Laboratory of Organic Synthesis and Natural Products, Department of Chemistry and Biology, Federal University of Technology-Paraná, Curitiba, PR, Brazil.
Spectrochim Acta A Mol Biomol Spectrosc. 2011 May;78(5):1599-605. doi: 10.1016/j.saa.2011.02.010. Epub 2011 Feb 13.
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% (ΔG(eqeq-axax)=0.06 kcal mol(-1)) in CCl(4) to 93% (ΔG(eqeq-axax)=-1.53 kcal mol(-1)) in DMSO, while for MCOL it goes from 7% (ΔG(eqeq-axax)=1.54 kcal mol(-1)) in CCl(4) to 82% (ΔG(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 equilibrium 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. Moreover, 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 functional 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 diequatorial conformer will always be more stable than the diaxial conformer, independent of concentration or solvent.
（1）H NMR 数据分析表明，顺式-3-氨基环已醇（ACOL）的浓度效应使其在丙酮-d（6）中的非对映异构体从 0.01 mol/L 时的 60%增加到 0.40 mol/L 时的 70%。类似的增加也观察到顺式-3-N-甲基氨基环已醇（MCOL）的非对映异构体，从 CDCl（3）0.01 mol/L 时的 32%增加到 CDCl（3）0.40 mol/L 时的 55%。溶剂碱性的增加也导致这两种化合物的非对映异构体的稳定效应较大。对于 ACOL，它从 CCl（4）中的 47%（ΔG（eqeq-axax）=0.06 kcal/mol）增加到 DMSO 中的 93%（ΔG（eqeq-axax）=-1.53 kcal/mol），而对于 MCOL，它从 CCl（4）中的 7%（ΔG（eqeq-axax）=1.54 kcal/mol）增加到吡啶-d（6）中的 82%（ΔG（eqeq-axax）=-0.88 kcal/mol）。这些结果表明，分子内氢键（IAHB）OH⋯N 和 NH⋯O 稳定了这些化合物在非极性溶剂中的轴向构象。对于顺式-3-氨基-1-甲氧基环已烷（ACNE）和顺式-3-N-甲基氨基-1-甲氧基环已烷（MCNE），随着溶剂极性的变化，平衡没有发生变化。这些结果首次表明，IAHB NH⋯O 不足以稳定这些化合物的轴向构象，并且 ACOL 和 MCOL 的顺式异构体的构象平衡仅受 IAHB OH⋯N 的影响。此外，仲氨基（CCl（4）中 93%的轴向构象）的存在导致 1,3-取代环己烷中 IAHB OH⋯N 比伯和叔氨基衍生物（分别为 53%和 54%的轴向构象）更强。通过 B3LYP 函数获得的理论数据与实验结果一致，表明影响这些化合物构象平衡的 IAHB 强度是 IAHB OH⋯N。因此，IAHB NH⋯O 不能稳定 ACNE 和 MCNE 的顺式异构体的轴向构象，表明非对映异构体将始终比轴向构象更稳定，而与浓度或溶剂无关。
