Isomers The compounds that have identical molecular

formulas but different arrangement of atoms and

properties.

Constitutional isomers (structural isomers).

C5H10

Stereoisomers – the same molecular formulas but

different arrangement of atoms in space.

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Isomers

Constitutional

(structural)

isomers

Chain

isomers

Positional

isomers Tautomers

Stereoisomers

Configurational

isomers Conformers

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I. Constitutional isomers

The compounds that have identical molecular

formulas but different connectivity of atoms

and properties:

1) Chain isomers.

2) Positional isomers.

3) Tautomers.

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1) Chain isomers

Differ in various forms of chains

(linear and branched) and

cycles.

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2) Positional isomers (1)

Differ in position of heteroatoms, functional groups or unsaturated bonds in the molecule.

CH

2CH CH

2CH

3CH

3CH CH CH

3

CH3

CH2

CH2

OH CH3

CH CH3

OH

1-butene 2-butene

1-propanol 2-propanol

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2) Positional isomers (2)

R1

R2

R1

R2

R1

R2

In cyclic compounds, the position isomerism is characterized by different positions of substituents in the cycle.

ortho- meta- para-isomer

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3) Tautomers

Tautomerism - chemical isomerism characterized by

relatively easy interconversion of isomeric forms in

equilibrium.

Tautomers - organic compounds that are

interconvertible.

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Forms of tautomerism (1)

Prototropic tautomerism - shift of

the proton from one atom to the

another atom.

O

O

NH

NH

OH

OH

N

N

<<

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Forms of tautomerism (2)

Ring-chain tautomerism - the movement of

the proton is accompanied by a change from

an open structure to a ring.

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II. Stereoisomers

The compounds that have identical molecular

formulas and same connectivity of atoms but

different arrangement of atoms in space:

1) Conformational isomers (conformers).

2) Configurational isomers:

Enantiomers.

Diastereomers.

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Conformation and configuration

Changing the conformation of a molecule means

rotating about bonds, but not breaking them.

Changing the configuration of a molecule always

means that bonds are broken.

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Conformations

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1) Conformational isomers

Linear alkane conformations.

Cyclohexane conformations.

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Newman projections

Užstotoji arba sinperiplanarinėkonformacija

Emax

Sustabdytoji arba antiperiplanarinėkonformacija

Emin

H

HH

H

H

H

H

HH

H

H H

C C

H

HH

H

H

H

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Linear conformational isomers (1)

Isomers resulting from the free rotation of a single

bond.

Staggered conformation - this conformation is

favoured.

Ethane: CH3-CH3

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Linear conformational isomers (2)

Eclipsed conformation.

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Linear conformational isomers (3)

HO-CH2-CH2-NH2

H

OH

H H

NH2

H

H

H H

NH2

HO

HH H

NH2

H

OH

H

H

H H

NH2

H

OH

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Stereoisomers

Enantiomers and diastereomers

They affect the plane of polarised light.

Enantiomers are non-superimposable mirror

images.

Enantiomers occur only with those compounds,

which are chiral.

Diastereomers are stereoisomers that are not

mirror images of each other.

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Chirality (1)

The word chiral comes from the Greek word meaning ‘hand’.

It is used to describe an object that is non-superimposable on its mirror image.

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Chirality (2)

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Chirality (3)

The mirror images of chiral compounds can

not be superimposed.

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Achiral structures

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Chiral and achiral molecules

The essential difference between the two molecules lies in their symmetry:

If there are two groups the same attached to the central carbon atom, the molecule has a plane of symmetry – achiral molecule.

Where there are four different groups attached, there is no symmetry anywhere in the molecule – chiral molecule.

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Asymmetric center (Chiral center)

The carbon atom with the four different groups

attached, which causes the lack of symmetry is

a chiral centre (asymmetric carbon atom).

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Locating a stereocenter

CH3 CH C

OH

OH

O

Lactic acid

*

Serine

no stereocenter H2N CH C

CH2

OH

O

OH

*

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Enantiomers

A pair of enantiomers is always possible for

molecules that contain one tetrahedral atom

with four different groups attached to it.

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Drawing Fischer projections Place the most oxidized group at the top.

Use vertical lines in place of dashes for bonds that go back.

Use horizontal line in place of wedges for bonds that come

forward.

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D- and L- configuration

By convention, the letter L is assigned to the

structure with the -OH (or NH2) in the left.

The letter D is assigned to the structure with the -

OH (or NH2) on the right.

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D and L compounds: carbohydrates

Natural sugars have the D configuration

(L sugars are rare in nature).

Often drawn as Fischer projections with most oxidized carbon at top.

H

CHO

OH

HHO

OHH

OHH

CH2OH

D-glucose

OH group to the righton bottom stereocenter

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D and L compounds: amino acids

Natural amino acids have the L configuration.

Often drawn as Fischer projections with carboxyl

group at the top.

Since enzymes are proteins, they are inherently

chiral, and can differentiate enantiomeric

substrates.

H2N

CH2

SH

CO2H

H

L-Cysteine

H

CH2

SH

CO2H

NH2

D-Cysteine30

Importance of enantiomerism

Enantiomers react in a different way with

other compounds:

the configuration of an isomer should

correspond to a configuration of assymetric

atom of another compound in a way how a

key fit into a lock.

Otherwise interaction is impossible.

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The danger of (S)-thalidomide (R and S configuration)

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Thalidomide birth defects

• Thalidomide is an anti-

nausea and sedative drug

that was introduced in the

late 1950s to be used as a

sleeping pill and was quickly

discovered to help pregnant

women with the effects of

morning sickness] It was sold

from 1957 until 1962, when it

was withdrawn after being

found to be a teratogen,

which caused many different

forms of birth defects

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Optical characteristics of

enantiomers

Enantiomers are optical isomers.

They could rotate polarized light

clockwise (+) or counterclockwise (-)

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Polarization of light

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Optical activity

Chiral molecules rotate polarised light!

An equimolar solution of (+) and (-) enantiomers is optically inactive, and () solution of enantiomers is called racemic mixture or racemate.

Clockwise (+) Counterclockwise (-)

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Diastereomers

Non-mirror image stereoisomers, and have

opposite configurations at one or more of the

chiral centers.

If two compounds are stereoisomers but they are

not enantiomers, then they are diastereomers:

– have different physical properties and

reactivity.

– can be separated by ordinary physical

methods.

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2-amino-3-hydroxybutanoic acid

(threonine)

enantiomers enantiomers

diastereomers

H NH2

OH H

CH3

COOH

NH2

H

H OH

CH3

COOH

H NH2

H OH

CH3

COOH

NH2

H

OH H

CH3

COOH

D(+)-threonine L(-)-threonine D(-)-allo-threonine L(+)-allo-threonine

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How many stereoisomers are

possible?

Number of stereoisomers = 2n, where n = number of

chiral atoms in the molecule.

There are 4 chiral atoms in the molecule of glucose

Consequently, there are 8 pairs of enantiomers

(16 isomers).

H

CHO

OH

HHO

OHH

OHH

CH2OH

D-glucose

OH group to the righton bottom stereocenter

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meso isomers Enantiomers

Formulas of enantiomers represent non superimposable mirror image

isomers.

Meso isomers are also mirror images. But by turning one of them 180°

it is exactly superimposable on another one.Therefore these meso

forms represent the same compound. A plane of symmetry can be

passed between carbons 2 and 3 so that the top and bottom halves of

the molecule are mirror images.

D L

Mesomers

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pi Diasteromers (cis/trans)

They occur when there is a restricted

rotation in a molecule.

Br

Br

Br Br

cis-2,3-Dibromo-but-2-ene trans-2,3-Dibromo-but-2-ene

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Example of isomerisation

Maleic (cis-butenedioic) acid and fumaric acid are pi diasteromers.

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Example of stereospecificity

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