Transcript Aldehydes and Ketones

Aldehydes and Ketones
Dr. Talat R. Al-Ramadhany
Introduction
Aldehydes are compounds of the general formula RCHO;
Ketones are compounds of the general formula RR´CO. The
groups R and R´ may be aliphatic or aromatic.
O
O
O
C
C
C
Carbonyl group
R
H
Aldehyde
R
R
Ketone
Both aldehydes and ketones contain the carbonyl group,
C=O, and are often called carbonyl compounds.
 An aldehyde is often written as RCHO. Remember that the H
atom is bonded to the carbon atom, not the oxygen.
 Likewise, a ketone is written as RCOR, or if both alkyl groups
are the same, R2CO. Each structure must contain a C––O for
every atom to have an octet.
 The three bonds (carbon, oxygen, and the two other atoms
attached to carbonyl carbon) lie in a plane; the three bond angels
of carbon are very close to 120º.
Nomenclature
Both IUPAC and common names are used for aldehydes
and ketones.
 Naming Aldehydes in the IUPAC System
To name an aldehyde using the IUPAC system:
[1] If the CHO is bonded to a chain of carbons, find the longest
chain containing the CHO group, and change the -e ending of the
parent alkane to the suffix -al.
If the CHO group is bonded to a ring, name the ring and add the
suffix -carbaldehyde.
[2] Number the chain or ring to put the CHO group at C1
Example:
Give the IUPAC name for the compound:
Give the IUPAC name for the compound:
H
H
O
O
H
C
C
O
N
C
3
2
p
n
i
t
r
o
b
e
n
z
e
c
a
r
b
a
l
d
e
h
y
d
e
p
m
e
t
h
y
l
b
e
n
z
e
c
a
r
b
a
l
d
e
h
y
d
e
Common Names for Aldehydes
The common names of aldehydes are derived from the
names of the corresponding carboxylic acids by replacing –ic acid
by –aldehyde.
Greek letters are used to designate the location of substituents
in common names. The carbon adjacent to the CHO group is the `
carbon, and so forth down the chain.
Naming Ketones in the IUPAC System
 To name an acyclic ketone using IUPAC rules:
[1] Find the longest chain containing the carbonyl
group, and change the -e ending of the parent alkane
to the suffix -one.
[2] Number the carbon chain to give the carbonyl carbon
the lower number. Apply all of the other usual rules
of nomenclature.
Common Names for Ketones
Most common names for ketones are formed by
naming both alkyl groups on the carbonyl carbon,
arranging them alphabetically, and adding the word
ketone. Using this method, the common name for
2-butanone becomes ethyl methyl ketone.
O
O
O
H3C C CH3
H3CH2C C CH3
H3CH2CH2C C CH3
Propanone
Acetone
Butanone
Methyl ethyl ketone
2-Pentanone
O
O
C CH3
C CH2CH2CH3
Acetophenone
n-Butyrophenone
O
C
Benzophenone
Physical properties:
Boiling point:
 Aldehydes and ketones are polar compounds due to the
polarity of carbonyl group and hence they have higher boiling
points than non polar compounds of comparable molecular
weight.
 But they have lower boiling points than comparable alcohols or
carboxylic acids due to the intermolecular hydrogen bonding.
Solubility:
The lower aldehydes and ketones soluble in
water, because of hydrogen bonding between carbonyl
group and water, also they soluble in organic solvents.
Preparation of aldehydes & Ketones.
Preparation of aldehydes.
1. Oxidation of primary alcohols:
 Primary alcohols can be oxidized to give aldehydes by using
of K2Cr2O7.
RCH2OH + Cr2O7-1o alcohol
Orange-red
H
R C O + Cr+++
An aldehyde
K2Cr2O7
OH
R C O
A carboxylic acid
Green
2. Oxidation of Methylbenzenes:
In the case of methylbenzenes, oxidation of the side chain
can be interrupted by trapping with acetic anhydride to form
gem-diacetate, which on hydrolysis its return to aldehydes.
ArCH3
CrO3
(AcO)2O
ArCH(OCCH3)2
O
A gem-diacetate
Not oxidized
hydrolysis
ArCHO
O
CHCl2
C H
H2O
CH3
Cl 2
t
a
e
,h
O
ace
t
CrO
ic a
3
nh
yd
rid
e
O
CH(OCCH3)2
C H
H2O
3. Partial reduction of acid chlorides
Strong reducing agents (like LiAlH4) reduce acid chlorides all the
way to primary alcohols. Lithium aluminum tri(t-butoxy)hydride
is a milder reducing agent that reacts faster with acid chlorides than
with aldehydes. Reduction of acid chlorides with lithium aluminum
tri(t-butoxy)hydride gives good yields of aldehydes.
(-78ºC)
4. Partial reduction of esters
Sterically bulky reducing agents, e.g. Diisobutylaluminium
hydride (DIBAH), can selectively reduce esters to aldehydes. The
reaction is carried out at low temperature (-78ºC) in toluene.
H
(H3C)2HCH2C Al CH2CH(CH3)2
Diisobutylaluminium hydride
(mild reducing agent)
O
R C OR
Ester
i. DIBAH , -78oC
ii. H2O
O
R C H
Aldehyde
5. Reduction of Nitriles
Reduction of nitrile with a less powerful reducing reagent,
e.g. DIBAH, produces aldehyde. The reaction is carried out at low
temperatures (-78ºC) in toluene.
O
R C N
Nitrile
i. DIBAH
ii. H2O
R C H
Aldehyde
O
RH2C OH
1o Alcohol
K2Cr2O7, H2SO4
warm
O
i. LiAlH(O-t-But)3
ii. H3O+
R C H
i. CrO , (AcO) O
3
2
ArCH3
ii. hydrolysis
Methylbenzene
O
i. DIBAH
i. DIBAH
ii. H2O
R C N
Nitrile
R C Cl
Acid chloride
+
ii. H3O
R C OR
Ester
Preparation of Ketones
1. Oxidation of Secondary alcohols:
Secondary alcohols are oxidized to ketones by chromic
acid (H2CrO4) in a form selected for the job at hand: aqueous
K2Cr2O7, CrO3 in glacial acetic acid, CrO3 in pyridine, etc. Hot
permanganate also oxidizes alcohols; it is seldom used for the
synthesis of ketones.
R-
RR C OH
H
A 2o alcohol
K2Cr2O7 or CrO3
R C O
Aketone
2. Cleavage of Carbon–Carbon double bond by Ozone:
Oxidative cleavage of an alkene breaks both the σ and π
bonds of the double bond to form two carbonyl groups. Depending
on the number of R groups bonded to the double bond, oxidative
cleavage yields either ketones or aldehydes.
3. Friedel-Crafts acylation.
The Friedel-Crafts reaction involves the use of acid
chlorides rather than alkyl halides. An acyl group (RCO–)
becomes attached to the aromatic ring. Thus forming a ketone; the
process is called acylation.
O
Ar H + R C
Cl
O
AlCl3
or other
Lewis acid
Ar C R +HCl
4. Synthesis of Ketones from Nitriles.
A Grignard or organolithium reagent attacks a nitrile to
give the magnesium salt of an imine. Acidic hydrolysis of the
imine leads to the ketone.
5. Hydration of alkynes.
Alkynes undergo acid-catalyzed addition of water across the
triple bond in the presence of mercuric ion as a catalyst. A mixture of
mercuric sulfate in aqueous sulfuric acid is commonly used as the
reagent.
Reactions of aldehydes and Ketones
Aldehydes and Ketones undergo many reactions to give a
wide variety of useful derivatives. There are two general kinds of
reactions that aldehydes and ketones undergo:
[1] Reaction at the carbonyl carbon (Nucleophilic addition
reactions).
[2] Reaction at the α carbon.
A second general reaction of aldehydes and ketones involves
reaction at the α carbon. A C–H bond on the α carbon to a carbonyl
group is more acidic than many other C–H bonds, because reaction
with base forms a resonance-stabilized enolate anion.
[1] Nucleophilic addition reaction.
Two general mechanisms are usually drawn for nucleophilic
addition, depending on the nucleophile (negatively charged versus
neutral) and the presence or absence of an acid catalyst.
With negatively charged nucleophiles, nucleophilic addition
follows the two-step process first (nucleophilic attack) followed by
protonation.
 Absence of an acid catalyzed nucleophilic addition
Step [1]: The nucleophile attacks the carbonyl group, cleaving the π
bond and moving an electron pair onto oxygen. This forms a sp3
hybridized intermediate with a new C–Nu bond.
Step [2]: protonation of the negatively charged O atom by H2O
forms the addition product.
 Acid-catalyzed nucleophilic addition
The general mechanism for this reaction consists of three
steps (not two), but the same product results because H and Nu- add
across the carbonyl π bond. In this mechanism protonation precedes
nucleophilic attack.
Step [1] Protonation of the carbonyl group
In Step [2], the nucleophile attacks, and then deprotonation forms the
neutral addition product in Step [3].
Steps [2]–[3] Nucleophilic attack and deprotonation
a) Addition of Alcohols (Acetal Formation):
Aldehydes and ketones react with two equivalents of
alcohol to form acetals. In an acetal, the carbonyl carbon from the
aldehyde or ketone is now singly bonded to two OR" (alkoxy)
groups.
b) Nucleophilic Addition of H- (Reduction reaction)
Treatment of an aldehyde or ketone with either Sodium
borohydride (NaBH4) or Lithium hydride (LiAlH4) followed by
protonation forms a 1° or 2° alcohol.
Hydride reduction of aldehydes and ketones occurs via the
two-step mechanism of nucleophilic addition, that is, nucleophilic
attack of H:– followed by protonation.
Examples:
H2 + Ni, Pt
or Pd
O
R
C
LiAlH4 or
R
R
R
NaBH4 then H
C
OH
H
+
O
H
OH
i) LiAlH4
ii) H+
Cyclopentanone
Cyclopentanol
O
OH
i) NaBH4
C
H
C
H
C
3-Phenylacrylaldehyde
(Cinnamaldehyde)
H
+
ii) H
C
H
C
H
C
H
Cinnamyl alcohol
H
c) Reduction to alkane (Deoxygenation of Ketones and Aldehydes):
i) Clemmensen reduction.
ii) Wolff–Kishner reduction.
Clemmensen reduction:
The Clemmensen reduction is most commonly used to
convert acylbenzenes (from Friedel-Crafts acylation) to
alkylbenzenes, but it also works with other ketones or aldehydes that
are not sensitive to acid. The carbonyl compound is heated with an
excess of amalgamated zinc (zinc treated with mercury; Zn (Hg),
and concentrated hydrochloric acid (HCl). The actual reduction
occurs by a complex mechanism on the surface of the zinc.
O
H
C
CH3CH2CH2COCl
CH2CH2CH3 Zn(Hg),
H
C
CH2CH2CH3
conc. HCl
AlCl3
n-Butyrophenone
n-Butylbenzene
The Clemmensen reduction uses zinc and mercury in the presence of strong acid.
O
H3C
(CH2)5
C
Heptanal
H
Zn(Hg)
HCl, H2O
H3C
(CH2)5
CH3
n-Heptane (72%)
H
O
Zn(Hg)
H
HCl, H2O
Cyclohexanone
Cyclohexane (75%)
O
H
C
CH3
Acetophenone
H
C
Zn(Hg), conc. HCl
CH3
1-Ethylbenzene
Wolff–Kishner reduction:
Compounds that cannot survive treatment with hot acid can be
deoxygenated using the Wolff–Kishner reduction. The ketone or
aldehyde is converted to its hydrazone, which is heated with Hydrazine
(NH2NH2), and strong base such as KOH. Ethylene glycol, diethylene
glycol, or another high-boiling solvent is used to facilitate the high
temperature (140-200°C) needed in the second step.
N
O
C
+ H2N
NH2
NH2
C
Hydrazone
+ H2O
H
KOH
Heat
H
C
+ H2O + N N
NNH2
O
H
H
KOH, 175oC
N2H4
Hydrazone
+ N2
HOCH2CH2OCH2CH2OH
(Diethylene glycol)
O
H
C
H
C
C(CH3)3
C(CH3)3
NH2NH2 + OH-
O
H
H
i) NH2NH2
ii) base
Cyclopentanone
Cyclopentane
Summary:
Zn(Hg), conc. HCl
O
C
H
Clemmensen reduction
for compounds sensitive to base
H
Wolff-Kishner reduction
for compounds sensitive to acid
H
NH2NH2, base
C
H
d) Nucleophilic Addition of CN– :
Treatment of an aldehyde or ketone with NaCN and a strong
acid such as HCl adds the elements of HCN across the
carbon–oxygen π bond, forming a cyanohydrin.
H
C O
NaCN
NaHSO3
Benzaldehyde
H
C CN
OH
Mandelonitrile
O
H3C
C
CH3
CH3
CH3 + NaCN
Acetone
H2SO4
H3C
C
CN
H2O, H2SO4
H3C
COOH
C
OH
OH
Acetone cyanohydrin
- H2O
CH3
H2C
C
COOH
Methacrylic acid
e) Addition of Bisulfate.
Sodium bisulfate adds to most aldehydes and to many ketones
(especially methyl ketones and cycloketones) to form bisulfate addition
products:
O
C
+ Na+ HSO3-
C
SO3- Na+
OH
A bisulfate
addition product
O-
O
OH
+
C
C
:SO3HNucleophilic
reagent
SO3-
H
C
SO3-
Examples:
OH
O
C H + Na+ HSO3-
C
SO3- Na+
H
O
H3CH2C
C
n-Butanone
OH
+
CH3 + Na
HSO3-
H2O
H3CH2C
C
CH3
SO3- Na+
O
H3C
H
C
CH3
C
H
C
+
CH3 + Na HSO3
-
H2O
No reaction ?
CH3
Isopropyl ketone
2,4-Dimethyl-3-pentanone
Ketones containing bulky groups usually fail to react
with bisulfate, because of steric effect.
f) Addition of organometallic reagents (R–)
The addition of Grignard reagents to aldehydes and ketones
yields alcohols. The organic group, transferred with a pair of electrons
from magnesium to carbonyl carbon, is a powerful nucleophile.

O
C


+ R: MgX
C OMgX
R
H2O
C OH + Mg(OH)X
R
H+
Mg++ + X- + H2O
g) Addition of derivatives of Ammonia (Formation of imine).
 Treatment of an aldehyde or ketone with a 1° amine affords an
imine (also called a Schiff base).
 Nucleophilic attack of the 1° amine on the carbonyl group forms an
unstable carbinolamine, which loses water to form an imine. The
overall reaction results in replacement of C=O by C=NR.
Oxidation reaction

Aldehydes are readily oxidized to yield carboxylic acids; but
ketones are generally inert toward oxidation.

The difference is a consequence of structure: aldehydes have a
–CHO proton that can be abstracted during oxidation, but ketones
do not.
Hydrogen here
O
C
R
H
An aldehyde
[O]
R
O
O
C
C
OH
Carboxylic acid
R
R
Aketone
No hydrogen
here

Many oxidizing agents, including KMnO4 and hot HNO3,
convert aldehydes into carboxylic acid.
But CrO
in aqueous acid is a more common choice in the
laboratory. The oxidation occurs rapidly at room temperature and
results in good yields.
3
hot HNO3
RCHO or ArCHO
KMnO4
K2Cr2O7
RCOOH or ArCOOH
Tollen's reagent
In the laboratory, oxidation of an aldehyde can be carried out
using a solution of silver oxide (Ag2O) in aqueous ammonia, the
so-called Tollen's reagent. Oxidation of aldehyde is accompanied by
reduction of silver ion to free silver (in the form of a mirror under the
proper conditions).
O
C
H3C
H
+ Ag(NH3)2+ + 3OHColorless
solution
2Ag + CH3COO- + 4NH3 + 2H2O
Silver
mirror
O
O
C
H
Ag2O
C
OH
NH4OH, H2O,
Ethanol
Benzaldehyde
Benzoic acid
+ 2Ag
Methyl ketones:
Oxidation of ketones required breaking of C–C bond next to
the carbonyl group and takes place only under vigorous conditions,
except for methyl ketones which oxidized smoothly by mean of
hypohalite (NaOX) to form Haloform (Haloform reaction).
Reactions of aldehydes and Ketones
Aldehydes and Ketones undergo many reactions to give a
wide variety of useful derivatives. There are two general kinds of
reactions that aldehydes and ketones undergo:
[1] Reaction at the carbonyl carbon (Nucleophilic addition reactions).
[2] Reaction at the α carbon.
A second general reaction of aldehydes and ketones involves
reaction at the α carbon. A C–H bond on the α carbon to a carbonyl
group is more acidic than many other C–H bonds, because reaction
with base forms a resonance-stabilized enolate anion.
[2] Reaction involving acidic α-hydrogen
The carbonyl strengthens the acidity of the hydrogen atoms
attached to the α-carbon and, by doing this, gives rise to a
whole set of chemical reactions.
Ionization of an α-hydrogen, yields a carbanion (I) that is a
resonance hybrid of two structures: Keto form and Enol form.
H
O
C
C
O
+ :B
C
C
+ B:H
(I)
O
H O
C C
C C
keto form
Enol form
O
equivalent to
C
C
(I)
a) Halogenation of ketones:
When
a ketone is treated with a halogen and base, an
α-halogenation reaction occurs.
b) Aldol condensation
 Under the influence of
dilute base or dilute acid , two molecules
of an aldehyde or a ketone, which contained α-hydrogen , may
combine to form a β-Hydroxy aldehyde or β-Hydroxy ketone.
This reaction is called the Aldol condensation .
A
l
d
e
h
y
d
e
a
l
c
o
h
o
l
Mechanism:
If
aldehyde or ketone does not contain an α-hydrogen, a
simple Aldol condensation cannot take place.
For example:
ArCHO
HCHO
(CH3)3CCHO
ArCOAr
ArCOCR3
No
-hydrogen
atoms
dilute OH-
No reaction
Cannizzaro reaction.
In the presence of concentrated alkali, aldehydes containing
no α-hydrogen undergo self-oxidation and reduction to yield a
mixture of an alcohol and a salt of a carboxylic acid. This reaction
is known as the Cannizzaro reaction.
H
2
C O
An aldehyde with
no hydrogen
strong base
COOAcid
salt
+
CH2OH
Alcohol
Examples:
H
50% NaOH
2 H C O
Formaldehyde
2 O2N
CHO
room temp.
35%NaOH
p-Nitrobenzaldehyde
O2N
H COO+
Formate ion
CH2OH
50%KOH
+
2
m-Chlorobenzaldehyde
COO- Na+
Sodiump-nitrobenzoate
COO-
Cl
Methanol
CH2OH + O2N
p-Nitrophenyl alcohol
CHO
CH3OH
Cl
m-Chlorobenzoate
ion
Cl
m-Chlorobenzyl
alcohol
Crossed Cannizzaro reaction
If
two different aldehydes with no α-hydrogen undergo
Cannizzaro reaction yield a mixture of products. This reaction is
called crossed Cannizzaro reaction.
A
rC
H
O+H
C
O
H
conc.N
aO
H
CHO
+
A
rC
H
O
H
+
H
C
O
O
N
a
2
CH2OH
+ HCOH
OCH3
Anisaldehyde
m-Methoxybenzaldehyde
conc. NaOH
+ HCOO- Na+
OCH3
m-Methoxybenzyl
alcohol