THE. SYNTHESIS OF SOME THSIRANES. blTHlfRANES, RELNEED M1-3NO~MERCAPYANS AND THEIR THIOACETATES Thesis {or the Dogs» of M. S. INCWGAN STATE uuwsasm Barf Jacob Bremmar £962. LYN THE ‘35 Kr ‘ 3 v THE SYNTHESIS OF SOME THIIRANES, DITHIIRANES, RELATED4AMINO-MERCAPTANS AND'THEIR THIOACETATES By Bart Jacob Bremmar A THESIS Submitted to the College of Science and Arts of Michigan State University of Agriculture and Applied Science in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department of Chemdstry 1962 DEDICATION To my wife Anita and our children Jackie and Randy, for their loss of my leisure time. 11 ACKNOWLEDGMENT Sincere appreciation for the aid and guidance given by Professor Robert.D. Schuetz during the course of this investigation is expressed by the author. He also is indebted to the management of The Dow Chemical Company who by their encouragement of the Graduate Ex- tension Program at Midland and by-their generous financial support during the residence period at lichigan State University, made possible the completion or this study. 111 VITA Bart Jacob Brenner gate and Place of Birth: September 4, 1930, in a nxveen, e etherlands. Education: Public School of Waddinxveen, The e erlands. Graduated from the "Christelijke MULO School”, 19%. "Christelijke Hogere Burger School" Alphen aan de Rijn, The Netherlands, 1946-1949. University of Leiden, The Netherlands, 1949-1950. Michigan State University, East Lansing, Michigan, Midland Extension, 1957-1961. In residence January-April 1961. Professional Positions: Inspection and Control Chemist, o , e on se Kearsenrabriek ”Gouda - Apollo", Gouda, The Netherlands, 1950-1951. (Dutch Army from 1951. Honorable discharge at the rank or 2nd Lieutenant in 1951‘.) Research Chemist, Grand Rapids Varnish Corporation, Grand Rapids, Michigan, 1953-1955. Chemist, Kelvinator Division or American Iotors Corporation, Grand Rapids, lichigan, 1955.195? . Research Chemist, The Dow Chemical Company, Hidland, Michigan, 1957-» Professional and Honor Societies: American Chemical oc e y ‘me Society of Sigma 11. 1V THE SYNTHESIS OF SOME THIIRANES, DITHIIRANES, RELATEDiAMINO-MERGAPTANS AND*THEIR THIOACETATES By Bart Jacob Bremmer AN'ABSTRACT Submitted to the college of Science and.Arts of Michigan State university of Agriculture and Applied Science in.partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department of Chemistry Year 1962 Approved ABSTRACT An objective of this investigation was to synthesize previously undescribed thiiranes and more specifically to develop synthetic methods for the preparation of dithiiranes. The starting materials used were the corresponding epoxides and diepcxides. The method used for the syns thesis of the majority of the thiiranes was similar to the procedure of Snyder, Stewart and Ziegler (1) modified in several cases. In this method, aqueous potassium.thio- cyanate is allowed to react with the corresponding epox- C ide to obtain the desired thiirane. 0 no \c/ \c/ secs 2 \/S\c/ soon / " \+ “fi/c' \+ The thiiranes synthesized by this procedure were, R‘O‘CHQ'T7m2 where R . allyl and p~tert butylphenyl. The dithiiranes were obtained from epoxys fre- quently used in the resin industry, namely diglycidyl ether of bisphenol A, resorcinol diglycidyl ether and hydroquinone diglycidyl ether. V1 /\/ fheir sulfur analogs appeared to be crystalline solids, which could be purified by crystallization from ethanol. An additional episulfide, l-methyl-l,2-epithio-h- isopropenylcyclohexane was prepared from the correspond- ing epoxide using the procedure of Bordwell and Anderson (2). Infrared spectra of the thiiranes and dithiiranes synthesized in this investigation were made, as well as of the epoxides from which they were prepared. A further objective of this study was to prepare amino-mercaptans from the thiiranes mentioned above. It was anticipated that such compounds would possess anti- radiation properties as drugs. Doherty, Burnett and Shapira (3) have reported that several compounds with the general structure, Hs(m12)nsnn have shown.promdsing antiradiation properties. The product resulting from the interaction of thi— iranes and secondary amines correspond closely to simple derivatives of this general structure where n.- 2: vii SH I /\ -_. ., .. , i ,_ _. g..." I R 0 CH2 CH CH2 + Heme—en o--CH2 CH (3&2me R - allyl, phenyl ERR; - morpholine, piperidine and diethylamine. The reactions were conducted in the presence of a nonionizing solvent such as benzene or ethyl ether using a.molar excess of amine over the thiirane. ln.most cases, the product was isolated as the hydrochloric acid salt. Finally, the thioacetates of the amino-mercaptans described were prepared.using a modification of the procedure of Glinton.8a1vador and.Laskowski (4) in which acetylchloride is allowed to react with the amino- thiol in benzene as a solvent followed by neutralization of the hydrochloric acid salt. .. - _ I .. -_, _ _, I ROCHzfliCIiaNR2+CH3OOCl——-)ROCI{2?HCliehIR2+HCl SH 3 I C n O I “”3 R.- allyl, phenyl ~Nflé - morpholino and.piperidino viii Where R u allyl, the compounds were isolated as the amine and.as the amine hydrochloride. Where R a phenyl, the compounds could not be distilled and were obtained only as their hydrochloric acid salts. Compounds of this type resemble the structure of acetyl choline, a drug having important physiological properties. These related sulfur compounds may there~ fore have properties resembling those of acetylcholine. References (l) H. R. Snyder, J. M; Stewart and J. B. Ziegler, J. Am. Chem. Soc... _6_9_, 2672 (19147). (2) F. G. Bordwell and H. ll. Anderson, J. Am. Chem. 30..., 15. l‘959 (1953). (3) D. G. Doherty, W. '1'. Burnett, Jr., and R. Shapira, Radiation.Research, 1, 13 (1957). (h) R. 0. Clinton, U. J. Salvador; 8. C. Laskowski, Jo mo Chews 300., L6.) 5152 (1953)! memo: CONTENTS Page mmowmos ..................................... HISTORICAL ....................................... The Preparation of 'J'hiiranes .................. Infrared Spectra of mum: ................. \D\OO\O\H Amino-Mercaptans - Derivatives of miiranes . . . Aminothioestors ..........~..................... 11 sxrssxnstAL ..................................... 13 Preparation of Allyl 2 ,3-Epithiopropyl Ether . . 13 Preparation of 2,3-Epithiopropyl Phanyl Euler Uscoco0000000000000assooooosIoI-oaoosoo 1h Distillation of p-Tert Butylphenyl Clycidyl Ether scascade-castes.assess-000000000009...o 15 Preparation of, p—Tert Butylphcnyl 2,3- Epithiopropyl mr .0...OCOQCOCOOOOQIOOOOOOC 16 Distillation of Grade assoroinol Diglycidyl Ether so0000000000000000000006...oocsosooooos 17 Preparation of n~Bis(2,3-Epithiopropoxy) amene .‘O-COOQOOOOOOOQOCOOOOIOOOOOOOOOOOOOCO 17 Preparation of Hydroquinono Diglycidyl Ether . . 19 Preparation of p~Bis(2,3«-Epithioprcpoxy) “Men. successscoo-sconcoct-sososooosseososo 20 Preparation of 2,2-Bis[p~(2,3-Epithio- propoxv)?honvl;7tropane ..................... 21 Preparation of 3-Chlorc«l,2-P oi (Glycerin: a-monochlorohydrin .............. 22 Preparation of Bis(2,3-Epoxypropyl)Ether ‘mglycidyl Ether) "DOO0.000COODOOOQOOC‘Q0.00. 23 Attempted Preparation of Bis(2,3-mithio~ propyl)Eth¢r cocoooscsoaeocsoosooosecs-sous.o 2“ x um 01' com -» Continued Page Preparation of l—Methyl-l,2-Epithio-l+—Iso— propenylcyclohexane (Limonene Monoepi- sulfide noose-osssoososossoocoooboe-coone."so 26 Attempted Preparation of 2, 3~Epithiopinene (Q‘Pinene Ep13U1f1de) 00.0000000000I09b0990I. 29 Preparation of o-Phenoxymethyl-ll—uorpholinc- ‘MthJ-Ol mmoria oaossasosscosossaoo 30 Preparation of eoPhenoxymothyloleipcridino- QWthiol HydrOChlorj-d. ssossaoaoooaocsooso 31 Preparation of c-(AllyloxyMcthyl-ll-Horpho» lineéthanethiol Hydrochloride . . . . . . . . . . . . . . . 32 Attempted Preparation of a-(AllyloxyMethyl-l- PiparidineethOI Hydrochloride a a a I s o c s a 33 Attenuated Preparation of l—Dialkylamino-B- Phenoxy-2-Propanethiol Salts ................ 33 Preparation of l-Diethylanino-B-Phenoxy-2~ PropmthIOI asses-cacaossssoasuooassesses... 3h Attempted Preparation of l~Allyloxy-3~ Diethylamino-2-Propanethiol . . . . . . . . . . . . . . . . . 35 Preparation of s-( l-Allyloxyme thyl-2~Morpho- limethy1)m1mc°tat. sosssaooosooooosooocsoo 36 Preparation or S-(l~Allyloxymethylr2—lbrpho- limethylrmioacetate Hydrochloride ......... 38 Preparation of S-( l-AllyloxymetMl—EJipcri- Mmthyl)?h10&ccht0 QIO¢¢I006D9000000900060 39 Preparation of S-(l-Allyloxymsthyl~2-Piperi- dinoethylrrhioacetate Hydrochloride . . . . . . . . . 140 Preparation of S-(2-Morpholino—l-Phenoxy- methylethyl)rhioacetato Hydrochloride ....... #1 Preparation of 8-( 2-Phenoxy-l-Piparidino- methylethyl)'l‘hioacetate Hydrochloride . . . . .v. . #2 Attempted preparation or 8- (2-Allyloxy-l- Die thylaminome thyl)ethyl ioacatate . . . . . . . 143 1 I TABLE OF CONTENTS - Continued Page ‘Infrared Spectra .............................. an DISCUSSION .u...uu.u.n.unnun...“..u... 63 'I'hiiranes and Dithiiranee .P....,.‘................ 63 Infrared Spectra of Oxiranea and Thiiranea . ._._. 72 Aminothioia otherivativea ot'miiranea ......_y.. 79 Aminothioacetatea ..’........_._.....,..........;... 80 aux-mums 83 xii Table II. II A. III. LIST‘OF TABLES Properties and.Analysis of Monoepi~ Sulfidas and Diepisulfides ............. Properties and Analysis of Amine Thiol Hydrochlorides DCOOOIOOQOOIOOOCOIOQOIOO. Properties and Analysis of 1-Diethy1— anino~3~Phenoxy-a-Propanethiol ......... Properties and Analysis ot.Amdne Thic- aeetates and.Anine Thioacetate Hydrochloridafl «assocnooaeooeo-ooooooooo Sons Infrared Absorption Bands at 0x11331198 m Mirama QOOOOO‘IOOQIIQOIOO xiii Page 45 ’47 78 INTRODUCTION The sulfur analogs of the alcohols (mercaptans), ethers (thioethers), esters (thioesters) and furans (thiophcnes) have received considerable attention and a wide variety or uses for some of them have been found. Such is not the ease with the sulfur analogs of the oxiranss or epoxides which are referred to as thiiranes or episulrides. The epoxides have found extensive applications as intermediates in the synthesis of alcohols, glycols and polyglycols. Since the commercial introduction or epi- chlorohydrin by the Shell Chemical Company, shortly after the Second World War, the production of epoxy resins has reached a substantial volume, predicted to reach 85~95 nillion.pounds by 1966 (13). Several collsrcial processes for epoxidation of olefinic compounds have further advanced epoxy resin technology and production (14,15). The success of the epoxies is not shared by the closely related episultides. While a higher than one oxirans functionality is of vital importance in epoxy resins, no thiirane with more than one thiirans group per molecule had been reported at the initiation or this study. The instability of many or the cpisulfides, difficulties in the experi— mental procedures available for their synthesis, and, nore important, the lack of any extensive utility are 1. 2. some of the reasons why this group of compounds has received limited attention. . Sons uses for episulfides and their derivatives have been reported, however. Alksnesulfides have found some industrial use in.the:ncdification of wool fibers (16,17) or to introduce sulfur into synthetic or polymeric materials where it is desirable to improve such properties as affinity for dyestuffs, resistance to water and organic solvents (18). Sons reaction products of ethylenesulfide with pri- mary and secondary amines (19) snd.ssrcsptans (20) are useful starting materials for the industrial preparation of dyes, textile aids, nedicanents and vulcanization accelerators. A Stanford Research Institute report (21) points out that episulfides per-it easy access to potenp tisl anticancer agents. as unique sugar episulfide was developed by this same Institute and was used in.an attempt to synthesise potential sntiradistion drugs (59:5°)~ Here recently it has been.found that certain thiirenes and.sose of their derivatives have sntituber. culosis activity (22,23,25,25,26). In one of these reports, (25) Aered and Brown, state that "Since the ssdority of episulphides are very active in vivo. it would appear that the episulphide structure is e neeeew ssry“sciety for antituberculsr activity.“ The report also sentions that—“The compounds with.en,episulphide 3. ring must. however, be comparatively simple in order to be active.” Some of the compounds that have been syn- thesized during the course or this inwestigetion.ney therefore very well possess entitubercular properties. The primary siniof this work, however, was to sync thesise some eminowmerceptans which.msy find utility as entiradistion drugs. It has been shown.(27,28,29) that one class of compounds which shows antirsdistion.proper- ties has the general structure R1 / Ra N—(a32)n-SH where u should be smaller than 3. Compounds with n.- 2 end those with branching in the slkyl moiety can be pre- pared by the reaction of thiirenes with secondary amines, several of which were prepared in the course of this inwestisation. The reaction products of dithiirsnes with secondary amines could result in.more active sntiradietion drugs, since they would contain the desired groupings at both ends or the molecules. Although none of these compounds have been.prepered es yet. the successful synthesis or several dithiirsnes, described in this study, opens up this possibility. Finally, the thioscetates or the emino~merceptsns, es \ . . . - . ‘. . . I .‘ ‘ u ' \ .‘ .. ’ ‘ s . ‘ ‘ l s . 1 - ~ ‘. ‘- ‘ ‘ \. ‘ ' \ ~- uv . O . \ l ’ ‘ e ‘1 ‘ ' . . v , s l . . \c \4 , n x. , . . . , ‘ ‘ . . \ o I V v - ‘ ‘ ' A, . . . . ‘ . ' I . w a . . , ‘ , . _ . l. . . ‘v . ‘ . . ' . . - x 4. - ~ . .‘ '-‘—1 ‘DI-n‘-_ . A‘ -A..- h. described above, were prepared. These compounds are structurally related to acetylcholine, a substance with a very powerful physiological activity, being many times more active than choline itself. ,By analogy, it was anticipated that the thioacetates would be more active as antiradiation drugs, or would have certain physio~ logical properties similar to acetylcholine, such as a depressant of blood pressure, or as an agent causing muscle contraction. The terminology associated with the cyclic three membered sulfides parallels the nomenclature for the cyclic three membered others. The names thiirane, episulfide, alkenesulfide or epithio of the sulfur comp pounds, correspond to oxirane, epoxide, alkeneoxide and epoxy of the cyclic others. A few alicyclic sulfides are described as thiacycloalkanes. The nomenclature used for cyclic sulfides by Chemdcal Abstracts, in most cases, amounts to replacing the term epoxy in the corresponding cyclic other by the term epithio. For example, the compound 0 / \ cue-cs-miz-o—csa—cs-mia is named allyl 2,3-epoxypropyl other, while the corres- ponding 5. S / \ Chg-«(1H«Che-~-oatmaa-CH-dm2 is referred to as allyl 2,3-epithiopropyl other. Excep- tions to this rule are found in certain bieyclic com-- pounds where one ring has the episulfide structure. In such case, the term thiabicyelc or thiaspiro- is used. For instance, an s / 2\/\ fine We CH CH a / 2 C112 is referred to as l-thiaspirefa.5Joctane. In the present study, the nomenclature employed is that of Chemical Abstracts when dealing with new or less familiar compounds. This includes all of the cyclic sulfides, their derivatives and certain of the cyclic others. A few of the epoxides, however, are better known by name not in use by Chemical Abstracts. Such names will be used occasionally, where it adds to the clarity of the text. For example, the Chemical Abstracts name n—bis(2,3-epoxypr0poxy)bensens is replaced by the more familiar resorcinol diglycidylether. HISTORICAL The Preparation of Thiiranea An excellent review or the literature covering the synthesis or episulfides was prepared by Jacobs (2) in 1959. Since then, little has been.publiahed in this field, with the exception of the work by Doyle and his co-workers (23). These investigators, in a search for antituberculous drugs, synthesized some new thiiranes using the method or Harding. Owen and.nules (30,31), consisting of the alkaline hydrolysis of ecctylated, propylated and butyrated hydroxythicls. The method was successful in.the case or the acetates and moderately successful with the propionates. Adams and oo-workers (2h) made several substituted propyleneeulrides from.the corresponding oxides and thiourea. Although Jacobs has reported the history or the thiiranes in detail (2), some or the highlights deserve attention here to provide preper origination to the work reported here. The parent thiirane, ethylene- sulfide was made relatively late in the development of the thiiranss. In 1920, Delepine (32,33) allowed an aqueous solution of sodiun.sultide to react with ethylene chlorothiocyanate (made from symmetrical 7. diohlorosthylsns and potassiun.thiocyanats) to obtain sthylonssultidc in low yield. CHQCI-Cliacl + xscs—acnem-cnescn CH Cl-CH SCN + Na S-——~—)CH ~CH + NaCl + NaSCN 2 2 2 21/ 2 S Later Dolspins and Eschsnbrsnnsr (3h) found that the yield of sthylenssulrido is considerably improved when using ethylene dithiocyanato as the starting material. This method has since bosn.utilizod by Mousssron (35) to prepare l-thiaspirqzré.5;7botans, 1,1-56H10-0Hé5. Daohlauer and Jacksl (36) havs introduced the use of aqueous thioursa to synthesis. alksnssulridss from.ths corresponding spoxides. S O CHE/FH2'+ HeN-C-NH2-———-—) \E;?HQ + HeN-C [-NH2 This method was later extended by Culvanor, Davies and Pausaoksr (9) and more recently improved by Bordusll and Anderson (10). The latter investigators showed that in the formation or prepylonssulridc fromjpropylsnsoxida a considerable reduction in the amount of polymeric 8. materials resulted by increasing the acidity of the reaction mixture. The yield of prepylenesuli‘ide was in- creased by 20%, for example, by adding 2.5 mole per cent or acid (hydrochloric, sulfuric, acetic, perchloric, benzoic, p-toluenesulfonic) to the aqueous solution of thiourea. An equimolar quantity or acid yielded a 50% increase or the episultide. A 5-hydrcxythiouroniun.salt is formed when an.cquivalent amount of an acid is used in the reaction between an alkenecxide and thiourea. This salt may be made to yield the alkenesulrides on alkaline hydrolysis. Dachlauer and Jackal (37) also described the use of potassium.thiocyanate in an aqueous solution at room temperature to transform epoxides into episulrides. .0 ' \ H20 / ‘ cue-cs2 + Keen—acne-cne + KOCN This general procedure has been.extended by Snyder, Stewart and Ziegler (l) and also by Price and Kirk (38). The reaction is general and remains one of the most con- venient laboratory procedures for the synthesis of cyclic sulfides. This process or modifications thereof was used in the majority of the reactions in which thiiranes were synthesized during the present investiga- tion. 9. Infrared Spectra of Thiiranes The initial work on the infrared spectrum.of cthylcnesulfide was that of Thompson and.Dupre (39). Guthrie, Scott and Waddington (40) observed, however, that certain of the bonds reported by Thompson and Dupre (39) were due to traces of polymerized sulfide and/or other impurities. At about the same time, Thompson and Cave (hl) reinvestigated the infrared spectrum.confirm~ ing the observations of Guthrie and eo-uorkers (no). Recently, Moore and Porter (42) reported the princi- pal bands observed in the infrared spectrum of 1,2- epithio-octane. Amino-Mercaptans - Derivatives of Thiiranes Ring cleavage of thiiranes by primary and secondary amines have been described by Reppe and Nicolai (43). They conducted the cleavage.reaction.et 100-200'0. in the presence of s substance capable of lowering the pH of the reaction, such as phenol. Snyder, Stewart and Ziegler (1) carried out the reaction of several alkene- sulfides with a variety of primary and secondary amines at or near lOO'C. for reaction periods of 10 to 20 hours in the absence of a solvent or catalyst. They observed no beneficial effect when either phenol or aluminum chloride was added. Only "normal” ring fission was observed by Snyder and his associates. In all instances, 10. more or less of the initially formed aminothiol reacted further to form.polymeric material. The use of excess amine depressed thispolymer formation reaction. Bras (as) demonstrated that the severe reaction.conditions previously employed (R3) were not necessary and fre- quently were undesirable, since they favor side reactions. He also observed that when freshly prepared ethylene- sulfide was added to a solution of the amine in an ionizing solvent, and this was set aside at room.tem~ perature for a few hours, almost complete conversion of the sulfide to polymeric material occurred. On the other hand, when a nonionizing solvent was employed, such as ethyl ether or benzene, polymerisation of the sulfide was almost completely suppressed and the amount of aminothiol substantially increased. This procedure was used by Sohmolka and Spoerri (#5) and more recently by Jacobs and Schuetz (61), who observed similar results as those reported by Bras (4h), namely, utilization of a nonionizing solvent and molar excess of amdne tend to increase the yield of the amino-mercaptan. The reaction of diethyl amine and alkyl 2,3oepith10propyl others was reported (61) to be erratic. Instead of isolating the amino~mercaptan, the final distillation resulted in the recovery of the starting materials in almost quantita- tive amounts. Jacobs and Sohuetz suggested that these amino~mercaptans readily split out diethyl amine. ll. Andnothioesters Clinton, Salvador and Laskowski (lbw and previous references cited) of the Sterling-Winthrop Research Institute have synthesised a considerable number of aminothioesters. These compounds were reported to possess activity as local anesthetics. Their general structure can be represented as 0 Ar» '3-(Cfle)anRQ where.Ar is an.arometic or substituted aromatic nucleus and n is 2, 3 or R. Similar work was reported by thraala and Ho Elvain.(h7) and Liecher and Jordan (#8) who prepared a series of 3-dialkylsninopropyl h-amino« thiolbensoate hydrochlorides vie 3-chloropropyl i-nitrothiolbensoate. Hansen.and,rosdick (49) prepared the thio analog of novacaine or procaine which is called thiocaine using a substituted thiolbensoete as an intermediate. The thiocaine, p-NH2C6HQWSQ12CHQN ( C235) 2 was found to have more anesthetic efficiency, but was more toxic than.the related novacaine (50). In.all oases mentioned, the sulfur in these aminothioesters 12. was introduced by means of a thiol acid (47,48,h9) or from a dialkylaminoalkanethiol, HS(CH2)nNR2 (4). In none of the cases reported were there any substituents on the polymethylene chain of the general formula 0 n Ar-C-S-(CH2)nNR2 Such a structural change could be obtained (with n - 2) by the reaction of dialkyl amine with thiiranes, (other than ethylenesulfide) followed by the reaction of the product with an.acid chloride. EXPERIMENTIL Preparation of Allyl 2,3-Epithiopropy1 Ether 032.63-0112‘0-CH2‘CH”CH2 \s/ The thiirane was prepared from the corresponding oxirane and aqueous potassium.thiocyanate, utilizing the procedure of Snyder, Stewart and Ziegler (1). In a 500 ml. three-necked flask fitted with a sealed stirrer, dropping funnel and reflux condenser, were placed 97 g. (1.0 mole) of potassium.thiocyanate and 100 ml. of water. To this vigorously stirred solution was added dropwise iiu g. (1.0 mole) of allyl glycidyl ether (used as obtained from the Shell Chemical Co.) during an hour and three quarters. fhe turbid solution was stirred for an additional three hours and set aside overnight. The two-phase systen.was separated and the organic phase was treated as described above with a fresh aqueous solution of potassium thiocyanate (50 g. of the salt in 100 ml. of water) for six hours. who two-phase system.was again separated and the aqueous layer was combined with the first aqueous phase and extracted with three 25 ml. portions of ether. The camp bined ether extracts and organic phase were dried over anhydrous sodium sulfate and the ether removed. The 13. in. crude product was distilled under vacuum through a 23 x 1.8 cm. column.packed with 1/8 inch glass helices. The major fraction distilled at 46-48'0. (h mm.)3 n§§ l.h913. A yield of 63.5fl'was obtained. Elemental analysis for c6H1003 gave the following results. calculated: 0. 55.35; H, 7.74; 8, 2&.62. Found: C. 55.53; H. 7.821 8, 24.58. Preparation of 2,3-Epithiopropyl Phenyl Ether 06H5-0-m2-G{17CH2 3 A 150 g. (1.0 mole) quantity of phenyl glycidyl ether (used as obtained from the Shell Chemical Co.) was added in a single portion to a solution prepared from.2h2 g. (2.5 moles) of potassium thiocyanate dissolved in 200 m1. of water and 150 ml. of ethanol and contained in a l-L. three-necked flask equipped with a mechanical stirrer, reflux condenser and thermo- meter. After the reaction mixture was set aside over~ night, an additional 150 g. (1.0 mole) of phenyl glycidyl ether was added to the reaction.mixture and it was stirred vigorously for thirty-six hours. The supernatant layer and the aqueous phase were decanted from.the precipitated potassium cyanate into a l—L. separatory funnel. The potassium.cyanate was rinsed 15. with two 50 m1. portions of other, and these were trans- ferred to the separatory funnel and used to extract the 2,3-epithiopropyl phenyl ether. me ether extract was washed twice with 100 ml. portions of saturated sodium chloride solution and dried over anhydrous sodium sulfate. me ether was removed in vacuo and the liquid product distilled under reduced pressure through a 50 cm. Vigreux column. The main traction distilled at 106'0. (0.9-1.1 man): his 1.5738. the yield of the product was 57.3%. (Physical constants reported by Jacobs (2) for 2 ,3-epithiopr0pyl phenyl other: b.p. 106.0.(1 m.): 11%5 1.5735. Distillation of pv'i‘ert Butylphenyl Olycidyl Ether p-tort Butylphenyl glycidyl other obtained from the Dow wemical company as a special sample was dis- tilled under reduced pressure through a 50 cm. Vigrcux column. The main portion distilled betwaen 98-100'0. (0.2 men): n35 1.5129. Epoxy equivalent weight calcu« lated: 206; Pound: 208.5. Slagh and Alquist (5) describe this material as a colorless mobile liquid boiling at 145.152'0. at 0.2 inch pressure. - 16. Preparation of p—lertJButylphcnyl 2,3-Epithiopropy1 Ether - s3coc- «wane-0570112 lhe experimental procedure employed in the synthesis of this material was the same as that used to prepare 2,3-epithiopropyl phenyl other with the exception that a volume of acetone, equal to the volume or water used, was added to the initial charge of reactants to insure a homogcnous reaction.mdxture. After two separate distillations or the crude product, there was obtained, in small yield’, a colorless liquid, which distilled at 119%. (0.25 ml); n35 1.5443. Elemental analysis for 01331303. Calculated: c, 69.68; H, 7.9“; 8, lh.22. Pound: c. 70.22: H, 8.163 8, lfl.fl2. *The yields of some or the reactions are not indicated. these are the reactions that required many crystallisa~ tions or repeated distillations for purification. Ehesa yields are therefore low. Since these reactions were only run once or twice, good conditions were not found and considerably higher yields can be expected in subsequent trials. Inc yields as obtained are therefore close to meaningless. 17. Distillation of crude Resorcinol Diglycidyl Ether Resorcinol diglycidyl ether, supplied by the Keppers Chemdcal Company under the trade name Kopoxite 159, was distilled in vacuo through a 20 cm.‘Vigreux column. The main fraction distilled at 177-188'0. (1.4 mm.) (the wide boiling range is due to a mixture or diastereoisomers); nfi? 1.53893 nfi? 1.5h08. Epoxy equivalent weight calculated: 111.1: Found: 11h. Physical constants reported by Verner and Farenhorst (3) for resorcinol diglycidyl ether: b.p. 210-220‘0. (12 mm.); n3? 1.5408. ' Preparation of menis(2,3-Epithiopropoxy)Benzene . -0~cse-cni-e12 (mam-cage- \/ ‘ s A 500 ml. flask equipped with a stirrer, thermo- meter and reflux condenser was charged with 121 g. of potassium.thiocyanate (1.25 moles), 100 ml. of water, 75 m1. of ethanol and ST 3. (0.5 equivalent) of resorcinol diglycidyl ether and the mixture was set aside overnight. The initially clear reaction.mixture became turbid in about one hour and the following day a white solid had precipitated from.the solution. The 18. mixture was then stirred for twelve hours and the precipitate was removed by filtration and extracted with 300 ml. of benzene. The benzene extraction was repeated a second time with 100 m1. of benzene. The benzene extracts were combined and dried over anhydrous sodium sulfate. the major portion or the benzene was removed by evaporation in vacuo causing a white pre- cipitate to form. The latter was recovered by filtra- tion and weighed 15.1} 3. after drying. From the mother liquor an additional 39.5 g. of the white solid was obtained by evaporation of the benzene. Part or the initial crystalline material was recrystallized four times from absolute ethanol to obtain a white crystal- line mterial which melted at lll.5-ll3.5‘0. Elemental analysis for 012311.028... gave the following results. calculated: c, 56.66: B, 5.55: 8, 25.21. Found: 9. 56.48; H. 5-42: 8, 25.07. 19 . Preparation of Hydroquinone Diglycidyl Ether Warm-w‘ry'o- vo-CHQ-CH-ffig \ O O A two liter flack was equipped with a stirrer, thermometer, water separator, condenser and nitrogen gas inlet tube. In the flask were placed 165 g. (1.5 moles) of hydroquinone and 1387.5 3. (15 moles) of epichloro~ hydrin. rm stirred mixture was heatedto wire. and 219.6 g. (3.12 moles) of 50! non solution was'added to it. the reaction tenperature was maintained at mm. by steam distilling water and epichlorohydrin from the reaction mixture. me epichlorohydrin was separated fro- the steam distillate and returned to the reaction vessel. he addition of the sodium hydroxide required two hours and forty airmtes. mien all the base had been added. the excess epichlorohydrin was removed by distillation to a pot temeraturs or 150%. (30 m.) and replaced by an equal voluae of toluene. The insoluble salt toned during the reaction was removed by filtration and the toluene was removed under reduced pressure. he crude product was distilled under vacuum through a 20 ea.Vigreua column. Ehe major portion boiled at tilt-183%. (0.5 u.) (the wide boiling point range is due to diastereoisomers) . 20. A 55.4,»yield was obtained. Epoxy equivalent weight calculated: 111.13 Pound: 113.5; m.p. 90-101'0. Physical constants reported by Herner and Fahrenhorst (3) for hydroquinone diglycidyl ether: b.p. approxi- mately 155’0. (0.03 mm); m.p. one isomer 89.5-90.5'0.; other isomer 118-119'0.‘ ‘ ' Preparation of p-Bis(2,3-Epithiopropoxy)Benzene CHa-fL-CHZ-O- ~0-032-CH- 2 \3 \f' A 500 ml. three-necked flask equipped with a sealed stirrer, thermometer and reflux condenser was charged with 25.5 g. (0.26 mole) or potassium thio- cyanate, 20 m1. of water and a warm solution of 15 g. (0.13 equivalent) of hydroquinone diglycidyl ether dissolved in 75 ml. of acetone. The reaction mixture was heated to 50'0. and kept at this temperature for 30 minutes and was then set aside overnight. Il'he following day the crystalline solid which had formed was recovered by filtration and extracted with 150 ml. of carbon tetrachloride. Qhe carbon tetrachloride extract was dried over anhydrous sodium.sultate and the solvent was removed in vacuo. me crude product thus obtained was recrystallized six times from ethanol 21. to obtain a white crystalline material; m.p. 134.5— 136. 5‘0. Elemental analysis for 0128140282. Calculated: c, 56.66; a, 5.55; e, 25.21. round: c, 56.65; H. 5.80: 3. 25.12. Preparation of 2,2 -sia[p-(2,3-spithiopropoxy)rnerwi_7 Propane CHB Cl\i:-CH-CH2-O~ Q: ~C- GHQ -O-CHQ-CH \s-fflz In a 500 ml. three-necked flask fitted with a sealed stirrer, reflux condenser and thermometer, were placed 121 g. (1.25 moles) of potassium thiocyanate, 75 ml. of water, 130 ml. or acetone and 88 g. (0.5 equivalent) of distilled diglycidyl ether of bisphenol A (obtained from he Dow Chemical company as DEB 332 L0). The reaction mixture was stirred vigorously for three and a half hours during which a mass or white crystal-s line material formed in the initially clear solution. line reaction mixture was heated to 60‘s. for three hours and an aliquot was taken from which the crystals were recovered by filtration, ushed with water and recrystallised from ethanol. he melting point or this material use 88-91'0. fhis procedure was again repeated after an additional reaction period of four 22. hours at 60'C. The melting point or the product here was 91-93‘0: Following a third reaction period of four hours at 60’0” all the crystalline material formed during the reaction was filtered out, washed with water and recrystallized from ethanol to obtain 9. 35¢ yield of a white crystalline material melting at 93-95'0. Elemental analysis for caseuoesz gave the following results. Calculated: c, 67.71: H, 6.149; 8, 17.21. Found: c, 67.70: H, 6.#53 3, 17.38. Preparation of 3-Chloro-1,2-Pr0panediol (Glycerine a-monochlorohydrin) eagerness-macs In a one liter three—necked flask equipped with a sealed stirrer, thermometer and reflux condenser were placed 277.5 g. (3 noise) or eomrcial epiehlorohydrin, 5110 a. (30 moles) of water and 0.55 a. or concentrated sulfuric acid. The stirred reaction mixture was kept at a tamer-attire or 75-85‘0. for three hours, cooled to room temperature and nontralized (pH at 7) with 25% aqueous sodium hydroxide. Excess water was then removed from the reaction mixture and the crude product was distilled under reduced pressure through a 50 cm. Vigreux column. The main portion distilled between 23. 98 and 99'6. (3.h mm.). A yield of 79.5% was obtained; his l.fl796; n;?'5 l.u813. Physical constants reported by Boesekens and Hermans (6) for glycerine c-mono- omomarinj'bepo 116.0. (11 m.)3 "$7.5 1048200 Preparation or.Bis(2,3-8poaypropyl)£ther (Ddglycidyl Ether) 63:7“-m2-°.w2-ci7m2 The procedure followed was that described by Dudley (7). A two liter three-necked flask equipped with a stirrer, thermometer, condenser and drapping tunnel was charged with 223 g. (2.2 moles) of 3~chloro- 1,2-propanediol and 5.1 g. concentrated sulfuric acid. The mixture was heated to 95‘0. and 185 g. (2.0 moles) or epichlorohydrin added during two and one half hours. After adding the epichlorohydrin, the reaction.mixture was kept at 95' for three hours, cooled and set aside overnight. Benzene, 176 g.. was then added and the solution was chilled to below 0‘ in an ice-salt bath. next, a solution containing 193’s. (h.83 moles) of sodium.hydroxide dissolved in 285 g. of water was added during an hour and three quarters, while holding the reaction temperature below 5’0. Following p all. neutralization, the mixture was stirred for a half hour and filtered to remove the sodium chloride. The ben- zene layer was separated and the aqueous layer extracted with .188. g. of benzene. The benzene extracts were combined with the initial layer and after removing the benzene by distillation under reduced pressure, a 55% yield of the crude bis(2,3-epoxypropyl)ether was ob- tained. Vacuum redistillation of the ether through a 50 cm. Vigreua column gave an 18$ yield of the pure product, boiling at 96-97'0. (9 1mm); n35 1.4458. Epoxy equivalent weight calculated: 653 Pound: 65.9. ms boiling point for bis(2,3~epoxypropyl)ether is reported by mdley (7) as 96-97‘0. (9 man). Its re- fractive index at 25‘s.. as reported by Roach and wittcotr (8), in 1.41155. Attempted Preparation of 315(2, 3-»Epithioprcpyl)3ther Gl\‘-I:7Q-CHZ-O-Cfiz-C{:/CH2 A 500 ml. three-necked flask equipped with a stirrer, thermometer, dropping funnel and a condenser was charged with 61 g. (0.63 mole) of potassium thie- cyanate and 50 ml. of water. A 33 3. quantity (0.5 equivalent) of bis(2, 3—epozypropyl)ether was added drOpwise during 50 minutes. 'l‘he exothermic reaction 25. was kept below 32.0. by external cooling. Following the addition or the epoxy other, the reaction mixture was stirred for an hour and fifty minutes, 60 ml. of benzene 1aas added and the mixture was stirred an additional forty-five minutes. The benzene layer was separated from the aqueous layer and the latter ex- tracted three times with 25 ml. portions of ether. the other extracts and benzene layer were combined, washed three times with 50 ml. portions of distilled water and dried over anhydrous sodium sulfate. me ether and benzene were removed in vacuo. The product was dis- tilled under reduced pressure through a short path distilling apparatus. One fraction distilled at 82~ 83'0. (0.25 mun); n35 1.5498. Elemental analysis of this material for 06810082 gave the following results. Calculated: a, 41mm 11, 6.213 3. 39.52. Found: 0, “1.893 B, 6.37; 8, 37.39. he second traction dis- tilled at 83-85'0. (0.2 mm.” n§5 1.5508. Elemental analysis, Found; 0, (£5.17; 3, 6.39: 3, #030. 26. Preparation of l~lbthyl-l,2-Epithio-h~1sopropenylcyclo- hexane (Limonene Ionoepisulfide) m3 3 c /\ (313% The product was prepared from the corresponding oxide, limonene monoxide, obtained from.the Food Ihchinsry and chemical Corporation. Several experiu mental procedures were examined. the epoxide was used as received and had the following physical properties: epoxy equivalent weight calculated: 152; Found: 159.9; ngé l.#6513 hi? l.#672. Literature values mg? l.h697 (11). 3;... WiedjmeQum of Snider. seem 95.3 Ziegler {1); In a 500 ml. three-necked flask equipped with a stirrer, thermometer and condenser was placed 135 E. (1.h moles) of potassium.thiocyanatc, 100 ml. or water, 75 ml. or ethanol and 80 g. (0.5 equivalent) or lw methyl-l,2-epoxy~h-isqprepenylcyolohexana (limonene monoxide). The heterogenous two-layer reaction was stirred vigorously for 16 hours. IAn aliquot of the 27 . organic phase or the reaction mixture was taken and, on removal of the solvent only, starting material was obtained. 'Ihc reaction was then refluxed for fifteen hours, cooled, transferred to a separatory funnel and the uater layer remved. The salt which had formed during the reaction was rinsed twice with 50 ml. portions of ether. Ithe other extracts were combined with the organic layer, which was washed twice with, 50 ml. portions or a saturated sodium chloride solu- tion and dried over anhydrous sodium sulfate. me solvents were removed in vacuo, and the product dis- tilled in vacuum through a 50 cm. Vigreux column. A yield of 37 .9 2’. consisting minly of starting material use obtained. a second attempt to prepare this thi- iranc using this method by replacing the ethanol with acetone gave similar results. _‘1310 method; of culvenor. Dam and Pausecker 12. ) 3 Into the apparatus described above, with the aid or a (trapping tunnel. no placed 42 3. (0.55 mole) of thiourea and mo :1. or methyl alcohol. mo stirred mixture was cooled to 1-2‘c. and held there while 80 g. (0.5 equivalent) of lunethylul.2-epoxy-haisopropenyl- cycloheacane sac added dropsise to it, during an hour. he reaction mixture was allowed to warn to room temperature, stirred an additional four hours, then poured into 300 ml. of water and extracted with three 7 5 ml. portions or napentane. I.Ifhe combined extracts 28. were dried over anhydrous sodium sulfate and the n—pentano was removed in vacuo. Epoxide was recovered in a 95.5% yield. ghe method of Bordwellfld finder-son 410); In the same apparatus were placed 175 ml. of water, 13.5 ml. (0.5 equivalent) of sulfuric acid and 38 g. (0.5 mole) of thiourea. The contents were cooled to (re. and held between o-s‘c. while 80 g. (0.5 equivalent) oi1 l-methyl-l,2-epoxy~lt—i;0propenylcyclohexane was added dropwise during two hours. The reaction flask was kept imersed in the ice-bath for an additional twenty minutes. External cooling was removed and the reaction mixture was allowed to warm to room temperature in three hours. An aqueous sodium carbonate solution‘ (53 5.. 0.5 mole in 250 ml. of water) was added to the acidic reaction mixture during a half hour. Two layers formed. the upper organic m a resin-like white material. his was separated from the aqueous layer and extracted with four 50 m1. portions of n-pentane. Only a small part or this material was soluble in n-pentane. ‘lhe hydrocarbon extract was dried over anhydrous sodium sulfate and the n-pentane removed in vacuo. the crude material was distilled under reduced pressure through a short path distilling apparatus. he 1-methyl-l,2-cpithioall-is0propeny1- cyclohexans distilled at 63-65’0. (3 mm); 11?? 1.5152 and Iran obtained in a 9.6% yield. (Elemental analysis 29. for 91cfl163 gave the following results. Calculated: c. 71.36; H. 9.58; 3, 19.05. Found: c, 71.38; 3. 9-393 3. 19.06. Attempted Preparation of 2,3-Epithiopinene (a-Pinene Episulfide) the synthesis or this optically active thiirane was attempted starting with a—pinene oxide (Food Machinery and Chemical Corporation). The epoxide was used as received and had a n:? or l.h672; mg? 1.4692. Literature values n3? 1.4697 (12). inc usual methods for the determination of epoxy equivalent are not applicable to a~pinene oxide (12). lhree procedures were tried in the attempt to make this thiirans. The procedure of anyder, Stewart and Ziegler (l) as well as that of Culvenor, Davis and Pausacksr (9) resulted in the recovery or the epoxide _ starting material. The method of Bordwell and Anderson (10) as described under the preparation of 30. lnmethylol,2-epithievhoisopropenylcyclohexane gave mostly polymeric material . Preparation of c-Phenoxymethylelt-florpholine'e'thanethiol Hydrochloride /Qi2-CH2\ -o.cna..('m-caa-x /O.HCl . es sag-(>152 A 125 ll. filter flask. was charged with 8.7 g. (0.1 mole) of aorpholihe and 7.5 ml. of benzene. Il'he mine solution was cooled to 0%. and a prechilled solution or 8.3 a. (0.05 molefoi‘ 2,3—epithiopropyl phenyl enter dissolved in 7.5 ll. of, benzene was. added portionsise during a ten minute period. 'i'he reaction mixture was held at o’c. for an additional hour and then warned to room tomenture. Subsequently, the filter flask ass equipped rith a condenser and its side arl closed off. file reaction mixture was then heated for one hour at its reflux taperature. he excess norphcline and benzene were rnoved in vacuo. he residue was dissolved in about 25 ml. or dry ether and dry hydrogen chloride was was bubbled into the solution. the shite precipitate which formed was recrystallised three times from a aixture (1:1) or isopropyl alcohol and methanol. the a-phenoxymethyl-4~ 31. morpholineethanethiol hydrochloride, melting at 166- 1663‘s., was obtained in a 55.5fl yield. Elemental analysis for 6131119N028oHCl gave the following results. Calculated: c, 53.87; H, 6.96; 3, 11.06: N, 18.83;. 61, 12.23. round: 0, 53.91; H, 6.893 3, 11.014; :4, “.72; (:1, 12.26. Preparation of a-Phenoxymethyl-luPiperidine’éthanethiol Hydrochloride /¢32"Cfi2 -0-CH2-m—Cngl /cH2 -HCl I 33 \wz-cfie lhis compound was prepared frca piperidine and 2.3-epithiopropyl phenyl ether utilising the procedure previously described for the synthesis of e-phencxy-o nethle-lorpholinee'thanethicl hydrochloride. lhe e~phemynethyl~l~piperidineithanethiol hydrochloride ass obtained after three recrystallisaticns from iseprepyl alcohol in a 35.0’ yield and melted at isms-1211.90. Elemental analysis for clauses-sci save the folloaing results. calculated: c. 58.41; s. 7.70; s, 11.1% s, 4.86. oz. 12.32. Found: c. 58.56.11, 7.51; s, 11.3!» s. b.79: c1, 12.62. 32. treparation of e-(Allyloxy)llethyl-lt-florpholineethenc- thiol Hydrochloride /CI-12-C32 wz-w-cna-o-cae-fs-cuem 04401 A 125 ii. filter flask was charged with 8.7 g. (0.1 mole) of nomholine and 7.5 ml. of anhydrous ether. the solution was cooled to 0'6. and a prechilled solu- tion or 6.5 g. (0.05 mole) oi: allyl 2,3-epithiopropy1 ether dissolved in 7.5 ml. of anhydrous ether was added portionwise during ten minutes. Ime reaction mixture was held at 0‘0. for an additional hour and then warned to room temperature. he filter flask was then equipped with a condenser and its side arm closed off. he reaction mixture was heated for an hour at its reflux temperature. the excess norpholine and ether were removed in vacuo and the residue was dis- solved in about 25 m1. of anhydrous ether. Dry- hydrogen chloride use passed into the ether solution, precipitating a white solid. his was recrystallized four times from a mixture (1:1) or isoprOpyl alcohol and other. ‘me pure hydroscopic compound was obtained in. a 55.2! yield and melted at 79.8-—81.8'C. Elemental analysis for 610H19m28~flcl gave the follow- ' ins results. Calculated: 0, 47.31, H, 7.91}; 33. 3, 12.63; s, 5.5a, c1, 13.97. Found: c. 47.04: H, 7.903 8, 12.48; N, 5.22; Cl. 13.68. Attempted.Prepsration of a-(Allyloxy)lethyl-l-Piperi- dineethsnethiol Hydrochloride cue-cue GHQ-Qi-CHQ-O-CHQJ‘H'I-CHQ-N \ . CH2 OHC]. SH CHE-C112 Piperidine and allyl 2,3-epithicpropyl ether were allowed to interact in the manner described for the preparation of or(sllylonymmthyl-h-morpholineéthence thiol hydrochloride. The up(allyloxy)methyl-l~piperi~ dineéthanethiol hydrochloride could n.. be obtained in the pure form.due to its very hydroscopic nature. Attempted treparation or l-Ddalkylanino-3-Phenoxy-2~ Propanethiol Salts {a I -o-csa-os-cs -nwux i2; Diethylsnine and.2,3~epithiqpropyl phenyl other were allowed to interact as previously described under the preparation or a~(allyloxy)asthyl-u-morpholinee Ethanethiol. The salts of the tollosing acids were 34. prepared: hydrochloride acid, p-toluene sulfonic acid, naphthalene sulfcnic acid, sulfuric acid, picric acid, phosphoric acid.. However, none of these salts could be obtained in a good crystalline form, making'further purification impossible. Similar results were ob- tained with the salts of the reaction product obtained by the interaction of di-n-butylamine and 2,3-epithio- propyl phenyl ether. . Preparation of 1~Ddethylamino-B-Phenoxy-aoPropanethiol CH2~CH3 -°-CH2-fH-m2-N< SH One-G33 Jacobs and Schueta (61) have shown that compounds of this type will readily decompose to the materials fron.ahich they are easily prepared, namely, the dialkylamine and thiirane. Because the salts of the acids most likely to be crystalline compounds turned out to be oil-like materials, making their further purification impossible, it was decided to prepare the l-diethylsadno-a-phenoxy-a-propanethiol fron.very pure starting materials and thus obtain the pure compound. Carefully purified 2,3-epithiopropyl phenyl ether was allowed to react with freshly redistilled diethylamine in the manner described under the preparation of 35. e-(allylosy)nethy1~_lb—morpholine'ethanethiol. The pro- duct was obtained in a quantitative yield, n35 1.5280. Titration with 0.1-1! 3280;; indicated an amine equiva- lent weight 01' 21114.3. Calculated 239.5. Elemental analysis for 0133211608, calculated: 0, 65.20; 8, 8.84; II, 5.88; 8, 13.39. Found: c, 65.17! K: 8.71; N. 5.56; 8. 13.26. ~ Attempted Preparation of l-Allylocty-S-Diethylamino-z- Propanethiol /‘m‘*""’“~3 Gig-Givfliz-Occfla-Gfiufiia-N e was}, Freshly redistilleddiethylalins was allowed to react with very pure allylozd-epithiopropyl ether following the experimental procedure described under the preparation or lcdiethylanino-s-phenoxy-z- propanethicl. me yield, in this case, was only 90.6} or the theoretical yield, n35 1.1t780. Titration lith 0.1-4! 32301, indicated'an nine equivalent weight or 215.0. calculated 203.5. Eleaental analysis for closures. calculated: 6, 59.0“; H, 10.31; H, 6.93; I, 15.76. found: 0, 59.13; 3, 10.913 N. 5.95! e, 16.92. 36. Preparation of 8-(l-Allyloxymethyl~2-flbrpholinoethyl) Thioacetate GHQ-CH-cfia-O-GHQ-ffi-Gflz-N ’//O ? CHE-632 0—0 I ““3 In a 500 ml. three-necked flask equipped with a stirrer, reflux condenser and dropping funnel was placed 133.8 g. (1.54 moles) of morpholine dissolved in 100 ml. of benzene. The solution was cooled to 0'6. A prechilled mixture of 100 g. (0.77 mole) of allyl 2,3-epithiopropyl ether dissolved in 90 ll. of benzene was added during 10 minutes. the reaction mixture was kept at 0‘6. for an additional hour and then warmed to room temperature, followed by heating at its reflux temperature.for an hour. the benzene and.excess morpholine were removed in vacuo. The intermediate crude eephenoxymethyl~uamorpholineethane- thiol was obtained in 903$ yield. the corresponding thioacetate was synthesised following a slightly modified procedure described by Clinton, Salvador- and Laskowski (u). A solution of 31.0 g. (0.383 mole) of acetyl chloride dissolved in 125 ml. of benzene was placed in.a 500 m1. three-necked 37. flask equipped with a stirrer, condenser and dropping funnel. To the stirred acetyl chloride solution, kept at 50', was slowly added 49.9 3. (0.23 mole) of oephenoxymethyl~4-morpholineéthanethiol dissolved in 100 ml. of benzene. After the addition of the mercaptan, the reaction.mixture was stirred for 10 minutes, cooled and 140 ml. of water added. The aqueous layer was made strongly alkaline by the addi- tion of powdered potassium.carbonats. The benzene layer was separated, washed with water, then with a sodium.bicarbonate solution, again with water, dried over anhydrous sodium.su1fate, and the bensene removed in vacuum. The crude product was distilled under diminished pressure through a 50 cmi‘Vigreux column. The major fraction distilled at 136-137'0. (2 mm.)3 n3? l.h967. a yield of “2.3% based on allyl 2,3- epithiopropyl ether was obtained. Titration with 0.1-8 HCl indicated an.amine equivalent weight of 257.7. Calculated 259.5. Elemental analysis for 012321N038. Calculated: c. 55.55; H, 8.16; s, 53:3; 3, 12.36. Found: C, 55.63; H, 3.23; N, 5.14; 3, 12,35. 38. Preparation of 8-(lolllyloxyuethyl-a-norpholinoethyl) Mutants Hydrochloride /CH2'°32\ csz.ca-m2-oi-cs2-c':H-cxd2-s\ /o~sc1 ? cue-m2 (ls-o 6"3 A 6 a. quantity or 3-(1ca11yloaynethyloa- norpholinoethyl)thioacetate was dissolved in 25 all. of anhydrous ether and dry hydrogen chloride was passed into the solution. The resulting precipitate was re. crystallised tour tines tron isopropyl alcohol. the eonpound was obtained in a 66.2} yield and melted at 1h2.5~lM.STO. Elemental analysis for C12821N038-H61. Calculated: 6,118.71; H, 7.193 N, L76; 8, 10.84; as, 11.98. Found: 6, 148.94; H, 7.523 H, 5.653 8. 10.563 01, 11.90. 39. treparation of 8- ldllylomyuethyl-2-Piperidinoethyl) oaoetate “Erma CHZ-CH-GHg-O-CHQ-ffiomig-N /cn2 6.3-0 .313 This compound was synthesised in an identical manner to s-(l-ellyloxynetlwl-z-aorpholinoethyl)thie- acetate using piperidine instead or morpholine. me compound was obtained in a h8.6$ yield based on allyl 2,3«epith10propyl ether. The major traction distilled at 125-127’C. (a an); n§5 1.1:932. Titration with 0.1-)! 3C1 indicated an amine equivalent weight or 261.5. Calculated 257.5. Elenantal analysis for 013B23m28. Calculated: C, 60.61%; H, 9.00; N, 5.117; 8, 12.”. Found: C. 60.77: H, 8.981 N. 5.5% 8. 12.62. 40. Preparation of 8~ladllyloxynethyl-a-Piperidinoethyl) oaoetate Hydrochloride , ‘/ Giz-CHZ cuz-ca-cH2~o-cnz—fs~m2-N Cl-IZ-HCI 8 \\CH CH // ' 2' 2 0-0 to a 3 3. quantity or 8~(1—a11y10xynethyl-2~piperi- dinoethyl)thioscetate was dissolved in 12 ll. of anhydrous ether and the solution.was treated with dry hydrogen.chloride. The resulting alias salt was re‘ erystallised three times from a mixture (3:1) of ether and isopropyl sloshol. The waterial, obtained in a 58.&$ yield, melted at 90-92'0. Elemental analysis for 01332311023-301. Calculated: C. 53.12; H, 8.23; H, 4.793 3.. 10.91; 01, 12.06. round: 0. 53.04; H, 8.08) H, fl.661 8, 10.803 C1, 12.13. #1.. Preparation of 3-(2-Ilorpholino~l-Phenoxymethylethy1) mioaeetate Hydrochloride ~O~CI12-CH-CI-12~N ‘36]. me 8-(2-norpholino-l-phenoxynethylethyl)thioace- tats was prepared from 2,3-epith10propyl phenyl ether, norpholine and acetyl chloride following the experi- mental procedure for the synthesis or S-(l-allyloxy- uthyl-2-norpholinoethyl)thioacetate. the compound could not be purified by vacuum distillation as it decomposed- when heated in vacuum. Its hydrochloride salt was prepared by passing dry hydrogen ehloride gas into an ethereal solution or the compound and recrystal- liaing the resulting salt three tiles from a solvent mixture (1:1) or methyl alcohol and isopropyl alcohol. a yield of 35.15, based on 2, 3-epithiopropyl phenyl ether, was obtained. The pure product salted at 183- 185‘0. Elemental analysis for c15321m33-3c1. Calcu— lated: C, “.273 H, 6.68; N, 4.24; 8, 9.66; Cl, 10.68. round. c, 54.91. a. 6.71., x, 3.89; s, 9.76; CI, 10.37. 42. Preparation of 8- 2-Phenoxy-l~Piperidinomethylethyl) l‘h oacetate Hydrochloride /CHZ'CH2 \ -o-ca2-oH-m2-s\ csaoHCl f “2’532 0-0 $33 This thioester was prepared in the same manner described for the preparation of 8-(2-norpholino-l- phenomymethylethylhhioaoetate hydrochloride using piperidine instead of morpholins. After three rs- crystallisations from isopropyl alcohol, the material was obtained in a 29.9% yield, based on 2,3-epithio- propyl phenvl ether. It melted at 134.136'c. Elemen- tal analysis for 016323m23-Hc1. Calculated: c.58.h2; H, 7.351 I, 4.28; 8, 9.753 61, 10.47. round: c. 58.21; H, 7J0; N, Mllx S, 9.52; Cl, 10.38. ’43. Attempted preparation of s-é;(2-Allylo -1-Diethy1amino- me yl)ethyl ioacetate firm-marwae-ffi'flfla-N this compound was prepared in.a manner described under synthesis of 8~(loallyloxymethyl-a-aorpholinou ethyl)thioacetate, using diethylanine, allyl 2,3- epithiOpropyl ether and acetyl chloride as the starting materials. The product was purified by distillation under reduced pressure through a'TWx 1/?” column packed with a glass spiral. The nain.portion distilled between.101-101.5'C. (2 nus): nfi? 1.4753. A yield of 62.1! was obtained. Titration.with 0.1-HVHCl indicated an.amine equivalent weight of 232.7. Calculated 2h5.h. . Elemental analysis for CléH23N028. Calculated: C. 58.74: a, 9M: N, 5.71; a, 13.07. Found: c, 57.76; H, 9.013 R, 5.29; 3, 12.3%. Apparently some slight decomposition took place either during or after the distillation. ' #4. Infrared Spectra The infrared spectra of all the mono- and diepi- sulfides synthesized and the mono- and diepoxides from which they were prepared were determdned. A Perkinpfllmer Infrared Spectrophotometer was used. A thol null between salt plates was prepared when the sample was a crystalline compound. A film between salt plates was used when the sample was a liquid. 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KSCN—é s—o-cna-cn-cne + Kocu R '- CH3, 02115, 1-C3H7, 11.03117, 11-64119, and C615 In the present work dealing with.more complex molecules, and especially with the higher:moleculsr weight dispoxides as the starting material, it was found that little reaction, it any, took place under the same conditions. This is probably due to the low solubility of the epoxide in the aqueous potassium thiocyunste solution at room.temperature. Jacobs' synthesis of 2,3—epithiopropyl phenyl ether in which water was used as the only solvent could not be 63. 64. duplicated. An attempt to conduct this reaction at higher temperatures (ho-50's.) resulted in a very low percent conversion to the thiirane. Dioxane was re- ported (51) to be a suitable solvent to use with water in the synthesis of styrene sulfide. The reaction temperature used in this case was 60’0. Attempts to make the dithiiranes from resorcinol‘diglycidyl ether, and the diglycidyl ether of bisphenol A, using a 50% aqueous dioxane solution of potassium thiocyanate at roan temperature resulted in very low conversion to the corresponding thiiranes. When higher reaction temperatures were applied (60‘C.), polymerization and/ or deems-inch or the prosuxnably formed dithiiranes took place. me use or an aqueous ethanol solution in the preparation of cyclohexene sulfide has been reported by B. E. Van melon (52) who carried out the reaction at room temperature for an extended period of time. ihsn this solvent combination was used, the preparation of 2,3-epithiopropyl phenyl ether was accomplished without difficulties. 0n the other hand, allyl 2,3» epithiOprOpyl other was obtained in good yield using only ~later as the solvent. Apparently, the solubility or miscibility or its corresponding epoxide in aqueous potassium thiocyanate was sufficient to make the reaction proceed at a reasonable rate. In the preparation of p-tert butylphenyl glycidyl ether, the solubility of the starting epoxide in a 65. water-ethanol mixture was not sufficient to obtain the proper conditions for reaction to occur at a measurable rate. Therefore, a volume of acetone equal to the volume or water used was added with the ethanol. Under these conditions the reaction took place, but the yield was low. Better yields would be expected when acetone and some water are used at the solvent system, and the reaction is conducted at alightly elevated temperatures. Since p-tert butylphcnyl 2,3-epithiopropyl ether can be prepared and distilled. the lower alkylphenyl 2,3-epi- thiopropyl ethers could become available as well. me first dithiirane obtained in this study was path from resorcinol diglycidyl ether. In sons pre- liminary work, attempts had been made to isolate em or the n-bie(2,3-epithiopropcxy)benzene by distillation from the partially polymerized product. he latter material was obtained from the reaction, at elevated temperatures. or the corresponding epoxide, with potassium thiocyanate in dioxane and water as the solvent lnixture. In no case was this distillation successful. Fortunately. this dithiirane, as well as aeveral others, turned out to be crystalline solide which could be purified by recrystallization from ethanol without nuch trouble. In the preparation or n-bis(2,3-epithiopropoxy)benzene. an ethanol-water mixture was used as the solvent nixture with a rather 66. large excess of potassium thiocyanate. This procedure I was employed as it was intended to add a second por- tion of the resoroinol diglyoidyl ether after the reaction had been allowed to stand overnight. However, such a large quantity of a white precipitate was formed in the initially clear reaction mixture that is was thought advisable to recover the dithiirane formed, rather than add additional quantities of the dicpoxide. however, it is probable that the large excess or potassium thiocyanate contributes to a higher conver- sion at the epoxide to the thiirans. Further, the extraction or the product with benaene could be elimi- nated. me crystalline product could be recovered by filtration, washed with water, dried and recrystal- lised tron ethanol. his procedure was later followed in the synthesis of 2,2-bisfp.(2,3-epithiopropcxy) phenyi_7pr0pane. . the solubility of hydroquinone diglycidyl ether in an ethanol~water mixture was round to be very low. Acetone appeared to be a better solvent, but at room temerature the diepoaide crystallised rather readily tron an acetone-water mixture. Ithe reaction was there- fore run at an elevated temereture for a short period of time. The product obtained melted at Ems-136.5%. taxis, howover, was only one isomer out or the possible two that could be formed. The Dutch chemists , Werner . 67. and Parenhorst (3,53), reported that two isomers are formed in the reaction of excess epichlorohydrin and hydroquinone. Hydroquinone diglycidyl other has two asymtrio carbon, atoms and occurs in two diastcreoo isomeric forms, a racemate ands Ieso form. Werner and Farenhorst (3.53) were able to separate the die astercoisoncrs, which were present in approximately equal quantities, by fractional crystallization.. The lower meltingisomer (m.p. 89.5-90.5‘6.) dissolved much more readily in various solvents than the higher melting one (mp. llB-llQ‘C.). By analogy, it would be expected that p-bis(2,§-epithio;‘ropoxy)benzene would also exist in two isomeric forms. Since the starting material, in this work, was a mixture of the isomers ot‘ hydroquinone diglycidyl ether, a mixture of the isomers of the corresponding dithiirane was obtained, together with some or the unreacted and half reacted diepoxide (both isomers). This made the separation or all the product isomers extremely difficult. The only product that couldbe isolated must therefore be the high melting isomer of p-bis(2,3-epithiopro~ pouy)benzene (mp. l3u.5-IBG.S’C.). It would be of interest to repeat this aims... synthesis with both the low melting and high melting hydroquinone diglyci- dyl other as individual starting tutorial. It would be expected that the low melting diepoxide would give 68. the low melting dithiirane and the high melting hydro- quinone diglycidyl ether. the high melting p-bis(2,3- epithiopl’opmhensene. This result is predictable became of the stereospecitic nature or the reaction. Van Tension (54) has presented evidence supporting a mechanism for such e sterecspeciric reaction illus- trated in the alicyclic series. _ s I /CH2\C{§ - v.1. /CH2\c--s-c§ (mafia |,,.0 + scs flmahx ———3' \m /c\H \ /‘.-—,.H 2 “”2 b (1) cs .3 - fl 2 1 £32 3 - (/ ) \ 3\c: N" \ ( ) \ w I CH2 n __ . 7 C32 31 l“. e e 7\ (:32. ‘o scan (11) (In) . H /°"2\ ; (CH2)n 1/3 + ‘o-c-N 2/ “ 69. no mechanism imlies two lalden inversions. the ring Opening of cyclohexene oxide (n . 2) has been shown to proceed, in all cases studied, with exclusive Roldan inversion in acid, neutral or basic aedia. nus, the ring opening or this oxide leads to the anion or maohydroxycyclohexyl thiocyanate. ligration or mmmmmmmmygonmmoyono interlediate (n), which Price and Kirk (55) later proved was present by isolating its ll~(pdnitrobenzcyl) derivative. some. in the torntion or the anion or trm-E-nercaptocyclohexyl cyanate, which is favorably oriented for a m ring-closure to yield the cyclic minds and cyanate ion. turtherlore, Price and Iirk (55) observed that the reaction of potassium thiocyanatewith D(+)-2,3-epoxy~ butane produced the L(-)-2, 3-epithiobutane. substan- mm the mechanism proposed. Because at the stereospeciricity in the reaction of epoaides with thiccyanate ions, the new for: of hy- drequinone dislyeidyl other would become a need form in the panda, B-epithicpropoaty)benzene and the race-ta or the «napalm ether would become a racemc mixture. Werner and laremorst (3.53) were unable to cmletely separate the issuers of resorcinol diglycidyl ether nor the isomers of the diglycidyl ether of bisphenol A. It caplete somersion or these compoums to the \l m 1.. 70. corresponding dithiiranes were accomplished, their cmlete isomer separation may be possible with the sulfur oomounds. Considerable difficulty was encountered in the preparation of 2,2-bisfp-(2,3—epithiopropoxy)phenyl_] propane with sufficiently high purity to obtain a satisfactory elemental analysis. When the reaction was conducted at temeratures below 60'0. for an extended period or tile (11 hours), a crystalline material was obtained melting below 92‘6... which was low in sulfur content. Repeated recrystallization from ethanol, Isthml, tetrshydrofuran and benzene and mixtures of these failed to improve the purity of this laterial. It was not until (the reaction was forced to very near completion that a pure compound could be obtained after a single recrystallisation methanol. * he attempts were made to prepare bis-(2,3aepi- thiopropyl)ether from the corresponding diglycidyl ether. The latter was synthesised- in low yield following the method described by mdley (7’) . In the initial synthetic attelpt. the diglycidyl' other used as the starting material was somewrnt high in hydro- lysable chlorine content (0.15%) and rather high in epoxy equivalent weight (70.7, theory is 65). Some gel formation occurred in the early stages of the 71. motion conducted to synthesize the dithiirane. “tented purification of the crude dithiirane under reduced pressure resulted in its polymerization. A second synthesis attemt with purer diglycidyl ether (0.235 hydrolyaable chlorine; epoxy equivalent weight 65.9) resulted in no gel formation during the reaction and the resulting dithiirane could be distilled. What was later observed in the preparation of other epi- suli'ides was again substantiated hrs, nanny, that pure starting materials are necessary for the reaction to proceeds-catnip with starting materials or high purity. the reaction of diepoxides with potassiua _ thiocyanate any be conducted for longer periods of tins and at higher reaction temperatures without detrinentel streets and increased yields. lhen diglyciivl ether of high purity is employed, the bis(2,3-epithiopropyl) ether can be obtained pure, since the last attemt to obtain this naterial cane very close to synthesizing it in a pure tom. L considerable experimental work was conducted in an effort to synthesise two related thiiranes, lenethyl—l.2~epithio-h-isopropenylcyolohexane (linonene nonoepisultide) Ind 2,6,6-trinethyl-2.3-epithiobi- cyclo[3.l.l_7heptane (c-pinene episulride). The method or Snyder, Stewart and Ziegler (l) was tried using a variety or solvent combinations and in all 72. cases two layers foraed in the reaction mixture. ‘11:. conversion of the epoxide to its sulfur analog was low. Iith elevated reaction temperatures, the product polymerized readily, while part of the starting nets- riel was recovered. ' The use of the:aethod of Culvenor, narlnland faueacker (9) resulted in only the recovery of starting asterial. The procedure of Bordwell and.Anderson (10) yielded the l-Iethylnl,zeepithio—h-iscpropenylcycloo hexane in low yield. flhe sane procedure, however, gave a polyasric asterial innthe attempted preparation or 2,6,6-trimethyl-2,3-epithiobioyolof3.l.l_7heptane (uppinene episulfide). Infrared Spectra of Oxiranes and.Thiiranes While it was not the main objective of this inves- tigation to assign all the frequencies of the infrared spectra of the thiiranes synthesised, it was thought to be of value to compare their infrared spectra with those of the corresponding epoxies. It was found that certain consistent differences exist in.the infrared spectra of the two classes of compounds. after studying the infrared spectra of twenty-six epoxy compounds, Patterson (56) proposed that the epoxy bands are present in the 11.0 and 12.0‘aicron region. the bands vary from 10.52 (950 om.'1) to ‘, ‘0 he 73. ' 11.58 microns (863 cud) in the 11 micron region, and fro. 11.57 (864 en.'1) to 12.72 microns (786 sail) in the 12 micron region. he compounds reported by Patterson were also used in this investigation, namely, allyl glycidyl ether and phenyl glyeidyl ether, and the abscrbtion spectra determined in this work are in good agreement with that previously reported. Absorb- tion in what Patterson refers to as the 12 micron re- gion were found in all the infrared spectra of the cairane conxpcunds examined in the present study. With several compounds, a double absorbtien was noticed in this general area. In all cases, these bands were absent in the corresponding thiirane cowo‘mds (Table IV) with the exceptim of an absorbtion at 11.69 microns (855 en.'1) in I—bis(2,3-epithiopropoa:y)benaens which is due to a meta substituent on the arouatic mcleus. Although the double absorbtion in the epoxy compounds is not too distinct in all cases, it is highly probable that there are two bands due to the em group in the 12 micron region, instead of a single one as initially reported by Patterson. It is quite apparent that these absorbtions disappear when the oairane oxygen is replaced by a sulfur atom. (Table xv, first two columns). In the 11 micron region, the epoxy compounds in- vestigated me a hand between 10.86 (921 curl) and 714. 10.91} microns (911$ crud), with the exception of limo- nene monoxide. me intensity. of this absorbtion due to the epoxy ring diminished greatly or almost disappeared when going to the corresponding thiiranes. (Table IV, second two column). Uhy the absorbtion does not disappear entirely in the sulfur compounds is not clear. It was further observed that a weak absorbtion between 8.80 (1138 cm.'1) and 8.88 ailerons (1128* cm."1) is present in all epoxy conpounds'reported here. 'mis absorbtion is very weak in allyl glyoidyl ether and p-tert butylphenyl glycidyl other, but very well definite in the spectra of the other epoxy compound. this band has not been reported in the literature as an sbsorbtion due to the epoxy ring, at least not in coupounds of sons comlexity. An absorbtion in this vicinity at 8.60 microns (1165 earl) has been reported, however, for ethylene oxide (58). The thiiranes obtained from the epocaides synthesised during the course of this study do not show absorbtion between 8.80 and 8.88 microns. (Table Iv. fifth and sixth columns). me band at 8.60 (aicrons present in ethylene oxide does not appear to be present in ethylene sulfide either (to)- A band characteristic of the epoxide ring at about 8 .nicrons was reported by Patterson (56) and earlier by Field, sole and woodford (57). this 75. absorbtion was present in all the exit-ans compounds eunined in this work, although it was very weak in the case of limene nonoxide. Ehe corresponding thiiranes all have absorbtions in the same region, although less intense in the case of allyl 2,3éepith10propyl ether. In the cases of 1s- and p—bis(2,3—epithiopropoxy)bensene an additioml absorbtion seels to be present at 8.05 .1ch (12M curl) and 8.02 microns (12118 mail) which was not present in the corresponding spay cur- pcunds.. 'lhe entire region armm 8 morons is too cos- plicated, however, to base any definitive conclusions on the limited data available. . A strong absorbtion at 13.2 licrens. reported by um»... (56) in epoxy others, was not present in the hydroosrhORethers. Hereportedasinilarbandinthe m esters, in l,h-pentadiene dioxide and one Just detestable in butadiene monoxide. It also appears in epichlm-ohydrin, propane oxide and octane-l-oaide. Although the band is relatively mach weaker than the basis in the 11 and 12 aicron region, the possibility thatthisisduetotheoairanerimcannotbeimcred according to Patterson. Such bands were found in the Isle region in sons of me epoxy solpounds studied. may are least pronounced in the allyl glyeidyl ether at 13.01 aicrons (769 «.31). p-m-e butylphenyl glycidyl ether at 12.98 111ch (771 «71). hydro- 76. .quinone diglycidyl ether at 13.21 microns (757 ems'l) and limonene monoxide at 13.19 microns (758 cn.'1). In all these cases, this absorbtion is not present in the sulfur analog, which supports the possibility that the absorbtion.ar0und 13 microns is caused by the oxirane group. lbreover, changes also occur in the 12 micron region in.going trom.the epoxide to the corresponding thiirane in the case or resorcinel diglycidyl ether and the diglycidyl ether of bisphenol A. these changes are, however, of such nature that the interpretation is very difficult. In a search for a bend specific to the thiirane group, it see found than an abscrbtion at about 9.5 microns (105“ on.’1) is very probably due to the thi~ irane group. this at least seems to be the case in the thiiranes derived tree.glycidyl ethers. In.all these compounds, an absorbtion was observed at about 9.5 microns, which is not present in the epoxy com- pounds. The only apparent exception is the resorcinol diglycidyl ether sulfur analog. Here a strong absorb~ tion was found at 9.5 microns in both the oxirane and thiirene compounds. Table iv; the last two columns, summarizes these data in.nore detail. Finally, some of the thiirans compounds have an absorbtion at about 10.4-10.5 microns which is not present in the epoxies. This band is especially strong 77. in.nsbis(2,3-epithiopropoxy)benzene, but was also quite easily observed in several of the other episulfides. In.summary, it can be said that the epoxy absorb- tions in the 11 and 12 micron region as reported by Patterson (56) diminish greatly or disappear, respec- tively, when the oxirane is converted to the correspond~ ing thiiranc. 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Aninothiolo - Derivatives of Thiironeo Tho rooction botwcon thiiranoo and secondary amines io rothor straightforward as long no certain conditions oro oboorvcd. those conditions hovo boon.reportod by Jacobo and Schnotz (61) and oorlior by Era: (an). A nonionizing oolvont should bo olploycd and o molar oxcooo of tho omino should.bo prooont during the roac- tion.‘ Difficultioo onoountorod, holotor. ooro tho docomp position or oovorol of tho aminothiolo during purifica- tion by distillation, tho hydrooccpic choroctor of tony or thoir hydrochloridoo. and tho failuro to obtain cryotollino Iolto or nony of tho olinothiolo. In.gcnorol, oryotollino hydrochloridc colts could ho fornod from tho aminothiolt hoood on piporidino and norpholino, olthough in one‘ coco. o-(ollyloxy)mothyl-l- piporidinoithoncthiol hydrochlorido, tho compound was too hydroocopic to obtoln it in.tho puro form. Sooondory'oldnoo which do not hovo ring otructurco u do norpholino ond pipcridino oppoor to react with tho thiironoo without difficulty. Honovor. as noticed by Jacobo and Bchnetz (61). tho olinothiolo which ore tormd docomooo in tho tin]. diatillotion into tho starting notorialo which are rooovcrod. In this otudy, on.cttompt was node to isolate tho salts of various 80. acids or l-diothylamino-B-phcnoxy-z-propanethiol and or l-di-n-butyloninc~3-phcnoxy-2-propansthicl. The acids used woro hydrochloric acid, p-tolucne sulronic ccid, naphthaleno sulfonic acid, sulfuric acid, picric acid and phosphoric acid. In no case could a.crysta1- lino compound bo obtained which nado further purifi- cation inpossiblo. .Duo to these difficulties, tho locust or aminothiolo synthesized was limited. It thoroforo was decided to proporo o for amino-norcaptans tron diethylonino and too or the thiironos, starting with very pure reactants so thot o puro product would be obtainod without crystallization or distillation. Ehis approooh Ins indeed successful in.tho case of l~diothylondno-anphonoxy-2-proponethiol, but did not result in,o pure compound uhon.diothylamino was ollowed to react uith ollyl 2.3-cpithiopropyl other. .Pinolly. it should be roportod that by analogy to the findings of Snyder. Stewart and Ziegler (l) the anisothiols ore assumed to consist largely, it not solely, at the secondary norcaptan structure as shown in.Tables II and II A. {Aninothioocototos Tho-o compounds uero proparod by the reaction of the ominothiols, discussed in the previous section of this thesis, and ocetyl chlorido (a). The aminothio- 81. acetates are less hydroscopic and more stable than their corresponding aminothiols. For instance, it was possible to purify by crystallization the s-(l-allyl- oxymethyl-e-piperidinoethyl)thioacetate hydrochloride, which could not be done with the corresponding amino- mercaptan. Further, the 3-(l~allyloxynethyl-2- morpholinoethyl)thioacetateand the similar piporidino compound could be purified by distillation. This again.was not possible with the corresponding amino- thiols. Even the related diethylaminothioacetate could be distilled, without readily splitting out diethylamino, as was the case with the aminothiol fron.which this com, pound was prepared. Some decomposition must, however, have occurred in the distillation of 3:1712-allyloxy-l- diethylaminomethylhthyl Jthioacetate, since the compound was not obtained in.good purity. A purer product might be obtainable with a more efficient column under higher vacuum. unfortunately, the salts of this compound did not for: a crystalline material, and further purification.was not possible. Purification by distillation of the s-(e-phenoxy- l-piporidinomethylethyl)thioacotato and the correso pending norpholino compound was not possible due to rather extensive decomposition. Their hydrochloride salts, however, were crystalline solids which could be purified readily. Further details on the amino. 82. thioacetates synthesized during this investigation are sumarized in Table IV. 1. 2. 3. 5. 6'. 7. 9. 10. 11. 12. 13. ll}. 15. REFERENCES no 3. 311311025 Jo no Stdwal‘t and Jo Bo Ziegler, J. Am. Chemo 300 o ’ g2, 2672 (19“?) 5 I. 1.. Jaoobs, Ph.D. mesis, llichigan State Uni-"I‘llty. 1959o E. G. 6. Horner and E. Paronlwrst, nos. Trev. can" §1, Mo (1948 ). h. 0. Clinton, U. I. 6Salvador and 8. c.1ashowski, Jo ll. Ch... $00.. 1.6.! 5121 ‘19“)o s. n. Slash and r. 1!. A1 at U. 3. Patent 2,221,818 (ions). qul ' 8. ll. Boosehens and P. H. nor-ans, Bull. doc. .06), 125“ (1925): C. A. 21.55 (1927): R. Dudley, U. 8. Patent 2,169,681; (1919). J. I. Roach and H. Uittcoff, U. 8. Patent 0. 3. 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