1. Session 2: Flow Chemistry
Chris Rayner

2. Flow Chemistry within iPRD
Presentation focuses on:
Track record/in house expertise (highlights)
Current projects
Future perspectives/targets
Discussion welcomed on:
Comments/suggestions on project portfolio
Identification of interested partners/ consortia for collaboration, application or information exchange

3. Flow Chemistry within iPRD
Continuous Synthetic Chemistry
Thermolytic reactions
Hazardous reagents
Photochemistry
Equipment and modelling
Rotating tube and spinning disc reactors
Reactor and Reaction Modelling
Microchannel reactors
In-process analytics
Supercritical fluids
Continuous reactions and product isolation

4. Thermolytic reactions in flow (Steve Marsden)
Flow Chemistry
Thermolytic reactions in flow (Steve Marsden)
Pressurised flow reactors allow reactions to be carried out at temperatures above normal boiling point of solvent
Short residence time in high temperature zone reactors for high activation energy reactions
Example: thermolytic elimination of CO2 from b-lactones – reduced waste synthesis of alkenes

5. Thermolytic reactions in flow (Steve Marsden)
Flow Chemistry
Thermolytic reactions in flow (Steve Marsden)
Controlled residence, high temperature zone reactors for high activation energy reactions
Example: controlled thermolytic generation of reactive heterocumulenes for de novo heteroaromatic synthesis ([4+2] cycloaddition followed by elimination)

6. Hazardous reactions (Rob Hammond)
Flow Chemistry
Hazardous reactions (Rob Hammond)
Use of hazardous reagents particularly problematic in large scale batch processes
Azide and cyanide widely used in synthetic chemistry for heterocycle synthesis, introduction of N-functionality, C-1 synthon etc.
Flow techniques required
Hazardous scale-up, particularly if require parent acids which are highly toxic, volatile and potentially explosive
Use of flow reactor to generate HCN or HN3 in small quantities under highly controlled conditions
Objective is to maximise safety and efficiency aspects in flow reactor
Long term goal is to develop a reaction system that can allow large scale synthesis of intermediates using hazardous reagents

7. Continuous synthetic photochemistry (Chris Rayner)
Flow Chemistry
Continuous synthetic photochemistry (Chris Rayner)
Synthetic photochemistry offers opportunities to access functionality otherwise very difficult to obtain.
Often limited by poor yields and prolonged reaction times.
Continuous reaction approach greatly increases yields and rates
Lower power lamps
Reduced decomposition
Shorter reaction times
Higher conversions

8. Continuous synthetic photochemistry (Chris Rayner)
Flow Chemistry
Continuous synthetic photochemistry (Chris Rayner)
Photo-Fries rearrangement – very versatile, but usually limited to ca. 40% conversion.
Product build up inhibits further reaction (more intense absorption)
Currently investigating biphasic approaches where product is selectively extracted as it is formed
Dramatic increase in conversions, yield and rates.

9. New continuous reactors (Chris Rayner/Roshan Jachuck)
Flow Chemistry
New continuous reactors (Chris Rayner/Roshan Jachuck)
Opportunity for new reactor designs
Rotating tube reactors (Roshan Jachuck, Clarkson, NY)
Residence time of seconds to several minutes (or batch)
Highly sheered films ( microns)
Immiscible liquids of different densities (e.g. water/organic) form 2 independent micron scale layers
Ideal for biphasic photochemistry and other two phase reactions
Not prone to blocking; also good for reactions involving gases

10. Reaction modelling (Annette Taylor)
Flow Chemistry
Reaction modelling (Annette Taylor)
Fundamental kinetic and thermodynamic analysis of reaction processes in complex systems (practical and theoretical)
Modelling of features generic to any reaction containing feedback through autocatalysis or heat (thermal runaway)
Examples of feedback in organic chemistry include:
Addition of dialkylzinc reagents to pyrimidinecarbaldehyde (the Soai reaction)
Formaldehyde-sulfite addition
Polymerisations (e.g. vinyl acetate)
Continuous photochemistry (e.g. [2+2] cycloadditions)
Mechanistic studies on CO2 capture and release (CCS)

11. Reaction modelling (Annette Taylor)
Flow Chemistry
Reaction modelling (Annette Taylor)
Chemical flow systems
EPSRC funded project in collaboration with Mark Wilson & Melanie Britton (Birmingham)
Chemical reactions in plug-flow / packed-bed / Taylor-Couette flow
Influence of flow on chemical amplification (autocatalysis); chemical waves (spatial concentration profiles)
Reaction-diffusion-advection simulations
2d and 3d imaging of a chemical wave
Dispersion in a packed bed
Simulated wave profiles
Taylor, A.F.; Britton M.M. Chaos , pp , 2006 , 16.
Britton, M.M.; Sederman, A.J.; Taylor, A.F.; Scott S.K.; Gladden, L.F., Journal of Physical Chemistry A , pp , 2005 , 109.

12. Flow Chemistry Microfluidics (Nik Kapur and Mark Wilson)
Micromixing for reaction:
The aim here was to use computational methods to develop a mixing device for a specific set of flow conditions. The device is currently being manufactured.
Mixing by chaotic advection:
This was a study of a small geometry where oscillation of the free surface (one roll speed is perturbed) causes mixing of the fluid. Shown on the movie are small tracer particles within the flow illustrating the mixing. The experiments on the left provide validation.
Ambient fluid capture:
The following slide shows how, using the control of eddies within flow, particles or reagents can be trapped.
Autocatalytic reaction:
This slide illustrates a simple autocatalytic scheme within the same geometry. Its possible to build a series of reactions into these models to couple flow and kinetics.
2 Phase droplet:
An illustration of a 2-phase simulation similar to that found within a microemulsion device. This sort of method can be used to optimise geometric and flow conditions for robust droplet formation. The group also has considerable experience in experiments in this area (2-phase flow).

13. Microfluidics (Nik Kapur and Mark Wilson)
Flow Chemistry
Microfluidics (Nik Kapur and Mark Wilson)
For a particular oscillatory reaction, needed:
Rapid mixing
Uniform concentration profile
Long residence time, but
No stagnant regions
The aim here was to use computational methods to develop a mixing device for a specific set of flow conditions. The device is currently being manufactured.

14. Flow Chemistry Micromixing for reaction:
The aim here was to use computational methods to develop a mixing device for a specific set of flow conditions. The device is currently being manufactured.
Mixing by chaotic advection:
This was a study of a small geometry where oscillation of the free surface (one roll speed is perturbed) causes mixing of the fluid. Shown on the movie are small tracer particles within the flow illustrating the mixing. The experiments on the left provide validation.
Ambient fluid capture:
The following slide shows how, using the control of eddies within flow, particles or reagents can be trapped.
Autocatalytic reaction:
This slide illustrates a simple autocatalytic scheme within the same geometry. Its possible to build a series of reactions into these models to couple flow and kinetics.
2 Phase droplet:
An illustration of a 2-phase simulation similar to that found within a microemulsion device. This sort of method can be used to optimise geometric and flow conditions for robust droplet formation. The group also has considerable experience in experiments in this area (2-phase flow).

15. Mixing by chaotic advection
Flow Chemistry
Mixing by chaotic advection
Finite element simulation
Experimental
This was a study of a small geometry where oscillation of the free surface (one roll speed is perturbed) causes mixing of the fluid. Shown on the movie are small tracer particles within the flow illustrating the mixing. The experiments on the left provide validation.

16. Flow Chemistry Micromixing for reaction:
The aim here was to use computational methods to develop a mixing device for a specific set of flow conditions. The device is currently being manufactured.
Mixing by chaotic advection:
This was a study of a small geometry where oscillation of the free surface (one roll speed is perturbed) causes mixing of the fluid. Shown on the movie are small tracer particles within the flow illustrating the mixing. The experiments on the left provide validation.
Ambient fluid capture:
The following slide shows how, using the control of eddies within flow, particles or reagents can be trapped.
Autocatalytic reaction:
This slide illustrates a simple autocatalytic scheme within the same geometry. Its possible to build a series of reactions into these models to couple flow and kinetics.
2 Phase droplet:
An illustration of a 2-phase simulation similar to that found within a microemulsion device. This sort of method can be used to optimise geometric and flow conditions for robust droplet formation. The group also has considerable experience in experiments in this area (2-phase flow).

17. Ambient field capture – controlling delivery of reagents?
Flow Chemistry
Ambient field capture – controlling delivery of reagents?
The following slide shows how, using the control of eddies within flow, particles or reagents can be trapped.

18. Flow Chemistry Micromixing for reaction:
The aim here was to use computational methods to develop a mixing device for a specific set of flow conditions. The device is currently being manufactured.
Mixing by chaotic advection:
This was a study of a small geometry where oscillation of the free surface (one roll speed is perturbed) causes mixing of the fluid. Shown on the movie are small tracer particles within the flow illustrating the mixing. The experiments on the left provide validation.
Ambient fluid capture:
The following slide shows how, using the control of eddies within flow, particles or reagents can be trapped.
Autocatalytic reaction:
This slide illustrates a simple autocatalytic scheme within the same geometry. Its possible to build a series of reactions into these models to couple flow and kinetics.
2 Phase droplet:
An illustration of a 2-phase simulation similar to that found within a microemulsion device. This sort of method can be used to optimise geometric and flow conditions for robust droplet formation. The group also has considerable experience in experiments in this area (2-phase flow).

19. Autocatalytic reactions
Flow Chemistry
Autocatalytic reactions
For reaction
R+B→2B
This slide illustrates a simple autocatalytic scheme within the same geometry. Its possible to build a series of reactions into these models to couple flow and kinetics.

20. Flow Chemistry Micromixing for reaction:
The aim here was to use computational methods to develop a mixing device for a specific set of flow conditions. The device is currently being manufactured.
Mixing by chaotic advection:
This was a study of a small geometry where oscillation of the free surface (one roll speed is perturbed) causes mixing of the fluid. Shown on the movie are small tracer particles within the flow illustrating the mixing. The experiments on the left provide validation.
Ambient fluid capture:
The following slide shows how, using the control of eddies within flow, particles or reagents can be trapped.
Autocatalytic reaction:
This slide illustrates a simple autocatalytic scheme within the same geometry. Its possible to build a series of reactions into these models to couple flow and kinetics.
2 Phase droplet:
An illustration of a 2-phase simulation similar to that found within a microemulsion device. This sort of method can be used to optimise geometric and flow conditions for robust droplet formation. The group also has considerable experience in experiments in this area (2-phase flow).

21. 2-Phase droplet simulation
Flow Chemistry
2-Phase droplet simulation
An illustration of a 2-phase simulation similar to that found within a microemulsion device. This sort of method can be used to optimise geometric and flow conditions for robust droplet formation. The group also has considerable experience in experiments in this area (2-phase flow).

22. P1 R H C F P2 B Continuous Process for Hydrothermal
Synthesis of Photocatalytic Nanomaterials
University of Leeds Prof XZ Wang
University College London, Dr J Darr
Process Scale-up: PAT and Multi-scale Modeling
PID P1 P2 H R C F B
H2O
Several metal
salts in solution
Solar energy
Photocatalysts
Hydrogen
Oxygen
Water
Hydrothermal
synthesis
TiO2 ZnO SnO2 …
Nano size < 100 nm
SCW
Metal
feed
AUX
Feed
> £2 million

23. Reactor Design for Solvent Free Synthesis of Nanomaterials
Feed S2
Product S5
Feed S1
Inert gas
fixed bed: no;
fluidised bed: yes R1 R2
Feed S4
Feed S2
Product S3
Feed S1
Inert gas S3 R2 R1 or
Product S5
Feed S4
Jet-mixed tank R2
Impinging-jet R2
Feed S1
Feed S2
Inert gas
fixed bed: no;
fluidised bed: yes
Product S3
Packed
bed
Minimum
fluidisation
Gas
Fluidised
Filter

24. scCO2 Flow Chemistry (Chris Rayner)
Extensive expertise in reactions in sCO2
Unique solvent, inexpensive, easy disposal and no solvent residues
Mostly done in batch in Leeds
Excellent understanding of likely problems (solubility, reactivity, high pressure)
scCO2 (or liquid CO2) flow methods in reactions, product isolation and purification.
E.g. stripping and/or recycling of dipolar aprotic solvents (DMF)
Crystallisation and drying

25. SCW Oxidation of Organics (Paul Williams)
Flow Chemistry
SCW Oxidation of Organics (Paul Williams)
Supercritical water oxidation very efficient for destruction of organics (Tc 374 ºC, Pc 221 bar)
Extensive experience in supercritical water technology (mainly batch)
Continuous SCW system to be commissioned shortly (Mojtaba Ghadiri/Yulong Ding)
Current projects include
SCW oxidation of organic wastes
SCW gasification of food wastes

26. Continuous reactions and purification (iPRD)
Flow Chemistry
Continuous reactions and purification (iPRD)
Coupling reaction chemistry to product purification
Batch or continuous reactions
Batch or continuous purification methods (e.g. crystallisation)
Interdependence of purification and reaction chemistry
Improve reproducibility and quality of process and product
Extensive experience is all relevant areas

27. Points for discussion Comments and suggestions on project portfolio
Flow Chemistry
Points for discussion
Comments and suggestions on project portfolio
Identification of interested partners to form consortia for collaboration, application or information exchange