Intermolecular steric hindrance in 7-acylamino-[1H]-2-oxo-1,8-naphthyridines: NMR, ESI-MS, IR, and DFT calculation studies

Abstract

Intermolecular interactions of 7-(RCONH)-[1H]-2-oxo-1,8-naphthyridines (R = Me, Et, i-Pr, t-Bu, 1-adamantyl (1-Ad), CF 3 , and C 2 F 5 ) containing ADAD quadruple hydrogen bonding motif were studied by liquid and solid state NMR, ESI-MS, IR, and DFT calculations. 1 H NMR was used to determine the dimerization constants of i-Pr and 1-Ad congeners in CDCl 3 . 13 C and 15 N crosspolarization (CP) magic angle spinning (MAS) NMR data suggest that compounds possess similar solid state structures. Further, mass spectral data reveal that in gas phase both Me and 1-Ad derivatives form also multimers due to lack of competitive solvent interactions. The structures of the gas phase multimers depend on the size of the alkyl group. These results are in agreement with quantum chemical calculations. Geometry optimization and 1 H NMR spectra show that in dimers that carry bulky alkyl groups (t-Bu and 1-Ad) certain hydrogen bonds are weaker than in Me, Et, and i-Pr derivatives while strong electron acceptors, CF 3 and C 2 F 5 , deshields hydrogen bonded protons but creates significant electronic F/O repulsion yielding lowering of the energy of interaction. The influence of steric effect on dimerization of quadruply hydrogen bonded dimers was correlated with the Taft E s values.

Supramolecular Mimic for Bottlebrush Polymers in Bulk

“…This shows that 2 in its dimeric form has a weak C–H···OC hydrogen bond that can solidify the conformational form (Figure ) and prevent it from rotating to create the forms with intramolecular N–H···N H-bonding. Although this effect is relatively weak, intermolecular or intramolecular H-bonding of C–H···N/O has been reported earlier. , The change in the chemical shift (8.19–6.83 ppm) of the aromatic proton in the proximity of OC (dark blue) is also induced due to an anisotropic deshielding cone of OC in full agreement with similar heterocyclic ureas. ,, This interaction is more probable in the case of the hydrogen-bonded dimer in which rotation is limited due to six hydrogen bonds with the other monomer. Therefore, when the intermolecular H-bonding is broken, the rotation occurs implying that in the monomeric form, keto tautomer is more stable, whereas the keto dimer is a stable conformation when the two stickers are in close proximity to each other, in nonpolar solvents or the melt state.…”

“…This is also consistent with our 1 H NMR analysis showing that in the dimerized form in chloroform (or in vacuum), keto form is the most stable dimer/conformer. This value for similar naphthyridine-based compounds with DADA-type H-bonding was only −16.55 to −23.58 kcal mol –1 , 36 implying that the bifurcated urea hydrogen bond plays a significant role in the dimerization of 2 .…”

“…34,35 The change in the chemical shift (8.19–6.83 ppm) of the aromatic proton in the proximity of O=C (dark blue) is also induced due to an anisotropic deshielding cone of O=C in full agreement with similar heterocyclic ureas. 33,34,36 This interaction is more probable in the case of the hydrogen-bonded dimer in which rotation is limited due to six hydrogen bonds with the other monomer. Therefore, when the intermolecular H-bonding is broken, the rotation occurs implying that in the monomeric form, keto tautomer is more stable, whereas the keto dimer is a stable conformation when the two stickers are in close proximity to each other, in nonpolar solvents or the melt state.…”

The influence of CH bond polarization on the self-association of 2-acylaminopyrimidines by NH/CH···O/N interactions: XRD, NMR, DFT, and AIM study

“…It has been shown how hydrogen bonding can be used in designing the shape of aggregate [5][6][7] in solution and in solid state [8]. Generally, non-covalent intermolecular interactions are influenced by steric effects [9][10][11][12], electronic repulsion [11,13], position of the heteroatoms in the ring [14][15][16], and cooperative effects [17]. The atoms able to compete for hydrogen bonds (basic or acidic centers) are responsible for the conformational flexibility of NH-CO bond in amides [18][19][20].…”

Thetrans/cisphotoisomerization in hydrogen bonded complexes with stability controlled by substituent effects: 3-(6-aminopyridin-3-yl)acrylate case study

“…The fact that double hydrogen bonded neutral molecules barely form dimers in polar solvent is in agreement with the studies of 2-acylamino-1,8-naphthyridin-7-ones that are stabilized in its dimeric form by quadruple hydrogen bonding (in CDCl 3 ). 38 The same hydrogen-bonding pattern is present in the cis form of 1, but both, the mentioned naphthyridine derivative and cis-1, do not dimerize in DMSO. Since anions [39][40][41][42][43] are able to interact with urea moiety in polar and highly competitive solvents, 7 the tetrabutylammonium salt 2 was used in association (vide infra) experiments.…”