Benzethonium chloride:glycerol (1:2) deep eutectic solvent promoted green synthesis of benzo[4,5]imidazo[1,2- a ]pyrimidine-3-carboxylate and evaluation of its anti-diabetic activity

In this study, we present the preparation of benzethonium chloride:glycerol (1:2) deep eutectic solvent (DES) by mixing benzethonium chloride and glycerol in a 1:2 ratio and heating at 80 °C for approximately 30 min. The prepared BztCl:Gly DES was utilized as an eco-friendly reaction medium and an eco-benign catalyst for the one-pot multicomponent synthesis of ethyl 2-methyl-4-aryl-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylate derivatives via the cyclocondensation of equimolar amounts (5 mmol each) of aromatic aldehydes, ethyl acetoacetate, and 2-aminobenzimidazole at 110 °C. The reaction proceeded rapidly, affording 11 distinct benzo[4,5]imidazo[1,2-a]pyrimidine derivatives in excellent yields ranging from 77% to 93% within 45–90 min. The products were isolated by filtration, purified via recrystallization, and structurally confirmed using infrared spectroscopy (IR), proton and carbon nuclear magnetic resonance spectroscopy (1H and 1³C NMR), and electrospray ionization mass spectrometry (ESI-MS). BztCl:Gly DES was recovered by water addition, which precipitated the organic products. The aqueous phase was then evaporated under reduced pressure, enabling efficient reclamation and reuse BztCl:Gly DES. Remarkably, BztCl:Gly DES demonstrated excellent stability and sustained catalytic activity, maintaining its efficiency across five consecutive reaction cycles. The α-amylase inhibitory activity of the synthesized samples was evaluated across a concentration range of 25 to 500 μg/mL. All samples exhibited a clear dose-dependent inhibitory effect of IC50 value ranging 25–44 μg/mL, where the percentage of inhibition increased progressively with rising concentrations. Thus, BztCl:Gly DES acts as an efficient catalyst and reaction medium for this organic transformation by enables hydrogen bonding and nucleophilic activation, promoting imine formation and cyclization, collectively accelerating the reaction and improving product yield. This study presents the first use of a biocompatible, recyclable benzethonium chloride-based deep eutectic solvent (DES) as both a highly efficient catalyst and reaction medium for the synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine derivatives. Compared to traditional volatile organic solvent methods, this approach achieves excellent yields under mild conditions while offering promising in vitro α-glucosidase inhibitory activity.