4-Aryl-NH-1,2,3-Triazoles via Multicomponent Reaction of Aldehydes, Nitroalkanes, and Sodium Azide

Abstract

4-Aryl-NH-1,2,3-triazoles are valuable compounds in organic chemistry and pharmaceutical chemistry. In this paper, we describe a novel multicomponent reaction of aldehydes, nitroalkanes, and sodium azide for the synthesis of 4-aryl-NH-1,2,3-triazoles. In this transformation, it was found that both the slow addition of nitroalkane and the presence of NaHSO₃/Na₂SO₃ are advantageous to promote the reaction results. Additionally, a series of aldehydes and nitro compounds were investigated.

Key words

NH-1,2,3-triazole - multicomponent reaction - aldehyde - nitroalkane - sodium azide

• References and Notes

• 1a Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G, Genazzani AA. Med. Res. Rev. 2008; 28: 278
• 1b Giffin MJ, Heaslet H, Brik A, Lin Y.-C, Cauvi G, Wong C.-H, McRee DE, Elder JH, Stout CD, Torbett BE. J. Med. Chem. 2008; 51: 6263
• 1c Komine T, Kojoma A, Asahina Y, Saito T, Takano H, Shibue T, Fukuda Y. J. Med. Chem. 2008; 51: 6558
• 1d Petchprayoon C, Suwanborirux K, Miller R, Sakata T, Marriott G. J. Nat. Prod. 2005; 68: 157
• 1e Tome AC In Science of Synthesis . Vol. 13. Storr RC, Gilchrist TL. Thieme; New York: 2004: 415
• 1f Kolb HC, Sharpless KB. Drug Discovery Today 2003; 8: 1128
• 1g Baures PW. Org. Lett. 1999; 1: 249
• 1h Whiting M, Muldoon J, Lin Y.-C, Silverman SM, Lindstrom W, Olson AJ, Kolb HC, Finn MG, Sharpless KB, Elder JH, Fokin VV. Angew. Chem. Int. Ed. 2006; 45: 1435
• 1i Lewis WG, Green LG, Grynszpan F, Radic Z, Carlier PR, Taylor P, Finn MG, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 1053
• 1j Tron GC, Pirali T, Billington RA, Canonico PL, Sorba G, Genazzani AA. Med. Res. Rev. 2008; 28: 278
• 2a Kallander LS, Lu Q, Chen W, Tomaszek T, Yang G, Tew D, Meek TD, Hofmann GA, Schulz-Pritchard CK, Smith WW, Janson CA, Ryan MD, Zhang G.-F, Johanson KO, Kirkpatrick RB, Ho TF, Fisher PW, Mattern MR, Johnson RK, Hansbury MJ, Winkler JD, Ward KW, Veber DF, Thompson SK. J. Med. Chem. 2005; 48: 5644
• 2b Röhrig UF, Majjigapu SR, Grosdidier A, Bron S, Stroobant V, Pilotte L, Colau D, Vogel P, Van den Eynde BJ, Zoete V, Michielin O. J. Med. Chem. 2012; 55: 5270
• 2c Zhao Y, Zhou Y, O’Boyle KM, Murphy PV. Bioorg. Med. Chem. 2008; 16: 6333
• 2d Röhrig UF, Awad L, Grosdidier A, Larrieu P, Stroobant V, Colau D, Cerundolo V, Simpson AJ. G, Vogel P, Van den Eynde BJ, Zoete V, Michielin O. J. Med. Chem. 2010; 53: 1172
• 2e Genin MJ, Allwine DA, Anderson DJ, Barbachyn MR, Emmert DE, Garmon SA, Graber DR, Grega KC, Hester JB, Hutchinson DK, Morris J, Reischer RJ, Ford CW, Zurenko GE, Hamel JC, Schaadt RD, Stapert D, Yagi BH. J. Med. Chem. 2000; 43: 953
• 2f Huang Q, Zheng M, Yang S, Kuang C, Yu C, Yang Q. Eur. J. Med. Chem. 2011; 46: 5680
• 3a Liu Y, Yan W, Chen Y, Petersen JL, Shi X. Org. Lett. 2008; 10: 5389
• 3b Ueda S, Su M, Buchwald SL. Angew. Chem. Int. Ed. 2011; 50: 8944
• 3c Wen J, Zhu L.-L, Bi Q.-W, Shen Z.-Q, Li X.-X, Li X, Wang Z, Chen Z. Chem. Eur. J. 2014; 20: 974
• 3d Oh S, Shin W.-S, Ham J, Lee S. Bioorg. Med. Chem. Lett. 2010; 20: 4112
• 4a Jin T, Kamijo S, Yamamoto Y. Eur. J. Org. Chem. 2004; 3789
• 4b Alonso F, Moglie Y, Radivoy G, Yus M. J. Org. Chem. 2013; 78: 5031
• 4c Loren JC, Krasiński A, Fokin VV, Sharpless KB. Synlett 2005; 2847
• 4d Yap AH, Weinreb SM. Tetrahedron Lett. 2006; 47: 3035
• 4e Kalisiak J, Sharpless KB, Fokin VV. Org. Lett. 2008; 10: 3171
• 5a Barluenga J, Valdés C, Beltrán G, Escribano M, Aznar F. Angew. Chem. Int. Ed. 2006; 45: 6893
• 5b Jiang Y, Kuang C, Yang Q. Synthesis 2010; 4256
• 5c Wang X, Kuang C, Yang Q. Eur. J. Org. Chem. 2012; 424
• 5d Zhang W, Kuang C, Yang Q. Synthesis 2010; 283
• 6a Quan X.-J, Ren Z.-H, Wang Y.-Y, Guan Z.-H. Org. Lett. 2014; 16: 5728
• 6b Amantini D, Fringuelli F, Piermatti O, Pizzo F, Zunino E, Vaccaro L. J. Org. Chem. 2005; 70: 6526
• 6c Quiclet-Sire B. Zard S. Z. 2005; 3319
• 6d Gao Y, Lam Y. Org. Lett. 2006; 8: 3283
• 6e Arigela RK, Samala S, Mahar R, Shukla SK, Kundu B. J. Org. Chem. 2013; 78: 10476
• 6f Jia F.-C, Xu C, Zhou Z.-W, Cai Q, Li D.-K, Wu A.-X. Org. Lett. 2015; 17: 2820
• 6g Anisimova NA, Berestovitskaya VM, Berkova GA, Makarova NG. Russ. J. Org. Chem. 2007; 43: 652
• 7a Banert K. Chem. Ber. 1989; 122: 911
• 7b Loren JC, Sharpless KB. Synthesis 2005; 1514
• 7c Koszytkowska-Stawińska M, Sas W. Tetrahedron 2013; 69: 2619
• 8a Augustine JK, Boodappaa C, Venkatachaliaha S. Org. Biomol. Chem. 2014; 12: 2280
• 8b He Y, Sun E, Zhao Y, Wu Y. Tetrahedron Lett. 2014; 55: 111

For recent reviews, see:
• 9a Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
• 9b Armstrong RW, Combs AP, Tempest PA, Brown DA, Keating TA. Acc. Chem. Res. 1996; 29: 123
• 9c Zhu J, Bienayme H. Multicomponent Reactions . Wiley-VCH; Weinheim: 2005
• 9d Bienaymé H, Hulme C, Oddon G, Schmitt P. Chem. Eur. J. 2000; 6: 3321
• 9e Dömling A. Chem. Rev. 2006; 106: 17
• 9f Alvim HG. O, da Silva Júnior EN, Neto BA. D. RSC Adv. 2014; 4: 54282
• 9g Cioc RC, Ruijter E, Orru RV. A. Green Chem. 2014; 16: 2958

For recent reports and reviews, see:
• 10a Hassan S, Müller TJ. J. Adv. Synth. Catal. 2015; 357: 617
• 10b Li J, Wang D, Zhang Y, Li J, Chen B. Org. Lett. 2009; 11: 3024
• 10c Kamijo S, Jin T, Huo Z, Yamamoto Y. J. Am. Chem. Soc. 2003; 125: 7786
• 10d Yan Z.-Y, Zhao Y.-B, Fan M.-J, Liu W.-M, Liang Y.-M. Tetrahedron 2005; 61: 9331
• 10e Li N, Wang D, Li J, Shi W, Li C, Chen B. Tetrahedron Lett. 2011; 52: 980
• 11a Sengupta S, Duan H, Lu W, Petersen JL, Shi X. Org. Lett. 2008; 10: 1493
• 11b Chai H, Guo R, Yin W, Cheng L, Liu R, Chu C. ACS Comb. Sci. 2015; 17: 147
• 11c Thomas J, Parekh N, Dehaen W. Angew. Chem. Int. Ed. 2014; 53: 10155
• 12a Yan G, Borah AJ, Wang L. Org. Biomol. Chem. 2014; 12: 6049
• 12b Fioravanti S, Pellacani L, Tardella PA, Vergari MC. Org. Lett. 2008; 10: 1449
• 13a Wu L.-Y, Xie Y.-X, Chen Z.-S, Niu Y.-N, Liang Y.-M. Synlett 2009; 1453
• 13b Wu L, Chen Y, Tang M, Song X, Chen G, Song X, Lin Q. Synlett 2012; 23: 1529
• 13c Wu L, Chen Y, Luo J, Sun Q, Peng M, Lin Q. Tetrahedon Lett. 2014; 55: 3847
• 13d Wu L, Guo S, Wang X, Guo Z, Yao G, Lin Q, Wu M. Tetrahedron Lett. 2015; 56: 2145
• 14a Alcántara M.-PD, Escribano FC, Gómez-Sánchez A, Diánez MJ, Estrada MD, López-Castro A, Pérez-Garrido S. Synthesis 1996; 64
• 14b Ballini R, Bosica G, Fiorini D. Synthesis 2004; 1938
• 14c Rabalakos C, Wulff WD. Synlett 2008; 2826
• 15 To a 10 mL round-bottom bottle with a condenser was added benzaldehyde (2.0 mmol), NaN₃ (8.0 mmol), NaHSO₃ (2 mmol), Na₂SO₃ (2 mmol), and DMSO (4 mL). The top of the condenser was connected to an aq NaOH (1 M) solution via a gas bubbler to trap off any volatile HN₃. This reaction mixture was heated at 110 °C under argon atmosphere. Then, MeNO₂ (4.0 mmol) in DMSO (2 mL) was added by a syringe pump over 2 h; after added completely, the mixture was heated for another 3 h. The mixture was cooled to r.t. and poured in to 40 mL H₂O, and then extracted with EtOAc (40 mL). The combined organic phase was washed by H₂O (3 × 40 mL) and sat. brine and then dried over anhydrous Na₂SO₄. The solvent was removed under reduced pressure, and the crude reaction mixture was purified by flash silica gel chromatography with PE–EtOAc as an eluent to give the desired product 3a; white solid; mp 143–145 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 15.14 (br, 1 H), 8.33 (br, 1 H), 7.89–7.82 (m, 2 H), 7.47–7.42 (m, 2 H), 7.36 (t, J = 7.2 Hz, 1 H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 128.9, 128.1, 125.6 ppm. IR (KBr): 3158, 2956, 1653, 1457, 1079, 764 cm^–1. ESI-HRMS: m/z [M + H]⁺ calcd for C₈H₈N₃: 146.0718; found: 146.0710. Caution! Sodium azide is a potentially explosive and toxic compound. Meanwhile, treatment of sodium azide with strong acids gives hydrazoic acid, which is also extremely toxic. In the reaction, hydrazoic acid could be formed, and hydrazoic acid should be washed off by water before evaporating on rotovap. Meanwhile, all procedures including the extraction and the evaporation should be performed in a chemical fume hood and avoid contact with strong acids.