Design and Optimization of the Single-Stage Continuous Mixed Suspension–Mixed Product Removal Crystallization of 2‑Chloro‑N‑(4-methylphenyl)propenamide

A continuously operated single-stage mixed suspension–mixed product removal (MSMPR) crystallizer was developed for the continuous cooling crystallization of 2-chloro-N-(4-methylphenyl)­propanamide (CNMP) in toluene from 25 to 0 °C. The conversion of the previous batch to a continuous process was key to developing a methodology linking the synthesis and purification unit operations of CNMP and gave further insight in the development of continuous process trains for active pharmaceutical ingredient materials. By monitoring how parameters such as cooling and agitation rates influence particle size and the yield, two batch start-up strategies were compared. The second part of the study focused on developing and optimizing the continuous cooling crystallization of CNMP in the MSMPR crystallizer in relation to the yield by determining the effects of varying the residence time and the agitation rates. During the MSMPR operation, the plot of the focused beam reflectance measurement total counts versus time oscillates and reaches an unusual state of control. Despite the oscillations, the dissolved concentration was constant. The yield and production rate from the system were constant after two residence times, as supported by FTIR data. The overall productivity was higher at shorter residence times (τ), and a productivity of 69.51 g/h for τ = 20 min was achieved for the isolation of CNMP.