ALDEHYDES AND

KETONES

THE CARBONYL GROUP

 Some naturally occurring aldehydes with strong odors
 Other odors that are far less pleasant can also becaused by aldehydes and ketones,-
for example, the pungent odor of formaldehyde or acetone, or the hangover caused by
acetaldehyde that results from drinking too many alcoholic beverages.

benzaldehyde
(almond flavor)
Why Study…
Aldehydes and Ketones?

 Much of organic chemistry is the chemistry of carbonyl compounds. Aldehydes and

ketones, in particular, are intermediates in the synthesis of many pharmaceutical
agents, in almost all biological pathways, and in numerous industrial processes, so an
understanding of their properties and reactions is essential.

(industrial solvent) (adhesive resins)

Introduction
 An aldehyde is often written as RCHO. Remember that the H atom is bonded to the
carbon atom, not the oxygen.
 a ketone is written as RCOR’ or, if both alkyl groups are the same, R2CO.

 The electronegative oxygen atom polarizes the carbonyl group,

making the carbonyl carbon electrophilic. As a result, aldehydes
and ketones react with nucleophiles.

 The relative reactivity of the carbonyl group is determined by the number of R groups
bonded to it.
Naming Aldehydes in the IUPAC System

 If the CHO is bonded to a chain of carbons, find the longest chain containing the
CHO group, and change the -e ending of the parent alkane to the suffix -al.
 If the CHO group is bonded to a ring, name the ring and add the suffix -carbaldehyde.
 Number the chain or ring to put the CHO group at C1, but omit this number from
the name. Apply all of the other usual rules of nomenclature.
Common (Trivial) Names for Aldehydes

 A common name for an aldehyde is formed by taking the common parent name and
adding the suffix -aldehyde.
 The carbon adjacent to the CHO is called the α carbon. The carbon bonded to the α
carbon is the β carbon, followed by the γ (gamma) carbon, the δ (delta) carbon, and so
forth down the chain. The last carbon in the chain is sometimes called the  (omega)
carbon.

CHO

Cl

-chlorocaproaldehyde
Naming Ketones in the IUPAC System

 Find the longest chain containing the carbonyl group, and change the -e ending of
the parent alkane to the suffix -one.
 Number the carbon chain to give the carbonyl carbon the lower number. Apply all
of the other usual rules of nomenclature.
 With cyclic ketones, numbering always begins at the carbonyl carbon, but the “1” is
usually omitted from the name. The ring is then numbered clockwise or
counterclockwise to give the first substituent the lower number.

Common Names for Ketones

 Most common names for ketones are formed by naming both alkyl groups on the
carbonyl carbon, arranging them alphabetically, and adding the word ketone.
 carbonyl group has a higher nomenclature priority than an alcohol or an amino group.
 If a compound has two functional groups, the one with the lower priority is indicated
by a prefix and the one with the higher priority by a suffix (unless one of the functional
groups is an alkene)
Problem 1
 Give the correct name for each compound.
Properties of Aldehydes and Ketones
Preparation of Aldehydes and Ketones
Preparation of Aldehydes and Ketones

Common Methods to Synthesize Aldehydes

Common Methods to Synthesize Ketones
 Aldehydes and ketones are also both obtained as products of the oxidative cleavage of alkenes

Problem 2
 What reagents are needed to convert each compound into butanal (CH3CH2CH2CHO)?

Problem 3
 What reagents are needed to convert each compound into acetophenone (C6H5COCH3)?
Problem 4
(a) Show how 2-butanone could be prepared by a procedure in which all of the carbons
originate in acetic acid (CH3CO2H).

(b) Two species of ants found near the Mediterranean use 2-methyl-4-heptanone as an
alarm pheromone. Suggest a synthesis of this compound from two 4-carbon
alcohols.
Reactions of Aldehydes and Ketones

 Reaction at the carbonyl carbon

 Reaction at the α carbon

The General Mechanism of Nucleophilic Addition

 Two general mechanisms are usually drawn for nucleophilic addition, depending on
the nucleophile (negatively charged versus neutral) and the presence or absence of an
acid catalyst.
 With negatively charged nucleophiles, nucleophilic addition follows the two-step
process—nucleophilic attack followed by protonation. This process occurs with
strong neutral or negatively charged nucleophiles.
 With some neutral nucleophiles, however, nucleophilic addition does not occur unless an acid
catalyst is added. The general mechanism for this reaction consists of three steps (not two), but
the same product results because H and Nu add across the carbonyl  bond.

 This protonated carbonyl group is much more electrophilic,

and much more susceptible to attack by a nucleophile.
 This step is unnecessary with strong nucleophiles like
hydride (H–). With weaker nucleophiles, however,
nucleophilic attack does not occur unless the carbonyl
group is first protonated.
Nucleophilic Addition of H–
 Treatment of an aldehyde or ketone with either NaBH4 or LiAlH4 followed by
protonation forms a 1° or 2° alcohol.
 NaBH4 and LiAlH4 serve as a source of hydride, H: – —the nucleophile—and the
reaction results in addition of the elements of H2 across the C–O π bond. Addition of
H2 reduces the carbonyl group to an alcohol

 Hydride reduction of aldehydes and ketones occurs via the two-step mechanism of
nucleophilic addition—that is, nucleophilic attack of H:– followed by protonation
Nucleophilic Addition of R– (RMgX or RLi)
 Treatment of an aldehyde or ketone with either an organolithium (R''Li) or Grignard
reagent (R''MgX) followed by water forms a 1°, 2°, or 3° alcohol containing a new C–C
bond.
 R"Li and R"MgX serve as a source of a carbanion (R'')–—the nucleophile—and the
reaction results in addition of the elements of R" and H across the C–O π bond

 Nucleophilic addition of the Grignard reagent to the carbonyl carbon forms an alkoxide
ion that is complexed with the magnesium ion.
 Addition of dilute acid breaks up the complex.
The Reactions of Aldehydes and Ketones with Grignard Reagents

 When a Grignard reagent reacts with formaldehyde, the product of the nucleophilic
addition reaction is a primary alcohol.

 When a Grignard reagent reacts with an aldehyde other than formaldehyde, the
product of the nucleophilic addition reaction is a secondary alcohol.
 When a Grignard reagent reacts with a ketone, the product of the nucleophilic addition
reaction is a tertiary alcohol.

 In the following reactions, the reagents above and below the reaction arrows are
numbered in order of use, indicating that the acid is not added until after the Grignard
reagent has reacted with the carbonyl compound.
Problem 5
 What products are formed when the following compounds react with CH3MgBr,
followed by the addition of dilute acid?

Problem 6
 3-methyl-3-hexanol can be synthesized from the reaction of 2-pentanone with
ethylmagnesium bromide. What other combinations of ketone and Grignard reagent
could be used to prepare the same tertiary alcohol?
Nucleophilic Addition of –CN

 Treatment of an aldehyde or ketone with

NaCN and a strong acid such as HCl adds the
elements of HCN across the carbon–oxygen π
bond, forming a cyanohydrin. This reaction
adds one carbon to the aldehyde or ketone,
forming a new C-C bond.
 Cyanohydrins can be reconverted to carbonyl compounds by treatment with base. This
process is just the reverse of the addition of HCN: deprotonation followed by
elimination of –CN.

 The addition of hydrogen cyanide to aldehydes and ketones is a synthetically useful

reaction because of the subsequent reactions that can be carried out on the
cyanohydrin.
 For example, the acid-catalyzed hydrolysis of a cyanohydrin forms an α-
hydroxycarboxylic acid
 The catalytic addition of two moles of Problem 7
hydrogen to the triple bond of a
 Draw the products of each reaction.
cyanohydrin produces a primary amine
with an OH group on the β-carbon.

Problem 8
 How can the following compounds be
prepared from a carbonyl compound that
has one less carbon than the desired
product?
The Wittig Reaction
 The Wittig reaction, named for German chemist Georg Wittig, who was awarded the
Nobel Prize in Chemistry in 1979 for its discovery.
 The Wittig reaction uses a carbon nucleophile, the Wittig reagent, to form alkenes.
When a carbonyl compound is treated with a Wittig reagent, the carbonyl oxygen atom
is replaced by the negatively charged alkyl group bonded to the phosphorus—that is,
the C=O is converted to a C=C.

 A Wittig reaction forms two new carbon–carbon bonds–one new σ bond and one new
π bond–as well as a phosphorus by-product, Ph3P=O (triphenylphosphine oxide)
The Wittig Reagent
 A Wittig reagent is an organophosphorus reagent. A Wittig reagent is an ylide.

 Wittig reagents are synthesized by a two-step procedure

 To synthesize the Wittig reagent, Ph3P=CH2, use these two steps:

Example
Answer
Mechanism of the Wittig Reaction

 Because the Wittig reaction forms two carbon–carbon bonds in a single reaction, it has
been used to synthesize many natural products, including β-carotene
Example How To Determine the Starting Materials for a Wittig Reaction Using Retrosynthetic Analysis

What starting materials are needed to synthesize alkene X by a Wittig reaction?

 Step [1] Cleave the carbon–carbon double bond into two components.

 Step [2] Compare the Wittig reagents. The preferred pathway uses a Wittig reagent derived from
an unhindered alkylhalide—CH3X or RCH2X
Comparing Methods of Alkene Synthesis
 For example, two methods can be used to convert cyclohexanone into alkene B
(methylenecyclohexane): a two-step method consisting of Grignard addition followed
by dehydration, or a one-step Wittig reaction
Problem 9
 What starting materials are needed to prepare each alkene by a Wittig reaction? When there are
two possible routes, indicate which route, if any, is preferred

Problem 10
 Show two methods to synthesize each alkene: a one-step method using a Wittig reagent,
and a two-step method that forms a carbon–carbon bond with an organometallic reagent
in one of the steps
Addition of 1° Amines
 Amines are classified as 1°, 2°, or 3° by the number of alkyl groups bonded to the
nitrogen atom.

 Both 1° and 2° amines react with aldehydes and ketones.

Formation of Imines
 Treatment of an aldehyde or ketone with a 1° amine affords an imine (also called a
Schiff base). The overall reaction results in replacement of C=O by C=NR
Mechanism Imine Formation from an Aldehyde or Ketone
 Example: Problem 11
 Draw the product formed when
CH3CH2CH2CH2NH2 reacts with each
carbonyl compound in the
presence of mild acid.

Problem 12
 What 1° amine and carbonyl compound
are needed to prepare each imine?
Example:
Addition of 2° Amines
Formation of Enamines
 2° amine reacts with an aldehyde or ketone to form carbinolamines. Carbinolamine
intermediates can dehydrate to a carbon–carbon double bond. The product of this
dehydration is an alkenyl-substituted amine (alkene + amine = enamine).

Example:
Mechanism Enamine Formation from an Aldehyde or Ketone
The formation of imines and enamines compared
Imine and Enamine Hydrolysis
 Hydrolysis of imines and enamines forms aldehydes and ketones.

Example:
 What carbonyl compound and amine are formed by the hydrolysis of each compound?
Answer
Reductive Amination
Addition of H2O—Hydration

 Treatment of a carbonyl compound with H2O in the presence of an acid or base

catalyst adds the elements of H and OH across the carbon–oxygen  bond, forming a
gem-diol or hydrate

 Hydration of a carbonyl group gives a good yield of gem-diol only with an unhindered
aldehyde like formaldehyde, and with aldehydes containing nearby electron-
withdrawing groups.
 Increasing the number of alkyl groups on the carbonyl carbon decreases the amount of
hydrate at equilibrium.
Mechanism Hydrate Formation

 Acid-Catalyzed Addition of H2O to a Carbonyl Group

 Base-Catalyzed Addition of H2O to a Carbonyl Group

Addition of Alcohols—Acetal Formation

 The product formed when one equivalent of an alcohol adds to

an aldehyde or a ketone is called a hemiacetal. The product
formed when a second equivalent of alcohol is added is called
an acetal

 Acetals are not ethers, even though both functional groups

contain a C–O σ bond. Having two C–O σ bonds on the same
carbon atom makes an acetal very different from an ether.
Exercise

 Label each compound as an acetal, a hemiacetal, or an ether.

 Label each compound as an acetal, a hemiacetal, or a hydrate

 Acetal formation is catalyzed by acids, commonly p-toluenesulfonic acid (TsOH).

 When a diol such as ethylene glycol is used in place of two equivalents of ROH, a
cyclic acetal is formed. Both oxygen atoms in the cyclic acetal come from the diol.
Mechanism Acetal Formation
 The synthesis of acetals is reversible,
and often the equilibrium favors
reactants, not products. In acetal
synthesis, however, water is formed as
a by-product, so the equilibrium can be
driven to the right by removing the
water as it is formed (Le Châtelier’s
principle)
.
 A drying agent can be added that
reacts with the water, or more
commonly, the water can be distilled
from the reaction mixture as it is
formed by using a Dean–Stark trap
Hydrolysis of Acetals

 Conversion of an aldehyde or ketone to an acetal is a reversible reaction, so an acetal

can be hydrolyzed to an aldehyde or ketone by treatment with aqueous acid.
 Although acetals are hydrolyzed to Problem 14
aldehydes and ketones in aqueous acid,  Identify the acetal in oleandrin, and draw
acetals are stable in basic solutions: the products formed by acid catalyzed
hydrolysis of the acetal.

Problem 13
 Identify the acetal carbons in A, and draw
the products formed by hydrolysis of A
with aqueous acid
Acetals as Protecting Groups
 If a compound has two functional groups that will react with a given reagent, but you
want only one of them to react, then you must protect the other functional group from
the reagent.
 A group that protects a functional group from a synthetic operation that the functional
group would not otherwise survive is called a protecting group.
 Acetals are used to protect aldehydes and ketones from undesired reactions

 For example, suppose you want to convert the keto ester shown next into a
hydroxyketone. Both functional groups of the keto ester will be reduced by LiAlH4, and the
one that you don’t want to react—the keto group—is the more reactive of the two groups.
 To solve this problem we can use a protecting group to block the more reactive ketone
carbonyl group. The overall process requires three steps.
[1] Protect the interfering functional group—the ketone carbonyl.
[2] Carry out the desired reaction—reduction.
[3] Remove the protecting group (“deprotection”)

 Example:
Cyclic Hemiacetals (Lactols)
 Although acyclic hemiacetals are  cyclic hemiacetals are formed by
generally unstable and therefore not intramolecular cyclization of hydroxyl
present in appreciable amounts at aldehydes/ketones.
equilibrium, cyclic hemiacetals containing
five- and six-membered rings are stable
compounds that are readily isolated.
The Conversion of Cyclic Hemiacetals to Acetals
 Cyclic hemiacetals can be converted to  The overall result of this reaction is the
acetals by treatment with an alcohol and replacement of the hemiacetal OH group
acid. by an OCH3 group.

Mechanism:
Problem 15
 What lactol (cyclic hemiacetal) is formed from intramolecular cyclization of each
hydroxy aldehyde?

Problem 16
 Draw the products of each reaction.
A Preview of Oxidation and Reduction
Reductions of Ketones and Aldehydes
Hydride Reductions
 NaBH4 reduces ketones to secondary  NaBH4 selectively reduces aldehydes and
alcohols and aldehydes to primary ketones in the presence of most other
alcohols. LiAIH4 also accomplishes these functional groups. LiAlH4 reduces
reductions, but it is a more powerful aldehydes and ketones and many other
reducing agent, and it is much more functional groups as well
difficult to work with. Sodium borohydride
is preferred for simple reductions of
ketones and aldehydes.
Reductions of Ketones and Aldehydes
Catalytic Hydrogenation
 Catalytic hydrogenation also reduces aldehydes and ketones to 1° and 2° alcohols,
respectively, using H2 and Pd-C (or another metal catalyst). The metal catalyst (Pd-C)
provides a surface that binds the carbonyl starting material and H2, and two H atoms
are sequentially transferred with cleavage of the π bond.

 The most common catalyst for catalytic hydrogenation of ketones and aldehydes is
Raney nickel.
 When a compound contains both a carbonyl group and a carbon–carbon double bond,
selective reduction of one functional group can be achieved by proper choice of
reagent.

 Thus, cyclohex-2-enone, a compound that contains both a carbon–carbon double

bond and a carbonyl group, can be reduced to three different compounds—an allylic
alcohol, a carbonyl compound, or an alcohol—depending on the reagent.
Reductions of Ketones and Aldehydes
Deoxygenation of Ketones and Aldehydes
 A deoxygenation replaces the carbonyl oxygen atom of a ketone or aldehyde with two
hydrogen atoms, reducing the carbonyl group past the alcohol stage all the way to a
methylene group.

 The following equation compares deoxygenation with the common hydride reductions
that give alcohols.
 Clemmensen Reduction

 Wolff-Kishner Reduction
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. Because ketones
have no H on the carbonyl carbon, they do not undergo
this oxidation reaction.
Oxidative Chemical Tests for Aldehydes
Tollens’ Test (Silver mirror Test)
 Mixing aqueous silver nitrate with aqueous ammonia produces a
solution known as Tollens’ reagent. The reagent contains the
diaminosilver(I) ion, Ag(NH3)2+. Although this ion is a very weak
oxidizing agent, it oxidizes aldehydes to carboxylate anions.
 Simple hydrocarbons, ethers, ketones and even alcohols do not
react with the Tollens reagent
Fehling’s and Benedict’s Test
 Fehling's solution and Benedict's solution are variants of essentially
the same thing. Both contain complexed copper(II) ions in an alkaline
solution.
 Fehling's solution contains copper(II) ions complexed with tartrate ions
in sodium hydroxide solution. Benedict's solution contains copper(II)
ions complexed with citrate ions in sodium carbonate solution.
 the precipitation of red copper(I) oxide indicates the presence of an
aldehyde function.
The Baeyer-Villiger Oxidation
 When treated with a peroxy acid, ketones can be converted into esters via the
insertion of an oxygen atom.

 This reaction, discovered by Adolf von Baeyer and Victor Villiger in 1899, is called the
Baeyer–Villiger oxidation
 Mechanism:
 When an unsymmetrical ketone is treated with a peroxy acid, formation of the ester is
regioselective; for example:

 In this case, the oxygen atom is inserted on the left side of the carbonyl group, rather
than the right side. This occurs because the isopropyl group migrates more rapidly than
the methyl group during the rearrangement step of the mechanism.
 Studies of the migration tendencies of different groups have established the following
order:
Problem 17
 Give the products of the following reactions
The Acidity of an α-Hydrogen
 The α-hydrogens of carbonyl compounds are acidic.

 The carbonyl group is strongly electron withdrawing, and when a carbonyl compound
loses an a proton, the anion that is produced, called an enolate, is stabilized by
delocalization.
 If the α-carbon is between two carbonyl groups, the acidity of its α-hydrogen is even
greater

 The acidity of α-hydrogens bonded to carbons flanked by two carbonyl groups

increases because the electrons left behind when the proton is removed can be
delocalized onto either of two oxygens
Keto–Enol Tautomers
 A ketone exists in equilibrium with its  The enol tautomer is greater for a β-
enol tautomer. Keto–enol tautomers differ diketone because the enol tautomer is
in the location of a double bond and a stabilized both by intramolecular hydrogen
hydrogen bonding and by conjugation of the C=C
with the second carbonyl group

 For most ketones, the enol tautomer is

much less stable than the keto tautomer.
 Keto–enol interconversion (also called tautomerization) can be catalyzed by either a
base or an acid
Halogenation at the α-Carbon

Acid-Catalyzed Halogenation Base-Promoted Halogenation

 When halogen is added to a acid solution  When excess halogen is added to a basic
of an aldehyde or a ketone, the halogen solution of an aldehyde or a ketone, the
replaces one of the α-hydrogens. halogen replaces all of the α-hydrogens.
The Haloform Reaction
 Unlike its acid-catalyzed counterpart, halogenation in base cannot normally be limited
to monohalogenation. Methyl ketones, for example, undergo a novel polyhalogenation
and cleavage on treatment with a halogen in aqueous base.

 This is called the haloform reaction because the trihalomethane (haloform) produced is
chloroform, bromoform, or iodoform, depending, of course, on the halogen used.
 The haloform reaction is synthetically useful as a means of converting methyl ketones
to carboxylic acids..
 When iodine is the halogen component,  Mechanism:
the bright yellow solid iodoform (CHI3)
results.
 This version is the basis of the iodoform
classification test for methyl ketones and
methyl secondary alcohols (which are
oxidized to methyl ketones first under the
reaction conditions)
Alkylation at the α-Carbon
 Treatment of an aldehyde or ketone with base
and an alkyl halide (RX) results in alkylation—
the substitution of R for H on the α-carbon
atom. Alkylation forms a new carbon–carbon
bond on the α-carbon.
 Direct alkylation is carried out by a two-step
process:

Lithium diisopropylamide
(LDA), strong base
Alkylation of Unsymmetrical Ketones
 With an unsymmetrical ketone, two possible enolates can be formed.

 The kinetic enolate is favored by: a strong nonnucleophilic base (LDA); polar aprotic
solvent; low temperature (-78oC).
 The thermodynamic enolate is favored by: a strong base (NaOEt, KOC(CH3)3); room
temperature.
Problem 18
 Convert each compound to its enol or keto
tautomer.