Organic Chemistry 4th Edition

Paula Yurkanis Bruice

Chapter 24

Catalysis

Irene LeeCase Western Reserve

UniversityCleveland, OH

©2004, Prentice Hall

A catalyst is a substance that increases the rate of areaction without itself being consumed or changed

A catalyst increases the rate of the reaction by loweringthe ∆G‡ of the reaction

A catalyst can decrease ∆G‡ of the reaction by one of three different ways

Catalyst

The Catalyst Converts the Reactant to a Less Stable Species

The Catalyst Stabilizes the Transition State

The Catalyst Changes the Mechanism of the Reaction

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

Both the formation of the acyl imidazole and its subsequent hydrolysis are both faster than esterhydrolysis

Nucleophilic Catalysis

An Acid-Catalyzed Reaction

A proton is donated to the reaction

The acid increases the rates of both slow steps of thereaction

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

Compare Specific-Acid Catalysis with General-Acid Catalysis

A specific-acid must be a strong acid

A general-acid can be a weaker acid

Base Catalysis

A base catalyst increases the rate of the reaction by removing a proton from the reaction

specific-base catalyzed dehydration

The rate of the reaction is accelerated by stabilizationof the transition state

In specific-base catalysis, the proton is completely removed before the slow step of the reaction

general-base catalysis

In general-base catalysis, the proton is removed duringthe slow step of the reaction

Metal-Ion Catalysis

A. The metal ion increases the susceptibility of electron attack

B. The metal ion makes the leaving group a weaker base

C. The metal ion increases the nucleophilicity of water

An Example of a Metal-Ion-Catalyzed Reaction

Metal-Ion-Catalyzed Decarboxylation

Metal-Ion-Catalyzed Ester Hydrolysis

The metal-bound hydroxide is a better nucleophile thanwater

The metal ion also decreases the basicity of the leavinggroup

The relative rates are also called the effective molarity

The effective molarity is the advantage given to a reaction

The relative rate of reactant D is higher than the relativerate of B because the groups in D are less apt to adoptan unfavorable conformation for the reaction

Putting a reacting group and a catalyst in the samemolecule increases the rate of the reaction

Intramolecular catalysis is also known as anchimeric assistance

The trans isomer reacts much faster than the cis isomer

The rate of phenyl acetate hydrolysis is enhanced by an intramolecular general base catalysis

In the presence of nitro groups, the ortho-carboxylsubstituent acts as an intramolecular nucleophilic catalyst

An Intramolecular Metal-Ion Catalysis

Most Biological Catalysts Are Enzymes

The reactants are called substrates

The substrate specifically fits and binds to the active site

Hexokinase undergoes a conformational change uponbinding to a substrate

red: before substrate-bindinggreen: after substrate-binding

Important Features that Contribute 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 acids in the enzyme serve as catalytic groups; many enzymes have metal ions as catalysts

• Groups on the enzyme can stabilize the transition state of the reaction

Carboxypeptidase A catalyzes the hydrolysis of theC-terminal peptide

The binding pocket at the active site of serine proteasesdictates substrate specificity

The Proposed Reaction Mechanism of a Serine Protease

Lysozyme Is an Enzyme that Destroys Bacterial Cell Walls

The amino acids at the active site of

lysozyme are involved in binding

the substrate

The Proposed Reaction Mechanism for Lysozyme

The pH-rate profile of an enzyme is a function of thepKa values of the catalytic groups in the enzyme

a group iscatalytically

active in its basicform

a group iscatalytically

active in its acidicform

Glucose-6-phosphate Isomerase