Equilibrium studies of 5-substituted 4-hydroxy-2-methylpyrimidines. V. Lactim-lactam tautomerism in ethereal solvents.

Abstract

Lactim-lactam tautomerism of 5-carbethoxy-4-hydroxy-2-methylpyrimidine (1) was examined in the ethereal solvents (ethyl ether, n-propyl ether, isopropyl ether, n-butyl ether and p-dioxane). Compound 1 existed as a mixture of the lactim form (4-pyrimidinol, I) and the lactam form (4(3H)-pyrimidone, IIb) in the ethers, except p-dioxane. In p-dioxane, 1 existed mainly in the lactam form, IIb. A method was deviced to estimate spectrophotometrically the tautomeric equilibrium constant (Kt ; Kt=[IIb]/[I]). The lactim form decreased with increasing the polarity of the solvent, 9.0% (IIb, 91.0%) in isopropyl ether ; 10.5% (IIb, 89.5%) in n-propyl ether and 14.7% (IIb, 85.3%) in n-butyl ether. The lactim-lactam tautomerism of 2-hydroxynicotinic acid esters (ester R ; CH3 (5), n-C8H17 (5')) and 4-hydroxynicotinic acid esters (ester R ; CH3 (8), n-C8H17 (8')) was also examined because of a structural resemblance to 1. Compound 5 existed as a mixture of the lactim form (2-pyridinol) and the lactam form (2(1H)-pyridone) in the ethers. The lactim form of 5 existed in amounts, 10-70% (lactam form ; 30-90%). Compound 8 existed mainly in the lactim form (4-pyridinol) in all the ethers. The presence of the lactim form may be resulted form an intramolecular hydrogen bonding of these compounds.