performed to extend further the methodology N H Ar Ts C4F9I TDAE DMF -20 oC to RT C4F9ArN H H Ts ++ 12.2 2.2 Scheme 3-3. Nucleophilic perfluorobutylation of tosyl imines In general the yields are lower than with C2F5I, but when the aryl group contains electron withdrawing elements, the yields are good and comparable to the ones from C2F5I (Table 3-3, entries 3.3b 3.5b). Furyl and thiophenyl tosyl imines are not very

PAGE 49

32 reactive but the yields are decent. Like as C2F5I, 1-methyl 3-indolyl tosyl imine is not reactive at all toward perfluoroalkyl ation. (Table 3-3, entry 3.8b) Table 3-3. Nucleophilic perfl uorobutylation of tosyl imines Entry Ar Yield (%) 3.2b Me 50 3.3b Cl 70 3.4b F 70 3.5b F3C 75 3.6b S 45 3.7b O 40 3.8b N CH3 0 Surprisingly the system C4F9I / TDAE provided rather good yields. Unlike with disulfides where C4F9I didn’t seem to be reactive enough (Chapter 2), the system C4F9I / TDAE provided sometimes yields similar to the ones from C2F5I / TDAE.

PAGE 50

333.5 Conclusion The nucleophilic trifluor omethylation methodology of tosyl imines using trifluoromethyl iodide and T DAE could be extended successf ully with pentafluoroethyl iodide and nonafluorobutyl iodide Different substrates were used and provided fair to very good yields. 3.6 Experimental Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus 300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with external tetramethylsilane (TMS, = 0.00 ppm) as a reference. Fluorine (19F) and proton (1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFCl3, = 0.00 ppm) as a reference for 19F NMR and TMS ( = 0.00 ppm) for 1H NMR. Deuterated chloroform (CDCl3) was used as NMR solvent. 3.6.1 Syntheses of Tosyl Imines Synthesis of N-(benzylidene)-p-methylbenzenesulfonamide (3.1) In a 100 mL one-neck round bottom flask, 4toluenesulfonamide (2.57g, 15 mmol) and benzaldehyde (1.52 mL 15mmol) was mixed in 40 mL of toluene. BF3EtO2 (0.15 mL) was added under N2. The flask was equipped with a Dean-Stark apparatus. The reaction mixture was refluxed for 14 hours, then cooled to room temperature and poured into 2M NaOH (10mL). The organic phase was washed with brine and water until neutral pH, dried over anhydrous magnesium sulfat e and the solvent was removed by vacuum. The oily residue was recrystallized from ethyl acetate to give a wh ite solid; yield: 3.11 g (80 %)

PAGE 51

341H NMR (CDCl3 9.03 (s, 1H, CH=N-Ts); 7.91 (m, 4H, ArH); 7.62 (m, 1H, ArH); 7.48 (m, 2H, ArH); 7.34 (m, 2H, ArH); 2.44 (s, 3H, CH3) ppm. Synthesis of N-(4-methylbenzylidene)-p-methylbenzenesulfonamide (3.2) The procedure and the workup are the same as the synthesis of N-(benzylidene)-pmethylbenzenesulfonamide, using 4-methyl benzaldehyde toyield 85 % of white solid 1H NMR (CDCl3 8.99 (s, 1H, CH=N-Ts); 7.88 (d, J = 8.1 Hz, 2H, ArH); 7.82 (d, J = 8.1 Hz, 2H, ArH); 7.34 (d, J = 8.1 Hz, 2H, ArH); 7.29 (d, J = 8.1 2H, ArH); 2.43 (s, 6H, CH3) ppm. Synthesis of N-(4-chlorobenzylidene)-p-methylbenzenesulfonamide (3.3) In a 100 mL one-neck round bottom flask, 4toluenesulfonamide (2.57g, 15 mmol) and 4-chlorobenzaldehyde (2.10g, 15mmol) was mixed in 40 mL of toluene. BF3EtO2 (0.15 mL) was added under N2. The flask was equipped with a Dean-Stark apparatus. The reaction mixture was refluxed for 14 hours, and then cooled to room temperature. White crystals precipitated upon cooling. The solid was filtered, then washed with water and dried under vacuum. Yield = 2.74 g (85 %) 1H NMR (CDCl3) 8.99 (s, 1H); 7.89 (d, J = 6.3 Hz, 2H); 7.86 (d, J = 6.3 Hz, 2H); 7.47 (d, J = 8.4 Hz, 2H); 7.35 (d, J = 8.4 Hz, 2H); 2.44 (s, 3H) ppm. Synthesis of N-(4-fluorobenzylidene)-p-methylbenzenesulfonamide (3.4) The procedure and the workup are the same as the synthesis of N-(benzylidene)-pmethylbenzenesulfonamide, using 4-fluorobenz aldehyde to yield 88% of white solid. 1H NMR (CDCl3 9.00 (s, 1H, CH=N-Ts); 7.96 (m, 2H, ArH); 7.89 (d, J = 8.4 Hz, 2H, ArH); 7.35 (d, J = 8.7 Hz, 2H, ArH); 7.19 (m, 2H, ArH); 2.44 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -101.59 (t, J = 8.7 Hz, 1F) ppm.

PAGE 52

35Synthesis of N-(4-trifluoromethylbenzylidene)-p-methylbenzenesulfonamide (3.5) Following the above procedure for 3.3, by using 4-trifluoromethylbenzaldehyde (2mL, 15mmol), provided 3.92 g (8 0% yield) of white solid. 1H NMR (CDCl3) 9.08 (s, 1H, CH=N-Ts); 8.04 (d, J = 8.1 Hz, 2H, ArH); 7.90 (d, J = 8.4 Hz, 2H, ArH); 7.75 (d, J = 8.1 Hz, 2H, ArH); 7.34 (d, J = 8.4 Hz, 2H, ArH); 2.45 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -63.83 (s, 3F, CF3) ppm. Synthesis of N-(2-thiophenylmethylene)-p-methylbenzenesulfonamide (3.6) In a 100 mL one-neck round bottom flask, 4toluenesulfonamide (2.57g, 15 mmol) and 2-thiophenecarboxaldehyde (1.4 mL, 15mmo l) was mixed in 40 mL of toluene. A catalytic amount of p-toluenesulfonic aci d monohydrate was added. The flask was equipped with a Dean-Stark apparatus. Th e reaction mixture was refluxed for 14 hours. The solution turned quickly dark green and black tar was formed. After 14 hours, charcoal was added to the hot solution and the mixture was stirred at 100 C for 1 hour and filtered while it was still hot. The solvent was removed under vacuum. Recrystallization from be nzene gave 1.07g (30%) of N-(2-thiophenylmethylene)-pmethylbenzenesulfonamide as a silvery gray solid 1H NMR (CDCl3 9.11 (s, 1H, CH=N-Ts); 7.87 (d, J = 8.7 Hz, 2H, ArH); 7.77 (d, J = 4.2 Hz, 2H, ArH); 7.34 (d, J = 8.7 Hz, 2H, ArH); 7.21 (m, 1H, ArH); 2.44 (s, 3H, CH3) ppm.

PAGE 53

36Synthesis of N-(2-furanylmethylene)-p-methylbenzenesulfonamide (3.7) The same procedure and workup as for N-(2-thiophenylmethylene)-pmethylbenzenesulfonamide, using 2-furfural (1.24mL, 15 mmol), gave 2.43 g (65%) of light brown solid. 1H NMR (CDCl3 8.81 (s, 1H, CH=N-Ts); 7.87 (d, J = 8.4 Hz, 2H, ArH); 7.74 (m,1H, ArH); 7.34 (m, 3H, ArH); 6.64 (dd, J = 5.1 and 3.3 Hz, 1H, ArH); 2.43 (s, 3H, CH3) ppm. Synthesis of N-(N-methyl-3-indolylmethylene)-p-methylbenzenesulfonamide (3.8) In a 100 mL one-neck round bottom flask, 4toluenesulfonamide (2.57g, 15 mmol) and N-methyl-3-indolcarbaxaldehyde (2.39 g, 15 mmol) was mixed in 40 mL of toluene. A catalytic amount of p-toluenesulfonic acid monohydrate was added. The flask was equipped with a Dean-Stark apparatus. Th e reaction mixture was refluxed for 14 hours. The solution became rapidly deep purple. After reflux, the reaction mixture was cooled to room temperature and the solvent was re moved in vacuo. The crude solid was recrystallized in benzene to gi ve 4.27 g (95% yield) of N-(N-methyl-3-indolylmethylene)-p-methylbenzenesulfonamide as a purple solid. 1H NMR (CDCl3 9.09 (s, 1H, CH=N-Ts); 8.30 (d, J = 6.9 Hz, 1H, ArH); 7.89 (d, J = 8.1 Hz, 2H, ArH); 7.74 (s, 1H, ArH); 7.33 (3, 5H, ArH); 3.88 (s, 3H, N-CH3); 2.40 (s, 3H, CH3) ppm. 3.6.2 General Procedure for Pentafluoroethylat ion of Tosyl Imines : Synthesis of Methyl-N-(3,3,3,2,2-pentafluoro-1-phenyl-propyl)-benzenesulfonamide (3.1a) In 25 mL, 3-neck-round bottom flask, equi pped with a total reflux condenser and N2, N-(benzylidene)-p-methylbenzenesulfonamide (0.259 g, 1 mmol) was disolved in 6 mL of anhydrous DMF. The solution was cooled at -30 C. Pentafluor oethyl iodide (0.6

PAGE 54

37 g, 2.4 mmol) was then introduced to the so lution. TDAE (0.51 mL, 2.2 mmol) was added around -20 C. The reaction mixture became quickly orange red. The reaction was allowed to warm up slowly to room temperat ure. And as the bath temperature reached 10 C white solid was formed. The reaction mixture was stirred at room temperature overnight. About 15 mL of 10% H2SO4 aqueous solution was added slowly to quench the reaction. As the acid solution was added, th e reaction mixture first became clear as the TDAE salt was dissolved in water. But the mixture became cloudy again as the product precipitated out. The solution was stirred for a while as more and more product precipitated. The solid was coll ected via filtration and dissolv ed in 30 mL of ether. The ether solution was washed 3 times with water to eliminate remaining DMF. The ether phase was dried over anhydrous MgSO4 and the solvent was removed by vacuum. The pale yellow crude product was re crystallized in toluene to af ford 0.189 g of a white solid. (50%) 1H NMR (CDCl3; 7.52 (d, J = 8.4 Hz, 2H, ArH); 7.24 (m, 3H, ArH); 7.10 (m, 4H, ArH); 5.48 (d, J = 9.9 Hz, 1H, NH); 4.97 (m, 1H, CH-N); 2.33 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -81.42 (s, 3F, CF2-CF3); -120.67 (dd, J1 = 291.9 Hz, J2 = 12.9 Hz, 1F, CF-CF3); -122.86 (dd, J1 = 291.6 Hz, J2 = 12.6 Hz, 1F, CF-CF3) ppm. Anal. Calcd for C16H14F8NO2S: C, 50.670; H, 2.694; N, 3.694. Found: C, 50.390; H, 3.591; N, 3.590.

PAGE 55

384-Methyl-N-[3,3,3,2,2-pentafluoro-(4-methyl-ph enyl)-propyl]-benzenesulfonamide (3.2a) White solid (70 % yield) 1H NMR (CDCl3; 7.52 (d, J = 8.1 Hz, 2H, ArH); 7.09 (d, J = 8.1 Hz, 2H, ArH); 7.02 (d, J = 8.4 Hz, 2H, ArH); 6.98 (d, J = 8.7 Hz, 2H, ArH); 5.50 (d, J = 9.9 Hz, 1H, NH); 4.92 (m, 1H, CH-N); 2.34 (s, 3H, CH3); 2.29 (m, 3H, CH3) ppm. 19F NMR (CDCl3) -81.42 (s, 3H, CF2-CF3); -120.72 (dd, J1 = 291.6 Hz, J2 = 12.6 Hz, 1F, CF-CF3); -122.78 (dd, J1 = 291.6 Hz, J2 = 12.6 Hz, 1F, CF-CF3) ppm. Anal. Calcd for C17H16F5NO2S: C, 51.908; H, 4.071; N, 3.562. Found: C, 51.716; H, 4.015; N, 3.503. 4-Methyl-N-[3,3,3,2,2-pentafluoro-(4-chloro-p henyl)-propyl]-benzenesulfonamide (3.3a) White solid (70 % yield) 1H NMR (CDCl3; 7.51 (d, J = 8.4 Hz, 2H, ArH); 7.21 (d, J = 8.4 Hz, 2H, ArH); 7.13 (d, J = 8.4 Hz, 2H, ArH); 7.05 (d, J = 8.4 Hz, 2H, ArH); 5.24 (d, J = 9.3 Hz, 1H, NH); 4.98 (m, 1H, CH-N); 2.38 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -81.39 (s, 3H, CF2-CF3); -120.35 (dd, J1 = 293.7 Hz, J2 = 13.5 Hz, 1F, CF-CF3); -123.33 (dd, J1 = 293.7 Hz, J2 = 13.5 Hz, 1F, CF-CF3) ppm. Anal. Calcd for C16H13ClF5NO2S: C, 46.398; H, 3.141; N, 3.383. Found: C, 46.255; H, 3.122; N, 3.355. 4-Methyl-N-[3,3,3,2,2-pentafluoro-(4-fluorophenyl)-propyl]-benzenesulfonamide (3.4a) White solid (72 % yield) 1H NMR (CDCl3; 7.52 (d, J = 8.4 Hz, 2H, ArH); 7.12 (m, 4H, ArH); 6.92 (t, J = 8.4 Hz, 2H, ArH); 5.37 (d, J = 9.3 Hz, 1H NH); 4.98 (m, 1H, CH-N); 2.36 (s, 3H, CH3) ppm.

PAGE 56

3919F NMR (CDCl3) -81.39 (s, 3H, CF2-CF3); -111.84 (m, 1F, ArF) -120.60 (dd, J1 = 291.3 Hz, J2 = 11.1 Hz, 1F, CF-CF3); -123.19 (dd, J1 = 293.7 Hz, J2 = 13.5 Hz, 1F, CFCF3) ppm. Anal. Calcd for C16H13F6NO2S: C, 48.363; H, 3.274; N, 3.526. Found: C, 48.259; H, 3.266; N, 3.333 4-Methyl-N-[3,3,3,2,2-pentafluoro-(4-trifluoromethyl-phenyl)-propyl]benzenesulfonamide (3.5a) White solid (68 % yield) 1H NMR (CDCl3 7.47 (d, J = 6.1 Hz, 2H, ArH); 7.45 (d, J = 6.1 Hz, 2H, ArH); 7.23 (d, J = 8.1 Hz, 2H, ArH); 7.06 (d, J = 8.1 Hz, 2H, ArH); 5.65 (d, J = 9.9 Hz, 1H, NH); 5.05 (m, 1H, CH-CF2); 2.31 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -63.54 (s, 3F, CF3); -81.41 (s, 3H, CF2-CF3); -119.54 (dd, J1 = 292.5 Hz, J2 = 14.4 Hz, 1F, CF-CF3); -123.91 (dd, J1 = 292.5 Hz, J2 = 14.4 Hz, 1F, CFCF3) ppm. Anal. Calcd for C17H13F8NO2S: C, 45.638; H, 2.908; N, 3.132. Found: C, 45.340; H, 2.833; N, 3.011. 4-Methyl-N-[3,3,3,2,2-pentafluoro-(2-thiophenyl )-propyl]-benzenesulfonamide (3.6a) White solid (55 % yield) 1H NMR (CDCl3 7.58 (d, J = 8.4 Hz, 2H, ArH); 7.25 (m, 1H); 7.17 (d, J = 8.4 Hz, 2H, ArH); 6.88 (m, 2H); 5.34 (m, 1H, CH-N); 5.018 (m, 1H, NH) 2.38 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -82.29 (s, 3H, CF2-CF3); -120.71 (dd, J1 = 289.2 Hz, J2 = 11.1 Hz, 1F, CF-CF3); -123.36 (dd, J1 = 289.2 Hz, J2 = 11.1 Hz, 1F, CF-CF3) ppm.

PAGE 57

40 Anal. Calcd for C14H12F5NO2S2: C, 43.636; H, 3.117; N, 3.636. Found: C, 43.578; H, 3.099; N, 3.620. 4-Methyl-N-[3,3,3,2,2-pentafluoro-(2-furanyl)-p ropyl]-benzenesulfonamide (3.7a) Light brown solid (60 % yield) 1H NMR (CDCl3 7.60 (d, J = 8.4 Hz, 2H, ArH); 7.19 (m, 3H); 6.21 (m, 2H, ring); 5.33 (d, J = 10.2 Hz, 1H, NH); 5.11 (m, 1H, CH-CF2); 2.38 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -82.02 (s, 3H, CF2-CF3); -120.72 (dd, J1 = 291.3 Hz, J2 = 13.2 Hz, 1F, CF-CF3); -122.33 (dd, J1 = 289.2 Hz, J2 = 13.1 Hz, 1F, CF-CF3) ppm. Anal. Calcd for C14H12F5NO3S: C, 45.528; H, 3.252; N, 3.790. Found: C, 45.246; H, 3.255; N, 3.747. 3.6.3 General Procedure for Perfluorobutylation of Tosyl Imines: Synthesis of 4Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(4-methyl-phenyl)-propyl]benzenesulfonamide (3.2b) In a 25 mL round bottom flask, connected with N2, N-(4-methylbenzylidene)-pmethylbenzenesulfonamide (0.273 g, 1 mmol) was disolved in 6 mL of anhydrous DMF. The solution was cooled at -30 C. Nonafluorobutyl iodide (0.38 mL, 2.2 mmol) was then introduced to the solution. TDAE (0.51 mL 2.2 mmol) was added around -20 C. The reaction mixture became quickly orange red a nd white solid was formed shortly after the addition of TDAE. The reaction was allowed to warm up slowly to room temperature. The reaction mixture was stirred at room temperature overnight. About 15 mL of 10% H2SO4 aqueous solution was added slowly to que nch the reaction. As the acid solution was added, the reaction mixture first became clear as the TDAE salt was dissolved in water. But the mixture became cloudy again as dark brown oil could be seen forming. The solution was stirred for several hours as more brown vicous oil was formed. 30 mL

PAGE 58

41 of ether were added to dissolve the oil. Th e two phases were separated and the ether solution was washed 3 times with water to eliminate remaining DMF. The ether phase was dried over anhydrous MgSO4 and the solvent was removed by vacuum. The pale yellow crude product was recrystallized in toluene to afford 0.189 g of a white solid. (50%) 1H NMR (CDCl3; 7.51 (d, J = 8.4 Hz, 2H, ArH); 7.09 (d, J = 8.1 Hz, 2H, ArH); 7.00 (m, 4H, ArH); 5.33 (d, J = 9.9 Hz, 1H, NH); 5.04 (m, 1H, CH-N); 2.34 (s, 3H, CH3); 2.29 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -81.43 (t, J = 9.9, 3F, CF2-CF3); -116.98 (dm, J1 = 301.5 Hz, 1F, CF-CH); -118.88 (dm, J1 = 301.5 Hz, 1F, CF-CH); -121.47 (m, 2F, CF2); 126.53 (m, 2F, CF2) ppm. Anal. Calcd for C19H16F9NO2S: C, 46.212; H, 3.243; N, 2.837. Found: C, 46.239; H, 3.185; N, 2.821 4-Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(4-chloro-phenyl)-propyl]benzenesulfonamide (3.3b) White solid (70 % yield) 1H NMR (CDCl3; 7.50 (d, J = 8.4 Hz, 2H, ArH); 7.18 (d, J = 8.7 Hz, 2H, ArH); 7.11 (d, J = 7.8 Hz, 2H, ArH); 7.04 (d, J = 8.4 Hz, 2H, ArH) 5.60 (d, J = 9.9 Hz, 1H, NH); 5.07 (m, 1H, CH-N); 2.37 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -81.41 (t, J = 11.1, 3F, CF2-CF3); -116.52 (dm, J1 = 304.8 Hz, 1F, CF-CH); -119.38 (d3, J1 = 304.8 Hz, 1F, CF-CH); -121.37 (m, 2F, CF2); 126.55 (m, 2F, CF2) ppm. Anal. Calcd for C18H13ClF9NO2S: C, 42.038; H, 2.530; N, 2.724. Found: C, 41.904; H, 2.457; N, 2.685.

PAGE 59

424-Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(4 -trifloromethyl-phenyl)-propyl]benzenesulfonamide (3.5b) White solid (75 % yield) 1H NMR (CDCl3; 7.47 (d, J = 8.1 Hz, 2H, ArH); 7.42 (d, J = 8.4 Hz, 2H, ArH); 7.22 (d, J = 8.1 Hz, 2H, ArH); 7.04 (d, J = 8.4 Hz, 2H, ArH) 5.99 (d, J = 10.2 Hz, 1H, NH); 5.16 (m, 1H, CH-N); 2.31 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -63.57 (s, 3F, Ar-CF3); -81.41 (t, J = 11.1 Hz, 3F, CF2-CF3); 115.84 (dm, J = 304.5 Hz, 1F, CF-CH); -119.77 (dm, J = 304.5 Hz, 1F, CF-CH); -121.33 (m, 2F, CF2); 126.52 (m, 2F, CF2) ppm. Anal. Calcd for C19H13F12NO2S: C, 41.654; H, 2.375; N, 2.558. Found: C, 41.751; H, 2.297; N, 2.553 4-Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(2-thiophenyl -phenyl)-propyl]benzenesulfonamide (3.6b) White solid (45 % yield) 1H NMR (CDCl3; 7.57 (d, J = 8.1 Hz, 2H, ArH); 7.23 (m, 1H, ring); 7.14 (d, J = 8.1 Hz, 2H, ArH); 6.90 (m, 1H, ring); 6.83 (m 1H, ring); 5.42 (m, 2H, CH-N and NH); 2.36 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -81.39 (t, J = 11.1 Hz, 3F, CF2-CF3); -116.69 (dm, J = 297.9 Hz, 1F, CF-CH); -119.22 (dm, J = 297.9 Hz, 1F, CF-CH); -121.47 (m, 2F, CF2); 126.52 (m, 2F, CF2) ppm. Anal. Calcd for C16H12F9NO2S2: C, 39.555; H, 2.472; N, 2.884. Found: C, 39.567; H, 2.421; N, 2.778

PAGE 60

434-Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(2-furanyl-phenyl)-propyl]benzenesulfonamide (3.7b) Brown solid (40 % yield) 1H NMR (CDCl3; 7.59 (d, J = 8.4 Hz, 2H, ArH); 7.26 (m, 1H, ring); 7.19 (d, J = 8.4 Hz, 2H, ArH); 6.21 (m, 2H, ring); 5. 42 (m, 2H, CH-N and NH); 2.38 (s, 3H, CH3) ppm. 19F NMR (CDCl3) -81.40 (t, J = 11.1 Hz, 3F, CF2-CF3); -116.69 (dm, J = 297.9 Hz, 1F, CF-CH); -119.22 (dm, J = 297.9 Hz, 1F, CF-CH); -121.47 (m, 2F, CF2); 126.52 (m, 2F, CF2) ppm. Anal. Calcd for C16H12F9NO3S: C, 40.908; H, 2.557; N, 2.983. Found: C, 40.733; H, 2.446; N, 2.907

PAGE 61

44 CHAPTER 4 PERFLUOROAKYLATION OF ALDEHYDES AND KETONES 4.1 Introduction Along with trifluoromethyl alcohols, longer perfluoroalkyl alcohols are generating growing interests from industries, as one can notice the fast increase of the number of patented molecules containing perfluoroalkyl alcohol function in the past few years. These molecules can be used as fungicide56 (Figure 4-1) or insecticide.57 CF 2 Me F 3 C F S O O N N OH Figure 4-1. 4A56 : Fungicide (CF 2 ) 3 NC CF 3 F 3 C Cl Cl NH 2 N N CH OH Figure 4-2. 4B57 : insecticide Our laboratories have developed successfu lly nucleophilic trif luoromethylation of aldehydes and ketones by using CF3I / TDAE system12. Since the methodology could be extended for pentafluoroethyl iodide and nonafluorobut yl iodide for disulfides (Chapter 2) and tosyl imines (Chapter 3), the re search was then performed on aldehydes and ketones.

PAGE 62

454.2 Pentafluoroethylation of Aldehydes and Ketones The procedure for the pentafluoroethylat ion of aldehydes and ketones is very similar than the trifluor omethylation of aldehydes12. Since earlier studies on the C2F5I / TDAE system have shown that the resulting co mlplex is stable below -10 C (Chapter 2), the reaction could be perfo rmed at -15 or -10 C. R1R2O CF3CF2I DMF OH R1CF2CF3R2TDAE -15 oC to RT h 1 hr 1 eq2.2 eq2.2 eq RT, 12 hrs Scheme 4-1. Pentafluoroethyl ation of aldehydes and ketones By comparison to the yields obtained in trifluoromethylation, the products from pentafluoroethylation were obtai ned in very similar yields. Th e yields are generally lower except for fluorenone (entry 4.5) where the yield was 95 % compared to 73 % for trifluoromethylated product. The aromatic aldehydes provided high yields (entries 4.14.3). The yields from ketones products are d ecent, but this may be explained by a lower reactivity than aldehydes toward s nucleophilic reaction for ket ones. As expected, ketones or aldehydes bearing a hydrogen on -carbon resulted in low to ve ry low yields (entries 4.6 and 4.7). Butyraldehyde, that had already low yield for trifluoromethylation, provided only 5 % yield, which is not really interesti ng. These low yields can be explained by the fact that TDAE is also a st rong base and would readily depr otonate acid hydrogens in the substrates, creating enolates, in th e case of aldehydes and ketones.

PAGE 63

46 Table 4-1. Compared yields between pentafluoroethylati on and trifluoromethylation of aldehydes and ketones Entry Substrate Yield (%) Yield with CF3I12 (%) 4.1 O 90 Quant. 4.2 O 75 80 4.3 O OMe 80 83 4.4 O 95 73 4.5 O 55 68 4.6 O 50 50 4.7 O 5 15

PAGE 64

474.3 Perfluorobutylation of Aldehydes and Ketones Since nucleophilic pentafluoroethylati on of aldehydes and ketones with C2F5I / TDAE system could provide good yields and comparable to trifluoromethylation with CF3I / TDAE system, the methodology was extended with C4F9I. R1R2O C4F9I DMF OH R1C4F9R2 TDAE -20 oC to RT h 1 hr 1 eq2.2 eq2.2 eq RT, 12 hrs Scheme 4-2. Nucleophilic perfluor obutylation of al dehydes and ketones The yields obtained are very low: 35 % for benzaldehyde and 20 % for cyclohexanone. Similar low reactivity of C4F9I / TDAE system was already observed in the case of disulfides (Chapt er 2). The fact that the C4F9I / TDAE complex is not very stable and tends to decompose shortly after the addition of TDAE to the reaction mixture may explain this low reactivity. Moreover the Sun Lamp that provided the light irradiation produces a lot heat, this additional heat may be the cause of lower yields. Table 4-2. Perfluorobutylat ion of aldehydes and ketones Entry Substrate % yield 4.8 O 3558 4.9 O 2059

PAGE 65

484.4 Conclusion In the same manner than with disulfides and tosyl imines the C2F5I / TDAE system provided very similar yields than CF3I / TDAE system. However C4F9I / TDAE system proved to be not reactive enough towards alde hydes and ketones and provided really low yields. The CF3I / TDAE methodology could be successfully extended to C2F5I. But C4F9I seems to be the limit of this methodol ogy in nucleophilic perf luoroalkylation of aldehydes because the yields are so low that it is not interesting to develop further the reaction. 4.5 Experimental Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus 300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with external tetramethylsilane (TMS, = 0.00 ppm) as a reference. Fluorine (19F) and proton (1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFCl3, = 0.00 ppm) as a reference for 19F NMR and TMS ( = 0.00 ppm) for 1H NMR. Deuterated chloroform (CDCl3) was used as NMR solvent. 4.5.1 General Procedure of Pentafluoroeth ylation of Aldehydes and Ketones: Synthesis of 1-Phenyl-2,2,3,3,3-pentafluoropropan-1-ol (4.2) In 25 mL, 3-neck-round bottom flask, equi pped with a reflux condenser and N2, benzaldehyde (0.37 mL, 3.68 mmol) was diso lved in 10 mL of anhydrous DMF. The solution was cooled at -20 C and C2F5I (2.0 g, 8.1 mmol) was in troduce into the solution. Then TDAE (2 mL, 8.1 mmol) was added into the reaction mixture. The color of the reaction mixture became dark red as TDAE was added. The mixture was allowed to warm up slowly to room temperature. The reaction was irradiated by a Sun lamp for 1 hour. White solid was formed as the temperat ure of the bath reach ed –10 C. The reaction

PAGE 66

49 mixture was stirred at room temperature overnight. The orange solution was filtered and the solid was washed with diethyl ether. The DMF solution was hydrolyzed with water and was extracted with ether (3 times). The combined ether layers were washed with brine and dried over MgSO4. The solvent was removed and the crude product was purified by column chromatography to afford colorless liquid60 at 90 % yield 1H NMR (CDCl3, 300MHz) 7.45 -7.70 (m, 5H, ArH); 5.06 (m, 1H, CHCF2); 2.87 (s, 1H, OH) ppm. 19F NMR (CDCl3, 300 MHz) -81.90 (m, 3F, CF3), -122.80 (m, 1F, CF3CFF), 129.50 (m, 1F, CF3CFF) ppm. 1-Naphthyl-2,2,3,3,3-pentafluoropropan-1-ol (4.2) 1H NMR (CDCl3, 300MHz) 8.05 (d, J = 8.4 Hz, 1H, ArH); 8.0 – 7.82 m, 3H, ArH); 7.657.32 (m, 3H, ArH); 5.89 (m, 1H, CHCF2); 2.85 (s, 1H, OH) ppm 19F NMR (CDCl3, 300 MHz) = -81.54 (m, 3F, CF3), -118.15 (dd, J1 = 290.4 Hz, J2 = 20.7 Hz, 1F, CF2), -130.24 (dd, J1 = 290.4 Hz, J2 = 20.7 Hz, 1F, CF2) ppm 1,1,1,2,2-Pentafluoro-5-(2methoxy -phenyl)-pent-4-en-3-ol (4.3) 1H NMR (CDCl3, 300MHz) 7.45 (dd, J1 = 7.7 Hz, J2 = 1.8 Hz, 1H, ArH); 7.31 (m, 1H, ArH); 7.25 (d, J = 16.2 Hz, 1H, ArH); 6.95 (m, 1H, ArH); 6.87 (dd, J1 = 7.5 Hz, J2 = 0.9 Hz, 1H) 6.27 (dd, J1 = 16.2, Hz, J2 = 7.1 Hz, 1H); 4.66 (m, 1H, CHCF2); 3.87 (s, 3H, OCH3); 2.26 (s, 1H, OH) 19F NMR (CDCl3, 300 MHz) = -81.40 (m, 3F, CF3), -122.25 (AB, dd, J1 = 291 Hz, J2 = 9.9 Hz, 1F, CFF CF3); -129.12 (dd, J1 = 291 Hz, J2 = 9.9 Hz, 1F, CFFCF3) ppm

PAGE 67

509-Pentafluoroethyl fluoren-9-ol (4.4) 1H NMR (CDCl3, 300MHz) 7.67 (m, 4H, ArH); 7.48 (m, 2H, ArH); 7.36 (m, 2H, ArH); 3.01 (s, 1H, OH) 19F NMR (CDCl3, 300 MHz) = -78.62 (s, 3F, CF3), -121.29 (s, 2F, CF2) ppm 1,1-Diphenyl-2,2,3,3,3-pentafluoropropan-1-ol (4.5)61 19F NMR (CDCl3, 300 MHz) = -84.65 (s, 3F, CF3), -115.97 (s, 2F, CF2) ppm Pentafluoroethyl cyclohexan-1-ol (4.6)62 19F NMR (CDCl3, 300 MHz) = -78.17 (s, 3F, CF3), -126.25 (s, 2F, CF2) ppm 1,1,1,2,2-Pentafluorobutan-3-ol (4.7)63 19F NMR (CDCl3, 300 MHz) = -81.57 (m, 3F, CF3), -122.75 (m, 1F, CF3CFF), 131.40 (m, 1F, CF3CFF) ppm 4.5.2 General Procedure for Perfluorobutyl ation of Aldehydes and Ketones: Synthesis of 1-Phenyl-2,2,3,3,4,4,5,5,5-nonafluoropentan-1-ol In a 25 mL round bottom flask, connected N2, benzaldehyde (0.37 mL, 3.68 mmol) was disolved in 10 mL of anhydrous DMF. The solution was cooled at -30 C and C4F9I (0.75 mL, 8.1 mmol) was introduce into the solution via a syringe. Then TDAE (2 mL, 8.1 mmol) was added into the reaction mixt ure at -20 C. The color of the reaction mixture became dark red as TDAE was added. The reaction was irradiated by a Sun lamp.The mixture was allowed to warm up slow ly to room temperature. White solid was formed shortly after the addition of TDAE. The reaction mixture was stirred at room temperature overnight with the presence of iradiation. The orange solution was filtered and the solid was washed with diethyl ether. 20 mL of water were added to the filtrate the two layers were separated and the aqueous pha se was extracted with ether (3 times). The

PAGE 68

51 combined ether layers were wash ed with brine and dried over MgSO4. The solvent was removed by vacuum and the crude product wa s purified by column chromatography.

PAGE 69

52 CHAPTER 5 SYNTHESES AND STUDIES OF TETRAKIS(DIMETHYLAMINO)ETHYLENE ANALOGUES 5.1 Introduction Our laboratories have successfully de veloped methodologies for nucleophilic perfluoroalkylation of numerous subtrates.12,13,14,15,50 These methodologies consist in reducing perfluoroalkyl iodides with tetrakis(dimethyl amino)ethylene (TDAE), creating perfluoroalkyl anions which can undergo nucleophilic reaction s on different eletrophilic substrates. The mechanism of the reactions is still not totally understood. But it is known that as TDAE was introduced into the reac tion mixture containing perfluoroalkyl iodide and the substrate, TDAE formed a temperature-dependently stable complex with perfluoroalkyl iodide. As the reaction temperature rose above these critical temperatures (0 C for CF3I, -10 C for C2F5I and -20 C for C4F9I), the complex decomposed freeing perfluoroalkyl anion, whic h only then reacted with th e substrate (Scheme 5-1). Substrate CF3I TDAE TDAE2+ CF3 I-complex Substrate product 0 oC -20 oC Scheme 5-1. CF3I / TDAE complex At this point, we have little knowledge about the complex and its decomposition. It is not sure whether the product resulted from an attack from a free perfluoroalkyl anion or from an intermediate form where TDAE is still involved. In the latter case, the presence of chirality in the complex would induce chirality in the final product. This

PAGE 70

53 would be particularly interesting in the case of reactions with aldehydes and ketones where an asymmetric carbon is created from the addition of perfluoroalkyl group to the carbonyl carbon. Since there is no preferen tial side of attack, the resulting perfluoroalkyl alcohol is a racemic mixture. The aim is then to synthesize analogue molecules to TDAE, conserving the tetrak is-amino ethylene part and possessing a structure that would be able to bear asymmetric carbons. Th e structure would be a cyclic analogue to TDAE containing asymmetric carbons, as shown in Figure 5-1. N N N N R R R R R' R'* Figure 5-1. Structure of a chiral TDAE analogue But the non chiral cyclic TDAE an alogue -1,3,1’,3’-tetraalkyl-2,2’bis(imidazolidene)(Figure 5-2), would be first synthesized and studied to see if comparable results than TDAE could be obtained. N N N N R R R R Figure 5-2. Non chiral TDAE analogue

PAGE 71

545.2 Syntheses of TDAE Analogues 5.2.1 Synthesis of 1,3,1’,3’-Tetraal kyl-2,2’-bis(imidazolidene) Two analogues were synthesized where R were methyl group a nd ethyl group. The one-pot synthesis invo lved reaction between N, N’-diethylethylene diamine or N,N’dimethylethylene diamine and N,N’-dimethylformamide dimethyl acetate64. The two reagents were dissolved in benzene and we re heated at 110 C for 4 hours then the product was collected via distil lation under reduced pressure. The resulting products are a pale yellow liquid for 1,3,1’,3’-tetraethyl-2,2 ’-bis(imidazolidene) and a pale yellow solid for 1,3,1’,3’-tetramethyl-2,2’-bis(imidazo lidene) with 40% yield for both products. NH NH R R N O O N N N N R R R R benzene reflux 4 hrs + 1 equiv.1.2 equiv.40% R = Me (5.1) orEt Scheme 5-2. Synthesis of 1,3,1’ ,3’-tetraalkyl-2,2’-bis(imidazolidene) 5.2.2 Synthesis of 1,3,1',3'-Tetramethyl -2,2'-bis(benzimidazolylidene) The other analogue we were interested in synthesizing was. N N N N Figure 5-3. benzimidazole TDAE analogue

PAGE 72

55 The synthesis of 1,3,1',3'-tetramethyl-2,2 '-bis(benzimidazolylidene)consisted in 3 steps. The first step is the synthesis of benzimidazole65 by reacting 1,2-diaminobenzene with formic acid. The reaction yielded 87%. The second step was the methylation of the amino groups with iodomethane to form 1,3-dimethyl-benzimidazolium iodide66 in 85% yield. The final step involved deprotonation of the hydrogen on imine carbon, producing a carbene which recombined to itself to form 1,3,1',3'-tetramethyl-2,2'-bis(benzimidazolylidene)67 resulting in a brown solid in 50%. HCO2H N H N+NH2NH2H2O+(5.2) N H N N N I 2 MeI + (5.3) N N I NaH THF 2 N N N N (5.4) Scheme 5-3. Multi-step synthesis of benzimidazole TDAE analogue

PAGE 73

565.3 Attempts of Trifluoromethyla tion using the TDAE Analogues 5.3.1 Attempts of Trifluoromethylati on using 1,3,1’,3’-Tetraalkyl-2,2’bis(imidazolidene) instead of TDAE The first attempts of nucleophilic trif luoromethylation using the imidazolidene TDAE analogue were performed in the sa me conditions than with TDAE: Anhydrous DMF was used as solvent and the analogue was added to the solution of benzaldehyde and CF3I at -20 C. The reaction mixture color di dn’t become deep red as it was always the case for TDAE. Instead the solution becam e darker yellow than the color of the analogue. But the mixture seemed to discolored back to pale yello w few moments later. The usual salt formation at 0 C for CF3I / TDAE couldn’t be seen by using the analogue. The solution stayed clear throughout the reaction process. 19F NMR revealed the presence of the tr ifluoromethylated adduct but in a yi eld lower than 10 %. Numerous reactions of optimization have been perf ormed but no more than 15 % of the product could be obtained. The “optimized” proce dure would introduce the imidazolidene TDAE analogue at -40 C, instead of -20 C, and th e temperature was kept at -40 C for more than 40 minutes before allowing the reaction mixture to warm up slowly to room temperature and stirred overnight. Th e reaction was irradiated for 12 hours. N N N N R R R R OH CF3CF3I O + + DMF h -40 oC to RT 15% 1 2.22.2 Scheme 5-4. Nucleophilic trifluoromethyl ation of benzaldehyde using 1,3,1’,3’tetraalkyl-2,2’-bis(imidazolidene)

PAGE 74

57 PhS-SPh N N N N R R R R CF3I + DMF -40 oC to RT PhS-CF3110 % 14.22.2 + based on equiv. of disulfides Scheme 5-5. Synthesis of phenyl trifluor omethyl sulfide by using imidazolidene TDAE analogue An attempt of trifluoromethylation of phe nyl disulfide was also performed. Only 110 % of phenyl trifluoromethyl thioether could be obtained, instead of nearly 200 % in the case of TDAE. But the thioether may be resulted from the SRN1 reaction of phenyl thiolate, formed by reduction of disulfide by TDAE analogue, with CF3I, since the analogue cannot efficiently cr eate trifluoromethyl anion. Scheme 5-6. Possible decomposition pathways for imidazolidene TDAE analogue

PAGE 75

58 The explanation of this lack of reac tivity of the TDAE analogue towards CF3I may be the fact that the cyclic TDAE analogues may give, after one-electron transfer to CF3I, the corresponding colored radical cation. It s eems that the radical cation is quite unstable since the color disappeared. By decomposing the radical cation would probably give the corresponding carbene and a ne w “smaller” radical cation.68 According to recent studies69, the carbene should not dimerize to fo rm back to the TDAE analogue but may react with O2 to form a cyclic urea or with benzaldehyde to form an intermediate that may give a bezoin condensation or the corresponding 2-benzoylimidazoline as final products.70 (Figure 5-7) Scheme 5-7. Reactivities of imid azolidene carbene towards benzaldehyde The cyclic voltammetry experiment was also performed on 1,3,1’,3’-tetraethyl2,2’-bis(imidazolidene). But the resulting gr aph didn’t show any reversible oxidation waves corresponding to the formation of stab le radical cations (Figure 5-4), whereas TDAE cyclic voltammetry graph shows reversibility.71

PAGE 76

59 Figure 5-4. Cyclic voltammogram for 1,3,1’ ,3’-Tetraethyl-2,2’-bis(imidazolidene), C = 3mM in DMF + 0.1 mM Et4NBF4 at 20 C, scan rate: 0.2V/s 5.3.2 Nucleophilic Trifluoromethylation of Phenyl disulfide using 1,3,1',3'Tetramethyl-2,2'-bis(benzimidazolylidene) The attempt of trifluoromethylation of phe nyl disulfide with 1,3,1',3'-Tetramethyl2,2'-bis(benzimidazolylidene) only provided trac es of phenyl trifluoromethyl sulfide. The analogue may be either too stable or may decompose directly to carbenes since the compound was synthesized via di merization oftwo carbenes. PhS-SPh N N N N CF3I + DMF -40 oC to RT PhS-CF31 4.2 2.2 + trace Scheme 5-8. Attempt of synthesis of phenyl trifluoromethyl sulfide by using 1,3,1',3'tetramethyl-2,2'-bis(benzimidazolylidene)

PAGE 77

605.4 Conclusion The idea of using chiral TDAE analogues to induce chirality in the final products would have been an interesti ng project since industries are looking for chiral fluorinated compounds as biologically active molecules. But the incapacity of these analogues to generate CF3 anion from CF3I didn’t allow us to develop further the idea. 5.5 Experimental Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus 300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with external tetramethylsilane (TMS, = 0.00 ppm) as a reference. Fluorine (19F) and proton (1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFCl3, = 0.00 ppm) as a reference for 19F NMR and TMS ( = 0.00 ppm) for 1H NMR. Deuterated chloroform (CDCl3) was used as NMR solvent. 5.5.1 Synthesis of 1,3,1’,3’-Tetraethyl-2,2’-bis(imidazolidene) (5.1) N,N-dimethylformamide dimethyl acetate (20 mL, 151 mmol) and N,Ndiethylethylene diamine (18.3 mL, 130 mmol) was dissolved in 80 mL of dry benzene. The solution was refluxed at 110 C for 3 hours. The azeotrope methanol/benzene was then distilled out. The remaining solution wa s cooled to the room temperature and the solvent was removed by vacuum. The product was distilled out under vacuum (bp = 8688 C/3 mmHg). Even though the melti ng point of 1,3,1’ ,3’-tetraethyl-2,2’bis(imidazolidene) is around 48 C, it remained a yellow liquid66. Yield = 50 % 5.5.2 Synthesis of Benzimidazole (5.2) In a 250 mL round bottom flasko-phenylenediami ne (27g, 0.25 mol) is treated with 15 mL of formic acid (17.3 g, 0.38 mol). The mixture was heated and refluxed at 100 C

PAGE 78

61 2 hours. After cooling, 10 % NaOH solution wa s added until the pH became just basic. The crude brown product was collected by filtrat ion and was rinsed with ice-cold water. The crude benzimidazole was then dissolved in 400 mL of boiling water. About 1 g of celite was added and the mixture was stirre d while boiling for 15 minutes before hot gravity filtration. The filtrate was allowed to cool slowly to room temperature and then was placed in an ice bath for 20 minutes. The product was filtered and washed with icecold water. The product was dried in the oven overnight to afford 25.69 g (87 % yield) of pale yellow powder65. MP = 171 – 173 C 1H NMR(CDCl3, 300 MHz) 8.10 (s, 1H, N-CH=N); 7.68 (m, 2H, ArH); 7.31 (m, 2H, ArH) 5.5.3 Synthesis of 1,3-Dimethyl-benzimidazolium iodide (5.3) In a 100 mL round bottom flask, 1.4 g of sodium was added in small portions in 25 mL of absolute ethanol. After all sodi um was dissolved, 7.1 g (60 mmol) of benzimidazole was added to the solution, followed by 25g of iodomethane (180 mmol) and 20 mL of benzene. The reaction mixture was refluxed for 15 hours. After the reflux, the solvents were removed by vacuum. And the crude was recrystallized with ethanol to yield 14.09 g (85 %) of 1,3dimethyl-benzimidazolium iodide as a pale pinkish solid66. 1H NMR(CDCl3, 300 MHz) 11.07 (s, 1H, N-CH=N); 7.72 (m, 4H, ArH); 4.28 (s, 3H, CH3); 4.27 (s, 3H, CH3) 5.5.4 Synthesis of 1,3,1',3'-Tetramethyl-2,2' -bis(benzimidazolylidene) (5.4) In a 250 mL round bottom flask, 1,3-dimethyl-benzimidazolium iodide (10.09 g, 34.8 mmol) was dissolved in 100 mL of fres hly distilled THF and sodium hydride (1.25

PAGE 79

62 g, 52.2 mmol) was added slowly to the solu tion. The mixture was stirred for 3 hours at the room temperature then 2 hours at 50 C The solvent was removed by vacuum. 50 mL of toluene was added to the dark brown resi due. The mixture was heated to boil and was hot-gravity filtered. The yellow filtrate wa s concentrated, n-hexane was added and the solution was cooled at -30 C for overnight The recrystallized light brown solid was filtered and dry to give 5.0 g of 1,3,1',3'-tetramethyl-2,2'-bis(benzimidazolylidene)67 (50 % yield)

PAGE 80

63 CHAPTER 6 DIMERIC DERIVATIVES OF OCTAFLUO RO[2,2]PARACYCLOPHANE (AF4) : A NEW SOURCE OF PERFLUOROALKYL RADICALS 6.1 Introduction 6.1.1 General Information Since their first designed synthesis in 1951,72 [2.2]paracyclophanes have been considered valuable compounds for testi ng theories of bonding, ring strain, and electron interactions.73-75 A number of methods have b een devised for the relatively convenient synthesis of the parent hydrocar bon, all of which requi re the use of high dilution methodology.76-78 In addition, it has been rec ognized since the mid-1960s that [2.2]paracyclophanes are useful chemical vapor deposition (CVD) precursors of thin film polymers, known in the industry as “parylenes”.79 Such parylenes are ideally suited for use as conformal coatings in a wide variety of applications, such as in the electronics, semiconductor, automotive, and medical indus tries. Parylene coatings are inert and transparent and have excellent barrier properties. Parylene N, which is generated from the parent hydrocarbon 1, has been found to be useful at temperatures up to 130 C. 1,1,2,2,9,9,10,10-Octafluoro[2.2]paracyclophane,80 the bridge-fluorinated version of 1 (and known in the industry as AF4), is th e CVD precursor of Parylene-HT polymer, poly(-tetrafluoro-p-xylylene). The Parylene-HT polymer combines a low dielectric constant (2.25)79 with high thermal stability (<1 wt % loss/2 h at 450 C), low moisture absorption (<0.1%), a nd other advantageous properties.81,82 With such properties and because its in vacuo depos ition process ensures conformality to

PAGE 81

64 microcircuit features and superior subm icron gap-filling capability, Parylene-HT continues to show considerable promise as an interlayer dielectric for on-chip high-speed semiconductor device interconnection. H2C H2C CH2CH2 F2C F2C CF2CF2 Figure 6-1. [2,2]-paracyclopha ne Figure 6-2. AF4 6.1.2 Synthesis of AF4 CF2Cl CF2Cl 4 eq Zn F2C F2C CF2CF2DMA, 100 oC 3h 60% Scheme 6-1. Synthesis of AF4 AF4 is produced in 60% yield in a reaction of Zn with 0.35 M p-bis(chlorodifluoromethyl)-benzene in DMA at 100 C.The mechanism of formation of AF4 is shown in Scheme 6-2. p-bis(chlorodifluoro methyl)-benzene is reduced first by zinc metal to p-xylylene intermediate 2, which reacts with itself to form dimer diradical 3. The two radicals reconnect to each other to form AF4. The unique chemical characteristics of 1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane (AF4) have been amply demons trated by a number of recent publications related to its synthesis,83-85 its chemical reactivity,86,87 and its role as the CVD precursor of the highly thermally stable, low-dielectr ic thin film polymer known as parylene-HT.8890

PAGE 82

65 CF2Cl CF2Cl CF2CF2F F F2C F2C F F AF4CF2F2C F F F F polymerization reduction bimolecular C-C bond formation 1 23-extended 3-syn rotation Scheme 6-2. Mechanism of formation of AF4 Because ring-substituted derivatives of AF 4 have the potential to produce parylene films with enhanced properties, efforts have been directed at the synthesis of compounds such as trifluoromethyl derivative (Figure 6-1). F2C F2C CF2CF2CF3 Figure 6-3. Trifluor omethyl-AF4 derivative Although 1 has been prepared by a traditi onal four-step synthetic sequence beginning with nitration of AF4,76 a more direct method base d on Sawada’s free-radical trifluoromethylation methodology ap peared potentia lly attractive.91 However, when trifluoroacetyl peroxide was allowed to decompose in the presence of AF4 in refluxing CH2Cl2, although the trifluoromethyl radical indeed added to one of the aromatic rings of AF4, no rearomatization to 1 was observed. Instead, the intermediate cyclohexadienyl

PAGE 83

66 radical 2 proved to be uncommonly stable, so stable that it survived sufficiently long to dimerize to a 57:43 mixture of the novel a nd structurally unprecedented diasteromeric products, d,land meso-3, in a total yield of 60% 6.2 Kinetic Studies of CF3-AF4-dimers 6.2.1 Synthesis of CF3-AF4-dimer F2C F2C CF2CF2 1 eq H2O2 (50%) 3eq (CF3CO)2O CH2Cl2F2C F2C CF2CF2CF3F2C F2C CF2CF2F3C 1) -78 OC to R.T. 2) reflux overnight 60% d,l : meso = 57:43 Scheme 6-3. Synthesis of CF3-AF4-dimer The dimer is formed via radical addition of CF3 • radical to AF4, forming a trifluoromethylated AF4 radical that read ily dimerizes into d,l and meso forms. F2C F2C CF2CF2F2C F2C CF2CF2F3C.2 CF3.F2C F2C CF2CF2CF3F2C F2C CF2CF2F3C22 Scheme 6-4. Formation of CF3-AF4-dimer

PAGE 84

67 The CF3 • radical was formed by thermal decomp osition of trifluoroacetyl peroxide, which was prepared in situ by reacting trif luoroacetic anhydride with hydrogen peroxide. (Scheme 6-5) Trifluoroacetic anhydride conve rts to trifluoro-pe roxy acetic acid which reacts with another molecule of trifluoroacetic anhydride to form trifluoroacetyl peroxide. The resulting peroxide decomposes thermally into 2 molecules of carbone dioxide and 2 molecules of the CF3 • radical. (CF3CO)2O + H2O2CF3CO3H+ CF3CO2H CF3CO3H + (CF3CO)2OCF3C(O)-O-O-C(O)CF3 + CF3CO2H CF3C(O)-O-O-C(O)CF32 CF3. + 2 CO2 Scheme 6-5. Mechanism of formation of CF3 • radical Figure 6-4. 19F NMR distinction examining the d,l and the meso forms of CF3-AF4dimers F2C F2C CF2CF2H F3C H F2C F2C CF2CF2CF3H H MESO F2C F2C CF2CF2F2C F2C CF2CF2CF3H H CF3H H D,L

PAGE 85

68 The two disateromers, d,l and meso forms, are distinguishable by 19F NMR, as shown in Figure 6-4, the multiplet peaks corresponding to the CF3 group having slightly different chemical shifts. They could also be separated by column chromatography. 6.2.2 Thermal Decomposition of the CF3-AF4-dimer The dimers are stable indefinitely at room temperature. But as they are heated, they decompose to regenerate back AF 4 and release 2 equivalents of CF3 • radical. Two different pathways for the mechanism of d ecomposition can be presented (Scheme 6-6). The decomposition can be stepwise where the di mer is first broken into two molecules of trifluoromethylated AF4 radical (A) and then CF3 • radicals were eliminated, forming back AF4 (path A) or the process is concerted and AF4 and CF3 • are formed in one single step (path B). F2C F2C CF2CF2F2C F2C CF2CF2F3CCF3F2C F2C CF2CF2F3C F2C F2C CF2CF22 CF3..2 2 +path Ap a t h BA Scheme 6-6. Two possible pathways for decomposition of CF3-AF4-dimer An experiment was performed to determine the mechanism of decomposition: the dimer was dissolved in acetonitrile with an excess of 1,4-cyclohexadiene, in a sealed

PAGE 86

69 NMR tube. 1,4-cyclohexadiene served as ra dical trap as it read ily quenches radicals present in the reaction by giving 2 hydrogen radical to form benzene. The reaction misture was heated above 160 C for several hour s. If the mechanism is the path B, the presence of 1,4-cyclohexadiene will not disturb anything and only AF4 will be formed but if it’s the path A, 1,4-cyclohexadiene wi ll trap trifluoromethyl ated AF4 radical A and A’ will be found instead of AF4 (Scheme 6-7). F2C F2C CF2CF2F2C F2C CF2CF2F3CCF3F2C F2C CF2CF2F3C F2C F2C CF2CF22 CF3H.2 2 +path AApath BF2C F2C CF2CF2F3C 2A'H Scheme 6-7. Resulting products from radical trapping in different possible mechanism pathway 19F NMR revealed a huge amount of AF4 in the reaction mixture but a small quantity of A’ could also be found. The pres ence of A’, even in a small amount, proved that the mechanism of the decomposition pr oceeds in a stepwise manner (path A). The presence of the large quantity of AF4 can be explained by the fact that the formation of AF4 from the radical A is much faster than the trapping by 1,4-cyclohexadiene.

PAGE 87

706.2.3 Kinetic Study of Homolysis of CF3-AF4-Dimers The study of the mechanism of the decomposition of the CF3-AF4-dimer showed that the rate determining step is the first step of the mechanism where the dimer broke down into two CF3-AF4 radical A. A kinetic study wa s the performed on the homolysis of the two diasteromers to determine rate constants and half lives at different temperatures and the activation energy of the reaction. F2C F2C CF2CF2F2C F2C CF2CF2F3CCF3 F2C F2C CF2CF2F3C F2C F2C CF2CF2F3C k.2 2 Scheme 6-8. Kinetic st udy of homolysis of CF3-AF4-Dimers The rate being first order, the slope of the plot of Ln of concentrations versus times would give the rate constant of the temp erature of experimentation, following the equation below: Ln([C]) = -k t The experiments consisted of dissolving one diasteromer in dry acetonitrile with an excess of 1,4-cyclohexadiene and a known amount of trifluorotoluene as internal standard in a sealed NMR tube. The tube was heated in an oil bath at fixed

PAGE 88

71 temperature. The tube was taken out of the o il bath regularly to measure the quantity of the dimer by 19F NMR and the time was measured. From all the data, a graph of Ln of concentration of dimer versus time was plotte d and the slope of the linear regression gave the rate constant k. The values of k at di fferent temperatures ar e shown in Table 6-1. Table 6-1. Rate constants of the 2 diasteromers of CF3-AF4-dimers Temperatures (C) k (d,l) (s-1) k (meso) (s-1) 140.1 7.37 x 10-6 8.62 x 10-6 151.0 2.24 x 10-5 2.81 x 10-5 160.7 7.14 x 10-5 8.50 x 10-5 170.3 1.57 x 10-4 3.21 x 10-4 179.7 4.55 x 10-4 4.94 x 10-4 The rate constants of the meso form were always greater than that of the d,l form but they are of the same order and pretty cl ose. The difference in rate constants between the two diasteromers seemed to decrease as the temperatures increase. From these rate constants values, the half -life times could be calculated according to the following equation: 22 / 1Ln k The values are shown in Table 6-2. Th ese half-life values confirmed the high stability of the compounds at room temperatur e: the half-lives of both dimers are above 22 hours at 140 C. But they decrease very rapi dly as the temperatur es increase, from more than 22 hours to 25 min in less than 40 C.

PAGE 89

72 Table 6-2. Half-life tim es of the homolysis of CF3-AF4-dimers Temperatures (C) (d,l) (meso) 140.1 26hrs 7 min 22hrs 20min 151.0 8hrs 36min 6hrs 51min 160.7 2hrs 42min 2hrs 16min 170.3 74 min 36min 179.7 25.4 min 23.4 min By using the Arrhenius equation, the activ ation energy of the homolysis could be obtained: ) exp( RT Ea A k K being the rate constant, Ea the activation energy and T the temperature in Kelvin.In the logari thmic form the equation beccomes: ) ( ) ( A Ln RT Ea k Ln By plotting Ln(k) versus 1/T, the slop e of the graph would give access to the activation energy.

PAGE 90

73 Figure 6-5. Arrhenius plot for the 2 diasteromers of CF3-AF4-dimers y = -20.059x + 36.901 R2 = 0.9876 y = -19.352x + 34.997 R2 = 0.9977 -12 -11.5 -11 -10.5 -10 -9.5 -9 -8.5 -8 -7.5 -7 2.202.252.302.352.40 1/T x 1000Ln K dl meso Linear (meso) Linear (dl)

PAGE 91

74 Table 6-3. Arrhenius plot data 1/T x 1000 Ln(k[d,l]) Ln(k[meso]) 2.42 -11.82 -11.66 2.36 -10.71 -10.48 2.31 -9.55 -9.37 2.26 -8.76 -8.04 2.21 -7.70 -7.61 Table 6-4. Activation parameters for CF3-AF4-dimers Ea (kcal/mol) Log A d,l-Form 38.43 15.20 meso-Form 39.83 16.02 6.3 Kinetic Studies of C2F5-AF4-dimers We were interested in study behaviors of AF4 dimers with a longer perfluoroalkylated chains. Ki netic studies of pentafluoroe thyl-AF4-dimers were then performed. 6.3.1 Synthesis of C2F5-AF4-dimers In the same manner as the synthesis of CF3-AF4-dimers, C2F5-AF4-dimers were formed from C2F5 • radical addition to AF4, the C2F5 • radical being formed from thermal decomposition of pentafluoropropionyl pero xide, formed in situ by reaction of perfluoropropionic anhydride with hydroge n peroxide. Since pe ntafluoropropionyl peroxide is much less stable than trifluor oacetyl peroxide, stirri ng overnight at room temperature was sufficient to decompose the peroxide.

PAGE 92

75F2C F2C CF2CF2 1 eq H2O2 (50%) 3eq (CF3CF2CO)2O CH2Cl2F2C F2C CF2CF2CF2CF3F2C F2C CF2CF2F3CF2C -78 OC to R.T. 50% d,l : meso = 55:45 Scheme 6-9. Synthesis of C2F5-AF4-dimers The dimer products are composed of two dias teromers, the d,l and meso forms, in a ratio of 55 and 45 respectively. They can be distinguished from each other by 19F NMR spectrum by examining the peaks of CF3 groups of the CF2CF3 chain, as shown in the Figure 6-6 Figure 6-6. 19F NMR distinction examining the d,l and the meso forms of C2F5-AF4dimers The structure of the meso form was determ ined by X-ray analysis and a perspective view is shown in Figure 6-7. F2C F2C CF2CF2F2C F2C CF2CF2CF2CF3H H CF2CF3H HD,L F2C F2C CF2CF2H F3CF2C H F2C F2C CF2CF2CF2CF3H HMESO

PAGE 93

76 Figure 6-7. Perspective view (ORTEP) of meso-C2F5-AF4-dimer 6.3.2 Kinetic Studies of the Homolysis of C2F5-AF4-dimers The kinetic studies on C2F5-AF4-dimer were performed using the same procedure as applied to the CF3-AF4-dimers. The rates constants are summarized in Table 6-5. Whereas for CF3-AF4-dimers, where the rate constants of the meso form werealways greater than that of the d,l form, for C2F5-AF4-dimers (with the exception of 118.8 C, where k(meso) is higher than k(d,l) ) the rates constants of d,l and meso forms are almost identical, with the tendency for d,l rate constants to be slightly greater.

PAGE 94

77 Table 6-5. Rate constants of the 2 diasteromers of C2F5-AF4-dimers Temperatures (C) k (d,l) (s-1) k (meso) (s-1) 118.8 1.16 x 10-6 1.80 x 10-6 130.5 5.02 x 10-6 4.63 x 10-6 139.6 9.53 x 10-6 1.00 x 10-5 145.3 2.31 x 10-5 2.14 x 10-5 151.3 4.16 x 10-5 4.10 x 10-5 156.4 5.86 x 10-5 5.83 x 10-5 161.0 1.09 x 10-4 1.10 x 10-4 The half-lives times at different temperatures are shown in Table 6-6. For C2F5AF4-dimers, the half-life times decrease ve ry rapidly, from more than 100 hours to around 70 minutes with only a 40 C change in temperatures. The decrease was much greater than was observed for the CF3-AF4-dimers. Table 6-6. Half-life times of the homolysis of C2F5-AF4-dimers Temperatures (C) (d,l) (meso) 118.8 166hrs 31min 107hrs 9min 130.5 38hrs 19min 41hrs 35min 139.6 20hrs 12min 19hrs 13min 145.3 8hrs 11min 9hrs 151.3 4hrs 38min 4hrs 42min 156.4 3hrs 17min 3hrs 18min 161.0 77min 80min

PAGE 95

78 An Arrhenius graph was plotted to obta in to the activation energies of the homolysis reaction. Table 6-7. Arrhenius plot data for C2F5-AF4-dimers 1/T x 1000 LnK (d,l) LnK (meso) 2.55 -13.67 -13.23 2.42 -11.56 -11.51 2.36 -10.09 -10.10 2.33 -9.74 -9.75 2.39 -10.67 -10.75 2.48 -12.20 -12.28 2.30 -9.13 -9.12 Table 6.8. Activation parameters for C2F5-AF4-dimers Ea (kcal/mol) Log A d,l-Form 35.65 13.90 meso-Form 33.01 12.60 The activation energies for C2F5-AF4-dimers are somewhat lower than that of the CF3AF4-dimers (38.43 kcal/mol for d, l and 39.83 kcal/mol for meso).

PAGE 96

79 Figure 6-8. Arrhenius plot of the 2 diasteromers of C2F5-AF4-dimers arrhenius plot y = -16.6237x + 29.0156 R2 = 0.9894 y = -17.9533x + 32.1679 R2 = 0.9941 -14.0 -13.5 -13.0 -12.5 -12.0 -11.5 -11.0 -10.5 -10.0 -9.5 -9.0 2.252.302.352.402.452.502.55 1/T *1000ln (k) d,l meso Linear (meso) Linear (d,l)

PAGE 97

80 6.4 Conclusion The AF4-dimers proved to be very intere sting compounds. Their stability at room temperature and their ability to release perfl uoroalkyl radicals at high temperatures make them an ideal source of perfluoroalkyl radical s where they can be used as initiators for polymerization reactions of fluorinated monomers92 in which a high purity is required since other initiators, such as AIBN, woul d introduce other func tional groups to the polymer chains 6.5 Experimental Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus 300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with external tetramethylsilane (TMS, = 0.00 ppm) as a reference. Fluorine (19F) and proton (1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFCl3, = 0.00 ppm) as a reference for 19F NMR and TMS ( = 0.00 ppm) for 1H NMR. Deuterated chloroform (CDCl3) was used as NMR solvent. 6.5.1 Synthesis of CF3-AF4-Dimer In 100 mL, 1-neck round bottom flask, 3g of AF4 (9 mmol) was dissolved in 25 mL of freshly distilled dichloromethane. Trifluoroacetic anhydride (4.2 mL, 30 mmol) were added. The solution was cooled at -78 C and 50% H2O2 (3.4 mL, 10 mmol) was introduced slowly via a syringe The reaction mixture was kept at -78 C for one hour and was allowed to warm to the room temper ature. The reaction was stirred at room temperature overnight and was then refluxed fo r at least 12 hours. White solid could be seen in the flask. After reflux, the mixtur e was cooled to room temperature and the

PAGE 98

81 solution was filtered. The crude was then purified86 and the two diasteromers were separated via column chromatography (hexanes/ CH2Cl2 : 9/1) 6.5.2 Kinetic Studies of CF3-AF4-Dimer 6.5.2.1 General procedure In a 5 inch NMR tube, 2 mg of one of the diasteromers of CF3-AF4-Dimer, 200 L of 1,4-cyclohexadiene and 0.6 L of -trifluorotoluene we re dissolved in 500 L of deuterated acetonitrile (CD3CN). A rubber septum was place on the tube and the solution was frozen at -78 C in dry ice / 2-propa nol bath. The tube was degassed under vacuum for several minutes. The NMR tube was flam ed sealed. The tube was immersed in a constant temperature bath for an appropriate time, then removed, cooled and analyzed by 19F NMR, with the concentration of the dimer being measured versus trifluorotoluene, used as internal standard. The rates were determined for each isomer at different temperatures.

PAGE 99

826.5.2.2 Kinetic data and graphs for CF3-AF4-Dimer at 140.1 C The following tables and figures show kinetic data and graphs for CF3-AF4-Dimer at 140.1 C. Table 6-9. Kinetic data of d,l-CF3-AF4-Dimer at 140.1 C d,l form Time (min) C.103 (mol/L) LnC 8 3.75 -5.59 279 3.11 -5.77 545 2.82 -5.87 744 2.59 -5.96 1206 2.11 -6.16 1533.5 1.83 -6.31 1926.5 1.50 -6.50 2360 1.24 -6.69 2691 1.12 -6.79 2923 1.01 -6.89 Table 6-10. Kinetic data of meso-CF3-AF4-Dimer at 140.1 C meso form Time (min) C.103 (mol/L) LnC 0 2.09 -6.17 254 1.84 -6.30 453 1.67 -6.40 915 1.31 -6.64 1242.5 1.12 -6.80 1635.5 0.89 -7.02 2069 0.70 -7.26 2400 0.62 -7.39 2632 0.54 -7.52

PAGE 100

83 Figure 6-9. Kinetic Graph of d,l-CF3-AF4-Dimer at 140.1 C Figure 6-10. Kinetic Graph of meso-CF3-AF4-Dimer at 140.1 C y = -0.00051719x 6.16656971 R2 = 0.99951338 -7.8 -7.6 -7.4 -7.2 -7.0 -6.8 -6.6 -6.4 -6.2 -6.0 050010001500200025003000 t (min)ln C y = -0.00044225x 5.62532632 R2 = 0.99751858 -7.1 -6.9 -6.7 -6.5 -6.3 -6.1 -5.9 -5.7 -5.5 0400800120016002000240028003200 t (min)Ln C

PAGE 101

846.5.2.3 Kinetic data and graphs for CF3-AF4-Dimer at 151.0 C The following table and figures show kinetic data and graphs for CF3-AF4-Dimer at 151.0 C. Table 6-11. Kine tic data of CF3-AF4-Dimers at 151.0 C d,l form Time (min) C.103 (mol/L) LnC 31 1.37 -6.59 65.5 1.26 -6.67 105.5 1.23 -6.70 178.5 1.10 -6.81 361.5 0.88 -7.03 925.5 0.41 -7.80 1115.5 0.313 -8.07 meso form Time (min) C.103 (mol/L) LnC 28.5 0.89 -7.03 69.5 0.85 -7.07 111.5 0.81 -7.12 219.5 0.68 -7.29 329.5 0.57 -7.47 893.5 0.21 -8.45 1083.5 0.15 -8.78

PAGE 102

85 Figure 6-11. Kinetic Graph of d,l-CF3-AF4-Dimer at 151.0 C Figure 6-12. Kinetic Graph of meso-CF3-AF4-Dimer at 151.0 C y = -0.00134211x 6.56228224 R2 = 0.99943388 -8.30 -8.10 -7.90 -7.70 -7.50 -7.30 -7.10 -6.90 -6.70 -6.50 020040060080010001200 t (min)ln C y = -0.00168423x 6.94225137 R2 = 0.99897753 -8.80 -8.70 -8.60 -8.50 -8.40 -8.30 -8.20 -8.10 -8.00 -7.90 -7.80 -7.70 -7.60 -7.50 -7.40 -7.30 -7.20 -7.10 -7.00 -6.90 020040060080010001200 t (min)ln C

PAGE 103

866.5.2.4 Kinetic data and graphs for CF3-AF4-Dimer at 160.7 C The following table and figures show kinetic data and graphs for CF3-AF4-Dimer at 160.7 C. Table 6-12. Kine tic data of CF3-AF4-Dimers at 160.7 C d,l form Time (min) C.103 (mol/L) LnC 19 2.59 -5.96 68 2.02 -6.20 97 1.84 -6.30 139 1.55 -6.47 196 1.19 -6.74 256 0.93 -6.98 meso form Time (min) C.103 (mol/L) LnC 0 1.92 -6.26 73 1.31 -6.64 122 0.99 -6.91 151 0.89 -7.02 193 0.73 -7.23 250 0.53 -7.55 310 0.39 -7.85

PAGE 104

87 Figure 6-13. Kinetic Graph of d,l-CF3-AF4-Dimer at 160.7 C Figure 6-14. Kinetic Graph of meso-CF3-AF4-Dimer at 160.7 C y = -0.00428300x 5.88704159 R2 = 0.99839077 -7.2 -7.0 -6.8 -6.6 -6.4 -6.2 -6.0 -5.8 050100150200250300 t (min)ln C y = -0.00510220x 6.26401120 R2 = 0.99904593 -8.0 -7.8 -7.6 -7.4 -7.2 -7.0 -6.8 -6.6 -6.4 -6.2 -6.0 050100150200250300350 t (min)ln C

PAGE 105

886.5.2.5 Kinetic data and graphs for CF3-AF4-Dimer at 170.3 C The following table and figures show kinetic data and graphs for CF3-AF4-Dimer at 170.3 C. Table 6-13. Kine tic data of CF3-AF4-Dimers at 170.3 C d,l form Time (min) C.103 (mol/L) LnC 15 2.17 -6.13 45 1.58 -6.45 61 1.38 -6.59 86 1.11 -6.81 116 0.84 -7.09 146 0.63 -7.37 190 0.41 -7.80 meso form Time (min) C.103 (mol/L) LnC 15 2.52 -5.98 45 1.28 -6.66 61 0.93 -6.98 77 0.69 -7.27 98 0.44 -7.72 113 0.35 -7.96 142 0.22 -8.43

PAGE 106

89 Figure 6-15. Kinetic graph of d,l-CF3-AF4-Dimers at 170.3 C Figure 6-16. Kinetic graph of meso-CF3-AF4-Dimers at 170.3 C y = -0.009413x 6.005657 R2 = 0.999477 -8.00 -7.80 -7.60 -7.40 -7.20 -7.00 -6.80 -6.60 -6.40 -6.20 -6.00 020406080100120140160180200 t (min)ln C y = -0.019281x 5.766482 R2 = 0.995762 -8.50 -8.30 -8.10 -7.90 -7.70 -7.50 -7.30 -7.10 -6.90 -6.70 -6.50 -6.30 -6.10 -5.90 020406080100120140160 t (min)ln C

PAGE 107

906.5.2.6 Kinetic data and graphs for CF3-AF4-Dimer at 179.7 C The following table and figures show kinetic data and graphs for CF3-AF4-Dimer at 179.7 C. Table 6-14. Kine tic data of CF3-AF4-Dimers at 179.7 C d,l form Time (s) C.103 (mol/L) LnC 109 3.62 -5.62 1012 2.35 -6.06 1920 1.61 -6.43 2829 1.11 -6.80 3740 0.67 -7.31 4348 0.53 -7.55 meso form Time (s) C.103 (mol/L) LnC 109 3.65 -5.61 712 2.77 -5.89 1620 1.79 -6.33 2225 1.31 -6.64 2838 0.95 -6.96 3446 0.71 -7.25

PAGE 108

91 Figure 6-17. Kinetic graph of d,l-CF3-AF4-Dimers at 179.7 C Figure 6-18. Kinetic graph of meso-CF3-AF4-Dimers at 179.7 C y = -0.00045479x 5.57046614 R2 = 0.99808643 -7.60 -7.40 -7.20 -7.00 -6.80 -6.60 -6.40 -6.20 -6.00 -5.80 -5.60 0500100015002000250030003500400045005000 t (s)ln C y = -0.00049442x 5.54362604 R2 = 0.99958986 -7.30 -7.10 -6.90 -6.70 -6.50 -6.30 -6.10 -5.90 -5.70 -5.50 05001000150020002500300035004000 t (s)ln C

PAGE 109

926.5.3 Synthesis of C2F5-AF4-Dimer The procedure for the synthesis of C2F5-AF4-Dimer was the same than for CF3AF4-Dimer, by using pentafluoropropionic anhy dride instead of trifluoroacetic anhydride and no reflux was needed. The reaction yielde d 40% as a 55:45 mixture of diasteromers, as determined by 19F NMR. The d,l and meso diasteromers were separated via column chromatography using hexanes/CH2Cl2 (9/1) as solvent. The x-ray analysis indicated that the minor isomer was the meso form. NMR for d,l-C2F5-AF4-dimer: 1H NMR (acetone-d6, 300 MHz): 7.83 (d, J = 8.1 Hz, 2H, ArH); 7.75 (m, 4H, ArH); 7.49 (d, J = 8.1 Hz, 2H, ArH); 6.34 (m, 2H); 6.13 (d, J = 7.2, 2H); 3.68 (m, 2H); 2.58 (m, 2H) 19F NMR (acetone-d6, 300 MHz): -83.59 (m, 6F, CF3); -108.90 (d, J = 260.4 Hz, 2F); -109.60 (d, J = 267.0 Hz, 2F); -110.14 (dd, J1 = 284.4 Hz, J2 = 59.4 Hz, 2F); -112.45 (d, J = -68.4 Hz, 2F); -113.83 (m, 6F); -116.27 (m, 6F) NMR for meso-C2F5-AF4-dimer: 1H NMR (acetone-d6, 300 MHz): 7.76 (m, 6H, ArH); 7.47 (d, J = 8.1 Hz, 2H, ArH); 6.20 (m, 4H); 3.81 (m, 2H); 2.69 (m, 2H) 19F NMR (acetone-d6, 300 MHz): -83.42 (m, 6F, CF3); -108.23 (d, J = 280.2 Hz, 2F); -109.11 (d, J = 282.6 Hz, 2F); -111.04 (dm, J = 262.8 Hz, 2F); -113.20 (m, 4F); 114.01 (dm, J = 269.4, 2F); -115.23 (d, J = 256.2, 2F) -115.96 (m, 6F)

PAGE 110

936.5.4 X-ray Structure of C2F5-AF4-Dimers X-ray experimental: Data were collected at 173 K on a Siemens SMART PLATFORM equipped with A CCD area dete ctor and a graphite monochromator utilizing MoK radiation ( = 0.71073 ). Cell parameters were refined using up to 8192 reflections. A full sphere of data (1381 frames) was collected using the -scan method (0.3 frame width). The first 50 frames we re remeasured at the end of data collection to monitor instrument and crysta l stability (maximum correction on I was < 1 %). Absorption corrections by integration were applied based on measured indexed crystal faces. The structure was solved by the Direct Methods in SHELXTL5, and refined using full-matrix least squares. The non-H atoms were treated anisotropically, whereas the hydrogen atoms were calculated in ideal pos itions and were riding on their respective carbon atoms. A total of 559 parameters were refined in the final cycle of refinement using 5920 reflections with I > 2 (I) to yield R1 and wR2 of 3.84% and 9.77%, respectively. Refinement was done using F2. Sheldrick, G. M. (1998). SHELXTL5 Bruker-AXS, Madison, Wisconsin, USA.

PAGE 111

94 Figure 6-19. X-ray structure of meso-C2F5-AF4-dimer

PAGE 112

95 Table 6-15. Crystal data and structure refinement Empirical formula C36 H16 F26 Formula weight 942.49 Temperature 193(2) K Wavelength 0.71073 Crystal system Monoclinic Space group P2(1)/c Unit cell dimensions a = 12.4560(6) = 90. b = 17.3580(9) = 111.396(2). c = 16.8135(9) = 90. Volume 3384.7(3) 3 Z 4 Density (calculated) 1.850 Mg/m 3 Absorption coefficient 0.208 mm -1 F(000) 1864 Crystal size 0.23 x 0.18 x 0.16 mm 3 Theta range for data collection 1.75 to 27.50. Index ranges -16 h 16, -22 k 22, -21 l 21 Reflections collected 29845 Independent reflections 7757 [R(int) = 0.0330] Completeness to theta = 27.50 99.8 % Absorption correction Analytical Max. and min. transmission 0.9690 and 0.9534 Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 7757 / 0 / 559 Goodness-of-fit on F 2 1.022 Final R indices [I>2sigma(I)] R1 = 0.0384, wR2 = 0.0977 [5920] R indices (all data) R1 = 0.0541, wR2 = 0.1086 Largest diff. peak and hole 0.369 and -0.322 e. -3 R1 = (||F o | |F c ||) / |F o | wR2 = [ w(F o 2 F c 2 ) 2 ] / w F o 2 2 ]] 1/2 S = [ w(F o 2 F c 2 ) 2 ] / (n-p)] 1/2 w= 1/[ 2 (F o 2 )+(0.049*p)2+1.8006*p], p = [max(F o 2 ,0)+ 2* F c 2 ]/3

PAGE 113

96 Table 6-16. Selected bond lengths [] and angles [] _____________________________________________________ C1-C1' 1.577(2) C4-C17 1.538(2) C17-C18 1.537(3) C4'-C17' 1.529(3) C17'-C18' 1.537(3) C2-C1-C6 108.75(13) C2-C1-C1' 110.64(13) C6-C1-C1' 114.76(13) C5-C4-C3 109.48(13) C5-C4-C17 114.04(14) C3-C4-C17 111.45(14) C18-C17-C4 114.84(15) C2'-C1'-C6' 108.89(13) C2'-C1'-C1 110.41(13) C6'-C1'-C1 113.87(13) C3'-C2'-C1' 123.66(15) 6.5.5 Kinetic Studies of C2F5-AF4-Dimers 6.5.5.1 General procedure The procedure for the kinetic experiments on C2F5-AF4-Dimers are the same than for CF3-AF4-dimers.

PAGE 114

976.5.5.2 Kinetic data and graphs of C2F5-AF4-Dimers at 118.8 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 118.8 C. Table 6-17. Kinetic data of C2F5-AF4-Dimers at 118.8 C D,l form Time (min) C.103 (mol/L) LnC 449 4.16 -5.48 932 4.04 -5.51 1125 3.98 -5.53 1561 3.86 -5.56 1889 3.77 -5.58 Meso form Time (s) C.103 (mol/L) LnC 449 3.41 -5.68 678 3.35 -5.70 932 3.27 -5.72 1125 3.17 -5.75 1889 2.93 -5.83

PAGE 115

98 Figure 6-20. Kinetic graph of d,l-C2F5-AF4-Dimers at 118.8 C Figure 6-21. Kinetic graph of meso-C2F5-AF4-Dimers at 118.8 C y = -6.9378E-05x 5.4493E+00 R2 = 9.9796E-01 -5.60 -5.58 -5.56 -5.54 -5.52 -5.50 -5.48 -5.46 -5.44 0200400600800100012001400160018002000 time (min)ln C y = -1.0782E-04x 5.6278E+00 R2 = 9.9408E-01 -5.85 -5.80 -5.75 -5.70 -5.65 -5.60 0200400600800100012001400160018002000 time (min)ln C

PAGE 116

996.5.5.3 Kinetic data and graphs of C2F5-AF4-Dimers at 125.7 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 125.7 C. Table 6-18. Kinetic data of C2F5-AF4-Dimers at 125.7 C D,l form Time (min) C.103 (mol/L) LnC 222 1.24 -6.70 772 1.00 -6.90 1649 0.74 -7.21 2032 0.66 -7.31 2972 0.449 -7.61 4206 0.33 -8.02 4632 0.30 -8.10 5532 0.23 -8.37 Meso form Time (min) C.103 (mol/L) LnC 222 0.43 -7.76 772 0.36 -7.93 1649 0.29 -8.16 2032 0.26 -8.26 2972 0.21 -8.48 4206 0.15 -8.83 5532 0.11 -9.11

PAGE 117

100 Figure 6-22. Kinetic graph of d,l-C2F5-AF4-Dimers at 125.7 C Figure 6-23. Kinetic graph of meso-C2F5-AF4-Dimers at 125.7 C y = -3.1439E-04x 6.6633E+00 R2 = 9.9816E-01 -8.50 -8.30 -8.10 -7.90 -7.70 -7.50 -7.30 -7.10 -6.90 -6.70 -6.50 0100020003000400050006000 t (min)lnC y = -2.5453E-04x 7.7280E+00 R2 = 9.9852E-01 -9.40 -9.20 -9.00 -8.80 -8.60 -8.40 -8.20 -8.00 -7.80 -7.60 0100020003000400050006000 t (min)lnC

PAGE 118

1016.5.5.4 Kinetic data and graphs of C2F5-AF4-Dimers at 130.5 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 130.5 C. Table 6-19. Kinetic graph of C2F5-AF4-Dimers at 130.5 C D,l form Time (min) C.103 (mol/L) LnC 554 1.05 -6.86 1132 0.83 -7.10 1724 0.70 -7.27 2670 0.53 -7.54 2930 0.50 -7.60 3908 0.38 -7.89 4276 0.33 -8.03 Meso form Time (min) C.103 (mol/L) LnC 554 1.73 -6.36 1132 1.41 -6.56 1724 1.20 -6.72 2670 0.93 -6.97 2930 0.86 -7.05 3908 0.68 -7.29 4276 0.59 -7.44

PAGE 119

102 Figure 6-24. Kinetic graph of d,l-C2F5-AF4-Dimers at 130.5 C Figure 6-25. Kinetic graph of meso-C2F5-AF4-Dimers at 130.5 C y = -3.0148E-04x 6.7271E+00 R2 = 9.9722E-01 -8.20 -8.00 -7.80 -7.60 -7.40 -7.20 -7.00 -6.80 050010001500200025003000350040004500 t (min)LnC y = -2.7780E-04x 6.2323E+00 R2 = 9.9751E-01 -7.60 -7.40 -7.20 -7.00 -6.80 -6.60 -6.40 -6.20 050010001500200025003000350040004500 t (min)LnC

PAGE 120

1036.5.5.5 Kinetic data and graphs of C2F5-AF4-Dimers at 139.6 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 139.6 C. Table 6-20. Kinetic data of C2F5-AF4-Dimers at 139.6 C D,l form Time (min) C.103 (mol/L) LnC 65 1.52 -6.49 145 1.46 -6.53 197 1.39 -6.58 286 1.34 -6.62 439 1.23 -6.70 823 0.98 -6.92 Meso form Time (min) C.103 (mol/L) LnC 65 3.49 -5.66 92 3.46 -5.67 197 3.16 -5.76 286 3.07 -5.78 439 2.80 -5.88 823 2.21 -6.12

PAGE 121

104 Figure 6-26. Kinetic graph of d,l-C2F5-AF4-Dimers at 139.6 C Figure 6-27. Kinetic graph of meso-C2F5-AF4-Dimers at 139.6 C y = -5.7181E-04x 6.4520E+00 R2 = 9.9832E-01 -6.95 -6.90 -6.85 -6.80 -6.75 -6.70 -6.65 -6.60 -6.55 -6.50 -6.45 0100200300400500600700800900 time (min)ln C y = -6.0131E-04x 5.6193E+00 R2 = 9.9652E-01 -6.20 -6.10 -6.00 -5.90 -5.80 -5.70 -5.60 0100200300400500600700800900 time (min)Ln C

PAGE 122

1056.5.5.6 Kinetic data and graphs of C2F5-AF4-Dimers at 145.3 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 145.3 C. Table 6-21. Kinetic data of C2F5-AF4-Dimers at 145.3 C D,l form Time (min) C.103 (mol/L) LnC 47.5 3.09 -5.78 97.3 2.93 -5.83 222.7 2.40 -6.03 348.0 2.08 -6.18 476.5 1.70 -6.38 608.4 1.43 -6.55 Meso form Time (min) C.103 (mol/L) LnC 47.5 1.36 -6.60 97.3 1.29 -6.65 222.7 1.08 -6.83 348.0 0.95 -6.96 476.5 0.78 -7.15 608.4 0.66 -7.32

PAGE 123

106 Figure 6-28. Kinetic graph of d,l-C2F5-AF4-Dimers at 145.3 C Figure 6-29. Kinetic data of meso-C2F5-AF4-Dimers at 145.3 C y = -0.001388131x 5.708866629 R2 = 0.998660941 -6.60 -6.50 -6.40 -6.30 -6.20 -6.10 -6.00 -5.90 -5.80 -5.70 0.0100.0200.0300.0400.0500.0600.0700.0 t (min)Ln C y = -0.001283123x 6.533644303 R2 = 0.998427577 -7.40 -7.30 -7.20 -7.10 -7.00 -6.90 -6.80 -6.70 -6.60 -6.50 0.0100.0200.0300.0400.0500.0600.0700.0 t (min)Ln C

PAGE 124

1076.5.5.7 Kinetic data and graphs of C2F5-AF4-Dimers at 151.3 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 151.3 C. Table 6-22. Kinetic data of C2F5-AF4-Dimers at 151.3 C D,l form Time (min) C.103 (mol/L) LnC 65.5 0.71 -7.25 107.0 0.63 -7.36 143.5 0.57 -7.47 175.5 0.53 -7.54 300.7 0.39 -7.85 361.0 0.34 -7.99 meso form Time (min) C.103 (mol/L) LnC 65.5 1.81 -6.31 107.0 1.65 -6.41 143.5 1.47 -6.52 175.5 1.39 -6.58 238.5 1.19 -6.74 300.7 1.02 -6.88 361.0 0.87 -7.05

PAGE 125

108 Figure 6-30. Kinetic data of d,l-C2F5-AF4-Dimers at 151.3 C Figure 6-31. Kinetic data of meso-C2F5-AF4-Dimers at 151.3 C y = -2.4964E-03x 7.0980E+00 R2 = 9.9899E-01 -8.10 -8.00 -7.90 -7.80 -7.70 -7.60 -7.50 -7.40 -7.30 -7.20 50100150200250300350400 t (min)ln C y = -2.4601E-03x 6.1523E+00 R2 = 9.9904E-01 -7.10 -7.00 -6.90 -6.80 -6.70 -6.60 -6.50 -6.40 -6.30 -6.20 50100150200250300350400 t (min)ln C

PAGE 126

1096.5.5.8 Kinetic data and graphs of C2F5-AF4-Dimers at 156.4 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 156.4 C. Table 6-23. Kinetic data of C2F5-AF4-Dimers at 156.4 C D,l form Time (min) C.103 (mol/L) LnC 0.0 3.29 -5.72 35.4 2.92 -5.84 94.3 2.36 -6.05 125.9 2.13 -6.15 176.9 1.83 -6.30 224.5 1.48 -6.52 262.8 1.30 -6.64 meso form Time (min) C.103 (mol/L) LnC 0.0 1.31 -6.64 35.4 1.18 -6.74 94.3 0.94 -6.97 125.9 0.85 -7.07 176.9 0.73 -7.22 224.5 0.59 -7.43 262.8 0.53 -7.55

PAGE 127

110 Figure 6-32. Kinetic graph of d,l-C2F5-AF4-Dimers at 156.4 C Figure 6-33. Kinetic graph of meso-C2F5-AF4-Dimers at 156.4 C y = -0.00351656x 5.71255775 R2 = 0.99816665 -6.80 -6.60 -6.40 -6.20 -6.00 -5.80 -5.60 0.050.0100.0150.0200.0250.0300.0 time (min)Ln C y = -0.00349577x 6.62845692 R2 = 0.99809669 -7.60 -7.40 -7.20 -7.00 -6.80 -6.60 -6.40 0.050.0100.0150.0200.0250.0300.0 time (min)ln C

PAGE 128

1116.5.5.9 Kinetic data and graphs of C2F5-AF4-Dimers at 161.0 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 161.0 C. Table 6-24. Kinetic data of C2F5-AF4-Dimers at 161.0 C D,l form Time (min) C.103 (mol/L) LnC 7.1 1.08 -6.83 32.5 0.89 -7.02 57.6 0.77 -7.17 77.0 0.66 -7.32 101.0 0.58 -7.45 125.5 0.50 -7.60 meso form Time (min) C.103 (mol/L) LnC 7.1 2.69 -5.92 32.5 2.25 -6.10 57.6 1.91 -6.26 77.0 1.67 -6.40 101.0 1.45 -6.54 125.5 1.23 -6.70

PAGE 129

112 Figure 6-34. Kinetic graph of d,l-C2F5-AF4-Dimers at 161.0 C Figure 6-35. Kinetic graph of meso-C2F5-AF4-Dimers at 161.0 C y = -6.5162E-03x 6.7972E+00 R2 = 9.9696E-01 -7.70 -7.60 -7.50 -7.40 -7.30 -7.20 -7.10 -7.00 -6.90 -6.80 -6.70 0.020.040.060.080.0100.0120.0140.0 t (min)Ln C y = -6.5753E-03x 5.8788E+00 R2 = 9.9925E-01 -6.80 -6.70 -6.60 -6.50 -6.40 -6.30 -6.20 -6.10 -6.00 -5.90 -5.80 0.020.040.060.080.0100.0120.0140.0 t (min)Ln C

PAGE 130

1136.5.5.10 Kinetic data and graphs of C2F5-AF4-Dimers at 165.9 C The following table and figures show kinetic data and graphs for C2F5-AF4-Dimers at 165.9 C. Table 6-25. Kinetic data of C2F5-AF4-Dimers at 165.9 C D,l form Time (min) C.103 (mol/L) LnC 7.4 1.49 -6.51 24.7 1.34 -6.62 51.4 1.01 -6.90 70.6 0.84 -7.08 96.1 0.64 -7.35 116.4 0.56 -7.49 153.5 0.42 -7.78 meso form Time (min) C.103 (mol/L) LnC 7.4 0.82 -7.11 24.7 0.74 -7.20 51.4 0.56 -7.49 70.6 0.48 -7.64 96.1 0.37 -7.90 116.4 0.33 -8.02 153.5 0.24 -8.35

PAGE 131

114 Figure 6-36. Kinetic graph of d,l-C2F5-AF4-Dimers at 165.9 C Figure 6-37. Kinetic graph of meso-C2F5-AF4-Dimers at 165.9 C y = -8.6562E-03x 7.0302E+00 R2 = 9.9681E-01 -8.60 -8.40 -8.20 -8.00 -7.80 -7.60 -7.40 -7.20 -7.00 0.020.040.060.080.0100.0120.0140.0160.0180.0 t (min)Ln C y = -9.0095E-03x 6.4363E+00 R2 = 9.9538E-01 -8.00 -7.80 -7.60 -7.40 -7.20 -7.00 -6.80 -6.60 -6.40 0.020.040.060.080.0100.0120.0140.0160.0180.0 t (min)Ln C

PAGE 132

115 GENERAL CONCLUSION The CF3I / TDAE methodology could be su ccessfully extended to longer perfluorinated alkyl iodides, su ch as pentafluoroethyl iodide or nonafluorobutyl iodide. In the case of disulfides, tosyl im ines, aldehydes or ketones as substrates, almost the same yields than CF3I / TDAE system could be obtained with C2F5I / TDAE system. These reactions represent efficient and easy ways to access to numerous biologically active compounds containing pentafluor oethyl groups. Whereas the C2F5I / TDAE system was very successful, mixed results were obtained with C4F9I / TDAE system. In most case the system provided low yields, thus less intere sting. These results showed the limit of the extension of the methodology. Longer perfluoroal kyl iodides may not be able to be used. Only in the tosyl imine case, the C4F9I / TDAE system could provide some good yields and the methodology might be able to be extended for longer chains. The TDAE analogue project would have b een very interesting if the analogues could have reacted the same way than T DAE. But unfortunately these analogues had totally different reactivities than TDAE. The AF4-dimers represent very interesting molecules, structurally and chemically. They are proved to be indefinitely stable at the room temperature but are able to free perfluoroalkyl radicals as they decompose at high temperatur es. This reaction can be used to initiate radical polymerizations.

PAGE 133

116 LIST OF REFERENCES 1. Russel, J.; Roques, N. Tetrahedron 1998, 54 13771-13782 2. Follas, B.; Marek, I; Normant, J.-F.; Jalmes, L. S. Tetrahedron Lett. 1998, 39 2973-2976 3. Kitazume, T.; Ishikawa, N. J. Am. Chem. Soc. 1985, 107 5186-5191 4. Prakash, G. K. S.; Krishnamurti, R.; Olah, G. A. J. Am. Chem. Soc. 1989, 111 393395 5. Singh, R. P.; Cao, G.; Kirchmeier, R. L.; Shreeve, J. M. J. Org. Chem. 1999, 64 2873-2876 6. Hagiwara, T.; Kobayashi, T.; Fuchikami, T.; Main Group Chem. 1997, 2 13-15 7. Wiedemann, J.; Heiner, T.; Mloston, G.; Prakash, G. K. S.; Olah, G. A. Angew. Chem. Int. Ed. 1998, 37 820-821 8. Billard, T.; Langlois, B. R. Tetrahedron Lett. 1996, 37 6865-6868 9. Burkholder, C. R.; Dolbier, W. R., Jr.; Mdebielle, M. J. Org. Chem. 1998, 63 5385-5394 10. Mdebielle, M.; Katsuya, K.; Dolbier, W. R., Jr. Synlett 2002, 9 1541-1543 11. Pawelke, G. J. J. Fluorine Chem. 1991, 52 229 12. A t-Mohand, S.; Takechi, N.; Medebielle, M.; Dolbier, W. R., Jr. Org. Lett. 2001, 3 4271-4273 13. Takechi, N.; A t-Mohand, S.; Medebielle, M.; Dolbier, W. R., Jr. Tetrahedron Lett. 2002, 43 4317-4319 14. Gao, Y.; Sharpless, K. B. J. Am. Chem. Soc. 1988, 110 7538-7539 15. Takechi, N.; A t-Mohand, S.; Medebielle, M.; Dolbier, W. R., Jr. Org. Lett. 2002, 4 4671-4672 16. Pooput, C.; Mdebielle, M. ; Dolbier, W. R., Jr. Org. Lett. 2004, 2, 301-303

PAGE 134

117 17. Okano, K.; He, L. (Mitsubishi Chemical Corp.). PCT Int. Appl. 2002 066423. Forat, G.; Mas, J.-M.; Saint-Jalmes, L. (Rhone-Poulenc Chimie). US Patent Appl. Publ. 2002 042542. 18. McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48 6555-6666 19. Boiko, V. N.; Shchupak, G. M.; Yagulpolskii, L. M. J. Org. Chem. USSR 1977, 13 972-975 20. Wakselman, C.; Tordeux, M. Chem. Commun. 1984, 793-794 21. Wakselman, C.; Tordeux, M. J. Org. Chem. 1985, 50 4047-4051 22. Umemoto, T.; Ishihara, S. Tetrahedron Lett. 1990, 31 3579-3582 23. Koshechko, V. G.; Kiprianova, L. A.; Fileleeva, L. I. Tetrahedron Lett. 1992, 33 6677-6678 24. Popov, V. I.; Boiko, V. N.; Yagulpolskii, L. M. J. Fluorine Chem. 1982, 21 365369 25. Quiclet-Sire, B.; Saicic, R. N.; Zard, S. Z. Tetrahedron Lett. 1996, 37 9057-9058 26. Roques, N. J. Fluorine Chem. 2001, 107 311-314 27. Blond, G.; Billard, T.; Langlois, B. R.; Tetrahedron Lett. 2001, 42 2473-2475 28. Toriyabe, K.; Ito, M.; Nishiyama, K.; Asahida, M.; Wada, N.; Yano, H.; Komatsu, M.; Fujisawa, T.; Shimau, T. Preparation of sulfur caontaining arythiazoles and insecticides. Jpn. Kokai Tokkyo Koho, 2000 29. Yoshida, K.; Wakita, T.; Katsuta, H.; Kai, A.; Chiba, Y.; Takahashi, K.; kato, H.; Kawahara, N.; Nomura, M.; Daido, H.; Maki, J.; Banba, S.; Kawahara, A. Preparation of aminobenzenecarboxam ide derivatives as insecticides. PCT Int. Appl. (2005) WO 2005021488 30. Okui, S.; Kyomura, N.; Fukuchi, T.; Tanaka, K. Preparation of pyrazole derivatives as pest control agents. PCT Int. Appl. (1998) WO 9845274 31. Bharati, J.; Tomoko, M.; Ritsu, K.; Ka tsuyoshi, S.; Hiroshinge, M.; Masaki, M. J. Fluorine Chem., 1995, 74 123-126 32. Wakselman C.; Tordeux, M. J. Org. Chem. 1985, 50 4047-4051 33. Roques, N. J. Fluorine Chem. 2001, 107 311-314 34. Magnier, E.; Vit, E.; Wakselman, C. Synlett 2001, 8 1260-1262 35. Barton, D. H. R.; Lacher B.; Zard, S. Z.; Tetrahedron 1986, 47 2325-2328

PAGE 135

118 36. Joglekar, B.; Miyake, T.; Kawase, R.; Shib ata, K.; Muramatsu, H.; Matsui, M. J. of Fluorine Chem. 1995, 74 123-126 37. Hartung, J.; Kneuer, R.; Laug, S.; Schmidt, P.; Spehar, K.; Svoboda, I.; Fuess, H. Eur. J. Org. Chem. 2003, 20 4033-4052 38. Tsuki, Y.; Shibata, M.; Kajiki, R.; F ukumoto, S.; Furuse, K.; Yamaji, K.; Takahashi, S.; Itou, Y.. Preparation of benzisothiazoline derivatives as agricultural or horticultural plant di sease control agents or pesticides. PCT Int. Appl. (2005), 75 pp. CODEN: PIXXD2 WO 2005018327 A1 20050303 CAN 142:280213 AN 2005:177800 39. Hollingworth, G. J.; Jones, B. A.; Mciver, E. G.; Moyes, C. R.; Rogers, L. Preparation of quinoxazolines and related derivatives vanilloid-1 receptor antagonists for treating pain. PCT Int. Appl. (2005), 108 pp. CODEN: PIXXD2 WO 2005047279 A1 20050526 AN 2005:451376 40. Pirkle, W. H.; Hanske, J. R. J. Org. Chem. 1977, 42 2436-2439. 41. Wang, Y.; Mosher, H. S. Tetrahedron Lett. 1991, 32 987-990. 42. Soloshonok, V. A.; Ono, T. J. Org. Chem. 1997, 62 3030-3031. 43. Osipov, S. N.; Golubev, A. S.; Sewald, N.; Burger, K. Tetrahedron Lett. 1997, 38 5965-5966. 44. Nelson, D. W.; Owens, J.; Hiraldo, D. J. Org. Chem. 2001, 66 2572-2582. 45. Gong, Y.; Kato, K. J. Fluorine Chem. 2002, 116 103-107. 46. Yong, K. H.; Chong, J. M. Org. Lett. 2002, 4 4139-4142. 47. Spanedda, M. V.; Ourevitch, M.; Crousse B.; Begue, J.-P.; Bonnet-Delpon, D. Tetrahedron Lett. 2004, 45 5023-5025. 48. Kochi, T.; Mukade, T.; Ellman, J. A. J. Synth. Org. Chem. Jpn. 2004, 62 128-139. 49. Prakash, G. K. S.; Mandal, M.; Olah, G. A. Synlett. 2001, 77-78. 50. Prakash, G. K. S.; Mandal, M.; Olah, G. A. Angew. Chem., Int. Ed. 2001, 40 589-590. 51. Prakash, G. K. S.; Mandal, M. J. Am. Chem. Soc. 2002, 124 6538-6539. 52. Blazejewski, J. C.; Anselmi, E.; Wilmshurst, M. P. Tetrahedron Lett. 1999, 40 5475-5478. 53. Wei, X.; Dolbier, W. R., Jr. J. Org. Chem. 2005, 70 4741-4745

PAGE 136

119 54. Bayly, C. I.; Black, C.; Leger, S.; Li, C. S.; McKay, D.; Mellon, C.; Gauthier, J. Y.; Lau, C.; Therien, M.; Truong, V.-L.; Green, M. J.; Hirschbein, B. L.; Janc, J. W.; Palmer, J. T.; Baskaran, C.. Cathepsin cysteine protea se inhibitors and their therapeutic use. PCT Int. Appl. (2003), 282 pp. CODEN: PIXXD2 WO 2003075836 A2 20030918 CAN 139:257284 AN 2003:737516 55. Flohr, A.; Galley, G.; Jakob-Roetne, R.; Kita s, E. A.; Peters, J.-U.; Wostl, W. Preparation of carbamic acid alkyl ester derivatives as. U.S. Pat. Appl. Publ. (2005), 38 pp. CODEN: USXXCO US 2005075327 A1 20050407 CAN 142:373708 AN 2005:303395 56. Gypser, A.; Kirstgen, R.; Sauter, H.; Bayer, H.; Cullmann, O.; Gewehr, M.; Grammenos, W.; Muller, B.; Ptock, A.; Tormo i Blasco, J.; Ammermann, E.; Grote, T.; Lorenz, G.; Strathmann, S.. Preparation of 5-hydroxypyrazoles as agrochemical fungicides. PCT Int. Appl. (2000), 41 pp. CODEN: PIXXD2 WO 2000020399 57. Kando, Y.; Kiji, T.; Noguchi, M.; Manabe, Y. Preparation of pyrazole derivatives as insecticides. Jpn. Kokai Tokkyo Koho (1996), 61 pp. CODEN: JKXXAF JP 08311036 A2 19961126 Heisei. CAN 126:89367 AN 1997:72214 58. Shen, Y.; Qi, M. J. Fluorine Chem 1994; 66 175-178 59. Rong, G.; Keese, R.; Tetrahedron Lett. 1990; 31 5617-5618 60. Russell, J.; Roques, N. Tetrahedron 1998, 54 13771-13782 61. Loomin, S.; Tamborsk, C. J. Fluorine Chem. 1982, 20 341-348 62. Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S. J. Org. Chem. 1991, 56 984989 63. Puy, M.; Poss, A. J.; Persichini, P. J.; Ellis, L. A. S. J. Fluorine Chem. 1994, 67 215-224 64. Wagner, E. C.; Millett, W. H., Org. Synth. Coll. Vol 11, 1943, 65 65. Goldwhite, H.; Kaminski, J.; Millhauser, G.; Ortiz, J.; Vargas, M. J. Organomet. Chem. 1986; 21-26 66. Yue, K.; Li, D.; Zhou, C.; Shi, Z.; Gu, H Huaxue Yanjiu Yu Yingyong 2002, 14 611-612. Journal written in Chinese 67. Cetinkaya, E; Hitchcock, P. B.; Kuecue kbay, H.; Lappert, M. F.; Al-Juaid, S. J. Organomet. Chem. 1994, 481 89-95

PAGE 137

120 68. Kurt S., Gnter B., Michael F., Carlo L., Robert L. Helv. Chim. Acta 2002, 85 1295-1326 69. Alder, R. W.; Blake, M. E; Oliva, J. M. J. Phys. Chem. A, 1999, 103 1120011211; Alder, R. W.; Blake, M. E.; Bortolotti C.; Bufali, S.; Butts, C. P.; Linehan, E.; Oliva, J. M.; Orpen, A. G.;Quayle, M. J. Chem. Commun. 1999, 3 241 70. Lappert, M. F.; Maskell, R. K. J. Chem. Soc., Chem. Commun. 1982, 11 580-581 71. Burkholder, C.; Dolbier, W. R., Jr.; Medebielle, M.; J. Org. Chem. 1998; 63, 53855394 72. Cram, D. J.; Steinberg, H. J. Am. Chem. Soc. 1951, 73 5691. 73. Boekelheide, V. Top. Curr. Chem. 1983, 113 87. 74. Cram, D. J. In Cyclophanes ; Keehn, P. M., Rosenfeld, S. M., Eds.; Academic Press: New York, 1983; Vol. 1, p 1. 75. Cram, D. J.; Cram, J. M. Acc. Chem. Res. 1971, 4 204-213. 76. Winberg, H. E.; Fawcett, F. S. Organic Syntheses ; Wiley: New York, 1973; Collect. Vol. V, pp 883-885. 77. Vogtle, F.; Neumann, P. Synthesis 1973, 85-103. 78. Ito, Y.; Miyata, S.; Nakatsuka, M.; Saegusa, T. J. Org. Chem. 1981, 46 1044-1045. 79. Gorham, W. F. J. Polym. Sci.: Part A-1 1966, 4 3027. 80. Chow, S. W.; Pilato, L. A.; Wheelwright, W. L. J. Org. Chem. 1970, 35 20-22. 81. Majid, N.; Dabral, S.; McDonald, J. F. J. Electron. Mater. 1989, 18 301-311. 82. Williams, K. R. J. Thermal Anal. 1997, 49 589-594. 83. Dolbier, W. R.; Asghar, M. A.; Pan, H. Q.; Celewicz, L. J. Org. Chem. 1993, 58 1827-1830. 84. Dolbier, W. R.; Rong, X. X.; Xu, Y. L.; Beach, W. F. J. Org. Chem. 1997, 62 7500-7502. 85. Dolbier, W. R., Jr.; Duan, J.-X.; Roche, A. J. Org. Lett. 2000, 2 1867-1869. 86. Roche, A. J.; Dolbier, W. R., Jr. J. Org. Chem. 1999, 64 9137-9143. 87. Roche, A. J.; Dolbier, W. R., Jr. J. Org. Chem. 2000, 65 5282-5290.

PAGE 138

121 88. Beach, W. F.; Lee, C.; Bassett, D. R.; Austin, T. M.; Olson, R. A. In Wiley Encyclopedia of Polymer Science and Technology ; Wiley: New York, 1989; Vol. 17, pp 990-1025. 89. Majid, N.; Dabral, S.; McDonald, J. F. J. Electron. Mater. 1989, 18 301-311. 90. Williams, K. R. J. Therm. Anal. 1997, 49 589-594. 91. Sawada, H.; Nakayama, M.; Yoshida, M.; Yoshida, T.; Kamigata,N. J. Fluorine Chem. 1990, 46 423-431. 92. Dolbier, W. R., Jr.; Abboud, K.; Ameduri, B.; Duan, J.-X.; J. Am. Chem. Soc.; 2000; 122 ; 12083-12086

PAGE 139

122 BIOGRAPHICAL SKETCH Chaya Pooput was born on September 22nd, 1977, in Bangkok, Thailand. In 1989, at the age of 12, he moved to Paris, France, to study, living with his aunt, Wanee Pooput. He graduated from high school, Lyce Michel et, receiving his Baccalaurat des Sciences in 1995 with honors. From 1995 to 1997, he spen t 2 years in Classes Prparatoires in Lyce Michelet, in order to prepare to the National Competitive Exams for entering a Grande cole, a National Higher School fo r Engineers. In 1997, he was accepted in l’cole Nationale Suprieure de Chimie de Montpellier (The Na tional Higher School of Chemistry of Montpellier), in Montpellier, south of France. During the 3 years he spent in L’cole de Chimie de Montpellier, he worked as trainee in several research laboratories. One of them was in Dr. William Do lbier’s laboratory at the Universitity of Florida, (Gainesville, Florida, USA) for 3 m onths in 1999, as a part of REU program and another was an industrial resear ch project at Solvay Resear ch and Development (Bussels, Belgium), for 7 months in 2000. After obtaining “le Diplme des Ingenieurs” (Diploma of Engineers, equivalent to a master’s degree) in 2000, Chaya was accepted in the graduate school of the University of Florida in the Department of Chemistry, and performed his research in Dr Dolbier’s laboratory. He obtained a master of Science degree in May 2004


Permanent Link: http://ufdc.ufl.edu/UFE0011625/00001

Material Information

Title: Syntheses and Studies of Perfluoroalkyl Substituted Compounds
Physical Description: Mixed Material
Copyright Date: 2008

Record Information

Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
System ID: UFE0011625:00001

Permanent Link: http://ufdc.ufl.edu/UFE0011625/00001

Material Information

Title: Syntheses and Studies of Perfluoroalkyl Substituted Compounds
Physical Description: Mixed Material
Copyright Date: 2008

Record Information

Source Institution: University of Florida
Holding Location: University of Florida
Rights Management: All rights reserved by the source institution and holding location.
System ID: UFE0011625:00001


This item has the following downloads:


Full Text












SYNTHESES AND STUDIES OF PERFLUOROALKYL SUBSTITUTED
COMPOUNDS
















By

CHAYA POOPUT


A DISSERTATION PRESENTED TO THE GRADUATE SCHOOL
OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT
OF THE REQUIREMENTS FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

UNIVERSITY OF FLORIDA


2005



























This dissertation is dedicated to my parents, Chatchawan and Payom Pooput.















ACKNOWLEDGMENTS

I express my deep gratitude to my advisor (Dr. William R. Dolbier, Jr.).

Throughout the years I have spent in his laboratory, I was able to acquire invaluable

knowledge to help me achieve my goals. Without his ideas, guidance and support, I

would not have been able to complete my research. I thank Dr. Samia Ait-Mohand for

helping me get started in research in my first year. I thank Dr Dolbier's group members

for their help. I thank David Duncan for helping me in experiments on TDAE analogue

project. I thank the Chemistry Department of the University of Florida for accepting me

in the graduate program. I thank all my friends, especially Valerie, Igor, Rachel, Rafal,

Janet, Jim, Gary, Rong and Hongfang for their support and friendship. I would like to

thank again Valerie for always being here for me, for cheering me up when I was down

and for sharing with me most of the wonderful moments I have in Gainesville. I also

thank Valerie's parents (Vale and Iris) for welcoming me in their home in Puerto Rico

and for giving me warmth and love that make me feel like I was a part of their family. I

thank Valerie's big family in Puerto Rico, Sonia, Mia, Nilda, Nelson and Nydia for their

love. I also thank my aunt Wanee for her support and love when I was in France. I thank

my sister for being who she is and for her love. Finally I am eternally grateful to my

parents. Because of their sacrifices, I was able to achieve this high level of education.

Their constant support and love gave me strength.
















TABLE OF CONTENTS

page

A C K N O W L E D G M E N T S ......... ...................................................................................... iii

LIST OF TABLES ........ ... .................................. ........ .. .................. viii

LIST OF FIGURES ............................... ... ...... ... ................. .x

LIST OF SCHEMES .......... .................................. ....... ....... xiii

ABSTRACT ........ .............. ............. ...... ...................... xvi

CHAPTER

1 IN TR O D U C TIO N ........................ .... ........................ ........ ..... ................

1.1 G general Inform ation .......................................................... ............... 1
1.2 P reviou s W ork ................... .... .......................... .. ......... ............ ..
1.2.1 Starting Point .......................................... ...... .... ........ .... .3
1.2.2 Preliminary Results in the Group.......................................4
1.2.3 New and Efficient Method for Synthesis of Trifluoromethyl
S u lfid e s .............................. ......................... ................ 5
1.2.4 New and Efficient Method for Synthesis of Trifluoromethyl
Selenides ............................................................. ............... 10

2 SYNTHESIS OF PERFLUOROALKYL THIO AND SELENOETHERS ..........12

2 .1 Introdu action .............................................. ........... ................ 12
2.2 Synthesis of Pentafluoroethyl Thioethers ............................................14
2.3 Synthesis of Pentafluoroethyl Selenoethers.............................................16
2.4 Synthesis of Perfluorobutyl Thioethers ...................................................17
2.5 Synthesis of Perfluorobutyl Selenoethers ............................................... 19
2.6 Conclusion ......................................... ................... .... ...... 19
2 .7 E xperim ental ................... .................. ...... ..... .......... .. .. ..... .....20
2.7.1 General Synthesis ofPentafluoroethyl Thio and Selenoethers :
Synthesis of Phenyl Pentafluoroethyl Sulfide.............................20
2.7.2 General Synthesis ofNonafluorobutyl Thio and Selenoethers :
Synthesis of Phenyl Nonafluorobutyl Sulfide.............................22










3 PERFLUOROALKYLATION OF IMINE TOSYLATES...............................25

3 .1 Intro du action ....... .. .... .. .. ...... ..................... ....................2 5
3.2 Synthesis of Tosyl Im ines........................................... ......................... 28
3.3 Pentafluoroethylation of Tosyl Imines...........................................29
3.4 Perfluorobutylation of Tosyl Im ines.................................. ... ..................31
3 .5 C o n c lu sio n ........................................................................................... 3 3
3.6 E xperim mental ............................ .. .... .............. ............... ............ 33
3.6.1 Syntheses of Tosyl Imines ............................ ...............33
3.6.2 General Procedure for Pentafluoroethylation of Tosyl Imines :
Synthesis of Methyl-N-(3,3,3,2,2-pentafluoro- 1 -phenyl-propyl)-
benzenesulfonamide (3.1a) ........................ .....................36
3.6.3 General Procedure for Perfluorobutylation of Tosyl Imines:
Synthesis of 4-Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(4-
methyl-phenyl)-propyl]-benzenesulfonamide (3.2b)...................40

4 PERFLUOROAKYLATION OF ALDEHYDES AND KETONES....................44

4 .1 In tro du ctio n ............... ................ ... ............... ............... 4 4
4.2 Pentafluoroethylation of Aldehydes and Ketones................ .......... 45
4.3 Perfluorobutylation of Aldehydes and Ketones ................. ............... 47
4 .4 C o n c lu sio n ........................................................................................... 4 8
4 .5 E xperim ental ................................................. ..... .............. ............... 48
4.5.1 General Procedure of Pentafluoroethylation of Aldehydes and
Ketones: Synthesis of 1-Phenyl-2,2,3,3,3-pentafluoropropan-1-
o l (4 .2 ) ............................................... ............... ... ............... 4 8
4.5.2 General Procedure for Perfluorobutylation of Aldehydes and
Ketones: Synthesis of 1-Phenyl-2,2,3,3,4,4,5,5,5-
nonafluoropentan-l-ol............... ................. .. ............. 50

5 SYNTHESES AND STUDIES OF
TETRAKIS(DIMETHYLAMINO)ETHYLENE ANALOGUES .........................52

5 .1 In tro d u ctio n .......................... .. .............. ............................. 5 2
5.2 Syntheses of TDAE Analogues ..................... .....................54
5.2.1 Synthesis of 1,3,1',3'-Tetraalkyl-2,2'-bis(imidazolidene) ............54
5.2.2 Synthesis of 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene).54
5.3 Attempts of Trifluoromethylation using the TDAE Analogues ................56
5.3.1 Attempts of Trifluoromethylation using 1,3,1',3'-Tetraalkyl-
2,2'-bis(imidazolidene) instead of TDAE.................................. 56
5.3.2 Nucleophilic Trifluoromethylation of Phenyl disulfide using
1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene) ..................59
5 .4 C o n c lu sio n ........................................................................................... 6 0
5.5 E xperim mental ......................... ..... .......... ... .... .... ........ ..... ......... .....60
5.5.1 Synthesis of 1,3,1',3'-Tetraethyl-2,2'-bis(imidazolidene) (5.1) ....60









5.5.4 Synthesis of 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene)
( 5 .4 ) ............................ ................................ ................ 6 1

6 DIMERIC DERIVATIVES OF OCTAFLUORO[2,2]PARACYCLOPHANE
(AF4) : A NEW SOURCE OF PERFLUOROALKYL RADICALS....................63

6.1 Introduction .......... .... ...... ..................................... .......... 63
6.1.1 General Information...................... ... ......................... 63
6.1.2 Synthesis of AF4...........................................64
6.2 K inetic Studies of CF3-AF4-dim ers................................... ... ..................66
6.2.1 Synthesis of CF3-AF4-dimer....................................... 66
6.2.2 Thermal Decomposition of the CF3-AF4-dimer........................68
6.2.3 Kinetic Study of Homolysis of CF3-AF4-Dimers........................70
6.3 Kinetic Studies of C2F5-AF4-dim ers ............................... ............... .74
6.3.1 Synthesis of C2F5-A F4-dim ers ................. .......... .....................74
6.3.2 Kinetic Studies of the Homolysis of C2F5-AF4-dimers.................76
6 .4 C o n c lu sio n ........................................................................................... 8 0
6 .5 E x p erim en tal ...................................................... ............ .................... 8 0
6.5.1 Synthesis of CF3-AF4-D im er ........... ..................... .................. 80
6.5.2 Kinetic Studies of CF3-AF4-Dimer ............................................ 81
6.5.2.1 G general procedure................................... ... ..................81
6.5.2.2 Kinetic data and graphs for CF3-AF4-Dimer
at 14 0 .1 oC ....................................................... 8 2
6.5.2.3 Kinetic data and graphs for CF3-AF4-Dimer at
1 5 1 .0 C ......................................................... 8 4
6.5.2.4 Kinetic data and graphs for CF3-AF4-Dimer at
1 6 0 .7 C ......................................................... 8 6
6.5.2.5 Kinetic data and graphs for CF3-AF4-Dimer at
1 7 0 .3 oC ......................................................... 8 8
6.5.2.6 Kinetic data and graphs for CF3-AF4-Dimer at
179 .7 C ...................................... ...... .. ....... 90
6.5.3 Synthesis of C2F -AF4-Dim er ....................................... .......... 92
6.5.4 X-ray Structure of C2F5-AF4-Dimers ................. ................. 93
6.5.5 Kinetic Studies of C2F5-AF4-Dimers...........................................96
6.5.5.1 G general procedure ..........................................................96
6.5.5.2 Kinetic data and graphs of C2F5-AF4-Dimers at
1 1 8 .8 C ...................................................... .. 9 7
6.5.5.3 Kinetic data and graphs of C2F5-AF4-Dimers at
12 5 .7 C ...................................................... .. 9 9
6.5.5.4 Kinetic data and graphs of C2F5-AF4-Dimers at
1 3 0 .5 oC ..................................................... .. 1 0 1
6.5.5.5 Kinetic data and graphs of C2F5-AF4-Dimers at
1 3 9 .6 C ..................................................... .. 1 0 3
6.5.5.6 Kinetic data and graphs of C2F5-AF4-Dimers at
14 5 .3 C ..................................................... .. 1 0 5
6.5.5.7 Kinetic data and graphs of C2F5-AF4-Dimers at
1 5 1 .3 C ..................................................... 1 0 7









6.5.5.8 Kinetic data and graphs of C2F5-AF4-Dimers at
1 5 6 .4 C ..................................................... .. 1 0 9
6.5.5.9 Kinetic data and graphs of C2F5-AF4-Dimers at
161.0 C ............................... .... ................. 111
6.5.5.10 Kinetic data and graphs of C2F5-AF4-Dimers at
165.9 C .................................... ....... ................ 113

GENERAL CON CLU SION ................................................................ ............... 115

LIST OF REFEREN CE S ..................................................................... ............... 116

B IO G R A PH ICA L SK ETCH ........... ..................................................... .....................122
















LIST OF TABLES


Table page

1-1 Trifluorom ethylation of disulfides ........................................ ......................... 7

1-2 Trifluoromethylation of disulfides using a higher amount of CF3I..........................

1-3 Synthesis of trifluoromethyl selenoethers .......................................... ..........11

2-1 Synthesis of pentafluoroethyl thioethers ............................................................... 15

2-2 Synthesis of pentafluoroethyl selenoethers ............................... ..................16

2-3 Synthesis of perfluorobutyl thioethers ...............................................................17

2-4 Synthesis of perfluorobutyl selenides .............................. .... .... ...................... 19

3-1 Synthesis of tosyl im ines............................................................................ .... ... 28

3-2 Nucleophilic pentafluoroethylation of tosyl imines..............................................30

3-3 Nucleophilic perfluorobutylation of tosyl imines .............. .... ...............32

4-1 Compared yields between pentafluoroethylation and trifluoromethylation of
aldehydes and ketones ......... ..... .. ..... .......................... .. ............. 46

4-2 Perfluorobutylation of aldehydes and ketones ............................... ................47

6-1 Rate constants of the 2 diasteromers of CF3-AF4-dimers.................... ........ 71

6-2 Half-life times of the homolysis of CF3-AF4-dimers.................... ..................72

6 -3 A rrh en iu s p lot d ata ........................................................................ ..................... 74

6-4 Activation parameters for CF3-AF4-dimers........................................ ...............74

6-5 Rate constants of the 2 diasteromers of C2F5-AF4-dimers ............. ...............77

6-6 Half-life times of the homolysis of C2F5-AF4-dimers ................ ........ ...........77

6-7 Arrhenius plot data for C2F5-AF4-dim ers ..................................... .................78









6.8 Activation parameters for C2F5-AF4-dimers.....................................78

6-9 Kinetic data of d,l-CF3-AF4-Dimer at 140.1 C..................................................... 82

6-10 Kinetic data of meso-CF3-AF4-Dimer at 140.1 C ...............................................82

6-11 Kinetic data of CF3-AF4-Dimers at 151.0 C............................ ............... 84

6-12 Kinetic data of CF3-AF4-Dimers at 160.7 C.............................................. 86

6-13 Kinetic data of CF3-AF4-Dimers at 170.3 C.............................................. 88

6-14 Kinetic data of CF3-AF4-Dimers at 179.7 C.............................................. 90

6-15 Crystal data and structure refinem ent.................................... ....................... 95

6-16 Selected bond lengths [A] and angles [] .......................... ............ .............. 96

6-17 Kinetic data of C2F5-AF4-Dimers at 118.8 C ................................. ... ................ 97

6-18 Kinetic data of C2F5-AF4-Dimers at 125.7 C .......................... .................99

6-19 Kinetic graph of C2F5-AF4-Dimers at 130.5 C............... ....................101

6-20 Kinetic data of C2F5-AF4-Dimers at 139.6 C ............................... ............103

6-21 Kinetic data of C2F5-AF4-Dimers at 145.3 C ............................... ............105

6-22 Kinetic data of C2F5-AF4-Dimers at 151.3 C ............................... ............107

6-23 Kinetic data of C2F5-AF4-Dimers at 156.4 C ............................... ............109

6-24 Kinetic data of C2F5-AF4-Dimers at 161.0 C ................. ... .................111

6-25 Kinetic data of C2F5-AF4-Dimers at 165.9 C ................. ... ................. 113

















LIST OF FIGURES

Figure page

1-1 Prozac ...................................................................

1-2 C eleb rex ....................................................... 1

1-3 Fipronil ..................... ................ ........................... .............................. 1

2-1 2A28: insecticide .................................................................................... ...... ..... ........ 12

2-2 2B29: insecticide ......................... ......... .. .. ........... ......... 12

2-3 2C 30: pesticide ........................ ...................... .. .. .... ........ ........ 12

3 1 3 A ..................................................................................2 5

3 -2 3 B .........................................................................2 5

3 -3 3 C .........................................................................2 7

3 -4 3 D ................... ...................2...................7..........

3-5 A resonance form of N-(N-methyl-3-indolylmethylene)-p-
m ethylbenzenesulfonam ide .............................................................. ..............31

4 -1 4 A 56 F u n g icid e ................................................................................................. 4 4

4-2 4B57 : insecticide ................................................................44

5-1. Structure of a chiral TD AE analogue ....................................................... 53

5-2 Non chiral TDAE analogue ......... .. ....................... 53

5-3 benzim idazole TDAE analogue ......................................................... 54

5-4 Cyclic voltammogram for 1,3,1',3'-Tetraethyl-2,2'-bis(imidazolidene), C =
3mM in DMF + 0.1 mM Et4NBF4 at 20 'C, scan rate: 0.2V/s..............59...............5

6-1 [2,2]-paracyclophane ................................................................. ..... ........64




x









6 -2 A F 4 .................................................................................. 6 4

6-3 Trifluoromethyl-AF4 derivative....................... .... ............................ 65

6-4 19F NMR distinction examining the d,l and the meso forms of CF3-AF4-dimers ...67

6-5 Arrhenius plot for the 2 diasteromers of CF3-AF4-dimers ....................................73

6-6 19F NMR distinction examining the d,l and the meso forms of C2F5-AF4-dimers ..75

6-7 Perspective view (ORTEP) of meso-C2F5-AF4-dimer ............... ...............76

6-8 Arrhenius plot for the 2 diasteromers of C2F5-AF4-dimers ...................................79

6-9 Kinetic Graph of d,l-CF3-AF4-Dimer at 140.1 C .............................. ...............83

6-10 Kinetic Graph of meso-CF3-AF4-Dimer at 140.1 C.........................................83

6-11 Kinetic Graph of d,l-CF3-AF4-Dimer at 151.0 C ................................................85

6-12 Kinetic Graph of meso-CF3-AF4-Dimer at 151.0 C .........................................85

6-13 Kinetic Graph of d,l-CF3-AF4-Dimer at 160.7 C .............................. ...............87

6-14 Kinetic Graph of meso-CF3-AF4-Dimer at 160.7 C .........................................87

6-15 Kinetic graph of d,l-CF3-AF4-Dimers at 170.3 C.............................. ...............89

6-16 Kinetic graph of meso-CF3-AF4-Dimers at 170.3 C ................... ................... 89

6-17 Kinetic graph of d,l-CF3-AF4-Dimers at 179.7 C.............................. ...............91

6-18 Kinetic graph of meso-CF3-AF4-Dimers at 179.7 C ................... ................... 91

6-19 X-ray structure of meso-C2F5-AF4-dimer..........................................................94

6-20 Kinetic graph of d,l-C2F5-AF4-Dimers at 118.8 oC .............................................98

6-21 Kinetic graph of meso-C2F5-AF4-Dimers at 118.8 C..................... ..........98

6-22 Kinetic graph of d,l-C2F5-AF4-Dimers at 125.7 C ......... .............................100

6-23 Kinetic graph of meso-C2F5-AF4-Dimers at 125.7 C.......................................100

6-24 Kinetic graph of d,l-C2F5-AF4-Dimers at 130.5 C ......... ............................102

6-25 Kinetic graph of meso-C2F5-AF4-Dimers at 130.5 C.......................................102

6-26 Kinetic graph of d,l-C2F5-AF4-Dimers at 139.6 C ......... .............................104









6-27 Kinetic graph of meso-C2F5-AF4-Dimers at 139.6 C .............. ..............104

6-28 Kinetic graph of d,l-C2F5-AF4-Dimers at 145.3 C ............................................106

6-29 Kinetic data of meso-C2F5-AF4-Dimers at 145.3 C .................. ...............106

6-30 Kinetic data of d,l-C2F5-AF4-Dimers at 151.3 C.................................. ...............108

6-31 Kinetic data of meso-C2F5-AF4-Dimers at 151.3 oC .................. ...............108

6-32 Kinetic graph of d,l-C2F5-AF4-Dimers at 156.4 C ............ .......... ............110

6-33 Kinetic graph of meso-C2F5-AF4-Dimers at 156.4 C .............. .............. 110

6-34 Kinetic graph of d,l-C2F5-AF4-Dimers at 161.0 C ....................................112

6-35 Kinetic graph of meso-C2F5-AF4-Dimers at 161.0 C ............................. 112

6-36 Kinetic graph of d,l-C2F5-AF4-Dimers at 165.9 C ............ .......... ............114

6-37 Kinetic graph of meso-C2F5-AF4-Dimers at 165.9 C .............. .............. 114
















LIST OF SCHEMES


Scheme p

1-1 Trifluoromethylation of benzaldehyde using fluoroform.................. ............ 2

1-2 Trifluoromethylation of benzaldehyde using trifluoromethyl zinc iodide .............2

1-3 Examples of trifluoromethylation reactions using Me3SiCF3................ ......... 3

1-4 Difluoromethylation reactions of aromatic aldehydes with TDAE .......................3

1-5 Difluoromethylation reactions of ethyl pyruvates with TDAE.............................4

1-6 Trifluoromethylation reaction of aldehydes and ketones.....................................4

1-7 Trifluoromethylation reaction of acyl chlorides ................................................... 4

1-8 Trifluoromethylation reaction of vicinal diol cyclic sulfate...................................5

1-9 Synthesis oftrifluoromethyl phenyl sulfide via SRN1 type reaction ......................5

1-10 Synthesis of trifluoromethyl phenyl sulfide using various sources of CF3 ............6

1-11 Synthesis of trifluoromethyl thioethers ............................................ ...............6

1-12 Efficient synthesis of trifluoromethyl sulfides .................... ......................... 7

1-13 M echanism of trifluoromethylation of disulfides............................... ... .................7

1-14 Another possible mechanism of formation of trifluoromethyl sulfide...................10

1-15 Synthesis of trifluoromethyl selenoethers ........................................... ..........10

2-1 Different methods for synthesis of perfluoroalkyl sulfides and selenides ..............13

2-2 Synthesis of trifluoromethyl sulfides with CF3I / TDAE methodology................... 13

2-3 Tandem CF3I process in the synthesis of trifluoromethyl sulfides ..........................14

2-4 Pentafluoroethylation of disulfides ................... ...................................... 15

2-5 Pentafluoroethylation of diselenides ................. ......... ...........................16









2-6 Synthesis of perfluorobutyl thioethers ............................................ ...............17

2-7 Synthesis of perfluorobutyl selenides .................. ................... ......................19

3-1 Trifluoromethylation of imines using Ruppert's reagent............... ...................26

3-2 Trifluoromethylation ofimines using CF3I / TDAE ......................... ............27

3-1 Synthesis of tosyl im ines........... ................. ............ ............... ............... 28

3-2 Nucleophilic pentafluoroethylation of tosyl imines..............................................29

3-3 Nucleophilic perfluorobutylation of tosyl imines .............. .... ...............31

4-1 Pentafluoroethylation of aldehydes and ketones.................................................45

4-2 Nucleophilic perfluorobutylation of aldehydes and ketones................................47

5-1 C F 3I / T D A E com plex ...................................................................... .................. 52

5-2 Synthesis 1,3,1',3'-tetraalkyl-2,2'-bis(imidazolidene) ............ ......... .........54

5-3 Multi-step synthesis of benzimidazol TDAE analogue.......................... .........55

5-4 Nucleophilic trifluoromethylation of benzaldehyde using 1,3,1',3'-tetraalkyl-
2,2'-bis(im idazolidene) ...................... .. .... ................................ ...........56

5-5 Synthesis of phenyl trifluoromethyl sulfide by using imidazolidene TDAE
a n a lo g u e .......................................................................... 5 7

5-6 Possible decomposition pathways for imidazolidene TDAE analogue................57

5-7 Reactivities of imidazolidene carbene towards benzaldehyde............................58

5-8 Attempt of synthesis of phenyl trifluoromethyl sulfide by using 1,3,1',3'-
Tetramethyl-2,2'-bis(benzimidazolylidene) .................................. .................59

6-1 Synthesis of A F4 ...... ......... ........................... .... .... .......... .......... .. .......... ...... .. 64

6-2 M echanism of form ation of AF4............................ ....................... ............... 65

6-3 Synthesis of CF3-A F4-dim er ........ .......................... .....................66

6-4 Form action of CF3-AF4-dimer.... ... ................................................................66

6-6 Two possible pathways for decomposition of CF3-AF4-dimer ............................68

6-7 Resulting products from radical trapping in different possible mechanism
p ath w ay ............................................................................. 6 9









6-8 Kinetic study of homolysis of CF3-AF4-Dimers..............................................70

6-9 Synthesis of C2F -AF4-dimers ........................................................................... 75















Abstract of Dissertation Presented to the Graduate School
of the University of Florida in Partial Fulfillment of the
Requirements for the Degree of Doctor of Philosophy

SYNTHESES AND STUDIES OF PERFLUOROALKYL SUBSTITUTED
COMPOUNDS

By

Chaya Pooput

August 2005

Chair: William R. Dolbier, Jr.
Major Department: Chemistry

Numerous compounds containing perfluoroalkyl groups are found to be

biologically active and are largely used in pharmaceutical and agrochemical areas.

Although several methods have been developed to incorporate trifluoromethyl group into

molecules, few are for longer perfluoroalkyl chains.

Nucleophilic trifluoromethylation has been largely developed in our laboratory by

using CF3I and Tetrakis(dimethylamino)ethylene (TDAE). This methodology was

extended to longer perfluoroalkyl iodides. Pentafluoroethyl iodide and nonafluorobutyl

iodide were used instead of trifluoromethyl iodide.

Reactions with disulfides and diselenides provided efficiently perfluoroalkyl thio-

and selenoethers, where, in most cases, both halves of the disulfides or diselenides were

converted quantitatively to thio or selenoethers.

Numerous pentafluoroethyl and nonafluorobutyl substituted amines could be

obtained in high yields by extending the methodology with tosyl imines.









Reactions with aldehydes and ketones provided good yields of pentafluoroethyl

substituted alcohols. But reactions using nonafluorobutyl iodide afforded low yields.

The extension of CF3I / TDAE methodology to longer perfluoroalkyl iodides will

allow us to access to a much larger number of biologically active compounds.

Several TDAE analogues were also synthesized but their reactivity towards CF3I is

completely different from TDAE and couldn't be used as TDAE substituents.

The syntheses and kinetic studies of perfluoroalkyl substituted AF4 dimers

provided valuable information on the use of these compounds as a stable source of

perfluoroalkyl radicals.















CHAPTER 1
INTRODUCTION

1.1 General Information

Pharmaceutical and agrochemical industries have a growing interest in compounds

containing perfluoroalkyl groups. Many new drugs contain trifluoromethyl groups:

examples are shown in Figures 1-1 and 1-2:

0 NHCH3
O N CF3

F3 H2N-S N



Figurel-1. Prozac Figurel-2. Celebrex



0
NC S-CF3


CCNH






CF3

Figurel-3. Fipronil

Among the several methods of incorporating the trifluoromethyl group into a

compound, one of the most useful is to generate in situ the unstable trifluoromethyl anion

to undergo nucleophilic trifluoromethylation on electrophilic substrates.









Various methods have been used to generate the trifluoromethyl anion: i) The

groups of Roques1 and Normant2 effectively performed nucleophilic trifluoromethylation

by using fluoroform (CF3H) in the presence of base; and ii) Kitazume3 used

trifluoromethylzinc iodide, prepared from trifluoromethyl iodide and zinc powder with

ultrasonic irradiation, as a trifluoromethylation reagent (Scheme 1-2).

O OH
CF3
+H 1) DMF, -50 C H
CF3H +
CFH 2)tBuOK, lh
3) AcOH, 0 C 20 C

Yield = 67%

Scheme 1-1. Trifluoromethylation of benzaldehyde using fluoroform

Curently the most commonly used source of the nucleophilic trifluoromethyl anion

is (trifluoromethyl)trimethylsilane (TMSCF3). In the past few years the groups of Prakash

and Shreeve have developed the method of generating in situ CF3 by reaction of

(trifluoromethyl)trimethylsilane (CF3TMS) with TBAF,4 CsF.5 Fuchikami6 reported that

trifluoromethylation reactions of carbonyl compounds can also be catalyzed by Lewis

bases, such as triethylamine, pyridine or triphenyl phosphine.

0 OH
CF3
H DMF H
+ CF3I + Zn
ultrasound


Yield = 72%

Scheme 1-2. Trifluoromethylation of benzaldehyde using trifluoromethyl zinc iodide

Extensive research had been performed on the use of this reagent with different

substrates, such as ketones, esters and disulfides.









+ OH

S+ Me3SiCF3 --- 0 H3O R R2
Rz R2 CsF
CF3

O 0

+ Me3SiCF3 HO
Rz OMe Bu4N+ RF CF3


R-S-S-R + Me3SiCF3 + Bu4N+ F THF R-S-CF3
0 C

Scheme 1-3. Examples of trifluoromethylation reactions using Me3SiCF35'7' 8

Even though (trifluoromethyl)trimethylsilane is a powerful trifluoromethylation

agent, it is very expensive. Our group wanted to find a less expensive and more direct

way to generate the nucleophilic CF3 anion.

1.2 Previous Work

1.2.1 Starting Point

Since 1998, with the collaboration of Dr. Maurice Medebielle, we have

demonstrated that tetrakis(dimethylamino)ethylene (TDAE) can be used as an efficient

reductant to generate nucleophilic difluoromethyl anions from chloro- and

bromodifluoromethyl compounds.9' 10

OH

RCF2X + ArCHO TDAE Ar H
DMF CF2R
CF2R
-20 0 to RT

Scheme 1-4. Difluoromethylation reactions of aromatic aldehydes with TDAE

OH
RCF2X + CH3COCO2Et TDAE H3C CO2Et
DMF
-20 o to RT CF2R










Scheme 1-5. Difluoromethylation reactions of ethyl pyruvates with TDAE

Pawelke earlier demonstrated that TDAE could be used with trifluoromethyl iodide

to prepare CF3TMS from TMSC1.1 With these results, we decided to use TDAE to

reduce trifluoromethyl iodide into trifluoromethyl anion.

1.2.2 Preliminary Results in the Group

With the aldehydes and ketones, the CF3I / TDAE system provided very good

yields, which were comparable to those obtained in analogous reactions using CF3TMS.12

0 OH
+ CF3I + TDAE hv, 12hrs O R+ R
R R2 -20 0 to RT 2
CF3
DMF
1 eq 2.2 eq 2.2 eq 53-95 %

Scheme 1-6. Trifluoromethylation reaction of aldehydes and ketones

Aryl acyl chlorides also underwent clean relations.13


0
SI1


F3C CF30


S 'Cl CF3I / TDAE I "
x -, DME X
-200 C to RT
48-98 %
RT, 2 hrs

Scheme 1-7. Trifluoromethylation reaction of acyl chlorides

Unfortunately the CF3I / TDAE system was not successful in reactions with

epoxides. But in 1988 Gao and Sharpless demonstrated that vicinal diol cyclic sulfates

could be used as epoxide equivalents, with a higher reactivity.14


O 0 + + 20% H2S04 HO CF3 F3C O
S+ CF3I + TDAE 3C ./
THF +
20 C t ROT 55%


)H

1%


5 hrs


1 eq 2.2 eq 2.2 eq


HO I
40%


X









Scheme 1-8. Trifluoromethylation reaction of vicinal diol cyclic sulfate

The reaction is highly regioselective because only 1% of the other isomer is

formed. Since the cyclic sulfate is highly reactive, competition between the iodide anion

and the trifluoromethyl anion occurred, which did not happen with other substrates.15

1.2.3 New and Efficient Method for Synthesis of Trifluoromethyl Sulfides

Aryl trifluoromethyl sulfides continue to attract much interest within

pharmaceutical companies, as witnessed by the significant number of process patent

applications recently submitted that are devoted to their preparation17. This interest

derives from the recognized potential of the SCF3 group to have a positive influence on

biological activity.

Diverse methods have been reported for the synthesis of aryl trifluoromethyl

sulfides18, but two seem to emerge as preferred methods.

The first is the SRN1 reaction of aryl thiolates with trifluoromethyl iodide or

bromide. Yagulpolskii was the first to report the reaction in 1977, using trifluoromethyl

iodide and UV irradiation19:

Ph-SH + CF3I NaOCH3, UV Ph-S-CF3 89%
CH3CN, 0 5 C

Scheme 1-9. Synthesis of trifluoromethyl phenyl sulfide via SRN1 type reaction

Wakselman and Tordeux used trifluoromethyl bromide in high pressure

(2 atm),20 21 and with other variations,22 23 this method is generally efficient when using

aryl thiolates but gives a much lower yield when using alkanethiolates.24

The other popular method involves the reaction of trifluoromethyl anion (generated

in situ by various methods) with aryl and alkyl disulfides:










PhS-SPh + CF3SiMe3 Bu4N F Ph-S-CF3 + Ph-S
THF, OC 3
32% s

PhS-SPh + CF3CO2K sulfolane, A Ph-S-CF3 + Ph-S

56% 25

84% 26

OH Ph tBuOK
PhS-SPh + F3C N N-' Ph-S-CF3 + Ph-S
H 27
87% 27

Scheme 1-10. Synthesis of trifluoromethyl phenyl sulfide using various sources of CF3

Although good yields can be obtained, the method suffers from the fact that half of

the disulfide is wasted in the process (formation of thiolates for the other half).

In our investigation16, the CF3I / TDAE system turned out to be a better method for

synthesis of trifluoromethyl sulfides than with Ruppert reagents (Table 1-1). Both aryl

and aliphatic disulfides provided near 100 % yield. The reaction is very fast only 2

hours of stirring at room temperature was sufficient to give a quantitative yield, as shown

in the entries 4 and 5.

R-S-S-R + TDAE + CF3I DMF R-S-CF3
0 OC to RT
RT several hr
1 eq. 2.2 eq 2.2 eq

Scheme 1-11. Synthesis oftrifluoromethyl thioethers









Table 1-1. Trifluoromethylation of disulfides
entry R Stirring time at RT M yi
entry R NMR yield
(hrs)
1 Phenyl 12 80

2 butyl 12 >98

3 ethyl 12 >98

4 butyl 4 >98

5 butyl 2 >98


R-S-S-R + TDAE + CF3I DMF R-S-CF3
0 oC to RT
180 200%
RT several hr
based of equivalents
1 eq. 2.2 eq 4.2 eq of disulfides


Scheme 1-12. Efficient synthesis of trifluoromethyl sulfides

It has been demonstrated that the mechanism of the reaction is as shown in the

Scheme 1-13.
0 20
TDAE + CF3I CF3 + I + TDAE2

R-S-S-R + CF3 -G R-S-CF3 + R-S

R-S0 + CF3I R-S-CF3 + I

Scheme 1-13. Mechanism of trifluoromethylation of disulfides

It occurred to us that CF3I could also be used as a substrate for reaction, via the

SRN1 mechanism, with the thiolate coproduct; thus, potentially enabling both halves of the

disulfide to be used in a one pot reaction, where CF3I would be used in two different

reactions, both of which lead to the same desired product. First TDAE reduces CF3I to

nucleophilic "CF3 ", which reacts with the disulfide to form trifluoromethyl sulfide and









thiolate. The resulting thiolate reacts with the excess of CF3I, in a SRN1 type mechanism

to create the second molecule of sulfide.

When more than 4.2 equivalents of CF31 are USed while the quantity of TDAE stays

at 2.2 equivalents, trifluoromethyl sulfides can be obtained at nearly 200% yield, based

on the number of equivalents of disulfides, as shown in the Table 1-2.

Table 1-2 Trifluoromethylation of disulfides using a higher amount of CF31


N
s benzothiazolyl group

*based of number of equivalents of disulfides

The entries 1 to 3 show that with 5 equivalents of CF3I, yields of nearly 200%

could be obtained whether with aryl disulfide or alkyl disulfide. The following entries are

attempts to optimize the procedure: 3.2 equivalents of CF3I did not seem to be sufficient,


Stirring time at RT
entry R Equiv. of CF3I Stirring time at NMR yield*
(hrs)

1 Phenyl 5 12 186

2 butyl 5 12 170

3 4-pyridyl 5 12 z 200

4 butyl 5 4 170

5 butyl 4.2 4 175

6 butyl 3.2 4 130

7 butyl 4.2 2 170

8 ethyl 4.2 2 180

9 2-pyridyl 4.2 2 180

10 t-butyl 4.2 12 0

11 2-nitrophenyl 4.2 2 185

12 benzothiazolyl 4.2 2 190

13 4-aminophenyl 4.2 12 20









since the yield was only 130% (entry 6) whereas more than 4.2 equivalents gave nearly

quantitative yields. Moreover 2 hours of stirring at room temperature was sufficient.

Although with t-butyl disulfide, we were unable to perform the trifluoromethylation

(entry 10), the result is nevertheless interesting because this shows a high influence of the

steric effect for the reaction. Moreover the lack of reactivity of t-butyl disulfide has been

noted previously, when CF3TMS was used as trifluoromethyl anion source.8 The entry 13

revealed another limitation of this methodology: CF3 anion being extremely unstable

reacts preferable first towards acidic protons, such as the ones present in the amino group

hence the very low yield for the reaction with 4-aminophenyl disulfide (Table 1-2, entry

13). All the groups containing acidic protons need then to be protected first before

undergoing trifluoromethylation with CF3I / TDAE method. In the case of 4-aminophenyl

disulfide, 4-nitrophenyl disulfide can be used and the nitro group can be reduced later to

obtain the amino group; the amino group can also be protected twice with BOC to avoid

the harsh conditions of reduction of nitro group.

It might be argued that these results could derive from reduction by TDAE of

disulfide to 2 equivalents of thiolate anion. The thiolate could react then with CF3I

proceeding entirely via SRN1 type reaction. If that were the case, the 2.2 equivalents of

CF3I along with 2.2 equivalents of TDAE should have been sufficient to obtain the high

yields observed in the Table 1-2. However, in the case where 2.2 equivalents of CF3I

were used (Table 1-1), yields never exceeded 100%. This probably means that CF3I is

reduced faster than the disulfides.










TDAE + R-S-S-R -- 2 R-S + TDAE2O

2R-S + 2CF31 2 R-S-CF3 + 2 1

Scheme 1-14. Another possible mechanism of formation of trifluoromethyl sulfide

Nevertheless, a control reaction was carried out to provide more definitive evidence

for the proposed dual mechanism synthetic process. CF3I (5 equiv.) and TDAE (2 equiv.)

were added first together at -200C so that TDAE would be totally oxidized by the

reaction with CF3I. The solution was then allowed to warm to -50C, at which time, n-

butyl disulfide was introduced. At this point there should be little if any TDAE remaining

to react with the disulfide. Despite this, the observed yield from this reaction was 160%,

which compares well with the 170% obtained when using the normal procedure (Table 1-

2, entry 5). This can be concluded that the reaction likely proceeds via the two-stage

process described earlier. These interesting results mean that the disulfides provide two

molecules of trifluoromethyl sulfides, which was never observed before in the other

methods.

1.2.4 New and Efficient Method for Synthesis of Trifluoromethyl Selenides

Since diselenides have similar reactivities than that of disulfides, reactions of

nucleophilic trifluoromethylation were also performed on diphenyl diselenide6.

R-Se-Se-R + TDAE + CF3I DMF R-Se-CF3
0 C to RT
-200%
RT overnight based of number of
1 eq. 2.2 eq 4.2 equivalents of diselenides


Scheme 1-15. Synthesis of trifluoromethyl selenoethers









Tablel-3. Synthesis of trifluoromethyl selenoethers
Entry R NMR Yield (%)*

1 phenyl 198

2 4-Chlorophenyl = 200

3 methyl 180
*based of number of equivalents of diselenides

The methodology is efficient for both aliphatic and aromatic diselenides.

The CF3I / TDAE methodology are very efficient for many electrophilic subtrates,

we are interested now to extend this methodology to longer perfluorinated chains by

using other perfluoroalkyl iodides. We would be able to access to a higher amount

biologically active compounds.













CHAPTER 2
SYNTHESIS OF PERFLUOROALKYL THIO AND SELENOETHERS

2.1 Introduction

Parallel to trifluorothioethers, trifluoroselenoethers, longer perfluoroalkyl chains are also

developed to be used as biologically active compounds. Few examples are given below.

Cl CF3 N112
SNH2

H3C ( N
S Cl
SCF2CF3 Br SCF2CF3

Figure 2-1. 2A28: insecticide Figure 2-2. 2B29: insecticide


SC4F9 CN


NN xNN

Cl Cl



CF3

Figure 2-3. 2C30: pesticide

Despite the increasing interest in perfluoroalkyl sulfides, few methods have been

developed to synthesize them. The two main methods consists in first through SRN1

reaction of aryl thiolates with perfloroalkyl iodide31 or bromide.32 The second method

involves perfluoroalkyl anion, generated from thermal decarboxylation of potassium









perfluoroalkyl carboxylate,33 with aryl disulfides with the inconvenience of possible

carbanion rearrangement or decomposition and one half of the disulfide is wasted.

Another notable method for synthesis of perfluoroalkyl selenides consists in reaction

between perfluoroalkyl radicals and diselenides.34 So far there is no efficient method for

synthesis of perfluoroalkyl aliphatic sulfides.


PhSH + C4F9I NaH p PhS-C4F9

66% 31

PhSK + CF3CF2Br PhS-CF2CF3

33% 32

PhS-SPh + CF3CF2CO2K A PhS-CF2CF3 + PhSK

70 %33

PhSe-SePh + 2 C4F9I HOCH a 2 PhSe-C4F9

57%34


Scheme 2-1. Different methods for synthesis of perfluoroalkyl sulfides and selenides

Our laboratories have developed a new and efficient method for synthesis of

trifluoromethyl sulfides and selenides, using CF3I / TDAE system.16 This methodology

has now been extended to longer perfluoroalkyl iodides.


R-S-S-R + TDAE + CF3I DMF 0 R-S-CF3
0 C to RT
180 200%
RT several hr 180200%
based of equivalents
1 eq. 2.2 eq 4.2 eq of disulfides

Scheme 2-2. Synthesis of trifluoromethyl sulfides with CF3I / TDAE methodology









2.2 Synthesis of Pentafluoroethyl Thioethers

The same way that TDAE reduces trifluoromethyl iodide into trifluoromethyl

anion, pentafluoroethyl iodide was also expected to be reduced by TDAE into

pentafluoroethyl anion. The tandem process, involving nucleophilic attack of

trifluoromethyl anion to disulfide followed by SRN1 by the resulting thiolate on the excess

of CF3I (Scheme 2-3), was also expected.


TDAE + CF3I CF3 + I + TDAE2

R-S-S-R + CF9 R-S-CF3 + R-S0

R-S + CF3I R-S-CF3 + I

Scheme 2-3. Tandem CF3I process in the synthesis of trifluoromethyl sulfides16

The first experiment was carried out using 1 equivalent of phenyl disulfide, 4.2

equivalents of C2F5I and 2.2 equivalents of TDAE added at -20 oC. The color of the

solution turned quickly deep red as TDAE was introduced. This may show the formation

of the complex between TDAE and C2F5I, like in the case between TDAE and CF3I. The

reaction mixture was allowed to warm up slowly. But unlike CF3I where the complex

with TDAE starts decomposing at 0 OC, the complex with C2F5I started decomposing

around -10 C, as white salt could be seen forming. Apparently the complex between

C2F5I and TDAE is less stable than that with CF3I. But the fact that TDAE was able to

form a complex with C2F5I was a good sign meaning that the reaction may proceed in the

same way as with CF3I / TDAE. The mixture was stirred overnight. 19F NMR was taken

to calculate the yield. The reaction yielded 198 % based on the number of equivalents of

disulfides (Table 2-1, entry 1).









R-S-S-R + TDAE + CF3CF2I DMF R-S-CF2CF3
-10 oC to RT
RT several hr
1 eq. 2.2 eq 4.2 eq

Scheme 2-4. Pentafluoroethylation of disulfides

Reactions with different disulfides (aromatic and aliphatic) were then performed.

The results are shown in Table 2-1.

Table 2-1. Synthesis of pentafluoroethyl thioethers
Entry R time at RT (hrs) NMR yield*

1 Phenyl32 12 >198

2 phenyl 2 >198

3 ethyl 2 135

4 ethyl 4 170

5 ethyl 12 175

6 butyl 12 180

7 2-pyridyl35 2 >198

8 4-pyridyl 2 190
*Based on the number of equivalents of disulfides

The entries 2, 7 and 8 proved that, as in the case of CF3I, 2 hours are sufficient to

obtain quantitative yield for aryl disulfides. But in entries 3 to 5, two, even four hours

didn't seem to be sufficient to obtain good yields in the case of aliphatic disulfides. The

mixture required to stirring overnight to be able to obtain 175 %. Even though, the yields

are very similar to the ones with CF3I, aliphatic disulfides require a much longer time.

This may be explained by the fact that it is more diificult for aliphatic thiolates to

undergo SRN1 reaction. Somehow the presence of TDAE seems to enhance the reactivity









of aliphatic thiolates on SRN1 reaction, since we could always obtain good yields from

aliphatic disulfides with CF3I / TDAE system. In the case of C2FI5 the complex formed

with TDAE is less stable than with CF3I and this may one of the reasons why the reaction

is slower for aliphatic disulfides. It may also come from the fact that C2FsI is less reactive

as a substrate in the SRN1 process.

In spite of longer reaction time for aliphatic disulfides, the yields obtained are

similar to the ones from CF3I. The two halves of the disulfides are used efficiently to

form two molecules of pentafluorethyl thioethers.

2.3 Synthesis of Pentafluoroethyl Selenoethers

Since diselenides have similar reactivities as disulfides. The reactions of

nucleophilic pentafluoroethylation were also performed on diselenides.


R-Se-Se-R + TDAE + CF3CF21 DMF R-Se-CF2CF3
-10 oC to RT
RT overnight
1 eq. 2.2 eq

Scheme 2-5. Pentafluoroethylation of diselenides

Table 2-2. Synthesis of pentafluoroethyl selenoethers
Entry R Eq. of C2F5I NMR yield* (%)

1 Phenyl34 2.2 100

2 phenyl 4.2 z 200

3 4-chlorophenyl 4.2 z 200
*Based on the number of equivalents of diselenides

As expected, from 1 equivalent of diselenides, 2.2 equivalents of C2FI5 gave

quantitatively 1 equivalent of pentafluoroethyl selenides (Table 2-2, entry 1) and 4.2

equivalents provided efficiently 2 equivalents of selenides.









2.4 Synthesis of Perfluorobutyl Thioethers

Since the nucleophilic perfluoroalkylation using TDAE was successfully extended

to C2F5I, longer perfluoroalkyl iodides were then considered for experiments, we decided

to performed reactions with nonafluorobutyl iodided


R-S-S-R + TDAE + C4F9I DMF R-S-C4F9
-20 oC to RT
RT overnight
1 eq. 2.2 eq

Scheme 2-6. Synthesis of perfluorobutyl thioethers

The reactions were performed in the same fashion as the usual reactions of

trifluoromethylation of disulfides, with the difference that C4F9I is a liquid instead of a

gas like CF3I or C2F5I, the total reflux condenser was not needed any longer. The

complex C4F9I / TDAE seems to be much less unstable than the ones from CF3I / TDAE,

since the usual TDAE salt was formed just above -20 C, very shortly after the addition of

TDAE.

Table 2-3. Synthesis of perfluorobutyl thioethers
Entry R Eq. of C4F91 NMR yield* (%)

1 Phenyl36 2.2 70

2 ethyl 2.2 40

3 butyl 2.2 40

4 2-pyridyl37 2.2 -100

5 4-pyridyl 2.2 z200

6 phenyl 4.4 140

7 butyl 4.4 40

8 2-pyridyl 4.4 195
*Based on the number of equivalents of disulfides









Aryl disulfides gave satisfactory to good yields (Table 2-3, entries 1 and 4) when

2.2 equivalents of C4F91 were used. But aliphatic disulfides resulted in only modest

yields, 40%, (Table 2-3, entries 2 and 3). This may be explained by the low stability of

the C4F9I / TDAE complex or the low reactivity of C4F9 anion towards aliphatic

disulfides. The case of 4-pyridyl disulfide (Table 2-3, entry 5) proved to be very

interesting. With only 2.2 equivalents of C4F9I, we were able to obtain 2 equivalents of

perfluorobutyl 4-pyridyl sulfide, where usually 4.2 equivalents were needed to obtain the

same results in other cases. This means that the tandem process16 (where the

perfluoroalkyl anion, formed by reduction of perfluoroalkyl iodide by TDAE, attacks

disulfide to form the first thioether and then the resulting thiolate reacts with the excess

of perfluoroalkyl iodide through SRN1 reaction to form the second thioether (Scheme 2-

3)) is not applicable anymore in this case. TDAE didn't reduce C4F9I into C4F9 anion but

instead reduced entirely 4-pyridyl disulfide, forming 2 equivalents of thiolate which react

with C4F9I through SRN1 mechanism. It seems that C4F9I is not as reactive towards TDAE

as CF3I or C2FsI and since the disulfide was also present in the reaction mixture when

TDAE was added and aryl disulfides can be easily reduced, TDAE preferably reduced 4-

pyridyl disulfide over C4F9I. This problem was not encountered in the case of CF3I and

C2FsI because their reactivity towards TDAE was high enough that TDAE reduced them

first.

When 4.4 equivalents of C4F91 were used on phenyl or 2-pyridyl disulfide, 140 %

and 195 % ofthioethers were obtained respectively (Table 2-3, entries 6 and 8). But 40 %

yield was only obtained for butyl disulfide, the same yield as when 2.2 equivalents of









C4F9I were used. It seems that aliphatic thiolates anions couldn't undergo reaction at all

through an SRN1 reaction with C4F91.

2.5 Synthesis of Perfluorobutyl Selenoethers

The syntheses of perfluorobutyl selenides were also performed.

R-S-S-R + TDAE + C4F9I DMF R-S-C4F9
-20 oC to RT
RT overnight
1 eq. 2.2 eq

Scheme 2-7. Synthesis of perfluorobutyl selenides

Table 2-4. Synthesis of )erfluorobutyl selenides
Entry R Eq. of C4F91 NMR yield* (%)

1 Phenyl34 2.2 z 200

2 methyl 2.2 z 200
*Based on the number of equivalents of diselenides

As with 4-pyridyl disulfide, both aryl and aliphatic diselenides only underwent

through SRN1 process, resulting in nearly 200 % yields when 2.2 equivalents of C4F91

were used (Table 2-4). Contrary to disulfides, aliphatic deselenides could react

quatitatively with C4F9I via SRN1 process.

2.6 Conclusion

The nucleophilic perfluoroalkylation methodology developed with CF3I / TDAE

system was successfully extended to C2F5I: similar results were obtained and the two

halves of disulfides and deselenides were efficiently used. The methodology seemed to

reach its limits with C4F9I. Whereas some aryl disulfides still gave good yields, aliphatic

disulfides resulted in poor yields. But the most important point is the fact that for some

disulfides and for all the diselenides, TDAE was unable to react with C4F9I and









preferably reduced disulfides or diselenides instead, forcing the reactions to undergo

exclusively through SRN1 mechanism of thiolate anion. From a synthetic point of view,

this didn't present a problem. On the contrary, a smaller amount of TDAE and

perfluorobutyl iodide was used to give 200% yields. But in the mechanistic point of view,

the tandem process, where the perfluoroalkyl iodide switches roles from being a reactant

to being a substrate in one pot reaction, couldn't be applied anymore and the role of

TDAE was only to reduce the disulfides. Moreover reducing disulfides to form thiolates

seems to be much less convenient than deprotonating a more easily available thiols by a

base, as the usual methods for perfluoralkyl thioether synthesis via SRN1 reactions.

However this C4F9I / TDAE, even when TDAE served only as reductant of

disulfides, still presents an advantage to other methods where the yields were not higher

than 60 %31,34

2.7 Experimental

Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus

300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with

external tetramethylsilane (TMS, 6 = 0.00 ppm) as a reference. Fluorine (19F) and proton

(1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFC13, 6 =

0.00 ppm) as a reference for 19F NMR and TMS (6 = 0.00 ppm) for H NMR. Deuterated

chloroform (CDC13) was used as NMR solvent.

2.7.1 General Synthesis of Pentafluoroethyl Thio and Selenoethers : Synthesis of
Phenyl Pentafluoroethyl Sulfide

In 25 mL, 3-neck-round bottom flask, equipped with a dewar type condenser and

N2, diphenyl disulfide (0.8 g, 3.68 mmol) was disolved in 10 mL of anhydrous DMF. The

solution was cooled at -20 oC. Pentafluoroethyl iodide (3.8 g, 15.45 mmol) was then









introduced to the solution. TDAE (2 mL, 8.1 mmol) was added around -15 C. The

reaction mixture became quickly dark red. The reaction was allowed to warm up slowly

to room temperature. And as the bath temperature reached -10 C white solid was formed.

The reaction mixture was stirred at room temperature for 2 hours (or overnight in the case

of alkyl disulfides). The orange solution was filtered and the solid was washed with

diethyl ether. The orange solution was filtered and the solid was washed with diethyl

ether (20 mL). 20 mL of water was added to the ether solution. The two phases were

separated and the aqueous phase was extracted with 20 mL of ether 2 more times. The

combined ether layers were washed with brine and dried over MgSO4. The solvent was

removed and the crude product was purified by silica gel chromatography (CH2C2 /

hexanes = 1:9) to give phenyl pentafluoroethyl sulfide in the yield of 198%

19F NMR(300 MHz, CDC13) 6 -83.00 (t, JFF = 3.1 Hz, 3F, CF3); -92.32 (q, JFF = 3.1

Hz ,2F, CF2) ppm

Ethyl Pentafluoroethyl Sulfide

1H NMR(300 MHz, CDC13) 6 2.70 (q, J = 7.2 Hz, 2H, CH2); 1.32 (t, J = 7.2 Hz,

3H, CH3)

19F NMR(300 MHz, CDC13) 6 -83.00 (t, JFF = 3.2 Hz ,3F, CF3); -92.32 (q, JFF = 3.2

Hz, 2F, CF2) ppm

Butyl Pentafluoroethyl Sulfide

H NMR(300 MHz, CDC13) 6 2.69 (t, J = 7.3 Hz, 2H, CH2); 1.66 (quintet, J = 7.6

Hz, 2H, CH2); 1.42 (sextuplet, J = 7.6 Hz, 2H, CH2); 0.93 (t, J = 7.3 Hz, 3H, CH3)

19F NMR(300 MHz, CDC13) 6 -82.95 (t, JFF = 3.2 Hz ,3F, CF3); -92.55 (q, JFF = 3.2

Hz, 2F, CF2) ppm









2-Pyridyl Pentafluoroethyl Sulfide35

1H NMR(300 MHz, CDC13) 6 8.47 (m, 1H, ArH); 7.62 (m, 2H, ArH); 7.11 (m, 1H,

ArH)

19F NMR(300 MHz, CDC13) 6 -83.17 (t, JFF = 2.01 Hz ,3F, CF3); -91.03 (q, JFF

2.01 Hz ,2F, CF2) ppm

4-Pyridyl Pentafluoroethyl Sulfide

1H NMR(300 MHz, CDC13) 6 8.51 (dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 2H, ArH); 7.37

(dd, Ji = 4.7 Hz, J2 = 1.75 Hz, 2H, ArH)

19F NMR(300 MHz, CDC13) 6 -82.95 (t, JFF = 2.14 Hz, 3F, CF3); -90.78 (q, JFF

2.14 Hz, 2F, CF2) ppm

Phenyl Pentafluoroethyl Selenide34

19F NMR(300 MHz, CDC13) 6 -84.74 (t, JFF = 3.2 Hz, 3F); -92.14 (q, JFF = 3.2 Hz,

2F, CF2) ppm

2.7.2 General Synthesis of Nonafluorobutyl Thio and Selenoethers : Synthesis of
Phenyl Nonafluorobutyl Sulfide

In a 25 mL round bottom flask, equipped with a rubber septum and N2, diphenyl

disulfide (0.8 g, 3.68 mmol) was disolved in 10 mL of anhydrous DMF. The solution was

cooled at -30 oC. Nonafluorobutyl iodide (1.4 mL, 15.45 mmol) was then introduced to

the solution. TDAE (2 mL, 8.1 mmol) was added around -20 C. The reaction mixture

became quickly dark red. White solid was formed shortly after the addition of TDAE.

The mixture was allowed to warm up slowly to the room temperature was stirred

overnight. The orange solution was filtered and the solid was washed with diethyl ether

(20 mL). 20 mL of water was added to the ether solution. The two phases were separated

and the aqueous phase was extracted with 20 mL of ether 2 more times. The combined









ether layers were washed with brine and dried over MgSO4. The solvent was removed

under vacum and the crude product was purified by silica gel chromatography (CH2C2 /

hexanes = 1:9) to give phenyl nonafluorobutyl sulfide in the yield of 140%

19F NMR(300 MHz, CDC13) 6 -81.28 (t, JFF = 10.2 Hz, 3F, CF3); -87.43 (m, 2F,

SCF2); -120.46 (m, 2F, CF2); -125.90 (m, 2F, CF2) ppm

Ethyl Nonafluorobutyl Sulfide

1H NMR(300 MHz, CDC13) 6 2.70 (q, J = 7.2 Hz, 2H, CH2); 1.32 (t, J = 7.2 Hz,

3H, CH3)

19F NMR(300 MHz, CDC13) 6 -81.30 (t, JFF = 8.9 Hz, 3F, CF3); -87.80 (m, 2F,

SCF2); -121.05 (m, 2F, CF2); -125.60 (m, 2F, CF2) ppm

Butyl Nonafluorobutyl Sulfide

H NMR(300 MHz, CDC13) 6 2.69 (t, J = 7.3 Hz, 2H, CH2); 1.66 (quintet, J = 7.6

Hz, 2H, CH2); 1.42 (sextuplet, J = 7.6 Hz, 2H, CH2); 0.93 (t, J = 7.3 Hz, 3H, CH3)

19F NMR(300 MHz, CDC13) 6 -81.35 (t, JFF = 8.5 Hz, 3F, CF3); -87.68 (m, 2F,

SCF2); -120.97 (m, 2F, CF2); -125.48 (m, 2F, CF2) ppm

2-Pyridyl Nonafluorobutyl Sulfide37

1H NMR(300 MHz, CDC13) 6 8.47 (m, 1H, ArH); 7.62 (m, 2H, ArH); 7.11 (m, 1H,

ArH)

19F NMR(300 MHz, CDC13)6 -81.13 (t, JFF = 10.7 Hz, 3F, CF3); -86.13 (m, 2F,

SCF2); -120.35 (m, 2F, CF2); -125.70 (m, 2F, CF2) ppm

4-Pyridyl Nonafluorobutyl Sulfide

1H NMR(300 MHz, CDC13) 6 8.51 (dd, J1 = 4.8 Hz, J2 = 2.0 Hz, 2H, ArH); 7.37

(dd, Ji = 4.7 Hz, J2 = 1.75 Hz, 2H, ArH)






24

19F NMR(300 MHz, CDC13) 6 -81.20 (t, JFF = 10.5 Hz, 3F, CF3); -86.00 (m, 2F,

SCF2); -120.25 (m, 2F, CF2); -125.60 (m, 2F, CF2) ppm

Phenyl Nonafluorobutyl Selenide34

19F NMR(300 MHz, CDC13) 6 -81.47 (t, JFF = 10.7 Hz, 3F, CF3); -87.34 (m, 2F,

SCF2); -119.14 (m, 2F, CF2); -126.05 (m, 2F, CF2) ppm














CHAPTER 3
PERFLUOROALKYLATION OF IMINE TOSYLATES

3.1 Introduction

Our laboratories have developed methodologies for nucleophilic

trifluoromethylation of numerous substrates, such as aldehydes12, cyclic sulfates5,

benzoyl chlorides13 or disulfides16, using CF3I / TDAE system. Trifluoromethylamines

are very interesting compounds because they can serve as synthetic intermediates to

biologically active molecules, as shown in Figures 3-1 and 3-2, where 3A can be used as

pesticide38 and 3B as pain-reliever39

F3C NH

S CF3 I I
I N, I N Z


S H

Figure 3-1. 3A Figure 3-2. 3B

Previously trifluoromethylamines were only synthesized from precursors (i.e.

ketones) already containing trifluoromethyl group.40-48 Prakash and coworkers have used

Ruppert's reagent (CF3TMS) with imine derivatives to prepare trifluoromethylamines49

and, in particular, chiral trifluoromethylamines.50'51 Indeed, the use of CF3TMS proved to

be very effective for nucleophilic trifluoromethylation of N-tosyl aldimines and N-(2-

methyl-2- propane-sulfinyl)imines (Scheme 3-1), with the latter reactions exhibiting

excellent diastereoselectivity.









Simple alkyl- or aryl-substituted imines are relatively unreactive toward

nucleophilic trifluoromethylation, although Blazejewski and co-workers were able to

obtain modest to good yields for aryl systems by facilitating the reaction of CF3TMS

using TMS-imidazole.52 As Prakash showed, the reactivity of imines toward nucleophilic

trifluoromethylation can be significantly enhanced by using N-tosylimines, with thep-

toluenesulfonyl group being removed from the adduct by its treatment with phenol and

48% HBr to give the respective primary amine products.49

F3C
TBAT
__N-Ts + CF3TMS TBAT N Ts
Ph THF, 0 5 C / H
Ph Ph
90%


O F3C O
-N-S + CF3TMS a N-S
Ph tBu Ph tBu
P \tBu THF, -55 C Ph/ \ \
80%
d.r > 97%

Scheme 3-1. Trifluoromethylation of imines using Ruppert's reagent

Using the same CF3I / TDAE methodology than developed for trifluoromethylation

of aldehydes12, similar results53 to Prakash's methods could be obtained (Scheme 3-2).

Unfortunately, the analogous reactions with imines bearing aliphatic substituents on the

imine carbon did not produce the desired adducts. Such attempts included the N-

tosylimines of acetophenone, p-chloroacetophenone, cyclohexanone, and hexanal. In

contrast, aliphatic aldehydes had been reported to provide adducts using Prakash's

CF3TMS methodology.49









F3C
Ts CF3I / TDAE (2.2 equiv.) N Ts

Ar DMF, -30 0 C H
Ar Ar
62 86%



0 F3C. 0
N- S CF3I / TDAE (2.2 equiv.) N

Ph Tol DMF, -30-0 C Ph Tol
66%
d.r = 87:13

Scheme 3-2. Trifluoromethylation of imines using CF3I / TDAE

Parallel to trifluoromethylamines, higher perfluoroalkylamines gather also much

interest from pharmaceutical and agrochemical industries. For example, 3C can be used

as a treatment against osteoporosis54 and 3D as a treatment of Alzheimer's disease5





OCH3 N-/


NHN
0 H 0

NC A N
NC H tBu CF2CF3 H CF2CF3


Figure 3-3. 3C Figure 3-4. 3D

Since in Chapter 2, we have shown that the CF3I / TDAE methodology could be extend

to longer perfluoroalkyl iodides, such as pentafluoroethyl iodide or nonafluorobutyl

iodide, we decided then to try to synthesize other perfluoroalkyl amines










3.2 Synthesis of Tosyl Imines


R1 R1
O_ + H2N T __T BF3.OEt2 or Ts-OH _=
O + H2N Ts N--Ts
toluene, reflux
R2 R2

Scheme 3-1. Synthesis oftosyl imines

The imines were easily prepared from aromatic aldehydes and tosyl amine, as shown in

Table 3-1. Unfortunately because of the electron withdrawing character of the tosyl

group, tosyl amine was not reactive towards ketones or alphatic aldehydes (entries 3.14-

3.16)

Table 3-1 Syvnthesis oftosvl imines


entry R1 R2 Yield (%)


3.1 H 80




3.2 H 85
Me"



3.3 H 85
Cl



3.4 H 88
F



3.5 H 80
F3C


. .. .











3.6 / H 30




3.7 / H 65
0




3.8 H 95
^-~N
CH3


3.9 CH3 0




3.10 CF3 0




3.11 C7H15 H 0


3.3 Pentafluoroethylation of Tosyl Imines


Ar

A=rN-Ts + CF3CF2I

H


+ TDAE DMF
-20 OC to RT


Scheme 3-2. Nucleophilic pentafluoroethylation of tosyl imines









Table 3-2. Nucleophilic pentafluoroethylation of tosyl imines
Yield with
Entry Ar Yield (%) CF3153 (



3.1a 50 86




3.2a 70 84
Me"



3.3a 70 78
Cl



3.4a 72 81
F



3.5a 6 68
F3C



3.6a ( 55
S



3.7a 60





3.8a 0 -
CHN
_________CH3 __________ ______









In general, the reactions provided similar results than with CF3I / TDAE system,

with slightly lower yields. For the case of 1-methylindol-3-imine tosylate (entry 3.10a)

the absence of reactivity may be explained by one of the resonance forms shown in

Figure 3-1: with the carbon being on the position 3, the indole group becomes a good

electron donating group, reducing hugely the electrophilic character of the carbon on the

imine, thus the lack of reactivity towards C2F5 nucleophile.

Ts Ts



0 NN

\ "N



Figure 3-5. A resonance form of N-(N-methyl-3-indolylmethylene)-p-
methylbenzenesulfonamide

3.4 Perfluorobutylation of Tosyl Imines

Since good yields could be obtained with C2FsI, experiments with C4F91 were performed

to extend further the methodology


Ar C4F9

N-Ts + C4F91 + TDAE DMF Ar N-

H -20 OC to RT

1 2.2 2.2


Scheme 3-3. Nucleophilic perfluorobutylation oftosyl imines

In general the yields are lower than with C2FsI, but when the aryl group contains

electron withdrawing elements, the yields are good and comparable to the ones from

C2FsI (Table 3-3, entries 3.3b 3.5b). Furyl and thiophenyl tosyl imines are not very









reactive but the yields are decent. Like as C2FsI, 1-methyl 3-indolyl tosyl imine is not

reactive at all toward perfluoroalkylation. (Table 3-3, entry 3.8b)

Table 3-3. Nucleophilic perfluorobutylation of tosyl imines

Entry Ar Yield (%)



3.2b 50
Me"



3.3b 70
ClI



3.4b 70
F


3.5b 75
F3C


3.6b / \ 45
S


3.7b / O 40




3.8b 0
^-~N
CH3

Surprisingly the system C4F9I / TDAE provided rather good yields. Unlike with

disulfides where C4F9I didn't seem to be reactive enough (Chapter 2), the system C4F9I /

TDAE provided sometimes yields similar to the ones from C2F5I / TDAE.









3.5 Conclusion

The nucleophilic trifluoromethylation methodology of tosyl imines using

trifluoromethyl iodide and TDAE could be extended successfully with pentafluoroethyl

iodide and nonafluorobutyl iodide. Different substrates were used and provided fair to

very good yields.

3.6 Experimental

Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus

300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with

external tetramethylsilane (TMS, 6 = 0.00 ppm) as a reference. Fluorine (19F) and proton

(1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFC13, 6 =

0.00 ppm) as a reference for 19F NMR and TMS (6 = 0.00 ppm) for H NMR. Deuterated

chloroform (CDC13) was used as NMR solvent.

3.6.1 Syntheses of Tosyl Imines

Synthesis ofN-(benzylidene)-p-methylbenzenesulfonamide (3.1)

In a 100 mL one-neck round bottom flask, 4-toluenesulfonamide (2.57g, 15 mmol)

and benzaldehyde (1.52 mL, 15mmol) was mixed in 40 mL of toluene. BF3-EtO2 (0.15

mL) was added under N2. The flask was equipped with a Dean-Stark apparatus. The

reaction mixture was refluxed for 14 hours, then cooled to room temperature and poured

into 2M NaOH (10mL). The organic phase was washed with brine and water until neutral

pH, dried over anhydrous magnesium sulfate and the solvent was removed by vacuum.

The oily residue was recrystallized from ethyl acetate to give a white solid; yield: 3.11 g

(80 %)









1HNMR (CDC13) 6 9.03 (s, 1H, CH=N-Ts); 7.91 (m, 4H, ArH); 7.62 (m, 1H,

ArH); 7.48 (m, 2H, ArH); 7.34 (m, 2H, ArH); 2.44 (s, 3H, CH3) ppm.

Synthesis of N-(4-methylbenzylidene)-p-methylbenzenesulfonamide (3.2)

The procedure and the workup are the same as the synthesis of N-(benzylidene)-p-

methylbenzenesulfonamide, using 4-methylbenzaldehyde toyield 85 % of white solid

1H NMR (CDC13) 6 8.99 (s, 1H, CH=N-Ts); 7.88 (d, J = 8.1 Hz, 2H, ArH); 7.82 (d,

J = 8.1 Hz, 2H, ArH); 7.34 (d, J = 8.1 Hz, 2H, ArH); 7.29 (d, J = 8.1 2H, ArH); 2.43 (s,

6H, CH3) ppm.

Synthesis of N-(4-chlorobenzylidene)-p-methylbenzenesulfonamide (3.3)

In a 100 mL one-neck round bottom flask, 4-toluenesulfonamide (2.57g, 15 mmol)

and 4-chlorobenzaldehyde (2.10g, 15mmol) was mixed in 40 mL of toluene. BF3-EtO2

(0.15 mL) was added under N2. The flask was equipped with a Dean-Stark apparatus. The

reaction mixture was refluxed for 14 hours, and then cooled to room temperature. White

crystals precipitated upon cooling. The solid was filtered, then washed with water and

dried under vacuum. Yield = 2.74 g (85 %)

H NMR (CDC13) 6 8.99 (s, 1H); 7.89 (d, J = 6.3 Hz, 2H); 7.86 (d, J = 6.3 Hz, 2H);

7.47 (d, J = 8.4 Hz, 2H); 7.35 (d, J = 8.4 Hz, 2H); 2.44 (s, 3H) ppm.

Synthesis of N-(4-fluorobenzylidene)-p-methylbenzenesulfonamide (3.4)

The procedure and the workup are the same as the synthesis of N-(benzylidene)-p-

methylbenzenesulfonamide, using 4-fluorobenzaldehyde to yield 88% of white solid.

H NMR (CDC13) 6 9.00 (s, 1H, CH=N-Ts); 7.96 (m, 2H, ArH); 7.89 (d, J = 8.4

Hz, 2H, ArH); 7.35 (d, J = 8.7 Hz, 2H, ArH); 7.19 (m, 2H, ArH); 2.44 (s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -101.59 (t, J = 8.7 Hz, 1F) ppm.









Synthesis of N-(4-trifluoromethylbenzylidene)-p-methylbenzenesulfonamide (3.5)

Following the above procedure for 3.3, by using 4-trifluoromethylbenzaldehyde

(2mL, 15mmol), provided 3.92 g (80% yield) of white solid.

1H NMR (CDC13) 6 9.08 (s, 1H, CH=N-Ts); 8.04 (d, J = 8.1 Hz, 2H, ArH); 7.90 (d,

J = 8.4 Hz, 2H, ArH); 7.75 (d, J = 8.1 Hz, 2H, ArH); 7.34 (d, J = 8.4 Hz, 2H, ArH); 2.45

(s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -63.83 (s, 3F, CF3) ppm.

Synthesis of N-(2-thiophenylmethylene)-p-methylbenzenesulfonamide (3.6)

In a 100 mL one-neck round bottom flask, 4-toluenesulfonamide (2.57g, 15 mmol)

and 2-thiophenecarboxaldehyde (1.4 mL, 15mmol) was mixed in 40 mL of toluene. A

catalytic amount of p-toluenesulfonic acid monohydrate was added. The flask was

equipped with a Dean-Stark apparatus. The reaction mixture was refluxed for 14 hours.

The solution turned quickly dark green and black tar was formed. After 14 hours,

charcoal was added to the hot solution and the mixture was stirred at 100 oC for 1 hour

and filtered while it was still hot. The solvent was removed under vacuum.

Recrystallization from benzene gave 1.07g (30%) of N-(2-thiophenylmethylene)-p-

methylbenzenesulfonamide as a silvery gray solid

1H NMR (CDC13) 6 9.11 (s, 1H, CH=N-Ts); 7.87 (d, J = 8.7 Hz, 2H, ArH); 7.77 (d,

J = 4.2 Hz, 2H, ArH); 7.34 (d, J = 8.7 Hz, 2H, ArH); 7.21 (m, 1H, ArH); 2.44 (s, 3H,

CH3) ppm.









Synthesis of N-(2-furanylmethylene)-p-methylbenzenesulfonamide (3.7)

The same procedure and workup as for N-(2-thiophenylmethylene)-p-

methylbenzenesulfonamide, using 2-furfural (1.24mL, 15 mmol), gave 2.43 g (65%) of

light brown solid.

1HNMR (CDC13) 6 8.81 (s, 1H, CH=N-Ts); 7.87 (d, J = 8.4 Hz, 2H, ArH); 7.74

(m, H, ArH); 7.34 (m, 3H, ArH); 6.64 (dd, J = 5.1 and 3.3 Hz, 1H, ArH); 2.43 (s, 3H,

CH3) ppm.

Synthesis of N-(N-methyl-3-indolylmethylene)-p-methylbenzenesulfonamide (3.8)

In a 100 mL one-neck round bottom flask, 4-toluenesulfonamide (2.57g, 15 mmol)

and N-methyl-3-indolcarbaxaldehyde (2.39 g, 15mmol) was mixed in 40 mL of toluene.

A catalytic amount of p-toluenesulfonic acid monohydrate was added. The flask was

equipped with a Dean-Stark apparatus. The reaction mixture was refluxed for 14 hours.

The solution became rapidly deep purple. After reflux, the reaction mixture was cooled to

room temperature and the solvent was removed in vacuo. The crude solid was

recrystallized in benzene to give 4.27 g (95% yield) of N-(N-methyl-3-indolylmethylene)-

p-methylbenzenesulfonamide as a purple solid.

1H NMR (CDC13) 6 9.09 (s, 1H, CH=N-Ts); 8.30 (d, J = 6.9 Hz, 1H, ArH); 7.89 (d,

J = 8.1 Hz, 2H, ArH); 7.74 (s, 1H, ArH); 7.33 (3, 5H, ArH); 3.88 (s, 3H, N-CH3); 2.40 (s,

3H, CH3) ppm.

3.6.2 General Procedure for Pentafluoroethylation of Tosyl Imines : Synthesis of
Methyl-N-(3,3,3,2,2-pentafluoro-1-phenyl-propyl)-benzenesulfonamide (3.1a)

In 25 mL, 3-neck-round bottom flask, equipped with a total reflux condenser and

N2, N-(benzylidene)-p-methylbenzenesulfonamide (0.259 g, 1 mmol) was disolved in 6

mL of anhydrous DMF. The solution was cooled at -30 oC. Pentafluoroethyl iodide (0.6









g, 2.4 mmol) was then introduced to the solution. TDAE (0.51 mL, 2.2 mmol) was added

around -20 C. The reaction mixture became quickly orange red. The reaction was

allowed to warm up slowly to room temperature. And as the bath temperature reached -

10 C white solid was formed. The reaction mixture was stirred at room temperature

overnight. About 15 mL of 10% H2S04 aqueous solution was added slowly to quench the

reaction. As the acid solution was added, the reaction mixture first became clear as the

TDAE salt was dissolved in water. But the mixture became cloudy again as the product

precipitated out. The solution was stirred for a while as more and more product

precipitated. The solid was collected via filtration and dissolved in 30 mL of ether. The

ether solution was washed 3 times with water to eliminate remaining DMF. The ether

phase was dried over anhydrous MgSO4 and the solvent was removed by vacuum. The

pale yellow crude product was recrystallized in toluene to afford 0.189 g of a white solid.

(50%)

1HNMR (CDC13) 6; 7.52 (d, J = 8.4 Hz, 2H, ArH); 7.24 (m, 3H, ArH); 7.10 (m,

4H, ArH); 5.48 (d, J = 9.9 Hz, 1H, NH); 4.97 (m, 1H, CH-N); 2.33 (s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -81.42 (s, 3F, CF2-CF3); -120.67 (dd, J1 = 291.9 Hz, J2 = 12.9

Hz, 1F, CF-CF3); -122.86 (dd, Ji = 291.6 Hz, J2 = 12.6 Hz, 1F, CF-CF3) ppm.

Anal. Calcd for C16H14F8NO2S: C, 50.670; H, 2.694; N, 3.694. Found: C, 50.390;

H, 3.591; N, 3.590.









4-Methyl-N- [3,3,3,2,2-pentafluoro-(4-methyl-phenyl)-propyl]-benzenesulfonamide

(3.2a) White solid (70 % yield)

1H NMR (CDC13) 6; 7.52 (d, J = 8.1 Hz, 2H, ArH); 7.09 (d, J = 8.1 Hz, 2H, ArH);

7.02 (d, J = 8.4 Hz, 2H, ArH); 6.98 (d, J = 8.7 Hz, 2H, ArH); 5.50 (d, J = 9.9 Hz, 1H,

NH); 4.92 (m, 1H, CH-N); 2.34 (s, 3H, CH3); 2.29 (m, 3H, CH3) ppm.

19F NMR (CDC13) 6 -81.42 (s, 3H, CF2-CF3); -120.72 (dd, J1 = 291.6 Hz, J2 = 12.6

Hz, IF, CF-CF3); -122.78 (dd, Ji = 291.6 Hz, J2 = 12.6 Hz, IF, CF-CF3) ppm.

Anal. Calcd for C17H16F5NO2S: C, 51.908; H, 4.071; N, 3.562. Found: C, 51.716;

H, 4.015; N, 3.503.

4-Methyl-N-[3,3,3,2,2-pentafluoro-(4-chloro-phenyl)-propyl]-benzenesulfonamide

(3.3a) White solid (70 % yield)

1HNMR (CDC13) 6; 7.51 (d, J = 8.4 Hz, 2H, ArH); 7.21 (d, J = 8.4 Hz, 2H, ArH);

7.13 (d, J = 8.4 Hz, 2H, ArH); 7.05 (d, J = 8.4 Hz, 2H, ArH); 5.24 (d, J = 9.3 Hz, 1H,

NH); 4.98 (m, 1H, CH-N); 2.38 (s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -81.39 (s, 3H, CF2-CF3); -120.35 (dd, J1 = 293.7 Hz, J2 = 13.5

Hz, 1F, CF-CF3); -123.33 (dd, Ji = 293.7 Hz, J2 = 13.5 Hz, 1F, CF-CF3) ppm.

Anal. Calcd for C16H13C1F5N02S: C, 46.398; H, 3.141; N, 3.383. Found: C, 46.255;

H, 3.122; N, 3.355.

4-Methyl-N- [3,3,3,2,2-pentafluoro-(4-fluoro-phenyl)-propyl] -benzenesulfonamide

(3.4a) White solid (72 % yield)

1H NMR (CDC13) 6; 7.52 (d, J = 8.4 Hz, 2H, ArH); 7.12 (m, 4H, ArH); 6.92 (t, J =

8.4 Hz, 2H, ArH); 5.37 (d, J = 9.3 Hz, 1H, NH); 4.98 (m, 1H, CH-N); 2.36 (s, 3H, CH3)


ppm.









19F NMR (CDC13) 6 -81.39 (s, 3H, CF2-CF3); -111.84 (m, IF, ArF) -120.60 (dd, J1

= 291.3 Hz, J2 = 11.1 Hz, IF, CF-CF3); -123.19 (dd, J1 = 293.7 Hz, J2 = 13.5 Hz, IF, CF-

CF3) ppm.

Anal. Calcd for C16H13F6NO2S: C, 48.363; H, 3.274; N, 3.526. Found: C, 48.259;

H, 3.266; N, 3.333

4-Methyl-N-[3,3,3,2,2-pentafluoro-(4-trifluoromethyl-phenyl)-propyl]-

benzenesulfonamide (3.5a) White solid (68 % yield)

1H NMR (CDC13) 6 7.47 (d, J = 6.1 Hz, 2H, ArH); 7.45 (d, J = 6.1 Hz, 2H, ArH);

7.23 (d, J = 8.1 Hz, 2H, ArH); 7.06 (d, J = 8.1 Hz, 2H, ArH); 5.65 (d, J = 9.9 Hz, 1H,

NH); 5.05 (m, 1H, CH-CF2); 2.31 (s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -63.54 (s, 3F, CF3); -81.41 (s, 3H, CF2-CF3); -119.54 (dd, J1 =

292.5 Hz, J2 = 14.4 Hz, IF, CF-CF3); -123.91 (dd, J1 = 292.5 Hz, J2 = 14.4 Hz, IF, CF-

CF3) ppm.

Anal. Calcd for C17H13F8NO2S: C, 45.638; H, 2.908; N, 3.132. Found: C, 45.340;

H, 2.833; N, 3.011.

4-Methyl-N- [3,3,3,2,2-pentafluoro-(2-thiophenyl)-propyl]-benzenesulfonamide (3.6a)

White solid (55 % yield)

1HNMR (CDC13) 6 7.58 (d, J = 8.4 Hz, 2H, ArH); 7.25 (m, 1H); 7.17 (d, J = 8.4

Hz, 2H, ArH); 6.88 (m, 2H); 5.34 (m, 1H, CH-N); 5.018 (m, 1H, NH) 2.38 (s, 3H, CH3)

ppm.

19F NMR (CDC13) 6 -82.29 (s, 3H, CF2-CF3); -120.71 (dd, J1 = 289.2 Hz, J2 11.1

Hz, IF, CF-CF3); -123.36 (dd, J1 = 289.2 Hz, J2 = 11.1 Hz, IF, CF-CF3) ppm.









Anal. Calcd for C14H12F5N02S2: C, 43.636; H, 3.117; N, 3.636. Found: C, 43.578;

H, 3.099; N, 3.620.

4-Methyl-N-[3,3,3,2,2-pentafluoro-(2-furanyl)-propyl]-benzenesulfonamide (3.7a)

Light brown solid (60 % yield)

1HNMR (CDC13) 6 7.60 (d, J = 8.4 Hz, 2H, ArH); 7.19 (m, 3H); 6.21 (m, 2H,

ring); 5.33 (d, J = 10.2 Hz, 1H, NH); 5.11 (m, 1H, CH-CF2); 2.38 (s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -82.02 (s, 3H, CF2-CF3); -120.72 (dd, J1 = 291.3 Hz, J2 = 13.2

Hz, 1F, CF-CF3); -122.33 (dd, J1 = 289.2 Hz, J2 = 13.1 Hz, 1F, CF-CF3) ppm.

Anal. Calcd for C14H12F5NO3S: C, 45.528; H, 3.252; N, 3.790. Found: C, 45.246;

H, 3.255; N, 3.747.

3.6.3 General Procedure for Perfluorobutylation of Tosyl Imines: Synthesis of 4-
Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(4-methyl-phenyl)-propyl]-
benzenesulfonamide (3.2b)

In a 25 mL round bottom flask, connected with N2, N-(4-methylbenzylidene)-p-

methylbenzenesulfonamide (0.273 g, 1 mmol) was disolved in 6 mL of anhydrous DMF.

The solution was cooled at -30 oC. Nonafluorobutyl iodide (0.38 mL, 2.2 mmol) was then

introduced to the solution. TDAE (0.51 mL, 2.2 mmol) was added around -20 C. The

reaction mixture became quickly orange red and white solid was formed shortly after the

addition of TDAE. The reaction was allowed to warm up slowly to room temperature.

The reaction mixture was stirred at room temperature overnight. About 15 mL of 10%

H2SO4 aqueous solution was added slowly to quench the reaction. As the acid solution

was added, the reaction mixture first became clear as the TDAE salt was dissolved in

water. But the mixture became cloudy again as dark brown oil could be seen forming.

The solution was stirred for several hours as more brown vicous oil was formed. 30 mL









of ether were added to dissolve the oil. The two phases were separated and the ether

solution was washed 3 times with water to eliminate remaining DMF. The ether phase

was dried over anhydrous MgSO4 and the solvent was removed by vacuum. The pale

yellow crude product was recrystallized in toluene to afford 0.189 g of a white solid.

(50%)

1HNMR (CDC13) 6; 7.51 (d, J = 8.4 Hz, 2H, ArH); 7.09 (d, J = 8.1 Hz, 2H, ArH);

7.00 (m, 4H, ArH); 5.33 (d, J = 9.9 Hz, 1H, NH); 5.04 (m, 1H, CH-N); 2.34 (s, 3H, CH3);

2.29 (s, 3H, CH3) ppm.

19F NMR (CDC13)6 -81.43 (t, J = 9.9, 3F, CF2-CF3); -116.98 (dm, J1 = 301.5 Hz,,

1F, CF-CH); -118.88 (dm, J1 = 301.5 Hz, 1F, CF-CH); -121.47 (m, 2F, CF2); 126.53 (m,

2F, CF2) ppm.

Anal. Calcd for C19H16F9NO2S: C, 46.212; H, 3.243; N, 2.837. Found: C, 46.239;

H, 3.185; N, 2.821

4-Methyl-N-[5,5,5,4,4,3,3,2,2-nonafluoro-(4-chloro-phenyl)-propyl]-

benzenesulfonamide (3.3b) White solid (70 % yield)

1HNMR (CDC13) 6; 7.50 (d, J = 8.4 Hz, 2H, ArH); 7.18 (d, J = 8.7 Hz, 2H, ArH);

7.11 (d, J = 7.8 Hz, 2H, ArH); 7.04 (d, J = 8.4 Hz, 2H, ArH) 5.60 (d, J = 9.9 Hz, 1H,

NH); 5.07 (m, 1H, CH-N); 2.37 (s, 3H, CH3) ppm.

19F NMR (CDC13)6 -81.41 (t, J = 11.1, 3F, CF2-CF3); -116.52 (dm, J1 = 304.8 Hz,

1F, CF-CH); -119.38 (d3, J = 304.8 Hz, 1F, CF-CH); -121.37 (m, 2F, CF2); 126.55 (m,

2F, CF2) ppm.

Anal. Calcd for C18H13C1F9NO2S: C, 42.038; H, 2.530; N, 2.724. Found: C, 41.904;

H, 2.457; N, 2.685.









4-Methyl-N- [5,5,5,4,4,3,3,2,2-nonafluoro-(4-trifloromethyl-phenyl)-propyl]-

benzenesulfonamide (3.5b) White solid (75 % yield)

1H NMR (CDC13) 6; 7.47 (d, J = 8.1 Hz, 2H, ArH); 7.42 (d, J = 8.4 Hz, 2H, ArH);

7.22 (d, J = 8.1 Hz, 2H, ArH); 7.04 (d, J = 8.4 Hz, 2H, ArH) 5.99 (d, J = 10.2 Hz, 1H,

NH); 5.16 (m, 1H, CH-N); 2.31 (s, 3H, CH3) ppm.

19F NMR (CDC13)6 -63.57 (s, 3F, Ar-CF3); -81.41 (t, J = 11.1 Hz, 3F, CF2-CF3); -

115.84 (dm, J = 304.5 Hz, IF, CF-CH); -119.77 (dm, J = 304.5 Hz, IF, CF-CH); -121.33

(m, 2F, CF2); 126.52 (m, 2F, CF2) ppm.

Anal. Calcd for C19H13F12N02S: C, 41.654; H, 2.375; N, 2.558. Found: C, 41.751;

H, 2.297; N, 2.553

4-Methyl-N- [5,5,5,4,4,3,3,2,2-nonafluoro-(2-thiophenyl -phenyl)-propyl]-

benzenesulfonamide (3.6b) White solid (45 % yield)

1H NMR (CDC13) 6; 7.57 (d, J = 8.1 Hz, 2H, ArH); 7.23 (m, 1H, ring); 7.14 (d, J =

8.1 Hz, 2H, ArH); 6.90 (m, 1H, ring); 6.83 (m, 1H, ring); 5.42 (m, 2H, CH-N and NH);

2.36 (s, 3H, CH3) ppm.

19F NMR (CDC13) 6 -81.39 (t, J = 11.1 Hz, 3F, CF2-CF3); -116.69 (dm, J = 297.9

Hz, 1F, CF-CH); -119.22 (dm, J = 297.9 Hz, 1F, CF-CH); -121.47 (m, 2F, CF2); 126.52

(m, 2F, CF2) ppm.

Anal. Calcd for C16H12F9NO2S2: C, 39.555; H, 2.472; N, 2.884. Found: C, 39.567;

H, 2.421; N, 2.778









4-Methyl-N- [5,5,5,4,4,3,3,2,2-nonafluoro-(2-furanyl-phenyl)-propyl]-

benzenesulfonamide (3.7b) Brown solid (40 % yield)

1HNMR (CDC13) 6; 7.59 (d, J = 8.4 Hz, 2H, ArH); 7.26 (m, 1H, ring); 7.19 (d, J =

8.4 Hz, 2H, ArH); 6.21 (m, 2H, ring); 5.42 (m, 2H, CH-N and NH); 2.38 (s, 3H, CH3)

ppm.

19F NMR (CDC13) 6 -81.40 (t, J = 11.1 Hz, 3F, CF2-CF3); -116.69 (dm, J = 297.9

Hz, 1F, CF-CH); -119.22 (dm, J = 297.9 Hz, 1F, CF-CH); -121.47 (m, 2F, CF2); 126.52

(m, 2F, CF2) ppm.

Anal. Calcd for C16H12F9NO3S: C, 40.908; H, 2.557; N, 2.983. Found: C, 40.733;

H, 2.446; N, 2.907
















CHAPTER 4
PERFLUOROAKYLATION OF ALDEHYDES AND KETONES

4.1 Introduction

Along with a-trifluoromethyl alcohols, longer a-perfluoroalkyl alcohols are

generating growing interests from industries, as one can notice the fast increase of the

number of patented molecules containing a-perfluoroalkyl alcohol function in the past

few years. These molecules can be used as fungicide56 (Figure 4-1) or insecticide.57


o



OH F
F3 C- CF 2

Figure 4-1. 4A56 : Fungicide

Cl CF 3

NC \ I


Cl
F3C- (CF2) 3-CH NH2

OH

Figure 4-2. 4B57 : insecticide

Our laboratories have developed successfully nucleophilic trifluoromethylation of

aldehydes and ketones by using CF3I / TDAE system12. Since the methodology could be

extended for pentafluoroethyl iodide and nonafluorobutyl iodide for disulfides (Chapter

2) and tosyl imines (Chapter 3), the research was then performed on aldehydes and

ketones.









4.2 Pentafluoroethylation of Aldehydes and Ketones

The procedure for the pentafluoroethylation of aldehydes and ketones is very

similar than the trifluoromethylation of aldehydes12. Since earlier studies on the C2F5I /

TDAE system have shown that the resulting complex is stable below -10 C (Chapter 2),

the reaction could be performed at -15 or -10 OC.

O OH
11 + CF3CF2I + TDAE DMF Ri R2
R, R2 -15 oC to RT
CF2CF3
hv, 1 hr
1 eq 2.2 eq 2.2 eq RT, 12 hrs

Scheme 4-1. Pentafluoroethylation of aldehydes and ketones

By comparison to the yields obtained in trifluoromethylation, the products from

pentafluoroethylation were obtained in very similar yields. The yields are generally lower

except for fluorenone (entry 4.5) where the yield was 95 % compared to 73 % for

trifluoromethylated product. The aromatic aldehydes provided high yields (entries 4.1-

4.3). The yields from ketones products are decent, but this may be explained by a lower

reactivity than aldehydes towards nucleophilic reaction for ketones. As expected, ketones

or aldehydes bearing a hydrogen on c-carbon resulted in low to very low yields (entries

4.6 and 4.7). Butyraldehyde, that had already low yield for trifluoromethylation, provided

only 5 % yield, which is not really interesting. These low yields can be explained by the

fact that TDAE is also a strong base and would readily deprotonate acid hydrogens in the

substrates, creating enolates, in the case of aldehydes and ketones.









Table 4-1. Compared yields between pentafluoroethylation and trifluoromethylation of
aldehydes and ketones
Yield with
Entry Substrate Yield (%) CF3112 (%)

O

4.1 90 Quant.





4.2 75 80





4.3 0 80 83





4.4 Q 95 73

0

0
4.5 & 0 55 68



0
4.6 50 50





4.7 / o 5 15









4.3 Perfluorobutylation of Aldehydes and Ketones

Since nucleophilic pentafluoroethylation of aldehydes and ketones with C2FsI /

TDAE system could provide good yields and comparable to trifluoromethylation with

CF3I / TDAE system, the methodology was extended with C4F91.

0 OH
S + C4F9I + TDAE DMF RI R2
R, R2 -20 oC to RT
C4F9
hv, 1 hr
1 eq 2.2 eq 2.2 eq RT, 12 hrs

Scheme 4-2. Nucleophilic perfluorobutylation of aldehydes and ketones

The yields obtained are very low: 35 % for benzaldehyde and 20 % for

cyclohexanone. Similar low reactivity of C4F9I / TDAE system was already observed in

the case of disulfides (Chapter 2). The fact that the C4F9I / TDAE complex is not very

stable and tends to decompose shortly after the addition of TDAE to the reaction mixture

may explain this low reactivity. Moreover the Sun Lamp that provided the light

irradiation produces a lot heat, this additional heat may be the cause of lower yields.

Table 4-2. Perfluorobutylation of aldehydes and ketones

Entry Substrate % yield







0
4.9 2059

4.9 d 2059









4.4 Conclusion

In the same manner than with disulfides and tosyl imines the C2FsI / TDAE system

provided very similar yields than CF3I / TDAE system. However C4F9I / TDAE system

proved to be not reactive enough towards aldehydes and ketones and provided really low

yields. The CF3I / TDAE methodology could be successfully extended to C2F5I. But

C4F91 seems to be the limit of this methodology in nucleophilic perfluoroalkylation of

aldehydes because the yields are so low that it is not interesting to develop further the

reaction.

4.5 Experimental

Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus

300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with

external tetramethylsilane (TMS, 6 = 0.00 ppm) as a reference. Fluorine (19F) and proton

(1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFC13, 6 =

0.00 ppm) as a reference for 19F NMR and TMS (6 = 0.00 ppm) for H NMR. Deuterated

chloroform (CDC13) was used as NMR solvent.

4.5.1 General Procedure of Pentafluoroethylation of Aldehydes and Ketones:
Synthesis of 1-Phenyl-2,2,3,3,3-pentafluoropropan-l-ol (4.2)

In 25 mL, 3-neck-round bottom flask, equipped with a reflux condenser and N2,

benzaldehyde (0.37 mL, 3.68 mmol) was disolved in 10 mL of anhydrous DMF. The

solution was cooled at -20 oC and C2F5I (2.0 g, 8.1 mmol) was introduce into the solution.

Then TDAE (2 mL, 8.1 mmol) was added into the reaction mixture. The color of the

reaction mixture became dark red as TDAE was added. The mixture was allowed to

warm up slowly to room temperature. The reaction was irradiated by a Sun lamp for 1

hour. White solid was formed as the temperature of the bath reached -10 C. The reaction









mixture was stirred at room temperature overnight. The orange solution was filtered and

the solid was washed with diethyl ether. The DMF solution was hydrolyzed with water

and was extracted with ether (3 times). The combined ether layers were washed with

brine and dried over MgSO4. The solvent was removed and the crude product was

purified by column chromatography to afford colorless liquid60 at 90 % yield

1HNMR (CDC13, 300MHz) 6 7.45 -7.70 (m, 5H, ArH); 5.06 (m, 1H, CHCF2); 2.87

(s, 1H, OH) ppm.

19F NMR (CDC13, 300 MHz) 6 -81.90 (m, 3F, CF3), -122.80 (m, 1F, CF3CFF), -

129.50 (m, 1F, CF3CFF) ppm.

1-Naphthyl-2,2,3,3,3-pentafluoropropan-l-ol (4.2)

1H NMR (CDC13, 300MHz) 6 8.05 (d, J = 8.4 Hz, 1H, ArH); 8.0 7.82 m, 3H,

ArH); 7.65- 7.32 (m, 3H, ArH); 5.89 (m, 1H, CHCF2); 2.85 (s, 1H, OH) ppm

19F NMR (CDC13, 300 MHz) = -81.54 (m, 3F, CF3), -118.15 (dd, J1 = 290.4 Hz, J2

= 20.7 Hz, 1F, CF2), -130.24 (dd, J1 = 290.4 Hz, J2 = 20.7 Hz, 1F, CF2) ppm

1,1,1,2,2-Pentafluoro-5-(2methoxy-phenyl)-pent-4-en-3-ol (4.3)

1HNMR (CDC13, 300MHz) 6 7.45 (dd, J1 = 7.7 Hz, J2 = 1.8 Hz, 1H, ArH); 7.31

(m, 1H, ArH); 7.25 (d, J = 16.2 Hz, 1H, ArH); 6.95 (m, 1H, ArH); 6.87 (dd, Ji = 7.5 Hz,

J2 = 0.9 Hz, 1H) 6.27 (dd, J1 = 16.2, Hz, J2 = 7.1 Hz, 1H); 4.66 (m, 1H, CHCF2); 3.87 (s,

3H, OCH3); 2.26 (s, 1H, OH)

19F NMR (CDC13, 300 MHz) = -81.40 (m, 3F, CF3), -122.25 (AB, dd, Ji = 291 Hz,

J2 = 9.9 Hz, 1F, CFF CF3); -129.12 (dd, Ji = 291 Hz, J2 = 9.9 Hz, 1F, CFFCF3) ppm









9-Pentafluoroethyl fluoren-9-ol (4.4)

1H NMR (CDC13, 300MHz) 6 7.67 (m, 4H, ArH); 7.48 (m, 2H, ArH); 7.36 (m, 2H,

ArH); 3.01 (s, 1H, OH)

19F NMR (CDC13, 300 MHz) = -78.62 (s, 3F, CF3), -121.29 (s, 2F, CF2) ppm

1,1-Diphenyl-2,2,3,3,3-pentafluoropropan-l-ol (4.5)61

19F NMR (CDC13, 300 MHz) = -84.65 (s, 3F, CF3), -115.97 (s, 2F, CF2) ppm

Pentafluoroethyl cyclohexan-1-ol (4.6)62

19F NMR (CDC13, 300 MHz) = -78.17 (s, 3F, CF3), -126.25 (s, 2F, CF2) ppm

1,1,1,2,2-Pentafluorobutan-3-ol (4.7)63

19F NMR (CDC13, 300 MHz) = -81.57 (m, 3F, CF3), -122.75 (m, 1F, CF3CFF), -

131.40 (m, 1F, CF3CFF) ppm

4.5.2 General Procedure for Perfluorobutylation of Aldehydes and Ketones:
Synthesis of 1-Phenyl-2,2,3,3,4,4,5,5,5-nonafluoropentan-l-ol

In a 25 mL round bottom flask, connected N2, benzaldehyde (0.37 mL, 3.68 mmol)

was disolved in 10 mL of anhydrous DMF. The solution was cooled at -30 oC and C4F9I

(0.75 mL, 8.1 mmol) was introduce into the solution via a syringe. Then TDAE (2 mL,

8.1 mmol) was added into the reaction mixture at -20 oC. The color of the reaction

mixture became dark red as TDAE was added. The reaction was irradiated by a Sun

lamp.The mixture was allowed to warm up slowly to room temperature. White solid was

formed shortly after the addition of TDAE. The reaction mixture was stirred at room

temperature overnight with the presence ofiradiation. The orange solution was filtered

and the solid was washed with diethyl ether. 20 mL of water were added to the filtrate the

two layers were separated and the aqueous phase was extracted with ether (3 times). The






51


combined ether layers were washed with brine and dried over MgSO4. The solvent was

removed by vacuum and the crude product was purified by column chromatography.













CHAPTER 5
SYNTHESES AND STUDIES OF TETRAKIS(DIMETHYLAMINO)ETHYLENE
ANALOGUES

5.1 Introduction

Our laboratories have successfully developed methodologies for nucleophilic

perfluoroalkylation of numerous subtrates.12,13,14,15,50 These methodologies consist in

reducing perfluoroalkyl iodides with tetrakis(dimethylamino)ethylene (TDAE), creating

perfluoroalkyl anions which can undergo nucleophilic reactions on different eletrophilic

substrates. The mechanism of the reactions is still not totally understood. But it is known

that as TDAE was introduced into the reaction mixture containing perfluoroalkyl iodide

and the substrate, TDAE formed a temperature-dependently stable complex with

perfluoroalkyl iodide. As the reaction temperature rose above these critical temperatures

(0 C for CF3I, -10 C for C2FsI and -20 C for C4F9I), the complex decomposed freeing

perfluoroalkyl anion, which only then reacted with the substrate (Scheme 5-1).


Substrate -20 oC Substrate
0 product
CF3I complex

TDAE TDAE2+ CF3 I-

Scheme 5-1. CF3I / TDAE complex

At this point, we have little knowledge about the complex and its decomposition. It

is not sure whether the product resulted from an attack from a free perfluoroalkyl anion

or from an intermediate form where TDAE is still involved. In the latter case, the

presence of chirality in the complex would induce chirality in the final product. This









would be particularly interesting in the case of reactions with aldehydes and ketones

where an asymmetric carbon is created from the addition of perfluoroalkyl group to the

carbonyl carbon. Since there is no preferential side of attack, the resulting ca-

perfluoroalkyl alcohol is a racemic mixture. The aim is then to synthesize analogue

molecules to TDAE, conserving the tetrakis-amino ethylene part and possessing a

structure that would be able to bear asymmetric carbons. The structure would be a cyclic

analogue to TDAE containing asymmetric carbons, as shown in Figure 5-1.


R R
R' R'


N N
R R

Figure 5-1. Structure of a chiral TDAE analogue

But the non chiral cyclic TDAE analogue -1,3,1',3'-tetraalkyl-2,2'-

bis(imidazolidene)- (Figure 5-2), would be first synthesized and studied to see if

comparable results than TDAE could be obtained.


R R
/ \
N N


N N
R /
R R


Figure 5-2. Non chiral TDAE analogue









5.2 Syntheses of TDAE Analogues

5.2.1 Synthesis of 1,3,1',3'-Tetraalkyl-2,2'-bis(imidazolidene)

Two analogues were synthesized where R were methyl group and ethyl group. The

one-pot synthesis involved reaction between N, N'-diethylethylene diamine or N,N'-

dimethylethylene diamine and N,N'-dimethylformamide dimethyl acetate64. The two

reagents were dissolved in benzene and were heated at 110 oC for 4 hours then the

product was collected via distillation under reduced pressure. The resulting products are a

pale yellow liquid for 1,3,1',3'-tetraethyl-2,2'-bis(imidazolidene) and a pale yellow solid

for 1,3,1',3'-tetramethyl-2,2'-bis(imidazolidene) with 40% yield for both products.

R R R
/ / \
NH -0 / bN N
/ benzene ___
NH --O reflux 4 hrs
NH -0 N N
R R R

1 equiv. 1.2 equiv. 40%
R= Me (5.1)
or Et

Scheme 5-2. Synthesis of 1,3,1',3'-tetraalkyl-2,2'-bis(imidazolidene)

5.2.2 Synthesis of 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene)

The other analogue we were interested in synthesizing was.


/


Figure 5-3. benzimidazole TDAE analogue








The synthesis of 1,3,1',3'-tetramethyl-2,2'-bis(benzimidazolylidene)consisted in 3

steps. The first step is the synthesis ofbenzimidazole65 by reacting 1,2-diaminobenzene

with formic acid. The reaction yielded 87%.

The second step was the methylation of the amino groups with iodomethane to

form 1,3-dimethyl-benzimidazolium iodide66 in 85% yield. The final step involved

deprotonation of the hydrogen on imine carbon, producing a carbene which recombined

to itself to form 1,3,1',3'-tetramethyl-2,2'-bis(benzimidazolylidene)67 resulting in a

brown solid in 50%.

H
NH 2 A+ H20
+ HCO2H + H20
NH, N
(5.2)

H
N /
S+ 2MeI >
"N "No p1

(5.3)



2 NaHl
>N i THF HN /N

(5.4)

Scheme 5-3. Multi-step synthesis of benzimidazole TDAE analogue









5.3 Attempts of Trifluoromethylation using the TDAE Analogues

5.3.1 Attempts of Trifluoromethylation using 1,3,1',3'-Tetraalkyl-2,2'-
bis(imidazolidene) instead of TDAE

The first attempts of nucleophilic trifluoromethylation using the imidazolidene

TDAE analogue were performed in the same conditions than with TDAE: Anhydrous

DMF was used as solvent and the analogue was added to the solution ofbenzaldehyde

and CF3I at -20 C. The reaction mixture color didn't become deep red as it was always

the case for TDAE. Instead the solution became darker yellow than the color of the

analogue. But the mixture seemed to discolored back to pale yellow few moments later.

The usual salt formation at 0 OC for CF3I / TDAE couldn't be seen by using the

analogue. The solution stayed clear throughout the reaction process. 19F NMR revealed

the presence of the trifluoromethylated adduct but in a yield lower than 10 %. Numerous

reactions of optimization have been performed but no more than 15 % of the product

could be obtained. The "optimized" procedure would introduce the imidazolidene TDAE

analogue at -40 OC, instead of -20 C, and the temperature was kept at -40 OC for more

than 40 minutes before allowing the reaction mixture to warm up slowly to room

temperature and stirred overnight. The reaction was irradiated for 12 hours.


R R CF3
N N
+ CF3I + DMF OH
N N -40 C to RT
R R
1 2.2 2.2 15%

Scheme 5-4. Nucleophilic trifluoromethylation of benzaldehyde using 1,3,1',3'-
tetraalkyl-2,2'-bis(imidazolidene)






57


R R
/ \
N N
PhS-SPh + CF3I + N N \ N DMF PhS-CF3
N N -40 Cto RT 11 %*
\ /
R R based on equiv.
1 4.2 2.2 of disulfides

Scheme 5-5. Synthesis of phenyl trifluoromethyl sulfide by using imidazolidene TDAE
analogue

An attempt of trifluoromethylation of phenyl disulfide was also performed. Only

110 % of phenyl trifluoromethyl thioether could be obtained, instead of nearly 200 % in

the case of TDAE. But the thioether may be resulted from the SRN1 reaction of phenyl

thiolate, formed by reduction of disulfide by TDAE analogue, with CF3I, since the

analogue cannot efficiently create trifluoromethyl anion.


R R R R
N N- + CF, SET N N +
rI)C N N N NN
R R
R = alkyl


I H20 (work-


R R
N, N !
--- \> + :!+ ;CFj +1
N N
R R

up) 11/202


SF3C N



R I R
R R

N N
>: + F3C

R R


R R
I I
N OH
R>LCF3 0=
N N
R R


Scheme 5-6. Possible decomposition pathways for imidazolidene TDAE analogue










The explanation of this lack of reactivity of the TDAE analogue towards CF3I may

be the fact that the cyclic TDAE analogues may give, after one-electron transfer to CF3I,

the corresponding colored radical cation. It seems that the radical cation is quite unstable

since the color disappeared. By decomposing the radical cation would probably give the

corresponding carbene and a new "smaller" radical cation.68 According to recent

studies69, the carbene should not dimerize to form back to the TDAE analogue but may

react with 02 to form a cyclic urea or with benzaldehyde to form an intermediate that

may give a bezoin condensation or the corresponding 2-benzoylimidazoline as final

products.70 (Figure 5-7)


SR R R










R
E c c vy h sPhCHh s rN

N N
N H N Ph
SR R R oe R


R R
NH
N CCHP



Scheme 5-7. Reactivities ofimidazolidene carbene towards benzaldehyde

The cyclic voltammetry experiment was also performed on 1,3,1',3'-tetraethyl-

2,2'-bis(imidazolidene). But the resulting graph didn't show any reversible oxidation

waves corresponding to the formation of stable radical cations (Figure 5-4), whereas

TDAE cyclic voltammetry graph shows reversibility.71




















-- ... --- "" ---- S --esel
3.ooE-06 2.00E-06 1.0E-O 0o. F00 -1.00E -2.oE- 06 -300E-06 -4.00E-B1 -S.00E-06




-2000


-3000



Figure 5-4. Cyclic voltammogram for 1,3,1',3'-Tetraethyl-2,2'-bis(imidazolidene), C =
3mM in DMF + 0.1 mM Et4NBF4 at 20 "C, scan rate: 0.2V/s

5.3.2 Nucleophilic Trifluoromethylation of Phenyl disulfide using 1,3,1',3'-
Tetramethyl-2,2'-bis(benzimidazolylidene)

The attempt of trifluoromethylation of phenyl disulfide with 1,3,1',3'-Tetramethyl-

2,2'-bis(benzimidazolylidene) only provided traces of phenyl trifluoromethyl sulfide. The

analogue may be either too stable or may decompose directly to carbenes since the

compound was synthesized via dimerization oftwo carbenes.

/ \

PhS-SPh + CF3I + N DF PhS-CF3
N N -40 C toRT trace
\ / trace

1 4.2 2.2

Scheme 5-8. Attempt of synthesis of phenyl trifluoromethyl sulfide by using 1,3,1',3'-
tetramethyl-2,2'-bis(benzimidazolylidene)









5.4 Conclusion

The idea of using chiral TDAE analogues to induce chirality in the final products

would have been an interesting project since industries are looking for chiral fluorinated

compounds as biologically active molecules. But the incapacity of these analogues to

generate CF3 anion from CF3I didn't allow us to develop further the idea.

5.5 Experimental

Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus

300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with

external tetramethylsilane (TMS, 6 = 0.00 ppm) as a reference. Fluorine (19F) and proton

(1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFC13, 6 =

0.00 ppm) as a reference for 19F NMR and TMS (6 = 0.00 ppm) for H NMR. Deuterated

chloroform (CDC13) was used as NMR solvent.

5.5.1 Synthesis of 1,3,1',3'-Tetraethyl-2,2'-bis(imidazolidene) (5.1)

N,N-dimethylformamide dimethylacetate (20 mL, 151 mmol) and N,N-

diethylethylene diamine (18.3 mL, 130 mmol) was dissolved in 80 mL of dry benzene.

The solution was refluxed at 110 OC for 3 hours. The azeotrope methanol/benzene was

then distilled out. The remaining solution was cooled to the room temperature and the

solvent was removed by vacuum. The product was distilled out under vacuum (bp = 86-

88 C/3 mmHg). Even though the melting point of 1,3,1',3'-tetraethyl-2,2'-

bis(imidazolidene) is around 48 C, it remained a yellow liquid66. Yield = 50 %

5.5.2 Synthesis of Benzimidazole (5.2)

In a 250 mL round bottom flasko-phenylenediamine (27g, 0.25 mol) is treated with

15 mL of formic acid (17.3 g, 0.38 mol). The mixture was heated and refluxed at 100 C









2 hours. After cooling, 10 % NaOH solution was added until the pH became just basic.

The crude brown product was collected by filtration and was rinsed with ice-cold water.

The crude benzimidazole was then dissolved in 400 mL of boiling water. About 1 g of

celite was added and the mixture was stirred while boiling for 15 minutes before hot

gravity filtration. The filtrate was allowed to cool slowly to room temperature and then

was placed in an ice bath for 20 minutes. The product was filtered and washed with ice-

cold water. The product was dried in the oven overnight to afford 25.69 g (87 % yield) of

pale yellow powder65

MP = 171 173 C

1H NMR(CDC13, 300 MHz) 6 8.10 (s, 1H, N-CH=N); 7.68 (m, 2H, ArH); 7.31 (m,

2H, ArH)

5.5.3 Synthesis of 1,3-Dimethyl-benzimidazolium iodide (5.3)

In a 100 mL round bottom flask, 1.4 g of sodium was added in small portions in 25

mL of absolute ethanol. After all sodium was dissolved, 7.1 g (60 mmol) of

benzimidazole was added to the solution, followed by 25g of iodomethane (180 mmol)

and 20 mL of benzene. The reaction mixture was refluxed for 15 hours. After the reflux,

the solvents were removed by vacuum. And the crude was recrystallized with ethanol to

yield 14.09 g (85 %) of 1,3-dimethyl-benzimidazolium iodide as a pale pinkish solid66.

1H NMR(CDC13, 300 MHz) 6 11.07 (s, 1H, N-CH=N); 7.72 (m, 4H, ArH); 4.28 (s,

3H, CH3); 4.27 (s, 3H, CH3)

5.5.4 Synthesis of 1,3,1',3'-Tetramethyl-2,2'-bis(benzimidazolylidene) (5.4)

In a 250 mL round bottom flask, 1,3-dimethyl-benzimidazolium iodide (10.09 g,

34.8 mmol) was dissolved in 100 mL of freshly distilled THF and sodium hydride (1.25






62


g, 52.2 mmol) was added slowly to the solution. The mixture was stirred for 3 hours at

the room temperature then 2 hours at 50 C. The solvent was removed by vacuum. 50 mL

of toluene was added to the dark brown residue. The mixture was heated to boil and was

hot-gravity filtered. The yellow filtrate was concentrated, n-hexane was added and the

solution was cooled at -30 oC for overnight. The recrystallized light brown solid was

filtered and dry to give 5.0 g of 1,3,1',3'-tetramethyl-2,2'-bis(benzimidazolylidene)67 (50

% yield)














CHAPTER 6
DIMERIC DERIVATIVES OF OCTAFLUORO[2,2]PARACYCLOPHANE (AF4) : A
NEW SOURCE OF PERFLUOROALKYL RADICALS

6.1 Introduction

6.1.1 General Information

Since their first designed synthesis in 1951,72 [2.2]paracyclophanes have been

considered valuable compounds for testing theories of bonding, ring strain, and 'r-

electron interactions.73-75 A number of methods have been devised for the relatively

convenient synthesis of the parent hydrocarbon, all of which require the use of high

dilution methodology.76-78 In addition, it has been recognized since the mid-1960s that

[2.2]paracyclophanes are useful chemical vapor deposition (CVD) precursors of thin film

polymers, known in the industry as "parylenes".79 Such parylenes are ideally suited for

use as conformal coatings in a wide variety of applications, such as in the electronics,

semiconductor, automotive, and medical industries. Parylene coatings are inert and

transparent and have excellent barrier properties. Parylene N, which is generated from the

parent hydrocarbon 1, has been found to be useful at temperatures up to 130 OC.

1,1,2,2,9,9,10,10-Octafluoro[2.2]paracyclophane,80 the bridge-fluorinated version of 1

(and known in the industry as AF4), is the CVD precursor of Parylene-HT polymer,

poly(u,a,a',a'-tetrafluoro-p-xylylene). The Parylene-HT polymer combines a low

dielectric constant (2.25)79 with high thermal stability (<1 wt % loss/2 h at 450 C), low

moisture absorption (<0.1%), and other advantageous properties.81'82 With such

properties and because its in vacuo deposition process ensures conformality to










microcircuit features and superior submicron gap-filling capability, Parylene-HT

continues to show considerable promise as an interlayer dielectric for on-chip high-speed

semiconductor device interconnection.

H2C- CH2 F2C- CF2




H2C- CH2 F2C- CF2

Figure 6-1. [2,2]-paracyclophane Figure 6-2. AF4

6.1.2 Synthesis of AF4

CF2CI F2C CF2

4 eq Zn
DMA, 100 C

CF2CI 3h F2C CF2
60%

Scheme 6-1. Synthesis of AF4

AF4 is produced in 60% yield in a reaction of Zn with 0.35 M

p-bis(chlorodifluoromethyl)-benzene in DMA at 100 OC.The mechanism of formation of

AF4 is shown in Scheme 6-2. p-bis(chlorodifluoromethyl)-benzene is reduced first by

zinc metal to p-xylylene intermediate 2, which reacts with itself to form dimer diradical

3. The two radicals reconnect to each other to form AF4.

The unique chemical characteristics of 1,1,2,2,9,9,10,10-octafluoro[2.2]-

paracyclophane (AF4) have been amply demonstrated by a number of recent publications

related to its synthesis,83-85 its chemical reactivity,86'87 and its role as the CVD precursor

of the highly thermally stable, low-dielectric thin film polymer known as parylene-HT.88

90










CF2Cl CF2
reduction CF2
P bimolecular F F

C-C bond formation F F
CF2CI CF2 F2CF F
F2C
1 2 3-extended



rotation
*
F2C polymerization
| F

A F 4 F
F 3-syn
F

F2C



Scheme 6-2. Mechanism of formation of AF4

Because ring-substituted derivatives of AF4 have the potential to produce parylene

films with enhanced properties, efforts have been directed at the synthesis of compounds

such as trifluoromethyl derivative (Figure 6-1).

F2C- CF2
CF3




F2C- CF2

Figure 6-3. Trifluoromethyl-AF4 derivative

Although 1 has been prepared by a traditional four-step synthetic sequence

beginning with nitration of AF4,76 a more direct method based on Sawada's free-radical

trifluoromethylation methodology appeared potentially attractive.91 However, when

trifluoroacetyl peroxide was allowed to decompose in the presence of AF4 in refluxing

CH2C12, although the trifluoromethyl radical indeed added to one of the aromatic rings of

AF4, no rearomatization to 1 was observed. Instead, the intermediate cyclohexadienyl










radical 2 proved to be uncommonly stable, so stable that it survived sufficiently long to

dimerize to a 57:43 mixture of the novel and structurally unprecedented diasteromeric

products, d,1- and meso-3, in a total yield of 60%

6.2 Kinetic Studies of CF3-AF4-dimers

6.2.1 Synthesis of CF3-AF4-dimer


F2C- CF2 F2C CF2 F2C CF2
1) 1 eq H202 (50%), 3eq (CF3CO)20

CH2CI2 -78 OC to RT. F3C CF3
F2C- CF2 2) reflux overnight F2C CF2 F2C CF2

60%
d,l : meso = 57:43


Scheme 6-3. Synthesis of CF3-AF4-dimer

The dimer is formed via radical addition of CF3' radical to AF4, forming a

trifluoromethylated AF4 radical that readily dimerizes into d,l and meso forms.

F2C CF2 F2C CF2

2 CF3 .
2 ,_ 2
F3C
F2C CF2 F2C CF2






F2C CF2 F2C CF2



F3C CF3
F2C CF2 F2C CF2


Scheme 6-4. Formation of CF3-AF4-dimer











The CF3' radical was formed by thermal decomposition of trifluoroacetyl peroxide,

which was prepared in situ by reacting trifluoroacetic anhydride with hydrogen peroxide.

(Scheme 6-5) Trifluoroacetic anhydride converts to trifluoro-peroxy acetic acid which

reacts with another molecule of trifluoroacetic anhydride to form trifluoroacetyl peroxide.

The resulting peroxide decomposes thermally into 2 molecules of carbon dioxide and 2

molecules of the CF3' radical.

(CF3CO)20 + H202 CF3CO3H + CF3CO2H


CF3CO3H + (CF3CO)20 CF3C(O)-O-O-C(O)CF3 + CF3CO2H


CF3C(O)-O-O-C(O)CF3 2 CF3 + 2 CO2


Scheme 6-5. Mechanism of formation of CF3' radical


F2C CF2
H
F2C CF2


F2C CF2
TTC ^^


< CF2

D,L







-64.5 -65.0 -6S.S


F2C ^CF2


F3C CF3
HH
F2C / CF2

F2C M CF2


MESO


- I
-i5.0 -56.5


-17.0 ppm


Figure 6-4. 19F NMR distinction examining the d,l and the meso forms of CF3-AF4-
dimers


^*V-f/^rLn


n


F2C










The two disateromers, d,l and meso forms, are distinguishable by 19F NMR, as

shown in Figure 6-4, the multiple peaks corresponding to the CF3 group having slightly

different chemical shifts. They could also be separated by column chromatography.

6.2.2 Thermal Decomposition of the CF3-AF4-dimer

The dimers are stable indefinitely at room temperature. But as they are heated, they

decompose to regenerate back AF4 and release 2 equivalents of CF3' radical. Two

different pathways for the mechanism of decomposition can be presented (Scheme 6-6).

The decomposition can be stepwise where the dimer is first broken into two molecules of

trifluoromethylated AF4 radical (A) and then CF3' radicals were eliminated, forming back

AF4 (path A) or the process is concerted and AF4 and CF3' are formed in one single step

(path B).

F2C CF F2C CF F2C CF2

path A

F3C CF3 F3C
F2C CF2 F2C CF2 F2C CF2
A







F2C CF2


2 + 2CF3'

F2C CF2

Scheme 6-6. Two possible pathways for decomposition of CF3-AF4-dimer

An experiment was performed to determine the mechanism of decomposition: the

dimer was dissolved in acetonitrile with an excess of 1,4-cyclohexadiene, in a sealed









NMR tube. 1,4-cyclohexadiene served as radical trap as it readily quenches radicals

present in the reaction by giving 2 hydrogen radical to form benzene. The reaction

moisture was heated above 160 C for several hours. If the mechanism is the path B, the

presence of 1,4-cyclohexadiene will not disturb anything and only AF4 will be formed

but if it's the path A, 1,4-cyclohexadiene will trap trifluoromethylated AF4 radical A and

A' will be found instead of AF4 (Scheme 6-7).

F2C CF2 F2C CF2 F2C CF2

\. N/ \ ^path A \

F3C CF3 F3C
F2C CF2 F2C CF2 F2C CF2
A

0 pathB 0




F2C CF2 F2C CF2
H
2 + 2 CF3H 21
F3C
F2C CF2 F2C CF2
A'

Scheme 6-7. Resulting products from radical trapping in different possible mechanism
pathway

19F NMR revealed a huge amount of AF4 in the reaction mixture but a small

quantity of A' could also be found. The presence of A', even in a small amount, proved

that the mechanism of the decomposition proceeds in a stepwise manner (path A). The

presence of the large quantity of AF4 can be explained by the fact that the formation of

AF4 from the radical A is much faster than the trapping by 1,4-cyclohexadiene.








6.2.3 Kinetic Study of Homolysis of CF3-AF4-Dimers
The study of the mechanism of the decomposition of the CF3-AF4-dimer showed

that the rate determining step is the first step of the mechanism where the dimer broke

down into two CF3-AF4 radical A. A kinetic study was the performed on the homolysis

of the two diasteromers to determine rate constants and half lives at different

temperatures and the activation energy of the reaction.
F2C CF2 F2C CF2 F2C CF2


F3C CF3 k F3
F2C CF2 F2C CF2 F2C CF2



0
1 a
F2C CF2

2 1
F3C
F2C CF2

Scheme 6-8. Kinetic study of homolysis of CF3-AF4-Dimers
The rate being first order, the slope of the plot of Ln of concentrations versus times

would give the rate constant of the temperature of experimentation, following the

equation below:

Ln([C]) = -k t

The experiments consisted of dissolving one diasteromer in dry acetonitrile with

an excess of 1,4-cyclohexadiene and a known amount of a,a,a-trifluorotoluene as

internal standard in a sealed NMR tube. The tube was heated in an oil bath at fixed









temperature. The tube was taken out of the oil bath regularly to measure the quantity of

the dimer by 19F NMR and the time was measured. From all the data, a graph of Ln of

concentration of dimer versus time was plotted and the slope of the linear regression gave

the rate constant k. The values of k at different temperatures are shown in Table 6-1.

Table 6-1. Rate constants of the 2 diasteromers of CF3-AF4-dimers

Temperatures (C) k (d,l) (s-1) k (meso) (s-1)

140.1 7.37 x 10-6 8.62 x 10-6

151.0 2.24 x 105 2.81 x 105

160.7 7.14 x 105 8.50 x 105

170.3 1.57 x 10-4 3.21 x 10-4

179.7 4.55 x 10-4 4.94 x 10-4



The rate constants of the meso form were always greater than that of the d,l form

but they are of the same order and pretty close. The difference in rate constants between

the two diasteromers seemed to decrease as the temperatures increase.

From these rate constants values, the half-life times could be calculated according

to the following equation:

k
TZ1/2 ---
Ln 2

The values are shown in Table 6-2. These half-life values confirmed the high

stability of the compounds at room temperature: the half-lives of both dimers are above

22 hours at 140 OC. But they decrease very rapidly as the temperatures increase, from

more than 22 hours to 25 min in less than 40 C.






72


Table 6-2. Half-life times of the homolysis of CF3-AF4-dimers

Temperatures (C) T (d,l) T (meso)

140.1 26hrs 7 min 22hrs 20min

151.0 8hrs 36min 6hrs 51min

160.7 2hrs 42min 2hrs 16min

170.3 74 min 36min

179.7 25.4 min 23.4 min



By using the Arrhenius equation, the activation energy of the homolysis could be

-Ea
obtained: k = A exp( ) K being the rate constant, Ea the activation energy and T the
RT

temperature in Kelvin.In the logarithmic form the equation beccomes:

Ea
Ln(k)= + Ln(A)
RT

By plotting Ln(k) versus 1/T, the slope of the graph would give access to the

activation energy.



















dl
A meso
- Linear (meso)
- Linear (dl)


y = -20.059x + 36.901
R2 = 0.9876


-7.5



-8



-8.5



-9



a -9.5



-10



-10.5



-11



-11.5



-12
2.20


y = -19.352x + 34.997
R2 = 0.9977


2.25 2.30 2.35
1/T x 1000


2.40


Figure 6-5. Arrhenius plot for the 2 diasteromers of CF3-AF4-dimers


% A


4*
A %









Table 6-3. Arrhenius plot data

1/T x 1000 Ln(k[d,l]) Ln(k[meso])

2.42 -11.82 -11.66

2.36 -10.71 -10.48

2.31 -9.55 -9.37

2.26 -8.76 -8.04

2.21 -7.70 -7.61



Table 6-4. Activation parameters for CF3-AF4-dimers

Ea (kcal/mol) Log A

d,l-Form 38.43 15.20

meso-Form 39.83 16.02



6.3 Kinetic Studies of C2F5-AF4-dimers

We were interested in study behaviors of AF4 dimers with a longer

perfluoroalkylated chains. Kinetic studies of pentafluoroethyl-AF4-dimers were then

performed.

6.3.1 Synthesis of C2F5-AF4-dimers

In the same manner as the synthesis of CF3-AF4-dimers, C2F5-AF4-dimers were

formed from C2F5 radical addition to AF4, the C2F5 radical being formed from thermal

decomposition of pentafluoropropionyl peroxide, formed in situ by reaction of

perfluoropropionic anhydride with hydrogen peroxide. Since pentafluoropropionyl

peroxide is much less stable than trifluoroacetyl peroxide, stirring overnight at room

temperature was sufficient to decompose the peroxide.











FC- CF2 FC CF, FC CF,
1 eq HzOz (50%),3eq (CF3CF2CO),O0

CH2C12 -78 OC to R.T. F3CFC CF2CF
F2C- CF2 FC- CF2 F2C CF2

50%
d,l: meso = 55:45


Scheme 6-9. Synthesis of C2F5-AF4-dimers

The dimer products are composed of two diasteromers, the d,l and meso forms, in a


ratio of 55 and 45 respectively. They can be distinguished from each other by 19F NMR


spectrum by examining the peaks of CF3 groups of the CF2CF3 chain, as shown in the


Figure 6-6


F2C -<'F IF-CF2 /^ =F


FFC CCF2
F2C~ CF2
H CF2CF3
CF2CF3 F3CF2C CF2C]
H H
F2C CF2 F2C -CF

F2C F2 F2C CF


D,L MESO









a3a -4 z "-4 34.1 -4* -M.4 -SE-0 pp


Figure 6-6. 19F NMR distinction examining the d,l and the meso forms of C2F5-AF4-
dimers

The structure of the meso form was determined by X-ray analysis and a perspective


view is shown in Figure 6-7.

































Figure 6-7. Perspective view (ORTEP) of meso-C2F5-AF4-dimer


6.3.2 Kinetic Studies of the Homolysis of C2F5-AF4-dimers

The kinetic studies on C2F5-AF4-dimer were performed using the same procedure

as applied to the CF3-AF4-dimers. The rates constants are summarized in Table 6-5.

Whereas for CF3-AF4-dimers, where the rate constants of the meso form

werealways greater than that of the d,l form, for C2F5-AF4-dimers (with the exception of

118.8 C, where k(meso) is higher than k(d,l)) the rates constants of d,l and meso forms

are almost identical, with the tendency for d,l rate constants to be slightly greater.









Table 6-5. Rate constants of the 2 diasteromers of C2F5-AF4-dimers

Temperatures (C) k (d,l) (s-1) k (meso) (s1)

118.8 1.16 x 10-6 1.80 x 10-6

130.5 5.02 x 10-6 4.63 x 10-6

139.6 9.53 x 10-6 1.00 x 105

145.3 2.31 x 105 2.14 x 105

151.3 4.16 x 105 4.10 x 105

156.4 5.86 x 105 5.83 x 10-5

161.0 1.09 x 10-4 1.10 x 10-4



The half-lives times at different temperatures are shown in Table 6-6. For C2F5-

AF4-dimers, the half-life times decrease very rapidly, from more than 100 hours to

around 70 minutes with only a 40 C change in temperatures. The decrease was much

greater than was observed for the CF3-AF4-dimers.

Table 6-6. Half-life times of the homolysis of C2F5-AF4-dimers

Temperatures (oC) z (d,l) z (meso)

118.8 166hrs 31min 107hrs 9min

130.5 38hrs 19min 41hrs 35min

139.6 20hrs 12min 19hrs 13min

145.3 8hrs 1 min 9hrs

151.3 4hrs 38min 4hrs 42min

156.4 3hrs 17min 3hrs 18min

161.0 77min 80min









An Arrhenius graph was plotted to obtain to the activation energies of the

homolysis reaction.

Table 6-7. Arrhenius plot data for C2F5-AF4-dimers

1/T x 1000 LnK (d,l) LnK (meso)

2.55 -13.67 -13.23

2.42 -11.56 -11.51

2.36 -10.09 -10.10

2.33 -9.74 -9.75

2.39 -10.67 -10.75

2.48 -12.20 -12.28

2.30 -9.13 -9.12



Table 6.8. Activation parameters for C2F5-AF4-dimers

Ea (kcal/mol) Log A

d,l-Form 35.65 13.90

meso-Form 33.01 12.60



The activation energies for C2F5-AF4-dimers are somewhat lower than that of the CF3-

AF4-dimers (38.43 kcal/mol for d,l and 39.83 kcal/mol for meso).















arrhenius plot


-9.0


-9.5


-10.0 -

y = -16.6237x + 29.0156,
-10.5 R2 = 0.9894 1


-11.0 -
d,
2 meso
-11.5 -
Linear (meso)
Linear (d,I)
-12.0 -


-12.5


-13.0-


-13.5 y=-17.9533x + 32.1679
R2 = 0.9941
-14.0
2.25 2.30 2.35 2.40 2.45 2.50 2.55
1/T *1000


Figure 6-8. Arrhenius plot of the 2 diasteromers of C2Fs-AF4-dimers









6.4 Conclusion

The AF4-dimers proved to be very interesting compounds. Their stability at room

temperature and their ability to release perfluoroalkyl radicals at high temperatures make

them an ideal source of perfluoroalkyl radicals where they can be used as initiators for

polymerization reactions of fluorinated monomers92 in which a high purity is required

since other initiators, such as AIBN, would introduce other functional groups to the

polymer chains

6.5 Experimental

Nuclear Magnetic Resonance (NMR) spectra were recorded on a Varian Unity plus

300 MHz Spectrometer system. The proton (1H) NMR were recorded at 300 MHz with

external tetramethylsilane (TMS, 6 = 0.00 ppm) as a reference. Fluorine (19F) and proton

(1H) NMR were recorded at 300 MHz with external fluorotrichloromethane (CFC13, 6 =

0.00 ppm) as a reference for 19F NMR and TMS (6 = 0.00 ppm) for H NMR. Deuterated

chloroform (CDC13) was used as NMR solvent.

6.5.1 Synthesis of CF3-AF4-Dimer

In 100 mL, 1-neck round bottom flask, 3g of AF4 (9 mmol) was dissolved in 25

mL of freshly distilled dichloromethane. Trifluoroacetic anhydride (4.2 mL, 30 mmol)

were added. The solution was cooled at -78 C and 50% H202 (3.4 mL, 10 mmol) was

introduced slowly via a syringe. The reaction mixture was kept at -78 C for one hour and

was allowed to warm to the room temperature. The reaction was stirred at room

temperature overnight and was then refluxed for at least 12 hours. White solid could be

seen in the flask. After reflux, the mixture was cooled to room temperature and the









solution was filtered. The crude was then purified86 and the two diasteromers were

separated via column chromatography (hexanes/ CH2C2 : 9/1)

6.5.2 Kinetic Studies of CF3-AF4-Dimer

6.5.2.1 General procedure

In a 5 inch NMR tube, 2 mg of one of the diasteromers of CF3-AF4-Dimer, 200 ptL

of 1,4-cyclohexadiene and 0.6 ptL of ca,a,a-trifluorotoluene were dissolved in 500 ptL of

deuterated acetonitrile (CD3CN). A rubber septum was place on the tube and the solution

was frozen at -78 C in dry ice / 2-propanol bath. The tube was degassed under vacuum

for several minutes. The NMR tube was flamed sealed. The tube was immersed in a

constant temperature bath for an appropriate time, then removed, cooled and analyzed by

19F NMR, with the concentration of the dimer being measured versus a,a,a-

trifluorotoluene, used as internal standard. The rates were determined for each isomer at

different temperatures.









6.5.2.2 Kinetic data and graphs for CF3-AF4-Dimer at 140.1 C

The following tables and figures show kinetic data and graphs for CF3-AF4-Dimer

at 140.1 oC.

Table 6-9. Kinetic data of d,l-CF3-AF4-Dimer at 140.1 C
d,l form

Time (min) C.103 (mol/L) LnC

8 3.75 -5.59

279 3.11 -5.77

545 2.82 -5.87

744 2.59 -5.96

1206 2.11 -6.16

1533.5 1.83 -6.31

1926.5 1.50 -6.50

2360 1.24 -6.69

2691 1.12 -6.79

2923 1.01 -6.89

Table 6-10. Kinetic data ofmeso-CF3-AF4-Dimer at 140.1 C
meso form

Time (min) C.103 (mol/L) LnC

0 2.09 -6.17

254 1.84 -6.30

453 1.67 -6.40

915 1.31 -6.64

1242.5 1.12 -6.80

1635.5 0.89 -7.02

2069 0.70 -7.26

2400 0.62 -7.39

2632 0.54 -7.52










83





-5.5
400 800 1200 1600 2000 2400 2800 3200


5.7




-5.9




-6.1 y = -0.00044225x 5.62532632

R= 0.99751858


S-6.3




-6.5




-6.7




-6.9




-7.1
t (min)


Figure 6-9. Kinetic Graph of d,1-CF3-AF4-Dimer at 140.1 C



-6.0
) 500 1000 1500 2000 2500 3000


-6.2



-6.4 y = -0.00051719x 6.16656971
R2 = 0.99951338


-6.6



-6.8



-7.0



-7.2



-7.4



-7.6



-7.8
t (min)


Figure 6-10. Kinetic Graph of meso-CF3-AF4-Dimer at 140.1 C