CYI101
Common CHEMISTRY(Organic)
CYI 101 CHEMISTRY-THEORY (Common) (3-0-0)
UNIT –II
Aromaticity [2L]
Aromatic, non-aromatic and anti-aromatic compounds
Stereochemistry [4L]
Concept of chirality, Axial chirality, enantiomers and diastereomers, specific rotation,
optical purity, Racemic modification and resolution, R/S, D/L and E/Z nomenclature
Pericyclic reactions [4L]
Definitions, Classifications, photochemical [2+2] and thermal [4+2] cycloaddition,
Sigmatropic rearrangement
Macromolecules [4L]
Introduction to peptides and proteins. Basics of Polymer Chemistry, Polymerization
techniques, natural and synthetic polymer
Recommended Books:
1. Organic Chemistry, J. CLayden, N. Greeves, S. Warren, P. Wother, Oxford
University Press, 2000.
2. Principles of polymerization, George G. Odian, 4th Edn, John Wiley & Sons, Inc.,
Publication, 2004.
3. Advanced Organic Chemsitry, Smith & March, 5th Edn, Wiley & Sons
Constitutional Isomers
• Isomers that differ in how their atoms are arranged in chains are
called constitutional isomers
• They must have the same molecular formula to be isomers
Chiral Carbons
• A point in a molecule where four different groups (or atoms) are
attached to carbon is called the chiral carbon
• A chiral molecule usually has at least one chiral carbon
Prochiral Chiral
Important Chiral molecules
Vitamin C
Cholesterol
Amoxicillin Quinine
Anti-Bacterial Anti-malaria
Chiral and Achiral Molecules
• Although everything has a mirror image, mirror images may or
may not be superimposable.
• Some molecules are like hands. Left and right hands are mirror
images, but they are not identical, or superimposable.
• The molecule labeled A and its mirror image labeled B are not
superimposable. No matter how you rotate A and B, all the
atoms never align.
• A and B are stereoisomers—specifically, they are enantiomers.
• A carbon atom with four different groups is a tetrahedral
stereogenic center.
• 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.
Enantiomers have identical chemical and physical properties in an
achiral environment. Enantiomers rotate the direction of plane
polarized light to equal, but opposite angles and interact with other
chiral molecules differently.
The R(+)-isomer, occurring more commonly The less common S(-)-isomer is found in
in nature as the fragrance of oranges, is a mint oils and has a piny, turpentine-like
flavoring agent in food manufacturing. odor.
S-(+)-carvone, has a spicy aroma.
R-(–)-carvone, has a sweetish minty smell,
like spearmint leaves.
Chemical Properties of Enantiomers
• Many drugs are chiral and often must react with a chiral receptor or chiral
enzyme to be effective. One enantiomer of a drug may effectively treat a
disease whereas its mirror image may be ineffective or toxic.
Naproxen
Thalidomide
Thalidomide exists in two mirror-image
forms: it is a racemic mixture of (R)- and
(S)-enantiomers. The (R)-enantiomer,
shown, has sedative effects, whereas
the (S)-isomer is teratogenic.
• Larger organic molecules can have two, three or even more
stereogenic centers.
Diastereomer
Diastereomer
• For a molecule with n stereogenic centers, the maximum number of
stereoisomers is 2n. Let us consider the stepwise procedure for finding
all the possible stereoisomers of 2,3-dibromopentane.
Find and draw all possible stereoisomers for a compound with two stereogenic centers
Step [1] : Draw one stereoisomer by arbitrarily arranging substituents around the stereogenic
centers. Then draw its mirror image.
• Switching the positions of H and Br (or any two groups) on one stereogenic
center of either A or B forms a new stereoisomer (labeled C in this example),
which is different from A and B. The mirror image of C is labeled D. C and
D are enantiomers.
How to, Continued…
• Stereoisomers that are not mirror images of one another are called
diastereomers. For example, A and C are diastereomers.
• Compound C contains a plane of symmetry, and is achiral.
• Meso compounds generally contain a plane of symmetry so that
they possess two identical halves.
• Because one stereoisomer of 2,3-dibromobutane is
superimposable on its mirror image, there are only three
stereoisomers, not four.
Meso Compounds
Physical Properties of Stereoisomers—Optical Activity
• The chemical and physical properties of two enantiomers are
identical except in their interaction with chiral substances. They
have identical physical properties, except for how they interact
with plane-polarized light.
• Plane-polarized (polarized) light is light that has an electric
vector that oscillates in a single plane. Plane-polarized light
arises from passing ordinary light through a polarizer.
• A polarimeter is an instrument that allows polarized light to
travel through a sample tube containing an organic compound.
It permits the measurement of the degree to which an organic
compound rotates plane-polarized light.
• With achiral compounds, the light that exits the sample tube
remains unchanged. A compound that does not change the
plane of polarized light is said to be optically inactive.
• With chiral compounds, the plane of the polarized light is rotated
through an angle . The angle is measured in degrees (°), and is
called the observed rotation. A compound that rotates polarized
light is said to be optically active.
• The rotation of polarized light can be clockwise or
anticlockwise.
• If the rotation is clockwise (to the right of the noon position),
the compound is called dextrorotatory. The rotation is labeled d
or (+).
• If the rotation is counterclockwise, (to the left of noon), the
compound is called levorotatory. The rotation is labeled l or (-).
• Two enantiomers rotate plane-polarized light to an equal extent
but in opposite directions. Thus, if enantiomer A rotates
polarized light +5°, the same concentration of enantiomer B
rotates it –5°.
• No relationship exists between R and S prefixes and the (+) and
(-) designations that indicate optical rotation.
Specific Rotation []D : a standardized value for the optical rotation
= observed rotation in degrees
[]obs l = path length in dm
[]T = c = concentration of sample in g/mL
lxc
T = temperature in °C
= wavelength of light, usually D for the
D-line of a sodium lamp (589 nm)
The specific rotation is a physical constant of a chiral molecule
The []D may also depend upon solvent, therefore the solvent is
usually specified.
H NH2
for alanine: HO2C
[]20
D = +14.5° (c 10, 6N HCl)
• 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 example—If 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.
What is the ee of the following racemic mixture?
95% A and 5% B
ee = % of A - % of B
= 95 – 5 = 90 ee
Given the ee value, what percent is there of each isomer, 60%
ee
60% excess A, then 40% racemic mixture( so 20% A and
20% B)
So, 60% + 20% = 80% A and leaves 20% B
A pure compound has a specific rotation of +24, a solution of
this compound has a rotation of +10, what is the ee?
ee = [] of mixture / [] of pure x 100
=+10/+24 x 100 = 42%
CYI101
Common CHEMISTRY(Organic)
CYI 101 CHEMISTRY-THEORY (Common) (3-0-0)
UNIT –II
Aromaticity [2L]
Aromatic, non-aromatic and anti-aromatic compounds
Stereochemistry [4L]
Concept of chirality, Axial chirality, enantiomers and diastereomers, specific rotation,
optical purity, Racemic modification and resolution, R/S, D/L and E/Z nomenclature
Pericyclic reactions [4L]
Definitions, Classifications, photochemical [2+2] and thermal [4+2] cycloaddition,
Sigmatropic rearrangement
Macromolecules [4L]
Introduction to peptides and proteins. Basics of Polymer Chemistry, Polymerization
techniques, natural and synthetic polymer
Recommended Books:
1. Organic Chemistry, J. CLayden, N. Greeves, S. Warren, P. Wother, Oxford
University Press, 2000.
2. Principles of polymerization, George G. Odian, 4th Edn, John Wiley & Sons, Inc.,
Publication, 2004.
3. Advanced Organic Chemsitry, Smith & March, 5th Edn, Wiley & Sons
Physical properties of enantiomers
The chemical and physical properties of two enantiomers are identical
except in their interaction with chiral substances.
The R(+)-isomer, occurring more commonly The less common S(-)-isomer is found in
in nature as the fragrance of oranges, is a mint oils and has a piny, turpentine-like
flavoring agent in food manufacturing. odor.
S-(+)-carvone, has a spicy aroma.
R-(–)-carvone, has a sweetish minty smell,
like spearmint leaves.
Physical Properties of Stereoisomers—Optical Activity
• The chemical and physical properties of two enantiomers are
identical except in their interaction with chiral substances. They
have identical physical properties, except for how they interact
with plane-polarized light.
• Plane-polarized (polarized) light is light that has an electric
vector that oscillates in a single plane. Plane-polarized light
arises from passing ordinary light through a polarizer.
• A polarimeter is an instrument that allows polarized light to
travel through a sample tube containing an organic compound.
It permits the measurement of the degree to which an organic
compound rotates plane-polarized light.
• With achiral compounds, the light that exits the sample tube
remains unchanged. A compound that does not change the
plane of polarized light is said to be optically inactive.
• With chiral compounds, the plane of the polarized light is rotated
through an angle . The angle is measured in degrees (°), and is
called the observed rotation. A compound that rotates polarized
light is said to be optically active.
• The rotation of polarized light can be clockwise or
anticlockwise.
• If the rotation is clockwise (to the right of the noon position), the
compound is called dextrorotatory. The rotation is labeled d or
(+).
• If the rotation is counterclockwise, (to the left of noon), the
compound is called levorotatory. The rotation is labeled l or (-).
• Two enantiomers rotate plane-polarized light to an equal extent
but in opposite directions. Thus, if enantiomer A rotates
polarized light +5°, the same concentration of enantiomer B
rotates it –5°.
• No relationship exists between R and S prefixes and the (+) and
(-) designations that indicate optical rotation.
Specific Rotation []D : a standardized value for the optical rotation
= observed rotation in degrees
[]obs l = path length in dm
[]T = c = concentration of sample in g/mL
lxc
T = temperature in °C
= wavelength of light, usually D for the
D-line of a sodium lamp (589 nm)
The specific rotation is a physical constant of a chiral molecule
The []D may also depend upon solvent, therefore the solvent is
usually specified.
H NH2
for alanine: HO2C
[]20
D = +14.5° (c 10, 6N HCl)
• 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 example—If 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.
What is the ee of the following racemic mixture?
95% A and 5% B
ee = % of A - % of B
= 95 – 5 = 90 ee
Given the ee value, what percent is there of each isomer, 60%
ee
60% excess A, then 40% racemic mixture( so 20% A and
20% B)
So, 60% + 20% = 80% A and leaves 20% B
A pure compound has a specific rotation of +24, a solution of
this compound has a rotation of +10, what is the ee?
ee = [] of mixture / [] of pure x 100
=+10/+24 x 100 = 42%
Enantiomer
Diastereomer
• Compound C contains a plane of symmetry, and is achiral.
• Meso compounds generally contain a plane of symmetry so that
they possess two identical halves.
Meso-Tataric acid
• Because one stereoisomer of 2,3-dibromobutane is
superimposable on its mirror image, there are only three
stereoisomers, not four.
Active/Inactive Isomer
Case I
Case II
Case III
Case IV
General formulae
If 'n' is even (here n is the number of chiral centres):
Number of Optically active isomers 2n-1
Number of Meso Compounds 2n-2/2
If 'n' is odd (here n is the number of chiral centres):
Number of Optically active isomers 2n-1-2n-1/2
Number of Meso Compounds 2n-1/2
Case IV
Active Meso
Racemic Mixtures
H H
H
HBr H3C
H3C
CH3 CH3 But do we get (R) or (S)?
addition reaction Br
H H
(E)-2-butene 2-bromobutane
achiral chiral
We get both!
CH3 CH3
H3C H3C
H Br Br H
50% (S)-2-bromobutane 50% (R)-2-bromobutane
A 50:50 mixture of 2 enantiomers is called a racemic mixture or a racemate.
Resolution of Enantiomers
mixture of 2
diastereomers
react or somehow associate with: (R)-compound X (R)-compound Y
(R)-compound X
(S)-compound X (R)-compound Y (S)-compound X (R)-compound Y
Separate by some technique (chromatography,
Single crystallization, distillation, etc.)
racemic mixture enantiomer
of enantiomers
(S)-compound X (R)-compound Y (R)-compound X (R)-compound Y
single single
diastereomer diastereomer
somehow remove compound Y
(S)-compound X (R)-compound X
single single
enantiomer enantiomer
Resolution of Enantiomers
Reaction Using Diastereomers to Separate Enantiomers
this nitrogen lone
pair is basic
Me
(R)--methylbenzylamine
this hydrogen H2N O Me
O is acidic
Me
(S)-2-chloroproprionic acid Me O H3N
OH
Cl
Cl
The R,S-diastereomer of the salt
this nitrogen lone
pair is basic
Me
(R)--methylbenzylamine
this hydrogen O Me
is acidic H2N
O Me
O H3N
(R)-2-chloroproprionic acid Me
OH Cl
Cl
The R,R-diastereomer of the salt
separate
O O Me
O Me
acidify
Me Me
Me
OH O H3N
O H3N
Cl Cl
Cl
(R)-2-chloroproprionic acid
O
acidify
Me
OH
Cl (S)-2-chloroproprionic acid
Resolution of (+/-) Alcohol
(-) Brucine
Resolution of (+/-) Amino Acid
CYI101
Common CHEMISTRY(Organic)
CYI 101 CHEMISTRY-THEORY (Common) (3-0-0)
UNIT –II
Aromaticity [2L]
Aromatic, non-aromatic and anti-aromatic compounds
Stereochemistry [4L]
Concept of chirality, Axial chirality, enantiomers and diastereomers, specific rotation,
optical purity, Racemic modification and resolution, R/S, D/L and E/Z nomenclature
Pericyclic reactions [4L]
Definitions, Classifications, photochemical [2+2] and thermal [4+2] cycloaddition,
Sigmatropic rearrangement
Macromolecules [4L]
Introduction to peptides and proteins. Basics of Polymer Chemistry, Polymerization
techniques, natural and synthetic polymer
Recommended Books:
1. Organic Chemistry, J. CLayden, N. Greeves, S. Warren, P. Wother, Oxford
University Press, 2000.
2. Principles of polymerization, George G. Odian, 4th Edn, John Wiley & Sons, Inc.,
Publication, 2004.
3. Advanced Organic Chemsitry, Smith & March, 5th Edn, Wiley & Sons
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).
• If two atoms on a stereogenic center are the same,
assign priority based on the atomic number of the atoms
bonded to these atoms. One atom of higher atomic
number determines the higher priority.
• 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:
Tritium (T) > Deuterium (D)> Hydrogen (H)
• 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:
6
Cis (Z) Precedes trans (E)
“R” Precedes “S”
Labeling Stereogenic Centers with R or S
Assign R or S to a Stereogenic Center
Example: Label each enantiomer as R or S
Step [1]
Labeling Stereogenic Centers with R or S
Step [2] : Orient the molecule with the lowest priority group (4)
back (on a dash), and
visualize the relative positions of the remaining three groups
(priorities 1, 2 and 3).
For each enantiomer of 2-butanol, look toward the lowest priority group, drawn behind the plane, down
the C-H bond .
Step [3] : Trace a circle from priority group 1 2 3
If tracing the circle goes in the clockwise direction-to the right form the noon position-the isomer is named R
If tracing the circle goes in counterclockwise direction-to the left from the noon position-the isomer is named S
Quick Test
(S) (S) (R)
(R) (R) (S)
Quick Test
Z E
E
Z E
Z
CYI-101
Common-CHEMISTRY(Organic)
CYI 101 CHEMISTRY-THEORY (Common) (3-0-0)
UNIT –II
Aromaticity [2L]
Aromatic, non-aromatic and anti-aromatic compounds
Stereochemistry [4L]
Concept of chirality, Axial chirality, enantiomers and diastereomers, specific rotation,
optical purity, Racemic modification and resolution, R/S, D/L and E/Z nomenclature
Pericyclic reactions [4L]
Definitions, Classifications, photochemical [2+2] and thermal [4+2] cycloaddition,
Sigmatropic rearrangement
Macromolecules [4L]
Introduction to peptides and proteins. Basics of Polymer Chemistry, Polymerization
techniques, natural and synthetic polymer
Recommended Books:
1. Organic Chemistry, J. CLayden, N. Greeves, S. Warren, P. Wother, Oxford
University Press, 2000.
2. Principles of polymerization, George G. Odian, 4th Edn, John Wiley & Sons, Inc.,
Publication, 2004.
3. Advanced Organic Chemsitry, Smith & March, 5th Edn, Wiley & Sons
Axial Chirality
Axial chirality refers to stereoisomerism resulting from the non-
planar arrangement of four groups in pairs about a chiral axis.
Axial chirality is encountered in:
allenes
ortho-substituted biphenyls
Spiro compounds
1,7-dioxaspiro[5.5]undecane
Allenes
The central carbon of allene forms two sigma bonds and two pi bonds. The
central carbon is sp-hybridized and the two terminal carbons are sp2-hybridized.
The two π-bonds attached to the central carbon are perpendicular to each other.
The geometry of the π-bonds causes the groups attached to the end carbon
atoms to lie in perpendicular plane
Since the geometry of the cumulated π-bonds causes the groups at the terminal
carbons to lie in perpendicular planes, allenes that are unsymmetrically substituted on
both ends are chiral.
Note that allenes with odd numbers of cumulated bonds are not chiral; only those
with even numbers are.
Chirality of Allenes
4
Rear d
Front b 2 1
3
a> b> c>d
Front group Precedes the rear group (Group at back)
3
1
2
4
Biphenyl System
Biphenyls are compounds whereby a phenyl ring is connected to another
through a central σ bond.
In unsubstituted biphenyl, there is sufficient amount of freedom of
rotation around the central single bond to allow for free inter conversion
between the various conformers or rotamers so that the various
rotamers can not exist independently.
Biphenyl Systems (Atropisomerism)
The biphenyls with large substituents at the ortho positions on either side
of the central σ bond experience restricted rotation along this bond due to
steric hindrance.
If the substituents are different, a chiral molecule existing as a pair of
enantiomers called atropisomers
Polynuclear aromatic systems e.g. binol
also exist as enantiomers.
BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl)
BINAP
BINAP is used in organic synthesis for enantioselective transformations catalyzed by
its complexes of ruthenium, rhodium, and palladium As pioneered by Ryōji Noyori and
his co-workers, rhodium complexes of BINAP are useful for the synthesis of (–)-
menthol.
He won the Nobel Prize in Chemistry in 2001, for the
study of chirally catalyzed hydrogenations
(-) Menthol
Chirality of Biphenyl Systems
Assigning Configurations of Atropisomers (Ra vs Sa)
The subscript “a” referring to “axially chiral”
By generating appropriate models of each atropisomer, the sense of configuration can be
determined.
a> b> c>d
(R)-methyl 2'-methoxy-6-nitro-[1,1'-biphenyl]-
2-carboxylate
(R)-[1,1'-binaphthalene]-2,2'-diol
Assign the configuration of Allenes
(S)-3-chloro-1-fluorobuta-1,2-diene
(S)-1,3-diphenylpropa-1,2-diene
(R)-1,3-dichloropropa -1,2-diene