Synlett 2009(8): 1315-1317  
DOI: 10.1055/s-0028-1216738
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Three-Component Nef-Huisgen Access to 1,2,4-Triazoles

Laurent El Kaim*, Laurence Grimaud*, Simon Wagschal
Laboratoire Chimie et Procédés, Ecole Nationale Supérieure de Techniques Avancées, 32 Boulevard Victor, 75739 Paris Cedex 15, France
Fax: +33(1)45525587; e-Mail: laurent.elkaim@ensta.fr; e-Mail: laurence.grimaud@ensta.fr;
Further Information

Publication History

Received 13 February 2009
Publication Date:
07 May 2009 (online)

Abstract

We present herein a new three-component triazole synthesis involving a Nef-Huisgen cascade. After the α-addition of acyl chlorides onto isocyanides (Nef reaction), the resulting imidoyl chloride is treated with tetrazoles under suitable activation (ZnCl2). The resulting adduct is unstable and evolves according to the Huisgen reaction.

    References and Notes

  • For general reviews on Ugi- and Passerini-based multicomponent reactions, see:
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5

Typical Procedure for 4a: Cyclohexyl isocyanide (1 mmol) and p-fluorobenzoyl chloride (1 mmol) were heated neat for 1 h in a CEM microwave at 60 ˚C (50 W) and finally dissolved in toluene (2 mL). To this solution was added ZnCl2 in THF (0.1 mL of a 1 M solution) followed by the addition of phenyl tetrazole (1 mmol, 1 equiv). The reaction mixture was then heated overnight at 80 ˚C. Hydrolysis followed by extraction and flash column chromatography afforded 4a as a yellow oil (280 mg, 79%).
Spectroscopic Data for Triazole 4a: 1H NMR (400 MHz, CDCl3): d = 8.35 (dd, J H-H = 8.3, J H-F = 5.6 Hz, 2H), 7.65-7.35 (m, 5H), 7.21 (t, J H-H = J H-F = 8.3 Hz, 2H), 4.33 (tt,
J = 12.3, 3.7 Hz, 1H), 2.15 (q, J = 11.8 Hz, 2H), 1.92 (d,
J = 11.8 Hz, 2H), 1.83 (d, J = 11.8 Hz, 2H), 1.65 (d, J = 10.6 Hz, 1H), 1.34-1.15 (m, 3H). 13C NMR (100.6 MHz, CDCl3): d = 183.6, 166.8 (d, J C-F = 256.1 Hz), 157.5, 151.9, 134.4 (d, JC-F = 9.5 Hz), 133.5 (d, J C-F = 2.2 Hz), 131.1, 130.1, 129.3, 128.0, 116.1 (d, J C-F = 22.0 Hz), 59.2, 32.6, 26.3, 25.1.IR (thin film): 2933, 2857, 2360, 1663, 1597, 1506, 1440, 1307, 1235, 1157 cm. HRMS: m/z calcd for C21H20FN3O: 349.1590; found: 349.1601.