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
Positional Tautomers
Chain
isomers isomers
Stereoisomers
Configurational Conformers
isomers
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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.
H2C CH CH2 CH3
1-butene
H3C CH CH CH3
2-butene
H3C CH2 CH2 OH
H3C CH CH3
1-propanol
OH
2-propanol
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2) Positional isomers (2)
In cyclic compounds, the position isomerism is
characterized by different positions of
substituents in the cycle.
ortho-
meta-
R1
para-isomer
R1
R1
R2
R2
R2
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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
OH
HN
N
<<
HO
N
O
N
H
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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
H
H
H
H
H
H
H
C
H
H
C
H
H
H
H
H
H
Užstotoji arba sinperiplanarinė
konformacija
Emax
H
H
H
Sustabdytoji arba antiperiplanarinė
konformacija
Emin
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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
NH2
H
H
H
H
OH
H
NH2
OH
NH2
H
NH2
OH
H
H
H
HO
H
H
H
H
H
H
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H
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
O
O
*
CH3 CH
no stereocenter
C
OH
H 2N
*
CH
C
OH
CH2
OH
OH
Lactic acid
Serine
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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.
CHO
H
HO
OH group to the right
on bottom stereocenter
OH
H
H
OH
H
OH
CH2OH
D-glucose
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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.
CO2H
H2N
H
CO2H
H
NH2
CH2
CH2
SH
SH
L-Cysteine
D-Cysteine
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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 antinausea 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!
Clockwise (+)
Counterclockwise (-)
An equimolar solution of (+) and (-) enantiomers is
optically inactive, and () solution of enantiomers
is called racemic mixture or racemate.
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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
COOH
H
HO
enantiomers
COOH
COOH
COOH
NH2 H2N
H
H
NH2
H2N
H
H
OH
H
OH
HO
H
CH3
D(+)-threonine
H
CH3
CH3
L(-)-threonine
CH3
D(-)-allo-threonine L(+)-allo-threonine
diastereomers
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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).
CHO
H
HO
OH group to the right
on bottom stereocenter
OH
H
H
OH
H
OH
CH2OH
D-glucose
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Mesomers
D
L
Enantiomers
meso isomers
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.
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pi Diasteromers (cis/trans)
Br
Br
Br
Br
cis-2,3-Dibromo-but-2-ene
trans-2,3-Dibromo-but-2-ene
They occur when there is a restricted
rotation in a molecule.
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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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