哌拉西林非均相合成反应动力学的研究

doi:10.11949/0438-1157.20211095

摘要/Abstract

摘要：

哌拉西林是一种重要的抗生素，它是利用氨苄西林水溶液和4-乙基-2，3-二氧-1-哌嗪甲酰氯(EDPC)的二氯甲烷溶液在油水界面处反应得到的。利用恒界面池研究界面表观合成反应动力学，确定符合一级反应动力学模型。详细讨论了搅拌速率、比界面积、pH、温度对反应速率的影响，实验结果表明，当搅拌速率大于250 r/min时出现与搅拌强度无关的化学反应控制“坪区”，在“坪区”下，反应速率常数随比界面积、pH、温度增大而增大。通过温度与反应速率常数的关系，得到反应的动力学数据与热力学数据，并通过与密度泛函理论(DFT)结合推导反应机理。

关键词: 恒界面池, 界面, 多相反应, N-酰基化反应, 反应动力学, 计算机模拟

Abstract:

Piperacillin is an important antibiotic, which can be synthesized by the reaction of ampicillin aqueous solution and methylene chloride solution of 4-ethyl-2, 3-dioxy-1-piperazine formyl chloride (EDPC) at the oil-water interface. In this paper, the constant interface cell is used to study the apparent synthesis reaction kinetics at the interface, and it is determined that it conforms to the first-order reaction kinetic model. The effects of stirring rate, specific boundary area, pH and temperature on the reaction rate were discussed in details. The experimental results showed that when the stirring rate was greater than 250 r/min, there is a "flat zone" of chemical reaction control which is independent of the stirring strength. Under the "flat zone", the reaction rate constant increases with the increase of specific boundary area, pH and temperature. Through the relationship between temperature and reaction rate constant, the kinetic and thermodynamic data of the reaction were obtained, and then the reaction mechanism was deduced by combining with density functional theory (DFT).

Key words: constant interface cell, interface, multiphase reaction, N-acylation, reaction kinetics, computer simulation

中图分类号:

TQ 465.1

谢煜, 王玉军. 哌拉西林非均相合成反应动力学的研究[J]. 化工学报, 2021, 72(12): 6254-6261.

Yu XIE, Yujun WANG. A study on kinetics of heterogeneous synthesis of piperacillin[J]. CIESC Journal, 2021, 72(12): 6254-6261.

图/表 14

图1 哌拉西林合成路线

Fig.1 The synthetic pathway of piperacillin

图2 实验装置示意图

Fig.2 Schematic diagram of experimental device

表1 流动相梯度

Table 1 Mobile phase gradient

时间/min	流动相A/%	流动相B/%
0	90	10
5	85	15
10	65	35
35	55	45
60	35	65
65	90	10
75	90	10

图3 不同转速下水相中哌拉西林浓度随时间的变化

Fig.3 Change of piperacillin concentration in aqueous phase with time at different rotational speeds

图4 不同初始浓度下哌拉西林含量随时间变化

Fig.4 Change of piperacillin content with time at different initial concentrations

图5 不同初始浓度下一级反应动力学拟合图

Fig.5 Fitting diagram of first-order reaction kinetics at different initial concentrations

图6 不同界面积下反应速率常数k的拟合图

Fig.6 Fitting diagram of reaction rate constant k under different boundary areas

图7 比界面积对反应速率常数k的影响

Fig.7 The effect of specific interfacial area on the rate constant k

图8 不同pH下反应速率常数k的拟合图

Fig.8 Fitting diagram of reaction rate constant k at different pH

图9 pH对反应速率常数k的影响

Fig.9 The effect of pH on the reaction rate constant k

图10 不同温度下反应速率常数k的拟合图

Fig.10 Fitting diagram of reaction rate constant k at different temperatures

图11 温度对反应速率常数k的影响

Fig.11 Effect of temperature on the reaction rate constant k

图12 ln(k/T)-T-1拟合图

Fig.12 Fitting diagram of ln(k/T)-T-1

图13 氨苄西林与EDPC合成哌拉西林过程中自由能变化及中间体、过渡态结构

Fig.13 Free energy changes, intermediate and transition state structures during the synthesis of piperacillin with ampicillin and EDPC

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