Collect. Czech. Chem. Commun. 2000, 65, 1289-1316

Bis(methylphosphonic Acid) Derivatives of 1,4,8,11-Tetraazacyclotetradecane (Cyclam). Synthesis, Crystal and Molecular Structures, and Solution Properties

Jan Kotek, Pavel Vojtíšek, Ivana Císařová, Petr Hermann*, Petr Jurečka, Jan Rohovec and Ivan Lukeš

Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 2030, 128 40 Prague 2, Czech Republic


Cyclam derivatives with methylphosphonic acid arms in position 1,8 and substituent R = H, Me, CH2Ph in positions 4 and 11 are synthesised by Mannich reaction of an appropriate cyclam derivative, formaldehyde and phosphonic acid/diethyl phosphite followed by removal of protecting benzyl groups from nitrogen atoms. Mono(methylphosphonic acid) derivative of cyclam can be obtained by a similar route. Crystal structures of four phosphonic acid derivatives show the same ring conformation and orientation pendants due to strong intramolecular hydrogen bonds between phosphonate oxygen atoms and protonated nitrogen atoms adjacent over ethylene chains. The hydrogen bonds are stable even in aqueous solution. Activation parameters for destabilisation of the conformation are estimated from temperature-dependent NMR measurement. The protonation constants determined confirm the expected high basicity of the compounds and its dependence on the nitrogen atom substituents. The enhanced basicity of the nitrogen atoms non-bonded to methylenephosphonic acid moiety, is explained by the presence of the strong hydrogen bonds.

Keywords: Azacrown compounds; Macrocycles; Cyclam; Tetrazacyclotetradecane; Phosphonic acids; Crystal structure; Conformation analysis; Basicity; Potentiometry; NMR spectroscopy; Protonation constants; Hydrogen bonds.

References: 67 live references.