Let’s consider some molecules……First

H

pair

Brsame molecular formula (CH2BrCl)

same atom connectivity

superposableHBr

A

HCl

Cl H

B

Second

H

pairsame molecular formula

same atom connectivity

nonsuperposable

(CHFBrCl)F

F Br

HBr

Cl Cl

C D

3

stereoisomers(two different compounds)

identical (same compound)

Thus, we can define………

Stereoisomers: isomersthat have

same formula and connectivity but differ in

the position of the atoms in space

Stereochemistry: chemistry that

studies the properties of stereoisomers

4

Stereochemistry is a Greek word in which ‘stereos’ means solid.

Stereochemistry deals with the spatial arrangements of atoms and groups in a

molecule.

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.

Stereochemistry includes methods for determining and describing the

relationships of atoms within molecules; The effect these relationships on the

physical or biological properties of the molecules. The manner in which these

relationships influence the reactivity of the molecules (dynamic

stereochemistry).

Isomers

Compounds with the

same molecular formula

Conformational

Isome rs

rotation about

single bonds

with chiral centers

Stereoisomers

Meso

Compounds

Enantiomers

Constitutional

Isome rs

Cis,Trans

(E,Z) Isome rs

(can be called

diastereomers)

Conformations

rotation

re stricted

different

connectivity

Diaste reomers

stereocenters

but no chiral centers

Enantiomers

one chiral centerm ore than

one chiral center

chiralachiral

not mirror

images

mirror

images

Atropisomers

same

connectivity

Isomers types1. Constitutional : isomers differ in the order in which the atoms are connected so

they can contain different functional groups and / or bonding patterns (e.g. branching) example: 1-propanol, 2-propanol and ethyl methyl ether (C3H8O)

2. Conformational isomers

stereoisomers that are produced by rotation about σ bond( single bond) , and are often rapidly interconverted at room temperature

Example :

• Conformational isomers are interconvertible by rotations about singlebonds, and the conformation of a molecule concerns features related torotations about single bonds

• A related term is atropisomers, which are stereoisomers that can beinterconverted by rotation about single bonds but for which the barrierto rotation is large enough that the stereoisomers can be separated anddo not interconvert readily at room temperature.

• Atropisomerism is that kind of isomerism, where the conformers

(called atropisomers) can be isolated as separate chemical species

and which arise from restricted rotation about a single bond.

OPTICAL ISOMERISM

Occurrence another form of stereoisomerism

occurs when compounds have non-superimposable mirror images

Isomers the two different forms are known as optical isomers or enantiomers

they occur when molecules have a chiral centre

a chiral centre contains an asymmetric carbon atom

an asymmetric carbon has four different atoms (or groups)

arranged tetrahedrally around it.

OPTICAL ISOMERISM

Occurrence another form of stereoisomerism

occurs when compounds have non-superimposable mirror images

Isomers the two different forms are known as optical isomers or enantiomers

they occur when molecules have a chiral centre

a chiral centre contains an asymmetric carbon atom

an asymmetric carbon has four different atoms (or groups)

arranged tetrahedrally around it.

There are four different colours

arranged tetrahedrally about th

e carbon atom

2-chlorobutane exhibits optical isomerism

because the second carbon atom has four

different atoms/groups attached

CHIRAL CENTRES

A chiral object is that which has non superimposable mirror image.

Chiral Center

An atom with four different groups attached

to it, is called chiral atom and also called

chiral center.

Chirality

Any object that has a plane or point of symmetry is achiral

(not chiral). e.g. 2-chloropropane

An atom with four different groups are not attached to it, is

called achiral atom.

Achiral

Enantiomers are stereoisomers that are non-superimposable on

their mirror images.

Enantiomers

Enantiomers

Enantiomers are that isomers, which are mirror image of each other, i.e.

they are not super imposable.

Enantiomers have identical physical and chemical properties, except in two

important respects-

1. They rotate the plane of polarized light in opposite direction, though in

equal amounts. The isomers which rotates the plane to the left (counter

clockwise) is called the Levo isomer and designated as (-), while the one

which rotates the plane to the right (clockwise) is called dextro isomer and

is designated as (+).

2. They react at different rates with other optically active compounds. It is

for this reason that many compounds are biologically active while their

enantiomers are not.

Meso compoundsMeso compounds

A meso compound is one whose molecules are super-imposable

on their mirror images even though they contain chiral centres.

Diastereomers are stereoisomers that are not mirror images of

each other – they are stereoisomers that are not enantiomers.

Diastereomers

Diastereoisomers rotate the plane of polarization by different amount and

are not identical in configuration and are not mirror images of each other.

Diastereoisomers differ in physical properties such as melting point,

density, solubility, refractive index etc.

Enanatiomers

“Optical isomer”

Same carbon

Same connection

Are mirror image

Nonsuperimposable

All configurations

are opposite

Diastereomers

Same carbon

Same connection

Are Not mirror image

Nonsuperimposable

Not All configurations

are opposite

Chiral

Enantiomers are chiral: Chiral:

Not superimposable on its mirror image

Many natural and man-made objects are chiral: hands scissors screws (left-handed vs. right-handed threads)

Right hand threads slope up to the right.

Chiral

Some molecules are chiral:

Asymmetric

(chiral) carbon

Asymmetric Carbons

The most common feature that leads to chirality in organic compounds is the presence of an asymmetric (or chiral) carbon atom. A carbon atom that is bonded to four different

groups

In general: no asymmetric C usually achiral 1 asymmetric C always chiral > 2 asymmetric C may or may not be

chiral

Asymmetric Carbons

Example: Identify all asymmetric carbons present in the following compounds.

C C C C

OH

H

H

H

H

H

H H

H

H H3C

CH3CH2CH3

H H H

BrBr

Br CH3

Br

H

Achiral

Many molecules and objects are achiral: identical to its mirror image not chiral

H H

ClCl

H H

ClCl

Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane contains two asymmetric carbons but is achiral. contains an internal mirror plane of symmetry

Any molecule that has an internal mirror plane of symmetry is achiral even if it contains asymmetric carbon atoms.

H H

ClCl

s

Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane is a mesocompound: an achiral compound that contains chiral centers

often contains an internal mirror plane of symmetry

Internal Plane of Symmetry

Example: Which of the following compounds contain an internal mirror plane of symmetry?

C

C

C

C

C

C

O

OH

O

OH

HO

OH

H

H

H

ClHF

C C

CO2H

HOH

HHO

HO2C

C C

CO2H

OHH

HHO

HO2C

CH3H

H3C H

FF

C C

CH2CH3

BrH

BrH

H3CH2C

Chiral vs. Achiral To determine if a compound is chiral:

0 asymmetric carbons: Usually achiral 1 asymmetric carbon: Always chiral 2 asymmetric carbons: Chiral or achiral

Does the compound have an internal plane of symmetry?– Yes: achiral– No:

– If mirror image is non-superimposable, then it’s chiral.

– If mirror image is superimposable, then it’s achiral.

Conformationally Mobile Systems

Alkanes and cycloalkanes are conformationally mobile. rapidly converting from one conformation to another

In order to determine whether a cycloalkane is chiral, draw its most symmetrical conformation (a flat ring).

Chiral vs. Achiral

Example: Identify the following molecules as chiral or achiral.

CH3 C CH

2CH

3

CH3

Cl

H H

BrBr

BrH

Br H

CH3 C CH

2CH

3

CH3

Cl

H H

BrBr

BrH

Br H

CH3CCH2CH3

CH3

Cl

CH3CHCH2CH2CH3

ClC C

Br

BrH

HCH3CH2

CH2CH3

trans-1,3-dibromocyclohexane

ethylcyclohexane

Mirror Planes of Symmetry If two groups are the

same, carbon is

achiral. (animation)

A molecule with an

internal mirror plane

cannot be chiral.*

Notes ! If there is no plane of symmetry, molecule may be

chiral or achiral. See if mirror image can be superimposed.

=>

Chiral molecules does Not

contain a plane of symmatry σ

Symmetry tests for achiral structures

Any molecule with a plane of symmetryor a center

of symmetry must be achiral.Achiral center: a C atom is attached by 2 or more same groups. ---------------------------------------------------------------------Chiral

Non-superimposable

with its mirror image

asymmetric carbon

4 different attached

groups

Enanatiomers

achiral

Superimposable

with its mirror image

plane of symmetry

2 or more same attach

groups.

not enantiomers

Light that has been passed through a nicol prism or other

polarizing medium so that all of the vibrations are in the same

plane.

plane polarized light

non-polarized polarized

OPTICAL ISOMERISMThe polarimeter

If the light appears to have turned to the right turned to the left

DEXTROROTATORY LAEVOROTATORY

A Light source produces light vibrating in all directions

B Polarising filter only allows through light vibrating in one direction

C Plane polarised light passes through sample

D If substance is optically active it rotates the plane polarised light

E Analysing filter is turned so that light reaches a maximum

F Direction of rotation is measured coming towards the observer

A B

C DE

F

Polarimeter

It is used to measure thr optical activity of a compund.

Specific RotationThe angle of rotation of plane polarized ligh

t by a 1.00 gram per cm-3 sample in a 1 dm tube. [α ]D (D = sodium lamp, λ = 589 mμ).

α[ α ]D = where α = observed rotation

l * dl = length (dm)

d = concentration (g/cc)

(+)-alanine [ α ]D = +8.5

(-)-lactic acid [α ]D = -3.8

DefinitionsOptically Activity: the ability of compounds to rotate the

plane polarized light towards left or right.

Dextrorotatory (d) or (+).: an optically active compound

that rotates plane polarized light in a clockwisedirection.

Levorotatory (l) or (-): an optically active compound

that rotates plane polarized light in a

counterclockwise direction.

H

N

H

(-)-Nicotine CH3NH3CCH3 H

(+)-MethamphetamineN

8

Summary

Stereoisomers: isomers that have same formula and connectivity but

differ in the position of the atoms in space. They possess one or mor

e

stereocenters

Stereocenter: a carbon atom bearing 4 different atoms or group of

atoms.

Chiral: any moleculethat is nonsuperposable with its mirror image.

Enantiomers: stereoisomers that are non superposable mirror

images

Racemic mixture: a 1:1 (equimolar) mixture of two enantiomers.

Optically Active: the ability of some compounds to rotate plane polariz

ed light.

Biological Significance of ChiralitySince most of the natural (biological) environment consists of enantiomeric mol

ecules (amino acids, nucleosides, carbohydrates and phospholipids are chiral mo

lecules), then enantiomers will display different properties. Then, in our body

Drug

Enzyme

32

Weak BindingTight Binding

Enantiomers

Biological Significance of ChiralityEnantiomers

OH

of EpinephrineH3C H3C HH N H N

OH OHH HR SH HO

Anionic Flat areasite

OccupiedNot Occupied

Poorer Fit LessActive Better Fit More Active

33

(-)-Epinephrine(+)-Epinephrine

Flat areaAnionic

site

OH OH

Enzyme

Stereochemistry and Drug Action

Why do chiral molecules react differently with biological molecules?

A A A B

C B C A

A’ A’ A’ B’

C’ B’ C’ A’

R S