1.2- Dithiolium salts isothiazoles

Certain dithiolium salts have been reported by Leaver and Robertson to form isothiazoles on treatment with ammonia thus, 3,5-diphenyl-l,2-ditholium perchlorate (15) gives a 50% yield of 3,5-diphenylisothiazole (16). The method does not appear to be generally applicable, and the analogous 3-methyl-5-phenyl-l,2-dithiolium salt did not give an isothiazole. 

Dithiolium salts, particularly with aromatic substituents, readily form isothiazoles on treatment with ammonia58-62 and a mechanism (Scheme 21) has been proposed by Olofson et al. °... 

Rather surprisingly, the product of the reaction between the 3,4-diphenyl-l,2-dithiolium salt and ammonia in ethanol was found to contain 4,5-diphenyltrithione, but no isothiazole, although the reaction with phenylhydrazine gave a 95% yield of the corresponding pyrazole.46... 

Judging from these early results, it appears that the reaction of 1,2-dithiolium salts with ammonia offers an elegant synthesis of certain substituted isothiazoles that are difficult to obtain by other methods.98 The reaction of the unsubstituted 1,2-dithiolium salt with NH8, however, does not yield the parent isothiazole system. Moreover, in the case of the 3(5)-methyl salts, the abstraction of a methyl proton activated by the positive charge of the ring successfully competes with this reaction (Section II,B,4).14a... 

There are at present no detailed data available as to whether and to what extent the formation of isothiazoles from unsymmetrically monoaryl-substituted 1,2-dithiolium salts is stereoselective, or how the ratio of the isomera can be influenced by variation of the substitution. 

Nitrogen nucleophiles react at C(3) (C(5)) to form 1,2-dithioles. The further products of the reactions depend on the substitution pattern of the dithiolium ring, the actual nucleophile, and occasionally the reaction medium. Dithiolium salts with nonreplaceable substituents react with ammonia to form isothiazoles (38) and with primary or secondary amines to form aminothiones (39) (Scheme 2) <65JCS32, 80AHC(27)151>. 

Further examples have been given of the reaction of 1,2-dithiolium salts (both 3,4-dialkyl and 3,5-dialkyl) with ammonia to give isothiazoles, and the formation of ring-opened products, (45) and (46), from 3-aryl-l,2-dithiolium perchlorates and excess of dimethylamine has been reported. The reactions of 3-methylthio-l,2-dithiolium salts with amines continue to be of interest. With primary aliphatic amines, 5-aryl-3-methylthio-l,2-dithiolium iodides give j8-alkylaminodithioacrylates (47) and isothiazoline-3-thiones (48) as well as the demethylated compounds (l,2-dithiole-3-thiones). Similar products are obtained with secondary amines, except that the isothiazole derivatives are replaced by 3-dialkylamino-l,2-dithio-lium iodides (49), the n.m.r. spectra of which indicate restricted rotation... 

Ring-opening reactions of dithiolium salts with amines continue to receive attention. The behaviour of 3-styryl derivatives deuteriated in various positions/ and of 3-ethoxy-1,2-dithiolium salts/ has been studied. Further examples have been provided of the formation of isothiazoles and pyrazoles by the action of ammonia and hydrazine, respectively. 3,5-Di-isopropyl-l,2-dithiolium cations are deprotonated by aqueous ethanolic ammonia to give the dithiole (29). ... 

From, 2-Dithiolans Type C). The general synthesis of isothiazoles from 1,2-dithiolans (see Vol. 2, p. 563 Vol. 3, p. 543) by reaction with ammonia or amines continues to be exploited. 3-Ethoxy-l,2-dithiolium salts (1) are cleaved by primary amines to the linear thioesters (2), which are in turn convertible into... 

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