Characterization of 2-amino-3,4-dihydropyrimidine derivatives (& purification of biologically active substances from stichopus japonicus selenka)

Abstract

2-Amino-3,4-dihydropyrimidine derivatives containing guanidine moiety were effectively synthesized by the cyclization of free guanidine derivatives with α,β-unsaturated carbonyl compounds such as mesityl oxide, benzalacetophenone and dypnone in tertiary butanol at 25℃ in good yields. But the yields decreased at either high reaction temperature or polar protic solvents such as water, methanol or ethanol in contrast to the case of tertiary butanol. Their stabilities were determined in polar protic solvents without base and with base by the UV spectra. The structural change for the 2-amino-3,4-dihydropyrimidine derivatives were also observed by $^1H$ nmr spectra under the elevated temperature. Thus, it was concluded that 2-amino-3,4-dihydro-4,4,6,-trimethyl-pyrimidine was very unstable in water and methanol, but stable in tertiary butanol. While 2-amino-3,4-dihydro-4,6-diphenylpyrimidine was relatively stable and 2-amino-3,4-dihydro-4-methyl-4,6-diphenylpyrimidine was very stable in water or methanol. These compounds were stable in isopropanol, tertiary butanol and dimethyl sulfoxide at room temperature. However, 2-amino-3,4-dihydro-4,6-diphenylpyrimidine was converted to the corresponding pyrimidine in aqueous methanol in the presence of sodium hydroxide(pH＞10) under reflux. Tertiary butanol and dimethyl sulfoxide are found to be good solvents for the syntheses of the 2-amino-3,4-dihydropyrimidine derivatives at room temperature.