Spectrochimica Acta Part A 78 (2011) 1599–1605 Contents lists available at ScienceDirect Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy journal homepage: www.elsevier.com/locate/saa Influence of OH···N and NH···O inter- and intramolecular hydrogen bonds in the conformational equilibrium of some 1,3-disubstituted cyclohexanes through NMR spectroscopy and theoretical calculations Paulo R. de Oliveira a , Renan V. Viesser a , Palimécio G. Guerrero Jr. a , Roberto Rittner b,∗ a Laboratory of Organic Synthesis and Natural Products, Department of Chemistry and Biology, Federal University of Technology-Paraná, Av. Sete de Setembro 3165, 80230-901 Curitiba, PR, Brazil b Physical Organic Chemistry Laboratory, Chemistry Institute, State University of Campinas, POB 6154, 13083-970 Campinas, SP, Brazil article info Article history: Received 8 November 2010 Received in revised form 13 January 2011 Accepted 7 February 2011 Keywords: Conformational analysis NMR spectroscopy Theoretical calculations Intramolecular hydrogen bond Aminocyclohexanols abstract The analysis of concentration effects in the 1 H NMR data of cis-3-aminocyclohexanol (ACOL) showed that its diequatorial conformer changes from 60% at 0.01 mol L -1 to 70% at 0.40 mol L -1 in acetone-d 6 . A similar increase was also observed for the diequatorial conformer of cis-3-N-methylaminocyclohexanol (MCOL), from 32% (CDCl 3 0.01 mol L -1 ) to 55% (CDCl 3 0.40 mol L -1 ). The increase in solvent basicity leads to a large stabilization effect for the diequatorial conformer of both compounds too. For ACOL, it changes from 47% (G eqeq–axax = 0.06 kcal mol -1 ) in CCl 4 to 93% (G eqeq–axax = -1.53 kcal mol -1 ) in DMSO, while for MCOL it goes from 7% (G eqeq–axax = 1.54 kcal mol -1 ) in CCl 4 to 82% (G eqeq–axax = -0.88 kcal mol -1 ) in pyridine-d 6 . These results indicate that the intramolecular hydrogen bonds (IAHB) OH···N and NH···O stabilize the diaxial conformers of these compounds in a non-polar solvent. For cis-3-amino-1-methoxycyclohexane (ACNE) and cis-3-N-methylamino-1-methoxy-cyclohexane (MCNE) no changes were observed in equilib- rium with the variation of solvent polarity. These results indicate for the first time that the IAHB NH···O is not strong enough to stabilize the diaxial conformer of these compounds and that the conformation equilibria of the cis isomers of compounds ACOL and MCOL are influenced only by the IAHB OH···N. More- over, the presence of a secondary amino group (93% of diaxial conformer in CCl 4 ) leads to an IAHB OH···N stronger than in primary and tertiary amino-derivatives (53 and 54% of diaxial conformer, respectively) for 1,3-disubstituted cyclohexanes. Values obtained from the theoretical data through the B3LYP func- tional are in agreement with the experimental results and indicate that the IAHB strength that influences the conformational equilibrium of these compounds is the IAHB OH···N. Thus, the IAHB NH···O do not stabilize the diaxial conformer of the cis isomer of compounds ACNE and MCNE showing that the diequa- torial conformer will always be more stable than the diaxial conformer, independent of concentration or solvent. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Previous work on cis isomers of 3-X-cyclohexanols (X = Cl, Br, I, CH 3 ) and 3-X-1-methoxycyclohexanes (X = F, Cl, Br, I, CH 3 ) has shown that their conformational equilibria are neither controlled by conformer dipole moments nor by solvent polarity [1], but mostly by the classical syn-1,3-diaxial steric effects. However, the presence of some substituents in the six-membered ring has shown that is possible to favour the diaxial conformer through intramolec- ular hydrogen bonding (IAHB). For example, it was shown that if OH groups, of a dihydroxy compound, are sufficiently close to each other, they may form an intramolecular hydrogen bond [2]. ∗ Corresponding author. Tel.: +55 19 3521 3150; fax: +55 19 3521 3023. E-mail address: rittner@iqm.unicamp.br (R. Rittner). Abraham et al. [3] have also demonstrated, through 1 H NMR and theoretical data, that the strong OH···F hydrogen bond in trans-2- fluorocyclohexanol is responsible for the predominance of its eq–eq conformer. Recently, the occurrences of IAHB in cis-3-methoxy- [4], cis-3-ethoxy- [5] and cis-3-N,N-dimethylamino-cyclohexanols [6], which stabilize the diaxial conformer and suppress the 1,3-diaxial steric interactions, have been reported. Oliveira and Rittner emphasized the importance of IAHB on 1,3- diaxial interactions of cis-3-alkoxycyclohexanols. They established that the strength of IAHB increases with the increasing size and with the inductive effect of the cis-3-alkoxy substituent [7]. The importance of hydrogen bonding is well known, since it determines the three-dimensional structures adopted by proteins and nucleic acids, like in DNA and RNA structures where the double helixes are formed due to the presence of hydrogen bonds between the strands [8–11]. The strength of a H-bond strongly depends on both 1386-1425/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.saa.2011.02.010