Direct carboxylation of thiophene with CO2 in the solvent-free carboxylate-carbonate molten medium: Experimental and mechanistic insights

A feasible synthesis route is devised for realizing direct carboxylation of thiophene and CO2 in a relatively mild solvent-free carboxylate-assisted carbonate (semi) molten medium. The effects of reaction factors on product yield are investigated, and the phase behavior analysis of the reaction medium is detected through the thermal characterization techniques. Product yield varies with the alternative carboxylate co-salts, which is attributed to the difference in deprotonation capacity caused by the base effect within the system. Besides, the detailed mechanism of this carbonate-promoted carboxylation reaction is studied, including two consecutive steps of the formation of carbanion through breaking the CH bond(s) via the carbonate and the nucleophile attacking the weak electrophile CO2 to form CC bond(s). The activation energy barrier in CH activation step is higher than the following CO2 insertion step whether for the formation of the mono- and/or di-carboxylate, which is in good agreement with that of kinetic isotope effect (KIE) experiments, indicating that the CH deprotonation is slow and the forming presumed carbanion reacts rapidly with CO2. Both the activation energy barriers in deprotonation steps are the minimal for the cesium cluster system since there have the weak the cesium Cs-heteroatom S (thiophene) and Cs-the broken proton interactions compared to the K2CO3 system, which is likely to enhance the acidity of CH bond, lowering the CH activation barrier. Besides, these mechanistic insights are further assessed by investigating base and CH substrate effects via replacing Cs2CO3 with K2CO3 and furoate (1a) with thiophene monocarboxylate (1b) or benzoate (1c).