Page 174 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

154 Visual models, additional information and exercises on Cyclohexane Conforma-
tions can be found in the Digital Resource available at: Springer.com/carey-
CHAPTER 2 sundberg.
Stereochemistry,
Conformation,
and Stereoselectivity Substitution on a cyclohexane ring does not greatly affect the rate of conforma-
tional inversion, but does change the equilibrium distribution between alternative chair
forms. All substituents that are axial in one chair conformation become equatorial
on ring inversion, and vice versa. For methylcyclohexane, G for the equilibrium
is −1 8kcal/mol, corresponding to a composition with 95% of the equatorial methyl
conformation.

CH 3
CH 3

Two factors contribute to the preference for the equatorial conformation. The
equatorial methyl conformation corresponds to an anti arrangement with respect
to the C(2)–C(3) and C(6)–C(5) bonds, whereas the axial methyl group is in a
gauche relationship to these bonds. We saw earlier that the gauche conformation
of n-butane is 0.5–0.6 kcal/mol higher in energy than the anti conformation. In
addition, there is a van der Waals repulsion between the axial methyl group and
the axial hydrogens at C(3) and C(5). Interactions of this type are called 1,3-diaxial
interactions.

H CH 3
H
CH 3
gauche-butane relationships anti-butane relationships
in axial methylcyclohexane in equatorial methylcyclohexane

Energy differences between conformations of substituted cyclohexanes can be
measured by several methods, as can the kinetics of the ring inversion processes. NMR
spectroscopy is especially valuable for both thermodynamic and kinetic studies. 51
Depending on the rate of the process, the difference in chemical shift between the two
sites and the field strength of the spectrometer, the observed spectrum will be either
−1
5
a weighted average spectrum (rapid site exchange, k> 10 sec ) or a superposition
of the spectra of the two conformers reflecting the equilibrium composition (slow
−1
3
site exchange, k< 10 sec ). At intermediate rates of exchange, broadened spectra
are observed. Analysis of the temperature dependence of the spectra can provide the
activation parameters for the conformational process. Figure 2.14 illustrates the change
in appearance of a simple spectrum.
For substituted cyclohexanes, the slow-exchange condition is met at tempera-

tures below about −50 C. Data for the half-life for conformational equilibration of
51
G. Binsch, Top. Stereochem. 3, 97 (1968); F. G. Riddell, Nucl. Magn. Reson., 12, 246 (1983);
J. Sandstrom, Dynamic NMR Spectroscopy, Academic Press, New York, 1982; J. L. Marshall, Nuclear
Magnetic Resonance, Verlag Chemie, Deerfield Beach, FL, 1983; M. Oki, Applications of Dynamic NMR
to Organic Chemistry, VCH Publishers, Deerfield Beach, FL, 1985; Y. Takeuchi and A. P. Marchand,
eds., Applications of NMR Spectroscopy in Stereochemistry and Conformational Analysis, VCH
Publishers, Deerfield Beach, FL, 1986.