Lecture Notes in Chem.
2232
(Organic Chemistry II )
Dr. Joel R. Salazar
Chapter 4
Aldehydes and Ketones .
Nucleophilic Addition to
the Carbonyl Group
IUPAC Names for Ketones
Replace -e with -one. Indicate the position
of the carbonyl with a number.
Number the chain so that carbonyl carbon
has the lowest number.
For cyclic ketones the carbonyl carbon is
assigned the number 1.
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Examples
O O
CH3 C CH CH3
CH3
3-methyl-2-butanone Br
3-bromocyclohexanone
O
CH3 C CH CH2OH
CH3
4-hydroxy-3-methyl-2-butanone
=>
Naming Aldehydes
IUPAC: Replace -e with -al.
The aldehyde carbon is number 1.
If -CHO is attached to a ring, use the suffix
-carbaldehyde.
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Examples
CH3 O
CH3 CH2 CH CH2 C H
3-methylpentanal
CHO
2-cyclopentenecarbaldehyde
=>
Name as Substituent
On a molecule with a higher priority
functional group, C=O is oxo- and -CHO is
formyl.
Aldehyde priority is higher than ketone.
COOH
O CH3 O
CH3 C CH CH2 C H
CHO
3-methyl-4-oxopentanal 3-formylbenzoic acid
=>
Common Names for Ketones
Named as alkyl attachments to -C=O.
Use Greek letters instead of numbers.
O O
CH3 C CH CH3 CH3CH C CH CH3
CH3 Br CH3
methyl isopropyl ketone a-bromoethyl isopropyl ketone
=>
Historical Common Names
O O
C
CH3 C CH3 CH3
acetone
O
C
acetophenone
benzophenone
=>
Aldehyde Common Names
Use the common name of the acid.
Drop -ic acid and add -aldehyde.
◼ 1 C: formic acid, formaldehyde
◼ 2 C’s: acetic acid, acetaldehyde
◼ 3 C’s: propionic acid, propionaldehyde
◼ 4 C’s: butyric acid, butyraldehyde.
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Boiling Points
More polar, so higher boiling point than
comparable alkane or ether.
Cannot H-bond to each other, so lower
boiling point than comparable alcohol.
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Solubility
Good solvent for alcohols.
Lone pair of electrons on oxygen of carbonyl
can accept a hydrogen bond from O-H or
N-H.
Acetone and acetaldehyde are miscible in
water.
=>
Synthesis of Aldehydes
◼ Aldehydes by Oxidation of 1o Alcohols
Primary alcohols are oxidized to aldehydes by PCC
◼ Aldehydes by Reduction of Acyl Chlorides, Esters and Nitriles
Reduction of carboxylic acid to aldehyde is impossible to stop at
the aldehyde stage
◼ Aldehydes are much more easily reduced than carboxylic acids
Reduction to an aldehyde can be accomplished by
using a more reactive carboxylic acid derivatives
such as an acyl chloride, ester or nitrile and a less
reactive hydride source
◼ The use of a sterically hindered and therefore less reactive
aluminum hydride reagent is important
Acid chlorides react with lithium tri-tert-
butoxyaluminum hydride at low temperature to give
aldehydes
Hydride is transferred to the carbonyl carbon
◼ As the carbonyl re-forms, the chloride (which is a good leaving
group) leaves
Reduction of an ester to an aldehyde can be
accomplished at low temperature using DIBAL-H
◼ As the carbonyl re-forms, an alkoxide leaving group departs
Synthesis of Ketones
◼ Ketones from Alkenes, Arenes, and 2o Alcohols
Ketones can be made from alkenes by ozonolysis
Aromatic ketones can be made by Friedel-Crafts
Acylation
Ketones can be made from 2o alcohols by oxidation
◼ Ketones from Alkynes
Markovnikov hydration of an alkyne initially yields a
vinyl alcohol (enol) which then rearranges rapidly to a
ketone (keto)
The rearrangement is called a keto-enol tautomerization
◼ This rearrangement is an equilibrium which usually favors the
keto form
Terminal alkynes yield ketones because of the
Markovnikov regioselectivity of the hydration
◼ Ethyne yields acetaldehyde
◼ Internal alkynes give mixtures of ketones unless they are
symmetrical
◼ Ketones from Lithium Dialkylcuprates
An acyl chloride can be coupled with a dialkylcuprate
to yield a ketone (a variation of the Corey-Posner,
Whitesides-House reaction)
◼ Ketones from Nitriles
Organolithium and Grignard reagents add to nitriles to
form ketones
◼ Addition does not occur twice because two negative charges
on the nitrogen would result
Solved Problem
Synthesize 5-nonanone using 1-butanol as your only
starting material
◼ Solved Problem : Synthesize 5-nonanone using 1-
butanol as your only starting material
◼ Relative Reactivity: Aldehydes versus Ketones
Aldehydes are generally more reactive than ketones
◼ The tetrahedral carbon resulting from addition to an
aldehyde is less sterically hindered than the tetrahedral
carbon resulting from addition to a ketone
◼ Aldehyde carbonyl groups are more electron deficient
because they have only one electron-donating group attached
to the carbonyl carbon
The Addition of Alcohols: Hemiacetals and
Acetals
◼ Hemiacetals
An aldehyde or ketone dissolved in an alcohol will
form an equilibrium mixture containing the
corresponding hemiacetal
◼ A hemiacetal has a hydroxyl and alkoxyl group on the same
carbon
◼ Acylic hemiacetals are generally not stable,
however, cyclic five- and six-membered ring
hemiacetals are more stable
Hemiacetal formation is catalyzed by either acid or
base
Dissolving aldehydes (or ketones) in water causes
formation of an equilibrium between the carbonyl
compound and its hydrate
◼ The hydrate is also called a gem-diol (gem i.e. geminal,
indicates the presence of two identical substituents on the
same carbon)
◼ The equilibrum favors a ketone over its hydrate because the
tetrahedral ketone hydrate is sterically crowded
◼ Acetals
An aldehyde (or ketone) in the presence of excess
alcohol and an acid catalyst will form an acetal
◼ Formation of the acetal proceeds via the corresponding
hemiacetal
◼ An acetal has two alkoxyl groups bonded to the same carbon
Acetal formation from ketones and simple alcohols is less
favorable than formation from aldehydes
Acetals are stable when isolated and purified
Acetal formation is reversible
◼ An excess of water in the presence of an acid catalyst will
hydrolyze an acetal to the corresponding aldehyde (or
ketone)
Cyclic Acetals
◼ Such cyclic acetals are often used as protecting groups for
aldehydes and ketones
◼ Formation of cyclic 5- and 6- membered ring acetals from
ketones is, however, favorable
◼ These protecting groups can be removed using dilute
aqueous acid
◼ Acetals as Protecting Groups
Acetal protecting groups are stable to most reagents
except aqueous acid
Example: An ester can be reduced in the presence of a
ketone protected as an acetal
◼ Thioacetals
Thioacetals can be formed by reaction of an aldehyde
or ketone with a thiol
◼ This sequence provides a way to remove an aldehyde or
ketone carbonyl oxygen
Thioacetals can be converted to CH2 groups by hydrogenation using
a catalyst such as Raney nickel
The Addition of Primary and Secondary
Amines
Aldehydes and ketones react with primary amines
(and ammonia) to yield imines
◼ They react with secondary amines to yield enamines
◼ Imines
These reactions occur fastest at pH 4-5
◼ Mild acid facilitates departure of the hydroxyl group from
the aminoalcohol intermediate without also protonating the
nitrogen of the amine starting compound
Imine Derivatives
Addition of amines with an atom containing a lone pair of
electrons on the adjacent atom occurs very readily, giving
useful, stable imines
For example, hydroxylamine forms oximes and 2,4-
dinitrophenylhydrazine readily forms 2,4-
dinitrophenylhydrazones
◼ These are usually solids and help in characterizing liquid
ketones or aldehydes by melting points
Nucleophilic Addition of Hydrazine: The
Wolff–Kishner Reaction
Treatment of an aldehyde or ketone with hydrazine, H2NNH2 and
KOH converts the compound to an alkane
Originally carried out at high temperatures but with dimethyl
sulfoxide as solvent takes place near room temperature
◼ Enamines
Secondary amines cannot form a neutral imine by
loss of a second proton on nitrogen
◼ An enamine is formed instead
The Addition of Hydrogen Cyanide
Aldehydes and ketone react with HCN to form a
cyanohydrin
◼ A catalytic amount of cyanide helps to speed the reaction
The cyano group can be hydrolyzed or reduced
◼ Hydrolysis of a cyanohydrin produces an a-
hydroxycarboxylic acid
◼ Reduction of a cyanohydrin produces aminoalcohol
The Addition of Ylides: The Wittig Reaction
Aldehydes and ketones react with phosphorous ylides
to produce alkenes
◼ An ylide is a neutral molecule with adjacent positive and
negative charges
Reaction of triphenylphosphine with a primary or
secondary alkyl halide produces a phosphonium salt
◼ The phosphonium salt is deprotonated by a strong base to
form the ylide
Addition of the ylide to the carbonyl leads to formation of a
four-membered ring oxaphosphetane
◼ The oxaphophetane rearranges to the alkene and triphenylphosphine
oxide
◼ The driving force for the last reaction is formation of the very strong
phosphorus-oxygen double bond in triphenylphosphine oxide
The overall result of a Wittig reaction is formation of
a C=C bond from a C=O bond
Solved Problem:
Make 2-Methyl-1-phenylpropene by a Wittig
reaction
Solved Problem: Make 2-Methyl-1-phenylprop-1-ene
by a Wittig reaction
Solved Problem: Make 2-Methyl-1-phenylprop-1-ene
by a Wittig reaction
The Horner-Wadsworth-Emmons reaction employs a
phosphonate ester and generally leads to formation of
an (E)-alkene
The Cannizzaro Reaction: Biological
Reductions
The adduct of an aldehyde and OH- can transfer
hydride ion to another aldehyde C=O resulting in a
simultaneous oxidation and reduction
(disproportionation)
The Addition of Organometallic Reagents:
The Reformatsky Reaction
The Reformatsky reaction involves addition of an
organozinc reagent to an aldehyde or ketone
◼ The organozinc reagent is made from an a-bromo ester;
the reaction gives a b-hydroxy ester
◼ The b-hydroxyester is easily dehydrated to an
a,b-unsaturated ester
Oxidation of Aldehydes and Ketones
Aldehydes are generally much more easily oxidized
than ketones
◼ The Baeyer-Villiger Oxidation of Aldehydes and
Ketones
The Baeyer-Villeger reaction results in insertion of an
oxygen atom adjacent to a ketone or aldehyde
carbonyl
◼ Oxidation of a ketone yields an ester
◼ A peroxyacid such as m-chloroperbenzoic
(MCPBA) acid is used
The migratory aptitude of a group attached to a
carbonyl is H > phenyl > 3o alkyl > 2o alkyl >
1o alkyl > methyl
Chemical Analysis of Aldehydes and Ketones
◼ Tollens’ Test (Silver Mirror Test)
Aldehydes and ketones can be distinguished from
each other on the basis of the Tollens test
◼ The presence of an aldehyde results in formation of a silver
mirror (by oxidation of the aldehyde and reduction of the
silver cation)
◼ a-Hydroxyketones also give a positive Tollens’ test
The Addition of Sulfur Ylides to
Aldehydes and Ketones
Sulfur ylides react as nucleophiles at the carbonyl
carbon of aldehydes and ketones to produce epoxide