4-Acylamino-4H-1,2,4-triazoles and related structures: new investigations of their chemical and physicochemical properties associated with their particular exocyclic amide function

Abstract

The acido-basic behavior of 4-acylamino-4H-1,2,4-triazoles and of the related structures, 4-acylamino-4H-1,2,4-triazolium salts, 4-acylamino-1,2,4-triazoline-3-thiones, and 4-acylamino-1,2,4-triazolin-3-ones, has been compared. Among the triazolium salts examined, the 1-carboxymethyl-4-phenylacetylamino derivative has been selected as a particular triazolium salt bearing two acidic centres, a carboxylic acid group and an exocyclic amide group. This compound has been isolated in three different ionic forms corresponding to different protonation and deprotonation states of the molecule. For these compounds, IR, NMR, and X-ray data were compared and the preferential localization site of the labile proton on the betainic intermediate structure has been discussed. Taking into account that deprotonation of the amide function of 4-acylamino-4H-1,2,4-triazolium salts may introduce a negative pole in the proximity of the strong electrophilic carbon atom in the 2-position of the ring, reactivity of different triazolium salts toward the nucleophilic addition of the hydride ion has been compared. In particular, 4-acylamino-4H-1,2,4-triazolium salts free of alkyl substituent on the amide nitrogen failed to give the corresponding 4-acylamino-Δ2-1,2,4-triazolines after reaction with the hydride ion, while, under the same conditions, the 4-N-methyl derivatives were transformed into this unusual ring system in good yields. In this case, no decrease of reactivity toward the nucleophilic agent was observed since, as a result of the N-al-kylation, no deprotonation of the amide group can occur in these alkaline experimental conditions.