β-Ureido acids and dihydrouracils. Part 15. Effect of allylic strain on ring opening of 1,6-disubstituted dihydrouracils

Abstract

The rate profiles for the alkaline hydrolysis of some dihydrouracil and dihydro-orotic acid derivatives have been measured in order to assess the effect of allylic strain on the ring opening of 1,6-disubstituted dihydrouracils. The introduction of a 1-nitrogen-substituent in the 6-substituted compounds brings about a substantial decrease (40–500 times) in the observed rate constant which is second order in hydroxide ion (k₁k₃/k_–1). The rate decreases of the addition step, k₁, are moderate and in the range expected from the observed shifts in conformational equilibria towards the axial conformation which gives rise to a hindered transition state. The major contributions to the rate decreases arise from the ring-opening step, k₃/k_–1, and have been attributed to strains of the type associated with the gem-dimethyl effect upon ring closure.