Oxidation of 4-halo-2-nitrotoluene with tetrabutylammonium permanganate in pyridine : Development and safety evaluation

4-Halo-2-nitrobenzoic acids are synthesized by oxidation of 4-halo-2-nitrotoluene with tetrabutylammonium permanganate (TBAP) in pyridine in multigram quantities. A significant induction period is observed at room temperature, and the vigorous exothermic reaction presents the risk of a run-away reaction. By control-feeding cold TBAP into the reaction mixture at 60 °C, the initiation process is managed, and the reaction is safely performed on multigram scale. However, larger-scale reaction is NOT recommended, and use of appropriate equipments is strongly encouraged.