Safe Scale-Up of an N‑Bromosuccinimide Involved Bromination Reaction

A hazardous side reaction between N-bromosuccinimide (NBS) and 2-methyltetrahydrofuran (2-MeTHF) was identified during the thermal safety analysis toward a bromination process. A delay reaction owing to a preferred free-radical initiation was observed. The progress of the side reaction and influence of NBS concentration on the reaction heat were studied by means of different calorimeters. The heat flow of the desired reaction was measured by the reaction calorimeter (RC1), indicating the bromination could be controlled under a semibatch mode with appropriate feeding program of NBS. On the basis of these investigations, two consecutive brominating processes with 106 kg starting material were safely scaled up in the pilot plant with expected yields.