Purification of nitrophenols using complex-assisted crystallization

Solution-phase chemical complexation can be used to enhance the purity of crystallized products. Using the separation of nitrophenol isomers as a model, we experimentally demonstrated that complex-assisted crystallization can efficiently remove structural isomers as impurities without affecting product crystal form or decreasing yield. Experiments showed that lattice-impurity incorporation of 3-nitrophenol into 4-nitrophenol can be prevented in an aqueous system using 3-aminobenzoic acid as a complexing agent. Purity enhancements of more than 80% (mass) with respect to non-complexed controls were observed with no yield reduction. The formation of complexes in solution was verified experimentally by measuring the change in rejection coefficient of the impurity through a nanofiltration membrane in the presence of the complexing agent. These results serve to further the known applicability of complex-assisted crystallization as a technique for enhancing traditional crystallization processes, providing the first example of a system without a carboxylic acid-containing impurity and the first separation of structural isomers. Complex assisted crystallization was used to purify structural isomers, increasing purity by 80% with respect to controls without reducing yield.