MECHANISM OF ALKALINE CYCLIZATION OF 2-(SUBSTITUTED BENZAMIDO)BENZAMIDES TO 4-QUINAZOLINONES

The title amides cyclize rapidly to the corresponding quinazolin-4-one s in aqueous alkaline solution at 25 degrees C; the pseudo-first-order rate constants fit the empirical equation k(obs) = k(max) [OH-]/K-m [OH-] + [OH-]K-2(m')) where K-m' is essentially zero for all except t he 4-nitro species. The value of K-m measures the ionization of the ne utral amide 1 to nonproductive conjugate base 2. Studies of the cycliz ation in alkali of 2-benzamido-N-methylbenzamide (1i) and 2-(N-methylb enzamido)benzamide (1j) indicate that 7 carries over 99% of the reacti on flux and that the tautomer 8 does not contribute significantly. The ratio k(max)/K-m, is a composite rate constant first order in 1 and f irst order in [OH-]. The value of the Hammett rho for k(max)/K-m (0.67 ) is consistent with the above scheme where decomposition of 7 is rate limiting.