Aldehydes

1
Chapter 19
Aldehydes Ketones Nucleophilic Addition
Reactions
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Aldehyde Nomenclature

• Find the longest chain that contains the
  aldehyde.
• The suffix al replaces the e of the
  corresponding alkane.
• The carbonyl carbon receives the lowest number.
• Branches are named using the IUPAC system
• Complex aldehydes (-CHO is attached to a ring)
  use the suffix -carbaldehyde

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Examples
2-Ethyl-4-methylpentanal
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Common Names of Aldehydes
5
Ketone Nomenclature

• Find the longest chain that contains the ketone
  (it MUST NOT BE at the end)
• Use the base hydrocarbon name drop the e and
  replace with one.
• The carbonyl group has to be assigned the lowest
  possible number.
• In complex molecules, the carbonyl group can be
  named as a prefix with the term oxo-

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Refering as Subsituents

• RCO-
  Acyl
• CH3CO-
  Acetyl
• -CHO
  Formyl
• C6H5CO-
  Benzoyl
• In complex molecules, the carbonyl group can be
  named as a prefix with the term oxo-
• methyl 3-oxohexanoate

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Ketone Nomenclature Examples
3-Hexanone
4-Hexen-2-one
2,4 Hexanedione
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Common Names of Some Ketones
Acetone
Acetophenone
Benzophenone
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Synthesis of Aldehydes

• Oxidation of 1 alcohols

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Synthesis of Aldehydes

• Oxidative cleavage of alkenes w/ O3, Zn, CH3COOH

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Synthesis of Aldehydes

• Partial reduction of certain carboxylic acid
  derivatives

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Synthesis of Ketones

• Oxidation of 2 alcohols w/ PCC and base

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Synthesis of Ketones

• Ozonolysis of alkenes, if one of the unsaturated
  carbon atoms is disubstituted.

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Synthesis of Ketones

• Friedel-Crafts acylation aryl
  ketones

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Synthesis of Ketones

• Hydration of terminal alkynes methyl
  ketones

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Synthesis of Ketones continue
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Synthesis of Ketones

• From certain carboxylic acid derivatives using a
  Gilman reagent (R2Cu-Li)

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Oxidation of Aldehydes and Ketones

• aldehydes- readily oxidized to form carboxylic
  acids
• Ketones-inert but can be with hot alkaline KMnO4
• REASON aldehydes have a CHO proton that can be
  removed during oxidation ketones dont.
• Oxidizing agents KMnO4
• HNO3
• CrO3 in acidic conditions
• Tollens reagent (Ag2O) in aqueous
  ammonia

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Aldehyde Oxidation

• Occur through intermediate 1,1-diols, or hydrates.

H2O
An aldehyde
A hydrate
A carboxylic acid
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Mechanism of Aldehyde Oxidation
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Mechanism of Aldehyde Oxidation continue
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Ketone Oxidation

• Inert to most oxidizing agents
• Ketones undergo slow cleavage when treated with
  hot alkaline KMnO4

1.
2.
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Nucleophilic Addition Rxns of Aldehydes and
Ketones

• Nucleophile attacks the electrophilic CO carbon
  from a direction 45 to the plane of the
  carbonyl group.
• At the same time Rehybridization of the
  carbonyl carbon from sp2 to sp3 occurs, an
  electron pair from the carbon-oxygen double bond
  moves toward the electronegative oxygen atom, and
  a tetrahedral alkoxide ion intermediate is
  produced.

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Attacking Nucleophiles

• Can be negatively charged or neutral at the
  reaction site

• Negatively charged Nucleophiles
• HO- (hydroxide ion)
• H- (hydride ion)
• R3C- (a carbanion)
• RO- (an alkoxide ion)
• CN- (cyanide ion)

• Neutral Nucleophiles
• H2O (water)
• ROH (an alcohol)
• H3N (ammonia)
• RNH2 (an amine)

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Nucleophilic Addition Rxns of Aldehydes and
Ketones

• Formation of an alcohol

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Nucleophilic Addition Rxns of Aldehydes and
Ketones

• Elimination of the carbonyl oxygen atom at HO-
  or H2O to give a product with CNu double bond.

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Relative Reactivity of Aldehydes and Ketones

• Reactivity in nucleophilic addition rxns
• Aldehydes gtgtgt ketones
• aliphatic aldehydes gtgtgt aromatic aldehydes

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Steric Reason why Aldehydes are More Reactive
than Ketones

• nucleophile is able to approach aldehydes more
  readily because it only has 1 large substituent
  bonded to the CO carbon, vs. 2 in ketones.
• transition state for the aldehyde rxn is
  therefore less crowded and has lower energy.
• aldehyde
  ketone

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Electronic Reason why Aldehydes are More Reactive
than Ketones

• greater polarization of aldehyde carbonyl group
• aldehyde is more electrophilic and more reactive
  than ketones.

2carbocation (more stable, less
reactive)

Ketone (more stabilization of ?, less
reactive)
1 carbocation (less stable,
more reactive)
Aldehyde (less stabilization of ?, more
reactive)
?-
?-
?
?
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Why aromatic aldehydes gtgtgt aliphatic aldehydes

• The electon-donating resonance effect of the
  aromatic ring makes the carbonyl group less
  electrophilic than the carbonyl group of the
  aliphatic aldehyde.

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Why aromatic aldehydes gtgtgt aliphatic
aldehydesexample

• Comparing electrostatic potential maps of
  formaldehyde and benzaldehyde, shows that the
  carbonyl carbon atom is less positive in the
  aromatic aldehyde
• formaldehyde benzaldehyde

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Nucleophilic Addition of H2O Hydration

• Aldehydes and ketones react with water to yield a
  geminal diol. This hydration process is
  reversible.
• Nucleophilic addition of water is catalyzed by
  acid and base.
• Base-catalyzed

• Acid-catalyzed

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Nucleophilic Addition of HCN Cyanohydrin
Formation

• Aldehydes and unhindered ketones react with HCN
  to yield cyanohydrins. This formation is
  reversible and base-catalyzed.

• Cyanohydrins formation is unusual due to the
  addition of protic acid to a carbonyl group,
  but useful because of further chemistry.
• Reduced with LiAlH4, yielding primary amine.
• Hydrolyzed with hot aqueous acid, yielding
  carboxylic acid.

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Nucleophilic Addition of Grignard Hydride
Reagents Alcohol Formation

• Grignard reagents R-MgX, strongly polarized
  reacts with an acid-base behavior.
  Nucleophilic addition of a carbanion to an
  aldehyde or ketone, followed by protonation of
  alkoxide intermediate, yields an alcohol.

• Addition of hydride ion, from LiAlH4 or NaBH4,
  and water or aqueous acid yields an alcohol.

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Nucleophilic Addition of AminesImine and
Enamine Formation

• Difference between imine and enamine is the CN
  bond and CC bond.

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Nucleophilic Addition of AminesMechanism of 1º
amines forming Imine
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Nucleophilic Addition of AminesMechanism of 2º
amines forming Enamine
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Nucleophilic Addition of HydrazineWolff-Kishner
Reaction

• Addition of hydrazine converts aldehyde/ketone to
  an alkane. An intermediate hydrazone forms,
  followed by base catalyzed double bond migration,
  loss of N2 gas, finally protonation yields an
  alkane.

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Nucleophilic Addition of Alcohols Acetal
Formation

• Acetals and Ketals are formed by reacting two
  equivalents of an alcohol with an aldehyde or
  ketone, in the presence of an acid catalyst.
• Hemiacetals and Hemiketals are formed by reacting
  only one equivalent of alcohol with the aldehyde
  or ketone in the presence of an acid catalyst.
  Further reaction with a second alcohol forms the
  acetal or ketal.
• A diol, with two OH groups on the same molecule,
  can be used to form cyclic acetals.
• All steps in acetal/ketal formation are
  reversible.

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• Acetal
  Ketal
• Hemiacetal
  Hemiketal

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Mechanism of Acetal Formation
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Nucleophilic Addition of Phosphorus Ylides The
Wittig Reaction

• Converts an aldehyde/ketone into an alkene.
• A phosphorus ylide(aka phosphorane),
  ,

• acts as the nucleophile to attack the
  carbonyl carbon
• and yields a four-membered ring, dipolar
  intermediate
• called the betaine.
• The betaine decomposes spontaneously to yield an
• alkene and a triphenylphosphine oxide.
• Can produce monosubstituted, disubstituted, and
  
• trisubstituted alkenes.

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Mechanism of the Witting Reaction
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The Canizzaro Reaction

• Requires two equivalents of an aldehyde and a
  heated aqueous base.
• Produces a 11 mixture of carboxylic acid and
  alcohol.
• Limited to aldehydes such as formaldehyde and
  benzaldehyde, which have no hydrogens on carbon
  next to carbonyl.
• Results in simultaneous oxidation and reduction,
  disproportionation.
• Steps
• 1. Nucleophillic addition of OH- to first
  aldehyde forms a tetrahedral
• intermediate.
• 2. Tetrahedral intermediate then expels the
  hydride ion as a leaving
• group.
• 3. The second aldehyde picks up the hydride
  ion.
• 4. Oxidation of second product yields the
  acid while reduction of
• the first product yields an alcohol.

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Mechanism of Cannizzaro Reaction
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Conjugate Nucleophilic Addition to
alpha,beta-Unsaturated Aldehydes and Ketones

• Direct addition (aka 1,2 addition) occurs when a
  nucleophile attacks the carbon in the carbonyl
  directly.
• Conjugate addition (aka 1,4 addition) occurs when
  the nucleophile attacks the carbonyl indirectly
  by attacking the second carbon away from the
  carbonyl group, called the beta carbon, in an
  unsaturated aldehyde or ketone.
• Conjugate addition reactions form an initial
  product called an enolate, which is protonated on
  the carbon next to the carbonyl, the alpha
  carbon, to give the final saturated
  aldehyde/ketone product.
• Conjugate addition can be carried out with
  nucleophiles such as primary amines, secondary
  amines, and even alkyl groups like in
  organocopper reactions.
• It is the carbonyl that activates the conjugated
  CC double bond for addition which would
  otherwise not react.

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Conjugate (1,4) addition mechanism
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Some Biological Nucleophilic Addition Reactions

• Living organisms use nucleophilic addition
  reactions involving aldehydes and ketones in
  nature.

• Examples
• -In Metabolism Breakdown of alanine
• -In Defense Secretion of poison by the
  millipede

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A Nucleophilic Addition Reaction Metabolism

• The human body uses the amino acid alanine to
  react with pyridoxal phosphate, an aldehyde, in a
  metabolic reaction to produce an imine.

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A Nucleophilic Addition Reaction Defense

• Apheloria corrugata, a millipede, discharges
  poisonous HCN at attackers.
• The millipede secretes the mandelonitrile
  molecule and another enzyme that breaks it down
  into benzaldeyde and HCN.

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Spectroscopy of Aldehydes and Ketones

• Aldehydes and Ketones show characteristic
  absorptions in Infrared Spectroscopy, Nuclear
  Magnetic Resonance Spectroscopy, and Mass
  Spectrometry.

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Infrared Spectroscopy of Aldehydes/Ketones

• Aldehydes/Ketones show a strong CO bond
  absorption at 1660-1770 cm-1.
• Aldehydes show two characteristic absorptions in
  the
• 2720-2820 cm-1 range.
• Conjugation of an aldehyde lowers absorption
  position.
• Angle strain in the carbonyl group of a ketone
  caused by reducing the ring size of cyclic
  ketones raises absorption position.

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IR of Benzaldehyde and Cyclohexanone
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Nuclear Magnetic Resonance of Aldehydes/Ketones

• H NMR

• Aldehyde protons absorb near 10 ppm.
• Hydrogens next to the carbonyls of aldehydes and
  ketones are slightly deshielded and absorb near 2
  to 2.3 ppm.
• Methyl ketones show a sharp three-proton singlet
  near 2.1 ppm.

• Aldehyde and ketone carbonyl carbons show
  absorptions between 190 to 215 ppm.
• Saturated aldehyde or ketone carbons absorb in
  the 200 to 215 ppm range.
• Aromatic and a,b-unsaturated carbonyl carbons
  absorb in the 190 to 200 ppm range.

• C NMR

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H NMR of Acetaldehyde
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Mass Spectrometry of Aldehydes/Ketones

• Alipatic aldehydes and ketones that have
  hydrogens on their gamma carbon atoms undergo
  McLafferty rearrangement.

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Mass Spectrum of 5-methyl-2-hexanone