Synthesis of the Key Intermediate of Coenzyme Q10

Abstract

(2’E)-1-(3-methyl-4-p-toluenesulfonyl-2-butene)-6-methyl-2,3,4,5-tetramethoxybenzene (4) is the key intermediate in the synthesis of coenzyme Q10 via a coupling reaction with solanesyl bromide. In this paper, we report a simple and effective synthesis of compound 4, starting with the readily available and inexpensive precursors p-toluenesulfonyl chloride (TsCl) and isoprene to obtain (2E)-1-p-toluenesulfonyl-2-methyl-4-hydroxy-2-butene (3) by addition, esterification and hydrolysis. Application of the Friedel-Crafts alkylation to compound 3, followed by the addition of 2,3,4,5-tetramethoxytoluene (TeMT), assembled the two parts into compound 4. The key parameters of each reaction were optimized at the same time, and the four total operations needed to produced compound 4 had a 27.9% overall yield under the optimized conditions. The structures of the compounds were characterized by 1H-NMR, IR and MS. This alternative process has the potential to be used for large-scale process.

Keywords

• p-toluenesulfonyl chloride
• isoprene
• 2,3,4,5-tetramethoxytoluene
• (2’E)-1-(3-methyl-4-p-toluenesulfonyl-2-butene)-6-methyl-2,3,4,5-tetramethoxybenzene