The design of a series of cocrystals featuring dicarboxylic acid with a modified isoniazid derivative

Abstract

A series of cocrystals featuring an isoniazid derivative was synthesized and characterized. Isoniazid was derivatised using acetone to make N′-(propan-2-ylidene)pyridine-4-carbohydrazide (izact). An attempt to form seven new cocrystals was made, which involved cocrystalizing izact an aliphatic dicarboxylic acid of varying chain lengths ranging from malonic acid (C3) to sebacic acid (C10), excluding succinic acid (C4) since this cocrystal was reported before. Out of these, only five cocrystals were successfully synthesized; since an attempt to form a cocrystal with malonic acid (C3) and glutaric acid (C5) failed, leaving the successful cocrystals to contain dicarboxylic acids ranging from adipic acid (C6) to sebacic acid (C10). These izact–dicarboxylic acid cocrystals were then compared to their isoniazid counterparts, as well as that with the previously reported izact–C4 cocrystal. This comparison showed that the cocrystals of izact with C4, C6, C8 were isostructural, while the other cocrystals reported here showed unique aspects that differentiated them from their counterparts. Single-crystal X-ray diffraction (SC-XRD) was used to determine the crystal structures, while powder X-ray diffraction (PXRD) was used to determine the bulk phase purity. Differential scanning calorimetry was used to determine any additional phases but only melting was observed.