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Organic Chemistry

4th Edition Paula Yurkanis Bruice

Chapter 18
Carbonyl Compounds II

Irene Lee Case Western Reserve University Cleveland, OH

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

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 α,β-Unsaturated Carboxylic Acid Derivatives

Enzyme-Catalyzed Additions to α,βUnsaturated Carbonyl Compounds