Chapter 13 Reactions at the alpha-Carbon of carbonyl compounds

13.1 The acidity of an alpha hydrogen

The alpha hydrogen of a ketone or an aldehyde is ______ (more/less) acidic than the alpha hydrogen of an ester

more

13.1 The acidity of an alpha hydrogen

The pKa value for dissociation of a proton from the alpha carbon of an aldehyde or a ketone ranges from ______, and the pKa value for dissociation of a proton attached to the alpha carbon of an ester is about ___

16-20, 25

13.1 The acidity of an alpha hydrogen

Notice that although the alpha hydrogen is more acidic that most other carbon-bound hydrogens, it is _____ (more/less) acidic than a hydrogen of water

less

13.1 The acidity of an alpha hydrogen

A hydrogen bonded to an alpha carbon is more acidic than hydrogens bonded to other sp3 carbons because the base formed when a proton is removed from an alpha carbon is relatively stable. As we know, the more stable the base, the _____ (weaker/stronger) its conjugate acid

stronger

13.1 The acidity of an alpha hydrogen

Why are aldehydes and ketones more acidic than esters?

The electrons left behind when a proton is removed from the alpha carbon of an ester are not as readily delocalized onto the carbonyl ______ as they would be in an aldehyde or a ketone.

oxygen

13.2 Keto-Enol Tautomers

Keto-enol tautomers differ in the location of a double bond and a _____

hydrogen

13.2 Keto-Enol Tautomers

For most ketones, which tautomer is less stable?

enol

13.2 Keto-Enol Tautomers

Phenol is unique in that its enol tautomer is more stable than its keto tautomer. What characteristic is responsible for the stability?

aromaticity

13.3 Keto-Enol Interconversion

Mechanism for Base catalyzed keto-enol interconversion

(Hydroxide ion removes proton from the alpha carbon of the keto tautomer, forming an anion called an enolate ion. The enolate ion has 2 resonance contributors. Protonating the oxygen forms the enol tautomer)

13.3 Keto-Enol Interconversion

Mechanism for acid catalyzed keto-enol interconversion

13.4 Alkylation of Enolate Ions

13.3 Keto-Enol Interconversion

The steps are reversed in the base and acid catalyzed interconversions.

Acid or base catalyzed reaction?

Step 1: The base removes a proton from the alpha-carbon

Step 2. The oxygen is protonated

base

13.3 Keto-Enol Interconversion

Acid or base catalyzed reaction?

Step 1: the oxygen is protonated

Step 2: proton is removed from the alpha carbon

acid

13.4 Alkylation of Enolate Ions

Alkylation of the alpha carbon of a carbonyl compound is an important reaction because it gives us another way to form a ______ bond

carbon-carbon

13.4 Alkylation of Enolate Ions

Alkylation is carried out by first removing a ______ from the alpha carbon with a base and then adding the appropriate alkyl halide

proton

13.4 Alkylation of Enolate Ions

Alkylation is an _______ reaction, so it works best with primary alkyl halides and methyl halides

SN2

13.4 Alkylation of Enolate Ions

If the ketones is unsymmetrical and has hydrogens on both alpha carbons, ____ monoalkylated products can be obtained because either alpha carbon can be alkylated

2

13.4 Alkylation of Enolate Ions

The kinetic product is the faster formed product. The thermodynamic product is the _____ (more/less) stable product

more

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

We have just seen that a proton can be removed from the alpha-carbon of an aldehyde or a ketone, converting the alpha carbon into a _____

nucleophile

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

An aldol addition. One molecule of a carbonyl compound, after a proton is removed from an alpha carbon, reacts as a _______ and adds to the ______ carbonyl carbon of a 2nd molecule of the carbonyl compound

nucleophile, electrophilic

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

An aldol addition is a reaction between 2 molecules of a/n _______ or 2 molecules of a/n ____

aldehyde, ketone

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

Aldol addition: This reaction forms a new C-C bond that connects the alpha carbon of one molecule and the Carbon that was originally the carbonyl carbon of the other molecule

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

Mechanism for Aldol Addition screenshot

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

The aldol addition is what kind of reaction?

nucleophilic addition

13.5 An Aldol Addition forms beta-hydroxyaldehydes or beta-hydroxyketones

Because an aldol addition is _______, when the product of an aldol addition (beta hydroxyaldehyde or beta-hydroxyketone)is heated with a hydroxide ion and water, the aldehyde or ketone that formed the aldol addition product can be regenerated

reversible

13.6 The Dehydration of Aldol Addition Products Forms alpha, beta-unsaturated aldehydes and ketones

Remember that alcohols dehydrate when heated with _____

acid

13.6 The Dehydration of Aldol Addition Products Forms alpha, beta-unsaturated aldehydes and ketones

The Beta-hydroxyaldehyde and Beta-hydroxyketone products of aldol addition reactions are easier to dehydrate than many other alcohols, because the double bond formed when the compound is dehydrated is _________ with a carbonyl group.

This characteristic increases the stability of the product and thus makes it easier to form

conjugation

13.6 The Dehydration of Aldol Addition Products Forms alpha, beta-unsaturated aldehydes and ketones

An aldol addition product loses _______ to form an aldol condensation product

water

13.6 The Dehydration of Aldol Addition Products Forms alpha, beta-unsaturated aldehydes and ketones

Unlike alcohols that can only be dehydrated under acidic conditions, Beta-hydroxyaldehydes and beta-hydroxyketones can be dehydrated under ______ conditions if the rxn is carried out with excess hydroxide ion

basic

13.6 The Dehydration of Aldol Addition Products Forms alpha, beta-unsaturated aldehydes and ketones

Reaction screenshot

13.8 A Claisen Condensation forms a β-Keto Ester

When 2 molecules of an ______ undergo a condensation reaction, it is called a Claisen condensation

esters

13.8 A Claisen Condensation forms a β-Keto Ester

Mechanism for Claisen Condition

13.8 A Claisen Condensation forms a β-Keto Ester

The Claisen condensation is what kind of reaction?

nucleophilic acyl substitution

13.8 A Claisen Condensation forms a β-Keto Ester

In the Claisen condensation, the negatively charged oxygen re-forms the carbon-oxygen pi bond and eliminates the -OR group. In the aldol addition, the negatively charged oxygen obtains a _____ from the solvent

proton

13.8 A Claisen Condensation forms a β-Keto Ester

What kind of reaction is the Claisen condensation reaction?

What kind of reaction is the aldol addition?

nucleophilic acyl substitution, nucleophilic addition

13.9 CO2 can be removed from a carboxylic acid with a carbonyl group at the 3 position

Decarboxylation is the loss of CO2 from a molecule and can occur if the CO2 group is attached the carbonyl group. What characteristic of carbanion is responsible for this phenomenon?

poor leaving group (strong base)

13.9 CO2 can be removed from a carboxylic acid with a carbonyl group at the 3 position

In summary, carboxylic acids with a carbonyl group at the 3 position lose CO2 when they are heated.

Summary points

A hydrogen bonded to an α-carbon of an aldehyde, ketone, or ester is sufficiently acidic to be removed by a _______ (weak/strong) base

strong

Summary points

Aldehydes and ketones (pKa 16-20) are _____ (more/less) acidic than esters (pKa 25). A hydrogen bonded to an α carbon flanked by 2 carbonyl groups is even____ (more/less) acidic (pKa 9-11)

more, more

Summary points

Keto-enol interconversion can be catalyzed by acids or bases. Which tautomer is more stable, keto or enol?

keto

Summary points

What reaction?

, the enolate ion of an aldehyde or a ketone reacts with the carbonyl carbon of a second molecule of aldehyde or ketone, forming a β-hydroxyaldehyde or β-hydroxyketone. The new C-C bonds forms between the alpha carbon of one molecule and the carbon that formerly was the carbonyl carbon of the other molecule

Chap 13 Summary Reactions

Rxn 1 Keto-enol interconversion (13.3 p 465)

Chap 13 Summary Reactions

Rxn 2 Alkylating the alpha carbon of carbonyl compounds (13.4 p 467)

Chap 13 Summary Reactions

Rxn 3 An aldol addition of 2 aldehydes, 2 ketones, or an aldehyde and a ketone (13.5 p 469)

Chap 13 Summary Reactions

Rxn 4 An aldol condensation is an aldol addition followed by acid-catalyzed or base-catalyzed dehydration (13.6) p 470

Chapter 13 Reactions

Rxn 5 Claisen condensation of 2 esters (13.8 p 473)

Chapter 13 Reactions

Rxn 7 Decarboxylation of 3-oxocarboxylic acids (13.9 p. 475)