Gas Reactors

Gas reactors used continuous flow chemical synthesis

Our expertise in developing new enabling tools for continuous flow processes has led to significant advances in the way we conduct our synthesis programmes. We have delivered new concepts; from prototype to fully operational bench-top units. A novel tube-in-tube flow gas reactor (designed in house) has now been developed into a commercial product with Cambridge Reactor Design [1].

The use of gases or volatile components as reagents is often not ideal in batch mode operation due to safety concerns. However, using our semi-permeable membrane flow reactor device we have created a robust gas reactor that allows controlled solubilisation of gaseous reagents into a liquid stream to achieve a wide selection of reactions. We have disclosed a diverse range of applications using these devices to carryout ozonolysis [2], carboxylations [3], hydrogenations [4, 5], Glaser oxidative couplings [6],carbonylations [7], nucleophilic addition of ammonia [1, 8, 9], hydroformylations using Syngas [10], coupling Heck reactions using ethylene [11, 12], as well as  aerobic anti-markovnikov oxidative processes [13]. We also developed a bespoke reactor system for the “spray ozonolysis” of one of the intermediate used in the synthesis of an unnatural amino acid [14].


1. Flow synthesis using gaseous ammonia in a Teflon AF-2400 tube-in-tube reactor: Paal–Knorr pyrrole formation and gas concentration measurement by inline flow titration P.B. Cranwell,  M. O’Brien,  D. L. Browne,  P. Koos,  A. Polyzos,  M. Peña-López,
 S.V. Ley Org. Biomol. Chem201210, 5774-5779,

2. Flow ozonolysis using a semi-permeable Teflon AF-2400 membrane to effect gas-liquid contact M.O’Brien, I.R. Baxendale, S.V. Ley Org. Lett. 2010, 12, 1596-1598.

3. The continuous flow synthesis of carboxylic acids using CO2 in a tube-in-tube gas permeable membrane reactor A. Polyzos, M. O’Brien, T.P. Petersen, I.R. Baxendale, S.V. Ley Angew. Chem. Int. Ed. 2011, 50, 1190-1193.

4. Asymmetric homogenous hydrogenation in flow using tube-in-tube reactor  S. Newton, S.V. Ley, E.C. Arce, D. Grainger Adv. Synth. Catal. 2012354, 1805-1812.

5. Hydrogenation in flow: homogenous and heterogeneous catalysts using Teflon AF-2400 to effect gas-liquid contact at elevated pressure M. O’Brien, N. Taylor, A. Polyzos, I.R. Baxendale, S.V. Ley Chem. Sci. 2011, 2, 1250-1257.

6. The oxygen-mediated synthesis of 1,3-butadiynes in continuous flow: using Teflon AF-2400 to effect gas/liquid contact T.P. Peterson, A. Polyzos, M. O’Brien, T. Ulven, I.R. Baxendale, S.V. Ley ChemSusChem 2012, 5, 274-277.

7. Teflon AF-2400 mediated gas-liquid contact in continuous flow methoxycarbonylations and in-line FTIR measurement of CO concentration P. Koos, U. Gross, A. Polyzos, M. O’Brien, I.R. Baxendale, S.V. Ley Org. Biomol. Chem. 20119, 6903-6908.

8. Continuous-flow processing of gaseous ammonia using a Teflon AF-2400 tube-in-tube reactor: synthesis of thioureas and in-line titrations D.L. Browne, M. O’Brien, P. Koos, P.B. Cranwell, A. Polyzos, S.V. Ley Synlett 201223, 1402-1406.

9. Scaling-up of continuous flow processes with gases using a tube-in-tube reactor: in-line titrations and fanetizole synthesis with ammonia J. Pastre, D.L. Browne, M. O’Brien and S.V. Ley, Org. Proc. Res. Dev201317, 1183-1191.

10. Syngas-mediated C-C bond formation in flow: selective rhodium-catalysed hydroformylation of styrenes S. Kasinathan, S.L. Bourne, P. Tolstoy, P. Koos, M. O’Brien, R.W. Bates, I.R. Baxendale, S.V. Ley Synlett 2011, 2648-2651.

11. The continuous flow synthesis of styrenes using ethylene in a palladium-catalysed Heck cross-coupling reaction S.L. Bourne, P. Koos, M. O’Brien, B. Martin, B. Schenkel, I.R. Baxendale, S.V. Ley  Synlett 2011, 2643-2647

12. Flow chemistry syntheses of styrenes, unsymmetrical stilbenes and branched aldehydes S.L. Bourne, M. O’Brien, S. Kasinathan, P. Koos, P. Tolstoy, D.X. Hu, R.W. Bates, B. Martin, B. Schenkel, S.V. Ley, ChemCatChem.20135, 159-172.

13.  A continuous flow solution to achieving efficient, aerobic anti-Markovnikov Wacker oxidation S.L. Bourne, S.V. Ley, Adv. Synth. Catal2013355, 1905-1910.

14. A flow based synthesis of 2-aminoadamantane-2-carboyxlic acid
C. Battilocchio, I.R. Baxendale, M. Biava, M.O. Kitching and S.V. Ley, Org. Proc. Res. Dev201216, 798-810.

15. Flow Chemistry: Intelligent Processing of Gas-Liquid Transformations using a Tube-in-Tube Reactor M. Brzozowski, M. O’Brien, S.V. Ley, A. Polyzos, Acc. Chem. Res201548, 349-362