Ventures Maths GR 4

PART A:
STEREOCHEMIST
RY
HCH 103: STEREOCHEMISTRY- Miss R Chinheya 1

Stereochemistry
• Stereochemistry:
• The study of the three-dimensional
structure of molecules

ISOMERS
Constitutional
Stereoisomers
isomerism
Configurational Conformational
isomers isomers
Diastereomers Enantiomers

• Structural (constitutional) isomers:
• same molecular formula but different
bonding sequence
• Stereoisomers:
• same molecular formula, same
bonding sequence, different spatial
orientation
Conformational
isomerism

• Conformations are different spatial
arrangements of a molecule that are
generated by rotation about single bonds.
• Suppose we want to rotate ethane:

• Suppose we want to write a structure of
H2O2.
• Structures A, B and C represents different
conformations of hydrogen peroxide

Conformations of ethane
• Two conformers types of ethane are staggered and
eclipsed.

• Staggered - Hydrogens are farthest from each
other; the lowest energy conformation.
• Eclipsed - Hydrogens are closest to each other;
the highest energy conformation
• Staggered and eclipsed forms can be potrayed

by various ways :
1.Wedge (infront of the plane) and dash (back
of the plane)

2. Sawhorse projection
• The central carbon-carbon bond (C-C) is draw
as a straight line slightly tilted to right for the
sake of clarity.
• The front carbon is shown as the lower left
hand carbon and the rear carbon is shown as
the upper right hand carbon.
• The three bonds around each carbon atom
( C- H in ethane or C-C in higher alkanes) are
shown by three lines.

3. Newman projection
• Represent the front carbon by a point and the

back carbon by a circle. Each carbon has three
substituents that are placed symmetrically
around it.

Staggered conformations Eclipsed conformations

• Eclipsed bonds are characterized by a
torsion angle of 0°. When the torsion angle
is approximately 60°, the spatial
relationship is gauche
• when it is 180°, it is anti.
• Staggered conformations have only gauche
or anti relationships between bonds on
adjacent atoms

The staggered is more stable than the eclipsed.
• The staggered conformation allows the electron
pairs in the C-H bonds of one carbon to be
farther away from the electron pairs in the C-H
bonds of the other than the eclipsed
conformation allows.
• Electron-pair repulsions influence the bond
angles at a central atom.
• The destabilization that comes from eclipsed
bonds on adjacent atoms is called torsional
strain.
• The total strain of all of the spatially dependent
features is often called steric strain.
Potential energy of
ethane
• The potential energy of ethane changes for a
360° rotation about the carbon-carbon bond.
• Three equivalent eclipsed conformations and
three equivalent staggered conformations occur
during the 360° rotation.
• The eclipsed conformations appear at the
highest points on the curve (potential energy
maxima), the staggered ones at the lowest
(potential energy minima).

LECTURE 2:
CONFIGURATIONAL ISOMERISM

Configurational isomers
• Configurational isomers interconvert through
the breaking and reforming of covalent bonds,
a high-energy process.
• Cannot be interconverted one into another by
rotation, i.e. without breaking bonds.

configuration – the arrangement in space of the four
different groups about a chiral center.
How do we show configurations?
“wedge” formulas Fischer projections
“cross structures”
use only for chiral centers!
Br Br
H Cl H
F Cl F
In the Fischer projection, the horizontal bonds to the
chiral center are always above the plane and the
vertical bonds to the chiral center are below the
plane. (the horizontals are “hugging you.”
CH3 CH3
Br Cl Br Cl
H H

CHIRALITY
• Chiral- A tetrahedral carbon atom bearing four
different substituents.
• This carbon with four different groups is a
tetrahedral stereogenic center.
• A molecule or object that is not superimposable on
its mirror image are said to be chiral.
• Although everything has a mirror image, mirror
images may or may not be superimposable.
• Superimposable: The ability for an object to be
placed over another object, usually in such a way
that both will be visible.
Chiral Carbons
• Carbons with four different groups attached are
chiral.
• It’s mirror image will be a different compound
(enantiomer).

Chiral
• “Handedness”: Right glove doesn’t fit the left

hand.
• Mirror-image object is different from the
original object.
Asymmetric Carbons
• The most common feature that leads to chirality in
organic compounds is the presence of an asymmetric
(or chiral) carbon atom.
• A carbon atom that is bonded to four different
groups
• In general:
• no asymmetric C usually achiral
• 1 asymmetric C always chiral
• > 2 asymmetric C may or may not be
chiral
Asymmetric Centers on
Rings

Asymmetric Carbons
Example: Identify all asymmetric carbons
present in the following compounds.
CH3 CH2CH3
H OH H H H H
H
H C C C C H H3C
H H H H
Br
Br Br
Br H CH
3
Achiral Compounds
Take this mirror image and try to

superimpose it on the one to the left
matching all the atoms. Everything will
match.
When the images can be superimposed the
compound is achiral.
Achiral
• Many molecules and objects are achiral:
• identical to its mirror image
• not chiral
H H H H
Cl Cl Cl Cl
Planes of Symmetry
• A molecule that has a plane of symmetry

is achiral.
Internal Plane of
Symmetry
• Cis-1,2-dichlorocyclopentane contains two
asymmetric carbons but is achiral.
• contains an internal mirror plane of symmetry
s
H H
Cl Cl
• Any molecule that has an internal mirror plane of

symmetry is achiral even if it contains asymmetric
carbon atoms.
Internal Planes of
Symmetry

Internal Plane of
Symmetry
Example: Which of the following compounds contain an
internal mirror plane of symmetry?
HO2C CO2H H Br CH2CH3

H CH 3
C C C C
HO OH H H 3C H
H H H3CH2C Br
HO2C CO2H
H
O
C C F C OHF C
HO H
F Cl
H OH HO C H H
Chiral vs. Achiral
• To determine if a compound is chiral:
• 0 asymmetric carbons: Usually achiral
• 1 asymmetric carbon: Always chiral
• 2 asymmetric carbons: Chiral or
achiral
• Does the compound have an internal plane of
symmetry?
• Yes: achiral
• No:
• If mirror image is non-superimposable,
then it’s chiral.
• If mirror image is superimposable, then it’s
achiral.
Question: Classify each of the following pairs as chiral or
achiral? CH3 CH3
a)
CH3 H3C
achiral
Cl Br Cl
Br
b) CH3 CH3
Br Br chiral
Cl Cl H
H
H Br H
Br
c)
chiral
F F

ENANTIOMERS

• Enantiomers are chiral:
• Not superimposable on its mirror image.
• Consider 2-bromobutane below:

PROPERTIES OF
ENANTIOMERS
1. Enantiomers have almost all identical physical properties
• (melting point, boiling point, density) and chemical
properties. except in their interaction with chiral substances.
• They have identical physical properties, except for how they
interact with plane-polarized light.
2. 3. Different interaction with other chiral molecules:

• Active site of enzymes is selective for a specific
enantiomer.
• Taste buds and scent receptors are also chiral.
Enantiomers may have different smells.
Physical properties of
enantiomers

1. Optical Activity
• Plane-polarized (polarized) light is light that
has an electric vector that oscillates in a
single plane.
• Plane-polarized light arises from passing
ordinary light through a polarizer.
(Nicol Prism)

Normal and plane polarized light
non-polarized(normal light) polarized

Polarimeter
• A polarimeter is an instrument that allows polarized
light to travel through a sample tube containing an
organic compound.
• It permits the measurement of the degree to which an
organic compound rotates plane-polarized light.

Optical Activity
• With achiral compounds, the light that exits the sample
tube remains unchanged. A compound that does not
change the plane of polarized light is said to be optically
inactive.

Optical Activity
• With chiral compounds, the plane of the polarized light is
rotated through an angle . The angle  is measured in
degrees (°), and is called the observed rotation. A
compound that rotates polarized light is said to be
optically active.

Optical Activity
• The rotation of polarized light can be clockwise or
anticlockwise.
• If the rotation is clockwise the compound is called
dextrorotatory. The rotation is labeled d or (+).
• If the rotation is counterclockwise, the compound is
called levorotatory. The rotation is labeled l or (-).
• Two enantiomers rotate plane-polarized light to an equal
extent but in opposite directions. Thus, if enantiomer A
rotates polarized light +5°, the same concentration of
enantiomer B rotates it –5°.
• No relationship exists between R and S prefixes and the
(+) and (-) designations that indicate optical rotation. 45
HCH 103: STEREOCHEMISTRY- Miss R Chinheya
Racemic Mixtures
• An equal amount of two enantiomers is called a racemic
mixture or a racemate.
• A racemic mixture is optically inactive. WHY??
• Because two enantiomers rotate plane-polarized light to
an equal extent but in opposite directions, the rotations
cancel, and no rotation is observed.

Specific rotation
• Specific rotation is a standardized physical constant for the
amount that a chiral compound rotates plane-polarized light.
• Specific rotation is denoted by the symbol [] and defined using
a specific sample tube length (l, in dm), concentration (c in
g/mL), temperature (250C) and wavelength (589 nm).

EXERCISE
When one of the enantiomers of 2-butanol is placed in a polarimeter, the

observed rotation is 4.05° counterclockwise. The solution was made by diluting 6
g of 2-butanol to a total of 40 mL, and the solution was placed into a 200-mm
polarimeter tube for the measurement. Determine the specific rotation for this
enantiomer of 2-butanol.
Solution
Since it is levorotatory, this must be (–)-2-butanol The concentration
is 6 g per 40 mL = 0.15 g/ml, and the path length is 200 mm = 2 dm.
The specific rotation is
– 4.05°
[a]25
D
= = –13.5°
(0.15)(2)

2. Optical Purity
• Enantiomeric excess (optical purity) is a measurement of
how much one enantiomer is present in excess of the
racemic mixture. It is denoted by the symbol ee.
ee = % of one enantiomer - % of the other enantiomer.
-If a mixture contains 75% of one enantiomer and 25% of the other,
the enantiomeric excess is 75% - 25% = 50%. Thus, there is a 50%
excess of one enantiomer over the racemic mixture.
• The enantiomeric excess can also be calculated if the
specific rotation [] of a mixture and the specific rotation
[] of a pure enantiomer are known.
ee = ([] mixture/[] pure enantiomer) x 100.
• Since enantiomers have identical physical properties, they
cannot be separated by common physical techniques like
distillation.
• Diastereomers and constitutional isomers have different
physical properties, and therefore can be separated by
common physical techniques.
The physical properties of

the three stereoisomers of
tartaric acid

Resolution of Enantiomers
• React the racemic mixture with a pure chiral

compound, such as tartaric acid, to form
diastereomers, then separate them.
Chromatographic
Resolution of Enantiomers

Chemical properties of
enantiomers

• Two enantiomers have exactly the same chemical properties
except for their reaction with chiral non-racemic reagents.
• Many drugs are chiral and often must react with a chiral
receptor or chiral enzyme to be effective. One enantiomer of
a drug may effectively treat a disease whereas its mirror
image may be ineffective or toxic.

Enantiomers and the Sense of Smell
• Odor of a particular molecule is determined more by its
shape than by the presence of a particular functional
group.
• Because enantiomers interact with chiral smell receptors,
some enantiomers have different odors.

R/S PROJECTION

(R) and (S) Nomenclature
• Different molecules (enantiomers) must have different

names.
• Usually only one enantiomer will be biologically active.
• The Cahn-Ingold-Prelog convention is used to identify the
configuration of each asymmetric carbon atom present in
a stereoisomer.
• (R) and (S) configuration
• The two enantiomers of alanine are:
CO2H CO2H
C C
H H CH3
H3C NH2 H2N
Natural alanine Unnatural alanine

(S)-alanine (R)-alanine

Cahn–Ingold–Prelog
(CIP)
Rules
• 1. Assign a numerical priority to each group DIRECTLY
bonded to the asymmetric carbon:
• group 1 = highest priority
• group 4 = lowest priority
• Rules for assigning priorities:

• Compare the first atom in each group (i.e. the
atom directly bonded to the asymmetric carbon)
• Atoms with higher atomic numbers have higher
prior
Priority
1 3
Cl CH3
3
C 2 C H4
H3 C
OCH2CH3 1 F 2NH2
H
4
Example priorities:
I > Br > Cl > S > F > O > N > 13

C> C > 3H >
12
2
H > 1H
CIP RULE
2. In case of ties, use the next atoms along the
chain as tiebreakers.
2
CH2CH2Br
C H4
3
CH3CH2
CH(CH3)2
1
CH(CH3)2 > CH2CH2Br > CH3CH2

Y
C Y
CIP RULE C Y C
3.Treat double and triple bondsY asCif both atoms in the

Y
bond
C Y
were duplicated
C
or triplicated:
C O Y C
C Y
O C H Y C
Y
C OH C Y Y
H C Y C Y C Y C Y C
CH2OH C Y C
Y C Y C
Y C
O 2 H C C O
Y
C Y C C Y2
O C H
Y 1
C C OH C 1
OH
4 H CH2OH C 4 HY CH2OH
3 C Y3
Y C
Treatment of Multiple
Bonds

Assign (R) or (S)
• Working in 3-D, rotate the molecule so that the

lowest priority group is in back.
• Draw an arrow from highest to lowest priority group.
• Clockwise = (R), Counterclockwise = (S)
Assign Priorities
Atomic number: F > N > C > H
Once priorities have been assigned, the lowest priority group (#4)
should be moved to the back if necessary.

Assign Priorities
Counterclockwise
(S)
Draw an arrow from Group 1 to Group 2 to Group 3 and back to Group

1. Ignore Group 4.
Clockwise = (R) and Counterclockwise = (S)

Example
3
1 CH2CH3
OH
rotate
C 3 2
C 4
2 CH2CH3 CH3CH2CH2 H
CH3CH2CH2
H OH
4 1
Clockwise
(R)
When rotating to put the lowest priority group in the back, keep one
group in place and rotate the other three.

Solved Problem 1
Draw the enantiomers of 1,3-dibromobutane and

label them as (R) and (S)

• Solution
• The third carbon atom in 1,3-dibromobutane is asymmetric. The
bromine atom receives first priority, the (–CH2CH2Br) group second
priority, the methyl group third, and the hydrogen fourth. The
following mirror images are drawn with the hydrogen atom back,
ready to assign (R) or (S) as shown.

CH3)2
Example: Identify the asymmetric carbon(s) in each of
the following compounds and determine whether it has
the (R) or (S) configuration. O
CH3
CH3 H
C H
CH2CCH3 C CH(CH )
OHH CH2CH3 3 2
OH CH3 Br
Br Br
O CH3
C COH
CH3 CO2H H CH2C
H3 H OH
H HCH 103: STEREOCHEMISTRY- Miss R Chinheya 70
Example: Name the following compounds.
CH2CH3
C
Br CH3
H
Br CH3
H CH3
• When naming compounds containing multiple chiral
atoms, you must give the configuration around each
chiral atom:
• position number and configuration of each chiral atom in
numerical order, separated by commas, all in ( ) at the start
of the compound name
H Br H
Cl
(2S, 3S)-2-bromo-3-chlorobutane
H3C CH3
Depicting Structures with
Asymmetric Carbons
Example: Draw a 3-dimensional formula for (R)-2-
chloropentane.
Step 1: Identify the asymmetric carbon.
Cl
*
CH3 C CH2CH2CH3
H
Step 2: Assign priorities to each group
attached to the asymmetric carbon.
1
C Cl
2
3 CH C CH2CH2CH3
3
H 4
Depicting
Cl Structures with
Asymmetric
CH C CHCarbons
CH CH
3 2 2 3
Step 3: Draw a “skeleton” with the asymmetric
H and the lowest priority
carbon in the center
group attached to the “dashed” wedge (i.e.
pointing away from you).
Cl
CH C
CH3 C H 2CH2CH3
H
Step 4: Place the highest priority group at the top.
Cl
C
H
Cl
Asymmetric Carbons
Step C (R)CH
CH5:3 For CH2CH3 place the 2nd and 3rd
configuration,
2
priority groups around the asymmetric carbon in a
clockwiseHdirection.
Cl
C
H
CH3 CH2CH2CH3
Step 6: Double-check your structure to

make sure that it has the right groups and
the right configuration.
Asymmetric Carbons
Example: The R-enantiomer of ibuprofen is not
biologically active but is rapidly converted to the active
(S) enantiomer by the body. Draw the structure of the
R-enantiomer.
HO2CCH CH2CH(CH3)2
CH3

Asymmetric Carbons
Example: Captopril, used to treat high blood
pressure, has two asymmetric carbons, both with the
S configuration. Draw its structure.
O
N C CHCH2SH
CH3
CO2H

Label each compound as R or S.
Cl 2 2
a)
S
H
H3C Br
3 1 3 1
b) CH2Br
rotate
CH2Br
2 2
ClH2C H3C
CH2Cl
OH HO
H3C 1 3 1 3
R

MANY ASYMETRICAL
CARBONS

Two or More Chiral
Carbons
• When compounds have two or more chiral centers
they can be enantiomers, diastereomers, or meso
isomers.
• Enantiomers have opposite configurations at each
corresponding chiral carbon.
• Diastereomers have some matching, some opposite
configurations.
• Meso compounds have internal mirror planes.
• Maximum number of isomers is 2n, where n = the
number of chiral carbons.
Diastereomers
• Molecules with two or more chiral carbons.

Number of Stereoisomers
The 2n rule will not apply to compounds that may

have a plane of symmetry. 2,3-dibromobutane has
only 3 stereoisomers: (±) diastereomer and the
meso diastereomer.
Adjacent asymmetrical centres of
tartaric acid and related structures

Alkenes
• Cis-trans isomers are not mirror images, so these
are diastereomers.

Properties of Diastereomers
• Diastereomers have different physical
properties, so they can be easily separated.
• Enantiomers differ only in reaction with other
chiral molecules and the direction in which
polarized light is rotated.
• Enantiomers are difficult to separate.
• Convert enantiomers into diastereomers to be
able to separate them.
Meso Compounds
• Meso compounds have a plane of symmetry.

• If one image was rotated 180°, then it could be
superimposed on the other image.
• Meso compounds are achiral even though they
have chiral centers.
• Compounds with even more asymmetric
atoms. The representation becomes
awkward.
• An alternative projection system that is
widely used is called the Fischer
Projection.

FISCHER PROJECTION

Fischer Projections
• Flat representation of a 3-D molecule.
• A chiral carbon is at the intersection of horizontal and
vertical lines.
• Horizontal lines are forward, out-of-plane and vertical
lines are behind the plane.

Fischer Projections (Continued)

Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon is at top.
• Rotation of 180 in plane doesn’t change molecule.
• Do not rotate 90!

180° Rotation
• A rotation of 180° is allowed because it will not change

the configuration.

90° Rotation
• A 90° rotation will change the orientation of

the horizontal and vertical groups.
• Do not rotate a Fischer projection 90°.
Fischer Mirror Images
• Fisher projections are easy to draw and make it
easier to find enantiomers and internal mirror
planes when the molecule has 2 or more chiral
centers.
C H 3
H Cl
Cl H
C H 3

Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so assignment
rules are backwards!
• Clockwise 1-2-3 is (S) and counterclockwise 1-2-3 is (R).
• Example:
(S)
CH 3
H Cl
Cl H
(S) CH 3

Fischer Projections with
2 Chiral Centers

D AND L NOTATION
D and L Notation: used to describe the configurations of

carbohydrates and amino acids. Rules:
 In a Fischer projection, the carbonyl group is always placed on/close to
the top
 If the OH attached to the bottom-most asymmetric center is on the right,
then a D-sugar; If on the left, a L-sugar
 All the natural sugars are D-sugars

• The D- and L- notation is based on these structures.
• (Note that D- and L- means something quite
different to d- and l-).
By definition (R)-(+)- is D-glyceraldehyde and (S)-(-)-
is L-glyceraldehyde.

Fischer projection in
sugars: A Carbohydrate

E/Z ISOMERISM RESULTING
FROM DOUBLE BONDS
• E/Z (cis/trans) ISOMERISM RESULTING FROM
DOUBLE BONDS
• Assignment - CIP system analogy:
• 1. each side of the double bond is considered
separately, priority of the substituents is
• then determined according to CIP rules
• 2. Z (together): higher ranking substituents are at the
same side of the double bond;
• E (opposite): higher-ranking substituents are on
opposite sides of the double bond

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PART A:

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 1

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 2

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 3

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 5

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 6

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 7

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 8

• Staggered and eclipsed forms can be potrayed

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 9

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 10

• Represent the front carbon by a point and the

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 11

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 12

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 14

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 16

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 18

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 19

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 21

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 23

• “Handedness”: Right glove doesn’t fit the left

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 26

Take this mirror image and try to

• A molecule that has a plane of symmetry

• Any molecule that has an internal mirror plane of

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 32

HO2C CO2H H Br CH2CH3

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 35

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 36

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 37

2. 3. Different interaction with other chiral molecules:

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 39

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 40

non-polarized(normal light) polarized

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 42

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 43

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 44

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 46

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 47

When one of the enantiomers of 2-butanol is placed in a polarimeter, the

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 48

The physical properties of

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 50

• React the racemic mixture with a pure chiral

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 52

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 53

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 54

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 55

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 56

• Different molecules (enantiomers) must have different

Natural alanine Unnatural alanine

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 58

• Rules for assigning priorities:

I > Br > Cl > S > F > O > N > 13

CH(CH3)2 > CH2CH2Br > CH3CH2

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 61

3.Treat double and triple bondsY asCif both atoms in the

HCH 103: STEREOCHEMISTRY- Miss R Chinheya 63

• Working in 3-D, rotate the molecule so that the