STUDIES IN HETEROCYCLIC CHEMISTRY .3. MECHANISM OF FORMATION OF BENZIMIDAZOLES FROM OMICRON-AMINO ANILIDES

The cyclization of o-aminoacetanilide provides a route to 2-methylbenzimidazole under a wide range of conditions. The kinetics of the reaction have been studied over the pH range -2-12·5; for comparison purposes the cyclizations of the two isomeric N-Me derivatives, o-aminobenzanilide, and o-aminotrifluoroacetanilide have been examined. The experimentally determined pseudo first-order rate constants show the influence of catalysis by acids and bases according to the expression: k = ko + kH+[H+]/(1 + kc[H+]) + kOH-[OH-] + kHA[HA] + kA[HA] + kA-[A-] The results indicate that under both acidic and basic conditions the slow step in the cyclization reaction is formation of hydroxybenzimidazoline. Base catalysis is ascribed to proton abstraction from the amino group being concerted with the nucleophilic attack. The greater efficiency of acid catalysis (kH+/kOH- = 5000) is attributed to the ability of the amino group to act both as a proton trap and subsequently as an intrammolecular general acid. Under strongly acidic conditions when both the amino and amido groups are protonated hydrolysis to o-phenylenediamine becomes important. © 1969.