Diversity‐oriented One‐pot Synthesis of Novel Imidazo[4′,5′:4,5]benzo[e][1,4]thiazepinones and Benzo[d]imidazolyl Thiazolidinones throughpTSA Promoted Cyclization and Evaluation of Antimicrobial and Anti‐inflammatory Activities

Abstract

In contrast to target‐oriented synthesis that aims to access precise regions of chemistry, diversity‐oriented synthesis via multicomponent synthesis populates chemical space broadly with small molecules having diverse structures. This study has achieved the diversity‐oriented synthesis of novel imidazo[4′,5′:4,5]benzo[e][1,4]thiazepinones (4) and benzo[d]imidazolyl thiazolidinones (5) controlled by the nature of substitution effect of the reaction component. The one‐pot reaction of benzimidazole 1, aromatic aldehyde 2, and mercaptoacetic acid 3 leads to the formation of imidazo[4′,5′:4,5]benzo[e][1,4]thiazepinones (4) with electron‐donating groups as substitution on aromatic aldehyde while electron‐withdrawing substitutions produced benzo[d]imidazolyl thiazolidinones (5). The title compounds (4) and (5) were evaluated for their antimicrobial and anti‐inflammatory activities.

Synthesis and antibacterial activity of a series of 2‐trifluoromethylbenzimidazole‐thiazolidinone derivatives

“…Similar benzimidazoles with a phenyl group at C‐2, instead of a trifluoromethyl group, also showed good antimicrobial activity, comparable with that of ciprofloxacin and 2,3‐disubstituted thiazolidinone‐benzimidazole hybrids with a methylthio group instead of the trifluromethyl group at C‐2 and a thiazolidinone group attached to a thiosemicarbazone at N‐1, showed a broad‐spectrum antibacterial activity, similar to ampicillin . 2‐Mercaptobenzimidazole‐4‐phenylthiazolidinone derivatives, with a thiol group at C‐2 instead of a trifluoromethyl group showed up to four‐fold better activity against strain‐specific bacteria than that of ciprofloxacin . Our results have shown better activity to those previously reported, with a broader spectrum, and have further shown the potential of the trifluoromethyl group to be a useful moiety to tag onto C‐2 of benzimidazoles to produce small molecules with good antibacterial activity.…”

“…Although forming thiazolidines with primary amines, aldehydes, and thioglycolic acid is common, conventional methods use harsh solvents such as DMF, dioxane, and toluene with long reaction times (16 h), whereas microwave methods use toluene as the solvent with shorter reaction times (5–10 min) . We have successfully synthesized the thiazolidinones from benzimidazole precursors using the eco‐friendly ethanol as solvent under microwave irradiation.…”

Synthesis of Novel Thiazolidin‐4‐ones and Thiazinan‐4‐ones Analogous to Rosiglitazone

“…The main synthetic route reported in literature involves three components: an aldehyde, a primary amine, and mercaptoacetic acid. New derivatives of 4‐thiazolidinones have been obtained by modifications of the 2‐position, 3‐position, and 5‐position .…”