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Synlett 2014; 25(6): 889-893
DOI: 10.1055/s-0033-1340737
DOI: 10.1055/s-0033-1340737
letter
A New Versatile Route to the Synthesis of a Novel Series of Highly Substituted 1,1′-Carbonylbispyrazole Derivatives
Further Information
Publication History
Received: 05 December 2013
Accepted after revision: 15 January 2014
Publication Date:
14 February 2014 (online)
Abstract
The reaction of 1H-pyrazole-1-carbohydrazide with various α,β-unsaturated nitriles under suitable conditions leads to a cyclocondensation reaction, thereby providing a novel route for the synthesis of a series of highly substituted 1,1′-carbonylbispyrazole derivatives.
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References and Notes
- 1 Vujasinovic I, Paravic A, Mlinaric MK, Brajsa K, Bertosa B. Bioorg. Med. Chem. 2012; 20: 2101
- 2 Zhang CY, Liu XH, Wang BL, Wang SH, Li ZM. Chem. Biol. Drug Des. 2010; 75: 489
- 3 Gadakh AV, Pandit C, Rindhe SS, Karale BK. Bioorg. Med. Chem. Lett. 2010; 20: 5572
- 4 Lv HS, Han QQ, Ding XL, Zhou JL, Yang PS, Miao JY, Zhao BX. Arch. Pharm. 2012; 345: 870
- 5 Bing RJ, Lomnicka M. J. Am. Coll. Cardiol. 2002; 39: 521
- 6 Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro J, Penning TD, Seibert K, Isakson PC, Stallings WC. Nature (London) 1996; 384: 644
- 7a Seo HJ, Kim MJ, Lee SH, Lee SH, Kim ME, Kim J, Lee J. Bioorg. Med. Chem. 2010; 18: 1149
- 7b Yan L, Huo P, Debenham JS, Madsen-Duggan CB, Lao J, Chen RZ, Xiao JC, Shen CP, Stribling DS, Shearman LP, Strack AM, Tsou N, Ball RG, Wang JX, Tong T, Bateman TJ, Reddy VB. G, Fong TM, Hale JJ. J. Med. Chem. 2010; 53: 4028
- 8a Cho YS, Borland M, Brain C, Chen CH.-T, Cheng H, Chopra R, Chung K, Groarke J, He G, Hou Y, Kim S, Kovats S, Lu Y, O’Reilly M, Shen J, Smith T, Trakshel G, Vögtle M, Xu M, Sung MJ. J. Med. Chem. 2010; 53: 7938
- 8b Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL, Heathcote M, Maman S, Matthews JE, McMenamin RL, Navarro EF, O’Brien MA, O’Reilly M, Rees DC, Reule M, Tisi D, Williams G, Vinkovic M, Wyatt PG. J. Med. Chem. 2009; 52: 379
- 8c Diaz JL, Cuberes R, Berrocal J, Contijoch M, Christmann U, Fernández A, Port A, Holenz J, Buschmann H, Laggner C, Serafini MT, Burgueno J, Zamanillo D, Merlos M, Vela JM, Almansa C. J. Med. Chem. 2012; 55: 8211
- 9a Jones Raymond CF, Seager Laura E, Elsegood Mark RJ. Synlett 2011; 211
- 9b Vijesh AM, Isloor AM, Shetty P, Sundershan S, Fun HK. Eur. J. Med. Chem. 2013; 62: 410
- 9c Jiang J, Du C, Gu C, Ji Y. Synlett 2012; 23: 2965
- 9d Aly HM, El-Gazzar MG. Arzneim. Forsch. 2012; 62: 105
- 9e Adib M, Mohammadi B, Bijanzadeh H. Synlett 2008; 3180
- 9f Morrill C, Babu S, Almstead NG, Moon Y. Synthesis 2013; 45: 1791
- 9g Reddy HR, Vijaykumar J, Gree R. Synthesis 2013; 45: 830
- 9h Janin YL. Org. Chem. 2010; 7: 314
- 9i Siegmund A, Retz D, Xi N, Dominguez C, Burli R, Liu L. Synlett 2008; 1005
- 9j Willy B, Mouller TJ. J. Org. Lett. 2011; 13: 2082
- 9k Rosa A, Machado P, Vargas S, Bonacorso HG, Zanatta N, Martins MA. P. Synlett 2008; 1673
- 10a Denisova AB, Sosnovskikh VY, Dehaen W, Toppet S, Meervelt LV, Bakulev VA. J. Fluorine Chem. 2002; 115: 183
- 10b Shawali AS, Sherif SM, El-Merzabani MM, Darwish MA. A. J. Heterocycl. Chem. 2009; 46: 548
- 11 Hanamoto T, Hakoshima Y, Egashira M. Tetrahedron Lett. 2004; 45: 7573
- 12 Angerman A, Franke H, Geisler J, Johann G, Rees R. US 4008200, 1991
- 13 Hoffmann A, Flörke U, Schürmann M, Herres-Pawlis S. Eur. J. Org. Chem. 2010; 4136
- 14 Otero A, Fernandez-Baeza J, Lara-Sanchez A, Tejeda J, Sanchez-Barba LF. Eur. J. Inorg. Chem. 2008; 5309
- 15 Heitaro O, Takashi I, Kazuhisa S, Tetsuo O. US 612130519, 2000
- 16a Rostom SA. F. Bioorg. Med. Chem. 2010; 18: 2767
- 16b Francisco ME. Y, Seltzman HH, Gilliam AF, Mitchell RA, Rider SL, Pertwee RG, Stevenson LA, Thomas BF. J. Med. Chem. 2002; 45: 2708
- 17 Soliman R, Darwish SA. S. J. Med. Chem. 1983; 11: 1959
- 18 Sheludyakov VD, Shedulyakova SV, Kuznetsova MG, Silkina NN, Mironov VF. Zh. Obshch. Khim. 1980; 4: 875
- 19 Scherer J, Klausener A, Soellner R. DE 10035011, 2002
- 20 Esteves-Souza A, Echevarrıa A, Vencato I, Jimeno ML, Elguero J. Tetrahedron 2001; 57: 6147
- 21 Byers PK, Canty AJ, Honeyman RT, Gardinier JR, Reger DL. Inorg Synth. 2004; 34: 30
- 22 Tang L, Jia W, Wang Z, Wang H. J. Organomet. Chem. 2002; 649: 152
- 23 Katritsky AR, Rees CW, Scriven EF. V. Comprehensive Heterocyclic Chemistry II . Vol. 3. Elsevier Science; New York: 1996
- 24 Safaei S, Mohammadpoor-Baltork I, Khosropour AR, Moghadam M, Tangestaninejad S, Mirkhani V, Khavasi HR. Synlett 2013; 24: 1086
- 25 Bonacorso HG, Cechinel CA, Porte LM. F, Navarini J, Cavinatto SR, Sehnem C, Martins DB, Zanatta N, Martins MA. P. J. Heterocycl. Chem. 2010; 47: 1073
- 26 General Procedure for the Synthesis of Pyrazoles 2 A mixture of 4 (82 mmol) and hydrazinecarboxylic acid ethyl ester (1, 8.52 g, 81 mmol) was stirred under reflux in abs. EtOH (120 mL) for 4 h. After cooling in the refrigerator overnight, the precipitate was filtered and washed with cold Et2O to afford 2 as colorless needles. Ethyl 5-Amino-4-cyano-1H-pyrazole-1-carboxylate (2a) Yield 12.4 g (84%); mp 165–167 °C. IR: νmax = 3493, 3280, 3214, 3128–3156, 2219, 1771, 1628 cm–1. 1H NMR (100 MHz, CDCl3): δ = 1.48 (t, 3 H, CH3), 4.54 (q, 2 H, CH2), 6.32 (s, 2 H, NH2), 7.57 (s, 1 H, CH). Ethyl 5-Amino-4-cyano-3-methyl-1H-pyrazole-1-carboxylate (2b) Yield 12.7 g (81%); mp 180–181 °C. IR: νmax = 3406, 3320, 3247, 2990, 2213, 1736, 1646, 1563, 1471, 1332, 1256, 1021 cm–1. 1H NMR (100 MHz, CDCl3): δ = 1.43 (t, 3 H, CH3), 2.25 (s, 3 H, CH3), 4.48 (q, 2 H, CH2), 6.48 (s, 2 H, NH2). Anal. Calcd for C8H10N4O2: C, 49.48; H, 5.19; N, 28.85. Found: C, 49.38; H, 5.11; N, 28.78.
- 27 General Procedure for the Synthesis of 1H-Pyrazole-1-carbohydrazides 3 Hydrazine monohydrate (10 mL, 206 mmol) was added to a solution of 2 (55 mmol) in abs. EtOH (60 mL), and the mixture was refluxed for 3 h. The excess of solvent was distilled off, and the crude product obtained was poured into ice water. After cooling in the refrigerator overnight, the solid residue was filtered and washed with cold water and dried to give 3 as a white solid. 5-Amino-4-cyano-1H-pyrazole-1-carbohydrazide (3a) Yield 8.2 g (90%); mp 175 °C. IR: νmax = 3416, 3341, 3284, 3240, 3178, 2956, 2238, 1646, 1570, 1034 cm–1. 1H NMR (100 MHz, DMSO-d 6): δ = 6.82 (s, 4 H, 2 NH2), 7.72 (s, 1 H, CH), 12.09 (s, 1 H, NH). Anal. Calcd for C5H6N6O: C, 36.15; H, 3.64; N, 50.58. Found: C, 36.08; H, 3.58; N, 50.49. 5-Amino-4-cyano-3-methyl-1H-pyrazole-1-carbohydrazide (3b) Yield 7.9g (80%); mp 125–127 °C. IR: νmax = 3403, 3341, 3284, 3242, 2994, 2217, 1660, 1298 cm–1. 1H NMR (100 MHz, CD3COCD3): δ = 2.20 (s, 3 H, CH3), 5.35 (s, 4 H, 2 NH2), 11.19 (s, 1 H, NH). Anal. Calcd for C6H8N6O: C, 40.00; H, 4.48; N, 46.65. Found: C, 39.01; H, 4.41; N, 46.60.
- 28 Dooley MJ, Quinn RJ, Scammells PJ. Aust. J. Chem. 1989; 42: 747
- 29 Ferlin M, Grazia MB, Valerio DA. Tetrahedron 2006; 62: 6222
- 30 Thomae D, Perspicace E, Henryon D, Xu Z, Hesse S, Kirsch G, Schneider S, Seck P. Tetrahedron 2009; 65: 10453
- 31 Amico JJ, Ruminski PG, Suba LA, Freeman JJ, Dahl WE. Phosphorus Sulfur Relat. Elem. 1985; 21: 307
- 32 Wu Y, Li H, Yang H. Org. Biomol. Chem. 2010; 8: 3394
- 33 Liang D, Wang M, Bekturhun B, Xiong B, Liu Q. Adv. Synth. Catal. 2010; 352: 1593
- 34 Synthesis of 1,1′-Carbonylbis(5-amino-1H-pyrazole-4-carbonitrile) (5a) Compound 4a (0.62 g, 5 mmol) was added to a stirring solution of 3a (0.82 g, 5 mmol) in EtOH (10 mL). The contents were stirred at r.t. for a further 30 min and then refluxed for 3 h. After the completion of the reaction [monitoring by TLC using CHCl3–MeOH (4:1, v:v) as eluent], the white solid was filtered under suction and washed with cold EtOH (1.1g, 93%); mp >300 °C (dec.). IR: νmax = 3321, 3277, 3126, 2235, 1688, 1610, 1570, 1487, 1338, 1329, 1262 cm–1. 1H NMR (100 MHz, DMSO-d 6): δ = 8.54 (s, 1 H, arom.), 8.72 (s, 1 H, arom.), 9.37 (br, 4 H, NH2, D2O exchangeable). Anal. Calcd for C9H6N8O: C, 44.63; H, 2.50; N, 46.27. Found: C, 44.54; H, 2.55; N, 46.12. Synthesis of 5-Amino-1-(5-amino-4-cyano-1H-pyrazole-1-carbonyl)-3-methyl-1H-pyrazole-4-carbonitrile (5b) Compounds 4b (0.54 g, 4 mmol) and 3a (0.66 g, 4 mmol) were added to a solution of Na of NaOEt prepared by adding (0.21 g, 9 mmol) to abs. EtOH (10 mL). The mixture was stirred at r.t. for 30 min and then heated to reflux for 3 h. After the completion of the reaction [monitoring by TLC using CHCl3–MeOH (3:1, v/v) as eluent], the mixture was cooled to r.t. H2O (5 mL) was added, and the mixture was neutralized by HCl. The collected solid was recrystallized from MeOH (0.81 g, 81%); mp >300 °C (dec.). IR: νmax = 3340, 3310, 3248, 3180, 3116, 2232, 2221, 1650, 1594 cm–1. 1H NMR (100 MHz, DMSO-d 6): δ = 2.52 (s, 3 H, CH3), 8.67 (s, 1 H, arom.), 9.25 (br, 4 H, NH2, D2O exchangeable). 13C NMR (100 MHz, DMSO-d 6): δ = 24.3, 77.4, 81.1, 113.9, 115.5, 147.9,150.6, 150.9, 164.6. Anal. Calcd for C10H8N8O: C, 46.88; H, 3.15; N, 43.73. Found: C, 46.78; H, 3.04; N, 43.60.
- 35 General Procedure for the Synthesis of 1,1′-Carbonylbispyrazole Derivatives 5c–f A mixture of of 4c–e (4 mmol) and 3 (4 mmol) in pyridin (5 mL) was heated to reflux for 4 h, then poured onto ice water and the mixture neutralized with concd HCl. The precipitated solid was filtered, washed with H2O, and crystallized from an appropriate solvent. 5-Amino-1-(5-amino-4-cyano-1H-pyrazole-1-carbonyl)-3-(methylthio)-1H-pyrazole-4-carbonitrile (5c) Yield 0.89 g (78%, DMF); mp >300 °C. IR: νmax = 3353, 3304, 3027, 3186, 2240, 2218, 1659, 1607, 1567, 1384, 1342, 1291 cm–1. 1H NMR (100 MHz, DMSO-d 6): δ = 2.64 (s, 3 H, SCH3), 8.37 (s, 1 H, arom.), 9.03 (br, 4 H, NH2, D2O exchangeable). 13C NMR (100 MHz, DMSO-d 6): δ = 13.2, 74.6, 80.9, 113.9, 114.3, 147.7, 150.1, 150.4, 166.5. Anal. Calcd for C10H8N8OS: C, 41.66; H, 2.80; N, 38.87; S, 11.12. Found: C, 41.56; H, 2.46; N, 38.57; S, 11.04. 5-Amino-1-[4-amino-5-cyano-3-(ethylthio)-1H-pyrazole-1-carbonyl]-1H-pyrazole-4-carbonitrile (5d) Yield 1.05g (87%, EtOH); mp >300 °C (dec.). IR: νmax = 3350, 3320, 3252, 3187, 3101, 2994, 2941, 2217, 1657, 1597, 1563, 1534, 1465, 1380, 1339, 1286, 1248 cm–1. 1H NMR (100 MHz, DMSO-d 6): δ = 1.26–1.41 (t, 3 H, SCH2CH3), 3.11–3.30 (q, 2 H, SCH2CH3), 8.62 (s, 1 H, arom.), 9.19 (br, 4 H, NH2, D2O exchangeable). 13C NMR (100 MHz, DMSO-d 6): δ = 15.7, 25.8, 75.8, 81.9, 115.3, 148.8, 151.4, 151.6, 167.2. Anal. Calcd for C11H10N8OS: C, 43.70; H, 3.33; N, 37.07; S, 10.61. Found: C, 51.64; H, 3.29; N, 37.42; S, 10.55. Ethyl 1-(5-Amino-4-cyano-1H-pyrazole-1-carbonyl)-5-methyl-3-(methylthio)-1H-pyrazole-4-carboxylate (5e) Yield 1.09g (82%, n-hexane); mp 128–129 °C. IR: νmax = 3351, 3313, 3250, 3219, 3184, 2239, 2217, 1658, 1607, 1566, 1534, 1462, 1384, 1342, 1278 cm–1. 1H NMR (100 MHz, CDCl3): δ = 1.38–1.52 (t, 3 H, OCH2CH3), 2.65 (s, 3 H, CH3), 2.88 (s, 3 H, SCH3), 4.33–4.56 (q, 2 H, OCH2CH3), 8.29 (s, 1 H, arom.). 13C NMR (100 MHz, DMSO-d 6): δ = 14.1, 14.2, 15.3, 62.8, 81.9, 112.9, 115.4, 146.6, 147.4, 149.0, 164.1, 164.6. Anal. Calcd for C13H14N6O3S: C, 46.70; H, 4.22; N, 25.14; S, 9.59. Found: C, 46.62; H, 4.15; N, 25.09; S, 9.59. 5-Amino-1-(4-amino-5-cyano-3-methyl-1H-pyrazole-1-carbonyl)-1H-pyrazole-4-carbonitrile (5f) Yield 0.87g (81%, MeOH). IR: νmax = 3327, 3277, 3120, 2234, 1680, 1609, 1565, 1485, 1335 cm–1. 1H NMR (100 MHz, DMSO-d 6): δ = 2.47 (s, 3 H, CH3), 2.52 (s, 3 H, CH3), 9.13 (br, 4 H, 2 NH2, D2O exchangeable). 1H NMR (100 MHz, CD3COCD3): δ = 2.49 (s, 3 H, CH3), 2.59 (s, 3 H, CH3), 8.40 (br, 4 H, 2 NH2, D2O exchangeable). Anal. Calcd for C11H10N8O: C, 48.89; H, 3.73; N, 41.46. Found: C, 48.81; H, 3.69; N, 41.40.
For recent pyrazole syntheses, see for example: