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.
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.
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 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.
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.
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.
Table 1. Oxidizing agents.
Mild Oxidizing Agents / Strong Oxidizing AgentsName / Formula / Name / Formula
Pyridinium
chlorochomate / PCC / Chromic acid or
Potassium dichromate / CrO3/H+
K2Cr2O7
Potassium
permanganate / KMnO4/OH-
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.
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.
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.
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 a-H atom is the one nearest the O atom in cyclohexanone. Replacing it with an –OH group gives an a-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 100-mL 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.
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.
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.
Oxidation Questions
Last name______, First name______
Show the major organic product for each of the following reactions.
8. Draw the structure of the compound that would be obtained if the compound shown below were oxidized with chromic acid (Jones).
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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Lab 7