Conformational analysis of the salts of N-[(2,3-dimethylphenoxy)alkyl]aminoalkanol derivatives

Four new crystal structures of the salts of N-[(2,3-dimethylphenoxy)alkyl]aminoalkanol derivatives with anticonvulsant activity are reported. Bis{D,L-trans-N-[(2,3-dimethylphenoxy)ethyl]-1-hydroxycyclohexan-2-aminium} succinate, 2C₁₆H₂₆NO₂⁺·C₄H₄O₄^2-, 1, and its polymorph 1p, crystallize in the monoclinic space group P2₁/n, 1 with two cations and one anion, and 1p with four cations and two anions in the asymmetric unit. The other two salts, D,L-trans-N-[(2,3-dimethylphenoxy)ethyl]-1-hydroxycyclohexan-2-aminium 6-carboxypyridine-2-carboxylate, C₁₆H₂₅NO₂⁺·C₇H₄O₄^-, 2, and N-[(2,3-dimethylphenoxy)propyl]-3-hydroxypiperidinium pyridine-2-carboxylate, C₁₆H₂₆NO₂⁺·C₆H₄O₂^-, 3, crystallize in the monoclinic space group P2₁/c, with one cation and one anion in each asymmetric unit. The geometry of the created polymorphs indicates the main differences in the conformation of the linker between the two rings. The arrangement of the ether O atom and the N atom shows an unusual antiperiplanar conformation for the cations of 1p. The crystal packing of all four salts is dominated by charge-assisted hydrogen bonding between the protonated N atom and the carboxylate group of the corresponding acid. Structural studies have been enriched by quantum chemical calculations.