CHEMISTRY OF AZIRIDINES
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
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 ,,'-
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
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 !;..,
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
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
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.)
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
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' . . .
Acid lHydrsZide (9I DI' ...... 9j
t 1-Benz l---hzr Ldlnec3rbox''lic
Acid Hydra:ide l(j C :D1, . . 9
rci d IHydr :ide (J ) CDCl, . . .. 9
F;PEC r (cont'd.i
Acid HyJraz de-A.cecone
hydrarc.ne (I '
Acid Hyvra-zide-AceC ne
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)
Methyl-2'-AzetidinunE l .
Methyl-?-A.ertidinone (c 9)
17 if l I -1-t-Bu I .-CI lor ':-4-
18 TrIns- I--Eutyl-.-Chlorn-'.-
MHehyl-2-.-':etldtnone ( )
. . . 101
. . . . 101
. . . . 105
C DC I
. . . . 99
Pj.e I a.
19 1-t-Butyl-.-:X ridiJhnce (5(.
E2 1- L-Butvl-2-A-zir J incc re ?-.' :I ic
21 Ci;-l-t-Buryl- ,-ftthl-2-
Azsbicycl. [ 1.1.0.] Pucrnc-
2-One C3tion (j
2) Tr'ns-1-c-L,-I. -,--flethyl-L-
Azlrldin.-c i -s ./ ic
24 Trans-l- -Burll-4-fIrh. '1-1-
Azabic/clo. [1.1.o.] Rutane-
2-One Cjr ion (5)
BIKGPJ.FrHliCsL JlCH ......
. . 107
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
Stuart Chandler Clough
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
noc generate the 2-aztrlne, but Instead 1-c-bucyl-2-Erlphenylmechyl-
aztridine and IN--buryl-triphenylmeLhylmeLhylamlne. The mechanism of
this reaction is discussed.
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
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.
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
I) E13t Ro-t. IOCH
RCHBrCHBErCO2CH3 ) J 7
2) R'NH2 1
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.
O" CH3 O A CH3 H urhChc2C
S 0 H 2
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.
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.
Vicinal Couulln& ConstJncs oa ArrldLne and AzetidnL e Pri .Lr. Protcr,
Co unJ (Ht; J OCn)
Ctmicund ls crsns
CH3 ,OCH3 ., 2.4
CI O 5.1 1.7
.I C' 5.0 2.1
REARRANGEMENTS OF 2-AZIPIDLUECARBOX/LIC
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-
thetic route fc.r formation of
after Roberts' synthesis of
the aziridLnecarboxaldehydes was pa~cerned
cyclopropanecarboxajdehde e () using the
SOC2 H 2rIH 21120
e T PJ H NHTs
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'.).
H2lNH2 H20 I-BuNHH2CH2 C HC-NHNrH
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.
7 OCH3 H2NNH2 H20
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
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).
7/- OCH3 H2NrjH2 H20 NHNH2
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.
7N 7AMNHNHI2 \
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.
7' OCH3 H2N IH2 H0
N7 OCH3 H2NNH2*H20
A2 NHIN H2
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 ()).
H HI0 H
C6H5CH2 NHCHHC2CH2C02CH3- [C H CH H 2CH CH2 C H 2CH ] CI'
NHNH2 H2NM H2H20 0 C6H5NHCH2CH2CONHNH2
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 ,
* 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
N' 65 H2NNHq H20
7"" 0 H H2NNHZ H20
N --- NO REACTION
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
C6H NHCH2 CONHNh'H2 C- O NO REACTION
65 2 2 a
C6H5 CH2tiCH2CONHNH2 C--H3H ) REACTION
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-
RrlHCH2CH=C=0 --- RNHCH2CH2COX
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.
*I + 0r: C6H5CH2CNHCH2CH2CO2CH3 + 0frHnH0
CHZCH' 26 IB 27
Silj H CH30H
-H H2 C TBul JHCHCCrlGCO, H + lJNHNHJ
IB + rj H20
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.
- 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.
--- C=C=O -- HN-NH -- P
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).
R H- 25
)R Fi NHCH2--
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
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. -
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-
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
(route B) closure to the pyrazolidone has also been suggested. The
question remains, why do epoxy and azirldinecarboxylic acid hydrarides
react so differently?
R OC2H5 2 H5R
S 34 -h 0 OH
T aN .
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.
R Ts 'N R
38 39 OH
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.
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). ''
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
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-
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.
Tn.: 6r.cturEr of the j ertdlninn (Qi3) ar sjilned o-n [te baais ci the
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 .'
CI 0 Cl 0
-.--- -- CH 1.... ....b
Th J b
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
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
OLi HCI -HCI
N I 1-BuHlCH2ICHCICOCI
i-Bu C2 t-Bu
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.
O/ONa (COCI)2 C'C
0 t(CoCI)2 r'O0a
E IY, N '
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 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
X y L>i. oH
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
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:
CI 0 N+
i-Bu R '^
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-
T-Bu I '
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. '-
SO2 1H32CH2CH 2
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
Ring Strain in Three-Membered Rings
Compound Strain Energy kcal/mol
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.
C OCI02 CL 0
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).
+ -f0 -
R- R f
* 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
Losyl carboxylic acid anhydrides have been isolated, and there is
precedent for their existence as reactive intermediates in some rearrange-
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.
R OS A CI 0
-B ,H R0 Nt-B
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
* 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
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,.
Cheruic3l Shlits (b.. Ln Sultur Liic.-.i Fl ar. ticc. External
Tetrame Lhyls l ne in Carbon TEtrachlri 3e
-1- 0B 1 0
.B. u JH
aCounrerion = toylate.
bCounLerton = n,.,late.
CDiiffrence in chEmical Ahtics of anhydride 7IZ and averaEe of Ions
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 (_ .
0 0 +
0- rSO2CI SO r AO
I-Bu L -Bu
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.
S-2. H 0 EvlJCI
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).
ChEmical Shitri (5) in uulur iloxide Relactve to Exrernal
Tecramethylaitlan in Cjrbon Tetrachloride
- 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.
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.
R=H, 73 a
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
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
sulfur dic-ide rules cut any concerted ,eitnondo.imic t in exp.niton
of the anhydride
X CI 0
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.
R O. tl
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.
H-0 R I B u
c B i P R
58 Cl 0
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-
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).
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 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)
50 sOI' F5
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.
C O 0
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.
N2 S Cr C1. S 42
t0 2A CH20Ac 2c
kCH O~c O' c
H 20 Ac
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-
2C- 2 20- Ts C1 2Cnc-I.0% + -CO + ObT
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.
N N CO + OTs
-Bu t -Bu
- 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
Apparent Second Order PRe Constanri for Hydrolystsl A
(0.5 11 I CH1/65'. Ethriol, 50)
ound 10 -2. (Iicer-mol-lsec)
CrON H 0.4
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.
s77A 0N a
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.
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-
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-
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
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.
O C H-'
C Bu -Bu
CH/' t-Bu -Bu
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
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.
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
S N-t-u (
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.
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'.).
JOC C 0 3 C03
I-Bu C66 1-Bu
I- Bu i-Bu
+ T-BuNHCH2 C'3
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.
,7' '0003 B -.C- 2
B ';-;'. COp
91 +c3 C
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_
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
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.
r 3OC03 3C0CH +
1 CH OH 3COCH +
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
1 CC 6
-f 0C3 C03 i-SuCH Bu H
7r7 Ni-BuJHCH2C03 + H2C=O
i C6H6 I
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.
H CCI4 C C
.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.
^ OCO s- ..C03 H t ,OC03
X-. -------- N
S0 i 0
CI-u 20 C3-
H 2CO t- lu JHCHC2,3 N- 'C?3
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',
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,
2. -DlbronobuLyrtc Acid
This was prepared according to the procedure of Michael and
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-
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
(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
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
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
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.
Fcund. C, 67.59; H, 7.41; N, 18.21.
l-Phenyl-?-Azirldinec rbcyylic ,ci d livdrazide-Acetcone
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
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-
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-
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
-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 );
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.
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.
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
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,)
(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
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.
acetic clid hy-rizide ( .'j; mp 125-i2L 5. (Lic. l2o. 9), ir (nujol)
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
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.
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
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,
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
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-
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
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
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
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
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