Pyrimidine derivatives. XI. Facile carbon-carbon bond-cleavage reaction of 6-bromomethylpyrimidinediones and (2,4-dioxo-1,2,3,4-tetrahydropyrimidin-6-yl)methyl nitrate via 6-formyl derivatives

Article abstract of DOI:10.1248/cpb.41.2073

The reaction of 5-bromo-6-bromomethyl-1,3-dimethyl- (1a) and 5-bromo-6-bromomethyl-1-(3-bromopropyl)-3-methyl-2,4(1H,3H)-pyrimidined ione (4a) with 1.0 and 2.0 eq of the sodium salt of 2-nitropropane yielded a mixture of 6-formyl (2 and 5a) and carbon-carbon bond-cleavage products (3 and 6a). When a large excess of the sodium salt of 2-nitropropane was used, 3 and 6a were obtained as sole products, respectively. The nitrates [(5-bromo-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-6-yl)methy l nitrate (1b) and the dinitrate of 5-bromo-6-hydroxymethyl-1-(3-hydroxypropyl)-3-methyl-2,4(1H,3H)-pyrimid inedione (4b)] were exclusively converted to 6-formylpyrimidines (2 and 5b) or 6-unsubstituted pyrimidinediones (3 and 6b) by reaction with 1.0 or 2.0 eq of sodium methoxide, respectively. The dinitrate of 5-bromo-1-(2-hydroxyethyl)-6-hydroxymethyl-3-methyl-2,4(1H,3H)-pyrimidi nediones (7) was treated with sodium methoxide to yield 2-(5-bromo-6-formyl-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl )ethyl nitrate (8), a 3,4-dihydropyrimido[6,1-c][1,4]oxazine derivative (9) and 2-(5-bromo-3-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)ethyl nitrate (10). A plausible reaction mechanism is presented.