Integrated Multistep Photochemical and Thermal Continuous Flow Reactions: Production of Bicyclic Lactones with Kilogram Productivity

Rowena A. Howie, Luke D. Elliott, Surajit Kayal, Xue Zhong Sun, Magnus W.D. Hanson-Heine, Jonathan Hunter, Charlotte A. Clark, Ashley Love, Christopher Wiseall, Darren S. Lee, Martyn Poliakoff, Kevin I. Booker Milburn, Michael W. George

Research output: Journal PublicationReview articlepeer-review

2 Citations (Scopus)

Abstract

Combining continuous photochemistry and flow reactions in high-temperature/high-pressure water has enabled us to integrate a multistep sequence into a single process with a reduction in reaction time to <10 min compared to >24 h in batch. At the same time, applying this approach to different substrates has allowed us to increase previously low yields to levels high enough to make these reactions potentially useful for multistage synthesis. In this paper, we describe the [2 + 2] cycloaddition/fragmentation of 3,4,5,6-tetrahydrophthalic anhydride and propargyl alcohol and analogous compounds leading to bicyclic lactones to demonstrate how photochemistry and thermal chemistry can be combined using continuous flow techniques to create complex structures on a relatively large scale. We show how photochemical and high-temperature water flow reactors can be used to carry out a three-step reaction sequence as a single integrated and continuous process. The reaction time has been reduced by exploiting the enhanced acidity of high-temperature water/acetonitrile mixtures. The overall process is demonstrated on an equivalent productivity of a >1 kg/day productivity using lab-scale equipment. Our approach should be simple to scale up in an appropriate facility, for larger scale production of chemicals. Process analytical technology and modeling were used to support the reaction development, while UV and IR time-resolved spectroscopies have been used to provide a deeper understanding of the reaction mechanism.

Original languageEnglish
Pages (from-to)2052-2059
Number of pages8
JournalOrganic Process Research and Development
Volume25
Issue number9
DOIs
Publication statusPublished - 17 Sep 2021
Externally publishedYes

Keywords

  • flow chemistry
  • integrated chemical processes high-temperature water
  • organic photochemistry

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Integrated Multistep Photochemical and Thermal Continuous Flow Reactions: Production of Bicyclic Lactones with Kilogram Productivity'. Together they form a unique fingerprint.

Cite this