Initial results from a commercial continuous flow microwave reactor for scale-up

Chimica Oggi

Volumn 25, Issue 2, 2007, Pages 16-19

  Moseley, Jonathan D ^a   Lawton, Simon J ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34249996777     PISSN: 0392839X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (40)

1. C. O. Kappe, A. Stadler, "Microwaves in Organic and Medicinal Chemistry", Wiley-VCH, Weinheim, 2005.
2. (a) "Microwave Assisted Organic Synthesis", (Eds.: J. P. Tierney, P. Lidström), Blackwell, Oxford, 2005;
3. (b) "Microwaves in Organic Synthesis", (Ed.; A. Loupy), Wiley-VCH, Weinheim, 2002;
4. (c) B. L. Hayes, "Microwave Synthesis: Chemistry at the Speed of Light", CEM, Matthews, 2002.
5. (a) C. O. Kappe, Angew. Chem. Int. Ed. 43, 6250-6284, (2004).
6. (b) B. L. Hayes, Aldrichimica Acta 37, 66-76 (2004).
7. (c) M. Nüchter, B. Ondruschka, W. Bonrath, A. Gum, Green Chem. 6, 128-141 (2004).
8. (d) P. Lidström, J. Tierney, B. Wathey, J. Westman, Tetrahedron 57, 9225-9283 (2001).
9. (e) L. Perreux, A. Loupy, Tetrahedron 57, 9199-9223 (2001).
10. (a) T. M. Bornard, G. S. Vanier, M. J. Collins, Org. Process Res. Dev. 10, 1233-1237 (2006).
11. (b) N. E. Leadbeater, V. A. Williams, T. M. Barnard, M. J. Collins, Synlett, 2953-2958 (2006).
12. (c) N. E. Leadbeater, V. A. Williams, T. M. Barnard, M. J. Collins, Org. Process Res. Dev. 10, 833-837 (2006).
13. (d) M. R. Pitts, P. McCormack, J. Whittall, Tetrahedron 62, 4705-4708 (2006).
14. (e) B. A. Roberts, C. R. Strauss, Acc. Chem. Res. 38, 653-661 (2005).
15. (f) A. Stadler, B. H. Yousefi, D. Dallinger, P. Walla, E. Van der Eycken, N. Kaval, C. Kappe, Org. Process Res. Dev. 7, 707-716 (2003).
16. (g) K. D. Raner, C. R. Strauss, R. W. Trainor, J. S. Thorn, J. Org. Chem. 60, 2456-2460 (1995).
17. For an excellent brief discussion, see Ref. 1, pp. 82-87. See also:- (a) Ref. 3a, p. 6275. (b) Ref. 3b, p. 71. (c) Ref 3c, pp. 136-138.
18. T. Cablewski, A. F. Faux, C. R. Strauss, J. Org. Chem. 59, 3408-3412 (1994).
19. (a) W. S. Bremner, M. G. Organ, J. Comb. Chem. 9, 14-16 (2007).
20. (b) I. R. Baxendale, M. R. Pitts, Chemistry Today 24, (3), 41-45 (2006).
21. (c) T. Schwalbe, K. Simons, Chemistry Today 24, (2), 56-61 (2006).
22. (d) R. J. J. Jachuck, D. K. Selvaraj, R. S. Varma, Green Chem. 8, 29-33 (2006).
23. (e) M. C. Bagley, R. L. Jenkins, M. C. Lubinu, C. Mason, R. Wood, J. Org. Chem. 70, 7003-7006 (2005).
24. (f) N. S. Wilson, C. R. Sarko, G. P. Roth, Org. Process Res. Dev. 8, 535-538 (2004).
25. (g) W.-C. Shieh, M. Lozanov, O. Repic, Tetrahedron Lett. 44, 6943-6945 (2003).
26. (h) W.-C. Shieh, S. Dell, O. Repic, Tetrahedron Lett. 43, 5607-5609 (2002).
27. (i) B. M. Khadilkar, V. R. Madyar, Org. Process Res. Dev. 5, 452-455 (2001).
28. (j) J. Marquie, G. Salmoria, M. Poux, A. Laporterie, J. Dubac, N. Roques, Ind. Eng. Chem. Res. 40, 4485-4490 (2001).
29. (k) K. G. Kabza, B. R. Chapados, J. E. Gestwicki, J. L. McGrath, J. Org. Chem. 65, 1210-1214 (2000).
30. Although a number of the above articles and reviews have confidently claimed that continuous flow microwaves can process 10's L/hr, and that kg scale production can be achieved, there are few reported examples of this for either prototype or commercial instruments. Synthesis up to ∼1 kg is certainly possible with several commercially available microwave reactors (see ref. 4). For ongoing investigations into scale-up and through-puts on true pilot plant scale, see the work of B. Ondruschka (Jena) and D. Bogdal (Krakow).
31. nd March 2006.
32. For a discussion of possible microwave effects, see the relevant sections in refs. 2 and 3 and specifically: A. de la Hoz, A. Diaz-Ortez, A. Moreno, Chem. Soc. Rev. 34, 164-178 (2005).
33. J. D. Moseley, R. F. Sankey, O. N. Tang and J. P. Gilday, Tetrahedron 62, 4685-4689 (2006).
34. Weflon® is PTFE impregnated with graphite to aid in heating in microwave reactors. See www.milestonesci.com/faq-START.php.
35. nd edition), Prentice Hall International, Englewood Cliffs, New Jersey, pp. 712 - 737 (1992).
36. This discrepancy was caused by variation in the pump speed (perhaps affected by the variation in viscosity between neat solvent and reaction mixture), and by unfamiliarity with the pump settings. Both could easily be adjusted for longer runs to achieve the desired steady-state conditions.
37. th March 2007.
38. For example, see the continuous flow reactors offered by the following:-(a) www.mrsp.net.
39. (b) www.syrris.com.
40. (c) www.vapourtec.co.uk.