2- isothiazolium chloride

Dihydro-1,3-thiazine derivatives (208) and (210) are prepared by the addition of alkyl propiolates to thioureas and dithiocarbamic acids respectively. In the latter case it is necessary to cyclize the initial products (209) with acetic anhydride (Scheme 96) (70AJC51). Ring expansion of isothiazolium chlorides (211) by the action of potassium cyanide provides a route to imine derivatives (212 Scheme 97) (79TL1281). 

A reaction of rather less general application, but one which produces valuable intermediates, is the treatment of dithiosalicylamide and its A-substituted derivatives with phosphorus pentachloride. Thus, A.A-diethyldithiosalicylamide (20) yields 3-chloro-2-ethyl-l,2-benz-isothiazolium chloride (21).14-16 This salt (21) is a versatile compound for example, heating it with diethylamine gives 3-diethylamino-l,2-benzisothiazole (22)16, treatment with base yields 2-ethyl-l,2-benzisothiazolinone (23), and reaction with ammonia, followed by hydrochloric acid, affords 3-ethylamino-l,2-benzisothiazole (24).14 This final reaction involves an interesting rearrangement which will be discussed in more detail in Sections II, C, 2 and II, C, 3. 

The reduction with sodium borohydride of isothiazole (418) gives rise to the thiazole derivative (419). Similar results are obtained when the same isothiazolium chloride is treated with triphenyl-phosphine in chloroform (Equation (86)) <93JHC929>. 

When the reaction was carried out in the absence of a tertiary amine, N-alkylation of the isothiazole 84 took place and the 2-(chloroacetyl)isothiazolium chloride 85 was precipitated by the addition of ether (85BSB149, Scheme 26). The treatment of... 

The 4-chloromethyl isothiazole 86, which could be obtained from the isothiazolyl carbinol by treatment with thionyl chloride, was very reactive towards nucleophilic reagents. Thus 4-chloromethylisothiazole 86 underwent a self-quaternization to form the 4-chloromethyl-3-methyl-2-(3-methylisothiazol-4-ylmethyl)isothiazolium chloride 87 (68JCS(C)611, Scheme 27). 

Reaction of 2-alkyl/aryl isothiazol-3(2//)-thiones 90 with various alkyl-halogenides gave the 3-iS -alkyl-substituted isothiazolium salts 25a,91 in good-to-very-good yields (70BSF3076, 73CJC3081, 93JHC929, Scheme 29). Several isothiazolium iodides 25a,91a-n, perchlorate 25a and chlorides 91o-v were also synthesized. The structure of 2-methyl-5-aryl-isothiazolium chloride 91q, isolated in 60% yield, was confirmed by X-ray analysis. The S-alkylated isothiazolium salts 25a,91 with yields and references are represented in Table 5. 

The 2,3-heterocyclic annulated isothiazolium chloride 199 was obtained by intramolecular quaternization of salt 198b in poor yield (79JOC1118, Scheme 70). 

The oxidation of isothiazolium chlorides 135 with hydrogen peroxide in acetic acid at room temperature gave the 1,2,3-thiadiazine 1-oxides 408a,b in 15-51% yield. They were also converted into 1,2,3-thiadiazine 1,1-dioxides 409a-c in 16-43% yield. The structure 408b was confirmed by X-ray diffraction (00SUL109, Scheme 137). 

Isothiazolium chlorides (108) undergo ring-expansion when treated with cyanide ion the product is a 1,3-thiazine (109), illustrating once again the lability of the N—S bond in isothiazolium salts. 

Alkyl-3-chloroisothiazolium chlorides (131) react with ammonia to give 3-alkyl-aminoisothiazoles (132) (80MI41700), but with amines give mixtures of isomeric isothiazolium salts (133 and 134 Scheme 20) (79JOC1118), compound (134) presumably being formed by a similar mechanism to compound (132). 2-Alkyl-3-chloro-l,2-benzisothiazolium salts... 

Reaction of some isothiazolium salts (9) with hydrogen sulfide leads to unstable compounds which have been described as bis(l, 2-dithiol-3-yl) sulfides (10). These compounds are converted into 1,2-dithiolium salts (11) by strong acids such as hydrogen chloride or iodide, or perchloric acid. ... 

Table 5. S-Alkylation of isothiazol-3(2.ff)-thiones 90 to 3-alkylthio-isothiazolium iodides 25a,91a-n and chlorides 91o-v...

For a comparative study of the rates of )V-methylation, see p. 344. Nucleophilic replacement of the halogeno-substituent in 2-ethyl-3-chloro-l,2-benziso-thiazolium chloride (52) by (thio)phenols readily yields quaternary isothiazolium... 

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