Efficient Synthesis of 5-Fluoroalkylated 1H-1,2,3-Triazoles and Application of the Bromodifluoromethylated Triazole to Prepare New gem-Difluorinated Triazole Compounds

Abstract

A series of 5-fluoroalkylated 1H-1,2,3-triazoles was prepared in good yield by the regiospecific 1,3-dipolar cycloaddition reaction of the (Z) ethyl 3-fluoroalkyl-3-pyrrolidino-acrylates with aryl or benzyl azides. In the cases of benzyl azides, addition of Na₂CO₃ was crucial for a high yield of the triazoles. The tetrakis(dimethylamino)ethylene (TDAE) promoted reaction of the bromo-difluoromethylated 1H-1,2,3-triazole with aldehyde afforded a new class of novel gem-difluorinated triazole compounds.

acrylates - 1,3-dipolar cycloaddition - fluoroalkylated 1H-1,2,3-triazole - tetrakis(dimethylamino)ethylene - gem-difluorinated compound

References

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The analytical and spectroscopic data for triazole 3aa was demonstrated as an example. 5-Chlorodifluoromethyl-1-phenyl-1 H -1,2,3-triazole-4-carboxylic Acid, Ethyl Ester(3aa): Mp: 69.5-70.5 °C. [Found: C, 47.80; H, 3.35; N, 14.24. C₁₂H₁₀ClF₂N₃O₂ requires C, 47.78; H, 3.34; N, 13.93%]. IR(film): 2982, 1723, 1593, 1560, 1497, 1375, 1296, 1254, 1238, 1153, 1094, 1058, 1008, 906, 771 cm^-1. ¹H NMR (60 MHz, CDCl₃): δ = 1.47 (3 H, t, J = 7.0 Hz), 4.52 (2 H, q, J = 7.0 Hz), 7.34-7.74 (5 H, m). ¹⁹F NMR (56.4 MHz, CDCl₃): δ = -44.5; EI-MS: m/z (%) = 302/304 (10/3) [M⁺ + 1], 256/258 (12/4), 245/247 (10/3), 189 (42), 170 (33), 144 (19), 77 (100) [Ph⁺].

21

Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publication numbers CCDC 196350. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [Fax:[phone] or e-mail: [e-mail]. ac.uk].

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25

5-(1,1-Difluoro-2-hydroxy-2-phenyl-ethyl)-1-pheny-l-1 H -1,2,3-triazole-4-carboxylic Acid, Ethyl Ester(7a): Mp: 146.0-148.0 °C. Found: C, 61.41; H, 4.78; N, 10.97. C₁₉H₁₇F₂N₃O₃ requires C, 61.12; H, 4.59; N, 11.25. IR(film): 3445, 3065, 2984, 1778, 1717, 1595, 1546, 1497, 1249, 1231, 1170, 1077, 1014, 766, 738, 693 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.51 (3 H, t, J = 7.2 Hz), 4.01 (1 H, d, J = 3.9 Hz), 4.55 (2 H, q, J = 7.2 Hz), 5.63 (1 H, ddd, J = 12.7, 8.7, 3.9 Hz), 6.89-7.49 (10 H, m). ¹⁹F NMR (282 MHz, CDCl₃): δ = -100.3 (AB-d, J = 273.0, 12.7, 8.7 Hz); EI-MS: m/z (%) = 373 (8) [M⁺], 353 (15), 328 (1), 300 (3), 281 (1), 104 (25), 77 (100) [Ph⁺], 51 (20).