Influence of protonation on the geometry of 2‐{[(2,6‐dimethylphenoxy)ethyl]amino}‐1‐phenylethan‐1‐ol: crystal structures of the free base and of its chloride and 3‐hydroxybenzoate salt forms

• Published in: Acta crystallographica. Section C, Crystal structure communications Crystal structure communications, 2022-01, Vol.78 (1), p.14-22
• Main Authors: Nitek, Wojciech, Kania, Agnieszka, Marona, Henryk, Waszkielewicz, Anna M., Żesławska, Ewa
• Format: Article
• Language: English
• Subjects: 3‐hydroxybenzoic acid; aminoalkanol; Anions; anticonvulsant activity; Anticonvulsants; Aromatic compounds; aroxyalkyl derivative; Cations; Chains; Chlorides; Crystal structure; Crystallography, X-Ray; Crystals; Hydrogen; Hydrogen Bonding; Hydrogen bonds; Hydroxybenzoates; Molecular Structure; Protonation; Salts
• ISSN: 2053-2296; 0108-2701; 2053-2296; 1600-5759
• DOI: 10.1107/S2053229621012614

The aroxyalkylaminoalcohol derivatives are a group of compounds known for their pharmacological action. The crystal structures of four new xylenoxyaminoalcohol derivatives having anticonvulsant activity are reported, namely, 2‐{[2‐(2,6‐dimethylphenoxy)ethyl]amino}‐1‐phenylethan‐1‐ol, C18H23NO2, 1, the salt N‐[2‐(2,6‐dimethylphenoxy)ethyl]‐1‐hydroxy‐1‐phenylethan‐2‐aminium 3‐hydroxybenzoate, C18H24NO2+·C7H5O3−, 2, and two polymorphs of the salt (R)‐N‐[2‐(2,6‐dimethylphenoxy)ethyl]‐1‐hydroxy‐1‐phenylethan‐2‐aminium chloride, C18H24NO2+·Cl−, 3 and 3p. Both polymorphs crystallize in the space group P21212 and each has two cations and two anions in the asymmetric unit (Z′ = 2). The molecules in the polymorphs show differences in their molecular conformations and intermolecular interactions. The crystal packing of neutral 1 is dominated by intermolecular O—H…N hydrogen bonds, resulting in the formation of one‐dimensional chains. In the crystal structures of the salt forms (2, 3 and 3p), each protonated N atom is engaged in a charge‐assisted hydrogen bond with the corresponding anion. The protonation of the N atom also influences the conformation of the molecular linker between the two aromatic rings and changes the orientation of the rings. The crystal packing of the salt forms is dominated by intermolecular O—H…O hydrogen bonds, resulting in the creation of chains and rings. Structural studies have been enriched by the calculation of Hirshfeld surfaces and the corresponding fingerprint plots. The crystal structures of four new xylenoxyaminoalcohol derivatives having anticonvulsant activity, three of which are salts, are reported. The protonation of the N atom influences the conformation of the molecular linker between the two aromatic rings and changes the orientation of the rings. Structural studies have been enriched by the calculation of Hirshfeld surfaces and the corresponding fingerprint plots.