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Bioreactor, a device which controls a biologically active environment.

Chemical reactor, a device for containing and controlling a chemical reaction

Fusion reactor, a device for containing and controlling a fusion power reaction

An inductor (possessing reactance) in an electrical power grid

A current limiting reactor is used to limit starting current of motors and to protect variable frequency drives

Nuclear reactor, a device for containing and controlling a nuclear reaction

Reactor (software), a physics simulation engine

The reactor pattern, a design pattern used in concurrent programming

In entertainment

Reactor an alternative title for the 1978 Italian film War of the Robots directed by Alfonso Brescia

Re·ac·tor, a 1981 album by Neil Young and Crazy Horse

Reactor (arcade game), an arcade game created by Gottlieb

Reactor, Inc., a defunct interactive entertainment company founded by Mike Saenz

Reactor, a comedy series on Syfy, hosted by David Huntsberger.

The Reactor (show rod), a show car built by Gene Winfield

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Chemical reactor

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A chemical reactor is an enclosed volume in which a chemical reaction takes place.[1][2][3][4] In chemical engineering, it is generally understood to be a process vessel used to carry out a chemical reaction,[5] which is one of the classic unit operations in chemical process analysis. The design of a chemical reactor deals with multiple aspects of chemical engineering. Chemical engineers design reactors to maximize net present value for the given reaction. Designers ensure that the reaction proceeds with the highest efficiency towards the desired output product, producing the highest yield of product while requiring the least amount of money to purchase and operate. Normal operating expenses include energy input, energy removal, raw material costs, labor, etc. Energy changes can come in the form of heating or cooling, pumping to increase pressure, frictional pressure loss or agitation.

Chemical reaction engineering is the branch of chemical engineering which deals with chemical reactors and their design, especially by application of chemical kinetics to industrial systems.

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A chemical reactor is an enclosed volume in which a chemical reaction takes place.[1][2][3][4] In chemical engineering, it is generally understood to be a process vessel used to carry out a chemical reaction,[5] which is one of the classic unit operations in chemical process analysis. The design of a chemical reactor deals with multiple aspects of chemical engineering. Chemical engineers design reactors to maximize net present value for the given reaction. Designers ensure that the reaction proceeds with the highest efficiency towards the desired output product, producing the highest yield of product while requiring the least amount of money to purchase and operate. Normal operating expenses include energy input, energy removal, raw material costs, labor, etc. Energy changes can come in the form of heating or cooling, pumping to increase pressure, frictional pressure loss or agitation.

Chemical reaction engineering is the branch of chemical engineering which deals with chemical reactors and their design, especially by application of chemical kinetics to industrial systems.

The innovative chemical synthesis reactors, EasyMax and OptiMax, are easy-to-use platforms that accurately and precisely control reaction parameters and execute recipes, thus enabling every chemist to perform reactions reproducibly. Experiment procedures can be run unattended, around the clock, all data is automatically recorded, and ready to be instantly shared and reported. Chemical reactors reinvent the way scientists work, enabling their ability to generate more information per experiment, and accelerate the delivery of life-changing products. Automated chemical synthesis reactors are well established in chemical and pharmaceutical industry, and are essential to speed up time-to-market cycles at lower R&D costs. 

Organic Chemistry Portal

Reactions >> Special Topics

Flow Chemistry

Dr Claudio Battilocchio and Prof Steven V. Ley (Innovative Technology Centre, University of Cambridge, United Kingdom)

Introduction

The concept of "flow chemistry" defines a very general range of chemical processes that occur in a continuous flowing stream, conventionally taking place in a reactor zone. The application of flow chemistry relies on the concept of pumping reagents using many reactors types to perform specific reactions. The most common types of reactors are plug flow reactors and column reactors, whilst for specific chemistries more sophisticated reactor designs might be needed (e.g., photoreactors, electrochemical reactors, etc).

Flow Chemistry: Set-Up, Advantages and Parameters

System set-up

Shown below is a general schematic representation for a flow chemistry set-up (see Darvas F., Dorman G., Hessel V. Flow Chemistry, Volume 1: Fundamentals).

a) Pumps: used to deliver reproducible quantities of solvents and reagents; the usual types are piston, peristaltic, syringe or gear centrifugal pumps

b) Reaction loops: used to introduce small volumes of reagents

c) T-piece: primary mixing point, where reagents streams are combined

d) Coil reactor: provides residence time for the reaction

e) Column reactor: packed with solid reagents, catalysts or scavengers

f) Back pressure regulator: controls the pressure of the system

g) Downstream unit: in-line analytics, work-up operations, etc.

Figure 1. Examples of commercially available flow systems

Advantages of flow chemistry

There are well-defined key advantages using flow technologies as compared to standard batch chemistry methods:

Improved heat transfer

Improved mass transfer/mixing

Reproducibility

Scale-up

Extreme reaction conditions (high/low temperature, high pressure)

Multistep (telescoping)

In-line downstream processing

Automation

Improved Safety (managing hazardous reagents and intermediates)

Parameters in flow chemistry

Beyond the aforementioned advantages, running a reaction under flow conditions requires knowledge of many reaction parameters (e.g. stoichiometry, reaction time, concept of steady state, etc).

a) Stoichiometry

Whilst under batch conditions the stoichiometry is set by the molar ratio of the reagents used, in a flow process the ratio of parameters such as flow rate and molarity is used to set the specific stoichiometry.

b) Residence time as "reaction time"

In batch mode synthesis the reaction time is determined by the time a vessel is stirred under fixed conditions, whereas the concept of reaction time in a flow process is expressed by the residence time, i.e., the time reagents spend in the reactor zone. Residence time is given by the ratio of the reactor volume and the reaction flow rate (overall flow rate).

τ = V/q

where τ is the variable corresponding to the residence time, V is the volume of the system, and q is the flow rate for the system

c) Flow rates

While in batch mode, the reaction kinetics are controlled essentially by the reagent exposure time under the specified reactions conditions, under flow conditions reactions kinetics are controlled by the flow rates of the reagents streams. The flow rates of the reagents indeed will influence the residence time of the reaction and have an impact on the outcome of the transformation.

q = dV/dt

q is usually expressed in units such as mL min-1

d) Volume vs space (steady state)

When considering a batch reaction, the reagent and product concentrations vary over the time, and mixing becomes a relevant aspect (especially when increasing the scale of the reaction) in order to reduce concentration gradients that affect the kinetics of a reaction. Under flow conditions, each portion of the reactor is defined by specific concentrations of the starting material(s) and product(s): in this sense, the reaction profile within a flow reactor can be defined within space rather than time. A very important parameter in flow chemistry is the steady state that defines a condition where all the parameters are defined and remain unchanged (steady) at a particular point in time.

e) Mixing and mass transfer

Mixing in a flow process is highly advantageous, compared to batch mode, as it is determined by diffusion within very small volumes of reagents. A high degree of mixing translates into better reaction profiles. Under flow conditions, indeed, mass transfer is considered very effective and determines the specific and enhanced kinetics observed. There are specific aspects of mixing that should be considered (e.g. axial vs. vortex mixing) and are dependent on specific fluid behaviours, namely plug or laminar flow patterns.

e) Temperature control and heat transfer

The control of temperature in flow processes can be achieved very accurately, due to the high surface area-to-volume ratio.

Accordingly, heat transfer can be very efficient although this parameter depends on the specific aforementioned aspects of the fluid behaviour. Indeed, depending on whether the flow is laminar or turbulent, heat transfer can follow different patterns.

Standard Types of Flow Reactors

a) Plug flow reactors

This type of reactor has cylindrical geometry (e.g. coil reactors). Examples of plug flow reactors can be found in the literature.

See: Org. Lett., 2015, 17, 3218-3221 (Ley et al.); Org. Biomol. Chem. 2014, 12, 3611-3615 (Kirschning et al.); Angew. Chem. Int. Ed. 2015, 54, 678-682 (Seeberger et al.); Angew. Chem. Int. Ed., 2013, 52, 11628-11631 (Buchwald et al.); Synlett 2016, 27, 159-163 (Baxendale et al.)

A specific example of the miniaturized plug flow reactor is described by the group of Prof Yoshida, who have implemented the concept of flash chemistry, whereby the transformations are run within seconds (for example, see: Angew. Chem. Int. Ed. 2015, 54, 1914-1918)

b) Column reactors

Column reactors can be packed with specific materials that can either act as catalysts or stoichiometric reagents. In either case, there are important implications for the downstream processing operations. Examples of column reactors can be found in the literature.

See: Angew. Chem. Int. Ed., 2014, 54, 263-266 (Buchwald et al.); Chem. Sci. 2015, 6, 1120-1125 (Ley et al.); Nature, 2015, 520, 329-332 (Kobayashi et al.); Nature Chemistry, 2016, DOI: 10.1038/nchem.2439 (Battilocchio et al.)

c) Gas reactors

Using gases as reagents can represent several challenges in batch mode. Scientists have realised several gas flow reactor designs that reduce the issues of dealing with gases, increasing the process efficiency and robustness under flow conditions. Examples of gas reactors can be found in the literature.

See: Org. Lett. 2010, 12, 1596-1598 (Ley et al.); Angew. Chem. Int. Ed., 2012, 51, 1706 -1709 (Seeberger et al.); Org. Lett., 2013, 15, 5590-5593 (Kappe et al.)

Particularly interesting is the case of the tube-in-tube, which was invented by the group of Prof Steven Ley (Acc. Chem. Res., 2015, 48, 349-362) and used for a myriad of gases.

d) Reactors for slurries

Reactions can form slurries and these can represent a real challenge, especially from the perspectives of micro- and meso-fluidics. Chemists have come up with a solution to overcome these issues, in order to process slurries continuously. Examples of reactors for slurries can be found in the literature.

See: Chem. Eng. Technol. 2015, 38, 259-264 (Ley et al.)

e) Photochemical flow reactors

Flow photochemical reactors have revolutionised the way chemists deal with this area of chemistry. These systems can be very easy to set up and use, and allow chemists to manage either small- or large-scale reactions without any major challenges. Examples of photochemical flow reactors can be found in the literature.

See: React. Chem. Eng., 2016, DOI: 10.1039/C5RE00037H (Baxendale et al.); React. Chem. Eng., 2016, 1, 73-81 (Noel et al); Angew. Chem. Int. Ed. 2013, 52, 1499 -1502 (Booker-Milburn et al.); Green Chem., 2013, 15, 177-180 (Poliakoff et al.)

f) Trickle bed reactors (TBRs)

Trickle bed reactors represent a powerful system to run triphasic processes under flow conditions. The fixed bed is usually packed with a catalyst (solid) and the system can be run using various gas and liquid feeds.

Examples of trickle bed reactors can be found in the literature.

See: Org. Process Res. Dev., 2014, 18, 1560-1566 (Ley et al.); ACS SusChemEng, DOI: 10.1021/acssuschemeng.6b00287 (Battilocchio et al);

Recent Literature

Display all abstracts

A continuous flow process converts isoxazoles into their oxazole counterparts via a photochemical transposition reaction. A series of di- and trisubstituted oxazoles were realized through this rapid and mild flow process.

C. Bracken, M. Baumann, J. Org. Chem., 2020, 85, 2607-2617.

A selective acylation of readily accessible organomagnesium reagents with commercially available esters proceeds in short residence times in continuous flow. Flow conditions prevent premature collapse of the hemiacetal intermediates despite noncryogenic conditions, thus furnishing ketones in good yields.

B. Heinz, D. Djukanovic, M. A. Ganiek, B. Martin, B. Schenkel, P. Knochel, Org. Lett., 2020, 22, 493-496.

The use of copper tubings enables a simple continuous flow synthesis of alkenyl chlorides in very good yields from the corresponding readily available alkenyl iodides with full retention of the double bond geometry. The reaction time was reduced 24 to 48fold compared to the batch process.

A. Nitelet, V. Kairouz, H. Lebel, A. B. Charette, G. Evano, Synthesis, 2019, 51, 251-257.

A continuous flow method for the selective reduction of aromatic nitriles to the corresponding primary amines is based on a ruthenium-catalysed transfer-hydrogenation process with isopropanol as both solvent and reducing agent.

R. Labes, D. González-Calderón, C. Battilocchio, C. Mateos, G. R. Cumming, O. de Frutos, J. A. Rincón, S. V. Ley, Synlett, 2017, 28, 2855-2858.

A scalable, photocatalytic coupling of silicon amine protocol (SLAP) reagents and aldehydes provides substituted morpholines, oxazepanes, thiomorpholines, and thiazepanes under continuous flow conditions in the presence of an inexpensive organic photocatalyst (TPP) and a Lewis acid additive.