An Oxidation Reaction: Adipic Acid from Cyclohexanone
Introduction
Oxidation reactions involve the addition of oxygen or the removal of
hydrogen. First, we shall learn to identify structures that can undergo oxidation.
Then, we shall learn the reagents that can oxidize the structures. Oxidation
reactions require an “activated” carbon atom such as that shown in Figure 1 where
the carbon is bonded to an oxygen atom and to at least one hydrogen atom. The
carbon atom shown in the red square is bonded to oxygen and to a hydrogen atom.
The hydrogen atoms are shown in blue. Oxidation involves the removal of the two
blue hydrogen atoms. Figure 1 shows the oxidation of an alcohol and the formation
of the carbonyl group. A mild oxidizing agent can accomplish this reaction.
O H
minus 2H
O
C
C
H
Figure 1. Oxidation of an alcohol.
Aldehydes may be oxidized to carboxylic acids because the carbon atom of
an aldehyde is bonded to oxygen and to hydrogen. Figure 2 shows the oxidation of
an aldehyde to a carboxylic acid. Again, the oxidation involves a carbon atom that
is bonded to oxygen and to hydrogen, but a stronger oxidizing agent is required for
this reaction than the one shown in Figure 1.
O
R C
minus H
O
R C
H
plus OH
OH
Figure 2. Oxidation of an aldehyde.
Alcohols are classified as primary (Io), secondary (IIo) or tertiary (IIIo),
depending on how many hydrogen atoms share the carbon atom bearing a hydroxyl
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group. Figure 3 shows examples of methyl, Io, IIo and IIIo alcohols, with the carbon
atom bearing the hydroxyl group shown in a red square.
OH
OH
H C H
H
methanol
CH3 C H
H
ethanol
methyl
Io
OH
OH
CH3 C CH3
H
2-propanol
CH3 C CH3
CH3
o
II
2-methyl-2-propanol
IIIo
Figure 3. Alcohols.
Look at the structures of the four alcohols in Figure 3. Which of these
alcohols can be oxididized under normal lab conditions? Those with blue hydrogen
atoms can be oxidized. The blue H atoms are bonded to carbon atoms that are also
bonded to oxygen. What do we mean by normal lab conditions? We exclude
combustion (oxidation) reactions that convert hydrocarbons and alcohols into
carbon dioxide and water. We use common laboratory oxidizing reagents.
We are now ready to consider reagents that will oxidize “oxidizable” carbon
atoms. Figure 4 shows the four kinds of alcohols and the various oxidized products
that can be obtained by oxidizing them with specific oxidizing reagents.
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O
OH
PCC
CrO3/H+
H C H
H C H
O
O
HO C OH
C
(pyridinium
chlorochromate)
H
O
carbon
dioxide
methanal
methanol
OH
CH3CH2 C H
O
PCC
CH3CH2 C H
CrO3/H+
O
CH3CH2 C OH
H
OH
CH3CH2 C CH3
H
propanoic acid
propanal
1-propanol
O
PCC
or CrO3/H+
CH3CH2 C CH3
2-butanone
2-butanol
OH
CH3CH2 C CH3
CH3
PCC
or CrO3/H+
No reaction
2-methyl-2-butanol
Figure 4. Oxidation reactions.
Summary of Figure 4
Pyridinium chlorochromate (PCC) is a mild oxidizing agent and chromic
acid (CrO3/H+) is a strong oxidizing agent. Mild oxidizing agents can oxidize
oxidizable carbon atoms in alcohols to aldehydes. Strong oxidizing agents oxidize
any oxidizable alcohol carbon until it is no longer oxidizable. PCC oxidizes only
methanol and primary alcohols to aldehydes. Chromic acid oxidizes any compound
that contains blue hydrogens bonded to a carbon bonded to oxygen and continues
to oxidize (remove blue H’s) until no blue H’s are left bonded to carbon.
Table 1 shows mild and strong oxidizing agents.
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Table 1. Oxidizing agents.
Mild Oxidizing Agents
Strong Oxidizing Agents
Name
Formula
Name
Formula
Pyridinium
chlorochomate
PCC
Chromic acid or
Potassium
dichromate
CrO3/H+
Potassium
permanganate
KMnO4/OH-
K2Cr2O7
The reagents in Table 1 all contain a transition metal, either chromium(VI)
or manganese(VII), that can be reduced. Pyridinium chlorochromate, PCC, is a
modified form of chromic acid. PCC can be used in an organic solvent. The
combination of an organic solvent and the presence of pyridine decreases the
oxidizing power of Cr(VI), making PCC ideal for converting suitable alcohols to
aldehydes or ketones. Chromic acid and potassium permanganate are both used in
an aqueous medium. Because KMnO4 is used in a basic medium, any organic acid
product is produced as a salt that must be acidified to obtain the organic acid.
Oxidation of Arene Side Chains
The strong oxidizing agents listed in Table 1 are capable of oxidizing side
chains in arenes to the corresponding carboxylic acid. Figure 5 shows two such
reactions.
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O
(1) KMnO4
OH
(2) H+
O
O
HCrO4
OH
Figure 6. Oxidation of arene side chains.
Nitric Acid, HNO3, as an Oxidizing Agent
This experiment involves the oxidation of a cyclic ketone to a dicarboxylic
acid, as shown in Equation 1.
O
O
strong
OH
HO
oxidation
cyclohexanone
(six carbon atoms)
O
adipic acid
(six carbon atoms)
Equation 1. Oxidation of Cyclohexanone to Adipic Acid.
The reaction requires a stronger oxidizing agent than is shown in Table 1,
because the carbonyl carbon is not oxidizable by common oxidizing agents. The
carbonyl carbon is part of a ketone and does not have a hydrogen bonded to it.
Nitric acid is a special oxidizing agent that can oxidize “non-oxidizable” carbon
atoms of cyclic ketones. The reaction produces a diacid with the same number of
carbon atoms found in the starting cyclic ketone. The scheme in Figure 6 is not a
mechanism but a nice way to understand this reaction and other oxidation reactions
as well. The methodology was published by Louis and Mary Fieser in their books.
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O

H
H
O
O
OH
[O]
H
Step 1
[O]
O
minus H2O
OH
Step 3
Step 2
-hydroxyketone
ketone
O
OH
gem-diol
diketone
O
O
O
[O]
HO
Step 4
diketone
OH
O
adipic acid
(1,6-hexanedioic acid)
Figure 6. Oxidation Methodology.
We determine that the bond that is most easily oxidized is the C-H bond
alpha to the carbonyl group in cyclohexanone. When this bond is cleaved, Step 1,
we replace the H atom with an –OH group. The generalized methodology is to
place –OH groups on open valences where bonds break. The -H atom is the one
nearest the O atom in cyclohexanone. Replacing it with an –OH group gives anhydroxyketone, which is a secondary alcohol with an oxidizable carbon atom.
Oxidzing the secondary alcohol gives a gem-diol, which immediately loses water
to form a 1,2-diketone. The bond lying between the two carbonyl groups is the
weakest bond and is susceptible to further oxidation. Cleaving this bond and
adding two –OH groups to the open valences gives the diacid adipic acid. This is a
quantitative reaction that converts a liquid (cyclohexanone) into a solid (adipic
acid).
Procedure
1. On a balance, tare a small test tube that has been placed in an empty 50 to 100mL beaker for stabilization.
2. Carefully add cyclohexanone, drop wise, to the small test tube until the balance
shows a mass of 0.15 g.
3. Record the exact mass, which is at least 0.150 g, directly in your notebook as
mass of cyclohexanone.
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4. Set up a sand bath (metal heating mantel filled with sand, connected to a
rheostat) under a fume hood.
5. Place 1-mL concentrated nitric acid into a centrifuge tube.
It has been found over several years of conducting this experiment that a
six-in centrifuge tube or 6-in test tube works better than a small test tube or Craig
tube.
6. Working under the hood, add one drop of cyclohexanone to the centrifuge tube
that contains the nitric acid.
Always point the opening of the centrifuge tube away from
yourself and others. Point it toward the back of the hood. If you spill
acid on yourself, wash the affected are quickly and thoroughly with
water.
7. Warm the centrifuge tube on the sand bath until a brown gas is observed.
Nitric acid is reduced as it oxidizes cyclohexanone. The reduction products
include a brown gas, which is nitrogen dioxide, NO2. When you observe the
brown gas, you know the oxidation reaction has started. Because this reaction is
highly exothermic, you will control the reaction by slowly adding the
cyclohexanone.
8. After you see the brown gas and you are certain the reaction has started, remove
the centrifuge tube from the sand bath and continue to add the cyclohexanone to
the centrifuge tube at a slow rate under the hood.
9. After all of the cyclohexanone has been added; reheat the centrifuge tube on the
sand bath for about one minute.
Heating drives the brown gas out of the solution; if this step is not
accomplished, the product will appear yellow from the brown gas as an impurity.
10. Place the centrifuge tube in a beaker on your lab bench. Allow the reaction
mixture to cool to room temperature. Crystals of adipic acid will form.
11. Recrystallize the crystals, if necessary, and collect them on a Hirsh funnel.
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12. Weigh the dry crystals and determine the percent yield.
13. Clean all glassware and return it to its storage location. Empty the hot sand
from the sand bath into a metal box and replace the heating mantel and rheostat to
their storage locations. Clean your desktop and show your product to the instructor.
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Oxidation Questions
Last name______________________, First name___________________
Show the major organic product for each of the following reactions.
OH
(1) KMnO4-/OH-
1.
(2) H+
2.
H
PCC
O
3.
H
CrO3/H+
O
4.
5.
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HNO3
O
OH
PCC
9
6. Show the reaction(s) with reagents necessary to convert your product in
problem 5 back to the starting material.
7. Show the products of the following reaction.
O3
(oxidative workup)
8. Draw the structure of the compound that would be obtained if the compound
shown below were oxidized with chromic acid (Jones).
O
HO
CHO
9. Explain why tert-butyl alcohol does not react with chromic acid.
10. Explain why secondary alcohols give ketones with PCC; whereas, primary
alcohols give aldehydes.
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