FACILITATED INTRAMOLECULAR CONJUGATE ADDITION OF AMIDES OF ETHYL-1',4'-CYCLOHEXADIENYL)-3,3-DIMETHYLPROPIONIC ACID .2. KINETICS OF DEGRADATION

The chemical stability studies of amides of '-dioxo-2',4'-dimethyl-1', 4'-cyclohexadienyl)-3,3- dimethylpropionic acid (Qa) [Qop(a-j)] were c onducted in order to determine the utility of this redox-sensitive sys tem as a potential prodrug promoiety or redox-sensitive protecting gro up in organic synthesis. This study showed that quinone propionic amid es of aniline derivatives [Qop-(a-d)] underwent rapid degradation in m ildly acidic conditions (pH 4.5-6.0) to yield degradation products res ulting from the intramolecular 1,2- or 1,4- conjugate addition of the amide nitrogen to the quinone ring. This conjugate addition was found to be specific base-catalyzed and independent of the para substituent on the aromatic ring of the amine. The predominant route of degradatio n yielded a five-membered ring spirolactam. By altering the nature of the amine component of the amide, these degradation reactions were pre vented, Amides of Qa other than those of the aniline type [Qop(e-j)] w ere found to be substantially more stable and were thus proposed as th e more suitable candidates for this potential redox-sensitive prodrug system and redox-sensitive protecting group for amines and alcohols in organic synthesis.