2,3,4-tri:chloro-5-fluoro-benzoic acid or benzoyl chloride prodn. - by selective chlorination of corresp. 2,4-di:chloro cpd., intermediates for quinolone carboxylic acid antibacterials

摘要

Prodn. of 2,3,4-trichloro-5-fluorobenzoic acid (I) or its acyl chloride (Ia), comprises chlorinating 2,4-dichloro-5-fluorobenzoic acid (II), or its acyl chloride (IIa). To prepare (I), (II) is chlorinated in chlorosulphonic acid, using iodine as catalyst. To prepare (Ia), (IIa) is chlorinated without solvent, using Fe and/or FeCl3 as catalyst. Pref. (II) and (IIa) are known from DE3631906 and 3142856. (II) is reacted at 20-100 (pref. 50-60) deg.C and (IIa) at 50-150 (pref. 95-105) deg.C. Chlorine is 1-20 (pref. 1-2) moles per mol starting material. USE/ADVANTAGE - (I) and (Ia) are intermediates in synthesis of highly active quinolone carboxylic antibacterials (see e.g. EP126335), esp. via Cl/F exchange to 3-chloro-2,4,5-trifluorobenzoyl chloride. This method provides direct ring chlorination at 3 position with high selectivity, and (Ia) undergoes subsequent Cl/F exchange easily and with high selectivity.