Applications

The application of continuous flow micro reactors is based on solving problems that are currently observed in the batch technology being used for the synthesis of chemical products in the fine chemical and pharmaceutical industry. The following advantages can be expected when using a continuous flow micro reactor in place of a conventional batch reactor:

• Safe use of more extreme reaction conditions (even for dangerous reactions);

• Highly exothermic reactions

• Thermally unstable compounds or mixtures

• Highly reactive compounds

• High potentcy compounds

• Increased selectivity of reactions; a reduction in the use of raw materials and energy with reduced waste

production

• Decrease in development time; a shorter experiment time, no need for scale-up

• Reduction in product lead time; combination of more synthetic steps in a single micro reactor

APPLICATION NOTES / WHITEPAPERS

2012

Presentation: A Flexible Flow Platform for Rapid Reaction Screening and Process Scale-up Charlotte Wiles \| 2011-10-25	Download
The Scale-up of (Z)-Ethyl-2-cyano-3-phenylacrylate Synthesis-From Labtrix-S1 Parameter Screening to KiloFlow Production Dr. Charlotte Wiles, \| 2012, 01-25	Download

2011

Use of a commercially available device for the evaluation of heterogeneous reagents, catalysts and scavengers under continuous flow conditions Dr. Charlotte Wiles \| 2011, 09-01	Download
Translation of microwave methodology to continuous flow for the synthesis of diaryl esthers via an SNAr reaction Dr. Charlotte Wiles, \| 2011, 06-08	Download
Rapid extraction of kinetic information using micro reactor technology Dr. Charlotte Wiles, Dr. Bongkot Ngamsom \| 2011, 05-08	Download
The use of micro reactors for the extraction of kinetic information from synthetic reactions and application to the Paal-Knorr pyrrole synthesis. Dr. Charlotte Wiles, Dr. Bongkot Ngamson, Dr. Charl Stemmet \| 2011 01-24	Download
A safe and efficient method for the preparation of organic azides under continuous flow. Dr. Charlotte Wiles \| 2011, 01-10	Download

2010

Biphasic PNA hydrolysis Dr. Charlotte Wiles, Dr Bongkot Ngamsom \| 2010, 12-13	Download
Continuous flow synthesis of β-Peptides within labtrix® reactors Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010, 12-13	Download
High-throughput synthesis of alkyl amides within labtrix reactors Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010, 11-01	Download
Continuous flow transfer hydrogenations Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010,10-20	Download
Manipulation of Grignard reagents within labtrix reactors Dr. Charlotte Wiles \| 2010, 20-09	Download
Knoevenagel condensation Dr. Charlotte Wiles \| 2010-08-23	Download
Ester hydrolyses Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010-07-30	Download
Continuous flow esterifications Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010-07-26	Download
The use of static micro mixers within labtrix® micro reactors Dr. Charlotte Wiles \| 2010, 06-07	Download
Scale out of chemical synthesis in flow reactors Dr. P.Watts \| 2010, 07-01	Download
The scale-up of chemical sythesis using micro reactors C.Wiles and P.Watts \| Chemistry Today, 2010, 4-6

2009

Continues flow organic synthesis: a tool for the modern medicinal chemist C. Wiles & P.Watts \| Future Medicinal Chemistry, 2009, 1(9), 1593-1612
The use of micro reactors as tools for the high-throughput synthesis of small organic molecule libraries C. Wiles \| Speciality Chemicals Magazine, 2009, 29(7), 40-41
A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme A. M. Hickey, B. Ngamsom, C. Wiles, G. M. Greenway, P. Watts and J. A. Littl \| Biotechnology J., 2009, 4(4), 510-516.
The development and evaluation of a continuous flow process for the lipase-mediated oxidation of alkenes C. Wiles, M. J. Hammond and P. Watts \| Belstein Journal Organic Chemistry, 2009
Enhanced chemical synthesis in flow reactors C.Wiles and P.Watts \| Chimica Oggi, 2009, 27, 3, 34-36.

2008

Evaluation of the heterogeneously catalysed strecker reaction conducted under continuous flow C. Wiles and P. Watts \| EurJOC, 2008, 5597-5613. DOI: 10.1002/ejoc.200800751.
Deuterated isotope labelling of phenol derivatives within micro reactors J. Hooper, P. Watts and C. Wiles \| Microfluidics and Nanofluidics, 2008, 5, 595-602. DOI 10.1007/s10404-008-0274-8.
An integrated microreactor for the multicomponent synthesis of α-aminonitriles C. Wiles and P. Watts \| Org. Proc. Res. Dev., C. Wiles* and P. Watts, 2008, 12, 1001-1006. DOI: 10.1021/op800025p.

2007

An efficient, chemoselective technique for the continuous flow synthesis of thioacetals C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron Lett., 2007, 48, 7362-7365. DOI: 10.1016/j.tetlet.2007.08.027.
An expedient, scalable synthesis of the natural product L-anserine \| Synthesis, 2007, 17, 2608-2610. DOI: 10.1055/s-2007-983826
A Chemiluminescence nanosensor to monitor lipid peroxidation N. Baker, G. M. Greenway, R. A. Wheatley and C. Wiles \| Analyst, 2007, 132, 104-106.
Parallel synthesis in an EOF-based micro reactor C. Wiles and P. Watts \| Chem. Commun., 2007, 4928-4930. DOI: 10.1039/b712546a.
Improving chemical synthesis using flow reactors C. Wiles and P. Watts \| Expert Opinion on Drug Discovery, 2007, 2(11), 1487-1503.
Immobilisation of thermophilic enzymes in miniaturised flow reactors A. M. Hickey, L. Marle, T. McCreedy, P. Watts, G. M. Greenway and J. A. Lit \|
An efficient, continuous flow technique for the chemoselective synthesis of thioacetals C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron Lett., 2007, 48, 736
Separation of [18F]fluoride ion from proton-irradiated [18O]water within an EOF-driven micro-reactor S. Lu, M. J. Gilde, A. Prak, P. Watts and V. Pike, J. Label \|
The Synthesis of deuterium labelled amides within micro reactors J. Hooper and P. Watts, J. Label \| Compd. Radiopharm, 2007, 50, 189-196.
The use of solid-supported reagents for the multi-step synthesis of a combinatorial array of analytically pure α and β-unsaturated compounds in miniaturized flow reactors C. Wiles, P. Watts and S. J. Haswell \| Lab Chip, 2007, 7, 322-330.
Synthesis of analytically pure compounds in flow reactors C. Wiles and P. Watts \| Chem. Eng. Technol., 2007, 329-333. DOI:10.1002/ceat.200600323
Micro Reactors: A New Tool for the Synthetic Chemist C. Wiles and P. Watts \| Org. Biomol. Chem., 2007, 5, 727-732.
The use of electroosmotic flow as a pumping mechanism for semi-preparative scale continuous flow synthesis C. Wiles, P. Watts and S. J. Haswell \| Chem. Commun., 2007, 966-968.
Recent advances in synthetic micro reaction technology C. Wiles and P. Watts \| CChem. Commun., 2007 (5), 443-467
Scaling out of electrolyte free electrosynthesis in a micro-gap flow cell P. He, F. Marken, S.J. Haswell and P. Watts \| Lab Chip, 2007, 7,
Electrosynthesis of phenyl-2-propanone derivatives from benzyl bromides and acetic anhydride in an unsupported micro-flow cell electrolysis process P. He, P. Watts, S. J. Haswell and F. Marken \| Green Chem, 2007

2006

Isotopic labelling in micro reactors J. Hooper, P. Watts and C. Wiles \| J. Labelled Compounds and Radiopharmaceuticals, 2006, 49, 4, 377-420. (Conference Special Edition (Hinxton)). (pg 417*)
The use of solid-supported reagents in continuous flow reactors C. Wiles*, P. Watts and S. J. Haswell \| J. Labelled Compounds and Radiopharmaceuticals, 2006, 49, 4, 377-420. (Conference Special Edition (Hinxton)). (pg 419)
Synthesis and characterisation of immobilised Ruthenium complexes G. M. Greenway, A. Greenwood, P. Watts and C. Wiles \| J. Chem. Soc., Chem. Commun., 2006, (1), 85-87.
Self-Supported and clean one-step cathodic coupling of activated olefins with benzylbromide derivatives in a micro flow reactor P. He, F. Marken, S.J. Haswell and P. Watts \| P. He, F. Marken, S.J. Haswell and P. Watts, Angew. Chemie., Int. Ed. Eng.&#
Clean and selective oxidation of aromatic alcohols using silica-supported Jones reagent in a pressure-driven flow reactor C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron Lett., 2006, 47, 5261-5264.
Microreactor as tools for chemical research X. Zhang, C. Wiles, S. L. Painter, P. Watts and S. J. Haswell \| Chimica Oggi, Chemistry Today, 2006, 24, No. 2, 43-45.
Flow reactors for organic synthesis G. P. Wild, C. Wiles and P. Watts \| Letters in Organic Chemistry, 2006, 3, No. 6, 419-425
Towards paired and coupled electrode reactions for clean organic micro reactor electrosynthesis, C. A. Paddon, M. Atobe, T. Fuchigami, P. He, P. Watts, S. J. Haswell&# \| C. A. Paddon, M. Atobe, T. Fuchigami, P. He, P. Watts, S. J. Haswell&#

2005

Combinatorial synthesis in micro reactors P. Watts \| QSAR and Combinatorial Science, 2005, 24, 701-711
The preparation and reaction of carbanions within micro reactors C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Tetrahedron, 2005, 61, 10757.
Electrolyte free electroorganic synthesis: The cathodic dimerisation of 4-nitrobenzylbromide in a micro-gap flow cell P. He, P. Watts, S. J. Haswell and F. Marken \| Electrochemistry Communications
Microreactors for drug discovery: the importance of integrating chemical synthesis with real-time analytical detection P. Watts \| Anal. Bioanal. Chem., 2005, 382, 865-867.
The application of micro reactors for small scale organic synthesis P. Watts and S. J. Haswell \| Chem. Eng. Technol., 2005, 28, 290-301.
Acid catalysed synthesis and deprotection of dimethyl acetals in a miniaturised electroosmotic flow reactor C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron, 2005, 61, 5209-5217
The application of micro reactors for organic synthesis P. Watts and S. J. Haswell \| Chem. Soc. Rev., 2005, 34, 235-246.

2004

Exploration of a micro reactor for the synthesis of non carrier added 11C- and 18F-labelled carboxylic esters S. Lu, P. Watts, F. T. Chin, J. Hong, J. L. Musachio, E. Briard \|
Continuous flow micro reactors for drug discovery P. Watts \| Current Opinion in Drug Discovery and Development, 2004, 807.
Synthesis of 11C- and 18F-labeled carboxylic esters within a hydrodynamically driven micro reactor S. Lu, P. Watts, F. T. Chin, J. Hong, J. L. Musachio, E. Briard \|
Solid supported continuous flow synthesis in micro reactors using electroosmotic flow N. Nikbin and P. Watts \| OPRD, 2004, 8, 942-944.
Combinatorial synthesis in micro reactors P. Watts and S. J. Haswell \| Combinatorial Chemistry and High Throughput Screening, 2004&
An investigation into the use of silica supported bases within EOF based flow reactors C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron, 2004, 60, 8421.
Chemical Synthesis in micro reactors P. Watts \| Ingenieur Technik, 2004, 76, 555-559
Electrochemical effects related to synthesis in micro reactors operating under electrokinetic flow P. Watts, S. J. Haswell and E. Pombo-Villar \| Chemical Engineering Journal, 2004
Stereoselective alkylation of an Evans auxiliary derivative within a pressure driven micro reactor C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Lab Chip, 2004, 4, 171.
Benchmarking micro reactor applications H. Pennemann, P. Watts, S. J. Haswell, V. Hessel and H. Lowe \| OPRD, 2004
Organic synthesis in micro reactors X. Feng, S. J. Haswell and P. Watts \| Current Topics in Medicinal Chemistry, 2004
The application of microreactor technology for the synthesis of 1,2-azoles C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Org. Process Rev. Dev., 2004, 8, 28.

2003

Green Chemistry: Synthesis in Micro Reactors P. Watts and S. J. Haswell \| Green Chemistry, 2003, 5, 240-249.
Microfluidic combinatorial chemistry P. Watts and S. J. Haswell, \| Current Opinion in Chemical Biology, 2003, 7, 38
Continuous flow reactors for drug discovery P. Watts and S. J. Haswell \| Drug Discovery Today, 2003, 8, 586-593.
Solution phase synthesis of esters within a micro reactor C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Tetrahedron, 2003, 59, 10173.
On-chip separation of peptides prepared within a micro reactor V. George, P. Watts, S. J. Haswell and E. Pombo-Villar \|

2002

Investigation of racemisation in peptide synthesis within a micro reactor P. Watts, C. Wiles, S. J. Haswell and E. Pombo-Villar \| Lab Chip, 2002, 2, 141.
Solution phase synthesis of β-peptides using micro reactors, P. Watts, C. Wiles, S. J. Haswell and E. Pombo-Villar \| Tetrahedron, 2002, 58, 5427.
Micro reactors: principles and applications in organic synthesis P. D. I. Fletcher, S. J. Haswell, E. Pombo-Villar, B. H. Warrington, P. Watts \|
1,4-Addition of enolates to α and β-unsaturated ketones within a micro reactor C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Lab Chip, 2002, 2, 62.
The regioselective preparation of 1,3-diketones in a micro reactor C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| J. Chem. Soc., Chem. Commun., 2002, 1034.

2001

The aldol reaction of silyl enol ethers within a micro reactor C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Lab Chip, 2001, 1, 100.
The synthesis of peptides in micro reactors P. Watts, C. Wiles, S. J. Haswell, E. Pombo-Villar and P. Styring \| J. Chem. Soc., Chem. Commun., 2001, 990.
The application of micro reactors to synthetic chemistry S. J. Haswell, R. J. Middleton, B. O'Sullivan, V. Skelton, P. Watts \|

Biphasic PNA hydrolysis Dr. Charlotte Wiles, Dr Bongkot Ngamsom \| 2010, 12-13	Download
Continuous flow synthesis of β-Peptides within labtrix® reactors Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010, 12-13	Download
High-throughput synthesis of alkyl amides within labtrix reactors Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010, 11-01	Download
Continuous flow transfer hydrogenations Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010,10-20	Download
Manipulation of Grignard reagents within labtrix reactors Dr. Charlotte Wiles \| 2010, 20-09	Download
Knoevenagel condensation Dr. Charlotte Wiles \| 2010-08-23	Download
Ester hydrolyses Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010-07-30	Download
Continuous flow esterifications Dr. Charlotte Wiles & Dr. Bongkot Ngamsom \| 2010-07-26	Download
The use of static micro mixers within labtrix® micro reactors Dr. Charlotte Wiles \| 2010, 06-07	Download
Scale out of chemical synthesis in flow reactors Dr. P.Watts \| 2010, 07-01	Download
The scale-up of chemical sythesis using micro reactors C.Wiles and P.Watts \| Chemistry Today, 2010, 4-6

Continues flow organic synthesis: a tool for the modern medicinal chemist C. Wiles & P.Watts \| Future Medicinal Chemistry, 2009, 1(9), 1593-1612
The use of micro reactors as tools for the high-throughput synthesis of small organic molecule libraries C. Wiles \| Speciality Chemicals Magazine, 2009, 29(7), 40-41
A microreactor for the study of biotransformations by a cross-linked gamma-lactamase enzyme A. M. Hickey, B. Ngamsom, C. Wiles, G. M. Greenway, P. Watts and J. A. Littl \| Biotechnology J., 2009, 4(4), 510-516.
The development and evaluation of a continuous flow process for the lipase-mediated oxidation of alkenes C. Wiles, M. J. Hammond and P. Watts \| Belstein Journal Organic Chemistry, 2009
Enhanced chemical synthesis in flow reactors C.Wiles and P.Watts \| Chimica Oggi, 2009, 27, 3, 34-36.

An efficient, chemoselective technique for the continuous flow synthesis of thioacetals C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron Lett., 2007, 48, 7362-7365. DOI: 10.1016/j.tetlet.2007.08.027.
An expedient, scalable synthesis of the natural product L-anserine \| Synthesis, 2007, 17, 2608-2610. DOI: 10.1055/s-2007-983826
A Chemiluminescence nanosensor to monitor lipid peroxidation N. Baker, G. M. Greenway, R. A. Wheatley and C. Wiles \| Analyst, 2007, 132, 104-106.
Parallel synthesis in an EOF-based micro reactor C. Wiles and P. Watts \| Chem. Commun., 2007, 4928-4930. DOI: 10.1039/b712546a.
Improving chemical synthesis using flow reactors C. Wiles and P. Watts \| Expert Opinion on Drug Discovery, 2007, 2(11), 1487-1503.
Immobilisation of thermophilic enzymes in miniaturised flow reactors A. M. Hickey, L. Marle, T. McCreedy, P. Watts, G. M. Greenway and J. A. Lit \|
An efficient, continuous flow technique for the chemoselective synthesis of thioacetals C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron Lett., 2007, 48, 736
Separation of [18F]fluoride ion from proton-irradiated [18O]water within an EOF-driven micro-reactor S. Lu, M. J. Gilde, A. Prak, P. Watts and V. Pike, J. Label \|
The Synthesis of deuterium labelled amides within micro reactors J. Hooper and P. Watts, J. Label \| Compd. Radiopharm, 2007, 50, 189-196.
The use of solid-supported reagents for the multi-step synthesis of a combinatorial array of analytically pure α and β-unsaturated compounds in miniaturized flow reactors C. Wiles, P. Watts and S. J. Haswell \| Lab Chip, 2007, 7, 322-330.
Synthesis of analytically pure compounds in flow reactors C. Wiles and P. Watts \| Chem. Eng. Technol., 2007, 329-333. DOI:10.1002/ceat.200600323
Micro Reactors: A New Tool for the Synthetic Chemist C. Wiles and P. Watts \| Org. Biomol. Chem., 2007, 5, 727-732.
The use of electroosmotic flow as a pumping mechanism for semi-preparative scale continuous flow synthesis C. Wiles, P. Watts and S. J. Haswell \| Chem. Commun., 2007, 966-968.
Recent advances in synthetic micro reaction technology C. Wiles and P. Watts \| CChem. Commun., 2007 (5), 443-467
Scaling out of electrolyte free electrosynthesis in a micro-gap flow cell P. He, F. Marken, S.J. Haswell and P. Watts \| Lab Chip, 2007, 7,
Electrosynthesis of phenyl-2-propanone derivatives from benzyl bromides and acetic anhydride in an unsupported micro-flow cell electrolysis process P. He, P. Watts, S. J. Haswell and F. Marken \| Green Chem, 2007

Isotopic labelling in micro reactors J. Hooper, P. Watts and C. Wiles \| J. Labelled Compounds and Radiopharmaceuticals, 2006, 49, 4, 377-420. (Conference Special Edition (Hinxton)). (pg 417*)
The use of solid-supported reagents in continuous flow reactors C. Wiles*, P. Watts and S. J. Haswell \| J. Labelled Compounds and Radiopharmaceuticals, 2006, 49, 4, 377-420. (Conference Special Edition (Hinxton)). (pg 419)
Synthesis and characterisation of immobilised Ruthenium complexes G. M. Greenway, A. Greenwood, P. Watts and C. Wiles \| J. Chem. Soc., Chem. Commun., 2006, (1), 85-87.
Self-Supported and clean one-step cathodic coupling of activated olefins with benzylbromide derivatives in a micro flow reactor P. He, F. Marken, S.J. Haswell and P. Watts \| P. He, F. Marken, S.J. Haswell and P. Watts, Angew. Chemie., Int. Ed. Eng.&#
Clean and selective oxidation of aromatic alcohols using silica-supported Jones reagent in a pressure-driven flow reactor C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron Lett., 2006, 47, 5261-5264.
Microreactor as tools for chemical research X. Zhang, C. Wiles, S. L. Painter, P. Watts and S. J. Haswell \| Chimica Oggi, Chemistry Today, 2006, 24, No. 2, 43-45.
Flow reactors for organic synthesis G. P. Wild, C. Wiles and P. Watts \| Letters in Organic Chemistry, 2006, 3, No. 6, 419-425
Towards paired and coupled electrode reactions for clean organic micro reactor electrosynthesis, C. A. Paddon, M. Atobe, T. Fuchigami, P. He, P. Watts, S. J. Haswell&# \| C. A. Paddon, M. Atobe, T. Fuchigami, P. He, P. Watts, S. J. Haswell&#

Combinatorial synthesis in micro reactors P. Watts \| QSAR and Combinatorial Science, 2005, 24, 701-711
The preparation and reaction of carbanions within micro reactors C. Wiles, P. Watts, S. J. Haswell and E. Pombo-Villar \| Tetrahedron, 2005, 61, 10757.
Electrolyte free electroorganic synthesis: The cathodic dimerisation of 4-nitrobenzylbromide in a micro-gap flow cell P. He, P. Watts, S. J. Haswell and F. Marken \| Electrochemistry Communications
Microreactors for drug discovery: the importance of integrating chemical synthesis with real-time analytical detection P. Watts \| Anal. Bioanal. Chem., 2005, 382, 865-867.
The application of micro reactors for small scale organic synthesis P. Watts and S. J. Haswell \| Chem. Eng. Technol., 2005, 28, 290-301.
Acid catalysed synthesis and deprotection of dimethyl acetals in a miniaturised electroosmotic flow reactor C. Wiles, P. Watts and S. J. Haswell \| Tetrahedron, 2005, 61, 5209-5217
The application of micro reactors for organic synthesis P. Watts and S. J. Haswell \| Chem. Soc. Rev., 2005, 34, 235-246.