Now showing 1 - 8 of 8
  • Publication
    A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic
    (Beilstein-Institut, 2017-11-29) ; ;
    An assembled suite of flow-based transformations have been used to rapidly scale-up the production of a novel auxin mimic-based herbicide which was required for preliminary field trials. The overall synthetic approach and optimisation studies are described along with a full description of the final reactor configurations employed for the synthesis as well as the downstream processing of the reaction streams.
      125Scopus© Citations 17
  • Publication
    Evaluating the Green Credentials of Flow Chemistry towards Industrial Applications
    Continuous flow chemistry is becoming an established technology platform that finds frequent application in industrial chemical manufacture with support and endorsements by the FDA for pharmaceuticals. Amongst the various advantages that are commonly cited for flow chemistry over batch processing, sustainability continues to require further advances and joint efforts by chemists and chemical engineers in both academia and industry. This short review highlights developments between 2015 and early 2021 that positively impact on the green credentials associated with flow chemistry, specifically when applied to the preparation of pharmaceuticals. An industrial perspective on current challenges is provided to whet discussion and stimulate further investment towards achieving greener modern synthetic technologies.
    Scopus© Citations 16  90
  • Publication
    Development of a Continuous Photochemical Benzyne-Forming Process
    A continuous-flow process is presented that enables the safe generation and derivatization of benzyne under photochemical conditions. This is facilitated by a new high-power LED lamp emitting light at 365 nm. The resulting flow process effectively controls the release of gaseous by-products based on an adjustable backpressure regulator and delivers a series of heterocyclic products in a short residence time of 3 minutes. The robustness of this methodology is demonstrated for the rapid generation of benzotriazoles, 2 H -indazoles and various furan-derived adducts, facilitating the preparation of these important heterocyclic scaffolds via a simple and readily scalable flow protocol.
      51Scopus© Citations 11
  • Publication
    Overcoming the Hurdles and Challenges Associated with Developing Continuous Industrial Processes
    Continuous flow chemistry is often viewed as a very simple concept on paper, however scientists with significant flow chemistry experience will highlight a number of challenges that need to be overcome. Critical for the successful development of any flow process is a high level of understanding of potential pitfalls that may be encountered. A collaborative and multi-disciplinary team of chemists and chemical engineers is essential in the development of a process from lab scale through to production. This Minireview will identify and highlight relevant risks and their subsequent mitigation strategies to ensure successful flow processing.
    Scopus© Citations 32  35
  • Publication
    A Perspective on Continuous Flow Chemistry in the Pharmaceutical Industry
    (American Chemical Society, 2020-01-10) ; ; ;
    Continuous flow manufacture is an innovative technology platform, which is gaining momentum within the pharmaceutical industry. The key advantages of continuous flow include faster and safer reactions, which can be more environmentally friendly, smaller footprint, better quality product, and critically, the ability to perform chemistry that is difficult or impossible to do in batch mode. Globally, significant efforts have been made to develop the manufacturing flexibility and robustness of processes used to produce chemicals in a continuous way, yet despite these scientific developments, a major challenge for industry is the established application of flow technology to commercially relevant examples. The identification of opportunities to apply flow solutions to current processes is also critical to the success of this new technology for pharmaceutical and fine chemical companies. This review highlights industrial hurdles and the importance of education and showcases recent (2018-2019) and relevant industrial examples where utilization of flow technology has been successfully performed.
    Scopus© Citations 289  1452
  • Publication
    Continuous Flow Synthesis of Quinolines via a Scalable Tandem Photoisomerization-Cyclization Process
    A continuous photochemical process is presented that renders a series of quinoline products via an alkene isomerization and cyclocondensation cascade. It is demonstrated that a high-power LED lamp generates the desired targets with higher productivity and efficiency than a medium-pressure Hg-lamp. The scope of this tandem process is established and allows for the generation of various substituted quinolines in high yields and with throughputs of greater than one gram per hour. Finally, this effective flow process is coupled with a telescoped hydrogenation reaction to render a series of tetrahydroquinolines including the antimalarial natural product galipinine.
    Scopus© Citations 25  274
  • Publication
    Development of a Telescoped Flow Process for the Safe and Effective Generation of Propargylic Amines
    Propargylic amines are important multifunctional building blocks that are frequently exploited in the synthesis of privileged heterocyclic entities. Herein we report on a novel flow process that achieves the safe and effective on-demand synthesis of propargylic amines in a telescoped manner. This process minimizes exposure to hazardous azide intermediates and renders a streamlined route into these building blocks. The value of this approach is demonstrated by the rapid generation of a small selection of drug-like thiazolines that result from a high-yielding reaction cascade between propargylic amines with different aryl isothiocyanates.
    Scopus© Citations 5  155
  • Publication
    Continuous Flow Synthesis of Cyclobutenes Using LED Technology
    Cyclobutenes are highly strained ring systems of considerable synthetic interest that can be accessed via cycloaddition reactions between alkenes and alkynes. However, their traditional preparation relies on photochemical [2+2]-cycloadditions that exploit low wavelength UV radiation emitted from inefficient medium-pressure Hg-lamps. This paper reports on the development of a modern approach using a high-power LED set-up emitting at the boundary of UV-A and visible light in conjunction with a continuous flow reactor. The resulting flow process renders a series of cyclobutenes from maleimides and various commercial alkynes. This provides a more energy-efficient approach that is readily scalable to access multigram quantities of cyclobutenes in high chemical yields and short residence times. The value of these products is exemplified by flow-based hydrogenations yielding highly substituted cyclobutanes which represent sought after building blocks in modern medicinal chemistry programs.
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