Flow Microwave Technology and Microreactors in Synthesis
Ian R. Baxendale A E , Christian Hornung B , Steven V. Ley C , Juan de Mata Muñoz Molina C and Anders Wikström DA Department of Chemistry, University of Durham, South Road, Durham, DH1 3LE, UK.
B CSIRO Materials Science & Engineering, Clayton South, Vic. 3169, Australia.
C Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
D Biotage Sweden AB, Kungsgatan 76, SE-753 18 Uppsala, Sweden.
E Corresponding author. Email: i.r.baxendale@durham.ac.uk
Australian Journal of Chemistry 66(2) 131-144 https://doi.org/10.1071/CH12365
Submitted: 2 August 2012 Accepted: 5 September 2012 Published: 8 October 2012
Abstract
A bespoke microwave reactor with a glass containment cell has been developed for performing continuous flow reactions under microwave heating. The prototype unit has been evaluated using a series of standard organic chemical transformations enabling scale-up of these chemical processes. As part of the development, a carbon-doped PTFE reactor insert was utilized to allow the heating of poorly absorbing reaction media, increasing the range of solvents and scope of reactions that can be performed in the device.
References
[1] (a) P. Lidström, J. P. Tierney, B. Wathey, J. Westman, Tetrahedron 2001, 57, 9225.| Crossref | GoogleScholarGoogle Scholar |
(b) C. O. Kappe, A. Stadler, Microwaves in Organic and Medicinal Chemistry 2005 (Wiley-VCH: Weinheim).
(c) J. P. Tierney, P. Lidström (Eds), Microwave-assisted Organic Synthesis 2005 (Blackwell Publishing Ltd: Oxford).
[2] (a) V. Hessel, Chem. Eng. Technol. 2009, 32, 1655.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtlCrsL%2FN&md5=9be5b449d3cda541087eaff28ba63b21CAS |
(b) M. Baumann, I. R. Baxendale, S. V. Ley, Mol. Divers. 2011, 15, 613.
| Crossref | GoogleScholarGoogle Scholar |
(c) A. Sachse, A. Galarneau, B. Coq, F. Fajula, New J. Chem. 2011, 35, 259.
| Crossref | GoogleScholarGoogle Scholar |
[3] (a) L. F. Raveglia, G. A. M. Giardina, Future Med. Chem. 2009, 1, 1019.
| 1:CAS:528:DC%2BD1MXhsVChs77K&md5=fe1865f485e631d2081b78600743b696CAS |
(b) W. G. Devine, N. E. Leadbeater, ARKIVOC 2011, V, 127.
(c) S. V. Ley, I. R. Baxendale, in Systems Chemistry (Eds M. G. Hicks, C. Kettner) 2009, Proceedings of the Beilstein-Institut Workshop, 26–30 May, 2008, Bozen, Italy, 65–85. Available at http://www.beilsteininstitut.de/Bozen2008/Proceedings/Ley/Ley.pdf
(d) K. Geyer, P. H. Seeberger, in Systems Chemistry (Eds M. G. Hicks, C. Kettner) 2009, Proceedings of the Beilstein-Institut Workshop, 26–30 May, 2008, Bozen, Italy, 87–107. Available at http://www.beilstein-institut.de/Bozen2008/Proceedings/Seeberger/Seeberger.pdf
(e) S. V. Ley, I. R. Baxendale, Chimia 2008, 62, 162.
| Crossref | GoogleScholarGoogle Scholar |
[4] (a) I. R. Baxendale, M. R. Pitts, Chimica Oggi, Chemistry Today 2006, 24, 241.
(b) I. R. Baxendale, J. J. Hayward, S. V. Ley, Comb. Chem. High Throughput Screen. 2007, 10, 802.
| Crossref | GoogleScholarGoogle Scholar |
(c) T. N. Glasnov, C. O. Kappe, Macromol. Rapid Commun. 2007, 28, 395.
| Crossref | GoogleScholarGoogle Scholar |
(d) J. R. Schmink, C. M. Kormos, W. G. Devine, N. E. Leadbeater, Org. Process Res. Dev. 2010, 14, 205.
| Crossref | GoogleScholarGoogle Scholar |
(e) T. N. Glasnov, C. O. Kappe, Chem. – Eur. J. 2011, 17, 11956.
| Crossref | GoogleScholarGoogle Scholar |
[5] (a) S. Saaby, I. R. Baxendale, S. V. Ley, Org. Biomol. Chem. 2005, 3, 3365.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXpsFWntrg%3D&md5=c3cbb44380277959b6f54257388d6f44CAS |
(b) I. R. Baxendale, J. Deeley, C. M. Griffiths-Jones, S. V. Ley, S. Saaby, G. K. Tranmer, Chem. – Eur. J. 2006, 12, 4407.
| Crossref | GoogleScholarGoogle Scholar |
(c) C. J. Smith, J. Iglesias-Sigüenza, I. R. Baxendale, S. V. Ley, Org. Biomol. Chem. 2007, 5, 2758.
| Crossref | GoogleScholarGoogle Scholar |
(d) J. Sedelmeier, S. V. Ley, H. Lange, I. R. Baxendale, Eur. J. Org. Chem. 2009, 4412.
| Crossref | GoogleScholarGoogle Scholar |
[6] M. C. Bagley, R. L. Jenkins, M. C. Lubinu, C. Mason, R. Wood, J. Org. Chem. 2005, 70, 7003.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmsVahs74%3D&md5=86e3f9a119d6e01a967cc8660673615aCAS |
[7] A. Debache, R. Boulcina, A. Belfaitah, S. Rhouati, B. Carboni, Synlett 2008, 2008, 509.
| Crossref | GoogleScholarGoogle Scholar |
[8] See http://www.uniqsis.com/paProductsDetail.aspx?ID=ACC_MIX for details on the baffled mixer chip (verified September 2012).
[9] (a) H. R. Sahoo, J. G. Kralj, K. F. Jensen, Angew. Chem. Int. Ed. 2007, 46, 5704.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXosFOktL4%3D&md5=d8bdf220639d5d19bc63051982bec656CAS |
(b) J. Wiss, C. Fleury, C. Heuberger, U. Onken, M. Glor, Org. Process Res. Dev. 2007, 11, 1096.
| Crossref | GoogleScholarGoogle Scholar |
(c) K. Yamatsugu, S. Kamijo, Y. Suto, M. Kanai, M. Shibasaki, Tetrahedron Lett. 2007, 48, 1403.
| Crossref | GoogleScholarGoogle Scholar |
(d) H. Lebel, O. Leogane, Org. Lett. 2006, 8, 5717.
| Crossref | GoogleScholarGoogle Scholar |
(e) M. Baumann, I. R. Baxendale, S. V. Ley, N. Nikbin, C. D. Smith, J. P. Tierney, Org. Biomol. Chem. 2008, 6, 1577.
| Crossref | GoogleScholarGoogle Scholar |
(f) M. Baumann, I. R. Baxendale, S. V. Ley, N. Nikbin, C. D. Smith, Org. Biomol. Chem. 2008, 6, 1587.
| Crossref | GoogleScholarGoogle Scholar |
[10] (a) V. Singh, S. Kaur, V. Sapehiyi, J. Singh, G. L. Kad, Catal. Commun. 2005, 6, 57.For selected examples, see:
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtFanu7%2FP&md5=1f17d7c0492a10862744fed84a45cc7bCAS |
(b) M. S. Manhas, S. N. Ganguly, S. Mukherjee, A. K. Jain, A. K. Bose, Tetrahedron Lett. 2006, 47, 2423.
| Crossref | GoogleScholarGoogle Scholar |
(c) B. Tyagi, M. K. Mishra, R. V. Jasra, J. Mol. Catal. A – Chem. 2007, 276, 47.
| Crossref | GoogleScholarGoogle Scholar |
(d) Y. Reddy, S. Thirupathi, S. Vijayakumar, P. Crooks, P. Dasari, P. Reddy, P. Narsimha, B. Rajitha, Synthetic Commun. 2008, 38, 2082.
| Crossref | GoogleScholarGoogle Scholar |
(e) A. Sinhamahapatra, N. Sutradhar, S. Pahari, H. C. Bajaj, A. B. Panda, Appl. Catal. A – Gen. 2011, 394, 93.
| Crossref | GoogleScholarGoogle Scholar |
(f) Q. Zhang, S. Zhang, Y. Deng, Green Chem. 2011, 13, 2619.
| Crossref | GoogleScholarGoogle Scholar |
(g) J. Zak, D. Ron, E. Riva, H. P. Harding, B. C. S. Cross, I. R. Baxendale, Chem. – Eur. J. 2012, 18, 9901.
| Crossref | GoogleScholarGoogle Scholar |
[11] (a) S. V. Ley, A. G. Leach, R. I. Storer, J. Chem. Soc., Perkin Trans. 1 2001, 358.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXhtFalsL8%3D&md5=c94e747e48606b1752f3539165106081CAS |
(b) R. Martínez-Palou, J. Mex. Chem. Soc. 2007, 51, 252.
(c) N. E. Leadbeater, H. M. Torenius, in Microwaves in Organic Synthesis (Ed. A. Loupy) 2008, Ch. 7, pp. 327–361 (Wiley-VCH: Weinheim).
[12] D. Obermayer, B. Gutmann, C. O. Kappe, Angew. Chem. Int. Ed. 2009, 48, 8321.Weflon is Milestone's proprietary microwave absorbing carbon-impregnated Teflon material; Si/C, see:
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXht12htb%2FE&md5=d62903d4379903bf42f49b2606d842d1CAS |
[13] (a) G. E. Keck, J. B. Yates, J. Am. Chem. Soc. 1982, 104, 5829.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38Xls1Wrt7Y%3D&md5=1917eabd8967878c403993b49580b8cbCAS |
(b) S. D. Burke, W. F. Fobare, D. M. Armistead, J. Org. Chem. 1982, 47, 3348.
| Crossref | GoogleScholarGoogle Scholar |
(c) F. Le Guyader, B. Quiclet-Sire, S. Seguin, S. Z. Zard, J. Am. Chem. Soc. 1997, 119, 7410.
| Crossref | GoogleScholarGoogle Scholar |
[14] P.-J. Shim, H.-D. Kim, Tetrahedron Lett. 1998, 39, 9517.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXotFWks74%3D&md5=3000c344cabcfa6bd89674468b65c389CAS |
[15] (a) T. L. Mindt, R. Schibli, J. Org. Chem. 2007, 72, 10247.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlOntbbE&md5=e3e245fd9f8e39e44ac1a261d95f8c63CAS |
(b) H. Harkat, A. Y. Dembelé, J.-M. Weibel, A. Blanc, P. Pale, Tetrahedron 2009, 65, 1871.
| Crossref | GoogleScholarGoogle Scholar |
(c) J. Alemán, V. del Solar, L. Cubo, A. G. Quiroga, C. N. Ranninger, Dalton Trans. 2010, 10601.
| Crossref | GoogleScholarGoogle Scholar |
[16] G. Sun, C. Cheng, K. L. Wooley, Macromolecules 2007, 40, 793.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXptFOkug%3D%3D&md5=94c20437852b60991744ce6d338707a0CAS |
[17] C. R. Sarko, in Microwave-assisted Organic Synthesis (Eds J. P. Tierney, P. Lidström) 2005, Ch. 8, pp. 222–236 (Blackwell Publishing Ltd: Oxford).
[18] B. L. Hayes, Microwave Synthesis: Chemistry at the Speed of Light 2002 (CEM Publishing: Matthews, NC).
[19] J. Habermann, S. V. Ley, J. S. Scott, J. Chem. Soc., Perkin Trans. 1 1999, 10, 1253.
| Crossref | GoogleScholarGoogle Scholar |
[20] (a) P. F. Schuda, W. A. Price, J. Org. Chem. 1987, 52, 1972.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXkt1eisb8%3D&md5=7ee9c88c364b5f565e02637a45765393CAS |
(b) I. R. Baxendale, A.-L. Lee, S. V. Ley, J. Chem. Soc., Perkin Trans. 1 2002, 1850.
| Crossref | GoogleScholarGoogle Scholar |
[21] (a) A. S. Zentiva, H. Stepankova, P. Pihera, J. Hajicek, A Method of Preparation of Ramipril, WO patent, 121084, 2005.
(b) V. Teetz, R. Geiger, H. Baul, Tetrahedron Lett. 1984, 25, 4479.
| Crossref | GoogleScholarGoogle Scholar |
(c) M. Baumann, I. R. Baxendale, S. V. Ley, N. Nikbin, Beilstein J. Org. Chem. 2011, 7, 442.
| Crossref | GoogleScholarGoogle Scholar |
[22] H. Urbach, X. Uenning, Tetrahedron 1985, 26, 1839.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2MXkslWitrs%3D&md5=4dcdbae2b8efb135ce0bb0283a627804CAS |
[23] Continuous Flow Catalytic Reactions with FlowCAT. Available at http://www.helgroup.com/reactor-systems/hydrogenation-catalysis/flowcat-highpressure-flowchemistry-in-a-compact-unit/
[24] J. M. Hawkins, Trickle Bed Flow Hydrogenation Using Shallow Beds of Fine Catalyst Particles: Enhanced Diastereoselectivity, Purity Control, and Catalyst Activity Relative to Batch Hydrogenations, Abstracts of Papers, 242nd ACS National Meeting & Exposition, Denver, CO, United States, 28 August–1 September 2011.
[25] Glass beads acid-washed; 212–300 μm available from Sigma–Aldrich cat. no. G1277 and 150–212 μm available from Sigma–Aldrich cat. no. G1145.