m r w if w iD Awmxmmtmmmn, m m et rm m m m * aku A U ^ ^ m o m m v twtmmvm W Da $&a@ m A T IM 1 S SobsalttM 1m» tli# of Qmtoati&m 8fcn4 t«« of Michigan 8t *&* Coll#g* of Aa*ie&2tttr« &»$ Ap$lt*4 Stalosteo in psiftiml £telfillsu»tfc of ttt* rem its for %h# 4 «g*«» of OGCTO& 0?' 'dapftrtflMls of CtumUrfeiy IfS l ProQuest Number: 10008425 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10008425 Published by ProQuest LLC (2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. 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T ill 1 *0 A W W » 4? w o A JiE 0X X -A «S 0S T !3m »ja*fl.'F ^8A i!C >te rif80OC8tO8S9R8*« 80 is m w » a * m ,t m op i*r aw*wrb»iw $m HMtwMrnmm m m tM a *n ,rm u m u ntam m tm tm s . . . . . . . . . . . . . . . . . . . . . . . si x M a c w x u s h w p s s w w Asm T B rn A iJ o K s .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 a SHB06W tm vm & OF 1,8 ACgT«AWWSWSTO- ATI AXXOXT* A o s r m w c f o r a s w i^ s w ttT J in iA g o is s .. .. .... . . . . . . . . . . . . . . . . . . 88 u e r o? n m m m 1* $U H in $y£rtth@ais*** AltfaKtgh t«bm#©t© its e lf dees not *ppmr to to ©hermetertsed by *sy ?&ernnaeologi m l not loo# the in&nsdtaetlen of agtMritltttsafee Into the I nnd © position* of the ring ehmotors lapfcrfc* d efin ite mod to many Inetsaees ve*y pmfeiind motion© to the resulting eompsnn^o* As satiMML by arose «sd ^enthereteue m the result of m eosnprsfasnsiv* ©tody of 18© tstr a ssls derivative*# the ^mimootegtoal motion© of these ®tmpmw£® gonormtly tw elve the eentrel mrvm® system* the aobsbesaesB exhibit sbim tebeiy or depressant notions m well m vm pim degrees of edited etlmtlnbsty mod d«prass«nb ©cbiem* iM hst «M eo^wer&ore ( 8 ) Imre synthesised n series of nitre- and ns&nopheupl tsfemtolo derivative©* It m© Interesting to observe that th® Introdootioe of & ^«eaimo|ti^rl group at either the 1 or $ position o f th e te tm a o le n n e lm e re s u lte d I & ©empeunde hm viee p H m r lly d e p re s s mn% motion* fh%* else synthesised severe! l«^*tho^t^e?3yl*S«»mll^rI«- tehraseles {?)* The present# of * group esumed a imr depressant offset (7)» It Is the psrpMS of this iwesbffptlon to flgpnnd the knowledge of the relmtlenshlp between sheet sal oonefeitetion eng jdmrmoologlenl properties in the tetmeole *srts*« for this purpose# I t nppeered to be deeimfcle to study the #r#fm*mtle» of n series of substituted phenyl aibyl tetmsoles in shlsh both an, nlte^r mad an salno group were in* eluded ms substltoonhcs In different positions on the phersyl ring* sxssresxcAJ. mm m m m fh» ftrot mm in 16119 W Swedish tfeondtft <$# A* MlMin ( 9 ) 1dm 4bft«fv*di tfaAfe tfe# action of *#14 m &i~ *p*na$h*8igrIfeyAm ntm 1 «A tn th® f«ra&tcm of a aow^onsttt ho n».«r£M ^ f«rm ln ^i?^(€W)(Cl^)* %&a^lyai$, follow*! lay do* o^oaylatloa* gmtn««6 m 'touring fch® f e w k c^h-^i tho trnlt, rwMtlnod ln%*ofc throughout th® tftrafom ttn n ( 9 >* Blaltn ( 10 ) H i* wm® t * ! # * * * ! * f o r t l w m m r i n g s tm e liw m * iPOg - * c^w $ ** ?! 3f fm 1899* §1*4 la ( 11 ) ti«e««ddl In gn»«p&iiing t*fcv***l* lt* * lf fey %hm f n l M t a g » « * !« * o f fr n fc to n * # 0 Eg*i * £*m ' ?! ti B M lsi& rtl* CJL<& * W 300H * ® i Sf „ $ mft*CgH *3f * CaCOOK isitmtion * , f u 1 *W ' UWL • 0 h -h 4 , 1 * c*eooar xr )( f sw? * e*H oB lA nteltm m& 4 mtkrtgwyl*t Im ) n I $ *r fortet*** tm 1906 (IS) syss&houigod X*hyd-r«ay*6-^*B/lt*bttuii>lo bgr ln to m o fe io n o f to*ns*tty&r*sc*w y 1 o to lo jrid * o o d lm a s ila * ?? I*0M M * 0 -*» I 110 - S\ $ H roduofcIon At ofemtt the &mm time* OOhreofeor (13*14) jmoeeo&od\ in « • 6 -S * I II H 1 55 H0 i (I 0 M A ^ W ^ w ® ’ filfe # * > m%m' II 0 d*M? * 6wH! l II b mt S M U itt M 4 (17) AooorftfeoA fim mwrnvmMp oimplo wothod for tbo fioororotoir «f leotoBdJi tafeo l#fi dioobotltuhod to&soaotoo* With om ©qoiwaloiit of hydraaoio aotd* hho gwodaot wot *o amid©# ?oo or m m oqiiioolaw&t of hydro*©!© wold tod to %•© fowfcfoft of tofef**elo* along i -lAiitfc -ttfittft-jftoBiM BnOTjI dfeOBfittfe mfefoOfrt* 'BBOMMilliftA&il&dl,*. 1 1 ) mo 11% — * *«c ♦ m ii I » H or l '* * a-noc * im ii ii t v Nr fho MMliORiiotA off«r*d % SoholAt to ooptata tho rme&im of hydro* •of* ooid in tho $0000000 of dot4 ottolfoto oioomod tho formation of fin ioOsio radical {>$$!) wttioh im ^o^oatly rooofeod with tho hofco&o to giro nrn dotsao* Tfe© tofcMlolo f&rmt-tm mm mplmimtsd W tho tutor#* ootfofi of » oooimd ami# of hydro*oto field with th© tmim or ®om« ©fchor toNrofifilfit# formed hy roosmBgomanfc of tho mim»* ilpieimm oad d&otlo ( 1&)# homrort orltleisod Setaal&fc* $ mw&mnim asid ooml&dod that siotthor hho Mtoo raditfil nor t&o m%m» mm itowtrod in tho reaction h&mmm hermit and hydrogel© odd* later# Mfth ( 10 ) devwfagmd a m m ooo^t#» Ohio toterfNM&afttea ood tittonmood m oautooim Ion woehejtimi for the feraotten of tefeiMeteo in the OeMdt reaction* l# 4 l* m m B rn m and S to d frlth (8 0 ) li^ f t y r M (H I W tfe* tsatde £ehrsM0fe«rf ® p ro e a d u r* with hydmseto «,eid % ® . h m % w M n r entoratofm totntlea* l%m# Ime«tl$&t©r0 tm®& $tsafc map twid© ©hlarlde# which mmM wfc react mttli mullum ««14* yielded b*fcra*©l« dsrtetfcivefc if *eM m % M m mm «**&* tbm ntbsn mahetitetat mmmrntn laid# okirnHMm nhlth wtim vM&* t w i i imdtet aside o«M %+ a#ar*rt«d into tetfaim it# by lil# tM tittttt** starting #«*13tayS ar $*a*yl th e y SKt*©##d*dt in g re yftri& tg & s a ris # I* S d ia iy t * and V ssiseesfir© rm&teim wlIM gbrntfkmm P»s*fe** ehierid© mm hf&mml® acid* n'tcxim m i «»#eMi *% el &*«c * % * fh# ttrs&fttag ta p -m t ©£ reseti©## m fMtlgJli (SO) m lf t s imi Ii 1 s j? Ni?* applied fcy rets imun m& «£*l©ridmi In #*t©h t* wm a«M*atl© and 1 m s titte r nllflxntl# #s? tn M llit fhm rtsttieb itn t* in&M® mtmri&m &*» flttd rraa bttsesaldist mi# t^H lasht by sad (S i) t* b# totted an m rllm wsife by w a Wrsassa. #33# M# ©e«^Fk#re (Si«S$#34) In iM th It mm 0mm that MUt* «&l*ridtes ©f alipbatl© M u th e r e t * m u t l it e t p » © r m -* llg lM & le p t t f # n i the ty$t morn c h n m e t^ ria e d by tilth reattirity that ttagr mmt€ m t b# im t&twl* In S3HB&* Ketfett and «t*et»to«r» (SI) 4pa&h*tiftt& a grmip af twenty** *1* | #| d&jttfeafcttoifctd thrttftititft and &«KN>&*tmt#d that the prspMfttfcltn ©f tsb etsaiet ;£**©» IM^bfctlbtttd ta ld ti by «©wereIon la te isa®4 ® ehXarld## and ifa&arftttitn ©f th® la tte r with hydra*©!© ©©id m© ©u*i booaftwi&oa m inelio&feod fey iron i w lim it s md MWtgRi ($9 ) fewfc oml& few *tp&l«d maoeotafwlly to & groat ta ri «ty of awfetfeitntod «s»i4ot Isetoitng «osi^lo%o$y nltgKuttlg typp®* fho stab ility of tho lmi msoomwtwt in w Sftm&tft ommwAsor* to th# of a mrtot'sy of nt%m$i®w%i&4km* **1*0 fw*» both m ami iMtoyl oltoraw&lifMMU fh®y tbs Into th* eormgwnAtng nwAnoofeonyl** totgfesel** fey wfeojytt* feylmgwKtion# «&* * rooitlt of tfeolr &M Fe*tfe*r*fco*M» (1*0$ 0#4»$) bar* 4mm oortnim ©onolaolom roi&nting th# rotftttoafltiip feo* twwas ©feomio&t *tmMJt**r» m i tortrottr©®* *ofe|*it of tfeo t^ m oolo In % ««sHto* of 1 #.S ti*mb®Mtw%os! tofcaoiw&w# in mbl«h tfea owfeotitwoat* wor* hy€rooas%om r&iioaXt* tlwgr oonOtwAwf that © «tm l mmrmi otiwolotion m s f«*w**0 fey * %*oXoatl$ti&tio grmp in th* % pmi%im or fey ltt*r«**i*g tfe* otto of a ®i«plo alkyl group in tho ®sm*o pMittott* On tfeo ofefetr HaM* £o|MF«ft4m& notion mao fororod fey i mmm# ton th« otto of m alkyl g w sf OafegtttatoA tm position @« tb® Intro* 4u*tt** of a ftonottoiMdt grwo^ omob at mr nata® grtmp at a toanal to few a Awfetfm&niftg faotor* ifesm tha aalm gmsp m&® attach®! dtroofely to th# t«tm roi# ring. in ftalfeimi §# eompotifid* with *utr«ty tftiiitli&ory notion roowlt#!* I3h*a ®m or two carbon atow war# itstt?rpooo^ wOn* feeteieea the & m p m iI th e i M m t t ring# e t i i l in p e titio n s, a d b te d t o M m r e m it # ! * ih ® d % r# t o f is U m t& tim i n r &#pro®«i«m b e in g n o tifie d % thft mto&tm- & f other mhfttttftessbe in p m ttlm t» Ta&erpee* lug ft «yoii® eyefcee %%&mm the ma&m group md the t^fcm*©!© ring m*dm®& th© M a ttin g ®wi®mMM w ith e degmfteesft eetten# The ftotless we* mere pewdy deprmftftBt when the *j&«e$iiaiorX gmnp mm ®hlft®d fnw position $ to peettteift l« The appeared to be swdemtely effeetfcre ee eedafttir* end lumlgeet® egonhe* Msoeler* *§hag# Fm%h#r#h®n» end dree* CtB) &Xm iweetifftt^d bh© aheorpfciei* epeehrft of * eerie® of ttdrty"«esift te b m e le derlrwfeieee end th e ir peeetble elgt^fioftj*®® in re la tio n to the ftaiwimoologloftl action o f th e # # e o a p ftM tft* th e y feeed th a t th e wftjerlhy o f th e e n rre ® p ro * eenfted km ftftadae* ©me tow&ri the h l# e r were length® # d«ei®s»ted &e M. # J& end one temrd the i«var iser® iwftgtMr* deeigmted aft TMy eoaeleded that* eltheoh ereeptloe* m&mtimmm eefteeeeiag ft faatewt end purely ottm * latteg *ehi«* ehewI l i t t l e er ae ftbeorffcioti in the entlr© n itre rielefc regies* end without b§r the rftft&e e f the ^eelmmtL epftofcrephobosietor* Atee> ®K©ep&t©n* eofeetiiiieee pseoeesing ft potent# purely d«prft#*m n& notion efthlMteft & ms%e& B peek* Ufte het#& of the b p o# (Ae®8t*dft&R/*) me pvwfMirtteaftl to the jdteeay* Ae any appreciable absorption in the ultra vle&efc eeeorred only dim mh&tltnmk® mumble of appro©i«* able%®»eiiftftfte mn$tt$ftbi®sf* wttfo th« tetreeele »y»t«B* wore preessat* %h«sy te n ttttiirtly oe&elndoi % et fo r the te tre e e ie d*M *fttlr«e» Mae eob* etltu h io e of grmp® a t peelt ion 1 et* S en the t©trft«ol© moleuft eefMtble of ft h i# degree o f "xeemsftee oo^1op£tioi5n eeald bo conduci-sr® to the product ion of a m&mr&ml p w e o s si^ oentrel dopr^smnt proportiee* e7»» The omatmtm* of these aothoro are &pm to t o c r it is l^ that a lirait©a m w fom o f eim&ples? w ore adU tafeei frw n a la r g e g ro u p o f m a n te s whose #arw aool#gloal actions bad bom. studied# n o t t o ineatwd© m m r p lm i n o tiiife a %l$h Apparm tly mr® vm& zeroised ®£ © o r ^ g a tlo ii* oooM bo aotlolpfeto. ohon. the giharoae&legi oat aoklot* was yriwarily »tiw * la t o r y * %n ife to w otfe* t o o r to * o f ollM W y ^ t m n o lm h m hm m O^afehooiioS for %h® porpm® o f Sotioraiolsag thm offoofe of .vuyiae the p lo t of i&too&fMt of to tt t&« &t$«r the oatae groap to- iho pbooyl msoloo# 3pm t&« ^om &oolofiool i&ottos® of tho om pm wlo* fh# opeolfie oo&pii®4« ohmm mm bo oto i§ift #4 1* fir# gampu fb® ooilootiosi of bho $rm p$ n n to ttS 3p»m i&o ^ w m o o leg io o l & i k m m &mlmpb®®ylm &md m # & h m & 0 o p ^lb ® km $ o i® im & m b lw m « M tt*@ o w ilik M lit F of popm tlos* of th * rrn gkin lb® or &« m m iis&ormo&imto®* X 1 *{ $* )« * 8 * o llry it ofern g o l m ffe o OOO^Nm$$SO i l l grOOf^ % O695^boB30d' 33 OSitSSO gVM Ip 33d. & oiwtttlicpy grmif mro> to tto t*fe«**tfto ring* && ®rmo *a& fofcthorototto {$#?) hm® n h o m t h a t $t&» fo fe o tlto tto o o f & o to g lo M ^ l o o f ^ w ^ o r & o im g to P^otlMprtltappl grwop o* tt»o pftiMe&o ritsg oonooO tho roswtHog ec®*. pood* to %o oootff&t merrooa ioproaoooto* i t » (kotioo of bobh thangpt tfeot tho tfeo oialsto o&d tfco m bhm y group into tbo oosso $hpr$> oooloam n&g£t looS to m oM ib lv® off act.» Tho oBsyt g*m*p oafeotttotod to tho 0 fMNiitloo mo-tftrloO £#m owsthrl to ofekylg. propyl &M ioopefgrl to orior to oto% tho offoot of OtSfcitl* bh® loiagth oM tho byHMditog of tt*o m n* w w m $0 et * <# t n J n U ft# #*% i i ttw m ** < y y t #©}* in g?wp 11 md fcfc©#« in g iw t 1 mi# tii# 4i#9fa«NMMfe #£ tti# 1mtehmp grmtp &"r#m the m m position t o on# o f th # 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