1. Patent Search
  2. Details

Process for the preparation of azidoperfluoroalkanes and N-polyfluoroalkyl azides

10590091 · 2020-03-17

Assignee

Inventors

Cpc classification

International classification

Abstract

Process for the preparation of azidoperfluoroalkanes and azidopolyfluoroalkanes of general formula R.sub.FN.sub.3, where R.sub.F is chosen from a group containing C.sub.nF.sub.2n+1, C.sub.nF.sub.xH.sub.2n+1x, C.sub.nF.sub.xX.sub.2n+1x or R.sup.1CF.sub.2CF.sub.2, where n is an integer in the range of 1 to 10, x is an integer in the range of 2 to 20, X is Cl, Br, or I, R.sup.1 is C.sub.1-10 alkyl, ArO, ArS, imidazolyl, benzimidazolyl, or pyrazolyl and Ar is phenyl or substituted phenyl, by the reaction of electrophilic azidation reagent of general formula R.sup.2N.sub.3, where R.sup.2 is n-C.sub.4F.sub.9SO.sub.2, ArSO.sub.2, Br, I, with synthetic equivalent of polyfluoroalkylated carbanion of general formula [R.sub.F].sup..

Claims

1. A method for preparation of azidoperfluoroalkanes and azidopolyfluoroalkanes of formula R.sub.FN.sub.3, wherein R.sub.F is selected from the group consisting of C.sub.nF.sub.2n+1, C.sub.nF.sub.xH.sub.2n+1x, C.sub.nF.sub.xX.sub.2n+1x or R.sup.1CF.sub.2CF.sub.2, wherein n is an integer in the interval from 1 to 10, x is an integer in the interval from 2 to 20 and X is Cl, Br, or I, R.sup.1 is selected from the group consisting of C.sub.1-10 alkyl, ArO, ArS, imidazolyl, benzimidazolyl, or pyrazolyl and Ar is phenyl or substituted phenyl, said process having the following steps (A) generation of a synthetic equivalent of polyfluoroalkyl carbanion, said synthetic equivalent having the formula [R.sub.F].sup., by a method selected from: a) activation of trialkyl(polyfluoroalkyl)silane of general formula R.sup.3.sub.3SiR.sub.F, wherein R.sup.3 is C.sub.1-5 alkyl, with a Lewis base which is selected from the group consisting of potassium fluoride, cesium fluoride, tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium carbonate, potassium carbonate, potassium phosphate, sodium acetate, potassium acetate, tetrabutylammonium acetate; b) reaction of polyfluoroalkane of general formula R.sub.FH with a base which is selected from a group consisting of methyllithium, butyllithium, phenyllithium, Grignard reagent of general formula R.sup.3MgX, wherein R.sup.3 is C.sub.1-5 alkyl, and complexes of these compounds with LiCl; or c) reaction of halopolyfluoroalkane of general formula R.sub.FBr or R.sub.FI with metalation reagents, which are selected from a group consisting of methyllithium, butyllithium, Grignard reagent of general formula R.sup.3MgX, wherein R.sup.3 is C.sub.1-5 alkyl, and complexes of these compounds with LiCl, at a temperature in the range from 78 C., or from the melting point of the reaction mixture, to +60 C., and (B) reaction of an electrophilic azidation reagent of general formula R.sup.2N.sub.3, wherein R.sup.2 is selected from the group consisting of n-C.sub.4F.sub.9SO.sub.2, ArSO.sub.2, Br, and I, wherein Ar is phenyl or substituted phenyl, with the synthetic equivalent of polyfluoroalkyl carbanion of general formula [R.sub.F].sup. generated in step (A).

2. A method for preparation of N-perfluoroalkyl- or N-polyfluoroalkyl-substituted triazoles of formula 1 ##STR00007## wherein R.sub.F is selected from the group consisting of C.sub.nF.sub.2n+1, C.sub.nF.sub.xH.sub.2n+1x, C.sub.nF.sub.xX.sub.2n+1x or R.sup.1CF.sub.2CF.sub.2, wherein n is an integer in the interval from 1 to 10, x is an integer in the interval from 2 to 20 and X is Cl, Br, or I, R.sup.1 is selected from the group consisting of C.sub.1-10 alkyl, ArO, ArS, imidazolyl, benzimidazolyl, or pyrazolyl and Ar is phenyl or substituted phenyl, R.sup.4 is selected from a group consisting of C.sub.1-10 alkyl, XCH.sub.2CH.sub.2, COOR.sup.3, C(CH.sub.3).sub.2OH, benzyloxy-C.sub.1-4-alkyl, pyridyl, phenyl, and pyridyl or phenyl substituted by a group selected from C.sub.1-10 alkyl, F, Cl, Br, I, OR.sup.3, NO.sub.2, NH.sub.2, CF.sub.3, wherein R.sup.3 is C.sub.1-5 alkyl, by performing the steps of: (A) generation of a synthetic equivalent of polyfluoroalkyl carbanion, said synthetic equivalent having the formula [R.sub.F].sup., by a method selected from: a) activation of trialkyl(polyfluoroalkyl)silane of general formula R.sup.3.sub.3SiR.sub.F, wherein R.sup.3 is C.sub.1-5 alkyl, with a Lewis base which is selected from the group consisting of potassium fluoride, cesium fluoride, tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium carbonate, potassium carbonate, potassium phosphate, sodium acetate, potassium acetate, tetrabutylammonium acetate; b) reaction of polyfluoroalkane of general formula R.sub.FH with a base which is selected from a group consisting of methyllithium, butyllithium, phenyllithium, Grignard reagent of general formula R.sup.3MgX, wherein R.sup.3 is C.sub.1-5 alkyl, and complexes of these compounds with LiCl; or c) reaction of halopolyfluoroalkane of general formula R.sub.FBr or R.sub.FI with metalation reagents, which are selected from a group consisting of methyllithium, butyllithium, Grignard reagent of general formula R.sup.3MgX, wherein R.sup.3 is C.sub.1-5 alkyl, and complexes of these compounds with LiCl, at a temperature in the range from 78 C., or from the melting point of the reaction mixture, to +60 C., and (B) reaction of an electrophilic azidation reagent of general formula R.sup.2N.sub.3, wherein R.sup.2 is selected from the group consisting of n-C.sub.4F.sub.9SO.sub.2, ArSO.sub.2, Br, and I, wherein Ar is phenyl or substituted phenyl, with the synthetic equivalent of polyfluoroalkyl carbanion of general formula [R.sub.F].sup. generated in step (A); to obtain the azide R.sub.FN.sub.3, and then performing a cycloaddition reaction of the azide R.sub.FN.sub.3 with alkyne of formula 2 ##STR00008## in the presence of copper(I) catalyst at a temperature in the range from 30 C. to the boiling point of the reaction mixture.

3. A method for preparation of compounds of general formula 3 ##STR00009## wherein R.sub.F is selected from the group consisting of C.sub.nF.sub.2n+1, C.sub.nF.sub.xH.sub.2n+1x, C.sub.nF.sub.xX.sub.2n+1x or R.sup.1CF.sub.2CF.sub.2, wherein n is an integer in the interval from 1 to 10, x is an integer in the interval from 2 to 20 and X is Cl, Br, or I, R.sup.1 is selected from the group consisting of C.sub.1-10 alkyl, ArO, ArS, imidazolyl, benzimidazolyl, or pyrazolyl and Ar is phenyl or substituted phenyl, R.sup.4 is selected from a group consisting of C.sub.1-10 alkyl, XCH.sub.2CH.sub.2, COOR.sup.3, C(CH.sub.3).sub.2OH, benzyloxy-C.sub.1-4-alkyl, pyridyl, phenyl, and pyridyl or phenyl substituted by a group selected from C.sub.1-10 alkyl, F, Cl, Br, I, OR.sup.3, NO.sub.2, NH.sub.2, CF.sub.3, wherein R.sup.3 is C.sub.1-5 alkyl, by performing the steps of: (A) generation of a synthetic equivalent of polyfluoroalkyl carbanion, said synthetic equivalent having the formula [R.sub.F].sup., by a method selected from: a) activation of trialkyl(polyfluoroalkyl)silane of general formula R.sup.3.sub.3SiR.sub.F, wherein R.sup.3 is C.sub.1-5 alkyl, with a Lewis base which is selected from the group consisting of potassium fluoride, cesium fluoride, tetramethylammonium fluoride, tetrabutylammonium fluoride, sodium carbonate, potassium carbonate, potassium phosphate, sodium acetate, potassium acetate, tetrabutylammonium acetate; b) reaction of polyfluoroalkane of general formula R.sub.FH with a base which is selected from a group consisting of methyllithium, butyllithium, phenyllithium, Grignard reagent of general formula R.sup.3MgX, wherein R.sup.3 is C.sub.1-5 alkyl, and complexes of these compounds with LiCl; or c) reaction of halopolyfluoroalkane of general formula R.sub.FBr or R.sub.FI with metalation reagents, which are selected from a group consisting of methyllithium, butyllithium, Grignard reagent of general formula R.sup.3MgX, wherein R.sup.3 is C.sub.1-5 alkyl, and complexes of these compounds with LiCl, at a temperature in the range from 78 C., or from the melting point of the reaction mixture, to +60 C., and (B) reaction of an electrophilic azidation reagent of general formula R.sup.2N.sub.3, wherein R.sup.2 is selected from the group consisting of n-C.sub.4F.sub.9SO.sub.2, ArSO.sub.2, Br, and I, wherein Ar is phenyl or substituted phenyl, with the synthetic equivalent of polyfluoroalkyl carbanion of general formula [R.sub.F].sup. generated in step (A); to obtain the azide R.sub.FN.sub.3, and then performing a cycloaddition reaction of R.sub.FN.sub.3 with alkyne of general formula 4 ##STR00010## and with iodine in the presence of tertiary amine as a base, at a temperature in the range from 30 C. to the boiling point of the reaction mixture.

4. The method according to claim 3, wherein the tertiary amine is selected from trimethylamine, N,N-diisopropylethylamine, N,N,N,N-tetramethylethylenediamine, tris((1-benzyl-1H-1,2,3-triazolyl)methyl)amine or tris((1-tert-butyl-1H-1,2,3-triazolyl)methyl)amine.

Description

EXAMPLES

List of Abbreviations

(1) Ac acetyl

(2) br.s. broad signal

(3) d doublet

(4) DMF dimethylformamide

(5) EI electron impact ionization

(6) ESI electrospray ionization

(7) Et ethyl

(8) HRMS high resolution mass spectroscopy

(9) IR infrared spectroscopy

(10) m multiplet

(11) [M].sup.+ molecular ion

(12) m.p. melting point

(13) Nf nonaflyl, nonafluorobutansulfonyl

(14) NMR nuclear magnetic resonance

(15) q quartet

(16) rt room temperature

(17) R.sub.f retention factor

(18) s singlet

(19) t triplet

(20) THF tetrahydrofuran

(21) TMS trimethylsilyl

(22) Tos p-toluenesulfonyl

(23) The subject-matter of the present invention is further illustrated by the following examples, which should not be construed as not limiting the scope of the invention.

Example 1: Azidotrifluoromethane

(24) In a two-neck round-bottom flask, CsF (3.65 g, 24 mmol) was dried under high vacuum overnight at 120 C. The flask was then cooled to rt and filled with argon. Dry DMF (44 mL) was added, the reaction mixture was stirred and cooled to 60 C. A cold solution of CF.sub.3TMS (3.55 mL, 24 mmol) and TosN.sub.3 (3.07 mL, 20 mmol) in dry DMF (6 mL) was added dropwise over 20 min and then the solution was stirred at 60 C. to 30 C. over 4 h. Cold, dry THF (40 mL) was added and the product was distilled from the reaction mixture (bath temperature max. 120 C., normal pressure) to a flask cooled to 78 C. containing PhCF.sub.3 as an internal standard. The product was obtained as a solution in THF containing TMSF as a side-product and traces of CF.sub.3H. Yield 70-80% based on .sup.19F NMR. .sup.13C NMR (101 MHz, CDCl.sub.3) =122.0 (q, .sup.1J.sub.CF=267.6 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3) =56.3 (s); HRMS (EI) m/z calculated for CF.sub.3N.sub.3 [M].sup.+: 111.0044, found 111.0040.

Example 2: Azidoperfluoroethane

(25) To a Schlenk flask filled with argon, dry THF (40 mL) was added. C.sub.2F.sub.5H (1.71 g, 14.3 mmol) was introduced, the resulting solution was cooled to 78 C. and then a solution of n-BuLi (1.6 mol.Math.l.sup.1, 8.9 mL, 14.3 mmol) in hexanes was added dropwise. The mixture was stirred at 78 C. for 30 min, the color changed from colorless to bright yellow. A solution of TosN.sub.3 (2.2 mL, 14.3 mmol) in dry THF (9.5 mL) was added dropwise and a pink precipitate formed. The mixture was stirred for another 30 min at 78 C. and then the product was distilled together with THF at temperature up to 33 C. and pressure 120 torr to a flask cooled to 78 C. containing PhCF.sub.3 as an internal standard. The product was obtained as a solution in THF. Yield 83% based on .sup.19F NMR. .sup.13C NMR (101 MHz, CDCl.sub.3) =117.0 (qt, .sup.1J.sub.CF=267.6 Hz, .sup.2J.sub.CF=41.9 Hz, CF.sub.3), 113.2 (tq, .sup.1J.sub.CF=272.9 Hz, .sup.2J.sub.CF=41.4 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =85.9 (s, 3F), 93.6 (s, 2F); HRMS (EI) m/z calculated for C.sub.2F.sub.5N.sub.3 [M].sup.+: 161.0012, found 161.0010.

Example 3: 1-Azido-1,1,2,2,3,3,3-heptafluoropropane

(26) In a screw-cap vial, CsF (0.25 g, 1.66 mmol) was dried under high vacuum at 135 C. for 48 h. The vial was then cooled to ambient temperature and filled with argon. Dry DMF (1.0 mL) was added and the mixture was cooled to 60 C. A cold solution of n-C.sub.3F.sub.7TMS (0.284 mL, 1.4 mmol) and NfN.sub.3 (0.455 g, 1.4 mmol) in dry DMF (0.5 mL) was added over 10 min and then the mixture was stirred at 60 C. to 30 C. for 4 h. Cold and dry THF (2.0 mL) was added and the product was distilled from the reaction mixture (bath temperature max. 95 C.) to a flask cooled to 78 C. containing PhCF.sub.3 as an internal standard. The product was obtained as a THF solution containing TMSF as a side-product. Yield 49-52% according to .sup.19F NMR. .sup.13C NMR (101 MHz, CDCl.sub.3) =117.1 (qt, .sup.1J.sub.CF=287.0 Hz, .sup.2J.sub.CF=33.3 Hz, CF.sub.3); 114.6 (tt, .sup.1J.sub.CF=275.7 Hz, .sup.2J.sub.CF=30.3 Hz, CF.sub.2); 107.5 (tqt, .sup.1J.sub.CF=267.7 Hz, .sup.2J.sub.CF=39.4 Hz, .sup.3J.sub.CF=11.1 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =80.9 (s, 3F), 89.1 (s, 2F), 128.3 (s, 2F); HRMS (EI) m/z calculated for C.sub.3F.sub.6N.sub.3 [MF].sup.+: 191.9994, found 191.9996.

Example 4: 1-Azido-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane

(27) In a screw-cap vial, CsF (0.25 g, 1.66 mmol) was dried under high vacuum at 135 C. for 48 h.

(28) The vial was then cooled to ambient temperature and filled with argon. Dry DMF (1.0 mL) was added and the mixture was cooled to 60 C. A cold solution of n-C.sub.8F.sub.17TMS (0.474 mL, 1.4 mmol) in dry DMF (0.5 mL) was added dropwise over 10 min and the reaction mixture was degased (one freeze-thaw cycle). A solution of NfN.sub.3 (0.455 g, 1.4 mmol) in dry DMF (0.5 mL) was added dropwise and the mixture was stirred from 60 C. to 30 C. for 4 h. Dry cold THF (2.0 mL) was added and the product was distilled from the reaction mixture together with THF (bath max. 90 C.) to a flask cooled to 78 C. containing PhCF.sub.3 as an internal standard. The product was obtained as a solid, which at temperature lower than 60 C. separated from THF. Yield 50-60% according to .sup.19F NMR. .sup.13C NMR (101 MHz, CDCl.sub.3) =117.1 (qt, .sup.1J.sub.CF=311.1 Hz, .sup.2J.sub.CF=32.3 Hz, CF.sub.3); 115.9 (tt, .sup.1J.sub.CF=292.9 Hz, .sup.2J.sub.CF=33.3 Hz, CF.sub.2 (1)); 113.5-105.1 (m, CF.sub.2 (2-7)); .sup.19F NMR (376 MHz, CDCl.sub.3) =81.3 (s, 3F), 88.6 (s, 2F), 121.6 (s, 2F), 122.4 (s, 2F), 123.2 (s, 2F), 124.4 (s, 2F), 126.3 (s, 2F), 126.6 (s, 2F). HRMS (EI) m/z calculated for C.sub.8F.sub.16N.sub.3 [MF].sup.+: 441.9837, found 441.9836.

Example 5: (2-Azido-1,1,2,2-tetrafluoroethyl)(phenyl)sulfane

(29) i-PrMgCl.LiCl (1.3 mol.Math.l.sup.1, 0.52 mL, 0.675 mmol) was added dropwise to a solution of (2-bromo-1,1,2,2-tetrafluoroethyl)(phenyl)sulfane (150 mg, 0.52 mmol) in dry THF (2 mL) at 78 C. The mixture was stirred for 5 min under argon and then a solution of NfN.sub.3 (0.337 g, 1.038 mmol) in THF (1 mL) was added. The reaction mixture was stirred at 78 C. for 20 min and then at rt for 18 h. A saturated aqueous solution of NH.sub.4Cl (6 mL) was added, the product was extracted to Et.sub.2O (310 mL), the combined organic phase was dried with MgSO.sub.4 and evaporated under reduced pressure. Purification on column chromatography (silicagel) gave product as a colorless oil. Yield 53%; IR (CHCl.sub.3, film) =2155, 1583, 1578, 1476, 1443, 1299, 1240, 1183, 1115, 1099, 1088, 1025, 892, 750, 690 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =7.72-7.63 (m, 2H), 7.56-7.48 (m, 1H), 7.48-7.42 (m, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =137.2, 130.9, 129.4, 123.3 (t, J.sub.CF=2.6 Hz), 122.5 (tt, .sup.1J.sub.CF=290.5 Hz, .sup.2J.sub.CF=39.1 Hz, CF.sub.2), 116.4 (tt, .sup.1J.sub.CF=274.3 Hz, .sup.2J.sub.CF=34.2 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =89.7 (t, .sup.2J.sub.FF=7.4 Hz, 2F), 89.8 (t, .sup.2J.sub.FF=7.4 Hz, 2F).

Example 6: 1-(2-Azido-1,1,2,2-tetrafluoroethoxy)-4-bromobenzene

(30) i-PrMgCl.LiCl (1.3 mol.Math.l.sup.1, 0.46 mL, 0.60 mmol) was added dropwise to the solution of 1-bromo-4-(2-bromo-1,1,2,2-tetrafluoroethoxy)benzene (200 mg, 0.57 mmol) in dry THF (2 mL) at 78 C. The mixture was stirred for 5 min under argon and then a solution of NfN.sub.3 (0.370 g, 1.14 mmol) in THF (1 mL) was added dropwise. The reaction mixture was stirred at 78 C. to 25 C. for 3 h. Saturated aqueous NH.sub.4Cl (6 mL) was added, the product was extracted into Et.sub.2O (310 mL), the combined organic phase was dried MgSO.sub.4 and solvent removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a colorless oil. Yield 71%; R.sub.f (hexane)=0.85; IR (CHCl.sub.3, film) =2962, 2928, 2158, 1484, 1356, 1296, 1192, 1165, 1110, 1069, 1027, 956, 825, 781 cm.sup.1; .sup.1H NMR (300.13 MHz, CDCl.sub.3) =7.11 (m, 2H), 7.52 (m, 2H); .sup.13C NMR (75.48 MHz, CDCl.sub.3) =114.2 (tt, .sup.1J.sub.CF=272 Hz, .sup.2J.sub.CF=40.0 Hz, CF.sub.2), 116.0 (tt, .sup.1J.sub.CF=276 Hz, .sup.2J.sub.CF=38.5 Hz, CF.sub.2), 120.2, 123.4 (t, .sup.4J.sub.CF=0.9 Hz), 132.9, 147.7 (t, .sup.3J.sub.CF=1.7 Hz); .sup.19F NMR (282.38 MHz, CDCl.sub.3) =94.0 (t, .sup.3J.sub.FF=2.7 Hz, 2F), 87.4 (t, .sup.3J.sub.FF=2.7 Hz, 2F).

Example 7: 1-(Pentafluoroethyl)-4-phenyl-1H-1,2,3-triazole

(31) To a 10 mL screw cap vial, phenylacetylene (0.5 mmol) and a solution of azidopentafluoroethane in THF (0.60 mmol, 3-4 mL) were added. An aqueous solution of CuSO.sub.4.5H.sub.2O (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) and sodium L-ascorbate (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) were added, the vial was closed and the content was stirred at rt for 18 h. Saturated aqueous NH.sub.4Cl (10 mL) was added and the product was extracted into CH.sub.2Cl.sub.2 (310 mL). The combined organic phase was washed with water (210 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave pure product as a white solid. Yield 84%; m.p. 82-83 C.; R.sub.f (cyklohexane:EtOAc 97:3)=0.28; IR (CHCl.sub.3, film) =1216, 1172, 1120, 1075, 691 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.13 (s, 1H), 7.90-7.86 (m, 2H), 7.51-7.46 (m, 2H), 7.45-7.40 (m, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) =148.9, 129.5, 129.2, 128.6, 126.3, 117.9, 117.2 (qt, .sup.1J.sub.CF=287.6 Hz, .sup.2J.sub.CF=41.3 Hz, CF.sub.3), 110.4 (tq, .sup.1J.sub.CF=270.9 Hz, .sup.2J.sub.CF=43.1 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =84.4 (s, 3F), 99.2 (s, 2F); HRMS (ESI) m/z calculated for C.sub.10H.sub.7N.sub.3F.sub.5 [M+H].sup.+: 264.0555, found 264.0555.

Example 8: 4-(4-Methoxyphenyl)-1-(pentafluoroethyl)-1H-1,2,3-triazole

(32) To a 10 mL screw cap vial, 4-methoxyphenylacetylene (0.5 mmol) and a solution of azidopentafluoroethane in THF (0.60 mmol, 3-4 mL) were added. An aqueous solution of CuSO.sub.4.5H.sub.2O (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) and sodium L-ascorbate (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) were added, the vial was closed and the content was stirred at rt for 18 h. Saturated aqueous NH.sub.4Cl (10 mL) was added and the product was extracted into CH.sub.2Cl.sub.2 (310 mL).

(33) The combined organic phase was washed with water (210 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave pure product as a white solid. Yield 63%; m.p. 100-102 C.; R.sub.f (cyklohexane:EtOAc, 95:5)=0.26; IR (CHCl.sub.3, film) =1618, 1501, 1434, 1223, 1123, 536 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.04 (s, 1H), 7.82-7.78 (m, 2H), 7.01-6.97 (m, 2H), 3.86 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =160.6, 148.7, 127.7, 121.2, 117.2 (qt, .sup.1J.sub.CF=287.5 Hz, .sup.2J.sub.CF=41.4 Hz, CF.sub.3), 116.9, 114.6, 110.3 (tq, .sup.1J.sub.CF=270.6 Hz, .sup.2J.sub.CF=43.1 Hz, CF.sub.2), 55.5; .sup.19F NMR (376 MHz, CDCl.sub.3) =84.4 (s, 3F), 99.2 (s, 2F); HRMS (ESI) m/z calculated for C.sub.11H.sub.9ON.sub.3F.sub.5 [M+H].sup.+: 294.0660, found 294.0661.

Example 9: 4-(2-Bromophenyl)-1-(pentafluoroethyl)-1H-1,2,3-triazole

(34) To a 10 mL screw cap vial, 2-bromophenylacetylene (0.5 mmol) and a solution of azidopentafluoroethane in THF (0.60 mmol, 3-4 mL) were added. An aqueous solution of CuSO.sub.4.5H.sub.2O (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) and sodium L-ascorbate (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) were added, the vial was closed and the content was stirred at rt for 18 h. Saturated aqueous NH.sub.4Cl (10 mL) was added and the product was extracted into CH.sub.2Cl.sub.2 (310 mL). The combined organic phase was washed with water (210 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave pure product as a white solid. Yield 37%; R.sub.f (cyklohexane:EtOAc 95:5)=0.53; IR (CHCl.sub.3, film) =1430, 1210, 1128, 1077, 972 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.63 (s, 1H), 8.15 (dd, J=7.8, 1.7 Hz, 1H), 7.70 (dd, J=8.1, 1.2 Hz, 1H), 7.47 (td, J=7.6, 1.3 Hz, 1H), 7.29 (td, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) =146.4, 133.9, 131.1, 130.6, 129.4, 128.1, 121.6, 121.4, 117.2 (qt, .sup.1J.sub.CF=287.5 Hz, .sup.2J.sub.CF=41.2 Hz, CF.sub.3), 110.3 (tq, .sup.1J.sub.CF=271.4 Hz, .sup.1J.sub.CF=43.2 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =84.4 (s, 3F), 99.2 (s, 2F); HRMS (ESI) m/z calculated for C.sub.10H.sub.6N.sub.3BrF.sub.5 [M+H].sup.+: 341.9660, found 341.9661.

Example 10: 3-(1-(Pentafluorethyl)-1H-1,2,3-triazol-4-yl)pyridine

(35) To a 10 mL screw cap vial, 3-pyridylacetylene (0.5 mmol) and a solution of azidopentafluoroethane in THF (0.60 mmol, 3-4 mL) were added. An aqueous solution of CuSO.sub.4.5H.sub.2O (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) and sodium L-ascorbate (1 mol.Math.l.sup.1, 0.05 mmol, 50 l) were added, the vial was closed and the content was stirred at rt for 18 h. Saturated aqueous NH.sub.4Cl (10 mL) was added and the product was extracted into CH.sub.2Cl.sub.2 (310 mL). The combined organic phase was washed with water (210 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave pure product as a white solid. Yield 38%; m.p. 120-122 C.; R.sub.f (cyklohexane:EtOAc 1:1)=0.48; IR (CHCl.sub.3, film) =1578, 1439, 1218, 1169, 1121, 1078 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =9.09 (d, J=2.5 Hz, 1H), 8.68 (dd, J=4.9, 1.6 Hz, 1H), 8.29 (s, 1H), 8.27 (dt, J=8.0, 2.0 Hz, 1H), 7.45 (dd, J=8.0, 4.9 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) =150.5, 147.4, 145.9, 133.7, 124.9, 124.0, 118.5, 117.1 (qt, .sup.1J.sub.CF=287.5 Hz, .sup.2J.sub.CF=40.6 Hz, CF.sub.3), 110.3 (tq, .sup.1J.sub.CF=272.2 Hz, .sup.2J.sub.CF=43.1 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =84.3 (s, 3F), 99.1 (s, 2F); HRMS (ESI) m/z calculated for C.sub.9H.sub.6N.sub.4F.sub.5 [M+H+]: 265.0507, found 265.0508.

Example 11: 4-Phenyl-1-(trifluoromethyl)-1H-1,2,3-triazole

(36) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of phenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 81%; m.p. 91-92 C.; R.sub.f (cyklohexane:EtOAc, 97:3)=0.27; IR (CHCl.sub.3, film) =1430, 1205, 1006, 694 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.14 (s, 1H), 7.89-7.86 (m, 2H), 7.50-7.46 (m, 2H), 7.44-7.40 (m, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) =148.6, 129.4, 129.2, 128.6, 126.2, 117.7 (q, .sup.1J.sub.CF=267.7 Hz, CF.sub.3), 117.3; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s); HRMS (EI) m/z calculated for C.sub.9H.sub.6N.sub.3F.sub.3 [M].sup.+: 213.0514, found 213.0520.

Example 12: 4-(p-Tolyl)-1-(trifluoromethyl)-1H-1,2,3-triazole

(37) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of 4-methylphenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 79%; m.p. 99-101 C.; R.sub.f (cyklohexane:EtOAc, 97:3)=0.19; IR (CHCl.sub.3, film)=1444, 1189, 1007, 814 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.09 (s, 1H), 7.77-7.74 (m, 2H), 7.30-7.27 (m, 2H), 2.41 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =148.7, 139.5, 129.8, 126.1, 125.8, 117.7 (q, .sup.1J.sub.CF=268.1 Hz, CF.sub.3), 116.8, 21.4; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s); HRMS (ESI) m/z calculated for C.sub.10H.sub.9N.sub.3F.sub.3 [M+H]+: 228.0743, found 228.0742.

Example 13: 4-(4-Methoxyphenyl)-1-(trifluoromethyl)-1H-1,2,3-triazole

(38) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of 4-methoxyphenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 79%; m.p. 112-115 C.; R.sub.f (cyklohexane:EtOAc, 97:3)=0.12; IR (CHCl.sub.3, film)=1445, 1257, 1215, 1194, 828 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.04 (s, 1H), 7.82-7.78 (m, 2H), 7.02-6.98 (m, 2H), 3.86 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =160.5, 148.5, 127.6, 121.2, 117.8 (q, .sup.1J.sub.CF=268.0 Hz, CF.sub.3), 116.3, 114.6, 55.5 (s); .sup.19F NMR (376 MHz, CDCl.sub.3) =59.4 (s); HRMS (ESI) m/z calculated for C.sub.10H.sub.9N.sub.3OF.sub.3 [M+H].sup.+: 244.0692, found 244.0693.

Example 14: 4-(2-Bromophenyl)-1-(trifluoromethyl)-1H-1,2,3-triazole

(39) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of 2-bromophenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a yellow oil. Yield 84%; R.sub.f (cyklohexane:EtOAc, 97:3)=0.27; IR (CHCl.sub.3, film)=1420, 1206, 1191, 760 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.63 (s, 1H), 8.16-8.14 (ddd, J=7.8, 1.7, 0.4 Hz, 1H), 7.71-7.69 (ddd, J=8.1, 1.3, 0.4 Hz, 1H), 7.49-7.45 (ddd, J=7.9, 7.4, 1.3 Hz, 1H), 7.31-7.27 (ddd, J=8.1, 7.4, 1.8 Hz, 1H); .sup.13C NMR (101 MHz, CDCl.sub.3) =146.1, 133.8, 131.0, 130.5, 129.4, 128.0, 121.4, 120.6, 117.7 (q, .sup.1J.sub.CF=268.4 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3) =59.2 (s); HRMS (ESI) m/z calculated for C.sub.9H.sub.6N.sub.3F.sub.3Br [M+H].sup.+: 291.9692, found 291.9692.

Example 15: 4-(4-Nitrophenyl)-1-(trifluoromethyl)-1H-1,2,3-triazole

(40) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of 2-nitrophenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a yellow solid. Yield 82%; m.p. 166-168 C.; R.sub.f (cyklohexane:EtOAc, 97:3)=0.25; IR (CHCl.sub.3, film)=1518, 1350, 1217, 1002 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.38-8.34 (m, 2H), 8.31 (s, 1H), 8.10-8.06 (m, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =148.3, 146.4, 134.8, 127.0, 124.6, 118.9, 117.6 (q, .sup.1J.sub.CF=269.1 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s); HRMS (CI) m/z calculated for C.sub.9H.sub.6N.sub.4O.sub.2F.sub.3 [M+H].sup.+: 259.0437, found 259.0439.

Example 16: 4-(1-(Trifluoromethyl)-1H-1,2,3-triazol-4-yl)aniline

(41) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of 4-ethynylaniline (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a yellow solid. Yield 76%; m.p. 104-106 C.; R.sub.f (cyklohexane:EtOAc:Et.sub.3N, 80:19:1)=0.14; IR (CHCl.sub.3, film) =3398, 3321, 1432, 1195, 819 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =7.98 (s, 1H), 7.67-7.64 (m, 2H), 6.77-6.73 (m, 2H), 3.86 (br s, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =149.0, 147.7, 127.5, 118.7, 117.7 (q, .sup.1J.sub.CF=267.7 Hz), 115.6, 115.2; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.4 (s); HRMS (ESI) m/z calculated for C.sub.9H.sub.8N.sub.4F.sub.3 [M+H].sup.+: 229.0696, found 229.0696.

Example 17: 4-Butyl-1-(trifluoromethyl)-1H-1,2,3-triazole

(42) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of hex-1-yne (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a yellow oil. Yield 24%; R.sub.f (cyklohexane:EtOAc, 80:19:1)=0.17; IR (CHCl.sub.3, film) =2938, 1382, 1194, 974 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =7.69 (s, 1H), 2.79 (d, J=7.7 Hz, 2H), 1.70 (dt, J=15.4, 7.5 Hz, 2H), 1.41 (dq, J=14.7, 7.4 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =149.4, 118.5, 117.7 (q, .sup.1J.sub.CF=267.3 Hz), 31.1, 25.0, 22.3, 13.8; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.4 (s); HRMS (EI) m/z calculated for C.sub.7H.sub.10N.sub.3F.sub.3 [M].sup.+: 193.0827, found 193.0828.

Example 18: Ethyl 1-(trifluoromethyl)-1H-1,2,3-triazole-4-carboxylate

(43) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of ethyl propiolate (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a yellow oil. Yield 48%; R.sub.f (cyklohexane:EtOAc, 95:5)=0.12; IR (CHCl.sub.3, film) =1744, 1444, 1266, 1222 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.53 (s, 1H), 4.48 (q, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =159.3, 140.9, 125.8, 117.4 (q, .sup.1J.sub.CF=269.8 Hz), 62.2, 14.3; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s); HRMS (ESI) m/z vypoteno pro C.sub.6H.sub.7N.sub.3O.sub.2F.sub.3 [M+H].sup.+: 210.0485, nalezeno 210.0485, calculated for C.sub.6H.sub.6N.sub.3O.sub.2F.sub.3Na [M+Na].sup.+: 232.0304, found 232.0304.

Example 19: 2-(1-(Trifluoromethyl)-1H-1,2,3-triazol-4-yl)propan-2-ol

(44) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of 2-methylbut-3-yn-2-ol (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 74%; m.p. 42-43 C.; R.sub.f (cyklohexane:EtOAc, 70:30)=0.21; IR (CHCl.sub.3, film) =3401, 1435, 1191, 982 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =7.90 (s, 1H), 2.9 (s, 1H), 1.69 (s, 6H); .sup.13C NMR (101 MHz, CDCl.sub.3) =156.8, 117.9, 117.7 (q, .sup.1J.sub.CF=268.2 Hz), 68.7, 30.4; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s); HRMS (EI) m/z calculated for C.sub.6H.sub.8N.sub.3OF.sub.3Na [M+Na].sup.+: 218.0512, found 218.0511.

Example 20: (S)-4-(2-(Benzyloxy)propyl)-1-(trifluoromethyl)-1H-1,2,3-triazole

(45) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidotrifluoromethane in THF (1.5 mmol, 3-4 mL) and a solution of (S)-((pent-4-yn-2-yloxy)methyl)benzene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a pale yellow oil. Yield 90%; R.sub.f (cyklohexane:EtOAc, 95:5)=0.09; IR (CHCl.sub.3, film) =1440, 1278, 1207, 980 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =7.71 (s, 1H), 7.34-7.27 (m, 3H), 7.26-7.22 (m, 2H), 4.61 (d, J=11.6 Hz, 1H), 4.41 (d, J=11.6 Hz, 1H), 3.92-3.85 (m, 1H), 3.02 (dd, J=15.0, 4.7 Hz, 1H), 2.96 (dd, J=15.0, 7.0 Hz, 1H), 1.28 (d, J=6.1 Hz, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =145.9, 138.4, 128.5, 127.8, 120.3, 117.7 (q, .sup.1J.sub.CF=267.9 Hz), 73.6, 70.8, 32.8, 19.5; .sup.19F NMR (376 MHz, CDCl.sub.3) =59.4 (s); HRMS (ESI) m/z calculated for C.sub.13H.sub.15N.sub.30F.sub.3 [M+H]+: 286.1162, nalezeno 286.1162, calculated for [M+Na].sup.+: 308.0981, found 308.0983.

Example 21: 1-(Pentafluoroethyl)-4-(p-tolyl)-1H-1,2,3-triazole

(46) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidopentafluoroethane in THF (1.5 mmol, 3-4 mL) and a solution of p-tolylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 88%; m.p. 92-94 C.; IR (CHCl.sub.3, film) =1219, 1175, 1122, 1075, 736 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.09 (s, 1H), 7.77-7.74 (m, 2H), 7.30-7.27 (m, 2H), 2.41 (s, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =149.0, 139.6, 129.9, 126.2, 125.8, 117.5, 117.2 (qt, .sup.1J.sub.CF=287.9 Hz, .sup.2J.sub.CF=41.4 Hz, CF.sub.3), 110.3 (tq, .sup.1J.sub.CF=270.7 Hz, .sup.2J.sub.CF=41.4 Hz, CF.sub.2), 21.5; .sup.19F NMR (376 MHz, CDCl.sub.3) =84.4 (s, 3F), 99.2 (s, 2F); HRMS (EI.sup.+) m/z calculated for C.sub.11H.sub.8N.sub.3F.sub.5 [M].sup.+: 277.0638, found 277.0639.

Example 22: 4-(1-(Pentafluoroethyl)-1H-1,2,3-triazol-4-yl)aniline

(47) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidopentafluoroethane in THF (1.5 mmol, 3-4 mL) and a solution of 4-ethynylaniline (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a yellow solid. Yield 97%; m.p. 86-89 C.; IR (CHCl.sub.3, film) =1625, 1353, 1217, 1185, 1123, 1074, 755 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.00 (s, 1H), 7.70-7.68 (m, 2H), 6.79-6.77 (m, 2H), 3.92 (br s, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =149.2, 147.6, 127.6, 118.7, 117.4 (qt, .sup.1J.sub.CF=287.3 Hz, .sup.2J.sub.CF=41.5 Hz, CF.sub.3), 116.0, 115.4, 110.3 (tq, .sup.1J.sub.CF=270.1 Hz, .sup.2J.sub.CF=42.8 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =84.4 (s, 3F), 99.2 (s, 2F); HRMS (ESI) m/z calculated for C.sub.10H.sub.8N.sub.4F.sub.5 [M+H].sup.+: 279.06636, found 279.06641.

Example 23: 1-(Pentafluoroethyl)-4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole

(48) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of azidopentafluoroethane in THF (1.5 mmol, 3-4 mL) and a solution of (4-trifluoromethyl)phenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 91%; m.p. 121-124 C.; IR (CHCl.sub.3, film) =1329, 1218, 1130, 1065, 747 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.24 (s, 1H), 8.02-8.00 (m, 2H), 7.75-7.73 (m, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =147.5, 132.0, 131.5 (q, .sup.2J.sub.CF=33.3 Hz), 126.6, 126.3 (q, .sup.3J.sub.CF=3.0 Hz), 124.0 (q, .sup.1J.sub.CF=272.7 Hz, CF.sub.3), 118.8, 117.1 (qt, .sup.1J.sub.CF=287.9 Hz, .sup.2J.sub.CF=41.4 Hz, CF.sub.3), 110.3 (tq, .sup.1J.sub.CF=271.7 Hz, .sup.2J.sub.CF=43.4 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =63.3 (s, 3F), 84.4 (s, 3F), 99.2 (s, 2F); HRMS (ESI) m/z calculated for C.sub.11H.sub.8N.sub.3F.sub.8 [M].sup.+: 331.0356, found 331.0350.

Example 24: 1-(Perfluoropropyl)-4-phenyl-1H-1,2,3-triazole

(49) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of 1-azido-1,1,2,2,3,3,3-heptafluoropropane in THF (1.5 mmol, 3-4 mL) and a solution of phenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 41%; m.p. 72-74 C.; IR (CHCl.sub.3, film) =1423, 1226, 1196, 1137, 1051, 883, 694 cm.sup.1; .sup.1H NMR (500 MHz, CDCl.sub.3) =8.12 (s, 1H), 7.89-7.87 (m, 2H), 7.50-7.46 (m, 2H), 7.44-7.40 (m, 1H); .sup.13C NMR (125.7 MHz, CDCl.sub.3) =148.9, 129.6, 129.3, 128.6, 126.3, 118.1, 117.4 (qt, .sup.1J.sub.CF=295.4 Hz, .sup.2J.sub.CF=32.7 Hz, CF.sub.3); 112.0 (tt, .sup.1J.sub.CF=272.8 Hz, .sup.2J.sub.CF=32.7 Hz, CF.sub.2); 107.6 (tq, .sup.1J.sub.CF=264.0 Hz, .sup.2J.sub.CF=40.2 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =81.0 (s, 3F), 96.5 (s, 2F), 127.6 (s, 2F); HRMS (EI) m/z calculated for C.sub.11H.sub.6N.sub.3F.sub.7 [M].sup.+: 313.0450, found 313.0445.

Example 25: 1-(Perfluorooctyl)-4-phenyl-1H-1,2,3-triazole

(50) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of 1-azido-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane in THF (1.5 mmol, 3-4 mL) and a solution of phenylacetylene (1.0 mmol) in THF (0.5 mL) were added.

(51) The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 57%; m.p. 132-133 C.; IR (CHCl.sub.3, film) =1218, 1151, 749, 671 cm.sup.1; .sup.1H NMR (500 MHz, CDCl.sub.3) =8.11 (s, 1H), 7.89-7.87 (m, 2H), 7.50-7.47 (m, 2H), 7.44-7.41 (m, 1H); .sup.13C NMR (125.7 MHz, CDCl.sub.3) =148.8, 129.6, 129.3, 128.6, 126.3, 118.1, 117.2, 112.5, 110.9, 110.82, 110.79, 110.3, 109.8, 108.5; .sup.19F NMR (470.4 MHz, CDCl.sub.3) =81.2 (t, .sup.3J.sub.FF=9.9 Hz, CF.sub.3), 95.6 (t, .sup.3J.sub.FF=11.0 Hz, CF.sub.2), 121.7 to 122.9 (m, 3CF.sub.2), 123.0 to 123.3 (m, 2CF.sub.2), 126.6 (br s, CF.sub.2); HRMS (EI) m/z calculated for C.sub.16H.sub.7N.sub.3F.sub.17 [M].sup.+: 564.03630, found 564.03631.

Example 26: 1-(Perfluoropropyl)-4-(p-tolyl)-1H-1,2,3-triazole

(52) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of 1-azido-1,1,2,2,3,3,3-heptafluoropropane in THF (1.5 mmol, 3-4 mL) and a solution of p-tolylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 41%; m.p. 86-88 C.; IR (CHCl.sub.3, film) =1236, 1139, 882, 750, 671 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.08 (s, 1H), 7.78-7.76 (m, 2H), 7.29-7.27 (m, 2H), 2.41 (s, 1H); .sup.13C NMR (101.0 MHz, CDCl.sub.3) =148.9, 129.6, 139.6, 129.9, 126.2, 125.8, 117.7, 117.4 (qt, .sup.1J.sub.CF=287.9 Hz, .sup.2J.sub.CF=28.3 Hz, CF.sub.3); 112.0 (tt, .sup.1J.sub.CF=273.7 Hz, .sup.2J.sub.CF=32.3 Hz, CF.sub.2); 107.6 (tq, .sup.1J.sub.CF=269.7 Hz, .sup.2J.sub.CF=40.4 Hz, CF.sub.2), 21.5; .sup.19F NMR (376 MHz, CDCl.sub.3) =81.0 (s, 3F), 96.5 (s, 2F), 127.7 (s, 2F); HRMS (EI) m/z calculated for C.sub.12H.sub.9N.sub.3F.sub.7 [M+H].sup.+: 328.06792, found 328.06807.

Example 27: 4-(4-Methoxyphenyl)-1-(perfluorooctyl)-1H-1,2,3-triazole

(53) To a 10 mL screw cap vial, copper(I) 3-methylsalicylate (5.4 mg, 0.025 mmol), a cold (20 C.) solution of 1-azido-1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluorooctane in THF (1.5 mmol, 3-4 mL) and a solution of 4-methoxyphenylacetylene (1.0 mmol) in THF (0.5 mL) were added. The vial was closed and the content stirred at rt for 18 h. THF was removed under reduced pressure, Et.sub.2O (20 mL) was added and the organic phase was washed with aqueous NaHCO.sub.3 (5%, 210 mL), water (10 mL), aqueous LiCl (1 mol.Math.l.sup.1, 10 mL) and brine (10 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 77%; m.p. 159-160 C.; IR (CHCl.sub.3, film) =1218, 746, 670 cm.sup.1; .sup.1H NMR (500 MHz, CDCl.sub.3) =8.02 (s, 1H), 7.82-7.80 (m, 2H), 7.01-6.99 (m, 2H), 3.87 (s, 3H); .sup.13C NMR (125.7 MHz, CDCl.sub.3) =160.6, 148.7, 127.7, 121.2, 117.2, 117.1, 114.5, 112.5, 110.9, 110.82, 110.79, 110.3, 109.8, 108.5, 55.5; .sup.19F NMR (470.4 MHz, CDCl.sub.3) =81.2 (t, .sup.3J.sub.FF=9.9 Hz, CF.sub.3), 95.6 (t, .sup.3J.sub.FF=11.6 Hz, CF.sub.2), 122.0 to 122.5 (m, 3CF.sub.2), 123.0 to 123.3 (m, 2CF.sub.2), 126.6 (br s, CF.sub.2); HRMS (EI) m/z calculated for C.sub.17H.sub.90N.sub.3F.sub.7 [M+H].sup.+: 594.04687, found 594.04695.

Example 28: 1-(Trifluoromethyl)-4-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole (Two-Step One Pot Synthesis)

(54) CsF (182 mg, 1.2 mmol) was dried in a screw-cap vial overnight under high vacuum at 120 C. Then the vial was cooled to rt, filled with argon, dry DMF (4 mL) was added and the mixture was cooled to 60 C. A solution of CF.sub.3TMS (177 l, 1.2 mmol) and TosN.sub.3 (153 l, 1.0 mmol) in dry DMF (1 mL) was added dropwise and the mixture was stirred at 60 C. to 30 C. for 4 h. A solution of (4-trifluoromethyl)phenylacetylene (1.2 mmol) in dry DMF (0.5 mL) and an aqueous solution of CuSO.sub.4.5H.sub.2O (1 mol.Math.l.sup.1, 0.12 mmol, 120 l) and sodium L-ascorbate (1 mol.Math.l.sup.1, 0.12 mmol, 120 l) were added. The vial was closed and stirred at rt for 18 h. Water (5 mL) was added, the product was extracted into Et.sub.2O (35 mL), the combined organic phase was washed with water (5 mL), aqueous LiCl (1 mol.Math.l.sup.1, 25 mL), water (5 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 50%, m.p. 112-115 C., R.sub.f (cyklohexane:EtOAc 97:3)=0.18; IR (CHCl.sub.3, film) =1444, 1223, 1204, 1109, 827 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.23 (s, 1H), 8.00 (d, J=8.0 Hz, 2H), 7.73 (d, J=8.1 Hz, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =147.2, 132.1, 131.4 (q, .sup.2J.sub.CF=32.8 Hz, CCF.sub.3), 126.5, 126.3 (q, .sup.3J.sub.CF=3.7 Hz, CCCF.sub.3), 124.0 (q, .sup.1J.sub.CF=272.1 Hz, CCF.sub.3), 118.2, 117.7 (q, .sup.1J.sub.CF=268.7 Hz, NCF.sub.3); .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s, 3F, NCF.sub.3), 63.3 (s, 3F, ArCF.sub.3); HRMS (EI) m/z calculated for C.sub.10H.sub.5N.sub.3F.sub.6 [M].sup.+: 281.0388, found 281.0391.

Example 29: 4-(4-Fluorophenyl)-1-(trifluoromethyl)-1H-1,2,3-triazole (Two-Step One Pot Synthesis)

(55) CsF (182 mg, 1.2 mmol) was dried in a screw-cap vial overnight under high vacuum at 120 C. Then the vial was cooled to rt, filled with argon, dry DMF (4 mL) was added and the mixture was cooled to 60 C. A solution of CF.sub.3TMS (177 l, 1.2 mmol) and TosN.sub.3 (153 l, 1.0 mmol) in dry DMF (1 mL) was added dropwise and the mixture was stirred at 60 C. to 30 C. for 4 h. A solution of 4-fluorophenylacetylene (1.2 mmol) in dry DMF (0.5 mL) and an aqueous solution of CuSO.sub.4.5H.sub.2O (1 mol.Math.l.sup.1, 0.12 mmol, 120 l) and sodium L-ascorbate (1 mol.Math.l.sup.1, 0.12 mmol, 120 l) were added. The vial was closed and stirred at rt for 18 h. Water (5 mL) was added, the product was extracted into Et.sub.2O (35 mL), the combined organic phase was washed with water (5 mL), aqueous LiCl (1 mol.Math.l.sup.1, 25 mL), water (5 mL), dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 81%, m.p. 110-111 C., R.sub.f (cyklohexane:EtOAc 97:3)=0.13; IR (CHCl.sub.3, film) =1444, 1207, 1011, 823 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.14 (s, 1H), 7.88-7.83 (m, 2H), 7.19-7.13 (m, 2H); .sup.13C NMR (101 MHz, CDCl.sub.3) =163.4 (d, .sup.1J.sub.CF=249.3 Hz), 147.7, 128.2 (d, .sup.3J.sub.CF=8.3 Hz), 124.9 (d, .sup.4J.sub.CF=3.4 Hz), 117.7 (q, .sup.1J.sub.CF=268.4 Hz), 117.0, 116.3 (d, .sup.2J.sub.CF=15.1 Hz); .sup.19F NMR (376 MHz, CDCl.sub.3) =59.3 (s, 3F), 111.9 (ddd, J.sub.CF=13.6, 8.5, 5.5 Hz, 1F); HRMS (EI) m/z calculated for C.sub.9H.sub.5N.sub.3F.sub.4 [M].sup.+: 231.0420, found 231.0410.

Example 30: 5-Iodo-1-(pentafluoroethyl)-4-phenyl-1H-1,2,3-triazole

(56) A cooled (20 C.) mixture of 1-azidopentafluoroethane in THF (2.7 mL, 0.64 mmol), and Et.sub.3N (145 mg, 1.43 mmol) was added dropwise to a cooled mixture of copper(I) phenylacetylide (116 mg, 0.704 mmol) and iodine (164 mg, 0.64 mmol). The mixture was stirred in a closed vial at rt for 16 h. The mixture was then poured onto water (10 mL), extracted with Et.sub.2O (310 mL), the combined organic phase was dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white solid. Yield 60%, m.p. 119-120 C., .sup.1H NMR (400 MHz, CDCl.sub.3) =7.91-7.89 (m, 2H), 7.54-7.46 (m, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =152.6, 129.7, 128.9, 128.6, 128.5, 117.2 (qt, .sup.1J.sub.CF=288.8 Hz, .sup.2J.sub.CF=38.4 Hz, CF.sub.3), 112.2 (tq, .sup.1J.sub.CF=271.7 Hz, .sup.2J.sub.CF=43.4 Hz, CF.sub.2), 71.4; .sup.19F NMR (376 MHz, CDCl.sub.3) =81.4 (s, 3F), 93.4 (s, 2F); HRMS (EI) m/z calculated for C.sub.10H.sub.6N.sub.3F.sub.5I [M+H].sup.+: 389.95211, found 389.95225.

Example 31: 4-Phenyl-1-(1,1,2,2-tetrafluoro-2-(phenylthio)ethyl)-1H-1,2,3-triazole

(57) A mixture of (2-azido-1,1,2,2-tetrafluoroethyl)(phenyl)sulfane (83 mg, 0.33 mmol), phenylacetylene (33.7 mg, 0.33 mmol), CuSO.sub.4.5H.sub.2O (3 mg, 0.019 mmol), sodium L-ascorbate (6.5 mg, 0.03 mmol), tris((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)amine (8.8 mg, 0.017 mmol), DMF (3 mL) and water (0.05 mL) was stirred in a closed vial in a microwave at 60 C. for 1 h. The mixture was then poured onto water (10 mL), extracted with Et.sub.2O (310 mL), the combined organic phase was dried (MgSO.sub.4), filtered and solvent was removed under reduced pressure. Purification by column chromatography (silicagel) gave the product as a white amorphous solid. Yield 81%, IR (CHCl.sub.3, film) =3080, 3060, 1587, 1577, 1494, 1475, 1443, 1308, 1249, 1107, 1081, 1080, 1024, 965, 901, 838, 761, 691, 520 cm.sup.1; .sup.1H NMR (400 MHz, CDCl.sub.3) =8.04 (t, J=0.7 Hz, 1H), 7.88-7.82 (m, 2H), 7.66-7.60 (m, 2H), 7.49-7.42 (m, 3H), 7.42-7.35 (m, 3H); .sup.13C NMR (101 MHz, CDCl.sub.3) =148.33, 137.17, 131.07, 129.43, 129.10, 129.01, 128.89, 126.09, 122.67 (t, .sup.4J.sub.CF=2.8 Hz), 122.02 (tt, .sup.1J.sub.CF=291.6, .sup.2J.sub.CF=39.2 Hz, CF.sub.2), 118.25, 113.50 (tt, .sup.1J.sub.CF=272.3, .sup.2J.sub.CF=35.8 Hz, CF.sub.2); .sup.19F NMR (376 MHz, CDCl.sub.3) =89.61 (t, .sup.3J.sub.FF=6.3 Hz), 95.56 (t, .sup.3J.sub.FF=6.3 Hz); HRMS (EI) m/z calculated for C.sub.16H.sub.11F.sub.4N.sub.3S [M].sup.+: 353.0610, found 353.0613.

INDUSTRIAL APPLICABILITY

(58) Compounds according to the invention can be used in the production of agrochemicals and biologically active compounds in pharmaceutical industry.