An efficient method for the synthesis of 1,4-disubstituted triazoles in water at room temperature
has been developed using CuCl2 /Zn as a catalyst system. Under the optimized conditions, a novel
series of 1,4-disubstituted 1,2,3-triazoles were synthesized.
c 2012 Verlag der Zeitschrift für Naturforschung, Tübingen · http://znaturforsch.com
Table 1. Screening of solvents for the model reaction using Table 2. Screening of catalysts for the model reaction in wa-
CuSO4 (10 mol-%)/Fe powder (10 mol-%) as the catalyst ter for 60 min.a
system.a
Entry Catalyst system (10 mol-%) Time (min) Yield (%)b
Entry Solvent Time (min) Yield(%)b 1 CuSO4 /Fe 60 42
1 H2 O 150 82 2 CuSO4 /Zn 60 75
2 H2 O/DMF 150 21 3 CuCl2 /Fe 60 29
3 H2 O/DMSO 150 60 4 CuCl2 /Zn 60 90
4 H2 O/t-BuOH 150 10 5 Cu(OAc)2 /Fe 60 9
5 H2 O/EtOH 150 57 6 Cu(OAc)2 /Zn 60 34
6 H2 O/CHCl3 150 38 7 CuBr2 /Fe 60 17
7 H2 O/THF 150 11 8 CuBr2 /Zn 60 70
8 H2 O/CH3 CN 150 30 a
Model reaction conditions: propargyl phenyl ether (1 mmol), ben-
9 DMF 150 15 zyl azide (1 mmol), solvent 6 mL, the equal volume mixed for co-
a Model reaction conditions: propargyl phenyl ether (1 mmol), ben- solvent; b isolated yield.
zyl azide (1 mmol), solvent 6 mL, the equal volume mixed for co-
solvent; b isolated yield.
Table 3. Synthesis of 1,4-disubstituted 1,2,3-triazoles tra (HRMS) were performed on a MicrOTOF-Q II mass spec-
(Scheme 2). trometer with an ESI source (Waters, Manchester, UK). Sub-
Compd. R1 R2 R3 R4 R5 R6 n Time Yield stituted terminal alkynes were synthesized according to the
(min) (%) literature [15 – 19]. Benzyl azide [20] was also synthesized
1 H CH3 benzyl H NO2 H 1 90 83 according to previous reports.
2 H CH3 phenyl CH3 H NO2 0 80 80
3 H C3 H7 phenyl CF3 H H 0 50 90
General procedure for the synthesis of triazoles
4 H C3 H7 phenyl CH3 H NO2 0 75 87
5 NH2 H phenyl CF3 H H 0 80 84 A mixture of the organic azide (1.0 mmol), the termi-
6 H NO2 phenyl CH3 H NO2 0 75 82 nal alkyne (1.0 mmol) and CuCl2 (10 mol-%)/Zn powder
7 H Cl benzyl H NO2 H 1 85 85
8 OCH3 H phenyl CH3 H NO2 0 60 88
(10 mol-%) in water (6 mL) was vigorously stirred at r. t.
After completion of the reaction as indicated by TLC, the re-
The optimized relative quantities of reactants, cata- action mixture was diluted with saturated aq. NH4 Cl (20 mL)
lyst and solvent are: organic azide (1.0 mmol), termi- and extracted with CH2 Cl2 (3 × 10 mL). The combined or-
ganic layers were washed with brine (10 mL), dried over an-
nal alkyne (1.0 mmol), CuCl2 (10 mol-%)/Zn powder
hydrous Na2 SO4 and filtered. The solvent of the filtrate was
(10 mol-%) and water (6 mL).
removed in vacuo to give the pure product.
A series of 1,4-disubstituted 1,2,3-triazole deriva-
tives were synthesized based on the optimized condi- 1-(4-Nitrobenzyl)-4-(p-tolyl)-1,2,3-triazole (1)
tions (Scheme 2, Table 3). As shown in Table 3, reac-
tions between substituted terminal alkynes and organic M. p. 145 – 147 ◦C. – IR (KBr): ν (cm−1 ) = 3097, 3047,
2921, 2851, 1670, 1605, 1556, 1515, 1456, 1427, 1350, 820,
azides, including benzyl azide and phenyl azide gave
731. – 1 H NMR (400 MHz, CDCl3 ): δ = 8.21 (d, J = 8.0 Hz,
1,4-disubstituted 1,2,3-triazoles in good yields.
2H, Ar-H), 7.74 (s, 1H, CH-H), 7.69 (d, J = 8.0 Hz, 2H, Ar-
In summary, an efficient protocol for the synthesis H), 7.43 (d, J = 12.0 Hz, 2H, Ar-H), 7.22 (d, J = 8.0 Hz,
of a series of 1,2,3-triazole derivatives was established 2H, Ar-H), 5.68 (s, 2H, CH2 -H), 2.37 (s, 3H, CH3 -H). –
using CuCl2 (10 mol-%)/Zn powder (10 mol-%) as the 13 C NMR (100 MHz, CDCl ): δ = 148.6, 147.8, 142.0,
3
catalyst and water as the solvent. 138.3, 129.6, 128.5, 127.3, 125.6, 124.2, 119.8, 53.0, 21.3. –
MS (ESI): m/z (%) = 295 (100) [M+H]+ . – HRMS ((+)-
Experimental Section ESI):m/z = 295.1197 (calcd. 295.1195 for C16 H15 N4 O2 ,
General [M+H]+ ).
All the chemicals were obtained from Tianjin Kermel
1-(2-Methyl-5-nitrophenyl)-4-(p-tolyl)-1,2,3-triazole (2)
Chemical Reagent Co., Ltd. and were used as received. All
melting points were determined on a YUHUA X-3 melt- M. p. 102 – 103 ◦C. – IR (KBr): ν (cm−1 ) = 3135, 3117,
ing point apparatus and are uncorrected. IR spectra were 3065, 3030, 2980, 2921, 2859, 1633, 1600, 1521, 1440,
recorded on a Bio-rad FTS-40 spectrometer. 1 H and 13 C 1380, 1350, 810, 797, 739, 706. – 1 H NMR (400 MHz,
spectra were recorded on a Bruker Avance 400 MHz spec- CDCl3 ): δ = 8.30 (s, 1H, Ar-H), 8.28 (d, J= 4.0 Hz, 1H, Ar-
trometer operating at 400.13 and 100.61 MHz, respectively. H), 8.02 (s, 1H, CH-H), 7.80 (d, J = 8.0 Hz, 2H, Ar-H), 7.60
NMR spectra were recorded in CDCl3 or [D6 ]DMSO at r. t. (d, J= 8.0 Hz, 1H, Ar-H), 7.28 (d, J = 8.0 Hz, 2H, Ar-H), 2.43
(20 ± 2 ◦C). 1 H and 13 C chemical shifts are quoted in parts (s, 3H, CH3 -H), 2.41 (s, 3H, CH3 -H). – 13 C NMR (100 MHz,
per million downfield from TMS. ESI MS were recorded on a CDCl3 ): δ = 148.2, 146.4, 141.6, 138.6, 136.8, 132.6, 129.7,
Bruker Esquire 3000 instrument. High-resolution mass spec- 126.9, 125.7, 124.2, 121.1, 120.7, 21.3, 18.6. – MS (ESI):