Co-Crystals of Caffeine and Hydroxy-2-naphthoic Acids:  Unusual Formation of the Carboxylic Acid Dimer in the Presence of a Heterosynthon

A group of caffeine-containing co-crystals of hydroxy-2-naphthoic acids were synthesized and analyzed via single-crystal X-ray diffraction and IR analysis. The imidazole−carboxylic acid synthon was observed in co-crystals involving 1-hydroxy-2-naphthoic and 3-hydroxy-2-naphthoic acid. In the case of 6-hydroxy-2-naphthoic acid, the co-crystal exhibits a hydrogen-bonded carboxylic acid dimer in the presence of a hydroxyl−caffeine heterosynthon. Keywords: Pharmaceutical co-crystals; co-crystal screening; hydrogen bond; caffeine; naphthoic acid; supramolecular synthon; crystal engineering; 1-hydroxy-2-naphthoic acid; 3-hydroxy-2-naphthoic acid; 6-hydroxy-2-naphthoic acid