Study On Synthesis Of 2,3-dimethoxy-5-methyl-1,4-benzoquinone

2,3-Dimethoxy-5-methyl-1,4-benzoquinone called coenzyme Q0,a key fragment in coenzyme Qn series and a key intermediate for synthesizing coenzyme Q10 ,it can also be used to slow down the nervous system disorder and be used as hair dye. Based on the literature search, a commercial and practical synthesis route with p-cresol as a raw material was chosen. Coenzyme Q0 was prepared by oxidation bromination of p-cresol, methoxylation of 2,6-dibromide-p-cresol,following methylation of 2,6- dimethoxy-p-cresol, involving Vilsmeier-Haack Reaction, gave 3,4,5- trimethoxybenzaldehyde. the next step, involving Dakin Reaction with p- toluensulfonic acid as the catalyst, gave 6-methyl-2,3,4-trimethoxyphenol. In the last, Coenzyme Q0 was prepared through catalytic oxidation reaction with natrium dichromate as the oxidant. This route has easy to get raw materials and operating conditions moderate, pollution smaller advantages.Through experiments on each step of the reaction, and ultimately some improvements were made. The condition of the first step was moderate, it was a measurable reaction. By adding hydrogen peroxide to reduce the amount of bromine, and improving the reaction speed, lowering the cost of production, the yield was 96% above; The second step reaction choose CuI as a catalyst, improved the reaction yield, and further through the single factor experiment, The effects of the various factors were analyzed to obtain more satisfactory yield, The optimum conditions were: T=110℃, m(2,6-dibromide-p-cresol) : m(sodium methoxide) :m(CuI) =1:3.4 : 0.28, the yield of 2,6-dimethoxy-p-cresol was 91.8%. In the third-step reaction, using phase-transfer catalysis, 3,4,5-trimethoxytoluene was synthesized. The use of phase-transfer catalyst polyethylene glycol, to accelerate the reaction rate and increase the yield of the reaction. 6-methyl-2 ,3, 4 - trimethoxybenzaldehyde is synthesized by Vilsmeier- Haack reaction of the fourth step, optimized with the orthogonal design, the experiment results indicate that the most favorite reaction condition were: n(TMT):n(POCl3):n(DMF)=1:1.8:2.2, 70℃for 7h. Under optimum conditions, a yield of 93.2% with the purity of 98.5%. The last step ,first reaction of 6-methyl-2,3,4-trimethoxybenzaldehyde in the presence of p-toluenesulfonic acid with 30% hydrogen peroxide oxidation of 6-methyl-2,3,4 - trimethoxyphenol, then without separation, directly joining the sodium dichromate oxidation of coenzyme Q0 by recrystallization be crystal, and the goal of high purity products, the further reaction of the total yield of 74.4%.