Page 310 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

P1: GRB Final Pages
Encyclopedia of Physical Science and Technology EN016B-738 July 31, 2001 14:0

Stereochemistry 91

conformations of which the envelope (four carbon atoms
in a plane, one out of plane) and the half-chair (three ad-
jacent carbons in a plane, the fourth above that plane and
the fifth below) are the most symmetrical. The barrier be-
tween these conformations is very low; thus their rapid
interconversion, which involves up-and-down motions of
successive adjacent carbon atoms, has the appearance of
FIGURE 14 Conformation of 3β-cholestanol.
a bulge moving around the rings; this process has there-
fore been named “pseudorotation.” Higher cycloalkanes
from C(7) on display families of conformations which
about 42 kJ/mole and interconversion of the two conform-
are separated by barriers similar to those in cyclohexane,
ers is extremely rapid at room temperature. Thus chloro-
but within a given family there may be several individual
cyclohexane (Fig. 15, X = Cl) exists in rapid equilibrium
members interconverted by pseudorotation. This subject
between axial and equatorial conformers which differ in
is discussed in detail in Eliel and Wilen (1994).
free energy by only about 25 kJ/mole, corresponding to
◦
74% of the equatorial and 26% of the axial isomer at 25 C.
As expected, in the infrared spectrum there are two C−Cl
stretch frequencies, but in the laboratory, chlorocyclohex- XIII. CHIROPTICAL PROPERTIES.
ane, even though a mixture of two conformers, appears as a ENANTIOMERIC PURITY
homogeneous substance with the average properties (such
as chemical shifts in NMR) of the two conformers. When By “chiroptical properties” are meant optical properties
◦
one cools the substance to ca. −60 C (the exact tempera- that differ between enantiomers and can be used to char-
ture required depends on the operational frequency of the acterize them. They comprise optical rotation, optical ro-
NMR instrument), however, two different NMR spectra tatory dispersion (ORD), and circular dichroism (CD).
begin to emerge, and at −150 C the equatorial conformer Optical rotation has already been discussed. Because
◦
of its critical dependence on solvent (including cosol-
has actually been crystallized from trideuteriovinyl chlo-
vents, such as ethanol in chloroform), temperature, con-
ride solution, with concomitant enrichment of the axial
centration, and the potential presence of impurities, es-
isomer in solution.
pecially chiral impurities, in the sample, experimental
Equilibria for a large number of monosubstituted cyclo-
determination of [α] requires considerable care and many
hexanes have been determined and tabulated; they were
mostly determined by low-temperature 13 C NMR spec- of the values given in the literature cannot be trusted. This
is unfortunate since it is often desirable to determine the
troscopy (Eliel and Wilen, 1994).
“enantiomeric purity” of a sample to see whether the de-
The conformations of piperidine (azacyclohexane) and
sired enantiomer is obtained free of the other. (For exam-
tetrahydropyran (oxacyclohexane) are qualitatively simi-
ple, in pharmaceutical chemistry one wants to obtain the
lar to those of cyclohexane. (Some quantitative differences
pure eutomer free of the distomer; see above.) Since in all
are seen, for example, in the equatorial preferences of
but a few cases optical rotation is proportional to the frac-
some substituents resulting from dipolar interactions with
tion of the major enantiomer in the total substance, one
the ring hetero atom and from the fact that C–N and C–O
might expect enantiomeric or optical purity to be equal to
distances are shorter than C–C in cyclohexane.) These
ring systems are important, being found in alkaloids and 100[α obs ]/[α max ]%, where [α max ] is the (presumed known)
hexose sugars, respectively. specificrotationofanenantiomericallypuresample.How-
Because of torsional (eclipsing) strain, cyclobutane and ever, this is true only if both values have been accurately
cyclopentane are not planar. Cyclobutane is wing-shaped; determined under exactly the same conditions (solvent,
cyclopentane oscillates among a number of low-energy temperature, etc.).
Because of this difficulty, other, more reliable methods
of determining enantiomeric purity (now no longer called
“optical purity”) have been developed. Basically these de-
pend on converting the enantiomers into diastereomers,
either by covalent chemical bonding or by complexing
in some fashion, with another, usually enantiomerically
pure chiral auxiliary. (For some methods the auxiliary
FIGURE 15 Conformational inversion of substituted cyclohex-
ane. [Reprinted with permission from Eliel, E. L., and Wilen, need not even be enantiomerically pure.) Once the enan-
S. H. (1994). “Stereochemistry of Organic Compounds,” Wiley, tiomers have been converted into diastereomers, their ratio
New York.] can be determined by NMR or chromatographic methods,