Study On Carbonate Mediated Direct Carboxylation Of Thiophene And CO₂

The carbon dioxide（CO₂）,as the most significant greenhouse gas,is also a plentiful,cheap,and easily accessible,non-toxic,and unique C1 resource.The research on realizing high-value utilization of CO₂ through chemical conversion has high scientific significance and application value.Direct C–H carboxylation to produce the carboxylic acid derivatives is the hotspot for research and the challenge in the CO₂usage and transformation.Direct C–H carboxylation reactions reported so far are mainly limited to the substrates containing relatively active acidic C–H bonds,while there are few reports on the functionalization of inert C–H bonds.Based on the high atomic utilization and step economy of this synthesis path,a feasible synthesis route is devised for realizing the direct carboxylation of thiophene and CO₂ in the mixed carbonate-carboxylate system under the solvent-free condition,which realizes the effective utilization of thiophene and CO₂ resources,and overcomes the problems of multiple reaction steps,waste disposal in the traditional synthesis pathways.First,the effects of reaction factors（reaction temperature,substrate amount,CO₂pressure,and the carboxylate and carbonate type,etc.）on the product yield and selectivity of the carboxylation process are studied in the batch reactor.The state and stability of the mixed salt are analyzed by the thermal analysis technologies,such as high temperature in-situ XRD,and it is confirmed that the reaction is carried out in the molten phase.As discovered that only the“synergistic”effect of carbonate and carboxylate can aid the reaction to proceed efficiently,and product yield varies with the type of carboxylate and carbonate,that is,there has alkali effect.Besides,the auxiliary base not only has the effect of lowering the melting point of carbonate,but also its alkaline strength has a certain impact on the substrate deprotonation process,that is,the reaction process has the indispensable characteristic of simultaneous alkaline and molten state.Then,based on the single-factor experimental results,the reaction conditions are optimized by the Box-Behnken response surface methodology,and the corresponding mathematical models between the product yield and the key independent variables are established.According to the results of variance analysis,residual analysis and outlier detection of the regression models,the rationality and reliability of the models are confirmed.Based on the optimal reaction conditions given by the models,the corresponding validation experiments are carried out,and it is found that the experimental results are highly consistent with the predicted values.It is found that the quadratic effect of reaction temperature has the greatest impact on the product yield,and its contribution percentages are 33.63%and 30.18%,respectively.（1）When the thiophene amount is fixed,the optimum reaction conditions are the reaction temperature of 289℃,the proportion of cesium carbonate in the mixed salt of 28%,CO₂ pressure of 9.3 bar and the amount of mixed salt of 2.24 mmol.At this time,the product yield is 13.03%（average）and the selectivity of product monocarboxylic acid is 55.42%.（2）When the thiophene amount is used as the optimization variable,the optimum reaction conditions are the reaction temperature of 287℃,the proportion of cesium carbonate in the mixed salt of 32.20%,CO₂ pressure of 10 bar and the substrate thiophene amount of 9.35 mmol.And the product yield is 48.65%（average）and the selectivity of the dicarboxylic acid is 70.26%.Finally,the reaction mechanism of the carbonate-carboxylate system mediated carboxylation of thiophene and CO₂ is studied by using the density functional theory（DFT）,and the correctness of the simulation results is verified by the kinetic isotope effect（KIE）experiments.Results show that the deprotonation step induced by the base carbonate is the rate-determining step.The counter-cation simultaneously activates both the CO₂ and the nucleophile carbanion when the nucleophile carbanion attacks the weak electrophile CO₂,forming a transition state structure in which the counter-cation,the carbanion,and the carbon atom in the center of CO₂ are arranged in a ternary ring conformation.In order to further verify the rationality and reliability of the DFT results,the substitution effects of cesium-potassium element in mixed salts and aromatic substrates are investigated from the perspective of experiments and DFT calculations.Results indicate that there are differences in the reaction effects of the carboxylation reactions mediated by the different carboxylate-carbonate systems,and the trend predicted by the theoretical calculations is highly consistent with the experimental results.The distortion/interaction-activation strain model and the graphical method of interaction region indicator are used to reveal the roots for the differences in reactivity,that is,the different interaction between the counter-cation and heteroatom and broken proton on thiophene ring makes the acidity of C–H bond on thiophene ring different,resulting in the difference of reaction energy barrier（s）.Furthermore,based on the theoretical calculation results,that is,the difference in the deprotonation ability of potassium carbonate and cesium carbonate,the carboxylation reaction experiment mediated by the mixed Cs₂CO₃-K₂CO₃-Cs OPiv carbonate system is designed,which inhibits the degree of deep carboxylation transformation of substrate in a single carbonate system and improves the selectivity of the product monocarboxylate from 22.40%to 65.20%and the product yield（15.76%）is almost the same as that（18.52%）of the cesium acetate system in the single carbonate system.