2-Hydroxybenzoic acid, or salicylic acid (SA), is among the most important medicinal compounds ever discovered. Since ancient times, humans have benefited from the therapeutic effects of naturally occurring SA precursors, which readily metabolize to SA and provide analgesic, anti- inflammatory and antipyretic benefits. Today, synthetic SA continues to play an important role as an active ingredient in over-the-counter (OTC) topical drug products and as a precursor to other drug compounds such as aspirin (acetylsalicylic acid), methyl salicylate and the sunscreen actives homosalate and octisalate. SA is also a critical starting material for the synthesis of certain fragrance ingredients, including benzyl salicylate and isoamyl salicylate.
SA, shown in Figure 1, is the ortho isomer of monohydroxybenzoic acid. It is commonly referred to as a beta hydroxy acid due to the location of its hydroxyl (–OH) group, which is two carbons away from the carboxylic acid (–COOH) group. SA is a relatively small molecule with the chemical formula C7H6O3, corresponding to a molecular weight of 138.12 g/mol. It is more acidic than most organic acids; for example, the pKa of SA is 3.0 whereas the pKa of the unsubstituted benzoic acid is 4.2. This increased acid strength is due to the location of the electron-withdrawing –OH group on its aromatic ring, which promotes dissociation of the –COOH group at lower pH values.