Thionyl chloride reaction with sulfoxides

The sulfoxide (137, Scheme 2.22) is readily available following a short sequence of reactions that initiates with conversion of (/ )-phenylglycine methyl ester HCl into N-Tosyl alcohol 135. Cyclization with thionyl chloride 136 gives sulfoxide 137 (99% ee) ... 

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). 

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]. 

In absence of diluent or other effective control of reaction rate, the sulfoxide reacts violently or explosively with the following acetyl chloride, benzenesul-fonyl chloride, cyanuric chloride, phosphorus trichloride, phosphoryl chloride, tetrachlorosilane, sulfur dichloride, disulfur dichloride, sulfuryl chloride or thionyl chloride [1], These violent reactions are explained in terms of exothermic polymerisation of formaldehyde produced under a variety of conditions by interaction of the sulfoxide with reactive halides, acidic or basic reagents [2], Oxalyl chloride reacts explosively with DMSO at ambient temperature, but controllably in dichloromethane at -60°C [3]. 

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>. 

The Hurd-Mori reaction,where a tosylhydrazone is converted by thionyl chloride to the corresponding thiadiazole, involves the formation of a 1,2,3-thiadiazole-3,3-dioxide. In one example, this type of compound was isolated and subsequently deoxygenated with thiourea <1991PS175>. There have been no further reports of S-linked sulfoxide or sulfone derivatives of 1,2,3-thiadiazoles since the publication of CHEC-II(1996). 

The synthesis of the benzoimidazo[l,2- ][l,2,3]thiadiazole 61 can be explained using the same mechanistic model to that used for the Hurd-Mori reaction. The amino benzimidazole 58 when treated with thionyl chloride at reflux affords the benzoimidazo[l,2-r ][l,2,3]thiadiazole 61. If, however, the reactant 58 is treated with thionyl chloride at room temperature, the chloromethyl derivative 59 is formed. This derivative was then transformed into product 61 on reflux with thionyl chloride. The proposed mechanism for the formation of product 61 is for the initial formation of the sulfoxide 60, which then undergoes a Pummerer-like rearrangement, followed by loss of SO2 and HC1 to give the c-fused 1,2,3-thiadiazole 61 (Scheme 7) <2003TL6635>. 

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). 

An unsuccessful attempt to repeat this reaction was made by Bird however, he was able to show that dibenzothiophene 5-oxide did, in fact, react with either thionyl chloride or phosphorus oxychloride to yield 2-chlorodibenzothiophene in good yield. Since all methods of nitration of dibenzothiophene yield a mixture of 2-nitrodibenzothio-phene and dibenzothiophene 5-oxide, which have identical melting points, it was concluded that the earlier workers had in fact been working with the sulfoxide and not the nitro compound. The reaction was rationalized as being a deoxygenative halogenation of a heterocyclic 5-oxide akin to the Meisenheimer reaction of A-oxides, which already had precedents in the sulfoxide field. Unfortunately the 2-chlorodibenzothiophene prepared by this route is contaminated with 2,8-dichlorodibenzothiophene which cannot be removed by crystallization. The best method of preparation of this compound is therefore via a Sandmeyer reaction on 2-aminodibenzothiophene. ... 

The 5-unsubstituted-l,2,3-triazol-4-ones (176, R = H) participate in electrophilic substitution reactions. Bromination in chloroform of anhydro-4-hydroxy-l,3-dimethyl-1,2,3-triazolium hydroxide (180) gave its 5-bromo derivative (182). The meso-ionic 3-aryl-1,2,3-triazol-4-ones (176, R = Me, R = Ar, R = H) gave 5-bromo derivatives (176, R = Me, R = Ar, R = Br) with bromine in acetic acid. Their reaction with sulphur monochloride gave the sulfide (189, X = S), and with thionyl chloride they gave the sulfoxide (189, X = SO). ... 

The known dibromide 464 was converted in good yield to the dinitrile 465 by reaction with buffered potassium or sodium cyanide. Reaction of 2,5-dimethoxycarbonyl-3,4-dicyanomethylthiophene 465 with thionyl chloride and selenium oxychloride gave thieno[3,4-f]thiophene 466 and selenolo[3,4-f]thiophene 467, respectively (Scheme 57) <2002JOC2453>. In the case of thionyl chloride as the sulfur transfer reagent, an intermediate sulfoxide 468 must be involved, which then suffers a spontaneous base-catalyzed Pummerer reaction to give 466 in high yield. 

To 1.17 g of (-)-7,8-difluoro-2,3-dihydro-3-hydroxymethyl-4H-[l,4] benzoxazine was added 2.77 g of thionyl chloride in pyridine. The reaction mixture was concentrated and the concentrate was subjected to column chromatography using 40 g of silica gel and eluted with chloroform to obtain 1.18 g of the reaction product as a colorless oily product. This product was dissolved in 30 ml of dimethyl sulfoxide, and 0.41 g of sodium borohydride was added thereto, followed by heating at 80-90°C for 1 hour. The reaction mixture was dissolved in 500 ml of benzene, washed with water to remove the dimethyl sulfoxide, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The concentrate was subjected to column chromatography using 40 g of silica gel and eluted with benzene to obtain 0.80 g of (-)-7,8-difluoro-2,3-dihydro-3-methyl-4H-[l,4]benzoxazine as a colorless oily product [a]D25 = -9.6° (c = 2.17, CHCI3). Optical Purity >99% e.e. 

Benzo[f]thiophene 710 is prepared by the dehydration of sulfoxide 709 with KOBu as a variant method of the Pummerer reaction. Irradiation of 710 affords 711 as a first example of Dewar benzo[dthiophene (Scheme 108) <1995TL3177>. Reaction of dinitrile 712 with thionyl chloride in the presence of EtsN yields thieno[3,4-dthio-phene 714 via Pummerer dehydration of the intermediate 713 <2000TL8843, 2002JOC2453>. 

As with trifluoroacetic anhydride, activation of dimethyl sulfoxide with thionyl chloride must be carried out at low temperatures as the reaction is highly exothenmic. Besides the higher yields, a further advantage of thionyl chloride to activate dimethyl sulfoxide over anhydrides is the lack of Pummerer rearrangement products or of esters formed as by-products (as long as Ae reactions are carried out below -60 C). This is amply demonstrated by the oxidation of (-)-bomeol which proceeds in an excellent 99% yield (equation 12). ... 

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) ... 

Diaryl sulfoxides can be prepared by the reaction of aromatic compounds with thionyl chloride and triflic acid. Diaryl sulfones have also been prepared using... 

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). ° ... 

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