Some Spectral Properties and Chemical Reactions of Oxazoles
t- ÂogLNDE
SOIvB S?ECTF.AL PROPEC.TIES A\D CIDXICAL
REACTIONS 0-'T OLAZOI,ES
A Tl:esis
Presented fcr the Degrree of
Doctor of PhiJosophY
in the
UfIT\TEFSIÎY OF ADELA]ÐE
by
,ÞA-üt F " DOitAGiIüE, B.Sc. (iIons")
Depa:'tnént of Orga:ric Ohemistry
Decenber, 1968, MRssRc¡lusETTS lNsrtrurE oF TEcHNoLocy DEPARTMENT oF CHEMISTRY g¡. 56_025 CAMBRIDGE, MASSACHUSETTS O2I39
July 25, L969
The Registrat Unfversity of AdeLalde South AustraLfa 5001
Dear SLr:
I arn pleased to gLve rny conaent for the Barr SmLth Llbrary to allow the borrowlng and photo-copyLng of ny Ph.D. thesla, ln accordance wlth the llbrar¡i rules. Sincerely yours,
caa Paul Donaghue COI'TIEN'IS
Page
SUir'iir,lFJ \ai sr-riEiiú'N! t'aaj
}CIO{O'i'LNETE}.IlS t avl
PUBLICJTTIOì'IS (v,)
T{!'R.OÐUClIO}I 1 rr-j LìTEìÐ .ì Spe Oxazol-es" VI1ru^ .u¡L ¡ c Mass ctra of
¿¿lol In'¿rod.uc'l;ion 10
.aa I èZ- Basic FragnentatÍon lVlodes of Oxazoles 20
1"3 Siceleta-l- Rearra::genent Proce sse s
Involving B ron:ine lvfi grati-on )v
Skel-eta-l- Rear.ralgenent Processes frwoivinA Phenyi or iliei;hyl- Group }Íi-grations )7 cH.AJmR 2. )iuclear lfaqnetic Resonance S TA of Oxazcles"
AE Zø^¿ I Introð.uciion
2"2 theoreiioal C al-cul aiions 77
¿-o,)õ7 t\i ucle a:' lf agnetic Resona::¡ce Specira &)
-ci'Tqii) arY. j ,\ 7 O; 74 109 )oa Res';iis a-trd. Ði scussi on Page EXER]IvtrllITAL Genera-l- 115 CIIAPMF. 1" General 117 Preparation of Aceloins and- Acel-oj-n E sters 111 Preparation of Oxazoles lt> Preparation of Isotopica-lly LabelJ-ed- Cornpowids i2)+ rì-J.\-Jircf z vif-'u .ry!! J c 130 â 27 -{rfä}DIX '?. t)) APPE\DI( 2" 1)t ¡ÐnFxtTl-i-y z 1)+5 :!LþltvüL )e ¿¡ t ?"I.F-'EREI[C,ES ¡+u sulilI-ARY o the electron-irnpact ind-uced- rtagneni,ations of oxazoies have been measliÏ€- stud-ied- i'rith the aid. of deuteriu¡n iabelling arld. high z'esoiution lhepositionofanal-lrytsubstiiuentcontajni:rgthreeorrnore riass carbon atoms carr be c.etermrned- from the mass spectr,:nr, a:id the group is present' spectrurn also shows characieristic peaks if a 5-me'Lhyl show ihai The spectra of oxazoles specificaJ-]y ìâ'oelieO' lvith C'eute;:-r¡n -'Ì'e a hyarcgen attachec. to ihe o-xa.zoLe ring is no'ú rândomised' rvith hyorogens on a meihyl or a phenyl subsiituent, and- ihat the lri{co" involve fragnientation observed- in the spectra of many oxazoies does noi a hyd.rogen attached- io the oxazoLe ring' (:ii-co A pathrvay has been posiulated. for -rJ:e initiai fragrnentati on , borc r,/i4rIo") of the oxazoLe rfug, rvhi-ch ir¡¡okes creavage of the 1-2 substitueni folio.,",æd by loss of co rvith concornitar:-i, n:-igration of the c-l is l-os'ü -tc c41o If the fragrnentation process is ì,i4ilo", ahydrogen atcn froni a substii;ueni concurrentiy l'¡ith the exp''lision of C0" the nass spectra of d.i-pheryi-oxazoles shov¡ a peak a*, g/s 16J (C"-A^rh.r")r'uheformationof'¡'hichdernandsaphenyirnigration"This t) ) peù,: g/e 161 is promi:rent in the si' trra of 2'5- ¡1-:'ð' ['l-d'ipÌren-¡iorazoJ-es' but ninor in the spec'iJru;n oÎ 2rçlt-,ñerryloxazoLe" Deuterj--un l-abeii:-ng studies enableC. tne d.etection of -;;-c a-l--ueílate i'earra::genen't pa1;l-va'Vs cí' ihe for"raticn iTi'¿ne spec-ür'ijin of 2rt¡{2-tnpirenSt--i:xazoLe" 'A' coniparisol: (ii) of tlre peak at úS 165 in 'uhe spectra of stj-lbene arrJ- ! r10-d.i-ttyd'ro- 'i,lee pJ:enan'uhrene, r'ri-tJe its forrnation j¡l spectra of d'iphenyloxazoLes' shows 'uhat a coünnon mechanis^tr d-oes not opera-r,e in the heterocyclic arrd' ca-:"bocycJ-ic sYstems . lhenuc]-earmagneiicresonancespectraweredeterrninedfora n¡nber or oxazoLes, and some correiations establ-ished. beil'reen the cherriea]- posi-uion of shift a:r.d. splì.tting patte:r: of a methyl resonance, and the substi.uution of the methyl groupc solveåt shift stucjies aÌso proved- art oxazole" of some vafue in d-eternri:ring the substituiion patiern of the magnitud-e of the solvent shift for the meiJ:yl resonance of neihyÌ oxazoles v¡as fourrd- to be strongly d-ependent on -r-J:e composi-tion of of solute. ihe solvent, but independent of the concentration ,Examina- tion of a nurrber of d-iffereni -types of polar soluiès showeC' that in al-1 -r'he cases the magnitud.e of the sol-vent s."rift lvas i:rdeper'd'en-t' of concen- tration of solute" Some preliminary suggestions have been adva-nced' io accor¡rt for ihis observ-ation. a.'leyd-rid-e to allyl _A. stui.y of the Diels-A]der ad.d-iiion of rna-leic oxazoi-es i¡rC.icateO- that the ad.åition proceeds viz xt end"o-tramsitj-on state, vrith an angle of aporoxijlla'üe] y 60o b"too"en ihe pl-a-ne of the oxazole and. dienophile" the inertness of aryl oxazoles to cycì-o- ad-d-ltion is ascribed. to a]"I electron:c rather ihan a steric effec-b" ( r-r-r-) ST.{TE}ENT. This thesis contains no material- which has been acceptec. for the award. of ariy other d.egree or d-iploma ín eny uruiversity, a¡rd. to the best of my knovùed.ge and- belief contai¡l5 no materiaf previouslJ¡ published. or written by arroiher person, except v¡here d.ue reference is mad-e in the -t ext. ( al'J I wish to tha¡rk most sincerely Dr" H"J. Rocrda for his gu-idance arrrl encouragenent d.uring supenrision of this v¡ork" I aro ind.ebted to Dr. J"li. Bowie for helpfu-l- suggestions a]1cl" sii¡ruiatj¡rg C,iscussion on ma-ss spectral problems, to Dr. T'lrÍ' Spotst"'ood j:r for hrs suggestions as to the interpretaiion of solvent shj-fis the IIoII}¡Io spectra, arrd. to Mr. BÐ.. Roney for assistarrce v;ith computationa.l problems i.:e the tlreoretical ca-1cirl-atíons" I am grateful- to L{r. R.L. Pa-ltrid.ge for record-irrg the n.m"Ï'" spectra, and. io Mr" D.ts. cobb for àetermining some of the mass spectrae This research rtras carried out d.uring ihe tenr:re of a Con¡nonv¡eal-th ?ostgrad.uate A'rca'd., wluich I gratef',:lly aôlcnov'ùedge' (") PUBLTCAÎIONS. Part of the work d,escrlbed. in this thesis has been publishei' in ihe folloiving Papers: "Îhe lVlass spectra of some A1)qÊ and. Aryl Oxazo1-esr[ Bor¡,,ie, Jü., Ðonaghue, P"!'. ¡ Rodd.a, l{"J., Cooks¡ R"G. ¡ 13. and. l'f i-l-Iiârns ¡ D.H. ¡ J illass ., 1968, 1, nThe crr|{, skeletal-reaffaflgement Fragment in the }lass Spectra of HeterocycU-c Systems Containing Diphenyl Substituents. A Deuterium Labelling Siud'yrtl Scnvie¡ J.H., Donaghue, P.F. , Rodda, 71.J .2 artd' Sjmons, B 'K; ' Teiralredron, 1968t 4, 3965. Î(TRODUCTION Inrecentyearstheadventofthehighspeedcomputerhaslecrto of a renerved. interest in i;he theoretical d.eriva-r,ion of the properties organic mol-ecufes. I\fuch of this 'lvork has been concerned' with hetero- as a resuft, there has been an increased c1¡rcLio aromatic =y"t"*"r1-L "rtd interest i:r the properties, particularly spectra-l properties, of these cornpourrds o tr ^In suggested. the generic na¡r,e axazol-e for cornpounð's . 188J Hantzsch' containíng the nucteus (1). IIe al-so proposed a l-et'cering system (1a) to ind.ica-te the position of substitution but, in all but the oId-est refer- ences, this has been supersed.ed by a nrr"nerical system (t¡). 7 N 4 N ) \ a p 0 0 0 I (r ( 1b (r ) ") ) Although on-1y one naturaliy-occurring ccrnpounC. has been formd- io f-7 contain tl¡e oxezole nucleusr" / oxazol-es can be prepared' fron g-a:ni¡o oq acidsro u.td- frora proteinsrT and' a:ee thus chemicdr-Iy relateå to a iarge 10 m¡nber of natr:ra] Iy-occr.rring compound.s" It has been suggesteð'" that oxazoLe r:nj-ts may forrn part of proteù mol-ecuf-es, but this suggestion has not been subste¡rtiated.' The first krown preparation of an o>iazole 1l'as Ay Zlniil in 16t'p. Iïe obtairred-, fron the reaction of benz)-f. with al-cohol-ic a.rrronia, a- con- 2 poìirl¿ which he ca-l-led- zzobenzlL., a:rô which Lu.ureni1 L^t"" na¡ned- benzji-a*n. In'1881 J"pp1J p"opo="d. the structure 2t4t5-tttphrcrryLoxazofe (Z) for azobenzr]-¡ a'd- this assj-gnmenì; was confirmed in ,937''4 Jappus pro- posa-l represented- the first post-*lation of ib'e oxazole ring systen a-s a structr:ral entityr aJd. six years later an indeper.deni series of obser- vations 1ed. Ila¡tz="h15 to an id.eniica-l- formu]-aii on of t]ne oxazole nucleus. cgH5 N R C O cH í'rrlH co d RCON HcHR'CO2R" Ro-.fi, allq¡I, a:¡r1 R" a.liVl, zry! csH5 coH = U s / _\ (z) l)) (u) Dr_:ring iàe j:ritiaJ- developrent of axazoLe chemistry. ¡ e large ¡/ nuinber of s¡rntheij-c routes io the rj-ng system ï¡as evolved.'o the rnosi general of these a:'e the Robi:rson4+abriel s¡mthesis, the Davidson cyclj-sation, the Harrtzsch s¡"nthesls, ancl t]re Fischer conclensaticn. 4'7 4 l\ rn tÀe Robinson4abriel s¡rnthesisr /t¡c ¿rr g-acJ¡Ia'ninoketorLe 3) or c-acylami¡oester (l+) is cyclised- by treatnent with a strong d.ehyd.rati:rg ¡gei-rtr usuatly concentrated- sulphuric acid.ror phosphon:s pentachloriûe in chloroforîn" Cyclisaiion of (3) yleld.s trisubsiiiuted ot 2"5-dí' subs'iiiuied oxazoles (5) , vrhereas cycJ-isation of (¡) reaas to l-alkox¡r or !-phenoxyor-azoleu (6). Thc carbcn of the anid.e carbon¡rJ- in (l) arri (.t) lecotnes C-2 of the oxzzof-e ring. R N N \ R R R RC 0 âJ-jryl ar¡tL TìË iî, e-11çy1' arYi R"- , (¡) (5) The fonnation of an oxazol-" (Z) by treaiing e¡r aceloin ester (B) rrith ej-ther amrnonia or a suitable ammoniurn sa-l-t, is lcoo-'vn as ihe pre- Daviclson oxazole s¡rnthesis.lÀ' This nethoê is ¡nost su-ited to ihe paration of trial-þl oxazoles (7, pilt-Rfi=a-llСl-), the cyclisation is stz:aight fo¡wa:-d., with the carbon of ihe keicne ca:cbonyl becoming c-l¡ of the oxazoLe ring, a¡d. the carbon of tbre ester åa.bony;-, C-2" R R-co-cH-R I ? + /a U R 0 R c0-RI R.8= a-l-þJ-, æYI (B) (z) the synthesis is not nor:nally ai¡pJ-icable to the p-reparation of 2- ù¡.substituted o>:azol-es (7, Ht Ji), C-ue to ihe C.jifi-culty in obta-i-ning ihe r.equired- aceioin fcrmates (8, R"i{)" An exception is the plrepaf'a- ticni9 o, 4"i-ôiphenyloxazoLe (7, P.=;.t *6n', R"=ii) from the reaC:iy benzoin formate (8, R=nt=Cr-4, Rrr=H) avaiJable e) " narrt:zscr/, .' obserr¡ed. ihai oxazoles v'rere forrned by the action of amid-es on d-ha-loketones. this s¡mthesis worked- wel-1 ivith substituted- amid.es and. d-iaryI or arylalþlketones, bui rvas unsuccessful j-f either forrnamid.e or arr g-bronod.ia-1þlketone was usedo l'fod-j-fications of ti:ê experimental procedure enabled Breð.ereck arrd Lérvry to syrrthesise 2- unsubstituted oxazoles (/, R"=H) by the acti-on of forrna.inid.e on d-brono- ke-ucnes.2o The reactj-on is, hol'rever" sti-ll hmited. to the synthesis of oxazoles cont¿anj¡rg at least one ar¡r1 substituent" Ini'ciaj-1;ø there v¡as some disagreement concerriing orientatj-on of the oxazoles prod-uced. by this method.rlT'21 '5'22 b-'- it j-s now well establish"d.17 tt'l"t the carbon carryi:rg the halogen becomes C-5 of the oxazole ring" À rnecha¡iis:n 20 (Scheme 'i) nas been proposed. for this reactir:nn-- Oxazo1.e formation is envisaged a-s proceeoing either by cyclisaiion of an j:riij-all,v-forrned- i-,rino e-tL,er hyd.robroniae (9), or by acylatj,on of the d.erived. aceloi:: (tO), ihen subsequent attack of thre amid.e nitrogen on the ketone carbonyi, foilor'¡ed by cyclisation" Cond-ensation of an a-ld-ehyâe c¡'ai13¡y¿r'i-n (1'î) vrith an aldehyd'e, in the presence of d.ry etherea-l hyd-::ogen chioriåe, leads to mod-erate yieicìs of oxazoieso this cyclisation was d-iscovered. 'oy Fischerr2l a¡C- he subsequenti¡r d.efined- the scope anc course oí ihe reaction. The -or.oduct (tZ) frotn the conC.ensation oi þenzefd.eh5rd.e cyanohyarin (11, R- C(l{=) rvi-th a:risaloehyae (1J), is the sane as obiaj.neC. by ihæ v-) tnat _fl D_ti v¡t.lTj._ vvara\ I Ír r\ î RilCOl,TlI I l1-- ^arwl.L -rr^ vv -Ð 2 I 0 BrI l_ rt-Dn c = NI{r' Br (g) R- Cli- c0-Rr R I OH a R U (ro) /' a/ R.. I n H RC0il-jl lj U 2 ï /t I o-- 0c-R Dtl ô^ c0 1.. R sclfl,m 1. c.eþd:cation of o-p-netho xybervoyLa.¡ninoacetcphenone (lr) "23 These r.esuits Aeíine the reaction pathivay (Schem" 2) , v¡i-ih the cæ-Þon of the ald.ehyC.e carbonyl beconi-ng C-2 oi the oxazole ring" It has been fo..¡nd -t",zt 205-d-r-(p-rnethox¡¡phenyL)-oxzzoLe (7, R=H, (11r R=p-Cií-O- Rî=p.r'=ÞCf,..O4/í-,)-"3- - 6-'tç :-s forned. from ari:sal-d-ehyC.e eya:rohyd.r'in ) Crîî.) and. hyd-rogen chJ-orid.e, in the absence of anì-saJd-ehyð,eo4+'25 *u o+ nf simila-2. results have been r.eporieù for otÌrer cya:roÌrydrins"tt This t 0ïi.,- ñ{ R-ci{(oH) - cN l' i c Æ-- c0 0c- c,H. OcH- (r r ) b5 bh - t - P L ( 1å_) p- cH_Ot -c o4Æ. cilo (ß) c^H- ocH oc o 6H4- 3-p (tz) SCIfr},E 2. i¡d.icates that, rrnC.er the reaction cond.itions' solle d.issociation of a cyanohyd.rJ:r into the a-ld.ehyde ar:d. hyorogen cyanid-e is possible. lhe synthesis (Sctreme Z) is, therefore, only rna:ribiguous v¡hen an aldehyd.e is conclenseC. vrith its ovnr cyanohyd.rin, even ihough the s¡mthesi-s nornially gives a honogeneous product. 'vÏithout exception, these s¡mthetic methods a-re most effeciive in the prepa:cziior^ af aryL and- poiyal-þl oxazoles" To obtain a rnono- substiiuted oxazole, it is norrnei-ly necessary'co first prepa.îe a.r esier of an oxazol.e carbo>:ylic acid. äyd-z'ciysis and decarboxylation of this ester then yíe1C-s ihe requJ-reô- prod'cici, À s¡,t^thesis (Scieene J) of -7- oxazole (i), frorn the o-iethyl ester of d.iJeydrox¡r,:raleic acid. (19), is an exampJ-e of such a proced.u "" "27 c(cn) c(on) UU - .ì H Ê ll äcOiIl2 N 2 L N co r" inz ," rH5 "o -+tic]. ( 0 ) cczc2 H 0 (1e) 5 (r ) scmlæ 3" the d.etaüed- chernical investigations v¿hich ultimaieiy l-ed. to the s¡rnthesi-s of penicillin, resuJ.teC- i¡t several- signiÍica:rt adva¡rces j:: oxazoie cheniisiry. A general synthesis of 2-monosubsiitutedL oxazoles (lg), v¡hich are often d.ifficul-t to prepare by other nethod.s, lvas F,ì sc d-eveloped. d.uring this stud.y"28 ft lvas founri that condensation of ari /.-\ i:rinoeiher (15) v-ith ethylglycinate hyd-rocirJ-orid-e gave en 2t -a-ikoxy- aiþlid-enaminoacetic ester (i6) vrhich corr-ld- be cyclised- to a 2-subs'tituted- J¡-carboethoxyoxazofe (t 7) . Normal- hyd.roiysis and d.ecarbo:ryiation then gave the required. oxazoLe (schene 4). the approach to the s¡rnthesis of penicrl-l-in a-l-so yiei-d-ed- severai ns,¡¡ reagents v¡hi-ch alloved- the Robinson-Gabriei meihoC. io be apol-ied- to the cycJ-isation of unstabie precursoriì o Even l'ith such a varieiy of rcu'ces avail,able for the s¡,:rtÌresis of oxazoies, there a:ce stil-I rnany d.eficiencies in our h:ovrled-ge of ihe cherisiry of 'che ox,¿zoLe systcn. r,','Iereas ihe ii:ysical pr.ope¡.'ci gs of R-C-Ont t*t CIizCo ------> rL v v¡l 2C;\ rl-rt 2 r tt 0R1 C0 ñ --; ltr-i-I ci z" t\ (1r) (r e ) co^c^H }I co tl5 - û^a\ f_i zc 2iL5 + ll T- H' N 2 Ì'j R-_C Ci]CK I -_+ -,+^ûu o- -r! 2tr5 0R3 R 0 (17) (r) KOH N \ (z) Quinoli-ae 0 R (r e) SCiDitrE l- c oxazol es a-re fairl-y well d.ocunented., little is lcrov¡n of their chenical reactions" Even such a cormon reaction as halogenation has noi been ful-iy Some oxazoles llave been fou:l¡i to rmdergo Diels- "i.rai"d,16'19 Al-ð.er ad-d-j-tion to give pyrid-i:re derivatives, but the scope of this reec- tion has not been fulty d-etermj¡ed"2? Cu:' lmowl-edge of ihe speetrai pr.operties of oxazoles is even mor€ r.eagre, bei:ig iurrited. to isolateC. reports of uftraviol-et absorpiiot"27'5O a¡d mass spectral- fragnerriair-ott21 ô the genera-l aj¡n of the vrork d-escribed- in this thesis was to investigaie more fully some of tJ.e spectra-l proper-lies and. chernicaf- reaciÍons of oxazoles. 1o tJris end., irrvestigations of the mass specira a¡rd. nuclear magnetic resonance spectra of oxazofes r¡Íere u.r:.d.ertaken" Ïn ad.d.ition the 1rJ-cyclcadd-ition reactions of oxazoLes have been'studied. c) trLr r¡ Ët¡ l' -10- OX.{ZOLES Iú,qSS SIÐCTR-A OF " 1.1 Introd-uction" lhe appÌication of nass spectrornetry ca:: greatly si'nplify the eiucid.ation of the siructures of organic inolecul-eso Tn ihe last decaÃe, higþ resolution measurenents and. isotopic labeliing stuC.ies, coupl-ed rvi1i: ai.vanced a:raJysis of spectra by kinetic tecl:nio;u..32 ot by <1 computer'-aid.ed. næthods"'- have ma-de possible the j:iterpretation of ihe fragmeniation processes of rnany t;4pes of organic mol-ecules. Detaiis of' the applicatiol-r of the lcnorvledge of norrnal fragmenialion p:'ocesses to sirrrctule-elucidation, as v¡el-l- as ihe instn:-rnentaiion a::rd. ¡nethod.s of 'zQ Zt mass spectrornei':y, a:'e availabl-e i:r nany bookJþ-tó anð revie'rvt"39tL'o I The raigratioir upon eleciron i¡rpacl of groups other tha¡r hydrogen has o::rly been tvidely'recogni-sed. rvithin the iast five y"*""+1 Such processes, terined skeletal- rearz'ellgeinent processes, are parií- cularly i:nporiant from a necl:la:ristic viervpoinrr a:rd. ihey ca.rnot a-s yet be precicted. rvith any degree of certai-nty. KnowleC'ge oÎ such Ðipcesses is vital- i.f r,re-ss specironetry is to be useci for struct'.;.¡'e- ' el-uci-oati-on" r the tenn t electron :-rrpacti j-s 'l;sed- throughout to Cenote the ionisation of a molecul e by a hrgh energy electron beam" It d.oes not in¡l;r a:-ry slecific ¡:echanisn for ihis process. 44 the occurrence of skel-eial teaYz processes places seYere 1i:i¿- 2 taiions on the ¡resent appl-icati-on of speeC. co:nputer t"."rr."¡....""1 for ihe arraiysis of mass spectra, wt-ie the rearrangement processes are preCr-ictable a priori" Skele-la-l reerrargernent processe generally faJ-l- in-Lo one of à¡¡o cl-assifications: - a) ihe type ABC -> + B, 'where A anC. C are o-¡i- ginally joi:ieC. orrl¡r ihroudl B; b) more compiex reorganisation of ihe inol-ecul-ar ion produces a spectrul v¡hich be¿::s titiie rel-ation io that expected fron a no-iecular ion stn cture based" oi: that of the ¡noiecule in iis gror.:nd- state" In general-, skel-eial rearrangenents occu-r rvhen sirnpl-e fragmeniaij-ons are r:¡favourable. Rearrangement processes of the âïre nore prevalent ',vhen sites of unsaturation in the vicinity bono(s) cleaved alforv fomation of eiiùer rad-ica] or carboniuin-ion centres, io '.',{iich a:r incipieni radical (or alion) ¡nay migra'ue. I{any of i;hre skeletal--rearraJl.geneni processes encou:riered i-n nass spectro:netry have j¡l corcmon 'une loss of a siable neutz'al noiety from a norr-teflrriía1 posiiion in ì;he originaf- molecul-e" Tbe conseq'ùence of such TeeiTarLgements, especialiy )Í 'chey occuï to a significa:ri ex'len'tr is the observaiicn in the spectr,:rn of lons coinposed of atorns l'/n:-ch r¡ere not bor¡nd- in a contiguous chain in the parent rnol eci:*l-c. Such resuiis rviii ptove nisieet''j-ng i.n the interpre-iatio:' cf specira, ru:Jess the scope of these rearrari3ernents is f'.:ily expioreå anC- d-el-inea-ted. 7t Because the Quasi-Equiiibriun 'ii:eory'- has sc fa:. ¡r'oveC. applicabie -12- orùy for the interpretation of the mass sÞecira of si-'npJ-e orga:úc molecules, groured. state theory ha-s been lvid-ely appS-ied. to ihe pred.ic- tion and- rationa-lisation of fragrnentation mod.es" It is fou¡:d- ttrait ttre major fragmentation pathways c¿ìrr often be rationali sed by assuning that fragmentation a-hvays occr.ìrs ihrougþ that for::l of the chargeC. species (cation or raCical- caiion) r'¡hich ha-s ihe posiiive cb,arge (and- rad.ical if preseni) in the rnost stable position" and by expelling " s-cable (or For example, a large protorbion of neutraJ- raàical-) "p""i"".LJ skeleial-rearra.ngements which are prod.uced upon electron impact are accompanied. by the expulsion of such neutra1 entities as carbon *ono***i6 carbon d.ioxid-e ,47 '48 fornald-ehy d. r49 hyd-rogen cya:rid.e ,46 '50-52 or nitrogenr)-')-)') al-t of ¡¡¡hich have either negativet or sma1l positive, heats of fonlatiorr.4l T.¡¡o techniques v¡hich may be r:sed to gain an i-nsigþi i-nto the refative strrrctrires of rnoiecul-ar or fragment ions t are the anal-ysis of shapes ard. abr:¡dærces of metastable peaks use of the ki:ieiic ihe ,42 ^d 6z 1-7 aprroach""-. Ii has been sho'¡rn'' ti:at if, in the ¡ra-ss s'cectrc::ietet, at: i-on of mass rnj d.ecomposes after acceleration, bui before entry i¡r'to the / analyse{, to g;y" a neutral- pariicle (or rad.ical) ar,,d ari ion of mass nrr / fri a d-oubIe focus mass sÐectroneier, meiastable peaks e-ï'e noï'- maJiy oniy record-ed. for decompositions r,'¡]rich occur jn the fieio- fnee region, beivleen ì;he el-ec'c;'ostai-'c a::.ô- magneiic seciors. -11- then a d-iffuse peak is recorðed- v¡ith a maxjmum intensity at ¡nass m", the val-ue of v/nich is given by equation (t). Ihese ions (n'F) are }r.cn'n a-s rneiastdcl-e íons, the j-on of mass m4 is iceor¡,n as the pareni a¡d. the loi-r of rnass m^ as the ôaugþter ion" ¿ m', = (^r)2/^o (r) a reta-siable ion for the tra¡rsition The presence of ^1- ^2 has been rega.::d-ed. as evidence that 'uJ:e species of mass (n - *Z) is l-osi -a as a single entity by a uni-rnolecul*" pto""=="'o Frequentiy this is cor.reci, as the atoms lost comespond to simple siable molec'ul-es such --as C^H^-z-2 a¡d- CO, or to weli-l¡aown rad.icaì-s tike CIír") e:rd- CIiO"o Examples are l¡rcrr,r:t, hotlever, Where a metastabie peak eXiSis for z d.eComposition ¡/ ¡õ v¡hich has been shor,vn to occur by a t¡,vo-step p;'oe""".)o-)o The presence of a r¡etasiabl-e ion foy'the loss of a unii does not, iàerefore: provê tirat the unit aì; a:ry time exists as a structura-l- entity in the parent rnolecule. It should. be kept in mi:rd. that althoug¡t rd' atò" m, arise from -ûhe sa¡ne ion (mr) tttey are foz:'ned. by tvro processes (^2W a fasi decomposition and- ¡n'' by a s1o,v deconposition of mr) rvhich are not necessariIy the "*n .56 '58 UsuaiJ-y inctastar¡le peaks have a shape resenbli:rg a Gaussian d-'i st::i-buti on cur,¡e, but occasicnal-ly t'l.ey are observeò to be broader a:r-à tc rrave areiativel-;r fiat tcp.5g ri has becn sro'¡'6o'5n' t:ra'c thris f¡1t-Lop effect is C^ue to tlie release of ]i:retic eÌ:erС in the C--ìsso- cíe-uion ol '¿hr¿ pa:eii't ion, anà the ldneti-c enez'g,' r'eiea-scci (T) is ,' related to the vid-ih of the metastable peah (a), tire accelerat-ing voltage (V), and. the masses of ihe parent (n,) ard. d.aught." (t ) ions accordir:g to equation (Z).60 +(^r)2 (*r - nr) r d. (z) m. n, ev I Since ions identica-l in str,,rcture and energy v,¡il-1 d-econpose fur ti:e sane .ttzy, i'v follov¡s thai if the metastable peaks observed. for the transitior *. .+ *2 h the specira of two coinpou;rd.s have d-ifferent shapes, ihe naiure of the ion of mass m1 d.iffers j:r each co¡n-oowrd-" It must be stressed, hov'rever, that the converse is not necessaril-y ttue" lhe observatj-on thai the ¡letastable peaJ:s for 'che above iransition have id.enticai shapes d.oes not, as has been ciaj-rn"do62 -orove that the ions of ma-ss m, are id-entical- j:r each comporxrð." this is especi-dr-ly true i-f the netasiabie peaks ur,C.er discussion have the norrnal- Gaussian sha5re. lhe abu¡r,Lance of a metastable peak will be relateò to the rate constant for the d-econposition giving rise to it.,lvhich will¡in turn, be d.ei:endent on the structu¡es aird. energies of the i-niiial- a:rcL prod-uc'c ;ons,.þ) * G). Thus, :.f the peak ai tS^, in the spectra of à¡,,o corn;oor:nrls is conposed" entirel-y of ions þ) , with the sa,::re enerry o_istr.i- buiion, ariå tne peak at of tS ^, ions (Ð , th"t the raie of c.isappearaÌ.r.ce of G) and- appeara¡ce of @) rviJ-f corresponrl Ín ihe two spectra, for al-i -15- vaiues of the ionising potential-"f the raiios of trese i'eactions may m, lil 'o--x/* 2¡*Í be equaiea "rø =""pecti-vely. it i;hen follovrs thai i-f, unò-er the above cond.üions, the ratio mô fi.'t/i*'ooes z/^* jn tne -vuo specira, bur th.e ratj-o noi, "or"esponds j:r compou¡ds pea-}< m2 corresr:onds entirel-y to (Ð tnen botìr ihe "t úZ arrd. arises only frorn þ) , but that 'the peak a-' úg *, consists in part, at feasì; in one compound-, of ions v¡hich d.iffer in eiiirer st-niciure or enerС d-istribution fro¡';t the ions þ) " m- m_2¡^"' Similarly, equivatence of 1¡*', b',,t noi of irrlàícates thai in both spectra the peak X tS *.i consisis entirely of (-e), but that, j¡. one compor.rnd-, so¡ne of the ions m, arise via another at l-east "t tS fraginentation pathway( s) . Such observaiicns are of great use j:r d.eciC.ing tvirether a comnon j¡.termeC.iate is involved- i¡ the íragnrentation of cl-osely related. compounds "52-64 ÀIthough tlie behaviour of rnany aromatic five-nenbered heteroc¡rclic ri:rg systens upon eleciron impact is wel-l- d.ocumenie ð.r37 u"ry littl-e ha-s becn reportec. on the inass spectra of oxazoles, O: f Ii i-s necessary io nake cornpa-rison over severa-l velr:es of -ul:e ionisi:rg voltage in order to eiiminate rarràon correlaiions' a a o REIÀTIVE ÀBUYD^IcE (f) È[:IÂTIVE ÂBIJ¡IDANCE (f) REIÂTIVE ÀBUI¡DÀilCE (f) o o Àø@ôoo I NÈ o o oo o ooo 1,5 t;' q5 foo ls t 1l o o + , T + -16- illusirateC by the spec.trum (l:-g" Z) oî 2-n-lnexyl,$-tr,eiJn}roxezoJe (ZO); wi'uh all the majo:: fragment ions being proôuced- by cleavage of the o)/r n-nexyl cnel-no vbrr5 coHS l\ì N vb¡ ¡5 csHs htt\^L)- csHS 0 0 0 \¿t ) (zz) (zt) The mass spectra of ìhd tirree isoneric d.j-phenyt oxazoi-es (2i, 22, 2:.) have been repcrted. a:-rd discu=="ô.uJX In each case the mol-ecufa¡ ion is ih" b"=" peal< of 'r,he spectrun, and the j¡ritial fragrnentation i s ¡{-CO-ï{CN" Such fragmentation C.enand.s 'chat each oxazoi.e i:nd.ergo extensive skel-eta] rearrargernent upon electron irnpact" À notable feature of tÌre spectra of these three coinpoi::tds is the presence of an Íon þ) g/e 16j (rrJrg, h"r,) v¡h-ich is a rnajor fragnent iir tÌre spectra of (21) ,:ra (ZZ) , but negl iglbr e in ihe spectrr-:r-ä (¡ig" l) at (zj). irormation of (c) is pronounced- rvhen l¡-,!-c.iphenylimid.az o- "174 "56 1- anå, 3rl¡-diphcnyLpyrezole'f ur" subject to electron impact, but is eithez' /- snali or does not occr:r in the specira of d-iphenyifr-¡ranso / a:rd. d.iphenyi- a- ,-:yrroìes.''^/ ft wo',:-l-d- appear i;hat ihe p1-esence of trvo hetero-ato;ns is essential- for the fornation of G) in d.iphenyi hetero-arornat'i,c systenso llechanisrns have been adva¡rced. for the Í'onnation of (g) froin (Zl) a-ïxi (ZZ) , but 'chey d.o not i-nvoke pa-:rticipation of the seconf. heiero-ai .^")1 -17- _J _ a\l-_ r\u_ ,r ¡-rT a -rf, li UII f/-n l./ W /;L-- CH- v¿I^ v /tL- ^ o)sii-- - - ^ o2/-jl- ^-Jb, '¿- o, cl- (+) @) (26) Îi:e f or"naiion of úS 165 nas been noted. j:r the specira of sevez.al hyd.rocarbons, notabl-y diJ.bene (2+) , 9 r1O-C.i-hydrophena:l'th:ene (t-t), a-r,c. 1-chloro-1 (26),68 Frorn a combrnation of "2-d.ii*renylethane 47 d.euieri-r.:rn arrd. ''C l-a¡"ll-ing stud-ies, and with the assumpiion thai l-oss of hyd.rogen chioride fron tÌre molecuiar ion of (26) gives rise to the molecul-ar ion of (Z+) , a mechariis.rn (Scheme !) has been proposed- to Ía accoi:nt for -r,he fcr-,nation of (S) frcn (24).'" T.ne frzg:nentaiion pathr,vays proposed- for tne fo::nation of (^d /Õ 24 fron the h;,rd-rocarbonoo ,rld. hete-rocyclic)¡ corn;oourid-s are very si-tcilar, ind-icating ihat the necha:rism of this rearrærge:nent Ìras been consid.ered. to be fai-rliy constant" Although this -is a:r a'¡tractive anC. unifying propositicn, explain the absence of a peaJ< i65 v! it fails to "t úS the spectra of inany diphenyl arornaiic conporrnd.s, lr4rich a-re appaJentl-y v,'e-l i sui-teC. to u:r,åergo a reazrangement to G), l-or example, neithe:: I 2 ( ZB)' nor Z-cnLoro-Ð t 6- "J-1íphenyif-ura:: çZl)' rJ-ð'íphen)¡ithicinen (29) mass d-iphenylp;,razine ùcw a signifrca::-, ¡:caj< ^t úS 165 in their . 5{a- ò iJVV Ua 4ô ¿Q H -e .+ CH: CH # CH- CH (u) H lv -----+> tl H + H H I + 4TI-) .ê ---> H H H cHg a) EEqå. N H5 cgHs U H H É. q E Ê tr J N ¡¡ 0 ci c 5 (27) (zs) (2e) -"t9- It is essentlal that Ì;he cornplex skel eial- rearrangement.s urder- gone by oxazoles on electron Ímpact be fui-ly inves-i,1gaied, botlt tc i-llcrease the useful-ness of nass specirometry in the iC-entificaii on of oxazoles anö., more i:nporta:rtlye to increase our unrLersianding of the skeietdl- rearraf,'l.genent processes .¡,hich are possible on eleciron impaci" the s¡rmbols used. thro,.rugÌrout the d.iscussion are those ad-opied. by Bud.zikiervícz, Djer,assie eüÌå lYj-Ui ur*J7 from i::itial- propcsals by a() Shar¡3ono"t An the texi, ihe proposed. fragnentation processes of caiions are índ.icated- by arroivs VV ) (heterolytic cleavage, i-wo-electron si:i-fi) ' '¡,-hei'eas ihe proposed. fragmentations of rad'ical caiions are depicted. by hal-f arrows (ft, ) (non:oiytic cl-eavage, one-eiectron shifi)" The :oresence of z r,etas-r,abl-e ion for a fragrneniation is shcnvn by a:i asterisk (") eiì:er i:l ihe iext or ín the fi-gures, anA the letiez's h"r. are used to ind-ieate tirat tÌre compositions of the ions in a pea-k have been estab- lished. by high resolution measurenen'ts" -20- RE SJJ-¡TS ¡¡ID DISCUSSÏON Those mess spectra which are record.ed- gz'aphical-ly (¡ig. 4-2te) are in a foid--out forrnai a.nd. are loca'r,ed at the end- of this chapter j:: (píZ - p6B) " Those mass spectra which are not tepresented. graphic forrnr{' are recorùed. in the Table ccntai¡.ed. in append-ix 't " the conpo- siiions of ions deter:ri-ined by higþ-resoluti-on measurements are iisted- i:r append-ix 2" 4?) lìôsr k¡ ^ entation ìicde s of Oxazoles In their prirna:¡r fraginentatlon on electron i:npaci, oxazoles resernble fura:as, rather tha.^r pyrroles or pyrid-ines, i:: ihat their l-oss is I'i4O or lf4iIO than I,f-IiCN-r1 ¿¡d. tiris suggesis initiaJ- ,70 "uth"r ihat i¡:itia-l cl-eavage of the mol ecuiar ion is directed- by the or.'rgen atom ¡'ather -r,han the niirogen atom" The mass snectra of the isomeric compor:nd.s J¡ri-d.i:nei;hy1o:cazole (31 ,ltg" t+) , zr5-ai-"nethyioxazoLe (Jo, p:-g. 5) , æe 2ri+-d.imethyioxazole /,.4o 3Z¡r sho,v characterisiic d.ifferences, ',vhich may be related. to their growrd- state structures. this sho'¡l-d. be contz'asted to the very sJ-'ni-Iar specira of the isoneric *yL.n a¡cL of the ethyimethylbenz".t"uTi "72 []ì peaks greater iinan J)( oí the base peak (laq6) are z'eco:ried. / lVhen a spectrrxr is not ô.escribed. 'cy rr=ference to a specifi c Figr:-re e +,'r\ert it is recoråed in ap,renC.íx 1" -21- cHg CH NI N N \ ù CH CH 2 0 H. CHa o o (:o¡ 3t¡ Gz) the spectra of (lo) ær¿ (lt) shovr peaks at g/e82 1t',rcn"r) ' tg5¡" (ifæärCO), a.r-ld- tSA3 @;drO, h"r") , ùL of rvhich are insignifica¡ri; i¡ ryectru-rn of (SZ), suggesting that al-methyt group is necessary for the production of these ions. À major peak at úg68 (ltCtiO") in the spec- irr¡n of (tz¡, is of much l-ess significance in ihe spectra of (JO) arlc. 3l), j¡¡åicatingi,inat C-5 of the oxazole ring is involved. in the l"l-CdO" fr.aginentatíono A sj:nrlar observation for the peak at tg 7O (l"r-UCX) It" 70 is more intense in the spectr.rm. of (3i) than i:r thcse of (lO) at\d þ2) ] suggests that C-2 of trne oxazole ring ls involved- r¡r the ivi-IÌClT f ragmeni a*r, ion " cHa cHg cHg UH H .) D 0 3 0 \)) ) \))a) -22- The spectra of 2r;r5-1:v-vnetnyloxazole (33, Fig" 6) an¿ of 'che label-l-eå derivativ e 2-d,-rnethyl--[r!-d.imeihyLo: hydrogens of Ì;he 2-nethyl sulos-r,ituent j:r the M-CHO" fragnnentaiiol:" Qs H5 N (zr) n = ¡t R. CiI, /-/\ at 6¡) = \)ol Ì(^ = u2"5^ coHs R \2 !) R=n-C H 0 (¡e) n )! =r'4rr11 , The fragmeniaiions .,'lnich ha.¡e been ascribeå to specific netþi substiiuer,.ts (see for exa,':rpIe Fígs. L,-6) are of C.iagnos-,'ic va-l-ue for ai-i the oxzzoLes exa::iined. Tne spectrtn of a J-rnetby! oxazole a-lways and a.lso a pe'ak d¿e tc tne acety]- ezåibiis a tiuT,r" peak, "t ú9 4J õz -ooth j_n of oxazoies cation (CA_COI't of rvhich a:re rninor the specira lacicing ihis substi'cuent. Simrlarly tl're spectrum of a J-þenyl- oxazoies aiways shovs a peak ui úg1O5 ¿ue io tne benzoy¡ cation (C,5CO+¡" lire d.iagnostic va-lue of tl:is pea,c @/g 1Ø) is li:niteC. by the obser'¡atioir that the 2-phenyl- oxazoles (48,49' 59) also shcrv substantial- peaks at ilS lO5 in thej:e spectra (see Figs " 16, 17). the 1f-HCl{ fragrneniation r'¡Ìrich occurs in the spectru.n (n:-:g" 22) of (21) :-s a:tered' io I¿í-RCN in the spectz.a (Figs, 20, 21) of -uhe 2-ùWL-L'.,!-d-iphenyicxazoles (i>+A)" This resuft ind.:-cates that ioss of RCN fron the rnoiecular ion speciíi- cc,iy Ínvclües the 2-substituent, æd probabiy c-2 or tlte oxazole ri:rg" It is inier.esiing to noie that the M--RCIí fraginent¿iion alr,va¡rs pfcceecs v¡i th charge retsntion to the oxygen containing fragrneni" This is + ion (ú. 1O5') in ihe evidenceo. by the com,cleie absence of a CjI-Nt2 specira of (52, 63, a_nd. 64) , al_though the spectra or all 4-phenyi oxazofes sho'¡ strong pea-tcs d-ue to this ion. vl1Ll jia n-C CH ' 6l-i1 N C C ll g n-CgHi H3 cHg c n-C6H13 o 0 \t+) \t) ) \.,OJ The specì;r.a (F:-gs " 7-9) of '¿he tì:ree isoneric d-i.me-uhyl-n-hexyl- oxazoLes (Sl"-16) shor'¡ that the node of Í':agneniaiion of the n-he>:yl cbzj;n is t¡Larkeclìy aependent upon i|s p:sition of attaclnent to ihe oxazol-e ring" The fragrnentation of the siö-e-chai.n is very siniia¡ for those compound-s (ZOÕ+) with the n-hexyl chai-n at C-2 (see Figs. 2 arìd 7). In particular, the pea-lcs prod.uced. by þcieavage (ús 96 ir:Tig" 2 utd ús 1'f O in I'ig" 7) are m'¿ch smaf-Ier tha.r those arising by þcleavage lu-ith hyd-ncgen rearrarrgement to 'r,he oxazoLe fragment (úS 97 ín Fig. 2 anå' y/s 111 in Fig. J). À sjmil-ar situation (i.e, B-cteavage v¡ith hyC.rogen reâ-rangeinent rnore pronounced. tha:r s::np1e þcleavage) is observed- j:r tÌre spectn:rn (lig" 8) of the /¡-n-hexyì- isomez' (:S) , al-,.hough the simpte p-cleavage process is nore pronouncea (tS 11O 5ï, of g/e 1i1) iha:r i:r Figs. 2 æñ, J" Thiis'oehavior:r should. be contrasied with ihat exhibi-r,eô in the spectnxn (¡le" g) of the !-i:-hexyl .o"tpourta (56) " Frorn trig" 9 it ca¡r 'pe seen tha'c B-cJ-eavage prod-uces the base peak of the spectru'n (!/g 1|t0) vrÌrereas the corresÐonô-ì:rg process wiih hyclragen rearran:gernent j-s cornparison (gle 111 is 27Á 11C). ninor in "f tS r.J aHl r-C4H 9 ^ t\ N \ cHg c i-CaHS CHS o CHs i-CaH9 CH¡ 3t) (;a¡ \t9 ) The sj-i.e-cha-in fragmen;;er.tj-cn obsel-ved j:: the spectra oî 2-i- butyl-!-nethyloxazofe (40) a¡.d. -uhe iso¡neric d.i:rethyl-r-butylo:iazoles ß-l-lg) is aral-ogous to ihat in the spectra of ihe corresponö.ing n-he:t¡'l- oxàzoles (20) anô. (3446) " the spectra of all tne i-buì;y1 oxazoles jl-+C) show a greater rel-ative aþrnd.a:rce of j-ons due io simpl-e $' cleavage of -"he allqfl chain ilean d-o the spectra of the correspond-irrg n-he:ryI iscrne;.s, this may be accounted- for by tne greater stabiJ-ity of the second-a:y rad.ical produced by þcleavage of ihe i--ouiyl gz'oup, over the primary rad.ica-t -res',:lting from þcJ-eavage of a n-hexyl groupo An exa;.ri:ration of i;he spectra (see Fig" 21) oi'the 2-ùWL-t+'5- d.iphenytoxazoles (ff-f}) sho¡,vs that the þcieavage rviih hyd.r'ogen rear.rarlgenen¡ occ-.rrs, provid-ed. the ufkyl chain conta-ins three or more ca.rbon atoinso In the case of 2-etlry\-\,!-d-iphenyioxazoLe (56rTíg" ZA) such a,process (þcieavage v¡iih hyd.rogen rearrengernent) ca:-u'rot oÐerate. Alihough B-cieavage of an ethyi group is norma-lly a favcurabl-e Þrocess I e"g, the ì,i-15 :.or' (g/e 1JB) is ihe base pea,¡< in ihe spectrum of 5- ethyi-4-pher,y\oxazote (5t') ] tne lvr-1! peak (g/e Ð+) jrr ihe s¡æctr.r.rn of $6) onJ-y has a¡r abwid-a:rce of 3% Gee Fig" 20) o À rnajor fraginent ion @/. ZOö in the spectcum (l:-g" ZO) is fo¡rned írorn the molecul-a-i' ion (úS ZStl) by ioss of a¡r acetyl ra,licaJ- in a concerted. pz'ccess (meta- s¡able ion at úS l7OÕ). Such a fragmentation v¡ouJ-d,. require extensive TeartaÍ\ge¡nent of 'che molecular ion, a;rd- lvhj-le a one-step process is not r/ excluded-, the sequential- loss of CO æa Cäj viould- seeln more ¡l-ausibie")c Ií'-i,he ¡¡.ssmpi;ions a-re rna,le that (1) the produci;s of -che $- cleavage reactions arise pred-om-l na:ri1y f'r'om ihe rro-ìec',rlar -ions i:r one-siei; T:ocesles æ¿. (Z) fur-cher c.ecornposÍ-cion reactlon" of ihese prcd-ucis "he occ-'¿i at si:¡,ilar rates > íher, the raiio= [l,t-C-;tn lþrl *,a [lt-C-li, ,)A,i, in .(, TÀBÏ,8 1" te rates of ê qlt ro ï'e raeni i:l the s¡ecì;ra or ( zo) a:rd- (zt,-z Substi-tution Pattern ltn-c,rn.n)A' lv-crnro)A,t !-methyl-Z-n-nexyl ( ZO) 'l .c 5.5 ¿7 trtr la r! -iime thy-, -2-n-inexyi ( r+) t Ò-) 2,5 -ô.xnethyi-4-n-h exyL (35) t,4"3 .Z t: 2 ì+-dine thyl1þ -n-he x-JL (.J5) 10"0 Lc t ierrns of relative peal< heigþts, will give approxinately the reiaiive rates of the þcleavage prccesses :n (ZO) arø (t+-56) " The rel-evant values are l-isted. j-rr labl-e 'î. The corresponC.ing ratios ltl-C¡1.r7/iit ana for the i-buiyl ccmpounC.s (Sl-l*C) are given i-n Tab:-.e 2. -[],i-c,nr)Al t c" q1ÀitT.? LJvut Loo Ap'rroxinate raies of 3:c.'eava-qe and þcleavage v¡ith 1fy4ryåe-!--iq4rr-24,ge,- ( ment in the spectrz of zt-¡,o\ c Substitution Pattei'n r", ^ -= ' A, i¡,1æ_H-lÁt l-t\-4Jf7./t¡L . ) 6,, !-rnethyl-Z-i-bu1;yl- ( 40) D1 o") L.,j 4)n ethyT-2-:-:c*yi ( 17) -7 -7 2'1 /,j -ð.rnetny!-L-í-'cuiyl ( J S) tet )ol 44 4 ¿ 2 rt -Ã)methyi--! -i-butyl ( I 9) I _27_ From the vafues ín Table 1 it is evideni that the rate of si-'nple oxazoles (ZO) a (¡+) iha¡r þcl eavage is much less in the 2-n-hexyl "t j:r the L,- and 5-isomers (J5) orå (16) o this behavioi;r paral-lels that obserwed. fo¡ the isomeric ethyl-pyrid.i-nes, vrhere it is obse:ved' that ilne.LV.-u-E-.- -- ^-- I aorl l-s of iorq abundance j:: the si;ectnm of 2'etnyLp¡rriôi::e, t 74 but constitutes the,. base. peak1, of-! the spectrun ofI J-ethylpy¡'id-i:ren2 ^+ì-'."ì--r--:À ,. ^ CH; CH3 cHg N + CH ? cHa çHs c cHs N CH¡ U cHi 0 o G) G) (Ð G) . the obselvecl varíations in the rates of þfission corresporrr- to (f) a:to d-estabil-isation of ihe ion þ) vd-tli respect to the ions k) " the calcuJateô el-ectron åensities fot oxzzofe (talfe 5) pred-ict thai C-2 is the. posiiion of l-cn'¡est el-ectron d-ensity, ."/nich j-nd-icaies thai (-Ð r"y be tire least siable of the three carboniun ions þ, !, 8). À sj¡úl-ar argurnent has been used to rationa-l-ise the obserr,'ed fragmen- tati-on of the ethyl pJ,ridinesoT5 ÎÌ:e ca-l-cu-l-ated- ï-electron density in tlre p;rrid.ine ring (faofe J) is greatest ai C-3", iinevefore tlie ion (¡) shoul-c be n-,ore st¿rble thra-r'r -r,he correspondrog ca:rbonir-Ln ions at C-2 or C-l;" The val-ues in lable 2 teîLect tÌle greater ease of þsc'ission oÍ 'ghe i*bu-cyi- gï'clìp, preswnabì-y oue to ihe ¡nore stable seconC.ary taÌ-ical procir-Lced :n this z'eaction" ltihereas there is a terfold. òií'íerence .ç7 (f i ttrj-s is in ihe rates of þfission f or ',he n-hexyJ- oxazoles alte ) ' hafved for the i-butyi oxazoles (falte Z) " Conparlson of sj¡rilarly compound." (ZO) rvltfr (r'g) ana (56) witn (Jg)] orientated. [".g. "fouu.y" sho¡rs increase i¡, ihe rate of þcl-eavage over þcieavage vriih ,an hyd.z'ogen rea-rrangeinent, for ari i-butyl glroup compa:ced to a n-hexyl groupo MADTî Z L.|\J)þ.tt ) c 'in B+ C ai-cul-ated fl--electrcn d-ensit ies oxazoie and e Corniro'.:rd. Posiiion 2 + 4 .ç. vLaL9LWn-.^ -^'l ô 0"84 I ø ¿-,) o.g7 1"O3 Pyrid-ine 0.8t noà o"82 o" rc5 Fra.grnenì,aiion of a !-n-hery-l group by þcieavage with hyclrogen rearrar-rgernent proceeC,s at a rate sj-niilar io 'uhat observedr for the ana-lo- gous creavage i-n n-bu-'u¡-Iben".n76 or 2-n-'cen';yLfvrrn'77 r\ s;gniÍica::i rate eruranòenent is obser"v-ei. i,,'hen the alkyl chain i-s substiiuied- on C-2, arrd fo¡ the [-n-hexyloxazole the reaction i-s very favou:'able althougþ the rates for tne cleavage of tÌ:e 4-rso-buiyl- ar:d" 2-iso-buiyl groups are appï.o>:irnaie'l¡r equal-" I;r vievv of tne io¡¡ abu::,.C-a:rce of the ;oeak ai yiS gZ (þcleavage rvr'ch-hyCrogen Tearrarlgenrent) corcoa:ced- to the peair at úS U (þc:-eavage) in ihe spectrurn of 2-n-pentyJ-íuran" ii is reasoirabie -2q- to postr-rlate that tÌ-re prevalence of the fragmentation d-ue to þcl.eavage .,vith hyC.rog,en rearrangernent i¡ the spectra of 2- ancl [-a-i-þ'I oxazoies ís d-ue to some pariicì pation by the ring r:-itrogen. Iransfer of a f- hydrogen to the rÉt:.ogen aiom via a sj-x-¡nenbered ì;ransition state G o" j) is a pl-auslble explanaiion, al-thougþ this has not as yet been veri- 'l fied. by 'uhe appropriate d.euterj-un abeiiing. I + R H R H N ) U 0 ('f) \r¿l In concrast to the spectra of the 4- a'''6. 9-a1lqi1 oxazoles (15, 36' )ót )g)-^\ Ì/tpc.t1 snov¡ iittie side clla-in fragmeniation, other tha.n þcleavage, the spectra of ',ne 2-alWL oxzzoLes (20, 3+r 37, +O) shov peaJrs due to Y- a¡C" ò*f ission cf the allryl sid.e chain (Aig' 7) ' this behavicr¡r is in agreercent tv;th ti:e geireralJ-y unfavou-z'abie natu:'e oí þcleavzge of an alþr] group at C-2 of the oxazole rl-ngo L-\//ñC v¡a rl^ ¡J cHg j+J N N N ù cHg CHr CH. '.-C¿l-iq \-Hr''J o -C,'rlc4JJ 0 J1 c ^ /r:\ \.¿{- l ,J Á27 \tL,) l -3o- -i The -r,hree is cune ric C.ì:ne thyJ--ú-buiy-loxaz ol-e s ( U -l-l) eflrib i (with one exception) nonnai- fragrnentat¡ot p"o."sses upon electror¡ inpact. The specti'a of al-l compouncls shovr najor peaks X tg 1lS (lvf- Ci1-,"), j:: absence of deuierium iabe-ll-ing, it is not possibie )" bui the to d.etern::-ne rvhat proporLíon of this fragrneni @/e :tJB) arlses by loss of a methyl radical- fr-om ihe t-butyl group, a:rc1 r,-rhat nroportion by a- cJ-eavage of ihe !-netÌ¡yt groupc lhe abur:¡â-ânces of ihe I{-CHJ' icns in the spectra (Figs. t+-6, 15-i7) of other i-neti:yJ- oxazol-es (3O, ii , 33, t+6, +8 j 50) are al'u¡ays less tnæ Z5% of the base pea-k" It is therefore probabre that ihe major proportion of g/e 1i8 in -r,rre spectra of (4i) (¿uZ) originates by loss of a methyl raCica-l- fz'om the t-br-ityl groupo "nA 0n the basis of the observed fragnentations of l-ineihyl, 5-i-buiyl, arrd l-n-hexyi oxazoles" we wouJ-d- expect the spectrr¡n of the 5-i;-butyl oxazol-e GÐ to have rnajor peaks X úS 106 (u-cfeavage of the t-buiyl group) and. at úSl J8 (þcl-eavage of the i-butyl group)u }Io'r-¿ever, these are cnJ-y n-inor pea-hs in 'che specir-*n of (13), the rnajor fragrnentation being (ø-cleavage hyd-rogen rearrall.gement trne oxzzole) which Il4,li.Lö vriih tc '1O7) produces tne base ;oeak of the qpect-r'un (E/e , CH: N N CHg ..'rì LJt5 c2tt50 rì OHS C2H5o 0 H3 0 uv2v2¡^ $g) (60) \o ¡ / 7,1 The !-etho>çroxazoles (r9, 60) shovr no tendenc.y to cleave 0 ¡o the þ-snbs-,,ituent, and both compound.s shor sj-n-ilar eljmi¡rations t !iz" M- C2liL4O4O. The base peaks of both spectra lof (f 91 60)] o" fornied- by cleavage the arÈ-'1 with ihe charge being retained by of 2r3- "5-bonC-s, -rhe ox¡rgenateð. fragmento The spectrum of (6t) al.so shov¡s peaks resul- ting fron three successive l-osses of 28 na-ss i¡:rj-ts fron the molecul-ar íor:.o In ad.d-j-iion, there is a su'ostantia-l- peak at úS 96 due to s- cleavage of tÌ:e J-ea.rboethoxy group (UCr$Or) " csHs vb¡ I þ Ubí'1 c N N \ D D n ) 0 Br (¿-¿.") ('+¡) $z¡ lhe eiectron-irnpact j-nclucea fragmeniations of 2-phenyloxzzo\e (62) and. [-p]ren¡'1cx-azol-e (¿,4, -lig" 10) a.re very si:nila-r'" the çecira of both ccnpowrds coniain the noiecuJ-as 5-on as ^Þase Peakr ani. shq',n¡ sequentia-l eli-mination of CO aricl tlCN to give a peak at t39A" this ion (tS9O) (Scirene tiren loses a hyd.rogen aton to give úS 89 '6) " The spectr'" (lig. 1t) oll 5-ð.n-L.-phenyloxazo1e (Uu") arå- 2-d,,-l+- phenyioxazole (44b) are d-ifferent, pro'.'ring ikrat ìàe hydrcgens on ihe oxezo13 ri-eg ar"e preC.crninartiy not ra:rcloriised- on eleciron :-rpact" the j-s spectr-,n of (14¡) sho¡,zs that almcst all- of the C.euierir:n (gl'lù 2^ Ucl-iulw r N + "g'7' \ U U (62) (¡¿) + ci. -L lo U-Jl-/t rç.c), g/g 9o (") ts eg SClfllltl 6" invoived in -uhe process lrl4O-ÐCN, whiJ-e the correspond.irg -orocess irr the spectru:ln (44a) is li4O-ECl{" the peak is nroved- to gle of "i úS 90 )i in 'the spectrrxn (¡+") , but is r¡raf-tered. i:r tha-ü of (¿¿¡) [lig= " 1O r11:. Tne ion a-, gle 91 (¿4") fragments further bJt }oss of eiiher a hyô.rogen or a C.euteriun aLúcmt e-s evinced. by ihe partiaì- shf-,, of 'ükre peù. zt g/e 89 in tne spectz-ur cf (r¿¡) 'ro úS 9C i-n thai of (¿¿") . these results a-z'e consisicni v¡-ìth a fragmeniation paihvray lor (¡+") involv-r-ng rnigra- d-euteriu¡l at C-i 'co e¡ ther C-l¡- or 'co the l¡-pheriyl tion of the "fug' f oll-or';ed. by ioss of CO arrd. HCi[ i;o grve Q<) " T]re iorl. k then loses either z hyri:ogeî or a åeuieriu:it atorn a¡rd. may be ¡'epresented, at least in part, -ünfori;unateay, by 'cY:e b;cJrcLíc ion (i:') " the regi-o. úg 89 - úg 9l 2Z in the spectrum of (44a) is too cornpJ-ex to enable a cal-culation to be nade for the relative loss of hyd.rogen ant d-eutei'ium from g/e )1" + T ñ¡Ðr H H G') G') the replacenient of ihe c-! hyd-rogen 5n (4r¡) vri'Lh brcninø, does not greaiì-y change the fragmen'Latj-on patterc' 'Ihe specirt rn (f ig. t Z) of 5-bromo-L-phenyLoxazoLe (52) shcnvs seqüen'tiâ-l ehmination of CO a-:rd- IÌCN from ihe moiecufar ion io give tg 168/170, rvhich then loses Bru to give a peak at dS 89" This fra.gmenta-i,ion is consistent v'¡ith migraiion of Br fyom C-! to C-1,. i¡ the molecuiar ion of (>Z) , fol-lov¡ed- by loss of co e,ol HCÌ{ to gir" Q.") ldS168/1JO], which loses Bro to gre g/e B). ¡ ^ L.l- cs H coHs f\l ¡.\r r CH. cH2D o \.fl^ D o J 0 (),r) \4ta) (rr; Thre spectrun (¡:-e" li) of 2-raethyl--[-phenyJ-oxazcle (tþ) ha-s been a;raiysea r"¡rth the aid of higþ r'esolution measurrements (falte :'), anå ihe 2t spectra (fiig. t4) of the labelled. d.erivatives 5-d., -2-metb'yl-l¡--phenyl- (l5A) oxazoLe (A¡ ") a-nd 2-41 -rne'thyl-[-phenyloxazote " #TABLE 2r" (liy." 'î C orrpo si 'ci.ons of' ab.;:rdant í'rar¿irent i-ons in thc snectrum l) of Loxa.zoLe. fon Rel . Ab. Cornposition Fc-rnal /. \ (ús) (,Ð (fr."r. ) C.erivation" À. 2.t trô C^H^N iri-CO ¿)l 99 -. *,n c i3a 37 tfdn :;i 104 cf6N (6(iÐ \ia jlro c¿tu Gol") ¡,1{O-i{Cl{ 1a3 7 tf5* or%) I'f4-TI.0)4 "Ft $ît l,{4i{0'-HCII 9c c4r l,t404IIJCN AU " 89 59 "l\ },f-CO4}T.,Cì[-H) The ion at g/.e ¡J1 in *,he spectrr-rar of (L5) is for¡ned bi' loss of CO -írcrn the molecular ion, a¡rd ihe furti:er loss of a hyi.rogen atom ('cc A/e ij}) d.oes not involve the hyd-rogen at C'5 ias etzicienced- by ihe af-most conplete shft ot úS 13A in tìig. 1j to g/e 1J1 in Fig" 1¡., af'cer correc1:cn f,or a smaJ-l- a.nou¿:t of d-o contaminalt]' +5- The concerieC. loss of Crä{O from ìlee ¡nol-ecular ion of (4!) [meta- stable ior' at tS 68 ] to give the ion t7lc4 [falfe L, cgsg' h'r"] requires that tne rnethyl alrà phenyl groups eiiher become atiached' to ihe salne carbon atom, or to each other. this is azr exa'trple of a fa3.tLy j¡r general reafraïrgement in $eenylnethyL oxazoles, artd. is d-iscussed- ín Fig" 1J 1s fonned.' a]:nosi more de'r,ail bel-ow. The peak "t tg1O3 exciusively by l-oss of CrHUO from the molecular ion (falte 4) a¡rd- is una_ltered" j¡r the spectra of (Þa, à5b). T6is peak coresponC.s to ionised. benzonitr:-fe Q), formed. by cleavage of the 2t3- znd 4rl-bonôs" J cs Hs ' -e [c'6t ¡-cil I tf 0 H3 +o Q) , g/e 1aJ (tø) an the spectrr¡¡'r of (+5) is moved a-lmosi The peak "t tS 90 entirely to g/s 91 j¡r i;he spectn::r of (45a), but is urr'altered' in tlie spectr.rn of (¿¡¡) þig=. 13, 1l+)" This behavio",:r is si¡ailar to thaï; observeC. for (44a) ana (¡44), anC- is consistent v¡ith migration of ihe C-5 C.euteri-un of (m") to C-4, i-o1l-ov,¡eC" by ì-oss of C0 ar,C. CHrCi( i;o grve (l|, The ioss of either a hyd.rogen or a d.euter:i-um aiorä fz'on lc- 89 j¡ the specirwo of (4J) io acco'unts for the par:Liai shifting "f úS (l'igs" 13111+) sLroril :lJZ 9O in i:he spectx-urn of (W")" these spectra ihai ti:.ere is no randorn-isation of hyd-rogens on the oxazol-e rirrg rvith the hyd-rogens of either a phenyl or a methyl substituerrt" As tkre spectra (figs. 15, 16, 18) of !-metiryJ--l¡-phen¡'lotazole (+6), þ-methyl-!-phenyloxazole (+Z), ar'd- !-me^,hy1-2-phenyloxazole (40) are different, bo-r,h fron each other and frorir that of (|5); it is rur- likeIy that their fragmentations may be explai.:eed. by the forrnation of a comnon rnolecuLar ion. cÊHs CH N N N \ \ a^L.tÉ c H,s ar coHs CH 2 0 (,16) (¿¿) (ha) CH¡ N cHs o c^H q. o b (+6") (n") (+6-+8) d"t shov¡ peaks 1JO (IÍ-CIíO')" the The spectrz of "t tS (¡-6) (+Z) are quarrtitativeJ-y appropri-ate ions in the specira oe ""¿ rrovea to g/s 1Ji j¡i those of (46a) arra (47a), inC.icating that the hyorogen at C-2 is noi j:lrol-ved. in this fragmentation. the qpectra of G6), (tl), ana (48) [lig"" 15,16, 18j ai-so sho'w a peak ai g/e 1ata" peak d.ue to C#g fra.gment, vhe¡'eas In Figs. 1l aû, 16 ttri.s is eniirely " in Fig" 18e it is due onJ-y to a Cf5N species. -11- The deconpositions of (¿þ6) ar-'ù (k7) afso occur bJ' ¡upture of (c"f' 1O3 ir-E:.g. ^tJ) this ilrc 2r3- arß.4r5-bonds fo¡rnation "f tS " fragrnentation 'oroduces the peak at tS IOJ (h.r., tlSn , 3Ø! of g19 1Ø) i-n the spectrum (F:-g. t5) of (a,6) , but simiiar cleavage tt (lZ) gives (yæH,CN, retention on oxygenated- fragnent) ivhich ihen ¿-n/e 118 ) charge decornposes by loss of CO to 9/e 90. peak in the spectrr¡n of (47) is quar:.titatively The "t úS 90 moved to g/g' )1 in the spectr.rm of (+7a) o 'Ihis obse-rvation is consis- terr,c v,¡j-th 2-5 m:grztion of hyd.rogen itt (,¡',2), although the spectra (trig" 1i) oî (44a) ana (441) show no evidence of such a transfe;'. A possibJ-e explanation for this behaviour may involve the íni-tial- oinning of a:: oxzzoLe on electron ìrnpact being ôependent upon the suOstitution of the ring, It is possible to drav.¡ &ifferen'c forrns @, tt, 9) of the oxazole rad-icaJ- cation for 2-, l+-., a1.ld 5-phenyl oxazoles, each rvith the cation s'ca-büised. by being in a benzyl-ic positiono If nrigration proceed-s to a, carbomurn ion cen'cre , 2-5 rnigration v¡ould. be more favoured îov a 2- ar j-phenyl substituent @, Q than for a l¡-phenyl subsiituent þ). R coHs + Àl N t\ \ T + H R R 0 LI R 0 6 à 0 6', '5 (c G) þ) -38- 41 Skeletal P.earran,qernent P rocesse s Invoivinq B ro¡qi:ie Iligration. cloes not Replaceinent o-f tyle C-5 hyd-rogen "f Q+r) v¡j-th bronj¡:re greaily cì:a:ige ihe rnass spectral fragmentation patte:rt. 'Ihe sÐectrlnÌ rnajor ç-r.ig" f :) of 5-br.omo-2-nethyl-[-phen¡rioxazote (jJ'; shows ori-y two d.econposition paihvlays, lvl4o-Ci{zOi'i-Br' to grve úC 89e aIxl ll40Ær" to gtue {g fiO (a1i el,j¡rinations are subsia:rtiaieC. by appropriate meia- siabt,e rons). these obse¡vations are consis-beni wiih migraiion of the broinine atom to C-þ either prior to, or concurrent lvith" the expuj-sion OI UJ" The behaviour of (52) ar\A (rJ) upon electron impaci is sirn-iaar; in both spectr.a a rearrangerrrent of the 5-bro¡dne atom to C-[ is ind-j-cated-, follo:¡¡efl by Ìoss of o>q¡gen and nitrogen containing speci-es. A notable feature j:r the specira (Iigs" 12, 19) of (52) ar,À (51) is ihe absence of a n,i-Br'" icno This is pariicularly su:çrising as the soectra of ¿-l)' 5- meihyl oxazoles shov.' a M-Ci!' peak, and- cieavage of the carbon-bron-ine bonõ-, .,yith e>:pulsion of a brornine aton, shouLd. be an energetical-ly favsur.able process" The absence of such fragmentations i-mplíes that ihe learrangeineni of a 5-brornine to C-f is a very favourable-Ðrocess" Lt al-verna'r,ive e>:planation -ihai l,{-Br' ions are not seen because ihey both are u¡stable anå fragmen'c furiher-is uril-ikeJ-y, as the spectra of botÌ: (f¡6) a:ra (¡O) shov; l,'i-'!5 pcarks" These ions sho'.!-¿ be sj¡rj-iar -,o the i,I-Br' icns Í:.o¡n (52) arià (51) a¡i- wo',-rl-a decoinpose at about the sa::ie rate" in carfuTast v,r-th tire spect ru ot (rZ) ,ta (ii) , thaL of [-brono- 22ç2Ãip1-,eryJ-oxazole (54) is d-evoid of bro¡nine coniaining fragnent íons. The fac-;le loss of a brcmine rad.ical confirms tÌre e:cpected. ease of el-imj:ration of ih.is species, a¡d. rnafces even more reinarl Tire mol-ecul-ar ion cf (5b) loses brornjrre arrd carbon monoxiCre i¡ arr apparently concerted process Ii."" I,[-(CO + 3r"), rnetastable pea]. at tS123"5 - 1ZZ.O) to give {e 192. Such a fragmentaLion vrould require extensive reaJrargemeni of the ¡colecular ion, ancl .¡¡irjJ-e ihis ca:trot be e>:clud-ed., sequential- loss of CO a:rd- Br" vroul-d. seem more cred-i'ole. 1"\ S kel-et ai- iìe arra-i'rgernen'r; Proce sses Invoivlrg Phen:¡l or lteth.r¡I Grour: Ì'iia-cation. . One of the most in'ceresting features of the spectra so fa¡ ð.iscussed, is the ma::ked- ted-ency for marry oxazoles io el-i¡oinate eitile:: CO or CI'.O" frorn their no]-ecu]-ar ions" The abur:.c.allces of the 1,4-28 and- I\,I-29 peaks in tÌre spectra of severa-i oxazoles are lis'ced- i-r-i Tab-re !" From tirese values (1"¡fe 5) ii ca:r be seen thai for atr a1lq¡l oxazo1e fragmentaiion proceeds ihrcugþ the aìþi su'csiituent when ii contains three or rnoi:e carbon atonso ",rhen Tire aJ-jq/¡r cfla.J:r conta-ins l-ess ih:n three carbo¡r atoins 'che rnajor frag- nentations inr¡olve cleavage of ì;he ri:ig systen. If fragrneniaiion proceeås ihrougir the o:cazor e ring then, in the absence of a rnei.h-y} s:Ès;i¡uer-c, i.l-40 is always a prrvaien-u lragrnentation rJllocesso If i:re -40- vbr1^Llr rþ (zt R D (¡¡) n = cÃ.3 N ") n n4f'7 \ $s¡ R = c;t 6Z) = vb¡a^u- R (z\ i5 0 (¡e) R. = n-CrH.. R = cTIfo2 N (zz) lL-¡! (¡+) I( ÐL cgHs 0 H  - 'then ox.¿zoLe contains a metleyl substituent fragmentation proceeds by the processes M-CiiO' or M-CO ¿f" l$l) j-s the on-ly methyl oxazo]re rvhich d.oes not lose CHO" from the molecuiar ion]" (ir") (+¡¡) j¡r.ð.icate t:¡lfr, ttnen z 2- The labe]-led compound" "tf methyl group is preseni, the hyd-rogen atom involved in the M-CHO" process comes exc}¡sively from that subsiiiuent. In the absence of a Z-n-et'nyL group, ihe h¡'{¡6gen atom is lost from another subsiituent, but in no case does a hyclrogen atom attached. to the oxazole ring participate in this fragmentation" The spectra so far exa¡ni:reo ind-icate that ioss of C0 from ihe ¡noiecular ion of axazoLes al¡nos-r, certainly involves C-i of the oxazaLe ringu There is aiso eviôence , frorn. the bronninated and d-eutera-r.ed -tirat i;he cornpc.uni_s (lr¡u, 45a, 52, .5t), vrhich suggests tjee migration of t4 !ÉÐI4i, a-Trces sitions of the l,{-28 ions for 2 -d-isubsti- tuied oxazol-eso Compound" fts]. Ab. [lt-ze] Composition Rel" Ab, Compo- si'bion (7,) lut-zl)0,") (z) z3 I,140 6 }I-CHO " (zt r.Q I\440 21 .iii{ii1u ") (zz) t3 M40 2 114ÌiO' rr c (¡o) 1!ç ^ur\ 3t) U 7 l:t:yl1U 4Z (+e) 0 ¿) (+s) 0 9 j\,{4ä0" (lo¡ 0 0 $t) i,{-c0 0 (¡u) 1 l\,i40 0 9 $i) 27 li40 17 l,f4lio $e) 2 ¡{40 f+ l,I4iIO' 10 $t) l- ''f\i, 7 t. ìf --f (r a¡ ri ^ 24 20 -t.9- C-5 substituent to C-J¿, either before or d-uring loss of C0, is nand.atoq¡. this ir> ! migraiion occurs even if the 5-substituent is h¡'C.rogen (or d.eut¿riwù, e¡d- it is r.reJ-iJ of hyd.r.ogen back io C-J before erçuision of CTIO' as one ur¡it. I'fore reasonable explanations are tirai either hycirogen tra:isfers 'úo oxygen and. then CHO" is l-ost as one r:r¡-it, or ihat loss of a kyd-rogen aioln occlrrs conconitantly wiih loss of CO" The latter process rvill- furnish a cation þ) r',-hich v¡i-ll be more stabl-e than the raiical cation (q) produced. by loss of CO, The observation that the processes llÍ-CO*{' arì,1 ì!t4ä0" ofien occur together (Figs" 'ti, 15, 18) suggests ihat l-css of CO a¡:d- i{" as d.iscrete r:nits is the more probable expla¡lation" the ob- served fragmentations (nig. t4) of (45a) can be raiionalised- by the fragmentation patlivray outlj-ned. in Schene J" pr.esence an ion (CgHg, h"r.) in the spectra of The of "t ú.,1OL ihe phenyimethyl oxazoles (¡'S - 1+7, 50) demartd.s a group rnigration to .give either a species þ) [vrith both ihe phenyl and. roethyl groups bonC-ed. to the same car.bon atom] or a speci.es þ) [vrith the r:nethl'I group atiached- 'co the phenyl rjng] " As the irLitial- trag:,enterions of -r-Jrese cornpori¡ds (LO - +1' 5A) a.¡:e slrailar to those of tire !-d-e;tero.(¡rþ"t l*5u) a.rd.5-brcmo oxazoles to C-4, (5Zr 5j), it is probable that the 5-subs-"ituent migrates "t has been postul-aied. for ihese compouriC.s. Unfess an exirenely complex Tca-rrarLgernent is pos'uuJ-ated, ihe iragr.en'caLion (ttt csH csH s cg Hs N ù € -e <-+> IJ H2 J o D 0 ut-t D CI+ D H lt+Þ e) tle ^^ E I (") l¡I j, ñ TJ r.rJì:--î-/-t v o2/LL- - u ¡l V \JL.L t_ T D /\qì I (w C.ñ-- C {:.=* o, 2 + (!), ts ßo t -DC,î''l- I 4 ('*) I 2H¿r I \r/ ,1, tE 1oJ 91 SCIIEI'G 7. CH¡ coHs C ^H-o3 N N ù u c sHs cHg CI CH: 0 ¡¡ a (+z) (rt) (rc¡ + ! c R c.H=- c-cH- 6, t ) I .ftDr' H. g./ G) of the labelled. ccnìpounds (+6^, JaJa) necessitates migration of the C-5 subsiituent to C-2'. rt has been shs,vJatT9 that the rnigratory aptitude of a trùreny1 grou! is approxirnately ten times thai of a nethyl grou-roe The rnigraij-on of' tire C-! substituent io C-/¡ shouid. t¿ren be greater tn (47) than i¡:' (+6). in agreernent wj-th',,his¡ the M4IïO" lon is four -ujrnes as abr¡rd.a:it j:: t:re specirtrm (Fig. t A) of (L7) than it j-s in the spectrrm (f ig" t5) of (46)" Iloryever, r!rc peak at tS lOJa i-s more iniense in the spectrtm (46) aïd- of (45) tÌ:an in that of (+ò " As the CUiiU ions produceå from (47) vroufd- be expected. to wrdergo further fragmentation at a similar rate, these resuÌts may meerl ihat the formation of the CtfU fraSnent invol-ves the migration of ih,e C-A substituent to C-5. Äliernate"iy, only one form of 'Uee molecrilar ion may give ri se to a CU$U fragmerrt ion" a:rå ihis fornr may be ißore prevai-ent i-ïì th€ mol-ecular ion cf (+Z) . ¡t¡sfl i-n$ 17 of either. C4a or C$ of ttre oxezoLe ri-ng in (46) or (47) r,¡ith ''C pto- vj-d-es the orly cer-lain vray to d-isti-nguish bet¡¡een these possibili'¡,ieso -t+5- presence of C#A ion in the specin¡a of (tO), but not in The " tleose of (aB) und (49) refl-ects the greaier ease of cleavage of tlne 1 n2- ånct JrJa-bonds lt'oen a 2-pirenyl- substituent is present [see for exarrple -r,lre lragmentation of b) , pÕ7)" Î,{BLE 6" Rei ative ab¿:iåa¡ce of n/e 165 ln ihe mass sp ectra of coini:ounds contahing phenyl subsiltuents. Compourd ReI"Ab. úg 16A ilvrÞa4o¡a¡aø v¡ vr¡vv (y") (JU 2 rJ.Ðíp!rcnyl-1 e 2 ¡J;-or{id. azoLe 53 J¡ r! -D iphe nyl-2-py rone r3 81 J, I¡Ð ipLenyL)4'J -ep oxY-2- 21 B1 cJrcloPentene-1 -one Di-phenylnetha¡re 2g 9¿-Qô Sti-l-bene z^ 68 !, i 0-Ð üyd. rophena¡.thre ne 3o 68 'î 4hioro-"i, 2-diphenyieih ane Õ 68 Bond- forrning reactions, r,vhìch may be si-lúlar ',o those C'iscussed dçcte, a1so occur during the eiec;ron-inpact iird.uced- fragmentation cf tlre dipher,yLat:azoLes (Zl , 22, 54-58) " This is evj-denced- by ma;or peai -*l'e (Figs" ZO - Z+)" Appropriate metas-rable peaks establish tnat g/e 16j specles are d-augirtez. ions of tg 166, '¡¡ních nay ori-ginate by a rearrafrgemeni .¡inich involves attachnent of bo'ch phenyl groups to the sane carbon atorn of the oxzzoLe ring [c.f . fonnaiion of G) ]. It is possible thai the facil-e loss of a hyd.r'ogen atom from g/e 166 is a-ssocia-ùea vrith 'r,l:e formation of the fl-uorenyl caticn (-d ldT165J from the fluorene ra-d-ica-l Lon (ry/e 166) ,. d"though ior. e*-u"nsive re- arra¡gement to give the phenal-enium cation (!) ca.rueot be excl¡dedn f + (Ò' ls t65 6) , g/9 t65 observed- in the mass The forvrra-bion of an iot: "t úS 165 lnas been spec-ura of a m.xnber cf compound.s (tlote 6) rvhere its presence C.ernards a phenyl migra'uion. An exa¡oinaiion of the intensity of this ireak in the spectra of a mrnber of ci.iphenyl heielocyclic ompound's (talfe 7) shs¡rs that -ilee presence of a prono',:ncec p"* åt g/e 16J is no'c characierisiic oÍ e'ìiher a CipÌreryi substriuted. heterocyclic systen, or of the CnÏlr- C4J)5F.-, noiety. It appears tha'Û tn" Clfg fragrnent is genera]-ì-;r corjj-neå to the mass soectra of !-rnein'oe:'ed heterocyc-ì Íc systens containing -¡ T,\BLE 7" R.elaär,'e abundarice of m/e 165 fragnents in the nass spectra of d.iphenyl substituteC. he-i;e rocr,¡cf e s / Þ al Cornpound. -¿t-Ð C oi¡rnound Re] . Ab, 1 m/" I -/"X o, n/e t65 \/o ) -@) Ir!-Diphenylcxazoie Þ 2 rl¡Ð iph.e ny;--t'n7 azo)-e 4 2À!!e thyL4.", -rJiphe ny1- oc i-phenyl- s o: 2-nler:tyl--4,5-d-iphenyi- 73 I,J-Dtphenyl-furarr 3 oxazo\e 2ì+t5-Triphenylo:cazole B0 i Jvie ihyi- I, J Ãíphenya- 2 pyrrole 2t5-Dtnhenyioxazoie 53 I,JÐíphenyiihiophen 7 [-B rono-2 ri -d-ipì:enyl o: 4r5'liphenylinid.azol-e 42 2rJ-Díphenylthiophen 2 2-i-Prcp¡rL-iari4ipl¡en¡rl- 26 24ln; o r o -J, 6 -<.iphe nyI- 2 irrriô.azol-e pyrazl-ne - a ^. . 2s!+g5-Triphenyiìrnid.azol-e 100 J, 6 -Ð iphe nyJ-p¡rcadi zine 0 ÌaoJ-Dip\aenylthia-zoie $ r Ail conpound-s j-n labl-e J, oiÌler ihan the oxazoles, are fou:là a- !, rvr o v I c -L8- j-rr compound.s (fa&fe 6) isolated instances other d-ipùreny} " It has been shormr previously that hyclrogens on â¡. aromatic ring 1- tenC. -u,o becone equivalent upon efeciron irnpact ,o) utò. it has been ob- se:¡red- in ceriai¡ cases (see a'oove) that hycLrogens aiiached- to the oxezoLe nucieus do not ra:id.o¡nise prior to fragmentation. This situation has teen apparent ihrougþout the coll-rse of this stud-y, a:rd. consequentlyt althougþ labell-cd. benz,ene rings i-nitially have tire deuierium in specifi-c pos'itions, electron irnpaci j-nC-uceC. fragmenta.tions i¡rvolving l-oss of d.euie\iu,n arrô,/or hyd-rogen frorn the labell-ed- benzene rings occurs in the ratio J : Z (D : H) [ignori-ng possible isoiope effects]. Ð t\l \ R ,/ c sHs C- D oJHr 0 (zt¡ iì = cn$ (zt ") D D (ztr) R - D In the spectrum (Fig. 22) of Ç,!-cì.iphenyloxazole (Z:o) tne ion g/e 165 is for:red- by t',ro T)at:t,*,$ays viz" (l) U-Co-SCX-ti' anô" (Z) :'t-(CO+itOl{)-il" (a:t processes are sul¡sia::tiateð. by approoriate rneta- siabie io::s)" these pr3cesses are rnodified- rn the specira of â11 q- -r, 2-substituied- Jar!-d.iþhenyloxazoles to 1Í-CO-R.C\ï-ï{" alid- },.{-(CO+P.C,l''i)-II". the spectra (Figs. 22r 23) of the Label-l-ed compor:rds (21a., Zltc) sholr tha-i; the tl,vo phenyl ri+g" are involveC. j:r the fo-rnation of k) , *a that the d.euierium at C-2 is specifi-c:l'ly lost d.uring ihe rearange- rnent processo This latter observaiion rægates the earlier mechanisiìc proposal for tne for:nation of the peak at tS 16, in i;he spectrrm of lar!-C.iphenyloxazol- e (Zl) y as this r,ech*i"oJ1 i¡rvokes ihe par-bici-pati-on of the hyC.rrcgen at C-2 in the tra¡.sfo::natl-ono In view of the p-revi ously observed- m-igration of bromj:r¡e ar,ol C.euterium atons fron C-l to either C-f or to a ia-phenyl substiiueni (A:-gs 11 19) a:rd because of the lcnor',rn ease of phenyÌ mi-gra- " , 12' 14, ' 78,79 rr-on, i-ï as proba:ble that 'r,he forma.tion of G) j:: the spectz-Lm of (Zl) invol-ves migration of the l-phenyl subsiitueni to a carboniu¡r ion centre ai C-t;, rvith concondtänt l-oss of CO to give the ion þr) ' Thi s ion ca:-r ihen fragmeni by loss of HGN a¡id- Iio tc gl-te þ) , or its re- a-rranged for::r þ) [Sctreme B]. TÌris mecha:rism d.oes nct d.rrecily invcive the second lrctero-eiom, arid- it is possible that a rneckra-nis¡n sjmil-ar to tha'i lmown to operate for -ul:e formation of þ) in 'Lhe spectru-'n o'i 4r5- rt (21) diphenyiin'i d,azole"" a-lso acco',::-rts for the f or:nation of G) f rcn " lhe foznaiíon of g/e 165 @rlng, h"r") in the spectrtün of 2r5- ô-'phenyl-oxzzoLe (ZZ) has 'oeen noi;ed. previousiy, anâ a ;necharism irroposeè íor its î.-,,u-uíon"31 lron -,.he speci ra (Ttg" 21,,'¡ of (zz) a:rd. i-us ,l¡- ,Jhat, C-eute-¡'a-ue¿ isc:ner (ZZ") it ca.r be seen i-ne hyC.rogen at C-4 is -r ost -5o- c csHs csHs\* oHs t\ N ------>-e €------Þ \ /E \ Csil 0 csH Q+ c5ir5^ o (z¡) L 40 +ê (.6%) c -N=C}I --.->/+ì ¡ H Uù ' n/e 1e3 H + ( *') + + ç¡ ' gr9 t65 (ù, 9/s t's5 SCIIEJ{Ð B" curing the forrnation of ihe C,,rH, species, but apart fron the fact thai phenyl raigraiion must occur, these resu.l-is d.o not ai--io,"r ari unequivocaì- nrecharis¡n to be proposed.. Ii shor,l-d. be noted- iha'r, ihe pea-t< at tZ l1f .. 74 s¡ec-t"u¡r,' ' of azole (23) is or:-ly tn" ¡u.=" i:r the Zr\<üphenyiox ,f" ", peak, which Ìneaiis f,hat 2r5-míqration occ-ü-rs ¡nore ¡eaiíLy tnan 2)a- núgrationu -51- À possibie fragnentation pathway io account for the fonnatioir. of {e 165 in the spectra ot (21) a:ra (ZZ) is sho'm in Scherne 9. Àl-though -chis fragraentaiion route aCec¡uately accounts for both the conceried and. trvo-step processes to tS 166 in the spectrum of (ZZ) , it can on-1y accowrt for 'rJre one-step fragmentati-on of (Zl) to g/e 166. the kinetic to ihe formation of {s 166 The use of "pp"o-h62 "x".",in" j:r the spectra of (21, 22) ga\¡e no correlation, thus proving that a j¡i coirünon mol-ecul ar ion does not prod.uce the rearrangement fragments both spectra (c,f. Schenes 8r!). N +ê __>-e (c#¡) c + 2 -ci{ + I 0 COH tr -u-i\ coHs o COHS S COH J (zz) --0 + @, ús 1'55 ¿i JI ¡tJ ( *') cg Hs N TO -e (c6n) ------à ____) 2_ + li 'ñ Ll a É H v jl J à -vtf \¿L ) SCI{E¡.,E 9 " -q9- The ¡recha:rism outl-ined- in Scheme I requires inch:sion of C-la of the cocazole ring in the icn in the spectrum of (Zl) rvhereas the ", .,n9 ' rnecharrism given i¡r Scheme ! rrequires inclusion of C-5 in tlr-is fragment , , . /_\ (tS 162) " La-oeiling of either C-[ or C-! of the oxazoJ.e r-ing in (21) t1o-'C '¡-ith proviôes the onJ-y nethod. for d.i stingu-i-shing betr¡¡een the clo 4Z posslbiJ-itieso S:-'ci-Iarty, 'tC labeli-ing of either C-2 or C-5 of (ZZ) provid.es the onJ-y method. of d.ifferentiating betv¡een mi-gration oî rlne C-2 suJcsii'cueni; to C-! (Scheme 9) , arrC. migration of the C-l suOstituent to C-2" Labelling stud.ies to d-ifferentiate bebr¡een these possibiJ-ities are r-n-ó, progresso has been that ihe 2-phenyi group oî 2l+,5-triphenyl- rt "¡or*Í6 i.nid-azole- (65)/.-\ i-s. not involved iri the for:na-r,ion of the peak at y/e t65 in the spectr.:n of (65), buì; because of the large peak at tS ll+ ,t' the spectrurn cf (zz), tne spectra. (¡'lg" 25) af Zt;¡5-triphenyloxazoLe (2) a:rd- iis labell-ed. d-erivative (Za) lvere examined" co Hs csHs N N c sHs 0 ^l.J- vör¡f, 0 D D (z) (2") 43- 297 irâ loÒ - c 6 ti5N0 ,Ê -H- (n) to5 F4 .8 60 -c0 (21 €) 4. 166 Ë40Ê F F: 269 20 89 1CI5 0 l_30 I oe^ 4óV ÓUU FIG" 25 úe ic0 -cgH"Ð3i{o aaìn! åe -¡{' (Ëã) EO 155 -c^H- r¿o ^ c6Hs D - ol*l () AN ceHs o D -ri rÉ J Þ ( ea. ¡ FA -co ltO '.1= t{ j ¿v ?.'12 øo ¡u5 j39 q? 0 ì i_ U a. ¿, C O m/e EI Fronn the spectrum (¡ig. Zi) of (Za) 1i can be seen that two d.is- tinci fragrnentation processes occr¡ï to give (c): (Ð the formation of (tS t66) frosr the 4- and !-phenyt groups (6Aû, a:r,à (l) foz:na- "tftg tion of -uhe d.r-fluorejne raCical- i:on (ryle 169) froin the 2- a:rrò. i-phenyl groups (+Cl!,). The lon at tS 16) may lose either a hydrogen atom to give g/s 168 or a d.euteri¡n atom to gi-ve úS 167" vÏhen the energy of the i-onisirrg electron beam is rei.uced. to 10 eV onJ-y tv¡o ions are observed. in the úS 165-170 region of -uhe spectrurn of (za) ; vJ-zo úS 166 æß' tS 169 :-r, the ::atio 2 : 3. this irnplies that -r,he fonnation of the fl-uorene raCical- ion þ) from the 2- axß.1-phenyt groups is energeticalJ-y nore favourabre than i'i;s formation froin the l+- arld l-phenyl groupso Ii is a-ssurned. that bonô fornaiion does not occur betlveen tâe 2- and. 4- phenyl gï'o'ùpse because of the lorv aburrÈ.arrce of þ) in the mass spectruin 74 ot (23) .'' c c (e)- c ('Ð c6% 5È5- - Þ Ð ti II ä çz+) R. R (z+") R H R D (25) R = H D 'ol 1ì (z+¡) LL_U-Tì - (zs") R = !, -: ñ:- fttf ^w .!L_ vlf u,rl Ð v /¿L- v:f-uf- w /v- ú, - - o, L>2 / .\ (z*") lZ+ct) -q6 - The al-mosi id.entical spectru.6S lurr=. 26r27') of stifbene (z+) a¡d. 9r"lO-c.i-nyd.rophenanthrene (25) nave a major peak at tS l6i (lt-cttr') t and- it was of interest to deter:nine v,-hether or not ihe fornation of úg 165 Ln the spectra of the hyårocarbons (z+, f>) parallels j-ts for- mation in ì;he fragmentation oí' tine oxazoles (21 ' 22, 2)" îha meå-rsiable peat< (n',*) for the--'" '''I44.ií." -"3 process in the spectra (24) (25) occtirs 151 æd ihe peak shape is id.entical- of and "t tS "5, j¡r each spectn-rin, Thi s netastable peal< is broa-d, islicating that considera'ol-e ki:retic energy is released- d.uring the elj¡ri:r"tÍon'60 T,ABLE B. o îire ratlosr n/e n,6r/m'" arò, m/e i6OÁnå'íor tlre 1,i4li, process j:r the ( ¿rra (25) spectra or z+) " I or-l:_s1ng Strrbene (24) ! ,1 0-D i-"ryC.r'ophena::ihrene Po'ro ("V) (2r) c/ 4 Its t65!^* lús- t}of/n'r /o ¡ bt l/"." l-ts l\al/n+ % ¡o, tot 259 /þÕ J5 ,t,4 go8 ¿l nrO .10 269 /oy )+ ¿4Q 954 2¿ 7 2:) co4 910 12 )t) LÖO ¿v Zr.à 11iA )o) 15!p 9t, n) 40 t+zo t ))v LJa 19zc 22"5 J \ra.iues + 1t)7;, cóH5-. C6l-{5:^ CóH5.^ __.-D ^,,D ^¿H -LóHS H"o-,,t'tce us H-"(2¿e)-ìCóUs D- tz¿¡l or. l0 ¿Y, 10a 15 !t (M+) ¡¿t vi I r so(tr+) tor( n+ ) -c{ I !6t ,t !q 0 0 0 ilt t: ú: {t FlG.28 FIG.29 \nI CA I cf,t-lq_ .H c6H5: ^ ^'ll t-r- or, d) -CóD5 o5) ìz¿.,-JOo Q 5e) ?5 ec 15 sv. lo 6v 10 ov. ?5 sv F*) ¡¡o (¡+ ) 8l(!+ ) lrrtr+) e0 (*) 60 ú xI0 e xì0 40 xl0 I 165 t6l "i 20 tt 0 0 o o læ {v {v út {: {z Frc.5l Ftc,27 tlù.52 -57- The va-¡¡es obtaj¡ed- for the d-aughier/netastab-'e a¡rd parent/ netastable ratj-os for ihe process tS IBO -> úS 16Z tn the spectra of (2L) ,rrd (2r) are listed- in Tabl-e 8, the d-aughter/rc,etastabl-e raiios correlate'lvell in both spectra, but ihe parent/metzsi-able raiios d.o not" ther:efore, i:r boih spectra, gle 16j is a:'ising frorn the sa:ne inte:'- ++ , / . o\ lleûrare (rr ) o No siructure is proposed. for ihis ion (,1'"), but fron labelIing studíes (see be!-oø) it is urlikely that ;t corresponds to eitlrer the u:rr.earranged. stilbene or ) rîOdíhyd.rcphenarr.ihrene raCica-l ions. The ratio ot WS 180W", errd the abrimd-ances of tS 165 in .,:ne + tr^ro spectra e-re i-ri.d-icative of a greater proportion of ion À' i¡i the molecu-l-ar j-on of (Zlr) , ihan in the molecular lon oî (Ð) . In ori.er tc siuc.y ihe d,ecornpositíons of (Zt+) anå ( 25) fu;*tnet, the labelled stifbenes (24a - 4d) and. the labelled- dihyd.rophenanthrene (Z¡") rreï.e preÐa:red, ¿:'rd -,,heir partia-i spectra an'e shos¡n inFigs. 28'12" . TÀBLE 2o , tr n o Ccmparison of obselved- e-nd- ca-l-culated ratios for ihe l-l¡+t" ;'t!ú)!. I reaks an ine ira of ) (zt'a) anå (252), r¡ 1Q evo H"] Coinpo';:rd [lr - , [l,i -c"] 0bèeri¡ecL Ca]-culated- C,,-Stiibene (24") 1O"5 : 1 ¿ ) ôr-Stilbene (Z-þ) -l. t 5 ¡ i 1 ^. - \ 2 ,lj I o?->ir) cene \z+3) ) 3 7 t c1=) -S-"ilbene ( Zi,-o) ¿ 4 dræ rrryd-ro,chena:r-th r ene. ( Z5 u) LL 2 1 -i8- (Figs" of (2L) (n) shor"'the A'c lO eV, the srectra 26" 27) ^t* eiimjrratj-ons Ii-H"-Ho and. l,,f-C;i.", while at i 0 eV the corl'espond-ing pro- CeSSeS âI3 jri-:-¡-' --" a¡¿ ]í-CFi,"o The spectra of the iãbel-l-ed- derivaiives ) (Z+a - Z¿ua, a-nf e5a) at 10 el.f ¡ show loss of both hydrogen (tr,t-H") a¡d. C-euierir¡r^ (m+') atoms to the r.elative extents shov;n in labl-e 9" Conpa-rison of the observed- ratiose ¡,vith ihose cafculateà for ccrnpJ-ete1-y i.arr.d-om loss of I{" a:r-ld D", sirons that at i0 eV cornplete re¡rdomisa.tion of the hyd.roger^s i:r the rnoiecuJ-ar ion of sijlbene occ'.lrs prior io ihle loss of a hycircgen atom" In contrast, the val-ues lisieC, jrr labÌe B shov¡ that coinplete rand-omisation of hyOrogen does not occilr for 911O-i.iJeyd-ro- phenan,;hren" (25), rvhich rinexpecieCly ioses noie hyC.rogen than deutez'iun" These r:esults rnust mee-i.t tha'c there are ai ieast tu¡o forms of the 9rn'O- d-iÌgrcì,z.ophenantnrene rnol-ecular iono The hyd.rogen atom on one of ihese J í'onis (4") rnust con-o'letely randcni.ise (see Taofe-îO) as ihis species gives (r,/e n,65\ \Te a''e not able to íomru-l-aie a rise to the iri-3li-"j ion \r- " reasonable struciure fcr the oiher fomr( s) of the molecui-ar ion, vrhich rnus'u lose nore hydrogen than deuterium" Îl:e el i:ninatlon of a niethyl ra-i.ical fron ihe stil-bene a¡rð- ) tiO- åihyorophena-nthrene mol-ecular ions is a ccinplex processo Trrespeciive of the nature of the ion lr.od-ucing the cl-fg f;'agnen-L, ivo hyclrogen / atorns nus'; rnigrate to a cai'bon ,,,,.nich aj-reaC.y bears one hydrogen atonrr f A basic assr¡:iption in ihis d.iscussion is ihat, j:: the absence of a::y evid.ence to';he conira:ry, t\e ì'ti-1 ! fragment j:r these speci::a co-'ïesÐcï:is t o lcss cf a:: in-tac¡ ::-ethyl laiical (:',-Cno'), u-ttà tnei t:ag:.eni;¿.tions such as 1l-C1.2'-í--f a cro not cccuro 49- Î]JliE 10" Cornlari son of -r,he observeô and- ca-l-culateCL ratios fcr the l-oss of f¡a- ì o-nr,-1 l¡À OH D,- \ stilb-^nes ar,cl d.i-nyd-rophenalthlele " +l \J'-ll-rr! 0bserved Cai-cul-ated- Ccrnpormd- an3 -cH2D .q/fijJ .CÐ .n3 4Ii[) -clÐ -{Ð 2 7 2 ) '-E ôtr (z+^) 75 ?5 I-) ¿J lt4 (zuv) ç1 33 ¡¡ Ãr, +1 à r? 7 (z+.,\ lL) )I 17 LJ+ 12"5 o"5 nQ 4ç, 7a (ua) 26 31 zn t) ¡o 4( ") )¿- 4"5 79 q (zt") 2J )6 ö )l 22 2 ard- either one or. üwo C4 bonl cleavages v¡ill be necessary to el-irninate a meinyl raCical" the raiio= (corrected. for i"otope peaks) for losses of ú,1r', t cfÐ,""e and- cÐ-" (vrhere appropriate) in the slrectra of (zl*a) - "np" (Z.A¡ àrà (25a) a:.e iisted- i:r lable 10" These ratios are compåreô .rith those calcul-aied. for the appropriate losses assuni:ing corçlete rarrdon-isa- tion of hyd-rogen a¡,å d-eute rium ( see appen,:ix l-) , but maling no assumlr-- iicns as to .,'u-hrch carbon ato¡n is lost i-ir the methyl radical" fÌre vaJ-ues ii-sted. in Table 10 shcv¡'uLrat rarld.ornisatj-on of h5'd¡e^s'n a:ld, ôeuteriirr rnust occur i:r the mol-ecula¡ ions oi the stilbenes prior to l-oss of a rcr:rY:yi-raCicaJ-, othenvise the vafu.es obiaincd- for the io*tol*U= -6a- (Z*^, 2./t'o) ,,vith deu'terium on ihe cieÍínic l-in-Ìl coulC. not be corlsistertt rrith those obtained- for the ring o-eute:'aied. ccmpo'.¡nC.s (2o., 2l'.ð.) " I'c is al so noiiceable thai 'Lkrere is a consisieni ireni- io the C.evia'bion betri'een ',he observed ancr ce-lculateå va-l-ues :-n Table 10" Thj-s d-eViai;ion j-ncreases in rnagnitud-e as the deuteriun ccntent of the inolec'df-e increâseso The observeå trenC. is consisteni lyith tile l-css of CD,'beJ::g) favorred over CII-.. values :-n lable incLicate ihai ¡he ôeuterit¡rn'so- loss of ) -4.s'ti:e 9 iope effect for C-È./C-D bonå cleavage is approximai;ely 'i "0, ar,r1 as ihe seconcì-ary lsotope eífeci for C-C bord cleavage i s smal-J-" a possible eniranced cDTo is that ihe s¡na-llei'ôeutez'fu¡n expianaiion for ihe loss of ) atoin ca¡ mi-grate preferenì;ia-lIy io carbon" Tf this s'¿eric, or tz'a:rsfer, eîfecz does occur then it shoul-c. be greater for' 'lhe secoi'¡d. transfer tnan for 'cl:e fírsto The -r,heoreticaf- d-istributions for this ¡ood-el .,"¡ere cai-- cui atecj usi:tg a conoii;i-ona1 probabj-J-ity nethoC" '¡-i-uh vaj-ues of the iransfer coeffj-ci-ents fron O.5 to 2"0 (see eppendix 5-). The c-istribu- iions obia.i:red by this raethod- l¡/ere not close tc ihe obselveô. values, ar:å in pa-rticuiar did not shcrw the sa:re trend.s as the observed d-isiribu- ti-onso It rvo'¿l-d. ih';s appear ihat a:: e>qpl-anation of the observeô. resul-is by a prefereniial- 'bransfer of d.eu'ceriu:l over hyaz'ogen in a ærnpietely ra:icì-oniseo nol-ecuf ar ion is not vaiid-' l[ever'-uheiess, the conch'sion .-hat -i:er.e -is sone selection fzctc:t f'avour"ing cÌeuteriu.n i:i the l-css of CjL. ¡/z .,\ í'rar;i L::e oeu¡erated. compou:d-s appeer:s inescapabie, aithougþ \ / '-,/ vc have no-i been acie to descrlbe thls facicr n-le.ihenaij-ca-l-l-J;" -61- It is not ircssible to attempi to match observed anC- calcul-aied. values for the loss of CtI--Dr= ..r bY assuming -unat a percentage of tiie ri \ r--L.i fragneniations arise f¡'om the unra:rdornised. molecul-ar ion, as this forplies knoril-ed.ge of r',hich atoms are lnvo1ved. j:r the fragmentationo Iven if ihe ca::bon atcra(s) Iosi 'were iC.entified. yy13C label-lir:g, ii is not va-l-id- to â-qs'Ltme 'uliat an r-n:randor¡ised molecul-ar ion is necessæily arl unrearrarrged one, a:rd- hence the hyclrogen/deuieri-,:m d.isiribution ca-r'l¡.ot be considereð. io be tire same as thai i¡ the unionised- mol-eculeo 100 r(n g 80 (¡r, T E 60 rro. r fl f H.o 20 0 úz roo (l.') Ìi 80 cx¡ I ato) e ãoo FIO.6 I 4¡ 5 d40 20 {z ¡¡) lll( lt , 80 t) 5 FI0.6 LO 5 úz tz tlt E 80 2 I ¡.ì Ê 60 I tr0. ,l> s H í0 rat lra.t 0 4s I cË! ì( ( t: t á E ll0 AI FIO.8 ts f (x x¡l t!¿ taa ilil(r') 0 o lt lcr0 Q80 á (¡6 b60 ) PIO. eE ã40 lll 20 21 si tl¡ rlll(x.) Itz !6¡ 0 úz o\I _È-t ç o Io 6 ¡ßl¡lrvE ÂBû!ÐÀrcE (l) ¡ElÁlrvE ÂBTJÍDÂÍG (f) ¡rt¡lrYB ¡BUXD¡rCB (f) ô o _t c -îôl \:zt l3 i$ ir t. -{ "Y\? -+ REL¡lIVE (f) o 7 is -t ù ?l cY _or- -,âì t t¡r llt', Ë r0 I - Cr llllo v &'l*t Ë5 + ß+, at (.r tl0. ¡l: t ts 5A d rot {t Crl¡r (,\" P l.lò , r¡0tt.) ra0 l t'¡ (at.l -i'( tf' R z 50 Ê t¡0. ¡.H t0 -H'HÉt s ts a0 fE t¡t r0l l9 20 0a o {t {s coHi. ( arat ¡00 r5r tx'l .",Æ t5 o(ta't (aa ) e â f r I'F, É 60 E 60 ttq. t0a ¡68 H I H ao d t0 ta¡ 0 r¡¡ o\I o\ I I I c 0 o { rEI^lrvE l8urD^rcE (l) Er^lrvB À8ûf,D.XCt (f) E¡¡t¡vt r"BUrDl¡c8 (f) 8 ,I 3 ¡s ,-z lt I I I t ¡ aEl^lrYE ÀBUÀÐ^¡æ (f) ô olX D Y' I 2 ¡{ lo * t + 0 0? t3 lo ot aF ãrz .oIl (+ ït ¡tr 09 t0l I ¿a gra ( ¿É t 00t HrJ tf 0 I 0t ¡|l 0t H F ãot .01¡ 00 Ë I I rH)rtr I (rtt ¡l¡ aar ¿aa (. , 0¿t ,tl Iu a0t 0t B 101 Í6r .or/ É IE (rt t aa -Lg- Ir¡ ft ã 5 át¡ .ou g á I 3 lt g ,,\7._,,(rrl ( -¡.lrlt (D¡I I (-xlrt Lra '' (oy.hrl ¡- \o íF o a¡ 0? oE 3t .ou 00 I 0¡t I S aa I - ñrÁll t) 1¡d o 0t ¡l 0' F .ott ñ 3t, È E s ( l:l E a a tit c S I -L tl¡l æI (.n¡1lr 0o¡ \o)r'*"¡J( \trtl -89- C) rt ,Ë fll N) G -by- NUüLE.AR Ir,LAGI{ETIC RES0NAT-'IC,E SPECTRA 0F OXAZOI,ES. 2"1 Tntrod-uction" Nuclear magnetic resonance (n"m.r.) stud-ies of hetero-aromatic systenls2'96-e9 have shovrn that the chenlca-l shjfis associ-ated. vrith protons on, or ad-jacent to the rfug, are strongly d.epend.ent upon the position of the protons relative to the hetero-atom(s). this is a con- sequence of ihe poJ-arisation of the ñ-el-ectrons by the hetero-abom(s). i{ence it is possible to d.ete::rnine the position of substiiuents relative to the netero-atcm( s) i:r hetero-arorcatic ompound.s and to gain sorne in-fornatiol as to the. degree and. d-irection of polarisation of ti:e rr- electron system by the use of rlom.r. spectrosc opy"got91 lne latter application, when applied. to hetero-aromatics v¡ith a si-ngie hétero-atom, is of no great significarice, sj:rce the sa¡ce inforrna- tion ca:e r:suaìiy be ôerived- by the use of o'ul:er tech¡riques" rÌ¡iih structures involvi-ng tr-o or nore ring hetero-atoms ihe esti-nation of net polarisätion of the rf-el-ectron systen froro first principles is not no-rmajfl possible, ar:.C. nernor. specirometry may often be used either to calcul-ate parameiers v¿hich depend.. upon ihe TT-eLectron ôistributi-on, or to provid.e a usefu.L check on the sarne para-Ineters d-erived. by other r"*""90 si:nple exa::rpie of the Lztte'c is prorrJ-C.ed. by pyrrole -{ "ppfi""tion " theore¡icai caJ-cu-l-ations for pyrroa"3 t7n' pred.ict that the rT'-electron d.ensity will 'oe greatest about the nitrogen atorn. This nol-arisation of ihe ff-systern siiould- cause the a-hyd-rogens to be deshíe1d.ec. relative io the þhyd.rogens in ihe rrslrÌ"ro spectnln, and- this is i:r fact obser.r"d."86 -70- ôô Simila-r d.eshielùing of the C-protons in the nom.r. spectra of furan" ard tff-opnen. ^^)c rrrd.icates that tireir fi-electrons ere poiarised in a si¡nilar ma¡rler. The n"m.r. spectrum of a molecule containirrg a polar function often exhibits cha¡ges i¡ the chemical- shift of sp'ecific resonances on goj¡g fron a non-complexing solvent (hexurre, carbon d.ísulphid-e, carbon tetrachiorid-e) to a cornplexing solvent (benzene, acetone¡"93-95 Und-er simj-l-ar circumsta:rces the n.¡n'.r. spectrr.rn of a nbn-polar molecufe shovrs insigniíicant chan g.ë"93 In the investigation of this t solvent shiftt nuch useful- informa- iion has come from the study of solvent shjfts inC.uced" by benzene i:r the spec'c¡a of aromatic alo.ehyd-es ,96t97 gnd- conformationplly rigid' keto- sïerol-cts,. 9B-100 vrhere the carbonyl group is the polar function" It has been postul-ated. on the basis of these stud.ies that the interaci;ion of the positive end of the solute dj-pole v¡ith the be¡.zene Tf-systent induces a ira¡sienì; dipole in the cornpJ-exing molecul-e r a¡,¿ thar eipoLe/ ind.uced. d.ipole interaction i-s sufficient to hold the molecules in a loose col-lision complex. The observed solvent sl:i-fts then arise from the a¡-isotropy of ihe r,veal<1y-held. benzene molecule. In support of ihis h¡rpothesis, i'i, is observeC. that in a-liphatic molecuJ-es containi-rrg a s1:igle polar substituent, there is a good corel-ation beta¡¡een iàe ob- serveC. so-I-.¡ent shifts a::d -uh.e d.ipole moments of tkre to1".tl"=.1O1 AÌthough there is consiåerabie evidence for the existence of a soluie/ e6-100 solvent complexr- l-t vras not possible, usi:rg freezing point rnethods, -71- to d-etect any cornplex formation in solutions of adanantyi halid'es in benzene, even thougþ the nom.r. spectra of these solutions shovr signi- solveni fica¡rt "hifi=.102 There is stil-t considerable d.iscussion on the important ques- tions of ihe stochiornetry of the solute/solvent j¡rieraction, arlrl ihe geornetry of -J:e collision complex. A 1 ; 1 solute/solvent compiex has been prolrcsea for several- systemtrlO3-1OB ot the basis of dilu'r'ion stucliesrlOjtlol+ a-lthougþ the accuracy of the measurements is such that the co-occurrence to some extent of 2 : 1 arrd- 1 : 2 soLute/solvent _ _ 1O+,1O9 compS-exes carrnot'oe exclud'ed." T:î ono essu¡tes a 1 z 1 complex, then its forine'tion may be consid.ered- in terrns of the d-ynan:ic equil-ibrium 1{- solute (A) + solvent (B) compiex (t,B) (r) If va is ihe cheinical sirift of a proton resone.nce at a ternpera- tr,rre 1, and u" d vo a:'e the chen-ica-l shi:Îis of thai resonâ.rlce i¡ the Dure complex erc ìn a compiex free solution respectively, i;hen the equ:iJibrium constan-u, Ko for eo,uation (1) to"y be obtained from /-\ 110 equatl-on IzJ " x-/^ r* + r / (r" a*) (z) .D "u/ ð-efined- mole fraciion of benzer'e present" A equa.is Vt-Uo h i" as the arxl õ¡lB = V"-Vo. K may then be obtaineC- fro¡a a plot of XU/A against proviC^ed. plot i-s a straigþt lineo 'In d.eriving equation (Z) \: that tiris --7r- j-t ì;o nurtber ¡no1es of benzene was assuned. ihat \, was equal the of a¿ded.o neglec-uÍng the amourrt involved in compl-ex forinationo Th-is is an j:rval-id approximation, parti-cularly at 1ow va-l-ues of b, a"d its use causes errors fu K If the nunber of moles of unccunpLexed. benzene r,vhere j-s nunlper moles of benzene h = X - (f / U*) " X=r X the of anC. X the nurnber of mol-es of solute present, is used. in eo¡:ation (2) , 5 no longer liire, ar.,¿ K then a plot of \ / Á. aga-i:rst \ i" a straight cannot be obtai¡rec. frorn the gr"ph.109 This problem may be overcome by plotting A against y" 'wÌ:ere y 1gg eo^ual-s the m¡nber of moles of benzene per mole of solute irr the soluiion. If ò arises from a 1 z 1 solute/solvent complex" then tlre cu:n¡e obtained. (J) rvilI obey equaiion " K = moles of complex / lnoLes of soiute x rnoles of benzene] (¡) arrd. gives (4) On substitution exparrsion this equation " ic= [a,/ ò-qs] / l(t-(¿ / õ¿s)) " (y - (d / ðÆ))ôl r = (n ò¿u) / [(a¿¡{) (y õ¡s - ] (+) / " ^) ?rovid-ec õ"o is 1c:cnntrn, K may then be obtaineô. for a:ry va-lue of y" ,[-tt Fror¡ thj-s value of K a:rC. rvrth ö* lciov'rrr., ihe theoreiical- cuwe for the variaii on of li ll'ith y is cal-culated. anC- compared -¡1th the exFrinentaJ- ctl.:-'¡e" Good. corelation betveen observed. a¡rd- ca-iculated. curves is eviC.ence for ihe exJ.sience of a 'l : 1 solute/solvent cotnpiexo Sj-,ni-l-ar' -73- 199 equetions nray be used. to apply this approach to other conplexi-ng ratios. Ihe evaJ-uation of ö* is a probien co¡nmon to e-11 method.s for 109-111 d.eter:n:inj¡rg ..Ko'" Previous workers have obta-ined. òU" either by extrapolation of the pJ.ot of ù* aga-i:isi T to absolute zero:1a"111 or by extrapolatíon of the graph of  against y io i¡fi:rlte d-i-i-l-.tion.109 BotÈ¿ these approaches j-r¡ro1ve exirapol-ation of experimental curvesr with resulting unceriainty in i;he result¿ It is possible to obtai¡t ò¡¡ by â mor€ exact rnethod. Equation (l) *"y be rvritten j:r the fornr 4 ¡ /K aB / l(¿-¡s) (¡-.m) l (¡) v¿here A is the initial concentraiion of soluter B is ihe j:útial con- centration of ccrnplexing solvent, and AB is the equiJibrj-r¡n concentration of cornplexo As the'equilibrium sho'¡rn irr equation (t ) is assrmred. to be fasi, v¿ represents a tj¡ne averaged- signa-lr alo. hence r,/aB = (vr-vo)/(u*-vo) = õÁ8,/^ (6) Fncrn ec¡atj-on (6) we defj¡re R = 1 - (¡eÁ) = (òre - ¿) / ö¿s e ô ô A-ÂB = R.xA Substiiuting in equation (!) and- rearra:lgirlg t/¡ t,hlrl(¿¡s-n) +l/ooJ (8) -7t+ nqr.ration (8) is a¡ implicit equaiion and. ca:r od'y be so1veC. by a¡r iterative procedure. As the va-lue of öAB is pred-i-cted to be large com- pared. ivith the variation j¡r ö, the terrn lrc / (ò¡gA) ] t"y be consid.ered constant, arrd equaiion (B) reduces to the fo:r¡ 1A (ttb) (t / ao) (g) Fron ecaation (!) a plot of 1ft againsi Àþ wil-l be a straight J-ine and- ö^- is avaj-l-aJol-e from ihe slope, thus avoiàing the extenC-ed- extra- -IIJf, polations of other r¡ethods. Once ð* i-s lc:ol'n, sribsiitution in equation (+) gives the equilibrir¡n constant (tC) , ana fron a study of the variation of K i'¡ith ¿r,emperature AH a¡d. AS for complex fo::rration are obtained in the normaf- marLr"rerc initial ,r:d-i.^ted. a pranar soJ-vent/ "trd.ies96 '97 '11' solute association in the postulated. solvent complex, lnore recent results suggested- ihai 'uhe plane of the benz,ene ring may be steepJ-y inclinedr to the ptarre of the solute molecule. It has been cLaimeollJ th^t *I- sofvent shifi resufts may be rationalised. by assuming that the d:pole axis of the solute molecule locates along the sixfold. æcis of a benzer,e molecul-e, with the posltive end of ihe d-ipoie nearest, and. the negative eno- furthest away fron ib.e solvent moleculen It must be emirhasised. thai, a-s the f orces in ihe collision ccnpl-ex axe very lreak, lvhat is d-escri'ceC. as a specifi-c orientation of tl.re sol-ve'lfu ætð. solute mol-ecuJ-es ßrù f act, the tine-averaged. resui-iant na:ry It has been suggesiedrll4 *h"t the of i.if,fereni orieniations. "" -Þ- five pararneters necessa-ÌTr to frll1y specify a solvent-soiute pai-r are ran-ely avail-able, it is neani.ngless to d.iscuss a specific orientation r,vithin the cornplex, as theoretica-l}y there are e¡. j:rfi:lite nr:-rrber of horvever, demand ordered possi'ciJ-ities. lhe observeô soivent shi-fts, .a¡r solvent/sol-ute conrple:<, a:rd- we feel ihat it ís profitable to attempt io d-efíne solvent/sol-ute geomeiry wl'rich wiJ-t afford. the obselved results, prc,vid-ed- it is rernenbered. that the proposed. geomet=y i = a. ti:ne average a:rd. has no abso]ute signifrcanceo Soivent shj-ft stud.ies based. on the assr-l"nption of a specfic"lly orieniated- solute/solvent interaciion have pro',red very 'usefu.l in 'che siud;r of ma-ny siructr:-r'a1 a¡rcl stereochemical- problems.lÇt5-1oï'11tt'115 Initr-al- i:rd.icate that five-mernbered hetero-aromatics ""por-L=11J'116t117 sho,v appreciable soivent shifis, arrd most importantlyr that in iJníezoLe a¿ / the' ',,hree ring protons are sÌriftecÌ by d,j-fferei:t ,*otïrt=o "o lrora this it is ciea;. tna1. a stud.y of sol-vent sì:ifis prod.uced. i-rt ox¿zoLes shoul-d- aicL i:r ihe assignment of resonances j¡ their rl"lll.lo s'ceciz'a" Va-l-ence-bond theoi'¡r pred-icts tnat iire d.egree of conjugati on of a phenyi subsij-tuent rviih Line oxazole ring v¡i-Li depend- marked.ly on 'ú-re posi-tion of subs'cituiion" Frorn consideration of ihe varlous v:ì ence- bor:rl structures (¡-ig. lJ) fo: ihe tirree isomeric phenyiozazoles (44, 62,56'¡ i'i; is j¡::edictec tha'¡ a l¡-i:i:renyi will si:oi' the least t æt - e 2- phenyJ- 'che greaiest, conjugaiionl,vith í'ne o-Ã.azole ring" The uovo spectra of oxazole (1)118 -.,1- se./ey'al l¡--pheny-i a:rd- !-pi:enyL oxazot-=119 have been record-eC". As expected. the conjuga'cion of ihe phenyl groups N N N <:-+ <------+ o 0 0 + + (62) (6za) (62'o) .+ o (¿¿J (¡¿Ð N N N { I oo/ (66a) (66b) !!c" 33 " resu-its in boih bathochromic a¡d. h¡perchromic shj-its, compa-r.ed r''rith tire spectrr¡n of oxazole, i4 the spectra of the phenylot-.zzoles. In 'Lhese soectra, Àrou,'. iu insensitn-e tc aÌþI substitiriion bui, as pred-icted., àerend-s or: tlie positi-on of the phenyl substitueni; j:r going fy'ars a i¡-phenyi io a !-phenyl oxazole there is a bathochr-,crnic sll:fi of 1E np jn X-----r119 mali -77- 2"2 lhe oret¡ cai C a-l-cul-ations . Self-consi-stent íietd. mofeeul-ar orbita-l ca-icri'ations are based. on 2O'12"i tlre method. of Pa:iber, Parr, md Pop1el and- were carried. ou'c váih tlre aid. of Quantr¡n Cheraisiry Prograrn Exchange (Q.C.e"n.) prograrn 72"2.122 the cartesia:l coorrlinates for phen¡rI oxazcles lvere caJ-cul-ated' by t'te 4c7 progrÐîÌ Q"C"PÆ. 9+ou') the initidr- pararneters used. j¡ the molecula-:' orbital- caiculations are lisiea in lab1e 11. taSLE '11 " Iniiiel- paraneters used i:r the molecul-ar or'Ìiital- cal-cul-ations" One centre re,oulsion Valence state Resonance 13Lr / iniegrals ionis at j-on potent ia-ì- integrals' )À À / c = 11 .15 u = ¡l.ic F^ ^ = -2"39 N = 12"34 N = 1,["12 9ao = -1"52 / u = 1o"Ò1^ ^r {f o = 3+.117 9*, = -2.a6 -rvas The value of FCX made d.epend.ent upon aiom type a::d" C-X boncL iengi'n by using the expressaon l%" (s., ,/ s*) Fc. ¿ lhe val-ue 9CC = -1"872 vras used for the bond. joining the phenyJ- anõ- o>:azole rings in the phenyl oxazol-es ard. rvas cai-cuiated- as .?^-^ Q t"t Pcä." -78- 'yhere S represents the overlap integrai. lire low val ue of FCO is in agreeinent both with the diene-trce reactions und.ergone by oxazol-es (Ctrapter J), a:rd- rvith the very Iow basicity of oxazokelzL ,rmí"n inri.icates i;hat the nitrogen t ione-pairr eiectrons are j¡rvo1ved. in the Tl-electron systen" Àlthough tire planarity of the ozazoie rirg has been estaplish.lrzS the exact ring geonetry is not lc:o"vn¡ æ1d the values used for bond. lengtns a:id- boni. arrgles (¡'ig. JJ+) were ad.apted. fron those publisìred. for 'X¡2r4-oxadieizo:eoi¿o Of necessityra constant ring geometry vras ass-r:ned for aL1 sribsiiiuted. oxazol-es" The calcu]-aied. fl-electron densities a:rd- rT-bonl orCers for oxazoLe arrC. all pheiryl oxazoies are listed i:r Tab:-e tr2" 42Ç I c)) N] t\ 109 '1 .4-B u.,aO 4 I '.io ! UO 11Oo ¿to 1"32 BorC Leng'cirs Bond. Angies (8) F i.ø." JJ+ -79- TABLE 12" C al-clùated. if-electron dens:lties a¡d- ¡T-bond- o¡Ë-ers for' oxazol es" Cornpou:rd Position rr-.Eieciron fi-Ðond. O¡rìers Density 1 x 1-2 o"28 Oxazole (1) "91 2 UoÕ/t 1-5 ^õz9oZ-) 7 1"ð 2-3 ^Qà 2t f+ o"g7 )-+ O"laJ 5 1.O3 r+-5 o"Bg 2-Phenyloxazole (62) À 104 4a o"27 2 0"85 i-5 a"21 3 t.¿o 2-i 0"81 I Z1 o"g7 o "ln3 5 1,O3 IL o.8g (44) 1 1 o.2E )a-?henyloxazole "91 2 o"83 1-:) o"23 7 u"Õo i "?5 't. o"g7 3-+ 0"t¡1 q '1"0j ). -ã uooo 5êaen7'içxazd.e (66) 4 1Õ1 l-¿ UøZQnaô 2 UoÕ4 4-^ 4"22 2 4.7 ôZ ) | 0t) o"8i -80- 1¿B ,E 12 ( Contd.") Conpo'.in:å Position lT-Eiectron lTÆond- 0rrLers Densi-ty 7t !-Phenyloxazole (66) (Contd-.) + o"g7 0.1+L 4^7 à I oV) )+-5 o.Ø 1.gx o.28 2 rL-Ð. j-¡ùrenYloxazol . (ZS) 1 2 o"7g 1-5 o"22 )2 1"34 ^Z o.7g 2t .+t. o.96 0.L1 l! 5 'tr.0& 0"86 4 .1 0"28 / rj Ð ípnenyloxazol e (ZZ) ¡ .g'l 1-2 2 U"C]U 14 o.22 à 2t õ2 rì 7ô 3 I e)4 ¿-) l+ ^ôà 3-+ 0"4L 5 I cu¿f r, -à 0.Ð ¿ 4C4 a"2g 4r!Ðiphe nyLo>:zzo:e (Zl) t 1-2 2 U" /Õ 14 o.2.2 )2 1"32 aZ o"8J 4 o"g6 Uol+t U"OZ 5 1 "O3 4:z 4 4Ò T t:::plrrcryLo>:.azoJ.e (2) ¡ tr.92 o"2l 4ç. ¿ 0"84 4"22 7 1, ;26 0"81 7l + a.g7 O"!+3 5 ''l -0J t+-i ^O^Q ør)L -Bi - Tire data i.n lable 12 shcrws that the cal-culated. bond. o¡úers for phenyl oxazoles æe in good agreeraent with those derived fron vaience- bond theory. A 2-phenyl substituent causes lcwez'ing of the calcul-aieC. 2-3 bonÀ- ord.er, a¡d- increa-ses the ca-l-cul-a'beo electron density on niirogen (reiaiive io olcazole as refei'ence) bui b.as little effect on the oiher bond. orrlers aird electron d.ensities" this is irr accord with -i,he reso- na¡ce strrrcture (6Za) being the main contribuiing fom in the valence- bond. formulation of 2-phenyl oxazoles (eig" 3¡). The main effeci of eithe:. a þ-pÌ:eny1 or a !-pìrenyI substituent on the calcuiated values is io cause a lcnvering of the )a-j bono" ord.er" the reåuction j:l' bonô order is nore marlced v¡ith a !-phenyl group, and- suggests 'uhat there are sig- nificant contributions from the valence-bonrl strr¡ctures (66a" 44a) Tr-el-ectron ðensities ano (¡.lg. JJ) " The average ve-iues calcul-ated- fo-z' ff-bonC. or,lers are given in Fig' J5" In all cases the cal-culated- electron d.ensity on ca:joon is least at C-2 and. greatest at C$ r wi-th- the d-ifference irr values betrveen C-2 ar'ö. C-i beirg much greaier tha¡t the d-ifference betrveen C-)a arñ, CJ2. The ca-icul-ated el-ectron d.ensities correlaie lvel-l tvith tJ:e obselved- che,trical reactions of oxazoÌes (Chapter )) " the 'l'f-el-ectron coniributions tó the d-ipoie mc¡nen-bs of oxazole aíd. severaf subst-ituied oxazoLes, we¡'e cd'cul-ateà r:sing a poini cÌrarge 4 t-7 acproi:inauuíoí\r''¿ and. are lisied in Tabie 'i J" The d.i-pole ¡nornent of an oxezo)-e rnay be resol-ved. :¡r-uo thiee majcr cc:nponents: pt r tÌre 'lf-eleciron contribution io the d-ipoJ-er ir.,r tÌre cornponent of the i-ipoJ-e d.ue tc -82- J^O O.Lt-Ð o"g7 N tcZQ N qot. o"Ð5 nvav4 4 ¡ c 0"82 0 4,22 0 o"2B lclI AVÏìLqGE fi_ELECTRON DEì'ISITÏES A\TER*AGE 1T-BO!{D ORDER.S ! L.1o )) e non-borCed electrons pola-ri-sation of the o-bond-s, arld. Þrrr due to .the on the hetero-atomso The contribution from ir* is usually consiåered. as par-L of u ¡ bu'i; in this case it is necessâl¡¡ to differentiaie betrreen the t'¡¡o componentse Djfferent r,vorkers have assigned. vastJ-y d.iffereni velues to these three contri-buti"rr=o1 281129 Tire inte¡'aciion of the three components of the toial- d.ipole is qui'ce complex j:¡. tbe oxazcle system, In the case of furar', Pry is sor'¡e',yhat smaJ-Ier than ¡iorarrC. al-so in the opposi-te d.irection, lvhereas for oxazole, *fiis expecied to be larger than po because of the extra pola;'ísation causeC. by the nitrogen. In aCdition, the angular reiation- shì-p between llo d *r, in oxzzoLe is noi clearo the d:ipo1-es of boih frua;r ald. oxazoie conie-in large coniribut-;ons ð.ue to *o, bui '.rhereas" in furanrthis contributron (of pJ is su-ffici-ent to cause the negative e:-d. of ihe c.lpoJ-e to r:esid-e on ihe oxygen lone-¡ei- tri28 i-n cxazol-e Q7 i;he n-itrogen a'nd. oxygen l-one-¡air moments to sone extent oppose each Fro:rr a st-üd.y of ihe microwave spectr-urn of oxazol-e, Davies a'rå _ - .129-' lviackcodt' assigned values of 1 "3Ð er,ì. 1 "í-lD to the lone-pair monents of the oxygen and- nitrogen, and. 1i¡e have used these values in o'¿r cal- cul-ations" the vafue for the totaL sigrra coniribution io the d.ipole add.iiicn of tirese lone-pair moments to ihe Ç lvas obiailed. by vector being t="d.128 o-bond. moments, the vaJ-ue" bO = O"8D od bU = Oo2&' was obtained- by vecior aC.d'ition of od the toia-l- d.ipole then ç Ë," " The resul-ts are lisied. j¡r labl-e iJ togeiher rvith the angle (measured- clockrvise) of ihe res'¿Lt¿¡rt ðipole to the 1j.ne joini::g the oxygen a.,rd nitrogen atonso The coord.i¡rate system used to descz'ibe ti:e oxazole nucleus Ls aiso given. The inagnituö.e of the cai-culated- d.j-poie for oxazoLe i-s in ex- ceilent agreement '',vi'th experimental- values ('t"icn ,"9 1"J.,-o128¡' l.rt unfor"cunateiy the erperjmental d.irection of ihe moment is no+" Ic:o¡.cno 4Z^ Tne published vafue cf 'tr uÞ')u for tne d.ipoie momeni of 2-r,ethyL-t+r5- d.iphenyioxazof-e is aJ-so j-n agreemeni v¡ith the cal-cuJ-ateå value for \r5Ãíphenyloxazcle " Îl:re smal-l d.ipol-e mo¡nent cafculated for 2-p\tenyJoxzzore (62) a.-d. -ulne Iarge vaf-ue caJ-cul-ated for i-phenyioxazoLe (66) reflect ihe irú'h,ence of the val-ence iautoners (6Za) aïrd. (66e) " TÌ:e d-ipoie ¡rcrneni d-u.e to (6Za) is som.e,¡¡i:at opÞoseo to the c'ipole for the oxazole rfug, r,-hereas *"i:.e dipole d-';e to (66a) strcngiy rein-forces th.at of ihe oxazol-e -,¡- Lr!. L!-úÐ -E+- TÀrìLE 1l " Cal-culatecl- d-ipole mornents for oxazoie a:rd- some phenvloxazoles" Ànæl a Cornpou:rå prf vJ-! ulL Coordinate* l.r o+\ Conpo- Y Courpo- 1o'cef 'System" X ]-ine lotai neirt nent Oxazoie 1 1J+i 2A60 0=0"001 0.00 "69 -1.28 -1 "10 ?-Phe-¡¡¡l - 1.93 -1 ,Ø -1 "62 1.21+ 1820 C-2=1 "2)+t 4.!¿) oxazoie la-Phenyl- 1 "7, -i.27 -i.2O 1.+2 2O1 oxazoLe j-P}renyl.- 1"58 -1 "1+0 4"73 Z"ó2 17zo i{=2'0J , O"64 OXAZOIE o 2rJ-DípnenSr}-2.31 -1"06 -2.Ø x.t¡2 165 axzzoie 2¡lp-Diphenyl- 1 c-4=1 1 oxazoLe 2.i1 -1.22 -2"2C "64 l6lro "26, "75 þrl-Diphenyl- )l 7t o oxazole 4Õ.,0)c 1"53 195 1r-i nhe¡:r'l I 44 - 1.9+ -o"87 -n, o73 ¡ c¡ ¡ flf c-!=o.oo , 1"52 oxezoJ-e Systen r:sed. for i-phenyloxazoLe i-s 0 = 0.00, C"00 C-2 = O"O, 1"32 N = 1"3O, i"6g c-L = 2"a7u o"59 C-5 = 1.2lrt -A"45 Q-o¡+-^ 2"J lducl e v^ v9uvurac 'Ihe n.mor" specirur-n of o:cazoi" (1) is d-ecepiively si:npJ-ee con- sisting of three singieis at õ7.6C¡ ò7"Q2, ar'ð- ò-1"79 pepoltÌo respec- tiveJ-y" Unåer higher resoiuiion aii these peaks are resoived. i:rio multipleis, one of v¡hich (A7.gC) shorvs much less-spliiting iha¡ the other äyoo As the coupling consta:rt for the C-¿Þ aû1 C-! hyd.rogens shouii. be greatez' iirari the coupiilg constant for either oí' ihese hyd.rogens vri-th 'cheC-2 hydrogen, the peak at ò7.60 lvas assigneC. to ihe hycL'ogen ztC-2, ard. i'rorn correlaii ons rvith other l-unsubstiiuted- oxazoles, the low fieid- pea-K ( õ7 "79) was assigned. io the hyd-ro gen at C-J " In general we fou¡lc ri irnpossible to posi-tively assign peaks in ihe nellcie specir-¿n of a¡ oxazo)-e r"rj-th. b,''ro i-C.entica-l- groups, tvi-i;hout Ì;he a-id- of specific ð.euieri-r¡n tabell-ing" In Table 11. are listeC. the chenricdr- sirift of those resonarlces r,¡hich co'¡l-¿ be unambj-gr:ously assigned - an asterist (") j::d.icates ihai the assigrrneni was maCe on-ly afie:' deuteriu,:n lâ'oe1ling. Although ihere is a tend.ency for ihe signal fi'om a given subsii- tuent (.i, C¡i-)t' to fai-l- ai hj-ghest field. f it j-s subsiituted- at C-4, a:id ai l-owest field- if r-t is su'ostituted- zt C-2, ihe:re is consid.erable va¡iaiicn in the absciu';e val-ue of tne cher.riceJ- shift of a group J-:: a given position a-:rC- care nust be exei'cised. j:: -uhe interp;eiation of chernical- sh:-f-¡ cla-r,a, llhe oþservation (falte t,l,) that the cl:emi-cal- sirifts ai 2- arrA 5- hyd.rogens íall close toge'cher (¿7"5 - ð7"ô) ærC wel-l- avay íron the resc-ilarÌce of a [-hyC-Tager:r.'nd.ice-ies -chat -une d-esh;elC-i¡g oí a hyc.rogen -86- TIßLE 1t+" Chemrcaf shífts of substituents on the cxazol-e fl-Iì.g e Comoounò Position Group õ (P"P"m") v1 ia-plre;ryloxazole ( À4) 2 -rr 7 "8¡, 5 7'80 2-nethyl-[-pher¡Ylo xazoLe (þ) 2 c-i{-) 2"1+9 5 I{4' 7 "72 | -nethyi-/*-phe nYloxazole ( 46) 2 H+ / oÞO l\1J 2,i7 5 ) 1+-me*nyL*5-phenY1 ox a z ol.e ( 47) 11 7.71 4 cH_ 2"43 !-nethyl-2-pirenYloxazole (48) 1+ H 6 "67 5 CH z Z")ö II* þ r!-d-iphe nyLoxazoLe (Zl) 2 7.83 ¿{- H* o).) 2 r5.år:pneryIoxazol e (zZ) I 2 ejÃ)nefnyloxazor e ( 30) 2 ^--r ) Ze)^2 + .ti 6 "38 E ^-:) 2.25 --7 C. /) 11 c) ¿- 4 r!-d.j-nethyicxazol e 31 ) ¿ t at /; a ar, (fi) 2 aÒ ¿-) 2 s4 15 -ir t:.et;n}-.oxe*zo-e ) a!t ( 6 2 2"21 2-nethyi-J - e thcL:Y oxazoi e O) I 4 ä 5.78 0 1,o oxygen is nuch greater than ihe ôeshield-ing of a hyd.rogen g to nitrogen, Tìris suggesis that 'c:e electron densit;¡ )n oxazoles is significa:rtiy greaier ai oxygen t};iart et, nitrogen, i-n good- agreemeni v,¡i'u:r the cal-cu-l-ateô f'I'-electron ôisi;ri-Þution (f¡ig" ¡¡) . TÌre general- niethod- used in the a-ssignment of einb-iguous rescnances j:r the spectra af oxezoles is ii-lustrated- by z'eference to the spectrua (f-ig. 56) o.i 2,Lt5-irir:reihyloxazoLe (lÐ. A noma-l lfast scanc spec- vhich uz:d-er tr-u¡n shcr,vs three singlets at õ1 "93" ò2"13, and ò2"15 " higher resoiution are aJ-l resoive,l into conpiex nui-tipleis, indicaiing long range coupli:ig betlreen ai-l- cf the rcethyi grollpsc Deuterirrn j-abelii::g (Ctrepter 1) j.::rd.icates that ihe resonalce at ò2.25 is d-ue io L'oe 2-methyi grcurc, ald. the obse¡ved. splitiing of this signz1 (õ2.ö) inð.icates prefere;rtia-i coupiing of ihe 2-methyl 'r,vith one of ine other neihyJ- groupso tha'u is long range coupl-ing is being tra:lsl'nitted- prefereniiai-l-y by either oxygen or nitrogen" the remairrd-er of th.e spec-b-rr,:rn is consisierrt wi-th this reason-ing. The resonance ai òn, "9i i-s a fa-iriy rzelì- resol-veô qua:-te-u, C.ue to coupling ïfith-the a.djacent rrethyi, r'¡hil-e the resonance at ò2"13 is pocrly resoived and- very conpiex, suggesiing sign:-fica:rt coupling l',-ith both other nethyl grou;cso Às i;he ^ ccunlìng consta;rt across oxygen i-n fura:'i (Jr_^ = 1"5 co?'s")t ís greater -ube (t OoC tbaa coucJ-ing ccnsta¡rt across nitrogen i:r pyrü-i:r" r-6 = - .l <.; O.3 cop.s.) r''' \re have a,ssigned. the signai a'c õ2"ii io ii:e i-neihyi gnoup a::a rhe signal- ai õi "93 to the tr--rne'chyi gr:oup. îhis assignnent is i:r accoz'cÌ l,rlth ihe tendency (ral:-e 14-) f or a group at C-4 to cone THE n.m.r. SPECTRII|I OT 2,4,5-TRIIIETIIYLOXAZOLE (50 CYCLE SCAN) I o) P ttr 't "t¡,r,r¡þ*r,r,øi 138 c.p.s. 116 c. p. s. FIG. 36 -E9- at higþer f ield. tha¡:r a group a-u C-2 or C-5. CH R CH N CH H H 0 J 0 0 i--C i{^ (;e¡ R. i-cLH9 R i44ä9 3t) R = +9 = 3g) = D!^Û (+t) i.t. = t/4/¡IIO (+z) R = t44iÌ9 (W) R = t-cLr{g ¿+ .,/ The assi-gnment of methyl resonances i¡ ihe rloIIl.oro specira of (ll) (+l (a¡) vas made after the d-j:nethyS--butyloxazoles - 3g) "rC ) - consid.eration of both the peak shape a,rd- relaiive chemica1 shif's cf ihe inethyl signa-}s" Because long-range coupling in these compo'.:lds is much less tha¡ *, 3S), nore reliance v,ras placed. on the re-lative vaiues of ihe cnenúcaf- shjf';. In the four compounds wiih a [-meihyl group (J7, 39, l4l , 43) the methyl signa!- at higþest f ield. was assigned to the L- netlryl groupc In compowrås (JB) -"a (æ) the che¡úcai- sirifts of the nnethyt are very sirrilar, "out in the nom.r. spectra of boi:h conpor::iôs one signal- 'i s much sha:per tha¡' the oiher, and. 'bhis r,.las assigrred- to the 2-me'"hyL group, .as i-ù was considered. that the broaCening of the other slgnaJ- rvas due to long-relg,e coupling betrieen the 5-meihyl group a:rd. tne L-substituent" ån al te::native eryiaration, thai the broai- signal is i.ue to i;he 2-r,etnyl- groupe a:rd- is broa.d. beca'¿se of the o,uad-iupoìe coupiing cf t]ne ao;aceni nit-.r.-ogen rnay be d-iscor.¡nted, as several- coinpo-urids -90- r¡,riih 2- or.t¡-nethyi- groups (l.r¡ t l*7 t 5g) give shar¡r meihyl signal-s in their r14:neï'ú spectrac In the flcrrr.r" s-oectrum of a:iy d.ìne'i;hyl-oxazole each methyl signd- has a'characteristic peal< shape, so that j¡r measu;-j:rg solvent shj-ft y¡lues (talte nJ, see beJ-otv) trne eorcect soivent shift has been given to each resonance, suen if the group assignmenì; ís in erz'orc The solvent shjÍts v^rrl v^ Ì: tolt*+W --À u we"e Ot)/LL/ uttJu e'5' -op.m.)P record.ed- for the methyi and. hyd-rogen resona¡ces of a nr¡nber of oxazoLes, i-n ord-er to d.eter:line v¡hether specific solvent shfts occurred. r'¡hich couid be.of use in establishing the position of substituents. the a¡e l-isted- Table 15 resulis Ío " TAB-I,E 15" t Solvent Sh:-fts (¿ òCC ,C for sorne = I û ) oo/rrr oxazoles. Conpound- Position Group öCCt l-\ Approx:i:nate % ,H, lL oo Drpole (l) p. p PoP. "Ino lÍoment. õ4 '7 Z4 4 É.7 2 iï 7 "83 ! ø) | c.52 I 22 l'tF H 7 ")5 7 "27 0"08 I c!11 ô-rJ 4 \JiI- 1\7 L 2"27 ¿ov).^ A o2lp 1 "45 I cä_ 1 4 07 + "95 t),u'/ a17f à 2"14 I oQZ o"32 -91- T¡},LI I C ori ò^^- TJ Ap-orcxi'naie Compouncr Posi-tion Group UUIL % oolL:a p" p eIIlo pc polïlo Dipole (¡) It'Íoraent c 7'-7 )I 2 Ter:nin¿-L CH-) 0"88 0"07 t.¿Ð ATJ l¡- 1 1 o,o2 ) "97 "95 cH-) 2"13 1.5i 0"28 4 tÊ. J8 2 ^ü) 2"29 2"47 o,22 t o+) Te¡minal- CH 0,88 0"gL - 1 -0.06 à r\ú 400 vlL )? 2"1|i- . o)L o"22 naC ?o 2 Ul- ZoLt) 2,Ø o"2j 1 ) "l+5 )+ ^û loU i -0"06 5 Terrnina-l Cïl e 0"90 o"7g 0"'t1 ¿ Ð.. 1,35 1 41 2 I.¿> -u"uo 'l+5 4ÕQ 4 cif-) 1.83 4.15 2"17 1 v.¿¿ 5 ^L- ) "9, \2 Z ^ü\/I¡, ) 2"27 2"06 o"21 1"ó t L t-Bu I .¿i 477 5 t _t1_t 2.27 2"O1 Q "26 rZ ¿ CH ^=a¿o) ! 2"40 o 1.45 3 "37 \JI Õ a'7 aa7 + ^-J J.-,) L.Ll L. -) -0"0J :^ à I Ð.. G"g2 u"yö^ -0"06 -42- Î.IBI,E 1i (Contð.. ) GrouP ò^ Approximaie Compound. ?osition ò^^" \¿ * A UUI_4 0o¿L¿r Dipoie (Ð) p"pollo pe P.Ï1!" Monent. 0 14à¡ 2 iI 7.81 7 "29 "52 1.ô H 7"80 t o L/ 0.r1 CH 2"10 o"3g 1.42 \5 2 7 2"49 0"L0 5 H 7.12 7 "32 l+6 z }I 7.66 7.2+ O'1+2 I ")2 ATJ 400 EQ ) 2"57 ^ o"U+ 2"65 t;l 2 TI l"!t 7 "27 t" ul-l-) 2"4j 2"22 o,21 à '1 0"56 1"2+ 48 ^t ) 2"j6 "8 4 Ò.1 cil 2 a e I Va ! I 1 .21¡ l+9 + )2 "08 -/ 5 CII 2"28 4Ac u"4þ 1 -93- three general conclusions nay be d-r'ai,',ryr frorn the valr;es in l'able ii; 1) the nagn-i'cuC.e of the solveni shift is much greater for aryi substitu'ced oxazoles than it is for al-kyl substituted oxazoles; 2) i:r a given molecul-e a substituent a:v C-4 shorvs 'che srnaj-lest solveni effec'; r:irifi:-e-4- w, ),/r) if it is assu¡ned- that ar aiþ1 subs-tituent has iriile on 'che d-ipoic mornent of an axazoLe, then thcre is no co::rela-uion bet'¿,'een the rnagn:i'cuC.e of tl:e solvent shift a::d. the rnagnitud-e of the ca-iculated- mol-ecul ar d.ipc] e" Because of ihe ratd.crn var-Lation in 'che absol-ute vafue oí A f'or 2- a::d- !,r,rethyl substj-tuents, 'che usefrilness of solveni shfi d-ata for ùkarlo:cazoles is h¡:ited- to the iden-cj-frcation of a þ-methyi substituent" the values of  for the nethyl signe-ls of ar¡rl-oxazoles are, ho,rever, boti-r j'lrrthe;' apart a-rrd more consisteni ihal the cor:resporid.ing values fo;' .'tlyLor.?^zo.l.es, a¡ld- it is possible to use solverit shiíi values to assign neihyJ- resg?Jices i:r ti:ese co¡npounds. lire Vafues of A ío:: thie 2- at:.C 5- hydrogen sigrra,J-s in acyL substituted oxazoles a:.e too sj:niiar to al-l-cl'¡ assigr.-men'¿ of these resona-nces f ron solvent shifi vaj ues" there is a genera-l- tencr-ency [in -ùre oxazoles exarnj::ed- fta¡ie 15) ] to'c ¿ube si-gnai- due to a Có s¿-r:siituert'ù 't,o show ihe grca''l;est sol-vent shift, a-red- for the signai fron a C-lr subs'uituent io shcw a very siight olreo thus, lf solverr'c shiÍt val ues f or a:l un}-;nc¡n oxazole a-re ia-lcen in cortjttc,c¿;Lo:r riith tl:e rel ative chernicai shiÍts of the resonerlces, ald a c:í'cícaJ- eveJ-uation oí'ihe peak shapes, in its nomoro ryectnuru it is r:ossible to cie'r,errnine tj:e substitution pa-tiem of i"'rLe oxazoie rvith sonie C.egree oí ceriaintY' The obse¡vation ihat i;hose oxazoles (¿-6, 48) which have the (" sol-- l-ovresi caJ-culaied" C.ipol-e rnoinen-ts "4m , 1"U'Ð) srø'v the iargesi vent shi-fts (falfe t5) aI'gues agai-nsi ¡i^s diFole-inåuced d-ipole theory a6_1 00 of solvent/soJ-u'ce Ínteractror-")u Instead the large arr'å fairly consi sted,; solvent shifis ind-uced" by benzene in a:¡rJ- substituteå oxazoles, suggest 'uhat complex f'or:lation rnay be due toer-?f rnteraction beù¡¡een tne oxazoles and- benzene, r,'ilii-ch v¡ould be favou''ied' i'::' ary-l oxazoles because of their e>;tended- g-el-ectron syster.rso Such f'r-fl' interaction is lc'lø,rrr to cause s-;ruciuring in benz.rui'1' In an aitenpt io ciarify the nature of the sol-vent shifts i:t oxazoies, a more cLetailed- investigaiion of il:e in'reraction beü¡,'een benzene arrà oxazoles 'lvas i:ii'ciaieC-. Because cf the large sol-vent shifi (O"56 p,p.n1") shorrn by the 5- meti:¡ù groupr !-rnethyi-2-pheny'l sxazoie (48) was selecteC. as a tesi con- pouncl for furihez. st.,:d.y of sol-verrt shifis" In orCer tc deter:nine tne soI-u';e/solveni conplexing ratio, A íorihe i-rneu:yJ- of (+8) v¡as deter- niinea both as a functiort of' { (noles cf benzene/moLe of soiuie), a-nd- as a Íi::rciion of tire percent of benzene j:r ihe solvent" The ¡esults are slro,iÌr gra-ohic:lly i:r Frgs" J! and- [O' The gr".phs (ligs " 39, +O) aj.e sj::-i-l er, coi¡- being composedr essen'Lia-1i;r oí i-,,n'o stf'aìght lines of q'uite ai Ífe¡'ent siopes. The transiii on pornt -in the gz'aihs occ-drs at a val-ue a? t.îi.iL'ñ?.r\z.\.?e i:r carbon tetrach-l-or'ìde, ot JB ncies of benzere per rr-iole of (tB), lut the significas.ce of ihese va-l-ues is not unô-ersiood. lhe -95- ÊML ÈEqOü¡d Or (€), ffi! Noùc ø (a3). t? IO I6 7rõ. r ¿ no. t y( lAA ÙF !EN¡6q,/!oE OF ¡oMÈ) y (r0B or 8ENlrLqÂoG o¡ 9e) Co!..¡tr.ttú ú !.À..ø ooøtrÀt (2.2fl ) è6..dñl!ôa or !d¡.¡. .cMbd (ó.d ^ ^ ) ¡ øqô.¡!,rtle oa sollr. Êôùtut (oru ) D C.EodBtro¡ ú sólut. ooø!M! (0.u ) ffi ÈoÌrxõ 0r (¡!). ffiL Esorud Or (S) ¡2 F¡O. BEEffi (I) y (!08 o¡ Ezevror o¡ soHB) glaph of A against percerri- benzæne (Fig. ¡9) is si¡ail-ar to the pubJ-isnec ),)i^¡u'r)) 472 cuï!"es¡ 'ior a 1 z 7 solute/solvent raiio¡ a-iihougþ the other l-ine (1lig, 40) bears little resemblance to the shape of the theoreticaÌ curwe lore1:1 "o*pi"*.io9 In order io obtejn ò¡¡ by the metÌ:oC. outiined. i:: the introduction (fron, equation !) the n"m"r" ryec'cr,-rn of (a8) vras recolied- at va'r'ious concentr.ations of (49) j¡r a sta::d.arC solveni m-ixture of benrene ar'd- car.bon tetrachlorideu The resul-us for t¡¡o d.jfferent sol-ven'i; nii-Ytul€s, given a-s a piot of y aga-insi  a-re shov'm in l'igs. 37 and JB (ilnes A) , together i,rith those portions of Eg. l¡O uÌrich cover the sane values of /- - *\ y (r:r-nes ólo lr.ïom Figs" 37 æ'd JE (line e) it ca:r be seen that, i:: the solveni r:sei,., the chenicai shift of the rnethyi protons is virtuaiì-y ind.epen¿.en'u of concentrationo Tiris is unexpecied, æ j:r those systerrs 60 .,r,here ð0, has been d-eteniinedl '16't it has invariaoLy been founrL to be iarge (of the order of 15O c.poso), md fron ecluation (9) a iarge  vai_ue of õ* should- pz.ccuce a corTespond.ingly iarge value of " 1/^ (x/s) X (r/a*) +C (g) Of even greaier sig-lrií'ica:rce is the observation that aJ-ihough tne -uhey l-ines -1r a-nd- B j-n Figs. 3J etyd JB cwet a connon ra-'ige of y values, do not cover a cor:respording rüLge of À va-lues" These results incticate tltat arry excianati-on of the soiven', shif'us rvhich i:rvokes a:: equ:-l-ibriunt be-L-.'¡een corepJ-exed arrl uncorilple>:ed soiute is untenabie" If' such an ec¡rriiibri.;rn Ì:c;li.s, then equation (S) is valid, a:làron rearrangi:rgrgives -97- equaiion (10) B/L ¿,/ò¡s i:t / (t-(x'*^ / (è* -^)))l (tc) Äs boih ô.- arro Kt a-re consia¡.t the vafue of A d.epends only onB/-t' (5r), !Ð and a-s shor.n above for (43) this is not tr¿e" Because of ihe signfica:rce of these .results in ihe inierpz'e- taiion of ihermod.¡.tl.amic vafues calcuJated. for the posiuJ-ated. soLver*,/ soiuie comolexes, ihe rr.rTr.ro spectra of a nrnrber of clifferent types of ccnpowrcì.s lvere recorü.ei. ai various sol-ute concentraiions i¡ a const¿:rt benzerre/carbon teirachloride solvent ro-ixture.'Ihe relevarit values are lis-ceo i:l lable i6" lrvo :rnporLani conclusions rnay be drav¡n frorn the values in lable 162 1) in every case the position of the resonance rneasured is vir- tuajly inC,epend-ent of concentration, and. 2) the absoiute va-l-ue observed for ihe chemical- sh.ft (öOS) is alrn¡ays in'ue::meàìate bet-l,¡een / ihe chenlcal- shift i:r carbon iei ;r'ach¿orid." ( öCC:^ ) u:rd 'the che:nical -)+ shif i; in benzene ( ò^ -- ) " It vou-Ìd- appea-r ihat these obserr,'ations cani " 6rt6 orrì-y be e>:pl-a-ined by assr-:.n-i-ng'crre.- the solvent shiJ'i is nai.::Jy a pro- ?erty of 'che soiv'ent, '}'.,'o aJ-terl-ra'cive expl-a:raiions oÍ our resul-ts -'chai K in eo,uati-on /.\ (1) is so snlai-l thai rve rvcuJ-c not expect to see a-ny variation ln ò over' -a'ne conceni:caiion rai.€e siud-ied-, or' -that increasj-rrg trrc concernt'¿Íion of sol-u'ce caused- a variaticn :¡i 'c?le chericp-i- shíft equal anri oppos-; te to  - i'/-ere e):a.njneC and- rejected.* The obserrraiion of nocleraieiy iarge vai-ues ItS!]l15.-r CclnJ-rouucl }¡lol.es of sol-utc òc,FI- ò¿\B [n"r-r"."tru -] /ntc:Ies / A (nro-t,er,/.) 'benzerie Groul-r bb r\3 of ( rn) lle:i¡;Ìrcs'b Lorvest (1r"p.m) (p.p"^) l?"P* An.i,s-rolc 1 .32 o CII-. 3 o"3g O.O)+?- Gl) 2"25 "16tu t 3,68 ",29 1"60 11 o,2_1 o,o2.g CII-, 3 o,3g 0.01¡,Í2 ,?- "6tl 3"29 3 "31 ( r oc2tí c6Ir6) j.tr.'oan:i-soIe 2"?5 I o,111 3 3 o"73 t 0"1 1>N "23 "r3 "Bg "16 "bö 1 o o"o73 2*cIr3 2"O5 1 ,5O o.53 1,96 2*ìrie'thyl.'ìl etlzo -. "13 "6'/1 -0,02 qrrì:rone lJIcthy1c.ycl-o* 2,25 1.56 0"10 Z-rJIt3 o,g5 o"g-l *0.02 o"g4 0,01 hexa-nonc Ca:'vone 2"ö o"707 0"086 1--cfr3 1,9 1,8 0.0 1"8 0"0 \oI g._cH 1"8 I .I¡2 o"3B I .67 o.o3 or j I . o .>Ê 1 2.36 1 o.56 2"2 0"06 5 -Jlie tlty-l-"- 2-"phe nyJ.. Cè'J "11 0.089 5-Ðrlj3 "80 oxr,-z,o-Le (l¡B) *0,08 5"6 2"O)-y- o,063 D"4H j 2"36 1"80 o.56 2rO7 .Jf e thy1..-/1.--phenyl.* 1 1 o"52 2"57 I ,, tA9 0"58 2"38 0"09 I ,81t "2-3 5-ÐTr3 o,.razo-t.e (¡6) o,266 o 2-"crr3 2"37 2"o o,37 ZÔ¿¿ 0.0 !-t"-Ilutyt.*2 elt."^ 3.68 "o3 cli¡re tkr.)¡l oxazole (,t1-5) *.o"aj \,crl3 2"2.7 2. JO 2 "10 o"0J 5'-t*Bu o,g2 0" gB *0,06 or,9J 000 / ðOU is Lhe averagc posi-tiou of' a resonâlce A* j.s the shj.ft :ln the posÍti.on over a r¿nge O1î SOLUjIII C0i'lCEllT'RÁ'Tl-Oi\S i,n a of a reson¿ufoe :Ln going from the given benze.ne/ c,arbon te Lrachl-or id e solve nt l..eas'b to the mos'L; conccntra'bed- mixtu-t'e, so.ì.utioli in the givcn so.l-vent mixtlire " -99- for A (f*tfe t6) rncaf,'ls -tirat if K (a::.d. consequen-r,ly -,,J:e concentz'ation of ,qB) is snal-i tiren ò* nust be -farge, a:rd- hence over the conceniration renge s'curlied. [f;of" 16f a significant variation of ò si:ould. be obser'¡ed no matter v¿hat ihe vafue of K' It is al-so interesti:rg to note tìrat sr:.bstiiution oi tìre publ-i-shed valu"=îXo of K ari'cL ò-* for anisole (61), i¡ eo;ira-rion (8), inC.icates tlrat over tJre concentraiion ra::ge stuðiecl (f aofe 'i6, rwt 1) a va-l-ue of A of aI;proxiraateiy O"lp pcp.Ino siroul-d- be observedo The n.n"r. spectra of (61) i-n'oenzene measurecl o'¡er a lriðe concentration range siro;,red onl-y a srnall- cha-:rge (O"Ol* p-p"m.) i:: ihe chenical- shi-ft cf ihe r^ethoxyJ- resonelce, ind-icati:rg that ihe second- expl a:r"¿ion'is not viable. As ca:bon tetrachlc-¡"iC.e is to a snall exient a cornplexi-ng solventt the nom"re sDectrum of (61) 'v-,'as recoråed over a lriôe concei:traiion range using cyclohexai:e as solvent, the values obiained- a¡e lisied- in Tdole 17" The srnai-l- up-fi-eld- shifi i:r the r,ethoxyl resonance of anisol-e on going f-¡.om solu'cioa (,tr) to scJ-ution (5) is a-scribed to ivrcreased. mol-ecular association in the more concentrated. solutiono This up-fieicl shjf+; is greatei. than An= observed- for (67) in beiezene, or in benzene carbon te-çczc?.Jorid-e rdxture, over a compa-rab-i-e concenira-t ion ra-nge (f ;o:-e t 6) a;riL r¡,ôícates thai tl:e smal-l vaJ-ues of Ar.' obtainçù Íor the other co:ipc'".ncis (t;of e t 6) are probably d-ue to concentration effecis a-nd- not to com'nl ex f ornaticn, -1 00- flrìRÎ.1 4 7 ¡ J0 ChemicaJ- shift of the methox.¿ i'esonance of e-nisoj e i:r z Sol-ution nun'þer ¡ 2 C (moIe Q"t6 1"79 j oncentration s/titre) "a1 Chemi-cal Shifii (p"ir.n,) Z ÃO the chemical- shift observed for the inethoxyl resonance of (61) jrl cycrohexan:.e (j,66 p.p,rn") is very si¡rilar to the vaiue (3"69 p.p.rno) obtai¡ed. in ce-rbon tetrachlcrid.e ai a simil-ar concentration, and- irråi- caies tnai. îo: z)J prac-vical purposes ca-rbon ie'craciúori-de can þe taken as a non-conçlexing solvent" T¡:e ind-epend.ence of A from ihe conceniration of solute ¡neærs that ,/ 96-100 rne , sol;yarLT,/soJ-u'úe coilision compl-ext a:c the e crd-ered. soivent À^) A^^ caget. ¡Ul r¡U./-- expJ-a:rations of solvent shi-fts, both of .¡rhich invoke equäibriurn-t¡-ce reactions, becorne wrtenabie" I: evertheless, j-t is stil-l necessa-rJ¡ to expiain both the geometrically specific solvent sl:ifts .¡¡l¡ich are obser.¡eC- in the n"n"ro s¡recira or-' ¡nany conpor-ind.sJ6-1 'QR.l"ai::g oxa- zoLes, a::ct- the observ¿.iion that tl:e nåmôr. spec'i;ra of non-pol-ar noiec-uil-es õ.o not ex:rbii sol-vent shift eífecis.9i As a ¡ossi-cle expla:raticn of our resul-rus 1¡v'c a.dva.nce t*o lcst-,:l-aies: "l) fo:' a i:r a solution containing both co¡:pl-exing and. non- "oi.rr.r" -1 c1- coroplexing solvents in given pronortions, the conposition of the soivati-rrg (on shel-] aboui a sol-ute molecule is consta:rt the n.m.r" ti-ne scale) " Z) In the so'lvation of a poiar rirolecu-l-e a:r ordering (possibi-y d-ipole- i:rd-uced- d-j-potar ín naiure) of adjaceni moiec',ries of tre cora*o1ex'ing sofvent occu:rso this ord.erÍng causes the nagneiic aÎisirop¡r of ihe cornplex:ing solvenì; molecuJ-e to act (in tne time average) j:r a C-efiniie Ci-rection io ihe solute rnolecul-e" The composition of the solvating shel-l- rnay weil C.jffer f:com the composition of the solvent, and vdli d-epenð on the -natr:re of -uhe sol-ute a:rd solvent ¡noLec'.:] es" In pa:iicular, ihe d-egree of solvation of e¡: sofute by e¡ona-i:ic solvent, v¡ir-I depend- to so¡ne ectent on aronatic ^n ti:e iaagnit-¡:öe of the solutets f -systemu lnis acco-,;nts for the faci that the solven'c siti-fts in aryl oxa.zoies are iarger tha:r '¿hose in the co-rresponoíng a-lþÌ oxazoles (lalte 15) "' The acceptance of these pcstu- lates inakes the resulis i-n la'i:le 15 æò. the pifr:lisileà solvent shift resul-ts ccupai:ible, a1-ukiougþ it is emphasiseå ihai a considerabl-y more d-et¿ited- investigation of the cause of sol.¡eni shifts is necessa:¡r before a finaf expl-a-'ra'ci-o¡. cair be adv¿-'rced-" If the expl-anaiion postulated- i s basi-cal-iy cor¡ect, inen ihe usefulness of sclvent sl-lift stud-ies, aìthough resir'-¡ ctecì i¿: one vtai¡ T¡ renova-l- of the post'*lated- the-mod-¡rn:ui-ic basis, rll-i ce consiC-erabiy ex'iend-eC. by ìne doili'ty oí these st'.;d-ies -t o give ns; inío¡:lat'ion on iire solvation of organic nolccuf-es" c) tf,t ñ H LÐ iú UJ o -102- CIIEI/rrCAL REACTIONS 0F OXAZOIES" z1 )o t ïntrod-u-ctior'" Initiat stud.ies of the chemical- reactions ol oxazol es vrere Cirected. rnai:ùy towarüs the d-eter:rúnation of the siâ'oi-lity of the ri-ng systeni. Àtteniion has been focuseå on the probleins of the iniroduciion and. the mod.i-ficaij-on of substiiuents only in the past few yearsc Fron the forrnul-ation of oxazoles as azafura-ns, ii might be expected. that they woul-d be aromat:c ccrnpor:nd.s, sj¡nüar to furans but l-ess stabie srC- ¡nore basic because of the j:rclusion of the pyri-d.i:re tyi:e nitrogen. Hov,'ever, oxazoles are foirid. to be very feeble bases i tor exa-nrp1e ihe trKa of oxazol-e (1) is esti¡Taiec- to be 1O-& ijmes that of py"rd*".14 }'{ost oxazoles wj-l-l- form hyd.rochlorid.es in anhyd-rous eiher, but these sa-l-ts 47tr are ðecoirçosed- by we::.er.')) In general-, the oxazoLe ring is stable to ai-kal-j-, ard- sornewhat rnore stable to acid- hycroiys:-s than the furarr sys- teno The stabil-ity varies v'¡ith the subsiituentr ttith l-d'kpxyoxazoles / /^ - - - \ (68, R.- = aliçÈ) being reaClly hyd.rolysed by C-J.iute mineraJ- acid-s .\ za 1 z--7 /^, ;^\ tJe9i,)tr tJcnene r ul e Þ R ',*ñ N H R R O RO U RO SCHIiììIE 1C" ¿^z Tire o:cazole ring is resist >-rft io recluction.S Cata-lytic redrrc- t1on of tle oxazo1e ring nas been acirieved- usJ:rg special- cond.iti-on t 1138 but,in general, aitempted. red.uc'¿ion results in ring .L"^u^g..139 Cata- lyiic reduciion of ar¡rl oxazoles alrra¡ts results i:r reduction of the aromatic substituent 'orioi: to cleavage of ]Ú'ne oxazol-" "iog'i'B The r.esistance of ihe o>iaz,ol'e ring to ¡ed.ucì;ion is fur-ther j-l-iusira'Led- by the conversi-on, i:r gocd. yie1d.s, of niirophen¡rl oxazoles (69) to a¡nj:ro- phen"-i oxazoles (70;r1L0'1&t a¡d- of oxazoLe-\-carbozylic acid. cirlorides Ql) io oxazole-L-aj-d.ehy a." (72) .28 R R N l\ R R N O2-C 6 H4 U NHz-CoH¿ 0 (6e) (zo) ccl. cFi 0 uu2l-i N N UN Ð U R R o R 3 0 Qt) Qz) 0t) -1 04- în contrast to iis resistance io red-uction, the oxazole ring is r¡rsiable to a iarge m-rnber of oxid.ising ageat so21 Boih "¡1+1-1i+3 afrqy-l and. aryi oxazoies are cl-eaved, usudll-y ihrough the oxygen-carbon l-i:rkage" OxiC.ation of 2r1¡-di'netb,yloxazo\e (.J2) vi.-"h )15 potassitn pelTneflganate has been r"eporieti to give a iow yield. of 2-me-vb'yloxazole-la- 4t t carboxylic acid. (l:) r'"* bl-,i this is the onJ-y report of il:e successful oxid-ative moC.ificaij on of at:- oxazole suosiituen-u. Ve::'y tiit1e Ís kao,¡,'n of the cou-rse of electrophilic subsÌ;ituiion reactions j-n oxazol-es. Nitraiion of aryi subsiiiuted. oxazoie ait'rays ltio,itþ results irr tne introduction of -ûhe nitro group iirto the subsiituenti:, ilTC a ",_|!L-t A l-phenyi grouo :s ni-traied- in preference to a 2- or [-pj:enyr gro'Lrpo lliere has been no reported- niiraiion of th.e oxezoLe rtng; the fact that nitric acid- is a suíficiently strong oxidising agent io decornpose na:ry 12"1L8"1J g axazoLes- '-' *^y'oe ihe reason for l-ack of success i:i atiempteð. .^ir- lil UI 4^!-l LIUIfJ ^-^ ô The siiuation r''¡i tÌr regard. io hal-ogenation of oxazoles is less cl-ea¡. Cycl-isation of benzainidoacetophenone ( J4) vt'"n ar! excess of phos- þhorus o:tychJ-orid.e , prcC.uces 2-phenyi-5-(p-clr-1oz'ophenyi) -oxazole /-\ iA - /,-\ t T2) "'- 2Å.ieib'yi-lp-pir.enyJ-oxazcle (jaþ) j-s resista:rt to chlorination v¿i-ih r:hospirorus lrentachloi'íd-e ai 'î8oor1P brr" uråergoes brorninaiion ai roon ..1Ã^ ie;n'i¡eratu-rc to gle j-atono-2-nethyl-¡*-irnenyJ-o:cazo1 e (53),'t" S'evera-l- ,ì tr^ oi;her cxazcles uncìei'go broi:ri:ra';ion ree¡.Lly in the five posit;orL"')u 2rjÃ).phe'r,ylozzzoJe (ZZ) is re¡c-rted. to resis'ú a-l-l aitempts at ì¡::oinina- 'i5a -,iao.r--- ea u::rerr:ecteo resuii i-n vier'¡ of tire ease of niiration a:ic 4^t chl-orirration in the a:¡ri group of i-phenyl oxazcles" C,iLC0C¡Ì^li-rIo, ¿ C0 C,H-öt coHs (zÐ N B cHg N o \ $s) H¿ \-bn5 p-CL -C O 0 Ø) 151 Oxazofes resembl-e fura-irs ,152 i:r i;hat they reaclrr' *U.igrï_,r, 'i rJ-cy,cLo-aC.åiiion reactions" Oxazoies reaci wiih several- d.ienophiles, bui the ¡rost extensive study has been mai.e on the a.d.dition of mal-eic . 153 15¿+ aJìrryc-rl-o-e- a::o- naJ-erúd.ao''o Unl-ike fura:rs (76) lvirere such add-ii:-on oíien l-ea.ds tc cxo-conpo'.md.s (lò152 [s"heoe ^,11, i rJ-cycka-aid.itio;: 'co oxazoLes usu¡i"l y prcduces al'1, aromatic pyrid.j:ie O.eri-vaiive" R r. LJ_ V R X o + it it // // CH-X R [ /o, Ø) ÞUI-ri!I,!¿ i t. the t¿:c of ccrnrrou:xJ- fomed- by oyclo-a¡i-d-itlon to a¡. o:azol-e is C.eperdent on i;he sdosiitr:t'ion of ì;he cxazoJ-e, as rr¡e-rl es on ihe nature -!UD- of ihe d-ienopÌriIe" For example, add.ition of r¡a^l-ej¡aid-e to [ri-i-i:neir'yl- oxazoTe (31) gives the expected. cjnchoïìeronic acÍd- imid-e (7S) , rvhereas the sa¡ne ad.ùition -uo 2.\t5-i;rimethyl oxazole (JJ) gives 2r5r6-irtnethyl- L ( oxyli-c (7 5 4) -c arb a.rnoyl-pyrì-aine-+( J) -carb acid 9) "n'5 .--NH U ozH U l-r.Jv¡ CONH vt )? l1 2 cHs H3 3 N t\ (za) Qg) À mecnanism (Scherne 12) has been -postul-ated. í'or ihe 1 ,J-cyclc- a.d.d-ition to oxazoL.="'t55 It is suggested that add.ition of the d-ieno- phi-ie across t]ne 2r5-positions of the oxazoLe give-s the norrndl- oxo- campound (80), .,vhich undergoes cleavage of the oxygen brið-ge to form a JrL,-ð.i-b,ydr^op¡rrid-ine (Bt)" This conpoi:::d'chen laromatisesi by one or mo-r'e of fou:' possibl-e el-jmiuation pathøays, thus accor:nting for the obserrred varia-ui on in product type. There ha-s been no report of 1 involving an 'J-cycl-o-aCd-ition aryl substituted. oxazole, alìi:ough 2-plnenyl-J-eihox-yoz zzo1e (59) is reporì;e.J tc ¡¿ive a:r ?aro¡raicusr reaction rn/ith rne-leic arurùycì.rrð.a.X53 Tiie j-rni;oriance oí' the cyclo-aôd-ition -eacti on as a synthetic route to pyriC.ine d.crivativcs, othenvise ciifficuli; to obtain, is il-lustz'aied- by 4 / tire syninesis'/^-7 (Scncme 1J) of pyr:ið.ox:ine (BZ) frcn [-meth¡¡]--5- -107- t, LI X X X tt H R X 0 I I HO X Uñ CH ---+ H R À D N R N R N R (ao) (er ) _H 0 R N R lt HO _X R ß N R _____-____+> HO - l-ìR R R ¿/ R X _ XOH R R SCIE}E i 2" ,,^Õ (8li eihoxyoxazcl-e (8J) arid. frznaronitrji-e " íI LJ \.ñ \-/i¿ t\ ? cHg CN CN A t! HO CN \YH ñU H20 H u^:!-^r{ i-l- \. n (BÐ \9^ É+n IJ cHs l\ iì i.ì02 c H3 1 az\ (ez) SCTM,E 13 " -1a9- Resul-bs a.il',å liscussion. Althcugh tl:te ox¿zol-e ring is generaÌiy sieåì-e to base , oxzzol e (1), v,;hen treated l.¡ith n-butyJ- iithi'.un at -554 Îo"'10 nins, ïras col:r- pl-eieiy Crecon¡oseC." and- anal-ysis of ihe reaciion mixtr:re (\t-"P"C") shoi¡ed -r,he presence of at l-easi s1x'Eeen products' 2/a2i.{rtme-u'nylroxazole (3i) al-so suffered sone d.eccinoosition in the presence d n-bu'cyi iithiur, bu'; ar1rl subsiiiuieC. oxazol-es y,¡ere conpJ-ete,'¡r stabie io thj-s reag,ent" T,abei] eo oxazoJ-es, for rnass sÐectroinetric siudies, have been obtarned- by tr.eaiing the orcazol-es with n-buiyi lithrun fol-l-o¡¡eà by deuterir:rn oxide" TJ:e aegree of jrco::pcra'clon, af,d *r,he d-istribubion, of deuie:'iun Íor severeJ- oxazoies is l-isted. i:r labÌe 18, frora v¡hich ii is clea-r ihat tìrere is a wide ve-riation j:i r;he acicì-iiy of these compouncis. these results incl-icaie that a hyàrogen at C-2 is the nosi aci,fic ir: tire conpcunds st'.rdied., foll-cn'¡ed by -Lhe hycircgens o-Î a Z-me'c}iyl- subs'cituent" lirese resul-ts age in agreenent ,,rith ine caicuiated- ':-¡'- electr.on C.ensjiies (faofe 12) ",',-'niclt preåic-u ihe fo.'u'esi eleciron d-ensity àú \¿- lo In agreeneni 'wiih iiterature re¡or-¡s1150 b"ooj-na'üion of the o;:a- zo1 e ti:'¿ v,¡as fourxi to occur reaÄily a'; C$ " The reaction wa-s specifi c for'¡his ¡ositiorr: bro:rninai,ion of [-phe:rylcxazole (¿4) gave no -i:race of 2Jcrorno*L-pheny..l-oxazol-e, ad- even u-nler forc:-ng conaítions no br.oni-nai-ìon a'; (zl.) occi:cied.. ccntlary â¿: earfj-er ,.oo"i"5a it rvas fo'ùLrrci ',,hai; "o 2s5-1i'che'rTrLoxazoie (ZZ) und-ergoe s b::oin-ì natron 'u::d.ez. r¡igorous cond-itions -Lo give l--r:r'ci:lc*2rldipirenyioxazoie (5,r,,¡. the reason for iÌre nai.keC- -11A- TÀBT,E 18" Deute::iun d-ist;'ibutjon i:r oxazoles on treatnen-t, lvith l-ithiu¡n at .-a^ *5r U enc. c-ecomposr tion vdih deuierìun ¡ U.}-4tÀCi^--i ^ o C ornpo'.:nô lime Products Incorpora- å.: /,Ji\ (ar_ns/ v-LvLL^* Vc) Oxazoie (1) io S ixteen uúd-entij i-ed. 23terJ-:fv¡nethyioxazole (fi) j6o 2-d., -Me thyÌ-.L,5 -dj-ne ihyi- bU ¡- oxezoLe |-Phenylo>razole (44) 12O 2Ã,-lrPhertYLoxazole '! 2-i*ethyl,-f-phenylc: J¿-ìlethyl-!-phenyloxazoLe (+l)lZO 2-ð-^-L. -\le thyi-5 -pne nyÌ- '100 ov-azoLe *-hyL- '100 þrf;)iphgnyLoxzzole (z^t) lo 24'n-Ip e! -D i:ne oxzzoLe 2r!-Ðiphenylo>:azoLe (zZ) 7ZO 2e!-Diphenyl-o:cazo'le ¡r'eference for bro:rination ai C-l is not o'ovious frorn the cal.cu-iaied- Fí- eleciron o'i s'c¡'ibutioäs (Îdo!e i2); che expla-nation ney be :-n the abi-r ity of t'ne tä:oge'o lone-pai-r to ccnjuge-ve tr:-.i;hC-i (ta) 'out not wi¡h arry a'vbet position of rhe oxazoLe rÍ::g. 1 N .<------> \ U c t1 z) 1tr 2 4ta As repor-tedr'tt t¡-lw Dieì s-A1d-er a¡l-Ciiion of rndl-eic a.-jtyd-rid.e to ihe ir:e-r,hyl- oxazoies (JO, j1 u 3i, 60) occurred read.il-y to give subsii'cuteå cincho¡ieronic acicl-s (pyrid.i:re-Jr\-õ.ecarbo:rylic acid-s). the adåiiion r¡as i::ri-fo;nrly 'ùnsuccessful with phenyl subsirtuteå oxazoleso In oràe¡ to determi::e u'hethei' the wrreaciivity of aryi oxazoies towad.s d.ienophi-i-es was flue to s';ez'ic nind-ra:rce, o:: tc el-ectronic effects invoiving the i¡rcreased- conjugation of ihe oxazol-e ffi-system, a series of d-i:nethyl-i- /-- bì:tyr- l) ( - )>)-^\ a:r'å d.imeì;hyl--t-butyj oxazoles (41 - tJ) rrere'si¡nthesised- a::rl. tneir reactj-on v¡ith mai-eic aiùyd.rid-e s-bud-i edu the pi:od.ucis oÍ these -reactions, togerher lvith ¿ui.iosê fron the aCdi-uion of ¡:al-eic arrÌryd-rid-e to otiier ah/i oxzzc\es, are given in ll'able 19. Tj-rese resulis ind-icate that i,he cycic-ad.d-ítion to oxzzoles is sensit-ive io a b"uÌþ substituent at C-2 or C-[, but noi to one ai: CÐ cf tÌie oxazai,e ring" ?his fact, together lvìth the cbservecl ad-d.it-] on Te.Lca;clLs to ihe 2- ¿r'ö. [-i-butyi ccnpo'.:ncÌs, i-nàicates that ';he t-ransiti-cn s1;¿i';e Íc: ihe cyc-ì-o-aLd-iiior: 'ro oxzzol-€js i.lay be sj:t'-ia:' to thai d-es- criberl Í'or -Lhe sel-f-a,rLr1ition of cyclopcn't-Ìi""",j58 ÎÌris noàcl rcquires a;r endo-rcl¿-1;ionship -5eùr,,rcen tlie oxazol-e eurd d"ienophil-e, wi-Lh en a:rgie *112- Ti\BLjì 19. ?roducts from ad-d.i-tion of maf-eic anh.rd-rid-e to ai-kyl- oxazofeso Subsi itu'c :; on Patter:r ! !9UUVV Y:.e:c (/,) 2rj-Dtne¿;ilf (¡O) 2 -D )me'chyic inchcine ronic acid. BO "J 2,r!-DimeihyL (3'i) 5 r6Ð!ûethyJ-c inchorneronic acid- OU -iny! (J ÕU 2 el¡ rj -T : i.ne j) 2 15 u 6 -1 r i¡rcthylc inchorne ronic oni Ä *o 2-i-B utyJ--[ ri -C.irire tnfl (Sl] 2-íåu!"y!-$, 6 iree thyi* 4o cinchorne:'onic acid. 17 L, 5i-B u-cyl -2 s5 -d:ut e'ciryf ( 5 8) 6 -i-a uty] -2 z5 4isr,ethyl- cinchomeronic acid ! -i-B utyi- -2 eJ¡Ã):retn¡T (Sg) I -i-B utyl - 2 t.5 *à:r,eihyi- l+9 ctrcì:omeron-i-c acid- 2-i-Ðuiyi -ta rJ -C)net-nyl (41 ) sta-rti ng oxazol-e in-t-Ð utyl -2,j -c,=sne tnyL (42) starting oxazo\e q, (4J) yL- ^/5 J -t-Ðú,yL-2 ]a-Ctmetiryi 5 -t -B t:i, 2 u - ð-i:nel.ny!- ci:rcho:nerouic acid. 2-\liethyL.-j-e thorly ( 60) j -Hy ô-r oxy -2-ne t hyl c inch o - t+6 neronic acid- cf anproxx:.aiety áOo b.irr"elr ihe p1a::ies of the nol-ec-'¡]es (nig" 4i), Such an a-nguJ-¡r reiatiorrship ad-equately òescz'ibes the observed subsiiruert effecis, a::r.C. ihe reaction of (ú)';¡rth nai-erc a-,-:hyàrid-e maires a:: e>:ò* erra-rLgeñ.e ni of ihe two ¡nciecul-es r:nrilcely, 447 N Fie. /+1 " Tire f a-ilure of )'-nethyL-:2-phenylox azoJe (4-/) io unö-ergo the cyclo-ad-d.iiion reaction must be ascribeå io an elecircnic, raiher tha:r"r a steric efíeci, ð.ue perhaps to conjugation of the l-pirenyl group rncr.easín¡; i;he cì-ei-oca]-j-sation energy oí the oxazole 1T-sysie¡n" ÎÌris means inaL tt is not va.lid. to ascribe ihe inertness of 2- a:td- Ja-phenyl axezales to cycLo-add-ition to a sterj-c eff'eci" In f act, nocl-el-s inC.icate íhat r,oe i-but-yl oxazoles arce more Ìrind-ered-'cìr¡rl the phenyl oxazoles, ar:c1 hence it app::ars that the urreactiviiy o:f al-l phenyl oxazoLes ts¡a-rd.s cycic-a-C-cition i s d.ue tc elecironic effects. On heaiing J-rrrethyJ--l¡-phenyloxazole (t6) a-ncÌ mal-e.ic a:rtr¡icl,r'id-e in boiiivLg r¡¡lene for 12 hrs", a 1jlí yietc of the ai-àition procruci -11]+- ¿' !-rreihyi-í-phenyici:rcho¡reronic acj-d. (ø) is obtarnedoott^O ff the sa-'ne reacìia-nts are heated. in benzene (7OoCi a¡rcL ir:reCiated- with uitrarriolet light (¡eOOl) then (8'2) j-s fon:red. )n 76'¡/" yielC' irradiation t'iih uov" light ha¿ no effect o:: the cyclo-ac.C.ition reactions of ihe aflqfl- axzzoles, a:rC- ihe enhanced reac¡ion r,,rutn (a6) nnay be C-ue -uo excìta¡ion of the ir- el-ectrons loivering the d.eiocaLisaii-on energy of ihe rf -systern* fhi-s v.¡ouio confi;'n the expl-a;ration of ihe u¡reactivity of a:'yioxazoles given aboveo IÌolvever, (46) vras the only coirpou.-d- to show ihe er:l:ar:.ced reac- i;i-rity oll Lr.ve :-rraCration, a-nd. ii woul-d. be pre;rrature to drar,v nore tna¡r tenia-tive conclusions froin this obserr¡ation" T]:ese res-¿l-ts do show ihatr except j¡ ihe case of very bu1þ groups zt C-2 anC- C-f, s-¿eric hindra:rce is noi a contz'oliing factor j:r t|ne cyplo-ai-ö-ition of maJ-eic a-nJ:yd.rid.e to oxazoLeso ÎY';æ41¡-n-TA-, 4t,ta G¡ÌriER.,¿j Àfl n:ass spectra uere de-bennlned lrith a-n Hiiachi Perkin-El-.,-ner RÌILT 6D d.ouble focussing Ìness sì]ectrone'cer ope::ati::g at 75 e\l ('.:.r-Less oiÌ:.e::¡¡ise specified.) with e sor.ì-rce 'tenlreratuce of apprcxinaiely 1!Oo a:i.å a:: i¡i-et tem-oe;'aiure bet¡een ioo anci 2OOo. Xxac; mass aeasue¡nents .¡¡ere deterrninec with either ihe Rlfri 6D o:: I'u-iih a:r A;E.f. l,{S! inass specironeter usi;rg a resclution oí 151AAO (lCn vetlsy definition) -','¡i-'ih he'p¡ ¿ic o s af l-uo::ot :'ibu-byi ainine p :-airg ref e z'e nce nas se s o "or, Aii i:ie cxazoles exenine¿ (v,rith the exce'Jiion cf ZrJ-dtp1rcnyL- oxezof-e aað- 2|¡rJ-iriphenyLo>=zzoLe v¡hich ';ÍeTe Tec-lys¡aJ-liseo) .vere pu;'ifíeô. by preparative vapcirl' pÌrase chronatog='aphy (us::ig ¿ 20 ft" 3A/t SESO col-urr:r), a-ìid- add-ltronal-Iy checlieo- by nuclear magnetic rescnance speciroscopy. The nuciear rnagaetic resonaûce Speclura were recort'red. on a Va-ria:l DÀ*50--iL sirecrroiiìeier operating at 6O mc/s, vith teir'¿ureihyisrla:ie as a:l int:;.naj ¡.eference. Àir spectra vrer:e recorrleå at a:,lbierrt ternperatur"e z , ¡ '¡ca" i)-'¡^Cr " lire soivenis Ío'r the soiven'r; sh-,fì;! siuC-ies 1"¡ere of anal-,vi!- ce,1 ¿tzùe, fuz"t?rer d.istiiiecj. a:d- d-r'ied-" À11 ccncentrations were accu:'ate TC + )7oe Irt'':ra-red- spectz'a \¡.rere recc:-.Led- v¡ith a ?erk-'n-ILnet 237 s-cectro- lliej-,'in¡ ::--"""noints vere ceter:nìneâ in caaill-aries in a Ga--lenì.-a-'r1p apnanaius a:r1 a-¡'e unco.rr-ectedo -"16- ii4icroa-nalyses lvere perf or:ned by the AustraÌia:r Mi croar:ú;,r'i;; caJ- Servi ce, ]'IeJ-bourne. iúoLecula¡ orbrtal cal-cuiations rrere ca::ried oui on -i,he C.D'C. 6l¡OC conpuie:: of the University of -4.d.eiej-d.e cornpuii-rrg centre2 usi-ng p:'ograir,rnes wriite:: in Fort:ca:r Ii7" ¡-J Ar:îãD. ¿ v.ttJu M\ i o 2rJ-Dtphenyl-oxazol 3 lvas a purií'ied. corinerc,. a-l- sa¡nple. The f oiicwing oxazol es rrere s¡mt:resised. by repor-led. procedures: 2-7 i6O _ 4q oxazcLe r'' /uj-ãj-nethyicxazole,'"" 4rj-airethyl e'r¿2e1 e r'' 2rl¡rj- irlnei;nyJ-oxazoie ri9 ir-r-btt-uyL^2r!-d-ímethylo>:aza1e116" 2-í-butyi-$- _ i62. 2C^ 19 r:erhylcxazoie , - l¡--pheriyi oxazol_e t-- 2-t-=-a.riyi-ja-p,henyioxazoLe,'- ' j-nein¡L-þ-phenylcxazofe ,2C L-."tr,yL-J--citenT\cxaro1" r20 5-^r-.-ny!-Z- t,4t ".41u t ;i:eny l cxa zol e r''" )* 15 -t::::e th¡ri-2-phe r¡r1 o>: azci- e r' 2 15 -Ci:ne thyJ--ç- n'') 20 lhe:rylcxazole, ' j-e:hyL-a-phenyio: g"Ðz'cncli=tones rvere prercared- by star:d-at"d. rne'.',hcd.s âtrå had- boi-J-ing poiriis ,";;ent n¡:-th those r.epo:rted. :-n the l-iteraru::e. Pi"elar¿,ti cn oÍ Äceioi l-rs ancl Ace-l-oin esiers 2)-:IvvL Ë.-; --^.--.-â..!u,_,/ iiuL zn-?_-cr-e he¡toa;:, ?ctassi'.;t heptoate (Sg g) r,vas a.d-d-ed- to J-bro;nobuia:r-2-one (31u"5 g) ^ /,- 1? e-;!\rî-c:- \',24^ r-:-)^\ contain:_ng 2 dro;rs oÍ concer:traieo s-;ì-pìrrric ac:å, an¿ ihe mix'¿ui-¿ stirled. ær,1 heaiec-'¡::..ler reí'i.Lx íor eight hourso The -i¡as ¡'eact.-on nitiurr: coc-ed, í"i-liez'eö-, anci- the sol-vent r.e:loved- '¿:ri-er. red.uced. Þressure" ?he ¡esitj-uej- ye.'io,',r cii ,¡¡as i_isiiiiei -ìn r¡acuo io ¿â5 give J-h-,¡,*roxy'.o'{Le¡r-2-onc 4ep'coaie (i7 go 37/ü, b"p- 125-128o/'t2- rrctHg" (3cr-urd; C, 65"5; ts-, iOo0. crn -Ll-tt20O z.eo-u:res C, 65,95; rt, ..a"ail¿") À¡ 7 ne-l'l-i-cne û To a stir¡ed. solution of n-hexyl .l-ithir,¡r [f"o* iithiurn (t;u g) and n-hexylbr.onioe (l5S ù] in ether (5OO n¿) ai -1Oo .¡rcle¡' Crï Or-free niti'ogen, rvas aC.ded- a soiution of lactÍc acid (ZO S) i:: e-oher (tOO nr) over a -oericd- of 'ciririy nl:utes" The lenpel'a'ù.1-l'e v,las kepi belolv -!o auring the arid-ition, ihen the nixtul:e lves stirred. a-b Co 'Îor three horrs, ¿i-l-owed- to corne ro rooin iemperatu:e" a-no siirreC. fo-¡ a-ä ¿i.d.itronal- five licurso l.ãe sol-tìtion was cooled to Oo, d.ecornposec rviih I'va-ber, a:l1 the eij:ereai- layer sepa-raiedo lhe ei;her layer vas wasired. vu-itir aqueo'Lls so,1j-rxn hyd.roxice (lt"), ctiJ-uie ir;.i.rcciùo::ic acid. (4), waiel, and. ¡hen d_r.i-ed- (i'la^SC. Rernova]- of e-ihe:: pnåer red.uced pressu¡'e. ga\re a '2!L' ) " the ye-r lov; oil, whicÌ: on distil-iaiiot: :+ v-acu.c gave 2-þydrc:'../-nona:r:l-otlg (J"7 g, '!?i) b"p" 6-87"/3.8 m:r äg" lhis ccnpoi.md- .ras cìiaz'acier.ised as the aceiaie (preoa-reo- by t:ea'snerrt of the keio a-l-cohoi vith acetic -0,p. a-rr.ry-cLriae in p¡rr';fl;ne), ge-g|"/g:rr:n Hgo (l'o'.:::L: C, 6'0"15; ts'2 'lOoO" C,,E^^0, requires C, 6i"95; ñ, 1C,C57í") use cf lactìc acio î ether å¡ ¿v ) "1,?" ¡z-r,= i nt:?-¡'\ or^ -:)slìits o -4, 3 -.-wu ro r' ¡u'c ¿ t- 2- c rte '; l::rct;:;rf ac¿ ; ¿te o ?raca:zà a^s Íol the rre;;toate' j-5=or:.obu:ar--2-one (¡l g) ga\¡e /.. *" -::ne ^ 1 ¡n - .-_ L-_ :" a;h.-.Lac e -- -.C ,< ^,i';cr I'cll-u' ¡ ut ¡,:.r-2* c ]': e i ai e r.+? 9r ---.-\þ'i';¡, Ð,-r" l)-lr lÕ"2 ::r:!:9" -119- i-'cut rat,e 3Ær'circrvt¡ ut, xt-Z- ole " ?repa-:ced as ío:: ihe hepioaie" i-Bronc'ou'ca:Y-2-orrc (Zi g) and pcrlassir.m i-.¡aJaaie (Z+ g) gave l-Ð-SroxJbu-'a-n-?-p::.e-¿:Þg!Iabe ([1 8s 4tiù r'c,p. 61,5-624i1o6 nn-n Iíg' (Founô: c, 63.0; H, 9o29" ciñ^.qaj requir-es C, 62.8; ';, 9¿61a") Pi'eÐâJâi- cr1 cr 0xazcl-es., o:< az or e 2*n-¡Iexv l-*l' _"5 -Cirle ihvl \ )L') " J-i{ycro;çøì:uia:r-2-one heptoaie (17 g) ærd. an¡roníum acetate (lÕ g) giaciai acetic acii- ("i20 nú) heated' w:dez'reflo< for two hou::s" in "vere The cool-eC. soiuiion lvas *oo-.i::ed- onto ice (ZOO g) a:rd ext¡'acted- ruith etirei' (å- * ,,OO ril)" lhe etherea-l exiraci r¡ras rl¡ashed wi-th lüarCO, aqr'traiec' anC. -ul:ren d.rieô. (liarSû,)" After removp'l of the e1;he¡'througþ a:r efficient fraciior-rati.ng coiu-'n:r" ihe residual- oii v¡as ôj-stilieo in vacuo io give r;n iíg" ?,^n-nexvL*ì'""5 -'ú -1-h lti (7"55 g, t+s)í)¡ bop. 91-92oh+"i (For.r:rd-: C" 72"9i H., 1O"5; Ne J.5" CttHtr¡{C retuires C, 72"9; f,-' 1a'j; \ .|i¡ -!" -.¡:fic") 2 ,i-,t::r.eli'-:iL ox¿.zole )))o 2-,:¡d':'o::ynocan-J-one (5.3 g) zcetyL chlo:'i-C.e (Z t¿) ard r:yriå:ne /¿ c' *:\ .'.-'-^ L^a"ed- rvas \ . þ) it¿) vvu! u rlv u:rcler. reíl-ur for tl'rirty ri,inuieso The solution ccol-ed, dry benzenc (25 t't) adOed, ihe sofven'ú remor/eC. u.r-lder red.uceà ìriessure) a1o -th.e c:'uie es-be¡' reinai::inge toge-ther lrltii a-n:roniu¡n zce-uåte (ZO g'¡ r'.'a-s ci:solvec in ¿\:aciù ace-"ic ac:-i (JO:::) ¿:rà re;-led-'.n'ler r:efl-ux íor nineiy minutes" After cooii:rg, the sol-ution was r:or¡''ed. onto ice. (jOC/ -.^^ g),\ extracied., v¡iih ether lZ/ ^ x iOC rJ)r\ , i,ne ex+uTac"i washed wii:h NarCO, acl, nater, a:ro then C.risi. (XarSCu) " F.e:novaJ- of ihe eiher througlr an efficierlc fracrtonatìng colu¡nn a¡C- d.istillaiion of ihe renai:ring oü in vacr:o gave (2,6 g, l*51Ð, b,p. 70*760/ 2"6 rm lig, (i+o',mc: C, 72"7i Ii, "iO,/¡; Ne 8.2" ClfHiUlíO reQuires C, 72.9; F', 1C"5; N, J"f1'"") *2 -;hl/." o:razol-e (56\ 5*n-I{eä1¡-ì ".r¡.-ij:re " 1(f Pre.oared as Íor (SS) " J-IIyd.rorlarona:r-2-on.''" (6"0 g) gave 'a"p" ('r "7 z, 25fr) , 19-gao/4 ¡:rr,Hg" (-ror-rta: Cn.H.oNO :'ec¡-rires C, 'iO"þ; C, 72,85; E, 'tA*\; N, 8,'l o |, .) 72"9; ï{, -- \ .i\ y l" -,Íf/"") ilt-¡LoxzzoL" ( 2*í-3t:',:t7-1,,2 -di:re i7') " ?repareå as fcr (S+) " J-Hyaro>q¡bu,e-tt-2-ovte i--outrate (¡0 g) ut-f:-*.1:,5 ('t5 t b 6o*5 Hg 2*i.-"3 -åim,:';hyio:cazo-l-e g, 5/;) , .p, o,5o /8 rni " (i'o',rnC.: C, 6)"8; *, 9"5; Ì{, 8.6. agn.,nO re'1ui:es C, /C"6; l, 9"9; \, 9"'ii¿o)_ ..i, \ A satisfac-t'og a:ral-ysis could. not be ooi¿:ned for ihrs con- oci:tå, at-thcuga ]-is mass snec:;z-trn, r.¡trlofo specir'.:rn, a-nd v"pnc. ceronato- gra:l ina-icaieà that :-t lras e p-¿re salnpie a:r1 h¿,C- ihe assigned- str"Lrctu¡'eo j *i*P ur-,'r1-*2 e'c'ny1 ( r/.r-å::¡r c::zzcle Jg) " A soiutior: of J-orono*,!-rnethyihexa-n-2-one (ZS"j g) a.rd. socl,ii::r acebeLte (ii/", g) in gJ-acra.J- acet-ic acrd. ('XiO/,'-^ rù),-\ r'ras s-tin:eu æ:cl heated- "u-r:d-er reÍlu:.c for n-'ne-ûy nirru-;es" 'fne soluiion was cccLed-, fil'terec, aiïrnonl-r.;tn ecetarüe (60 g) acld-ed- to the fii-irate" erld the sol-uiion heate& wri-er refl-'ux fcr a furibe:: irvo hours. Îlre soluiion '.'¡as cooj ed-, pour"ecl /t- \ onto ice (5CC^^ g; y arld- ihe aqueous laye:: extractecl l'¡iih etìer ¡j x 1AA nù) " lire coin'bi-ned. ethereal extracts r,vere vasheå ',,'rith wa-ter, ITa,rCO- aq, d-r-:ed. (-ra^SC" F'enovalF.enoval- oÍ the ethcr 'uìrrcugh alÌa-* el-ia-^--"' r';ater, a:rcì ii:en ' ¿ tJ;), creni fraciionating col-i:.'r,n a:rd- i-ístj-l-lation of the resí ô -: D-.:--a ! ./,,\ ¿- iJè) Ju"\/ L-i,, I oXazOIe \l.r'l I o Frepa.reo a.s for (l¿u) " i-iIyd.r'o:qybuiat;-2-cte tr'ùneinyiacetal;e /,. - . ryr'\ - -r -nC l 36"2 s) g.^aÍ e 2-i-bui j/L^l,t-,5 -d-!netÌiy1- oxzzol e \-J o", 8t 4t,") y Ðopo la-/ö / /-- 'lij ri:] i:gd (:c'r:d: C, JO"J; i, 9,43i lde 8.9. CCI:,-\-Ci1t requires C, JC".6; \ Ì;rt2 )qt)lic 47, r\yirt o)oi/ro) ¡r.í a;h-,1!o:razct ( ¿,-l: i.:.i- IL-2,j -ù)::-e e ¿,-Z) " Prepareci. as Í'cr (Sù " c/-Bromo e*uhyl t-butyl icetone (+8 g) gave (zl n-rn iíg" l-*'u- c'trti1 -2,5 -J::rcti\ÍLcxazol-e "to g, 57'ù, bopo 77-7Eo/iJ (lrour.*: J, JO"'ij; -, 9"6; --ie !"01¡o Cqr-,-:íA rec.u1:es C, 70"55; TI, 9.9; / t/ lÍ f: .'î lC- \ !,t )ot4/)c) ( 5-'û-'Jc';, ,r1 -2 -),-:-i:::e;Ìr-¡-ì o'.a--o:e :'-j'l . ¿(- !)te'a'"-:cù es '!c: (lg) " ciJ-'onc ::e';oyl neoncniyl -rctone''J ('tZ S) ,¡ 5 * u*-¡ui --l r.t-1--dt.:rlic r'loxazoic (-rou-d: C, 55J; H, 1o"2; Nr 6.3o C"E,-i\-O rec-u*res C r 7C"5i nr 9"9; / t/ ^ , E t 2 J-¡--d i¡re';hlrl or: azole*J c arb c x-¡1 alu ( 6'i h'¡i e - e ) " Prepared. as for (¡g). d-Bromo eth¡riacetozceiz-te (+Z g) guve etilyi Zr4-U¡ietityLoxazol-e-J-aarborylate ('î g, 3ii;) y bop" 8Oo/1.! irrr Hg" 4lQ /--. ,uu -- /.- ,- /, (: ii"' inop" ,5i56--ral ) " (iround.: C, -/55"ì'j1 E, 6"\';; N, 8.1h, Calc. f or' a -,: ìt^ I n / - n -./ \ UE[i1r\U3;" .t )4"Ò;=l 11 t óÐ; !\e ó")/.te) 5 rcno*L-*::he n'¡l-cx ãzo1 e -B 6z) " To z st;rr.e,1 sol-utior: of J¡-pÌrenyioxazole (++"f E) i-n carbon teiracl:J-orid-e (iCO rnf) contajring d.iì:enzo¡4peroxide (tO rng) va.s a,åC.ed ld-b¡'onosuccj¡¡-¡riåe (17-S g) cver a peri-od. of ùuvo houi's àr rÕþÍl tenoera- t'L.r.reo The reaction nixture lras stirz'e,i- fot z furtl:er h¡¿o hours, fiJ-tered., tite sol--,.en'b, re,'nc¡øeC, a:rd tne oii renaì-ni:lg v,¡as su-þ.-i¡led- at BOo/C"Oj rm ïig, ã C, 4-3,!+; 71, j.C; li, 6"1i Br, J5"3" C^;{,1\03:' reo_u:tes C, i,8oE; =,J., 2"7t )v 1Ì ¡:= '= -ià /'' \' :.t woL)>I - 'Lt-- )-)"ú1 ") Îr'eatlre::t cî j-37or-c-L-pnenyloxazole iriiìr nctnyi n:a;no:ir-r: -, oà=c-e qua,-.'cita;iveiy c:oi.uce5. j-::eihyr-L--cheny-io:cazol-e (a5) iclen-;icel .;,itr ¿cl arrihentic specifien (v"p,c o ard i::fr.ared- specir:r)" the prcd-uct sho-;,¡ed- only oi:e peak Ín ihe v"p"c" chro:rraiog,ran using col-uui 4õ7 condj-tìonsu .;rhich fu1ly resolved a sta::d.arcl- m-ixture of l-rneihyi-L,- phe nyi ox a zoie, 2-mei"oy7-1,.-phe ny-r ox a zù"e (S)' lrd- 2 þ -õ"t:rc thyi-+- .chenyioxazore (ú). Ì."3romc*Z,5-di !v \ )tLJ ø 'Io a sol-ution oi 2r5-diphenyloxazole (4-.;, g) in gJ-aciaÌ acetic acid- (1CC m1-) boil:-:rrg ulrd.e-r rqffui:<, lvas aådeC. oveT à period of one horr, j-n rn'as a soiuiion of bronjo" (j "Z ù ecetic acid. (15 Íì!)o the nrJxiure heated- lot a í'u:l¿her houro ccoled, and a so-i rC' ¡z'ecipitate remcr'¡eöo lhe fittrate v¿as ricured onio ice (eOC g), erL-rzcLved- rviih ether (J x 1OO û1¡), e:.C 'che ccnibj:reå extrac'cs rvashed wi'ch v¿ate-rr l[arCO, aq, wa'Ler, and. thel-r d--¡iec (i'la"SO,.) o Removal cf the ether ieft a sol-ia rvhj-ch v¡as chroi:ra'cog¡arrhecl- over ai-lx¡tina rn Lighi pe'crol-ei-r¡n:ethez' (92 t 8) to give ',,','hicÌl E PJ--lJ-tt.t ì*1-- nyl (t gt cryslaliised- frorn iight t t) axazalo "t 3i7Ð, peirole',:::r as coiout'iess neeåles, nopo 7o-7tro. (3ound: C, 5O "2; n, J.j; r\i, L,6 j Br, ^a25.J" - requires Ct 6A"5ä H, 3"L; N, 4"7; Br' "r:rr,,Ol{OBr 26"61[) ?he non,r.o spectr.r¡ racked ihe singiei aic ö7"32 attributed-'co l-ne 4;¡ of ihe cxzzol-e sys-ben" !r-'crer:l:T,.:ri- lr ronina; i on oí Lv,J -d::pne. Eyao¿p4sl-P l 1)-" (1) To a sl;i:¡.ed so,-ution of L,!-d-iphenyloxazole (ZZ g) a:d C.ibenzoyL- (,,j j-n carbori 'cetu.achl-or.ide (t¡O n.-) , lvas ao-d-eô Ì{-broinc- ?er:oz.de ^g) succuiiriàe (t7"8 g) over u¡¡o hours ar ïooiî teinperanui:eu Îi:e reac-t:on ir:j:;,'¿uie vas s-cii-¡'e,L a f'ul¡hei't-.'¡o houz's, f-iiiered., the soirtent rer,ovei-, -iU.- arul ihe resiGuù oii crisiilled. in Iacllg" larJ-Diph.er,yLoxzzoLe (18 g) , bopn i 2i-126o/OuO6 i::n I{g, r,vas the oirJ,y prod.uci, e-nå was icienticai- (v,p."u and- irrf'rared. specir*n\ rvi-th a:: au-uJaentic sa::rpJ-e of 4r5- d-ipnenyioxazcLe o (z) Srcnj-:ie (t6 g) i-n glacì-ai ace',ic acra (t5 mI) ,,vas a.i.ceö. d.ropiri-se over ninety ninutes, to a sol-utlon of 1¡ri-ciipnenyio: '¿nd-er reflux fot a furLher three ho';rs, cocì-ed., pclrect onto ice (ACO g), a.rC- exirac-¿ei- witl: ethe¡' (L n¿) Ihe con-c jned- extracts rn¡ere v¡asired. " 7, " v¡i-uh r'¡a',e rt îíarCC, aq, water, ãÌd o-rieo (ifarsor) o Rernovai of the eihe-¡' anC- C.isiill ation of ihe residuaf oil- in vacuo yieid.ed. J¿, i -C.iphenyl- ci:azo1e (i3,5 g, b.po 125-1264/0"c5 mm Hgn îìri-s proc.uct 'ras 75%) " identjca-l- rvi'¡h an au-uhentic s>*mpie of Lr5-erpheny]-oxazcle (v"pnc" a-rd- inf::'areà specirum) , ara-c :-on -L sotopi s a-11.y' T abel-ied- C cnpc'.rnd-s ?rer of " 2 to> Pr.r:-oarcci- frorr, ?-rlpr6<-r-anlLine by ihe raethod- of Ìliliiams, et a-l-, .D I o a) l-cirlori ce, i)-,'.^',¡n^ ! Lel)'¿L i:i o_u¡:rtitarive y:e]-à b;,r oxiCLa';'ion of çr4r5-ò-.- 'oenzùô.e|ryðe -t¡ü!t KIi-r,O, ac,, forl-o*eä by tr.eainent of 2r\r5-C.r-benzoic acicl-',.,,{ih Sæf2. 4õÇ a? b L (r' CTLZA\|1. Prenrreô!¡vv4v*) f rom 2 r+ t64,,-benzal-d.ehyd.e by ine benzoin ccndensation" Al-1 'che iabell-ed- axazoJ-es tere proô-uced in high yield- and pr.:.rifieC- by preparative vapour phase chroroaiogz'aphy" ?--u3., -ìrPb.e nv-t o:iazo ie ( ¿J-'-b)" [-?henyio:.-zzaLe 10"29 c) in eiirer (io nf') ur.ôe:' drJ'Or-free nitr.ogerr, was treaied v¡ith n-butyl l-ithiu.n Iprepared. from n-butyl bromicle (0"6S g) a¡c lithi'un (0.086 g) i:: ether (¡c nr) ] at -650 for tr'¡o hour:s, The corçlex was d.ecoinposed i¡¡ith deu-¿erirnt oxid-e (5 ,'t), ihe ethe¡'eei la¡rer sepa:rated. a:rd. C.:ieò (tl"¡C") " Evapora'i;ion of the er;he3 gave 24-,r-[-phenyi oxazole, bop. B9-roAohrrr:n ilg" (Lr6 a) -"1 -4 -liethr¡1-+-piren-¡1 oxa:¿oLe " As fcr (¿¿u ¡) . !-'r,lethyl-r,.-pi:enyJcxazole (o"iz g) Eave 2Ãr- i-nethyJ--þphenyJ-cxzzof ee bopo g7-B8o/O"O) nrn lig" -¿r-: -c th¡¡i-4-Fnc:,':¡,'1oxa:ole (i..J n) . ¡^ ¡.^- I' (.oðz AS ror \¿4 b) " Ja-Ilethyi-f -phenyioxazale g) gave Z-c,-l',- r.e',Ity\-:2-phen;rl6;"zc-,e t b"p" i O7-1Agaß nrn Hg" j-phenvioxazo)-e (2'ia) 24r -l ,5-D " ¡ p^.^ /. . \ r! ;-- ! ui tL,t: O) a Çe)-)LijneÌìJrioxàZoie'Len¡r]6;ç¿zoLe (Ue)(0.5S a) gzve 2_&,-L"a--! 12¿ -coPo c irhen;,ic'xzzcLe, 1J2-'t )Jo /C "1 nr-*r iig" -ìZO- I Loxazole h 2-Ìúethyi-l¡.-phenyio: -lt -ûïtie l oxe.zoLe a Prcpa:-ea as for (l¡.t A) " 2eL+r5ilr:rneii:ylcxezcLe (O"Jj g) gave 2-(At-rnei;hyi) -l¡rJ-ð.'nte-JrLyLoxazale, bop" lln-|7o/2O nmr I{g. Ihe mass spectrnnr sho'¡'¡ed- 6g; íttcotporation of deute::iurn, arrd. the r1"r,'r.r. specirlm incica't ed- that this v/as en'cireiy irrcorpora'i,eå ín'co one roetbyl group. -1, *fhen.'rf c:cazoie ( A soluiion of !-brorno-[-phrenyToxazcle (0"L, g) i-n ether. (tO raf) uas aC-d.eo to n-butyl- fi';h:-'":r Íor (¿+ ¡)] in at after [as "t.,."t -650, thirty second.s the reaction was quenched- by aöåition cf deuieriun oxid-e /- i,j :tL).-\ the ethereai Layer lvas separated, a¡tð- aÍ"cer rvork-up as for (lrl:ci) y;eicied !--o,,-|-pi:ertyisv¿2oie, b"p" 89-9ool, ::m Ìig" A reaction l;-,e oí no:r: than trirzy seconð-s gave sone õ,r-oxzzo-'e'o -\ / "¿ -/q.) o Prepa-recl. a-s for (¿¡"") but r,¡ith a reaciion ti:ne of ien.r¡-nutes" 5-3rarn-2-n:er'ny1--i--p,ncn;uie;çezoLe (C":,3 g) gave !-å,*2*nethyl*i'- Pie:--,rl çi'r^zo'3, :t-P" iia-j'o . *D ( 22a\t ': -2 -! inhenyLoxzzoLe " Prepa::ed as for (+") but with a reaction tj:ne of one houro i¡-Brcmo-2r!-d.ipkrenyloxazoJe (O.l e) gave J4-d-n-2rj-dípbenyloxazole, m"po 71-720" The nom.r. spectru:n l-acked the characteristic singlet at òJ,J2 in tlre spect::um of 2r54íphenyloxazol-e. phenyl) o),-azoLe (zla) " -D-^*^-^'r 19 DÐ^^.r^+ 4 rey4v* from d-.-benzoirt by the rnetho¡.i of theilig, !rvguu9 o hac bop" 19A-19U"/14 mm Hg" l^. / , ^ Z ( 1"\ ell.eo-t]-= -Phenyl) -L 15 -d.iph er,yLoxzzote Za) " 2r4r6Ã3.EenzoyJcl:ú-orid,e (l ð g) and benzotn (Z"l g) vrere v¡arnieC. or-r. a r/ater-bath lviih exclusion of moisture for one hour. the crud.e -) benzoj¡-d=-benzozte't ì.vas conver-Led- to (Za) by the nei;hod of David.son, 4.6L et aio'-- The crud-e produci was chrr¡rnatographed- over alunina J-n ethe::, a:dr crystaJ-ìised. frorn ethyl alcohol- as color:rless prisrns¡ flopo 115-1160. 1-,à, 2-D :æhenvlethryl- ene ( 2tt.a) -1, " É.eC-uction of d.esox¡rbenzo''n r'¡ith LAD gave 1-æ-,!-1,u2-diphenyieihanol, woícnr.¡as dehydraieö in Dl,iSOX70 ,-o gi-ve 1 --no-',¡2-diphenyiethyleae (ò.n- stiiber:e) r rítop. 12+-125o, The n.rn.r. spectrr;är ind:cated- quantita-tive i-trco-rÞoraiiqn of deuieriu¡r (,>9f/!' a")" t"c;à^-lresox]-benzoj-T:." A sol-ution oi'cr.esoxyoenzoin (tO g) j¡r ethei' (ZOO rças shaken -1 "t) íol' Ju1ïeilty-four hours v¡itìr aJ-rrni-na [tiholen basic al-uraine (fO t¡ ] wÌrich À ^ç) had been deactivated. with Ceuteriurn oxide (¡ t"f). The solution was fì-ltered, *9 *" process repeated. wi'th a fresh sa.nple of alunina (prepa-z.ed as above). The soiution r"'¡as fil-ierei., ihe ether removeo, a:-rà the resid-ual- lcetor're heated r¡:d-er refl-ux v,¡ith åeuterium oxid-e (t5 nf) a::rd. a..ri:yd.ror:s potassium carbonate (l ù for t-r,venty-four hours" The mixir13e was cooled, extracted wi'uh ether (Z x 5a rù), and. 'che cornbined. d.ried. (Na^SO, Rernor"aJ- of the eiher and. d.istillation of the exiracts ¿4- ) " i:roâuct ìJl \,acuo Bave d.r-d.esoxybenzoiJt, m"po 55-56o. the mass s¡ectnirn measured, at appearalce potential shov¡ed the incorporation of deuteri',:m to be 9U% dz, M an, 4o do" (z¡v\ -i ,2-DiphenvÌethYlen" " R.eduction of d.r-d-esor.ybenzoin wÍth Ll,Ð [as for (Z*")] gave 1'2'2- vrhich on dehyd.ration v¡itì DiliSOlTC guu" 1'2-ð.2- |,-i ,2-C.íphenylethanole 1 ,Z-iLphenyiethyiene (d-r-stilbene) r n.P. 1Z+-1Ða. the rr"nor' ryectnrn gl; shov¡ecr high incorporation of d.euterium (ca. 941 dZ, dù " 1-(z,l-,,6 Äiid-ii;icn of benzyl magnesiurn brornid.e to 2"ta,6-d3ao.n uad.ehyd-e ga:,re 1-(z , v,rhich on deLr¡rùr arLon v¡i th "4 r6-ar-phenyl) -2-p}renyìethanoi 70 Dlisc1 guu" I -(2,u,6-ar-phenyl) -2-phenyiethyiene (ar-stimene), rn.p. 'i2lr-'¡25o " the nass spectrurn recorf,ed- aL apr,earance poien'i;ial- snov¡ed- the i.euteriu¡n incoqporation to be 967; %t J% dZ' 'tfå ð"r, -129- - /^. -\ 1-(d- -Phe nyl) -2-ph e nyl e t Ì'lyIene t ¿IJ-CI) . Ad.d-ition of magnesium broniC-e (prepared. frrcn d-- - $-Éenyl bromober.zene) to phrenylaceia-lC.ehyd"e gave t-($-pnenyi)-Z-phenyleihanol. lhis was d.ehyd-rated- by heating ín Dxßci7O -o give 1-(dr-lnenti)-Z- pher¡ylethylene (5-stilbene) e ncp* 124-1zio " The n.nor. spectzum ind.icated. quantiiative i::,corporation of d-euieti". ( = 91" %)" (25 -9,1 O-Ðideuterophenanthrene ù " Red.uciion of the d-ime'i;hyl ester of d.iiùrenic acid. wj-th LAD gave 2r2s-(Az-hyd.r'o4nnetnyl)-d.iphenyi, which was converted. fo (öe) by nethod 1-71 j¡rcor- of HaJ-J- , et "l ""' The n.n.r. spectr"rm í¡Cicateö. quantitative poration of deuterium ( > 9fl. d,.). -^t jo- arar lvílnT) 7 vf l,*Jl^ Ml , a 2 15 ,5:Irin'eth-vlc inchonez'onic acid ( 86) . (t) A soiution of 2)+,5-tri:nethyloxazole (S"S a.eô maleic a.rhy- "7 d-riC.e (lO e) i-n benzene (70 Í11) conta-ining 10 mg of hyd.roquinone, wad heated r.:nd.er reflux on a wate:c-baih for forty-eigþi hours" the solutron 'was cooled- and- the solid. prod.uct collecied. by filtration" 0n crys- taliisation from v¡ater this solid- yieId.ecL 215 rí-trt¡nethylcinchomeronic acic. (B.o g, BqÐ, n.p. 2J2-21+o (L:to'io *.po zil*o)" (Z) A solution of 2ì+Ð-trìme-r,hyLoxazole (5"6 g) a-rd. rnaleic ar,rry- d-r'ice (tO g) i:: benzene (70 rnf) containing 10 mg of hyd.roquinonerlvas heated- unåer refli¡< at /OoC a:rd- irrad.iaied. wiih u.vo light (¡¡OOÐ in a Rayonet photodremics-l reactor for for-ty-eight hoi,i-r's" ïtroz'k-up of the reaction mjxtrre as above gave 2r5rl-túnethylcinchorneronic ac:l (J.g g, Bq"), m.p. 233-2340" A repeat reaction v,¡ith benzcphenone (toO mg) ad.d-ed. to the reaction mjxture gave iC.entical resul-tso 2 fi -Ð t:neih.ylcincìrome ronj-c acid " Prepared a-s for (86). 2t5-DineinyLoxazoLe (z g)gave 205- d.ir.ethyicinchornerr¡nic acid- (3,g g, BV\), n.p. ZÊ-z+5o iiit"156 r"o. 2)o6")" îhen ihe'reaction rvas carried. out ',¡nd-er u"v" light (:iOO8¡ ihe saune prod-uct v¡as obia-ined- in id-entical yield-. 5,5-li:reinylci:icho:nercnic acid-" ?repa-red. as for' (S6). [,i-Di:netnyloxazole (n g) gave 5,6- 4 2.1 d.imethylcinchomeronic acid. (1 .9 g, 8qù , m.p. 269-2700 (LLt "15i 262o7 . (louna: C,55.\2; H,4,62i N, 7"iJ" Cal-c. for CTHUNO', C, 55"38; H, 4.65; N, 7.1V".) Irrad.iation v¡ith u.v. J-ight hal no effect on the reaction" 6-aime lcinchone rr¡ni-c acid- A solution of 2-i-buiyl-4r5-d.imethyloxazole (1.53 g) a.rd. ma-leic a::uryd.ri-d.e (Z e) in dry toluene (ZO mf) containing 1OC rng of hyd.ro- qui^t:one, lvas heated. on a boil-ing vrater-bath for focty-eight hours" the reaci;ion mixtrlre '!\¡as cooled and. the solid- 2-i-butyl-5 o6-d1î'eth.y1- cinchcnerrcnic acid- collecied- by filtration. The cn*d-e material r,''reigþed- 1"21 g vrhich represents a yield. of 46/r. The cornpound- v¡as very insoluble, bui a smal-l amount crystalliseC. frorn glacial acetj-c acid. arld had. m.p. 19a-192o d" (rouna: c, 6o"5i H, 6"82; N, 5.t+5: clflrNO' reøuires c, 62.1; ,t, 6"82; N, 5"57/".) 5 -i-B ut vl-2, 6-d-ime th inchoneronic acid.. Prepared as for (82) " !-i'Butyl-2¡&-dimetltyLozazole (4..5 g) Eeve 5 -/. 6 (1;8 -i-b ut vl- 2 -d.in^,e t cinchonne rr¡nic aci d ",4V/")" the acid. airer crystalisation fron r,vater hai m"p" 236-238o ù. (Fo-,.:::d.: C, 62"37i H'' 6"Ø; N ctfl rewj-res c, 62"1j H, 6"82; }'i-, r 5-63" f{ou 5"5T1") 6 :: ac icl- -i-Ð ut:'¡I -2 15 -a-:neth.r¡Ic i:ichorne onj- c " Prepared as for (gZ)" I¡-i-Buty1-lr!-d.imeihyl-oxazofe (0"4 g) gave 6-i-lutyt-2t5{tnethylcinciiomeroni c acii. (0" 15 s, fi?l) mop. 228-2310 . -132- 5 -t-B utvl -2 .6-ð,itt^ethvlcinchomeroníc acid-. prepared as for (gZ). 5-t'Buty1-2)+-ð,imethyioxazole (1"6 g) gave 5-t-butyl-2"6-d.imethylcinchomeronic acid. (1 .l* g, 5ú) , rî,"po 218-22oo a" 5 -Hvdroxv - Z'-rne th,rlcinch orne ronic acid Prepared. as for (S7). 2-Methyl$-etho;groxazole (6.5 e) gave !-hydroxy-2-methylcjnchomeronic acid (t*"5 g, l*6%) , m"p. 236-238o d ç-it.153 zigo). -6 roni-c aciô (t) A soluiion of !-nethyl-la-phenyloxazole (4.8 g) ar:d- ma-leic a,-:Jey- d-rid.e (6 g) in ioluene (60 mf) containi-ng 1OO irg of hyd.roquj¡onee was boiJ-eo. rrnder refiux for f¿renty-four hourso the solution rvas cooled., íiitered., and. the solid. crystal-Iised. frorn water to give J-me+ÌryL-6- phenytcinchomeron-ic acid. (O.iu g, 5%) , m"p. 2o7-zloo çttt.159 2110). (Z) A solution of !-nethyl-[-phenyloxazole (4"8 g) a.'.d. ma-leic aC:y- c-rid.e (6 e) i-n d.ry benzene (60 nf) containing 1OO rng of hyclroquinone, vras heated- io /Oo arrd. irraciated. v¡i-th u.vo iieþt (:f OO8¡ f'or f ot'cy- eigfri hours. Tne solution r'/as coclei., trne benz,ene evaporated-, ar¡C- ihe resiåue crysia-llised f rom v¡ater to give l -roethyl-6'phenylcincho;ne ronic acid- (1 o e,76%), m.p. 213-2n,Do ç:rit.159 21f). Ër r'ìf t4 U H o -133- XIASS SffiCTR-À OF OL{ZOI,ES. A1I peaks greater tltan 5% of the base peak (arbiirar:-ly 10Ø) and- certain others of d-iagnostic val-ue are recorded. 'Z gLl) þ). ús 39 51 €,1 77 89 1Ø 16t+ 165 ¡oo Re1.Ab.(fi) 6 7 11 16 218780 +7 te ¡o/ 269 zg7(n) 298 R.et.Ab. (f) 6 23 100 L.+-t!. Z.l+-Dimethyloxazole ( J2l . 29 31 3B 39 ¿{-0 l+1 t+2 t+3 5Z i3 L ô ReL"trb.(/") 6 2-7 2 )+ + 40t+22 vs 51+ 55 )o 66 68 69 96 gz(m) ee ReI.Ab. (/á) 520 o z (zz^\ 2-l a1 -lfe thyl-) -tp,5 -d.ime )0 39 t+1 Ì+2 43 55 69 70 82 aer.ab. (/á) 16 22810 526 50226 \,))Q7 97 112(n) 113 Rer,Ab. (l) 13 12 100 12 / 2-t4.l-vyL-)+ oxazote- \i/).-_\ t2 /õ /^ 39 l+1 l+2 +) 22 bö o> /t) )t ¡ / neL"t\:o.(%) 25 20 35 I I ¡O 12 i0 9te 110 111 112 1u+ 125 138 152 15)(n) 15+ ::tel,;*o.(i?") 59 ¡UU 7 25 10 21 7?53 -131.- r-:D -<1ime IoxazoLe (Jg). ús 39 +1 1'2 \3 6g 70 110 111 1J8 Re1.Ab. (f) 10 19 /+0 86 +B 11 100 55 À. ts tr(n) 15t+ Rel..{b. (f) 13 2 -i-B 39 U tp +3 68 69 11o i11 tçJ6) 1r4 nel.m. (/á) 6 12 20 15 B 5 100 ',tO 91 2-i-3 utyl-5 -neth.yl-oxazole fl..!) " o/" 39 1+1 43 5l+ 55 82 96 97 12t+ 138 Rel.Ab. (lJ) 9 zo 26 1t 10932100176 ús tl9(n) 1Lo ReI.Ab.$á) 15 2 ut -dime 1e tt ús 39 41 ta 43 4+ rÐ 55 57 59 68 6g ReL.Lb.(ft) 25 6o 20 55 9 9 12 61 8 721 ts 70 11o 1U+ 138 470 4Ac ifi(n) 15t+ ReL.Lb.(ft) 7 16 t+ 100 10 6 173 1'-1"- ut:'f!-Z -d.ime loxazole (Lz-) . r? +1 53 57 67 6g 8+ 95 97 F.el-"-a.b. (l) 9 lo 7157116517 ts 1J8 159 tf(n) 1Dt+ neL"La"(/.) 10c o 102 -135- 5 -t-B utvl-2 .L'd.irneihvloxazole (¿,-3) . ts 1+2 43 55 ,o 6t 68 69 R.el.Ab. (f) 16 j+0 5 15 .)+Zt 22145 yo 97 98 1t6 138 tÍ] '¡.) þ)+ ReI.Ab" (f) 7 100 7 tr 16 91 2,5 t) tsne thyJ- -l'-phe nyroxzzole (5c). ús 39 l+2 1+3 50 51 63 77 78. 89 ReI.Ab. ffi) 9 6 176 13 11 21 18 10 y/s 10J 104 130 157 ttt rr.) 180 Re1.Ab. (f) 21 6z 76 100 B (lt 5-Ethvl-¿,-phenvloxazoLe ) " ús 39 51 61 77 78 89 90 91 103 10L ReI.Ab. (f) 781tç21 5 23 10 o 48 .1 à ts 1o5 115 116 117 118 .13O 1t+)+ 158 159 172 '7 ReI,Ab. (Í¿) 71?626 11 11 ¡UU 1t ús tT@) 17Ì+ P.eL.utc.(/í) 96 15 ) ç4 r omo-Zr! -d-ir:henvLoxezolc, (¡ L,) . ) '1tr ::J: 5o 2t 6z o) t) 76 77 78 BB o z ?,eL"Ih.(!l) t¿ 40 U 20 7 1oo I B )t .v: 9ö 105 tuo 11r+ 115 165 166 1gc 191 192 2 7 7t nel"al. (fl) l+ 46 ) ) 5 32733 ¿+ 193 271 273 zgg(n) 3AO 301(r,r) 3o2 Rei"!ic"(/o) 6 I I 27 5 26 ¿r .t zt 2J'Ie thyl--L,5-C,iphe n¡¡loxazole (¡ç), ts 5O 51 63 77 78 89 1o3 1o4 1Ø 163 Rel.Ab"(fl 5 'lI+ 10 2659 7 37 'î0 6 ts t6+ 165 ¡oo 206 2O7 231+ zt5(n) ú6 Rei"Ab. (fi) 9 B6 3t 17275 100 20 2-n-Pentvl--2,.5-Ai e (ç8) ús 39 +1 2t 55 o) 77 Bg 91 1o3 104 ReI.Ab.(l) 11 zl 13 15 10 59 11517 +1 ts 105 115 117 129 130 139 16+ 165 166 206 Rel.Ab, (fi) z9 7 a 6 12 l+ 61s15 6 ús 207 235 z)o 2+B z+9 262 291(n) 292 Rel.Ab. (fr) 2 100 18 6g z9 20 53 13 (59). 5 -E t h o-xv- 2 -ohe nvl o x¿z oLe y/s 50 51 63 77 89 1Ø 1C6 110 133 161 R.eI"Lb.(/") 822 7539 100 35 B 15 12 ús reg(m) 190 ReL.!-.o.(11) 162 ( 5 -E rhoxv- 2-methtrLoxazole 6O) " lt: 21 28 29 t+?- 1+3 U+ 5t+ 71 99 tzl(n) ¿ )¿ P,e3"ttb "(!f) z7 753381009728 t¿^ ¡ ¡ A^O ts I Zr) Re1",[b" (lQ 2 -137- aie ot 3 ts z7 28 29 t+1 \2 43 \4 rt5 6l 6B ZA Rel.Ab.(fi) )t z3 5o 23 60 44 2l+ t1 9 75 ts 6g 95 Yo 97 98 100 112 122 tzj 1u+ -10 ÀQ Rel.Äb. (fl 9 10 100 46 4- 13 7 21 I() ús 139 1tí 168 r6g(ln) 17o ReI".{b.(fl 12 1B t3 39 t+ H È,ê t-J N) a .t 2Q Compositi-on of some ions ín the mass sÞectr.a of oxazoles. Cornpoumi ts Composi-uion 2 r\ eJ -:kiphenyloxazof e ( Z) 269 tronr5*' 166 "1T'1o^ú a1 t JO' "11'9 Jar! imetinyloxazole (J1) C. -D 7o 4oHro 69 rfSo (86//") "4"f QØ") oÕ c4ir6N (gc/") cLH4c (tv") ÊÁ c-H-0)t 5l+ t¡"+o c 43 zEjo t,9 cz\,.N (lY/ò , ,n6 3sfá) (:Ø') c Fzo u c3!\ Ge¡¡ ci1+ (tq,á) (ll) 2 r4 15 {rin,eLhyloxazoLe 82 C-,=ÍJ{tö 70 r,on6o (gSí6) crn¡t (tiî) -139- Compound. te Composition 2 t 4 þ 4 rime ti-.Y1o:< azoi e 6g c, lIÂ0 Gv¡1 (Continued) ¿+J t,¡/ (te/,) 6B trrn6* 55 cJi-0)) l+2 ^útf¿+ QØù (zúi,) C-H.)o c fzo çtV") 43 "rn3o 2-n-Hexyl-þr!-d.ime-ultyJ.oxazoLe (34) 152 t9",r*no ]+t eq,) " rnjo 'ft w") þ-n-Hex¡'I -2 Ð -{.:;rnptinyLoxazo:e (lZ) i52 tgn,,,Io 138 c#r f,o 7o r,*n6o (lc¡¡ cre'to $%) cLHs[í Gø) 6y (Bq") ",fso ?q(,) "5tt9 .+nfl (tí') 6B cJ+ïí6N (gc,t) cSoo (f",r) c5He $%) -1J+0- Conpound ús Ccnposition (16) 1+3 c (gf1'") J-n-liexyL-2,[-d.imetbyloxazote rttro $%) " 3n7 2-Iúe thyl-l¡-phenyloxa zole (ta$) 131 C^H^rrï99 130 C^H+\>ö cÆ,0 118 Õo CJL O 11 t- ö2 $e¡¡ ñ ûnï \¿ öl^lrJ\ $e¡S 105 "l'0"^11 ^ c_rI,N (6e¡t) 1o¿r lo ^tf (+q() 103 CJí-Nt, 9trÐ "t'7l\ L1 $16) 90 ^u/o B9 c_ï_It ! -ì,,ie i hy1--J¡--phenyì-o xaz al.e (46) 131 (sV") "9r7o CÆJ $V') 130 C^TíJ\,ö c.H.0 1i8 oo 117 CÆ-+^[o! ttD) C-Ï-(2 0 AU 1 04- \J Õ()aÀI¡ 1141- Cornpound Conrposition ! -IIe thyl-[-phenyloxa zole (46) 103 c Qq") (Contánued.) di7 t/L* 3Ø) +j crHJo i+-¡{ethyI-5 -pheny}oxaz ole ( 4/) 131 tgnfl 1JO tgn# 118 c#eo Gq") c^iI_N 117 0( 105 CJ{-t, O 104 cÆ^Õu 103 cÆ_Õl 91 "î'7^v 90 ^rrlo ôÎJ- 89 t2 t+i ,ro3o (le¡¡ ,ft GeTs¡ I rl -D ÍmethyL-2-phenyloxazole ( L9) 130 C^H$ >t) 1ù5 c_li-O/, 104 CJT,N/o 103' t#z 6e,t¡ tå* GV") -1\2- Comoound ús C ornpcsition (J1) 1rt5 cir_No ! -E thyl-2¡--phenylox azol.e v( 1U+ .ron1 d! $516) c9ir6lTo @r¿) 131 c;ú.7o (Bú//") CtoHt 1 Qd/'") '110 tgnd 117 csr]?\ (eú,r) c;t, (tcÁ) 115 c aH7 Qq") .6rb* GØ") 't05 C-ILOt2 1 0À- c#e $Ø") .fen (ro¡¡ 103 cE, Glù tfSn (zØ) 91 ,ft 90 ,fe 89 c_ï- /, (5 CÆÄ BT ! -8 romo-[-phenyloxa zoLe Z) 197/195 Õb 165/170 ^L-t, Br -1t+j- Compound úc Cornposition J 3 r omo- Z-rne t hyl--þ-phenyl ox az oLe 211 /209 crnuN Br $t) fio/t6e C--ïI-/, Br 1 04- ./ter 0o¡¡ cge Uaíù 103 .f,b* GeÁ) .#z (+øtÐ (J6) 221 cr 2-Eihyl-4,!-d.iphenyLoxazole 6Hr5N 220 ct6rìt¿ QV") (¡c'0 'r''rgo 2A6 c,trt', ¿:s' 193. cr4Ht tN 117 ^ûuu 1Ø CJLO t2 104 cil-l'T l6 103 cJi-(Jl (lv') rf5* ße¡¡ 2-n-?ropyl-l¡r!-C.iphenyloxazofe (¡ 7) ú5 ct eHr f,o 207 tr¡Ht f 193 "..rr,f Qt",,Ð (Ef") 'rrjgo -i\4- Compound" ts Composition (¡8) ct 2-n-Peniyl-l.r!-d.iphenyloxazol" Z6Z #t gNo 235 cr eHr lî 2C6 cv*t Ð Þ b FrJ r,l -¿ L-l \tJ a .{1tr the calculatio¿"r of the theoreti-ca-l ratios for the losses ir,l4l{z't22t : }li-CHp' : },4-CID." : lr{-iD;r" in o.r" step processes was ma.d.e using +,he H¡çergeometric Distribr:t í.n.172 (;)T¡Û (Jj") D'(") (r./,Nr is the probability that r atons sample n viJ-J. be Prtr) r in a of deuterdll¡r-r" D is the nu.nber of ôeuterit¡n atoms, II tÌ:e nu¡nber of hyclrogen atons arroN = H +D. In attenpiing to match observed. arlc cal-culated. ratios by use of a transfer factor (t) [pgO] an expand.ed. form of the generai cord-i- tiona-l probabìJity equatio i73 ,,^t r:sedo r(.+s) p(r) " p(y/t) / .- \ P(AB)- is the probabilj-ty that both everrts A ard- B will occrlro P(A) is the probability that eveni A vrill cccu.ro p(y/l',) is the proba- biJ-ity thai event B wjl-l- occur provid-eð. À has occurred.o this expression is eqr^iva-ì-eni (with t" = 1) to tire Hyoergeornetric Distribuiion, but ha,s the aovaniage that a d-ifferent transfer factor (or isotope effect) .*t be appli-ed. to ihe rnovenent of successive hyd.rogen anò,/or d-euteriun atonis from a. posir-r]-atecl central reservoj-r to a car.bon aioxao tsl td H r¡ tsrì Fù I U) G -1t+6- 1 a Bud-zikiev¡ícz, Ho, Ðjerassi, C., Jackson, AnIf ., Ken:ner, G.'ÍI"r D and. chem Ner,',rnan, nT. r lVilson, J.I/Io , J " "S oc, , 1961+, 19+9" 2. Abrairaro, R.J.¡ a:rd. Bemstein, H.J., Can.J,Che¡n" , i961 , 39, 9Ø. ). 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S¡nnposium on Heterocyclic Chenr-istry, University of Sydney, '¡ -L'böo 4Ôtr. tL)e trfackroot, ï'I"C., l¡,rard-ley, 4., Curnuck2 P.J\n, Ollen, l{oi,", and Sherid-a-n, J", Chem"C ol¡rn'¿n. , 1966, 692" 126" Gignitti , Líu, ThccË=gh:-n,Acia u 't967, J , 38J" 4E:r 4t4l. a-7 Iful1il.cn, Iì.S. , J, chcrn oPh_ys. , 1955, ë., 18J3. 1?_8, Bloor, J.!., ancl B reer\, D.L., Âm chern , 1967, 89, 68J5. 4 oct D D l¡I Chem.Conrmrrn* avies, .W. r and- l,{ackrod-t, "C , , , 1967, 31þ. 1jo" Oesper, P*F., Lewis, G.L"¡ and. Smyth¡ CiP.e J.-¿Ln, chen"Soc o t l)ta2t fu, lt3o" 131 Bernstein, H.J.2 Popler J.4., ScÌ'neider, tr:f .G" rCàrr.JuChen" 1957 " , " 35 , 1t+87. 132" Bucicingham, AÐ., Schaefer, I"¡ ârld. Sch¡eid-er, i"i.G.r J3@-"?hT,:u¡ . 1960,^a^ 32-, 1227" 133" Borvie, J.iI", Grearn, G.Eo r a¡d' Laffer, l,{Jlo, Aust.J.Ohen" , i968, 21, 1799" ¿ zr | )+. Li.ínze, J", and- Ja-ffe, IIJI., J".Arn.chera"Soc-., 1962, fur 5W" 4 7Ê. Con.-forth, J",Y", iJr "ifeterocyclic Conpounds.tr (Ed-, R"C" nld-edie1d.,) Vol. 5 p32+, (Wif : i\Terv York 1 957 , "y ") 136" Karrer, P., a:rd Granacher , C., Iíel¡,..chi¡n"Act4, 1924, 7 , 763. 137 " Srodrick, Ao, ancl Peak, IioR", ref . 28, p/1 0. 4 7Q I )u ø Ref " 8J¡, p198" i39 " Yo'ang, P"Cot a:rd- R.obinson, R., J"chemoSocn, 1933, 275" 1)+O" Rosen'oa'¿n, J.J. ¡ âJlc1 Cass, \¡/,E., J"A m"chsn-r_,Soc. r 19.?+20 5lo, Z¡l-lr. 1U' Cass, ',,¡í,E. J"rLm"cher:"."So3., 191+2, 6l+, " , 7Ø " 1l+2" Le'iry, ì,[., ChenL"3er", 1888, 21 2 )21p" 1tr3 F"R", J"chein"Sgg. 1883, 11 " J"pp, , !1, " 1)la" Oesierz'eich, L{,, Che¡n"Be::., 1E97, 3A, 225}+" -155- 1)-5 " Fried.man, B .S. r Spa:rks, 1'1. r anci Äd.a¡ns, R. , J"Lrnochern.Soc t 1937, 59, 2262" IlrO¡ tister, J", and-Robi:rson, R., J"chen"Soc"t 1912t 9, 1297. 1+7 lfierovici, S", 1896, 2097" " @"BeI", Ð-, 4r Q TÐ I +J. lrbger, J., and. PhiJ.ippsof, O", . , 1925 , U, 65. 1+9 O¿, and. R.iJ-ey, R., Chem*Ber., 1915, 897" " Dj-eis, !8, 15o. Gonpper, R., and. L\hÌùe , H", Liebi-gs Ann. z'lJ2Yt ó'¿ot/ ^/ ó)eôt 151. R.ef. 8Ja, p116" l) Zc ?anj-, R., Bul1.Soc"chem"Fr"r l9+3, þ, 163" ¿,tr z and. D oki.. .\l Konöratreva, G. end Tluang, C.ÏI", DclC- r\l 1959,. z19t+O) .1959, LgL Ghee"tu!:.g , 53, " 157. -Fi-restcne, R.4., Harris, E.Eo, and. P.euter, Ï,I ., leiz'ehe.cron,. 1967, 2j, gL3" 4r Q Iie'r:rclon, î"C., and- Hal-l-, L.H" t letrù'eclron Let'c,, 1967, 3C95. .aÃo Konåratr eva G, Ya., Ìiuang, C "H., Dckl. :\l ltQ-, 593 ^ì.r^-vr¡vlllô^1vJ ^1--+Èut , 1962, t, 22O+), 160" ililey, RoIÌo¡ and- Borume O.I{., JoÄm"chen"Scc u2 1)l¡82 7A., ZOC5" ¿cl lOlo irfilef¡ R"H", Jocrq"Chem", 1947, 2, lr3" T Q^^ 162" Cornf orbhr Jo 1¡f , ¡ a.ad. Cornforth, R"Ii., V o ^r^^-VIIç-rreUvv O , 1949, 1028" 163" Yura, Yo, Report of Sanlqyo Co" Ltd., Chel]]"Àbstr., 1964, 61 , 12006. I OÇr Davj-d.son, Ð'", il/eiss, Ï1., anC. Jellings, L{"¡ J"or.q"Chem" , 1938, 2, 328" 165. Dornow, 4,, a-nd. Eíchholtz, H", Chen.Ber'" , 1953, 86, JBI+" 165. Lavlesson, So-0., Cronwdr-l-, Sn, and. Andersson, ld", Arkiv,i(erir.i" , 1961 , !, ú7 " 167" Overberger', C.G.¡ âT1d-Berenbaum, ¡f"8., {:!34!9[99:r 1952, k, 329) " T a^^ i68" Coraforth, JJf . r ârrd. Cornforth¡ R.Ho, I o ^r,.^-Ullu¡llrPVU o , 1953, gj" 169 ti,ri1ì-ia:ls, D.H" Rona¡rne, and- Bowie J oldn, J " r J., , "A,n"chera.Soc" , 1966, 88, L980. 170 lra¡rnel-is V llergenroihen, trV"i.: Ilærson, H.To and- " 2 "Jn¡ ¡ Val-icenti, J,À. J"or:g.Chein" , i964, 29, 123. 171 " Ileil , D.IÍ. Lessiie, I{.S., and. Tr-i-rner, 3"8", J.chern.Soc"o 1950 711 " 172" Kendall, l,{.C"¡ a^'td. Stuart, 4., I'Advanced- theory of Statistics." Vbl-. 1 , p133" (eriffin : Lond.on 1)6J") 173 R.t-r¡nshiskii ttEl-ernents " u L.7,oe in of Probability theory," (¡¿" (Pe:.ganon D"L:"G, îisha::t") p1la" Press : Cxford- 1965 ") 174" Krasnosirchek, À"?o, ÌGurel? nitsìcii, R.A, r Polyai ( 2 Õ Gra-ndberg, InIo, Z4"or.q"l,h-Lin. , 1968, 4, 'o89 Chen.Abstz' . e ¡ ^/)/OO t 69, 2jL6") Bowie, J. H., Donaghue, P. F., Rodda, H. J., Cooks, R. G., & Williams Dudley, H. (1968). The mass spectra of some alkyl and aryl oxazoles. Organic Mass Spectrometry, 1(1), 13-29. NOTE: This publication is included in the print copy of the thesis held in the University of Adelaide Library. It is also available online to authorised users at: https://doi.org/10.1002/oms.1210010104 Telrahedron Vol 24, pp.3965 10 3979. Pergamon P¡ess 1968 Printed in Great Britain ELECTRON IMPACT STUDIES-XXIXI THE C13H9 SKELETAL-REARRANGEMENT FRAGMENT IN THE MASS SPECTRA OF HETEROCYCLIC SYSTEMS CONTAINING DIPHENYL SUBSTITUENTS. A DEUTERIUM LABELLING STUDY J. H. Bown, P.F. DoNAGHun, H. J. Rooo¡r and B. K. SnrroNs Department of Organic Chemistry, The University of Adelaide, South Australia 5001 (Received in the UK 13 November 1967; acceþtedfor publicatíon L2 December 1967) Abstràct-The m/e 165 ion (C13He) has been noted in the mass spectra of a variety of heterocyclic systems containing two (or more) phenyl substituents. This skeletal-rearrangement fragment is most prominent in the spectra ofparticularly substituted oxazoles, imidazoles and thiazoles. Deuterium-labelling studies have allowed probable mechanistic formulations in the case of the 4,5-diphenylimidazoles, and the detection of two alternate rearrangement pathways in the spectrum of 2,4,5-triphenyloxazole. A com- parison is made between the formation oî mle 165 in the spectrum of stilbene and 9,10-dihydrophen- anthrene. DunrNc a study of the mass-spectral fragmentations of substituted imidazoles,2 it was observed that the spectra of 4,5-diphenylimidazoles exhibited pronounced skeletal-rearrangement fragments at mle 165 (C13Hi, high resolution). This ion is formed directly from the molecular ion, and its formation demands a Ph migration. Similar phenomena are observed3 in the spectra of the isomeric diphenyloxazoles, and tentative mechanisms have been proposed for the genesis of the rearrangement ion. The CrrH, ion is also observed in the spectra of 2,5-diphenyl-1,2,4-oxadiazole T¡.nr¡ L R¡Lnrrw esuNDANcE oF mle 165. Fn¡,cNrsNTs IN THE MAss spEcrRA oF DIIHENvL HETERocycLEs Abund. Abund. o1 mle o1 mle Compound Compound 165 165 (%) (%\ 4,5-Diphenylimidazole 42 2,4-Diphenylthiazole I 2-Isopropyl-4,5-diphenylimidazole 26 3,5-Diphenylisoxazole 4 2,4, 5-Triphenylimidazole 100 3,5-Diphenylpyrazole 7 4,5-Diphenyloxazole 75 3,4-Diphenylpyrazole 2l 2-Methyl-4,5-diphenyloxazole 86 2,5-Diphenylfurad 3 2-Ethy1-4,5-diphenyloxazole 100 5-Methyl-2,3-diphenylpyrrole 2 2- n-P entyl- 4,5 - diphenyl oxazole 't3 2,3-Diphenylthiophen 7 2,4,5-Triphenyloxazole 80 2,4-Diphenylthiophen 5 2,5-Diphenyloxazole 53 2,5-Diphenylthiophen 2 4,5-Diphenylthiazole 85 2-Chloro-5,6-d iphenylpyrazine 2 2-Amino-4,5-diphenylthiazole 45 3,6-Diphenylpyridazine 0 3965 3966 J. H. Bowtn, P. F. Do¡rcr¡ur, H. J. Roool and B. K. S¡uoNs (53/, of the base peak),4 4,5-diphenyl-2-pyrone (18%),t 3,4-diphenyl-4,5-epoxy-2- cyclopenten-l-one (21%)t diphenylmethane (29f),6 stilbene (30\)7 and 9,10-di- hydrophenanthrene (3O %).t As a knowledge of skeletal-reorganization processes in mass spectrometry is ex- tremely important,e it was decided to investigate (a) whether the presence of a promi------L ft IrÇIrr \:13119^ psaK rs onaraçrensrlc or all compouIrqs conlarnlng tne rn-L:ï-t" unit, and (b) to study the genesis of the rearrangement ion in the spectra of the 4,5- diphenyloxazoles, the 4,5-diphenylimidazoles, stilbene and 9,l0-dihydrophenan- threne, by deuteriumJabelling studies. This paper deals primarily with these problems. The relative abundances of the Cr.Hg fragments in the mass spectra of some heterocyclic compounds are summarized in Table 1. It can be clearly seen that the rearrangement fragment is pronounced in the spectra of 4,5-diphenyloxazoles (where in several cases it constitutes the base peak of the spectrum), 4,5-diphenylimidazoles, 4,5-diphenylthiazoles and 2,5-diphenyloxazoles. In the case of the S-membered heterocycles containing one heteroatom, and with adjacent Ph substituents, the rearrangement peak is less than l0/"of the base peak,* while the mle 165 peak is either small or absent in the spectra of the two 6-membered compounds. Therefore, a pronounced CtrH, peak is not characteristic of the Ph-C:C.ll Ph moiety, but is generally confined to S-mémbered heterocyclic systems containing two heteroatoms (normally in 1,3 positions), and to isolated instances, including diphenylmethane, stilbene and dihydrophenanthrene. *>* th\-* *l.o) *{o\o 1:R: Ph 3 2:R: D The mass spectra of 4,5-diphenyloxazole I and the two labelled derivatives 2 and 3 are recorded in Figs 1-3. It has been shown previously that hydrogens on aromatic rings become equivalent upon electron impactlo' 11 and that randomization does not occur for isolated hydrogen substituents attached to the oxazole nucleus.l2 This situation has also been apparent throughout this study, and consequently, even though the benzene rings are specifically labelled with deuterium, fragmentations involving loss of deuterium andlor hydrogen atoms from the benzene rings of 2 will occur in the ratio 3:2 (D:H) (ignoring possible isotope effects). In the spectrum (Fig. 1) of 4,5-diphenyloxazole l, mf e 165 may be formed by two pathways: viz. * The skeletal-tearrangement fragmênts observed in the mass spectra of isoxazoles, pyrazoles, 2,5- diphenyl-furan, -pyrrole and -thiophen, will be the subject ofa future publication. Electron impact studies-XXlX 3967 _(co + HcN ) -co -H' - HCN * (,¡) n rF 221('M*) ôl 00 càFb¡-ru ñ zc) %ryõr4 80 105 16s(þ) o 11¡ 193 z. l (D 60 Lrl t, 77 F 51 63 90 39 J r05 É[rJ 20 166(s) 80 100 120 140 160 180 220 E0/9 Frc- l. (CO * HCN) - * -c0 - HCN ,r -D' \ ,T 227(Mç'l (x) 199 o ! e- (2t 80 -H' ()TU 170 (*) z a o 171 z 80 f co I ¿0 93 lrJ 53 65 = 72 Jk lrl tlJ É. lr0 80 r00 1 0 r60 220 mle. FrG.2 3968 J. H. Bowre, P. F. DoNlcnuE, H. J. RoDDA and B. K. SIuoNs -co _ DCN * c^r-Lb t( Ði-N 222(M+',) c6Hsil.-oJt D -; (3) 194 e-- 165(Þ) Ltl O z. o 60 77 z. f co lr0 63 Lrl 39 105 166(q) t-- 20 139 J ÉLI-I 2 2 ¡n/9 FIc 3. (a) M-{CO + HCN}-H' and (b) M-CO-HCN-H' fappropriate metastable ibns (denoted by an asterisk in the Figs) substantiate all processes]. These processes are modified in the spectra of all the 2-substituted 4,5-diphenyloxazoles to M-ICO + RCNÌ-H. and M-CO-RCN-H.. When the energy of the electron beam is reduced to 10 eV, the process M + mf e 166 is always pronounced,withmle 165 being the minor component. Even though structures drawn for fragment ions are nominal only, it is argued that the most plausible structures for mf e 166 and 165, correspond to the fluorene radical ion (ø) and cation (b), respectively, although this does not preclude the possibility of more extensive rearrangement. I + a: mle 766 b: mle 165 The spectra (Figs 2 and 3) of the labelled compounds 2 and 3 show that the two Ph rings are involved in the formation of the fluorene cation [i.e. the processes M-CO-HCN-H' or M-CO-HCN-D. produce mle l7l or 170 respectively (Fig. 2)], and that the deuterium at C-2 in (3) is specifically lost in the initial process, and plays no part in the formation of the rearrangement ion. The latter observation negates the earlier mechanistic proposal3 for the formation of mle 165 from 4,5- diphenyloxazole, as this mechanism invokes the participation of the hydrogen at Electron impact studies-XXlX 3969 C-2 in the transformation. Nevertheless, the above observations still do not allow unequivocal proposals to be advanced for the mechanism. 4 5 6 H I RI Rl R2 R3 7 HPhPh I D PhPh 9HPh 10H Ph However, the spectra of the imidazoles 4-10 permits conclusions to be reached concerning the genesis of the ion å. The spectra (Figs 4 and 6) of 4,S-diphenylimidazole (4) and 2,4,5-triphenylimidazole (7) are different from that of 4,5-diphenyloxazole (1), as in these spectra, b (mle 165) is formed directly from the molecular ions (concerted losses of C2H3N2. and CrHtNr' respectively). Metastable ions substantiate these processes, which, although concerted, do not necessarily occur by one-step þro- cesses.13 The spectra (e.g. Fig. 6) of the N-d1 derivatives 5 and 8 show incorporation ,of deuterium into the rearrangement peaks, and after a calculation (which is approxi- mate because of M-1 and M-2 peaks) to allow for incomplete"labelling, a value of 50 + l0% is obtained for the incorporation of deuterium into the rearrangement ions (now mle 165,166 and 167). Such a value is much too high to be accounted for by randomizalion of the label, and a specific transfer process is indicated. It is of interest to note that the spectrum (Fig. 7) of 10 shows that the phenyl substituent at C-2 is not involved in the rearrangement process. I I 3970 J. H, Bowr¡, P. F. DoN¡,cHuB, H. J. Ronoe and B. K. Sruo¡ts I I ¡ t0 220!M*l - C2H¡NZ' ggo\o * Ltl (J (4) 219 z. É60 z. :) 16s(Þ) Q¿O 89 tU (M**) 63 77 39 =20J 166þ) ]rJ É. 60 120 140 180 n0/g Frc.4- - CZHDZNZ * N 226 (M*) 100 ) -c2H2DNi o * ñ80 DH zc) (6) 22/, o6C -2. f co 4 4j 92 ¡ t l_.r.l r69 ¡ 65 I 80 171 I êzo 53 (M**) 1 -J I Lri u. 60801 120 140 160 180 200 m/e Flc. 5. Electron impact studies-Xxlx 3971 ::hJo_, H - C6 H7N2 - CsH6DNi (7) x (8) - CgHT N2' 16s(Þ) t( r00 296(M*) loo 297(Ml ;- -C7H5N 165 -80 * 80 L¡l - HCN c) ,l( oã. oo 60 z. l 3¿o lr0 166 LU 7zo 20 J r93 t9¿ LU É. 280 m/e Frc.6. 165(Þ) r00 299 (M*) 0 CsH¿DgNi 0 - H x( TU (-) (10) â60 O z. B¿o 77 l! 89 =20L (M*) J Lu É. 100 120 t/,0 160 180 20 m/e Frc.7. 3972 J. H. Bowr¡, P. F. Do¡¡lcnu¡, ftr. J. Roooe and B. K. SIlroNs The spectra of the du-derivatives 6 and 9 demonstrate the participation of a second hydrogen-transfer process. The spectrum of 6 is illustrated in Fig. 5, and it should be noted that the ratios of mle L69:l7O:l7I are identical in the spectra of 6 and 9, although the relative abundances of the peaks are not the same in the two spectra. Two concerted eliminations are noted, viz. in Fig. 5, M-C2H2DNr' (to mle I7O) and M-CrHDzNz. (to mle f 69). The presence of the second process can only mean that a deuterium has migrated from a Ph ring to the imidazole ring in order to allow the loss of the second D atom in the rearrangement. This migration must of course involve both D and H atoms in the ratio 3:2.To explain this double hydrogen rearrangemsnt, Scheme 1 is proposed for the formation of b. Migration of a H atom to either nitrogen, produces d or e, which cannot be distinguished (we have a marginal preference for d because it forms symmetrical intermediates). The production of d (or e) provides an electron-deficient centre on one of the aromatic rings.to which the other may migrate (e.9. d --+ f).In order for the rearrangement to proceed, either hydrogen on nitrogen must migrate back to the "fluorene-centre". There is an equal probability of either hydrogen migrating, as/may be considered as a symmetrical intermediate, and although the acceptor-site of the rearrangement is not known, a possible formulation is g (it is possible that the imidazole ring may have opened by this stage), which may now readily fragment to the fluorene cation. SCHEME I + OR H c d e + + -(2HcN + Hl b a f Although this rationale is speculative, it explains the hydrogen rearrangements, and may be correlated with the ratios of mle 169:170:17l in the spectra of 6 and 9. A simple calculation assuming deuterium/hydrogen rearrangement to nitrogen iu the ratio 3:2, followed by s0ftback exchange of each atom (H or D) on nitrogen together with the possible eliminations to produce the rearrangement ions, gives a calculated ratioforthemle169,IT0andlTl peaksas I'O:2'l:1'2.Whenisotopiccorrections, Electron impact studies, XXIX 3913 and approximate corrections due to incomplete labelling are made, the observed ratios are 1'0:1'5:0'9. These ratios are not inconsistent when the approximations inherent in the calculations are considered, and also as possible isotopic effects have been ignored. If one argues by analogy, a similar mechanism could apply to the formation of b in the spectra of the 4,5-diphenyloxazoles and -thiazoles, although it is recognized that this double-hydrogen rearrangement could not occur in such cases. c6Ir. R2 R1 R2 13 Ph Ph 11 :R:H 12: R : D l4 DPh The formation of the fluorene cation (b) in the spectrum of 2,5-diphenyloxazole (11) has been noted previously,3 and a mechanism has been proposed for its formation. We wished to compare this rearrangement with that observed in the spectrum of 4,5-diphenyloxazole. The spectra of 11 and 12 are illustrated in Fig. 8, and it can be seen that the hydrogen at C-4 is not involved in the formation of b. Apart from the fact that Ph migration must occur, no concrete proposal can be presented for the mechanism, butit is noteworthy that theformation of b in the spectrum of 2,4-diphenyl- oxazole occurs only to the extent of 51.3 It has already been shown (uide supra) That the 2-phenyl group of 2,4,5-triphenylimidazole is not involved in the formation of b, l12l C6 coHs csHs 222!M*l (1r) 221 100 -; -(C0' HCN) -(C0*DcN) -H' * (x) trl (x) z. -c0 o 165(Þ) -co z. l -DCN m 1.0 89 [u 77 39 63 115 Jk UJ É. 80 100 't80 160 r80 200 220 m/e mle Frc. 8. tg74 J. H. Bowre, P. F. Dor¡,cnus, H' J. Ropol, and B. K' SllvIoNs but because of the pronounced rearrangement occurring in the spectrum of 2,5- diphenyloxazole, thè spectra (Fig. 9) of 2,4,5-triphenyloxazole (13) and 14 were exãmined. Fig. 9 shows the occurrence of two distinct processes, uiz. (a) the formation of b from the 4,5-Ph groups via the normal pathway (60%), and (b) formation of the C6 H5 (13) (14) - CsH2D3NO 297(M.) (M*) H5NO 100 x 165 -H'*) t( e, 165(b) H'(*) BO CgH5NO LU - (J ä( z -c0 -D 8) O t( -H'(*) z. LU 166(s) 169 =m lr0 + 40 LLI 269 212 F 2 20 J trl É. 160 180 290 300 160 180 260 280 300 m/e m/e Frc.9. d3-fluorene radical ion (mle 169) from the 2,5-phenyl substituents (40%\ This ion @le rcÐmay either lose a H atom (to mle 168) or a D atom (to mle I67).'When the energy of the electron beam is reduced to 10 eV, only two ions are observed in the mle 166 and 169 in the ratio 2:3. This implies that the formation ^lelSS-tlOregion;of the fluorene radical ion (ø) from the 2 and 5 Ph groups is more energetically favourable than its formation from the 4 and 5 Ph substituents. It is assumed that bond formation does not occur between the 2 and 4 Ph substituents, because of the r small relative abundance of b in the mass spectrum of 2,4-diphenyloxazole' The loss I oxazoles has i of carbon monoxide from the molecular ions of 2,4,5-trisubstituted been reported previously.l2 "'^I>.:.1f' H. R R1 R2 l5 HH 18:R: H t6 HD 19:R : D t1 DD Electron impact studies-XXlX 3975 Finally, it was of interest to examine the almost identical spectra of stilbene? and 9,lO-dihydrophenanthrene,s which both lose a Me radical from their molecular ions to form mle 165 (b,30% of the base peak). In order to examine this feature, 17 was required. The synthesis of this compound was approached by equilibration of desoxybenzoin with MeOD[.{a, then reduction with LAD followed by elimination of DrO. Unfortunately, the initial step gives only 65\ of the d, species, any further equilibration then results in deuteration of the aromatic system. As the final product contains only ca. 75% d2, compound 16 was used for this study. The partial spectra of the stilbenes 15 and 16 are illustrated in Fig. 10. The ratios of the 165/166 peaks c6H5- /H C6 /H (1s) (16) C=C -c6H5 H coHs 75eV 15eV 75eV 180(M*) 't81 (M.) 191(M.) 100 c -Me' * -80o ()[u ãao Õ z. l l¿0 165 (Þ) 166 Lu Jã,0 166 LrJ É. 160 180 180 m/e Frc. 10. in the spectrum of 16 are unchanged at 75,20,15 and 10 ev and each spectrum shows 34\ relative loss of cH2D. and 66 I or cllr.. This cannot be expdined by randomization of the hydrogen (or deuterium) on the olefinic link with the aromatit hydrogens, nor can it be explained by an intermediate of the type h, which would be the species obtained from an adaptation of the mechanism outlined in Scheme 1 (the participation of such an intermediate is unlikely in any case, as it has been demonstrated above that the heteroatoms play a significant part in the mechanism 3976 J. H. Bowln, P. F. Doxlonw, H. J. Roool and B. K. SuvroNs outlined in Scheme 1). Further rearrangement of h has been previously used to explain the loss of a methyl radical from the stilbene molecular ion.14 Although the mechanism tbr the loss of Me. from the stilbene molecular ion is not clear, it seems that at least + + h: mle I8l i: mle 184 two processes may be involved. The loss of a methyl radical from 9,10-dihydro- phenanthrene (1S) is even mofe difficult to explain. The spectrum (Fig. 11) of the dn-derivative (19) might be expected to exhibit loss of CD3' (see i). However, the (1e) D 15eV 25eY 75N 184(lvf) 184(Ml 18¿(M*) s -80 LtJ ()z É60 z. f CD<4U r---x10 ul I I I 168 ã20J I ul I É. I 160 180 160 180 m/e Frc. 11. Electron impact studies-XXlX , 3977 loss of cD.' is minor, the major losses being cH2D. and cD2H.. Again, the mle 166, 167, 168, 169 ratio is not markedly affected by decreasing the ørergy of the electron beam (see Fig. 11), and it appears that little randomization of deuterium occurs. In a previous papers it was assumed that hydrogen lost in the M-H, process [to produce the phenanthrene molecular ion (mle tiï)] originated fromlire 9,10 positions of 9,lO-dihydrophenanthrene. This is not the caìe, as the major loss in ihe spectrum of 19 is H, and not Dr, and probably indicates considerable rearrangement of the molecular ion. Although the losse: of Me. from stilbene and- 9,10-dihydro- ph-enânthrene are complex, there is little doubt that the formation of b proceeds differently in these cases than it does for 4,5-diphenylimidazole. These studies demonstrate yet again that extreme caution must be exercised when postulating mass-spectrometric mechanisms without the aid of the spectra of suitably labelled derivatives. EXPERIMENTAL All mass spectra were determined with an Hitachi Perkin-Elmer RMU 6D double focussing mass spectrometer operating aT 75 eY (unless otherwise specified) with a source temp of approximateiy 150" and an inlet temp between 50" and 200'. All samples'used in this study were routinely checked for purity by nuclear nagnetic resonance and mass spectrometry. 4,5-Diphenylimidazole, 2-isopropyl-4,5-diphenylimidazole and 2,5-diphenyloxazole were purified pyrazole,23 3,4-diphenylpyr azole,za 2,5-diphenylfur py r r ole,21 2,3 - diphenylthiophen, 2 I 2,4-diphenylthiop pyrazine,3o and 3,6-diphenylpyridazine.3l The spectra of 5 and 8 were obtained by introducing 4 and 7 into the source with deuterium oxide.r2 Labelled compounils 2,4,6-dr-Benzaldehyde.Prepared trom2,4,6-d3-aniline by the method of williams ¿¡ ø/.11 2,4,6'd'r-Benzoylchloriile. Prepared in ouantitative yield by oxidation of 2,4,6-dr-benzaldehyde with KMnOoaq, followed by treatment of 2,4,6-dr-benzoic acid with SOClr. 2'4'6,2',4',6'-d6-Benzoin. Prepared Ítom2,4,6-d3-benzaldehyde by the benzoin condensation. 2'4'6'2',4',6'-d'6-Benzil. Prepared in quantitative yield by HNo3 oxidation of 2,4,6,2,,4,,6'-du-benzoin. (ds : 4%, d6 :96%). 2-d-4,5-Diphenyloxazole (3). 4,S-Diphenyloxazole (0.58 g) in dry ether (10 cc) was added to a soln of n-Buli (0'036 g) (0 ffrom Li and n-BuBr 69 g)] in dry ether (20 cc) at -65', under dry Or-free nitrogen. After stirring for 30 min, DrO (5 cc) was added, the ethereal soln was separated, dried (NarSOo) ãnd evaporated. The product was purified by preparative VPC (30% 5830, 12). The NMR spectrum lacked the singlet at 2.19 t indicative of the 2-H of 4,5-diphenyl oxazole.2o 4'5-Di(2,4ß-ü-phenyl)oxazole (2). Prepared from du-benzoin by the method of rheilig.ls purified by preparative VPC (see above) b.þ. 190-194.114 mnlJg 2-(2,4,6-dr-Phenyl)4,5-diphenyloxazote (14\. 2,4,6-ilr-Benzoylchloride (1.3 g) anct benzoin (2.1 g) were warmed on a water bath for I hr. The benzoin-d.-benzoate was cyclized to 14 by the method ofDavidson et al.rl The product crude was chiomatographed over alumina in ether, and crystallized from EtOH as colourlesq prisms, m.p. I 15-116". 4-Btomo-2,5-diphenyloxazole. To a soln of 2,5-diphenyloxazole (4'4 g) in glacial AoOH (100 cc), boiling under reflux, was added a soln of Bt2(3'2 g) in {oOH (15 cc) over a period of t hr. The rhixture was cooled and a solid ppt removed. The filtrate was poured onto ice (800 g), extracted with ether (3 x 100 cc), and the combined extracts washed with Narco.aq, water, and then dried (Narsoj. Removal of the ether left a solid which was chromatographe{ over alumina in light petroleum:ether (92:g) to give G 3978 J. H. BowIE, P. F. DoNlcnun, H. J. Roooe and B. K. Sltrlol'¡s 4-bromo-2,5-diphenyloxazole (1'1 g, 31 /.), which crystallized from light petroleum as colourless needles, m.p.70-?1'. (Found: C,60'2; H,3'5;N,4'6; Br,26'3' Cr5HloBr requires: C' 60'5; H' 3'4;N, 4"1 ;Br' ZS.Artr¡. thc NMR spectrum lacks the singlet at 2.68 r attributed to the 4-H of the oxazole system.20 3-d"r-2,5-Diphenyloxazole (12). To 4-bromo-2,5-diphenyloxazole (0'3 g) in dry ether (10 cc) was added (20 cc), for t hr, decomposed with soln oi n-Buli ffrom Li (0.07 g) and n-BuBr (0.68 g)] in ether at -65', D2O (4 ml) and worked up as for 3. The product (0'2 g) was purified by sublimation, followed by prep- - 1^^1.^Å +t^ aiñûlêf afatlve vru (see aDoveJ, m.p. tL-t) Ille lìrvrà ùpçvrruru vvuryrvrv¡J^^--1^+^l-, v¡rqr*vlvr¡vr¡v^L--ô.+-r;or.i^ v¡¡¡Þ¡Ye at2'68 r in the spectrum of2,5-diphenyloxazole.2o ,/ 4,5-Di(2,4,6-dt)phenylimiilazole (6). Prepared from d6-benzil, formaldehyde and formamide (cf' Ref' 15) Crystallized from aqueous EtOH as colourless needles, m.p- 232-233"' yreld 6l/.' )-phenyt-4,5-di(2,4,6-dr)phenylimiiløzole (9). Prepared from d6-benzi1, benzaldehyde and formamide (cf. Ref. 15). Crystallized from aqueous EtOH as colourless needles, m.p 27V272"' yield 601. 2-(2,4,6-,ü)Phenyl-4,5-itiphenylimülazole (10). Prepared from benzil, 2,4,6,-dr-benzaldehyde and for- mamide as for 9, m.p.273-274". dr-Stilbene (16). Reduction of desoxybenzoin with LAD gave l-drl,2-diphenylethanol, which was dehydrated in DMSO to give dr-stilbenei m.p. 12+125" (cf. Ref. 33). This was purified by preparative VPC. The NMR spectrum indicated quantitative incorporation of D (>99% d) 9,10-dr-9,10-Dtileuterophenanthrene(19). Reduction ofthe dirnethyl ester o[diphenic acid with LAD gave 2,2;-(d"-hydroxymeihyl¡diphenyl, which was converted to 19 by the method of Hall ¿¿ ¿1.34 Purifî- ãation by.pìeparative VPC gave 19, b.p 174"117 mmHg. The NMR spectrum indicated quantitative incorporation ofD (>99 I da). Acknowledgemerrús-One ol us (P.F D.) gratefully acknowledges the award of a Commonwealth Post Graduate Award. The Hitachi Perkin-Elmer RMU 6D mass spectrometer was purchased with the aid of a grant from the Australian Research Grants Committee. REFERENCES 1 paft XXVIII J. H. Bowie, R. A. Eade and J. C. Eanl, AusftøL J. 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