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Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 18
Carbonyl
Compounds II
Radicals
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall
Nomenclature of Aldehydes
If the aldehyde group is attached to a ring,
If a compound has two functional groups, the one with the
lowest priority is indicated by its prefix
Nomenclature of Ketones
If a ketone has a second functional group of higher
priority,
An aldehyde has a greater partial positive charge on its
carbonyl carbon than does a ketone
• Steric factors contribute to the reactivity of an aldehyde
• The carbonyl carbon of an aldehyde is more accessible
to the nucleophile
• Ketones have greater steric crowding in their transition
states, so they have less stable transition states
Aldehydes and ketones react with nucleophiles to form
addition products: nucleophile addition reactions
If the nucleophile that adds to the aldehyde or ketone is
an O or an N, a nucleophilic addition–elimination reaction
will occur
Formation of a New Carbon–Carbon
Bond Using Grignard Reagents
Grignard reagents react with aldehydes, ketones, and
carboxylic acid derivatives
Reaction with Acetylide Ions
In basic solution, a cyanohydrin is converted back to the
carbonyl compound
Synthesis Using Cyanohydrin
Reduction by Hydride Ion
Utilization of DIBAL to Control the
Reduction Reaction
The reduction of a carboxylic acid with LiAlH4 forms a
single primary alcohol
Acyl chloride is also reduced by LiAlH4 to yield an alcohol
An amide is reduced by LiAlH4 to an amine
Aldehydes and ketones react with a primary amine to
form an imine
This is a nucleophilic addition–elimination reaction
The pH of the reaction must be controlled
Dependence of the rate of the reaction of acetone with
hydroxylamine on the pH of the reaction: a pH rate profile
Aldehydes and ketones react with secondary amines to
form enamines
Formation of Imine Derivatives
Deoxygenation of the Carbonyl Group
Water adds to an aldehyde or ketone to form a hydrate
Why is there such a difference in the Keq values?
The equilibrium constant for the reaction depends on the
relative stabilities of the reactants and products
Addition of an Alcohol to an Aldehyde
or a Ketone
Utilization of Protecting Groups in
Synthesis
LiAlH4 will reduce the ester to yield an alcohol, but
the keto group will also be reduced
The keto group is protected as a ketal in this synthesis
The more reactive aldehyde is protected with the diol
before reaction with the Grignard reagent
• The OH group in an alcohol can be protected as a
trimethylsilyl ether
• The OH group in a carboxylic acid can be protected as
an ester
• An amino group can be protected with an acetyl group
Addition of Sulfur Nucleophiles
Desulfurization replaces the C–S bonds with C–H bonds
Formation of Alkenes
The Wittig Reaction
Preparation of the Phosphonium Ylide
If two sets of reagents are available for the synthesis of
an alkene, it is better to use the one that requires the less
sterically hindered alkyl halides
• The Wittig reaction is completely regioselective
• This reaction is the best way to make a terminal alkene
• Stable ylides form primarily E isomers, and unstabilized
ylides form primarily Z isomers
• Stable ylides have a group (C=O) that can share the
carbanion’s negative charge
Stereochemistry of Nucleophilic
Addition Reaction
• Nucleophiles that form unstable addition products form
conjugated addition products, because the conjugate
addition is not reversible
• Nucleophiles that form stable addition products can
form direct addition products or conjugate addition
products
• If the rate of direct addition is slowed down by steric
hindrance, a Grignard reagent will form the conjugate
addition product
Nucleophilic Addition to a,b-Unsaturated
Carboxylic Acid Derivatives
Enzyme-Catalyzed Additions to a,bUnsaturated Carbonyl Compounds