Association ofN-(Pyridin-2-yl),N′-substituted Ureas with 2-Amino-1,8-naphthyridines and Benzoates: NMR and Quantum Chemical Studies of the Substituent Effect on Complexation

Abstract

Association of four N-(pyridin-2-yl),N'-R(1)-ureas (R(1) = ethyl, n-butyl, phenyl, and tert-butyl) with substituted 2-amino-1,8-naphthyridines and benzoates were studied by (1)H NMR spectroscopic titrations and quantum chemical calculations. The benzoates and 2-amino-1,8-naphthyridines were selected as representatives of double and triple hydrogen bonding counterparts, respectively. The classical substituent effect on the association was studied. A prerequisite and a crucial step for the complex formation was the breaking of the intramolecular hydrogen bond in urea derivatives. The QTAIM calculation method was employed to explain the hydrogen bonding within complexes. In the case of benzoates carrying an electron-donating substituent the experimental findings were explained by the formation of two complexes. These observations were rationalized by the electronic repulsions between atoms in a close proximity and further verified by calculations. Single-crystal X-ray diffraction was used to confirm the structure of studied ureas in the crystalline state. These results are in line with the solution studies of self-association of ureas.

Substituent effects in hydrogen bonding: DFT and QTAIM studies on acids and carboxylates complexes with formamide

“…Also, as before, the correlation is higher for a strong interaction (NH · · · O) than for a weak one (CH · · · O). It was recently shown [18] that the interaction with substituted benzoates is driven by the character of the substituent when associated with urea by two, close in energy NH · · · O hydrogen bonds. Here the NH · · · O hydrogen bond is much stronger (more than six times) than the CH · · · O interaction.…”

“…The M05 functional suggested for non-covalent interactions [40, 41] was used together with the 6-311+G(2d,2p) basis set as in previous publications [18, 21, 22]. The use of the diffuse functions is crucial for describing the anionic specie, while polarization functions are used to properly describe the hydrogen bonding.…”

“…The use of the diffuse functions is crucial for describing the anionic specie, while polarization functions are used to properly describe the hydrogen bonding. Optimizations were performed with the use of PCM model of solvation [42] in chloroform since in previous publications such treatment was in agreement with experimental results [18, 21, 22]. For all optimized structures the frequency calculations were ran to check if the geometry is in energy minima (only positive frequencies were obtained).…”

“…However, in supramolecular chemistry there are several possibilities to tune the non-covalent interactions [16, 17]. These are the electronic substituent effect [18–20, 17], steric effect [21–24], and intermolecular electronic repulsion [25] to mention a few. Although very good reviews on tuning the molecular properties and thus influence on their interactions has been published there are still not so many extensive works in the topic of pure substituent effect in simple associates.…”

“…This is especially true for studies taking into account more than five various substituents. Recently it was shown that the association of substituted benzoates with heterocyclic urea derivatives preceded by breaking the intramolecular hydrogen bond is driven by the character of the substituent [18]. In compounds that are able to form a intramolecular hydrogen bond such a conformation is preferred.…”