Bis(methylphosphonic acid) derivatives of 1,4,8,11-tetraazacyclotetradecane (cyclam). Synthesis, crystal and molecular structures, and solution properties

Cyclam derivatives with methylphosphonic acid arms in position 1,8 and subs tituent R = H, Me, CH2Ph in positions 4 and 11 are synthesised by Mannich r eaction of an appropriate cyclam derivative, formaldehyde and phosphonic ac id/diethyl phosphite followed by removal of protecting benzyl groups from n itrogen atoms. Mono(methylphosphonic acid) derivative of cyclam can be obta ined by a similar route. Crystal structures of four phosphonic acid derivat ives show the same ring conformation and orientation pendants due to strong intramolecular hydrogen bonds between phosphonate oxygen atoms and protona ted nitrogen atoms adjacent over ethylene chains. The hydrogen bonds are st able 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 en hanced basicity of the nitrogen atoms non-bonded to methylene-phosphonic ac id moiety, is explained by the presence of the strong hydrogen bonds.