The chemistry of nitrogen coordinated tertiary carboxamides: a spectroscopic study on bis(picolyl)amidecopper(ii) complexes

Abstract

Metal coordination of the electrically neutral nitrogen atom of a tertiary carboxamide reduces the barrier to C-N-bond rotation and activates the amide towards methanolysis. X-Ray crystallographic studies indicate that this reactivity is correlated to a lifting of the amide resonance structure and concurrent pyramidalization at nitrogen. However, mechanistic data in solution have not been obtained. It became evident that structural mobility is characteristic of the complexes and the crystallographic data do not fully account for relevant reactive species. In this report we summarize IR, UV-vis, and EPR spectra of amide nitrogen coordinated bis(picolyl)amide complexes with copper(II) triflate and copper(II) chloride. A comparison between spectra sampled in the aprotic solvents dichloromethane and acetonitrile, as well as under methanolysis conditions reveals the nature of several species formed in solution. The key reactions are (I) ligand exchange involving either CH3CN or CH3OH, or, in IR experiments, bromide ions from KBr, (II) coordination-dissociation equilibria involving the urethane protecting groups of amino acid substituted ligands Boc-Xaa-bpa (Boc = tert-butoxycarbonyl, Xaa = glycine, alanine, and leucine, respectively, bpa = bis(picolyl)amine), (III) dissociation of a chloro ligand from LCuCl2 complexes and formation of square-pyramidal complex cations [LCuCl]+, and finally (IV) complete dissociation of the polydentate tertiary amide ligand to produce free copper ions in solution. Taken together, the results provide a fairly detailed qualitative picture of the processes which accompany the amide bond methanolysis.

Chelating Carboxylic Acid Amides as Robust Relay Protecting Groups of Carboxylic Acids and their Cleavage under Mild Conditions

“…All the reactions occurred in good to very high yields, thus demonstrating the potential of this relay protecting group principle. It is also noteworthy that the formation of the carboxylic acids required only 20 equivalents of Ba(OH) 2 ·8 H 2 O instead of the 400 equivalents reported in references [5][6][7]. The results revealed at the same time that the system was compatible with aromatic (Table 1, a-c), aliphatic (d, e), and amino acids (f, g).…”

“…As in the linker systems mentioned above, activation for methanolysis would proceed by an unusual complexation involving the nitrogen atom of the amide bond. [5] Alternatively, methanolysis mediated by the complexation could be performed in the presence of Ba(OH) 2 ·8 H 2 O, [6][7][8] which would then yield carboxylic acid 1 directly after acidic workup. Activation by complexation was hitherto only sparsely exploited in the realm of protecting groups, despite the fact that it would add a further degree of orthogonality to commonly used deprotection methods.…”

A New Robust and Versatile Tetradentate Linker for Amides To be Cleaved under Mild Conditions by Unusual Complexation of the Amide Nitrogen to Cu++

“…[2] Hence, we surmised that in the Cu II complexes of 13 and 14 the copper is forced into a square coordination and not flexible enough to adopt the required distorted octahedral shape. As a consequence, the more flexible linear tetradentate ligand 22 was synthesized (Scheme 4), which after cleavage of the Boc group should allow attachment of carboxylic acids through amide bonds.…”

“…[2] An additional nitrogen atom for complexation should lead to a more stable complex and as a consequence to a more pronounced weakening of the amide bond allowing, even milder conditions, amide bond cleavage.…”

Towards the Preparation of Novel Re/99mTc Tricarbonyl-Containing Peptide Nucleic Acid Bioconjugates

“…Such compounds were shown to be excellent ligands for metal ions, especially for Cu(II), Cd(II) and Zn(II). [45][46][47][48][49][50][51][52][53][54][55][56][57] Noteworthy, Alsfasser, Vahrenkamp et al have inserted such Dpam ligands to the side-chain of amino acids in order to introduce metal complexes in peptide frameworks for medicinal and biological applications. 45,47,48,52,53,57 However, to the best of our knowledge, no Re or Tc tricarbonyl complexes coordinated to such ligands have been reported to date.…”