Interplay between Intramolecular Resonance-Assisted Hydrogen Bonding and Aromaticity ino-Hydroxyaryl Aldehydes

Abstract

In this work, we analyze a series of o-hydroxyaryl aldehydes to discuss the interrelation between the resonance-assisted hydrogen bond (RAHB) formation and the aromaticity of the adjacent aromatic rings. As compared to the nonaromatic reference species (malonaldehyde), the studied compounds can be separated into two groups: first, the set of systems that have a stronger RAHB than that of the reference species, for which there is a Kekulé structure with a localized double CC bond linking substituted carbon atoms; and second, the systems having a weaker RAHB than that of the reference species, for which only pi-electrons coming from a localized Clar pi-sextet can be involved in the RAHB. As to aromaticity, there is a clear reduction of aromaticity in the substituted ipso ring for the former group of systems due to the formation of the RAHB, while for the latter group of species only a slight change of local aromaticity is observed in the substituted ipso ring.

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…A special class of intramolecular hydrogen bonds predicted to be very strong because the neutral donor and acceptor atoms are linked by a system of π-conjugated double bonds was defined by Gilli [129,130] as a resonance-assisted hydrogen bond (RAHB). The investigations by many authors [125,131,132] have established that RAHB systems by their aromaticity numerical descriptors (aromaticity indices [125]) fulfill (at least partially) the conditions of the aromatic π-electron delocalization; therefore, they can be treated as quasiaromatic.…”

“…This approach cannot be used to study intramolecular interactions, and despite the fact that the hydrogen bonds are qualitatively well understood, [18,122,124,125,183] it is generally admitted that a simple method of calculation and quantitative data is needed [184]. The energy of such optimized structures stabilized by the intramolecular hydrogen bond was used to estimate its strength by different comparative methods: cis−trans analysis [132,185,186], isodesmic reactions [187] and conformational analysis with gradual or total rotation of the H-bond donor or acceptor [138,188,189]. The first of these methods is simplistic, because the energetic stabilization of the H-bonded conformer includes several contributions, such as the balance between attractive and repulsive terms, steric constraints of bulky groups, conjugation and other interactions, and this situation changes radically after turning out of the hydroxyl group.…”

Self-assembly mechanism based on charge density topological interaction energies

“…The second effect is the presence of Resonance-Assisted Hydrogen Bonds (RAHBs), which are known to decrease the aromaticity of the adjusted phenyl ring, due to strong interrelation between the π-electron delocalization and the strength of the hydrogen bonds which form the RAHB rings. These phenomena are well known and have been described extensively elsewhere [31,49,50]. At first glance, it seems reasonable that the rather small twist angle of the carboxylate groups is stabilized due to intramolecular C-H…O interactions, forming a fivemembered ring.…”

“…At first glance, it seems reasonable that the rather small twist angle of the carboxylate groups is stabilized due to intramolecular C-H…O interactions, forming a fivemembered ring. The geometry criterion for H-bonds suggests that each carboxylate group could participate in (up to) two of these interactions, which are classified as RAHBs [49]. Surprisingly, the presence of these H-bonding interactions could not be confirmed from the total charge density following topological analysis.…”

Electronic and Molecular Structures of Heteroradialenes: A Combined Synthetic, Computational, Spectroscopic, and Structural Study Identifying IR Spectroscopy as a Simple but Powerful Experimental Probe

“…In salicylaldehyde, tautomer IX is more stable than XII that is no longer aromatic (Scheme 2) [19,20]. However, the molecular geometries determined via electron diffraction in conjunction with DFT calculations reveal that also in these systems the resonance structure X has strong contributions to the overall resonance hybride so that the hydrogen bond is also resonance-assisted [19,21,22]. The same holds true for the salicylaldimine derivative.…”