STK 1233

Organic Chemistry 1
(Group 3)

LU 4.0:
Stereochemistry: Chiral Molecules

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INTRODUCTION – THE CONCEPT
 ISOMERISM deals with compounds having the same molecular
formula.

 Compounds with different chemical and/or physical properties but

having the same molecular formula are isomers (or isomeric) to each
other.

 Type of isomers ;-

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 sometimes called Structural Isomers
 molecules having the same molecular formula but differ from each other
in the sequence their atoms are joined together (connectivity).
connectivity

 The different types of structural isomers:

1. Chain isomers – Different atomic arrangement of C to C chain

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2. Position isomers – different in position of substituent atom
CH3CH2CH2Cl CH3 CHCH3
Cl
1-chloropropane 2-chloropropane

3. Functional group isomers – same chemical formula represent different

type of functional group

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 Isomers with the same molecular formula and same connectivity of atoms
but different arrangement of atoms in space.

 subdivided into TWO categories :-

1. Enantiomers:
Enantiomers stereoisomers whose molecules are nonsuperimposable
mirror images – chirality- R and S
2. Diastereomers:
Diastereomers stereoisomers whose molecules are not mirror images
of each other – eg : cis and trans isomers

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A B
Mirror image identical to actual Mirror image different to actual

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 Carbons at a tetrahedral stereogenic center are designated with an
asterisk (*)

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 Example of chiral molecule : 2-butanol
 I and II are mirror images of each other (figures a and b)
 I and II are not superimposable and so are enantiomers (figure c)
 2-butanol is a chiral molecule

 Example of Achiral (Not chiral) molecule : 2-propanol

 V and VI are mirror images of each other (figures a)
 V and VI are superimposable (figure b)

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 Drawing an enantiomer

Steps:

Example: Draw a mirror image/enantiomer or compound below

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 Tests for Chirality: Planes of Symmetry

 Plane of symmetry
 An imaginary plane that bisects a molecule in such a way that the two
halves of the molecule are mirror images of each other
 A molecule with a plane of symmetry cannot be chiral

 Example:-

A B
2-Chloropropane 2-chlorobutane
 has a plane of symmetry  do not has a plane of symmetry
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 Exercise:-
Which of the following compounds are chiral?
Determine their chiral centre/stereogenic center.
O
Br OH
H3CH2CH2C CH2CH2CH2CH3
C

H
*
*
X
H CH3

*
*
X OH
O
*

*
CH3
H CH3

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 The Biological Importance of Chirality
 Most drugs obtained from natural sources consist of a single enantiomer.
It is important to realize that a pair of enantiomers will rarely exhibit the
same potency.
 The binding specificity of a chiral receptor site for a chiral molecule is
usually only favorable in one way
 Very high levels of chiral recognition are common in biological processes.

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 Nomenclature of Enantiomers: The R,S
System
1. Assign priority group bonded to the carbon (use cahn-Ingold
Prelog sequence rules)

2. Higest priority – no1 and lowest prority no4

3. Draw a curved arrow from group 1 to group 2 to group 3.

4. Clockwise -R, counterclockwise – S.

4 4
H OH H
O
R 1 1
HO C
2
2 C OH
S
CH3 O
HO CH3 15
3
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Practice

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Assign R and S configuration to the chirality centre
in each of the following molecules

S R

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 Practice

Draw a pair of enantiomer of the following

molecules:-
a)2-Butanol ,
b)3-chloro-1-pentene
c)2-hydroxypentane

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1 2 3 4
*Enantiomer of 1 Diastereomer of 1
*not mirror image
 Example:

 There are two pairs of enantiomers (1(S,R), 2(R,S)) and (3(R,R), 4(S,S))
 Enantiomers are not easily separable so 1 and 2 cannot be separated from
each other

 Diastereomers: stereoisomers which are not mirror images of each other

 For instance, 1 and 3 or 1 and 4  Have different physical properties and
can be separated

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 Naming Compounds with More than One Stereogenic Center
 When multiple chiral centers are present, each configuration must be
preceded by a locant (a number) to indicate its location on the parent
chain
 The molecule is manipulated to allow assignment of each stereogenic
center separately

 (2R, 3R)-2,3-dibromobutane

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 Meso Compounds
 Sometimes molecules with 2 or more stereogenic centers will have less than
the maximum amount of stereoisomers  have fewer than 2n
stereoisomers
 Eg: Structures below has two chiral centers  we would expect 22 (=4)
stereoisomers (or we expect two pairs of enantiomers) BUT
 second pair is actually just one compound. It has reflectional symmetry and is
therefore a meso compound

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 Meso compound: achiral despite the presence of stereogenic centers
 Not optically active
 Superposable on its mirror image
 Has a plane of symmetry

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Students’ Approaches to Learning (SAL)

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 Properties of Enantiomers: Optical Activity
 Enantiomers have almost all identical physical properties (melting point,
boiling point, density)
 However enantiomer exhibit different behavior when exposed to plane-
polarized light  rotate the plane of plane-polarized light in equal but
opposite directions
 When light passes through a polarizing filter, only photons of a particular
polarization are allowed to pass through the filter, giving rise to plane-
polarized light

Polarized light
 When plane-polarized light is passed through a second polarizing filter,
the orientation of the filter will determine whether light passes through or
is blocked

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Unpolarized light
 Optical activity is the ability of a chiral substance to rotate the plane of plane-
polarized light and is measured using an instrument called a polarimeter.

 The Polarimeter

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 Specific Rotation

 The specific rotation for a compound is defined as the observed rotation under
sets standard conditions.
 An empty sample tube or one containing an achiral molecule will not rotate the
plane-polarized light
 An optically active substance (e.g. one pure enantiomer ) will rotate the plane-
polarized light
 The amount the analyzer needs to be turned to permit light through is
called the observed rotation “α”
 The standard value specific rotation “[α]” can be calculated
 If the analyzer is rotated clockwise the rotation is (+) and the molecule is
dextrorotatory
 If the analyzer is rotated counterclockwise the rotation is (-) and the
molecule is levorotatory

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 The specific rotation of the two pure enantiomers are equal but opposite

 There is no straightforward correlation between the R,S designation of an

enantiomer and the direction [(+) or (-)] in which it rotates plane polarized light

 Racemic (Racemate) mixture - A solution containing equal amounts (1:1) of both

enantiomers
 Optically inactive  No net optical rotation as their optical activities would nullify
(cancel) each other.
 Often designated as (+)

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 Optical Purity

 Each enantiomer on their own is said to be optically pure.

 If different quantity of two enantiomers (A + B) are mixed, the purity of the

larger quantity enantiomer (say, enantiomer A) will be cancelled off by the
smaller quantity enantiomer (B). Only the excess quantity of A will
contribute to optical activity.

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 Racemic Forms and Enantiomeric Excess
 Often a mixture of enantiomers will be enriched in one enantiomer
 One can measure the enantiomeric excess (ee)
ee

 Example : The optical rotation of a sample of 2-butanol is +6.76o. What is

the enantiomeric excess if it [α] is +13.52o?

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PRACTICE QUESTIONS

1.The specific rotation of optically pure adrenaline in water (at 25°C) is

−53. A chemist devised a synthetic route to prepare optically pure
adrenaline, but it was suspected that the product was contaminated with
a small amount of the undesirable enantiomer. The observed rotation
was found to be −45°. Calculate the % ee of the product

2.The specific rotation of a (+) lactic and (-) lactic acids is + 1.91o. The
specific rotation of pure (+) lactic acid is +3.82o. What is the percentage
of (-) lactic acid in the mixture?

3.The specific rotation of ephedrine in ethanol (at 20°C) is −6.3. A

chemist prepared a mixture of ephedrine and its enantiomer, and this
mixture had a specific rotation of −6.0. Calculate the % ee of this
mixture.

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LET’S CONTINUE NEXTWEEK!!

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