Transcript Chapter 19. Aldehydes and Ketones

Chapter 19. Aldehydes and
Ketones: Nucleophilic
Addition Reactions
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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Why this Chapter?
 Much of organic chemistry involves the
chemistry of carbonyl compounds
 Aldehydes/ketones are intermediates in
synthesis of pharmaceutical agents, biological
pathways, numerous industrial processes
 An understanding of their properties is essential
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19.1 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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19.1 Naming Aldehydes and Ketones
Methanal
(Common)
(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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Ketones and Aldehydes as 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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Learning Check:
 Name the following:
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Solution:
 Name the following:
2-methyl-3-pentanone
(ethyl isopropyl ketone)
2,6-octanedione
3-phenylpropanal
(3-phenylpropionaldehyde)
4-hexenal
Trans-2-methylcyclohexanecarbaldehyde
Cis-2,5-dimethylcyclohexanone
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19.2 Preparation of Aldehydes
Aldehydes
 Oxidation of 1o alcohols with pyridinium chlorochromate PCC
 Oxidative cleavage of Alkenes with a vinylic hydrogen with
ozone
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Preparation of Aldehydes
Aldehydes
 Reduction of an ester with diisobutylaluminum hydride
(DIBAH)
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Preparing Ketones
Ketones
 Oxidation of a 2° alcohol

Many reagents possible: Na2Cr2O7, KMnO4, CrO3

choose for the specific situation (scale, cost, and acid/base
sensitivity)
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Ketones from Ozonolysis
Ketones
 Oxidative cleavage of substituted Alkenes with ozone
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Aryl Ketones by Acylation
Ketones
 Friedel–Crafts acylation of an aromatic ring with an acid
chloride in the presence of AlCl3 catalyst
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Methyl Ketones by Hydrating Alkynes
Ketones
 Hydration of terminal alkynes in the presence of Hg2+ cat
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Preparation of Ketones
Ketones
 Gilman reaction of an acid chloride
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Learning Check:
 Carry out the following transformations:
3-Hexyne  3-Hexanone
Benzene  m-Bromoacetophenone
Bromobenzene  Acetophenone
1-methylcyclohexene  2-methylcyclohexanone
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Solution:
 Carry out the following transformations:
3-Hexyne  3-Hexanone
O
CH3
CH2
C C CH2
CH3
Hg(OAc)2,
CH3 CH2 C CH2 CH2 CH3
+
H 3O
Benzene  m-Bromoacetophenone
O
O
1) CH3
C Cl , AlCl3
Br
2) Br2, FeBr3
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Solution:
 Carry out the following transformations:
Bromobenzene  Acetophenone
Br
O
1) Mg in ether
O
2) CH3
C H
3) H3O+
4) PCC
1-methylcyclohexene  2-methylcyclohexanone
CH3
1) BH3
2) H2O2, NaOH
CH3
O
3) PCC
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19.3 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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19.4 Nucleophilic Addition Reactions of
Aldehydes and Ketones
 Nu-
approaches
75° to the
plane of C=O
and adds to C
 A tetrahedral
alkoxide ion
intermediate is
produced
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Nucleophiles
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Reactions variations
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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)
Aldehydes have one large substituent bonded to the C=O:
ketones have two
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Relative Reactivity of Aldehydes
and Ketones
 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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Reactivity of Aromatic Aldehydes
 Aromatic Aldehydes Less reactive in nucleophilic addition
reactions than aliphatic aldehydes

Electron-donating resonance effect of aromatic ring makes
C=O less reactive electrophile than the carbonyl group of
an aliphatic aldehyde
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19.5 Nucleophilic Addition of H2O:
Hydration
 Aldehydes and ketones react with water to yield 1,1-diols
(geminal (gem) diols)
 Hydration is reversible: a gem diol can eliminate water
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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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Acid-Catalyzed Addition of Water
 Protonation
of C=O
makes it
more
electrophilic
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Addition of H-Y to C=O
 Reaction of C=O with H-Y, where Y is electronegative,
gives an addition product (“adduct”)
 Formation is readily reversible
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19.6 Nucleophilic Addition of HCN:
Cyanohydrin Formation
 Aldehydes and unhindered ketones react with HCN to yield
cyanohydrins, RCH(OH)CN
 Addition of HCN is reversible and base-catalyzed,
generating nucleophilic cyanide ion, CN-
A cyanohydrin
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Uses of Cyanohydrins
 The nitrile group (CN) can be reduced with LiAlH4 to
yield a primary amine (RCH2NH2)
 Can be hydrolyzed by hot acid to yield a carboxylic acid
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19.7 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 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 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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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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19.8 Nucleophilic Addition of Amines: Imine
and Enamine Formation
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
Formation of 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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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.
These are usually solids and help in characterizing liquid ketones or
aldehydes by melting points
 For example,

hydroxylamine
forms oximes
2,4-dinitrophenylhydrazine
readily forms
2,4dinitrophenylhydrazones

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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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19.9 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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The Wolff–Kishner Reaction: Examples
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19.10 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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Uses of Acetals
 Acetals can be protecting groups for aldehydes & ketones
 Use a diol, to form a cyclic acetal (reaction goes faster)
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19.11 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
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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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19.12 The Cannizaro Reaction
 The adduct of an aldehyde and OH can transfer hydride
ion to another aldehyde C=O resulting in a simultaneous
oxidation and reduction (disproportionation)
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19.13 Conjugate Nucleophilic Addition to Unsaturated Aldehydes and Ketones
 A nucleophile
can add to the
C=C double
bond of an ,unsaturated
aldehyde or
ketone
(conjugate
addition, or 1,4
addition)
 The initial
product is a
resonancestabilized
enolate ion,
which is then
protonated
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Conjugate Addition of Amines
 Primary and secondary amines add to , -unsaturated
aldehydes and ketones to yield -amino aldehydes and
ketones
Reversible so more stable product predominates
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Conjugate Addition of Alkyl Groups:
Organocopper Reactions
 Reaction of an , -unsaturated ketone with a lithium
diorganocopper reagent
 Diorganocopper
(Gilman) reagents
form 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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Mechanism of Alkyl Conjugate
Addition
 Conjugate nucleophilic addition of a diorganocopper
anion, R2Cu, to an enone
 Transfer of an R group and elimination of a neutral
organocopper species, RCu
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19.14 Spectroscopy of Aldehydes
and Ketones
 Infrared
Spectroscopy
 Aldehydes and
ketones show a
strong C=O peak
1660 to 1770
cm1
 aldehydes show
two characteristic
C–H absorptions
in the 2720 to
2820 cm1
range.
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C=O Peak Position in the IR
Spectrum
 The precise position of the peak reveals the
exact nature of the carbonyl group
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NMR Spectra of Aldehydes
 Aldehyde proton signals are at  10 in 1H NMR -
distinctive spin–spin coupling with protons on the
neighboring carbon, J  3 Hz
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13C
NMR of C=O
 C=O signal is at  190 to  215
 No other kinds of carbons absorb in this range
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Mass Spectrometry – McLafferty
Rearrangement
 Aliphatic aldehydes and ketones that have hydrogens
on their gamma () carbon atoms rearrange as shown
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Mass Spectroscopy:
-Cleavage
 Cleavage of the bond between the carbonyl group
and the  carbon
 Yields a neutral radical and an oxygen-containing
cation
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