Getting the Classroom Closer to Research Work: Undergraduate Students Prepare N-Hexylcinnamamide

Amides are usually prepared using amines and acyl halides, which often implies a two-step procedure. Alternatively, coupling reagents can be used in a single-step reaction with good yields, which seems to be suitable for organic chemistry laboratory classes. This work was designed to synthesize N-hexylcinnamamide through a one-step reaction from cinnamic acid using the coupling reagent benzotriazol-1-yloxytri(pyrrolidino)phosphonium hexafluoro-phosphate (PyBOP). The purification of N-hexylcinnamamide, using various laboratory techniques, as well as its structural elucidation by spectroscopic methodologies, is also addressed. In addition, the theoretical partition coefficient (log P) values of N-hexylcinnamamide and of cinnamic acid are predicted. The proposed experiment is developed in three laboratory classes and is planned for second-year undergraduate students. In summary, it is expected that students broaden their knowledge about amide synthesis, laboratory techniques, and spectroscopic characterization, especially IR and NMR. Besides the pedagogical enhancements, this activity also allows students to be in contact with research work based on the chemical modification of natural products according to a medicinal chemistry approach.