Abstract:
Two cocrystal polymorphs of ethenzamide (ETZ) and ethylmalonic acid (EMA) were synthesized by solvent evaporation. Crystal structure analysis revealed that the main amide - carboxyl heterosynthon in ETZ-EMA cocrystal Form I and Form II are the same, but the crystal structure of these two polymorphs are different. Terahertz (THz) and Raman vibrational spectroscopy were used to characterize ETZ, EMA, ETZ-EMA cocrystal polymorph Form I and Form II respectively. The experimental results showed that ETZ, EMA, ETZ-EMA cocrystal Form I and ETZ-EMA cocrystal Form II exhibited completely different characteristic peaks. Both THz and Raman vibrational spectroscopy can be used to distinguish ETZ-EMA cocrystal Form I from Form II. Furthermore, the investigation of phase transition induced by temperature and solid-state grinding was also performed. In the temperature phase transition experiments, when the powder sample was heated to a temperature range of 80-82 °C, the metastable ETZ-EMA cocrystal Form I transformed into the more stable ETZ-EMA cocrystal Form II. Solid-state grinding analysis revealed that the results of the ETZ-EMA cocrystal polymorph synthesis in grinding experiments depended on the polarity of the solvents used. Grinding without solvent or with high polarity solvents tended to result in the stable ETZ-EMA cocrystal Form II. Moreover, the metastable ETZ-EMA cocrystal Form I would transform into Form II after further grinding process. These results demonstrate that THz and Raman vibrational spectroscopy have high sensitivity and accuracy in the detection of both cocrystal synthesis and cocrystal polymorph phase transitions.
摘要:
通过溶剂蒸发合成了两种乙苯甲酰胺(ETZ)和乙基丙二酸(EMA)的共晶多晶型物。晶体结构分析表明,ETZ-EMA共晶I型和II型中的主要酰胺-羧基杂合子是相同的,但是这两种多晶型物的晶体结构不同。使用太赫兹(THz)和拉曼振动光谱来表征ETZ,EMA,ETZ-EMA共晶多晶型物形式I和形式II分别。实验结果表明,ETZ,EMA,ETZ-EMA共晶形式I和ETZ-EMA共晶形式II表现出完全不同的特征峰。THz和拉曼振动光谱法均可用于区分ETZ-EMA共晶形式I与形式II。此外,还进行了由温度和固态研磨引起的相变的研究。在温度相变实验中,当粉末样品被加热到80-82°C的温度范围时,亚稳态ETZ-EMA共晶形式I转变为更稳定的ETZ-EMA共晶形式II。固态研磨分析表明,在研磨实验中ETZ-EMA共晶多晶型物的合成结果取决于所用溶剂的极性。没有溶剂或用高极性溶剂研磨倾向于产生稳定的ETZ-EMA共晶形式II。此外,在进一步的研磨过程之后,亚稳态ETZ-EMA共晶形式I将转变为形式II。这些结果表明,THz和拉曼振动光谱在检测共晶合成和共晶多晶型相变方面具有很高的灵敏度和准确性。