Ring Opening of Dihydro-1,4-oxathiins

Abstract

Acid hydrolysis of 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxanilide gives 2-(2-hydroxyethylthio)-acetoacetanilide enol. 3-Carbonyl-substituted 5,6-dihydro-1,4-oxathiins were found to undergo ring cleavage by nucleophilic nitrogen attack on C-2. Thus the following reactions were observed: 3-acetyl-5,6-dihydro-2-methyl-1,4-oxathiin on treatment with hydrazine gives 4-(2-hydroxyethylthio)-3,5-di-methylpyrazole, instead of the hydrazone. The 1,4-oxathiins, N-(5,6-dihydro-2-methyl-1,4-oxathiin-3-ylcarbonyl)-N′-phenylurea and 5,6-dihydro-2-methyl-1,4-oxathiin-3-carboxylic acid hydrazide rearrange to give 5-(2-hydroxyethylthio)-6-methyl-1-phenyluracil and 4-(2-hydroxyethylthio)-3-methyl-2-pyrazolin-5-one, respectively. Finally, treatment of 5,6-dihydro-2-methyl-1,4-oxathiin-3-carbonyl chloride with 2-aminopyridine and with 2-aminopyrimidine affords 4H-3-(2-hydroxyethylthio)-2-methyl-pyrido[1,2-a]pyrimidin-4-one and 4H-3-(2-hydroxyethylthio)-2-methylpyrimido[1,2-a]pyrimidin-4-one, respectively, as the predominant products.