Module G

Chemical Reactions and Mechanisms

Bruice’s Organic Chemistry: Chapters 5

Learning Outcomes:
1. What reaction changes are we interested in?
2. What are terms to describe chemical reactivity and thermodynamics?
3. What are nucleophiles and electrophiles in polar reactions?
4. How to draw mechanisms showing electron flow, bond formation and cleavage?

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 Chemical Reactions:
What do we want to know?
 Regarding reactions, we
are interested in changes
at the molecular level:

Krebs Cycle

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 Chemical Reactions:
What do we want to know?
 Regarding reactions, we
are interested in changes
at the molecular level:

Krebs Cycle

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 Review

Kinds of Organic Reactions

 We can classify reactions by describing the overall changes
from organic starting material to product due to bonding:

 Addition reactions – two molecules combine

 Elimination reactions – one molecule splits into two
 Substitution – parts from two molecules exchange
 Rearrangement reactions – a molecule undergoes changes in
the way its atoms are connected

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 What kind of reactions?

COOCH3 COOCH3 Addition

heat
+
H3COOC COOCH3

HO OH catalyst O Elimination
H H + H2O

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 What kind of reactions?
O
CH3
O S HN
NH Na O Substitution
+ + Na OSO2CH3

O HO
Rearrangement
heat

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 Review

Kinds of Organic Reactions

 We can describe additional kinds of reactions by paying
attention to other aspects of molecular change:

 Oxidation reactions – the product has a higher oxidation level

 Reduction reactions – the product has a lower oxidation level

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 Oxidations and Reductions in Organic Chemistry
 In inorganic chemistry, we say that oxidation occurs when a
metal loses electrons
 Eg. Mg0 → Mg 2+

 In inorganic chemistry, we say that reduction occurs when a

metal gains electrons:
 Eg. MnO4- → MnO2

 In organic chemistry, we usually do not express the oxidation

state of carbon numerically
 Carbon is always covalently bonded to other atoms and does not
exist alone as metal ions do
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 Oxidation Levels
 Instead of oxidation states, we talk about the oxidation levels of
organic compounds
 Functional groups are associated with specific oxidation levels

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 Oxidation Levels
 Functional groups of high oxidation levels are bonded to oxygen
or other electronegative atoms, such as halides, nitrogen
 Functional groups of low oxidation levels are bonded to more
hydrogen

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 Oxidation & Reduction in Organic Chemistry
 An oxidation reaction occurs when there is a loss of electron-density
at carbon
 This occurs when carbon becomes bonded to more electronegative atoms,
such as oxygen, nitrogen or halogens
Oxidation: break C-H (or C-C) and form C-O, C-N, C-X

 A reduction reaction occurs when there is a gain of electron-density

at carbon
 This occurs when carbon becomes bonded to less electronegative atoms,
such as hydrogen (proton)
Reduction: break C-O, C-N, C-X and form C-H (or C-C)
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 Oxidation and Reduction in Organic Chemistry
 Examples:
Imaginary Electron counting

Substitution reaction

Addition reaction
Substitution (at C)
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 Module G

Chemical Reactions and Mechanisms

Bruice’s Organic Chemistry: Chapters 5

Learning Outcomes:
1. What reaction changes are we interested in?
2. What are terms to describe chemical reactivity and thermodynamics?
3. What are nucleophiles and electrophiles in polar reaction mechanisms?
4. How to draw mechanisms showing electron flow, bond formation and cleavage?

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 Chemical Reactions:
What do we want to know?
 Regarding reactions, we are interested in changes at the
molecular level:
(1) What are the changes in the molecular structure, and
(2) WHY and HOW it happened

Reaction mechanism
Reaction thermodynamics and kinetics

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 Review
Terms in Reaction
Thermodynamics and Kinetics
 You should be familiar with these terms:
 Gibbs free energy
 Enthalpy, Entropy
 Rate Law
 First order, second order reactions
 Rate determining step
 Activation energy, transition state
 Here we will apply them to reactions of organic compounds

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 Review
Terms in Reaction Thermodynamics
Question: Will a reaction occur? How do we know?

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 Review
Reaction Coordinate Diagrams
 We are interested in the energy
corresponding energy
changes as the reaction progresses
changes on the y-axis
Shows the

Shows the progress

of the reaction on
the horizontal x-axis
(reaction coordinate)
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Reaction coordinate

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 Review

Reaction Coordinate Diagrams

 There are two free energies differences we need to read:
  G° = Energy difference between products and starting materials at
equilibrium
  G° >0: Starting materials more stable and favored than products,
reaction is not spontaneous
  G° <0: Products more stable and favored than starting materials,
reaction is spontaneous
  G‡ = Energy difference between starting materials and transition state,
always > 0
 Tells us how fast the reaction proceeds

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 Review

Equilibrium vs. Rate

 Knowing the value of Keq and
 G° only tells us whether
equilibrium favors product
G‡
formation theoretically
 It does not tell us how fast the
G‡
reaction proceeds to reach this
equilibrium, ie. the reaction reactants
rate depends on G‡ - G
 If a reaction is very, very slow,
we still would not get product products

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 Exergonic reactions (ΔG° <0) Endergonic reactions (ΔG° >0)

Progress of the reaction

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Progress of the reaction

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 Review

Reaction Coordinate Diagram

 Free energy of Activation (G‡):

 Energy difference
between reactants and
transition state
 If this can be
surmounted by the
reactants, then the
reaction can proceed

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 Review

Transition State Structure

 Transition state:
 Structure at the point
of maximum energy Transition
state
 It has partial bond
formation and
cleavage and is
unstable; cannot be
isolated or observed

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 Transition State Structure
 Once the transition state
is reached, the reaction
can continue to product or
revert back to starting
materials
 But if equilibrium favors
products, eventually
products would
predominate

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 Steps in Reactions
 A reaction can occur in one step, or a number of steps
 A step is ONE bond forming or breaking event that leads to an
new molecule

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 Reaction Coordinate Diagram For Two-step Reaction
Each step has
Intermediate
its own
activation G‡

Reactants
Step 1 is the
rate-determining step Products

Step 1 Step 2 25

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 Review

Multistep reactions
 If a reaction proceeds by more than one step:
 The reaction would generate compounds which are neither the reactant nor
the final product, and are called reaction intermediates or simply
“intermediates”

 The step with the highest energy

transition state is the slowest step, ie.
it is the rate-determining (rate-
limiting) step
 In this reaction, the greatest G‡ is from
A → B, but the rate determining step is
B→C

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 Review

Effect of Heating a Reaction

 Reactions with high
G‡ proceed slowly

 Molecules undergo more collisions

 A greater number of molecules have the energy to overcome activation energy
barrier
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 Review
Catalysis
 In addition to heating, reactions with
high activation energies may be able to
proceed through an alternative
pathway (a catalytic pathway) having
steps with lower activation energies
 The same reagents still give the same
products, and the catalyst is not
consumed

B A B
A
A
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 Biological Reactions
 Reactions in living organisms are like reactions on the bench
 The catalysts are usually proteins called enzymes
 Enzymes facilitate an alternative catalysis mechanism that allows
the reaction to proceed under conditions compatible with life

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 Biological Reactions
 Reactions in living organisms are like reactions on
the bench, but there are also differences

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 Reaction Selectivity
 When we put reactants together,
many combinations do not undergo
just a single reaction
 Real reactions typically do not convert
reactants to one product in 100% yield
 Sometimes more than one reaction is
possible
 Alternative products arising from
another undesired reaction under the
same conditions are called side products;
these are not the same as byproducts
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 Types of selectivity
 But even if only one/intended reaction occurs, more than
one product is still possible!
A regioselective reaction on
“regioisomers”
a functional group:

A stereoselective reaction on
a functional group:

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 Types of selectivity
 But even if only one/intended reaction occurs, more than
one product is still possible!

“regioisomers” A regioselective
reaction on a
functional group

A stereoselective
reaction on a
functional group

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 Module G

Chemical Reactions and Mechanisms

Bruice’s Organic Chemistry: Chapters 5

Learning Outcomes:
1. What reaction changes are we interested in?
2. What are terms to describe chemical reactivity and thermodynamics?
3. What are nucleophiles and electrophiles in polar reaction mechanisms?
4. How to draw mechanisms showing electron flow, bond formation and cleavage?

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 How Organic Reactions Occur: Mechanisms
 We see the hands of a watch move but the mechanism
behind the face is what causes the movement

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 How Organic Reactions Occur: Mechanisms
 In an organic reaction, we see the chemical transformation that
has occurred

 A reaction involves changes in bonding from starting material to

product: bonds have been broken and new bonds have been made
 The mechanism describes the steps of the changes in bonding :
 How many separate events?
 In what order?
 How fast relatively?
 Stereochemistry?

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 Steps in Mechanisms
 A reaction mechanism can be one step or a number of steps
 A step is ONE bond forming or breaking event that leads to an
intermediate or product
 When bond-making and/or breaking occur sequentially, the
reaction is said to be stepwise
 When bond-making and/or breaking occur at the same time, the
reaction is concerted
 Because bond-making/breaking involves relocation of electrons,
the complete mechanism must show electron movement

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 Steps in Mechanisms
 A reaction mechanism can be one step or a number of steps

Stepwise mechanism:

Concerted mechanism:

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 How to Show Electron
Movement in Mechanisms
 A reaction has occurred: bonding has changed to generate new products

 Curved arrows indicate electron flow

 Arrows show the direction of electron flow
 Arrowheads with a complete head indicate electron pair movement
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 Polar Reactions
 Reactions in organic
chemistry typically involve
electron pair movement
and transfer, ie. polar
reactions, because
molecules have
unsymmetrical local
electron distributions, due
to differences in
electronegativities
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 Polar Bonds And Reagents
 Electronegativity differences leads to a partial negative charge
(greater electron density) on the more electronegative atom,
and a corresponding deficiency (partial positive charge) on the
less electronegative atom

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 Polar Bonds And Reagents
 Polar bonds can further increase in polarity by interacting
with solvents, acids and bases

δ

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 Generalized Polar Reactions
 Polar reactions occur between regions of high electron and
low electron density
 A nucleophile (an electron-rich species, Lewis base) donates
electrons to an electrophile (an electron-poor species, Lewis acid)
 Curved arrows showing “electron pair movement” keep track of
changes in bonding

The combination of the two

species resulted in the
formation of this new bond,
by sharing an e pair

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 Examples: Nucleophiles

Lewis bases

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 Examples: Electrophiles

Lewis acids

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 Examples: Nucleophiles, Electrophiles
 It is possible for a compound to act as a nucleophile or an
electrophile: this depends on the reacting partners
Nucleophilic

Electrophilic

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 Module G

Chemical Reactions and Mechanisms

Bruice’s Organic Chemistry: Chapters 5

Learning Outcomes:
1. What reaction changes are we interested in?
2. What are terms to describe chemical reactivity and thermodynamics?
3. What are nucleophiles and electrophiles in polar reaction mechanisms?
4. How to draw mechanisms showing electron flow, bond formation and cleavage?

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 How to Draw Reaction Mechanisms: Rule 1
 The electron arrow starts from the nucleophilic source to show the donation
of the electron pair to the electrophilic sink
 The arrows show electron pair movement, NOT atom movement—so
arrow must originate from lone pair, negative charge or bond

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 How to Draw Reaction Mechanisms: Rule 2
 Keep track of valencies and charges, make sure charges are
conserved !
 They should be balanced

This hydrogen already has two electrons.

When another electron pair moves to the hydrogen
from the double bond, the electron pair in the HBr
bond must leave.
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 Draw Mechanisms Correctly (1)

 Solution:

Point: must identify the correct source of

electrons for bond-making
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 Draw Mechanisms Correctly (2)

 Solution:

Point: must differentiate positive charges—is it from having

too few bonds, or overcommitment of electrons?

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 Draw Mechanisms Correctly (3)

 The arrows show

electron pair
movement, not atom
movement
 Point: Arrow must
originate from lone
pair, negative charge
or bond

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 Draw Mechanisms Correctly (3)
 The arrows show electron pair movement, not atom movement
 Arrow must originate from lone pair, negative charge or bond

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 Practice Drawing Electron Flow!
 Recommended: Essential Skill Tutorial on p. 261 of the
Textbook, and the accompanying worked problems to
practice drawing electron flow using curved arrows

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 Exercise 1:
 Show the correct electron flow to account for this transformation.
You should be able to do this based on bonding considerations,
even though you do not know the reaction

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 Review/Summary of Reaction Terms
 Reaction coordinate diagram shows:
 Steps, transition states, free energies, intermediates, rate determining
step, catalysis—as starting materials are converted to products
 A reaction mechanism--shows electron movement and accounts
for bond formation and cleavage in reactions
 Polar reactions involve nucleophiles donating electron pair to
electrophiles to make new bonds

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 Review/Summary of Reaction Terms
 Concerted, stepwise reactions
 Addition, elimination, substitution and rearrangement reactions
 Oxidation, reduction reactions in organic chemistry
 Oxidation levels
 Catalytic reactions
 Regioselective, stereoselective reactions

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 Module G

Chemical Reactions and Mechanisms

Bruice’s Organic Chemistry: Chapters 5

Check that you have achieved these learning outcomes, and can give examples to
explain and answer each of these questions:

1. What reaction changes are we interested in?

2. What are terms to describe chemical reactivity and thermodynamics?
3. What are nucleophiles and electrophiles in polar reaction mechanisms?
4. How to draw mechanisms showing electron flow, bond formation and cleavage?

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