Reacções Aldol: Formação de Enolatos e Enolatos Aniônicos em Química Orgânica, Notas de estudo de Química Industrial

Baixe Reacções Aldol: Formação de Enolatos e Enolatos Aniônicos em Química Orgânica e outras Notas de estudo em PDF para Química Industrial, somente na Docsity! Chapter 11 Aldehydes and Ketones II. Aldol Reactions 1
The Acidity of the α Hydrogens of Carbonyl Compounds: Enolate Anions Hydrogens on carbons α to 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 2 β-Dicarbonyl compounds exist primarily in the enol form  The enol is more stable because it has a conjugated π system and because of stabilization of the enol through hydrogen bonding Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 5
Reactions via Enols and Enolate Anions  Racemization An optically active aldehyde or ketone with a stereocenter at the α-carbon can racemize in the presence of catalytic acid or base  The intermediate enol or enolate has no stereocenter at the α position Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 6 The mechanisms of base and acid catalysed racemization are shown below Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 7  Haloform Reaction Reaction of methyl ketones with X2 in the presence of base results in multiple halogenation at the methyl carbon » Insert mechanism page 777 Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 10 When methyl ketones react with X2 in aqueous hydroxide the reaction gives a carboxylate anion and a haloform (CX3H)  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 11
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 aldehyde and an alcohol Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 12  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 15 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 16  The Reversibility of Aldol Additions Aldol addition products undergo retro-aldol reactions 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 17  Claisen-Schmidt Reactions Crossed-aldol reactions in which one partner is a ketone are called Claisen-Schmidt reactions  The product of ketone self-condensation is not obtained because the equilibrium is not favorable Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 20 Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 21  Condensation with Nitroalkanes The α hydrogens of nitroalkanes are weakly acidic (pKa = 10) because the resulting anion is resonance stabilized Nitroalkane anions can undergo aldol-like condensation with aldehydes and ketones Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 22  The nitro group can be easily reduced to an amine  Regioselective Formation of Enolate Anions Unsymmetrical ketones can form two different enolates The thermodynamic enolate is the most stable enolate i.e. the one with the more highly substituted double bond  A weak base favors the thermodynamic enolate because an equilibrium between the enolates is estabilished Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 25 The kinetic enolate is the enolate formed fastest and it usually is the enolate with the least substituted double bond  A strong, sterically hindered base such as lithium diisopropyl amide favors formation of the kinetic enolate  Lithium Enolates in Directed Aldol Reactions Crossed aldol reactions proceed effectively when a ketone is first deprotonated with a strong base such as LDA and the aldehyde is added slowly to the enolate Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 26 An unsymmetrical ketone can be selectively deprotonated with LDA to form the kinetic enolate and this will react with an aldehyde to give primarily one product Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 27 The α-selenyl ketone is converted to the α,β-unsaturated carbonyl compound by reaction with hydrogen peroxide  Elimination of the selenoxide produces the unsaturated carbonyl Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 30
Additions to α,β-Unsaturated Aldehydes and Ketones α,β-Unsaturated aldehydes and ketones can react by simple (1,2) or conjugate (1,4) addition  Both the carbonyl carbon and the β carbon are electrophilic and can react with nucleophiles Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 31 Stronger nucleophiles such as Grignard reagents favor 1,2 addition whereas weaker nucleophiles such as cyanide or amines favor 1,4 addition Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 32  Michael Additions Addition of an enolate to an α,β-unsaturated carbonyl compound usually occurs by conjugate addition This reaction is called a Michael addition Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 35 A Robinson annulation can be used to build a new six-membered ring on an existing ring  Robinson annulation involves a Michael addition followed by an aldol condensation to close the ring Química Orgânica B - Síntese de Aldeídos e Cetonas Prof. Dr. Sandro Rogério Giacomelli 36