Isothiazoles thioamides

Simple isothiazole-4-carboxylic acids have been made from the corresponding nitriles, which are available in turn from the halogeno derivatives, or directly by the olefin route.5-Aminoiso-thiazole-4-esters and -nitriles are readily obtained by the thioamide route. The 4-acids behave normally and form acid chlorides, esters, amides, and hydrazides. In contrast to the 5-series... 

Isothiazole synthesis Isothiazole can be prepared from thioamide in the following way. 

Pyrazolo[3,4-c]furazans (71) have been prepared by dehydration of dioximinopyrazolines 70,70 and fused isothiazoles 73 by oxidative cyclization of thioamides 727 following adaptations of standard syntheses of furazans and isothiazoles. 

Isothiazoles are usually prepared by routes involving formation of the nitrogen—sulphur bond in the cyclisation step. This is often set up by oxidation of the sulphur atom, as in the conversion of thioamide 4.29 to isothiazole 4.30. 

Synthesis of Isothiazoles from Aqueous Ammonia and Thioamide Vinylogues (Type H). Aqueous ammonia transaminates the thioamide vinylogues. In addition, the 3-amino-l-arylpropenethiones, in the presence of elemental sulphur, undergo ring-closure to give 65-95% of 5-arylisothiazoles (9) (Scheme 2). 

Moreover, Shibasaki developed a direct catalytic enantioselective conjugate addition of allyl cyanide 37 to a,(3-unsaturated thioamides (Scheme 2.25). A sequential Cu(i)-catalysed intramolecular cyclisation gave rise to enantioenriched fused isothiazoles 41 via Z-olefins 40. 

The hydrogen peroxide oxidation of N-(ethoxycarbonyl)pyrrole-2-thio-carboxamide (225) has been the subject of a recent study by Papadopoulos, who found that in basic media (225) is converted into the corresponding amide, whereas in acidic solution the sulphine (271) is formed. The thiocarbonyl group in (272) [the cyclization product obtained by heating (225) in quinoline] behaved similarly. Several examples of the formation of heterocyclic compounds, especially isothiazole derivatives, by oxidative treatment of appropriate thioamides have appeared. The... 

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