Vol.:(0123456789)
Topics in Current Chemistry (2019) 377:2
https://doi.org/10.1007/s41061-018-0226-z
1 3
REVIEW
The Use of Molecular Oxygen for Liquid Phase Aerobic
Oxidations in Continuous Flow
Christopher A. Hone
1,2
· C. Oliver Kappe
1,2
Received: 16 November 2018 / Accepted: 3 December 2018 / Published online: 11 December 2018
© The Author(s) 2018, corrected publication 2019
Abstract
Molecular oxygen (O 2 ) is the ultimate “green” oxidant for organic synthesis. There
has been recent intensive research within the synthetic community to develop new
selective liquid phase aerobic oxidation methodologies as a response to the neces‑
sity to reduce the environmental impact of chemical synthesis and manufacture.
Green and sustainable chemical processes rely not only on effective chemistry but
also on the implementation of reactor technologies that enhance reaction perfor‑
mance and overall safety. Continuous flow reactors have facilitated safer and more
efficient utilization of O 2 , whilst enabling protocols to be scalable. In this article, we
discuss recent advancements in the utilization of continuous processing for aerobic
oxidations. The translation of aerobic oxidation from batch protocols to continuous
flow processes, including process intensification (high T/p), is examined. The use
of “synthetic air”, typically consisting of less than 10% O 2 in N 2 , is compared to
pure O 2 (100% O 2 ) as an oxidant source in terms of process efficiency and safety.
Examples of homogeneous catalysis and heterogeneous (packed bed) catalysis are
provided. The application of flow photoreactors for the in situ formation of singlet
oxygen (
1
O 2 ) for use in organic reactions, as well as the implementation of mem‑
brane technologies, green solvents and recent reactor solutions for handling O 2 are
covered.
Keywords Continuous flow · Flow reactor · Continuous processing · Aerobic
oxidation · Molecular oxygen · Process intensification · Membranes ·
Photochemistry · Green solvents
* C. Oliver Kappe
oliver.kappe@uni‑graz.at
http://ccflow.at
1
Center for Continuous Synthesis and Processing (CCFLOW), Research Center Pharmaceutical
Engineering (RCPE), Inffeldgasse 13, 8010 Graz, Austria
2
Institute of Chemistry, NAWI Graz, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria
67
Reprinted from the journal
Chapter 3 was originally published as Hone, C. A. & Kappe, C. O. Topics in Current Chemistry (2019)
.
377: 2. https://doi.org/10.1007/s41061-018-0226-z
Topics in Current Chemistry (2019) 377:2
https://doi.org/10.1007/s41061-018-0226-z
1 3
REVIEW
The Use of Molecular Oxygen for Liquid Phase Aerobic
Oxidations in Continuous Flow
Christopher A. Hone
1,2
· C. Oliver Kappe
1,2
Received: 16 November 2018 / Accepted: 3 December 2018 / Published online: 11 December 2018
© The Author(s) 2018, corrected publication 2019
Abstract
Molecular oxygen (O 2 ) is the ultimate “green” oxidant for organic synthesis. There
has been recent intensive research within the synthetic community to develop new
selective liquid phase aerobic oxidation methodologies as a response to the neces‑
sity to reduce the environmental impact of chemical synthesis and manufacture.
Green and sustainable chemical processes rely not only on effective chemistry but
also on the implementation of reactor technologies that enhance reaction perfor‑
mance and overall safety. Continuous flow reactors have facilitated safer and more
efficient utilization of O 2 , whilst enabling protocols to be scalable. In this article, we
discuss recent advancements in the utilization of continuous processing for aerobic
oxidations. The translation of aerobic oxidation from batch protocols to continuous
flow processes, including process intensification (high T/p), is examined. The use
of “synthetic air”, typically consisting of less than 10% O 2 in N 2 , is compared to
pure O 2 (100% O 2 ) as an oxidant source in terms of process efficiency and safety.
Examples of homogeneous catalysis and heterogeneous (packed bed) catalysis are
provided. The application of flow photoreactors for the in situ formation of singlet
oxygen (
1
O 2 ) for use in organic reactions, as well as the implementation of mem‑
brane technologies, green solvents and recent reactor solutions for handling O 2 are
covered.
Keywords Continuous flow · Flow reactor · Continuous processing · Aerobic
oxidation · Molecular oxygen · Process intensification · Membranes ·
Photochemistry · Green solvents
* C. Oliver Kappe
oliver.kappe@uni‑graz.at
http://ccflow.at
1
Center for Continuous Synthesis and Processing (CCFLOW), Research Center Pharmaceutical
Engineering (RCPE), Inffeldgasse 13, 8010 Graz, Austria
2
Institute of Chemistry, NAWI Graz, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria
67
Reprinted from the journal
Chapter 3 was originally published as Hone, C. A. & Kappe, C. O. Topics in Current Chemistry (2019)
.
377: 2. https://doi.org/10.1007/s41061-018-0226-z