Synthesis And Optimization Of Coenzyme Q₀

Coenzyme Q is known for its clinical activities. Coenzyme Q₀(2,3-Dimethoxy-5-methyl-1,4-p-benzoquinone) is an important medical intermediate of CoenzymeQ₁₀. Based on the literature search,a commercial and practical synthesis way with p-cresol as start material is chosen. Coenzyme Q₀ and intermediate of Coenzyme Q₁₀ l-(Benzensulfonyl)-2-methyl-4-chloro-2-butene are prepared by reactions such as bromination, methoxylation, methylation, oxidation and so on.In the preparation of Coenzyme Q₀, we synthesize 3,4,5-trimethoxy-toluene and 2,3,4,5-tetramethoxy-toluene with p-cresol as start material firstly. After that, Coenzyme Q₀ was prepared with these two materials as start material respectively by oxidation. By comparison,the way with 2,3,4,5-tetramethoxy-toluene as start material is better. The route have some merits as following: cheap and available material,short steps,mild reaction conditions and simple operation. After many experiments, we have obtained a better technology for preparation of 3,4,5-trimethoxy-toluene. The better reaction conditions of the technology as following: the ratio of 2,6 -dimetoxy-4-methylphenol to potassium hydroxide and dimethyl sulfate is 1:0.85:0.15 (quality ratio),reaction temperature is 90℃,reaction time is 3 hours. Its yield is 91.5%. Trans-l-(Benzensulfonyl)-2-methyl-4-chloro-2-butene,a key intermediate for synthesizing coenzyme Q₁₀, was synthesized by addition of benzensulfonyl chloride to isoprene in autoclave with cupric chloride as catalyst and teiethylammine hydrochloride as phase transfer catalyst.By comparison with the original literature,many improvements are made on technology, production cost, operation and so on.