Facile one-pot synthesis of novel N-benzimidazolyl-α-arylnitrones catalyzed by salts of transition metals

Abstract

A novel series of N-benzimidazol-2-yl-α-aryl nitrones 3a-j is synthesized via simple one-pot condensation/oxidation of 2-aminobenzimidazole, an aromatic aldehyde and m-chloro perbenzoic acid (m-CPBA) as an effective oxidant using Mn(NO₃)₂·6H₂O as an efficient catalyst at room temperature. All synthesized N-benzimidazolyl nitrones were identified using FTIR, NMR and mass spectroscopy. Also, stability energy theory calculations were performed and ¹H NMR computational spectra were generated for the isomeric structures of 3a; the results show that the stability order is oxaziridine (4) followed by the nitrones 3a _E and 3a _Z . Also, comparing the computational spectroscopy results with the experimental data shows great accordance with nitrone 3a _E . Among the remarkable points of this protocol, stable N-heterocyclic nitrones were prepared for the first time from raw materials under mild oxidative conditions. Therefore, they can easily be applied as high-potential intermediates for synthesizing valuable heterocycles in mild conditions. Due to benefits such as the use of inexpensive and available catalysts, short reaction times, high yields, facile workup to obtain pure product, and facile separation of the side product (m-chlorobenzoic acid), this simple protocol complies greatly with the principles of green chemistry.

Fig. 1. Natural structures with nitrone frameworks.

Fig. 2. Four main pathways of synthesis of nitrones and some of their synthetic applications.

Scheme 1. The model reaction for optimizing the reaction conditions.

Scheme 2. The synthetic pathway for the preparation of nitrones 3a–j.

Scheme 3. Proposed mechanism for the synthesis of compounds 3a–j.

Scheme 4. Synthesis of compounds 3a–j in two steps without catalyst and intermolecular hydrogen bonding (III).

Fig. 3. The optimized structures and relative energy comparison of the nitrone (3a_Z, _E) and oxaziridine (4) molecules.