Intra- vs. intermolecular hydrogen bonding: dimers of alpha-hydroxyesters with methanol

Abstract

Intermolecular hydrogen bonding competes with an intramolecular hydrogen bond when methanol binds to an alpha-hydroxyester. Disruption of the intramolecular OH...O=C contact in favour of a cooperative OH...OH...O=C sequence is evidenced by FTIR spectroscopy for the addition of methanol to the esters methyl glycolate, methyl lactate and methyl alpha-hydroxyisobutyrate in seeded supersonic jet expansions. Comparison of the OH stretching modes with quantum-chemical harmonic frequency calculations and 18O labelling of methanol unambiguously prove the insertion of methanol into the intramolecular hydrogen bond. This is in marked contrast to UV/IR hole burning studies of the homologous system methyl lactate: (+/-)-2-naphthyl-1-ethanol, where only addition complexes were found and the intramolecular hydrogen bond was conserved. This switch in hydrogen bond pattern from aliphatic to aromatic heterodimers is thought to reflect not only a kinetic propensity but also a thermodynamic preference for addition complexes when dispersion forces become more important in aromatic systems.

Chirality Recognition between Neutral Molecules in the Gas Phase

“…However, the structure of the (1S,2S)-N-methylpseudoephedrine:(AE)-MeLac complex has not been determined experimentally and the only experimental evidence of insertion complexes involving syn lactates is provided by the methanol:MeLac dimer studied in a slit jet experiment by direct FTIR absorption. [147] Their IR spectrum is characterized by two features which are shifted to the red of both the lactate and methanol absorption. This spectrum indicates formation of an OH···OH bond and its reinforcement through cooperative effects.…”

Chirality-dependent sublimation of -(trifluoromethyl)-lactic acid: Relative vapor pressures of racemic, eutectic, and enantiomerically pure forms, and vibrational spectroscopy of isolated (S,S) and (S,R) dimers

“…First attempts to expand the room temperature vapor in a supersonic slit nozzle of 600 mm length [33] failed due to the limited volatility. Expansion in a heated nozzle (see Section 2.4) at temperatures between 323 and 363 K resulted in the jet spectra shown in Figs.…”

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

“…Useful information can be obtained from experimental gas-phase hydration/solvation studies augmented with theoretical calculations [108][109][110][111][112][113][114][115][116] or specific theoretical calculations for hydrated amino acid side chains, nucleotid base and sugar models [117][118][119][120][121].…”