N‐H⋅⋅⋅O, O‐H⋅⋅⋅O hydrogen bonded supramolecular formation in the cocrystal of salicylic acid with N‐containing bases

Abstract

Cocrystals of salicylic acid (derived from reaction between aspirin and coformers) with 4,4′dipyridyl, nicotinamide, isonicotinamide, N,N′‐diacetylpiperazine and piperazine have been examined with intent to improve physicochemical properties of antipyretic agent. All of the resulting cocrystals, salicylic acid/4,4′dipyridyl (2:1), salicylic acid/nicotinamide (1:1), salicylic acid/isonicotinamide (1:1), salicylic acid/piperazine (1:0.5) and salicylic acid/ N,N′‐diacetylpiperazine (2:1) (derived from reaction between aspirin and piperazine) are obtained solution cooling/evaporation experiments. The structural analysis has shown that the well‐known COOH⋅⋅⋅N heterosynthon was considered the key element in the cocrystals design strategy. The carboxylic acid⋅⋅⋅pyridine hydrogen bond is an often used supramolecular synthon. The results from X‐ray Powder Diffraction, DSC, Raman and single‐crystal X‐ray analysis revealed the formation of cocrystal of salicylic acid with several coformers.