维生素U生产工艺优化及其热分解机理

doi:10.16085/j.issn.1000-6613.2023-1465

化工进展 ›› 2024, Vol. 43 ›› Issue (9): 5157-5167.DOI: 10.16085/j.issn.1000-6613.2023-1465

• 生物与医药化工 • 上一篇

维生素U生产工艺优化及其热分解机理

王禹程¹(), 郭雄², 栾昕奇¹, 周健², 李想¹, 幸林广², 周雪芸², 刘颖², 汪德勇¹, 吴雪娟², 潘琦¹, 刘建新², 赵祯霞¹, 赵钟兴¹()

^1.广西大学化学化工学院广西高校低碳绿色化工新技术重点实验室，广西南宁 530004
^2.广西南宁百会药业集团有限公司，广西南宁 5330032

收稿日期:2023-08-22 修回日期:2023-10-27 出版日期:2024-09-15 发布日期:2024-09-30
通讯作者: 赵钟兴
作者简介:王禹程（1998—），男，硕士研究生，研究方向为化工工艺。E-mail：1422868013@qq.com。
基金资助:
国家自然科学基金(22172039);广西自然科学基金(2022GXNSFAA035464)

Production process optimization of vitamin U and its thermal decomposition mechanism

WANG Yucheng¹(), GUO Xiong², LUAN Xinqi¹, ZHOU Jian², LI Xiang¹, XING Linguang², ZHOU Xueyun², LIU Ying², WANG Deyong¹, WU Xuejuan², PAN Qi¹, LIU Jianxin², ZHAO Zhenxia¹, ZHAO Zhongxing¹()

^1.Key Laboratory of New Low-Carbon Green Chemical Technology, Education Department of Guangxi, School of Chemistry and Chemical Engineering, Guangxi University, Nanning 530004, Guangxi, China
^2.Guangxi Nanning Baihui Pharmaceutical Industry Group Company Limited, Nanning 530032, Guangxi, China

Received:2023-08-22 Revised:2023-10-27 Online:2024-09-15 Published:2024-09-30
Contact: ZHAO Zhongxing

摘要/Abstract

摘要：

为提高维生素U收率和最终产品纯度，并减少其热分解产物对最终产品质量的影响，对维生素U生产工艺优化和热分解产物分析。首先，通过对维生素U合成、脱色和浓缩等3个工序的优化，得到最佳维生素U生产条件为：合成温度为54℃，蛋氨酸与氯甲烷的投料摩尔比为1∶2.6，脱色时活性炭用量为2g/L，脱色时间为8min，浓缩温度控制在55℃，浓缩时间为8h。然后再对维生素U的热解产物进行高效液相色谱-质谱联用和气相色谱-质谱联用分析，确定了维生素U在水溶液中的主要热分解产物组成和可能的降解路径。最后，通过分子模拟计算印证甲醇可作为精制溶剂去除维生素U生产过程中产生的热解产物。优化后的工艺平均收率提高了8.5百分点，平均纯度提高了0.8百分点，平均误差分别减少了5.1百分点和0.33百分点，平均熔程减小了0.8℃，工艺稳定性显著提升，所得维生素U的纯度在满足国家标准的基础上进一步提高。该工作对进一步优化维生素U生产工艺具有借鉴意义。

关键词: 维生素U, 生产, 分解产物, 分子模拟, 优化

Abstract:

In order to improve the yield of vitamin U and the purity of the final product and reduce the influence of the thermal decomposition products on the quality of the final product, the production process of vitamin U was optimized, and the thermal decomposition products were analyzed. Firstly, through the optimization of the three processes of vitamin U, including synthesis, decolorization, and concentration, the optimal production conditions of vitamin U were obtained as follows: The synthesis temperature was 54℃, the molar ratio of methionine to chloromethane was 1∶2.6, the amount of activated carbon was 2g/L, the decolorization time was 8min, the concentration temperature was controlled at 55℃, and the concentration time was 8h. Then the thermal decomposition products of vitamin U were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and gas chromatography-mass spectrometry (GC-MS). The main thermal decomposition products compositions and the possible degradation pathways of vitamin U in an aqueous solution were determined. Molecular simulation calculations corroborated that methanol could be used as a refining solvent to remove thermal decomposition products generated during vitamin U production. The average yield of the optimized process was increased by 8.5 percentage points, the average purity was increased by 0.8 percentage points, the average error was reduced by 5.1 percentage points and 0.33 percentage points, respectively, the average melting range was reduced by 0.8℃, the stability of the process was significantly improved, and the purity of the vitamin U was further improved on the basis of meeting the national standards. This work has reference significance for further optimization of the vitamin U production process.

Key words: vitamin U, production, decomposition products, molecular simulation, optimization

中图分类号:

TQ466.7

王禹程, 郭雄, 栾昕奇, 周健, 李想, 幸林广, 周雪芸, 刘颖, 汪德勇, 吴雪娟, 潘琦, 刘建新, 赵祯霞, 赵钟兴. 维生素U生产工艺优化及其热分解机理[J]. 化工进展, 2024, 43(9): 5157-5167.

WANG Yucheng, GUO Xiong, LUAN Xinqi, ZHOU Jian, LI Xiang, XING Linguang, ZHOU Xueyun, LIU Ying, WANG Deyong, WU Xuejuan, PAN Qi, LIU Jianxin, ZHAO Zhenxia, ZHAO Zhongxing. Production process optimization of vitamin U and its thermal decomposition mechanism[J]. Chemical Industry and Engineering Progress, 2024, 43(9): 5157-5167.

图/表 12

参考文献 14

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次数	优化前^①			优化后
次数	总收率/%	产品纯度/%	熔点/℃	总收率/%	产品纯度/%	熔点/℃
1	76.5	98.2	134.2~136.8	81.7	99.4	134.5~135.8
2	68.9	98.7	134.1~135.9	83.2	99.6	134.3~135.7
3	73.2	98.6	134.1~136.2	80.6	99.1	134.1~135.7
4	71.2	98.2	134.2~136.5	82.5	99.5	134.2~135.3
5	78.3	99.1	134.5~136.1	81.4	99.3	134.5~135.4
平均值	74.4±6.7	98.6±0.55	2.1（熔程）	82.9±1.6	99.4±0.22	1.3（熔程）

次数	优化前^①			优化后
次数	总收率/%	产品纯度/%	熔点/℃	总收率/%	产品纯度/%	熔点/℃
1	76.5	98.2	134.2~136.8	81.7	99.4	134.5~135.8
2	68.9	98.7	134.1~135.9	83.2	99.6	134.3~135.7
3	73.2	98.6	134.1~136.2	80.6	99.1	134.1~135.7
4	71.2	98.2	134.2~136.5	82.5	99.5	134.2~135.3
5	78.3	99.1	134.5~136.1	81.4	99.3	134.5~135.4
平均值	74.4±6.7	98.6±0.55	2.1（熔程）	82.9±1.6	99.4±0.22	1.3（熔程）

编号	模式	保留时间/min	加合离子	分子式	质荷比(m/z)	名称
U	Neg	0.85	[M-H-C₄H₁₀ClS+Cl₃]^-, [M-H C₄H₁₀ClS+Cl₄]^-	C₆H₁₄ClNO₂S	160.84 197.81	维生素U
P1 P2	Poz	0.85	[M+H-H₂O]⁺ [M+H]⁺	C₄H₉NO₃	102.06 120.07	高丝氨酸、苏氨酸
P1 P2	Neg	0.85 1.12 1.37 3.72	[M-C₂H₅-H]^- [M-H]^-	C₄H₉NO₃	89.02 118.05	高丝氨酸、苏氨酸
P3	Poz	1.47	[M+H]⁺	C₆H₁₃NO₂S	150.06	四氢噻吩-2-羧酸
P4	Poz	1.06	[M+H]⁺	C₅H₈O₂S	164.07	乙硫氨酸
P5	Poz	1.02	[M+H]⁺	C₅H₁₁NO₃S	166.05	蛋氨酸亚砜
P6	Neg	1.03	[M-H]^- [M+Cl]^-	C₅H₁₁NO₂S	148.04 184.02	蛋氨酸
P6	Poz	1.03	[M+H-C₂H₄O₃]⁺	C₅H₁₁NO₂S	74.06	蛋氨酸
P7	Poz	0.57	[M+H]⁺	C₅H₁₁NO₃	134.08	高丝氨酸甲酯
P8	Neg	1.12 1.37	[M-H]^-	C₉H₁₈N₂O₄S	249.09	苏氨酸-蛋氨酸
P9 P10	Neg	9.82	[M-H]^-	C₄H₈ClNO₂	134.90	4-Cl-2-氨基丁酸 3-Cl-2-氨基丁酸

编号	模式	保留时间/min	加合离子	分子式	质荷比(m/z)	名称
U	Neg	0.85	[M-H-C₄H₁₀ClS+Cl₃]^-, [M-H C₄H₁₀ClS+Cl₄]^-	C₆H₁₄ClNO₂S	160.84 197.81	维生素U
P1 P2	Poz	0.85	[M+H-H₂O]⁺ [M+H]⁺	C₄H₉NO₃	102.06 120.07	高丝氨酸、苏氨酸
P1 P2	Neg	0.85 1.12 1.37 3.72	[M-C₂H₅-H]^- [M-H]^-	C₄H₉NO₃	89.02 118.05	高丝氨酸、苏氨酸
P3	Poz	1.47	[M+H]⁺	C₆H₁₃NO₂S	150.06	四氢噻吩-2-羧酸
P4	Poz	1.06	[M+H]⁺	C₅H₈O₂S	164.07	乙硫氨酸
P5	Poz	1.02	[M+H]⁺	C₅H₁₁NO₃S	166.05	蛋氨酸亚砜
P6	Neg	1.03	[M-H]^- [M+Cl]^-	C₅H₁₁NO₂S	148.04 184.02	蛋氨酸
P6	Poz	1.03	[M+H-C₂H₄O₃]⁺	C₅H₁₁NO₂S	74.06	蛋氨酸
P7	Poz	0.57	[M+H]⁺	C₅H₁₁NO₃	134.08	高丝氨酸甲酯
P8	Neg	1.12 1.37	[M-H]^-	C₉H₁₈N₂O₄S	249.09	苏氨酸-蛋氨酸
P9 P10	Neg	9.82	[M-H]^-	C₄H₈ClNO₂	134.90	4-Cl-2-氨基丁酸 3-Cl-2-氨基丁酸

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维生素U生产工艺优化及其热分解机理

Production process optimization of vitamin U and its thermal decomposition mechanism

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