17.7 Oxidation of Alcohols

Perhaps the most valuable reaction of alcohols is their oxidation to give carbonyl compounds—the opposite of the reduction of carbonyl compounds to give alcohols. Primary alcohols are oxidized either to aldehydes or carboxylic acids, and secondary alcohols are oxidized to ketones, but tertiary alcohols don’t normally react with most oxidizing agents.

Primary and secondary alcohols can be oxidized by any of a number of reagents, including CrO3 in aqueous acetic acid and KMnO4 in aqueous NaOH, but chromium-based reagents are rarely used today because of their toxicity and fire danger. Today, primary and secondary alcohols are oxidized to aldehydes and ketones, respectively, using the iodine- containing Dess–Martin periodinane in dichloromethane solution.

Primary alcohols are oxidized to carboxylic acids by heating with KMnO4 in a basic aqueous solution. An aldehyde is involved as an intermediate in the KMnO4 reaction but can’t usually be isolated because it is further oxidized too rapidly.

All these oxidations occur by a mechanism that is closely related to the E2 reaction (Section 11.8). In the Dess–Martin oxidation, for instance, the first step involves a substitution reaction between the alcohol and the I(V) reagent to form a new periodinane intermediate, followed by expulsion of reduced I(III) as the leaving group. Similarly, when a Cr(VI) reagent, such as CrO3, is the oxidant, reaction with the alcohol gives a chromate intermediate followed by expulsion of a reduced Cr(VI) species.

Biological alcohol oxidations are the opposite of biological carbonyl reductions and are facilitated by the coenzymes NAD+ and NADP+. A base removes the –OH proton, and the alkoxide ion transfers a hydride ion to the coenzyme. An example is the oxidation of sn– glycerol 3-phosphate to dihydroxyacetone phosphate, a step in the biological metabolism of fats (Figure 17.9). Note that addition occurs exclusively on the Re face of the NAD+ ring, adding a hydrogen with pro-R stereochemistry.

Figure 17.9 The biological oxidation of an alcohol (sn-glycerol 3-phosphate) to give a ketone (dihydroxyacetone phosphate). This mechanism is the exact opposite of the ketone reduction shown previously in Figure 17.5.

Problem 17-14

What alcohols would give the following products on oxidation? (a)

(b)

(c)

Problem 17-15

What products would you expect from oxidation of the following compounds with the Dess–Martin periodinane?

(a)

• Hexanol (b)
• Hexanol (c) Hexanal