Stereochemistry, 3d dimensional properties.ppt

© 2013 Pearson Education, Inc.
Stereochemistry
Stereochemistry refers to the
3-dimensional properties and
reactions of molecules. It has
its own language and terms that
need to be learned in order to
fully communicate and
understand the concepts.

Definitions
• Stereoisomers – compounds with the same
connectivity, different arrangement in
space
• Enantiomers – stereoisomers that are non-
superimposible mirror images; only
properties that differ are direction (+ or
-) of optical rotation
• Diastereomers – stereoisomers that are not
mirror images; different compounds
with different physical properties

More Definitions
• Asymmetric center – sp3
carbon with 4
different groups attached
• Optical activity – the ability to rotate the
plane of plane –polarized light
• Chiral compound – a compound that is
optically active (achiral compound will
not rotate light)
• Polarimeter – device that measures the
optical rotation of the chiral compound

Chirality
• “Handedness”: Right-hand glove does
not fit the left hand.
• An object is chiral if its mirror image is
different from the original object.
Chapter 5 4

Achiral
• Mirror images that can be superposed
are achiral (not chiral).
Chapter 5 5

Stereoisomers
Enantiomers: Compounds that are
nonsuperimposable mirror images. Any molecule
that is chiral must have an enantiomer.
Chapter 5 6

Chiral Carbon Atom
• Also called asymmetric carbon atom.
• Carbon atom that is bonded to four different groups
is chiral.
• Its mirror image will be a different compound
(enantiomer).
Chapter 5 7

Stereocenters
• An asymmetric carbon atom is the most
common example of a chirality center.
• Chirality centers belong to an even broader
group called stereocenters. A stereocenter (or
stereogenic atom) is any atom at which the
interchange of two groups gives a stereoisomer.
• Asymmetric carbons and the double-bonded
carbon atoms in cis-trans isomers are the most
common types of stereocenters.
Chapter 5 8

Examples of Chirality Centers
Asymmetric carbon atoms are examples of chirality
centers, which are examples of stereocenters.
Chapter 5 9

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 superposed, the
compound is achiral.
Chapter 5 10

Planes of Symmetry
• A molecule that has a plane of symmetry is
achiral.
Chapter 5 11

Cis Cyclic Compounds
• Cis-1,2-dichlorocyclohexane is achiral because
the molecule has an internal plane of symmetry.
Both structures above can be superimposed
(they are identical to their mirror images).
Chapter 5 12

Trans Cyclic Compounds
• Trans-1,2-dichlorocyclohexane does not have a
plane of symmetry so the images are
nonsuperimposable and the molecule will have two
enantiomers.
Chapter 5 13

(R) and (S) Configuration
• Both enantiomers of alanine receive the same name in the
IUPAC system: 2-aminopropanoic acid.
• Only one enantiomer is biologically active. In alanine only the
enantiomer on the left can be metabolized by the enzyme.
• A way to distinguish between them is to use stereochemical
modifiers (R) and (S).
Chapter 5 14

Cahn–Ingold–Prelog
Priority System
• Enantiomers have different spatial arrangements of the
four groups attached to the asymmetric carbon.
• The two possible spatial arrangements are called
configurations.
• Each asymmetric carbon atom is assigned a letter (R)
or (S) based on its three-dimensional configuration.
• Cahn–Ingold–Prelog convention is the most widely
accepted system for naming the configurations of
chirality centers.
Chapter 5 15

(R) and (S) Configuration: Step 1
Assign Priority
• Assign a relative “priority” to each group
bonded to the asymmetric carbon.
Group 1 would have the highest priority,
group 2 second, etc.
• Atoms with higher atomic numbers
receive higher priorities.
I > Br > Cl > S > F > O > N > 13
C > 12
C > 2
H > 1
H
Chapter 5 16

Assign Priorities
Atomic number: F > N > C > H
Chapter 5 17

(R) and (S) Configuration:
Breaking Ties
In case of ties, use the next atoms along
the chain of each group as tiebreakers.
Chapter 5 18

Multiple Bonds
Treat double and
triple bonds as if
each were a bond to
a separate atom.
Chapter 5 19

Step 2
• Working in 3-D, rotate the
molecule so that the lowest
priority group is in back.
• Draw an arrow from highest
(1) to second highest (2) to
lowest (3) priority group.
• Clockwise = (R),
Counterclockwise = (S)
Chapter 5 20

Assign Priorities
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)
Counterclockwise
Counterclockwise
(
(S
S)
)
Chapter 5 21

Example
C
OH
CH3CH2CH2
H
CH2CH3
1
2
3
4
C
CH2CH3
CH3CH2CH2
OH
H
1
2
3
4
rotate
When rotating to put the lowest priority group in the back,
keep one group in place and rotate the other three.
Clockwise
Clockwise
(
(R
R)
)
Chapter 5 22

Example (Continued)
CH3
CH3CH2CH=CH
CH2CH2CH2CH3
H
1
1
2
2
3
3
4
4
Counterclockwise
Counterclockwise
(
(S
S)
)
Chapter 5 23

Properties of Enantiomers
• Same boiling point, melting point, and density.
• Same refractive index.
• Rotate the plane of polarized light in the same
magnitude, but in opposite directions.
• 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.
Chapter 5 24

Polarized Light
Plane-polarized light is composed of
waves that vibrate in only one plane.
Chapter 5 25

Optical Activity
• Enantiomers rotate the plane of polarized
light in opposite directions, but same number
of degrees.
Chapter 5 26

Polarimeter
Clockwise
Clockwise
Dextrorotatory (+)
Counterclockwise
Counterclockwise
Levorotatory (-)
Not related to (R) and (S)
Chapter 5 27

Biological Activity
(R)(+) Thalidomide (S)(-) Thalidomide
N
N
O
O
O
O
H
H
a sedative and hypnotic a teratogen
N
N
O
O
O
O
H
H

SSRI Efficacy depends on
Stereochemistry
O
N(CH3)2
F
NC
*
(+/-) Celexa
(-) Lexapro

Racemic Mixtures
• Equal quantities of d- and l-enantiomers.
• Notation: (d,l) or ()
• No optical activity.
• The mixture may have different boiling point (b. p.) and melting point (m.
p.) from the enantiomers!
Chapter 5 30

Racemic Products
If optically inactive reagents combine to
form a chiral molecule, a racemic mixture
is formed.
Chapter 5 31

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.
• Vertical lines are behind the plane.
Chapter 5 32

Fischer Projections (Continued)
Chapter 5 33

Fischer Rules
• Carbon chain is on the vertical line.
• Highest oxidized carbon is at top.
• Rotation of 180 in plane doesn’t
change molecule.
• Rotation of 90 is NOT allowed.
Chapter 5 34

180° Rotation
• A rotation of 180° is allowed because it will
not change the configuration.
Chapter 5 35

90° Rotation
• A 90° rotation will change the orientation of
the horizontal and vertical groups.
• Do not rotate a Fischer projection 90°.
Chapter 5 36

Glyceraldehyde
• The arrow from group 1 to group 2 to group 3
appears counterclockwise in the Fischer projection. If
the molecule is turned over so the hydrogen is in
back, the arrow is clockwise, so this is the (R)
enantiomer of glyceraldehyde.
Chapter 5 37

When naming (R) and (S) from
Fischer projections with the
hydrogen on a horizontal bond
(toward you instead of away
from you), just apply the normal
rules backward.
Chapter 5 38

Fischer Mirror Images
• Fisher projections are easy to draw and make
it easier to find enantiomers and internal
mirror planes when the molecule has two or
more chiral centers.
CH3
H Cl
Cl H
CH3
Chapter 5 39

Fischer (R) and (S)
• Lowest priority (usually H) comes forward, so
assignment rules are backward!
• Clockwise 1-2-3 is (S) and counterclockwise
1-2-3 is (R).
• Example:
(S)
(S)
CH3
H Cl
Cl H
CH3
Chapter 5 40

Racemic Mixture
o

(g/mL) 1.7598 1.7598 1.7723
m.p. C 168-170 168-170 210-212
[] (degrees) - 12 + 12 0
(R,R) Tartaric acid (S,S) Tartaric Acid (+/-) Tartaric acid
Racemic Mixture (Racemate): 50/50 mixture of enantiomers
CO2H
CO2H
H OH
HO H H OH
HO H
CO2H
CO2H
R,R S,S

Meso Compound
Internal Plane of Symmetry
Optically Inactive
o
rotate 180
superimposible
CO2H
CO2H
H OH
H OH HO H
HO H
CO2H
CO2H
R,S S,R
mirror
plane

Diastereomers: Cis-trans
Isomerism on Double Bonds
• These stereoisomers are not mirror
images of each other, so they are not
enantiomers. They are diastereomers.
Chapter 5 43

Diastereomers: Cis-trans
Isomerism on Rings
• Cis-trans isomers are not mirror images, so
these are diastereomers.
Chapter 5 44

Diastereomers
• Molecules with two or more chiral carbons.
• Stereoisomers that are not mirror images.
Chapter 5 45

Two or More Chiral Carbons
• When compounds have two or more chiral
centers they have 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.
Chapter 5 46

2,3,4-trichlorohexane
How many stereoisomers?
Cl
Cl
Cl
3 asymmetric centers
8 stereoisomers
* *
*
2n, n= # asymmetric centers (3)

n = 3; 2n
= 8
CH3
CH2CH3
H Cl
Cl H
H Cl Cl H
H Cl
Cl H
CH3
CH2CH3
CH3
CH2CH3
Cl H
H Cl
H Cl Cl H
Cl H
H Cl
CH3
CH2CH3
H Cl
H Cl
H Cl
CH3
CH2CH3
Cl H
Cl H
Cl H
CH3
CH2CH3
Cl H
H Cl
H Cl
CH3
CH2CH3
H Cl
Cl H
Cl H
CH3
CH2CH3
S
S
R
R
R
S

A Carbohydrate
CHO
CH2OH
H OH
HO H
H OH
H OH
(+) D-Glucose
R
S
R
R

• 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.
Meso Compounds
Chapter 5 50

Number of Stereoisomers
The 2n
rule will not apply to compounds that may have a
plane of symmetry. 2,3-dibromobutane has only three
stereoisomers: (±) diastereomer and the meso diastereomer.
Chapter 5 51

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.
Chapter 5 52

Stereochemistry, 3d dimensional properties.ppt

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