Lecture 19- Aldehydes And Ketones

General

Organic Chemistry Two credits Second Semester 2009

King Saud bin Abdulaziz University for Health Science

Reference Book: Organic Chemistry: A Brief Course, by Robert C. Atkins and Francis A. Carey Third Edition

Instructor: Rabih O. Al-Kaysi, PhD.

Lecture 19

Chapter 11

Aldehydes and Ketones

Some reactions of aldehydes and ketones progress beyond the nucleophilic addition stage

Acetal formation Imine formation Compounds related to imines Enamines The Wittig reaction

Reaction with Primary Amines: Imines

Imine (Schiff's Base) Formation

H2N ••

+

C

O •• ••

••

HN

C

••

O ••

R

R

a carbinolamine ••

N R

C

(imine)

+ H2O

H

Example O CH + CH3NH2

CH=NCH3 + H2O N-Benzylidenemethylamine (70%)

Example O CH + CH3NH2

OH CH NHCH3

CH=NCH3 + H2O N-Benzylidenemethylamine (70%)

Example

O + (CH3)2CHCH2NH2

NCH2CH(CH3)2

+ H2O

N-Cyclohexylideneisobutylamine (79%)

Example

O + (CH3)2CHCH2NH2 OH NHCH2CH(CH3)2 NCH2CH(CH3)2

+ H2O

N-Cyclohexylideneisobutylamine (79%)

Terminology Terminology

O CH3CH2CH2CH γ β α The reference atom is the carbonyl carbon. Other carbons are designated α , β , γ , etc. on the basis of their position with respect to the carbonyl carbon. Hydrogens take the same Greek letter as the carbon to which they are attached.

Enol Content Enol Content

O R2CHCR'

OH R2C

keto

CR'

enol

percent enol is usually very small keto form usually 45-60 kJ/mol more stable than enol

Enol Content Enol Content

O CH3CH

OH H2C

O CH3CCH3

CH

K = 3 x 10-7

OH H2C

CCH3

K = 6 x 10-9

1,3-Diketones 1,3-Diketones (also called β -diketones) (also called β -diketones)

Example: 2,4-pentanedione O

O

CH3CCH2CCH3 (20%)

O

OH CH3C

CHCCH3

(80%)

keto form is less stable than enol form

Base-Catalyzed Enolization: Enolate Anions

Acidity of α -Hydrogen Acidity of α -Hydrogen

•• O ••

•• • O•

R2C

CR'

– R2C ••

CR'

+ H+

H

pKa = 16-20

Just for general knowledge, will not be tested on

Acidity of α -Hydrogen Acidity of α -Hydrogen

•• O ••

•• • O•

R2C

CR'

– R2C ••

CR'

+ H+

H

•• •• O ••–

pKa = 16-20 R2C

CR'

Just for general knowledge, will not be tested on

Acidity of α -Hydrogen Acidity of α -Hydrogen

•• O ••

•• • O•

R2C

CR'

– R2C

••

CR'

+ H+

H enolate ion •• •• O ••–

pKa = 16-20 R2C

CR'

Just for general knowledge, will not be tested on

Mechanism of Enolization Mechanism of Enolization (Base-catalyzed) (Base-catalyzed)

•• • O•

–

– •• •• O ••

R2C

CR'

H

H

Just for general knowledge, will not be tested on

Mechanism of Enolization Mechanism of Enolization (Base-catalyzed) (Base-catalyzed)

– •• •• O •• R2C •• •• O

CR'

H

H

Just for general knowledge, will not be tested on

Mechanism of Enolization Mechanism of Enolization (Base-catalyzed) (Base-catalyzed)

– •• •• O •• R2C

H H

O •• ••

CR'

Just for general knowledge, will not be tested on

Mechanism of Enolization Mechanism of Enolization (Base-catalyzed) (Base-catalyzed)

– •• •• O •• R2C

H H

O •• ••

CR'

Just for general knowledge, will not be tested on

Mechanism of Enolization Mechanism of Enolization (Base-catalyzed) (Base-catalyzed)

•• •• O

R2C

H

H

– •• O •• ••

CR'

Just for general knowledge, will not be tested on

Acidity of α -Hydrogen Acidity of α -Hydrogen

O (CH3)2CHCH

pKa = 15.5

O CCH3

pKa = 15.8

β -Diketones are much more acidic β -Diketones are much more acidic

O

O

CH3CCH2CCH3

pKa = 9

β -Diketones are much more acidic β -Diketones are much more acidic

H3C

O

O

C

C

C

CH3

H

H

Ka = 10–9 O H3C

C

O – •• C H

C

CH3

+ H+

The Aldol Condensation Gives β -hydroxy aldehydes or ketones

Some thoughts... Some thoughts...

O

O

–• •• RCH2CH + • OH ••

pKa = 16-20

••

RCHCH + HOH •• •• – pKa = 16

A basic solution contains significant amounts of the aldehyde and its enolate. Aldehydes undergo nucleophilic addition. Enolate ions are nucleophiles. What about nucleophilic addition of enolate to aldehyde?

•• • O•

– RCHCH ••

RCH2CH O •• ••

•• • O•

– RCHCH ••

•• • O•

RCHCH

•• • O•

RCHCH

RCH2CH

RCH2CH

RCH2CH

O ••

•• O •• •• –

•• OH ••

••

•• • O•

•• • O•

– RCHCH ••

•• • O•

RCHCH

RCHCH

RCH2CH

RCH2CH

RCH2CH

O ••

•• O •• •• –

•• OH ••

••

O 2RCH2CH

O NaOH

RCH2CH OH

CHCH R

Aldol Addition Aldol Addition

O RCH2CH OH

CHCH R

product is called an "aldol" because it is both an aldehyde and an alcohol

Aldol Addition of Acetaldehyde Aldol Addition of Acetaldehyde

O 2CH3CH

NaOH, H2O 5°C

O CH3CH

CH2CH

OH Acetaldol (50%)

Aldol Addition of Butanal Aldol Addition of Butanal

O 2CH3CH2CH2CH KOH, H2O

6°C O

CH3CH2CH2CH OH (75%)

CHCH CH2CH3

Aldol Condensation Aldol Condensation

O 2RCH2CH

O NaOH

RCH2CH OH

CHCH R

Aldol Condensation of Butanal Aldol Condensation of Butanal

O 2CH3CH2CH2CH NaOH, H2O

80-100°C

Aldol Condensation of Butanal Aldol Condensation of Butanal

O 2CH3CH2CH2CH NaOH, H2O

80-100°C O

CH3CH2CH2CH

CCH CH2CH3

(86%)

Aldol reactions of ketones Aldol reactions of ketones

O 2CH3CCH3

2% 98%

OH

O

CH3CCH2CCH3 CH3

the equilibrium constant for aldol addition reactions of ketones is usually unfavorable

Alkylation of Enolate Anions

Enolate Ions in SN2 Reactions Enolate Ions in SN2 Reactions

Enolate ions are nucleophiles and react with alkyl halides. However, alkylation of simple enolates does not work well. Enolates derived from β -diketones can be alkylated efficiently.

Example Example

O

O

CH3CCH2CCH3

+ CH3I

K2CO3

O

O

CH3CCHCCH3 CH3 (75-77%)