Development of a continuous flow process for the synthesis of mesotrione

Mesotrione is an important 2-(substituted benzoyl)-1,3-cyclohexanediones herbicide. In the reported literatures, the main synthesis methods are rearrangement after esterification of 1,3-cyclohexanedione and 2-nitro-4-methylsulfonyl benzoyl chloride. However, in the esterification process, due to the presence of alkali, reaction heat of hydrogen chloride and alkali may lead to runaway reaction, and most of the catalysts for the rearrangement reaction are highly toxic, present processes have certain risks. According to recent reports, flow chemistry has many advantages especially good heat transfer efficiency and lower exposure to hazardous materials, can solve current problems in industrial production. Therefore, we optimized these two reactions in continuous flow by single factor study and kinetics. The yield of esterification product is 99% and purity is 98.6%. The yield of rearrangement product is 91.2% and purity is 99.3%. Finally, the process of full continuous esterification-rearrangement to synthesis mesotrione was successfully developed and harmless treatment of acetone cyanohydrin achieved in flow as well. The total yield is 90.5% with purity >99%. Graphical abstract