Organic Chemistry
Physical Chemistry
Inorganic Chemistry
Texbooks
 Details in course handout
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Overview
 Detailed handout to be updated in course server
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General Chemistry – Chem F 111 Faculty
Lecture Instructors
Pr.of Subhadeep
Banerjee (IC)
Organic
Prof. Raghunath Behera
Physical
Prof. Bhavana P.
Inorganic
Tutorial Instructors
Dr. Subhasish
Roy
Prof. Rashmi
Chauhan
Prof. R.N.
Panda
Dr. Uttara Basu
Dr. Sudipta Chatterjee
Dr. Woormileela
Sinha
Dr. Jayadevan K. P.
Dr. Kiran Vankayala Dr. Saurav Bhattacharya
STEREOCHEMISTRY
5
Chapter Contents
 Types of isomerism
 Stereoisomers
 Chirality and biological significance
 R/S configuration
 Optical Activity
 Synthesis of Chiral molecules
 Multiple chiral centers
 Fischer projections
 Configurations and reactions
 Enantiomeric Resolution
 E/Z-configuration for olefins
6
Isomerism: Constitutional Isomers and Stereoisomers
7
OH
Constitutional Isomers
Constitutional isomers are isomers which have the same
molecular formula but differ in the way their atoms are connected
Stereoisomers
Stereoisomers are isomers with the same molecular formula and
same connectivity of atoms but different arrangement of atoms in
space
H OH
(I)
HO H
(II)
8
Stereoisomers
 Chiral molecules (possess molecular asymmetry)
 Enantiomers
•
•
•
Can exist as a pair of enantiomers with identical chemical
and physical properties
The pair possesses a non-superimposable mirror image
relationship
Ability to rotate plane polarized light in opposite
directions by each member of the pair
 Achiral molecules (possess molecular symmetry)
 Superposable on its mirror image
9
Chirality
Chiral molecules - generally molecules containing an
asymmetric or chiral center
Asymmetric (chiral) center - tetrahedral atom bonded to
four different groups - indicated with an asterisk (*)
10
Chiral vs Achiral
11
Test for Chirality: Planes of Symmetry

A molecule will not be chiral if it possesses a plane of
symmetry

A plane of symmetry (mirror plane) is an imaginary plane that
bisects a molecule such that the two halves of the molecule are
identical

All molecules with a plane of symmetry possess identical
halves on either side of the plane and thus are achiral
Ch. 5 - 12
Plane of symmetry
Cl
Me
Me
H
achiral
Cl
Me
Et
H
No plane of symmetry
chiral
Ch. 5 - 13
Chirality and Biological Significance
Chiral objects are objects with left-handed and right-handed forms
Achiral objects - objects that have superimposable mirror images
Nonsuperimposable mirror images - a mirror image that is not the same as the
image itself - chiral objects have nonsuperimposable mirror images
14
Examples from real life
Ajino moto =
MSG
Thalidomide
15
Thalidomide
 The activity of drugs containing chirality centers can vary
between enantiomers, sometimes with serious or even
tragic consequences
 For several years before 1963 thalidomide was used to
alleviate the symptoms of morning sickness in pregnant
women
 In 1963 it was discovered that thalidomide (sold as a
mixture of both enantiomers) was the cause of horrible
birth defects in many children born subsequent to the use
of the drug
Ch. 5 - 16
Naming Enantiomers: R,S-System
Recall:
OH
H
(I)
OH
HO
H
(II)

Using only the IUPAC naming that we have
learned so far, these two enantiomers will have
the same name: 2-Butanol

This is undesirable because each compound
must have its own distinct name
Ch. 5 - 17



How to Assign (R) and (S) Configurations
Rule 1
● Assign priorities to the four different groups on the
stereocenter from highest to lowest (priority bases on
atomic number, the higher the atomic number, the higher
the priority)
Rule 2
● When a priority cannot be assigned on the basis of the
atomic number of the atoms that are directly attached to
the chirality center, then the next set of atoms in the
unassigned groups is examined. This process is continued
until a decision can be made.
Rule 3
● Visualize the molecule so that the lowest priority group is
directed away from you, then trace a path from highest to
lowest priority. If the path is a clockwise motion, then the
configuration at the asymmetric carbon is (R). If the path is
a counter-clockwise motion, then the configuration is (S)
Ch. 5 - 18

Example
①
Step 1:
② or ③
H
O
H
C
①
Step 2:
HO
H3C
④
C
H
O
③
(2-Butanol)
② or ③
④
C ② CH
3
C
H2
(H, H, H)
(C, H, H)
Ch. 5 - 19
①
④
③
OH
OH
Me
Et
②
Et
Me
OH
OH
Me
H
HO
Et
Me
H
Et
= H
Arrows are clockwise
Et
Me
(R)-2-Butanol
Ch. 5 - 20

Other examples
①
Cl
④
Cl
③
H
HO
CH3
HO
Counterclockwise
CH3
(S)
②
②
④
H 3C
① Br
OCH3
③
CH2CH3
OCH3
Clockwise
(R)
Br
CH2CH3
Ch. 5 - 21

Other examples
● Rotate C–Cl bond such that H is pointed
to the back
②
Cl
Cl
④
Br
HO
H
③
H
OH
① Br
Cl
Br
Clockwise
OH
(R)
Ch. 5 - 22

Other examples
● Rotate C–CH3 bond such that H is
pointed to the back
②
H
I
H3C
OCH3
④
OCH3
①
H
I
H3C ③
Counter-clockwise
H 3C
OCH3
I
(S)
Ch. 5 - 23

Rule 4
● For groups containing double or triple bonds, assign
priorities as if both atoms were duplicated or triplicated
e.g.
C O
as
C O
O C
C C
as
C C
C C
C C
as
C C
C C
C C
Ch. 5 - 24

Example
③
④
CH3
②
H
HO ①
Compare
CH3
&
CH CH2
Thus,
CH3
(S)
CH=CH2
CH CH2 :
equivalent to
H H
C C H
C C
 (H, H, H)
CH CH2  (C, C, H)
Ch. 5 - 25

Other examples
②
(R)
OH
④
H
③ CH3
Cl ① O
③
H 2C
④
H
①C l
O H
② CH 3
O
(S)
② C  (O, O, C)
③
C  (O, H, H)
Ch. 5 - 26
Properties of Enantiomers

Enantiomers
● Mirror images that are not superposable
H
Cl
H3CH2C
H
*
*
CH3
H3C
Cl
CH2CH3
mirror
Ch. 5 - 27

Enantiomers have identical physical properties (e.g.
melting point, boiling point, refractive index,
solubility etc.)
Compound
bp (oC)
(R)-2-Butanol
99.5
(S)-2-Butanol
99.5
mp (oC)
(+)-(R,R)-Tartaric Acid
168 – 170
(–)-(S,S)-Tartaric Acid
168 – 170
(+/–)-Tartaric Acid
210 – 212
Ch. 5 - 28
Optical activity

The property possessed by chiral substances of rotating the
plane of polarization of plane-polarized light is optical activity

The electric field (like the magnetic field) of light is oscillating in
all possible planes

When this light passes through a polarizer (Polaroid lens), we get
plane-polarized light (oscillating in only one plane)
Ch. 5 - 29
Plane-Polarized Light
Polaroid
lens
Ch. 5 - 30
The Origin of Optical Activity
Two circularlypolarized beams
counter-rotating at
the same velocity (in
phase), and their
vector sum
Two circularly-polarized
beams counter-rotating
at different velocities,
such as after interaction
with a chiral molecule,
and their vector sum
Ch. 5 - 31
The Origin of Optical Activity
Ch. 5 - 32
The Origin of Optical Activity
Ch. 5 - 33
The Polarimeter

A device for measuring the optical activity of a chiral compound
a=
observed
optical rotation
Ch. 5 - 34
Specific Rotation
observed
rotation
temperature
25
[a]D =
wavelength of
light
(e.g. D-line of
Na lamp,
l=589.6 nm)
c
a
x
ℓ
concentration length of cell
of sample
in dm
solution
(1 dm = 10 cm)
in g/mL
Ch. 5 - 35
•
The value of a depends on the particular experiment (since
there are different concentrations with each run)
•
But specific rotation [a] should be the same regardless of
the concentration
Ch. 5 - 36

Two enantiomers should have the same value of specific
rotation, but the signs are opposite
CH3
CH3
*
H
HO
25
*
CH2CH3
[a] = + 13.5
D
o
H3CH2C
25
mirror
H
OH
[a] =  13.5
o
D
Ch. 5 - 37
Racemic Forms


An equimolar mixture of two enantiomers is called a racemic
mixture (or racemate or racemic form)
A racemic mixture causes no net rotation of plane-polarized light
equal & opposite
rotation by the
enantiomer
rotation
H
CH3
OH
C 2H 5
(R)-2-Butanol
H 3C
H
HO
C 2H 5
(S)-2-Butanol
(if present)
Ch. 5 - 38
Racemic Forms and Enantiomeric Excess

A sample of an optically active substance that consists of a
single enantiomer is said to be enantiomerically pure or to
have an enantiomeric excess of 100%

An enantiomerically pure sample of (S)-(+)-2-butanol shows
a specific rotation of +13.52
25
[a]D


= +13.52
A sample of (S)-(+)-2-butanol that contains less than an
equimolar amount of (R)-(–)-2-butanol will show a specific
rotation that is less than 13.52 but greater than zero
Such a sample is said to have an enantiomeric excess less
than 100%
Ch. 5 - 39

Enantiomeric excess (ee)
● Also known as the optical purity
% enantiomeric
=
excess
●
mole of one
enantiomer
moles of other
enantiomer
total moles of both enantiomers
x 100
Can be calculated from optical rotations
% enantiomeric
=
excess *
observed specific rotation
specific rotation of the
pure enantiomers
x 100
Ch. 5 - 40

Example
● A mixture of the 2-butanol enantiomers
showed a specific rotation of +6.76. The
enantiomeric excess of the (S)-(+)-2-butanol is
50%
% enantiomeric
=
excess *
+6.76
+13.52
x 100 = 50%
Ch. 5 - 41
The Synthesis of Chiral Molecules
Racemic Forms
CH3CH2CCH3 + H H
(
)-CH 3CH2CHCH3
OH
O
Butanone
(achiral
molecules)
Ni
Hydrogen
(achiral
molecules)
(
 )-2-Butanol
(chiral
molecules; but
50:50 mixture
(R) & (S))
Ch. 5 - 42
Ch. 5 - 43
Stereoselective Syntheses

Stereoselective reactions are reactions that lead to a
preferential formation of one stereoisomer over other
stereoisomers that could possibly be formed
● enantioselective – if a reaction produces
preferentially one enantiomer over its mirror
image
● diastereoselective – if a reaction leads
preferentially to one diastereomer over others
that are possible
Ch. 5 - 44
O
O
+
OEt
F
racemate ( 
)
O
OEt
F
racemate ( 
)
H , H2O
heat
OH + EtOH
F
racemate ( 
)
O
H2O
lipase
OH
F
()
(> 69% ee)
O
+
OEt + EtOH
F
(+)
(> 99% ee)
Ch. 5 - 45
Relating Configurations through Reactions in Which
No Bonds to the Chirality Center Are Broken

If a reaction takes place in a way so that no bonds to the chirality center are
broken, the product will of necessity have the same general configuration of
groups around the chirality center as the reactant
Ch. 5 - 46
Same configuration
O
Me H
Me
Ph
H
NaBH4
MeOH
NaCN
H
Br
DMSO
OH
H
H
Me H
Me
Ph
H
CN
Same configuration
Ch. 5 - 47
Molecules with More than One Chirality Center

Diastereomers
● Stereoisomers that are not enantiomers
● Unlike enantiomers, diastereomers usually have
substantially different chemical and physical
properties
Ch. 5 - 48
Br
Cl C H
HO C H
CH3
Br
H C Cl
H C OH
CH3
(II)
Br
C H
Cl
(III)
CH3 C H
HO
Br
H C Cl
H C CH3
OH
(IV)
(I)
Note: In compounds with n tetrahedral stereocenters, the maximum number of
stereoisomers is 2n.
Ch. 5 - 49
Br
Cl C H
HO C H
CH3
Br
H C Cl
H C OH
CH3
(II)
Br
C H
Cl
(III)
CH3 C H
HO
Br
H C Cl
H C CH3
OH
(IV)
(I)
(I) & (II) are enantiomers to each other
 (III) & (IV) are enantiomers to each other

Ch. 5 - 50
Br
Cl C H
HO C H
CH3
Br
H C Cl
H C OH
CH3
(II)
Br
C H
Cl
(III)
CH3 C H
HO
Br
H C Cl
H C CH3
OH
(IV)
(I)

Diastereomers to each other:
● (I) & (III), (I) & (IV), (II) & (III), (II) & (IV)
Ch. 5 - 51
Meso Compounds

Compounds with two stereocenters do not always have four
stereoisomers (22 = 4) since some molecules are achiral (not
chiral), even though they contain stereocenters

For example, 2,3-dibromobutane has two stereocenters, but
only has 3 stereoisomers (not 4)
Ch. 5 - 52
H
(I)
CH3 C Br
CH3 C Br
H
H
C Br
CH
3
(III)
H C Br
CH3
Br
Br
Br
Br
H
C CH
3 (II)
C CH3
H
H
C CH
3 (IV)
C H
CH3
Note: (III) contains a plane of symmetry, is a meso compound,
and is achiral ([a] = 0o).
Ch. 5 - 53
H
(I)
CH3 C Br
CH3 C Br
H
H
C Br
CH
3
(III)
H C Br
CH3


Br
Br
Br
Br
H
C CH
3 (II)
C CH3
H
H
C CH
3 (IV)
C H
CH3
(I) & (II) are enantiomers to each other and chiral
(III) & (IV) are identical and achiral
Ch. 5 - 54
H
(I)
CH3 C Br
CH3 C Br
H
H
C Br
CH
3
(III)
H C Br
CH3


Br
Br
Br
Br
H
C CH
3 (II)
C CH3
H
H
C CH
3 (IV)
C H
CH3
(I) & (III), (II) & (III) are diastereomers
Only 3 stereoisomers:
● (I) & (II) {enantiomers}, (III) {meso}
Ch. 5 - 55
How to Name Compounds with More than One
Chirality Center

a
2,3-Dibromobutane
H
Br
Br
2
● Look through C2–Ha bond
4
a④
① Br
C2: (R) configuration
C1
H
3
1
③
b
H
2
②
C3
(H, H, H) (Br, C, H)
Ch. 5 - 56
● Look through C3–Hb bond
H
Br
Br
a
2
1
CH3
b
①
4
③
H
3
CH3
b
H
Br
C4
3
④
②
C2
(H, H, H) (Br, C, H)
C3: (R) configuration
● Full name:
 (2R, 3R)-2,3-Dibromobutane
Ch. 5 - 57
Fischer Projection Formulas: a 2D visual representation
of a 3D structure
How To Draw and Use Fischer Projections
Fischer
Projection
HO
H 3C
Et
Br
COOH
Ph
COOH
COOH
Br
Ph
Br
Ph
Et
OH
Et
OH
CH3
CH3
Ch. 5 - 58
H
Me
COOH
Ph
H
H
H
Ph
OH
COOH
COOH
COOH
Fischer
Projection
Me OH
HO
H
HO
H
Me
H
Me
H
Ph
Ph
Ch. 5 - 59
Cl
H
H
H3C
Cl
H
Cl
CH3
H 3C
(I)
(2S, 3S)-Dichlorobutane

H
CH3
(II)
(2R, 3R)-Dichlorobutane
CH3
CH3
H
Cl
Cl
H
CH3
Cl
enantiomers
mirror
Cl
H
H
Cl
CH3
(I) and (II) are both chiral and they are enantiomers with
each other
Ch. 5 - 60
Cl
H3C
H
H
CH3
Cl
CH3
H
Cl
H
Cl
(III)
(2S, 3R)-Dichlorobutane


CH3
Plane of
symmetry
(III) is achiral (a meso compound)
(III) and (I) are diastereomers to each other
Ch. 5 - 61
Fischer to Sawhorse & Newman Projection
Formulae
OH
H
CH3
H
OH
Cl
H
CH2CH3
Cl
OH
H
H
CH2CH3
CH3
H
Cl
CH3
CH2CH3
View Fischer projection
Sawhorse projection
(eclipsed)
H
OH
Cl
H
CH2CH3
CH3
Newman projection
projection
(eclipsed)
Sawhorse projection
Staggered
CH2CH3
H
OH
H
Cl
CH3
Newman
(Staggered)
62
Separation of Enantiomers: Resolution

Resolution – separation of two enantiomers
O
e.g.
OH
R * R'
(racemic)
O
O
Cl
OMe
Ph CF3
(Mosher acid
chloride)
R
R'
OMe
CF3
Ph
(1
O
O
+
R
:
R'
OMe
CF3
Ph
1)
diastereomers
usually separable
either by flash column
chromatography or
recrystallization etc.
Ch. 5 - 63
The (E) - (Z) System for Alkene Diastereomers

Cis-Trans System
● Useful for 1,2-disubstituted alkenes
● Examples:
H
(1)
Cl
Br
H
trans -1-Bromo2-chloroethene
Ch. 7 - 64
vs
Br
Cl
H
H
cis -1-Bromo-
2-chloroethene
● Difficulties encountered for trisubstituted and
tetrasubstituted alkenes
e.g.
CH3
Cl
Br
H
Cl is cis to CH3
and trans to Br
Ch. 7 - 65
cis or trans?
● Examples
Cl
CH3
Br
H
 (E )-2-Bromo-1-chloropropene
Br
Cl
CH3
H
 (Z )-2-Bromo-1-chloropropene
Ch. 7 - 66
● Other examples
(1) Cl
H
2
1
Cl
H
(2)
Cl
Ch. 7 - 67
C1: Cl > H
C2: Cl > H
2
1
Br
(E )-1,2-Dichloroethene
[or trans-1,2-Dichloroethene]
Cl
(Z )-1-Bromo-1,2-dichloroethene
C1: Br > Cl
C2: Cl > H
● Other examples
Br
4
(3)
1
3
2
8
7
5
6
(Z )-3-Bromo-4-tert-butyl-3-octene
C3: Br > C
t
n
C4: Bu > Bu
Ch. 7 - 68
Compounds with Chirality Centers Other than Carbon
R4
R1
R3
Si
H
R2
R1
R4
R1
R2
Ge
R2
R2
R3
N
R3
X
R1
S
O
Ch. 5 - 69
Chiral Molecules That Do Not Possess a Chirality Center
P(Ph)2
(Ph)2P
P(Ph)2
(Ph)2P
(S)-BINAP
(R)-BINAP
enantiomers
Ch. 5 - 70