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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.