Concise Process for Pyriftalid Synthesis by Introducing the Mercapto Group Directly from a Nitro Group

A concise and efficient process for the synthesis of pyriftalid is described herein. The improved process features the direct introduction of the mercapto group by one-step substitution of a nitro group using sodium sulfide and elemental sulfur. A systematic study of the key step is also carried out in this article. Compared with previous routes, the optimized route is shorter and avoids a hazardous catalytic reduction and a subsequent diazotization reaction. Salt waste generated in workup is reduced as well. Pyriftalid is obtained in 68% overall yield and 99.88% purity in five steps with 3-nitrophthalic acid as the starting material.