Organic Chemistry 4 th Edition Paula Yurkanis Bruice Chapter 24 Catalysis Irene Lee Case Western Reserve University Cleveland, OH ©2004, Prentice Hall

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  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 ester hydrolysis Nucleophilic Catalysis

An Acid-Catalyzed Reaction A proton is donated to the reaction

The acid increases the rates of both slow steps of the reaction

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 stabilization of 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 during the 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 than water The metal ion also decreases the basicity of the leaving group

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 relative rate of B because the groups in D are less apt to adopt an unfavorable conformation for the reaction

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

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-carboxyl substituent 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 upon binding to a substrate red: before substrate-binding green: 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 the C-terminal peptide

The binding pocket at the active site of serine proteases dictates 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 the pK a 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

Glucose-6-phosphate Isomerase