Synthesis of N-methyl alkylaminomethane-1,1-diphosphonic acids and evaluation of their complex-formation abilities towards copper(II)

Abstract

A series of N-methyl alkylaminomethane-1,1-diphosphonic acids (3a–g) with a common tertiary nitrogen atom (CH3–N–R) bearing linear or branched alkyl, cycloheptyl or phenylalkyl R substituents was synthesized in the reaction of diethylphosphonate with triethyl orthoformate and secondary amine followed by hydrolysis, and by the Eschweiler–Clarke methylation of the alkylaminomethane-1,1-diphosphonic acids with formic acid and formaldehyde. Complex-formation abilities of 3a–g towards copper(II) in solution were studied by means of pH-potentiometry, ESI-MS spectrometry, UV–Vis and EPR methods.Evaluation of stability constants for the Cu(II) complexes of 3a–g has revealed their dependence on a combination of steric and electronic effects imposed by R substituents. It has been demonstrated that compounds with linear or branched alkyl on the N atom (3a, 3d, 3e) form the most stable complexes with Cu(II), the least stable are complexes of 3f, which can be attributed to the steric effect imposed by cycloheptyl ring attached directly to the N atom. In addition to the main [Cu(HL)2] complexes, with well-known {O, O} chelating binding mode, [Cu(HL)L] and [CuL2] species with the {O, N} donor set, protonated dinuclear [Cu2HxL3] (x=4, 5, 6) species have been detected in all studied systems. The nitrogen coordination in the [Cu(HL)L] and [CuL2] complex has been confirmed by Vis and EPR spectra.