CHEM 3013
ORGANIC CHEMISTRY I
LECTURE NOTES
CHAPTER 5
Introduction
Organic reactions can be organized in two ways: What kind of reaction occurs, and how
the reaction takes place. Initially, it is easier to consider what kinds of reaction occur. There are
four important kinds of organic reactions these are: Addition , Elimination, Substitution and
Rearrangement reactions.
ADDITION REACTIONS
A + B
C
These reactants
add together......
to give a single product
H
+
H
H
H
ELIMINATION REACTIONS
A
B + C
This one
reactant......
splits apart to
form two products.
OH
+
H
OH
H
SUBSTITUTION REACTIONS
A-B + C-D
A-D + C-B
These two reactanst
exchange parts......
to form these two
new products
CH3
Cl
+ NaOH
CH3
OH
+ NaCl
REARRANGEMENT REACTIONS
A
This single reactant......
B
gives this isomeric
product.
O
O
REACTION TYPES
1.
Electrophilic and Nucleophilic Reagents
Reactions usually occur at the reactive sites of molecules and ions. These sites fall mainly
into two categories. One type has high electron density because:(a) the site has an unshared pair of
electrons or (b) is the negatively charged end -∂ of a polar bond or (c) has C=C π electrons. Such
electron rich sites are nucleophilic and the species possessing such sites are called
nucleophiles or electron-donors. The second category (a) is capable of acquiring more
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electrons of (b) is the +∂ end of a polar bond. These electron-deficient sites are electrophilic and
the species possessing such sites are called electrophiles or electron acceptors. Many
organic reactions occur by covalent bond formation between a nucleophilic and an electrophilic
site.
Nu: + E => Nu:E
2.
Organic Reaction 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 reaction. It
describes what bonds are broken and in what order, and also accounts for all reactants used,
products used, and the relative amounts of each. In this course we will be discussing
chemistry in terms of detailed reaction mechanisms . It is essential to understand
how to write and interpret curved-arrow mechanisms. By knowing a finite
number of mechanisms, it is possible to generalize most of organic chemistry.
a. Bond Fission/Formation
All chemical reactions involve bond breaking and bond making. There are two ways in
which a covalent bond between two atoms or molecular fragments can break. A bond can break in
an electrically symmetrical way such that each fragment goes away with one electron of the two
electron covalent bond. This symmetrical cleavage is called a homolytic process. Alternatively,
the bond can break in an unsymmetrical way, with one fragment leaving with two electrons while
the second fragment has none. The unsymmetrical cleavage is called a heterolytic process.
Likewise, bonds can be formed by the inverse of these two processes; these are called homogenic
and heterogenic bond forming processes.
Processes that involve heterolytic bond breaking or heterogenic bond making are called
radical reactions. A radical (sometimes called a free radical) has a single, unpaired electron in one
of its orbitals.
Processes that involve homolytic bond breaking or homogenic bond formation are
described as polar reactions. Polar reactions involve species which have an even number of
electrons, and are often charged, that is they have a positive or negative charge. Most of the
reaction processes in organic chemistry involve polar reactions.
2
3
8 electrons
Heterolytic
H
Br Cleavage
H
+
Br
Bromide
ion
Hydrogen
ion
7 electrons
Homolytic
H
Br Cleavage
H
+
Br
Bromine
radical
Hydrogen
radical
Note the use of the full arrow to indicate heterolytic
cleavage, while the use of the "fishhook", single
barbed arrow indicates the homolytic formation of
radicals.
Heterolytic and Homolytic bond Cleavage
b.
Radical Reactions
Although most radicals are electrically neutral, they are very highly reactive items because
they have an odd number of electrons (usually seven) in their outer shell. Thus they do not have a
stable noble gas configuration. In order to obtain a filled outer shell, radicals behave in two
general ways: 1. Abstraction of an atom from another molecule, leaving behind another radical.
The net result is a radical substitution reaction. or, 2. Addition of a radical to another molecule
Abstraction
Br
+ H
CH3
Reactant
radical
H
Br
Substitution
product
+
H3C
Product
radical
Addition
Br
Br
+ H 2C
Reactant
radical
Radical Reactions
CH2
C CH2
H2
Addition product
radical
Many radical reactions occur via a multistep process known as a Chain Reaction. There are
three basic types of steps in a radical chain reaction. They are:
1. Initiation- the initial production of radicals. The initiation step begins by
homolytically cleaving relatively weak bonds to produce radicals. This step
usually requires energy ( to overcome the covalent bond) in the form of heat or
electromagnetic radiation (such as UV light).
2. Propagation- radicals undergo substitution or addition processes. Once the first
radicals have been produced, they undergo abstraction or addition processes
(depending on the substrate). Both of these reactions lead to other radicals which can
cycle back into the first propagation step, a series of reactions can be repeated over and
over again.
3. Termination- the chain is broken. Occasionally, two radicals may collide and form a
stable product. When this happens, radicals are taken out of circulation, the reaction
cycle is ended and the chain is broken.
c.
Polar Reactions
Polar reactions occur because of interactions between positive and negative charges on
molecules. The reaction between a Lewis acid and Lewis base discussed in Chapter 2 is an
example of a polar reaction. The fundamental characteristic of all polar reactions is that electron
poor sites in the Electrophile react with electron rich sites in the Nucleophile . Bonds are
formed when the Nucleophile donates a pair of electrons to the Electrophile. When bonds are
broken, one of the two product fragments (the more electronegative one), leaves with the electron
pair.
empty orbital
F
F
+
F
B F
F
Boron triflouride
Flouride anion
Lewis acid
Lewis base
NUCLEOPHILE ELECTROPHILE
F
B F
F
Tetrafluoroborate anion
Polar Reaction of Electrophile and Nucleophile
Most organic molecules are electrically neutral, they have no net charge. However, many
bonds are polarized due to an unsymmetrical sharing of electrons in the bond as a result of
differences in electronegativity of the bonded atoms. Elements more electronegative than carbon
(e.g. O, N and halogens) will pull electrons away from carbon resulting in a partial positive (∂+)
charge on it . Whereas elements less electronegative (most metals) will give up their electrons to
carbon resulting in a partial negative charge (∂-) on it. Thus, different elements bonded to carbon
may make it electron rich (i.e., a Nucleophile) or electron poor (i.e., an Electrophile). In
fundamentally polar process involving polar compounds, regions of rich electron density of the
Nucleophile react with regions of low electron density in the Electrophile.
Consider the reaction of methyllithium with formaldehyde. Since oxygen is more
electronegative than carbon, the bond in formaldehyde will be polarized toward the oxygen. This
places a partial positive charge on the carbon of formaldehyde, it is the Electrophile. The methyl
lithium has a partial negative charge on the carbon, it is the nucleophile. The mechanism shows
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that the carbon of methyllithium with its electrons attacks the carbon of formaldehyde with the
negative charge ending up on the oxygen. There is a great deal of symbolic information in the
mechanism.
δ+ Li
δ− CH3
H
H
H
C
δ+
O
δ−
H 3C
C
O
Li+
H
Mechanism of Methyllithium Addition to Formaldehyde
3.
Thermodynamics
Consider the following reaction: HO- + CH 3 Cl ===> CH 3 OH + Cl We can ask ourselves many questions about this reaction. Will the chemical reaction described
above occur? If it does occur, what would be the extent of the reaction? If the reaction does not
occur, is there anything we can do to bring it about ? These questions can be answered if we know
about the energy relationships between the starting materials and reaction products. The branch of
chemistry which describes these energy relationships is known as Thermodynamics .
a.
Extent of Reaction
Consider a large downtown office building. Before 9AM the building is empty, soon
people begin to fill up the building. After a while, the number of new people going into the
building to conduct business is balanced by the number of people leaving the building having
completed their business. The building's population has reached a steady state, it is at equilibrium.
The building's steady state population (how many people are inside) is a function of a variety of
factors.
All chemical reactions are, by definition, reversible. When we initiate a reaction, the
reactants begin to form products. However , the products are also capable of undergoing a
retrograde process to give the reactants. After a while the extent of the forward reaction is balanced
by the extent of reverse reaction. The reaction is said to come to equilibrium. At equilibrium, the
extent of the reaction (i.e., how much product forms and how much reactant is left) is measured by
the Equilibrium Constant, Keq
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6
A + B
Keq
C + D
Keq = concentration of products at equilibrium
concentration of reactants
Keq = [C] [D] where [A] is the concentration of
[A] [B] reactant A in mol/ L at equilibrium
When Keq > 1...Products favored
When Keq < 1...Reactants favored
Consider the equilibrium concentrations of two
isomeric alkenes.
H 3C
H
C
C
CH3
H 3C
H
24%
H
C
C
H
CH3
76%
Keq = [Products] = 76/24 = 3.2
[Reactants]
Equilibrium
The equilibrium constant tells us which side of the reaction arrow is more favored. If Keq
is larger than one, the product concentration is larger than the reactant concentration. The reaction
will proceed from left to right as written. Conversely, if Keq is less than one, the reaction does not
take place as written.
For practical purposes, an equilibrim constant of 103 or larger is considered to be a
complete reaction, since the amount of reactant left over would be 0.1% or less of the original
amount.
What determines the direction and extent of the reaction at equilibrium? For a reaction
to have a favorable K eq (>1) and proceed as written, the products MUST be
lower in energy than the reactants.
b.
Free Energy and Chemical Equilibrium
The total amount of energy change during a reaction is called the Gibbs free energy
change signified by the symbol ∆G˚. By convention, a favorable reaction is one in which
energy is lost by the system and is signified by a negative ∆G˚ value. When ∆G˚ has a
positive value, energy is absorbed by the system.
One of the most important equations is the one which relates free energy
(∆G˚) and the equilibrium constant K eq
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∆G = -RT ln Keq
= -2.303RT log Keq
Temp in K (C + 273)
1.9872 x 10-3 Kcal/degree-mol
Gibb's Free Energy
Keq = 1016 at 25 C
HO + CH3Cl
CH3OH + Cl-
HO- + CH3Cl
-
Reaction proceeds to completion!
∆G = -RT lnKeq
= -(1.986 cal/K-mol x 298 K x ln 1016)
= - 22,000cal/mol = -22 Kcal/mol
E
N
E
R
G
Y
∆G = -22 Kcal/mol
Reaction is
EXOTHERMIC
CH3OH + Cl-
Free Energy Calculations
The Gibbs free energy change is attributable to two factors:
Enthalpy Factor (∆H˚) - A measure of the change in energy locked up in the
bonds; also called the Heat of Reaction , and,
Entropy Factor (∆S˚) - A measure of the change in molecular disorder or
freedom.
∆G˚ = ∆H˚ - T∆S˚
For the reaction described above ∆H˚ = -18 Kcal/mole and ∆S˚ = + 13 eu ( entropy is
expressed as entropy units, eu, which mean cal/ K-mol). The driving force for the reaction comes
mostly from bond-energy changes. A carbon-oxygen bond is stronger than a carbon-chlorine
bond. The formation of stronger bonds is usually an important component of the driving force of a
reaction.
c.
Bond Dissociation Energies
The amount of energy required to break a bond and produce radical fragments is termed the
Bond Dissociation Energy, symbolized by DH˚. Since energy is released when a bond is
formed (negative Enthalpy), and absorbed when it is broken (positive Enthalpy), the bond
dissociation energy DH˚ is positive on bond breaking and negative on bond forming. In a typical
reaction in which bonds are broken and new bonds are formed, the overall Enthalpy of Reaction is
a function of all the bonds broken and formed:
∆H˚ = (Sum of DH˚ for bonds broken) - (Sum of DH˚ for bonds formed)
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Potential Function for diatomic hydrogen molecule (H2).
E
N
E
R
G
Y
H
+
H
Separated hydrogen atoms
BOND DISSOCIATION ENERGY
Energy amount required to
break H-H bond
Bond Length value H-H
INTERNUCLEAR DISTANCE
H2
2H
∆H = DH = +104 Kcal/mol (Energy Absorbed)
2H
H2
∆H = DH = -104 Kcal/mol
(Energy Released)
In a reaction where only one bond is broken or formed, the Enthalpy of
Reaction is equal to the Bond Dissociation Energy
Bond Dissociation Energy
HO- + CH3-Cl
C-Cl Bond Broken
CH3-OH + Cl-
DH Kcal/mol
C-Cl
81
C-O
99
C-O Bond formed
∆H = Bonds Broken - Bonds Formed
= 81-99 = -18 Kcal/mol
Calculation of Enthalpy of Reaction
4.
Reaction Kinetics
The reaction of hydrogen and oxygen:, 2 H2 + O2 => 2 H 2O ∆G˚ = - 44 Kcal /mol
has a very large, exothermic driving force. Yet the reaction as written is extremely slow, in fact
non-existent, at room temperature. Thermodynamics will tell us whether a reaction will proceed at
room temperature, it does not tell us at what rate it will occur. Kinetics is the branch of science
which studies the rate of reactions.
In order for a reaction to occur, reactant molecules must collide, energy is transferred
during this collision and reorganization of bonds and atoms must occur. Reactions generally
involve an energy barrier that must be surmounted in going from reactants to products. This
barrier exists because molecules tend to repel one another, and this repulsion must be overcome by
forcing the reactants together so that bond reorganiztion can occur. The energy barrier is
called the energy of activation, (∆G ‡ ). A graphical depiction of the energy changes that
occur in a given chemical reaction is called a reaction energy diagram, or, reaction profile. The
vertical axis of the profile represents total energy; the horizontal axis represents reaction progress
from reactant (left side of plot) to products (right side of plot).
a.
Transition State Theory
The difference in stability between products and reactants is determined by ∆G˚, which
specifies what the value of an equilibrium constant would be for the reaction. This value says
absolutely nothing about the rate at which a given chemical reaction will occur. The rate of a
reaction can be predicted by employing the points of Transition State Theory.
i.
The rate of a chemical reaction is specified by a an equation known as the Rate
Law. For a simple reaction A + B => C the Rate Law would be:
∆[C]/∆t = k[A][B]
ii.
The rate constant is a function of the activation energy by the following expression:
k = e -∆G‡/RT
The consequences to the above expression are two fold:
1. The larger the activation barrier (∆G ‡ ), the slower the rate.
2. The higher the temperature, the faster the reaction rate.
The rates for forward and reverse directions of the reaction are a function of the
activation barriers for the forward and reverse directions.
iii.
As reactants change into products they pass through a high energy, unstable state of
maximum free energy called the transition state, (T . S . ).
iv.
The equilibrium constant is a function of the rate of reaction in both the forward and
reverse reaction:
K eq = k forward /k reverse
Likewise the equilibrium constant is a function of the activation barriers in the
forward and reverse direction.
transition state
E
N
E
R
G
Y
Activation energy
for reverse
direction
products
reactants
Reaction Coordinate
Reaction Profile of a Chemical Reaction
b.
Activation energy
for forward
direction
Multistep Reactions
∆G
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Consider a multi-step reaction: A + B = = > C = = > D . A free energy minimum
between reactants A&B and Products D exists and is called an intermediate (C). An intermediate
is an isolatable species, and as such, is different from a transition state. Reactions with an
intermediate have at least two transition states. The overall rate for a multi-step reaction is the rate
for the slowest step in the forward direction. This Rate Determining Step corresponds to the
transition state with the greatest free energy (tallest barrier).
TS #1
E
N
E
R
G
Y
TS #2
C
A + B
intermediate
D
reactants
products
The Rate Determining Step is A + B ==> C
REACTION COORDINATE
TS #2
TS #1
E
N
E
R
G
Y
C
A + B
intermediate
D
reactants
products
The Rate Determining Step is C ==> D
REACTION COORDINATE
Free Energy Diagram of a Multi-Step Reaction
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