Chapter 1. Stereoisomerism
• symmetry elements
symmetry planes, symmetry axes, inversion centers
Little Eliel
“Symmetry”
p. 45-58
• point groups
chiral point groups
• enantiomers and diastereomers
in chiral point groups:
chiral centers
chiral axes
planes of chirality
• notation:
Fischer D,L
Cahn, Ingold, Prelog R,S
• resolution of a racemic mixture and its detection
For symmetry, also check out http://www.reciprocalnet.org/edumodules/symmetry,
a very nice site.
…
4. Racemates (racemic mixtures)
- 1:1 mixture of enantiomers
I. Detection
Optical activity
- a chiral compound is optically active
- it rotates the plane of linearly polarized light in a polarimeter
andromeda.rutgers.edu/~huskey/335_lec.html
- linearly polarized light is a linear combination of two waves:
left + right circularly polarized light:
- experience a different refraction index in the chiral sample
(“diastereomeric interactions”)
- slow down in the sample to a different extent
?
- “circular birefringence”
Polarized light
linearly polarized wave
a) in phase
two linearly polarized waves:
b) out of phase
Polarized light continued
This is what happens to linearly polarized light in the polarimeter:
Here the right circularly polarized wave slows down in the sample.
back
4. Racemates continued
- rotation of the plane of linearly polarized light in a polarimeter:
clockwise: +α
for either R or S: (R)-(+)-… or (S)-(+)-…
anticlockwise: -α
for either R or S: (R)-(-)-… or (S)-(-)-…
- racemic mixture is given as (±)
- optical activity establishes the non-racemic character of a sample
- magnitude of the rotation α is normalized as “specific rotation” [α]
Biot’s law:
α = [α ]Tλ cl
[α] = f(T)
O
H
Ph
[α ]21D = +167
[α ]25D = +162
[α] in deg cm2 g-1
f(c)
λ is usually 589 nm (Na D-line)
T in °C
solvent needs to be listed
www.youngscientists.co.uk/node/95
[α ]21D = +182 (c = 46 g/100mL in benzene)
[α ]21D = +215 (c = 1.5 g/100mL in benzene)
- racemic mixture or meso-compound: no optical activity!
?
4. Racemates continued
- quantitative treatments of the optical activity (non-racemic character):
A. Optical purity, P
[α ]
P=
[α ]max
observed
P = +1 or -1 pure enantiomer
for the pure enantiomer
P=0
- possible problems:
racemic mixture
change in T, c, solvent
crypto-chirality
accidental degeneracy
B. Enantiomeric excess, %ee
[
R ] − [S ]
%ee =
100
[R ] + [S ]
, where [R] > [S]
- non-racemic 80:20 mixture of enantiomers ⇒ 60% ee
- the “diastereomeric excess”, %de, is defined similarly
: excess over
racemic mixture
Insert
4. Racemates continued
I. Detection
- other methods can be used to detect racemic mixtures (IR, NMR…)
- sometimes a modification step is needed: diastereomeric mixtures
(will look at this in more detail later)
1H
NMR
O
Ph
NH2
+
Ph
Cl
R,S
CH3O
O
Ph R NH
CH3O
singlet
H
R
- HCl
O
Ph
H
R
singlet
+
Ph S NH
CH3O
singlet
Ph
H
R
singlet
II. Resolution (closely linked to detection!)
Jacobus, Raban, J. Chem. Ed. 46, 351 (1969)