Study On The Synthesis Of 2-Pyridinecarboxylic Acid By Direct And Indirect Electro-oxidation Of 2-Methylpyridine

2-pyridinecarboxylic acid (2-picolinic acid) is a very important intermediate in organic synthesis. It was used to synthesize mepivacaine in medicine industry. Its derivatives are the intermediate of herbicide and neuropathic medicine. Chromium picolinate is a new medicine for diabetes. But now it was synthesized by chemical-oxidation and air catalytic-oxidation methods. The chemical-oxidation method was used to synthesizing 2-pyridinecarboxylic acid by oxidation of 2-methylpyridine with KMnO₄ and SeO₂ as oxidants. Because of its low yield and high pollution, it was fallen into disuse in industry. The 2-methylpyridine was oxidized by oxygen in air with catalyst, Because of its low yield of raw material, the high cost and the short life of the catalyst, the air catalytic-oxidation methods has not been used. The electro-oxidation of 2-methylpyridine is a green synthesizing method friendly with the environments, which just using electricity and without using oxidant and no pollution to environment. Although the preparation method on nicotinic acid and isonicotinic acid by electro-oxidation of 3-methylpyridine (3-picoline) and 4-methylpyridine (4-picoline) was reported, no literature have been studied on the electro-oxidation of 2-methylpyridine and the oxidation of 2-methylpyridine with K₂Cr₂O₇ as oxidant before.Through the investigation on direct and indirect electro-oxidation (in-cell and ex-cell) with 2-methylpyridine as the initial material, We studied the oxidation of 2-methylpyridine detailedly. Five research sections were included. First, a new HPLC method was established to determine pyridine, 2-pyridinecarboxaldehyde, 2-methylpyridine and 2-pyridinecarboxylic acid. Second, 2-methylpyridine was oxidized to 2-pyridinecarboxylic acid using the direct electro-oxidation method. Third, using the in-cell indirect electro-oxidation method, 2-methylpyridine was oxidized to 2-pyridinecarboxylic acid in an electrolytic cell with K2Cr2O7 as an oxidant which was prepared by electrochemical oxidation of Cr3+. Fourth, 2-pyridinecarboxylic acid was prepared by the oxidation of 2-methylpyridine with potassium dichromate as an oxidant. Fifth, the electrochemical oxidation of Cr3+ was discussed. Both the fourth and the fifth sections were referred as ex-cell indirect electrochemical oxidation.In the first section, the analyzing method by reversed phase high performance liquid chromatography, the effect of different mobile phases, pH, methanol ratio, flow velocity and column temperature were studied.In the second section, the direct electro-oxidation of 2-methylpyridine took place in an electrolytic cell with or without proton exchange membrane respectively. The effect of temperature, the concentration of 2-methylpyridine and sulfate acid on anode reaction were studied by determination of the polarization curves. The effect of temperature, the concentration of 2-methylpyridine and sulfate acid, anode potential on current efficiency and selectivity were studied with or without civil proton exchange membrane. The best reacting conditions were found by the orthogonalizedexperiment and the analysis with HPLC. Under the optimum conditions in an electrolytic cell with proton exchange membrane, the highest selectivity was 95.3% and the current efficiency was 45.3%. Under the optimum conditions in an electrolytic cell without proton exchange membrane, the highest selectivity was 83.1% and the current efficiency was 34.9%.The reactions were expressed in following equations:The reaction of oxygen evolution was a competitive reaction that also took placed at anode:The main reaction took placed at cathode in the electrolytic cell with proton exchange membrane was hydrogen evolution:Besides hydrogen evolution, the reduction of 2-pyridinecarboxylic acid also took placed at cathode in the electrolytic cell without proton exchange membrane, thus the current efficiency and selectivity dropped.In the third section, the indirect electro-oxidation of 2-methylpyridine took place in an electrolytic cell with or without proton exchange membrane respectively. Cr³⁺ was oxidized to Cr2O^2-₇ in an electrolytic cell with or without proton exchange membrane, then Cr₂O^2-₇ which as an oxidant oxidize 2-methylpyridine to 2-pyridinecarboxylic acid. The effect of temperature, the concentration of 2-methylpyridine, sulfuric acid and chromium sulphate, as well as anode potential on current efficiency and selectivity were studied. The results indicated that the current efficiency andselectivity increased with the increasing of temperature, the concentration of sulfuric acid and chromium sulphate, and decreased with the increase of anode potential. Under the optimum conditions in an electrolytic cell without proton exchange membrane, the highest selectivity was 76.7% and the current efficiency was 19.2%. Under the optimum conditions in an electrolytic cell with proton exchange membrane, the highest selectivity was 80.9% and the current efficiency was 26.6%.It was found from the experiments that the main reaction which took place at the anode was the electro-oxidation of Cr³⁺ to Cr₂O^O2-₇. The chemical reaction which took place in the anodic cell was the oxidation of 2-methylpyridine by Cr₂O^2-₇. The reactions were expressed in following equations:In the fourth section, 2-pyridinecarboxylic acid was prepared by potassium dichromate oxidation method, the effect of temperature, sulfuric acid concentration, reaction time, the proportion and concentration of reactants on yield, conversion and selectivity were studied. The obtained product was separated and characterized. The results indicated that the yield and the selectivity of 2-pyridinecarboxylic acid were very high. Compared with other chemical methods, the reaction time was short and the reaction conditions were mild, the highest chromatographic yield was 89.1%, the selectivity was 89.2%In the fifth section, the anode oxidation and the electrochemicalbehaviors of Cr3+ with the civil proton exchange membrane were studied at PbO2, Pt, graphite electrode. Electro-oxidation conditions of Cr3+ were explored by the measurements of cyclic voltammetry and current efficiency at different electrodes. It was found that catalytic action of various electrode materials on Cr3+ oxidation was different. The PbO2 electrode shows good electrochemical stability and catalytic capability, and is superior to graphite and Pt electrode. After adding Ag+, the currnet efficiency increase obviously higher on PbO2 and Pt electrode than graphite electrode. Different metal ions have different supporting catalysis on the PbO2, the current efficiency increased little after adding Mn2+, but current efficiency decreased higher after adding Co2+. The effects of temperature, the concentration of sulfuric acid and chromium sulphate, reaction time and current density on current efficiency were studied in this section.Cr was oxidized to Cr2O72- in electrolytic cell which could be used repeatedly. The oxidation of 2-methylpyridine by Cr2O72- and the electro-oxidation of Cr3+ took place in respective equipments when using ex-cell indirect electro-oxidation. The advantages of ex-cell method are that both optimum conditions can be matched respectively when the chemical reaction and the electrochemical reaction require different conditions, but it has some problems such as it increases equipments and separate steps. The advantage of in-cell method was that fewer equipments can be used and the operation was easy because we needn't separate the organic phase and the water phase, but the conditions of the chemical reaction and the electrochemical reaction such as temperature, pH, composition of solution etc...