Design of a series of cocrystals featuring isoniazid modified with diacetone alcohol

Abstract

Eight cocrystals containing an isoniazid derivative derivatized with diacetone alcohol [N′-[(2E)-4-hydroxy-4-methylpentan-2-ylidene]pyridine-4-carbohydrazide, iz4h4m2p] were synthesized and characterized. All coformers used in this work feature at least one carboxylic acid functional group. These coformers include: succinic acid, 3,5-dinitrobenzoic acid, 4-nitrobenzoic acid, 2-chloro-4-nitrobenzoic acid, 2,5-dihydroxybenzoic acid, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid and cinammic acid. Crystal structures were obtained using single crystal X-ray diffraction, which shows that cocrystals containing iz4h4m2p feature a similar chain hydrogen bond between molecules of iz4h4m2p in addition to the expected carboxylic acid...pyridine hydrogen-bond interaction. Differences between the structures arise when additional hydroxyl group(s) are present, such as the case featuring the hydroxybenzoic acids. These structures are compared to their isoniazid counterparts presented previously in the literature. All cocrystals were also characterized with differential scanning calorimetry and Fourier transform infrared spectroscopy.