Synthesis of pyrimidine derivatives

Abstract

Substituted guanidines reacted with α,β-unsaturated carbonyl compounds at room temperature in t-butanol to afford pure products of 2-aminodihydropyrimidines which are unstable in protic solvents such as water, methanol, and ethanol but quite stable in t-butanol. The instabilities of 2-aminodihydropyrimidines were studied by uv and $^1H$ nmr spectroscopy. The structures of 3,4-dihydropyrimidines synthesized from alkylguanidines with mesityl oxide were assigned as 2-alkylamino-4,4,6-trimethyl-3,4-dihydropyrimidines by comparing $^1H$ nmr, ir, and uv spectral data with those from 2-alkylamino-4,4,6-trimethyl-3,4-dihydropyrimidines synthesized from 4,4,6-trimethyl-1,2,3,4-tetrahydropyrimidin-2-thione by S-methylation and substitution by alkylamines. The structures of 5,6-dihydropyrimidin-4-ones synthesized from N-methyl- or N,N``-dimethylguanidine with methyl acrylate were assigned as 2-amino-1-methyl-or 1-methyl-2-methylamino-5,6-dihydropyrimidin-4-one by comparing $^1H$ nmr, ir, and uv spectral data with those from 2-amino-1-methyl- and 1-methyl-2-methylamino-5,6-dihydropyrimidin-4-one synthesized from 1-methyl-2-thio-5,6-dihydrouracil by S-methylation and substitution by ammonia water or methylamine. From these data, in case of the reaction of methylguanidine with methyl acrylate, the more basic methylamino group by electron donating methyl group first attacks β-carbon in methyl acrylate, which shows that the basicity is more important than the steric hindrance. The $λ_max$ values of the dihydropyrimidines showed significant differences from those of the hydrochlorides whose large blue shifts are good evidences and tools for the conjugative system of the two double bonds in 2-aminodihydropyrimidines. It is for the first time to isolate the pure 2-aminodihydropyrimidines and to elucidate their structures.