Oxidation of Alcohols
Introduction
The conversion of alcohols into aldehydes and ketones is one of the most common and most useful transformations available to the synthetic organic chemist. The general features of this oxidation reaction are outlined in Figure 1.
Figure 1
The Oxidation of Alcohols
A synonym for the oxidation of alcohols, dehydrogenation, suggests the structural feature that is required for this process: H-C-O-H. The OH group must be attached to a carbon atom that is bonded to at least one hydrogen atom. In other words, oxidation of alcohols involves the 1,2-elimination of "the elements of" dihydrogen, H and H.
Exercise 1 Select the proper outcome in each of the following reactions. Draw the structure of the product in those cases where you determine that a reaction will occur. (The symbol [O] represents an oxidizing reagent.]
aldehyde ketone no reaction
aldehyde ketone no reaction
aldehyde ketone no reaction
aldehyde ketone no reaction
aldehyde ketone no reaction
aldehyde ketone no reaction
This structural requirement means that 3
o alcohols do not normally undergo oxidation. All of the alcohols shown below will not undergo oxidation under reaction conditions where 1
o and 2
o alcohols react readily.
Oxidizing Agents
There is a wide variety of reagents that are used for the oxidation of alcohols. Two of the most common are chromic acid, H2Cr2O7, and pyridinium chlorochromate, PCC. Chromic acid is prepared by treatment of sodium or potassium dichromate with aquesous sulfuric acid as shown in Equation 1.
Chromic acid is most commonly used to oxidize 2o alcohols to ketones. One example is given in Equation 2.
Pyridinium chlorochromate is made by mixing chromium trioxide with pyridine and hydrochloric acid as indicated in Equation 3. The oxidizing component of PCC is the chlorochromate anion, CrClO3-.
PCC was developed especially for the oxidation of 1o alcohols to aldehydes, a transformation which is difficult to accomplish using chromic acid because aldehydes react rapidly with aqueous chromic acid to produce carboxylic acids.
Figure 2 compares the oxidation of 2-phenylethanol by chromic acid and PCC.
Figure 2
Oxidation Alternatives
Exercise 2 What is the oxidation level of the 1
o carbon in 2-phenylethanol?
What is the oxidation level of the carbonyl carbon in phenylacetaldehyde?
What is the oxidation level of the carboxyl carbon in phenylacetic acid?
Exercise 3 Water will add to the carbonyl group of aldehydes in a manner similar to that observed in the hydration of alkenes. Write an equation depicting the addition of the "elements of" water to phenylacetaldehyde. Does this product meet the structural requirements for oxidation?
Mechanism
Oxidation of alcohols is basically a two step process. The first step involves the formation of chromate esters. In our discussion of esterification, we saw that alcohols react with carboxylic acids, phosphoric acid, and sulfonic acids to produce various types of esters. The same is true for chromic acid and PCC; they react with alcohols to produce chromate esters. Once the chromate ester is formed, it undergoes an elimination reaction to generate the carbonyl group of the aldehyde or ketone. These two steps are outlined in Figure 3.
Figure 3
The Mechanism of Chromate Oxidations
Examples
The oxidation of the secondary alcohol menthol to the ketone menthone, as outlined in Equation 4, provides a simple example of a dichromate oxidation. The product is formed in over 90% yield.
Equation 6 presents a variation on the theme discussed above. In this reaction the oxidizing agent is chromium trioxide, CrO3 dissolved in acetic acid. It converts a 2o alcohol into a ketone. This oxidation is part of a multi-step synthesis of a terpene called longifolene, which is a component of pine oil.
Synthetic chemists often pursue exotic targets. The synthesis of sirenin, Equation 6, offers a case in point. A key step in the multi-step synthesis of this material was the PCC oxidation of a 1o alcohol to an aldehyde.
Sirenin is the sperm attractant from the female gametes of a water mold. Now that's exotic.
