CONFIGURATIONAL ISOMERS
77
a single enantiomer into a racemic mixture of the
two enantiomers. It depends upon the chemical
nature of the compound whether this is easily
achievable (see Sections 10.1.2 and 10.8). One
compound that racemizes readily is hyoscyamine,
a natural alkaloid found in deadly nightshade,
which is used as an anticholinergic drug (see
Box 3.7). The natural compound is laevorotatory,
[α]
20
D − 21
◦ (EtOH), and the enantiomer is almost
devoid of biological activity.
Upon heating with dilute base such as 1%
NaOH for about an hour, hyoscyamine racemizes, and the solution becomes optically inactive
(see Box 10.9). At shorter times, racemization is
incomplete and the solution will still be optically
active. Consider first a very simple situation in
which exactly half of the material has racemized.
Half of the material is now optically inactive,
consisting of equal amounts of each enantiomer,
whilst the other half is still unchanged. Since
the concentration of the unchanged part is half
of the original concentration, the optical rotation
will also have dropped to half its original value.
The solution will contain 50% laevorotatory isomer and 50% racemate. However, the racemate is
itself a 50 : 50 mixture of the two enantiomers, so
the solution actually contains 25% dextrorotatory
and 25 + 50% = 75% laevorotatory enantiomers.
Now let us consider when measurements indicate [α]
20
D − 9.2
◦ . Calculations now tell us that
The physical properties of enantiomers and racemates, except for optical rotation and melting points, are
usually the same. The melting points of (+)- and (−)enantiomers are the same, though that of the racemate is
the sample is 56.2% racemic, and contains 71.9%
laevorotatory enantiomer and 28.1% dextrorotatory
enantiomer. These figures are derived as follows:
the optical purity(%)
=
specific rotation of sample
specific rotation of pure enantiomer
× 100
= −9.2
◦ / − 21
◦ × 100 = 43.8%
The sample thus contains 43.8% of laevorotatory
enantiomer and 100 − 43.8% = 56.2% of racemate,
the latter contributing no overall optical activity. The
racemate contains equal amounts of laevorotatory
and dextrorotatory enantiomers, i.e. it contributes
28.1% of each isomer to the overall mixture. Therefore, we have 43.8 + 28.1 = 71.9% of laevorotatory
enantiomer, and 28.1% of dextrorotatory enantiomer
in the partially racemized mixture.
Many workers use the equivalent term percentage
enantiomeric excess rather than optical purity:
% Enantiomeric excess
=
moles of one enantiomer−
moles of other enantiomer
total moles of both enantiomers
× 100
but this is exactly equivalent to optical purity.
From the above calculations, one can see that the
laevorotatory enantiomer (71.9%) is in excess of the
dextrorotatory enantiomer (28.1%) by 43.8%.
Box 3.7
Pharmacological properties of enantiomers
Although most physical properties of enantiomers are identical, pharmacological properties may be different.
There are examples of compounds where:
• only one enantiomer is active;
• both enantiomers show essentially identical activities;
• both enantiomers have similar activity, but one enantiomer is more active;
• enantiomers show different pharmacological activities.
These observations may reflect the proximity of the chiral centre to the part of the molecule that binds with the
receptor site.
77
a single enantiomer into a racemic mixture of the
two enantiomers. It depends upon the chemical
nature of the compound whether this is easily
achievable (see Sections 10.1.2 and 10.8). One
compound that racemizes readily is hyoscyamine,
a natural alkaloid found in deadly nightshade,
which is used as an anticholinergic drug (see
Box 3.7). The natural compound is laevorotatory,
[α]
20
D − 21
◦ (EtOH), and the enantiomer is almost
devoid of biological activity.
Upon heating with dilute base such as 1%
NaOH for about an hour, hyoscyamine racemizes, and the solution becomes optically inactive
(see Box 10.9). At shorter times, racemization is
incomplete and the solution will still be optically
active. Consider first a very simple situation in
which exactly half of the material has racemized.
Half of the material is now optically inactive,
consisting of equal amounts of each enantiomer,
whilst the other half is still unchanged. Since
the concentration of the unchanged part is half
of the original concentration, the optical rotation
will also have dropped to half its original value.
The solution will contain 50% laevorotatory isomer and 50% racemate. However, the racemate is
itself a 50 : 50 mixture of the two enantiomers, so
the solution actually contains 25% dextrorotatory
and 25 + 50% = 75% laevorotatory enantiomers.
Now let us consider when measurements indicate [α]
20
D − 9.2
◦ . Calculations now tell us that
The physical properties of enantiomers and racemates, except for optical rotation and melting points, are
usually the same. The melting points of (+)- and (−)enantiomers are the same, though that of the racemate is
the sample is 56.2% racemic, and contains 71.9%
laevorotatory enantiomer and 28.1% dextrorotatory
enantiomer. These figures are derived as follows:
the optical purity(%)
=
specific rotation of sample
specific rotation of pure enantiomer
× 100
= −9.2
◦ / − 21
◦ × 100 = 43.8%
The sample thus contains 43.8% of laevorotatory
enantiomer and 100 − 43.8% = 56.2% of racemate,
the latter contributing no overall optical activity. The
racemate contains equal amounts of laevorotatory
and dextrorotatory enantiomers, i.e. it contributes
28.1% of each isomer to the overall mixture. Therefore, we have 43.8 + 28.1 = 71.9% of laevorotatory
enantiomer, and 28.1% of dextrorotatory enantiomer
in the partially racemized mixture.
Many workers use the equivalent term percentage
enantiomeric excess rather than optical purity:
% Enantiomeric excess
=
moles of one enantiomer−
moles of other enantiomer
total moles of both enantiomers
× 100
but this is exactly equivalent to optical purity.
From the above calculations, one can see that the
laevorotatory enantiomer (71.9%) is in excess of the
dextrorotatory enantiomer (28.1%) by 43.8%.
Box 3.7
Pharmacological properties of enantiomers
Although most physical properties of enantiomers are identical, pharmacological properties may be different.
There are examples of compounds where:
• only one enantiomer is active;
• both enantiomers show essentially identical activities;
• both enantiomers have similar activity, but one enantiomer is more active;
• enantiomers show different pharmacological activities.
These observations may reflect the proximity of the chiral centre to the part of the molecule that binds with the
receptor site.