The present invention relates to a process for the synthesis of 3,4,6-trifluorophthalonitrile. This compound is a useful intermediate in the synthesis of 2,4,5-trifluorobenzoic acid which, in turn, is a starting material for quinolone antibiotics such as those disclosed in U.S. Pat. Nos. 4,571,396 and 4,861,779.
The synthesis of 2,4,5-trifluorobenzoic acid from 3,4,6-trifluorophthalic acid has been reported in Japanese Kokai Patent SHO 64-52737. Japanese Kokai Patent Hei 1-258639 discloses a process for preparing 2,4,5-trifluorobenzoic acid from 2,4,5,6-tetrafluoroisophthalonitrile wherein the first step comprises reductive defluorination to 2,4,5-trifluoroisophthalonitrile.
A method for the preparation of 3,4,6-trifluorophthalonitrile from 3,4,5,6-tetrafluorophthalonitrile, via reductive defluorination, has been reported in Japanese Kokai Patent Hei 1-160944. In this process, however, the yields are inconsistent and a significant amount of over-reduced material 3,6-difluorophthalonitrile, is produced.
3,4,6-Trichlorophthalonitrile is also known in the art and is disclosed as a starting material for the synthesis of iminoisoindolinone dyes in U.S. Pat. No. 3,887,581. One reported method of product 3,4,6-trichlorophthalonitrile is from 3,4,5,6-tetrachlorophthalonitrile via photolysis in the presence of 1,4-dimethoxybenzene (J.C.S. Chem. Comm., p. 566 (1980)). This process is not convenient for large scale production, however, because both the photochemical reaction and separation from the 1,4-dimethoxybenzene are difficult to perform.
The process of the present invention overcomes the aforementioned problems. For example, the present process is readily amenable to large scale production, as it utilizes readily-available reagents, is easily controlled and produces very little of the over-reduced material.