Benzisothiazoles, isothiazoles from

There are two series of benzisothiazoles, derived from benz[c]iso-thiazole (2) and benz[d]isothiazole (3), and both, if the benzene ring were suitable weakened, could doubtless be oxidized to isothiazole-dicarboxylic acids. In their first synthesis Adams and Slack... 

The exoeyelie earbonyl group of isothiazol-3-ones absorbs in the region 1610-1660 em <7lJHC59l). 2-Methylisothiazol-3-one itself has the C=0 and C=C bands at 1660 and 1629 em respeetively, in CCI4 solution <64TL1477). The low earbonyl frequeney is due in part to eontributions from the resonanee form (20b). The earbonyl frequeney inereases in sulfoxides (1660-1730 em ) and 1,1-dioxides (1690-1740 em ) where sueh forms are not favourable. Sulfoxides (1060-1190 em ) and sulfones (1330-1360 and 1150-1190 em ) absorb in the regions expeeted (e.g. saeeharin, 1353 and 1162 em ), but resonanee forms related to (13) eause a reduetion of the frequeney of the asymmetrie SO2 vibration to near 1280 em (70CB3166). A similar situation arises in 3-amino-1,2-benzisothiazole 1-oxides. 

There are many references in the patent literature to azo dyes prepared from 4- and 5-aminoisothiazoles, 3-, 5- and 7-amino-1,2-benzisothiazoles, and their quaternized derivatives. These are particularly useful in the dyeing of synthetic fibres. Isothiazole compounds have also been suggested for other industrial purposes, such as corrosion inhibitors, fireproofing agents, additives in rubber vulcanization, photographic chemicals and fluorescent whiteners in detergents. 

Thieno[3,4-d ]isothiazole-4-carboxylic acid synthesis, 6, 1023 Thienoisothiazoles benzisothiazoles from, 6, 172 Thieno[3,4-c]isothiazoles reactions, 6, 1034 synthesis, 6, 1043... 

A unique example is found in 2,1-benzisoxazole (40), which undergoes N-methylation 1.9 times faster than isoxazole (37).122 This is the only known example of rate acceleration resulting from benzo-fusion. Other interesting comparisons involve 2,1,3-benzoxadiazole (benzofurazan, 41), and 1,2,5-oxadiazole (furazan, 42),123 and also isothiazole (37), and 2,1-benzisothiazole (40).122 For these two pairs essentially no change in reactivity results when the azole is converted into its benzolog. 

Few other reactions of simple 1,2-benzisothiazoles have been described in the literature. There is, for example, no report of the formation of a quaternary salt directly from the parent compound. The isothiazole ring is generally quite stable to oxidation or reduction ... 

Isothiazoles and benzisothiazoles were described in the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I) <84CHEC-i(6)i3i>. The present work summarizes and augments, where appropriate, information from the first edition, but concentrates very much on literature published since 1982. Wherever possible, information is arranged in a similar format to that used in the first edition to facilitate comparisons. The chemistry of isothiazoles is regularly reviewed in Progress in Heterocyclic Chemistry, and specific subjects are discussed occasionally in Advances in Heterocyclic Chemistry, for example benzisothiazoles <85AHC(38)105> and aromaticity <93AHC(56)303>. 

The signals from the carbons of the benzene ring of 1,2-benzisothiazole absorb in the region of 120-135 ppm. Their assignments can be made on the basis of prediction from substituent effects, but should be made with more certainty from multiplicity and from two-dimensional NMR experiments which give unequivocal information from spin couplings. The heterocyclic part of the molecule can be considered to a first approximation as a 4,5-dialkyl-substituted isothiazole. Some typical C... 

Isothiazole and the benzisothiazoles are planar molecules, and the 1,1-dioxides, saccharin and thiosaccharin, and their salts, are all planar, apart, of course, from the oxygen atoms on sulfur. Calculations on isothiazole-1-oxide show that the heterocyclic ring has an envelope conformation, with the sulfur atom 22 pm above, and the oxygen atom 85 pm below, the plane of the other four atoms of the ring. This, of course, would result in a significant dipole moment, calculated to be 1.27 D, perpendicular to the plane of the ring <92JP074>. 

A series of compounds with a 2,1-benzisothiazol-basis were easily available from 2, 1-benzisothiazol-3(2//)-one 180. The treatment of 1-methyl-2, l-benzisothiazol-3 (2//)-one 180 with phosphorus pentasulfide in pyridine gave the 1-methyl 2,1-benz-isothiazol-3(2//)-thione 181 in 28% yield. The preparation of l-methyl-3-methylthio-... 

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