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

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

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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

1a Ali NA, Dar BA, Pradhan V, Farooqui M. Mini-Rev. Med. Chem. 2013; 13: 1792
1b Schmidt A, Beutler A, Snovydovych S. Eur. J. Org. Chem. 2008; 4073

2 Jiang R, Frackowiak B, Shin Y, Song X, Chen W, Lin L, Cameron MD, Duckett DR, Kamenecka TM. Bioorg. Med. Chem. Lett. 2013; 23: 2683
3 Corsi G, Palazzo G, Germani C, Barcellona PS, Silvestrini B. J. Med. Chem. 1976; 19: 778
4 Conway GA, Loeffler JL, Hall IH. J. Med. Chem. 1983; 26: 876
5 Lee F.-Y, Lien J.-C, Huang L.-J, Huang T.-M, Tsai S.-C, Teng C.-M, Wu C.-C, Cheng F.-C, Kuo S.-C. J. Med. Chem. 2001; 44: 3746
6 Li X, Chu S, Feher VA, Khalili M, Nie Z, Margosiak S, Nikulin V, Levin J, Sprankle KG, Tedder ME, Almassy R, Appelt K, Yager KM. J. Med. Chem. 2003; 46: 5663
7 Rooney L, Vidal A, D’Souza AM, Devereux N, Masick B, Boissel V, West R, Head V, Stringer R, Lao J, Petrus MJ, Patapoutian A, Nash M, Stoakley N, Panesar M, Verkuyl JM, Schumacher AM, Petrassi HM, Tully DC. J. Med. Chem. 2014; 57: 5129

8a Lebedev AY, Khartulyari AS, Voskoboynikov AZ. J. Org. Chem. 2005; 70: 596
8b Liu R, Zhu Y, Qin L, Ji S. Synth. Commun. 2008; 38: 249
8c Bae YK, Cho CS. Appl. Organomet. Chem. 2013; 27: 224
8d Gao M, Liu X, Wang X, Cai Q, Ding K. Chin. J. Chem. 2011; 29: 1199

9a Varughese DJ, Manhas MS, Bose AK. Tetrahedron Lett. 2006; 47: 6795
9b Creencia EC, Kosaka M, Muramatsu T, Kobayashi M, Iizuka T, Horaguchi T. J. Heterocycl. Chem. 2009; 46: 1309

10 Wray BC, Stambuli JP. Org. Lett. 2010; 12: 4576
11 Xiong X, Jiang Y, Ma D. Org. Lett. 2012; 14: 2552

12a Mahdavi M, Asadi M, Saeedi M, Rezaei Z, Moghbel H, Foroumadi A, Shafiee A. Synlett 2012; 23: 2521
12b Saeedi M, Mahdavi M, Foroumadi A, Shafiee A. Tetrahedron 2013; 69: 3506
12c Mahdavi M, Asadi M, Saeedi M, Ebrahimi M, Rasouli MA, Ranjbar PR, Foroumadi A, Shafiee A. Synthesis 2012; 44: 3649

13a Tamura R, Kamimura A, Ono N. Synthesis 1991; 423
13b Denney DB, Denney DZ, Perez AJ. Tetrahedron 1993; 49: 4463

14 Kislyi KA, Samet AV, Strelenko YA, Semenov VV. J. Org. Chem. 2008; 73: 2285
15 Filimonov SI, Chirkova ZV, Abramov IG, Firgang SI, Stashina GA, Strelenko YA, Khakimov DV, Pivina TS, Samet AV, Suponitsky KY. Tetrahedron 2012; 68: 5991
16 Farkas R, Törincsi M, Kolonits P, Fekete J, Alonso OJ, Novak L. Cent. Eur. J. Chem. 2010; 8: 300
17 Gorvin JH, Whalley DP. J. Chem. Soc., Perkin Trans. 1 1979; 1364
18 Pearson DE, Buehler CA. Chem. Rev. 1974; 74: 45
19 Yanagisawa S, Ueda K, Taniguchi T, Itami K. Org. Lett. 2008; 10: 4673
20 Roman DS, Takahashi Y, Charette AB. Org. Lett. 2011; 13: 3242

21a Trofimov BA, Schmidt EY, Zorina NV, Ivanova EV, Ushakov IA. J. Org. Chem. 2012; 77: 6880
21b Trofimov BA, Schmidt EYu, Ushakov IA, Zorina NV, Skital’tseva EV, Protsuk NI, Mikhaleva AI. Chem. Eur. J. 2010; 16: 8516

22 Mahdavi M, Foroughi N, Saeedi M, Karimi M, Alinezhad H, Foroumadi A, Shafiee A, Akbarzadeh T. Synlett 2014; 25: 385

23a Starosotnikov AM, Lobach AV, Kachala VV, Shevelev SA. Russ. Chem. Bull., Int. Ed. 2004; 53: 584
23b Starosotnikov AM, Kachala VV, Lobach AV, Vinogradov VM, Shevelev SA. Russ. Chem. Bull., Int. Ed. 2003; 52: 1782

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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