青霉胺结晶热力学及拆分工艺研究

doi:10.11949/0438-1157.20201162

摘要/Abstract

摘要：

实验测定了DL-及D-青霉胺在273.15~333.15 K、不同质量比乙醇-水混合溶剂中的溶解度，以此确定了合适的结晶溶剂比例。绘制了273.15、283.15、293.15、303.15、313.15和323.15 K下青霉胺溶解度曲线。测定了D-和DL-青霉胺以及ee值为87%溶液的介稳区宽度。研究了不同ee值饱和溶液（饱和温度为313.15 K）在不同初始过冷度下起始成核情况及ee值为87%的饱和溶液在不同初始过冷度和晶种量下的等温结晶过程。最后考察了不同降温速率、晶种量对ee值为87%原料的结晶拆分情况。结果表明，对于等温结晶过程，随着结晶进行，产品ee值下降，且初始过冷度越大、晶种加入量越多，ee>99%的产品收率越高；对于降温结晶过程，产品ee值随收率增大而减小，且降温速率越慢、晶种加入量越多，ee>99%的产品收率越高。

关键词: 青霉胺, 结晶, 热力学, 成核, 纯化

Abstract:

The solubility of DL- and D-penicillamine in ethanol-water mixed solvents with different mass ratios at 273.15—333.15 K was measured, and the appropriate crystallization solvent ratio was determined. The solubility curves of penicillamine at 273.15 K, 283.15 K, 293.15 K, 303.15 K, 313.15 K and 323.15 K were drawn. The width of the metastable zone of D- and DL-penicillamine and the solution with ee value of 87% was measured. The initial nucleation of saturated solutions with different ee values (saturation temperature of 313.15 K) under different initial subcooling, and the thermostatic crystallization process of saturated solutions with ee value of 87% under different initial subcooling and seed amount were studied. Finally, the crystallization resolution of raw materials with an ee value of 87%, different cooling rates and seed amounts were preliminarily investigated. The results show that, for the thermostatic crystallization process, as the crystallization progresses, the ee value of the product decreases, and the greater of initial subcooling, the more of seeds, the higher of the yield of the product with ee > 99%. For the cooling crystallization process, the ee value of the product decreases as the yield increases, and the slower of the cooling rate, the more of seeds, the higher of the yield of the product with ee> 99%.

Key words: penicillamine, crystallization, thermodynamics, nucleation, purification

中图分类号:

TQ 026.5

王东博, 张蕾蕾, 翟晶焕, 张丽娟, 刘锡建, 朱雪焱, 陆杰. 青霉胺结晶热力学及拆分工艺研究[J]. 化工学报, 2021, 72(4): 1885-1894.

WANG Dongbo, ZHANG Leilei, ZHAI Jinghuan, ZHANG Lijuan, LIU Xijian, ZHU Xueyan, LU Jie. Study on the crystallization thermodynamics and chiral resolution of penicillamine[J]. CIESC Journal, 2021, 72(4): 1885-1894.

图/表 13

图1 DL-和D-青霉胺在不同质量比乙醇-水混合溶剂中的溶解度

Fig.1 Solubility of DL- and D-penicillamine in ethanol-water mixed solvents with different mass ratios

图2 D-和DL-青霉胺残余固体的热分析谱图

Fig.2 DSC and TGA thermograms of the residual solids of D- and DL-penicillamine

图3 D-和DL-青霉胺原料与固液平衡后残余固体的X射线衍射谱图a—DL-残余固体；b—DL-原料；c—D-残余固体；d—D-原料

Fig.3 XRD patterns of the raw materials and the residual solids after solid-liquid equilibrium of D- and DL-penicillamine

图4 不同ee值青霉胺的溶解度a—323.15 K；b—313.15 K；c—303.15 K；d—293.15 K；e—283.15 K；f—273.15 K

Fig.4 The solubility of penicillamine with various ee values

图5 D-青霉胺、DL-青霉胺和ee=87%饱和溶液的介稳区宽度

Fig.5 The MSZW of D-penicillamine,DL-penicillamine and saturation solution with ee=87%

图6 过冷度对初始成核的影响

Fig.6 Effect of subcooling on initial nucleation

图7 固体ee值随结晶时间的变化

Fig.7 Change of the ee value of solids with crystallization time

图8 固体ee值随时间变化曲线

Fig.8 Curve of solid ee values over time

表1 青霉胺恒温结晶收率

Table 1 Yield of penicillamine of thermostatic crystallization

晶种量/%	产品收率
晶种量/%	ΔT=6 K	ΔT=10 K	ΔT=15 K
1	13.47%	19.67%	21.03%
2	14.27%	21.65%	22.31%
4	15.14%	23.86%	24.74%
8	16.21%	24.62%	25.35%

图9 结晶过程中固体和母液ee值变化

Fig.9 Change in ee value of the solid and mother liquor during crystallization process

图10 青霉胺恒温结晶过程Tc—结晶温度303.15 K；Tsat—饱和溶液温度313.15 K；Eut—二元共饱和点曲线；ee0—初始饱和溶液的ee值；trajectory—结晶过程曲线

Fig.10 The thermostatic crystallization process of penicillamine

图11 固体ee值在不同降温速率中随时间变化曲线

Fig.11 Curve of solid ee values over time at different cooling rates

表2 青霉胺降温结晶收率

Table 2 Yield of penicillamine of cooling crystallization

晶种量/%	产品收率
晶种量/%	0.05 K/min	0.1 K/min	0.2 K/min	0.4 K/min
1	13.04%	12.56%	10.31%	8.18%
2	20.23%	19.13%	17.54%	12.53%
4	24.91%	24.05%	21.43%	14.86%
8	25.97%	25.28%	22.89%	15.94%

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