Adama Science and Technology University
School of Applied Natural Science
Department of Applied Chemistry
Organic Chemistry II(chem 2232)
Chapter 3
Reactions of Carbonyl Compounds
Course Instructor: Yilkal Matebie([Link])
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Structure of carbonyl compounds
X = H then aldehyde
X= R then ketone
O X = OH then carboxylic acid
X = Cl then acid chloride
C X = OR then ester (cyclic esters = lactones)
R X X = OCOR then acid anhydride
X = N then amide (cyclic amides = lactams)
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Introduction
Many compounds found in nature have aldehyde or ketone
functional groups.
Aldehydes have pungent odors, whereas ketones tend to
smell sweet.
Vanillin and cinnamaldehyde are examples of naturally
occurring aldehydes.
Ketones, carvone and camphor are responsible for the
characteristic sweet odors of spearmint leaves, caraway
seeds, and the camphor tree.
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Two ketones that are of biological importance illustrate
how a small difference in structure can be responsible
for a large difference in biological activity:
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How Aldehydes and Ketones React
Aldehydes and ketones undergoes
Nucleophilic Addition Reaction
Addition-Elimination Reactions
Enolization-Ketonization Reaction
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1. Nucleophilic Addition Reactions
A. Addition of Water
Aldehydes and ketones undergo a nucleophilic addition
reaction with water to yield geminal diols.
Water adds to an aldehyde or a ketone to form a hydrate.
A hydrate is a molecule with two OH groups on the same
carbon.
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Mechanism for acid-catalyzed hydrate formation
Hydration of an aldehyde or ketone can also be catalyzed by
hydroxide ion.
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B. Addition of Alcohol
when one equivalent of an alcohol adds to an aldehyde
or ketone the product is hemiacetal and hemiketal
respectively.
when a second equivalent of alcohol is added to an
aldehyde and ketone the product is acetal and ketal
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respectively.
Mechanism for acid-catalyzed acetal or ketal formation
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Ketones (or aldehydes) react with 1,2-diols to form five-
membered ring ketals (or acetals) and with 1,3-diols to
form six-membered ring ketals (or acetals)
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Problem 1:
Write the structures of the cyclic acetals derived
from each of the following.
A. Cyclohexanone and ethylene glycol
B. Benzaldehyde and 1,3-propanediol
C. Isobutyl methyl ketone and ethylene glycol
D. Isobutyl methyl ketone and 2,2-dimethyl-
1,3- propanediol
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C. Reaction with Hydrogen Cyanide
Hydrogen cyanide adds to aldehydes and ketones to
form cyanohydrins.
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Converting aldehydes and ketones to
cyanohydrins is of synthetic value for two reasons:
1. New carbon–carbon bond is formed, and
2. cyano group in the product can be converted
to a carboxylic acid function (CO2H) by
hydrolysis
3. To an amine of the type CH2NH2 by reduction
The acid-catalyzed hydrolysis of a cyanohydrin
forms an α– hydroxy carboxylic acid.
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The catalytic addition of hydrogen to a cyanohydrin
produces a primary amine with an OH group on the β-
carbon.
PROBLEM: How can the following compounds be
prepared, starting with a carbonyl compound with
one fewer carbon atoms than the desired product?
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D. Addition of Grignard Reagents
Grignard reagent (R-MgX) add to aldehydes and ketones,
yielding alcohols in which new C-C bond formed
Grignard reagent reacts with formaldehyde, the
product is a primary alcohol.
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Grignard reagent reacts with an aldehyde the product is a
secondary alcohol.
Grignard reagent reacts with a ketone the product is a
tertiary alcohol.
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Example
A Grignard reagent can also react with carbon dioxide.
The product of the reaction is a carboxylic acid.
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Esters also react with Grignard reagents to form tertiary
alcohols
Problem: Which of the following tertiary alcohols cannot be prepared from the
reaction of an ester with excess Grignard reagent?
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E. Reaction with Acetylide Ions
Terminal alkyne can be converted into an acetylide
ion by a strong base.
Problem: Show how the following compounds could be
prepared, using ethyne as one of the starting materials.
A. 1-pentyn-3-ol
B. 2-methyl-3-hexyn-2-ol
C. 1-phenyl-2-butyn-1-ol
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F. Hydride Additions
Addition of hydride ion to an aldehyde or ketone forms
an alkoxide ion then protonation by an acid produces an
alcohol.
Aldehydes are reduced to primary alcohols and
ketones are reduced to secondary alcohols.
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Problem: What alcohols are obtained from the reduction
of the following compounds with sodium borohydride?
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2. Addition-Elimination Reactions
Aldehydes and ketones react with a primary amine
to form an imine.
An imine is a compound with a carbon–nitrogen
double bond.
The imine obtained from the reaction of a carbonyl
compound and a primary amine is often called a
Schiff base.
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Aldehydes and ketones react with a secondary amine
to form an enamine.
An enamine is an α,β-unsaturated tertiary amine.
Double bond at α,β-position relative to the nitrogen
atom.
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A. Addition of Primary Amines
Aldehydes and ketones react with primary amines to
form imines.
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Mechanism for imine formation
Overall reaction is a •HB+ represents any species in the
nucleophilic addition– solution that is capable of
elimination reaction. donating a proton .
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B. Addition of Secondary Amine
Aldehydes and ketones react with secondary amines
to form enamines.
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Mechanism for Enamine Formation
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Imine Derivatives
Hydroxylamine(NH2OH), hydrazine(NH2NH2) and
semicarbazide (NH2NHCONH2) react with aldehydes and
ketones to form imine derivatives.
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Phenyl-substituted hydrazines react with aldehydes
and ketones to form phenylhydrazones.
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C. Wolff–Kishner Reduction
Ketone or an aldehyde is heated in a basic solution of
hydrazine, the carbonyl group is converted into a
methylene group.
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D. Wittig Reaction
An aldehyde or a ketone reacts with a phosphonium
ylide to form an alkene.
An ylide is a compound that has opposite charges on
adjacent covalently bonded atoms.
Wittig reaction is the reaction of an aldehyde or a
ketone with a phosphonium ylide to form an alkene.
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Example
Mechanism
Preparation phosphonium ylide
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Problem
1. What carbonyl compound and what phosphonium ylide
are required for the synthesis of the following alkenes?
2. Identify the alkene product in each of the following
Wittig reactions:
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Reactivity's of Carboxylic Acids
and Carboxylic Acid Derivatives
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3. Enolization-Ketonization reactions
A ketone exists in equilibrium with its enol tautomer.
Keto–enol tautomers differ in the location of a double
bond and a hydrogen.
base-catalyzed keto–enol interconversion
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Acid-catalyzed keto–enol interconversion
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A. α-Halogenation Aldehydes and Ketones
Aldehydes and ketones react with halogens(Br2, Cl2 or I2)
by substitution of one of the α -hydrogens:
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Alkylations at the α-Carbon
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Two different products can be formed when the
ketone is not symmetrical.
Kinetic product obtained
Thermodynamic product,
from kinetic enolate
obtained from thermodynamic
enolate
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SYNTHESIS OF ASPIRIN
Kolbe–Schmitt carboxylation reaction
Exercise :How could you prepare 4-methyl-3-hexanone from a
ketone containing no more than six carbon atoms?
How could each of the following compounds be prepared from a ketone and an alkyl
halide?
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Michael Reaction
Alkylation at β -Carbon
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Aldol Addition
An aldol addition is a reaction between two molecules of
an aldehyde or two molecules of a ketone.
When the reactant is an aldehyde, the addition product
is a β-hydroxyaldehyde.
When the reactant is a ketone, the addition product is a
β-hydroxy ketone .
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Problem
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Dehydration of Aldol Addition Products:
Aldol addition product is dehydrated, the overall reaction is
called an aldol condensation.
A condensation reaction is a reaction that combines two
molecules while removing a small molecule (usually water
or an alcohol
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Mixed Aldol Addition
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Problem
Give the products obtained from mixed aldol additions of the following compounds:
Describe how the following compounds could be prepared using
an aldol addition in the first step of the synthesis:
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Claisen Condensation
Two molecules of an ester undergo a condensation reaction, the
reaction is called a Claisen condensation to form β-keto ester.
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Dickman condensation
Intramolecular Claisen Condensations
1,6-diester undergo an intramolecular Claisen condensation to forming
a five-membered ring β-keto-ester .
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A six-membered ring β-keto ester is formed from a
Dieckmann condensation of a 1,7-diester.
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