John E.
McMurry
www.cengage.com/chemistry/mcmurry
Chapter 6
An Overview of
Organic Reactions
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Why we study this chapter ??
§ All chemical reactions follow the same “rules.”
§ To understand the organic chemistry, it is
necessary to know not just what occurs, but
also why and how chemical reactions take
place.
§ We will start with an overview of the
fundamental kind of organic reactions.
§ We’ll be ready to begin studying the details of
organic chemistry
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Learning Objectives
(6.1) Kinds of organic reactions
(6.2) How organic reactions occur: Mechanisms
(6.3) Radical reactions
(6.4) Polar reactions
(6.5) An example of a polar reaction: Addition of HBr to ethylene
(6.6) Using curved arrows in polar reaction mechanisms
(6.7) Describing a reaction: Equilibria, rates, and energy changes
(6.8) Describing a reaction: Bond dissociation energies
(6.9) Describing a reaction: Energy diagrams and transition states
(6.10) Describing a reaction: Intermediates
(6.11) A comparison between biological reactions and laboratory
reactions
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1. Kinds of Organic Reactions
§ Addition reactions: Two reactants combining to
form a single product with no “left over”
§ Elimination reactions: Single reactant splitting into
two products
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Kinds of Organic Reactions
§ Substitution reactions: Two reactants exchanging
parts to form two new products
§ Rearrangement reactions: Single reactant yielding
an isomeric product through reorganization of its
bonds and atoms
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Worked Example
§ Classify each of the following reactions as an addition,
elimination, substitution, or rearrangement
§ a)CH3Br + KOH → CH3OH + KBr
§ b) CH3CH2Br → H2C═CH2 + HBr
§ c) H2C═CH2 + H2 → CH3CH3
§ Solution:
§ a)CH3Br + KOH → CH3OH + KBr (Substitution)
§ b) CH3CH2Br → H2C═CH2 + HBr (Elimination)
§ c) H2C═CH2 + H2 → CH3CH3 (Addition)
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2. How Organic Reactions Occur:
Mechanisms
§ Reaction mechanism: Overall description of a
reaction process
§ Reactions occur in defined steps that lead from
reactant to product
§ Must account for all reactants and products
§ Chemical reactions involve bond-breaking and
bond-making
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How Organic Reactions Occur:
Mechanisms
§ Bond formation or breakage can be symmetrical or
unsymmetrical
§ Symmetrical cleavage - Homolytic
§ Unsymmetrical cleavage - Heterolytic
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How Organic Reactions Occur:
Mechanisms
§ Curved arrows indicate breaking and forming of
bonds
§ Arrowheads with a half head (fish-hook)
indicate movement of one electron in the
symmetrical process
§ Arrowheads with a complete head
indicate movement of two electrons in the
unsymmetrical process
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How Organic Reactions Occur:
Mechanisms
§ Radical reactions: Processes that involve
symmetrical bond-breaking and bond-making
§ Radical: Neutral chemical species containing odd
number of electrons
§ Has a single, unpaired electron in one of its
orbitals
§ Polar reactions: Processes involving
unsymmetrical bond-breaking and bond-making
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3. Radical Reactions
§ Not as common in comparison to polar reactions
§ Radicals react to complete electron octet of
valence shell
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Radical Reactions
§ A radical can add to an alkene to give a new radical,
causing an addition reaction
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Radical Reactions
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Radical Reactions
§ Steps required for methyl chlorination
§ Initiation
§ Propagation
§ Reaction with molecule to generate radical
Repeat (a) and (b)
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Radical Reactions
§ Termination
§ Combination of two radicals to form a stable product
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Worked Example
§ Radical chlorination of alkanes is not generally
useful because mixtures of products often
result when more than one kind of C-H bond is
present in the substrate. Draw and name all
monochloro substitution products C6H13Cl you
might obtain by reaction of 2-methylpentane
with Cl2.
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Worked Example
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Worked Example
§ Using curved fishhook arrows, propose a
mechanism for the formation of the
cyclopentane ring of prostaglandin H2
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Worked Example
§ Solution:
§ The tails of the arrows show the location of the bond
to be broken
§ The heads show where the electrons are moving
§ The reaction is a radical addition to a double bond
§ It is a rearrangement
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Polar Reactions
§ Molecules can contain local unsymmetrical electron
distributions : Causes bond polarity
§ Bonds in functional groups are polar
§ Carbon atoms bonded to electronegative atoms
have a partial positive charge
§ Carbon atoms bonded to metals have a partial
negative charge
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Polar Reactions
§ polar covalent bonds
§ unsymmetrical electron distribution due to difference
in electronegativity
§ electrotatic potential maps
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Table 6.1 - Polarity Patterns in Some
Common Functional Groups
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Polar Reactions
Increase in the bond polarity
by acid catalyst
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Polar Reactions
§ Polarizability: Tendency of atoms in a molecule to
undergo polarization
§ Larger atoms, easily polarizable (loosely held e-)
§ Smaller atoms, less polarizable (higher EN)
• Electronegativity of C : 2.0, S : 2.5, I : 2.5
• C-S, C-I bond is nonpolar, but usually
react as if they were polar due to the
high polarizability of S, I
S vs. O I vs. Cl
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Polar Reactions
§ Chemical reactivity is affected by bond polarity
§ Electron-rich sites react with electron-poor sites
§ Bond are made when electron-rich atom donates a
pair of electrons to an electron-poor atom
§ Bond are broken when one atom leaves with both
electrons from the former bond.
§ Movement of an electron pair is indicated by using a
curved, full-headed arrow
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4. Polar Reactions
§ Nucleophile: Electron-rich species that donate
electron pairs to electrophile in a polar bond-forming
reaction (Lewis base)
§ Electrophile: Substances that accept electron pairs
from a nucleophile (Lewis acid)
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Figure 6.1 - Some Nucleophiles
and Electrophiles
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Worked Example
Which of the following species is likely to behave as a
nucleophile and which as an electrophile?
(a) NO2+(b) CN- (c) CH3NH2 (d) (CH3)3S+
Strategy
A nucleophile has an electron-rich site, either because it
is negatively charged or because it has a functional group
containing an atom that has a lone pair of electrons.
An electrophile has an electron-poor site, either because
it is positively charged or because it has a functional
group containing an atom that is positively polarized.
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Worked Example
Solution
(a) NO2+ (nitronium ion) is likely to be an electrophile
because it is positively charged.
(b) :C≡N-(cyanide ion) is likely to be a nucleophile
because it is negatively charged.
(c) CH3NH2 (methylamine) might be either a nucleophile
or an electrophile, depending on the circumstances. The
lone pair of electrons on the nitrogen atom makes
methylamine a potential nucleophile, while positively
polarized N-H hydrogens make methylamine a potential
acid (electrophile).
(d) (CH3)3S+(trimethylsulfonium ion) is likely to be an
electrophile because it is positively charged.
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Worked Example
Problem6-4
Which of the following species are likely to be nucleophiles and which
electrophiles? Which might be both?
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Worked Example
§ An electrostatic potential map of boron trifluoride is
shown
§ Is BF3 likely to be a nucleophile or an
electrophile?
§ Draw a Lewis structure for BF3
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Worked Example
§ Solution:
§ The electrostatic potential map indicates that it is
electron-poor (blue)
§ BF3 is likely to be an electrophile
§ Lewis structure
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An Example of a Polar Reaction:
Addition of HBr to Ethylene
§ Electrophilic addition reaction
§ p part results from p–p overlap
§ σ results from sp2–sp2 overlap
§ Double bond is more accessible to approaching
reactants than a single bond
§ More electron-rich
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Figure 6.2 - A Comparison of Carbon–
Carbon Single and Double Bonds
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Figure 6.3 - Mechanism
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Mechanism of Addition of HBr to
Ethylene
§ Polar reactions occur by combination of an electron-
rich site of a nucleophile and an electron-deficient
site of an electrophile
§ Carbocation: Substance that contains a trivalent,
positively charged carbon atom having six electrons
in its outer shell
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Worked Example
§ What product would you expect from reaction of
cyclohexene with HBr and HCl?
§ Solution:
§ Reaction is an electrophilic addition reaction
§ Halogen acid adds to a double bond to produce a
haloalkane
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Worked Example
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Worked Example
Show the mechanism of the reaction
Solution
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6. Rules for Using Curved Arrows
§ Electrons move from a nucleophilic source to an
electrophilic sink
§ The nucleophilic site can be neutral or negatively
charged
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Rules for Using Curved Arrows
§ The electrophilic site can be neutral or positively
charged
§ The octet rule should be followed
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Worked Example
§ Show the flow of electrons using curved arows
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Worked Example
§ Add curved arrows to the following polar
reaction to indicate the flow of electrons
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Worked Example
§ Solution:
§ A double bond forms between oxygen and
carbon
§ C–Cl bond is broken
§ Electrons move from oxygen to form the double
bond and from carbon to chlorine
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
§ To reach equilibrium, reactions go in either forward
or reverse directions
§ The multiplied concentrations of the products
divided by the multiplied concentrations of the
reactant is the equilibrium constant, Keq
§ Each concentration is raised to the power of its
coefficient in the balanced equation
aA + bB cC + dD
c d
éëC ùû éë D ùû
Keq = a b
éë A ùû éë Bùû
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
§ If value of Keq is > 1
§ Indicates that product concentration term is larger
than the reactant concentration term
§ Reaction takes place from left to right
§ If Keq is 1
§ Quantity of reactant and product present at
equilibrium is same
§ If value of Keq is < 1
§ Reaction takes place in the reverse direction
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Equilibrium constant , Keq
§ 99.999 99 % of ethylene is converted into bromoethane
§ If Keq > 103, the amount of reactant left over will be barely
detectable (less than 0.1%)
§ The magnitude of Keq depends on the energy state of
reactants and products
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
§ Gibbs free energy (ΔG): Change in energy that
occurs during a chemical reaction
§ ΔG = Gproducts - Greactants
§ Energy is released on the favored side of an
equilibrium reaction
§ Exergonic: Reaction that has negative free energy
change and is therefore spontaneous
§ Energy is lost
§ Endergonic: Reaction that has positive free energy
change
§ Energy is absorbed
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
§ Standard free energy change at 1 atm pressure
and 298 K is denoted as ΔG°
§ Relationship between free energy change and
an equilibrium constant is:
§ ΔG° = - RT ln Keq
§ Where,
§ R = 1.987 cal/(K · mol)
§ T = Temperature in Kelvin
§ ln Keq = Natural logarithm of Keq
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
ΔGo = ΔHo – TΔSo
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Describing a Reaction: Equilibria,
Rates, and Energy Changes
§ Enthalpy change (ΔH): Measure of change in total
bonding energy during a reaction
§ Called heat of reaction
§ Exothermic: Reaction that releases heat
§ Endothermic: Reaction that absorbs heat
§ Entropy change (ΔS): Measure of the change in the
amount of molecular randomness
§ Keq tells the position of the equilibrium
§ Amount of product that is theoretically possible
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Gibb’s Free energy
§ ΔG = ΔH - TΔS
§ ΔH : measure bond strength
( - ) : products > reactants
( + ) : reactants > products
§ ΔS : degree of freedom
(-):A+B→C
(+):A→B+C
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Table 6.2 - Explanation of Thermodynamic
Quantities: ΔG°= Δ H°- T Δ S°
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Worked Example
§ Which reaction is likely to be more exergonic,
one with Keq = 1000 or one with Keq = 0.001?
§ Solution:
§ ΔG° = -RT ln Keq
§ Large Keq is related to a large negative ΔG°
§ A favorable reaction
§ Therefore, a reaction with Keq = 1000 is more
exergonic than a reaction with Keq = 0.001
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8. Describing a Reaction: Bond
Dissociation Energies
§ Bond dissociation energy (D): Amount of
energy required to break a given bond to
produce two radical fragments when the
molecule is in the gas phase at 25˚ C
§ Energy is determined by the type of bond
§ Changes in bonds can be used to calculate net
changes in heat
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Bond Dissociation Energy
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Worked Example
Problem6-10
Which reaction is more energetically favored, one with ΔG°= + 44 kJ/mol
or one with ΔG°= − 44 kJ/mol?
Problem6-11
Which reaction is likely to be more exergonic, one with Keq = 1000 or one
with Keq = 0.001
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9. Describing a Reaction: Energy
Diagrams and Transition States
§ Transition state: Highest
energy point in a reaction
step
§ Activation energy, ΔG‡:
Energy required to go
from reactant to transition
state
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Describing a Reaction: Energy
Diagrams and Transition States
§ In the addition of HBr
§ Transition-state structure for the first step
§ p bond between the carbons begins to break
§ C–H bond is partially formed
§ H–Br bond begins to break
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Describing a Reaction: Energy
Diagrams and Transition States
§ Once the transition state is reached,
the reaction may:
§ Continue to give the carbocation product
§ Revert back to reactants
§ Every reaction has its own energy profile
§ ΔG‡ for organic reactions : 40 ~ 150 kJ/mol
(10 ~ 35 kcal/mol)
§ Ethylene + HBr : ΔG‡ = 140 kJ/mol
§ ΔG‡ < 80 kJ/mol : Reactions take place at RT
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Figure 6.6 - Some Hypothetical
Energy Diagrams
fast exogonic slow exogonic
fast endergonic slow endergonic
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Worked Example
§ Which reaction is faster, one with ΔG‡ = +45 kJ/mol
or one with ΔG‡ = +70 kJ/mol?
§ Solution:
§ Larger value for ΔG‡ indicates a slower reaction
§ Therefore, reaction with ΔG‡ = +45 kJ/mol is faster
than a reaction with ΔG‡ = +70 kJ/mol
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10. Describing a Reaction:
Intermediates
§ If a reaction occurs in more than one step, it
must involve species that are neither the
reactant nor the final product
§ Called reaction intermediate
§ Each step has its own free energy of activation
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Figure 6.7 - An Energy Diagram
for the Reaction of Ethylene with HBr
rate determining step
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Enzyme-catalyzed biological reaction
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Worked Example
Sketch an energy diagram for a one-step reaction that is fast and highly exogonic.
• small ΔGǂ
• large negative ΔGo
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Worked Example
§ Sketch an energy diagram for a two-step
reaction in which both steps are exergonic
§ Second step has a higher-energy transition state
than the first
§ Label the parts of the diagram corresponding to
reactant, product, intermediate, overall ΔG‡, and
overall ΔG°
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Worked Example
§ Solution:
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Comparison Between Biological
Reactions and Laboratory Reactions
§ Laboratory reactions are often carried out in an
organic solvent
§ Biological reactions occur in an aqueous
medium inside cells
§ Active site: Pocket in an enzyme where a
substrate is bound and undergoes reaction
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Comparison Between Biological
Reactions and Laboratory Reactions
§ Laboratory reactions
§ Often done using relatively simple reagents
§ Catalyst might be used
§ Biological reactions
§ Involve relatively complex reagents called
coenzymes
§ Enzymes provide an alternative mechanism that
makes life possible
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Figure 6.9 - Models of Hexokinase in
Space-filling and Wire-frame Formats
hexokinase
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Biological Reactions
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Where Do Drugs Come From ?
Gardasil
(Investigational New Drug) 임상시험 승인 신청
70% 33% 25% 20%
New Drug Application
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Summary
§ Common kinds of reactions: Addition reactions,
elimination reactions, substitution reactions, and
rearrangement reactions
§ Mechanism describes of how a reaction occurs
§ Mechanisms by which most reactions take
place: radical and polar
§ Polar reactions occur due to an attractive
interaction between a nucleophilic site in one
molecule and an electrophilic site in another
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Summary
§ Position of a chemical equilibrium is determined
by the value of the free-energy change (ΔG)
§ Enthalpy (ΔH) corresponds to the net change in
strength of chemical bonds broken and formed
during the reaction
§ Entropy (ΔS) corresponds to the change in the
amount of molecular randomness during the
reaction
§ Exergonic reactions are that have negative
values of ΔG, release energy
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Summary
§ Reactions that have positive values of ΔG and
absorb energy are endergonic
§ Transition state is an activated complex
occurring at the highest-energy point of a
reaction
§ Amount of energy needed by reactants to reach
this high point is the activation energy, ΔG‡
§ Reactions take place in more than one step and
involve the formation of a reaction intermediate
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