An elementary study of the industrialized preparation of 1,1-difluoro acetone: Starting material of fluoropyrazole succinate dehydrogenase inhibitor

Abstract

In recent years, the development and increasing market presence of fungicides incorporating a fluoropyrazole ring, recognized as succinate dehydrogenase inhibitor fungicides, has gained momentum. The fluoropyrazole ring stands as the foundational nucleus of these fungicides, with its production cost being a pivotal concern for chemical industries. Significantly, the cost of 1,1-difluoro acetone largely influences this manufacturing cost. A cost-effective availability of 1,1-difluoro acetone could revolutionize the current methodologies for fluoropyrazole ring synthesis, primarily due to its enhanced safety and environmental sustainability. This study introduces an industrialized production methodology for 1,1-difluoro acetone, underlining its economic efficiency. Originating from ethyl acetoacetate, dibromide is synthesized in n-heptanol through the Oxone/KBr system. Following a fluorine-bromine exchange reaction with potassium fluoride, difluoride is obtained. Subsequent hydrolysis of the difluoride using 50% sulfuric acid leads to the formation of 1,1-difluoro acetone. Notably, while bromination and fluorination stages employ tubular reactors, hydrolysis, and decarboxylation are achieved in standard reactors. Optimal bromination conditions were identified as 2.2 equivalent bromination reagent, temperature>60℃, and atmospheric pressure. The fluorination conditions mirror those of bromination, with the fluorinating agent being 2.2 equivalent and a reaction temperature of 150℃. For hydrolysis and decarboxylation, 50% sulfuric acid concentration at 90℃ was optimal, yielding a crude product with a 99.60% G.C. content and a 91.25% efficiency. The outlined production process of 1,1-difluoro acetone boasts remarkable cost efficiency and procedural simplicity, positioning it favorably for industrial applications. This innovative approach promises significant manufacturing cost reductions, endowing fungicides with a fluoropyrazole ring a competitive edge in the market. Such advancements are anticipated to foster market expansion, ultimately benefiting agricultural practitioners.