A Sequential Condensation and Carbodiimide-Catalyzed Esterification Strategy for Efficient Synthesis of Benzothiazole–Imine–Cinnamate Hybrids

A sequential condensation–esterification strategy for efficient synthesis of benzothiazole–imine–cinnamate hybrids has been developed under ambient conditions. The synthetic route involves the initial Schiff base formation between ۲-aminobenzothiazole and ۴-hydroxybenzaldehyde, affording the corresponding imine intermediate in high yield (۸۸%), followed by carbodiimide-mediated esterification with trans-cinnamic acid Systematic optimization of the coupling step identified reaction time and catalyst loading as key parameters influencing conversion. A pronounced time-dependent increase in yield was observed, consistent with the formation and subsequent consumption of activated acyl intermediates under the mild reaction conditions employed. The addition of catalytic DMAP significantly enhanced reaction efficiency through the formation of a reactive acyl-pyridinium intermediate; however, excessive DMAP loading resulted in diminished yields, likely due to the stabilization of intermediates or competing N-acylurea formation. The optimal condition using DCC (۱ mmol) and DMAP (۰.۲۵ mmol) in DCM as a solvent at room temperature (۶ h) afforded the desired hybrid in ۸۶% yield, outperforming DCC alone (۶۲%) and higher DMAP concentrations (۶۷-۶۹%). In comparison, EDC·HCl-mediated coupling under identical conditions provided only moderate yields (up to ۵۴%), underscoring the importance of coupling reagent selection and mechanistic balance. Overall, this research demonstrates that controlled carbodiimide activation under ambient conditions enables efficient assembly of conjugated benzothiazole-based hybrids, providing a practical and mechanistically rational platform for constructing multifunctional heterocyclic frameworks.

کلیدواژه ها:

Benzothiazole-Schiff base ، Cinnamate ester ، Sequential synthesis ، Carbodiimide coupling ، Molecular hybridization