The continuous-flow synthesis of ibuprofen

Angewandte Chemie - International Edition

Volumn 48, Issue 45, 2009, Pages 8547-8550

  Bogdan, Andrew R ^b   Poe, Sarah L ^b   Kubis, Daniel C ^b   Broadwater, Steven J ^b   McQuade, D Tyler ^a  

^a FLORIDA STATE UNIVERSITY   (United States)

^b Department of Obstetrics Gynecology   (United States)

Author keywords

Continuous processing; Flow chemistry; Microreactors; Reactor design; Synthetic methods

Indexed keywords

CONTINUOUS PROCESSING; FLOW CHEMISTRY; MICROREACTORS; REACTOR DESIGN; SYNTHETIC METHODS;

CHEMICAL REACTORS;

SUGAR (SUCROSE);

EID: 70350348246     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200903055     Document Type: Article

References (54)

1. R. A. Sheldon, J. Chem. Technol. Biotechnol. 1997, 68, 381.
2. P. J. Anastas, M. M. Kirchhoff, Acc. Chem. Res 2002, 35, 686.
3. B. P. Mason, K. E. Price, J. L. Steinbacher, A. R. Bogdan, D. J. McQuade, Chem. Rev. 2007, 107, 23(K).
4. V. Hessel, P. Lob, H. Löwe, Curr. Org. Chem. 2005, 9, 765.
5. V Hessel, H. Löwe, Chem. Eng. Technol. 2005, 25, 267.
6. P. Hodge, Curr. Opin. Chem. Biol. 2003, 7, 362.
7. G. Jas, A. Kirschning, Chem Eur. J. 2003, 9, 5708.
8. A. Kirschning, H. Monenschein, R. Wittenberg, Angew. Chem. 2001, 113, 670;
9. Angew. Chem. Int. Ed. 2001, 40, 650.
10. H. Pennemann, P. Watts, S. J. Haswell, V. Hessel, H. Löwe, Org. Process Res. Dev. 2004, 8, 422.
11. Microreactors in Organic Synthesis and Catalysis (Ed. : J. Wirth), Wiley-VCH, Weinheim, 2008.
12. P. Watts, C. Wiles, Org. Biomol. Chem. 2007, 5, 727.
13. J. Fukuyama, M. J. Rahman, M. Sato, I. Ryu, Synlett 2008, 151.
14. B. Ahmed-Omer, J. C. Brandt, J. Wirth, Org. Biomol. Chem. 2007, 5, 733.
15. M. J. Reetz, W. Wiesenhofer, G. Francio, W. Leitner, Adv. Synth. Catal. 2003, 345, 1221.
16. C. Wiles, P. Watts, S. J. Haswell, E. Pombo-Villar, Tetrahedron 2003, 59, 10173.
17. P. W. Miller, N. J. Long, A. J. Mello, R. Vilar, J. Passchier, A. Gee, Chem. Commun. 2006, 546.
18. G. Shore, S. Morin, M. G. Organ, Angew. Chem. 2006, 118, 2827;
19. Angew. Chem. Int. Ed. 2006, 45, 2761.
20. F. Bonfils, I. Cazaux, P. Hodge, C. Caze, Org. Biomol. Chem. 2006, 4, 493.
21. I. R. Baxendale, C. H. Griffiths-Jones, S. V. Ley, G. K. Xranmer, Chem. Eur. J. 2006, 12, 4407.
22. J. Yoshida, A. Nagaki, J. Yamada, Chem. Eur. J. 2008, 74, 7450, and references therein.
23. A. Nagaki, N. Takabayashi, Y. Tomida, J. Yoshida, Org. Lett. 2008, 10, 3937.
24. A. Nagaki, H. Kim, J. Yoshida, Angew. Chem. 2008, 120, 7951;
25. Angew. Chem. Int. Ed. 2008, 47, 7833.
26. J. M. J. van der Linden, P. W. Hilberink, C. M. P. Kronenburg, G. J. Kemperman, Org. Process Res. Dev. 2008, 12, 911.
27. A. R. Bogdan, N. W. Sach, Adv. Synth. Catal. 2009, 351, 849.
28. W. Ehrfeld, V. Hessel, H. Lowe, Microreactors: New Technology for Modern Chemistry, Wiley-VCH, Weinheim, 2000.
29. C. H. Hornung, M. R. Mackley, I. R. Baxendale, S. V. Ley, Org. Process Res. Dev. 2007, 11, 399.
30. D. R. J. Acke, C. V. Stevens, Org. Process Res Dev. 2006, 10, 417.
31. H. R. Sahoo, J. G. Kralj, K. F. Jensen, Angew. Chem. 2007, 119, 5806;
32. Angew. Chem. Int. Ed. 2007, 46, 5704.
33. I. R. Baxendale, J. Deeley, C. M. Griffiths-Jones, S. V Ley, S. Saaby, G. K. Tranmer, Chem. Commun. 2006, 2566.
34. I. R. Baxendale, S. V Ley, A. C. Mansfield, C. D. Smith, Angew. Chem. 2009, 121, 4077;
35. Angew. Chem. Int. Ed. 2009, 45, 4017.
36. I. R. Baxendale, C. H. Griffiths-Jones, S. V. Ley, G. K. Tranmer, Synlett 2006, 42.
37. D. Grant, R. Dahl, N. D. P. Cosford, J. Org. Chem. 2008, 73, 7219.
38. A. R. Bogdan, B. P. Mason, K. J. Sylvester, D. J. McQuade, Angew. Chem. 2007, 119, 1728;
39. Angew. Chem. Int. Ed. 2007, 46, 1698.
40. A. R. Bogdan, D. J. McQuade, Beilstein J. Org. Chem. 2009, 5, 17.
41. S. L. Poe, M. Kobašlija, D. J. McQuade, J. Am. Chem. Soc. 2006, 128, 15586.
42. S. L. Poe, M. Kobašlija, D J. McQuade, J. Am. Chem. Soc. 2007, 129, 9216.
43. Y Xamura, J. Yakura, Y. Shirouchi, J. Haruta, Chem. Pharm. Bull. 1985, 5, 1097.
44. R. M. G. Roberts, A. R. Sadri, Tetrahedron 1983, 39, 137.
45. F. Effenberger, G. Epple, Angew. Chem. 1972, 54, 295;
46. Angew. Chem. Int. Ed. Engl. 1972, 11, 300.
47. It is proposed that the reaction of triflic acid with propionic acid leads to the generation of a protonated mixed anhydride, a very active acylating agent.
48. In our flow reactor, the use of PFA tubing and unions was critical to withstand the caustic nature of TfOH. For a detailed description of the materials used, see the Supporting Information.
49. Similar yields were obtained when the Friedel - Crafts acylation was performed in batch, at 150°C.
50. O. V. Singh, O. Prakash, C. P. Garg, R. P. Kapoor, Ind. J. Org. Chem. 1989, 28B, 814.
51. O. Prakash, S. Goyal, R. M. Moriarty, J. S. Khosrowshahi, Ind. J. Org. Chem. 1990, 289B, 304.
52. It was found to be necessary to cool, the tee junction owing to significant off-gassing that occurred when it was held at room temperature. This off-gassing did not occur during the optimization and therefore this tee junction did not need to be cooled.
53. Iodobenzene is the byproduct of the 1,2-aryl migration, It can be converted back to PhI(OAc)2 by treatment with, peracetic acid.
54. The low yield from the recrystallization of ibuprofen is most likely a consequence of the small scale. The recrystallizations of larger batches of ibuprofen gave higher yields.