Intermolecular interactions in hydrates of 4-methylpiperidine and 4-chloropiperidine - a structural and computational study

The structures and interactions in four new hydrates of substituted piperidines have been studied using X-ray crystallography and quantum chemistry. The piperidine ring substitution leads to a significant reduction in the number of hydrates compared with the parent amine, with 4-methylpiperidine yielding a hemihydrate and a trihydrate; 4-chloropiperidine a monohydrate and a trihydrate, (where the architecture is similar to 4-methylpiperidine trihydrate). Despite many attempts, it did not prove possible to crystallize hydrates with higher molar amine : water ratios. Therefore, trihydrates are probably the most hydrated crystals to be obtained at ambient pressure for both amines. Both trihydrates create identical water layers of the L4(6)5(7)6(8) type and the main structural difference is the arrangement of hydrogen bonds between water layers and amines. Despite this, both trihydrates have the same melting temperature (263 K) and as supported by lattice energy calculations. Chlorine.chlorine contacts have no significant impact on the stabilization of the 4-chloropiperidine monohydrate or the 4-chloropiperidine trihydrate. Periodic DFT-D3 calculations show that the energies of the water layers are identical in both cases, and the summed hydrogen bond energies (although arranged differently) are similar. Moreover, in the case of trihydrates, which have a 2-D topology of water...water interactions, it is possible to perform DFT calculations for separate layers and to determine the contribution of those interaction energies to the cohesive energy of the whole crystals.

Automated summary

The structures and interactions of four new hydrates of substituted piperidines were investigated using X-ray crystallography and quantum chemistry. The study found that the number of hydrates significantly decreased with piperidine ring substitution. Despite structural differences, hydrates with different substitutions had the same melting temperature, and chlorine...chlorine interactions had no significant impact on the stability of the hydrates.