Synthesis, Table of Contents PAPER © Georg Thieme Verlag Stuttgart ˙ New York An Improved Preparation of 3-Alkoxypyrazoles Sandrine Guillou, Frédéric J. Bonhomme, Yves L. Janin*URA 2128 CNRS-Institut Pasteur, 28 rue du Dr. Roux, 75724 Paris cedex 15, FranceFax: +33(1)45688404.; e-Mail: yves.janin@pasteur.fr; Recommend Article Abstract Buy Article All articles of this category Abstract The condensation between alkyl acetoacetates and hydrazines constitutes the very well-known Knorr synthetic method leading to pyrazol-3/5-ones. However, contemporary reports describe an alternate reaction pathway leading to low yields of 3/5-alkoxypyrazoles using hydrazine salts. No general method for the selective synthesis of 3-alkoxypyrazoles has been reported to date, hence we focused on this side reaction in an attempt to turn it into the main transformation. Depending on the starting material, various 3-alkoxypyrazoles (methoxy, ethoxy, benzyloxy, isopropoxy, allyloxy) were obtained in up to 56% yield. Key words condensation - cyclizations - heterocycles - pyrazoles - Knorr reaction Full Text References References 1 Varvounis G. Fiamegos Y. Pilidis G. Adv. Heterocycl. Chem. 2001, 80: 74 2 Stanovik E. Svete J. In Science of Synthesis Vol. 12: Neier R. Georg Thieme Verlag; Stuttgart: 2002. p.15 3 Knorr L. Ber. Dtsch. Chem. Ges. 1895, 28: 706 4 Stolz F. Ber. Dtsch. Chem. Ges. 1895, 28: 635 5 Wolff L. Ber. Dtsch. Chem. Ges. 1904, 37: 2827 6 Backer HJ. Meijer W. Recl. Trav. Chim. Pays-Bas 1926, 45: 428 7 Maquestiau A. Van Haverbeke Y. Bruyere A. Bull. Soc. Chim. Belg. 1973, 82: 747 8 Arakawa K. Miyasaka T. Ochi H. Chem. Pharm. Bull. 1974, 22: 207 9 Puar MS. Funke PT. Cohen AI. J. Pharm. Sci. 1978, 67: 850 10 Pilgram K. J. Heterocycl. Chem. 1980, 17: 1413 11 Zefirov NS. Kozhushkov SI. Kuznetsova TS. Khim. Geterotsikl. Soedin. 1983, 19: 801 12 Krohn K. Stenns C. Arch. Pharm. (Weinheim, Ger.) 1989, 322: 351 13 Claramunt RM. Sanz D. Lopez C. Jimenez JA. Jimeno ML. Elguero J. Fruchier A. Magn. Res. Chem. 1997, 35: 35 14 Batterjee SM. J. Text. Assoc. 2001, 62: 145 15 Martins MAP. Pereira CMP. Zimmermann NEK. Moura S. Sinhorin AP. Cunico W. Zanatta N. Bonacorso HG. Flores ACF. Synthesis 2003, 2353 16 Bevk D. Svete J. Stanovnik B. J. Heterocycl. Chem. 2005, 42: 1413 17 Bau B. Hofmann T. Kloss J. Neunhoeffer H. Sci. Pharm. 1998, 66: 119 18 Selwood DL. Brummell DG. Budworth J. Burtin GE. Campbell RO. Chana SS. Charles IG. Fernandez PA. Glen RC. Goggin MC. Hobbs AJ. Kling MR. Liu Q. Madge DJ. Millerais S. Powell KL. Reynolds K. Spacey GD. Stables JN. Tatlock MA. Wheeler KA. Wishart G. Woo C.-K. J. Med. Chem. 2001, 44: 78 19 Zimmermann D. Janin YL. Brehm L. Bräuner-Osborne H. Ebert B. Johansen TN. Madsen U. Krogsgaard-Larsen P. Eur. J. Med. Chem. 1999, 34: 967 20 Janin YL. Huel C. Flad G. Thirot S. Eur. J. Org. Chem. 2002, 1763 21 Genevois Borella A. Malleron JL. Bouquerel J. Doerflinger G. Bohme A. Touyer G. Sabuco JF. Terrier C. Mignani S. Evers M. FR 2,862,647 Chem. Abstr. 2005, 143: 7705p 22 Cottineau B. Toto P. Marot C. Pipaud A. Chenault J. Bioorg. Med. Chem. Lett. 2002, 12: 2105 23 Willson TS. Henke BR. Momtahen TM. Garrison DT. Moore LB. Geddie NG. Baer PG. Bioorg. Med. Chem. Lett. 1996, 6: 1047 24 Rossiter S. Woo CK. Hartzoulakis B. Wishart G. Stanyer L. Labadie JW. Selwood DL. J. Comb. Chem. 2004, 6: 385 25 Braibante MEF. Braibante HTS. de Carvalho Tavares L. Rohte SF. Costa CC. Morel AF. Stüker CZ. Burrow RA. Synthesis 2007, 2485 26 Khalil AK. Hassan MA. Mohamed MM. El-Sayed AM. Phosphorus, Sulfur Silicon Relat. Elem. 2005, 180: 479 27 Grünanger P. Vita-Finzi P. In The Chemistry of Heterocyclic Compounds Vol. 49: Taylor EC. John Wiley & Sons; Chichester: 1991. 28 v Auwers K. Niemeyer F. J. Prakt. Chem. 1925, 110: 153 29 Singh G. Singh D. Ram RN. Tetrahedron Lett. 1981, 22: 2213 30 Ohta T. Fujisawa H. Nakai Y. Furukawa I. Bull. Chem. Soc. Jpn. 2000, 73: 1861 31 Rodríguez-Franco MI. Dorronsoro I. Hernández-Higueras AI. Antequera G. Tetrahedron Lett. 2001, 42: 863 32 Martins MAP. Cunico W. Brondani S. Peres RL. Zimmermann N. Rosa FA. Fiss GF. Zanatta N. Bonacorso HG. Synthesis 2006, 1485