CARBONYL COMPOUNDS

ALDEHYDES AND KETONES

Aldehydes and Ketones

H
R

R
C O

Aldehyde
118o

H
C O

H3C 121o

118o

C O
Ketone

H
C C

H 121o H
Resonance Structures
H
H
C O
C O
+
H3 C
H3 C

Some naturally occurring

aldehydes and ketones

Formalin, 35-40%
formadehyde in water
Preservative that reacts
with proteins causing them
to resist decay Coelacanth,
prehistoric fish

O
C

O
H
Acrolein (2-propenal)

- lachrymator and pleasant "odor"

from barbacuing meat

Preparation of Carbonyls
1. Oxidation of Alcohols
Primary alcohols can be oxidized with pyridinium chlorochromate
(PCC) to aldehydes. Ketones can be obtained from secondary
alcohols by oxidation with sodium dichromate/sulfuric acid or KMnO4.

Preparation of Carbonyls
2. Friedel Crafts Acylation
Aromatic ketones (acyl benzenes) can be produced from the reaction
of benzenoid compounds with acyl chlorides, which are derived from
carboxylic acids.

Preparation of Carbonyls
3. Ozonolysis of Alkenes
The cleavage of an alkene with ozone produces carbonyl
compounds. Recall that disubstituted double-bonded carbons
become ketones and monosubstituted double-bonded carbons
become aldehydes through ozonolysis.

Preparation of Carbonyls
4. Aldehydes from Acid Chlorides
Aldehydes are easily oxidized to carboxylic acids but carboxylic acids are
difficult to reduce to aldehydes. This difficulty is circumvented by converting
a carboxylic acid into the more reactive acid chloride, which can be readily
reduced to an aldehyde. Lithium tri-t-butoxyaluminum hydride is a mild
reducing agent that displaces chloride with hydride to produce an aldehyde.

Preparation of Carbonyls
4. Ketones from Acid Chlorides
Alkyl groups can replace the chlorine to produce ketones.

A Grignard (or organolithium) reagent would react with an acid chloride to

produce a ketone, but then the ketone would react immediately with
additional Grignard reagent in the solution to form a tertiary alcohol. This
problem is circumvented by using the weakest of the organometallic
reagents, an organocuprate, which is too weak a nucleophile to add to a
ketone.

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Reactions of Aldehydes and Ketones

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Addition to Carbonyls:
Simple Nucleophile
Carbonyls readily undergo Nucleophilic Attack

O
C +

O
C

Nuc

O H

H+

Nuc

Nuc

Alkoxide

Alcohol

Aldehyde is more reactive than ketone

O
C +
R
H

O
C +
R
R

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1. Reduction of Carbonyls
The most useful reagents for reducing aldehydes and ketones are the metal
hydride reagents.The two most common metal hydride reagents are sodium
borohydride (NaBH4) and lithium aluminum hydride (LiAlH4). These
reagents contain a polar metal-hydrogen bond that serves as a source of the
nucleophile hydride, H:-. LiAlH4 is a stronger reducing agent than NaBH4,
because the Al-H bond is more polar than the B-H bond.

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MECHANISM

LiAlH4 Reduction of RCHO and R2C=O

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2. Reaction of Carbonyls with

Cyanide Ion

The reaction is conducted using sodium cyanide at pH 10 to yield

cyanohydrin.

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Addition to Carbonyls:
Primary Amines and Alcohols
1. Addition of primary amimes

Condensation Reaction Elimination of water

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Reaction between an amine and a carbonyl compound

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General reaction

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DNP test for aldehydes & ketones gives crystalline hydrazones

NO2
O2N

H 3C
C O

H 3C

acetone

H
O2N

- H2O

N N
H

2,4-dinitrophenylhydrazine
2,4-diphenylhydrazine

H3C

NO2

C N N
H3C

hydrazone of acetone
orange crystals

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Nucleophilic Addition of Hydrazine:

The Wolff-Kishner Reduction

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Mechanism: The Wolff-Kishner Reduction

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Addition to Carbonyls:
Primary Amines and Alcohols
2. Addition of alcohols
Weak nucleophiles Acid catalyzed

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Mechanism of
hemiacetal formation

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Mechanism of acetal formation

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Addition to Carbonyls:
Carbanions
Carbanion : strong Nucleophile
- Grignard reagent : an organomagnesium bromide (RMgBr or ArMgBr).
- Organolithium compounds (RLi and ArLi)

1. Addition of Grignard reagents

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Professor Victor Grignard (1912 Nobel Prize)

Developed this chemistry with Professor P. A. Barbier

+
R C X
H
X = I or Br

Mg
Ether

H
+
R C MgX
H
Grignard Reagent

RCH2
MgX

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Grignard reagent add to carbonyls to give alcohols

MgBr

Ether

C O MgBr

H3O+

C O H
H
Benzylalcohol

C O
H

C O

1.

MgBr
C OH
Ether

2.

H3O+
Triphenylmethanol
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Nucleophilic Addition Reactions

H

O
H C H
Ph
Primary alcohols

O
C

Formaldehyde
+
Ph MgI

O
R C H
Ph
Secondary alcohols

O
C

H
Aldehydes
+
Ph MgI

H
O
R C R
Ph
tertiary alcohols

O
C

R
R
Ketone
+
Ph MgI
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2. Addition of Organolithium compounds (RLi and ArLi)

H
+
R C X
H

Li
Ether

X = I or Br

H
+
R C Li

RCH2

H
Organolithium Reagent

Li

ADDITION

C O
+
Li
+

R C O

H+
H 2O

Li

Protonation

R C O H

Alcohol

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Problems

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Problems

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Oxidation of Aldehydes
The most common oxidation reaction of carbonyl compounds is the oxidation
of aldehydes to carboxylic acids. A variety of oxidizing agents can be
used, including CrO3, Na2Cr2O7, K2Cr2O7 and KMnO4. Aldehydes are also
oxidized selectively in the presence of other functional groups using silver(I)
oxide in aqueous ammonium hydroxide. This is called Tollens reagent.
Because ketones have no H on the carbonyl carbon, they do not undergo
this oxidation reaction.

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Problems

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Reactivity of Enolate Ions

O
H
C
C

Base

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Reactivity of Enolate Ions

Reaction on carbon is more common.

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1. Haloform reaction
If excess base and halogen are used, a methyl ketone is triply halogenated
and then cleaved by base in the haloform reaction. The product are
carboxylic and haloform.

+ -CX3

+
CHX3
haloform

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2. Alkylation of Enolate Ions

ketone -hydrogen enolate ion
alkyl halide - alkylketone

O
C C
H
ketone

1) LDA, THF
2) R-X

O
C C
R
-alkylketone

LDA = lithium diisopropylamide

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3. Aldol Condensation
aldehyde ketone -hydrogen enolate ion
nucleophile aldehyde ketone
-hydroxy carbonyl aldol (aldehyde + alcohol)

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Mechanism:
Aldol Condensation

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 -hydroxy aldehyde ketone -hydrogen

, ,unsaturated aldehyde ketone
electron 4 atom

+ H2O

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Crossed Aldol Condensation

aldehyde ketone -hydrogen

-hydrogen

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Problem :

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CARBOXYLIC ACIDS

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Carboxylic Acids
pKa = 4 - 5 ,

O
C

water = 16

C
O H

H2O

H3O

Carboxylic acids are strong organic acids

O
C

O
O H

NaOH

H2O

Benzoic acid

Cl
Cl

C C
Cl

pKa =

OH
0.7

Na

Sodium Benzoate

H
Cl

C C
Cl
1.48

OH

H
Cl

2.86

H C C

C C
H

OH

H
4.76

OH
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Carboxylic Acids
Highly Polar
Low molecular weight acids show Appreciable Solubility in Water
High B.p. Extensive H-bonds to themselves and water

Ethanoic acid

Red ants
rhubarb

Vinegar

4-Bromo-2-ethylpentanoic acid

O
OH

Methanoic acid

H3C

OH

Acetic acid

O
Aspirin

OH
CH3
O
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Reactions of Carboxylic Acids

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Conversion of RCOOH to RCOCl

Carboxylic acids can't be converted to acid chlorides by using Cl- as
a nucleophile, because the attacking nucleophile Cl- is a weaker base
than the departing leaving group, -OH. But carboxylic acids can be
converted to acid chlorides using thionyl chloride, SOCl2.

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Mechanism

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Conversion of RCOOH to (RCO)2O

Carboxylic acids cannot be readily converted to anhydrides, but
dicarboxylic acid can be converted to cyclic anhydrides by heating to high
temperatures. This is a dehydration reaction because a water molecule is
lost from the diacid.

O
OH
OH

O +
O

H2O
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Conversion of RCOOH to RCOOR

Treatment of a carboxylic acid with an alcohol in the presence of an acid
catalyst forms an ester. This reaction is called a Fischer esterification.

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Mechanism
O
R

OH

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Esterification of a carboxylic acid occurs in the presence of acid

but not in the presence of base. Base removes a proton from the
carboxylic acid, forming a carboxylate anion, which does not react with
an electron-rich nucleophile.

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Intramolecular esterification of - and -hydroxy carboxylic acids

forms five- and six-lactones.

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Draw the products of each reaction

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Conversion of RCOOH to RCONR2

The direct conversion of a carboxylic acid to an amide with NH3 or an amine is
very difficult. The problem is that carboxylic acids are strong organic acids and
NH3 and amines are bases, so they undergo an acid-base reaction to form
an ammonium salt before any nucleophilic substitution occurs.

The overall conversion of RCOOH to RCONH2 requires two steps:

[1] Acid-base reaction of RCOOH with NH3 to form an ammonium salt
[2] Dehydration at high temperature (>100 oC)
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A carboxylic acid and an amine readily react to form an amide in the

presence of an additional reagent, dicyclohexylcarbodiimide (DCC), which
is converted to the by-product dicyclohexylurea in the course of the reaction.

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Mechanism

O
R

OH

R'NH2

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Cleaning Action of Soaps

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