Theoretical and NMR Studies of Deuterium Isotopic Perturbation of Hydrogen Bonding in Symmetrical Dihydroxy Compounds

• Published in: Journal of organic chemistry 2010-03, Vol.75 (5), p.1331-1342
• Main Authors: O'Leary, Daniel J, Hickstein, Daniel D, Hansen, Bjarke K. V, Hansen, Poul Erik
• Format: Article
• Language: English
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Chemistry; Exact sciences and technology; Labelled compounds chemistry; Noncondensed benzenic compounds; Organic chemistry; Preparations and properties; Reactivity and mechanisms
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo902075z

Deuterium equilibrium isotope effects (EIEs) for a cage diol and 2,6-dihydroxyacylaromatics and complexes thereof containing intra- or intermolecular hydrogen bonds have been calculated using harmonic and anharmonic vibrational frequencies using Gaussian ’03 and the HF, B3LYP, and MP2 levels of theory. The predicted isotope effects have been compared with experimental NMR data, and the origins of the isotope effects have been characterized in terms of zero-point vibrational energy differences and enthalpic and entropic contributions to the free energy difference between labeled species. Reliable free energy predictions based upon harmonic frequencies were found for systems whose isotope effects are governed by bond stretching effects and for systems whose isotope effects are determined by low-frequency vibrational modes. In contrast, thermochemical predictions based upon anharmonic frequencies were found to be far less consistent. Vibrational entropy is predicted to play an important role in modulating and, in some cases, governing isotopic site preferences in hydroxyl-derived intra- and intermolecular hydrogen bonds.