Synthesis of Paracetamol through Free-Radical Reactions: An Educational Approach in Organic Chemistry

Acquiring the skills to improve synthetic techniques used in research and industry is one of the most critical goals for chemists in training. Achieving this requires not only a solid foundation in chemistry but also creativity and a deep understanding of the physicochemical processes involved in experimental work. This experimental activity is designed to guide students in developing a novel synthetic technique for producing paracetamol, which is a widely used pharmaceutical compound. Students are encouraged to first rationalize the key steps in the currently used procedures, identifying potential limitations and areas for improvement. This laboratory synthesis is specifically intended for second-semester organic chemistry students. Through bibliographic research and group brainstorming, they then proposed a new reaction pathway based on free-radical chemistry. Using their acquired knowledge and the transition wavelengths of the compounds involved, students design an appropriate experimental setup based on irradiation of electromagnetic waves in the UV region. This innovative approach employs commercial reagents, such as 4-aminophenol and acetyl chloride, and achieves a reaction time of just 15 min with yields exceeding 70%, outperforming other synthetic methods reported in the literature. The purity and chemical structure of the synthesized paracetamol were confirmed through 1H nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (DART method), and melting point analysis.