Amide cleavage reactivity in synthetic metal complexes: Influence of ligand structure and divalent metal ion

In this work, we have investigated the effect of changing the chelate ligand structure on the amide cleavage reactivity of zinc complexes. Three new amide-appended ligands were prepared and characterized. Zinc complexes of the ligands, [(dpppa)Zn](X)2, [(bdppa)Zn](X)2, [(epppa)Zn](X) 2, where X= ClO4- or CF3SO 3-; dpppa = ((N,N-diethylamino)ethyl)- N-((6-pivaloylamido-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; bdppa =N,N-bis(N,N-diethylamino)ethyl- N-((6-pivaloylamido-2-pyridyl)methyl)amine; epppa = N-((2-ethylthio)ethyl)- N-((6-pivaloylamido-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine, were prepared and characterized using multiple physical methods. When treated with base in methanol, [(dpppa)Zn](X)2 and [(epppa)Zn](X) 2 undergo amide methanolysis. Prior to amide cleavage, all of the zinc complexes form a deprotonated amide intermediate. When treated with methanol, the intermediate of [(bdppa)Zn](X)2 did not undergo amide cleavage. These intermediates have been isolated and characterized using 1H and 13C NMR, IR and elemental analysis. Kinetic studies of the amide methanolysis of [(dpppa)Zn](X)2 and [(epppa)Zn](X) 2 have been performed; from an Eyring plot, thermodynamic parameters have been obtained. On the basis of the above results an explanation for the difference in reactivity of these zinc complexes is presented. The amide cleavage reaction of [(bmppa)Zn](ClO4)2 was more complicated. When treated with base, a mixture of the intermediate along with free chelate ligand was observed in the reaction mixture.; We have also examined the effect of a change in the metal ion on the amide methanolysis reactivity in synthetic metal complexes. In this regard, [(bmppa)Ni](ClO4)2, [Co(bmppa)](ClO4) 2, and [Fe(bmppa)](ClO4)2 (bmppa = N,N -bis(2-methylthio)ethyl-N-((6-pivaloylamido-2-pyridyl)methyl)amine) complexes were synthesized and characterized using multiple physical methods. [Co(bmppa)](ClO4)2, and [Fe(bmppa)](ClO4) 2 were also characterized by X-ray crystallography.; When treated with hydroxide, [(bmppa)Ni](ClO4)2, and [Co(bmppa)](ClO4)2 form a deprotonated intermediate, while [Fe(bmppa)](ClO4)2 undergoes reaction to give free chelate ligand and a precipitate of an unidentified iron species. When the deprotonated amide complexes of nickel and cobalt were treated with methanol at 50°C for 5 days, the deprotonated intermediate of cobalt undergoes amide methanolysis. However, the reaction was very slow and ∼50% yield of amide cleavage products was obtained. The deprotonated intermediate of nickel did not undergo amide cleavage under similar conditions. A rationale for the difference in the reactivity of these metal complexes as compared to a Zn(II) analog was proposed on the basis of structural differences in the "parent" protonated complexes.