Intriguing relationships and associations in the crystal structures of a family of substituted aspirin molecules

A number of ring-substituted aspirin molecules have been synthesised and their crystal structures determined. All contain the strongly H-bonded carboxylate dimer found in the two forms of aspirin itself. Detailed analysis of the further packing of this dimer reveals that the 5-chloro, 5-bromo and 5-iodo derivatives form an isostructural group, as do the 5-fluoro, 5-methyl and 5-nitro derivatives. The 3-methyl and 4-methyl structures have close 3D similarity and may be classified as pseudoisostructural. The structures of the first two groups have a common 1D stack of dimers which contributes to two different 2D layers. One of the 2D layers is found in the fluoro, nitro and 5-methyl isostructures and also in the 3-methyl and 4-methyl derivatives. The second layer motif is found in the chloro, bromo and iodo groups and is also present in the fluoro, nitro and 5-methyl structures. The 6-methyl structure shares a 1D motif with the chloro, bromo and iodo groups. The packing variations are linked to different types of intermolecular interactions. In the 5-Cl, Br, and I groups, we find short Hal⋯O contacts to the carboxylate carbonyl; in the 5-F, 5-NO2 and 5-Me derivatives we find the acyl⋯acyl dimer interaction, present also in aspirin form I. In addition, the 5-F structure contains F⋯O short contacts to a carboxylate hydroxyl oxygen and in the 5-NO2 we find N–O⋯H–C contacts to an acyl methyl group.