Sulfoxides from thionyl chloride

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Di(l-alkynyl)sulfides are formed in excellent yields, if (freshly distilled) sulfur dichloride is added to a solution or suspension of a lithium alkynylide in Et20 [106). In an analogous manner, di(l-alkynyl)sulfoxides are formed from thionyl chloride and an alkynyllithium [106], while sulfinyl chlorides R S(=0)G may be used to prepare the sulfoxides RC=CS(=0)R Preliminary experiments suggest that interaction between alkynyllithium and sulfonyl chlorides R S02C1 can give both sulfones ROCSOjR and chlofo-alkynes RCsCCl [2). 

Treatment of pyridyl carbinol 51 with thionyl chloride leads to the corresponding chloride (52), Treatment of that intermediate with 5-methoxy-2-mercaptobenzimidazole (53), obtained from reaction of 4-methoxy-q-phenylenediamine with potassium ethylxanthate leads to displacement of halogen and formation of the sulfide (54). Finally, oxidation with 3-chloroperbenzoic acid produces the sulfoxide omeprazole (55) fl7]. 

The facile synthesis of bis(l,2,4-triazolyl)sulfoxide 47 was achieved from the reaction of 1-trimethylsilyl-l,2,4-triazole 46 with thionyl chloride (Equation 13). This compound was then used as a triazole-donor reagent in the synthesis of l,l-bis(l,2,4-triazolyl) derivatives of carbonyl compounds <2000JHC743>. 

Another example that illustrates formation of a disulfonium dication as an intermediate was found in the reaction of sulfoxide 13 and thionyl chloride. Instead of the normal a-chlorosulfide Pummerer product, the reaction leads to a stable chlorosulfonium salt 66.89 Hydrolysis of the salt obtained from 2,2,8,8-tetradeuteriated sulfoxide 37 results in a 1 1 mixture of the two possible isomers, thus indicating that the chlorosulfonium salt does exist in rapid equilibrium with a symmetric S-S dication (Scheme 24). 

The action of phosphorus halides on pyrrolinones and related compounds offers an alternative route to chloropyrroles. Yields of around 60% of 2,5-dichloropyrroles were obtained in this way from N-substituted succinimides (82ZC126). Vilsmeier reaction of N-alkylsuccinimidals formed chlorinated pyrrole aldehydes in modest yields (90CJC791), and there are other examples [66YZ158 81H(15)547]. A useful synthesis of chloropyrrole-2-carboxylates employed the action of phosphorus pentachloride on pyrrolidin-2-one-5-carboxylates (40) (87CB45) (Scheme 15), and in a Pummerer-type reaction pyrrol-3-yl sulfoxides were transformed by thionyl chloride into chloropyrroles. Yields were increased to >80% by the use of oxalyl chloride (88JOC2634) (Scheme 15). 

When /3-vinylbutenolide (158), prepared from /3-vinylbutyrolactone by a sulfenylation-sulfoxide elimination process, was reacted with the anion of a-methylcyclohexane-1,3-dione, two products (159) and (160) were produced in an 11 1 ratio (47% combined yield) (75CC337). Dehydration of these compounds with thionyl chloride in pyridine yielded (161) and (162), respectively (Scheme 35). The annelation products are useful intermediates for sesquiterpene lactone construction. 

Treatment of the sulfoxide prepared from p-cresol and thionyl chloride with a mixture of TFAA and KHCO3 in acetonitrile at -30°C led to formation of an orthoquinone mono(monothioketal). Desulfurisation with NiCl2(PPh3)2 gave 2-(4-methylphenoxy)-4-methylphenol in 38% overall yield. 

Starting from pyridazine 144, n-phenyl thiazepine 211 can be synthesized. The conversion of the hydroxy group of 144 to chloride 210 with thionyl chloride, followed by ring closure with sodium sulfide monohydrate in dimethyl sulfoxide (DMSO), yielded the desired thiazepine 95 (Scheme 37) <1996JHC583>. 

Preparation of Di(I-alkynyl)sulfides and Di(l-alkynyI)sulfoxides from Aikvnyllithium and Sulfur Dichloride or Thionyl Chloride... 

The use of aminosulfites in the synthesis of o.p. sulfoxides was described for the first time in 1973 by Wudl and Lee,98 using ephedrine as chiral auxiliary. In 1991, Benson and Snyder reported a modification of the Wudl and Lee procedure, obtaining o.p. sulfoxides in high yield by sequential displacement reactions of organometallic reagents on the 1,2,3-oxathiazolidine-S-oxide (aminosulfite 70), obtained from ephedrine and thionyl chloride.99... 

The previous reaction describes the synthesis of a novel class of heterocycles by the name of [l,2,3]thiadiazolo[4,5- /]-pyrimidines. Visibly, a redox process is involved, whereby the initial hydrazine derivative becomes an R-N=N-R system and, at the same time, the sulfur atom in thionyl chloride is converted to an azo-sulfide. The transfer of oxidaton level from sulfur—as sulfoxide—to the neighboring atom is a well documented process in sulfur chemistry that is called the Pummerer rearrangement. In essence, it involves the treatment of sulfoxides with an electrophile such as acetic anhydride to yield an a-acetoxy sulfide, according to the following sequence (see Scheme 26.1) ... 

The reaction of sulfoxide (147) with thionyl chloride, which produces a,p-dichlorosulfides (148 Y = W = Cl) in 85-95% yields, is an example of pathway 1. Illustrating pathway 2 is the remarkable enantiospecific formation of lactone (150) from the reaction of dichloroketene with the chiral sulfoxide (149 equation 28). ° ... 

Synthesis of aromatic sulfoxides is usually effected preparatively by one of the two following methods. First, aromatic compounds can be treated with thionyl chloride under Friedel-Crafts conditions di-p-tolyl sulfoxide has thus been obtained from toluene,232 diphenyl sulfoxide from benzene,233,234 and bis-Q -hydroxyphenyl) sulfoxide from phenol.235... 

Diphenyl sulfoxide Finely powdered aluminum chloride (30 g) is added in portions to benzene (50 g) and thionyl chloride (16 g) cooled in cold water. Then more benzene (20 g) is added and the whole is heated for 30 min on a water-bath, cooled, and poured into water. The benzene layer, when separated, washed, dried, and evaporated, provides diphenyl sulfoxide (21 g), which after recrystallization from light petroleum has m.p. 70-71°. 

A novel, mild method for the preparation of diaryl sulfoxides from arenes and thionyl chloride has been developed in TfOH medium. Under the nonoxidative reaction conditions only sulfoxides are produced without any contamination from the corresponding sulfones (eq 43). ... 

Other Applications. Thionyl chloride has been used to convert epoxides to vicinal dichlorides and for the preparation of dialkyl sulfides from Grignard reagents. Phenols react with SOCI2 to produce aryl chlorosulfites and diaryl sulfites or nuclear substitution products. As shown in eq 14, Aluminum Chloride catalysis yields symmetric sulfoxides, while in the absence of Lewis acids, aromatic thiosulfonates are the principal products. Primary amines, especially aromatic ones, react with SOCI2 to produce N-sulfiny lamines, which are potent enophiles and useful precursors to some heterocyclic compounds. ... 

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