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Publisher: Georg Thieme Verlag
Languages: English
Types: Article
Subjects: QD0241
4-Aminopyridines undergo surprisingly rapid and highly-selective H/D exchange at C-2 and C-6 in neutral D2O upon microwave irradiation at only 190 °C for 2 h in a sealed vessel. This method contrasts and complements acid-mediated H/D exchange, requires no catalyst and is appropriate for the synthesis of deuterium isotop-ologues of N- and C-substituted 4-aminopyridines and a ben-zofused (quinoline) analogue.
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    • Junk, T.; Catallo, W. J. Chem. Soc. Rev. 1997, 26, 401.
    • Chem. Int. Ed. 2007, 46, 7744.
    • Blom, K.; Schuhardt, J.; Munson, B. Anal. Chem. 1985, 57, 1986.
    • Buteau, K. C. J. High Tech. L. 2009, 10, 22.
    • Hanson, J. R. In The Organic Chemistry of Isotopic Labelling, The Royal Society of Chemistry: Cambridge, 2011.
    • Thomas, A. F. In Deuterium Labeling in Organic Chemistry, Appleton-Century-Crofts Educational Div./Meredith Corp.: New York, 1972.
    • Murray III, A.; Williams, D. L. In Organic Synthesis with Isotopes. Part II: Organic Compounds Labeled with isotopes of the halogens, Hydrogen, Nitrogen, Oxygen, Phosphorus and Sulfur, Interscience Publishers, Inc.: New York, 1958.
    • Hvidt, A.; Nielsen, S. O. Adv. Protein Chem. 1966, 21, 287.
    • M.; Schriemer, D. C. Anal. Chim. Acta 2012, 721, 7; (b) Majumdar, R.; Middaugh, C. R.; Weis, D. D.; Volkin, D. B. J. Pharm. Sci. 2015, 104, 327.
    • (10) Lockley, W. J. S. J. Label. Compd. Radiopharm. 2007, 50, 256.
    • (11) Elander, N.; Jones, J. R.; Lu, S.-Y.; Stone-Elander, S. Chem. Soc. Rev. 2000, 29, 239.
    • (12) Garnett, J. L. Catal. Rev. 1971, 5, 229-267.
    • (13) Labinger, J. A.; Bercaw, J. E. Nature 2002, 417, 507.
    • (14) The area has been reviewed recently (references 2 and 5). Notable examples of acid-mediated methods, include: (a) Vaidyanathan, S.; Surber, B. W. Tetrahedron Lett. 2005, 46, 5195; (b) Fodor-Csorba, K.; Galli, G.; Holly, S.; GácsBaitz, E. Tetrahedron Lett. 2002, 43, 3789; (c) Boix, C.; Poliakoff, M. Tetrahedron Lett. 1999, 40, 4433; (d) Lockley, W. J. S. Tetrahedron Lett. 1982, 23, 3819. Notable examples of metal-mediated methods, include: (e) Sajiki, H.; Ito, N.; Esaki, H.; Maesawa, T.; Maegawa, T.; Hirota, K. Tetrahedron Lett. 2005, 46, 6995; (f) Derdau, V.; Atzrodt, J.; Zimmermann, J.; Kroll, C.; Brückner, F. Chem. Eur. J. 2009, 15, 10397; (g) Sajiki, H.; Aoki, F.; Esaki, H.; Maegawa, T.; Hirota, K. Org. Lett. 2004, 6, 1485; (h) Cioffi, E. A.; Bell, R. H.; Le, B. Tetrahedron Asymmetry 2005, 16, 471; (i) Cioffi, E. A. Tetrahedron Lett. 1996, 37, 6231; (j) Cioffi, E. A.; Alston, K. E.; Patel, A. M. Tetrahedron Lett. 2002, 43, 8985; (k) Sawama, Y.; Yamada, T.; Yabe, Y.; Morita, K.; Shibata, K.; Shigetsura, M.; Monguchi, Y.; Sajiki, H. Adv. Synth. Catal. 2013, 355, 1529; (l) Maegawa, T.; Fujiwara, Y.; Inagaki, Y.; Esaki, H.; Monguchi, Y.; Sajiki, H. Angew. Chem. Int. Ed. 2008, 47, 5394; (m) Derdau, V.; Atzrodt, J. Synlett 2006, 1918; (n) Hardacre, C.; Holbrey, J. D.; Jane McMath, S. E. Chem. Commun. 2001, 367.
    • (15) Edlund, U.; Bergson, G. Acta Chem. Scand. 1971, 25, 3625.
    • (16) Werstiuk, N. H.; Ju, C. Can. J. Chem. 1989, 67, 5.
    • (17) Junk, T.; Catallo, W. J. Tetrahedron Lett. 1996, 37, 3445.
    • (18) For Zoltewicz's original studies, see (a) Zoltewicz, J. A.; Smith, C. L. J. Am. Chem. Soc. 1967, 89, 3358; (b) Zoltewicz, J. A.; Kauffman, G. M.; Smith, C. L. J. Am. Chem. Soc. 1968, 90, 5939; (c) Zoltewicz, J. A.; Kauffman, G. M. J. Org. Chem 1969, 34, 1405; (d) Zoltewicz, J. A.; Helmick, L. S. J. Am. Chem. Soc. 1970, 92, 7547; (e) Zoltewicz, J. A.; Kandetzki, P. E. J. Am. Chem. Soc. 1971, 93, 6562.
    • (19) Kebede, N.; Pavlik, J. W. J. Heterocyclic Chem. 1997, 34, 685.
    • (20) Sullivan, J. A.; Flanagan, K. A.; Hain, H. Catal. Today 2008, 139, 154.
    • (21) Guy, K. A.; Shapley, J. R. Organometallics 2009, 28, 4020.
    • (22) Beringhelli, T.; Carlucci, L.; D'Alfonso, G.; Ciani, G.; Proserpio, D. M. J. Organomet. Chem. 1995, 504, 15.
    • (23) Prechtl, M. H. G.; Hölscher, M.; Ben-David, Y.; Theyssen, N.; Loschen, R.; Milstein, D.; Leitner, W. Angew. Chem. Int. Ed. 2007, 46, 2269.
    • (24) Eguillor, B.; Esteruelas, M. A.; García-Raboso, J.; Oliván, M.; Oñate, E. Organometallics 2009, 28, 3700.
    • (25) Piola, L.; Fernández-Salas, J.; Manzini, S.; Nolan, S. P. Org. Biomol. Chem. 2014, 12, 8683.
    • (26) McAuley, B.; Hickey, M. J.; Kingston, L. P.; Jones, J. R.; Lockley, W. J. S.; Mather, A. N.; Spink, E.; Thompson, S. P.; Wilkinson, D. J. J. Label. Compd. Radiopharm. 2003, 46, 1191.
    • (27) Esaki, H.; Ito, N.; Sakai, S.; Maegawa, T.; Monguchi, Y.; Sajiki, H. Tetrahedron 2006, 62, 10954.
    • (28) Alexakis, E.; Jones, J. R.; Lockley, W. J. S. Tetrahedron Lett. 2006, 47, 5025.
    • (29) General procedure for H/D exchange of 4- aminopyridines. A solution of the substrate in D2O (5 mL) was irradiated in a sealed Pyrex tube at 190 °C for 2 h (hold-time) using a CEM Explorer microwave synthesizer (maximum pressure 150 psi) by moderation of the initial microwave power (300 W). The mixture was cooled in a stream of compressed air and extracted with CH2Cl2 (3 × 10 mL). The organic extracts were combined, dried (MgSO4), filtered and evaporated in vacuo.
    • (30) (a) Barlin, G. B.; Pfleiderer, W. J. Chem. Soc. B 1971, 1425; (b) Collot, A.-G.; Courtney, M.; Coyne, D.; Eustace, S. E.; More O'Ferrall, R. A. J. Org. Chem. 2009, 74, 3356.
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