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ORGANIC - MCMURRY 9E

CH. 23 - CARBONYL CONDENSATIONS

CONCEPT: CONDENSATION REACTIONS

A condensation reaction spontaneously combines two or more molecules with the loss of a smaller molecule.

● Instead of just reacting with electophiles, enolates are able to react with themselves to self-condensate

● Obviously, ___________________________ are required for this type of reaction to take place

Example Reactions:



CONCEPT: ALDOL CONDENSATION

Via enolates, ketones and aldehydes will react with ___________________ to condensate into ______________

● The final products are called “aldols” because they are part ________________ and part __________________

Mechanism:

1. Form the enolate

2. Nucleophilic attack the other carbonyl (which we will call the electrophile)

3. Protonate the tetrahedral intermediate:

β-hydroxy carbonyls are ______________ to dehydrate than typical alcohols due to __________________________

Many times, we will simply assume that the condensation product dehydrated on its own, without requiring an explanation.



PRACTICE: What product can be isolated from the following aldol condensation reaction?

O

OH –



PRACTICE: Provide the mechanism for the following transformation.

O OH

H

OH – O



CONCEPT: CROSSED ALDOL

When we run condensation reactions on two different ketones or aldehydes, mixed products are difficult to avoid.

In general, condensation reactions with two different carbonyls work best when one carbonyl is nonenolizable.

Nonenolizable Carbonyls:



PRACTICE: Give the structure of the aldehydes or ketones used to create the product prepared by a crossed aldol condensation reaction.

PRACTICE: Give the structure of the aldehydes or ketones used to create the product prepared by a crossed aldol reaction.

O OH

PRACTICE: What product can be isolated from the following aldol condensation reaction?

OH –O O O

H



CONCEPT: CLAISEN-SCHMIDT REACTION

When a crossed aldol contains an enolizable aldehyde and a ketone, one product does predominate.

● Aldehydes are more susceptible toward nucleophilic addition than ketones, favoring a single enolate.

EXAMPLE: Predict the major product of the following condensation.



CONCEPT: CLAISEN CONDENSATION

Via enolates, esters will react with _________________ to condensate into ________________________

Mechanism:

1. Form the enolate

2. Nucleophilic attack the other carbonyl (which we will call the electrophile)

3. Kick out the good leaving group:

Example Application:



PRACTICE: Draw the structure of the Claisen condensation product for each of the following compounds.

O

OEt

O

OEt

NaOEt

EtOH

PRACTICE: Draw the structure of the Claisen condensation product for each of the following compounds.

O

O

O

O

NaOMe

MeOH

PRACTICE: Give the structure of the ester precursor for the following Claisen condensation product.



CONCEPT: INTRAMOLECULAR CONDENSATION

Dicarbonyl compounds have the ability to self-condensate through cyclization if it will generate a ___ or ___-membered ring.

● When a diketone or dialdehyde self-condensate, the resulting product is called a cyclic enone

● When a diester self-condensates, the resulting product is called a cyclic β-ketoester

□ This is known as a Dieckmann Condensation



PRACTICE: Consider the following reaction. Provide a stepwise mechanism to explain the given transformation.



CONCEPT: CONJUGATE ADDITION OF ENONES

Once an aldol condensation is completed, an electrophilic carbonyl still remains.

● Enones remain susceptible to nucleophilic attack, however they now have two electrophilic regions:

● Also known as 1,2 vs. 1,4 addition of enones, or nucleophilic addition vs. conjugate addition of carbonyls.

Nucleophilic Addition vs. Conjugate Addition



CONCEPT: THE MICHAEL REACTION

The Michael Reaction is a 1,4-conjugate addition of an enone with an enolate.

● Basically _____________________

● Always forms 1,5-dicarbonyls

Mechanism:



PRACTICE: Determine the product in the following conjugated addition reaction.





CONCEPT: ENAMINE ALKYLATION AND ACYLATION

Carbonyls easily react with acid-catalyzed amine solvents to form imines and enamines.

Secondary Amine Addition: Enamines

Enamines have the ability to alkylate or acylate via the formation of an iminium salt

EXAMPLE: Predict the products of the following reactions

1.



PRACTICE: Provide the major product after each step for the following reaction.

OHN

H+

Br

Acetone

H3O+

PRACTICE: Which of the following can NOT be formed through the stork enamine reaction with 2-butanone?

a) 3-pentanone

b) 3-methyl-2-butanone

c) 2-octanone

d) 3-octanone



CONCEPT: ROBINSON ANNULATION

1,5-dicarbonyl compounds have the ability to undergo intramolecular self-condensation into 6-membered enones.

● When the 1,5-dicarbonyl is generated via Michael Reaction (enone + enolate), it is called a Robinson Annulation

` ●Basically _____________________

EXAMPLE: Predict the major product of the following Robinson Annulation.



PRACTICE: Provide the product for the following Robinson Annulation Reaction.

O OO

PRACTICE: How would you prepare the following compound using a Robinson annulation reaction between a di-ketone and an alpha, beta unsaturated ketone?

O

O

PRACTICE: How would you prepare the following compound using a Robinson annulation reaction between a ketone and an alpha, beta unsaturated ketone?

O



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