Control of the agglomeration of crystals in the reactive crystallization of 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole

Abstract

5-(Difluoromethoxy)-2-mercapto-1H-benzimidazole (DMB) was precipitated by adding acetic acid to the DMB sodium salt solution. The spherical agglomeration of DMB during the reactive crystallization in a batch crystallizer was monitored by real-time Particle Video Microscope (PVM). We found that the low feeding rate of acetic acid, high crystallization temperature, low agitation rate or adding seed crystal can facilitate the formation of spherical agglomerates. By using a simple model, the mean crystal agglomerate size of DMB thus predicted is generally in agreement with the experimental data. In addition, the crystallization process of DMB was optimized by a new control strategy of supersaturation to avoid disadvantages brought by agglomeration.

Key words： 5-(difluoromethoxy)-2-mercapto-1H-benzimidazole (DMB); reactive crystallization; agglomeration; feeding rate; crystallization temperature; agitation rate

Acknowledgments

The authors are very grateful to Shenyang Hongfei Medical Chemical Plant of China for supplying DMB and to the State Research Center of Industrialization for Crystallization Technology (in China) and the National Natural Science Foundation of China (Grant No. 20836005) for the financial assistance.

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