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Home , Hydroxy group, Phenethyl alcohol

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, 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 , such as

, with an (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 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 in the pres PREPARATION OF THIOETHERS ence of Lewis acid metal halides. When, however, an electron-donor 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 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 (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 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 " 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 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 has CH3 CH2OH CH3 CH2SBu. 35 the general formula Reaction is exothermic at room temperature catalysed with 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 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 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 , 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 , 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-, or t-butanol, and OH SR unsaturated alcohols, such as , 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 . 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 , 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 . 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. Suitable solvents as styrene and glycidol. 30 include, for example, , especially aromatic It is accordingly possible, by employing an appropri hydrocarbons, and an especially preferred solvent is ate excess of thiol, to convert an epoxide into a vicinal bis-thioether. Suitably, the oxirano ring is opened to , which has a convenient reflux temperature of give a mixture of the isomeric a-hydroxy thioethers. about 80° C. (the proportions of which will depend upon the reac 35 Thioethers can be employed as antioxidants, or as tants) and the isomeric a-hydroxy thioethers then react additives in oil compositions. Thioether alcohols are with further thiol to form the vicinal bis-thioethers. also useful as intermediates in the synthesis of deter According to a further preferred embodiment, when gents. For instance, they can easily be oxidised to 6 a hydroxymethyl or chloromethyl substituent is adja hydroxyalkyl sulphoxides, which can be employed as cent to the oxirane ring, it is possible to react such a 40 non-ionic detergents. substituent with more of the thiol, with formation of a The present invention is further illustrated by the 1,2,3,-tris-thioether. For instance, epichlorohydrin and following Examples: glycidol will both react with a 3-molar excess of a thiol EXAMPLE 1 to form propan-1,2,3-tris-thioethers. The nature of the thiol employed in the method ac 45 1.2 g (5 m moles) of phenyl-1-hydroxyphenethylsul cording to the invention is of less significance than the phide, 5 cc of thiophenol and 1 g of zinc chloride are nature of the alcohol. The only essential is that it should refluxed in 10 cc of benzene for 3 hours. Evaporation not contain any substituents that interfere in the reac and crystallization from n-hexane yield 1.28 g (70%) of tion according to the invention. 1-phenyl-1,2-bis(phenylthio)ethanae, m.p. 57 C. after Preferably the thiol has the formula 50 recrystallization from hexane. R-SH EXAMPLE 2 1.2 g (5 moles) of phenyl-2-hydroxyphenethylsul in which R is an aliphatic, cycloaliphatic or aromatic phide, 5 cc of thiophenol and 1 g of anhydrous zinc hydrocarbyl or substituted hydrocarbyl group. For 55 chloride are dissolved in 10 cc benzene and refluxed for example, R can be an alkyl group, such as n-butyl or 3 hours. After evaporation and crystallization from n-dodecyl, or an aromatic group, such as phenyl. Dode n-hexane 1.22 g (73%) of 1-phenyl-1,2-bis(phenylthio)e- cyl mercaptain and phenyl mercaptan are particularly thane are obtained, m.p. 56.5-57.5 C. after recrystalli preferred thiols. zation from hexane. When, in the compounds of the formulae set out 60 above, R, R2, R3, R“, R5 and R6 represent substituted EXAMPLE 3 hydrocarbyl groups, the nature of the substituent 1.5 g of anhydrous zinc chloride are dissolved in a groups is of minor significance. It is only required that solution of 10 cc of thiophenol in 150 cc of benzene at they should not interfere in the reaction between the reflux temperature. 5 cc (43.5m moles) of hydroxy and thiol groups in the presence of the metal 65 in 50 cc of benzene were added dropwise within one halide Lewis acid catalysts. hour. After completed addition, the solvent and unre The substituents may, for instance, themselves be acted Starting materials are removed by heating and hydrocarbyl groups, i.e. aliphatic hydrocarbyl groups steam distillation. The residue is extracted by ether, and 4,267,375 5 6 the ethereal solution is dried and evaporated. A yellow oil is obtained which crystallized on standing. Recrys EXAMPLE 8 tallization from heptane yields 8.0 g (57%) of 1-phenyl 1 cc of 2-phenethylalcohol, 2.3 cc of thiophenol and 1,2-bis(phenylthio), m.p. 56-57 C. 1 g of zinc chloride are dissolved in 25 cc of benzene 5 and refluxed overnight (~20 hours). Vpc analysis indi EXAMPLE 4 cates 20-30 percent conversion into phenyl-2-pheneth 50 g (66.5 cc, 0.25 moles) of dodecylmercaptan, 1 g of ylsulphide. Continued reaction did not cause much zinc chloride and 7.7 g (6.5 cc, 0.083 moles) of epichlo increase in yield. rohydrin are heated in an oil bath at 130' C. for seven 10 EXAMPLE 9 hours, during which time gaseous hydrogen chloride is A solution of 6.5 g (6 cc, 60 m moles) of thiophenol, given off and water separates. After standing overnight 5.2 (5 cc, 48 m moles) of benzyl alcohol and 1 g of zinc at room temperature (about 15 hours), a white solid had chloride in 50 cc of benzene is stirred at room tempera formed. ture for 20 hours. Vpc-analysis indicated no change. Recrystallization from 1 liter of yields 43.0 g 15 After refluxing for seven hours, all benzyl-alcohol had (80%) of a white solid, m.p. 35-40 C. disappeared, while small amounts of thiophenol were From the evaporated mother liquid another portion still present and one major product had formed. The (2.1 g) of the desired product 1,2,3-trisdodecylthiopro solution is extracted with aqueous acid, sodium hydrox pane is obtained by recrystallization from 150 cc of ide and water, dried over a molecular sieve and evapo -ethanol mixture (2:1). Total yield: 45.1 g 20 rated. Recrystallization yields a white solid, m.p. (84%). 38-39 C. (80% alcohol). The comparison and mixed melting point determination with an authenic sample EXAMPLE 5 (38-39 C) indicate the identity. of the product as 1 g of anhydrous zinc chloride is dissolved with phenylbenzyl sulphide. warming at 50° C. in 60 g (66.5 cc, 0.25 moles) of dode 25 Results comparable to the above (e.g. Example 1) cyl mercaptan. At a temperature of 50-60' C., 12 g (10 may be attained when the following Lewis are cc, 0.12 moles) of epichlorohydrin are added dropwise. used The mixture is kept at 50°-60° C. for another hour and then heated at 85°-90° C. for 20 hours. By this time 1-chloro-3-dodecylthiopropanol-2 is the only reaction 30 Example Lewis acid 10 aluminium chloride product (as indicated by the infra red spectrum). The 11 magnesium chloride mixture is heated for five hours at 130 C, during which 12 stannous chloride time water is separated and HCl gas is given off. 13 ferrous chloride 14 ferric chloride After 15 hours standing at room temperature over 35 15 antimony trifluoride night, a yellow oil separates and is crystallized from 16 antimony pentafluoride alcohol, yielding 38.5 g (72%) of 1,2,3-trisdodecylthio 17 magnesium bromide propane. From the evaporated mother liquor, another 8 aluminium bromide portion of 9.0 g is obtained by recrystallization from 300 cc of methanol-ethanol mixture (2:1). These non-limiting examples demonstrate that thioe Total yield: 47.5 g (89% basis dodecylmercaptan). thers may be prepared in good yield under mild condi tions from thiols and alcohols having electron donor EXAMPLE 6 groups in the alpha or beta position to their hydroxyl 37 g (0.5 moles) of glycidol (epoxypropanol), 101 g groups. (0.5 moles) of dodecylmercaptan and 1 g of anhydrous 45 Obviously, many modifications and variations of our zinc chloride are heated in an oil bath at 100-120' C. invention as hereinbefore set forth may be made with for one hour. out departing from the spirit and scope thereof. There Recrystallization of the crude product from 1.4 liters fore only such limitations should be imposed as are of heptane gave 3-dodecylthiopropan-1,2 diol as a white indicated in the following claims. solid. Yield: 105.6 g. m.p. 53-54 C. 50 What is claimed is: 0.38 g (1.3 m moles) of 3-dodecylthio-propane-1,2- 1. A method for the preparation of 1-phenyl-1,2-bis(- diol are heated for two hours at 100 C. with an excess phenylthio)ethane wherein thiophenol is heated at re flux temperature is benzene with zinc chloride and with of dodecyl mercaptan and 0.5g of zinc chloride. an oxygenated aromatic derivative selected from the Chromatographic separation on silica gel with ben group consisting of phenyl-1-hydroxyphenethyl sul zene yields, after evapration, 0.84 g (~ 100%) of 1,2,3- 55 phide, phenyl-2-hydroxyphenethylsulphide and styrene trisdodecylthiopropane, m.p. 32-35° C. oxide for a period of time sufficient to form 1-phenyl EXAMPLE 7 1,2-bis(phenylthio)ethane, and 1-phenyl-1,2-bis(phenyl thio)ethane is separated. 2 cc of 1-phenethylalcohol, 5 cc of thiophenol and 2. A method for the preparation of 1-phenyl-1,2-bis(- approximately 1 g of anhydrous zinc chloride are dis 60 phenylthio)ethane which comprises heating thiophenol solved in 30 cc of benzene and stirred at room tempera at reflux temperature in benzene with zinc chloride and ture overnight (~ 15 hours). with phenyl-1-hydroxy-phenethyl . Vapour phase chromatography (Vpc) indicates that 3. A method for the preparation of 1-phenyl-1,2-bis(- the alcohol is completely disappeared and phenyl-1- phenylthio)ethane which comprises heating thiophenol phenethylsulphide is formed instead. Only minor impu 65 at reflux temperature in benzene with zinc chloride and rities are detected by vpc and thin layer chromatogra with phenyl-2-hydroxy-phenethyl sulfide. phy. k k sk