Studies on pyrimidine derivatives. XVIII. Reaction of active methyl groups on pyrimidine N-oxides.

Abstract

Knoevenagel-type condensation and the Mannich reaction were investigated with various pyridine N-oxides having an active methyl group. For example, 6-methyl-4-phenylpyrimidine 1-oxide (Va) readily reacted with benzaldehyde in an aqueous ethanolic solution of potassium hydroxide, while 4-methyl-6-phenylpyrimidine (IVa) failed to react with benzaldehyde under the same conditions. When Va was treated with piperidine hydrochloride and paraformaldehyde, bis piperidinomethylation occurred at the 6-methyl group. The product was transformed into 4-phenyl-6-(2-piperidinoethyl) pyrimidine 1-oxide (XXIIa) by treatment with 5% sulfuric acid at 90°.