Please wait a minute...
浙江大学学报(工学版)
J4  2012, Vol. 46 Issue (9): 1697-1701    DOI: 10.3785/j.issn.1008-973X.2012.09.023
化学工程     
3-正丙基-2, 4-二羟基苯乙酮的合成工艺
刘员1, 南云2, 戴立言1, 王晓钟1, 陈英奇1
1.浙江大学 化学工程与生物工程学系， 浙江 杭州 310027；2.浙江新三和医药化工
股份有限公司, 浙江 上虞 312369
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
 全文: PDF  HTML
摘要：

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986%; 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886%. 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1HNMR、GC-MS、IR确证结构.
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, 4dihydroxyacetophenone, 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 779% 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 1HNMR、GC-MS and IR．
出版日期: 2012-09-01
:  TQ 244.5  
基金资助:

国家自然科学基金资助项目（21176213）； 浙江省重点科技创新团队——绿色制药工艺科技创新团队资助项目（2010R50043）.
通讯作者: 戴立言, 男, 副教授.     E-mail: dailiyan@zju.edu.cn
作者简介: 刘员 (1988-）, 女, 硕士生, 从事医药中间体的合成研究. E-mail: 20928170@zju.edu.cn
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　

引用本文:

刘员, 南云, 戴立言, 王晓钟, 陈英奇. 3-正丙基-2, 4-二羟基苯乙酮的合成工艺[J]. J4, 2012, 46(9): 1697-1701.

LIU Yuan, NAN Yun, DAI Li-yan, WANG Xiao-zhong, CHEN Ying-qi. Synthesis technology of 3-n-propyl-2, 4-dihydroxyacetophenone. J4, 2012, 46(9): 1697-1701.

链接本文:

http://www.zjujournals.com/eng/CN/10.3785/j.issn.1008-973X.2012.09.023    或    http://www.zjujournals.com/eng/CN/Y2012/V46/I9/1697

［1］ MAGNUS N A, ANZEVENO P B, COFFEY D C, et al. Optimized catalytic enantioselective aryl transfer process gives access to mGlu2 receptor potentiators ［J］. Organic Process Research and Development, 2007, 11: 560-567．
［2］ AICHER T D, BENESH D R, BLANCOPILLADO M, et al. Potentiators of glutamate receptors: WO, 2006207860 ［P］. 2006-06-01．
［3］ FRENETTE R, GAUTHIER J Y, YOUNG R N, et al. Stereoselective synthesis of leukotriene antagonists: US, 4857659 ［P］. 1989-08-15．
［4］ DIXIT M, TRIPATHI B K, SRIVASTAVA A K, et al. Synthesis of functionalized acetophenones as protein tyrosine phosphatase 1B inhibitors ［J］. Bioorganic and Medicinal Chemistry Letters, 2005, 15(14): 3394-3397．
［5］ GOZZO F C, FERNANDES S A, RODRIGUES D C, et al. Regioselectivity in aromatic claisen rearrangements ［J］. The Journal of Organic Chemistry, 2003, 68: 5493-5499．
［6］ ALAM S, SARKAR Z, IALAM A. Synthesis and studies of antibacterial activity of pongaglabol ［J］. Journal of the Chemical Society, 2004, 116(1): 29-32．
［7］ RAO R R, TIWARI A K, REDDY P P, et al. New furanoflavanoids, intestinal αglucosidase inhibitory and freeradical(DPPH) scavenging activity from antihyperglycemic root extract of Derris indica(Lam.) ［J］. Bioorganic and Medicinal Chemistry, 2009, 17(14): 5170-5175．
［8］ 廖头根, 汪秋安, 方伟琴, 等. 新型查尔酮类化合物的合成及其生物活性研究［J］. 有机化学, 2006, 26(5): 685-689．
LIAO Tougen, WANG Qiuan, FANG Weiqin, et al. Studies on the synthesis of novel chalcone and biological activity ［J］. Chinese Journal of Organic Chemistry, 2006, 26(5): 685-689．
［9］ 马良, 陈万锁, 鲁波, 等. 手性α烯丙基苯甲醇的立体选择性合成研究［J］. 浙江大学学报：工学版, 2006, 40(1): 162-166．
MA Liang, CHEN Wansuo, LU Bo, et al．Stereoselective synthesis of chiral αallylbenzyl alcohol ［J］. Journal of Zhejiang University ：Engineering Science, 2006, 40(1): 162-166.
No related articles found!