Paracetamol Synthesis for Active Learning of Amide Functional Groups in Undergraduate Chemistry Laboratories

Abstract

Three different experiments that allow the synthesis of the drug paracetamol are described; such experiments were designed for their implementation in undergraduate organic chemistry courses, considering the medical and economic importance of paracetamol. The experience wants to show the students some “real world” applications of organic synthesis techniques. The methods are based not only on the classical nucleophilic acyl substitution reaction but also on exploring innovative methodologies which expand the understanding of the reactivity of several organic functional groups, such as direct amidation of carboxylic acids under microwave heating and a transamidation reaction catalyzed by iron salts. The experiments allow students to obtain a compound of high interest and explore different synthesis, purification, and identification approaches. They work with molecules of biological significance and use various functional groups and organic synthesis techniques, including reflux heating, microwave heating, thin-layer and flash column chromatography, and IR and NMR spectroscopy. These experiments create a context in which it is possible to discuss various chemical concepts related to the reactivity of several functional groups. This is also to learn and illustrate the role of a catalyst and solid support in chemical processes.