Isothiazole-5 -thiones, reaction

The reaction of 2,5-dimethylisoxazoline-3-thione with 48% HBr produced, among other products, an isothiazole-3-thione, diisoxazole disulfide and 2,5-dimethylisoxazolin-3-one. In contrast, the reaction of 2-methyl-5-phenylisoxazoline-3-thione produced primarily disulfide 80CPB487). The reaction with H2S in 48% HBr produced an isothiazole-3-thione and a cyclic thiazole (Scheme 75) (80CPB487). 

Few isothiazoles undergo simple cycloaddition reactions. 4-Nitroisothiazoles add to alkynes (see Section 4.17.7.4). With 5-thiones (84) and dimethyl acetylenedicarboxylate, addition to both sulfur atoms leads to 1,3-dithioles (85) (77SST(4)339, 80H(14)785, 81H(16)156, 81H(16)595). Isothiazol-3-one 1-oxide and the corresponding 1,1-dioxide give normal adducts with cyclopentadiene and anthracene (80MI41700), and saccharin forms simple 1 1 or 1 2 adducts with dimethyl acetylenedicarboxylate (72IJC(B)881). 

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... 

Thiete structures have been suggested as fragmentation products in the mass spectra of a thietane fused to a 3-lactam, an ortho disulfide of a thiolbenzoate ester, -propanethiol, thiirane carboxylic acid esters, isothiazoles, thiazoles, 1,3-dithiole 2-thiones, 1,3-dithiolene-2-ones, S-ethyl thio-benzoate, and thianaphthene sulfones. Tetramethylthiete may have been formed on thermolysis of the p-toluenesulfonyl-hydrazone of 2,2,4,4-tetramethyl-3-thietanone. " Thiete 2-thione may be an intermediate in the decomposition of 1,2-ditholium salts by the action of bases. " 2,2-Diphenyl-2H-thiete is suggested as an intermediate in the reaction of diphenyldiazomethane with 1,2,3-benzo-thiadiazole which yields 9-phenylthioxanthene and three other products. ... 

Space group and unit cell dimensions are given for 4,5-diphenyl-l,2-dithiole-3-thione.266 The reaction product from 1,2-benzodithiolethione and hydroxylamine was originally ascribed the isothiazole structure 175.267 However, X-ray structure studies have shown it to be 1,2-benzodithiolone oxime. (176).268... 

Isothiazoles are reported to yield the lactam (101) on reaction with diphenyl ketene <85BSB149>. Ethyne dicarboxylate esters add to 2,1-benzisothiazole to generate quinoline esters (102), and benzyne reacts to yield aeridine <83H(20)489, 88JCS(Pl)2l4l>. 2-Methyl-2,l-benzisothiazolin-3-thione with acetylene esters forms 2-iminobenzoquinone methides (103), which dimerize to give diazocines (104) or further react with the ethyne ester to yield diadducts (105). The initial adduct formed with phenylethyne and 2-methyl-2,l-benzisothiazolin-3-thione rearranges to produce l,2-dithiole[3,26]... 

A one-pot synthesis of 4-substituted isothiazoles from I-acyl alkynes is described where sulfur is added as the last atom fragment (Scheme 27) <87H(26)1587,89H(29)97>. The reaction of ketones with carbon disulfide, sulfur, and ammonium hydroxide followed by treatment with acid gives the 3,4-dialkyl-substituted isothiazolin-5-thiones (Scheme 27) <79JCR(S)4I0,88BCJ4443>. 

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 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). 

IR spectra, 6, 142 synthesis, 5, 135, 156 6, 166-173 tautomerism, 6, 145-146 thermolysis, 6, 144 toxicity, 1, 138 UV spectra, 6, 140 Vilsmeier-Haack formylation, 6, 154 X-ray diffraction, 6, 134-136 Isothiazole-3-thiol, 5-phenyl-tautomerism, 6, 146 Isothiazole-3-thione, 2-alkyl-,3C NMR, 6, 138 Isothiazole-5-thione, 2-alkyl-13C NMR, 6, 138 Isothiazole-5-thione, 2,4-diphenyl-reaction... 

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... 

Condensation of Nitriles and Dialkyl Sulphites. (Type C).—A novel isothiazole synthesis involves the interaction of phenylacetonitrile anion, generated in the presence of sodamide, and diethyl sulphite. The main product of the reaction, 4,5-diphenylisothiazol-3-ol (17) (47%), is accompanied by a-cyano-a-(4,5-diphenylisothiazol-3-yl)benzyl phenyl thione (18) (up to 15%). The use of other dialkyl sulphites produces the same isothiazolol (17), but in much reduced yields (9—18%). The reaction may possibly proceed by way of the sulphine intermediate (15), as outlined in Scheme 1, terminating with loss of hydrogen cyanide from (16). ... 

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