Stereo Chemistry

Chapter

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 asymmetri c centre
or an asymmetric carbon atom. Now a days a more modern term stereogenic centre is used.
It we have to find, the presence of a stereogenic centre in a given molecule then we have to check if it is chiral. For example C-2 is
stereogenic 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 stereogenic carbon is indicated by an asterisk. But remember carbons that are part of a double bond
or a triple bond cannot be stereogenic centres.


In a ring, carbon atom can be stereogenic center if it is attached to two different substituents and the path traced around t he 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 CH2O as one proceeds clockwise around
the ring from that carbon, but it is OCH2 in the anticlockwise direction. In limnolesne C4 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 12345 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; these will be discussed later.
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 nonsuperimposible 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 th e
erythro diastereomer. 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 2,3dihydroxy butanoic acids. Stereoisomers I and II are enantiomers. Stereoisomers III and IV are
enantiomers. All other relationships are diastereomeric.























Stereo Chemistry

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.



Mainly four types of presentation are used to express three dimensional structure of molecules in stereo chemistry.
(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
In this representation a tilted line shows the central C C bond.


(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

Note here that staggered conformation cannot be directly converted into fischer projection formula because it has always vert ical
line with away bond group so first change staggered form in appropriate manner followed by inter conversion.






R/S nomenclature
Cahn, Ingold and Prelog gave following rules for R/S nomenclature R & S are Latin presentation and here R stands for rectus
means clockwise or right side rotation for light while S stands for sinister means anti clockwise or left side rotation for light.
These rules are also known as sequence rules.
(1) When different atomic number having atoms of four substituents are directly attached with a C atom then priority of groups is
considered according to their atomic number for example

Four substituents H, CH3 OH, Br
Priority order Br > OH > H > OH

(2) Isotopes are considered on their mass number bases for example


(3) When same atoms are directly attached with a carbon atom, then priority order is given by next atom attach to these atoms so


(4) Multiple bonds in the molecules are considered in following way










Following examples easily express the sequence rule














Stereo Chemistry

(5) First draw the fisher projection formula of the system, if the group follows clockwise path according to sequence rule, then
system is named as R and in case of anticlockwise path, the system has S name but remember 4
th
group must be present on
vertical line.
(6) If 4
th
group is placed on horizontal line then opposite names are given to the system.



Many other examples are given below where many carbon atoms are present and so we give R/S nomenclature to them.







D/L nomenclature

This is another nomenclature to represent the two different form of optically active compound. Following rules are taken to give
D/L nomenclature
(1) Draw the fisher projection formula, taking most oxidised group at the top of the vertical line.
(2) H and OH group must be placed on the horizontal line.
(3) If OH group is present on right hand side of the fisher projection formula, then D isomer while if OH group is present in
left side than if is L isomer.
(4) When a compound containing more than one chiral carbon atom, then highest number of chiral centre in a compound is
considered for D/L nomenclature.







Always remember that you can make two exchanges of groups in a fischer projection formula and any fischer projection can be
rotated by 180 in a plane of paper



Determine the number of optically active isomers in the following examples
(1) 2-bromo-3-chlorobutane optically active isomer




(2) 2,3,4 tribromopentane 2n 1 = 22 1 = 2 (due to molecular symmetry)


















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 DHs (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 threedimensional 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.

Prob. 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.
Prob. 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 (2
n
= 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.



Prob. 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 CC bond.
Compounds are optically active mainly due to molecular asymmetry which give rotation to
light. Many other examples are also possible which show optical activity (enantiomers) due
to molecular asymmetry.
(i) Silicon and germanium containing compounds exist as enantiomers.


(ii) Quaternary ammonium salts exist as isolable enantiomers


(iii) Chirality of sulphone and sulphoxide due to different isotopes




(I) Ethyl methyl amine is a chiral amine but it cannot be resolved due to rapid conversion of
lone pair of N atom inside out at room temperature (flipping). The best way to picture
amine inversion is to compare it to an umbrella in a wind storm. Amine (II) in which the
chirality is due to the presence of stereogenic carbon atom can however, be resolved into
enantiomers. Very interesting point here that phosphorous containing compound phosphines
and sulphur containing compound sulphoxide, sulphonium salt for example


Have the same geometry as 3 chiral amine but these compounds are resolvable because they
undergo inversion comparatively very slowly than amines.
(v) Several molecules which do not have a stereo center are however optically active due to
molecular asymmetry, they form non-superimposible mirror images.


A pair of enantiomers of 2,6-dimethylspiro [3,3]-heptane
These molecules contain chiral axis, where as 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.
(vi) Several molecules for example hexahelicene gives chirality due to helical shape even
though they do not contain stereo centre. However fusion of benzene ring in a linear fashion
as in nepthalene, anthracene etc. does not generate chirality. However, if rings are added to
produce a curve, the addition of the sixth ring produces a chiral molecule.



(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.
(viii) In case of compounds which contain both a stereocentre and a double bond, for example
3-penten-2-ol exists in four forms (two enantiomers and two E Z forms).



(ix) Bromination of E and Z 2-butene






















Anti addition of Br
2
to Z2butene gives a racemic mixture of (2R, 3R) and (25,35), 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.




Racemization of a chiral biphenyl occurs if the size of ortho substituents is small and they
slip past each other (rotation is possible). The coplanar conformation thus attained has a plane
of symmetry and is achiral.
Prob. Define the terms erythro and threo and illustrate with Fischer diagrams using 3-chloro-
2-butanol (CH
3
CH(OH)CHClCH
3
).
Ans. These terms are used to describe diastereomers with two chiral Cs (usually adjacent),
when both Cs have two sets of identical ligands. In figure below the identical ligands are H
and Me. When the different ligands, in this case OH and Cl, are on the same side of the
vertical bonds as in figure below (a), the molecule is called erythro (related to the



sugar crythrose). When they are on opposite sides as in figure above (b), the molecule is
called threo (related to the sugar threose). The relationship of the erythro to a meso structure
is apparent if we change OH to Cl.
Prob. 2,3-Pentadiene, CH
3
CH == C == CHCl has no chiral Cs, yet it is a chiral molecule (it
has two enantiomers). Explain


Prob. Draw the two enantiomers of 4-chloroethenylcyclohexane, C, shown in figure below
(a).
Ans. This is best done by considering the ring to be flat. (b).



Prob. Spiro compounds are bicyclic compounds having one C common to both rings as
shown below. Draw the enantiomers of (a) 2-chlorospiro[4,5]decane and (b) 8-
chlorospiro[4,5]decane.



Ans. See figure below. The two rings are in different planes, making the situation reminiscent
of the allenes.




Prob. Write the structures of the three meso diastereomers of C
6
H
12
C
l2
.
Ans. Here meso structures can be identified easily by their plane of symmetry in at least one
of their conformations, which divides them into mirror image halves, each with three Cs.
The isomers are:




Prob. (a) What is the necessary condition for a pair of conformational enantiomers to be
isolable? (b) Draw the enantiomers of the following compound and explain the structural
feature which makes their isolation possible.




Ans. (a) The rotational energy barrier must be high enough so that interconversion of
enantiomeric conformers does not occur. (b) See figure below. This molecule has a high
enthalpy of activation for rotating about the bond due to the bulky substituents on the two
benzene rings which prevent the rings from slipping past each other. (Note: These
substituents prevent the two rings from being flat in the same plane.)




Prob. Point out all the chiral centers in 1-methyldecalin. How many stereoisomers exist?




Ans. The three chiral Cs in figure below are encircled, and there are four racemic pairs of
enantiomers or eight stereoisomers.
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 chromatagraphy. 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, H
3
CCH
3
affords the simplest possible introduction of the
subject. Imagine that one of the methyl groups is rotated along the CC 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. Among
the infinite number of conformations the staggered conformation in which hydrogen atoms
are as far apart as possible is the most stable while the eclipsed conformation in which
hydrogen atoms are perfectly eclipsed is the least stable; stabilities of the skew conformations
lie in between these two extreme limits. Hence the relative stabilities of the various
conformations of ethane are in the following order.

Staggered > Skew > Eclipsed

This stability order can be explained in terms of repulsive interactions (nonbonded) between
bonding pairs of electrons, i.e., electrons pair which form six CH bonds in ethane. In the
staggered conformation, the electron clouds of six carbonhydrogen bonds are as far apart as
possible with the result there is minimum repulsive interactions between these electron
clouds. Hence this conformation is quite stable. On the other hand, in the skew and eclipsed
conformations, the electron clouds start coming closer. This causes repulsive interactions
which is maximum in the eclipsed conformation where there is minimum separation of the
electrons of the six CH bonds. Hence the potential energies of the skew and eclipsed
conformations increase and thus their stabilities decrease which is minimum in case of
eclipsed conformation.

The repulsive interaction between the electron clouds which affects the stability of a
conformation is known as torsional strain. Of all the conformations of ethane, staggered
conformation has the least torsional strain and hence most stable while eclipsed conformation
has the maximum torsional strain and hence least stable. Due to torsional strain, certain
energy called torsional energy, is required to allow rotation around the CC single bond. In
other words, an ethane molecule having staggered conformation will have to cross an energy
barrier equivalent to the torsional energy for being converted into eclipsed conformation.

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 CC 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
1520 kcal/mole which can easily overcome the small barrier of 2.8 kcal/mole. This implies
that rotation about the carboncarbon 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.


(e) Conformations of Propane
Propane can be regarded as derived from ethane by replacing its one of the hydrogen atoms
by a methyl group. Since it has two CC bonds, rotation about CC single bonds.
However, like that of ethane, rotation about CC single bond is almost free and difference in
energy between staggered and eclipsed forms is 3.3 kcal/mole. Again since energy difference
is too small to permit a separation of the two extreme conformations of propane, propane
molecule exists mostly in the most stable staggered conformation; eclipsed conformation
again is the less stable.



(f) Conformation of nButane
nButane may again be considered as a derivative of ethane whose one hydrogen on each
carbon is replaced by a methyl group.



Thus it has three CC single bonds around which rotation can take place, with the result, n
butane is somewhat a complex molecule as far as study of conformation is concerned.
However, if we consider rotation around the central CC bond (C
2

C
3

), the situation becomes almost similar to that of ethane conformation with the difference that
here more than one staggered and eclipsed conformations are observed.

(g) Staggered conformations
From our previous discussion we know that staggered conformations have lower torsional
energies and hence are more stable than eclipsed conformations. In case of nbutane
three staggered
conformations are possible.



In anti or trans conformation, figure I the methyl groups are as far apart as possible, i.e., they
are 180 apart and hence this conformation is the most stable. On the other hand, in gauche
conformations, II and III, the two methyl groups are only 60 a part, i.e., they are crowded.
Due to crowding of the methyl groups, the van der Waals forces of repulsion being to operate
and raise the energy of the conformations which thus become less stable. In other words, the
gauche forms are unstable than the anti form due to steric repulsion between methyl groups in
the former (i.e., steric strain is developed in the molecule). Both anti and gauche forms are
free of torsional strain.

Here it is important to note that the two gauche staggered conformations II and III are non
superimposable mirror images of each other, therefore, they are known as conformational
enantiomers. Similarly, like other stereoisomers the pair comprising of the anti form I and the
gauche form II or III are termed as conformational diastereomers.

From the energy study of these three conformations, it is found that the anti conformation, I is
slightly more stable than the gauche conformations II or III only by 0.9 kcal/mole. Such
staggered conformations which either do not differ or differ
slightly in energy from each other are termed as conformational isomers or conformers. Thus
here I, II and III conformations of butane are conformers. It is important to note that the
conformational isomers are readily inter convertible and hence cannot be separated
(difference from the conventional stereoisomers).


(h) Eclipsed conformations of nbutane
Like that of three staggered conformations, there are three eclipsed conformations of n
butane.
In the fully eclipsed form IV, a methyl group is eclipsed by another methyl group, while in
eclipsed forms, V and VI, each of the methyl group is eclipsed by hydrogen. Of these two
types of eclipsed conformations, the one having larger methyl groups eclipsing, i.e., IV, will
naturally feel more repulsive force than the V and VI where a methyl group is eclipsed with a
hydrogen atom. Thus out of these three conformations, IV is less stable while V and VI are
more stable.



Following important conclusions can be drawn from the above discussion.

(i) The fully staggered form (anti form) I is more stable than the fully eclipsed form IV by
about 5.3 kcal/mole (22 kJ/mole).

(ii) The anti form I is more stable than the gauche forms II or III by about 0.9 kcal/mole (3.8
kJ/mole).

Thus the relative stabilities of the six conformations of nbutane can be represented as below.



Lastly, note that the energy difference of 5.3 kcal/mole between the anti form I and the fully
eclipsed form IV is still too small to permit their separation. In other words, rotation about the
CC single bond in nbutane is almost free.

Thus at any time, nbutane consists of an equilibrium mixture of all possible conformations,
of course with the highest proportion of the anti form, I and the least proportion of the fully
eclipsed form IV.

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.