Transcript Reactions of Aldehydes and Ketones – Nucleophilic Addition

REACTIONS OF ALDEHYDES AND KETONES – OXIDATION
Aldehydes are oxidized to carboxylic acids by various oxidizing agents.
Ketones oxidize with difficulty. They undergo slow cleavage with hot, alkaline KMnO4.
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B1. Addition of H– and R–
Treatment of an aldehyde or ketone with either NaBH4 or LiAlH4 followed by protonation forms
a 1° or 2° alcohol.
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B1. Addition of H– and R–
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B1. Addition of H– and R–
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.
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B1. Addition of H– and R–
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B2. Addition of CN–
Aldehydes and unhindered ketones react with HCN to yield cyanohydrins.
Because hydrogen cyanide is a toxic gas, best to use HCl and excess sodium cyanide.
Addition of HCN is reversible and base-catalyzed.
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B2. Addition of CN–
Cyanohydrins are important intermediates:
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REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B3. Reactions with Nitrogen Nucleophiles
Aldehydes and ketones react with a primary amine to form an imine. An imine is a compound
with a carbon–nitrogen double bond.
Aldehydes and ketones react with a secondary amine to form an enamine. Enamines have a
nitrogen atom bonded to a carbon–carbon double bond.
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B4. Addition of alcohols
The product formed when one equivalent of an alcohol adds to an aldehyde (ketone) is called a
hemiacetal (hemiketal). The product formed when a second equivalent of alcohol is added to an
aldehyde (ketone) is called an acetal (ketal).
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B4. Addition of alcohols
An alcohol is a poor nucleophile, so an acid catalyst is required for the reaction to take place at a
reasonable rate.
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B4. Addition of alcohols
Acetals or ketals (being ethers) are chemically resistant to action of bases, oxidizing and
reducing agents. However, they can be hydrolyzed back to aldehyde or ketone in acidic media.
Ketals are hard to isolate except when in a cyclic form.
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B4. Addition of alcohols
Acetals are useful protective groups
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B5. The Wittig Reaction
The nucleophilic addition of phosphorus ylide to an aldehyde or a ketone to form an alkene is
called a Wittig reaction. The sequence converts C=O is to C=C.
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B5. The Wittig Reaction
The phosphorus-containing reagent is called a phosphorane, and it belongs to a larger class of
compounds called ylides. An ylide is a compound with two oppositely charged atoms adjacent to
each other.
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B5. The Wittig Reaction
Wittig reagents are easily prepared by treating triphenylphosphine with an alkyl halide followed
by a strong base: (BuLi, NaH, NaNH2).
REACTIONS OF ALDEHYDES AND KETONES – NUCLEOPHILIC ADDITION REACTIONS
B5. The Wittig Reaction
Advantages of the Wittig reaction over other methods of preparing alkenes: position of double
bond is always clear, no rearrangement of carbon skeleton.
Complete the reactions. If no reaction occurs write N.R.
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C1. Acidity of the α Hydrogen
The α proton is quite acidic (pKa = 16-20)
The β proton is not acidic (pKa = 40-50)
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REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C1. Acidity of the α Hydrogen
The acidity of alpha proton is rationalized by considering resonance stabilization of conjugate
base, the enolate an ion.
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REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C1. Acidity of the α Hydrogen
The acidity of an α hydrogen, between two carbonyl groups, is even greater (pKa ≈ 9)
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REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C2. Keto-Enol Tautomerism
The negative charge of the enolate anion is distributed on both oxygen and carbon, the ion can
combine with a proton at either site.
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REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C2. Keto-Enol Tautomerism
The negative charge of the enolate anion is distributed on both oxygen and carbon, the ion can
combine with a proton at either site.
They are constitutional isomers = tautomers.
They interconvert rapidly in the presence of catalytic
amounts of acids or bases = tautomerization.
The keto form, generally, is heavily favored in the
equilibrium.
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REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C2. Keto-Enol Tautomerism
In β-dicarbonyls, the amount of enol tautomer present at equilibrium is much higher due to
resonance of conjugated system and intramolecular hydrogen bonding.
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How many acidic hydrogens does each of the molecules have? Draw structures for the enol
tautomers.
(a) cyclopentanone
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(b) acetyl chloride
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(c) ethyl acetate
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(d) propanal
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(e) acetic acid
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REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C3. Alpha-Halogenation
Aldehydes and ketones with at least one α-hydrogen react at the α-carbon with bromine,
chlorine, or iodine. The reaction is catalyzed by both acid and base.
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C3. Alpha-Halogenation
Mechanism of bromination of acetone in acetic acid:
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C3. Alpha-Halogenation
Mechanism of bromination of acetone in acetic acid:
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C3. Alpha-Halogenation
Mechanism of bromination of acetone in acetic acid:
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
Two molecules of an aldehyde or ketone (with α-hydrogens) react with each other in the
presence of a base to form a -hydroxy aldehyde or ketone.
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
Mechanism for the aldol addition:
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
Ketones are less susceptible than aldehydes to attack by nucleophiles, so aldol additions occur
more slowly with ketones. With ketones, the reaction proceeds well only if the product is
removed from the basic solution or reacts further by dehydration.
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
When heated in acidic or basic conditions, the product of an aldol addition reaction will undergo
elimination to produce unsaturation between the α and β positions: α,β-unsaturated aldehyde
or ketone.
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
Mechanism for dehydration:
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
The two-step process (aldol addition plus dehydration) is called an aldol condensation.
It is possible to carry out an aldol reaction between two different carbonyl compounds. Such
reactions are called crossed or mixed aldol reactions.
It requires that only one of the reactants is capable of forming an enolate (possesses an α-H).
REACTIONS OF ALDEHYDES AND KETONES – REACTIONS AT THE ALPHA CARBON
C4. The Aldol Addition
The products are very susceptible to dehydration when heated.
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SPECTROSCOPY
A. Mass Spectrometry
Cleavage of the bond between the carbonyl group and the  carbon yields a neutral radical and
an oxygen-containing cation.
SPECTROSCOPY
B. Infrared Spectroscopy
Aldehydes and ketones show a strong C=O peak at 1660 to 1770 cm–1
Aldehydes show two characteristic C–H absorptions in the 2720 to 2820 cm–1 range.
SPECTROSCOPY
C. Ultra-Violet Spectroscopy
UV-Vis active but not very useful
SPECTROSCOPY
D. 1H NMR
Aldehyde proton signals are at δ 10
Protons on the  carbon to the carbonyl group absorb at δ 2.0 to δ 2.5
SPECTROSCOPY
E. 13C NMR
C=O signal is at δ190 to δ215. No other kinds of carbons absorb in this range.
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