Abstract
N-arylsulfonyl-1,2,3-triazoles were synthesized from 1,1-dibromo-2-arylethylenes via a one-pot reaction involving the Cs2CO3-mediated dehydrobromination process of the dibromoalkenes to produce alkynes followed by the Cu(I)-catalyzed Huisgen cycloaddition of the alkyne intermediates with tosyl azide.
Introduction
N-arylsulfonyl-1,2,3-triazoles are known as intermediates [1–7] in organic synthesis. Conventionally, the Cu-catalyzed [3+2] cycloaddition of azides and alkynes (CuAAC) is the most significant method for the synthesis of triazole-containing compounds [8–11]. However, the employment of azides bearing electron-withdrawing groups such as sulfonyl azides result in apparently different outcomes and generates in situ a reactive ketenimine intermediate by the ring-opening rearrangement of N-arylsulfonyl copper triazole species [12–14]. Thus, the efficient synthetic approach to N-arylsulfonyl-1,2,3-triazoles by CuAAC has rarely been reported [15]. Fokin and Chang have cooperatively reported a useful copper-catalyzed approach to N-arylsulfonyl-1,2,3-triazoles carried out in anhydrous chloroform at low temperature (0°C) [16]. The efficient synthesis of N-arylsulfonyl-1,2,3-triazoles under CuBr/PhSMe conditions has been developed [17]. It has also been demonstrated that the combination of Cu(OAc)2·H2O and 2-aminophenol effectively promotes the transformation of sulfonyl azides and alkynes to give the desired N-arylsulfonyl-1,2,3-triazole [15].
1,2-Dibromo-2-arylethylenes, readily available from inexpensive aryl aldehydes by the Corey and Fuchs procedure [18], are useful and versatile precursors to the volatile and malodorous alkynes in many organic transformations [19–21]. In continuation of our work in the synthesis and application of arylvinyl bromides and dibromides [22–26], we wish to report here for the first time the one-pot conversion of 1,1-dibromo-2-arylethylenes and tosyl azide into N-arylsulfonyl-1,2,3-triazoles by sequential dehydrobromination and Huisgen [3+2] cycloaddition reaction (Scheme 1) using a CuBr/PhSMe catalytic system established by Fu for the CuAAC of normal alkynes [17].
Synthesis of N-arylsulfonyl-1,2,3-triazoles 2 from 1,1-dibromo-2-arylethylenes 1.
Results and discussion
1,1-Dibromo-2-phenylethylene (1a) was chosen as the model substrate. After the dehydrobromination of 1a (1 mmol) in DMSO (1 mL) in the presence of Cs2CO3 at 125°C for 12 h, the mixture was cooled to room temperature and treated with 1 m HCl to pH 7. Then the mixture was treated with water, p-toluenesulfonyl azide, CuBr and PhSMe in the same reaction vessel. Stirring at room temperature for 16 h afforded the desired product 2a. To optimize the reaction conditions, various reaction parameters, including solvent, the amount of base for the dehydrobromination process and the ratio of H2O/DMSO as the medium for cycloaddition, were examined. Initially, our attention was focused to find a suitable solvent for dehydrobromination that would be compatible with the aqueous conditions of the cycloaddition reaction. Among the screened solvents, DMSO proved to be the best. The reactions in 1,4-dioxane or DMF provided inferior yields. It is noteworthy that the formation of product 2a was highly sensitive to the amount of H2O present in the mixture. The optimized conditions are given in Experimental. All the products 2a–i were obtained in yields ranging from the lowest of 81% for 2h to the highest of 91% for 2b.
Conclusion
A facile synthesis of N-arylsulfonyl-1,2,3-triazoles involves dehydrobromination of readily available 1,1-dibromo-2-arylethylenes in the presence of Cs2CO3 followed by a tandem Cu(I)-catalyzed Huisgen cycloaddition reaction of the resultant alkynes with tosyl azide.
Experimental
Melting points were determined using a WRS-1B digital melting point apparatus and were uncorrected. IR spectra were recorded in KBr pellets on a Nexus FT-IR spectrophotometer. 1H NMR spectra (400 MHz) and 13C NMR spectra (100 MHz) were recorded using a Bruker DPX-400 spectrometer in CDCl3 with SiMe4 as an internal standard. Elemental analyses were performed with a Perkin-Elmer 2400 CHNS elemental analyzer. Commercially obtained reagents were used without further purification. 1,1-Dibromo-2-arylethylenes were prepared according to the reported methods [18].
General procedure for the synthesis of N-arylsulfonyl-1,2,3-triazoles 2a–i
To a stirred solution of 1,1-dibromo-2-arylethylene 1a–i (1 mmol) in DMSO (1 mL) was added Cs2CO3 (684 mg, 2.1 mmol). After stirring the mixture for 12 h at 125°C, it was cooled to room temperature and treated with 1 m HCl to reach pH 7. The resultant crude arylacetylene, without isolation, was treated with H2O (4 mL), p-toluenesulfonyl azide (237 mg, 1.2 mmol), CuBr (15 mg, 10 mol%) and PhSMe (25 mg, 20 mol%). The mixture was stirred at room temperature for 16 h. After the completion of the reaction as monitored by TLC, the mixture was diluted with ethyl acetate (20 mL) and filtered. The organic solution was washed with brine (2×20 mL) and water (20 mL), dried over Na2SO4, and then concentrated under reduced pressure. Purification of the residue by column chromatography on silica gel eluting with ethyl acetate/petroleum ether (1:5) afforded products 2a–i.
4-Phenyl-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2a)
White solid; yield 89%; mp 107.2–108.5°C (lit. [15] mp 104–105°C, lit. [16] mp [16] 107–108°C, lit. [17] mp 108–109°C); IR: 3142, 1595, 1388, 1198, 1171 cm-1; 1H NMR: δ 2.45 (3H, s), 7.37–7.45 (5H, m), 7.83 (2H, d, J = 8.8 Hz), 8.03 (2H, d, J = 8.4 Hz), 8.31 (1H, s); 13C NMR: δ 21.8, 119.0, 126.1 (2C), 128.7 (2C), 128.9, 129.0 (2C), 129.1 (2C), 130.5 (2C), 133.1, 147.4.
4-p-Tolyl-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2b)
White solid; yield 91%; mp 156–158°C (lit. [16, 17] mp 158–159°C); IR: 3101, 1592, 1394, 1196, 1180 cm-1; 1H NMR: δ 2.39 (3H, s), 2.46 (3H, s), 7.25 (2H, d, J = 8.0 Hz), 7.41 (2H, d, J = 8.0 Hz), 7.73 (2H, d, J = 8.0 Hz), 8.04 (2H, d, J = 8.0 Hz), 8.29 (1H, s); 13C NMR: δ 21.4, 21.9, 118.7, 125.6, 125.8 (2C), 128.5 (2C), 129.9 (2C), 130.4 (2C), 132.7, 139.2, 147.5, 147.5.
4-(4-Methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2c)
White solid; yield 90%; mp 112–113°C; IR: 3112, 1619, 1496, 1393, 1178 cm-1; 1H NMR: δ 2.45 (3H, s), 3.84 (3H, s), 6.95 (2H, d, J = 8.8 Hz), 7.38 (2H, d, J = 8.0 Hz), 7.75 (2H, d, J = 9.2 Hz), 8.01 (2H, d, J = 8.8 Hz), 8.22 (1H, s); 13C NMR: δ 21.8, 55.4, 114.4 (2C), 118.0, 121.5, 127.5 (2C), 128.7 (2C), 130.4 (2C), 133.2, 147.3, 147.3, 160.3. Anal. Calcd for C16H15N3O3S: C, 58.34; H, 4.59; N, 12.76. Found: C, 58.56; H, 4.56; N, 12.63.
4-(3-Methoxyphenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2d)
White solid; yield 86%; mp 90–92°C; IR: 3135, 1594, 1483, 1397, 1199, 1182 cm-1; 1H NMR: δ 2.44 (3H, s), 3.84 (3H, s), 6.92 (1H, m), 7.34–7.41 (5H, m), 8.02 (2H, d, J = 8.4 Hz), 8.31 (1H, s); 13C NMR: δ 21.8, 55.4, 111.2, 115.1, 118.5, 119.2, 128.7 (2C), 130.1, 130.1, 130.5 (2C), 133.1, 147.3, 147.4, 160.1. Anal. Calcd for C16H15N3O3S: C, 58.34; H, 4.59; N, 12.76. Found: C, 58.51; H, 4.47; N, 12.60.
4-(4-Bromophenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2e)
White solid; yield 85%; mp 156–157.5°C (lit.[16] mp 159–160°C, lit. [17] mp 157–158°C); IR: 3093, 1592, 1481, 1396, 1111 cm-1; 1H NMR: δ 2.38 (3H, s), 7.33 (2H, d, J = 8.4 Hz), 7.49 (2H, d, J = 8.4 Hz), 7.63 (2H, d, J = 8.4 Hz), 7.96 (2H, d, J = 8.4 Hz), 8.24 (1H, s); 13C NMR: δ 20.8, 118.0, 122.1, 126.6 (2C), 126.8, 127.7 (2C), 129.5 (2C), 131.2 (2C), 131.9, 145.3, 146.5.
4-(4-Chlorophenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2f)
White solid; yield 86%; mp 156–158°C. IR: 3090, 1592, 1484, 1393, 1197, 1175 cm-1; 1H NMR: δ 2.37 (3H, s), 7.31 (2H, d, J = 8.8 Hz), 7.32 (2H, d, J = 8.4 Hz), 7.68 (2H, d, J = 8.8 Hz), 7.96 (2H, d, J = 8.4 Hz), 8.24 (1H, s); 13C NMR: δ 21.9, 119.0, 127.3 (2C), 127.4, 128.8 (2C), 129.3 (2C), 130.5 (2C), 133.0, 135.0, 146.3, 147.5. Anal. Calcd for C15H12ClN3O2S: C, 53.97; H, 3.62; N, 12.59. Found: C, 54.18; H, 3.58; N, 12.45.
4-(4-Fluorophenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2g)
White solid; yield 83%; mp 124–126°C. IR: 3135, 1610, 1595, 1497, 1392, 1175 cm-1; 1H NMR: δ 2.44 (3H, s), 7.13 (2H, t, J = 8.8 Hz), 7.39 (2H, d, J = 8.4 Hz), 7.81 (2H, dd, J1 = 8.8 Hz, J2 = 5.2 Hz), 8.02 (2H, d, J = 8.4 Hz), 8.29 (1H, s); 13C NMR: δ 21.8, 116.1 (2C, d, J = 21.8 Hz), 118.7, 125.2 (2C, d, J = 3.2 Hz), 128.0 (2C, d, J = 8.4 Hz), 128.7 (2C), 130.5 (2C), 133.0, 146.5, 147.5, 163.2 (2C, d, J = 247.3 Hz). Anal. Calcd for C15H12FN3O2S: C, 56.77; H, 3.81; N, 13.24. Found: C, 56.92; H, 3.76; N, 13.14.
4-(2-Bromophenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2h)
White solid; yield 81%; mp 130–132°C; IR: 3177, 1593, 1394, 1196, 1168 cm-1; 1H NMR: δ 2.45 (3H, s), 7.21–7.67 (6H, m), 8.04 (2H, d, J = 8.4 Hz), 8.79 (1H, s); 13C NMR: δ 21.9, 121.4, 122.3, 127.8, 128.8 (2C), 129.7, 130.2, 130.5 (2C), 130.8, 133.1, 133.7, 144.9, 147.5. Anal. Calcd for C15H12BrN3O2S: C, 47.63; H, 3.20; N, 11.11. Found: C, 47.49; H, 3.26; N, 11.04.
4-(2-Chlorophenyl)-1-(toluene-4-sulfonyl)-1H-[1,2,3]triazole (2i)
White solid; yield 83%; mp 119–121°C. IR: 3188, 1591, 1469, 1395, 1198, 1179 cm-1; 1H NMR: 2.45 (3H, s), 7.30–7.47 (5H, m), 8.04 (2H, d, J = 8.4 Hz), 8.20 (1H, dd, J = 8.0 Hz, J = 2.0 Hz), 8.75 (1H, s); 13C NMR: δ 21.9, 122.4, 127.3, 127.7, 128.8 (2C), 129.9, 130.0, 130.9, 130.5 (2C), 131.9, 133.1, 143.5, 147.4. Anal. Calcd for C15H12ClN3O2S: C, 53.97; H, 3.62; N, 12.59. Found: C, 53.76; H, 3.57; N, 12.70.
Funding source: Natural Science Foundation of Henan Province
Award Identifier / Grant number: 162300410270
Funding statement: This work was supported by Natural Science Foundation of Henan province (no. 162300410270).
Acknowledgments:
This work was supported by Natural Science Foundation of Henan province (no. 162300410270).
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