Aerobic Oxidation of Methylpyridines to Pyridinecarboxylic Acids Catalyzed by N-Hydroxyphthalimide

Selective aerobic oxidation of methylpyridines to pyridinecarboxylic acids was successfully achieved by the use of a radical catalyst, N -hydroxyphthalimide (NHPI), in the presence of Co(II) and/or Mn(II) salts. The oxidation of 3-methylpyridine by NHPI combined with Co(OAc) 2 under O 2 (1 atm) in AcOH at 100 °C gave 3-pyridinecarboxylic acid (76%). The reaction was found to be enhanced by addition of a small amount of Mn(OAc) 2 to the catalytic system. The reaction with 20 atm of air, catalyzed by NHPI−Co(OAc) 2 −Mn(OAc) 2 at 150 °C for 1 h, gave 3-pyridinecarboxylic acid (85%). 4-Methylpyridine was much less easily oxidized than 3-methylpyridine. The co-oxidation of 3-methylpyridine and 4-methylpyridine by NHPI−Co(OAc) 2 −Mn(OAc) 2 at 150 °C for 5 h gave results that were better than those obtained from individual oxidations, forming 3-pyridinecarboxylic acid (93%) and 4-pyridinecarboxylic acid (70%). The NHPI-catalyzed oxidation of methylpyridines would provide an attractive direct method which has long been desired in the chemical industry for the manufacturing of pyridinecarboxylic acids.