Chemical Industry and Engineering Progress ›› 2022, Vol. 41 ›› Issue (11): 6053-6060.DOI: 10.16085/j.issn.1000-6613.2022-0153

• Fine chemicals • Previous Articles     Next Articles

Synthesis of 3-hydroxy-4-methoxy cinnamaldehyde as intermediate of advantame

FANG Cong(), LIU Yixue, LI Sifang()   

  1. College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, China
  • Received:2022-01-24 Revised:2022-03-25 Online:2022-11-28 Published:2022-11-25
  • Contact: LI Sifang

爱德万甜中间体3-羟基-4-甲氧基肉桂醛的合成

方聪(), 刘怡雪, 黎四芳()   

  1. 厦门大学化学化工学院,福建 厦门 361005
  • 通讯作者: 黎四芳
  • 作者简介:方聪(1993—),男,硕士研究生,研究方向为精细化工。E-mail:congfang@stu.xmu.edu.cn

Abstract:

3-Hydroxy-4-methoxy cinnamaldehyde is an important intermediate for the preparation of advantame, which is a novel dipeptide sweetener with super-high potency. At present, this intermediate is mainly synthesized by Aldol condensation reaction of isovanillin and acetaldehyde in the presence of strong base. However, since acetaldehyde is prone to self-condensation, there are problems such as harsh reaction conditions and low yield of 3-hydroxy-4-methoxy cinnamaldehyde. In this paper, a new process for preparation of 3-hydroxy-4-methoxy cinnamaldehyde by using vinyl acetate as a reactant in place of acetaldehyde to react with isovanillin was studied. The influences of reaction temperature, reaction time, NaOH dosage and molar ratio of isovanillin to vinyl acetate on the reaction were investigated by single factor experiments. On the basis of the single factor experiments, the response surface optimization was carried out. Results showed that the yield of 3-hydroxy-4-methoxy cinnamaldehyde was 71.44%±2.21% under optimal conditions: NaOH concentration of 4.5mol/L, reaction temperature of 10℃, reaction time of 12h and the molar ratio of isovanillin to vinyl acetate of 1∶2. In order to further improve the product yield, the strengthening effect of adding a phase transfer catalyst to the reaction system was explored. It was found that PEG-200 had a significant catalytic effect on the reaction, and the yield of 3-hydroxy-4-methoxy cinnamaldehyde achieved 83.12%±2.18%.

Key words: synthesis, 3-hydroxy-4-methoxycinnamaldehyde, vinyl acetate, catalysis, optimization

摘要:

3-羟基-4-甲氧基肉桂醛是制备新型的二肽超高甜度甜味剂爱德万甜的重要中间体。目前制备该中间体的主要方法是通过异香兰素与乙醛在强碱存在下进行羟醛缩合反应,但由于乙醛容易发生自缩合反应从而存在反应条件极为苛刻和3-羟基-4-甲氧基肉桂醛收率低等问题,本文以乙酸乙烯作为反应物替代乙醛与异香兰素发生反应合成3-羟基-4-甲氧基肉桂醛,采用单因素实验考察了反应温度、反应时间、NaOH浓度和异香兰素与乙酸乙烯配比对该反应的影响,并在此基础上进行了响应面优化。在优化的反应条件(NaOH浓度4.5mol/L,反应温度10℃,反应时间12h,异香兰素与乙酸乙烯摩尔比1∶2)下,3-羟基-4-甲氧基肉桂醛收率为71.44%±2.21%。为了进一步提高产品收率,探索了添加相转移催化剂对该反应的强化作用,发现PEG-200对强化该反应有显著作用,3-羟基-4-甲氧基肉桂醛收率可达83.12%±2.18%。

关键词: 合成, 3-羟基-4-甲氧基肉桂醛, 乙酸乙烯, 催化, 优化

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