Variable‐Temperature Powder X‐ray Diffraction of Aromatic Carboxylic Acid and Carboxamide Cocrystals

The effect of temperature on the cocrystallization of benzoic acid (BA), pentafluorobenzoic acid (FBA), benzamide (BAm), and pentafluorobenzamide (FBAm) is examined in the solid state. BA and FBA formed a 1:1 complex 1 at ambient temperature by grinding with a mortar and pestle. Grinding FBA and BAm together resulted in partial conversion into the 1:1 adduct 2 at 28 °C and complete transformation into the product cocrystal at 78 °C. Further heating (80–100 °C) and then cooling to room temperature gave a different powder pattern from that of 2 . BAm and FBAm hardly reacted at ambient temperature, but they afforded the 1:1 cocrystal 3 by melt cocrystallization at 110–115 °C. Both BA+FBAm ( 4 ) and BA+BAm ( 5 ) reacted to give new crystalline phases upon heating, but the structures of these products could not be determined owing to a lack of diffraction‐quality single crystals. The stronger COOH and CONH₂ hydrogen‐bonding groups of FBA and FBAm yielded the equimolar cocrystal 6 at room temperature, and heating of these solids to 90–100 °C gave a new crystalline phase. The X‐ray crystal structures of 1 , 2 , 3 , and 6 are sustained by the acid–acid/amide–amide homosynthons or acid–amide heterosynthon, with additional stabilization from phenyl–perfluorophenyl stacking in 1 and 3 . The temperature required for complete transformation into the cocrystal was monitored by in situ variable‐temperature powder X‐ray diffraction (VT‐PXRD), and formation of the cocrystal was confirmed by matching the experimental peak profile with the simulated diffraction pattern. The reactivity of H‐bonding groups and the temperature for cocrystallization are in good agreement with the donor and acceptor strengths of the COOH and CONH₂ groups. It was necessary to determine the exact temperature range for quantitative cocrystallization in each case because excessive heating caused undesirable phase transitions.