Study On The Synthesis Of Coenzyme Q₁₀

Coenzyme Q is an effective pharmaceutical. In this thesis, we have studied on the synthesis of coenzyme. Coenzyme Q0 is prepared from p-cresol in a four-step procedure. Bromination of p-cresol provided 2,6-dibromo-4-methylphenol, copper-catalyzed methoxylation of the 2,6-dibromo-4-methylphenol, methylation with dimethylsulfate subsequently are employed to give 3,4,5-trimethoxytoluene. Then 3,4,5-trimethoxytoluene is oxidized by 30% H2O2 in the solution of CH3COOH. 1-phenylsulfonyl-2-methyl-4-chloro-2-butene is easily obtained by the reaction of isoprene and benzenesulfonyl chloride in the presence of copper(â… ) chloride and triethylamine hydrochloride. The reaction conditions are optimized with the yield of 52.7%. Solanesol (75%) was purified with silica gel column chromatography. The optimal separation conditions are as following: sample/ silica gel=1/30(weight), dilution agent is ether/ petroleum ether 1/10(v/v); dilution rate 4-5ml/min. Solanesol can react with PBr3 easily in the presence of pyridine to give solanesyl bromide with the yield of 94%.Coenzyme Q10 is synthesized via the grignard reaction of 1-phenylsulfonyl-2-methyl-4-chloro-2-butene and 6-bromo-2,3-dimethoxy-5-methylbenzoquinone which is prepared by brominatyion of coenzyme Q0 and reduction by Na2S2O4 resepectively. Unfortunately, no prospective product is got. Coenzyme Q9 can be obtained through the condensation of solanesol with reduced coenzyme Q0 in the presence of boron trifluoride etherate; but the yield is very low.