Download Aldehydes and Ketones

ALDEHYDE
& KETONES
ROHAZITA BAHARI
COURSE OUTCOMES
INVOLVED
CO #3: Ability to DEMONSTRATE the
reactions involving alcohol, ether, aldehyde,
ketone, carboxylic acid and aromatic
compounds
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OUTLINES
 Naming of Aldehyde and Ketones
 Relative Reactivity of Carbonyl Group
 Oxidation Reaction of Aldehydes and Ketones
 Nucleophilc Addition Reaction
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ALDEHYDES AND KETONES
 Aldehydes (RCHO) and ketones (R2CO) are characterized by the the carbonyl
functional group (C=O)
 The compounds occur widely in nature as intermediates in metabolism and
biosynthesis
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NAMING ALDEHYDES :
Aldehydes are named by replacing the terminal -e of the
corresponding alkane name with –al
The parent chain must contain the CHO group
• The CHO carbon is numbered as C1
Ethanal
acetaldehyde
Propanal
Propionaldehyde
2-Ethyl-4-methylpentanal
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N A M I N G A L D E H Y D E S A N D K E TO N E S
(Common)
Methanal
(IUPAC)
(Common)
Propanone (IUPAC)
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NAMING ALDEHYDES
If the CHO group is attached to a ring, use the suffix
carbaldehyde.
Cyclohexanecarbaldehyde
2-Naphthalenecarbaldehyde
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NAMING ALDEHYDES:
 Common Names end in aldehyde
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NAMING KETONES
Replace the terminal -e of the alkane name with –one
Parent chain is the longest one that contains the ketone grp
• Numbering begins at the end nearer the carbonyl carbon
3-Hexanone
(New: Hexan-3-one)
4-Hexen-2-one
2,4-Hexanedione
(New: Hex-4-en-2-one) (New: Hexane-2,4-dione)
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KETONES WITH COMMON
NAMES
 IUPAC retains well-used but unsystematic names for a few ketones
Acetone
Acetophenone
Benzophenone
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K E TO N E S A N D A L D E H Y D E S A S
SUBSTITUENTS
The R–C=O as a substituent is an acyl group, used
with the suffix -yl from the root of the carboxylic acid
 The prefix oxo- is used if other functional groups are present
and the doubly bonded oxygen is labeled as a substituent on a
parent chain
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PHYSICAL PROPERTIES
Have higher boiling points than hydrocarbon because
they are more polar and the forces between molecules are
stronger
More soluble than hydrocarbons but less soluble than
alcohols in water
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RELATIVE RECTIVITY
OF THE CARBONYL
GROUP
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THE RELATIVE
REACTIVITIES OF
CARBONYL GROUP
 The partial positive charge on the carbonyl carbon causes that carbon to
be attacked by nucleophiles:
 An aldehyde has a greater partial positive charge on its carbonyl carbon than does
a ketone:
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ALDEHYDES ARE MORE
REACTIVE THAN KETONES
 Steric factors contribute to the reactivity of an aldehyde.
• The carbonyl carbon of an aldehyde is more accessible to
the nucleophile because the hydrogen attached to the carbonyl
carbon of an aldehyde is smaller than the second alkyl group
to carbonyl carbon of a ketone.
• Ketones have greater steric crowding in their transition
states, so they have less stable transition states.
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ALKYL GROUP STABILIZED THE
R E AC TA NT
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The reactivity of carbonyl compounds is also
related to the basicity of Y–: (lone pair of an atom)
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 Carbonyl compound other than
aldehyde and ketone have a lone
pair (Y-)on an atom which
attached to carbonyl compound
group that can be shared by
resonance e- donation. This makes
the carbonyl carbon less electron
deficient and less reactive.
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HOW ALDEHYDES
AND KETONES REACT
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OXIDATION OF ALDEHYDES &
KETONES
 CrO3 in aqueous acid oxidizes aldehydes to carboxylic acids
(acidic conditions)
 Tollens’ reagent Silver oxide, Ag2O, in aqueous ammonia
oxidizes aldehydes (basic conditions)
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HYDRATION OF
ALDEHYDES
Aldehyde oxidations occur through 1,1-diols (“hydrates”)
Reversible addition of water to the carbonyl group
Aldehyde hydrate is oxidized to a carboxylic acid by usual
reagents for alcohols
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KETONES OXIDIZE WITH
DIFFICULTY
Undergo slow cleavage with hot, alkaline KMnO4
C–C bond next to C=O is broken to give carboxylic acids
Reaction is practical for cleaving symmetrical ketones
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REACTIONS OF ALDEHYDES
AND KETONES
 Aldehydes and ketones undergo a variety of reactions that lead to
many different product. The most common reactions are
NUCLEOPHILIC ADDITION REACTIONS.
 The main reactions of the carbonyl group are nucleophilic
addition to the carbon-oxygen double bond.
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NUCLEOPHILIC
ADDITION REACTION
 When a nucleophile attacks an aldehyde or ketone carbon, there is no
leaving group. The incoming nucleophile simply “pushes” the electrons in the
pi bond up to the oxygen. (eg: )
 Alternatively, if start with the minor resonance contributor: attack by a
nucleophile on a carbocation. (eg: )
 After the carbonyl is attacked by the nucleophile, the negatively charged
oxygen has the capacity to act as a nucleophile. However, most commonly the
oxygen acts instead as a base, abstrating a proton from a nearby acid group in
the solvent or enzyme active side. (eg)
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NUCLEOPHILES
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RELATIVE REACTIVITY OF
ALDEHYDES AND KETONES
 Aldehyde are usually more reactive toward nucleophilic substitutions than
ketones because of both steric and electronic effects. In aldehydes, the relatively
small hydrogen atom is attached to one side of the carbonyl group. While a larger
R group is affixed to the other side.
 In ketones, however, R group are attached to both sides of the carbonyl
group. Thus, steric hindrance is less in aldehydes than in ketones.
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 Electronically, aldehydes have only one R group to supply electrons towards
the partially positive carbonyl carbon, while ketones have two electronsupplying group attached to the carbonyl carbon. The greater amount of
electrons being supplied to the carbonyl carbon, the less partial positive charge
on this atom and the weaker it will become as a nucleus.
 Due to differences in electronegativities, the carbonyl group is polarized.
The carbon atom has a partial positive charge, and the oxygen atom has a
partially negative charge.
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R E L AT I V E R E A C T I V I T Y O F
A L D E H Y D E S A N D K E TO N E S
 Aldehydes are generally more reactive than ketones in
nucleophilic addition reactions
• Aldehyde C=O is more polarized than ketone C=O
• Ketone has more electron donation alkyl groups, stabilizing the
C=O carbon inductively
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ADDITION OF H 2 O:
HYDRATION
The addition of water to an aldehyde
or a ketones results in the formation
of a hydrate.
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NUCLEOPHILIC
ADDITION OF H 2 O:
HYDRATION
A hydrate is a molecule with two OH
groups bonded to the same carbon.
Eg:
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MECHANISM FOR ACID CATALYZED HYDRATE
FORMATION
1)Water, acting as a nucleophile, is attracted to the
partially positive carbon of the carbonyl group, generating
an oxonium ion. (eg)
2) The oxonium ion liberates a hydrogen ion that is
picked up by the oxygen anion in an acid-base reaction. (eg)
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MECHANISM FOR ACID CATALYZED HYDRATE
FORMATION
 Small amount of acids and bases catalyze this reaction. This occurs
because the addition of acid causes a protonation of the oxygen of
the carboyl group, leading to the formation of a full positive charge
on the carbonyl carbon, making the carbon a good nucleus. Adding
hydroxyl ions changes the nucleophile from water ( a weak
nucleophile) to a hydroxide ion ( a strong nucleophile). Ketones
usually do not form stable hydrates.
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MECHANISM FOR ACID CATALYZED HYDRATE
FORMATION
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A D D I T I O N O F WA T E R TO F O R M
HYDRATES (GEM-DIOS)
 It has been demonstrated that water, in the presence of an acid or a
base, ass rapidly to the carbonyl function of aldehydes and ketones
establish a reversible equilibrium with a hydrate (menial-diol or gemdiol).
 The word germinal or gem comes from the Latin word for twin.
 Eg:
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NUCLEOPHILIC ADDITION OF
H 2 O: HYDRATION
Aldehydes and ketones react with water to yield 1,1diols (geminal (gem) diols)
 Hydration is reversible: a gem diol can eliminate water
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REVERSIBILITY OF THE
REACTION
 Isolation of gem-diols is difficult because the reaction is
reversibly. Removal of the water during a reaction can cause
the conversation of a gem-diol back to the corresponding
carbonyl.
 Eg:
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MECHANISM OF
GEM-DIOL FORMATION
 The mechanism is catalyzed by the addition of an acid or
base. Basic conditions speed up the reaction because hydroxide
is a better nucleophilic than water. Acidic conditions speed up
the reaction because the protonated carbonyl is more
electrophilic.
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MECHANISM OF
GEM-DIOL FORMATION
Under Basic Condition
1) Nucleophilic attack by the hydroxide
2) Protonation of the alkoxide
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BASE-CATALYZED ADDITION OF
WATER
Addition of water
is catalyzed by both
acid and base
The basecatalyzed hydration
nucleophile is the
hydroxide ion,
which is a much
stronger nucleophile
than water
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MECHANISM OF
GEM-DIOL FORMATION
Under Acidic Conditions
1)
Protonation of the carbonyl
2)
Nucleophilic attack by water
3)
Deprotonation
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ACID-CATALYZED ADDITION OF
WATER
Protonation of
C=O makes it
more electrophilic
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Examples
1) Draw the expected products of
the following reactions
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REACTIONS OF
ALDEHYDES AND
KETONES
 Relative Reactivity
 Nucleophilic Addition Reactions
 Reduction Of Aldehydes and Ketones
-
To Hydrocarbons
-
Using Hydrides to give Alcohols
 Using Carbon Nucleophiles
-
Formation of Cyanohydrins
-
Reactions of Grignard Reagents (Organometallic Reagents)
-
The Wittig Reaction
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REACTION OF ALDEHYDES
AND KETONES
Reduction of Aldehydes and Ketones
1) To Hydrocarbons
 Reduction of hydrocarbons: Wolff-Kishner
Reduction (basic conditions)
2) Using Hydrides to give Alcohols
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REDUCTION OF ALDEHYDES
A N D K E TO N E S
1) To hydrocarbones;
Reduction of Hydrocarbons: Wolff-Kishner Reduction (basic
conditions)
 NH2NH2/KOH/ethylene glycol reduces the C=O into
–CH2-
(convert carbonyl functionalities into methylene groups)
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WO L F F - K I S H N E R M E C H A N I S M
 Reaction of aldehydes or ketones with hydrazine produces a
hydrazone :
 Reaction with a base and heat converts a hydrazone to an alkene:
 Both reactions together produces the Wolff-Kishner Reduction:
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:
MECHANISM OF THE WOLFF KISHNER REDUCTION
1) Deprotonation of Nitrogen
2) Protonation of the Carbon
3) Deprotonation of Nitrogen
4) Protonation of Carbon
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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
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TH E WOLFF –K ISH N ER R EACTION:
EXA MPLES
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REDUCTION OF ALDEHYDES
A N D K E TO N E S
2) Hydride Reduction (to alcohols)
- Reactions usually in Et2O or THF
followed by H3O+ work-ups
- Eg:
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HYDRIDE ADDITION
Convert C=O to CH-OH
LiAlH4 and NaBH4 react as donors of
hydride ion
Protonation after addition yields the alcohol
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Reactions of Carbonyl Compounds
with Hydride Ion
Hydronium ion
Hydride ion
Alkoxide
ion
Ketone or aldehyde is reduced to primary
or secondary alcohol
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Sodium borohydride –NaBH4
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USING CARBON NUCLEOPHILES
(REDUCTIONOF ALDEHYDES & KETONES)
1) Formation of Cyanohydrins
2) Reactions of Grignard reagents / Organometallic
Reagents
3) The Wittig Reaction
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NUCLEOPHILIC ADDITION OF HCN :
CYANOHYDRIN FORMATION
Using carbon Nucleophiles
1) Formation of Cyanohydrins
 Cyanide adds to aldehydes and ketones to give a cyanohydrin
 The reaction is usually carried out using NaCN or KCN with HCl
 HCN is a fairly weak acid, but very toxic
 The reaction is useful since the cyano group can be converted into
other useful functional groups (-CO2H or –CH2NH2)
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NUCLEOPHILIC ADDITION OF
CYANIDE TO AN ALDEHYDE
 Step 1:
The nucleophilic C in the cyanide adds to the electrophilic C in the polar
carbonyl group, electrons from the C=O move to the electronegative O creating
an intermediate alkoxide.
 Step 2:
An acid/base reactions. Protonation of the alkoxide oxygen creates the
cyanohydrin product.
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NUCLEOPHILIC ADDITION OF
GRIGNARD REAGENTS AND
HYDRIDE REAGENTS:
A L C O H O L F O R M AT I O N
Using carbon Nucleophiles
2) Reactions of Grignard reagents /
Organometallic Reagents
Grignard reagents react with aldehydes,
ketones, and carboxylic acid derivatives
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R E A C T I O N S O F G R I G NA R D
REAGENTS
 Grindard reagents react with the carbonyl group, C=O, in aldehydes or ketons
to give alcohols
 The substituents on the carbonyl dictate the nature of the product alcohol
 Addition to methanal (formaldehyde) gives primary alcohols
 Addition to other aldehydes gives secondary alcohols
 Addition to ketones gives tertiary secondary alcohols
 The acidic work-up converts an intermediate metal alkoxide salt into the
desired alcohol via a simple acid base reaction.
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Formation of a New Carbon–Carbon
Bond Using Grignard Reagents
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REACTIONS OF GRIGNARD REAGENTS
Reactions of RLi and RMgX with aldehydes and ketones
• Reactions usually in Et2O or THF followed by H3O+ workups.
• Eg:
Treatment of aldehydes or ketones with Grignard reagents
yields an alcohol
• Nucleophilic addition of the equivalent of a carbon anion, or
carbanion. A carbon–magnesium bond is strongly polarized,
so a Grignard reagent reacts for all practical purposes as
R :  MgX +.
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MECHANISM OF ADDITION OF
G R I G NA R D R E A G E N T S
 NUCLEOPHILIC ADDITION OF RLi OR RMgX TO AN ALDEHYDE
 Step 1 :
The nucleophilic C in the Grignard Reagent adds to the electrophilic C in the
polar carbonyl group, electrons from the C=O move to the electronegative O
creating an intermediate metal alkoxide complex.
 Step 2 :
This is the work-up step, a simple acid/base reaction. Protonation of the alkoxide
oxygen creates the alcohol product from the intermediate complex.
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MECHANISM OF ADDITION OF
GRIGNARD REAGENTS
Complexation of
C=O by Mg2+,
Nucleophilic
addition of R : ,
protonation by
dilute acid yields the
neutral alcohol
Grignard
additions are
irreversible because
a carbanion is not a
leaving group
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Grignard reagents are used to prepare alcohols:
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Nucleophilic Addition of Phosphorus Ylides:
Using carbon Nucleophiles
3) The Wittig Reaction
 The Wittig reactions is an important method for the formation of alkanes
 The double bond forms specially at the location of the original aldehyde or ketone
 Ylides are naturel molecules but have +ve and –ve centers on adjacent atoms that are
connected by a s bond
 The ylids is prepared via a 2 step process:
An SN2 reaction between triphenyl phosphine and an alkyl halide followed by
treatment with a strong base as an Grignard reagent.
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NUCLEOPHILIC ADDITION OF PHOSPHORUS YLIDES:
THE WITTIG REACTION
The sequence converts C=O  C=C
A phosphorus ylide adds to an aldehyde or ketone to
yield a dipolar intermediate called a betaine
The intermediate spontaneously decomposes through a
four-membered ring to yield alkene and
triphenylphosphine oxide, (Ph)3P=O
An ylide
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MECHANISM OF THE
WITTIG REACTION
Step 1:
The nucleophilic C of the ylid Wittig reagent adds to the electrophilic C in the
polar carbonyl group, electrons from the C=O pi bond are used to form a σ bond
to the +ve P atom. This creates a cyclic intermeiate called an oxaphosphate.
Step 2:
Decomposition of the intermediate by breaking the C-P and C-O σ bonds leads
to the formation of the C=C π bond of the alkene and triphenyl phosphine
oxide.
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MECHANISM
OF THE
WITTIG
REACTION
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N U C L E O P H I L I C A D D I T I O N O F A M I N ES:
I M I N E A N D E N A M I N E F O R M AT I O N
RNH2 adds to C=O to form imines, R2C=NR (after loss of
HOH)
R2NH yields enamines, R2NCR=CR2 (after loss of HOH)
(ene + amine = unsaturated amine)
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MECHANISM OF
F O R M AT I O N O F
IMINES
Primary amine adds to
C=O
Proton is lost from N and
adds to O to yield a neutral
amino alcohol
(carbinolamine)
Protonation of OH
converts into water as the
leaving group
Result is iminium ion,
which loses proton
Acid is required for loss of
OH – too much acid blocks
RNH2
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ENAMINE
FORMATION
After addition
of R2NH,
proton is lost
from adjacent
carbon
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IMINE / ENAMINE EXAMPLES
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NUCLEOPHILIC ADDITION OF
ALCOHOLS: ACETAL FORMATION
 Alcohols are weak nucleophiles but acid promotes addition forming
the conjugate acid of C=O
 Addition yields a hydroxy ether, called a hemiacetal (reversible); further
reaction can occur
 Protonation of the OH and loss of water leads to an oxonium ion,
R2C=OR+ to which a second alcohol adds to form the acetal
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ACETAL
FORMATION
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