The conformational preferences of 3-hydroxytetrahydropyran (1) were evaluated using infrared and nuclear magnetic resonance spectroscopic data in solvents of different polarities. Theoretical calculations in the isolated phase and including the solvent effect were performed, showing that the most stable conformations for compound 1 are those containing the substituent in the axial and equatorial orientations. The axial conformation is more stable in the isolated phase and in a nonpolar solvent, while the equatorial conformation is more stable than the axial in polar media. The occurrence of intramolecular hydrogen-bonded O-H⋯O in the axial conformer was detected from infrared spectra in a nonpolar solvent at different concentrations. Our attempt to evaluate this interaction using population natural bond orbital and topological quantum theory of atoms in molecules analyses failed, but topological noncovalent interaction analysis was capable of characterizing it. © 2014 American Chemical Society.1181527942800Eliel, E.L., Samuel, H.W., Doyle, M.P., (2001) Basic Organic Stereochemistry, , Wiley-Interscience: New YorkCortéz-Guzman, F., Hernández-Trujillo, J., Cuevas, G., The Nonexistence of Repulsive 1,3-diaxial Interactions in Monosubstituted Cyclohexanes (2003) J. Phys. Chem. A, 107, pp. 9253-9256Ribeiro, D.S., Rittner, R., The Role of Hyperconjugation in the Conformational Analysis of Methylcyclohexane and Methylheterocyclohexanes (2003) J. Org. Chem., 68, pp. 6780-6787Taddei, F., Kleinpeter, E., The Anomeric Effect in Substituted Cyclohexanes. I. The Role of Hyperconjugative Interactions and Steric Effect in Monosubstituted Cyclohexanes (2004) J. Mol. Struct.: THEOCHEM, 683, pp. 29-41Freitas, M.P., Tormena, C.F., Rittner, R., Interaction in trans-2-Halocyclohexanols-an Infraredand Theoretical Study (2001) J. Mol. Struct., 570, pp. 175-180Freitas, M.P., Tormena, C.F., Oliveira, P.R., Rittner, R., Halogenated Six-Membered Rings: A Theoretical Approach for Substituent Effects in Conformational Analysis (2002) J. Mol. Struct.: THEOCHEM, 589-590, pp. 147-151Freitas, M.P., Tormena, C.F., Luizar, C., Ferreira, M.M.C., Rittner, R., Substituent Interactions in trans -2-Substituted Methoxycyclohexanes: An Explanation to the Conformational Behaviour in a Chemometric and Theoretical View (2002) J. Mol. Struct. THEOCHEM, 618, pp. 219-224Freitas, M.P., Tormena, C.F., Rittner, R., Abraham, R.J., Conformational Analysis of trans -2-Halocyclohexanols and their Methyl Ethers: A 1H NMR, Theoretical and Solvation Approach (2003) J. Phys. Org. Chem., 16, pp. 27-33Freitas, M.P., Tormena, C.F., Rittner, R., Abraham, R.J., Conformational Properties of trans -2-Halo-acetoxycyclohexanes: 1H NMR, Solvation and Theoretical Investigation (2005) J. Mol. Struct., 734, pp. 211-217Freitas, M.P., Rittner, R., Tormena, C.F., Abraham, R.J., Conformational Analysis and Stereoelectronic Effects in trans -1,2-Dihalocyclohexanes: 1H NMR and Theoretical Investigation (2005) Spectrochim. Acta, Part A, 61, pp. 1771-1776Bocca, C.C., Basso, E.A., Fiorin, B.C., Tormena, C.F., Dos Santos, F.P., Conformational Behavior of cis -2-Methoxy, cis -2-Methylthio, and cis -2-Methylselenocyclohexanol: A Theoretical and Experimental Investigation (2006) J. Phys. Chem. A, 110, pp. 9438-9442Cedran, J.C., Dos Santos, F.P., Basso, E.A., Tormena, C.F., Conformational Preferences of 2-Methoxy, 2-Methylthio, and 2-Methylselenocyclohexyl- N, N -dimethylcarbamate: A Theoretical and Experimental Investigation (2007) J. Phys. Chem. A, 111, pp. 11701-11705Basso, E.A., Abiko, L.A., Gauze, G.F., Pontes, R.M., Conformational Analysis of cis -2-HalocyclohexanolsSolvent Effects by NMR and Theoretical Calculations (2011) J. Org. Chem., 76, pp. 145-153Silla, J.M., Cormanich, R.A., Duarte, C.J., Freitas, M.P., Ramalho, T.C., Barbosa, T.M., Santos, F.P., Rittner, R., Alkyl Group Effect on the Conformational Isomerism of trans -2-Bromoalkoxycyclohexanes Analyzed by NMR Spectroscopy and Theoretical Calculation (2011) J. Phys. Chem. A, 115, pp. 10122-10127Basso, E.A., Kaiser, C., Rittner, R., Lambert, J.B., Axial Equatorial Proportions for 2-Substituted Cyclohexanones (1993) J. Org. Chem., 58, pp. 7865-7869Freitas, M.P., Rittner, R., Tormena, C.F., Abraham, R.J., Conformational Analysis of 2-Bromocyclohexanone. A Combined NMR, IR, Solvation and Theoretical Approach (2001) J. Phys. Org. Chem., 14, pp. 317-322Yoshinaga, F., Tormena, C.F., Freitas, M.P., Rittner, R., Abraham, R.J., Conformational Analysis of 2-Halocyclohexanones: An NMR, Theoretical and Solvation Study (2002) J. Chem. Soc., Perkin Trans.2, pp. 1494-1498Freitas, M.P., Tormena, C.F., Garcia, J.C., Rittner, R., Abraham, R.J., Basso, E.A., Santos, F.P., Cedran, J.C., NMR, Solvation and Theoretical Investigations of Conformational Isomerism in 2-X-cyclohexanones (X=NMe2, OMe, SMe and SeMe) (2003) J. Phys. Org. Chem., 16, pp. 833-838Coelho, J.V., Freitas, M.P., Tormena, C.F., Rittner, R., On the4 JHH Long-range Coupling in 2-Bromocyclohexanone: Conformational Insights (2009) Magn. Reson. Chem., 47, pp. 348-351Coelho, J.V., Freitas, M.P., Ramalho, T.C., Martins, C.R., Bitencourt, M., Carmanich, R.A., Tormena, C.F., Rittner, R., The Case of Infrared Carbonyl Stretching Intensities of 2-Bromocyclohexanone: Conformational and Intermolecular Interaction Insights (2010) Chem. Phys. Lett., 494, pp. 26-30Anizelli, P.R., Vilcachagua, J.D., Cunha Neto, A., Tormena, C.F., Stereoelectronic Interaction and Their Effects on Conformational Preference for 2-Substituted Methylenecyclohexane: An Experimental and Theoretical Investigation (2008) J. Phys. Chem. A, 112, pp. 8785-8789Alabugin, I.V., Gilmore, K.M., Peterson, P.W., Hyperconjugation (2011) Wiley Interdiscip. Rev.: Comput. Mol. Sci., 1, pp. 109-141Ha, S., Gao, J., Tidor, B., Brady, J.W., Karplus, M., Solvent Effect on the Anomeric Equilibrium in D-glucose: A Free Energy Simulation Analysis (1991) J. Am. Chem. Soc., 113, pp. 1553-1557Cramer, C.J., Anomeric and Reverse Anomeric Effects in the Gas Phase and Aqueous Solution (1992) J. Org. Chem., 57, pp. 7034-7043Mo, Y., Computational Evidence that Hyperconjugative Interactions are not Responsible for the Anomeric Effect (2010) Nat. Chem., 2, pp. 666-671Huang, Y., Zhong, A.-G., Yang, Q., Liu, S., Origin of Anomeric Effect: A Density Functional of Steric Analysis (2011) J. Chem. Phys., 134, pp. 84103-84109Bauerfeldt, G.F., Cardozo, T.M., Pereira, M.S., Da Silva, C.O., The Anomeric Effect: The Dominance of Exchange Effects in Closed-Shell Systems (2013) Org. Biomol. Chem., 11, pp. 299-308Cocinero, E.J., Çarçabal, P., Vaden, T.D., Simons, J.P., Davis, B.G., Sensing the Anomeric Effect in a Solvent-Free Environment (2011) Nature, 469, pp. 76-80Freitas, M.P., Simultaneous Gauche and Anomeric Effects in α-Substituted Sulfoxides (2012) J. Org. Chem., 77, pp. 7607-7611Freitas, M.P., The Anomeric Effect on the Basis of Natural Bond Orbital Analysis (2013) Org. Biomol. Chem., 11, pp. 2885-2890Sugai, T., Lkeda, H., Ohta, H., Biocatalytic Approaches to Both Enantiomers of (2R*,3S*)-2- Allyloxy-3,4,5,6-tetrahydro-2H-pyran-3-ol (1996) Tetrahedron, 52, pp. 8123-8134Kosjek, B., Nti-Gyabaah, J., Telari, K., Dunne, L., Moore, J.C., Preparative Asymmetric Synthesis of 4,4-Dimethoxytetrahydro-2 H -pyran-3-ol with a Ketone Reductase and in Situ Cofactor Recycling using Glucose Dehydrogenase (2008) Org. Process Res. Dev., 12, pp. 584-588Sugawara, K., Imanishi, Y., Hashiyama, T., Efficient and Practical Synthesis of both Enantiomers of 6-Silyloxy-3-pyranone Derivatives (2000) Tetrahedron: Asymmetry, 11, pp. 4529-4535Chan, W.N., Evans, J.M., Hadley, M.S., Morgan, H.K.A., Stean, T.O., Thompson, M., Upton, N., Vong, A.K., Synthesis of Novel trans -4-(Substitutedbenzamido)-3,4-dihydro-2 H -benzo[ b ]-pyran-3-ol Derivatives as Potential Anticonvulsant Agents with a Distinctive Binding Profile (1996) J. Med. Chem., 39, pp. 4537-4539Sasaerila, Y., Gries, R., Gries, G., Khaskin, G., King, S., Takács, S., Hardi, Sex Pheromone Components of Male Tirathabamundella (Lepidoptera: Pyralidae) (2003) Chemoecology, 13, pp. 89-93Barker, S.A., Brimacombe, J.S., Foster, A.B., Whiffen, D.H., Zweifel, G., Intramolecular Hydrogen Bonding in some Monohydroxy Derivatives of Tetrahydrofuran, Tetrahydropyran and 1,3-dioxan (1959) Tetrahedron, 7, pp. 10-18Møller, C., Plesset, M.S., Note on an approximation treatment for many-electron systems (1934) Phys. Rev., 46, pp. 618-622Head-Gordon, M., Pople, J.A., Frisch, M.J., MP2 energy evaluation by direct methods (1988) Chem. Phys. Lett., 153, pp. 503-506Purvis III, G.D., Bartlett, R.J., A full coupled-cluster singles and doubles model: The inclusion of disconnected triples (1982) J. Chem. Phys., 76, pp. 1910-1918Weinhold, F., Natural Bond Orbital Analysis: A Critical Overview of Relationships to Alternative Bonding Perspectives (2012) J. Comput. Chem., 33, pp. 2363-2379Bader, R.F.W., (1990) Atoms in Molecules: A Quantum Theory, , Clarendon: Oxford, U.KJohnson, E.R., Keinan, S., Mori-Sánchez, P., Contreras-García, J., Cohen, A.J., Yang, W., Revealing Noncovalent Interactions (2010) J. Am. Chem. Soc., 132, pp. 6498-6506Frisch, M.J., (2009) Gaussian 09, , revision D.01Gaussian, Inc. Wallingford, CTGeertsen, J., Oddershede, J., 2nd-Order Polarization Propagator Calculations of Indirect Nuclear Spin-Spin Coupling Tensors in the Water Molecule (1984) Chem. Phys., 90, pp. 301-311Enevoldsen, T., Oddershede, J., Sauer, S.P.A., Correlated Calculations of Indirect Nuclear Spin-Spin Coupling Constants using Second-Order Polarization Propagator Approximations: SOPPA and SOPPA(CCSD) (1998) Theor. Chem. Acc., 100, pp. 275-284Sauer, S.P.A., Second-Order Polarization Propagator Approximation with Coupled-Cluster Singles and Doubles Amplitudes-SOPPA(CCSD): The Polarizability and Pyperpolarizability of Li- (1997) J. Phys. B: At., Mol. Opt. Phys., 30, pp. 3773-3780(2011), http://daltonprogram.org, Dalton2011, A Molecular Electronic Structure ProgramBarone, V., (1996) Recent Advances in Density Functional Methods, Part i, , Chong, D. P. World Scientific Publ. Co. SingaporeGlendening, E.D., Badenhoop, J.K., Reed, A.E., Carpenter, J.E., Bohmann, J.A., Morales, C.M., Landis, C.R., Weinhold, F., (2013) NBO 6.0, , Theoretical Chemistry Institute, University of Wisconsin, Madison: Madison, WI, Program implemented in the Gaussian 09 packageKeith, T.A., (2011) AIMALL, , aim.tkgristmill.comh, version 11.10.16TK Gristmill Software: Overland Park, KSContreras-García, J., Johnson, E.R., Keinan, S., Chaudret, R., Piquemal, J.-P., Beratan, D.N., Yang, W., NCIPLOT: A Program for Plotting Noncovalent Interaction Regions (2011) J. Chem. Theory Comput., 7, pp. 625-632Zweifel, G., Plamondon, J., Hydroboration of Dihydropyrans and Dihydrofurans (1970) J. Org. Chem., 35, pp. 898-902Marenich, A.V., Cramer, C.J., Truhlar, D.G., Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions (2009) J. Phys. Chem. B, 113, pp. 6378-6396Abraham, R.J., Jones, A.D., Warne, M.A., Rittner, R., Tormena, C.F., Conformational Analysis. Part 27. NMR, Solvation and Theoretical Investigation of Conformational Isomerism in Fluoro- and l,l-difluoro-acetone (1996) J. Chem. Soc., Perkin Trans 2, pp. 533-539Helgaker, T., Jaszuński, M., Pecul, M., The Quantum-Chemical Calculation of NMR Indirect Spin-Spin Coupling Constants (2008) Prog. Nucl. Magn. Reson. Spectrosc., 53, pp. 249-268Conley, R.T., (1972) Infrared Spectroscopy, pp. 129-131. , 2 nd ed. Allyn and Bacon: BostonLane, J.R., Contreras-García, J., Piquemal, J.-P., Miller, B.J., Kjaergaard, H.G., Are Bond Critical Points Really Critical for Hydrogen Bonding? (2013) J. Chem. Theory Comput., 9, pp. 3263-3266Grabowski, S.J., What Is the Covalency of Hydrogen Bonding? (2011) Chem. Rev., 111, pp. 2597-2625