Ammoxidation of 2-methylpyrazine to 2-cyanopyrazine was investigated on antimony, zirconia, cobalt, copper and manganese promoted vanadium phosphorus oxide (VPO) catalysts and antimony promoted alumina supported vanadium phosphorus oxide (Sb-VPO/Al2O3) catalyst under atmospheric pressure and at 400 0C. The catalysts were characterized by means of X-ray diffraction, electron spin resonance, infrared spectroscopy, scanning electron microscopy, ammonia chemisorption and BET surface area methods. The catalytic activity is correlated well with the physicochemical characteristics of the catalyst. Higher activity is observed for Sb-VPO-1 catalyst having lower surface area, lower oxidation state of vanadium and higher surface acidity. Sb-VPO/Al2O3 is active and selective in conversion of 2-methylpyrazine to 2-cyanopyrazine due to presence of VPO in highly dispersed state over Al2O3. Promoter antimony reduces V5+ to V4+ prevents the formation of deleterious phases and weakens V=O bond strength allowing rapid exchange of oxygen increasing selectivity towards 2-cyanopyrazine. Higher air to ammonia mole ratio enhances the activity and selectivity towards 2-cyanopyrazine. VPO catalyst showed better conversion and product selectivity than the zirconia, cobalt, copper and manganese promoted vanadium phosphorus oxide catalysts. Redox cycle between V4+ and V5+ and higher surface acidity favors formation of 2-cyanopyrazine.