Citation
Chemistry of aziridines

Material Information

Title:
Chemistry of aziridines
Creator:
Clough, Stuart Chandler, 1943- ( Dissertant )
Deyrup, James A. ( Thesis advisor )
Brey, W. S. ( Reviewer )
Butler, G. B. ( Reviewer )
Bennet, B. F. ( Reviewer )
Battiste, M. C. ( Reviewer )
Place of Publication:
Gainesville, Fla.
Publisher:
University of Florida
Publication Date:
Copyright Date:
1969
Language:
English
Physical Description:
xiv, 114 leaves. : illus. ; 28 cm.

Subjects

Subjects / Keywords:
Anhydrides ( jstor )
Aziridines ( jstor )
Chlorides ( jstor )
Hydrazides ( jstor )
Hydrazines ( jstor )
Ions ( jstor )
Reaction mechanisms ( jstor )
Room temperature ( jstor )
Sodium ( jstor )
Water temperature ( jstor )
Aziridine ( lcsh )
Chemistry thesis Ph. D
Dissertations, Academic -- Chemistry -- UF
Genre:
bibliography ( marcgt )
non-fiction ( marcgt )

Notes

Thesis:
Thesis--University of Florida, 1969.
Bibliography:
Bibliography: leaves 108-113.
Additional Physical Form:
Also available on World Wide Web
General Note:
Manuscript copy.
General Note:
Vita.

Record Information

Source Institution:
University of Florida
Holding Location:
University of Florida
Rights Management:
Copyright [name of dissertation author]. Permission granted to the University of Florida to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
Resource Identifier:
030419607 ( AlephBibNum )
16992044 ( OCLC )
AER8368 ( NOTIS )

Downloads

This item has the following downloads:

chemistryofaziri00clourich ( .pdf )

chemistryofaziri00clourich_Page_057.txt

UF00097753_00001_xml.txt

chemistryofaziri00clourich_Page_110.txt

chemistryofaziri00clourich_Page_074.txt

chemistryofaziri00clourich_Page_091.txt

chemistryofaziri00clourich_Page_038.txt

chemistryofaziri00clourich_Page_068.txt

chemistryofaziri00clourich_Page_003.txt

chemistryofaziri00clourich_Page_119.txt

chemistryofaziri00clourich_Page_014.txt

chemistryofaziri00clourich_Page_031.txt

chemistryofaziri00clourich_Page_026.txt

chemistryofaziri00clourich_Page_027.txt

chemistryofaziri00clourich_Page_025.txt

chemistryofaziri00clourich_Page_090.txt

chemistryofaziri00clourich_Page_044.txt

chemistryofaziri00clourich_Page_048.txt

chemistryofaziri00clourich_Page_045.txt

chemistryofaziri00clourich_Page_009.txt

chemistryofaziri00clourich_Page_010.txt

chemistryofaziri00clourich_Page_007.txt

chemistryofaziri00clourich_Page_080.txt

chemistryofaziri00clourich_Page_061.txt

chemistryofaziri00clourich_Page_101.txt

chemistryofaziri00clourich_Page_116.txt

chemistryofaziri00clourich_Page_107.txt

chemistryofaziri00clourich_Page_055.txt

chemistryofaziri00clourich_Page_118.txt

chemistryofaziri00clourich_Page_043.txt

chemistryofaziri00clourich_Page_097.txt

chemistryofaziri00clourich_Page_076.txt

chemistryofaziri00clourich_Page_017.txt

chemistryofaziri00clourich_Page_087.txt

chemistryofaziri00clourich_Page_041.txt

chemistryofaziri00clourich_Page_008.txt

chemistryofaziri00clourich_Page_126.txt

chemistryofaziri00clourich_Page_046.txt

chemistryofaziri00clourich_Page_022.txt

chemistryofaziri00clourich_Page_129.txt

chemistryofaziri00clourich_Page_036.txt

chemistryofaziri00clourich_Page_069.txt

chemistryofaziri00clourich_Page_083.txt

chemistryofaziri00clourich_Page_098.txt

chemistryofaziri00clourich_Page_078.txt

chemistryofaziri00clourich_Page_084.txt

chemistryofaziri00clourich_Page_120.txt

chemistryofaziri00clourich_Page_075.txt

chemistryofaziri00clourich_Page_012.txt

chemistryofaziri00clourich_Page_095.txt

chemistryofaziri00clourich_Page_109.txt

chemistryofaziri00clourich_Page_013.txt

chemistryofaziri00clourich_Page_102.txt

chemistryofaziri00clourich_Page_054.txt

chemistryofaziri00clourich_Page_063.txt

chemistryofaziri00clourich_Page_030.txt

chemistryofaziri00clourich_Page_021.txt

chemistryofaziri00clourich_Page_113.txt

chemistryofaziri00clourich_Page_050.txt

chemistryofaziri00clourich_Page_081.txt

chemistryofaziri00clourich_Page_125.txt

chemistryofaziri00clourich_Page_042.txt

chemistryofaziri00clourich_Page_105.txt

chemistryofaziri00clourich_Page_049.txt

chemistryofaziri00clourich_Page_029.txt

chemistryofaziri00clourich_Page_096.txt

chemistryofaziri00clourich_Page_015.txt

chemistryofaziri00clourich_Page_089.txt

chemistryofaziri00clourich_Page_028.txt

chemistryofaziri00clourich_Page_106.txt

chemistryofaziri00clourich_Page_073.txt

chemistryofaziri00clourich_Page_072.txt

chemistryofaziri00clourich_Page_040.txt

chemistryofaziri00clourich_Page_079.txt

chemistryofaziri00clourich_Page_005.txt

chemistryofaziri00clourich_Page_108.txt

chemistryofaziri00clourich_Page_034.txt

chemistryofaziri00clourich_Page_039.txt

chemistryofaziri00clourich_Page_002.txt

chemistryofaziri00clourich_Page_037.txt

chemistryofaziri00clourich_Page_023.txt

chemistryofaziri00clourich_Page_099.txt

chemistryofaziri00clourich_Page_121.txt

chemistryofaziri00clourich_Page_124.txt

chemistryofaziri00clourich_Page_114.txt

chemistryofaziri00clourich_Page_117.txt

chemistryofaziri00clourich_Page_127.txt

chemistryofaziri00clourich_Page_053.txt

chemistryofaziri00clourich_Page_019.txt

chemistryofaziri00clourich_Page_122.txt

chemistryofaziri00clourich_Page_020.txt

chemistryofaziri00clourich_Page_051.txt

chemistryofaziri00clourich_Page_060.txt

chemistryofaziri00clourich_Page_004.txt

chemistryofaziri00clourich_Page_123.txt

chemistryofaziri00clourich_Page_094.txt

chemistryofaziri00clourich_Page_104.txt

chemistryofaziri00clourich_Page_093.txt

chemistryofaziri00clourich_Page_071.txt

chemistryofaziri00clourich_Page_064.txt

chemistryofaziri00clourich_Page_092.txt

chemistryofaziri00clourich_Page_024.txt

chemistryofaziri00clourich_Page_100.txt

chemistryofaziri00clourich_Page_035.txt

chemistryofaziri00clourich_Page_001.txt

chemistryofaziri00clourich_Page_111.txt

chemistryofaziri00clourich_Page_059.txt

chemistryofaziri00clourich_Page_058.txt

chemistryofaziri00clourich_Page_086.txt

chemistryofaziri00clourich_Page_056.txt

chemistryofaziri00clourich_Page_011.txt

chemistryofaziri00clourich_Page_006.txt

chemistryofaziri00clourich_Page_112.txt

chemistryofaziri00clourich_Page_067.txt

chemistryofaziri00clourich_Page_128.txt

chemistryofaziri00clourich_Page_088.txt

chemistryofaziri00clourich_Page_062.txt

chemistryofaziri00clourich_Page_016.txt

chemistryofaziri00clourich_pdf.txt

chemistryofaziri00clourich_Page_085.txt

chemistryofaziri00clourich_Page_082.txt

chemistryofaziri00clourich_Page_018.txt

chemistryofaziri00clourich_Page_066.txt

chemistryofaziri00clourich_Page_115.txt

chemistryofaziri00clourich_Page_065.txt

chemistryofaziri00clourich_Page_077.txt

chemistryofaziri00clourich_Page_047.txt

chemistryofaziri00clourich_Page_052.txt

chemistryofaziri00clourich_Page_070.txt

chemistryofaziri00clourich_Page_032.txt

chemistryofaziri00clourich_Page_033.txt

chemistryofaziri00clourich_Page_103.txt


Full Text









CHEMISTRY OF AZIRIDINES














'i
STL RT C:H\Ni'.tIP (_1UiLi-H

















S I -1. ii .i i i i' i ,li. IL t
1N F .FT..i rFi[ it. LM t;,' i O i.L F ,_ ..-i.- i. r- FlOP THEF
r.rrF ., .F.r r,-.. T' .:.F F ,.:... rn


LrNi\VRSiTY Of fl.ORIDA

196)


































Tc. M. L.















The auchur Vishei '. express hii tninki to Dr. JJlCs [ Dyrup

lor Eukesting chis problem His kind crLtCcsrma nd i d/ice and hi,

boundless cntl'usijEwm nd encourjircr dTjurLnf the i curse of chLti cTrk

ire greatly d ipjreci.ted.

Thc author would ajso like cc thuak th-e i -culc S.[f, and iiiuv

briduJte itudencs s f the LTrni.racys ui fluriti fr ikini htI sc y in

Ci inesvillc ; cc merely n educj cl-.nul experince ['Lt an E;tre.rcl i n ,,'-

able one.

rinn;ci support by lthe 1l1cion-1 Aeroni.cLcs rn-Id p3tcu .dmi.,icC:A-

Licn (1q65-19'.b Cl.i Crid-jite school l of nte Leniversity Ot Flor!.u! (ilo.-

lIcb9 .* an.d the 14aci or,, : I tc.c- F.-jandatL.-n (196b ) is r'tL.. ully ct'.n.-l; .c .









TABLE OF CONTENTS


ParJe HL.

ACJJOWEDGMENTS .. . . . . . . . . LLI

LIST OF TABLES . . . . . . . . .... x i

ABST ACT . . . . . . . . . . . . xill

TRODCIIO . . . . . . . . . . . 1

CHAP ER I . . . . . . . . . . . . .

REARRAJGEMIENTS OF .2-AZIRLDLUECI.P.3XYLIC

ACD HYDRAZLDES . . . .. . . .. . . . 6

CHAPTErt I . . . . . . . . . . . . 20

FOP JW.TIW.I AiD PL\CTIVITY OF l-t-BLMTYEL--CHLORO-2-

AZETIDENCi'tl . . . . . . . . . . . 20

Formation tof -Chloro-2-A2ecidinones . . . .. 20

Easic Hydrolysi of -Ha c.~-AZetdliones . . . l

CHAPTER III . . . . . . . . . . . . 50

PYROLbIVI OF TRIPHElYLUMTHYr I-l-BUfM-2-

AZ IRIDUtlC'APFbOXYLATE .................. 50

CHAPITR IV . . . . . . . . . . . . 58

EXPER[MENTAL . . . . . . . . . . . 58

2,3.-Dibrcnobucyric Acid . . . . . . . . 59

2,}-Ditrcmobucyryl Chloride . . . . . . .. 59

Methyl ?,5-tDbromobury' are . . . . . . . 59

Methyl l-c-Buryl---Azizidtnecarbuxylate (51 . 60

Methyl l-2en-/l-l-AztrLdinecarboxylate . . 60

Methyl l-thenyl-2-A:iridinecarbaylare . . 60






CHAPIER IV (conc'd.) P;e !;..,

EXPERIMENTAL (con'd.)

He hyl C ls- l-c-BuLyl---He rhyl-2-. ziridine-

carboxylda e (t 5i . . . . . . . . . 1

Methyl Trns- l-L-Bucyl-,-lechyl-2-Azit idine-

carboxylace (.j . . . . . . . . .. 2

Rea;cion ui l-t-Bucyl-2-ALriLdinecarbcxylaci (li

With llydrzine Hydrace in Etrancl . . . .. 62

l-L-Butyl-2-Aziridinecjrboxvyllc Acil Hydrazlde (j . .

I-Bencyl-2-,.zirldinecarbic.ylic Acid Hydrazide .) .. .

I-Phenyl-2-..zirlidinec3arb..xyli Acia h,drazide () . o

I-Benzyl-2-A:iridinecarbc.xylic Acid Hydrazide-

Acetone H,dr3z.ne (15j ........ .... ... . 6

I-Phenyl-2-nlridinecarboxylIc Acid Hydrazide-

Acetone Hylrazc-ne (l:.)i . . . . . . . .. .

Reaction oi I[--Eucyl-2-Azzridinecarboxylic Acid

Hydrazlde sQ Uich Wuter . ... . . . 65

35--BucylaminopropiLnic Acid C(j . . . . .. ..

Thermal Deccmpoaition of -c-Butyl-2-Aziridine-

carDoxylic Acid Hydraziae (9) . . . ... . Do

Fragmcntaclon Lf I-c-Bucyl-2-Aziridinecarboxsyic

Acid Hydrazjie (91 in rh. Presence of Ai:benzene .. 67

Thermal Deccmpositltn of l-Ecnzyl-2-A:zridine-

carbc.xylic Acid Hydrazide () In dater .... .. 67

7.-Benzylaminopropl onic id ( . . . . . . 68

Thermal Decompcsiti.in of 1-Benz) -2-AziridLne-

carboxylic Acid nydrazide (_j) in Mecdanil . . .. 68

Hethyl )-Eenzyl3minoprc.pionace 11S . . . . . 69

v






Pace 1J.

CHAPTER IV (ccnL'd.i

EXrPRIHEIIL L (c-ntC'.)

Fragrent ctcn o' I-Benzyl-2-an'zlrldnee.bcxyl ic Acid

Hydrj..Ld (L-) In cthe re nerce c f :Cberi:ne . b9

5-Anilinc-prcpionic 'cid lHydr3ztde ( . . ...... .... 70

-Diphenyla irid ne . . . . . . . . 70

I -c-Butyl-2-A lr ldri ecar in l ('.) . . . . . . 70

Ethyl B n :yl rin c c . . . . . . . . 70

Benzyl iinci L ic Acid Hydr3 tde (.) . . . . . 11

AnlllirocJie ic Acid Hydrzilde .. . . . . 71

1 ,-Diphenylalrl Ilne ,(j-tc bi hliLy LC

Hydriz i ne liydraev ................... 72

1-L-Bucsl- -.ai .ridine 3arl in.u (C 'i -S abil cy

to Hlydrzin.: Hydrac.. ..... . . . . . 7

BenLyla.inurniccic Acid Hydri-ide (:.)-Stbiltlcy

to Methmcnol . . . . . . . .. . . 7-.

AnIllLno.ceic ncid Hydra:ide (\j-&tabllliy

to Methanol . . . . . . .. .. . 75

Ethyl I, .-Iecr mecchyl-. eneglycid ce . . . . . ... 7.

.^-Trcramcerh lini-4--Hfd *-.xy-5-Pyr.. lidc-nc . . ... 71.

SodiLu and Lithiun, -c-Bu[yll-:-.leiridice-

carboxylrace ( and 4 ) . . . . .. .... 74

Sodium C_- 1-c-Buyvl 5-Hthyl- -Az irdine-

carboxylace LD . . . . . . . . . 75

Sodiu Tr nr-l--L-e-Lc il--,lerhyl- -

A-irldinecarbo.xylu e C(j. . . . . . . 75







CIR PEr IV ccinE'd.l

F.XPRLrMENTALL (coot'd.)

Triphen lIetrh l 1"- -butL,-I-.-.,zirldine,? rboxyl te (i j . 75

Pyrol.,5is c Triphenylrir[tyl I-L-Buryl--

AzlridinecarboxylJa ( .1 in b n:Ene . . . . .

Thcrminl Decomipositnlc n of Triphenylmichyl

I-t-Butyl --..Tirlidlrne rbxylhr e I91 ir Cumene . . 7

Pyro.lyiis cf Iriphnylmr thl 1-c-Butyl-c-

AzirldinecArbjxy lat (91L in Ben:en. In

the Prc.ence of L-ButanLi . . . . . . .

Thermal SE bility ci I-[-K ur;1-2-

Tr riprinylrc Lh" la: irl.me ( . . . . . . .3

Pyroly t of Trtrphenylrt-ictt l-t-bS yl-e-

A.zirfdinecarbo:iJ l.~J ~ (L:I) in herr.nol . . . . i9

flt'rhIl IrIphenylmi hyl Ether . . . . . ... .

?e.crion of Lirh:urn 1-t-Butyl--.-A:.iridine-

carboxyltic (L2) uith Tht;nyL ChlcriLd . . . ... . '

F.ection of S,,dtur I---But;l-2-4iridine-

carboxyls te ( :) icth ux1ll Chlcride . . . ... 81

Re.ct ion ou Sodium 1-t-burt.'l-''-AztridrinccarbozylatE

('i with Cxalyl Chloride in the Presence of

irietrhyLs mine . . . . . . . . .. .. . 81

REaction cif Coium Cia-1-t-Burvy- i-Ictlrh-,-2-

Ariridinecarbr.,:ylate ( ) uich O: alyl ChlorJd-. .. .. 81

Re3ccion oi ccdiium TranJ-i-t--Buryl-'.-ilechyl-'-

AztriJdiLuerhboxyltea (' .S i at. rn xalyl Chloride ..... 8









CIsPTLER IU (ccin'd.)

EXPL.RIllM H..L (ccri'd.)

.inr.' Lxpjn.Lon of -odiLn l-t-Ejutl-2-nz!ridine-

.arbcA/;la e (51) -1 th [iC.yl Chlcrlde in

e tri le . . . . . . . . . j

Rini ExpansLen cf _odium C.1-|1-i-Butyl -'-1 thy'-2-

zILritdne..irbboxyaI e -j) with Nosyl Chlor.d-

In Acc onitrl le. . . . . . . . 8.

Reacltrn cr [ .-.. m .i. -=l-t-ejt,l-;-Mrth:l- --

,AzridiQccaLbo^A) te (-' icth .osyl Cilrtide . rd

C iL t -Bu. ,I 1 .-Me t n1 l- 2-A =i r idi n -

Carb. ).li.c nh dride Q ) . . . . . . I

RecCact in cf i -l -t-Bucyl- .- heth:'l-42-4ir Iline-

LdJ6I6 :XI ..riy~ ri.Js Q^; .'. :r:nii4,is

MeLhcxld: in Mlthnor.l in the Prcesnce or

Nonyl Chlrri d . . . . . .

K action of 3cdiu. Trr ,-l-t-3ucyl-5.-MCthyl--"

Az rl idir ,carbox.ylart 1, 1 p icr. t No. yl Chlcrid 85

tNmr .i the An'OydrJdei in iulir DicKlde . . . .

NI..r Spectra f .!-Chlorc-2-.-:erd nc.nes in

.,incmory Pentai lu.r lde-;ul ir llr.'ljde .... ... .. 87

REducctrn el -c-iPur.yl-'-Chl:ro-.-.ze[i-

din,-,i (._I) with Zic . . .. . .. .. . .. 8

I-t--Sut, l---Az ;l lrr ne (51t) . . . . . . ES

Fearclor cfL l-r-Butyl-5-Chlrc'-Z-A-e.c Idinone

(j_ vwich Eodium h)droxide . . ... . .... 88





Pa3 e No.

CRtAPrEl iV (c.nt'd.)

EXPFRINEIJLAL (cont'd.i


P.eactiln of l-t-BuyI-5,-CIlorc.--izetidznc.ne (JfIi

wvih Ldiunm tLitho. ide .. .. . .. 89

Reaction ci CI-U-c-Fl.uc l-'-Chloro-14-leethIl--

Azetidir, ne (~9) i-' h Sodium Hydroxide . . . 9

Reaction oi Trnns-l-t-Burtil-3-Chlor&-',-l ihyl-l-

i'-etidincne ( '0i "ith SodiJin iydri-t.ide . . . 90


SPLCTL.A

C-?rmpound Sol vent

1 lethyl Cis---t-butyl-'.-Hetnyl--

A:ir[dinecrbtxvyl3ce ( CC .......

S .lethiyl Tran3---t-Buc. l- .-ilechyl-_-

Azicidinrccrbux late (rI LCl4 . . .

i Sodium C I-l-c-E.uyl-- -let li'---

Aziiidinccarboxlate (Qj) D0O ... . 9'

4 Sodium Trar.s- -t-Buc,'l-5-Ile hy l-

--Aezlrdinecarboxyla e (.e) D' . . .

5 I-L-Butyl-i-.'ziridlnrcarboxyLic

Acid lHydrsZide (9I DI' ...... 9j

t 1-Benz l---hzr Ldlnec3rbox''lic

Acid Hydra:ide l(j C :D1, . . 9

7 l-Penyl-c-.'A:ridirecarb'-x:ylic

rci d IHydr :ide (J ) CDCl, . . .. 9









F;PEC r (cont'd.i

C.:.rmpcund

8 1-Ben-:yl---P=lridlnecarbxyIllc

Acid HyJraz de-A.cecone

hydrarc.ne (I '

9 I-Phenyl-s-Aziridinecarbaxyl.:

Acid Hyvra-zide-AceC ne

Hy.dra:cna Jl

10 Trirhcnyl.-ethyl 1-i-1ucyl-2-

Azirlcln ec? arbD.:v,'laLe (l

11 l-t-Bucyl-'2-Ir pFhenylc, ethyl-

SziritLne (, i

12 l-r-Butyl- -,Chl.rc-2-

AetidLionne I'j )

1 E 1-c-Butyl 3-Ch I orc-'-

A=e d i.nnre ( 0)

t1 1-ct-Butyl-By-C hloro-2-

A -ecidin-ne (50)

15 Cis-1-t-Butyl-3-ChICrl-l-

Methyl-2'-AzetidinunE l .

16 Clsl--t-But.,'|-i-'nliro-4-

Methyl-?-A.ertidinone (c 9)

17 if l I -1-t-Bu I .-CI lor ':-4-

Hethyl-2-A-zeLddinone (c.9

18 TrIns- I--Eutyl-.-Chlorn-'.-

MHehyl-2-.-':etldtnone ( )


. . . 101


SbF 5S


. . . . 101








. . . . 105


rjPe Hf,.


Sc lvcnt


C DC I



CDC I




Cli 14



CCII.


. . . . 99


EbF 5*SO,



CCI





Pj.e I a.


SFECTP.x


Comp. und

19 1-t-Butyl-.-:X ridiJhnce (5(.

E2 1- L-Butvl-2-A-zir J incc re ?-.' :I ic

Anhydride _)

21 Ci;-l-t-Buryl- ,-ftthl-2-

Aziridinec3rbo'ylic

Anhydride ij'

22 Cis-1-L-Butyl-'-riethvl-1-

Azsbicycl. [ 1.1.0.] Pucrnc-

2-One C3tion (j

2) Tr'ns-1-c-L,-I. -,--flethyl-L-

Azlrldin.-c i -s ./ ic

Anhydridc C20.

24 Trans-l- -Burll-4-fIrh. '1-1-

Azabic/clo. [1.1.o.] Rutane-

2-One Cjr ion (5)



BIKGPJ.FrHliCsL JlCH ......


Solcenc

CCI,




LC14





LCI4


. . 107






1)7


SO,

.












LIST I'F Ir LE


Table .'No. P.e p 'O.


I Rinng train [lerranlncd Fr.m ileat! oI

Com us n . . . . . . . .

II Vicinal Coupling, Contants ui l Ailriin

and Azetidinrne Lne Prtcr,. .... .. 5

III Pin,; Strain in ihr -tlcrmb-: rd Pin . . . . 28

IV Che.ical ihiica (51 in ,li'r Dioxide

Relativ, to Eurern3l TeLr.amethylsilIrne

In Carbon Iecrachloride . . . 2

V (nemjical s.[irt (5; in .ultur Di,:Ade

Relative to Y.ternai IIe ra.,ethylsilene

in Carbcn tetrachl ride . . . . .

VI Chanicil -.hifcr (i) Rilative to EKterrnl

Tetramechylailnec- in Carbon Tetracrhluorid . . 0

VII .pparent ',E ccnd GOrdr Rate Constants for

Hvdrolyaia (0'.5 I N a(H.865' ELnmnol, 5rl . . 5







Abstract oi Dissertation Presented to the Graduate Council
In Partial Fulfillment of the requirements for the Degree of
Doctcr of Philosophy



ChE.~STRY OF AZIRIDINES


By

Stuart Chandler Clough

August, 1969


Chairman: James A. Deyrup
Major Department: Chemistry


The unusual reactivity of some 2-aziridinecarboxylic acid deriva-

tives has been investigated. In the course of this study several 1-sub-

stlcuted-2-aziridinecarbc.oylic acid hydrazldes uere prepared. The

fragmentation of these hydraniJes was stuJied and found to proceed iuth

formation of dilmlde and ketene intermediates. The mechanistic implica-

tions cE these results are discussed.

The reaction of sodium l--bucyl-2-azirldinecarboxylates with

thionyl chloride, oxalyl chloride, and arylsulonyl chloride uwas found

to give good yields of 1-r-butyl-3-chloro-2-azetiaLnones. Stereachemlcal

e:.dence and product studies suggest the Intermediacy of a l-azablcyclo-

[1.l.0.] butane-2-one cation In the ring expansion. This is confirmed by

nor studies of 2-aziridinecarboxylic anhydrides in sulfur dioxide. The

synthetic utility of this ring expansion is discussed.

The pyrolysis of triphenylmerhyl 1-E-butyl-2-axzridinecarboxylate

was investigated as a possible route to a 2-azirine. The pyrolysis did


xili







noc generate the 2-aztrlne, but Instead 1-c-bucyl-2-Erlphenylmechyl-

aztridine and IN--buryl-triphenylmeLhylmeLhylamlne. The mechanism of

this reaction is discussed.


xiv












INTRODUCTION


The ultimate goal of the physical organic chemist ta the complete

understanding of the chemical and physical phenomena associated with all

organic matter. The unattainability of this goal forces the chemist to

attempt the understanding ot simple systems whece, by theory and experi-

ment, the IronLters of knowledge can systematically, albeit slowly, be

extended. In Lhis manner the concepts of radicals, Leas, transition

states, molecular oroitals, and the three-dLaensional structure of mole-

cules have been born. Reaction mechanisms for maiy reactions ace now

understood (or at least thought to be understood), and the effecc of

additional subscituent groups on reaction rates in various byLtems can

quantiLatively be predicted utch reasonable success.

it has been shoii that the presence of an unshared pair of electrons

situated close to a reaction center in a molt;ule can enormously aCfEct

the rate, direction, and stereochemistry of the reaction. This propinquity

effect, neighboring group participation, Ls quite dependent on the geometry

of the substrate.

Another ohenomenoii known to dramatically affect the rate and direction

of a reaction is ring strain. This is the extra free energy in a cyclic

system Which can be correlated with the unusual geometry of the molecular

orbital of small ring compounds. The concept of ring strain, first pos-

tulated by Adolph von Baeyer in 1835, has attracted considerable interest

and undergone extensive refinement. The effects of ring strain are most





2

apparent in ring closure and ring cleavage reactions, and they decrease ulth

increasing ring size as one might expect. Generally heterocyclic rings are

not quite as scraLned is their analogous carbocyclic rings.



TABLE I


Ring StraLn DEtermined From Haeat of CombuationAc


Conound Strain(kcal/ mol) Compound Strain(kcal/mol)

Cyclopropane 27.6 Thiecane 19.8

Thilirne 19.6 Cyclopentane 6.5

Oxtrane 26.6 Tetrahydrochiophene 3.4

Aziridine 25.0 Tetrahydrofuran 4.6

CyclobuLcne 26.0 Pyrrolldine 5.5

Dxe.ane 26.4 Cyc lohexane 0



The possible reactivity associated with small strained rLngs coupled

with the possibility of neighboring group participation has stimulated a

program of research in thLs laboratory involving small ring heterocyclic

compounds. The research presented here explores the chemistry of some

2-aslridLnecarboxylic acid derivatives ti an eiort to understand the

-eMchanisms of the rearrangements which are found to occur Ln these systems.

The field of azirLdlne chemistry is not cau. The first aziridine to be

formed uas the parent compound, echylaneimine, synthesized by Gabriel

(1883) only three years after Baeyer posculaced the Baeyer csrain theory.

The correct structure was not assigned until 1900. Since that ime a

-..rge number oi routes to the astridine system have been discovered, a wide

variety of substrLr.tu groups has been attached to the ring at all three

petitions, and the chedlstry of many of these compounds has been explored.







The work done to dte in this ind other laboratortes indicates chat tne

electron pair on nitr.ien sL capable of particip.cing in reacLion: boch

on and near ch? ring. King scr.in al.o seems to play a ajor role in the

chemistry i.f this system, and ring clejvade Is trccuently observed

Three classes Ct 2-~zrtrlIdnecurboxylic acid dJrivrtives are dis-

c.sed ir. this *lrserrmEton: 2i-airidinecarbuoxylc aciJ lydre:l3es,

L2-airidilec3rbcoxylic acid sits, and tripheri.mei yl 1l-c-butyl-;-a;trndine-

carboxultce. The chemlitry or these compound will te discussed separa3ely

in Chapters 1, II, and III respectively.

The s)ntheses of all or these cr.mppunds baorn sbih the syntheses cf

t[h appropriate methyl '--zirndinecarboxyyltes. Theie tsters were prepared

usinc ptdri.cdAes patterned irter those it the literature by croatini the

appropriate rethyl 2, -diurumoipropicn.te vith triethyl mine ioHlo..'d h) th

ippropri le prinmir amine. Thc.e reactLcns 6 .ve rALher goJ yi.:la; or the

.ziridine s:cers.


0
I) E13t Ro-t. IOCH
RCHBrCHBErCO2CH3 ) J 7
2) R'NH2 1
R






In th'; firrniIrain of rechyl 1- -butyl---methyl-2-astr dincrarboxyl te

two isomeis Lt re obtained. It uWi found that the choice or soalenc deter-

mined uhich ijoier predirainatd In the project mlixcure. When Ene reacci n

was run in i.tchanal Laie r-tio of cia to tcriq azridlne W;s -boct four tc

cne. Uhen excess t-butylamorn wu3 used 3s the iolvent, the rotic of cts

to trans :iridine w-s about three cc five. SLmilar solvent effects hjve








been observed before in CatLriel-tcype aziridtnE snrn, c.-es and it Las con-

sidered Irturnate chat Lhij effect occurred here a ict facliLt.ted sepira-

Lion of the iiomi er The Ci t isoner -a.e obclrned In a pure staL'. by

spinning band distillation cf a mtixure c.f the ci and tr ins i3.me-r. The

trans isomer was c cpletely separac d iron che cis in the asi e rinner, al-

thouh at firsc it ajc not sc a=r ced irc.' ..a r1ajcr LI p rity belic'vcd to be

ruehyl r-oiautlaminr ioccace. Trre impurity did not interfEre ilr subhse.uent

re=cclu.i- huever. A r esor, oble mecha.Lsm for iLEt formactiLcn *o'd I:V'olve

acid ca~alyzed hydrcly'.i of the i.,-dipale a sahoun bilou.



0

O" CH3 O A CH3 H urhChc2C
S 0 H 2
T-Bu I-Bj






Later it vis f und that if the crude atrirdine ester uas dissol\ed In benzene

and uishl-ed Lth aqueou icOdLum c3rbLcnate prior co the di.tilllticn, this

difficulty did nor arise, and the trans ester was obtained janlyticall.

pure.

Thc 5as=sgnT.enr ot fLEreochemi Tary to the aziridines and aearidrnones

to be discussed in Chapter II uere m.de on the basis oL coupling consE=nts

obervec; in their nnir spectra It has previously been shown chac the

vicinal couplln- aonstants for procLns Ct t o each other or. thc aziridine




Refer o Chapter III for a related h'drolsis of an -.iridine 1,;I.-dip le.
For in a naloccus acid catalyzed deccmpolstLon, see Reference lu.







ring range betr en 5 .arn 8 Hz, but ior proroin rr-ns t.- each corner tne

couplir.c cor,?r.ars jrop to becteer 2 and 5 Hz. .Simillirly cis cc-.pLn1g

cun3tints .ar larger th.n trrn3 coupling con c~ntr in the izetidinane ring

In accord u-lr, che Kirplus e.-ujcica.r. n aljsis Oi the nir speccj oi tr.e

a:zridines and azetiainones prepared in this work uve. the iolloitn vJlue3

for cne vicinal coupling consucnti (L'.L~LE 1il TFhe c 1 ster- -chemiscry ujs

absignrie c the onmer hI.'in& the cre.ter vaLue.


TAELE II


Vicinal Couulln& ConstJncs oa ArrldLne and AzetidnL e Pri .Lr. Protcr,


Co unJ (Ht; J OCn)
Ctmicund ls crsns


0
CH3 ,OCH3 ., 2.4


I-Bj





CI O 5.1 1.7


CH3 IBu




.I C' 5.0 2.1



I.Bu














CHAPTER I


REARRANGEMENTS OF 2-AZIPIDLUECARBOX/LIC
ACID HYDPAZIDE.S


The generation of carbenold (' 4 and primary carbontum ion Q)

centers on a carbon atom adjacent to the 3zirLdine ring was the original

goal oi this work. The reactiviLv of these intermEdiates should yield

considerable insight into the neighborLne group effect of the aziridine

ring. One synthetic route chosen for generating these species was the

thermal decouiosition of the L sylhydrazoncs (.) (Bamiord-Stevens Fe-

act on) cf appropriate aziridlnecarboxaldehvdes. 15 The proposed syn-


RH

R


NNH Ts



R


3


H
--H

R


2


thetic route fc.r formation of

after Roberts' synthesis of

McFayden-Stevens reaction.17


the aziridLnecarboxaldehydes was pa~cerned

cyclopropanecarboxajdehde e () using the







0
SOC2 H 2rIH 21120
OC H


0



4


0

SI- fJNHNH2


ITsC

0
e T PJ H NHTs


16%


This route resulie in failure at the fire srep Wh ni methil

l-t-butyl---aziridinecarbcA-lace (!) was treated wich hydrazine hydrice

according tc. nr~ial procedure~ for Che gnerjticn oi -.arboAylic acid hy-

dra3LJdca, the unly product imoljtej uas j.-c-t-buyiamnnopropLcnic acid

hydraziei J i (65'.).


s-7 OCH3
1I
1 Bu


H2lNH2 H20 I-BuNHH2CH2 C HC-NHNrH

6


After thit wc-rk was completed, Professor R. Hulsaen poinLed ouc chat. he

had observed a tsmilar reacticn ith rechyl I-phenyl--2-azrldirnecarboxylate

j) and hydraztne hydrate.


0
7 OCH3 H2NNH2 H20

C6H5


C6H f5rHCH C2 CHOIOHNH2








The only comment aude by Huisgen concerning the mechanism of the reaction

was as follows: "Fur diesc interessanre Hydrogenolyse des AzLrLdinringea
19
1st uns keLne Analogte beksnnc. 19 Since the proposed route to the

azlridinecarboxaldehyde was no longer promising and since the reductive

ring ecission uas neither expected nor readily explained mechanLstically,

an investigation of the mechanic oG the decompLsitLon of the aziridlne-

carboxylic acid hydramides was begun.

When a slight excess of meEhyl I-c-butyl-2-sziridinecarboxylace (5)

uas stirred at room cemperaEure for 9.5 hours with hydrazine hydrate,

analysts of the resulting solution (in 0tCJ0) by nmr spectroscopy revealed

formanion of MeLhanol and a slight change in the paccern and chemical

shift of the characteristic three-proton aziridine ring multiple. Al-

though its instability precluded isolatcin, the new compound was assigned

the structure of l-t-bucyl-'-actrldznecarbcxylic acid hydrazide U).

0 0
7/- OCH3 H2NrjH2 H20 NHNH2


r-Bu I-Bu


5 9


When crude hydracide 9 was left at room temperature for four days,

considerable gas evolution uas observed, snd a solid identified as

1,2-di-;-t-butylamnopoprpionyl hydrazine (101 precipitated. ReflLuing

the hydrazlde 9 in wacer produced ;-t-bucylaminopropionic acid (11) as

the only recoverable material.












[t-BuNHCH2CH2CONH-]2


o 10

7N 7AMNHNHI2 \

f-Bu

9 ,0



i. BuN HCH2 CH2 CO2 H









Because I-t-butyl-2-aziridinecarboxylic acid hydrszide (9) was so

unstable, other aalrtdine hydrazLdes were Eought In the hope that they

might be isulable and thus more amenable to study. The reactions of

methyl 1-benzyl- and l-phenyl-2-aziridinecarboxylates ( e and 7 wiLh

hydrazine hydrate give spectrally pure crystalline compounds identified

as 1-benzyl- and i-phenyl-2-aziridinecarbo ylic acid hydrazides (. and

14) respectively. These solids themselves were not very sacble buc could

be kept under nitrogen in the refrigerator ior extended periods of time.

When dissolved in acetone they formed the corresponding acetone hydra-

roees (I5 and 16). The hydrazones are stable crystalllle compounds for

which satisfactory elem enal analyses were obtained.








0
7' OCH3 H2N IH2 H0
N
CH2C6,5,
12


0
N7 OCH3 H2NNH2*H20

C7H

7


0 0
NHANH2 -

CH2C6 H5
13


0
A2 NHIN H2

6 5


0
-7~T
N
CH2 C65
15


0 0


6C5


AlchLusrh isoljble, the h:bdra;:tls _L ind 14 behaed sir.l.irly ct
l--bturtyl--alir ldinecarb x.,yl i c id hydraztde t,'i. The tc-nz:,l hydr.-

zlJe (L) gave 3-br.zyl minaopropLtn'-c acid (L) 'hen ref luxed Lu wader
and m tthyl '-ber. ylninopropion re (1_1 identify ed as it. hydroc hlorde

(J4 -hei' ref luxed in mer hdnol. The phenyl hydraztde (lt ', 'hen re-
fluxed -ich excess hydrnzine h:dr.re in ethajnl, ring cnered co form -

mnillnopr.pinic: cid hydrazide ()).


0HNH H20

CH2CGH5
^CH


C6H5CH2N HCH2CH2C02H


H HI0 H

C6H5CH2 NHCHHC2CH2C02CH3- [C H CH H 2CH CH2 C H 2CH ] CI'

18 Is9











0

NHNH2 H2NM H2H20 0 C6H5NHCH2CH2CONHNH2




14






Numerous mechanisms can be formulated which are capable of explain-

Ing the observed products. The first to be considered is a direct re-

duction of the aziridine ring b./ either hydrazine or perhaps dilmide

derived from hydrazine. The intermediacy of diimide has been uell

established In reductions involving hydrazine. The reduction of s.m-

metrical double bonds proceeds smoothly vnd stereospecifically to give

cis addition of hydrogen. The reaction is thought to be corcerred, in-

volving a sLx-membered cyclic Lransition scare 0).20








N Nx ,


20






* Prior ,xcdEtion of hydrazine, possibly by air, would be necessary.







In an an3lcgous runner concerted reduction ot the azirldine ring was alsc

conceivable. Driving forces for the reduction would be relief ot ring

strain and iorlatilon of nitrogen. However, 1,2-dlphenylvaziridce ( )

and l-t-butil-.2-iziridnecarblnl i.; were Jcable to nyvr.:cne hydrae

under the reaction ccndlcins


CH
N' 65 H2NNHq H20
N3O REACTION
C6H5
2I





7"" 0 H H2NNHZ H20
N --- NO REACTION
I-Bu
22



This res ul combined with .he uoseivatLon chat azirldine h~iraziaes wer-

Isolared anJ then jlloued ca ring open rules out the possibility c-f

direct ring scissin by hydru ine.

rhe role the azicidine ring plays in tch reaction also deserves in-

vestigdation. h-'e ubservltiUns thjL benaylamino- and anlltnuacetic acid

hydracides ( and Ti are sctble to the rectcin condlrcons Implies that

the reactivity observed is ntc to be associated with C-ammno jcid hydri-

zidls buL indeed Is in some uwy associated vwih the azlrLdine ring. IL

is pertinent cco that cvcloprcpanecarboxylic acid hydraj:ie, the carbc-

,yclic analog, is a stable compound, apparently ncL enjoyin, this

reactivity.16

CH3OH
C6H NHCH2 CONHNh'H2 C- O NO REACTION
65 2 2 a







CH3 OH
C6H5 CH2tiCH2CONHNH2 C--H3H ) REACTION

23


Careful inspccticn of the above dati suggested :hat. lie j:lridlne

hydrazide rearrangerent might invo .le rtitcjioun of dllmjid and an amino-

ketene intermeditae. nie aminokecene intermediate (e nicely accounts

for all of the amiLnu acid dervattves observed ai prc-ductc or the re-
21
arran cmenr.

HX
RrlHCH2CH=C=0 --- RNHCH2CH2COX

25


Formcaion of dilmide accolnr.s for ch, c.opous gas evolution Dbser.ed.

Dilmide i, an extreiely unscjble compound alrhou.h it does ha~c a iirite

liEetime as is evidenced by itr IsE.lation at loi, c=mpracture iolIc'-d

by decorposi rio, rn uwarmln,;.22 T o parhw.iys arE vail=ble L'ir thermal

decompc.sgiLin, boih of which yield gaseous product.: PeducCln oi j

second mcle Io dilmide E. f rm hydraziie and nicrogen smEis cE be f'.'ored

over spontaneous decc-ipcstEcio*r tinr hydrogen and nirc-n, I.'


2 HN=NH -- H NNH2 + N2


H N= H ----- H2 + N2


Ccnfirnurory evidence for the presence of dilmide as in iact

obtained by observing concomicant reduction of azubenzicne (2j) C hydra-

zoben:en-- C27) during the convereJson of l-bEnzyl-.-azLrldinecarbo,\ lic

acid hydrazide (1U) tc methyl 3-benrylaninopropir. ce (tjL) as well js in

the conversion of l-butyl--azlri.dinrcarboxylic acid hydrazide (C) to

3-c-butylaminoprpionic acid (.Ji.








0
AIrJHINH2 CH3OH

*I + 0r: C6H5CH2CNHCH2CH2CO2CH3 + 0frHnH0
CHZCH' 26 IB 27
13



0
Silj H CH30H
-H H2 C TBul JHCHCCrlGCO, H + lJNHNHJ
IB + rj H20
1 Bu


The frjmr eiation of ,-A-ubaticuted carbozylic acLd hydrazides to

kereres jnd diimrde r.as been observed b tcre. for cx'nple, Pa,..lscn nd

Scove' rave studitd [ne tragmentalion o"i .-mesyl hytra.ede it and observed

ihe fcrnwritn oi a keterne at the rcilat'.ely low temperature cf 5)i.


A 0
0


28


0
V HNIIH
- 0M -


Buyle has 5sudieJ the base cacalyzed fragmenctaion of mino-, dl-, and trt-

chLoracetic actd hydraztde hydrochlorides (.) These cuo apparently




* The temperatures generally required to pyrolyze.klkyl and aryl carboxyllc
acid hvdradides ore on Llit order of 151j-175 .







undergo a Grab cype fragmentcilor gnerating keter.as and dLimide.


0
CI-CR-C-NH-NH-H

29


-Cl R1
--- C=C=O -- HN-NH -- P
R'


there irc ronmber of Jeta lled patrs by -hicch i -- z ridlinec arbo At ll;

acid hydrlzide could fr.agentr to Efrm diLmide and jn airlnoketene (U).



0


R







R H- 25
Ftl


H2t1-JNH
C.

R


HN NH
)R Fi NHCH2--

30


A These tormulitions are not intended tE imply an/ necessarlly concerned
rlinng in the cventi leading from the hyirtzides to the products.






Mechanism C can renc3tL.'ely be ruled oat in vieu coi the kn on course of

intramolecular aztridine and epo.idE ring openings.2 Thois ore would

expect attack to occur at the !,-position and not at tle ?-position.

Als.:, based on what is knoun abcur the chemistry of Il,-dla:tecitnones,

tnh suggested inLerMueJijte (i j) should be Stable under the reaction con-

Jttions. The 5, .-dietsidlnnin thencazed to date are generally sub-

acituted at the 1- and 2-pCuotions. They do dciir-pise at etace-J [cm-

peraturs., bUt to iorl iaocyanites PL and Schif buse, (ib .



Ar Ar Ar ,Ar.
X -- + 11

R 0 R R C
R O

32



The ub Ervaton that the cleavace is iacllitatei by electron withdrawing

groupE 3t the 1- and 2-positiorns has been inter re tel as e'.deLcc tcr a

diradical interrediace Q(.,) formed by rupture ci the. eak i-li bond. -

Ar Ar.

R -4
R' 0
33


Since the postulated intermedijce diazetidinones (L)) no not have radical

sc.bilizing groups at either the I- or 2-position, Itc a expected chat

this type of cleavage would not readily occur. Cleavage to form diazo

and keLenc intermeditces has not been .bserted, and IL seems reasonable

thca chis aculd be an even higher energy process.







The data available are not sufficient to distinguish between the

first two mechanisms (A and B), both of which are Grob type fragmenta-

clons.'1 Although in non-hydrogen bonding solvents the hydrazides might

be expected to exist in an intramolecularlj hydrogen bonded confornacion

such that fragmenration would readily proceed according to mechanism A,

the solvents used here (i.e., water, methanol, ethanol) might seriously

affect the conformrtion assumed by the hydrazide. Because of this it Is

difficult to differentiate between the first wou mechanisms. It would

be possible to gain some insight via a kinetic investigation, but the

hydrazides were never purified enough to make such a kinetic Investiga-

tion feasible.

A perhaps more interesting problem arises when this reaction is

contrasted with the rearrangements of epoxy hydrazides. Harrynov and

Belova allowed epoxy eaters (4) co react with hydrazine and were un-

able to isolate the epoxy hydrsaLdes (5). Instead, they obtained

hydroxy pyrazolidones C('. The data which they presented ;a' not con-

sidered sufficient proof of structure for the pyra:olidones however.

Following their procedure, ethyl a, 6-cecramethyleneglycLdarc was heated

with hydrazine hydrate. Nmr and mas3 spectroscopy verify the pyrazali-

done acructure of the crystalline product. I e mechanism of this re-

arrangement presumably involves intramolecular nucleophilLc attacK ac the

3-position of the epoxide ring (route A). Initial attack of hydrazine at

the 5-position to open to a hydrazine intermediate (1j followed by ring
'2
(route B) closure to the pyrazolidone has also been suggested. The

question remains, why do epoxy and azirldinecarboxylic acid hydrarides

react so differently?











H
HN NH
R 0
R36

35

R OC2H5 2 H5R



S 34 -h 0 OH












H











T aN .
38 36OH
NHNH2

37


The aziridinecJrboXylic acid hydrizide decomposition also contrists

remarkably UiLh re irranisents Dof -irldLndie ind epauy hydra=one P..d*a28b

has shown that the cosylhydrazones cE epoy kEtones I(j rejrrange tG

form 4-hydroxy pyra:olines ( j, snd Cromweull et jl1. c hve shown LhaL

phenyl hydlrzones of iziridine ketones (Ii rearringe lto frm k-amino

pyrazollnEs 41) ThEej rejrrangemEnE& hjve been eyplalned by pos[ulat-

inl inLrjmolecular nucleophilic jttjck E Ehe '-position of the heterocycle.


H
TIII


R Ts 'N R


38 39 OH











0 NHq

R R
R


R NHR


40 41





Again, why does the aziridlnecarbo,/ilic acid nyidrazide fail to re-

arrange by intrarmolecui.r accack at the ;.-pc.ition cc. ficrrm an aiinopyra-

zclldone? rhe nature of the hcEterLacmn ((',tl) probaDol does not pla/ nhe

maJcjr rc.le in director. the ci.urse of the reacLions E lric both epcxi and

aziridine hydr.=zc-nes undergo 3rnAlC c.-us reirranerepnes. rine ansur pii-

Iably lies in steric and cc-nrc.m.rtii nal effecs which cc.ulI be rieatly

affected by substituent groups or. the ring and to a Icsrer cyccnO b,% Eit

heterratom and groups or, the hecre.racom. There Mia be a ianc-.tic tr.n-

gitnmeric effect facilitating iragur.entativn relati.'e C intrarmlecular re-

arrangement of the aZiridJnecarf-,.yl c acid hidr,-ides.)1

In any c-ae, it can be concluded here chat e-aziridinccarbuo:syic

acid hydrazides do fragmnt Lc, fIorm atrinokecener and diimlide one impor-

tant driving force is relief of ring strain. The reactic.. appears to be

general tor ariridines with vai iLu subsltiucnts c-n ritroier. (aryl and

alkyl). Tie reaction ayiv or may not find ayntblcic utiltry, but mechan-

isLlcally it d.es deserve further investiactc-n.

Another problem deserving further actentron is the original o;al ct

this work generaiec.n of carbenoid and primary carbonluar ion centers

adjacent to the aziridln? ring.














CHAPTER II


FORPi.itiOi lisiO ;,CIrVITY OF 1- -cul'i V-ChLiuRf--. -sLTlDIi:rt.T1


Forr. L.tur, of -CMhlorc----.,;etridnones

Tne ,--a:e~ idcncnr. rLng us first successfully s-nthealsed in l,57i

uwhn II. 5EcudIngcr observe that c:/cl zILon oci *ilphervyll'et'ne (4I) ind

bcr.,:ideryde ian l (j1 yielded I ,, ,,',-LeLtra. hen*.-l-3;azee ld none t4). ''





02C=C=0
42



0CH=rN
43 44




Since tn t tkine 2-azecidnoneni (?-lici3ms ) ha.'e j3EEcricd ccn'L.arible

interest =&a reactive strained hetcrocyclic ring system and aJ a Key

part ci biologically active .:eph.lo3prt n (i'| nd prnicillin (4)

structures. Eec-use of thei biological -ctivity Lf these system, a

varied, of routes have been developed rco generate the areridinone ring,

and a~m as3pecC of the chemlstr> of az.dtndinonri h3e been investigieed.

Mlst of the risearc' in this field bas been cirrled out since World '.'or

11 and includes the totl synchests ci penicillin '5













, RIIJH __c 0A


0 s ,C 2 ,OAc




45


P14N S



CO2H



46


This chipcer will deal wlch the discc.,,ry thit certain izlrildin de-

rivati.es undergo ring expasjlon cc. )-halo-2-ictZEtdnonres (Lji. Sce of

the reactions ch3aractersclc c~ this heterocyclic rini will also be dis-

cuszed.




CI O



I-Bu


47






This work b.gan when an attempt to aynchestie 2-.lrzirtnecarbc.nyl

chloride (.3) resulted in new path' coC the :-halo-2-azetidlnote syst~m.

When ilLhium 1-t-bucyl-2-aziridinecarboxylace (Lj wUas created uith thionyl

chloride in the presence of ex,:Ea sodium hydride, 3a ;' yield of I-c-

butrl-'-chlcro-2-a-ecidinc-e (5.) was obtained.












0

ci

0B

OL, 48



ut-Bu



50





Tn.: 6r.cturEr of the j ertdlninn (Qi3) ar sjilned o-n [te baais ci the
-L
nar spectrum, i crbctnyl 3bsc.rptlcn in the it at l7n0 cru (ch:r-crerlstic

of the -zec;dl[ncr rini),:" .Id a E.tisf icory eltmencjl jnl-si's Ihe

Lass speccrum, srowud parenL ic.ns J m/q IrA 3nj 16I in the proper ratio

for the chlorine lsocc -es Js .s Iell s cleaiji cf the rinl in both direc-

tic.ns (j and b) as expected trcm published umss spectral studies ai

2 o.e t l r i n o n s .'


a a

CI 0 Cl 0

-.--- -- CH 1.... ....b
Th J b
1-r(I+ I-rN








Further proof of structure was obtained by reduction of 5) to 1-t-butyl-

2-azetidlnone (L5) rth zinc dust in refluxing ethanol, a procedure

patterned After chat of Knunyants and Gambaryjn. 'b The same azecidinonn

was then syntheaized in low yield from 3-t-buLylamlnoproptonic acid (.l)

and thionyl chloride.




CI 0 Zn 0 SOCI2
ENON W_ I-BuIJHCHCI2CH2CO2H
N EiOH NI E5tjN
I-Bu 1-Bu

50 51 I




The rin& exp.naicn uas considered t. be of both mechanistic: and synthEtic

interest, and thus further investigation of the reaction was initiated.

Several mechanisms could rcj.onably 3ccounE for the ring expansion.

The first route to De considered wua acid cataly'zed ring opening cf thi

aitridine to glvc an .)-chlorc-i1-a3ino acid. This species might then

react wilh thionyl chloride to form the amino acid chlorLde C(2) which

cculd, in turn, ring close to the 2-aecLdlinone (.,. 'q




0
OLi HCI -HCI
N I 1-BuHlCH2ICHCICOCI
i-Bu C2 t-Bu
52







Secerrl ,bservact.,ns mike chX. r'.uLe unlikely. Ihc reaccirn uith hiLon)I

chloride ar3 not InhhLcbEd by excess soJiu L hdridE. Thn ring expansion

also proceeded ihern .;dtum 1-c-buLyl-2-a=.lrdin=c3rt'xvladce (x ) wa3

treated uith oxjlyl chloride, jnd the yield '.s not diminished when this

recrEion uis rerunn n the Fresence of triethylamine.


0

O/ONa (COCI)2 C'C


I-Bu
26 6.


0
0 t(CoCI)2 r'O0a

E IY, N '
1-Bu T-Bu
29 S

53


It is unlikely that acidic ring cpenin oif the izirdline oulJ occur urder

eih=tr f th- abDoc- b.isic condlil.ana.

Th- second rout ECu be contIdere involve. trans ent fc.rr.:iLn if a

six--r.imbered hV.tre;clc ince radiate (5li via mixed anhydride 5. Sub-

sequcnt loss [E 'uliur dic.rdJ. irom L mighL gnetrice Lth :etiidinone e5).


0


0 7
Bu
C1


0 c, C ,



6/ I Bu
1-RBu b -Bu







Precedent fur the ring contrictior, carn e found in the pyrol:'sis of

p-aCLyl mirL acids where form aion c. aJ ix-membered cyclic l.crrrediaJte

5i) is potLulted.41



0 0


X y L>i. oH

O90H 0


56




Attack by the annular nticroen jc sulfur tinds some 3r..lo y in the for-,.-

clon and isolrticn of oxathijzolijzne h in the reaction d. aziridlnol

22 ulih chionyl chloride.4'



.'OH SOC 0I


I-Bu
t-Bu
22 57




This mechanism, houejer, appears unlikely for several reasons. In

the firsL place, the similar yields and products ob lnred uich cxalyl

chloride =re surgesrt'e of j common intermediate in both reactions.

Secondly, Ehe best available anA4lgies ( Ug, 40f imply chit j (as

well as the unlikely sceen-memiered ring aniloeg re'luired by this mechanism

for oxslyl chloride) wold be stable under the mild conditions of the re-

accLoni. Finally, Lho rin& expansion of 2-azirldinecarbcxylic acid nh)y-








drives to be diCcussed below s is al incompatible itil a 3echnisM in-

volving cyclic iLner mdi.kdus.

A mechanLrjm U-hch 1- capable o explaining the results nr.,olves

interaction ci the unshared pair ot electrons on the annul.r niLrO cn and

the crbonyl carbon resulinrI in iormnatin ocf i l-aizibcyrlo [.l..u j-

butane-Z-one carton (.s. nn examination of models suggecEL chat the un-

shjred pair of elecErons on nitrogen ia oriented iavcrably tir overlap

ac the carbonyl carbon. Tlus the b-nd detc-rmitions and additional scrain

required ifr purticlp.Cion does not appear to be ;escre. Th. resulting

cation 58 m sy then be captured da the 5-position b> cnloride tc generate

the chlorazetidincre ccarling ct rne following bchene:










I I
l-Bu t-Bu

-O-


f -Bu

CI 0 N+
CI- 0
R

i-Bu R '^

47 68
X -0CI, COCOCI







* Analogous p3rtLclpation by nitrc'en at a carbunyl carton has beez used
to rationalize enhanced rateL of hydIolysis lf y-ointn estcra.







Although this ion has nc exact lIterature precedunc, a number of 1-

asabicyclo (1.1.0.] but ine caLcns have teen pu.suloted js re actin in-

termredi 'Ls in ring epar n.ins oi actirdines to azecidlnes. In thio

laboraorry Iolvolysit of azirilinecarntn/l tos.latea (5V ucr6 icund to

give az~etdtlncls (gU) under crtrtin condittl;ns. Thi ring Expansion is

thought to involve a 1- 3ablcyc l 11.1.0.] buto.nnium In (. .' cn inter-
4 ,
iedlrd te


T-Bu I '
t-Bu

59 61


HO


t-Bu

60


W. Gensler and couorkera have shuwn chac the reaction -t Labeled .*zrniine-

carbinyl brcrulie n. aich aluminum chloride in benzene Lo t.fri ring opened

amine ,' proceed chr,.u2h an Z:elidine interediare. It uw. suggested

that this might result frfi a n azabtcyclobucontiu ion represented o. '-


*i; Br

*o2r


A Cl3

C6H
aS


62





SO2 1H32CH2CH 2
63


S 02?0
i-N-



64


1
II*


7'2
g E,








The stability of the azablcyclobutane ring has recently been demon-

strated by the synthesis and isolation of 3-phenyll-azabicyclo [1.1.0.]-

butane by Hortmann and coworkers. T he introduction of a carbonyl group,

as in 5S, would be expected to cause an increase in strain. For example,

Wiberg has shown chat the introduction of a trigonal carbon in a chree-

membered ring results in approxim cely 15 kcalimol additional strain

energy (Table 111).ht



TABLE III


Ring Strain in Three-Membered Rings


Compound Strain Energy kcal/mol

Cyclopropane 27.5

Methylenecyclopropane L1.0

Cyclopropene 53.1



This additional strain would increase the energy of the intermediate

(8), but would not preclude its formation.

If the l-azabic;clo [1.1.0.] butane-2-one cation i _Iwere actually

involved in the ring expansion, the reaction should be scereospectfic.

ALLack by chloride at the '-position should occur at the back side of

the G-N bond, i.e., endo to the puckered ring. In order to test this

hypothesis, the sodium salts of both cis- and trans-l-r-butyl-3-methyl-

2-aziridinecarboxylic acid 67 and 6-) were prepared by saereospecific

base catalyzed hydrolysis of the corresponding arirldine esters ( and

66). These salts were treated with oxalyl chloride in benzene, and the

resulting ring expansions were indeed sterenspecific. The cis aziridlne






(fi) i.avee he c is j ecidinon, ( ,9 and the trans jzlridine (~. Sj g

the trans azetldcnone (j-) ns predijCli The reactllns wntL in high yield

and uich nc. decEtible (nmr) isomeric coitaminatic.n.


I-Bii
67

0


CH, OYa
I-Bu


C OCI02 CL 0


t-Bu
69


(COCIIl

63 !%


CI 0


CH;r' I-Bu


Ihe stcerEopecificitV of the ring expan;ian stru.nly uppurt= tne inter-

irediacy of che l-azabicyclc 1.1.0.] buiJcne-2-one cjilon (_.) rand .n-

equivocally rules oDt the pcs3toility r-f n cr-carbonyl cjatin (I).


0

RR-
r
t- Ba


+ -f0 -
R- R f
R


CI 0

R
R


* Elemnental Janalyss of 6 did not check. However 3ll spectral proper-
Llea were Lir accord with the proposed structure. The mass spectrum
was EssenttLlly idenclcil t hO hLa of i.








It uas hoped further evidence for the tonic mechanism could be ob-

tained from reaction of the sodium a:irLdinecarboxylaces 5(. 67, and

65) utch nosyl and tosyl chloride co form mixed anhydrides (L2). Mixed
.8
Losyl carboxylic acid anhydrides have been isolated, and there is

precedent for their existence as reactive intermediates in some rearrange-
-9
ments. Conceivably, participation at the carbonyl carbon by nitrogen

might induce ionization of the mixed anhydride anJ chus lead again to

the posculated bLcycllc cautions (58.. The resulting cations should be

captured in the '-position by nucleophiles to generate the 2-azetidi-

nones as before.


O I-Bu
R OS A CI 0

-B ,H R0 Nt-B
I-ta
t. BU
R R

72 58 47







Reaclion of equivalent amounts of the sodium 2-aziridinecarboxy-

lates (. 7, and 5) uLth nosyl or tosyl chloride did not yield the

mixed 3nnydridea. InsEcad, mixtures of the sulfonyl chloride and the

symmetrical aziridine anhydrides (7 I uere recovered. The symmetrical

anhydride ( was formed free of nosyl chloride when tco equivalents

of the sodium salt uere allowed to react with one equivalent of nosyl

chloride.




* Nosyl chloride use removed by fractional crystallization, leaving
the anhydride (7b) behind.







The structure oi tib anhydrid. Ia b3Eed on the nrur Epertrrtm (CCL -ch3rjc-

rerisric of the azlridire ring), and absorpclons in Lie ir atc 18'r, ird

17I.0 cm0 1 tchiracteri.tic cf rniydride s;.' Chemldal evidence for rte

a.r.hdrid structure uad oDtained by rec'..ering both sodium -3:sri line

carbox.lace ,.7) and methyl 2--a.iridinecarbuxyclace (i'5, ir-ru, the

reaction oi 'b wisa sdkui, iechide kn nmethncl.


0 0 0

R 7A, Oa "S02CI 1
P'j R
i I I
i-Bu I- Bu T-u


R R H 73a

R CH3, R'H 73D

R= H, R CH3 73c



Strong evidence frr the bicylc ic t ctin 5.' was ibcained ir.w3 tlhe

nir spectra of the aazir'ine enhydrLJes fU7j in sulfiur .Jix ide. 51

cold concentr3red sulfur dioxide soluclon of the cI- jnhydrlde (Si

gave an nmr spectrum in accord uirh the anhydrAde structure A iucre

dilure lution, .1lter SijndiLngi room LemperJture fih-r 3 chortr [ime,

gave an nrr asectrum itch cu-o sets oi signals of stmilir pattern, one

set at chemical ;nifc ch:racterisEi of th-: anhdride, and one iet

displaced downiteld by .n amount -5 ppm ('able IV). BCLh the uninized

d=iridine jnhyJridt .-d the aziridinec:rbo".,ylate ainn are .3silned Js

the species reiponsiblI for the upfiield set of Sgnalj, and [he biLy.iic

cation Structure C(_ isa iaigned to the species responsible icr the

downfiell sea of signals (labdle I,.













TABLE I'.


Cheruic3l Shlits (b.. Ln Sultur Liic.-.i Fl ar. ticc. External
Tetrame Lhyls l ne in Carbon TEtrachlri 3e


Subscrate


0
rj --^OCH-
ti. Bu
I'-s.


0



-1- 0B 1 0
.B. u JH
H H3


S4


0.7aO.i ab

2.76 -.cu

0.93. 0.95


:5 ppn


0. 3c



0.f,


aCounrerion = toylate.

bCounLerton = n,.,late.

CDiiffrence in chEmical Ahtics of anhydride 7IZ and averaEe of Ions
2k'3





5;
Addition of ncsyl chloride or cosyl chloride to these solutions rctulted

In the disappearance of thLi uptLeld set of s3Lnals and enhancement of

the *j,'wnt Ild sec of signals, presumably by ionization of che ne'-ly formed

mixed anhydride (_ .



I-Bu
0 0 +

0- rSO2CI SO r AO
I I
I-Bu L -Bu
H CH3



72 74



The value of .5 ppm (1.00'i observed for the ring hydro.bns oft i

quite similar to that observed by Olah (L.U10 for l-L-bucylaziridinium

Ion in boEh antimony penta'fluor Ld-sulfur dLo'tde and acidic sulfur

dioxide. Ihe chemlcdl shift of the c-butyl group (5 0.7;3 is not simllar

to that observed by Olah a.id SzilagyL (5 1.,e)."'- This discrepancy can

be rationalized by differences in counterion, solvation and concentration

eftLecc, *nd anisotropLc effects due tc Lhe bicyclic rlnt.

Further chemical evidence for the bic-'clic cation ()j was obtained

when the sulfur dioxide solutions were quencheJ which Lecraethyl mrc.n-iu;,

chloride Ln aceconiLrile cc strreospectiLcally Live 9 .





* Clah and :.'iLlagy observed differences in the chemical shifts cf the L]Mn.,
aziridinium ion tf as much aa u.; ppm uith chanrea in [H ] and geenlon.

















t-Bu
I

S-2. H 0 EvlJCI

C H3N
r I-Bu
H'-CH






74 69








Similar result -ere obtained with the trans anhydride (7.cl A

sulfur diokle solution of the annydrlde (.cj in the presence of nlsyl

chloride initially showed tvo sets cf signals attributable to the

unionized anhydride and the carboxyl3ae anion (uplield set of signals

and the bicyclic cation (_L) downfieldd set of signall, but decorposl-

Lion was so rapid chat che spectrum obtained was not at all satisfactory.

At -20c a clear. spectrum of the bicvclic cation was obtained. Again,

values of 6 and -5 ppm for the tertiary bucyl group and the ring hydro-

gens were in accord with expeccations (Table VI. On warmnin these

signals disappeared with concomitant formatiun of a rew set of signals

attributable to crans-l-t-buryl-5-chloro-b-mcchyl-2-azetidinone (7Q).














TABLE V


ChEmical Shitri (5) in uulur iloxide Relactve to Exrernal
Tecramethylaitlan in Cjrbon Tetrachloride


Sub;icrJL


0 *-Bu

OCHl3 HOCH

t-Bu
CH.


- 5- p *


* difference in chemical shift of ester and ion 75; it is ipparenc
from lanle IV ihjL the rmechyl-2-aiLrldinecarboxyljct 1i a lugit irmt
model (nmr) for cie 2-.ziridlne aihydrlide.










0O 0
0 S02
~~-4
NI N
I I
t.Bu ItBu

73c


0
. O"
'r'N +

t-Bu


NSCI


0



t-Bu


r-







CI






t-Bu
70


The rirn expurn.sLCn oi the nrhydriae could 315l be E cLed in

acectonlirtle. CGood }) ld3 of '-chlcro-:-._ecriJdnnes '. ere olrtined

uher, th-: iridLne jnrndrlar iE (i and 7 :.b and ncs,'l chlerlie uere

dissolve. in a solution of exc-ss recTrtehyl arr ornlu- chlorid-e Ii

.jCce ori r i ie.


0 0



I-Bu f-Bu


NsCI

EI4tMCI
CH3CN


R=H, 73 a



R-CH3, 73b


Cl 4

R

t-Bu




50 171



69 75 %







It is pertinent to this discussion that, Alrhuug ;W-et-.ritrtle is

well estEblithed carboitum ti.ur crap,' no detectable amount of lonic in-

cermaedriate uws intercepted. inmi Is In accord with the observ-atiur.s of

Leon.rd that ;az rdinium orns do rot re.act directly ulth icetcnitrLle.

RirLn opening lo aizrldinr.um icn ., rcc fcrn a nore stable carbnium raon

occurs prior ctc reacclon i rh acctonltrIrile.










CP CN3 CN.


CIO4 CI C104


76






The postuljted int riE di3jte (5i. is, Jmun. other things, an ziridlri am

ion and thus would not be expected to react utch ccEccnitrile.

The ring o.p.arsion of che jziridin. ar.hydrides coni. ncin-ly rule

out the possibillc y of any cyclic ir termediate (.i) sI uih a3 dimcu .sed

previously. The direct observation of the bicyclic tons (71 and 15j in
54
sulfur dic-ide rules cut any concerted ,eitnondo.imic t in exp.niton

of the anhydride








Cl) 0

CI [0
X CI 0
v-Bu
IBu I-Bu








The observed increase In yield of 2-izeildin.ne uith netryl substitution

at the i -rositi in the reoctLon of the aziridinE jalt. ith oxalyl

chloride tl also no~ in accord uith g cttonodearjic retrrangcEent.

O
R O. tl
R' Rt

r-Bu A' "'-B

R= RH ; 5_ 50 26%

R=CH3; R=H; 67 69 79'.

R:H;R-=CH3, 68 70 631.


This increase in yLeld Eiuy reflect steri inhibition of nucleuphilic

attack at the 4-position (rcuteC B) of the cation. Such CtLack, leading

tu C-laccarm furmncion .", might caopetoe Lith atcrck ad the 3-pLsi-

tion (route A' leading to 2-azeciLdrnone formJtion. It would ,e Interest-

Lng to see if the yield further Increased nith .,'-dieBthyl-2-u:tridinecar-

boxylate. Similarly, one might predict subEcitucion at the 2-posl iun to

inhibit 2-jzcLtdlinone formation.











CI 0
f-Bu


H-0 R I B u



c B i P R

58 Cl 0

t-Bu


77



It a. ch.uuchr the rh .-thlor-.-j..-ectidin.one miht rd.Jil/ lend

rheiisel,.'es to in na.r study ir. acrimony pencjaluc.ride-sulfur Jixid*d solu-

SJcr.. AlkT l halid-Fi, ihen dlssclc.i1 L. r.l = soluti n, _nt.:.- to -;i-

SLrbll a'lutions of Cdrb3aniu L...riS Chich can be oblercJ by nmr iotC-

crc.scopy.


SO2
RX + SbF5 Rt t SbF s -





With rint in mini, l-c-bucyl-j.-chlc.ro-2- i'rCidLn.ne (Li .-is Jitsolved

in u s, ur[dEd solution o t nc irny pentailuorlJd In sul ur dioxide. The

iar spectrumm of the rsulting soluLtin compared co th, of the .?-

cidinone (5)) in sulfur lrixide (relj ve to Excrrnjl TIS Iri CCIh COn-

siderable downfield shifts were observed (. ppis. Table VL, for the








antimony perntarlucrie s.:.lutlns, but little change in the splitting

pattern r s noted. SLmilar results uere eotaLrne ulth cts-l-t-buryl-:-

chlcrc-4-methyl-.-i;sz dlncne ('i. The specter, .o the antimrny pcrta-

ilucride sclulioj ln are quie different irci the sulfur divide specra

cf the sare supposed i-ona generated ircn the inhydriU presutlrrs. The

charges in the chemical shift (.: ppm) are rcl and ire reasonable for

what b ne milht expect for jamEniuiiim ion ioritLEtln. In fact, they are

jrearer thln the value ofi L ppm observed tcr triethyl n;ine and

ceLraeth)l anmrionium cnlorti a model -yrtem whichh neglects all anlsc-

crc.pLc effects of the bicylic rlngs (T=ble VI).






TAkLE VI


Chemical Shifts (5) Kelative tc Etternal Tecramethylsilne
in Carbon lcrnahlori.le




CompcunJ P. So O5-SbFt L ppm


E-Bu 0.75 1.15 0.10

CI' 0 He 4.08 4.89 0.81

HbN- Hb .18 4.02 0.84
Ha 'f-Bu
Ha 2.70 ;..59 0.89







For nydrocens tuo carbons removed frorn cAdron center -hilts of
0.8-1.8 ppm are common '











TABLE VI (conc'd)


Compound






CH3 l
Hg' IlBu


50 sOI' F5


f, ppm


0. 35

0.75

0.81
O.14'


0.19


0.51


CH., .oS6


Hc.we.-rr, uhen l tcmpts were rijde to quench theie supposed ione uleh

nethancl according to procedures used by Olah5 to quench similarly fcrEd

carboniunmi onw, only the r.riginal chlorcazetidinnes cculd be recovered

These results are interpreted as Indicj in& donor-acceptor complex fcimL-

tLcn, pru.bbly eiLher ulh oxygen and/or nitJiger and antimony pernta-

fluoride, but nut toniation.








I Bu
S SbFrCI

C O 0

CCI 0
'l-Bu SbF,




I.Bu

DONOR-ACCEPTOR COMPLEX


It is nrot surprising thtL ionl;adLln or the chlorojzetdinanes (fm

t3lls tc occuT. DitzoniLu ion 7E recently has been generated in the

cephalosporin series.1 This ion, In the presence of chloride, underLoes

a di rlacemeon cc. wrm the chlcrocephalocsporin (79). Thr observed inver-

sion ci coniiurution suFggess that the reaction of 18 does not prucecd

by loss ot nLcrogen to l Ve the bicyclic ion ( .1i. Fcrnmation and capture

of ij would require retention of c:nfigurailon.

.4-
N2 S Cr C1. S 42

t0 2A CH20Ac 2c
kCH O~c O' c

CO2CH3 CO2CH3
s .



H 20 Ac
C02CH3
80


The reluctance of the J-subacitured-2-azecidincnes to ionize to the bicy-

clic cations can be rjatincllzed on stereochemical grounds. An examination

of crude models shous th3r the unshired pair ot electcrna on nitrogen is







not .rienLed fivorjbly ior overlIp it the inc Lpienr calIon center. Con-

ilderible b.hd deforniat[rn, arn hence scrTin, I. required icr particlpa-

ticn and thus i.nizati orn Lo u.ccur. Furtcermcre, the planar mid.I linkage

would pre.uimabl inhibit such a dezrrn-ttcn.

Formation .ci bicyclic catirn ('1 is in ccnEraJ to te lonizrtion

of the crsyl V --imlno cid rrnndride (,1)i deqcriDed by Sheehjn and

Frinkenie d.1c In chIE sa~tem ir a,ecnt icn occurred to c:l. the tvsyl-

ate anion, a Schift b3ae (i i, and cjrL'bn monoxide, presumably vi, par-

ticipation of the electron pair on a rrcgen-



0
2C- 2 20- Ts C1 2Cnc-I.0% + -CO + ObT

NHO N-H
82


81
il



Thi analogous reaction in the azirLdine sy' ceEm would have generated the

azririnium ion L.). Although zuch cjtions irE known, they are reallyy

destabilized by ring, EraLn.



0

N N CO + OTs
I I
-Bu t -Bu

83


- The mixed anhydride kj) was notc aolated.







Atcernps hja been rjde ct extend the ring exp.aslcin co 'ziridlnes

ulth other .iibscltuencs cr nitr*.Een, utr to no avall. lieverthele~s,

hope still rcrarins ctha suitable cnditlons will be L[und LL nuke this

rccticr. more gcereJi rad syntlheticlly useful. The potential Lioctlni-

cal uillity of the 2-ar;etidinnnes makes such a stereospecritc synthesis

qult- valuable. r. aCtttpt has been mjde cto extend the ring expanslsr

to other ret-rocyclic rinjs. Hocev'r the pcsslbility of such exEen.ncn

Is censider-d tr b- a EraLr co both synthetic dnd mecliantisr c Interest.




E.sic Hydroljsis oi '-Hl.lo-2-n'ecidinones


Basic hydrclysts cs 2-a3a~tdinoneu generally leads rr, high yields

c-f b-arninc. ':. iis These reacctin hrave receive d cn.idertle aCcEntion

in the literature. A. D. holley has icund that [he rate ri ihdrolysis

ij v-r.' -.ch fui- ::n .f th[ s,.- tc i nr. on Che rinE, -ni it Is pre-

sumrd that thi: ecfecet a the result of a combinction of scerlc and in-

ductive eifeccE As one might predict from strain arguments, the rJtes

ct hydrolysfs for '-jecidin ones are greater than thuse for pyrrnlidrnec,

uhich in turn jre greater thin these for N-nethyl aceLtaide.65











TAbiLE VII

Apparent Second Order PRe Constanri for Hydrolystsl A
(0.5 11 I CH1/65'. Ethriol, 50)




ound 10 -2. (Iicer-mol-lsec)


015.0

H

0
1.0



,0
CrON H 0.4





CONHCH, 0.0,


Bsilc hydrolysis of the 3-cnloro-2-azeLidinoneas Q.,) led not to

the amino acids, bit to the a2irldinecarloxylic jcid systems. I-t-

guryl-)-chloro-e-qzecidlnone 5 g IvE good yieldr of sodium I-t-butyl-

2-aziridlnecarboxylJcc (Dj and methyl l-t-butyl-2-aziridinec rboaxylite

() when Ereated with aqueous sodium hydroxide and uith methanolic

sodium methoxide respecti'.'ely.


Compi









CE






0CH



CH2


a>









0

s77A 0N a




f-Bu








Similar ring contcrciclons have been observed In the analogous carbo-

cyclic system. For example, Conia and Ripoll" have treated ,j-tromca'cclo-

bucanone (14 wLth aqueous so.dium carbonate and ulth sodium amlde in

liquid armm, onia and recccvered c'ycloprcpanicarboxylic acid @60)J and c;.clo-
u i- 7OCH3
















propanucartcxamide (.n) respeccLvely.
50
















84 N "H2
SimThe echan proposed or thee ring contract tions involvegous inLtial
cyclic system. For example, Conot and Ripoll 7have treated '-bromucj,clo-














abuack on the bie aqueous cr.dium carbon, aloed b h ac s ium amble in



iqid aereospec.Lc as one might predctc. Tranrs--bric id-j--biuyl0 clo-
VA OH




84 NH2





The mechanism proposed for theue ring contractions involves initial

attack of the base at che carbonyl carbon, Eollowed by what is probably a

conccrced ring contraction giving the observed products. The reaction

is atereospecifLe as one might predict. Trsns-2-brcmo-5-t-batylcyclo-







4I7

Ducjnone (n.) when traced wulh equec.us sodium carbonlr e give an 3pprox-

imately qluntltaci.e yield of crn~;---t-butylcycl oprc.Fpnec.rboxylic

acid ) 5 .





0 0) Bu. 0
H- H, 0 Ho

f-Bu 'Br -Bu Br



.1? 88






A iechaniia similar to the =boie miaht be involved In the t ng

contr.ctior, of the -chloro-.-jec t*d nones. Attack of hbse at the

carbonyl carbon probably occurs prior to ring contraction rro eid.ace

Is ,.ail3ble which can unequivc.;lly di tinguish beric-en j c-ncerted or

a nonconcerted ring conrectrlon seep. The rino contract ion i acScreo-

specific however. Cas-l-t-bucyl-'-chlcro-h-ameth.l-2-azecidincn ('I) on

treajtm-nt with sodium hvdrcyidE in aqueouG dirCane gave clean Sodium

cis-l-t-bacyl-y-mechyl--.jzIrldin cerborylte () ). Similarly, trans-

l-c-bucyl-j-chlcto-h-mechyl--azecidinone ]) gave the trans azirdiL'c

sodium salt (,.) on tratmncn with base In the hitter case the reaction

was not at all clean. The structures of the other products of the re-

action (which comprise about 5n'. of the reco.'ered mcerial' uert no cM e-

Lermined, and thus it cannot be sand with certainly chat none of the

cs salt t) was formed. In spite of this it does follow that the ring

contraction is stereoipeci.ic.
















0





O C H-'
C Bu -Bu
69 67






CH/' t-Bu -Bu

7 06






A dramatic difference was noted in the rates of hydrolysis of the

various chlccazectridnones. [c. quantitative rate daLj are available, but

it can be said tnat the h-methyl-.'-chlor.--azetidlnones hydroly:ed at

a lower rate than the un ibltLtuted chlorcdaz eciLdnoni ( V0 as ? hr for

complete reactccn at ref l't temperature). it is suspected that this

difference ia due to a similar combinaciun of sceriL and electronic

effects ihich plays o important a role in the hydrolysis of the azetidi-

nones studies by Holley and Holley 6

It might even be suggested that the rate concr lling step of tht

rLng contraction is hydrolysis to give the s-chloro-d-amino acid (9)

uhich under the basic condiLions employed ring closes stereospecifically

to gije the azlridinte Gabriel Synchesta). This might also explaLn the

mixture of products observed for the ring contraction of trans-l-c-buryl-

5-chloro-l,-meBhyl--aszcLidinune. The intermediate amino acid (9) could

conceivably lead to several products.















R I-Bl r 1-Bu






iR u 0 i-BuIHCHRCH HICO2

1-Bu __









The ring conrjct ion does ufg esC the pcssibillry of a synrhiticaliy

useful sterecspecific rcurte cc the 3zfrtdine system. LErension ofi he

reacCion to ajecidincnc. ulth ditferenc subsituents, for inscrnce aryl

subsrtiuentc, has not yet been temptedd














CBAPR ER 11


PYROLYSIS OF TP.LPHEI YLME IHfL 1- t-BUTYL-2-AZIRLDUJiCAPBOXYLATE

One of the more theoretically intriguing and yet still more elusive

systems waiting to be synthesized is the 2-autrLne system (0). It

has been suggested that this cyclic class nf compounds itch potentially

four pi electrons could be anctaromatc. f For Lhis reason it might

be expected to exhibit some rather Litreesting pcrperries. A few un-

substanriated claims for 2-aziri.es can be c-und in the literature,7'7

but an authentic 2-azirrne has yet to be isolated.


R R


I
R

90


The hope of generating and studvyng a 2-azLrine was the driving

force behind the investigation of the pyrolysis of trlphenylmachyl

l-t-buLtl-2-asiridioecarboxylace (91). it was thought that heating

this eater in a suitaDle solvent might induce Lonization to form the

trLphenylmethyl carton and the carboxylate anicn (I.. Since the

triphenylmethyl cation has been shown to be an effective hydride ton

abstracting agent for hydrogen atoms a to the nitrogen in alkyl

aaines, it was hoped that hydride ion abstraction from the 3-poal-

tion of the a.iridinecarboxylate anion by the triphenyltmethyl cation







generatEJ In situ would occur wlrh simulLaneous or subsequent dccar-

bamylaticn to produce the ilrst member (9' oi the long-sought 2-

azirine system. With luck, this could be trapped utch a diene to form

a Diels-AldEr idduct 74i).


0 *C 03

,

I-Bu f-Bu


-C02 03CH




S N-t-u (

t-Bu
94 93


It might be noted that Chia proposEd decarboxylation is quice anal-

ogous to he decarboxylacion ir 3cecone fI the anion ou cinnawic arid

dibromide, an apparently crans E eliminacton.1'


0 E- ._Br

B\ + Br c C02

H H H H



Triphenylmethyl eaters of aziridinE acids h3d noc previously been

prepared. Fortunately, published procedures for the turminatcn of c-her

criphenylmeLhyl eaters from the sodium salts of the acids proved sat-

isfaccory.74 Reaction of sodium t-buc/l-2-ailrldinecarboxylate Q5

itch triphenylmethyl bromide in benzene gave the desired triphenyl-

mechyl L-t-butvl-2-aziridinecarboxylace i(9 in a reasonable yield.







This ester was a solid and was quite cable when in a pere stcae.


0

-Eu orIo
N-ti
I-Bu


i3CBr

C6H6


0

C T-

?-Bu


523 9




The ester (CLJ as heated in a sealed cube in benrene st 180I 1 0

for fourceen hours. When the tube -as cooled and opened, a notice-

able amount of pressure jas release suggestlue of gas evolution

(dccarLboyldaton). Ts.c major componcLts, rerreaent ng about 9:'. of

the reaction were recc-vreJ iron the reacLion mixture and character-

izod as 1-t-butyl-l-triphenylvmathylaziridine (, -57.) and IJN--buy'l-

tripher ylme chyl rethy lamine (., I'.).


0

JOC C 0 3 C03

I-Bu C66 1-Bu
I- Bu i-Bu


+ T-BuNHCH2 C'3



96


These products were not suggestive of 2-aririne formation. Never-

theless the problem of the mechanism of formation of both products

was considered incriEuing. Several routes for decarbcGKlar.on to the

triphcnylmethylarlridine are possible, one radical (.s and Evo ionic

(B and C). Formation of the amine ('_ vwas unclear. A control experl-

ment showed chat the trlphenylmeLhylaziridine (9) was stable to the







recciLion con-ditions and thusi i not the source of the amine (C.


C' O3
CO2

f-Bu

0 -CO3
,7' '0003 B -.C- 2
B ';-;'. COp
I
t-Bu I-Bu


91 +c3 C
m7 CO2

I-6u


I B


95


Decarboxylltion of triphenylmethyl esters via a radical path h s

becn suggested before alclouhi the data presented did n.c sePi- to

unequivocally demonscrate the exiseoce of radicals. The possibility

of a radical path in chl aClrzlnne system i as investigated by carry-

ing out the pyrolysis In cu ene, a knaon and etfectci.e radical trap.

Radicals abstract a hydrogen atom iron cumcne to form a cumyl radical

which then couples with another similarly formed cumyl radical to

form dicimyl (j. i Thiu tre presence of dicumyl is eJidence for the

presence of radlcalr*.



H R b_





97








Conversely, the absence of dicumyl suggests that radicals are not

present. Nleverchelcss it is conceivable chat cage recombinacion of

the radicals is so efficient that intervention of the radical scavang-

ong cumene cannot occur.7

The pyrolysis in cuzrene gave a practically identical product dis-

tribution as pyrolysis in benzene, and no detectable dicumyl uas

formed. Analysis for dicumyl uas done by gas chrormaography, and it

uas estimated that as little as 1' of the theoretical amount of dicumyl

would be detected. Thus the radical mechanism was deemed unlikely.

Studies of the decarboxylation of carboxylic acids indicate that

generally decarboxylation occurs to form the carbanlon. The reaction

is facilitated by groups which stabilize the carbanion centers, for

instance electronegative heteroatrms. No example of carbonlum ion

formation via decarboxylation of carboxylic acids is kncwn.8



A +
RCO2H R" + CO2 + H





Thus it might be expected that decarboxylacion of the eater ( l) is

occurring via ionizatcon to the triphenylmethyl cation, followed by

decarboxylatron tor form the aziridine carbanion (Path C). The problem

was to experimentally verify this prediction.

It uas thought that a distinction between the ruo ionic paths

(B and C) might be made via a trapping experiment. For this reason

the trLphenylmechyl ester 91 was pyrolyzed in methanol. It uas pre-

dicted that methanol would intercept the carbonium ion to form a methyl

ether. The carbanion should pick up a proton. After pyrolysis methyl







triphenylmethyl ether was recovered, indicating that ionization to give

the triphenylmiethyl carbonium Lon had occurred. Unfortunately no other

species were recovered from the complex reaction mixture.



0
r 3OC03 3C0CH +

1 CH OH 3COCH +
t-Bu 3

9J




Since no azirtdine fragment uas recovered, and since the change in the

solvent was so drastic, it is not valid to claim that the decarboxyla-

Lion occurs necessarily by path C merely on the basis of this experi-

ment. It is felt that formation of methyl triphEnylmethyl ether is at

least supporting evidence for ionization as indicated in path C.

Addition of a proton source to the reaction medium should allow

capture of the carbanLon to give either tripnenylmetha.e (path B) or

1-t-butylaziridine (path _). L-Butanol uas chosen as the proton source

because, although it uas capable of protonating the carbanion, it is

not a good enough nucleophile to cause transeaterification or hydrolysis

of the triphenylmethyl ester. Pyrolysis In benzene in the presence of

one equivalent of t-butinol resulted in a clean reaction yielding the

triphenylmethylazirldine (95, 11'.) and 11-t-buryl triphenylmechyl-

methylamine (96, 88"). In addition, when the benzene solution of tne

reaction mixture was washed utth water and the uater wash treated with

dimedone reagent, the solid dLmedone derivative )( of formaldehyde

was recovered.














0


1 CC 6
-f 0C3 C03 i-SuCH Bu H
7r7 Ni-BuJHCH2C03 + H2C=O
i C6H6 I
I-Bu I-Bu

96


91 95





Although thi- experiment did not serve to dileerentiate between the two

lnic route t tthe triphen.lmethylaziridine, it did suggest an explana-

tLcn ior the formation of the secondary imine, which in turn sheds much

liiht on thLi a:,scem.

A most reasonable mechanism tot the formrnlron oft I-c-butyl criphenyl-

methyl.ieLthlmine (,I' intioles formation of a 1,5-dipjalr species (99.

There are numerous examples where the azridinc ring opens to iorn a

1,.-dipolar species in this sense. 8 When protons are present in the

system this dipolar species can be prutonated to give the iminium c cLon



* Precedent for protonation of an, aziridine 1,-ldipole is cluLmed in the
reaction of ethyl trans-l, -diphenyl-2-aziridinecarbox vl te (i) with
t-butyl iscniLrle In acidic carbon tetrachloride to give a ketenimine
(ii); J. n. Deyrup, to be published.
0

C2H5 t-BuN-C
C-NCH, 02C2H5
H CCI4 C C
H 1-BuN








.10 81 Because of the positive charge on the nitrogen this Ion should

decarboxylate readLly vi ori ionic route7 to give 3 new iminium ion

(101). Hydrolysi; of thc Ijn wiuld generate the amine 105 ard irtc.l-

dchyde, the observed products. IE the dipolar species (99j is in equil-

ibrium "ith the ester, the cripherylme chyli3ridine (9SI arises ftcm

the ester, and the amine (.in and formaldehvde arise irom the 1,.-

dipole as sugei;ted, the addition oi t-bucancl would tend to intercept

the dipolar species and give :he observed product distribution.







0
^ OCO s- ..C03 H t ,OC03
X-. -------- N
S0 i 0





S- C02



CI-u 20 C3-
I-Bt'
H 2CO t- lu JHCHC2,3 N- 'C?3
95
?-Bu

101



If the lecarboxylacitn yielding tne triphcnylmethyliairidine (.51

Ls indeed proceedLng via an azaridine cjrbanion, as is pcscularcd here,

it should be possible to generare analoeous azirLdine carbanions by

other routes. Ii such procedures can be worked out they should be

valuable as still another route to variously subs9ituced aziridines.















CHA T'EP r',

EKPERIMENTEL


Th. mrlLin Poc-ints uere determined On a Thoias Hocver C pillary

Helting Point Afppjritu: jnd are uncorrected. boiling pciLnts re re-

corded as the temprairure it which h the M[IirEijl istll3, are at

.acrc.hspheric pressure unless c-thcrwise n.ted, .nd jre uncorrected

EvJ3poratl'. diatLilationi jaEre peric-rped on sr ll ;iample' ci ucaerial

Lollc.airb tch '' uc rohri procedure vi Craeae and Uihl.

Tre mnira-rei sTe ctr. were recurdeJ o.n a Perkin-E lr.,Er Ir. irunenc,

Adel number 1;7.

The routtr E nmr speccra j-erE recorded on a variaL Asi i cs s r C i-

60-A r, me erc c le recc.r-Jin spec trcoir er. r The ,-r .lata .re prepenctd

.s fullo us: chemaical AliLft (aplicitng FatrErn, number of hydrogen.,

coupling constjnr., js31;nmcntI'. Chmirtc l shlic s re e);presire in parts

per million and rt carbon cetrachloride and chlroroerm are relocive tu

internal tccrS;eclhltlIne. In deucerium oxide chemical shiits are

relari,.e co a position I 99 ppm upiield from the DOH signal.4 In

sulfur dir.xide chemical shirts ire relative to external cetracweth.l-

silanc Ln carbon tetrjchloride.




e s = sin:lt, d = double; dd = duublet ui doublets; t = tLrplec,
q = quartet; m = oultiplct.








Molecular eight were determined by mass spectrometry. The mass

spectra were recorded on a RMIJ tE mass spectrometer it 7u ev. The

fragments are reported as m/e (relative intensity).

Microanalysea were performed by Galbraith Laboratories, Inc.,

Knoxville, Tennessee, and by Peninsula Che.research, Gainesville,

Florida.




2. -DlbronobuLyrtc Acid

This was prepared according to the procedure of Michael and

Norton. 8


2.5-Dihrcmobutyryl Chloride

Thlonyl chloride (130 g, 1.1 mol) was added to ',5--dibromonucyric

acid (181 g, 0.74 mol) and the resulting solution %as gently retluaea

for three hours. Distillsaton yielded 167 g (86'.) of the acid chloride:

bp 95-100 (20 sm) [Lit.1L20 (20 mms);8 nemr (CCI ) 5 1.95 (d, 5, J = b

Hz, CHJ, and 4.49 (m,2, CHBrCHBr).



Mechyl ',7 Dibromoburyrate

2,3-Dibromobutyryl chloride (l67 g, 0.055 mol) was added slowly to

methanol (2 g, 1.0 mol) at room temperature with stirring. After ten

minutes,excesa methanol and hydrochloric acid were removed by rotary

evaporation, and the residual oil was distilled to give 158 g (96,) o[

methyl 2,3-dlbromobutyrate: bp 10>-106 (17mmi [Lit.1250 (48 mm)]; a

nmr (CC1 ) .5 1.9u (n, C, CH,), '.80 (s, 3, OCH ), and 4.)8 (m, 2, CHBr-

CHBr).











Methyl 1-t- 6 cyl---.A:z ridinE:c rD'.','lact (5)

Thli was Frepared accorlirn to tre pr.-cedure of C. L. Moyer.L41





Meltyl I-l en:/l---..lridtric ro'rD~ ,'ate (ll,

Methyl -,.-dlbromrc.proplrnat (9.0 0.15 mcl) jwa dis5olved in

benzene .J) 0 al) Ln a Lhree-necked fIla.k equiFPed LLch an overhead

stirrer, dr-. ping tunnel, and condenser, and the flask was immersed in

an ice bath. iriethylamine (43 I, 0.45 mel) uwa added in a dropwise

fashlcn fi'll.owed by ben-vylmine (1, , 0.i5 i ,). ihe re-c:.on n.LsXurt

was refllxed rverr. ht, th.:-n co-l.d to- rooi cempercature and the solid

ajLne hyvdouroricdes were recr'ved by itltratio.i. Disrilltion of the

thick oil Lift matter evap'rtiLon of the filLrate Eive 22.7 (79.) Gi

methyl l-b-er.z l--a; lridinec- rbox.l.t (. .): bp 90-95P (O.. mm) [Lit.

1 =:.' (5m.)1,65 ir (liquid fil'i 17L5 (C = )., 75', and 0 9 cm (phenyl);

nir (CC1 ) 5 1.50 (dd, I, ring proton), 2.02 (m, 2, ring protons), '..hl

(q, 2, CCH,), '..5.' ( O,, ( Cli), and 7.'u (a, 5, C ).

Anal. Calcd for ( llH I l2: C, (9.09; H, N,.735; N, 7.2.

F.,und: C, 9.0, 8, '7.0,,; N, 7.2'u.




Methyl l-Pnenyl-_-.s.:;rid[necarbo'j.lt (7)

Hkthyl ?2,.-dtoiomopropiunate (7T g, 0.28 mol) was dissolved In

benzene (200 ml) and cooled in an ice bath. Triechylamine (c; g, 0.7

mol) -as added drop.tse to the stirred eslucio'n as trithjylamne

hydrobromnid precipitated. [hen aniline (28 g, u0.. mol) as added,







and the reaction mixture was reiwlued gently for 12 hours. The amine

hydrobromides were removed by filratLon, and the crude oil lett after

evaporation wus disLtlled to give '4.' (69'.) of methyl l-phenyl-2-

azetidinecarbox)Iate (JI: bp 92-100'' (0.5 mi) Lit.95-105o (0.; rnn)],19

Ir (liquid filn) 1750 (C = 0), 754, and :95 ciu-I (phenll; nmr (CCl1)

5 1.1 (dd, 1, ring prrcon), 2-.t (m, -, ring protons), (.6' (, ,

CCH,), and 7.0 (m, 5, C H).

Anal. Calcd for C1 H I : C, 7.76; H, 6.26; r', 7.9C.

Found: C, C7.7'; H, C. 5; Nt, 7.86.




Hethvl Cis -l-t-Butsl-'-Mithyl-'-- a'ridinecartboylare ftr )


Hethyl ?, 5-dibromobuctrate (100 s, 0.58 mol), triech lamLne

(1(O g, 0.9, mCl),) and methanol (400 ml) were stirred at rton t nepera-

tLre fir three hours. t-Liiylamlne (70 g, 0.96 mol) was added, and the

mixture was allowed to stand at ro')m t Lperature for two days. Water

was added, and the solution was extracted ewo cime; uith benzene, dried

(MHSO ), 3nd evaporated to an oil which on distillation gave 50 g ('.'

of a mixture of cis-l-t-buryl---methyl-e-aziridinecarbhoitlae (, )

and trans-l-t-butyl-i-mechyl-'-aziridinecarboiylate (f_. 1"' ). The

pure cis isomer was obtained by spinning band distillation. bp o5
-1
(3.0 mm); ir (liquid film) -900 (CH) and 175l cm-1 (C = C); ror (CCl;

spectrum N.o 1) 5 0.95 (s, 9, E-butyl), 1.17 (d, :K J = 5.3 Hr, Chli,

2.05 (m, 2, CHCH), and y.65 (s, ;, CCH,1; molecular reihtE 171.

Anal. Calcd for C. H 110 ;: C, 6,.1:; H, l'j. l; N, 8.19.

Found: C, 6-.0 ; H, 9.99; N, 7.95.









Herhyl TrInn;-I- r-..jrl--'trthvl-2-Azir i Iinecarboxvlat e ico)


Methyl E, -d1brormobutyr.ate (o F, 0.10 mol) and crriehylamlne

(?9 g, 0.015 nol) '.ere disolrved in benzene (50 ml) and left at room

temperature c,.e.rnitht. The jmine hydrobromildes were removed by 'iltra-

Licn, and the filtrate wa evaporated ro an oil. The oil was dii-

solved in t-bucylJamne (18.2 g, 0.25 mol) and left at room temperature

for .tur dayv. The arlne hydrabrcmides were rer.oved by filtration,

and the fillrate was evaporated to an oil which on dLatillation gave

12.1 E (72'.: of a mlLxticre of cis-(_5.) ind trana-(~t7-) methyl l-t-

but l-)-netrhy'l-_-astrsi.necarboxylate. The trans isorer (ro) was,

after wjshirj uIrit a4ueoua sodiu-n c rbonate, completely separated from

the Cis isoaer by spinning hand distillrlion: bp o5o (Li.2 nm), ir

liquidj illn'i 245, .'CHl', and 17 0 cm 1 (C = ') ; nmr (CCI ; spectrum

No 2) 1.10 (s, 9, t-bac; l), 1.)21 (d, ., J = 3.' lHz CH,), 2.15 (d,

I, J = 2.4 l H C.. 2.46 (C 1, C.), ..6) (s, :., O IC ); molecular

weuLht 171.

Anal. Csled for C.H O: C, c6.l, H, 10.01; N, 8.1B.

Found: C, 6 ;..4;1 H, 10.16; 1 8.,1.



Rin.ction of 1-E-Bucyl-'-A :ir dir.ecarb jr.lj e il.i With
h=ydra:irnc idrit.' in LtLhnol -

Methyl l-t-butyl-2-ainirdinecarboxylace (, 1.r5l 0.01 mol) and

hydrazine hydrate (1.0 &, 0.02 mol) were added together with enough

ethanol (L ml) to effect solution. The solution was refluxed for five




* This is a standard procedure for making carboxylic acid hydrazides.l1







hours, cooled to room temperature, and the solventr was vaporalied

Evaporative discillaricn of the residual -.ai gave 0.91 g (t:.5) of }-

r-burylaimlnopropionic acid hydrazide (.: bTp lO0o (U.1 m); it (nujol)

3140) (tM) and Ir55 cim1 (C = 0); nmr (D 2i 65 :.25 (s, 9, c-butyl),

.'.54 (m, -, CHI,), and 2..99 (m, ., CH.), molecular wEight 159.

Anal. Calcd for Cl1Nl uO: L, ic 80; ii, I.).7c .1, 26.39.

Found: C, Il.56, H, u1.5S N, 26.17.




l-l-Bui'dl-;-- ZLridne arojoxllic .?cid Hy,'ra.Tide (41

Hethyl 1- t-huryl -'-iAz rid-inecarboscylate (5, l.5i7 liu.ij riol)

and rydrazir.e hydrate (0.4t g, 9.0 mmol) uwre stirred at room tempera-

ture for 9.5 hoara. The resulting oil was then triturated wtuh cyclo-

hcsane. Residual cyrlarexane was then reraoved by Evaporation in vacuo

tc give a cr .r r,.!. --r cbserr.' icr oi ..h oil i ndi 1cat I tc L.;

of the L-but)l concaninG species present as t he a:irLdine ihdrazide

U). Alao Fre.sent were some mirLhanl and Ftartnir. ester: nor DUO0;

spectruiii No 5 .5 1.2. (', 9, E-butyl), 2.17 (m, 5, ring protons), and

2.64 (dd, 1H, ring proton).




l-Ben-yl-2'-;z: iinecarbosu1lic ;e- i Hdra lde (1


Mechyl l-ben:yl--sn:icrdindcarboxlace (2i, 15 0.0'78 a:ol) and

h)drazine hydrate (3.85 g, 30.077 nl) were stirred together ac room

temperature for 40 minutes. The reaction mixture was then seeded -ith

a Ball cry.Eal ci Lt and i.e reaction mixturee solidified to a cake.

Accempted recrystallizjcioo irom benzene caused Bsom decomposition.

The reaction mLcure uis dJl.B.ilved in hot bea:enne, created with de-









colorzrl ne charc.-il, and ; .lo ..d '.[cr i lcration 9.7 & ('t ,1 of

col.orleIs cryarals Iwre recovered and idlri lfled as L-bcr.zyl--~;iri-

di.,,carboxyllc aJci bhyd.la:d, l ,: rip SS-96Ldec, Ir (n.jr.l) 'L00 (t1H),

1':;,' (C = 0: 750, and '09 ci.-1 (phen.'l r.mr (CLtI spectrum I.N 61

6 1.79 (n, 1, ring pr;.ton 1 97 (m, 1, ring protncri, ?.5 (dj, 1, rin

protur.), -..5 (s, 2, ;CC i, ,.64. (broad, N TI;), anr, 7 .1 (s, 5, C 1H ;

-,olIcular w ighc 191.

The 1-bt-ir: i-.-jatrldinec.Arboylic acid hdrri. de '() wva charc-

Eer li.-d S Lthe 3cc'once r.ydra.-'n 1a .



1-frh-., l---I zir L-rLrc arr bu.; ic ;.c i I hydraizd i '1.)


Metnyl i-pnrl, l-'-.-a:rtdiri ecnarbxylace (r.I 10.78 g, 0.Od nol'i

rnd h.draz;ne hydrate ('..0 5, 0.0., mol) uere 3cirrEd together at rror

c.cpor..rc :or .:..c h:.Jr. e ,zene (-.5 irl) t.a dlel aj-n re=em...s-' tI a U, -

oratirn in vjc.jo. Ecther (25 li, Las added anda j sid formed which w3s

ter n 'asned wich erner to gl.-e 5.e g (l54'.) of the aziriltrie hydramide

(Li: ; 6i.7-75) dec, zr (nujol) '12'0 (Nl'l 1 )70 (C = o) 1~6r, and t95

cmr" (phenyl); inr (CLCL,; spectrum lio Ti -. (m, rinse r.rotons ,

2.76 (dd, 1, ring procuin 4.15 (bruad, 5, :1,H7) and 7.r1i (m, 5,

C H ); r.olecular at liht 177.

Ihe I-pheryl-;-aazirLdinecarboaxlic acid hydrraide Q ) .s' chj.rac-

terized as crh acetcone hydraorone I..



1-Benzyl-_- -; iridlnecarb'ullIc Acid Hyaraztde-.creone
Hydrazone (15)


Methyl l-benzyl-2-adlridlnecarbox'ylate (1j, 1.8. g, 9.5 rmaol) and

nydra:ine hydrate (0.L78d 9.5 nmol) were stirred Eogcther and warmn-d






65

on a steam bath tor ten minutes. A u-hlte cake formed ht[ch rs then

dissolvel in acectone (10 ml'. rtEcr abour ten minutes -.2 g (70.) of

colorless crystals of the hydrazone (5) precipitated. They were re-

crystalliz1d from methanol. mp lli-1Lo, ir (nujol) 1780 (C = 0',,

l'65, (C = 14), 7;0, and 695 cm" (phenyl), nar (CDCI,; speccrurn No d)

b 1.79 (a, '., Ci ), 1.95 (m, 2-, ring protG nS), 2.04 (5, 5, CH ), 2.35

(dd, I, ring procon), 4.55 (q, 2, 0.H_), and 7.31 (s, 5, C .H ; m;lec-

ular uelght 231.

Anal. Calcd ior C H 11 0. C, C,.51, ,, 7.1l; 8, 18.17.
3j 17l
Fcund. C, 67.59; H, 7.41; N, 18.21.


l-Phenyl-?-Azirldinec rbcyylic ,ci d livdrazide-Acetcone
Hydrrzcne (Io)


l-Phenyl-2-3atridinecarbo,:)Lic acid hydrazide (., 0.1 g, 1.0 urnol.

was dissolved in acetone (7 mli at roam temperature. In about five

minutes 0.1 g (70;) of the hydrazone f(l) precipitated. It uwa re-

crystallized irom methanol. mp ll-17l40 dec, Ir (nujol) ;111 (FM)),

1690, 16i0, and l 0 cm- (C = ) and C = WI); noir (Cl: '; spectrum No 9'

E, 1.8 (5, 5, CH,), 2.09 (s, ', CH,), .51 (m, ring Froton), -.69

(dd, 1, ring proiro), and 7.1 (m, 5, C H ): molecular weight 17.

Anal. Calcd for C ,H N ;0: C, 6 .'; H, .6; ti, 19. 4.
--- l 15 3
Found: C, t'6.h9; H, 7.05, I', 19. 59.


Re ,actln of l-E-BucyL--1-.tridine cart.xylic Acid Hydr.-ide
9i% ritn afterr


Methyl l-t-bucyl-'-a.irldinecarboxylace (j, 1.57 g, l0.O umol:i and

hydrazine hydrate (0.48 g, 9.5 mmol) were stirred for nine hours at

room temperature. rhe resulting oil, crude I-r-buryl-2-azdridine-







carboxylic acid hydrazide (9 was then refilued overnight in water

(15 ml). The resulting reddish brown solution u.s cooled to room cem-

perature and concentrared. On standing overnight 0.. g (15',) of 5-t-

bucylarinoprcplonic acid (11) precipitated and was identified by com-

parison of ir and nmr spectrs and mixed melting point with an authentic

sample.

3-t-hutylsa inouprcpionic Acid i 11,,

t-Eutylamine ('.65 g, 0.05 mio) 3wa added tc. a solutiLon of acrylic

acid ().60 g, 0.05 mcl) in pyrldine (10 ml). Evolution of heat and

the lnstantaneoua foriration of a colorless solid were .baerved. Ihe

mLx.cure was then reiluxed focr three hours. The solution was allowed

to cool to room cEmperature,and the solvent was removed by rotari evap-

oration. The residue was washed with acetone to Live 5.68 g (79i; of

'-t-butylaminoproplionc acid (J)i, mp 29-2u ; ir (nujul) 3u00 (1IH),

16o0 and 1540 cm1 (C = C); nor (0,0) 6 1.64 (s, 9, E-bucyl), .Su (m,

, CH-) and _.54 (m, C, CH.); molecular weight 145.

Anal. Calcd for CH .. '0: C, 52.80; H, 10.7 ,; hl. 2,.; 9.

Found: C, 51.56; H, 10.50; N, 2 .617.



rhermal Decomposition of l-t-Butcl-=-Airldinecartoxylic
Acid hi razidJ. 91


Methyl 1-t-outyl---alrldlnecarboxylace (i, 31! g, 0.0? mol) and

hydr.zine hydrae (1.0 g, 0.02 mol) were mixed and allowed to sit at

room temperature for five days. A colorless solid precipitated which

afcer recrystallizdatom from ethanol gave O.J6 S (1'-) of l,2-dt-j-t-




This avnthesls was psccerned after the synthesis of an analogous V-
amino acld.8'






butyl smnoproplonyl l.ydra3=ne fIrl : mp 15'-l10 0 ir (nujol) 3075 (i'),

1690 and 1r'85 cm-1 (C = U'p, ni.r (D,,0) 6 1. Y. (s, 9, t-bucvl), 2.'7

(m, _, CH,), and 5.17 (m, -, Cil)., molecular weight 286

Anil. Calcd for C 14H WN u2: C. 58.71; H, 10.Sc.; N. 19.5.

Found: C, 58.81, l, 1 .12 II, 19 6.






Fragmenatricn of 1-lt-Bu.l--- -'iridirnecrDox'lic e.cid
Hyvdrazid ('sj n th? r- s=ncE of re oeenlenr


A solution of azoben=ene (0.84 g, 4.6. nmol) in methanol was added

to a solution of I-r-butyl-2-auiridinecarboxyllc ,cid hydrnzide C(, 1.5 g,

9.0 [maol) In ethanol (25 nil) at room tCemperature. The resultirng solu-

tion uas refluxed overnight. Tic (benzr.ne,'alumliin) howud disappear..ce

of azobenzene and appearance of hydra-obenzere. UWien the solution ws

concentr3Led, 0.22 g (2-I'i of crystals precipntaced and were identified

as hydrazobenzene iater washing with cyclohex3ne: op 120-14O (Lit. Ili-

1 6).87

The iltrate uas evaporLtd to a solid whlch after washing with

ether yielded 0.1 g (8'..i of 3-t-butyl.minopropionic acid i().



Therrial Decomprsition of -enl-En --.'irlidr.ec rbOx lic
A.cid HydralJde (Li In 'J.i aer



I-Fenzyl-2-azirtdinecarbo.-:,l1c acid hydrazide (L., 0.4 g, 2.0 mmal)

was dissolved in iater and refLuxed ior three hours, then cooled to room

temperacurc and extracted with ether. The uater layer was evaporated

to precipitate colorless crystals uhlch were recrystallized frcm methanol

to give 0.1 g (2c..) of 3-benzyldaninoproplonic acid (1j). This was Iden-







lified by comnirison uf ir spectra and mixed melting point ulth an

authentic simple.



-en1eri:/! nopropioonic Acid '17 8

Acrylic acid (3..6 , :.05 moli and tenzyljar.ine (5.' g, 0.05 .ol)

uwre reilux.d tn pyridine ior three hcur., tren cooled to ruco tempera-

Lure. On atandi'n, >..8 g (4-".) of :-brzylaminnopropienic acid (1),

precipicat d ITis was recrystall:ied from mrfehanol: mrp Y18--180.,

(Lit. 16-10;C' l;8M ir (nujoli 1c.0, 1570 (C = L'.,, 5.jn and TOj cm

(phenyl'i ; nmrr (D..') 2.57 (t, -, CHj), (c, , 4.51' (s, 2,

CCHMi and 7.80 (E, 3, C.H




Thernal Decoripo. tc-n oi l-Etri,. 1--Az ir tdinecicr:joxy c ic
i.cid I. Jra idi I ., in hiethair.


A soluric-n of l-ber-:/l-2-aziridinecarboxylli acid h5dra.ide (l5,

1.0 g, 5 0 anc.l was reiluxed overnight in meth.nocl (25 ri). The solu-

tton was cooled to room teaiperature and evaporated to an oil uhich on

discillatiorn ave 0.'7 (r)", ofi methyl 3-benzylam3Lncpropicne.te ( 8)

bp 90 (0.5 r-.I. An aliquor of the oil .as dissolved in anhydrcus

tther (25 mli, and dry HCI g3a was bubbled through the solution to pre-

cipitate the hydrocnloride (91 of methyl '.-ben.ylaminopropicnate.

This was ricrystallizel frcm cthanel to give cclorless needles: mp

159-lr,). Idenltiication was made by comparison of ir and nmr spectra

and mixed melting points with an authentic sample.









HMehvl -Be 6rnylai noprOconate (CI)


Ben-Ilarlmne (6.22 g, 0.058 moli was added to a solution of methyl

acr) l (5.0 8, 0.U58 moll tr methanol (50 ml, and the solutcln wv3

allowed to sit at roof temperatures ueTrnLcht. Methanol was removed by

evaporation to gi.e 11.2 g (100.) of methyl .-bnr.zylaminopropionate

(1i). Fry HC I was bubbled thrcugn a solution of 18 in anhydro,.s ether

to precipitate the hydrochloride l9i oi methyl '.-ben:ylamincpr.pituVate.

This was recrystAllized from ethanol: ap 155-1570(Lit. 155-l13 );
-I
Ir (nujol) 17.8 (C = CI), 76 and 69o cm- (phenyl); nmr (D.0) 3.21

(t. 2, CH )., }.re (t, 2, C ), .07 (. Cli), ..62 (a, 2, 'CCiH and

7.83 (s, 5, C.H); molecular weight 206.
U-a



Frroaperrq'rr r.nf i-Pren -?-P..tridiLnecarbcyic Acid HydraziJe 41'.
in the Fresence of Aoben:re -n



1-Benyl-2-azrridlnecaroxylic acid hydrazide (L., 0.39 g, 4.'.. nMic-

was added to a srclution of azobenzene (ij.25 E, 1.4 mnnl) tor mcharn l

(25 ml) and reflux-ed cr 3LX hours. Tic (beinzen;.'aluraini showed the

disappearance of c -oenzene and the appearance of hydrazonenzcne. The

solution was evaporated to an oil Thick Ijyer chromatopraphy (tben:ene

aluianal gave 0.25 g of a mixture of a:oben:ene and hydra=obenzene and

0.40 g (45'.) of ethyl 5-brnzylamrinopropion3te (. h).

The mixture of e:obcnzene and hsdrazobnzente was column chroiato-

graphed (benzene/alumina) tu give 0.035 6 (9') of hydrazobenzcne uhich

wan recryatalllzed irfrm fethanol; ap 125-1i 7 (LiL. 126-127 ).8








--Anllinopropionic r cid Hydrazide (81

l-Phenyl-2-a:iridinecarboxylic acid hydramide (C, 0.90 g, 4.7

maoll was dissolved in a solution of hydrazine hydrae (LU ml) in

ethanol (10 ri1) and refluxed for one hour. The solvent was evaporated

to give an oII. Benzene (10 ml' was added and evaporated to give 0.87

g (921) of crystalline -anilinopropicnic acid hydrazide (s). This

was rtcrystalli:ed from benzene: mp 89-900 (Lit. 95-940) ) ir

(nujol) :5 (Mi), 1,;8 (C = 0), 74 and C cmr (phenyl), nmr (D 0)

5 2.78 (t, 1, J = 7 H.! CH ), 3.72 (., 2, J = Hz, CH2), 7.4 (m, 5,

C,.' ; molecular weight 179.


lj-Diphenylaziridine (-I)

This 'asi prepared accordion co the procedure of F. J. Corey and

M. Chy!:onky 9u

1-t-Eutyl-2-h rtrdinecarbinal (22)


This wv prepared ac-ording to the procedure of C. L. Moyer.40


Ethyl Ben:ylaminoacerate

This synthesis was patterned after a procedure by Spe2iale and

Jaworaki.91 Ethyl chloroacecate (?1. g, 0.2 mol) was added drop-ise

with stirring to an ice cooled solution of criethylamrne (20.2 6, 0.2

mol) and anillnc (21.4 g, 0.2 mol) in benzene (1;0 ml). The tempera-

ture uas not allowed to exceed 50 during the addition. After addition

uas complete the reaction mLxture was stirred at room temperature for

one hour. Then potassium iodide (2.0 g) was added, and the reactLon







mlXLurt uws reilut d overnight. It wL their, allc.ed tu c:.ol L t room

rEmTi.e rt ire iand Uahed uith .cqueuus iodlum cirbonjte jnd there ujrcer.

The benzene vas remo.vd by ev-pc-riticn, .nrd the residuJl oil wus dis-

tilled to Live :'5.8 (6T' i c. h l ti bnz.EijamtroJacEEitE: bp 91l-9'

(03.- m'i (Lit. 1650 (lI mmrna!;9 it (liquid film) C..5 (Nl', 17,)
-i
(C = 0), 7410 and 701' cm- (pt.en:lI; nrnr (CCI ) 5 1., (t, 3, CH,), t.7d

(broad, 1, NH), 2'.?5 ( 2, Ci i, .T7) (s, .-, CdL 1, H .1 (4 CHSCH),

and 7.2 (s, C H.).




Beri z l ir,.cjceti,: cd ti drjzide ( .')


Ethyl b--nzylaminc.3ace.ta (' 0 ,J O', rnoli urs stirred ret vith

hy razine hydr Le (e.0 g 0.0 4 iolI). The liet.ro.eniccus mit.urE '-,'

wjrmed on j sceEj bath for three minui;r then oEirred t ,rbier, teri-

pcriLr* fu[ r u e I.~u. a the iC ture Lec.-Me hc.rGc cn.:;u- .. :cd .a:

udJed apd a cc-lorless cake formre. lhe cake uws recrystall:ed ir.oi

isopropanol to give '...'? (r5r) ot bcn:yvlaminAcectic -cid hydra:t le

_(. : mp 0-)-sic (Lit je-8"', itr (nujol '.- 5 (:jhj, Itc' (C = Lt ,

745 and 7)u cin (ph=r.nyl,, nmr (Cl:I, = '.. (trcu d, ,, ), 1 .',

(i 2, CH I. .72 (s CH and T..9 (is, 5, C .H molecular ueig-.t

159.


Antlincicettic cid Hidrazide fi41


Hydr:jne hydrjte (4.0 A, 11.03 mal w3 j3-ded to si-luctin rf

ethyl anll inocetnce ( .58 5, S).0.Z mol' rhe mixture formed a solid

cake within a iew minutes. Ethanol (.20 mli' ws added, ird the mixture

was refluxed fir cto hours. Colorle.s plice, precipic.ritd on cooling.

They vere recryetallized Lrom cthajno to give 2.95 g (89.1 anilinu.







So 94
acetic clid hy-rizide ( .'j; mp 125-i2L 5. (Lic. l2o. 9), ir (nujol)
-l
3;80o (I:H), 16i (C = 0) -1i and 6 i5 cm (phenyll, nar (DO() 6 4.0r9

(s, 2 H, CH), and .:. (m, 5, C H.).




1.--Dipr.n, 1 3z r Ia Ini ( _1)- ca tD i Ir.y co ii',drazine Hydrate


l, -Dlphenylazrtldine (21, 0.95 g, 5.0 nmol and hydJrd:ne hydrate

(0.04 g, 7.0 mTil) Vere rixed together With Fnough methanol (4 ml) to

eifect scluticn. The solutLcn wus Iett At room tempcraturc for four

days. 'olvenc was removed bL evajpportion. An nur spectrum of the

residue indLcaicd that no rejccicn hl occurrel.




I- c-Futyl-- zLridinec rblinol (D' I-Stability t.o IIdrazinp Hvdratp



hyrazilne hydrate (0.Il &, 15.0 iiimoll ws idded to I-t-oyuti-c-

aalridlnecarbancl C, 0.96 g, 7.5 rn0ol and enough methanol to effect

solultor. The solution was left jt rocm temperature tot lour dajs.

SolIent was rEmoved by c\aporJ on. en nrar spectrum of the residue

tndictLcd rtht no reaction had occurred.




Benr ylamin acetic rcld Hvdra:ide (!l)-'Stabli y to Metlhcanol


BenzlamI anoacetic acid hydrazide (., 0.57 2, ..2 rmol) uss re-

flum.e in nIechJrol (25 ull for .4 hours. tic (chcloroicrm-uecthanoll

alumina) indicated that no reaction had taker place. Solvent uas re-

mosed b. evaroracion. The resldual oil was taken up in e-propanol,

and the resulting solution, vh.n seeded, yielded 0.51, 5 (95'.) of .':

mp 80- 8c.









Antlinoa.-etic Pld Hydr.vilde (24).-'cabili, to Methanol


Antllnoacetic icid hvdrazlde C 0.54 g, '..;7 imuli uas reLluxed

In methanol (25 ml) for 2- hours. Iic (chloroform.'aluninaj) indicated

h.ic no reaction had occurred. *:-lv-enr wa3 reumoed by evaporation to

give 0.S.9 g, (100.) of d4: mp 14-1c6..



Lthyl . -f etr 3methyleeglyc idaLe

In a flame dried apparatus etchl chlor~icencae (1. 8E, 0.1 mol),

cyclupentanone (8.1, E, u.1 mol), and dry dilITr.ie (50 fi:) -ere arirred

at ice-s.lc tenreracures. Ptc.assium -buLoice (11.0. g, 0.1 mol) was

added over a pertid of l.,5 hours and the resulcint mixture Jas

stirred at Eha3 temperJture for [cw h.ur3, then at rcairi temperature for

five hours. Hydrocriloic acid (c.:Jl was added until the solution was

slightly acidic (yellow to pH papri and solids were removu.d b centri-

fuaJLion and tillraCton and uashcd with etpcr. Solvent uas rerr'moed

from the iiltrate by evaporation to ive a dark oil shich on disctlla-

tlon gave 7.84 r (hoaj of ethyl r, e-treramethylenet.lycid;te. np d0-2',o

(Z-) mm) [Lit. 90-95c. (- in)]; 9o Lr (liquid film) ;U3o (CH) and 1750
-1
cm-1 (C = 0; nmr (CC1 ) 5 1.29 (c., CH,), 1.7b [broad m, (Ch ) 1'

3.55 (e, I, iH' and 4.18 (q, 2, CHL CLJ. The nmr speccruim, also con-

cained slnals indicative of some E-butyl eT. B-tetramechyleneglyi;date

as a major impurity.


* Ihts procedure was patterned after a similar synthesis by U. V. Moycr.











I.,-TEramc thy lenc -1-rvdr o,.-3-Pjrazo Io idcne23


Hydrazlin, hydrate (u.29 4, 5.Q r.mnol) wa added to etchl 6, t8-

Eccr, eth: lene.Al:,,cidace (l.t g, 5. rmol) and the resultanr mLix ure

uas warmnd oi i stea bach for 20 minutes. On cooling to room tempera-

lure 0.-1 (.~8 f A.t -tE ram Ehy Lena -.-hydi ::y-5-pyrazolidi.ne prc-

cipiatcd. Ihis was rEcr'yicalli:ed from Ethranl: mp 181-lt8i (L.L.

1 4-185") It (nujoli 1685 cm 1 (C = 0C ;, nr (D..01 2.1' [broad

m,., (CH ) 4 aid L.7 (*, 1, CH), molecular ueirht 155.




3odfum and Litnium 1-t-Buryl-'-.zaridinec.rboxl_.cc '(5 ajnd i


Sodium and lithium 1-t-buryl-2-arzridinecarboxylajlc ij-. and 9'.

were prepared uc.-c-rding c. pricedurea parcerned aiter choFe oF C. L.

MHyer.40

Mechyl I- -butyl--=-aziridinecartbos:xlate (5, 10 g 0.0. O .4 mc) and

scdium hydr.xide (2.0. g, O.0u1 moli) veie stirred in uiter (25 mli at

rcom terperatur' ov.ernig&h. The resulting clear solution vaa then

wished rice wirh chlorrtorm (20 ml) and evaporated cu a tine powder.

The powudr was dried undcr vacuum to give 8.14 g (':61) of the sodium

salt () which his identified by spectral prc-perEies.

Lithium 1-t-butyl---aziridinecarb-'.-y.13CE (4j) 3as prepared in an

analogous manner (14..u e, 94*.1 irdim ILL ium hdroxide ( no rydrate

(4.2F p, 0.1 mol) and I-c-buc.l-2-azirldinecarb.xvylatE (1L.? g. 0.1 mol.










SLaCLrm C -1 -[-5iUL, -'-- rerh.Il- --. r.iridLcci jrhc,.. l.c *:7


MeNchl C i- 1- c-t ue-. .-mi h l-c- zirid1 nccarbola ( 7 ,

'. j in, l Wa a ;t irrid cvernright at roora tcLmpetraure 6ich sodium

h/dro:
ia, -rned with chILrLic.rLrm nd J .',pcraced c:. 7 g.'4 0 i99.1 of chr ;Aui1r.i

Sail t ): tr (nuj ll i IL.,)i ( C. ; ni) ar 'l m .O speccrum rio ,) 5 1. ..i

( c-butyl, 1.' (1, CHi : .48 (m, 1, ,H dand :.."t (1, 1,

C. FL).




Scdiun T nrJan -i-t-But, --Me tr.vl--'- :[ r .inec =rc.xyl ac i~; l


lthclL traj.s-1 t-bucvl- nchyl-- j: r idinc.arboxyl ar3 C L. u ,

7.'- r-r,l' -nd ..,di., nh-IdrL ide (0t'. g- 8 .0 mru a il were stirred tL eLti.er

in v Lwa r (15 ml) L room te perp care. a ..crnLn'r.c. T-- rsu. lti n .. lucict

'.,s e.'poratLed Lt 1.1,9 p (9. ) ort ch-e s dur, sale (1 .. : Ir (nuj l) Ilr. 1
-k
and 15v'0 D (Cu. i ; nr (D.u; spectrum Nc l,. 5 1.!5 (s, 9, c-but.l),

1.48 (d, ;, J = c. Hz, CH,p and ..il (ia, ring proccnai .



Triah nrvil 1 i.L' 1-fi - I- l- ztri dinecarb.a.lace (cI11


Sodium I-c-but.' -e-aziridinEcarbcx,/ljAcc ,. 8.0 ., 0.''.8 -:-l. i

wa; added toi bcrnscn (.4-j) ml and th r i ome n rozcne (25 mEl' La re-

m:.ved by di3Eillatl Cc. rer.iae water. SULd Erirhenylmuehvl bra:mid.:

(8.u E, 0.'ja8 U:ali 'c .* added Ajlnc with enough bnzennre C, miiak. Lhe

tctal volume abcur 2'1jJ ml. The resulting alurry Eas stirred rapidly' .

it a rciflax for l1 hours, then cl.."ed cc room. terperaLure. Colids Wa-.re








removed by filtration through filter cell and washed wlth benzene. The

filtrate was evaporated to an oil which waj treated with hexanes (15 ml)

and Fliced in a refrlcerator to precipitate 5.? g (5'.) of triphenyl-

methyl 1-c-butyl--aziridinecarboxyltce (1). Repeated recrystalit:a-

tlons from hexanes give a pure product: mp 117-1193, ir (nujol) 1730

(C 0), 790 .nd 710 cm-" (phEnyl); nmr (CI 4; spectrum No 10) 5 0.95

(s, 9, t-butyl), 1.59 (dd, 1, ring proton), 1.92 (dd, I, ring proton),

2.12 (dd, 1, ring proton, and 7.10 (m, 15, rfiphenylmechyl); molec-

ular weight ',85.

Anal. CalJe for IH. lO.: C 1.001 ;.0a; I1, 3.;.

Found: C, 81.Ou; H, ".1l ; N, 3.62.



Pyrolyeis of Tripeen-lmirth; 1-t-Butyl-5-Azlrldine-
carbo'Iylate 19L) in En:ene


Benzene (10 ml) 'as added to Lrtphenylmethyl l-t-butyl---a:Lridine-

csrbc.xylate (1, 0.40 g, 1.0 rinmol) in a thick-walled glass tube (25 cm x

1.5 cm). The tube was flushed with dry nitrogen, cooked in a dry Ice-

acetone slush, sealed, and placed in an oven (175-1O0 ) for 14 hours.

When the tube was again cooled in a dry ice-acetone slush and opened,

considerable pressure was released. After concentrating the contents

of the tube to an oil, the reaction mixture was column chromatograpned

(10% alumina, 1.0 cm x 30 cm, 0 g) using cyclohexane as the eluent.

Two components were isolated and characterized.

The iirat component to come off the column was 0.o1 & (145'.) of

l-t-butyl-2-trlphenylrit hyla:ridine (.5). this was recrystallized

from ethanol: mp 114-1150; ir (nujol) 1.25 and 14.'0 cm- (phenyl);

nmr (CD 1 ; spectrum lo 11) 5 0.3 (s, 9, E-butyl), 1.02 (dd, 1, ring







proton), .1.' (d..!, I, rin. prcton 2. 40 (dd, 1, rln proton), and

7.2 (road a, Li, rriphenylmernyl), MOolecular weight .1

Anal. Calcd far C H ti C, 87.93, H, 7.97, N, .10.
FounJ. C, 37.98; H, 8.09., t, 4.00.

The .econ.i copnenant to come off the cclurrn ua. 0.08 g (..) i.f a

colorlie.s solid characrerl.ed is '-b-Oityl-cr ph..,ylmethylImch.,lamwne

(,_) This .as recr;sct.l itzed from ethancl: mp li.id-109c; ir ('.Br'

Oiuu ( 7l:), 7.I and 699 cr- (phenyl); nmr (CC1 ) 1:.;.6 (broad, 1,

NH;, 1.04 (s, 9, E-butvl), 3j.5 (- , C, U.), and 7.19 (s, 15, crl-

phenyrlmichyl), m'lhcular weiphc 5;0.

Anal. CalcJ fcr C H .a 1 C, 8 7.4h9, ,8 2.; r,, 4. 25

Found: C, 37. :; , S3. I, N, 4 :0.



'Therml T.cn,:orl pcs tl-n c. i Tr iprenl- mir,1l -r-Bityl-
I-.' lT i i-.ca Crtu,,yl ... i,'-li 1 ., u-:ir.e


Cuirrne usa puritcld according rt the procedure cf U V Moyer.9

rrlphenylmethyl 1-t-buty.-2-ja; ridinecarboxylatC (91, ') 4; e, 1.17

mmoi) -as dissolved in cumEne (6 mlj In a thick called jl&ss tube

fitted uith a grcird lasi jotr. The solution was dEgsc.cd by alcer-

r.acely freezing and rhawing the .olarion under vacuum (0.05 mm). The

tubL was sealed in vacuo and placed In in o.en (180 + 10c') for 16

hours. The cjuD w a then cooled and opened, and the conentns .arjli-ned.

CiG chrr.omcoiraphy (SE-;,i, 5 fr. x 0.12 La 2;Sc') ahouGd no

trace rf dlcurcyl. By c-amination of standard solutions it uas estims-

red that j.2. of the theoretical amount of dicumyl could be dc-cted.

The solution was then evaporated to a crude oil. NiLr oblservation

showed the reaction mixture to be essentially identical to the reaction








In benzene. It was estimated chat 1-t-bucyl--tcriphenylmethylaziridine

(5) comprlsei 5"i. of the reaction products and N-t-but)l-crtphenyl-

metrylmechylamine 9i5 ;'.. By cclumn chromaLography 0 g (51') of

the airLdine C95) and 0.05 g (1',) of the amine were recovered.



Pyrolysis of Trir-h-nylmrn etrl 1I-c-.utyl-_-.;irtidinearbc.xv-
li.t (u11 i c. nzene in the Fremence of C-b.-canol


TrLphenylmechyl 1-t-buryl-2-32LJdinecarboylace (1 0.45 g,

1.1I mmaol), t-butanol (0.06 g, I 17 mmiol), and benzenc (8 ml) were

placed in a glj3a tube. Dry nitr.gen was bubbled through the solution,

and the Ltue was sealed after cooling in a dry ice-acetone slush. The

tube was then placed in ar. oven (I.i +* 10c) for ten hours, cooled,

and opened. The contents of the tube smelled faintly of formaldehyde.

The benzene solution was washed uwih water. The water wash gave a

positive color test with Fucnsin-aldehyde reagent. W1 hen created

ulth aqueous dimedone reagent a colorless solid precipitatEd which was

recrystallized from ethanol-water to give colorless needles: mp

188-18a9 (Lit formaldehyle-dtmedone derivative: 1890). 98

The Den2Ene layer was dried (Mg-04 ) and evaporated to O.Li. g of

an oil. The nmr spectrum indicated that the oil consisted of 1-c-

bucyl-2-criphenylmethyl.ztridine (95, l1.) and N-c-butyl-trtphenyl-

metnylmethylamine (, 88'.). The oil was recrystallized front echanol

to give the A.7 g (50. of the amine .): mp 105-1070.



Thermal Scability of l-c-But..l-_-Trrlphenylmrethylazirldine (95i


The azirldine (95, 0.05 g) usw disso,.ed in benzene and placed

in a thick-walled glass tube. Nitrogen was bubbled through the solu-





79

Licn, and the tube ujW Looled in a dry cce-acetcne :Lush and sealed. it

wai placed In an cv.'en (180 + l0li for 14 hours, ccrlca, and opened. Tic

(cyc lohe.i nc /lumina.i ahc-ed crnl. cne spot due t~ the sc rErins azi dine

The ben:ene .i-s evapcraced leaving a cle-n oi1, -nd rl rL otbgervajton o

the oil showuej onl, clejn scarcing a=irzdire. he- oil '.s recry' allied

from echdnol to ELve 0.53 g (7.-1 of the a:irl line (L .




Pyrolysis of Tr ipher,.'l-ethyl 1- -?utC-'- -rldine-
carboulare 3 'Ii in I'echjnoi



nitrogen uas bubtlied rrouen a slluticr rp otcripnylmEetnyl

l-c-buryl- -a irtLJr necai b, lace (L 0.-0 ;, I.!. mol' inr erchancIr

(5 ml) in a glass tube. Tlhe tune wjs sealed (-7Ti0) and placed in .n

oven (120 + 1u) for 14 hours. The solution turned Drr''n. (Cn ccolinr

0.--' g (75'.) 2i mecChy! triphen..-l chyl el her prici.i: Cd. It wa-

idEnclfed bty comparison to .an aurhcnr.i sample

The filtrate show,-d no moving spoec orn ic (beri:ene/aluminia. r.r

nmmr spectrum of the recidlal oil left jtier evaporationr ci the solvent

should no recognizanle sienals.



Methyl TriFhenylnethyl Ether


ThLi uas prepared by 3 procedure patterned aiter th't ci Ilcrris

and Young.99

rriphcn) lechyl branide (T. si. 0.01 mcl' and sodJi-m methcxidc

(0.54 g, 0.01 moli uere refluxed in mechanol for cer. hKiur. On ccrcline

2.2o g (8Z') of methyl criphenylmethyl echer precipitated. Thli 'as re-

crystallized from mechancl* mp 80-81).5 (Lit. S2.6-92.9.199











Reaction of Lithium i-t-Hucyl-2-AztridintcarboxylatE (49)
with Thtonyl Chloride

A sodium hydride suspension (0.96 g, 20.1) mmol), washed three

Limes ulih cyclohexane, uas dded to ceLrahydrcfarari (25 ml) under

nlcEognr to form a slurry. Lithium l-t-bucyl--2-aziridinearbcvxylate

(4, 1.0 g, 6.7 moL) 0 as added to the slurry followed b) dropulse

addition of thlonyl chloride (1.19 g, 1.fJ mnc-l). The resulting

mixture was stirred at room temperature for 1.25 hours. Solvency was

removed by evaporacion,3nd cyclohexane (75 ml) uas added followed by

careful addiilon of water to destroy the sodium hydride present.

The organic layer was separated and iashcd with water, dried (Mg504),

and, after evaporation of the solvent, distilled to give 0.25 g (2..)

of I-t-buLyl-;-chloro-i-a.etidinone (0): bp 700 (0.. mm); ir (liquid

fllm) 1760 (C = 0), 814, 745, and 695 cm" (C-C1;, nmr (CC 4; spectrum

No 12) 5 1. 5 (s, 9, E-b:tyl) 3.18 (dd, I, CH), ..78 (dd, 1, CYH and

4.57 (dd, 1, Ci) ; molecular weight 161, 1L..

Anal. Calcd for CljllLt-Cl: C, 52.01; 11, 7.43; N, 8.67.

Found: C, 52.27, H, 7.65; N, 8.46.

Slightly improved yields could be obtained by removing excess

sodium hydride and salts by filtration followed by distilladton of the

residual oil: 33..








Reaction of -odium l-t-bucrl-2-- -trl. inecarboxvl re (5S)
wulh .,i.alyl Crloridt*


Solid sodium 1 --butyl-2-oziridinecarboK3lace (,, 1.05 g, &.

mmol) was added to a solution of oxalfl chloride (0.95 7.* mmol) in

benzene (10 il) at room tLmperature. Both holL and gas were evolved.

The resulting slurry usa refluxed for 15 minutes. Benzene (Su ml, was

added, and the alurr' was ujahed uith aquious sodium carbcntce, water,

and dried (MSO, I. DistLllacon of the residual oil left after Evap-

oration uo the solvent gave 0.2?c6 g (2'.) of 1-c-butyl->-chloro-'-

azecidinone (,.m). Tnis was identified by apictral comparl6or. to an

authentic sample: bp 900 (0.7 mi).

Reaction oi Scdiud l1-[-.utyl--izlridinLcarbc.sylate (5f'
with Oxalyl inloride in the Presence .f Trlirrhylamine


The sodium salt (j, 1.05 g. 6. mmol) wua slouly added to 3 mLAture

of uxAlyl chloride (0. 5 g, 7.5 mmol and criethylamine (O. 6 g, 7.5 rmol)

in benzene (50 ml). The dark brc.un slurry w3a stirred at room cempers-

cure fur c-ne hour, washed with 5'. HiI, sodium carbonate, and jwaer,

dried (?LSuq '1, and evaporated to 0. .j g( .of L--butyl-.-chlc.o-;2-

a:ecldlnone (.l) This was identified by comparison to an authent i

sample.

Reaction of SodluJ Cis-1-=-Buu"l-'-=Heth l-=-=Air idinccrboxyla e
(67) with COalyl C hlcride


The odium salt (7, 3.1 p, 0.019 mcll 'wa added slowly to a




* This reaction uas patterned after a general synthesis cf acid chlcrides.







solution of oxalyl chloride ('.0 g, 0.025.' mol) Ln benzree (0 ml).

The retultlng slurry uws SLtired t ambient temperature ror one hour,

and then a few chif- of ice were added. Benzene (C0 m'l uws added, jnd

the reaction mixture was washed wich sodium carDonate and water, drid

Q(1850 ), -an evaiprated to g.. (96.) of a clean oil which w3s dis-

tilled to ;l.e 2.o g (79'.) of cis-l-t-butvl-5-cnloro-4-nethyl-2-3LetL-

dinonri (9 : bp r.5' (0.1 ms~ ; ir (liquid film) 29.0 (CH), 175T c-1

(C = 0), rmar (CCI1; sp.ctErum No l 15) 1. 5 (s, 9, t-bucyli, 1..O

(d, 3, J = 6.4 Rz, CII 4.01 (m, 1, C(1 ), and 4.10 (d, 1, J = 5.1 Hr,

CGCO), molecular -eight 175, 177.

The cil usa reditllled for an analytLcal samble, but even ,hen

stored under 3 vacuum it jwa unstable at room Lemperature. rTus it

is not surprrning thit the arnalytical sample did n t check.

Anal. Calcd for C H IliNil: C, 54.c,; H, 8 05; N, 7.9d.

Found: C, 5 i'. H, .9 ; Id, 6.02.



Feacrlon of Sodiun Trarn.-l-t-Eutl-'.--nthyl_-.-r'.iridinecarboxl rte irP
-- attIn Ualyl CI uride -


A mixture composed of sodium trana-l-t-bucyl-j.-methyl-;-a3.iridi.e-

carboxylate (. I.. g, ..0 mmo'l) and an Inert salr was added slowly to

a solution of oxalyl chlorrie (1.09 g, 8.7 imr.l) in benzene (25 ml).

The resulting slurry -'as stirred at room Lemperature for one hour,

uwshed uith 5'. HC1, aqueus sudiuo carbonate, and water, and dried

(MgSO ). The solution uas evaporated to 0..5 g (6.5.) of trans-l-t-

butyl-3-chlnro-4-mechyl-2-azetidinone (7,). The oil was distilled for

an analytical simple: bp 650 (0.1 ms); ir (liquid film) 29',0 ((CH) and

1751 cm-1 (C = 0); nmr (CC1 spectrum No 18) 6 1.34 (s, 9, r-butyl),







1.45 (d, ', J = 6.1 H CH,), ,3.6 (m, 1, CRN), and f '.09 (d, 1,

J = 1.7 Hz, CHCO.; molecular weitht 175, 177.

Anal. Cjlcd for C H 14r'( 1: C, 54.b6; H, 6.05, 14, 7.98.

Found: C, 5..79; H, 7.91; N, 7.87.



Ring Expansion cf podium 1-t-Eutyl-'.-i:1ridinEcrrho:yl jte (5'.)
with :.cs,l Chlorji in ..cecon trLle

The sodium salt (.7, 0.77 t, 4.7 mol) and nosyl chloride (1.02 g,

lI.'' M lol) uwre stirred together In benzene (50 ml) for four hours 3C

room temperature. The slurry was washed uith water, dried (MHE'. ), and

e.'vporatcd to an oil which consisted of a .imture of nosyl chloride

and I-t-butyl-2-azlridinccarboxyllc acid anhydride ( (7; spectru No

20). The oil was takcn up in 3 solution of retraethrl armoniuum chloride

(2.68 g, 16.0 mnnol) in acE:onitrile and left at room temperature over-

night. The resulting orange solution was evaporated to an oil, Laker,

up in petroleum ether (bp -7-id0), washed with water, dried (Hgc3 ),

and evaporated to a pale yellow oil (0.2S0 g) which was shawc, by runr

spccrroscopy to consi;s of 1. g (17.) of 1-L-butyl-.-chloro-2-a'lidli-

nonc (S) together ulth ;s3me extraneous material.



Ring Fxpanaton ot SOlitum Ci '-1-c-buc'yl --hsct hyl-A-.Azridine-
carboxylace lu's7i .th ic.:ayl Chlorid: n ,ceconisrile


The sodium salt (Q, 0.17 g, 2.0 mrol) and novyl chloride (?.4' g,

2.0 ncnol) were stirrod together in benzene (50 ml) for four hours at room

temperature. The slurry was waahed with water, triedd (ht50, ) and

evaporated to an oil. The oil was dissolved In a solution of LeLra-

erhyl aLmnonium chloride (0._; g, 2.0 mmcl) and left at room temperature







overnight. ceetonltrile was removed by evaporatiji and the residual

oil wa; taer,. up in petroleum cther (bp 5T-Lf wasnrd with water,

dried (Mfg0 ', an,; i-.-porated to 0.274 g (75 ) of an oil ilcnritied as

ciL- 1-t-Dutyl-;-C hlro-h-mrethyl---a2- tidinone i D stillation

(:5'o, 0.1 n., gave 0.IT g (50".) of the pure product.



Reaction of .odiJw C -l -r.-Bu: 1l-*.--: thyl-2-.. iridirn: rbor wuth "rsy'l Cr-lride



The .olium1 ralt (7., 0.5 g, 2.9 r~ol) and nonyl chloride (r0 4 g,

.9 csnol) ,e-re stirred it room temperatur- in benzrne (50 ml) for 4.5

hours. The resulting slurr) was washed wi[h aclUeous sodium carlh.nate

and wuter, Jried l,.ic )., and evapc.ra .d to an u.I consisting crd a
4.
miKture ot ci-l1-c-butL I--m;rChyl-'-a:iridinecrbh-..yllc antlydr:* I (Ib)

and rosyi cr,lorde. N5osyl chloride ('.l1. g was r'nived by several

crystallLZticr-ncr ror. petroleurm Eher The arhdrrJe ( 'L was obtained

free of nos l sF-ecc by: eveporat on of the solvent from the moCthr

liquor to give 0.-1+ S (5Is.) as an oil.



C i-1-t -Butyl-'-I- chll- -- i r i.dincc bor I ic r, nh',drlde (75)


-.tdium cri-l-t-bucyl-'.-mechyl-2-azLr ainecarbo:ylat e ( 1.0 g,

5.a maiol) and nasyl chloride (0.r2 g, 2.8 mnnolj '-re stirred together in

benz ne at room tcerpriraure for ..5 hours. The rEsultln6 slurry wa,

washed uith water, aqueous sodium carbonate, and again with uater,

dried (MgCO ), and evaporated to 0.o J g (76.) of an oil identified as

cis-l-t-bucyl-5-.merihyl-2-aziridlrecarbcxyltc annydrtJe i _b). The oil

was taken up in pecroleurns ether (bp .7-1 ) and filtered to rtraove a

fine insolJble suspension. Evaporation of the ilrLcrtc gave 0.57'-







(69.) of te anhydrld- (T:i) as in oily 3olid! ir (liquid tluAl 39;I..i

(ll)), 16.'0, i )00, and 1 'LO ,Cr,,I (C = .' r.tnr (CC1 ; spectrum u lo a 211

5 l.'j (s, 9, r-buEyli 1.-26 (broad d, 3, Ch ., and 2.15 (mr, _, rin

proco n .



Reaction of Cj -1- -P.jc I-'-%. ch%-l- -..:Irl in -arLb.-:, Ic inh. Jride (75)
uih Sd-:-iuun Mc lthoi de In 1 'ear anci l In ch., Freen. or 'os .l Chli.riJ-


SLdium c is-l--bu ll-'-meie chyl-2-zir r dinec r boxy la r, ., 0. -1L g,

2.0' nnillI) nd rics>l chloride (O.kth L, .i "ii ,moi) irs s tirred ja reomt

lermierfcure in benzene, wahej Litch watcr, drlcd (llt;0 ) nd evaporjled

co an oil compos.c of the anh)ydride (.'i adnd niyl chloride. T-E c Il

uas dissolve, in a solu tcn of sodium methcxtid (0. 10 , 1 8 Pac.l) in

mechanul jnd left at room cermper.rure ovcrnishc. In.: resulting solu-

clon 4wa pourEi into benen.en jd washEd itch Uatcr. T',F benzene lav:r

,.as di;.ed (:i; ;4: an, d e.aporn.*c toi an .al.; solid. ., resl. 1 -as

taken up in chloroforrm and the -olias cere rErioved by tiltr.-[ion Tnh

chlroicrm s.lulton us, ejrapur.r ed L: O.ll1 (. .5,) ot n oil identi-

fied 3. mM th l ci__ -l-E-bhur.l-,-rechyl-i-,ziridlinec.,rtox:late ( 15i by

spectroacopy.

The ace r 1,er -aa e~ por..tcd to a slild which uws identified a

d mLxture. of sodium nosylarte ,nd sodium cias-l--bucrl-3-mn thyl-2-.zlrt-

dlnecirbo.:yl.ae (j.i by nm:a spectrcscopy.



Reaction ort odium Truan I- --u I- '-le ryl-2-, tridlin -
carbcry late 1,'. 1 *'Ln [1loyl Chloride


sodium trans-l-t-rucyl-j.--ethyl---aziridinecarboxylate (C., O g

1.7 m-al) and nosyl chloride (o..588 b, 1.7 mmrol) were stirred in benzene






at rooe tc aperiture for four hours. The resultLin slurry ujs Liahed

uith aqueous sodium c.rbonite and water, dried (MeSC4. and eaporated

to an cil (0.'.8 al consisting ci a mixture of trans-l-L-butyl- .-methyl-

2-air idlnecarboxylic anhydride (i.c and unreacced nosyl chloride:

nor (CC14, spectrum I. 30) c 1.17 (s, 9, t-butyl), 1.42 (m, ., CH~),

2.)) (d. 1, C )i, ind P.30 (m, 1, C H'.



Nmr oi the .nhydrides in Sulfur Di.I-tde


The onhydrldea were dlasol'ed in liquid sulfur dioxide at -100

and transferred in a laboratory atmCosphere to nmr 3uample tubes wuhch

were sealed. =nciples vt the anhydrides uvch nosyl or to5yl chloride

present were prepared by treacinS the appropriatE sodium sajlt with

equ.imolar amounts of the arylsuli~nyi chlorides and disslving the

reiadual oil left after the usual workup in sulfur dioxide as above.

The same spectra could be obtained by adding the arylaulon'l chlorides

to solutions of the anhydride in aulfur Jlouide, but this was found to

be less convenient.

The chemical hlrt for thie ionized and unlonited anhydrides are

reported with refirence to external cetraLethylsillne in carbon

tetrachloride and are cabulated in Tables IV and V.

Tre sc.lution of the cis anhydride in the presence of nosyl chloride

or tosyl cnlioride (after ionization had occurred) uWs quenched by pour-

ing the sulfur die.ide solution into a solutcicn of cecrsethyl sli~Dnium

chloride In ace ronitrile. Pfter the usual workup cis-l-t-buryl->-

chloro-4-methyl-2-azetidinc.ne wus reco\erd in trelds of 1I,. and 14'l

respect uely.




Full Text
xml version 1.0 encoding UTF-8 standalone no
fcla fda yes
dl
!-- Chemistry of aziridines ( Book ) --
METS:mets OBJID UF00097753_00001
xmlns:METS http:www.loc.govMETS
xmlns:mods http:www.loc.govmodsv3
xmlns:xlink http:www.w3.org1999xlink
xmlns:xsi http:www.w3.org2001XMLSchema-instance
xmlns:daitss http:www.fcla.edudlsmddaitss
xmlns:sobekcm http:digital.uflib.ufl.edumetadatasobekcm
xsi:schemaLocation
http:www.loc.govstandardsmetsmets.xsd
http:www.loc.govmodsv3mods-3-3.xsd
http:www.fcla.edudlsmddaitssdaitss.xsd
http:digital.uflib.ufl.edumetadatasobekcmsobekcm.xsd
METS:metsHdr CREATEDATE 2010-09-20T08:57:27Z ID LASTMODDATE 2010-02-04T00:00:00Z RECORDSTATUS NEW
METS:agent ROLE CREATOR TYPE ORGANIZATION
METS:name UF
METS:note server=TC
projects=
OTHERTYPE SOFTWARE OTHER
Go UFDC - FDA Preparation Tool
INDIVIDUAL
UFAD\mariner1
METS:dmdSec DMD1
METS:mdWrap MDTYPE MODS MIMETYPE textxml LABEL Metadata
METS:xmlData
mods:mods
mods:genre authority marcgt bibliography
non-fiction
mods:identifier type AlephBibNum 000955739
OCLC 16992044
NOTIS AER8368
mods:language
mods:languageTerm text English
code iso639-2b eng
mods:location
mods:physicalLocation University of Florida
UF
mods:name personal
mods:namePart Clough, Stuart Chandler
given Stuart Chandler
family Clough
date 1943-
mods:role
mods:roleTerm Main Entity
mods:note thesis Thesis--University of Florida, 1969.
bibliography Bibliography: leaves 108-113.
additional physical form Also available on World Wide Web
Manuscript copy.
Vita.
mods:originInfo
mods:place
mods:placeTerm marccountry xx
mods:dateIssued marc 1969
point start 1969
mods:copyrightDate 1969
mods:recordInfo
mods:recordIdentifier source ufdc UF00097753_00001
mods:recordCreationDate 871117
mods:recordOrigin Imported from (ALEPH)000955739
mods:recordContentSource University of Florida
marcorg FUG
mods:languageOfCataloging
English
eng
mods:relatedItem original
mods:physicalDescription
mods:extent xiv, 114 leaves. : illus. ; 28 cm.
mods:subject SUBJ650_1 lcsh
mods:topic Aziridine
SUBJ690_1
Chemistry thesis Ph. D
SUBJ690_2
Dissertations, Academic
Chemistry
mods:geographic UF
mods:titleInfo
mods:title Chemistry of aziridines
mods:typeOfResource text
DMD2
OTHERMDTYPE SobekCM Custom
sobekcm:procParam
sobekcm:Collection.Primary UFIR
sobekcm:Collection.Alternate VENDORIA
sobekcm:SubCollection UFETD
sobekcm:MainThumbnail chemistryofaziri00clourich_Page_001thm.jpg
sobekcm:Download
sobekcm:fptr FILEID UR2
sobekcm:EncodingLevel I
sobekcm:bibDesc
sobekcm:BibID UF00097753
sobekcm:VID 00001
sobekcm:Source
sobekcm:statement UF University of Florida
sobekcm:Type Book
sobekcm:SortDate -1
METS:amdSec
METS:digiprovMD AMD_DAITSS
DAITSS
daitss:daitss
daitss:AGREEMENT_INFO ACCOUNT PROJECT UFDC
METS:fileSec
METS:fileGrp USE reference
METS:file GROUPID G1 J1 imagejpeg SIZE 92060
METS:FLocat LOCTYPE OTHERLOCTYPE SYSTEM xlink:href chemistryofaziri00clourich_Page_001.jpg
G2 J2 56897
chemistryofaziri00clourich_Page_002.jpg
G3 J3 144746
chemistryofaziri00clourich_Page_003.jpg
G4 J4 202408
chemistryofaziri00clourich_Page_004.jpg
G5 J5 236641
chemistryofaziri00clourich_Page_005.jpg
G6 J6 212145
chemistryofaziri00clourich_Page_006.jpg
G7 J7 204600
chemistryofaziri00clourich_Page_007.jpg
G8 J8 202516
chemistryofaziri00clourich_Page_008.jpg
G9 J9 176681
chemistryofaziri00clourich_Page_009.jpg
G10 J10 170506
chemistryofaziri00clourich_Page_010.jpg
G11 J11 136448
chemistryofaziri00clourich_Page_011.jpg
G12 J12 147247
chemistryofaziri00clourich_Page_012.jpg
G13 J13 225600
chemistryofaziri00clourich_Page_013.jpg
G14 J14 80925
chemistryofaziri00clourich_Page_014.jpg
G15 J15 270767
chemistryofaziri00clourich_Page_015.jpg
G16 J16 270892
chemistryofaziri00clourich_Page_016.jpg
G17 J17 259258
chemistryofaziri00clourich_Page_017.jpg
G18 J18 238793
chemistryofaziri00clourich_Page_018.jpg
G19 J19 154838
chemistryofaziri00clourich_Page_019.jpg
G20 J20 163055
chemistryofaziri00clourich_Page_020.jpg
G21 J21 157843
chemistryofaziri00clourich_Page_021.jpg
G22 J22 236699
chemistryofaziri00clourich_Page_022.jpg
G23 J23 186447
chemistryofaziri00clourich_Page_023.jpg
G24 J24 180628
chemistryofaziri00clourich_Page_024.jpg
G25 J25 161624
chemistryofaziri00clourich_Page_025.jpg
G26 J26 212962
chemistryofaziri00clourich_Page_026.jpg
G27 J27 240079
chemistryofaziri00clourich_Page_027.jpg
G28 J28 175085
chemistryofaziri00clourich_Page_028.jpg
G29 J29 135808
chemistryofaziri00clourich_Page_029.jpg
G30 J30 215746
chemistryofaziri00clourich_Page_030.jpg
G31 J31 273367
chemistryofaziri00clourich_Page_031.jpg
G32 J32 149891
chemistryofaziri00clourich_Page_032.jpg
G33 J33 229890
chemistryofaziri00clourich_Page_033.jpg
G34 J34 178262
chemistryofaziri00clourich_Page_034.jpg
G35 J35 145794
chemistryofaziri00clourich_Page_035.jpg
G36 J36 138829
chemistryofaziri00clourich_Page_036.jpg
G37 J37 192152
chemistryofaziri00clourich_Page_037.jpg
G38 J38 179039
chemistryofaziri00clourich_Page_038.jpg
G39 J39 189090
chemistryofaziri00clourich_Page_039.jpg
G40 J40 195498
chemistryofaziri00clourich_Page_040.jpg
G41 J41 177755
chemistryofaziri00clourich_Page_041.jpg
G42 J42 226810
chemistryofaziri00clourich_Page_042.jpg
G43 J43 170881
chemistryofaziri00clourich_Page_043.jpg
G44 J44 219205
chemistryofaziri00clourich_Page_044.jpg
G45 J45 235032
chemistryofaziri00clourich_Page_045.jpg
G46 J46 113349
chemistryofaziri00clourich_Page_046.jpg
G47 J47 209341
chemistryofaziri00clourich_Page_047.jpg
G48 J48 170263
chemistryofaziri00clourich_Page_048.jpg
G49 J49 114448
chemistryofaziri00clourich_Page_049.jpg
G50 J50 140364
chemistryofaziri00clourich_Page_050.jpg
G51 J51 179912
chemistryofaziri00clourich_Page_051.jpg
G52 J52 168986
chemistryofaziri00clourich_Page_052.jpg
G53 J53 161128
chemistryofaziri00clourich_Page_053.jpg
G54 J54 185011
chemistryofaziri00clourich_Page_054.jpg
G55 J55 134896
chemistryofaziri00clourich_Page_055.jpg
G56 J56 187950
chemistryofaziri00clourich_Page_056.jpg
G57 J57 184197
chemistryofaziri00clourich_Page_057.jpg
G58 J58 204966
chemistryofaziri00clourich_Page_058.jpg
G59 J59 133784
chemistryofaziri00clourich_Page_059.jpg
G60 J60 160276
chemistryofaziri00clourich_Page_060.jpg
G61 J61 219548
chemistryofaziri00clourich_Page_061.jpg
G62 J62 204357
chemistryofaziri00clourich_Page_062.jpg
G63 J63 107162
chemistryofaziri00clourich_Page_063.jpg
G64 J64 215170
chemistryofaziri00clourich_Page_064.jpg
G65 J65 202583
chemistryofaziri00clourich_Page_065.jpg
G66 J66 197135
chemistryofaziri00clourich_Page_066.jpg
G67 J67 176332
chemistryofaziri00clourich_Page_067.jpg
G68 J68 247522
chemistryofaziri00clourich_Page_068.jpg
G69 J69 240070
chemistryofaziri00clourich_Page_069.jpg
G70 J70 184462
chemistryofaziri00clourich_Page_070.jpg
G71 J71 206592
chemistryofaziri00clourich_Page_071.jpg
G72 J72 205629
chemistryofaziri00clourich_Page_072.jpg
G73 J73 216401
chemistryofaziri00clourich_Page_073.jpg
G74 J74 237739
chemistryofaziri00clourich_Page_074.jpg
G75 J75 259174
chemistryofaziri00clourich_Page_075.jpg
G76 J76 251324
chemistryofaziri00clourich_Page_076.jpg
G77 J77 258386
chemistryofaziri00clourich_Page_077.jpg
G78 J78 256190
chemistryofaziri00clourich_Page_078.jpg
G79 J79 258812
chemistryofaziri00clourich_Page_079.jpg
G80 J80 256720
chemistryofaziri00clourich_Page_080.jpg
G81 J81 249819
chemistryofaziri00clourich_Page_081.jpg
G82 J82 230286
chemistryofaziri00clourich_Page_082.jpg
G83 J83 249954
chemistryofaziri00clourich_Page_083.jpg
G84 J84 228811
chemistryofaziri00clourich_Page_084.jpg
G85 J85 258168
chemistryofaziri00clourich_Page_085.jpg
G86 J86 233986
chemistryofaziri00clourich_Page_086.jpg
G87 J87 241529
chemistryofaziri00clourich_Page_087.jpg
G88 J88 226721
chemistryofaziri00clourich_Page_088.jpg
G89 J89 245611
chemistryofaziri00clourich_Page_089.jpg
G90 J90 269019
chemistryofaziri00clourich_Page_090.jpg
G91 J91 263810
chemistryofaziri00clourich_Page_091.jpg
G92 J92 272112
chemistryofaziri00clourich_Page_092.jpg
G93 J93 242004
chemistryofaziri00clourich_Page_093.jpg
G94 J94 225307
chemistryofaziri00clourich_Page_094.jpg
G95 J95 247616
chemistryofaziri00clourich_Page_095.jpg
G96 J96 268565
chemistryofaziri00clourich_Page_096.jpg
G97 J97 264858
chemistryofaziri00clourich_Page_097.jpg
G98 J98 271942
chemistryofaziri00clourich_Page_098.jpg
G99 J99 265386
chemistryofaziri00clourich_Page_099.jpg
G100 J100 249664
chemistryofaziri00clourich_Page_100.jpg
G101 J101 266106
chemistryofaziri00clourich_Page_101.jpg
G102 J102 232143
chemistryofaziri00clourich_Page_102.jpg
G103 J103 247686
chemistryofaziri00clourich_Page_103.jpg
G104 J104 140027
chemistryofaziri00clourich_Page_104.jpg
G105 J105 55559
chemistryofaziri00clourich_Page_105.jpg
G106 J106 105543
chemistryofaziri00clourich_Page_106.jpg
G107 J107 128147
chemistryofaziri00clourich_Page_107.jpg
G108 J108 112757
chemistryofaziri00clourich_Page_108.jpg
G109 J109 137133
chemistryofaziri00clourich_Page_109.jpg
G110 J110 136740
chemistryofaziri00clourich_Page_110.jpg
G111 J111 154896
chemistryofaziri00clourich_Page_111.jpg
G112 J112 125502
chemistryofaziri00clourich_Page_112.jpg
G113 J113 137286
chemistryofaziri00clourich_Page_113.jpg
G114 J114 97572
chemistryofaziri00clourich_Page_114.jpg
G115 J115 127671
chemistryofaziri00clourich_Page_115.jpg
G116 J116 101596
chemistryofaziri00clourich_Page_116.jpg
G117 J117 128988
chemistryofaziri00clourich_Page_117.jpg
G118 J118 113870
chemistryofaziri00clourich_Page_118.jpg
G119 J119 134538
chemistryofaziri00clourich_Page_119.jpg
G120 J120 109979
chemistryofaziri00clourich_Page_120.jpg
G121 J121 133443
chemistryofaziri00clourich_Page_121.jpg
G122 J122 240852
chemistryofaziri00clourich_Page_122.jpg
G123 J123 325677
chemistryofaziri00clourich_Page_123.jpg
G124 J124 313688
chemistryofaziri00clourich_Page_124.jpg
G125 J125 321804
chemistryofaziri00clourich_Page_125.jpg
G126 J126 305908
chemistryofaziri00clourich_Page_126.jpg
G127 J127 154895
chemistryofaziri00clourich_Page_127.jpg
G128 J128 162864
chemistryofaziri00clourich_Page_128.jpg
G129 J129 155504
chemistryofaziri00clourich_Page_129.jpg
G130 J130 54890
chemistryofaziri00clourich_Page_130.jpg
E1 imagejp2 118637
chemistryofaziri00clourich_Page_001.jp2
E2 48527
chemistryofaziri00clourich_Page_002.jp2
E3 257162
chemistryofaziri00clourich_Page_003.jp2
E4 298903
chemistryofaziri00clourich_Page_004.jp2
E5 298937
chemistryofaziri00clourich_Page_005.jp2
E6 298906
chemistryofaziri00clourich_Page_006.jp2
E7 298905
chemistryofaziri00clourich_Page_007.jp2
E8 298930
chemistryofaziri00clourich_Page_008.jp2
E9 298938
chemistryofaziri00clourich_Page_009.jp2
E10 298931
chemistryofaziri00clourich_Page_010.jp2
E11 239264
chemistryofaziri00clourich_Page_011.jp2
E12 263003
chemistryofaziri00clourich_Page_012.jp2
E13 298642
chemistryofaziri00clourich_Page_013.jp2
E14 102488
chemistryofaziri00clourich_Page_014.jp2
E15
chemistryofaziri00clourich_Page_015.jp2
E16 305966
chemistryofaziri00clourich_Page_016.jp2
E17 298897
chemistryofaziri00clourich_Page_017.jp2
E18 319660
chemistryofaziri00clourich_Page_018.jp2
E19 271264
chemistryofaziri00clourich_Page_019.jp2
E20 307018
chemistryofaziri00clourich_Page_020.jp2
E21 291295
chemistryofaziri00clourich_Page_021.jp2
E22 319645
chemistryofaziri00clourich_Page_022.jp2
E23 298892
chemistryofaziri00clourich_Page_023.jp2
E24 319641
chemistryofaziri00clourich_Page_024.jp2
E25 298935
chemistryofaziri00clourich_Page_025.jp2
E26 319617
chemistryofaziri00clourich_Page_026.jp2
E27 298920
chemistryofaziri00clourich_Page_027.jp2
E28 319659
chemistryofaziri00clourich_Page_028.jp2
E29 254214
chemistryofaziri00clourich_Page_029.jp2
E30 319671
chemistryofaziri00clourich_Page_030.jp2
E31 308779
chemistryofaziri00clourich_Page_031.jp2
E32 281601
chemistryofaziri00clourich_Page_032.jp2
E33 317526
chemistryofaziri00clourich_Page_033.jp2
E34 319565
chemistryofaziri00clourich_Page_034.jp2
E35 270100
chemistryofaziri00clourich_Page_035.jp2
E36 255508
chemistryofaziri00clourich_Page_036.jp2
E37
chemistryofaziri00clourich_Page_037.jp2
E38 319625
chemistryofaziri00clourich_Page_038.jp2
E39 317503
chemistryofaziri00clourich_Page_039.jp2
E40 319657
chemistryofaziri00clourich_Page_040.jp2
E41 317484
chemistryofaziri00clourich_Page_041.jp2
E42 319669
chemistryofaziri00clourich_Page_042.jp2
E43 317508
chemistryofaziri00clourich_Page_043.jp2
E44
chemistryofaziri00clourich_Page_044.jp2
E45 317506
chemistryofaziri00clourich_Page_045.jp2
E46 200206
chemistryofaziri00clourich_Page_046.jp2
E47 317513
chemistryofaziri00clourich_Page_047.jp2
E48 319674
chemistryofaziri00clourich_Page_048.jp2
E49 193699
chemistryofaziri00clourich_Page_049.jp2
E50 256132
chemistryofaziri00clourich_Page_050.jp2
E51 317494
chemistryofaziri00clourich_Page_051.jp2
E52 319618
chemistryofaziri00clourich_Page_052.jp2
E53 305802
chemistryofaziri00clourich_Page_053.jp2
E54 319648
chemistryofaziri00clourich_Page_054.jp2
E55 250357
chemistryofaziri00clourich_Page_055.jp2
E56 319666
chemistryofaziri00clourich_Page_056.jp2
E57
chemistryofaziri00clourich_Page_057.jp2
E58 319652
chemistryofaziri00clourich_Page_058.jp2
E59 237464
chemistryofaziri00clourich_Page_059.jp2
E60 301506
chemistryofaziri00clourich_Page_060.jp2
E61 317500
chemistryofaziri00clourich_Page_061.jp2
E62
chemistryofaziri00clourich_Page_062.jp2
E63 172605
chemistryofaziri00clourich_Page_063.jp2
E64 319658
chemistryofaziri00clourich_Page_064.jp2
E65 317527
chemistryofaziri00clourich_Page_065.jp2
E66 319607
chemistryofaziri00clourich_Page_066.jp2
E67 317525
chemistryofaziri00clourich_Page_067.jp2
E68
chemistryofaziri00clourich_Page_068.jp2
E69 317490
chemistryofaziri00clourich_Page_069.jp2
E70 319639
chemistryofaziri00clourich_Page_070.jp2
E71
chemistryofaziri00clourich_Page_071.jp2
E72 319672
chemistryofaziri00clourich_Page_072.jp2
E73 317482
chemistryofaziri00clourich_Page_073.jp2
E74
chemistryofaziri00clourich_Page_074.jp2
E75
chemistryofaziri00clourich_Page_075.jp2
E76
chemistryofaziri00clourich_Page_076.jp2
E77 317511
chemistryofaziri00clourich_Page_077.jp2
E78 319662
chemistryofaziri00clourich_Page_078.jp2
E79 317416
chemistryofaziri00clourich_Page_079.jp2
E80 319632
chemistryofaziri00clourich_Page_080.jp2
E81 317524
chemistryofaziri00clourich_Page_081.jp2
E82 319543
chemistryofaziri00clourich_Page_082.jp2
E83
chemistryofaziri00clourich_Page_083.jp2
E84 319667
chemistryofaziri00clourich_Page_084.jp2
E85
chemistryofaziri00clourich_Page_085.jp2
E86 319558
chemistryofaziri00clourich_Page_086.jp2
E87 317464
chemistryofaziri00clourich_Page_087.jp2
E88
chemistryofaziri00clourich_Page_088.jp2
E89 317449
chemistryofaziri00clourich_Page_089.jp2
E90 319661
chemistryofaziri00clourich_Page_090.jp2
E91 317483
chemistryofaziri00clourich_Page_091.jp2
E92 319646
chemistryofaziri00clourich_Page_092.jp2
E93 317477
chemistryofaziri00clourich_Page_093.jp2
E94
chemistryofaziri00clourich_Page_094.jp2
E95 317472
chemistryofaziri00clourich_Page_095.jp2
E96 319643
chemistryofaziri00clourich_Page_096.jp2
E97
chemistryofaziri00clourich_Page_097.jp2
E98
chemistryofaziri00clourich_Page_098.jp2
E99
chemistryofaziri00clourich_Page_099.jp2
E100 319609
chemistryofaziri00clourich_Page_100.jp2
E101
chemistryofaziri00clourich_Page_101.jp2
E102
chemistryofaziri00clourich_Page_102.jp2
E103 317521
chemistryofaziri00clourich_Page_103.jp2
E104 251006
chemistryofaziri00clourich_Page_104.jp2
E105 51363
chemistryofaziri00clourich_Page_105.jp2
E106 172448
chemistryofaziri00clourich_Page_106.jp2
E107 218983
chemistryofaziri00clourich_Page_107.jp2
E108 186016
chemistryofaziri00clourich_Page_108.jp2
E109 238321
chemistryofaziri00clourich_Page_109.jp2
E110 236109
chemistryofaziri00clourich_Page_110.jp2
E111 277591
chemistryofaziri00clourich_Page_111.jp2
E112 206047
chemistryofaziri00clourich_Page_112.jp2
E113 242664
chemistryofaziri00clourich_Page_113.jp2
E114 157452
chemistryofaziri00clourich_Page_114.jp2
E115 215000
chemistryofaziri00clourich_Page_115.jp2
E116 164048
chemistryofaziri00clourich_Page_116.jp2
E117 213622
chemistryofaziri00clourich_Page_117.jp2
E118 190069
chemistryofaziri00clourich_Page_118.jp2
E119 230786
chemistryofaziri00clourich_Page_119.jp2
E120 180886
chemistryofaziri00clourich_Page_120.jp2
E121 228942
chemistryofaziri00clourich_Page_121.jp2
E122 319616
chemistryofaziri00clourich_Page_122.jp2
E123 317519
chemistryofaziri00clourich_Page_123.jp2
E124
chemistryofaziri00clourich_Page_124.jp2
E125 317480
chemistryofaziri00clourich_Page_125.jp2
E126 319619
chemistryofaziri00clourich_Page_126.jp2
E127 280392
chemistryofaziri00clourich_Page_127.jp2
E128 296000
chemistryofaziri00clourich_Page_128.jp2
E129 307539
chemistryofaziri00clourich_Page_129.jp2
E130 46606
chemistryofaziri00clourich_Page_130.jp2
archive
F1 imagetiff 6.0 7179584
chemistryofaziri00clourich_Page_001.tif
F2
chemistryofaziri00clourich_Page_002.tif
F3
chemistryofaziri00clourich_Page_003.tif
F4
chemistryofaziri00clourich_Page_004.tif
F5
chemistryofaziri00clourich_Page_005.tif
F6
chemistryofaziri00clourich_Page_006.tif
F7
chemistryofaziri00clourich_Page_007.tif
F8
chemistryofaziri00clourich_Page_008.tif
F9
chemistryofaziri00clourich_Page_009.tif
F10
chemistryofaziri00clourich_Page_010.tif
F11
chemistryofaziri00clourich_Page_011.tif
F12
chemistryofaziri00clourich_Page_012.tif
F13
chemistryofaziri00clourich_Page_013.tif
F14
chemistryofaziri00clourich_Page_014.tif
F15
chemistryofaziri00clourich_Page_015.tif
F16 7348334
chemistryofaziri00clourich_Page_016.tif
F17
chemistryofaziri00clourich_Page_017.tif
F18 7677358
chemistryofaziri00clourich_Page_018.tif
F19
chemistryofaziri00clourich_Page_019.tif
F20
chemistryofaziri00clourich_Page_020.tif
F21
chemistryofaziri00clourich_Page_021.tif
F22
chemistryofaziri00clourich_Page_022.tif
F23
chemistryofaziri00clourich_Page_023.tif
F24
chemistryofaziri00clourich_Page_024.tif
F25
chemistryofaziri00clourich_Page_025.tif
F26
chemistryofaziri00clourich_Page_026.tif
F27
chemistryofaziri00clourich_Page_027.tif
F28
chemistryofaziri00clourich_Page_028.tif
F29 7415834
chemistryofaziri00clourich_Page_029.tif
F30
chemistryofaziri00clourich_Page_030.tif
F31
chemistryofaziri00clourich_Page_031.tif
F32
chemistryofaziri00clourich_Page_032.tif
F33 7625966
chemistryofaziri00clourich_Page_033.tif
F34
chemistryofaziri00clourich_Page_034.tif
F35
chemistryofaziri00clourich_Page_035.tif
F36
chemistryofaziri00clourich_Page_036.tif
F37
chemistryofaziri00clourich_Page_037.tif
F38
chemistryofaziri00clourich_Page_038.tif
F39
chemistryofaziri00clourich_Page_039.tif
F40
chemistryofaziri00clourich_Page_040.tif
F41
chemistryofaziri00clourich_Page_041.tif
F42
chemistryofaziri00clourich_Page_042.tif
F43
chemistryofaziri00clourich_Page_043.tif
F44
chemistryofaziri00clourich_Page_044.tif
F45
chemistryofaziri00clourich_Page_045.tif
F46
chemistryofaziri00clourich_Page_046.tif
F47
chemistryofaziri00clourich_Page_047.tif
F48
chemistryofaziri00clourich_Page_048.tif
F49
chemistryofaziri00clourich_Page_049.tif
F50
chemistryofaziri00clourich_Page_050.tif
F51
chemistryofaziri00clourich_Page_051.tif
F52
chemistryofaziri00clourich_Page_052.tif
F53
chemistryofaziri00clourich_Page_053.tif
F54
chemistryofaziri00clourich_Page_054.tif
F55
chemistryofaziri00clourich_Page_055.tif
F56
chemistryofaziri00clourich_Page_056.tif
F57
chemistryofaziri00clourich_Page_057.tif
F58
chemistryofaziri00clourich_Page_058.tif
F59
chemistryofaziri00clourich_Page_059.tif
F60
chemistryofaziri00clourich_Page_060.tif
F61
chemistryofaziri00clourich_Page_061.tif
F62
chemistryofaziri00clourich_Page_062.tif
F63
chemistryofaziri00clourich_Page_063.tif
F64
chemistryofaziri00clourich_Page_064.tif
F65
chemistryofaziri00clourich_Page_065.tif
F66
chemistryofaziri00clourich_Page_066.tif
F67
chemistryofaziri00clourich_Page_067.tif
F68
chemistryofaziri00clourich_Page_068.tif
F69
chemistryofaziri00clourich_Page_069.tif
F70
chemistryofaziri00clourich_Page_070.tif
F71
chemistryofaziri00clourich_Page_071.tif
F72
chemistryofaziri00clourich_Page_072.tif
F73
chemistryofaziri00clourich_Page_073.tif
F74
chemistryofaziri00clourich_Page_074.tif
F75
chemistryofaziri00clourich_Page_075.tif
F76
chemistryofaziri00clourich_Page_076.tif
F77
chemistryofaziri00clourich_Page_077.tif
F78
chemistryofaziri00clourich_Page_078.tif
F79
chemistryofaziri00clourich_Page_079.tif
F80
chemistryofaziri00clourich_Page_080.tif
F81
chemistryofaziri00clourich_Page_081.tif
F82
chemistryofaziri00clourich_Page_082.tif
F83
chemistryofaziri00clourich_Page_083.tif
F84
chemistryofaziri00clourich_Page_084.tif
F85
chemistryofaziri00clourich_Page_085.tif
F86
chemistryofaziri00clourich_Page_086.tif
F87
chemistryofaziri00clourich_Page_087.tif
F88
chemistryofaziri00clourich_Page_088.tif
F89
chemistryofaziri00clourich_Page_089.tif
F90
chemistryofaziri00clourich_Page_090.tif
F91
chemistryofaziri00clourich_Page_091.tif
F92
chemistryofaziri00clourich_Page_092.tif
F93
chemistryofaziri00clourich_Page_093.tif
F94
chemistryofaziri00clourich_Page_094.tif
F95
chemistryofaziri00clourich_Page_095.tif
F96
chemistryofaziri00clourich_Page_096.tif
F97
chemistryofaziri00clourich_Page_097.tif
F98
chemistryofaziri00clourich_Page_098.tif
F99
chemistryofaziri00clourich_Page_099.tif
F100
chemistryofaziri00clourich_Page_100.tif
F101
chemistryofaziri00clourich_Page_101.tif
F102
chemistryofaziri00clourich_Page_102.tif
F103
chemistryofaziri00clourich_Page_103.tif
F104
chemistryofaziri00clourich_Page_104.tif
F105
chemistryofaziri00clourich_Page_105.tif
F106
chemistryofaziri00clourich_Page_106.tif
F107
chemistryofaziri00clourich_Page_107.tif
F108
chemistryofaziri00clourich_Page_108.tif
F109
chemistryofaziri00clourich_Page_109.tif
F110
chemistryofaziri00clourich_Page_110.tif
F111
chemistryofaziri00clourich_Page_111.tif
F112
chemistryofaziri00clourich_Page_112.tif
F113
chemistryofaziri00clourich_Page_113.tif
F114
chemistryofaziri00clourich_Page_114.tif
F115
chemistryofaziri00clourich_Page_115.tif
F116
chemistryofaziri00clourich_Page_116.tif
F117
chemistryofaziri00clourich_Page_117.tif
F118
chemistryofaziri00clourich_Page_118.tif
F119
chemistryofaziri00clourich_Page_119.tif
F120
chemistryofaziri00clourich_Page_120.tif
F121
chemistryofaziri00clourich_Page_121.tif
F122
chemistryofaziri00clourich_Page_122.tif
F123
chemistryofaziri00clourich_Page_123.tif
F124
chemistryofaziri00clourich_Page_124.tif
F125
chemistryofaziri00clourich_Page_125.tif
F126
chemistryofaziri00clourich_Page_126.tif
F127
chemistryofaziri00clourich_Page_127.tif
F128
chemistryofaziri00clourich_Page_128.tif
F129
chemistryofaziri00clourich_Page_129.tif
F130
chemistryofaziri00clourich_Page_130.tif
R1 textx-pro 6726
chemistryofaziri00clourich_Page_001.pro
R2 526
chemistryofaziri00clourich_Page_002.pro
R3 18931
chemistryofaziri00clourich_Page_003.pro
R4 37668
chemistryofaziri00clourich_Page_004.pro
R5 38496
chemistryofaziri00clourich_Page_005.pro
R6 37401
chemistryofaziri00clourich_Page_006.pro
R7 34730
chemistryofaziri00clourich_Page_007.pro
R8 33875
chemistryofaziri00clourich_Page_008.pro
R9 26895
chemistryofaziri00clourich_Page_009.pro
R10 22186
chemistryofaziri00clourich_Page_010.pro
R11 13257
chemistryofaziri00clourich_Page_011.pro
R12 20363
chemistryofaziri00clourich_Page_012.pro
R13 31794
chemistryofaziri00clourich_Page_013.pro
R14 4268
chemistryofaziri00clourich_Page_014.pro
R15 38176
chemistryofaziri00clourich_Page_015.pro
R16 39465
chemistryofaziri00clourich_Page_016.pro
R17 39586
chemistryofaziri00clourich_Page_017.pro
R18 36578
chemistryofaziri00clourich_Page_018.pro
R19 21519
chemistryofaziri00clourich_Page_019.pro
R20 20439
chemistryofaziri00clourich_Page_020.pro
R21 18159
chemistryofaziri00clourich_Page_021.pro
R22 35017
chemistryofaziri00clourich_Page_022.pro
R23 21949
chemistryofaziri00clourich_Page_023.pro
R24 20664
chemistryofaziri00clourich_Page_024.pro
R25 17323
chemistryofaziri00clourich_Page_025.pro
R26 30619
chemistryofaziri00clourich_Page_026.pro
R27 35576
chemistryofaziri00clourich_Page_027.pro
R28 20994
chemistryofaziri00clourich_Page_028.pro
R29 13206
chemistryofaziri00clourich_Page_029.pro
R30 33232
chemistryofaziri00clourich_Page_030.pro
R31 43184
chemistryofaziri00clourich_Page_031.pro
R32 17917
chemistryofaziri00clourich_Page_032.pro
R33 35953
chemistryofaziri00clourich_Page_033.pro
R34 24387
chemistryofaziri00clourich_Page_034.pro
R35 16388
chemistryofaziri00clourich_Page_035.pro
R36 17454
chemistryofaziri00clourich_Page_036.pro
R37 27912
chemistryofaziri00clourich_Page_037.pro
R38 23019
chemistryofaziri00clourich_Page_038.pro
R39 23940
chemistryofaziri00clourich_Page_039.pro
R40 27592
chemistryofaziri00clourich_Page_040.pro
R41 23259
chemistryofaziri00clourich_Page_041.pro
R42 34884
chemistryofaziri00clourich_Page_042.pro
R43 19452
chemistryofaziri00clourich_Page_043.pro
R44 33144
chemistryofaziri00clourich_Page_044.pro
R45 35565
chemistryofaziri00clourich_Page_045.pro
R46 10356
chemistryofaziri00clourich_Page_046.pro
R47 30805
chemistryofaziri00clourich_Page_047.pro
R48 21794
chemistryofaziri00clourich_Page_048.pro
R49 9355
chemistryofaziri00clourich_Page_049.pro
R50 13246
chemistryofaziri00clourich_Page_050.pro
R51 22830
chemistryofaziri00clourich_Page_051.pro
R52 24336
chemistryofaziri00clourich_Page_052.pro
R53 22402
chemistryofaziri00clourich_Page_053.pro
R54 27846
chemistryofaziri00clourich_Page_054.pro
R55 14076
chemistryofaziri00clourich_Page_055.pro
R56 26522
chemistryofaziri00clourich_Page_056.pro
R57 25937
chemistryofaziri00clourich_Page_057.pro
R58 31004
chemistryofaziri00clourich_Page_058.pro
R59 16379
chemistryofaziri00clourich_Page_059.pro
R60 26855
chemistryofaziri00clourich_Page_060.pro
R61 34017
chemistryofaziri00clourich_Page_061.pro
R62 29046
chemistryofaziri00clourich_Page_062.pro
R63 9326
chemistryofaziri00clourich_Page_063.pro
R64 29563
chemistryofaziri00clourich_Page_064.pro
R65 26379
chemistryofaziri00clourich_Page_065.pro
R66 28440
chemistryofaziri00clourich_Page_066.pro
R67 20628
chemistryofaziri00clourich_Page_067.pro
R68 38793
chemistryofaziri00clourich_Page_068.pro
R69 35248
chemistryofaziri00clourich_Page_069.pro
R70 27387
chemistryofaziri00clourich_Page_070.pro
R71 28377
chemistryofaziri00clourich_Page_071.pro
R72 31840
chemistryofaziri00clourich_Page_072.pro
R73 30351
chemistryofaziri00clourich_Page_073.pro
R74 38208
chemistryofaziri00clourich_Page_074.pro
R75 38110
chemistryofaziri00clourich_Page_075.pro
R76 38573
chemistryofaziri00clourich_Page_076.pro
R77 40885
chemistryofaziri00clourich_Page_077.pro
R78 41652
chemistryofaziri00clourich_Page_078.pro
R79 39806
chemistryofaziri00clourich_Page_079.pro
R80 38644
chemistryofaziri00clourich_Page_080.pro
R81 37738
chemistryofaziri00clourich_Page_081.pro
R82 33905
chemistryofaziri00clourich_Page_082.pro
R83 39436
chemistryofaziri00clourich_Page_083.pro
R84 33127
chemistryofaziri00clourich_Page_084.pro
R85 42800
chemistryofaziri00clourich_Page_085.pro
R86 35998
chemistryofaziri00clourich_Page_086.pro
R87 36058
chemistryofaziri00clourich_Page_087.pro
R88 35768
chemistryofaziri00clourich_Page_088.pro
R89 42059
chemistryofaziri00clourich_Page_089.pro
R90 41086
chemistryofaziri00clourich_Page_090.pro
R91 41902
chemistryofaziri00clourich_Page_091.pro
R92 41509
chemistryofaziri00clourich_Page_092.pro
R93 38217
chemistryofaziri00clourich_Page_093.pro
R94 33284
chemistryofaziri00clourich_Page_094.pro
R95 36179
chemistryofaziri00clourich_Page_095.pro
R96 44556
chemistryofaziri00clourich_Page_096.pro
R97 40714
chemistryofaziri00clourich_Page_097.pro
R98 43772
chemistryofaziri00clourich_Page_098.pro
R99 42079
chemistryofaziri00clourich_Page_099.pro
R100 40636
chemistryofaziri00clourich_Page_100.pro
R101 43485
chemistryofaziri00clourich_Page_101.pro
R102 36405
chemistryofaziri00clourich_Page_102.pro
R103 39620
chemistryofaziri00clourich_Page_103.pro
R104 16631
chemistryofaziri00clourich_Page_104.pro
R105 501
chemistryofaziri00clourich_Page_105.pro
R106 9262
chemistryofaziri00clourich_Page_106.pro
R107 4136
chemistryofaziri00clourich_Page_107.pro
R108 11026
chemistryofaziri00clourich_Page_108.pro
R109 2053
chemistryofaziri00clourich_Page_109.pro
R110 13645
chemistryofaziri00clourich_Page_110.pro
R111 2087
chemistryofaziri00clourich_Page_111.pro
R112 12121
chemistryofaziri00clourich_Page_112.pro
R113 1146
chemistryofaziri00clourich_Page_113.pro
R114 7987
chemistryofaziri00clourich_Page_114.pro
R115 2621
chemistryofaziri00clourich_Page_115.pro
R116 9133
chemistryofaziri00clourich_Page_116.pro
R117 2164
chemistryofaziri00clourich_Page_117.pro
R118 10606
chemistryofaziri00clourich_Page_118.pro
R119 2593
chemistryofaziri00clourich_Page_119.pro
R120 9217
chemistryofaziri00clourich_Page_120.pro
R121 2922
chemistryofaziri00clourich_Page_121.pro
R122 41289
chemistryofaziri00clourich_Page_122.pro
R123 59954
chemistryofaziri00clourich_Page_123.pro
R124 50447
chemistryofaziri00clourich_Page_124.pro
R125 54994
chemistryofaziri00clourich_Page_125.pro
R126 54478
chemistryofaziri00clourich_Page_126.pro
R127 20752
chemistryofaziri00clourich_Page_127.pro
R128 19776
chemistryofaziri00clourich_Page_128.pro
R129 13428
chemistryofaziri00clourich_Page_129.pro
T1 textplain 404
chemistryofaziri00clourich_Page_001.txt
T2 76
chemistryofaziri00clourich_Page_002.txt
T3 806
chemistryofaziri00clourich_Page_003.txt
T4 1619
chemistryofaziri00clourich_Page_004.txt
T5 1866
chemistryofaziri00clourich_Page_005.txt
T6 1781
chemistryofaziri00clourich_Page_006.txt
T7 1604
chemistryofaziri00clourich_Page_007.txt
T8 1598
chemistryofaziri00clourich_Page_008.txt
T9 1345
chemistryofaziri00clourich_Page_009.txt
T10 1107
chemistryofaziri00clourich_Page_010.txt
T11 718
chemistryofaziri00clourich_Page_011.txt
T12 974
chemistryofaziri00clourich_Page_012.txt
T13 1531
chemistryofaziri00clourich_Page_013.txt
T14 193
chemistryofaziri00clourich_Page_014.txt
T15 1621
chemistryofaziri00clourich_Page_015.txt
T16 1962
chemistryofaziri00clourich_Page_016.txt
T17 1826
chemistryofaziri00clourich_Page_017.txt
T18 1632
chemistryofaziri00clourich_Page_018.txt
T19 1025
chemistryofaziri00clourich_Page_019.txt
T20 930
chemistryofaziri00clourich_Page_020.txt
T21 835
chemistryofaziri00clourich_Page_021.txt
T22 1625
chemistryofaziri00clourich_Page_022.txt
T23 1106
chemistryofaziri00clourich_Page_023.txt
T24 963
chemistryofaziri00clourich_Page_024.txt
T25 866
chemistryofaziri00clourich_Page_025.txt
T26 1464
chemistryofaziri00clourich_Page_026.txt
T27
chemistryofaziri00clourich_Page_027.txt
T28 1024
chemistryofaziri00clourich_Page_028.txt
T29 708
chemistryofaziri00clourich_Page_029.txt
T30 1683
chemistryofaziri00clourich_Page_030.txt
T31 1896
chemistryofaziri00clourich_Page_031.txt
T32 1143
chemistryofaziri00clourich_Page_032.txt
T33 1620
chemistryofaziri00clourich_Page_033.txt
T34 1138
chemistryofaziri00clourich_Page_034.txt
T35 884
chemistryofaziri00clourich_Page_035.txt
T36 1048
chemistryofaziri00clourich_Page_036.txt
T37 1363
chemistryofaziri00clourich_Page_037.txt
T38 1114
chemistryofaziri00clourich_Page_038.txt
T39 1254
chemistryofaziri00clourich_Page_039.txt
T40 1463
chemistryofaziri00clourich_Page_040.txt
T41 1086
chemistryofaziri00clourich_Page_041.txt
T42 1654
chemistryofaziri00clourich_Page_042.txt
T43 931
chemistryofaziri00clourich_Page_043.txt
T44 1700
chemistryofaziri00clourich_Page_044.txt
T45 1722
chemistryofaziri00clourich_Page_045.txt
T46 505
chemistryofaziri00clourich_Page_046.txt
T47 1627
chemistryofaziri00clourich_Page_047.txt
T48 1192
chemistryofaziri00clourich_Page_048.txt
T49 480
chemistryofaziri00clourich_Page_049.txt
T50 721
chemistryofaziri00clourich_Page_050.txt
T51 1145
chemistryofaziri00clourich_Page_051.txt
T52 1343
chemistryofaziri00clourich_Page_052.txt
T53 1264
chemistryofaziri00clourich_Page_053.txt
T54 1411
chemistryofaziri00clourich_Page_054.txt
T55 625
chemistryofaziri00clourich_Page_055.txt
T56 1514
chemistryofaziri00clourich_Page_056.txt
T57 1372
chemistryofaziri00clourich_Page_057.txt
T58 1291
chemistryofaziri00clourich_Page_058.txt
T59 881
chemistryofaziri00clourich_Page_059.txt
T60
chemistryofaziri00clourich_Page_060.txt
T61 1588
chemistryofaziri00clourich_Page_061.txt
T62 1395
chemistryofaziri00clourich_Page_062.txt
T63 496
chemistryofaziri00clourich_Page_063.txt
T64 1403
chemistryofaziri00clourich_Page_064.txt
T65 1478
chemistryofaziri00clourich_Page_065.txt
T66 1290
chemistryofaziri00clourich_Page_066.txt
T67 1190
chemistryofaziri00clourich_Page_067.txt
T68 1711
chemistryofaziri00clourich_Page_068.txt
T69 1631
chemistryofaziri00clourich_Page_069.txt
T70 1452
chemistryofaziri00clourich_Page_070.txt
T71 1423
chemistryofaziri00clourich_Page_071.txt
T72 1393
chemistryofaziri00clourich_Page_072.txt
T73
chemistryofaziri00clourich_Page_073.txt
T74
chemistryofaziri00clourich_Page_074.txt
T75 1734
chemistryofaziri00clourich_Page_075.txt
T76 1690
chemistryofaziri00clourich_Page_076.txt
T77 1720
chemistryofaziri00clourich_Page_077.txt
T78
chemistryofaziri00clourich_Page_078.txt
T79 1909
chemistryofaziri00clourich_Page_079.txt
T80 1728
chemistryofaziri00clourich_Page_080.txt
T81 1697
chemistryofaziri00clourich_Page_081.txt
T82 1503
chemistryofaziri00clourich_Page_082.txt
T83 1695
chemistryofaziri00clourich_Page_083.txt
T84 1495
chemistryofaziri00clourich_Page_084.txt
T85 1812
chemistryofaziri00clourich_Page_085.txt
T86 1609
chemistryofaziri00clourich_Page_086.txt
T87 1559
chemistryofaziri00clourich_Page_087.txt
T88 1504
chemistryofaziri00clourich_Page_088.txt
T89 1779
chemistryofaziri00clourich_Page_089.txt
T90 1807
chemistryofaziri00clourich_Page_090.txt
T91 1889
chemistryofaziri00clourich_Page_091.txt
T92
chemistryofaziri00clourich_Page_092.txt
T93 1721
chemistryofaziri00clourich_Page_093.txt
T94 1408
chemistryofaziri00clourich_Page_094.txt
T95 1640
chemistryofaziri00clourich_Page_095.txt
T96 1859
chemistryofaziri00clourich_Page_096.txt
T97 1799
chemistryofaziri00clourich_Page_097.txt
T98 1841
chemistryofaziri00clourich_Page_098.txt
T99 1832
chemistryofaziri00clourich_Page_099.txt
T100 1669
chemistryofaziri00clourich_Page_100.txt
T101 1802
chemistryofaziri00clourich_Page_101.txt
T102
chemistryofaziri00clourich_Page_102.txt
T103 1687
chemistryofaziri00clourich_Page_103.txt
T104 793
chemistryofaziri00clourich_Page_104.txt
T105 87
chemistryofaziri00clourich_Page_105.txt
T106 583
chemistryofaziri00clourich_Page_106.txt
T107 146
chemistryofaziri00clourich_Page_107.txt
T108 610
chemistryofaziri00clourich_Page_108.txt
T109 134
chemistryofaziri00clourich_Page_109.txt
T110 693
chemistryofaziri00clourich_Page_110.txt
T111 263
chemistryofaziri00clourich_Page_111.txt
T112 671
chemistryofaziri00clourich_Page_112.txt
T113 129
chemistryofaziri00clourich_Page_113.txt
T114 417
chemistryofaziri00clourich_Page_114.txt
T115 372
chemistryofaziri00clourich_Page_115.txt
T116 486
chemistryofaziri00clourich_Page_116.txt
T117 161
chemistryofaziri00clourich_Page_117.txt
T118 612
chemistryofaziri00clourich_Page_118.txt
T119 478
chemistryofaziri00clourich_Page_119.txt
T120 536
chemistryofaziri00clourich_Page_120.txt
T121 132
chemistryofaziri00clourich_Page_121.txt
T122 1854
chemistryofaziri00clourich_Page_122.txt
T123 2649
chemistryofaziri00clourich_Page_123.txt
T124 2226
chemistryofaziri00clourich_Page_124.txt
T125 2383
chemistryofaziri00clourich_Page_125.txt
T126 2341
chemistryofaziri00clourich_Page_126.txt
T127 997
chemistryofaziri00clourich_Page_127.txt
T128 847
chemistryofaziri00clourich_Page_128.txt
T129 710
chemistryofaziri00clourich_Page_129.txt
UR1 18941
chemistryofaziri00clourich_Page_001thm.jpg
applicationpdf 4373316
chemistryofaziri00clourich.pdf
AR1 39471
chemistryofaziri00clourich_Page_001.QC.jpg
AR2 27951
chemistryofaziri00clourich_Page_002.QC.jpg
AR3 15491
chemistryofaziri00clourich_Page_002thm.jpg
AR4 60942
chemistryofaziri00clourich_Page_003.QC.jpg
AR5 25325
chemistryofaziri00clourich_Page_003thm.jpg
AR6 87367
chemistryofaziri00clourich_Page_004.QC.jpg
AR7 32747
chemistryofaziri00clourich_Page_004thm.jpg
AR8 100905
chemistryofaziri00clourich_Page_005.QC.jpg
AR9 35656
chemistryofaziri00clourich_Page_005thm.jpg
AR10 92902
chemistryofaziri00clourich_Page_006.QC.jpg
AR11 33290
chemistryofaziri00clourich_Page_006thm.jpg
AR12 88701
chemistryofaziri00clourich_Page_007.QC.jpg
AR13 32654
chemistryofaziri00clourich_Page_007thm.jpg
AR14 85811
chemistryofaziri00clourich_Page_008.QC.jpg
AR15 31710
chemistryofaziri00clourich_Page_008thm.jpg
AR16 73827
chemistryofaziri00clourich_Page_009.QC.jpg
AR17 29960
chemistryofaziri00clourich_Page_009thm.jpg
AR18 73059
chemistryofaziri00clourich_Page_010.QC.jpg
AR19 30158
chemistryofaziri00clourich_Page_010thm.jpg
AR20 59204
chemistryofaziri00clourich_Page_011.QC.jpg
AR21 26669
chemistryofaziri00clourich_Page_011thm.jpg
AR22 62637
chemistryofaziri00clourich_Page_012.QC.jpg
AR23 26261
chemistryofaziri00clourich_Page_012thm.jpg
AR24 88320
chemistryofaziri00clourich_Page_013.QC.jpg
AR25 33313
chemistryofaziri00clourich_Page_013thm.jpg
AR26 37826
chemistryofaziri00clourich_Page_014.QC.jpg
AR27 18197
chemistryofaziri00clourich_Page_014thm.jpg
AR28 105968
chemistryofaziri00clourich_Page_015.QC.jpg
AR29 37479
chemistryofaziri00clourich_Page_015thm.jpg
AR30 105800
chemistryofaziri00clourich_Page_016.QC.jpg
AR31 37854
chemistryofaziri00clourich_Page_016thm.jpg
AR32 99094
chemistryofaziri00clourich_Page_017.QC.jpg
AR33 38822
chemistryofaziri00clourich_Page_017thm.jpg
AR34 98961
chemistryofaziri00clourich_Page_018.QC.jpg
AR35 34832
chemistryofaziri00clourich_Page_018thm.jpg
AR36 63041
chemistryofaziri00clourich_Page_019.QC.jpg
AR37 27676
chemistryofaziri00clourich_Page_019thm.jpg
AR38 67808
chemistryofaziri00clourich_Page_020.QC.jpg
AR39 28244
chemistryofaziri00clourich_Page_020thm.jpg
AR40 70039
chemistryofaziri00clourich_Page_021.QC.jpg
AR41 28136
chemistryofaziri00clourich_Page_021thm.jpg
AR42 95996
chemistryofaziri00clourich_Page_022.QC.jpg
AR43 34833
chemistryofaziri00clourich_Page_022thm.jpg
AR44 74516
chemistryofaziri00clourich_Page_023.QC.jpg
AR45 29446
chemistryofaziri00clourich_Page_023thm.jpg
AR46 73914
chemistryofaziri00clourich_Page_024.QC.jpg
AR47
chemistryofaziri00clourich_Page_024thm.jpg
AR48 64304
chemistryofaziri00clourich_Page_025.QC.jpg
AR49 27559
chemistryofaziri00clourich_Page_025thm.jpg
AR50 86892
chemistryofaziri00clourich_Page_026.QC.jpg
AR51 32854
chemistryofaziri00clourich_Page_026thm.jpg
AR52 90484
chemistryofaziri00clourich_Page_027.QC.jpg
AR53 35131
chemistryofaziri00clourich_Page_027thm.jpg
AR54 74593
chemistryofaziri00clourich_Page_028.QC.jpg
AR55 29818
chemistryofaziri00clourich_Page_028thm.jpg
AR56 57368
chemistryofaziri00clourich_Page_029.QC.jpg
AR57 25062
chemistryofaziri00clourich_Page_029thm.jpg
AR58 90890
chemistryofaziri00clourich_Page_030.QC.jpg
AR59 33051
chemistryofaziri00clourich_Page_030thm.jpg
AR60 110106
chemistryofaziri00clourich_Page_031.QC.jpg
AR61 39378
chemistryofaziri00clourich_Page_031thm.jpg
AR62 64108
chemistryofaziri00clourich_Page_032.QC.jpg
AR63 26101
chemistryofaziri00clourich_Page_032thm.jpg
AR64 92971
chemistryofaziri00clourich_Page_033.QC.jpg
AR65 35294
chemistryofaziri00clourich_Page_033thm.jpg
AR66 71580
chemistryofaziri00clourich_Page_034.QC.jpg
AR67 28648
chemistryofaziri00clourich_Page_034thm.jpg
AR68 62111
chemistryofaziri00clourich_Page_035.QC.jpg
AR69 26692
chemistryofaziri00clourich_Page_035thm.jpg
AR70 59181
chemistryofaziri00clourich_Page_036.QC.jpg
AR71 25241
chemistryofaziri00clourich_Page_036thm.jpg
AR72 78835
chemistryofaziri00clourich_Page_037.QC.jpg
AR73 31120
chemistryofaziri00clourich_Page_037thm.jpg
AR74 75859
chemistryofaziri00clourich_Page_038.QC.jpg
AR75 30140
chemistryofaziri00clourich_Page_038thm.jpg
AR76 79718
chemistryofaziri00clourich_Page_039.QC.jpg
AR77 31967
chemistryofaziri00clourich_Page_039thm.jpg
AR78 77998
chemistryofaziri00clourich_Page_040.QC.jpg
AR79 29696
chemistryofaziri00clourich_Page_040thm.jpg
AR80 75498
chemistryofaziri00clourich_Page_041.QC.jpg
AR81 30057
chemistryofaziri00clourich_Page_041thm.jpg
AR82 92678
chemistryofaziri00clourich_Page_042.QC.jpg
AR83 34404
chemistryofaziri00clourich_Page_042thm.jpg
AR84 70869
chemistryofaziri00clourich_Page_043.QC.jpg
AR85 29580
chemistryofaziri00clourich_Page_043thm.jpg
AR86 90948
chemistryofaziri00clourich_Page_044.QC.jpg
AR87 33050
chemistryofaziri00clourich_Page_044thm.jpg
AR88 95915
chemistryofaziri00clourich_Page_045.QC.jpg
AR89 34938
chemistryofaziri00clourich_Page_045thm.jpg
AR90 49088
chemistryofaziri00clourich_Page_046.QC.jpg
AR91 22323
chemistryofaziri00clourich_Page_046thm.jpg
AR92 87981
chemistryofaziri00clourich_Page_047.QC.jpg
AR93 32332
chemistryofaziri00clourich_Page_047thm.jpg
AR94 71982
chemistryofaziri00clourich_Page_048.QC.jpg
AR95 28815
chemistryofaziri00clourich_Page_048thm.jpg
AR96 47557
chemistryofaziri00clourich_Page_049.QC.jpg
AR97 22297
chemistryofaziri00clourich_Page_049thm.jpg
AR98 59243
chemistryofaziri00clourich_Page_050.QC.jpg
AR99 26267
chemistryofaziri00clourich_Page_050thm.jpg
AR100 77029
chemistryofaziri00clourich_Page_051.QC.jpg
AR101 29235
chemistryofaziri00clourich_Page_051thm.jpg
AR102 70004
chemistryofaziri00clourich_Page_052.QC.jpg
AR103 27615
chemistryofaziri00clourich_Page_052thm.jpg
AR104 66635
chemistryofaziri00clourich_Page_053.QC.jpg
AR105 26689
chemistryofaziri00clourich_Page_053thm.jpg
AR106 78324
chemistryofaziri00clourich_Page_054.QC.jpg
AR107 30045
chemistryofaziri00clourich_Page_054thm.jpg
AR108 58311
chemistryofaziri00clourich_Page_055.QC.jpg
AR109 24843
chemistryofaziri00clourich_Page_055thm.jpg
AR110 78380
chemistryofaziri00clourich_Page_056.QC.jpg
AR111 30622
chemistryofaziri00clourich_Page_056thm.jpg
AR112 78453
chemistryofaziri00clourich_Page_057.QC.jpg
AR113 30152
chemistryofaziri00clourich_Page_057thm.jpg
AR114 83408
chemistryofaziri00clourich_Page_058.QC.jpg
AR115 31418
chemistryofaziri00clourich_Page_058thm.jpg
AR116 58645
chemistryofaziri00clourich_Page_059.QC.jpg
AR117 25120
chemistryofaziri00clourich_Page_059thm.jpg
AR118 68449
chemistryofaziri00clourich_Page_060.QC.jpg
AR119 28264
chemistryofaziri00clourich_Page_060thm.jpg
AR120 90633
chemistryofaziri00clourich_Page_061.QC.jpg
AR121 33649
chemistryofaziri00clourich_Page_061thm.jpg
AR122 85834
chemistryofaziri00clourich_Page_062.QC.jpg
AR123 32052
chemistryofaziri00clourich_Page_062thm.jpg
AR124 48191
chemistryofaziri00clourich_Page_063.QC.jpg
AR125 22164
chemistryofaziri00clourich_Page_063thm.jpg
AR126 81947
chemistryofaziri00clourich_Page_064.QC.jpg
AR127 32349
chemistryofaziri00clourich_Page_064thm.jpg
AR128 83187
chemistryofaziri00clourich_Page_065.QC.jpg
AR129 31413
chemistryofaziri00clourich_Page_065thm.jpg
AR130 81290
chemistryofaziri00clourich_Page_066.QC.jpg
AR131 32229
chemistryofaziri00clourich_Page_066thm.jpg
AR132 74951
chemistryofaziri00clourich_Page_067.QC.jpg
AR133 30063
chemistryofaziri00clourich_Page_067thm.jpg
AR134 100950
chemistryofaziri00clourich_Page_068.QC.jpg
AR135 36722
chemistryofaziri00clourich_Page_068thm.jpg
AR136 99509
chemistryofaziri00clourich_Page_069.QC.jpg
AR137 35961
chemistryofaziri00clourich_Page_069thm.jpg
AR138 73477
chemistryofaziri00clourich_Page_070.QC.jpg
AR139 29419
chemistryofaziri00clourich_Page_070thm.jpg
AR140 84671
chemistryofaziri00clourich_Page_071.QC.jpg
AR141 32321
chemistryofaziri00clourich_Page_071thm.jpg
AR142 84425
chemistryofaziri00clourich_Page_072.QC.jpg
AR143 31653
chemistryofaziri00clourich_Page_072thm.jpg
AR144 88182
chemistryofaziri00clourich_Page_073.QC.jpg
AR145 34629
chemistryofaziri00clourich_Page_073thm.jpg
AR146 94282
chemistryofaziri00clourich_Page_074.QC.jpg
AR147 34719
chemistryofaziri00clourich_Page_074thm.jpg
AR148 105667
chemistryofaziri00clourich_Page_075.QC.jpg
AR149 37750
chemistryofaziri00clourich_Page_075thm.jpg
AR150 102832
chemistryofaziri00clourich_Page_076.QC.jpg
AR151 36456
chemistryofaziri00clourich_Page_076thm.jpg
AR152 107393
chemistryofaziri00clourich_Page_077.QC.jpg
AR153 37824
chemistryofaziri00clourich_Page_077thm.jpg
AR154 102244
chemistryofaziri00clourich_Page_078.QC.jpg
AR155 36263
chemistryofaziri00clourich_Page_078thm.jpg
AR156 102849
chemistryofaziri00clourich_Page_079.QC.jpg
AR157 37308
chemistryofaziri00clourich_Page_079thm.jpg
AR158 104115
chemistryofaziri00clourich_Page_080.QC.jpg
AR159 36627
chemistryofaziri00clourich_Page_080thm.jpg
AR160 102469
chemistryofaziri00clourich_Page_081.QC.jpg
AR161 37465
chemistryofaziri00clourich_Page_081thm.jpg
AR162 91316
chemistryofaziri00clourich_Page_082.QC.jpg
AR163 33064
chemistryofaziri00clourich_Page_082thm.jpg
AR164 103871
chemistryofaziri00clourich_Page_083.QC.jpg
AR165 37577
chemistryofaziri00clourich_Page_083thm.jpg
AR166 91945
chemistryofaziri00clourich_Page_084.QC.jpg
AR167 33528
chemistryofaziri00clourich_Page_084thm.jpg
AR168 105524
chemistryofaziri00clourich_Page_085.QC.jpg
AR169 38102
chemistryofaziri00clourich_Page_085thm.jpg
AR170 93083
chemistryofaziri00clourich_Page_086.QC.jpg
AR171 35067
chemistryofaziri00clourich_Page_086thm.jpg
AR172 100548
chemistryofaziri00clourich_Page_087.QC.jpg
AR173 34800
chemistryofaziri00clourich_Page_087thm.jpg
AR174 92739
chemistryofaziri00clourich_Page_088.QC.jpg
AR175 33034
chemistryofaziri00clourich_Page_088thm.jpg
AR176 97660
chemistryofaziri00clourich_Page_089.QC.jpg
AR177 36446
chemistryofaziri00clourich_Page_089thm.jpg
AR178 111194
chemistryofaziri00clourich_Page_090.QC.jpg
AR179 38015
chemistryofaziri00clourich_Page_090thm.jpg
AR180 106011
chemistryofaziri00clourich_Page_091.QC.jpg
AR181 38180
chemistryofaziri00clourich_Page_091thm.jpg
AR182 108194
chemistryofaziri00clourich_Page_092.QC.jpg
AR183 38305
chemistryofaziri00clourich_Page_092thm.jpg
AR184 100282
chemistryofaziri00clourich_Page_093.QC.jpg
AR185 37900
chemistryofaziri00clourich_Page_093thm.jpg
AR186 90007
chemistryofaziri00clourich_Page_094.QC.jpg
AR187 33508
chemistryofaziri00clourich_Page_094thm.jpg
AR188 99645
chemistryofaziri00clourich_Page_095.QC.jpg
AR189 36101
chemistryofaziri00clourich_Page_095thm.jpg
AR190 110508
chemistryofaziri00clourich_Page_096.QC.jpg
AR191 37867
chemistryofaziri00clourich_Page_096thm.jpg
AR192 106785
chemistryofaziri00clourich_Page_097.QC.jpg
AR193 37115
chemistryofaziri00clourich_Page_097thm.jpg
AR194 110792
chemistryofaziri00clourich_Page_098.QC.jpg
AR195 38092
chemistryofaziri00clourich_Page_098thm.jpg
AR196 106939
chemistryofaziri00clourich_Page_099.QC.jpg
AR197 38404
chemistryofaziri00clourich_Page_099thm.jpg
AR198 101141
chemistryofaziri00clourich_Page_100.QC.jpg
AR199 35647
chemistryofaziri00clourich_Page_100thm.jpg
AR200 109669
chemistryofaziri00clourich_Page_101.QC.jpg
AR201 38381
chemistryofaziri00clourich_Page_101thm.jpg
AR202 92886
chemistryofaziri00clourich_Page_102.QC.jpg
AR203 34173
chemistryofaziri00clourich_Page_102thm.jpg
AR204 99385
chemistryofaziri00clourich_Page_103.QC.jpg
AR205 37042
chemistryofaziri00clourich_Page_103thm.jpg
AR206 61579
chemistryofaziri00clourich_Page_104.QC.jpg
AR207 23846
chemistryofaziri00clourich_Page_104thm.jpg
AR208 27714
chemistryofaziri00clourich_Page_105.QC.jpg
AR209 15597
chemistryofaziri00clourich_Page_105thm.jpg
AR210 48238
chemistryofaziri00clourich_Page_106.QC.jpg
AR211 21659
chemistryofaziri00clourich_Page_106thm.jpg
AR212 53739
chemistryofaziri00clourich_Page_107.QC.jpg
AR213 23871
chemistryofaziri00clourich_Page_107thm.jpg
AR214 50089
chemistryofaziri00clourich_Page_108.QC.jpg
AR215 22328
chemistryofaziri00clourich_Page_108thm.jpg
AR216 56958
chemistryofaziri00clourich_Page_109.QC.jpg
AR217 25015
chemistryofaziri00clourich_Page_109thm.jpg
AR218 59885
chemistryofaziri00clourich_Page_110.QC.jpg
AR219 25198
chemistryofaziri00clourich_Page_110thm.jpg
AR220 63792
chemistryofaziri00clourich_Page_111.QC.jpg
AR221 26251
chemistryofaziri00clourich_Page_111thm.jpg
AR222 55942
chemistryofaziri00clourich_Page_112.QC.jpg
AR223 24283
chemistryofaziri00clourich_Page_112thm.jpg
AR224 58300
chemistryofaziri00clourich_Page_113.QC.jpg
AR225 25020
chemistryofaziri00clourich_Page_113thm.jpg
AR226 43859
chemistryofaziri00clourich_Page_114.QC.jpg
AR227 21031
chemistryofaziri00clourich_Page_114thm.jpg
AR228 54499
chemistryofaziri00clourich_Page_115.QC.jpg
AR229 23592
chemistryofaziri00clourich_Page_115thm.jpg
AR230 44835
chemistryofaziri00clourich_Page_116.QC.jpg
AR231 21390
chemistryofaziri00clourich_Page_116thm.jpg
AR232 54164
chemistryofaziri00clourich_Page_117.QC.jpg
AR233 23829
chemistryofaziri00clourich_Page_117thm.jpg
AR234 50783
chemistryofaziri00clourich_Page_118.QC.jpg
AR235 22282
chemistryofaziri00clourich_Page_118thm.jpg
AR236 57371
chemistryofaziri00clourich_Page_119.QC.jpg
AR237 24531
chemistryofaziri00clourich_Page_119thm.jpg
AR238 49312
chemistryofaziri00clourich_Page_120.QC.jpg
AR239 22277
chemistryofaziri00clourich_Page_120thm.jpg
AR240 55552
chemistryofaziri00clourich_Page_121.QC.jpg
AR241 24663
chemistryofaziri00clourich_Page_121thm.jpg
AR242 91825
chemistryofaziri00clourich_Page_122.QC.jpg
AR243 34462
chemistryofaziri00clourich_Page_122thm.jpg
AR244 122409
chemistryofaziri00clourich_Page_123.QC.jpg
AR245 40585
chemistryofaziri00clourich_Page_123thm.jpg
AR246 122073
chemistryofaziri00clourich_Page_124.QC.jpg
AR247 38769
chemistryofaziri00clourich_Page_124thm.jpg
AR248 125646
chemistryofaziri00clourich_Page_125.QC.jpg
AR249 42076
chemistryofaziri00clourich_Page_125thm.jpg
AR250 118611
chemistryofaziri00clourich_Page_126.QC.jpg
AR251 40248
chemistryofaziri00clourich_Page_126thm.jpg
AR252 61899
chemistryofaziri00clourich_Page_127.QC.jpg
AR253 26210
chemistryofaziri00clourich_Page_127thm.jpg
AR254 66041
chemistryofaziri00clourich_Page_128.QC.jpg
AR255 26001
chemistryofaziri00clourich_Page_128thm.jpg
AR256 61438
chemistryofaziri00clourich_Page_129.QC.jpg
AR257 24762
chemistryofaziri00clourich_Page_129thm.jpg
AR258 26982
chemistryofaziri00clourich_Page_130.QC.jpg
AR259 15203
chemistryofaziri00clourich_Page_130thm.jpg
AR260 163962
UF00097753_00001.mets
METS:structMap STRUCT1 mixed
METS:div DMDID ORDER 0 main
D1 1 Main
P1 Page i
METS:fptr
P2 ii 2
P3 iii 3
P4 iv 4
P5 v 5
P6 vi 6
P7 vii 7
P8 viii 8
P9 ix 9
P10 x 10
P11 xi 11
P12 xii 12
P13 xiii 13
P14 xiv 14
P15 15
P16 16
P17 17
P18 18
P19 19
P20 20
P21 21
P22 22
P23 23
P24 24
P25 25
P26 26
P27 27
P28 28
P29 29
P30 30
P31 31
P32 32
P33 33
P34 34
P35 35
P36 36
P37 37
P38 38
P39 39
P40 40
P41 41
P42 42
P43 43
P44 44
P45 45
P46 46
P47 47
P48 48
P49 49
P50 50
P51 51
P52 52
P53 53
P54 54
P55 55
P56 56
P57 57
P58 58
P59 59
P60 60
P61 61
P62 62
P63 63
P64 64
P65 65
P66 66
P67 67
P68 68
P69 69
P70 70
P71 71
P72 72
P73 73
P74 74
P75 75
P76
P77 77
P78 78
P79 79
P80 80
P81 81
P82 82
P83 83
P84 84
P85 85
P86 86
P87
P88 88
P89 89
P90 90
P91 91
P92 92
P93 93
P94 94
P95 95
P96 96
P97 97
P98 98
P99 99
P100 100
P101 101
P102 102
P103 103
P104 104
P105 105
P106 106
P107 107
P108 108
P109 109
P110 110
P111 111
P112 112
P113 113
P114 114
P115 115
P116 116
P117 117
P118 118
P119 119
P120 120
P121 121
P122 122
P123 123
P124 124
P125 125
P126 126
P127 127
P128 128
P129
P130 130
METS:behaviorSec VIEWS Options available to the user for viewing this item
METS:behavior VIEW1 STRUCTID Default View
METS:mechanism Viewer JPEGs Procedure xlink:type simple xlink:title JPEG_Viewer()
VIEW2 Alternate
zoomable JPEG2000s JP2_Viewer()
VIEW3
Related image viewer shows thumbnails each Related_Image_Viewer()
INTERFACES Banners or interfaces which resource can appear under
INT1 Interface
UFDC_Interface_Loader



PAGE 1

CHEMISTRY OF AZIRIDINES By STUART CHANDLER CLOUGH A DISSERTATION PRESENTED TO THE GRADUATE COUNCIL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY UNIVERSITY OF FLORIDA 1969

PAGE 2

To M. L.

PAGE 3

ACKNOWLEDGEMENTS The author wishes to express his thanks to Dr. James A. Deyrup for suggesting this problem. His kind criticism and advice and his boundless enthusiasm and encouragement during the course of this work are greatly appreciated. The author would also like to thank the faculty, staff, and fellow graduate students of the University of Florida for making his stay in Gainesville not merely an educational experience but an extremely enjoyable one. Financial support by the National Aeronautics and Space Administration (1965-1968), the Graduate School of the University of Florida (19681969) and the National Science Foundation (1969) is gratefully acknowledged. iii

PAGE 4

TABLE OF CONTENTS Page No . ACKNOWLEDGEMENTS Ill LIST OF TABLES xii ABSTRACT xlii INTRODUCTION 1 CHAPTER I 6 REARRANGEMENTS OF 2-AZIRIDINECARBOXYLIC ACID HYDRAZIDES , 6 CHAPTER II 20 FORMATION AND REACTIVITY OF l-t-BUTYL-3-CHLORO-2AZETIDINONES 20 Formation of 3-Chloro-2-Azetidinones 20 Basic Hydrolysis of 3-Halo~2-Azetidinones kk CHAPTER III 50 PYROLYSIS OF TRIPHENYLMETHYL l-t-BUTYL-2AZIRIDINECARBOXYLATE 50 CHAPTER IV 58 EXPERIMENTAL 58 2,3-Dibroniobutyric Acid 59 2,3-Dibrcmobutyryl Chloride 59 Methyl 2,3-Dibromobutyrate 59 Methyl l-t-Butyl-2-Aziridinecarboxylate (5_) 60 Methyl l-3enzyl-2-Aziridi.necarboxylate (12) 60 Methyl l-Fhsnyl-2-Aziridinecarboxylate (J) ^0 iv

PAGE 5

CHAPTER IV (cont'd.) Page No EXPERIMENTAL (cont'd.) Methyl Cis-l-t-Butyl-3-Methyl-2-Aziridinecarboxylate (65) 6l Methyl Tran3 -l-t-Butyl-3-Methvl-2-Aziridinecarboxylate (66) 62 Reaction of l-t-Butyl-2-Aziridinecarboxylate (_5) With Hydrazine Hydrate in Ethanol 62 l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) . . . 63 l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (13) ... 63 l-Phenyl-2-Aziridinecarboxylic Acid Hydrazide (Ik) ... 6k l-Benzyl-2-Aziridinecarboxylic Acid HydrazideAcetone Hydrazone (15) 6k l-Phenyl-2-Aziridinecarboxylic Acid HydrazideAcetone Hydrazone (16) 65 Reaction of l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) With Water 65 3-t-Butylaminopropionic Acid (11) 66 Thermal Decomposition of l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) 66 Fragmentation of l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) in the Presence of Azobenzene ... 67 Thermal Decomposition of l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (13 ) in Water 67 3-Benzylaminopropionic acid (17) 68 Thermal Decomposition of l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (13) in Methanol 68 Methyl 3-Benzylaminopropionate (18) 69 v

PAGE 6

Page Ho . CHAPTER IV (cont'd.) EXPERIMENTAL (cont'd.) Fragmentation of l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (15 ) in the Presence of Azobenzene 69 3-Anilinopropionic Acid Hydrazide (8) 70 1,2-Diphenylaziridine (21 ) 70 l-t-Butyl-2-Aziridinecarbinol (22) 70 Ethyl Benzylaminoacetate 70 Benzylaminoacetic Acid Hydrazide (2_5.) 71 Anilinoacetic Acid Hydrazide (25) 71 1,2-Diphenylaziridine (21) -Stability to Hydrazine Hydrate 72 l-t-Butyl-2-Aziridinecarbinol (22) -Stability to Hydrazine Hydrate 72 Benzylaminoacetic Acid Hydrazide (25) -Stability to Methanol 72 Anilinoacetic Acid Hydrazide (2k) -Stability to Methanol 75 Ethyl p, P-Tetramethyleneglycidate 75 5,5-Tetramethylene-l4.-Hydroxy-5-Pyrazolidone 71). Sodium and Lithium l-t-Butyl-2-Aziridinecarboxylate (5_5. and ijj)) 74 Sodium C_is-l-t-Butyl-5-Methyl-2-Aziridinecarboxylate (67 ) 75 Sodium T rans -l-t-Butyl-5-Methyl-2Aziridlnecarboxylate (68) 75 vi

PAGE 7

Page N o. CHAPTER IV (cont'd.) EXPERIMENTAL (cont'd.) Triphenylmethyl l-t-Butyl-2-Aziridinecarboxylate (91 ) ... 75 Pyrolysis of Triphenylmethyl l-t-Butyl-2Aziridinecarboxylate (91 ) in Benzene 76 Thermal Decomposition of Triphenylmethyl l-t-Butyl-2-Aziridinecarboxylate (91) in Cume.ne 77 Pyrolysis of Triphenylmethyl l-t-Butyl-2Aziridinecarboxylate (91) in Benzene in the Presence of t-Butanol .78 Thermal Stability of l-t-Butyl-2Triphenylmethylaziridine (95) 78 Pyrolysis of Triphenylmethyl l-t-Butyl-2Aziridinecarboxylate (91) in Methanol 79 Methyl Triphenylmethyl Ether 79 Reaction of Lithium l-t-Butyl-2-Aziridinecarboxylate (k9) with Thionyl Chloride 80 Reaction of Sodium l-t-Butyl-2-Aziridinecarboxylate (5_2) with Oxalyl Chloride 81 Reaction of Sodium l-t-Butyl-2-Aziridinecarboxylate (55) with Oxalyl Chloride in the Presence of Triethylaraine 81 Reaction of Sodium Cis -l-t-Butyl-^-Methyl-2Aziridinecarboxylate (67) with Oxalyl Chloride 81 Reaction of Sodium Trans -l-t-Butyl-j-Me thy 1-2Aziridinecarboxylate (68 ) with Oxalyl Chloride 82 vii

PAGE 8

Pa^ejjo. CHAPTER IV (cont'd.) EXPERIMENTAL (cont'd.) Ring Expansion of Sodium l-t-Butyl-2-Aziridinecarbcxylate (5_3_) with Nosyl Chloride in Acetonitrile 85 Ring Expansion of Sodium Cis-l-t-Butyl-3-Kethyl-2Aziridinecarboxylate (67) with Nosyl Chloride in Acetonitrile 83 Reaction of Sodium Cis-l-t-Butyl-3-Methyl-2Aziridinecarboxylate (6j) with Nos yl Chloride .... Sk Cis-l-t~Butyl-3-Methyl-2-Aziridinecarboxylic Anhydride Q5) 8)+ Reaction of Cis-l-t-Butyl-3-Methyl-2-Aziridinecarboxylic Anhydride (JS) with Sodium Methoxide in Methanol in the Presence of Nosyl Chloride 85 Reaction of Sodium Trap s -l-t-Butyl-3-Me thy 1-2Aziridinecarboxylate (68) with Nosyl Chloride .... 83 Nmr of the Anhydrides in Sulfur Dioxide 86 Nmr Spectra of 3-Chloro-2-Azetidinones in Antimony Pentaf luoride-Sulfur Dioxide 87 Reduction of l-t-Butyl-3-Chloro-2-Azetidinone (50) with Zinc 87 l-t-Butyl-2-Azetidinone (51 ) 88 Reaction of l-t-Butyl-3-Chloro-2-Azetidinone (50) with Sodium Hydroxide 88 viii

PAGE 9

Pafte No. CHAPTER IV (cont'd.) EXPERIMENTAL (cont'd.) Reaction of l-t-Butyl-3-Cbloro-2-Azetidinone (50) with Sodium Methoxide 89 Reaction of Cis-l-t-Butyl-5-Chloro-U-Methyl-2Azetidinone (69 ) with Sodium Hydroxide 89 Reaction of Trans-l-t-Butyl-3-Chloro-l+-Methyl-2Azetidinone (70) with Sodium Hydroxide 90 SPECTRA Compound Solvent 1 Methyl Cis-l-t-Butyl-3-Methyl-2Aziridinecarboxylate (65) CC1, 93 2 Methyl Trans l-t-Butyl-3-Methyl-2Aziridinecarboxylate {6G) CC1, 93 3 Sodium Cis-l-t-Butyl-3-Methyl-2Aziridinecarboxylate (6 J) DO 93 k Sodium Trans1-t-Butyl3-Me thy 12-Aziridinecarboxylate (68) DO 95 5 l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) D^ 95 6 l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (1_3_) CDC1 95 7 l-Phenyl-2-Aziridinecarboxylic Acid Hydrazide (U) CDC1 97 ix

PAGE 10

Page No. SPECTRA (cont'd.) Compound 8 l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide-Acetone Hydrazone (15) 9 l-Phenyl-2-Aziridinecarboxylic Acid Hydrazide-Acetone Hydrazone (16 ) 10 Triphenylmethyl l-t-Butyl-2Aziridinecarboxylate (91 ) 11 l-t-Butyl-2-TriphenylroethylAziridine (95) 12 l-t-Butyl-3-Chloro-2Azetidinone (50) 13 l-t-Butyl-3-Chloro-2Azetidinone (50) 11+ l-t-Butyl-3-Chloro-2Azetidinone (50 ) 15 Cis-l-t-Butyl-3-Chloro-^Methyl-2-Azetidinone (69) 16 Cis-l-t-Butyl-3-Chloro-4Methyl-2-Azetidinone (69 ) 17 Cis-l-t-Butyl-3-Chloro-lj.Methyl-2-Azetidinone (69) 18 Trans1-t-Butyl3-Chloro-l+Methyl-2-Azetidinone (70) Solvent CDC1 97 CDC1 97 CDC1 99 CDC1 99 3 CC1. 99 k SO 101 SbF 5 *S0 101 CC1 101 so 2 103 sbF 5 -so 2 103 cci^ 103

PAGE 11

Page No. SPECTRA Compound Solvent 19 l-t-Butyl-2-Azetidinone (51) CC1 105 20 l-t-Butyl-2-Azirdinecarboxylic Anhydride (7^a) CC1. 105 21 Cis-l-t-Butyl->Methyl-2Aziridinecarboxylic Anhydride (75b) CC1 105 22 Cis-l-t-Butyl-l+-Methyl-lAzabicyclo [ 1.1.0.] Butane2-One Cation (Jit) SOg 107 23 Trans -1C-Butyl>Me thyl-2Aziridirecarboxylic Anhydride (JJc) CC1,. 107 2k Trans -1-t-Butyl-l^-Me thyl1Azabicyclo [1.1.0.] Butane2-One Cation Q5) S0 2 ...... 107 BIBLIOGKAPHY 108 BIOGRAPHICAL SKETCH 11^ xi

PAGE 12

LIST OF TABLES Table No. Page No . I Ring Strain Determined From Heats of Combustion 2 II Vicinal Coupling Constants of Aziridine and Azetidinone Ring Protons 5 III Ring Strain in Three-Membered Rings 28 IV Chemical Shifts (5) in Sulfur Dioxide Relative to External Tetramethylsilane in Carbon Tetrachloride 32 V Chemical Shifts (5) in Sulfur Dioxide Relative to External Tetramethylsilane in Carbon Tetrachloride 35 VI Chemical Shifts (6) Relative to External Tetramethylsilane in Carbon Tetrachloride .... kO VII Apparent Second Order Rate Constants for Hydrolysis (0.5 N NaOH/8570 Ethanol, 50) .... k5 xii

PAGE 13

Abstract of Dissertation Presented to the Graduate Council in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy CHEMISTRY OF AZIRIDINES By Stuart Chandler C lough August, 1969 Chairman: James A. Deyrup Major Department: Chemistry The unusual reactivity of some 2-aziridinecarboxylic acid derivatives has been investigated. In the course of this study several 1-substituted-2-aziridinecarboxylic acid hydrazides were prepared. The fragmentation of these hydrazides was studied and found to proceed with formation of diimide and ketene intermediates. The mechanistic implications of these results are discussed. The reaction of sodium l-t-butyl-2-aziridinecarboxylates with thionyl chloride, oxalyl chloride, and arylsulfonyl chlorides was found to give good yields of l-t-butyl-3-chloro-2-azetidinones. Stereochemical evidence and product studies suggest the intermediacy of a 1-azabicyclo[1.1.0.] butane-2-one cation in the ring expansion. This is confirmed by nmr studies of 2-aziridinecarboxylic anhydrides in sulfur dioxide. The synthetic utility of this ring expansion is discussed. The pyrolysis of triphenylmethyl l-t-butyl-2-aziridinecarboxylate was investigated as a possible route to a 2-azirine. The pyrolysis did xiii

PAGE 14

not generate the 2-azirine, but instead l-t-butyl-2-triphenylmethylaziridine and N-t-butyl-triphenylmethylmethylamine. The mechanism of this reaction is discussed. xiv

PAGE 15

INTRODUCTION The ultimate goal of the physical organic chemist is the complete understanding of the chemical and physical phenomena associated with all organic matter. The una tta inability of this goal forces the chemist to attempt the understanding of simple systems where, by theory and experiment, the frontiers of knowledge can systematically, albeit slowly, be extended. In this manner the concepts of radicals, ions, transition states, molecular orbitals, and the three-dimensional structure of molecules have been born. Reaction mechanisms for many reactions are now understood (or at least thought to be understood), and the effect of additional substituent groups on reaction rates in various systems can quantitatively be predicted with reasonable success. It has been shown that the presence of an unshared pair of electrons situated close to a reaction center in a molecule can enormously affect the rate, direction, and stereochemistry of the reaction. This propinquity effect, neighboring group participation, is quite dependent on the geometry 2 of the substrate. Another phenomenon known to dramatically affect the rate and direction of a reaction is ring strain. This is the extra free energy in a cyclic system which can be correlated with the unusual geometry of the molecular orbitals of small ring compounds. The concept of ring strain, first postulated by Adolph von Baeyer In 1885, has attracted considerable interest and undergone extensive refinement. The effects of ring strain are most

PAGE 16

2 apparent in ring closure and ring cleavage reactions, and they decrease with increasing ring size as one might expect. Generally heterocyclic rings are 4 not quite as strained as their analogous carbocyclic rings. TABLE I 4b c Ring Strain Determined From Heats of Combustion Compound

PAGE 17

The work done to date in this and other laboratories indicates that the electron pair on nitrogen is capable of participating in reactions both on and near the ring. Ring strain also seems to play a major role in the chemistry of this system, and ring cleavage is frequently observed. Three classes of 2-aziridinecarboxylic acid derivatives are discussed in this dissertation: 2-aziridinecarboxylic acid hydrazides, 2-aziridinecarboxylic acid salts, and triphenylmethyl l-t-butyl-2-aziridinecarboxylate. The chemistry of these compounds will be discussed separately in Chapters I, II, and III respectively. The syntheses of all of these compounds began with the syntheses of the appropriate methyl 2-aziridinecarboxylates. These esters were prepared using procedures patterned after those in the literature by treating the appropriate methyl 2,3-dibromopropionate with triethylamine followed by the appropriate primary amine. These reactions gave rather good yields of the aziridine esters. Et 3 N R^~tAoch, 2) R'NHg I ' In the formation of methyl l-t-butyl-3 _ methyl-2-aziridinecarboxylate two isomers were obtained. It was found that the choice of solvent determined which isomer predominated in the product mixture. When the reaction was run in methanol the ratio of cis to trans aziridine was about four to one. When excess t-butylamine was used as the solvent, the ratio of cis to trans aziridine was about three to five. Similar solvent effects have

PAGE 18

9 been observed before in Gabrieltype aziridine syntheses, and it was considered fortunate that this effect occurred here as it facilitated separation of the isomers. The cis isomer was obtained in a pure state by spinning band distillation of a mixture of the cis and trans isomers. The trans isomer was completely separated from the cis in the same manner, although at first it was not separated from a major impurity believed to be methyl t-butylaminoacetate. The impurity did not interfere with subsequent reactions however. A reasonable mechanism for its formation would involve acid catalyzed hydrolysis of the 1,3-dipole as shown below. V 5 — ± > ^flf^V 0CH 3_l^ » t-BuNHCH 2 C0 2 CH 3 I | H 2 c 2 3 t-Bu t-Bu Later it was fcund that if the crude aziridine ester was dissolved in benzene and washed with aqueous sodium carbonate prior to the distillation, this difficulty did not arise, and the trans ester was obtained analytically pure. The assignments of stereochemistry to the aziridines and azetidinones to be discussed in Chapter II were made on the basis of coupling constants observed in their nmr spectra. It has previously been shown that the vicinal coupling constants for protons cis to each other on the aziridine * Refer to Chapter III for a related hydrolysis of an aziridine 1,3-dipole. For an analogous acid catalyzed decomposition, see Reference 10.

PAGE 19

5 ring range between 5 and 8 Hz, but for protons trans to each other the coupling constants drop to between 2 and 5 Hz. Similarly cis coupling constants are larger than trans coupling constants in the azetidinone ring 12 in accord with the Karplus equation. Analysis of the nmr spectra of the aziridines and azetidinones prepared in this work gave the following values for the vicinal coupling constants (TABLE II) The cis stereochemistry was assigned to the isomer having the greater value. TABLE II Vicinal Coupling Constants of Aziridine and Azetidinone Ring Protons J . (Hz) J (Hz) Compound cis v ' trans "s^AoCHs 6.3 2.4 t-Bu CI ,0 5.1 1.7 I* 5 v CH 3 t-Bu C k /? 5.0 2.1 tf t-Bu

PAGE 20

CHAPTER I REARRANGEMENTS OF 2-AZIRIDINECARBOXYLIC ACID HYDRAZIDES 15 14 The generation of carbenoid (_1) and primary carbonium ion (2) centers on a carbon atom adjacent to the aziridine ring was the original goal of this work. The reactivity of these intermediates should yield considerable insight into the neighboring group effect of the aziridine ring. One synthetic route chosen for generating these species was the thermal decomposition of the tosylhydrazones Q) (Bamford-Stevens Reaction) of appropriate aziridinecarboxaldehydes. The proposed synNNHTs r-T^H \—/^ H V-Y
PAGE 21

s -^OC 2 H 5 H 2 NNH 2 >H 2 ^ ^% H NH I. TsCI 16% This route resulted in failure at the first step. When methyl l-t-butyl-2-aziridinecarboxylate (5) was treated with hydrazine hydrate according to normal procedures for the generation of carboxylic acid hy18 drazides, the only product isolated was 3-t-butylaminopropicnic acid hydrazide (6) (65%). V A CH 3 H 2 NNH g .H 2 t . BuNHC H 2 CH 2 C ^NHNH 2 i t Bu After this work was completed, Professor R. Huisgen pointed out that he had observed a similar reaction with methyl l-phenyl-2-aziridinecarboxylate (7) and hydrazine hydrate. ^A 0CH 3 H 9 NNHo-H,0 N' -± £_ ± — > C c H K NHCH o CH o C0NHNH o I 6 a Z d e C 6 H 5

PAGE 22

The only comment made by Huisgen concerning the mechanism of the reaction was as follows: "Fur diese interessante Hydrogenolyse des Aziridinringes •i 19 1st uns keine Analogie bekannt. Since the proposed route to the aziridinecarboxaldehyde was no longer promising and since the reductive ring scission was neither expected nor readily explained mechanistically, an investigation of the mechanism of the decomposition of the aziridinecarboxylic acid hydrazides was begun. When a slight excess of methyl l-t-butyl-2-aziridinecarboxylate (5_) was stirred at room temperature for 9.5 hours with hydrazine hydrate, analysis of the resulting solution (in DO) by nmr spectroscopy revealed formation of methanol and a slight change in the pattern and chemical shift of the characteristic three-proton aziridine ring multiplet. Although its instability precluded isolation, the new compound was assigned the structure of l-t-butyl-2-aziridinecarboxylic acid hydrazide (9). V7 ° CH3 H 2 NNH 2 -H 2 ^ANHNHg I I t-Bu t-Bu When crude hydrazide 9 was left at room temperature for four days, considerable gas evolution was observed, and a solid identified as l,2-di-3-t-butylaminopropionyl hydrazine (10) precipitated. Refluxing the hydrazide 9 in water produced 3-t-butylaminopropionic acid (11) as the only recoverable material.

PAGE 23

V^ » t-Bu [t-BuNHCH 2 CH 2 C0NH-] ; 10 NBuNHCH 2 CH 2 C0 2 H Because l-t-butyl-2-aziridinecarboxylic acid hydrazide (9) was so unstable, other aztridine hydrazides were sought in the hope that they might be isolable and thus more amenable to study. The reactions of methyl 1-benzyland l-phenyl-2-aziridinecarboxylates (12 and T) with hydrazine hydrate gave spectrally pure crystalline compounds identified as 1-benzyland l-phenyl-2-aziridinecarboxylic acid hydrazides (l^ and 14) respectively. These solids themselves were not very stable but could be kept under nitrogen in the refrigerator for extended periods of time. When dissolved in acetone they formed the corresponding acetone hydrazones (15 and JUS) . The hydrazones are stable crystalline compounds for which satisfactory elemental analyses were obtained.

PAGE 24

10 ^Ac-CH, H 2 NNH ? -H 2 ^—^NHNHo X r-y^NHN =( CH 2 C 6 H 5 CH 2 C 6 H 5 CH 2 C 6 H 5 12 13 15 ^7^0CH 3 H 2 NNH 2 -H 2 0^ ^AnhNH,, A ^ ^/^NHN^ i i i C 6 H 5 C 6 H 5 C 6 H 5 1 14 16 Although isolable, the hydrazides JJ> and Uj. behaved similarly to l-t-butyl-2-aziridinecarbcxylic acid hydrazide (9). The benzyl hydrazide (15 ) gave 3-benzylaminopropionic acid (17 ) when refluxed in water and methyl J-benzylaminopropionate (18) , identified as its hydrochloride (19), when refluxed in methanol. The phenyl hydrazide (lij.) , when refluxed with excess hydrazine hydrate in ethanol, ring oDened to form 3anilinopropionic acid hydrazide (8) . u H 2 V^7 NHNH 2 > C 6 H 5 CH 2 NHCH 2 CH 2 C0 2 H CH 2 C 6 H 5 ,7 13 \CH3OH C 6 H 5 CH 2 NHCH 2 CH 2 C0 2 CH 3 HCI > [CgHgC^N HgCHgCHgCOgCH^] CI IS 19

PAGE 25

11 A NUhI , H.NNH -H.O ^T NHNH 2 _2 2 z ) C 6 H 5 NHCH 2 CH 2 C0NHNH 2 1 C 6 H 5 Numerous mechanisms can be formulated which are capable of explaining the observed products. The first to be considered is a direct re* duction of the aziridine ring by either hydrazine or perhaps diimide derived from hydrazine. The intermediacy of diimide has been well established in reductions involving hydrazine. The reduction of symmetrical double bonds proceeds smoothly and stereospecif ically to give cis addition of hydrogen. The reaction is thought to be concerted, in20 volving a six-membered cyclic transition state (20). H. I + I — * 11= f > HI + 20 * Prior oxidation of hydrazine, possibly by air, would be necessary.

PAGE 26

12 In an analogous manner concerted reduction of the aziridine ring was also conceivable. Driving forces for the reduction would be relief of ring strain and formation of nitrogen. However, 1,2-diphenylaziridine (21) and l-t-butyl-2-aziridinecarbinol (22) were stable to hydrazine hydrate under the reaction conditions. ^-f 6 5 H 2 NNH 2 H 2 Zl > NO REACTION C 6 H 5 ^— T^OH H 2 NNH 2 H 2 i t-Bu NO REACTION 22 This result combined with the observation that aziridine hydrazides were isolated and then allowed to ring open rules out the possibility of direct ring scission by hydrazine. The role the aziridine ring plays in the reaction also deserves investigation. The observations that benzylaminoand anilinoacetic acid hydrazides (2J> and 24) are stable to the reaction conditions implies that the reactivity observed is not to be associated with a-amino acid hydrazides but indeed is in some way associated with the aziridine ring. It is pertinent too that cyclopropanecarboxylic acid hydrazide, the carbocyclic analog, is a stable compound, apparently not enjoying this reactivity. C H OH C_H K NHCH o C0NHNH o > NO REACTION bod d A 24

PAGE 27

13 CH, OH C 6 H 5 CH 2 NHCH 2 C0NHNH 2 . 2 > N0 REACTION 23 Careful inspection of the above data suggested that the aziridine hydrazide rearrangement might involve formation of diimide and an aminoketene intermediate. The aminoketene intermediate (25) nicely accounts for all of the amino acid derivatives observed as products of the re21 arrangement. RIWCH 2 CH = C = > RNHCH 2 CH 2 COX Formation of diimide accounts for the copious gas evolution observed. Diimide is an extremely unstable compound although it does have a finite lifetime as is evidenced by its isolation at low temperature followed 22 by decomposition on warming. Two pathways are available for thermal decomposition, both of which yield gaseous products. Reduction of a second mole of diimide to form hydrazine and nitrogen seems to be favored 23 over spontaneous decomposition into hydrogen and nitrogen. 2 HN=NH * H ? NNH + N 2 HN=NH » H 2 + N 2 Confirmatory evidence for the presence of diimide was in fact obtained by observing concomitant reduction of azobenzene (26) to hydrazobenzene (27) during the conversion of l-benzyl-2-aziridinecarboxylic acid hydrazide (15) to methyl 3-benzylaminopropionate (18) as well as in the conversion of l-butyl-2-aziridinecarboxylic acid hydrazide (j)) to 5-t-butylaminopropionic acid (_11) .

PAGE 28

14 *NHNH 2 CH,OH NT + _± > C 6 H 5 CH 2 NHCH 2 CH z C0 2 CH 3 + 0NHNH0 CH 2 C 6 H 5 26 |8 27 13 S *\ hJ H N H CH^OH S^/ 2 > t-BuWHCH 2 CH 2 C0 2 H + 0NHNH0 26 ii ai The fragmentation of a-substituted carboxylic acid hydrazides to ketenes and diiraide has been observed before. For example, Paulson and Stoye have studied the fragmentation of a-mesyl hydrazide 28 and observed * o the formation of a ketene at the relatively low temperature of 50 . «~\ Ms0 O^NH-NH-H S + HN^NH Q. — Q. Buyle has studied the base catalyzed fragmentation of mono-, di-, and tri27 chloracetic acid hydrazide hydrochlorides (29) . These two apparently * The temperatures generally required to pyrolyze^alkyl and aryl carboxylic acid hydrazides are on the order of 150-175

PAGE 29

15 undergo a Grob type fragmentation generating ketenes and diimide. Cf-CR^C.-NH-NH-H 29 •cr R \ -— ^ C=C = + HN>NH „ / There are number of detailed paths by which a 2-aziridinecarboxylic id hydrazide could fragment to form diimide and an aminoketene (25). *• y& . « c RNHCH 2 CH = C=0 + HN=NH 25 4" C HoN-NH HNjNH ^ RNHCH2-^<\ HNtNH 30 * These formulations are not intended to imply any necessarily concerted timing in the events leading from the hydrazides to the products.

PAGE 30

16 Mechanism C can tentatively be ruled out in view of the known course of 28 intramolecular aziridine and epoxide ring openings. Thus one would expect attack to occur at the J-position and not at the 2-position. Also, based on what is known about the chemistry of 1,2-diazetidinones, the suggested intermediate QO) should be stable under the reaction conditions. The 2,5-diazetidinones synthesized to date are generally substituted at the 1and 2-positions. They do decompose at elevated tem29 peratures, but to form isocyanates (32) and Schiff bases Ql) . Ar Ar, A r. «-K R^r' 31 32 The observation that the. cleavage is facilitated by electron withdrawing groups at the 1and 2-positions has been interpreted as evidence for a diradical intermediate (22) formed by rupture of the weak N-N bond. Ar Ar, r H R' 33 Since the postulated intermediate diazetidinones QO) do not have radical stabilizing groups at either the 1or 2-position, it is expected that this type of cleavage would not readily occur. Cleavage to form diazo and ketone intermediates has not been observed, and it seems reasonable that this would be an even higher energy process.

PAGE 31

17 The data available are not sufficient to distinguish between the first two mechanisms (A and B) , both of which are Grob type fragmentations. Although in non-hydrogen bonding solvents the hydrazides might be expected to exist in an intramolecular ly hydrogen bonded conformation such that fragmentation would readily proceed according to mechanism A, the solvents used here (i.e. , water, methanol, ethanol) might seriously affect the conformation assumed by the hydrazide. Because of this it is difficult to differentiate between the first two mechanisms. It would be possible to gain some insight via a kinetic investigation, but the hydrazides were never purified enough to make such a kinetic investigation feasible. A perhaps more interesting problem arises when this reaction is contrasted with the rearrangements of epoxy hydrazides. Martynov and 28a Belov allowed epoxy esters (34) to react with hydrazine and were unable to isolate the epoxy hydrazides Q5) . Instead, they obtained hydroxy pyrazolidones Q6) . The data which they presented was not considered sufficient proof of structure for the pyrazolidones however. Following their procedure, ethyl P, (3-tetramethyleneglycidate was heated with hydrazine hydrate. Nmr and mass spectroscopy verify the pyrazolidone structure of the crystalline product. The mechanism of this rearrangement presumably involves intramolecular nucleophilic attack at the 3-position of the epoxide ring (route A) . Initial attack of hydrazine at the 3-position to open to a hydrazine intermediate (37) followed by ring 32 (route B) closure to the pyrazolidone has also been suggested. The question remains, why do epoxy and aziridinecarboxylic acid hydrazides react so differently?

PAGE 32

18 NHNH< 37 The aziridinecarboxylic acid hydrazide decomposition also contrasts 28b remarkably with rearrangements of aziridine and epoxy hydrazones. Fadwa has shown that the tosylhydrazones of epoxy ketones Q8) rearrange to form ^-hydroxy pyrazolines (59) , and Cromwell et al. , have shown that phenyl hydrazones of aziridine ketones (kO) rearrange to form lj.-amino pyrazolines (kD . These rearrangements have been explained by postulating intramolecular nucleophilic attack at the 3-position of the heterocycle. H TsN. £ N T»x > N < 38 39 OH

PAGE 33

19 0NH 6 v^ "A" R NHR 40 41 Again, why does the aziridinecarboxylic acid hydrazide fail to rearrange by intramolecular attack at the 3-position to form an aminopyrazolidone? The nature of the heteroatom (0,N) probably does not play the major role in directing the course of the reactions since both epcxy and aziridine hydrazones undergo analogous rearrangements. The answer probably lies in steric and conformational effects which could be greatly affected by substituent groups on the ring and to a lesser extent by the heteroatom and groups on the heteroatom. There may be a fantastic frangiomeric effect facilitating fragmentation relative to intramolecular rearrangement of the aziridinecarboxylic acid hydrazides. In any case, it can be concluded here that 2-aziridinecarboxylic acid hydrazides do fragment to form aminoketenes and diimide. One important driving force is relief of ring strain. The reaction appears to be general for aziridines with various substituents on nitrogen (aryl and alkyl). The reaction may or may not find synthetic utility, but mechanistically it does deserve further investigation. Another problem deserving further attention is the original goal of this work generation of carbenoid and primary carbonium ion centers adjacent to the aziridine ring.

PAGE 34

CHAPTER II FORMATION AND REACTIVITY OF 1t-BUTYL-3-CHLORO-2-AZETIDINONES Formation of 5-Chloro-2-Azetidinones The 2-azetidinone ring was first successfully synthesized in 1907 when H. Staudinger observed that cyclization of diphenylketene (1+2) and benzaldehyde anil (Ifj ) yielded 1, 3,3,l».-tetraphenyl-2-azetidinone (hk) • 2 c=c=o 42 $CH»N0 43 44 Since that time 2-azetidinones (p-lactams) have attracted considerable interest as a reactive strained heterocyclic ring system and as a key part of biologically active cephalosporin (14-5) and penicillin (1+6) structures. Because of the biological activity of these systems, a variety of routes have been developed to generate the azetidinone ring, and some aspects of the chemistry of azetidinones have been investigated. Most of the research in this field has been carried out since World War II and includes the total synthesis of penicillins. 20 %

PAGE 35

21 t^l RNH rr C0 o H 45 46 This chapter will deal with the discovery that certain aziridine derivatives undergo ring expansion to 3-halo-2-azetidinones Q£Q . Some of the reactions characteristic of this heterocyclic ring will also be discussed. CI. Bu 47 This work btgan when an attempt to synthesize a 2-aziridinecarbonyl chloride (kS ) resulted in a new path to the 3-halo-2-azetidinone system. When lithium l-t-butyl-2-aziridinecarboxylate (lj-9) was treated with thionyl chloride in the pre3ence of excess sodium hydride, a 33% yield of 1-t" butyl-3-chloro-P-azetidinone (50 ) was obtained.

PAGE 36

22 ^A 1 I t-Bu 49 t-Bu 50 The structure of the azetidinone (50 ) was assigned on the basis of the nmr spectrum, a carbonyl absorption in the ir at 1760 cm (characteristic of the azetidinone ring), and a satisfactory elemental analysis. The mass spectrum showed parent ions at m/q 161 and 163 in the proper ratio for the chlorine isotopes as well as cleavage of the ring in both directions (a and b) as expected from published mass spectral studies of 2-azetidinones. 38 CH,« CI N: r

PAGE 37

23 Further proof of structure was obtained by reduction of j)0 to 1-t-butyl2-azetidinone (51) with zinc dust in refluxing ethanol, a procedure patterned after that of Knunyants and Gambaryan.^ 3 The same azetidinone was then synthesized in low yield from 3-t-butylaminopropionic acid (11) 39 and thionyl chloride. CI S *° Zn | f S0CI 2 i j » ' I < — t-BuNHCH2CH 2 C0 2 H 1 — N EtOH U ^ Et 3 N t-Bu t-Bu 50 5j U The ring expansion was considered to be of both mechanistic and synthetic interest, and thus further investigation of the reaction was initiated. Several mechanisms could reasonably account for the ring expansion. The first route to be considered was acid catalyzed ring opening of the aziridine to give an a-chloro-p-amino acid. This species might then react with thionyl chloride to form the amino acid chloride (52 ) which 39 could, in turn, ring close to the 2-azetidinone (50) . i t-Bu 49 ' 5 HCI -HCI C S—f° N' > t-BuNHCHoCHCICOCI > ' 1 S0CI 2 L N x j> ? t-Bu • 52

PAGE 38

2k Several observations make this route unlikely. The reaction with thionyl chloride was not inhibited by excess sodium hydride. The ring expansion also proceeded when sodium l-t-butyl-2-aziridinecarboxylate (53 ) was treated with oxalyl chloride, and the yield was not diminished when this reaction was rerun in the presence of triethylamine. ^-^ONa (C0CI) 2 C S f° (COCI) 2 ^-jAqHq . • L -N EUN t-Bu t-Bu 3 t-Bu 26% 29% 53 50 53 It is unlikely that acidic ring opening of the aziridine would occur under I4.O either of the above basic conditions. The second route to be considered involves transient formation of a six-membered heterocyclic intermediate (5Jj.) via mixed anhydride 5j>. Subsequent loss of sulfur dioxide from 51fc might generate the 2-azetidinone (50 ) A C /? C kJ^ Cl v A s-o~~ — * I L t-Bu {., /W N * Nbu t-Bu t-Bu 55 54 50

PAGE 39

25 Precedent for the ring contraction can be found in the pyrolysis of p-acylamino acids where formation of a six-membered cyclic intermediate (56) is postulated. 'OH 56 Attack by the annular nitrogen at sulfur finds some analogy in the formation and isolation of oxathiazolidine 5J in the reaction of aziridinol 22 with thionyl chloride. 1 * t-Bu 22 57 This mechanism, however, appears unlikely for several reasons. In the first place, the similar yields and products obtained with oxalyl chloride are suggestive of a common intermediate in both reactions. Secondly, the best available analogies (e.g. , 57 ) imply that _5Jt (as well as the unlikely seven-membered ring analog required by this mechanism for oxalyl chloride) would be stable under the mild conditions of the reaction. Finally, the ring expansion of 2-aziridinecarboxylic acid anhy-

PAGE 40

26 drldes to be. discussed below is also incompatible with a mechanism involving cyclic intermediates. A mechanism which is capable of explaining the results involves interaction of the unshared pair of electrons on the annular nitrogen and the carbonyl carbon resulting in formation of a 1-azabicyclo [1.1.0.]butane-2-one cation (58) . An examination of models suggests that the unshared pair of electrons on nitrogen is oriented favorably for overlap at the carbonyl carbon. Thus the bond deformations and additional strain * required for participation does not appear to be severe. The resulting cation 58 may then be captured at the 3-position by chloride to generate the chlorazetidinone according to the following scheme: i t-Bu CI :K 47 t-Bu CI ox t-Bu — X=S0CI, COCOCI * Analogous participation by nitrogen at a carbonyl carbon has been used to rationalize enhanced rates of hydrolysis of 7-amino esters 42

PAGE 41

27 Although this ion has no exact literature precedent, a number of 1azabicyclo [1.1.0.] butane cations have been postulated as reaction intermediates in ring expansions of aziridines to azetidines. In this laboratory solvolysis of aziridinecarbinyl tosylates (59) were found to give azetidinols (60) under certain conditions. This ring expansion is thought to involve a 1-azabicyclo [1.1.0.] butoniura ion (6l ) as an intermediate. 45 y" 0T8 ^ —*"°V N t-Bu t-Bu 59 61 60 W. Gensler and coworkers have shown that the reaction of labeled aziridinecarbinyl bromide 62 with aluminum chloride in benzene to form ring opened amine 6^ proceeds through an azetidine intermediate. It was suggested 44 that this might result from an azabicyclobutonium ion represented as 64. + * r -^Br AICI 3 # ^J SO 2 6 6 SO2 62 64 0SO 9 NHCH ? CH ? CH0, 63 S SO 2

PAGE 42

28 The stability of the azabicyclobutane ring has recently been demonstrated by the synthesis and isolation of 3~P n enyl-l-azabicyclo [1.1.0.]" lt-5 butane by Hortmann and coworkers. The introduction of a carbonyl group, as in 5_8, would be expected to cause an increase in strain. For example, Wiberg has shown that the introduction of a trigonal carbon in a threemembered ring results in approximately 13 kcal/mol additional strain energy (Table III). TABLE III Ring Strain in Three-Membered Rings Compound Strain Energy kcal/mol Cyclopropane 27.5 Methylenecyclopropane lj-1.0 Cyclopropene 53-1 This additional strain would increase the energy of the intermediate (58) , but would not preclude its formation. If the 1-azabicyclo [1.1.0.] butane-2-one cation (5 8) were actually involved in the ring expansion, the reaction should be stereospecif ic. Attack by chloride at the 3-position should occur at the back side of the C-N bond, i.e. , endo to the puckered ring. In order to test this hypothesis, the sodium salts of both cis and trans l-t-butyl-3-methyl2-aziridinecarboxylic acid (67 and 68) were prepared by stereospecif ic base catalyzed hydrolysis of the corresponding aziridine esters (65 and 66) . These salts were treated with oxalyl chloride in benzene, and the resulting ring expansions were indeed stereospecif ic. The cis aziridine

PAGE 43

29 (67J gave the cis azetidinone (69), and the trans aziridine (68) gave the trans azetidinone (70) as predicted. The reactions went in high yield and with no detectable (nmr) isomeric contamination. ^y^Na (C0CI) 2 CI V 79% CH 3\l— N s t-Bu t-Bu 67 69 CH ,'\. Ja (COCi) t-Bu 63 68 7C The stereospecificity of the ring expansion strongly supports tne intermediacy of the 1-azabicyclo [1.1.0.] butane-2-one cation (58 ) and unequivocally rules out the possibility of an a-carbonyl cation (71) t-Bu R X \ R' \ t-Bu t-Bu 71 * Elemental analysis of 69 did not check. However all spectral properties were in accord with the proposed structure. The mass spectrum was essentially identical to that of JO.

PAGE 44

50 It was hoped further evidence for the ionic mechanism could be obtained from reaction of the sodium aziridinecarboxylates (55 . 67 . and 68 ) with nosyl and tosyl chloride to form mixed anhydrides (72) . Mixed tosyl carboxylic acid anhydrides have been isolated, and there is precedent for their existence as reactive intermediates in some rearrange49 ments. Conceivably, participation at the carbonyl carbon by nitrogen might induce ionization of the mixed anhydride and thus lead again to the postulated bicyclic cations (58) . The resulting cations should be captured in the 3-position by nucleophiles to generate the 2-azetidinones as before. t-Bu R \ A ' * CI R' V N I cr H -r>^ o » r ,y— n f BU X R " Bu R R 72 58 47 Reaction of equivalent amounts of the sodium 2-aziridinecarboxylates (5^, 67, and 68) with nosyl or tosyl chloride did not yield the mixed anhydrides. Instead, mixtures of the sulfonyl chloride and the symmetrical aziridine anhydrides (75 ) were recovered. The symmetrical anhydride (75b) was formed free of nosyl chloride when two equivalents of the sodium salt were allowed to react with one equivalent of nosyl chloride. * Nosyl chloride was removed by fractional crystallization, leaving the anhydride (75b) behind.

PAGE 45

31 The structure of the anhydride is based on the nmr spectrum (CC1 -characteristic of the aziridine ring), and absorptions in the ir at 1820, and 1760 cm (characteristic of anhydrides). Chemical evidence for the anhydride structure was obtained by recovering both sodium 2-aziridine carboxylate (67) and methyl 2-aziridinecarboxylate (65, 35%) from the reaction of 75b with sodium methoxide in methanol. ;V-A)Na ArSQ 2 CI . "w^oV/" < I I t-Bu t-Bu t-Bu R= R = H 73 R = CH 3 i R = H 73 b R = H ; R=CH 3 73c Strong evidence for the bicyclic cation (58 ) was obtained from the nmr spectra of the aziridine anhydrides (75) in sulfur dioxide. A cold concentrated sulfur dioxide solution of the cis anhydride (75b) gave an nmr spectrum in accord with the anhydride structure. A more dilute solution, after standing at room temperature for a short time, gave an nmr spectrum with two sets of signals of similar pattern, one set at a chemical shift characteristic of the anhydride, and one set displaced downfield by an amount AS ppm (Table IV). Both the unionized aziridine anhydride and the aziridinecarboxylate anion are assigned as the species responsible for the upfield set of signals, and the bicyclic cation structure (7ifc) is assigned to the species responsible for the downfield set of signals (Table IV).

PAGE 46

32 TABLE IV Chemical Shifts (6) in Sulfur Dioxide Relative to External Tetramethylsilane in Carbon Tetrachloride Substrate v/° CH, N' I t-Bu \j I t-Bu 65 73b 74 A6 ppra t-Bu

PAGE 47

33 Addition of nosyl chloride or tosyl chloride to these solutions resulted in the disappearance of the upfield set of signals and enhancement of the downfield set of signals, presumably by ionization of the newly formed mixed anhydride (72) . \A ArSOoCI t-Bu Vt^oso 2 ai t-Bu 72 74 . The value of AS ppm (1.00) observed for the ring hydrogens of _7_k is quite similar to that observed by Olah (1.20) for 1-t-butylaziridinium ion in both antimony pentaf luoride-sulfur dioxide and acidic sulfur dioxide. The chemical shift of the t-butyl group (5 0.78) is not similar 52 to that observed by Olah aad Szilagyi (5 1.26). This discrepancy can be rationalized by differences in counterion, solvation and concentration effects, and anisotropic effects due to the bicyclic ring. Further chemical evidence for the bicyclic cation (Jj£) was obtained when the sulfur dioxide solutions were quenched with tetraethyl ammonium chloride in acetonitrile to stereospecif ically give ($9 . * Olah and Szilagyi observed differences in the chemical shifts of the same aziridinium ion of as much as 0.2 ppm with changes in [H ] and gegenion.

PAGE 48

CI CH 3 CN N ^~ N t-Bu 74 69 Similar results were obtained with the trans anhydride (75c) . A sulfur dioxide solution of the anhydride (75c ) in the presence of nosyl chloride initially showed two sets of signals attributable to the unionized anhydride and the carboxylate anion (upfield set of signals) and the bicyclic cation (75 ) (downfield set of signals), but decomposition was so rapid that the spectrum obtained was not at all satisfactory. At -20 a clean spectrum of the bicyclic cation was obtained. Again, values of 8 and A6 ppm for the tertiary butyl group and the ring hydrogens were in accord with expectations (Table V) . On warming, these signals disappeared with concomitant formation of a new set of signals attributable to trans -l-t-butyl-5-chloro-l+-methyl-2-azetidinone (70) .

PAGE 49

35 TABLE V Chemical Shifts (5) in Sulfur Dioxide Relative to External Tetramethylsilane in Carbon Tetrachloride Substrate t-Bu t-Bu I V^ 00 " 3 H^ 66 75 A5 t-Bu

PAGE 50

t-Bu t-Bu 73c t-Bu NsCI ^* «S ONs N' \ t-Bu t-Bu ^o^ so 2 , A H _^ CH. 7 5 CI CI tf t-Bu 7 The ring expansion of the anhydride could also be effected in acetonitrile. Good yields of 3-chloro-2-azetidinones were obtained when the aziridine anhydrides (7^a and 75b) and nosyl chloride were dissolved in a solution of excess tetraethyl ammonium chloride in acetonitrile. ' I Et 4 NCI R \J_' t ' Bu KBu cl r« \ o CH-aCN t^Bu R = H-, 7 3 Q 50 I 7 % R=CH 3 ; 73b 6 9 7 5 %

PAGE 51

37 It is pertinent to this discussion that, although acetonitrile is a well established carbonium ion trap, 3 no detectable amount of ionic intermediate was intercepted. This is in accord with the observations of Leonard that aziridinium ions do not react directly with acetonitrile. Ring opening of aziridinium ion iG to form a more stable carbonium ion occurs prior to reaction with acetonitrile. P ChUCN \*J 3 ) \ + r> N \-0 < CIO. CIOJ CIO, 76 The postulated intermediate (58 ) is, among other things, an aziridinium ion and thus would not be expected to react with acetonitrile. The ring expansion of the aziridine anhydrides convincingly rules out the possibility of any cyclic intermediate (5k) such as discussed previously. The direct observation of the bicyclic ions (7J£ and 21) in sulfur dioxide rules out any concerted geitonodesmic ring expansion of the anhydride.

PAGE 52

38 l t-Bu OK ,0 t-Bu The observed increase in yield of 2-azetidinone with methyl substitution at the 3-position in the reaction of the aziridine salts with oxalyl chloride is also not in accord with a geitonodesmic rearrangement. Civ .0

PAGE 53

59 58 CI, * t-Bu 47 R R CI \^° N' I t-Bu 77 It was thought that the 3-chloro-2-azetidinones might readily lend themselves to an nmr study in antimony pentaf luoride-sulfur dioxide solution. Alkyl halides; when dissolved in this solution, ioni?
PAGE 54

ko antimony pentaf luoride solutions, but little change in the splitting pattern was noted. Similar results were obtained with cis -l-t-butyl-5chloro-4-methyl-2-azetidinone (69) . The spectra of the antimony pentaf luoride solutions are quite different from the sulfur dioxide spectra of the same supposed ions generated from the anhydride presursors. The changes in the chemical shift (A5 ppm) are real and are reasonable for * what one might expect for ammonium ion formation. In fact, they are greater than the values of AS ppm observed for triethyl amine and tetraethyl ammonium chloride, a model system which neglects all anisotropic effects of the bicylic rings (Table VI). Chemical Shifts (5) Relative to External Tetramethylsilane in Carbon Tetrachloride Compound R S0 g S0 2 «SbF 5 A5 ppm t-Bu 0.75 1.15 0.1*0 H C, \ fP He 4.08 If. 89 0.81 H b> — N Hb 3.18 4.02 0.84 H/ N t-Bu Ha 2.70 3-59 0.89 * For hydrogens two carbons removed from a cation center shifts of 0.8-1.8 ppm are common. °

PAGE 55

kl TABLE VI (cont'd) j. Compound R S0 2 StySbF,. A6 ppm t-Bu 0.76 1.08 0.32 Civ H b ^ f Hb ^-22 4.95 0.73 Ha 3.56 4.37 0.81 it! CH 3 > Ha' ^t-Bu EtJ Et.NCl CH 0.80 1.25 0.45 CH 2 0.50 CH 2 2.08 CH 0.69 0.19 CH 2 2.65 0.57 However, when attempts were made to quench these supposed ions with 59 methanol according to procedures used by Olah to quench similarly formed carbonium ions, only the original chloroazetidinones could be recovered. These results are interpreted as indicating donor-acceptor complex formation, probably either with oxygen and/or nitrogen and antimony pentafluoride, but not ionization.

PAGE 56

1)2 t-Su },+ SbF s Cl' l-Bu 'ep. .sbF. N-Bu DONOR-ACCEPTOR COMPLEX It is not surprising that ionization of the chloroazetidinones Q±T) fails to occur. Diazonium ion T]i recently has been generated in the cephalosporin series. This ion, in the presence of chloride, undergoes a displacement to form the chlorocephalosporin (79 ) . The observed inversion of configuration suggests that the reaction of 78 does not proceed by loss of nitrogen to give the bicyclic ion (80) . Formation and capture of 80 would require retention of configuration. J-M^ch. cr y~ N-s^, 'CH 2 0Ac C0 2 CH 3 C0 2 CH 3 ^i , "^ s CH 2 0Ac C0 2 CH 3 80 + The reluctance of the }-substituted-2-azetidinones to ionize to the bicyclic cations can be rationalized on stereochemical grounds. An examination of crude models shows that the unshared pair of electrons on nitrogen is

PAGE 57

t3 not oriented favorably for overlap at the incipient cation center. Considerable bond deformation, and nance strain, is required for participation and thus ionization to occur. Furthermore, the planar ami da linkage would presumably inhibit such a deformation. Formation of bicyclic cations (58 ) is in contrast to the ionization of the tosyl a-amino acid anhydride (81) described by Sheehan and Frankenfeld. In that system fragmentation occurred to give the tosylate anion, a Schiff base (82) , and carbon monoxide, presumably vjU participation of the electron pair on nitrogen* loC-C Oo Z I NH0 TsCI Py 02 N-H I OTs * £ 2 CrN + C0 + " 0Ts 82 61 The analogous reaction in the aziridine system would have generated the azirinium ion (85 ) • Although such cations are known, they are greatly destabilized by ring strain. r-yC^OTs t-Bu i t-Bu CO OTs 83 * The mixed anhydride (81 ) was not isolated.

PAGE 58

I* Attempts have been made to extend the ring expansion to aziridines with other substituents on nitrogen, but to no avail. Nevertheless, hope still remains that suitable conditions will be found to make this reaction more general and synthetically useful. The potential biochemical utility of the 2-azetidinones makes such a stereospecif ic synthesis quite valuable. No attempt has been made to extend the ring expansion to other heterocyclic rings. However the possibility of such extension is considered to be a matter of both synthetic and mechanistic interest. Basic Hydrolysis of 5-Halo-2-Azetidinones Basic hydrolysis of 2-azetidinones generally leads to high yields of 0-amino acids. These reactions have received considerable attention 6k in the literature. A. D. Holley has found that the rate of hydrolysis is very much a function of the substituents on the ring, and it is presumed that this effect is the result of a combination of steric and inductive effects. As one might predict from strain arguments, the rates of hydrolysis for 2-azetidinones are greater than those for pyrrolidones, which in turn are greater than those for N-methylacetamide.

PAGE 59

45 TABLE VII Apparent Second Order Rate Constants for Hydrolysis * 4 " (0.5 N NaOH/857. Ethanol, 50) Compound 10 ,0 a a \^0 ^v: 10 TCg (liter/mole/sec) 15.0 1.0 O.k CH3CONHCH3 0.03 Basic hydrolysis of the 3-chloro-2-azetidinones (1+6 ) led not to the amino acids, but to the aziridinecarboxylic acid systems. 1-tButyl-3-chloro-2-azetidinone (50) gave good yields of sodium 1-t-butyi2-aziridinecarboxylate (52 ) and methyl l-t-butyl-2-aziridinecarboxylate (5) when treated with aqueous sodium hydroxide and with methanolic sodium methoxide respectively.

PAGE 60

k6 CI ,Q N u t-Bu 50 VIT/ONo t-Bu 52 VT/ OCHN I t-Bu Similar ring contractions have been observed in the analogous carbo67 cyclic system. For example, Conia and Ripoll 'have treated a-bromocyclobutanone (81+) with aqueous sodium carbonate and with sodium amide in 66 liquid ammonia and recovered cyclopropanecarboxylic acid (85) and cyclo67 propanecarboxamide (86) , respectively. v A ° H 85 NH* OS The mechanism proposed for these ring contractions involves initial attack of the base at the carbonyl carbon, followed by what is probably a concerted ring contraction giving the observed products. The reaction is stereospecif ic as one might predict. Trans -2-bromo5t-butylcyclo-

PAGE 61

hi butanone (87) when treated with aqueous sodium carbonate gives an approximately quantitative yield of Jtrans-2-t-butylcyclopropanecarboxylic acid (88). 66 JZf° S£* pf 0H -^LTN^oh " Br t-Bu CBr t b u g 8J A mechanism similar to the above might be involved in the ring contraction of the 3-chloro-2-azetidinones. Attack of base at the carbonyl carbon probably occurs prior to ring contraction. No evidence is available which can unequivocally distinguish between a concerted or a nonconcerted ring contraction step. The ring contraction is stereospecific however. Cis -l-t-butyl-^-chloro-lj.-methyl-2-azetidinona (69) on treatment with sodium hydroxide in aqueous dioxane gave clean sodium cis -l-t-butyl-5-methyl-2-aziridinecarboxylate ( 67) . Similarly, trans l-t-butyl-3-chloro-lj.-methyl-2-azetidinone (70 ) gave the trans aziridine sodium salt (68) on treatment with base. In the latter case the reaction was not at all clean. The structures of the other products of the reaction (which comprise about 50% of the recovered material) were not determined, and thus it cannot be said with certainty that none of the cis salt (66) was formed. In spite of this it does follow that the ring contraction is stereospecif ic.

PAGE 62

48 ch 3 nL_ n I ONa t-Bu t-Bu 69 67 Civ x.O n NoOH /V7 ONa CH 3 ' \. Bl <" Bu 10 68 A dramatic difference was noted in the rates of hydrolysis of the various chlosazetidinones. No quantitative rate data are available, but it can be said that the l4.-methyl-3-chloro-2-azetidinones hydrolyzed at a slower rate than the unsubstituted chloroazetidinone (20 vs 2 hr for complete reaction at reflux temperature). It is suspected that this difference is due to a similar combination of steric and electronic effects which plays so important a role in the hydrolysis of the azetidinones studies by Holley and Holley. It might even be suggested that the rate controlling step of the ring contraction is hydrolysis to give the a-chloro-p-araino acid (89 ) which under the basic conditions employed ring closes stereospecif ically 7 to give the aziridine (Gabriel Synthesis). This might also explain the mixture of products observed for the ring contraction of trans 1-t-butyl3-chloro-lj.-methyl-2-azetidinone. The intermediate amino acid (89 ) could conceivably lead to several products.

PAGE 63

ks v-r oH " , v-r oH 1 R^ JL\—f x0 ~ < t>BuNHCHRCHCIC0 2 i t-Bu 89 The ring contraction does suggest the possibility of a synthetically useful stereospecific route to the aziridine system. Extension of the reaction to azetidinones with different substituents, for instance aryl substituents, has not yet been attempted.

PAGE 64

CHAPTER III PYROLYSIS OF TRIPHENYLMETHYL l-t-BUTYL-2-AZIRIDINECARBOXYLATE One of the more theoretically intriguing and yet still more elusive systems waiting to be synthesized is the 2-azirine system (90 ) . It has been suggested that this cyclic class of compounds with potentially 69 four pi electrons could be antiaromatic. For this reason it might be expected to exhibit some rather interesting properties. A few un7 70 substantiated claims for 2-azirines can be found in the literature, but an authentic 2-azirine has yet to be isolated. I R 90 The hope of generating and studying a 2-azirine was the driving force behind the investigation of the pyrolysis of triphenylmethyl l-t-butyl-2-aziridinecarboxylate (91) . It was thought that heating this ester in a suitable solvent might induce ionization to form the triphenylmethyl cation and the carboxylate anion (92) . Since the triphenylmethyl cation has been shown to be an effective hydride ion abstracting agent for hydrogen atoms a to the nitrogen in alkyl 71 amines, it was hoped that hydride ion abstraction from the 3-position of the aziridinecarboxylate anion by the triphenylmethyl cation 50

PAGE 65

51 generated in situ would occur with simultaneous or subsequent decarboxylation to produce the first member (95) of the long-sought 2azirine system. With luck, this could be trapped with a diene to form a Diels-Alder adduct (9k) 72 I t-Bu 91 N-t-Bu f•C0. » W t " Bu 92 -C0 2 ,3 CH I t-Bu 93 It might be noted that this proposed decarboxylation is quite analogous to the decarboxylation in acetone of the anion of cinnamic acid dibromide, an apparently trans E 2 elimination. 7 3 'Wi •"» 8r .Br + C02 Triphenylmethyl esters of aziridine acids had not previously been prepared. Fortunately, published procedures for the formation of other triphenylmethyl esters from the sodium salts of the acids proved satisfactory. Reaction of sodium l-t-butyl-2-aziridinecarboxylate (52 ) with triphenylmethyl bromide in benzene gave the desired triphenylmethyl l-t-butyl-2-aziridinecarboxylate (91) in a reasonable yield.

PAGE 66

52 This ester was a solid and was quite stable when in a pure state. t-Bu C 6 H 6 f-Bu 52 9J The ester (91) was heated in a sealed tube in benzene at 180+ 10 for fourteen hours „ When the tube was cooled and opened, a noticeable amount of pressure was released, suggestive of gas evolution (decarboxylation). Two major components, representing about 90% of the reaction were recovered from the reaction mixture and characterized as l-t-butyl-2-triphenylraethylaziridine (95, 57%) and N-t-butyltriphenylmethylmethylamine (96, 53%) • *n' y3 * x n' + t-BuNHCH 2 c<0 3 t-Bu 6 6 t-Bu 91 95 M These products were not suggestive of 2-azirine formation. Nevertheless the problem of the mechanism of formation of both products was considered intriguing. Several routes for decarboxylation to the triphenylraethylaziridine are possible, one radical (A) and two ionic (B and C) . Formation of the amine (96) was unclear. . A control experiment showed that the triphenylmethylaziridine (95) was stable to the

PAGE 67

53 reaction conditions and thus is not the source of the amine (96) •C0 3 ^N 7 ' C0 2 x t-Bu )^ -c0 3 <._ 7 Aoc0 3 rV C03 I I T I t-Bu t-Bu t-Bu ^v +C0, ^^ V^7 co 2 1 t-Bu Decarboxylation of triphenylmethyl esters via a radical path has been suggested before although the data presented did not serve to 75 unequivocally demonstrate the existence of radicals. The possibility of a radical path in this aziridine system was investigated by carrying out the pyrolysis in cumene, a known and effective radical trap. Radicals abstract a hydrogen atom from cumene to form a cumyl radical which then couples with another similarly formed cumyl radical to form dicumyl (97 ) . Thus the presence of dicumyl is evidence for the 76 presence of radicals. 5 + rh -^o+k^> 97

PAGE 68

51* Conversely, the absence of dicumyl suggests that radicals are not present. Nevertheless it is conceivable that cage recombination of the radicals is so efficient that intervention of the radical scavang77 ing cumene cannot occur. The pyrolysis in cumene gave a practically identical product distribution as pyrolysis in benzene, and no detectable dicumyl was formed. Analysis for dicumyl was done by gas chromatography, and it was estimated that as little as 1% of the theoretical amount of dicumyl would be detected. Thus the radical mechanism was deemed unlikely. Studies of the decarboxylation of carboxylic acids indicate that generally decarboxylation occurs to form the carbanion. The reaction is facilitated by groups which stabilize the carbanion centers, for instance electronegative heteroatoms. No example of carbonium ion 78 formation via decarboxylation of carboxylic acids is known. RC0 2 H * R" + C0 2 + H Thus it might be expected that decarboxylation of the ester (91) is occurring via ionization to the triphenylmethyl cation, followed by decarboxylation to form the aziridine carbanion (Path C) . The problem was to experimentally verify this prediction. It was thought that a distinction between the two ionic paths (B and C) might be made via a trapping experiment. For this reason the triphenylmethyl ester (91) was pyrolyzed in methanol. It was predicted that methanol would intercept the carbonium ion to form a methyl ether. The carbanion should pick up a proton. After pyrolysis methyl

PAGE 69

55 triphenylmethyl ether was recovered, indicating that ionization to give the triphenylmethyl carbonium ion had occurred. Unfortunately no other species were recovered from the complex reaction mixture. I CH-OH t-Bu 3 9! 3 COCH 3 + Since no aziridine fragment was recovered, and since the change in the solvent was so drastic, it is not valid to claim that the decarboxylation occurs necessarily by path C merely on the basis of this experiment. It is felt that formation of methyl triphenylmethyl ether is at least supporting evidence for ionization as indicated in path C. Addition of a proton source to the reaction medium should allow capture of the carbanion to give either tr ip he nylme thane (path B) or 1-t-butylaziridine (path C) . t-Butanol was chosen as the proton source because, although it was capable of protonating the carbanion, it is not a good enough nucleophile to cause transesterif ication or hydrolysis of the triphenylmethyl ester. Pyrolysis in benzene in the presence of one equivalent of t-butanol resulted in a clean reaction yielding the triphenylmethylaziridine (95, 11%) and N-t-butyl triphenylmethylmethylamine (96, 88%) . In addition, when the benzene solution of the reaction mixture was washed with water and the water wash treated with dimedone reagent, the solid dimedone derivative (98) of formaldehyde 79 was recovered.

PAGE 70

56 ^OC0 3 t-BuOH > ^H + t . BuNHC H 2 c^ * HgC-O I CrMcI t-Bu 6 6 t-Bu 96 91 95 Although this experiment did not serve to differentiate between the two ionic routes to the triphenylmethylaziridine, it did suggest an explanation for the formation of the secondary amine, which in turn sheds much light on this system. A most reasonable mechanism for the formation of N-t-butyl triphenylmethylmethylaoiine (96) involves formation of a 1,3-dipolar species (99) . There are numerous examples where the aziridine ring opens to form a 80 1,3-dipolar species in this sense. When protons are present in the * system this dipolar species can be protonated to give the iminium cation * Precedent for protonation of an aziridine 1,3-dipole is claimed in the reaction of ethyl trans -1 , 3-diphenyl-2-aziridinecarboxylate (i) with t-butylisonitrile in acidic carbon tetrachloride to give a ketenimine (ii) ; J. A. Deyrup, to be published. iA^7 0C 2 H 5 "uNsC , *1 * — — > ^C-NCH 2 C0 2 C 2 H 5 H + t-BuN* ii

PAGE 71

57 81 (100) • Because of the positive charge on the nitrogen this ion should 78 decarboxylate readily via an ionic route to give a new iminium ion (101) . Hydrolysis of this ion would generate the amine _105 and formaldehyde, the observed products. If the dipolar species (99) i3 in equilibrium with the ester, the triphenylmethylaziridine (95) arises from the ester, and the amine (96 ) and formaldehyde arise from the 1,3dipole as suggested, the addition of t-butanol would tend to intercept the dipolar species and give the observed product distribution. OC0; t-Bu I 91 V C0 3 t-Bu 95 ^xyoc» 3 H * ; Mxv t-Bu 99 OC0, 9fi ' t-8u 100 -C0 C H?0 ^ + y\ . H 2 C=0 + t-BuNHCH 2 C0 3 *— x N^C0 3 t-Bu 101 If the decarboxylation yielding the triphenylmethylaziridine (95) is indeed proceeding via an aziridine carbanion, as is postulated here, it should be possible to generate analogous aziridine carbanions by other routes. If such procedures can be worked out they should be valuable as still another route to variously substituted aziridines.

PAGE 72

CHAPTER IV EXPERIMENTAL The melting points were determined on a Thomas Hoover Capillary Melting Point Apparatus and are uncorrected. Boiling points are recorded as the temperature at which the material distills, are at atmospheric pressure unless otherwise noted, and are uncorrected. Evaporative distillations were performed on small samples of material 8? following the (Kugelrohr) procedure of Graeve and Wahl. The infra-red spectra were recorded on a Perkin-Elmer instrument, Model number 137. The routine nmr spectra were recorded on a Varian Associates A60-A 60 megacycle recording spectrometer. The nmr data are presented * as follows: chemical shift (splitting pattern, number of hydrogens, coupling constant, assignment) . Chemical shifts are expressed in parts per million and in carbon tetrachloride and chloroform are relative to internal tetramethylsilane. In deuterium oxide chemical shifts are 1+0 relative to a position 1+.99 ppm upfield from the DOH signal. In sulfur dioxide chemical shifts are relative to external tetramethylsilane in carbon tetrachloride. * s = singlet; d doublet; dd = doublet of doublets; t = triplet; q = quartet; m = multiplet. 58

PAGE 73

59 Molecular weights were determined by mass spectrometry. The mass spectra were recorded on a RMU 6E mass spectrometer at 70 ev. The fragments are reported as m/e (relative intensity). Microanalyses were performed by Galbraith Laboratories, Inc., Knoxville, Tennessee, and by Peninsula Chemre search, Gainesville, Florida. 2.5-Dibromobutyric Acid This was prepared according to the procedure of Michael and Norton. 85 2,5-Dibromobutyrvl Chloride Thionyl chloride (130 g, 1.1 mol) was added to 2,3-dibromobutyric acid (181 g, 0.74 mol) and the resulting solution was gently refluxed for three hours. Distillation yielded 167 g (86%) of the acid chloride: bp 95-100 (20 mm) [Lit. 112° (20 mm)]; 81 * nmr (CC1 ) 8 1.95 (d, 3, J = 6 Hz, CH J, and k.h9 (m,2, CHBrCHBr) . Methyl 2.5 Dibromobutyrate 2,3-Dibromobutyryl chloride (I67 g, 0.635 mol) was added slowly to methanol (32 g, 1.0 mol) at room temperature with stirring. After ten minutes, excess methanol and hydrochloric acid were removed by rotary evaporation, and the residual oil was distilled to give 158 g (96%) of methyl 2,3-dibromobutyrate: bp 103-106° (17mm) [Lit. 125° (48 mm)]; 81 * nmr (CCl^) 8 1.90 (m, 3, CH ) , 3. 80 (s, 3, OCH ) , and 4-38 (m, 2, CHBrCHBr).

PAGE 74

60 Methyl l-t-Butyl-2-Aziridinecarboxylate (5) ko This was prepared according to the procedure of C. L. Moyer. Methyl l-Benzyl-2-Aziridinecarboxylate (12) Methyl 2,3-dibromopropionate (39.0 g, 0.15 mol) was dissolved in benzene (300 ml) in a three-necked flask equipped with an overhead stirrer, dropping funnel, and condenser, and the flask was immersed in an ice bath. Triethylamine (1+5 g, 0.1+5 mol) was added in a dropwise fashion followed by benzylamine (16 g, 0.15 mol). The reaction mixture was re fluxed overnight, then cooled to room temperature, and the solid amine hydrobromides were removed by filtration. Distillation of the thick oil left after evaporation of the filtrate gave 22.7 g (79%) °f methyl l-benzyl-2-aziridinecarboxylate (12): bp 90-95 (0.3mm) [Lit. 133° (5mm)]; 85 ir (liquid film) 1745 (C =0), 753, and 696 cm" 1 (phenyl) nmr (CC1.) 6 1-50 (dd, 1, ring proton), 2.02 (m, 2, ring protons), 3. 1+1 (q, 2, tfCHg), 3.56 (s, 3, 0CH 5 ), and 7.20 (s, 5, C^) . N0 2 : C, 69.09; H, 6.85; N, ' Found: C, 69.08; H, 7.03; N, 7.20. Anal . Calcd for C U H 15 N0 2 : c » 69.09; H, 6.85; N, 7.32. Methyl l-Phenyl-2-Aziridinecarbox y late (7) Methyl 2,3-diDromopropionate (71+ g, 0.28 mol) was dissolved in benzene (200 ml) and cooled in an ice bath. Triethylamine (63 g» 0.7 mol) was added dropwise to the stirred solution as triethylamine hydrobroraide precipitated. Then aniline (28 g, 0-3 mol) was added,

PAGE 75

61 and the reaction mixture was refluxed gently for 12 hours. The amine hydrobromides were removed by filtration, and the crude oil left after evaporation was distilled to give 3^-6 g (69%) of methyl l-phenyl-2aziridinecarboxylate (J) ' b P 92-100° (0.5 mm) [Lit. 95-105° (0.5 nan)]; 19 ir (liquid film) 1750 (C = 0) , f5k, and 695 cm" 1 (phenyl) ; nrar (CC1 } ) 5 2.1 (dd, 1, ring proton), 2.6 (m, 2, ring protons), 3.62 (s, 3, 0CH 3 ), and 7.0 (m, 5, C^) Found: C, 67-73; H, 6.35; N, 7.86. Anal . Calcd for C^H^O^ C, 67-78; H, 6.26; N, 7. 90. Methyl Cis -1-t-ButylVMethyl-2-Aziridinecarboxylate (65 ) Methyl 2, 3-dibromobutyrate (100 g, 0-38 mol) , triethylamine (100 g, 0.96 mol), and methanol (1*00 ml) were stirred at room temperature for three hours. t-Butylamine (70 g, 0.96 mol) was added, and the mixture was allowed to stand at room temperature for two days. Water was added, and the solution was extracted two times with benzene, dried (MgSO ) , and evaporated to an oil which on distillation gave 50 g (78%) of a mixture of cis -l-t-butyl-3-methyl-2-aziridinecarboxylate (65 , 85%) and trans l-t-butyl-3-methyl-2-aziridinecarboxylate ( 66, 15%). The pure cis isomer was obtained by spinning band distillation: bp 65 (3.0 mm); ir (liquid film) 2900 (CH) and 1750 cm" 1 (C = 0) ; nmr (CCl^; spectrum No 1) 6 0.95 (s, 9, t-butyl) , 1.17 (d, 3, J = 5.3 Hz, CH^) , 2.05 (m, 2, CHCH), and 3.65 (s, 3, OCH.,) ; molecular weight 171. Anal . Calcd for C g H Ncy C, 63-13; K, 10.01; N, 8.18. Found: C, 63-03; H, 9.99; N, 7.95.

PAGE 76

62 Methyl Trans-l-t-Butyl-5-Methyl-2-A zi cidlnecarboxylate (66) Methyl 2,3-dibromobutyrate (26 g, 0.10 mol) and trie thy lamine (39 g, 0.015 mol) were dissolved in benzene (50 ml) and left at room temperature overnight. The amine hydrobromides were removed by filtration, and the filtrate was evaporated to an oil. The oil was dissolved in t-butylamine (18.2 g, 0.25 mol) and left at room temperature for four days. The amine hydrobromides were removed by filtration, and the filtrate was evaporated to an oil which on distillation gave 12.14g (72%) of a mixture of cis-Q3%) and t rans (67%) methyl 1-tbutyl-3 _ methyl-2-aziridinecarboxylate. The trans isomer (.66) was, after washing with aqueous sodium carbonate, completely separated from the cJLs isomer by spinning band distillation: bp 65 (0.2 mm); ir (liquid film) 2950 (CH) and 1730 cm" 1 (C =0); nror (CC1 ; spectrum No 2) 6 1.10 (s, 9, t-butyl), 1.26 (d, 3, J = 5.5 Hz, CH ) , 2.13 (d, 1, J = 2.k Hz, CgH), 2.46 (m, 1, C H), 3.63 (s, 3, OCH ) ; molecular weight 171. Anal . Calcd for C 9 H 17 N0 2 : c » 63-13; H, 10.01; N, 8.18. Found: C, 63. Ml-; H, 10. U; N, 8. 31. Reaction of l-t-Butyl-2-Aziridinecarboxylate (5) With Hydrazine Hydrate ' in Ethanol — Methyl l-t-butyl-2-aziridinecarboxylate (5_, l.bl g, 0.01 mol) and hydrazine hydrate (1.0 g, 0.02 mol) were added together with enough ethanol (1 ml) to effect solution. The solution was refluxed for five 18 * This is a standard procedure for making carboxylic acid hydrazides.

PAGE 77

63 hours, cooled to room temperature, and the solvent was evaporated. Evaporative distillation of the residual oil gave 0.91 g (65%) of 3t-butylaminopropionic acid hydrazide (6): bp 100° (0.1 mm); ir (nujol) 3140 (NH) and 1655 cm" 1 (C = 0) ; nmr (D^) 5 2.25 (s, 9, t-butyl) , 2.54 (m, 2, CHg), and 2.99 (m, 2, CH_ 2 ) ; molecular weight 159. Anal . Calcd for CJ N 0: C, 52.80; H, 10. 76; N, 26.39. Found: C, 51.56; H, 10.50; N, 26. 17. l-t-Butyl-2-Aziridinecarboxyllc Acid Hydrazide (9) Methyl l-t-butyl-2-aziridinecarboxylate (5, 1.57 g, 10.0 ramol) and hydrazine hydrate (0.45 g, 9.0 mmol) were stirred at room temperature for 9.5 hours. The resulting oil was then triturated with cyclohexane. Residual cyclohexane was then removed by evaporation in vacuo to give a clear oil. Nmr observation of the oil indicated that 89% of the t-butyl containing species present was the aziridine hydrazide (9). Also present were some methanol and starting ester: nmr (DO; spectrum No 5) 5 1.26 (s, 9, t-butyl), 2.17 (m, 2, ring protons), and 2.64 (dd, 1H, ring proton) . l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (13 ) Methyl l-benzyl-2-aziridinecarboxylate (12, 15 g 0.078 mol) and hydrazine hydrate (3-85 g, 0.077 mol) were stirred together at room temperature for 40 minutes. The reaction mixture was then seeded with a small crystal of 15 . and the reaction mixture solidified to a cake. Attempted recrystallization from benzene caused some decomposition. The reaction mixture was dissolved in hot benzene, treated with de-

PAGE 78

6k colorizing charcoal, and cooled. After filtration 9.7 g (66%) of colorless crystals were recovered and identified as l-benzyl-2-aziridinecarboxylic acid hydrazide (l^): mp 92-96°dec; ir (nujol) 3200 (NH) , 1650 (C =0), 730, and 693 cm (phenyl); nmr (CDC1 ; spectrum No 6) 6 1.79 (m, 1, ring proton), 1.97 (m, 1, ring proton), 2.25 (dd, 1, ring proton), 3-5 (s, 2, 001^), 3-65 (broad, 3, NgH ) , and 7.3I (s, 5, C^) ; molecular weight 191. The l-benzyl-2-aziridinecarboxylic acid hydrazide (13) was characterized as the acetone hydrazone 15 . l-Phenyl-2-Aziridinecarboxylic Acid Hydrazide (1U ) Methyl l-phenyl-2-aziridinecarboxylate (12, 10.78 g, 0.06 raol) and hydrazine hydrate (3.0 g, 0.06 mol) were stirred together at room temperature for one hour. Benzene (25 ml) was added and removed by e^aj oration _in vacuo . Ether (25 ml) was added and a solid formed which was then washed with ether to give 5.8 g (5V/o) of the aziridine hydrazide (JUt): mp 67-75°dec; ir (nujol) 3220 (NH) , I670 (C = 0) , 760, and 693 cm (phenyl); nmr (CDC1 ; spectrum No 7) 5 2-32 (m, 2, ring protons), 2.78 (dd, 1, ring proton), 1+.05 (broad, 3, N 2 H ) , and 7.05 (m, 5, C^H ) ; molecular weight 177. The l-phenyl-2-aziridinecarboxylic acid hydrazide (Ik ) was characterized as the acetone hydrazone 16. l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide-Acetone Hydrazone (15 ) Methyl l-benzyl-2-aziridinecarboxylate (12, 1.83 g. 9.5 mmol) and hydrazine hydrate (0.1+78 g, 9.5 raraol) were stirred together and warmed

PAGE 79

65 on a steam bath for ten minutes. A white cake formed which was then dissolved in acetone (10 ml). After about ten minutes 2.2 g (70%) of colorless crystals of the hydrazone (15) precipitated. They were recrystallized from methanol: mp 143-144°; ir (nujol) 1780 (C = 0) , 1665, (C = N) , 730, and 695 cm" (phenyl); nmr (CDC1 ; spectrum No 8) 5 1.79 (s, 3, CH ), 1.95 (m, 2, ring protons), 2.04 (s, 3, CH ) , 2.35 (dd, 1, ring proton), 4.55 (q, 2, 00]^), and 7.31 (s, 5, CJy ; molecular weight 231. Anal. Calcd for C H N 0: c » 67-51; H, 7. 41; N, 18. 17Found: C, 67-59; H, 7. 41; N, 18.21. l-Phenyl-2-Aziridinecarboxylic Acid Hydrazide-Acetone Hydrazone (16) l-Phenyl-2-aziridinecarboxylic acid hydrazide (14» 0-2 g, 1.0 mmol) was dissolved in acetone (7 ml) at room temperature. In about five minutes 0.17 g (70%) of the hydrazone (16) precipitated. It was recrystallized from methanol: mp 161-174 dec; ir (nujol) 3113 (NH) , 1690, 1670, and 1640 cm (C = and C = N) ; nmr (CDC1 ; spectrum No 9) 5 1.85 (s, 3, CH ), 2.09 (s, 3, CH ) , 2. 31 (m, 2, ring proton), 2.89 (dd, 1, ring proton), and 7.1 (m, 5, C^H ) : molecular weight 217Anal. Calcd for C 12 H 15 N 3° : C » 66 '^' H ' 6,96; N ' l9 '^' Found: C, 66.49; H, 7.05; N, 19-39Reaction of l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) With Water Methyl l-t-butyl-2-aziridinecarboxylate (5, 1.57 g, 10.0 mmol) and hydrazine hydrate (0.48 g, 9.5 mmol) were stirred for nine hours at room temperature. The resulting oil, crude l-t-butyl-2-aziridine-

PAGE 80

66 carboxylic acid hydrazide (j)) , was then refluxed overnight in water (15 ml).. The resulting reddish brown solution was cooled to room temperature and concentrated. On standing overnight 0.2 g (15%) of 3-tbutylaminopropionic acid (11) precipitated and was identified by comparison of ir and nmr spectra and mixed melting point with an authentic sample. * 3-t-Butylaminopropionic Acid (11) t-Butylamine (3-65 g, 0.05 mol) was added to a solution of acrylic acid (3.60 g, 0.05 mol) in pyridine (10 ml). Evolution of heat and the instantaneous formation of a colorless solid were observed. The mixture was then refluxed for three hours. The solution was allowed to cool to room temperature, and the solvent was removed by rotary evaporation. The residue was washed with acetone to give 5.68 g (79%) of 3-t-butylaminopropionic acid (11) ; mp 229-230°; ir (nujol) 3300 (NH) , 1630 and 151+0 cm" 1 (C = 0) ; nmr (D^) 8 1.61+ (s, 9, t-butyl) , 2.81+ (m, 2, qy and 3.5U (m, 2, Ciy ; molecular weight 11*5. Anal. Calcd for CJ^ N 0: C, 52.80; H, 10. 76; N, 26-39. Found: C, 51.56; H, 10.50; N, 26. 17. Thermal Decomposition of l-t-Butyl-2-Aziridinecarboxylic Acid Hydrazide (9) Methyl l-t-Dutyl-2-aziridinecarboxylate (5, 311+ g, 0.02 mol) and hydrazine hydrate (1.0 g, 0.02 mol) were mixed and allowed to sit at room temperature for five days. A colorless solid precipitated which after recrystallizatiom from ethanol gave O.36 g (137.) of l,2-di-3-t* This gynthesj.3 was patterned after the synthesis of an analogous |3amino acid. 80

PAGE 81

67 butylaminopropionyl hydrazine (10) : mp 159-160 ; ir (nujol) 3075 (NH) , 1690 and 1685 cm" 1 (C =0); nmr (D 2 0) 6 1-34 (s, 9, t-butyl) , 2.67 (m, 2, CH ), and 3.I7 (m, 2, CH ) ; molecular weight 286. Anal . Calcd for C 1 ^ H 30 \° 2 : c > 58-71; H, 10.56; N. 19.56. Found: C, 58.81; H, 10.22; N, 19. 36. Fragmentation of l-t-Butyl-2-Aziridinecarboxvlic Acid Hydrazide (9) in the Presence of Azobenzene A solution of azobenzene (0.84 g, U.6 mmol) in methanol was added to a solution of l-t-butyl-2-aziridinecarboxylic acid hydrazide (_9, 1.5 g, 9.0 mmol) in methanol (25 ml) at room temperature. The resulting solution was refluxed overnight. Tic (benzene/alumina) showed disappearance of azobenzene and appearance of hydrazobenzene. When the solution was concentrated, 0.22 g (26%) of crystals precipitated and were identified as hydrazobenzene after washing with cyclohexane: mp 120-124 (Lit. 125126). 87 The filtrate was evaporated to a solid which after washing with ether yielded 0.1 g (8%) of 3-t-butylaminopropionic acid (1_1) . Thermal Decomposition of l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (13) in Water l-Benzyl-2-aziridinecarboxylic acid hydrazide (13, O.k g, 2.0 mmol) was dissolved in water and refluxed for three hours, then cooled to room temperature and extracted with ether. The water layer was evaporated to precipitate colorless crystals which were recrystallized from methanol to give 0.1 g (267.) of 3-benzylarainopropionic acid QJ) . This was iden-

PAGE 82

68 tified by comparison of ir spectra and mixed melting point with an authentic sample. ^-Benzylaminopropjonic Acid (17) 8 ° Acrylic acid (3.6 g, 0.05 mol) and benzylamine (5.3 g, 0.05 mol) were refluxed in pyridine for three hours, then cooled to room temperature. On standing, 3.8 g (k27o) of 3-benzylaminoprop ionic acid (1JJ precipitated. This was recrystallized from methanol: mp 182-186 ; (Lit. 182-183°) ; 88 ir (nujol) 1630, 1570 (C = 0) , 750, and 700 cm" 1 (phenyl); nmr (DgO) 5 2.87 (t, 2, CHg) , 3-55 (t, 2, CHg) , k.5k (s, 2, 0CH ) and 7. 80 (s, 5, C^) . Thermal Decomposition of l-Benzyl-2-Aziridinecarboxylic Acid Hydrazide (13) i" Methanol A solution of l-benzyl-2-aziridinecarboxylic acid hydrazide (13 . 1.0 g, 5.0 mrool) was refluxed overnight in methanol (25 ml). The solution was cooled to room temperature and evaporated to an oil which on distillation gave 0-37 g (37%) of methyl 3-benzylaminopropionate (18) : bp 90° (0.5 ram). An aliquot of the oil was dissolved in anhydrous ether (25 ml), and dry HC1 gas was bubbled through the solution to pre» cipitate the hydrochloride (19 ) of methyl 3-benzylaminopropionate. This was recrystallized from ethanol to give colorless needles: mp 159-160°. Identification was made by comparison of ir and nmr spectra and mixed melting points with an authentic sample.

PAGE 83

69 Methyl 3-Benzylaminopropionate (18) Benzylaraine (6.22 g, 0.058 mol) was added to a solution of methyl acrylate (5.0 g, 0.058 mol) in methanol (50 ml), and the solution was allowed to sit at room temperature overnight. Methanol was removed by evaporation to give 11.2 g (100%) of methyl 3-benzylaminopropionate (18) . Dry HC1 was bubbled through a solution of JL8 in anhydrous ether to precipitate the hydrochloride (19 ) of methyl 3-benzylaminopropionate. This was recrystallized from ethanol: mp 155-157° (Lit. 155-156°) ; 89 ir (nujol) 1738 (C = 0), 76I+ and 696 cm" 1 (phenyl); nmr (D 2 0) 5 3. 21 (t, 2, CHg), 3-68 (t, 2, CHg), 1+.07 (s, 3, CH 5 ), k.62 (s, 2, 0CHg) , and 7.83 (s, 5, C^H,.) ; molecular weight 206. Fragmentation of 1-Ben7.yl-2-Aziridinecarboxylic Acid Hvdrazide (IV ) in the Presence of Azobenzene — l-Benzyl-2-aziridinecarboxylic acid hydrazide (13 . 0.89 g, k.6 mmoi) was added to a solution of azobenzene (0.25 g, l.k mmol) in methanol (25 ml) and refluxed for six hours. Tic (benzene/alumina) showed the disappearance of azobenzene and the appearance of hydr azobenzene. The solution was evaporated to an oil. Thick layer chromatography (benzene/ alumina) gave 0.33 g °f a mixture of azobenzene and hydrazobenzene and 0.M) g (^57.) of methyl 3-benzylaminopropionate (18) . The mixture of azobenzene and hydrazobenzene was column chroma tographed (benzene/alumina) to give 0.085 g (9%) of hydrazobenzene which was recrystallized from methanol: mp 125-127° (Lit. 126-127°).

PAGE 84

70 3-Anlllnoproplonlc Acid Hydrazide (8) l-Phenyl-2-aziridinecarboxylic acid hydrazide (Ut, 0.90 g, k-7 mmol) was dissolved in a solution of hydrazine hydrate (10 ml) in ethanol (10 ml) and refluxed for one hour. The solvent was evaporated to give an oil. Benzene (10 ml) was added and evaporated to give 0.87 g (92%) of crystalline 3-anilinopropionic acid hydrazide (8). This was recrystallized from benzene: mp 89-90° (Lit. 95-96°) ; ir (nujol) 3225 (NH), 1638 (C = 0) , 7I4.I+ and 61+3 cm" 1 (phenyl); nmr (D^) 6 2.78 (t, 2, J = 7 Hz, CH 2 ), 3.72 (t, 2, J = 7 Hz, CH^) , f.k (m, 5, C,fl 5 ) ; molecular weight 179. 1,2-Diphenylaziridine (21) This was prepared according to the procedure of E. J. Corey and 90 M . C ha ykov s ky . l-t-Butyl-2-Aziridinecarbinol (22) ko This was prepared according to the procedure of C. L. Moyer. Ethyl Benzylaminoacetate This synthesis was patterned after a procedure by Speziale and 91 Jaworski. Ethyl chloroacetate (2k. k g, 0.2 raol) was added dropwise with stirring to an ice cooled solution of triethylaraine (20.2 g, 0.2 mol) and aniline (21. h g, 0.2 mol) in benzene (130 ml). The temperawas complete the reaction mixture was stirred at room temperature for one hour. Then potassium iodide (2.0 g) was added, and the reaction

PAGE 85

71 mixture was refluxed overnight. It was then allowed to cool to room temperature and washed with aqueous sodium carbonate and then water. The benzene was removed by evaporation, and the residual oil was distilled to give 25.8 g (67%) of ethyl benzylaminoacetate: bp 91-95 (0.2 mm) [Lit. 165° (16 mm)]; 92 ir (liquid film) 3250 (NH) , l^JkO (C = O), 7^0 and 700 cm" 1 (phenyl); nmr (CC1 ) 5 1.2 (t, 3, QH ) , I.76 (broad, 1, NH), 3-25 (s, 2, CH^) , 3-70 (s, 2, CH^) , l*.l (q, 2, CH^CH) , and 7.2 (s, f, CgH 5 ). • Benzylaminoacetic Acid Hydrazide (23) Ethyl benzylaminoacetate (6.0 g, 0.03 mol) was stirred neat with hydrazine hydrate (2.0 g, 0.014mol) . The heterogeneous mixture was warmed on a steam bath for three minutes, then stirred at ambient temperature fur one hour as the mixture become homogeneous. A seed was added and a colorless cake formed. The cake was recrystallized from isopropanol to give 3.62 g (65%) of benzylaminoacetic acid hydrazide (22): mp 80-82° (Lit 82-81*°) ; ° 5 ir (nujol) 321*5 (NH) , l6l)-5 (C =0), 745 and 700 cm" (phenyl); nmr (CDC1 = 3.5 (broad, 3, N H ) , 3.30 (s, 2, CH 2 ), 3-72 (s, 2, CHg), and 7.29 (s, 5, C^) J molecular weight 179. Anilinoacetic Acid Hydrazide (2k ) Hydrazine hydrate (lj..O g, 0.08 mol) was added to a solution of ethyl anilinoacetate (3.58 g, 0.02 mol). The mixture formed a solid cake within a few minutes. Ethanol (20 ml) was added, and the mixture was refluxed for two hours. Colorless plates precipitated on cooling. They were recrystallized from ethanol to give 2.95 g (89%) anilino

PAGE 86

72 acetic acid hydrazide (2Jt) : mp 125-126.5° (Lit. 126.5°) ; 9 ^ ir (nujol) 5280 (NH), 1650 (C =0), 745 and 685 cm" 1 (phenyl); nmr (D p 0) 6 4.09 (s, 2, CH ), and 7.25 (m, 5, C^) . 1.2-Diphenylaziridine (21) -Stability to Hydrazine Hydrate 1,2-Diphenylaziridine (21, 0.95 g, 5.0 mmol) and hydrazine hydrate (0.04 g, 7-0 mmol) were mixed together with enough methanol (4 ml) to effect solution. The solution was left at room temperature for four days. Solvent was removed by evaporation. An nmr spectrum of the residue indicated that no reaction had occurred. l-t-Butyl-2-Aziridinecarbinol (22) -Stability to Hydrazine Hydrate Hydrazine hydrate (0-71 g, 15.0 mmol) was added to l-t-butyi-2aziridinecarbinol (22, 0.96 g, 7.5 mmol) and enough methanol to effect solution. The solution was left at room temperature for four days. Solvent was removed by evaporation. An nmr spectrum of the residue indicated that no reaction had occurred. Benzylaminoacetic Acid Hydrazide (25) -Stability to Methanol Benzylaminoacetic acid hydrazide (2^, 0.57 g, 3.2 mmol) was refluxed in methanol (25 ml) for 24 hours. Tic (chloroform-methanol/ alumina) indicated that no reaction had taken place. Solvent was removed by evaporation. The residual oil was taken up in 2-propanol, and the resulting solution, when seeded, yielded 0.54 g (957.) of 2J£:

PAGE 87

73 Anilinoacetic Acid Hydrazide (24)-S tability to Methanol Anilinoacetic acid hydrazide (2ifc, 0.54 g, 3.27 ramol) was refluxed in methanol (25 ml) for 2k hours. Tic (chloroform/alumina) indicated that no reaction had occurred. Solvent was removed by evaporation to give 0.59 g, (100%) of £&: mp 124-126.5°. Ethyl g, g-Tetramethyleneglycidate In a flame dried apparatus ethyl chloroacetate (12.2 g, 0.1 mol) , cyclopentanone (8.4 g, 0.1 mol), and dry diglyme (50 ml) were stirred at ice-salt temperatures. Potassium t-butoxide (11.6 g, 0.1 mol) was added over a period of 1.25 hours and the resultant mixture was stirred at that temperature for two hours, then at room temperature for five hours. Hydrochloric acid (6N) was added until the solution was slightly acidic (yellow to pH paper) and solids were removed by centrifugation and filtration and washed with ether. Solvent was removed from the filtrate by evaporation to give a dark oil which on distillation gave 7. 84 g (467.) of ethyl P, p-tetramethyleneglycidate: bp 80-8'+° (2-3 mm) [Lit. 90-95° (3-4 mm) ] ; ir (liquid film) 3000 (CH) and 1750 cm" 1 (C = 0); nmr (CC1.) 6 1.29 (t, 3, CH ) , I.78 [broad m, (CHg),], 3.33 (s, 1, CH) , and 1<..18 (q, 2, CH CH ) . The nmr spectrum also contained signals indicative of some t-butyl |3, (3-tetramethyleneglycidate as a major impurity. * This procedure was patterned after a similar synthesis by U. V. Moyer. 95

PAGE 88

74 3,3-Tetramethylene-4-Hydroxy-5-Pvrazolidone Hydrazine hydrate (0.29 g, 5.9 mraol) was added to ethyl p, £5tetramethyleneglycidate (1.0 g, 5.9 mmol) and the resultant mixture was warmed on a steam bath for 20 minutes. On cooling to room temperature 0.26 g (287 ) of 3>3"tetramethylene -4-hydroxy-5-pyrazolidone pre184-185°) ; 28a ir (nujol) 1685 cm" 1 (C = 0) ; nmr (D^) 8 2.13 [broad m,8, (CH ) ,], and 4.76 (s, 1, CH) ; molecular weight 155. Sodium and Lithium l-t-Butyl-2-Aziridinecarboxyl a te (55 and k9 ) Sodium and lithium l-t-butyl-2-aziridinecarboxylate (5Jj and l±9) were prepared according to procedures patterned after those of C. L. Moyer . Methyl l-t-buty]-2-aziridinecarbcxylate (5, 10 g 0.064 raol) and sodium hydroxide (2.04 g, 0.051 mol) were stirred in water (25 ml) at room temperature overnight. The resulting clear solution was then washed twice with chloroform (20 ml) and evaporated to a fine powder. The powder was dried under vacuum to give 8.14 g (S6%) of the sodium salt (55) which was identified by spectral properties. Lithium l-t-butyl-2-aziridinecarboyxlate (49) was prepared in an analogous manner (14.0 g, 94%) from lithium hydroxide monohydrate (4.2 g, 0.1 mol) and l-t-butyl-2-aziridinecarboxylate (15-7 g, 0.1 mol)

PAGE 89

75 Sodium Cis-l-t-Butyl-^-Methyl-2-Aziridinecarboxylate (67) Methyl c_is-l-t-butyl-3-methyl-2-aziridinecarboxylate (65, 7.35 g, 0.043 m °l) wa s stirred overnight at room temperature with sodium hydroxide (1.68 g, 0.042 mol) in water (50 ml). The resulting solution was washed with chloroform and evaporated to 7«44 g (99%) of the sodium salt (67) ; ir (nujol) loOO cm" (CO ") ; nmr (DO; spectrum No 3) 5 1.30 (s, 9, t-butyl), l.kk (d, 3, CH ) 2.48 (m, 1, CJ1) , and 2.74 (d, 1, CJl 2^ Sodium Trans-l-t-Butyl-3-Methyl-2-Aziridinecarboxylate (68) Methyl trans -l-t-butyl-3-methyl-2-aziridinecarboxy late {66 , 1.20 g, 7.0 mmol) and sodium hydroxide (0.28 g. 7.0 mmol) were stirred together in water (15 ml) at room temperature overnight. The resulting solution was evaporated to 1.19 g (96%) of the sodium salt (68) : ir (nujol) 1615 and 1590 cm" (CO ") ; nmi (DO; spectrum No 4) 8 1.45 (s, 9, t-butyl), 1.58 (d, 3, J = 6 Hz, CH ), and 2.6l (m, 2, ring protons). Triphenylmethyl 1t-Butyl-2-Aziridinecarboxylate (91 ) Sodium l-t-butyl-2-aziridinecarboxylate (J5_3_, 8.0 g, 0.048 mol) was added to benzene (200 ml) , and then some benzene (25 ml) was removed by distillation to remove water. Solid triphenylmethyl bromide (8.0 g, 0.0248 mol) was added along with enough benzene to make the total volume about 200 ml. The resulting slurry was stirred rapidly at a reflux for 14 hours, then cooled to room temperature. Solids were

PAGE 90

76 removed by filtration through filter cell and washed with benzene. The filtrate was evaporated to an oil which was treated with hexanes (15 ml) and placed in a refrigerator to precipitate 5.2 g (52%) of triphenylmethyl l-t-butyl-2-aziridinecarboxylate (91) . Repeated recrystallizations from hexanes gave a pure product: mp 117-118 ; ir (nujol) 1730 (C m 0), 790 and 710 cm" (phenyl); nmr (CC1, ; spectrum No 10) 6 0.95 (s, 9, t-butyl), 1.59 (dd, 1, ring proton), 1.92 (dd, 1, ring proton), 2.12 (dd, 1, ring proton), and 7.20 (m, 15, triphenylmethyl) ; molecular weight 385. Anal . Calcd for C^H m^. C, 81.01; H, 7.06; N, 3.63. Found: C, 81.00; H, 7.I6; N, 3.62. Pyrolysis of Triphenylmethyl l-t-Butyl-2-Aziridinecarboxylate (91) in Benzene Benzene (10 ml) was added to triphenylmethyl l-t-butyl-2-aziridinecarboxylate (91, 0.^0 g, 1.0 mmol) in a thick-walled glass tube (25 cm x 1.5 cm). The tube was flushed with dry nitrogen, cooled in a dry iceacetone slush, sealed, and placed in an oven (175-180 ) for Ik hours. When the tube was again cooled in a dry ice-acetone slush and opened, considerable pressure was released. After concentrating the contents of the tube to an oil, the reaction mixture was column chroma tographed (10% alumina, 1.0 cm x 30 cm, 30 g) using cyclohexane as the eluent. Two components were isolated and characterized. The first component to come off the column was 0.16 g (1+5%) of l-t-butyl-2-triphenylmethylaziridine (95) . This was recrystallized from ethanol: mp 1114.-115°; ir (nujol) 1325 and U30 cm (phenyl); nmr (CDC1 ; spectrum No 11) 5 0.83 (s, 9, t-butyl), 1.02 (dd, 1, ring

PAGE 91

77 proton), 1.50 (dd, 1, ring proton), 2.90 (dd, 1, ring proton), and 7.2 (broad s, 15, triphenylmethyl) ; molecular weight Jlj-l. Anal. Calcd for C^H Jj C, 87-93; H, 7.97; N, 1^.10. Found: C, 87-98; H, 8.09; N, 2^.00. The second component to come off the column was 0.08 g (257,) of a colorless solid characterized as N-t-butyl-triphenylmethylraethylamine (96). This was recrystallized from ethanol: mp 108-109°; ir (KBr) 3040 (NH), 764 and 699 cm" 1 (phenyl); nmr (CC1 ) 5 O.36 (broad, 1, NH), 1.04 (s, 9, t-butyl), 3-65 (s, 2, CHg) , and 7. 19 (s, 15, triphenylmethyl) ; molecular weight 330. Anal. Calcd for C^H N: C, 87-49; H, 8.26; N, 4.25. Found: C, 87-62; H, 8. 31; N, 1^.30. Thermal Decomposition of Triphenylmethyl 1-t-Butvl2-A^iriuinecarbuxvlaLL: (91) in Cumene Cumene was purified according to the procedure of U. V. Moyer. Triphenylmethyl 1-t-butyi -2-aziridinecarboxylate (91, 0.45 g, 1.17 mmol) was dissolved in cumene (8 ml) in a thick walled glass tube fitted with a ground glass joint. The solution was degassed by alternately freezing and thawing the solution under vacuum (0.05 mm). The hours. The tube was then cooled and opened, and the contents examined. Gas chromatography (SE-30, 5 ft. x 0.12 in., 238°) showed no trace of dicumyl. By examination of standard solutions it was estimated that 0.2% of the theoretical amount of dicumyl could be detected. The solution was then evaporated to a crude oil. Nmr observation showed the reaction mixture to be essentially identical to the reaction

PAGE 92

78 in benzene. It was estimated that l-t-butyl-2-triphenylmethylaziridine (95) comprises 57% of the reaction products and N-t-butyl-triphenylmethylmethylamine (96 ) 327.. By column chromatography 0.23 g (57%) of the aziridine (95) and 0.05 g (12%) of the amine were recovered. Pyrolysis of Trlphenylmethyl l-t-Butyl-2-Aziridinecarboxy late (91) in Benzene in the Presence of t-Butanol Trlphenylmethyl l-t-butyl-2-aziridinecarboxylate (91, 0.^-5 g, 1.17 mmol) , t-butanol (0.08 g, 1.17 mmol) , and benzene (8 ml) were placed in a glass tube. Dry nitrogen was bubbled through the solution and the tube was sealed after cooling in a dry ice-acetone slush. The tube was then placed in an oven (160 + 10 ) for ten hours, cooled, and opened. The contents of the tube smelled faintly of formaldehyde. The benzene solution was washed with water. The water wash gave a 97 positive color test with Fuchsin-aldehyde reagent. When treated with aqueous dimedone reagent a colorless solid precipitated which was recrystallized from ethanol-water to give colorless needles: mp 188-189 (Lit. formaldehyde-dimedone derivative: 189 ). The benzene layer was dried (MgSO, ) and evaporated to O.kk g of an oil. The nmr spectrum indicated that the oil consisted of 1-tbutyl-2-triphenylmethylaziridine (95, 11%) and N-t-butyl-triphenylmethylmethylaraine (96, 88%). The oil was recrystallized from ethanol to give the 0.172 g (50%) of the amine (96): mp 105-107°. Thermal Stability of l-t-Butyl-2-Triphenylmethylaziridine (95) The aziridine (95, 0.05 g) was dissolved in benzene and placed in a thick-walled glass tube. Nitrogen was bubbled through the solu-

PAGE 93

79 tion, and the tube was cooled in a dry ice-acetone slush and sealed. It was placed in an oven (180 + 10 ) for 11*. hours, cooled, and opened. Tic (eye lohexane /alumina) showed only one spot due to the starting aziridine. The benzene was evaporated leaving a clean oil, and nmr observation of the oil showed only clean starting aziridine. The oil was recrystallized from ethanol to give 0.38 g (76%) of the aziridine (95) . Pyrolysis of Triphenylmethyl l-t-Butyl-2-Aziridinecarboxylate (91) in Methanol Nitrogen was bubbled through a solution of triphenylmethyl l-t-butyl-2-aziridinecarboxylate (92 , 0.50 g, 1.3 mmol) in methanol (5 ml) in a glass tube. The tube was sealed (-70 ) and placed in an oven (120 + 10 ) for Ik hours. The solution turned brown. On cooling 0.27 g (75%) of methyl triphenylmethyl ether precipitated. It was identified by comparison to an authentic sample. The filtrate showed no moving spots on tic (benzene/alumina) . An nmr spectrum of the residual oil left after evaporation of the solvent showed no recognizable signals. Methyl Triphenylmethyl Ether This was prepared by a procedure patterned after that of Norris 99 and Young. Triphenylmethyl bromide (3.73 g> 0.01 mol) and sodium methoxide (0.5U g, 0.01 mol) were refluxed in methanol for ten hours. On cooling 2.26 g (82%) of methyl triphenylmethyl ether precipitated. This was recrystallized from methanol: mp 80-80.5° (Lit. 82.6-82.9°).

PAGE 94

80 Reaction of Lithium l-t-Butyl-2-Aziridinecarboxylate (1+9) with Thionyl Chloride A sodium hydride suspension (0.96 g, 20.0 mmol) , washed three times with cyclohexane, was added to tetrahydrofuran (25 ml) under nitrogen to form a slurry. Lithium l-t-butyl-2-aziridinecarboxylate (1+9 , 1.0 g, 6.7 mmol) was added to the slurry followed by dropwise addition of thionyl chloride (1.19 g, 10. mmol). The resulting mixture was stirred at room temperature for 1.25 hours. Solvent was removed by evaporation, and cyclohexane (35 ml) was added followed by careful addition of water to destroy the sodium hydride present. The organic layer was separated and washed with water, dried (MgSO, ) , and, after evaporation of the solvent, distilled to give 0.25 g (237.) of l-t-butyl-3-chloro-2-azetidinone (50) ; bp 70 (0.2 mm); ir (liquid film) I76O (C =0), 811+, 71+5, and 695 cm" 1 (C-Cl); nmr (CC1 ; spectrum No 12) 6 1.31 (s, 9, t-butyl), 3-18 (dd, 1, CH) , 3.78 (dd, 1, CH) , and 4.57 (dd, 1, CH); molecular weight l6l, 163. Anal . Calcd for C 17 H 12 N0C1: c > 52.01; H, 7.1+3; N, 8.67. Found: C, 52.27; H, 7.65; N, 8.1+6. Slightly improved yields could be obtained by removing excess sodium hydride and salts by filtration followed by distillation of the residual oil: 33%.

PAGE 95

81 Reaction of Sodium 1t-Butyl-2-Aziridinecarboxylate (55) with Oxalyl Chloride * — Solid sodium l-t-butyl-2-aziridinecarboxylate (5_3_) , 1.05 g, 6.3 mraol) was added to a solution of oxalyl chloride (0.95 g, 7«5 mmol) in benzene (10 ml) at room temperature. Both heat and gas were evolved. The resulting slurry was refluxed for 15 minutes. Benzene (20 ml) was added, and the slurry was washed with aqueous sodium carbonate, water, and dried (MgSO,). Distillation of the residual oil left after evaporation of the solvent gave 0.266 g (26%) of l-t-butyl-3-chloro-2azetidinone (50). This was identified by spectral comparison to an authentic sample: bp 90 (0-7 m™) • Reaction of Sodium l-t-Butyl-2-Aziridinecarboxylate (55) with Oxalyl Chloride in the Presence of Triethylamine The sodium salt (5^> 1.05 g, 6.3 mmol) was slowly added to a mixture of oxalyl chloride (0.95 g, 7-5 mmol) and triethylamine (O.76 g, 7-5 mmol) in benzene (50 ml). The dark brown slurry was stirred at room temperature for one hour, washed with 5% HC1, sodium carbonate, and water, dried (MgSO,), and evaporated to 0.30 g(297.) of l-t-butyl-3-chloro-2azetidinone (50) . This was identified by comparison to an authentic sample. Reaction of Sodium Cis-l-t-Butvl-5-Methvl-2-Aziridinecarboxylate 167) with Oxalvl Chloride The sodium salt (6j, 3A g, 0.019 mol) was added slowly to a * This reaction was patterned after a general synthesis of acid chlorides.

PAGE 96

82 solution of oxalyl chloride (3-0 g, 0.0238 mol) in benzene (20 ml). The resulting slurry was stirred at ambient temperature for one hour, and then a few chips of ice were added. Benzene (20 ml) was added, and the reaction mixture was washed with sodium carbonate and water, dried (MgSO, ) , and evaporated to 3.2 g (98%) of a clean oil which was distilled to give 2.6 g (797.) of cis-1t-butyl3-chloro-l4.-nethyl-2-azetidinone (69): bp 65° (0.1 mm); ir (liquid film) 2930 (CH) , 1750 cm" 1 (C 0); nrar (CC1, ; spectrum No 15) 6 1-35 (s, 9, t-butyl) , 1.40 (d, 3, J = 6.k Hz, CH ), 4.01 (m, 1, CHN), and k-10 (d, 1, J = 5.1 Hz, CKCO) ; molecular weight 175, 177. The oil was redistilled for an analytical sample, but even when stored under a vacuum it was unstable at room temperature. Thus it is not surprising that the analytical sample did not check. Anal . Calcd for C.H..N0C1: C, 54.66; H, 8.03; N, 7.98. o 14Found: C, 53.83; H, 7.93; H, 8.02. Reaction of Sodium Trans-l-t-Butyl-3-Methyl-2-Aziridinecarboxylate (oS) with Oxalyl Chloride — A mixture composed of sodium trans 1t-butyl3-methyl-2-aziridinecarboxylate (68, 1.3 g, 3.0 ramol) and an inert salt was added slowly to a solution of oxalyl chloride (1.09 g, 8.7 mmol) in benzene (25 ml). The resulting slurry was stirred at room temperature for one hour, washed with 57. HC1, aqueous sodium carbonate, and water, and dried (MgSO,). The solution was evaporated to 0.33 g (637.) of trans -1-tbutyl-3-chloro-l+-methyl-2-azetidinone (JO). The oil was distilled for an analytical sample: bp 65° (0.1 mm); ir (liquid film) 2900 (CH) and 1751 cm" 1 (C = 0) ; nmr (CC1 ; spectrum No 18) 6 1.34 (s, 9, t-butyl),

PAGE 97

83 1.45 (d, 3, J = 6.1 Hz, CH ), 3.68 (m, 1, CHN) , and 4.09 (d, 1, J = 1.7 Hz, CHCO) ; molecular weight 175, I77. Anal . Calcd for C H N0C1: C, 54.66; H, 8.03; N, 7.98. Found: C, 54-79; H, 7. 91; N, 7.87. R ing Expansion of Sodium l-t-Butyl-2-Aziridinecarboxylate (53) with Nosyl Chloride in Acetonitrile — The sodium salt (5J, 0.77 g, 4-7 mmol) and nosyl chloride (1.02 g, 4.7 mmol) were stirred together in benzene (50 ml) for four hours at room temperature. The slurry was washed with water, dried (MgSO.), and evaporated to an oil which consisted of a mixture of nosyl chloride and l-t-butyl-2-aziridinecarboxylic acid anhydride (75a ; spectrum No 20). The oil was taken up in a solution of tetraethyl ammonium chloride (2.68 g, 16.0 mmol) in acetonitrile and left at room temperature overnight. The resulting orange solution was evaporated to an oil, taken up in petroleum ether (bp 37-46°), washed with water, dried (MgSO ) , and evaporated to a pale yellow oil (0.202 g) which was shown by nmr spectroscopy to consist of 1.3 g (17%) of l-t-butyl-3-chloro-2-azetidinone (50) together with some extraneous material. Ring Expansion of Sodium Cis-l-t-Butyl: ?-Methvl-2-Aziridine carboxylate (67) ^ith Nosyl Chloride In Acetonitrile The sodium salt (6J, 0.37 g> 2.0 mmol) and nosyl chloride (0*44 g, 2.0 mmol) were stirred together in benzene (50 ml) for four hours at room temperature. The slurry was washed with water, dried (MgSO,), and evaporated to an oil. The oil was dissolved in a solution of tetraethyl ammonium chloride (0-33 g, 2.0 mmol) and left at room temperature

PAGE 98

8k overnight. Acetonitrile was removed by evaporation and the residual oil was taken up in petroleum ether (bp 37~46 ), washed with water, dried (MgSO ) , and evaporated to 0.27U g (75%) of an oil identified as cis-l-t-butyl-3-chloro-l+-methyl-2-azetidinone (69) • Distillation (65°, 0.1 mm) gave 0.17 g (50%) of the pure product. Reaction of Sodium Cis-l-t-Butyl-3-Hathyl-2-Aziridinecarboxylate (67) with Nosyl Chloride — The sodium salt (6j, 0.5 g, 2.9 mmol) and nosyl chloride (0.64 g, 2.9 mmol) were stirred at room temperature in benzene (50 ml) for 1+.5 hours. The resulting slurry was washed with aqueous sodium carbonate and water, dried (MgSO ) , and evaporated to an oil consisting of a mixture of cis -l-t-butyl-$-methyl-2-aziridinecarboxylic anhydride ( 73b) and nosyl chloride. Nosyl chloride (0.13 g) was removed by several crystallizations from petroleum ether. The anhydride (73b) was obtained free of nosyl species by evaporation of the solvent from the mother liquor to give 0.214g (56%) as an oil. Cis-l-t-Butyl-3-Methyl-2-Aziridinecarboxylic Anhydride (75) Sodium cis -l-t-butyl-3-methyl-2-aziridinecarboxylate (67 . 1.0 g, 5.8 mmol) and nosyl chloride (0.62 g, 2.8 mmol) were stirred together in benzene at room temperature for 14-. 5 hours. The resulting slurry was washed with water, aqueous sodium carbonate, and again with water, dried (MgSO ) , and evaporated to 0.633 g (76%) of an oil identified as cis -l-t-butyl-3-methyl-2-aziridinecarboxylic anhydride (13b). The oil was taken up in petroleum ether (bp 37-W5 ) and filtered to remove a fine insoluble suspension. Evaporation of the filtrate gave 0.57!+ g

PAGE 99

85 (697.) of the anhydride (75b ) as an oily solid: ir (liquid film) 2920 (CH), 1820, 1800, and I760 cm" (C = 0) \ nmr (CC1 • spectrum No 21) 5 1.0 (s, 9, t-butyl), 1.26 (broad d, 3, C H ) , and 2.15 (ra, 2, ring protons) . Reaction of Cis-l-t-Butyl-5-Ne thyl-2-Aziridinecarboxylic Anhydride (75 ) with Sodium Methoxide in Methanol in the Presence of Nosy! Chlorid~ Sodium ,cis-l-t-butyl-3-methyl-2-aziridinecarboxylate (§J_, 0.34 g, 2.0 mmol) and nosyl chloride (O.kk g, 2.0 mmol) were stirred 3t room temperature in benzene, washed with water, dried (MgSO ) , and evaporated to an oil composed of the anhydride (75 ) and nosyl chloride. The oil was dissolved in a solution of sodium methoxide (0.10 g, 1.8 mmol) in methanol and left at room temperature overnight. The resulting solution was poured into benzene and washed with water. The benzene layer was dried (MgSO ) and evaporated to an oily solid. The residue was taken up in chloroform and the solids were removed by filtration. The chloroform solution was evaporated to 0.118 g (557.) of an oil identified as methyl c is 1t-butyl5-methyl-2-aziridinecarboxy la te (65) by spectroscopy. The water layer was evaporated to a solid which was identified as a mixture of sodium nosylate and sodium c is 1t-butyl5-me thy 1-2-aziridinecarboxylate (6_7J by nmr spectroscopy. Reaction of Sodium Trans-l-t-Butyl-5-Methyl-2-Aziridinecarboxylate (68) with Nosyl Chloride Sodium trans 1t-butyl5-me thyl-2-aziridinecarboxy late (68 , 0.3 g, 1.7 mmol) and nosyl chloride (0.388 g, 1.7 mmol) were stirred in benzene

PAGE 100

at room temperature for four hours. The resulting slurry was washed with aqueous sodium carbonate and water, dried (MgSO, ) , and evaporated to an oil (0.38 g) consisting of a mixture of trans l-t-butyl-3-methyl2-aziridinecarboxylic anhydride (73c )and unreacted nosyl chloride: nmr (CC1 ; spectrum No 20) 5 1.17 (s, 9, t-butyl), 1.1+2 (m, 3, CH ) , 2.30 (d, l s C£L), and 2.60 (m, 1, CJ). Nmr of the Anhydrides in Sulfur Dioxide o The anhydrides were dissolved in liquid sulfur dioxide at -10 and transferred in a laboratory atmosphere to nmr sample tubes which were sealed. Samples of the anhydrides with nosyl or tosyl chloride present were prepared by treating the appropriate sodium salts with equimolar amounts of the arylsulfonyl chlorides and dissolving the residual oil left after the usual workup in sulfur dioxide as above. The same spectra could be obtained by adding the arylsulfonyl chlorides to solutions of the anhydride in sulfur dioxide, but this was found to be less convenient. The chemical shifts for the ionized and unionized anhydrides are reported with reference to external tetramethylsilane in carbon tetrachloride and are tabulated in Tables IV and V. The solution of the cis anhydride in the presence of nosyl chloride or tosyl chloride (after ionization had occuired) was quenched by pouring the sulfur dioxide solution into a solution of tetraethyl ammonium chloride in acetronitrile. After the usual workup c is -1t-butyl3chloro-l4.-methyl-2-azetidinone was recovered in yields of 13% and lk% respectively.

PAGE 101

87 Nmr Spectra of 3-Chloro-2-Azetidinones in Antimony Pentafluoride-Sulfur Dioxide Sulfur dioxide (2 ml) at -10 was saturated with antimony pentafluoride and cooled to -70 . Approximately 300 mg of l-t-butyl-3chloro-2-azetidinone (50) was dissolved in the resultant solution, and an aliquot was sealed in an nmr sample tube. The spectrum of the solution (spectrum No Ik) was compared to a spectrum of the same azetidinone in sulfur dioxide (spectrum No 13) , and both are reported in Table VI. The antimony pentaf luoride-sulfur dioxide solution was poured into a solution of sodium methoxide in methanol (-70 ). This solution was then warmed to room temperature, poured into water, and extracted with benzene. The benzene layer was dried (MgSO, ) , and evaporated to a colorless oil identified as extremely clean l-t-butyl-3»chloro-2azetidincne (50) . In a similar fashion cis -l-t-butyl-3-chloro-l|-methyl-2-azetidinone (69) was treated with antimony pentaf luoride in sulfur dioxide. The nmr spectra, are recorded as above, and workup of the solution with sodium methoxide in methanol yielded only extremely clean cis -l-tbutyl-3-chloro-l4.-methyl-2-azetidinone (69) . Reduction of l-t-Butyl-3-Chloro-2-Azetidinone (50) with Zinc Zinc dust (2.5 g, 30 mmol) , activated by stirring two minutes in concentrated hydrochloric acid, washing If times with distilled water and I4. times with acetone (reagent grade), and drying .in vacuo for 15 minutes, was added to a solution of l-t-butyl-3-chloro-2-azetidinone (50, O.W g, 2.U.9 mmol) in ethanol. The heterogeneous mixture was then refluxed

PAGE 102

for ten days, cooled, filtered, and evaporated to an oil. The oil was distilled to give 0.13 g (41%) of l-t-butyl-2-azetidinone (51): bp 90-100° (25 mm) . l-t-Butyl-2-Azetidlnone (51) This was prepared by a procedure similar to that of Blicke and 39 Gould. " Triethylaraine (3-55 g, 35.0 mmol) was added in dry tetrahydrofuran (10 ml). A solution of thionyl chloride (1.4 g, 12.0 mmol) in tetrahydrofuran (10 ml) was slowly added to the stirred slurry. The resulting yellow mixture was stirred at room temperature for 14 hours, than filtered through filter cell, and the filtrate was evaporated to a dark brown sludge. The sludge was washed through 5% alumina with chloroform, and the eluent was evaporated to 0.085 g (7%) of a yellow oil identical to the l-t-butyl-2-azetidinone prepared by reduction of l-t-butyl-3chloro-2-azetidinone (50) : ir (liquid film) 2900 (CH) and 1740 cm" (C = 0) ; nmr (CC1 ; spectrum No 19) 5 1.28 (s, 9, t-butyl) , 2.68 (m, 2, CYU), and 3.12 (m, 2, CH ) ; molecular weight 127Anal . Calcd for C H NO: C, 66.11; H, 10-30; N, 11.01. Found: C, 66.02; H, 10.46; N, 10.92. Reaction of l-t-Butyl-3-Chloro-2-Azetidinone (50) with Sodium Hydroxide l-t-Butyl-3-chloro-2-azetidinone (50, 0.20 g, 1.2 mmol) was stirred with a solution of sodium hydroxide (0.06 g, 1.5 mmol) in water (5 ml) for two hours. The mixture was then refluxed for three hours. The

PAGE 103

89 resulting solution was cooled, and solvent was removed by evaporation to give 0.214-5 g (9k%) of a pale yellow powder in which the sole organic species present was identified as sodium l-t-butyl-2-aziridinecarboxylate (5JS) by comparison of the ir and nmr spectra with spectra of an authentic sample. Reaction of l-t-Butyl-^-Chloro-2-Azetidinone (50) with Sodium Methoxide — In a dry box l-t-butyl-3-chloro-2-azetidinone (50, 0.31 g, 1.8 mmol) was added to a solution of sodium methoxide (0.l6 g, 3.0 mmol) in methanol (2.5 ml) and left at room temperature for two days. The reaction mixture was poured into benzene (15 ml), washed with water, dried (MgSO ) , and evaporated to O.llf g (lj-8%) of an oil identified as methyl l-t-butyl-2-aziridinecarboxylate (5) by comparison of ir and nmr spectra with the spectra of an authentic sample. Reaction of Cis-l-t-Butyl-3-Chloro-l|-Methyl-2-Azetidinone (69) — w ith Sodium Hydroxide — The azetidinone (6_9, 0.30 g, 1.7 mmol) was dissolved in dioxane (1 ml), and the resulting solution was added to a solution of sodium hydroxide (0.16 g, l+O.O mmol) in water (2 ml). More water was added until the mixture became clear, and the solution was left at room temperature for 30 days. It was then washed with ether and evaporated to 0.38 g (83%) of a white powder identified as sodium cis -l-t-butyl-3methyl-2-aziridinecarboxylate (67) by comparison of the ir and nmr spectra with the spectra of a known sample.

PAGE 104

90 Reaction of Trans-l-t-Butyl->Chloro-l+-Methyl-2-Azetidinone (70) with Sodium Hydroxide — The azetidinone (JO, 0-30 g, 1.7 mmol) was dissolved in dioxane (1 ml), and the resulting solution was added to a solution of sodium hydroxide (0.18 g, 1*5.0 mrool) in water (2 ml). Water was added until the mixture became clear, and the resulting solution was left at room temperature for 21 days. It was washed with chloroform and evaporated to a white solid. Nmr observation showed that about 30% of the solid consisted of sodium trans l-t-butyl-3-methyl-2-aziridinecarboxylate (68). The other components of the mixture were not characterized.

PAGE 105

SPECTRA

PAGE 106

No , SOLVENT CCL 4 o. 0.95 (b) CH 3 ^__X 0C h 3 Cd (c) K / %/ N H (c) i t-Bu la) b. 1.17 c 205 d. 3.6 5 lo 2

PAGE 107

M ....... .y>. S3 >J to la »c H — : ; I ; ; , ta 5j5 — fWTTT / 1|_ zfZw _^_ ij £0 ' ts~ U 1A ' lid 1 • , »w«(» l ~7j y -4 10 IJ _/Aaa^_ _aAa/V^_ to us *a — —i3 — B«nr

PAGE 108

No 4 (c) (b) CH 3 >wf I tBu a ! (c) (a) SOLVENT a. I. 4 5 D 2 1. 58 2. 6 1 (c) H NO 5 A; Id) h^\/ h (b) I t-Bu (a) SOLVENT D 2 a. I. 2 6 b. 2. 6 4 or 217 c. 2-6 4 or 2.17 d. 2. 6 4 or 2. 17 No 6 (o) H A (b) H^V^ NHNH, (©) H (o) (f) SOLVENT CDCI 3

PAGE 109

=2F ia to nr ' ttstn 95 1.0 10 J^J V -^ VA j)\ A ^mJUa_

PAGE 110

No 7 (b) (c) 6 u) SOLVENT CDCI 3

PAGE 111

M U>_ 97 >j t-° i , , , : r ^JL-__xJ t~^ ^ ' , ' o : , 5 _A t j-jW-L I i ' . i , I , — r— ri .is ' ra — mtrr, — nr to

PAGE 112

No 10 « H : y,., (c) H 7 t-Bu (o) SOLVENT CDCI 3 a. 0. 9 5 I. 59, or I. 92, or 2. 12 I. 59, or I. 92, or 2.12 I. 5 9, or I. 92, or 2.12 7. 26 b. c. No II (t) H ^ /C0 3 U) (c) hA^H W) t-Bu (a) SOLVE

PAGE 113

99 10 J \ 11 4 J 'i iii if -M V,* Mna — wiTT — 2F ~> 12

PAGE 114

No 13 (d) h n f (c) H-J N lb) H tBu (a) SOLVENT

PAGE 115

101 " SSiZU _I* t» 10 13 -M*. VU \*L. ~a — ffim — *s~ T3 pfsm li* L_ 15 -tn — wsrrn — or

PAGE 116

No 16 (d) H^l f (b) CH 3> J_ N (c) H' \-Bu (a) SOLVENT S0 2 o. 0. 76 b. 0. 80 c. 3. 5 6 d. 4. 2 2 No 17

PAGE 117

zSz «i n . v i» i ',.•. . . r , ^c 103 16 r-4

PAGE 118

No 19 <» C>r-f Bu (a) SOLVENT CCI 4 a. 1.2 8 b. 2 6 8 c. 3. ! 2 No 20 (c) H (c) t-Bu (a) *-Bu (a) SOLVENT CCI 4 o. I. b. I. 8 8 or 2.25 c. I. 8 8 or 225 d. !. 8 8 or 2.25 No 21 (b) Ci (c) H > V^* > V < H w t-Bu (a) t-Bu CH 3 (b) (c) (o) SOLVENT CCI 4 o. I. b. I. 26 c. 2. I 5 d. 2. I 5

PAGE 119

10 WM ITI 4J TO 105 19 >LA_ Li T3 TWfTIT £5 — — "TS~ -r1 i ' =£ AU. j^V-'V-' 20 I _... ' i . ^ w 21 -is — »«m — is ' TT" ^~A' 1

PAGE 120

No 22 SOLVENT SO,

PAGE 121

107 jg vo xiz — i — ~zr 22 -JU \~ .a. .. — *.^*~„ j 4 r, XT 23 K Hi 4^__ 1_^„, M. ' i . i,,:^ 1 , i ' , -f 2k ^JL Wk_ x — t jl.' . , l.1, i _.,.,' j, =r±=a I 1

PAGE 122

BIBLIOGRAPHY 1. E. S. Gould, "Mechanism and Structure in Organic Chemistry," Holt, Rinehart, and Winston, New York, N. Y. , 1959; C. D. Ritchie and W. F. Sager, Progress in Physical Organic Chemistry , 2, 523 (1964). 2. B. Capon, Quart. Rev. (London), 13, 1*5 (1961+) . 3. A. Baeyer, C hem. Ber., 18, 2269 (1885). 1+. a) E. Vogel, Angew. Chem ., J2, 1+ (I960) ; b) Y. I. Gol'dfarb and L. I. Belen'kii, Russ. Ch em. Rev. , 29, 211+ (1950) ; c) J. D. Cox, Tetrahedron , 19, 1175 (1963). 5. S. Gabriel, Chem. Ber. , 21, 101+9 (1888). 6. P. Duden, ibid., 21* 1+77, 1+83 (1900); P. Duden and A. E. Macintyre, ibid. , 21* ^ 8l (1900); W. Marckwald, ibid. . 21* T&* (1900). 7P. E. Fanta in "Heterocyclic Compounds with Threeand Four-Membered Rings," Part 1, A. Weissberger, Ed., Interscience Publishers, New York, N. Y. , 1961+, Chapter 2. 8. J, E. Earley, C. E. O'Rourke, L. B. Clapp, J. 0. Edwards, and B. C. Lawes, J. Am. Chem. Soc. , 80, 31+58 (1958). 9. P. L. Southwick and •".. J. Shozda, ibid. , 82, 2888 (I960). 10. M. Prostenik, N. P. Salzman, and H. E. Carter, ibid. , XL> 1856 (1955) . 11. J. A. Deyrup and R. B. Greenwald, ibid. . 82, 1+538 (1965). 12. M. Karplus, J_l Chem. Phys. , J50, 11 (1959) ; J^ A^. Chem. Soc . 85, 2870 (1963); 0. L. Chapman and W. R. Adams, ibid., .89, 1+21+3 (1967) . 13. J. A. Deyrup and S. C. Clough, ibid. , 90, 3592 (1968). II4.. W. Kirmse, "Carbene Chemistry," Academic Press, New York, N. Y. , 19ol*. 15. R. H. Shapiro, J. H. Duncan, and J. C. Clopton, J_;_ Am. Chem . Soc. , 89, 11+1+2 (1967). 108

PAGE 123

109 16. J. D. Roberts, ibid., 22, 2959 (1951). 17. E. Mosettig, Organic Reactions , 8, 218 (1951+) . 18. D. Y. Cur tin, R. C. Fuson, and R. L. Shriner, "The Systematic Identification of Organic Compounds," 5th ed., John Wiley and Sons, Inc., New York, N. Y. , 1961+, 273. 19. G. Szeimes and R. Hulsgen, Chem. Ber. , 99, 1+91 (1966) 20. W. C. Baird, Jr., B. Franzus, and J. H. Surridge, J. Am. Chem. Soc. , 89, 1+10 (1967); C. E. Miller, J. Chem. Educ , kg, 251+ (1965); S. Hunig, H. R. Muller, and W. Thier, Angew. Chem. . ij., 271 (19o5) ; F. Aylward and M. Sawistowska, Chem. Ind. (London), 1+84 (1962). 21. P. J. Lillford and D. P. N. Satchell, ibid. , 1750 (1967); J. M. Briody and D. P. N. Satchell, ibid., 11+27 (1965); P. J. Lillford and D. P. N. Satchell, J. Chem. Soc , 360 (1967); A. Tille and H. Pracejus, Chem. Ber. , 100 , 19o (1967). 22. S. N. Foner and R. L. Hudson, J. Chem. Phys. , 28, 719 (1958). 23. J. Thiele, Ann. Chem., 271 , 127 (1892); C. V. King, J. Am. Chem. Soc , 62, 379 (191+0) . 21+. . E. J. Corey, W. L. Mock, and D. J. Pasto, Tetrahedron Letters , 3I+7 (1961). 25. H. Paulson and D. Stoye, Chem. Ber. , 99, 908 (1966). 26. C D. Hurd, "The Pyrolysis of Carbon Compounds," The ChenvCatalcg Co., Inc., New York, N. Y. , 1929, Chapter 1". 27. R. Buyle, Helv . Chim. Acta , 1+2, 21+1+9 (1961+) . 28. a) V. F. Martynov and I. B. Belov, J. Gen. Chem. USSR , 21, 1398 (196l) b) A. Padwa, J. Org. Chem. , 2P_, I27I+ (1965); c) N. H. Cromwell, N. G. Barker, R. A. Wankel, P. J. Vanderhorst, F. W. Olsen, and J. H. Anglin, Jr., J. Am. Chem. Soc, 22, 101+1+ (1951); N. H. Cromwell and H. Hoeksema.' ibid. , 21, 716 (191+9); N. H. Cromwell and R. P. Cahoy, i bid. , 80, 5521+ (1958). 29. L. Horner and E. Spietschka, Chem. Ber. , 89, 2765 (1956). 30. J. H. Hall and R. Kellogg, J. Org. Chem. , ^1, 1079 (1966) 31. C. A. Grob, Bull. Soc. Chim. Fr. , I360 (I960). 32. A. Furst, R. C Berlo, and 5. Hooton, Chem. Rev. , 51 (1965). 33. H. Staudinger, Ann. Chem. , 356 , 51 (1907). 31+. J. C. Sheehan and E. J. Corey, Organic Reactions , 9, 388 (1957); JA. Moore in "Hetercyclic Compounds with Threeand Four-Membered Rings," Part 2, A. Weissberger, Ed., Interscience

PAGE 124

110 Publishers, New York, N. Y. , 1964, 917-950; A. K. Bose, •G. Spiegelman, and M. S. Mannas, J^_ Am. C hem. Soc. , 90 , 4506 (1968); E. J. Corey and A. M. Felix, ibid. . 87, 2518 (1965). 55. J. C Sheehan and K. R. Henery-Logan, Ibid. . 79, 1262 (1957); Ibid. . 81, 3089, 5838 (1959). 36. a) G. Sunagawa and N. Yoshida, Yakugaku Zasshi , 82, 846 (1962) as found in C^ A_;_, 58, 5649; b) 1. L. Knunyants and N. P. Gambaryan, Bull. Akad. Sci. USSR . Djy. Chem. Sci. . 355 (1957) . 37. L. J. Bellemy, "The Infra-red Spectra of Complex Molecules," Methuen and Company, Ltd., London, 1962, 215. 38. A. K. Bose and I. Kugajevsky, Tetrahedron , 23, 957 (1967). 39. F. F. Blicka and W. A. Gould, J. Org. Chem. . 23_, 1102 (1958). 40. C L. Moyer, Ph.D. Dissertation, Harvard University, Cambridge, Massachusetts, 1968. 41. H. Staudinger, H. W. Klever, and P. Kober, Ann. Chem. . 374 . 1 (1910). 42. T. C. Bruice and S. J. Benkovic, J. Am. Chem. Soc . 85, 1 (1965). 43. JA. Deyrup and C. L. Moyer, Tetrahedron Letter s. 6178 (1968). 44. W. J. Gensler and J. C. Rockett, J^ Am^ Chem. Soc, 77> 5262 (1955); W. J. Gensler and W. R. Koehler, J^. Org. Chem. , 27, 2754 (1962) . 45. A. G. Hortmann and D. A. Robertson, J_^ Am. Chem. Soc. , 89, 5974 (1967); A. G. Hcrtmann and J. E. Martinelli, Tetrahedron Letters . 59 , 6205 (1968). 46. K. B. Wiberg and R. A. Fenoglio, JL Arn^ Chem. Soc . 90, 3395 (1968). 47. E. P. Blanchard, Jr., and A. Cairncross, ibid. . 88, 487 (1966). 48. H. P. Kaufmann and L. S. Huang, Chem. Ber. . 75B 1214 (1942). 49. J. H. Brewster and C. J. Ciotti, Jr., J. Am. Chem. Soc . _/7, 5214 (1955). 50. L. J. Bellemy, "The Infra-red Spectra of Complex Molecules," Methuen and Company, Ltd., London, 1962, 127. 51. N. N. Lichtin, Progress in Physical Organic Chemistry . 1, 75 (1963). 52. G. A. Olah and P. J. Szilagyi, J. Am. Chem. Soc . 91, 2949 (1969). 53. T. Cohen and G. L. Deets, ibid. . 89, 3939 (1968); R. M. Lusskin and J. J. Ritter, ibid. . 72, 5577 (1950). 54. N. J. Leonard and L. E. Brady, J. Org. Chem. . 30, 817 (1965).

PAGE 125

Ill 55. S.J. Cristol, F. P. Parungo, D. E. Plorde, and K. Schwarzenbach, J± Arn^ Chem. Soc , 82, 2879 (1965) . 56. I. Lengyl and J. C. Sheehan, Angew . Chem. . J.t 25 (1968). 57. G. A. Olah, Chem. Eng. News , ±5 {Ik), 77 (1967). 58. G. A. Olah and J. M. Bollinger, J^ Arn^ Chem. Soc. , 89, I4.7l4.l4. (1967) . 59. G. A. Olah, S. J. Kuhn, W. S. Tolgyesi, and E. B. Baker, ibid. . 84, 2733 (1962) . 60. D. S. Payne, Quart. Rev. (London), 15, I73 (196l) ; E. E. Aynsley, R. D. Peacock, and P. L. Robinson, Chem. and Ind. , 1117 (1951); G. A. Olah, E. B. Baker, J. C. Evans, W. S. Tolgyesi, J. S. Mclntyre, and I. J. Bastien, J. Am. Chem. Soc , 86 , I360 (1964). 61. R. B. Morin, B. G. Jackson, E. H. Flynn, R. W. Roeske, and S. L. Andrews, ibid. , 91, 1396 (1969). 62. J. C. Sheehan and J. W. Frankenfeld, J. Org. Chem. , 2J, 628 (1962). 63. F. W. Fowler and A. Hassner, J^ Arn^ Chem. Soc. , 90, 2875 (1968) ; N. J. Leonard and B. Zwanenburg, ibid. , 89, I4.I4.56 (1967). 64. L. A. Paquette, "Principles of Modern Heterocyclic Chemistry," W. A. Benjamin, Inc., New York, N. Y. , 1968, 95. 65. A. D. Holley and R. W. Holley, J. Am. Chem. Soc . J2, 2771 (1950); 21, 2124, 2129 (1914-9). 66. J. M. Coria, Angew. Chem. . J, 570 (1968). 67J. M. Conia and J. L. Ripoll, Bull. Soc. Chim. Fr. . 755, 763 (1963). 68. J. M. Conia and J. L. Ripoll, ibid. , 773 (1963). 69. R. Breslow, Angew. Chem. , 2> 565 (1968) ; R. Breslow, Chem. and Eng. News , 43 , (26), 90 (1965); R. Breslow, J. Brown, and J. J. Gajewski, J. Am. Chem. Soc , 89 , 14-383 (1967); A. Streitweiser, Jr., "Molecular Orbital Theory for Organic Chemists," John Wiley and Sons, Inc., New York, N. Y. , 196l. 70. T. Curtis and F. Schmidt, Chem. Ber. , 5.5, 1571 (1922). 71. H. J. Dauben, Jr., L. R. Honnen, and K. M. Harmon, J. Org. Chem. , 25, 11442 (I960); R. Damico and C. D. Broaddus, ibid. , j51, 1607 (1966); H. J. Dauben, Jr., F. A. Gadecki, K. M. Harmon, and D. L. Pearson, J^ Arn^ Chem. Soc . 29, 4557 (1957) • 72. H. L. Holmes, Organic Reactions , jfc, 60 (1948) ; J. Sauer, Angew . Chem. . 6, 16 (1967). 73. E. Grovenstein, Jr., and D. E. Lee, J. Am. Chem. Soc , 25, 2639 (1953) S. J. Cristol and W. P. Norris, ibid. . 25, 2645 (1953).

PAGE 126

112 74. K. D. Berlin, L. H. Gower, J. W. White, D. E. Gibbs, and G. ?. Sturm, J. Org. Chem ., 27, 3595 (1962); G. S. Hammond and J. T. Rudesill, JL Anu C hem. Soc , _72» 2 ^69 (1950) . 75. E. Jones and P. D. Ritchie, J. Chem. Soc , 4141 (1960). 76. R. D. Swigert, Ph.D. Dissertation, Harvard University, Cambridge, Massachusetts, 1964. 77. T. Cohen and G. L. Deets, JL Am. Chem. Soc. , 89 , 3939 (1967) ; D. F. DeTar and C. Weis, ibid. , 79, 3045 (1957). 78. B. R. Brown, Quart. Rev. (London), 5, 131 (1951). 79. A. I. Vogel, "Practical Organic Chemistry," 3rd ed., John Wiley and Sons, Inc., New York, N. Y. , 1966, 332. 80. R. Huisgen, Angew. Chem. (Int. Ed.) 2, 633 (1963); 2, 565 (1963); 7, 321 (1963); Proc. Chem. Soc , (Oct., 1961), 357. 81. P. B. Woller and N. H. Cromwell, J. Heterocyclic Che mistry. 5, 579 (1968). 82. R. Graeve and G. H. Wahl, Jr., JL Chem. Educ. , 41, 279 (1964). 83. A. Michael and L. M. Norton, Am. Chem. J., 2, 11 (1880). 84. J. R. A. Pollock and R. Stevens, Ed., "Dictionary of Organic Compounds," 4th ed., Oxford University Press, New York, N. Y. , 1965, 914. 85. R. Capeller, R. Griot, M. Haring, and T. Wagner-Jauregg, Helv. Chim. Acta. 40, 1652 (1957); M. A. Stolberg, J. J. O'Neill, and T. Wagner-Jauregg, J. Am. Chem. Soc , _75> 5 °45 (1953). 86. 'A. Zilkha, E. 3. Rachman, and J. Rivlin, J. Org. Chem. , 26, 376 (1961). 87. J. R. A. Pollock and R. Stevens, Ed., "Dictionary of Organic Compounds," 4th ed., Oxford University Press, New York, N Y. , 1965, 308. 88. T. L. Gresham, J. E. Janson, F. W. Shaver, R. A. Bankert, and F. T. Fiedorek, J. Am. Chem. Soc. 7$, 3168 (1951). 89. P. L. Southwick and R. T. Crouch, ibid. , 75, 3413 (1953). 90. E. J. Corey and M. Chaykovsky, ibid. . 87, I353 (1965). 91. A. J. Speziale and E. G. Jaworski, J. Org. Chem. . 25, 728 (1960). 92. J. R. A. Pollock and R. Stevens, Ed., "Dictionary of Organic Corapounds," 4th ed., Oxford University Press, New York, N. Y. , 1965, 372. 93. H. Roehnerc, Arch. Pharir.. . 295 . 697 (1962).

PAGE 127

113 9k. J. R. A. Pollock and R. Stevens, Ed., "Dictionary of Organic Compounds," lj.th ed., Oxford University Press, New York, N. Y. , 1965, 2689. 95. U. V. Moyer, Master's Thesis, University of Florida, Gainesville, Florida, 1968. 96. M. S. Newman, J. Am. Chem. Soc , 5J_, (1935). 97. D. Y. Curtin, R. C Fuson, and R. L. Shriner, "The Systematic Identification of Organic Compounds," 5th ed. , John Wiley and Sons, Inc., New York, N. Y. , 19bl+, 129. 98. A. I. Vogel, "Practical Organic Chemistry," 3rd ed., John Wiley and Sons., Inc., New York, N. Y. , 1966, 33^. 99. J. F. Norris and R. C. Young, J. Am. Chem. Soc , 52, 753 (1930). 100. R. Adams and L. H. Ulich, ibid. , kg, 599 (1920). 101. L. F. Fieser and M. Fieser, "Reagents for Organic Synthesis," John Wiley and Sons, Inc., New York, N. Y. , 1967, 1276.

PAGE 128

BIOGRAPHICAL SKETCH Stuart Chandler Clough was born July 29, 19U3, In Richmond, Virginia. In June, 196l, he graduated from Douglas Southall Freeman High School. In June, 1965, he received the degree of Bachelor of Science, with a major in chemistry from the University of Richmond. In September, 1965, he enrolled in the Graduate School of the University of Florida where he studied as a NASA Trainee (1965-1968). He then obtained a Graduate School Assistantship (1968-1969), followed by a research assistantship (1969-present) while he continued his study toward the degree of Doctor of Philosophy. Stuart Chandler Clough was married to Helve Viitel in August, 1968. He is a member of Phi Beta Kappa, Pi llu Epsilon, Gamma Sigma Epsilon, and the American Chemical Society. Ilk

PAGE 129

This dissertation was prepared under the direction of the chairman of the candidate's supervisory committee and has been approved by all members of that committee. It was submitted to the Dean of the College of Arts and Sciences and to the Graduate Councils and was approved as partial fulfillment of the requirements for the degree of Doctor of Philosophy. September, 1969 Dean, Coll Supervisory Committee: Dean, Graduate School 7^ //. Z„.ltldvr