Solvent-free mechanochemical synthesis and X-ray studies of Cu(II) and Ni(II) complexes of 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine (Trimethoprim) in a ball-mill

Solvent-free synthesis of [Cu(CH3COO)2(TMP)2](1) and [Ni(CH3COO)2(TMP)2](2) by ball milling of Cu(CH3COO)2.H2O and Ni(CH3COO)2.4H2O with Trimethoprim in the absence of solvent is described. Conventional synthesis of 1. CH3OH and 2. CH3OH was carried out by the reaction of metal acetate salt and Trimethoprim using the solution-based method (reflux in CH3OH for 2h) for comparison purposes. The mechanochemical products were characterized by comparison of melting points, conductivity values, spectral data, XRPD patterns with those of free ligand and solution based conventional synthesis products. X-ray diffraction patterns of the complex were similar to the simulated pattern of the complex obtained from single crystal structure suggesting the formation of identical compounds as obtained in solvent medium. The process presented here is operationally simple, environmentally benign and affords excellent yields without the need for solvents or external heating. Clearly, it can present a higher efficiency in terms of materials, energy and time compared to classical solution phase synthesis.