Three-center intramolecular hydrogen bonding in oxamide derivatives. NMR and X-ray diffraction study

Abstract

This contribution describes the synthesis and structural investigation of the symmetric and nonsymmetric oxamides N,N Ј-bis(2-hydroxyphenyl)oxamide 1, N,N Ј-bis(5-tert-butyl-2-hydroxyphenyl)oxamide 2, N,N Ј-bis(3,5-dimethyl-2-hydroxyphenyl)oxamide 3, N,N Ј-bis(2-hydroxybenzyl)oxamide 4, N,N Ј-diphenethyloxamide 5, N-(2-hydroxyphenyl)-N Ј-(2-methoxyphenyl)oxamide 6, N-(2-hydroxyphenyl)-N Ј-phenethyloxamide 7, (1S,2R)-(؊)-N-(2-hydroxyphenylcarbamoylcarbonyl)norephedrine 8, (1R,2S)-(؊)-N-(2-hydroxyphenylcarbamoylcarbonyl) 9, ethyl N-(2-hydroxyphenyl)oxalamate 10 and ethyl N-(2-methoxyphenyl)oxalamate 11. The structures were established by 1 H, 13 C, 15 N and variable temperature NMR spectroscopy. Compounds 1-4 and 6-11 are stabilized by intramolecular three-center hydrogen bonding between the amide proton and two oxygen atoms. The 1 H NMR / T value of the amide proton correlates with the 15 N NMR chemical shift. The X-ray diffraction molecular structures of 1 and 11 showed a planar conformation with trans configuration in the solid state, corresponding to the preferred conformation found in solution.

Thermodynamic characterization of three centered hydrogen bond using o-aromatic amides, oxalamates and bis-oxalamides as model compounds

“…Results are listed in Table 3 In oxalamate and bis-oxalamide systems, the participation of C(6)-H6⋅⋅⋅OCNH hydrogen bonding as a cooperative interaction in THB formation, has been noted in both solution and in the solid state. 18 In solution, the δH(6) is shifted to high frequencies by the local deshielding effect of the amide carbonyl group, which is most of the time pointing out to this hydrogen atom as the N-H mobility is smaller. This effect has been known for a long time for ortho-substituted anilides.…”

“…In this solvent, temperature gradient values of amide N-H chemical shift (∆δ/∆T) below 2 ppb are considered as indicative of solvent shielded or non-exposed systems. 17 Alternatively, for small systems ∆δ/∆T values, 18 as well as solvent induced gradients of the NH chemical shift and N-H IR stretching frequencies 12 have been related to the strength of the three centered hydrogen bonding interaction, however, the energy involved has not been estimated. Our previous studies on oxalamide derivatives have demonstrated the existence of THB both in DMSO solution 1 and in solid state 18 and have also established the role of tautomeric equilibria on the stability of these systems.…”

Energetics and cooperativity in three-center hydrogen bonding interactions. I. Diacetamide-X dimers (X=HCN, CH3OH)

“…2 The existence of three-center H-bond interactions in solution has also been experimentally demonstrated. 3 Two types of three-center H-bond interaction can be distinguished: ͑a͒ one that involves an H atom and two acceptor atoms ͑denoted A 1 HA 2 ), and ͑b͒ one that involves an acceptor atom and two H atoms ͑denoted H 1 AH 2 ). 4 These two possibilities are depicted in Fig.…”

New bis-oxalamides from trans-1,2-diaminocyclohexane

“…Experimental and theoretical studies have demonstrated that intramolecular hydrogen bonds in oxalamides determine their geometry and conformation whereas intermolecular hydrogen bonds increase their stability. [1][2][3] Due to these interactions, oxalamides are applied in diverse areas such as artificial receptors for biological recognition, 4 in engineering and crystal design 5 and in organogels formation. 6 Recently, oxalamide derivatives were identified as HIV-1 inhibitors.…”