L-门冬氨酸钾结晶工艺研究

Crystallization for L-aspartic acid potassium salt

目的探索L-门冬氨酸钾盐的结晶方法,建立L-门冬氨酸钾盐的不同水合物的制备工艺。方法考察了不同的氢氧化钾水溶液的浓度和温度对结晶的影响,确定水中析晶的最佳条件;在此基础上进一步加入有机溶剂以提高收率;采用不同有机溶剂进行二水合物晶型转化为半水合物的研究。结果与结论氢氧化钾水溶液的质量浓度为750 g·L^(-1)、温度为10℃为L-门冬氨酸钾盐在水中结晶的最佳条件;产物中加入甲醇可提高收率,并得到二水合物;二水合物经过甲醇、无水乙醇、丙酮及异丙醇转晶都可制得半水合物,其中无水乙醇转晶收率较高,且毒性低;二水合物与半水合物的热重分析、差示扫描量热及X-射线粉末衍射图谱存在显著差异,二水合物为晶态物质,半水合物为非晶态物质。

This study aims to explore crystal products of L-aspartic acid potassium salt from solvents and set up a versatile preparation process to produce different hydrates of L-aspartic acid potassium salt. To this end,firstly we designed a two-factor orthogonal experiment to explore the effects of concentrations of potassium hydroxide aqueous solution and temperatures on crystallization,and identified 750 g·L-1 KOH aqueous solution（i. e.,weight of potassium hydroxide/volume of potassium hydroxide aqueous solution） and 10 ℃ as the best conditions for crystallization in water. We further added methanol to the product crystallized from water and recrystallize,and found out that this step produced higher yields of crystal products. The products were identified as dihydrates by Karl Fischer titration. In addition,we explored the potential of using four solvents（methanol,ethanol,acetone and isopropanol） for the conversion of dihydrate to other kinds of hydrates. Results have shown all these solvents were able to convert dihydrate to semihydrate while ethanol resulted in the highest yield and it was the least toxic. Lastly,we used thermogravimetry analysis（TGA）,differential scanning calorimetry（DSC） and X-ray powder diffraction（XRPD） to characterize dihydrate and semihydrate and observed that the former product was crystal while the latter was amorphous. The preparation process and conditions presented in this paper would be helpful for the large-scale production of dihydrate and semihydrate of L-aspartic acid potassium salt.