CHAPTER 7

CHIROPTICAL METHODS FOR

DETERMINATION OF ORGANIC
STRUCTURES

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 Types of polarized light
• Plane polarized light consists two circularly polarized
components of equal intensity
• Two circularly polarized components are like left- and
right-handed springs
• As observed by looking at the source, right-handed
circularly polarized light rotates clockwise
• Frequency of rotation is related to the frequency of the
light
• Can be resolved into its two circularly polarized
components
• When added together after passing through an optically
isotropic medium, plane polarized light results

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 Circular Dichroism
Circular dichroism (CD) spectroscopy measures
differences in the absorption of left-handed polarized
light versus right-handed polarized light which arise due
to structural asymmetry. The absence of regular structure
results in zero CD intensity, while an ordered structure
results in a spectrum which can contain both positive and
negative signals.

Jasco J-810 Circular Dichroism System

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Chiral structure can be distinguished and
characterized by polarized light

Optical rotation:
rotation the rotation of linearly polarized light by
the sample
Optical rotary dispersion:
dispersion the variation of optical
rotation as a function of wavelength. The spectrum of optical
rotation.
Circular Dichroism:
Dichroism the difference in absorption of left and
right circularly light.

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 Cotton Effect
•Positive Cotton effect is where the
peak is at a higher wavelength than the
trough
•Negative Cotton effect is the opposite
•Optically pure enantiomers always
display opposite Cotton effect ORD
curves of identical magnitude
•Zero crossover point between the peak
and the trough closely corresponds to
the normal UV max

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 Circular Dichroism
The difference between the absorption of
left and right handed circularly-polarised
light and is measured as a function of
wavelength. CD is measured as a quantity
called mean residue ellipticity, whose
units are degrees-cm2/dmol.

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 ORD and CD
• CD plots are Gaussian rather than S-shaped.
• Positive or negative deflections depend on the sign of
 or [] and corresponds to the sign of the Cotton
effect
• Maximum of the CD occurs at the absorption max
• Where more than one overlapping Cotton effect, the
CD may be easier to interpret than the ORD with
overlapping S-shaped bands

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ORD spectra are dispersive (called a Cotton effect
for a single band) whereas circular dichroism
spectra are absorptive. The two phenomena are
related by the so-called König-Kramers
transforms. 11
 Other Uses of CD – Absolute
Stereochemistry of Chromophores

Organic conformational analysis and stereochemistry from circular dichroism spectroscopy,

Lightner and Gurst, Wiley, 2000.
 Application of CD to Structure
Determination
• The most important aspect of a CD curve is
the sign of the Cotton Effect. Apart from
numerous assessments of the sign and
magnitude of the Cotton Effect for particular
chromophores, using mostly MO-based
theory, many applications use one of many
semiempirical rules: sector rules for achiral
chromophores and helicity rules for chiral
chromophores. These are summarized below.
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 The Axial Haloketone Rule and the Octant Rule for Saturated Ketones

• The octant rule is the most widely applied sector

rule. It was developed from an earlier rule,
known as the “axial haloketone rule”, based on
ORD measurements carried out on steroidal
ketones that had been (axially) substituted with a
halogen atom at the -carbon. Axial substitution
(conformation) is often preferred because of the
dipole-dipole repulsions in the equatorial isomer:

• O O

Cl
ax eq
Cl

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• The position of the halogen was observed to influence the sign of
the Cotton Effect and similar effects were found for other
substituents, such as NR2, SR, SO2R, etc.
• It was suggested that prediction of the sign of the Cotton Effect is
possible if the ketone group is viewed along the O=C bond in the
direction of the ring with the carbonyl carbon at the head of the
chair (the major conformer in cyclohexane ring systems). If the
axial –halogen is found on the right (as in the (S)-enantiomer),
then there exists a positive Cotton Effect; if it appears on the left,
a negative Cotton effect is observed, as shown below.

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 Determination of Position of Halogen Substitution
(Constitution)

• In the example below, a negative Cotton Effect is seen upon bromination

of the cyclic fused ring ketone. Therefore, substitution must have
occurred predominantly at the 5 position.

CH3
CH3 C8H17
HO2C
5 7
HO2C
O
H H

Br Br
Substitution by Br gives
-CE at 5 and +CE at 7

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 Determination of Absolute Configuration

• The configuration of the 11-bromo-12-ketosteroid product from the

bromination of the parent 12-ketosteroid was deduced to be (R) from the
observation of a negative Cotton Effect.

O
CH3
Br CO2CH3

CH3 11

AcO

11--Br (equatorial) gives +CE (as in the parent ketone)

11--Br (axial) gives -CE

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 Demonstration of conformational mobility

• On chlorination of (R)-(+)-3-methylcyclohexanone, a crystalline 2-chloro-5-

methyl product is isolated that shows a negative Cotton Effect in octane,
but a positive one in methanol. The negative CE is consistent only with
trans stereochemistry, with independent evidence for axial Cl (in octane).

 The change in sign of the CE on changing the solvent to (more polar)

methanol is Presumably a reflection of the greater stability of the
equatorial conformer in that solvent.
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Examples of CD and ORD spectrum for determination of Absolute stereochemistry

Beilstein J. Org. Chem. 2014, 10, 276–281. 21

 Example: Circular Dichroism of ß-lactams

The investigated (6R,7S)-7-((1R)-1-hydroxyethyl)-8oxo-1-aza-bicyclo[4.2.0]octane.

WIREs Comput Mol Sci 2012, 2:150-66
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