NEW SYNTHESIS OF ISOTHIAZOLES FROM PRIMARY ENAMINES

Methyl 3-aminocrotonate 7 reacts with 4,5-dichloro-1,2,3-dithiazolium chloride 1 at room temperature to give methyl 5-cyano-3-methylisothiaz ole-4-carboxylate 9 in high yield (78%) (Schemes 1 and 2). This reacti on is formally related to Woodward's synthesis of methyl 3-methylisoth iazole-4-carboxylate 24 from the same enamine and thiophosgene (Scheme 7). 3-Aminocrotononitrile 10 is similarly converted into 4,5-dicyano- 3-methylisothiazole 12 but the yield is much reduced (to 40%) since th e reaction is more complex (Scheme 3) giving 2,3,5-tricyano-4,6-dimeth ylpyridine 14 (20%), in a new pyridine ring construction, and three ot her minor products. All the products can be accounted for by reasonabl e mechanisms (Schemes 4, 5 and 6). One of the minor products, ketone 1 3, has been synthesized from the enolate anion 21 and the reagent 1, a nd the analogous ketones 23 have been readily prepared in high yield f rom the active methylene compounds 22 and reagent 1.