11.4 Synthesis of Carboxylic Acids

Let’s review briefly some of the methods for preparing carboxylic acids that we’ve seen in previous chapters.

• Oxidation of a substituted alkylbenzene with KMnO₄ gives a substituted benzoic acid (Section 8.8). Both primary and secondary alkyl groups can be oxidized, but tertiary groups are not affected.

• Oxidation of a primary alcohol or an aldehyde yields a carboxylic acid (Section 9.8 and Section 10.3). Primary alcohols are often oxidized with the Dess Martin periodinane, and aldehydes are similarly oxidized with alkaline KMnO₄.

Hydrolysis of Nitriles

Carboxylic acids can be prepared from nitriles on heating with aqueous acid or base by a mechanism that we’ll discuss later in Chapter 11. Since nitriles themselves are usually made by S_N2 reaction of a primary or secondary alkyl halide with CN^–, the two-step sequence of cyanide displacement followed by nitrile hydrolysis is a good way to make a carboxylic acid from an alkyl halide (RBr → RC≡N → RCO₂H). Note that the product acid has one more carbon than the starting alkyl halide. One example occurs in a commercial route for the synthesis of the nonsteroidal anti-inflammatory drug ibuprofen. (See Chapter 8 Chemistry Matters.)Problem 11.9
How would you prepare CH₃CH₂CH₂CO₂H from CH₃CH₂CH₂Br?