Pyrimidine composition stability

Increasing the electron-donor properties of the R, substituent in the case of dihydro derivatives of 1,2,4-triazolo[l, 5-a]pyrimidines [X, Z are N, Y is C(R)], tetrazolo[l, 5-a]pyrimidines (X, Y, Z are N), and pyrimidofl, 2-a]benzimidazoles (X, Y are o-C() I4, Z is N) tends to stabilize the B form. This can be explained by the conjugation of Rj with the electron-withdrawing azomethine group and the azole moiety. Reduction of the electron-accepting properties of the azole fragment (imidazopyrimidines and pyrazolopyrimidines) decreases the influence of the Ri substituent on tautomeric composition. 

The pAj value for anhydrous quinazoline obtained using a rapid reaction apparatus is 1.95 at 20°C, as compared to the equilibrium pAf, value of 3.51 and to the pA, value of 7.77 for the hydrated species. The equilibrium pK value obtained by potentiometric titration or by spectrophotometry is a composite value arising from equilibrium between a stable hydrated cation and a stable anhydrous neutral species. Quinazoline in aqueous solution is a much stronger base (pAT = 3.51) than pyrimidine (pAT = 1.31) because its cation is stabilized as a covalent 3,4-hydrate. Most quinazoline derivatives in which the cation is capable of hydration are stronger bases than the corresponding pyrimidines. Substituents at the 4-position interfere with the covalent addition of water making the pK. values of 4-substituted quinazolines comparable with the pAf, values of the corresponding 4-substitiited pyrimidines (e.g., 4-methylquinazoline has pK 2.52, as compared to pK of 2.0 for 4-methylpyrimidine). The pAT values of several substituted quinazolines have been compiled. ... 

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