(421g) Increased Efficiency in Chemical Process R&d by Automation - the Discovery of An Innovative and Extremely “Green” One-Step Synthesis of Tetronic Acid

Tetronic acid is an important key intermediate for different chemical products (e.g. (+)-Biotin and Losigamon) of the fine chemical and pharmaceutical industry. The industrial production of tetronic acid can be achieved in a multi-step gas phase process, starting from 4-chloro aceto-acetate. It was found, that addition of 4-chloro acetoacetate to a cold, aqueous solution of sodium hydroxide yields a mixture of sodium chloroacetate and sodium acetate. In addition, the resulting yield of sodium tetronate is less than 30%. Based on these findings, an innovative one-step process for the synthesis of tetronic acid was targeted. Therefore, the pH and temperature dependency of this reaction was studied in a parallel, automated set of experiments. This study resulted in an innovative and extremely ?green? process, which saves several chemical steps over the pre-existing industrial synthesis of tetronic acid, and may yield to major cost savings in the production of this important intermediate.

This and other relevant examples, presented herein, impressively support the enormous value of a parallel and automated High Output Experimentation approach.