(507d) Heuristics for Implementing Photoredox Catalysis in Flow Reactors
AIChE Annual Meeting
2017
2017 Annual Meeting
Catalysis and Reaction Engineering Division
Reaction Engineering in Pharmaceuticals and Fine Chemicals
Wednesday, November 1, 2017 - 9:00am to 9:20am
Heuristics
for Implementing Photoredox Catalysis in Flow Reactors Eric
G. Moschetta,* Steven M. Richter, and Steven J. Wittenberger AbbVie,
Inc. Process R&D, 1401 Sheridan Road North Chicago, IL 60064 *corresponding
author: eric.moschetta@abbvie.com Photoredox
catalysis is reemerging in organic synthesis as a powerful method for
constructing small molecules under mild conditions. Such transformations often
employ transition metal catalysts to absorb visible light, exciting the
catalysts into energetic states that facilitate single electron transfer events
between the catalysts and organic substrates.[1] These reactions
frequently occur at mild temperatures, including room temperature, using
visible light sources such as LEDs that provide intense light with narrow
wavelength emissions. As such, materials for conducting photoredox chemistry at
the lab scale are readily available for chemists and engineers. However,
significant challenges remain in visible-light photoredox catalysis. The
primary challenge in industrial applications is scaling up photoredox reactions
from laboratory scale batch reactors to reactors that are capable of
multi-kilogram scale production. Proper reactor design relies on rigorous
understanding of the inherent kinetics of photoredox reactions, which are
largely unexplored. The photon flux, the overall observed rate at which photons
are received in the reactor, must be high enough to ensure that the inherent
kinetics of the reaction are the operating conditions of the reactor. The
lamp-reactor geometry, therefore, is a critical design factor in scalable
photoredox flow chemistry. Maximizing the photon flux also likely depends on
careful tuning of the catalyst concentration, reactant concentration, and light
intensity. Continuous
flow reactors can facilitate improved photon fluxes and increased throughput
through significantly decreased reaction times compared to batch reactions,
which are both necessary for industrial photoredox catalysis.[2] Flexible
fluoropolymer tubing is chemically resistant to many materials and highly
transparent to visible light, meaning that tubing can be wrapped around light
sources such as LEDs for access to customizable tubular flow reactors for
photoredox applications. The short tube diameters allow for shorter path
lengths, meaning that photons are more evenly distributed throughout the
reactor, increasing the apparent rate of reaction. However, general principles
and heuristics for designing such flow reactors are not yet available to
process chemists and engineers. This work establishes heuristics for employing
flow reactors in photoredox chemistry. The effects of reactant and catalyst
concentration, tube diameter, and LED intensity on the observed photon fluxes
and rates of reaction will be discussed. The model reaction for establishing
the heuristics will be the oxidation of 9,10-diphenylanthracene using molecular
oxygen and a common ruthenium photoredox catalyst, Ru(bpy)3Cl2.
The quantum yield for this reaction is known,[3] meaning that the
photon flux under a given set of reaction conditions can be calculated directly
once the rate of reaction is measured. These heuristics will then be examined
against a pyrazole synthesis driven by photoredox catalysis, using the same
ruthenium catalyst, to see if heuristics accurately predict how the observed
rates of reaction change with changes in reaction conditions in flow. References
abstract presentation was sponsored by AbbVie. AbbVie contributed to the
design, research, and interpretation of data, writing, reviewing, and approving
the publication. All authors are AbbVie employees.
for Implementing Photoredox Catalysis in Flow Reactors Eric
G. Moschetta,* Steven M. Richter, and Steven J. Wittenberger AbbVie,
Inc. Process R&D, 1401 Sheridan Road North Chicago, IL 60064 *corresponding
author: eric.moschetta@abbvie.com Photoredox
catalysis is reemerging in organic synthesis as a powerful method for
constructing small molecules under mild conditions. Such transformations often
employ transition metal catalysts to absorb visible light, exciting the
catalysts into energetic states that facilitate single electron transfer events
between the catalysts and organic substrates.[1] These reactions
frequently occur at mild temperatures, including room temperature, using
visible light sources such as LEDs that provide intense light with narrow
wavelength emissions. As such, materials for conducting photoredox chemistry at
the lab scale are readily available for chemists and engineers. However,
significant challenges remain in visible-light photoredox catalysis. The
primary challenge in industrial applications is scaling up photoredox reactions
from laboratory scale batch reactors to reactors that are capable of
multi-kilogram scale production. Proper reactor design relies on rigorous
understanding of the inherent kinetics of photoredox reactions, which are
largely unexplored. The photon flux, the overall observed rate at which photons
are received in the reactor, must be high enough to ensure that the inherent
kinetics of the reaction are the operating conditions of the reactor. The
lamp-reactor geometry, therefore, is a critical design factor in scalable
photoredox flow chemistry. Maximizing the photon flux also likely depends on
careful tuning of the catalyst concentration, reactant concentration, and light
intensity. Continuous
flow reactors can facilitate improved photon fluxes and increased throughput
through significantly decreased reaction times compared to batch reactions,
which are both necessary for industrial photoredox catalysis.[2] Flexible
fluoropolymer tubing is chemically resistant to many materials and highly
transparent to visible light, meaning that tubing can be wrapped around light
sources such as LEDs for access to customizable tubular flow reactors for
photoredox applications. The short tube diameters allow for shorter path
lengths, meaning that photons are more evenly distributed throughout the
reactor, increasing the apparent rate of reaction. However, general principles
and heuristics for designing such flow reactors are not yet available to
process chemists and engineers. This work establishes heuristics for employing
flow reactors in photoredox chemistry. The effects of reactant and catalyst
concentration, tube diameter, and LED intensity on the observed photon fluxes
and rates of reaction will be discussed. The model reaction for establishing
the heuristics will be the oxidation of 9,10-diphenylanthracene using molecular
oxygen and a common ruthenium photoredox catalyst, Ru(bpy)3Cl2.
The quantum yield for this reaction is known,[3] meaning that the
photon flux under a given set of reaction conditions can be calculated directly
once the rate of reaction is measured. These heuristics will then be examined
against a pyrazole synthesis driven by photoredox catalysis, using the same
ruthenium catalyst, to see if heuristics accurately predict how the observed
rates of reaction change with changes in reaction conditions in flow. References
[1] C. K.
Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev. 2013, 113,
5322-5363.
[2] Y.
Su, N. J. W. Straathof, V. Hessel, T. Noel, Chem. Eur. J. 2014, 20,
10562-10589.
[3] S. P.
Pitre, C. D. McTiernan, W. Vine, R. DiPucchio, M. Grenier, J. C. Scaiano, Sci.
Rep. 2015, 5, 16397.
abstract presentation was sponsored by AbbVie. AbbVie contributed to the
design, research, and interpretation of data, writing, reviewing, and approving
the publication. All authors are AbbVie employees.