Collect. Czech. Chem. Commun. 1998, 63, 394-406

Kinetics and Mechanism of Cyclization of Substituted 2-(Benzoylamino)alkanamides in Strongly Basic Medium

Miloš Sedlák, Jaromír Kaválek, Petr Mitaš and Vladimír Macháček

Department of Organic Chemistry, University of Pardubice, 532 10 Pardubice, Czech Republic


The cyclization reaction of substituted 2-(benzoylamino)alkanamides 1a-1i giving the corresponding substituted 2-phenylimidazol-4(5H)-ones 2a-2i has been studied. The equilibrium constants of reactions of compounds 1d-1f and 2-[(4-nitrobenzoyl)amino]-2,3-dimethylbutanenitrile (3) with methoxide have been determined in methanol-dimethyl sulfoxide media. For compound 1d and N-methyl derivatives 1a-1c, the cyclization rate constants have been measured in dependence on methoxide concentration in media of varying contents of dimethyl sulfoxide. The cyclization reaction mechanism involves formation of anion in a rapid pre-equilibrium and subsequent rate-limiting step: either formation of a cyclic intermediate or splitting off of OH- ion from this intermediate. The product formed in the given medium is immediately transformed into its conjugate base. A change in reaction medium affects the reactions of all the compounds in the same way. The ratio of concentration of substrate to that of its anion at low methoxide concentrations is affected by the solvent composition (MeOH-DMSO). At higher methoxide and DMSO concentrations the reaction rate distinctly decreases, which can be interpreted by the transformation of reactive anion into non-reactive dianion. The corresponding N-methylbenzoylamino compounds are cyclized faster by a factor of 400 as compared with compounds having no methyl group at the benzamide group.

Keywords: Reaction kinetics; Mechanism of cyclization; 2-Phenylimidazol-4(5H)-ones; Dissociation constants; Solvent effect.