化工进展 ›› 2022, Vol. 41 ›› Issue (11): 6053-6060.DOI: 10.16085/j.issn.1000-6613.2022-0153
收稿日期:
2022-01-24
修回日期:
2022-03-25
出版日期:
2022-11-25
发布日期:
2022-11-28
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。
FANG Cong(), LIU Yixue, LI Sifang()
Received:
2022-01-24
Revised:
2022-03-25
Online:
2022-11-25
Published:
2022-11-28
Contact:
LI Sifang
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%。
中图分类号:
方聪, 刘怡雪, 黎四芳. 爱德万甜中间体3-羟基-4-甲氧基肉桂醛的合成[J]. 化工进展, 2022, 41(11): 6053-6060.
FANG Cong, LIU Yixue, LI Sifang. Synthesis of 3-hydroxy-4-methoxy cinnamaldehyde as intermediate of advantame[J]. Chemical Industry and Engineering Progress, 2022, 41(11): 6053-6060.
因素 | 水平 | ||
---|---|---|---|
-1 | 0 | 1 | |
A 反应时间/h | 8 | 12 | 16 |
B 反应温度/℃ | 5 | 10 | 15 |
C NaOH浓度/mol·L-1 | 0.14 | 0.18 | 0.22 |
D 异香兰素与乙酸乙烯摩尔比 | 1∶1.5 | 1∶2 | 1∶2.5 |
表1 响应面实验因素水平设计
因素 | 水平 | ||
---|---|---|---|
-1 | 0 | 1 | |
A 反应时间/h | 8 | 12 | 16 |
B 反应温度/℃ | 5 | 10 | 15 |
C NaOH浓度/mol·L-1 | 0.14 | 0.18 | 0.22 |
D 异香兰素与乙酸乙烯摩尔比 | 1∶1.5 | 1∶2 | 1∶2.5 |
序列 | 因素 | 收率/% | ||||
---|---|---|---|---|---|---|
A:反应时间 | B:反应温度 | C:NaOH 浓度 | D:异香兰素与乙酸乙烯摩尔比 | 实际值 | 预测值 | |
1 | -1 | 0 | 1 | 0 | 37.94 | 38.92 |
2 | 0 | -1 | 1 | 0 | 31.55 | 29.23 |
3 | 1 | -1 | 0 | 0 | 36.61 | 37.56 |
4 | -1 | -1 | 0 | 0 | 34.17 | 35.31 |
5 | 1 | 1 | 0 | 0 | 30.57 | 30.59 |
6 | -1 | 1 | 0 | 0 | 28.88 | 29.09 |
7 | 0 | 1 | -1 | 0 | 25.36 | 25.66 |
8 | -1 | 0 | -1 | 0 | 41.13 | 40.71 |
9 | 0 | 0 | 0 | 0 | 69.23 | 71.44 |
10 | 0 | 0 | 0 | 0 | 71.25 | 71.44 |
11 | 0 | 0 | 0 | 0 | 70.98 | 71.44 |
12 | 1 | 0 | -1 | 0 | 43.95 | 43.83 |
13 | 0 | 1 | 1 | 0 | 23.25 | 22.44 |
14 | 0 | 0 | 0 | 0 | 72.54 | 71.44 |
15 | 0 | 0 | 0 | 0 | 73.21 | 71.44 |
16 | 0 | -1 | -1 | 0 | 33.29 | 32.07 |
17 | 1 | 0 | 1 | 0 | 39.59 | 40.21 |
18 | -1 | 0 | 0 | 1 | 45.82 | 44.61 |
19 | 0 | 1 | 0 | 1 | 28.79 | 28.75 |
20 | 0 | 0 | -1 | 1 | 40.77 | 41.27 |
21 | 0 | -1 | 0 | 1 | 33.98 | 34.52 |
22 | 1 | 0 | 0 | 1 | 46.78 | 46.12 |
23 | 0 | 0 | 1 | 1 | 37.02 | 37.89 |
24 | 0 | 0 | -1 | -1 | 39.11 | 39.40 |
25 | 0 | -1 | 0 | -1 | 32.93 | 33.83 |
26 | 0 | 0 | 1 | -1 | 36.07 | 36.73 |
27 | 1 | 0 | 0 | -1 | 45.78 | 44.97 |
28 | 0 | 1 | 0 | -1 | 26.07 | 26.40 |
29 | -1 | 0 | 0 | -1 | 44.10 | 42.73 |
表2 响应面实验结果表
序列 | 因素 | 收率/% | ||||
---|---|---|---|---|---|---|
A:反应时间 | B:反应温度 | C:NaOH 浓度 | D:异香兰素与乙酸乙烯摩尔比 | 实际值 | 预测值 | |
1 | -1 | 0 | 1 | 0 | 37.94 | 38.92 |
2 | 0 | -1 | 1 | 0 | 31.55 | 29.23 |
3 | 1 | -1 | 0 | 0 | 36.61 | 37.56 |
4 | -1 | -1 | 0 | 0 | 34.17 | 35.31 |
5 | 1 | 1 | 0 | 0 | 30.57 | 30.59 |
6 | -1 | 1 | 0 | 0 | 28.88 | 29.09 |
7 | 0 | 1 | -1 | 0 | 25.36 | 25.66 |
8 | -1 | 0 | -1 | 0 | 41.13 | 40.71 |
9 | 0 | 0 | 0 | 0 | 69.23 | 71.44 |
10 | 0 | 0 | 0 | 0 | 71.25 | 71.44 |
11 | 0 | 0 | 0 | 0 | 70.98 | 71.44 |
12 | 1 | 0 | -1 | 0 | 43.95 | 43.83 |
13 | 0 | 1 | 1 | 0 | 23.25 | 22.44 |
14 | 0 | 0 | 0 | 0 | 72.54 | 71.44 |
15 | 0 | 0 | 0 | 0 | 73.21 | 71.44 |
16 | 0 | -1 | -1 | 0 | 33.29 | 32.07 |
17 | 1 | 0 | 1 | 0 | 39.59 | 40.21 |
18 | -1 | 0 | 0 | 1 | 45.82 | 44.61 |
19 | 0 | 1 | 0 | 1 | 28.79 | 28.75 |
20 | 0 | 0 | -1 | 1 | 40.77 | 41.27 |
21 | 0 | -1 | 0 | 1 | 33.98 | 34.52 |
22 | 1 | 0 | 0 | 1 | 46.78 | 46.12 |
23 | 0 | 0 | 1 | 1 | 37.02 | 37.89 |
24 | 0 | 0 | -1 | -1 | 39.11 | 39.40 |
25 | 0 | -1 | 0 | -1 | 32.93 | 33.83 |
26 | 0 | 0 | 1 | -1 | 36.07 | 36.73 |
27 | 1 | 0 | 0 | -1 | 45.78 | 44.97 |
28 | 0 | 1 | 0 | -1 | 26.07 | 26.40 |
29 | -1 | 0 | 0 | -1 | 44.10 | 42.73 |
方差来源 | 平方和 | 自由度 | 均方 | F | P | 显著性 |
---|---|---|---|---|---|---|
回归方程 | 6249.78 | 14 | 446.41 | 223.75 | < 0.0001 | + + |
A | 10.53 | 1 | 10.53 | 5.28 | 0.0376 | |
B | 130.75 | 1 | 130.75 | 65.53 | < 0.0001 | + + |
C | 27.57 | 1 | 27.57 | 13.82 | 0.0023 | + |
D | 6.90 | 1 | 6.90 | 3.46 | 0.0841 | |
AB | 0.14 | 1 | 0.14 | 0.070 | 0.7945 | |
AC | 0.34 | 1 | 0.34 | 0.17 | 0.6850 | |
AD | 0.13 | 1 | 0.13 | 0.065 | 0.8025 | |
BC | 0.034 | 1 | 0.034 | 0.017 | 0.8977 | |
BD | 0.70 | 1 | 0.70 | 0.35 | 0.5638 | |
CD | 0.13 | 1 | 0.13 | 0.063 | 0.8052 | |
A2 | 979.04 | 1 | 979.04 | 490.72 | < 0.0001 | + + |
B2 | 4391.39 | 1 | 4391.39 | 2201.09 | < 0.0001 | + + |
C2 | 2118.43 | 1 | 2118.43 | 1061.82 | < 0.0001 | + + |
D2 | 1372.84 | 1 | 1372.84 | 688.11 | < 0.0001 | + + |
残差 | 27.93 | 14 | 2.00 | — | — | |
失拟项 | 18.46 | 10 | 1.85 | 0.78 | 0.6603 | |
纯误差 | 9.47 | 4 | 2.37 | — | — | |
总和 | 6277.71 | 28 | — | — | — |
表3 方差分析
方差来源 | 平方和 | 自由度 | 均方 | F | P | 显著性 |
---|---|---|---|---|---|---|
回归方程 | 6249.78 | 14 | 446.41 | 223.75 | < 0.0001 | + + |
A | 10.53 | 1 | 10.53 | 5.28 | 0.0376 | |
B | 130.75 | 1 | 130.75 | 65.53 | < 0.0001 | + + |
C | 27.57 | 1 | 27.57 | 13.82 | 0.0023 | + |
D | 6.90 | 1 | 6.90 | 3.46 | 0.0841 | |
AB | 0.14 | 1 | 0.14 | 0.070 | 0.7945 | |
AC | 0.34 | 1 | 0.34 | 0.17 | 0.6850 | |
AD | 0.13 | 1 | 0.13 | 0.065 | 0.8025 | |
BC | 0.034 | 1 | 0.034 | 0.017 | 0.8977 | |
BD | 0.70 | 1 | 0.70 | 0.35 | 0.5638 | |
CD | 0.13 | 1 | 0.13 | 0.063 | 0.8052 | |
A2 | 979.04 | 1 | 979.04 | 490.72 | < 0.0001 | + + |
B2 | 4391.39 | 1 | 4391.39 | 2201.09 | < 0.0001 | + + |
C2 | 2118.43 | 1 | 2118.43 | 1061.82 | < 0.0001 | + + |
D2 | 1372.84 | 1 | 1372.84 | 688.11 | < 0.0001 | + + |
残差 | 27.93 | 14 | 2.00 | — | — | |
失拟项 | 18.46 | 10 | 1.85 | 0.78 | 0.6603 | |
纯误差 | 9.47 | 4 | 2.37 | — | — | |
总和 | 6277.71 | 28 | — | — | — |
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