Isothiazolium salts, reaction with

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. ... 

The reaction of 3-phenacylthio- (347) and 5-phenacylthio-isothiazolium salts 350 with triethylamine afforded 3-phenacylidenisothiazole 349 (39%) and isothiazol-5-thione 352 (50%) by deprotonation of the exocyclic methylene group (85BSB149, Scheme 117). 

Reaction of the isothiazolium perchlorate (499) with the potassium salt of 3-ethoxy-3-oxo-propanoate (ethyl acetate anion equivalent) affords thiophene (502) probably via intermediates (500) and (501) (Scheme 104) <84CJC1580>. Some other aminothiophenes were prepared in this way in moderate to good yields. Reaction of the isothiazolium salt (503) with the sulfonium ylide (504) produces a mixture of thiophenes (506) and (507) (Scheme 105). A mechanism involving the initial formation of (505) was presented. 

From Isothiazolium Salts and Other Reactions. An interesting synthesis of benzo-TA is based on recyclization of chlorothiazolium salts 93 by the action of formamides. The quantitative yield of products depends on the formamide used and the reaction conditions. If R is a sterically encumbered group (Me2CH, Me3C, or Ph), benzo-TAs 94 are formed, while other formamides give isomers 95. With 1,2-dichlorobenzene, only the isomers 94 were obtained. The regioselectivity of this reaction was explained by the position of nucleophilic attack of the formamide (71CB3757) (Scheme 30). 

Isothiazolium salts have been reconverted to isothiazoles by dry distillation27 and by treatment with ammonia.145 The latter reaction incidentally confirms that isothiazoles are alkylated on the nitrogen and not the sulfur. Isothiazolium salts with a vacant 3-position have given 3-thiones on treatment with sulfur in pyridine [Eq. (16)].63,64... 

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. 

Deprotonation at C-5 occurs with organolithium compounds (see Section 3.05.5.8). Few reactions with radicals and carbenes are known (see Section 3.05.5.9). Isothiazolium salts are ring opened by... 

EtOH. The yields of 33 were between 35 and 50%. The alkylation of the isothiazole 33 gave the isothiazolium salts 34a,b in 90% yield (79BSF26, Scheme 9). By reaction of the perchlorates 34 with a base, the isothiazolium-4-oleates 35 were obtained (79BSF26, 80PS79). 

The treatment of 1,2-dithiolium salts 43 with methylamine gave 3-methyl-aminothiopropenones 44, which were oxidized by iodine to form the TV-methyl-isothiazolium salts 27a,45a, isolated as their perchlorates (73CJC3081). The yields of products were rather poor but the reaction is a very quick synthesis of TV-methyl-isothiazolium salts 27a,45a from the 1,2-dithiolium salts 43 (Scheme 12). 

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. 

Especially, 2-phenyl-4,5,6,7-tetrahydro-l,2-benz- (121) and 5-methyl-2,4-diphenyl-isothiazolium salts 62 (R = H, 4-MeO, 2-C1, 2,6-Cl2) were studied with the HPLC-MS(MS) method to monitor the oxidation of isothiazolium salts with H202/acetic acid (96%) (03CG147). The strongly acidic reaction mixture was separated on a RP-18 column without any sample pretreatment and included intermediates, which were identified by API-MS(MS)-techniques. The aim of this work was to establish the reaction mechanism using several N-functionalized salts. 

Chloro-2-methyl-isothiazolium salts 75k,m,q,r were converted with malonodi-nitrile to 2-alkyl-3-(dicyanomethylen)-2,3-dihydroisothiazoles 410a-d by a condensation reaction (77DEP2851023, 78USP4281136, Scheme 138). 

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