Organic Chemistry

Assoc. Prof. Dr. Miyase Gözde Gündüz

Faculty of Pharmacy
Department of Pharmaceutical Chemistry

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Books
 Organic Chemistry, David Klein
 Organic Chemistry, Paula Yurkanis Bruice
 Organic Chemistry with Biological Applications,
John McMurry
 Organic Chemistry, Graham Solomons-Craig
Fryhle-Scott Snyder

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Introduction to Organic Chemistry

In the early nineteenth century, scientists classified

all known compounds into two categories:

Organic compounds were derived from living

organisms (plants and animals),

Inorganic compounds were derived from

nonliving sources (minerals and gases).
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Vitalism was dealt a serious blow in 1828 when
German chemist Friedrich Wöhler demonstrated
the conversion of ammonium cyanate (a known
inorganic salt) into urea, a known organic
compound found in urine:

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For the first time, an “organic” compound had
been obtained from something other than a living
organism and certainly without the aid of any
kind of vital force.
Chemists, therefore, needed a new definition for
“organic compounds.”
Organic compounds are now defined as
compounds that contain carbon.

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Organic chemistry occupies a central role in the
world around us, as we are surrounded by organic
compounds.
Pharmaceuticals, pesticides, paints, adhesives, and
plastics are all made from organic compounds.

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Our bodies are constructed mostly from organic
compounds (DNA, RNA, proteins, etc.) whose
behavior and function are determined by the
guiding principles of organic chemistry.

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The responses of our bodies to pharmaceuticals are
the results of reactions guided by the principles of
organic chemistry. A deep understanding of those
principles enables the design of new drugs that fight
disease and improve the overall quality of life and
longevity. Accordingly, it is not surprising that
organic chemistry is required knowledge for anyone
entering the health professions.

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Atomic Structure
The compounds we encounter in chemistry are made up
of atoms combined in different proportions.
An atom consists of a dense, positively charged nucleus
containing protons and neutrons and a surrounding
cloud of electrons.

Each proton of the nucleus bears one positive charge;

electrons bear one negative charge. Neutrons are
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electrically neutral; they bear no charge.

A specific atom is described by its atomic number (Z),
which gives the number of protons (and electrons) it
contains, and its mass number (A), which gives the total
number of protons plus neutrons in its nucleus.

Atoms with the same atomic number but different

mass numbers are called isotopes.

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Atomic Structure: Orbitals
How are the electrons distributed in an atom?

In three-dimensional space, the orbital describes

the volume of space around a nucleus that an
electron is most likely to occupy.

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What do orbitals look like?
There are four different kinds of orbitals, denoted s, p,
d, and f, each with a different shape. Of the four, we’ll
be concerned primarily with s and p orbitals because
these are the most common in organic and biological
chemistry.

Representations of s, p, and d orbitals. An s orbital is

spherical, a p orbital is dumbbell shaped, and four of
the five d orbitals are cloverleaf-shaped.
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The orbitals in an atom are organized into different
layers, or electron shells. Different shells contain
different numbers and kinds of orbitals, and each
orbital within a shell can be occupied by two
electrons.

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The lowest-energy
arrangement, or ground-state
electron configuration, of an
atom is a listing of the orbitals
occupied by its electrons. We
can predict this arrangement
by following three rules:

1. Aufbau principle: Orbitals

are filled so that those of
lowest energy are filled first.

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2. Pauli exclusion principle: Electrons act in
some ways as if they were spinning around an
axis. This spin can have two orientations,
denoted as up and down . Only two electrons
can occupy an orbital, and they must be of
opposite spin

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3. Hund’s rule: If two or more empty orbitals of
equal energy are available, one electron occupies
each with spins parallel until all orbitals are half-full.

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Development of Chemical Bonding Theory
In 1858, August Kekulé proposed that, in all its
compounds, carbon is tetravalent—it always forms four
bonds when it joins other elements to form stable
compounds.
Shortly after the tetravalent nature of carbon was
proposed, multiple bonding between atoms was
suggested. Emil Erlenmeyer proposed a carbon–carbon
triple bond for acetylene, and Alexander Crum Brown
proposed a carbon– carbon double bond for ethylene.

H2C=CH2
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In 1865, Kekulé provided another major advance
when he suggested that carbon chains can double
back on themselves to form rings of atoms.

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In 1874, Jacobus van’t Hoff and Joseph Le Bel added a
third dimension to our ideas about organic compounds.
They proposed that the four bonds of carbon are not
oriented randomly but have specific spatial directions.
Van’t Hoff went even further and suggested that the four
atoms to which carbon is bonded sit at the corners of a
regular tetrahedron, with carbon in the center.

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Why do atoms bond together?
Atoms bond together because the compound that results
is more stable and lower in energy than the separate
atoms.
How can bonds be described electronically?
We know that eight electrons (an electron octet) in an
atom’s outermost shell, or valence shell, impart special
stability to the noble gas elements in group 8A of the
periodic table

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According to Lewis’s theory, an atom will give up,
accept, or share electrons in order to achieve a filled
outer shell or an outer shell that contains eight
electrons. This theory is called the octet rule.

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The alkali metals in group 1A, for example, achieve a
noble-gas configuration by losing the single s electron
from their valence shell to form a cation, while the
halogens in group 7A achieve a noble-gas
configuration by gaining a p electron to fill their
valence shell and form an anion. The resultant ions are
held together in compounds like NaCl (table salt) by
an electrostatic attraction that we call an ionic bond.

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A bond is an attractive force between two ions or between
two atoms. Attractive forces between opposite charges are
called electrostatic attractions. A bond formed as a result
of the electrostatic attraction between ions of opposite charge
is called an ionic bond .
Sodium chloride is an example of an ionic compound. Ionic
compounds are formed when an element on the left side of
the periodic table transfers one or more electrons to an
element on the right side of the periodic table.

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How do elements closer to the middle of the
periodic table form bonds?
The bonding in methane (CH4) is not ionic because it
would take too much energy for carbon (1s22s22p2) to
either gain or lose four electrons to achieve a noble-
gas configuration.
As a result, carbon bonds to other atoms, not by
gaining or losing electrons, but by sharing them. Such
a shared-electron bond, first proposed in 1916 by G.
N. Lewis, is called a covalent bond.

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A simple way of indicating the covalent bonds in
molecules is to use what are called Lewis structures, or
electron-dot structures, in which the valence shell
electrons of an atom are represented as dots. Thus,
hydrogen has one dot representing its 1s electron,
carbon has four dots (2s22p2), oxygen has six dots (2s2
2p4), and so on.
A stable molecule results whenever a noble-gas
configuration is achieved for all the atoms—eight dots
(an octet) for main-group atoms or two dots for
hydrogen.

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Simpler still is the use of Kekulé structures, or
linebond structures, in which a two-electron
covalent bond is indicated as a line drawn between
atoms.

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The number of covalent bonds an atom forms depends on
how many additional valence electrons it needs to reach a
noble-gas configuration.
Hydrogen has one valence electron (1s) and needs one more
to reach the helium configuration (1s2), so it forms one
bond.
Carbon has four valence electrons (2s22p2) and needs four
more to reach the neon configuration (2s22p6), so it forms
four bonds.
Nitrogen has five valence electrons (2s22p3), needs three
more, and forms three bonds; oxygen has six valence
electrons (2s22p4), needs two more, and forms two bonds;
and the halogens have seven valence electrons, need one
more, and form one bond.
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Valence electrons that are not used for bonding are
called lone-pair electrons, or nonbonding electrons.
The nitrogen atom in ammonia (NH3), for instance,
shares six valence electrons in three covalent bonds
and has its remaining two valence electrons in a
nonbonding lone pair. Nonbonding electrons are often
omitted when drawing line-bond structures, but
they’re often crucial in chemical reactions.

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sp3 Hybrid Orbitals and the Structure of
Methane
Carbon has four valence electrons (2s22p2) and forms
four bonds. Because carbon uses two kinds of orbitals
for bonding, 2s and 2p, we might expect methane to
have two kinds of C–H bonds. In fact, all four C–H
bonds in methane are identical and are spatially
oriented toward the corners of a regular tetrahedron.

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In 1931 Linus Pauling showed mathematically how an
s orbital and three p orbitals on an atom can combine,
or hybridize, to form four equivalent atomic orbitals
with tetrahedral orientation.
These tetrahedrally oriented orbitals are called sp3
hybrids. Superscript 3 in the name sp3 tells how many
of each type of atomic orbital combine to form the
hybrid, not how many electrons occupy it.

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The four C-H bonds are identical because carbon uses
hybrid atomic orbitals.
Hybrid orbitals are mixed orbitals that result from
combining atomic orbitals.

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sp3 Hybrid Orbitals and the Structure of Ethane

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sp2 Hybrid Orbitals and the Structure of Ethylene

Each of the carbon atoms in ethene (also called

ethylene) forms four bonds, but each carbon is bonded
to only three atoms:

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To bond to three atoms, each carbon hybridizes three
atomic orbitals: an s orbital and two of the p orbitals.
Because three orbitals are hybridized, three hybrid orbitals
are formed. These are called sp2 orbitals. After
hybridization, each carbon atom has three degenerate sp2
orbitals and one unhybridized p orbital:

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Three sp2 hybrid orbitals
result, and one 2p orbital
remains unchanged. The
three sp2 orbitals lie in a
plane at angles of 120° to
one another, with the
remaining p orbital
perpendicular to the sp2
plane.
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When two sp2-hybridized carbons approach each other,
they form a bond by sp2–sp2 overlap. At the same time,
the unhybridized p orbitals approach with the correct
geometry for sideways overlap, leading to the formation
of what is called a pi (π) bond.

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sp Hybrid Orbitals and the Structure of Acetylene

The two unhybridized p orbitals

are perpendicular to each other
and are perpendicular to the sp
orbitals
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The Bonds in Ammonia and Water
The nitrogen atom in ammonia (NH3) forms three covalent
bonds. Nitrogen’s electronic configuration shows that it
has three unpaired valence electrons , so it does not need to
promote an electron to form the three covalent bonds
required to achieve an outer shell of eight electrons to
complete its octet.

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The oxygen atom in water (H2O) forms two covalent
bonds. Because oxygen’s electronic configuration shows
that it has two unpaired valence electrons, oxygen does
not need to promote an electron to form the two covalent
bonds required to complete its octet.

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Hybridization, Bond Lengths, Bond Strengths,
and Bond Angles

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Carbon–carbon bond gets
shorter and stronger as the
number of bonds holding the
two carbon atoms together
increases.

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The length and strength of a C-H bond both depend on the
hybridization of the carbon to which the hydrogen is attached.
The more s character in the orbital used by carbon to form the
bond, the shorter and stronger is the bond—again because an
s orbital is closer to the nucleus than is a p orbital.

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Drawing Chemical Structures
A line between atoms represent the two electrons in a
covalent bond.
In condensed structures, carbon–hydrogen and
carbon– carbon single bonds aren’t shown

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Polar Covalent Bonds-Acids and Bases
Up to this point, we’ve treated chemical bonds as either
ionic or covalent. Most bonds, however, are neither fully
ionic nor fully covalent but are somewhere between the two
extremes. Such bonds are called polar covalent bonds,
meaning that the bonding electrons are attracted more
strongly by one atom than the other so that the electron
distribution between atoms is not symmetrical.

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Bond polarity is due to differences in electronegativity
(EN), the intrinsic ability of an atom to attract the shared
electrons in a covalent bond.

Metals on the left side of the periodic table attract electrons

weakly and have lower electronegativities, while oxygen,
nitrogen, and halogens on the right side of the periodic
table attract electrons strongly and have higher electro-
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negativities.
 An inductive effect is
simply the shifting of
electrons in a σ bond in
response to the
electronegativity of
nearby atoms. Metals,
such as lithium and
magnesium, inductively
donate electrons,
whereas reactive non-
metals, such as oxygen
and nitrogen,
inductively withdraw
electrons.
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 Formal Charges
Concept of assigning formal charges to specific atoms
within a molecule, particularly atoms that have an
apparently “abnormal” number of bonds.

How to calculate formal charge?

First, we determine how many valence electrons an atom
would have if it were an atom not bonded to any other
atoms. This is equal to the group number of the atom in
the periodic table. For hydrogen this number equals 1, for
carbon it equals 4, for nitrogen it equals 5, and for oxygen it
equals 6.

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Next, we examine the atom in the lewis structure and we
assign the valence electrons in the following way:
We assign to each atom half of the electrons it is sharing
with another atom and all of its unshared (lone) electron
pairs.
Then we do the following calculation for the atom:

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 Acids and Bases:

There are two frequently used definitions of

acidity:
- The Brønsted–Lowry definition and
- The Lewis definition.

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Brønsted–Lowry acid is a substance that donates a proton
(H), and
Brønsted–Lowry base is a substance that accepts a
proton.

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Acid and Base Strength
Acids differ in their ability to donate H. Stronger acids,
such as HCl, react almost completely with water,
whereas weaker acids, such as acetic acid (CH3CO2H),
react only slightly.
The exact strength of a given acid HA in water solution
is described using the acidity constant (Ka) for the
acid-dissociation equilibrium.

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Acid strengths are normally expressed using pKa
values rather than Ka values, where the pKa is the
negative common logarithm of the Ka:

A stronger acid (larger Ka) has a smaller pKa, and a

weaker acid (smaller Ka) has a larger pKa.

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A strong acid is one that loses an H easily, meaning that its
conjugate base holds on to the H weakly and is therefore a weak
base. A weak acid is one that loses an H with difficulty, meaning
that its conjugate base holds on to the H strongly and is therefore
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a strong base.
How the Structure of an Acid Affects Its pKa Value

Electronegativity

The strongest acid has its hydrogen attached to the

most electronegative atom

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Because the more electronegative the atom, the better
it can bear its negative charge. Thus, the strongest acid
has the most stable (weakest) conjugate base .

The effect that the electronegativity of the atom bonded to a

hydrogen has on the compound’s acidity can be appreciated
when the pKa values of alcohols and amines are compared.
Because oxygen is more electronegative than nitrogen, an
alcohol is more acidic than an amine.

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Hybridization
The hybridization of an atom affects the acidity of a
hydrogen bonded to it because hybridization affects
electronegativity:

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 Why does the hybridization of the atom affect its
electronegativity?
Electronegativity is a measure of the ability of
an atom to pull the bonding electrons toward
itself. Thus, the most electronegative atom
will be the one with its bonding electrons
closest to the nucleus. The average distance of
a 2s electron from the nucleus is less than the
average distance of a 2p electron from the
nucleus. Therefore, an sp hybridized atom
with 50% s character is the most
electronegative, an sp2 hybridized atom
(33.3% s character) is next, and an sp3
hybridized atom (25% s character) is the least
electronegative. 72
How Substituents Affect the Strength of an Acid
Although the acidic proton of each of the following
carboxylic acids is attached to the same atom (an oxygen),
the four compounds have different pK a values:

The halogen is more electronegative than the hydrogen it

has replaced, so the halogen pulls the bonding electrons
toward itself more than a hydrogen would.
Pulling electrons through sigma bonds is called inductive
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electron withdrawal.
If we look at the conjugate base of a carboxylic acid, we
see that inductive electron withdrawal decreases the
electron density about the oxygen that bears the negative
charge, thereby stabilizing it. And we know that stabilizing
a base increases the acidity of its conjugate acid.

The pKa values of the four carboxylic acids (become more

acidic) as the electron-withdrawing ability
(electronegativity) of the halogen increases.
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The effect a substituent has on the acidity of a
compound decreases as the distance between the
substituent and the acidic proton increases.

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Delocalized Electrons
Carboxylic acid has a pKa value of about 5, whereas
the pKa value of an alcohol is about 15. Because a
carboxylic acid is a much stronger acid than an
alcohol, the conjugate base of a carboxylic acid is
considerably more stable than the conjugate base of
an alcohol.

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Two factors cause the conjugate base of a carboxylic
acid to be more stable than the conjugate base of an
alcohol.

Inductive electron withdrawal by electronegative

oxygen decreases the electron density of the negatively
charged oxygen, thereby stabilizing it and increasing
the acidity of the conjugate acid.
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The second factor that causes the conjugate base of the
carboxylic acid to be more stable than the conjugate base
of the alcohol is electron delocalization . When an alcohol
loses a proton, the negative charge resides on its single
oxygen atom. These electrons are said to be localized
because they belong to only one atom. In contrast, when a
carboxylic acid loses a proton, the negative charge is
shared by both oxygens. These electrons are delocalized .

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The two structures shown for the conjugate base of the
carboxylic acid are called resonance contributors.

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Lewis Acids and Bases
The Lewis definition of acids and bases is broader and
more encompassing than the Brønsted–Lowry definition
because it’s not limited to substances that donate or accept
protons.
A Lewis acid is a substance that accepts an electron pair,
and
A Lewis base is a substance that donates an electron pair.

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Lewis Acids
The fact that a Lewis acid is able to accept an electron pair
means that it must have either a vacant, low-energy orbital
or a polar bond to hydrogen so that it can donate H+. Thus,
the Lewis definition of acidity includes many species in
addition to H +.

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Compounds of group 3A elements, such as BF3 and
AlCl3, are Lewis acids because they have unfilled
valence orbitals and can accept electron pairs from
Lewis bases

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Lewis Bases
The Lewis definition of a base—a compound with a pair
of nonbonding electrons that it can use in bonding to a
Lewis acid.

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In a more general sense, most oxygen- and nitrogen-
containing organic compounds can act as Lewis bases
because they have lone pairs of electrons.

Alcohols and carboxylic acids, for instance, act as acids

when they donate an H + but as bases when their oxygen
atom accepts an H +.

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Noncovalent Interactions between Molecules
When thinking about chemical reactivity, chemists
usually focus on the covalent interactions between atoms
within individual molecules. Also important, however,
particularly in large biomolecules like proteins and
nucleic acids, are a variety of interactions between
molecules that strongly affect molecular properties.
Collectively called either intermolecular forces, van der
Waals forces, or noncovalent interactions, they are of
several different types: dipole–dipole forces, dispersion
forces, and hydrogen bonds.
Van der Waals forces: Intermolecular forces that are
responsible for holding molecules together in the liquid
and solid states. 87
We will focus our attention on three types:

1. Dipole–dipole forces
2. Dispersion forces
3. Hydrogen bonds

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Dipole–dipole forces occur between polar molecules as a
result of electrostatic interactions among dipoles. The
forces can be either attractive or repulsive depending on
the orientation of the molecules—attractive when unlike
charges are together and repulsive when like charges are
together.

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Ion–dipole force: The interaction of an ion with a
permanent dipole. Such interactions (resulting in
solvation) occur between ions and the molecules of
polar solvents.

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Dispersion forces occur between all neighboring
molecules and arise because the electron distribution
within molecules is constantly changing.
Although uniform on a time-averaged basis, the electron
distribution even in nonpolar molecules is likely to be
nonuniform at any given instant. One side of a molecule
may, by chance, have a slight excess of electrons relative to
the opposite side, giving the molecule a temporary dipole.
Attractive dispersion
forces in nonpolar
molecules are caused
by temporary dipoles,
as shown in these
models of pentane,
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C5H12.
Hydrogen bond is an attractive interaction between a
hydrogen bonded to an electronegative O or N atom
and an unshared electron pair on another O or N
atom.

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Hydrogen-bonding has enormous consequences for living
organisms. Hydrogen bonds cause water to be a liquid rather
than a gas at ordinary temperatures, they hold enzymes in
the shapes necessary for catalyzing biological reactions, and
they cause strands of deoxyribonucleic acid (DNA) to pair
up and coil into the double helix that stores genetic
information.

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Hydrophilic, meaning “water-loving,” to describe a
substance that is strongly attracted to water and the
term hydrophobic, meaning “water-fearing,” to
describe a substance that is not strongly attracted to
water.

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Hydrophilic substances, such as table sugar, usually
have a number of ionic charges or polar –OH groups in
their structure so they can form hydrogen bonds,
whereas hydrophobic substances, such as vegetable oil,
do not have groups that form hydrogen bonds, so their
attraction to water is limited to weak dispersion forces

Ethanol and water

are miscible in all
proportions

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An overview of organic reactions
There are four general types of organic reactions:
 additions,
 eliminations,
 substitutions, and
 rearrangements.

Reactant: Starting materials in chemical reactions

Product: Substances formed during chemical reaction

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Addition reactions occur when two reactants add
together to form a single product with no atoms “left
over.”

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Elimination reactions are, in a sense, the opposite of
addition reactions. They occur when a single reactant
splits into two products, often with formation of a small
molecule such as water.

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Substitution reactions occur when two reactants
exchange parts to give two new products.

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Rearrangement reactions occur when a single
reactant undergoes a reorganization of bonds and atoms
to yield a structural isomeric product.

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How Organic Reactions Occur: Mechanisms
An overall description of how a reaction occurs is called
a reaction mechanism.
A mechanism describes in detail exactly what takes
place at each stage of a chemical transformation—which
bonds are broken and in what order, which bonds are
formed and in what order, and what the relative rates of
the steps are.

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Molecules come together, react, and yield products,
specific bonds in the reactant molecules are broken
and specific bonds in the product molecules are
formed. Fundamentally, there are two ways in which a
covalent two electron bond can break:
-A bond can break in an electronically symmetrical
way so that one electron remains with each product
fragment, or
-A bond can break in an electronically unsymmetrical
way so that both bonding electrons remain with one
product fragment, leaving the other with a vacant
orbital.
The symmetrical cleavage is said to be homolytic, and
the unsymmetrical cleavage is said to be heterolytic.
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Half-headed
curved arrow

Full-headed
curved arrow

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Radical Reactions
Radical reactions are not as common as polar reactions but
are nevertheless important in some industrial processes and
in numerous biological pathways. A radical is highly
reactive because it contains an atom with an odd number of
electrons (usually seven) in its valence shell rather than a
stable, noble gas octet.

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As a biological example of radical reactions, look at the
synthesis of prostaglandins, a large class of molecules found in
virtually all body tissues and fluids.
A number of pharmaceuticals are based on or derived from
prostaglandins, including medicines that reduce intraocular
pressure in glaucoma, control bronchial asthma, and help treat
congenital heart defects.

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Polar Reactions
Polar reactions occur because of the electrical attraction
between positively polarized and negatively polarized
centers on functional groups in molecules.

Bond polarity is a consequence of an unsymmetrical

electron distribution in a bond and is due to the difference
in electronegativity of the bonded atoms.

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Elements such as oxygen, nitrogen, fluorine, and chlorine
are more electronegative than carbon, so a carbon atom
bonded to one of these atoms has a partial positive charge
(δ+). Conversely, metals are less electronegative than
carbon, so a carbon atom bonded to a metal has a partial
negative charge (δ-).

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Polarity Patterns in Some Common Functional
Groups

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Polar bonds can also result from the interaction of
functional groups with acids or bases.

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In referring to the electron-rich and electron-poor
species involved in polar reactions, chemists use the
words nucleophile and electrophile.

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A nucleophile is a substance that is “nucleus-loving.”
(Remember that a nucleus is positively charged.) A
nucleophile has a negatively polarized, electron-rich atom
and can form a bond by donating a pair of electrons to a
positively polarized, electron-poor atom. Nucleophiles can
be either neutral or negatively charged.

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An electrophile, by contrast, is “electron-loving.” An
electrophile has a positively polarized, electron-poor
atom and can form a bond by accepting a pair of
electrons from a nucleophile. Electrophiles can be either
neutral or positively charged.

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An Example of a Polar Reaction: Addition of H2O to
Ethylene

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Carbocation and Carbanion
Heterolysis of a bond to a carbon atom can lead to
either of two ions: either to an ion with a positive
charge on the carbon atom, called a carbocation, or to
an ion with a negatively charged carbon atom, called a
carbanion:

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Why are more highly substituted carbocations more
stable than less highly substituted ones? There are two
reasons:
-Inductive effect The more alkyl groups there are
attached to the positively charged carbon, the more
electron density shifts toward the charge and the more
inductive stabilization of the cation occurs.
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The more alkyl groups there are bonded to the positively
charged carbon, the more electron density shifts toward
the charge making the charged carbon less electron poor
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-Hyperconjugation
Hyperconjugation is the stabilising interaction that results
from the interaction of the electrons in a σ-bond (usually
C-H or C-C) with an adjacent empty or partially filled p-
orbital or a π-orbital to give an extended molecular orbital
that increases the stability of the system.

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In the ethyl carbocation, CH3CH2+, there is a stabilizing
interaction between the carbocation p orbital and adjacent
C–H bonds on the methyl substituent, as indicated by this
molecular orbital. The more substituents there are, the
greater the stabilization of the cation. Only the C–H bonds
that are roughly parallel to the neighboring p orbital are
oriented properly to take part in hyperconjugation.
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How an adjacent sigma bond helps
stabilize the positive charge of a
carbocation. Electron density from
one of the carbon–hydrogen sigma
bonds of the methyl group flows into
the vacant p orbital of the carbocation
because the orbitals can partly
overlap. Shifting electron density in
this way makes the sp2-hybridized
carbon of the carbocation somewhat
less positive, and the hydrogens of
the methyl group assume some of the
positive charge.
Delocalization (dispersal) of the
charge in this way leads to greater
stability. This interaction of a bond
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orbital with a p orbital is called

Tertiary carbocations have three carbons with C-H bonds
adjacent to the carbocation that can overlap partially with
the vacant p orbital. Secondary carbocations have only two
adjacent carbons with C-H or C-C bonds to overlap with
the carbocation; hence, the possibility for hyperconjugation
is less and the secondary carbocation is less stable. A
methyl carbocation has no possibility for
hyperconjugation, and it is the least stable of all in this
series.

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Curved Arrows in Polar Reaction Mechanisms
Electrons move from a nucleophilic source (Nu: or
Nu:-) to an electrophilic center (E or E+).

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The nucleophile can be either negatively charged or
neutral.

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The electrophile can be either positively charged or
neutral.

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Isomers

Isomers are different compounds that have the same

molecular formula.

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Constitutional isomers have the same molecular
formula but different connectivity, meaning that their
atoms are connected in a different order.

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Stereoisomers

Stereoisomers are not constitutional isomers.

Stereoisomers have their atoms connected in the same
sequence (the same constitution), but they differ in the
arrangement of their atoms in space.
The consideration of such spatial aspects of molecular
structure is called stereochemistry.

130
Stereoisomers and Conformational Stereoisomers

Stereoisomers have the same molecular formula and

connectivity but different arrangements of atoms in
three-dimensional space.

Conformational stereoisomers are related to one another

by bond rotations.

We shall see that there are other types of stereoisomers

that cannot be interconverted simply by rotations about
single bonds.

131
Conformations of Cyclohexane: The Chair and The Boat
The most stable conformation of cyclohexane is the chair
conformation.
By partial rotations about the carbon-carbon single bonds of
the ring, the chair conformation can assume another shape
called the boat conformation.

Chair Conformation Boat Conformation

132
In a chair conformation, all of the carbon–carbon bond
angles are 109.50, and are thereby free of angle strain.
When viewed along any carbon–carbon bond, the
hydrogen atoms at opposite corners of the cyclohexane
ring are maximally separated.
133
134
Cis-Trans Isomers
(Geometric Isomers)

cis–trans isomers (also

called geometric
isomers) result from
restricted rotation.
Restricted rotation can
be caused either by a
cyclic structure or by a
double bond.

135
The cis isomer has its substituents on the same side of the
ring; the trans isomer has its substituents on opposite sides
of the ring. (A solid wedge represents a bond that points
out of the plane of the paper toward the viewer and a
hatched wedge represents a bond that points into the plane
of the paper away from the viewer.)

136
Compounds with carbon-carbon double bonds can
also have cis and trans isomers.

The compound with the hydrogens on the same side

of the double bond is called the cis isomer; the
compound with the hydrogens on opposite sides of
the double bond is called the trans isomer.
137
the cis and trans isomers have the same molecular
formula and the same bonds but have different
configurations —they differ in the way their atoms are
oriented in space.
Cis and trans isomers can be separated from each other
because they are different compounds with different
physical properties—for example, they have different
boiling points

138
If one of the sp2 carbons is attached to two identical
substituents, then the compound cannot have cis and
trans isomers.

139
Naming Alkenes Using The E,Z System
The E,Z system of
nomenclature was
devised for alkenes
that do not have a
hydrogen attached to
each of the sp2
carbons.

140
 To name an isomer by the E,Z system, we first determine
the relative priorities of the two groups bonded to one of the
sp2 carbons and then the relative priorities of the two groups
bonded to the other sp2 carbon.

If the two high-priority groups (one from each carbon) are on

the same side of the double bond, the isomer is the Z isomer
(Z is for zusammen, German for “together”). If the high-
priority groups are on opposite sides of the double bond, the
isomer is the E isomer (E is for entgegen, German for
141

“opposite”).
142
143
Chirality

A chiral object is one that cannot be superposed on its

mirror image.

144
Objects are not the only things that can be chiral.
Molecules can be chiral too. The usual cause of
chirality in a molecule is an asymmetric center .

An asymmetric center (also called a chiral center) is

an atom bonded to four different groups.

145
A compound with one asymmetric center, such as 2-
bromobutane, can exist as two stereoisomers.
If we imagine a mirror between the two stereoisomers,
we can see they are mirror images of each other.
Moreover, they are nonsuperimposable mirror images,
which makes them different molecules.

146
Molecules that are nonsuperimposable mirror images
of each other are called enantiomers (from the Greek
enantion , which means “opposite”).

147
A molecule that has a nonsuperimposable mirror
image, like an object that has a nonsuperimposable
mirror image, is chiral. Therefore, each member of a
pair of enantiomers is chiral. A molecule that has a
superimposable mirror image, like an object that has
a superimposable mirror image, is achiral.
148
How to Draw Enantiomers
Chemists draw enantiomers using either perspective
formulas or Fischer projections. A perspective formula
shows two of the bonds to the asymmetric center in the
plane of the paper, one bond as a solid wedge protruding
forward out of the paper, and the fourth bond as a hatched
wedge extending behind the paper.

149
A Fischer projection represents an asymmetric center as the
point of intersection of two perpendicular lines. Horizontal
lines represent the bonds that project out of the plane of the
paper toward the viewer, and vertical lines represent the
bonds that extend back from the plane of the paper away from
the viewer. The carbon chain is usually drawn vertically, with
C-1 at the top.

150
The use of Fischer projections in non-carbohydrates is
discouraged, as such drawings are ambiguous when
confused with other types of drawing.

D-glucose 151
Naming Enantiomers By The R,S System
How do we name the different stereoisomers of a
compound like 2-bromobutane so that we know which one
we are talking about? We need a system of nomenclature
that indicates the arrangement of the atoms or groups
around the asymmetric center. Chemists use the letters R
and S for this purpose.
For any pair of enantiomers
with one asymmetric center,
one member will have the R
configuration and the other
will have the S configuration.
This system of nomenclature
is called the Cahn-Ingold-
Prelog system after the three
152

scientists who devised it.

Rank the groups (or atoms) bonded to the asymmetric center
in order of priority. The atomic numbers of the atoms
directly attached to the asymmetric center determine the
relative priorities. The higher the atomic number of the
atom, the higher the priority.
If there is a tie, you need to consider the atoms to which the
tied atoms are attached.
Therefore, bromine has the highest priority (1), the ethyl
group has the second highest priority (2), the methyl group
has the third highest priority (3), and hydrogen has the
lowest priority (4).

153
When we examine the methyl group, we find that the next
set of atoms bonded to the carbon consists of three
hydrogen atoms (H, H, H). In the ethyl group the next set
of atoms bonded to the carbon consists of one carbon atom
and two hydrogen atoms (C, H, H). Carbon has a higher
atomic number than hydrogen, so we assign the ethyl
group the higher priority than the methyl group since (C,
H,H)> (H, H, H):

154
We now rotate the formula (or
model) so that the group with
lowest priority (4) is directed
away from us:

Draw an arrow from the group (or atom) with the highest
priority (1) to the one with the second highest priority (2),
and then to the one with the third highest priority (3).
If the arrow points clockwise, the compound has the R
configuration ( R is for rectus ,which is Latin for “right”).
If the arrow points counterclockwise, then the compound
has the S configuration ( S is for sinister , which is Latin
for “left”). The letter R or S (in parentheses) precedes the
systematic name of the compound.
155
156
Groups containing double or triple bonds are assigned
priorities as if both atoms were duplicated or triplicated—

Thus, the vinyl group, -CH=CH2, is of higher priority than

the isopropyl group, -CH(CH3)2.

157
Enantiomers share many of the same properties, including the
same boiling points, the same melting points, and the same
solubilities. In fact, all the physical properties of enantiomers
are the same except those that stem from how groups bonded to
the asymmetric center are arranged in space. One property that
enantiomers do not share is the way they interact with plane-
polarized light.
When plane-polarized light passes through a solution of
achiral molecules, the light emerges from the solution with its
plane of polarization unchanged.

158
When plane-polarized light passes through a solution of
chiral molecules, the light emerges with its plane of
polarization rotated either clockwise or counterclockwise.
If one enantiomer rotates it clockwise, its mirror image
will rotate it exactly the same amount counterclockwise.
159
A compound that rotates the plane of polarization of plane-
polarized light is said to be optically active. In other words,
chiral compounds are optically active, and achiral
compounds are optically inactive .
If an optically active compound rotates the plane of
polarization clockwise, then the compound is said to be
dextrorotatory , which can be indicated in the compound’s
name by the prefix ( + ). If it rotates the plane of
polarization counterclockwise, then it is said to be
levorotatory , which can be indicated by ( - ). Dextro and
levo are Latin prefixes for “to the right” and “to the left,”
respectively. Sometimes lowercase d and l are used instead
of ( + ) and ( - ).
Do not confuse ( + ) and ( - ) with R and S!
160
Compounds With More Than One Asymmetric Center
Many organic compounds have more than one
asymmetric center. a compound can have a maximum of
2n stereoisomers, where n equals the number of
asymmetric centers

161
The four stereoisomers of 3-chloro-2-butanol consist of two
pairs of enantiomers.
Stereoisomers 1 and 2 are nonsuperimposable mirror images.
They, therefore, are enantiomers. Stereoisomers 3 and 4 are
also enantiomers. Stereoisomers 1 and 3 are not identical,
and they are not mirror images. Such stereoisomers are called
diastereomers.
Stereoisomers 1 and 4, 2 and 3, and 2 and 4 are also pairs of
162
diastereomers.
163
The Biological Significance of Chirality
The human body is structurally chiral, with the heart lying
to the left of center and the liver to the right.
Most of the molecules of life such as amino acids, DNA
and natural sugars are chiral.
All amino acids except glycine are chiral because they all
contain at least one chiral centre.
The general formula for an amino acid is

164
Most pharmaceuticals are chiral. Usually only one mirror-
image form of a drug provides the desired effect. The other
mirror-image form is often inactive or, at best, less active.
In some cases the other mirror-image form of a drug
actually has severe side effects or toxicity.

For several years before 1963 the drug thalidomide was

used to alleviate the symptoms of morning sickness in
pregnant women. In 1963 it was discovered that
thalidomide was the cause of horrible birth defects in many
children born subsequent to the use of the drug.

165
Even later, evidence began to appear indicating that whereas
one of the thalidomide enantiomers has the intended effect
of curing morning sickness, the other enantiomer, which
was also present in the drug (in an equal amount), may be
the cause of the birth defects.

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