Potassium tert-Butoxide Promoted Intramolecular Amination of 1-Aryl-2-
(2-nitrobenzylidene)hydrazines: Efficient Synthesis of 1-Aryl-1H-indazoles

Fatemeh Esmaeili-Marandi; Mina Saeedi; Mohammad Mahdavi; Issa Yavari; Alireza Foroumadi; Abbas Shafiee

doi:10.1055/s-0034-1379084

Synlett, Inhaltsverzeichnis

Synlett 2014; 25(18): 2605-2608
DOI: 10.1055/s-0034-1379084

letter

Potassium tert-Butoxide Promoted Intramolecular Amination of 1-Aryl-2- (2-nitrobenzylidene)hydrazines: Efficient Synthesis of 1-Aryl-1H-indazoles

Authors

Fatemeh Esmaeili-Marandi

^aDepartment of Chemistry, College of Basic Sciences, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran
Mina Saeedi

^bDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Fax: +98(21)66461178 eMail: shafieea@tums.ac.ir
Mohammad Mahdavi

^bDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Fax: +98(21)66461178 eMail: shafieea@tums.ac.ir
Issa Yavari

^aDepartment of Chemistry, College of Basic Sciences, Tehran Science and Research Branch, Islamic Azad University, Tehran, Iran
Alireza Foroumadi

^bDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Fax: +98(21)66461178 eMail: shafieea@tums.ac.ir
Abbas Shafiee*

^bDepartment of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran Fax: +98(21)66461178 eMail: shafieea@tums.ac.ir

Abstract

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Abstract

1-Aryl-2-(2-nitrobenzylidene)hydrazines readily undergo intramolecular amination to afford 1-aryl-1H-indazole derivatives. The reaction was conducted in the presence of potassium tert-butoxide in N,N-dimethylformamide (DMF) at 100 °C and all products were obtained in good yields. Displacement of the nitro group was achieved in the absence of significant electron-withdrawing substituents such as nitro, cyanide, diazo, or carbonyl groups.

Key words

potassium tert-butoxide - indazoles - hydrazines - amination - nitro displacement

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Referenzen

References and Notes

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24 Synthesis of Indazole Derivatives 2; General Procedure: A mixture of 1-aryl-2-(2-nitrobenzylidene)hydrazine 1 (1 mmol) and t-BuOK (1 mmol) in DMF (5 mL) was stirred at 100 °C for 40–60 min. Upon completion (reaction monitored by TLC) the reaction mixture was poured into cold water and the precipitate was filtered off to obtain pure products 2 with no need for further purification. 1-Phenyl-1H-indazole (2a) Yield: 0.16 g (85%); off-white solid; mp 72–74 °C (Lit.^8a 76–78 °C). IR (KBr): 1598, 1504, 1465 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.26 (t, J = 8.0 Hz, 1 H, H-4′), 7.39 (t, J = 7.6 Hz, 1 H, H-6), 7.46 (t, J = 7.6 Hz, 1 H, H-5), 7.57 (t, J = 8.0 Hz, 2 H, H-3′, H-5′), 7.76–7.78 (m, 3 H, H-4, H-2′, H-6′), 7.84 (d, J = 7.6 Hz, 1 H, H-7), 8.24 (s, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 110.4, 121.3, 121.5, 122.8, 125.3, 126.6, 127.1, 129.5, 135.4, 138.8, 140.2. Anal. Calcd for C₁₃H₁₀N₂: C, 80.39; H, 5.19; N, 14.42. Found: C, 80.56; H, 5.33; N, 14.61. 1-(4-Fluorophenyl)-1H-indazole (2b) Yield: 0.18 g (85%); off-white solid; mp 84–86 °C (Lit.²⁵ 90 °C). IR (KBr): 1641, 1614, 1516 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.24–7.28 (m, 3 H, H-6, H-3′, H-5′), 7.46 (t, J = 8.0 Hz, 1 H, H-5), 7.69–73 (m, 3 H, H-4, H-2′, H-6′), 7.83 (d, J = 8.0 Hz, 1 H, H-7), 8.22 (s, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 110.1, 116.3 (d, J _C–F = 22.8 Hz), 121.4, 121.6, 124.6 (d, J _C–F = 19.1 Hz), 125.2, 127.3, 135.4, 136.3, 138.9, 161.1 (d, J _C–F= 245 Hz). Anal. Calcd for C₁₃H₉FN₂: C, 73.57; H, 4.27; N, 13.20. Found: C, 73.69; H, 4.41; N, 13.38. 1-(4-Bromophenyl)-1H-indazole (2c) Yield: 0.24 g (90%); off-white solid; mp 85–87 °C (Lit.^8a 81–83 °C). IR (KBr): 1644, 1617, 1492 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.27 (t, J = 8.0 Hz, 1 H, H-6), 7.47 (t, J = 8.0 Hz, 1 H, H-5), 7.64–7.69 (m 4 H, H-2′, H-3′, H-5′, H-6′), 7.74 (d, J = 8.0 Hz, 1 H, H-4), 7.83 (d, J = 8.0 Hz, 1 H, H-7), 8.23 (s, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 110.2, 119.8, 121.5, 121.8, 124.0, 125.5, 127.5, 132.5, 135.9, 138.6, 139.3. Anal. Calcd for C₁₃H₉BrN₂: C, 57.17; H, 3.32; N, 10.26. Found: C, 57.34; H, 3.18; N, 10.05. 5-Chloro-1-phenyl-1H-indazole (2d) Yield: 0.19 g (85%); off-white solid; mp 114–116 °C (Lit.^8d 116–117 °C). IR (KBr): 1620, 1507, 1459 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.40–7.43 (m, 2 H, H-6, H-4′), 7.57 (t, J = 8.0 Hz, 2 H, H-3′, H-5′), 7.67–7.72 (m, 3 H, H-7, H-2′, H-6′), 7.84 (d, J = 1.6 Hz, 1 H, H-4), 8.16 (s, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 111.5, 120.5, 122.8, 126.1, 127.0, 127.1, 127.8, 129.6, 134.6, 137.3, 139.8. Anal. Calcd for C₁₃H₉ClN₂: C, 68.28; H, 3.97; N, 12.25. Found: C, 68.11; H, 4.15; N, 12.38. 5-Chloro-1-(4-fluorophenyl)-1H-indazole (2e) Yield: 0.20 g (83%); off-white solid; mp 84–86 °C. IR (KBr): 1638, 1522, 1410 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.23–7.28 (m, 2 H, H-2′, H-6′), 7.39 (dd, J = 8.8, 2.0 Hz, 1 H, H-6), 7.59 (d, J = 8.8 Hz, 1 H, H-7), 7.66 (dd, J = 8.8, 4.8 Hz, 2 H, H-3′, H-5′), 7.84 (d, J = 2.0 Hz, 1 H, H-4), 8.14 (s, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 111.2, 116.4 (d, J _C–F= 22.9 Hz), 120.5, 124.6 (d, J _C–F= 8.3 Hz), 126.0, 127.2, 135.4, 134.6, 135.9 (d, J _C–F= 2.9 Hz), 137.4, 161.4 (d, J _C–F= 245 Hz). Anal. Calcd for C₁₃H₈ClFN₂: C, 63.30; H, 3.27; N, 11.36. Found: C, 63.12; H, 3.42; N, 11.51. 1-(4-Bromophenyl)-5-chloro-1H-indazole (2f) Yield: 0.26 g (85%); off-white solid; mp 115–116 °C. IR (KBr): 1638, 1589, 1504 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.40 (dd, J = 8.8 Hz, 1 H, H-6), 7.60 (d, J = 9.0 Hz, 2 H, H-3′, H-5′), 7.64 (d, J = 8.8 Hz, 1 H, H-7), 7.67 (d, J = 9.0 Hz, 2 H, H-2′, H-6′), 7.85 (d, J = 1.2 Hz, 1 H, H-4), 8.16 (s, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 111.3, 120.3, 120.6, 124.0, 126.3, 127.4, 128.0, 132.7, 135.1, 137.1, 138.8. Anal. Calcd for C₁₃H₈BrClN₂: C, 50.77; H, 2.62; N, 9.11. Found: C, 50.59; H, 2.81; N, 8.91. 5-Chloro-1-(4-methoxyphenyl)-1H-indazole (2g) Yield: 0.22 g (85%); off-white solid; mp 96–98 °C. IR (KBr): 1638, 1617, 1522 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.91 (s, 3 H, OMe), 7.08 (d, J = 8.8 Hz, 2 H, H-3′, H-5′), 7.37 (dd, J = 9.0, 2.0 Hz, 1 H, H-6), 7.57 (d, J = 9.0 Hz, 1 H, H-7), 7.59 (d, J = 8.8 Hz, 2 H, H-2′, H-6′), 7.78 (dd, J = 2.0, 0.8 Hz, 1 H, H-4), 8.16 (d, J = 0.8 Hz, 1 H, H-3). ¹³C NMR (100 MHz, CDCl₃): δ = 55.6, 111.3, 114.7, 120.3, 124.6, 125.7, 126.9, 127.5, 132.9, 134.0, 137.5, 158.7. Anal. Calcd for C₁₄H₁₁ClN₂O: C, 65.00; H, 4.29; N, 10.83. Found: C, 65.23; H, 4.51; N, 10.67. 5-Chloro-1-(4-nitrophenyl)-1H-indazole (2h) Yield: 0.24 g (88%); off-white solid; mp 229–231 °C. IR (KBr): 1641, 1623, 1592, 1504, 1334 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 7.50 (dd, J = 8.8, 2.0 Hz, 1 H, H-6), 7.80 (d, J = 8.8 Hz, 1 H, H-7), 7.84 (dd, J = 2.0, 0.4 Hz, 1 H, H-4),7.97 (d, J = 9.2 Hz, 2 H, H-2′, H-6′), 8.25 (d, J = 0.4 Hz, 1 H, H-3), 8.45 (d, J = 9.2 Hz, 2 H, H-3′, H-5′). ¹³C NMR (100 MHz, CDCl₃): δ = 111.6, 121.1, 121.6, 125.4, 127.2, 128.3, 128.8, 136.8, 137.1, 144.9, 145.4. Anal. Calcd for C₁₃H₈ClN₃O₂: C, 57.05; H, 2.95; N, 15.35. Found: C, 56.88; H, 3.20; N, 15.57.
25 Elguero J, Estopa C, Ilavsky D. J. Chem. Res. 1981; 4237

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