CH 19: Aldehydes and Ketones

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CH 19 Aldehydes and Ketones

• Renee Y. Becker
• Valencia Community College
• CHM 2211

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Some Generalizations About Carbonyl Compounds

• The most important functional group in organic
  chemistry.

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Some Generalizations About Carbonyl Compounds

• carbonyl compounds are planar about the double
  bond with bond angles ? 120? due to the sp2
  hybridized carbon.
• Many types of carbonyl compounds have significant
  dipole moments.
• The polarity of the C-O bond plays a significant
  role in the reactivity of carbonyl compounds.

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Aldehydes and Ketones
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Aldehydes and Ketones

• Due to the polarity of the carbonyl C-O bond,
  aldehydes and ketones have higher BPs than
  alkanes with similar molecular weights.
• The lack of H-bonding hydrogens, results in lower
  BPs than similar alcohols.

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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
• If the ?CHO group is attached to a ring, use the
  suffix carbaldehyde.

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Naming Aldehydes
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Naming Aldehydes
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Example 1 Name
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Example 2 Draw

• 3-Methylbutanal
• 3-Methyl-3-butenal
• cis-3-tert-Butylcyclohexanecarbaldehyde

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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 group
• Numbering begins at the end nearer the carbonyl
  carbon

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Naming Ketones
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Naming Ketones

• Ketones with Common Names

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Ketones and Aldehydes as Substituents

• The RCO as a substituent is an acyl group is
  used with the suffix -yl from the root of the
  carboxylic acid
• CH3CO acetyl CHO formyl C6H5CO benzoyl

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Ketones and Aldehydes as Substituents

• 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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Example 3 Name
1.
3.
4.
2.
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Example 4 Draw

• 4-Chloro-2-pentanone
• P-bromoacetophenone
• 3-ethyl-4-methyl-2-hexanone

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Preparation of Aldehydes

• Oxidize primary alcohols using pyridinium
  chlorochromate

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Preparation of Aldehydes

• Oxidation of alkenes with a vinylic hydrogen

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Preparation of Aldehydes

• The partial reduction of certain carboxylic acid
  derivatives. (esters)

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Example 5

• How would you prepare pentanal from the
  following
• 1. 1-Pentanol
• 1-Hexene

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Preparing Ketones

• Oxidation of secondary alcohols

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Preparing Ketones

• Oxidation of alkenes if one unsaturated carbon is
  disubstituted

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Preparing Ketones

• Friedel-Crafts acylation of aromatic compounds
  with an acid chloride.

Occurs only once!
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Preparing Ketones

• Hydrations of terminal alkynes
• Methyl ketone synthesis
• Hg2 catalyst

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Example 6

• How would you carry out the following reactions?
  More than 1 step might be necessary.
• 1. 3-Hexyne ? 3-Hexanone
• 2. Benzene ? m-Bromoacetophenone
• 3. Bromobenzene ? Acetophenone

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Reactions of Aldehydes and Ketones

• Oxidation reactions
• Nucleophilic addition reactions
• Conjugate nucleophilic addition reactions

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Oxidation of Aldehydes

• Jones Reagent (preferred)
• Preferred over other oxidation reagents due to
  Room temp. reaction with high yields
• Run under acidic conditions (con)
• Will react with CC and any acid sensitive
  functionality

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Oxidation of Aldehydes

• Tollens reagent
• For use with CC double bonds

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Oxidation of Ketones

• Ketones are resistant toward oxidation due to the
  missing hydrogen on the carbonyl carbon
• Treatment of ketones with hot KMnO4 will cleave
  the C-C bond adjacent to the carbonyl group

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Nucleophilic Addition Reactions of Aldehydes and
Ketones

• Nu- approaches 45 to the plane of CO and adds
  to C
• A tetrahedral alkoxide ion intermediate is
  produced

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Nucleophiles

• Nucleophiles can be negatively charged ( Nu?)
  or neutral ( Nu) at the reaction site
• The overall charge on the nucleophilic species is
  not considered

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Nucleophilic Addition Reactions
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Relative Reactivity of Aldehydes and Ketones

• Aldehydes are generally more reactive than
  ketones in nucleophilic addition reactions
• The transition state for addition is less crowded
  and lower in energy for an aldehyde (a) than for
  a ketone (b)

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Electrophilicity of Aldehydes and Ketones

• Aldehyde CO is more polarized than ketone CO
• As in carbocations, more alkyl groups stabilize
  character
• Ketone has more alkyl groups, stabilizing the CO
  carbon inductively

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Reactivity of Aromatic Aldehydes

• Aromatic aldehydes are less reactive in
  nucleophilic addition than straight chain
  aldehydes
• Due to electron-donating resonance effect of
  aromatic ring
• Makes carbonyl group less electrophilic

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Nucleophilic Addition of H2O Hydration

• Aldehydes and ketones react with water to yield
  1,1-diols (geminal (gem) diols)
• Hyrdation is reversible a gem diol can eliminate
  water

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Relative Energies

• Equilibrium generally favors the carbonyl
  compound over hydrate for steric reasons
• Acetone in water is 99.9 ketone form
• Exception simple aldehydes
• In water, formaldehyde consists is 99.9 hydrate

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Acid Base-Catalyzed Addition of Water

• Addition of water is catalyzed by both acid and
  base
• The base-catalyzed hydration nucleophile is the
  hydroxide ion, which is a much stronger
  nucleophile than water
• Acid-Catalyzed Addition of Water
• Protonation of CO makes it more electrophilic

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Mechanism 1 Base catalyzed hydration of an
aldehyde/ketone
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Mechanism 2 Acid catalyzed hydration of an
aldehyde/ketone
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Addition of H-Y to CO

• Reaction of CO with H-Y, where Y is
  electronegative, gives an addition product
  (adduct)
• Formation is readily reversible

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Nucleophilic Addition of HCN Cyanohydrin
Formation

• Aldehydes and unhindered ketones react with HCN
  to yield cyanohydrins, RCH(OH)C?N

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Mechanism of Formation of Cyanohydrins

• Addition of HCN is reversible and base-catalyzed,
  generating nucleophilic cyanide ion, CN
• Addition of CN? to CO yields a tetrahedral
  intermediate, which is then protonated
• Equilibrium favors adduct

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Mechanism 3 Formation of Cyanohydrins
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Uses of Cyanohydrins

• Nitriles can be reduced with LiAlH4 to yield
  primary amines

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Uses of Cyanohydrins

• Nitriles can be hydrolyzed with hot aqueous acid
  to yield carboxylic acids

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Nucleophilic Addition of Grignard Reagents and
Hydride Reagents Alcohol Formation

• Treatment of aldehydes or ketones with Grignard
  reagents yields an alcohol
• Nucleophilic addition of the equivalent of a
  carbon anion, or carbanion. A carbonmagnesium
  bond is strongly polarized, so a Grignard reagent
  reacts for all practical purposes as R ? MgX .

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Mechanism of Addition of Grignard Reagents

• Complexation of CO 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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Mechanism 4 Addition of Grignard Reagents
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Hydride Addition

• Convert CO to CH-OH
• LiAlH4 and NaBH4 react as donors of hydride ion
• Protonation after addition yields the alcohol

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Nucleophilic Addition of Amines Imine and
Enamine Formation

• RNH2 (primary amines) adds to CO to form imines,
  R2CNR (after loss of HOH)
• R2NH (secondary amines) yields enamines,
  R2N?CRCR2 (after loss of HOH) (ene amine
  unsaturated amine)

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Mechanism of Formation of Imines

• Primary amine adds to CO
• 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

Note that overall reaction is substitution of RN
for O
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Mechanism 5 Imine Formation
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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

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Mechanism 6 Enamine Formation
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Nucleophilic Addition of Hydrazine The
WolffKishner 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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Mechanism 7 The WolffKishner Reaction
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Nucleophilic Addition of Alcohols Acetal
Formation

• Alcohols are weak nucleophiles but acid promotes
  addition forming the conjugate acid of CO
• 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, R2COR to which a second alcohol
  adds to form the acetal

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Uses of Acetals

• Acetals can serve as protecting groups for
  aldehydes and ketones
• It is convenient to use a diol, to form a cyclic
  acetal (the reaction goes even more readily)

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Nucleophilic Addition of Phosphorus Ylides The
Wittig Reaction

• The sequence converts CO is to CC
• 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)3PO
• Formation of the ylide is shown below

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Mechanism 8 The Wittig Reaction
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Uses of the Wittig Reaction

• Can be used for monosubstituted, disubstituted,
  and trisubstituted alkenes but not
  tetrasubstituted alkenes The reaction yields a
  pure alkene of known structure
• For comparison, addition of CH3MgBr to
  cyclohexanone and dehydration with, yields a
  mixture of two alkenes

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The Cannizaro Reaction

• The adduct of an aldehyde and OH? can transfer
  hydride ion to another aldehyde CO resulting in
  a simultaneous oxidation and reduction
  (disproportionation)

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Conjugate Nucleophilic Addition to
?,b-Unsaturated Aldehydes and Ketones

• A nucleophile can add to the CC double bond of
  an ?,b-unsaturated aldehyde or ketone (conjugate
  addition, or 1,4 addition)
• The initial product is a resonance-stabilized
  enolate ion, which is then protonated

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Conjugate Addition of Amines

• Primary and secondary amines add to ?,
  b-unsaturated aldehydes and ketones to yield
  b-amino aldehydes and ketones

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Conjugate Addition of Alkyl Groups Organocopper
Reactions

• Reaction of an ?, b-unsaturated ketone with a
  lithium diorganocopper reagent
• Diorganocopper (Gilman) reagents from by reaction
  of 1 equivalent of cuprous iodide and 2
  equivalents of organolithium
• 1?, 2?, 3? alkyl, aryl and alkenyl groups react
  but not alkynyl groups

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Gilman Reagent
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Mechanism of Alkyl Conjugate Addition

• Conjugate nucleophilic addition of a
  diorganocopper anion, R2Cu?, an enone
• Transfer of an R group and elimination of a
  neutral organocopper species, RCu

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Example 7