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The behavior of the 3,4-dihydro-1,3-dimethyl-4-0xoquinazolinium ion (Q') in basic aqueous solution (pH 7-1 4 ) has been studied. Kinetic studies afforded information about four distinct processes: (a) the relatively fast equilibration of Q' with its pseudobase QOH; (b) the slower equilibration of the manifold comprised of Q' , QOH, the pseudobase anion QO-, and the ring-opened form, a formanilide derivative, F (equilibrium is approachable starting from Q' or from F, which exists in solution as a 3:1 mixture of two atropisomers); (c) slower equilibration of the less stable atropisomer of F into the same manifold as above; and (d) hydroxide ion catalyzed hydrolysis of the formanilide moiety to give the benzamide A. The species QOH and QO-, which are observable by UV and NMR spectroscopy, are tetrahedral intermediates at the carboxylic acid level of oxidation. The present work is a rare instance where such intermediates have been observed and where analysis of the kinetic data has provided rate constants for their formation and decomposition starting from different precursors. In strongly basic solutions the equilibrium F s QO-+ H+ is displaced toward QO-; that is, the tetrahedral intermediate anion is thermodynamically stable relative to its acyl precursor. (6) (a) Patchornik, A.; Berger, A,; Katchalski, E.

. Can. J. Chem. 63, 121 (I 985). Kinetic studies are reported for the base hydrolysis to phthalamic acid anions (H) and ammonolysis to phthalamides (A) for seven phthalimides (P): 1. unsubstituted; 2, 4-NOZ; 3, 4-CI; 4, 4-tBu; 5, 3-NO2; 6, 3-Me; 7, 3-Me3Si. The hydrolysis kinetics require two mechanisms, one which is first order in neutral imide and first ordcr in hydroxide ion, and a second, which is important only in quite concentrated NaOH, which is first ordcr in neutral phthalimide and second order in hydroxide ion. Ammonolysis kinetics for 1-5 revealed the rate law: Rate = k, [Unionized phthalimide] [NH3][OH-1. A mechanism is proposed with rate-determining breakdown of the anionic form of the tetrahedral intermcdiatc derived by addition of NH, to the phthalimide. The ammonolysis is reversible. The phthalamide hydrolyzes to the phthalamic acid via cyclization to an intermediate phthalimide, which is detected in concentrated base where its formation from phthalamide is more rapid than its subsequent hydrolysis. Rate constants for the cyclization follow the rate law: Rate = kc,, [Phthalamide:I[OH-1. This reaction is the microscopic reverse of the ammonolysis, and the ratio kN/k,,, provides the equilibrium constant Kc, for the reaction P + N H = A. Values for 1-5 lie in the range 2 X 10'-4 x lo'. With 3-methylphthalimide, kinetics in aqueous ammonia do not obey a first-order relationship. but they could be analyzed by a scheme whereby the phthalimide is converted reversibly to the phthalamide and simultaneously undergoes an irreversible hydrolysis. Thc value of K,, in the system is 1.8. With 3-trimethylsilylphthalimide the value of Kc, is further reduced to 0.01. The ammonolysis reaction does occur more quickly than hydrolysis but the equilibrium is so unfavorable that evcn in concentrated ammonia only a small amount of the phthalamide is ever formed. On propose un mtcanisme dont I'ttape dtterminante est la rupture de la forme anionique de I'intermtdiaire tttratdrique provenant de I'addition du NH3 sur la phtalimide. L'ammonolyse est rtversible. La phtalamide s'hydrolyse en acide phtalamique par le biais d'une cyclisation conduisant a une phtalimide intermtdiaire que I'on peut dtceler lorsque la reaction est rtalistc en presence de base concentrte; dans ces conditions la formation de cet intermtdiaire cst plus rapide quc son hydrolyse substquente. Les constantes de vitesse pour la cyclisation pcuvent Ctre reprCscnttes par I'tquation suivante: Vitesse = kc,, [PhtalamidcIl[OH-1. Sur une base microscopiquc, cette rtaction constituc I'inverse dc I'ammonolyse et le rapport kN/k,,, fournit la constante d'tquilibre Kc, de la rtaction P + NH3 = A. Les valeurs de Kc,, pour les composts 1 a 5 s'ttalent de 2 X 10' a 4 X 10.'. Dans le cas de la methyl-3 phtalimide en milieu ammoniacal aqueux, la cinttique n'obtit pas a la relation d'ordre un; on peut toutefois rationaliser ses donntes cinttiques en faisant appel un mdcanisme impliquant une transformation rtversible de la phtalimide en phtalamide accompagnte d'une hydroly...

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