Chapter 5Stereochemistry

Organic Chemistry

Chapter 5 2

Chirality• “Handedness”: right glove doesn’t fit the

left hand.• Mirror-image object is different from the

original object. =>

Chapter 5 3

Stereoisomers• Geometric isomers: cis-trans isomers.• Enantiomers: nonsuperimposable mirror

images, different molecules. =>

cis-1,2-dichlorocyclopentane trans -1,2-dichlorocyclopentane

H

ClH

ClH

ClH

ClH

ClCl

HH

ClCl

H

Chapter 5 4

Chiral Carbons• Tetrahedral carbons with 4 different

attached groups are chiral.• Its mirror image will be a different

compound (enantiomer). =>

Chapter 5 5

Mirror Planes of Symmetry• If two groups are

the same, carbon is achiral. (animation)

• A molecule with an internal mirror plane cannot be chiral.*

Caution! If there is no plane of symmetry, molecule may be chiral or achiral. See if mirror image can be superimposed. =>

Chapter 5 6

(R), (S) Nomenclature

• Different molecules (enantiomers) must have different names.

• Usually only one enantiomer will be biologically active.

• Configuration around the chiral carbon is specified with (R) and (S).

C

CO OH

H3C NH2H

natural alanine=>

Chapter 5 7

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. =>

Chapter 5 8

Assign Priorities

C

CO OH

H3C NH2H

natural alanine1

2

3 4

Cl

HCl

H*

12

34

12

3

4

=>

CC

O

H

CH CH2

CH2OHCH(CH3)2

* CC

C

CH2OHCH(CH3)2

H O

O

C

CH CH2

C

*expands to

Chapter 5 9

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)

=>

Chapter 5 10

Properties of Enantiomers• Same boiling point, melting point, density• Same refractive index• Different direction of rotation in polarimeter• Different interaction with other chiral

molecules – Enzymes– Taste buds, scent

=>

Chapter 5 11

Optical Activity• Rotation of plane-polarized light• Enantiomers rotate light in opposite directions,

but same number of degrees.

=>

Chapter 5 12

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)

=>

Chapter 5 13

Specific RotationObserved rotation depends on the length

of the cell and concentration, as well as the strength of optical activity, temperature, and wavelength of light.

[] = (observed) c l

c is concentration in g/mLl is length of path in decimeters. =>

Chapter 5 14

Calculate []D

• A 1.00-g sample is dissolved in 20.0 mL ethanol. 5.00 mL of this solution is placed in a 20.0-cm polarimeter tube at 25C. The observed rotation is 1.25 counterclockwise.

=>

Chapter 5 15

Biological Discrimination

=>

Chapter 5 16

Racemic Mixtures

• Equal quantities of d- and l- enantiomers.• Notation: (d,l) or ()• No optical activity.• The mixture may have different b.p. and m.p.

from the enantiomers!

=>

Chapter 5 17

Racemic ProductsIf optically inactive reagents combine to

form a chiral molecule, a racemic mixture of enantiomers is formed.

=>

Chapter 5 18

Optical Purity

• Also called enantiomeric excess.• Amount of pure enantiomer in excess of

the racemic mixture.• If o.p. = 50%, then the observed rotation

will be only 50% of the rotation of the pure enantiomer.

• Mixture composition would be 75-25. =>

Chapter 5 19

Calculate % Composition

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.

=>

Chapter 5 20

Chirality of Conformers

• If equilibrium exists between two chiral conformers, molecule is not chiral.

• Judge chirality by looking at the most symmetrical conformer.

• Cyclohexane can be considered to be planar, on average.

=>

Chapter 5 21

Mobile ConformersH

BrH

Br

H

BrH

Br

Nonsuperimposable mirror images,but equal energy and interconvertible.

BrBr

H H

Use planarapproximation.

=>

Chapter 5 22

Nonmobile ConformersIf the conformer is sterically hindered, it

may exist as enantiomers.

=>

Chapter 5 23

Allenes• Chiral compounds with no chiral carbon• Contains sp hybridized carbon with

adjacent double bonds: -C=C=C-• End carbons must have different groups.

Allene is achiral. =>

Chapter 5 24

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.

Chapter 5 25

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! =>

Chapter 5 26

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=>

Chapter 5 27

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) =>

Chapter 5 28

Diastereomers

• Stereoisomers that are not mirror images.• Geometric isomers (cis-trans)• Molecules with 2 or more chiral carbons.

=>

Chapter 5 29

Alkenes

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

C CH H

CH3H3Ccis-2-butene trans-2-butene

C CH

H3C

CH3

H =>

Chapter 5 30

Ring Compounds

• Cis-trans isomers possible.• May also have enantiomers.• Example: trans-1,3-dimethylcylohexane

CH3

H

H

CH3

CH3

H

H

CH3

=>

Chapter 5 31

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. =>

Chapter 5 32

ExamplesCOOH

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

Chapter 5 33

Fischer-Rosanoff Convention• 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, now know absolute configurations: D is (R) and L is (S).

• No relationship to dextro- or levorotatory. =>

Chapter 5 34

D and L AssignmentsCHO

H OH

CH2OH

D-(+)-glyceraldehyde

*CHO

H OH

HO H

H OH

H OH

CH2OHD-(+)-glucose

*

COOH

H2N H

CH2CH2COOH

L-(+)-glutamic acid

*=>

Chapter 5 35

Properties of Diastereomers• Diastereomers have different physical

properties: m.p., b.p.• They can be separated easily.• Enantiomers differ only in reaction with

other chiral molecules and the direction in which polarized light is rotated.

• Enantiomers are difficult to separate. =>

Chapter 5 36

Resolution of EnantiomersReact a racemic mixture with a chiral compound to

form diastereomers, which can be separated.

=>

Chapter 5 37

ChromatographicResolution of Enantiomers

=>

Chapter 5 38

End of Chapter 5