First Year Organic Chemistry

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

Teacher:
Dr. Samik Nanda

Organic Chemistry:
P. Y. Bruice

Organic Chemistry:
Clayden, Greeves,
Warren, Wothers

A Guide Book to mechanism

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

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 (except the number of atoms in the universe).
***Life Is Organic Chemistry****
Organic Chemistry is the Chemistry
of the Compounds of Carbon
why study organic
chemistry?

…protein chain
uncoils,
liberating
astaxanthin…
 Nature Plays
Holi………..

Cornflower
Poppy
 An organic molecule’s
contribution
to freedom struggle!!
With expansion of British power in Bengal,
indigo planting became more and more
commercially profitable due to the demand for
Blue Dye in Europe.

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
Vietnam's war against
Agent Orange
The Vietnam War ended in 1975,
but the scourge of dioxin
contamination from a herbicide
known as Agent Orange did not.
Between 1962 and 1970, millions of gallons
of Agent Orange were sprayed across parts
of Vietnam. An estimated 19 million gallons
of Agent Orange were used in South Vietnam
during the war. Operation Ranch Hand

According to Vietnam's Red Cross,

150,000 children have
problems resulting from Agent
Orange (50/50 mix of two herbicides)
 Topics

❖ Stereochemistry: 3L
❖Conformational Analysis: 3L
❖Nucleophilic substitution at saturated
carbon and related topics: 3L
❖Dynamic stereochemistry: 3L
❖Doubt clearing; Class test
 Drawing Molecules

X-ray picture of linoleic acid

Pictorial mimicry by drawing simple lines
 Stereochemistry

Static Stereo Chemistry Stereo chemistry of Molecules

Number of isomers, structure, energy,

physical and chemical properties

Dynamic Stereo Chemistry Stereochemistry of Reactions

Stereo chemical 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 No Constitutional

Stereoisomers
Same Connectivity?

Can the compounds be interconverted by rotation about single bonds

Yes No

Conformational Configurational

Optical Is the isomerism at a double bond? Yes Geometric

No

Are the compounds have non-superimposable mirror images?

Yes No

Enantiomers Diastereomer
 Chiral An object that has a non-superimposable mirror image is said to be
"chiral" (Greek = "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.
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 hybridised). This carbon atom
is then described as a chiral center or center of chirality.

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

Cl=D? Small differences also matters

 Enantiomers and Chirality

How many products are formed ?

A B

What is the relation between A & B?

A&B are non superimposable mirror images

A&B are chiral and Enontiomers

 What happens when cyanide is added to acetone

So, any structure that has no plane of symmetry can exist as two mirror-image forms
(enantiomers)
Some examples of ‘structures’ other than chemical structures which are chiral
 Amusing ?
The ancient Egyptians had less care for the chirality of hands……
 Elements of symmetry

HCN
Plane of symmetry (σ) through
Central C-atom, OH & CN

Center of symmetry (i) Or inversion center

Any structure that has no plane of symmetry or inversion center can exist as
two non super-imposable mirror-images (enantiomers)
Visual demonstration of chirality and superimposable nature of palm in a specific orientation

90 deg 180 deg 270 deg

Original

360 deg Mirror image Palm hold in this way are not
superposable with its mirror images
Hence chiral
Rotation and reflection operation; alternating axis of symmetry visualization
Most accurately, all molecules which have a n-fold alternating axis of
symmetry (equal to an improper rotation axis or a rotary-reflection axis,
symmetry element S ) are achiral (and thus superimposable with their mirror
n

images).
S1 = σ; S2 = i
Molecule with alternating axis of symmetry (S2) ; inversion center
Molecule with alternating axis of symmetry (S4)
S1 = σ; The
rotary reflection operation consists of rotating through
an angle 360°/n about the axis, followed by reflecting in a plane
perpendicular to the axis.
 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

*
*

Enontiomers
Constitutional Isomers
Going from one enontiomer to the
other requires bond breaking

Trans-cis isomers Three conformations of same enontiomer:

Going from one to the other requires
π-bond should be broken rotation about C-C bond
Stereo isomers
 Racemic mixture

A racemic mixture is a mixture of two enantiomers

in equal proportion
Chiral/achiral (close look)
 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
Fisher projection:
The tetrahedral atom is viewed H3C NH2
perpendicularly to an edge formed
by connecting two of its ligands.
The convention is that the two
H 2
vertical bonds in the projection are 2
pointing behind the plane of
projection (plane of paper sheet), 3 1 1 3
and the two horizontal bonds are
pointing towards the viewer.

90° rotation = one exchange = opposite configuration

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

S R R S
Projection of a tetrahedral molecule onto a planar surface.

Visualizing a Fischer 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
 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
 Stereochemistry
Stereogenic Centers
• Many
biologically
active
molecules
contain
stereogenic
centers on
ring carbons.
 Cahn-Ingold-Prelog rules :

Absolute configuration :
The R & S notation

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.

2. When a priority cannot be assigned on the basis of AN, then the

next set of atoms/groups are examined.

3. Rotate the structure so that (4) is directed away from us.

 Sequence rules
# Atoms directly attached to the stereogenic central atom must be
sequenced first

# If the priority still remains undecided, pass to the next atom in the
ligands…..

# Continue until a decision is reached…….

4. Groups containing double or triple bonds are assigned as if both
atoms were duplicated and triplicated.

Vinyl or ethyl which one gets higher priority?

Vinyl>Ethyl
Sequence rules
Expanding Out Multiple Bonds With “Phantom Atoms”
Sequence rules
 Sequence rules

Labeling Stereogenic Centers with R or S

• If two isotopes are bonded to the stereogenic center,

assign priorities in order of decreasing mass number.
Thus, in comparing the three isotopes of hydrogen, the
order of priorities is:
 Sequence rules
Labeling Stereogenic Centers with R or S
• To assign a priority to an atom that is part of a multiple bond,
treat a multiply bonded atom as an equivalent number of
singly bonded atoms. For example, the C of a C=O is
considered to be bonded to two O atoms.

• Other common multiple bonds are drawn below:

 Sequence rules

Labeling Stereogenic Centers with R or S

 Sequence rules

Whatever (“R” or “S”) comes remains as it is

 Sequence rules

Whatever (“R” or “S”) comes it is just opposite to that

Sequence rules

(S)-(4,4-dimethylpent-1-yn-3-yl)benzene

CIP rule: Ph>acetylene>tbu>H

Few extra on CIP rule
 Sequence rules

Extra branching at the small size ring will alter priority sequence
 Sequence rules

When all the atoms next to a stereogenic center is part of ring, stop at the more
branching point….irrespective of the size of the ring
 Sequence rules

In case a ligand bifurcates, one should proceed along the branch proving the highest
priority until a difference is encountered. The decision must be made at the earliest
opportunity and cannot be changed further along the chain………..
 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)

1

1 1
1

(Z)-2-butene
Or cis-2-butene (E)-2-bromo-1-chloro-1-fluoroethene
(Z)-1-bromo-1-chloro-1-butene (Z,4S)-3,4-dimethyl-2-hexene

(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 2 x 1011 times per second

Inversion is very fast and difficult to separate

Energy profile in pyramidal inversion
 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

Tröger’s base

Two enantiomers has been separated Nitrogen at bridgehead position,

Pyramidal inversion prevented, chiral
Configuration determination at nitrogen stereogenic center
 Phosphorus stereogenic center

Important Points To Remember

* In PH3 hybridization does not take place.
* The pure p orbitals take part in bonding.
* In phosphine, orthogonal 3p orbitals overlap
with 1s orbital of H.

Drago’s rule:
# Central atom belongs to third or higher period.
# Central atom has one lone pair.
[α]D = 16.80 # The electronegativity of the terminal atom is less
than carbon.
S-enantiomer
Pyramidal inversion is not possible for P, As and others
Nitrogen, Phosphorus, Sulfur attached to four different groups

a pair of enantiomers

16 18
a pair of enantiomers

a pair of enantiomers
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):

Diastereomers may be achiral

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.
 Tartaric acid (constitutionally symmetrical molecules)
HOOC-CH(OH)-CH(OH)-COOH

R R S
R

S S R
S

R S
 Constitutionally symmetrical chiral molecules [2(n-1)] stereoisomers { n is odd}

Constitutionally symmetrical chiral molecules [2(n-1) + 2(n-2)/2] stereoisomers { n is even}

C2 axis of symmetry and visual demonstration
 Stereochemistry
Disubstituted Cycloalkanes
• Consider 1,3-dibromocyclopentane. Since it has two
stereogenic centers, it has a maximum of four stereoisomers.

• Recall that a disubstituted cycloalkane can have two

substituents on the same side of the ring (cis isomer, A) or on
opposite sides of the ring (trans isomer, B). These
compounds are stereoisomers but not mirror images.
 Stereochemistry
Disubstituted Cycloalkanes
• To draw the other two stereoisomers if they exist, draw mirror
images of each compound and determine whether the
compound and its mirror image are superimposable.

• The cis isomer is superimposable on its mirror image, making

the images identical. Thus, A is an achiral meso compound.
 Stereochemistry
Disubstituted Cycloalkanes
• The trans isomer is not superimposable on its mirror image,
labeled C, making B and C different compounds. B and C are
enantiomers.

• Because one stereoisomer of 1,3-dibromocyclopentane is

superimposable on its mirror image, there are only three
stereoisomers, not four.