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| Synthesis technology of 3-n-propyl-2, 4-dihydroxyacetophenone |
| LIU Yuan1, NAN Yun2, DAI Li-yan1, WANG Xiao-zhong1, CHEN Ying-qi11 |
1.Department of Chemical and Biological Engineering , Zhejiang University , Hangzhou 310027, China;
2. Zhejiang Sanhe Pharmachem Company Limited, Shangyu 312369, China |
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Abstract An improved process was reported to solve the problems such as low yield and high costs in the synthesis of 3-n-propyl-2, 4dihydroxyacetophenone, which is a key intermediate of Leukotriene receptor antagonist. The target compound was synthesized starting from m-dihydroxybenzene, via acylation, allylation, Claisen rearrangement and hydrogenation reduction. The optimal reaction conditions were as follows. The acylation reaction which used acetic acid as acylation agent and ZnCl2 as catalyst was carried out under reflux for 5 h, and 779% yield was obtained. The allylation reaction using allyl chloride as allylation reagent and NaBr、KI as catalyst was carried out at 40 °C for 2 h and continued at 70 °C for 14 h, to give 98.6% yield. In Claisen rearrangement carried out at 205 ℃ for 4.5 h, diphenyl ether was used as reaction solvent and NaCl was used as catalyst, and the yield was improved to 67.4%. In the final step, the hydrogenated reduction with Pd/C (w(Pd） is 5%) as catalyst was carried out at 45 ℃ for 6 h, and 88.6% yield was obtained. The process is much of industrial value because of high yield, cheap and available materials, and convenient operations. The structure of the main compounds was confirmed by 1HNMR、GC-MS and IR．
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Published: 01 September 2012
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3-正丙基-2, 4-二羟基苯乙酮的合成工艺
为解决白三烯受体拮抗剂中间体3-正丙基-2, 4-二羟基苯乙酮合成过程中收率低、成本高的问题,对其合成路线进行工艺改进,以间苯二酚为原料经过酰基化、烯丙基化、克莱森重排、加氢还原４步反应制得. 各步反应条件及收率如下：酰基化反应以醋酸为酰化剂在氯化锌催化下回流进行, 5 h, 收率77.9%; 以廉价的烯丙基氯为烯丙基化试剂, 溴化钠、碘化钾催化下进行烯丙基化反应, 40 ℃, 2 h, 70 ℃, 14 h, 收率986%; 克莱森重排反应改用二苯醚为反应溶剂, 并加入氯化钠催化, 提高了反应的专一性及收率, 205 ℃, 4.5 h, 收率67.4%; 加氢还原以钯碳（钯的质量分数为5%）为催化剂催化, 45 ℃, 6 h, 收率886%. 本工艺收率高、原料廉价易得、操作简便, 具有较好的工业应用价值. 主要化合物均经1HNMR、GC-MS、IR确证结构.
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