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), CF₃, and C₂F₅) containing ADAD quadruple hydrogen bonding motif were studied by liquid and solid state NMR, ESI-MS, IR, and DFT calculations. ¹H NMR was used to determine the dimerization constants of i-Pr and 1-Ad congeners in CDCl₃. ¹³C and ¹⁵N cross-polarization (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 ¹H 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, CF₃ and C₂F₅, 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.