Catalytic Activity\nof Triphenylphosphine for Electrophilic\nAromatic Bromination Using <i>N</i>‑Bromosuccinimide\nand Process Safety Evaluation

Electrophilic aromatic bromination using <i>N</i>-bromosuccinimide\n(NBS) is the most widely used reaction to synthesize highly functionalized\naromatic compounds. We encountered catalytic activity of triphenylphosphine\nfor aromatic bromination. This catalytic activity was successfully\napplied to a wide range of organic solvents and enabled the addition\nof NBS below the flash point of various organic solvents. Toward the\nindustrial implementation of this bromination, we evaluated the process\nsafety including the reaction heat and thermal decomposition. The\nanalysis revealed that the characteristic behavior of the reaction\nheat made it difficult to suppress the increase of the internal temperature.\nHowever, precise evaluation of the reaction heat suggested the sequential\naddition of NBS. This procedure suppressed the increase of the internal\ntemperature below 5 °C, which made the industrial implementation\nof this bromination feasible with process safety.