Facile synthesis of benzimidazoles via oxidative cyclization of aliphatic aldehyde with o-phenylenediamines, by DIPEA: An antimicrobial and in vivo evaluation of zebrafish embryos.

Cymbopogon citratus (lemongrass), a bioactive component of citral (1a), could be isolated and synthesised in semi-synthetic analogues with improved therapeutic properties. The first report describes citral (1a) as a starting material for the synthesis of benzimidazole derivatives citral (1a) between various o-phenylenediamines (2a-l) in the presence of DIPEA as a commercially available environmentally benign base and ethanol as a green solvent. The yield of all benzimidazole derivatives (3a-l) was between 68-76%; and characterised by 1H, 13C NMR, FTIR, and HR-MS (ESI) spectral data analysis. The semi-synthetically prepared benzimidazole derivatives (3a-l) were evaluated for their anti-bacterial and anti-fungal activity. The benzimidazole compounds (3a-b, and 3g-j) exhibit anti-microbial activity. In vivo toxicological tests on zebrafish embryos found that all of the benzimidazole compounds (3a-l) were non-toxic and had low embryotoxicity after 96 h, with an LC50 of 36.425 μM, which could facilitate the design of novel antimicrobial agents using a cost-effective method.