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Synthesis of 1,2,3 triazole-linked benzimidazole through a copper-catalyzed click reaction

  • Mohammad Bakherad EMAIL logo , Ali Keivanloo , Amir H. Amin and Amir Farkhondeh
Published/Copyright: November 28, 2019
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Heterocyclic Communications
From the journal Heterocyclic Communications Volume 25 Issue 1

Abstract

An efficient method has been developed for the synthesis of 1,2,3 triazole-linked benzimidazole through a copper-catalyzed click reaction in ethanol at 50°C. A broad range of aromatic azides were successfully reacted with n-propynylated benzimidazole via copper-catalyzed azide-alkyne cycloaddition reactions in the absence of a ligand. This method offers many advantages including short reaction times, low cost, and simple purification procedures.

Keywords: 1,2,3-triazole; Benzimidazole; Click reaction

Introduction

Over the past few years, there has been a substantial amount of interest in the development and pharmacological evaluation of benzimidazole [1, 2]. The benzimidazole scaffold represents a class of heterocyclic compounds with significant pharmacological properties such as antitumor [3], anti-microbial [4, 5], anti-viral [6], and anti-hypertensive [7] properties. Furthermore, triazoles are widely used in agrochemicals, pharmaceuticals, photographic materials, dyes, and corrosion inhibitors [8, 9, 10, 11, 12]. Triazoles have also been reported to possess anti-fungal, anti-helminthic, and anti-bacterial properties [13, 14, 15, 16].

The synthesis of 1,2,3-triazoles by copper-catalyzed alkyne-azide cycloaddition (CuAAC) reactions are established as noticeable “Click” chemistry reactions. Click reactions are one of the most beneficial catalytic techniques used for the synthesis of 1,2,3-triazoles because of its high reaction yield, wide substrate scope, and simple purification [17, 18]. A majority of published procedures for the CuAAC reactions favor simple copper salts like CuI, Cu(AcO)2, and CuSO4 as the catalysts [19, 20, 21, 22, 23]. Other copper(0) and copper(I) catalysts such as copper nano-size powder [24], copper nanoparticles adsorbed onto charcoal [25], and copper nanoclusters [26] have also shown good catalytic activities.

In view of the biological importance of benzimidazole and 1,2,3-triazoles; synthesis of the 1,2,3-triazole linked benzimidazole pharmacophore via efficient copper-catalyzed click reactions would produce novel molecular templates that are likely to exhibit interesting biological properties. Kulkarni et al. have reported the synthesis of 2-mercapto-benzimidazole-linked coumarinyl triazoles as anti-tubercular agents [27]. Eppakayala and co-workers have carried out the synthesis and biological evaluation of benzimidazole-linked 1,2,3-triazoles as potential anti-cancer agents [13]. Moreover, Rao et al. have described the synthesis of benzimidazole-appended triazole-linked 1,3-diconjugate of calix-[4]-arene as a ratiometric fluorescence off-on-off sensor for Cu2+ ions in an aqueous buffer solution [28].

In continuation of our interest in the synthesis of 1,2,3-triazole linked heterocyclic compounds [29, 30, 31], new derivatives of 1,2,3 triazole-linked benzimidazole have been synthesized via by Cu (OAc)2 catalyst in ethanol.

Results and discussion

The reaction of 2-(methylthio)-1H-benzo[d]imidazole (1) with propargyl bromide (2) in DMF in the presence of K2CO3, as a base, afforded 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3) in good yield (Scheme 1). The structure of this compound was confirmed by 1H NMR spectroscopy. The singlets observed at 2.75, 3.48, and 5.07 ppm are attributed to the SCH3, CH, and CH2 protons, respectively. The aromatic ring protons appeared as multiplets between 7.19 and 7.61 ppm.

Scheme 1 Synthesis of 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3) and 1-(prop-2-ynyl)-2-(prop-2-ynylthio)-1H-benzo[d] imidazole (5).
Scheme 1

Synthesis of 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3) and 1-(prop-2-ynyl)-2-(prop-2-ynylthio)-1H-benzo[d] imidazole (5).

Similarly, the reaction of 1H-benzo[d]imidazole-2(3H)-thione (4) with propargyl bromide (2) in DMF in the presence of K2CO3 afforded 1-(prop-2-ynyl)-2-(prop-2-ynylthio)-1H-benzo[d]imidazole 5 in good yield (Scheme 1).

The 1H NMR spectrum for (5) shows two singlets for the CH protons at 3.26 and 3.49 ppm, respectively, a singlet for the S-CH2 protons at 4.23 ppm, a singlet for the N-CH2 protons at 5.12 ppm, and two multiplets for the aromatic ring protons at 7.23-7.30 ppm and 7.6-7.65 ppm, respectively.

Compound 3 (1.0 mmol) and 1-azido-4-nitrobenzene (6a) (1.0 mmol) were selected as the model substrates to establish the optimum model reaction conditions. The results obtained were tabulated in Table 1 (Scheme 2). To optimize the reaction conditions, the above model reaction was carried out in the presence of Cu(OAc)2 (10 mol%), as a catalyst, and sodium ascorbate (20 mol%), and the effects of various solvents, catalysts, and reaction temperatures were studied. The reactions were performed using various solvents including H2O, EtOH, MeOH, DMF, CH3CN, 1,4-dioxane, THF, and dichloromethane (DCM) at 50°C (Table 1). As shown in Table 1, the highest reaction yield was obtained when ethanol was used as the solvent (Table 1, entry 2). The concentration of the catalytic copper salt was optimized, as shown in Table 1. Decreasing the loading of the catalyst to 5 mol% lowered the reaction yield dramatically (Table 1, entry 10). However, increasing the amount of catalyst to 20 mol% only shortened the reaction time and did not have any effect on the reaction yield (Table 1, entry 11). Furthermore, the effect of temperature on the conversion was studies. At room temperature and 10 mol% catalyst, the reaction had a low reaction yield (Table 1, entry 12). Increasing the temperature to 80°C did improve the overall reaction yield (Table 1, entry 13) from 45% to 94%.

Table 1

Effects of various solvents, catalysts, and temperatures on reaction of compound (3) with 1-azido-4-nitrobenzene (6a).a

EntryCatalyst (mol%)SolventTemp. (°C)Time (h)Yield (%)b
1Cu(OAc)2 (10)H2O50270
2Cu(OAc)2 (10)EtOH50195
3Cu(OAc)2 (10)MeOH50273
4Cu(OAc)2 (10)DMF50382
5Cu(OAc)2(10)CH3CN50357
6Cu(OAc)2 (10)1,4-dioxane50432
7Cu(OAc)2 (10)THF50543
8Cu(OAc)2 (10)CH2Cl250435
8CuSO4 (10)EtOH50174
9cCuI (10)EtOH50181
10Cu(OAc)2 (5)EtOH50150
11Cu(OAc)2 (20)EtOH500.595
12Cu(OAc)2 (10)EtOHRT545
13Cu(OAc)2 (10)EtOH80194

  1. aReaction conditions: compound (3) (1.0 mmol), 1-azido-4-nitrobenzene (6a) (1.0 mmol), copper salt, sodium ascorbate (twice the amount of copper salt), solvent (5 mL).

    bIsolated yield.

    cWithout sodium ascorbate.

Scheme 2
Scheme 2

In order to illustrate the versatility of this method, a series of aromatic azides were studied under the optimized reaction conditions, and the results obtained were tabulated in Table 2 (Scheme 3). A broad scope of different aromatic azides was tested, and 2-(methylthio)-1-((1-aryl-1H-1,2,3-triazol-4-yl) methyl)-1H-benzo[d]imidazoles (7) were obtained in good-to-excellent yields. As shown in Table 2, the steric effects of the substituents at the ortho-position of the aromatic azides did not have a clear effect on the reaction yields.

Scheme 3
Scheme 3
Table 2

Synthesis of 2-(methylthio)-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (7).a

EntryArN3ProductTime (h)Mp (°C)Yield (%)b
11162-16495
22173-17590
33142-14380
42155-15985
52183-18688

  1. aReaction conditions: compound (3) (1.0 mmol), aryl azide (6) (1.0 mmol), Cu(OAc)2 (10.0 mol%), NaAs (20 mol%), ethanol (5 mL), 50°C.

    bIsolated yield.

To extend the scope of our work, the click reaction of compound (5) with aromatic azides (6) were studied in the presence of 10 mol% of Cu(OAc)2 and 20 mol% of sodium ascorbate in ethanol at 50°C (Table 3, and Scheme 4). As shown in this table, different aryl azides reacted successfully in the developed catalytic system. The corresponding products were isolated in good-to-high yields.

Scheme 4
Scheme 4
Table 3

2-((1-aryl-1H-1,2,3-triazol-4-yl)methylthio)-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (8).a

EntryArN3ProductTime (h)Mp (°C)Yield (%)b
13181-18283
24203-20485
33193-19580

  1. aReaction conditions: compound (5) (1.0 mmol), aryl azide (6) (1.0 mmol), Cu(OAc)2 (10.0 mol%), NaAs (20 mol%), ethanol (5 mL), 50°C.

    bIsolated yield.

The copper-catalyzed click reaction mechanism comprises the multi-general steps shown in Scheme 5: a) 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3) was converted to its corresponding copper(I) acetylide intermediate (1) in the presence of Cu(OAc)2/NaAs; b) the formation of six-membered ring copper metallacycle (2) by treatment of intermediate (1) with aromatic azide (5); c) cyclization takes place to yield the copper triazole intermediate (4); d) proteolysis of the Cu-C bond gives product (6) and regenerates the catalyst.

Scheme 5 Proposed mechanism.
Scheme 5

Proposed mechanism.

Conclusion

An efficient and versitile method for the synthesis of triazole-linked bezimidazole derivatives has been developed utilising the click reaction of propynylated benzimidazole compound 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3) or 1-(prop-2-ynyl)-2-(prop-2-ynylthio) -1H-benzo[d]imidazole (5) with aromatic azides catalyzed by Cu (OAc)2. The short reaction time, mild experimental conditions, simple purification procedures and good-to-high yields are some advantages of this method.

Experimental

General

The reagents and solvents used were supplied from Merck, Fluka or Aldrich. Melting points were determined using an electro-thermal C14500 apparatus. The reaction progress and the purity of compounds were monitored using TLC analytical silica gel plates (Merck 60 F250). The 1H NMR (300 MHz) and 13C NMR (75 MHz) spectroscopies were run on a Bruker Advance DPX-250 FT-NMR spectrometer. The chemical shift values were given as δ values against tetramethylsilane (TMS) as the internal standard, and the J values were given in Hz. The microanalyses were performed on a Perkin-Elmer 240-B microanalyzer.

Synthesis of 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3)

Propargyl bromide (2) (1.2 mmol, 0.1 mL) was added slowly to a stirring mixture of 2-(methylthio)-1H-benzo[d] imidazole (1) (1.0 mmol, 0.16 g) and K2CO3 (2.0 mmol, 0.20 g) in dry DMF (3 mL) at room temperature, and the resulting mixture was stirred at room temperature for 10 h. Upon completion of the reaction, the solvent was evaporated under vacuum, and the resulting product was washed with water. The residue was purified by crystallization from EtOH to give the title compound. Yield, 90%; White powder; Mp., 202-204°C; 1H-NMR (300 MHz, DMSO-d6): δ 2.75 (s, 3H, CH3), 3.48 (s, 1H, CH), 5.07 (s, 2H, CH2), 7.19-7.23 (m, 2H, ArH), 7.56-7.61 (m, 2H, ArH); 13C-NMR (75 MHz, DMSO-d6): δ 14.9, 76.3, 78.1, 110.0, 118.1, 122.1, 122.2, 136.1, 143.3, 152.6, 162.8; Anal. Calcd. for C11H10N2S: C, 65.32; H, 4.98; N, 13.85%; Found: C, 65.13; H, 4.89; N, 13.69%.

1-(prop-2-ynyl)-2-(prop-2-ynylthio)-1H-benzo[d] imidazole (5)

To a mixture of 1H-benzo[d]imidazole-2(3H)-thione (4) (1.0 mmol, 0.15 g) and K2CO3 (3.0 mmol, 0.4 g) in dry DMF (4 mL) were added propargyl bromide (2) (2.4 mmol, 0.2 mL). The reaction mixture was stirred at room temperature until the disappearance of compound (4) (monitored by TLC). The solvent was evaporated to dryness, the crude product was washed with H2O, and the precipitate formed was purified by recrystallization from methanol. Yield, 86%; White powder; Mp., 224-226°C; 1H-NMR (300 MHz, DMSO-d6): δ 3.26 (s, 1H, CH),3.49 (s, 1H, CH), 4.23 (s, 2H, CH2), 5.12 (s, 2H, CH2), 7.23-7.30 (m, 2H, ArH), 7.60-7.65 (m, 2H, ArH); 13C-NMR (75 MHz, DMSO-d6): δ 21.0, 74.7, 76.4, 76.5, 78.1, 80.2, 81.6, 83.1, 110.4, 118.5, 122.5, 122.6, 136.0, 143.2, 149.8; Anal. Calcd. for C13H10N2S: C, 69.00; H, 4.45; N, 12.38%; Found: C, 69.18; H, 4.53; N, 12.55%.

Synthesis of 2-(methylthio)-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imida-zole (7a-e)

A round-bottomed flask was charged with 2-(methylthio)-1-(prop-2-ynyl)-1H-benzo[d]imidazole (3) (1.0 mmol, 0.2 g), an aromatic azide (6) (1.0 mmol), Cu(OAc)2 (0.1 mmol, 0.18 g), sodium ascorbate (0.2 mmol, 0.4 g), and ethanol (3.0 mL). The resulting mixture was stirred at 50°C until the disappearance of compound (3) (monitored by TLC). Upon completion of the reaction, the resulting mixture was washed with a (1:1) mixture of H2O and conc. NH3 to remove the catalyst. The residue was finally purified by flash column chromatography (hexane/ethyl acetate = 10:1) to give the desired product (Table 2).

2-(methylthio)-1-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl) methyl)-1H-benzo[d]imid- azole (7a)

1H-NMR (300 MHz, DMSO-d6 ): δ 2.76 (s, 3H, CH3), 5.55 (s, 2H, CH2), 7.18-7.22 (m, 2H, ArH), 7.56-7.58 (d, 1H, J = 6.2 Hz, ArH), 7.62-7.65 (d, 1H, J = 6.2 Hz, ArH), 8.18-8.21 (d, 2H, J = 9.3 Hz, ArH), 8.40-8.43 (d, 2H, J = 9.3 Hz, ArH), 9.06 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 14.9, 110.2, 118.0, 121.1, 122.0, 122.1, 122.7, 125.9, 141.1, 143.5, 144.2, 147.2; Anal. Calcd. for C17H14N6O2S: C, 55.73; H, 3.85; N, 22.94%; Found: C, 55.92; H, 3.94; N, 23.11%.

2-(methylthio)-1-((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl) methyl)-1H-benzo[d]imid- azole (7b)

1H-NMR (300 MHz, DMSO-d6 ): δ 2.76 (s, 3H, CH3), 5.54 (s, 2H, CH2), 7.14-7.22 (m, 2H, ArH), 7.56-7.58 (m, 2H, ArH), 7.62-7.64 (m, 2H, ArH), 7.80-7.86 (t, 1H, J = 7.3 Hz, ArH), 8.27-8.29 (d, 1H, J = 7.3 Hz, ArH), 8.35-8.38 (d, 1H, J = 7.3 Hz, ArH), 8.70 (s, 1H, ArH), 9.09 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6): δ 14.8, 110.2, 115.2, 118.0, 122.0, 122.1, 122.7, 123.5, 126.5, 131.8, 137.4, 143.5, 144.0, 148.8; Anal. Calcd. for C17H14N6O2S: C, 55.73; H, 3.85; N, 22.94%; Found: C, 55.91; H, 3.77; N, 22.79%.

1-((1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-(methylthio)-1H-benzo[d]imid- azole (7c)

1H-NMR (300 MHz, DMSO-d6 ): δ 2.79 (s, 3H, CH3), 5.57 (s, 2H, CH2), 7.21 (d, 2H, ArH), 7.56-7.63 (m, 4H, ArH), 7.90-7.92 (d, 1H, J = 6.0 Hz, ArH), 8.04 (s, 1H, ArH ), 8.96 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 15.0, 19.0, 56.5, 110.2, 117.5, 118.0, 122.1, 122.1, 122.7, 125.0, 125.2, 133.5, 136.0, 143.4, 144.2, 148.4; Anal. Calcd. for C17H14ClN5S: C, 57.38; H, 3.97; N, 19.68%; Found: C, 57.56; H, 4.07; N, 19.87%.

1-((1-(2-chloro-4-nitrophenyl)-1H-1,2,3-triazol-4-yl) methyl)-2-(methylthio)-1H-benzo-[d]imidazole (7d)

1H-NMR (300 MHz, DMSO-d6 ): δ 2.76 (s, 3H, CH3), 5.59 (s, 2H, CH2), 7.16-7.23 (m, 2H, ArH), 7.56-7.59 (d, 1H, J = 6.9 Hz, ArH), 7.65-7.68 (d, 1H, J = 6.9 Hz, ArH), 7.98-8.01 (d, 1H, J = 6.9 Hz, ArH), 8.35-8.39 (d of d, 1H, J = 2.3 Hz, J = 6.9 Hz, ArH), 8.60-8.61 (d, 1H, J = 2.3 Hz, ArH), 8.80 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 15.0, 110.3, 118.0, 122.1, 123.9, 126.2, 126.4, 129.6, 129.7, 139.4, 142.9, 143.5, 148.7; Anal. Calcd. for C17H13ClN6O2S: C, 50.94; H, 3.27; N, 20.97%; Found: C, 50.76; H, 3.19; N, 20.82%.

1-((1-(4-chloro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl) methyl)-2-(methylthio)-1H-benzo-[d]imidazole (7e)

1H-NMR (300 MHz, DMSO-d6 ): δ 2.77 (s, 3H, CH3), 5.57 (s, 2H, CH2), 7.16-7.23 (m, 2H, ArH), 7.57-7.60 (d, 1H, J = 6.3 Hz, ArH), 7. 61-7.64 (d, 1H, J = 6.3 Hz, ArH), 7.98-8.01 (d, 1H, J = 8.4 Hz, ArH), 8.26-8.29 (d of d, 1H, J = 2.1 Hz, J = 8.4 Hz, ArH), 8.67-8.68 (d, 1H, J = 2.1 Hz, ArH), 9.01 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 14.9, 110.3, 118.0, 119.1, 120.3, 122.1, 122.5, 129.0, 132.0, 134.6, 137.9, 143.8; Anal. Calcd. for C17H13ClN6O2S: C, 50.94; H, 3.27; N, 20.97%; Found: C, 50.78; H, 3.35; N, 21.13%.

2-((1-aryl-1H-1,2,3-triazol-4-yl)methylthio)-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (8a-c)

A round-bottomed flask was charged with 1-(prop-2-ynyl)-2-(prop-2-ynylthio)-1H-benzo[d]imidazole (5) (1.0 mmol, 0.22 g), an aromatic azide (6) (1.0 mmol), Cu(OAc)2 (0.1 mmol, 0.18 g), sodium ascorbate (0.2 mmol, 0.4 g), and ethanol (3.0 mL). The mixture was stirred at 50°C. After completion of the reaction, the resulting mixture was washed with a (1:1) mixture of H2O and conc. NH3 to remove the catalyst. The residue was purified by flash column chromatography (hexane/ethyl acetate = 10:1) to give the desired product (Table 3).

2-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methylthio)-1-((1-(4-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (8a)

1H-NMR (300 MHz, DMSO-d6 ): δ 4.81 (s, 2H, CH2), 5.60 (s, 2H, CH2), 7.23-7.24 (m, 2H, ArH), 7.65-7.67 (m, 2H, ArH), 8.13-8.18 (d, 4H, J = 1.6 Hz, ArH), 8.38-8.41 (d, 4H, J = 1.6 Hz, ArH), 8.96 (s, 1H, CH of triazole), 9.03 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 27.3, 31.1, 110.6, 118.4, 121.0, 121.0, 122.3, 122.5, 122.7, 122.7, 125.3, 125.9, 126.7, 136.3, 141.0, 141.1, 143.4, 144.2, 145.4, 147.1, 147.1; Anal. Calcd. for C25H18N10O4S: C, 54.15; H, 3.27; N, 25.26%; Found: C, 54.35; H, 3.38; N, 25.44%.

2-((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methylthio)-1-((1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (8b)

1H-NMR (300 MHz, DMSO-d6 ): δ 4.81 (s, 2H, CH2), 5.50 (s, 2H, CH2), 7.22-7.25 (m, 2H, ArH), 7.64-7.70 (m, 2H, ArH), 7.83-7.88 (t, 2H, J = 5.3 Hz, ArH), 8.29-8.38 (m, 4H, ArH), 8.65-8.68 (d, 2H, J = 5.3 Hz, ArH), 9.0 (s, 1H, CH of triazole), 9.09 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 27.4, 110.6, 115.2, 118.4, 122.3, 122.5, 122.7, 122.8, 123.5, 123.6, 126.5, 126.5, 131.9, 137.4, 135.7, 143.4, 144.0, 148.9; Anal. Calcd. for C25H18N10O4S: C, 54.15; H, 3.27; N, 25.26%; Found: C, 54.37; H, 3.17; N, 25.08%.

2-((1-(4-chloro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl) methylthio)-1-((1-(4-chloro-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-benzo[d]imidazole (8c)

1H-NMR (300 MHz, DMSO-d6 ): δ 4.80 (s, 2H, CH2), 5.80 (s, 2H, CH2), 7.22-7.24 (m, 2H, ArH), 7.63-7.65 (m, 2H, ArH), 7.96-7.99 (d, 2H, J = 5.3 Hz, ArH), 8.21-8.24 (d, 2H, J = 5.3 Hz, ArH), 8.63 (s, 2H, ArH), 8.92 (s, 1H, CH of triazole), 8.97 (s, 1H, CH of triazole); 13C-NMR (75 MHz, DMSO-d6 ): δ 27.3, 110.6, 117.4, 122.3, 122.5, 122.7, 122.8, 124.9, 125.0, 125.1, 125.1, 133.5, 136.0, 136.0, 143.4, 145.4, 148.4; Anal. Calcd. for C25H16Cl2N10O4S: C, 48.16; H, 2.59; N, 22.47%; Found: C, 48.34; H, 2.67; N, 22.62%.

Acknowledgment

We gratefully acknowledge the financial support of the Research Council of the Shahrood University of Technology.

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Received: 2019-01-28
Accepted: 2019-04-25
Published Online: 2019-11-28

© 2019 Mohammad Bakherad et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 Public License.

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https://doi.org/10.1515/hc-2019-0016
Keywords for this article
1,2,3-triazole; Benzimidazole; Click reaction
Creative Commons
BY 4.0

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