<%BANNER%>

1-Benzotriazolyl-2-Propynones as Novel 1,3-Biselectrophiles, Benzotriazole-Assisted Thioacylation and Synthesis of Energ...

University of Florida Institutional Repository
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 E20110221_AAAACQ INGEST_TIME 2011-02-21T20:58:02Z PACKAGE UFE0013389_00001
AGREEMENT_INFO ACCOUNT UF PROJECT UFDC
FILES
FILE SIZE 6017 DFID F20110221_AAAFJE ORIGIN DEPOSITOR PATH rogers_j_Page_27thm.jpg GLOBAL false PRESERVATION BIT MESSAGE_DIGEST ALGORITHM MD5
e0ce60caceda15036f676525b70b3201
SHA-1
cac8bc8fd833504a03540c1aa8df0682afb30631
9308 F20110221_AAAEXJ rogers_j_Page_07.pro
2553f62201803f1392382c3253b1d476
7e1bc641bf8a6a174223601ad4f0935860511635
8423998 F20110221_AAAESM rogers_j_Page_28.tif
e870eaafaf75ef81657d3336cff4c7e1
8d9f9559d171381afdb4e301aa526eb2011c4663
83141 F20110221_AAAFEG rogers_j_Page_64.jpg
1aacdad8f23b519c7a25e004c7a5e2cb
7099f7abc306b2b3d55032bdc23d8ec69db58ecf
7733 F20110221_AAAFJF rogers_j_Page_28thm.jpg
2bb2e24b1149678e0a96c3edbd86f07e
fabb8122f7678c92df91d79f34d0be3360cdad5b
47592 F20110221_AAAEXK rogers_j_Page_08.pro
9400199a65e9826a1135a3d9e406e40f
e7d3fab61379e9cb7431e0ed2cad4068440f100f
F20110221_AAAESN rogers_j_Page_29.tif
5badf0aca302539157598e3f7aa1cf0e
da86293db0528b6ab0cf2c7984ddc3eff8ec158c
27333 F20110221_AAAFEH rogers_j_Page_64.QC.jpg
62485f8290bfd9beea545877fe3a0db8
39ef312e47f92a6f55a76b7f8037350c0fc4dc9c
7424 F20110221_AAAFJG rogers_j_Page_29thm.jpg
984008c733ee054f45d496b112fcbb59
3842ab9230822aad56506ecb785f763f3b3d8931
54069 F20110221_AAAEXL rogers_j_Page_09.pro
7dd6e5073ad84f847c5300c46b082c92
8f88fd8309c6c958882462dbf15c0058abeb6e62
F20110221_AAAESO rogers_j_Page_31.tif
86f6857e5f077439fafebdc34fb19ab6
3d40049b9783a4dfd7de0f18df8e3bf7d2b2f322
82802 F20110221_AAAFEI rogers_j_Page_65.jpg
cc2d385a5eb9ebbad306c01ce868c3e1
c1c05bd8f319f97fb903d38e57159531d76ee59f
8409 F20110221_AAAFJH rogers_j_Page_30thm.jpg
c5f12dd40f24b7aeb643a3e45807a7f4
266129568da89d621b5704c00ae7416bfa8437ef
50291 F20110221_AAAEXM rogers_j_Page_10.pro
f71dba88e5b357f1f3668ca1ddcb203a
d6c96e42a69c6172619f658c283b88364cecb37f
F20110221_AAAESP rogers_j_Page_32.tif
0798206b58024c0b6f6387bb862a2722
e39d63173b1c3e1ef4b83d67dfed4f59858fee33
27144 F20110221_AAAFEJ rogers_j_Page_65.QC.jpg
76b372a4bda71fdd7986f3f9352bda36
ea77c9e6e8f7701a439d6ab393a029d1fde2c0eb
7298 F20110221_AAAFJI rogers_j_Page_31thm.jpg
44cf4be155a6da57fb62fb1ec1681ea2
f95c89cc07dfe8e5d67b570957924f3174fdaff8
33101 F20110221_AAAEXN rogers_j_Page_11.pro
fbdafbedfdcc62a8f288648f17de29b5
b4102e165e74442179c52de244d063083ce8d795
F20110221_AAAESQ rogers_j_Page_34.tif
058da3f26ace34b3564057b18d893286
54a35c8a3863e1bb3f4e84d85ee063204efb9dbf
88444 F20110221_AAAFEK rogers_j_Page_66.jpg
5608f8b0856bf78984fcd7916b42d1ca
95d7dcbce546c7b828503b2b863e06b921c82fc2
7448 F20110221_AAAFJJ rogers_j_Page_32thm.jpg
6e13a89ea6f80f53dda57fcd2bceb852
d95deb1990ce3182ee34434832097fb22f1b985a
4591 F20110221_AAAEXO rogers_j_Page_12.pro
7ef95a2a108ce6566ff2c9ee4402ed89
d8fad7b179477c2d3e7ad82a54a06b8c1aae1b7b
F20110221_AAAESR rogers_j_Page_35.tif
710ae82e6f06514646f3920dc3b0f1cd
3b109eff00c66550c56e79541fb22ddc7646bce0
28966 F20110221_AAAFEL rogers_j_Page_66.QC.jpg
32305719d2e178ea26297b46e160f2a7
1b1eb8263490f43b104ac9a00c3327908e2490eb
35775 F20110221_AAAEXP rogers_j_Page_14.pro
9c7a754be480a130cb539d9cf829d229
ce11f86edc08e9bc0f7550af1793d5040c6d0105
F20110221_AAAESS rogers_j_Page_36.tif
1842c4f67719874ead8b28385b74d9ba
b211c470775f7a4b8cebad74019879878282df6c
89493 F20110221_AAAFEM rogers_j_Page_67.jpg
2983201bf0ea789ec2f55820cfba77bf
8cc3bd18a5cf76db53d73bfe44991e60ec362bd8
6428 F20110221_AAAFJK rogers_j_Page_33thm.jpg
42d3963bce080863b97a719fe2782037
6ac3e50e09fb7508f5f255690277205d561ec787
41649 F20110221_AAAEXQ rogers_j_Page_15.pro
e3b7654749def09097bcf8be5b48c80c
0e94bb1b541f84b822e2dfbc66d273c4a9bcf02c
F20110221_AAAEST rogers_j_Page_37.tif
b4a5b834f5cf5f8f791446939b11f226
6e4f341a9fdf0cbc6fe7c6cbb00e36b80498473c
30158 F20110221_AAAFEN rogers_j_Page_67.QC.jpg
dd4656aeb88fa0d3761c2ba096d68367
791147992699d683bfbf24d65e488cbac752743e
7937 F20110221_AAAFJL rogers_j_Page_34thm.jpg
5b364f9ef6a330e0830dff14e3c4a837
425747107b0c138d6a9b8544e087894cfb4ce44e
37264 F20110221_AAAEXR rogers_j_Page_16.pro
4b721ced97bcd8a85ba9dc8b7c592fba
0a469fe73347079328b42612070106070a17e3f8
99432 F20110221_AAAFEO rogers_j_Page_68.jpg
022dd03b60ab146a750c36b781d607e3
bd1603118866facca85516a944fb5c49d0a12a74
8524 F20110221_AAAFJM rogers_j_Page_35thm.jpg
f48b577bc3dcdb8d5e3dda8c523f02f5
28453c22134204f3cc2dba9a1663301d6226a92d
34796 F20110221_AAAEXS rogers_j_Page_17.pro
0137c37ea14ecbebbfe9ec9387275cb3
8b9591097619f0a131d530d8fd93e46e894fefd8
F20110221_AAAESU rogers_j_Page_38.tif
5baf92e07349a986e6494124c0c6765a
68068e13222407ab812b3e26fbd0faf3aa47fc67
32772 F20110221_AAAFEP rogers_j_Page_68.QC.jpg
cb349f5813509f365f5d402192e5d28f
3515d9b777cb41c27fec151f274e1d12b48dae86
8333 F20110221_AAAFJN rogers_j_Page_36thm.jpg
344925d44c17c554f4cbe9f9ecfbcbbd
183a830e642af4d73b08d7ad1b71b7cffe07d5ac
41918 F20110221_AAAEXT rogers_j_Page_18.pro
739f4ef7f193d19dec03ae2c307dfc1f
870fdf84b50b15f719320f658958bc460adac08b
F20110221_AAAESV rogers_j_Page_39.tif
d46c3a23e87d006930713ef23b0acc86
f426752074c73c32567d52c02969f845b350363e
96105 F20110221_AAAFEQ rogers_j_Page_69.jpg
902ec0595736463e965c5f13cf381227
68337c63d39fd519a1f07a8305088ca6104f58b5
8059 F20110221_AAAFJO rogers_j_Page_37thm.jpg
4af1d73461e4af7a76f45793a3b90592
bc6e53d5f3b83664d3170cf8acfd787247b7c018
31750 F20110221_AAAFER rogers_j_Page_69.QC.jpg
658c57d0c9029e2f1f4cf6f723e275cc
585157c4d35bd114d16094a1c1a811d0a34294cd
49728 F20110221_AAAEXU rogers_j_Page_19.pro
04565d92b542f0e94648bbd91becf833
956002b586c9851ae304b6d593485482073741da
F20110221_AAAESW rogers_j_Page_40.tif
64626ab53303b2ef42bfa35c14271874
6a19945bdf57531ffeccef598074d3520b14b379
8218 F20110221_AAAFJP rogers_j_Page_38thm.jpg
39b55b57abd16b49c6fef8d448e4b667
08355a8ba582d1ec2dbf2ed85c289a3731cee029
95525 F20110221_AAAFES rogers_j_Page_70.jpg
c84911cf87e1c8ad663a76643776e910
6522747553f4aed9d366545a41ee90198725ff3b
41305 F20110221_AAAEXV rogers_j_Page_20.pro
385eb78979859a976aa892588b1225bb
2d96a7388269c145ee51d720301beaee24a58750
F20110221_AAAESX rogers_j_Page_41.tif
81ce3fa43d4f9d115a0d3527a9023ee3
bc281cb1c3c094359f08646bd057ba4ecaf35e21
2909 F20110221_AAAFJQ rogers_j_Page_39thm.jpg
caee77b00cb2e48f72767fcd630b835f
aec386b8e08ca4065b3b96b90bb05741e876af5b
30507 F20110221_AAAFET rogers_j_Page_70.QC.jpg
a3cce734888c0965e03db0294ecac369
813bd36fa20735e7882e70d396ff892921c274af
39012 F20110221_AAAEXW rogers_j_Page_21.pro
b5cc8c9c6db105097366c72f3fcfe508
33208757d29828127bf0c2c92f728a0e628a121d
1762 F20110221_AAAEQA rogers_j_Page_40.txt
1743d9e8607cf1063d1a6b100b321bf9
1ee1f96e0a3cef5ca3b227d80c9cb635ab36537d
F20110221_AAAESY rogers_j_Page_42.tif
902dd615f04ccea4add67bd5b86489fc
49ed10095d8d63f8ddcd4d696f1fe9d036c435d7
6170 F20110221_AAAFJR rogers_j_Page_40thm.jpg
6a778ef8734734ce7fd8346b1f457225
45df5732ce2680863898818ea216463fa5c0fc04
91474 F20110221_AAAFEU rogers_j_Page_71.jpg
44d4afabe8e20bc71f6ace5c4859b7e1
66ebd0bd61fd0df9b9a82942a5e4187f9fc44365
35647 F20110221_AAAEXX rogers_j_Page_22.pro
22b873236f802eb89df7f99196de2522
138936522d3fb69be3eecbda0cab60e9ec39c68a
1780 F20110221_AAAEQB rogers_j_Page_48.txt
f89ea268e5a51ee09e6ebdd7f604ad41
6a9541f0ab82804415dc012543fb76962398319b
F20110221_AAAESZ rogers_j_Page_43.tif
08e7a3473ca2c0c36a32d45e46c09e74
4775e0ce40c89e775c473ce91fdb05f73894a3dd
8141 F20110221_AAAFJS rogers_j_Page_41thm.jpg
832c0fed8e11ca49918aa1baef674150
d6bbdaaccd9c54db6c3a230bc2ec4d9db0bd5b96
90289 F20110221_AAAFEV rogers_j_Page_72.jpg
87794a7fffb689e0809e855d9c0f5893
af34eb7b89272f91e4fae90a3b5e9948077607ee
66361 F20110221_AAAEQC rogers_j_Page_53.jp2
59664a2014bd9ef18163cae8bebd8a6a
57231da4bb0b34255551c1e3e5f05963049cec32
48538 F20110221_AAAEXY rogers_j_Page_23.pro
84abb27295d88663da6bfa9276fc094d
f406d1c848a8cbd9a3877869752e8007dbdec556
7293 F20110221_AAAFJT rogers_j_Page_42thm.jpg
46e3beface56de13891e9bb54db92675
6d1a3effb85c53742dc8dca4ccf16faa17bf9921
29015 F20110221_AAAFEW rogers_j_Page_72.QC.jpg
009076409c7eaaa90fefce5e6e7be975
249056e6e9a3131a7ffaaf5bd100cbb553358456
164 F20110221_AAAEQD rogers_j_Page_53.txt
d4206ca6b1788a8473fcc2e0a9c76a39
126f250bf25780ee23881ca36b3165dbdacb6c53
1631 F20110221_AAAEVA rogers_j_Page_17.txt
92c7a8023a05361ab5560bd894601a3a
5fa636040a5f25a5ca9bb05ccfa219e270397de2
7422 F20110221_AAAFJU rogers_j_Page_43thm.jpg
e963669045b49e9ddf2cbcfc17375ec0
0559fa1252100914fd749cf14a1390eab10b6c8f
55693 F20110221_AAAFEX rogers_j_Page_73.jpg
79301d7f34465d6a655ccb257246cdd6
43b5c679fc8651d6babdec74867a85423c19da83
1602 F20110221_AAAEQE rogers_j_Page_07thm.jpg
b33353c7f10776bff61f3bfd28deed25
14fb7d455704dda65b5508138f09e96aabbdebe8
1728 F20110221_AAAEVB rogers_j_Page_18.txt
aeb03aa7dafa94e413a31d7136d787fc
c0f58ccb9f60f0dadd7575d44d15b1314dd51fee
39532 F20110221_AAAEXZ rogers_j_Page_24.pro
c8aabd6689a87fe805f7d9af6a163fb8
1025c6643bcc7dc7d9d990ecff92f20cb75be035
7767 F20110221_AAAFJV rogers_j_Page_44thm.jpg
d00da8932359163a48a56d1e91ffcee7
8144deeeba24acd399a3f05e173994478e40e75a
18359 F20110221_AAAFEY rogers_j_Page_73.QC.jpg
f2ed3bd12067badd18e44a6a5249c01f
4733b1f82ae42cf90446781f6b73b7eabbfef51c
44016 F20110221_AAAEQF rogers_j_Page_13.pro
1781da04d5ddef771103dd05c3820345
f6cdb083290d9e69e024c2f0d6a9b482aa17c0f4
85491 F20110221_AAAFCA rogers_j_Page_32.jpg
0f07a706b91f16dff3d842810dac8439
0730985257058e9b8b4a407fffd73be3f2101d7a
2308 F20110221_AAAEVC rogers_j_Page_19.txt
b39b9c5381bbca809f123d2468fcf918
67da8d43e346b618537ceeb1596f91f7d3a39ca8
7484 F20110221_AAAFJW rogers_j_Page_45thm.jpg
d9a15abda270d636232855f1a29aeebd
54d3e2d6d00a6ba707748bf38a27878e2c2f1ae4
103867 F20110221_AAAFEZ rogers_j_Page_74.jpg
4a49b58681b45cabf8b0ceb3c9f06b78
8e4783bbe9ddd0137223e6e89a2decf29fb04323
15710 F20110221_AAAEQG rogers_j_Page_07.jpg
f67368ded3c7ce84d318bc0e0e0841ae
22aea76a2de42d71a9db59dd4236c87e97fec767
28427 F20110221_AAAFCB rogers_j_Page_32.QC.jpg
3d37bc508ce05f071d5956a4e9bdbeca
358df06048d44a05dca437f1f111bb7bc80e8042
2292 F20110221_AAAEVD rogers_j_Page_20.txt
426b17e0c7ff73917c81ae28b098e86b
437c78c87727fe546e7e6660664af2dfab95161d
7500 F20110221_AAAFJX rogers_j_Page_46thm.jpg
2047f0fa1269f120ece6e995a51c0253
7998ad2f0640abc3c5d9544cd5303f27e14dde77
73397 F20110221_AAAEQH rogers_j_Page_14.jpg
173b78d3d00571534e0845365d4cae5c
11a828e58cef65c46f5e614f2c23c9dbc8eeef35
70028 F20110221_AAAFCC rogers_j_Page_33.jpg
1d117b8c6fd6f4e124bb874d3c273b3c
8236f1671780c52805be55fa2a4ce8bb0eaf28ff
1953 F20110221_AAAEVE rogers_j_Page_21.txt
f2097aaa9bcdd818238cad69cf07bce8
15b4fb6e011658adf6c4dfb1105a93a8e78c05f1
7808 F20110221_AAAFJY rogers_j_Page_47thm.jpg
8fd020bc85cf7a7760ba0a87bd430da8
6b79268c2791539c22c336e680f175203116b346
936548 F20110221_AAAFHA rogers_j_Page_43.jp2
a3a56b57bc9021827961033059ee02b6
c9354a0cbddc2c0e5560d5533c4d294aefa5ec49
47967 F20110221_AAAEQI rogers_j_Page_41.pro
e1c36eebb9f01613e8af3be3b467ca4a
0b9aaba82327fb38d825514a34313766c199ebd4
1817 F20110221_AAAEVF rogers_j_Page_22.txt
0b6a5023d739de4fd335ad226979ccd7
4d8ff36cc1764050f51b1e8a1ddd118c8169afb5
7989 F20110221_AAAFJZ rogers_j_Page_48thm.jpg
b7f678f9c63e914f8282d0e727cc0c5f
7c6d97582667c499548ae2745bd23f66832488df
966491 F20110221_AAAFHB rogers_j_Page_44.jp2
1de49aea424d9f68ea2dbbe9ae54267a
b742d9eb6ce44900d0a6e397cb4a4e6addea8e3e
F20110221_AAAEQJ rogers_j_Page_58.tif
fb80dacc70e2fb59fd2e64d7bc9175e9
ff17d886049a0b67304ea8e9498cdd90f6a36a56
23359 F20110221_AAAFCD rogers_j_Page_33.QC.jpg
8c9abe1840b9163556c05031faae22b1
4886e8293371256283eeaf0cc2ad1787e92f414c
1619 F20110221_AAAEVG rogers_j_Page_24.txt
fce7c9f5a077576d97cb49644b5d790d
f654d97aec48a4fd3da77f918a17c7ddd8137ca0
942171 F20110221_AAAFHC rogers_j_Page_45.jp2
18306f9b1b478d8b35937b285f04d0fa
9fb925e655475c60595dbeddd80a45b5672bc456
2001 F20110221_AAAEQK rogers_j_Page_76.txt
fa42d9442dcff0ed0800602f3fc6ddce
08ae74b2fed70c34478dca122429cf3caca8cc91
96013 F20110221_AAAFCE rogers_j_Page_34.jpg
e31825e4b8ea1ea23483afaa1c942b70
4ed1970c716de6547c442abc32617c5b3fb8e413
1691 F20110221_AAAEVH rogers_j_Page_25.txt
81f29aab95feec7e1ab93c5e8610fd6d
8e1947a5025a91ba196f447e2da957b2e0f59718
1016078 F20110221_AAAFHD rogers_j_Page_46.jp2
fce26616db7883e1fde86887ef337268
8d096074152bb5b0d88c6f8f25ab62d4d94ad36c
100963 F20110221_AAAFCF rogers_j_Page_35.jpg
04c5679cd3fd3f1551163b21ba1b8fb3
910df66c9119c7f40f08622093e988dbbeb30875
1657 F20110221_AAAEVI rogers_j_Page_26.txt
87a80d667fa097f25154c8e16712428a
b07e144c5b74c6d1b1ef87b0fb95785902ad337f
82578 F20110221_AAAEQL rogers_j_Page_24.jpg
1845ff674c7da2adf56355a0810e3aa3
f03d5301e9e065e30691333c0d0b38ab55faf953
920455 F20110221_AAAFHE rogers_j_Page_47.jp2
0ec96077a3ccd855affacd57eb297f79
fabd0f6e272d652de65cc64ffe3afc2b8ebad1f7
34828 F20110221_AAAFCG rogers_j_Page_35.QC.jpg
f094a768e6615504f169083263a19abd
467d9ed992e8135e7a23a09a6ed6935940fdc240
F20110221_AAAEVJ rogers_j_Page_27.txt
8f6106238066bae73e418971ccb96b66
1724b04891d71fe030d45e38f41d8f7a5ddfd2d3
730927 F20110221_AAAEQM rogers_j_Page_10.jp2
852b63905f5709705a285e7c06cc9a30
950289c18f764a3c24bb24479fed95e45b3e5ddc
969940 F20110221_AAAFHF rogers_j_Page_48.jp2
18e0cc76763158eaf295ebdc6aef6b83
29a42151e47165357d92bf2970e0c0a1a8e3755f
35520 F20110221_AAAFCH rogers_j_Page_36.QC.jpg
bcfd54a9d08f63cf6b7132b67b18dbe7
107936c1c667453fdef738eb6c19a0c881c3fe37
2523 F20110221_AAAEVK rogers_j_Page_28.txt
096b1332e629042877a600b629a033e0
c358728148bb09ab8f64bd2390e9d07a52f788f4
F20110221_AAAEQN rogers_j_Page_33.tif
f2b5c4b9e557090fd1dd2599f0c74120
18d8e6c30cfa9a8c3538240399842fba5bfd52db
1051963 F20110221_AAAFHG rogers_j_Page_49.jp2
a6db557db46d12586ebd238a098c7c18
81009dcd128f6c6373f436b45f5b38b79a656b05
98098 F20110221_AAAFCI rogers_j_Page_37.jpg
aaac2234cff467df2cff419976c898a1
329813e1b6cfb11f0f90f9878610531459f117d6
F20110221_AAAEVL rogers_j_Page_29.txt
361394e87d7b7e974ce6e78ce2a7fd1a
66368d248a8bda776d7a829fd94e43e3118bed9d
30080 F20110221_AAAEQO rogers_j_Page_71.QC.jpg
5baa97ac70f587f9bc4364f411562af3
c64caf86341dd289e97cc0c126d87132d93910a4
1002771 F20110221_AAAFHH rogers_j_Page_50.jp2
7cc70322e48d58f5e35c9657a88d811f
b142a1c379b14b005418e39aa76b38fc6d72aea1
104645 F20110221_AAAFCJ rogers_j_Page_38.jpg
50fb44613eee21048f96885c046daffc
ffce0d6d52d8239436f80e7c5f3f1839a752431e
2372 F20110221_AAAEVM rogers_j_Page_30.txt
35194daf2ae706a6c2055f83fb4a10cd
fe74f551dca0fc23d7306f1e9951eaf1cd17c005
1172 F20110221_AAAEQP rogers_j_Page_62.txt
c4a7aaa52715806efe75b435d1bb35bd
cb4bc7044fa2650a16c402e7f19a7d44d6edb643
35185 F20110221_AAAFCK rogers_j_Page_38.QC.jpg
5e2ee479d488446e4a450799d7a0a99b
0a46bb9b44fd2fd5933a242f866c3f29652bdcdb
1933 F20110221_AAAEVN rogers_j_Page_31.txt
c6a9cb775f8bee6e13a74ec54ec38bb4
5241a2a9dc017d674770563979aaa50411c6d989
6069 F20110221_AAAEQQ rogers_j_Page_81.pro
b4a901732ef656887fe20adc3b46c611
6b37e53748d6573de9be67f36dec966f03958e48
1051935 F20110221_AAAFHI rogers_j_Page_52.jp2
86b3183fbdf3c3a48434ef4ccbd81b7a
7223f5d4890e853c118d9cfbfe2aa16366ad46a4
34934 F20110221_AAAFCL rogers_j_Page_39.jpg
bfdaf5719d34702666fd4af353dd7458
406811cee327f462b40478df406f419a193027e1
1606 F20110221_AAAEVO rogers_j_Page_33.txt
f19d11c205a6ff3bdfe14b0b4878efa8
55b97ac216ce81d39a697960c458fcb03c9d0443
27830 F20110221_AAAEQR rogers_j_Page_24.QC.jpg
d82fc5721223895d8a957397f9d41e8f
333ccb48cf13d1f2c87455a5c630b1f93ca12368
808177 F20110221_AAAFHJ rogers_j_Page_55.jp2
5618162c5439ff67e00ad7031060bc3e
820f79a6cc58cbd21ba2ea3f202a9c09de748d8b
12325 F20110221_AAAFCM rogers_j_Page_39.QC.jpg
15ead4c27b424f563735993f0a9f12a2
35f472fe2a6f50910433b8eebf1507593055cf9a
1820 F20110221_AAAEVP rogers_j_Page_34.txt
0996eebbfc0dcc8d33228d08fe00dd0e
1fe2e16594f2852059deebe56341266bf6a171ab
913356 F20110221_AAAFHK rogers_j_Page_56.jp2
c37cc6449c07f8a07c5952845e0cb527
02b5e9daadb322762c76697258e2768f64de26a1
23389 F20110221_AAAFCN rogers_j_Page_40.QC.jpg
8a8709785cdaff1d6792d5286ae06713
f058bcd771d4741d34493cf190c2a0c20cc3af46
1901 F20110221_AAAEVQ rogers_j_Page_35.txt
72fbe83f10f417279d135d9b5fbf0b74
c5b3a1cbd94474163eac16e66367ff13f5161729
F20110221_AAAEQS rogers_j_Page_30.tif
9005b4333ecc4786c5d54fe2fd72b047
8161538fa1d35d841225bb5b74b49d1809e1b399
1051965 F20110221_AAAFHL rogers_j_Page_57.jp2
2ffcb8315223631b656f6b441fc08048
0eca3c3fa12bd1bd7c3d9bbcc04c41b53bb55e63
95684 F20110221_AAAFCO rogers_j_Page_41.jpg
3e80c9c6337b006e4fa87579e126d413
114027a319f6134ab1f978af3263fcf2b78ea8e3
1880 F20110221_AAAEVR rogers_j_Page_36.txt
0d349837352f6da6de72eb0d7bbee5e2
7a076593fc3079bb5718c0fb584570ebeefdac37
98957 F20110221_AAAEQT rogers_j_Page_36.jpg
42bfee8740258f8591ddf065955f159a
baae031b5f2e9beb465867e2281f055a25316aac
741826 F20110221_AAAFHM rogers_j_Page_58.jp2
402ec8ed8fcc73a6f21906f5ffda34b2
a66874baaf6d9be53bcbc2f0e07a6d2fd3507609
31862 F20110221_AAAFCP rogers_j_Page_41.QC.jpg
87818f0c7a5c2da23c28b04430d15edd
8a74be84bf134242e627578e74cafee39fd274f7
1832 F20110221_AAAEVS rogers_j_Page_37.txt
8c40160d43f322bb0834ba3ecdb7d3cc
85b9a94132a09ccdbeee5e4b94ab61fefa4a1b10
31704 F20110221_AAAEQU rogers_j_Page_34.QC.jpg
a5b96443505ac4f18aff1a1b0dfa4fc7
804e43cb8091a54deae2e60abee904f91ec02d29
978609 F20110221_AAAFHN rogers_j_Page_59.jp2
6404f338c4d45e246f4a528637c98525
51a96a65dc23554db0f94a00e4fd277b21bf1237
88147 F20110221_AAAFCQ rogers_j_Page_42.jpg
61465137001f751cf2defcda3c42b9d7
413cf54af17867df4c2f3c6f9a469143eb42a689
650 F20110221_AAAEVT rogers_j_Page_39.txt
b9eb684b885e69165fe3e6b38ceb9643
3aecd733c38411655e0f67533a06d7baa78e0ca5
71729 F20110221_AAAEQV rogers_j_Page_40.jpg
21daaf35aa6d17f92a6d53c09ba290a2
3ae5e4da2b73a22430c4de0dee08af914af9bfa1
819897 F20110221_AAAFHO rogers_j_Page_60.jp2
11b2985c5fc07a08b5fd1ac71dd9caee
15047a5d3a399cdf8b56ca99e14700f8749936cb
30054 F20110221_AAAFCR rogers_j_Page_42.QC.jpg
8a06a1f65c338c38a34f4a1b6b2a2460
529e69d848dc109cbb1cf04162b80591cdc9c8ab
2077 F20110221_AAAEVU rogers_j_Page_41.txt
4b3737116bde5c1b8ea88e55cb0dd251
c86449086782653f258ce21d653ce27d27f16718
222 F20110221_AAAEQW rogers_j_Page_04.txt
afd28cab8cbf4640fb94e591ee0aece1
b0e0c02539d96b3e3e854907391948a4c7f76c8f
1037848 F20110221_AAAFHP rogers_j_Page_61.jp2
41e07788e5406e76b53596b1aadc398a
df468deab11190baeccbbd438ef41f3d9a805be5
88187 F20110221_AAAFCS rogers_j_Page_43.jpg
f8f6ffd4d4748d8f4b9322a4ad50d951
775782ece08ad347ae136e9160bcade1ea1f2274
1994 F20110221_AAAEVV rogers_j_Page_42.txt
09e392463a36d03fe64991503f764793
0fb60c6784fab15cef18c7984c553533367c7e7a
1970 F20110221_AAAEQX rogers_j_Page_38.txt
8f16255c15cdd9595ca2eb552e79ced4
d65ca744463c503e4db90082776398d295556a7d
578394 F20110221_AAAFHQ rogers_j_Page_62.jp2
9b141c75cd9b9d052dac9cbcd87afb3b
05aa7ad8991959b75f78a1046556470d55f455db
29209 F20110221_AAAFCT rogers_j_Page_43.QC.jpg
c0022ab1ac647d3ce2685536f05404e9
5ff41787e2bca0e6054e0ce188bf5473567cdb24
1902 F20110221_AAAEVW rogers_j_Page_43.txt
97b4df526f34e27b73b78a890b4e6078
0a3c70e24e4e67258f23b3021ecb74aa9789af25
43948 F20110221_AAAEQY rogers_j_Page_43.pro
73fe7d4561a3fcb3c4bf8e23a4eda602
93cd118e195d85a21f2b4108c1cdc844794a9688
773228 F20110221_AAAFHR rogers_j_Page_63.jp2
f8ca893616879ff411139e61f96b8738
d88c19ff29d9a839e0b10f42733fe6165507130d
90849 F20110221_AAAFCU rogers_j_Page_44.jpg
cbac709ae2862fcc0e6e0187ce6f3d47
3c985b1a5800f877e859fb230f4391cfb8a536ef
97040 F20110221_AAAEQZ rogers_j_Page_48.jpg
57f8c0ebd6b6aabc6c0d196207d0db81
a69f5afeec8705289684346389f7105b7a3fab46
876072 F20110221_AAAFHS rogers_j_Page_64.jp2
8ec3d47754ba924d174f3953249bf523
dc2971bb6df636983e75016b8c9b22e01545f9a4
28341 F20110221_AAAFCV rogers_j_Page_44.QC.jpg
61d854e94105691b2aa80337319c5220
f4d696b7dc1d554ba05e4878e67366a13164b0e0
2194 F20110221_AAAEVX rogers_j_Page_44.txt
0a50c78eaa07c990e650fa259f79a4b2
a3bf9ec591a718250528bc745f76d4b9697bc631
840134 F20110221_AAAFHT rogers_j_Page_65.jp2
8fad9e6ab80fed4feb1f10f6ba10ed34
22e5c6aadbe570a1464ce5076ed028f1016608b6
89395 F20110221_AAAFCW rogers_j_Page_45.jpg
2c05b4b73fab10d034f1eff6c1c1aea7
a7f90a8cfa05e37a62db47a83b63fe1b17c2ca0b
F20110221_AAAETA rogers_j_Page_44.tif
376501b0dc4885cab26d206740d2d842
bf6e5d93e9b46e13fb2780dcb69693f90457a24b
1800 F20110221_AAAEVY rogers_j_Page_45.txt
71494b39b70366b6ccaa3c4fcfb1b0e2
f1bdafccbcd65413e97d16a04a469897dbb0a22f
917564 F20110221_AAAFHU rogers_j_Page_66.jp2
080bce69c78d5706b777727e8f10049e
bb9e82b4013025b27354788e3d175ac58583b7c3
29521 F20110221_AAAFCX rogers_j_Page_45.QC.jpg
71cc01e237fbad819bc400925c5f0108
49b5b2a1d08ef3aa4426dca160f783ca6c52a053
F20110221_AAAETB rogers_j_Page_45.tif
3b472ddcf5247041f052e661e3a8186a
a0365c00389f27920abe6195ea792d2e3afdac76
1908 F20110221_AAAEVZ rogers_j_Page_46.txt
9be5e30e53850a28fb0b43a80d5bde86
c6d302fd094b8c8b7c22d0a7f6262f91ef01ed1d
973306 F20110221_AAAFHV rogers_j_Page_67.jp2
eb973e6da988bd00332197b1823bba56
38b6b77d4b5d1f4e3ca277cb906dfd7cc97c4dc9
96069 F20110221_AAAFCY rogers_j_Page_46.jpg
aa6197c35ef6fc6ba6332a6c5e73807e
232e844c9af309480662249f33bfea9d307b0b01
F20110221_AAAETC rogers_j_Page_46.tif
bc5db97c620188d1ad6419a4d3bdb51e
81ea2f98e18954bc5c9c471d4b5621f3db611e73
93386 F20110221_AAAFAA rogers_j_Page_03.jpg
b5687c7118d9a928bd785912e12a4f5f
233f9eccf36cc15389a2c88fc34de175bd15e69a
1051975 F20110221_AAAFHW rogers_j_Page_68.jp2
6ffa5ec2a00d8c41239fd6d04b0612d6
09ad70ea0b96ae1afdd12824e60e05ea2c14e4f6
30811 F20110221_AAAFCZ rogers_j_Page_46.QC.jpg
3df19981a937a38b653414c687da3b3e
99ebc42d1232c6474c833f1dc3451d71ede7811e
F20110221_AAAETD rogers_j_Page_47.tif
c058ac2eba7f51058689339319b17bd5
17e24de32cee2371395aa157670d084715066934
35968 F20110221_AAAEYA rogers_j_Page_25.pro
f564ad8bf87fb59b4c8304b4a2047965
424a3e4c962b4e0b72e55e370c79ddfb15408a19
1010167 F20110221_AAAFHX rogers_j_Page_69.jp2
3f2f6875448315f0187c8b2a8956257c
4efc6a5d474bc2185198c677252b54f46b710f5f
F20110221_AAAETE rogers_j_Page_48.tif
f7d62f96d96fef190efa80f63528b515
b651537b6596d90820581875e786d9108c47abec
38679 F20110221_AAAEYB rogers_j_Page_26.pro
d8b4a15482d601ca1d180917fce0bac1
590dd2156cdeb2dd9bd8e29a4cb115c8722a2709
30332 F20110221_AAAFAB rogers_j_Page_03.QC.jpg
beaa625baf30a7bb3f352422548c652e
c33046458d9c078eed7518752ac5fb01cd8de06e
982926 F20110221_AAAFHY rogers_j_Page_70.jp2
e12cd0065bad51587ed401ca6ab52e12
fbf0d96bd80329f7b3f5b8798f01dae1a23ff7b7
31396 F20110221_AAAFFA rogers_j_Page_74.QC.jpg
3da0afec9e9055183cd09b54dc3d96ef
c2f9518594b0d77e768c4bf0a84d1d7316f377bb
F20110221_AAAETF rogers_j_Page_49.tif
a9ba5e0207c84a7a53c4055f093dfb6c
eae9ab9f66b5b031eefb5ce0e26091017bf7987a
31989 F20110221_AAAEYC rogers_j_Page_27.pro
885d99c99757d6c88d63378af5f4cc65
4177e57136ea48978bf392a599cd6849de76165b
14579 F20110221_AAAFAC rogers_j_Page_04.jpg
114c94ebc042698abe5663eba4a5096b
bcbd8b0b9c745d4e1378225db167a134b85ba4b6
952869 F20110221_AAAFHZ rogers_j_Page_71.jp2
0cf6477ac11c6d3fcba8b67e06cf5f0e
1af6fbdd4a1f857adaf84dec1a2cee31a73a4929
108496 F20110221_AAAFFB rogers_j_Page_75.jpg
7f756cc7df86192f57f58707d79ca0b4
1b32f04f4ca5a14d15cb6201e22d668559ec17d0
F20110221_AAAETG rogers_j_Page_50.tif
748b5c4cc6249f74f3f557297e2c9c2f
244fdb4141b4685bff2a03d6752c8ca9ba88aebe
47904 F20110221_AAAEYD rogers_j_Page_28.pro
8fa892a179f9e7904c5d5ac73c4a6590
832fd85a54c060b99ea7ea5dad8b7d42c87b9408
5406 F20110221_AAAFAD rogers_j_Page_04.QC.jpg
9ca2ec2a31be4d28d88a6e77b9f28fe5
ecd5b7bbe7f0ad28cfbe754507052b9db521d4be
34833 F20110221_AAAFFC rogers_j_Page_75.QC.jpg
24b4d1e5cd273978bf397ef43262c734
7bfceef31c4a0d47b3978d9a1a4b29e941d69264
42585 F20110221_AAAEYE rogers_j_Page_29.pro
8fa8a056152ecf855d11323ad0d4493c
d67e384e75ea9a24bb88b44cff8b38d56f7d4355
77492 F20110221_AAAFAE rogers_j_Page_05.jpg
aff2d7c78f4eff48dfc811d63352e425
b2315c4891b775952b6de7967617e5be6cb4eb2c
F20110221_AAAETH rogers_j_Page_51.tif
48533a2b7e45ad8dd35800eda1084ed2
28441d742dcf1e7de452c45c7cd456bc17fa2326
7951 F20110221_AAAFKA rogers_j_Page_49thm.jpg
29698dfc61ff4dd5d2d08916f30dd5d7
2e869f7876be78007a3e8ec67859118eb6a8f04d
100435 F20110221_AAAFFD rogers_j_Page_76.jpg
b5b3808b3afc90a1514c71e54e09f8a3
ece9c7bd5077c4686015234f66d9ddc68dc6872b
53400 F20110221_AAAEYF rogers_j_Page_30.pro
cb4c00552806fc53a1c84ef6a93bc737
d9095dc2096d612f7a60d5cbb10c7f56b90b4f86
19823 F20110221_AAAFAF rogers_j_Page_05.QC.jpg
d29bc5935b90eeb7b186ed1e378536e4
ab8764682c331bcb33cdee97a33e8c6d8795447d
F20110221_AAAETI rogers_j_Page_52.tif
b5160d473aa1ea205e8aecc454326687
97afe9ceb938ef038b93a0279cf5442dd137573b
8385 F20110221_AAAFKB rogers_j_Page_50thm.jpg
5abf064ff774f2a90bbc17911d9c2aa1
501a8e10d98b9ad37d0f96cba07a413980af9c9e
32525 F20110221_AAAFFE rogers_j_Page_76.QC.jpg
5991677a8c5d4389f2e19198f2c2bbe0
f284b00961ada5a10ebe297f7171944fc68bc7ce
40756 F20110221_AAAEYG rogers_j_Page_31.pro
26bb4099f80c477c9e3571d25ebf5cf6
cf920c7aa7be12efb7211e83991268f9771ee124
91703 F20110221_AAAFAG rogers_j_Page_06.jpg
90ca21a01f04413fedb2898e5673df3b
3f51f31943e1fd30b48c8ee0635145cd6cf58fef
F20110221_AAAETJ rogers_j_Page_53.tif
24aca8094dac8147686688f7fc0fa24b
7ec55f4d43e9762b347210fce0d7cf695fb8144e
7362 F20110221_AAAFKC rogers_j_Page_51thm.jpg
b2f82ff5034af3aee1bd5b5b8fe0ff92
ea9b69876a81fb7c42b21d813cab58d8a6f73ca1
109284 F20110221_AAAFFF rogers_j_Page_77.jpg
8adc4c6963ae11a92b356c9162c89a21
a9f60a64f657e18a7375c8b0391a82e6a60e06a0
42160 F20110221_AAAEYH rogers_j_Page_32.pro
11435ebb611cd2a62e3213faa512c621
1b34802d2c06b659d23744d7401540dcea598fd9
23242 F20110221_AAAFAH rogers_j_Page_06.QC.jpg
aee39c644a0354c56bb1d1bbd3379ff9
c6f86439280c0b0171964069c6e90e357fcfe0b6
F20110221_AAAETK rogers_j_Page_54.tif
5734c7abff588cd75ad97ae4268b993d
cdc18559ad823f6559a0f1b4adbfabc66c206827
8603 F20110221_AAAFKD rogers_j_Page_52thm.jpg
003c4ed135af0a476b2173fd81497e90
760e156953e0b044837ae22dc4b06840be7bc7b5
29462 F20110221_AAAEYI rogers_j_Page_33.pro
bf6773b616bd4ff8c9f50ea5824ee9cb
b9bcabaf781f1b055802e46ba2993f5eb1013c11
4948 F20110221_AAAFAI rogers_j_Page_07.QC.jpg
837a4239e2fed69799ccced967a113f2
12dcdc7e9e857ef68cc04a199418b82e3b1665b0
F20110221_AAAETL rogers_j_Page_55.tif
4a5fbe56b71e9a198f1e072c5bd8fb44
4329964d6743e682827c296d8234d1d748986310
963 F20110221_AAAFKE rogers_j_Page_53thm.jpg
33809d965d3031d6f1792ebe15ec98f1
308e4ae35eb84ee0eb3655e7d02f07e41583dcd4
32380 F20110221_AAAFFG rogers_j_Page_77.QC.jpg
96b550029b14ef7d6569a194ec81bc8f
9820ea1bbf4f0f92a93c4ac93fb8c43ab1daca21
45019 F20110221_AAAEYJ rogers_j_Page_34.pro
6039fbd2e863d7e5f788435008cd2d76
d5cfa987a11f4f773d9fd7f9652090a13465196f
61024 F20110221_AAAFAJ rogers_j_Page_08.jpg
9732ea174ec3e018cff59664c77e538e
185a7a6a7927abd2db5eb5de66bce797d3d0bc45
F20110221_AAAETM rogers_j_Page_56.tif
bcaa1752da594fdba5947d020cd0e961
97e34b102764e219577ec15911889d29a22773de
7260 F20110221_AAAFKF rogers_j_Page_54thm.jpg
b605f7c75b1f045a59df92447743458e
3de1cd8395128ac9dd6c1872089c069583b1eb7a
115849 F20110221_AAAFFH rogers_j_Page_78.jpg
147250a40dbbaeb2350098a93c28ae49
3df919046ad14346dfa7afa360d5a2c8b973ce4e
47799 F20110221_AAAEYK rogers_j_Page_35.pro
71168db2e401296f6462cdb70ed67467
360e775058a5c911eba9063a2251fa102c950de7
18156 F20110221_AAAFAK rogers_j_Page_08.QC.jpg
8a5ac62f2e901a0d8cadeda50e0fd1f7
ade66922ecb8ed27f57213e231edeb3cdd1f2b5a
F20110221_AAAETN rogers_j_Page_57.tif
b61bf2cae2ffba19f3d05fca1c2c7bed
a9a2679cc17532c8e5d75549fff184efd4b00a02
6755 F20110221_AAAFKG rogers_j_Page_55thm.jpg
90d9d65d8e9494b324ce0adb392737aa
e79959b5c8a985d31796a89c736c628f4cae1f8f
34484 F20110221_AAAFFI rogers_j_Page_78.QC.jpg
1adb1adb8e19369c37e6889a80e4e30d
ac88b485d6366ccae9672691994aa7f95e0ee7aa
47477 F20110221_AAAEYL rogers_j_Page_36.pro
ca15e748047ac0d46883b8f80013b7d6
0ccb3aa2b8455f89a5b5b85c1d28417fde85090f
78707 F20110221_AAAFAL rogers_j_Page_09.jpg
edb2689e231b9714626b2597428ea48a
42f421917e1f3328e6fdad0efcff352947bb6534
F20110221_AAAETO rogers_j_Page_59.tif
d0bfeeda576218f0644e3a04b3e31d8b
a2cb7378367a31ac1def205dc112a66b89578b75
7427 F20110221_AAAFKH rogers_j_Page_56thm.jpg
8640a87caeb38cf54bdff91bea61a679
02fe7dea91120842f0eaa0813c008934afdb5207
96562 F20110221_AAAFFJ rogers_j_Page_79.jpg
4524d577852843147c63570553073678
b728101c5eeb9e928f441afb440b07a2e0867c5c
46120 F20110221_AAAEYM rogers_j_Page_37.pro
de101cafde9678aa164c2e8450f1f1a0
7f8ea38de7c07ce62ace715652229780fc9e19c3
24069 F20110221_AAAFAM rogers_j_Page_09.QC.jpg
8b9bc1cf9ff3dc35a225ce599470520f
bcff526e6c7228833f05d4f1edeffa05336cb01c
F20110221_AAAETP rogers_j_Page_60.tif
f20364923632d9bdc306e61e2a870978
66ff364f0180971f8c0559506cce2511ec901ec8
8046 F20110221_AAAFKI rogers_j_Page_57thm.jpg
c674488ca0b1898afd993c9b336a9a97
646aec8193ecb429941556106bbe82aa05d2180a
33558 F20110221_AAAFFK rogers_j_Page_79.QC.jpg
b52a7aa2eb458dc4980009d027f8a63a
1d359d120dcb2be3ab610eb7a6e36077c5936e7a
49835 F20110221_AAAEYN rogers_j_Page_38.pro
a81bed03b38bdf552c3acabc0e3e9065
eddff898ee38dcba8050110aed283f65cd9af338
71065 F20110221_AAAFAN rogers_j_Page_10.jpg
4105b3b89e7cc00b0c60eb234f8719fc
4b110ead43f0b4143e1512d86f458d968b057adf
F20110221_AAAETQ rogers_j_Page_61.tif
4ba1a48e2813cbeaa2ba920c9ceca8e0
e17849a27e36ea73d1b72ab80955e1c9653dc074
6381 F20110221_AAAFKJ rogers_j_Page_58thm.jpg
5700c9dfa7f3449c95c779a466e587a8
843a836958d9416f7c94664cb7f2c9e3f5141381
96924 F20110221_AAAFFL rogers_j_Page_80.jpg
9c26c706ee458302372d8e57cce8e8b7
72404afaaedc057b19f05fc4188a85e3414fed4e
36147 F20110221_AAAEYO rogers_j_Page_40.pro
fca1ad319ac68518adfcc7ef5cd1b225
90f52897c81624a43c673fd9d9e00b2d8617e9c3
21246 F20110221_AAAFAO rogers_j_Page_10.QC.jpg
5e6701827db830cf81790fed5d6d154e
db8a0b80279f07601e16c8f5b476668da14ca3d5
F20110221_AAAETR rogers_j_Page_62.tif
aaf33a85075b0b0e489ca770db313068
94fb5a0d3d675c352491ab3b2f594fc08b616c96
7545 F20110221_AAAFKK rogers_j_Page_59thm.jpg
f2385113dfcd0440e7ea249b24d05cbb
8aee4dc37425debf26e65fb21d209e416318fe33
31356 F20110221_AAAFFM rogers_j_Page_80.QC.jpg
8ffd8097990fe68d2a5a9f2fe58fbd31
7f1c38fbc9ff6e5b993f239fe264d6e2402b8462
39183 F20110221_AAAEYP rogers_j_Page_42.pro
17de0b636dd59b37807ee460e9f21d2c
226605cfb2706d0819629bc295c029f156de3ffd
73171 F20110221_AAAFAP rogers_j_Page_11.jpg
82ff101463a41534643c475beb2de33f
ad2b426b3f0f28b7307e57ed24755a40aa4f3956
F20110221_AAAETS rogers_j_Page_63.tif
d6feeaecfd50b170595ee0d5b2662580
0a43dd6ac2dd9b7af89174527287728ea10faaa2
15689 F20110221_AAAFFN rogers_j_Page_81.jpg
2d1c4f6e862d7f0acdf315f18dd9d4c5
382b8c5b734dd649af0fdbf9e7aa02a006e3c037
42149 F20110221_AAAEYQ rogers_j_Page_45.pro
aefbe9e59712a6cbca5317a0bc7d14b0
32e65d259d88fc45c3479670a5b67265caa504cc
22178 F20110221_AAAFAQ rogers_j_Page_11.QC.jpg
170a312c7a75f8246cca76de0a2a49c2
21e6cd442d540dec51ad8b741bc1758738fab668
F20110221_AAAETT rogers_j_Page_64.tif
56146e36c1fa43c14e1862b093b0f1a9
66982549e31d6fcc3396bbdfdcf3ad31a2204aa6
7101 F20110221_AAAFKL rogers_j_Page_60thm.jpg
2f5c85b50387c8b54ec07b6f744bb02b
097815edd6e44b53317363df1175b2e9a1862536
5770 F20110221_AAAFFO rogers_j_Page_81.QC.jpg
59e836fbd5198c284bd630502474d178
ed800c323d1a3ce65ea0c241196b1f731179cef2
44902 F20110221_AAAEYR rogers_j_Page_46.pro
91669f2299f17427d9ae55208471948d
e05d6f66a6d16bc9d2b01569607035d3e3dd02ca
12748 F20110221_AAAFAR rogers_j_Page_12.jpg
9ec65874ec5eb56fd0b25e146f161c52
50a8d52171ad56b315b3d9780f99c60de2b36e8c
F20110221_AAAETU rogers_j_Page_65.tif
91f6fa14cf5d7add069297248d59603d
49a049c8503e95c4354b7760811f65283b659af6
8150 F20110221_AAAFKM rogers_j_Page_61thm.jpg
3e922c35c47189790bb0ed211e029bda
b047a4f158ebe6f675b67e3d99ab492305aace31
291442 F20110221_AAAFFP rogers_j_Page_01.jp2
eae9798015cf884f39ba8d38607912f4
a45e0c70f2040f2ed8c6f7a86af8fcefaf36c1b9
42307 F20110221_AAAEYS rogers_j_Page_47.pro
fe3fcfeb7376dcafb6e25d168e9080e2
b8c230593a5e073ffbfe6cedc4e542380175a245
4740 F20110221_AAAFAS rogers_j_Page_12.QC.jpg
c07d2f972084f1c7d41f1a0fc5780a77
0dddc71fbbe7cdbb981ae728f1d990909c58cec1
5706 F20110221_AAAFKN rogers_j_Page_62thm.jpg
9215180faf47106a0fe5f5ea78aafe08
6fd5416cc9f8efbe02ab264723ea4d69ae53a114
31430 F20110221_AAAFFQ rogers_j_Page_02.jp2
efc468e9fc98c907fcd14b8f1a0abe4f
7cacde2b9f10cd39ec584410b97203530da7b93f
44742 F20110221_AAAEYT rogers_j_Page_48.pro
9fa88e19fe659a6d78171bb50213a017
ea6837bce390ef1aeeb272b70a2feef5ca57a41c
89121 F20110221_AAAFAT rogers_j_Page_13.jpg
3bcbe4037e2c193ed8fb6130c63486d9
c25a28fa0a78d58abfa728621f6e9c590ca860b3
F20110221_AAAETV rogers_j_Page_66.tif
7a4c486de20a191759c9b2bd434ced91
0dfd514e8b066f2afec0f37723ad4327baced9ad
7016 F20110221_AAAFKO rogers_j_Page_64thm.jpg
5211964c1d7f0f3fdee79e20dcc2b3f6
f2c00cfc07019e5b585fea611537b557ec28c545
129829 F20110221_AAAFFR rogers_j_Page_04.jp2
84167f9e714db08e75eb7da017f47325
55ae5841ef8f5e07bfcbacd78faedf6c83f78941
47631 F20110221_AAAEYU rogers_j_Page_49.pro
8ebfa5e4398e1ffae757123053855f9d
17ebbcbdb23cb76fd66d709ac42fa090485fc85b
29211 F20110221_AAAFAU rogers_j_Page_13.QC.jpg
7e4c308ebd449ae1809ecbe3eb984f08
e639cc9465c6dc5528f0d6d8120004754fc612a0
F20110221_AAAETW rogers_j_Page_67.tif
30b15b805c85827d4c2c7cf0f120a7a3
2533da293cf3150a6e41399b5d8f25311455a4ce
6955 F20110221_AAAFKP rogers_j_Page_65thm.jpg
7326557cb0e1f6de6c97f6f0eedefc0a
31d40c98f6503f4c20de7fc4968165eea25eef59
983169 F20110221_AAAFFS rogers_j_Page_06.jp2
95843f3ab055279fecd52bf233d50865
5b31ff066088b3af8df7866e53e85b091021ff13
46864 F20110221_AAAEYV rogers_j_Page_50.pro
84f47bf4cfbe547674ba4856ace21d59
01e968b32514fc9114af3d66481e2e921bed0ead
24669 F20110221_AAAFAV rogers_j_Page_14.QC.jpg
3ace1d74cb59b1f8fd9cdb0474c402d6
0909a56aad567bd90332bd0f3ec7c8b263429de1
F20110221_AAAETX rogers_j_Page_68.tif
9b247b0d8c423d54a252100d348860e3
072d6e6225c8d6996ba52849444beb7e6f6c534e
7727 F20110221_AAAFKQ rogers_j_Page_67thm.jpg
ddc463880dccb9167219a0ad61d9d927
e6d4a690f88639703b7aa7a1d2cc9b750e0bb172
141723 F20110221_AAAFFT rogers_j_Page_07.jp2
425dd4bf67d4fa2d1e62babb0e7946fd
c654ac43d7aaac46066a6a86b40e9e0f48ef193b
40689 F20110221_AAAEYW rogers_j_Page_51.pro
2b2319cdbbc760a2441852b1bca2c015
91f8db7d4534a2e51966bf4e71c8d0e1a66950aa
80522 F20110221_AAAFAW rogers_j_Page_15.jpg
3fd2fa3039efd32721c2bdd8fe6527b5
25513ef78750012c2cce62546894b4a0cc3f15a9
771132 F20110221_AAAERA rogers_j_Page_05.jp2
cff77e6d4a4dde38a1112f35b7acbef2
f278eb6fd6df9a50940ab11779e54817b57e5766
F20110221_AAAETY rogers_j_Page_69.tif
6dc4a99b85d81400496d3f14eeb7025f
1dc35e8b42454413cb44872db1ddf9c8a37874df
8079 F20110221_AAAFKR rogers_j_Page_68thm.jpg
df4699e33c13425c769b522252d8eea7
6c951b57d40a28f7365f90ce97e5865d31b1e351
629072 F20110221_AAAFFU rogers_j_Page_08.jp2
3b4778b6a98273cce3e87b80807a8b7e
34e71d0d9a37687f3af877ef145cc81cf5a19751
49122 F20110221_AAAEYX rogers_j_Page_52.pro
379dcc8a243903a9a5936fbff8ba04c7
086aee284c6d9dee24bcad6eb1c0e3de8738d6af
27101 F20110221_AAAFAX rogers_j_Page_15.QC.jpg
b38527309e443e4ef78eb4ef15e5c4b2
ff819c937130abc3380b88f6889d5901f4352f65
8103 F20110221_AAAERB rogers_j_Page_79thm.jpg
7e6ed7c3b9bf4a11936f45b897a91bfd
ef08593867f32a44d55c4dfcaa9e49a342df3aa5
F20110221_AAAETZ rogers_j_Page_70.tif
fdcbbfd498216d53e215db1a26fddf43
9cf8a8cd3c2aa83c87ed9c92e36569810b1600f4
7957 F20110221_AAAFKS rogers_j_Page_69thm.jpg
70fd5e935f24ee5cd9c564513f942de9
35e98478ff89dc6947ff1d2f5802eced1076903c
831243 F20110221_AAAFFV rogers_j_Page_09.jp2
598c2dead904f97f920baff1bdf9699d
8fd80c20ebb5cce00d1bfdd39e736bd3dd412979
3169 F20110221_AAAEYY rogers_j_Page_53.pro
dcf672c0653c986731fde6f364a1354d
e42a88fb0a7871a4b071d59880aa9bb0f6f246c2
77327 F20110221_AAAFAY rogers_j_Page_16.jpg
dcd7902fe40277524aec5e4956ff08fb
c50a9b361031f85a9294fbb5dc57dd9315e191bd
973257 F20110221_AAAERC rogers_j_Page_54.jp2
aac4751b9d9fa5ad660567461d8f0898
1016069b3f641c90897614b3e5ca018375acee9c
7714 F20110221_AAAFKT rogers_j_Page_70thm.jpg
94d5a09a6b6a2fde76856ff3e392f7e5
21ce232a063fa38a1a4e7187014d4067f3bd2445
776172 F20110221_AAAFFW rogers_j_Page_11.jp2
c12e02a4d2afe3295ab04587945b482c
678e2df2d7963461d12d51b24980830f391ba43f
1688 F20110221_AAAEWA rogers_j_Page_47.txt
9c5142005fd5bcab2398e591dd4c3bb6
8972fe8771cb1e712ca0af2d85d692f88bd335c5
42081 F20110221_AAAEYZ rogers_j_Page_54.pro
e128fa6f522febeeeec5eeb13be95ba3
de945b1b3a514f1ed805491be44941515f9888b6
26021 F20110221_AAAFAZ rogers_j_Page_16.QC.jpg
25165a6fa68db31f579ec322ae61a2e3
e3a46b65de383f99f076450515f626d5fa636cdc
43756 F20110221_AAAERD rogers_j_Page_67.pro
30d7b554821f701e2889d296d5def06a
bd593f3daada57e40e3d9e1113cbf4de170a82e4
7395 F20110221_AAAFKU rogers_j_Page_71thm.jpg
88247a7645a5dbbcbd9cb4e306ce15d7
6b85e8e129737c83f5b7e3255a20546b865759f2
107966 F20110221_AAAFFX rogers_j_Page_12.jp2
3802efa3a697ae18d1aa414d2dd866ba
b0b103742211b0dfeaaa9b3276ae66b7204d93be
1893 F20110221_AAAEWB rogers_j_Page_49.txt
4e94eee78ba3956ca3ffe8e97e525000
af0e59ad24427017c044b52e9f1d077268984f34
46632 F20110221_AAAERE rogers_j_Page_44.pro
ecc802e180145804527d0ce07bac001c
e5f89e100316008daaaeb0d5b445f6c8c28a7e0d
6950 F20110221_AAAFKV rogers_j_Page_72thm.jpg
0cdf58eb8f7f0b8de33e3a929c24c3ef
246eae96d06f93ade0e964f0208c1f10f39751ff
971765 F20110221_AAAFFY rogers_j_Page_13.jp2
f09a44c180432d19711e310dd13b3461
4a667a8ba00c686f37dee733b787425c436d8c6d
1865 F20110221_AAAEWC rogers_j_Page_50.txt
6046a3f41deba322978e449cc680ba6b
041a7b91fea5300b39b3b5b300e4bb233ba2bce3
1033274 F20110221_AAAERF rogers_j_Page_35.jp2
b8969d2f19c561250cb0d180bfc9ddd9
075a42a13a8744bcf564561f4a0f0a2424c9a790
28962 F20110221_AAAFDA rogers_j_Page_47.QC.jpg
af823f2ebd67ff4610a128dfb612803b
da60d183fec1accfc9317f738982e19d52001704
7660 F20110221_AAAFKW rogers_j_Page_74thm.jpg
4602eac4e341a15996b39585dc45aa09
b8b3d42385f6555f49869718ef7f47eab689ecef
763398 F20110221_AAAFFZ rogers_j_Page_14.jp2
b3d29ce37f33eb997e88f60a681c0bbb
80abe0b44cccbe3f25da4fa81fa86d851636949a
91148 F20110221_AAAERG rogers_j_Page_28.jpg
fad9b180f6a6d8242f47f2c8bbdcc267
6cea2c7b963d012138d8a68839202ce22154a139
31091 F20110221_AAAFDB rogers_j_Page_48.QC.jpg
43225bdebcb7c6b7c9558a4d1a1d5116
d254502c01364ac0bbc35c226cb3105f91e2b5bd
1633 F20110221_AAAEWD rogers_j_Page_51.txt
5728f17e24d7554067aae6fc1ba2fbf3
5bca6c59b997e796ad8a7d9fb84377c37fee5f48
8679 F20110221_AAAFKX rogers_j_Page_75thm.jpg
e7155cc0beaa6a748421f67b5641428d
364f7f39d872697df4e5f87d0b8f70efc0dd7410
45336 F20110221_AAAERH rogers_j_Page_69.pro
f37f490c1cb5164aa649e31c88b5aef1
be948dad55dcbe2fa64b0bb4bf3600a4fbb20917
99739 F20110221_AAAFDC rogers_j_Page_49.jpg
8178ce4b94d29b5bb96e113e9f32912b
1a4432907fe6612ab6bfc631efac8aa26db7e968
1943 F20110221_AAAEWE rogers_j_Page_52.txt
fc0e02fc8d345fc3f5aa3326cd7be956
023d70e7e947384685e023a44aca0356b30431e7
7887 F20110221_AAAFKY rogers_j_Page_76thm.jpg
4b4c9703a0f3298c8605b64addb2fabf
4a6085abcbf617de2bd176fa6bb93b7cea8a68e4
977556 F20110221_AAAFIA rogers_j_Page_72.jp2
623a26707c2669adc73207eb28cb9320
7ec9df1654a3dc840562128250dfbadace0edd82
15182 F20110221_AAAERI rogers_j_Page_39.pro
26067e137c378858c43f10e4bc56a43a
164e2adfda55bfc871edff5e4c5e4c18f88bca00
33027 F20110221_AAAFDD rogers_j_Page_49.QC.jpg
24a0480fdba66fa4c63d707ac16595a4
2d9f94a41b6d6c5d32c6af09a6c3db3f7ab9416b
1747 F20110221_AAAEWF rogers_j_Page_54.txt
793adf517bc1fa7f09755cf7c7f7b8ca
c95abbaa7bec0d7dcbb4cff777e9b7a43b1ddc79
7983 F20110221_AAAFKZ rogers_j_Page_77thm.jpg
a4185296835c6a5fadc9a35a939bf04b
dd20b10f3a743dad51d5f3dbb0c387db5678a774
592368 F20110221_AAAFIB rogers_j_Page_73.jp2
2e647d4c30b19756b6ab642344baf84e
a936813a08cd4ea81bf28dbcd245024c3f2ad067
131835 F20110221_AAAERJ UFE0013389_00001.xml FULL
0c97622e590d4b234ff1455cabc23f41
2f716445a322622ae281120c92dee05a5e660c50
1948 F20110221_AAAEWG rogers_j_Page_55.txt
03d6468ed0aac107fe0b61b503fa1e58
979426f74d520391e5e7237b06bc3da7245b5cf8
1051948 F20110221_AAAFIC rogers_j_Page_74.jp2
5672c2050f64102232190fe6f85e662c
56649ae63dd7fb456eff811e165dc7524439e00a
100334 F20110221_AAAFDE rogers_j_Page_50.jpg
6a483f53af4bd557e6b45f673f974313
62c73a7120694088b4ce4da106d49c1c8d5f2585
1884 F20110221_AAAEWH rogers_j_Page_57.txt
f371cc9cbc837db61312889c19fe0239
34e5a2efc94222bfa0577ac4bebb412ea2d8bb54
1051944 F20110221_AAAFID rogers_j_Page_75.jp2
9f43fdb2ea5cd871a50cc731ee37270e
eb88d4381d64f275dacf3e87aa29168f4ff94576
35405 F20110221_AAAFDF rogers_j_Page_50.QC.jpg
4b190c72b08424f76b326120298eced9
3834fb3bbc325009c2a5b98b138fe25ae7049486
1565 F20110221_AAAEWI rogers_j_Page_58.txt
d26723c1b9ad0ebbbdc16bfcf777de6f
b4a99a75ee89093dfe41d2b37343f1c77a5be47a
F20110221_AAAFIE rogers_j_Page_76.jp2
870b4c2f097e060e65c2ea0e5990c274
ba0981aaf09b1a73c7832f7d45039a747f8dcf8d
F20110221_AAAERM rogers_j_Page_01.tif
c81e46519e79e8d18d71bfaeb4f2e422
41272bbc685bbaada13738cb383f8949eaccc864
88324 F20110221_AAAFDG rogers_j_Page_51.jpg
d00f119137935e7f067b45397fd546f1
738f5442ad45f0796752b0bf295423cbebb96f57
1799 F20110221_AAAEWJ rogers_j_Page_59.txt
a13853806f677e2534a380f17f0147f0
d1f1c0420ccb3ac8ee59517d610b0c157b2a52ab
1051960 F20110221_AAAFIF rogers_j_Page_78.jp2
9bb3e683a58481c38354a78609a98eed
e1d7ce33935695cc4fe2808b740a0d5b41413742
F20110221_AAAERN rogers_j_Page_02.tif
7c22ae74f86b6fe95da4466aba12e770
5842e7f2c2121eb4cd8fa3d99b231c23c01e59b8
31325 F20110221_AAAFDH rogers_j_Page_51.QC.jpg
9bb977eabbc82b40479e14c15994a3e6
1c55fb3100e42b4025fcd4a00ace042572f21d83
1727 F20110221_AAAEWK rogers_j_Page_60.txt
4961af0853a929961f274addc236f486
a7e5eed4fe0119299d33e6f042b2b8a4026f07c4
1037770 F20110221_AAAFIG rogers_j_Page_79.jp2
fb04323b05c82d3fd7e9c265e5b0dfb9
ae46a907a636352d8021cb18386dfff331dcde8d
F20110221_AAAERO rogers_j_Page_03.tif
b7dabf4814fa7f8793ab30ea03e40e12
f97a3a4dcf8bc557b6e661dc1880e8a0f9a33cfb
104515 F20110221_AAAFDI rogers_j_Page_52.jpg
2bfe1d324d8f44ca99efdce26dfe752e
5a203f79f8ef6f28d21eb28e4342206f0544a090
1668 F20110221_AAAEWL rogers_j_Page_63.txt
205930b2fb162ca270bae644bcdfc52d
f3a9e30dfe525368e1fc7cb7eb66456cdb295b4a
1034876 F20110221_AAAFIH rogers_j_Page_80.jp2
7924704616332ec421612aa0f6feb3a7
8d5b0f8ea922aa38069044b900a38f0295fad916
F20110221_AAAERP rogers_j_Page_04.tif
74e0f443a7ff4b48f5b30b6072c303b9
2d499177854363da7b7e0c3c5674b65bce1eb97d
36157 F20110221_AAAFDJ rogers_j_Page_52.QC.jpg
75bfa1e7a4810cc3953aec6afc279a7c
f6b50eb9eddc40378385e79e439c800f9962ca67
1703 F20110221_AAAEWM rogers_j_Page_64.txt
daced09563dbd1aa53273526cc48bd7a
d50441b18ae866a1a4c8bd27656d172f02e776a4
141161 F20110221_AAAFII rogers_j_Page_81.jp2
0da62011d9164ed4fd6b1601c6260984
3b67d726d1615115f640f3bf94fb91da760c6947
F20110221_AAAERQ rogers_j_Page_05.tif
a47e83d9f3047b81b57d88019ac30040
eb236542b76da5c4d75a53020f646e50d3fcebe1
8869 F20110221_AAAFDK rogers_j_Page_53.jpg
804fb77760c6a7dadd7608f30a1a1ee5
2674f36171e3c4bec29f8a907e923f10bed5dc74
F20110221_AAAEWN rogers_j_Page_65.txt
a25ec1ab658acc56924e428a2fb78ad2
c3f0b23a76236845b3ee122981358c38aaf4f7b0
F20110221_AAAERR rogers_j_Page_06.tif
9c184852cf8b853d7fad8d140771414c
2c8951be6e1bf3fcc40234ed1d497fe7b917227c
3534 F20110221_AAAFDL rogers_j_Page_53.QC.jpg
1c947c54481640f38a8cc301311f5fdb
13d3042254ba7d1fe6c7cb3f94522204f55399b1
1770 F20110221_AAAEWO rogers_j_Page_66.txt
04827d4d0f5e62f2a7368b64ab0a3ea3
1b465e2d086e39762e1f955e34cdfcaf512afadf
2450 F20110221_AAAFIJ rogers_j_Page_01thm.jpg
d0a6d447e9bf1852be60bb69f4b9013d
bf0aa7864c4f0aaf9625a659cce0e837ece8c1c9
F20110221_AAAERS rogers_j_Page_07.tif
b7c3570007c196f2ea357c6fd0ce8e45
e79598abbc5eaf4e55f4c3fb4c9824e366b471e9
89759 F20110221_AAAFDM rogers_j_Page_54.jpg
830f49f5277ed758b84e7ed9673aa4bc
784cdc59083e8163ea75f7e90989e50b1860a0e7
2038 F20110221_AAAEWP rogers_j_Page_67.txt
87788fd66b3c5bdc8b7eaecf7d1b50f5
90e05442f2df294835f40c35264c8f164262dea6
637 F20110221_AAAFIK rogers_j_Page_02thm.jpg
2904b5ca85b92f076012dec48d8f6abd
e3c84238dca76ced37e7f5e5a6099028936928ea
28817 F20110221_AAAFDN rogers_j_Page_54.QC.jpg
49907e7c330a2194df3766838a3aa38d
b83675f3dd48ab889d593807f6ddc30bff1dfe49
1873 F20110221_AAAEWQ rogers_j_Page_68.txt
f59de9485cb4eeedd70eba25c246930c
76dbfe654324c388c7d235330760823dbbb8566c
1440 F20110221_AAAFIL rogers_j_Page_04thm.jpg
94f89f7f1ae38147621ceb073e6383d2
dcc7071f199b95eb2e7e61da9ae43fd8d67d864f
F20110221_AAAERT rogers_j_Page_08.tif
fa035f54fd1a990af062f7017674d27a
efe7f8ea1793df66a2ed817236ce17d681e7353a
78493 F20110221_AAAFDO rogers_j_Page_55.jpg
1e15fc9e37e1386b180f697e88c0ca04
afed790efbfe94a8dc41ef80338575225f85a996
1811 F20110221_AAAEWR rogers_j_Page_69.txt
a9a22dfe0fa3968c73ae9c09a5964156
e994867bc811b0a9cc10b57fbe33120ac5ba3e94
4903 F20110221_AAAFIM rogers_j_Page_05thm.jpg
5e4448357c339df38b4ad218b0c7c5e1
bfb376ad476a686315372f4106fa53ea2cfe54a9
F20110221_AAAERU rogers_j_Page_09.tif
98ed86808e17c6dc5ada196585224a7f
380d5c2cecea413b738f77c676b2ff2f3502120e
26399 F20110221_AAAFDP rogers_j_Page_55.QC.jpg
c4cf198697e64055a46612cbd03f3995
a3132cee081103506d0ec8e32f41ab2a3f5707de
1740 F20110221_AAAEWS rogers_j_Page_70.txt
4cbb71fa056edbcb3fd64ca272acce09
1beb80ef3e5e916bf0f127995cf79e178e1ceaeb
5625 F20110221_AAAFIN rogers_j_Page_06thm.jpg
d11a47035761fefb03e6343025a84a31
7399bc360c30ede0ba4146cb82b280619459d3b9
F20110221_AAAERV rogers_j_Page_10.tif
6f6fae694d4f9476ae4334792e885e25
4754bc583c14b0c8ad04a55db9b885d94e05c8d8
84225 F20110221_AAAFDQ rogers_j_Page_56.jpg
a479638677e17e667c6b9bafa4b8256e
95bb4d37f254874f41edc8c43d821a5be8fd9346
1701 F20110221_AAAEWT rogers_j_Page_71.txt
29bd522300a5c5b5b9d8ebc128fd7f7e
bbd5ea750adec13953788367518728b9be160e94
4730 F20110221_AAAFIO rogers_j_Page_08thm.jpg
68f85b8db5a696ffe5fc3eb0c318a8b4
c89226514f4d34aff5966bd8c7495187077c0140
F20110221_AAAERW rogers_j_Page_11.tif
2d3fcc3baf72c0ddb8b984f337557d4d
d96b784e2598a5782bbed573dd1f6d72700fdf08
29286 F20110221_AAAFDR rogers_j_Page_56.QC.jpg
893d13424d2f6429359964621d6b0140
36afe61fff40c7d0fc8bde21da86a38dc084b94f
1797 F20110221_AAAEWU rogers_j_Page_72.txt
da6103d0b8f7daab8f63ccc152ddfc13
1913b84f4b15c17dd979d502155b69cae2747252
5850 F20110221_AAAFIP rogers_j_Page_09thm.jpg
77f9c62c67cde4f1e6e8806082fcc489
3c1bac292a6179df50c2f2102bdb9ee447eacf2c
F20110221_AAAERX rogers_j_Page_12.tif
333b3b76d17d38aa2bb3f15a4dc80abd
d4c929c20c134c047fe6afdb270617ab8378365e
100023 F20110221_AAAFDS rogers_j_Page_57.jpg
f051f071e9a09d37bc19ce35cff2b578
eb8ef4b0c945d109a77e6735f89e89d31cb8ab61
1020 F20110221_AAAEWV rogers_j_Page_73.txt
828e1eea112624a1faaca88ea48f03cd
9f7b978e16f9c30b1b7deeb897ea5d692a0d11e2
5300 F20110221_AAAFIQ rogers_j_Page_10thm.jpg
cc2bd186a08e4569e2e11a2071d77bc1
7b423b496aefd8b59e1d8140744f192a4ce0b219
F20110221_AAAERY rogers_j_Page_13.tif
7a18498f0010de2bf001b890d9381720
23dce5df6ebcf746d3c10f438588504309ea2a9b
31745 F20110221_AAAFDT rogers_j_Page_57.QC.jpg
5cc77eebf6684dc43b86390a46a8e840
ac4eb69b03ba3463759d02f85db8df7e6c728893
2200 F20110221_AAAEWW rogers_j_Page_74.txt
b297aa9754487f5e46ace54f6afd26ea
82471ce0f59283cbbec80e4c06e99bd6c6dec2dd
5904 F20110221_AAAFIR rogers_j_Page_11thm.jpg
cdf971ec881d96c17fc5edd7d55ce829
64971fe8b7bdd49d085e16be588ee348b563a2fe
F20110221_AAAERZ rogers_j_Page_14.tif
375bbaaf1e8868eb1a7622821ccc3289
866db7870896f0e0e6dacef94e577f6f4ce79695
71533 F20110221_AAAFDU rogers_j_Page_58.jpg
8064c86dec78573d02208eb9a3ea53c0
71dd0a2b6f8ae42f2440dccb0d3120bfb8f31638
2203 F20110221_AAAEWX rogers_j_Page_75.txt
128e71a90ea8cc52312b60fce693a4fd
8efea19eb37274b9d3cc79036655427195110f26
7008 F20110221_AAAFIS rogers_j_Page_13thm.jpg
8675d7cf6853b74b59e1deb15fec2c73
485dd2edafe1c208000df486c3cb81ad069d505c
24163 F20110221_AAAFDV rogers_j_Page_58.QC.jpg
e18682fbd3e810a6ccab1fb51d81eab5
1dde6027255be875ede396c65d70447207f6ef40
7017 F20110221_AAAFIT rogers_j_Page_15thm.jpg
f132a311893913781e6a5b436705e453
e393022e3a646efeac7bd03aed0dcbb9374cd6f5
90796 F20110221_AAAFDW rogers_j_Page_59.jpg
b350945788d2bf8b85639f626f352c60
70e93058b38fdcc4607ebe0ab1a248ceb9161c87
F20110221_AAAEUA rogers_j_Page_71.tif
cc75c1648bffbcd75802e685ac628c76
a4c2010898f24263410f33a6ae42af8db5091a9c
2231 F20110221_AAAEWY rogers_j_Page_77.txt
1433c9702285996c7bc08192f8f68ab9
901ec05484df3e99e585696162f9487b43587127
7372 F20110221_AAAFIU rogers_j_Page_16thm.jpg
aed87d30f400a815956a5dbed2e1a89d
5af7b789f340cd0541d624061267d63554fe5899
30178 F20110221_AAAFDX rogers_j_Page_59.QC.jpg
82325440ea58c553d607f2e8cfaf0fd9
6a1a73716b21122da8bc4ddc33d6f33c111d938a
F20110221_AAAEUB rogers_j_Page_72.tif
95c101e6bfc57d6e1cfffbc84570a461
f9ee3b6b2907967f3aa6e6ff0800abb6cd9f1ee0
2425 F20110221_AAAEWZ rogers_j_Page_78.txt
b147330fcb922c9b48a92b8b76628a1b
a33deaff6604c759e7ab24702bb51d68edc41a6f
5889 F20110221_AAAFIV rogers_j_Page_17thm.jpg
f7cb6873051e494ae6033023cce17fa9
8aa2cabd7c40eb97b11c36284ac8839953d1940b
64211 F20110221_AAAFBA rogers_j_Page_17.jpg
c33b85e2b3b6e420e0b195b55410867f
873421ddea58b34987200bbec9e3ce82db1632ce
79387 F20110221_AAAFDY rogers_j_Page_60.jpg
6b0c9e4cbfd2646168d57698c49e848b
fe2e63a65538e304106bbccb8363eb818d9c9c1e
F20110221_AAAEUC rogers_j_Page_73.tif
72bbab4b329d18382f91997c7dc72b31
4856b6da78f899e88bb88e9a8806382d709b950d
2112 F20110221_AAAEPF rogers_j_Page_61.txt
37fc8e0629e83d743f87eb8fcb0dd79b
dc842ebc57f531dd35fe0e02190f5a42d97d61b7
6978 F20110221_AAAFIW rogers_j_Page_18thm.jpg
d1a5fe43baf2d8890a964be9aadabb3f
c1ffb571e09fd5c43513ea825743631e323360e0
21406 F20110221_AAAFBB rogers_j_Page_17.QC.jpg
65a3ee2065640bcafffa10c28f9c76df
8ae8f7c80299b47cb5ffdf5cd84b90dbd38a0ee7
26589 F20110221_AAAFDZ rogers_j_Page_60.QC.jpg
decab59e4294a8ccd99c14a1720d2556
27cc79e0f4bc43693686a7823be5ed7995582b23
F20110221_AAAEUD rogers_j_Page_74.tif
42d27e51b1be288b5cdd848fa418cc4c
a8797283f55f5a642ef23e30c07410f9f933c6bf
F20110221_AAAEPG rogers_j_Page_19.tif
c21ac77b316600abf580906f34b7267f
7aebd11714477b69f586bfb17207126822a78229
39813 F20110221_AAAEZA rogers_j_Page_55.pro
bec91234c8cf4832dbb2684f0dd808dd
5e1e0ac98c4b71ad89afcef002d5b5c8dea663e6
7926 F20110221_AAAFIX rogers_j_Page_19thm.jpg
e2a08ae75a388a26e77d28976a9100ba
7d3582dcee7afec9541a71294beac04e446f8176
F20110221_AAAEUE rogers_j_Page_75.tif
60539d71e0d7ec9c3328ba382c89d1bb
30eca2dc500c365d3acf0fa61ddda7da79b282d3
7654 F20110221_AAAEPH rogers_j_Page_03thm.jpg
77596ec8957f2676ed915f10580698e9
8ec2796868426c707e5dbfb1656b387bfac54b48
47701 F20110221_AAAEZB rogers_j_Page_57.pro
5d3ba091d61e504b5871e91174d7fc1a
c391d690f751948d73bdb9bc6d229e4f610e36f7
7206 F20110221_AAAFIY rogers_j_Page_20thm.jpg
6fa6b08416c598f7e2825cc3280a6fe8
90f9b3cbcc99bf2f8714596156ed076182bca3fc
829470 F20110221_AAAFGA rogers_j_Page_15.jp2
1125e5b6025205727427776464d73bf6
0818f781c7de6891ab05a68cf784502038861c0c
83248 F20110221_AAAFBC rogers_j_Page_18.jpg
0cd9dfe91ffdb5c7322b17c6aa997342
7b91c49e047201c4c25d37b20fe4e1f22a4ceddb
F20110221_AAAEUF rogers_j_Page_76.tif
4f5e6d9cf9932c55f9d9766dc2c3d3f3
d94ffb638458031c1807c0bebecceb605a439081
865552 F20110221_AAAEPI rogers_j_Page_51.jp2
52cb10084b69a734f1424e2eef8ab2a9
21c66b4de49a93b72030f57ef603853a2510130b
33824 F20110221_AAAEZC rogers_j_Page_58.pro
7b18e21fb8df2f99980eb93a8733aeb1
7c8375dd4ad91f0b1695aea8055d94f860fc2a6e
7220 F20110221_AAAFIZ rogers_j_Page_21thm.jpg
6c7280f55ea040e37d952b83ce388ede
49a2409278c705c036e27cea8ecb4d5acc2eb7ad
774143 F20110221_AAAFGB rogers_j_Page_16.jp2
1ae00a04457c584561b01ee5f43b75f6
6e7238bf131edcd8f73cc66d6035fcb99098f6c9
27744 F20110221_AAAFBD rogers_j_Page_18.QC.jpg
85c2f5488233cd7f24d9fa256abd3843
1e3fe943ad7ec63ab348277eebd42c0fee9bf62f
F20110221_AAAEUG rogers_j_Page_77.tif
ccff43b78991005520e784ce11bbbd80
56b1c5a91566336fa0b923f9ae2caa3a01a84416
1291 F20110221_AAAEPJ rogers_j_Page_12thm.jpg
ed02c9af4ded5aba6e8e2fc43e41ed11
71a8855abe1e215ac43a5ebf0e3c9ee812ee79dc
42966 F20110221_AAAEZD rogers_j_Page_59.pro
0131741571486c19ad8cc62af12247d5
dd0b27dcc9898cc268edf97deae9a1ecce92a04f
651802 F20110221_AAAFGC rogers_j_Page_17.jp2
a7160df1f47dca379d554ff6187188e5
bedc8db34afe2bb73fe5f4c7b4d2830e369c5732
95226 F20110221_AAAFBE rogers_j_Page_19.jpg
669e93e85defdb8a7d47b01bb6957f6a
efe3f07496c770b2e085ce7f019f1790509f2e14
F20110221_AAAEUH rogers_j_Page_78.tif
63bc850d2f44f5870cc0a74a59dbd046
7bf1a0443cb4324ea923798d42049d8e05c17e80
1051986 F20110221_AAAEPK rogers_j_Page_77.jp2
174f8967b0cc68013fd2e27f00744ebb
92d85d25b6b02632a4f8510a975d537dc9d3a387
36357 F20110221_AAAEZE rogers_j_Page_60.pro
ac4df5e9200cd07c948444a35af8a871
0d3109652acb76d8b5f608db1e1387e821bc39ab
8807 F20110221_AAAFLA rogers_j_Page_78thm.jpg
f0e6ef098d27f261188474e37c321d70
b815975c69c577da356c9716779df19bd2495a2d
910151 F20110221_AAAFGD rogers_j_Page_18.jp2
aa24cc2362ab2cad73a40140dac2bdb6
258d072c5e8bc59309494bcc7c0cd91edbf8f7ce
30823 F20110221_AAAFBF rogers_j_Page_19.QC.jpg
86724e0f8dfbf527b5f342a144fdef52
8be5708a7f4228654c8f1078ca739eba774a5c48
F20110221_AAAEUI rogers_j_Page_79.tif
33354fc5fc75ba7a479de7538b8dd8e2
13b9f01337e6b4f4e46909cd40182909ad60e708
4395 F20110221_AAAEPL rogers_j_Page_73thm.jpg
d93e47b10ec07eeda995d5a8152d2fc6
c34438d90e0a68e3c7836a996e7acdaf4cca6951
46910 F20110221_AAAEZF rogers_j_Page_61.pro
022e45fcdb268abaf77bd5a179f4a518
fba859a6a0241a94a2bd2608d7f59e158b99b651
7841 F20110221_AAAFLB rogers_j_Page_80thm.jpg
78003ff007cc175ce33196fef8d9961a
c391b325f9da983fbe48076e511013c12bd91a52
1006572 F20110221_AAAFGE rogers_j_Page_19.jp2
4d18b9903637739c38067fb39adb7dbb
4581106efe26ac827653a536820bfa0343d30ddd
F20110221_AAAEUJ rogers_j_Page_80.tif
3d3c50fb158c5a6885cedeecee12a9c4
1be0ebb863604988ef1d1c8aae435c152b235639
6389 F20110221_AAAEPM rogers_j_Page_14thm.jpg
c3fa4241ceebdd66c98b3fb20e24388a
8507958bb3710075671baab978646e777acd398a
23481 F20110221_AAAEZG rogers_j_Page_62.pro
a7d6a5b3b48fd13da3c8389d99d873af
830ad63c909c9e5f851f7d9d30699b06e6a65547
80046 F20110221_AAAFBG rogers_j_Page_20.jpg
6e24c7857adc5c85c19eb3f6fac49b27
afd3f99decd552ada73e98fb532e55840beaf1d4
1590 F20110221_AAAFLC rogers_j_Page_81thm.jpg
91f15e87a2fb64056b93b76b5e036c6d
62cafdc826a16e92cd1ed9fd5c62dd6644deb143
822102 F20110221_AAAFGF rogers_j_Page_20.jp2
3ec9ed42410f540a06ef0e1c4ac55954
1704cc093c2227ba5a0ab1c11f9699c1ad1b0623
F20110221_AAAEUK rogers_j_Page_81.tif
713cd1fc42210b4d1401e99e031cc36c
552db3a195036668e3c38299c3f0e06149be453f
975635 F20110221_AAAEPN rogers_j_Page_29.jp2
454ca2aeae1e708f6ae1001d38cc2cf2
56eb45bc3c73c8051347e492107f9e02d6d4ea4b
22869 F20110221_AAAEZH rogers_j_Page_63.pro
5bf94956ed7593df2600a4083ed76403
8536c839020608e192241369a2de0084a54ee113
26926 F20110221_AAAFBH rogers_j_Page_20.QC.jpg
1fce7a9fcc86f8763623851c9fdafa36
2cf00b1e4e16d5df2242152ad564939283a854bb
464821 F20110221_AAAFLD rogers_j.pdf
26c646e6a458e821800c2db0650887cb
57c8a3124d5c46e713795f5a274d5e923df6fe7c
849492 F20110221_AAAFGG rogers_j_Page_21.jp2
41edf1342d75d2242155c9863a7bab1e
f1d77fe9075ca73a1e33bebc43f305a8cd82ada2
525 F20110221_AAAEUL rogers_j_Page_01.txt
7f2162e54c614339c1b5c30c238ee09d
43caf7f492d24797dbb5ae6e5a5fe7bfeee26ed8
39661 F20110221_AAAEPO rogers_j_Page_56.pro
df9e1a8d3610e861363ee35d5b90b345
a3c57af60720fedf7339b9cb74aca94ebe039e55
40330 F20110221_AAAEZI rogers_j_Page_64.pro
a5b783c767da42d9b7d9d59a82e3f289
493b72894d5bf1579d29acc75c199bf539d52425
78651 F20110221_AAAFBI rogers_j_Page_21.jpg
283e54d79185dd6274c9a1b8aabda582
58f45238c0cb6d864288e57cb1a1dccc3a7f48c8
96973 F20110221_AAAFLE UFE0013389_00001.mets
6a420f6c88b63c0ae7be0919cd4216b2
909dbbabec861387f895dca57ebb2ef9c68ea853
120 F20110221_AAAEUM rogers_j_Page_02.txt
ba60eb6cb9ef56a0ba1da7ef4f68d3f1
03f8e69577ef1a6e7a5c488c3463c35e2bae55ca
2055 F20110221_AAAEPP rogers_j_Page_32.txt
e47c5168a43cc793a8851b3becf00771
5297678d8c37ebb78d706284f14cc7d888f4a4e4
39211 F20110221_AAAEZJ rogers_j_Page_65.pro
7a5016de0f7a5d7360668e0c5daee131
50f42f40ea659c6f41a2ba544cf7f09142c9e156
26760 F20110221_AAAFBJ rogers_j_Page_21.QC.jpg
c8c915e89f122092d2b2d6ff2fdb92e0
1ee70e41854b4abab36836d0a33c67f6e6ca1057
695344 F20110221_AAAFGH rogers_j_Page_22.jp2
1402493760dc8f020417fb6507d566eb
40616a852e303b7ff5925b21ece63aaf2349bea6
1827 F20110221_AAAEUN rogers_j_Page_03.txt
c172438ab8eb6c573a6bbca8e0a4a0d3
8eb5d4a02554d1d99c7d62a6e72fd24055a0dda2
7454 F20110221_AAAEPQ rogers_j_Page_66thm.jpg
dac04da74bbe43190f9a93861fe5cc7c
985e2df571e533e9d89465782c3c7acaaf9a9906
41856 F20110221_AAAEZK rogers_j_Page_66.pro
515b7a3b790f3f32842a53415d5bbe6b
bfe25bd786ce3a6237b2d0acaa6ee8a080367d1f
68036 F20110221_AAAFBK rogers_j_Page_22.jpg
3e03ba678b4e41c4aa60191161b7446c
79f1f0cd0768dd68b7f466de8b6001e9f647e6be
981259 F20110221_AAAFGI rogers_j_Page_23.jp2
013ccda65627dc7f53b594398e030410
2ca2b5a130ebea82b575a93926065f7a39b54802
2819 F20110221_AAAEUO rogers_j_Page_05.txt
efbaba4b3c9d43dcd082fcb20eb5ff59
aa71178c76fb562eeda0975d39585975ce7b171d
46844 F20110221_AAAEZL rogers_j_Page_68.pro
aea0a1a07c2a65b482941c1c14986678
f992282fd92bb7e12dda4086a686b65c3ecd3cc9
23809 F20110221_AAAFBL rogers_j_Page_22.QC.jpg
4780dc6983ba46cb2540fdf2a6db0dc9
c8b42c97d974d54d5de56814b54c5f06f9d3c224
896319 F20110221_AAAFGJ rogers_j_Page_24.jp2
2e7886917bf259b07127ab77c2e68158
1aa11f07ba5f93be5da6a784c4c3efd150174a4d
3066 F20110221_AAAEUP rogers_j_Page_06.txt
0751e9bd0c6f2659ec698732efd2ac34
2568b938d9d932579b41b2becc5ba12dda80812e
33124 F20110221_AAAEPR rogers_j_Page_37.QC.jpg
6a87fbae983192a5afee1415dec6e61c
8e2a4167e25da59ccd65e3851c8bff9613b41108
42984 F20110221_AAAEZM rogers_j_Page_70.pro
d93b5753fd100afa25e5d19a3c69bb9a
45ef04fb3a37d1e04e9f5e63217a09b4b566186f
94014 F20110221_AAAFBM rogers_j_Page_23.jpg
2967be36b6e0d4684434986dbbc28774
490e83bf9822bbac4eb9932f3511f98d513c5758
816698 F20110221_AAAFGK rogers_j_Page_25.jp2
b9fdb5408d0d9d692f289af03bfbebf1
cf1f3cf6caa960d751ca55de1fb75f335de4ff7e
457 F20110221_AAAEUQ rogers_j_Page_07.txt
08643a8b3a65370c290b99e94c96925e
40c694fd8134db583a6eb0398ac90cc59cc6e44a
6371 F20110221_AAAEPS rogers_j_Page_63thm.jpg
c7839041b7227d0b4b0cb41dbcea42eb
b7b88e0d8e81258f776313e8a9649ad68400bd85
42439 F20110221_AAAEZN rogers_j_Page_71.pro
36dcb44c0821f55fa1aa25215369e5c5
9e57ccc2d6929e02b77b9dd16b90931f342554cc
30567 F20110221_AAAFBN rogers_j_Page_23.QC.jpg
fb294b4c31e99488f7778ba4b9db4c75
3fa44819ef4caca6f7d64ae3a1497bc34f86c7f4
850274 F20110221_AAAFGL rogers_j_Page_26.jp2
a3ddf41c686e425bcde57dc9c40cba05
32d17f1117cb518de9b1d9716277de960385ff95
1925 F20110221_AAAEUR rogers_j_Page_08.txt
a79156e30e3549c322c551303338c7c5
8d040b6bae85eb89e5e131597dccaae76320d2a8
54406 F20110221_AAAEPT rogers_j_Page_77.pro
85314fee8175ef436783acd10bae6695
34284ded227e786e9c77b2ebd4ab35fdb96edc96
43602 F20110221_AAAEZO rogers_j_Page_72.pro
a772f2b81b19b04dfc2e22d3d46dd781
b891fc13e592059ca045ab77efbb82570218534c
77952 F20110221_AAAFBO rogers_j_Page_25.jpg
cd635cddf918324dbf315f508504af46
30bd35b698c87290774ad6c5edf306dbcbd2a676
692923 F20110221_AAAFGM rogers_j_Page_27.jp2
36c3c1909bb13934cb644051431b633e
b5877c3522263b46bd768745630a5fbd4b337bcf
2161 F20110221_AAAEUS rogers_j_Page_09.txt
8532a15bca15dba339db95aba6807f0e
81e455ab868a337476acfd868d28a145247b43e8
2181 F20110221_AAAEPU rogers_j_Page_23.txt
4c268c60fc16882f18284933e7b0c14a
a0230479bf1b1bcc6669dacb533b371b98278f66
25516 F20110221_AAAEZP rogers_j_Page_73.pro
c381502d2d378edc9d09d9e24a449927
8dd09799732e7816548b29532734f1ecbf444eb9
25783 F20110221_AAAFBP rogers_j_Page_25.QC.jpg
3de0ffea267b6e8bd9b92969a8e8a35d
3c30f8e2ce15437e75263a2869d965c6f06dfa40
953075 F20110221_AAAFGN rogers_j_Page_28.jp2
bfb805fcb5344654b893cb68aa3af199
15e206313df390122ea900f057da096b68294e54
1997 F20110221_AAAEUT rogers_j_Page_10.txt
669208fb1975ee0cf1c93b64966bb2ca
736e276695193948e1301ab6837cabdad402a02d
65485 F20110221_AAAEPV rogers_j_Page_27.jpg
82bae06dcb1f7b8644d90c048d1c356b
218d3f2ac03ff34c3f0a5fbc51b5e70d6bcc7dc6
53275 F20110221_AAAEZQ rogers_j_Page_74.pro
465a111866690223bed5af9d5478b740
ceb8a8d98b0973c025804cd4c646c462aa02512b
78937 F20110221_AAAFBQ rogers_j_Page_26.jpg
1868ff5cdd22ecaf86617eacb8ed3141
bd6b87584ed4b42f1031ae1961162bd029805c51
1051932 F20110221_AAAFGO rogers_j_Page_30.jp2
745cb90fbf8a427cabd1ec306cfdf515
8a3b763c265c3805d60dbe4e2bd30a61f069dfbd
1509 F20110221_AAAEUU rogers_j_Page_11.txt
0290756196ab5fc97acde363ab2a00b0
8bd73fc09f46955d0208b3035cc8a1661833313e
1002692 F20110221_AAAEPW rogers_j_Page_03.jp2
d68f8ff14d65bf88278667c410344bdd
a2f5b049d12dd3d887951bcd3376055f32f3db96
54114 F20110221_AAAEZR rogers_j_Page_75.pro
84487152ed5e41f91818ab769c66ade6
8ae95351ae9d5bf335799f95afcbeccee5b0a048
26425 F20110221_AAAFBR rogers_j_Page_26.QC.jpg
32424537e2e717634faddc23e7c06466
e58521ea9f713ae0e463001a47f5b41f645e7d99
862386 F20110221_AAAFGP rogers_j_Page_31.jp2
f785f7ba86f696bb7813f4c0d153f05f
12d0d40b366ed53eef91c83cf90f5e2cdc1d473c
191 F20110221_AAAEUV rogers_j_Page_12.txt
e3b2a7258cae6fcc655954cc36ae23f8
b1c9cf546ec251cfbdd3ba678476d7e568acefbc
6454 F20110221_AAAEPX rogers_j_Page_22thm.jpg
4757572d94a2a03b5b916e4ba16aa214
eb3c6c0127d6e6ce34c54fcb5ce3c15bdc2c5c3e
48798 F20110221_AAAEZS rogers_j_Page_76.pro
459b377f3d34c7390190d6890bbb1689
ed541a8555f0ccf71f9b83d2994f36c51780082d
21570 F20110221_AAAFBS rogers_j_Page_27.QC.jpg
082477f07e3f8e18c49a9bf9ca6793c4
08ea9b60ab427c6e2e862b6f049ed38167a0cee0
887509 F20110221_AAAFGQ rogers_j_Page_32.jp2
5f12646a4d03074ecdf9a17060aea792
dfa5712bb80f5111f50c4911a0800dddb44bc718
91510 F20110221_AAAEPY rogers_j_Page_47.jpg
7fa998b2036a659299c4e77eb2b0881e
9627e2f21d799de4d0b960574670e8a35b7469f2
59299 F20110221_AAAEZT rogers_j_Page_78.pro
fe4b243c5b1ca5b4237ac499618cfb2f
631b3fcdeb40fa525c185764c6369a3ad0d68930
30454 F20110221_AAAFBT rogers_j_Page_28.QC.jpg
437910f4870aead195195602e5df95e2
67d0b955b2dac4b1b8e146a28f129f1a9f6fb07f
690771 F20110221_AAAFGR rogers_j_Page_33.jp2
f9c74dbd3bd22f092ed98bed79ecb4ab
b4ef2ed704d45a1882d04fd31e1667f1d6eb745f
1808 F20110221_AAAEUW rogers_j_Page_13.txt
33c5083075ce24403575a167245adbcc
e9085be3cabc0c901919aa46df895a7076caca2c
1735 F20110221_AAAEPZ rogers_j_Page_56.txt
e760a88c5767aff03628410c3171b934
018067521eebdd9c4f86e7317ea20005793a468b
47880 F20110221_AAAEZU rogers_j_Page_79.pro
9ac068d13c2a913cd17b41cc7f67feb6
7114c1581cf7f0a8120bf22aad760d9794570493
91772 F20110221_AAAFBU rogers_j_Page_29.jpg
27d4743143a6de7ef7707bfd54fba29a
b155985c6f49ebe4b7b0818989e2da97145b2f14
1017470 F20110221_AAAFGS rogers_j_Page_34.jp2
1cd0c49614c2f7021dfbd94ee5626b27
f477cf3f9dfb035c3bd28c8d295882374bff0c6f
1713 F20110221_AAAEUX rogers_j_Page_14.txt
fc38334a9de17b6bfe0164ba65c3555c
d956efce06cf99964c970e42c55e4ef46971dc66
46543 F20110221_AAAEZV rogers_j_Page_80.pro
206ed3602e06f67040570584beeeabf3
e65b7114ee46faf2be358d9c941618f187ed3315
29614 F20110221_AAAFBV rogers_j_Page_29.QC.jpg
2ca8efb68e4ca2b8b2efb66f9dc23934
a975b7001360dcf0af9c004c4403fc46ccc329a9
1026614 F20110221_AAAFGT rogers_j_Page_36.jp2
0360be5844209fdda7ab3fefd98a1a2e
3a62d3736ec984787134363c450d756b355c1bea
2206 F20110221_AAAEUY rogers_j_Page_15.txt
7c631dda17c918a7b2b1b523f8c0ccfb
be3cec5aed2b70d59a4c0bd3033d674a385fed16
30112 F20110221_AAAEZW rogers_j_Page_01.jpg
db46d7a375b28bd59493a240a5fb5055
7fdc2584e676ef18d1e7ba505ed5795063e48703
101294 F20110221_AAAFBW rogers_j_Page_30.jpg
b48fc1bbfd831f451a0016501d913804
a2d72abb8247db757b68186694c25ee59f941160
F20110221_AAAESA rogers_j_Page_15.tif
63d42afdcafe961a194529545b6f6f14
9c6785ce6e9172a708e3d3d231e25e43b326d8bf
966523 F20110221_AAAFGU rogers_j_Page_37.jp2
a949086562d9df2e683c9ca0f97c8ffa
3ac408eccbbb640bd1da5aa6db8a7e96453c6d0b
1783 F20110221_AAAEUZ rogers_j_Page_16.txt
bd122559a12d871d36c8eea19264c4a0
532d40b675a5ef711c6d562e018dcdefc1107ded
9426 F20110221_AAAEZX rogers_j_Page_01.QC.jpg
b802ad08603f3a9f9f70bd1364db2309
a203e85b7024ede9694599887765918ff6ddaa2b
32700 F20110221_AAAFBX rogers_j_Page_30.QC.jpg
c8c7e70f2d247c978c54914dac89ed50
5e493890a651fb1daf3c66dd25156c3fda65f482
F20110221_AAAESB rogers_j_Page_16.tif
0efb9f7b64d126e2e2ad52962e0924dc
2364cda641e11e5c0d4adaa4acc35850c8d97a1a
1051897 F20110221_AAAFGV rogers_j_Page_38.jp2
6f42e750a9431fb8980b15f60fce29ac
f2f4374acaae8a5a5c00a09d6db157524bba998e
5063 F20110221_AAAEZY rogers_j_Page_02.jpg
6b722a9f4f6ee1eae4f6bc0016cebcb4
69df953ce3031d767429db0e02f356c912726a3c
84171 F20110221_AAAFBY rogers_j_Page_31.jpg
57e123ca352424412cb8db6ebb3a3915
fb3caf705b91d398f10e1ead22aa9daffd6ebfe3
F20110221_AAAESC rogers_j_Page_17.tif
846ddee085cd91b521661115febf3798
f867d6940713d09476f71aa57aa8c33f9308987d
332104 F20110221_AAAFGW rogers_j_Page_39.jp2
9437a295d3b373f119ed6417646c08bc
cf947f1a949cff5063b33f0600e4e904ceefa681
1929 F20110221_AAAEXA rogers_j_Page_79.txt
3f40566bd1a16fb8f2d059ca9c777d1e
3dd5d63b6a6dcaab5f85777b0129ba9b80e592bb
1724 F20110221_AAAEZZ rogers_j_Page_02.QC.jpg
b3cda1649b17a41b1b2d9e26403a44f4
ca6d378da11b5350b93350940f936888713d5a2a
27800 F20110221_AAAFBZ rogers_j_Page_31.QC.jpg
e887229f58ed9a32a3fe6f08c6d5fcc1
944e969df8fc6d0ee02f7b3bf2e532968282960a
F20110221_AAAESD rogers_j_Page_18.tif
b988e8cba086972d0799f7c631572d56
905a76af06f166b62805f9cf276ce2405615a4d2
768994 F20110221_AAAFGX rogers_j_Page_40.jp2
06e20d2dae9c086a804e51e172cd5e5d
ac3124177cd1684699a90c696ec23206cd1c2216
1859 F20110221_AAAEXB rogers_j_Page_80.txt
25de1dc5a3618c812e51078ec9656d5a
c6b1b24d4df74e78fc333dd2020818fcf82a6959
F20110221_AAAESE rogers_j_Page_20.tif
f3b4cd7625e1b5e6a10092a1002ce370
ff8a882a1a0ec6aa3247fc3971330c6fcef0a0d0
1027209 F20110221_AAAFGY rogers_j_Page_41.jp2
4e77ce2fab846b4821190376d36f663c
736c408253aa07cac7d1fdc624d8da420c840d6a
97065 F20110221_AAAFEA rogers_j_Page_61.jpg
0f490b5afe107dd132643ac6dcfb8d89
e129c7b0ca945fec7442eaa4956c2d0f6adc7402
281 F20110221_AAAEXC rogers_j_Page_81.txt
b7516b4657690c991edd7c5d5ec16d23
adaa6ca7aabc379683d154f3d46a0b2da1605e3e
F20110221_AAAESF rogers_j_Page_21.tif
a6cbfc6ff28f89375991acd7b469470a
d607d30989898b09038ea466a4ffebb70dab2c3c
981716 F20110221_AAAFGZ rogers_j_Page_42.jp2
e3df7a0e9ca92f46e5c0006e885072ab
dd883a7b737402b822b7c7ebce24d74e728c80be
32958 F20110221_AAAFEB rogers_j_Page_61.QC.jpg
13ac414005adc569cbd3d5a3bed4c509
90f88a18932832227359f95c69971dad69e859a8
9882 F20110221_AAAEXD rogers_j_Page_01.pro
c2eb1a70aacd5b96bc1139b22a9528b1
843e4b9bd96cbdd471b202d3aa5f5d2f83e680e7
F20110221_AAAESG rogers_j_Page_22.tif
d005372a2fd1eed0de6b7ed052c2028a
9cde467ad72cc791067ba837c5c1f899c2980537
57423 F20110221_AAAFEC rogers_j_Page_62.jpg
b57910930dc83cb13afacc9f25b1978d
89065b53ad0390f69184b20daa7d46cfc0d0a544
1304 F20110221_AAAEXE rogers_j_Page_02.pro
0a354ae2ca894af940b00abfabf57e3b
1fecdb9566e5e292c89c594f3bbd649ad11e102d
F20110221_AAAESH rogers_j_Page_23.tif
7b9e7ee9555d57e36b021d377bc579f5
bdbabcf68f04e154657dbd9a1a1f8d0604e24e8e
7684 F20110221_AAAFJA rogers_j_Page_23thm.jpg
207745149abac281d155b47fabf829f2
fd43027b4f24d5b91d43abd7926fc82c41731a09
45376 F20110221_AAAEXF rogers_j_Page_03.pro
f864060c6ea6ecc42cf3c00e2c88b167
1fcf5f14ae79202f6915d8762b53e28dbea5e3e7
F20110221_AAAESI rogers_j_Page_24.tif
776a46e47e1aa1b322e2d05e0e0107ae
8b977f30361ab5ea8c1b1f0d69dfe6d99bd17ebd
19978 F20110221_AAAFED rogers_j_Page_62.QC.jpg
a5d4ffe44dc636cf5a1d812e4b18537e
eeace8b3f237f1784b6e1695d6ad74000629799c
6884 F20110221_AAAFJB rogers_j_Page_24thm.jpg
f812f5c3854399a0c29134c5bbb82a4d
620ec0149b7e2f80f76ef9f5f6917f7aad04712a
5490 F20110221_AAAEXG rogers_j_Page_04.pro
4de1d6652a039acb1a46c0f7c81e037c
77f6c3703ab7c7beefa42a3e6fb147cab5c6ced3
F20110221_AAAESJ rogers_j_Page_25.tif
cbbda523679c9f9b38c8c30065a3f269
1f0bc84d313a5fdae68fe177851536c956ffe9a4
67825 F20110221_AAAFEE rogers_j_Page_63.jpg
ceddfdc8adba237fc8611d9b544f23b3
2c79010579560b90daff5656589d64b987dabf6e
7010 F20110221_AAAFJC rogers_j_Page_25thm.jpg
87215260fe4fb14a0bd49875835f0d2c
920acf21b12058e51a166f66351dadfcd9a81dc6
67103 F20110221_AAAEXH rogers_j_Page_05.pro
450641c72b540a23a342127c43dac138
d45d5cb81c4f7600e603017d17ffa27ded5ab8f7
F20110221_AAAESK rogers_j_Page_26.tif
514fdaaf0b70c0f6894c5079c155320f
5b011f4e87ab635ac67f6b161bdabef429721740
6641 F20110221_AAAFJD rogers_j_Page_26thm.jpg
e7348951416f46ddc3ba63a41593104e
df9e16b46f3f7564e57eda047c59d763d8a5e162
67576 F20110221_AAAEXI rogers_j_Page_06.pro
13894004ee3397ed5d739b42e76e7c3b
945be7bce23563a00f2cf7afeaa44ba58699b441
F20110221_AAAESL rogers_j_Page_27.tif
c0f20c28d5490964a8a80d02efb5016a
bc1c8338651e0652cca8ec7f2873da6d795db55d
22204 F20110221_AAAFEF rogers_j_Page_63.QC.jpg
221255d9e85ade81230c2a4b538a4849
a9db341c1ef37791dd92241b3a5a899f8ff5aaaa



PAGE 1

1 BENZOTRIAZOLYL-2-PRO PYNONES AS NOVEL 1,3BISELECTROPHILES, BENZOTRIAZOLE-ASSISTED THI OACYLATION AND SYNTHESIS OF ENERGETIC MATERIALS By JAMES WILLIAM ROGERS 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 2006

PAGE 2

Copyright 2006 by James William Rogers

PAGE 3

iii ACKNOWLEDGMENTS I would like to foremost thank my wife Yu Hong, for her companionship and guidance through my graduate career. There are many days that I might have failed in my resolve to complete my goals if it were not for her love and ability to brighten my spirits when it seemed there was no hope. I w ould also like to thank friends and some of the co-workers I have met along my graduate career, who have helped me in my personal life as well as my graduate life in chemis try: Dr. Rachel Witeck, Dr. Gary Cunningham, Dr. Chia Pooput, Dr. Yian Zhai, and Hui Tao. I would also like to thank my parents, William and Barbara Rogers, who always believed in and encouraged me to strive to be a better man, as well as my sister, Jeannine Rogers, for her friendship. I would like to thank all my other family members who gave me support and love throughout my life. I am grateful for the help of Professo r Alan Katritzky, whose great mind for novel chemistry guided the research in these pages. I would also like to thank my mentors of the past, most notably Professor Timothy Patr ick, my research di rector at Southern Illinois University, where I recei ved a Master of Science in ch emistry. His belief in my abilities inspired me to continue my educat ion at the University of Florida. There are many teachers and instructors I would like to thank over the years, all of whom have encouraged me and supported me to continue my stated goals. I thank the Southern Illinois University at Edwardsville Chemistry Department for both my undergraduate and first two years of graduate study. The staff prepared me well for graduate school at the Ph D level. Lastly, I thank the graduate department of the

PAGE 4

iv University of Florida and the faculty of the Chemistry Department for accepting me, especially Professor James Deyrup, into th eir graduate program and for expanding my knowledge in chemistry greatly.

PAGE 5

v TABLE OF CONTENTS page ACKNOWLEDGMENTS.................................................................................................iii LIST OF TABLES............................................................................................................vii LIST OF FIGURES.........................................................................................................viii LIST OF SCHEMES..........................................................................................................ix ABSTRACT....................................................................................................................... xi CHAPTER 1 GENERAL INTRODUCTION................................................................................1 2 1 BENZOTRIAZOLYL-2-PRO PYNONES AS NOVEL 1,3BISELECTROPHILIC SYNTHONS....................................................................15 2.1 Introduction................................................................................................15 2.2 Results and Discussion..............................................................................17 2.3 Conclusion.................................................................................................21 2.4 Experimental..............................................................................................22 2.4.1 General Procedure for the Preparation of Substituted 1 Benzotriazolyl-2-propynones 2.14a,b............................................22 2.4.2 General Procedure for the Preparation of Pyrido[1,2a ]pyrimidin-2-ones 2.17ac...........................................................23 2.4.3 General Procedure for the Preparation of Quinolizin-2-ones 2.19af...........................................................................................24 2.4.4 General Procedure for the Prep aration of Pyrido[1,2-a]quinolin3-ones 2.21a,b and 5-Phenylthiazolo[3,2-a]pyrimidin-7-one (2.23)............................................................................................. 26 3 DEVELOPMENT OF BENZOTRIAZ OLE ASSISTED THIOACYLATION METHODOLOGIES.............................................................................................28 3.1 Introduction................................................................................................28 3.2 Results and Discussion..............................................................................30 3.3 Conclusion.................................................................................................34 3.4 Experimental Section.................................................................................34

PAGE 6

vi 3.4.1 General Pprocedure for the Preparation of 2-Amino-5nitrophenylamides 3.10a–h............................................................34 3.4.2 General Procedure for the Synthe sis of Aliphatic and Aromatic Thiocarbonyl-1 H -6-nitrobenzotriazoles 3.11a–g...........................37 3.4.3 General Procedure for the Prepar ation of Thionoesters 3.12a–c...40 4 SYNTHESES AND CHARACTERIZATI ON OF ENERGETI C MATERIALS.42 4.1 Introduction................................................................................................42 4.1.1 Synthesis and Characterization of Blowing Agents.......................42 4.1.2 Syntheses of Hypergolic Agents....................................................44 4.1.3 Synthesis of Dinitro-Substituted Five Membered Heterocycles....47 4.2 Results and Discussion..............................................................................47 4.2.1 Results Syntheses and Characte rization of Blowing Agents.........47 4.2.2 Results Synthesis of Hypergolic Agents........................................52 4.2.3 Results Nitration of Five Membered Heterocycles........................54 4.3 Conclusion.................................................................................................55 4.4 Experimental..............................................................................................55 4.4.1 General Procedure for the Preparation of Benzo[1,2,3,4]thiatriazine-1,1-dioxides 4.5-4.6............................56 4.4.2 General Procedure for the Prepar ation of Pyrazolium Nitrate 4.8....57 4.4.2.1 General Procedure for the Pr eparation of Hypergolic Aminals 4.9 and 4.10.........................................................57 4.4.2.2 General Procedure for the Pr eparation of Hypergolic Agent Dimethyl(2-pyrrolid in-1-yl-ethyl)amine 4.11.........58 4.4.2.3 General Procedure for the Pr eparation of Hypergolic Agent 1,3-(Dipyrrolidyl)propane 4.12...............................58 4.4.3 General Procedure for the Preparation of 2-Ethyl-3,5Dinitrothiophene 4.29....................................................................59 4.4.4 General Procedure for the Prep aration of 2,4-Dinitrothiophene 4.32, 2,5Dinitrothiophene 3.33....................................................59 5 CONCLUSION......................................................................................................60 LIST OF REFERENCES...................................................................................................62 BIOGRAPHICAL SKETCH.............................................................................................68

PAGE 7

vii LIST OF TABLES Table page 3-1 Preparation of thiocarbonylbenzotriazoles 3.6a–d. ..................................................31 3-2 Aliphatic and aromatic thiocarbonyl-1 H -6-nitrobenzotriazoles 3.11a–g. ................32 3-3 Thionoesters 3.12a-c ................................................................................................34

PAGE 8

viii LIST OF FIGURES Figure page 1-1 Electronic propertie s of benzotriazole........................................................................2 1-2 Methodologies for removal of benzotriazole.............................................................3 1-3 Graebe-Ulmann reaction............................................................................................4 1-4 Insertion of benzotriazole...........................................................................................4 1-5 Transformations with benzotriazole...........................................................................5 1-6 Cyclization mechanism for 1-benzotriazolyl-2-propynone........................................9 1-7 Blowing agents.........................................................................................................13 1-8 Hypergolic fuels.......................................................................................................13 2-1 Pyrido[1,2a ]pyrimidines possessing diverse biological activities..........................15 2-2 Mechanism of cyclization reaction..........................................................................21 3-1 X-ray structure of bis(benzotriazo lyl)-di-(4-methylphenylylthio)methane.............30 4-1 Blowing agents with reported melting points and DSCs.........................................43 4-2 Energetic Additives without reported TGA analysis...............................................44 4-3 Hypergolic fuels.......................................................................................................46 4-4 TGA analysis of compounds 4.5-4.7. ........................................................................50 4-5 X-ray of molecular complex of 4-nitropyrazole and oxalic acid 4.17 .....................51 4-6 TGA and DSC analysis of pyrazolium nitrate 4.8. ...................................................51

PAGE 9

ix LIST OF SCHEMES Scheme page 1-1 N -Acylbenzotriazoles from acid chlorides.................................................................6 1-2 N -Acylbenzotriazoles from sulfonylbenzotriazoles...................................................7 1-3 N -Acylbenzotriazoles from carboxylic acids and thionyl chloride............................7 1-4 N-,Cand S-Acylation of N -acylbenzotriazole..........................................................8 1-5 Cyclization reactions of 1-benzotriazolyl-2-propynones.........................................10 1-6 Synthesis of bis-(ben zotriazolyl)methanethione 1.44 ..............................................10 1-7 Synthesis of unsymmetrical diand trisubst ituted thioureas 1.46. ...........................11 1-8 Synthesis of thioacyl nitrobenzotriazoles 1.50. ........................................................11 1-9 Synthesis of thionoesters 1.52 ..................................................................................12 1-10 Synthesis of dinitrothiophenes.................................................................................14 2-1 Literature methods for synthesis of pyrido[1,2a ]pyrimidin-2-ones........................16 2-2 2-Pyridylacetonitrile with 4-methyleneoxetan-2-one...............................................17 2-3 Synthesis of substituted 1benzotriazolyl-2-propynones.........................................18 2-4 Reaction of 1-benzotriazol-1-yl-3 -phenylpropynone and 2-aminopyridines...........18 2-5 Reaction of 2-picolines and 1-benzotriazolyl-2-propynones...................................19 2-6 Reaction of 2-methylquinoline and 1-benzotriazolyl-2-propynones.......................20 2-7 Reaction of 2-aminothiazole and N -(phenylpropioyl)benzotriazole........................20 2-8 Syntheis of pyrimido[2,1b ]benzothiazoles.............................................................20 2-9 Attempted synthesis of 2.23, 2.17a and 2.19a from 3-phenylpropiolic acid..........21 3-1 Classical methods for the synthesis of thionoesters.................................................28

PAGE 10

x 3-2 Preparation of unsymmetrical diand tri-substituted thioureas 3.3 .........................29 3-3 Preparation of thiocarbonylbenzotriazoles 3.6a-d. ..................................................31 3-4 Preparation of thiocarbonyl-1 H -6-nitrobenzotriazoles............................................32 3-5 Preparation of thionoesters.......................................................................................33 4-1 Synthesis of 4.10 and 4.9. ........................................................................................46 4-2 Synthesis of dimethyl-(2-pyrrolidin -1-yl-ethyl)amine 4.11. ....................................47 4-3 Synthesis of 2-phenylbenz o[1,2,3,4]thiatriazine-1,1-dioxide 4.5 ............................48 4-4 Synthesis of compound 4.6 ......................................................................................48 4-5 Synthesis of bis-benzo[ 1,2,3,4]thiatriazi ne-1,1-dioxide 4.7 ....................................49 4-6 Synthesis of inter-chelating molecula r complex of 4-nitropyrazole and oxalic acid 4.17 ...................................................................................................................50 4-7 Synthesis of cyclic aminal 4.10 from formaldehyde................................................52 4-8 Synthesis of cyclic aminal 4.9 from formaldehyde..................................................52 4-9 Synthesis of cyclic aminal 4.10 via reduction with LAH.........................................53 4-10 Synthesis of cyclic aminal 4.9 via reduction with LAH...........................................53 4-11 Synthesis of N,N -dimethyl-2-(1-pyrrolidinyl)-1-ethanamine 4.11 ..........................53 4-12 Synthesis of 1,3-(dipyrrolidyl)propane 4.12. ...........................................................54 4-13 Synthesis of 2-ethy l-3,5-dinitrothiophene 4.29 ........................................................54 4-14 Synthesis of mixture of 2,44.32 and 2,5-dinitrothiophenes 4.33. ..........................55

PAGE 11

xi 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 1 BENZOTRIAZOLYL-2-PRO PYNONES AS NOVEL 1,3BISELECTROPHILES, BENZOTRIAZOLE-ASSISTED THI OACYLATION AND SYNTHESIS OF ENERGETIC MATERIALS By James William Rogers May 2006 Chair: Alan R. Katritzky Major Department: Chemistry New synthetic strategies for the synthesis of several target molecules are the theme of this work. 1-Benzotriazolyl-2-propynones were shown to be novel 1,3-bis-electrophilic synthons. These synthons provided a new route in the synthesis of pyrido[1,2 a ]pyrimidin -2-ones, 2 H -quinolizin-2-ones, pyrido[1,2a ]quinolin-3-ones, and thiazolo[3,2a ]pyrimidin-7-ones. These new 1,3-bis-electrophili c synthons were compared with previous 1,3-bis-electrophilic methodologies from the lite rature and expanded on the role of these synthons by novel synthesis of new heterocyclic systems. Aliphatic and aromatic thiocarbonyl-1H-6 -nitrobenzotriazoles were synthesized (Chapter 3) as novel thioacyla ting reagents. To show th eir synthetic utility, these thiocarbonyl-1H-6-nitrobenzotr iazoles were reacted with an alchohol to form the corresponding thionoesters.

PAGE 12

xii Chapter 4 summarizes the work accomplished in collaboration with the US Army on the reasonable synthesis and characterizati on of broadly defined energetic materials.

PAGE 13

1 CHAPTER 1 GENERAL INTRODUCTION Syntheses of heterocyclic compounds po ssessing synthetic utility, biological activity and desirable physical properties ar e a constant area of interest for organic chemists, medicinal chemists and material scientists. Efficient methodologies for the synthesis of target molecules through the use of convenient starting materials, mild conditions and less laborious isolation and pur ification are highly sought after. This dissertation provides novel s ynthetic routes to fused he terocycles, thionoesters and energetic materials. Versatile synthetic methodol ogies employing benzotriazole as a leaving group are covered in the first two chapters of this dissertation. Over the previous two decades, benzotriazole (Bt) has been used in countless synthetic processes including multistep preparations of drugs, preparation of biologically active compounds and synthetic analogs of natural products.1 This is due to the multifaceted nature of benzotriazole and its unique electronic properties that enable it to act as an electr on-donating or electronwithdrawing moiety, depending on the functi onal group attached to the benzotriazole nitrogen. Indeed, many applications of benzotriazole depend upon its leaving ability 1.1 its ability to enhance -proton acidity 1.2 and its electron donor properties 1.3 (Figure 11). Generally, benzotriazole is consider ed to be comparable with cyano and phenylsulfonyl groups as a leaving group 1.1 or as an activator of -CH proton loss 1.2 .1 Benzotriazole also possesses el ectron donating characteristics 1.3 when there is an heteroatom on the carbon attached to nitrogen.

PAGE 14

2 N N N C R X H N N N C R X H N N N C R X H 1.1 good leaving group 1.2 activates CH to proton loss 1.3 electron donor properties N N N X+H C R 1.4 N+N N R X N+N N R H X-1.5 1.6 Figure 1-1. Electronic prope rties of benzotriazole. Benzotriazole is an inexpensive and stab le compound that is highly soluble in ethanol, benzene, toluene, chloroform, DMF and is slightly soluble in water.2 It is also very soluble in basic solutions because of the acidity of the nitrogen hydrogen (pKa of 8.2).3 Benzotriazole is considered to be a usef ul synthetic auxiliary because it displays three important properties: i) it is readily removed at the end of a synthetic sequence (benzotriazole is especially advantageous b ecause it can be recovered at the end of the reaction and reused), ii) it is easily introdu ced at the beginning of a reaction, and iii) lastly it is stable to various reaction c onditions and can possibly activate other groups on the molecule. Benzotriazole has been proven in hundred s of publications to be a good leaving group and can be efficiently removed at the e nd of a synthetic sequen ce by i) nucleophilic substitution 1.11 4a-e ii) elimination 1.12 5a-e iii) hydrolysis 1.10 6a-e and iv) ring scission7 (Figure 1-2).

PAGE 15

3 N N N X R Y H N N N X+ R Y H Nu--H+4. Removal by Ring Scission H2O O R HY 3. Removal by Hydrolysis 1. Removal by Nucleophilic Substitution 2. Removal by elimination Nu R X Y H Y R X 1.7 1.8 1.9 1.10 1.11 1.12 Figure 1-2. Methodologies for removal of benzotriazole. The first three modes of re moval all involve initial di ssociation of benzotriazole into its anion 1.8 and formation of cation 1.9 Dissociation is a ssisted by a suitable hetero-atom X and by a proton or Lewis acid ca talyst which facilita tes the departure of benzotriazole. The leaving ability of benzot riazole is also heavily influenced by the presence of other functional groups exemp lified by group Y; for instance to remove benzotriazole by elimination, group Y must be connected to a hydr ogen (Figure 1-2). Removal of benzotriazole by ring scission is di fferent from the first three examples in that benzotriazole does not remain intact; in stead its ring structure is cleaved. Probably the most well known example of ring scissi on on benzotriazole is the Graebe-Ulmann reaction in which carbazole 1.16 is formed from loss of N2 from 1-phenylbenzotriazole 1.137 (Figure 1-3). The reaction is thought to form a diradical intermediate 1.14a or an iminocarbene intermediate 1.14b which then undergoes cyc lization to form (R)-4b H carbazole 1.15 which isomerizes via hydr ogen shift to carbazole 1.16

PAGE 16

4 N N N Ph -N2 N N N H H N 1.131.14a 1.14b 1.15 1.16 Figure 1-3. Graebe-Ulmann reaction. A good synthetic auxiliary should be able to be inserted into the molecule of interest quite readily, and indeed benzotriazole has been successfully inserted in many diverse systems. Benzotriazole derivatives can be obtained through displacement of a halogen in i) alkyl,8 or ii) acyl halides9, iii) though displacem ent of hydroxyl groups in alcohols,10 and by displacement of alkoxy groups in iv) acetals11 or ketals.12 Benzotriazole can also be insert ed by addition to v) aldehydes13 (including conjugate analogues), vi) imines,14 vii) iminium salts,15 and enamines16 (Figure 1-4). 1. RX +BtR-Bt 2 RCOX + BtRCOBt 3. ROH + BtR-Bt OR OR R R + BtBt OR R R By Substitution By Addition CO BtH OH Bt CN BtH HN Bt CN BtN Bt Bt= N N N 4. 5. 6. 7. Figure 1-4. Inserti on of benzotriazole. As stated earlier in the introduction a useful synthetic auxiliary should be stable to various reaction conditions and possibly activat e other groups on the molecule. There are several transformations from the literature in which benzotriazole does not leave and is

PAGE 17

5 retained after the reaction. The most important of these transformations are i) deprotonation,17 ii) substitution,18iii) addition,19iv) isomerization between 1and 2substituted benzotriazoles,20v) isomerization of benzotri azole within the molecule,21 and vi) proton loss followed by rearrangement22 (Figure 1-5). C Bt X H Bt X -H+ E+C Bt X E 1. Proton loss followed by reaction with electrophile C Bt X Nu-C Bt Nu X=unactivated, C=C or hetero(aroamtic), heteroatom X=halogen or OR 2. Substitution either alpha to Bt-group or otherwise CC NR2(or OR) BtC X C C C NR2 Bt X 3. Addition of Bt-C-X to C=C-Y N N N R N N N R 4. Isomerization of Bt1 and Bt2C C C Bt CC C Bt 5. Isomerization of Bt group within molecule C C C H Bt C C C Bt BtC C C H 6. Proton loss followed by rearrangement Figure 1-5. Transformations with benzotriazole. Due to the unique electronic properties of benzotriazole th e Katritzky group has developed numerous synthetic methodologies employing it as a synthetic auxiliary in the synthesis of countless heterocy cles as well as other organic molecules. These reactions

PAGE 18

6 are typically shorter, offer hi gher conversion to product, and avoid the use of unstable or toxic chemical reagents such as acid chlorides.1 Over the last couple of years the Katritz ky group has focused much of its attention on N -acylbenzotriazoles. Studies on N -acylazoles as acylating agents are nothing new; they have been studied since the 1960’s by the Staab group.23 N -Acylazoles have been typically synthesized from th e corresponding acid chlorides 1.16 and N acylbenzotriazoles 1.18 can also be synthesized in this manner23 (Scheme 1-1). R1 O Cl + Bt H R1 O Bt 1.16 1.171.18 Scheme 1-1. N -Acylbenzotriazoles from acid chlorides. Although the synthesis of N -acylazoles is routine, the requirement of their synthesis from acid chlorides is problematic and they can be both physiologically dangerous as well as unstable. Recently the Katritz ky group discovered two new methodologies for the synthesis of N -acylbenzotriazoles that do not require the use of acid chlorides. The first methodology uses a sulfonylbenzotri azole as a counter attack reagent.24, 25a When a carboxylic acid 1.19 is exposed to a suitable base such as Et3N the hydroxy group is deprotonated froming a carboxylate that can then undergo nucleophilic substitution with the electrophilic sulfonylbenzo triazole forming a mixed carboxylic sulf onic anhydride 1.20 Benzotriazole anion 1.21 is then thought to counterattack the mixed carboxylic sulfonic anhydride intermediate 1.20 to form the corresponding N -acylbenzotriazole 1.18 (Scheme 1-2).

PAGE 19

7 R1 OH O BtSO2R2Et3N R1 O O S O O R2 +Bt-+ R1 Bt O 1.191.20 1.21 1.221.18 Et3NH+ Scheme 1-2. N -Acylbenzotriazoles from sulfonylbenzotriazoles. The Katritzky group later found that N -acylbenzotriazoles 1.18 could be synthesized by simply treating the carboxylic acid 1.19 in the presence of thionyl chloride and excess benzotriazole 1.1726 (Scheme 1-3). This methodology is often more advantageous than synthesizing N -acylbenzotriazoles from the previous route (Scheme 12) since thionyl chloride a nd benzotriazole are commercia lly available while sulfonylbenzotriazole has to be prep ared in a separate step. R1 OH O R1 Bt O SOCl2 2.5 BtH S O Bt Bt and/or S O Cl Bt 1.19 1.18 1.17 1.23 1.24 Scheme 1-3. N -Acylbenzotriazoles from carboxylic acids and thionyl chloride. A wide range of N -acylbenzotriazoles have been synthesized through these two different methodologies, including alkyl, ar yl, heterocyclic, unsaturated, and other functionally substituted derivatives.24,26 There are several acid chlorides with the same functionalities as the synthesized N -acylbenzotriazoles that are unstable, difficult to prepare or in some cases unknown.27 Reactions with N -acylbenzotriazoles have been extensively studied by the Katritzky group over the past 5 years. N -Acylbenzotriazoles have been found to undergo N-,Cand S-acylation with the following reag ents: i) amines (ammonia, primary and secondary) to form amides,25a ii) thiols to form thiol esters,28 iii) heterocycles under Friedel-Crafts reaction conditions to form C-acylated heterocycles,29 C-acylated with iv) (a) ketones,25e (b) cyanides30 and (c) sulfones31 to form -diketones, -ketonitriles and -

PAGE 20

8 ketosulfones respectfully, v) ethyl acetoacetate to form -ketoesters and vi) acetylketones to form complex -diketones32 (Scheme 1-4). Bt O R1 1. NH3, NH2R2, NHR2R3N O R1 R2 R3 R1=Alkyl, Aryl R2,R3=H, Alkyl, Aryl2 H SR2R2S O R1 3. R1=Aromatics, Heteroaromatics R2=Ph, Bn, Et, COCH3, CH2CO2H Het O R1 3. Heterocycle TiCl4 or ZnBrR1=Alkyl, Aryl Hetfuran, thiophene, pyroles, indoles R3 O R2 4. R3 O R2 O R1 5. R1,R2 =H, Me,aryl R3 =Me,aryl R2 R3 CN R2 R3 CN O R1 R1,R2 =H, Me,aryl R3 =Me,aryl n -BuLi or t -BuOKL D ANE t3NEt3S O O R2 R3 6 n B u LiS O O R2 R3 R1 O EtO O O NaHR1 OEt O O R1=Alkyl, Aryl, heteroaryl R1,R2 =H, Me,aryl R3 =Me,aryl R2 O O N a HR1 R2 O O R1, R2=Alkyl, Aryl, heteroaryl 1.18 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 7.8 Scheme 1-4. N-,Cand S-Acylation of N -acylbenzotriazole. N -Acylbenzotriazoles have been succe ssfully acylated using a variety of nucleophiles and the yields have been compar able to other methods which mainly used acid chlorides as the acylating reagent.27 N -Acylbenzotriazoles offer advantages over the corresponding acid chlori des in their stability towards hydr olysis, their chemo-selectivity and crystallinity. It should be noted that they are especi ally advantageous when acid chlorides are unknown, difficult to prepare, hand le and/or store. For these reasons the Katritzky group has expanded the research on N -acylbenzotriazoles and created

PAGE 21

9 numerous examples of derivatives that have been successfully acylated with several types of nucleophiles. In Chapter 2 1-benzotriazolyl-2-propynone s are shown to be very interesting N acylbenzotriazoles because they behave as 1,3-bis-electrophiles. 1-Benzotriazolyl-2propynones undergo cyclization with 1,3-bi s-nucleophiles to form various unsaturated cyclic ketones through the followi ng mechanism (Figure 1-6). HX X+ R O Bt C R X HX OBt H+X=CH, NH HX XH -H+ -H+ R X HXO Bt R X -XO Bt XX OBt XX O -BtFigure 1-6. Cyclization mechanis m for 1-benzotriazolyl-2-propynone. 1-Benzotriazolyl-2-propynones 1.33 (Chapter 2) were reacted with 2-aminopyridines 1.35 2-picolines 1.34 2-methylquinoline 1.37 and 2-aminothiazole 1.36 to form pyrido[1,2a ]pyrimidin-2-ones 1.39 2 H -quinolizin-2-ones 1.38 pyrido[1,2a ]quinolin-3-ones 1.41 and thiazolo[3,2a ]pyrimidin-7-ones 1.40 in moderate to excellent yields (Scheme 1-5). Successful applications of N -acylbenzotriazoles as novel acylating reagents have also prompted investigation into a second area of study (chapter 3): the use of bis(benzotriazolyl)methanethione as a mild thioacylating reagent.33 Bis-(benzotriazolyl)methanethione 1.44 is easily prepared from 1-trimethylsilylbenzotriazole 1.43 and thiophosgene 1.42 in quantitative yield34 (Scheme 1-6).

PAGE 22

10 NNH2 R Bt O NN RO N R1 N R1RO NCH3 N RO N S NH2 N S N Ph O (7178%) (40%) (53%) (3981%) 1.33 1.34 1.35 1.36 1.37 1.38 1.39 1.401.41 R1 R1 Scheme 1-5. Cyclization reactions of 1-benzotriazolyl-2-propynones. S Cl Cl + BtTMS S Bt Bt 1.42 1.43 1.44 Scheme 1-6. Synthesis of bis -(benzotriazolyl)methanethione 1.44 There was only one example from the literature before 2003 in which bis(benzotriazolyl)-methanethione was reacted wi th an amine (aniline) to form a thiourea (diphenyl-thiourea).34 The Katritzky group greatly expande d the work for the preparation of unsymmetrical diand trisub stituted thioureas using compound 1.44 as a thiophosgene equivalent. First bis-(ben zotriazolyl)methanethione 1.44 was reacted with one equivalent of a primary amine to form 1-(al kyl/arylthiocarbamoyl)-benzotriazoles 1.45 in near quantitative yields (Schem e 1-7). Then compound 1.45 was further reacted with either a primary or secondary amine to form unsymme trical diand trisubstituted thioureas 1.46

PAGE 23

11 S Bt Bt RNH2 S Bt N H R 1.44 R2NH R1 S HN R R2N R1 1.45 1.46 Scheme 1-7. Synthesis of unsymmetrical diand trisubstituted thioureas 1.46. It was found by Katritzky et al. that the thiocarbamoylbenzotriazoles 1.45 synthesized were stable at room temperature for several weeks. Thiocarbamoylbenzotriazoles 1.45 are masked isothiocyanates and are superior to them because they are more stable and their reactions with amines are faster, higher-yielding and less laborious in isolation and purification.33 Chapter 3 of this dissertation expands upon the previous work on thiocarbamoylbenzotriazoles 1.45 by preparing a broad range of reag ents for thioacylation, namely thioacyl nitrobenzotriazoles 1.50 .35 A previous route establ ished by the Rapoport group was used to synthesize aliphatic, aromatic and heterocyclic substituted derivatives.36a,b Treatment of 4-nitrobenzene-1,2-diamine 1.47 with the corresponding acid chlorides 1.48 gave regioselectively the intermediate amides 1.49 which were then converted to the corresponding thioamides by phosphoruspentasulfide and then cyclized by treatment with sodium n itrate in acetic acid to yi eld the corresponding thioacyl nitrobenzotriazoles 1.50 (Scheme 1-8). NH2 NH2 O2N 1.47 NH2 NH O2N R O ROCl 1) P2S52) HONO N N N R S 1.48 1.49 1.50 R=alkyl, aryl, heteroaryl Scheme 1-8. Synthesis of thioacyl nitrobenzotriazoles 1.50. It was found that all th ioacyl nitrobenzotriazoles 1.50 were stable at room temperature for several weeks and they readily reacted with 1-naphthalenol 1.51 to produce thionoesters 1.52 in good to almost quantitative yield (Scheme 1-9).

PAGE 24

12 N N N R S + OH S R O R=alkyl, aryl, heteroaryl 1.50 1.511.52 NEt3 Scheme 1-9. Synthesis of thionoesters 1.52 As part of a collaborative project with the US Army on development of energetic materials (Chapter 4), synthesis of three different types of energetic materials was accomplished (blowing agents, hypergolic agents and dinitrosubstituted five membered heterocycles). Blowing agents are very well known as e xplosive formulations but they are not only limited to this role; for instance, di nitropentamethylenetet ramine (DNPT) and p tolylsulfonylhydrazine (PTS) are employed in the production of microcellular rubber.37 Some blowing agents such as azodicarbonamide (ADCA) are used in th e plastics industry to provide polymer films.38-40 Blowing agents are also useful additives in propellant formulations.41-43 The US Army employs trinitrotoluene (T NT) and cyclotrimethylenetrinitramine (RDX) formulations as explosives. Blowing ag ents included in these formulations ideally should display separate isotherms from the ot her components of the explosive mixture. Addition of these blowing agen ts in explosive formulations provides a means to temper the cook off violence of the explosion. The following compounds were synthesized as potential blowing agent candi dates from methodologies which could be easily scaled-up (Figure 1-7). The evaluation of the thermal properties of these compounds is included in chapter 4.

PAGE 25

13 S O2N N N S O2N N N S O2N N N N N N SO2 NH+NH N+O -O O1.53 1.54 1.55 1.56 Figure 1-7. Blowing agents. Hypergolic agents are compounds that can be used as fuels and oxidizers which ignite on contact with one another and th erefore do not need a source of ignition.44 Hypergolic propellants have advantages over other propellants such as cryogenics in that they are easily stored and are rela tively inert until they are in contact with the other agent. Since hypergolic propellants do not need an ignition s ource, they are often the propellant of choice for spacecr aft and satellites as they ar e required to stop and start their engines thousands of times over the desi gn life of the vehicle, thereby eliminating one source of possible failure.45 Synthesis of the following hypergolic fuels was requested by the US Army that could poten tially be scaled-up to provide 50-100 g quantities (Figure 1-8). N N N N N N Me Me N N Me Me Me Me 1.57 1.58 1.59 1.60 Figure 1-8. Hypergolic fuels. Dinitro derivatives of five-membered hetero cycles may be of interest as energetic materials and/or possible blowing agent candida tes. They have also been shown to have diverse biological activity; fo r instance 2,4-dinitroimidazole derivatives have been shown

PAGE 26

14 to be very effective agents in increasing the sensitivity of hypoxic ce lls toward irradiation in cancer radiotherapy.46 Numerous dinitro heterocycles have also been shown to be useful intermediates; for instance Padwa a nd Watterson recently c onverted dinitro furan into various polysubstituted phenols through SnAr nucleophilic substitution reactions.47 Two dinitro heterocy clic derivatives 1.62 1.64, 1.65 (dinitrothiophenes isolated as a mixture of isomers) were successfully synthe sized in moderate to excellent yield with more examples planned for future work (Scheme 1-10). S HNO3, TFAA S O2N NO2 1.611.62 S NH4NO3TFA, TFAA NO2 S S NO2 O2N NO2 O2N + ratio 1.5:1 1.63 1.641.65 Scheme 1-10. Synthesis of dinitrothiophenes. In summary, an efficient synthesis of three types of energetic materials was developed. The previously unreported deco mposition profiles for three blowing agent candidates were analyzed by thermal analys is for evaluation as possible munitions additives. The fourth blowing agent candidate’s 1.56 decomposition profile was analyzed by TGA and DSC. Also, several novel fu sed heterocyclic derivatives were synthesized by reacting 1,3-bis nucleophiles with 1-benzotriaz olyl-2-propynones. Finally, thioacyl nitrobenzotriazoles were shown to be effective thio acylating reagents and are a viable alternative to previ ous problematic routes.

PAGE 27

15 CHAPTER 2 1 BENZOTRIAZOLYL-2-PROPYNONES AS NOVEL 1,3-BISELECTROPHILIC SYNTHONS 2.1 Introduction As a structural motif pyrido[1,2a ]pyrimidines have shown very diverse biological activities,48 for this reason these compounds have become interesting synthetic targets over the previous years. Their structural mo tif can be seen below in the tranquilizer pirenperone,49a the antiallergic agent ramastine,49b an antiulcerative agent,49c and an antiasthmatic agent49d (Figure 2-1). N N O CH3N O F N N O CH3N NN N N O O NS O N N O OC2H5O N N CH3O N N N N K Pirenperone Tranquilizer Ramastine Antiallergic Agent Antiulce r ative TBX Antiasthmatic Agent Figure 2-1. Pyrido[1,2a ]pyrimidines possessing dive rse biological activities. All the examples from Figure 1 are pyrido[1,2a ]pyrimidin-4-ones which are the most studied class due to thei r biological activity. Due to the interests these compounds have generated numerous synthetic rout es are available for their synthesis.50 In comparison, pyrido[1,2a ]pyrimidin-2-ones are a less st udied class although there are

PAGE 28

16 several literature methods that were found (Scheme 1-1) for thei r synthesis: i) cyclization of 2-aminopyridine 2.1 with ethyl cyanoacetate 2.2 at 80–100 oC and 14 kbar;51 ii) the cyclization of 2-aminopyridin e with the Vilsmeier-Haack 2.3 reagent prepared in situ from N -alkyl -Narylethoxycarbonylacetamide and phosphor us oxychloride, which always affords a mixture of the pyrido[1,2a ]pyrimidin-2-ones and pyrido[1,2a ]pyrimidin-4ones;52 iii) reaction of phenylpropiolic ester 2.4 with 2-aminopyridine, which forms a significant amount of un desired side products;53,48 (iv) reaction of dimethyl hex-2-en-4yne-1,6-dioate 2.554 or allene-1,3-dicarboxylic esters 2.655 with 2-aminopyridines; and v) acid catalyzed cyclization of N -acetoacetylated 2-amino pyridines/picolines/quinolines 2.7 under microwave assisted synthesis.56 NNH2 NNH2 O H3CON Cl Ph R1 O C2H5O CN NN H CH3OO (v) NN RO NNH2 CO2Me CO2Et Ph NNH2 NNH2 CO2Me MeO2C CO2Me CO2Me + (i) R = NH2+ (ii) R = N(R1)Ph + (iii) R = Ph + (iva) R = (i) (ii) (iii) (iva) (ivb) + 2.1 2.1 2.1 2.1 2.1 2.2 2.3 2.4 2.52 6(v) R = CH3(ivb) R = CH2CO2Me 2.7 Scheme 2-1. Literature methods for synthesis of pyrido[1,2a ]pyrimidin-2-ones. Surprisingly compared to pyrido [1,2a ]pyrimidin-2-ones quino lizin-2-ones are of a sparsely studied class of compounds; there is only one reported synthetic procedure. Only one quinolizin-2-one derivative was found from the literature, 4-methyl-2-oxo-2 H quinolizine-1-carbonitrile 2.10 which is formed by the reac tion of 2-pyridylacetonitrile

PAGE 29

17 2.8 with 4-methyleneoxetan-2-one 2.9 (Scheme 2-2).57 There were no reported examples from the literature that used picolines in th e place of 2-aminopyridines in the reaction with acetylenic carboxyl ic acid derivatives to form th e corresponding quinolizin-2-ones. N CN O O N MeO CN + 2.8 2.9 2.10 Scheme 2-2 2-Pyridylacetonitrile with 4-methyleneoxetan-2-one. There are numerous examples in the literature which employ N -acylbenzotriazoles as mild and neutral N -acylating agents. Some examples include the preparation of primary, secondary, and tertiary amides25a including formylation25b and trifluoroacylation.25c N -Acylbenzotriazoles are used for regioselective C -acylation of ketone enolates into -diketones25e and are also used for the O -acylation of aldehydes.25d The Katritzky group has an effici ent method for the synthesis of N -acylbenzotriazoles from acetylenic-carboxylic acids.26 1-Benzotriazolyl-2-propynone s are formed from the reaction of acetylenic-carboxylic acids and thionyl chloride and benzotriazole. These compounds are 1,3-bis-electrophiles and their r eaction with 2-aminopyridines leads to an improved syntheses of pyrido[1,2a ]pyrimidin-2-ones. 2.2 Results and Discussion Two examples of alkyl and aryl substituted 1 benzotriazolyl-2-propynones were synthesized, 1-benzotriazol -1-yl-3-phenylpropynone and 1-benzotriazol-1-yl-oct-2-yn-1one 2.14a,b which were prepared in 87% and 95% yield (Scheme 2-3). 1-Benzotriazol-1yl-3-phenylpropynone 2.14a was previously reported by our group26; 1-benzotriazol-1-yloct-2-yn-1-one 2.14b is a novel compound.

PAGE 30

18 R OH O 2.5 SOCl23 BtH R Bt O + +2.14a: R = Ph (87 %) 2.14b: R = C5H11 (95 %) 2.11 2.12 2.13 Scheme 2-3 Synthesis of substituted 1-benzotriazolyl-2-propynones. The first attempted synthesis of pyrido[1,2a ]pyrimidine-2-one 2.17a (conducted at 80–100 oC in acetonitrile for 2–4h in a sealed tu be), found that a significant amount of byproduct 2.16 was obtained along with the desired product 2.17a In order to isolate the byproduct 1-benzotriazol-1-yl3-phenylpropynone, compound 2.14a and 2-aminopyridine 2.15a were reacted at a lower temperature 80 oC with refluxing and in less time (2 hr), compound 2.17a was isolated in 27% yiel d along with the by-product 2.16 in 46% yield (Scheme 2-4). The by-product 2.16 is probably formed by the counter attack of benzotriazole anion with 1-benz otriazol-1-yl-3-phenylpropynone 2.14a It was found that byproduct 2.16 formation was significantly decrea sed by conducting the reaction under harsher conditions using a sealed tube at 120 oC for 12 hours allowing clean conversion to the pyridopyrimidine 2.17a (R = Ph) in 71 % yield afte r column purification (Scheme 2-4). Use of 4and 5-methyl substituted 2-am inopyridines also result ed in the formation of corresponding pyridopyrimidines 2.17b and 2.17c in yields of 73% and 71%. R NNH2 Ph Bt O MeCN Bt O Ph Bt R NN PhO 2.17a: R=H (71%) 2.17b: R=8-methyl (73%) 2.17c: R=7-methyl (71%) + + 2.14a 2.16 120 oC 2.15a: R=H 2.15b: R=5-methyl 2.15c: R=4-methyl Scheme 2-4. Reaction of 1-benzotriazol-1-yl-3phenylpropynone and 2-aminopyridines. Synthesis of 2 H -quinolizin-2-ones was performe d by reacting 2-pi coline with 1benzotriazol-1-yl-3-phenylpropynone 2.14a in a sealed tube at 120 oC in acetonitrile for 12 hours. This afforded the expected quinolizin-2-one 2.19a in 61% yield (Scheme 2-5).

PAGE 31

19 Similarly, reactions of 1-benz otriazol-1-yl-3-phenylpropynone 2.14a and 1-benzotriazol1-yl-oct-2-yn-1-one 2.14b with 2-picoline derivatives afforded the corresponding 2 Hquinolizin-2-ones 2.19b-f in moderate to good yields. R1 N R2 R Bt O MeCN R1 N R2RO + 120oC 2.18 2.14a,b 2.19 Scheme 2-5 Reaction of 2-picolines and 1-benzotriazolyl-2-propynones. 2.19 R R1 R2 Yield (%) a Ph H H 61 b Ph H CN 81 c Ph H Ph 50 d Ph H Me 51 e C5H11 H H 39 f Ph 9-methyl H 53 Surprisingly few reports were found in th e literature on react ions of propionates and 2-picoline or its derivatives leading to the formation of fused ring systems. The reaction of 2-methylpyridine-1-oxide with me thyl-3-phenyl-2-propanoate to give methyl2-(2-methyl-3-pyridyl)-3-oxo-3-phenyl) propanoate is the only known analogue.58 1 Benzotriazolyl-2-propynones 2.14a,b react easily as 1,3-biselectrophilic synthons to give fused ring products, since they are very good acylating reagents. The N -acylbenzotriazole met hodology, developed for the preparation of pyrido[1,2a ]pyrimidin-2-ones and 2 H -quinolizin-2-ones, has also b een extended to provide access to the fused ring systems of pyrido[1,2a ]quinolin-3-ones and thiazolo[3,2a ]pyrimidin-7ones. Reactions of 2-methylquinoline 2.20 with 1-benzotriazol-1-yl-3-phenylpropynone 2.14a or 1-benzotriazol-1yl-oct-2-yn-1-one 2.14b in a sealed tube at 120 oC in

PAGE 32

20 acetonitrile afforded the expected 1-phenyland 1-pentylpyrido[1,2a ]quinolin-3-ones 2.21a,b in 40% yields (Scheme 2-6). NCH3 O Bt R MeCN N O R 2.21a: R=Ph (40 %) 2.21b: R=C5H11 (40 %) 120oC+2.20 2.14 a,b Scheme 2-6 Reaction of 2-methylquinoline a nd 1-benzotriazolyl-2-propynones. Reaction of 2-aminothiazole 2.22 with 1-benzotriazol1-yl-3-phenylpropynone 2.14a in a sealed tube at 120 oC in acetonitrile afforded the expected 5-phenylthiazolo [3,2a ]pyrimidin-7-one 2.23 in 54% yield (Scheme 2-7). N S NH2 Ph O Bt MeCN N S N Ph O +120oC 2.22 2.14a 2.23 54 % yield Scheme 2-7 Reaction of 2-aminothiazole and N -(phenylpropioyl)b enzotriazole. Synthesis of analogous pyrimido[2,1b ]benzothiazoles 2.26 from acetylenic acids 2.25 and 2-aminobenzothiazoles 2.24 has been previously reported (Scheme 2-8).59 N S + CO2H R3 NH2 N S N O R3 1-butanal R1 R2 R1 R2 2.24 2.252.26 Scheme 2-8. Syntheis of pyrimido[2,1b ]benzothiazoles. Application of this procedure to the synthesis of pyrido[1,2a ]pyrimidin-2-one 2.17a 2 Hquinolizin-2-one 2.19a and thiazolo[3,2a ]pyrimidin-7-one 2.23 did not provide the desired products in the cases of pyrido[1,2a ]pyrimidin-2-one 2.17a and thiazolo[3,2a ]pyrimidin-7-ones 2.23 For 2 Hquinolizin-2-one 2.19a only trace amounts of product were isolated from a complex re action mixture after 2 days (Scheme 2-9).

PAGE 33

21 N S + CO2H Ph NH2 N S N O Ph 1-butanal N + CO2H Ph 1-butanal NH2 N N O Ph N + CO2H Ph 1-butanal CH3 N O Ph 2.19a 2.17a 2.23 2.22 2.18a 2.15a 2.27 2.27 2.27 Scheme 2-9. Attempted synthesis of 2.23, 2.17a and 2.19a from 3-phenylpropiolic acid. The following reaction mechanism is proposed for either pyrido[1,2a ]pyrimidin-2ones 2.17 or 2 Hquinolizin-2-one 2.19 although the other fused ring systems would be analogous. First conjugate addition of the pyr idine nitrogen to the 1-benzotriazolyl-2propynone forming in allenoic intermediate followed by cyclocondensation, gave the corresponding fused heterocy clic ring (Figure 2-2). N X + R N C XHn-1 C C OBt R N XHn-1 COBt R N XHn-1 R OBt N Xn-2 R O -BtHX= CH3, NH2 H+-H++ O Bt Figure 2-2. Mechanism of cyclization reaction. 2.3 Conclusion In comparison, our N -acylbenzotriazole methodology offers shorter reaction times, cleaner conversion to products, and higher yi elds then the literature procedures to

PAGE 34

22 synthesize pyrido[1,2a ]pyrimidin-2-ones. 1 Benzotriazolyl-2-propynones were also shown to be useful synthons for the s ynthesis of new heterocyclic systems. 2.4 Experimental Melting points were determined using a Br istoline hot-stage microscope and are uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a 300 MHz NMR spectrometer in chloroformd solution. Elemental and mass spectroscopy analyses were performed by Analytical Labor atories, Dept. of Chem., University of Florida. THF was distilled from sodium-b enzophenone ketyl prior to use. All the reactions were performed in flame dried glassware and column chromatography was performed on silica gel (200–425 mesh). 2.4.1 General Procedure for the Preparation of Substituted 1 Benzotriazolyl-2propynones 2.14a,b To a solution of benzotriazole (2.96 g, 24.8 mmol) and thionyl chloride (5.55 mL, 20.8 mmol) in methylene chloride (20 mL), th e appropriate acid (8.3 mmol) was added. The reaction mixture was stirred at room te mperature for 3h. Solvent was removed under vacuum and the resultant solid was re-dissolved in ethyl acetate. The organic layer was washed with water, 1N NaOH (200 mL x 2), and brine. Recrystallization from ethyl acetate afforded the desired 1 benzotriazolyl-2-propynone s in 80–95% yields. 1-Benzotriazol-1-yl-3-phenylpropynone (2.14a). White microcrystals (87%), mp 119–123 oC. 1H NMR 7.31 – 7.63 (m, 4H), 7.73 – 7.78 (m, 1H), 7.84 – 7.87 (m, 2H), 8.22 (d, J = 8.1 Hz), 1H), 8.37 (d, J = 8.1 Hz, 1H). 13C NMR 81.5, 94.8, 114.1, 118.2, 120.5, 127.2, 129.5, 130.6, 131.3, 132.4, 133.4, 145.9, 149.8. Anal. Calcd for C15H9N3O: C, 72.86; H, 3.67; N, 16.99. Found: C, 72.55; H, 3.56; N, 16.98.

PAGE 35

23 1-Benzotriazol-1-yl-oct-2-yn-1-one (2.14b). Yellow oil (95%). 1H NMR 0.93 0.98 (m, 3H), 1.36 1.54 (m, 4H), 1.73 1.78 (m, 2H), 2.61(t, J = 7.2 Hz, 2H), 7.53 (t, J = 7.8 Hz, 1H), 7.68 (t, J = 7.8 Hz, 1H), 8.15 (d, J = 7.8 Hz, 1H), 8.27 (d, J = 8.1 Hz, 1H). 13C NMR 13.9, 19.4, 22.1, 27.1,31.0, 100.4, 114.2, 120.3, 126.3, 126.5, 130.5, 130.9, 146.2, 150.2. 2.4.2 General Procedure for the Preparation of Pyrido[1,2a ]pyrimidin-2-ones 2.17a–c. 1-Benzotriazol-1-yl-3-ph enylpropynone (200 mg, 0.90 mmol) and substituted 2aminopyridine (0.90 mmol) were added to acetonitr ile (3 mL) in a sealed tube and heated to 120 oC with stirring for 12 hours. Solvent wa s removed under vacuum and the crude mixture was separated by silica column chro matography (30% ethyl acetate/hexanes to remove benzotriazole, then 5% methanol/chl oroform to elute produc t). Recrystallization from ethyl acetate afforded the desired pyrido[1,2a ]pyrimidin-2-ones in 71–88% yields. 4-Phenyl-2 H -pyrido[1,2a ]pyrimidin-2-one (2.17a). Yellow microcrystals (71%), mp 226–228 oC (Lit. mp 227–228 oC).6 1H NMR 6.51 (s, 1H), 6.69 – 6.74 (m, 1H), 7.32 – 7.39 (m, 1H), 7.45 – 7.47 (m, 2H), 7.52 – 7.55 (m, 1H), 7.58 – 7.61 (m, 3H), 7.72 (d, J = 7.2 Hz, 1H). 13C NMR 112.6, 117.1, 125.3, 128.8, 129.6, 129.7, 130.8, 135.7, 148.6, 152.5, 168.1. Anal. Calcd For C14H10N2O: C, 75.66; H, 4.54; N, 12.60. Found: C, 74.90; H, 4.39; N, 12.54. 8-Methyl-4-phenylpyrido[1,2a ]pyrimidin-2-one (2.17b). Orange microcrystals (73%), mp 210–211 oC. 1H NMR 2.15 (s, 3H), 6.45 (s, 1H), 7.27 – 7.32 (m, 1H), 7.38 – 7.45 (m, 4H), 7.56 – 7.60 (m, 3H).13C NMR 18.0, 117.1, 122.7, 124.9, 126.9, 128.9, 129.7, 130.8, 131.1, 138.9, 148.5, 151.6, 168.3. Anal. Calcd For C15H12N2O: C, 76.25; H, 5.12; N, 11.86. Found: C, 75.20; H, 5.01; N, 12.08.

PAGE 36

24 7-Methyl-4-phenylpyrido[1,2a ]pyrimidin-2-one (2.17c). Red microcrystals (71%), mp 160–162 oC. 1H NMR 2.36 (s, 3H), 6.43 (s, 1H), 6.53 (d, 1H, J = 7.4 Hz), 7.13 (s, 1H), 7.40 – 7.43 (m, 2H), 7.56 – 7.61 (m, 4H). 13C NMR 21.3, 115.5, 116.8, 123.1, 128.9, 129.0, 129.6, 130.8, 131.0, 147.9, 148.4, 152.6, 168.4. Anal. Calcd For C15H12N2O: C, 76.25; H, 5.12; N, 11.86. Found: C, 75.77; H, 5.36; N, 11.40. 2.4.3 General Procedure for the Prepar ation of Quinolizin-2-ones 2.19a–f. 1-Benzotriazol-1-yl-3-phe nylpropynone or 1-benzotriaz ol-1-yl-oct-2-yn-1-one (0.90 mmol) and the appropriate 2-picoline derivative (0.90 mmol) were added to acetonitrile (3 mL) in a seal ed tube and heated to 120 oC with stirring for 12 hours. Solvent was removed under vacuum and th e crude mixture was separated by silica column chromatography (30% ethyl acetate/he xanes to remove benzotriazole, then 5% methanol/chloroform to elute product). Recrys tallization from ethyl acetate afforded the substituted quinolizin-2-ones in 50–81 % yields. 4-Phenylquinolizin-2-one (2.19a). Amber microcrystals (61%), mp 189-191 oC. 1H NMR 6.49 – 6.54 (m, 1H), 6.74 (d, J = 2.7 Hz, 1H), 6.85 (d, J = 2.7 Hz, 1H), 7.11 – 7.16 (m, 1H), 7.26 – 7.34 (m, 1H), 7.37 – 7.54 (m, 3H), 7.59 – 7.61 (m, 2H), 7.71 (d, J = 7.5 Hz, 1H). 13C NMR 111.5, 112.4, 124.4, 124.8, 128.4, 128.7, 129.1, 129.4, 129.6, 130.3, 132.9, 145.0, 146.0, 175.4. HRMS (EI) Found [M]+ 221.0852; C15H11NO requires 221.0841. 2-Oxo-4-phenyl-2 H -quinolizin-1-carbonitrile (2.19b). Amber microcrystals (81%), mp 170-172 oC. 1H NMR 6.76 – 6.82 (m, 2H), 7.30 (s, 1H), 7.46 – 7.49 (m, 2H), 7.55 – 7.58 (m, 1H), 7.62 – 7.65 (m, 3H), 7.82 – 7.91 (m, 2H). 13C NMR 94.9, 113.8, 115.5, 122.5, 125.2, 129.0, 129.2, 129.9, 130.9, 131.3, 131.7, 133.5, 147.05, 148.4.

PAGE 37

25 Anal. Calcd For C16H10N2O: C, 78.03; H, 4.09; N, 11.38. Found: C, 71.82; H, 3.96; N, 11.97. 1,4-Diphenylquinolizin-2-one (2.19c). Amber microcrystals (50%), mp 223–225 oC. 1H NMR 6.43 (ddd, J = 7.2, 6.3, 1.2 Hz, 1H), 6.93 (s, 1H), 6.95 (ddd, J = 7.5, 6.3, 1.2 Hz, 1H), 7.22 (d, J = 9.3 Hz, 1H), 7.40 – 7.44 (m, 3H), 7.50 – 7.56 (m, 4H), 7.60 – 7.63 (m, 3H), 7.73 (d, J = 7.2 Hz, 1H). 13C NMR 111.4, 123.3, 123.8, 124.4, 127.6, 127.9, 128.8, 129.2, 129.5, 129.7, 130.1, 131.0, 133.5, 134.8, 142.6, 145.1, 173.7. Anal. Calcd For C21H15NO: C, 84.82; H, 5.08; N, 4.71. Found: C, 84.29; H, 5.01; N, 4.66. 1-Methyl-4-phenylquinolizin-2-one (2.19d). Dark purple oil (51%). 1H NMR 2.36 (s, 3H), 6.41 (t, J = 6.3 Hz, 1H), 6.80 (s, 1H), 7.07 – 7.12 (m, 1H), 7.39 – 7.42 (m, 2H), 7.44 (d, J = 4.8 Hz, 1H), 7.48 – 7.55 (m, 3H), 7.68 (d, J = 7.5 Hz, 1H). 13C NMR 10.3, 111.0, 118.1, 122.0, 122.4, 127.7, 129.1, 129.4, 129.9, 130.0, 133.5, 141.6, 144.3, 174.4. Anal. Calcd for C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C, 66.53; H, 4.85; N, 5.48. 4-Pentylquinolizin-2-one (2.19e). Dark purple oil (39%). 1H NMR 0.95 (m, 3H), 1.37 –1.46 (m, 4H), 1.73 (t, J = 7.5 Hz, 2H), 2.83 (t, J =7.9 Hz, 2H), 6.54 (d, J = 4.2 Hz, 1H), 6.63–6.68 (m, 1H), 6.75 (d, J = 2.7 Hz, 1H), 7.06 – 7.11 (m, 1H), 7.16 – 7.19 (m, 1H), 7.82 (d, J = 7.5 Hz, 1H). 13C NMR 13.9, 22.3, 26.2, 31.3, 32.4, 111.2, 112.6, 122.7, 125.3, 127.2, 128.0, 145.0, 145.2, 175.8. HRMS (EI) Found [M]+ 215.1300; C14H17NO requires 215.1310. 9-Methyl-4-phenylquinolizin-2-one (2.19f). Red microcrystals (53%), mp 206208 oC. 1H NMR 2.40 (s, 3H), 6.42 (t, J = 7.2 Hz, 3H), 6.79 (s, 2H), 7.00 (d, J = 6.6 Hz, 1H), 7.42 – 7.45 (m, 2H), 7.57 –7.62 (m, 4H). 13C NMR 19.6, 109.0, 111.4, 124.1,

PAGE 38

26 127.9, 128.0, 129.1, 129.5, 130.1, 131.0, 133.6, 145.3, 146.5, 175.8. Anal. Calcd for C16H13NO: C, 81.68; H, 5.80; N, 5.95. Found: C, 68.25; H, 5.57; N, 5.56. 2.4.4 General Procedure for the Preparat ion of Pyrido[1,2-a]quinolin-3-ones 2.21a,b and 5-Phenylthiazolo[3,2-a]pyrimidin-7-one (2.23). 1-Benzotriazol-1-yl-3-phe nylpropynone or 1-benzotriaz ol-1-yl-oct-2-yn-1-one (0.90 mmol) and the appropriate substituted 2-methylquinoline or 2-aminothiazole (0.90 mmol) were added to acetoni trile (3 mL) in a sealed tube and heated to 120 oC with stirring for 12 hours. Solvent was remove d under vacuum and the crude mixture was separated by silica column chromatography (30% ethyl acetate/ hexanes to remove benzotriazole, then 5% methanol/chloroform to elute product). R ecrystallization from ethyl acetate afforded the pyrido[1,2a ]quinolin-3-ones in 40 % yield and 5phenylthiazolo[3,2a ]pyrimidin-7-one in 54% yield. 1-Phenylpyrido[1,2a ]quinolin-3-one (2.21a). Dark purple oil (40%). 1H NMR 6.57 (d, J = 3 Hz, 1H), 6.79 (d, J = 3 Hz, 1H), 6.95 – 7.08 (m, 3H) 7.22 – 7.27 (m, 1H), 7.31 – 7.36 (m, 3H), 7.38 – 7.45 (m, 3H), 7.52 – 7.55 (m, 1H). 13C NMR 114.3, 123.1, 124.0, 125.4, 125.6, 125.8, 127.4, 127.6, 128.2, 129.3, 129.4, 130.0, 135.3, 137.3, 145.7, 148.6, 177.7. Anal. Calcd For C19H13NO: C, 84.11; H, 4.83; N, 5.16. Found: C, 84.82; H, 4.72; N, 5.11. 1-Pentylpyrido[1,2a ]quinolin-3-one (2.21b). Dark purple oil (40%). 1H NMR 0.81 (t, J = 6.9 Hz, 3H), 1.17 – 1.22 (m, 4H), 1.61 (t, J = 7.2 Hz, 2H), 3.05 (t, J = 7.8 Hz, 2H), 6.47 (d, J = 2.4 Hz, 1H), 6.77 (d, J = 2.4 Hz, 1H), 6.95 (d, J = 9.0 Hz, 1H), 7.24 – 7.28 (m, 2H), 7.49 – 7.59 (m, 2H). 13C NMR 13.8, 22.2, 29.9, 31.1, 34.9, 113.5, 121.4, 123.5, 124.4, 125.9, 126.0, 127.9, 128.3, 219.2, 134.8, 145.3, 151.2, 177.7. Anal. Calcd For C18H19NO: C, 81.47; H, 7.22; N, 5.28. Found: C, 80.47; H, 7.33; N, 5.25.

PAGE 39

27 5-Phenylthiazolo[3,2a ]pyrimidin-7-one (2.23). White plates (54%), mp 161-164 oC (Lit. mp 191–194 oC).15 1H NMR 6.15 (s, 1H), 7.22 (d, J = 4.2 Hz, 1H), 7.35 (d, J = 4.8 Hz, 1H), 7.59 – 7.65 (m, 5H). 13C NMR 98.2, 109.8, 110.8, 123.3, 128.6, 129.2, 130.7, 131.2, 147.9, 166.5. Anal. Calcd For C12H8N2OS: C, 63.14; H, 3.53; N, 12.27. Found : C, 60.14; H, 3.48; N, 12.07. *Note while the mp was considerably lower then what the literature reported the author feel s that since the product was isolated as an amorphous solid the mp would be lower than uniform crystals.

PAGE 40

28 CHAPTER 3 DEVELOPMENT OF BENZOTRIAZO LE ASSISTED THIOACYLATION METHODOLOGIES 3.1 Introduction Thionoesters (R-C(S)-OR) have been a focu s of interest due to their different reactivities relative to their oxygen analogues.60,61 For example they can be desulfanated using Raney nickel to form ethers. 62 This is a good path to c onvert esters to ethers while avoiding problems associated with steric and functional limitations.63 Thionoesters have been shown to react with DAST under mild conditions to form -difluoroethers, which are compounds of current interest.64 1,3,4-Oxadiazoles65 can also be synthesized using thionoesters as starting materi al, these compounds have genera ted considerable interests due to their use as plant cell growth hormones, herbicides, and fungicides.66,67 Thionoesters have recently been found to be effective chain transfer agents in various polymerizations including styrene, met hyl acrylate and other related olefins.68 Several examples of various methodologies for the synthesis of thionoesters are depicted on Scheme 3-1 below. S R1 O R2 H2S, Pyridine (i) R2O OR2 R NH R1 O R2 BF4 -(ii) Na2S, CH3CN (iii) S R1 X HOR2 (iv) HOR2 C S R1 R (v) Xylene Reflux O R1 O R2 P4S10 Scheme 3-1. Classical methods fo r the synthesis of thionoesters.

PAGE 41

29 Example (i) is sulfur-hydroly sis of iminoesters with hydr ogen sulfide in pyridine. Unfortunately thioamides are often a major side product and the methodology was limited in scope69,70. Example (ii)is sulfo-hydrolysis of dialkoxycarbonium ions, which often results in mixtures requi ring lengthy purification techniques.71,72 Examples (iii) and (iv) are alcoholysis of thioacyl halides73 and thioketenes74 to thionoesters. Thioacyl halides are generally very unstable, only thio benzoyl chlorides see mu ch use. Aliphatic thioacyl halides decompose even at -70 oC.75 Thioketenes have a similar problem to thioacyl halides in that they are also very unstable and dimerize rapidly unless kept at a very low temperature. Direct thionation of an ester with phosphorus sulfide reagents to give the corresponding thionoester is shown in example (v) on Scheme 2.1.76 This is probably the best procedure fo r synthesizing thionoesters but the reaction conditions are long and harsh (refluxing xylene or toluene) and is limited to compounds which do not have sensitive functional groups. The Katritzky group has applied N -acylbenzotriazoles to the syntheses of amides,77 -keto sulfones,78 -substituted -ketonitriles,79 oxazolines and thiazolines,80 and C acylated-pyrroles and -indoles.81 The Katritzky group recently reported the application of thioacylating reagent, bis(be nzotriazolyl)methanethione 3 1 in the preparation of unsymmetrical diand tri-substituted thioureas 3.3 by intermediate 1(alkyl/arylthiocarbamoyl) benzotriazoles 3.233 (Scheme 3-2). N N N S Bt Bt NH2R S N H Bt R NH R1R2 S N H N R R1R2 Bt =3.1 3.2 3.3 Scheme 3-2. Preparation of unsymmetri cal diand tri-substituted thioureas 3.3

PAGE 42

30 This work has been greatly extended by preparing a range of reagents for thioacylation (RCSBt), thiocarbamoylat ion (RR'NCSBt), aryl/alkoxythioacylation (ROCSBt), and aryl/alkylthiothioacylation (RSC SBt). This report will detail the work completed on reagents for thioacylation, namely thioacyl nitrobenzotri azoles. Reactions of thioacyl nitrobenzotria zoles with oxygen nucleophile s gave the corresponding thionoesters in good yield. 3.2 Results and Discussion It should be noted that Rachel M. Witek of the Katritzky group found that the direct reaction of bis(benzotriazolyl)methanethione 3.1 with Grignard reagents provides low yields (12–34%) of bis(benzot riazolyl)diarylsulfidemethane s (Figure 3-1) instead of thiocarbonylbenzotriazoles. Due to these uns atisfactory results alternate routes to thiocarbonylbenzotriazoles were investigated. N N N N N N S S C27H22N6S2Exact Mass: 494.13 Mol. Wt.: 494.64 C, 65.56; H, 4.48; N, 16.99; S, 12.97 Figure 3-1. X-ray structure of bis(benzotriazoly l)-di-(4-methylphenylylthio)methane. In previously reported syntheses of thioam ides in one-pot reactions from Grignard reagents, carbon disulfid e, and amines mediated by 1-trifluoromethylsulfonylbenzotriazole;82a,b the putative intermediate thiocarbonyl benzotriazoles 3.6 were evidently formed, but were not isolated. Decomposition of analogous methyl-substituted thioacylimidazoles has been reported.83 1-Chlorobenzotriazole is used (instead of 1-

PAGE 43

31 trifluoromethylsulfonyl-benzotri azole) as the mediating reagen t which allows isolation of 3.6 in some cases (Scheme 3-3). Rachel M. Witek prepared thiocarbonylbenzotriazoles 3.6a-d from carbon disulfide, 1-chlorobenzotriazole and the re spective Grignard or organolithium reagents (Table 3.1). The benzenoid thiocarbonylbenzotriazoles (63–8 9%) are all stable reddish solids. Benzotriazol-1-yl-4-methylphenyl methanethione 3.6a displays the characteristic 1H NMR shifts for benzotriazole overlapping wi th aromatic shifts of the p-tolyl group 7.39 (d, J = 8.4 Hz, 2H), 7.55 (t, J = 7.5 Hz, 1H), 7.71 (t, J = 7.5 Hz, 1H), 8.14–8.19 (m, 3H), 8.39 (d, J = 8.4 Hz, 1H)}. A 13C NMR shift ~170 ppm is common for the thiocarbonyl in compounds 3.6a–d RMgBr CS2THF R S SMgBr 2 BtCl R S Bt R S N R1R2 R1R2NH3.4 3.5 3.6 3.7 Scheme 3-3. Preparation of thiocarbonylbenzotriazoles 3.6a-d. Table 3-1. Preparation of thiocarbonylbenzotriazoles 3.6a–d. 3.6 R % Yield a 4-Tolyl 63 b 4-Methoxyphenyl 89 c Phenyl 76 d 4-Chlorophenyl 42 One limitation of this method is that it is restricted to Grignard compatible functionalities. In addition, while benzenoid aryl Grignard reagents react quite smoothly to give thiocarbonylbenzotriazoles 3.6 only poor yields are atta ined for alkyl, alkynyl, and heteroaryl Grignard reagents. In Rachel’s hands, attempts to obtain n -butyl substituted thiocarbonylbenzotr iazole in higher yield by c onducting the reactions at 0 oC and at -78 oC failed. Likewise conversion of n -butyllithium to n -butylzinc bromide or n-

PAGE 44

32 butylcuprous bromide for reactions with carbon disulfide and 1-chloro benzotriazole also failed. The stability of non-benzenoid thiocarbonyl benzotriazoles thus appears to be poor. Rapoport utilized the route of Scheme 3-4 to obtain aliphatic thiocarbonyl-1 H -6nitrobenzotriazoles in good yields (48-67%). 36a,b Apparently, the electron-withdrawing nitro group on the benzotriazole moiety improves the stability and allo ws the isolation of aliphatic thiocarbonylbenzotriazoles 3.11 Following this methodology, several novel aliphatic and arom atic thiocarbonyl-1 H -6-nitrobenzotriazoles 3.11b–g were prepared (compound 3.11a was previously synthesized by Rapoport) ( Scheme 3-4, Table 3-2). N S R N N O2N NH2NH2O2N HONO NH O R NH2O2N 3.8 3.9 3.10 3.111) 2) RCOCl P2S5 Scheme 3-4. Preparation of thiocarbonyl-1 H -6-nitrobenzotriazoles. Table 3-2. Aliphatic and aromatic thiocarbonyl-1 H -6-nitrobenzotriazoles 3.11a–g. 3.11 Acid Chloride 3.9 R = Amide 3.10 (% yield) Thiocarbonyl-6-nitrobenzotriazole 3.11 (% yield from 3.10) a Ethyl 84 52 b 4-Methylphenyl 98 80 c 2-Furanyl 95 80 d 4-Nitrophenyl 83 69 e 4-Methoxyphenyl 86 66 f 4-Bromophenyl 99 45 g Pentyl 81 53 h 2-Thienyl 91 81 Treatment of 4-nitrobenzene-1,2-diamine 3.8 with the respective acid chlorides 3.9 gave regioselectively the intermediate amides 3.10 (83–99%). Resonance and the inductive effect of the nitro group lowers the nucleophilicity of th e amino group in the para position, leaving the meta amino group to attack the carbonyl of the acid chloride

PAGE 45

33 3.9 Amides 3.10 were converted to thioamides in crude yields of 59–96% by stirring at room temperature with phosphorus pentasul fide (Scheme 2-3, Table 2-2). Thioamides were cyclized by treatment with sodium nitr ite and acetic acid to afford thiocarbonyl-1 H 6-nitrobenzotriazoles 3.11a–g in 45–80% yields from the corresponding amides 3.10 Thiocarbonyl-6-nitro-1 H -benzotriazoles 3.11a–g are all stable reddish solids. (6Nitrobenzotriazole-1-yl)propane-1-thione 3.11a shows the characteristic 1H NMR {8.31 (d, J = 8.9 Hz, 1H), 8.44 (dd, J = 8.9, 1.8 Hz, 1H), 9.74 (s, 1H)} and 13C NMR shifts 113.1, 121.2, 121.7, 131.7, 149.0, 149.4), which correspond to 6-nitro-1Hbenzotriazole. The thiocarbonyl 13C NMR shift of thiocarbonyl-6-nitro-1 H -benzotriazoles 3.11 is further downfield compared to thiocarbonylbenzotriazoles 3.6 and is found at 211.6 ppm for 3.11a Although this method is general a nd alkyl derivatives are obtained in moderate overall yields (44–72%), from 4-nitrobenzene-1,2-diamine 3.8 and the respective acid chlorides 3.9 the lengthy 3-step procedure is a drawback. Thus, the Grignard method of Scheme 2 is the pref erred means of obtaining arylthiocarbonylbenzotriazoles while Rapoport’s sy nthesis is preferred for alky l, alkynyl, and heteroaryl thiocarbonylbenzotriazoles. Thiocarbonyl-6-nitrobenzotriazoles 3.11 e,d,h were reacted with 1-naphthol providing thionoesters 3.12a-c in 62–99% yields (Sch eme 3-5, Table 3-3). N N N S R NO2 + OH R S O 3.11 d,e,h 3.12 a-c Scheme 3-5. Preparation of thionoesters.

PAGE 46

34 Table 3-3 Thionoesters 3.12a-c Thionoesters 3.12 Alcohol Thioacylating Agent R = Yield (%) a 1-Naphthyl4-Methoxyphenyl (3.10e)88 b 1-Naphthyl4-Nitrophenyl (3.10d) 99 c 1-Naphthyl2-Thienyl (3.10h) 62 3.3 Conclusion Application of benzotriazole reagents fo r aryl/alkoxythioacylati on (ROCSBt) to the syntheses of several novel thionoesters has been successfully developed. Advantages of benzotriazole methods are primarily that use of unstable or hazardous reagents is avoided, the mild conditions employed are to lerable of a large va riety of functional groups, and yields are comparable and in ma ny cases higher than previously reported methods. 3.4 Experimental Section Melting points were determined using a Br istoline hot-stage microscope and are uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a 300 MHz NMR spectrometer in chloroformd solution. Elemental and mass spectroscopy analyses were performed by Analytical Labor atories, Dept. of Chem., University of Florida. THF was distilled from sodium-b enzophenone ketyl prior to use. All the reactions were performed under a nitrogen at mosphere and in flame dried glasswares. Column chromatography was perf ormed on silica gel (200–425 mesh). 3.4.1 General Pprocedure for the Preparat ion of 2-Amino-5-nitrophenylamides 3.10a–h. Et3N (3.0 g, 30 mmol) was added to a solu tion of 4-nitrobenzene-1,2-diamine (3.06 g, 20 mmol) in THF (100 mL) at –40 oC, followed by dropwise addition of the respective acid chloride (20 mmol) The mixture was stirred at –40 oC for 3h and at rt overnight. The precipitate was filtered off and the filtrate evaporated to dryness in vacuo

PAGE 47

35 The residue was recrystallized from Et OH to afford the desired 2-amino-5nitrophenylamides 3 10a–h in 81–99 % yields. N -(2-Amino-5-nitrophenyl) propionamide (3.10a). Yellow microcrystals (84 %), mp 189–191 oC, (Lit.23 mp 191 oC). 1H NMR 1.10 (t, J = 7.6 Hz, 3H), 2.38 (q, J = 7.6 Hz, 2H), 6.49 (s, 2H), 6.76 (d, J = 9.0 Hz, 1H), 7.84 (dd, J = 9.0, 2.5 Hz, 1H), 8.27 (d, J = 2.5 Hz, 1H), 9.13 (s, 1H). 13C NMR 9.6, 28.9, 113.6, 121.2, 121.7, 122.6, 135.5, 148.9, 172.6. N -(2-Amino-5-nitrophenyl)-4-methylbenzamide (3.10b). Yellow needles (98%), mp 197–198oC. 1H NMR 2.39 (s, 3H). 6.59 (s, 2H), 6.82 (d J = 9.1 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H), 7.91 (d J = 9.2 Hz, 1H), 7.93 (d, J = 8.1 Hz, 2H), 8.15 (d, J = 2.6 Hz, 1H), 9.68 (s, 1H). 13C NMR 21.0, 113.9, 121.4, 123.5, 128.0, 128.8, 131.4, 135.4, 141.6, 150.6, 165.9. Anal. Calcd. For C14H13N3O3: C, 61.99; H, 4.83; N, 15.49. Found: C, 62.35; H, 4.76; N, 15.13. N -(2-Amino-5-nitrophenyl)furan-2-carboxamide (3.10c). Yellow needles (95 %), mp 176–178oC. 1H NMR 6.61 (s, 2H), 6.71 (dd, J = 3.3, 1.5 Hz, 1H), 6.81 (d, J = 9.0 Hz, 1H), 7.33 (d, J = 3.6 Hz, 1H), 7.91–7.94 (m, 2H), 8.06 (d, J = 2.4 Hz, 1H), 9.69 (s, 1H). 13C NMR 112.1, 113.9, 114.9, 120.4, 123.8, 135.4, 145.6, 147.4, 150.9, 157.0, 168.0. Anal. Calcd. For C11H9N3O4: C, 53.44; H, 3.67; N, 17.00. Found: C, 54.65; H, 3.28; N, 13.25. N -(2-Amino-5-nitrophenyl)-4-nitrobenzylamide (3.10d). Brown needles (83%), mp 303–305 oC. 1H NMR 6.58 (s, 2H), 6.84 (d, J = 9 Hz, 1H), 7.93 (dd, J = 9, 2.4 Hz, 1H), 8.25–8.30 (m, 4H), 8.38 (s, 1H). 13C NMR 113.6, 122.8, 123.1, 123.8, 129.3,

PAGE 48

36 129.6, 129.7, 148.0, 148.4, 150.8, 193.5. Anal. Calcd. For C13H10N4O5: C, 51.66; H, 3.33. Found: C, 52.03; H, 3.39. N -(2-Amino-5-nitrophenyl)-4-methoxybenzylamide (3.10e). Brown needles (86%), mp 221–224 oC. 1H NMR 3.84 (s, 3H), 6.59 (s, 2H), 6.80 (d, J = 9.3 Hz, 1H), 7.08 (d, J = 9.3 Hz, 2H), 7.91 (dd, J = 9.3, 2.7 Hz, 1H), 8.00 (d, J = 2.7 Hz, 1H), 8.11 (d, J = 2.4 Hz, 1H), 9.62 (s, 1H). 13C NMR 55.6, 113.6, 114.0, 121.7, 123.7, 130.1, 130.8, 135.5, 150.9, 162.1, 165.6, 204.5. Anal. Calcd. For C14H13N3O3: C, 58.53; H, 4.56; N, 14.63. Found: C, 58.55; H, 4.57; N, 14.09. N -(2-Amino-5-nitrophenyl)-4-bromobenzylamide (3.10f). Brown needles (99%), mp 222–223 oC. 1H NMR 6.65 (s, 2H), 6.80 (d, J = 9 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.91–7.98 (m, 3H), 8.11 (s, 1H), 9.83 (s, 1H). 13C NMR 114.0, 121.1, 124.0, 125.6, 130.3, 131.4, 133.5, 135.4, 151.0, 161.8, 165.4. Anal. Calcd. For C13H10NBrO2: C, 46.45; H, 3.00; N, 12.50. Found: C, 46.34; H, 2.93; N, 11.89. N -(2-Amino-5-nitrophenyl)hexylamide (3.10g). Brown needles (81%), mp 130– 131 oC. 1H NMR 0.90 (t, J = 6.6 Hz, 3H), 1.32–1.34 (m, 4H), 1.62 (quintet, J = 6.6 Hz, 2H), 2.37 (t, J = 6.6 Hz, 2H), 6.49 (s, 2H), 6.78 (d, J = 9 Hz, 1H), 7.85 (dd, J = 9.0, 2.4 Hz, 1H), 8.31 (d, J = 2.4 Hz, 1H), 9.16 (s, 1H). 13C NMR 14.0, 22.1, 24.9, 31.1, 36.0, 113.8, 121.2, 121.9, 122.7, 135.7, 148.8, 172.1. Anal. Calcd. For C12H17N3O3: C, 57.36; H, 6.82; N, 16.72. Found: C, 57.88; H, 7.04; N, 15.97. N -(2-Amino-5-nitrophenyl)thiophe ne-2-carboxamide (3.10h). Brown needles (91%), mp 192–196 oC. 1H NMR 6.65 (s, 2H), 6.81 (d, J = 9 Hz, 1H), 7.22–7.25 (m, 1H), 7.86–7.95 (m, 2H), 8.03–8.09 (m, 2H), 9.81 (s, 1H). 13C NMR 114.0, 120.8,

PAGE 49

37 124.0, 128.2, 129.9, 131.9, 135.5, 139.5, 151.1, 160.8, 167.6. Anal. Calcd. For C11H9N3O3S: C, 50.18; H, 3.45; N, 15.96. Found: C, 49.98; H, 3.29; N, 15.43. 3.4.2 General Procedure for the Synthesis of Aliphatic and Aromatic Thiocarbonyl-1 H -6-nitrobenzotriazoles 3.11a–g. Phosphorus pentasulfide (2.22g, 10 mmol) was mixed with Na2CO3 (0.54 g, 5 mmol) in dry THF (150 mL). The mixture was st irred at rt for 1h and then cooled to 0 oC. The amide 9 (10 mmol) was added in one portion and the resulting mixture stirred at 0 oC for 3 hrs and rt for 10 hrs. The mixture was filtered and the filtrate evaporated to dryness, the residue was dissolved in EtOAc (100 mL) and washed with 5 % NaHCO3 (2 x 30 mL), and the aqueous layers back-extract ed with EtOAc (100 mL). The combined organic layers were washed with brine, dried with MgSO4 and evaporated to obtain a residue. The residue was placed on a silica-gel column and eluted with hexanes/ EtOAc (5:1) to give thioamides in crude yields of 59–96 %. Sodium nitrite (0.21 g, 3 mmol) was added to a stirred solutio n of the obtained thioamide (2 mmol) dissolved by gentle warming in aqueous acetic acid 95 % (25 mL) and then cooled to 0 oC. The resulting mixt ure was stirred at 0 oC for 45 min., then icecold water (100 mL) was added and the prec ipitated product was filtered and washed with water. Compound 3.11g was an exception requiring so nication and extraction with EtOAc, which entailed washing the aqueous solution three times with 50 mL EtOAc, collection of the organic layers and washing them with water (2 x 30mL) and brine (40 mL), drying with sodium sulfate, and filtration. The obtained solid was dried in vacuo overnight to afford the desired thiocarbonyl-1 H -6-nitrobenzotriazoles 3.11a–h in 45–81 % yields from the amides 3.10a-h

PAGE 50

38 (6-Nitrobenzotriazol-1-yl) propane-1-thione (3.11a). Orange microcrystals (52 %), mp 107–109 oC, (Lit.23 mp 108 oC). 1H NMR 1.54 (t, J = 7.1 Hz, 3H), 3.79 (q, J = 7.1 Hz, 2H), 8.31 (d, J = 9.0 Hz, 1H), 8.44 (dd, J = 9.0, 1.8 Hz, 1H), 9.74 (s, 1H). 13C NMR 13.4, 40.6, 113.1, 121.2, 121.7, 131.7, 149.0, 149.4, 211.6. (4-Methylphenyl)-(6-nitrobenzotriazol-1-yl)methanethione (3.11b). Red microcrystals (80 %), mp 140–141 oC. 1H NMR 2.45 (s, 3H), 7.29 (d, J = 8.0 Hz, 2H), 7.72 (d, J = 8.0 Hz, 2H), 8.32 (d, J = 9.0 Hz, 1H), 8.44 (dd, J = 9.0, 1.1 Hz, 1H), 9.42 (s, 1H). 13C NMR 21.8, 112.1, 121.2, 121.5, 129.1, 131.2, 133.1, 139.4, 145.1, 148.8, 148.9, 200.5. Anal. Calcd. For C14H10N4O2S: C, 56.37; H, 3.38; N, 18.78. Found: C, 56.65; H, 3.29; N, 18.69. Furan-2-yl-(6-nitrobenzotr iazol-1-yl)-methanethione (3.11c). Orange microcrystals (80%), mp 162 oC. 1H NMR 6.79 (dd, J = 3 Hz, 1.5 Hz, 1H), 7.66 (d, J = 3.6 Hz, 1H), 8.00 (d, J = 0.9 Hz, 1H), 8.32 (d, J = 9 Hz, 1H), 8.43 (dd, J = 9 Hz 2.1 Hz, 1 H), 9.47 (d, J = 1.8 Hz, 1H). 13C NMR 112.1, 114.4, 121.2, 121.4, 122.4, 132.9, 148.6, 148.8, 151.8, 154.3, 180.1. Anal. Calcd. For C11H6N4O3S: C, 48.17; H, 2.21. Found C, 47.83; H, 2.12. (4-Nitrophenyl)-(6-nitrobenzotriazol-1-yl)methanethione (3.11d). Orange needles (69%), mp 174 oC. 1H NMR 7.46 (d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.7 Hz, 2H), 7.93 (d, J = 8.7 Hz, 1H), 8.02 (d, J = 8.7 Hz, 2H), 9.00 (d, J = 1.8 Hz, 1H). 13C NMR 114.3, 114.7, 121.1, 123.4, 123.9, 130.9, 131.4, 136.4, 150.2, 166.0, 208.0. Anal. Calcd. For C13H7N5O4S: C, 47.42; H, 2.14 ; N, 21.27. Found C, 47.50; H, 2.02 ; N, 20.93. (4-Methoxyphenyl)-(6-nitrobenzotriazol-1-yl)methanethione (3.11e). Orange needles (66%), mp 162 oC. 1H NMR 3.93 (s, 3H), 6.98 (d, J = 9.0 Hz, 2H), 7.86 (d, J =

PAGE 51

39 9.0 Hz, 2H), 8.31 (d, J = 9.0 Hz, 1H), 8.42 (dd J = 9.0 Hz, 2.1 Hz, 1H), 9.37 (d, J = 2.1 Hz, 1H). 13C NMR 55.8, 112.0, 113.9, 112.1, 133.3, 134.0, 134.7, 148.6, 148.9, 164.8, 198.4. Anal. Calcd. For C14H10N4O3S: C, 53.50; H, 3.21; N, 17.82. Found C, 53.61; H, 3.14; N, 17.62. (4-Bromophenyl)-(6-nitro-benzo triazol-1-yl)methanethione (3.11f). Orange micro-crystals (45 %), mp 170 oC. 1H NMR 7.67–7.74 (m, 4H), 8.39 (d, J = 9 Hz, 1H), 8.52 (dd, J = 9, 1.8 Hz, 1H), 9.54 (d, J = 2.1 Hz, 1H). 13C NMR 112.1, 121.4, 121.9, 128.8, 131.6, 132.1, 132.8, 140.6, 149.0, 149.1, 199.6. Anal. Calcd. For C13H7BrN4O2S: C, 42.99; H, 1.94. Found: C, 42.81; H, 1.79. (6-Nitrobenzotriazol-1-yl)-1-hexylthioamide (3.11g). Yellow microcrystals (53%), mp 94–97 oC. 1H NMR 0.94 (t, J = 6.9 Hz, 3H), 1.37–1.52 (m, 4H), 1.95–2.05 (m, 2H), 3.78 (t, J = 7.5 Hz, 2H), 8.30 (d, J = 9.0 Hz, 1H), 8.44 (dd, J = 9.0, 1.8 Hz, 1H), 9.79 (d, J = 2.1 Hz, 1H). 13C NMR 13.9, 22.3, 29.4, 31.1, 47.6, 113.1, 121.2, 121.8, 131.7, 149.1, 149.4, 210.7. Anal. Calcd. For C12H14N4O2S: C, 51.78; H, 5.07; N, 20.13. Found: C, 52.14; H, 5.12; N, 19.79. (6-Nitrobenzotriazol-1-yl)thiophen-2-yl methanethione (3.11h). Orange microcrystals (81%), mp 134 oC. 1H NMR 7.25 (dd, J = 4.0, 1.2 Hz, 1H), 7.97 (d, J = 4.8 Hz, 1H), 8.10 (d, J = 4.0 Hz, 1H), 8.31 (d, J = 8.7 Hz, 1H), 8.42 (d, J = 8.7 Hz, 1H), 9.45 (s, 1H). 13C NMR 112.3, 121.2, 121.4, 129.2, 133.0, 136.5, 140.5, 146.6, 148.7, 187.3. Anal. Calcd. For C11H6N4O2S2: C, 45.51; H, 2.08, N, 19.30. Found: C, 44.66; H, 1.90; N, 18.45.

PAGE 52

40 3.4.3 General Procedure for the Preparation of Thionoesters 3.12a–c. The appropriate alcohol (0.5 mmol) and Et3N (0.05 g, 0.5 mmol) were added to the respective thiocarbonyl6-nitrobenzotriazole 3.11a-h dissolved in CH2Cl2 (30 mL) at rt. Stirring was continued overnight, then solv ent was removed by rotary evaporation. The residue was redissolved in EtOAc (100 mL), washed with 5% Na2CO3 solution (3 x 100 mL), 1M HCl (2 x 100 mL), water, and brine. The collected organi c layers were dried with Na2SO4, and the solvent was removed under vac uum. Recrystallization from EtOAc/ hexanes afforded thionoesters 3.12a–c O -Naphth-1-yl 4-metho xythiobenzoate (3.12a). Yellow needles (88%), mp 93–95 oC. 1H NMR 3.91 (s, 3H), 6.98 (d, J = 9.0 Hz, 2H), 7.24–7.27 (m, 1H), 7.44–7.56 (m, 3H), 7.80 (t, J = 6.3 Hz, 2H), 7.90 (d, J = 7.8 Hz, 1H), 8.49 (d, J = 9.0 Hz, 2H). 13C NMR 55.7, 113.7, 119.0, 121.6, 125.4, 126.4, 126.6, 126.8, 128.2, 131.0, 131.8, 134.8, 151.0, 164.3, 209.6. Anal. Calcd. For C18H14O2S: C, 73.44; H, 4.79. Found: C, 72.65; H, 4.89. O -Naphth-1-yl 4-nitrothiobenzoate (3.12b). Red needles (99%), mp 139–140 oC. 1H NMR 7.28 (d, J = 7.5 Hz, 1H), 7.46–7.59 (m, 3H), 7.73 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.94 (d, J = 7.8 Hz, 1H), 8.35 (d, J = 9.0 Hz, 2H), 8.61 (d, J = 9.0 Hz, 2H). 13C NMR 118.6, 121.0, 123.6, 125.4, 126.1, 126.75, 126.84, 127.0, 128.4, 130.2, 134.8, 141.7, 150.4, 150.5, 207.2. Anal. Calcd. For C17H11NO3S: C, 66.01; H, 3.58; N, 4.53. Found: C, 66.07; H, 3.47; N, 4.45. O -Naphth-1-yl 2-thienylcarbothioate (3.12c). Yellow needles (62%), mp 97–98 oC. 1H NMR 7.08 (dd, J = 4.8, 3.9 Hz, 1H), 7.24 (d, J = 7.5 Hz, 1H), 7.39–7.49 (m, 3H), 7.57 (dd, J = 4.8, 1.2 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.81–7.85 (m, 2H), 8.07 (dd, J = 3.9, 1.2 Hz, 1H). 13C NMR 119.3, 121.6, 125.5, 126.8, 126.9, 128.4, 128.8, 132.9,

PAGE 53

41 134.8, 135.3, 144.8, 150.3, 201.7. Anal. Calcd. For C15H10OS2: C, 66.64; H, 3.73. Found: C, 66.23; H, 3.71.

PAGE 54

42 CHAPTER 4 SYNTHESES AND CHARACTERIZATI ON OF ENERGETI C MATERIALS 4.1 Introduction This chapter is a summary of work completed in collaboration with the US Army on the synthesis and characterization of energeti c materials. Three projects are presented: synthesis and characterization of (i) blowing agents, (ii) hypergolic agents and (iii) dinitro substituted five-m embered heterocycles. 4.1.1 Synthesis and Characteriza tion of Blowing Agents The rubber industry employs blowing agents (gas generating agents), such as dinitropentamethylenetetramine and p -tolysulfonylhydrazide, in the production of microcellular rubber.37 Azodicarbonamide, Exocerol 232, and Hyderocerol BIH are blowing agents that are now commonly used in the plastics industry replacing CFCs to produce polymer foams.38-40 Another significant a pplication of blowing agents is their use in propellant formulations.40-43 In a collaborative effort with the US Army, development of novel munition formulations was investigated. This sub-section details the synthesis and characterization of energetic compounds to provide new blow ing agents. The US Army has previously applied blowing agents (e.g. 2,4dinitrophenylhydrazine) as en ergetic material additives in explosive mixtures to modify general mun ition properties. Inclusion of blowing agents that display separate isotherms from the ot her components in the e xplosive mixture is a method of tempering the violence of the expl osion. For a particular Army formulation containing trinitrotoluene (TNT) and cyclotri methylenetrinitramine (RDX), inclusion of

PAGE 55

43 blowing agents possessing a DSC of ~180 oC provides a means of bursting open any confinement before the reaction of the ma in constituents, thus mitigating cook off violence. Of particular interest are blowing agents with the following characteristics: quick generation of gas, mp higher than 75 oC, stable, and with DSC an alysis that indicates gas evolution at 140–200 oC. Stable blowing agents 4.1–4.4 (utilized in the plastics and rubber industry) are reported to possess th e required melting points and suitable DSCs (Figure 4-1) .39, 84-87 NN O NH2H2N O NMe O NO N O Me NO N H N N N N N N N ON NO (mp 200-206 oC) 4.1 DSC 225 oC (mp 118 oC) DSC 145 oC 4.2 4.3 DSC 195 oC (mp 215 oC) 4.4 DSC 221-243 oC Nitrosan ADCA DNPT PT Figure 4-1. Blowing agents with reported melting points and DSCs. The literature reports syntheses of other energetic additives 4.5–4.7 that possess measurable melting points, but have not been analyzed by TGA analysis (Figure 4-2).88 To obtain TGA data for the evaluation of energetic additives 4.5–4.7 as blowing agents, development of reasonable syntheses that coul d potentially be scaled up to provide 50– 100 g quantities of these compounds was undertaken. Pyrazolium nitrate 4.8 was an accidental discovery in that it was a byproduct in the attempted synthesis of 3,4-

PAGE 56

44 dinitropyrazole. The nitrate salt of pyrazo le was easily obtained from the reaction mixture by recrystallization. This com pound was also thought to be a good blowing agent candidate so testing was conducted on this nitrate salt. 4.8 4.5 4.6 4.7 S O2N N N S O2N N N S O2N N N N N N SO2 NH+NH N+O -O OFigure 4-2. Energetic Additives without reported TGA analysis. 4.1.2 Syntheses of Hypergolic Agents Hypergolic agents are compounds that can be used as fuels and oxidizers which ignite on contact with one another and th erefore do not need a source of ignition.44 These agents have found many uses in rocketry for both manned and unmanned space flight, mainly due to their easy start and restart capability.44 Hypergolic propellants have advantages over other propellants such as cryogenics in that they are easily stored and are relatively inert until they are in contact with the other agent.45 Since hypergolic propellants do not need an ignition source th ey are often the propellant of choice for spacecraft and satellites as they are required to stop and start their engines thousands of times over the design life of the vehicle, thereby eliminating one source of possible failure.45 Hypergolic compounds are employed in liquid bipropellant rocket propulsion systems which consist of gas generators, sepa rate tanks for the stor age of the hypergolic fuel and oxidizer, and lastly the engine. Op eration of the propulsion system begins when

PAGE 57

45 the gas generators have been initiated and the gases from th e gas generator pressurize the fuel tanks. When the oxidizer and fuel valves open, the pressurized oxidizer and fuel tanks force the propellants through the plumbi ng and into the engine. Upon contact with one another the hypergolic fuel and oxidant spontaneously combust through an oxidation reaction thereby creating propulsi on without an ignition source.97 The most common hypergolic fuels currently in use by various space agencies (USA, Russia and China) are hydrazine monomethyl hydrazine (MMH) and unsymmetrical dimethyl hydrazine (UDMH).98 The most common oxidizers are nitrogen tetroxide, inhibited fuming red ni tric acid (IRFNA), nitric aci d, chlorine trifluoride, and concentrated hydrogen peroxide.99 Monomethyl hydrazine MM H and nitrogen tetroxide were used in the core liquid propellant stages of the Titan family of launch vehicles and on the second stage of the Delta rocket. The Space Shuttle orbiter us es hypergolic agents in its Orbital Maneuvering Subsystem (O MS) for orbital insertion, major orbital maneuvers and deorbit.89 Inhibited red fuming nitric acid (IRFNA) type III B, monomethyl hydrazine (MMH) are currently the most common oxidizers for use in bipropellant rocket propulsion systems.99 Traditional hypergolic propellants, such as IRFNA, nitrogen tetroxide, and members of the hydrazine family are very ener getic, but also toxic and/or carcinogenic. Due to these hazards, such propellants are dangerous to people, they are also expensive and hazardous to transport, handle and use. As such, there has been a desire to find nontoxic hypergolic fuels. The US Army is conducting research on suitable replacements for MMH and its derivatives by conduc ting thermal analysis on various tertiary diamines.

PAGE 58

46 In a collaborative effort with the US Army, research was conducted to develop reasonable synthetic routes to the followi ng hypergolic fuels which can potentially be scaled-up to provide 50–100 g qua ntities (Figure 4-3). These potential hypergolic fuels were then shipped to Picatinny arsenal fo r US Army engineers to conduct thermal analysis to be completed in the near future. N N N N N N Me Me N N Me Me Me Me 4.9 4.10 4.11 4.12 Figure 4-3. Hypergolic fuels. Previously 1,3-dimethylhexahydropyrimidine 4.10 and 1,3-dimethylimidazoline 4.9 were synthesized by condensation of the corresponding diamines 4.18 90, 4.2091 with formaldehyde (Scheme 4-1). Stien also reported the synthesis of 1,3-dimethylimidazoline 4.9 by reducing 1,3-dimethylimidazolidin-2-one 4.22 with LAH at room temperature in a yield of 58 % (Scheme 4-1).92 HCOH N N N N N N O HCOH 4.10 LAH, rt ether 4.9 26 % CH3NH(CH2)nNHCH380% (crude) 4.22 4.18 n=3 4.20 n=2 58% Scheme 4-1. Synthesis of 4.10 and 4.9. Dimethyl-(2-pyrrolidin-1-yl-ethyl)amine was previously synthesized by reacting pyrrolidine with 2-chloroN,N -dimethylethanamine hydrochloride to form the desired

PAGE 59

47 product in only 12% yield.95 The yield was too low to scal e up to 50-100 g quantities for the US Army so a novel synthetic strate gy had to be devised (Scheme 4-2). N N NH (CH3)2N(CH2)2Cl HCl 4.11 12% Scheme 4-2. Synthesis of dimethyl-(2-pyrrolidin -1-yl-ethyl)amine 4.11. 4.1.3 Synthesis of Dinitro-Substitu ted Five Membered Heterocycles Dinitro derivatives of five-membered hetero cycles may be of interest as energetic materials and/or possible blowing agent candida tes. They have also been shown to have diverse biological activity, for example 2,4-dinitroimidazole de rivatives have been shown to be very effective agents in increasing the sensitivity of hypoxic ce lls toward irradiation in cancer radiotherapy.46 Numerous dinitro heterocycles have also been shown to be useful intermediates, for instance Padwa r ecently converted dinitrofuran to various polysubstituted phenols through SnAr nucleophilic substitution reactions.47 The aim of the present work is the devel opment of reasonable syntheses of dinitro substituted five-membered heterocyclic compounds. Literature methodologies for the general preparation of dinitro substituted fi ve-membered heterocycles are scarce. Several literature examples based on direct nitration of heterocyclic rings re sult in mixtures of isomers, which are often difficult to separate.93a,b 4.2 Results and Discussion 4.2.1 Results Syntheses and Charact erization of Blowing Agents Various 2-substituted benzo[1,2,3,4]thiatriazi ne-1,1-dioxides 4.5-4.7 were prepared following a procedure by Ullmann et al. star ting from 2-nitrosulfonyl chloride (4.13) (Schemes 4-3, 4-4, 4-5).88

PAGE 60

48 Synthesis of 2-phenylbenzo[ 1,2,3,4]thiatriazine-1,1-dioxide 4.5 was carried out starting from 2-nitrosulfonyl chloride ( 4.13 ) (Scheme 4-3). Condensation of the sulfonyl chloride with phenylamine gave sulfonamide 4.14a in 82 % yield. Baeyer reduction of the nitro group provided 2-aminoN -phenylbenzenesulfonamide ( 4.15a) in 92 % yield, which was then cyclized to 2-pheny lbenzo[1,2,3,4]thiatriazine-1,1-dioxide 4.5 in 75 % yield by reaction with HONO generated in-situ. SO2N N N Ph SO2Cl NO2 Ph-NH2SnCl2, HCl SO2HN NH2Ph SO2HN NO2Ph pyridine HCl, NaNO24.13 4.14a 4.5 EtOH 4.15 a Scheme 4-3. Synthesis of 2-phenylbenzo[ 1,2,3,4]thiatriazine-1,1-dioxide 4.5 Similarly, 4.6 was prepared in 74 % yield by cyclization of 4.15b with HONO. (Scheme 4-4). Sulfonamide 4.14b was prepared in 70 % yield by the reaction of 2nitrosulfonyl chloride ( 4.13 ) with mesitylamine. SO2N N N Me Me Me SnCl2, HCl SO2H N NH2Me Me Me SO2H N NO2Me Me Me pyridine HCl, NaNO24.13 4.6 4.14b 4.15b mesitylamine EtOH SO2Cl NO2 Scheme 4-4. Synthesis of compound 4.6 Bis-benzo[1,2,3,4]thiatriazine-1,1-dioxide 4.7 was obtained in 68 % yield from 4 15c (Scheme 4-5). Two equivalents of sulfonyl chloride 4.13 were reacted with

PAGE 61

49 ethylenediamine to give sulfonamide 4.14c in 93% yield. Upon reduction, sulfonamide 4.14c provided 4.15c in 92 % yield, which was cyc lized with HONO to provide 4.7 4.7 HCl, NaNO24.13 4.14c 4.15c 2 SO2Cl NO2 H2N NH2 Et3N S O2 NO2 H N N H O2S NO2 S O2 NH2 H N N H O2S NH2 O2S N NN N N N S O2 Scheme 4-5. Synthesis of bis-be nzo[1,2,3,4]thiatriazine-1,1-dioxide 4.7 TGA analysis (50oC to 300 oC, rate: 20 oC/min.) of benzo[1,2,3,4]thiatriazine-1,1dioxides ( 4.5 1.545 mg; 4.6 0.783 mg; 4.7 0.345 mg) showed a trend of gradual decomposition (Figure 4-4). 2-Phen ylbenzo[1,2,3,4]thiatriazine-1,1-dioxide 4.5 showed the sharpest loss in mass, losing 30% from 210 oC to 265 oC. While 4.7 steadily decomposed, 4.6 decomposed in stages starting from 100 oC with plateaus from 110– 130 oC and 140–190 oC. Compound 4.5 is the most promising among this series ( 4.5-4.7 ), since it demonstrated the sharpest decomposition. Unfortunately it was found that upon stori ng at room temperature for extended periods of time compounds 4.5-4.7 decomposed into complex mixtures. Since blowing agents must be stored in munitions casi ngs under diverse temperature ranges these compounds would be of no use a energetic additives. Originally pyrazolium nitrate 4.8 was formed as a byproduct in the attempted dinitration of pyrazole from a previous route established in the Katritzky group.94 Upon adding ethyl acetate to the reaction mixture it was found that small microcrystals formed, and NMR, CHN analysis and X-ray crys tallography showed that the byproduct was pyrazolium nitrate. Unfortunately it was al so found that the react ion between pyrazole

PAGE 62

50 4.16 and concentrated nitric ac id in trifluoroacetic anhydr ide gave an inter-chelating molecular complex of 4-ni tropyrazole and oxalic acid 4.17 not 3,4-dinitropyrazole (Scheme 4-6). Figure 4-4. TGA analysis of compounds 4.5-4.7. N H N TFAA HNO3NH+H N + NH+H N O2N +HN H N NO2 O O HO OH 4.16 4.8 4.17NO 3 Scheme 4-6. Synthesis of inter-chelating molecu lar complex of 4-nitropyrazole and oxalic acid 4.17 This result is consistent with CHN data (Calcd for C8H8N6O8: C, 30.39; H, 2.55; N, 26.58. Found: C, 30.54, H, 2.72; N, 30.85), and X -ray analysis which shows that the structure is a complex of 2 molecules of 4nitropyrazole and 1 molecule of oxalic acid (Figure 4-5). It is believed that oxalic acid arises from the hydrolysis of trifluoroacetic acid.

PAGE 63

51 Figure 4-5. X-ray of molecular comple x of 4-nitropyrazole and oxalic acid 4.17 While this result was not expected it was believed that pyrazolium nitrate could be a viable blowing agent candidate. TGA analysis of 1.4052 mg of the pyrazolium nitrate 4.8 showed a decline in mass before 160 oC. Thus it is not a good candidate for th e specifications of a blowing agent, although it may be suitable for other Army appli cations (Figure 4-6). The calculated heat flow for the nitrate salt is +0.35 W/mmol. NH+H N NO3Figure 4-6. TGA and DSC analysis of pyrazolium nitrate 4.8.

PAGE 64

52 4.2.2 Results Synthesis of Hypergolic Agents The first attempted synthesis of 1,3-dimethylhexahydropyrimidine 4.10 was achieved in 72% yield by the treatment of NmethylN -[3-(methylamino)propyl]amine 4.18 with formaldehyde 4.19 in water at room temperature for 18 h (Scheme 4-7). H N NH Me Me HCOH N N Me Me + 4.18 4.19 4.10 H2O RT, 18 h Scheme 4-7. Synthesis of cyclic aminal 4.10 from formaldehyde. While this methodology worked well it us ed the relatively expensive reagent NmethylN -[3-(methylamino)propyl]amine. These reaction conditions also failed to produce 1,3-dimethyl-imidazoline 4.9 when N,N -dimethylethane-1,2-diamine 4.20 was reacted with formaldehyde 4.19 (Scheme 4-8). NH NH Me Me HCHO + 4.20 4.19 4.9 H2O RT, 18 h N N Me Me Scheme 4-8. Synthesis of cyclic aminal 4.9 from formaldehyde. Another methodology for the preparation of 1,3-dimethylhexahydropyrimidine 4.10 by the reduction of 1,3-dimet hyltetrahydropyrimidin-2-one 4.21 with 1.15 equivalents of LAH in ether under reflux for 12 h afforded a 99 % yield. This provided a cheap source of starting material (1,3-dime thyltetrahydropyrimidin-2-one 4.21 ) and better conditions for isolation of the desired product by simply evaporating ether under reduced pressure (Scheme 4-9). The conditions established by Jo hannes and Turid in which the cyclic urea 4.21 was reduced with LAH at room temper ature gave a complex mixture, perhaps

PAGE 65

53 because LAH oxidized before the reaction c ould take place or it was not soluble enough at room temperature.90 NN Me Me O + 1.15 LAH Diethyl Ether Reflux, 12 h NN Me Me 4.10 4.21 Scheme 4-9. Synthesis of cyclic aminal 4.10 via reduction with LAH. This methodology also reduced 1,3dimethylimidazolidin-2-one 4.22 into 1,3dimethyl imidazoline 4.9 in 80% yield (Scheme 4-10). + 1.15 LAH Diethyl Ether Reflux, 12 h N N Me Me O N N Me Me 4.9 4.22 Scheme 4-10. Synthesis of cyclic aminal 4.9 via reduction with LAH. N,N -Dimethyl-2-(1-pyrrolidinyl)-1-ethanamine 4.11 was obtained by the reaction of 2.3 equivalents of LAH and 1[2-(dimethylamino)ethyl]dihydro-1 H -pyrrole-2,5-dione 4.25 in ether under reflux for 12 h in 87 % yield. Intermediate 4.25 was prepared by treatment of succinic anhydride 4.23 with dimethylaminoethylamine 4.24 in a microwave synthesizer at 100 watts and 130 oC for 5 minutes followed by distillation to give the product 4.25 in 39 % yield (Scheme 4-11). This methodology was superior to the previous literature method established by Ri ed who reacted pyrrolidine with 2-chloroN,N -dimethylethanamine hydrochlorid e to obtain only a 12% yield.95 N N Me Me O O N N Me Me O O O H2N N Me Me LAH, ether 4.11 4.25 Reflux, 12 h 4.23 4.24 Scheme 4-11. Synthesis of N,N -dimethyl-2-(1-pyrrolidinyl)-1-ethanamine 4.11

PAGE 66

54 1,3-(Dipyrrolidyl)propane 4.12 was prepared in 43% yi eld by the reaction of 4 equivalents pyrrolidine 4.26 with 1,3-dibromopropane 4.27 using a procedure by Gero (Scheme 4-12).96 H N BrBr N N + benzene 24 h, rt 4 h, reflux 4.12 4.26 4.27 4 Scheme 4-12. Synthesis of 1,3-(dipyrrolidyl)propane 4.12. 4.2.3 Results Nitration of Five Membered Heterocycles The direct dinitration of 2-ethylthiophene 4.28 was accomplished with HNO3 in TFAA at 0 oC for 12 h. It was found that this reac tion proceeds regioselectively to the desired dinitro derivative 4.29 in a yield of 37% (Scheme 4-13). S S NO2O2N HNO3TFAA 4.28 4.29 Scheme 4-13. Synthesis of 2-ethyl-3,5-dinitrothiophene 4.29 Attempts to extend the standard react ion conditions for dinitration of 2bromothiophene gave a complicated mixtur e of nitro substituted derivatives. The commercially available mixture of 2and 3-mononitrothiophenes 4.30-4.31 was reacted with ammonium nitrate in trifluoroacetic a nhydride at room temperature for 16 h to yield a mixture of 2,44.32 and 2,5-dinitrothiophenes 4.33 in high yield (91%). Analysis of the 1H NMR spectra for the mixture showed a singlet at 7.27 which is characteristic for 2,5-dinitrothiophene and a doublet of doublets characteristic for 2,4-dinitrothiophene at 8.44. Integration of these two peaks gave a ratio of 1.5:1 for 2,4-di nitrothiophene and 2,5-dinitrothiophene. The mixture melts at 53.1-54.0 oC and might be a good candidate as an energetic additive (Scheme 4-14).

PAGE 67

55 S NO2 S NO2 S NO2O2N S O2NNO2 NH4NO3+ + TFA, TFAA ratio 6 :1 ratio 1.5 :1 overall yield 91% 4.30 4.32 4.33 4.31 Scheme 4-14. Synthesis of mixture of 2,44.32 and 2,5-dinitrothiophenes 4.33. 4.3 Conclusion This chapter summarizes the work accomplished in collaboration with the US Army on the synthesis and characterization of broadly defined energetic materials. The work on blowing agents included thermogravim etric analysis in order to gauge their usefulness as blowing agents, unfortunately none of the synthesized agents were applicable as blowing agents due to either being unst able at room temperature 4.5-4.7 or undergoing undesirable thermal decomposition profiles 4.8 Four hypergolic compounds 4.9-4.12 were synthesized and the methodologies used for compounds 4.9-4.11 improved upon the previous literature methods by providi ng higher yields and easier isolation of the compounds. Dinitration of five member ed rings is preliminary work but the two examples listed have the advantage of being simple, one step pro cedures with yields ranging from moderate to excellent. More exam ples of di-nitrosubst ituted five membered heterocycles are planned for synthetic study in the future. 4.4 Experimental Caution! Although we have not experienced any problems in synthesizing or handling these compounds, proper safety precautions should be followed and these materials should be treated with extreme care. Melting points were determined using a Br istoline hot-stage microscope and are uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a 300

PAGE 68

56 MHz NMR spectrometer in DMSOd6 or chloroformd solution as indicated. THF was distilled from sodium-benzophenone ketal pr ior to use. Column chromatography was performed on silica gel (300–400 mesh). Elemental analyses were performed on a Carlo Erba-1106 instrument. For the DSC and T GA experiments a Perkin Elmer DSC 7 or Perkin-Elmer TGA 7 were used to analyze samp les (~3 mg) with a heating rate of 10 or 20 oC/min in an argon atmosphear with a flow rate of 50 mL/min. Thermal calibrations for differential scanning calorimetry were made using indium and freshly distilled n octane as references. Heats of fu sion were referenced against indium. 4.4.1 General Procedure for the Prepar ation of Benzo[1,2,3,4]thiatriazine-1,1dioxides 4.5-4.6 Sodium nitrite (0.36 g, 5.2 mmol) was added to a stirred solution of the corresponding sulfonamide (3.5 mmol) dissol ved by gentle warming in aqueous acetic acid 95% (50 mL) and then cooled to 25 oC. The resulting mixture was stirred at 25 oC for 8 hours, then ice-cold water (200 mL) was added a nd the precipitated product was filtered and washed with water. The red solid was dried in vacuo overnight to afford a 75% yield of 2-phenyl-2 H -benzo[1,2,3,4]thiatriazine-1,1dioxide and 74% of 2-(2,4,6Trimethyl-phenyl)-2H-benzo[1,2,3,4] thiatriazine-1,1-dioxide. 2-Phenyl-2 H -benzo[1,2,3,4]thiatriazine-1,1-dioxide (4.5) Red microcrystals (75%) mp 101.0oC, (Lit. mp 111 oC).52 1H NMR 7.98–8.03 (m, 2H), 7.54–7.59 (m, 1H), 7.39–7.44 (m, 1H), 7.29–7.34 (m, 1H), 7.03–7.25 (m, 3H).13C NMR 135.5, 132.5, 128.4, 130.4, 129.1, 125.4, 125.3, 125.0, 122.1, 120.6. 2-(2,4,6-Trimethylphenyl)-2 H -benzo[1,2,3,4]thiatriazine-1,1-dioxide (4.6) Red microcrystals (74%) mp 151.0 oC, (Lit. mp 150 oC).52 1H NMR 8.09–8.14 (m, 1H),

PAGE 69

57 7.91–7.96 (m, 1H), 7.80–7.86 (m, 1H), 2.35 (s, 3H), 2.29 (s, 6H). 13C NMR 141.5, 140.7, 138.9, 134.0, 132.8, 130.3, 129.8, 127.7, 129.6, 120.6, 21.1, 18.3. 4.4.2 General Procedure for the Prepar ation of Pyrazolium Nitrate 4.8 Trifluoroacetic anhydride [6.5 mL] was added to 1-H pyrazole [ 0.68 g,10 mmol] under vacuum and chilled in an ice bath. C oncentrated nitric acid [2.2 mL] was added 0.5 mL increments very slowly (~45 minutes) to the mixture. After stirring for 12 h at room temperature, ethyl acet ate (50 mL) was added to the reaction mixture and then stored in freezer 3 hours until the byproduct prec ipitated out as white crystals which were then filtered off. Note: this was step wa s repeated as necessary until no byproduct was evident after freezing the mixture. (0.65 g, Yield=50%) precipitated off as white microcrystals. Pyrazolium nitrate (4.8) White microcrystals (50%). 1H NMR 8.59 (s, 1H), 12.21 (s, 1H). 13C NMR 32.5, 134.1, 135.5. 4.4.2.1 General Procedure for the Preparat ion of Hypergolic Aminals 4.9 and 4.10. The corresponding cyclic urea (16.8 mmol) wa s added dropwise to a solution of LAH (0.80g, 19.2 mmol) in diet hyl ether (160 mL). The mixture was then refluxed gently for 12 hr. Water (5mL) was added slowly then 2N NaOH (2mL) solution was added dropwise to quench the reaction. The so lid was then filtered off and diethyl ether was removed under reduced vacuum to afford 1,3-dimethylimidazolidine (1.46 g) in a yield of 80% and 1,3-dimethylhexahydropyr imidine (1.91 g) in a yield of 99%. 1,3-Dimethylimidazolidine (4.9) Clear oil (80%) bp 111 oC/760 mm Hg, (lit bp 110 oC/760 mm Hg).57 1H NMR 2.25 (s, 6H), 2.63 (s, 4H), 3.15 (s, 2H). 13C NMR 41.5, 54.3, 79.8.

PAGE 70

58 1,3-Dimethylhexahydropyrimidine (4.10) Clear oil (99%) bp 131 oC/760 mm Hg, (lit bp 126 oC/760 mm Hg).56 1H NMR 1.69 (m, 2H), 2.24 (s, 6H), 2.40-2.43 (m, 4H), 2.97 (br s, 2H). 13C NMR 23.9, 43.1, 54.1, 79.6 4.4.2.2 General Procedure for the Preparatio n of Hypergolic Agent Dimethyl(2pyrrolidin-1-yl-ethyl)amine 4.11 1-(2-Dimethylaminoethyl)pyrrolidine2,5-dione (4g, 23.5 mmol) was added to a solution of LAH (2.04g, 54.05 mm ol) in ether. The mixt ure was refluxed overnight under nitrogen then the mixture was quenche d with water and the organic layer was filtered off. Ether was removed under reduced pressure to afford dimethyl-(2-pyrrolidin1-yl-ethyl)amine (2.91 g) in a yield of 87%. N,N -Dimethyl-2-(1-p yrrolidinyl)-1-ethanamine (4.11) Clear oil (87%) bp 170.9 oC/760 mm Hg, (lit bp 56.5 oC/1.5 mm Hg).64 1H NMR 1.70-1.74 (m, 4H), 2.19 (s, 6H), 2.35-2.40 (m, 2H), 2.47-2.54 (m, 6H). 13C NMR 21.4, 43.9, 52.32, 52.34, 56.5. 4.4.2.3 General Procedure for the Prep aration of Hypergolic Agent 1,3(Dipyrrolidyl)propane 4.12 To a solution of 1,3-dibromopropane ( 8.35 mL, 21 mmol) and dry benzene (200 mL) was added pyrrolidine (27.02 mL, 84 mmol). The reaction mixture was stirred at room temperature for 12 hours then the mi xture was refluxed for 4 hours on a hot water bath, cooled and filtered from pyrrolidine bromide. Benzene was removed under reduced vacuum to afford 1,1'-(1,3-propanedi yl)bis-pyrrolidine (6.5g, 43% yield). 1,3-(dipyrrolidyl)propane (4.12) Clear oil (43%) bp 111oC/760 mm Hg, (lit bp 110 oC/760 mm Hg).65 1H NMR 1.70-1.70 (m, 10H), 2.45-2.50 (m, 12H). 13C NMR 23.5, 28.8, 54.4, 55.0.

PAGE 71

59 4.4.3 General Procedure for the Preparation of 2-Ethyl-3,5-Dinitrothiophene 4.29 Trifluoroacetic anhydride (2.9 mL) was added to 2-ethylthiophene (0.56 mL, 5 mmol) under vacuum and chilled in an ice bat h. Concentrated nitric acid (0.88 mL) was added in 0.3 mL increments very slowly (~45 minutes) to the mixture. After stirring for 12 h at room temperature, ethyl acetate ( 50 mL) was added to the reaction mixture and the organic layer was washed with brine and the organic layer was extracted. Purification by column chromatography gave 2-ethyl-3,5dinitrothiophene ( 0.29 g, 37% yield) as a red oil. 2-Ethyl-3,5-dinitrothiophene (4.29) Red oil (37%). 1H NMR 1.48 (t, J =7.5 Hz, 3H), 3.39 (dd, J =7.5 Hz, 2H), 8.36 (s, 1H). 13C NMR 13.8, 23.8, 124.5, 141.3, 145.4, 157.4. Anal. Calcd for C6H6N2O4S: C 35.64, H2.99, N 13.86. Found C 35.82, H 2.83, N 13.57. 4.4.4 General Procedure for the Prepar ation of 2,4-Dinitrothiophene 4.32, 2,5Dinitrothiophene 3.33 Pure 2-nitrothiophene (0.5g, 3.9 mmol) was added dropwise to a solution of NH4NO3 (0.62g, 3.9 mmol) in TFA (1.2 mL) and TFAA (1.1 mL) at 0 oC. The reaction mixture was allowed to warm to room temper ature and was stirred for 12 hr. Water was added to the reaction mixture and the product was filtered off with gravity filtration to give a mixture of 2,4-dinitrothiophene and 2,5-dinitrothiophene (0.94 g, 91%). 2,4-dinitrothiophene (4.32), 2,5-dinitrothiophene (4.33) (mp 53.1-54.0 oC) 1H NMR 7.27 (s, 1H), 7.87 (s, 1H), 8.44 (dd, J 1=1.8, 10.5 Hz, 1H). Anal. Calcd for C4H2N2O4: C 27.59, H 1.16, N 16.09. Found C 28.02, H 0.96, N 15.68.

PAGE 72

60 CHAPTER 5 CONCLUSION The successful application of 1 benzotriazolyl-2-propynones as a novel 1-3biselectrophile was demons trated in Chapter 2. 1 Benzotriazolyl-2-propynones, in comparison with the literature pro cedures to synthesize pyrido[1,2a ]pyrimidin-2-ones, offered shorter reaction times, cleaner c onversion to products, and higher yields. 1 Benzotriazolyl-2-propynones were also su ccessfully reacted with other 1,3-bisnucleophiles: 2-picolines, 2-methylquino line and 2-aminothiazole to form 2 H -quinolizin2-ones, pyrido[1,2a ]quinolin-3-ones, and thiazolo[3,2a ]pyrimidin-7-one in moderate to excellent yields. Several novel thioacyl nitrobenzotriazoles, which were synthesized from a previous procedure from Rapoport, were shown to be e ffective thioacylating r eagents and a viable alternative to previous problematic routes. This procedure was compared in conjunction with another procedure which used a Grigna rd methodology for the synthesis of thioacyl benzotrizoles. It was found th at the Grignard method is th e preferred means of obtaining arylthiocarbonylbenzotriazoles, while Rapoport’s synthesis is preferred for alkyl, alkynyl, and heteroaryl thiocarbonylbenz otriazoles. To test the thio acylating ability of the new thioacyl nitrobenzotriazoles synthesized, seve ral were reacted with 1-naphthalenol to form novel thionoesters. Advantages of th ioacyl nitrobenzotriazo les are that they circumvent the use of unstable or hazardous reagents, the mild conditions employed are tolerable of a large variety of functional groups and yields are comparable and in many cases higher than previo usly reported methods.

PAGE 73

61 Chapter 4 summarizes the work accomplished in collaboration with the US Army on the synthesis and characterization of broadl y defined energetic materials. The work on blowing agents included thermogravimetric analysis in order to gauge their usefulness as blowing agents, unfortunately none of th e synthesized agents were applicable as blowing agents, due to either being unst able at room temperature or undergoing undesirable thermal decomposition profile s. Four hypergolic compounds were synthesized and the methodologies used fo r three of the compounds improved upon the previous literature methods by providing hi gher yields and easier isolation of the compounds. Dinitration of five-membered rings is preliminary work, but the two examples listed have the advantage of bei ng simple, one-step procedures with yields ranging from moderate to excellent. More ex amples of dinitrosubstituted five-membered heterocycles are planned for synthetic study in the future

PAGE 74

62 LIST OF REFERENCES 1. Katritzky, A.R.; Belyakov Aldchim. Act. 1998 31(2) 35. 2. Katritzky, A.R.; Lan, X.; Yang J.Z. Chem. Rev. 1998 98 409. 3. Reboud, R. M. J. Am. Chem. Soc. 1980 102(3) 1039 4. a) Katritzky, A. R.; Yannakopoulou, K. ; Lue, P.; Rasala, D.; Urogdi, L. J. Chem. Soc., Perkin Trans. 1 1989 225. b) Katritzky, A. R.; Pernak, J.; Fan, W.-Q.; Saczewski, F. J. Org. Chem. 1991 56 4439.c) Katritzky, A. R.; Urogdi, L.; Mayence, A. J. Chem. Soc., Chem. Commun. 1989 337. d) Katritzky, A. R.; Takahashi, I.; Fan, W.-Q.; Pernak, J. Synthesis. 1991 1147. e) Katritzky, A. R.; Fan, W.-Q.; Black, M.; Pernak, J. J. Org. Chem. 1992 57 547. 5. a) Katritzky, A. R.; Long, Q.-H.; Lue, P.; Jozwiak, A. Tetrahedron 1990 46 8153. b) Katritzky, A. R.; Long, Q.-H.; Lue, P. Tetrahedron Lett 1991 32 3597. c) Katritzky, A. R.; Lan, X.; Zhang, Z. J. Heterocycl. Chem. 1993 30 381. d) Katritzky, A. R.; Barcock, R. A.; Long, Q. -H.; Balasubramanian, M.; Malhotra, N.; Greenhill, J. V. Synthesis 1993 233. e) Katritzky, A. R.; Jiang J. J. Org. Chem. 1995 60 7597. 6. Katritzky, A. R.; Kuzmierkiewicz, W. J. Chem. Soc., PerkinTrans. 1 1987 819. b) Katritzky, A. R.; Yang, Z.; Lam, J. N. J. Org. Chem. 199 1, 56 ,2143. c) Richard, J. P.; Nagorski, R. W.; Rudich, S.; Amyes, T. L.; Katritzky, A. R.; Wells, A. P. J. Org. Chem. 1995 60 5989. d) Katritzky, A. R.; Yang, Z.; Lam, J. N. Synthesis 1990 666. e) Katritzky, A. R.; Jiang, J. J. Org. Chem. 1995 60 7597 7. Graebe, C.; Ullmann, F. Justus Liebigs Ann. Chem 1896 291 16. 8. Katritzky, A. R.; Kuzmierkiewicz, W.; Greenhill, J. V. Recl. Trav. Chim. Pays-Bas 1991 110 369. 9. Katritzky, A. R.; Shobana, N.; Pernak, J.; Afridi, A. S.; Fan, W.Q. Tetrahedron 1992 48 7817. 10. Katritzky, A. R.; Perumal, S.; Fan, W.-Q. J. Chem. Soc., Perkin Trans. 2 1990 2059. 11. Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Org. Chem 1989 54 6022. 12. Katritzky, A. R.; Blitzke, T.; Li, J. Synth. Commun. 1996 26 3773.

PAGE 75

63 13. Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Chem. Soc. Perkin Trans 1 1987 791. 14. Katritzky, A. R.; Rachwal, S.; Offerm an, R. J.; Najzarek, Z.; Yagoub, A. K.; Zhang, Y. Chem. Ber 1990 123 1545. 15. Bachman, G. B.; Heisey, L. V. J. Am. Chem. Soc. 1946 68 2496. 16. Katritzky, A. R.; Jurczyk, S.; Bogumila R.; Stanislaw, R.; Shcherbakova, I., Yannakopoulou, K. Synthesis 1992 12 1295 17. Katritzky, A. R.; Wu, J.; Kuzmierkiewicz, W.; Rachwal, S. Liebigs Ann. Chem 1994 1. 18. Katritzky, A. R.; Rachwal, S.; Caster, K. C.; Mahni, F.; Law, K. W.; Rubio, O. J. Chem. Soc., Perkin Trans. 1 1987 781. 19. Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Org. Chem. 1994 59 5206. 20. Katritzky, A. R.; Zhang, G.; Jiang, J. J. Org. Chem. 1995 60 7625. 21. Rees, C. W.; Storr, R. C. J. Chem. Soc. (C) 1969 1478. 22. Katritzky, A. R.; Li, J.; Malhotra, N. Liebigs Ann. Chem. 1992 843. 23. Azolides, Organic Synthesis And Biochemistry ; Baur, H.; Stabb, K.H.; Scneider, K.M., Eds.; John Wiley and Sons Ltd: New York, 1998. 24. Katritzky, A. R.; Shobana, N.; Pernak, J.; Afridi, A. S.; Fan, W. Q. Tetrahedron 1992 48 7817. 25. a) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org. Chem. 2000 65 8210. b) Katritzky, A. R.; Chang, H.-X.; Yang, B. Synthesis 1995 503. c) Katritzky, A. R.; Yang, B.; Semenzin, D. J. Org. Chem. 1997 62 726. d) Katritzky, A. R.; Pastor, A.; Voronkov, M. V. J. Heterocycl. Chem. 1999 36 777. e) Katritzky, A. R.; Pastor, A. J. Org. Chem. 2000 65 3679.Katritzky, A.R.; Suzuki, K.; Wang Z. SynnLett 2005 1656. 26. Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003 2795. 27. Katritzky, A.R.; Suzuki, K.; Wang Z. SynnLett 2005 1656. 28. Katritzky, A. R.; Shestopalov, A. A.; Suzuki, K. Synthesis 2004 1806. 29. Katritzky, A. R.; Suzuki, K.; Singh, S. K. J. Org. Chem. 2003 68 5720. 30. Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003 68 4932. 31. Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003 68 1443.

PAGE 76

64 32. Katritzky, A. R.; Wang, Z.; Wang, M.; Wilkerson, C. R.;Hall, C. D.; Akhmedov, N. G. J. Org. Chem. 2004 69 6617. 33. Katritzky, A. R.; Ledoux, S.; Witek, R. M.; Nair, S. K. J. Org. Chem. 2004 69, 2976. 34. Larsen, C.; Steliou, K.; Harpp, D. N. J. Org. Chem 1978 43 337. 35. Katritzky, A. R.; Witek R.M.; Rodriguez-Garc ia V.; Mohapatra P. P.; Rogers J. W.; Cusido J.; Abdel-Fattah A. A. A.; Steel P. J. J. Org. Chem. 70 7866, 2005 36. a) Shalaby, M. A.; Rapoport, H. J. Org. Chem. 1999, 64, 1065. b) Shalaby, M. A.; Grote, C. W.; Rapoport, H. J. Org. Chem. 1996, 61 9045. 37. Kok, C. M.; Tok, I. F.; Toh, H. K. Plastics and Rubber Processing and Applications 1985, 5 281-4. 38. Prasad, A.; Shanker, M. Cellular Polymers 1999 18 35-51. 39. Kim, Kwan-Eung; Lee, Keun-Won. Hwahak Konghak 2002 40 427-430. 40. Marrucho, I. M.; Oliveira, N. S.; Dohrn, R. J. Chem. Eng. Data 2002, 47, 554558. 41. Krabbendam-La Haye, E. L. M.; de Klerk, W. P. C.; Miszczak, M.; Szymanowski, J. Journal of Thermal Analysis and Calorimetry 2003 72 931-942. 42. Niu, Fushui; Ou, Yuxiang; Chen, Boren. Hanneng Cailiao 1997 5 153-156. 43. Ou, Yuxiang; Chen, Boren; Yan, Hong; Ji a, Huiping; Li, Jianjun; Dong, Shuan. Journal of Propulsion and Power 1995 11 838-47. 44. Grinter, K. (August, 2002). NASA Facts. Retrieved from http://wwwpao.ksc.nasa.gov/kscpao/nasafact/count2.htm Last accessed September 2005. 45. Schooley, M. (n.d.). Fuel Propellants St orable, and Hypergol ic vs. Ignitable. Retrieved from http://www.permanent.com/t-mikesc.htm Last accessed September 2005. 46. Agrawal, K.C.; Bears, K.B.; Sehgal, R.K. J. Med. Chem. 1979 22 589. 47. Padwa, A.; Waterson, A. G. ARKIVOC 2001 (iv) 29. 48. Harriman, G. C. B.; Chi, S.; Zhang, M.; Crowe, A.; Bennett, R. A.; Parsons, I. Tetrahedron Lett 2003, 44 3659.

PAGE 77

65 49. a) Smith, R. L.; Barette, R. J.; Sanders-Bush, E. J. Pharmacol. Exp. Ther. 1995 275, 1050. b) Awouters, F.; Vermeire, J.; Smeyers, F.; Vermote, P.; Van Beek, R.; Niemegeers, C. J. E. Drug Dev. Res 1986 8 95. c) Matsutani, S.; Mizushima, Y. Chem. Abstr. 1990 112 98557. d) Yanagihara, Y.; Kasai, H.; Kawashima, T.; Shida, T. Jpn. J. Pharamacol 1988 48 91. 50. a) Hermecz, I.; Kokosi, J.; Podanyi, B.; Liko, Z. Tetrahedron 1996 52 7789. b) Ferrarini, P.; Mori, C.; Primofiore, G.; Calzolari, L.; J. Heterocyclic Chem 1990 27 881. c) Selic, L.; Strah, S.; Toplak, R.; Stanovnik, B. Heterocycles 1998 47 1017. d) Selic, L.; Stanovnik, B. J. Heterocyclic Chem 1997 34 813. e) Ye, F.-C.; Chen, B.-C.; Huang, X. Synthesis 1989 4 317. 51. Dorokhov, V. A.; Baranin, S. V.; Dib, A.; Bogdanov, V. S.; Yakovlev, I. P.; Stashina, G. A.; Zhulin, V. M. Chem. Abstr. 1991 114 101911. 52. Roma, G.; DiBraccio, M. B.; Albi, A.; Mazzei, M.; Ermili, A. J. Heterocyclic Chem 1987 24 329. 53. Al-Jallo, H. N.; Al-Biaty. I. A. J. Heterocyclic Chem 1978 15 801. 54. Acheson, R. M.; Wallis, J. D. J. Chem. Soc., Perkin Trans. 1 1982 1905. 55. Doad, G. J. S.; Okor, D. I.; Scheinmann, F.; Bates, P. A.; Hursthouse, M. B. J. Chem. Soc., Perkin Trans 1 1988 2993. 56. Suri, O. P.; Suri, K. A.; Gupta, B. D.; Satti, N. K. Synth. Commun 2002 32 741. 57. Kato, T.; Atsumi, T. Chem. Abstr. 1968 68 49422g. 58. Murthi, G. S. S.; Gangopadhyay, S. K. Indian J. Chem 1979 17 20. 59. Wahe, H.; Mbafor, J. T.; Nkengfack, A. E.; Fomum, Z. T.; Cherkasov, R. A.; Sterner, O.; Doepp, D. ARKIVOC 2003 ( xv) 107. 60. Nicolaou, K. C.; Sato, M.; Theodorakis, E. A.; Miller, N. D. J.Chem. Soc., Chem. Commun. 1995 1583. 61. Barrett, A. G. M.; Lee, A. C. J. Org. Chem. 1992 57 2818. 62. Baxter, S. L.; Bradshaw, J. S. J. Org. Chem. 1981 46 831. (b) Bradshaw, J. S.; Jones, B. A.; Gebhard, J. S. J. Org. Chem. 1983 48 1127. (c) Jones, B. A., Bradshaw, J. S.; Brown, P. R.; Christensen, J.J.; Izatt, R. M. J. Org. Chem. 1983 48 2635.

PAGE 78

66 63. (a) Baldwin, S. W.; Haut, S. A. J. Org. Chem. 1975 40 3885. (b)Tsurugi, J.; Nakao, R.; Fukumoto, T. J. Am. Chem. Soc. 1969 91 4587. (c) Nagata, Y.; Dohmaru, T.; Tsurugi. J. J. Org. Chem. 1973 38 795. (d) Pettit, G. R.; Piatak, D. M. J. Org. Chem. 1962 27 2127. (e) Maione, A. M.; Torrini, I. Chem. Ind. 1975 839. (f) Kraus, G. A.; Frazier, K. A.; Roth, B. D.; Taschner, M. J.; Neuenschwander, K. J. Org. Chem. 1981 46 2417. 64. Bunnelle, W. H.; Mckinnis, B. R.; Narayanan, B. A. J. Org. Chem. 1990 55 768, and references therein. 65. Reynaud, P.; El Hamad, Y.; Davrinche, C.; Nguyen-Tri-Xuong, E.; Tran, G.; Rinjard, P. J. Heterocycl. Chem 1992 29 991. 66. Kraemer, I.; Schunack, W. Arch. Pharm. (Weinheim, Ger.) 1986 319 1091. 67. Bhattacharya, B. K.; Singh, H. H.; Yadav, L. D. S.; Hoornaert, G. Acta Chim. Acad. Sci. Hung. 1982 110 133. 68. Meijs, G. F.; Rizzardo, E.; Le, T. P. T.; Chen, Y. Makromol. Chem. 1992 193 369. 69. Nielson, D. G. In The Chemistry of Amidines and Imidates ; Patai, S., Ed.; Wiley: New York, 1975; pp 385-489. 70. (a) Vinkler, P.; Thimm, K.; Voss, J. Liebigs Ann. Chem 1976 2083. (b) Voss, J.; Schmueser, W.; Schlapkohl, K. J. Chem. Res. S (Synopses) 71. (a) Hoffmann, R.; Hartke, K. Chem. Ber. 1980 113 919. (b) Kaloustian, M. K.; Nader, R. B. J. Org. Chem. 1981 46 5050. (c) Kantlehner, W.; Haug, E.; Farkas, M. Liebigs Ann. Chem 1982 1582.(d) Nader, R. B.; Kaloustian, M. K. Tetrahedron Lett. 1979 20 1477. 72. Kaloustian, M. K.; Khouri, F. Tetrahedron Lett. 1981 22 413. 73. (a) Hedgley, E. J. Brit. Pat. 1,589,128; 7 May 1981.(b) Adiwidjaja, G.; Gu¨ nther, H.; Voss, J. Angew. Chem., Int. Ed. Engl. 1980 19 563. 74. (a) Bu¨ hl, H.; Seitz, B.; Meier, H. Tetrahedron 1977 33 449. (b) Seybold, G.; Heibl, C. Chem. Ber. 1977 110 1225. 75. Scheithauer, S.; Mayer, R. Thioand Dithiocarboxylic Acids and Their Derivatives in Topics in Sulfur Chemistry ; Senning, A., Ed; Thieme: St uttgart, 1979; Vol. 4.(b) Lythgoe, B.; Waterhouse, I.; Tetrahedron Lett. 1977 18 4223. 76. Pederson, B. S.; Scheibye, S.; Clausen, K.; Lawesson, S.-O. Bull. Soc. Chim. Belg. 1978 87 293. 77. Katritzky, A.R.; He, H-Y.; Suzuki, K. J. Org. Chem. 2 000, 65, 8210.

PAGE 79

67 78. Katritzky, A.R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2 003, 68, 1443. 79. Katritzky, A.R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2 003, 68, 4932. 80. Katritzky, A.R.; Cai, C.; Suzuki, K.; Singh, S. K. J. Org. Chem. 2 004, 69, 811. 81. Katritzky, A.R.; Suzuki, K.; Singh, S. K.; He, H-Y. J. Org. Chem. 2 003, 68, 5720. 82. (a) Katritzky, A. R.; Moutou, J.-L.; Yang, Z. Synlett 1995 99. b) Katritzky, A. R.; Moutou, J.-L.; Yang, Z. Synthesis 1995 1497. 83. Walter, M.; Radke, M. Liebigs Ann. 1973 636. 84. Lbbecke S., Pfeil A., Krause H.H., Propellants, Explosives, Pyrotechnics 1999 24 168. 85. May W.P., Plastics Technology 1977 23(6) 97-105. 86. Tall A., Zeman S., J. Thermal Analysis 1977 12(1) 75. 87. Patil, A. J.; Muthusamy, E.; Mann, S. Angew. Chem. Int. Ed. 2004 43 4928. 88. Ullmann, F.; Gross, C. Ber. 1911 43 2694. 89. Greene, B.; McClure, M.B.; Johnson, H.T. Chem. H.&S 2004 11 6. 90. Johannes, D.; Turid, S. Act. Chem. Sc 1991 45(10) 1064. 91. Yoder, C.H.; Zuckerman, J.J. J. Am. Chem. Soc. 1966 88 4831. 92. Bates, H.A.; Condulis, N.; Stien, N.L. J. Org. Chem. 1986 51 2228. 93. (a) Maag, H.; Manukian, B. K. Helv. Chim. Acta 1973, 56 1787. (b) Blatt, A. H.; Bach, S.; Kresch, L. W. J. Org. Chem. 1957 22 1693. 94. Katritzky, A. R.; Scriven, E. F.V.; Majumder, S.; Akhmedova, R.G; Akhmedov, N. G.; Vakulenko A. V. ARKIVOC 2005 (iii) 179. 95. Rice, L.M.; Grogan, C.H.; Reid, E.E. J. Am. Chem. Soc. 1953 75 2261. 96. Gero A. J. Am. Chem. Soc. 1954 76 5158. 97. Thompson, D.M. U.S. Patent 6,013,143, 2000. 98. Braeunig, R.A. ( n.d. ). Rocket Propellants. Retrieved from http://www.braeunig.us/space/propel.htm Last accessed September 2005. 99. Rusek, J.; Palmer, K.B; Darren M. U.S. Patent 2,005,022,911, 2005.

PAGE 80

68 BIOGRAPHICAL SKETCH James William Rogers was born in Sandwhich, Illinois, on October 3rd, 1976, to William Edward Rogers and Barbara Jean Roge rs. Shortly after birth, the family moved to Aurora, Illinois, where they lived for four years. The family then moved to Phoenix, Arizona, for 2 years, and then moved back to the Midwest to Granite City, Illinois, which is close to St. Louis, Missouri. William Rogers supported the family by working as a chemist at Sigma-Aldrich. James Rogers graduated from Granite City Senior High School in 1995; he lettered varsity in foot ball but academic honors so far eluded him. James went to college at nearby Southern Il linois University at Edwardsville in the fall term of 1995. He paid all of his educati on expenses by working as a waiter at The Lawyers Club of St. Louis. Af ter receiving a Bachelor of Sc ience in chemistry at age 23, James began work at Abbott Labs in North Chic ago, Illinois, as a QC chemist. After four months the chemistry department at Southern Illinois called with an offer for admission to graduate school. He refused at first but after a week of thought decided to enroll and resigned his position at Abbott Labs. James enro lled in the graduate program at Southern Illinois in the summer of 2000, working under the tutelage of Professor Tim Patrick, whose novel research inspired James to conti nue his education. He received a Master of Science in chemistry in August of 2002, this time he graduated with high honors and received an award for outstanding chemical re search. James also met his future wife Hong Yu at Southern Illinois, who also receiv ed a Master of Science in chemistry in the summer of 2002. In the summer of 2002, H ong and James began their PhD study at the

PAGE 81

69 University of Florida and were married in 2003. James now works under the mentorship of Professor Alan Katritzky. On May 22nd, 2005, at 6 AM James and Hong were blessed by the birth of their daug hter, Elaine Yu Rogers.


Permanent Link: http://ufdc.ufl.edu/UFE0013389/00001

Material Information

Title: 1-Benzotriazolyl-2-Propynones as Novel 1,3-Biselectrophiles, Benzotriazole-Assisted Thioacylation and Synthesis of Energetic Materials
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: UFE0013389:00001

Permanent Link: http://ufdc.ufl.edu/UFE0013389/00001

Material Information

Title: 1-Benzotriazolyl-2-Propynones as Novel 1,3-Biselectrophiles, Benzotriazole-Assisted Thioacylation and Synthesis of Energetic Materials
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: UFE0013389:00001


This item has the following downloads:


Full Text












1-BENZOTRIAZOLYL-2-PROPYNONES AS NOVEL 1,3-BISELECTROPHILES,
BENZOTRIAZOLE-ASSISTED THIOACYLATION AND SYNTHESIS OF
ENERGETIC MATERIALS
















By

JAMES WILLIAM ROGERS


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


2006

































Copyright 2006

by

James William Rogers















ACKNOWLEDGMENTS

I would like to foremost thank my wife, Yu Hong, for her companionship and

guidance through my graduate career. There are many days that I might have failed in

my resolve to complete my goals if it were not for her love and ability to brighten my

spirits when it seemed there was no hope. I would also like to thank friends and some of

the co-workers I have met along my graduate career, who have helped me in my personal

life as well as my graduate life in chemistry: Dr. Rachel Witeck, Dr. Gary Cunningham,

Dr. Chia Pooput, Dr. Yi'an Zhai, and Hui Tao. I would also like to thank my parents,

William and Barbara Rogers, who always believed in and encouraged me to strive to be a

better man, as well as my sister, Jeannine Rogers, for her friendship. I would like to

thank all my other family members who gave me support and love throughout my life.

I am grateful for the help of Professor Alan Katritzky, whose great mind for novel

chemistry guided the research in these pages. I would also like to thank my mentors of

the past, most notably Professor Timothy Patrick, my research director at Southern

Illinois University, where I received a Master of Science in chemistry. His belief in my

abilities inspired me to continue my education at the University of Florida. There are

many teachers and instructors I would like to thank over the years, all of whom have

encouraged me and supported me to continue my stated goals.

I thank the Southern Illinois University at Edwardsville Chemistry Department for

both my undergraduate and first two years of graduate study. The staff prepared me well

for graduate school at the PhD level. Lastly, I thank the graduate department of the









University of Florida and the faculty of the Chemistry Department for accepting me,

especially Professor James Deyrup, into their graduate program and for expanding my

knowledge in chemistry greatly.
















TABLE OF CONTENTS



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

LIST OF TA BLE S ......... .... ........ .... .... ...... ....................... .... vii

LIST OF FIGURES .............................................. ........ ...... ............. viii

L IST O F SC H EM E S................... .................... .................... .. .. ............ .. .............. ix

ABSTRACT ........ .............. ............. ...... ...................... xi

CHAPTER

1 G EN ER A L IN TR O D U CTIO N ..................................................... .....................1

2 1-BENZOTRIAZOLYL-2-PROPYNONES AS NOVEL 1,3-
BISELECTROPHILIC SYNTHONS ............ ............................... ..................15

2 .1 Introdu action ................................................................................. 15
2.2 R results and D discussion ........................................ ......................... 17
2 .3 C o n clu sio n ................................................. ................ 2 1
2 .4 E x p erim mental ............... .... ................ ................ ............ .. .... ...........2 2
2.4.1 General Procedure for the Preparation of Substituted 1-
Benzotriazolyl-2-propynones 2.14a,b...................... ....................22
2.4.2 General Procedure for the Preparation of Pyrido[1,2-
a]pyrim idin-2-ones 2.17a-c ........................................................23
2.4.3 General Procedure for the Preparation of Quinolizin-2-ones
2 .19a- f ................... .....................................................24
2.4.4 General Procedure for the Preparation of Pyrido[1,2-a]quinolin-
3-ones 2.21a,b and 5-Phenylthiazolo[3,2-a]pyrimidin-7-one
(2.23).................................................................. 26

3 DEVELOPMENT OF BENZOTRIAZOLE ASSISTED THIOACYLATION
M E T H O D O L O G IE S ..................................................................... ..................28

3 .1 Introdu action ................................................................................. 2 8
3.2 R results and D discussion ........................................ ......................... 30
3 .3 C o n clu sio n ................................................. ................ 3 4
3.4 Experim ental Section ....................................................... .... ........... 34









3.4.1 General Pprocedure for the Preparation of 2-Amino-5-
nitrophenylam ides 3.10a-h ................................... ..................... 34
3.4.2 General Procedure for the Synthesis of Aliphatic and Aromatic
Thiocarbonyl-1H-6-nitrobenzotriazoles 3.11a-g ....................37
3.4.3 General Procedure for the Preparation of Thionoesters 3.12a-c...40

4 SYNTHESES AND CHARACTERIZATION OF ENERGETIC MATERIALS.42

4.1 Introduction ................ ... .. .. .........4........... .. 42
4.1.1 Synthesis and Characterization of Blowing Agents.....................42
4.1.2 Syntheses of Hypergolic Agents...... ........................................ 44
4.1.3 Synthesis of Dinitro-Substituted Five Membered Heterocycles....47
4.2 R results and D discussion .............................................................................47
4.2.1 Results Syntheses and Characterization of Blowing Agents.........47
4.2.2 Results Synthesis of Hypergolic Agents.....................................52
4.2.3 Results Nitration of Five Membered Heterocycles......................54
4 .3 C o n c lu sio n ........................................................................................... 5 5
4 .4 E xperim mental ............... ........................................ ........ ...... .... 55
4.4.1 General Procedure for the Preparation of
Benzo[1,2,3,4]thiatriazine-1,1-dioxides 4.5-4.6 ............................56
4.4.2 General Procedure for the Preparation of Pyrazolium Nitrate 4.8....57
4.4.2.1 General Procedure for the Preparation of Hypergolic
A m inals 4.9 and 4.10 ................................... .................. 57
4.4.2.2 General Procedure for the Preparation of Hypergolic
Agent Dimethyl(2-pyrrolidin-1-yl-ethyl)amine 4.11.........58
4.4.2.3 General Procedure for the Preparation of Hypergolic
Agent 1,3-(Dipyrrolidyl)propane 4.12............. ...............58
4.4.3 General Procedure for the Preparation of 2-Ethyl-3,5-
D initrothiophene 4.29 .................. ............. .. ..................... .... 59
4.4.4 General Procedure for the Preparation of 2,4-Dinitrothiophene
4.32, 2,5- Dinitrothiophene 3.33 .............. ............. ........ ....... 59

5 CON CLU SION ................................................. ....... ............. 60

L IST O F R E F E R E N C E S ...................................... .................................... ..................... ..... 62

BIO GRAPH ICAL SK ETCH .................................................. ............................... 68
















LIST OF TABLES

Table page

3-1 Preparation of thiocarbonylbenzotriazoles 3.6a-d.......... .......... ............... 31

3-2 Aliphatic and aromatic thiocarbonyl-1H-6-nitrobenzotriazoles 3.11a-g ................32

3-3 Thionoesters 3.12a-c ....................... .. .............. ......................... 34
















LIST OF FIGURES


Figure page

1-1 Electronic properties of benzotriazole ....................................... ........ ............... 2

1-2 M ethodologies for rem oval of benzotriazole. ........................................ .................3

1-3 G raebe-U lm ann reaction. ................................................ ............................... 4

1-4 Insertion of benzotriazole ........... ................. ............................. ............... 4

1-5 Transform nations w ith benzotriazole ........................................ ....................... 5

1-6 Cyclization mechanism for 1-benzotriazolyl-2-propynone.................... ........ 9

1-7 Blowing agents. ............................ ........ 13

1-8 Hypergolic fuels. .......................................... .. ...... ......... .... 13

2-1 Pyrido[1,2-a]pyrimidines possessing diverse biological activities .....................15

2-2 M echanism of cyclization reaction. .............................................. ............... 21

3-1 X-ray structure of bis(benzotriazolyl)-di-(4-methylphenylylthio)methane ............30

4-1 Blowing agents with reported melting points and DSCs. ......................................43

4-2 Energetic Additives without reported TGA analysis. ............................................44

4-3 Hypergolic fuels. .................................. ......... ......................46

4-4 TGA analysis of com pounds 4.5-4.7..................................... ........................ 50

4-5 X-ray of molecular complex of 4-nitropyrazole and oxalic acid 4.17 ...................51

4-6 TGA and DSC analysis of pyrazolium nitrate 4.8 ..............................................51
















LIST OF SCHEMES


Scheme p

1-1 N-Acylbenzotriazoles from acid chlorides. ...................................... ............... 6

1-2 N-Acylbenzotriazoles from sulfonylbenzotriazoles. ..............................................7

1-3 N-Acylbenzotriazoles from carboxylic acids and thionyl chloride........................7

1-4 N-,C- and S-Acylation of N-acylbenzotriazole. ........... .......... ....................... 8

1-5 Cyclization reactions of 1-benzotriazolyl-2-propynones. ......................................10

1-6 Synthesis of bis-(benzotriazolyl)methanethione 1.44 ............... .... ............. 10

1-7 Synthesis of unsymmetrical di- and trisubstituted thioureas 1.46......................... 11

1-8 Synthesis of thioacyl nitrobenzotriazoles 1.50.................................... ............... 11

1-9 Synthesis of thionoesters 1.52 ........... ..... ................................ 12

1-10 Synthesis of dinitrothiophenes. ................................................. 14

2-1 Literature methods for synthesis of pyrido[1,2-a]pyrimidin-2-ones......................16

2-2 2-Pyridylacetonitrile with 4-methyleneoxetan-2-one ...........................................17

2-3 Synthesis of substituted 1-benzotriazolyl-2-propynones. ........................................18

2-4 Reaction of 1-benzotriazol-1-yl-3-phenylpropynone and 2-aminopyridines..........18

2-5 Reaction of 2-picolines and 1-benzotriazolyl-2-propynones. ..............................19

2-6 Reaction of 2-methylquinoline and 1-benzotriazolyl-2-propynones. ....................20

2-7 Reaction of 2-aminothiazole and N-(phenylpropioyl)benzotriazole ......................20

2-8 Syntheis of pyrimido[2,1-b]benzothiazoles .................................................. .....20

2-9 Attempted synthesis of 2.23, 2.17a and 2.19a from 3-phenylpropiolic acid. .........21

3-1 Classical methods for the synthesis of thionoesters. .......................................28









3-2 Preparation of unsymmetrical di- and tri-substituted thioureas 3.3 ......................29

3-3 Preparation of thiocarbonylbenzotriazoles 3.6a-d. .............................. ............31

3-4 Preparation of thiocarbonyl-1H-6-nitrobenzotriazoles. .......................................32

3-5 Preparation of thionoesters .......... ................ ............................ .. ............. 33

4-1 Synthesis of 4.10 and 4.9. .............................................. .............................. 46

4-2 Synthesis of dimethyl-(2-pyrrolidin-l-yl-ethyl)amine 4.11................. ........ 47

4-3 Synthesis of 2-phenylbenzo[1,2,3,4]thiatriazine-1,1-dioxide 4.5. ............................48

4-4 Synthesis of com pound 4.6. .......................................................... .....................48

4-5 Synthesis of bis-benzo[1,2,3,4]thiatriazine-l,l-dioxide 4.7. ............................49

4-6 Synthesis of inter-chelating molecular complex of 4-nitropyrazole and oxalic
acid 4.17 ............................................................................50

4-7 Synthesis of cyclic aminal 4.10 from formaldehyde.................. .................52

4-8 Synthesis of cyclic aminal 4.9 from formaldehyde .................................................52

4-9 Synthesis of cyclic aminal 4.10 via reduction with LAH ........................................53

4-10 Synthesis of cyclic aminal 4.9 via reduction with LAH ........................................53

4-11 Synthesis of N,N-dimethyl-2-(1-pyrrolidinyl)-1-ethanamine 4.11 .......................53

4-12 Synthesis of 1,3-(dipyrrolidyl)propane 4.12. ................................................54

4-13 Synthesis of 2-ethyl-3,5-dinitrothiophene 4.29 ............... .................................. 54

4-14 Synthesis of mixture of 2,4- 4.32 and 2,5-dinitrothiophenes 4.33.........................55















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

1-BENZOTRIAZOLYL-2-PROPYNONES AS NOVEL 1,3-BISELECTROPHILES,
BENZOTRIAZOLE-ASSISTED THIOACYLATION AND SYNTHESIS OF
ENERGETIC MATERIALS

By

James William Rogers

May 2006

Chair: Alan R. Katritzky
Major Department: Chemistry

New synthetic strategies for the synthesis of several target molecules are the theme

of this work. 1-Benzotriazolyl-2-propynones were shown to be novel 1,3-bis-electrophilic

synthons. These synthons provided a new route in the synthesis of pyrido[1,2a]pyrimidin

-2-ones, 2H-quinolizin-2-ones, pyrido[1,2-a]quinolin-3-ones, and thiazolo[3,2-a]-

pyrimidin-7-ones. These new 1,3-bis-electrophilic synthons were compared with previous

1,3-bis-electrophilic methodologies from the literature and expanded on the role of these

synthons by novel synthesis of new heterocyclic systems.

Aliphatic and aromatic thiocarbonyl-1H-6-nitrobenzotriazoles were synthesized

(Chapter 3) as novel thioacylating reagents. To show their synthetic utility, these

thiocarbonyl-1H-6-nitrobenzotriazoles were reacted with an alcohol to form the

corresponding thionoesters.









Chapter 4 summarizes the work accomplished in collaboration with the US Army

on the reasonable synthesis and characterization of broadly defined energetic materials.














CHAPTER 1
GENERAL INTRODUCTION

Syntheses of heterocyclic compounds possessing synthetic utility, biological

activity and desirable physical properties are a constant area of interest for organic

chemists, medicinal chemists and material scientists. Efficient methodologies for the

synthesis of target molecules through the use of convenient starting materials, mild

conditions and less laborious isolation and purification are highly sought after. This

dissertation provides novel synthetic routes to fused heterocycles, thionoesters and

energetic materials.

Versatile synthetic methodologies employing benzotriazole as a leaving group are

covered in the first two chapters of this dissertation. Over the previous two decades,

benzotriazole (Bt) has been used in countless synthetic processes including multistep

preparations of drugs, preparation of biologically active compounds and synthetic

analogs of natural products.1 This is due to the multifaceted nature of benzotriazole and

its unique electronic properties that enable it to act as an electron-donating or electron-

withdrawing moiety, depending on the functional group attached to the benzotriazole

nitrogen. Indeed, many applications of benzotriazole depend upon its leaving ability 1.1,

its ability to enhance a-proton acidity 1.2, and its electron donor properties 1.3 (Figure 1-

1). Generally, benzotriazole is considered to be comparable with cyano and

phenylsulfonyl groups as a leaving group 1.1 or as an activator of a-CH proton loss 1.2.1

Benzotriazole also possesses electron donating characteristics 1.3 when there is an a-

heteroatom on the carbon attached to nitrogen.











;N "N N,
N+
RX RX
1.1 1.2 1.3
good leaving activates CH electron donor
group to proton loss properties



-N N 'N
"N %N N N
1.4 \\ N+ X-
H 14 1.5 1 .6
RC'=X+ RX R H
R ^R
Figure 1-1. Electronic properties of benzotriazole.

Benzotriazole is an inexpensive and stable compound that is highly soluble in

ethanol, benzene, toluene, chloroform, DMF and is slightly soluble in water.2 It is also

very soluble in basic solutions because of the acidity of the nitrogen hydrogen (pKa of

8.2).3 Benzotriazole is considered to be a useful synthetic auxiliary because it displays

three important properties: i) it is readily removed at the end of a synthetic sequence

(benzotriazole is especially advantageous because it can be recovered at the end of the

reaction and reused), ii) it is easily introduced at the beginning of a reaction, and iii)

lastly it is stable to various reaction conditions and can possibly activate other groups on

the molecule.

Benzotriazole has been proven in hundreds of publications to be a good leaving

group and can be efficiently removed at the end of a synthetic sequence by i) nucleophilic

substitution 1.11 4a-e ii) elimination 1.12 5a-e iii) hydrolysis 1.10 6a-e and iv) ring scission7

(Figure 1-2).










Nu- Nu
N X
[ N [ N 1. Removal by H-Y
Si N' Nucleophilic Substitution
1.8 1.11
R X R 1.8
H Y
R
1.7 H 1.9- X
-H+ Y
2. Removal by elimination 1.12
H20

R
4. Removal by =O 3. Removal by Hydrolysis
Ring Scission HY
1.10
Figure 1-2. Methodologies for removal of benzotriazole.

The first three modes of removal all involve initial dissociation of benzotriazole

into its anion 1.8 and formation of cation 1.9. Dissociation is assisted by a suitable

hetero-atom X and by a proton or Lewis acid catalyst which facilitates the departure of

benzotriazole. The leaving ability of benzotriazole is also heavily influenced by the

presence of other functional groups exemplified by group Y; for instance to remove

benzotriazole by elimination, group Y must be connected to a hydrogen (Figure 1-2).

Removal of benzotriazole by ring scission is different from the first three examples in

that benzotriazole does not remain intact; instead its ring structure is cleaved. Probably

the most well known example of ring scission on benzotriazole is the Graebe-Ulmann

reaction in which carbazole 1.16 is formed from loss of N2 from 1-phenylbenzotriazole

1.137 (Figure 1-3). The reaction is thought to form a diradical intermediate 1.14a or an

iminocarbene intermediate 1.14b which then undergoes cyclization to form (R)-4bH-

carbazole 1.15 which isomerizes via hydrogen shift to carbazole 1.16.












N N -N2 N
Ph
1.13 1.14a 1.14b


H
N

/\ /


N


1.16 1.15
Figure 1-3. Graebe-Ulmann reaction.

A good synthetic auxiliary should be able to be inserted into the molecule of

interest quite readily, and indeed benzotriazole has been successfully inserted in many

diverse systems. Benzotriazole derivatives can be obtained through displacement of a

halogen in i) alkyl,8 or ii) acyl halides9, iii) though displacement of hydroxyl groups in

alcohols,10 and by displacement of alkoxy groups in iv) acetals11 or ketals.12

Benzotriazole can also be inserted by addition to v) aldehydes13 (including conjugate

analogues), vi) imines,14 vii) iminium salts,15 and enamines16 (Figure 1-4).

By Addition

By Substitution 5. C=00 B Bt :1 -'; N
/ / Bt .


1. RX + Bt -- R-Bt
2. RCOX + Bt--- RCOBt \ / BtH HN-
3. ROH + -B- 6. C=N Bt
R-Bt/ Bt

4. OR + Bt- R Bt 7. \ +/ Bt- N-
R OR R OR C=N Bt
Figure 1-4. Insertion of benzotriazole.

As stated earlier in the introduction a useful synthetic auxiliary should be stable to

various reaction conditions and possibly activate other groups on the molecule. There are

several transformations from the literature in which benzotriazole does not leave and is










retained after the reaction. The most important of these transformations are i)

deprotonation,17 ii) substitution, 8iii) addition,19iv) isomerization between 1- and 2-

substituted benzotriazoles,20v) isomerization of benzotriazole within the molecule,21 and

vi) proton loss followed by rearrangement22 (Figure 1-5).

1. Proton loss followed by reaction with electrophile

Bt -H+ Bt E+ Bt
H /E
X X X
X=unactivated, C=C or hetero(aroamtic), heteroatom

2. Substitution either alpha to Bt-group or otherwise
Bt Nu- Bt
OC -C-- /
/ X / 'Nu

X=halogen or OR
3. Addition of Bt-C-X to C=C-Y

S NR2(or OR) NR2
C=C\ -C-C-Bt
Bt-C-X X-C I

4. Isomerization of Bt1 and Bt2

N N N -R


5. Isomerization of Bt group within molecule

C-C=C C=C-C
Bt Bt

6. Proton loss followed by rearrangement H
Bt-C-C=C -- Bt-C-C=C Bt-C=C-C
H
Figure 1-5. Transformations with benzotriazole.

Due to the unique electronic properties of benzotriazole the Katritzky group has

developed numerous synthetic methodologies employing it as a synthetic auxiliary in the

synthesis of countless heterocycles as well as other organic molecules. These reactions









are typically shorter, offer higher conversion to product, and avoid the use of unstable or

toxic chemical reagents such as acid chlorides.1

Over the last couple of years the Katritzky group has focused much of its attention

on N-acylbenzotriazoles. Studies on N-acylazoles as acylating agents are nothing new;

they have been studied since the 1960's by the Staab group.23 N-Acylazoles have been

typically synthesized from the corresponding acid chlorides 1.16 and N-

acylbenzotriazoles 1.18 can also be synthesized in this manner23 (Scheme 1-1).

O O
RjC + Bt-H R- K Bt
R1 Ci R1 Bt
1.16 1.17 1.18
Scheme 1-1. N-Acylbenzotriazoles from acid chlorides.

Although the synthesis of N-acylazoles is routine, the requirement of their synthesis

from acid chlorides is problematic and they can be both physiologically dangerous as

well as unstable. Recently the Katritzky group discovered two new methodologies for

the synthesis of N-acylbenzotriazoles that do not require the use of acid chlorides. The

first methodology uses a sulfonylbenzotriazole as a counter attack reagent.24 25a When a

carboxylic acid 1.19 is exposed to a suitable base such as Et3N the hydroxy group is

deprotonated froming a carboxylate that can then undergo nucleophilic substitution with

the electrophilic sulfonylbenzotriazole forming a mixed carboxylic sulfonic anhydride

1.20. Benzotriazole anion 1.21 is then thought to counterattack the mixed carboxylic

sulfonic anhydride intermediate 1.20 to form the corresponding N-acylbenzotriazole 1.18

(Scheme 1-2).









O BtSO2R2 O O 0
OH Et3N O-S-R + Bt- + Et3NH+ R1
11 EBt

1.19 1.20 O 1.21 1.22 1.18
Scheme 1-2. N-Acylbenzotriazoles from sulfonylbenzotriazoles.

The Katritzky group later found that N-acylbenzotriazoles 1.18 could be

synthesized by simply treating the carboxylic acid 1.19 in the presence of thionyl chloride

and excess benzotriazole 1.1726 (Scheme 1-3). This methodology is often more

advantageous than synthesizing N-acylbenzotriazoles from the previous route (Scheme 1-

2) since thionyl chloride and benzotriazole are commercially available while sulfonyl-

benzotriazole has to be prepared in a separate step.

0 1.19
O O R10
SO1 II II 0
2.5 BtH C2 S and/or A1 sOH O
BtBt Bt --- Bt RI"
Bt
1.17 1.23 1.24 1.18
Scheme 1-3. N-Acylbenzotriazoles from carboxylic acids and thionyl chloride.

A wide range of N-acylbenzotriazoles have been synthesized through these two

different methodologies, including alkyl, aryl, heterocyclic, unsaturated, and other

functionally substituted derivatives.24'26 There are several acid chlorides with the same

functionalities as the synthesized N-acylbenzotriazoles that are unstable, difficult to

prepare or in some cases unknown.27

Reactions with N-acylbenzotriazoles have been extensively studied by the

Katritzky group over the past 5 years. N-Acylbenzotriazoles have been found to undergo

N-,C- and S-acylation with the following reagents: i) amines (ammonia, primary and

secondary) to form amides,25a ii) thiols to form thiol esters,28 iii) heterocycles under

Friedel-Crafts reaction conditions to form C-acylated heterocycles,29 C-acylated with iv)

(a) ketones,25e (b) cyanides30 and (c) sulfones31 to form B-diketones, 3-ketonitriles and 3-










ketosulfones respectfully, v) ethyl acetoacetate to form p-ketoesters and vi) a-

acetylketones to form complex P-diketones32 (Scheme 1-4).

Ri=Alkyl, Aryl
O Het- furan, thiophene,
H Rpyroles, indoles
Het R1
3. R1=Aromatics, 1.27 O
Heteroaromatics R
R2=Ph, Bn, Et, R2S R1 2 1.28
COCH3, CH2CO2H 0 3 0
1.26 R R1
R2 R1,R2 =H, Me,aryl
S 0 R3 =Me,aryl


R, O -1. NH3, NH2R2, NHR2R3
R3 R1 NEt3
1.25
R1=Alkyl, Aryl 0,
R2,R3=H, Alkyl, Aryl


O O
II II


R2 R
R3 CN
1.29

R1,R2 =H, Me,aryl
R3 =Me,aryl


R2


R1 R2 O R3
1.32 0 0 R1
R1, R2=Alkyl, Aryl, heteroaryl Ri ^A OEt 1.30
1.31 R1,R2 =H, Me,aryl
R3 =Me,aryl
Ri=Alkyl, Aryl, heteroaryl
Scheme 1-4. N-,C- and S-Acylation of N-acylbenzotriazole.

N-Acylbenzotriazoles have been successfully acylated using a variety of

nucleophiles and the yields have been comparable to other methods which mainly used

acid chlorides as the acylating reagent.27 N-Acylbenzotriazoles offer advantages over the

corresponding acid chlorides in their stability towards hydrolysis, their chemo-selectivity

and crystallinity. It should be noted that they are especially advantageous when acid

chlorides are unknown, difficult to prepare, handle and/or store. For these reasons the

Katritzky group has expanded the research on N-acylbenzotriazoles and created










numerous examples of derivatives that have been successfully acylated with several types

of nucleophiles.

In Chapter 2 1-benzotriazolyl-2-propynones are shown to be very interesting N-

acylbenzotriazoles because they behave as 1,3-bis-electrophiles. 1-Benzotriazolyl-2-

propynones undergo cyclization with 1,3-bis-nucleophiles to form various a-unsaturated

cyclic ketones through the following mechanism (Figure 1-6).

H+

R R
H -H+ HX X+ R RcH O
HX~XH Bt X Bt
X=CH, NH HX



0- R
0 -_Bt- r Bt X X pO -H+ R
X X X X -BHX X

Bt
Figure 1-6. Cyclization mechanism for l-benzotriazolyl-2-propynone.

1-Benzotriazolyl-2-propynones 1.33 (Chapter 2) were reacted with 2-amino-

pyridines 1.35, 2-picolines 1.34, 2-methylquinoline 1.37 and 2-aminothiazole 1.36 to

form pyrido[1,2-a]pyrimidin-2-ones 1.39, 2H-quinolizin-2-ones 1.38, pyrido[1,2-

a]quinolin-3-ones 1.41, and thiazolo[3,2-a]pyrimidin-7-ones 1.40 in moderate to

excellent yields (Scheme 1-5).

Successful applications of N-acylbenzotriazoles as novel acylating reagents have

also prompted investigation into a second area of study (chapter 3): the use of bis-

(benzotriazolyl)methanethione as a mild thioacylating reagent.33 Bis-(benzotriazolyl)-

methanethione 1.44 is easily prepared from 1-trimethylsilylbenzotriazole 1.43 and

thiophosgene 1.42 in quantitative yield34 (Scheme 1-6).











1.34
1.38 Rz 1 3- 5 R1 1.39
R1 "" N NH2
N R1 R AN. N N

RNO Bt R__ O
(39- 81%) 1.36 1.33 1.37 (71- 78%)
S NH2 N H3
C /-



S 1.40 1.41

QN 0 N
N ON N
Ph R O
(53%) (40%)
Scheme 1-5. Cyclization reactions of 1-benzotriazolyl-2-propynones.

S S
CI.,, + Bt-TMS Bt Bt
1.42 1.43 1.44
Scheme 1-6. Synthesis of bis-(benzotriazolyl)methanethione 1.44.

There was only one example from the literature before 2003 in which bis-

(benzotriazolyl)-methanethione was reacted with an amine (aniline) to form a thiourea

(diphenyl-thiourea).34 The Katritzky group greatly expanded the work for the preparation

of unsymmetrical di- and trisubstituted thioureas using compound 1.44 as a thiophosgene

equivalent. First bis-(benzotriazolyl)methanethione 1.44 was reacted with one equivalent

of a primary amine to form 1-(alkyl/arylthiocarbamoyl)-benzotriazoles 1.45 in near

quantitative yields (Scheme 1-7). Then compound 1.45 was further reacted with either a

primary or secondary amine to form unsymmetrical di- and trisubstituted thioureas 1.46.









R1
S H_ S R1NH R1 S
R-NH2 S R2.N N
Bt Bt Bt NR R2 HN-R
1.44 1.45 H 1.46
Scheme 1-7. Synthesis of unsymmetrical di- and trisubstituted thioureas 1.46.

It was found by Katritzky et al. that the thiocarbamoylbenzotriazoles 1.45

synthesized were stable at room temperature for several weeks. Thiocarbamoyl-

benzotriazoles 1.45 are masked isothiocyanates and are superior to them because they are

more stable and their reactions with amines are faster, higher-yielding and less laborious

in isolation and purification.33

Chapter 3 of this dissertation expands upon the previous work on thiocarbamoyl-

benzotriazoles 1.45 by preparing a broad range of reagents for thioacylation, namely

thioacyl nitrobenzotriazoles 1.50.35 A previous route established by the Rapoport group

was used to synthesize aliphatic, aromatic and heterocyclic substituted derivatives.36ab

Treatment of 4-nitrobenzene-1,2-diamine 1.47 with the corresponding acid

chlorides 1.48 gave regioselectively the intermediate amides 1.49, which were then

converted to the corresponding thioamides by phosphoruspentasulfide and then cyclized

by treatment with sodium nitrate in acetic acid to yield the corresponding thioacyl

nitrobenzotriazoles 1.50 (Scheme 1-8).

^ NHH2 NNH
INH2 ROCI 1) P2S5\ IN
IROI NH2 25 2NL R=alkyl, aryl,
O2N N NH2 1.48 02N NH 2)HONO heteroaryl
1.47 1.49 O 1.50 S' R
0 0

Scheme 1-8. Synthesis of thioacyl nitrobenzotriazoles 1.50.

It was found that all thioacyl nitrobenzotriazoles 1.50 were stable at room

temperature for several weeks and they readily reacted with 1-naphthalenol 1.51 to

produce thionoesters 1.52 in good to almost quantitative yield (Scheme 1-9).











N NEt3
N' N R '^ J!
1.50 S R 1.51 1.52
R=alkyl, aryl, heteroaryl
Scheme 1-9. Synthesis of thionoesters 1.52

As part of a collaborative project with the US Army on development of energetic

materials (Chapter 4), synthesis of three different types of energetic materials was

accomplished (blowing agents, hypergolic agents and dinitrosubstituted five membered

heterocycles).

Blowing agents are very well known as explosive formulations but they are not

only limited to this role; for instance, dinitropentamethylenetetramine (DNPT) andp-

tolylsulfonylhydrazine (PTS) are employed in the production of microcellular rubber.37

Some blowing agents such as azodicarbonamide (ADCA) are used in the plastics industry

to provide polymer films.38-40 Blowing agents are also useful additives in propellant

formulations.41-43

The US Army employs trinitrotoluene (TNT) and cyclotrimethylenetrinitramine

(RDX) formulations as explosives. Blowing agents included in these formulations ideally

should display separate isotherms from the other components of the explosive mixture.

Addition of these blowing agents in explosive formulations provides a means to temper

the cook off violence of the explosion. The following compounds were synthesized as

potential blowing agent candidates from methodologies which could be easily scaled-up

(Figure 1-7). The evaluation of the thermal properties of these compounds is included in

chapter 4.










"N N
N
S
0S N02
02

1.53 1.54


CNH -0
N H +NH -O
02 1i 1
1.55 NN 1.56
Figure 1-7. Blowing agents.

Hypergolic agents are compounds that can be used as fuels and oxidizers which

ignite on contact with one another and therefore do not need a source of ignition.44

Hypergolic propellants have advantages over other propellants such as cryogenics

in that they are easily stored and are relatively inert until they are in contact with the

other agent. Since hypergolic propellants do not need an ignition source, they are often

the propellant of choice for spacecraft and satellites as they are required to stop and start

their engines thousands of times over the design life of the vehicle, thereby eliminating

one source of possible failure.45 Synthesis of the following hypergolic fuels was

requested by the US Army that could potentially be scaled-up to provide 50-100 g

quantities (Figure 1-8).

Me Me
I I
N N CMe

Ne N. Me N Me
Me
1.57 1.58 1.59 1.60
Figure 1-8. Hypergolic fuels.

Dinitro derivatives of five-membered heterocycles may be of interest as energetic

materials and/or possible blowing agent candidates. They have also been shown to have

diverse biological activity; for instance 2,4-dinitroimidazole derivatives have been shown









to be very effective agents in increasing the sensitivity of hypoxic cells toward irradiation

in cancer radiotherapy.46 Numerous dinitro heterocycles have also been shown to be

useful intermediates; for instance Padwa and Watterson recently converted dinitro furan

into various polysubstituted phenols through SnAr nucleophilic substitution reactions.47

Two dinitro heterocyclic derivatives 1.62, 1.64, 1.65 (dinitrothiophenes isolated as a

mixture of isomers) were successfully synthesized in moderate to excellent yield with

more examples planned for future work (Scheme 1-10).

02N
/0\ HNO3,TFAA /
r S S NO2
1.61 1.62
NO2 NO2
N02 NH4NO3 N02 +

STFA,TFAA 02N 02N N2
1.63 1.64 ratio 1.5:1 1.65
Scheme 1-10. Synthesis of dinitrothiophenes.

In summary, an efficient synthesis of three types of energetic materials was

developed. The previously unreported decomposition profiles for three blowing agent

candidates were analyzed by thermal analysis for evaluation as possible munitions

additives. The fourth blowing agent candidate's 1.56 decomposition profile was

analyzed by TGA and DSC. Also, several novel fused heterocyclic derivatives were

synthesized by reacting 1,3-bisnucleophiles with 1-benzotriazolyl-2-propynones. Finally,

thioacyl nitrobenzotriazoles were shown to be effective thioacylating reagents and are a

viable alternative to previous problematic routes.
















CHAPTER 2
1-BENZOTRIAZOLYL-2-PROPYNONES AS NOVEL 1,3-BISELECTROPHILIC
SYNTHONS

2.1 Introduction

As a structural motif pyrido[ 1,2-a]pyrimidines have shown very diverse biological

activities,48 for this reason these compounds have become interesting synthetic targets

over the previous years. Their structural motif can be seen below in the tranquilizer

pirenperone,49a the antiallergic agent ramastine,49 an antiulcerative agent,49 and an

antiasthmatic agent49d (Figure 2-1).








raenn Ramastine Antiallergic Agent
N CHO
O NO
0 N OC2 F NILI N
0





astine Antia llergsthmatic Agent
-i N
0 N N N
N OC2H5 0 N-N(O K0
0 0
TBX Antiasthmatic Agent
Antiulcerative
Figure 2-1. Pyrido[1,2-a]pyrimidines possessing diverse biological activities.

All the examples from Figure 1 are pyrido[1,2-a]pyrimidin-4-ones which are the

most studied class due to their biological activity. Due to the interests these compounds

have generated numerous synthetic routes are available for their synthesis.50 In

comparison, pyrido[1,2-a]pyrimidin-2-ones are a less studied class although there are









several literature methods that were found (Scheme 1-1) for their synthesis: i) cyclization

of 2-aminopyridine 2.1 with ethyl cyanoacetate 2.2 at 80-100 C and 14 kbar;51 ii) the

cyclization of 2-aminopyridine with the Vilsmeier-Haack 2.3 reagent prepared in situ

from N-alkyl-N-arylethoxycarbonylacetamide and phosphorus oxychloride, which always

affords a mixture of the pyrido[1,2-a]pyrimidin-2-ones and pyrido[1,2-a]pyrimidin-4-

ones;52 iii) reaction of phenylpropiolic ester 2.4 with 2-aminopyridine, which forms a

significant amount of undesired side products;53'48 (iv) reaction of dimethyl hex-2-en-4-

yne-1,6-dioate 2.554 or allene-l,3-dicarboxylic esters 2.655 with 2-aminopyridines; and v)

acid catalyzed cyclization of N-acetoacetylated 2-amino pyridines/picolines/quinolines

2.7 under microwave assisted synthesis.56

0 CI
+ H3CO Ph + Ph C
N NH2 R NH Ph CO2Et
2.3 1 N NH2
2.1 2.3 2.1 2.4
(ii)
S(iii)

H CH 1 CN (i) (iva) + Me02CM
N NH2 2H50 N NH COMe
2.1 2.2 R- O 2.1 2.5
2.1 2.5

(i) R = NH2 CO2Me
|I j1 0 0 o (ii)R=N(R1)P h N + IH
N v CH3 o(ii) R = N(R)Ph NH
N H (iii) R Ph N21 CO2Me
2.7 CO2Me
(iva) R = -/ 2.6
(ivb) R = CH2CO2Me
(v) R = CH3
Scheme 2-1. Literature methods for synthesis of pyrido[ 1,2-a]pyrimidin-2-ones.

Surprisingly compared to pyrido [1,2-a]pyrimidin-2-ones quinolizin-2-ones are of a

sparsely studied class of compounds; there is only one reported synthetic procedure. Only

one quinolizin-2-one derivative was found from the literature, 4-methyl-2-oxo-2H-

quinolizine-1-carbonitrile 2.10 which is formed by the reaction of 2-pyridylacetonitrile









2.8 with 4-methyleneoxetan-2-one 2.9 (Scheme 2-2).57 There were no reported examples

from the literature that used picolines in the place of 2-aminopyridines in the reaction

with acetylenic carboxylic acid derivatives to form the corresponding quinolizin-2-ones.


CN
N N + Me
2.8 2.9 2.10
Scheme 2-2. 2-Pyridylacetonitrile with 4-methyleneoxetan-2-one.

There are numerous examples in the literature which employ N-acylbenzotriazoles

as mild and neutral N-acylating agents. Some examples include the preparation of

primary, secondary, and tertiary amides25a including formylation25b and

trifluoroacylation.25c N-Acylbenzotriazoles are used for regioselective C-acylation of

ketone enolates into a-diketones25e and are also used for the O-acylation of aldehydes.25d

The Katritzky group has an efficient method for the synthesis of N-acylbenzotriazoles

from acetylenic-carboxylic acids.26 1-Benzotriazolyl-2-propynones are formed from the

reaction of acetylenic-carboxylic acids and thionyl chloride and benzotriazole. These

compounds are 1,3-bis-electrophiles and their reaction with 2-aminopyridines leads to an

improved syntheses of pyrido[1,2-a]pyrimidin-2-ones.

2.2 Results and Discussion

Two examples of alkyl and aryl substituted 1-benzotriazolyl-2-propynones were

synthesized, 1-benzotriazol-l-yl-3-phenylpropynone and 1-benzotriazol-l-yl-oct-2-yn-1-

one 2.14a,b which were prepared in 87% and 95% yield (Scheme 2-3). 1-Benzotriazol-1-

yl-3-phenylpropynone 2.14a was previously reported by our group26; 1-benzotriazol-l-yl-

oct-2-yn-l-one 2.14b is a novel compound.










0 0
R O + 2.5SOC12 + 3BtH R -
OH Bt
2.11 2.12 2.13 2.14a: R = Ph (87%)
2.14b: R = C5H (95 %)
Scheme 2-3. Synthesis of substituted 1-benzotriazolyl-2-propynones.

The first attempted synthesis of pyrido[1,2-a]pyrimidine-2-one 2.17a (conducted at

80-100 C in acetonitrile for 2-4h in a sealed tube), found that a significant amount of

byproduct 2.16 was obtained along with the desired product 2.17a. In order to isolate the

byproduct 1-benzotriazol-l-yl-3-phenylpropynone, compound 2.14a and 2-amino-

pyridine 2.15a were reacted at a lower temperature 80 C with refluxing and in less time

(2 hr), compound 2.17a was isolated in 27% yield along with the by-product 2.16 in 46%

yield (Scheme 2-4). The by-product 2.16 is probably formed by the counter attack of

benzotriazole anion with 1-benzotriazol-l-yl-3-phenylpropynone 2.14a. It was found that

byproduct 2.16 formation was significantly decreased by conducting the reaction under

harsher conditions using a sealed tube at 120 C for 12 hours allowing clean conversion

to the pyridopyrimidine 2.17a (R = Ph) in 71 % yield after column purification (Scheme

2-4). Use of 4- and 5-methyl substituted 2-aminopyridines also resulted in the formation

of corresponding pyridopyrimidines 2.17b and 2.17c in yields of 73% and 71%.


S0 MeCN Bt Bt
S+ Ph -- + N
N NH2 2.14a Bt 122.16 Ph

2.15a: R=H 2.17a: R=H (71%)
2.15b: R=5-methyl 2.17b: R=8-methyl (73%)
2.15c: R=4-methyl 2.17c: R=7-methyl (71%)
Scheme 2-4. Reaction of 1-benzotriazol-1-yl-3-phenylpropynone and 2-aminopyridines.

Synthesis of 2H-quinolizin-2-ones was performed by reacting 2-picoline with 1-

benzotriazol-l-yl-3-phenylpropynone 2.14a in a sealed tube at 120 C in acetonitrile for

12 hours. This afforded the expected quinolizin-2-one 2.19a in 61% yield (Scheme 2-5).









Similarly, reactions of 1-benzotriazol-1-yl-3-phenylpropynone 2.14a and 1-benzotriazol-

1-yl-oct-2-yn-1-one 2.14b with 2-picoline derivatives afforded the corresponding 2H-

quinolizin-2-ones 2.19b-f in moderate to good yields.

RI
R1
R 0 MeCN R2
R2 + R--N
N Bt 1200C
R 0
2.18 2.14a,b 2.19
Scheme 2-5. Reaction of 2-picolines and l-benzotriazolyl-2-propynones.

2.19 R R1 R2 Yield (%)
a Ph H H 61
b Ph H CN 81
c Ph H Ph 50
d Ph H Me 51
e C5H11 H H 39
f Ph 9-methyl H 53

Surprisingly few reports were found in the literature on reactions of propionates

and 2-picoline or its derivatives leading to the formation of fused ring systems. The

reaction of 2-methylpyridine-l-oxide with methyl-3-phenyl-2-propanoate to give methyl-

2-(2-methyl-3-pyridyl)-3-oxo-3-phenyl)propanoate is the only known analogue.58 1-

Benzotriazolyl-2-propynones 2.14a,b react easily as 1,3-bis-electrophilic synthons to

give fused ring products, since they are very good acylating reagents.

The N-acylbenzotriazole methodology, developed for the preparation of pyrido[1,2-

a]pyrimidin-2-ones and 2H-quinolizin-2-ones, has also been extended to provide access

to the fused ring systems of pyrido[1,2-a]quinolin-3-ones and thiazolo[3,2-a]pyrimidin-7-

ones. Reactions of 2-methylquinoline 2.20 with 1-benzotriazol-l-yl-3-phenylpropynone

2.14a or 1-benzotriazol-l-yl-oct-2-yn-l-one 2.14b in a sealed tube at 120 C in









acetonitrile afforded the expected 1-phenyl- and 1-pentylpyrido[1,2-a]quinolin-3-ones

2.21a,b in 40% yields (Scheme 2-6).

0 MeCN
N R N 'Bt
R
N CH3 Bt 1200C
2.20 2.14 a,b R 0
2.21a: R=Ph (40 %)
2.21b: R=C5H11 (40 %)
Scheme 2-6. Reaction of 2-methylquinoline and 1-benzotriazolyl-2-propynones.

Reaction of 2-aminothiazole 2.22 with 1-benzotriazol-1-yl-3-phenylpropynone

2.14a in a sealed tube at 120 C in acetonitrile afforded the expected 5-phenylthiazolo

[3,2-a]pyrimidin-7-one 2.23 in 54% yield (Scheme 2-7).

0S
SNH2 Ph0 B MeCN C N O
N Bt 1200C -
2.22 2.14a 2.23 h 54 % yield
Scheme 2-7. Reaction of 2-aminothiazole and N-(phenylpropioyl)benzotriazole.

Synthesis of analogous pyrimido[2,1-b]benzothiazoles 2.26 from acetylenic acids

2.25 and 2-aminobenzothiazoles 2.24 has been previously reported (Scheme 2-8).59

i R1 S
RI I />NH2 + R3-- CO2H 1-butanal N O
R2 -N R2 0
2.24 2.25 2.26 R3
Scheme 2-8. Syntheis of pyrimido[2, 1-b]benzothiazoles.

Application of this procedure to the synthesis of pyrido[ 1,2-a]pyrimidin-2-one

2.17a, 2H-quinolizin-2-one 2.19a and thiazolo[3,2-a]pyrimidin-7-one 2.23 did not

provide the desired products in the cases of pyrido[1,2-a]pyrimidin-2-one 2.17a and

thiazolo[3,2-a]pyrimidin-7-ones 2.23. For 2H-quinolizin-2-one 2.19a, only trace amounts

of product were isolated from a complex reaction mixture after 2 days (Scheme 2-9).









S

I >-NH2 + Ph-- CO2H t N

2.22 2.27 Ph 2.23


rN + Ph CO2H N NN
N NH2
2.15a 2.27 Ph
2.17a

+C 1-butanal
+ Ph CO2H N
N CH3
2.18a 2.27 h 2.19a
Scheme 2-9. Attempted synthesis of 2.23, 2.17a and 2.19a from 3-phenylpropiolic acid.

The following reaction mechanism is proposed for either pyrido[1,2-a]pyrimidin-2-

ones 2.17 or 2H-quinolizin-2-one 2.19 although the other fused ring systems would be

analogous. First conjugate addition of the pyridine nitrogen to the 1-benzotriazolyl-2-

propynone forming in allenoic intermediate, followed by cyclocondensation, gave the

corresponding fused heterocyclic ring (Figure 2-2).


| + R H
N X Bt N XHn-1
RC'-CC-c'O-
Bt




N ^Xn.2 .BfH N XHn~1 i'N
RA -0 t R-0 R --COBt
Bt
Figure 2-2. Mechanism of cyclization reaction.

2.3 Conclusion

In comparison, our N-acylbenzotriazole methodology offers shorter reaction times,

cleaner conversion to products, and higher yields then the literature procedures to









synthesize pyrido[1,2-a]pyrimidin-2-ones. 1-Benzotriazolyl-2-propynones were also

shown to be useful synthons for the synthesis of new heterocyclic systems.

2.4 Experimental

Melting points were determined using a Bristoline hot-stage microscope and are

uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a 300

MHz NMR spectrometer in chloroform-d solution. Elemental and mass spectroscopy

analyses were performed by Analytical Laboratories, Dept. of Chem., University of

Florida. THF was distilled from sodium-benzophenone ketyl prior to use. All the

reactions were performed in flame dried glassware and column chromatography was

performed on silica gel (200-425 mesh).

2.4.1 General Procedure for the Preparation of Substituted 1-Benzotriazolyl-2-
propynones 2.14a,b

To a solution ofbenzotriazole (2.96 g, 24.8 mmol) and thionyl chloride (5.55 mL,

20.8 mmol) in methylene chloride (20 mL), the appropriate acid (8.3 mmol) was added.

The reaction mixture was stirred at room temperature for 3h. Solvent was removed under

vacuum and the resultant solid was re-dissolved in ethyl acetate. The organic layer was

washed with water, IN NaOH (200 mL x 2), and brine. Recrystallization from ethyl

acetate afforded the desired 1-benzotriazolyl-2-propynones in 80-95% yields.

1-Benzotriazol-l-yl-3-phenylpropynone (2.14a). White microcrystals (87%), mp

119-123 oC. 1H NMR 6 7.31 -7.63 (m, 4H), 7.73 7.78 (m, 1H), 7.84 7.87 (m, 2H),

8.22 (d, J= 8.1 Hz), 1H), 8.37 (d, J= 8.1 Hz, 1H). 13C NMR 6 81.5, 94.8, 114.1, 118.2,

120.5, 127.2, 129.5, 130.6, 131.3, 132.4, 133.4, 145.9, 149.8. Anal. Calcd for C15H9N30:

C, 72.86; H, 3.67; N, 16.99. Found: C, 72.55; H, 3.56; N, 16.98.









1-Benzotriazol-l-yl-oct-2-yn-l-one (2.14b). Yellow oil (95%). 1H NMR 6 0.93 -

0.98 (m, 3H), 1.36 1.54 (m, 4H), 1.73 1.78 (m, 2H), 2.61(t, J = 7.2 Hz, 2H), 7.53 (t, J

= 7.8 Hz, 1H), 7.68 (t, J= 7.8 Hz, 1H), 8.15 (d, J= 7.8 Hz, 1H), 8.27 (d, J= 8.1 Hz, 1H).

13CNMR 6 13.9, 19.4, 22.1, 27.1,31.0, 100.4, 114.2, 120.3, 126.3, 126.5, 130.5, 130.9,

146.2, 150.2.

2.4.2 General Procedure for the Preparation of Pyrido[1,2-a]pyrimidin-2-ones
2.17a-c.

1-Benzotriazol-1-yl-3-phenylpropynone (200 mg, 0.90 mmol) and substituted 2-

aminopyridine (0.90 mmol) were added to acetonitrile (3 mL) in a sealed tube and heated

to 120 C with stirring for 12 hours. Solvent was removed under vacuum and the crude

mixture was separated by silica column chromatography (30% ethyl acetate/hexanes to

remove benzotriazole, then 5% methanol/chloroform to elute product). Recrystallization

from ethyl acetate afforded the desired pyrido[1,2-a]pyrimidin-2-ones in 71-88% yields.

4-Phenyl-2H-pyrido[1,2-a]pyrimidin-2-one (2.17a). Yellow microcrystals (71%),

mp 226-228 C (Lit. mp 227-228 oC).6 1H NMR 6 6.51 (s, 1H), 6.69 6.74 (m, 1H),

7.32 7.39 (m, 1H), 7.45 7.47 (m, 2H), 7.52 7.55 (m, 1H), 7.58 7.61 (m, 3H), 7.72

(d, J= 7.2 Hz, 1H). 13C NMR 6 112.6, 117.1, 125.3, 128.8, 129.6, 129.7, 130.8, 135.7,

148.6, 152.5, 168.1. Anal. Calcd For C14H10N20: C, 75.66; H, 4.54; N, 12.60. Found: C,

74.90; H, 4.39; N, 12.54.

8-Methyl-4-phenylpyrido[1,2-a]pyrimidin-2-one (2.17b). Orange microcrystals

(73%), mp 210-211 oC. H NMR 6 2.15 (s, 3H), 6.45 (s, 1H), 7.27 7.32 (m, 1H), 7.38 -

7.45 (m, 4H), 7.56- 7.60 (m, 3H).13C NMR 6 18.0, 117.1, 122.7, 124.9, 126.9, 128.9,

129.7, 130.8, 131.1, 138.9, 148.5, 151.6, 168.3. Anal. Calcd For C15H12N20: C, 76.25; H,

5.12; N, 11.86. Found: C, 75.20; H, 5.01; N, 12.08.









7-Methyl-4-phenylpyrido[1,2-a]pyrimidin-2-one (2.17c). Red microcrystals

(71%), mp 160-162 oC. 1HNMR 6 2.36 (s, 3H), 6.43 (s, 1H), 6.53 (d, 1H, J= 7.4 Hz),

7.13 (s, 1H), 7.40 7.43 (m, 2H), 7.56 7.61 (m, 4H). 13C NMR 6 21.3, 115.5, 116.8,

123.1, 128.9, 129.0, 129.6, 130.8, 131.0, 147.9, 148.4, 152.6, 168.4. Anal. Calcd For

C15H12N20: C, 76.25; H, 5.12; N, 11.86. Found: C, 75.77; H, 5.36; N, 11.40.

2.4.3 General Procedure for the Preparation of Quinolizin-2-ones 2.19a-f.

1-Benzotriazol-1-yl-3-phenylpropynone or 1-benzotriazol-1 -yl-oct-2-yn-1-one

(0.90 mmol) and the appropriate 2-picoline derivative (0.90 mmol) were added to

acetonitrile (3 mL) in a sealed tube and heated to 120 oC with stirring for 12 hours.

Solvent was removed under vacuum and the crude mixture was separated by silica

column chromatography (30% ethyl acetate/hexanes to remove benzotriazole, then 5%

methanol/chloroform to elute product). Recrystallization from ethyl acetate afforded the

substituted quinolizin-2-ones in 50-81 % yields.

4-Phenylquinolizin-2-one (2.19a). Amber microcrystals (61%), mp 189-191 oC.

H NMR 6 6.49 6.54 (m, 1H), 6.74 (d, J= 2.7 Hz, 1H), 6.85 (d, J= 2.7 Hz, 1H), 7.11 -

7.16 (m, 1H), 7.26 7.34 (m, 1H), 7.37 7.54 (m, 3H), 7.59 7.61 (m, 2H), 7.71 (d, J=

7.5 Hz, 1H). 13CNMR6 111.5, 112.4, 124.4, 124.8, 128.4, 128.7, 129.1, 129.4, 129.6,

130.3, 132.9, 145.0, 146.0, 175.4. HRMS (El) Found [M] 221.0852; C15H11NO requires

221.0841.

2-Oxo-4-phenyl-2H-quinolizin-l-carbonitrile (2.19b). Amber microcrystals

(81%), mp 170-172 oC. H NMR 6 6.76 6.82 (m, 2H), 7.30 (s, 1H), 7.46 7.49 (m,

2H), 7.55 7.58 (m, 1H), 7.62 7.65 (m, 3H), 7.82 7.91 (m, 2H). "3C NMR 6 94.9,

113.8, 115.5, 122.5, 125.2, 129.0, 129.2, 129.9, 130.9, 131.3, 131.7, 133.5, 147.05, 148.4.









Anal. Calcd For C16H10N20: C, 78.03; H, 4.09; N, 11.38. Found: C, 71.82; H, 3.96; N,

11.97.

1,4-Diphenylquinolizin-2-one (2.19c). Amber microcrystals (50%), mp 223-225

oC. 1H NMR 6 6.43 (ddd, J= 7.2, 6.3, 1.2 Hz, 1H), 6.93 (s, 1H), 6.95 (ddd, J= 7.5, 6.3,

1.2 Hz, 1H), 7.22 (d, J= 9.3 Hz, 1H), 7.40 7.44 (m, 3H), 7.50 7.56 (m, 4H), 7.60 -

7.63 (m, 3H), 7.73 (d, J= 7.2 Hz, 1H). 3C NMR 6 111.4, 123.3, 123.8, 124.4, 127.6,

127.9, 128.8, 129.2, 129.5, 129.7, 130.1, 131.0, 133.5, 134.8, 142.6, 145.1, 173.7. Anal.

Calcd For C21H15NO: C, 84.82; H, 5.08; N, 4.71. Found: C, 84.29; H, 5.01; N, 4.66.

1-Methyl-4-phenylquinolizin-2-one (2.19d). Dark purple oil (51%). 1H NMR 6

2.36 (s, 3H), 6.41 (t, J= 6.3 Hz, 1H), 6.80 (s, 1H), 7.07 7.12 (m, 1H), 7.39 7.42 (m,

2H), 7.44 (d, J= 4.8 Hz, 1H), 7.48 7.55 (m, 3H), 7.68 (d, J= 7.5 Hz, 1H). 13C NMR 6

10.3, 111.0, 118.1, 122.0, 122.4, 127.7, 129.1, 129.4, 129.9, 130.0, 133.5, 141.6, 144.3,

174.4. Anal. Calcd for C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C, 66.53; H, 4.85;

N, 5.48.

4-Pentylquinolizin-2-one (2.19e). Dark purple oil (39%). 1H NMR 6 0.95 (m, 3H),

1.37 -1.46 (m, 4H), 1.73 (t, J= 7.5 Hz, 2H), 2.83 (t, J=7.9 Hz, 2H), 6.54 (d, J= 4.2 Hz,

1H), 6.63-6.68 (m, 1H), 6.75 (d, J= 2.7 Hz, 1H), 7.06 7.11 (m, 1H), 7.16 7.19 (m,

1H), 7.82 (d, J= 7.5 Hz, 1H). 13C NMR 6 13.9, 22.3, 26.2, 31.3, 32.4, 111.2, 112.6,

122.7, 125.3, 127.2, 128.0, 145.0, 145.2, 175.8. HRMS (EI) Found [M] 215.1300;

C14H17NO requires 215.1310.

9-Methyl-4-phenylquinolizin-2-one (2.19f). Red microcrystals (53%), mp 206-

208 oC. H NMR 6 2.40 (s, 3H), 6.42 (t, J= 7.2 Hz, 3H), 6.79 (s, 2H), 7.00 (d, J= 6.6 Hz,

1H), 7.42 7.45 (m, 2H), 7.57 -7.62 (m, 4H). 13C NMR 6 19.6, 109.0, 111.4, 124.1,









127.9, 128.0, 129.1, 129.5, 130.1, 131.0, 133.6, 145.3, 146.5, 175.8. Anal. Calcd for

C16H13NO: C, 81.68; H, 5.80; N, 5.95. Found: C, 68.25; H, 5.57; N, 5.56.

2.4.4 General Procedure for the Preparation of Pyrido[1,2-a]quinolin-3-ones
2.21a,b and 5-Phenylthiazolo[3,2-a]pyrimidin-7-one (2.23).

1-Benzotriazol-1-yl-3-phenylpropynone or 1-benzotriazol-1 -yl-oct-2-yn-1-one

(0.90 mmol) and the appropriate substituted 2-methylquinoline or 2-aminothiazole (0.90

mmol) were added to acetonitrile (3 mL) in a sealed tube and heated to 120 C with

stirring for 12 hours. Solvent was removed under vacuum and the crude mixture was

separated by silica column chromatography (30% ethyl acetate/hexanes to remove

benzotriazole, then 5% methanol/chloroform to elute product). Recrystallization from

ethyl acetate afforded the pyrido[1,2-a]quinolin-3-ones in 40 % yield and 5-

phenylthiazolo[3,2-a]pyrimidin-7-one in 54% yield.

1-Phenylpyrido[1,2-a]quinolin-3-one (2.21a). Dark purple oil (40%). 1H NMR 6

6.57 (d, J= 3 Hz, 1H), 6.79 (d, J= 3 Hz, 1H), 6.95 7.08 (m, 3H) 7.22 7.27 (m, 1H),

7.31 -7.36 (m, 3H), 7.38- 7.45 (m, 3H), 7.52- 7.55 (m, 1H). 13C NMR 6 114.3, 123.1,

124.0, 125.4, 125.6, 125.8, 127.4, 127.6, 128.2, 129.3, 129.4, 130.0, 135.3, 137.3, 145.7,

148.6, 177.7. Anal. Calcd For C19H13NO: C, 84.11; H, 4.83; N, 5.16. Found: C, 84.82; H,

4.72; N, 5.11.

1-Pentylpyrido[1,2-a]quinolin-3-one (2.21b). Dark purple oil (40%). 1H NMR 6

0.81 (t, J= 6.9 Hz, 3H), 1.17 1.22 (m, 4H), 1.61 (t, J= 7.2 Hz, 2H), 3.05 (t, J= 7.8 Hz,

2H), 6.47 (d, J= 2.4 Hz, 1H), 6.77 (d, J= 2.4 Hz, 1H), 6.95 (d, J= 9.0 Hz, 1H), 7.24 -

7.28 (m, 2H), 7.49 7.59 (m, 2H). 13C NMR 6 13.8, 22.2, 29.9, 31.1, 34.9, 113.5, 121.4,

123.5, 124.4, 125.9, 126.0, 127.9, 128.3, 219.2, 134.8, 145.3, 151.2, 177.7. Anal. Calcd

For CisH19NO: C, 81.47; H, 7.22; N, 5.28. Found: C, 80.47; H, 7.33; N, 5.25.






27


5-Phenylthiazolo[3,2-a]pyrimidin-7-one (2.23). White plates (54%), mp 161-164

C (Lit. mp 191-194 C).15 1H NMR 6 6.15 (s, 1H), 7.22 (d, J= 4.2 Hz, 1H), 7.35 (d, J=

4.8 Hz, 1H), 7.59 7.65 (m, 5H). 13C NMR 6 98.2, 109.8, 110.8, 123.3, 128.6, 129.2,

130.7, 131.2, 147.9, 166.5. Anal. Calcd For C12HsN20S: C, 63.14; H, 3.53; N, 12.27.

Found : C, 60.14; H, 3.48; N, 12.07. *Note while the mp was considerably lower then

what the literature reported the author feels that since the product was isolated as an

amorphous solid the mp would be lower than uniform crystals.
















CHAPTER 3
DEVELOPMENT OF BENZOTRIAZOLE ASSISTED THIOACYLATION
METHODOLOGIES

3.1 Introduction

Thionoesters (R-C(S)-OR) have been a focus of interest due to their different

reactivities relative to their oxygen analogues.60,61 For example they can be desulfanated

using Raney nickel to form ethers. 62 This is a good path to convert esters to ethers while

avoiding problems associated with steric and functional limitations.63 Thionoesters have

been shown to react with DAST under mild conditions to form a,a-difluoroethers, which

are compounds of current interest.64 1,3,4-Oxadiazoles65 can also be synthesized using

thionoesters as starting material, these compounds have generated considerable interests

due to their use as plant cell growth hormones, herbicides, and fungicides.66'67

Thionoesters have recently been found to be effective chain transfer agents in various

polymerizations including styrene, methyl acrylate and other related olefins.68

Several examples of various methodologies for the synthesis of thionoesters are

depicted on Scheme 3-1 below.

R20 0OR2
I BF4-
R
(ii) Na2S, CH3CN
(i) T
NH H2S, Pyridine (iii) S
R, O-R2 RI -O-R2 HOR2 R1,i X

(iv)
(V) P4S10 HOR2
Xylene Reflux

R
Scheme 3-1. Classical methods for the synthesis of thionoesters.
Scheme 3-1. Classical methods for the synthesis of thionoesters.









Example (i) is sulfur-hydrolysis of iminoesters with hydrogen sulfide in pyridine.

Unfortunately thioamides are often a major side product and the methodology was

limited in scope69,70. Example (ii)is sulfo-hydrolysis of dialkoxycarbonium ions, which

often results in mixtures requiring lengthy purification techniques.71'72 Examples (iii) and

(iv) are alcoholysis of thioacyl halides73 and thioketenes74 to thionoesters. Thioacyl

halides are generally very unstable, only thiobenzoyl chlorides see much use. Aliphatic

thioacyl halides decompose even at -70 C.75 Thioketenes have a similar problem to

thioacyl halides in that they are also very unstable and dimerize rapidly unless kept at a

very low temperature. Direct thionation of an ester with phosphorus sulfide reagents to

give the corresponding thionoester is shown in example (v) on Scheme 2.1.76 This is

probably the best procedure for synthesizing thionoesters but the reaction conditions are

long and harsh refluxingg xylene or toluene), and is limited to compounds which do not

have sensitive functional groups.

The Katritzky group has applied N-acylbenzotriazoles to the syntheses of amides,77

0-keto sulfones,78 a-substituted P-ketonitriles,79 oxazolines and thiazolines,80 and C-

acylated-pyrroles and -indoles.81 The Katritzky group recently reported the application of

thioacylating reagent, bis(benzotriazolyl)methanethione 3.1, in the preparation of

unsymmetrical di- and tri-substituted thioureas 3.3 by intermediate 1-

(alkyl/arylthiocarbamoyl) benzotriazoles 3.233 (Scheme 3-2).

RZ
S NH S
R-NH R R R R
A Bt N'R RN N' Bt= N
Bt Bt H R2 H N

3.1 3.2 3.3
Scheme 3-2. Preparation of unsymmetrical di- and tri-substituted thioureas 3.3









This work has been greatly extended by preparing a range of reagents for

thioacylation (RCSBt), thiocarbamoylation (RR'NCSBt), aryl/alkoxythioacylation

(ROCSBt), and aryl/alkylthiothioacylation (RSCSBt). This report will detail the work

completed on reagents for thioacylation, namely thioacyl nitrobenzotriazoles. Reactions

of thioacyl nitrobenzotriazoles with oxygen nucleophiles gave the corresponding

thionoesters in good yield.

3.2 Results and Discussion

It should be noted that Rachel M. Witek of the Katritzky group found that the direct

reaction of bis(benzotriazolyl)methanethione 3.1 with Grignard reagents provides low

yields (12-34%) of bis(benzotriazolyl)diarylsulfidemethanes (Figure 3-1) instead of

thiocarbonylbenzotriazoles. Due to these unsatisfactory results alternate routes to

thiocarbonylbenzotriazoles were investigated.




N /N
: N/

--

O:N -N
C27H22N6S2
Exact Mass: 494.13
Mol. Wt.: 494.64
C, 65.56; H, 4.48; N, 16.99; S, 12.97
Figure 3-1. X-ray structure of bis(benzotriazolyl)-di-(4-methylphenylylthio)methane.

In previously reported syntheses of thioamides in one-pot reactions from Grignard

reagents, carbon disulfide, and amines mediated by 1-trifluoromethyl-

sulfonylbenzotriazole;82ab the putative intermediate thiocarbonyl benzotriazoles 3.6 were

evidently formed, but were not isolated. Decomposition of analogous methyl-substituted

thioacylimidazoles has been reported.83 1-Chlorobenzotriazole is used (instead of 1-









trifluoromethylsulfonyl-benzotriazole) as the mediating reagent which allows isolation of

3.6 in some cases (Scheme 3-3).

Rachel M. Witek prepared thiocarbonylbenzotriazoles 3.6a-d from carbon

disulfide, 1-chlorobenzotriazole and the respective Grignard or organolithium reagents

(Table 3.1). The benzenoid thiocarbonylbenzotriazoles (63-89%) are all stable reddish

solids. Benzotriazol-l-yl-4-methylphenyl methanethione 3.6a displays the characteristic

1H NMR shifts for benzotriazole overlapping with aromatic shifts of the p-tolyl group

67.39 (d, J= 8.4 Hz, 2H), 7.55 (t, J= 7.5 Hz, 1H), 7.71 (t, J= 7.5 Hz, 1H), 8.14-8.19 (m,

3H), 8.39 (d, J= 8.4 Hz, 1H)}. A 13C NMR shift -170 ppm is common for the

thiocarbonyl in compounds 3.6a-d.


R-MgBr S2 2 BtC1 R1R2 R N"R1
THF R SMgBr R Bt R
3.4 3.5 3.6 3.7
Scheme 3-3. Preparation of thiocarbonylbenzotriazoles 3.6a-d.

Table 3-1. Preparation of thiocarbonylbenzotriazoles 3.6a-d.
3.6 R % Yield
a 4-Tolyl 63
b 4-Methoxyphenyl 89
c Phenyl 76
d 4-Chlorophenyl 42

One limitation of this method is that it is restricted to Grignard compatible

functionalities. In addition, while benzenoid aryl Grignard reagents react quite smoothly

to give thiocarbonylbenzotriazoles 3.6, only poor yields are attained for alkyl, alkynyl,

and heteroaryl Grignard reagents. In Rachel's hands, attempts to obtain n-butyl

substituted thiocarbonylbenzotriazole in higher yield by conducting the reactions at 0 C

and at -78 C failed. Likewise conversion ofn-butyllithium to n-butylzinc bromide or n-









butylcuprous bromide for reactions with carbon disulfide and 1-chlorobenzotriazole also

failed.

The stability of non-benzenoid thiocarbonylbenzotriazoles thus appears to be poor.

Rapoport utilized the route of Scheme 3-4 to obtain aliphatic thiocarbonyl-1H-6-

nitrobenzotriazoles in good yields (48-67%). 36a,b Apparently, the electron-withdrawing

nitro group on the benzotriazole moiety improves the stability and allows the isolation of

aliphatic thiocarbonylbenzotriazoles 3.11. Following this methodology, several novel

aliphatic and aromatic thiocarbonyl-1H-6-nitrobenzotriazoles 3.11b-g were prepared

(compound 3.11a was previously synthesized by Rapoport) (Scheme 3-4, Table 3-2).

SNH2 NH2 N
SRCOCI 1) p2S5
7 NH N N
02N NH, 3.9 02N R 2) HONO 02N
O S
3.8 3.10 3.11
Scheme 3-4. Preparation of thiocarbonyl-1H-6-nitrobenzotriazoles.

Table 3-2. Aliphatic and aromatic thiocarbonyl-1H-6-nitrobenzotriazoles 3.11a-g.
3.11 Acid Chloride 3.9 Amide 3.10 Thiocarbonyl-6-nitrobenzotriazole 3.11
R = (% yield) (% yield from 3.10)
a Ethyl 84 52
b 4-Methylphenyl 98 80
c 2-Furanyl 95 80
d 4-Nitrophenyl 83 69
e 4-Methoxyphenyl 86 66
f 4-Bromophenyl 99 45
g Pentyl 81 53
h 2-Thienyl 91 81

Treatment of 4-nitrobenzene-1,2-diamine 3.8 with the respective acid chlorides 3.9

gave regioselectively the intermediate amides 3.10 (83-99%). Resonance and the

inductive effect of the nitro group lowers the nucleophilicity of the amino group in the

para position, leaving the meta amino group to attack the carbonyl of the acid chloride









3.9. Amides 3.10 were converted to thioamides in crude yields of 59-96% by stirring at

room temperature with phosphorus pentasulfide (Scheme 2-3, Table 2-2). Thioamides

were cyclized by treatment with sodium nitrite and acetic acid to afford thiocarbonyl-1H-

6-nitrobenzotriazoles 3.11a-g in 45-80% yields from the corresponding amides 3.10.

Thiocarbonyl-6-nitro-1H-benzotriazoles 3.11a-g are all stable reddish solids. (6-

Nitrobenzotriazole- -yl)propane-1-thione 3.11a shows the characteristic H NMR {8.31

(d, J= 8.9 Hz, 1H), 8.44 (dd, J= 8.9, 1.8 Hz, 1H), 9.74 (s, 1H)} and 13C NMR

shiftsll3.1, 121.2, 121.7, 131.7, 149.0, 149.4), which correspond to 6-nitro-1H-

benzotriazole. The thiocarbonyl 13C NMR shift of thiocarbonyl-6-nitro-1H-benzotriazoles

3.11 is further downfield compared to thiocarbonylbenzotriazoles 3.6 and is found at

211.6 ppm for 3.11a. Although this method is general and alkyl derivatives are obtained

in moderate overall yields (44-72%), from 4-nitrobenzene-1,2-diamine 3.8 and the

respective acid chlorides 3.9, the lengthy 3-step procedure is a drawback. Thus, the

Grignard method of Scheme 2 is the preferred means of obtaining arylthiocarbonyl-

benzotriazoles while Rapoport's synthesis is preferred for alkyl, alkynyl, and heteroaryl

thiocarbonylbenzotriazoles.

Thiocarbonyl-6-nitrobenzotriazoles 3.11 e,d,h were reacted with 1-naphthol

providing thionoesters 3.12a-c in 62-99% yields (Scheme 3-5, Table 3-3).

S
R S OH
\ 0R
N N NO2 +

NN

3.11 d,e,h 3.12 a-c
Scheme 3-5. Preparation of thionoesters.









Table 3-3 Thionoesters 3.12a-c
Thionoesters 3.12 Alcohol Thioacylating Agent Yield (%)
R=
a 1-Naphthyl 4-Methoxyphenyl (3.10e) 88
b 1-Naphthyl 4-Nitrophenyl (3.10d) 99
c 1-Naphthyl 2-Thienyl (3.10h) 62

3.3 Conclusion

Application of benzotriazole reagents for aryl/alkoxythioacylation (ROCSBt) to the

syntheses of several novel thionoesters has been successfully developed. Advantages of

benzotriazole methods are primarily that use of unstable or hazardous reagents is

avoided, the mild conditions employed are tolerable of a large variety of functional

groups, and yields are comparable and in many cases higher than previously reported

methods.

3.4 Experimental Section

Melting points were determined using a Bristoline hot-stage microscope and are

uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a 300

MHz NMR spectrometer in chloroform-d solution. Elemental and mass spectroscopy

analyses were performed by Analytical Laboratories, Dept. of Chem., University of

Florida. THF was distilled from sodium-benzophenone ketyl prior to use. All the

reactions were performed under a nitrogen atmosphere and in flame dried glasswares.

Column chromatography was performed on silica gel (200-425 mesh).

3.4.1 General Pprocedure for the Preparation of 2-Amino-5-nitrophenylamides
3.10a-h.

Et3N (3.0 g, 30 mmol) was added to a solution of 4-nitrobenzene-1,2-diamine

(3.06 g, 20 mmol) in THF (100 mL) at -40 oC, followed by dropwise addition of the

respective acid chloride (20 mmol). The mixture was stirred at -40 C for 3h and at rt

overnight. The precipitate was filtered off and the filtrate evaporated to dryness in vacuo.









The residue was recrystallized from EtOH to afford the desired 2-amino-5-

nitrophenylamides 3.10a-h in 81-99 % yields.

N-(2-Amino-5-nitrophenyl)propionamide (3.10a). Yellow microcrystals (84 %),

mp 189-191 C, (Lit.23 mp 191 oC). H NMR 6 1.10 (t, J= 7.6 Hz, 3H), 2.38 (q, J= 7.6

Hz, 2H), 6.49 (s, 2H), 6.76 (d, J= 9.0 Hz, 1H), 7.84 (dd, J= 9.0, 2.5 Hz, 1H), 8.27 (d, J=

2.5 Hz, 1H), 9.13 (s, 1H). 13C NMR 6 9.6, 28.9, 113.6, 121.2, 121.7, 122.6, 135.5, 148.9,

172.6.

N-(2-Amino-5-nitrophenyl)-4-methylbenzamide (3.10b). Yellow needles (98%),

mp 197-198C. 0 H NMR 6 2.39 (s, 3H). 6.59 (s, 2H), 6.82 (d, J= 9.1 Hz, 1H), 7.34 (d, J

= 8.1 Hz, 2H), 7.91 (d, J= 9.2 Hz, 1H), 7.93 (d, J= 8.1 Hz, 2H), 8.15 (d, J= 2.6 Hz, 1H),

9.68 (s, 1H). 13C NMR 6 21.0, 113.9, 121.4, 123.5, 128.0, 128.8, 131.4, 135.4, 141.6,

150.6, 165.9. Anal. Calcd. For C14H13N303: C, 61.99; H, 4.83; N, 15.49. Found: C, 62.35;

H, 4.76; N, 15.13.

N-(2-Amino-5-nitrophenyl)furan-2-carboxamide (3.10c). Yellow needles (95

%), mp 176-1780C. 1HNMR 6 6.61 (s, 2H), 6.71 (dd, J= 3.3, 1.5 Hz, 1H), 6.81 (d, J=

9.0 Hz, 1H), 7.33 (d, J= 3.6 Hz, 1H), 7.91-7.94 (m, 2H), 8.06 (d, J= 2.4 Hz, 1H), 9.69

(s, 1H). 13C NMR 6 112.1, 113.9, 114.9, 120.4, 123.8, 135.4, 145.6, 147.4, 150.9, 157.0,

168.0. Anal. Calcd. For CllH9N304: C, 53.44; H, 3.67; N, 17.00. Found: C, 54.65; H,

3.28; N, 13.25.

N-(2-Amino-5-nitrophenyl)-4-nitrobenzylamide (3.10d). Brown needles (83%),

mp 303-305 oC. H NMR 6 6.58 (s, 2H), 6.84 (d, J= 9 Hz, 1H), 7.93 (dd, J= 9, 2.4 Hz,

1H), 8.25-8.30 (m, 4H), 8.38 (s, 1H). 13C NMR 6113.6, 122.8, 123.1, 123.8, 129.3,









129.6, 129.7, 148.0, 148.4, 150.8, 193.5. Anal. Calcd. For C13H10N405: C, 51.66; H, 3.33.

Found: C, 52.03; H, 3.39.

N-(2-Amino-5-nitrophenyl)-4-methoxybenzylamide (3.10e). Brown needles

(86%), mp 221-224 oC. 1HNMR 6 3.84 (s, 3H), 6.59 (s, 2H), 6.80 (d, J= 9.3 Hz, 1H),

7.08 (d, J= 9.3 Hz, 2H), 7.91 (dd, J= 9.3, 2.7 Hz, 1H), 8.00 (d, J= 2.7 Hz, 1H), 8.11 (d,

J= 2.4 Hz, 1H), 9.62 (s, 1H). 13C NMR 6 55.6, 113.6, 114.0, 121.7, 123.7, 130.1, 130.8,

135.5, 150.9, 162.1, 165.6, 204.5. Anal. Calcd. For C14H13N303: C, 58.53; H, 4.56; N,

14.63. Found: C, 58.55; H, 4.57; N, 14.09.

N-(2-Amino-5-nitrophenyl)-4-bromobenzylamide (3.10f). Brown needles (99%),

mp 222-223 oC. 1H NMR 6 6.65 (s, 2H), 6.80 (d, J= 9 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H),

7.91-7.98 (m, 3H), 8.11 (s, 1H), 9.83 (s, 1H). 13C NMR 6 114.0, 121.1, 124.0, 125.6,

130.3, 131.4, 133.5, 135.4, 151.0, 161.8, 165.4. Anal. Calcd. For C13H10NBrO2: C, 46.45;

H, 3.00; N, 12.50. Found: C, 46.34; H, 2.93; N, 11.89.

N-(2-Amino-5-nitrophenyl)hexylamide (3.10g). Brown needles (81%), mp 130-

131 oC. H NMR 6 0.90 (t, J= 6.6 Hz, 3H), 1.32-1.34 (m, 4H), 1.62 (quintet, J= 6.6 Hz,

2H), 2.37 (t, J= 6.6 Hz, 2H), 6.49 (s, 2H), 6.78 (d, J= 9 Hz, 1H), 7.85 (dd, J= 9.0, 2.4

Hz, 1H), 8.31 (d, J= 2.4 Hz, 1H), 9.16 (s, 1H). 13C NMR 6 14.0, 22.1, 24.9, 31.1, 36.0,

113.8, 121.2, 121.9, 122.7, 135.7, 148.8, 172.1. Anal. Calcd. For C12H17N303: C, 57.36;

H, 6.82; N, 16.72. Found: C, 57.88; H, 7.04; N, 15.97.

N-(2-Amino-5-nitrophenyl)thiophene-2-carboxamide (3.10h). Brown needles

(91%), mp 192-196 oC. H NMR 6 6.65 (s, 2H), 6.81 (d, J= 9 Hz, 1H), 7.22-7.25 (m,

1H), 7.86-7.95 (m, 2H), 8.03-8.09 (m, 2H), 9.81 (s, 1H). 13C NMR 6 114.0, 120.8,









124.0, 128.2, 129.9, 131.9, 135.5, 139.5, 151.1, 160.8, 167.6. Anal. Calcd. For

CliH9N303S: C, 50.18; H, 3.45; N, 15.96. Found: C, 49.98; H, 3.29; N, 15.43.

3.4.2 General Procedure for the Synthesis of Aliphatic and Aromatic
Thiocarbonyl- 1H-6-nitrobenzotriazoles 3.11a-g.

Phosphorus pentasulfide (2.22g, 10 mmol) was mixed with Na2CO3 (0.54 g, 5

mmol) in dry THF (150 mL). The mixture was stirred at rt for lh and then cooled to 0 oC.

The amide 9 (10 mmol) was added in one portion and the resulting mixture stirred at 0 C

for 3 hrs and rt for 10 hrs. The mixture was filtered and the filtrate evaporated to dryness,

the residue was dissolved in EtOAc (100 mL) and washed with 5 % NaHCO3 (2 x 30

mL), and the aqueous layers back-extracted with EtOAc (100 mL). The combined

organic layers were washed with brine, dried with MgSO4 and evaporated to obtain a

residue. The residue was placed on a silica-gel column and eluted with hexanes/ EtOAc

(5:1) to give thioamides in crude yields of 59-96 %.

Sodium nitrite (0.21 g, 3 mmol) was added to a stirred solution of the obtained

thioamide (2 mmol) dissolved by gentle warming in aqueous acetic acid 95 % (25 mL)

and then cooled to 0 C. The resulting mixture was stirred at 0 C for 45 min., then ice-

cold water (100 mL) was added and the precipitated product was filtered and washed

with water. Compound 3.11g was an exception requiring sonication and extraction with

EtOAc, which entailed washing the aqueous solution three times with 50 mL EtOAc,

collection of the organic layers and washing them with water (2 x 30mL) and brine (40

mL), drying with sodium sulfate, and filtration. The obtained solid was dried in vacuo

overnight to afford the desired thiocarbonyl-1H-6-nitrobenzotriazoles 3.11a-h in 45-81

% yields from the amides 3.10a-h.









(6-Nitrobenzotriazol-l-yl)propane-l-thione (3.11a). Orange microcrystals (52

%),mp 107-109 C, (Lit.23 mp 108 C). H NMR 6 1.54 (t, J= 7.1 Hz, 3H), 3.79 (q, J=

7.1 Hz, 2H), 8.31 (d, J= 9.0 Hz, 1H), 8.44 (dd, J= 9.0, 1.8 Hz, 1H), 9.74 (s, 1H). 13C

NMR 13.4, 40.6, 113.1, 121.2, 121.7, 131.7, 149.0, 149.4, 211.6.

(4-Methylphenyl)-(6-nitrobenzotriazol-l-yl)methanethione (3.11b). Red

microcrystals (80 %), mp 140-141 oC. 1H NMR 6 2.45 (s, 3H), 7.29 (d, J= 8.0 Hz, 2H),

7.72 (d, J= 8.0 Hz, 2H), 8.32 (d, J= 9.0 Hz, 1H), 8.44 (dd, J= 9.0, 1.1 Hz, 1H), 9.42 (s,

1H). 13C NMR 621.8, 112.1, 121.2, 121.5, 129.1, 131.2, 133.1, 139.4, 145.1, 148.8,

148.9, 200.5. Anal. Calcd. For C14H10N402S: C, 56.37; H, 3.38; N, 18.78. Found: C,

56.65; H, 3.29; N, 18.69.

Furan-2-yl-(6-nitrobenzotriazol-l-yl)-methanethione (3.11c). Orange

microcrystals (80%), mp 162 oC. 1HNMR 6 6.79 (dd, J= 3 Hz, 1.5 Hz, 1H), 7.66 (d, J=

3.6 Hz, 1H), 8.00 (d, J= 0.9 Hz, 1H), 8.32 (d, J= 9 Hz, 1H), 8.43 (dd, J= 9 Hz, 2.1 Hz,

1 H), 9.47 (d, J= 1.8 Hz, 1H). 13C NMR 6 112.1, 114.4, 121.2, 121.4, 122.4, 132.9,

148.6, 148.8, 151.8, 154.3, 180.1. Anal. Calcd. For CllH6N403S: C, 48.17; H, 2.21.

Found C, 47.83; H, 2.12.

(4-Nitrophenyl)-(6-nitrobenzotriazol-l-yl)methanethione (3.11d). Orange

needles (69%), mp 174 oC. H NMR 6 7.46 (d, J= 8.7 Hz, 2H), 7.82 (d, J= 8.7 Hz, 2H),

7.93 (d, J= 8.7 Hz, 1H), 8.02 (d, J= 8.7 Hz, 2H), 9.00 (d, J= 1.8 Hz, 1H). 13C NMR 6

114.3, 114.7, 121.1, 123.4, 123.9, 130.9, 131.4, 136.4, 150.2, 166.0, 208.0. Anal. Calcd.

For C13H7N504S: C, 47.42; H, 2.14 ; N, 21.27. Found C, 47.50; H, 2.02 ; N, 20.93.

(4-Methoxyphenyl)-(6-nitrobenzotriazol-l-yl)methanethione (3.11e). Orange

needles (66%), mp 162 oC. H NMR 6 3.93 (s, 3H), 6.98 (d, J= 9.0 Hz, 2H), 7.86 (d, J=









9.0 Hz, 2H), 8.31 (d, J= 9.0 Hz, 1H), 8.42 (dd, J= 9.0 Hz, 2.1 Hz, 1H), 9.37 (d, J = 2.1

Hz, 1H). 13C NMR 6 55.8, 112.0, 113.9, 112.1, 133.3, 134.0, 134.7, 148.6, 148.9, 164.8,

198.4. Anal. Calcd. For C14H10N403S: C, 53.50; H, 3.21; N, 17.82. Found C, 53.61; H,

3.14; N, 17.62.

(4-Bromophenyl)-(6-nitro-benzotriazol-l-yl)methanethione (3.11f). Orange

micro-crystals (45 %), mp 170 C. H NMR 6 7.67-7.74 (m, 4H), 8.39 (d, J= 9 Hz, 1H),

8.52 (dd, J= 9, 1.8 Hz, 1H), 9.54 (d, J= 2.1 Hz, 1H). 13C NMR 6 112.1, 121.4, 121.9,

128.8, 131.6, 132.1, 132.8, 140.6, 149.0, 149.1, 199.6. Anal. Calcd. For C13H7BrN402S:

C, 42.99; H, 1.94. Found: C, 42.81; H, 1.79.

(6-Nitrobenzotriazol-l-yl)-l-hexylthioamide (3.11g). Yellow microcrystals

(53%), mp 94-97 C. H NMR 0.94 (t, J= 6.9 Hz, 3H), 1.37-1.52 (m, 4H), 1.95-2.05

(m, 2H), 3.78 (t, J= 7.5 Hz, 2H), 8.30 (d, J= 9.0 Hz, 1H), 8.44 (dd, J= 9.0, 1.8 Hz, 1H),

9.79 (d, J= 2.1 Hz, 1H). 13C NMR 6 13.9, 22.3, 29.4, 31.1, 47.6, 113.1, 121.2, 121.8,

131.7, 149.1, 149.4, 210.7. Anal. Calcd. For C12H14N402S: C, 51.78; H, 5.07; N, 20.13.

Found: C, 52.14; H, 5.12; N, 19.79.

(6-Nitrobenzotriazol-l-yl)thiophen-2-yl methanethione (3.11h). Orange

microcrystals (81%), mp 134 C. 1HNMR 6 7.25 (dd, J= 4.0, 1.2 Hz, 1H), 7.97 (d, J=

4.8 Hz, 1H), 8.10 (d, J= 4.0 Hz, 1H), 8.31 (d, J= 8.7 Hz, 1H), 8.42 (d, J= 8.7 Hz, 1H),

9.45 (s, 1H). 13C NMR 6 112.3, 121.2, 121.4, 129.2, 133.0, 136.5, 140.5, 146.6, 148.7,

187.3. Anal. Calcd. For Cl1H6N402S2: C, 45.51; H, 2.08, N, 19.30. Found: C, 44.66; H,

1.90; N, 18.45.









3.4.3 General Procedure for the Preparation of Thionoesters 3.12a-c.

The appropriate alcohol (0.5 mmol) and Et3N (0.05 g, 0.5 mmol) were added to the

respective thiocarbonyl-6-nitrobenzotriazole 3.11a-h dissolved in CH2Cl2 (30 mL) at rt.

Stirring was continued overnight, then solvent was removed by rotary evaporation. The

residue was redissolved in EtOAc (100 mL), washed with 5% Na2CO3 solution (3 x 100

mL), 1M HC1 (2 x 100 mL), water, and brine. The collected organic layers were dried

with Na2SO4, and the solvent was removed under vacuum. Recrystallization from EtOAc/

hexanes afforded thionoesters 3.12a-c.

O-Naphth-l-yl 4-methoxythiobenzoate (3.12a). Yellow needles (88%), mp 93-95

oC. 1HNMR 6 3.91 (s, 3H), 6.98 (d, J= 9.0 Hz, 2H), 7.24-7.27 (m, 1H), 7.44-7.56 (m,

3H), 7.80 (t, J= 6.3 Hz, 2H), 7.90 (d, J= 7.8 Hz, 1H), 8.49 (d, J= 9.0 Hz, 2H). 13C NMR

6 55.7, 113.7, 119.0, 121.6, 125.4, 126.4, 126.6, 126.8, 128.2, 131.0, 131.8, 134.8, 151.0,

164.3, 209.6. Anal. Calcd. For C18H1402S: C, 73.44; H, 4.79. Found: C, 72.65; H, 4.89.

O-Naphth-l-yl 4-nitrothiobenzoate (3.12b). Red needles (99%), mp 139-140 oC.

H NMR 6 7.28 (d, J= 7.5 Hz, 1H), 7.46-7.59 (m, 3H), 7.73 (d, J= 8.4 Hz, 1H), 7.86 (d,

J= 8.4 Hz, 1H), 7.94 (d, J= 7.8 Hz, 1H), 8.35 (d, J= 9.0 Hz, 2H), 8.61 (d, J= 9.0 Hz,

2H). 13C NMR 6 118.6, 121.0, 123.6, 125.4, 126.1, 126.75, 126.84, 127.0, 128.4, 130.2,

134.8, 141.7, 150.4, 150.5, 207.2. Anal. Calcd. For C17HllNO3S: C, 66.01; H, 3.58; N,

4.53. Found: C, 66.07; H, 3.47; N, 4.45.

O-Naphth-l-yl 2-thienylcarbothioate (3.12c). Yellow needles (62%), mp 97-98

oC. 1H NMR 6 7.08 (dd, J= 4.8, 3.9 Hz, 1H), 7.24 (d, J= 7.5 Hz, 1H), 7.39-7.49 (m,

3H), 7.57 (dd, J= 4.8, 1.2 Hz, 1H), 7.75 (d, J= 8.4 Hz, 1H), 7.81-7.85 (m, 2H), 8.07 (dd,

J= 3.9, 1.2 Hz, 1H). 13C NMR 6 119.3, 121.6, 125.5, 126.8, 126.9, 128.4, 128.8, 132.9,






41


134.8, 135.3, 144.8, 150.3, 201.7. Anal. Calcd. For C15HioOS2: C, 66.64; H, 3.73.

Found: C, 66.23; H, 3.71.














CHAPTER 4
SYNTHESES AND CHARACTERIZATION OF ENERGETIC MATERIALS

4.1 Introduction

This chapter is a summary of work completed in collaboration with the US Army

on the synthesis and characterization of energetic materials. Three projects are presented:

synthesis and characterization of (i) blowing agents, (ii) hypergolic agents and (iii)

dinitro substituted five-membered heterocycles.

4.1.1 Synthesis and Characterization of Blowing Agents

The rubber industry employs blowing agents (gas generating agents), such as

dinitropentamethylenetetramine and p-tolysulfonylhydrazide, in the production of

microcellular rubber.37 Azodicarbonamide, Exocerol 232, and Hyderocerol BIH are

blowing agents that are now commonly used in the plastics industry replacing CFCs to

produce polymer foams.38-40 Another significant application of blowing agents is their use

in propellant formulations.443

In a collaborative effort with the US Army, development of novel munition

formulations was investigated. This sub-section details the synthesis and characterization

of energetic compounds to provide new blowing agents. The US Army has previously

applied blowing agents (e.g. 2,4-dinitrophenylhydrazine) as energetic material additives

in explosive mixtures to modify general munition properties. Inclusion of blowing agents

that display separate isotherms from the other components in the explosive mixture is a

method of tempering the violence of the explosion. For a particular Army formulation

containing trinitrotoluene (TNT) and cyclotrimethylenetrinitramine (RDX), inclusion of









blowing agents possessing a DSC of -180 C provides a means of bursting open any

confinement before the reaction of the main constituents, thus mitigating cook off

violence.

Of particular interest are blowing agents with the following characteristics: quick

generation of gas, mp higher than 75 C, stable, and with DSC analysis that indicates gas

evolution at 140-200 C. Stable blowing agents 4.1-4.4 (utilized in the plastics and

rubber industry) are reported to possess the required melting points and suitable DSCs

(Figure 4-1) .39, 84-87

0 0 0 0
H2N N=N NH2 Me-NI N-Me
NO NO
ADCA Nitrosan
(mp 200-206 C) (mp 118 OC)
DSC 225 C DSC 145 C
4.1 4.2

ON
N-N / N

NN N
PT H N
PT
(mp 215 C) NO
DSC 221-243 C DNPT
4.3 DSC 195 C
4.3
4.4
Figure 4-1. Blowing agents with reported melting points and DSCs.

The literature reports syntheses of other energetic additives 4.5-4.7 that possess

measurable melting points, but have not been analyzed by TGA analysis (Figure 4-2).88

To obtain TGA data for the evaluation of energetic additives 4.5-4.7 as blowing agents,

development of reasonable syntheses that could potentially be scaled up to provide 50-

100 g quantities of these compounds was undertaken. Pyrazolium nitrate 4.8 was an

accidental discovery in that it was a byproduct in the attempted synthesis of 3,4-









dinitropyrazole. The nitrate salt of pyrazole was easily obtained from the reaction

mixture by recrystallization. This compound was also thought to be a good blowing

agent candidate so testing was conducted on this nitrate salt.


N N

N
S, 02
02 2
4.5 \ 4.6


-C CNH+ -0
NH N 0

4.7 NNS 4.8
Figure 4-2. Energetic Additives without reported TGA analysis.

4.1.2 Syntheses of Hypergolic Agents

Hypergolic agents are compounds that can be used as fuels and oxidizers which

ignite on contact with one another and therefore do not need a source of ignition.44 These

agents have found many uses in rocketry for both manned and unmanned space flight,

mainly due to their easy start and restart capability.44 Hypergolic propellants have

advantages over other propellants such as cryogenics in that they are easily stored and are

relatively inert until they are in contact with the other agent.45 Since hypergolic

propellants do not need an ignition source they are often the propellant of choice for

spacecraft and satellites as they are required to stop and start their engines thousands of

times over the design life of the vehicle, thereby eliminating one source of possible

failure.45

Hypergolic compounds are employed in liquid bipropellant rocket propulsion

systems which consist of gas generators, separate tanks for the storage of the hypergolic

fuel and oxidizer, and lastly the engine. Operation of the propulsion system begins when









the gas generators have been initiated and the gases from the gas generator pressurize the

fuel tanks. When the oxidizer and fuel valves open, the pressurized oxidizer and fuel

tanks force the propellants through the plumbing and into the engine. Upon contact with

one another the hypergolic fuel and oxidant spontaneously combust through an oxidation

reaction thereby creating propulsion without an ignition source.97

The most common hypergolic fuels currently in use by various space agencies

(USA, Russia and China) are hydrazine, monomethyl hydrazine (MMH) and

unsymmetrical dimethyl hydrazine (UDMH).98 The most common oxidizers are nitrogen

tetroxide, inhibited fuming red nitric acid (IRFNA), nitric acid, chlorine trifluoride, and

concentrated hydrogen peroxide.99 Monomethyl hydrazine MMH and nitrogen tetroxide

were used in the core liquid propellant stages of the Titan family of launch vehicles and

on the second stage of the Delta rocket. The Space Shuttle orbiter uses hypergolic agents

in its Orbital Maneuvering Subsystem (OMS) for orbital insertion, major orbital

maneuvers and deorbit.89 Inhibited red fuming nitric acid (IRFNA) type III B,

monomethyl hydrazine (MMH) are currently the most common oxidizers for use in

bipropellant rocket propulsion systems.99

Traditional hypergolic propellants, such as IRFNA, nitrogen tetroxide, and

members of the hydrazine family are very energetic, but also toxic and/or carcinogenic.

Due to these hazards, such propellants are dangerous to people, they are also expensive

and hazardous to transport, handle and use. As such, there has been a desire to find non-

toxic hypergolic fuels. The US Army is conducting research on suitable replacements for

MMH and its derivatives by conducting thermal analysis on various tertiary diamines.









In a collaborative effort with the US Army, research was conducted to develop

reasonable synthetic routes to the following hypergolic fuels which can potentially be

scaled-up to provide 50-100 g quantities (Figure 4-3). These potential hypergolic fuels

were then shipped to Picatinny arsenal for US Army engineers to conduct thermal

analysis to be completed in the near future.

Me Me
I I
MeN Me

'Me Me Me
4.9 4.10 4.11 4.12
Figure 4-3. Hypergolic fuels.

Previously 1,3-dimethylhexahydropyrimidine 4.10 and 1,3-dimethylimidazoline 4.9

were synthesized by condensation of the corresponding diamines 4.18 90, 4.2091 with

formaldehyde (Scheme 4-1). Stien also reported the synthesis of 1,3-dimethyl-

imidazoline 4.9 by reducing 1,3-dimethylimidazolidin-2-one 4.22 with LAH at room

temperature in a yield of 58 % (Scheme 4-1).92

HCOH
N ._- CH3NH(CH2)nNHCH3
(N] 80% (crude)
0 N 4.18 n=3
4.20 n=2

HCOH1 26%

O
0 LAH, rt
N N-- ether N /N-
4.22 \_ -- 4.9
58%

Scheme 4-1. Synthesis of 4.10 and 4.9.

Dimethyl-(2-pyrrolidin-l-yl-ethyl)amine was previously synthesized by reacting

pyrrolidine with 2-chloro-N,N-dimethylethanamine hydrochloride to form the desired









product in only 12% yield.95 The yield was too low to scale up to 50-100 g quantities for

the US Army so a novel synthetic strategy had to be devised (Scheme 4-2).

(CH3)2N(CH2)2CI HCI

12%
4.11
Scheme 4-2. Synthesis of dimethyl-(2-pyrrolidin-l-yl-ethyl)amine 4.11.

4.1.3 Synthesis of Dinitro-Substituted Five Membered Heterocycles

Dinitro derivatives of five-membered heterocycles may be of interest as energetic

materials and/or possible blowing agent candidates. They have also been shown to have

diverse biological activity, for example 2,4-dinitroimidazole derivatives have been shown

to be very effective agents in increasing the sensitivity of hypoxic cells toward irradiation

in cancer radiotherapy.46 Numerous dinitro heterocycles have also been shown to be

useful intermediates, for instance Padwa recently converted dinitrofuran to various

polysubstituted phenols through SnAr nucleophilic substitution reactions.47

The aim of the present work is the development of reasonable syntheses of dinitro

substituted five-membered heterocyclic compounds. Literature methodologies for the

general preparation of dinitro substituted five-membered heterocycles are scarce. Several

literature examples based on direct nitration of heterocyclic rings result in mixtures of

isomers, which are often difficult to separate.93ab

4.2 Results and Discussion

4.2.1 Results Syntheses and Characterization of Blowing Agents

Various 2-substituted benzo[1,2,3,4]thiatriazine-1,1-dioxides 4.5-4.7 were prepared

following a procedure by Ullmann et al. starting from 2-nitrosulfonyl chloride (4.13)

(Schemes 4-3, 4-4, 4-5).88









Synthesis of 2-phenylbenzo[ 1,2,3,4]thiatriazine- 1,1-dioxide 4.5 was carried out

starting from 2-nitrosulfonyl chloride (4.13) (Scheme 4-3). Condensation of the sulfonyl

chloride with phenylamine gave sulfonamide 4.14a in 82 % yield. Baeyer reduction of

the nitro group provided 2-amino-N-phenylbenzenesulfonamide (4.15a) in 92 % yield,

which was then cyclized to 2-phenylbenzo[1,2,3,4]thiatriazine-1,1-dioxide 4.5 in 75 %

yield by reaction with HONO generated in-situ.

NO2 NO2
N022 SnC2, HCI
O Ph-NH2 HN-Ph S 2, HCI
S I pyridine- \_ S/ 2 EtOH

4.13 4.14a
NH2 N=N
HN-Ph HCI, NaNO2 N-Ph
SO2 \ SO2

4.15 a 4.5
Scheme 4-3. Synthesis of 2-phenylbenzo[1,2,3,4]thiatriazine-1,1-dioxide 4.5.

Similarly, 4.6 was prepared in 74 % yield by cyclization of 4.15b with HONO.

(Scheme 4-4). Sulfonamide 4.14b was prepared in 70 % yield by the reaction of 2-

nitrosulfonyl chloride (4.13) with mesitylamine.

NOO2 O2u e
/ N0 mesitylamine SnC HCI
S02CI\ s
pyridine M2 Me EtOH
SMe Me
Me N=N



Me
4.15b 4.6
Scheme 4-4. Synthesis of compound 4.6.

Bis-benzo[1,2,3,4]thiatriazine-1,1-dioxide 4.7 was obtained in 68 % yield from

4.15c (Scheme 4-5). Two equivalents of sulfonyl chloride 4.13 were reacted with









ethylenediamine to give sulfonamide 4.14c in 93% yield. Upon reduction, sulfonamide

4.14c provided 4.15c in 92 % yield, which was cyclized with HONO to provide 4.7.

NOO
SNO2 H2N-- NH2 H 02 N02
SO2CI Et3N 02 N
4.13 S02H 2 4.
4.14c
a NH2
H 02 NH2 N-N 02S
SN N S.b HCI, NaN02 / N- N
02 N' Ns N
4.15 02
4.7
Scheme 4-5. Synthesis of bis-benzo[ 1,2,3,4]thiatriazine- 1,1-dioxide 4.7.

TGA analysis (50C to 300 oC, rate: 20 oC/min.) of benzo[1,2,3,4]thiatriazine-1,1-

dioxides (4.5, 1.545 mg; 4.6, 0.783 mg; 4.7, 0.345 mg) showed a trend of gradual

decomposition (Figure 4-4). 2-Phenylbenzo[1,2,3,4]thiatriazine-1,1-dioxide 4.5 showed

the sharpest loss in mass, losing 30% from 210 C to 265 C. While 4.7 steadily

decomposed, 4.6 decomposed in stages starting from 100 C with plateaus from 110-

130 C and 140-190 C. Compound 4.5 is the most promising among this series (4.5-4.7),

since it demonstrated the sharpest decomposition.

Unfortunately it was found that upon storing at room temperature for extended

periods of time compounds 4.5-4.7 decomposed into complex mixtures. Since blowing

agents must be stored in munitions casings under diverse temperature ranges these

compounds would be of no use a energetic additives.

Originally pyrazolium nitrate 4.8 was formed as a byproduct in the attempted

dinitration of pyrazole from a previous route established in the Katritzky group.94 Upon

adding ethyl acetate to the reaction mixture it was found that small microcrystals formed,

and NMR, CHN analysis and X-ray crystallography showed that the byproduct was

pyrazolium nitrate. Unfortunately it was also found that the reaction between pyrazole










4.16 and concentrated nitric acid in trifluoroacetic anhydride gave an inter-chelating

molecular complex of 4-nitropyrazole and oxalic acid 4.17 not 3,4-dinitropyrazole

(Scheme 4-6).





100 I







44.
02


IpIL







75-





Figure 4-4. TGA analysis of compounds 4.5-4.7.

SH No- H
N H 3 H
N TFAA N H r N'NH+ HO 0 H
HN03 / + \HNHH
4.16 4.8 O2N O OH

4.17 NO2
Scheme 4-6. Synthesis of inter-chelating molecular complex of 4-nitropyrazole and
oxalic acid 4.17.

This result is consistent with CHN data (Calcd for CsHsN6Os: C, 30.39; H, 2.55; N,

26.58. Found: C, 30.54, H, 2.72; N, 30.85), and X-ray analysis which shows that the

structure is a complex of 2 molecules of 4-nitropyrazole and 1 molecule of oxalic acid

(Figure 4-5). It is believed that oxalic acid arises from the hydrolysis of trifluoroacetic

acid.











02
03A

04A
N3N2
C4A
C2


C4 Ci 01
04


03
C3
N2

Figure 4-5. X-ray of molecular complex of 4-nitropyrazole and oxalic acid 4.17.

While this result was not expected it was believed that pyrazolium nitrate could be

a viable blowing agent candidate.

TGA analysis of 1.4052 mg of the pyrazolium nitrate 4.8 showed a decline in mass

before 160 C. Thus it is not a good candidate for the specifications of a blowing agent,

although it may be suitable for other Army applications (Figure 4-6). The calculated heat

flow for the nitrate salt is +0.35 W/mmol.






r\ \1 n i
;--i


C 40-- -10
N a









20 I-25
C- 2i


S100 10 200 25
Eo UP Temperatur (C) UM IUnwVM VE TAImtm

Figure 4-6. TGA and DSC analysis of pyrazolium nitrate 4.8.









4.2.2 Results Synthesis of Hypergolic Agents

The first attempted synthesis of 1,3-dimethylhexahydropyrimidine 4.10 was

achieved in 72% yield by the treatment of N-methyl-N-[3-(methylamino)propyl]amine

4.18 with formaldehyde 4.19 in water at room temperature for 18 h (Scheme 4-7).

Me Me

NH + HCOH -H2 N
N RT, 18h NM
[: 'Me 0 Me
4.18 4.19 4.10
Scheme 4-7. Synthesis of cyclic aminal 4.10 from formaldehyde.

While this methodology worked well it used the relatively expensive reagent N-

methyl-N-[3-(methylamino)propyl]amine. These reaction conditions also failed to

produce 1,3-dimethyl-imidazoline 4.9 when N,N-dimethylethane-1,2-diamine 4.20 was

reacted with formaldehyde 4.19 (Scheme 4-8).

Me Me

NH HCHO C )
S 4.19
Me Me
4.20 4.9
Scheme 4-8. Synthesis of cyclic aminal 4.9 from formaldehyde.

Another methodology for the preparation of 1,3-dimethylhexahydropyrimidine 4.10

by the reduction of 1,3-dimethyltetrahydropyrimidin-2-one 4.21 with 1.15 equivalents of

LAH in ether under reflux for 12 h afforded a 99 % yield. This provided a cheap source

of starting material (1,3-dimethyltetrahydropyrimidin-2-one 4.21) and better conditions

for isolation of the desired product by simply evaporating ether under reduced pressure

(Scheme 4-9). The conditions established by Johannes and Turid in which the cyclic urea

4.21 was reduced with LAH at room temperature gave a complex mixture, perhaps









because LAH oxidized before the reaction could take place or it was not soluble enough

at room temperature.90

0
Me'N NMe DiethylEther Me'N NMe
+ 1.15 LAH .
4.21 Reflux, 12 h 4.10
Scheme 4-9. Synthesis of cyclic aminal 4.10 via reduction with LAH.

This methodology also reduced 1,3-dimethylimidazolidin-2-one 4.22 into 1,3-

dimethyl imidazoline 4.9 in 80% yield (Scheme 4-10).

0
Me.N NMe Diethyl Ether MeN N-Me
+ 1.15 LAH -
4-. Reflux, 12 h
4.22 4.9
Scheme 4-10. Synthesis of cyclic aminal 4.9 via reduction with LAH.

N,N-Dimethyl-2-(1-pyrrolidinyl)-l-ethanamine 4.11 was obtained by the reaction

of 2.3 equivalents of LAH and 1-[2-(dimethylamino)ethyl]dihydro- 1H-pyrrole-2,5-dione

4.25 in ether under reflux for 12 h in 87 % yield. Intermediate 4.25 was prepared by

treatment of succinic anhydride 4.23 with dimethylaminoethylamine 4.24 in a microwave

synthesizer at 100 watts and 130 C for 5 minutes followed by distillation to give the

product 4.25 in 39 % yield (Scheme 4-11). This methodology was superior to the

previous literature method established by Ried who reacted pyrrolidine with 2-chloro-

N,N-dimethylethanamine hydrochloride to obtain only a 12% yield.95


Me-.NMe Me-N"Me
Me \,

r\ \0 H2N NMe \
O 23 H2N4.24 N 0 LAH, ether N
ji23 4.25 Reflux, 12 h 4.11

Scheme 4-11. Synthesis of N,N-dimethyl-2-(1-pyrrolidinyl)- 1-ethanamine 4.11.









1,3-(Dipyrrolidyl)propane 4.12 was prepared in 43% yield by the reaction of 4

equivalents pyrrolidine 4.26 with 1,3-dibromopropane 4.27 using a procedure by Gero

(Scheme 4-12).96

H
4 + BNB benzene
4 Br / Br 24 h, rt ^
4.26 4.27 4 h, reflux 4.12
Scheme 4-12. Synthesis of 1,3-(dipyrrolidyl)propane 4.12.

4.2.3 Results Nitration of Five Membered Heterocycles

The direct dinitration of 2-ethylthiophene 4.28 was accomplished with HN03 in

TFAA at 0 oC for 12 h. It was found that this reaction proceeds regioselectively to the

desired dinitro derivative 4.29 in a yield of 37% (Scheme 4-13).

02N
n/^ H HN03
STFAA NO2
4.28 4.29
Scheme 4-13. Synthesis of 2-ethyl-3,5-dinitrothiophene 4.29.

Attempts to extend the standard reaction conditions for dinitration of 2-

bromothiophene gave a complicated mixture of nitro substituted derivatives. The

commercially available mixture of 2- and 3-mononitrothiophenes 4.30-4.31 was reacted

with ammonium nitrate in trifluoroacetic anhydride at room temperature for 16 h to yield

a mixture of 2,4- 4.32 and 2,5-dinitrothiophenes 4.33 in high yield (91%). Analysis of

the 1H NMR spectra for the mixture showed a singlet at 6 7.27 which is characteristic for

2,5-dinitrothiophene and a doublet of doublets characteristic for 2,4-dinitrothiophene at 6

8.44. Integration of these two peaks gave a ratio of 1.5:1 for 2,4-dinitrothiophene and

2,5-dinitrothiophene. The mixture melts at 53.1-54.0 oC and might be a good candidate

as an energetic additive (Scheme 4-14).









NO2 NO2
NH4NO3 /. \7
NO2 + 0H 02N + O2N NO2
S 6TFA,TFAA
4.30 ratio 6 :1 4.31 4.32 4.33
ratio 1.5:1
overall yield 91%
Scheme 4-14. Synthesis of mixture of 2,4- 4.32 and 2,5-dinitrothiophenes 4.33.

4.3 Conclusion

This chapter summarizes the work accomplished in collaboration with the US

Army on the synthesis and characterization of broadly defined energetic materials. The

work on blowing agents included thermogravimetric analysis in order to gauge their

usefulness as blowing agents, unfortunately none of the synthesized agents were

applicable as blowing agents due to either being unstable at room temperature 4.5-4.7 or

undergoing undesirable thermal decomposition profiles 4.8. Four hypergolic compounds

4.9-4.12 were synthesized and the methodologies used for compounds 4.9-4.11 improved

upon the previous literature methods by providing higher yields and easier isolation of

the compounds. Dinitration of five membered rings is preliminary work but the two

examples listed have the advantage of being simple, one step procedures with yields

ranging from moderate to excellent. More examples of di-nitrosubstituted five membered

heterocycles are planned for synthetic study in the future.

4.4 Experimental

Caution! Although we have not experienced any problems in synthesizing or

handling these compounds, proper safety precautions should be followed and these

materials should be treated with extreme care.

Melting points were determined using a Bristoline hot-stage microscope and are

uncorrected. 1H (300 MHz) and 13C (75 MHz) NMR spectra were recorded on a 300









MHz NMR spectrometer in DMSO-d6 or chloroform-d solution as indicated. THF was

distilled from sodium-benzophenone ketal prior to use. Column chromatography was

performed on silica gel (300-400 mesh). Elemental analyses were performed on a Carlo

Erba-1106 instrument. For the DSC and TGA experiments a Perkin Elmer DSC 7 or

Perkin-Elmer TGA 7 were used to analyze samples (-3 mg) with a heating rate of 10 or

20 C/min in an argon atmosphear with a flow rate of 50 mL/min. Thermal calibrations

for differential scanning calorimetry were made using indium and freshly distilled n-

octane as references. Heats of fusion were referenced against indium.

4.4.1 General Procedure for the Preparation of Benzo[1,2,3,4]thiatriazine-l,1-
dioxides 4.5-4.6

Sodium nitrite (0.36 g, 5.2 mmol) was added to a stirred solution of the

corresponding sulfonamide (3.5 mmol) dissolved by gentle warming in aqueous acetic

acid 95% (50 mL) and then cooled to 25 C. The resulting mixture was stirred at 25 C

for 8 hours, then ice-cold water (200 mL) was added and the precipitated product was

filtered and washed with water. The red solid was dried in vacuo overnight to afford a

75% yield of 2-phenyl-2H-benzo[ 1,2,3,4]thiatriazine- 1,1-dioxide and 74% of 2-(2,4,6-

Trimethyl-phenyl)-2H-benzo[ 1,2,3,4]thiatriazine-1,1-dioxide.

2-Phenyl-2H-benzo[1,2,3,4]thiatriazine-l,l-dioxide (4.5) Red microcrystals

(75%) mp 101.0C, (Lit. mp 111 C).52 1H NMR 6 7.98-8.03 (m, 2H), 7.54-7.59 (m, 1H),

7.39-7.44 (m, 1H), 7.29-7.34 (m, 1H), 7.03-7.25 (m, 3H).13C NMR 6 135.5, 132.5,

128.4, 130.4, 129.1, 125.4, 125.3, 125.0, 122.1, 120.6.

2-(2,4,6-Trimethylphenyl)-2H-benzo[1,2,3,4]thiatriazine-1,1-dioxide (4.6) Red

microcrystals (74%) mp 151.0 oC, (Lit. mp 150 C).52 1HNMR 6 8.09-8.14 (m, 1H),









7.91-7.96 (m, 1H), 7.80-7.86 (m, 1H), 2.35 (s, 3H), 2.29 (s, 6H). 13C NMR 6 141.5,

140.7, 138.9, 134.0, 132.8, 130.3, 129.8, 127.7, 129.6, 120.6, 21.1, 18.3.

4.4.2 General Procedure for the Preparation of Pyrazolium Nitrate 4.8

Trifluoroacetic anhydride [6.5 mL] was added to 1-H pyrazole [ 0.68 g,10 mmol]

under vacuum and chilled in an ice bath. Concentrated nitric acid [2.2 mL] was added

0.5 mL increments very slowly (-45 minutes) to the mixture. After stirring for 12 h at

room temperature, ethyl acetate (50 mL) was added to the reaction mixture and then

stored in freezer 3 hours until the byproduct precipitated out as white crystals which were

then filtered off. Note: this was step was repeated as necessary until no byproduct was

evident after freezing the mixture. (0.65 g, Yield=50%) precipitated off as white

microcrystals.

Pyrazolium nitrate (4.8) White microcrystals (50%). 1H NMR 6 8.59 (s, 1H),

12.21 (s, 1H). 13C NMR 6 32.5, 134.1, 135.5.

4.4.2.1 General Procedure for the Preparation of Hypergolic Aminals 4.9 and 4.10.

The corresponding cyclic urea (16.8 mmol) was added dropwise to a solution of

LAH (0.80g, 19.2 mmol) in diethyl ether (160 mL). The mixture was then refluxed

gently for 12 hr. Water (5mL) was added slowly then 2N NaOH (2mL) solution was

added dropwise to quench the reaction. The solid was then filtered off and diethyl ether

was removed under reduced vacuum to afford 1,3-dimethylimidazolidine (1.46 g) in a

yield of 80% and 1,3-dimethylhexahydropyrimidine (1.91 g) in a yield of 99%.

1,3-Dimethylimidazolidine (4.9) Clear oil (80%) bp 111 C/760 mm Hg, (lit bp

110 C/760 mm Hg).57 1H NMR 6 2.25 (s, 6H), 2.63 (s, 4H), 3.15 (s, 2H). 13C NMR 6

41.5, 54.3, 79.8.









1,3-Dimethylhexahydropyrimidine (4.10) Clear oil (99%) bp 131 C/760 mm Hg,

(lit bp 126 C/760 mm Hg).56 1H NMR 61.69 (m, 2H), 2.24 (s, 6H), 2.40-2.43 (m, 4H),

2.97 (br s, 2H). 13C NMR 6 23.9, 43.1, 54.1, 79.6

4.4.2.2 General Procedure for the Preparation of Hypergolic Agent Dimethyl(2-
pyrrolidin-1-yl-ethyl)amine 4.11

1-(2-Dimethylaminoethyl)pyrrolidine-2,5-dione (4g, 23.5 mmol) was added to a

solution of LAH (2.04g, 54.05 mmol) in ether. The mixture was refluxed overnight

under nitrogen then the mixture was quenched with water and the organic layer was

filtered off. Ether was removed under reduced pressure to afford dimethyl-(2-pyrrolidin-

1-yl-ethyl)amine (2.91 g) in a yield of 87%.

N,N-Dimethyl-2-(1-pyrrolidinyl)-l-ethanamine (4.11) Clear oil (87%) bp 170.9

C/760 mm Hg, (lit bp 56.5 C/1.5 mm Hg).64 1H NMR 61.70-1.74 (m, 4H), 2.19 (s, 6H),

2.35-2.40 (m, 2H), 2.47-2.54 (m, 6H). 13C NMR 6 21.4, 43.9, 52.32, 52.34, 56.5.

4.4.2.3 General Procedure for the Preparation of Hypergolic Agent 1,3-
(Dipyrrolidyl)propane 4.12

To a solution of 1,3-dibromopropane (8.35 mL, 21 mmol) and dry benzene (200

mL) was added pyrrolidine (27.02 mL, 84 mmol). The reaction mixture was stirred at

room temperature for 12 hours then the mixture was refluxed for 4 hours on a hot water

bath, cooled and filtered from pyrrolidine bromide. Benzene was removed under reduced

vacuum to afford 1,1'-(1,3-propanediyl)bis-pyrrolidine (6.5g, 43% yield).

1,3-(dipyrrolidyl)propane (4.12) Clear oil (43%) bp 111C/760 mm Hg, (lit bp

110 C/760 mm Hg).65 1H NMR 61.70-1.70 (m, 10H), 2.45-2.50 (m, 12H). 13C NMR

23.5, 28.8, 54.4, 55.0.









4.4.3 General Procedure for the Preparation of 2-Ethyl-3,5-Dinitrothiophene 4.29

Trifluoroacetic anhydride (2.9 mL) was added to 2-ethylthiophene (0.56 mL, 5

mmol) under vacuum and chilled in an ice bath. Concentrated nitric acid (0.88 mL) was

added in 0.3 mL increments very slowly (-45 minutes) to the mixture. After stirring for

12 h at room temperature, ethyl acetate (50 mL) was added to the reaction mixture and

the organic layer was washed with brine and the organic layer was extracted. Purification

by column chromatography gave 2-ethyl-3,5-dinitrothiophene ( 0.29 g, 37% yield) as a

red oil.

2-Ethyl-3,5-dinitrothiophene (4.29) Red oil (37%). 1H NMR 6 1.48 (t, J=7.5 Hz,

3H), 3.39 (dd, J=7.5 Hz, 2H), 8.36 (s, 1H). 13C NMR 6 13.8, 23.8, 124.5, 141.3, 145.4,

157.4. Anal. Calcd for C6H6N204S: C 35.64, H2.99, N 13.86. Found C 35.82, H 2.83, N

13.57.

4.4.4 General Procedure for the Preparation of 2,4-Dinitrothiophene 4.32, 2,5-
Dinitrothiophene 3.33

Pure 2-nitrothiophene (0.5g, 3.9 mmol) was added dropwise to a solution of

NH4N03 (0.62g, 3.9 mmol) in TFA (1.2 mL) and TFAA (1.1 mL) at 0 C. The reaction

mixture was allowed to warm to room temperature and was stirred for 12 hr. Water was

added to the reaction mixture and the product was filtered off with gravity filtration to

give a mixture of 2,4-dinitrothiophene and 2,5-dinitrothiophene (0.94 g, 91%).

2,4-dinitrothiophene (4.32), 2,5-dinitrothiophene (4.33) (mp 53.1-54.0 oC) 1H

NMR 6 7.27 (s, 1H), 7.87 (s, 1H), 8.44 (dd, J1=1.8, 10.5 Hz, 1H). Anal. Calcd for

C4H2N204: C 27.59, H 1.16, N 16.09. Found C 28.02, H 0.96, N 15.68.














CHAPTER 5
CONCLUSION

The successful application of 1-benzotriazolyl-2-propynones as a novel 1-3-

biselectrophile was demonstrated in Chapter 2. 1-Benzotriazolyl-2-propynones, in

comparison with the literature procedures to synthesize pyrido[1,2-a]pyrimidin-2-ones,

offered shorter reaction times, cleaner conversion to products, and higher yields. 1-

Benzotriazolyl-2-propynones were also successfully reacted with other 1,3-bis-

nucleophiles: 2-picolines, 2-methylquinoline and 2-aminothiazole to form 2H-quinolizin-

2-ones, pyrido[1,2-a]quinolin-3-ones, and thiazolo[3,2-a]pyrimidin-7-one in moderate to

excellent yields.

Several novel thioacyl nitrobenzotriazoles, which were synthesized from a previous

procedure from Rapoport, were shown to be effective thioacylating reagents and a viable

alternative to previous problematic routes. This procedure was compared in conjunction

with another procedure which used a Grignard methodology for the synthesis of thioacyl

benzotrizoles. It was found that the Grignard method is the preferred means of obtaining

arylthiocarbonylbenzotriazoles, while Rapoport's synthesis is preferred for alkyl, alkynyl,

and heteroaryl thiocarbonylbenzotriazoles. To test the thioacylating ability of the new

thioacyl nitrobenzotriazoles synthesized, several were reacted with 1-naphthalenol to

form novel thionoesters. Advantages of thioacyl nitrobenzotriazoles are that they

circumvent the use of unstable or hazardous reagents, the mild conditions employed are

tolerable of a large variety of functional groups and yields are comparable and in many

cases higher than previously reported methods.









Chapter 4 summarizes the work accomplished in collaboration with the US Army

on the synthesis and characterization of broadly defined energetic materials. The work

on blowing agents included thermogravimetric analysis in order to gauge their usefulness

as blowing agents, unfortunately none of the synthesized agents were applicable as

blowing agents, due to either being unstable at room temperature or undergoing

undesirable thermal decomposition profiles. Four hypergolic compounds were

synthesized and the methodologies used for three of the compounds improved upon the

previous literature methods by providing higher yields and easier isolation of the

compounds. Dinitration of five-membered rings is preliminary work, but the two

examples listed have the advantage of being simple, one-step procedures with yields

ranging from moderate to excellent. More examples of dinitrosubstituted five-membered

heterocycles are planned for synthetic study in the future
















LIST OF REFERENCES


1. Katritzky, A.R.; Belyakov Aldchim. Act. 1998, 31(2), 35.

2. Katritzky, A.R.; Lan, X.; Yang J.Z. Chem. Rev. 1998, 98, 409.

3. Reboud, R. M. J. Am. Chem. Soc. 1980, 102(3), 1039

4. a) Katritzky, A. R.; Yannakopoulou, K.; Lue, P.; Rasala, D.; Urogdi, L. J. Chem.
Soc., Perkin Trans. 1 1989, 225. b) Katritzky, A. R.; Pernak, J.; Fan, W.-Q.;
Saczewski, F. J. Org. Chem. 1991, 56, 4439.c) Katritzky, A. R.; Urogdi, L.;
Mayence, A. J. Chem. Soc., Chem. Commun. 1989, 337. d) Katritzky, A. R.;
Takahashi, I.; Fan, W.-Q.; Pernak, J. Synthesis. 1991, 1147. e) Katritzky, A. R.;
Fan, W.-Q.; Black, M.; Pernak, J. J. Org. Chem. 1992, 57, 547.

5. a) Katritzky, A. R.; Long, Q.-H.; Lue, P.; Jozwiak, A. Tetrahedron 1990, 46, 8153.
b) Katritzky, A. R.; Long, Q.-H.; Lue, P. Tetrahedron Lett. 1991, 32, 3597. c)
Katritzky, A. R.; Lan, X.; Zhang, Z. J. Heterocycl. Chem. 1993, 30, 381. d)
Katritzky, A. R.; Barcock, R. A.; Long, Q.-H.; Balasubramanian, M.; Malhotra, N.;
Greenhill, J. V. Synthesis 1993, 233. e) Katritzky, A. R.; Jiang J. J. Org. Chem.
1995, 60, 7597.

6. Katritzky, A. R.; Kuzmierkiewicz, W. J. Chem. Soc., PerkinTrans. 1 1987, 819. b)
Katritzky, A. R.; Yang, Z.; Lam, J. N. J. Org. Chem. 1991, 56,2143. c) Richard, J.
P.; Nagorski, R. W.; Rudich, S.; Amyes, T. L.; Katritzky, A. R.; Wells, A. P. J.
Org. Chem. 1995, 60, 5989. d) Katritzky, A. R.; Yang, Z.; Lam, J. N. Synthesis
1990, 666. e) Katritzky, A. R.; Jiang, J. J. Org. Chem. 1995, 60, 7597

7. Graebe, C.; Ullmann, F. Justus Liebigs Ann. Chem. 1896, 291, 16.

8. Katritzky, A. R.; Kuzmierkiewicz, W.; Greenhill, J. V. Reel. Trav. Chim. Pays-Bas
1991, 110, 369.

9. Katritzky, A. R.; Shobana, N.; Pernak, J.; Afridi, A. S.; Fan, W.Q. Tetrahedron
1992, 48, 7817.

10. Katritzky, A. R.; Perumal, S.; Fan, W.-Q. J. Chem. Soc., Perkin Trans. 2 1990,
2059.

11. Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Org. Chem. 1989, 54, 6022.

12. Katritzky, A. R.; Blitzke, T.; Li, J. Synth. Commun. 1996, 26, 3773.









13. Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Chem. Soc. Perkin Trans. 1 1987,
791.

14. Katritzky, A. R.; Rachwal, S.; Offerman, R. J.; Najzarek, Z.; Yagoub, A. K.;
Zhang, Y. Chem. Ber. 1990, 123, 1545.

15. Bachman, G. B.; Heisey, L. V. J. Am. Chem. Soc. 1946, 68, 2496.

16. Katritzky, A. R.; Jurczyk, S.; Bogumila, R.; Stanislaw, R.; Shcherbakova, I.,
Yannakopoulou, K. Synthesis 1992, 12, 1295

17. Katritzky, A. R.; Wu, J.; Kuzmierkiewicz, W.; Rachwal, S. Liebigs Ann. Chem.
1994, 1.

18. Katritzky, A. R.; Rachwal, S.; Caster, K. C.; Mahni, F.; Law, K. W.; Rubio, O. J.
Chem. Soc., Perkin Trans. 1 1987, 781.

19. Katritzky, A. R.; Rachwal, S.; Rachwal, B. J. Org. Chem. 1994, 59, 5206.

20. Katritzky, A. R.; Zhang, G.; Jiang, J. J. Org. Chem. 1995, 60, 7625.

21. Rees, C. W.; Storr, R. C. J. Chem. Soc. (C) 1969, 1478.

22. Katritzky, A. R.; Li, J.; Malhotra, N. Liebigs Ann. Chem. 1992, 843.

23. Azolides, Organic Synithei And Biochemistry; Baur, H.; Stabb, K.H.; Scneider,
K.M., Eds.; John Wiley and Sons Ltd: New York, 1998.

24. Katritzky, A. R.; Shobana, N.; Pernak, J.; Afridi, A. S.; Fan, W. Q. Tetrahedron
1992, 48, 7817.

25. a) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org. Chem. 2000, 65, 8210. b)
Katritzky, A. R.; Chang, H.-X.; Yang, B. Synthesis 1995, 503. c) Katritzky, A. R.;
Yang, B.; Semenzin, D. J. Org. Chem. 1997, 62, 726. d) Katritzky, A. R.; Pastor,
A.; Voronkov, M. V. J. Heterocycl. Chem. 1999, 36, 777. e) Katritzky, A. R.;
Pastor, A. J. Org. Chem. 2000, 65, 3679.Katritzky, A.R.; Suzuki, K.; Wang Z.
SynnLett 2005, 1656.

26. Katritzky, A. R.; Zhang, Y.; Singh, S. K. Synthesis 2003, 2795.

27. Katritzky, A.R.; Suzuki, K.; Wang Z. SynnLett 2005, 1656.

28. Katritzky, A. R.; Shestopalov, A. A.; Suzuki, K. Synthei, 2004, 1806.

29. Katritzky, A. R.; Suzuki, K.; Singh, S. K. J. Org. Chem. 2003, 68, 5720.

30. Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003, 68, 4932.

31. Katritzky, A. R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003, 68, 1443.









32. Katritzky, A. R.; Wang, Z.; Wang, M.; Wilkerson, C. R.;Hall, C. D.; Akhmedov,
N. G. J. Org. Chem. 2004, 69, 6617.

33. Katritzky, A. R.; Ledoux, S.; Witek, R. M.; Nair, S. K. J. Org. Chem. 2004, 69,
2976.

34. Larsen, C.; Steliou, K.; Harpp, D. N. J. Org. Chem. 1978, 43, 337.

35. Katritzky, A. R.; Witek R.M.; Rodriguez-Garcia V.; Mohapatra P. P.; Rogers J. W.;
Cusido J.; Abdel-Fattah A. A. A.; Steel P. J. J. Org. Chem., 70, 7866, 2005.

36. a) Shalaby, M. A.; Rapoport, H. J. Org. Chem. 1999, 64,1065. b) Shalaby, M. A.;
Grote, C. W.; Rapoport, H. J. Org. Chem. 1996, 61, 9045.

37. Kok, C. M.; Tok, I. F.; Toh, H. K. Plastics and Rubber Processing and
Applications 1985, 5, 281-4.

38. Prasad, A.; Shanker, M. Cellular Polymers 1999, 18, 35-51.

39. Kim, Kwan-Eung; Lee, Keun-Won. Hwahak Konghak 2002, 40, 427-430.

40. Marrucho, I. M.; Oliveira, N. S.; Dohrn, R. J. Chem. Eng. Data 2002, 47, 554-
558.

41. Krabbendam-La Haye, E. L. M.; de Klerk, W. P. C.; Miszczak, M.; Szymanowski,
J. Journal of Thermal Analysis and Calorimetry 2003, 72, 931-942.

42. Niu, Fushui; Ou, Yuxiang; Chen, Boren. Hanneng Cailiao 1997, 5, 153-156.

43. Ou, Yuxiang; Chen, Boren; Yan, Hong; Jia, Huiping; Li, Jianjun; Dong, Shuan.
Journal of Propulsion and Power 1995, 11, 838-47.

44. Grinter, K. (August, 2002). NASA Facts. Retrieved from http://www-
pao.ksc.nasa.gov/kscpao/nasafact/count2.htm Last accessed September 2005.

45. Schooley, M. (n.d.). Fuel Propellants Storable, and Hypergolic vs. Ignitable.
Retrieved from http://www.permanent.com/t-mikesc.htm Last accessed September
2005.

46. Agrawal, K.C.; Bears, K.B.; Sehgal, R.K. J. Med. Chem. 1979, 22, 589.

47. Padwa, A.; Waterson, A. G. ARKIVOC, 2001, (iv), 29.

48. Harriman, G. C. B.; Chi, S.; Zhang, M.; Crowe, A.; Bennett, R. A.; Parsons, I.
Tetrahedron Lett. 2003, 44, 3659.









49. a) Smith, R. L.; Barette, R. J.; Sanders-Bush, E. J. Pharmacol. Exp. Ther. 1995,
275, 1050. b) Awouters, F.; Vermeire, J.; Smeyers, F.; Vermote, P.; Van Beek, R.;
Niemegeers, C. J. E. DrugDev. Res. 1986, 8, 95. c) Matsutani, S.; Mizushima, Y.
Chem. Abstr. 1990, 112, 98557. d) Yanagihara, Y.; Kasai, H.; Kawashima, T.;
Shida, T. Jpn. J. Pharamacol. 1988. 48, 91.

50. a) Hermecz, I.; Kokosi, J.; Podanyi, B.; Liko, Z. Tetrahedron, 1996, 52, 7789. b)
Ferrarini, P.; Mori, C.; Primofiore, G.; Calzolari, L.; J. Heterocyclic Chem. 1990,
27, 881. c) Selic, L.; Strah, S.; Toplak, R.; Stanovnik, B. Heterocycles 1998, 47,
1017. d) Selic, L.; Stanovnik, B. J. Heterocyclic Chem. 1997, 34, 813. e) Ye, F.-C.;
Chen, B.-C.; Huang, X. Syhii/hei, 1989, 4, 317.

51. Dorokhov, V. A.; Baranin, S. V.; Dib, A.; Bogdanov, V. S.; Yakovlev, I. P.;
Stashina, G. A.; Zhulin, V. M. Chem. Abstr. 1991, 114, 101911.

52. Roma, G.; DiBraccio, M. B.; Albi, A.; Mazzei, M.; Ermili, A. J. Heterocyclic
Chem. 1987, 24, 329.

53. Al-Jallo, H. N.; Al-Biaty. I. A. J. Heterocyclic Chem. 1978, 15, 801.

54. Acheson, R. M.; Wallis, J. D. J. Chem. Soc., Perkin Trans. 1 1982, 1905.

55. Doad, G. J. S.; Okor, D. I.; Scheinmann, F.; Bates, P. A.; Hursthouse, M. B. J.
Chem. Soc., Perkin Trans 1 1988, 2993.

56. Suri, O. P.; Suri, K. A.; Gupta, B. D.; Satti, N. K. Synth. Commun. 2002, 32, 741.

57. Kato, T.; Atsumi, T. Chem. Abstr. 1968, 68, 49422g.

58. Murthi, G. S. S.; Gangopadhyay, S. K. Indian J. Chem. 1979, 17, 20.

59. Wahe, H.; Mbafor, J. T.; Nkengfack, A. E.; Fomum, Z. T.; Cherkasov, R. A.;
Sterner, O.; Doepp, D. ARKIVOC 2003, (xv), 107.

60. Nicolaou, K. C.; Sato, M.; Theodorakis, E. A.; Miller, N. D. J.Chem. Soc., Chem.
Commun. 1995, 1583.

61. Barrett, A. G. M.; Lee, A. C. J. Org. Chem. 1992, 57, 2818.

62. Baxter, S. L.; Bradshaw, J. S. J. Org. Chem. 1981, 46, 831. (b) Bradshaw, J. S.;
Jones, B. A.; Gebhard, J. S. J. Org. Chem. 1983, 48, 1127. (c) Jones, B. A.,
Bradshaw, J. S.; Brown, P. R.; Christensen, J.J.; Izatt, R. M. J. Org. Chem. 1983,
48, 2635.









63. (a) Baldwin, S. W.; Haut, S. A. J. Org. Chem. 1975, 40, 3885. (b)Tsurugi, J.;
Nakao, R.; Fukumoto, T. J. Am. Chem. Soc. 1969, 91, 4587. (c) Nagata, Y.;
Dohmaru, T.; Tsurugi. J. J. Org. Chem. 1973, 38, 795. (d) Pettit, G. R.; Piatak, D.
M. J. Org. Chem. 1962, 27, 2127. (e) Maione, A. M.; Torrini, I. Chem. Ind. 1975,
839. (f) Kraus, G. A.; Frazier, K. A.; Roth, B. D.; Taschner, M. J.;
Neuenschwander, K. J. Org. Chem. 1981, 46, 2417.

64. Bunnelle, W. H.; Mckinnis, B. R.; Narayanan, B. A. J. Org. Chem. 1990, 55, 768,
and references therein.

65. Reynaud, P.; El Hamad, Y.; Davrinche, C.; Nguyen-Tri-Xuong, E.; Tran, G.;
Rinjard, P. J. Heterocycl. Chem. 1992, 29, 991.

66. Kraemer, I.; Schunack, W. Arch. Pharm. (Weinheim, Ger.) 1986, 319, 1091.

67. Bhattacharya, B. K.; Singh, H. H.; Yadav, L. D. S.; Hoornaert, G. Acta Chim.
Acad. Sci. Hung. 1982, 110, 133.

68. Meijs, G. F.; Rizzardo, E.; Le, T. P. T.; Chen, Y. Makromol. Chem. 1992, 193, 369.

69. Nielson, D. G. In The Chemistry ofAmidines andlmidates; Patai, S., Ed.; Wiley:
New York, 1975; pp 385-489.

70. (a) Vinkler, P.; Thimm, K.; Voss, J. Liebigs Ann. Chem. 1976, 2083. (b) Voss, J.;
Schmueser, W.; Schlapkohl, K. J. Chem. Res. S (Synopses)

71. (a) Hoffmann, R.; Hartke, K. Chem. Ber. 1980, 113, 919. (b) Kaloustian, M. K.;
Nader, R. B. J. Org. Chem. 1981, 46, 5050. (c) Kantlehner, W.; Haug, E.; Farkas,
M. Liebigs Ann. Chem. 1982, 1582.(d) Nader, R. B.; Kaloustian, M. K.
Tetrahedron Lett. 1979, 20, 1477.

72. Kaloustian, M. K.; Khouri, F. Tetrahedron Lett. 1981, 22, 413.

73. (a) Hedgley, E. J. Brit. Pat. 1,589,128; 7 May 1981.(b) Adiwidjaja, G.; Gu nther,
H.; Voss, J. Angew. Chem., Int. Ed. Engl. 1980, 19, 563.

74. (a) Bu hi, H.; Seitz, B.; Meier, H. Tetrahedron 1977, 33, 449. (b) Seybold, G.;
Heibl, C. Chem. Ber. 1977, 110, 1225.

75. Scheithauer, S.; Mayer, R. Thio- and Dithiocarboxylic Acids and Their Derivatives
in Topics in Sulfur Chemistry; Senning, A., Ed; Thieme: Stuttgart, 1979; Vol. 4.(b)
Lythgoe, B.; Waterhouse, I.; Tetrahedron Lett. 1977, 18, 4223.

76. Pederson, B. S.; Scheibye, S.; Clausen, K.; Lawesson, S.-O. Bull. Soc. Chim.
Belg. 1978, 87, 293.

77. Katritzky, A.R.; He, H-Y.; Suzuki, K. J. Org. Chem. 2000, 65, 8210.









78. Katritzky, A.R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003, 68, 1443.

79. Katritzky, A.R.; Abdel-Fattah, A. A. A.; Wang, M. J. Org. Chem. 2003, 68, 4932.

80. Katritzky, A.R.; Cai, C.; Suzuki, K.; Singh, S. K. J. Org. Chem. 2004, 69, 811.

81. Katritzky, A.R.; Suzuki, K.; Singh, S. K.; He, H-Y. J. Org. Chem. 2003, 68, 5720.

82. (a) Katritzky, A. R.; Moutou, J.-L.; Yang, Z. Synlett 1995, 99. b) Katritzky, A. R.;
Moutou, J.-L.; Yang, Z. Synthesis 1995, 1497.

83. Walter, M.; Radke, M. Liebigs Ann. 1973, 636.

84. Lobbecke S., Pfeil A., Krause H.H., Propellants, Explosives, Pyrotechnics 1999,
24, 168.

85. May W.P., Plastics Technology, 1977, 23(6), 97-105.

86. Tall A., Zeman S., J. ThermalAnalysis, 1977, 12(1), 75.

87. Patil, A. J.; Muthusamy, E.; Mann, S. Angew. Chem. Int. Ed. 2004, 43, 4928.

88. Ullmann, F.; Gross, C. Ber. 1911, 43, 2694.

89. Greene, B.; McClure, M.B.; Johnson, H.T.Chem. H.&S. 2004, 11, 6.

90. Johannes, D.; Turid, S. Act. Chem. Sc. 1991, 45(10), 1064.

91. Yoder, C.H.; Zuckerman, J.J. J. Am. Chem. Soc. 1966, 88, 4831.

92. Bates, H.A.; Condulis, N.; Stien, N.L. J. Org. Chem. 1986, 51, 2228.

93. (a) Maag, H.; Manukian, B. K. Helv. Chim. Acta 1973, 56, 1787. (b) Blatt, A. H.;
Bach, S.; Kresch, L. W. J. Org. Chem. 1957, 22, 1693.

94. Katritzky, A. R.; Scriven, E. F.V.; Majumder, S.; Akhmedova, R.G; Akhmedov,
N. G.; Vakulenko A. V. ARKIVOC 2005, (ii), 179.

95. Rice, L.M.; Grogan, C.H.; Reid, E.E. J. Am. Chem. Soc. 1953, 75, 2261.

96. Gero A. J. Am. Chem. Soc. 1954, 76, 5158.

97. Thompson, D.M. U.S. Patent 6,013,143, 2000.

98. Braeunig, R.A. (n.d.). Rocket Propellants. Retrieved from
http://www.braeunig.us/space/propel.htm Last accessed September 2005.

99. Rusek, J.; Palmer, K.B; Darren M. U.S. Patent 2,005,022,911, 2005.















BIOGRAPHICAL SKETCH

James William Rogers was born in Sandwhich, Illinois, on October 3rd, 1976, to

William Edward Rogers and Barbara Jean Rogers. Shortly after birth, the family moved

to Aurora, Illinois, where they lived for four years. The family then moved to Phoenix,

Arizona, for 2 years, and then moved back to the Midwest to Granite City, Illinois, which

is close to St. Louis, Missouri. William Rogers supported the family by working as a

chemist at Sigma-Aldrich. James Rogers graduated from Granite City Senior High

School in 1995; he lettered varsity in football but academic honors so far eluded him.

James went to college at nearby Southern Illinois University at Edwardsville in the fall

term of 1995. He paid all of his education expenses by working as a waiter at The

Lawyers Club of St. Louis. After receiving a Bachelor of Science in chemistry at age 23,

James began work at Abbott Labs in North Chicago, Illinois, as a QC chemist. After four

months the chemistry department at Southern Illinois called with an offer for admission

to graduate school. He refused at first but after a week of thought decided to enroll and

resigned his position at Abbott Labs. James enrolled in the graduate program at Southern

Illinois in the summer of 2000, working under the tutelage of Professor Tim Patrick,

whose novel research inspired James to continue his education. He received a Master of

Science in chemistry in August of 2002, this time he graduated with high honors and

received an award for outstanding chemical research. James also met his future wife

Hong Yu at Southern Illinois, who also received a Master of Science in chemistry in the

summer of 2002. In the summer of 2002, Hong and James began their PhD study at the






69


University of Florida and were married in 2003. James now works under the mentorship

of Professor Alan Katritzky. On May 22nd, 2005, at 6 AM James and Hong were blessed

by the birth of their daughter, Elaine Yu Rogers.