Copper-Catalyzed Decarboxylation of 2,4,5-Trifluorobenzoic Acid in NH3-Enriched High-Temperature Liquid Water

Abstract

1,2,4-Trifluorobenzene, the decarboxylation product of 2,4,5-trifluorobenzoic acid, is an important raw material for synthesizing sitagliptin phosphate, the main medicinal treatment for diabetes. The traditional synthesis suffers from environmental concerns; therefore, in this work, a series of metal catalysts was employed to catalyze the decarboxylation of 2,4,5-trifluorbenzoic acid in NH3-enriched high-temperature liquid water (HTLW) to address these concerns. Copper catalysts exhibited excellent performance, and heterogeneous copper catalysts, such as Cu and Cu2O, led to a higher yield of 1,2,4-trifluorobenzene (89.1%) than homogeneous copper catalysts, such as CuCl2 and CuCl. The effects of catalyst loading and reactant loading on the decarboxylation of 2,4,5-trifluorbenzoic acid were also investigated. Increases in the catalyst and reactant loadings were favorable for the decarboxylation of 2,4,5-trifluorbenzoic acid; however, a high catalyst loading was not favorable. A reusability test with Cu2O re...