First Year Organic Chemistry

Monday 7-30 AM
Wednesday 10-30 AM

Spring Semester
12-13 Lectures

Venue V1
Teacher:
Professor J K RAY

Organic Chemistry (2nd Ed.):

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 Whler (1828)
Organic compounds were synthesized from inorganic sources!!
O

NH4NCO
ammonium
cyanate

H2N

NH2

Urea

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

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

highly reactive species

amino acids, HCHO, HCN, purines, pyrimidines

why study organic chemistry?

O
OH

HO
O

ASTAXANTHIN

protein chain
uncoils, liberating
astaxanthin

Nature Plays Holi..

Cornflower

Poppy
O

O H
HO

alkalined
O

O
sugar

sugar

HO

O
O

acidic
O
sugar

sugar

An organic molecules contribution

to freedom struggle!!
O
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 bidrh) was a peasant
movement and subsequent uprising of indigo farmers
against the indigo planters that arose in Bengal in 1859.

N
H

H
N

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

Cl
OR

O
Cl

2,4-dichlorophenoxyacetic acid
O
Cl

Cl

Cl

OR

2,4,5-trichlorophenoxyacetic acid

According to Vietnam's Red Cross,

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

Cl

Cl

Cl

Cl

Dioxin
(by product of Agent Orange)

Chlorophyll : The Photosynthetic

Pigment
Chlorophyll and several
other pigments such as
beta-carotene, organized
in clusters in the thylakoid
membrane are involved in
the light reaction. Each of
these differently-colored
pigments absorbs a
different color of light and
passes its energy to the
centralchlorophyll

Chemical reaction involved in

photosynthesis:
6 CO2(gas) + 12 H2O(liquid) + photons
C6H12O6(aqueous) + 6 O2(gas) + 6
H2O(liquid)
carbon dioxide + water + light energy
glucose + oxygen + water

Cocaine
From coca leaves was the first anaesthetic, and also blocks Na+ channels with
lower affinity and specificity than tetradotoxin.

Ellagic Acid Chemical Composition

How does ellagic acid work?

Ellagic acid acts as a scavenger to "bind"
cancer-causing chemicals, making them
inactive.

Ellagic acid is a powerful antioxidant, polyphenol found in red raspberries, Arctic

bramble, and cloudberries strawberries and walnuts.

Bacterial vs. Viral Infections

Why dont antibiotics work for viral infections?

MicrobeLibrary.org; Jean-Yves Sgro, University of Wisconsin

Polio Virus

http://www.microbelibrary.org/microbelibrary/files/ccImages/Articleimages/simonson/Images/Streptococcus%20sobrinus%20fig1.jpg

Streptococcus

Can you think of some illnesses caused by viruses or bacteria?

Bacterial Infections

Viral Infections

strep throat

the flu

gastroenteritis

colds

cholera

AIDS

tuberculosis

hepatitis

food poisoning

chicken pox

botulism

gastroenteritis

gangrene

measles

necrotizing fasciitis

mumps

boils, abscesses

E. Bola

pneumonia

pneumonia

acne

West Nile

meningitis

cervical cancer

ulcers

Treatment of bacteria diseases

PROBLEM
there are many chemicals that are lethal to bacteria (e.g.
cyanide), but cannot be used to cure because they are
lethal to the host as well
problem is to find substances that attack a metabolic pathway
found in bacterium but not in host

SOLUTION
Natural products
originally discovered as secretions of fungi or soil bacteria
Semi-synthetic products
natural products chemically modified in laboratory to improve
efficacy of natural product, reduce its side effects
Completely synthetic products

Antibiotics
first known use of antibiotics - ancient Chinese (2,500 years ago)
ancient Egyptians and Greeks used molds and plants to treat infections

Definition:
chemotherapeutic agent that inhibits or stop the growth of
micro-organisms (bacteria, fungi or protozoans)
small molecules with a molecular weight less than 2 kDa
first produced and isolated from living organisms:
- fungi Penicillium antibiotic penicillin
- bacteria Streptomyces antibiotic streptomycin
then obtained by chemical synthesis antibiotic sulfa drugs
Term "Antibiotic"
- first used for substances extracted from fungus or other microorganism
- now used also for synthetic and semi-synthetic drugs with antibacterial effects
Other informations animated:
http://www.hhmi.org/biointeractive/Antibiotics_Attack/frameset.html

Brief history of fight with bacteria disease

2000 B.C.
1000
1850
1920
1945
1955
1960-1999
2000

Are you sick? Take this root!

Treatment with root is profane. Pray!
Pray is superstition. Take this nostrum!
Nostrums are charlatanry. Take this pill!
Old pills are not efficient. Take penicilin!
Oh, bacteria mutated! Take tetracyclin!
Other 39 Oh Take more effective antibiotic!
Bacteria is winning! Take this root!

Types of antibiotics
1) Based on their origin
natural (from bacteria, fungi)
Streptomyces (antibiotics: streptomycin, neomycin, vancomycin
erythromycin, rifamycin, chloramphenicol, monensin)
Pseudomonas (fosfomycin)
Bacillus sp. (mersacidin, bacitracin, polymyxin)
Penicillium (penicilin, griseofulvin)
semi-synthetic
synthetic (sulfonamids, trimethoprim, chinolons)
2) Based on their chemical composition
Penicillin
Cephalosporins
Tetracyclines
Macrolides
others

Penicillin
discovered from the fungus Penicillium notatum in 1928 by
Alexander Fleming
Alexander Fleming
6.8.1881 (Scotland) 11.3.1955 (England)
Fields: bacteriology, immunology
Nobel Prize in Physiology or Medicine in 1945

Fleming receiving the Nobel prize from

King Gustav V of Sweden (right), 1945

Accidental discovery
On 3 September 1928, Fleming returned to his laboratory having spent August on
vacation with his family. Before leaving he had put his cultures of staphylococci in a
corner of his laboratory. On returning, Fleming noticed that one culture was
contaminated with a fungus, and that the colonies of staphylococci that had
immediately surrounded it had been destroyed, whereas other colonies further away
were normal. Fleming identified the mould that had contaminated his culture plates as
being from the Penicillium genus, and named the substance it released penicillin on 7
March 1929.

Antibiotic resistance
Definition: ability of microorganism to resist the antibiotic effects
antibiotic resistance evolved via natural selection through
random mutation, or by applying stress on a population
once such a gene is generated, bacteria can transfer genetic
information by horizontal transfer (between individuals) of
plasmid by bacterial conjugation
if bacterium carries several resistance genes = multiresistant
Antibiotic

Discovered

Introduction
Resistance
into clinical use first identified

Penicillin

1928

1943

1946

Streptomycin

1943

1947

1959

Tetracycline

1948

1952

1953

Vancomycin

1956

1972

1988

Dangers of antibiotics
1) allergic reactions - most often with penicillin
2) destruction of helpful microbes
3) damage to organs and tissues

Reasons of widespread resistance:

overuse of broad-spectrum antibiotic
incorrect diagnosis
unnecessary prescriptions
improper use of antibiotics by patients
use of antibiotics as livestock food additives for better growth

What can you do to delay the spread of antibiotic resistance?

don't ask your doctor for antibiotic to treat viral disease for
which antibiotics are useless !!!
- however, doctor can prescribe antibiotic if you are infected by influenza
virus,not to fight the virus but to protect you against a secondary bacterial
infection of your damaged lungs

use all doses prescribed even you are feeling better

- this will minimize the opportunity to select for resistance among the
bacteria that remain late in the infection

don't save unused antibiotics for later self-medication

dont take antibiotics to prevent illness
- this only increases your risk for developing resistant infections

Farmers can help by avoiding the use of

antibiotics (similar to those used in humans)
in their livestock

Resistance to Penicillin and its derivatives

is caused by a specific enzyme

Penicillins: Mechanism of
Action
Penicillins inhibit the bacterial transpeptidase enzyme by
mimicking its natural substrate, the terminal D-alaD-ala
Transpeptidase attacks the -lactam ring of penicillin, forms a
covalent bond; enzyme is now out of business

Topics
Stereochemistry
Nucleophilic substitution at
saturated carbon and Elimination
reaction
Conformational Analysis
Pericyclic Reactions

Drawing Molecules
H

HH

HH

HH

HH

H3C

OH

HH

or

H H

HH
H H
linoleic acid

CH3CH2CH2CH2CH2CH=CHCH2CH=CHCH2CH2CH2CH2CH2CH2CH2CO2H

linoleic acid

or
H

HH

HH

H H

C C

H H H H
linoleic acid

H H

H
C

X-ray picture of linoleic acid

OH

linoleic acid

CO2H

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

Isomers

Stereoisomers

Yes

Yes

Do the compounds have the

Same molecular formulae?

Do the compounds have the

Same Connectivity?

No

Not Isomers

Constitutional

No

O
OH

H3C

H
H

H
H

CH3

H
H

H
H

H3C

CH3

Can the compounds be interconverted by rotation about single bonds

Yes
No
Conformational

Configurational

Optical

No

Is the isomerism at a double bond?

Are the compounds have non-superimposable mirror images?

Yes
No
Enantiomers
Cl

H3CH2C

Diastereomer
Cl

H
CH3

H
H3C

H3C
H3C

CH2CH3

Yes

Cl

Br

H
H

Geometric

H3C
H3C

Br

Cl
H

Stereochemistry
Stereochemistry:
The study of the three-dimensional structure of
molecules

Structural (constitutional) isomers:

same molecular formula but different bonding sequence

Stereoisomers:
same molecular formula, same bonding sequence,
different spatial orientation

Types of Stereoisomers
Two types of stereoisomers:
enantiomers
two compounds that are nonsuperimposable mirror
images of each other

diastereomers
Two stereoisomers that are not mirror images of
each other
Geometric isomers (cis-trans isomers) are one
type of diastereomer.

Stereochemistry
CH
3

Stereochemistry plays an important role in

determining the properties and
H reactions
of organic compounds: H3C CH2
CH3

H3C

H
CH2

Caraway seed

CH3

H
H2C
spearmint

CH3

Stereochemistry
The properties of many drugs depends on
HN
HN
their stereochemistry:
O
O
CH
CH3
NH3NH

O
NHCH3

Cl

Cl

Cl

O
CH3NH

Cl

(S)-ketamine

(R)-ketamine

anesthetic

hallucinogen

Stereochemistry
Chiral and Achiral Molecules:
Some molecules are like hands. Left and right hands are mirror images, but they
are not identical, or superimposable.

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 nonsuperimposable 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.

Achiral
Many molecules and objects are achiral:
identical to its mirror image
not chiral
H

Cl Cl

Cl Cl

Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane is a meso
compound:
an achiral compound that contains chiral
centers
often contains an internal mirror plane of
symmetry

Internal Plane of Symmetry

Cis-1,2-dichlorocyclopentane contains two
asymmetric carbons but is achiral.
contains an internal mirror plane of symmetry

Any molecule that has an Cl

internal
Cl mirror plane of
symmetry is achiral even if it contains asymmetric
carbon atoms.

Stereochemistry
Identifying of Stereogenic Centers:
Stereogenic centers may also occur at carbon atoms that are part of a ring.
To find stereogenic centers on ring carbons, always draw the rings as flat
polygons, and look for tetrahedral carbons that are bonded to four different
groups.

Contains a plane of symmetry

43

Stereochemistry
Drawing Stereogenic Centers - the wedge diagram:
In 3-methylcyclohexene, the CH3 and H substituents that are above and below the
plane of the ring are drawn with wedges and dashes as usual.

44

Internal Plane of Symmetry

Example: Which of the following compounds
contain an internal mirror plane of symmetry?
HO2C
HO
H

HO2C
HO
H

CO2H
OH
H

H Br

CH2CH3
C

H3CH2C

CO2H
H
OH

HO

H
Br

O
C OHF
C H

CH3
H

H 3C

H
C
F

Cl

H
Chiral vs.BrAchiral
CH3following molecules as chiral
Example: Identify the
or achiral.
CH3 C CH2CH3
Cl
CH3CHCH2CH2CH3

CH3

Br

Br

Br

Cl

CH3

CH3CCH2CH3
Cl

Br
H

trans-1,3-dibromocyclohexane
ethylcyclohexane

CH2CH3

CH3CH2

Br
H

H
Br

H
C

Br

CH2CH3

Asymmetric Carbons
Example: Identify all asymmetric carbons
present in the following compounds.
H

Br

OH H

H
H3C

CH3

CH2CH3
H
H

Br

Br
Br

H CH
3

Projection of a tetrahedral molecule onto a planar surface.

Visualizing a Fischer projection.

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

Cl
H3CH2C

H
CH3

Cl=D?

H
H3C

CH2CH3

Small differences also matters

Enantiomers and Chirality

O
R

CN

HO

CN

How many products are formed ?

NC

HO

OH
R

R
H

R
H

A
CN

Approach from front face of the carbonyl

CN
H

B
CN

Approach from back face of the carbonyl

What is the relation between A & B?

NC

A&B are non superimposable mirror images

A&B are chiral and Enontiomers

OH

HO

CN

R
H
A

H
B

(Mirror images)

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

R *

HO

OH

CN

CN

CN
H

HO
R

CN
H

Enontiomers

Constitutional Isomers

Going from one enontiomer to the

other requires bond breaking

NC
R
CN

Trans-cis isomers
-bond should be broken
Stereo isomers

HO
R

CN
H

NC
R

H
OH

H
R

OH
CN

Three conformations of same enontiomer:

Going from one to the other requires
rotation about C-C bond

Racemic mixture
A racemic mixture is a mixture of two enantiomers
in equal proportion

MeMgCl

CHO

:
OH

50

OH

HO

50

HO

CHO
OH

OH

HO

50

H
O
50

Cahn-Ingold-Prelog rules :
HO

Absolute configuration :
The R & S notation

CH3

CH3
H

OH

CH2

CH2

CH3

CH3

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
CH3 ?
that is directly attached to the stereo centre.
(1) HO

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

(1) HO
(2)

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

CH3
HO

CH3
H

CH2
CH3

OH 1
CH2CH3
2

H, H, H
H (4)

CH2

H, H

CH3

4. Groups containing double or triple bonds are assigned as if both

atoms were duplicated and triplicated.
C

(Y) (C)
(Y) (C)
C

(Y) (C)

CH2CH3

CH CH2

Vinyl or ethyl which one gets higher priority?

H

(C) (C)

H, H, C

H, C, C

Vinyl>Ethyl

(R) and (S) Nomenclature

In case of ties, use the next atoms along
the chain as tiebreakers.
2

CH2CH2Br
C

CH3CH2

H4
CH(CH3)2
1

CH(CH3)2 > CH2CH2Br > CH3CH2

C Y C
(R) and (S) Nomenclature
C

Treat doubleYand triple bonds as if both

C Y
C Y
O atoms in the
Y C
Cbond
were duplicated or
H
C triplicated:
Y C
Y

C
H

OH
C Y
CH2OH

C
Y

O 2 H
Y C

1
C C OH
4 H CH2OH
3

Y
C

C O
Y
C Y2
O C H

Y
C4 H
C

OH
CH2OH
Y

C
Y

Y
C

C
Y

C
Y

Determination of absolute configuration from Fischer presentation

Cl

Cl
Et

nPr
H

(R)-3-chlorohexane

nPr

Et
H

(S)-3-chlorrohexane

* lowest priority group is in vertical

* lowest priority group is not vertical

Me

Me
H

OH

HO

Et

Et

(S)

(R)

Very true if LP is on vertical bond

Horribly wrong if LP is on horizontal bond

Stereochemistry
Labeling Stereogenic Centers with R or S:
Since enantiomers are two different compounds, they need to be distinguished by
name. This is done by adding the prefix R or S to the IUPAC name of the
enantiomer.
Naming enantiomers with the prefixes R or S is called the Cahn-Ingold-Prelog
system.
To designate enantiomers as R or S, priorities must be assigned to each group
bonded to the stereogenic center, in order of decreasing atomic number. The
atom of highest atomic number gets the highest priority (1).

60

(R) and (S) Nomenclature

The two enantiomers of alanine are:

H3C

CO2H

CO2H

H
NH2

Natural alanine
(S)-alanine

H
H2N

CH3

Unnatural alanine
(R)-alanine

Stereochemistry
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:

62

Stereochemistry
Labeling Stereogenic Centers with R or S:

63

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

Ribose, carbohydrate
C5(H2O)5

OH

OH

OH

HO

CHO

HO
OH

OH

OH

HO
OH

OH

OH

OH

OH

OH

OH

OH

CHO
HO
OH

CHO

OH

CHO
HO
OH

OH
CHO
HO

OH

HO

RSR RSS
SRS SRR

SSS

OH
CHO

RRS
SSR

CHO
HO
OH

OH

CHO
OH

OH

Stereochemistry
Stereogenic Centers
Many
biologically
active
molecules
contain
stereogenic
centers on
ring carbons.

Stereochemistry
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:

Stereochemistry
Labeling Stereogenic Centers with R or S

(R) and (S) Nomenclature

Cl
3

H3 C
H

OCH2CH3

CH3

C H4
F 2NH2

Example priorities:
I > Br > Cl > S > F > O > N > 13C > 12C > 3H > 2H > 1H

Assign a configuration, R or S to each of these compounds

Br

Cl

HO

OH

Br

Cl

OH
NH2
HS

R = Me; CF3

CO2H

CHO

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)
H

1
H3C

Br 1

1
Cl

CH3

(Z)-2-butene
Or cis-2-butene

E (entgegen, opposite)

(E)-2-bromo-1-chloro-1-fluoroethene

Br

CH2CH3

CH3

H3C
CH3

Cl

(Z)-1-bromo-1-chloro-1-butene

Et

H3C

CH3

(Z,4S)-3,4-dimethyl-2-hexene

CH2CH2CH3

CH2CH2CH2CH3

(E)-3-methyl-4-propyl-3-octene

(2E),(4E)-2-chloro-2,4-hexadiene

I. Stereoisomers
H3C OH

Projections: 3D

H
H3C

Newman

CH3

H
Fischer

Br

HO
Br

H
H

HO

Br
CH3

CH3
CH3
(2R,3R)-3-bromo-2-butanol

72

I. Stereoisomers
H3C OH

Projections: 3D

H
H3C

Newman

CH3

H
Fischer

Br

HO
Br

H
H

HO

Br
CH3

CH3
CH3
(2R,3R)-3-bromo-2-butanol

Nitrogen chirality center

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

Ammonia: inverts 2X1011 times per 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

Me

N
H3C

Me

Two enantiomers has been separated

Trgers base
Nitrogen at bridgehead position,
Pyramidal inversion prevented, chiral

Phosphorus chirality center

C(CH3)3
CH3
P

inversion barrier 32.7 kcal/mol

H3 C

H2C=HCH2C

[]D = 16.80
S-enantiomer

CH3
C(CH3)3

Nitrogen, Phosphorus, Sulfur attached to four different groups

CH3

CH3
Br

H3CH2CH2C

CH2CH3

H3CH2C

Br
CH2CH2CH3

a pair of enantiomers
O

O
P
H3CH2CO

16 O

O18

H
OCH3

H
H3CH2CO

P
OCH2CH3

a pair of enantiomers

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

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

H3C

*
CH

*
CH

Cl

OH

3-Chloro-2-butanol

CH3

OH

HO

Cl

Cl

CH3

OH

HO

Cl

CH3

B
erythro enantiomers

CH3

CH3

H
Cl

CH3

CH3

threo enantiomers

diastereomers

A&C
A&D
B&C
B&D

Tartaric acid
stereoisomers ?

22 = 4

HOOC-CH(OH)-CH(OH)-COOH

OH

OH
HO2C

HO2C

OH

diastereomers

enantiomers
HO2C

S
CO2H

R
COOH

HO

HO

COOH

CO2H

CO2H

HO2C

OH

OH

OH

OH

OH

COOH

CO2H

CO2H

OH

HO2C

H
OH
COOH

pair of enantiomers

HO

OH

COOH
H

OH

OH
COOH

meso compound

The Chirality Axis

The Chirality Axis

Some molecules are chiral but do not contain a
chirality center. Some of these contain a chirality
axis, an axis about which groups are arranged so that
the spatial arrangement is not superimposable on its
mirror image.
Examples include substituted biphenyls and allenes:

Compounds with no stereogenic centres

The presence of chiral atom is neither a
necessary nor a sufficient condition to be
optically active

H3C

Me

C
H

Me
C

Me

Me

achiral

These mirror images are not superimposable - enantiomers

O

O
H
N

rotation around the single

bond is restricted

H
N

PPh2
PPh2

N
H

N
H
O

nonsuperimposable enantiomers

Chiral Compounds w/o Asymmetric Atoms

Allenes:
compounds containing a C=C=C unit
central carbon is sp hybridized
linear

substitutedallenes

In the appropriately substituted biphenyls,

rotation around the bond joining the rings is
restricted and the enantiomers can be isolated:

Conformational isomers that are stable, isolable compounds are called

atropisomers.

biphenyls

hasbeenresolved
halflifeforracemization
is78minat118oC

Substituted 1,1-binaphthyl derivatives exhibit atropisomerism due to

hindered rotation about the single bond that connects the two
naphthalene rings.
An example is (S)-(-)-BINAP shown below

Chiral Compounds w/o

Asymmetric Atoms

Conformational enantiomers:

compounds that are so bulky or so highly

strained that they cannot easily confert from
one chiral conformation to the mirror-image
conformation
locked into one conformation

Helical and propellor Molecules

Hexahelicene

Left handed and Right Handed

Cl

Cl
Cl
Cl

Propellor

Cl

Cl

Cl

Cl
Cl

Rotation restricted

Cl
Cl Cl
Cl

Cl

Cl

perchlorotriphenylamine

Optical Activity
Polarimetry is a laboratory technique that
measures the interaction between a
compound and plane polarized light.
Since enantiomers interact with plane
polarized light differently, polarimetry can
be used to distinquish between
enantiomers.

Optical Activity
Regular (unpolarized) light vibrates in all
directions.
Plane-polarized light:
light composed of waves that vibrate in only a
single plane
obtained by passing unpolarized light through
a polarizing filter

Optical Activity
When plane polarized light passes
through a solution containing a single
chiral compound, the chiral compound
causes the plane of vibration to rotate.
Polarimeter

Optical Activity
Chiral compounds are optically active:
capable of rotating the plane of polarized light

Enantiomers rotate the plane of polarized

light by exactly the same amount but in
opposite directions.
CH
CH3

H
CH2CH3
HO
(S)-2-butanol
+13.5o rotation

C
CH3CH2

H
OH

(R)-2-butanol
CH3
o
-13.5 rotation

Optical Activity
Compounds that rotate the plane of polarized light
to the right (clockwise) are called dextrorotatory.
d
(+)

IUPAC convention

Compounds that rotate the plane of polarized light

to the left (counterclockwise) are called
levorotatory.
l
(-)

IUPAC convention

Optical Activity

(observed )
[ ]
c l
where a = specific rotation
c = concentration in g/mL
l = path length in dm
a (observed) = rotation
observed for a specific
sample

Optical Activity
Example: A solution of 2.0 g of (+)-glyceraldehyde
in 10.0 mL of water was placed in a 100. mm
polarimeter tube. Using the sodium D line, a
rotation of 1.74o was observed at 25oC. Calculate
the specific rotation of (+)-glyceraldehyde.

(observed )
[ ]
c l

Optical Activity
Given: (obs) = 1.74o

1m
10 dm
l 100. mm

1.00 dm
1000 mm 1 m
2.0 g
c
0.20 g mL
10.0 ml

Find: []

1.74
o
[ ]
8.7
0.20 1.00

Optical Activity
H
HO

CH3

CH3

CH2CH3

CH3CH2

H
OH

+13.5o rotation

-13.5o rotation

(S)-(+)-2-butanol

CH3
(R)-(-)-2-butanol

A mixture containing equal amounts ofC(+)-2H

CH2CH3
butanol and (-)-2-butanol gives an observed
HO
rotation of zero degrees
Just like an achiral molecule

Biological importance of chirality

Chirality is a phenomenon that pervades the universe
Human body is structurally chiral
Helical seashells are chiral
Most plants show chirality in the way they wind around
supporting structures
Most of the molecules that make up plants and animals
are chiral and usually one form of the chiral molecule
occurs in a given species
All but one of the 20 amino acids are chiral and L-form
Almost all natural sugars are chiral
DNA itself has a helical structure and all naturally occurring
DNA turns to right.
Chiral molecules can show different handedness in
many ways, including the way they affect human beings

Chemical Properties of Enantiomers

Why the smells of Orange and lemons are different?

R- (+)-limonene
smell of orange

S- (-)-limonene
smell of lemons

Enantiomeric smell !!!

Perfumery compounds from jasmine

O

Jasmone

Cis-jasmone is the main compound in jasmone perfume

S
R

CO2Me

strong odour
(+)-Z-methyl epijasmonate

CO2Me

odourless
(-)-Z-methyl epijasmonate

Me
*
COOH

Ibuprofen
500 mg of one tablet contains only half of its as active drug

Me

Me

COOH

S is active

COOH

R is inactive

Stereochemistry
Physical Properties of Stereoisomers
Enantiomeric excess (optical purity) is a measurement of
how much one enantiomer is present in excess of the
racemic mixture. It is denoted by the symbol ee.
ee = % of one enantiomer - % of the other enantiomer.
Consider the following exampleIf a mixture contains
75% of one enantiomer and 25% of the other, the
enantiomeric excess is 75% - 25% = 50%. Thus, there is a
50% excess of one enantiomer over the racemic mixture.
The enantiomeric excess can also be calculated if the
specific rotation [] of a mixture and the specific rotation
[] of a pure enantiomer are known.
ee = ([] mixture/[] pure enantiomer) x 100.

Enantiomeric Excess
When a mixture of enantiomers is neither
enantiomerically pure (all one enantiomer) nor
racemic (equal amounts of two enantiomers), the
relative amounts of the enantiomers in the mixture
can be expressed as the enantiomeric excess (optical
purity).

e.e. = d - l x 100
d + l
(excess of one over the other) x100
=
(entire mixture)

Resolution of Enantiomers
Enantiomers have the same physical properties so they can not be separated directly.
A possible technique for separation is chemical modification into diastereomers, which
possess different physical properties. Once in hand, diastereomers can be separated
by physical means, such as boiling point or recrystallization and then converted back
into enantiomers.
Two key requirements:
1. The reaction must be reversible so that the enantiomers can be released.
2. The reagent that reacts with the enantiomers must be stereochemically pure.
Example: The resolution of (S) and (R)-2-butanol via esterification with
enantiomerically pure (R,R)-tartaric acid.
Key reaction: Esterification
O
R-C-O-H

acid

H-O-R'

alcohol

O
R-C-O-R'

ester

H2O