f».‘r.“.‘.‘...r.m—u.nnou~~an .. u, n. THE SYNTHESIS AND STUDY OF SOME WIAWHTHENETHIOLS AND tut-(N, N‘DIALKYLAMENQ) ALKYL THIANAPHTHYL .SUU‘BDES 11nd. hr the ma m 0. mm sun mm mm a. new ' 13956 THESIS Xi , 7 , This is to certify that the . thesis entitled "The Synthesis and Study of Some Thianaphthenei and fl-(N,N-Dialkylamino) Alkyl Thianaphthyl Sulfieds. ‘ ' presented by Charles E. Heyd has been accepted towards fulfillment of the requirements for PhoD. degree in Chemistgy Date Oct. 15, 1956 0—169 LIBRARY Michigan Sun University PLACE IN RETURN BOX to remove this checkout from your record. TO AVOID FINES return on or before date due. MAY BE RECALLED with earlier due date if requested. DATE DUE DATE DUE DATE DUE 6/01 cJCIRCIDateDuepss-sz THE SYNTHESIS AND STUDY OF SOME THIANAPHTHENETHIOLS AND hF(N,N-DIALKYLAMINO) ALKYL THIANAPHTHYL SULFIDES By V s”: t; 3‘ Charles E. Heyd A THESIS Submitted to the School of Graduate Studies of Michigan State University of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry 1956 ACfHONLEDGMSNT The author would like to express his sincere appreciation to Dr. Robert D. Schuetz for his guidance and friendship throughout the course of this work. He is also indebted to his parents for their financial assistance. _v_.V..V._V._~I_v_V.v_~I.v. I\ I\I\I\I\I\I\I\I\I\ ii VITA Charles E. Heyd candidate for the degree of Doctor of Philosophy Dissertation: The Synthesis and Study of Some Thianaphthenethiols and Q¥(N,N—Dialkylamino) Alkyl Thianaphthyl Sulfides Outline of Studies Major Subject: Organic Chemistry Minor Subjects: Physical and Inorganic Chemistry Biographical Items Born, March 3, 1928, Detroit, Michigan Undergraduate Studies, B. S., University of Detroit, 1950 Graduate Studies, M. S., University of Detroit, 1952 Michigan State University, 1952-1956 Experience: Graduate Assistantships, University of Detroit, 1950-1952 Michigan State University, 1952—1956 Professional Affiliations: American Chemical Society The Society of Sigma Xi iv THE SYNTHESIS AND STUDY OF SOME THIANAPHTHERETHIOLS AND 0-(N,N-DIALKYLAI£INO) ALKXL THIAI‘JAPHTHE SULFIDSS By Charles E. Heyd AN ABSTRACT Submitted to the School of Graduate Studies of Michigan State University of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Chemistry Year 1956 Approved This study deals with an investigation of the heretofore unknown thianaphthenethiols, and the synthesis from them of thianaphthyl alkyl sulfides having a tertiary amino group on the terminal carbon of the alkyl chain. This study was undertaken for the purpose of extending the work previously done in the field of synthetic local anesthetics con— taining the thio ether linkage (1,2,3). These compounds can be repre- sented by the general formula, The thianaph henethiols, 2-thianaphthenethiol, 3-methyl-2-thia- naphthenethiol, 3,5-dimethylthianaphthenethiol, and 3,7-cinethy thia— naphthenethiol, were prepared by the metalation of the appropriate thianaphthene derivative with n-butyl lithium, and subsequent reaction with powdered sulfur. The general reaction scieme is illustrated for the preparation of 2-thianaphthenethiol, etiter 3_ 1,1 V + n-C4H9Li S S H «H.251... The mercaptan 3-thianaphthenethiol was synthesized by employing a Griqnard reaction starting with 3—iodothianaphthene, I 1%? l l Iinl V ' l I ether 8 U) H a o ; Shel 19—;41..._ The preparation of thiols by the reduction of sulfonyl chlorides with litiium aluminum hydride was found inapplicable to thianaphthene as a synthetic approach due to the sensitivity of the latter towards chlorosulfonic acid. The preparation of the tertiary aminoalkyl thianaphthyl sulfides can be represented by the general equation, 3 .. .' ‘> ‘ I. . SH i S-(CH2)n-N\ vi The tertiary amino alkyl chloride hydrochlorides, (g-dinetnylanino- ethyl, 9 -diethylaminoethyl, Y-di;uethylarriino-n—propyl, 0k -methyl- 9-Cli- methylaminoethyl, 9 -m,orpholinoethyl, Y -i:iorpholino-n-propyl, Q -piperdino- ethyl, Y-piperdino-n-propyl, Q-tl'iiomorpholinoethyl, and Y—thio— morpholino-n-propyl chloride hydrochlorides, were used in the present investigation. 11 """ ‘TW {‘1‘ "1'~'1r1 'L; Dr tun;li-_3 flirt» “ r. 1 ILLEGJLCPIUN...ooooooooooooooooooooooooooooooococooQOOooooooo hlk‘le)é~\rI‘3—.ALOOOOOOOOO.00....0.0.00....00.000.000.000...00...... Local An J4SU‘letj—CSooooooo0.0000000000000000000000oooooooooo illiallat)}lbli(3n000.0.00...OOOOOOOOOOOOOOOOO.OOOOOOOOIOOOOOOIO hleDuldnepHLd3n38.......o................................ AlkylthianaphtNenes....................................... DISCUSSIQIIOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOCOOOOOOOOOOOOOOOOIOO. ‘ 5.1).;ALL_L.ILE:i—lju-JO0.0.0.000...OO.0.0.0.0....OOOOOOOOOOOOOOOOOOOOOO Preparation of Halothianaphthenes......................... Preparation of Acetonyl Phenyl Sulfides................... Preparation of Alkylthianaphthenes........................ Preparation of Thianaphtnenetniols........................ Reduction of 2 ,2‘-Thianopl¢thyl bisuliide.................. Reduction of 2-Le unyltnianaoxt enemonosulionyl Ciloride .. Reduction oi W iananliuen,monosulionfl Chloride........... Reaction oi Tni anaontnene with Uhlorosulfonic Acid........ Reaction of 2 gotnyltiian _-htnene with Chlorosulfonic Acid Reaction of j-notivitiianaimtn3n“ with Chlorosulfonic Acid Preparation oi€J—(J,m-JiaiL/lamiro) A.ll:yl Cnlorid es Iiyo ro— chlorides.............................................. Preparation oi(D- (N,N-gialkylamino) Alkyl Thianap ethyl Suliide Ha drocnlorides................................. SUEZ“ M:Y...00.......OOOOOOOOOOOOOOOO.OOOOOOOOOOOOOOOOOOOOOOOOO BIBLIOGHAPElfo00000000000000.0000.coo.coo-0.000000000000000... viii }__J [\3 \O \1 \7‘1 [‘0 F‘ R) L O\ \J‘ KL) K] H C23 6* \I’i. \H, K] }-’ \O O\ I O'\ O\ \JT “J”; \\3_". \[1 \(D K O\ H O x C: ) I \s. R) \ , , ~ , ‘\ , ‘ 6 3 i a 1 - w ~ , , ’1 \ . .. m, , .,. , .. \ r w h fi < - -. ~ " n - . . x — 1 v , ‘ . Q — . , . n g - < ‘ a 1 , - .‘ . n ' n x - , , . _ . i .‘ . ,. - n r a m TABLE I II III LIST OF TABLES daney Nickel deduction of Thianaphtbene Compounds....... j-T}1ianap}lt}lenet}lj-OlsOOO...OOOOOOOCOOOOOOOOOOOOO00...... 2-‘P11iamphthel’le-‘b‘xlj—OlsO0......0.00.00...0.0.0....0.0.0... IV (J-(Dialkylamino) A.kyl-2-Thianaphtnyl Sulfide Ii:)rCLrOC:1]—0rides..00.0.0000...OOIOOOOOCOOOOOOOOOO00.... V (J-(Dialkylamino) Alkyl—3-hethyl-2-Thianaphtnyl Sulfide iiy-drOCEIlOI‘j—desoOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOOO ‘VI (d-(Dialkylamino) Alkyl—B-Thianaphthyl Sulfide Iiydljoc‘illoriaeSOOOO0.0000000000000000000...0.000000... ix pi \A‘ K») J- FIG"3 I II III IV VI VII VIII LIST OF IN ZiAI 3D FIGUtSS 3‘“ Tlllananlb’l IIIJUiliOloooo009009000000-oooooooooooon 3-(2,h-Dinitrophenyl) Thianaphtnyl Sulfide........ ~notnjltnianapntiyl-g (2,4-Dinitr0pncnrl) Suliide 2—T}‘lianap11ti-ilene-tliiOl.. ........ .... ... . ... 0.... O . .L a 3-HetW1yl —2- Hflianapnt ' enetnio l................... 1 3(2, u-Dinitrophenyl) Thianapnt i ‘fivv U “"11 ei"t1y13- ISOpl‘Ople BDZBDG..........o.....o.o. l Sulfide...... 2-Ietnvlt ianaohtnyl-B- -(2,h-Dinitrophen3;l) Suliide. ‘r J. 4". P a 2-18 V rb‘ 7* . I ;,a ,~‘_ -£'v-Q".;-—:— -q—-—-—~‘- r ‘3; ~w' “v— INTRODUCTION Thianaphthene was first prepared by Gattermann and Lockhart in the year 1893 (h). Since that time many investigations dealing with thia- naphthene have been recorded in the chemical literature. However, there are numerous problems dealing with this material yet to be solved. Host of the studies in thianaphthene chemistry have been on the hydroxy- thianaphthenes and quinones as these materials are essential intermediates in the synthesis of the commercially important thioindigo dyes. Other derivatives of thianaphthene have not received nearly the attention given the hydroxy compounds, and as a consequence many phases of thia- naphthene chemistry are still in need of study. One such phase that has received only the most limited amount of work is that of the sulfur derivatives of thianaphthene. No sulfides, sulfoxides, sulfones or thiols have been reported, and only a few random cases of sulionation have been published in the chemical literature. The main objectives of this study were to investigate possible methods of obtaining thianapnthenethiols, and to then employ the thiols in the synthesis of compounds which should have potential use as local anesthetics. HISTORICAL There are two general groups of drugs used for the production of local anesthesia. To the first group belong such substances as ethyl chloride which causes anesthesia by refrigeration. The second group of drugs comprises substances which produce a selective paralvsis of sensory nerves. The second group may be divided into two classes. Into the first fall substances almost insoluble in water and which are therefore used as dusting powders or in the form of ointments. An example of this class is ethyl p-amino benzoate or benzocaine. The members of t he second class are soluble in water. The best known example of this class is grocaine hydrochloride or 2-diethylamino ethyl p-amino benzoate hydrochloride. The use of local anesthetics in medicine dates back to the last two decades of the nineteenth century when cocaine was introduced by Karl Koller (S) as an anesthetic for the eye. However, the fact that a large number of people show a dangerously high degree of addiction to cocaine has been one of the main reasons for seeking substitutes for cocaine as a local anesthetic. The science of synthetic local anesthetics dates from the discovery " I of Lihhorn (6) that esters of p-aminobenzoic acid produces surface anesthesia. Since that time numerous investigations have been directed toward the preparation of compounds having the general features indi- cated in the formula, / A-M-( c )n-N\ Here A represents an aryl group, and M is a heteroatom or heterogroup. These features are considered to be reSponsible for the local anesthetic preperties of cocaine. Until recent years, most of the compounds prepared showing activity as local anesthetics were related to cocaine or novocaine. Studies made in the past few years have shown that compounds possessing widely different structures also possess anesthetic activity. These include mine alcohols, sterols, and ethers containing a tertiary amino group. More recently, Schuetz (1,2,7) and Campaigne (8) have investigated a a tertiary L) the activity of various organic sulfur compounds possessin amino group. A group of phenyl sulfides was prepared having the follow- ing structure (I), C6H5-S-(3H2)n-R-H3l where n varied from two to six and R was equivalent to piperdino, ; U) .54 9‘ Li) "S (’ morpholino, diethylamino and dimethylamino. All of these compounr found to possess anesthetic activity in the range of procaine. Due to the chenical similarity of benzene and thiophene, Campaigne and LeSuer (8) prepared a series of esters having the following structure, COQ“(CH2)H“R0H01 where n varied from two to three and R was equivalent to morpholino, dimethylamino, diethylamino, di-n—prOpylamino, and di-n—butylawino. Only the -di-n-butvl—h-,ropyl derivative showed any anesthetic activit‘. u t . , L l],— The toxicity of these compounds is similar to the p-aminobenzoates. Houff and Schuetz (7) studied the properties of some derivatives of 2—thenoic acid. where n was either two or three and R was piperdino or morpholino. These compounds were comparable to procaine in wheal tests in guinea pies and possessed low toxicity. Later studies by these same workers were carried out on derivatives of 3-thiophenethiol (2), S-(CH2)n—loHCl Here, n varied in these compounds from two to five and R was piperdino or morpholino. Pharmacological tests indicated a high activity. An interesting group of compounds was prepared by Burrows and Reid (9) having the tertiary amine group in the form of a thiomorpholino ring, cog-(CH2)n-N‘ >s.Hc with n equal to two or three. The n—propyl derivative was found to be about as effective as procaine, but less toxic. V"; Burtner and Lehmann (10) prepared a derivative of dibenaothiophene of the following structure. by _cw or r’c * ) .wc O _ QCZ U..2"u112“\u2[i:} 2 .LLJ... It showed a weak anesthetic action in the rabbit cornea test. Since both the benzene and thiophene nuclei have been incorporated separately in numerous compounds studied over recent years as local anesthetics, it was thought that the preparation of derivatives contain- ing these features combined in a single molecule, as is found in thia- naphthene, would be of interest. Thianaphthene is the name currently used for the ring system (I) I \. by Che ical Abstragts. The alternate nu bering system (II) is found occasionally in early literature. Prior to 1937, the nafle h 3 5 3 u 2 6W2 90 1 7 l 6 I II benzothiophene, which was first used by the original German workers, was employed by ghenical;Abstracts, and the British Abstracts still use this form. Detailed descriptions of the Chemistry of thianapntxx found in books by SteinkOpf (ll), and Fukushima (12). Recently, an excellent coverage by Hartough and heisel (13) has been published, 1 which contains the majority of references through the first half of l9i2. Juan-i, w.- - _..v—_ . P .u The first derivative of thianaphthene, h-hydroxythianaphthcne, was prepared in 1886 by Biedermann (1h) from thiophene—Z—aldehyde and sodium succinate. This reaction is similar to that used to prepare °(-naphthol from benzaldehyde. O "a 0-D? _ (VII, 1 O Acetic -2 \ _.-~ I + :C- Anhydrioe CH2 H H020 “”-01 H O Thianaphthene was obtained synthetically before it was isolated from natural sources. Gattermann and Lockhart (b) first prepared it by heating at its reflux temperature an alkaline alcoholic solution of o-rnercapto- Q -chlorostyrene . ---—----> \ It was not until 1902 that Boes (15) was able to isolate thia- naphthene from coal tar. He separated it from the naphthalene fraction by means of its picrate derivative. Thilnaphthene can be produced by the dehydrogenation of ethyl— benzene (16) and subsequent reaction of the styrene with hydrogen sulfide, or from styrene and hydrogen sulfide (17). Friedlander (18) prepared thianaphthene by the oxidation of o-mercaptocinnamic acid with potassium ferricyanide. CHO CH=CHC U ca=cacogi: , ————~-e> [ moz {H2 I—“U U [:jljl‘T02 CL— “cog“ (“O-*— h, Sh synthesis of thianaphthene widely used is the reduction of zinc dust (19). 3— nydioxytnianapnt‘ene by means oi cogs --—~e> . SCcho «~— In“ ‘ cogs There has been no systematic study of the halogenation of thia— naphthcno. Rorm ppa (20 c) was the first to chlor inate t1ianapntne He obtained a dichlorothianaphthene, presumably the 2,3-derivative. Schle Sing r(2l) ootained 3-—chlorothia11aphfi ne in low yield byt 1e hlorination of thianaphthene in carbon tetracl iloride as a sol ent. The perchloro derivative of thianaphthene, 2,3,h,5,6,7-hexachlorothia- naphthene, was prepared by Barger (22) as indicated in the equation, C1 C1 C1 SOC12,SOBC12 CHCHBBI‘ _O ’ C1 Cl Br 270 Cl Bromination of th ianaphthene yields a variety of products depending ‘ upon the reaction conditions. Mono, di, tri, and tetrabromo oerivativcs L'J .‘Jfir.’ are known. A monobromo derivative, 3-bromothianaphthene was prepared by treating thianaphthene with bromine in chloroform as a solvent at a temperature of 3000. (20). A 2-bromothianaphthene results irom the interaction of 2-thianaphthyllithium with bromine in ether solution (23). Only three iodo derivatives are reported in the chemical literature. The 2-1000tnianathnsne results from the treatment, in an ether solution, 1-1-1 of 2-thianapntnyllithium with iodine (2h). The 3-iodo-derivative results from the tread tm ent of thianaphthene with iodine and mercuric oxide (2n). 2,3-diiodothianaphthene has been prepared by treating 2,3-thianaphthenedimercurichloride with iodine in carbon tetrachloride ). Lietalation of thian phth ene with sodamide in liquid ammonia (26), (2 \JT or with n-butyl lithium in ether (27) occurs in the two position. That metalation occurs in the two position has been verified by the fact that the methyltnianapnthne obtained from the reaction of thianaphthyl- lithium with methyl p-toluenesulfonate, and tile 2—m3t thylthianaphthene prepared by LC th and Kiss (28) by the following unequivocal synthesis are identical. 0 II + CH CIECOBH -——«> 3;ch ‘ SH Br \S-Cl/‘i-‘CI I3 CH3 Zn-hg HOAC ' * «~1— .Cj s CH3 ' . s CH, The alkylthianaphthenes are formed by either a ring closure re- action or the dire ct alkylation of tho thianaphthene nu cle The compound 2-methylthianaphthcne is obtained from the reaction of 2-thia- naphthenyllithium with methyl p-toluenesulfonate (23). It has also been prepared in low yield by the vapor phase dehydrogenation of o-n- propylbenze ethiol (29). Tie alkyl derivative, 3—methylthianap.thene, was obtained by werner (30) by the dehydration of phenyla icetonyl sul:ide. Oils fl% POO“ _€> ‘ l s -+ H20 S-CVB c} The alkylthianaphthe e, g-t- -butylthiana phthene, recently reported by Corson (31), was prepared by the reaction of thianaphthene with Hare; C(CH3)3 + CH3e=CH2 Is 0 The structure of this derivative of thianaphthene was established by isooutylene, esulfurization with ianey nicte The use of Raney nickel as a desulfurizing agent has found popular use in the structure proof of several thianaphthene compounds. Table I lists the compounds that have been subjected to such a reaction. A very limited amount of work has been done on tile sulfur deriva- tives of thianaphthene. No thiols, sulfides, sulfoxides, or sulfones have as yet been recorded in the chemical literature. Komppa (20) treated thianaphthene with 5% sulfuric acid and obtained a lO TMLEI J L-O {-4 RAl‘tfl'Y IICKEIL REDUCTION OF TIILAJQAPHTEEEE OI-EOUI‘EDS Compound Reduced Products Reference Thianaphthene Ethylbenzene 32 3—Hydroxythianaphthene Ethylbenzene 32 2—Thianaphthene caTbOXVliC acid CCHECHQCHQCOEH 33 3—Thianaphthene carboxylic acid CSHECH(CH 3-t-Butylthianaphthene C€H50H(CHB 0(01'3)3 31 O h-Hydroxythianaphthen— o-Bthylphenol, 34 o-Ethylthiophenol _.__‘ ——-—-—~ #7.... ‘0 "EV-‘gflji'r _ monothianaphthenesulfonic acid, isolated as its sodium salt. He also reported that some disulfonic acid wa formed during the reaction. However, he reported no structure study on any of these compounds. Only one thianaphthene derivative containing a sulfonic acid group in the benzene ring has been reported. Fieser (35) prepared it by the following seouence of reactions 1) .L ’ NO _ NON HO 12 DISCUSSION The preparation of 3-thianaphthenethiol was accomplished by the reaction of 3-thianaphthenemagnesium iodide with powdered sulfur. C H // I I + I2 —i——>Hg06 |\/“ l I? «2% SH SMgI */ . a Go , s The iodo derivative was used in the Grignard reaction in preference MgI to the 3-bromothianaphthene since it is more reactive towards magnesium. However, with both 3-iodo and 3-bromothianaphthene an appreciable amount of unreacted magnesium was always present at the conclusion of the Grignard reaction. The use of 3-bromothianaphthene in the Grignard reaction requires the presence of a simple alkyl halide to promote the reaction. The yield of 3—thianaphthenethiol was not particularly good, in any of the several experiments carried out for its preparation. A yield of thirty percent was never attained; the maximum being about twenty-six percent. The mercaptan, 3—thianaphthenethiol is a yellow colored liquid possessing a characteristic mercaptan like odor. The elemental analyses of the liquid thiols prepared in this study were carried out on their reSpective 2,h-dinitrophenyl sulfides since the thiols were observed to be quite unstable. It was found that the H KA) base soluble thiol obtained immediately following its vacuum distilla- tion soon exhibited some degree of insolubility in alkaline solution, even when kept in a refrigerator in a tightly closed container. For this reason, the infrared spectra of the thiols were recorded on a sample obtained immediately after distillation and which had been ‘ checked for complete solubility in an alkaline solution. The infrared absorption spectrum of 3-thianaphthenethiol is shown in Figure I. InSpection of the curve reveals the sulfhydryl band near h u; the strong, selective band for thianaphthene at 9.5 p; and the wide band at 13 u indicative of monosubstitution in the three position. A band in the 7.95 p - 8.15 p region usually identifies sulfur in a five membered ring. The strong band at 3.25‘u is characteristic of the carbon 1ydrogen stretching vibration. Figure II shows the infrared absorption Spectrum of 3-(2,h-dinitrophenyl) thianaphthylsulfide in carbon disulfide. The strong band at 7.5 p is characteristic of the aromatic nitro group. 2—Wethyl-3-thianaphthenethiol was prepared from the previously unknown 2—methyl-3-iodothianaphthene by the following sequence of _reactions. . _|I MC" Lg]: I use... boiler II, . / 1-3 CHIS S 8 SH Sth g ago CH:3 e113 lb V. n. N. O. H mwnmflm 40.1» uzmxhzaS‘d—Ih‘n a O h @ mzocuzl z. o theta; u><3 v n O N O C NOISSIHSNVUL 3 O 0 00 O. . / v. n. N. 3.3.5 31.2.2215..izuzaoctzsedh O. h atop-0.8 z. zhozu4u>i v n flu O O N O O NOISSINSNVUL} 00 The thiol was characterized by the preparation of its 2,h—dinitrophenyl- ’1 sulfide derivative. The inirared spectrum of this derivative in carbon disulfide is shown in Figure 111. The necessary intermediate, 2-methy1-3—iodothianaphthene, was prepared by the direct iodination of 2-methylthianaphthene. The position of halogenation was established by the carbonation of the Grignard reagent 2-methylthianaphthene-3—magnesium iodide to the known 2-methyl- 3-thianaphthene carboxylic acid (36). The heretofore unknown 3-thianaphthcnethiols prepared in the course of this investigation and their 2,h-dinitrophenyl sulfide derivatives are reported in Table II. The previously unknown 2-thianaphthenethiols prepared during this study and their 2,h-dinitrophenyl sulfide derivatives are listed in Table III. All of these hetrocyclic mercaptans were prepared from the appropriate thianaphthenes by reans of a metalation reaction. The several reaction steps used in the synthesis of these compounds can be presented as follows, - . ether + n-C h 11 --——~+> . 49 L1 H20 A SH The metalation of thianaphthene with n-butyl lithium has been described by Shirley (23). The 2—thianaphthenethiol is a white crystalline, low . ."-_".": mega, a.-.__ . n( l I n. N. HHH my 0 3.11 n.\(. F 1‘ v 0...». 3.5:» arzuxaofizaiurn...»32.22525»sz O. h 2.93:. z. :Szud>§ o v n u, 3 a uoussmsum: O O F '9— I K. 'J .HHH «mflxoxm «.qu .comeuopoflz he mammamm¢ Hocmzpomnm ”COHpeNflHHmpmmpoem pom mpcebaom l. l: !. .... m m _- aca { a a m e soaemao amnemo see 0 3. I J J . \m tea Ada m eaa-maa eNmNZassevHo mmeeeo m L . Afloaee Ameaeaemaaeoed .2: .o Ameaaaem empmHSOpr pamaw capac4alan . .c :4 a. . I , _ . . a .p l NV Afloaee -Haemeaoweaean-a.mv A o4e . eraHSmrhcezgoasrcaann. mama w Coop . a. .. . . . .L . H «.Bv w 4 .L _ NV . a me p . om so a r a m massage a em manHzewmmmammemaHeeum HH m mnH .HHH .maeomm ..pea .eomBIOhoae an mamaaeea ecmxoflo mpdfiflenn «Hocmrpemlm “Cowpmwflaaepmhpomp pom mume>aom + o \ \o J}. \ l. o x \\ \ \.\ .. . x a. U H. H .3 . ma... _; m my mm «w m am mu .m mausma mm una-mma hmmmeacmai no «mo :0 0 ago e we . -.-\ .... ix. , - :+ -. , 1 .aa.. a. 4 m. m. cu m me at mm V 0a nu ma mamtmaa gm L;ruaga emmmzaec "Lao Nmo ro.o : am re 0 F4 O{\ O \O \ .1 :.II .. . ‘v 1‘ ufl a 2H m... a 1 «u I mad no N ;c at Ho m me Ht 0; arm-mam m mHH10HH maccaaoo :. m «m roe : e :o \O L O .\. 13.. O \. ..\ I \ O .4 I. t 7‘ 1! m H .1 ch 4 . at m a. as a: N am at an oem-aea A a av msl.a; mmmozvo me 0 mm e o e m e e o e o Afloaeev Ameaeaemaaemea Ameaeaem cease eoemasano eamae -oteaeaa-e.mv a: so Heemeaoseaea -e.mv Afloaeev AdeflaHSmHMQecmoapflcflQusnmV pumoaem .ooa.m.m Aaoflzev wadeaom ..m .n m mammflmcd .m.m _.fi a» mHOHmEfiwflmHmmdmemelm HHH mamae 2O melting solid, whereas, the other 2—thiol compounds are all liquids at (*1 room temperature. They are all sensitive to air oxidation. The infrared spectrum of 2-thianaphthenetaiol in carbon tetra— chloride is shown in Figure V. The position of metalation of 3-methy1thianaphthene was established ’1 as the two position by carbonating a small quantity 01 the metalation reaction mixture with solid carbon dioxide. The melting point of the acid obtained following hydrolysis of the product was the same as that reported for 3-methyl-2—thianaphthene carboxylic adid by Gaertner (37). The infrared spectrum of 3-methyl-2—thianaphthenethiol in carbon tetrachloride is shown in Figure V. The position of metalation of the dialkylthianaphthenes is presumed to also occur as is usual in the two position. The 3-alkylthianaphthenes used for the preparation of the 3-alxyl 2-thianaphthenethiols were prepared by a ring closure reaction using phosphorous pentoxide with the appropriate acetonyl phenyl sulfides. The method of'herner (30) for the synthesis of alkylthianaphthenes was successfully extended to acetonyl-p-tolyl and acetonyl-o-tolyl sulfides. The extension of this synthetic method to p-methoxy and o-methoxy phenyl acetonyl sulfides was not successful. The ring closure reaction was always accompanied by extreme darkening of the reaction mixture and apparent decomposition. The thianaphthene derivative obtained by the ring closure of acetonyl-o-tolyl sulfide was a previously unknown dialkylthianaphthene. B. 830.2 40 _Shlluxhxt¢8¢_:hld = O. O I m2 0&2! z. IP02 u4m><~> h 0 D Q n on 0' 6. do. NOISSIWSNVULX e Edam .— 0 .8h .8. 8h:t¢8¢.8hl~l4> Skull. m20¢0_8 z. IP92NJN><3 h C NOISSINSNV8L% [”0 be The structure for this compound was established by its desulfurization with Raney nickel. I I NL-e- Uha CH-OH CH3 C113 The expected desulfurization product, m—cymene, was identified by its boiling point, refractive index, and a comparison of its infrared spectrum with that of an authentic sample, of m—cymene kindly supplied by the National Bureau of Standards. The curves shown in Figure VI shows the infrared absorption Spectrum of the compound obtained by desulfurization and also the curve of the authentic m-cymene. In addition to the Grignard and metalation synthesis of thia- naphthenethiols, another route to their preparation was desirable since the former two methods would be limited in their usefulness to obtain derivatives of the thianaphthenethiols in cases where a reactive group was already present in the thianaphthene nucleus prior to the intro- duction of the mercapto group. A well known synthesis of thiols is by the reduction of the corresponding sulfonyl chloride. In the aromatic series, the sulfonyl chlorides are readily obtained by treating the aromatic compound with chlorosulfonic acid. This sequence of reaction for the introduction of the mercapto group into heterocyclic compounds has been recently applied to thiOphene derivatives by R. J. Fawcett (Ph. D. Thesis, Michigan State University). The initial studies on the chlorosulfonation of thianaphthene com- pounds were carried out on the parent compound. It became evident 3 TRANSMISSION S YRANSIISSION I00 00 SO 40 20 I00 SO 0 O b O N O 2 3 VIAVE LENGTH IN NICRONS 4 I 9 IO II I2 IS I4 I-NETNYL-S-ISOPROPYLOENZENE W 2 3 WAVELENGTH IN MICRONS 4 7 S 9 IO II I2 I3 l4 I-METHYL-S-ISOPROPYLOENZENE NATIONAL BUREAU OF STANDARDS SAMPLE l‘ i {fare W; ('3' as. 23 after a fewe ::periments that this reaction then applied to thianaph- thene was quite sensitive to both temperature and the quantities of reagents. The chlorosulionation reaction mixture usually became very dark colored after a small amount of thianaphthene had been added to it. It was apparent after removing the solvent layer that very little thianaphthene we .5 being converted directly to its sulfonyl chloride derivative. A reasonable possibility seemed to be that a thianaphthene sulfonic acid was actually the product being formed and of course would be expected to be found in the water la3er. The aqueous layer was neutralized first with barium carbonate, filtered, and the filtrate treated with sodium carbonate, filtered to remove th e mr we _pitated barium carbonate, and evaporated to dryness. The resulting solid residue was treated with phosphorous pentachloride with the intention of converting the sodium suL”onate to the sulfon3 l chloride. This procedure yielded a dark oil which was very diiiicult to distill even at very low pressures due to its rapid thermal decomposition. ”QCUPblOD of the crude oil with lithium aluminum hydride was not successful because of excessive fuming and sparking during the course of the re- action which necessitated stoppin U1e experiment. However, during one of the dis tillations on the crud de oil, a small amount of distillate was obtained. This material analyzed correctly for a monosulfonyl chloride, formed a sulfonamide and has an infrared spectrum showing two strong bands at 8.3u.p.and 7. 2S‘y.. Szhrieber (3d) not cthat benzene sulfonyl chloride exhibited two strong bands at 8.h2‘n and 7.h6 p. However, very little Spectral data has been reported on the organic sulfonyl chlorides as a class of compounds. A small sample of this distilled sulfonyl chloride was reduced with lithium aluminum hydride and the resulting thiol characterized as its 2,h-dinitrophenyl sulfide. The inirared spectrum of this derivative in carbon disulfide is shown in Figure VII. The mixed melting points of this derivative with the 2,h—dinitrophenyl sulfide derivatives prepared from known samples oi‘2- and 3—thianaphthenethiol showed no depression with the 3—substituted derivative and an appreciable depression with the 2-substituted derivative. These results indicate that the sulfon- atien of thianaphthene occurred as expected in the three position of the thianaphthene nucleus. This conclusion is further supported by a comparison of the infrared curves (Figures II and VII) of the 2,h-di- nitrophenyl sulfide derivative of 3-thianaphthenethiol, the latter material having been prepared by an independent synthesis already discussed. These curves are seen to be identical. Several chlorosulfonations of thianaphthene were carried out at lower temperatures in an attempt to reduce the amount of decomposition occurring during the reaction. An experiment on the chlorosulfonation of thianaphthene carried out at a temperature of -37OC. resulted in no reaction and recovery of the starting material. Another such reaction conducted at a temperature of -lSoC. yielded a product having no halogen present, but which gave an elemental analysis close to that of dithia— naphthyl sulfone, and the product had an infrared curve in chloroform with maxima at 7.55, 8.70, and 8.85 y. Schrieber (38) proposed the ranges 8.62-8.92 and 7.h2-7.69 p, for the characterization of normal sulfones. HS 9:3 mo Edam J>Ih1¢¢2$1h 3>zuza0¢tzauvdvh O. h o t m20¢0.8 2. Ihezwau>(3 n O O Q N NOISS'NSNWJ. S O 0 00 \ 28 The chlorosulfonation of 3-methylthianaphthene with an excess of chlorosulfonic acid gave a product which had the correct elemental analysis for a disuljonyl chloride derivative of 3-methylthianaphthene. The infrared spectrum of this compound in carbon tetrachloride shows strong peaks at 7.20 and 8.50 p, It also formed an amide having the correct elemental analysis for a disulfonamide of 3-methylthianaphthene. The position of one of the sulfonyl chloride groups in the this— naphthene ring is very probably in the two position. The location of the second group in the benzene portion of the thianaphthene nucleus was not determined. The chlorcsulfonation of 2—methylthianaphthene yielded a variety of products depending upon the ex erimental conditions of the reaction. In an ekperiment carried out by adding the 2-methylthianaphthene to the chlorosulfonic acid yielded a product which analyzed very closely for a disulfonyl chloride derivative of 2-methylthianaphthene. This latter compound formed an amide which gave a very good analysis for a di- sulfonamide of 2-methylthianaphthene and the product had an infrared absorption curve with strong absorptions maxima at 7.19 and 8.h7 p. Other chlorosulfonation experiments on 2-methylthlanaphthene yielded products which gave elemental analysis that were rot in agree— ment with either mono or disubstitution, although the analytical results approached the values for disubstitution more than for a mono- substituted product. A single chlorosulfonation reaction on 2-methyl- thianaphthene conducted at room teuperature resulted only in extreme decomposition and tar formation. 29 By employing the technique of reverse addition of reagents, that is, by adding the chlorosulfonic acid to the alkyl thianaphthene com- pound, it was possible to obtain a monosuhstituted product from 2-methylthianaphthene. The product gave the correct analysis for a mono-sulionyl chloride and a mono ulfonamide of 2-methylthianaphthene. To establish that substitution occurred in the three position of the thianaphthene nucleus during the chlorosulfonation of 2-methylthia- naphthene the product of the reaction was reduced by means of lithium aluminum hydride to its corresponding mercaptan and the latter was then converted to its 2,h-dinitrophenyl sulfide derivative. This sulfide was then compared with the 2,h-dinitrophenyl sulfide of 2-methyl-3-thia- naphthenethiol whose structure has been established by an unequivocal synthesis develOped in the course of this investigation and previously discussed. These reactions establishing the position of substitution in the chlorosulfonation of 2-methylthianaphthene are shown in the following sequences of reactions. I . liE-‘I IL?- ‘J S f I -e++> —--e> Che CS3 n- . SO Cl / ' ClDUcrI 2...: 77 ”4—9 LlAlI‘14 CH3 CH3 O f) A mixed melting point of sa 1Dl€S o; the ¢,h-dinitr0phenyl sulfides prepared by both sequences 01 reaction sio'ec no depression in m altin 5 point. The infrared absorption Spectrum in carbon disulfide of the 2 ,h-dini trophenyl suliide obteilr 3d from the chlorcsulfonated product of 2-methylthianaphthene is shown in Firure VIII. A comparison of the infrared absorption curve with the infrared absorption curve of 2-111"-l31l:;’l- tIlEIdUILHVl-’-\2 i-din'tcopuenvl) sulfide shown in Pi r3 III reveals the identity of these 'wo compounds. An examination of the results obtained from the cl:loros uli'(;nation reactions of various tiianaohchenes indicates that the nature of the product, its purity and yield in such reactions is very dependent on the ex er :nental conditions. The thian naphti'1ene nucleus is quite sensitive towards chlorosulfonic acid. hany of the reactions of thianaphthene and its simple allzyl derivatives were accompanied by tar formation with the resultant develo5nent of excessive quantities of dark colored mat3rial in the reaction solution. Chlorosulfonation does not appear to be practical as a synthetic method in the thianaphtnene series for obtaining the sulf onyl chlorides derivatives needed as intermediates in the preparation of unlinenncuenetnjols. TLeéd-(u, h-Jialtvlanino)ilrvl trianaphthyl sulfides w3r e preparec by the interaction of a basic Solution of the appropriate thiol with an aqueous solution of a tertiary amino alhyl chloride hydrochloride. .1. No particular difficulty was orpe ric need with this reaction, except in n . ~1'n:-...'r‘—= D J-}-\ ’f‘.f‘ ‘ 7' 2-) a iew cases during the pieci ca tion oi the suliiue nyQIOC‘ .L The product would separate from the reaction solution as an oil which El 1 n. N. HHH> mpemam uoEJDm firings—P253553»thin—4251.5»...huzfl : O. a . o N O axon-0.! z. IbOZUJU)! a t n O. NOIBOINSNmfi solidiiied on standing had to be repeated. Isopropyl alcohol in some cases. In others, the O J; was found to be a satisfactory solvent for the i i‘ Sui L- “Vol H t my“ \ L L I, l 7 ,4) snaps. a; aj t ‘1 _ _* 1 wi" uni 13 gas _ 7 ‘1 ,3 , 41" b ’ (1.4 . t s 1 1r CLS s .gwi : 1‘ 05$ . 1L 1' a“; s 1 I ,rcn1 “I ‘_ irg1m in out ALSO- rip- .1 ;t'_-‘ix,. '31; (r , x, r. v 7 3;..,: hLimL ;1 on'a:c,-cri3 Ii'\l‘v pkg-1.1. — 1- i: 4.13)- ’3 1 alum on - :31 L 5’1 4 oi U _1 . s i 2", ,fL A, a1u1 a, ‘7 1,1' LL L':,a EPZLASiS. J :s: or ocunzd . 1. i, o ii M1 ‘Lm'pnaraacologio al evaluation. i‘ixrl','l, ." _"LJL: characizn 1?? CO a *lerental .nwr,‘ y... ' 91.qu v . .HHH nomxomm «. .ow m .comT ope H_L mfl mflmxfl Hoflm we mpsfiompw I Q naoxooad HLQOthmH I w "coapm :Hdp the we pom micm>Hom \ . \ O \ u «1.: ... N3 0H m” We I :5 Hu.em m¢.n mu.au om.em mw.m ea me we gamma He. no 2 o mm e A ecv \ 1 -0 I. J H 0 N44 wa.mm :m.m ms.om ma.mm w: m mm am am muama an mama:w o mm acA :a - ioxl o \ .o. . o) ,,\ 1. N «.NNT‘DH mmq 1| a; :r He.¢ :m or on 0a we.o so mm so w- :a an m; r o z A iov \O O (\J (‘N m 0 \O [\_ LA I C\ 1; \ m -:* O L) (\l (\J -3 O \C) ,\ C’\ O [\ h\ A9 L\_. ! _) C‘ (\l C 3 0 O 0) H&‘ H (.3 CD 02 /'\ N E3 v I Homnaeomea '\ 1 (\J 94 l“ O O V? CC {\- . q—fl "I O\ H H H o \O \C I"\ . LIT I \ N h H , :T I C‘ x (q H \ x O \ «1 mH44¢H cam N. . II No.0m mn.m on mm 0m Ju jw.m mm.mm u MIHQH Homm:Uc u 0 mo 2 A LUV , \o \ 1.1.0 0 o... of \ 34m.” «NH N mus; .14.,u.« I-.4_. I Hm.mm m:.o a1 on 1 mm an m _m ,m we aiucea Hmmm: e o a A sovroronmo .Han 1 f.\ - 0 +1 0 1\ \ a GA” «NH N m” w m N: nl Om.mm 3m.m m©.;u mm mm Om.® gm mm M: blwmfl HmmmL T o m A mDVL A rov \ \\ o .o \ \10 J J 1.1 N :(H NH N m 4 3N NE II He.mm mo.c ca mm mm mm om.m am mm ma m'3mr Ho m: m o a e V: A a: \C ) 1 3 O \ . ll ‘1. ,3, . \\. N .10“ «H AWN 4N ~‘J al on Cm mm.m mo 1m :m.rm d¢.@ ow.mm 0m filmed Hm mne H 0 AW mmv. mtcv m L o m m U UHQHW pedom pamopmm UmpmHSoamo poached pemopem so.m.z mazapom m )wmiov.m whoapo:soo \: m:d :Hadm H> Q£QmQMflgenm:Haxa< nocHEdflmmHmHQVIAJV iii 1‘ it I! .1 .LHH Hosooad HMQOMQooH n m “@onxm «.Qma. soomuogoa no .coa +muaaampmnpomm LL1 cu! mflmMH vv wc¢ -bHom .1+ 0 x O J v \1. O . O , O \ W4 1: PAUL: UH fl.” m4t x4 «m cm c “L “p mu «m ea c mm mm mm anmma r; m, a: 0 mm a A pov: O 1 O . ! C ,J. \1.\\ . l .H I \ :rlu 1 mo wm mg a 59 am CL pm mm L Lo.mm HA m-nvm AL mLomr do an ZNANLO - J,\. O L O .. 0 0A 0 O \.\ \ ib)m Ldflm NLH m \V II «L ya mo w m; Lu mp ca No L HF 0L _ mw mmuoLH AL mL : u a z AcLov . o )o. \o \ o o, o L ix. .1.\-«nw.fi N« I. :» ma mg m mp mu «J ma on 0 9L mm L@ 3mimmm Ho mzumg o m 20A Lav m\.xH xm.é wL.¢1\q:.\4 HH.C HO.3A J: mIQJm Hjmozaomflmag Q zmflmflJ/I rL r\ I! \ C LL . 51 f \ \ .1i 0 , (r. _( Fir? r r. wf hr »L(\ \o .1 1.0 o I o o L N . N wH. N m«« .1 a- II cl mo on mg m NJ mm 1m Hm mm 0 OF mm AF J-NLH Ho mac 2 o m A :DVL Lonwo LH-\J. .11\o J o o \\\ o \ \\ 1 N ON ¢H m“ a...) .40” N 43 l- :L m aw 0 H0 1L jm.am cm 6 ON mm 7L muoma Ho m: m o m A :Lv: A TLV -OJI + o\, o»?\.. ) OJ- _\.0 1 o -. J\ .A1 N 74mH1 1H N W44 .. N N 4 II Mm om m, L 19 w an 00 @ mm :m :u L-AHN Ho m: :0 o m A xoV; A Tov o I o .\ \ o ‘2 o 1\1Jo\,7 . . 3.1 «wmfi N muf ~ :3. N1- I 1. gm «L L aw LL LN om co b 3a «m Lu mumwa Hommzomz u m A :muvroA er m m o m m o Laoflw 0:30L pCcopmm mm pmH50Hwo Prmopmm pamop .o .m.L madfipom m HQHEO 1: .H 031.1 BE mfimém d.r_m%311a1-.1 gamumndmfi Aozdédxfigu > mgmde 35 .HHH .mflxoxm 1.9wq .nome-og0flz an mflmzawm< Hosooa< HhmopaomH I m uncapmNfiHHmpmhpomm how mpco>aom mo.om 4w.m mg.mm HH.mm HO.© mw.mm m.om :p.m mm.mm mg.mm m1.m mo.mm m z o chom pcmohmm m m D UmpmHSOamo pcmohmm Hom.mlm Am oumza Hommzomflmvflo mq ZNAmmov- mp Fumja HummeHmmHo mmAmmovaAmmov- uamflw pcmogmm mo.m.z waszpom m m mmmHmoqmoomawm mmngbm qwmamm mqm<9 LKPdemjflT Halothianaphthene 3-Iodothianaphthene In a two-liter three necked flask fitted with a stirrer, reflux condenser and dropping funnel was placed 700 ml. (7.8 moles) of benzene and 22h g. (1.88 moles) of thianaphtnene. The stirred mixture was heated to 3000. by means of an electric mantel and 270 g. (1.08 moles) Of yellow mercuric oxide and 380 g. (l.h9 moles) of iodine was added alternately in small portions. The reaction mixture was stirred for two hours following the addition of reagents. The solution was allowed to cool to room temperature and then filtered to remove the insoluble mercuric iodide. The dark red filtrate was treated with taree 100 ml. portions of saturated sodium thiosulfate solution to destroy unreacted iodine. The benzene solution was still dark following this treatment. However, a golden yellow colored solution was obtained by use of acti- vated alumina. The benzene was removed by distillation at atmospheric pressure and the residue was distilled at reduced pressure to yield 12h g. (O.h8 moles, 35;) of a light yellow oil which boiled at 116-11500./2 mm. The reported boiling point for 3-iodothianaphthene is 12o-121°c./1.6 mm. (2h). \A.‘ —-\ 1 This compound was prepared using the method employed by Gaertner for the bromination of 3-methylthianaphthene (37). In a 500 ml. three necked flask fitted with a stirrer, reilux con- denser and drOpping funnel was placed lh.8 g. (0.1 mole) of 2—methyl- thianaphthene dissolved in 50 ml. of carbon tetrachloride. The reaction vessel was placed in an ice bath and cooled to 800. To this solution was added over a period of an hour, lé g. (0.1 mole) of bromine con- tained in 25 ml. of carbon tetrachloride. When the addition of the bromine solution was complete the reaction mixture was heated to $000. and the carbon tetrachloride removed with a water aspirator. The residue obtained was stirred overnight at neoc. with 200 ml. of 10; potassium hydroxide solution. The organic layer was separated and the aqueous layer extracted with 2} ml. of carbon tetrachloride. The organic layer was combined with the carbon tetrachloride extract, washed with distilled water and dried over calcium chloride. iemoval of the solvent and vacuum distillation of the residue gave 15.2 g. (0.06? moles, 675) of a pale yellow colored liquid having a boiling point of 125-12ooc./h mm. Calc'd. for CQH7SBr: C, h759; H, 3.11; Br, 35.1”. Found: c, h7.80; H, 3.2L; Dr, 35.h5. k0 (‘1‘ Attempted Preparation of a Grignard Reagent from 3-dromo-2-methylthia- naphthene In an eight inch test tube fitted with a conde ser was placed 0.2L g. (0.01 mo es) of magnesium turnings and 5 ml. of anhydrous ether. F.)- To th 3 mixture was added 2.3 g. (0.01 moles) of 3—bromo-2—methylthia- naphthene dissolved in 1; ml. of dry ether. The reaction mixture was heated at its reflux temperature but the reaction could not be initiated. The deition of a drop of methyl‘iodide produced only a mamcai r" refluxing of the reaction mixture. T‘“ ". :L'11 we" ”licen— tinned. 3-Iodo-2-methylthianaphthene I Ll-ls The method emplovod b3 C.ictner for the iodination of hianapnthene w's used in the synthesis of this material (2h). In a 900 rd. three nec(:. {111d L'drolg'zdc trit‘i 1’; Jul. 0! PM 1‘0 :11101‘ic or was S‘i'fl’il‘at‘lt" ant- C r1. to Congo 5'21? paper ctiv; nercantan—l ,;> CD .3 ’1 -) ll 5% ‘1 J :3 1 .1 a 13. CO c _ LJ. ‘1 LC 0 aqueous solution was extracted ti ried over calcium chloride. rice with 50 vi. portions of d with cold we er and he ether was removed with a water aspirator and the residual dark oil was distilled under recuccd pressure I 3 H.CJCC F! JulT13" V 49 was immersed in an isopropyl alcohol-dry ice bath to lower the tempera- ture of the reaction mixture to —lOOC. The remainder of the n-butyl bromide solution was added over a period of an hour, after which the reaction solution was stirred for an additional hour and a half. The plass wool into a 500 ml. \J n-butyl lithium solution was filtered through three necked flask which had been swept out with nitrOgen and chilled in an ice bath. The filtered n-butyl lithium solution was cooled to 50 ml. of -lOOC. and 26.8 g. (0.2 mole) of thianapnthene dissolved in dry ether was added over a period of twenty minutes after which the reaction mixture was stirred f r an additional hour and a half at -lOOC. The quantity, 6.? g. (0.21 g-atom), of powdered sulfur was added in small portions from a 50 ml. Erlenmeyer flask which was connected to the reaction vessel through a piece of wide rubber tubing. A slight rise in temperature was noted during the addition of the sulfur. The cooling bath was removed and the reaction mixture allowed to warm to room temperature after which it was heated at its reflux terperature for an hour. The reaction vessel was cooled in an ice bath and hydroly- sis of the reaction mixture was carried out with 200 ml. of 2N hydro- chloric acid. The yellow colored ether layer was separ ted and extracted with two 75 ml. portions of 15; potassium hydroxide solution. The combined alkaline extracts were cooled in an ice bath and acidified to (D Congo Red with 2N hyirochlorio acid. An oil separated which SOlidifi d after a short period of stirring. The solid was filtered under a stream of nitrogen, washed with distilled water and dried in a vacuum desiccator. A small portion of the dried product was recrystallized . i p 1 L1. eisul h p ‘ide C: during L le‘d. ~ ‘ o EC'Z'U‘LLI ,‘,,i 7 l ‘ . . i 1 . . . . ; . n ’1. 2 o _1 . 1 nu» - ; ' ) i I , t J a . g . . , o . . melting point of l l 1 q . ,, «r ‘ ‘_ L V . . u 7 . I 7': t «, . . -.— ‘7. t a , . . / '- ‘i .2—ll from isopronyl alcohol. ,1 . 0 r1 U The product was insoluhle in base and recrystallization. r‘ m ’ j__A./‘U. . . T .18,”le , 4 , . \I,“ x, U . L ~‘ If 1 n’, ‘71 u . . « 2:. . . . 7: t.’ T' ' '.l' 843 ha: - , \ '1" u I] o , , , . _ ,L; ~l . . s 1 . . . ‘ , ” “\ T1; ”’1‘ 1 . a :v] a.” 13 mercantan apparently oxidized to ta a Li was allowed to proceed at its reflux temperature for four hours, at tle end of which time, 0.7h g. (0.023 g-atom) of sulfur as added to the reaction mixture. The reaction solution was kept at its reflux tempera- ture for an additional three hours, cooled and then hydrolyzed with 50 ml. of 3N of hydrochloric acid. The yellow colored ether solution was separated and extracted with two 20 ml. portions of 103 potassium w hydroxide solution. The corkined alkaline extracts were cooled and 1" N D acidified with 3n nydrochloric acid. The resulting acidified solution was then extracted with two 25 ml. portions of ether which were then combined, washed with water, and dried over calcium chloride. iemeval of the ether gave about agram of a dark colored solid having a mercaptan lire odor. A 2,h-dinitrophenylsulfide derivative was prepared from this mer- captan and recrystallized from methanol. Its observed melting point was 179-18100. Found: C, {1.93; H, 1.0l5 N, u.l7. ‘W g-I-7et?'1Vl-2—thianapht}:enethiol 7’ n w ~ A v ~ In a 500 ml. three necked ilas? fitted as descrioed ior tne prep- . I aration of 2-thianaphthenetniol, was placed h.5 g. (L.6§ mole) of .. m. lithium chips and lLO ml. of anhydrous ether. The reaction vessel was placed in a dry ice-isopropyl alcohol bath to maintain the temperature .. , o .. . . . r r n ap roxliotely 30 -l§ C. A solution containing hl.l g. (0.; mole) o: redistilled n—butyl bromide dissolved in 60 ml. of dry ether was added P1” ~ dropwise over a period of an hour. ihe reaction mixture was then stirred for an additional two hours, after which, it was filtered through glass wool into a SOD-ml. three necked flask. To the n-butyl lithium solution was added 29.6 g. (0.2 mole) of 3-methylthianaphthene dissolved in 50 ml. of dry ether, over a period of an hour. The resulting solution was stirred for an additional hour, and the 6.7 0 (0.21 g-atom) of sulfur was added at a rate sufii _ent to maintain the reaction temperature between -l§OC. and -lOOC. After adding the sulfur the drv ice-isopropyl alcohol bath was removed and the reaction m wture was heated at its reflux temper ture for an hour. Subsequent] _y, it was cooled in an ice bath and hydrolyzed with 100 ml. of cold 3N hydrochloric acid. The yellow colored ether layer was separated and extracted with two 100 ml. a .. r‘ portions of cold 15% potassium hydroxide selution. -ae combined alk line extracts me e cooled in an ice bath and acidified to Congo Red paper ci" with 3N hydrochloric acid. The dark unpleasan smelling oil which separated was extracted with two 75 ml. portions of etner. The combined ether ezi tra cts there washed with cold water and dried for about a hall an hour over calcium chloride. The ether was removed with a water aSpirator and the residual oil distilled under reduced pressure 00 yield lu.S g. (0.08 mole, h05) of yellow oil boiling at 116-115 OC./2 mm. E) ,4 O r.) :5 (‘1 C) b, ’53 ( l H c! «2 9.: CJ A 2,h—dinitropm ml suliide prepared from tie }-J r‘ r - On m _._ . l- -- i». 21o-2l3 0. alter recrystallization irom metzlano ,4 -w}..,_..___ 3 , 7—bitvet}1fl—2—t1‘1ianapht‘renet: p. 0 HI 1 . 3 , ,. ‘ \_ ‘V L VA [A _. n ,1 .' , f T) I ,. J , ‘C \ . , 7 . r ‘ ~ " ‘ _ , ‘ , \ I n i , (K , ,3 ‘ . 5‘ .. ,A' ' x _ ._ . g . ‘ I , ‘ 1 l1, ‘ ‘ \7 1“- 31 I": M ’ k 1 SiH‘lT.‘L. l1. ‘. i l . v ‘ _ V " 6?] 4 .1: ,31. >. a , . ‘ . v » v: -. 4 e. 7 in}. “, c.. L “¢ ,J“, J ‘. . (l .\.U._ ' . ‘ A ' r~ r. H » ‘ Y 7 my. k '1' , >,.-" c .m, J. edih\ ”a ..,. . ,ul,;. 1 " J7. r L A "x J .' \ _ f‘ ”.1 fflw], 1: lbf' r TI ,7‘ . . .» 1 ‘ ’ i . u v «.w — . 0| -‘ . J 11‘ , . . (L 11" (1! i‘ t . ‘ ”C i L i , 1511. 1‘: r 3 a m. . ,. .1 n1 ‘1 \“,\'.‘ ,4 a v‘ L L. ‘ gt! ' A, . - _ ‘ . , V ‘ r r ‘ -r( .. —. ~ 3 w “' .x - t. -i‘ arr _ \ It .4 i i . .hl . r1 w (.“L L»: ‘3‘ 1.“: . . 111‘ S‘ i '(1 J ‘ $1,,» 3, ‘ ' {A ‘L. 70 ' ’ L, 1191,11," u 1 J .fILY'VV'Z‘l- m, , ’ 1" ’1 £7; '2 ' x: AC" 1, , $3310 ,, 7 I — \ W ; 9.011117; 1“ _- .11 ' m“ v‘ ‘2 I . . L‘ . c _ . (1731/ _ l ‘7, w 1 fl" ,_ 11‘... - F. H W, 4 a, i C H w" r- I, View. .. I ‘ ,1". ‘0 , ‘ ~ ._L . s. , A a . I» , ,\ 2 - 7 ”.7 l H ' ,v» V» ,1 . 7-‘ 1, ., _ J v I _ / r b , ., — , , ’1 1 ". ‘L , A ’Y 7' fl ’ I c'e. $0,. stl‘wcénpsp: u, 33.)” :1, 3.)). . a. ., "" " H ‘ , :_ ‘ . ‘7 v L . i u . .‘ _ 0‘ ° ‘| . ~ I ‘ l ‘ ‘1' :7 7‘ I -> 77" ,. L 7‘ A ‘ _ A s r“ r ‘ . _ 7 ‘ V LY '6“.- \ \ v c . - '7 " \v V \J 7 ..‘ w.) “1‘“, ':, c. x 56 and 15 ml. of dry ether. Two grams (0.008 mole) of 2-methylthianaph- , thenemonosulfonyl chloride dissolved in 75 ml. of dry ether was added gradually over a period of an hour. The reaction solution refluxed vigorously with each addition of acid chloride. The reaction was allowed to proceed at its reflux temperature for three hours. The reaction solu- tion was cooled and hydrolyzed first with water, then with 1N hydrochloric acid. The resulting mixture was filtered througn glass wool and after separating the ether layer it was extracted with two 23 ml. portions of 10% sodium hydroxide. The combined basic extracts were cooled and acidified with 3N hydrochloric acid. The acidified solution was extracted with two 25 ml. portions of ether which were combined, dried over calcium chloride, after which the ether was removed with a water aspirator. The residue consisted of 0.6 g. of a tan colored solid. w . A 2,h-dinitrophenylsulfide der vative was prepared from this product and had a melting point of 181-18300. after recrystallization from methanol. Calc'd. for 015u1004w232: c, 52.01; H, 2.91; N, 8.09. Found: c, 51.83; H, 2.90; N, 8.20. A mixed melting point with the 2,h-dinitrophenylsulfide prepared, .. . . n - . . . ,. , . r on as descrieed aoove, :rom 3-1ono-2-metnyltnianapntnene was 179-181 0. Reduction of Thianaphthenemonosulfonyl chloride In a 150 ml. single necked flask fitted with a condenser, was placed 0.7 g. (0.018 mole) of lithium aluminum hydride contained in 10 ml. of dry ether. To this solution was added over a period of a half hour, l.h g. (0.006mole) of thianaphthenemonosulfonyl chloride dissolved in 30 ml. of dry ether. The reaction mixture was heated at its reflux temperature for three hours and then treated experimentally as described above for the reduction of 2-methylthianaphthenemonosulfonyl chloride. Removal of the ether after drying yielded a few tenths of a gram of dark oil having a mercaptan like odor. A 2,h—dinitrophenylsulfide derivative was prepared and recrystallized ~ from methanol. Its melting point was 160-16200. Calc'd. for 014H60432: c, 50.50; H, 2.h3; N, 8.h3. Found: C, 50.39; H, 2.57; N, 8.20. A mixed melting point of this derivative with the 2,h-dinitrophenyl- sulfide prepared from 3-thianaphthenethiol was 162-16hOC. A mixed melt- ing point of this derivative with the 2,h—dinitrophenylsu1fide prepared from 2-thianaphthenethiol was 130-1u0°c. . 3-Methy1-2—thianaphthene carboxylic acid CH3 CU A small aliquot of the solution containing 3-methyl-2-thianaphthene lithium, prepared during the synthesis of 3-methyl-2-thianaphthenethiol, YW'VFV""‘U"1~. was carbonated by means of dry ice and the white solid obtained after recrystallization from acetic acid melted at 2hl—2h3OC. The reported melting point of this acid is 2h3—2hhoC. (37). 2-Hethyl—3-Thianaphthene Carboxylic Acid COOH CH3 In a 50 ml. round bottom flask fitted with a condenser, was placed 0.2h g. (0.01 g-atom) of magnesium chips and 5 ml. of anhydrous ether. To this mixture was added 2.7 g. (0.01 mole) of 3-iodo—2—methylthia— naphthene dissolved in 20 ml. of dry ether. After a few minutes of initial heating at its reflux temperature the reaction mixture continued to reflux spontaneously. he reaction was allowed to proceed at its reflux temperature for two hours and then the yellow brown reaction solution was poured onto crushed dry ice. The reaction product was isolated in the usual manner, and the crude product was purified by vacuum sublimation. The observed melting point was 192—19300. Its re- ported melting point is 195°C. (36). The yield obtained was 0.6 g. (0.003 mole, 31%). Calc'd. for cloaeogs: c, 62.b7; H, h.20. Found: C, 62.21; H, h.hO. Reaction of Thiaanaphthene with Chlorosulfonic Acid Method A In a 500 m1. three necked flask fitted with a stirrer, condenser and dropping funnel was placed 35 8- (0.3 mole) of redistillcd chloro- sulfonic acid and 25 ml. of chloroform. The reaction flask was immersed in an ice bath and 28 g. (0.2 mole) of thianaphthene dissolved in 25 ml. 59 '\ of chloroform was added dropwise over a period of an hour. The rate 01 addition of the thianaphthene solution was sufficient to kee the m reaction temperature from exceeding 1000. Lhere was an abundant evolu- tion of hydrogen chloride during the addition of the thiandohthene. When the addition of the thianaphthene solution had been completed, 100 ml. of distilled water was added to the reaction mixture. The chloro- form layer was separated, washed witn two 50 ml. portions of distilled water followed by drying over calcium chloride. iemoval of the chloro- form yielded about two grams of a dark oil having an odor similar to thianaphthene. The aqueous layer was neutralized with barium carbonate and the precipitate of barium sulfate was removed by filtration. The resulting filtrate was treated with sodium carbonate until the precipi- tation of the bariunlcarbonate was complete. The barium carbonate was removed by filtration and the pale yellow filtrate evaporated to dryness on a hot plate. The residual solid was dried overnight in an oven at 11000. The weight of the dry, light yellow solid was 35 g. The dry solid was finely ground, and combined with 35 g. (0.17 mole) of phosphorous pentachloride in a 500 ml. three necked flask fitted with a condenser, stirrer and thermometer. The stirred reaction mixture was immersed in an oil bath at 10000. for three hours. The Solid reaction mixture liquified to a dark red solution shortly after being placed in the oil bath. The reaction apparatus was arranged for distillation and the hosphorous oxychloride formed during the reaction . . . . . ,0 was removed by distillation. Its ooserved b0111ng pOint was 103-10u 0. , . . n . . . . e o and the reported (hb) boiling p01nt 01 this material 15 103.3 C. The cooled residue was extracted with 75 ml. of dry benzene and the extract was dried over calcium chloride. The benzene was removed with a Water aspirator to yield 32 g. (0.1h mole) of a dark, yellow colored oil. The yellow oil was placed in a small distillation apparatus and fractionated under reduced pressure. The material proved to be ve. difficult to distill due to excessive foaming and decomposition. The addition of a small amount of Dow antifoam agent did not reduce the foaming. Considerable charring of the material occurred during its distillation. However, a small amount, 5 g. (0.021 mole, 10%) of distillate, which solidified on cooling, was obtained having a boiling point of lhO-lhBOC./2 mm. The green-yellow solid was treated with Norite in ligroin (300-600) and the product obtained on crystallization from the latter solvent was white solid having a melting point of 85—8600. Calc'd. for 03H ( 5028201: C, hl.29; H, 2.17; Cl, 15.2h5 S, 27.56. Found: C, hl.30; H, 2.1h; 01, 15.00; S, 27.h8. A sulfonamide derivative was prepared from the sulfonyl chloride by adding a small amount of it to a beaker containing liquid ammonia. The liquid ammonia was allowed to evaporate at room temperature, and the residual solid was washed with distilled water. The product was recrystallized from boiling water and had a melting point of lSG—léCOC. Calc'd. for CBH702NSZ: C, h5.03; H, 3.31; N, 6.57. Found: 0, u5.1o; H, 3.13; N, 6.u7. Method B To a solution containing 13.5 g. (0.1 mole) of thianaphthene dissolved in 500 ml. of chloroform and precooled to -37OOC., was added 23.3 g. (0.2 mole) of redistilled chlorosulfonic acid contained in 50 ml. of chloroform, over a period of two hours. The purple colored solution was poured onto crushed ice immediately after the addition of the acid chloride was complete. The chloroform layer was separated, washed first with 75 ml. of 10% sodium carbonate solution and then with 100 ml. of water. After drying the neutralized reaction mixture with calcium chloride the chloroform was removed by distillation, yielding 11 g. (0.082 mole) of a dark oil. The oil had a boiling point of 60-62OC./2 mm. and solidified in the received during distillation. It had an odor resembling thianaphthene and formed a picrate which melted at lhé-lhBOC. The reported (M6) melting point for the picrate of thianaphthene is lh8—lh9OC. Reaction of 2-Ketnylthianaphthene with Chlorosulfonic Acid Method A In a 500 ml. three necked flask fitted with a stirrer, dropping funnel and calcium chloride drying tube, was placed 11 g. (0.07h mole) of 2-methylthianaphthene dissolved in 50 ml. of carbon tetrachloride. The solution was cooled to 0°C. in an ice salt bath and 17.3 g. (0.1h8 mole) of redistilled chlorosulfonic acid was added over a period of forty-five minutes. There was considerable decomposition and darkening of the reaction mixture during the addition of the acid Chloride. and the sulfonyl chloride obtained in method A was 115—11600. indicating the two compounds to be identical. Method C To a solution containing 11 g. (0.07h2 mole) of 2-methylthianaphthene dissolved in 75 ml. of chloroform and cooled to 000., was added 26 g. (0.223 mole) of redistilled chlorosulfonic acid over a period of an hour. The resulting reaction mixture was stirred for an additional hour and then poured onto 500 g. of crushed ice. The chloroform layer was separated and the aqueous layer extracted with two 75 ml. portions of chloroform. The combined extracts were washed with three 50 ml. portions of ice-cold water, dried over calcium chloride, and then combined with the original chloroform layer. Removal of the chloroform with a water aspirator left an impure solid product which was recrystallized from ligroin to yield 3 g. (0.012 mole, lo.h%) of a crystalline, white solid having a melting point of llS-ll6OC. A mixed melting point of this material with the product obtained in l-Iethod A was 115—11700. Method D To 9h g. (0.8 mole) of redistilled chlorosulfonic acid at 1000. was added over a period of two hours, 30 g. (0.2 mole) of 2-methylthianaph- thene dissolved in 25 ml. of chloroform. The reaction mixture was stirred for a period of four hours at 0 to 10°C. and then for an addi— tional two heurs at room temperature at the end of which time it was poured onto 1000 g. of crushed ice. The aqueous solution was extracted with two 100 ml. portions of chloroform. The combined extracts were washed with two 50 ml. portions of cold water dried over calcium chloride and combined with the original chloroform layer. Removal of the chloro- form yielded a small amount of a dark oil which solidified on being set aside at room temperature for several hours. This solid, after it had been recrystallized from dilute ethanol, melted at 120—12200. Calc'd. for monosulfonation, CQPgOQSgCl: C, h3.81; H, 2.86; c1, 1o.37. Calc'd. for disulfonation, 09360453012: 0, 31.30; H, 1.75; Cl, 20.5h. Founi: C, 31.86; H, 2.27; Cl, 18.93. A sulfonamide derivative was prepared from this product and concen- trated ammonium hydroxide. The melting point of the amide after recrystallization from dilute ethanol was 265-76700. Calc'd. for monosulfonamide, CQHQORESO: C, h7.555 H, 3.99; N, 6.16. Calc'd. for disulfonamide, 09H1004N283: C, 33.28; H, 3.29; N, 9.1h. Found: C, 3h.90; H, 3.21; N, 8.57. The aqueous layer from the hydrolyzed reaction mixture was neutral- ized with sodium carbonate and evaporated to dryness. The resulting salt mixture was finely ground in a morter and then stirred vigorously for eighteen hours with 500 ml. of boiling methanol to extract the sodium salt of any sulfonic acid present. The solution was filtered to remove undissolved solid and the methanol was removed by distillation. . . , . . . - . . . ,o , The solid obtained weighed 21 g. alter crying in an oven at 110 C. for three hours. 1 o -1 The presumed so~1um sulfo onate ootained as described. aoove was Q combined with 33 . (0.17 mole) of phosphorous pentachloride. Aiter C) .J. stirring the solid mixture a few minutes it liquified to a dark red solution. This solution was stirred for four hours at 1000 0., cooled and extracted with two 75 ml. portions of benzene. The cohbined benzene extracts were washed with three 23 ml. portions of cold water, and then dried over calcium chloride. Removal of the ‘enzene yielded 1h g. of a dark red oil. Attempted vacuum distillation of a small portion of this oil only resulted in e :tensive decomposition. When a small quantity of the oil was treated with conceW1ated ammonium xycrO}ide it gave a gummy material whi01 could not be purified The remainder of the oil was allowed to react with lithium aluminum hydride using the following experimental procedure. To 6 g. (0.16 mole) of lithium aluminum hydride dissolved in 75 ml. 0f QNHTCTOUS‘3313T: under a nitrogen at ioopno was added over a period of an hour to 10 g. of the oil contained in 25 .r. . of dry other. As each drop of the g V other solution came in contact with the hydride solution, large quanti- ties of wiioe fumes were evolved. Solid material was deposited on the walls of the reaction vessel, on the surface of which Sparking occurred during the reaction. This expel riment was discontinued when the sparking became more fr eqrent as the reaction proceeded. hethod 4 To a solution containing 11 F. (0.07h mole) of 2-methyl-thia- .3 1 p 1 a [V :3 w H -1" ,, ‘ j ‘ J— _I_ ‘ J- _ r ‘I " ‘ f‘. ' " 0 7‘1 naphthene in 30 ml. oi Chloroiorm and xepo ao room oompeiature (23 c.) was added 17.3 g. (0.1ho mole) of redistilled chlorosulfonic acid r/ 0:) dissolved in 30 ml. of chloroform. As the addition of the acid chloride proceeded, a black tarry material formed in the reaction mixture. In a short time the entire reaction solution was converted to a black, N1 gmnmw'like substance. The reaction was discontinued at this point. Method F To 25 g. (0.21 mole) of redistilled chlorosulionic acid precooled to -l5OC., was added over a period of forty-five minutes, lh.8 g. (0.1 mole) of 2-methylthianaphthene dissolved in 35 ml. of chloroform. The reaction solution took on a dark brown color almost at once. The re— action temperature varied between —lYOC. and -l§oC. during the addition of the 2—methylthianaphthene. Large quantities of hydrogen chloride were evolved during the reaction. The dark reaction solution was poured onto 500 g. of ice immediately after completing the addition of the 2-methylthianaphthene. The chloroform layer was separated and the aqueous layer extracted twice with 50 ml. of chloroform. The combined chloroform extracts were washed with 50 ml. of cold water, dried over magnesium sulfate and combined with the criminal chloroform layer. The chloroform was removed with a water aspirator, yielding a yellow colored oil which solidified after being set aside for a few minutes, at room teLperature. The product was recrystallized from a mixture of equal volumes of ethanol and cyclohexane. It had a melting point of 161-1630C. and weighed 6 g. (0.016? mole, 16.7%). This material gave a positive sulfur test and a negative halogen test after carrying out a sodium fusion of the material. 67 Calc'd. for a sulfone, 0133140283: C, 60.33; H, 3.9h; S, 26.86. Found: C, 59.71; H, b.155 S, 26.72. loaction of 3—Methylthianaphthene with Chlorosulfonic Acid In a 500 ml. three necked flask fitted with a stirrer, condenser and dropping funnel, was placed 93 g. (0.8 mole) of redistilled chloro- sulfonic acid. The acid was cooled to 1000. and 15 g. (0.1 mole) of j-nethylthianaphthene was added over a period of an hour. The solution became almost black during the reaction, and copious quantities of hydrogen chloride were evolved. Stirring was continued for fifteen minutes after the addition of the 3-methylthianaphthene was completed. The reaction mixture was then poured onto 1000 g. of ice. The aqueous solution was extracted with two 100 ml. portions of chloroform. The combined extracts were dried over calcium chloride. Removal of the chloroform yielded only a trace of a dark oil. The aqueous solution was neutralized with barium carbonate, filtered to remove the precipitated barium sulfate, and the filtrate treated with sodium carbonate until the precipitation of barium carbonate was complete. The solution was filtered and the filtrate evaporated to dryness. The solid residue was dried at 11000. for four hours. The dried solid, weighing h3 g., was combined with h2 g. (0.2 mole) of phosphorous penta— chloride contained in a 500 ml. three necked flask, fitted with a stirrer, condenser and thermometer, and stirred vigorously. The mixture liquified and was heated at 100°C. for an hour and a half. The dark red solution was cooled and poured onto 100 g. of ice. The aqueous solution was extracted with two 50 ml. portions of benzene and the extxacts were washed with two 25 ml. portions of cold water. The washed benzene extracts were combined and dried over calcium chloride after which the benzene was removed with a water aspirator. The tan colored residue, 7.5 g. (0.022 mole, 22;), was recrystallized from ligroin following prior treatment with Norite. The purified material had a melting point A ’0’1 01 107-109 C. Calc'd. for monosulfonation, CQH7028201: C, h3.Sl; H, 2.66; Cl, 1h.37. Calc‘d. for disulfonation, 09H604SSCl2: C, 3l.303 H, 1.75; Cl, 20.5u. Found: c, 31.us; H, 1.95; Cl, 20.22. A sulfonamide derivative was prepared from the sulfonyl chloride by boiling a small quantity of it with concentrated ammonium hydroxide for five minutes and then evaporating the reaction mixture to dryness. The crude product was washed with cold water and then recrystallized. from boiling water. The me tin; point of the amide was 258-26000. r42. Calc‘d. for monosulfonamide, CghgozNSB: C, h7.>>; H, 3.993 N, 6.16. Calc'd. for disulfonamide, 09H1004N283: C, 35.26; H, 3.’93 N, 9.1h. Found: C, 35.2u; H, 3.30; H, 8.85. (J-(fl,N-Dialkylamino)Alkyl Chlorides H"droghlorides €LPiperidinoethyl Chloride Hydrochloride < :N-CHZCHBCl. HCl In a 500 ml. three necked flask fitted with a stirrer, reflux condenser, and dropping funnel were placed, 65 g. (0.5 mole) of €§~piperidinoethyl alcohol. A slow Stream of dry air was drawn through the apparatus during the reaction. To the reaction vessel was added a solution of 72 a. (0.6 mole) of redistilled thionyl chloride dissolved Q in 100 ml. of dry chloroform at a rate sufficient to maintain the reaction temperature between 50 and 5500. The solution was heated at its reflux temperature for a half hour following the addition of the thionyl chloride solution, which required two hours. The reaction solu- - tion was cooled and the solid collected or filtration, washed with cold ether and dried in a vacuum desiccator. iecrystallization from absolute ethanol gave 60 g. (0.32 mole, 66;) of a product having a :elting point ‘I {\‘n 0 _-~- , __c n .1. .f. u‘ o ‘ o o , ~\“-O of 206-208 C. The reportec melting pOlnb ior this material is 2 t C. (L7). X‘Tiperdino-n-propyl chloride hydrochloride T '." 01'" f" T f‘ T?” Ei‘CiIPK/AIPUEL ‘J .JLU fl 1 ~ The method of Adams and Whitmore was employed in the preparation 9 - o J— . ' C) of this material (he). In a two liter three necks flask fitted with a stirrer and reflux condenser, was placed lh2 g. (0.9 mole) of trimethylene chlorobromide, d) h00 ml. of dry benzexe, and 119 g. (l.h moles) of piperidine. Th solution was stirred intermittently for a half hour, during which time the reaction solution began to refl x. After the refluxing of the 70 reaction solution had terminated, external heat was applied to keep it at its reflux temperature for three hours. The reaction solution was cooled and the piperdine hydrobromide was removed by filtration and washed with dry ether. The ether washings were combined with the benzene solution and extracted with three 123 m1. portions of 3N hydrochloric acid. The combined extracts were made basic with lUN sodium hydroxide and the oil which separated was extracted with three 100 ml. portions of ether. The ether extracts were dried with magnesium sulfate and then treated with dry hydrogen chloride gas. The resulting precipitate was recovered by filtration and dried in a vacuum desiccator. The crude product on recrystallization from absolute ethanol yielded 89 g. (O.h§ mole, 50%) of white solid melting at 217-21900. The reported melting point for this salt is 220°C. (49). Glebrpholinoethyl chloride hydrochloride 0‘ hFCHZCHQCl.HCl To 52.5 g. (O.h mole) of ‘!-morpholinoethyl alcohol dissolved in 150 m1. of chloroform was added over a period of an hour, 60 g. (0.5 mole) of redistilled thionyl chloride dissolved in 73 ml. of chloroform. The product separated from solution during the addi'ion of the thionyl chloride. The reaction mixture was stirred for fifteen minutes after the addition of the thionyl chloride was couplets and then filtered. The crude product was washed with dry other and dried in a vacuum 1 desiccator. Recrystallization of the crude product from absolute etianol DI] gave 38.7 g. (0.21 mole, 52$) of a white solid having a melting point I." r F I: on 1 \' ,L 1 1 o .',r~ ‘.,- 0,. 01 l{y-lol o. The reported Ieltin point i'or this COIHpo 1nd is lez-lt2.; c. )thorpholino- n-propy l chloride hydrochloride PI—C:{ECE{B UL. ”7721,14ch { In a three liter three necked flask fitt i with a reilux condenser, dropping runnel and stirrer was placed 300 g. (3.hh moles) of morpholine, 300 r. (2.29 moles) of trimeth;vlen:3 chlorohromide and 900 ml. of dry C) " benzene. 1he reaction mixture was allowed to stand at room temperature I I ,1 .‘ for an hour with occasional stirring. The temperature C: the reaction mixture was raised to its rejlux temperature and then the heat we 1 emoved, after which 'ne reaction mixture rejluxed spontaneously ior L about a half hour. External heat was a'ein applied and t;31 reaction mixture was liep t at its re flux temperature for thre ehours, cooled, and the insoluble morpholine hydrobromide removed by filtration and washed with drv ether. The ether wals in s were comoinC-d with the benzene filtrate and the resulting solution was extracted with 101r 200 ml. portions of EU hydrochloric acid. The c mbined acid Itracts were made A .a‘ basic with 10h sodium hydroxide resu1tin in the separation of an oily Cl layer. The aqneous layer was extracted with 100 ml. of ether. The comoined ether extract and oil IWJPO dried ov er anhydrous sociuxx sulfate Gaseous hydrogen chloride was passed slowly into the chilled ether soluticn to 1orm the insoluble amine hy‘rochloride which was filtered a- — '— 4"," _,,.u and wasned with dry ether. After recrystallization from isopropyl alcohol, 275 g. (1.37 moles, dug) of a white Ciystalline material was . . . .. . . . 1 , o . , . . . Obtained wnicn melted at 160-102 C. The reported melting p01nt for this substance is 168-17000. (AB). Q-Tlxiodiglycol ,cwzcnaoa \CHBUHZOH In a three liter three necked flask fitted with stirrer, reflux condenser and thermometer was placed 298 g. (3.7 moles) o: ethylene chlorchydrin and 1200 ml. of distilled water. To this solution was added h93 g. (2.05 moles) of sodium sulfide over a period of forty—five minutes. The temperature of the reaction mixture was maintained at about 3000., while it was stirred for a half hour after the addition of the sulfide was complete. The reaction solution was then heated to 90°C. on the steam bath for forty—rive minutes, cooled, and neutralized to tumeric paper by adding concentrated hvdrochloric acid dropwise. The water in the reaction mixture was removed by vacuum distillation and the residue extracted twice with 500 ml. portions of hot absolute ethanol. The combined yellow colored alcohol extracts were returned to the three liter flask and the ethanol removed under reduced pressure. The residual oil had a boiling point of lSh-lSGOC./9 mm. and weighed 199 g. (1.63 moles, 885). The reported boiling point of fie-thiodi- glycol is 16h—16600./20 mm. (51). 73 e , Q' —Di‘oromodiethy1 sulfide n: {w 31‘ ’u: 1.2.1112 r‘l" «‘1; e vflnu;1»Bl' ‘4 K. To 25 g. (0.21 mole) of . condenser and dropping lunnel was placed 200 g. (0.ol mole) 01 Q,Q-di- bromodiethyl sulfide and 900 ml. of chloroform. To this solution was added rapidly, lhB g. (2.u2 moles) of monoethanolamine. The reaction mixture was heated while being stirred on the steam 21th for iijteen hours. After cooling, it was filtered and the precipitated ethanol amine hydrobromide extracted with two 75 ml. portions of chloroform. The combined chloroform extracts and original chloroform filtrate were chilled and treated with gaseous hydrogen chloride. The hydrochloride product was filtered, washed with a small portion of dry ether and dried in a vacuum desiccator. Recrystallization of the product from absolute ethanol gave 93 g. (0.51 mole, 63p) of a white crystalline solid having a melting point of 159—16100. The reported melting point of this salt is 162-16300. (9). GP-Thiomorpholinoethyl chloride hydrochloride I \ - s N-CHZCH231.H01 \....l A suspension of 1h g. (0.076 mole) of ‘P-thiomorpholinoethyl alcohol hydrochloride in 75 ml. of chloroform was heated to hOOC. on a steam bath. To the heated solution, was added 9.5 g. (0.08 mole) of redistilled thionyl chloride dissolved in 15 m1. of chloroform at such a rate as to keep the reaction temperature below 3500. The reaction mixture was heated at 5900. for a half hour after the addition of thionyl chloride was complete. After cooling, the solid was removed by filtration and washed with cold, dry ether. The crude product was treated with Norite in isopropyl alcohol, filtered, and allowed to crystallize from the isopropyl alcohol. The yield of pure product was 75 6 g. (0.03 mole, hOfi) and it melted at 203-2Oh00. The reported melting point of this substance is 206-20800. (S3). XLThiomor holino-n-propyl chloride hydrochloride S KCHECHECH201.HCl \.__.l A mixt re of 137 g. (0.55 mole) of 9,e'-di‘oromodiethyl sulfide, 500 ml. of chloroform and 12h.h g. (1.66 moles) of zr-propanolamine was heated at its reflux temperature on a steam bath for eight hours. The steam bath was removed and the reaction mixture was stirred overnight. The hydrobromide of the amino alcohol which had formed in the reaction was removed by filtration and washed with chloroform. The chloroform solutions were combined and then the chloroform was removed by distilla— tion, yielding 81.6 g. of a yellow colored oil. To this crude —thio- morpholino-n—propyl alcohol (9) dissolved in 1C0 m1. of chloroform at room temperature, was added 63 g. (0.53 mole) of redistilled thionyl chloride dissolved in 50 ml. of chloroform over a period of an hour. The dark reaction solution was heated at its reflux temnerature for a half hour after the addition of the thionyl chloride had been completed. The reaction mixture was cooled and 150 ml. of distilled water was added to extract the hydrochloride. The aqueous extract was made basic with 20% sodium hydroxide and the yellow colored oil which separated was extracted with ether. The ether extract was washed with cold water and dried over calcium chloride. The ether solution was chilled and then f- I] Tr The ether extracts and oil were combined and washed first with a 10% sodium hydroxide solution and then with three 25 m1. portions of cold water. After drying the ether solution of the product with anhydrous magnesium sulfate it was cooled in an ice bath and treated with a gentle stream of dry hydrogen chloride until there was no further precipitation of andne hydrochloride. The use of excess hydrogen chloride was carefully avoided as it usually resulted in the formation of a very sticky product or a product which separated from the ether solution as an oil. The white precipitated product was collected on a Buchner funnel and washed with a small quantity of dry ether. Recrystallization of the hydrochloride from isopropyl alcohol gave 8 g. (0.029 mole, 89;) of a white crystalline product which melted at 16h-16500. Calc'd. for 012H16N8201: C, 52.63; H, 5.89; S, 23.h2. Found: c, 52.89; H, 6.02; 8, 23.31. @m(Diethylamino) ethyl—2—thianaphthyl sulfide hydrochloride I l /C"‘H5 S-CHQCHQN . H01 “ H 2 5 Following essentially the same experimental proéedure as described above, 8.3 g. (0.05 mole) of 2—thianaphthenethiol was dissolved in a solution containing 7.2 g. (0.18 mole) of sodium hydroxide contained in 30 m1. of distilled water. To this solution heated to its reflux temperature was added 6.9 g. (0.0h mole) of Q-xfiethylaminoethyl chloride hydrochloride dissolved in 30 ml. of water. The addition of 80 isolated as previously described. Recrystallization of the hydro— * p 32;) of chloride salt irom isopropyl alcohol gave 6.5 g. (0.021 mole, .. .\ .. .. \ n10 a wnite solid whicn melted at 101-105 C. ,1 . ”a q n T. — , fl , a. Calc'd, For u..h.h(vfinhl: H. u?,??; H. L,7w: w ?0 x0, . . ‘ 0 . - ‘ g o f I c . Y- - _ w _ _. :y.- 1‘ x . i. 'w.. K .. J \__4/ f7 '5' ‘ ‘ i. "I" T 7“ r ‘V' 1 ‘a' V' , . x" t x , < '. . . I J —‘ r ».K V ‘rr ' 'r, L ;M . . ‘\ r‘ V V .1 (v, _ ‘ ‘/‘ i. i ll . \ m , < t .3 ct - 7 ”1 ‘” i f 0 J ' n . I d / ‘U (7; 1 r ‘> , . ‘V . Y _ v t w __ _‘ .. ,7“ (- | . r ‘ , ,r. t ,. ,, 7 fl .1 k, \ i e) . i), _x . , I . ,,,,, m , . r .’:“I 4”; ’1 , ‘ I ‘11.“: ( IT‘S. ,,,,,,, :3 ‘7 Ln. . ‘-[’~'\ UC f ‘r‘.V . a Q \n w ‘ I ll s} U .. . c 'L, " A . u “I v \ . . z ‘ . , gr i . ‘ . . .1 La 1‘, . . / yr) I ‘ c a '. ALHIAk - 7/. . q . . '0 U, 7 . . .. . .higb‘, Irwnfism- lil’l’ ’1 81 E3-Piperdinoethyl-2-thianaphthyl sulfide hydrochloride I I SCH20H2N: > .HCl To a solution of 6 g. (0.15 mole) of sodium hydroxide in 75 m1. of distilled water, was added 8.3 g. (0.05 mole) of 2-thianaphthenethiol. This solution was brought to its reflux temperature and 8.3 g. (0.0h5 mole) of @r-piperdinoethyl chloride hydrochloride dissolved in hO ml. of distilled water was added over a period of a half hour. The reaction solution was kept at its reflux temperature for six hours after which the desired amine salt was isolated as previously described. Recrystal- lization of the product from absolute ethanol gave 10.5 g. (0.033 mole, 7h.5%) of a white solid which melted at 220—22200. Calc'd. for C15H20N5201: c, 57.39; H, 6.h2; 3, 20.53. Found: c, 57.57; H, 6.53; s, 2o.h6. X'-Piperdino-n—propyl—2-thianaphthyl sulfide hydrochloride l I SCH20HQCH2N: > .HCl The experimental procedure used in this preparation was the same as that already described. The quantity, eight grams (0.0h8 mole) of 2-thianaphthenethiol was dissolved in a solution made from 6 g. (0.15 mole) of sodium hydroxide and 75 ml. of distilled water. This alkaline solution of the mercaptan was brought to its reflux temperature and 8 g. (0.0h mole) of \f—piperdino-n-propyl chloride hydrochloride dis- solved in 30 ml. of water was added over a thirty minute period. The resulting reaction solution was kept at its reflux temperature for three hours and the product was then isolated as previously described. Recrystallization of the product from isopropyl alcohol gave 6.5 g. (0.02 mole, u9.55) of a white solid which melted at luo-ldaoc. Calc'd. for ClSHZZNSZCl: C, 58.60; H, 6.76; S, 19.56. Found: c, 58.50; H, 6.71; s, l9.h1. (3-Thiomorpholinoethyl—2-thianaphthy1 sulfide hydrochloride I | . m . oh20H2w S. H01 5 \L__J/ A 6 g. (0.036 mole) quantity of 2-thianaphthenethiol was dissolved in a solution prepared from 6 g. (0.15 mole) of sodium hydroxide and 75 m1. of distilled water. To this a kaline solution of the sodium salt of 2—thianaphthenethiol was added 6.7 g. (0.033 mole) ofGB-thio- morpholinoethyl chloride hydrochloride dissolved in hO m1. of distilled water, over a half hour period. Heating this reaction mixture at its reflux temperature for five hours resulted in the formation of the free amine as an oil. This was isolated and converted to its hydro— chloride following the experimental procedures already discussed. Recrystallization of the product from isopropyl alcohol gave 7 g. (0.021 mole, 6h%) or a white solid which melted at 191-19300. Calc'd. for 014H15Nsacl: C, 50.66; H, 5.h7; S, 28.98. Found: 0, 50.75; H, 5.5t; 3, 29.17 83 X'-Thiomorpholino-n—propyl-2-thianaphthyl sulfide hydrochloride I I SCH20H20H2H /r_—‘\S HCl 5 \c__o/ ' The previously described experimental procedure was used for the preparation of this material. An 8 g. (0.0h8 mole) quantity of 2-thia- naphthenethiol was dissolved in a solution prepared from 6 g. (0.15 mole) of sodium hydroxide and 75 m1. of distilled water. This alkaline solution was brought to its reflux temperature and 8.6 g. (0.0h mole) of Y'-thiomorpholino-n-propy1 chloride hydrochloride contained in 50 ml. of distilled water was added over a period of a half hour. The reaction solution was maintained at its reflux temperature for two hours after which the product was isolated by methods previously described. Recrystallization of the amine hydrochloride salt from iso- propyl alcohol gave 9.2 g. (0.027 mole, 77%) of a pure product which melted at 123—12toc. Calc'd. for C15H20N5301: C, 52.07; H, 5.83; S. 27.80. Found:' C, 51.89; H, 5.62; S, 27.51. 8-Jhmethy1aminoethyl-3-methy1-2—thianaphthy1 sulfide hydrochloride CH3 //CH3 SCHBCH2N\\ .HCl H3 This compound was prepared according to the previously described experimental procedure by combining 8.2 g. (0.0h5 mole) of 3-methyl-2- thianaphthenethiol and 6 g. (0.15 mole) of sodium hydroxide dissolved ' l.‘ r" 1’ .. .tter Wlufl :.0 t ‘7‘ k; 7.1 in 75 m1. of distilled aminoethyl chloride hydrochloride .a L" .,. rUllu“ "1‘1 . .. 1 a n ‘11 . I.‘ 1‘ .113 L l J. (3,. 111.11. LA ,. . 3\ c \ . a - at l‘—y., ,. ‘ . .l‘ . .I a, v . 1t ' - .. I o , 5 . , ~- 4 a ‘ . a . ’V . ‘ ’1‘ . ',111_.- J. 1,. ; . . ,5 .3. L .. @-,~. 2 . ;__ —_ -5» ‘7 I I 7. 1 Jv‘ ’: 4 . ,‘. "‘ . ,. 4‘... .1, . ,\\ .. 1 . d ,7 r ,4 . . . . 3 _. (4153130,! 7 :3in 11". 3 3". ,LL 0 1111 7?" 3'. If." ‘1' L1"! ’1 n. r * - '7 w. 2.. t I : u . I . <1 , u r-v’ 1:1.“ ‘7 ‘1 , , 1,. , , o if? . ,.7 J .1. {r . ‘o . p 1' ”I' 17,-.4 .1. '1 ' ' V ‘ I ,dLr'H. 01.19, 1,: o. «~.. ,',-~ .o 1‘ .'. ’.(- } ’ (To ‘4 "‘7‘, realm... .3. .,.:,., ,, 1.1.), u, ....‘ —-1 lethylamino-n—propyl-B—m3thy —2—thianaoh hyl sulfi ”. 1 Ft" 1‘ C‘ ‘ '3 ‘ . . . l .. r u 7 I I A V , . .ne—n-y~ony. c J.YH a de< to the alk ‘0‘ ”a". , _‘ 1 ’ . o .. ., . . . a 1; m: ,. ~. '3',‘ .Jr- l_. . 2e hvoroch 1 » a v w 3. WV VH1 r ’ _ 1 st). .0 .111} .e prior treatment nt of .""" “amt—n 86 sodium hydroxide and 75 ml. of water, a second solution prepared from 6.3 g. (0.0h mole) of dimethylaminoisopropyl chloride hydrochloride and to m1. of water. The resulting reaction solution was kept at its reflux temperature for a period of four hours. Recrystallization of the crude hydrochloride product from isopropyl alcohol gave 8.9 . (0.03 mole, 7h%) of a white solid which melted at l72-l7hOC. Calc'd. for CléHZONSZCl: C, 55.70; H, 6.68; S, 21.2h. Found: C, 55.82; H, 6.88; S, 20.95. @ -Morpholinoethy1-3 -methyl-2 -thianaphthyl sulfide hydro chloride CH3 l l /—\ SCHZCHZN 0.HCl \u__4/ The experimental procedure used in this synthesis was the same as previously described. The mercaptan 8.2 g. (0.0h5 mole), was dissolved in a solution of 6 g. (0.15 mole) of sodium hydroxide contained in 75 m1. of water. The alkaline solution was heated to its reflux tempera- ture and 7.11 g. (0.01; mole) of @ —morpholinoothyl chloride hydrochloride dissolved in hO ml. of water was added over a thirty-minute period after which the reaction solution was kept at its reflux temperature for four hours. Following the isolation procedure used above, the crude hydro— chloride was obtained and following recrystallization from isopropyl alcohol gave 5.5 g. (0.017 mole, h2fl) of a white solid which melted at 200-20200. Calc'd. for 015H200K8201: c, 5h.615 H, 6.11; s, 19.hh. Found: 0, 5u.68; H, 6.39; S, 19.72. @ -Pipor dine ethyl—3 —1r1etlly1-2 -thianaphthy1 1 1‘ ‘.< a, .71 ~11.” .7 ,1 T" 7...... , x . ,1 : 1, . ’. I . “1 A ,1 f‘ -1‘ 3 m» ‘ 1 ~71 1 1 1 ‘ 11 1‘ ‘ .)L1 1 1 1 1 1 1 (1 ._1 ‘ 1.; S, ‘ ‘ X ' ' 1 1 . .1 1~ 1,-11 a: x 1 \1' 1".1t1 —11_1,,1\ 1,1, 1_ 41 m '1‘, -, 1 '1 ,. 1 1 151. .11” 1 . 1 1 11 V'Iu , _ 1.1 ,7 ‘ . _ 1 . 1 ; A I ‘ 1 1' 1 . . a . ( \ ‘ 5 . . 1 . >0 ‘\ . _ 1 . 1 '1 ' 1. 1 " h ‘ ,. 1 a" 1 . . . , 1 1 11.1 .. x11 1 " e _. ' ‘ 1» ~ 11 \ I 1 l ‘ I 1 ‘ 1 l J 1 11 1] 7' , 1 , 1 1: .r1 ,1 1. 1’ a. ., 1 1 , .11. 1 . r 111 11. l ‘ '1 1 1, I: . 17 ‘1 “1.1 '10 1 L‘ " 113‘ . 1’ 1_1 .' D11 1 1 311‘” {1‘1"1 ‘1 :11 11 1 i ".1 1_ 1', ' 7 . 12‘ ' ‘ I 11 1 3 I‘ .1 "1 5‘ o . 1‘ 1 1 .1 1. {11 _1 :1111 1. 1 "1.1 . 1. . . 1. 1 ,,‘ 1 . ' ,.1 . 1111111,I11. 1111 13,,.11,A,1.1..)..._11_. » . ,11, 1 , ~ 1 1. . o '7 “(1 . . 111,111. ‘11: 1. ; q ‘o J, )g ‘I o/ . -.« .71 T1" _:1_ 73:1,». ’,,—"".‘I. 1;“ 1_ (":7' 1118"" ,1 . 1.1.91.7 1 1, ‘ ""11, 1. 1 ,‘1'71'. o 1 ;-1 1 x .1 .7 1“ 1, 1 ’ 11 1.; 11 “11-1 'L',11’. ;111 .1 1,11” 1;. < : m, " i {'1 1 .. p 1 1 ‘ ‘ {5111' 8‘ El ,. 1) temperature for three and a half hours and the product isolated in the manner described earlier. The crude hydrochloride product was recrystal- lized from isopropyl alcohol after prior treatment of its alcoholic solution 11th Norite. The yield of the product was 9.3 g. (0.027 mole, 68S), and its observed melting point was 160-16200. Calc'd. for 017324U5201: C, 59.71; H, 7.07; S, 18.75. Found: C, 59.h9; H, 7.05; S, 18.66. G?-Thiomorpholinoethyl-3-methyl—2-thianaphthyl sulfide hydrochloride 0H3 I " 'v y o0n20H21 S-hCl 5 \___/ A solution containing 3 g. (0.075 mole) of sodium hydroxide in f O 50 ml. of water was prepared and to it was added 2.7 g. (0.015 mole) 3—methyl-2-thianaphthenethiol. A solution prepared from 3 g. (0.015 mole) of Q—thiomorpholinoethyl chloride hydrochloride in 30 ml. of water was added over a half hour period. The resulting reaction solu— tion was heated at its reflux temperature for three and a half hours and then the product was isolated as previously described. Recrystal- lization of the crude hydrochloride product from isopropyl alcohol yielded 2.6 g. (0.0075 mole, 515) of a white solid which had a melting point of 206-20800. Calc'd. for ClSHZONSSCl: C, 52.07; H, 5.83; S, 27.80. Found: C, 51.87; H, 6.02; S, 28.05. I ‘ll I'lll‘ lllllll 89 If-Thiomorpholino-n—propyl—3-methy1—2-thianaphthy1 sulfide hydrochloride CEIB l l v. .7 f“\ s \___/ This compound was prepared by adding to a solution containing 8.2 g. (0.0h5 mole) of 3-methyl—2-thianaphthenethiol, 6 g. (0.15 mole) of sodium hydroxide and 75 ml. of water, a second solution prepared by dissolving 8.6 g. (0.0h mole) of 31thiomorpholino-n—propy1 chloride hydrochloride in hO ml. of water. The resulting reaction mixture was kept at its reflux temperature for four and a half hours. Following the same procedure described above, the crude hydrochloride product was isolated and recrystallized from isopropyl alcohol to yield 9 g. (0.025 mole, 62%) of a material melting at 126-12800. Calc'd. for 015H22N3301: c, 53.38; H, 6.16; 5, 26.72. Found: c, 53.52; H, 6.30; s, 26.hh. (g-{hrethylaminoethyl—3-thianaphthyl sulfide hydrochloride. CH3 // ‘CHBCHZN’/ ~H0 \\,. 0&3 ‘\ S Following the previously described experimental procedure, the quantity, h g. (0.02h mole) of 3—thianaphthenethiol was added to a solu— tion containing 2.h g. (0.06 mole) of sodium hydroxide dissolved in 50 ml. of water. The alkaline solution was heated to its reflux temperature and 2.9 g. (0.02 mole) of Q-«fimethylaminoethyl chloride hydrochloride contained in 30 ml. of water was added over a half hour period. 90 The reaction mixture was heated at its reflux temperature for three hours, cooled and the product isolated as already described. Recrystal— lization of the crude hydrochloride product from isopropyl alcohol following prior treatment of its alcoholic solution with Norite, gave u g. (0.015 mole, 733) of a white solid which melted at 1u5—1u700. Calc‘d. for ClelastCl: C, 52.63; H, 5.89; S, 23.h2. Found: c, 52.73; H, 6.01; 5, 23.11. @ -1~Iorpholinoethyl-3-thianaphthy1 sulfide hydrochloride 3 V Sthgcngw O-HCl This hydrochloride salt was synthesized by adding to a solution containing h g. (0.02h mole) of 3-thianaphthenethiol, 2.h g. (0.06 mole) of sodium hydroxide and 50 m1. of water a second solution prepared from 3.3 g. (0.018 mole) of @rqnorpholinoethyl chloride hydrochloride dis- solved in 25 ml. of water. The resulting reaction solution was kept at its reflux temperature for a three hour period at the end of which it was cooled and the product isolated by the procedure already described. The crude hydrochloride product was recrystallized from isopropyl alcohol after first treating its alcoholic solution with Norite, to give 2.1 3. (0.0066 mole, 37%) of a white solid which melted at 1h5-1h603. Calc‘d. for Cl4H160K82013 0, 53.23; H, 5.7h; 8, 20.30. Found: C, S3.h55 H, 5.7h; 8, 20.05. St: rub previouslj \ , w i.2 S L loin rd 5L). unreportei thianet A ‘43.. v c .‘l' .L ;_“11': 0511013 . .‘1 \(" (l) (2) (3) (1h) (15) (16) (17) (18) (19) (20) 92 BIBLIOGiAPHY M. H. Kim, H. D. Schuetz, J. Am. Chem. Soc., 72, 5102 (1952). W. H. Houff, R. D. Schuetz, J. Am. Chem. Soc., 15, 2072 (1953). R. A. Baldwin, 3. D. Schuetz, M. S. Thesis, Michigan State Univ., 1956. L. Gattermann, A. d. Lockhart, Ber., 26, 2808 (1693). K. Holler, Wien hed. wechenschr., 55, 1271 (188:). A. Einhorn, 3. 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