Clean synthesis of crystalline p-nitrobenzyl bromide from p-nitrotoluene with zero organic discharge

Abstract

2 : 1 : 3 NaBr-NaBrO₃-NaCl (obtainable as a low cost and eco-friendly reagent from an alkaline bromine intermediate) has been utilized previously in a number of bromination reactions. One such reaction is the conversion of p-nitrotoluene (PNT) to p-nitrobenzyl bromide (PNBBr) used widely for functional group protection. In the present work, selective cold (0–5 °C) crystallization of PNBBr from the reaction mixture containing ca. 2.5 M PNBBr along with 2.5–5.0 M PNT in ethylene dichloride (EDC) was found to be a winning move which led to gains in two fronts. It allowed the bromination reaction to be carried out cleanly and also enabled direct recycling of the mother liquor in the subsequent batch. Para NO₂-Ph-CHBr₂ impurity, which built up gradually in the reaction mixture over 8 batches, was converted into PNBBr/PNT through treatment of the mother liquor with NaBH₄, thereby helping to recycle the liquor perpetually and eliminate organic waste. EDC was the sole solvent in the entire process and its losses were minimal. The combined yield of isolated and recoverable PNBBr was 98.30% with respect to PNT consumed. The reagent utilization efficiency was 98.26%.