Stereochemistry
The arrangement of atoms in space
By: Dr. Manal F. Abou Taleb
Organic Chemistry, 5th Edition
L. G. Wade, Jr. chapter 5
Isomerism
• Isomers are different compounds that have the
same molecular formula.
• Constitutional isomers are isomers that differ
because their atoms are connected in a
different order.
Cahn-Ingold-Prelog Rules
• Assign a priority number to each group
attached to the chiral carbon.
• Atom with highest atomic number assigned
the highest priority #1.
• In case of ties, look at the next atoms along
the chain.
• Double and triple bonds are treated like
bonds to duplicate atoms.
=>
4
Geometric Isomers
cis-trans isomers
5
Geometric isomers:
cis or trans?
E and Z Based on Priority:
Cahn- Ingold-Prelongo:
1. Atomic Number
2. Atomic weight
3. Atomic number of the next
atom
35 2
17Cl 1
Br
---------------C
C
53 I
1
9F 2
(E) ? ethene
(E)-1-bromo-2-chloro2-fluoro-1-iodoethene
Higher priority at the opposite side of pi bond (E)
Higher priority at the same side of pi bond (Z)
6
cis or trans?
E and Z Based on Priority:
2
2
12
1
C2H5
H
12 ---------------H3C
12C CH
1
1
(E) ? pentyne
(E)-3-ethyl-2-pentene-4-yne
7
8
• Stereoisomers can be either enantiomers or diasteriomers
• A) Enanatiomers are stereoisomers whose molecules are
nonsuperimposable mirror images of each other (different
molecules).
H
H
H
Cl
Cl
Cl
H
Cl
Cl
cis-1,2-dichlorocyclopentane
H
H
Cl
Cl
H
H
Cl
trans -1,2-dichlorocyclopentane
Enantiomers
Nonsuperimposable mirror images are
called enantiomers, they occur in pairs.
These two structures are enantiomers.
• B) Diastereomers (Geometric) are stereoisomers
whose molecules are not mirror images of each
other.
Enanatiomers
“Optical isomer”
Same carbon
Same connection
Are mirror image
Nonsuperimposable
All configurations
are opposite
Diastereomers
Same carbon
Same connection
Are Not mirror image
Nonsuperimposable
Not All configurations
are opposite
Chirality
• “Handedness”: right glove doesn’t fit the left hand.
• Mirror-image object is different from the original
object.
=>
Molecule may be chiral or achiral
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Stereoisomerisms
Chiral: An object that cannot be superposed
‫متطابق‬on its mirror image
Chiral Carbon atom
Chiral center
Chiral molecules does
Not contain a plane of
symmatry
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Chiral Carbons
• Tetrahedral carbons with 4 different attached groups
are chiral.
• A tetrahedral carbon atom with four different groups
attached to it is an asymmetric carbon.
• Its mirror image will be a different compound
(enantiomer).
=>
15
Bromochlorofluoromethane is chiral
Cl
Br
H
F
It is not superimposable
point for point on its
mirror image.
Note the four different
attachments on C.
Bromochlorofluoromethane is chiral
Cl
Cl
Br
Br
H
F
H
F
To demonstrate nonsuperimposability, rotate this
model 180° around a vertical axis.
Bromochlorofluoromethane is chiral
Cl
Cl
Br
Br
H
F
H
F
The structure on the right has been
rotated.
• Example: 2-butanol
 I and II are mirror images of each other (figures a and b)
 I and II are not superposable and so are enantiomers (figure c)
 2-butanol is chiral molecule
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Chlorodifluoromethane
is achiral
Chlorodifluoromethane
is achiral
The two structures at the top are mirror images, but
because they can be superimposed on each other they
are identical and are not enantiomers.
Mirror Planes of Symmetry
 If two groups are the
same, carbon is
achiral. (animation)
 A molecule with an
internal mirror plane
cannot be chiral.*
Chiral molecules does Not
contain a plane of symmatry σ
Notes ! If there is no plane of symmetry, molecule may
be chiral or achiral. See if mirror image can be
superimposed. =>
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Symmetry tests for achiral structures
 Any molecule with a plane of symmetryor a center
of symmetry must be achiral.
Achiral center: a C atom is attached by 2 or more same
groups.
---------------------------------------------------------------------
Chiral
 Non-superimposable
with its mirror image
asymmetric carbon
4 different attached
groups
Enanatiomers
achiral
Superimposable
with its mirror image
plane of symmetry
2 or more same attach
groups.
not enantiomers
Cl
CH3CCH2CH3
H
CH3
CH3CH2CCH2CH2CH3
H
chirall
chirall
2-chlorobutane
3-methylhexane
CH3
CH3CCH2CH3
H
achirall
2-methylbutane
Clasiffy each of the following pairs as chiral or
achiral. CH
CH
achiral
a)
CH
H C
3
3
3
Cl
3
Br
CH3
CH3
b)
Cl
Br
chiral
Br
Br
Cl
H
H
Br
Cl
H
Br
H
chiral
c)
F
F
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Label the stereogenic centers in each molecule and
decide if it is chiral.
a) CH3CH2CH(Cl)CH2CH3
achiral
Cl
H
b) CH3CH(OH)CH=CH2
H
OH
chiral
c) (CH3)2CHCH2CH2CH(CH3)CH2CH3
H
CH3
chiral
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Plane of symmetry
A plane of symmetry bisects a molecule into two
mirror image halves. Chlorodifluoromethane
has a plane of symmetry.
Plane of symmetry
A plane of symmetry bisects a molecule into two
mirror image halves.
1-Bromo-1-chloro-2-fluoroethene has a plane
of symmetry.
These mirror images are not the same, even after rotation!
These are two distinct 3-methylhexane
enantiomers
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•(a) 2-Propanol and its mirror image, (b) When either one
is rotated, the two structures are superposable and so do not
represent enantiomers. They represent two molecules of the
same compound. 2- Propanol does not have a stereocenter.
The Importance of Chirality in Biological Systems
On the molecular level, most biologically important molecules are chiral.
The biological activity of chiral molecules is specifically associated with a
specific enantiomer. This specificity results from reaction between a
chiral molecule and a chiral receptor that only accomodates one
enantiomer. This enantioselectivity is a key factor in drug design.
How is each pair of the following structures is
related:
(i) The Same
(ii) Geometric isomers
(iii) Structural isomers
(iv) Not related at all
(a)
(b)
(c)
(d)
Which one of the following compounds can exist as
a pair of geometric isomers?
Cl
Cl
Cl
Cl
Cl
(i)
(ii)
(iii)
(iv)
Which compound of the following cannot exhibit cis / trans
isomerism
(i) 1,4-Dibromocyclohexane
(iii) 1,1-Dibromocyclohexane
(ii) 1,2-Dibromocyclohexane
(iv)1,3-Dibromocyclohexane
Which of the following molecules is trans-1, 2dimethylcyclohexane?
(i)
(ii)
(iii)
(iv)
Absolute Conformation
Assign (R) or (S)
• Working in 3D, rotate molecule so that lowest
priority group is in back.
• Draw an arrow from highest to lowest priority
group.
• Clockwise = (R), Counterclockwise = (S)
=>
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Labeling Stereogenic Centers with R or S
• Since enantiomers are two different compounds, they
need to be distinguished by name. This is done by adding
the prefix R or S to the IUPAC name of the enantiomer.
• Naming enantiomers with the prefixes R or S is called the
Cahn-Ingold-Prelog system.
• To designate enantiomers as R or S, priorities must be
assigned to each group bonded to the stereogenic center,
in order of decreasing atomic number.
 The atom of highest atomic number gets the highest
priority (1).
37
If two atoms on a stereogenic center are the same,
assign priority based on the atomic number of the
atoms bonded to these atoms. One atom of higher
atomic number determines the higher priority.
38
 If two isotopes are bonded to the stereogenic center,
assign priorities in order of decreasing mass number.
Thus, in comparing the three isotopes of hydrogen, the
order of priorities is:
39
To assign a priority to an atom that is part of a multiple bond, treat
a multiply bonded atom as an equivalent number of singly bonded
atoms. For example, the C of a C=O is considered to be bonded to
two O atoms.
 Other common multiple bonds are drawn below:
40
Figure 5.6
Examples of assigning
priorities to stereogenic centers
41
42
Labeling Stereogenic Centers with R or S
43
44
Figure 5.7
Examples: Orienting the lowest
priority group in back
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Label each compound as R or S.
Cl
a)
2
S
H
Br
H3C
3
CH2Br
b)
ClH2C
2
1
3
1
CH2Br
rotate
H3C
OH
H3C
HO
2
2
CH2Cl
1
3
1
3
R
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