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Flow Chemistry for the Synthesis of Heterocycles pp 161–186Cite as

Flow-Assisted Synthesis of Heterocycles at High Temperatures

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Part of the book series: Topics in Heterocyclic Chemistry ((TOPICS,volume 56))

Abstract

Performing selective and high-yielding transformations on complex organic molecules at temperatures in the range of 200–450°C may at first seem counterintuitive or even impossible. However, using continuous flow systems, conditions of this sort are indeed accessible and viable for useful chemistry. This review highlights recent endeavors in heterocycle synthesis and modification enabled by high-temperature (>200°C) flow chemistry, with emphasis placed on showcasing the variety and synthetic utility of different high-temperature enabled transformations. The reviewed content naturally falls into three categories: pericyclic transformations, condensation reactions, and modification/functionalization of heterocycles. Different shortcomings and considerations necessary when planning high-temperature flow reactions have also been highlighted where applicable.

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Notes

  1. 1.

    Depending on the functionalization: 180°C for methyl silicone oils and 230°C for phenyl methyl silicone oils.

  2. 2.

    Sulfinert is a Siltek-treated stainless steel coil (i.e., chemical vapor deposition multilayer silica coating) that has the advantages of Teflon coatings or glass/fused silica coils without the temperature limitations and gas permeability concerns of Teflon and with much greater flexibility and temperature stability than glass or fused silica coils. For more information, see www.Restek.com.

  3. 3.

    The ionic constant (K w ) of scH2O is highly pressure dependent and can be greater than that of subcritical water at high pressures, i.e., both [H3O+] and [OH−] can be higher in scH2O at high pressures.

  4. 4.

    The critical point of water is 374°C, 218 bar. At 400°C, 150 bar, the water is present as superheated steam but not yet as a supercritical fluid.

  5. 5.

    When keeping the temperature constant at 400°C, K w is at a minimum when P = 250 bar.

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Authors and Affiliations

  1. Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON, Canada

    Ryan J. Sullivan & Stephen G. Newman

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  1. Ryan J. Sullivan
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  2. Stephen G. Newman
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Correspondence to Stephen G. Newman .

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Editors and Affiliations

  1. Department of Chemistry, University of Leuven (KU Leuven), Leuven, Belgium

    Upendra K. Sharma

  2. Department of Chemistry, University of Leuven (KU Leuven), Leuven, Belgium

    Erik V. Van der Eycken

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Sullivan, R.J., Newman, S.G. (2018). Flow-Assisted Synthesis of Heterocycles at High Temperatures. In: Sharma, U., Van der Eycken, E. (eds) Flow Chemistry for the Synthesis of Heterocycles. Topics in Heterocyclic Chemistry, vol 56. Springer, Cham. https://doi.org/10.1007/7081_2018_18

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