United States Patent (19) 11 4,267,375 Maasbol et al. 45 May 12, 1981 54 PREPARATION OF THIOETHERS OTHER PUBLICATIONS 75) Inventors: Alfred G. Maasbol, Hamburg, Fed. I. Ruderman et al., J. Amer. Chem. Soc., 71, pp. Rep. of Germany; Lothar G. Dulog, 2264-2265, (1949). St. Martens Latem, Belgium Morrisson and Boyd, Organic Chemistry, 2nd edition, (1967), pp. 29–30. 73) Assignee: s.a. Texaco Belgium in.v., Brussels, T. Todsen et al., J. Amer. Chem. Soc., 72, pp. Belgium 4000-4002, (1950). Berichte Deutsch. Chemie, vol. 1, pp. 587-591, (1935), (21) Appl. No.: 945,273 Berlin. 22 Filed: Sep. 25, 1978 D. Gregg et al., J. Org. Chem., pp. 246-252, (1950). M. Malinovskii, Epoxides and Their Derivatives, pp. Related U.S. Application Data 131-136, (1965), Jerusalem, Daniel Davey & Co. Primary Examiner-Glennon H. Hollrah 63 Continuation of Ser. No. 703,045, Jul. 6, 1976, aban Assistant Examiner-M. C. Eakin doned. Attorney, Agent, or Firm-Carl G. Ries; Robert A. 30 Foreign Application Priority Data Kulason; Carl G. Seutter Nov. 19, 1975 GB United Kingdom ............... 47582/75 57 ABSTRACT .. 51 Int. Cl. ............................................ CO7C 149/30 Thioethers may be prepared by reacting a thiol, such as thiophenol, with an alcohol (having electron donor 52 U.S. C. ......................................... 568/57; 568/58 groups in the alpha or beta position to its hydroxyl 58 Field of Search ........................ 260/609 E, 609 R group) such as phenyl-1-hydroxy-phenethylsulfide. Re 56) References Cited action is carried out in the presence of a Lewis Acid U.S. PATENT DOCUMENTS metal halide, typically zinc chloride. 2,745,878 3/1956 Mavity ............................. 260/609 E 3 Claims, No Drawings 4,267,375 1 2 found not to undergo reaction with thiols in the pres PREPARATION OF THIOETHERS ence of Lewis acid metal halides. When, however, an electron-donor substituent is This is a continuation of application Ser. No. 703,045 present in the a- or 6-position to the hydroxy group, filed July 6, 1976, abandoned. reaction with a thiol occurs readily, in some instances at room temperature, and the required thioether is ob Field of the Invention tained in large yields. This invention relates to a method for the preparation A variety of electron-donor groups can be present in of thioethers. More particularly, this invention relates the a- or 6-position to the hydroxy group of alcohols to a method for the preparation of certain thioethers by 10 which can be employed in the method according to the reaction between a thiol and a substituted alcohol. present invention. For example, the electron donor DESCRIPTION OF THE PRIOR ART group can be an ether (e.g. alkoxy) or thioether (e.g. alkylthio) group, or a substituted amino or phosphino Thioethers and polythioethers have been employed group. or suggested for employment as high temperature lubri. 15 For instance, the electron-donor group can be a cants or as oil additives for various purposes, but their group of the formula use has been hindered by the unsatisfactory methods available for their preparation. -OR, -SR or -PR2 A well known method for the preparation of thioe thers is an adaptation of the Williamson synthesis in 20 in which R is a substituted or unsubstituted akyl, aryl, volving reaction of an alkali metal derivative of a thiol aralkyl or alkaryl group. Alternatively it can be an with an alkyl halide. aromatic or substituted aromatic group. Ruderman in J. Amer. Chem. Soc., 71, 2264 (1949) In general it is preferred that the electron-donor sub described the formation of thioethers by the reaction of 25 stituent should be in the a-position rather than in the thiols with "phenol alcohols.' A specific example of f3-position since the reactivity of a-substituted alcohols this is the reaction between 1-butane thiol and 2 is greater than that of the 13-substituted alcohols and the hydroxy-al,a mesitylene diol to form 2-hydroxy-all,a3 desired thioethers can thereby be more readily ob bis(butylmercapto)mesitylene. tained, such as at lower reaction temperatures or in 30 shorter reaction times. CH2OH CH2SBu According to one preferred embodiment of the in OH OH vention, the electron-donor substituent can be an aro matic nucleus or substituted aromatic nucleus. A pre + 2 BuSH-Ge. ferred class of alcohols containing such substituents has CH3 CH2OH CH3 CH2SBu. 35 the general formula Reaction is exothermic at room temperature catalysed with hydrogen chloride or boron trifluoride. Another method for the preparation of thioethers is described by Todsen et al. in J. Amer. Chem. Soc., 72, 4000-2 (1950). Epoxides are reacted with thiols to open the epoxide ring with formation of hydroxy groups and in which R is an aromatic group or an arylmethyl thioether groups on adjacent carbon atoms. This reac group; and R2 and R3, which can be the same or differ tion is carried out in the presence of zinc chloride at ent, are each hydrogen or an aliphatic, cycloaliphatic or elevated temperatures. 45 aromatic hydrocarbon or substituted hydrocarbon There is therefore a requirement for a method for the group. preparation of thioethers which is convenient and does Preferably, R is a phenyl or benzyl group, R2 is hy not require complex reactants or corrosive reaction drogen or an alkyl group and R is hydrogen. Particu Systems. m larly preferred alcohols having the general formula set The object of the present invention is to provide a 50 out above are benzyl alcohol, 1-phenethyl alcohol or novel method for the preparation of thioethers. 2-phenethyl alcohol. Of the above-mentioned aralkanols, it is found that SUMMARY OF THE INVENTION 1-phenethyl alcohol reacts with thiols more readily than The present invention provides a method for the 55 benzyl alcohol and the latter compound reacts more preparation of thioethers which comprises reacting a readily with thiols than does 2-phenethyl alcohol. thiol with an alcohol having an electron-donor group in According to another preferred embodiment of the the a- or 3-position to its hydroxy group in the presence invention, the electron-donor group is a thioether of a Lewis acid metal halide as catalyst. group, which is most preferably located on the carbon 60 atom adjacent to the hydroxy group of the alcohol, i.e. DESCRIPTION OF SPECIFIC EMBODIMENTS in the d-position. It is essential that the alcohol used in the present A particularly preferred class of thioether-substituted invention should have an electron-donor group (nucleo alcohols have the formula philic group) in the d or 3-position to the hydroxy group. When such groups are missing, the reaction 65 between alcohol and thiol does not occur, For example, RS-CH-CH-R6 II alkanols such as n-butanol, isobutanol or t-butanol, and OH SR unsaturated alcohols, such as allyl alcohol, have been 4,267,375 3 4. in which R is an aliphatic, cycloaliphatic or aromatic may have aromatic substituents, forming araliphatic hydrocarbyl or substituted hydrocarbyl group; and Rs groups, e.g. benzyl, and aromatic hydrocarbyl groups and R6, which may be the same or different, are each may have aliphatic substituents, forming alkaryl groups, hydrogen or an aliphatic, cycloaliphatic or aromatic e.g. tolyl, or xylyl. Electron-attracting substituents hydrocarbon or substituted hydrocarbon group. should, of course, be avoided. In preferred compounds of the formula II, R is an The catalysts used according to the invention are alkyl or aryl group, and one of R5 and R6 is hydrogen Lewis acid metal halides, preferably chlorides, although while the other is an aryl, chloromethyl or hydroxy fluorides and bromides may also be used. A particularly methyl group. Such compounds may, for example, be preferred catalyst is zinc chloride, but other halides of produced by reacting an epoxide and a thiol. Such a O polyvalent metals, such as aluminium chloride, magne reaction is known to involve opening of the oxirane ring sium chloride, stannous chloride, ferrous chloride, fer of the epoxide and formation of an a-hydroxy thioether ric chloride, antimony trifluoride, antimony pentafluo grouping. For instance, it is known from the above ride, magnesium bromide or aluminium bromide can mentioned paper by Todsen et al. in J. Amer. Chem. also be used. Soc., 72, 4000-2 (1950) that epichlorohydrin reacts with 5 The reaction temperature depends upon the nature of n-butane thiol to form 1-butylthio-3-chloropropan-2-ol. the reactants, the amount and nature of the catalyst, and the presence or absence of a solvent. In some instances, reaction will proceed at room temperature, while in CH2-CH-CH2C-G-CH2-CH-CH2Cl other instances, elevated temperatures, e.g. 60' to 130 N / C. are preferably employed in order to provide a more O SBu OH rapid reaction. Where a solvent is employed, it is conve nient to conduct the reaction at the reflux temperature It has in fact been found that various epoxides undergo of that solvent. The fact that temperatures as low as such a reaction with formation of both possible isomers. room temperature can be employed in some instances, is For example, it is possible to isolate both 1-butylthio-3- 25 an advantage of the present invention. chloropropan-2-ol and 2-butylthio-3-chloropropan-1-ol The reaction according to the invention can be car by reacting epichlorohydrin with n-butane thiol in the ried out in the presence of a solvent or in the absence of presence of zinc chloride. Similar reactions are under a solvent. When a solvent is used, it should, of course, gone by other appropriately-substituted epoxides, such be inert under the reaction conditions.