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

Abstract

The study of the thermodynamic properties and cooperativity involved in three centered hydrogen (THB) bond formation using aromatic ortho-A substituted amides, oxalamates and bisoxalamides (A = H, OMe, F, CH 2 OH, NO 2 , COCH 3 ) as model molecules is reported. ∆H° and ∆S° associated with disruption of intramolecular hydrogen bonding by solvent were estimated using temperature dependence data of the N-H chemical shift. The results suggest that the influence of the A group is more important when electron-withdrawing, increasing both the enthalpy and entropy with an important contribution from conformational changes. The data allowed the estimation of the Ph=NH + rotational barrier of 14.0 kJ mol -1 in the amide and 16.7-18.0 kJ mol -1 in oxalyl moiety. Correlations between ∆H° and ∆S° with NH temperature gradients predicted an enthalpy change of 18.7(1.0) and 24.4(1.7) kJ mol -1 for the energy required to break a full THB bond (A⋅⋅⋅H⋅⋅⋅O=C) and entropy differences between the non hydrogen bonded and hydrogen bonded state of 42.0(4.7) and 61.9(11) J mol -1 K -1 in oxalamate and bis-oxalamide series, respectively, in agreement with the participation of cooperative effects.

Pseudocyclic Form of 4-Hydroxypyrrolidine-2-carboxanilide Podands with Trioxyethylene Chain: Modeling, Conformational Search, and NMR Analysis

“…4-Hydroxypyrrolidine-2-carboxanilide podands 1 and 2 have a topology similar to the previously studied aromatic ortho-substituted anilides 3 − (Scheme ). They are capable of forming two- and three-center intramolecular HBs between the amide proton H a and electronegative heteroatoms of R and R′ groups.…”

“…Information about HBs is usually obtained from NMR experiments by tracking changes in the CSs of protons of polar groups with a change in the polarity of the solvent, with a change in the concentration of a solution (NMR titration experiments), and under temperature-induced perturbations …”

“…They are capable of forming two- and three-center intramolecular HBs between the amide proton H a and electronegative heteroatoms of R and R′ groups. Some important parameters of CSs in 1 H NMR spectra of anilides 3a,b in DMSO- d 6 are listed in Scheme . The δH a value in such systems depends on the electron-donating or electron-withdrawing properties of the functional groups R and R′, on the solvent nature affecting the tautomeric equilibrium of the CONH fragment, and on the stability of the HB in the five or six-membered pseudocyclic structure.…”

“…As was demonstrated earlier by quantum-chemical calculations, the H a atom in the conformers 1a and 1c (Scheme and Figure ) with the highest correlation between calculated and experimental 1 H NMR spectra is oriented toward the O atom in an 2-alkoxyphenyl moiety and toward the N p atom in each branch heterocycle due to the intramolecular HB (Figure a). The formation of three-center intramolecular HB − leads to H a double deshielding from the side of close electronegative heteroatoms, and it is the reason for its downfield shift of 10.30 ppm in DMSO- d 6 in the experimental 1 H NMR spectrum (Table ). At the same time, the shift of δH Ph 6 toward higher frequencies up to 8.28 ppm during the three-center intramolecular HB formation can be explained by the local deshielding effect of amide group, according to the literature data for ortho-substituted anilides .…”

“…The formation of three-center intramolecular HB − leads to H a double deshielding from the side of close electronegative heteroatoms, and it is the reason for its downfield shift of 10.30 ppm in DMSO- d 6 in the experimental 1 H NMR spectrum (Table ). At the same time, the shift of δH Ph 6 toward higher frequencies up to 8.28 ppm during the three-center intramolecular HB formation can be explained by the local deshielding effect of amide group, according to the literature data for ortho-substituted anilides . The downfield (δH Ph 6 ) and upfield (δH a ) shifts by a small amount (ΔδH Ph 6 equal to −0.08 and ΔδH a equal to 0.11 ppm), which were observed when the solvent polarity changed during the transition from DMSO- d 6 to CDCl 3 , are characteristic signs of the formation of three-center intramolecular HB (Table ).…”