Synthesis of Enaminones-Based Benzo[d]imidazole Scaffold: Characterization and Molecular Insight Structure

Saeed Alshahrani,Matti Haukka,Abdullah Mohammed Al-Majid,Sammer Yousuf,Saied M Soliman,Abdullah Saleh Alamary,Assem Barakat

doi:10.3390/cryst10100955

Abstract

(E)-1-(1H-Benzo[d]imidazol-2-yl)-3-(dimethylamino)prop-2-en-1-one 2 was synthesized by one-pot synthesis protocol of 2-acetyl benzo[d]imidazole with dimethylformamide dimethylacetal (DMF-DMA) in xylene at 140 °C for 8 h. Reaction of enaminone derivative 1 with acetylacetone in the presence of AcOH/NH4OAc under reflux afforded the cyclized pyridino-benzo[d]imidazole derivative 3. The latter compound was converted into the corresponding β-enaminone 4 with DMF-DMA. The single crystal X-ray diffraction technique eventually confirmed the assigned chemical structure of the N-alkyl-β-enaminone 2 and pyridino-benzo[d]imidazole derivative 3. N-alkyl-β-enaminone 2 crystallized in the monoclinic space group P21/n with unit cell parameters of a = 9.8953(3) Å, b = 5.7545(2) Å, c = 21.7891(7) Å, and β =100.627(2)°, and with one molecule per asymmetric unit. On the other hand, compound 3 crystallized in the orthorhombic crystal system and space group P212121 with unit cell parameters of a = 6.82950(10) Å, b = 8.00540(10) Å, c = 22.4779(2) Å, and also with one molecule per asymmetric unit. Based on Hirshfeld analysis, the H...H (51.3%), O...H (10.0%), N...H (10.3%), and C...H (27.6%) contacts in 2 and the H...H (46.8%), O...H (9.9%), N...H (13.0%), and C...H (21.6%) in addition to the C…C (6.7%) interactions in 3 are the most important towards crystal stability via molecular packing. The main difference is the presence of π–π interaction among the molecular units of 3 but not in 2. The calculated 1H and 13C NMR chemical shifts showed good agreements with experimental data. Electronic properties and reactivity parameters of both compounds are also calculated and compared.

Highlights

Fused heterocycles based on benzimidazoles scaffold have been found in many biologically active natural products and pharmaceutical drugs [1]
In biological sciences, it has been approved to have a high pharmacological importance [23,24]. In this text and the continuation of our research program towards the synthesis of new heterocyclic hybrids [25,26,27,28,29,30], we explored the synthesis of two β-enaminones based on benzo[d]imidazole scaffolds by mixing 2-acetyl benzo[d]imidazole with dimethylformamide dimethylacetal (DMF-DMA) in xylene under thermal conditions
The synthesis of N-alkyl-βenaminone-based benzo[d]imidazole scaffold 2 was achieved by a reaction of 2-acetyl benzo[d]imidazole with DMF-DMA as outlined in Scheme 1

Summary

Introduction

Fused heterocycles based on benzimidazoles scaffold have been found in many biologically active natural products and pharmaceutical drugs [1]. Polydentate enaminone reagents have gained more attention in the last decade due to their utilization as synthons in organic synthesis transformation [14,15,16] These building blocks have dual electronic attitude and can be employed as electrophilic enones or act as nucleophilic enones in many chemical transformations for the construction of many cyclic compounds with interesting biological activities as antibacterial, antitumor, anti-convulsant, and anti-glycating agents, as well as enzyme inhibitors [17,18,19,20,21,22].

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Results

Conclusion