Organic Chemistry Lecture Outline Chapter 23: Carbonyl Condensation Reactions

I. CARBONYL CONDENSATION REACTIONS Carbonyl condensation reactions occur between an enolate or enol generated from a carbonyl compound attacks the electrophilic carbon of a second carbonyl group (of the same type of molecule or other type). A β-hydroxycarbonyl product is formed which may undergo elimination to give an α, β− unsaturated carbonyl product.

A. The Aldol Condensation Acid Catalyzed

H

H

O

R

H+

H

H

O

R

H

H R

OH

Enol

H

O

R

H

OHHR

Base-Catalyzed

H

H

O

R

B

H

O

RH

O

R

Resonance Stabilized Enolate

H R

O

H

O

R

H

R O

H-OH

H

O

R

H

R OH

1. In a simple aldol condensation reaction occurs two molecules of an aldehyde react with each other. The reaction is

usually either acid or base-catalyzed. 2. One of the aldehyde molecules behaves as a nuleophile and the other aldehyde behaves as an electrophile. 3. The enol or enolate form of one aldehyde (the nucleophile) attacks the carbonyl carbon atom of the other aldehyde (the

electrophile) 4. The ß-hydroxyaldehyde which results after the aldol condensation often undergoes dehydration to form an α,ß-

unsaturated aldehyde.

H

O

R

H

R OH

H

B:

H

O

R

H R

β-hydroxycarbonyl α,β-unsaturated carbonyl

Organic Chemistry Lecture Outline Chapter 23: Carbonyl Condensation Reactions

B. Condensation of Ketones 1. Condensation between two ketones occurs under acid or base catalysis. 2. Symmetrical ketones (like acetone) provide a single aldol product. 3. Unsymmetrical ketones results in mixtures of products since more than one enol or enolate can be generated. C. Crossed or Mixed Aldol Condensation

H

CH3

O

B

HH

Acetone

CH3

O

HH

Enolate derived from acetone

H

O

CH3

O

HH

O

H

CH3

O

HH

HO

H

β−Hydroxyketone

1. Crossed aldol condensations occur between different aldehydes or ketones. a. Crossed condensations can occur between two different aldehydes. b. Crossed condensations can occur between two different ketones. c. Crossed condensations can occur between an aldehyde and a ketone. The aldehyde usually behaves as the

electrophile unless the ketone cannot be enolized. 2. Complex mixtures of products often result in crossed condensation reactions. D. Intramolecular Aldol Condensation

O

O

HO

O

H

HO

O

H H

O

H

1. Intramolecular aldol condensation occurs between two carbonyl groups in the same molecule to generate a cyclic product.

2. Dehydration usually occurs to give the ,ß-unsaturated product. 3. Usually five- and six-membered rings are formed. Very small rings may not form due to strain energy and entropy

may prevent very large ring formation.

Organic Chemistry Lecture Outline Chapter 23: Carbonyl Condensation Reactions

E. Claisen Condensation

H

OR'

O

R

B

OR'

O

ROR'

O

R

Resonance Stabilized Enolate

OR' R

O

H

O

R

OR'

R O

OR'

O

R

R O

+ HOR"

1. The Claisen condensation is a condensation reaction between two molecules of the same ester. The reaction is usually

base catalyzed. 2. The reaction mechanism of the Claisen condensation is analogous to the aldol condensation. 3. A ß-ketoester product results from a Claisen condensation. F. Crossed Claisen Condensation 1. A crossed Claisen condensation occurs between two different esters. 2. As in crossed aldol condensations, complex product mixtures result. G. Diekmann Cyclization

H3CO

O

O

OCH3

H3CO

O

O

H3CO

O

H3CO

O

+ H3C OH

1. The Diekmann cyclization is a intramolecular Claien condensation II. CONJUGATE ADDITIONS WITH ENOLS AND ENOLATES TO α, β-UNSATURATED CARBONYLS (MICHAEL ADDITION) A. CONJUGATE ADDITION OF ENOLS AND ENOLATES 1. Enols and enolates are nucleophiles that react with α,β-unsaturated carbonyls at the number "4" carbon. 2. The reaction between enols or enolats and α,β-unsaturated carbonyls is referred to as a Michael addition.

O

O

H

enolate

α,β-unsaturated carbonyl

O

O

H

E+

O

O

H

E