Continuous Flow Techniques in Organic Synthesis

Chemistry - A European Journal

Volumn 9, Issue 23, 2003, Pages 5708-5723

  Jas, Gerhard ^a   Kirschning, Andreas ^b  

^a CHELONA GmbH   (Germany)

^b LEIBNIZ UNIVERSITY HANNOVER   (Germany)

Author keywords

Automated synthesis; Combinatorial chemistry; Flow through processes; Monolithic materials; Polymers; Reactors

Indexed keywords

AUTOMATION; CHEMICAL REACTORS; DRUG PRODUCTS; RESEARCH LABORATORIES; SYNTHESIS (CHEMICAL);

CONTINUOUS FLOW PROCESSES; MICROREACTORS;

ORGANIC COMPOUNDS;

POLYMER; REAGENT;

ADAPTATION; AUTOMATION; CATALYST; CHEMICAL ENGINEERING; CHEMICAL STRUCTURE; COMBINATORIAL CHEMISTRY; CONTINUOUS FLOW REACTOR; COOPERATION; KINETICS; MATERIALS; ORGANIC CHEMISTRY; PARAMETER; REACTION ANALYSIS; RELIABILITY; REPRODUCIBILITY; RESEARCH; REVIEW; SAFETY; SOLID; SYNTHESIS; TECHNOLOGY; THERMODYNAMICS;

EID: 0345732180     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200305212     Document Type: Review

References (132)

1. a) F.Z. Dörwald, Organic Synthesis On Solid Support, Willey VCH, Weinheim 2000;
2. b) N. K. Terrett, Combinatorial Chemistry, Oxford University Press 1998;
3. c) D. Obrecht, J. M. Villalgordo, Solid-Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries, Pergamon, Elsevier Science, Oxford, 1998;
4. d) S. R. Wilson, A. W. Czarnik, Combinatorial Chemistry, Synthesis, Application, Wiley, New York 1997;
5. e) "Matrix Assisted Synthetic Transformations: A Mosaic of Diverse Contributions": D. Hudson, J. Comb. Chem. 1999, 1, 333-360 and D. Hudson, J. Comb. Chem. 1999, 1, 403-456;
6. e) "Matrix Assisted Synthetic Transformations: A Mosaic of Diverse Contributions": D. Hudson, J. Comb. Chem. 1999, 1, 333-360 and D. Hudson, J. Comb. Chem. 1999, 1, 403-456;
7. f) D. E. Bergbreiter, Med. Res. Rev. 1999, 19, 439-450;
8. g) S. F. Oliver, C. Abell, Curr. Opin. Chem. Biol. 1999, 3, 299-306;
9. h) J. S. Früchtel, G. Jung, Angew. Chem. 1996, 108, 19-46; Angew. Chem. Int. Ed. Engl. 1996, 35, 17-42;
10. h) J. S. Früchtel, G. Jung, Angew. Chem. 1996, 108, 19-46; Angew. Chem. Int. Ed. Engl. 1996, 35, 17-42;
11. i) F. Balkenhol, C. von dem Bussche-Hünnefeld, A. Lansky, C. Zechel, Angew. Chem. 1996, 108, 2437-2488; Angew. Chem. Int. Ed. Engl. 1996, 35, 2288-2337;
12. i) F. Balkenhol, C. von dem Bussche-Hünnefeld, A. Lansky, C. Zechel, Angew. Chem. 1996, 108, 2437-2488; Angew. Chem. Int. Ed. Engl. 1996, 35, 2288-2337;
13. j) L. A. Thompson, J. A. Ellman, Chem. Rev. 1996, 96, 555-600;
14. k) S. V. Ley, I. R. Baxendale, Nat. Rev. Drug Discovery 2002, 1, 573-586.
15. Recent reviews on polymer-supported reagents: a) A. Kirschning, H. Monenschein, R. Wittenberg, Angew. Chem. 2001, 113, 670-701; Angew. Chem. Int. Ed. 2001, 40, 650-679;
16. Recent reviews on polymer-supported reagents: a) A. Kirschning, H. Monenschein, R. Wittenberg, Angew. Chem. 2001, 113, 670-701; Angew. Chem. Int. Ed. 2001, 40, 650-679;
17. b) S. V. Ley, I. R. Baxendale, R. N. Bream, P. S. Jackson, A. G. Leach, D. A. Longbottom, M. Nesi, J. S. Scott, R. I. Storer, S. J. Taylor, J. Chem. Soc. Perkin Trans. 1 2000, 3815-4195 (particularly see p. 3832);
18. c) D. H. Drewry, D. M. Coe, S. Poon, Med. Res. Rev. 1999, 19, 97-148;
19. d) S. V. Ley, I. R. Baxendale, Nat. Rev. Drug Discovery 2002, 1, 575-586.
20. O.J. Plante, E. R. Palmacci, P. H. Seeberger, Science 2001, 291, 1523-1527.
21. "Life During a Golden Age of Peptide Chemistry": B. Merrifield in Profiles, Pathways and Dreams: Autobiographies of Eminent Chemists (Ed.: J.I. Seeman), American Chemical Society, Washington, DC, 1993.
22. a) E. Atherton, E. Brown, R. C. Sheppard, A. Rosevear, J. Chem. Soc. Chem. Commun. 1981, 1151-1152;
23. b) A. Dryland, R. C. Sheppard, J. Chem. Soc. Perkin Trans. 1 1986, 125-137.
24. E. Atherton, Pept. Proc. Eur. Pept. Symp. 17th Berlin, 1983, 241.
25. A fully automated machine was developed and commercialized by Pharmacia-LKB, Cambridge Research Biochemical, MilliGen, duPont and applied Biosystems. See also E. Atherton, R. C. Sheppard, Solid Phase Peptide Synthesis, IRL Press, Oxford, 1989, p. 100; a flow-through concept based on membranes incorporated into a cartridge was disclosed by S. B. Daniels, M. S. Bernatowicz, J. M. Coull, H. Köster, Tetrahedron Lett. 1989, 30, 4345-4348.
26. A fully automated machine was developed and commercialized by Pharmacia-LKB, Cambridge Research Biochemical, MilliGen, duPont and applied Biosystems. See also E. Atherton, R. C. Sheppard, Solid Phase Peptide Synthesis, IRL Press, Oxford, 1989, p. 100; a flow-through concept based on membranes incorporated into a cartridge was disclosed by S. B. Daniels, M. S. Bernatowicz, J. M. Coull, H. Köster, Tetrahedron Lett. 1989, 30, 4345-4348.
27. F Mutulis, M. Tysk, I. Mutule, J. E. S. Wikberg, J. Comb. Chem. 2003, 5, 1-7.
28. R. Frank, R. Doering, Tetrahedron 1988, 44, 6031-6040.
29. E. Angelletti, C. Canepa, G. Martinetti, P. Venturello, Tetrahedron Lett. 1988, 29, 2261.
30. E. Angelletti, C. Canepa, G. Martinetti, P. Venturello, J. Chem. Soc. Perkin Trans. 1 1989, 105-107.
31. a) Microreaction Technology, (Ed.: W. Ehrfeld), Springer, Berlin, 1998;
32. b) W. Ehrfeld, V. Hessel, H. Löwe, Microreactors, Wiley-VCH, Weinheim, 2000;
33. c) Microsystem Technology in Chemistry and Life Sciences, (Eds.: A. Manz, H. Becker) Springer, Berlin, 1999.
34. R. M. Heck, S. Gulati, R. J. Farrauto, Chem. Eng. J. 2001, 82, 149-156.
35. L. Kiwi-Minsker, Chimia 2002, 56, 143-147.
36. a) F. Svec, J. M. J. Fréchet, Anal. Chem. 1992, 64, 820-822;
37. b) C. Viklund, F. Svec, J. M. J. Fréchet, K. Ignum, Chem. Mater. 1996, 8, 744-750;
38. c) E. C. Peters, F. Svec, J. M. J. Fréchet, Adv. Mater 1999, 11, 1169-1181;
39. d) N. Hird, I. Hughes, D. Hunter, M. G. J. T. Morrison, D. C. Sherrington, L. Stevenson, Tetrahedron 1999, 55, 9575-9584;
40. e) J. A. Tripp, J. A. Stein, F. Svek, J. M. J. Fréchet, Org. Lett. 2000, 2, 195-198;
41. f) J. A. Tripp, F. Svec, J. M. J. Fréchet, J. Comb. Chem. 2001, 3, 216-223.
42. 2 can also serve as a porogen for the preparation of porous monolithic materials: A. K. Hebb, K. Senoo, R. Bhat, A. I. Cooper, Chem. Mater. 2003, 15, 2061-2069.
43. B. Altava, M. I. Burguete, J. M. Fraile, J. I. García, S. V. Luis, J. A. Mayoral, M.J. Vincent, Angew. Chem. 2000, 112, 1563-1566; Angew. Chem. Int. Ed. 2000, 39, 1503-1506.
44. B. Altava, M. I. Burguete, J. M. Fraile, J. I. García, S. V. Luis, J. A. Mayoral, M.J. Vincent, Angew. Chem. 2000, 112, 1563-1566; Angew. Chem. Int. Ed. 2000, 39, 1503-1506.
45. a) F. Svec, J.M.J. Fréchet, Chem. Mater. 1995, 7, 707-715;
46. b) F. Svec, J. M. J. Fréchet, Science 1996, 273, 205-211.
47. T. B. Tennikova, B. G. Belenkii, F. Svec, J. Liq. Chromatogr. 1990, 13, 63-70.
48. D. Josic, A. Buchacher, A. Jungbauer, J. Chromatogr. B 2001, 752, 191-205.
49. H. Abou-Rebyeh, F. Korber, K. Schubert-Rehberg, J. Reusch, D. Josic, Anal. Chim. Acta 2000, 407, 105-110;
50. b) R. Hahn, A. Jungbauer, Anal. Chem. 2000, 72, 4853-4858.
51. K. Pflegerl, A. Podgomik, E. Berger, A. Jungbauer, J. Comb. Chem. 2002, 4, 33-37 and references therein.
52. a) M. R. Buchmeiser, Angew. Chem. 2001, 113, 3911-3913; Angew. Chem. Int. Ed 2001, 40, 3795-3797;
53. a) M. R. Buchmeiser, Angew. Chem. 2001, 113, 3911-3913; Angew. Chem. Int. Ed 2001, 40, 3795-3797;
54. b) M. Mayr, B. Mayr, M. R. Buchmeiser, Angew. Chem. 2001, 113, 3957-3960; Angew. Chem. Int. Ed. 2001, 40, 3839-3842;
55. b) M. Mayr, B. Mayr, M. R. Buchmeiser, Angew. Chem. 2001, 113, 3957-3960; Angew. Chem. Int. Ed. 2001, 40, 3839-3842;
56. c) F. Sinner, M. R. Buchmeiser, Macromolecules 2000, 33, 5777-5786;
57. d) F. Sinner, M. R. Buchmeiser, Angew. Chem. 2000, 112, 1491-1494; Angew. Chem. Int. Ed. 2000, 39, 1433-1436.
58. d) F. Sinner, M. R. Buchmeiser, Angew. Chem. 2000, 112, 1491-1494; Angew. Chem. Int. Ed. 2000, 39, 1433-1436.
59. a. S. Zalusky, R. Olayo-Valles, C. J. Taylor, M. A. Hillmyer, J. Am. Chem. Soc. 2001, 123, 1519-1520.
60. A. Kirschning, C. Altwicker, G. Dräger, J. Harders, N. Hoffmann, U. Hoffmann, H. Schönfeld, W. Solodenko, U. Kunz, Angew. Chem. 2001, 113, 4118-4120; Angew. Chem. Int. Ed. 2001, 40, 3995-3998.
61. A. Kirschning, C. Altwicker, G. Dräger, J. Harders, N. Hoffmann, U. Hoffmann, H. Schönfeld, W. Solodenko, U. Kunz, Angew. Chem. 2001, 113, 4118-4120; Angew. Chem. Int. Ed. 2001, 40, 3995-3998.
62. K. Sundmacher, H. Künne, U. Kunz, Chem. Ing. Tech. 1998, 70, 267-271.
63. a) H. Yang, Q. Shi, X. Liu, S. Xie, D. Jiang, E Zhang, C. Yu, B. Tu, D. Zhao, Chem. Commun. 2002, 2842-2843;
64. b) C. Liang, S. Dai, G. Guiochon, Chem. Commun. 2002, 2680-2681 and references therein.
65. K. Ishihara, A. Hasegawa, H. Yamamoto, Synlett 2002, 1296-1298.
66. a) S. Itsuno, A. Hirao, S. Nakahuma, Makromol. Chem. Rapid Commun. 1982, 3, 673.
67. a) S. Itsuno, M. Nakano, K. Miyazaki, H. Masuda, K. Ito, A. Hirao, S. Nakahama, J. Chem. Soc. Perkin Trans. 1 1985, 2039-2044;
68. b) S. Itsuno, M. Nakano, K. Ito, A. Hirao, M. Owa, N. Kanda, S. Nakahama, J. Chem. Soc. Perkin Trans. 1 1985, 2615-2619;
69. c) S. Itsuno, K. Ito, T. Maruyaima, N. Kanda, A. Hirao, S. Nakahama, Bull. Chem. Soc. Jpn. 1986, 59, 3329-3331;
70. d) S. Itsuno, Y. Sakurai, K. Ito, A. Hirao, S. Nakahama, Bull. Chem. Soc. Jpn. 1987, 60, 395-396.
71. S. Itsuno, Y. Sakurai, K. Ito, T. Maruyama, S. Nakahama, J. M. J. Fréchet, J. Org. Chem. 1990, 55, 304-310.
72. P. Hodge, D. W. L. Sung, P. W. Stratford, J. Chem. Soc. Perkin Trans. 1 1999, 2335-2342.
73. M. I. Burgurette, E. Garcia-Verdugo, M. J. Vicent, S. V. Luis, H. Pennemann, N. Graf von Keyserling, J. Martens, Org. Lett. 2002, 4, 3947-3950.
74. F. Svec, J. M. J. Fréchet, Science 1996, 273, 205-211 and reference [15].
75. D. A. Annis, E. N. Jacobsen, J. Am. Chem. Soc. 1999, 121, 4147-4154.
76. A. J. Sandee, D.G.I. Petra, J. N. H. Reek, P. C. J. Kramer, P. W. N. M. van Leeuwen, Chem. Eur. J. 2001, 7, 1202-1208.
77. For a review refer to: A. Liese, K. Seelbach, C. Wandrey, Industrial Biotransformations, Wiley VCH, 2000.
78. P. Chen, S. Han, G. Lin, Z. Li, J. Org. Chem. 2002, 67, 8251-8253.
79. a) Z. Liu, J. Zhang, C. Chen, P. G. Wang, ChemBioChem 2002, 3, 348-355;
80. b) J. Nahalka, Z. Liu, X. Chen, P. G. Wang, Chem. Eur. J. 2003, 9, 373-377.
81. a) G. Sourkouni-Argirusi, A. Kirschning, Org. Lett. 2000, 2, 3781-3784;
82. b) M. Brünjes, G. Sourkouni-Argirusi, A. Kirschning, Adv. Synth. Catal. 2003, 345, 635-642.
83. a) U. Kunz, H. Schönfeld, A. Kirschning, W. Solodenko, J. Chromatogr. A 2003, 1006,241-249;
84. b) W. Solodenko, U. Kunz, A. Kirschning, Bioorg. Med. Chem. Lett. 2002, 12, 1833-1835.
85. a) S. Kotha, K. Lahiri, D. Kashinat, Tetrahedron 2002, 58, 9633-9695;
86. b) A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350-4386; Angew. Chem. Int. Ed. 2002, 41, 4176-4211.
87. b) A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350-4386; Angew. Chem. Int. Ed. 2002, 41, 4176-4211.
88. V. Lobregat, G. Alcaraz, H. Bienayme, M. Vaultier, Chem. Commun. 2001, 817-818.
89. W. Solodenko, G. Jas, U. Kunz, A. Kirschning unpublished results.
90. M. E. Furrow, S. E. Schaus, E. N. Jacobsen, J. Org. Chem. 1998, 63, 6776-6777.
91. -1), respectively, across a length of about 10 cm.
92. A. M. Hafez, A. E. Taggi, T. Lectka, Chem. Eur. J. 2002, 8, 4114-4119.
93. a) A. M. Hafez, A. E. Taggi, T. Dudding, T. Lectka, J. Am. Chem. Soc. 2001, 123, 10853-10859;
94. b) A.M. Hafez, A. E. Taggi, H. Wack, W. J. Drury III, T. Lectka, Org. Lett. 2000, 2, 3963-3965.
95. R. Giguere, Mater. Res. Soc. Symp. Proc. 1992, 269, 387; original paper published in R. J. Guigerre, T. L. Bray, S. N. Duncan, G. Majetich, Tetrahedron Lett. 1986, 27 28, 4945-4948.
96. R. Giguere, Mater. Res. Soc. Symp. Proc. 1992, 269, 387; original paper published in R. J. Guigerre, T. L. Bray, S. N. Duncan, G. Majetich, Tetrahedron Lett. 1986, 27 28, 4945-4948.
97. Selected reviews: a) H. E. Blackwell, Org. Biomol. Chem. 2003, 1, 1251-1255;
98. b) M. Larhed, C. Moberg, A. Hallberg, Acc. Chem. Res. 2002, 35, 717-727;
99. c) B. Wathey, J. Tierney, P. Lidström, J. Westman, Drug Discovery Today 2002, 7, 373-380;
100. d) A. Lew, P. O. Krutzik, M. E. Hart, A.R. Chamberlin, J. Comb. Chem. 2002, 4, 95-105;
101. e) P. Lidström, J. Tierney, B. Wathey, J. Westman, Tetrahedron 2001, 57, 9225-9283.
102. a) C. R. Strauss, A. F. Faux, International Patent Application PCT/AU89/00437, 1989;
103. b) T. Cablewski, A. F. Faux, C. R. Strauss, J. Org. Chem. 1994, 59, 3408-3412 and references therein.
104. a) C. O. Kappe, Am. Lab. 2001, 33, 13-19;
105. b) C. O. Kappe, Curr. Opin. Chem. Biol. 2002, 6, 314-320 and references therein.
106. G. Sourkouni-Argirusi, S. Leue, A. Kirschning, G. Jas, unpublished results.
107. M. T. Reetz, W. Wiesenhöfer, G. Franciò, W. Leitner, Chem. Commun. 2002, 992-993.
108. I. F. J. Vankelecom, Chem. Rev. 2002, 102, 10, 3779-3810.
109. a) H. P. Dijkstra, N. Ronde, G. P. M. Van Klink, D. Vogt, G. Van Koten, Adv. Synth. Catal. 2003, 345, 364-369.
110. b) R. Sablong, U. Schlotterbeck, D. Vogt, S. Mecking, Adv. Synth. Catal. 2003, 345, 333-335.
111. a) K. De Smet, S. Aets, E. Ceulemans, I. F. J. Vankelecom, P. A. Jacobs, Chem. Commun. 2001, 7, 597-598;
112. b) K. De Smet, A. Pleysier, I. F. J. Vankelecom, P. A. Jacobs, Chem. Eur. J. 2003, 9, 334-338.
113. Review: P. D. I. Fletcher, S. J. Haswell, E. Pombo-Villar, B. H. Warrington, P. Watts, S. Y. F. Wong, X. Zhang, Tetrahedron 2002, 58, 4735-4757.
114. a) S. H. DeWitt, Curr. Opin. Chem. Biol. 1999, 3, 350-356;
115. b) H. Okamoto, Yuki Gosei Kagaku Kyokaishi 1999, 57, 805-812;
116. c) T. Sugawara, Pharmacia 2000, 36, 34.
117. a) P. D. I. Fletcher, S. J. Haswell, V. N. Paunov, B. H. Warrington, P. Watts, S. Y. F. Wong, X. Zhang, Tetrahedron 2002, 58, 4735-4757;
118. b) S. J. Haswell, R. J. Middleton, B. O'Sullivan, V. Skelton, P. Watts, P. Styring, Chem. Commun. 2001, 391-398;
119. c) P. D. I. Fletcher, S. J. Haswell, V. N. Paunov, Analyst 1999, 124, 1273-1282.
120. B. Wiles, P. Watts, S. J. Haswell, E. Pombo-Villar, Chem. Commun. 2002, 1034-1045.
121. P. Watts, C. Wiles, S. J. Haswell, E. Pombo-Villar, Tetrahedron 2002, 58, 5427-5439.
122. P. Watts, C. Wiles, S. J. Haswell, E. Pombo-Villar, P. Styring, Chem. Commun. 2001, 990-991.
123. V. Skelton, G. M. Greenway, S. J. Haswell, P. Styring, D. O. Morgan, B. Warrington, S. Y. F. Wong, Analyst 2001, 126, 7-10.
124. T. Fukuyama, M. Shinmen, S. Nishitani, M. Sato, I. Ryu, Org. Lett. 2002, 4, 1691-1694.
125. Recent examples of synthesis using microflow systems: a) H. Salimi-Moosavi, T. Tang, D. J. Harrison, J. Am. Chem. Soc. 1997, 119, 8716-8717;
126. b) R. D. Chambers, R. C. H. Spink, Chem. Commun. 1999, 883-884.
127. Micromixers with channels width of 40 μm and depth of 200 μm have been developed at the Institut für Mikrotechnik Mainz GmbH (IMM).
128. S. Suga, M. Okajima, K. Fujiwara, J. Yoshida, J. Am. Chem. Soc. 2001, 123, 7941-7942 and references therein.
129. H. Löwe, W. Ehrfeld, Electrochim. Acta 1999, 44, 3679-3689.
130. C. Karakus, P. Zuman, J. Electrochem. Soc. 1995, 142, 4018.
131. C. Bellefon, N. Tanchoux, S. Caravieilhes, P. Grenouillet, V. Hessel, Angew. Chem. 2000, 112, 3584-3587; Angew. Chem. Int. Ed. 2000, 39, 3442-3445.
132. C. Bellefon, N. Tanchoux, S. Caravieilhes, P. Grenouillet, V. Hessel, Angew. Chem. 2000, 112, 3584-3587; Angew. Chem. Int. Ed. 2000, 39, 3442-3445.