Dialkyl thioethers

The profitable conversion of thiouronium salts into dialkyl thioethers (see Section 4.1) is less successful for synthesis of diaryl thioethers. For example, l-chloro-4-nitrobenzene reacts with bis-thiouronium salts of the type (H2N)2CS(CH2) SC(NH2)2+ under soliddiquid and liquidrliquid conditions to produce the desired bis-thioethers, ArS(CH2) SAr, (20-35%), together with the diaryl sulphide, Ar2S (5-15%). Higher yields of the diaryl sulphide are observed under liquiddiquid conditions whereas, under solidiliquid conditions, the diaryl disulphide, (ArS)2, (20%) is also formed [56], Diaryl disulphides are the sole products (>65%) from the stoichiometric reaction of aryl diazonium salts with benzyltriethylammonium tetrathiomolybdate [57],... 

In contrast with the reactions involving sulphide or hydrogen sulphide anions, aryl alkyl thioethers and unsymmetrical dialkyl thioethers (Table 4.3) are obtained conveniently by the analogous nucleophilic substitution reactions between haloalkanes and aryl or alkylthiols under mildly basic conditions in the presence of a quaternary ammonium salt [9-15] or polymer-supported quaternary ammonium salt [16]. Dimethyl carbonate is a very effective agent in the formation of methyl thioethers (4.1.4.B) [17]. 

A superior and relatively versatile procedure for the synthesis of unsymmetrical dialkyl thioethers, which avoids the unattractive direct use of thiols, utilizes the stable l-alkylthioethaniminium halides, which are readily obtained from thioacet-amidc [32] (Scheme 4.4). The reaction has also been used for the synthesis of alkyl aryl thioethers from activated aryl halides [33], but it cannot be used for the synthesis of cyclic thioethers, as polymeric sulphides are formed from a,co-dihaloalkanes. A similar sequence to that which leads to the thioethers has been used for the synthesis of S-alkyl thioesters [34] (see 4.1.26). 

Synthesis of unsymmetrical dialkyl thioethers from 1-alkylthio-ethaniminium halides (Table 4.7)... 

A procedure, which has been used successfully for the synthesis of dialkyl thioethers from thioacetamide has been extended to the preparation of a range of 5-alkyl thiocarboxylic esters [35] (Table 4.20). The intermediate 5-acyl ethaniminium salt (Scheme 4.14) is not stable and is converted directly into the 5-alkyl thioester. The choice of catalyst affects the yield of the thioesters. Thus, 5-n-octyl thiobenzoate... 

The reactivity of thiepane (35) is generally similar to other dialkyl thioethers where the sulfur atom provides the major site for chemical transformation. The thiepane seven-membered ring system is of particular interest however since it can undergo transannular reactions and can form cycloalkyne derivatives. 

Cleavage of thioethers. von Braun found that a dialkyl thioether is cleaved by cyanogen bromide at a somewhat elevated temperature (60-70°, sealed tube) to an alkyl thiocyanate and an alkyl bromide. Results for the first three mixed ethers disclose a clear relationship of Haftfestigkeit to size of group ... 

Interaction of trialkyl alanes with elementary sulfur in equimolar amounts gives dialkyl-alkylmercapto alanes in relatively good yield. Attempts to introduce more sulfur into the organoaluminum compound gave no well-defined products. Hydrolysis of these compounds produced, in addition to thiols, hydrogen sulfide, dialkyl thioethers, and compounds with a higher sulfur content (dialkyl dithio and trithio ethers) (114, 271). The products from the reaction of trialkyl alanes with selenium were of similar complexity (271). 

Replacement of Boron by Sulfur and Selenium. Trialkylboranes are cleaved by dialkyl- and diaryldisulfides in an air-catalyzed radical reaction producing mixed thioethers (259). 

Another approach in the use of chiral S/P ligands for the hydrosilylation reaction of ketones was proposed more recently by Evans et Thus, in 2003, these workers studied the application of new chiral thioether-phosphinite ligands to enantioselective rhodium-catalysed ketone hydrosilylation processes. For a wide variety of ketones, such as acyclic aryl alkyl and dialkyl ketones as well as cyclic aryl alkyl ketones and also cyclic keto esters, the reaction gave high levels of enantioselectivity of up to 99% ee (Scheme 10.44). 

No sulfoxide complexes of osmium have been reported. Unsymmetri-cal dialkyl sulfoxides have been utilized in extraction studies, and methyl-4,8-dimethylnonyl sulfoxide has found application in the extraction of iron (266). Extraction of ruthenium from hydrochloric acid solutions by sulfoxides has been studied (470) and comparisons of sul-fones, sulfoxides, and thioethers as extractants for nitrosoruthenium species reported (441, 443). Similar studies on the extraction of nitro-soosmium species have been reported (442). 

Powdered KOH (0.17 g, 3 mmol) is added to the freshly prepared thioiminium halide [MeC(SR)NH2+Cl- or McC(SR)NMc2+C1 ] (3 mmol) and TEBA-C1 (0.12 g, 0.5 mmol) in CH2C12 (30 ml). The mixture is stirred at room temperature until the reaction is complete, as shown by TLC analysis. The organic phase is separated, washed with H20 (2 x 25 ml), dried (Na2S04), and the solvent evaporated under reduced pressure to yield the alkyl aryl thioether and the dialkyl disulphide, which can be separated by chromatography from silica. 

An alternative procedure for the synthesis of unsymmetrical thioethers, which is equally versatile and also avoids the direct use of thiols, utilizes 0,5-dialkyl [35] or 5,5-dialkyl dithiocarbonates [36] (Scheme 4.5). 

In a one-pot synthesis of thioethers, starting from potassium 0-alkyl dithiocarbonate [36], the base hydrolyses of the intermediate dialkyl ester, and subsequent nucleophilic substitution reaction by the released thiolate anion upon the unhydrolysed 0,5-dialkyl ester produces the symmetrical thioether. Yields from the O-methyl ester tend to be poor, but are improved if cyclohexane is used as the solvent in the hydrolysis step (Table 4.13). In the alternative route from the 5,5-dialkyl dithiocarbonates, hydrolysis of the ester in the presence of an alkylating agent leads to the unsymmetrical thioether [39] (Table 4.14). The slow release of the thiolate anions in both reactions makes the procedure socially more acceptable and obviates losses by oxidation. 

Selected examples of unsymmetrical thioethers from 5,5-dialkyl dithiocarbonates... 

Method A The 0,5-dialkyl dithiocarbonate is prepared by procedure 4.1.14 from O-alkyl potassium dithiocarbonate (50 mmol). The mixture is cooled to 50 °C and, without isolation of the ester, KOH pellets (14 g, 0.25 mol) are added portionwise at <80 °C. The mixture is stirred at 80 °C until GLC analysis indicates the complete disappearance of the ester (ca. 30 min). Petroleum ether (b.p. 40-60 °C, 150 ml) is added and the organic phase is separated, dried (Na2S04), filtered through silica, and fractionally distilled to give the thioether. 

The haloalkane (20 mmol), 5,5-dialkyl dithiocarbonate (l I mmol) and TBA-Br (0.05 g, 0.15 mmol) in aqueous KOH (30%, 10 ml) are stirred under reflux (Table 4.14). The cooled mixture is extracted with Et20 (3 x 50 ml) and the combined extracts are washed with H20 (3 x 50 ml), dried (Na2S04), and evaporated under reduced pressure to yield the thioether. 

As indicated above, the traditional base-catalysed hydrolysis of 0,5-dialkyl thio-carbonates for the synthesis of thiols is generally unsatisfactory, as oxidation leads to the formation of disulphides. Under phase-transfer conditions, the procedure produces thioethers to the virtual exclusion of the thiols, as a result of the slow release of the thiolate anions in the presence of the electrophilic ester. However, a simple modification of the reaction conditions provides an efficient one-pot reaction [50] from haloalkanes (Table 4.15) via the intermediate formation of the thermally labile (9-/ert-butyl-5-alkyl dithiocarbonates (Scheme 4.8). 

In the reaction of the phenylacetonitrile carbanion with thiocyanates, a major side reaction leads to the formation of the dialkyl disulphides, as a result of the base-catalysed decomposition of the thiocyanate. This side reaction is reported to be insignificant in the reactions of the other carbanions. Phenylacetonitrile reacts with 1,2-ethanyl bisthiocyanate to produce 2-cyano-2-phenyl-1,3-thiolanes [52] under conditions analogous to those used for the synthesis of the thioethers (Scheme 4.12). 

Sulphoxides and sulphoximines are reduced to thioethers by similar reaction sequences [3, 4], In most cases, the yields of the thioethers are higher (>70%) from the diaryl compounds, than from dialkyl or aryl alkyl derivatives but, when the reductions are conducted in an excess of chloroform, the yields of the thioethers are diminished [3], This observation suggests that the thioethers are reacting with dichlorocarbene and that the dialkyl and aryl alkyl compounds are more susceptible than the diaryl derivatives (Table 11.20). 

Dialkyl and diaryl thioethers generally react with silver(I) salts to form 1 1 complexes.309,310 Few data are available for these adducts however, on the basis of formation constants they appear to have relatively high stability (Table 44).311,312... 

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