Introducing an Organic Chemistry II Teaching Experiment: Mechanochemical Synthesis of Thiazoline Heterocycle

Only limited experimental designs for the synthesis of heterocyclic compounds are provided in current widely used Organic Chemistry Experiment textbooks, which cannot meet the practical needs of teaching. Under the concept of green chemistry, this study provides an innovative protocol for the synthesis of a thiazoline heterocycle from 1,4-dithiane-2,5-diol and 2-cyanopyridine via mechanochemical grinding with a common mortar. This experimental design demonstrates strong correlations with key theoretical concepts, including nucleophilic addition reactions of aldehydes and nitriles, the basicity of amines, and heterocyclic compounds. Moreover, not only essential laboratory techniques, such as mechanical grinding technology, recrystallization, and melting point determination, but also thin-layer chromatography (TLC) analysis and NMR characterization were incorporated in this protocol. In a word, some obvious advantages, such as distinct visual reaction progression, cost-effectiveness (∼0.02 USD (U.S. dollar) per student), simplified apparatus requirements (a simple mortar), good reproducibility, and a time-efficient protocol (3–4 class hours), make it particularly suitable for implementation in standard organic chemistry laboratory courses.