Study On Preparation Methods Of2,3-pyridinedicarboxylic Acid From Quinoline

2,3-pyridinedicarboxylic acid, a significant pesticide, pharmaceutical and dye intermediate, can be used to synthesis of p-fluoroethoxybenzene, moxifloxacin, nikethamide, imidazolinone herbicides and quinolone antibiotics. Nicotinic acid can be used to synthesize drugs for treatment of skin diseases, hypertension and coronary heart disease. It is also available as pharmaceutical intermediates for producing isoniazid, nikethamide and hexanicit.Nowadays, industrial preparation of2,3-pyridinedicarboxylic acid is mainly on oxidation of quinoline or quinoline derivatives. The oxidants include potassium permanganate, sodium hypochlorite, hydrogen peroxide, ozone, etc. However, the above-mentioned methods, to some extent, have some drawbacks such as high equipment prices, high energy consumption, low yield, difficulty in wastewater treatment, etc. High-purity nicotinic acid can be prepared from2,3-pyridinedicarboxylic acid via decarboxylation and sublimation at high temperature, but this method has high requirements for equipment.According to literatures, we tried several oxidants such as potassium permanganate, hydrogen peroxide, sodium hypochlorite, sodium chlorate, etc. Besides, ZnO/DMF oxidation and NHPI-catalyzed molecular oxygen oxidation methods were tried, latter method was used naphthalene or methylpyridine as substrate in literatures. However, experimental result did not show significant oxidation effects. By comparison, NaClO3/CuSO4/H2SO4oxidation system has advantages of high yield of2,3-pyridinedicarboxylic acid, easy-operating work-up, small amounts of wastes. Copper quinolinate generated from oxidation can be converted to2,3-pyridinedicarboxylic acid via alkalization, decolorization, acidification and purification.We fully investigated the factors which might affect the yield of2,3-pyridinedicarboxylic acid by selection orthogonal experiment to find significant factors. And then the best values of the significant factors were determined by optimization orthogonal experiment. SPSS statistics19.0software, a kind of professional mathematical statistics software, was applied to analyze the experiment data. The optimal reaction conditions for the oxidation were as follows:n(quinoline):n(sodium chlorate):n(cupric sulfate):n(concentrated sulfuric acid)=1:3.5:1:3, reaction time24h at102℃and the dropwise addition time of sodium chlorate was10h. At last, we did an experiment to verify optimal reaction conditions. Result reveals that the average yield of2,3-pyridinedicarboxylic acid was66.4%,96.6%purity,97.7%after purification. Total reaction time was reduced to12h when we used the filtrate, left from last oxidation, as solvent.2,3-Pyridinedicarboxylic acid was refluxed in anisole and nicotinic acid was prepared in a yield of65.3%,85.3%purity. Although low reaction temperature, the yield can be further improved.