Isothiazoles, alkyl

Beckmann rearrangement, 6, 156 Isothiazole, 3-alkoxy-tautomerism, 6, 145 Isothiazole, alkyl-bromination, 5, 58 Isothiazole, 3-alkyl-5-amino-synthesis, 6, 166 Isothiazole, alkylthio-mass spectra, 6, 142 Isothiazole, amino-azo dyes from, 1, 330 tautomerism, 6, 157 Isothiazole, 3-amino-synthesis, 5, 135 tautomerism, 6, 146 Isothiazole, 4-amino-azo dyes from, 6, 175 diazotization, 6, 158 methylation, 5, 95 quaternization, 6, 158 reactions... 

Alkyl- and arylthiazoles rearrange undernltraviolel irradiation in different solvents to yield the corresponding isothiazoles or isomeric thiazoles. With alkylthiazoles the overall yields are very low, and it is not possible to use this method preparatively. For arylthiazoles it is possible 2-arylthiazoles. for instance, can be used to prepare 3-arylisothiazoles that are otherwise very difficult to obtain. 

Isothiazoles and isothiazolium cations are attacked by carbanions at sulfur and on recyclization can give thiophenes, illustrated by (147) -> (148). 2-Alkyl-3-isothiazolinones e.g. 149) are also vulnerable to nucleophilic attack at sulfur (72AHC 14)1). 

Pyrazoles, isoxazoles and isothiazoles with a hydroxyl group in the 3-position (491 Z = NR, O, S) could isomerize to 3-azolinones (492). However, these compounds behave as true hydroxy derivatives and show phenolic properties. They give an intense violet color with iron(III) chloride and form a salt (493) with sodium hydroxide which can be O-alkylated by alkyl halides (to give 494 R = alkyl) and acylated by acid chlorides (to give 494 R = acyl). 

Alkyl-5-acetamidoisothiazoles are nitrosated at the 4-position by nitrosylsulfuric acid (78JOC4154). Isothiazoles are sulfonated at the 4-position using either oleum or sulfur trioxide <72AHQ14)1). 

One of the best methods of synthesis of isothiazoles is by direct oxidation of y- iminothiols (169) or their tautomers. The reaction is capable of many ramifications and is represented by the general equation shown in Scheme 27. The substituents represent a wide range of groups. Thus, iminothioamides (169 R = NH2) are oxidized to give 3-alkyl-5-aminoisothiazoles (170 = NH2), amidines (169 R = NH2) produce 3-amino compounds,... 

Isothiazole, 5-acetamido-3-alkyl-nitrosation, 5, 59 6, 148 Isothiazole, 5-acetyl-thiosemicarbazone biological activity, 6, 175 Isothiazole, 4-acetyl-5-amino-3-bromo-synthesis, 6, 166 Isothiazole, 4-acetyl-3-methyl-oxime... 

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... 

Isothiazole, like its simple alkyl derivatives, is a mobile, colorless liquid, 6 1.1706, 1.5320, b.p. 114°, with an odor resembling... 

A novel synthesis of alkylsulfanylisothiazoles 230 starts with sodium a-cyanoketene dithiolates 227, obtained by the reaction of cyanoacetamides 226 with carbon disulfide in the presence of sodium ethoxide <06SC825>. Treatment of 227 with sulphur and piperidine acetate generates sodium isothiazole-3,5-dithiolates 229. The formation of 229 is assumed to arise from the addition of anionic sulphur to the nitrile group in 227 to give the intermediate 228, which cyclizes upon elimination of anionic sulphur to yield 229. Salts 229 are readily alkylated to furnish 3,5-bis(alkylthio)isothiazole derivatives 230. 

The standard means for preparing oxicams 285, initially developed by Lombardino, is through the base-promoted rearrangement reaction of isothiazole dioxides 286, which in turn are prepared from saccharin derivatives such as 287 (Scheme 40) <1981AHC(28)73>. The oxicam core can be further derivatized by N-alkylation of oxicam 285 and amidation of the C-3 ester functionality of 288 to form the common drug scaffold 289. 

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