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 EnzymesTaste 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.

C

CH3

CH2CH3H

HO

C

C

CH3

CH2CH3H

HO

HOH

CH3

CH3CH2

(S)-2-butanol (R)-2-butanol

+13.5o rotation -13.5o 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

The direction and magnitude of rotation must be determined experimentally. There is NO CORRELATION between (R)

and (S) configuration and the direction of rotation.

C

CH3

CH2CH3H

HO

C

C

CH3

CH2CH3H

HO

HOH

CH3

CH3CH2

(+)-2-butanol (-)-2-butanol

+13.5o rotation -13.5o rotation

(S)-(+)-2-butanol (R)-(-)-2-butanol

Optical Activity

(S)-(-)-thyroxinebiologically activeO CH2

CCO

2H

HH2NI I

II

HO

O CH2HO

I

I I

IC

CO2H

NH2

H

(R)-(+)-thyroxineinactive

O CH2

CCO

2H

HH2NI I

II

HO

O CH2HO

I

I I

IC

CO2H

NH2

H

Unlike (R)-(-)-2-butanol, (R)-thyroxine rotates light to the right.

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 [] 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

lc

observed

)(][

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.

lc

observed

)(][

Optical Activity

dmm

dm

mm

mmml 00.1

1

10

1000

1.100

mLgml

gc 20.0

0.10

0.2

Given: (obs) = 1.74o

o7.800.120.0

74.1][

Find: []

Optical Activity

A mixture containing equal amounts of (+)-2-butanol and (-)-2-butanol gives an observed rotation of zero degrees Just like an achiral molecule

C

CH3

CH2CH3H

HO

C

C

CH3

CH2CH3H

HO

HOH

CH3

CH3CH2

+13.5o rotation -13.5o rotation

(S)-(+)-2-butanol (R)-(-)-2-butanol

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 (+)-2-butanol 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

%100.. xld

ldee

Optical Activity

Example: Calculate the e.e of a mixture containing 25% (+)-2-butanol and 75% (-)-2-butanol.

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 optically active (if it has a non-superimposable mirror image)

Pairs of optically active diastereomers rotate light by different amounts.

C

O

HOHHOHOH

CH2OHHH

HHO

COHHHHO

OHHCH2OH

O

H

H OH

C

O

HOHHOHOH

CH2OHHH

HHO

COHHHHO

OHHCH2OH

O

H

HHO(+)-glucose

+ 52.5o

(+)-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)

H BrCO2H

CO2HBr H

CO2H

Co2H

HH

BrBr

H BrCO2H

CO2HBr H

CO2H

CO2H

HH

BrBr

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 diastereomersreact 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 phasestrongly complexed: elutes slowlyweakly 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 mirror-image 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