Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation

Wang Chunxiao; Wang Shuai; Zhang Hongsen; Li Chao; Qiao Renzhong

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Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation

Updated：2026-03-13

- Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation
- Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation
- 中国化学工程学报（英文） 2026年89卷第1期页码：83-92
- Affiliations：
  
  State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China
- Author bio：
  
  Corresponding authors. E-mail addresses: lichao@mail.buct.edu.cn(C. Li)
  qiaorz@mail.buct.edu.cn(R. Qiao).
- Funds：
  
  the National Natural Science Foundation of China(22177011;21977012;21572018);the National High-Level Hospital Clinical Research Funding(2023-NHLHCRF-YXHZ-ZRMS-02);the Joint Project of BRCBC (Biomedical Translational Engineering Research Center of BUCT-CJFH)(XK2020-06)
- DOI：
  中图分类号：
- 收稿：2025-06-25，
  
  修回：2025-08-11，
  
  录用：2025-08-12，
  
  网络首发：2025-10-24，
  
  纸质出版：2026-01
- Accepted：
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Wang Chunxiao, Wang Shuai, Zhang Hongsen, 等. Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation[J]. 中国化学工程学报（英文）, 2026,89(1):83-92.

Wang Chunxiao, Wang Shuai, Zhang Hongsen, et al. Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation[J]. Chinese Journal of Chemical Engineering, 2026, 89(1): 83-92.
Wang Chunxiao, Wang Shuai, Zhang Hongsen, 等. Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation[J]. 中国化学工程学报（英文）, 2026,89(1):83-92. DOI：

Wang Chunxiao, Wang Shuai, Zhang Hongsen, et al. Cocrystal engineering for efficient separation of 4-bromo-3-methylphenol: Design of experiments, characterization, crystal structure and calculation[J]. Chinese Journal of Chemical Engineering, 2026, 89(1): 83-92. DOI：

摘要

Abstract

4-Bromo-3-methylphenol (BMP) is an important chemical intermediate with wide applications in the fields of medicine and pesticides. The synthesis of BMP from

-cresol

via

bromination is easy to c

arry out on an industrial scale. However

due to the formation of regioisomeric impurities during bromination and the low melting point of BMP

the separation process is prone to the formation of oily substances

resulting in low yield and purity. In this work

a new cocrystallization engineering approach was proposed to separate and purify BMP. Through design of experiments

the cocrystallization process of BMP and triethylenediamine (DABCO) was optimized using a minimum-run resolution IV screening design combined with response surface methodology. In addition

the obtained 2BMP-DABCO powder was characterized by thermal analysis

powder X-ray diffraction

infrared spectroscopy

and scanning electron microscopy. Single crystals of 2BMP-DABCO were grown from acetone by slow evaporation

and detailed structural information was obtained through single-crystal X-ray diffraction. The self-assembly mechanism was further clarified by density functional theory calculations. This study provides a simple

robust

and scalable method for the production of BMP and offers a reference for the separation and purification of phenolic substances.

关键词

Keywords

references

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