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Synlett 2013; 24(1): 41-44
DOI: 10.1055/s-0032-1317712
DOI: 10.1055/s-0032-1317712
letter
Consecutive Tandem Cycloaddition between Nitriles and Azides; Synthesis of 5-Amino-1H-[1,2,3]-triazoles
Further Information
Publication History
Received: 19 September 2012
Accepted after revision: 08 November 2012
Publication Date:
06 December 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201301/lookinside/thumbnails/10.1055-s-0032-1317712-1.jpg)
Abstract
Novel 5-amino-1H-1,2,3-triazoles were synthesized by a new synthetic route that involves consecutive tandem cycloaddition between nitriles and azides.
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References and Notes
- 1 Melo JO. F, Donnici CL, Augusti R, Ferreira VF, Souza MC. B. V, Ferreira ML. G, Cunha AC. Quim. Nova 2006; 29: 569
- 2 Sharma P, Kumar A, Upadhyay S, Singh J, Sahu V. Med. Chem. Res. 2010; 19: 589
- 3 Boechat N, Ferreira VF, Ferreira SB, Ferreira ML. G, da Silva FC, Bastos MM, Costa MS, Lourenço MC. S, Pinto AC, Krettli AU, Aguiar AC, Teixeira BM, da Silva NV, Martins PR. C, Bezerra FA. F. M, Camilo AL. S, da Silva GP, Costa CC. P. J. Med. Chem. 2011; 54: 5988
- 4 Cunha AC, Figueiredo JM, Tributino JL. M, Miranda AL. P, Castro HC, Zingali RB, Fraga CA. M, de Souza MC. B. V, Ferreira VF, Barreiro EJ. Bioorg. Med. Chem. 2003; 11: 2051
- 5 Ferreira SB, Sodero AC. R, Cardoso MF. C, Lima ES, Kaiser CR, Silva FP. Jr, Ferreira VF. J. Med. Chem. 2010; 53: 2364
- 6 da Silva FC, de Souza MC. B. V, Frugulhetti IC. P. P, Castro HC, Souza SL. O, Souza TM. L, Rodrigues DQ, de Souza AM. T, Abreu PA, Passamani F, Rodrigues CR, Ferreira VF. Eur. J. Med. Chem. 2009; 44: 373
- 7a da Settimo A, Livi O, Ferrarini PL, Biagi G. Farmaco, Ed. Sci. 1980; 35: 308
- 7b da Settimo A, Livi O, Ferrarini PL, Primofiore G. Farmaco, Ed. Sci. 1980; 35: 298
- 8 Zhang ZY, Liu Y, Zheng GY, Chen MQ, Yang SY. Acta Pharm. Sin. 1991; 26: 809
- 9 Biagi G, Calderone V, Giorgi I, Livi O, Scartoni V, Baragatti B, Martinotti E. Eur. J. Med. Chem. 2000; 35: 715
- 10 Baraldi PG, Cacciari B, Spalluto G, De Las Infants MJ. P, Zocchi C, Ferrara S, Dionisotti S. Farmaco, Ed. Sci. 1996; 51: 29
- 11 Freitas LB. O, Ruela FA, Pereira GR, Alves RB, Freitas RP, Santos LJ. Quim. Nova 2011; 34: 1791
- 12 Huisgen R. Angew. Chem., Int. Ed. Engl. 1963; 2: 565
- 13 Huisgen R, Szeimies G, Moebius L. Chem. Ber. 1967; 100: 2494
- 14 Tornøe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
-
15 Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
- 16 Biagi G, Giorgi I, Livi O, Lucacchini A, Martini C, Scartoni V. J. Pharm. Sci. 1993; 82: 893
- 17 Palacios F, Ochoa de Retana AM, Pagalday J. Heterocycles 1994; 38: 95
- 18 Boyer JH, Mack CH, Goebel N, Morgan LR. Jr. J. Org. Chem. 1958; 23: 1051
- 19 Tanaka Y, Miller SI. J. Org. Chem. 1973; 38: 2708
- 20a Smith CJ, Nikbin N, Ley SV, Lange H, Baxendale IR. Org. Biomol. Chem. 2011; 9: 1938
- 20b Rozhkov VY, Batog LV, Shevtsova EK, Struchkova MI. Mendeleev Commun. 2004; 14: 76
- 21a Lieber E, Chao TS, Rao CN. R. Org. Synth. 1957; 37: 26
- 21b Smith PA. S, Friar JJ, Resemann W, Watson AC. J. Org. Chem. 1990; 55: 3351
- 21c L’Abbe G, Hassner A. J. Heterocycl. Chem. 1970; 7: 361
- 22 L’Abbe G, Beenaerts L. Tetrahedron 1989; 45: 749
- 23 Jordão AK, Ferreira VF, Souza TM. L, Faria GG. S, Machado V, Abrantes JL, da Souza MC. B. V, Cunha AC. Bioorg. Med. Chem. 2011; 19: 1860
- 24 Campos VR, Abreu PA, Castro HC, Rodrigues CR, Jordão AK, Ferreira VF, de Souza MC. B. V, Santos FC, Moura LA, Domingos TS, Carvalho C, Sanchez EF, Fuly AL, Cunha AC. Bioorg. Med. Chem. 2009; 17: 7429
- 25 Dabak K, Sezer Z, Akar A, Anac O. Eur. J. Med. Chem. 2003; 38: 215
- 26 Costa MS, Boechat N, Rangel EA, da Silva FC, de Souza AM. T, Rodrihuez CR, Castro HC, Junior IN, Lourenço MC. S, Wardell SM. S. V, Ferreira VF. Bioorg. Med. Chem. 2006; 14: 8644
- 27 Ghoslan SA. S, Abdelhamid IA. A, Ibrahin HM, Elnagdi MH. ARKIVOC 2006; (xv): 53
- 28 Kamijo S, Jin T, Huo Z, Yamamoto Y. Tetrahedron Lett. 2002; 43: 9707
- 29 Ueda S, Su M, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 8944
- 30 Liu H, He X, Choi HS, Yang K, Woodmansee D, Wang Z, Ellis DA, Wu B, He Y. PCT Int. Appl.. WO 2006047516–A2, 2006: 259 .
- 31 Preparation of Compounds 7a–h; General Procedure: To a solution of BuLi (2 mmol) in anhydrous THF (1.5 mL), was added a solution of the nitrile (acetonitrile or propionitrile; 2 mmol) in anhydrous THF (2 mL) at 0 °C and under an argon atmosphere. After 5 min, a solution of azide derivative 5 (2 mmol) in anhydrous THF (2 mL) was added. The reaction was allowed to warm to r.t. and monitored by TLC. Distilled H2O (10 mL) was then added and the mixture was extracted with EtOAc. The organic layer was dried with sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with increasing polarity gradient mixture of hexane and EtOAc.
- 32 1-Phenyl-1H-1,2,3-triazole-5-amine (7a): Yield: 84%; white solid; mp 107.4–108.2 °C. IR (KBr): 3446 (N-H) cm–1; 1H NMR (CDCl3–MeOD, 300 MHz): δ = 5.64 (br s, 2 H, NH2), 6.75 (s, 1 H, H-4), 6.78–6.93 (m, 1 H, H-4′), 7.07–7.11 (m, 2 H, H-3′ and H-5′), 7.24–7.30 (m, 2 H, H2′–H-6′); 13C NMR (CDCl3–MeOD, 75 MHz): δ = 128.8 (C-Ph), 120.0 (C-2′ and C-6′), 125.8 (C-4′), 130.1 (C-3′ and C-5), 134.60, 135.5; HRMS (ESI): m/z [M + H]+ calcd for C8H9N4: 161.1833; found: 161.0924.4-Methyl-1-phenyl-1H-1,2,3-triazole-5-amine (7b): Yield: 61%; white solid; mp 127.5–128.9 °C. IR (KBr): 3381 (N-H) cm–1; 1H NMR (CDCl3–MeOD, 300 MHz): δ = δ 2.23 (s, 3 H, CH3), 3.82 (br s, 2 H, NH2), 7.41–7.58 (m, 5 H, H-Ph); 13C NMR (CDCl3–MeOD, 75 MHz): δ = 9.5 (CH3), 123.8 (C-Ph), 126.0, 128.8 (C-Ph), 129.6 (C-Ph), 135.60, 137.5; HRMS (ESI): m/z [M + H]+ calcd for C9H11N4: 175.2099; found: 175.0977.1-(4-Chlorophenyl)-1H-1,2,3-triazole-5-amine (7c): Yield: 82%; brown solid; mp 118.6–119.7 °C. IR (KBr): 3297 (N-H), 831 (C-Cl) cm–1; 1H NMR (DMSO-d 6, 500 MHz): δ = 5.78 (br s, 2 H, NH2), 7.06 (s, 1 H, H-4), 7.75 (s, 4 H, H-2′, H-3′, H-5′ and H-6′); 13C NMR (CDCl3, 125 MHz): δ = 116.97 (C-5), 125.31 (C-Ph), 128.55 (C-1′), 129.43 (C-Ph), 132.70 (C-6′), 134.58 (C-4′); HRMS (ESI): m/z [M + H]+ calcd for C8H8ClN4: 195.6284; found: 195.0431.1-(4-Chlorophenyl)-4-methyl-1H-1,2,3-triazole-5-amine (7d): Yield: 76%; yellow solid; mp 139.6–140.3 °C; IR (KBr): 3340 (N-H), 834 (C-Cl) cm–1; 1H NMR (CDCl3–MeOD, 300 MHz): δ = 2.25 (s, 3 H, CH3), 7.51 (s, 2 H, H-3′ and H-5′), 7.52 (s, 2 H, H-2′ and H-6′); 13C NMR (CDCl3–MeOD, 75 MHz): δ = 9.4 (CH3), 124.9 (C-3′ and C-5′), 126.4 (C-5), 129.7 (C-2′ and C-6′), 134.0 (C-4), 134.6 (C-1′), 137.4 (C-4′); HRMS (ESI): m/z [M + H]+ calcd for C9H10ClN4: 209.6550; found: 209.0586.1-(1,2:3,4-Di-O-isopropylideno-α-d-galactopyranosyl)-1H-1,2,3-triazole-5-amine (7g): Yield: 82%; yellow solid; mp 179.0–181.4 °C; IR (KBr): 3410 (N-H), 2922 (C-C sugar unit), 2853 (C-C sugar unit), 1002–1212 (C-O-C sugar unit) cm–1; 1H NMR (CDCl3–MeOD, 500 MHz): δ = 1.28 (s, 3 H, CH3), 1.36 (s, 3 H, CH3), 1.38 (s, 3 H, CH3), 1.51 (s, 3 H, CH3), 4.14–4.25 (m, 2 H, H-5′ and H-6′), 4.26–4.40 (m, 2 H, H-4′ and H-6′), 4.49 (dd, J = 2.5, 4.0 Hz, 1 H, H-2′), 4.64 (dd, J = 7.8, 2.5 Hz, 1 H, H-3′), 5.50 (d, J = 4.0 Hz, 1 H, H-1′), 7.04 (s, 1 H, H-4); 13C NMR (CDCl3–MeOD, 125 MHz): δ = 24.4 (CH3), 24.8 (CH3), 25.9 (CH3), 26.0 (CH3), 49.6 (C-6′), 68.6 (C-5′), 70.4 (C-2′), 70.6 (C-3′), 71.1 (C-4′), 96.1 (C-1′), 109.3, 109.8; HRMS (ESI): m/z [M + H]+ calcd for C14H23N4O5: 327.3557; found: 327.1659.1-(1,2:3,4-Di-O-isopropylideno-α-d-galactopyranosyl)-4-methyl-1H-1,2,3-triazole-5-amine (7h): Yield: 54%; white solid; mp 204.2–205.6 °C; IR (KBr): 3450 (N-H), 2987 (C-C sugar unit), 2851 (C-C sugar unit), 1070–1237 (C-O-C sugar unit) cm–1; 1H NMR (CDCl3–MeOD, 300 MHz): δ 1H NMR (CDCl3–MeOD, 300 MHz): δ = 1.36 (s, 3 H, CH3), 1.49 (s, 3 H, CH3), 1.55 (s, 3 H, CH3), 1.57 (s, 3 H, CH3), 2.34 (s, 3 H, CH3), 4.15–4.20 (m, 1 H, H-5′), 4.45–4.55 (m, 2 H, H-6′), 4.31 (dd, J = 7.9, 1.9 Hz, 1 H, H-4′), 4.34 (dd, J = 5.0, 2.5 Hz, 1 H, H-2′), 4.65 (dd, J = 7.9, 2.6 Hz, 1 H, H-3′), 5.58 (d, J = 5.0 Hz, 1 H, H-1′′); 13C NMR (CDCl3–MeOD, 75 MHz): δ = 24.3 (CH3), 24.6 (CH3), 25.6 (CH3), 25.8 (CH3), 44.4 (C-6′), 65.6 (C-5′), 70.4 (C-2′), 70.6 (C-3′), 70.8 (C-4′), 97.3 (C-1′), 107.9, 108.7; HRMS (ESI): m/z [M + H]+ calcd for C15H25N4O5: 341.3823; found: 341.1695.
- 33 Preparation of 8a–c; General Procedure: To a solution of BuLi (2 mmol) in anhydrous THF (1.5 mL), was added a solution of the acetonitrile (4 mmol) in anhydrous THF (2.0 mL) at 0 °C under an argon atmosphere. After 5 min, a solution of azide derivative 5 (2 mmol) in anhydrous THF (2.0 mL) was added. The reaction was allowed to warm to r.t. with monitoring by TLC. Distilled water (10 mL) was then added, the mixture was extracted with EtOAc and the organic layer was dried with sodium sulfate, filtered, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel and eluted with increasing polarity gradient mixture of hexane and ethyl acetate.
- 34 4-Methyl-1-(5-amino-1-phenyl-1H-1,2,3-triazole-4-yl)ethanone (8a): Yield: 41%; white solid; mp 208.4–209.8 °C; IR (KBr): 3293 (N-H), 1664 (C=O) cm–1; 1H NMR (CDCl3, 300 MHz): δ = 2.16 (s, 3 H, CH3), 7.10 (t, J = 7.9 Hz, 1 H, H-4′), 7.30 (d, J = 7.9 Hz, 2 H, H-3′ and H-5′), 7.50 (d, J = 7.9 Hz, 2 H, H-2′ and H-6′), 7.60 (br s, 2 H, NH2); 13C NMR (CDCl3, 75 MHz): δ = 24.5 (CH3), 119.9 (C-2′ and C-6′), 124.3 (C-4′), 128.9 (C-3′ and C-5′), 137.9, 168.5; HRMS (ESI): m/z [M + H]+ calcd for C10H11N4O: 203.2200; found: 203.1021.1-[5-Amino-1-(4-chlorophenyl)-1H-1,2,3-triazole-4-yl]ethanone (8b): Yield: 30%; white solid; mp 210.7–211.2 °C; IR (KBr): 3359 (N-H), 1658 (C=O) cm–1; 1H NMR (CDCl3, 500 MHz): δ = 2.64 (m, 3 H, COCH3), 5.66 (s, 2 H, NH2), 7.49 (d, J = 7.5 Hz, 2 H, H-3′ and H-5′), 7.56 (d, J = 7.5 Hz, 2 H, H-2′ and H-6′); 13C NMR (CDCl3, 125 MHz): δ = 26.2 (CH3), 125.0 (C3′ and C-5′), 129.6 (C-5), 130.3 (C-2′ and C-6′), 132.6 (C-4′), 135.7 (C-1′), 144.2 (C-4), 193.8 (C=O); HRMS (ESI): m/z [M + H]+ calcd for C10H10ClN4O: 237.6651; found: 237.0536.1-[5-Amino-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-yl]ethanone (8c): Yield: 46%; brown solid; mp 206.4–207.8 °C; IR (KBr): 3324 (N-H), 1656 (C=O) cm–1; 1H NMR (CDCl3, 300 MHz): δ = 2.66 (s, 3 H, CH3), 3.88 (s, 3 H, OCH3), 5.54 (br s, 2 H, NH2), 7.07 (d, J = 9.0 Hz, 2 H, H-3′ and H-5′), 7.42 (d, J = 9.0 Hz, 2 H, H-2′ and H-6′); 13C NMR (CDCl3, 75 MHz): δ = 26.2 (CH3), 55.6 (OCH3), 115.3 (C-3′ and C-5′), 125.8 (C-3′ and C-5′), 129.6, 144.5, 160.5 (C=O); HRMS (ESI): m/z [M + H]+ calcd for C10H13N4O2: 233.2460; found: 233.1031.