Synthesis of value-added intermediates by continuous flow technology

• Main Author: Smith, Laura Katherine
• Published: Durham University 2018
• Subjects: 540
• Online Access: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.738609

We present three projects linked by our use of continuous flow chemistry in the synthesis of organic intermediates. The first is the synthesis of 1,1'-spirobiindane-7,7'-diol (SPINOL) in 6 steps and 32% overall yield. The synthesis has been improved over the previous literature protocols as it is safer, scalable, and higher-yielding, with better robustness and reproducibility. We introduce two attempts towards the enantioselective synthesis of SPINOL. In the second project, we have developed a flow process based on the Vapourtec reactor to synthesise coumalic acid and methyl coumalate from malic acid in concetrated sulfuric acid. A new heated rotating flow reactor is also presented for the intensified synthesis of coumalic acid, a valuable intermediate in organic synthesis derived from biorenewable sources of malic acid. Methyl coumalate has been used in two Diels-Alder reactions where the products have applications in molecular electronics and organic light-emitting diodes. Finally, the Darzens reaction for the synthesis of epoxides is presented here for the first time in flow, providing access to a range of benzaldehyde-derived products, including precursors to the pharmaceutical compound ibuprofen.