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Acylated aromatic esters and amines are important ingredients of over-the-counter headache remedies. As such, the synthesis and analysis of aspirin, a common analgesic, has been widely used in the undergraduate introductory chemistry laboratory curriculum for many years (1). The synthesis is typically carried out under reflux conditions to ensure that a good yield of the desired product is obtained.
Here we report a microwave-enhanced synthesis of aspirin, acetanilide, phenacetin, and acetaminophen (see Scheme I for synthesis of phenacetin). The reactions are conveniently carried out in a microwave oven at 30% power for five minutes. Good to excellent yields of the desired analgesic products are obtained on recrystallization of the initially isolated crude solids. Identity and purity of the product are confirmed by melting points, thin-layer chromatography, and infrared spectroscopy.
Microwaves have been used extensively in a variety of applications (2), including rapid synthesis of organic compounds (3). This experiment complements the previously published use of microwave irradiation to facilitate chemical reactions in the undergraduate laboratory curriculum (4).
Acetylsalicylic acid (aspirin) was synthesized from salicylic acid and acetic anhydride with phosphoric acid as the catalyst. The mixture was microwaved at 30% power for five minutes. Recrystallization from toluene resulted in a 75% yield of a pure aspirin product. Melting points, IR, and TLC all confirmed the identity and purity of the aspirin product (see experimental section). Further, ferric chloride gave a negative test, indicating the absence of salicylic acid.
The other drugs (acetanilide, acetaminophen, and phenacetin) were prepared by reacting acetic acid with aniline, paminophenol, and p-phenetidine, respectively. All reactions were carried out under the same experimental conditions as aspirin except that W 7.5 mL of water replaced the acid catalyst, (ii) the amount of acetic anhydride was reduced to 0.02 mol, and (iii) the reaction time for preparation of acetanilide was reduced to three minutes. The yields of acetanilide, acetaminophen, and phenacetin were 73%, 56%, and 81%, respectively. There are many advantages to synthesizing organic compounds by...