Session 2: Flow ChemistryChris Rayner

Flow Chemistry within iPRD

Presentation focuses on:Track record/in house expertise (highlights)Current projectsFuture perspectives/targets

Discussion welcomed on:Comments/suggestions on project portfolioIdentification of interested partners/ consortia for collaboration, application or information exchange

Flow Chemistry

Flow Chemistry within iPRDContinuous Synthetic Chemistry

Thermolytic reactionsHazardous reagentsPhotochemistry

Equipment and modellingRotating tube and spinning disc reactorsReactor and Reaction ModellingMicrochannel reactors

In-process analytics

Supercritical fluids

Continuous reactions and product isolation

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 β-lactones –reduced waste synthesis of alkenes

R1 H

O

R2

O

X+O

O

R1 R2- CO2

R1 R2high temp.

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)

O

O

R1

NHR3 O

OtBuO

NR3

R1

R1

O O

OtBu

150-200oC

R2

OO

R1

R2

O

R3N

R2

R1150-200oC

R2 R2

R1

R2

OEt

OEt

Flow Chemistry

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

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 lampsReduced decompositionShorter reaction timesHigher conversions

Flow Chemistry

+

O

O

hν

OOO

O

Ethanol81% 89 %

Batch, 2hContinuous, 15min

Continuous, 2h, >95%

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 formedDramatic increase in conversions, yield and rates.

hνO

O

OH

OHO

O

Batch 125W, 12h, hexane/aq. K2CO3 (10:1), >95%

Batch 400W, 56h, MeCN, 10%Continuous 400W, 80h, MeCN, 54%, 3:2

+

3 : 2

Flow Chemistry

Pump

Lamp

Tubingaround lamp

Hexane + substrateAq. K2CO3 + product

New continuous reactors (Chris Rayner/Roshan Jachuck)Opportunity for new reactor designsRotating tube reactors (Roshan Jachuck, Clarkson, NY)Residence time of seconds to several minutes (or batch)Highly sheered films (100-200 microns)Immiscible liquids of different densities (e.g. water/organic) form 2 independent micron scale layersIdeal for biphasic photochemistry and other two phase reactionsNot prone to blocking; also good for reactions involving gases

Flow Chemistry

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 additionPolymerisations (e.g. vinyl acetate)

Continuous photochemistry (e.g. [2+2] cycloadditions)Mechanistic studies on CO2 capture and release (CCS)

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

Dispersion in a packed bed2d and 3d imaging of a chemical waveSimulated wave profiles

Taylor, A.F.; Britton M.M. Chaos , pp.037103 , 2006 , 16.Britton, M.M.; Sederman, A.J.; Taylor, A.F.; Scott S.K.; Gladden, L.F., Journal of Physical Chemistry A , pp.8306-8313 , 2005 , 109.

Flow Chemistry

Reaction modelling (Annette Taylor)

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).

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

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).

Flow Chemistry

Experimental

Finite element simulation

Flow Chemistry

Mixing by chaotic advection

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).

Flow Chemistry

Flow Chemistry

Ambient field capture – controlling delivery of reagents?

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).

Flow Chemistry

For reactionR+B→2B

Flow Chemistry

Autocatalytic reactions

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).

Flow Chemistry

Flow Chemistry

2-Phase droplet simulation

PID

P1

P2

H R CFB

H2O

Several metal salts in solution

University College London, Dr J Darr

University of Leeds Prof XZ Wang

Water Water Solar energySolar energy

PhotocatalystsPhotocatalystsHydrogenHydrogenOxygenOxygen

TiOTiO2 2 ZnOZnO SnOSnO2 2 ……

Nano size < 100 nmNano size < 100 nm

Hydrothermal Hydrothermal synthesissynthesis

SCWSCW MetalMetalfeedfeed

AUX AUX FeedFeed

> > ££2 million 2 million

ContinuousContinuous Process for Hydrothermal Process for Hydrothermal Synthesis of Synthesis of PhotocatalyticPhotocatalyticNanomaterialsNanomaterials

Process ScaleProcess Scale--up: PAT and Multiup: PAT and Multi--scale Modelingscale Modeling

Feed S2

Product S5

Feed S1

Inert gasfixed bed: no;fluidised bed: yes

R1

R2

Feed S4

Feed S2

Product S3

Feed S1

Inert gas

S3

R2

R1 or Product S5

Product S5

Feed S4

Feed S4S3

R2

Jet-mixed tank R2

Impinging-jet R2

Feed S1

Feed S2

Inert gasfixed bed: no;fluidised bed: yes Product S3

Packed bed

Minimumfluidisation

Gas

Fluidisedbed

Gas

Filter

O

O

HO

NH2

HO

O

O

NH2

HO

O

HOO

O

N

O

O

CH 3I

glycol chitosan

x

y

n

O

O

NH2

HO

O

HO

O

O

HON

O

HO

quaternary ammonium palmitoyl glycol chitosan (GCPQ)

u v

O

O

HO

N

O

HO

O

O

NH2

HO

O

HO

CH3

HO

O

CH3

H3CN

O

HOO

O

+w

Feed S2Palmitic acid N-hydroxysuccinimide

Reactor R1 Reactor R2Product S5

Mixture of glycol chitosan (GC), sodium bicarbonate dissolved in water Feed S1

S3: Palmitoyl glycol chiltosan; unreacted GC,water,sodiumbicarbonate

S4: Methyl iodide, sodium hydroxide & sodium iodide in water, or betaine, sodium bicarbonate, water, N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

S3

Feed S4

Feed S2Palmitic acid N-hydroxysuccinimide

Reactor R1 Reactor R2Product S5

Mixture of glycol chitosan (GC), sodium bicarbonate dissolved in water Feed S1

S3: Palmitoyl glycol chiltosan; unreacted GC,water,sodiumbicarbonate

S4: Methyl iodide, sodium hydroxide & sodium iodide in water, or betaine, sodium bicarbonate, water, N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

S3

Feed S4

Reactor Design for Solvent Free Synthesis of Reactor Design for Solvent Free Synthesis of NanomaterialsNanomaterials

scCO2 Flow Chemistry (Chris Rayner)Extensive expertise in reactions in sCO2Unique solvent, inexpensive, easy disposal and no solvent residuesMostly done in batch in LeedsExcellent 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

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 wastesSCW gasification of food wastes

Flow Chemistry

Continuous reactions and purification (iPRD)

Coupling reaction chemistry to product purificationBatch or continuous reactions Batch or continuous purification methods (e.g. crystallisation)Interdependence of purification and reaction chemistryImprove reproducibility and quality of process and productExtensive experience is all relevant areas

Flow Chemistry

Points for discussion

Comments and suggestions on project portfolio

Identification of interested partners to form consortia for collaboration, application or information exchange

Flow Chemistry