Organic chemistry for medicine and biology students

Chem 2311Chapter 5

Stereochemistry

By Prof. Dr.Adel M. Awadallah

Islamic University of Gaza

StereochemistryIsomers: different compounds having the same molecular formula

CH3CH2OH CH3OCH3

ClI

Br

H

ICl

Br

HCH3 CH3CH3CH3

CH3

Et

Cl

Cl HH

CH3

Et

Cl

ClH

H

ClH

Cl H

ClH

H Cl

Cl H

ClH

Cl Cl

HH

IsomersDifferent compounds that have the same molecular formula

Constitutional isomers Stereoisomers

Atoms are attached to one another in different ways

Atoms have the same constitution but different arrangement in space

Enantiomers Diasteriomers

Non superimposable mirror- image stereoisomers

Non mirror-image stereoisomers

Conformational Configurational

Interconvertable by rotation

Interconvertable by bond breaking

SR

cis- trans-

cis trans

• A chiral molecule is one that is optically active

• A racemic mixture (racemic modification) is one with equal ratios of enantiomers (50:50 mixture)

Configuration and the R-S Convention

Examples

BrI

Cl

H

BrCl

CH3

H

CH3Et

H

F

CH3

H

OH

O

CH3

CH2CH3

H

CH3CH2

HI

Cl

Br

BrH

CH3

Et

HEt

CH3

F

H

OH

CH3

O

CH3

CH3

CH2OH

CH2CH3CH2

R S R S S

S R R R S

Compounds with more than one stereogenic center; (Diasteriomers)

CH3

Et

H

Cl

Cl

H

CH3

Et

Cl

H

H

Cl

CH3

Et

H

H

Cl

Cl

CH3

Et

Cl

Cl

H

H

1

2

3

(2R,3R) (2S,3S) (2R,3S) (2S,3R)

1 2 3 4

1 and 2 are enantiomers, 3 and 4 are also enantiomers

1 and 3 , 1 and 4, 2 and 3, 2 and 4 are diastereomers

Diastereomers are non mirror image stereoisomers

If a molecule has n different stereogenic centers, it may exist in a maximum of 2n stereisomeric forms. There will be a maximum of 2n / 2pairs of enantiomers.in the above case 2 stereogenic centers, 2 pairs of enantiomers, 4 stereoisomers

CH3

CH3

H

Cl

Cl

H

CH3

CH3

Cl

H

H

Cl

CH3

CH3

H

H

Cl

Cl

CH3

CH3

Cl

Cl

H

H

1

2

3

(2R,3R) (2S,3S) (2R,3S) (2S,3R)

1 2 3 4

1 and 2 are enantiomers, 3 and 4 are the same compound (Meso structure)

1 and 3 , 2 and 3, are diastereomers

Diastereomers are non mirror image stereoisomers

A meso compound: is an achiral ( optically inactive) diastereomer of a compound with stereogenic centers. Its stereogenic centers have opposite configurations.One half of the molecule is the mirror image of the other half

1 pair of enantiomers and a total of 3 isomers

same compound

CH3Cl

Br

H

HCl

CH3

Br

CH3Cl

H

H

BrCH3

CH3H

Cl

Br

HCH3

CH3Cl

H

H

BrCH3

HCH3

Cl

H

BrCH3

CH3Cl

H

H

BrCH3

HCH3

Cl

Br

HCH3

ExampleWhat is the relation between the following compounds

R R

same compound

1

2

3 4

(2S,3S) (2R,3S)

Diastereomers

(2S,3S) (2R,3R)

Enantiomers

(2S,3S) (2S,3S)

Same compound

• Properties of enantiomers and diastereomers• A) Enantiomers• Have the same physical properties except for

direction of rotation of plane polarized light• Have the same chemical properties except for

their reaction with other chiral molecules• (This usually seen in their biological activity)• B) Diastereomers• Have different physical properties• Similar chemical properties

• Chemical reactions of stereoisomers• 1) Generation of a chiral center

CH3

CH2Ch3

HH

CH3

H CH2CH3

CH3

CH2Ch3

HCl

CH3

CH2Ch3

ClHCl2

CH3

Et

BrH

CH3

Et

HBrEt

CH3H

heat

.

planar radicalequal ratios

Cl2 2Cl.

Cl.

-HCl

HBr +

planar carbocation equal ratios

Br -

Reaction away from a chiral center

CH3

CH2Ch3

H COOH

EtOH / acid CH3

CH2Ch3

H COOEt

CH2

CH2Ch3

H Cl

OH

CH2Ch3

H Cl

OH

retention of configuration

retention of configuration

KMnO4

Generation of a second chiral center

CH3

ClH

CH3

CH3

Cl

H

H

Br

CH3

CH3

Cl

Br

H

H

HBr+

Diastereomeric products at different rates and in unequal amounts

Resolution of enantiomers

• Enantiomers + chiral molecules gives diasteriomers which can be sepearated, then we get red of the chiral molecules