2- Hydroxybenzoic acid from aspirin

Conversion of Acid Anhydrides into Esters Acetic anhydride is often used to prepare acetate esters from alcohols. For example, aspirin (acetylsalicylic acid) is prepared commercially by the acetylation of o-hydroxybenzoic acid (salicylic acid) with acetic anhydride. 

In a synthesis reaction, an impure sample of aspirin was prepared from 2-hydroxybenzoic acid and ethanoic anhydride. The reaction mixture was heated for approximately 10 minutes. 

The ethanoyl derivative of 2-hydroxybenzoic acid is better known as aspirin and is prepared from the acid with ethanoic anhydride, using sulfuric acid as catalyst ... 

Towards the end of the 19th century, the German dye industry embarked on diversification based on its coal-tar intermediates. These became important medicinal products, including Bayer s aspirin, made from the intermediate salicylic acid (o-hydroxybenzoic acid). The first local anesthetics were esters of aminobenzoic acid. In 1906, Hoechst introduced the anesthetic novocaine (45), marketed as the hydrochloride of diethylaminoethyl p-aminobenzoate, based on the research of Alfred Einhom. Novocaine was the standard... 

Vermeersch and co-workers have reported the case of a 4-month-old girl who presented with agitation, hyperexcitation, fever, dehydration, polypnea and metabolic acidosis. H NMR spectroscopy of the lyophilized urine from the patient showed the presence of 2-hydroxybenzoic acid (salicylic acid), o-hydroxyhippuric acid and 2,5-dihydroxyhippuric acid, which indicated that she had been poisoned with salicylate (aspirin). It is notable that this study was completed at 80 MHz, a relatively low field strength. 

One such possibility is the use of microwave ovens as the heating supply, and a method for synthesizing aspirin (2-ethanolyoxybenzoic acid) has been devised using such an oven. The method starts from 1-hydroxybenzoic acid and the esterification procedure used is outlined in Figure 20.83. 

Aspirin, prepared industrially by selective electrophilic aromatic substitution of phenol, is arguably the blockbuster drug of all times. Its active metabolite, 2-hydroxybenzoic acid (salicylic acid), obtained from the bark of the white willow tree, has been used for four millennia for the treatment of inflammation and to relieve pain or discomfort caused by arthritis, soft-tissue injuries, and fever. Aspirin was discovered by the German company Bayer in the late 19th century and ironically marketed together with another drug, heroin, whose addictive side effects were not recognized then. 

Salicylates are derivatives of 2-hydroxybenzoic acid (salicylic acid). They were discovered in 1838, following the extraction of salicylic acid from willow bark. Salicylic acid was used medicinally as the sodium salt but replaced therapeutically in the late 1800s by the acetylated derivative, acetylsalicylic acid (ASA), or aspirin (Figure 13.2). Therapeutie utility is enhanced by esterification of the phenolic (hydroxyl) group as in aspirin, and by substitution of a hydrophobic/lipophilic group at C-5 as in diflimisal. 

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