A microreactor for microwave-assisted capillary (continuous flow) organic synthesis

Journal of the American Chemical Society

Volumn 127, Issue 22, 2005, Pages 8160-8167

  Comer, Eamon ^a   Organ, Michael G ^a  

^a YORK UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

CAPILLARY FLOW; CHEMICAL REACTORS; IRRADIATION; LAMINAR FLOW; PALLADIUM; SYNTHESIS (CHEMICAL); THIN FILMS;

METAL CATALYSTS; MICROWAVE IRRADIATIONS; ORGANIC SYNTHESIS; RING-CLOSING METATHESIS (RCM);

MICROWAVES;

METAL; PALLADIUM;

ARTICLE; CATALYSIS; CATALYST; CROSS COUPLING REACTION; FILM; LAMINAR FLOW; MICROWAVE RADIATION; ORGANIC CHEMISTRY; REACTION TIME; REACTOR; RING CLOSING METATHESIS; SOLID; SUZUKI REACTION; SYNTHESIS; SYRINGE;

EID: 20444412378     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0512069     Document Type: Article

References (34)

1. For recent reviews on the use of microwave irradiation in organic synthesis, see: (a) Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250-6284.
2. (b) Nüchter, M.; Ondruschka, B.; Bonrath, W.; Gum, A. Green Chem. 2004, 6, 128-141.
3. (c) Swamy, K. M. K.; Yeh, W.-B.; Lin, M.-J.; Sun, C.-M. Curr. Med. Chem. 2003, 10, 2403-2423.
4. (d) Wathey, B.; Tierney, J.; Lidstrom, P.; Westman, J. Drug Discovery Today 2002, 7, 373-380.
5. (e) Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001, 57, 9225-9283.
6. For reviews on the use of microreactors related to organic synthesis, see: (a) Pennemann, H.; Watts, P.; Haswell, S. J.; Hessel, V.; Loewe, H. Org. Process Res. Dev. 2004, 8, 422-439.
7. (b) Fletcher, P. D. I.; Haswell, S. J.; Pombo-Villar, E.; Warrington, B. H.; Watts, P.; Wong, S. Y. F.; Zhang X. Tetrahedron 2002, 58, 4735-4757.
8. (c) Haswell, S. J.; Middleton, R. J.; O'Sullivan, B.; Skelton, V.; Watts, P.; String, P. Chem Commun. 2001, 391-398.
9. Manz, A.; Harrison, D. J.; Verpoorte, E. M. J.; Fettinger, J. C.; Luedi, H.; Widmer, H. M. Chimia 1991, 45, 103-105.
10. There exists one example of a heated microreaction using a Peltier heater, see: Garcia-Egido, E.; Wong, S. Y. F.; Warrington, B. H. Lab Chip 2002, 2, 31-33.
11. We are aware of a large-scale, continuous flow microwave cell capable of performing multigram synthetic transformations, see: Wilson, N. S.; Sarko, C. R.; Roth, G. P. Org. Process Res. Dev. 2004, 8, 535-538.
12. He, P.; Haswell, S. J.; Fletcher, P. D. I. Lab Chip 2004, 4, 38-41.
13. He, P.; Haswell, S. J.; Fletcher, P. D. I. Appl. Catal., A 2004, 274, 111-114.
14. Organ, M. G.; Comer, E. U.S. Provisional Patent 60/605,505, 2004.
15. Organ, M. G. Personal communications with microwave designers and engineers at Biotage Inc., Upsalla, Sweden.
16. 1H NMR spectroscopy.
17. These and subsequent reactions were all performed with an MD-2000 Digital Readout microwave leakage detector directly focused on the microwave cavity (top and bottom) and the top of the microwave device including the inlet lines from the syringes to monitor any stray MW irradiation. Irradiation levels were found to well below acceptable safety standards.
18. Stadler, A.; Kappe, C. A. Org. Lett. 2002, 4, 3541-3543. In this report it was found that Pd-catalyzed coupling reactions run at high temperature led to catalyst desomposition and that the Pd black formed left a similar thin film on the glass in regular microwave vessels. However, lower yields were reported in that case in comparison to the results observed in the present study, which show a positive rate enhancement and percent conversion.
19. 2 through a 1150 mm (i.d.) capillary at a flow rate of 30 μL/min using the apparatus as shown in Figure 1.
20. Table 1, entry 6 was repeated using a 10% catalyst loading to afford 8 with 69% conversion together with 5% of 6 and 26% of benzaldehyde.
21. For discussion on palladium-catalyzed coupling reactions of aryl chlorides, see: Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41, 4176-4211.
22. Mayo, K. G.; Nearhoof, E. H.; Kiddle, J. J. Org. Lett. 2002, 4, 1567-1570.
23. Frattina, S.; Quai, M.; Cereda, E. Tetrahedron Lett. 2001, 42, 6827-6829.
24. Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc. 2001, 40, 9918-9919.
25. Gajewski, J. J.; Gee, K. R.; Jurayj, J. J. Org. Chem. 1990, 55, 1813-1822.
26. Available from Aldrich.
27. Tinnemans, A. H. A.; Laarhoven, W. H. J. Am. Chem. Soc. 1974, 96, 4611-4616.
28. Anderson, J. C.; Na mli, H.; Roberts, C. A. Tetrahedron 1997, 53, 15123-15134.
29. Miller, S. J.; Kim, S.-H.; Chen, Z.-R.; Grubbs, R. H. J. Am. Chem. Soc. 1995, 117, 2108-2109.
30. Organ, M. G.; Xu, J.; N'Zemba, B. M. Tetrahedron Lett. 2002, 43, 8177-8180.
31. Goetz, F. J.; Hirsch, J. A.; Augustine, R. L. J. Org. Chem. 1983, 48, 2468-2472.
32. Beaulieu, P. L.; Hache, B.; Von Moos, E. Synthesis 2003, 11, 1683-1692.
33. Zellner, H.; Zellner, G. Helv. Chim. Acta 1966, 49, 913-939.
34. Qian, C.; Wang, L. Tetrahedron 2000, 56, 7193-7197.