CAP-11-Aldehydes and Ketones II [Modo de Compatibilidade]

(Parte 1 de 2)

Chapter 1

Aldehydes and Ketones I. Aldol Reactions

The Acidity of the α αα αHydrogens of Carbonyl

Compounds: Enolate Anions

Hydrogens on carbons α αα αto carbonyls are unusually acidic

The resulting anion is stabilized by resonance to the carbonyl

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

The enolate anion can be protonated at the carbon or the oxygen

The resultant enol and keto forms of the carbonyl are formed reversibly and are interconvertible

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Keto and Enol Tautomers

Enol-keto tautomers are constitutional isomers that are easily interconverted by a trace of acid or base

Most aldehydes and ketones exist primarily in the keto form because of the greater strength of the carbon-oxygen double bond relative to the carbon-carbon double bond

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

β ββ β-Dicarbonyl compounds exist primarily in the enol form

The enol is more stable because it has a conjugated pi pipi pisystem and because of stabilization of the enol through hydrogen bonding

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Reactions via Enols and Enolate Anions

Race mization

An optically active aldehyde or ketone with a stereocenter at the α αα α-carbon can racemize in the presence of catalytic acid or base

The intermediate enol or enolate has no stereocenter at the α αα α position

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

The mechanisms of base and acid catalysed racemization are shown below

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Halogenation of Ketones

Ketones can be halogenated at the α αα αposition in the presence of acid or base and X 2

Base-promoted halogenation occurs via an enolate

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Acid-catalyzed halogenation proceeds via the enol 9

Haloform Reaction

Reaction of methyl ketones with X2 in the presence of base results in multiple halogenation at the methyl carbon

»Insert mechanism page 7

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

When methyl ketones react with X2 in aqueous hydroxide the reaction gives a carboxylate anion and a haloform (CX3 H)

The trihalomethyl anion is a relatively good leaving group because the negative charge is stabilized by the three halogen atoms

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

The Aldol Reaction: The Addition of Enolate

Anions to Aldehydes and Ketones

Acetaldehyde dimerizes in the presence of dilute sodium hydroxide at room temperature

The product is called an aldol because it is both an ald ehyde and an alcohol

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

The mechanism proceeds through the enolate anion 13

Dehydration of the Aldol Product

If the aldol reaction mixture is heated, dehydration to an α αα α, β ββ β- unsaturated carbonyl compound takes place

Dehydration is favorable because the product is stabilized by conjugation of the alkene with the carbonyl group

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

In some aldol reactions, the aldol product cannot be isolated because it is rapidly dehydrated to the α αα α, β ββ β-unsaturated compound

Synthetic Applications

The aldol reaction links two smaller molecules and creates a new carbon-carbon bond

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Aldol reactions with ketones are generally unfavorable because the equilibrium favors the starting ketone

The use of a special apparatus which removes product from the reaction mixture allows isolation of a good yield of the aldol product of acetone

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

The Reversibility of Aldol Additions

Aldol addition products undergo retro-aldolreactions in the presence of strong base

Acid-Catalyzed Aldol Condensation This reaction generally leads directly to the dehydration product

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Crossed Aldol Reactions

Crossed aldol reactions (aldol reactions involving two different aldehydes) are of little use when they lead to a mixture of products

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Practical Crossed Aldol Reactions

Crossed aldol reactions give one predictable product when one of the reaction partners has no α αα α hydrogens

The carbonyl compound withoutany α αα αhydrogens is put in basic solution, and the carbonyl withone or two α αα αhydrogens is added slowly

Dehydration usually occurs immediately, especially if an extended conjugated system results

Química Orgânica B -Síntese de Aldeídos e Cetonas

Prof. Dr. Sandro Rogério Giacomelli

Claisen- Schmidt Reactions

(Parte 1 de 2)