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27/04/23
Thursday
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28/04/23
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1
Lecture 4
Aldehydes & Ketones
cinnamon
• Industrial sources of
aldehydes and ketones
• Reactions aldehydes &
Ketones
Rose
CHE 311 Organic Chemistry I
Semester1, 2023
Mrs. Monica Sibiya,
University of Goroka
Week 8 (26/04/23)
2
Aims of this lecture
State how methanal, ethanal, propanone (acetone), butanone and
benzaldehyde are produced in industries.
State what nucleophiles are and how they behave towards carbonyl
groups.
State the different nucleophilic attack reactions at the carbonyl
carbon.
 Explain the chemistry of carbonyl group
State the common reactions of aldehydes and ketones.
3
Industrial Sources
Methanal (formaldehyde) is manufactured by the
air-oxidation of methanol which is passed in a
vapour state over a granulated silver (platinum and
copper are occasionally used) catalyst at an
optimum temperature of 560-650 oC
2CH3-OH + O2
CH3-OH
Ag cat
560-650
Ag cat
oC
2HCHO + 2H2O
HCHO + H2
Similarly for ethanal
Similarly, large amount of ethanal are obtained by the
air-oxidation of ethanol
2CH3-CH2-OH + O2
Ag cat
high temp
Ag cat
CH3-CH2-OH
2CH3-CHO + 2H2O
CH3-CHO + H2
It is also obtained by direct dehydrogenation
CH3-CH2-OH
finely divided Cu cat
300 oC
CH3-CHO + H2
The Wacker Process...
Ethanal
Ethene and oxygen under moderate pressure are
passed into an acidified solution containing
palladium(II) chloride and copper (II) chloride at 2060 oC
2Pd + 4HCl + O2
H2C
CH2 + PdCl2 + H2O
2PdCl2 + 2H2O
CH3-CHO + Pd + 2HCl
The copper(II) chloride promotes the second
reaction, enhancing the reconversion of the
palladium back into the palladium(II) chloride
Pd + 2CuCl2
PdCl2 + 2CuCl
The Wacker Process...
Propanone (Acetone)
Propanone is prepared similarly from propene
H2C
CH-CH3 + PdCl2 + H2O
CuCl2
CH3-CO-CH3 + Pd + 2HCl
Butanone (Methyl ethyl ketone)
Butanone is prepared similarly from but-1-ene
H2C
CH-CH2-CH3 + PdCl2 + H2O
CuCl2
CH3-CH2-CO-CH3 + Pd + 2HCl
Benzaldehyde...
Benzaldehyde is manufactured by chlorinating the
side chain of methylbenzene to dichloromethylbenzene and then hydrolysing
CH3
CHCl2
Cl2
CHO
H2O
100 oC
heat
Another technique is to pass methylbenzene
vapour and air over a vanadium(V) oxide
catalyst heated at 350 oC
CHO
CH3
+ O2
V2O5 cat
100 oC
REACTIONS OF ALDEHYDES AND KETONES
9
Reactions of Aldehydes & Ketones
REACTIVITY OF THE C=O GROUP
NUCLEOPHILIC ADDITION
10
What are Nucleophiles?
Nucleophiles are ‘electron rich’ species and have either
non-bonding pairs of electrons or p-bonds.
They can be anions or neutral molecules, e.g.
Nucleophilic anions:
- or OHusually
written
as
HO
HO
- usually written as NC- or CNN
C
Nucleophilic Neutral molecules:
H2O
H2C
H3C
CH2
OH NH3
H2C
CH3-CH2-NH2
CH2CH3
What are nucleophiles?
Nucleophiles can react with species which have
either positive charge or low electron density (i.e. an
electrophile)
This is the basis of many reactions, which begin with
the transfer of electron density from a more
electron-rich atom (in a nucleophile) to an electrondeficient atom (in an electrophile)
Nucleophiles and bases
Nucleophiles are also bases because they react with
protons, H+. Ammonia for example can act both as a
nucleophile or a base:
Nucleophile
NH3 + Br CH2CH3
Br
H3N
CH2CH3
Base
NH3 + HCl
NH4 Cl
Basicity and nucleophilicity are linked but are not
the same thing.
GENERALIZED CHEMISTRY
THE CARBONYL GROUP
The most
characteristic
reaction of
aldehydes and
ketones is
nucleophilic
addition to the
carbon–oxygen
double bond.
.. dO:
C
nucleophilic
at oxygen
electrophiles
add here
H+
or E+
.. :O:
d+
C
+
Nu:
electrophilic
at carbon
nucleophiles
attack here
NUCLEOPHILIC ADDITION TO C=O
MECHANISMS IN ACID AND IN BASE
General scope
O
R
C
Nu
O-
OH
H+
R'
R
R'
Nu
R
R'
Nu
Nucleophilic addition
• Addition is across the C=O double bond
• Rehybridisation of the carbonyl carbon from the sp2 position to the sp3 position
• Electronegative oxygen atom is drawn to the electrons in the pi-bond, resulting in a
tetrahedral alkoxide intermediate
• addition of acid causes the alkoxide to be protonated, resulting in the formation of alcohol
Nucleophilic Addition to Carbonyl
Basic or Neutral Solution
.. _
: O:
..
O:
-:Nu
+
slow
C
C
an
alkoxide
ion
Nu
.. _
: O:
..
:O H
fast
C
Nu
+
H2O
C
or on adding acid
Nu
Good nucleophiles and
strong bases (usually
charged) are used here
BASIC SOLUTION
Nucleophilic Addition to Carbonyl
Acid Catalyzed
+
:O
..
O:
C
+
+
H
fast
C
..
:O
.. +
O H
H
slow
+
C
more reactive to
addition than the unprotonated precursor
H
:Nu
C
Nu
(+)
Acid catalysis speeds the rate of
addition of weak nucleophiles and
weak bases (usually uncharged)
are used here
ACIDIC SOLUTION
pH 5-6
stronger acid
protonates the
nucleophile
HYDRATES
HYDRATES
• Effects of Structure on Equilibrium: Aldehydes and ketones react with water in a
rapid equilibrium:
• Overall, the reaction is classified as an addition.
• The elements of water add to the carbonyl group.
• Hydrogen becomes bonded to the negatively polarized carbonyl oxygen,
hydroxyl to the positively polarized carbon.
20
• Table 17.3 compares the equilibrium constants (Khydr) for hydration of some simple
aldehydes and ketones.
• The position of equilibrium depends on what groups are attached to C=O and how
they affect its steric and electronic environment.
• Both effects contribute, but the electronic effect controls Khydr more than the steric
effect.
21
Comparison with alkenes
As expected there is some correspondence between addition
reactions to carbon-oxygen double bonds and those of the
carbon-carbon double bonds in alkenes.
In the hydration reactions waters adds across the double bond
C
C
+ H
O
H
H
C
C
alcohol
alkene
O
C
carbonyl
OH
+ H
O
H
H
O
C
OH
hydrate
Addition of Water
O
O H
+
H
+
C
H 2O
R
R'
R
aldehyde or ketone
favored
most hydrates revert to an aldehyde
or ketone as soon as they form
O H
R
C
O H
C
R
+
R'
R'
O H
a hydrate
hydrates are unstable
and cannot be isolated
in most cases
O
R'
C
H 2O
BASE CATALYSIS
• The base-catalyzed mechanism is a two-step process in which the first step is
rate-determining.
• The mechanism of hydration of an aldehyde or ketone in basic solution. Hydroxide
ion is a catalyst; it is consumed in the first step, and regenerated in the second.
Step 1: Nucleophilic addition of
hydroxide ion to the carbonyl group
Step 2: Proton transfer from water
to the intermediate formed in the
first step
ACID CATALYSIS
RECALL
H
+
O H
..
H
..
+
:O
:O H
..
:O H
+
Acid catalysis enhances the reactivity
of the carbonyl group - nucleophilic
addition proceeds more easily.
:Nu
weak nucleophiles
can react
Water is a weak nucleophile.
WATER ADDS TO THE CARBONYL GROUP OF
ALDEHYDES AND KETONES TO FORM HYDRATES
H
catalyzed by a
trace of acid
+
..
:O
H
O H
..
..
+ H
:O
H
..
O
..
:O
H
..
H
C
C
O+
H .. H
:O
..
H
..
O
..
H
a hydrate
H
H
+
H
for most compounds the equilibrium
favours the starting materials
and you cannot isolate the hydrate
H
:O
O H
..
MICROREVERSIBILITY:
In a reaction where all steps are
reversible, the steps in the reverse
reaction are the same as those in
the forward reaction, reversed!
Mechanism
1
H2O
H
C
O
H
O
C
O
H
H2O
2
1. Nucleophilic attack on the carbonyl
carbon by a H2O molecule
2. Deprotonation of a hydrogen atom
off the original H2O molecule
3. Protonation of the alkoxide to yield
the hydrate product
H
O
C
O
O
H
H3O
3
HO
H
O
C
O
H
hydrate
ISOTOPE EXCHANGE REVEALS THE PRESENCE
OF THE HYDRATE
O18
O
R
+H2O18
Use of O18 isotope
proves the presence
of hydrate and
reversibility of this
reaction back to
aldehyde or ketone.
R
+ H2O
H+
18
R
excess
O H
R C R
18 O
H
R
an excess of H2O18
shifts the equilibrium
to the right
-H2O
exchange shows the
presence of a symmetric
intermediate
SOME STABLE HYDRATES
these also indicate that hydrates are possible
dCl
d-
Cl
C
d+Cl
d-
Cl
O
H
chloral
120o expected
60o required
O
sp2
cyclopropanone
Cl
OH
C
OH
Cl H
chloral hydrate
OH
sp3 OH
109o expected
60o required
cyclopropanone
hydrate
SOME ADDITIONAL STABLE HYDRATES
O
O
O
H C C
H
glyoxal
O
H
C C OH
H
O
O
Ph C C
phenylglyoxal
H
Ph
OH
Glyoxal hydrate
OH
C C OH
H
Phenylglyoxal hydrate
CYANOHYDRINS
CYANOHYDRINS
• Hydrogen cyanide adds to the carbonyl groups of aldehydes and most ketones to
form compounds called cyanohydrins. (Ketones in which the carbonyl group is
highly hindered do not undergo this reaction.)
• Cyanohydrins form fastest under conditions where cyanide anions are present to
act as the nucleophile.
• Use of potassium cyanide, or any base that can generate cyanide anions from
HCN, increases the reaction rate as compared to the use of HCN alone.
• The addition of hydrogen cyanide itself to a carbonyl group is slow because the
weak acidity of HCN (pKa ≈ 9) provides only a small concentration of the
nucleophilic cyanide anion.
• Cyanohydrins are useful intermediates in organic synthesis because they can be
converted to several other functional groups.
32
Addition of Cyanide
:C N:
Buffered to pH 6-8
.. _
:O :
:O :
_
R
C
R
+
CN
R
C
R
CN
.. _
:O :
R
C
CN
..
:O
R
+
H2O
R
C
H
R
CN
a cyanohydrin
In acid solution there would be little CN-,
and HCN (g) would be a problem (poison).
Cyanohydrin
contains both a
hydroxyl group
and cyano group
bonded to the
same carbon.
Addition of Cyanide Mechanism
The overall reaction:
Step 1: Nucleophilic attack by the negatively charged
carbon of cyanide ion at the carbonyl carbon of the
aldehyde or ketone. Hydrogen cyanide itself is not very
nucleophilic and does not ionize to form cyanide ion to
a significant extent. Thus, a source of cyanide ion such
as NaCN or KCN is used.
Step 2: The alkoxide ion formed in the first step abstracts
a proton from hydrogen cyanide. This step yields the
cyanohydrin product and regenerates cyanide ion.
:C N:
CYANIDE ION BONDS TO HEMOGLOBIN
..
N
CYANIDE
Cyanide bonds
IS A POISON
(irreversibly) to the
C
..
CH3
H3C
site (Fe II) where
oxygen usually bonds.
N
N
Death due to
suffocation lack of oxygen.
Fe
N
N
CH3
H3C
CH2CH2COOH
CH2CH2COOH
HCN is a gas that you can easily breathe into your lungs.
Addition of Cyanide
Example
:C N:
SYNTHESIS OF AN a-HYDROXYACID
O
OH
CH3
NaCN
pH = 8
CH3
CN
Cyanohydrin
1. NaOH/H2O/heat
2. H3O+
OH
Aldehydes also work unless
they are benzaldehydes,
which give a different reaction
(benzoin condensation).
CH3
COOH
ACETALS AND
HEMIACETALS
ACETALS AND HEMIACETALS
• Acetal formation is the result of reaction of aldehydes and ketones that
involves transformation of the initial product of nucleophilic addition to
some other substance under the reaction conditions.
• An example is the reaction of aldehydes with alcohols under conditions of
acid catalysis.
• The expected product of nucleophilic addition of the alcohol to the
carbonyl group is called a hemiacetal.
• The product actually isolated, however, corresponds to reaction of one
mole of the aldehyde with two moles of alcohol to give germinal diethers
known as acetals:
39
ACETALS AND HEMIACETALS
40
ACID CATALYSIS
RECALL
H
+
O H
..
H
..
+
:O
:O H
..
:O H
+
Acid catalysis enhances the reactivity
of the carbonyl group - nucleophilic
addition proceeds more easily.
:Nu
weak nucleophiles
can react
Alcohols are weak nucleophiles.
Addition of Alcohols
TWO MOLES OF ALCOHOL WILL ADD
addition of one mole
O
H+
R C R' + ROH
O H
R C R'
a hemiketal
O R
addition of second mole
O H
R C R'
O R
H+
+
ROH
O R
R C R' + H O
O R
H
a ketal
The equilibria normally favor the aldehyde or ketone starting
material, but we will see how they can be made.
ACETALS AND HEMIACETALS
R
C O
ROH
H aldehyde
R
C
H
OH ROH
OR
hemiacetal
R
C O
R ketone
ROH
R
C
R
OH ROH
OR
R
OR
C
H
OR
acetal
R
OR
C
R
OR
(hemiketal)*
(ketal)*
*older term
*older term
Reaction
Mechanism
+ H 2S O4
R OH
R
..
Like a
hydronium
ion
O+ H
H
R
+
..
H O
:O
..
H
R C R
ACID CATALYZED
FORMATION OF A
HEMIACETAL
..
+
:O H
R C R
H
..
O
..
R C R
H
R
first
addition
H
:O
O+
..
R
..
:
R O
H
..
:O
Normally the starting
material is favored but a second molecule
of alcohol can react
if in excess (next slide)
H
H
R C R
hemiacetal
O
: ..
R
+ R O+
..
H
FORMATION OF THE ACETAL ( from the hemiacetal )
remove
R
+
H O
..
H
H
..
H
:O H
..
R C R
H
O
+
R C R
:O
..
: O..
R
..
O
..
H
H
: ..
O
second
addition
R
R C R
R C R
:O +
:O
SN1
R
R
+
R
hemiacetal
..
..
+ H
:
R O
H
:O R
R
H
R C R
:O
..
R
O:
H
..
O R
+
R C R
:O
..
acetal
R
Resonance
stabilized
carbocation
STABILITY OF ACETALS AND HEMIACETALS
Most hemiacetals are not stable, except for those of sugars.
Acetals are not stable in aqueous acid, but they are stable to
aqueous base.
AQUEOUS
ACID
AQUEOUS
BASE
C
OR H2SO4
OR
H2O
OR NaOH
C
OR H2O
ROH
C O +
ROH
no reaction
ADDITION OF WATER AND ALCOHOLS
WATER
O
H2O
HO
OH
C
hydrate
ALCOHOLS
R-O-H
O
R-O-H
HO
RO
OR
C
H2O
hemiacetal
RO
OR
OR
H+
H2 O
H2O
NaOH
O
+2 ROH
no reaction
acetal
acetals are
stable to base
but not to
aqueous acid
Summary
1. Industrial sources of aldehydes and ketones
• Manufacturing conditions of synthesizing methanol
• Production of ethanol through the Wacker process
• Production of propane (acetone), butanone (methyl ethyl ketone) & benzaldehyde.
2. Reactions of aldehydes and ketones
2.1Nucleophilic addition to the carbon-oxygen double bond
• Reactions in acids and bases and reaction mechanisms
2.2 Addition of water and alcohols: Hydrates, Cyanohydrins, Acetals, and Ketals
• Aldehyde hydrates: GEM-Diols
• Reactions in acids and bases and reaction mechanisms
• Cyanohydrins
• Reaction with hydrogen cyanide (HCN)
• Hemiacetals and acetals
• Reactions in acids and bases and reaction mechanisms
48
49
Tutorial Exercises
1. Refer to tutorial handout
50
Reference
• Solomon T.W. Graham & Fryhle B. Graig, Organic Chemistry 10th
Edition, 2011, John Wiley & Sons Inc, USA; pp 732 – 739
• Carey A. Francis, Organic Chemistry 4th Edition, 2000, The McGrawHill Companies, Inc, USA; pp 662 - 672
51