Synthesis of the Natural Product E -Anethole From Anisole

A multistep synthesis of E-anethole is described as a multi-week experiment for the undergraduate organic laboratory curriculum. The target molecule is a natural product that is present in several common spices and has an aroma that will be familiar to most students. The procedure utilizes reactions that are commonly covered as part of a standard second year organic chemistry curriculum. This can serve to reinforce lecture content in lab and lab content in lecture. The experiment starts with anisole and proceeds through three synthetic steps that include Friedel-Crafts acylation in step one, ketone reduction in step two, and alcohol dehydration in step three. The reactions provide opportunities for discussions about regioselectivity and stereoselectivity at each step. The procedure produces a 14:1 or greater molar ratio of E- and Z-anethole. Yields in the sequence are good to moderate and the reactions are complete in less than 30 minutes. Additionally, intermediates are isolated as pure substances that can be characterized without the need for time-consuming purifications. This enables the three-step synthetic sequence to be comfortably completed within two 3 h lab periods along with characterization of substances using IR spectroscopy, NMR spectroscopy, and gas chromatography. The experiment was carried out during the second semester of a standard yearlong organic chemistry sequence and student results are described.