STERIC EFFECTS IN THE REACTIONS OF OXO-PYRIMIDINE DERIVATIVES .1. STERIC ACCELERATION OF HYDROLYSIS OF 5-MONOALKYL SUBSTITUTED BARBITURIC-ACID DERIVATIVES AS THE EFFECT OF 1'-BRANCHING

A series of 5-alkyl (or H) (R(1))-1-methyl (or H) (R(2)) substituted d erivatives (R(1) = N, Me, Et, iso-Pr and tert-Bu, 1-5) of barbituric a cid was investigated. Pseudo-first order kinetics of hydrolysis of the compounds in alkaline media have been estimated. One parameter free e nergy relationships (LFER) with Taft steric substituent constants (E(s )) are linear with the negative slope of -0.45 (R(2) = H) or ca. -1.5 (R(2) = Me). Assuming a thermodynamically controlled kinetics this eff ect can be interpreted in terms of a steric strain which destabilizes the substrate. The reversibility of the reaction and the steric inhibi tion of the reversed cyclization of product supports the accelerating effect of N-methyl substitution. The LFER were also found with free en thalpies of the tetrahedral intermediate (positive slope) and the fina l product - malonuric acid formation (negative slope) estimated by the semiempirical molecular orbital calculations (AM1). The parent compou nds (R1 = H) do not fulfill any correlations. The estimated rate const ants for 1a from the obtained regression equations are equal and lower than the experimental data by a factor of ca. 5.