Management of the Heat of Reaction under Continuous Flow Conditions Using In-Line Monitoring Technologies

• Masahiro Hosoya
• Shogo Nishijima
• Noriyuki Kurose

• API R&D Laboratory, CMC R&D Division, Shionogi and Co., Ltd., 1-3, Kuise Terajima 2-chome, Amagasaki, Hyogo 660-0813, Japan

This work presents a guideline for managing process safety under continuous flow conditions. In our previous work, we developed a Grignard reaction for use under such conditions. This reaction was completed in seconds and entailed a large amount of heat generation. To manage the heat of reaction, we quantitatively analyzed the reaction rate using ReactIR with a flow cell. The difference between quantitative values from HPLC and ReactIR was less than 1%, and the reaction rate was 94% in 0.4 second. Based on the reaction rate and the heat of reaction, we simulated the distribution of the internal temperature along the tube length and found the maximum difference from the measured internal temperatures to be 5°C. This accuracy was suitable for evaluating and managing the heat of reaction. Our methodology can facilitate the discussion of process safety under continuous flow conditions.

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