Synlett 2014; 25(17): 2480-2484
DOI: 10.1055/s-0034-1379010
letter
© Georg Thieme Verlag Stuttgart · New York

Regiospecific Synthesis of N2-Aryl 1,2,3-Triazoles from 2,5-Disubstituted Tetrazoles via Photochemically Generated Nitrile Imine Intermediates

Sam Stewart
a  GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK   Email: [email protected]
,
Robert Harris*
a  GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK   Email: [email protected]
,
Craig Jamieson*
b  University of Strathclyde, Department of Pure and Applied Chemistry, Thomas Graham Building, 295 Cathedral Street, Glasgow, G1 1XL, UK   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 24 June 2014

Accepted after revision: 31 July 2014

Publication Date:
08 September 2014 (online)


Abstract

The synthesis of N2-aryl 1,2,3-triazoles from 2,5-disubstituted tetrazoles was achieved under photochemical conditions. This simple and mild one-step reaction provides regiospecific access to 2,4,5-substituted 1,2,3-triazoles via a nitrile imine intermediate. Syntheses of alkyl and heterocylic derivatives were also investigated.

Supporting Information

 
  • References and Notes

  • 1 Hadd MA, Nichelson BJ, Zhu Z. WO 2005/000841A1, 2005
  • 2 Hou D, Alam S, Kuan T, Ramanathan M, Lin T, Hung M. Bioorg. Med. Chem. Lett. 2009; 19: 1022
  • 3 Brockunier LL, Parmee ER, Ok HO, Candelore MR, Cascieri MA, Colwell LF, Deng L, Feeney WP, Forrest MJ, Hom GJ, Macintyre DE, Tota L, Wyvratt MJ, Fisher MH, Weber AE. Bioorg. Med. Chem. Lett. 2000; 10: 2111
  • 4 Yan W, Wang Q, Lin Q, Li M, Petersen JL, Shi X. Chem. Eur. J. 2011; 17: 5011
    • 5a Maliakal A, Lem G, Turro NJ, Ravichandran R, Suhadolnik JC, DeBellis AD, Wood MG, Lau JJ. Phys. Chem. A 2002; 106: 7680
    • 5b Heller HJ, Blatttmann HR. Pure Appl. Chem. 1973; 36: 141
  • 6 Liu Y, Yan W, Chen Y, Petersen JL, Shi X. Org. Lett. 2008; 10: 5389
  • 7 Ueda S, Su M, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 8944
  • 8 Zhang Y, Wang D, Wang W, Gao T, Wang L, Li J, Huang G, Chen B. Synlett 2010; 1617
  • 9 Zhang Y, Li X, Li J, Chen J, Meng X, Zhao M, Chen B. Org. Lett. 2012; 14: 26
  • 10 Liu X, Li X, Chen Y, Wang D, Chen J, Chen B. Asian J. Org. Chem. 2013; 212
  • 11 Sukumaran KB, Satish S, George MV. Tetrahedron 1974; 30: 445
  • 12 Butler R, O’Shea D. J. Chem. Res. 1994; 350
  • 13 Butler RN, Hanniffy JM, Stephens JC, Burke L. J. Org. Chem. 2008; 73: 1354
  • 14 Guru MM, Punniyamurthy T. J. Org. Chem. 2012; 77: 5063
  • 15 Wang Y, Vera CI. R, Lin Q. Org. Lett. 2007; 9: 4155
  • 16 Wang Y, Song W, Hu WJ, Lin Q. Angew. Chem. Int. Ed. 2009; 48: 5330
  • 17 Meier H, Heinzelmann W, Heimgartner H. Chimia 1980; 34: 504
  • 18 Claus P, Doppler T, Gakis N, Georgarakis M, Giezendanner H, Gilgen P, Heimgartner H, Jackson B, Märky M, Narasimhan NS, Rosenkranz HJ, Wunderli A, Hansen H.-J, Schmid H. Pure Appl. Chem. 1973; 33: 339
  • 19 Li Y, Gao L.-X, Han F.-S. Chem. Commun. 2012; 48: 2719
    • 20a Henderson RK, Jiménez-González C, Constable DJ. C, Alston SR, Inglis GG, Fisher G, Sherwood J, Binks SP, Curzons AD. Green Chem. 2011; 13: 854
    • 20b Pace V, Hoyos P, Castoldi L, Domínguez de María P, Alcántara AR. ChemSusChem 2012; 5: 1369
    • 20c Yilgor E, Ekin Atilla G, Ekin A, Kurt P, Yilgor I. Polymer 2003; 44: 7787
  • 21 Meier H, Heinzelmann W, Heimgartner H. Helv. Chim. Acta 1985; 68: 1283
  • 22 Abu Thaher B, Zahra J, El-Abadelah MM, Voelter W. Z. Naturforsch., B: J. Chem. Sci. 2004; 59: 930
  • 23 Böhm VP. W, Herrmann WA. Angew. Chem. Int. Ed. 2000; 39: 4036
  • 24 Molteni G, Orlandi M, Broggini G. J. Chem. Soc., Perkin Trans. 1 2000; 3742
  • 25 Wentrup C, Benedikt J. J. Org. Chem. 1980; 45: 1407
  • 26 Wentrup C, Damerius A, Reichen W. J. Org. Chem. 1978; 43: 2037
  • 27 Patel H, Vyas K, Pandey S, Fernandes P. Tetrahedron 1996; 52: 661
  • 28 Representative Example for the Preparation of 2,5-Diaryl Tetrazoles: 5-Phenyl-2-(p-tolyl)-2H-tetrazole (5f) A solution of p-tolyl boronic acid (1.86 g, 13.7 mmol), 5-phenyl tetrazole (1.00 g, 6.84 mmol), and Cu2O (5 mol%, 0.049 g, 0.342 mmol) in DMSO (30 mL) was stirred under O2 (1 atm) at 110 °C for 6 h. The reaction mixture was allowed to cool, diluted with EtOAc (200 mL) and washed successively with 1 M HCl aq solution (30 mL) and brine (30 mL) three times. The organic phase was separated, dried, and concentrated in vacuo. Purification by flash column chromatography (Si, 50 g, 0–10% EtOAc–cyclohexane, 60 min) gave 5-phenyl-2-(p-tolyl)-2H-tetrazole 5f (1.51 g, 93%) as a white solid; mp 103–104 °C. IR: 1507, 1448, 1212, 1012 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.26 (dd, J = 2.0, 8.1 Hz, 2 H), 8.08 (d, J = 8.6 Hz, 2 H), 7.57–7.47 (m, 3 H), 7.38 (d, J = 8.6 Hz, 2 H), 2.46 (s, 3 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 165.1, 139.9, 134.8, 130.5, 130.2, 128.9, 127.3, 127.0, 120.0, 119.8, 77.3, 77.2, 77.0, 76.7, 21.2 ppm. HRMS (ESI+): m/z calcd for C14H13N4: 237.1135; found: 237.1128. Representative Example for the Preparation of 2,4,5-Trisubstituted 1,2,3-Triazoles: 4,5-Diphenyl-2-(p-tolyl)-2H-1,2,3-triazole (9f) A solution of 5-phenyl-2-(p-tolyl)-2H-tetrazole 5f (200 mg, 0.85 mmol) in 2-PrOH–2-MeTHF (1:1, 10 mL) was stirred under irradiation with a UVB lamp (270–330 nm) for 19 h. The reaction mixture was concentrated in vacuo and the residue purified by reverse-phase chromatography (Si C18, 50–95% MeCN–H2O, HCO2H modifier, 30 min) to give 4,5-diphenyl-2-(p-tolyl)-2H-1,2,3-triazole 9f (62 mg, 47%) as a brown gum. IR: 1510, 1441, 1268 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J = 8.6 Hz, 2 H), 7.72–7.65 (m, 4 H), 7.43 (dd, J = 1.9, 4.9 Hz, 6 H), 7.33 (d, J = 8.6 Hz, 2 H), 2.45 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ = 145.7, 137.6, 137.3, 130.9, 129.8, 128.6, 128.6, 128.5, 127.1, 118.7, 21.1. HRMS (ESI+): m/z calcd for C21H18N3: 312.1495; found: 312.1496.