STEREOCHEMISTRY 1 for year 2 stdents.ppt

6. Stereochemistry
Based on McMurry’s Organic Chemistry, 7th
edition

2
Stereochemistry
 Some objects are not the
same as their mirror
images (technically, they
have no plane of
symmetry)
 A right-hand glove is
different than a left-
hand glove. The
property is commonly
called “handedness”
 Organic molecules
(including many drugs)
have handedness that
results from substitution
patterns on sp3
hybridized
carbon

3
Why this Chapter?
 Handedness is important in organic and
biochemistry
 Molecular handedness makes possible
specific interactions between enzymes and
substrates
 Stereochemistry looks at 3-D structures of
molecules

4
9.1 Enantiomers and the Tetrahedral
Carbon
 Enantiomers are molecules that are not the same as
their mirror image
 They are the “same” if the positions of the atoms can
coincide on a one-to-one basis (we test if they are
superimposable, which is imaginary)
 This is illustrated by enantiomers of lactic acid

5
Examples of Enantiomers
 Molecules that have one carbon with 4
different substituents have a
nonsuperimposable mirror image – enantiomer

6
9.2 The Reason for Handedness:
Chirality
 Molecules that are not superimposable with their
mirror images are chiral (have handedness)
 A plane of symmetry divides an entire molecule
into two pieces that are exact mirror images
 A molecule with a plane of symmetry is the same as
its mirror image and is said to be achiral

7
Chirality
 If an object has a plane of symmetry it is necessarily
the same as its mirror image
 The lack of a plane of symmetry is called
“handedness”, chirality
 Hands, gloves are prime examples of chiral object
 They have a “left” and a “right” version

8
Plane of Symmetry
 The plane has the same
thing on both sides for
the flask
 There is no mirror plane
for a hand

9
Chirality Centers
 A point in a molecule where four different groups (or
atoms) are attached to carbon is called a chirality center
 There are two nonsuperimposable ways that 4 different
different groups (or atoms) can be attached to one carbon
atom
 If two groups are the same, then there is only one way
 A chiral molecule usually has at least one chirality center

10
Chirality Centers in Chiral Molecules
 Groups are considered “different” if there is any
structural variation (if the groups could not be
superimposed if detached, they are different)
 In cyclic molecules, we compare by following in each
direction in a ring

11
9.3 Optical Activity
 Light restricted to pass through a plane is plane-
polarized
 Plane-polarized light that passes through solutions of
achiral compounds remains in that plane
 Solutions of chiral compounds rotate plane-polarized
light and the molecules are said to be optically active
 Phenomenon discovered by Jean-Baptiste Biot in the
early 19th
century

12
Optical Activity
 Light passes through a plane polarizer
 Plane polarized light is rotated in solutions of optically
active compounds
 Measured with polarimeter
 Rotation, in degrees, is []
 Clockwise rotation is called dextrorotatory
 Anti-clockwise is levorotatory

13
Measurement of Optical
Rotation
 A polarimeter measures the rotation of plane-
polarized that has passed through a solution
 The source passes through a polarizer and then is
detected at a second polarizer
 The angle between the entrance and exit planes is
the optical rotation.

14
Polarimetry
 Use monochromatic light, usually sodium D
 Movable polarizing filter to measure angle
 Clockwise = dextrorotatory = d or (+)
 Counterclockwise = levorotatory = l or (-)
 Not related to (R) and (S)
=>

15
Specific Rotation
 To have a basis for comparison, define specific
rotation, []D for an optically active compound
 []D = observed rotation/(pathlength x concentration)
= /(l x C) = degrees/(dm x g/mL)
 Specific rotation is that observed for 1 g/mL in
solution in cell with a 10 cm path using light from
sodium metal vapor (589 nm)

16
Specific Rotation and Molecules
 Characteristic property of a compound that is optically active – the
compound must be chiral
 The specific rotation of the enantiomer is equal in magnitude but
opposite in sign

17
9.5 Sequence Rules for
Specification of Configuration
 A general method applies to the configuration at each
chirality center (instead of to the whole molecule)
 The configuration is specified by the relative positions
of all the groups with respect to each other at the
chirality center
 The groups are ranked in an established priority
sequence and compared
 The relationship of the groups in priority order in
space determines the label applied to the
configuration, according to a rule

18
Sequence Rules (IUPAC)
Rule 1:
• Assign each group priority according to the Cahn
Ingold-Prelog scheme
• With the lowest priority group pointing away, look
at remaining 3 groups in a plane
• Clockwise is designated R (from Latin for “right”)
• Counterclockwise is designated S (from Latin word
for “left”)

19
Rule 2:
 If decision can’t be reached by ranking the first atoms
in the substituents, look at the second, third, or fourth
atoms until difference is found

20
Rule 3:
 Multiple-bonded atoms are equivalent to the same
number of single-bonded atoms

21
TEST STATS
AVERARE 34
MEDIAN 31
MODE 25
STD. DEV 17.25
LOW 0
HIGH 88
SCRIPTS 225

22
Br
OH
NH2
IDENTIFY STEREO/CHIRALITY CENTRES, IF ANY
OH
CH3
H
H3C
OH
ASSIGN R OR S CONFIGURATIONS TO EACH CHIRALITY CENTRE
Br Br O CH3

23
HBr
Br
+
Br
Br-
OH I
(2R,4R)-4-iodohexan-2-ol

24
9.6 Diastereomers
 Molecules with more than one chirality center have
mirror image stereoisomers that are enantiomers
 In addition they can have stereoisomeric forms that are
not mirror images, called diastereomers

26
9.7 Meso Compounds
 Tartaric acid has two chirality centers and two diastereomeric
forms
 One form is chiral and the other is achiral, but both have two
chirality centers
 An achiral compound with chirality centers is called a meso
compound – it has a plane of symmetry
 The two structures on the right in the figure are identical so the
compound (2R, 3S) is achiral

27
9.8 Racemic Mixtures and The
Resolution of Enantiomers
 A 50:50 mixture of two chiral compounds that are
mirror images does not rotate light – called a
racemic mixture (named for “racemic acid” that was
the double salt of (+) and (-) tartaric acid
 The pure compounds need to be separated or
resolved from the mixture (called a racemate)
 To separate components of a racemate (reversibly)
we make a derivative of each with a chiral substance
that is free of its enantiomer (resolving agent)
 This gives diastereomers that are separated by their
differing solubility
 The resolving agent is then removed

30
Fischer Projections
 Flat drawing that represents a 3D 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.

31
Fischer Rules
 Carbon chain is on the vertical line.
 Highest oxidized carbon at top.
 Rotation of 180 in plane doesn’t change
molecule.
 Do not rotate 90!
 Do not turn over out of plane! =>

32
Fischer Mirror Images
 Easy to draw, easy to find enantiomers, easy
to find internal mirror planes.
 Examples:
CH3
H Cl
Cl H
CH3
CH3
Cl H
H Cl
CH3
CH3
H Cl
H Cl
CH3
=>

33
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:
CH3
H Cl
Cl H
CH3
(S)
(S) =>

34
Diastereomers
 Stereoisomers that are not mirror images.
 Geometric isomers (cis-trans)
 Molecules with 2 or more chiral carbons.
=>

35
Alkenes
Cis-trans isomers are not mirror images, so
these are diastereomers.
C C
H H
CH3
H3C
cis-2-butene trans-2-butene
C C
H
H3C
CH3
H =>

36
Ring Compounds
 Cis-trans isomers possible.
 May also have enantiomers.
 Example: trans-1,3-dimethylcylohexane
CH3
H
H
CH3
CH3
H
H
CH3
=>

37
Two or More Chiral Carbons
 Enantiomer? Diastereomer? Meso? Assign (R) or
(S) to each chiral carbon.
 Enantiomers have opposite configurations at each
corresponding chiral carbon.
 Diastereomers have some matching, some opposite
configurations.
 Meso compounds have internal mirror plane.
 Maximum number is 2n
, where n = the number of
chiral carbons.
=>

38
Examples
COOH
H OH
HO H
COOH
(2R,3R)-tartaric acid
COOH
COOH
HO H
H OH
(2S,3S)-tartaric acid
=>
(2R,3S)-tartaric acid
COOH
COOH
H OH
H OH

39
9.9 A Review of Isomerism
 The flowchart summarizes the types of isomers we
have seen

40
Constitutional Isomers
 Different order of connections gives different carbon
backbone and/or different functional groups

41
Stereoisomers
 Same connections, different spatial arrangement of atoms
 Enantiomers (nonsuperimposable mirror images)
 Diastereomers (all other stereoisomers)
 Includes cis, trans and configurational

STEREOCHEMISTRY 1 for year 2 stdents.ppt

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