Вы находитесь на странице: 1из 23

1

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
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

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

2
Plane-Polarized Light

Plane-Polarized Light through an Achiral Compound

Plane-Polarized Light through a Chiral Compound

Polarimeter Measures Optical Rotation

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

3
Specific Rotation, []

Specific rotation, [] =
- observed rotation in degrees, C - concentration, g/mL, l - cell path length, dm
For example; (l)-(-)-2-butanol []D25 = -13.50
D D line of sodium as light source

OH
CH3CHCH2CH3

25 - temperature in degrees Celsius

Chiral Carbon

Dextrorotary designated as d or (+), clockwise rotation, Levorotary designated as l or (-),


counter-clockwise rotation
Racemic mixture: a mixture with equimolar amounts of the two enantiomers. This mixture
does not rotate polarized light because the two enantiomers cancel each other out.
Chirality: objects that are handed and are not superimposable are chiral objects. Your
hands are chiral objects. One way of testing for chirality is to examine the mirror image.
Chiral objects have mirror images different from the original.
Mirror images that can not be

Mirror images that can be superimposed

superimposed are chiral

are achiral (not chiral)

Molecules can be either chiral or achiral


H

Cl Cl

Cl Cl

Cl H

Cl H

Cl

mirror image
Superimposable mirror image achiral

Cl

mirror image
Non-Superimposable mirror image chiral

Enantiomers: Non-superimposable mirror images are called as enantiomers. Any chiral


molecule must have a corresponding mirror image enantiomer.
Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

4
Chiral Carbons
A carbon atom is chiral if it is bonded to four different groups. The carbon is often
referred to as an asymmetric or stereocenter.

H
CH3CH2

Br

Br

H
C CH3CH2

C
CH3

H3C

Are the above molecules superimposable? No, they are not! These molecules are therefore
chiral. Each represents an enantiomer.
The most common cause of chirality in molecules is the existence of a chiral carbon.
This is not the only cause, however!

If a molecule has only one chiral carbon, it is chiral

If a molecule has two or more chiral carbons, it may or may not be chiral

If a molecule has no chiral carbon, it may or may not be chiral.

Configurations
Relative configuration compares the arrangement of atoms in space of one compound
with those of another. Until the 1950s, all configurations were relative.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

5
Absolute configuration is the precise arrangement of atoms in space. We can now
determine the absolute configuration of almost any compound.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

6
Absolute configuration is the precise arrangement of atoms in space.
How do we define the arrangement of the 4 different groups around a chiral carbon?
In other words, how do we name the individual enantiomers of a molecule like the amino
acid alanine

CO2H
NH2
H3C

HO2C
H2N
C

C
H

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

CH3

7
Determination of Stereochemistry of Chiral Carbons in Fischer projections
First, rules for allowed motions when manipulating
1. A Fischer projection can never be removed from the plane of the paper.
2. 1800 rotation is allowed, 900 or 2700 rotations are not allowed.
3. Hold one group stationary; rotate others either clockwise or counter clockwise.
Violating any of these rules during manipulation will result in a change in stereochemistry of
the chiral carbon. The idea here is to manipulate without altering the stereochemistry.

Hold one group stationary and rotate the other three groups either clockwise or
counterclockwise.

Using an allowed motion, place the lowest priority group either on the top or the bottom of
the molecule. Then, look at the relationship of the other three groups
Clockwise R; Counterclockwise - S

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

10
Diastereomers: stereoisomers that are not enantiomers; they are not mirror images and they
are non-superimposable.
Diastereomers possess different physical properties, e.g. boiling point, melting point,
solubility, etc.
Enantiomers - possess identical physical properties.

Achiral molecule with two chiral carbons

Fischer-Rosanoff Convention (Relative)


Before 1951, only relative configurations could be known.
Sugars and amino acids with same relative configuration as (+)-glyceraldehyde were
assigned D and same as (-)-glyceraldehyde were assigned L.
With X-ray crystallography, we now know absolute configurations: D is (R) and L is (S).
No relationship to dextro- or levorotatory, meaning that some D enantiomers are (R) and
some are (S).
Anyone who can look at a structure and determine which way it will rotate polarized light
receives an automatic Noble Prize! There is a lot we do not know!

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

11

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!
If optically inactive reagents combine to form a chiral molecule, a racemic mixture is
formed.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

12
Optical Purity
Optical purity (o.p.) is sometimes called enantiomeric excess (e.e.).
One enantiomer is present in greater amounts

The specific rotation of (S)-2-iodobutane is +15.90. Determine the % composition of


a mixture of (R)- and (S)-2-iodobutane if the specific rotation of the mixture is -3.18.
Sign is from the enantiomer in excess: levorotatory

Three-Dimensional Representations
1.
2.
3.
4.

Flying Wedge Notation


Newman Projections
Sawhorse Projections
Fischer Projections

CH3

Br

Cl

CH3

CH3

Br

COOH

CH3

Br

HO

HO
H

H
OH

CH3

H3C

H
Br

CH2OH

There are four main types of representations for straight-chain molecules, as shown
above. From left to right, these structures are the Flying Wedge, the Newman Projection, the
Fisher Projection, and the Sawhorse Projection
Flying-Wedge or Wedge-Dash projection
The Flying-Wedge projection is the most common three-dimensional representation
of a three dimensional molecule on a two dimensional surface (paper). This kind of
representation is usually done for molecules containing chiral centre. In this representation,
the ordinary lines represent bonds in the plane of the paper. A solid Wedge (
a bond above the plane of the paper and a dashed wedge (

) represents

) or a broken line (

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

13
represents a bond below the plane of the paper. The Flying-Wedge projection formula of (R)
- Lactic acid, for example, can be shown as follows..
H3C
bonds in the plane
of the paper

bond bellow the plane of


the paper

OH
H3C

H
bond above the plane of
the paper

(R) - Lactic acid


Newman Projections
Newman Projections are used mainly for determining conformational relationships.
Recall that conformers are molecules that can be converted into one another by a rotation
around a single bond. Newman Projections are also useful when studying a reaction
involving prochiral molecules that have a double bond, in which the addition of a new group
creates a new stereocenter.
In this notation, you are actually viewing a molecule by looking down a particular
carbon-carbon bond. The front carbon of this bond is represented by a dot, and the back
carbon is represented by a large circle. The three remaining bonds are drawn as sticks coming
off the dot (or circle), separated by one another by 120 degrees. A Newman Projection can
be drawn such that the groups on the front carbon are staggered (60 degrees apart)
or eclipsed (directly overlapping) with the groups on the back carbon. Below are
two Newman Projections of ethane, C2H6. The structure on the left is staggered, and the
structure on the right is eclipsed. These are the simplest Newman Projections because they
have only two carbons, and all of the groups on both carbons are identical.
H

H
H

H
H

H
H

Staggered

Eclipsed

Adding

more

carbons

makes Newman

Projections more

complicated.

For

example, Newman Projections can be made for butane, such that its eclipsed, gauche,
and anti conformations can be seen. (Recall that these three forms of butane are
conformational isomers of one another).

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

14
In this case, the front dot represents the second carbon in the butane chain, and the
back

circle

represents

the

third

carbon

in

the

butane

chain.

The Newman

Projection condenses the bond between these two carbons.

CH3
CH3

CH3

CH3
H
H
H

CH3

H
H
CH3

Eclipsed

Staggered

Gauche

Sawhorse Projections
Sawhorse Projections are very similar to Newman Projections, but are used more
often because the carbon-carbon bond that is compressed in a Newman Projection is fully
drawn out in a Sawhorse Projection. When properly laid-out, Sawhorse Projections are
useful for determining enantiomeric or diasteromeric relationships between two molecules,
because the mirror image or superimposibility relationships are clearer.
Like with Newman Projections, a Sawhorse Projection is a view of a molecule down
a particular carbon-carbon bond, and groups connected to both the front and back carbons are
drawn using sticks at 120 degree angles. Sawhorse Projections can also be drawn so that the
groups on the front carbon are staggered (60 degrees apart) or eclipsed (directly overlapping)
with the groups on the back carbon. Below are two Sawhorse Projections of ethane. The
structure on the left is staggered, and the structure on the right is eclipsed. These are the
simplest Sawhorse Projections because they have only two carbons, and all of the groups on
the front and back carbons are identical.
H
H

H
H

H
H

H
H

Adding more carbons makes Sawhorse Projections slightly more complicated. As


with Newman Projections, Sawhorse Projections can be made for butane, such that
its eclipsed, gauche, and anti conformations can be seen. (Recall that these three forms of
butane are conformational isomers of one another.) Notice that is much easier to determine
the number of carbons in the longest chain using Sawhorse Projections than it is for

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

15
Newman Projections because the carbon-carbon bond between the second and third carbons
is drawn out.

H3C

H3C
H3C
H

H3C

H3C

CH3

Staggered

Gauch

Eclipsed

Fischer Projections
The Fischer projection, devised by Hermann Emil Fischer in 1891, is a twodimensional representation of a three-dimensional organic molecule by projection. Fischer
projections were originally proposed for the depiction of carbohydrates and used by chemists,
particularly in organic chemistry and biochemistry. The use of Fischer projections in noncarbohydrates are discouraged, as such drawings are ambiguous when confused with other
types of drawing.
CH3
OH

H
HO

HO

H
CH3

Fischer Projections are used often in drawing sugars and hydrocarbons, because the carbon
backbone is drawn as a straight vertical line, making them very easy to draw. When properly
laid-out, Fischer Projections are useful for determining enantiomeric or diasteromeric
relationships between two molecules, because the mirror image relationship is very clear.
In a Fischer Projection, each place where the horizontal and vertical lines cross
represents a carbon. The vertical lines are actually oriented away from you (similar
to dashes in the Wedge-Dash Notation) and the horizontal lines are oriented toward you
(similar to wedges in the Wedge-Dash Notation).
HO
Cl

Br

just copy this on ur page ......

CH3

HO

??

u will get the fischer projection

Cl
H3C

Br

that u see....
OH
Br

Cl
CH3

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

16
Resolution of Enantiomers
Enantiomers have the same physical properties so they can not be separated directly.
A possible technique for separation is chemical modification into diastereomers, which
possess different physical properties. Once in hand, diastereomers can be separated by
physical means, such as boiling point or recrystallization and then converted back into
enantiomers.
Two key requirements:
1. The reaction must be reversible so that the enantiomers can be released.
2. The reagent that reacts with the enantiomers must be stereochemically pure.
Example: The resolution of (S) and (R)-2-butanol via esterification with enantiomerically
pure (R,R)-tartaric acid
Key reaction: Esterification

Reaction Scheme

The initial product esters are diastereomers of each other and can be separated by
selective recrystallization (i.e. different solubilities in a solvent). The alcohols are recovered
by hydrolysis of the esters (reversible reaction).

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

17
Atropisomerism

The planar conformation of the biphenyl derivative is too sterically crowded. The
compound has no rotation around the central CC bond and thus it is
conformationally locked.
The staggered conformations are chiral: They are nonsuperimposable mirror images.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

18

Allenes can be Chiral

H
Cl

H
C

C
CH3

CH3

H
Cl

Penta-2,3-diene Is Chiral

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

19
Allenes possess cumulated double bonds, with the central carbon being sp hybridized.
This unique structure results in a perpendicular relationship of the two end CH2 groups of the
unsubstituted allene, shown below,

How Do I Recognize A Chiral Allene As Opposed To An Achiral Allene? [In other


words, an allene with a chiral axis vs. an allene without a chiral axis] You might ask, is there
some kind of short cut for recognizing a chiral allene? Sure. Examine both ends of the
allene. If either of those ends is attached to two identical substituents, it is achiral because
it will have a mirror plane.

ACHIRAL

Axial chirality refers to stereoisomerism resulting from the nonplanar arrangement of four
groups in pairs about a chiral axis.
Axial chirality is encountered in:
allenes
ortho-substituted biphenyls.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

20
Configurations of Axially Chiral Systems
The configurations in axially chiral systems are specified using Ra and Sa or P (plus)
and M (minus). The subscript a referring to axially chiral
Sequence Rules
The CIP priority rules are used to assign priority to the end groups, but with one
addition: That the near groups have a higher precedence over far groups. The two "near" and
two "far" substituents on the axial unit are ranked.
Viewing Rule
The chiral axis is viewed end-on and the sense of configuration determined.
The model below shows the side views and representations of the allene along the chiral axis.

To determine the sense of configuration, assign priority to the substituents on each of


the terminal carbons of the allene system (you may use a (higher priority) and b (lower
priority).

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

21
The sense of rotation is determined starting with the end of the allene that is closest,
then finishing with the end that is farthest. For the farthest end, only the group of higher
priority is considered.

Determining the Sense of Rotation (P vs M)


The sense of rotation is determined by looking only at the high priority substituents
starting with the end of the allene that is closest, then finishing with the end that is farthest. A
clockwise rotation is P (plus) and an anticlockwise rotation is M (minus).

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

22
Assigning Configurations of Atropisomers (Ra vs Sa)
By generating appropriate models of each atropisomer, the sense of configuration can
be determined.

Assigning Configurations of Atropisomers (P vs M)


By generating appropriate models of each atropisomer, the sense of configuration can
be determined.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur

23
Assignment
Determine the configurations of the following axially chiral systems using both the
Ra/Sa and P/M notations.

Prof. Dr. D. Ilangeswaran, M.Sc., M.Phil., Ph.D., RSGC., Thanjavur