Stereochemistry

Contents:-

►Introduction

►Defination

► Classification

►Optical ismerism

►Geometrical isomerism

►Conformational isomerism

►Stereochemistry of allenes,spiran,biphenyls

► Resolution of racemic mixture

►Racemic switches

►Important Terminology

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 Stereochemistry

Stereochemistry:

The study of the three-dimensional structure of molecules

Structural (constitutional) isomers:

Same molecular formula but different bonding sequence

Stereoisomers:

Same molecular formula, same bonding sequence, different spatialorientation

Basic Concepts of Stereochemistry

Isomers are molecules that have the same molecular formula but different
arrangements of their constituent atoms. Constitutional isomers (structural isomers)
have different bonding arrangements of their atoms (connectivity) and usually show
very marked differences in physical and chemical properties. Connectivity differences
can involve the carbon skeleton or the nature and position of functional groups

Stereoisomers are molecules with identical connectivity but different spatial

arrangements of their constituent atoms that cannot be interconverted by bond
rotation.

Stereochemistry, a subdiscipline of chemistry, involves the study of the relative

spatial arrangement of atoms within molecules. An important branch of
stereochemistry is the study of chiral molecules.[1]

Stereochemistry is a hugely important facet of chemistry and the study of

stereochemical problems spans the entire range of organic, inorganic, biological,
physical and supramolecular chemistries

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Classification:-

(A) Structural isomers (Constitutional isomers) :

- Having different sequence of bonding of their atoms as with molecular formula

C2H6O , which may represent ethanol (CH3CH2OH) or dimethyl ether (CH3OCH3) as
Functional isomers,

C4H10 may be either butane or isobutane as Chain isomers, and

C3H7Cl may be 1-chloropropane or 2-chloropropane as Position isomers.

- Glucose and fructose are structural isomers.

- Tautomers which are structural isomers of different energies which are

interconvertible via low energy barrier,the isomerization involve atom or group
migration.

Keto-enol isomerization involve change in position of proton

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 Stereochemistry

(B) Stereoisomers :

- When the isomers have same sequence of covalent bonds but differ in
the relative disposition of their atoms in space, the difference is
stereoisomers.

eg. Enantiomers, Diastereomers (Epimers,Anomers ), Rotamers(Conformational

isomers)

Another type of stereoisomerism is called mirror-image stereoisomerism.

Mirror-image related stereoisomers are said to be left-handed and right handed
and occur when a molecule and its mirror image are non-superimposable.

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Concept of Chirality:

The term ‘chiral ’ is taken from the greek word cheir meaning handedness.

An object that is not superimposable on its mirror image is called ‘ Chiral ‘

and is unsymmetrical while the object that is superimposable on its mirror
image is called ‘Achiral ‘ and is symmetrical.

- The radical bromination of butane to form 2-bromobutane appears to

yield single product.

- The 2-bromobutane molecules formed by the radical bromination of butane are

actually nonsuperimposable and are therefore not identical.

- A molecule that is not superimposable on its mirror image is said to be

‘chiral’

- In this case each isomer is called an ‘enantiomer’.

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 Stereochemistry

A chiral molecule is a type of molecule that lacks an internal plane of symmetry

and has a non-superimposable mirror image. The feature that is most often the
cause of chirality in molecules is the presence of an asymmetric carbon atom.

The term chiral (pronounced /ˈkaɪrəl/) in general is used to describe an object that
is non-superposable on its mirror image.

Achiral (not chiral) objects are objects that are identical to their mirror image.
Human hands are perhaps the most universally recognized example of chirality:
The left hand is a non-superposable mirror image of the right hand; no matter how
the two hands are oriented, it is impossible for all the major features of both hands
to coincide. This difference in symmetry becomes obvious if someone attempts to
shake the right hand of a person using his left hand, or if a left-handed glove is
placed on a right hand.

The term chirality is derived from the Greek word for hand, χειρ (cheir). It is a
mathematical approach to the concept of "handedness".

In chemistry, chirality usually refers to molecules. Two mirror images of a chiral

molecule are called enantiomers or optical isomers. Pairs of enantiomers are often
designated as "right-" and "left-handed."

Molecular chirality is of interest because of its application to stereochemistry in

inorganic chemistry, organic chemistry, physical chemistry, biochemistry, and
supramolecular chemistry.

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 Stereochemistry

-
A chiral molecules -- (1) two representatives

3- methylhexane

3-methylpentane

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 Stereochemistry

3-methylpentane is achiral.

3-methylhexane is chiral

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 Stereochemistry

- racemic mixture - a 50:50 mixture of two enantiomers

a clockwise direction, then the other enatiomer will rotate
d - dextrorotatory - (+) enantiomer Þ rotate clockwise.
for example the (d,l) or (+,-)-3-methylhexane mixture:
If one enantiomer rotates plane polarized light by x° in
plane polarized light by x° in the counterclockwise direction.

Chirality in organic molecules:

-A molecule to be chiral if it is not superimposable on its mirror image.

-A molecule in which carbon is attached to four different groups or atoms is
said to be chiral in nature and is known as Stereogenic centre (or chiral centre
or Assymetric centre)
-A molecule with one stereogenic centre is always chiral. Also chiral molecules
do not have plane of symmetry.
Often, asymmetric atoms are marked with an asterisk.
Molecules having one stereocenter are always chiral.

Enantiomers – Optical isomerism:

The stereoisomers of a compound which are

nonsuperimposable mirror images of each other are termed as ‘ Enantiomers
’.
A molecule with one stereogenic centre always exists in enantiomeric forms.
-Enantiomers cannot be distinguished on the basis of their physical properties,
such as boiling points, melting points, and densities.

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-Enantiomers can be distinguished by the way they interact with plane

polarized light.
When plane polarized light is passed through a sample of one of the enantiomers,
the plane of polarization is rotated either clockwise or counterclockwise. When
the experiment is repeated with the other enantiomer, the plane polarized light is
rotated an equal amount, but in the opposite direction.
If facing the light source:
• Clockwise rotation: enantiomer is dextrorotary (+)
• Counterclockwise rotation: enantiomer is levorotary (-)
This interaction with light is called optical activity and enantiomers are often
called optical

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 Stereochemistry

Each enantiomer of a pair has the same physical and chemical properties in
achiral environment with exceptions of their interaction with

(1) Plane polarized light (optical activity)

(2) chiral reagents
The enantiomers of tartaric acid have same melting point (171 o) and same value
of pKa
(25oC pK1=2.98 ;pK2 =4.34) ,but different signs of specific rotation (+)-tartaric
acid has (+12.7) while
(-)-tartaric acid has (-12.7).
Each enantiomer shows same chemical reactivity with achiral reagents.

Optical rotation is measured with a polarimeter.

Light is electromagnetic radiation that oscillates perpendicular to its direction of

motion.

The oscillation of light can be resolved into two perpendicular components.

When light is passed through a polarizer, only one of the two perpendicular
components of light is passed through. This light is referred to as plane-polarized
light.

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 Stereochemistry

When plane polarized light interacts with a chiral molecule, the plane of
polarization of the light is rotated to the left or right.
This effect is called optical rotation and the molecule is said to be optically active.
Optical activity is measured using a polarimeter. This device contains a light
source, a polarizer to produce the plane polarized light, a sample cell, and an
analyzer to determine the amount of rotation.
The measured rotation (in degrees) is the observed optical rotation, a, of the
sample.
The value of a depends upon:
• Structure of the chiral molecule
• Concentration of the chiral molecule
• Length of the sample cell
• Wavelength of the light
• Solvent used
• Temperature.
The specific rotation, [a], of a sample is defined for each chiral molecule (the
value is solvent dependent):

Apolarizer measures the degree of optical rotation of a

compound


  Τ
λ =
lxc

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 Stereochemistry

[  ] T = specific rotation
a is the measured rotation in degrees

l is the path length in decimeters

c is the concentration in grams per mL

T is the temp in °C

l is the wavelength

Optical rotation indicates enantiomeric composition.

A racemic mixture is a mixture of equal amounts of the + and – enantiomers of a
chiral compound. It shows no net rotation of plane polarized light.
When one enantiomer equilibrates with its mirror image, the process is called
racemization.
When one of the two enantiomers of a chiral compound is present in a mixture in
excess over the other there will be a net rotation of plane polarized light.
A 50% enantiomer excess would be defined as a mixture of 75% one enantiomer
and 25% of the other (50%+ with 25%+ and 25%-). The mixture would be called
50% optically pure.
The optical purity of an enantiomer is defined:

    observed 
% optical purity   100   enantiomer excess
   
 

Any non-racemic chiral substance is called scalemic.[8]

A chiral substance is enantiopure or homochiral when only one of two possible

enantiomers is present.

A chiral substance is enantioenriched or heterochiral when an excess of one

enantiomer is present but not to the exclusion of the other.

Enantiomeric excess or ee is a measure for how much of one enantiomer is

present compared to the other. For example, in a sample with 40% ee in R, the

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 Stereochemistry

remaining 60% is racemic with 30% of R and 30% of S, so that the total amount of
R is 70%
Diastereomers:

Diastereomers (diastereoisomers) are stereoisomers that are not enantiomers.

Diastereomerism occurs when two or more stereoisomers of a compound have
different configurations at one or more (but not all) of the equivalent (related)
stereocentersand are not mirror images of each other. When two
diastereoisomers differ from each other at only one stereocenter they are
epimers. Each stereocenter gives rise to two different configurations and thus to
two different stereoisomers.
Diastereomers have different physical properties like
m.p.,b.p.,solubility,retention times,and Rf value and having different rates of
reactions even in achiral environment.

CHO CHO CHO

H OH H OH HO H

HO H HO H HO H

HO H H OH H OH

H OH H OH H OH

CH2OH CH2OH CH2OH

D-Mannose
D-Galactose D-Glucose

( Diastereomers )

Here, D-Galactose and D-Glucose are C-4 epimers while D-Glucose and D-
Mannose are C-2 epimers.

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 Stereochemistry

Diastereoselectivity is the preference for the formation of one or more than one
diastereomer over the other in an organic reaction.Cis-trans isomerism and
conformational isomerism are also forms of diastereomerism.
Two stereocenters can give four stereoisomers: chlorination of 2-bromobutane
at C3.
Consider the chlorination of 2-bromobutane. Several products are formed but
consider only the 2-bromo-3-chlorobutane.
A second stereocenter is formed by the addition of the chlorine atom.

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 Stereochemistry

The Diastereomers which differ in the configuration at C-1 are called Anomers.

H H
H OH
HO O HO O
HO HO
HO H HO H

H OH H H

H OH H OH

-D-Glucose β-D-Glucose
Meso compounds:
Two identically substituted stereocenters give rise to only three stereoisomers.
Consider the radical bromination of 2-bromobutane:

Since there are 2 chiral centers in the product, we might expect 4 distinct
stereoisomers: RR, RS, SR, and SS.
These could then be organized into enantiomeric pairs: RR | SS and RS | SR.

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A closer look at the RS and SR pair of molecules, however shows that they are
superimposable molecules and are therefore identical.
A compound containing 2 or more stereocenters that is superimposable with its
mirror image is called a meso compound.
Meso compounds contain an internal mirror plane which divides the two halves
of the molecule which are mirror images of each other.

Meso compounds
The achiral molecules even though they contain stereogenic centers, they have a
plane of symmetry.

threo

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 Stereochemistry

erythro≡
meso
Geometrical isomerism:
The compounds having similar molecular formula but different arrangement of atoms
or groups in space around the double bond are called geometrical isomers and
phenomenon is known as geometrical isomerism which is due to restricted rotation
about C-C double bond which causes the breaking of л bond.
Condition for geometrical isomerism:
An alkene of the type abC=Cxy exhibits geomtrical isomerism if a≠b and c≠d.
In alkene if either of the double bond carbons is attached to two identical groups or
atoms, no geometrical isomerism will exist.

CH3 CH2Cl CH3 C6H5

C=C C=C
CH3 H CH3 C6H5

(Do not exhibit geometrical isomerism)

The configuration of the geometrical isomerism is designated by
( 1) E-Z system and (2) cis-trans system
Double bonds: E/Z Configuration:
For alkenes and similar double bonded molecules, the same prioritizing process is
followed for the substituents. In this case, it is the placing of the two highest
priority substituents with respect to the double bond which matters. If both high

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priority substituents are on the same side of the double bond, ie. in the cis
configuration, then the stereoisomer is assigned a Z or Zusammen configuration.
If, by contrast they are in a trans configuration, then the stereoisomer is assigned
an E or Entgegen configuration.

In organic chemistry, cis-trans isomerism or geometric isomerism or configuration

isomerism or E-Z isomerism is a form of stereoisomerism describing the
orientation of functional groups within a molecule. In general, such isomers
contain double bonds, which cannot rotate, but they can also arise from ring
structures, wherein the rotation of bonds is greatly restricted. Cis and trans isomers
occur both in organic molecules and in inorganic coordination complexes.

The terms cis and trans are from Latin, in which cis means "on the same side" and
trans means "on the other side" or "across". The term "geometric isomerism" is
considered an obsolete synonym of "cis-trans isomerism" by IUPAC

It is sometimes used as a synonym for general stereoisomerism (e.g., optical

isomerism being called geometric isomerism); the correct term for non-optical
stereoisomerism is diastereomerism.

F CH3 Cl
F
C=C C=C
CH3 Cl
CH3 CH3

(E)-2-chloro-3-fluorobut-2-ene(Z)-2-chloro-3-fluorobut-2-ene

Cis-trans system:

This system used for designating the alkenes in which two olefinic carbons
have at least one similar group or atom persent on them.
The alkenes of the type abC=Cab and abC=cax exhibit cis-trans isomerism.
Trans isomers are more stable than cis isomers. In cis isomers,the groups
present on the same side experience vander waals repulsive forces due to steric
factors.

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Dipole moment used effectively for distinguishing cis and trans isomers.The
trans isomers have zero dipole moment as the bond dipole on opposite sides
cancel each other.

When the substituent groups are oriented in the same direction, the diastereomer is
referred to as cis, whereas, when the substituents are oriented in opposing
directions, the diastereomer is referred to as trans. An example of a small
hydrocarbon displaying cis-trans isomerism is 2-butene.

Alicyclic compounds can also display cis-trans isomerism.

Conformational isomerism:
Different three dimensional arrangements of atoms that result due to free
rotation about C-C bond are known as conformations. The individual structures

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 Stereochemistry

arising due to free rotation about C-C single bond are known as conformers or
conformations.
Conformations of Butane:
- Butane, CH3CH2CH2CH3 can be written as

H3C CH3

H H

H H
- If we view the molecule of butane through C2-C3 bond, each carbon is seen
attached to one methyl group and two hydrogens. A rotation about C2-C3 bond
results in the formation of number of conformations.
-The anti-form is the most stable conformation.
-The decreasing order of stability of different conformations of butane is:
Anti(Totally staggered) > Gauche(skew staggered) > skew eclipsed > Totally
eclipsed.

CH3 CH3
H CH3
H H HC H
60orotation 60orotation3 60orotation
H
H H H H H H
CH3 H3C H
(1) (2) (3)

Anti Skew eclipsed skew staggered

(gauche)

H3C CH3 CH3 H CH3

H CH3
60orotation o
60 21
Page rotation 60orotation
H CH3
H H H H H H
H H H
 Stereochemistry

(4) (5) (6)

Totally eclipsed skew staggered skew eclipsed

Fischer projection formulas II

Fischer projection
Relative configuration I
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 Stereochemistry

When no bonds to the stereogenic carbon are broken

a the reaction proceed with retention of configuration
[ reaction with retention of R,S- nomenclature ]

Relative configuration II
When bonds to the stereogenic carbon are broken
a the reaction proceed with change of configuration
[ reaction with change of R,S- nomenclature ]

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 Stereochemistry

Molecules with more than one

stereogenic center
the total number of stereoisomers = 2n
where n is equal to the number of
tetrahedral stereogenic centers

erythrothreo
Absolute Configuration: R-S Sequence Rules :-

X-ray diffraction can establish the absolute configuration.

The absolute configuration of an enantiomer is the actual spatial arrangement of
the substituent groups around the chiral centers.
There is no straightforward correlation between the absolute configuration of an
enantiomer and the sign of rotation of the molecule.

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 Stereochemistry

The absolute configuration of an enantiomer can be determined through single

crystal X-ray diffraction analysis or through chemical correlation to a molecule
whose absolute configuration has already been determined.

Stereocenters are labeled R or S.

The convention for naming enantiomers unambiguously was developed by R.S.

Cahn, C. Ingold, and V. Prelog.

The four substituents around the chiral carbon must be

first ranked in order of decreasing priority.
a highest priority
b second highest priority
c third highest priority
c lowest priority
When the molecule is positioned with the lowest priority substituent away from
the viewer, the remaining three substituents will be arranged in either a clockwise
or counterclockwise direction.
Sequence rules assign priorities to substituents:-

Rule 1:
Look first at the atoms directly attached to the stereocenter.
Precedence is in order of highest atomic number. Hydrogen is always the lowest
precedence.
A higher mass isotope takes precedence over a lower mass isotope.

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 Stereochemistry

Rule 2:If two atoms are of the same precedence using rule 1, proceed along the
two respective substituent chains until you reach a point of difference.

Rule 3:Double and triple bonds are treated as if they are single and the atoms in
them are duplicated or triplicated at each end by the respective atoms at the
other end of the multiple bond.

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 Stereochemistry

Optical isomerism of Allenes,Spirans,Biphenyl compounds (Axial chirality):

- Axial chirality: Compounds with non superimposable mirror image and it is not
possible to identify a stereocenter,in such cases chiral compounds are speak of
Axial chirality, planar chirality, and helicity.
Stereochemistry of Allenes:

Allenes are compounds which have general structure

1 & 2.
a d a a
C=C=C C=C=C
b e Page
b 27 b
 Stereochemistry

In this cumulated bonding system with even number of double bonds do not have
plane of symmetry.

In structure 1,the gp “a” and “b” lie in plane of paper,and the gp “d” and “e” in
the plane perpendicular to the plane of the paper. This molecule does not possess
a plane or center of symmetry. Which is also true for 2. Thus 1 & 2 will be
resolvable and give rise to enantiomerism.

- Compounds with odd number of cumulated double bonds display E-Z

(geometrical) isomerism.

Cumulated dienes (allenes) also exhibit chirality without having asymmetric

carbon atoms. A cumulated diene is a molecule that contains two double bonds
on a single carbon. The central carbon atoms of allene are sp-hybridized. The two
ends of allene are perpendicular because the two contiguous Πbonds use
perpendicular p orbitals on the central carbon:

Orbital view of allene, whose two ends are perpendicular.

The twisted shape of allene makes substituted allenes chiral. Consider the
following allene with methyl substituents. The mirror images are not
superimposable:

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 Stereochemistry

Enantiomers of chiral allenes

Stereochemistry of Biphenyl compounds:

- Both benzene ring of biphenyl lie in the same plane. The chirality in biphenyl
with two bulky ortho substituents in each ring (A≠B) is due to restricted rotation.
The two enantiomers can exist provided the rings display two perpendicular
disymmetric planes.
- In solution the two rings of biphenyl are twisted (45o) due to steric repulsion of
O-hydrogens.This repulsion enhances with larger O-substituents which also
arrests the rotation.

NO2
________
NO2
HOOC COOH

NO2 O2N
COOH HOOC
Chiral

(optically active)

Bulky O-substituents restrict free rotation, the rings remain orthogonal

(perpendicular to each other) .when the O-substituents on either side of inter-ring
bond are different the biphenyl becomes chiral.

The minimal condition for chirality in biphenyls:

- None of the rings should be symmetrically substituted,so that molecule can not
have plane of symmetry.Thus biphenyl is chiral (A≠B in either pair,COOH≠NO 2)
- If biphenyl is achiral,then ring 2 is symmetrically substituted (A=B=COOH)
-In order to display optical activity the substituents in the ortho position must be
large enough to prevent the two rings from becoming coplanar.

- The hydrogen atom is quite small,optically active compounds exist with two
or even three ortho positions of biphenyl occupied by hydrogen.

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 Stereochemistry

- The benzene ring that is unsubstituted in the ortho positions must have
substituents ina meta-position which have no influence on rotation but it
creates the necessary chirality of the molecule.

-Racemization of a chiral biphenyl occurs if the size of O-substituents is small and

they slip past each other (rotation is possible). The coplanar conformation thus
attained has a plane of symmetry and is chiral.

(point of symmetry)

(Diphenic acid)
HOOC

H
. H

COOH

The conformations of many biphenyl systems are restricted with regards to

rotation about the central σbond. The two conformational enantiomers of the
biphenyl molecule can be isolated individually.

A chiral biphenyl system

Stereochemistry of Spiran:

If both double bonds in allene are replaced by ring systems, the resulting
molecules are known as spirans.

- The method of naming the spiran obtains the root name from number of carbon
atoms in the nucleus, then prefixed by the term “spiro” and followed by numbers

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placed in square brackets which indicate the number of carbon atom joined to the
juction carbon atom.

Cl
1-Chloro-spiro-[5,3]-nonane

Resolution : Separation of enantiomers :-

Pure enantiomers can be obtained by first synthesizing a racemic mixure and

then separating the enantiomers formed by a process called resolution.
Resolution is best carried out by converting a racemate into a mixture of
diastereomers by adding an enantiomerically pure reagent. The resulting
diastereomers can then be separated by standard techniques.
Each pure diastereomer can then be separated into one of the original
enantiomeric molecules and the optically active reagent, which can be used again
to resolve further racemic mixtures.

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Methods of Resolution :

(1) Conversion into Diastereomers:

If the racemic mixture to be resolved contains a carboxyl group,it is possible to

form salt with optically active base.The salts are diastereomers and having
different properties like differential solubility.

When molecule does not contain a carboxyl group ,it is converted to carboxylic
acids and which may be coupled to an optically active reagent.

Racemic bases can be converted to diastereomeric salts with active acids.

Alcohol converted into diastereomeric esters and Aldehyde converted into
diastereomeric hydrazones.

(2) Differential absoption :

When racemic mixture is placed on a chromatographic column,if the colume

consist of chiral substances,the enantiomers should move along the column at
different rates and to be separable without converted into diastereomers.

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 Stereochemistry

eg. Racemioc mandelic acid completely resolved by column chromatography on

starch.

(3) Chiral recognition :

The use of chiral hosts to form diastereomeric inclusion compounds,it is possible

for host to form inclusion compound with one enantiomer of racemic host,but
not the other.This is called chiral recognition.

One enantiomer fits into chiral host cavity ,the other does not.

eg. Use of chiral crown ether to resolve the racemic amine salt.

(4) Biochemical processes:

The chiral compound that reacts at different rates with the two enantiomers
may be present in a living organism. Eg. A certain bacterium may digest one
enantiomer but not the other, here one of the enantiomer is destroyed in the
process.

(5) Mechanical separation :

This is the method by which Pacteur that racemic acid was actually a mixture of
(+) and (-)-tartaric acids.

In case of racemic sodium ammonium tartrate the enantiomers crystallize

separately – all the (+) molecules going into one crystal and all the (-) into
another.since crystals too are nonsuperimposable,their appearance are not
identical and trained crystallographer can separate them with tweezers.

This is seldom a practical method, since few compounds crystallize in this manner.
Even sodium ammonium tartrate does so only when it is crystallized below 27 o .

(6) Kinetic resolution :

Since enantiomers reacts with chiral compounds at different rates, it is

sometimes possible to effect a partial separation by stopping the reaction before
completion.

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eg. Resolution of racemic alkenes by treatment with optically active di-

isopinocam-phenylborane.

(7) Deracemization:

Here one enantiomer is converted into the other,so that a racemic mixture is
converted into a pure enantiomer. But here enantiomers must complex
differently with optically active substance.

eg. The racemic thioester was placed in contact with optically active amide,
after 28 days solution contained 89% of one enantiomer and 11% of the other.

Racemic switches:

-A racemic switch is the redevelopment in single-enantiomer form of a drug

that was first approved as a racemate.
-sometimes pharmaceutical is in only one enantiomer and other is inactive or
other enantiomer has different kind of activity .
A racemic switch refers to the conversion of a racemic mixture into its isolated
enantiomers.

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- Esomeprazole is the S-enantiomer of omeprazole. It is one of the most

successful racemic switches launched.

Generally the (±)-ibuprofene racemate is used (Brufen, Ibalgin),

but only (S)-enantiomer has the anti-inflammatory action.

Chiral drugs II
Stereoselective synthesis of (S)-Naproxene
[ Nalgesin S ]

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Some important terminology:

Stereospecific reaction:
Reaction in which particular stereoisomer of the initial
reactants results in the formation of specific
stereoisomeric products.
The stereochemistry of the initial reactant governs the stereochemistry of the
products.

Stereoselective reaction:
Any reaction in which only one set of stereoisomers is formed exclusively or
predominantly.
Also the mixture of two or more steroisomers is exclusively or predominantly
formed at the expence of other stereoisomers.

All stereospecific reaction are necessarily stereoselective but not true for vice-
versa.

H Br
H Br H

+ Br2 +
H H Br
Cyclohexene Br H
(stereospecific trans [Trans-(1R,2R)-] [Trans-(1S,2S)-]
-addition) -dibromo-cyclohexane

Enantioselective:
If reaction gives one enantiomer in preference to other, is said to be
enantioselective. Here degree of selectivity in terms of one enantiomer that is
produced relative to its mirror image.
Enantiospecific:
When only one enantiomer is formed, the reaction is said to be ..

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Chemoselectivity:
In bifunctional compound,if a reagent reacts with one functional group
preferentially,even through the other is apperently susceptible to the reaction
condition, the reaction is called chemoselective.
Eg. Reduction of a carbonyl group in the presence of cyano,nitro,or alkoxycarbonyl
group and acylation of the aromatic amino group in the presence of phenolic
group.
Regioselectivity:
Regioselectivity in a reaction, which proceed without skeletal rearrangement, is
seen when a molecule has two or more sites of reactivity arising from the presence
of one functional group,each of which reagent may attack leading the formation of
constitutional isomers. Prefentional formation of one of these isomers that
selection has occurred.
Eg.addition reaction of ,β-unsaturated carbonyl compounds and aromatic
electrophilic substitution reactions leading to meta or ortho/para products
Important concepts:

1. Isomers - Same molecular formula – different compounds.

• Constitutional – Individual atoms are connected differently
• Stereoisomers – Same connectivity – different 3D arrangement.
• Mirror-Image Stereoisomers – Related as image – mirror image.
2. Chiral Molecule - Not superimposable on its mirror image.
3. Stereocenter – Carbon atom bearing 4 different substituents.
4. Enantiomers – Two stereoisomers, each a non-superimposable mirror
images of the other.
5. Racemate – A one to one mixture of enantiomers.
6. Mirror Plane – Chiral molecules cannot contain a mirror plane.
7. Diastereomers – Stereoisomers not related to each other as mirror images
(ie. cis/trans).
8. Two Stereocenters In A Molecule – Createup to 4 stereoisomers: 2
diastereomerically related pairs of enantiomers. If the 2 stereocenters
generate a mirror plane in the molecule, the molecule is known as a meso
compound and is achiral.

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9. Physical Properties of Stereoisomers – Most are the same except for the
rotation of plane polarized light. One enantiometer rotates the plane of
polarization to the right, the other to the left. This rotation is expressed as
the specific rotation, [a].

10. Absolute Configuration - Determined by x-ray diffraction. Assignment of

R or S, as determined by the Cahn, Ingold, and Prelog sequence rules.
11.Fischer Projections - Standard 2D representation of 3D molecules containing
stereocenters.
12. Radical Halogenation - Can introduce chirality into an achiral compound.
Racemic mixtures are often produced.
13. Radical Halogenation of A Chiral Molecule Containing 1 Stereocenter -
• Gives a racemate if the reaction occurs at the stereocenter
• Gives 2 diastereomers in unequal amounts if the reaction occurs
elsewhere..
14. Stereoselectivity - Preference for the formation of one stereoisomer
when several are possible.
15. Resolution – Separation of enantiomers.
• Reaction with a pure enantiomer of a second chiral compound and
separation of the diastereomers.
• Chiral chromatography.

PREFIXES USED TO DENOTE CHIRAL

PROPERTIES:-
PREFIX PROPERTY
d-/l- Rightward (dextro), clockwise/Leftward
(leuvlo), counterclockwise, optical rotation.
Used interchangably with (+)/(-)
D-/L- Rightward/leftward arrangement of
substituents about chiral center (archaic,
used for amino acids & carbohydrates)
R-/S- Rightward (rectus)/leftward (sinister
arrangement of substituents about chiral center
(modern, used for drugs)
e.g., R-(-)- levorotatory, but with absolutes
configuration R

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References:

(1) Kalsi P.S.;Textbook of stereochemistry – conformation and

mechanism;published by New age International (p) Ltd.;5th edition; 1-12,14-
25,33-56,66-83,125-139.
(2) March Jerry; Advanced Organic Chemistry; 4th Edn; John Wiley and sons
publication; 2008; 17; 94-105,111-125.
(3) Mehta B., Mehta M.; Text book of Organic Chemistry; A. K. Ghosh
Publication; Prentice-Hall of India pvt. Ltd.; 2006;63-105
(4)Bruice P.Y.;Textbook of organic chemistry;4th edition;187-225
(5)www.wikipedia.org/enantiomer

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