Stereo Chemistry

Stereo Chemistry

Molecules that are attached to four different groups a, b, d and e are chiral.

A tetrahedral carbon that is attached to four different group is known as a chiral centre, a chiral carbon atom, an
asymmetric centre or an asymmetric carbon atom. Now a days a more modern term stereo genic centre is used.

It we have to find, the presence of a stereo genic centre in a given molecule then we have to check if it is chiral. For
example C-2 is stereo genic centre in 2-butanol.

A stereogenic centre has four different groups. (a) In 2-chloropentane, C-2 satisfies this requirement. (b) None of the
carbons in 3-bromopentane have four different substituents, and so none of its atoms are stereogenic centres.

In the following examples, the stereo genic carbon is indicated by an asterisk. But remember carbons that are part of
a double bond or a triple bond cannot be stereo genic centres.

In a ring, carbon atom can be stereogenic center if it is attached to two different substituents and the path traced
around the ring from that carbon in one direction is different from that traced on the other side. For example the
carbon atom which is attached to methyl group in 1,2-epoxypropane, is a stereogenic centre. The sequence of
groups in CH2–O as one proceeds clockwise around the ring from that carbon, but it is O–CH2 in the anticlockwise
direction. In limonene C–4 is stereogenic centre.
Prob. Identify the stereogenic centers, if any, in
(a) 2-Cyclopenten-1-ol
(b) 3-Cyclopenten-1-ol

Answer (a) The hydroxyl-bearing carbon in 2-cyclopentene –1– ol is a stereogenic center.

(b) There is no stereogenic center in 3-Cylcopenten-1-ol, because the sequence of atoms 1®2®3®4®5 is equivalent
regardless of whether one going through clockwise or anticlockwise.

Molecules which have more than one stereogenic centre may or may not be chiral.
An optical isomer can exist in four forms :

(i) Dextrorotatory (d or +form) It rotates the plane polarised light towards clockwise directions

(ii) Laevorotatory (l or – form) It rotates the plane of polarised light towards anti clockwise.

(iii) Racemic mixture (dl or ± form) It is equimolar mixture of d and l form. It is optically inactive due to external
compensation. i.e., the rotation caused by ‘d form’ is neutralised by ‘l form’

(iv) Mesoform : Optical isomer with a plane of symmetry is called meso form. It is optically inactive due to internal
compensation, i.e., the rotation caused upper half of the molecule is neutralised by lower half.
Meso tartaric acid

In any molecule cause of optical isomerism can be discussed in two ways :

(i) Optical isomerism due to chirality

(ii) Optical isomerism without chirality

(i) Due to chirality : A compound is optically active if it is chiral or asymmetric, i.e., it should be non–superimposable
upon its mirror image. The chirality can be achieved either due to presence of chirality carbon atom or absence of
elements of symmetry.

Certain structural properties related to molecular symmetry can sometimes help us determine by inspection whether
a molecule is chiral or achiral. For example, a molecule that has a plane of symmetry or a centre of symmetry is
superimposible on its mirror image so it is achiral.

A plane of symmetry bisects a molecule so that one half of the molecule is the mirror image of the other half. The
achiral molecule chlorodifluoromethane, for example, has the plane of symmetry.

A point in a molecule is a centre of symmetry if any line drawn from it to some element of the structure will, when
extended an equal distance in the opposite direction, encounter an identical element. For example cyclobutane
derivative lacks a plane of symmetry, yet is achiral because it possesses a centre of symmetry.

Elements of symmetry : There are two elements of symmetry

(a) Plane of symmetry :

It may be defined as a plane which divides a molecule in two equal parts that are related to each other as an object
and mirror image.

(b) Centre of symmetry : It may be defined as a point in the molecule through which if a line is drawn in one direction
and extended to equal distance in opposite direction, it meets another similar group or atom.

Chiral molecules with two stereogenic centres

When a molecule contains two stereogenic centres, as does 2,3-dihydroxybutanoic acid, or tartaric acid type
molecule how many stereoisomers are possible ?

The answer can be determined to be 4 by applying a common sense approach but remember if molecule like tartaric
acid is there than mesoform becomes inactive due to molecular symmetry.

Stereoisomer I is not a mirror image of III or IC, and so it is not an enantiomer of either one. Stereoisomers that are
not related as an object and its mirror image are called diastereomers; diastereomers are stereoisomers that are not
enantiomers. Thus stereoisomer of III and a diastereomer of IV. Similarly, II is a diastereomer of III and IV.

In order to convert a molecule with two stereogenic centers to its enantiomer, the configuration at both centres must
be changed. Reversing the configuration at only one stereogenic centre converts it to a diastereomeric structure.

When the carbon chain is vertical and like groups are on the same side of the Fischer projection, the molecule is
known as the erythrodiastereomer. When like groups are on opposite sides of the Fischer projection, the molecule is
termed as the threo diastereomer. Thus, as seen in the Fischer projections of the stereoisomeric 2,3-
dihydroxybutanoic acids, compounds I and II are erythro stereoisomers and III and IV are threo.
FIGURE Stereoisomeric 2,3–dihydroxy butanoic acids. Stereoisomers I and II are enantiomers. Stereoisomers III and
IV are enantiomers. All other relationships are diastereomeric.

Because diastereomers are not mirror images of each other, they can have, and often do have, markedly different
physical and chemical properties. For example, the (2R,3S) stereoisomer of 3-amino-2-butanol is a liquid. While the
(2S,3R) diastereomer is a crystalline solid.

(1) Wedge representation

Three types of lines are used to represent the spatial arrangement of a system.

(a) Thick lines – Shows such bonds which comes towards viewer.

(b) Dotted lines – Shows such bonds which move away from the viewer.

(c) Normal lines – shows such bonds which are present in the plane of the paper

(2) Sawhorse Representation

(3) Newman projection representation

Two central carbon atoms which are shown by point and circle.

(4) Fischer projection representation

Four bonds of a carbon atom are shown by the sign of +. In this presentation vertical line always shows such bonds
which are away from the observer while horizontal line shows those bonds which are projected towards the observer.
For example
this is not correct representation because vertical line are always away from the observer

this is correct representation because vertical lines have away groups

Optical isomerism in alicylic compounds

Prob. How many stereoisomers of (a) methylcyclopropane and (b) methylcyclobutane are possible? Draw them.

Ans. See figure below. One stereoisomer of each; there is a plane of symmetry (dashed line) through the CH3 and H
bisecting the ring. Monosubstituted carbocyclic compounds do not have stereoisomers.

Prob. Draw all the stereoisomers of (a) 1,2-dimethylcyclopropane, (b) 1,2-dimethylcyclobutane, and (c) 1,3-
dimethylcyclobutane.

Ans. For (a) and (b) see figure below. Three each: cis-1,2 are meso, and trans-1,2 exist as a pair of enantiomers in
each case.
(c) See figure below. Two: cis-1,3 has a plane of symmetry; trans-1,3 has a plane and a center of symmetry. In both
isomers C1 and C3 are stereocenters. Switching H and Me converts one stereoisomer to another.

Prob. Draw all the stereoisomers of 1,2- and 1,3-dimethylcyclopentanes.

Ans. See figure below. Cyclopentane is best considered as a flat ring. All trans-isomers exist as a pair of
enantiomers. All cis-isomers are meso.

Specific terms related with stereochemistry

Diastereomers show different physical properties, e.g., melting and boiling points, refractive indices, solubilities in
different solvents, crystalline structures, and specific rotations. Due to their differences in solubility they often can be
separated from each other by fractional crystallization; because of slight differences in molecular shape and polarity,
they often can be separated from each other by chromatography. Diastereomers show different chemical properties
toward both chiral and achiral reagents. Neither any two diastereomers nor their transition states are mirror images of
each other and so will not necessarily have the same energies. The DH‡’s (energy of activation) will be some what
different and thus the rates of reaction will also differ. However, since the diastereomers have the same functional
groups, their chemical properties are not too dissimilar.

The chemical properties of enantiomers are the same towards achiral reagents, solvents, catalysts, and conditions.
But towards chiral reagents, solvents, catalysts, and conditions, enantiomers react at different rates. The transition
states produced from the chiral reactant and the individual enantiomers are not mirror images of each other. They are
diastereomeric, and they hence have different enthalpies; the DH‡ values are different, as are the rates of reaction
and the amounts of product formed. With the exception of rotation of plane-polarized light, enantiomers have identical
physical properties. e.g., boiling and melting points, and solubility. (b) The chemical properties are the same towards
achiral reagents, but chiral reagents react at different rates. Enantiomers are optically active; the racemate is optically
inactive--it does not rotate the plane of polarized light. Other physical properties, such as crystalline form, melting
point, and solubility, of an enantiomer and its racemate may differ.

(a) Stereoselective reaction

Reaction in which a single starting material has the capacity to form two or more stereoisomeric product but forms
one of them in greater amounts than any of its stereoisomers. Terms such as addition to the less hindered side
describe stereoselectivity. This term is more closely connected with structural effect in the reactant as expressed in
terms such as addition to the less hindered side.

Addition of halogen on alkene is stereo selective

(b) Stereospecific reaction

Reaction in which stereoisomeric starting materials gives stereoisomeric products. Stereospecific is more closely
connected with features of the reaction itself than with the reactant. Thus terms such as syn addition and anti
elimination describe the stereospecifity of reactions.

A stereospecific reaction can also be stereoselective, for example, syn addition shows stereospecificity in the
catalytic hydrogenation of alkenes while the preference for addition to the less hindered face of the double bond
describes stereoselectivity.

E2 Elimination is always stereospecific, for trans elimination leaving group –H and –X must be as far apart as
possible. Elimination is always anti in nature for example

Prob. The most suitable conformation for E2 reaction is ;

(c) Optical inversion

Reversal of the three–dimensional arrangement of the four bonds to sp3 hybridized carbon. It occurs in Nucleophilic
substitution of SN2 type also known as walden inversion.

Prob. What is the nature of the products in the following :

 There is no change in configuration.

Q. What do you think about the following compounds — they are having chirality or not.

hence it is chiral compound.

(d) There are no chiral carbon, but the molecule is chiral (an
allene)
(e) Planar molecule – achiral.
Q. For each of the following pairs of structures, identify the relation between them. Are they enantiomers,
diastereomers, structural isomers, or two molecules of the same compound?
Ans. (a) There are four stereoisomers. A and B are enantiomers, as are C and D. (b) A and B are diastereomers of C
and D.

Ans. (a) We might expect that four stereoisomers are possible (2n = 4). An allowed 180° rotation of A in the plane of
the paper gives B; A and B are superimposible and thus identical, and so there are only three stereoisomers. The
stereoisomer A or B is called the meso form, and it is achiral and optically inactive. (b) See figure below.

Prob. (a) Why is a meso compound achiral? (b) What structural properties must a meso compound have?

Ans. (a) At least one conformer has either a plane or a point of symmetry, which makes it superimposible upon its
mirror image. (See, for example, A and B in Problem) (b) It must have at least one pair of similar stereocenters.

Prob. Draw meso-2,3-butanediol (a) in the Fischer representation showing a plane of symmetry and (b) in the
sawhorse representation showing (i) a plane in the eclipsed conformer, and (ii) a point in a staggered conformer.
Q. Why are the following stereoisomers meso?

Ans. In (a) and (b), a plane of symmetry cuts through the centre carbon and the two horizontal ligands revealing that
the top half of the molecule is the mirror image of the bottom half. It does not matter which ligands are attached to this
carbon because they are within the symmetry plane. This is also true in (c) if n = 1 or an odd number. However, if n is
an even number, the symmetry plane cuts through the central C¾C bond.

In the case of allenes, there is a central carbon with sp bonding, 1,2-diene system forces the ligands attached to the
terminal of the allene system to occupy mutually perpendicular planes and thus creates molecular asymmetry. The
same conditions apply to spirans.

Biphenyls are twisted from the achiral conformation as a result of steric strain between the ortho substituents on
adjacent phenyl group. Actually both rings are perpendicular to each other so generation of molecular asymmetry
occurs in the molecule which forms mirror images.

Gauche conformation of butane is chiral and structures above are non-superimposable mirror-images of each other,
known as conformational enantiomers.

(vii) Cyclo octatetraene is not planar and aromatic due to angle strain it forms tub shape structure. It is not chiral but
its tetramethyl derivative is chiral since it has no plane of symmetry.

(ix) Bromination of E and Z 2-butene

Anti addition of Br2 to Z–2–butene

gives a racemic mixture of (2R, 3R)
and (2S,3S), 2,3-dibromobutane
through chiral bromonium ion in
which olefin geometry is maintained.
Either of the two equal approaches of Br-- on the bromonium ion carbons are enantiomeric. The original olefin
geometry changes, thus it gives (±) 2,3-dibromobutane.
Anti addition form chiral bromonium ion in which geometry of alkene is maintained. Either of the anti attack by Br--
changes the original geometry and thus trans alkenes give meso (optically in active) product.

Normally in an SN2 reaction the incoming nucleophile undergo back attack so inversion of configuration with respect
to stereo chemistry of substrate. In case the incoming nucleophile and the outgoing leaving groups are same for
example when 2-Iodo-octane with sodium iodide, the reaction becomes reversible and an equilibrium is setup
between the two enantiomers, leading to recemization, if we do the reaction between optically active 2-iodo-octane
and radioactive iodide ions. This is one of the simplest possible types of bimolecular substitution reaction and
involves replacement of iodide ion by radioactive iodide ions so that product and starting material are chemically
identical.

The cumulated bonding system (compounds with two or more successive double bonds) with an even number of
double bonds do not have a plane of symmetry or a centre of symmetry show optical isomerism and must be
resolved into enantiomers but cumulative diene with odd number of carbonation shows geometrical isomerism
because if allene chain of

compound is extended by one more double

bonds, one then gets a system in which the substituted groups at the two ends of the cumulated chain now lie in the
same plane and shows geometrical isomerism.
Prob. 2,3-Pentadiene, CH3CH == C == CHCl has no chiral C’s, yet it is a chiral molecule (it has two enantiomers).
Explain

Resolution of racemic mixture

In most of the reactions optically active compounds are obtained in the form of a racemic mixture The method of
separation of (+) and (-)forms is known as resolution. The physical and chemical properties of enatiomers are same
so they cannot be separated by common methods like distillation as crystallisation. So there are same specific
techniques to separate them which are described below:

(a) Mechanical separation:

This is the oldest method used to separate racemic mixture. Pasteur (1948) was the first person to use this
technique. This technique is based on the fact that crystals of enantiomers are not same, but they are mirror images
of each other. These crystals can be separated under powerful microscopes with the help of forceps.

(b) Biochemical method :

This technique was first of all used by Pasteur. This technique is based on the fact that some micro-organisms like
yeast, fungi, bacteria etc destroy one form, from the racemic mixture. The other form is left behind , so it can be
separated very easily.

For example :- If mould penicilliam qlaucam is grown on racemic mixture of ammoniam tartrate, pencilliam destroys
d-ammoniam tartrate but l - ammoniam tartrate is left behind in the mixture. This can be separated by crystallisation.
(1)The selection of appropriate strain of bacteria is very difficult.

(2)Bacteria cultivate in very dilute solutions so it takes more time to separate the substance by crystallisation.

(3) Bacteria destroy one form from the mixture so we get only one form by this method hence it is costly.

This method is used for the separation among first of all the of acids. Racemic mixture of amino acids is acetylsed
then it is left with yeast. Yeast produce an special enzyme known as amylase. It acts as a catalyst in the process

(c) Chemical method

This is the best method used for the separation of racemic mixture. This was used by Pasteur in 1858. This method is
generally used for the separation of optically active acids and bases. If the racemic mixture is acidic it is reacted with
optically active base and if it is basic it is reacted with optically active acids to form salts As the solubilities of these
salts differ from each other so they can be separated by crystallisation. This method is also known as salt formation
method.
Example:

These salts are hydrolysed and the acid is liberated. This method is also used for alcohol, aldehydes, ketones etc.

(d) Column chromatographic method

This is the modern technique which is now used very frequently. Henderson and Rule (1939) used this method for the
separation of camphor derivatives. This method is based on the principle of chromatography. According to it, the rate
at which a molecule flows through the column adsorbent material is dependent on the shape and size of the
molecule.
We pour the racemic mixture on a column filled with the adsorbent material. One form is readily adsorbed at the top
of the column but the other goes down, later both these forms can be separated very easily.

Conformational Isomers

The isomers which differ in the conformation are known conformational isomers. This type of isomerism is found in
alkanes and cycloalkanes and their substituted derivatives

(a) Conformation of alkanes

According to Kemp and Pfitzer there is restricted (but not free) rotation about a single bond. The restricted rotation
leads to the existence of a single compound of one configuration into more than one spatial arrangements
(conformations). So now conformation may be defined as the term used to denote any one of the infinite number of
spatial arrangements of the atoms of a molecule that can arise from rotation about a single bond.

(b) Difference between conformation and configuration

The term conformation should not be confused with the configuration which relates to those spatial
arrangements of the atoms of a molecule that can be changed only by the breaking and making of bonds
whereas the spatial arrangements in conformation are changed simply by rotation about a single bond. In
other words we can say that the various stereoisomers that differ in configuration can be inter converted only by the
breaking and making of bonds whereas the conformational arrangement may be inter converted by rotation of one
part of the molecule with respect to the rest of the molecule about a single bond joining these two parts. The various
conformations of some of the important compounds are dealt below to clarify the point.

(c) Representation of conformation

Conformation of alkanes can best be represented with the help of Newmann projection formulae since eclipsing
(overlapping or crowding) of hydrogen atoms can best be represented by this formula. In the Newmann projection
formula, the carbon atoms nearer to the eye (i.e., the front carbon) and the groups attached to it are represented by
equally spaced radii and the distant carbon atom (i.e., the carbon atom farther from the eye or the rear carbon) and
the groups attached to it are represented by a circle with three equally spaced radial extensions.
(d) Conformations of Ethane

The conformation of ethane, H3C—CH3 affords the simplest possible introduction of the subject. Imagine that one of
the methyl groups is rotated along the C—C axis keeping the rest of molecule undisturbed methyl group are possible,
each of these possible arrangement represent a conformation.

However, for the sake of convenience each rotation is done in the instalment of 60°. Thus in such case we will obtain
six different conformations of ethane. Of these six conformations, the two extreme ones are worth studying because
these are very much different from each other, while the intermediate four conformations are almost similar to each
other but of course different from the two extreme forms. Thus in short there will be three conformations of ethane,
the two extremes and the third one will be the intermediate of the two extremes.

1. One extreme conformation will be such in which the rear methyl group is completely eclipsed by the front methyl
group and thus only the front methyl group, i.e., three hydrogen atoms of the methyl group nearer to the eye are
visible. Such conformation is known as eclipsed conformation. In the Newmann projection formula of the eclipsed
form, the hydrogen atoms are crowded, i.e., the two hydrogen atoms come close to each other.

2. Another extreme conformation will be such in which the rear methyl group has been rotated upside down and thus
both the methyl groups, i.e., all the six hydrogen atoms are visible and are as far apart from each other as possible.
Such conformation is known as staggered (most stable).

3. The infinite number of possible intermediate conformations between the two extreme conformations are referred
to as skew conformations. In these conformations, hydrogen atoms are closer than in staggered but away than in
eclipsed conformation.

It important to note that all the above conformations of ethane are not equally stable.

Staggered > Skew > Eclipsed

The energy difference between the staggered and eclipsed conformations of ethane is found to be 2.8 kcal/mole
which constitutes the energy barrier to rotation about the C—C bond, i.e., for the conversion of staggered to eclipsed
conformation.
 However, this energy barrier of 2.8 kcal/mole is too small for either form to remain stable, i.e., the two forms are inter
convertible because even at ordinary temperature, ethane molecules have an average energy 15–20 kcal/mole which
can easily overcome the small barrier of 2.8 kcal/mole.
This implies that rotation about the carbon–carbon single bond in ethane is almost free for all practical purposes, and
it is not possible to separate the different conformations of ethane. Remember that ordinarily, ethane is mostly in
staggered form.

Cyclohexane has two conformations, e.g., boat and chair form. Chair form is more stable than the boat form by 44 kJ
mole-1.

It should be noted that even though different conformations of a compound cannot be separated, the study of
conformations known as conformational analysis proves quite useful to the chemists. This is because stabilities and
shapes of different conformations are of considerable help in understanding the properties of compounds.