28

Stereochemistry

CHAPTER

3
Stereochemistry
St ereochemistry :
It involves the study of the relative spatial arrangement of atoms within the molecules.
Dynamic stereochemistry: Dynamic stereochemistry is the study of the effect of stereochemistry on the rate
of a chemical reaction.

First Stereochemist Louis Pasteur (1849):

Significance of stereochemistry: One of the most infamous demonstration of the significance of stereochemistry was the Thalidomide disaster. Thalidomide is a drug was first prepared in 1957 in Germany,
prescribed for treating morning Sickness in pregnant women. It was discovered that one optical isomer i.e. RIsomer of the drug was safe whereas the S-isomer had teratogenic effect, causing serious genetic damage to
early embryonic growth and development.
O

O
N

1
N

H
O 4

H
N

O
H

S-isomer
O
Teratogenic effect

R-isomer

Drug for morning sickness in pregnant women.

[Remark: In human body, Thalidomide undergoes racemization: even if only one of the two stereoisomers is
ingested, the other one is produced.]
Now we have another example - Propanolol.
H

O
H
OH

R-Propanolol (contraceptive)

OH
H

S-Propanolol (antihypertensive)

29

Stereochemistry

SOME TERMINOLOGY
Optical activity: The term optical activity derived from the interaction of chiral materials with polarized light.
Scalemic: Any non-racemic chiral substance is called Scalemic.
A chiral substance is enantio pure or homochiral when only one of two possible enantiomer is present.
A chiral substance is enantio enriched or heterochiral when an excess of one enantiomer is present but not
the exclusion of the other.
Three terms are used to designate a carbon atom bonded tetrahedrally to four different substituents in a chiral
molecule.
(a) Asymmetric atom (LeBell & Vant Hoff for an atom attached with 4 different groups).
(b) Chiral centre
(c) Stereocentre.

Asymmetric atom:
Compounds with one such atom are truly asymmetric as they lack symmetry. For example
CH3

Asymmetric atom

C
C2H5

No element of symmetry
is present in the molecule.
Cl

However, there are molecules which also have atoms with four different substituents and which also have
various symmetry element including plane of symmetry as in mesotartaric acid.
Asymmetric centre
COOH
*
OH

Plane of symmetry

*
COOH

Asymmetric centre

OH

Two asymmetric center but also plane of symmetry.

Chirality is a geometric property which influences and affects all parts of a chiral molecule.

Stereogenic centre or Stereocentre:

A stereogenic centre or in short a stereocentre is an atom having groups of such nature that an interchange of
any two groups will produce a stereocentre.
1
2 OH
OHC
CH2OH
3
H4
S-form

2
CHO

CHO
OH
CH2OH

1
HO

H4
3 CH2OH
R-form

A carbon atom that is a stereocentre is also called a stereogenic carbon.

Conformation: Structures that can be interconverted simply by rotation about single bonds are conformation of the same molecule.
For example:
HH

H
H
H

H
H
Staggered conformation

HH
HH
Eclipsed conformation

Note: These two are the conformation of ethane arises due to rational possibilites across C
C single
bond.
Configuration: Structures that can be interconverted only by breaking one or more bonds have different
configuration and they are stereoisomers specifically known as configurational isomers.

30

Stereochemistry

Isomers

Constitutional Isomers
Chain Isomerism
Position Isomerism

Stereoisomers

Metamerism

Configurational Isomers

Conformational Isomer

Tautomerism
Valence Isomerism
Amine Inversion
(Invertomer)

Rotation about
single bond.

Cl

Cl
H
Conformational Isomer (conformers)

C2H5
CH3
N

CH3
C2H5

Invertomer (or Umbrella inversion)

Configurational Isomers

Configurational
Diastereomers

Configurational
Enantiomers
CH3

CH3
H

C
CH2CH3

HO

H3CH2C

H3C
H

These two are enantiomers

H
H

C
C
H
CH3
These two are diastereomers

120

CH3

H3C

H
CH3

CH3

(S)
(A)
So, (A) and (S) are mirror image of each other as shown below
H

H
H

CH3
CH3

H
H3C

H
CH3

So, these two are conformational enantiomers

Conformational Isomers

OH
H3C

CH3
C

Conformational
enantiomers

Conformational
diastereomers

31

Stereochemistry
CH3

Now, H

H
CH3

H
CH3

CH3

II

Since, I and II are not mirror image to each other so these two are conformational diasteromers.

Conformational diastereomers
Structures that are not superimpossible on their mirror image, and can therefore exist as two enantiomers are
called chiral.

Essential criteria for a molecule to be chiral. There is no any single criterion.

1.

There must be lack of element of symmetry.

Note: It is not necessary and sufficient condition because there are some set of molecules which have some
element of symmetry still they are optically active. For example.
H

Cl2

Cl1

C2
H

H
H

H
Cl2

Cl1

Optically active but having C2-symmetry.

2.

The carbon in the molecule should be attacked to four different groups.

It is not a necessary and sufficient condition also because we have an example in which carbon have four
different groups but it is still optically inactive.
For example:
COOH
H

OH

OH

COOH

Two asymmetric centre but still optically in active owing to plane of symmetry.
On the other hand we have also an example in which there is not any chiral centre but still molecule is optically
active.
For example: Properly substituted allene.
Br

Br
C

C
H

32

Stereochemistry

Not any chiral centre but still it is optically active.

Remrak: This compound is optically active not due to chiral centre but due to chiral axis.
3.

There should be an absence of plane of symmetry.

SYMMETRY ELEMENT
A symmetry element is a geometrical entity such as a line, a plane, or a point with respect to which one or more
symmetry operations may be carried out.
Symmetry Operation: A symmetry operation is the movement of a molecule about the symmetry element in
such a manner that the resulting configuration of the molecule is indistinguishable from the original molecule. The
molecule may assume an equivalent configuration or an identical configuration.
Group Theory: Mathematical study of symmetry is called group theory.
Symmetry element
Symbol
Symmetry operation
Axis of symmetry
Cn
do Cn
Alternating axis of symmetry

Sn

do Sn

Plane of symmetry

do

Point of symmetry or
centre of symmetry

do i

Identity

doing nothing.

Various types of elements of symmetry are explained below as:

(A) Axis of symmetry: An imaginary axis passing through the molecule, rotation on which by 0 gives an
equivalent orientation of molecule. It is denoted by n. Where, n = 1, 2, 3, 4, ................
Orientation: Orientation is three dimensional distribution of atoms and groups of molecule.
For example:

O
H1

H2

180

Initial orientation

H2

H1

180

Equivalent orientation

H1

H2

Identical orientation

360
2 i.e. C2 pronounced as C-two
180
Two things do an axis of symmetry.

So, the order of axis C n

Pass
Axis of symmetry
Interchange
For example in H2O.
O
C2
H1

H2

O
H2

H1

C2axis is passing through oxygen atom and interchanging H1/H2.

33

Stereochemistry
Axis of symmetry

Subsidiary axis
Axis other than
principal axis.

Principal axis
P-axis
Axis of highest
order

Let us consider another example of NH3.

N
H1

C31

H3

N
H2

H2

H1
H3
C32

These two are identical

configuration

N
H1

C33

H3

These two are equivalent

configuration

H2
H1

H3

H2

Let us consider an example of BF3.

In BF3 one C3-axis is passing through B-atom which is perpendicular to the molecular plane.
F3

F1

C3 1

B
F3

B
F2

F2

F2

C32

F1

F1

F1

C33

B
F3

F3

F2

Identical Configuration

BF3 molecule has also 3C2-axis.

(1) Passing through BF1 bond and interchanging F2/F3.
(2) Passing through BF2 bond and interchanging F1/F3.
(3) Passing through BF3 bond and interchanging F1/F2.
These three C2-axis can be represented as
C2
F1

B
(1) F3

F2

F2

F3

F2
C2(BF3)

F2

(2) F3

F3

C2

F1

F3

C2(BF1)

F1

(3)

C2

F1

B
F3

F1

C2(BF2)
F2

F1

F2

34

Stereochemistry

(B) Plane of symmetry: Imaginary plane passing through a molecule which can bisect the molecule into
two mirror image halves.
Bisect

There are two functions of a plane

Reflect

For example:
(i) bisecting oxygen atom and reflecting H1/H2.
O
H1

(ii) Bisecting all three atoms.

H2

H2

H1

H1

H1

H2

H2

(iii) Ammonia have three plane of symmetry.

(1) Bisecting H1N bond and reflecting H2/H3.
(2) Bisecting H2N bond and reflecting H1/H3.
(3) Bisecting H3N bond and reflecting H1/H2.

N
(1) H1

(H1N)
H3

H1

H2

H3

N
H2

H2

H2

(2) H1

H3

(H3N)

(3) H1

H3

(H2N)

H2

H3

H1
H2

H3
H1

(iv) BF3 is four plane of symmetry.

(1) Passing through F1B bond and reflecting F2/F3.
(2) Passing through F2B bond and reflecting F1/F3.
(3) Passing through F3B bond and reflecting F1/F2.
(4) Bisecting all the four atoms viz F1, F2, F3 and B.
(C) Centre of symmetry: A centre of symmetry is a point from which lines, when drawn on one side and
produced an equal distance on the other side, will meet identical point in the molecule.
For example: 2, 4-dimethylcyclobutane1, 3-dicarboxylic acid.
CH3

CH3

OC

NH

COOH

H
COOH
Centre of symmetry(i) CH3

N
H

CO

CH3

Centre of symmetry

Now, we want to discuss symmetry element of cyclopropane for the purpose of optical activity.
Cyclopropane have one C3 axis and three C2 axis and four plane of symmetry.

35

Stereochemistry

1.

C3-axis is passing through centre of triangle and perpendicular to all the three C2-axis.
C3-axis
H1

1
H3

2.

3C2-axis.

H2

H4

H5

H6

(a) Passing through C1 and interchanging C2/C3 or H1/H4, H5/H3 and H2/H6.
(b) Passing through C2 and interchanging C1/C3 or H2/H5, H1/H6, H3/H4.
(c) Passing through C3 and interchanging C1/C2 or H3/H6, H1/H5 and H2/H4.
3.

4 plane of symmetry.
(a) Bisecting H3 C3

H6 and reflecting C1/C2, H1/H2 and H4/H5.

(b) Bisecting H1

C1

H 4 and reflecting C2/C3, H2/H3, H6/H5.

(c) Bisecting H2

C2

H5 and reflecting C1/C3, H1/H3, H4/H6.

(d) Bisecting C1, C2 and C3 and reflecting H2/H5, H1/H4 and H3/H6.
Now, we want to make cyclopropane molecule chiral for this we will have to remove all plane of symmetry
from cyclopropane molecule. Because for a molecule to be chiral, plane of symmetry should not be present.
Case I: Mono substituted cyclopropane
Cl
Cl

H4

H1

H5

H2
H3

It has plane of symmetry bisecting ClCH1 and reflecting H2/H4 and H3/H5. So, this molecule is optically
inactive.
Case II: Homodisubstituted cyclopropane
Cl

Cl
Cl

Cl

Cl

Cl

Cl

Cl
H

Cl

Cl
H

Plane of symmetry
Achiral
Optically inactive

Plane of symmetry
Achiral
Optically inactive

Cl
H

Cl
No plane of symmetry
But C2-symmetry is present
Chiral molecule
Optically active.

Case III: Heterodisubtituted cyclopropane

H

Br
Cl

Br

H Cl

Cl

Br

Br

Plane of symmetry is present

Achiral
Optically inactive

Cl
H
H

No plane of symmetry
No axis of symmetry
Chiral
Optically active

Br

Cl

Cl
H

Br
H
No plane of symmetry
No axis of symmetry
Chiral
Optically active

36

Stereochemistry

Case - III: Trisubstituted cyclopropane.

Cl

Cl

Cl

Cl
H

Br
H

Br

Br

Plane of symmetry present.

Achiral
Optically inactive.
H
Br
H
Br

Plane of symmetry is present

Achiral
Optically inactive

Br

Cl

Br

Br

Br
H

Cl

Cl

H
Cl

Plane of symmetry present

No axis of symmetry
Achiral

Cl

No plane of symmetry
Chiral
Optically active

Problem: Find out which of the following molecule is optically active.

Br

1.

2.

Br

Cl

3.

Br

Cl

4.
F

Symmetry properties of cyclobutane.

H1

H2

1
H4

H5

H3

H6

H8

H7

Cyclopropane have one C4-axis and 4C2's axis, 4v's and one h.
1.

C4-axis passing through centre of square and perpendicular to C2' s axis.

C1
C4

2.

Cl

Cl

Cl

H
Br

Cl

C2

C3

4C2's axis.
(a) Passing through C1 and C3 and interchanging C2/C4, H1/H5, H3/H7, H4/H6, H2/H8.
(b) Passing through C2 and C4 and interchanging C1 and C3. H4/H8, H2/H6, H1/H7, H5/H3.
(c) Passing through C1C4 and C2C3 and interchanging H3/H6, H2/H7, H1/H8, H4/H5.
(d) Passing through C1C2 and C3C4 and interchanging. H4/H7, H3/H8, H1/H6, H2/H5.
4 v s
(a) Bisecting H1C1H5 and H3C3H7 and reflecting H2/H4, H6/H8
(b) Bisecting H2C2H6 and H4C4H8 and reflecting H1/H3, H5/H7.

Cl

37

Stereochemistry

(c) Bisecting C2C3 and C1C4 bond length and reflecting H2/H3, H6/H7, H1/H4, H5/H8.
(d) Bisecting C1C2 and C3C4 bond length and reflecting H1/H2, H5/H6, H3/H4, H8/H7.
(e) Bisecting C1, C2, C3 & C4 and reflecting H1/H5, H2/H6, H3/H7 and H4/H8.
Now, let us consider a case of substituted cyclobutane
Cl

H
Cl

H
H
H

Cl

Plane of symmetry
Achiral
Optiacally inactive.

Cl
H

Br

H
Cl

No plane of symmetry
Chiral
Optically active

Cl

H
Cl

Cl

Cl

Cl

Plane of symmetry.
Achiral
Optically inactive.

Cl

Cl

Br

No plane of symmetry
Chiral
Optically active

Cl

Cl

H
Cl

Cl
H

Br
No plane of symmetry
Optically active

Cl

Plane of symmetry
Optically inactive
Achiral molecule.

Cl

Cl

Cl
Plane of symmetry
Optically inactive

C6H5

COOH

C6H5

COOH

Plane of symmetry
Optically inactive

Br
Plane of symmetry
Optically inactive
C6H5

C6H5

COOH

COOH
No plane of symmetry
Optically active
Chiral molecule.

H
H
H

38

Stereochemistry

CH3
H3C

CH3
COOH

CH3
COOH

Plane of symmetry
Achiral molecule
Optically inactive.

H3C

COOH
No plane of symmetry
Chiral molecule
Optically active

CH3

Problem-2: Find out which molecules are/is optically active.

F

Cl

CH3

Cl

,
H3C

Cl

CH3

Br 4

Cl
Cl

Cl

Br
Cl

Br

Br Cl

Br 8

Br

Br

Specification of configuration R/S : Then is absolute configuration of chiral centre

Proposed by R.S. Chan, Sir Christopher Ingold, V. Prelog.
Sequence rule: Priority to the four atoms or groups of atoms attached to the chiral centre can be determined in accordance with sequence rule which are as follows.
Rule 1: If the four atoms attached to the chiral centre are all different, priority depends on atomic number,
with the atom of high atomic number getting higher priority.
Rule 2: In case of isotope, the atom of higher mass number has the higher priority.
For example among Br, C, D, H priority order is
Br > C > D > H.

e.g. 4H

2
Cl

3
SO3H

2
H3C

I1

4
H

1
Br

D3

Rule 3: If the relative priority of two groups cannot be decided by rule mentioned above, then look for next
atoms.
4

H3C

CH3

Cl

CH2

4
3
CH3

H3C

CH3

2
CH2Cl

Cl

39

Stereochemistry

Rule 4: Where there is a double bond or triple bond, both atoms are considered to be duplicated or triplicated.

H
O

C
H

CH2

C C

(1) Assign the priority sequence by above mentioned method.

(2) Find out position of the 4th group.
(3) Connect 123 making a circle.
Case I: If fourth group is below the plane.
L.P.
H.P.

L.P Low priority group.

H.P High priority group.

L.P.
Anticlockwise S

Clockwise R
2

H.P.

Ph

CH3

Note: In this case 4th group 'H' is below the plane

and rotation is clockwise so, it is 'R'.

C
HOH2C

H4

2 Ph

CH3

C
HOH2C

H.P.
D4

L.P.

Movement is clockwise
So, it is R.

Case 2: If fourth group is above the plane.

Then,
H.P.
H.P.

L.P

L.P.

Clockwise movement S

Anticlockwise movement R

For example:
4

2 Cl

CH3

C
1

Br

Note: In this case 4th group is above the plane,

So, clockwise movement gives 'S'.

i-Pr

Case III: If the fourth group is on the plane then do double interchange in such a way that the 4th group
undergoes below the plane.

40

Stereochemistry

For example:
H4
2
CH2CH3
CH3
3

C
1 HO

In this case 4th group is on the plane.

Double interchange can be done as

2
H

CH2

C
HO

CH2CH3
CH3

First
Interchange

C
HO

CH3
Second
Interchage

CH2

CH3

H 4

H3C

CH3

OH

1
'S'
SOLVED PROBLEMS
2

3
C

Me

HOOC

Cl

NH2

COOH

H4

HOOC

Ph

H4

OH

IV

III

SMethyl dopa

Ph

OH

Sform

Cl

4
1

COOH

Me

II

4
COOH

CH2Br

C
HO

Br

Note: In this case fourth group is on the plane. So, we will have to do double interchange as shown below
3 CH2Br
COOH

CH2Br

CH2Br

HO

First
Interchange

C
HO

Br

1
HO

Me

3
2
O

COOH

1
2
F3C

H4

S-Proline

4
COOH

2 OH
CH3

H3C

1
3

N 1

Br

Br

COOH

Second
Interchange

OH R

R
3

H3C 4

41

Stereochemistry

PROBLEMS
1.

Find R/S of the following compounds

OH
Me
H2N

CO2H

NHMe

MeO

CO2H
N
MeO

MeO

1
Me

Me2N
Ph

Ph

OH
H

H3C

HO

CH3

HO

OH

OH

OH

OH

OH

OH

10

11

12

R/S Nomenclature in Fischer projection.

Horizontal Line

Intersection of these two lines represent C-atom.

Vertical Line

Vertical Line away from the viewer.

Horizontal Line Towards the viewer.
Towards the viewer

Away from the viewer

For R/S nomenclature.

Assign priority sequence.
Case I: If fourth group is present on the top or bottom of vertical line then

H.P.

L.P.

Clockwise R

L.P.

H HO

H3C

O
Me

C2H5

Ts

H
C C

OH

OH

H.P. Anticlockwise S

42

Stereochemistry

For example:
4

1
NH2

H3C

2
H3C

3
CH

COOH

H3C

NH2

2
COOH
R

H
4

Case II: If 4th group is present on left or right side of the horizontal line then.

L.P.
H.P.
Anticlockwise R

L.P.
H.P.
Clockwise S

For example:
3

CH3
2 COOH

1
NH2

H2N
1

COOH

Ph

4
H

3 CH
H
4

3 CH3 S

4
C2H5

H3C

OH

OH

C2H5

S 1

For example:
3
Ph

OH

HO

Et

CHO

R
2

3
H3C

4
CH3
C2H5

Br

Conversion of Fisher Wedge.

OH

CH2OH

CH3

(i) Cl

H3C

Cl

OH
H

OH

HO

(ii) H

OH

Et

OH

HO

CH3

Et

CH3
HO

H3C

(iii) H

H
H

CH3
OH

OH

HO
CH3

OH

H3C

or

H
H3C

HOH2C

HOH2C

OH

or

HO
H
HO

Note: In all conversion, the configuration (R/S) should not be change.

CH3

or

OH
H
Et

43

Stereochemistry
CH3

H3C

OH

OH

H
H3C

OH
H

OH
HO

C2H5

C2H5

or
H

OH

CH3

Conversion of fischer to sawhorse.

FW
2nd carbon

CH3
H

OH

OH

Note: Consider at first carbon shape like

(Pronounced 'Y')

First
C2H5
carbon
H

OH

At first carbon

OH

At 2nd carbon
C2H5

CH3

and then combine these two by a straight line like

CH3

H
H

H
H

OH
OH

Ph

OH

OH
C2H5

CH3

Me

Me

Me

H Me

H
Ph

OTs

OTs

C2H5

Note: Since Fischer projection is represented in eclipsed form so the resulting sawhorse should also be in
eclipsed form if we have need of staggered form we can obtain it by simple rotation.
For example:
H
Me

Me

Me

60

H
Me

Ph

Ph

OTs

OTs

Staggered form is suitable for elimination reaction since, for

E2 elimination, the two departing group should be trans.

Eclipsed form

H
Me

Me

Me

OC2H5

+ C2H5OH + OTs

Ph

Me

Ph

TsO

Conversion of Fischer to Newmann:

Me

2nd carbon

HO

C2H5

HO

C2H5
Me

1st Carbon
eclipsed form

C2H5
C2H5

HO
HO

eclipsed form
Me
Me

Me
HO

C2H5

C2H5
Me

Staggered
form
OH

44

Stereochemistry
CH2OH
HO

C2H5

H
OH

HO
H

OH

OH

OH

C2H5
C2H5

C2H5

C2H5

Eclipsed form
2nd carbon
COOH
HO
H

OH
H

OH

HO

1st carbon

HO

2nd
carbon

COOH

COOH
H

HO

COOH 1st carbon

COOH

COOH

How we can apply these interconversion into reaction mechanism.

Let us consider addition of Br2 on cis-2-butene.
CH3

2.

H3C

H + Br2

CH3

Br

Br

Br

H3C

CH3
H

H
H3C

C
C

H3C

Br
C

H
Br

H
H

H3C

Br

CH3

Br

CH3

CH3

Br

Br
CH3

(A)

Br
H

Br
H3C

CH3

H3C

Br

By rotation

Br

H3C

Br

Br
H

CH3

CH3
Br
CH3

Br

Br

H
CH3 (B)

So, A and B are non superimposable mirror image to each other and hence They are enantiomers.
Enantiomers: Enantiomers are the stereoisomers which are non superimposable mirror images to each other.
So these two steroisomers have opposite descriptor.
H3C

CH3

HO

C2H5

OH

C2H5

R
Non super imposable mirror image.
Opposite descriptor i.e. one is R and other is S.

3
4

CH3
S1

CH3

H
H

Cl
R

OH

C2H5

(A)

Cl
HO

R
S
C2H5

(B)

H
H

45

Stereochemistry

So, in compound A and B, the configuration at chiral centre are

In A

In B

C2

C2

C3

C3

So, these two are enantiomer

Properties of enantiomer:
1. All physical properties such as M.P., refractive index, vapour pressure, relative density, NMR spectrum, IR spectrum are same except direction of optical rotation. (Magnitude is same but direction is
opposite).
2. All the chemical properties of enantiomers towards achiral reagent are always identical.
3. The chemical properties of enantiomers will be different in the following condition.

1
2
3
3.

Reagent Solvent
Catalyst
Chiral
Achiral Achiral
Achiral
Chiral
Achiral
Achiral
Achiral Chiral

Result
Difference in rate of reaction.
Difference in rate of reaction
Difference in rate of reaction

Note: If we run NMR spectrum of enantiomers in chiral solvent then it will be also different.
What is the relation between following compound.
Ar

CO2Me

Ar

CO2Me

So, these two compounds are enantiomer.

Diastereoisomers:
Diastereomers are the strereoisomers that are not enantiomers.

Some important points regarding the diastereoisomers.

1. Diastereomers can arise when structures have more than one stereogenic centre.
2. The magnitude of optical rotation of diastereoisomers are always different but the direction may be same
or opposite.
3. The physical properties of diastereomers are always different but difference may be more or less.
4. The chemical properties of diastereomers toward chiral as well as achiral reagent is always different.

Examples of diastereoisomers:
HO2C
HO2C

CO2H
Maleic acid
m.p. 140142C

CO2H
Fumaric acid
m.p. 299-300C

Note: geometrical isomers (i.e. cis and trans isomers) are always diastereoIsomers. A similar stereoisomers
can exist in cyclic compounds.
For example: 4-t-butyl cyclohexanol.
OH

OH

cis-isomer
because OH and t-Bu group
are projected in same direction
m.p. 82-83C

Trans-isomer
m.p. 80-81C

So, these two stereoisomers are called diastereomers.

46

Stereochemistry

Note: Diastereoisomers can be chiral or achiral.

OH

Ar

HO

CO2Me
O

(i)

Ar

CO2Me
O +

(ii)
These two diastereoisomers are chiral because
plane of symmetry is not present.

Plane of symmetry

Plane of symmetry present

So, achiral diastereoisomers.

NHMe

NHMe
These two are diastereomers.

OH
Ephedrine

OH
Pseudoephedrine

Remark: The diasteroisomers are different compounds with different names (For example ephedrine and
pseudoephedrine) and different properties, while the pair of enantiomers are the same compound and differ
only in the direction in which they rotate plane polarized light.
In summary if we have compound having two chiral centre each one R/S then
RR

Diastereoisomers

RS

Enantiomer
SS

Diastereoisomers

SR

Enantiomer

For example:

OH
HO2C

OH

R
R

HO

HO2C

CO2H

diastereoisomers

S COOH
enantiomers
OH

OH
S

HOOC S
COOH

OH

HO

enantiomers

HOOC

R COOH

HO
diastereoisomers

Meso Compounds:
Compounds that contain stereogenic centres but achiral are called meso compounds. This means that there is
a plane of symmetry with R stereochemistry on one side and S stereochemistry on the other.

47

Stereochemistry

For example:
Plane of symmetry
optically inactive

Plane of symmetry

Br
OH

OH
OH

CO2H

HOOC

OH

OH

Cl

Cl

OH

OH

OH

HO

OH

Mirror
plane

Plane of symmetry
Achiral
Meso Compound

So Meso compound
Optically inactive

Br
Meso Compound

Conversion of Newmann into Fischer and relation between two compounds.

H

Cl

Cl

Br

C2H5

OH

H3C

Br

CH3

OH

(A)

(B)

Br
OH

Cl
H

HO
Cl

CH3
C2H5

H
Br

(B)
Br
H

R CH3

Cl
OH

Br
2

CH3
C2H5

OH
4

(A) C2H5
3
So, A and B are diastereomers.
Br

Cl

Ph

H3C

NH2

Br

&

Cl

(A)

CH3
Br

Cl

Since, in (B) C2H5 group is attached with back carbon and

we want to bring it at front carbon so we will have to rotate
it by 180.

C H
CH3 2 5

(A)

C2H5

NH2

H3C
H

Ph

(B)

What is the relation between A and B.

S
R

Cl
OH

C2H5 (B)

48

Stereochemistry
Ph

BrCl

Cl

H
Br

H NH2

Br

(i)

(ii)
Ph

Ph

CH3

Cl

NH2

Ph
S
H

3
1

CH3

NH2

CH3

H
Br

Cl
S
CH3

So, these two are diastereomers

PROBLEMS
1.

What is the relation between A and B.

Cl
H

C2H5

CH3

Br H

HO Cl

Cl
Br

H3C

HO

CH3
C2H5

OH

(A)

Br
H

S
C2H5

(B)

(B)
CH3

Br H

Cl
HO

Cl
HO

H3C

Br
H

So, A and B are identical.

C2H5

C2H5

(A)
What is relation between P and Q.
NH2
HO
HOOC

CH3

HO

NC

NC
CH3

Q
NC
OH

H2N

HO
H2N

CH3

CH3
R
OH
R

NC

COOH

CN
NC

CH3
COOH

CH3
COOH

H2N

NH2

CN

NC

NC

COOH
CN

HO
H2N

CN
NC

COOH

NH2

49

Stereochemistry

So, P and Q are diastereomer.

CH3
H

2.

OH

Br

HO

CH3

C2H5

C2H5

Br

The molecules represented by the above two structures are

(a) Identical
(b) Enantiomers
(c) Diastereomers
CH3

(d) Epimer

CH3

OH

Br

OH We can write this structure

by simple rotation
H

Br

C2H5

C2H5

So, these two compounds are identical.

3.

The following two compounds are

CH3
S

H
H

OH

HO

OH
R
C2H5

HO

S H
C2H5

(a) Enantiomers
Soln. (a)
4.

CH3
R

(b) Diastereomers

(c) Identical

(d) epimer.

Which one of the following statement regarding the projections shown below is true?
H

Cl

H3C

Cl

Cl

CH3
H

CH3

CH3

Cl

(B)
(A)
(a) A and B represent the same configuration. (b) Both A and B are optically active
(c) B is optically active.
(d) A is optically active
Soln.

Cl Cl

H H

Cl

Cl

CH3
CH3
CH3

CH3
CH3

CH3
Cl

Cl

H
CH3

(A)

Cl

Cl

H
CH3

(B)

50

Stereochemistry

A is optically inactive due to presence of plane of symmetry. (Correct answer is (a))

5.

Match List-I with List-II and select the correct answer using the code given below the lists.
List-I
List-II
A. Meso compounds
1. An equimolar mixture of enantiomer
B. Enantiomers
2. Stereoisomers that are not mirror images
C. Diastereoisomers
3. Non-superimposable mirror images
D. Racemate
4. An optically inactive compound whose molecules are achiral
even though they contain chiral centre.
A
B
C
D
(a)
3
4
1
2
(b)
3
4
2
1
(c)
4
3
1
2
(d)
4
3
2
1
Soln. (d)
6.
What is the correct Fischer Projection formula for the compound represented by the following Newmann
Projection?
HO

CH2OH
H

HO

H
CHO

CHO
HO

(a) H

OH

HO

(b) HO

(c) HO

CH2OH

Soln. HO

OH

HO
H

CHO
CH2OH

CHO

OH
H

OH

(d) H

OH
CHO

CHO

HO

CH2OH

CH2OH

CHO

CH2OH
HO

CHO

CH2OH

H
OH
CH2OH

Correct answer is (a)

7.

Which one of the following Newmann projection formulae correctly represents a meso structure?
Ph

Ph

(a)

OH

OH
Ph

Soln.

(b)

HO

Ph

OH
H

Ph

Ph

(c)

Ph

OH

OH
H

(d)

HO

HO

H
Ph

51

Stereochemistry

Ph

Ph

Ph
H

OH

HO

OH

Ph

OH

HO

OH

OH

HO

Ph
H
HO

H
HO

OH
H

OH
H

Ph

OH

HO

HO

H
Ph

H
OH

H
Ph
Ph

Ph

Ph
OH

HO

HO

HO

Ph

HO
H

Ph
Ph

Ph

Ph

HO
HO

Ph
Ph

Ph
Ph

Ph

Ph

H
OH
Ph

Ph

c has plane of symmetry so, it correctly represents a meso compound.

CHO

8.

OH
CH2OH

Which is the correct order of priority of groups attached to the chiral carbon in the compound given above
while as assigning R or S configuration.
(a) HO > CHO > CH2OH > H
(b) H > CH2OH > CHO > OH
(c) CHO > OH > CH2OH > H
(d) CH2OH > CHO > OH > H
Soln. (a)
9.

Which one is the correct configurational assignment (in terms of CIP principle) for each of the compound listed
below?
2
1
H2N

1
ClH2C

COOH
4
CH3

S
3
Ph

3
COOH
C

C
4H

H3CH2C 2

II

I
(a) I-R, II-S
(b) I-S, II-E
(c) I-L, II-S
Soln. (d)
10.
Consider the following configuration of 2, 3-dibromobutane.
CH3

Br

(1)

CH3

Br

CH3

CH3

H
Br

(d) I-S, II-Z

(2)

Br
H

CH3

(3)

Br

Which one of the following is the correct answer?

H
CH3

Br

52

Stereochemistry

(a) Conformation (1) is the meso-form while (2) and (3) are an enantiomeric pair.
(b) Conformation (2) is the meso-form while (1) and (3) are an enantiomeric pair.
(c) Conformation (3) is the meso form while (1) and (2) are an enantiomeric pair.
(d) Conformation (1) and (2) are identical and (3) is the meso-form.
Soln.
Br

Br

CH3

CH3

H
Br

CH3

Br

Br

Br
H

Br
CH3

CH3

R
CH3

Br

CH3

CH3
R

Br

Br

CH3

CH3

Br

Br

CH3
S
S

H
CH3

CH3
CH3

Br

Br

Br

CH3
(2)

CH3

(3) having plane of symmetry

So, it is a meso compound.

(1)
So, these two compounds are enantiomers

11.

Br
Br

Br
H

CH3

CH3

So, the correct statement is conformation (3) is the meso while (1) and (2) are an enantiomeric pair.
Consider the following statements regarding the given projections.
CH2OH

CH2OH

Br

HO

HO

CH3

(A)

CH2OH

Br

OH

HO

CH2OH

CH3

CH3

CH3

(B)

(C)

(D)

CH2OH
H

Soln.

HO

Br

HO

CH3

H
CH3

(D)

CH2OH

Br

OH

HO

R
S
CH3

(B)
H

HO

CH3

(A)
HO

(d) 1 & 3.

CH2OH

CH2OH
HO

HO

(1) (A) and (C) are diastereoisomers.

(2) (D) is the Newmann projectoin of (B).
(3) (B) may be named as thereo-1, 2, 3-butanetriol.
Which of the above statements are correct?
(a) 1, 2 & 3
(b) 1 & 2
(c) 2 & 3

HO

(C)

OH

CH2OH

H
H

OH

HO
CH2OH
CH3

H
CH3

H
H

53

Stereochemistry

So, A and C are diastereomers.

D is not the Newmann projection of B.
HO
H

H OH

The Newmann projection of B is

CH2OH
CH3

Soln. (d).

Epimers
Epimers are the diastereomers, differ in the stereochemistry at only one stereocentre.
The term can be applied only to the chiral compound having more than two chiral center.
For example glucose and glactose have difference in configuration at C4 so they are epimers at C4.
1

CHO

CHO

R 2H

OH

OH

S 3 HO

HO

R 4 H

OH

HO

OH

5H
6

OH

CH2OH

CH2OH

Glactose

Glucose

Similarly glucose and mannose have change in configuration at C2 so they are epimers at C2.
1

CHO

CHO

R 2H

OH

HO

S 3 HO

HO

R 4 H

OH

OH

OH

OH

5H
6

H
H

CH2OH

CH2OH

Mannose

Glucose

*
OH

*
(A)

*
(B)

OH

Compound (A) and (B) are epimeric pair.

Anomers:
Anomers are the diastereomers (in the case of a monosaccharide) which differ in the configuration at C1 are
called anomers.

54

Stereochemistry

-anomer

CH2OH

CH2OH

O H

O OH

-anomer

H
H

OH
OH

OH
OH

OH

OH
H
-D-glucose

OH

-D-glucose

PROBLEMS
1.

Identify the correct set of stereochemical relationship amongst the following monosaccharides I-IV.

OH

OH
O

OH

OH

OH
O OMe

OH
OMe

OH

OH

OH

OMe

OH

OH
O OMe

OH

OH

OH

II
I
(a) I and II are anomers; III and IV are epimers.
(c) I and II are epimers; III and IV are anomers.
Soln. (d).

OH

OH

III
IV
(b) I and III are epimer; II and IV are anomers.
(d) I and III are anomers; I and II are epimers.

Threo and Erythro nomenclature

Threo and Erythro nomenclature are based on sugar chemistry.
CHO

same

CHO

OH

HO

OH

CH2OH
D() erythrose

different

H
OH

CH2OH
D() threose

Erythrose and threose are diastereomers.

A molecule with two adjacent stereocentres, when there are two groups which are common to each
carbon while third is different i.e. Cabx Caby gives rise to erythro and threo diastereomer.

Procedure for finding erythro and threo diastereomers.

Step I: Find out the group or atom which is not common on two adjacent asymmetric centre.
Step II: Placed this different group on top and bottom position of vertical line in Fischer projection formula.
Step III: And arrange the rest group or atoms around horizontal position of Fischer projection.
Case I: If two similar group are on the same side then it is called erythro.
Case II: If two similar group on the opposite side then it is called threo.

55

Stereochemistry

For example:
CH2CH3
H

Br

Br

These two are different group on the two

asymmetric carbon placed at top and bottom.

CH3
These two H, atoms are projected in same side so, it is erythro

CH2CH3
Br

Br
CH3

In this structure the two similar group viz H and Br are opposite so, it is threo.
Note: The terms erythro and threo are generally applied only to those molecules which do not have symmetric
ends.
In summary, condition for erythro and threo nomenclature:
(1) Two asymmetric carbon should be there
(2) On two asymmetric carbon, two of the groups are the same and the third is different.
2.

Consider the following statements about the Fischer projection A D.

COOH

CH3

HO

HO

Br

CH3

CH3

OH

Br

HO

Br

Br

CH3

CH3

CH3

CH3

(A)

(B)

(C)

(D)

(1) A and B are erythro forms while C and D are threo forms.
(2) There must be two assymetric carbon
(3) C is a meso form while B and D are dL form.
(4) A and B are meso-form while C and D are diastereomers which of the above statements are correct?
(a) 1, 2 and 4
(b) 2, 3 and 4
(c) 3
(d) 2 and 4
Soln. (c)

3.

Which of the following compounds can be represented as threo and erythro isomers?
OH

OH

Br
CH3

(1) Ph
Br

CH3

(2) H3C

CH3

(3) Ph

OH

(a) 1 & 2
(b) 1 & 3
(c) 1 & 4
Soln. (b) Hint Condition for erythro and threo are Cabx Caby.

OH

Br

Br

(d)
H3C

(d) 2 & 4

CH3

56
4.

Stereochemistry

Consider the following statements. In the elimination reaction.

CH3
Ph

CH

Ph

CH

Base

Ph

CH3
C

HBr

Br

C
Ph

(1) Of the various stereoisomers of the reactant, only stereoisomers of proper geometry, that is antiperiplanar
conformation will undergo this elimination reaction.
(2) Erythro isomer will undergo elimination reaction at a faster rate.
(3) The threo isomer will form the trans olefin of these statements.
(a) 1, 2 & 3 are correct
(b) 2 & 3 are correct
(c) 1 & 3 are correct
(d) 1 & 2 are correct.
Soln.

Br

Br

Ph

Ph

Ph

Ph

H
CH3

CH3
erythro isomer

Threo Isomer

H
H

Ph

Ph

Ph

Ph

H
Br

Br

CH3

CH3
H

Ph

B:
Br

H3C

Ph

Ph

Ph

Br
CH3
H

Ph
Rate of elimination will not be faster
because the two bulky Ph group projected
in the same direction causes steri chindrance
and will increase the activation energy of this
conformation.

H3C

Ph

trans product

Correct answer is (c)

5.
Find out the stereoisomers of 3-bromo-2-butanol
Soln. 3-bromo-2-butanol have two asymmetric centre. So, the total number of stereoisomers = 22 = 4
These are
CH3

CH3

CH3

OH

HO

Br

Br

Br

CH3

Erythro enantiomers

CH3

CH3
OH
H

HO

Br

CH3
Threo enantiomers

CH3

57

Stereochemistry

(A) Optically activity in biphenyls

Two conditions are necessary for biphenyl compounds to exhibit optical activity.
(i) Neither ring have a vertical plane of symmetry.
(ii) The substituents in ortho position must have a large size.
Note: There is no chiral centre in Biphenyl, it is the molecule as a whole which is chiral, due to restricted
rotation. The chirality due to restricted rotation arround CC single bond in biphenyl is known as atropisomers.
Remark: If H, F and OCH3 group are present on ortho position of biphenyl then rotation of the ring will not
be prevent. Because the volume of these groups are too small to prevent the rotation about the single bond.

Cl

Me
O2N

HOOC

Cl

NO2

O2N

COOH

Cl

O2N

O
NO2

COOH

Br
Properly substituted
Restricted rotation
So optically active

Properly substituted
Restricted rotation
So optically active

Properly substituted
Restricted rotation
So optically active

Cl
H3C

H3C
Cl

CH3
Cl

Cl

NH2

H3C

CH3

CH3
Properly substituted
Not restricted rotation
So optically inactive

HO3S
H

H
SO3H
Optically active

Not properly substituted

Restricted rotation
Optically inactive

t-Bu

t-Bu
Optically active
t-Bu is bulky

Br
Achiral (restricted rotation
But not properly substituted)
Optically inactive

58

Stereochemistry

Some more examples of biphenyl type compounds are as follows:

HOOC
CH3

HOOC

HOOC

(1)

H3C
N

(2)

COOH
CH3

CH3

COOH

CH3

H3C

COOH

COOH

(3)

C6H5

C6H5

(4)

COOH

N
COOH

COOH

COOH
COOH

(5)

(6)
COOH

COOH

H3C

(7)

NO2
Properly substituted but
not ristricted rotation.So,
optically inactive.

(8)
N

H3C

COOH

R/S in Biphenyl:

Cl

HOOC
HOOC

2
3

NO2

CH3

Br
S-Isomer

Put the head of the arrow on which side

where configuration of the ring is defined in
the problem and then assign priority sequence
as per CIP rule.

59

Stereochemistry

HO

HO

HOOC

O2N

R-Isomer

O2N

COOH

Me

Cl

S-Form

Me

Cl

NO2

O2N

COOH

4O

S-Isomer

COOH

CH3

S-Isomer

(B) Chirality in Allenes

Allenes are chiral due to chiral axis.
Essential criteria for chirality of allene.
(1) Proper substitution
(2) Number of double bond should be even.
Properly substituted means that terminal carbon of allene should have two different groups, so that it deprive
from plane of symmetry.
sp2
sp2
H

H
C

C
H

sp

symmetry element
3C2'S
2 v

Problem-1:
Cl

(1)

Cl

Cl
C

H
H
Number of double bond = even
Properly substituted
So it is chiral

(2)

Br
C

Cl
H
Number of double bond = even
Properly substituted.
So it is chiral.

60

Stereochemistry
Br

Br

H
C

(3)

F
Cl
Number of double bond = even
Properly substituted
So, it is chiral.

H
C

(4)

F
Cl
Number of double bond = odd
Properly substituted
Achiral, optically inactive.
Cl

Ph
C

(5)

CMe3

Ph
C

C C C C C

(6)

Me3C

COOCH2COOH

Br

Cl

Number of double bond = even

Properly substituted
Chiral, optically active.

Number of double bond = even

Properly substituted
Chiral, Optically active.

Note: One of the double bond of allene may be replaced by a four, five & six membered ring and the
general shape of the allene molecule is retained.
For such a system. Optically activity arises if Number of doubled bond + ring = even and criteria for
properly substitution is same.
H

Me
C
H

CO2H

1 double bond + one ring = 2 = even

Properly substituted
Chiral and hence optically active.
Problem-2:
H

H
C

CH3

(1) H3C

1 double bond + 1 ring = even

Properly substituted
Chiral, optically active.

Problem-3:
Br

CH3
C

*
chiral
centre

CH3
C

(2)

chiral

Br

CH3

2 double bond + 1 ring = odd

Properly substituted
It is chiral, due to chiral centre but not chiral axis.

2 double bond + 1 ring = odd

Properly substituted
Achiral, optically inactive.

61

Stereochemistry

R/S in allene.
2
H
C

(1)

Cl

3
Cl
C

Me3C
C

(2)

H
4

Me

1
HOOC

4
H
C

C
2

C
Cl
3

(3)

3
Me

R-form

H
4

S-Form

(C) Optical Activity in Spirane:

If both double bonds in allene are replaced by ring system, the resulting molecules are spiranes.
H

H
H

H
H

Examinations of these formulae show that the two rings are perpendicular to each other, and hence suitable
substitution will produce molecules with no element of symmetry, thereby giving rise to optically active forms.

1.
2.

Essential criteria for chirality due to chiral axis.

Even number of ring in spiro compound (Odd number of spiro carbon)
Proper substitution at only terminal H.
Spirane has two types of hydrogen
(1) Lateral
(2) Terminal.

H H

H
H

H
Terminal hydrogen

Terminal hydrogen
H

H
H

H H

Lateral hydrogen

4Hs are terminal, 8Hs are lateral.

Chirality due to chiral centre can be generated in any spirane compound (even or odd number of ring) by
substitution at lateral hydrogen (Plane of symmetry should not be there).
Chirality due to chiral axis can be generated in spiranes having even numbers of rings by proper substitution.
H

CH3

H3C

chiral
Number of rings = even
Properly substituted
Chiral due to chiral axis.

CH3

Number of rings = odd

Not properly substituted
But chiral due to chiral centre not due to axis.

62

Stereochemistry
H

H2N

NH2

Number of rings = even

Properly substituted
Chiral, due to chiral axis.

R/S nomenclature in spirane

Similar to allene and biphenyl.
3

H2

H2

CH3

3
NH2

R-Form

R-Isomer
H3C 1

H2N 1

4H

4H

Planar Chirality:
y

y
x

Fe

Fe

Specific type of chirality known as planar chirality.

Chirality can not be removed it is permanent.
View the molecule
from top.
2
CH2

NMe2
NMe2

H2C

Fe

PPh2

PS

Ph2P
1

Fe

PS

This 'P' stand for planar.

PR

Note:
*

NMe2

CH
Me

Fe
The side chain has a chiral centre such type of
chirality is called lateral chirality.

Conformational Analysis
Conformation studies of unsaturated compounds and compounds containing the oxo group have led to some
unexpected results. For example, microwave spectroscopy has shown that the preferred conformation of
propene and acetaldehyde are the eclipsed forms and NMR spectroscopy has shown that the predominant
conformation of propionaldehyde is the one in which methyl group and oxygen atom are eclipsed. The reason
for these observation is uncertain.

63

Stereochemistry
O
H3C

C
H

CH2
H3C

C
H

CH2
H

H
Propene

H3C
H

CH2

Propionaldehyde
CH3

H
H
Acetaldehyde

H
H

Propionaldehyde

Remark: Molecule such as ethylene chlorohydrin or ethylene glycol, intramolecular hydrogen bonding is
possible in the skew form but not in the staggered form, due to this intramolecular H-bonding the molecule is
stabilised by about 20-29 kJ/mol and this is enough to make the skew form more stable than the staggered
form.

EvidencesI.R. spectroscopy has shown that the skew form predominates.

H

Intramolecular H-bonding
O

O
H
H

Cl
H

H
Gauche form of ethylene chlorohydrine

H
Gauche form of ethylene diol

Method used to investigate the conformation of molecules.

Thermodynamic calculation
Dipole moment.
X-ray and electron diffraction
IR and UV spectroscopy
Chemical method.
NMR spectroscopy

Conformational Analysis of Cyclohexane

Factor affecting the stability of conformations
(1) Angle strain: Any deviation from normal bond angle
(2) Torsional strain: Any deviation from the staggered arrangement.
(3) Vander waals strain(Steric Strain):
Any two atoms (or group) that are not bonded to each other can interact in several ways depending on
(a) Their size
(b) Polarity
(c) How closely they are brought together.
These non bonded interaction can be either repulsive or attractive, and the result can be either destabilization
or stabilization of the conformation.
Bayer suggested (incorrectly) there should be certain amount of strain in cyclohexane.
Two most stable form of cyclohexane are as follows:

Chair form

Boat form

Chair form is more stable than that of boat form due to following fact.

64

Stereochemistry

Chair form
(1) No angle strain
(2) No torsional strain
(3) No flagpole interaction
(4) No any eclipsed ethane condition

Boat form
(1) No angle strain
(2) Torsional strain is present.
(3) Flagpole interaction is present (vander waal strain)
(4) Two eclipsed ethane condition (will creat torsional strain)

Conclusion: The boat conformation is less stable than the chair conformation.
Flagpole bond

boat conformation in
Newmann projection
formula.

Potential energy relationship among conformation of cyclohexane.

Stability order: Chair > twist boat > boat > half chair
Mono substituted cyclohexane:

1.6
kcal

2
11kcal

CH3
Equatorial

More stable
No. 1, 3-interaction

P.E.

5.5 kcal

CH3
axial
Less stable due to
1, 3-interaction

Half
chair

Twist
boat

boat

Remark: Except for H, a given atom or group has more room in an equatorial positions than the axial
position. Most molecule (about 99% at room temperature) exist in the conformation with methyl in uncrowded
equatorial position.
Disubstituted cyclohexane:
1, 2-disubstituted cyclohexane

Homo disubstituted

Hetero disubstituted cyclohexane.

Cis and trans relationship in disubstituted cyclohexane can be understood as

1, 2-disubstituted cyclohexane.
1, 4-disubstituted cyclohexane. 1, 3-disubstituted cyclohexane.
Cis (a, e) or (e, a)
Cis (a, e) or (e, a)
Cis (a, a) or (e, e)
Trans (a, a) or (e, e)
Trans (a, a) or (e, e)
Trans (a, e) or (e, e)
Let us consider an example of 1, 2-disubstituted cyclohexane.
CH3

CH3

Cis

CH3

CH3
CH3

(I) (a, e)

(II) (e, a)

CH3
CH3

Trans
CH3

(III) (a, a)

(IV) (e, e)

65

Stereochemistry

I & II are degenerate because both have one 1, 3-interaction.

III & IV are non degenerate
III is least stable because in this case both methyl group is placed at axial position and suffer 1, 3-interaction.
So, the stability order is IV >I > II > III
1, 2-disubstituted cyclohexanes with two different substituents.
Let us consider an example of 1-ethyl-2-methyl cyclohexane.
Cis-isomer

Trans-Isomer

Me

Me
Me

Me
Et

Et
Et

(1) (a, e)

Et

(2) (e, a)

(4) (a, a)

(3) (e, e)

1 and 2 are non degenerate.

Remark: Energy of conformation (2) will greater than that of (1) because, the bulky ethyl group is at axial
position which suffer more 1,3-interaction.
Me
H
Et

3 and 4 are also non degenerate, out of these two conformations, (4) has maximum energy because both,
methyl and ethyl are placed at axial position where they suffer severe 1, 3-interaction.
So, overall stability order is 3 > 1 > 2 > 4.
Optical activity:
CH3

CH3
Et

Et

Et

A pair of enantiomer

Et

H3C

A pair of enantiomer
CH3

1, 3-disubstituted cyclohexanes (1, 3-dimethyl cyclohexane)

Cis-1, 3-dimethyl cyclohexane.
H3C
Me
Me
(1) (a,a)

Trans-1, 3-dimethyl cyclohexane.

CH3

(2) (e,e)

Me
Me

(3) (e,a)

H3C

(4) (a,e)

CH3

3 and 4 are degenerate.

1 and 2 are non degenerate.
Energy order 1 > 3 ~ 4 > 2.
Stability order 2 > 3 ~ 4 > 1
Note: In Cis-1, 3-dimethyl cyclohexane, plane of symmetry is present in both (a, a) or (e, e) conformation.

66

Stereochemistry

Plane of symmetry

CH3

CH3

H
Me

Me

H
CH3

(a, a)
CH3

However, trans 1, 3-dimethyl cyclohexane, does not have a plane of symmetry and exist as a pair of enantiomers.
Let us consider the case of 1-isopropyl-3-methyl cyclohexane.
cis-1-isopropyl-3-methyl cyclohexane.
trans-isoprophyl-3-methyl cyclohexane.
Me

Me

Me

i-Pr

Me

i-Pr

i-Pr

(3) (a, e)

(2) (e,e)

(1) (a, a)

(4) (e, a)

i-Pr

1 and 2 are nondegenerate.

3 and 4 are non degenerate.
Stability order:

2>3>4>1

Both group at axial position

Bulkier group (i-Pr) at axial position.
Both group at equitorial position

Let us consider an example of 1,3-dihydroxy cyclohexane.

Cis-1,3-dihydroxy cyclohexane.
trans-1, 3-dihydroxycyclohexane.

HO
OH

OH

(1) (a, a)

OH

OH

(2) (e,e)

OH

(3) (a,e)

HO

(4) (e,a) OH

Stability order 1 > 2 > 3 ~ 4

Conformer (1) is more stable than that of (2) because of the fact that in case of (1) intramolecular H-bonding
is possible.

O
H

O
H

Intramolecular H-bonding.

67

Stereochemistry

PROBLEMS
1.

From which conformation of cis-1, 3-cyclohexane dicarboxylic acid anhydride will be form.
COOH
COOH

Ring flip

COOH

COOH
(S)

(A)

Cis-cyclohexane 1, 3-dicarboxylic acid

Soln. Cis-cyclohexane-1, 3-dicarboxylic

diaxial conformer(Less stable)

acid diequatorial conformer

(More stable)

Anhydride
Remark: The COOH grop in (A) are far apart for anhydride formation. Ring flip to give (S) brings them with
in reacting distance.
2.

Draw the favoured conformation of following compounds

OH

OH Me

OH

Br

Br

i-Pr

(1)

(2)
OH

Soln. (1)

Br
Br
OH
Br

favour

Two substituents
equatorial (non-axial)

OH
No substituents equatorial
two (axial).

OH

(2)

Br
Br
favoured

OH

Me

Me

(3)

Since Br > OH (in size)

HO

Br

OH
i-Pr
OH
i-Pr

Favoured
Two substituents equatorial one axial.

i-Pr
Me
OH
One substituent equatorial two axial.

68

Stereochemistry

1, 4-disubstituted cyclohexane: Let us consider an example f 1, 4-dimethyl cyclohexane.

Cis-1, 4-dimethylcyclohexane.

trans-1, 4-dimethylcyclohexane.

Me

Me

Me

Me

(1) (e,a)

Me

Me

(3) (e,e)

Me (2) (a,e)

Me

(4) (a, a)

Stability order: 1 > 1 ~ 2 > 4.

SOLVED PROBLEMS
1.

Draw the most stable conformation of cis-1, 4-di t-butylcyclohexane.

t-Bu
t-Bu

t-Bu
t-Bu

Soln.

t-Bu
t-Bu

Remark: An axial t-butyl group is very unfavourable form. In Cis-1,4-di-t-butyl cyclohexane, one t-butyl
group would be forced axial if the compound existed in a chair conformation, to avoid this, the compound
prefers to pucker into a twist boat so that the two large groups can both be in equatorial positions (or
Pseudoequatorial, since this is not a chair).
2.

Draw the most stable configuration of

CH3
Et

Me

OH

t-Bu

Me

t-Bu

OH

i-Pr

CH3

Soln.

i-Pr

Me
t-Bu

Me

t-Bu

OH

Et

OH

Remark: The bulky t-butyl group is particularly prone to occupy an equatorial position if other substituents
are considerably smaller than t-butyl, the molecule is virtually locked in a single conformation. The one with an
equatorial t-butyl group. t-butyl group has been widely used as a holding group to permit the study of physical
and chemical properties associated with a purely axial or purely equatorial substituent.
3.

The most stable conformation of the following compound is:

Me
Me

t-Bu

(a) t-Bu

Me
Me

Me

(b) t-Bu
Me

Me

(c) t-Bu

(d)
Me

Me

t-Bu
Me

69

Stereochemistry

Me

Ans.

t-Bu

. Because t-butyl group is locking group.

Me

4.

The favoured vicinal diols shown below only three are cleaved by HIO4. The diol which is not cleaved HIO4 is:
OH

OH

(a)

(b)
t-Bu

OH

t-Bu

OH

OH

OH

(c)

(d)
t-Bu

OH

t-Bu

OH
OH

OH
t-Bu

t-Bu

OH

Soln.
(a)

OH

t-Bu

OH

(b)

OH

OH
OH

t-Bu

(c)

(d)

(a) Because in this case the two-OH groups are diaxial, so there is more distance between two OH groups and
hence will not interact with HIO4 effectively.
5.

Accouts for the fact that only one of the following compounds A and B give the expected elimination product
with KI acetone.
Br

t-Bu

Br

Br

Br

t-Bu

(B)

(A)
Br
t-Bu

Br

t-Bu

Soln.
Br

Br

(A)

(B)

(A) will give the expected elimination product with KI in acetone because for E2-elimination. The two departing group should be placed at diaxial position (or antiperiplanar) such requirement is only fulfilled by compound
(A).
6.

Which of the following is a cis-isomer?

Me

(a)

Me
(b)
Me

CH3

(c) H3C

(d)

CH3

Me

Soln. (c) Because in case of 1, 3-disubstituted cyclohexane cis means (e, e) or (a, a).

CH3

70
7.

Stereochemistry

The stable form of trans-1,4-dimethyl-cyclohexane is represented as

CH3

CH3

(a) H3C

(b)
CH3

H3C

(c) H3C

(d)

CH3

CH3

Soln. (c) because both groups are at equatorial position.

8.
Identify the hydroxycyclohexane carboxylic acid, which upon heating readily gives a bicyclic lactone
COOH
COOH
CH3

(a)

(b)
CH3

OH

(c)

(d) HO

COOH

COOH

Soln. (d) Because after filiping of the ring the two groups OH and COOH come nearer to each other.
O

OH

O
COOH

HO

Lactone

COOH

9.

No one conformation will give this geometry.

Menthyl chloride (A) and neomenthyl chloride (B) both react with base to lose a molecule of HCl by E2
mechanism. The products are regio isomers (C) and (D). Identify which product is formed from which starting
compound. Also mention starting compound (A) or (B) which will react faster. Give reasons for your answer.

Cl

Cl

Cl
Me

Soln.

Me

Cl

H1

(A)

(B)

H2

In case of (B) for elimination of HCl with base Cl have diaxial relationship with H1 and H2 which is the demand
of E2 elimination.
Cl
Me

Me

C2H5OH1
H2

C2H5O

H1

71

Stereochemistry

If proton H2 will remove by base such as:

Cl
Me

This product will also obtain but more

highly alkylated product (C) will be formed.

C2H5O
H1

H2

In the chair conformation (A) Clatom is equatorially placed and we know for E2 elimination. The two departing group should be antiperiplanar, on this demand the conformation flip will occur such as
Me

H
C2H5O

Me

Less stable

Cl
Cl

More stable

So,

10.

Cl

Me

Me

Cl

Rate of elimination of (B) is faster than that of A because elimination of (A) occur from high activation energy
conformation.
How would you explain the addition of HI to tiglic acid (A) and angelic acid (B) to give stereospecifically the
erythro and threo--Iodo acid, (c) and (d) respectively instead of a mixture of both the acids (c and d) in each
case?
Me

COOH

Me

HI
CHCl3
Me

COOH

Me

H
H erythro (c)

Me

COOH

Me
HI
CHCl3

Me

Me

Soln.

Me

Me

Me
COOH

COOH

Me
H

Me

Me

H
Me

H
H

Me

COOH

COOH

H
COOH

Me

COOH

Me

Me

Me

I
erythro product

COOH

72

Stereochemistry
COOH
COOH
Me

Me

H
H

Me
Me

Me

H
I COOH

Me
I

I
Me
Me

H
H

Me

COOH

Me

H
H

I
COOH

I
COOH

Me

COOH

Me

Me

HOOC Me

Me

HOOC
I
H
Me

H
Me

COOH
H
Me
Me
H

Me
HOOC
H

Me

H
I

I
threo product only

Me

Conformation in six membered rings containing hetero atoms

In six membered ring containing hetero atoms, the basic principles are the same i.e. there are chair, twist and
boat forms, axial and equatorial groups etc, but in certain compounds a number of new factors enter the
picture.
For example:
In 5-alkyl-substituted 1, 3-dioxane, the 5-substitutent has a much smaller preference for the equatorial position
than in cyclohexane derivatives.
O

H
5

O
3

This indicate that lone pairs on the oxygen have a smaller steric requirement than the CH bonds in the corresponding cyclohexane derivatives.
+
Similar behaviour is found in the 1, 3-dithiane with certain nonalkyl substitution (eq, F, NO2, SOMe, N Me3)
the axial positions is actually preferred.
F

NO2

S
S

Preferred form

11.

Preferred form

Cisand trans2methyl 5-tbutyl1, 3-dioxane each can exist as two conformers as shown below.
O
O

C(CH3)3

H3C
O

CH3

cis-P

cis-Q

C(CH3)3

73

Stereochemistry

CH3
O
H3C

C(CH3)3

trans-R

trans-S C(CH3)3
The preferred conformations for the cis and transcompounds will be
(a) P, R
(b) Q, S
(c) P, S
Soln.

(d) Q, R

(b)
Hints: In Q the bulky group (t-butyl) does not suffer 1, 3-interaction because carbon is replaced by oxygen.
Conclusion: In heterocyclic rings the steric repulsion for axial substituents are reduced due to the replacement
of methylene groups of cyclohexane by oxygen or nitrogen.
OH

12.

Draw the most stable conformation of

O
O

H
O

Soln.
H

The presence of an oxygen atom in the ring allows hydrogen bonding that can stablize hydroxyl groups in the
axial position.

Specific Rotation
Specific rotation as optical rotation of I gm/mL concentrated solution when path length 10 cm (1 dm) at
particular wavelength (l) of light.

c.

Note: Most values are quoted as D (where the D indicates the wavelength of 589 nm, the D line of a
20

sodium lamp) or D , the 20 indicating 20 C .

Enantiomeric Excess
Enantiomeric excess or e e is a measure for how much f one enantiomer is present compared to the other.
For example, in a sample with 40% e e in R, the remaining 60% is racemic with 30% of R and 30% of S so that
the total amount of R is 40% + 30% = 70%.

% optically purity =

obs
100
max

assuming a linear relationship between and concentration, which is true for most cases. The optical purity
is equal to percent excess of one enantiomer over the other
So,

R S
Optical purity = percent enantiomeric excess R S 100 %R %S

Optical rotation

ee
specific rotation
100

74

Stereochemistry

13.

20 mg mandelic acid was dissolved in 1 cm3 of ethanol and the solution placed in a 10 cm long polarimeter
cell. An optical rotation of 4.35C was measured (that is, 4.35 to the left) at 20C with light of wavelength 589 nn. What is the specific rotation of the acid?

Soln.

20

Since, 4.35
10 cm 1 dm

c 28 mg / cm 3
c 28 103 g / cm3
c 0.028 g / cm3

4.35

155.4
c 0.028 1
So, the specific rotation of mandolic acid = 155.4.
20

So, D

14.

Calculate the optical rotation from the given data

sp 20
D = 90%
L = 10%
Soln. e e = 90% 10%
e e = 80%
So, Optical rotation
ee

15.

Soln.

80
20 16
100

Optical rotation
100
specific rotation

Calculate enantiomeric excess from the given data

sp rotation = 20
optical rotation = 18
18
100
20
e e = 90%
ee

Since, % of d % 100
% of d % 90 e e
So,

% of 2d 190

of d

190
95% & % 5%
2

Optical activity of compounds having symmetric carbon

Case I: If the molecule has no plane of symmetry and molecule has n asymmetric carbon atoms then
Number of optically active forms = 2n = a
Number of enantiomeric pair = a/2
Number of racemic mixture = a/2
Number of meso form = 0
Case II: If the molecule has plane of symmetry, then the number of configuration isomers depend on the
number of asymmetric carbon atoms.

75

Stereochemistry

(1) When compound has even number of asymmetric carbon atoms i.e. n = 2, 4, 6, ...........
(a) Number of optically active forms = a = 2n1.
(b) Number of enantiomeric pairs = a/2
(c) Number of racemic mixture = a/2
n

(d) Number of meso forms m 2 2 .

(e) Total number of configurational isomer = a + m
For example:

HOOC

CH(OH)

CH(OH)

COOH

n=2
Number of optical isomer a 2n 1 2
n

Number of meso form m 2 2 1 2 2 2 1 1 1

Total number of configurational isomers = 2+1=3
Let us consider another example
Ph

CHCl

CHCl

CHCl

CHCl

Ph

n= 4
a 241 23 8

m 2 2 2 2 1 221 21 2
So, the total number of configurational isomers 8 2 10
Case III: When compound has odd number of asymmetric carbon atoms and plane of symmetry
i.e. n = 3, 5, 7, 9, 11...........
(a) Number of optically active forms
n

a 2n 1 2 n 1 /2
(b) Number of enantiomeric pair = a/2
(c) Number of racemic mixture = a/2
(d) Number of meso forms = m = 2 n 1 /2
(e) Total number of configurational isomers = a + m.
For example:
*

HOH2C

CHOH

CHOH

*
CHOH

CH2OH

n=3

a 2n 1 2 n 1 /2 231 231/2 22 21 2 2 2 4 2 2
m 2

n 1 / 2

m 231/2 21 2
Hence total number of configurational isomers = 2 + 2 = 4

Number of Geometrical Isomers in Polyenes

(a)

When compound has n doube bonds and ends of polyene are different, the number of geometrical isomers =
2n .
where n = Number of double bonds.
Ph CH CH CH CH CH CH CH CH Cl

76
(b)

Stereochemistry

n=4
When the ends of polyene are same
Case I: When number of double bond is even.
Then the number of geometrical isomers.
n

2n 1 2 2 1
Let us consider another example
Cl CH CH CH CH CH CH CH CH Cl
n=4
n

Number of geometrical isomers 2n 1 2 2 1 23 21 8 2 10

Case II: When the number of double bonds are odd
Number of geometrical isomer 2n 1 2n 1/2

Ph CH CH CH CH CH CH Ph
Number of geometrical isomers 22 2

31
2

22 21 = 4 2 6

Topocity :
Topocity is the strereochemical relationship of substituents relative to the structure to which they are attached,
depending on the relationship, such groups can be heterotopic, homotopic enantiotopic, or diastereotopic.

Homotopic:
Homotopic atom, are always identical in any environment.
Homotopic NMR - active nuclei have the same chemical shift in an NMR spectrum.
eq CH4 all 4Hs are potential. So homotopic with one another.
Enantiotopic:
H

CH3

H3C

Br

C
H2

CH3

H3C

C
H2
R-2bromobutane

Butane

Br

CH3
C
H2
(S)2bromo butane
H3C

Enantiotopic groups are identical and indistinguishable except in chiral environment

Enantiotopic pairs of NMR active nuclei are also indistinguishable by NMR and produce a single signal..........
Diastereotopic groups are often, but not always identical group attached to the same atom in a molecule
containing at least one chiral centre.
Br

Br

C
H

CH3

H3C

enantiotopic face
F

Cl

CH3
Br

(2S,3R)2,3dibromobutane

C
C

H3C

(S)2bromobutane

Br

H3C
Br

CH3
H

(2S,3S), 2, 3dibromobutane

77

Stereochemistry

diastereotopic

Cl

Cl

3 singnal in NMR
H

enantiotopic
Hb

Ha

Br

NBS
(PhCO)2

Br

+
enantiomers
COOH
CH2
HO

COOH

CH2
COOH
Citric acid

Citric acid has the prochiral centre the two chain CH2COOH are enantiotopic.
This is an interesting example where enantiotopic and diastereotopic H, co-exist.
COOH

HO
HOOC

COOH

Ha

Ha
Hb

Hb

A plane of symmetry perpendicular to the page and passing through the middle carbon make Has enantiotopic
and Hbs also enantiotopic. No Plane of symmetry can pass between each CH2 group protons a and b on each
CH2 group diastereotopic.
Prochirality: Prochirality is the property of certain molecules due to which these can be converted into stereoisomers. (enantiomers or diastereoisomers).
COOH
Ha

Hb

CH3
Propionic acid

Non stereogenic centre.

78

Stereochemistry
2
COOH

COOH
Hb

Ha

COOH

3
H

OH

HO

4 CH3

CH3

R-lactic acid

S-lactic acid

CH3

Homotopic ligands and Faces:

If the substitution of each one of them by another atom or group leads to the same structure.
COOH
Ha/D
COOH

D
HO

OH
H

Hb

OH

COOH

HO

Ha

COOH

COOH

H
Hb/D

OH

HO

D
COOH

So, two hydrogens Ha and Hb are homotopic through rotational around

Hb

COOH
HO
Hb

OH

HO

Ha

OH

Ha

HO
COOH

C2

Problem:
O
H3C

OH

COOH
all 3H are identicals, so homotopic in nature

C3

Homotopic face:
CH3

H3C
C

H3C
C

C
H

C2-axis

CH3

C
H

OH

COOH
COOH

COOH

COOH

Ha
Hb

79

Stereochemistry
O
O

H1

H2

H2

C2

H1

homotopic face

homotopic face

Enantiotopic ligand and faces

H1/D
COOH

3
S COOH
1
4
D
OH
2
OH
R
COOH (2S, 3R)

H2

H1

OH

H2

OH
COOH
H

COOH
1
OH
2
OH
R

COOH

These two are not non super imposable mirror images to each other but still diastereoiomers.

H2

OH

H1

OH

COOH

H1 and H2 are reflected by a plane

So, these two are enantiomers to each other.

COOH
H1

H2

H3C

CH3

H1/H2 are homotropic becaue it is

interchanged with C2-symmetry.

H
enantiotopic

HOH2C

OH

HOH2C

Cl
H2
Cl

Cl
H1

H1/H2 are enantiotopic

Cl

Diastereotopic ligands and faces:

80

Stereochemistry

H3C

Ha/Cl

Cl
C

H3C

Ha

So, these two are diasteroismers

cis(z)
C

trans (E)

Hb

H3C

H
C

C
Cl

HO
HO

HO

Ha

Ha/OH

Hb/OH

H
Hb

HO

Ha

H
OH trans

Hb
So, Ha and Hb diastereoisomers
CH3

Cl

Ha

Hb

Cl

Hb

Ha

CH3
Cl

Cl

So, Ha and Hb are diastereotopic.

CH3
CH3
H

Cl

Ha

Hb

Cl

Br

Hb
Cl
CH3

Cl

Cl

Ha

Br
Cl

Diastereotopic face:
CH3

CH3

CH3

C O
H3C

HCN

CN

OH

H3C

C6H5

CN

H3C

H
C6H5

C6H5

Methyl -phenethyl ketone

O
t-Bu

HO

NaBH4

OH
OH + t-Bu

t-Bu
trans

So this face is diasterotopic

H
cis

81

Stereochemistry

PROBLEMS
Hb

Ha

1.

So, Ha/Hb are diasrereoisomers because it is

bisected from a plane.

CH3

H3C

H3CH2C

2.

diastereotopic

(i)

OH

H3C

diastereotopic

(ii) t-Bu
1
O

O1

O
3

2
H3C
3

CH3
Se-face

H3C

CH2CH3
Re-face

Re-face

CH3
diastereotopic since there is no symmetry and the
two methyl group are close to a stereogenic centre.

3.
CH
H3C

CH3

CH2OH

H3C
diastereotopic when the rotation of the ring is slow when rotation becomes
fast these protons become enantiotopic (average mirrorplane)

CH3 H

*
OH

4.

Indicate Ha and Hb are homotopic, enantiotopic or diastereotopic.

Ha

Hb

Ha

Hb
H3C

(1)
homotopic

diastereotopic replacement test

would give syn and anti compounds
which are diastereomers.

H2
C

Hb

Ha
C

Ha

CH3

Hb
enantiotopic

homotopic

82

Stereochemistry

Let us consider an example of norborane system first we want to discuss the symmetry properties of this
system.
H1 1 H2
H13
H3

H9

7
H7

H10

5
H12

H4
H5

4
H6

H8

It has one C2 axis passing through C1 and interchanging C2/C5, C3/C6, C4/C7. H1/H2, H12/H13, H3/H7, H5/H9,
H4/H8, H6/H10.
So, these protons are identical (as we know the protons which are interchanging with an axis are identical i.e.
homotopic protons).
Now, It has two v.
(a)

v1bisecting C1C2C5, H13, H12 reflecting C3/C7, C4/C6, H1/H2, H3/H9, H5/H7, H6/H8, H4/H10.

(b)

v2bisecting C1, H1, H2 and reflecting C2/C5, C3/C4, C7/C6, H13/H12, H3/H5, H4/H6, H9/H7, H10/H8.
The protons which are reflected with plane are enantiotopic where as those which are bisected with plane are
diasterotopic.
Note: If a protons are interchanging with C2 axis and also reflected by plane the priority will be given to
interhanging by axis and hence it will be homotopic but not enantiotopic.
For example
H1

H2

H1/H2 are interchangabe with C2-axis and also reflected by a plane. So, in this case priority will be given to
former not latter and hence H1/H2 are homotopic proton.
5.

Identify the correct stereochemical relationship amongst the hydrogen atoms Ha, Hb and Hc in the following
molecule.
[GATE-2006]

Hc

Hb
Ha

(a) Ha and Hb:enantiotopic

(c) Ha and Hc: enantiotopic

(b) Ha and Hb : diastereotopic

(d) Hb and Hc : diastereotopic

Soln. Since, Ha and Hb do not have direct relationship with any symmetry element. So, we will have to see chemical
environment around Ha and Hb since the chemical environment is different viz Hb is exo where as Ha is endo so
these protons are diastereotopic.
Hc/Hb are reflected with plane hence it will be enantiotopic.
Ha/Hc diastereotopic
Correct answer is (b)

83

Stereochemistry

6.

The two Hs at C2 and C3 in (2R, 3S) tartaric acid.

(a) enantiotopic
(b) diastereotopic
(c) homotopic

(d) constitutionally heterotopic

COOH
H

OH

OH
COOH

Soln. These two hydrogenes are reflected by a plane.

So, it is enantiotopic.
H

7.

Cl
H1

H2

Cl

The relation between H1/H2 are

(a) Homotopic
(b) Diastereotopic
(c) enantiotopic
Soln. Since H1 and H2 are interchangable with C2-axis so these two are homotopic.
8.

CSIR-JRF-2008

Consider the hydrogen atoms labelled as HA and HB in the following molecules. [IAS-2008 ]
CH3

COOH
H3C
C

(1)

HA

HA
C

HB

HB

OH

HA

(3)

(2)

OH

Br

HB

HA

OH

CH3

COOH

(4)
HB

R
H
R

In which of the above are HA and HB diastereotopic

(a) 1, 2 and 3
(b) 2, 3 and 4
(c) 1, 3 and 4
(d) 1, 2 and 4
Soln. (b) have plane of symmetry so HA and HB are enantiotopic in the case of (3). HA and HB are adjacent to the
chiral centre so these two protons are diastereotopic while in case of (4) no direct relationship with symmetry
element while chemical environment of these two protons are different so these two are diasterotopic.
So, the correct answer is (c)
9.
Consider the following molecule S:
[IAS-2007]
1. trans-1, 2-dichlorocyclo propane.
2. cis-1, 2-dichlorocyclo propane
3. 1, 1, 2-trichlorocyclopropane.
In which of the above molecules is/are the sets(s) of methylene hydrogen(s) diasterotopic?
(a) 1 only
(b) 1 and 3
(c) 2 and 3
(d) 2 only
H

Soln. H

H
Cl

Cl

Cl

Cl

Cl

Cl
Cl

1.
2.
3.
In case of (1) the methylene Hs are exchangable with C2 symmetry so, these two are homotopic while in (2)
methylene protons are bisected with a plane so these two are diastereotopic
I n case of (3) No methylene protons are present.
So, correct answer is (d).

84
10.

Stereochemistry

Consider the following compounds.

Ha

Ha
H

Ha

Br

H3C

H2
C

Hb

CH3

Hb

Hb

III
II
I
Identify Ha and Hb hydrogens in the above compounds.
(a) diastereotopic, enantiotopic, homotopic respectively.
(b) Enantiotopic, diastereotopic, homotopic respectively.
(c) Homotopic, diastereotopic, diastereotopic respectively.
(d) diastereotopic, enantiotopic, diastereotopic respectively.

Soln. (a)
H

Br

11.

C
CH3

Ans.

[IAS - 2006]

What are the two methylene protons in the above compound called?
(a) Homotopic protons
(b) Tautomeric protons
(c) Diastereotopic protons
(d) Enantiotopic protons.
(c)
HA

HB

12.
HC

HF

HD HE

Consider the following statements concerning the features of the protons of the structure given above
1. HA and HB are homotopic
3. HE and HF are diastereotopic
2. HC and HD are enantiotopic
4. HC and HE are vicinal and cis.
Which of these statements are correct?
(a) 1 and 2
(b) 2 and 4
(c) 1, 2 and 4
(d) 2, 3 and 4
[IAS-2003]
Soln. HA and HB are homotopic because they are exchanged with C2-axis.
HC and HD are enantiotopic because they are reflected with a plane.

13.

HE and HF are not diastereotopic because they reflected with a plane but not bisected.
So, the correct answer is (c).
In the compound
HA

HB

H3C
Cl
H
Cl

The two hydrogen atoms marked as the HA and HB are

(a) enantiotopic
(b) diastereotopic
(c) homotopic
(d) anomer.
Soln. (b) because these two methylene protons are adjacent with chiral centre.

[IAS-2001]