Challenging Ozonolysis

Lead Research Organisation: University College London
Department Name: Chemical Engineering

Abstract

This proposal is aimed at delivering breakthrough technology for exploiting a number of potentially very valuable reactions that are rarely used in the pharmaceutical industry due to constraints posed by conventional laboratory hardware. The focus is on ozonolysis reactions which are characterised by minimal environmental impact and high efficiency. In spite of these attributes they have not found widespread applications due to safety concerns. Micro channel continuous flow reactors offer an excellent solution to these issues. This is due mainly to the small distances present for mass / heat transfer and quenching, and improved heat management. Ozonolysis is an example of multiphase reactions with fast kinetics and high exothermicity, which can not be performed currently in commercially available flow chemistry systems. In multiphase reactions, reactants from one phase have to pass through an interface, dissolve and then react in another phase. Transport phenomena play a crucial role in reaction performance. Thus, the behaviour of the reaction (which is the prime domain of the chemist) is inexorably linked with transport phenomena (which are the prime domain of the chemical engineer). For this reason, successful development of flow chemistry systems and protocols for multiphase reactions requires input from both disciplines.In this proposal we endeavour to develop novel, easy to use, intrinsically safe, continuous flow, microchannel reactor systems, via collaboration between two research teams with strong track records in organic synthesis and microreaction technology and two industrial partners with expertise in medicinal chemistry and flow chemistry instrumentation. Based on the chemistry of ozone as a hydride acceptor, we aim to identify and exploit completely new, greener, highly efficient and less laborious synthesis pathways that can be employed to manufacture high value compounds of relevance to the pharmaceutical industry from inexpensive raw materials.

Publications

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Roydhouse M (2013) Ozonolysis of some complex organic substrates in flow in RSC Advances

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Roydhouse M (2011) Ozonolysis in Flow Using Capillary Reactors in Organic Process Research & Development

 
Description We designed microchannel reactor systems that operated under unconventional flow regimes with excellent mass transfer characteristics for ozonolysis reactions. We demonstrated the conversion of decene (as a model system) as well as various compounds of relevance to pharmaceutical industry. The mean residence times were found to be dependent on the liquid flow rates and independent of the gas flow rates within the flow rates studied. The flow patterns at different gas/liquid ratios were obtained. Microchannel devices for the separation of the gas and liquid at the outlet of the reactors were designed, modelled and evaluated.
Exploitation Route The knowledge gained and the flow systems developed from this work can form the basis of cleaner, less laborious and cheaper chemical transformations. They can broaden the scope of synthetic transformations to other multiphase reactions particularly of fast kinetics and highly exothermic nature such as halogenations, hydrogenations, carbonylations, sulfonations, nitrations, phase transfer catalysis, as well as multiphase flow purification techniques such as extractions.
Sectors Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description A nine month placement within GSK was carried out, demonstrating the utility of the approach. The ozonolysis flow equipment was used in the synthesis of several key medicinal targets including an intermediate, of significant importance, unobtainable by conventional synthetic routes. Alkenes, furans and quinolines were ozonised to give good- excellent isolated yields. Given the utility and convenience of this approach, GSK took the decision to put together an in-house ozonolysis flow set-up based on the UCL approach.
First Year Of Impact 2012
Sector Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description UCL/EPSRC Collaborative Training Account
Amount £23,714 (GBP)
Funding ID Enterprise Secondment Award 
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 01/2011 
End 09/2011
 
Description 3rd European Process Intensification Conference, Manchester, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact interest from industry and other universities in our research outcome
Year(s) Of Engagement Activity 2011
URL http://www.icheme.org/events/conferences/past-conferences/2011/european%20process%20intensification%...
 
Description 1st RSC/SCI Symposium on Continuous Processing and Flow Chemistry,Stevenage, UK 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Interest from industrial partners about the outcome of our research
Year(s) Of Engagement Activity 2010
URL http://www.soci.org/news/fine-chems/fine-chemicals-flow-chem-2010-past-papers
 
Description 2nd RSC/SCI Symposium on Continuous Processing and Flow Chemistry, Novartis, Horsham, UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact interest from industrial partners and other universities in the outcomes of our research. It led to continuation of the work after the period considered for the grant.
Year(s) Of Engagement Activity 2013
URL http://www.rsc.org/events/detail/9589/2nd%20SCI/RSC%20Symposium%20on%20Continuous%20Processing%20and...