76
STEREOCHEMISTRY
Optical activity is the ability of a compound to
rotate the plane of polarized light. This property
arises from an interaction of the electromagnetic
radiation of polarized light with the unsymmetric
electric fields generated by the electrons in a chiral
molecule. The rotation observed will clearly depend
on the number of molecules exerting their effect, i.e.
it depends upon the concentration. Observed rotations
are thus converted into specific rotations that are
a characteristic of the compound according to the
formula below.
[a] D (solvent) =
t
a
l c
specific
rotation
observed rotation
(degrees)
length of sample tube
(decimetres)
concentration
(g ml −1 )
temperature
wavelength of
monochromatic light
D = Na 'D' line 589 nm
solvent used must be quoted:
rotation is solvent dependent
The observed rotation in degrees is divided by the
sample concentration (g ml
−1 ) and the sample tube
length (decimetres). The unusual units used transform
the measured small rotations into more manageable
numbers. The specific rotation is then usually in
the range 0–1000
◦ ; the degree units are strictly
incorrect, but are used for convenience. The polarized
light must be monochromatic, and for convenience
and consistency the D line (589 nm) in the sodium
spectrum is routinely employed. Both the temperature
and solvent may influence the rotation somewhat, so
must be stated.
Enantiomers have equal and opposite rotations.
The (+)- or dextrorotatory enantiomer is the one
that rotates the plane of polarization clockwise (as
determined when facing the beam), and the (−)- or
laevorotatory enantiomer is the one that rotates the
plane anticlockwise. In older publications, d and l
were used as abbreviations for dextrorotatory and
laevorotatory respectively, but these are not now
employed, thus avoiding any possible confusion with
D and L (see Section 3.4.10).
An equimolar mixture of enantiomers is optically
inactive, since the individual effects from the two
types of molecule are cancelled out. This mixture is
called a racemic mixture or racemate, and can be
referred to as the (±)-form. A mixture of enantiomers
in unequal proportions has a rotation numerically
less than that of either enantiomer; this measurement
could be used to determine the proportions of
each (see Box 3.6). Note that it is not possible to
predict the sign or magnitude of the optical activity
for a particular enantiomer; it must be measured
experimentally. The presence of more than one chiral
centre in a molecule results in an optical rotation that
reflects a contribution from each centre, though this
is unlikely to be a simple summation. It must also
be appreciated that a positive contribution from one
centre may be reduced, countered, or cancelled out by
a negative contribution arising from another centre or
centres (see Section 3.4.5).
Box 3.6
Optical purity and enantiomeric excess
A racemic mixture contains equal amounts of the
two enantiomeric forms of the compound and has an
optical rotation of zero: the optical rotations arising
from each of the two types of molecule are cancelled
out. It follows that a mixture of enantiomers in
unequal proportions will have a rotation that is
numerically less than that of an enantiomer. Here,
we see how to use the measured optical activity
to determine the proportions of each enantiomer in
the mixture, and therefore its optical purity. Optical
purity is a measure of the excess of one enantiomer
over the other in a sample of a compound.
There are a number of occasions when optical
purity is of interest. We shall see later that many
drugs are chiral compounds, and that biological activity often resides in just one enantiomer (see Box 3.7).
To minimize potential side effects, it is desirable to
supply the drug in a single enantiomeric form. This
might be achieved by devising a synthetic procedure
that produces a single enantiomer, an enantiospecific
synthesis. However, syntheses that are enantiospecific can be difficult to achieve, and it is more likely
that the procedure is only enantioselective, i.e. it
produces both enantiomers but with one predominating. Alternatively, it is possible to separate the
racemic mixture into the two enantiomers (resolution; see Section 3.4.8). This might not be achieved
in a single step. In both cases, it is usually necessary
to monitor just how much of the desired enantiomer
is present in the product mixture.
To illustrate the calculation of optical purity,
we shall consider another type of reaction of
interest, racemization. This is the conversion of
STEREOCHEMISTRY
Optical activity is the ability of a compound to
rotate the plane of polarized light. This property
arises from an interaction of the electromagnetic
radiation of polarized light with the unsymmetric
electric fields generated by the electrons in a chiral
molecule. The rotation observed will clearly depend
on the number of molecules exerting their effect, i.e.
it depends upon the concentration. Observed rotations
are thus converted into specific rotations that are
a characteristic of the compound according to the
formula below.
[a] D (solvent) =
t
a
l c
specific
rotation
observed rotation
(degrees)
length of sample tube
(decimetres)
concentration
(g ml −1 )
temperature
wavelength of
monochromatic light
D = Na 'D' line 589 nm
solvent used must be quoted:
rotation is solvent dependent
The observed rotation in degrees is divided by the
sample concentration (g ml
−1 ) and the sample tube
length (decimetres). The unusual units used transform
the measured small rotations into more manageable
numbers. The specific rotation is then usually in
the range 0–1000
◦ ; the degree units are strictly
incorrect, but are used for convenience. The polarized
light must be monochromatic, and for convenience
and consistency the D line (589 nm) in the sodium
spectrum is routinely employed. Both the temperature
and solvent may influence the rotation somewhat, so
must be stated.
Enantiomers have equal and opposite rotations.
The (+)- or dextrorotatory enantiomer is the one
that rotates the plane of polarization clockwise (as
determined when facing the beam), and the (−)- or
laevorotatory enantiomer is the one that rotates the
plane anticlockwise. In older publications, d and l
were used as abbreviations for dextrorotatory and
laevorotatory respectively, but these are not now
employed, thus avoiding any possible confusion with
D and L (see Section 3.4.10).
An equimolar mixture of enantiomers is optically
inactive, since the individual effects from the two
types of molecule are cancelled out. This mixture is
called a racemic mixture or racemate, and can be
referred to as the (±)-form. A mixture of enantiomers
in unequal proportions has a rotation numerically
less than that of either enantiomer; this measurement
could be used to determine the proportions of
each (see Box 3.6). Note that it is not possible to
predict the sign or magnitude of the optical activity
for a particular enantiomer; it must be measured
experimentally. The presence of more than one chiral
centre in a molecule results in an optical rotation that
reflects a contribution from each centre, though this
is unlikely to be a simple summation. It must also
be appreciated that a positive contribution from one
centre may be reduced, countered, or cancelled out by
a negative contribution arising from another centre or
centres (see Section 3.4.5).
Box 3.6
Optical purity and enantiomeric excess
A racemic mixture contains equal amounts of the
two enantiomeric forms of the compound and has an
optical rotation of zero: the optical rotations arising
from each of the two types of molecule are cancelled
out. It follows that a mixture of enantiomers in
unequal proportions will have a rotation that is
numerically less than that of an enantiomer. Here,
we see how to use the measured optical activity
to determine the proportions of each enantiomer in
the mixture, and therefore its optical purity. Optical
purity is a measure of the excess of one enantiomer
over the other in a sample of a compound.
There are a number of occasions when optical
purity is of interest. We shall see later that many
drugs are chiral compounds, and that biological activity often resides in just one enantiomer (see Box 3.7).
To minimize potential side effects, it is desirable to
supply the drug in a single enantiomeric form. This
might be achieved by devising a synthetic procedure
that produces a single enantiomer, an enantiospecific
synthesis. However, syntheses that are enantiospecific can be difficult to achieve, and it is more likely
that the procedure is only enantioselective, i.e. it
produces both enantiomers but with one predominating. Alternatively, it is possible to separate the
racemic mixture into the two enantiomers (resolution; see Section 3.4.8). This might not be achieved
in a single step. In both cases, it is usually necessary
to monitor just how much of the desired enantiomer
is present in the product mixture.
To illustrate the calculation of optical purity,
we shall consider another type of reaction of
interest, racemization. This is the conversion of