Abstract
Ferrocene derivatives, namely, 4-ferrocenyl-4-oxo-butanoic acid (F1), 4-ferrocenylbutanoic acid (F2), ferrocenylmethyleneamine (F5) and ferrocenylethyleneamine (F6), were synthesized. The aminobisphosphonic acids, Alendronate ((4-amino-1-hydroxy-1-phosphobutyl) phosphonate), B1, (5-amino-1-hydroxy-1-phosphopentyl) phosphonate, B2, and neridronate ((6-amino-1-hydroxy-1-phosphohexyl) phosphonate), B3, tetraethylvinylidenephosphonate, B4, and tetraethyl-3-aminopropane-1-1-bisphosphonate, B5 were also synthesized. Various ferrocene and bisphosphonates derivates were then hybridized via amine and amide bond formation to get a series of ferrocene-bisphosphonate hybrid compounds (H1-H8) in 55-83% yield. H1-H3 were synthesized by reductive amination of ferrocene carboxaldehyde, F4 with aminobisphosphonic acids, B1, B2 and B3 respectively. Hybrids H4-H6, were obtained by direct coupling of ferrocenecarboxylic acid, F3, 4-ferrocenylbutanoic acid, F2 and 4-ferrocenyl-4-oxo-butanoic acid, F1, respectively with tetraethyl-3-aminopropane-1-1-bisphosphonate, B5, using a 50 % solution of propylphosphonic anhydride (T3P) in ethyl acetate as a coupling agent. H7a was prepared from ferrocenylmethyleneamine (F5) and tetraethylvinylidenebisphosphonate (B4) in a Michael addition type reaction, while H8 was obtained by reductive amination of ferrocene carboxaldehyde, F4, with tetraethyl-3-aminopropane-1-1-bisphosphonate, B5. All synthesized compounds were characterised by a combination of 1H, 31P{1H} and 13C{1H} nuclear magnetic resonance (NMR) spectroscopy, fourier transform-infrared (FT-IR) and high-resolution mass spectrometry (HRMS)...
D.Phil. (Chemistry)