STUDIES RELATED TO THE SYNTHESIS OF CHLORAMPHENICOL.Ⅲ AUTO-OXIDATION OF p-NITROETHYLBENZENE A NOVEL METHOD FOR THE PREPARATION OF p-NITROACETOPHENONE

A method for the preparation of p-nitroacetophenone was developed on the principle of auto-oxidation of p-nitroethylbenzene. The product could be isolated in good quality by a process of simple freezing, Manganese acetate on calcium carbonate (1:10) was found to be the catalyst of choice. When a steady current of oxygen was bubbled through p-nitroethylbenzene at the rate of 0.55 ml. per minute for every gram of the mass, with stirring, at 140-145℃, and in the presence of catalyst equivalent to 0.005 to 0.01% by weight of Mn⁺⁺, p-nitroacetophenone content could be raised to a maximum of 62% within 18 to 30 hours. p-Nitrobenzoic acid and formic acid were also formed alongside with p-nitroacetophenone in an amount approximately 10% its weight, together with probably a trace of nitrophenols which was not identified. From 453 g. of p-nitroethylbenzene, after oxygenation and being chilled, the crude product separated and washed with a solution of sodium carbonate at 70-80℃ to remove p-nitrobenzoic acid, 153-161 g. of p-nitroacetophenone was obtained, m. p. 79-80℃. Unchanged p-nitroethylbenzene could be reclaimed from the mother liquor by fractionation. The role of calcium carbonate in the catalyst is, however, not only that of a neutral carrier. It was shown to exert an important moderating effect on the decomposition of the peroxide radical which was essential for the maintainance of auto-oxidation reaction chain. When manganese acetate alone was used as catalyst, the reaction was usually rapid at the onset but of short duration. "Besides, the reaction would then be very sensitive to the presence of even minute amounts of copper and iron salts which were both potent peroxide destroyers. The presence of calcium carbonate would bring to a check these deleterious effects, giving reaction liquor of light colour and high phenone content. An un-identified inhibitor was found to be formed and accumulated during the reaction.