Process Development of the Weiss–Cook Reaction for the Preparation of cis-1,5-Dimethylbicyclo[3.3.0]octane-3,7-dione in the Undergraduate Organic Laboratory

Abstract

A four week laboratory experiment was designed on the basis of a modification of the Weiss–Cook reaction for the preparation of cis-1,5-dimethylbicyclo­[3.3.0]­octane-3,7-dione. In general, this very versatile organic reaction involves a two-step process reacting biacetyl with 2 mol of dimethyl-1,3-acetonedicarboxylate to form cis-bicycle­([3.3.0]­octane-3,7-dione). The reaction employs an aldol reaction followed by successive Michael reactions that are typically encountered near the end of a second-year undergraduate organic chemistry course. The students gained hands-on experience with 1H NMR and IR spectroscopy to analyze the intermediate and final product. Students wrote a formal laboratory report and discussed their results, including a proposal of the reaction mechanism and calculation of the overall yield. The experiment may be used in a traditional second semester organic chemistry laboratory or an advanced organic chemistry synthesis course on multigram or microscale levels.