Stereochemistry

25 April 2022
20:54

STEREOCHEMISTRY
Static and Dynamic structural
representation of molecule in three
dimensional space.

CONFORMATION
Conformation of a molecule are three
dimensional arrangements that differ
only by rotation around the single bond
(σ - bond). The atoms remain connected
in same order as before. There is no
bond making of bond breaking in the
process of conformational changes.

STEREOISOMERS V/S
CONSTITUTIONAL
Stereoisomers and constitutional
isomers. Isomers are compounds that
contain the same atoms bonded
together in different ways. If the
connectivity of the atoms in the two
isomers is different, they are
constitutional isomers. If the
connectivity of the atoms in the two
isomers is the same, they are
stereoisomers. Enantiomers are
stereoisomers, and so are E and Z
double bonds.

ENANTIOMERS AND CHIRALITY

Enantiomers are the isomers that are
not identical but are mirror images of
one another.

Chiral molecules are the molecules

whose mirror images are non-super
imposable on one another.
Achiral molecules are mirror-image
molecules which are super-imposable on
one another.

Steps to know Chirality of molecules:

 Draw the mirror image of the

molecule in question
 Flip the mirror image molecule by

180˚
  Impose the molecule on the original
molecule
Result:
 If non-super imposable: Chiral

 If super-imposable: Achiral

PLANE OF 'SYMMETRY' AND

CHIRALITY
 A structure with a plane of
symmetry is achiral and
superimposable on its mirror
image and cannot exist as two
enantiomers.
 A structure without a plane of
symmetry is chiral and not
superimposable on its mirror
image and can exist as two
enantiomers.

STEREOGENIC OR CHIRAL CENTRE

A tetrahedral carbon atom which has
four different group of atoms around it
and thus doesn’t have a plane of
symmetry is called a stereogenic
centre. Optical activity is the property
of the chiral centre carbon.
R & S CONFIGURATION
ASSINGNMENT
 Assign a priority number (1–4) to
each substituent at the chiral centre.
Atoms with higher atomic numbers
get higher priority.

Atomic number
 Nitrogen - 7 Out of
CO2H and CH3, the first is bulkier as it
 Carbon - 6 has
oxygen(atomic number 6) while the
latter has
 Hydrogen - 1 only
hydrogen, so CO2H gets priority over
CH3.
  Arrange the molecule so that the
lowest priority substituent is pointing
away from you.

 Mentally move from substituent

priority 1 to 2 to 3. If you are moving
in a clockwise manner, assign the
label R to the chiral centre; if you
are moving in an anticlockwise
manner, assign the label S to the
chiral centre

OPTICAL ACTIVITY
  The rotation of plane-polarized light
by a molecule is known as optical
activity.
 Observation of the rotation of plane-
polarized light is known as
polarimetry.
 Plane-polarized light can be
considered as a beam of light in
which all of the light waves have
their direction of vibration
aligned parallel. It is produced by
shining light through a polarizing
filter.

FACTORS ON WHICH ANGLE ROTATION

OF PLANE POLARIZED LIGHT BY A
COMPOUND DEPEND:
  Path length (how far the light has to
pass through the solution, in dm)
 Concentration (g cm-3)
 Temperature
 Solvent (ethanol and chloroform)
 Wavelength (589 nm, yellow light)

OPTICAL ROTATION AND

SPECIFIC ROTATION
 Optical rotation is the rotation of
plane-polarized light when a light
beam is directed through certain
materials.
 Specific rotation gives the angle of
rotation of plane-polarized light by a
certain compound at a certain
temperature.
 Specific rotation is an intensive
property.
[α]=α/(c*l)

α - optical rotation
c - concentration of compound used
l - lenght of the polarimeter tube
A simple acid, known as mandelic acid, can be
obtained from almonds in an enantiomerically
pure form. When 28 mg was dissolved in 1 cm3 of
ethanol and the solution placed in a 10-cm-long
polarimeter cell, an optical rotation α of –4.35°
was measured (that is, 4.35° to the left) at 20 °C
with light of wavelength 589 nm. What is the
specific rotation of the acid?

First, we need to convert the concentration to

grammes per cubic centimetre: 28 mg in 1 cm3 is
the same as 0.028 g cm-3 . The path length of 10
cm is 1 dm, so

 Dextrorotatory: Enantiomer that

turns the plane-polarized light to
right. Denoted by (+) sign.
 Laevorotatory: Enantiomer that turns
the plane polarized light to left.
Denoted by(-) sign.
 The direction in which light is rotated
is not dependent on whether a
stereogenic centre is R or S.

D and L CONFIGURATION
Any enantiomerically pure compound
that could be related, by a series of
chemical degradations and
transformations, to D-(+)-
glyceraldehyde was labelled D, and
any compound that could be related to
L-(–)-glyceraldehyde was labelled L.

Remember that the R/S, +/–, and D/L

nomenclatures all arise from different
observations and the fact that a
molecule has, say, the R configuration
gives no clue as to whether it will have
+ or – optical activity or be labelled D or
L. Never try and label a molecule as D/L
or +/– simply by working it out from the
structure. Likewise, never try and
predict whether a molecule will have a
+ or – specific rotation by looking at the
structure.

DIASTEREOMERS
Stereoisomers that are not
enantiomers (i.e. do not share mirror
object relation) but are non-
superimposable. The physical and
chemical properties of diastereomers
are different unlike enantiomers.
CHIRALITY OF DIASTEREOMERS

Diastereomers can be chiral or
achiral .

Look for plane of symmetry in
the molecule.

If the molecule contain plane of
symmetry then it is achiral.


If it does not contain plane of
symmetry, the it is chiral.
 ENATIOMERS OF
DIASTEREOMERS

When you are considering the

stereochemistry of a compound, follow
the order:
 Diastereomers (I)
  Enantiomers (II)

Though diastereomers are easy to

separate, to separate the enantiomers
of the diastereomer is very difficult. The
physical and chemical properties of
enantio-
mers are identical; the physical and
chemical properties of diastereoisomers
differ.

ABSOLUTE AND RELATIVE

STEREOCHEMISTRY
 Absolute configuration refers to
the actual or exact arrangement
of atoms or groups of atoms in a
molecule. The absolute
configuration at a chiral centre
in a molecule is a time-
independent and unambiguous
symbolic descri-ption of the
spatial arrangement of ligands
(groups) bonded to the chiral
centre.
 Relative configuration refers to
the relationship between two
 stereoisomers. The relative
configuration is the
experimentally determined
relationship between two
enantiomers even though we
may not know the absolute
configuration.
 Enantiomers are stereoisomers that
are mirror images. A pair of
enantiomers are mirror-image forms
of the same compound and have
opposite absolute
stereochemistry.
 Diastereoisomers are stereoisomers
that are not mirror images. Two
diastereoisomers are different
compounds, and have different
relative stereochemistry.
 Diastereoisomers may be achiral
(have a plane of symmetry) or they
may be chiral (have no plane of
symmetry)
DIASTEREOMERS WITH MORE
THAN ONE STEREOGENIC CENTRE
Diastereoisomers can arise when
structures have more than one
stereogenic centre

Converting enantiomers and

diastereoisomers
• To go from one enantiomer to another,
both stereogenic centres are inverted.
• To go from one diastereoisomer to
another, only one of the two is inverted.
A structure with n stereogenic centres
can exist as 2n stereoisomers. These
stereoisomers consist of 2n-1
diastereoisomers, each of which has a
pair of enantiomers.
REMEMBER:
 This formula works for non-

symmetrical molecules that are

chiral.
 Always revisit the structures

after drawing them, and look for

similar by rotating in head the
molecules only to eliminate one.
(Mesomers)
FOR SUGARS
 The number of carbon atoms, n, can

be 3–8: aldoses have n – 2

stereogenic centres and ketoses n –
3 stereogenic centres.

MESOMERS
 (1R,2S)-Tartaric acid and (1S,2R)-
tartaric acid are not enantiomers, but
they are identical because, even
though they contain stereogenic
centres, they are achiral. It has plane
of symmetry therefore this
diastereomers of tartaric acid is not
chiral.
 Compounds that contain stereogenic
centres but are themselves achiral
are called meso compounds. This
means that there is a plane of
symmetry with R stereochemistry on
 one side and S stereochemistry on
the other.

HOW TO WORK OUT

STEREOCHEMISTRY OF A
MOLECULE
 Draw the compound with the carbon
skeleton in the usual zig-zag fashion
running across the page.
 Identify the chiral centres.

 Decide how many diastereoisomers

there are by putting the substituents
at those centres up or down. It often
helps to give each diastereoisomer a
‘tag’ name. In this case there are
three diastereoisomers. The three
OH groups can be all on the same
side or else one of the end OHs or
the middle one can be on the
opposite side to the rest. We can call
 the first syn, syn because the two
pairs of chiral centres (1 & 2, and 2 &
3) groups are both arranged with the
OHs on the same side of the
molecule (syn)
 By checking on possible planes of
symmetry, see which
diastereoisomers are chiral. In this
case only the plane down the centre
can be a plane of symmetry.

 Draw the enantiomers of any chiral

diastereoisomer by inverting all the
stereogenic centres.

 Announce the conclusion. You could

have said that there are four
 ‘stereoisomers’ but the following
statement is much more helpful.
There are three diastereoisomers,
the syn,syn, the syn,anti, and the
anti,anti. The syn,syn and the
anti,anti are achiral (meso)
compounds but the syn,anti is chiral
and has two enantiomers.

ATROPISOMERS AND SPIRO

COMPOUNDS
 Compounds that are chiral because
of restricted rotation about a single
bond are called atropisomers (from
the Greek for ‘won’t turn’)

 In BINAP, two rings have to be

orthogonal because of the
 tetrahedral nature of the central
carbon atom.
 The second, allene example rely on
the rigidity of π systems but this
simple saturated system is also
chiral.

 Cyclic compounds with no chiral

centre but no plane of symmetry
with rings joined at a single C atom
are called spiro compounds.
 These are often chiral even when
they seem symmetrical.

AXES, CENTRE AND PLANE OF

SYMMETRY
 Centre of symmetry or inversion
centre, abbreviated i. A molecule
has a centre of symmetry when, for
any atom in the molecule, an
identical atom exists diametrically
 opposite this centre an equal
distance from it.

 Plane of symmetry: a plane of

reflection through which an identical
copy of the original molecule is
generated. This is also called
a mirror plane and abbreviated σ.
 Rotation-reflection axis/
Alternating axis of rotation: An
axis around which a rotation by
(360/n)˚, followed by a reflection in a
plane perpendicular to it, leaves the
molecule unchanged. Also called
an n-fold improper rotation axis, it
is abbreviated Sn.

 Symmetry axis/ Axis of

symmetry : an axis around which
a rotation by (360/n)˚, results in a
molecule indistinguishable from the
original. This is also called an n-
fold rotational axis and
abbreviated Cn.
 

RESOLUTION OF RACEMIC
ENANTIOMERS
 Separation of two enantiomers is
called Resolution.
 It can be achieved by converting the
racemic enantiomers into
diastereomers.
 The steps involved in the process
are:
 Conversion of enantiomer mixture to
diastereomers (acid-base reaction)
using enantiomerically pure sample
of acid or base.
 Chiral acids, such as (+)-tartaric
acid, (-)-malic acid, (-)-mandelic acid,
and (+)-
camphor-10-sulfonic acid, used for
resolution of racemic mixture of bases.
Chiral bases, such as brucine,
strychnine, and quinine are used for
resolution
resolution of racemic mixture of
acids.
Simpler amines of synthetic origin
such as 2-amino-1-butanol,
amphetamine,
and 1-phenylethanamine are used on
resolution of enantiomeric mixture.

 Diastereomers can be separated by

physical means such as
chromatography, evaporation,
crystallization.
RESOLUTION VIA
CHROMATOGRAPHY

Interactions even weaker than ionic

bonds can be used to separate
enantiomers. Chromatographic
separation relies on a difference in
affinity between a stationary phase
(often silica) and a mobile phase (the
solvent travelling through the stationary
phase, known as the eluent) mediated
by, for example, hydrogen bonds or van
der Waals interactions. If the stationary
phase is made chiral by bonding it with
an enantiomerically pure compound
(often a derivative of an amino acid),
chromatography can be used to
separate enantiomers. Chromatography
on a chiral stationary phase is especially
important when the compounds being
resolved have no functional groups
suitable for making the derivatives
(usually esters or salts) needed for the
more classical resolution.
In essence, enantiomers behave
identically except when they are
placed in a chiral environment.
A good way of visualizing this is to
imagine turning a steering wheel in the
direction of the numbering. If you are
turning your car to the right, you have
R; if you are turning to the left you have
S.
Note that the units of a measured optical rotation α are
degrees, but, by convention, specific rotation [α] is
quoted without units.
z
Tartaric acid