Isothiazole 3.5- dimethyl

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). 

In an attempt to prepare an isothiazolobenzodiazepine, ethyl 5-o-aminoanilino-3-methyl-isothiazole-4-carboxylate was treated with sodium methoxide, but the only reaction was transesterification to the methyl ester 76UC(B)394). Only the 5-ester group of dimethyl 3-methylisothiazole-4,5-dicarboxylate reacts with iV,iV -diphenylguanidine, as with the corresponding isoxazole compound, but the product could not be cyclized, even under drastic conditions. This is in marked constrast to the isoxazole compound which cyclized at room temperature (80JCS(P1)1667). 

Isothiazole-4,5-dicarboxylic acid, 3-phenyl-dimethyl ester synthesis, S, 150 Isothiazole-5-glyoxylic acid ethyl ester reduction, 6, 156 Isothiazole-4-mercurioacetate reactions, 6, 164 Isothiazole-5-mercurioacetate reactions, 6, 164 Isothiazoles, 6, I3I-I75 acidity, 6, 141 alkylation, 6, 148 aromaticity, S, 32 6, 144-145 basicity, 6, I4I biological activity, 6, 175 boiling points, 6, I43-I44, 144 bond fixation, 6, 145 bond orders, 6, I32-I34 calculated, 6, 133 bromination, S, 58 6, 147 charge densities, 6, 132-134 cycloaddition reactions, 6, 152 desulfurization, S, 75 6, 152 deuteration, S, 70... 

Thiophene-1-oxide and 1 -substituted thiophenium salts present reduced aromaticity.144 A variety of aromaticity criteria were used in order to assess which of the 1,1-dioxide isomers of thiophene, thiazole, isothiazole, and thiadiazole was the most delocalized (Scheme 46).145 The relative aromaticity of those molecules is determined by the proximity of the nitrogen atoms to the sulfur, which actually accounts for its ability to participate in a push-pull system with the oxygen atoms of the sulfone moiety. The relative aromaticity decreases in the series isothiazole-1,1-dioxide (97) > thiazole-1,1 -dioxide (98) > thiophene-1-dioxide (99) then, one has the series 1,2,5 -thiadiazole-1,1 -dioxide (100) > 1, 2,4-thiadiaz-ole-1,1-dioxide (101) > 1,2,3-thiadiazole-1,1 -dioxide (102) > 1,3,4-thiadiazole-l,1-dioxide (103) in the order of decreasing aromaticity. As 1,2,5-thiadiazole-1,1-dioxide (100) was not synthesized, the approximations used extrapolations of data obtained for its 3,4-dimethyl-substituted analogue 104 (Scheme 46). 

The meso-ionic l,3>2-oxathiazol-5-ones (169) show an interesting range of reactions with nucleophiles including ammonia, primary amines, and aqueous alkali. They also react with l,3-dipolarophiles, including dimethyl acetylenedicarboxylate and methyl propiolate, yielding isothiazoles (171) and carbon dioxide. 1,3-Dipolar cycloaddition reactions with alkenes such as styrene, dimethyl maleate, and methyl cinnamate also lead to isothiazoles (171) directly. BicycUc intermediates (cf. 136) were not isolable these cycloaddition reactions with alkenes giving isothiazoles involve an additional dehydrogenation step. 

Dihydro-4,5-dimethyl-3-(hydroperoxy)-2-[4-(methoxycarbonyl)phenyl]isothiazole 1,1-dioxide (AFUPOG) 1.461 1.417 106.6 97... 

Dithiolylium salts may be converted into pyrazoles, pyrazolium salts and isothiazoles (see Section 3.4.1.6.2.ii). For example, 3-phenyl-1,2-thiolylium salt (74) with hydrazine, methylhydrazine or phenylhydrazine yielded the corresponding pyrazoles (75). 3,4-Dimethyl-1,2-dithiolylium perchlorate (76) with ammonia gave 4,5-dimethylisothiazole (77). 

Treatment of the l//-pyrazolo[4,3-isothiazole derivative (34) with dimethyl sulfate yielded the corresponding salt (35) in good yield (85KGS223). 

For example, thermolysis of (177) in the presence of DMAD resulted in formation of the dimethyl isothiazoledicarboxylate (182) (>90% yield). Benzonitrile sulfides, generated by the rare 1,3-elimination of two equivalents of hydrogen fluoride from (179), reacted with maleic anhydride (MA) to give dihydrofuro[3,4-d]isothiazole-4,6-diones (183 X = O). 

Substituent l-Methyl- pyrazole 1-Melhyl- pyrazolium Isoxazole Isothiazole 1,2-Dimethyl- pyrazolium... 

Methyl- and 3,5-dimethyl-isothiazole have been prepared from the appropriate isothiazol-5-yUithium compounds and methyl iodide. "... 

Reaction of a 3-aryl-l,2-dithiolium cation with phenylhydrazine gives a mixture of pyrazoles. Similarly, with a 4-aryl-l,2-dithiolium ion, 1,2-dimethyl- or 1,2-diphenylhydrazine give a pyrazolium ion. With hydroxylamine poor yields of mixtures of isoxazoles and isothiazoles are obtained. 

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