Transcript Optical Activity

Optical Activity
 Enantiomers are different compounds:
 Same boiling point, melting point, density
 Same refractive index
 Rotate plane polarized light in opposite
directions (polarimetry)
 Different interaction with other chiral
molecules
 Enzymes
 Taste buds, scent
Optical Activity
 Polarimetry is a laboratory technique that
measures the interaction between a compound
and plane polarized light.
 Since enantiomers interact with plane polarized
light differently, polarimetry can be used to
distinquish between enantiomers.
Optical Activity
 “Regular” (unpolarized) light vibrates in all
directions.
 Plane-polarized light:
 light composed of waves that vibrate in only
a single plane
 obtained by passing unpolarized light through
a polarizing filter
Optical Activity
 When plane polarized light passes through a
solution containing a single chiral compound,
the chiral compound causes the plane of
vibration to rotate.
 Polarimeter
Optical Activity
 Chiral compounds are optically active:
 capable of rotating the plane of polarized
light
 Enantiomers rotate the plane of polarized light
by exactly the same amount but in opposite
directions.
CH3
CH3
C
C
H
CH2CH3
HO
(S)-2-butanol
+13.5o rotation
CH3CH2
H
OH
(R)-2-butanol
CH3
o
-13.5 rotation
Optical Activity
 Compounds that rotate the plane of polarized
light to the right (clockwise) are called
dextrorotatory.
d
 (+)
IUPAC convention
 Compounds that rotate the plane of polarized
light to the left (counterclockwise) are called
levorotatory.
l
 (-)
IUPAC convention
Optical Activity
CH3
CH3
C
C
H
CH2CH3
HO
+13.5o rotation
(+)-2-butanol
H
OH
o
-13.5 rotation
(-)-2-butanol
CH3
(S)-(+)-2-butanol
(R)-(-)-2-butanol
C
H
CH2CH3
 The direction and magnitude of rotation
HO must
CH3CH2
be determined experimentally.
 There is NO CORRELATION between (R)
and (S) configuration and the direction of
rotation.
2
2
I
I
Optical Activity
H2N
I
I
H
C
HO
CO2H
CH2
O
(S)-(-)-thyroxine
biologically active
I
I
I
I
H
NH2
C
HO
CH2
O
CO2H
I
I
(R)-(+)thyroxine
inactive
Unlike (R)-(-)-2-butanol, (R)-thyroxine rotates
light to the right.
I
I
H2N
H
Optical Activity
 The angular rotation observed in a polarimeter
depends on:
 the optical activity of the compound
 the concentration of the sample
 the path length of the sample cell
 A compound’s specific rotation [a] can be used
as a characteristic physical property of a
compound:
 the rotation observed using a 10-cm sample
cell and a concentration of 1 g/mL.
Optical Activity
[a ] 
a (observed )
c l
where a = specific rotation
c = concentration in g/mL
l = path length in dm
a (observed) = rotation observed for a
specific sample
Optical Activity
Example: A solution of 2.0 g of (+)glyceraldehyde in 10.0 mL of water was placed in
a 100. mm polarimeter tube. Using the sodium
D line, a rotation of 1.74o was observed at
25oC. Calculate the specific rotation of (+)glyceraldehyde.
[a ] 
a (observed )
c l
Optical Activity
Given: a (obs) = 1.74o
1m
10 dm
l  100. mm 

 1.00 dm
1000 mm 1 m
2.0 g
c
 0.20 g mL
10.0 ml
Find: [a]
 1.74
o
[a ] 
 8.7
0.20 1.00
Optical Activity
H
HO
CH3
CH3
C
C
CH2CH3
CH3CH2
H
OH
+13.5o rotation
-13.5o rotation
(S)-(+)-2-butanol
CH3
(R)-(-)-2-butanol
 A mixture containing equal amounts of C
(+)-2-
butanol and (-)-2-butanol gives an Hobserved
CH2CH3
HO
rotation of zero degrees
 Just like an achiral molecule
Optical Activity
 A solution containing equal amounts of two
enantiomers is called a racemic mixture.
 Racemate
 (+) pair
 (dl) pair
 Racemic mixtures are optically inactive.
 Racemic mixtures are designated using the
prefix (+):
 (+)-2-butanol
Optical Activity
 Racemic mixtures are often formed during
chemical reactions when the reactants and
catalysts used are achiral.
Optical Activity
 Some mixtures are neither optically pure (all
one enantiomer) nor racemic (equal mixture of
both enantiomers).
 Optical purity:
 Ratio of the rotation of a mixture to the
rotation of a pure enantiomer
 o.p. =
observed rotation
x 100%
rotation of pure enantiomer
Optical Activity
Example: (-)-2-butanol has a specific rotation
of - 13.5o while the specific rotation of (+)-2butanol is +13.5o. A mixture containing (+) and
(-)-2-butanol has an observed rotation of –
8.55o. Does the mixture contain more (+) or
more (-)-2-butanol? Calculate the optical purity
of the mixture.
Optical Activity
 Another method to express (or determine) the
relative amounts of enantiomers present in a
mixture is enantiomeric excess.
 Numerically identical to optical purity
e.e. = o.p. = excess of one over the other x 100%
entire mixture
e.e. 
d l
d l
x 100%
Optical Activity
Example: Calculate the e.e of a mixture
containing 25% (+)-2-butanol and 75% (-)-2butanol.
Optical Activity
Example: Calculate the relative proportions of
(+)-2-butanol and (-)-2-butanol required to give
an observed rotation of +0.45o if the specific
rotation of (+)-2-butanol is 13.5o.
Optical Activity
 Any (or all) of a set of diastereomers may be
O
optically active (if it has a non-superimposable
C H
mirror image)
 Pairs of
light by
O
H
OH
HO
H
H
OH rotate
optically active diastereomers
H
OH
different amounts.
CH2OH
O
C
C
H
HO
H
H
O
H
OH
H
OH
OH
CH2OH
(+)-glucose
+ 52.5o
H
HO
HO
H
H
OH
H
H
OH
CH2OH
(+)-galactose
+ 83.9o
Separation of Stereoisomers &
Structural Isomers
 Structural isomers and diastereomers have
different physical properties:
 BP, MP, density, refractive index, solubility
 Can be separated through conventional
means (distillation, recrystallization,
chromatography)
CO2H CO2H CO2H CO2H
BrH
Br
H
BrH
BrH
Br
Br H Br HH
BrH
CO2H CO2H Co2H CO2H
MP = 158oC
MP = 256oC
Resolution of Enantiomers
 Since enantiomers have identical physical
properties, they cannot be separated by
conventional methods.
 Distillation and recrystallization fail.
 The process of separating enantiomers is called
resolution.
 Two methods:
 chemical resolution
 chromatographic resolution
Resolution of Enantiomers
 Chemical resolution of enantiomers:
 temporarily convert both enantiomers into
diastereomers
 react with an enantiomerically pure
(natural) product
 separate the diastereomers based on
differences in physical properties
 convert each diastereomer back into the
original enantiomer
Resolution of Enantiomers
Resolution of Enantiomers
 Chromatographic resolution of enantiomers:
 Prepare column containing stationary phase
coated with a chiral compound
 Enantiomers form diastereomeric complexes
with the chiral stationary phase
 Separate the diastereomeric complexes
based on differences in affinity for
stationary phase
 strongly complexed: elutes slowly
 weakly complexed: elutes more quickly
Chiral Compounds w/o Asymmetric Atoms
 Although most chiral compounds have at least
one asymmetric atom, there are some chiral
compounds that have zero asymmetric atoms:
 conformation enantiomers
 allenes
Chiral Compounds w/o Asymmetric
Atoms
 Conformational enantiomers:
 compounds that are so bulky or so highly
strained that they cannot easily confert
from one chiral conformation to the mirrorimage conformation
 “locked” into one conformation
Chiral Compounds w/o Asymmetric Atoms
 Allenes:
 compounds containing a C=C=C unit
 central carbon is sp hybridized
– linear