Facile and Greener Mechanochemical Synthesis of Paracetamol: An Easy-to-Perform and Much-to-Learn Experiment for Secondary and Postsecondary Students

Abstract Paracetamol is a well-known drug used as analgesic and antipyretic. The synthesis of paracetamol is an important experiment in the syllabi of secondary and postsecondary courses of different universities, world over. Generally, it is prepared by reacting p-aminophenol with acetic anhydride in the presence of a catalytic amount of pyridine and sulfuric acid. The usage of pyridine and sulfuric acid makes the synthesis hazardous and therefore, unsafe for students. Green chemistry is being taught as a core paper to secondary and postsecondary students, globally. Green chemistry approaches can be employed for the laboratory synthesis of paracetamol, whereby the use of pyridine and acid can be avoided to make the reaction comparatively safer for students. Taking into account the importance of green chemistry approaches and the synthesis of paracetamol as a laboratory experiment, this paper reports a facile and greener mechanochemical laboratory experiment for the synthesis of paracetamol by reacting p-aminophenol with acetyl chloride. The identification of the synthesized paracetamol was ascertained by comparison of its physical properties (physical state, appearance, melting point, and solubility) and chromatographic properties (thin-layer chromatography) with paracetamol extracted from Dolo-650 tablets. In addition, the identification of paracetamol was ascertained by simple chemical tests (ferric chloride and oxidation with potassium dichromate). This experiment serves as an interesting instructive approach for understanding mechanochemical organic synthesis, green chemistry, drug extraction from solid dosage formulations, identification of organic drugs from property comparison with standard drugs, and simple chemical tests without using high-end characterization techniques.