Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2020; 31(02): 175-178
DOI: 10.1055/s-0039-1691526
DOI: 10.1055/s-0039-1691526
letter
One-Pot, Metal- and Azide-Free Synthesis of 1,2,3-Triazoles from α-Ketoacetals and Amines
Further Information
Publication History
Received: 16 October 2019
Accepted after revision: 19 November 2019
Publication Date:
03 December 2019 (online)
![](https://www.thieme-connect.de/media/synlett/202002/lookinside/thumbnails/st-2019-v0564-l_10-1055_s-0039-1691526-1.jpg)
Abstract
An efficient one-pot two-step synthesis of 1,4-disubstituted 1,2,3-triazoles from α-ketoacetals and amines is presented. The method does not use metals, azides, or oxidants, and is compatible with a variety of functional groups, including heterocycles, esters, nitriles, and carbamates.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691526.
- Supporting Information
-
References and Notes
- 1 Dheer D, Singh V, Shankar R. Bioorg. Chem. 2017; 71: 30
- 2a Huisgen R, Knorr R, Moebius L, Szeimies G. Chem. Ber. 1965; 98: 4014
- 2b Huisgen R, Szeimies G, Moebius L. Chem. Ber. 1967; 100: 2494
- 3 Kolb HC, Finn MG, Sharpless KB. Angew. Chem. Int. Ed. 2001; 40: 2004
- 4a Tornøe CW, Christensen C, Meldal M. J. Org. Chem. 2002; 67: 3057
- 4b Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
- 5a Zhang L, Chen X, Xue P, Sun HH. Y, Williams ID, Sharpless KB, Fokin VV, Jia G. J. Am. Chem. Soc. 2005; 127: 15998
- 5b Ding S, Jia G, Sun J. Angew. Chem. Int. Ed. 2014; 53: 1877
- 5c Song W, Zheng N. Org. Lett. 2017; 19: 6200
- 6 Ahmed M, Razaq H, Faisal M, Siyal AN, Haider A. Synth. Commun. 2017; 47: 1193
- 7a Sakai K, Hida N, Kondo K. Bull. Chem. Soc. Jpn. 1986; 59: 179
- 7b Harada K, Oda M, Matsushita A, Shirai M. Heterocycles 1998; 48: 695
- 8 van Berkel SS, Brauch S, Gabriel L, Henze M, Stark S, Vasilev D, Wessjohann LA, Abbas M, Westermann B. Angew. Chem. Int. Ed. 2012; 51: 5343
- 9 Barluenga J, Llavona L, Concellón JM, Yus M. J. Chem. Soc., Perkin Trans. 1 1991; 297
- 10 Anthore-Dalion L, Zard SZ. Org. Lett. 2017; 19: 5545
- 11 Cho E, Kim M, Jayaraman A, Kim J, Lee S. Eur. J. Org. Chem. 2018; 781
- 12a Chen Z, Yan Q, Yi H, Liu Z, Lei A, Zhang Y. Chem. Eur. J. 2014; 20: 13692
- 12b Chen Z, Yan Q, Yi H, Liu Z, Lei A, Zhang Y. Chem. Eur. J. 2014; 20: 17635
- 13a Cai Z.-J, Lu X.-M, Zi Y, Yang C, Shen L.-J, Li J, Wang S.-Y, Ji S.-J. Org. Lett. 2014; 16: 5108
- 13b Bai H.-W, Cai Z.-J, Wang S.-Y, Ji S.-J. Org. Lett. 2015; 17: 2898
- 14 Zhou Q, Fu Z, Yu L, Wang J. Asian J. Org. Chem. 2019; 8: 646
- 15 Shu W.-M, Zhang X.-F, Zhang X.-X, Li M, Wang A.-J, Wu A.-X. J. Org. Chem. 2019; 84: 14919
- 16 Deng L, Cao X, Liu Y, Wan J.-P. J. Org. Chem. 2019; 84: 14179
- 17 Zhang D, Fan Y, Yan Z, Nie Y, Xiong X, Gao L. Green Chem. 2019; 21: 4211
- 18 Yang L, Wu Y, Yang Y, Wen C, Wan J.-P. Beilstein J. Org. Chem. 2018; 14: 2348
- 19 Cao S, Liu Y, Hu C, Wen C, Wan J.-P. ChemCatChem 2018; 10: 5021
- 20 Huang W, Zhu C, Li M, Yu Y, Wu W, Tu Z, Jiang H. Adv. Synth. Catal. 2018; 360: 3117
- 21a Ayala-Mata F, Barrera-Mendoza C, Jiménez-Vázquez HA, Vargas-Díaz E, Zepeda LG. Molecules 2012; 17: 13864
- 21b Adamczyk M, Johnson DD, Mattingly PG, Pan Y, Reddy RE. Synth. Commun. 2002; 32: 3199
- 21c Smith DS, Winnick J, Ding Y, Bottomley LA. Electrochim. Acta 1997; 43: 335
- 21d El-Wareth A, Sarhan AO, Hoffmann HM. R. J. Prakt. Chem./Chem.-Ztg. 1997; 339: 390
- 21e Tamura Y, Annoura H, Fuji M, Yoshida T, Takeuchi R, Fujioka H. Chem. Pharm. Bull. 1987; 35: 4736
- 22 Methyl 4-(4-Methyl-1H-1,2,3-triazol-1-yl)benzoate (3h); Typical ProcedureTsNHNH2 (308 mg, 1.65 mmol) was added to a solution of 1,1-dimethoxypropan-2-one (195 mg, 1.65 mmol) in DMSO (2 mL), and the mixture was stirred for 1 h at r.t. Methyl 4-aminobenzoate (262 mg, 1.74 mmol) was then added and the mixture was heated at 80 °C for 4 h, then cooled. The solution was filtered and purified by supercritical fluid chromatography (Princeton HA-Morpholine column) to give a white solid; yield: 198 mg (55%).1H NMR (400 MHz, DMSO-d 6): δ = 8.66 (s, 1 H), 8.19–8.10 (m, 2 H), 8.08–7.98 (m, 2 H), 3.89 (s, 3 H), 2.34 (s, 3 H). 13C NMR (101 MHz, DMSO-d 6): δ = 165.3, 143.6, 139.9, 130.9, 128.9, 120.5, 119.4, 52.3, 10.4. HRMS (ESI): m/z [M + H]+ Calcd for C11H12N3O2: 218.0924; found: 218.0930.
- 23 Arunachalam PN, Kuppusamy P, Ganesan S, Krishnamoorthy S, Nimje RY, Jarugu LB, Kanikahalli Chikkananjaiah N, Anki Reddy C, Anjanappa P, Botlagunta M, Vanteru S, Maddala N, Shankar M, Nair S, Hynes Jr J, Santella III JB, Carter PH, Rampulla R, Vetrichelvan M, Gupta A, Gupta AK, Mathur A. Org. Process Res. Dev. 2019; 23: 912
- 24 Tiecco M, Testaferri L, Tingoli M, Bartoli D. J. Org. Chem. 1990; 55: 4523
- 25 Methyl 3-{1-[6-Chloro-4-(isopropylamino)pyridin-3-yl]-1H-1,2,3-triazol-4-yl}propanoate (7)To a solution of TsNHNH2 (98 mg, 0.53 mmol) were added ester 5 (100 mg, 0.55 mmol), prepared according to ref. 24, and diamine 6 (100 mg, 0.53 mmol) in DMSO (1 mL), and the mixture was heated at 80 °C for 6 h, then cooled. The resulting solution was purified by reverse-phase chromatography [Teledyne Isco ACCQPrep; Luna Omega 5μm Polar C18 column (250 × 30 mm), gradient elution: H2O–HOAc/MeCN]. The pure fractions were combined, and MeCN was removed by evaporation under reduced pressure. The resulting aqueous mixture was frozen and lyophilized to give a white solid; yield: 91 mg (55%).1H NMR (400 MHz, DMSO-d 6): δ = 8.30 (s, 1 H), 8.05 (s, 1 H), 6.91 (s, 1 H), 6.41 (br d, J = 7.9 Hz, 1 H), 3.86–3.77 (m, 1 H), 3.62 (s, 3 H), 3.03–2.96 (m, 2 H), 2.80–2.73 (m, 2 H), 1.14 (d, J = 6.4 Hz, 6 H). 13C NMR (101 MHz, DMSO-d 6): δ = 172.4, 151.3, 148.2, 145.9, 144.5, 123.5, 119.3, 105.2, 51.4, 43.4, 32.4, 21.6, 20.5. HRMS (ESI): m/z [M + H]+ Calcd for C14H19ClN5O2: 324.1222; found: 324.1223.