CML100 Introduction to Chemistry; Semester II, 2018-2019

Course contents
Entropy and free energy changes in chemical processes, Chemical equilibria, Phase
transformations, Structure and dynamics of microscopic systems, Physical basis of atomic and
molecular structure, Three-dimensional arrangement of atoms in molecules, Structure and
reactivity of organic, inorganic and organometallic compounds, Basic strategies for synthesis of
carbon and silicon containing compounds, Coordination chemistry, Role of inorganic chemistry in
living systems.
Course instructors: This is a two-section class. Both sections meet on Tuesday, Wednesday, and
Friday - the morning class at 9 am (LH 114) and the afternoon one at 2 pm (LH 114).
Prof. N. Kurur: Physical Chemistry (Office # MS 733 (II-G2), Phone +91 11 2659-1378) Prof. S.
Paria: Inorganic Chemistry (Office # MS 726, Phone +91 11 2659-6499) Prof. S. L. Gholap:
Organic Chemistry (Office # MS 721, Phone +91 11 2659-1316) Course coordinator: Prof.
Shivajirao L. Gholap
References:
(1) A. J. Elias, Basic Organometallic Chemistry, Universities Press; (2) P. W. Atkins, J. de Paula,
Physical Chemistry, Oxford; (3) D. A. McQuarrie and J. D. Simon, Physical Chemistry, Viva; (4) J. E.
Huheey, E. L. Keiter, R. L. Keiter, O. K. Medhi, Inorganic Chemistry, Pearson; (5) Clayden, Greeves,
Warren and Wothers, Organic Chemistry; (6) R. T. Morrison and R. N. Boyd, Organic Chemistry,
Pearson; (7) D. G. Morris, Stereochemistry, OUP.
 CML100 Introduction to Chemistry; Semester II, 2018-2019

Attendance policy: If your attendance is less than 75%, you will be awarded 1
grade less than the actual grade that you earn.

Exams and Evaluation

• There will be two minor exams of 20 marks each (2×20) = 40 marks.
• One major exam of 40 marks. (20 marks each from Physical and Organic)
• 20 marks are allocated to 8 assignments that will be provided by the
instructors from time to time.
• Minor and Major exams will be re-taken only for medical reasons, when
supported by a medical certificate.

Re-minor 20 April – 25 April (20 Marks) All syllabus

Major 29 April (Monday) 1:00-3:00 pm LH 121, LH 325, LH 512, LH 526, LH 527

 What is organic chemistry?
• Chemistry of Carbon, Study of carbon compounds it makes, and the reactions it
undergoes. The study of hydrocarbons (compounds of hydrogen and carbon) and
their derivatives.
• We used to describe organic chemistry as the chemistry of living things.
• over 16 million carbon-containing compounds are known (Animal and plant
matter, Foods, Pharmaceuticals, Cosmetics, Fertilizers, Plastics, Petrochemicals,
Clothing)
• The C-C single bond (348 kJ mol-1) and C-H bond (412 kJ mol-1) are strong,
carbon compounds are stable
• Since the chemistry of living things is based on carbon, the chemistry of carbon
compounds has come to be known as organic chemistry.
• There are two important properties of carbon that
make it a suitable element to form the
compounds in living things:
• Firstly, carbon atoms can link together to form
stable chains of great length.
• Carbon atoms bind strongly to each other and
form very large molecule which are built around
this carbon 'backbone’.
• The unique strong covalent bonds: Strong
single, Double and Triple bonds
 Three Types of Carbon Backbones

Carbon forms long chains

• One carbon chain may contain hundreds of carbon atoms.

• Unlike other elements, carbon atoms can bond to each other to form very long chains.
• A very large carbon-based molecule made of repeating units is called a polymer.
Each unit of a polymer is called a monomer.
• Polymers can be thousands of atoms long
 Carbon forms Rings
• When there are three or more carbons in a straight chain, the ends can be
joined to make rings.
• Carbon-based molecules also can be shaped like rings. Most carbon rings
contain 5 or 6 carbon atoms.

• One of the most important carbon rings is benzene.

• It has 6 carbons & 6 hydrogens , with alternating double bonds.

• They often have very strong smells or aromas, so they are called aromatic
compounds.
 What makes carbon so special?
• It has a “central” role in all living organisms.
• It has 4 valence electrons.
• It makes 4 covalent bonds.
• It can bond with any element, but really loves to bond with other
carbon atoms and make long chains
H
C H
H
H
 Hydrocarbons
Hydrocarbons are organic compounds that are made of only hydrogen and carbon
atoms. They are found in many places, including crude oil and natural gas.
 Hydrocarbons

Alkanes C C Molecular formula Alkenes C C

Shows atoms in the
H H H H H molecule H H H
H C C C C C H H C C C C C H
Structural formula
H H H H H Shows how they are all H H H H H
connected
C5H12 C5H10

Saturated:
Alkynes C C single bond present
Aromatics
H
H H H H C H
C C
Unsaturated: double
H C C C C C H C C
or H C H
H H H triple bond present
H
C5H8 C6H6
Alkanes
Naming Alkanes
 Naming Alkanes Substituents
• Substituents such as —CH3 and —CH2CH3, that branch off the main
chain are called alkyl groups.
• Methyl group: —CH3 Ethyl group: —CH2CH3
 Properties of Alkanes
• Alkanes contain only nonpolar C–C and C–H bonds. The only intermolecular
forces influencing them are weak London dispersion forces.
• The effect of these forces is shown in the regularity with which the melting and
boiling points of straight-chain alkanes increase with molecular size.
– The first four alkanes, methane, ethane, propane, and butane, are gases at
room temperature and pressure.
– Alkanes with 5–15 carbon atoms are liquids.
– Alkanes with 16 or more carbon atoms are low-melting, waxy solids.
• They are typical covalent compounds, nonpolar, insoluble in water but able to
mix with each other, soluble in nonpolar organic solvents.
• Alkanes are generally less dense than water, they float on its surface, ,
Flammable, otherwise not very reactive.
• Mineral oil, petroleum jelly, and paraffin wax are mixtures of higher alkanes. All
are harmless to body tissue and are used in numerous food and medical
applications.
• Odorless or mild odor, colorless, tasteless, nontoxic.
 Cycloalkanes
• When there are three or more carbons in a straight chain, the ends can be
joined to make rings.
• In naming these molecules, the prefix cyclo- is used to indicate the ring: Skeletal
structural formulas are used to represent the rings in structural formulas:

As Parent Chain As Substituent Group

C3H6
cyclopropane R cyclopropyl-

C4H8

cyclobutane R cyclobutyl-

C5H10

cyclopentane R cyclopentyl-

C6H12
R
cyclohexane cyclohexyl-
 Cycloalkanes
• A cycloalkane is an alkane that contains a ring of carbon atoms.
• To form a closed ring requires an additional C–C bond and the loss of 2 H atoms.
• The general formula for cycloalkanes is CnH2n.
• Compounds of ring sizes from 3 through 30 and beyond have been prepared in
the laboratory.

➢ The C–C–C bond angles in cyclopropane are 60, and the bond angles in
cyclobutane are 90, much less than the ideal 109.5° tetrahedral angle.
➢ These compounds are less stable and more reactive than other cycloalkanes.
 The Nature of Organic Molecules
• Carbon is tetravalent; it always forms four covalent bonds.
• Organic molecules have specific three-dimensional shapes.
• When carbon bonds to a more electronegative element, polar covalent
bonds result.

Chloromethane, CH3Cl

In a tetrahedral molecular geometry, a

central atom is located at the center with
four substituents that are located at the
corners of a tetrahedron.
The bond angles 109.5°
 The Structure of Organic Molecules: Alkanes and Their Isomers
• There are two ways in which molecules that have the formula C4H10 can be
formed.

A condensed structure is a shorthand way of drawing structures in which C–C and C–H
bonds are understood rather than shown.
 The Nature of Organic Molecules
• Organic molecules often contain nitrogen and oxygen in addition to carbon and
hydrogen.
– Nitrogen can form single, double, and triple bonds to carbon.
– Oxygen can form single and double bonds.
– Hydrogen can only form single bonds to carbon.

• Covalent bonding
– Lower melting and boiling points than inorganic salts
– Many organic compounds are liquids or low melting solids at room
temperature, and a few are gases.
– Most organic compounds are insoluble in water.
– Only Polar organic molecules dissolve in water.
 Properties of Alkanes
• Alkanes contain only nonpolar C–C and C–H bonds. The only intermolecular
forces influencing them are weak London dispersion forces.
• The effect of these forces is shown in the regularity with which the melting
and boiling points of straight-chain alkanes increase with molecular size.
– The first four alkanes, methane, ethane, propane, and butane, are gases
at room temperature and pressure.
– Alkanes with 5–15 carbon atoms are liquids.
– Alkanes with 16 or more carbon atoms are low-melting, waxy solids.
• Alkanes are insoluble in water but soluble in nonpolar organic solvents.
• Alkanes are generally less dense than water, they float on its surface.
• Mineral oil, petroleum jelly, and paraffin wax are mixtures of higher alkanes.
All are harmless to body tissue and are used in numerous food and medical
applications.
• Odorless or mild odor, colorless, tasteless, nontoxic
• Nonpolar, insoluble in water but soluble in nonpolar organic solvents, less
dense than water, Flammable, otherwise not very reactive
Families of Organic Molecules: Functional Groups

• “A functional group is an atom, group of atoms or bond that gives a molecule a

particular set of chemical and physical properties”

• Organic compounds can be classified into families according to structural

features.

• The chemical behavior of family members is often predictable based on their

specific grouping of atoms.

• The chemistry of an organic molecule is primarily determined by the functional

groups it contains, not by its size or complexity.
Summary of Important Families of Organic Compounds
Summary of Important Families of Organic Compounds
 Stereochemistry Chemistry in three dimensions
The branch of chemistry concerned with
the three-dimensional arrangement of
atoms and molecules and the effect of this
on chemical reactions.

Isomers are the different

compounds with the
same molecular formula.
 Review of Isomerism
• Isomers – Compounds that have the same molecular formula but do not have identical
structures (Different structural formula).
• Constitutional Isomers – differ in the way their atoms are connected.
• Stereoisomers –compounds with the same connectivity, different arrangement in space.
Constitutional Isomers and Stereoisomers
Compounds with same molecular formula
Definitions
➢Stereoisomers – The compounds with the same connectivity, different
arrangement in space.

➢ Enantiomers – stereoisomers that are non superimposible mirror images; only

properties that differ are direction (+ or -) of optical rotation.

➢Diastereomers – stereoisomers that are not mirror images; different compounds

with different physical properties.
•Geometric isomers (cis-trans) and Molecules with 2 or more chiral carbons.

Asymmetric center or chiral center– sp3 carbon with 4 different groups attached

Optical activity – the ability to rotate the plane of plane polarized light

Chiral compound – a compound that is optically active (achiral compound will

not rotate light)

Polarimeter – device that measures the optical rotation of the chiral compound
Diastereomers: Geometric isomers (cis-trans)
• With rings and with C=C double bonds, cis-trans notation is used to distinguish
between stereoisomers
• Cis – identical groups are positioned on the SAME side of a ring
• Trans – identical groups are positioned on OPPOSITE sides of a ring

• C-C bonds that are constrained in a cyclic structure can not freely rotate
• To maintain orbital overlap in the pi bond, C=C double bonds can not freely rotate.
Diastereomers: Geometric isomers (cis-trans)
Alkenes: Cis-trans isomers are not mirror images, so these are diastereomers.
H H H CH3
C C C C
H3C CH3 H3C H
cis-2-butene trans-2-butene

▪ Differ in the arrangement of their atoms in space (cannot interconvert)- Alkenes.

Ring Compounds: Cis-trans isomers possible. May also have enantiomers.

Example: trans-1,3-dimethylcylohexane
 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.

•A molecule or object that is superimposable on its mirror image is said to

be achiral.
•A molecule or object that is not superimposable on its mirror image is
said to be chiral.
 Chirality
➢Chiral: an object that is not superimposable on its mirror image
➢Achiral: an object that lacks chirality; one that lacks handedness
• We can now consider several molecules to determine whether or not they
are chiral.
 Chirality
• The molecule labeled A and its mirror image labeled B are
not superimposable therefore A and B are different
compounds.
• A and B are not superimposable stereoisomers, specifically,
they are called enantiomers.
• A carbon atom with four different groups is a tetrahedral
stereogenic center or chiral center.
 Chiral Center or Stereogeniccenter
➢ The most common (but not the only) cause of chirality in organic
molecules is a tetrahedral atom, most commonly carbon, bonded to four
different groups
➢ To locate a stereogenic center, examine each tetrahedral carbon atom in
a molecule, and look at the four groups, not the four atoms, bonded to it.
➢ A carbon with four different groups bonded to it is called a chiral center or
stereogenic center.
• Always omit from consideration all C atoms that cannot be tetrahedral
stereogenic centers. These include
CH2 and CH3 groups
Any sp or sp2 hybridized C
 Chiral center or Asymmetric center
• An asymmetric center is an atom that is bonded to four different
groups.
 Chirality
• In general, a molecule with no stereogenic centers will not be
chiral.
• With one stereogenic center, a molecule will always be chiral.
• With two or more stereogenic centers, a molecule may or may
not be chiral.
• An achiral object has at least one element of symmetry, but chiral
molecules do not.
❑ Plane of symmetry: an imaginary plane passing through an
object dividing it so that one half is the mirror image of the
other half
❑ Center of symmetry: a point so situated that identical
components are located on opposite sides and equidistant
from that point along the axis passing through it
 Chirality
• An achiral object has at least one element of symmetry, but chiral
molecules do not.
❑ Plane of symmetry: an imaginary plane passing through an
object dividing it so that one half is the mirror image of the other
half
❑ Center of symmetry: a point so situated that identical
components are located on opposite sides and equidistant from
that point along the axis passing through it
Summary of the Basic Principles of Chirality:

• Everything has a mirror image. The fundamental question is

whether the molecule and its mirror image are
superimposable.
• If a molecule and its mirror image are not superimposable,
the molecule and its mirror image are chiral.
• The terms stereogenic center and chiral molecule are related
but distinct. In general, a chiral molecule must have one or
more stereogenic centers.
• The presence of a Plane of symmetry or Center of symmetry
makes a molecule achiral.
 Chiral or Achiral?
• 2-butanol Asymmetric
center

➢ 2-bromopropane

chiral mirror image

A chiral compound and its mirror image are
called enantiomers

achiral
Isomers with one asymmetric center

Draw enantiomers
 Enantiomers
• Asparagine: mirror
plane

O OH HO O
C C

H2N C H H C NH2

CH2 CH2
C C
H2N O O NH2

L-asparagine (from D-asparagine (from

asparagus) bitter vetch) sweet taste
taste

enantiomers
Naming enantiomers:
Absolute Configuration (R) ("Rectus" → Latin= "right"). and (S)
"Sinister" → Latin= "left”) Configuration.

• Both enantiomers of alanine receive the same name in the IUPAC

system: 2-aminopropanoic acid.
• Only one enantiomer is biologically active. In alanine only the
enantiomer on the left can be metabolized by the enzyme.
• A way to distinguish between them is to use stereochemical modifiers
(R) and (S).
 Absolute Configuration
❑(R) and (S) Configuration
– Assign priorities to the remaining groups based on atomic numbers.
– Clockwise (highest to lowest priority)  R
– Counterclockwise (lowest to highest priority)  S

CH 2CH3 1 2
OH HO CH2CH3
H C = C (R)-2-butanol
CH3 CH3
3
 Cahn–Ingold–Prelog Priority System
• Cahn–Ingold–Prelog convention is the most widely accepted
system for naming the configurations of chirality centers.

• Enantiomers have different spatial arrangements of the four

groups attached to the asymmetric carbon.

• The two possible spatial arrangements are called

configurations.

• Each asymmetric carbon atom is assigned a letter (R) or (S)

based on its three-dimensional configuration.
 (R) and (S) Configuration: Step 1 Assign Priority
• Assign a relative “priority” to each group bonded to the asymmetric
carbon. Group 1 would have the highest priority, group 2 second, etc.
• Atoms with higher atomic numbers receive higher priorities.
I > Br > Cl > S > F > O > N > 13C > 12C > 2H > 1H
Atomic number: F > N > C > H

(R) and (S) Configuration: Breaking Ties

In case of ties, use the next atoms along the chain of each group as
tiebreakers.
 (R) and (S) Configuration: Multiple Bonds

Treat double and

triple bonds as if
each were a bond to
a separate atom.
 (R) and (S) Configuration: Step 2

• Working in 3-D, rotate the

molecule so that the lowest
priority group is in back.

• Draw an arrow from highest (1) to

second highest (2) to lowest (3)
priority group.

• Clockwise = (R),
Counterclockwise = (S)
Examples
3
CH3

1
CH3CH 2CH=CH H4
CH2CH 2CH2CH3
2
Counterclockwise
Counterclockwise (S)
(S)
Clockwise
3
(R)
1 CH 2CH3
OH
rotate
C 3 2
C 4
2 CH2CH 3 CH3CH 2CH2 H
CH3CH 2CH2
H OH
4 1
Configuration in Cyclic Compounds
• Determine the absolute configuration of the following compounds:
• Determine the absolute configuration of the following compounds:
• Determine the absolute configuration of the following compounds:
 Absolute Configuration Examples
• Determine the absolute configuration of the following compounds:
 Enantiomers and Diastereomers
❑ Molecules with more than one chirality center have mirror image stereoisomers
that are enantiomers
❑ In addition they can have stereoisomeric forms that are not mirror images, called
diastereomers

Diastereomers
 Meso Compounds

• Tartaric acid has two chirality centers

and two diastereomeric forms
• One form is chiral and the other is
achiral, but both have two chirality
centers
• An achiral compound with chirality
centers is called a meso compound –
it has a plane of symmetry
• The two structures on the right in the
figure are identical so the compound
(2R, 3S) is achiral
 Meso
Enantiomers
Racemic Mixtures & Resolution of Enantiomers

• A 50:50 mixture of two chiral compounds that are mirror images

does not rotate light – called a racemic mixture (named for
“racemic acid” that was the double salt of (+) and (-) tartaric acid

• The pure compounds need to be separated or resolved from the

mixture (called a racemate)
• To separate components of a racemate (reversibly) we make a
derivative of each with a chiral substance that is free of its
enantiomer (resolving agent)
• This gives diastereomers that are separated by their differing
solubility
• The resolving agent is then removed
Resolution of Enantiomers

Inseparable
by normal
extraction
techniques
due to
identical
chemical
properties
Resolution of Enantiomers

Separable
by normal
extraction
techniques
due to
different
chemical
properties
Physical Properties of Stereoisomers—Optical Activity

• The chemical and physical properties of two enantiomers are

identical (Same boiling point, melting point, and density) except in
their interaction with chiral substances. Enantiomers may have
different smells, taste.

• Rotate the plane of polarized light in the same magnitude, but in

opposite directions.

• 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.
 Optical Activity
• Optical Activity – The ability of a compound to rotate the plane of polarized
light.
• A compound that rotates the plane of polarization is said to be optically active.
• Chiral compounds are optically active; achiral compounds are optically inactive.
• A polarimeter is used to make such measurements.

• 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.
 Optical Activity Chiral compounds are optically active
• Plane-polarized light is produced by passing normal light through a polarizer. A
polarizer or polariser is an optical filter that lets light waves of a specific
polarization pass and blocks light waves of other polarizations. It can convert a
beam of light of undefined or mixed polarization into a beam of well-defined
polarization, that is polarized light.

• When plane-polarized light passes through a solution of achiral molecules,

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.
Optical Activity
However, when plane-polarized
light passes through a solution of
a chiral compound, 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.
Physical Properties of Stereoisomers Racemic Mixtures

• An equal amount of two enantiomers is called a racemic

mixture or a racemate. A racemic mixture is optically inactive.
Because two enantiomers rotate plane-polarized light to an
equal extent but in opposite directions, the rotations cancel,
and no rotation is observed.
 Specific rotation

• Specific rotation is a standardized physical constant for the

amount that a chiral compound rotates plane-polarized light.
Specific rotation is denoted by the symbol [] and defined
using a specific sample tube length (l, in dm), concentration
(c in g/mL), temperature (25 0C) and wavelength (589 nm).
Physical Properties of Stereoisomers—Optical Purity

• 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.
• Since enantiomers have identical physical properties, they cannot be
separated by common physical techniques like distillation.
• Diastereomers and constitutional isomers have different physical
properties, and therefore can be separated by common physical
techniques.

The physical properties of

the three stereoisomers
of tartaric acid
Example: A compound was isolated in the lab and the
observed roation was +10 when measured in a 1 dm.
tube containing 1.0 g of sample in 10 mL of water. What
is the specific rotation of this compound?

[] = /(length x (g/ml));

[] = 10/(1dm. X (1.0g/10ml)) = +100

Example: What is the ee of the given racemic mixture?

95% A and 5% B
ee = % of A - % of B
= 95 – 5 = 90 ee
Example: 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

Example: 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%
 Specific Rotation and Molecules
• Characteristic property of a compound that is optically active the
compound must be chiral

• The specific rotation of the enantiomer is equal in magnitude but

opposite in sign

71
Chemical Properties of Enantiomers

• Two enantiomers have exactly the same chemical properties except for
their reaction with chiral non-racemic reagents.
• 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.
 Fischer Projections
• Flat drawing that represents a 3D molecule
• A chiral carbon is at the intersection of horizontal and vertical lines.
• Horizontal lines are forward, out-of-plane.
• Vertical lines are behind the plane.
➢ Fischer Rules
➢ Carbon chain is on the vertical line.
➢ Highest oxidized carbon at top.
➢ Rotation of 180 in plane doesn’t change molecule.
➢ Do not rotate 90!’
(R)-(+)-glyceraldehyde

(S)-(-)-glyceraldehyde
 Fischer Mirror Images
• Easy to draw, easy to find enantiomers, easy to find internal mirror planes.
• Examples:
CH3 CH3 CH3
H Cl Cl H H Cl
Cl H H Cl H Cl
CH3 CH3 CH3

Fischer (R) and (S)

(S)
CH3
➢ Lowest priority (usually H) comes forward,
so assignment rules are backwards! H Cl
➢ Clockwise 1-2-3 is (S) and
counterclockwise 1-2-3 is (R).
Cl H
CH3
(S)
Assigning R and S Configuration to Fischer Projections

1. Assign priorities to the four substituents according to the Cahn-Ingold-

Prelog rules
2. Perform the two allowed manipulations of the Fischer projection to place
the lowest priority group at the top or bottom.
3. If the priority of the other groups 1→2→3 is clockwise then assign the
carbon as R, if priority of the other groups 1→2→3 is counterclockwise
then assign the center as S.
2
place at
CO2H the top 4
H
1 H2N H 4 2 HO2C NH2 1
hold steady CH3
CH3
rotate other 3 3
three groups
counterclockwise
1-2-3 counterclockwise = S
2
4 2
CO2H
H CO2H
4 H 1 2
NH2 1 H2N
H2 N CO2H CH3
CH3 1 3
CH3 H
3 4
3

1-2-3 clockwise = R
Fischer projections with more than one chiral center:

(2S)

(3R)
Draw Fischer Projections given chiral compounds

CH3

HO
H2N CH3 Cl H

H OH NH2

H3C Cl
CH3

H OH H Cl
Cl H

HO Cl
H3C CH3
HO H
HO Cl
 Assigning R and S Configuration to Fischer Projections

CH3

R
F OH S
S
S
Cl H
S
R
CH3
R
S

R
 Question Draw the Fischer of the following molecules

A HO
H A HO H

F H
F
H

F OH
B H D
D H
B
H Cl

Cl H HO F

HO F

F HO Cl OH
C Cl H
C
HO Cl

I F
H Cl F I
 Conformers of Alkanes
• Structures resulting from the free rotation of a C-C single bond
or Different arrangement of atoms resulting from bond rotation
• May differ in energy. Molecules constantly rotate through all
the possible conformations.
Conformations can be represented in 2 ways:
 Conformers of Alkanes
• We do not observe perfectly free rotation
• There is a barrier to rotation, and some conformers are more stable than others
• Staggered- most stable: all 6 C-H bonds are as far away as possible
• Eclipsed- least stable: all 6 C-H bonds are as close as possible to each other

H H H H
H
H H H
H H H H H H
H H H H HH HH
H H

sawhorse Newman sawhorse Newman

staggered eclipsed
 Conformations of ethane

ethane
Staggered Eclipsed
conformation conformation
of ethane of ethane

Newman Sawhorse Newman Sawhorse

Projection Representation Projection Representation
Conformations of Butane

butane
Staggered Eclipsed
conformation conformation
of butane of butane
Newman and Sawhorse projection

CH3
HH HH H H
Newman projection

H H
H3C CH3
CH3
H H H H

CH3 Sawhorse projection

H H CH CH3
3

H H
CH3

Eclipsed Staggered
 Interconversions

Fischer Sawhorse

COOH H OH
H OH

H OH
 H
OH COOH

COOH COOH
 Interconversions

Sawhorse Fischer

H CH3
Br


H Br
Br
H CH3 Br H

CH3 CH3
 CH2OH H
H
Cl

H Cl
H Br
CHO
CHO CH2OH
Fischer Newman
H Cl

H CH2OH
Br

CHO Sawhorse
 Ethane Conformers
➢ Staggered conformer: Lowest energy; Dihedral angle = 60
➢ Eclipsed conformer has highest energy; Dihedral angle = 0
 Conformational Analysis
• Torsional strain: resistance to rotation.
• For ethane, only 3.0 kcal/mol
 Propane Conformers
Note slight increase in torsional strain due to the more bulky methyl group.
 Butane Conformers

• Highest energy has methyl groups eclipsed.

• Steric hindrance
• Dihedral angle = 0 degrees

totally eclipsed
 Butane Conformers
• Lowest energy has methyl groups anti.
• Dihedral angle = 180 degrees

anti
• Methyl groups eclipsed with
hydrogens
• Higher energy than
staggered conformer
• Dihedral angle = 120 degrees
eclipsed

• Gauche, staggered conformer

• Methyls closer than in anti
conformer
• Dihedral angle = 60 degrees
gauche
Conformational Analysis
 Cycloalkanes and their Stereochemistry
• Saturated cyclic hydrocarbons are defined as a carbon ring which has hydrogen in
every position except the attachment point. These are also called alicyclic compounds.
H H
H H Cyclopropane
H
H H H H Cyclo = the cyclic ring
H
H H propane = the number of carbons

Basic Examples of Cycloalkanes

3 4 5 6 7 8 9 10

Prop But Pent Hex Hept Oct Non Dec

Example: Cyclohexane = a ring of six carbons

 Naming Cycloalkanes
➢ Rule 1 Find the parent: Count the number carbons in the chain and the
substituents. If the substituents is longer than the ring then the parent name is
the substituent. If the ring is longer then the ring is the parent.

1-Methylcyclopentane 1-Cyclopropylbutane

• If we look at the molecule on the left. A pentane ring has 5 carbons compared to
its substituent (1 carbon) a methyl. So the parent is the cyclopentane. However
on the molecules on the right butane (4 carbons) is larger than cyclopropane (3
carbons) so the butane is the parent name.

➢ Rule 2: Number the substituents, and write the name.

• Make sure that you follow the ring so that the substituents have the lowest
numbers.
• Number the Substituents. C-1 always has a substituent attached. Number so that
the second substituent has the lowest number possible, etc,
 CH3
1,2,4-
4
3
trimethylcyclopentane
5

1 2 Not 1,3,4-
H3C CH3 trimethylcyclopentane
 ➢ Rule 3: If two or more alkyl groups have potentially the same number,
number alphabetically.

CH3 1-ethyl-2-
CH2CH3 methylcyclohexane

Not 1-methyl-2-
ethylcyclohexane

➢ Rule 4: Treat other substituents exactly like alkyl groups.

CH3
Br

1-Bromo-2-methylcyclohexane
Example for practice:
 Cis-Trans Isomerism in Cycloalkanes

• Cycloalkanes are less flexible than open-chain alkanes

• Much less conformational freedom in cycloalkanes
➢ Because of their cyclic structure, cycloalkanes have 2 faces as viewed edge-
on “top” face “bottom” face
➢ Because ring don’t rotate freely in space like linear chains two different
possibilities exist.
➢ Cis Isomers are when two atoms are on the same side of a ring.
➢ Trans Isomers are when two atoms are on different side of a ring.

H
H
H
H
H H H
H

Cis Isomers Trans Isomers

 Ring Strain in Cycloalkanes
Types of Strain

• Angle Strain or Ring Strain is the strain induced in a molecule when

the bond angles are different from the ideal tetrahedral bond angle
of 109.5. (expansion or compression of bond angles.)

• Torsional Strain – is caused by repulsion between the bonding

electrons of one substituent and the bonding electrons of a nearby
substituent.

• Steric Strain –is caused by atoms or groups of atoms approaching

each other too closely.
 Angle (Ring) Strain

• Cyclopropane has angles of 60o when we know that SP3 carbons

like to bond at 109.5o. In cyclopropane there is angle strain.

• expansion or compression of bond angles away from most stable

• Example cyclopropane and cyclohexane:

o
60o ~109.5
 Torsional Strain
• Is the strain due to eclipsing of bonds on neighboring atoms.
• When atoms are eclipsed then there is a natural tendency to
move away from each other this is called torsional strain.

H H
H H H H
H
H H H H
H H H
H
H H H
 Steric Strain
• Steric strain focuses on the strain of functional groups bound due to
size onto the cyclic ring. Because rings don’t rotate freely in space
like linear chains then energy is higher when they are on the same
side.
• repulsive interactions between nonbonded atoms in close proximity
• For example: cyclopropane

H
H
H
H
H H H
H
Higher Energy Lower Energy
 Stability of Cycloalkanes: Ring Strain
• Rings larger than 3 atoms are not flat
• Cyclic molecules can assume nonplanar conformations to minimize
angle strain and torsional strain by ring-puckering
• Larger rings have many more possible conformations than smaller
rings and are more difficult to analyze
The Study of Chemical Reactions
▪ Overall reaction: reactants → products
▪ Mechanism: Step-by-step pathway.
▪ To learn more about a reaction:
Thermodynamics
Kinetics
 Understanding Organic Reactions

Writing Equations for Organic Reactions

• Equations for organic reactions are usually drawn with a single reaction arrow (→)
between the starting material and product.
• The reagent, the chemical substance with which an organic compound reacts, is
sometimes drawn on the left side of the equation with the other reactants. At other
times, the reagent is drawn above the arrow itself.
• Although the solvent is often omitted from the equation, keep in mind that most
organic reactions take place in liquid solvent.
• The solvent and temperature of the reaction may be added above or below the
arrow.
• The symbols “h” and “” are used for reactions that require light and heat
respectively.
 Different ways of writing organic reactions

• When two sequential reactions are carried out without drawing any intermediate compound, the steps are
usually numbered above or below the reaction arrow.
Understanding Organic Reactions
Types of Organic Reactions

1) Substitution Reactions

2) Elimination Reactions

3) Addition Reactions

4) Rearrangement Reactions
 Substitution Reactions
• A substitution is a reaction in which an atom
or a group of atoms is replaced by another
atom or group of atoms.
• In a general substitution, Y replaces Z on a
carbon atom.

• Substitution reactions involve  bonds: one  bond breaks and another forms at the same carbon
atom.
 Elimination Reactions
• Elimination is a reaction in which
elements of the starting material are “lost”
and a  bond is formed.
( X and Y are detached from two different carbon
atoms that are vicinal to each other)

• In an elimination reaction, two groups X

and Y are removed from a starting
material.

• Two  bonds are broken, and a  bond is

formed between adjacent atoms.

• The most common examples of

elimination occur when X = H and Y is a
heteroatom more electronegative than
carbon.
 Addition Reactions
• Addition reaction is the reaction in which elements
are added to the starting material.
( X and Y add to two different atoms in a molecule
that has one or more  bonds)

• In an addition reaction, new groups X

and Y are added to the starting material.
A  bond is broken and two  bonds are
formed.
syn and anti addition Y
syn
Z
Y-Z

anti
Y Z
 Bromine addition - an anti addition
+ + Br
Br Br
2. C C -
+ Br C C
1. Br Br Br- + C C
Br

bromonium ion

Br-Br H Br
H
H +
CH3 H CH3
CH3 CH3
cis-but-2-ene

Br Br Br H
H H
+ +
(S,S) H Br (R,R)
H H H Br
Br- H
Br Br-
 Bond Making and Bond Breaking
• A reaction mechanism is a detailed description of how bonds are broken
and formed as starting material is converted into product.

• A reaction can occur either in one step or a series of steps.

Changes in Bonding During a Chemical Reaction
• Regardless of how many steps there are in a reaction, there are only two ways to break (cleave) a bond:
the electrons in the bond can be divided equally or unequally between the two atoms of the bond.

• To illustrate the movement of a single electron, use a half-headed curved arrow, sometimes called a
fishhook.
• A full headed curved arrow shows the movement of an electron pair.

• Homolysis and Heterolysis require energy.

• Homolysis generates uncharged reactive intermediates with unpaired electrons.
• Heterolysis generates charged intermediates.
Using Arrows in Equations and Reaction Mechanisms
Bond breaking forms particles called reactive intermediates.

Three major reactive intermediates resulting from

homolysis and heterolysis of a C – Z bond
Common Reaction Intermediates formed by Breaking a Covalent Bond

Carbon Reactive Intermediates

Carbocation Structure and Stability • Carbon has 6 electrons, positively charged.
• Carbon is sp2 hybridized with vacant p orbital.

• Stabilized by alkyl substituents in two ways:

1. Inductive effect: Donation of electron
density along the sigma bonds.
2. Hyperconjugation: Overlap of sigma
bonding orbitals with empty p orbital.
 Free Radicals

• Also electron-deficient.
• Stabilized by alkyl substituents.
• Order of stability:
3 > 2 > 1 > methyl
 Carbanions

❖ Eight electrons on carbon: 6 bonding plus one lone pair.

❖ Carbon has a negative charge.
❖ Destabilized by alkyl substituents. Methyl >1 > 2  > 3


Carbenes
❑ Carbon is neutral.
❑ Vacant p orbital, so can be electrophilic.
❑ Lone pair of electrons, so can be nucleophilic.
Understanding Organic Reactions Bond Making and Bond Breaking
• Bond formation occurs in two different ways.
• Two radicals can each donate one electron to form a two-electron bond.
• Alternatively, two ions with unlike charges can come together, with the negatively charged ion
donating both electrons to form the resulting two-electron bond.
• Bond formation always releases energy.

• Homolysis generates two uncharged species with unpaired electrons.

• A reactive intermediate with a single unpaired electron is called a radical.
• Radicals are highly unstable because they contain an atom that does not have an octet of electrons.
• Heterolysis generates a carbocation or a carbanion.
• Both carbocations and carbanions are unstable intermediates.
• A carbocation contains a carbon surrounded by only six electrons, and
• A carbanion has a negative charge on carbon, which is not a very electronegative atom.

130
Thermodynamics and Bonding
Bond Making
Bond Dissociation Energy

• The energy absorbed or

released in any reaction,
symbolized by H0, is called
the enthalpy change or heat of
reaction.
• Because bond breaking requires energy, bond
dissociation energies are always positive numbers, and
homolysis is always endothermic.

• Conversely, bond formation always releases energy,

and thus is always exothermic. For example, the H—H
bond requires +104 kcal/mol to cleave and releases –
104 kcal/mol when formed.

Stronger bonds have a higher ΔHº

• Comparing bond dissociation energies is
equivalent to comparing bond strength.
• The stronger the bond, the higher its bond
dissociation energy.
• Bond dissociation energies decrease down
a column of the periodic table.
• Generally, shorter bonds are stronger
bonds.
• Bond dissociation energies are used to calculate the enthalpy change (H0) in a
reaction in which several bonds are broken and formed.
 Bond dissociation energies have some important limitations.
• Bond dissociation energies present overall energy changes only. They reveal nothing about the reaction
mechanism or how fast a reaction proceeds.
• Bond dissociation energies are determined for reactions in the gas phase, whereas most organic reactions
occur in a liquid solvent where solvation energy contributes to the overall enthalpy of a reaction.
• Bond dissociation energies are imperfect indicators of energy changes in a reaction. However, using bond
dissociation energies to calculate H° gives a useful approximation of the energy changes that occur when
bonds are broken and formed in a reaction.
• For a reaction to be practical, the equilibrium must favor products and the reaction rate must be fast
enough to form them in a reasonable time. These two conditions depend on thermodynamics and kinetics
respectively.
• Thermodynamics describes how the energies of reactants and products compare, and what the relative
amounts of reactants and products are at equilibrium.
• Kinetics describes reaction rates.
• The equilibrium constant, Keq, is a mathematical expression that relates the amount of starting material and
product at equilibrium. Thermodynamics and Bonding
• The size of Keq expresses whether the starting materials or products predominate once equilibrium is reached.
• When Keq > 1, equilibrium favors the products (C & D) and the equilibrium lies to the right as the equation is
written.
• When Keq < 1, equilibrium favors the starting materials (A and B) and the equilibrium lies to the left as the
equation is written.
• For a reaction to be useful, the equilibrium must favor the products, and Keq > 1.
• The position of the equilibrium is determined by the relative energies of the reactants and products.
• G° is the overall energy difference between reactants and products.
 •G° is the overall energy difference
between reactants and products.

Summary of the relationship between ∆G° and Keq

• G° is related to the equilibrium constant Keq by the following

equation:
 • When Keq > 1, log Keq is positive, making G° negative, and energy is released. Thus, equilibrium favors
the products when the energy of the products is lower than the energy of the reactants.
• When Keq < 1, log Keq is negative, making G° positive, and energy is absorbed. Thus, equilibrium favors
the reactants when the energy of the products is higher than the energy of the reactants.

• Compounds that are lower in energy

have increased stability.
• The equilibrium favors the products
when they are more stable (lower in
energy) than the starting materials of a
reaction.
• Because G° depends on the
logarithm of Keq, a small change in
energy corresponds to a large
difference in the relative amount of
starting material and product at
equilibrium.
• These equations can be used for any process with two states in equilibrium. As an
example, monosubstituted cyclohexanes exist as two different chair conformations
that rapidly interconvert at room temperature, with the conformation having the
substituent in the roomier equatorial position favored.
• Knowing the energy difference between two conformations permits the calculation of
the amount of each at equilibrium.
Enthalpy and Entropy
• G° depends on H° and the entropy change, S°.
• Entropy change, S°, is a measure of the change in the randomness of a system. The more
disorder present, the higher the entropy. Gas molecules move more freely than liquid molecules
and are higher in entropy. Cyclic molecules have more restricted bond rotation than similar acyclic
molecules and are lower in entropy.
• S° is (+) when the products are more disordered than the reactants. S° is (-) when the products
are less disordered than the reactants.
• Reactions resulting in increased entropy are favored.
• G° is related to H° and S° by the following equation:
 • This equation indicates that the total energy change is due to two factors: the change in bonding energy
and the change in disorder.
• The change in bonding energy can be calculated from bond dissociation energies.
• Entropy changes are important when
The number of molecules of starting material differs from the number of molecules of product in the
balanced chemical equation.
An acyclic molecule is cyclized to a cyclic one, or a cyclic molecule is converted to an acyclic one.

• In most other reactions that are not carried out at high temperature, the entropy term (TS°) is small compared
to the enthalpy term (H0), and therefore it is usually neglected.
 Free Energy Change
▪ G = (energy of products) - (energy of reactants)
▪ G is the amount of energy available to do work.
▪ Negative values indicate spontaneity.

Go = -2.303 RT(log10Keq) where R = 8.314 J/K-mol and T = temperature in kelvins.

Factors Determining G

Free energy change depends on:
• Enthalpy
• H= (enthalpy of products) - (enthalpy of reactants)

• Entropy
• S = (entropy of products) - (entropy of reactants)

G = H - TS

Enthalpy
• Ho = heat released or absorbed during a chemical reaction at standard
conditions.
• Exothermic (-H) heat is released.
• Endothermic (+H) heat is absorbed.
• Reactions favor products with lowest enthalpy (strongest bonds).

Entropy
• So = change in randomness, disorder, or freedom of movement.
• Increasing heat, volume, or number of particles increases entropy.
• Spontaneous reactions maximize disorder and minimize enthalpy.
• In the equation Go = Ho - TSo the entropy value is often small.

Energy Diagrams
• For the general reaction:
• The energy diagram would be shown as:
• An energy diagram is a schematic representation of
the energy changes that take place as reactants are
converted to products.
• An energy diagram plots the energy on the y axis
versus the progress of reaction, often labeled as the
reaction coordinate, on the x axis.
• The energy difference between reactants and products
is H°. If the products are lower in energy than the
reactants, the reaction is exothermic and energy is
released. If the products are higher in energy than the
reactants, the reaction is endothermic and energy is
consumed.
• The unstable energy maximum as a chemical reaction
proceeds from reactants to products is called the
transition state. The transition state species can never
be isolated.
• The energy difference between the transition state and
the starting material is called the energy of activation,
Ea.
• The energy of activation is the minimum amount of energy needed to break the bonds in
the reactants.
• The larger the Ea, the greater the amount of energy that is needed to break bonds, and
the slower the reaction rate.
• The structure of the transition state is somewhere between the structures of the starting
material and product. Any bond that is partially formed or broken is drawn with a dashed
line. Any atom that gains or loses a charge contains a partial charge in the transition
state.
• Transition states are drawn in brackets, with a superscript double dagger (‡).
Some representative energy diagrams
 Comparing ∆H° and Ea in two energy
diagrams

• Consider the following two step reaction:

• An energy diagram must be drawn
for each step.
• The two energy diagrams must
then be combined to form an
energy diagram for the overall
two-step reaction.
• Each step has its own energy
barrier, with a transition state at
the energy maximum.
Complete energy diagram for
the two-step conversion of
Kinetics
• Kinetics is the study of reaction rates.
• Rate of the reaction is a measure of how the
concentration of the products increase while the
concentration of the products decrease.
• A rate equation is also called the rate law and it gives
the relationship between the concentration of the
reactants and the reaction rate observed.
• Rate law is experimentally determined.
• Ea is the energy barrier that must be exceeded for
reactants to be converted to products.
Rate Law • For the reaction A + B → C + D,
rate = kr[A]a[B]b
• a is the order with respect to A
• b is the order with respect to B
• a + b is the overall order

• Order is the number of molecules of that reactant which is present in the rate determining
step of the mechanism.
 Kinetics
• The higher the concentration, the faster the rate.
• The higher the temperature, the faster the rate.
• G°, H°, and Keq do not determine the rate of a reaction. These quantities indicate the direction of
the equilibrium and the relative energy of reactants and products.
• A rate law or rate equation shows the relationship between the reaction rate and the concentration
of the reactants. It is experimentally determined.

• Fast reactions have large rate constants.

• Slow reactions have small rate constants.
• The rate constant k and the energy of activation Ea are inversely related. A high Ea corresponds to a small
k.
• A rate equation contains concentration terms for all reactants in a one-step mechanism.
• A rate equation contains concentration terms for only the reactants involved in the rate-determining step in
a multi-step reaction.
• The order of a rate equation equals the sum of the exponents of the concentration terms in the rate
equation.
• A two-step reaction has a slow rate-determining step, and a fast step.
• In a multi-step mechanism, the reaction can occur no faster than its rate-determining step.
• Only the concentration of the reactants in the rate-determining step appears in the rate equation.
 Catalysts
• Some reactions do not proceed at a reasonable rate unless a catalyst is added.
• A catalyst is a substance that speeds up the rate of a reaction. It is recovered unchanged in
a reaction, and it does not appear in the product.
• Changes the speed of a reaction
• Changes the speed of a reaction: A catalyst is a substance that speeds up the rate of a reaction.
• Does not appear in the product: It is recovered unchanged in a reaction, and it does not appear in
the product
• Many types of catalyst can easily be recovered and used again