Conformational Analysis of 9,18-Difluoro-2,11-diaza[3.3]metacyclophane

Abstract

The conformational isomers (syn and anti) of 9,18-difluoro-2,11-diaza[3.3]metacyclophane, 1, were isolated at ambient temperature and each was identified by 19F NMR spectra. The anti isomer gradually converted to the syn isomer in solution, and kinetic measurements of this conversion afforded the Arrhenius activation energy, E a = 24.8 ± 0.9 kcal/mol, in acetonitrile. The difference in thermodynamic stability of the syn and anti isomers in DMSO was estimated to be ca. 2 kcal/mol (298 K) on the basis of the variable temperature NMR method. The three conformational isomers, boat−boat, chair−boat, and chair−chair, are present in the syn isomer in solution. The relative stability order of the three isomers, boat−boat, chair−boat, chair−chair, is estimated by the 1H- and 19F NMR spectra. The boat−boat isomer is predominant at low temperatures, but the ratio of the other two isomers, chair−boat and chair−chair, is gradually increased as the temperature is raised.

9‐Fluoro‐18‐hydroxy‐[3.3]metacyclophane: Synthesis and Estimation of a C−F···H−O Hydrogen Bond

“…As shown in Figure 3, the OH proton spectra of 1 and 2 are strongly temperature-dependent, especially below 240 K. In the case of 2, two kinds of OH proton signals appeared below 243 K. At this temperature, conformational changes of the trimethylene bridge (boat Ǟ ǟ chair) are involved. [25] Therefore, the two OH protons correspond to those of the conformational isomers. In the case of cyclophane 1, conformational changes also occur below 243 K. However, only one kind of OH proton The difference of chemical shift of the OH proton, ∆δ, between 1 and 2 is almost constant (∆δ ഠ 0.5 ppm in [D 14 ]methylcyclohexane) between 273 and 363 K, and the ∆δ value indicates the C-F···HϪO binding energy.…”

Quantitative Four‐State Conformational Analysis by Ring Current NMR Anisotropy: A Family of Molecules Capable of Intramolecular π‐Stacking

“…[19,20] Also pertinent to this work is a three-state conformational distribution reported for a cyclophane using 19 F, 13 C and 1 H NMR spectrometry. [21] Derivatives of molecules 1Ϫ3 are interesting because they have served as models for intramolecular π-stacking.…”