Aldehydes and Ketones

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Aldehydes and Ketones

• Structure and properties
• Nomenclature
• Synthesis (some review)
• Reactions (some review)
• Spectroscopy mass spec, IR, NMR

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Structure and properties
Aldehydes and ketones are the simplest carbonyl
containing compounds.
3
Structure and properties
The carbonyl carbon and oxygen are sp2 hybridized.
4
Structure and properties
The carbon oxygen double bond is very polarized.
The dipole moments of aldehydes and ketones are
larger than most alkyl halides and ether.
u 2.7 D
u 2.9 D
u 1.9 D
The high polarization of the carbonyl is due to
the electronegativity of oxygen and the
separation of charge in the resonance form.
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Structure and properties
London dispersion
Dipole-Dipole
Hydrogen bonding
The large polarization of the carbonyl functional
group produces dipole-dipole interaction between
the molecules of aldehydes and ketones.
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Structure and properties
Hydrogen bonding does not occur between aldehyde
and ketone molecules. Hydrogen bonding can occur
with other molecules such as water, alcohols and
amines.
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Solubility

• Soluble in 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.
  Solubility does decrease with longer chain length
  (gt 4-5 carbons).

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Naming Ketones (IUPAC)
Replace -e with -one. Indicate the position of
the carbonyl with a number. For diones, dont
drop the final e. Just add dione. Number the
chain so that carbonyl carbon has the lowest
number. For cyclic ketones the carbonyl carbon
is assigned the number 1.
-CHO gt RCOR gt R-OH gt R-NH2 gt CC gt CC
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Naming Ketones (IUPAC)
3-methyl-2-butanone 3-methylbutan-2-one
3-bromocyclohexanone
4-hydroxy-3-methyl-2-butanone 4-hydroxy-3-methylbu
tan-2-one
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Naming Ketones (IUPAC)
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Common Names for Ketones

• Named as alkyl attachments to -CO.
• Use Greek letters instead of numbers. (alpha,
  beta and gamma)

methyl isopropyl ketone
a-bromoethyl isopropyl ketone

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Common Ketones to know
Acetone methyl ethyl
ketone (MEK)
Acetophenone propiophenone
benzophenone
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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
3-methylpentanal
2-cyclopentenecarbaldehyde cyclopent-2-en-1-carbal
dehyde
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Examples
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Name as Substituent

• On a molecule with a higher priority functional
  group, CO is oxo- and -CHO is formyl.
• Aldehyde priority is higher than ketone.

3-methyl-4-oxopentanal
3-formylbenzoic acid
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Aldehyde Common Names

• Use the common name of the acid.
• Drop -ic acid and add -aldehyde.
• 1 C formic acid, formaldehyde
• 2 Cs acetic acid, acetaldehyde
• 3 Cs propionic acid, propionaldehyde
• 4 Cs butyric acid, butyraldehyde.
  
  

?-bromobutyraldehyde 3-bromobutanal
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Common Aldehyde
Formaldehyde acetaldehyde
propionaldehyde butyraldehyde
Benzaldehyde p-tolualdehyde
2-naphthaldehyde
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Common Aldehyde
Common forms of aldehydes. Formalin is a 40
solution of formaldehyde in water. There are
two dry forms of formaldehyde the cyclic trimer
trioxane and paraformaldehyde.
Trioxane paraformaldehyde
Heating these materials convert them to
formaldehyde.
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IR Spectroscopy

• Very strong CO stretch around 1710 cm-1.
• Conjugation lowers CO frequency to 1685-1690
  cm-1.
• Ring strain raises frequency.
• (Cycolpentanone 1745 cm-1, cycolpropanone 1810
  cm-1 )
• Additional C-H stretch for aldehyde two
  absorptions at 2710 cm-1 and 2810 cm-1.

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NMR Spectroscopy

• 1H
• Aldehyde protons are in the d 9-10 range.
• CH3 adjacent to a carbonyl singlet at d 2.1.
• CH2 adjacent to a carbonyl give multiple peaks at
  d 2.5.

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NMR Spectroscopy

• 13C
• Carbonyl carbon singlet in the 175-210 ppm range.
• Carbons alpha to the carbonyl are in the 30-40
  ppm range.

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1H NMR Spectroscopy
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13C NMR Spectroscopy
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Mass Spectroscopy
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Mass Spectroscopy
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Mass Spectroscopy
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Industrial Importance

• Acetone and methyl ethyl ketone are important
  solvents.
• Formaldehyde used in polymers like Bakelite?.
• Flavorings and additives like vanilla, cinnamon,
  artificial butter.

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Common aldehydes and Ketones
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Synthesis Review

• Oxidation
• 2? alcohol Na2Cr2O7 ? ketone
• 1? alcohol PCC ? aldehyde
• Ozonolysis of alkenes.

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Synthesis Review

• 2? alcohol Na2Cr2O7 ? ketone

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Synthesis Review

• 1? alcohol PCC ? aldehyde

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Synthesis Review

• Ozonolysis of alkenes.

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Synthesis Review

• Predict the products of the following reactions.

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Synthesis Review

• Friedel-Crafts acylation of aromatic rings
• Acid chloride/AlCl3 benzene ? ketone
• Gatterman-Koch
• CO HCl AlCl3/CuCl benzene ? benzaldehyde

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Synthesis Review
Predict the products.
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Synthesis Review
Predict the products.
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Synthesis Review

• Hydration of alkyne
• Use HgSO4, H2SO4, H2O a methyl ketone is
  obtained with a terminal alkyne.
• Use Sia2BH followed by H2O2 in NaOH for aldehyde.

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Synthesis Review

• Hydration of alkyne

Predict the products.
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Synthesis Review

• Hydration of alkyne to an aldehyde

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Synthesis Using 1,3-Dithiane

• Remove H with n-butyllithium.

• Alkylate with primary alkyl halide, then
  hydrolyze.

R-X is a primary halide or tosylate.
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Ketones from 1,3-Dithiane
After the first alkylation, the second H can
be removed using BuLi and the resulting anion
react with another primary alkyl halide. Giving
a ketone upon hydrolyze.
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Examples of using 1,3-Dithiane
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Ketones from Carboxylates

• Organolithium compounds attack the carbonyl and
  form a dianion.
• Neutralization with aqueous acid produces an
  unstable hydrate that loses water to form a
  ketone.

The reaction can be done by first treating with
one eq. of LiOH followed by a alkyl/aryl lithium
reagent. Consider what is happening in each step
(mechanistically how does the reaction work?).
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Ketones from Carboxylates
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Ketones from Nitriles

• A Grignard or organolithium reagent attacks the
  nitrile carbon.
• The imine salt is then hydrolyzed to form a
  ketone.

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Aldehydes from Acid Chlorides
A mild reducing agent can reduce an acid chloride
to an aldehyde.
What would happen if you used LAH?
Acid Chlorides are prepared by treating an acid
with thionyl chloride (SOCl2).
Show the synthesis of benzaldehyde from toluene.
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Ketones from Acid Chlorides
Treatment of an acid chloride with lithium
dialkylcuprate (R2CuLi) can also be used to
synthesize ketones.
Reagent preparation
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Ketones from Acid Chlorides
How it the lithium reagent made?
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Nucleophilic Addition
The addition of a nucleophile to the carbonyl
carbon is the most common reaction of aldehydes
and ketones.
Note The carbonyl carbon is an electrophilic
center.
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Nucleophilic Addition

• There two general types of addition reactions.
• Strong nucleophiles attack the carbonyl carbon,
  forming an alkoxide ion. The resulting alkoxide
  is then protonated to give an alcohol. (see
  previous slide)
• Weak nucleophiles attack a carbonyl if it has
  been protonated (acid conditions). Protonation
  of the carbonyl increases the reactivity of the
  carbonyl carbon toward nucleophilic attack. The
  final step is deprotonation of the nucleophile.

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Nucleophilic Addition
Strong nucleophile addition.
If the carbonyl carbon becomes a stereo center in
the product, both enantiomer are produced.
Weak nucleophile addition.
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Nucleophilic Addition

• Grignard reaction
• Grignard reagents add to aldehydes to give
  secondary alcohols and
• ketones to give tertiary alcohols. (one
  exception CH2O)

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Addition of Water hydration

• In acid, water is the nucleophile.
• In base, hydroxide is the nucleophile.
• Aldehydes are more electrophilic since they have
  fewer e--donating alkyl groups. (more reactive)

Classify the products?
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Addition of Alcohols
The addition of alcohols to the carbonyl is
similar to the addition of water.
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Mechanism

• The formation of acetals and ketals is acid
  catalyzed.
• Adding H to carbonyl makes it more reactive with
  weak nucleophile, ROH.
• The addition of a single alcohol produces a
  hemiacetal. Under the acidic reaction conditions
  water is loss, followed by addition of a second
  molecule of ROH forming the acetal.
• All steps are equilibrium processes (reversible)
  .

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Mechanism for Hemiacetal

• The acid catalyst protonates the carbonyl.
• Alcohol (a weak nucleophile) then adds to the
  carbonyl.
• Loss of H gives the hemiacetal.

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Hemiacetal to Acetal
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Cyclic Acetals

• Formation of cyclic acetals is used as a way of
  protecting the carbonyl group from under going
  nucleophilic attack in subsequent reactions. The
  protecting group can be remove by treatment with
  dilute acid.
• Cyclic acetals are made by reacting the aldehyde
  or ketone with a diol

Sugars commonly exist as acetals or hemiacetals.
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Acetals as Protecting Groups

• Hydrolyze easily in acid, stable in base.
• Aldehydes more reactive than ketones.

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Selective Reaction of Ketone

• React with strong nucleophile (base).
• Remove protective group.

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Selective Reaction of aldehydes and Ketones
How could the following synthesis be done.
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Addition of HCN

• CN- adds to the carbonyl group to give
  cyanohydrin.
• The order of reactivity is formaldehyde gt
  aldehydes gt ketones gtgt bulky ketones.

The nitrile group can be convert to an acid group
by acid hydrolysis.
a-hydroxy acid
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Formation of Imines

• The formation of an imine involves an initial
  nucleophilic attack by ammonia or a primary amine
  on the carbonyl carbon. Followed by subsequent
  loss of a water molecule.
• The CO becomes a CN-R group where R H, alkyl
  or aryl

imine also called a Schiff base when R is an
alkyl group
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Important N-containing derivatives
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Formation of N derivatives

• Loss of water is acid catalyzed, but acid
  deactivates the nucleophiles.
• NH3 H ?? NH4 (not nucleophilic).
• Optimum pH is around 4.5.

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Wittig Reaction

• This reaction involves the nucleophilic addition
  of a phosphorus ylides to the carbonyl carbon.
• The product of a Wittig reaction is an alkene.

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Phosphorus Ylides

• The ylide is prepared by first reacting
  triphenylphosphine with an unhindered alkyl
  halide (methyl or primary halide) to form a
  phosphonium salt.
• Treatment with butyllithium then abstracts a
  hydrogen from the carbon attached to phosphorus
  to produce the ylide.

ylide
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Mechanism for Wittig

• The negative C on ylide attacks the positive C of
  carbonyl to form a betaine.
• Oxygen combines with phosphine to form the
  phosphine oxide.

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Wittig Reaction

• Purpose are synthetic route for the preparation
  of the following compounds.

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Oxidation of Aldehydes
Aldehydes are easily oxidized to carboxylic acids.
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Tollens Test

• Tollens reagent is prepared by adding ammonia to
  a AgNO3 solution until the precipitate dissolves.
• Addition of Tollens reagent to a solution
  containing an aldehyde results in the formation
  of a silver mirror.

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Reduction Reagents

• Sodium borohydride, NaBH4, reduces CO, but not
  CC.
• Lithium aluminum hydride, LiAlH4, much stronger,
  difficult to handle.
• Hydrogen gas with catalyst also reduces the CC
  bond.

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Catalytic Hydrogenation

• Catalytic hydrogenation is widely used in
  industry.
• Raney nickel, finely divided Ni powder saturated
  with hydrogen gas.
• Pt and Rh also used as catalysts.

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Deoxygenation

• Reduction of CO to CH2
• Two methods
• Clemmensen reduction if molecule is stable in hot
  acid.
• Wolff-Kishner reduction if molecule is stable in
  very strong base.

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Clemmensen Reduction
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Wolff-Kisher Reduction

• Form hydrazone, then heat with strong base like
  KOH or potassium t-butoxide.
• Use a high-boiling solvent ethylene glycol,
  diethylene glycol, or DMSO.