THE PREPARATION OF THE THIENOBENZO (B) THIOPHENES AND THE SYNTHESIS OF SOME W-(N, N-DIALKYLAMINO) ALKYL NAPHTHYL SULFIDES Thesis {or H19 Degree of M. S. MICHEGAN STATE UNIVERSITY Eciward Paul Dunigan 1961 THESIS 02/ f‘WW‘r .v. i )5». ..‘-“' (71- q‘.\... 1.. L." U {UV cmty V—V _'. .3“ ”Y . .r\. O J H' k; . :.;- H‘T'W: ". m 1".” ’ an“? “xv: " 'r I 17 ,' "wisél .R‘ITIJ‘l‘I J.-LV.J. .l.~.é"-J.--\/;- UJ. 1 I Ll-_L Iohk/JJ.JJI;J\/ . ;‘. x)- AHJJ-JJQ "J {’11 ‘1 fr "‘7' '{1‘ ‘ ‘ To (1.? (' of '1‘ $11. *‘ -J . -.--. .... .4- ,LL) '1. L4\./.'.dJ 1' «v ‘w': 1' ‘r' ‘1'";- ,' ' ~—. *v f-v :1 1,"",' (‘i T'V‘T‘I" .‘\(". .:\ . v “LI H ' .‘ (, V ,-_ J,.]..a‘.4 -. A ‘ ‘, ‘ ;. ~ .! l,~‘JJ_d- ll — JI—t‘ ~b oAiukg’ A~J ;..1. .‘Ah- o-J-‘hfiJ—J 3)?» A-Jl‘ll)- bl ) Y“_ .. .LJ y-‘u an —\‘ «‘l ~v-r vv‘v" ' " ‘ -‘. J | '1“ r ;‘ n I v _ , l"- -.-CLJ 1.. .LJ 'J\/.\-_. a:-; 1‘7 “""\f'1“ n;'~ qfl ‘ {'1 '1’ ”C‘ ‘ 1 .JR‘ - ' I: L, x J -.' 4L4)». J._ ‘1 . KLL‘ h. .L: Ahuig) I {7‘ 11"“ ; .L. .1- ' ,3 .L. - mud: “2.9 «26% yo "" 7 ' ".I- J- 'I ' - '4. ,. -. 4“ rlsr‘ \. 9 _ w w -J no r I'.-LC11].£)C;; k.J{J\AIxIO LJlL]. JCJ'. U]. U‘/ .. fullelment n -1 '1 “ lor Lad he”. “‘90 "I/gm-'v \ ) " '. ‘ ,1 .- 1-4;LU LJ-‘AL .4 (:- kl A. "S D K; 1 J L J— v. LIL‘ \JJ. at of Che: fi 7 Oi tne ree of reouirenents * n ’r‘t‘fi' T m - .7, .\ ' u “A. U 1 L istry .fi‘ ._-2- V ,- i x. 1 ‘..- . -2». - .. ‘LJLELL. \A‘Q‘x -JV ‘ne 1 1A.: 13:3'32’1 C11 If: _ _'_ x ) 4'-.r‘lO \ ' 9 O u , I r] . a , 1» .,“_. c . A.‘ t x“ ,_ A2 ‘ W .“‘ 2 2 ‘7 : .,» 4- _ h 7‘ —- ‘fi ‘7' n .- 1..- - j;- ~ ~ +— \ (- JV... bk. 0 .1. l2 gu‘i M. . u. 1, .._- L2.i My. 0;. h." \,-IL.,-H€L2_‘.._.C . \. MwC.) ' V \ ‘ o ‘ 0 Q .4 ~ . - '5 - 1" x" -~ .~ - >' -~ A 3- ‘ x r~ .- - A -v- .- ~ \ -\ (‘ ~'\ .A 0 r‘ v.4- '.‘. (‘1 " .\ "—‘ « J , A , 4 2. , _V _ . . .‘ 2- ‘ . A . klO \J-o- 4 K’ALAVxltkc K."-» ‘4\J'€'~J‘ \J le‘ Anvl-\.- J-‘-JO1-l\4-L L.) L‘--‘- Llaac \ 5’)“- ‘3 In._’-- .. 1. 1 a. ‘ . ‘i f—!- q "' ' ' ' " “ ‘v ' "‘ " T' :71 . .""- *z'. 3‘ r‘ ' "' “.' 2‘7‘ .' "" “ A .' .", ‘ D:- u -- 0:1...an L - uxwwl 5:]_-.,1..-\.L.l_‘..-_IJ\_'\-‘-1_LJL‘L\-K/“AA \r-‘.._.;.'.J/ L --.'. f4. rt“ Ts n+1va-I (5‘ 1 ‘ LL——LroAUA 1.4.- t_: . . L30 J ‘ . . r11” ,3 ,- “V. ‘7'- :nr, ._ I.“ .3- ‘..: 7‘ (N .1, . .7 ‘N 1 ,r..'-.,‘ V- .r',‘ . 'v‘“(‘.1"“’,2 7,, , . .L .L\.J t;‘Aa.~b$A\/~)\J “O‘wa L14.- ~ \ -lC _1_\2/\J-ul’ ,. -I'\,.. s: - \-'1k-.- ‘ v. . -2. I (‘1‘ ho“ V.-- .‘ ‘ wr ' —\ 1r ' "‘u ' A d - Tr. Ar '.,- ‘ w - . . 2 '. 7?. 1'1.;r- " " T‘ . a‘H- ‘ "1f: ‘ ’r ‘ V'Ak. QL_‘.v.ka.L..~jr O; - -.. -.LVA.\JV-L.C - 2)~«-\, #0.“...Ovv'4ou U.-C, J.._..o\./- 0C4» . . . fl ' ' 7,- . . -'- , - -' ~ - ‘.> ' .LA ‘\ : :— - - ~ “ _ ,. -,,-. -'- , . - a DJ. ;llf4'1 011‘.) COLlLCA ‘-‘L\. \J [J\.' . E-‘f/lSAk“ CL 5. ' O KIAAU. ‘(x UKIQ... \‘.2 Kid T3140 C -' 1'; ‘3. TBS . -.. 2-.- . - -. --.. a 2. , .n. '1 . : .—., - 1"oa.*.CL2.LOfl ll’l‘.-'C2_~u__.-ff f1€£;\.l'.;_ Vu‘G 115152;.-- {£48m -.LJ....5 1.4-1211 . -‘ ‘ s - a n V w w R h. o ‘ v ‘3 ‘ q I A" ‘: " f‘. ' ’."-r ' r- .. . ' 3" "' 1‘ I 7’ "3 I 7 ‘ “V. F " ’ ‘r ". r ‘ I"? ‘ ‘ V ."l f7.”' "“33”“ a .714-f20c«.gi~.\,.'_ k2.-.;_k.-- -.~_Lu,‘ f1} u- O\.;._-O..l\. -. fl chl c.4.--:.g-'..-'.-.v nix/Ml...“ ..'.. o ‘ I ' ..-‘ 1 o ‘1 3 _‘ _1_ - '1’ "-<‘ -" ‘1“ " '\ “'2'“ ‘~ '. H “I‘ ’24‘ ‘ " *‘r‘ ‘ 2“" " 1 . f2 'H’Z‘ Ck. _ LIQ r£ _. .J_La.... L; T' _. (.3 1‘ _- J C --L: 1 Lv .41... L k. is.) Ut.e b/‘J OkkL/LC UU .U ' "‘ 1'} (r v ) - 1 77’3“}: . .- 2 ~ HI ‘ _.C \ ~ 3! «I, (J uh J l 2 :‘1 J- I t.“ ”7‘1... 7" - --—- \. m5... — d. \ L‘ 2" I Ow. 1_IL\/--. 3) , J91! l‘ \. / \C’IJ“ U. ‘/ rd"? * \nr"'": --‘-~ ‘ ~ ~“ 6 1 V2“ 7 ."-n. h d»: .eelwe 32L22222iv unrepOItea compouncs L;_Q prepgrcu "W n F?M“3'- .2» rf‘“ z" ' Min r ;- . . .4 ‘2 - . .. . 1 .Ll-JJ -L'J- XX‘LALJ._ \21. L‘ 4.1.2.1 : \‘ r" I :“‘ any-:1 IJ ‘ 7.1 N" I (‘1 ‘ J’I‘ ' ‘ ,~ ,‘~ L' ”K“ -’ .3. L-- 4‘2. -,,.\ .‘ x v 7:“ " -1;/.1-~-'.J.J A r1 '8 ? -1»)! "n... , ,. . V--bA‘ .1Ck.¢ , a fi r. 1 '3- 'f\¢ '¢‘-#.} .1 '." . T l ‘..".-k— Llfikm . .1. t .A—u‘. ,1 2‘” )0‘2-1? 4- » , LX116 12- u.— ..\l r“ ‘1" 'I’ \ ‘7' ‘ . 2...]; ‘LJ- ‘\_I-).‘J- rt.“ ,' " 3‘ r’\ ‘2‘ I‘- I \i 1. f ' F—i ‘ f 2 '. 3‘41. .. .L.‘ ..-L . .. I -1 I J T A ’ . 41-4 . -,.| _ .T. ,‘ | \_ \~‘ —_JKJ' L1 ,._ .;- ‘ 4. ' x A 5 C) « L.) "21‘ ‘ 1' fl . ‘ .L J -- , . . ‘ - 2- V—V ~r; . , c' ‘ I fia..ln---4 L ‘. v-o w R . ho ’ U ‘ ' 1 ' I ..;J A‘Dl .- \\‘ .Jx) \\,)_ u . r1‘ . ,_.‘ - _ - - fl ‘ " : 1 .+ - .I J - ~ " ' ,' , 2 ‘ ' ‘ , 22*."2 J‘. ."’ - .Lr.C LAQ\J.A(JF ’3‘, -A-\... u—u-¢-'\- \'O C‘&*/L ~‘\—' v-‘ - J.— \ x n a o ”\C‘.‘ ‘ r‘ “."‘ '-«‘~‘.r~. -r *n‘t- 1“ r‘ KIN; 2.20.. -~.\.) .1... '.l l.) . ‘.,/ \_'J 'A‘_- ‘2 .11 .2- V $3.1- k! w ‘ _ .1 ~ -‘ . 1 . ~ «54 1~ 0“”. w 1 - M53 f-'\*."~("r\‘ -- -\‘- 5- 1,7 m.‘ tint:- Og. ~J‘I-O J. K" \J ‘ A‘V IVU LL- k: .4 O .1. \JJ 4... L1 iUO-L A ’I ‘ o o ~n" ‘ ‘- A 3 4- ,‘-, C: u " " ‘ ' '~ ". 14-\ -~"“' \ - .s... \J.‘ Ul~-;_x_. A..\-..‘\-_\,-\/ J- _./ U o I g 1“ ‘7“ {ff -J l. -U ' 1 ""15 f‘";‘v *4! s‘ ‘Pi‘n A - --.. .- .J- 5 ca - 2—. ‘J (- «’1 \.‘. V 5’ ‘ . .‘ f‘ , g? ‘ A *tion A to -. r. J- 4‘ ~ ~- . x. - L) U ’3 Qt.) A INTRODUCTION . HISTORICAL . . DISCUSSION . . EXPERIHENTAL . SUhMARY . . . BIBLIOGRAPHY O O O O O O O O O O O O 0 0 0 'TABLE OF CONTENTS 29 77 79 INTRODUCTION . . HISTORICAL . . . DISCUSSION . . . EXPERIMENTAL . . .SUIIIANY . 7. . . BIBLIOGRAPHY O O O O O O O O O O 0 O O O O 0 'TABLE OF CONTENTS 29 77 79 LIST OF TABLES TABLE PAGE I 6)- (N , N-Dialkylamino ) alkyl-fi-napht hyl sulfide hydrochlorides .'. . . . . . . . . 24 I: 0- (N , N -Dialkylamino ) alkyl-OC-naphthyl sulfide hydrochlorides . . . . . . . . . . 25 \ iv LIST OF FIGURES FIGURE PAGE 1 Infrared Spectrum of benzofb3thi0phene . . 26 2 Infrared spectrum of thienof2,3-b]benzo [thhiOpheneoooooooooooocoo27 Infrared spectrum of thienof3,2-O]benzo ‘ [blthiOphene . . . . . . . . . . . . . . . 28 INTRODUCTION Benzofblthiophene has been known for somewhat over a half century, but aryl derivatives of it having a second thiophene ring fused to the molecule have had little reported on them in the chemical literature. The firs: part of this thesis deals with two attempts to prepare the thienobenzolbflthiOphene in fairly good yields. The remainder of the work herein reported deals with the preparation of tertiary.amine derivatives ofaL and a naphthalenethiols. Considerable work has been done on aryl or heterocyclic dialkylamino alkyl sulfides but none has been reported in which naphtl-lene is part of the molecule. A general investigation of such materials was started by Kim and Schuetz (I) when they observed that certain D-(N,N-disubstituted amino)-alkyl-—phenyl sulfides possessed local anesthetic properties. Epstein, and Meyer (d),and Luduena and HOppe (3) broadened this work to other types of compounds, all containing a tertiary amine group. Additional work has since been reported from these laboratories by Houff and Schuetz (A), Schuetz and Baldwin (5) and Heyd (6) on other possible anesthetic compounds of this general type. H STORICAL Lanfry (7) first claimed to have isolated a -thienobenso[b]thiophene isomer. In 1911, he reported the product obtained from the high temperature reaction of sulfur and naphthalene (iron tube) gave‘positive tests for a thiophene ring with isatin (indophenine test) and phenanthraquinone (Liebermann tert). The arterial melted at 118.50 and on oxidation yielded a sulfone, Clohéozsg (m.p. 130°) and a disulfone, 010560452 (m,p,125fi, It alt) formed a tetranitro derivative (m.p. BOOOd) and a tetrabr Hide (m.p. 247-2480). On theSe very lflnited data, he pGCosed two structures for this compound. ? @JJ or 5/” Hartough and Meisel (8) do not accept either structure. 5 since they claim that both of these compounds would require a drastic skeletal rearrangement of the naphthalene structure. They quote the work of Herzfelder (9) as contradictory evidence and propoSe a different structure. Herzfelder ;reated l-nitronaphthalene with sulfur under milder conditions to obtain a compound 010563 which 2 he assigned an endo formula. Hartough and Meisel propose that if this material is initially formed, a second sulfur may attack either the l-8a or the t-ha carbon bond to yield an intermediate which could react with an additional sulfur atom, witn skeletal rearrangement to yield, not thienof2,3-b]benzo[h: thiophene, but rather, its isomer, thieno[3,2-beenzofb1thiophene. 5\ \s Interesting as this may be, it appears from the journals that little was done on these isomeric compounds until about six years ago when Tilak and co-workers, in India, undertook a study of the carcinogenesis of thiophene isosters of polycyclic hydrocarbons. Most of this work has been published in the Indian journals and/ébgtraCt form in Chemical Abstracts. How- ever, Tilak has rublished a summary article of this work in English (10). Tilak and co-workers (ll, 12, 13) describe the preparation of both isomers. Thienof3,2-b]benzo[b]thiophene was obtained by the reaction of 3-mercaptothiophene with 2-bromocyclohexanone, cyclodehydration and sulfur dehydrogenation to the aronatic structure 0 H o $\\ \\ '~'- J *HMi’ {filer-‘3— 4 \S B, o s a \s a Thieno[2,3-b]benzo[b]thiophene was synthesized by the reaction of benzolblthiOphene with n-butyl lithium, addition of sulfur and hydrolysis to the mercaptan, followed by interaction of the latter with a haloacetaldehyde dialkylacetal and subsequent ring closure with phosphorus pentoxide. Y-CHg-CHMR)? / 5 SH NaOCzH5 *\~ 3 S-CHZ—CH(OR)2 X Cl, Br * ‘ . R CH3, CZHS . 4 I,’ - . P o , 853., H PC I 1 i Ogug solven A ‘\~ *' . 5/ s The work of Horton (It) on the mechanism of the reaction of sulfur With several hydrocarbons has led to the more recent work of Parham and Gadsby (15). They attempted to prepare thieno[2,3-b]benzo[b}thiophene by the interaction of sulfur and 3-vinylbenzofb1thiophene at moderately high temperatures. Distillation of the crude reaction mixture yielded a bright orange colored oil but chromatographic techniques gave only a series of oils. however, they were able to prepare two phenyl substituted r11 neir wo k may be summarized in the folloxln i der;vatives. equations} / ( + Céusromg , C] ) El ~.\-‘/\S Li , S or. 6115 1/2000 KIQ 'hhrs. 3~phenyl-thieno[3,2-b1benzolb1thiophene MgBr < i .9. €6HSCOCH3 H ,, /I y (“0 S .. 3-phenyl—thienof2,3-blbenzoiuithiophene 4—7” S These structures were confirmed by the unequivocable syntlesis of the two isomers. ,I’ i I SH + C6” COCHZBr _____._.,, \ s 5 ::L:6H5 ~ “(//’Eg;:Cl5 \, o PmiiT II The historical background of tertiary amine hydrochloride derivatives of aromatic sulfides has already been exhaustively reviewed by him (16), houff'(l7), Baldwin (18) and heyd (6) in their respective theses. The present author‘s work dealt with the preparation of tertiary amine hydrochloride derivatives of the naphthalene- thiol series, and was mainly concerned with/E-naphthalenethiol derivatives. however, a piperidino, morpholino and dialkyl amino derivativesoffld-naphthalenethiol were prepared in addition. Two cases of methoxy substituted naphthalene nuclei were also obtained with the aim of determining whether position substitution had an effect on the pharmacological activities of such materials. The tertiary amines used in this work included fi-piperidinoethyl, t-piperidino-n-propyl,,fl~morpholino- ethyl, f~morpholino-n—prcpyl, JLmethylza-dimethylamino- ethyl,43-dimethylamincethylrail,fi-diethylaninoethyl. C29 0f the purposes Of the Study described here was tr prepare the two isomers of t?ienobenzo[b]thioohene from the readily available bensofblthiophene. One of the first methods considered feasible to investigate was the cyclic dehydration of the arylthioglycolic acid with J) pho_phoru; pcntoxide to the correSponding cyclic alcohol. This could then be reduced to the unsubstituted compound, and is illustrated by the preparation'ol benzofblthiophenc. S\CH / O r/ SH 2 P205» '\\ I + Cl-CHZ-COQ}; NaOH ‘ £04330 This method would involve Lhe us» of readily avail- able materials and it was considered desirtyle to determine how easily, and under what conditions, the ring closure occurred. The investigation was initiated with thiophenol as it appeared reasonable that useful conclusions could be drawn from this series as to its applicability to the benzofb] thienylchiols synthesis. Thiophenol was easily converted to phenylthioglycolic 7 acid by reacting it with a molar excess of chloroacetic acid in aqueous sodium hydroxide. From that point on, however, results were n gative in the attempted ring closure. Severil different pro— cedures were employed; refluxing a benzene solution 01 the acid with an eight to ten molar excesseof phosphorus pentoxide yielded only a red colOred oil as the product. Johns Hanville Celite Analytical Filter Aid was added in an attempt to obtain a good suspension of the phOSphorus pentoxide but this again gave the same red colored oil instead of the expected solid compound. The ufie of a zer boiling solvent, chlorobenzene, o<:e again grve the sage oily material. In a final attempt, a benzene solution of the phenyl- thioglycolic acid was added slowly to a refluxing benzen , phosphorus pentoxide suspension but this too proved un- successful. It was impossiole toseparate any product by vacuum distillation indicating that none of the desired product . had been formed since the three hydroxy compound boils low enough (95-1000 at 1 mm.) to have been quite easily isolated. Attempted extraction with several different solvents failed to isolate any pure compound. This preliminary work indicated that another method would have to be meloTsd in the synthesis of the hie o- benzofblthiOphenes. . Tila: (ll, l2, l3) had pre iously prepared th: two isomers by a relatively simple procedure. his method employed the benzo{blthienylmercaptans as a starting material and since Heyd (6) had already studied the chemistry and preparation of these materials, it tie a siuple matter to obtain them. Feyd used 3—iodohenzo[b]thiophene which he converted to the corresponding C‘ignard, rtacted this with sulfur and hydrolyzed the product to the corresponding 3—bcnzo- [Efltkdenylmercaptan. This synthesis was employed on two occassions but was abandoned for the more easily prepared 3-bromobenzofb]thiophene which could be converted to a grignard reagent in almost as good yields as the iodo compound. The yield of 3-benzo[b]thienylmercaptan was improved considerable over those of heyd's by immediate distillation of the mercaptan following hydrolysis of the magnesium halide salt of the mercaptan. The halomagnesium salt was stored under nitrogen prior to hydrolysis to reduce to a minimum, oxidation of these salts to the corresponding 10 The pure mercaptun could be s1>red in the dark (00) for several hours with no apparent oxidation as indicated by its complete solubility in 15$ potassium hydroxice. Tilak reacted . 03- benzofo} thienylmercapten with bromoacetaldehyde dimet hy mial and obtained the expeCLe 2,2-dimethoxyethyl-2-benzo[b]thienyl salfide. Bruno- acetaldehyde diethylacetal was used, because of its avail- ability, in the first synthesis of the intermediate compound but ehloroacetaleehyde diethylacetal was used successfully thereafter. . Initially, crisiderable err): dental difficulty was encountered in attempting to purify the 2,2-diethoxyethyl- 2-benzoIthhienyl sulfide by distill cion, even at very. low pressures. Fortunately, it was found that the desired hetero- cyclic could be prepared by refluxing the undistilled com- pound in a benzene solution of phOSphorus pentoxide and 85% phOSphoric acid. The crude product could be cleaned up ea:ily by treating it with small quantities of norite while recrystallizing it from an isopropyl alcohol-water mixture. The purified compound had a melting point in agr;ement with that reported by Tilak for the same material. The isomeric t1-x1ienof3,3-b]benzo [b] thiophene was also prep: d u; ing f a procedure just des ribcd. The 2~benzo[b] A thicnylmercaptan was obtained as an unpleasant smelling solid by preparing 2-benzoCbZthienyl lithium fronl benzofblthiophene and fr.shly prepared n-butyl lithium, adding sulfur to the et‘eral solution of the 0“gano lithium compound and hy rolyz in3 the lithium mercapwide to Jbtain the free merca: an. It was not purified by rec sta alliz ation since heyd(6) reports that it is readily air oxidised to the disulfide durin3 recrys- tallization. It was recovered fn.m the hydrolysis solution by filtrgtion and dried in a CessicaLC' under a nitrogen a heap; re. It was always c} shed for contamination by disulfide by its melting point before use , (the nercaptan halos about 700 lower than the disulfide) and its sol- ubility in aqueous base. The mercaptan was converted to the acetal and cyclized to thieno[2,3-b]henzo[b]thiophene with phosphorus pent- oxide and 85% plespl oric acid in boiling benzene. This isomer was more difficult to nuriiv as only an oil was init'ally isolated on removal of the etner from the com- bined ether extracts. It could not be induced to crystallize nor could it be distilled (vacur). however, it was isolated by extraction of the oil with boiling methanol and treatment of the latter with small gurntities Banfield (19) reported some wc'” on the ring closures ‘l ‘I 1 of arylthioa cetalr'm onyde diet hyla cetzls. In his work, he cyclised naphthof2,3-b]thiophene in 92% yield from 2-naphthylthioacetaldehyde diethylacetal using anhydrous A .4 .j- - 'stannic chloriie as their FQRSUHUO rphis method, when applied to the benzofllthienyl- 1 I u A j ' W , 1 1 O 1". ". r] ‘ ‘ 'n“ Hrs _ -1_ o . nioacetalc.1yee diethylacetal sonels have thienof3,2—QJ benchb.th_ophene in a very pur state. however, the fi,3-b]isoner co; d not be isolated ur‘ng the same procedure. Campaizne (23,21) reported ;he preparation of "\ several condens d tiioy4enes by the rir; closure: 0; some‘fi-aryl-fl-nercaptoacrylic acids and their reiated \ disulfides. In this work tney condensed several arenatic aldehydes with rhodanine, hydrolyzfixfi the rhodanine deriv- atives with dilute base to their respective fl-aryl-.L- mercaptoacrylic acids and then oxidized ti? latter with iodine to a fused thiophene ring compound. H 0:0 CHE—C: / é» l I t‘ ‘COOH £73?th "‘39 ‘EOAc 13 The authors sugrcst tma following mechanism for this reaction. %\* _ ‘ . 4:6 - ' i ' ""“%’ " i J- }y* H Czc—COCI—I + / (329-com: l +-P1-—————e> SH -+ I QIZ \\\ 2 ,czc-co:a 2 SH 4' 2 I2r—év :12 ll}. ampaivne supported the disul ide intermed ace by ..) C) ring closure reactions of both the d-mercapto acids and some of their related dis lfides. Iodine, was in the used as the oxidizi.g agen ' for both the direc; mair, ring closure and conversion to tne disulfide. Solvents and reaction ccriii “nr '1ried greatly. Iodine in ethanol at room temperature (14 hrs.) oxidized 5-phenyl- 2—mercapto-2-h-pcntadienoic acid to 5-phenyl-2—thenoic acid. Naphtho[l,2-b1thiophene-2-carboxylic acid was isolated in 60? yield by treating46-2+naphthyla£Lner- cantoacrylic acid with odine in‘dioxane at 50° (24 hrs.). When the disulfide was used in the ring closure, the final product was isolated in 90% yield in a 50% longer reaction period. Rather rigorous conditions were used to synthesize benzo[u]thiophene-2-carboxylic acid. An.iodine-nitro- benzene solution was heated to just below its boiling point (210.;))n prior to adding the JEHDJCaotoc1*n"n c ‘ A; '9..- . A Very short reaction time (1 min.) was used to DJ obtain the product in 68% yield. Deca sexylation oi the acid with mercuric acetate in glaCial cetic acid gave a l6% yield of benzolblthiOphene. These procedures appeared to be applicable to the erzparation of thienobenzo[b]thiophenes startine with the appropriate aldehydes. The 2-benzoft]thienylaldehyde was canily ~repzreo by reacting 2—b0nIOEu1oul€1:lth3UH " I ‘fi TV ‘ _n} -0 .1. (u . ‘ f‘ 1 ’w ’ -W“,1 7h . '_~ - ,J 1.111.111 N- Jet Evilu 1aI1_:_J.l\lC. T111". calyx: enlO Raf-7 (.011th 1' you. :fiw- 4-1-, -. 1‘ --. ‘ . 3- -: ‘--I .‘ (1” {f easily to L a higi melting rnodanine te.ivacivc in om.hm 1 yielx. the r odcnine derivative was to démercappto-—L3n...o]‘1lacrylic aclu in 02.;3 ”ield. The acid was recrySLallized with difficulty only from chloroform and was obtained as a powdery yellow colored solid, which was analyzed as its 2—h-dinitro- phenyl derivative. Ca gaigne reported similar difficulties “1 the recrystallization of t1 e d}.1w to carbonylic acids. Hartough (8) states that resonance cansiderations of the benzo[b3,hiophenes mrst em predicts that electro- philic substitution should occur preferentially in the 3 position. (III) (II) Formation of III requires a resonance in eraction between the benzene and the heterocyclic ring which is not necessary for the formation of II, resulting in two ionic forms with a negative charge in the 3 position, l6 while the 2 anion can have only a single form. :fl“ - ~h ~-r. ' ‘ U. ‘ . ' lNC\0 scenance cols1dr"itio”fi sungesred that ., perhaps the thienef3,2- it) JMJE “onioelcne-Z-carboxylic acid could be closed under much milcer conditions than the benzofb]thiOLQene-2-cerboxylic acid. Consequently, the first attempted ring closure reactions were done in absolute ethanol at room temperature using iodine as the oxidizing agent.‘ This procedure, however, resulted in only base insoluble material being isolated. ' \ Nex , iodine was LSGd in hot dioxan- (steam bath) as the ring closure media, but again only base insoluble material WTS i elated. The hign i-nnerature (ZCQO) use 01 nitzabenzene and iodine again yielded no cyclis tion product. Since Campaigns had shown that the mechanism in- volved a disulfide internediate, it was considered best to attempt to prepare the disulfide of the benzolb] thiophene unsaturated acid first and then to proceed with the ring closure. Treatment of the nercanto acid with iodine in absolute ethanol at temperatures between -lS to 00 failed to yield any disulfide. Following these failures, an attempt was made to find a more efficient oxidizing agent which would selectively convert the free mercaptan to it: di ulfide without oxidatively attaclin; the siL chain. It res anticipated that bromine night accomplish this task well but it wouid be best to first compare it with Campaigne's work with iodine and benzeTthhiOphene- 2-carboxylic acid. ' L Ld-xerccptoclLiaiic acid was prepared by hydrolyz ing the coniensation product of benzaldehyde and rhodanine. its iodine oxidation proceeded s: loothly to the dis ulfioe as reLm ed by Campaigns. When bromine was used, the \ diFalfide was formed in’9ffi yield. A nizture melting D point of the two disul fides obtazned hy the iodine and bromine o: chL'o”" was' identic.l. This initial success led to an atseupt to prepare the oen~o[n]tiioonene 2- ca rboxylic acid dir ctly from the substituted cinnanic acid using bro in" in place of the iodine, conducting the cycli at ion reaction in nitrolenzene. uCCb difficulty was encountered filth bromine in reachin g the higher te - e1ature and severe spattering of the bromine-nitrobenz ne mixture forced the addition . . .. o r ,.J_. of the «EmercaptOCinnamic aCid at 165 . Phe nel ting point and unsaturation tests on material obtained in this r action ihiic ted that although some desired F-) r p product had been formed, it did not compare favorably with that obtained by iodine oxidative cyclization. Since the bromine oxidation of chercantocinnanic acid to the fiisulfide had proceeded smoothly and in high yield, it was sea in absolute ethanol to attempt to oxidize dymercapto-fiLZ-bensoftflthienylacrylic acid to its disuliide, but without success. At this juncture the investigation to develop new synthetic prOCidures to obtain thienobenzofblthiophenes was discontinued. ' Th(re are two methods for preparing UL(N,N di- substituted amino) aryl sulfides. Kim (1) used a method which can be summarized as follows. , g ' /,/ -‘ 50012 . i kn ?\ This method suffered from several disadvantages. Ehe akhydroxy compounds were easily prepared from the cor- ;eSponding chlarohydrins but conversion of these to their chhloro compounds always had to be carried out under . carefully controlled temperatures or considerable tarry material was formed. Reaction of the omega chloroalkyl phenyl sulfide with secondary amines usually resulted in low yields and it was often necessary to carry these reactions out in sealed tubes at elevated temperatures. Despite the general procedures shortcomings, a few bkhydroxyalkyl naphthyl sulfides were prepared to ascer- tain whe*‘er the yields obtainable would compare favorably 20 with those rapt“ ed for the lower molecular weight aromatIc s. Further, a literature search revealed that fltfl'thionaehthoxy) 1 thyl alcohol was the only compound of this 1.e ‘ ologous {‘1' series that héd been reported. he n~prolyl and iso- propyl alcohols 1.ere prenzred and charasserized in the present scudV. 1 An attempt to convert,3-r1n1t*"‘-5-nv xy propyl sulfid- to its corresponding chloride with thionyl chloride evealed clearly the difficultits reported in such preparations and urged inmediate'abandonment of this \ general approach since it depended on the intermediate chlorides. Fart her, previous work in these laboratories had Jade ava ile ble a good nux1ber of LL(-.€,N dialaylamino) 315711161115105 for a2 alternate procedure. The second method for the synthesis of disubstituted amino alkyl napht1*.yl sulfides involves the interaction of a w—chloro tert; ary anline hydrochloride with the sodivnn r'alt of the thiol compound. ‘Sr—l ?)n0120U szh‘+ Cl(CH2)nCh20H __ >.REN(C R2E=I(C}2)nCIZIZOI___;Q1£3£/_:_L,2.> RZT-Icz—IZMCHZCJ. 'hCl c) O :C A) A C) n: 1v 5 2'). R A) a? PL2N(CH2)IIC H2Cl‘hCl > //’ ./ K/ W 1\) 3...: This latter general nethod was she one employed in the nresent study to 0011in H e L%(N,N disubstituted amino) . 1 1 . ' cw: 3 a 1‘y1 nfi.l)£.t m fl S'L -—.L O S O I‘""1‘l ‘1'“ ' '9 q ." -,1/~~ '. o ‘ 1 r. 1“.“ . "‘.'+' J ' 5"“ 38-u1.13 thale tthl LuS r1tpnred QJCubchulVGiy by 1_ '1 the redwc‘ on of,J-nanht;: lencstl onvl cnlor 'ule, and some of it was rurchased from commercial sources. Table I summarizes the sev1 al tertiary a nines , suostituted for the hydrogen of the swlfhyc1ryl group. 1-» ‘1. 1.3 (D anir1o sulfides were isolated a (1’) theil hydrochloride _ - - I and were all recrystallized from drv is0propyl alcohol with U \ the exception of the ninerioinoethyl comnound which was rec rys allized :rom.easolute ethanol. 7he structure of the o‘cithylarino-1sopronyl naph- thyls le ce was n0“ definitely established. Ea ldwin(l%} has reviewed the possibility of an intramolecular dis- pl? ce1~nc reaction or ioniza ion resulting from neighboring group pa ticipation of the itrog en to form a cyclic onium salt in nucleophilic substitution involving3fi-di- alhylauinofifi-alkylethyl halides. Such an intermediate on a bimolecular attack by naphthyl sulfide ions would probably give a rearranged product, while if the initial 30 (x) step in nrcduct formation nas'the ionization of the cyclic 4 1 'tnylene imonium ion, tre m t tinimooynamically ataole L .‘ K _ ~—. a. ; -¢ Y ~. r-, J'- r- T1. — h ' 'r\ n -- \ - 4— - q luh. .? —. - D‘OCW CL! T'OUld ”It”: Gluillcgwib‘. l..'O CLASUS Ol 1:110 3-1-1L1L,1'LCUJ_CJH >f. n ‘ _'--. »-.Ifl. I‘ fi‘ "I" “r"vv ‘1 1 o.-.. [ca-I721)?” ”1131101141101 a.up- i we? val .qj-1do-fi~11.~ei_.i1,.l o1 {13.2. chloride grve ore DTOdUC, wiich recrystallized very eesilv, 1 1 -= ~ melted snarpiy and analvze: C01 rect ly indrcating a single 1 isomer 7 d resulted. .1 ine n emanation of the¢g— “3&01 ‘8 enethiol plwe cnted ~ 11.; 1 .’ ‘ 1.“ methods more at me1;‘ :ed out CO 0 3 C) F F:; 1—“ 0 $1 F: P' C.) o (D <: L .3 ' J G) F! all were abandoned in favor of the procedure involving the reaction 0: sulfur with an {Vnenhthalene(}rignard lation and O :5 c f U F4) 0 F" F J Q 2; (I) c); C“ ‘A ‘1 f7 ' i C 4 J O }__1 Q A N U) '_1 U) C rt 0 Q L , ) Q }_J 3-: U purification of the erylthiol bv distillation in vacuo. Even this procedire resulted in low yields of the thiol with an extremely unpleasant smelling residue remaining after the disti lation when steam distillation was not Th”ee amino suL ides were prepared from «Enaphthalene— thiol and are summarized in Table II. ’ pron a synthetic noint, perhaps the most interesting compound prenarea was ’Lmercaptoqe—met hoxvzaphtr alene, since it involved the preparation of déthiocyano13-methoxy- naohthalene as an intermediate. Kaufmann (22) prepared this latter material from .6-methoxynaiphthalene (nd a SOl‘ZtiO‘fl I 1-) 4' -'~ F' ~r H r‘ v- .3- of the free iocvan gen. A iev Jeags later, he resorted that several tnioejanete connouan could oe synthes'zed 0* 1: 1 Y'I'j 4“, O 4-“ 1' \\ '1'.“ ’3' hr" 1‘ 1‘ ’1 b ‘ V" 7 0V QCl (AT/13f: L“... IJlliOCfc.i10gt,ll "loll blu Lil C iroul CR8 SOdlUL salt d rectlv in tne reaczi n mixture. He had _- -“0 . h‘ r . “‘~"q‘. 1 4.1‘r“ .VAI ' ,a _ I _ ‘ ‘-‘+” ole/lously es tviished t.ac tnioevano,+ UIlLCL his l L saturat,d compounds -JJ“.EH1€;CLlVlLy oetw ' r1lw'n and iodine. He exclained the brcmine liberated tniocvano gen . ‘ ' -: V. .. .v A ° .-1 ’- 1 . -. .,,_ sucstituthA leic on in one i .1...-1.O‘.‘!l..l\D manner (23). lf aniline, :or exannle, in a str Qv ac‘1ic sol ition -~ -h.--‘-.3 . .. f‘ vwf‘ rd- ' q~r4- ‘ -:- -‘».I 1 . 1 COHLuleflg sodiura tM )CVuLuuC, is tie-ted in t:e cold Wltn V ‘ f“\ r‘ T ‘ .7 “es-5" ~ ’Tv-Wf‘“ qD . .1 * cronine, the reaction Zhuuuh +'Br2.___, 4M air ? (oCm)2, bein e ionic, proceeds so rapidlv that the reaction C.) "I .A * 72. o... 1?..‘1 .0. ' ' -'. a. CéHSHHg f s-2._~m, bi06LhJTM2 Br is newligible ii an excess of sodi um thi ocvan ate is used. The hydrolysis ‘ . \ . . . . reaction, 3(% w;2-+ LEQO ___> 5““,N +hZSOLP i-hCN lS greatly retartk Jd in the presence of the acid and the zinc is true of the polymerization so tha‘ unc r those erred by forming thiocyanojen in a glacial acetic acid sol. ion 0 /"m.tcnoxvn” mi thalene. The product was recovered by filtration and after drying its melting point was 300 lower the n reported in the literature (22, 24). An infra- red snectrum of this material ind icated both an J;fi3 I substituted naphthalene structure and a free sulfl ydryl w - -0 u Wr . «13-? a u , ~ m V group. unalySis Ol tn mateiial eased on a mereapto— methoxynaphthalene structure,for carbon, hydrogen and —p<\ fl " . 7. A " “ ‘ ". 1‘ h” '-‘.4 "\ 13-. r- - suliul ShOUeQ asreement within O.mfl. 1-0m this ‘apz V _' ,\ A "‘ ‘ ‘I 1_ r~ _ , p ‘ ‘rtv- _ ‘r‘ ‘ a _ 1“: ‘ _ n we a _ it WgS CaniuaOQ that ruhimaflu's TC'JTLCC Acltlnb pOlHL of 980 is incorrect are that the true melting roint of . ‘ 1 § 1 I o / 3 démercanto7fl-methoxynapnthalene 18 080. = 24 S .2 ea .2 2. 9 om e. we 2% mo .E mzaosmso :2 Amvaztmukmo- 8.2 3.: 3.0 is 3.3 3.8 mzaosmzo 22 AmmoVkaokmo- nmu mm .2 mm .2 2 .e 2 .5 mo 43 Na .8 mzfi ammo 2; Nanmovziokmo- 3.0 2; was 36 N23 3.8 mozaosmso 02-m.a2©-~mo-~mu-~mo- 3.2 3.2 310 2.5 923 3.3 mOZGNmso $2-22 o. Kareem? 2:. 2; Se 34. 2.3 2.3 mzaosmso m2 Oakmokmokmo- $2 212 8.» owe $13 ~23 mzfiosmzo mow A thutmo- canon .330 38m 628 cases 628 m» udmfism as Gowouetam . 05 ~83an mfisgnoh 0 .nm .2 m 0 $282833 22:3 SeamusAffliofififlsfifin-z .23-; 233. Gm .m-m 25 $5 36 Se 3;. 3.3 3.3828516 32 £00- 1m~0vz-~m0-~m0- 3.2 3.2 omé 3g 3.3 3.3 mzaosmsd 323.2; m Anmnuvokmotmo- 35 35 Se 2;. 8.3 3.3 82203220 332 £00- .-~m0-~m0- is 22. 3.3 3.3 8.3 3.3 mostmzu 3.32-32 m A Z-~m0-~m0-~m0- 2.2 3.2 3;. 3;. 3.3 3.3 920.3320 932 m A z” -Nm0-~m0- .358 .330 venom .330 38m .330 . 05 udfidm as Gmmonwhm ca GOQHMU mfidguorm .Oo.nm.2 am in $283833 0228 HERE-..43220282335-z .5312 23.3. N m Gram- 26 Amnon 0383 gumnoamkfim? : 3 o w . p - - - 3 4N4 «PM _ d d a > C J. om o¢ low Q .AGOEBOm JUUV econmoflfimfloucmn. me 8550QO 00.535 .H mndmfim -J OOH uoys sgmsuexl mag 19d 4] Amcon 015 £umcmfio>m3 S 2 S C 3 v m i p e m w m q 4 4. . J + J 1 d . q 1 fl 4: .AGOSSHOm JDUV mcmfimowfimfloucmflnum .2953» m0 guuummm wondumcm .N ”:de om ow co cm on: uoyssywsu'exl mag Jed Amconoflhv nuwcmfimzwg w; mH mm 1 oar o w h o m w m J. m a 4 . m _. _ T m A. Low loo . cm on: .AGOESHQm. JUUV ocmgmodfimflouamnmflnm .mwocofifi mo 8.9.30on UOHMHHGH .m wudwfim uoys symsuell zueg Jed ‘v— - 1$.'Lll-fi. .lfl-LL‘N -g': .L. :n~”"ioc;t:ao:qmg:etix: acixl A "fi \1 / EF-x -C/1-Q-COOH i ' " \, l , \__ 71" via ./ I: a « ° -,, 1, ... 7... ,l .i; a; ' ‘v - a s,ir e , hull Sulho Oh co. aiming lt é. fl r'_v w _- v! J_ .24 A a “ :_- _ -. . ‘ Ir‘ ‘\ (u.Cs .ole) Cl m-oLlOvleuOl cissclveo in 5d ml. oi 'W' . - . T.‘ A" ‘u : _... :‘ -. )q acueOJs Lawn SOldtnon, has a3 Ga 3 . —. -. . ..‘ (O.i¢ iole) Ol chloroacetic aCia. fl '- “2 a ‘, ‘ ‘ ("‘1 ‘_ f‘ -_1 -fl w s WulmCQ on tnc steam batn i I.(.A 7 . . r (1‘ q “—3!" 4‘ . ‘* Y H. ‘1'":— ~nti l LC~C U104 1A 44-Uure or an hour, ccolec, strongly acidified with e h LzSCL and JILracted twice wits ether. TKe combined etheral CXEFCCLS were in ttcn extracted hit? two DO‘ ions of 5 % aqueous NGLJO) so utiin. Tie ‘asic solution was acidified with 6 N H280, ind cooiec (ice bf h) to precipitate the product. Recrysta‘lin"ti0n from (30 - 3”) gave 11.7 g. (0.057 L018, ‘1 A ’ /‘,O .4_ _fi_‘_ mElblhn at oo-oc . Literature value, \ | netrolc 11:. ether 713) o . 67.5-bo0 (25). f the Droduct I1 .73 A I ‘ J ) \. fol \a :1 --.‘ “. ' “‘ ~ . 7-. 7" . . —,—'~»\~ , -‘ i lic. r* en” oven on i; .,ECQ*LPd 33ccc Q ~, il g. \,) 1‘. ‘ ~: m -\ V.'r( r ‘1 z" 1 -: a -: a ‘ F 1 1|" . -) Ol thiopn,nol has tiseoiVed in oiit e cl all C) O F! b 7..) O "a a -4 ' I n 0 o < ‘ a - .- . .- v. «'1 . - -. . 2 '2 . arm is. g. t3.2 Hole) oi onioroacetie ec1c rag acce . 1 V - ‘- v? - +P' ‘- ‘- — ,. J‘ - r -, ,~ A. ‘ -. 5' 1" I~ .- I‘ - Isolation oi c2e orouuct yitig.a i, 2 U. (u.u;; moie, 9/, 1 —- '- ‘,. t' nr-I - -. r xv- I ‘ . ~—. 1 J- .: - -I' - - ‘-\ vr - '5 2 1- Wm. Q1; ct; '7‘ f' l‘k' CI‘I'L' «1.11.3-1- “k ciOfl iI‘OJ. 1.0L Thai JCT . NHLLKJ‘u at ' . O T - ‘- O v ’ ‘ “ .-' , 33,- - ‘2 5 ,. _ "1 ' f‘ 1" J) o in). dWE). ':~ “Lire ‘fCAJ: .- \ 1 ~»-- ‘« - -‘-'-(v - . r‘ R. - ‘74“ ‘- ‘ wiicn coal“ Lie se Cr:om,.li120', inul i c, nor encracced - , 1 ‘- '_ _ ‘1 - I’ J- ,- . witn ,unuane or not Mapcf. ’W n . - l .1 ~- ‘ J— v — - - - N A '— L/ Q I“. :6an..- CLtt/etlo'u 1 (.15 1.180;; to r- t; ’)k “(3 w.-': ‘11:;‘(1 .L():\‘,f- W 1, n‘”‘l""\ ~_¢‘ L1" _- 1‘ .1 ‘. 1' 4-. ;i,“; _ N "'(‘3 1 «\r'] ‘1‘- [“1 r 7 : q . -. k);-1A-'_J'\/ L1,; Li‘5—LODLAGLLQ DJV" “CLKLAr-la’) tA'L\l DtlelLJ *LlllOCJ—L} CO.‘—-LC (afield . ‘ . P P ---. car. ~— '- — r. /\ 'h-I . fir-t ‘. -v' ,» n. D QlSSClV;C in /p .1. o. be.=ezc to a r i inin; solution ii . '* ' ~ A. rm .: - 2, n A . . - ,. - consene-ceiite-P2u5. inis pro eture le.d to results V91V d simil r to th s; just described. :7 -: A..t_\ 1C .15". e (‘ k ‘ I A. A. J- f u 1 70 d c r‘ L.) b (1 W :1. 4|- U , z u . .s O L "a a p“ ;_ d . a; 1. . O ..-_ u o .1 n U 1n 8 C C .M u 5 ‘ k . . u .l n +b r .i .. m . 4 V r f r a 3 O l S a: * 14 CO 0 “U m... «i .l a a H , ‘ . d T u 0 f w. r o \l/ O n .1 C P! \U 0 fix 10 r » cl .,.7 r10 . u ) n .0 0 Z A n l S O .1 n m 6. . ..i_ .3 a O E .Q ,. S e 2 U. i O 2 m D C O r X l , .m. ‘ .xL \I/ .1 w . x. u in... 9. O . C C H u .8 t r l e O . .2 C 3 a C ml [C u . 3 r .l .1 L a“ f\ n ,( O ,- . 0 rs n¢ a m; e e . . i- . n“; .3 «U .U S r n an.” k.“ L. r). \J O /\ u M mi , T 8 € l C S t . u ; a ) wi . s S e O 0 up w. , . m (x n C n C x) s, .; FD vs Au a ps .1 e 1 \J ) ,l I '8 ‘II C x ; fl LL C ,1) rt 10 “HI-IL .I w | pt /:! J. “a 01 7 -¥-. 0]. f‘ i" {4.13 U? Izrc, fl LO 0 /\ FN 11%;“ Hi“? I ‘\ .' x‘ a 5.1. ’ ”9...: ,- ‘ 1 x_gL\L p-14. c‘_..u “TEN. 0.53363 0218 . . ‘ CL 10( Q,r“‘; ukfl ‘ “as (7 I- u r I“ .Ili.’ .9... in". 1" -‘1 VIC; I ~1- ‘ 7-- l 4- ~ . L1 ’ . 7 * CLO i ’d “\ \l 1 “'\ 11.1 C0. r-a I £17 .A— J to v4, ‘ 45-1. y: 10.; 0011 Y'Ort rug} 'H ,3_1 L2 6 ,(\ n n n“. "H. Vb. . 1.x. «J. l S .. / .mk C .l a C r1. 0 u C. r 4 — . n . .1 744 m. a,“ .1! 1 r“ 0 e TV! Iv h (:1 h 04; "’\ J.‘ 2 \g (3 v f \ 0 r3 , Q C . L. ._ w T .f an 3 TL III! . . .(K C L C o n 3 H . o u . (U Lu .« u C a n. O l u T ._ L 3) 7. 7... f. a .. . u C t M u m .. f p ,h n C r P .41 . e O “A e a .s .. U u :4 U h.“ C 1 \v r e C “A. e - .u .Tu & V C r C A ' I V R » 9. ,‘ "x V O 3"! w L d _a O O '- , f \l K‘ 1 11 r”- k‘ \I I1 A I 5 L; \ I 1 C‘ :1. t ‘ i t d- ‘ CL I r0 0 sSClV i (r '3 0., t C . \l A -n \I i 3 A "5 Cr. .1; l“! O a O F? .l .1 \to solirti .. .4- J r? LA. 3 O. S Ynf 1.7 V‘ ‘ - l . W I 11 ion, a]. 'N ‘ Ct 4.549 o-‘U 1-1000- st to obt r~ O ‘ - .I, F‘ s, .1 tne Color H 01 pg 0+" 0 I V‘ x | £ J. u- 40w i0: — — ECO =1 1* ut 1.6 I - .1 H. .I -v OD ., alel ., :3 1 '1 n J.» A- (1 P) l 070d 1n .0 ZS I A l wh A .~ 08; 0-: ~ / 4’, ails . OTOQ lfi" '\ ; z - e 173; S l”. rre col 1... 1re value, (zen oran "H ~. .K.'-, . . "I go“ 8. a--. _. rA'. In a t;o 1' C? I “69 “Cs?“ flaiV c; infea Vith no 1(nical st“rcr, d PUTifi" i;nnol, rcflui connonscr (with ?”infi tycc) an- :hcr: : no; 59 ilac<‘ soc L1. or rrv g ioroform containing 71.9 g. (3.576 701") a? 1N'77gibgaflfii‘3hefi? (my? 7Q.C>;j. (0.8513;u iC) oi‘ér”Tydrous sociwi 3thafiC. axon no, 67.3 g. ($.5L6 moi ) dissolved in 70 31. 01 chlocofort was a; 0d dLrin: 53 mina*os, knowing the reaction tcxoorcture bouncer 23—250 bv ex erna cooiinfl. 'During the max: h tr, the St'rrcc reaction mixtwrc fioo? n a croan colowction an heceuo quite thick, nocossitatin Lhc €d(ition 01 103 ml. of distilled water co dissolvc inoc3cnic cc ts. The mixtu e vas trans- fc“”ed go a sooarat'rfi~funucl and extrcitcd With chloroform. T‘s cxivro'orm i yer h ; Eava'atec, washad with 200 ml. ‘ oi‘xiufpzr, \LIIT 3 fit” if“ ~11. or“3ic;:s CL? 5i§ acploOLus H? 3H, again vizh 2?0 mi. c3 YTC‘T aui Jinailv with ZJO mi. 0; satura.c4 cocium chloride afuc“ which it was 5‘ ter through anhfdrous sci um suchtc. The solvent was removed in a 110 H . DJ sioue was U “ ’1 1'01". 1“, \‘5 _ A. V J. 5 I 11"] j. t :1 I' '94‘ (Cs; {I er. 3 mo‘ .L w- ._ .' ., _._j . “A ,1 _- ~ _ .- ~ g ,, ‘_ ,- ’."‘O ‘ .. .- to o Vain tir 5souuv.‘ 134 //\\ um“ I.. t ! I! i , . : ; i I SH (1 o . ’7 . . .’ “ . . . . .1 . 1 . .- .1- 1- ... ' .. in a Jud l. .-QsL cqniohco wit“ mochanical St- 5-. .4. .' " I. ‘ “ 4.. .-, v. , 4": .1. J- _‘ .2 - ... ‘ ..'_ .. a. .1N) d .m-chtx: aoswoto-:3 (0-“? ,JJILCgLYTitjq a ;-tro(u3n I 0 " . 1 _ .~ V ,. u -- gj' S : "1-;1: Ll-\1 Jug}! Tastgtwiziitzla‘e 'ti:@:?ixixnzt;§1“; 'tzle Cfti e}? "7 ._ , . . V A. ’ ‘n q ,- ,A -... fi .., - I ~ A ~ _V Q h ‘ a snowrin: Junie; aHL t-ia coaccnser), was oiiced ' ' . v. rd 0‘- ‘r - ~ - ~’-~ .'-? J‘ ‘ "‘ ': 4' I ~'. 0~ ’- 'h 'r‘ , n SiH’nggjlr .1 bile £19770 «p-13 1., L, '. 11.1. Lil‘OKOJ. ,‘F .3) luk.’ 3:11.. 01 c '**~w :42 ,2 vavn Q.,; 1 z r. (u ”: r4 i ) -c 1:-1A4-n LDOVVJ. 4.4;- CL... .LOK; GOLJJJ. {-4 ‘L If. (I é? . .. .‘D/ 4 .040 4 O-.. 4--~LJAL.L.L1XI’1 notal. {‘1‘ r —. I ._,.‘ ’fu- _ - “ ‘ 1 A. r“ ‘ .‘ 4‘: l H . x in» crontiifi isnncl has A-.Heo Vita 41.i 5. (U. n “A ‘ -: ‘1 1 4‘ —W X - r-, "I. - _ ‘" ili c u-outxi bro ide oiSSOivcd EU .1. f‘. I.) T081013 101/1 'L'J'CC‘LS 4- '- 4—7.. A v\ ~ J . ---, bhe et:crql n-“ tyl o- a. - -J ‘34—..- 4.3-, ~,r\v\ ,J--T u:lf'b.i.C..L by , b5;€ L‘\:CLC.' L. 4.0 not-1 isonronyl alcohol vr . .1 ’ . " .1 . was continues at Q rat '\ f O _. ._. A. , 4.. - . 1&‘64; .5 j—L'C‘ U'L:_ ‘6 O..- -_L.\' . (:- L" l L . initiated by accing n~~.r‘ --‘-. ‘ 7 u ide solition ano a n immersed .1 . A ,3 z -. ‘u.( as. a 11W ml * the fir in a dry tion of the n-butyl brom p.72: .3. 4- J. , , c suiiicicnt co Jaintain a re “11‘ - ' ‘ rs W. ‘ -Lc reaction has comfilet U OY in 60 ice- i 0.9 action r .4"-L. 1. 1.. .' . . 11 V 1.0.1 -. ‘ .~ 1 .I. (. i-L) L Y .I. :C‘ I. \ao. "' ‘5’ Yu" (.-. . L.‘ 7 I”) .'l_v‘iu ,r\.", U . A /v r‘ C.‘ into i a C. U L. Vt" 4“ I‘- J. Fl .LvO I“ C». 80 3073",; 1. ~-t 10 COT.) r-.. C :4 . h VC C1 “ ..E r‘ -T_ - 1... L-ALU \)U... C r~ J. 7... t .- , . o a; to o “O \ '1 Al.“ 1 \ln. 4-. on my toil 1 V tom ILC ‘ ! C071 —. . ’1 x. ot COL| |‘/ L.\/ .-O 3 -,- 4.63 .01 f ‘1‘. CU. J. O (~1- — }fl\'\ u v‘...'-¢. .L J -1 . ‘.'"‘T‘~ 13.," A..-,-.kln'_ - fi‘fl'j ' ‘,') .3. ;C ‘ 10;. .'—A 7 ‘.’V CL‘1(. . Thu mi. T053011 J. . .LLJ. U 4.1. n... v1. 13!”: “.1- \ 7-) kl ’ .J ')0 (~ .1— ...A - A A (- . Ls 'x/Ol.‘;v (: 0.2]. ( C“ (‘5) ’ e Don-Io Yb *0 ti uro to occ‘ ... .: .,.4. 1 ~ J.A-L4‘. '-l >ction a U. ._.u A l A I 311211 C00“ 8 qr J». J—U 4.), e p‘ .- ..-L--'_ uuiOI 10?“ "\ aturc '5 7n \nJ '* fi - 0 "pg n f‘ 7v ‘f‘- u\ r‘ f] ‘\ ‘n‘ ~v I '1 - —- 1 f '1 \ - . r. -. " 4 \ I out. no. t. ..L-‘ In _‘.J.-L.\..U. k 01 ) L on 3 , 1" .-, ;- /. A Io... .‘ \ ‘ ‘ — A a . .5 , . « p - 4 I u . r ~', f "'_ a ' f ,, r. - (w "".Y\’ ,1“ - r\/- '1‘»"." u‘ ~~l ‘ ~‘, A 3 "".'-‘. r r‘ - -_q-.'-.l - A1 -\/\--L C.._)_'-)l \Jkt ()Jci L) .4 '~-. \.\.J'- (--J-\L, KL '(Jui ‘x’J.LIj_.'.-l'."2(\.L S‘qj-. L..-I-d'1,(j: - ~ 0 '30 . - 5 “ O . N 3" " A -\ - 3“ “ ('- r. .1 ,' - H (a. -- .’\ (K - .7 1 '. -'— I -5 r: (‘ 42 '-\ J- 4" ; j -. ,~ -q (fl ‘ ~ ~- ; \v\“ \IKJ -——-_-L -‘ , ¥ U—L—~\t]_.& J—‘J . '«U {—1.1 ‘.~--3)J C‘ \./L-'A'-L' I./- 31....-L4‘. ) L;"\/~-._.-CL. ’7‘”) 7’: "‘ 3'.“ 17'" 0 than )Yrfi‘rinrj- ""f "-7 '7 +10" - xv» 5.. d- 4 4/- ~. ' A‘- ‘v -L. Ll VA U My .A. \JK’ V k4‘A- Vk'. U v‘ J__._.--U_ (A Ui01; L.“‘-_‘ f.‘.'.:‘... I 1.x(el’. 0 ‘4: 4- 13h . ‘fi‘ (3 -‘ y.-. r. \1‘ff - .l‘; r.“‘ - -\-¢. 1‘ ‘4- 7": ‘--‘A \g“ D 1 .0. ‘fifi 1 v. -L-.L'.‘.\J ”A1 (4-.J.Ou um). o ;.l‘.3 9--OCL'J.C,\J, v.1.uL.OcLLJ 4.1;]: !.K.... I .~ 0 , n - . ,1 A0 . 1 v.- -,‘- - n '\ ‘f - , 1‘ \ -—‘ 1 4‘" {3 r. - l " l‘ ‘, ’0... J....ch.1u.LO “win”... no And-.3”: ciflv. ‘4 p -. , .- " _ _ H nas counicco-¢ sciubic 4. ‘ - .. 1 :4--. - 4. - -,. . - 7 P‘ "j .Ln 1.,» 1.0.. 1,_Lo.:i'aou:c value, 111.77. ..,_—-.‘,3 (4‘1": L“) .’-r\I‘I-‘- Ca ':'\J--C\§ i... :3 h ) r) L) (D ’-- ' r h (x *‘J H 1..) (J C') ’- 7 (J n H J ‘ J O [—1 i ,4 p) "( , ' 4.. - .A . - A ' '.‘ "7 .. 1 an: L1,r0fien {is -uict. urn alactd y./ g. (0.4 go c) o- 1"".r ‘ \ H ‘3‘. " ‘3’ pm Yc’i ' ‘ "7“." J'}r'\"' '1 “1"" 4" n C ’. .16. _._.]L n V...L \) \ Lxl DU 11.4.. 0.... k’f'd; CUJLV . LO L’A‘..LJ ¥I(’Q ‘ r‘ j Z ‘ - -" 'n '. ' f‘ ' t‘. .. f" ‘ ‘ -- ‘ ‘ C" ‘l ‘ ' \- a I ‘I ,- .1 .f.‘ at.-o c: ”rise, Ofcr l.) 1rs., 9o.€ g. (0.;o Loio) oi ( ‘\ 3 P ‘ J“ ‘r “1 -. ‘ ~' r : . ‘ ’V‘ [7 av - '3' 1 J -;o oven: ...- ionic c- so-Vco in /, ml. 0. c “or. 3“ C-«w;_r:-‘-'.:-i 0"" iod‘vwrf: I-V'ZC‘ 'tr’rqrzd +0 4V1~°t~°"tq 4-7'-‘.:) mac c. on .L .. J tbCl... .1. _'-1L\.o MIR-..) C!\,x\:.~_/ U .L. _L ”.0. L LI.-V .. \JC. 4-]. 0 ll '8. h 1 0 --\ M. ‘.- f 1' A _fl f‘ - - .0 .0 l -o 1 a. q r‘ _- -, ”_ _: ‘- ‘1 1 ”£383 ddclng t > lcto 0c.clic iocioe, tic lodction miALdle ‘L —1 "\ In - 1 h > 7 1 -. 7 . v. \N J- N . . ". I h has re; llxecx i0. 2 nrs. .t WhiCR DOLAU a CoRSiccrcoie 37 rm. .1 n 7‘ ‘ _ . + .::‘ J ,3 , . ,‘ - \F a .. -- - ~ I . , " ‘ -: - , n - w ‘ 0‘ «flu 0* ho¢EUE¢uA -D¢Li fulfilnud. n;u3“ cool¢u_ who . “'1‘ "\ ‘ ‘ fi ' V‘ 4 “ ‘— '- r. ~ . x -. r «A - w . f .1 ‘4' I r) :& ..C3 .5. Alt—11V}. 5‘.C-L:71r;-Cll L10 DUO}, ,‘C-fl‘: wiJ' lfllf'kl, i8..L-Q ,7”. (0.)" "" A " \ -‘ p ‘ 'v~ ~ I ,-‘ « N -f n. ‘ ‘0‘. L » 4- —: -\ J- ’ . , 1 €- 5 uC-nl) O..- 57. 4._L“..L’. 1. <-.L, .x_ g '.J’(- 1.1!. S. .91.]. COIN; 1-0m- .3 Colin: .L ' “ 4 ~ - ‘ \ \ -. - I ‘ . - —. - -_- ' ~ ~ w. - - l a- r- ‘ - - v ~ - , JLIIIC‘ i -CCWM'.’ 3“ 1.._C COCK, v... 9:1. 11 ‘ Lamb/4x ,5; ”5:41.;7 I SL111. .'_k» "v ‘J o 9 _ h .V ". q " _ _. 4 ‘ I "q.‘—.- ‘ ,, _ ‘. r ‘ _ A r' 1: - ‘ S‘DJI .1].ch 451- 1’1‘.‘C' \,:\.(i (ILL .LKJS“: 1" '...'g'\i./L L.'ei--l ;‘ ~k1;1t; (Jr. /.\’ ILJCCIO , V‘ " r " r 1 ~ ‘ IV": . .‘ ".- r" , ' . ' «1‘ . " u" ’ “ o ad:d. St,)*'uCl (JVY};2!LE|HT; .u1\»?1“ a; ;llTLLYW‘H . c.J.\; l)‘r,;<:. _, ‘ .‘. , ' . 4f- - .. _ ‘1~ ,: ,._, m 1 .-- ,. . . ._: 4 ’3 P.“ hjkr ”7.15 0* LL” gsmaJaxq CLJULCK L83 ¢one w*ph qu ‘~.Q-‘| 9 NI- 1? "fi r‘j‘ > -‘ ‘rl r fi».c> ‘ - f‘ n A h "- fi ‘2'- m.. 0, 3 m “,L. ;ne evheLol Layer was SuDaFauCO, -¢— 4.- 4.- , '1 r. - ..- .-1- .4-.. w ;: w“ _ .: ., ‘ 1-2.7 .r w: w UQECLOQ tfilCG’Ml u pwo ;,O—mi. Fer¢OLJ o; l)” LOm emu J— ‘- \vn.‘ . fl ‘ r- I“ I: »-~‘ . . 4‘ -' rs “ ~ I: .~ . 4- . u.pge mere COlenCC and Mc*.1ileh (combo rec .90 r) Wlpn \ a ‘ "f\ - . . a h Tr, a'1— ‘- .. W . ‘i J- r‘ u, r» 1 r~ p ./-_ j u V1 canalng a qun 00;):eo 01; p0 :e‘~rate ;rom A, .. ' rm 4.; - ,r‘ . 4V 1. . .- .- A 1 ‘ '..I .- 1 Jr atlcn. me laub : Lué pagan up in Utuer, QC¢€Q over A“ (“W ’\C‘ ' 7 v 0 19'71 " r- '3 ' 1mm t7- 1" hf" (~ 7n n" xr'x .' ‘f ‘ " 7" "‘ " 141' Tilda. Ll\/L)l\lnll fill—J. ~ 19 -.L1‘ x 1.9 e $.—O.L VUCLti A tz‘blo u CL 1—}. C2. _(_)LJC1L 1' hwl\.r.¢‘t ‘5 r f‘ If} 5' 1 PA " .t .1 ‘r n."- .t I - 1 Pc' (i -: (x-L- —: 1 lg ‘ eV:.‘ \.)..;1 0.; . c; Cxul ix COLO..CU 04-.-“. It.‘ 4 .9 ”etc (.JLOULJ. CO ' , . : " . "1'3 1 7. ."- ' ,, .W r’: ’:-’\ .<~ ‘ - 1 :Ln \fCl C‘QL‘O 37.1.5340 .L ) J J .C; Itc', . (k' . {3 \)1 7710 -.. .D/ o ‘17} O .2. E; Elf—Tn - r ‘- . q ' ‘ . ‘ -. -. ‘. ~ "" _' - r,‘ - O r v‘ . ‘L‘ ‘ D "' ‘~"n ybi;0. all on; 43' av 4‘y-¢20 5-4 mm. Live;abu;e value, 1 ’3 c' '1.“ '1‘ " I r’; \ o.p. l;o—*;/ /j m . Ec.. v. aux—f—o. ~— C... x. u .;. l O L 0.15 mole qu from 100 ml. of absciuue My of sodium 6th Hide was Prepared 61311513101 am; 3J5 g. 055 Sodium mots a I - "1' 4‘1‘ "‘ H " -: :‘Nv‘ ~—-i hr, ‘4' ‘ a k « .‘ r~ ~34 " “(l I v. 1 .“\ f. .' “- lo tum, LOU- - ..'. 4" (AIL-J- C--"w.1;.:...i,1.‘- 001A; uLOU V'GS C-‘vi-(lK-V— 4-9 ."'- 0 I j 1 l :- ‘ \ n 1‘ ~ _ r ,- _ 1 ‘ . '- 1 I" .4— - \00-1 1‘- T, r C)-- , 0 -l. ) K: ' In ' A‘ .P'L . )T‘) GHQ. 111: I“ (‘r Ulrlv] I - u ‘ N o ‘w vx“ P- ~ -' +- l ' \ 4 ~- ‘ ' 1 ' ’ + w u" a .L'u l.‘ ”137 flp'1-'_: k. -'_._.1_e( ~)-\)1 A4 ’1' ._'_( i "J (-1 G 'x: X .1; C‘ 3 u .1. VI”“ -:""~*1 -°--» : »-« Av\n: rw- -rn‘w~~' 7 rw.»«4»nr- (‘ F vnu n~ ¢(u»«rv ~ (.q ‘-\L‘« -,k \L ..-_L g1... Ln K _ C .I:‘...-.\" .L\‘_JL--\/_~ '.L-‘...'. -..A.‘~) 10’) ..'. s1. -‘.4‘~LJ‘I“. A.-4-~ W I 1 ‘ V I A h A j. 'I w x < '- ~ — l \ 4 ~— ~. fl — 4 (‘1 V -. w I - r‘ (‘ DOIJ—LLAK 1 1 k L) r ‘LOV ‘\‘L k» L'. ‘1- f) C\1.L..L... ‘ .. kal kit )1] 1 '_-r i .1. I ‘ ’ \_/ . w, . o , n "1 "\ P" ‘ [‘7 ‘ . _.-.‘n- . *1 of ‘- —~ ‘- 54 ‘ -- 4. ‘, - ,_ '14", .11. . fl . r‘ “V‘C‘ br‘fi ‘r— .. .,\4C4u3\- u u ...-»S L'uJ.lL--- LL” -v;,‘;c-.:,i-ll"0 _. )1 ,2.) 1.1.9. inn LLCLJUI‘ .‘ .. - .- ‘. .‘r' J- ‘_ . . - ‘ -' v} ’t f. . c > ._ . .: J- . - E r - I . r sq T Y); -'~. U -_ (4) ‘1 ( -—— kl ' 'W ‘,| . \JK-’ A -O :1— ' ' ¥-- Ik‘ :fli3‘-‘~:) \r Ti- L} ‘D .l- .L. S L1 :1. .1. .l— (1 n1 )n C‘ ‘ ‘C‘L 1 c c e W ,1 we *‘J" H 0 ’4 ‘J-V -.- -‘- U “L‘uUL ' ( \LuC .LJ CirKlE‘k 2.1;) - . .'- - .'- ‘ -' .4 7 4 - I" .’ \ . f‘ .. 4.- f‘ .1. I“ 7 "C " 5" n _ ‘\ 7‘ r SO.--L(.—U: -02" ‘>-\-~\.- C4..\/.L («C LOC 1-1- ‘11; \I-.'O 1“.)\/—:AAJ_. :30; " ’I—IS OJ. A'LJ.L(3I‘. 4' - T . e. " 7f " ' fl .1 ' . o; a rxemuxfi1<3renge COiClTWL.LlQLLid. Imzcxgxxmzs DOPplOO. . . . ..—. ,e - .1- .— .'- ,‘ ,1 + 1. "‘3 I" ' .4- - " ‘ w ‘ ‘ y‘ ‘2 ,4. - ' ‘ .J 4. use C(nvunpchuu uO L&;¢ :es VOLdJQ emf 01ers 3.0 L;uh . 9 "‘ ‘ ‘ 0: fl "‘1 ‘ " .‘ ‘ "fi - . ‘— P‘ r:‘ ‘ tune: no oni°¢r eneun .: L.O L1. 0* 1;: 011; DfOudCL. f t‘ ' ‘ ' 4"] ' _ ‘ _ I'\ J” :;0 CO 3;neu Drouuct was lrng ion: ,/ '3 ’-‘ _.'1 ‘ ‘I l‘ I I J— I‘ r: ".‘I ’ ‘ 1 : ’- J- ‘ v.‘ r A 4- ~ 0.) f. o 0... 1:1,; LK'C~CK,V\L C: O._\):C€ C‘lkt.C}1.:-”O.e C‘AKJIU1&:’-LE‘.UQA:LIal. quel acet.i was umdis+il;ao'e even at a tenuerature O A . o 1 y“ . 1 1 — Fl 0 H‘ :x" ‘r~r”f‘::\r' «T- :‘l (:1 "f‘ 2 32-JJ-'.“4 Vls J¥l . \‘4‘ ‘ *-/ )Cn/QOItr, K114 k1...~elfl. - QJJ-.L J.\‘.e 4A ' \____.___ 6“ “If ht: ~ 1:; I “Pu—u) 2"U1. (( ~21. 3’) ‘- (f: .2 / v" r) K, {E} C 7 v \ - "n ’V 11 ' 7a 4 -. ’ -r v- 1 4‘. ‘ . .4." , ‘ ~‘n _--L k’ L; ‘L .. . " 'I ‘ a- ‘4 1‘ :: “() .11 v .7 F‘ r. u ‘f- — t‘. L“ n (\ja ".n C x " l'A-.. L¢U A, L; .g; \1(;' o—' ‘ ,~- s v —~'-04 r7 . -- i— r- 7“ .1 . 0-; SC. -L 1- 1.1 ‘ .KH ll:.__ 1-1 JC' 1:- \- - 1 AJ- a- 1‘0- lLk \J \J (:1 r :2; O “-1.1 ”\J :L O ’\ ,\ -\ r\ ‘ ‘ /\ vx‘ "~ 3« _' l ' ( ‘ » J " " O;-\o U‘ k _‘_ .., J .J E”. \(‘)..LI-’l/ . .U ' ‘- 7'\ A‘ ’3 I V x (u -y_ 3’. —Y I 3 .‘l ‘ ‘ ’ r ” 'I ‘.I.....’. I/;L (ALL. ‘J. - s.)LJ..‘. w \._J- \' “ha. I -| 0(? f, “.1 ‘I E 1'“. ' "“ 1,— ’ 1\ ~ I . ‘ Ck)\)...v . '.L(z\, UC\\J.1 L-J-Ll .1. J p... ('7‘ '4" -‘ V. f” 'fl‘ ' ‘ a": r. )\/...--L.L ‘5!L«..4 .’ |-.(...~, - '2 -' '3 h .’.t«) ‘..- {v- 1‘14. Ck. . , ; : n . ,., 7 76 K)k CtlJ-‘JAs :JK/J- (’1 C ' ' " f _ I‘ i ‘ . T' \ ‘1‘. .L.\) / I '\_/ _,O l.’ A- stildaryde diczly‘9C311l .-3 .33-; -lgh f f 1rnnpl, causing the Li; $39 no Lake on a id co;orafion. ' \ ' .e;1 33M} ac; La" TC<1 b.111 81? ed, e>c,er?h;l “ep3ved cm. the veactio“ Slash was set a ide roog triberatu“e. It gas than kept at its re f r 4 hrs., and tks alcouol was removnd in a 033“ r to yield 38 g. of Q r~d colo :c d liquid “r'c io1ction of tfiis in VQCLzo gave 9.2 g. of stprting materials. Jhe residual product cou r‘". 5 3. n-Jq.‘ ~ r\-L- r. LAivuwfi r - . “(\l O I" r-. ‘foC-llA-ll QlS‘JliLed Cl L- C» pc..1§3‘l"«;:uL.I e O .._\/O gnu ‘ “"7. sure. 0 '3 j, - "\ 4-K; ,-‘J-‘..' " ~ 1 u-,- 131120 1.. .1] 1,--lz,-1;rl1,.;1.o gl ycolic £1010 L. ' 1,11,; 1" k. - n l) l 0.1 I I; :D f”, o clcomol. .CLC CC. , 3.11 .too 23010] ’i 0 turn a - A.— ~.'.. ha 3 f. If;A.L’ MD ‘J 1&4, .- 1’31 . An\a 73:10. (J- 1‘] _. f s / ,_ \_’A.- ‘A. v‘ 1 ~. g} ‘ U0 )1- ",'n 9‘ ‘A \z’.' 3-?0 T r~, L C 7. (xv/‘7. 0U. l u A I 1(' 177155 ' L rm \1 3. \J ‘It’ufj .1- 4‘- \1 \‘...¢ ~'. ~r+ ., A ‘1’ a d‘-"C‘ \I..£k) O 1‘ .‘ -fl;_. {.2le 1.13- q l —. -. (NV-A f‘ .L .k - £11 - a i no. .7 5. no 7’ h .ic \ '30 ICELTJO 1" . 3.1 -LVEQ.‘ t}. I O -. 1. .‘ C1 --.+-- . .'— -. " €4.\Jr‘\'/\CKJL.O. A ET 3"- 1‘) Tféllfl L I '~ -»,n .. (A y-‘q'u-<« ' .JJLLI' Q. _ -n '1.,"_] F‘ \/ \JC- U.L.t_/ -L< '-"I~1. (H 1" .LLJ toL.Q .,- .'_. -1- vovreg 1Q .1 7* C .C 3. .Lej‘ '9 a1 (0.1 m g). '7 111C ’\ I A w 101 d 25 53 y en 1.1 nlace A ”I -L W .L 2‘5) 'c‘“ v q A‘.‘ \J \ ‘— :1 81" was 9. (p 4:10 L 'TL'S‘T/ Q A / ¢ ‘5‘ Up; u—y-m .L L. ”V M -L“J ‘ t!“ .11 L—V c‘ [.1 '-~. [I r‘ 2 ’.'; "\ " fl 4"“: ._l - , I" . _ ‘ 0i 4, '1‘? inJv-J -Q maul italtlfl ““4: 1e 11;:0lvca 1n '1 J_ ‘ r. esxytgczfi“:c: TGIHZLlCL; :1u331117cl t153 STJQPQBTLIfllffifljTC Icas 1. 1- .: .. WM: s"-.. c: 7-... ,..3 ‘1" --1 - .' - . £188 ‘uEIki cut Eu) lOl‘ ,-' Ilfw. Evin CllOUz-fff- CO COUJ. IO POOH 'c blzcx cvruny r11twuor"t 6C1Q - ‘ . . - u \ o ‘ - u") ‘ ‘,' ‘ ”~' - ' ~. I'\ - n ' ‘ -_ a . ~ , . . ‘ V - - --\ —- v‘ _ - v 4- :- 1u-s rwxXTVcc [u-.111t:cdhg:c Lll,colv121ora. ;“0 catalyst, 1.34 ml. (O.bl§ mole) o: anhydrous stangic caloricc, was \1 (t r—J H 0—4 8 m 91 F.) 1,- O a, ('D r )_ C O l .1 , fl_( - fi"_:_. ,= n . ‘ v; aaaea wlt” a uJSlhfc. he reaction #4 H, -- ., ,. q J 9 .- 1“ .- - . .3--‘.°. "a m to room fiumparatur ant lelt, filth 0c calcull anaxldg 9 M .1 .2‘ rs ,A .t- r ‘. A A f . (J a . I *4. i nA- r (A. 1 COO OV “{- r/‘l ‘_ ‘... Uho 01‘ A UK: .n- J. Lg. k/-'L J_w —.- o -. . ~— T L I £50 171141 “31 d1 J. r r ‘ ed p07C‘ over rotag‘ fih (4;; 7'.\;: L; b'I *O‘v‘vl H O V l . - A— ”— Y r‘ (x c‘ 4- U .0? ‘ h 1 I") (‘ ried .Q d -I . . :1; LI ( Q J. rr1: u \1 (.5. C p 1 ‘th.’ a U r. J. MK. 'J i .L I“ ‘ . U \4,, 'V O . ‘ fl .‘ A") f? C DO 1 ,1“: k l 8&51 C n -rf‘. 1 (WW (‘. e (_‘ \ . i.) L; u 1 -or L0 1" letter (3* L. O ”flu N ‘. CA ;‘L;i lOII ‘ct' ,V T8“ d J I .r, ‘ -‘ scir A ‘7'} .L- ‘._ LII l :11}: ‘3‘ .. (1' ’. ¥_. ‘ “e“ \l , s. a '1 | , live- '113n I (A 1 iv £10 ?8 r-\~ Lg "7710 al 0x03} J. 4- lnl g.o \ V I Q "sturg .. n,‘ C \) . -.~' .' \Vl ’\IJI1 Ll}C -‘ l I“\ -(~ V ,+‘ 3313 #3 and cooled to room temperature. The black syrupy phosphoric acid was filtered from the benzene solution, lele dis- solved in 150 ml. of water and extracted with benzene. The extract and initial benzene filtrate were combined, washed twice with 5% aqueous Na2003 and then with water until neutral (litmus paper). It was dried over calcium chloride and't ( benzene was removed in a Rinco evaporator lcaving approximately 10 ml. of a red colored liquid, which ccrld not be crystallized. An attempted distillition at 165° at 2 mm. gave only a few drops of material collecting in the distillation head, which'solidified on cooling and had a melting point of 56-580. As the distillation flask cooled, additional yellow crystalline material formed in various upper parts of the silask. Thus, residue in the flask was warmed on the steam bath with a small volume of methyl alcohol, treated with norite, filtered and concentrated on the steam bath while a stream of air was blown into the flask. When the volume . had been reduced to 7-8 ml., the alcohol became cloudy. . On cooling this solution to room temperature, it soon deposited a yellowish-white crystalline material. This was collected by filtration and dried to obtain 0.9 g. (0.00474 mole; 21.2%) of product that had a melting point of 61.20. Literature value, m.p. 61.0-61.50 (12). Ah A second attempt to obtain this product, using stannic chloride as the cyclization catalyst in place of phOSphoric acid failed. N-Methylformanilide 10H} ' ‘czo H In a three liter flask equipped for azeotropic distillation, was placed 321 g. (3.0 mole) of N-methyl- aniline, 300 g. 90% aqueous formic acid solution and l¢00 ml. of toluene. The reaction mixture was heated at 8h° to initiate the azeotropic distillation and was continued until the temperature of the distillate (in ‘the distillation head) reached 108°, at which point 1,325 ml. of toluene and 159 ml. of water had been collected. The remainder of the toluene was removed under reduced pressure and the product was distilled in vacuo with the . fraction boiling between 112-1160 at 8 mm. being collected as pure product. It had a refractive index (29°) of 1.5532-l.5559. Literature Value, b.p. 114-121 at 8 mm. nB9 1.553-1.555 (30). 45 2éBenzo[thhienylaldehyde S 0:0 H A 20 g. (O.lh9 mole) quantity of benzo[b]thio;nene was metalated wit? freshly prepared n-butyl lithium in an ether medium. . To the cold, stirred solution of 2-benzofo] thienyl lithium, was slowly added, 20 g. (O.lh9 mole) of N-methyl- formanilide. The reaction mixture was heated at its reflux temperature for 5 hours. and hydrolyfied by pouring it into 80 ml. of cold 3 N HCl.- The colored ether layer was separated and the aqueous phase was extracted twice with ether and these extracts were combined with the ether phase. The ether solution was washed thrice with lOO-ml. portions of l N HCl, once with 200 ml. of 10% a,ueous NaECO3, dried over magnesium sulfate and the ether was removed in a Rinco evaporator. The residue was diluted , with a Small volume of 95% ethyl alcohol and 125 ml. of saturated sodium bifulfite and set aside fer 10 min. to insure complete precipitation. The biSulfite addition compound was recovered by filtration and washed with ether. . l The aldehyde was regenerated by treating an aqueous #6 solution of the bisulfite addition product with an excess of saturated Na2003, and setting it aside overnight at 0°. The precipitated aldehyde was collected by filtration and dried in a vacuum dessicator to obtain 16.6 g. (0.101 mole, 68%) of product melting at 32.0-32.50. Literature value, m.n. 34.0-3u.5° (31). . 5(2-Benzo [b] thi . 'nylidene) rhodanine ©ulW 0-. In a 50 ml. flask fitted with reflux condenser, 4. 0 g. (0.03 mole) of rhodanine and 7.5 g. (0.09 mole) of fused anhydrous sodium acetate was dist lved in 30 ml. of ‘glacial acetic acid by heating the latter. A 4.86 g. (0.03 mole) quantity of 2-benzo[b]thienylaldehyde was added to the hot acid solution. In approximately 15 minutes, the rhodanine derivative began to precipitate , and the acetic acid solution was poured into one liter of cold water. The reddish orange colored crystals were recovered by filtration and dried in a vacuum dessicator. The product weighed 6.7 g. (0.02h2 mole, 80.6%). After three recrystallizations from 95% ethanol it melted at 286-287°, #7 final. CalC'do for 012H7N083: C, 51.96; H, 2051+; 8,3bofJf). Found: C, 51.88; H, 2.76; S, 3h.80. Sodium salt of 5(2-Bu zo[b]thienylidene) rhodanine ' \/ (In a 250 ml. beaker, cooled go 00 by an ice-salt bath, and equipped with magnetic stirrer, was pkzced l g. (0.00362 mole) of the rhodanine derivative. To this was added 100 ml. of water and ll ml. of 5% aqueous NaOH. After stirring the alkaline solution for 20 min., the sodium salt was removed by filtra1ion and used_dir- ‘ectly in the preparation of JLmercaptoqa-(Z-benZOLBI thienyl) acrylic acid. JEMercaptoqs-(Z-benzo[b]thienyl) acrylic acid .H CZC-COOH . .3 SH The sodium of the l g. of 5(2-benzofb1thienyl- ~ ifene) rhodanine was added to one liter three necked L8 flask containing 350 ml. of water and #0 ml. of 5% aqueous EaOH. The stirred alkaline solution was heated on a steam bath to 75-850 for 0.5 hrs., rapidly cooled to 250 and filtered through a norite pad into a two liter beaker. A A0 ml. volume of 3 N HCl was added rapidly to the stirred filtrate. 'A flocculent precipitate separated; This was collec‘ed by filtration and weighed 0.275 g. (0.000862 mole, 32.2%). It melted at 21h-2160 after a single recrystallization from chloroform. A second preparation of this p oduct was carried out with an improved yield (63$. (“2, t-Dinitrothio henoxy] ~13— (2-benzoflb1thienyl§ acrylic acid N02 / ) ,coon //C\S \ / N02 C S H A solution pr pared from 0.34 g. (0.0017 mole) of 2,t-dinitrochlorobenzene and 100 ml. of ethyl alcohol was added to a 250 ml. round bottom flask containing 0.h g. (0.0017 mole) of.i-mercaptoqa-(2-benzofb]thienyl) acrylic acid dissolved in a small volume of warm absolute ethanol. A 1.5 ml. volume of lO§o aqueous NaOH wa551dded and the alkaline solution was heated at its reflux tem- perature on a steam bath for 50 min., cooled to room 1+9 temperature, acidified with 2 N HCl (congo rei paper) which caused a yellow solid to precipitate. This was recovered by filtration and recrystallf;ation from absolute ethanol gave a yellow crystalline solid in the form of needles which melted above 297°. fingl,’ Calc'd. for Cl7HlON2068: C, £9.48; H, 2.57. Found. C, 50.5h; H, 2.71. Thieno[3,2-b]benzo[b]thiophene-Z-carboxylic acid Iodine, 4.0 g. (0.01575 mole), was added to 100 ml.. of absolute ethanol in a 250 ml. flask. To the iodine ‘solution, 1.9 g. (0.00805 mole) of {Emercaptoqfi~(2-benzo [b]thienyl) acrylic acid was added and the reaction solution was kept at its reflux temperature on a steam bath for 2.5 hrs. and set aside, at room temperature, for #5 hrs. It was then poured into two liters of water and excess iodine was destroyed with a saturated sodium bisulfite solution. A very dark green colored precipitate was ~ collected by vacuum filtration. This material could not be recrystallized from any available solvent nor could it de oxidized to t.e desired thiophene carhixylic acid deriv— atiy' by potassium permangate in varying concentrations of NaOH. In a second attem,ted preparation of this material, a 50 ml. flask equipped with condenser, was charged with 0.9 g. (0.00381 mole) of'dLmeroeptoea—(:-benzo[t]thienyl) arifilic acid.and 1.93 5. (0.00762 mole of iodine dissolved in 30 ml. of dioxane. After heating the reaction mixture on a stern bath for 2h hrs., it was poured into two liters of water and a saturated sodium bisulfi“c “olution was added to destroy excess iodine. However, the solution retained a dark brown coloration.- On acidification of this solution (congo red paper) with concentrated HCl, it precipitated a brown colored solid. “The latter was insoluble in all concentrations of alkalie. In a third attempted preparation of this compound, ‘3.6 g. (0.0152 mole) of the demercapto acid was dissolved in 400 ml. of dioxane and 7.72 g. (0.032 mole) of iodine. was added to the solution. It was set aside, at room temperat re, and two ml. samples were taken daily for 12 days and tested for ring closure product. No product . was isolated during that time. At the end of that period, the remainder of the solution was poured into water and decolorized with bisulfite, to yield only the starting émercapto acid. 51 In a final attempt to obtain the thienobenzofb] thiOphene carboxylic acid, 4.0 Q. (0.0158 mole) of iodine was added to 30 ml. of nitrobenzene and the latter was heated to 197: at which point 0.52 g. (0.0322 mole) of dLmercaptofifl-(B-benzo[b]thienyl) acrylic acid was quickly aided to the iodine : lr‘ion. ‘he,reaction mix- ture was stirred rapidly for one minute, quickly cooled to 300 and extracted with 10S NaOH. This resultrd in the formation of a bright orange colored mixture in which it was very difficult to detect ohe liquid—liquid interface. 0n acidification of the alkaline phase with cone. HCl a slack powdery material precipitated. It was recov- ered by filtration and dried. It had no definite melting point up to 297°. When heated in an oven for a short .time at 110°, it gave off dense iodine vapors. It was insoluble in verious concentrations of dium hydroxide. l-Carboxy-Z—(2'—benzo[b]thienyl) ethylene disulfide (Q! l 2:?) A 0.9 g (0.0038 mole) quantity of {emercaptoefi-(Z- benzofblthienyl) acrylic acid was dissolved in a minimum volume of absolute ethanol and cooled, in a small flask, 52 to 0°. To this stirred solution, one g. (3.0039 mole) of iodine was i ied. The reaction flask was main‘ained at -15 to 0° for 3.5 hrs. during which time no precipitate formed. The reaction was set aside for 26 hrs., at room temperature, but it failed to yield any disulfide after decolorization with sodiun bisulfioe. s In a second attempt to prepare this disulfi e, a 250 m3. beaker, cooled to 0° (ice-salt bath), and supported over a magnetic stirrer was charged with 0.A g. (0.0017 mole) of the demarcaptO'acid was‘dissolved in a minimum volume of abs: ute ethniol. Bromine, 0.188 ml. (0.00l7 mole), was added with a syringe to the stirred alcohol so- lution. After 1.5 hrs., no disulfide had formed as indicated ‘by its lack of precipitation. It was poured into 600 ml. of cold water and the solution turned yellow but the disulfide product could not be isolated. In a final attempt to prepare the disulfide, the procedure juSt described was repeated using a 1:1 ab- solute ethanol-dioxane mixture and iodine as the oxidizing agent. After keeping the reaction mixture at 0° for 1.5 hrs., no precipitate had formed. Pouring the mix ure into cold water resulte? in the rrecipitation of the starting d}wircanto acid as shown by its m.p. (212-2140). 53 3-Benzo[b}thienyl carboxylic acid I a --000H \ J A one liter three necked flask equipped with a re lux 1 corienser (drying tube), mechanical stirrer an. dropping L" funnel was charged with 3.35 g. (0.22 g. atoms) oi magnesium chips and the latter were COVCT€d with 200 ml. of dry ether. 3-Bromobenzo[b1thi0phenc, hh.2 g. (0.198 mole}, was dissolved in 50 ml. of ether and several ml. of tfiix soluti"1 was added to the reaction flack. It was necessary to use a methyl Grignard to initiate the reaction.- The 3-bromobenzo[b]thi0phene was then added rapidly so as to maintain-Spontaneous refluxing of the ‘recction solution. After the haloheterocyclic had been added, the mixture was kept at its reflux temperature for 2 hrs. and then dry carbon dioxide was bubbled into the etheral solution for #5 min. This caused a thick brown oil to separate from solution. It was then poured into an ether-dry ice solution hid hydrolyzed with 3 N ECl. The etLer layer was separated and the aqueous portion was extracted with ether, combined with the ether layer and dried over magnesium sulfate. 54 The ether tas removed in a rotary evaporator leaving 32.5 g. of an itiure yellvv colored solid. .This was dissol Cd in 150 ml. of 33% aqueous haOh, diluted with wa er to 3_3 ml., throughly stirred and filtered to re- move insoluble materials. The basic solution was acidified withsconcentrated Ltl, extracted with ether, dried and the ether was re- moved in a rote y evaporator. (The product was recrystallized from a 1:1 ethyl alcohol-water mixture and melted at 172°. Literature \ value, m.p. 174-1750. (32). 3-Benzo[b]thienyl acid chloride /\l \l \ s A 10 g. (0.0562 mole) quantity of 3-benzoLojthienyl carboxylic acid was placed in a 100 ml. flask and A0 g. of thionyl chloride was added to it. The reaction mix- ture was warmed on a steam bath to effect solution and then brought to its reflux temperature and kept there for 1.25 hrs. Excess thionyl chloride was removed by vacuum 's‘illation and the product was distilled under reduC'd V '— O 55 pressure to yield 10.6 g. (0.05Ll mole, 96.A%) of acid chloride melting at 49—500. Literature value, m.p. 500 (32). Attempted Preparation of 3-Benzo{b]thi0phene carjoxaldehyde 1 S In a 500 1’. three necked flask eqripped with mechanical stirrrr, re“lux condenser (with dryih: tube) and dropping funnel w:s placed 5.8 g. (0.0448 mole) of 3-benzofb}thienyl acid chl ride dis olved in 155 ml. of dry diglyme. The stiriad solutior was cooled to -730 2 prouanol-drj ice) .and L; o 41. ’0 ' +3 mc e) of lithium alumino—tri-t-butoxy hydride dissolved in 50 m1. of dry diglyme was added during a 45 min. period while dry ice was added intermittedly to maintain a temperature of ~72 to -730. Following the add’tion of the reducing agent, the well stirred reaction. mixutre was allowed to warm to room temperature (1 hr.), poured into 500 g. of crushed ice in water and set aside overnight. A white solid precipitated which proved quite difficult to filter. It was insoluble in ether, acetone and 95% ethanol. An attempted bisulfite addition competnd of tne solid gave no product. \Ji 0\ 5(l—Penzy1aoine) rhodanine S i 700 ml. volume of glacial acetic acid containing 3 06.) g. (0.5 mole) of rhodanine and 123 g. (1.5 mole) of fus>i an ydleus sodium acetate was placed ii a .ii' flask. The mix'ure was warmed to cf act saltcion and 53.0 g. (0.5 mole) of benzaldehy e was added in portions with interni tent rhaiing of the.solut on. When the aldehyde had been added the reaction mixture was heated to just glow its reflux temperature and kept there for 0.75 hrs.' It was poured into five liters of distilled 'atcr and the resulting yellow colored precipitate was \ recovered by filtratiOJ. It melted at 206-2070. Lit- erature 'alue, n.p. QCh-ZOSO (20). d-Mercaptocinnamic acid , H C:C-COOK SH A 74.0 g. (0.34 mole) quantity of 5(l-benzyladine) rhodanine was placed in two liters of stirred, warm (60- 650) W"’3r and 54 a. of NaOH dissolved in 500 ml. of water 57 was added. After stirring the alkaline solution for L5 min. at 60-650, it was co& of distilled water. 0 the slightly warmed alwaline solution Has added 3.3 g. (0.0206 mole) of fi-naphthalene- thiol. After cooling the sodiumA3-naphthalenethiolate solution to room temperature, 2.85 g. (0.03 mole) of trimethylene chlorohydri“ was added to it rapidly from a dropping finnel. The stirred reaction mixture was heated at it; refluv ttapcrature for 3.5 hr:. during wbiCh tire a broth colored oil separated from solutioa. 0n cooling the solutioa to room tonneratur the oil solidifie . It was col acted ‘y filtration and dried in a vacuum d ssicator to yield 3.90 g. (0.0179 mole, 87$) o” product. This was recrystallizedsdrom a large volume of petroleum ether in the form of whit- crystals which mvlted at 620. _____~_l. Calc'd. fOI‘ CLBHlLOS: C, 71.52; H, 6.46; S, 111,069. ' 3:3'-Thisnaphthoxy-n-propyl-p-nitrobenzoate ‘ AG S-CITZ—CHZ-Chz—O-g / I K/ I / \ :02 This compound was prepared by the method described by Strainer, Fusrn ar.r7 Cartin (35). A single recrys- tallization f;om ausolute ethanol gave a or duct melting at 92—1000. E~£'-Thionaphthoxy-n-propyl-Z,u—dinitrobenzoate h s'ngle recrys t .lizzetion from absolute ethanol pave a product with a melti nq point of ll5-1l7‘. 13—Hydroxy-n-pr0pyl—6”-naphthyl sulfide / I“: ‘ / , \rs-c172_ —:—3 for: . 2 C 3 \ 1! - L<§§>//f\\\///' An 0.8 g. (T.005 mole) quantityr ffiknapht}-al ene- t.iol was disgolved fn 5) m1. of.wzter containing 0.7 Q. (0.0057 mole) of sodi11n1 hydroxide. To this alkaljpé solut on was *_ded 0.55 g. (0.066 mole) o' pxdpylene ch‘ ro Idr n. The react; 1 mixture was heated at its reflu: pamperature f.or 1. 6 hrs. cuiLng which time an .1. .n;oluble ail precipitated from solution. 0n cooling, it solidified and was reroved by fi tration to yield 0.7 'a of product (0.00321 mole, 64. 2%). Recrystallization of this material from k1 M1 eum ether gave a product with a :elting point of 46 5-L7. 5O Anel. Calc‘d. for leHlAOSZ C, 71.52; H, 6.A6; S, lilac/)9. Fcund: C, 71.61; H, 6.59; S, lh.5t. 3i. material was prepared as previous:y described (35 \ I Alyy-Thionaphthoxr-isopropyl-p-nitrobenznate v I /\;i \S—Ci‘r; -- -".-O- (, L\\\>//,% This consoLro was preprred oy proc durcs pr;v;ously 3 described in the 1iterature(35). A single recrystallization fron assolu.e e,11anol gave a product with a melting point ‘ v. 1‘ I -: I q - -' - -- A Jlkd. . I~ -uf. conrr‘..03 fiYinx.1Aioe), aJeczw11ic—aL Lti.un r ; fi,- - “. ~ _ : ., .,. .. 4.4-, 1- ..-_ ‘ . -1. r 1. -: -. (Alix f'lc'lI‘ailql LlL'-,'c’zl":,z COIl;;C-;Co_:-.'z;) JOEL»? Ill. ,0" Wild; c. CUTOUT»; t4. " \ , 1 .Jb ‘ ' 4 -:--~_ Vvl‘ 1_,. 3" -v.- I' ,. '3‘ .LUMLCJ. RUG. 1'11 bI‘OfiCfl LCS .1.L.'.LC'L-I'c..‘3 CI L«lflé::’:\.i filo“ . .1; E). (Oofil- .. ,_ . .1 . ,. ,,. - . ~ ..2 I. , w .0 ,‘. - i.- 1. - 6. atom) 01 mabnosium an. covered alt; 150 ml. oi cry atncr. 'W 4, .fl .p.‘ I ‘...‘ ;\ -' ‘ K‘.‘ r " .5. ‘ I . ~r -‘ . °(-..,1o..1ona .1..‘-,--ale.1e, c9..- ‘ . (\.-.3 mole), was 0185.0:LveC. in 1.0 ‘ j on.x.€ls ackl-c O 1‘" £1 .9 43‘ n ‘ 1-.?-_ ,. 1 _-‘. ° ml. Oi et;er .n0223015 one tuird of ollfi s -1~., 4.‘ _,- ; .5--. - -. -. .. . .i*ectly to tie er- ~2esiun aintire. A One ml. Guan- .. - .. - p -‘ , - ,: _- 1 .. ,. *- ‘ ‘- 1-. .. i .: ._ L11 217‘ O... in‘nL1’11l j,()\._'_(.’3 ”(th FC..(.€C~ 1’0 tIA\/ r? CkCt—On r-:.J. :U1llfle r J ,' J. . v - .. J— -.: ' a .f.‘ . 7" ,~< . . rr - ‘7 HA”; lb 8 1’48. .37C (.0 -LpS felllt-.. Le..~.7‘a:“ik"u‘zli‘e for 800111; one D - 1 ' ‘-‘.. -. - -.-~_ (“'- 1‘ " A . x '_ fl _ ‘ o _ o _ ai1ute to inl’iate tne .ea actio,. hit I tne ini tial re actio1 ~vr\ - - {-1 fl 4- .i ‘r- 35hr 1 -. e, ' -n f D 1 \"\ )\l‘ .1 "\l‘ mu: Ulla? control, tne .anai1cel oi the JGblOmOnert ouene sOlution was aLcea to tne stirred reaction mixt_re at a r‘ 1 fi.." 4 ' -‘- ”1“: 4- " -. ‘ I". . a - . 1 - ‘r 'V- v rate sullicient to na_rta-n a Vigorous Iaflui 01 c . : .. , 1° 13.0. . a“: -. - IT...“ -3; 1 .“cactic. .1ceia. alter anoine the aromatic ole ice, tne “ - - 7 . f‘ *..'r‘ ‘\Y‘ . ‘- '1 ; r 4") -.w - fl -' fiiLDCJJ e wens WEITKXJ in c.\»a1t.1£1tel cudd1 i . --1u:li Inc. during which time the Grignard mixtur c becere cuite thick. I. '1 .l I ‘ f v. f'\ r: h ‘. 7' . P. — Y.'r I" l‘ ' 111; [1.1.8 p01. t’, 900 £~O (klOJ (C... (TIOAES) OJ. SLILlJ.‘.l.r~ 'INC'C: C(Sdl- ‘ O tionslv ended.rnjuh3r'ry ritr1fien'war "afidiy svent through the reaction flask. Ike addition s; tre sulfur caused the reaction nelia to set. aneouslv rejLux and markedly lowerid the viscositr 05 the reac ”on solu ion. It was aeain 1m-ka fit its ref r te—rzyierature ior an ace ditiOIV l T‘ ‘3 f' Q 1 . . _ _ - . 1 - , .' _.. .3 , 1 r. _ , - _ - - --. nod: during wnich it a sin OBCQL; ouite r ctr in '-_,‘ _) . I} consistency. The Grigrird cc slex was hy."ol zed by q 0 ~ 5 W q, 1_..-~ ‘ O - .".. ‘7 'I: ’V‘ fl . -: 1. . ‘ I . . ‘ .~ aw>r .ltl-;l poti.igm 1%,, .thli VJJVOZCTIS ,-. -lfHL, into Cof!.1l. I O J ‘3 .1 .3 J —r “l f" -v t '\ . -. -. ~ ‘- :- r I e 4—: . ‘, ~ c ~p . .' .C‘A. «u...(,‘_L]_‘L‘-_;.i « «1.0-1. x: 1.0111 on. me 1.4.” 0.1.;33... u“.; ,‘I ~ " .‘n »./~ I .. -r-— v~ -. . - . uJ- c- --. ,- ~ I - -I r‘. SOlhulO? Mum Daub ucllHiLUlV .CiClC and LoCcM Ulhciiizu . ‘,\J‘ _l .-: fir — J‘- "-.(-‘ - .4 ‘v. (.4»- 1 1. A _. , ,. J L ALL, ‘ .LAA. V / .A--..k'QA \) (\IJ. ‘-_§.i_k) \IAJ .. I. ’1 ..K.\.‘L L):/ (:41 CO :LJ. ’30 K’CC’ O L‘AO ‘ .3 -1. 5' O. 7 ,- J- A .3. - (a. .1- v I 4.. .' .4- ’. ‘ ' 7 _ I ‘ n . "‘ r: ’ Wr’ n F . . "fi'\ ”5 . '~ I A -1, !~ ‘ (1.1.KJLl-LAL \ ‘J\' 1"L k.’ \145ULCCUC‘r-J 'lb ‘~/‘\l.' __ ’ (‘L .L.CC . \J... ' .A'II‘ ' I'I'D..J.:- ‘( (u ‘ ‘ 1‘ 1 (‘h .t r J— -~‘} 1- 7.“ ~ In“ 1 '1 \g -' 1‘ v, in ( t1 K, \1 LIL - | L)\ -1\~ 11. ; \ U;A\,3. I4 0 .L KIA AOVOKL *n C“ A .1. .CO I: ‘5 1“" 4‘ ‘1 I. . r‘J— J .1 ' P;-‘— -T f‘ 4;} + l, a r‘ (V: I“ 0" l A. 1 "-7 F... ‘ j 4" I, €Vc~oic “u. 3. . u- .. .L 4:. L. Jr]. OJ. u..\3 .'K'.‘u_'_.u.Llci 04.1 JJJJJ- ‘LQ one u ' . 1 - ‘ J‘ ‘ ‘ V ‘ "O ‘ ~ . 4 J. 1 '\ 'v‘i‘fi ~v) ' ~ ‘- ‘_- .y > -- . r3 0 -4< ( .i 1 «VA ' - -, .ffi- ‘ r.‘ nu... V A‘AKJ-n C s OleA 1‘) lAAgbA“ UOi-A x .. (A k, l\’/‘ l. I --‘L. 1.1-- LJCJ (Irv Ulkrv iulte, b.o. 105—;C20/1.5 n1. (32). (711° .1. .. .,- ,)..,,.,4 3‘ ‘ ‘ P... 1315 comuourc .; >10 u3cc using tne orocecure cm- ‘1 "' v ‘ ~ ' v r ‘4 I" -- w . . 4 . -‘- -‘ t.) '3 r‘. 1‘4! 1’ w f ~ I» q‘ rl‘." deOT'OQ 1n ti- {'3 SjlebAIC‘1bl\. OJ 1L C. p-AIGDAAUILjrl Ckl’lC.1.J.\)\g;ueo 1.18 ' J. r. f‘ -«~. rs \ 4-. nr .1 ',~ I: \A — . ’ ;.I’lt €1L.Cti(‘rn Oi 3.7 3.1. (c.0133 molu, Oi 06.1.4 IL.L.1CLlLil€‘ o11.;Ol ‘ .\ ~- A I“ w l f“) k . "5 -“‘n . -0 - o ‘ A use L.K i. 3.C.:) mole) Ol16~UlDOlel b g :3 H O }; O ’"J I-“ :1 (D . fi“ I. 'Q 9. \ 4‘ ‘r‘l *. 1-l I'} i - ‘ . I. J— 1' lu/ x,leO-lt ir.. .M;sic Neale” Ml tio :1 oi t.K3 e0 "w «w' r '~—n - 1 4— 1» 1 1- 4: 14. Cil' allfiO cm. 1.0 convelsion toza “yoroculorioe salt yielded #04 8o (v.0lL3_mole, 62.5%) of the expectecp Droo- uct. After rccr s ellizat on from isonropyl alcohol, the bro “ufi;;:cf.el 8:,31g;,5_183.750. .J \ O‘. o \J) N \) I I\) O “rel. Calc'd. f0: Clyflz :lNS: C, S, 10342. Loun‘: C, to. 6; H, 7.32; 3, .).lo. ' -' v . ‘ - , \~~- ~ r‘-, ~ -'- ‘ v ‘ 1 ~'-.. M 7- v 13. ’~ - 5 ;‘ ’41J10“'1-rn7J‘X,l-@£*fk.plutfljfiL snx-uai0 .9 .w- I - (11".. .v ,- _‘r‘- J- J iorfi on algali lileUJlO oily 6min . 1.us MOS MLur&CbLU 0"}; “ \J' "L. ” "’-' ““.: ‘1 " ‘3 r " ‘ ‘\' 41 7 C‘“!' \r--' r1v'f r W F ~l‘ K"..A “ (J? l\-.’ K... .. (1.4, J. .|.. O’t'l~}¢ £:( A,;;l~ L‘..._L151 kl L-J..L(-"oll~(:‘. J.A'. [Ir/.L’ ‘4‘1t‘J P +h~ v'nw a ‘-L4 ‘ vswh ”"”"\w" vh'ww-lw r' "‘4 O". KIA‘1; GK.) ~-vd. UOJ-LLDLOi‘l \n-'..U1'- \‘C k/‘I(lk‘.;-' AA'.‘ ~"‘:".,C“. C ‘J_‘\.{ .-- “2- f r. r‘ ...,\ r r ' ‘- ,— ~ - . ' '- yielueo 7.A b. (O.J,wo No-0, /) ;) oi a Lnloe cryoo.uiin ‘- A~ : ‘.. .1 ~ ' r: r- -5 I \' ‘ru ' J' ' .‘iYQI‘OCillOI‘lwe ..-.a--..,. 3.CC.1.:KSU(.. .1 1 -liza ion of tho latper fTOJ ° --‘- , .,-‘--'1 4-7. 7 ' ~--'.—~".--~ ‘. -, ~ ‘ .1. .A J».- . ' 5'. 130-! fix; .' -._L uJ..CO..C .. Jil'figkl'Q-r. a. 01130 “FOLqu “LL“..LJll/‘AS at lLFI..../- '- O lLLDQZS . 1".“97 ”—‘l V‘ " ~.~ /7|,~,,~"7!'1:. W Cr. 7-? " " . A~J --‘--‘~. C(Afic O—. 10‘. K Lg); 'A14U*A‘\). b, 1%,. j), 1., /.DO, 3. 10.34; N, 4.73; Cl, 11.93. (3\ -p O "I ~"71 ‘ ‘0 n -’\ ’ ' o 1' 1d 0 .1 .( .LOlanL. U, ‘WI‘O'If/, 1., 7./U; K-), .LOOU n '1“ n \Jl, LLQ7'C. KL"- . fi-. - .. Z . \ -|- 2-~ fl . \A. 4— ‘3‘ ‘7‘ — ‘ ‘7-Fineifli A. .1100‘11.J'rJ.-CC-€£-L£QHALO--- n€.73i.\1413fl] 3 C‘ .I ‘ "fi ’3 1‘1? 1‘4 4‘.qu V)“: r. ‘ udl--_'-'..‘<, ALJ'CL.’ 09.1-1-0; .L\ L; ’-‘.V‘ ‘ll1-~ . A Y'ffil ‘ 1..-; ~ (egorCEpzojp~fiethoxyna 1thalene. 2.3 g. (0.0122 :ole), . was .llowed to react Hi3; an o uiholar am5=uo ofJB-oip- eridinoeohyl chioride hydrochlorioe in 1L} aoueous XGOE. Icolation of the free amino and itS conversion, in the L. g g r\ .I ~/-- ' ‘- \qr ‘Qfl 1‘ . r: t\ —. "— ~ . u: . [-1. 7'°1 ".1. ."lQl", to lbs ICJCLLCCILiOI‘lMC Sula gflel-.;€'u l.l+ {13. ~ «pkg-(1A. r~ ‘ -u A .r 1' p ‘ ~ 5 ‘ '3 . ~ : '_ m~r~ ._ ‘ v f‘ . c. D.buLl§ nOle, 5h») oi Lie oesirod n.0cuCL. lulu ddtePl-l, alter CW0 recrystallizations from izworooyl alcohol, gave '30 a “Joduct with a melting point of l?h,9-155,) , / r/(} .L, .K ‘1" (J «I; :1... a.) . ‘ ~ 11er I‘ C‘s ‘.,4. L;‘ -. I r A 'V ’ - ‘P f" 17'; C40 r»_c ‘ t. f‘ . r I‘¢'-[ 'NJ I 0‘¢{ 0.1.. "\ n /\J \ . U r l’ ‘L - . .L. n.,, 4- K4 io. ,— ( . ._.O Q 2 3 1 fl} V J" l J 9).. > p U i ‘J‘C .. Mr \."'\J. ,5? / "1 b !. “flzqidooph"l —~ :1. a 1 ~ SIT .J.l C .L. ' r 6§>\\ I /\’/. (0.0315 mo; \IKII. ."i0‘" ._ I ‘-.'J p L 6.0 S. ’3 W1 ,. 1. fit \ IA \- .. . I n- v Vta’) vr‘ O k) d .ra v .19 w +1 ' $1,] LIL/16‘ n (L K . ~. , .g o . ,+ "\ N'Vyvx Lia... " ' P» . .\- . ’— "’HTQOLMJ C "*9 ; i i; .3173- r.\ -,- 4— .x L; ..‘d r\' '7 C 1". h 'V‘, “ed a as J soir of .1 n 50 m! ‘ iorioe l “1". ‘m‘ J.’ 001;... A. A." s .5 I 3- 'I ‘V ge A 13-1 .A..\.x‘ .L l Ch~ 3 1V UQCI‘ U ~s-‘ A A; law oily -30. 3’. , ~alo l O '2’} ~ ,- Ir xrhj| J ‘ a..- ‘1 insolub .1_ ‘. , "N kl LII; O? ' ‘1 nJ— v-}\4 ‘QL/Lx‘ . T" rochloride . , Li 7 h‘ cormxnrgior; .1- (3 L1 L) I .1. \r‘i lLkg a I V [“11 i 1 , noduct. .L h on ‘ .A. ”4... it) In DC 101. 1 J- 0 09:1 a]- "\ .— 4 isor" 304.1 n1 3 ll.‘¥ .11.. C r7 ( (‘7 ,.u, L, 3. LA “LIMA... n. - m f! "p mu: . f) ‘ .. (1.. 1.: -1 *- . .7 +1: . v ‘ . .. 1. ilLLTCCiJ.,,-o_.xni o i:\n_JO .uu.e (r( LGLWQi.1fl),K—C3.m‘nuo (J u. - Cl .- 4- Z O " “‘ n - ‘-r’3‘~n CW CCC ’ ”‘ ‘ w .1 ' r -.~.--~ - w‘v? “-v ~.v- -l 'T '7" “‘2 "1 "v D UK). a L\/ Clk) \,; b.L)-_ kl. n--. 1 .‘4. \ T33— .L \_. U I" C f 0.4-..- (.J“.{J.A.UJ‘ OJ. in ifirroveo ncbfioo J r fine 13et ratio- of rezone— 1..“ME JLHH- ool1er1e fiES (“'eioraci. a 5(2-belzo b *“icavlieene) rho -iine, its sooium salt aod.j§mer CptojflLE-;énzoloithieny1601ylic acid were orerarec for the first Line 1’ mo e o: tleir Dhysfca; properties were inves.ieateo£ Ofth croto~3—2-fenzoiilthienylacrylio arid to thienof3,2-E] 9 a, (D f 1 (4' i“ 0 L3 0 i (1‘ 6 6 ' 1 C) i '- O I... «D ’ 5 H- *1 C O C'.‘ {:1 k») - ‘- . 1.‘ tn '2. ~,— 4“ . . - v, I : A. lJlCDuumO-2~Cmrb0 ylic eoio SLCJ i t t it coul . - ..-..' .- ‘ 1..- .- 1'. - 1 a .,-, a PLOT, ‘re xCllZLC. of ..-O(ill€ Of." 010le8 O..lO.at lO ’1. ' 1"“ "I ‘." ‘ “ ' ‘ " “ l-‘~" ‘V -"-. - . ' " - ‘ , T 5. um [ ~i.~_,r:.ro---:y—}C-.ic.o- “11'..- Si-ll-.J_CL€.3 were Crop; reo -L I D.- vy" ¢.?-4, - J ,5 ~ra‘~ .1 - »,-\. a -: .t m. -: .01“ p.11? .Ll."ap title ELK. .01.". C. 9119-..? W’:,'S.LL<-.l hepaties were Q00-Tfllnuf. ihe o- inorOCe.20”l (Lerivatives of t «1“ - v--‘ 1~r-—r\ ¢ -. r r. , “1 P- - A j: :4- alCMHOlS Here Cu(:ecf.YrVMh1.;s‘weii es Oflu 2,L-oinitro- ‘ ‘ —‘ .-.‘ - r ‘ .. m _ .- ~ .I_ ~ I) 1" r > ~‘-' 1 _ -‘ | r‘!" ‘ DC 1 oenzo i ole_vetiae oi the a%1vwroi~-A—orooyl azyl suliiee. Seven (L(H,N-eisili"lamino) alkgl7G-naohtnyl SUlilQG ‘nvdr Chlorides wer svnthcsized for the :irst time and soge of C eir trooerties were iuvestig tea. N-dfialkvlanino) alkquz-naohthvl sulfiie 1 3 ‘~ a,\- ‘r ... ‘.‘ ‘1 r\ ';.”' f" ""'. '2‘. flycrocr lorit. . re 03-1 :gd 1c- t1- i :Q time -n .-‘ a. ' q. s.) ~,—_ ° 4— —' +- hone oi their p173 pol properties here invesCi' Cod. O ' o 1.1. ‘ ‘ r .u o 9. ~ - a . . - ‘ ¢ co . s .1. q ‘ 1'0 ~-~'~’.11r. C -1121 . C '11- w -r w 1" :1". .111 .-.( 12.1w, .2 C (‘ ’\ 4-. a: *n . ‘x‘1xfl‘; 1' 7 n-Nfir -" 4 b we ‘ ’. 4 “e A“? \) ‘ -' O L ‘r .J- - ' .o... C K‘. _.- ) k )‘V ‘ ‘1“. O.) .x l. J («\. - J kl ‘ ‘ 19.,“k/ NJ. . ‘ A A 4- -: U. I" ‘_\ 1' .- » ’« I.“ f - - - 3 ,~_ Ix -’ J _. . ‘1 q‘ ‘ -- 1‘ h , \ ‘. -. J‘- 11- r -5 1» -\ “'1 ilk) 11'" -,'O_. t OJ. fl— ' LCJN'O~I€ -..V11_’I.U_x,'rlC. ’...\_;1‘I(.\.-'\)ILL"\} p -" -'- A f‘ : " ' 1* , j, ‘ —‘ \.' O r r ' - -‘ -l .1 - R "n"‘ . n. ' m 1,13 111' {.1111 f 1 *1 Crewnmii my)” 1,0(1 £4.13... :30 C o , 7Z' ) L ‘37 4.1-6 0 J . - J— 1_’\. ”:7 ~ nr’“ r“ \/.U ' ‘ 13;}. A :Llf‘. ui.‘ \ 1 «JL ‘ ) l C) s 1 ‘ ‘ I L3 V. .... ‘1‘ L I ’. .-n.) Us. 0 , \ l I .4- 014 0 oc., C. k "‘. .LJ 0 L. IL r 7.. ‘Jo, 1950. c c—, t .4— ;Le Um '0 ‘ ' N, (‘4—I -. My , 1'." -, ~ 4C __'_'L)Q»‘L L Dr 4'1. 5; ~ l r“ N) abound“ ‘o A (‘1 Two V c -ers Inc., 1 nee Publis. SClG a, p. A. Intg 153d ‘\ 3; do“d: C) .... . In..— . A h I \fn ‘II‘ (C 3")‘30, .-1. GO) } p \ I (l 7Q (_ 1, _'__1 1“ s ‘M"Lecro 3, U). U- r,1,..-' J." A5 Ci. l LJ ._\ .1 7g F) 175131“; , .‘L 3.”. r .l . ~ In r My. 3 1 L 33.1“0 In I \ p . 'C‘) ~ 0 0L /’ D I l ( 5374 .u '. fi 9- .L‘ ,. o [..J \O O , 20 "K 'J k . I“) \J») 0 2A. ovk) . (3". "‘ I“! ('1 (‘r‘ \ . ‘vfi - (\ """ " ’C . _. ’ ‘. . l ’ \ I ‘) I ‘. I .flV L" 1 / ) l 1‘ -. ‘, 5" J ' 1,), , Ia - O A o , ...-..., _u J . , If C t ' '"L 7‘ T ‘:"r' (W 1 ,1 l, ’7’ r ( } I I, I o ‘l v 0 I. C UO‘ L . ,. 1. U4- , U I A) ’ ‘ x \4 \ y./ . ' . as. > ‘“ «A. ."“~ » - , £2 '3'” . J. C. L -.k '5 v.1(l 1. UkuLlnng [I , d . kl H4 . k)“; ..l. , rd" , ;-jl— /‘ 3/ . - - J . - v, . [1 o c " { ‘ 1" I. - x ' ~ «4 ~ -‘ t‘ .‘--I 1 .‘ I :3 . 1-. \I. n; ‘\ J__S , 4‘ LL4D--&J I k’UL " [AA—J- ., l/Dl. " ' “‘3 ‘~ [1 o a 1 . ’. .1 ' _- ‘r‘ . ‘ ~¢ m r r'~ ' fl ’ r" ‘ ‘ - " " o I . A-- .L.‘ , J‘.. L,. ALLJL. _L,’ A...L\z ...L,t . ‘ U€ ‘ -1—-V., lei/.... ) tnfivnv‘n >“ x ”1,. ~ »:VA~°~n (”~fi U ‘ lcr’ sL. ’-. 'CxJ-\/."_L$L, 1.. 5/. ~iiK/b;...' , 4. i£5;1(.>(. A A‘IJC’AtO nLV. ’ /Db. ' “' -' d " -; «a 1': c « - .w . U. AI. . s..«L- ..LLJ. 9 it . I\‘ ...KLLJ’ ..J. \J. .AJ..L....-L_.- , kt. -.J..\n(.t.....3 \1 1‘1 ‘__- §—. - /-' 1 IN; fi ’ -'I \ Y‘r. ,, ' ' -.J," " $5 I I. ’ K" \ "fl (IQ *“ . ‘.\g . Aa‘ . ‘ .. \.' .3‘ ’ U. VA Ii: . '- le . ) . -..V) .1_// J) . f r C K} ) C‘) P 5 b 5‘ 5. C) r O P‘J lI . u C4 0 D I‘r...’ O C) a O O ( J H u \-) (\D b > \0 . ..th‘1 f 4 (“"5" (fix ,‘7 ‘ 'h\ l'. ‘ "X 7 (‘5!) CI‘ ,"1 2-. ... ‘ l.“(-.1.;’.l‘.\'a C.X.‘~-, 1L. ..J. v.4.lnb, (J. J-n-g. #LC’A:I. , i, ,4 ‘_‘ l - - > ,2 C ... 1‘ ,. 614531 ' "11%): 11:... 1,7 , J'L'AJV (_(/2) ) . *7 '1 “"h v-f~—- T‘ -. f“ _' 16/ \ ‘ "‘ t ' ' . i) J‘CLLI._;.AC‘.;‘L‘1, D84 . , _r‘j.,, \I‘rf7 (Ar-LO]. ClleoL. J-USt/r‘. , L ——- 5. u» .0 .‘_ .f ‘ 1.. r. \ fl '\ .' - ‘ r\ _' ’ ‘ V‘ fl. . o r . “Lgilsuh;qs Landoucn no: 033%. -eu Lb.ule,’ Vol. V1, V 3 1'51; 9‘ t' )1: Julius ES “5 1’1 :3 r3 ,1" .«_£e:'_'-i21 GC :11: '3 '-.’ 1941 k 3 i _ K.) , , , , 3:) . \J :5; . \ (7' m .‘ t. ,‘ 'T " ". M 1m' . - “a .- ~ J. u. -aroelh :nq J. n. filnu3n1m&, J. hm. the“. uvv., loc., 1 ‘V .. Jul 4» V‘fl . A-.. I . ....;-OI'1, fl' 1. H n J}. k 0 1“] r‘w Ar. 4—- 7(3‘ q ‘_,” 1"" 0...... and "\ III, ChLLo '01 V H fi‘l fax "' ”1"?01117. '\ . q-. 5 4.4.x; UV. '--.‘MI‘ ~ x l \l‘ I 4--. U-. Y. .11. :‘Tar‘. " K) \_' __ I on Of. ,-\ .-\_l‘ qc\ J- 2; l c . 'k J ...J \ (N I ‘_‘ b C _. CFZ'U. -"1 A "x. L K) AL A 1770113 , uOE“. 'rnrr'" r‘ '5 k)(~‘ ~~c ’\ . \1 n1 .1 A’. VF ‘ 1111 . 0 ~. war; ‘5 .. g-.- ‘- 16‘, tor r‘ L oh1 712, (‘a L' g} D. A. MICHIGAN STATE UNIVERSITY LIBRA I II II lllHllHl 3 1293 030I12644 RIES