General methods
Melting points were measured on a melt-temp apparatus (SMP10) and are uncorrected. TLC analyses were performed on silica gel-coated aluminium plates (Kieselgel, 0.25 mm, 60 F254, Merck, Germany), and spots were visualized by ultraviolet (UV) light absorption using a developing solvent system of ethyl acetate/hexane. The IR spectra were measured in a KBr matrix using a SHIMADZU FTIR-8400S spectrometer. 1H NMR spectra were recorded using an Advance Bruker NMR spectrometer at 400–600 MHz, whereas 13C NMR spectra were recorded on the same instrument at 100–150 MHz using tetramethylsilane (TMS) as the internal standard. High-resolution mass spectrometry (HRMS) was carried out using an LC–MS/MS impact II.
Synthesis and characterization of 2-(prop-2-yn-1-ylthio)-1H-benzo[d]imidazole (2)
To a solution of 2-mercaptobenzimidazole (1) (10 mmol) in ethanol (40 mL) and triethylamine (Et3N) (12 mmol) was added propargyl bromide (12 mmol) with stirring, and the solution was heated to reflux for 1 h. The excess solvent was removed under reduced pressure, and the resulting crude product was washed with water and recrystallized from ethanol to afford compound 2 in 94% yield as colourless crystals, mp: 163–164 °C (lit. 164–165 °C [50, 51]); IR (KBr) υmax/cm−1 1580 (C=C), 1615 (C=N), 2140 (C≡C), 2950 (C–H al), 3070 (C–H Ar), 3310 cm−1 (≡CH), 3390 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 3.20 (s, 1H, ≡CH), 4.16 (s, 2H, SCH2), 7.14–7.16 (m, 2H, Ar–H), 7.46–7.51 (m, 2H, Ar–H), 12.65 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δC = 20.6 (SCH2); 74.5, 80.5 (C≡C); 110.9, 118.0, 122.1, 122.6, 135.9, 144.1, 148.8 (Ar–C, C=N). HRMS (ESI): 188.0410 [M+].
Synthesis of 1,4-disubstituted mono-1,2,3-triazoles 4a–f
To a solution of compound 2 (1 mmol) in a 1:1 mixture of dimethyl sulfoxide (DMSO) and water (20 mL), CuSO4 (0.10 g) were added Na ascorbate (0.15 g) and the appropriate sulfonamide azide (3a–f, 1 mmol) with stirring. The resulting mixture was stirred at 80 °C for 6–8 h. The consumption of the starting materials was monitored using TLC. The reaction mixture was quenched with water, and the solid thus formed was collected by filtration, washed with a saturated solution of sodium chloride and recrystallized from ethanol to give the desired 1,2,3-triazoles (4a–f).
4-(4-((1H-Benzo[d]imidazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (4a). White solid; Yield: 90%; mp: 153–154 °C; IR (KBr) υmax/cm−1 1580 (C=C), 1620 (C=N), 2935 (C–H al), 3045 (C–H Ar), 3340–3385 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 2.26 (s, 6H, 2 × CH3), 4.76 (s, 2H, SCH2), 6.73 (bs, 1H, Ar–H), 7.13 (bs, 2H, Ar–H), 7.44–7.54 (m, 2H, Ar–H), 7.89–8.13 (m, 4H, Ar–H), 8.86 (bs, 1H, CH-1,2,3-triazole), 12.04 (bs, 1H, NH), 12.86 (s, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δC = 20.2 (CH3), 24.7 (SCH2), 110.8, 116.1, 117.4, 120.1, 122.3, 122.5, 123.7, 130.0, 138.9, 139.9, 140.2, 142.8, 143.3, 154.0, 164.2 (Ar–C, C=N). HRMS (ESI): 492.1296 [M+].
4-(4-((1H-Benzo[d]imidazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)-N-(pyrimidin-2-yl)benzenesulfonamide (4b). White solid; Yield: 87%; mp: 165–166 °C; IR (KBr) υmax/cm−1 1585 (C=C), 1625 (C=N), 2910 (C–H al), 3065 (C–H Ar), 3330–3395 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 4.74 (s, 2H, SCH2), 7.06–7.13 (m, 3H, Ar–H), 7.50 (bs, 2H, Ar–H), 8.11–8.16 (bs, 4H, Ar–H), 8.52 (bs, 2H, Ar–H), 8.87 (s, 1H, CH-1,2,3-triazole), 12.08 (bs, 1H, NH), 12.69 (bs, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δC = 26.3 (SCH2), 110.6, 116.1, 117.2, 120.6, 122.0, 122.4, 125.9, 129.9, 139.6, 140.1, 140.4, 142.6, 143.5, 155.2, 163.9 (Ar–C, C=N). HRMS (ESI): 464.1272 [M+].
4-(4-(((1H-Benzo[d]imidazol-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(pyridin-2-yl)benzenesulfonamide (4c). White solid; Yield: 85%; mp: 216–218 °C; IR (KBr) υmax/cm−1 1575 (C=C), 1610 (C=N), 2930 (C–H al), 3040 (C–H Ar), 3290–3365 cm−1 (N–H). 1H NMR (600 MHz, DMSO-d6) δH = 4.70 (s, 2H, SCH2), 6.84 (bs, 1H, Ar–H), 7.11–7.21 (m, 3H, Ar–H), 7.40–7.54 (m, 2H, Ar–H), 7.75 (m, 1H, J = 6 Hz, Ar–H), 7.84–7.95 (m, 2H, Ar–H), 7.95–8.10 (m, 4H, Ar–H), 8.81 (s, 1H, CH-1,2,3-triazole), 12.59 (bs, 1H, NH), 12.63 (bs, 1H, NH). 13C NMR (100 MHz, DMSO-d6) δC = 25.8 (SCH2), 110.4, 117.5, 120.3, 121.2, 121.8, 122.0, 125.6, 128.2, 134.2, 135.5, 138.5, 141.8, 144.8, 149.1, 163.5 (Ar–C, C=N). HRMS (ESI): 463.0975 [M+].
4-(4-((1H-Benzo[d]imidazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)-N-(thiazol-2-yl)benzenesulfonamide (4d). White solid; Yield: 89%; mp: 148–150 °C; IR (KBr) υmax/cm−1 1590 (C=C), 1610 (C=N), 2925 (C–H al), 3055 (C–H Ar), 3315–3380 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 4.72 (s, 2H, SCH2), 6.86–7.27 (m, 6H, Ar–H), 7.99 (bs, 4H, Ar–H), 8.86 (s, 1H, CH-1,2,3-triazole), 12.52 (bs, 2H, 2 × NH). 13C NMR (100 MHz, DMSO-d6) δC = 20.2 (SCH2), 110.8, 114.2, 116.1, 117.4, 122.3, 122.5, 123.7, 130.0, 135.4, 138.9, 139.9, 140.2, 142.8, 143.3, 154.5, 161.3 (Ar–C, C=N). HRMS (ESI): 469.0896 [M+].
4-(4-(((1H-Benzo[d]imidazol-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide (4e). White solid; Yield: 88%; mp: 204–206 °C; IR (KBr) υmax/cm−1 1570 (C=C), 1620 (C=N), 2975 (C–H al), 3080 (C–H Ar), 3300–3395 cm−1 (N–H). 1H NMR (600 MHz, DMSO-d6) δH = 2.21 (s, 3H, CH3), 2.55 (s, 3H, CH3), 4.81 (s, 2H, SCH2), 7.09–7.16 (m, 2H, Ar–H), 7.49–7.54 (m, 2H, Ar–H), 7.77–7.84 (m, 2H, Ar–H), 7.98–8.03 (m, 2H, Ar–H), 8.87 (s, 1H, CH-1,2,3-triazole), 10.85 (bs, 1H, NH), 13.36 (bs, 1H, NH). 13C NMR (150 MHz, DMSO-d6) δC = 21.0 (CH3), 23.2 CH3), 26.3 (SCH2), 111.0, 114.0, 117.5, 119.7, 120.5, 122.5, 127.0, 129.5, 135.8, 138.5, 139.7, 140.8, 143.1, 148.9, 162.5 (Ar–C, C=N). HRMS (ESI): 481.0934 [M+].
4-(4-(((1H-Benzo[d]imidazol-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)-N-(diaminomethylene)benzenesulfonamide (4f). White solid; Yield: 90%; mp: 244–246 °C;IR (KBr) υmax/cm−1 1570 (C=C), 1615 (C=N), 2980 (C–H al), 3025 (C–H Ar), 3265–3380 cm−1 (N–H). 1H NMR (600 MHz, DMSO-d6) δH = 4.73 (s, 2H, SCH2), 6.70 (bs, 4H, 2 × NH2), 7.13 (dd, 2H, J = 6, 12 Hz, Ar–H), 7.48 (bs, 2H, Ar–H), 7.92–8.01 (m, 4H, Ar–H), 8.81 (s, 1H, CH-1,2,3-triazole), 12.57 (bs, 2H, 2 × NH). 13C NMR (150 MHz, DMSO-d6) δC = 25.9 (SCH2), 120.2, 121.60, 122.0, 127.4, 135.7, 138.1, 144.3, 144.8, 148.8, 158.2 (Ar–C, C=N). HRMS (ESI): 428.0841 [M+].
Synthesis and characterization of 1-(prop-2-yn-1-yl)-2-(prop-2-yn-1-ylthio)-1H-benzo[d]imidazole (5)
A mixture of 2-mercaptobenzimidazole (1) (10 mmol), dimethylformamide (DMF) (20 mL) and potassium carbonate (22 mmol) were stirred at room temperature for 2 h. Then, propargyl bromide (24 mmol) was added, and the mixture was stirred overnight at room temperature. The consumption of the starting materials was monitored using TLC. The reaction mixture was poured into crushed ice. The product was collected by filtration, washed with water and recrystallized from ethanol to afford compound 5 in 91% yield as colourless crystals. mp: 72–73 °C (lit. 70–71 °C [53]); 1585 (C=C), 1610 (C=N), 2150 (C≡C), 2930 (C–H al), 3045 (C–H Ar), 3320 cm−1 (≡CH). 1H NMR (400 MHz, DMSO-d6) δH = 2.29 (s, 1H, ≡CH), 2.40 (s, 1H, ≡CH), 4.14 (s, 2H, SCH2), 4.93 (s, 2H, NCH2), 7.27–7.31 (m, 2H, Ar–H), 7.42–7.45 (m, 1H, Ar–H), 7.73–7.77 (m, 1H, Ar–H). 13C NMR (100 MHz, DMSO-d6) δC = 21.8 (SCH2); 33.6 (NCH2); 72.3, 73.8, 76.3, 78.5 (C≡C); 109.3, 118.9, 122.5, 122.7, 135.5, 143.4, 149.1 (Ar–C, C=N). HRMS (ESI): 226.0569 [M+].
Synthesis of 1,4-disubstituted bis-1,2,3-triazoles 6a–f
To a solution of compound 5 (1 mmol) in a 1:1 mixture of dimethyl sulfoxide (DMSO) and water (20 mL) were added CuSO4 (0.20 g), Na ascorbate (0.30 g) and sulfonamide azide (3a–f, 2 mmol) with stirring. The resulting mixture was stirred at 80 °C for 8–12 h. The consumption of the starting materials was monitored using TLC. The reaction mixture was quenched with water, and the solid thus formed was collected by filtration, washed with a saturated solution of sodium chloride and recrystallized from ethanol to give the desired 1,2,3-triazoles (6a–f).
N-(4,6-Dimethylpyrimidin-2-yl)-4-(4-((1-((1-(4-(N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl)-phenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]-imidazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (6a). White solid; Yield: 87%; mp: 176–178 °C; IR (KBr) υmax/cm−1 1595 (C=C), 1630 (C=N), 2915 (C–H al), 3070 (C–H Ar), 3310–3370 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 2.55 (s, 6H, 2 x CH3), 4.78 (s, 2H, SCH2), 5.56 (s, 2H, NCH2), 6.72 (bs, 2H, Ar–H), 7.20 (bs, 2H, Ar–H), 7.64–7.66 (m, 2H, Ar–H), 8.06–8.15 (m, 8H, Ar–H), 8.87 (s, 1H, CH-1,2,3-triazole), 8.95 (s, 1H, CH-1,2,3-triazole), 12.21 (s, 2H, NH). 13C NMR (100 MHz, DMSO-d6) δC = 27.2 (SCH2), 40.2 (NCH2), 23.0 (CH3), 110.5, 116.3, 117.5, 120.1, 122.3, 122.4, 122.5, 122.7, 130.2, 135.3, 139.0, 140.3, 142.6, 143.9, 149.4, 154.2, 156.2, 164.6 (Ar–C, C=N). HRMS (ESI): 834.2319 [M+].
N-(Pyrimidin-2-yl)-4-(4-((1-((1-(4-(N-pyrimidin-2-ylsulfamoyl)phenyl)-1H-1,2,3-triazol-4-yl)-methyl)-1H-benzo[d]imidazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (6b). White solid; Yield: 83%; mp: 199–201 °C; IR (KBr) υmax/cm−1 1580 (C=C), 1610 (C=N), 2925 (C–H al), 3040 (C–H Ar), 3320–3375 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 4.78 (s, 2H, SCH2), 5.57 (s, 2H, NCH2), 7.06 (s, 2H, Ar–H), 7.20 (bs, 2H, Ar–H), 7.63 (bs, 2H, Ar–H), 8.07–8.17 (m, 8H, Ar–H), 8.51 (bs, 4H, Ar–H), 8.88 (s, 2H, 2 × CH-1,2,3-triazole), 12.11 (s, 2H, 2 × NH). 13C NMR (100 MHz, DMSO-d6) δC = 26.6 (SCH2), 40.4 (NCH2), 109.8, 116.5, 118.0, 120.1, 122.0, 122.2, 122.6, 123.1, 129.4, 130.4, 135.6, 139.1, 140.2, 142.8, 143.4, 144.5, 149.8, 154.1, 156.6, 165.0 (Ar–C, C=N). HRMS (ESI): 778.12077 [M+].
N-(Pyridin-2-yl)-4-(4-(((1-((1-(4-(N-(pyridin-2-yl)sulfamoyl)phenyl)-1H-1,2,3-triazol-4-yl)-methyl)-1H-benzo[d]imidazol-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (6c). White solid; Yield: 82%; mp: 220–222 °C; IR (KBr) υmax/cm−1 1580 (C=C), 1630 (C=N), 2985 (C–H al), 3025 (C–H Ar), 3280–3350 cm−1 (N–H). 1H NMR (600 MHz, DMSO-d6) δH = 4.77 (s, 2H, SCH2), 5.54 (s, 2H, NCH2), 6.85 (bs, 2H, Ar–H), 7.19–7.26 (m, 4H, Ar–H), 7.61–7.64 (m, 2H, Ar–H), 7.75–7.77 (m, 2H, Ar–H), 7.88–7.92 (m, 2H, Ar–H), 7.97–8.04 (m, 8H, Ar–H), 8.84 (s, 1H, CH-1,2,3-triazole), 8.93 (s, 1H, CH-1,2,3-triazole), 12.41 (s, 2H, NH). 13C NMR (150 MHz, DMSO-d6) δC = 26.7 (SCH2), 40.4 (NCH2), 110.1, 117.9, 119.5, 120.3, 120.3, 121.8, 122.0, 122.1, 122.2, 128.2, 128.5, 135.9, 138.4, 142.9, 144.4, 150.3, 154.8, 156.4, 164.7 (Ar–C, C=N). HRMS (ESI): 776.2614 [M+].
N-(Thiazol-2-yl)-4-(4-((1-((1-(4-(N-thiazol-2-ylsulfamoyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (6d). White solid; Yield: 85%; mp: 158–160 °C; IR (KBr) υmax/cm−1 1580 (C=C), 1625 (C=N), 2945 (C–H al), 3030 (C–H Ar), 3325–3370 cm−1 (N–H). 1H NMR (400 MHz, DMSO-d6) δH = 4.78 (s, 2H, SCH2), 5.56 (s, 2H, NCH2), 6.87 (bs, 2H, Ar–H), 7.20–7.29 (m, 4H, Ar–H), 7.61–7.65 (m, 2H, Ar–H), 7.80–8.05 (m, 8H, Ar–H), 8.86 (s, 1H, CH-1,2,3-triazole), 8.95 (s, 1H, CH-1,2,3-triazole), 12.86 (s, 2H, 2 × NH). 13C NMR (100 MHz, DMSO-d6) δC = 27.2 (SCH2), 41.1 (NCH2), 109.0, 110.5, 118.3, 119.9, 120.8, 120.9, 122.3, 122.4, 122.5, 122.6, 125.1, 128.0, 128.2, 139.0, 139.1, 142.5, 142.6, 143.4, 143.9, 144.9, 150.8, 154.3, 169.5 (Ar–C, C=N). HRMS (ESI): 788.0685 [M+].
N-(3,4-Dimethylisoxazol-5-yl)-4-(4-(((1-((1-(4-(N-(3,4-dimethylisoxazol-5-yl)sulfamoyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazol-2-yl)thio)-methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (6e). White solid; Yield: 85%; mp: 238–240 °C; IR (KBr) υmax/cm−1 1580 (C=C), 1610 (C=N), 2955 (C–H al), 3045 (C–H Ar), 3315–3370 cm−1 (N–H). 1H NMR (600 MHz, DMSO-d6) δH = 2.08 (s, 6H, 2 × CH3), 2.57 (s, 3H, CH3), 4.80 (s, 2H, SCH2), 5.58 (s, 2H, NCH2), 7.21–7.23 (m, 2H, Ar–H), 7.53–7.63 (m, 4H, Ar–H), 7.95–8.14 (m, 6H, Ar–H), 8.92 (bs, 2H, 2 × CH-1,2,3-triazole), 10.75 (bs, 1H, NH), 11.17 (bs, 1H, NH). 13C NMR (150 MHz, DMSO-d6) δC = 18.5 (CH3), 21.0 (CH3), 26.7 (SCH2), 42.3 (NCH2), 109.8, 110.1, 117.9, 120.6, 121.9, 122.0, 122.7, 122.8, 128.6, 129.6, 135.9, 139.6, 142.8, 143.6, 144.2, 150.3, 155.0, 168.8 (Ar–C, C=N). HRMS (ESI): 812.1731 [M+].
N-(Diaminomethylene)-4-(4-(((1-((1-(4-(N-(diaminomethylene)sulfamoyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazol-2-yl)thio)methyl)-1H-1,2,3-triazol-1-yl)benzenesulfonamide (6f). White solid; Yield: 88%; mp: 276–278 °C; IR (KBr) υmax/cm−1 1575 (C=C), 1620 (C=N), 2950 (C–H al), 3040 (C–H Ar), 3260–3350 cm−1 (N–H). 1H NMR (600 MHz, DMSO-d6) δH = 4.79 (s, 2H, SCH2), 5.58 (s, 2H, NCH2), 6.80 (bs, 2H, 2 × NH2), 7.19–7.20 (m, 2H, Ar–H), 7.63–7.67 (m, 2H, Ar–H), 7.91–7.98 (m, 8H, Ar–H), 8.85 (s, 1H, CH-1,2,3-triazole), 8.92 (s, 1H, CH-1,2,3-triazole), 12.40 (bs, 2H, NH). 13C NMR (150 MHz, DMSO-d6) δC = 26.7 (SCH2), 40.1 (NCH2), 110.1, 111.3, 117.8, 120.1, 120.2, 122.1, 122.5, 122.8, 127.2, 128.3, 135.4, 137.9, 143.2, 144.3, 149.3, 158.0 (Ar–C, C=N). HRMS (ESI): 706.1343 [M+].