First Year Organic Chemistry

12 Lectures
Monday: 12-1 pm
Tuesday 10am-12 pm

Prof. Kumar Biradha

Room: 603
JCG-PCR Building
kbiradha@yahoo.com

Organic Chemistry (2nd Ed.):

P. Y. Bruice

Organic Chemistry:
Clayden, Greeves,
Warren, Wothers

A Guide Book to mechanism

in Organic Chemistry
P. Sykes
Chemistry: The Central Science
1780s…
Organic compounds: obtained from living sources
Inorganic compounds: obtained from nonliving sources.
Friedrich Wöhler (1828)
Organic compounds were synthesized from inorganic sources!!
O

NH4NCO H2N NH2

ammonium Urea
cyanate

How many organic compounds are there?

“…..in 2001 there were about 16 million organic compounds
known!!”

How many more are possible?

There is no limit
 ***Life Is Organic Chemistry****
Organic Chemistry is the Chemistry
of the Compounds of Carbon

origin of life
CH4, CO2, H2O, NH3, H2
electric discharges
(like lightning)

highly reactive species

amino acids, HCHO, HCN, purines, pyrimidines

 Colors: Organic Chemistry

O
OH
…protein chain
uncoils, liberating
HO astaxanthin…
ASTAXANTHIN
O
 Nature Plays Holi………..

Cornflower Poppy
 An organic molecule’s contribution
to freedom struggle!!
O
H
With expansion of British power in Bengal, N
indigo planting became more and more
commercially profitable due to the demand for
Blue Dye in Europe. N
H O
The indigo planters mercilessly pursued the
peasants to plant indigo instead of food crops.
They provided loans at a very
high interest. Once a farmer took such loans he
remained in debt for whole of his life before passing
it to his successors. The farmers could make no profit
by growing indigo.

The Indigo revolt (Nil bidrōhō) was a peasant

movement and subsequent uprising of indigo farmers
against the indigo planters that arose in Bengal in 1859.
Vietnam's war against
Agent Orange
The Vietnam War ended in 1975,
but the scourge of dioxin
contamination from a herbicide
Cl
known as Agent Orange did not.
OR
O
Between 1962 and 1970, millions of gallons Cl O
of Agent Orange were sprayed across parts 2,4-dichlorophenoxyacetic acid
of Vietnam. An estimated 19 million gallons O
of Agent Orange were used in South Vietnam Cl O
OR
during the war. Operation Ranch Hand
Cl Cl
2,4,5-trichlorophenoxyacetic acid

According to Vietnam's Red Cross, Cl O Cl

150,000 children have Cl O Cl

problems resulting from Agent Dioxin
Orange (50/50 mix of two herbicides) (by product of Agent Orange)
 Topics

 Stereochemistry
 Conformational Analysis
 Nucleophilic Substitution at a Saturated
Carbon and Eliminations reactions
 Recommended Books

1. Organic Chemistry by Clayden, Greeves, Warren and

Wothers
2. Organic Chemistry by P. Y. Bruice

3. A Guide Book to mechanism in Organic Chemistry

by P. Sykes
 Stereochemistry

•Isomers that have same formula and connectivity but differ

in the position of the atoms in space
•Chemistry that studies the properties of stereoisomers

Static Stereochemistry Stereochemistry of Molecules

Number of isomers, structure, energy,

physical and chemical properties

Dynamic Stereochemistry Stereochemistry of Reactions

Stereochemical requirements and outcome of chemical reactions

 How do you identify isomers
Yes Do the compounds have the No
Isomers Not Isomers
Same molecular formulae?

Yes Do the compounds have the Constitutional

Stereoisomers No
Same Connectivity? O
OH

Can the compounds be interconverted by rotation about single bonds

H3C H Yes
H No
H
H CH3 Conformational Configurational
H H
H H

H3C CH3 Optical Is the isomerism at a double bond? Geometric

No Yes

Are the compounds have non-superimposable mirror images?

Yes No
Cl H
H3C H H3C Cl
Enantiomers Diastereomer
Cl Cl H3C H H3C H
Br Br

H3CH2C H H
CH3 H3C CH2CH3
 Chiral An object that has a non-superimposable mirror image is said to be
"chiral" (Greek = cheir (handedness)) and one that has a superimposable
mirror image is "achiral".

CHIRALITY is a property of an object which is non-

superimposable with its mirror image. Most objects in the
environment are chiral. In chemistry this term applies to molecules,
specific conformations of molecules, as well as to macroscopic objects
such as crystals.

Chirality is removed if an object /molecule acquires a plane of

symmetry, or a center of symmetry.
• Many molecules and objects are achiral:
– identical to its mirror image
– not chiral

H H H H

Cl Cl Cl Cl
 Enantiomers A pair of molecules that are non-superimposable mirror images of each
other.
The most common type of "chirality" is observed when a carbon atom has four different
groups attached to it (so it must be sp3 hybridized). This carbon atom is then described as
a chirality center.

Other terms are chiral, asymmetric or stereogenic center (stereocenter).

Cl Cl

H3CH2C H H CH2CH3
CH3 H 3C

Cl=D?
Small differences also matter
 Enantiomers and Chirality
O -
CN HO CN
R R
H H

How many products are formed ?

O
HO CN
O
NC OH R R
R R H H
H H B
A
CN
CN Approach from back face of the carbonyl
Approach from front face of the carbonyl
What is the relation between A & B?
HO
NC OH CN

A&B are non superimposable mirror images R R

H H

A B
A&B are chiral and Enontiomers (Mirror images)
 Elements of symmetry

O HO
HCN HO CN CN
Plane of symmetry through
Me Central C-atom, OH & CN
H3C CH3 Me Me Me

Acetone Cyanohydrine

Cl H
Cl H
F H Center of symmetry
F H
Or inversion center
H F H F

H Cl H Cl

Any structure that has no plane of symmetry or inversion center can exist as
two non super-imposable mirror-images (enantiomers)
 Stereogenic centres
If a molecule contains one carbon atom carrying four different groups, generally do not possess
a plane of symmetry or inversion center and must therefore be chiral.

A carbon atom carrying four different groups is a stereogenic or chiral centre

Constitutional and Stereo Isomers

OH R *
OH HO CN HO CN
R * R R
CN CN
H H
Enontiomers
Constitutional Isomers
Going from one enontiomer to the
other requires bond breaking
NC
R HO CN NC H H OH
R R
CN R R
H OH CN

Trans-cis isomers Three conformations of same enontiomer:

Going from one to the other requires
-bond should be broken rotation about C-C bond
Stereo isomers
Chirality Centers?
 Racemic mixture

A racemic mixture is a mixture of two enantiomers

in equal proportion

MeMgCl
:
CHO H OH
OH HO H
50 : 50

OH HO H HO H
CHO

O :
O O
OH

50 : 50
 Cahn-Ingold-Prelog rules : CH3 CH3

HO H H OH

CH2 CH2
Absolute configuration : CH3 CH3

The R & S notation Both are "2-butanol''

1. Assign priority sequence to the four groups attached to a stereogenic

carbon following sequence rule
2. Observe the stereogenic centre from a direction opposite to the group
of lowest priority
3. Trace the path from 1 to 2 to 3.
If clockwise R (rectus, right)
If anti clockwise S (sinister, left)
 Sequence rules:
1. Priority is first assigned on the basis of the atomic number of the atom
that is directly attached to the stereo centre. CH 3 ?
(1) H O H (4)

CH2 ?
CH3
2. When a priority cannot be assigned on the basis of AN, then the
next set of atoms/groups are examined. (3) CH3 H, H, H
(1) HO H (4)

CH2 H, H
(2)
CH3 C
3. Rotate the structure so that (4) is directed away from us.
3
CH3 CH3
4 OH 1
HO H H
CH2
CH2CH3
R
CH3 2
4. Groups containing double or triple bonds are assigned as if both
atoms were duplicated and triplicated.

C Y C Y

(Y) (C)

(Y) (C)

C Y C Y

(Y) (C)

CH CH2 CH2CH3

Vinyl or ethyl which one gets higher priority?

H H
H H
C C H
C C H
H H
(C) (C)
H, C, C H, H, C

Vinyl>Ethyl
 CO2H CO2H

C C
H H CH3
H3C NH2 H2N
Natural alanine Unnatural alanine
(S)-alanine (R)-alanine

H Br H
Cl
(2S, 3S)-2-bromo-3-chlorobutane
H3C CH3
 Chiroptical properties
Enantiomers: similar chemical and physical
properties (melting points, boiling points, heat of
combustion etc.),

Differences in direction of rotation of plane

polarised light and interactions with chiral
molecules (reagents, solvents, catalysts etc).

Diastereomers have different physical and chemical properties

•Any material which rotates the plane of the polarized light can be termed as
"optically active"
•Compounds featuring chiral centers are optically active
if they do not contain plane of symmetry or an inversion symmetry.

•Rotation of plane of polarized light

•towards left (levorotatory), it will be designated as l, or -
•towards right (dextrorotatory), will be designated as d, or +
•Enantiomers rotate plane of polarised light in opposite directions, but to the same extent
(clockwise = +ve, counterclockwise = -ve).
•An achiral molecule is optically inactive and cant show any rotation

CH2OH CH2OH

Me H H Me
Et Et
(R)-2-methyl-1-butanol (S)-2-methyl-1-butanol
+5.75 specific rotation []D20°-5.75

The specific rotation is the number of degrees of rotation caused by a solution of

1.0 g of the compound per mL of solution in a sample tube 1.0 dm long at a specified
temperature and wavelength. T 
[] =
lxc
 T 
[] =
lxc

[] = specific rotation;  = observed rotation;

T = temperature in C; l = length of the sample tube in decimeters;
 = wavelength of the incident light c = is the concentration of the sample in
(when the sodium D-line is used,  is indicated as D) grams per milliliter of solution
A 50:50 mixture of a pair of enantiomers is called a racemic mixture. This is optically inactive
since the rotations produced by each of the enantiomers must cancel each other out.

If there is more of one enantiomer than the other, then the optical purity of a sample can be
determined by measuring the rotation and comparing it to that of a pure enantiomer. This
can be used to establish the enantiomeric excess (ee) of the mixture.

observed specific rotation (obs)X 100

optical purity =
(enantiomeric excess; ee) specific rotation of the pure enantiomer (max)

= % of R - % of S
65 of % of R and 35 % of S
ee of the compound is 30%

Louis Pasteur
 D and L-systems (relative configuration)
The D/L systems relies on the chemical correlation of the configuration of the
chiral center to D-glyceraldehyde.
The accepted convention for drawing D(+)-glyceraldehyde places the hydrogen atom
at the left and the hydroxyl at the right, with the aldehyde at the top.
CHO CHO

H OH HO H

CH2OH CH2OH
D(+)-glyceraldehyde L(-)-glyceraldehyde

IMPORTANT NOTE:
Although D-glyceraldehyde is dextrorotatory (rotates the plane of polarized
light to the right), the compounds correlated to D-glyceraldehyde do not have
to be dextrorotatory, i.e. could rotate light to the left.
Therefore, D-prefix is not correlated with the (+) or (-) specific rotation,
and the D-compound can be l, (or -), and vice versa L-compound can be d
(or +).
D/L-system is almost abandoned in favor of the Cahn-Ingold-Prelog (CIP)
nomenclature, exception with carbohydrates and aminoacids, where the DL-
nomenclature has been traditionally used.
 GRAPHICAL REPRESENTATION OF NONPLANAR MOLECULES

Representation of the 3D-structures of molecules as their 2D-projections:

1. Fisher projection
Perspective formula
2. Wedge projection
COOH HOOC HOOC
Fisher projection:
The tetrahedral atom is viewed H3C NH2
H3C NH2 H2N CH3
perpendicularly to an edge formed
by connecting two of its ligands. H H
The convention is that the two
H 2
vertical bonds in the projection are 2
pointing behind the plane of COOH COOH
projection (plane of paper sheet), 3 1 1 3
and the two horizontal bonds are H3C NH2 H2N CH3
pointing towards the viewer.

90° rotation = one exchange = opposite configuration H H

180° rotation = two exchanges = same configuration S R
One Two
180° 90° exchange exchanges

H CH3
NH2
CH3

H2N CH3 H COOH H3C COOH H2N COOH

COOH NH2 H H

S R R S
Wedge projection:
It is obtained by viewing the tetrahedral center perpendicularly to the plane formed by three
atoms. The remaining atoms are oriented behind the plane of projection (dashed bond) and
towards the viewer (boldface bond).

F
H
D H
90° rotation along green axis

Cl F
D Cl
rotation along red axis

Cl F Note that, in contrast to Fisher

projection, the rotation of the wedge
projection about axes perpendicular
H D or coplanar with the plane of
projection does not change anything.

This projection is therefore by far less ambiguous than Fisher projection.

 In the case of large linear molecule the molecule backbone has to be laid on the
plane of the paper such that the substituents pointed towards and/or away from
the viewer

HOCH2CH(OH)CH(OH)CH(OH)CHO RRR RRS RSR RSS

SSS SSR SRS SRR
Ribose, carbohydrate
C5(H2O)5
OH OH
OH
CHO RRR CHO
HO CHO SSS HO
HO OH
OH OH OH OH
OH OH CHO
HO
OH OH OH
OH OH
CHO CHO CHO
HO OH
HO HO
OH OH CHO
OH OH HO OH OH

RSR OH OH
RRS RSS
SRS
SSR SRR
 CHO
H OH

HO H
H OH
H OH
CH2OH
(+) D-Glucose

(2R,3S,4R,5R)-2,3,4,5,6-Pentahydroxyhexanal
 Sawhorse projection

The C-C bond is viewed at an angle.

View

This projection is difficult to use with acyclic molecules but is most popular for
representation of cyclic molecules e.g. saturated six-membered rings.
 Newman projection:

The molecule with two tetrahedral centers is viewed along the C-C axis.
The atom in front is represented as a three-way branch, the atom in the back as
a circle with three outgoing bonds.

DH2C-CH2D

This projection is most useful to understand steric relations between ligands

linked to adjacent tetrahedral centers and is most popular
 Interconversions of representations

b c y
a b c
b c a b c
a
x z x z y
y y x z x
z
a
Fisher projection Sawhorse projection Newman projection
a b c b c y
b c b c
a a
z x
z x y
y x z
y x z a
 Z/E Geometry of Double Bonds

CIP rules used to geometrical isomers of olefinic compounds

Precedence of ligands at both X & Y of the double bonds is determined pairwise.
If both higher precedence ligands are
on the same side of the double bond the configuration is Z,
if on the opposite sides the configuration is E.

Z (zusammen, together) E (entgegen, opposite)

H H Br 1 F

1 1
H3C CH3 1
H Cl
(Z)-2-butene
Or cis-2-butene (E)-2-bromo-1-chloro-1-fluoroethene
 H CH3
Br CH2CH3
H3C

CH3
Cl H
H CH3

(Z)-1-bromo-1-chloro-1-butene (Z,4S)-3,4-dimethyl-2-hexene

H3CH2C CH2CH2CH3

H3C CH2CH2CH2CH3

(E)-3-methyl-4-propyl-3-octene
(2E),(4E)-2-chloro-2,4-hexadiene
 Nitrogen chirality center

The inversion barrier is only 6 kcal/mol for R= alkyl

Ammonia: inverts 2X1011 times for second
Inversion is very fast and difficult to separate
 Inversion becomes slow when
•N is in three-membered ring

 N cannot achieve a 1200 bond

angle in a 3-membered ring
 The two enantiomers can be
separated

•N-atom is connected to atom which has unshared lone pair of electrons

CH3
Cl Me Me Cl N

N
N N
H3C

Me Me Tröger’s base

Two enantiomers have been separated Nitrogen at bridgehead position,

Pyramidal inversion prevented, chiral
Phosphorus chirality center

P
C(CH3)3
CH3 CH3
P C(CH3)3

inversion barrier 32.7 kcal/mol

P
H3C
H2C=HCH2C

[]D = 16.80
S-enantiomer
 Nitrogen, Phosphorus, Sulfur attached to four different groups

CH3
CH3
Br
Br H N
N H
CH2CH2CH3
H3CH2CH2C CH2CH3 H3CH2C

a pair of enantiomers
O O

H P
P H
H 3 CH 2 CO OCH 2 CH 3
OCH 3 H 3 CO

16 O
a pair of enantiomers
O18

a pair of enantiomers
H3C
Diastereomers
•Diastereomers are stereoisomers that are not mirror images.
•Two diastereomers are different compounds and have different
relative stereochemistry.
Diastereomers may be chiral (have no plane of symmetry):
Ar CO2Me Ar CO2Me

O O

Diastereomers may be achiral

OH OH

plane of symmetry
Relative Configurations in Compounds with Multiple Chiral Centers.

•The use of CIP nomenclature requires assignment of R,S descriptors

for every center. The quicker way (older and a more ambiguous one) is
by using threo/erythro nomenclature.
•Threo/erythro It requires vertical projection of main chain.
•threo-compounds are defined as those that have two groups of higher
precedence on each carbon atom on the opposite sides of the chain.
•erythro on the same side.

CH3 CH3 CH3 CH3

* * H OH HO H H OH HO H
H3C CH CH CH3
H Cl Cl H Cl H H Cl
Cl OH
CH3 CH3 CH3 CH3
3-Chloro-2-butanol
A B C D
erythro enantiomers threo enantiomers

A&C
A&D
diastereomers
B&C
B&D
 Tartaric acid
HOOC-CH(OH)-CH(OH)-COOH 22 = 4 stereoisomers ?

OH OH

R HO2C R S
HO2C R
+12 CO2H CO2H
0
168-170 °C 146-148 °C
OH diastereomers OH
?
enantiomers
OH OH
-12 R
HO2C S S HO2C S
168-170 °C CO2H
CO2H

OH OH

HO2C CO2H
R S
COOH
COOH HO OH
HO H COOH
H OH
H OH
HO H H OH

COOH
H OH
COOH
COOH
pair of enantiomers
meso compound
 Compounds with no stereogenic centres
CH3

The presence of chiral atom is

neither a necessary nor a sufficient
H
COOH condition to be optically active
Br Substituted adamantane

H3C H
Me H H Me C C C
C
C
H H H
Me Me achiral
H

These mirror images are not superimposable - enantiomers

O O
H H
N N
PPh2
rotation around the single
bond is restricted PPh2
N N
H H
O O
nonsuperimposable enantiomers
AXIAL CHIRALITY: HOW to ASSIGN configurations
(R or S)?
 Ra or P (plus) and Sa or M (minus), subscript “a” refers to axial

• The CIP priority rules are used to assign priority to the end groups
• The near groups have a higher precedence over far groups
• The chiral axis is viewed end-on and the sense of configuration determined.

2 4
2 4 3 1
H H
3 H CH3
4 2 1
H3C H C C C H CH3
H3C 4 H2
CH3 1 3 3 CH
3
1
 1 1
NO2 NO2
4 3 3 4
HOOC NO2 O2N COOH

COOH COOH
2 2
Q. Identical, enantiomeric, or diastereomeric?
H3C
CH3
&
&

CH3
CH3 CHO CH2OH
H NH2 H OH
&
HO H H NH2
CH2OH CHO
& O
S S

COOH Br COOH H Cl
H H H CH3
H Br &
H Cl Ph & H Ph
Cl H Cl H
CH3 H
OH
OH