Aldehydes and Ketones Structures and Reactions

C 2004 Barry Linkletter, UPEI
ALDEHYDES AND KETONES
The Carbonyl Group

The carbonyl group consists of
one bond formed by the overlap of sp2 hybrid
orbitals, and
one bond formed by the overlap of parallel 2p
orbitals
Structure of Aldehydes
The functional group of an aldehyde is a
carbonyl group bonded to a H atom
in methanal, it is bonded to two H atoms
in all other aldehydes it is bonded to one H and
one carbon atom
H
H
C
H
M e t ha na l
( fo rm a lde hy de )
H3 C
E tha na l
( a c e t a lde hyde )
Structure of Ketones
The functional group of a ketone is a
carbonyl group bonded to two carbon atoms
O
CH3 -C-CH3
Propanone
(Acetone)
Cyclohexanone
Nomenclature-Aldehydes
IUPAC names: select as the parent alkane the
longest chain of carbon atoms that contains the
carbonyl group
because the carbonyl group of the aldehyde must be on

carbon 1, there is no need to give it a number
For unsaturated aldehydes, show the presence of

the C=C by changing the infix -an- to -en the location of the suffix determines the numbering
pattern
Nomenclature-Aldehydes
O
CH3CH
O
CH3CH2CH
CH3
CH3CHCH2CH2CHCH
CH2CH3
ethanal
propanal
2-ethyl-5-methylhexanal
Nomenclature-Aldehdyes
For cyclic molecules in which the -CHO
group is attached to the ring, the name is
derived by adding the suffix -carbaldehyde
to the name of the ring
O
C
H cyclohexanecarbaldehyde C
2-cyclopentenecarbaldehyde
Nomenclature-Ketones
IUPAC names:
select as the parent alkane the longest chain
that contains the carbonyl group,
indicate its presence by changing the suffix -e
to -one, and
number to give C=O the smaller number
O
CH3CH2CCH2CH2CH2
3-hexanone
O
CH3CH
CHCH2CCH3
4-hexen-2-one
CH3CH2CCH2CCH3
2,4-hexanedione
Nomenclature-Ketones
The IUPAC system retains the names
acetone, acetophenone, and benzophenone
O
C H3 C C H3
A c e to ne
C C H3
C-
A c e to phe no ne
B e nzo phe no ne
Physical Properties
Oxygen is more electronegative than carbon (3.5
vs 2.5) and, therefore, a C=O group is polar
aldehydes and ketones are polar compounds and interact
in the pure state by dipole-dipole interaction
they have higher boiling points and are more soluble in
water than nonpolar compounds of comparable molecular
weight
+ C
O
Preparation of Aldehydes
Primary Alcohols are oxidized to aldehydes.
CH2OH
PCC
CH2Cl2
CHO
Alkenes with a vinylic hydrogen undergo oxidative cleavage
when treated with ozone to yield aldehydes.
On cyclic alkenes a dicarbonyl compound is formed
1. O3
2. Zn, CH3COOH
CH3CCH2CH2CH2CH2CH
O
CH3(CH2)10COCH3
1. DI BAH, toluene, -78 C

2. H3O+
O
CH3(CH2)10CH
H
DIBAH =
(CH3)2CHCH2 Al
CH2CH(CH3)2
Preparation of Ketones
Secondary alcohols are oxidized to give ketones.
(CH3)3C
OH
PCC
CH2Cl2
(CH3)3C
Ozonolysis of alkenes yields ketones if one of the
unsaturated carbon atoms is disubstituted.
CH2
CH3
1. O3
2. Zn, CH3COOH
O
CH3
+ CH2O
Aryl ketones are prepared by Friedel-Crafts
acylation of an aromatic ring with an acid chloride
in the presence of AlCl3 catalyst.
O
O
CH3CCl
AlCl3
HEAT
CH3
Methyl ketones are prepared by hydration of
terminal alkynes in the presence of Hg2+ catalyst.
CH3(CH2)3C CH
H3O+
HgSO4
O
CH3(CH2)3C CH3
REACTIONS OF ALDEHYDES
AND KETONES
Reaction Themes
One of the most common reaction themes
of a carbonyl group is addition of a
nucleophile to form a tetrahedral carbonyl
addition compound
O
R
Nu
C
R
Nu
C
R
R
Tetrahedral carbonyl
addition compound
Reaction Themes
A second common theme is reaction with a
proton or Lewis acid to form a resonancestabilized cation
R
R
+ H-B
fast
R
C
R
+
O H
+ B
protonation in this manner increases the

electron deficiency of the carbonyl carbon and
makes it more reactive toward nucleophiles
Nucleophilic Addition Reactions of Aldehydes

and Ketones
Nu- approaches the C=O and adds to C
A tetrahedral alkoxide ion intermediate is
produced
Nucleophiles
Nucleophiles can be negatively charged ( : Nu) or neutral ( :
Nu) at the reaction site
The overall charge on the nucleophilic species is not
considered
Reactivity of Aromatic Aldehydes

Less reactive in nucleophilic addition reactions
than aliphatic aldehydes
Electron-donating resonance effect of aromatic
ring makes C=O less reactive electrophilic than
the carbonyl group of an aliphatic aldehyde
Relative Reactivity
O
Electron-donating resonance effect of

aromatic ring makes the carbonyl less
electrophilic than the carbonyl group in
an aliphatic aldehyde.
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
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 C=O makes
it more electrophilic
Nucleophlic Addition of HCN

Aldehydes and ketones react with HCN to yield
cyanohydrins,
RCH(OH)C N
O
C
HO
H
HCN
CN
C

Addition of CN- to a ketone or aldehyde occurs by a typical
nucleophilic addition pathway.
Tetrahedral intermediate that is protonated by HCN to give
a cyanohydrin regenerates the CN-
O
C
O
H
C N
HO
CN
C
HCN
CN
C
C N

O
C
OH
OH
H
HCN
CHCN
1. LiAlH4, THF
2. H2O
CHCH2NH2
OH
+
H3O , heat
CHCOOH
Addition of Alcohols
A ketone or aldehyde reacts reversibly with two
equivalents of an alcohol in the presence of an acid
catalyst to yield an acetal, R2C(OR)2.
O
R
OR
2ROH
R
R
R
OR
H2O
Acidic conditions cause protonation of the
carbonyl group.
Reactivity is increased.
O
C
H A
O
C
Protonated carbonyl group

(strongly electrophilic and highly
reactive toward nucleophiles)
H Cl
ROH
O
C
H
O
R
OH2
OH2
C
H Cl
OR
ROH
O
C
H3O+
OR
hemiacetal
R
O
O
C
R
OH2
R
O
acetal
Addition of one molecule of alcohol to the
C=O group of an aldehyde or ketone gives a
hemiacetal
Hemiacetal: a molecule containing an -OH
and an -OR or -OAr bonded to the same
carbon
O
CH3 CCH3 + OCH2 CH3
OH
CH3 COCH2 CH3
CH3
A hemiacetal
Hemiacetals are only minor components of
an equilibrium mixture, except where a
five- or six-membered ring can form
(the trans isomer is shown here)
O
CH3 CHCH2 CH2 CH
OH
4-Hydroxypentanal
H3 C
OH
A cyclic hemiacetal
(major form present
at equilibrium)
Formation of a hemiacetal is acid-catalyzed
Step 1: proton transfer from the acid, HA, to
the carbonyl oxygen
CH3 -C-CH3 + A -
CH3 -C-CH3 + H-A
+
O-H
Step 2: attack of ROH on the carbonyl carbon
followed by proton transfer to A- to
regenerate the acid catalyst
+
O-H
CH3 -C-CH3 + H-O-R
O-H
O-H
CH3 -C-CH3 + H-A

O-R
CH3 -C-CH3
+
O
- H R
A
Hemiacetals react with alcohols to form
acetals
Acetal: a molecule containing two -OR or
-OAr groups bonded to the same carbon
OH
CH3 COCH2 CH3 + CH3 CH2 OH
CH3
A hemiacetal
OCH2 CH3
CH3 COCH2 CH3
CH3
A diethyl acetal
H2 O
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 +.
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
OXIDATION OF ORGANIC
COMPOUNDS
Oxidation of Aldehydes and

Ketones
Oxidizing agents
KMnO4/HNO3
CrO3
Ag2O/NH3
O
R
[O]
H
O
R
[O]
R
OH
no reaction

Ketones
One drawback is that it takes place under acidic
conditions.
Sensitive molecules undergo side reactions.
O
CH3(CH2)4CH
CrO3, H3O
acetone
O
CH3(CH2)4COH

Ketones
Tollens reagent, Ag2O/NH3, acid without harming
carbon-carbon double bonds or other functional
groups.
O
H
Ag2O
NH4OH, H2O,
EtOH
O
OH

Ketones
Occur through intermediate 1,1-diols, or hydrates. Formed
by reversible nucleophilic addition of water to the carbonyl
group.
Reacts like typical primary or secondary alcohol.
OH
O
R
C
H
OH
CrO3
H3O+
OH

Ketones
Ketones are inert to most oxidizing agents.
They do undergo slow cleavage in hot alkaline
KMnO4.
1. KMnO4, H2O,
NaOH
+
2. H3O
COOH
COOH
REDUCTION OF CARBONYL
COMPOUNDS
Reduction
Aldehydes can be reduced to 1 alcohols
and ketones to 2 alcohols. In addition, the
C=O group can be reduced to a -CH2- group
Aldehydes
O
RCH
Can be
Reduced to
RCH2 OH
RCH3
Ketones
O
RCR'
Can be
Reduced to
OH
RCHR'
RCH2 R'
Catalytic Reduction
Catalytic reductions are generally carried
out from 25 to 100C and from 1 to 5 atm
H2
O
OH
+ H2
Cyclohexanone
Pt
25oC, 2 atm
Cyclohexanol
Catalytic Reduction
A carbon-carbon double bond may also be
reduced under these conditions
O
H
CH
2H2
C C
Ni
H3 C
H
trans-2-Butenal
(Crotonaldehyde)
CH3 CH2 CH2 CH2 OH

1-Butanol
by careful choice of experimental conditions, it

is often possible to selectively reduce a carboncarbon double in the presence of an aldehyde or
ketone
Metal Hydride Reduction

The most common laboratory reagents for
the reduction of aldehydes and ketones are
NaBH4 and LiAlH4
both reagents are sources of hydride ion, H:-, a
very powerful nucleophile
H
H
Sodium
borohydride
Li+ H-Al-H
H
Lithium aluminum
hydride (LAH)
Na H-B-H
Hydride ion
NaBH4 Reduction
Reductions with NaBH4 are most commonly
carried out in aqueous methanol, in pure
methanol, or in ethanol
One mol of NaBH4 reduces four mol of
aldehyde or ketone
O
4RCH + NaBH4
methanol
+ H2 O
(RCH2 O)4 B Na
-
A tetraalkyl borate
4RCH2 OH + borate
salts
NaBH4 Reduction
The key step in metal hydride reduction is
transfer of a hydride ion to the C=O group
to form a tetrahedral carbonyl addition
compound
H
+
Na H-B-H + R-C-R'
O BH3 Na
R-C-R'
H
from the hydride

reducing agent
H2 O
OH
R-C-R'
H
from
water
LiAlH4 Reduction
Unlike NaBH4, LiAlH4 reacts violently with
water, methanol, and other protic solvents.
Reductions using it are carried out in
diethyl ether or tetrahydrofuran (THF)
O
ether
4RCR + LiAlH4
-
(R 2 CHO)4 Al Li
A tetraalky aluminate
H2 O
OH
4RCHR + aluminum salts
Metal Hydride Reduction

Metal hydride reducing agents do not
normally reduce carbon-carbon double
bonds, and selective reduction of C=O or
C=C is often possible
O
RCH=CHCR'
1. NaBH4
2. H 2 O
O
RCH=CHCR' + H2
Rh
OH
RCH=CHCHR'
O
RCH2 CH2 CR'
Clemmensen Reduction
Refluxing an aldehyde or ketone with
amalgamated zinc in concentrated HCl
converts the carbonyl group to a methylene
group
OH
O
C(CH 2 ) 5 CH3
Z n(Hg), HCl
OH
CH2 (CH2 ) 5 CH3
Wolff-Kishner Reduction
In the original procedure, the aldehyde or
ketone and hydrazine are refluxed with
KOH in a high-boiling solvent. The same
reaction can be brought about using
hydrazine and potassium tert-butoxide in
DMSO
O
CCH3 + H2 NNH2
KOH
diethylene glycol
Hydrazine
(reflux)
CH2 CH3 + N2
+ H2 O
Wolff-Kishner Reduction
O
R
N
R
NH2
OH
N
H2O
R
N H
N
R
N H
R
H2O
H
R
R
H2O
H
H2O N N R
R
N
H
R
N H
C
R H
OH
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
Conjugate Addition of Amines

Primary and secondary amines add to , unsaturated aldehydes and ketones to yield amino aldehydes and ketones
Wittig Reaction
The Wittig reaction is a very versatile
synthetic method for the synthesis of
alkenes from aldehydes and ketones.
+ P h 3 P -C H 2
A pho s pho nium
y lide
C H2
M e t hy le ne c y c lo he x a ne
+
+ P h P -O
3
T riphe ny lpho s phine o x ide
Wittig Reaction
CH3
1. CH3MgBr
2. POCl3
CH2
_
(C6H5)3P+ CH2THF
CH2
Wittig Reaction
CH3CH2C=O
CH2CH3
+_
CHCH3
(C6H5)3P
THF
CH3CH2C=CHCH3
CH2CH3
Wittig Reaction
Examples:
O
+ CH3 CCH3 + Ph3 P-CH(CH 2 ) 3 CH3
CH3
+ CH3 C=CH(CH2 ) 3 CH3 + Ph3 P-O

2-Methyl-2-heptene
Addn of N Nucleophiles
Ammonia, 1 aliphatic amines, and 1
aromatic amines react with the C=O group
of aldehydes and ketones to give imines
(Schiff bases)
O
CH3 CH + H2 N
CH3 CH=N
Aniline
Ethanal
+ H2 O
An imine
(A Schiff base)
+
O
Cyclopentanone
+ H2 NCH3
Methylamine
NCH3
An imine
(a Schiff base)
+ H2 O
Formation of an imine occurs in two steps
Step 1: addition of the nitrogen nucleophile to

the carbonyl carbon followed by proton
transfer
H
H
O
O
+ H2 N-R
C N-R
C N-R
H
H
A tetrahedral carbonyl
addition compound
Step 2: protonation of the -OH followed by loss
of H2O and proton transfer to solvent
H
O
An imine
+ H2O
A value of imines is that the carbonnitrogen double bond can be reduced to a
carbon-nitrogen single bond
Cyclohexanone
H2 N
H+
-H2 O
Cyclohexylamine
N
(An imine)
H2 /Ni
H
N
Dicyclohexylamine
Secondary amines react with the C=O
group of aldehydes and ketones to form
enamines
+
O + H-N
Piperidine
(a secondary amine)
N
An enamine
+ H2 O
The carbonyl group of aldehydes and
ketones reacts with hydrazine and its
derivatives in a manner similar to its
reactions with 1 amines
O + H2 NNH2
Hydrazine
NNH2
A hydrazone
Hydrazine
H2 N-OHderivatives include
H2 N-NH
Phenylhydrazine
Hydroxylamine
+ H2 O
Acidity of -Hydrogens
Hydrogens alpha to a
carbonyl group are more
acidic than hydrogens
of alkanes, alkenes, and
alkynes but less acidic
than the hydroxyl
hydrogen of alcohols
Type of Bond
pKa
CH3 CH2 O-H 16
O
CH3 CCH2 -H
20
CH3 C C-H
25
44
51
CH2 =CH-H
CH3 CH2 -H
Acidity of -Hydrogens
-Hydrogens are more acidic because of
1. the electron-withdrawing inductive effect of
the adjacent carbonyl group weakens the C-H
bond and
2. delocalization of the negative charge stabilizes
the resulting enolate anion
O
CH3 -C-CH 2 -H +
AO
CH3 -C-CH 2
OCH3 -C=CH2
Resonance-stabilized enolate anion
+ H-A
Keto-Enol Tautomerism
Protonation of the enolate anion on oxygen
gives the enol form; protonation on carbon
gives the keto form
O-
CH3 -C-CH2
CH3 -C=CH2
Enolate anion
H-A
A - + CH3 -C-CH3
Keto form
H-A
OH
CH3 -C=CH2 + A
Enol form
Acid-catalyzed equilibration of keto and
enol tautomers occurs in two steps
Step 1: proton transfer to the carbonyl oxygen
+
H
O
O
fast
CH3 -C-CH3 + H-A
CH3 -C-CH3 + A keto form
Step 2: proton transfer to A- to give the enol
+
CH3 -C-CH2 -H + A
slow
OH
CH3 -C=CH2 + H-A
Enol form
-Halogenation
-Halogenation: aldehydes and ketones
with at least one -hydrogen react at an
-carbon with Br2 and Cl2
O
CCH3 + Br 2
Acetophenone
CH3 CO2 H
O
CCH2 Br + HBr
reaction is catalyzed by both acid and base
-Halogenation
Acid-catalyzed -halogenation
Step 1: acid-catalyzed enolization
OH
H-O
slow
R'-C-C-R
C
R
C
R'
C
R'
C
R
Br-Br
fast
Step 2: Nucleophilic attack of the enol on
R
halogen
Br
H-O
O
C
R'
C R
R
+ H-Br
-Halogenation
Base-promoted -halogenation
Step 1: formation of an enolate anion

O
R
OH
slow
+ H2 O
C C
R'-C-C-R +
OH
R'
R
R
Resonance-stabilized
enolate anion
-Halogenation
Base-promoted -halogenation (contd.)
Step 2: nucleophilic attack of the enolate anion
on halogen
C
R'
O Br
Br-Br
fast
R'-C-C-R + Br
R
Haloform Reaction
In the presence of base, a methyl ketone
reacts with three equivalents of halogen to
form a 1,1,1-trihaloketone, which then
reacts with an additional mol of hydroxide
ion to form a carboxylic salt and a
trihalomethane
O
RCCH3
3Br 2
3NaOH
O
RCCBr 3
O
NaOH
RCO Na
+ CHBr3
Tribromomethane
(Bromoform)
Haloform Reaction
The final stage is divided into two steps
Step 1: addition of OH- to the carbonyl group to
form a tetrahedral carbonyl addition
intermediate, followed by its collapse
O
RC-CBr 3 + OH
O
RC-CBr 3
OH
O
RC
OH
CBr 3
Haloform Reaction
Step 2: proton transfer from the carbonyl group
to the haloform anion
O
RC-O-H +
O
CBr 3
RC-O
+ H-CBr 3
Bromoform
Test for aldehydes and ketones

Tollens (works for aliphatic aldehydes,
aromatic aldehyde reacts slowly, ketones
NO reactions)
Fehlings (works only for aliphatic
aldehydes, aromatic aldehydes and ketones
NO reactions)
Tollens and Fehlings tests

Tollen's test
H
Ag2O
OH
Ag (silver mirror ppt)
O
propanoic acid
propanal
ketone
no reaction
Fehling's test
H3C
O
ethanal
ketone
2CuO
H3C
OH
O
no reaction
Cu2O (red ppt)

Aldehydes and Ketones Structures and Reactions

Transféré par

Informations du document

Description originale:

Titre original

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

Aldehydes and Ketones Structures and Reactions

Transféré par

Droits d'auteur :

Formats disponibles

C 2004 Barry Linkletter, UPEI