Chapter 16: Aldehydes and Ketones

Lecture 20 Chem 30B

Oxidation of Aldehydes
Aldehydes are oxidized to carboxylic acids by a variety of oxidizing agents, including H2CrO4.
CHO Hexanal H2 Cr O4 COOH Hexanoic acid

They are also oxidized by Ag+.

O CH + A g2 O HO Vanillin O COH + Ag HO Vanillic acid

CH3 O

T HF, H 2 O N aOH

HCl H2 O

CH3 O

Oxidation of Aldehydes
Aldehydes are oxidized by O2 in a radical chain reaction. Liquid aldehydes are so sensitive to air that they must be stored under N2.

O 2 CH Benzaldehyde + O2 2

O COH Benzoic acid

Oxidation of Ketones
Ketones are not normally oxidized by chromic acid. They are oxidized by powerful oxidants at high temperature and high concentrations of acid or base.
O OH HN O 3 HO Cyclohexanone (k e to form) Cyclohexanone (e nol form) O OH O Hexanedioic acid (Adipic acid)

Reduction
Aldehydes can be reduced to 1 alcohols. Ketones can be reduced to 2 alcohols. The C=O group of an aldehyde or ketone can be reduced to a -CH2- group.
Aldehydes O RCH RCH3 Can Be Reduced to RCH2 OH Ketones O RCR' RCH2 R' Can Be Reduced to OH RCHR'

Metal Hydride Reduction

The most common laboratory reagents for the reduction of aldehydes and ketones are NaBH4 and LiAlH4.
Both reagents are sources of hydride ion, H:-, a very powerful nucleophile.
H Na
+

H Li
+

H- B- H

H- A l- H

H: Hydride ion

H Sodium borohydride

H Lithium aluminum hydride (LAH)

NaBH4 Reduction
Reductions with NaBH4 are most commonly carried out in aqueous methanol, in pure methanol, or in ethanol. One mole of NaBH4 reduces four moles of aldehyde or ketone.
O 4 RCH + NaBH4 methanol ( RCH2 O) 4 B Na A tetraalkyl borate
+

H2 O

4 RCH2 OH + borate salts

NaBH4 Reduction
The key step in metal hydride reduction is transfer of a hydride ion to carbon of the C=O group to form a tetrahedral carbonyl addition compound.
This H comes from w ater du rin g hydrolys is H H O O BH3 Na R-C-R' H
+

+ Na H-B-H + R-C-R'

H2 O

O-H R-C-R' H

This H comes from the hydride reducing agen t

LiAlH4 Reduction
Unlike NaBH4, LiAlH4 reacts violently with water, methanol, and other protic solvents. Reductions using it are carried out in diethyl ether or tetrahydrofuran (THF).
O ether + LiAlH4 4 RCR H2 O - + ( R2 CHO) 4 Al Li H+ or OHA tetraalk yl alu min ate OH 4 RCHR + aluminum salts

Catalytic Reduction
Catalytic reductions are generally carried out at from 25 to 100C and 1 to 5 atm H2.

O + Cyclohe xanone H2 Pt 25 o C, 2 atm

OH

Cyclohe xanol

Catalytic Reduction
A carbon-carbon double bond may also be reduced under O these conditions.
2 H2 H Ni trans- 2-Butenal (Crotonalde hyde) OH 1-Butanol

Catalytic Reduction
By careful choice of experimental conditions, it is often possible to selectively reduce a carbon-carbon double in the presence of an aldehyde or ketone.

O 1 . NaBH4 RCH=CHCR' 2 . H2 O
O RCH=CHCR' + H2 Rh

OH RCH=CHCHR'
O RCH2 CH 2 CR'

Clemmensen Reduction
Refluxing an aldehyde or ketone with amalgamated zinc in concentrated HCl converts the carbonyl group to a methylene group.

OH O Zn( Hg) , HCl

OH

Wolff-Kishner Reduction
In the original procedure, the aldehyde or ketone and hydrazine are refluxed with KOH in a highboiling solvent. The same reaction can be brought about using hydrazine and potassium tert-butoxide in DMSO.
O + H2 NN H2 Hydrazine KOH diethylen e glycol (reflux)

+ N 2 + H2 O

Racemization
Racemization at an -carbon may be catalyzed by either acid or base.
O OH Ph An achiral enol O

Ph (R)-3-Phenyl-2b utanone

Ph (S)-3-Phenyl-2butan one

Deuterium Exchange
Deuterium exchange at an -carbon may be catalyzed by either acid or base.
O CH 3 CCH 3 Acetone + 6 D2 O D
+ -

or OD

O CD 3 CCD 3 + 6 HOD Acetone-d 6

-Halogenation
-Halogenation: aldehydes and ketones with at least one -hydrogen react at an -carbon with Br2 and Cl2 .
O + Br2 Acetop henone CH 3 COOH -Bromoacetoph enone O Br + HBr

Reaction is catalyzed by both acid and base.

-Halogenation
Acid-catalyzed -halogenation
Step 1: Acid-catalyzed enolization.

OH R'-C-C-R R

slow

H-O C R' C

R R

Step 2: Nucleophilic attack of the enol on halogen.

H-O C R' C

R + Br R Br fast

H O R'

Br C C R R + Br:
-

Step 3: (not shown) Proton transfer to solvent completes the reaction.

-Halogenation
Base-promoted -halogenation
Step 1: Formation of an enolate anion.
OH R'-C-C-R + - :OH R slow O C - R C O: C C R + H2 O

R' R R' R Res on ance-stab ilized enolate anion

Step 2: Nucleophilic attack of the enolate anion on halogen.

O: C R' C R R + Br Br fast R' O C Br C R + R Br

-Halogenation
Acid-catalyzed halogenation:
Introduction of a second halogen is slower than the first. Introduction of the electronegative halogen on the carbon decreases the basicity of the carbonyl oxygen toward protonation.

Base-promoted -halogenation:
Each successive halogenation is more rapid than the previous one. The introduction of the electronegative halogen on the carbon increases the acidity of the remaining hydrogens and, thus, each successive -hydrogen is removed more rapidly than the previous one.