Continuous flow upgrading of bio-based isobutene toward high value-added chemicals

Abstract

This work explores the generation of ethyl diazoacetate (EDA) and its cyclopropanation with isobutene under continuous flow conditions. In the first part, glycine ethyl ester hydrochloride, when subjected to a diazotization reaction, afforded EDA in good yields (70%) in flow. The formation of EDA was quantified by in-line infrared (IR) spectroscopy, which enabled fast and convenient optimization of the reaction conditions. In the second part, a screening of inexpensive and benign catalysts for the cyclopropanation of EDA with isobutene was carried out in batch. The latter can be obtained from bio-based sources, making this reaction especially appealing from a sustainability point of view. Subsequently, a preliminary investigation of flow conditions was conducted, showing great potential in a flow process involving the cyclopropanation of EDA in the future. Our investigations clear the path toward an environmentally-friendly preparation of cyclopropanes, which are in turn important building blocks for molecules such as Cilastatin, a key pharmaceutical deemed essential by the World Health Organization (WHO).