Guan, Mingxing, Tian, Yingtao, Zhao, Jibin, Gu, Wayne, Jiang, Xigui, Wang, Xufan, Zhang, Yongbo and Zhang, Xingmin (2021) Safe Scale-Up of a NBS-Involved Bromination Reaction: Thermal Safety Analysis Contributes to Process Optimization. Organic process research & development, 25 (6). pp. 1375-1382.

Abstract

A hazardous side reaction between N-bromosuccinimide (NBS) and 2-methyltetrahydrofuran (2-MeTHF) was identified during the thermal safety analysis towards a bromination process. The thermal behaviors of the side reaction was investigated by Calvet calorimeter C80 in a membrane mixing cell. A delay to initiate the reaction was observed, and it was owing to a preferred free-radical mechanism that the reaction could follow. The Advanced Kinetics and Technology Solutions (AKTS) software was used to study the thermo-kinetics of the side reaction, and its reaction progress under the proposed process temperature was predicted. The influence of NBS concentration on the side reaction was studied by differential scanning calorimeter (DSC). It was proved that the maximum reaction heat could be lowered by limiting the accumulation of NBS in the reaction mixture. Besides, the heat flow of the process desired reaction was simulated by reaction calorimeter (RC1), indicating the bromination could be controlled under a semi-batch mode with appropriate feeding program of NBS. On the basis of the investigation, two batches bromination process with 106 kg starting material were safely scaled up in pilot plant with expected yield.

Item Type:	Article
Date Deposited:	13 Jul 2021 00:45
Last Modified:	13 Jul 2021 00:45
URI:	https://oak.novartis.com/id/eprint/44449