Transforming Reactive Crystallization from Batch to Continuous: A Case Study of 1-Phenyl-3-methyl-5-pyrazolone Synthesis

Abstract

Crystallization plays a critical role in chemical manufacturing, and the production efficiency of many crystallization processes has been significantly improved through the transition from batch to continuous operation. However, due to the more stringent process requirements of reactive crystallization compared to other crystallization methods, there are almost no precedents for successfully implementing continuous reactive crystallization. This study used the 1-phenyl-3-methyl-5-pyrazolone (edaravone) reactive crystallization process as a case to explore detailed strategies for upgrading from batch to continuous operation and to evaluate the performance of the continuous process. The results demonstrate the successful implementation of continuous reactive crystallization for edaravone. Experimental data show that the crystallization efficiency of the continuous process is 916.7% higher than that of the batch process in reactors of the same volume. Compared with industrial-scale batch reactors, the continuous system can achieve an approximately 2308.2% improvement in crystallization efficiency. Additionally, the continuous process produces crystals with a higher uniformity, indicating superior product quality. This study provides actionable insights into continuous reactive crystallization, offering valuable guidance for the optimization and industrialization of the continuous reactive crystallization process.