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DOI: 10.1055/s-2006-950258
Unexpected Ring Closure between Hydrazono and Nitro Groups: A Useful Synthesis of Substituted Pyrazole N-Oxides
Publication History
Publication Date:
09 October 2006 (online)
Abstract
An efficient protocol for the construction of pyrazole N-oxides is reported. This occurs by cyclization of β-nitrohydrazone derivatives obtained from the reaction between 1,2-diaza-1,3-butadienes and nitroalkanes under solvent-free conditions.
Key words
Michael additions - nitro compounds - 1,2-diaza-1,3-butadienes - hydrazones - pyrazole N-oxides
-
1a
Ono N. The Nitro Group in Organic Synthesis John Wiley; New York: 2001. -
1b
Adams JP. J. Chem. Soc., Perkin Trans. 1 2002, 2586 -
1c
Gissot A.N’Gouela S.Matt C.Wagner A.Mioskowski C. J. Org. Chem. 2004, 69: 8997 -
1d
Ballini R.Bosica G.Fiorini D.Palmieri A. Tetrahedron 2005, 61: 8971 - 2
Krawczyk H.Wolf WM.Sliwinski M. J. Chem. Soc., Perkin Trans. 1 2002, 2794 - 3
Trost BM.Yeh VSC.Ito H.Bremeyer N. Org. Lett. 2002, 4: 2621 - 4
Carey FA.Sundberg RJ. In Advanced Organic Chemistry, Part B 4th ed.: Plenum; New York: 2001. p.100-101 -
5a
Attanasi OA.Filippone P.Mei A.Santeusanio S. Synthesis 1984, 671 -
5b
Attanasi OA.Filippone P.Mei A.Santeusanio S. Synthesis 1984, 873 -
5c
Attanasi OA.Caglioti L. Org. Prep. Proced. Int. 1986, 18: 299 -
5d
Attanasi OA.Filippone P. Synlett 1997, 1128 -
5e
Attanasi OA.De Crescentini L.Filippone P.Mantellini F.Santeusanio S. ARKIVOC 2002, (xi): 274 ; and references cited therein -
5f
Attanasi OA.Baccolini G.Boga C.De Crescentini L.Filippone P.Mantellini F. J. Org. Chem. 2005, 70: 4033 -
5g
Attanasi OA.De Crescentini L.Favi G.Filippone P.Lillini S.Mantellini F.Santeusanio S. Org. Lett. 2005, 7: 2469 -
6a
Freeman JP.Gannon JJ.Surbey DL. J. Org. Chem. 1969, 34: 187 -
6b
Vedsø P.Begtrup M. J. Chem. Soc., Perkin Trans. 1 1995, 243 -
6c
Alcazar J.Almena I.Begtrup M.de la Hoz A. J. Chem. Soc., Perkin Trans. 1 1995, 2773 -
6d
Eskildsen J.Kristensen J.Vedsø P.Begtrup M. J. Org. Chem. 2001, 66: 8654 -
6e
Paulson AS.Eskildsen J.Vedsø P.Begtrup M. J. Org. Chem. 2002, 67: 3904 -
6f
Østergaard N.Skjærbæk N.Begtrup M.Vedsø P. J. Chem. Soc., Perkin Trans. 1 2002, 428 -
12a
Abramovitch RA.Cue BW. J. Am. Chem. Soc. 1976, 98: 1478 -
12b
Marvell EN. Thermal Electrocyclic ReactionsWasserman HH. Academic Press; New York: 1980. p.250 -
12c
Combes RC. Nitro and Nitroso Compounds, In Comprehensive Organic Chemistry Vol. 2:Barton D. Pergamon Press; Oxford: 1979. p.344 -
12d
Wróbel Z.Mąkosza M. Tetrahedron 1993, 49: 5315 -
12e
Wróbel Z.Mąkosza M. Tetrahedron 1997, 53: 5501 -
13a
Attanasi OA.Ballini R.Liao Z.Santeusanio S.Serra-Zanetti F. Tetrahedron 1993, 49: 7027 -
13b
Attanasi OA.De Crescentini L.Filippone P.Gatti G.Mantellini F.Santeusanio S. Tetrahedron 1998, 54: 7581 -
13c
Attanasi OA.Ballini R.De Crescentini L.Filippone P.Mantellini F. J. Org. Chem. 1999, 64: 9653
References and Notes
Synthesis of β-Nitroidrazones 3a-n; General Procedure: Nitroalkane 2a-c (1 mL) and NaOMe (5.4 mg, 0.1 mmol) were stirred at r.t. for 15 min. Then 1,2-diaza-1,3-butadiene 1a-f (2 mmol), as mixture of E/Z isomers,5a,b was added and the reaction mixture was allowed to stand at r.t. with magnetic stirring until complete disappearance of 1a-f was observed (monitored by silica gel TLC, for time see Table [1] ). β-Nitrohydrazone 3a-n was obtained by direct crystallization from the reaction medium or by evaporation of 2a-c under reduced pressure and recrystallization of the residue from Et2O-light PE (40-60 °C).
8Data for tert -Butyl 2-{2-[(Dimethylamino)carbonyl]-1-methyl-3-nitropentylidene}-1-hydrazinecarboxylate (3d): white powder. IR (nujol): 3259, 1734, 1708, 1646, 1552, 1519 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ = 0.86 (t, J = 7.6 Hz, 3 H), 1.39, 1.44 (2 × s, 9 H), 1.57-1.70 (m, 1 H), 1.75, 1.78 (2 × s, 3 H), 1.78-1.87 (m, 1 H), 2.80, 2.85, 3.05, 3.08 (4 × s, 6 H), 4.11, 4.17 (2 × d, J = 10.8, 12.0 Hz, 1 H), 4.93-5.00, 5.03-5.13 (2 × m, 1 H), 9.69, 9.76 (2 × s, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 9.1 (q), 10.0 (q), 13.0 (q), 13.3 (q), 24.6 (t), 26.3 (t), 28.0(q), 35.4 (q), 36.6 (q), 34.9 (q), 53.4 (d), 53.8 (d), 79.3 (s), 79.4 (d), 86.9 (d), 89.4 (d), 146.2 (s), 152.8 (s), 166.3 (s), 167.3 (s). MS (EI): m/z (%) = 315 (1) [M+ - 15], 257 (12), 228 (6), 210 (4), 184 (14), 167 (6), 155 (7), 139 (59), 128 (100). Anal. Calcd for C14H26N4O5: C, 50.90; H, 7.93; N, 16.96. Found: C, 51.00; H, 7.91; N, 16.95.
9Synthesis of Pyrazole-1-oxides 4a-n; General Procedure: A solution of β-nitrohydrazone 3a-n (2 mmol) and NaOMe (108 mg, 2 mmol) in MeOH (20 mL) was refluxed until complete disappearance of 3a-n was observed (monitored by silica gel TLC, for time see Table [2] ). The solvent was removed under reduced pressure and the residue was purified by chromatography on silica gel (elution mixture: EtOAc-MeOH = 95:5). Finally, products 4a-n were crystallized from hot EtOAc-MeOH.
10Data for 2-[( tert -Butoxycarbonyl)amino]-4-[(dimethyl-amino)carbonyl]-5-ethyl-3-methylpyrazole-1-oxide (4d): colorless crystals; mp 167-168 °C with decomposition. IR (nujol): 3108, 1741, 1637, 1541 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.05 (t, J = 7.6 Hz, 3 H), 1.28, 1.45 (2 × s, 9 H), 2.03 (s, 3 H), 2.42-2.58 (m, 2 H), 2.94 (s, 6 H), 10.18, 10.54 (2 × s, 1 H). 13C NMR (100 MHz, DMSO-d 6): δ = 9.7 (q), 10.8 (q), 17.0 (t), 27.5 (q), 27.5 (q), 27.7 (q), 34.3 (q), 37.9 (q), 81.3 (s), 81.7 (s), 106.9 (s), 126.1 (s), 126.6 (s), 153.3 (s), 153.5 (s)163.1 (s). MS (EI): m/z (%) = 312 (36) [M+], 296 (2), 256 (100). Anal. Calcd for C14H24N4O4: C, 53.83; H, 7.74; N, 17.94. Found: C, 53.87; H, 7.76; N, 17.91.
11Data for 2-[( tert -Butoxycarbonyl)amino]-4-[(diethyl-amino)carbonyl]-5-ethyl-3-methylpyrazole-1-oxide (4j): colorless crystals; mp 145-148 °C with decomposition. IR (nujol): 3097, 1740, 1623, 1519, 1530 cm-1. 1H NMR (400 MHz, DMSO-d 6, 22 °C): δ = 0.98-1.10 (m, 9 H), 1.29, 1.45 (2 × s, 9 H), 2.01, 2.04 (2 × s, 3 H), 2.39-2.61 (m, 2 H), 3.14-3.52 (m, 4 H), 10.13, 10.51 (2 × br s, 1 H). 1H NMR (400 MHz, DMSO-d 6, 60 °C): δ = 1.07 (t, J = 7.4 Hz, 9 H), 1.43 (br s, 9 H), 2.02 (s, 3 H), 2.49 (q, J = 7.4 Hz, 3 H), 3.35 (q, J = 6.9 Hz, 6 H), 10.28 (br s, 1 H). 13C NMR (100 MHz, DMSO-d 6, 22 °C): δ = 9.5 (q), 10.7 (q), 13.9 (q), 14.0 (q), 17.0 (t), 27.4 (q), 27.7 (q), 42.5 (t), 42.6 (t), 81.3 (s), 81.7 (s), 107.4 (s), 125.6 (s), 125.7 (s), 153.5 (s), 162.5 (s). MS (EI): m/z (%) = 340 (50) [M+], 324 (1), 283 (100). Anal. Calcd for C16H28N4O4: C, 56.45; H, 8.29; N, 16.46. Found: C, 56.31; H, 8.31; N, 16.51.
14Crystallographic data (excluding structure factors) for compound 4d have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 621653 ([a] Polymorph 1) and CCDC 621654 ([b] Polymorph 2). Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44 (1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].