| The Coenzyme Q10 (Co.Q10) also commonly called Ubiquinone, is a fat-soluble quinone compound, which exists widely in bodies of human, many animals and plants. It has the ability of transporting hydrogen in respiration system and plays an important role in physiological function. It has many kinds of activity in clinical use and became a main drug, health product, food additives and cosmetic for no harmful side-effect to human beings. So it has a huge market obviously.Solanesol became a focus for being material used to prepare many important compounds (including:Coenzyme10). A large number of solanesol is producted annually in China as a big country of consuming tobacco. However, there isn't too perfect synthetic route of Co.Q10 in China yet. It has significance to find an appropriate synthetic route and method to be used in industry.We designed two synthesis routes from solanesol through retro-synthetic analysis of Co.Q10 to fit to industrial preparation. And the new synthesis method—the microwave assistant synthesis in ironic liquid was used in one of routes, which hasn't been reported yet. Route A:C0Q10 was prepared by five steps reaction as addition, Friedel-Craft, Bielumn-duccep, Reduction and Oxidation. Contrast to the previous routes. The improved synthetic route was shorten two steps, and over yield is 27.5% by solanesol. Route B:C0Q10 was prepared by seven steps reaction as a-H substitution, hydration reaction, Wittig-Horner, Reduction to decaprenol, Reduction of CoQo, Friedel-Craft and Oxidation and over yield is 26.1%. We optimized the key conditions of each step in both routes, and get the optimal parameters and confirmed structure of almost compounds by NMR,IR or MS. The process is following:Route A:(1) The optimal condition of addition reaction:the reaction was catalysised by 0.1 eq. CuCl2 and reacting for 8hrs under N2 in 90℃. The yield of the product is 75%.(2) Friedel-Craft reaction:this is the most important step for the synthesis route of C0Q10. We improved the synthetic route by shorten two steps than previous one. In addition, the new optimal method was used in the step, which hasn't been reported yet. It is that solvent-free synthesis of F-C alkylation's product (1-(3-methyl-4-p-toluenesulfonyl-2-butene)-6-methyl-2,3,4,5-tereamethoxymethylbenzene) in ZnCl2·[Epy]BF4 ionic liquids under microwave irradiation. The yield is 70%.(3) The optimal condition of Bielumn-duccep coupling reaction:F-C alkylation product and solanesyl bromide as substrates, rations is 1.6:1, and were dissolved in THF, and catalysis by t-BuOK for 8hrs in-20℃, the yield is 68%.(4) The optimal condition of reduction reaction:the coupling reaction product was reduced by Na in EtOH and THF for 12 hrs in-5℃, the yield is 95%.(5) The optimal condition of oxidation reaction:the reduction product is oxidized in 4eq. CAN in 0℃, the yield is 51.5%.Route B:(1) The key optimal condition of bromide substitut reaction:the solanesol was substituted to be solanesyl bromide in 0℃by droped in PBr3 slowly, and the yield is 95.25%.(2) Under the catalysis of NaOEt, solanesyl bromide reacts with ethyl acetoacetate to produce intermediate product ester in room temperature. The best ratio Of M solanesyl bromide:M acetoacetate is 1:1.5, the yield is 91.22%.(3) The optimal condition of hydrolyze reaction, the carboxyl was removed from the intermediate ester in 15% NaOH in 80℃for 3hrs and the solanesylacetone was obtain by 91% yield.(4) The optimal condition of Wittig-Horner reaction:Msdanesyiacetone:M ester=1:5, the reaction reacts in 15℃for 3hrs in EtONa, and the best yield is 92.9%.(5) The optimal condition of reduction reaction:Decaprenoate is reduced to corresponding decaprenol with the help of Dibal-H reagent in absolute EtOEt at-78℃. The yield of this reaction is 83.34%.(6) The optimal condition of the last reaction:Mother nucleus Coenzyme Qo is hydrogenated and reduced to 2,3-dimethoxy-5-methyl-1,4-hydroquinone under the catalysis of 10%Pd/C. The yield of the reaction is 98%.Under the catalysis of BF3·EtOEt,2,3-dimethoxy-5-methyl-1,4-hydroquinone is heated and under goes condensation & coupling reaction with decaprenol to form HQio. HQ10 is further oxidized by FeCl3·6H2O to form Coenzyme Q10-The all over yields of these two steps is 42%.We designed two efficient synthetic routes to prepare CoQ10 it this paper, and the new synthesis method—the microwave assistant synthesis in ionic liquid was used in the route A. Then, we optimized every step of the two routes. There are some advantages:short route, new technology, easy to purification, mild reaction conditions, safe materials and low cost. The new technology has important value of industrial manufacture of CoQ10. |
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