Download 24_Lecture

Organic Chemistry
6th Edition
Paula Yurkanis Bruice
Chapter 24
Catalysis
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Catalyst
A catalyst is a substance that increases the rate of
a reaction without itself being consumed or
changed
A catalyst increases the rate of the reaction by
lowering the DG‡ of the reaction
A catalyst can decrease DG‡ of the reaction by one
of three different ways
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The Catalyst Converts the Reactant to
a Less Stable Species
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The Catalyst Stabilizes the Transition State
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The Catalyst Changes the
Mechanism of the Reaction
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A catalyst can provide a more favorable pathway
for an organic reaction by:
• Increasing the susceptibility of an electrophile to
nucleophilic attack
• Increasing the reactivity of a nucleophile
• Increasing the leaving ability of a group by
converting it to a weaker base
• Increasing the stability of a transition state
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Acid Catalysis
Mechanism for acid-catalyzed ester hydrolysis
A proton is donated to the reactant:
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A catalyst must increase the rate of a slow step:
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In specific-acid catalysis, the proton is fully transferred
before the slow step of the reaction
In general-acid catalysis, the proton is transferred during
the slow step of the reaction
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Comparing Specific-Acid Catalysis with
General-Acid Catalysis
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A specific-acid catalyst must be a strong acid
A general-acid catalyst is usually a weaker acid
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Base Catalysis
A base catalyst increases the rate of the reaction by
removing a proton from the reaction:
specific-base-catalyzed dehydration
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The rate of the reaction is accelerated by stabilization
of the transition state:
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In specific-base catalysis, the proton is completely
removed before the slow step of the reaction
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In general-base catalysis, the proton is removed during
the slow step of the reaction:
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Nucleophilic Catalysis
• Increases the rate of a reaction by acting as a
nucleophile, thereby completely changing the reaction
mechanism
• Forms an intermediate by forming a covalent bond with
the reactant
• Also known as covalent catalysis
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Imidazole catalyzes ester hydrolysis via an acyl
intermediate:
Imidazole increases the rate of ester hydrolysis
because of both its nucleophilicity and its leaving
ability
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Metal-Ion Catalysis
Metal ions are Lewis acids:
electrophilic
catalyst
A. The metal ion makes a reaction center more susceptible to
receiving electrons
B. The metal ion makes the leaving group a weaker base
C. The metal ion increases the nucleophilicity of water
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Metal-bound hydroxide ions are better nucleophiles than
water
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Metal-Ion-Catalyzed Decarboxylation
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Metal-Ion-Catalyzed Ester Hydrolysis
• The metal-bound hydroxide is a better nucleophile
than water.
• The metal ion also decreases the basicity of the
leaving group.
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• The relative rates are also called the effective molarity.
• The effective molarity is the advantage given to a
reaction by having the reacting groups in the same
molecule.
• The relative rate of reactant D is higher than the
relative rate of B because the groups in D are less
apt to adopt an unfavorable conformation for the
reaction.
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Intramolecular Catalysis
• Putting a reacting group and a catalyst in the same
molecule increases the rate of the reaction.
• Intramolecular catalysis is also known as anchimeric
assistance.
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The trans isomer reacts much faster than the cis isomer:
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The rate of phenyl acetate hydrolysis is enhanced by
an intramolecular general base catalysis:
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In the presence of nitro groups, the ortho-carboxyl
substituent acts as an intramolecular nucleophilic
catalyst:
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An Intramolecular Metal-Ion Catalysis
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Most Biological Catalysts Are Enzymes
The reactants are called substrates
The substrate specifically fits and binds to the active site
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Hexokinase undergoes a conformational change upon
binding to a substrate:
red: before substrate binding
green: after substrate binding
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Factors Contributing to the
Catalytic Ability of Enzymes
• Reacting groups are brought together at the active site
in the proper orientation for reaction.
• Some of the amino acid side chains serve as
catalysts.
• Many enzymes have metal ions at their active sites that
act as catalysts.
• Amino acid side chains can stabilize transition states
and intermediates.
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Proposed Mechanism of Carboxypeptidase A
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The binding pocket at the active site of serine proteases
dictates substrate specificity:
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Proposed Reaction Mechanism of a Serine Protease
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Lysozyme Is an Enzyme That
Destroys Bacterial Cell Walls
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The amino acids at
the active site of
lysozyme are
involved in binding
the substrate
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Proposed Reaction Mechanism for Lysozyme
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The pH–rate profile of an enzyme is a function of the
pKa values of the catalytic groups in the enzyme:
a group is
catalytically
active in its basic
form
a group is
catalytically
active in its acidic
form
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Glucose-6-phosphate Isomerase
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Mechanism for Aldolase
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