Introduction

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for treatment of pain and inflammation. NSAIDs act by blocking the cyclooxygenase (COX) enzyme and thus biosynthesis of prostaglandins (PGs) [1]. Cyclooxygenases (COXs) are the key enzymes in synthesis of prostaglandins, the main mediators of inflammation, pain, and increased body temperature (hyperpyrexia) [2]. NSAIDs block the COX enzymes and reduce prostaglandins throughout the body. As a consequence, ongoing inflammation, pain, and fever are reduced. However, NSAIDs have a number of adverse effects, mainly because of their inhibition of the constitutive isoform of COX. COX-1 and COX-2 are two isomeric forms of COX enzyme. Imidazoles, chalcones, and 1,2,3-triazoles are privileged heterocyclic structures present in various natural products and synthetic pharmaceuticals. Compounds containing imidazole moiety play an important role due to their biological activity. Imidazole derivatives have been found to exhibit diverse activities such as analgesic [3], antiinflammatory [4,5,6,7], antimicrobial [8,9,10], anticancer [11, 12], antitubercular [13], antiviral [14], anticonvulsant [15], and antidepressant [16] effects. Similarly, triazole derivatives occupy a unique position in heterocyclic chemistry due to their unique chemical and structural properties, receiving much attention over recent years and finding wide applications in medicinal chemistry [17]. The 1,2,3-triazole heterocyclic ring system shows significant biological activities, such as antiinflammatory [18], antibacterial [19], antiviral [20], anti-human immunodeficiency virus (HIV) [21], antidiabetic [22], DNA cleavage [23], and potassium channel activation [24] effects. On the other hand, chalcones represent an important group of natural products [25, 26]. Chalcones containing several functional groups exhibit a wide spectrum of biological activities, including antiinflammatory [27], antileishmanial [28], antimalarial [29], antitumor [30], and antibacterial [31] effects. Some known imidazole/chalcone derivatives (1–4) are shown in Fig. 1, while 1,2,3-triazole derivatives (5–7) reported as pharmacologically active agents are presented in Fig. 2.

Fig. 1
figure 1

Selected examples of imidazole/chalcone derivatives with pharmacological activity

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Fig. 2
figure 2

Selected examples of 1,2,3-triazole derivatives with pharmacological activity

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The biological potency of imidazole, 1,2,3-triazole, and chalcone pharmacophores prompted us to synthesize the title compounds, hoping that their incorporation into a single structural entity could result in novel compounds. In the present study, we synthesized a series of novel 3-phenyl-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one derivatives 6a–j and propose the molecular interactions and binding mode of these compounds with COX targets based on in silico molecular docking studies.

Results and discussion

Chemistry

We synthesized 1,2,3-triazole chalcone derivatives of 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol. All title compounds were synthesized using four different steps. In the first step, substituted 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol 1a, b was prepared by stirring a mixture of benzil, aniline, 4-hydroxybenzaldehyde/4-hydroxy-3-methoxybenzaldehyde, ammonium acetate, and 10 mol% iodine in 5 ml ethanol at 75 °C for 1 h. In the second step, 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol 1a, b was condensed with propargyl bromide in presence of K2CO3 in dimethylformamide (DMF) under reflux for 2 h to obtain corresponding propargyl products 2a, b. In the next step, chalcone azides 5a–e were synthesized by aldol condensation reaction of 1-(4-azidophenyl)ethan-1-one 3 with various substituted benzaldehydes 4a–e. In the final step, intermediate 2a, b was subjected to cycloaddition with chalcone azides 5a–e under click chemistry reaction conditions in presence of copper(I) as catalyst in dry tetrahydrofuran (THF) for 12 h to obtain novel corresponding derivatives of 3-phenyl-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one 6a–j in quantitative yields.

All title derivatives were characterized by 1H and 13C nuclear magnetic resonance (NMR), infrared (IR), and electrospray ionization (ESI) mass spectroscopy (MS) analyses. The 1H NMR signals appearing at δ 4.66 and 2.51 ppm confirm the O-propargylation of compound 2a. All the triazole chalcone derivatives 6a–j showed IR absorption bands from 3088 to 2971 cm−1, corresponding to aromatic C–H stretching. Absorptions due to C=C, C=O, and C=N stretching were also observed at 1674 to 1670, 1711 to 1705, and 1244 to 1234 cm−1, respectively. In 1H NMR spectra, presence of singlet resonances at δ 5.30 to 5.22 ppm and 9.16 to 8.51 ppm were attributed to methylene protons attached to oxygen atom and proton of 1,2,3-triazole ring, respectively, whereas corresponding carbon resonances were observed in the 13C NMR spectra at 60.94 to 60.01 and 123.3 to 122.5 ppm, respectively. All other protons and carbons resonated in expected regions.

  • Step 1 Synthesis of 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol 1a, b

    figure a

  • Step 2 Synthesis of 1,4,5-triphenyl-2-(4-(prop-2-yn-1-yloxy)phenyl)-1H-imidazole 2a, b (propargylation)

    figure b

  • Step 3 Synthesis of azidochalcones 5a–e

    figure c

  • Step 4 Synthesis of 3-phenyl-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one derivatives 6a–j

    figure d

In silico molecular docking studies with cyclooxygenase-1 and cyclooxygenase-2

The molecular interaction of the title compounds was explored through molecular docking studies using Discovery Studio 2.1 software. The compounds were evaluated for their inhibitory effect on cyclooxygenase-1 (COX-1, PDB ID 2OYE) and cyclooxygenase-2 (COX-2, PDB ID 4PH9). For this study, crystallographic data for COX-1 and COX-2 were retrieved from the Protein Data Bank (http://www.rcsb.org). Retrieved crystal structures were cleaned, and hydrogen atoms added. All heteroatoms were removed before docking study, and the docking energies (LibDock) of the title derivatives towards the antiinflammatory targets were explored. All compounds docked to the selected targets, and the docking results were compared with the standard control drugs indomethacin for COX-1 and ibuprofen for COX-2. The docking analysis of the synthesized compounds with COX-1 and COX-2 gave their docking scores and interaction patterns. All the docked compounds exhibited good docking scores in the range from 208.357 to 161.285 as compared with 145.934 for indomethacin (Table 1), and 168.763 to 147.904 as compared with 145.934 for ibuprofen (Table 2). Among all the compounds, 6b showed good docking score of 208.357 and 168.763 as well as good interactions with binding-site residues of the target proteins COX-1 and COX-2, respectively. The docking pose of all the compounds revealed significant interaction with the active site of the respective targets. Moreover, potential hydrophobic contacts were found at the active site of the receptors. The significant docking score values imply that these compounds could represent potential leads for future nonsteroidal antiinflammatory drugs (NSAIDs). The protein–ligand interaction of the compounds is visualized in Figs. 3 and 4.

Table 1 Docking score (LibDock) and ligand interaction data for compounds 6a–j with active-site residues of cyclooxygenase-1 (PDB ID 2OYE)
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Table 2 Docking score (LibDock) and ligand interaction data of compounds 6a–j with active-site residues of cyclooxygenase-2 (PDB ID 4PH9)
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Fig. 3
figure 3

Receptor–ligand hydrogen bonds (green) and bumps (pink) of compounds 6b, d, e, i, j, and indomethacin with active-site residues of cyclooxygenase-1 (PDB ID 2OYE). (Color figure online)

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Fig. 4
figure 4

Receptor–ligand hydrogen bonds (green) and bumps (pink) of compounds 6b, c, d, i, j, and ibuprofen with active-site residues of cyclooxygenase-2 (PDB ID 4PH9). (Color figure online)

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Experimental

Chemistry

Melting points of all compounds were recorded on Cassia-Siamia (VMP-AM) melting point apparatus and are uncorrected. IR spectra were recorded on a PerkinElmer FT-IR 240-C spectrometer using KBr optics. NMR spectra were recorded on Bruker Advance 400 MHz with tetramethylsilane (TMS) as internal standard; chemical shifts are expressed in δ ppm. Mass spectra were recorded on Hewlett Packard mass spectrometer operating at 70 eV. All reactions were monitored on silica gel precoated thin-layer chromatography (TLC) plates from Merck, and spots were visualized with ultraviolet (UV) light. Silica gel (100–200 mesh) used for column chromatography was procured from Merck.

Synthesis of 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol ( 1 )

Mixture of benzil (10 mmol), aniline (10 mmol), p-hydroxyaldehyde (10 mmol), ammonium acetate (10 mmol), and iodine (10 mol%) in 5 ml ethanol was stirred at 75 °C for 5 h. Reaction completion was monitored by TLC. After reaction completion, the reaction mixture was diluted with water (containing a small amount of Na2S2O3). The solid imidazole products that separated out were filtered, washed with water, and dried. The crude products thus obtained were pure and subjected to further purification by column chromatography on silica gel (60–120 mesh size) using 25% ethylacetate in hexane as eluent to yield 4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenol 1.

Synthesis of 1,4,5-triphenyl-2-(4-(prop-2-yn-1-yloxy)phenyl)-1H-imidazole derivatives 2a , b

4-(1,4,5-Triphenyl-1H-imidazol-2-yl)phenol 1 (1.0 mol) along with 1.5 mol potassium carbonate was taken in dimethylformamide (DMF), and propargyl bromide (1.5 mol) in DMF was added to this solution. The reaction mixture was stirred (reflux) to afford crude 1,4,5-triphenyl-2-(4-(prop-2-yn-1-yloxy)phenyl)-1H-imidazole. This crude residue was purified by column chromatography over silica gel (100–200 mesh) in 15% ethyl acetate in hexane to obtain compound 2 in pure state.

1,4,5-Triphenyl-2-(4-(prop-2-yn-1-yloxy)phenyl)-1H-imidazole ( 2a )

Yield 88%, m.p. 149–151 °C; 1H NMR (400 MHz, CDCl3): δ 2.51 (s, 1H, CH), 4.66 (s, 2H, O–CH2), 6.84 (d, J = 8.8 Hz, 2H, H-ph), 7.06–7.01 (m, 2H, H-ph), 7.13–7.10 (m, 2H, H-ph), 7.19 (s, 2H, H-ph), 7.28–7.21 (m, 7H, H-ph), 7.37 (d, J = 8.8 Hz, 2H, H-ph), 7.59 (d, J = 7.2 Hz, 2H, H-ph); 13C NMR (400 MHz, CDCl3): δ 55.7, 75.6, 78.3, 114.5, 124.1, 126.5, 127.3, 127.9, 128.2, 128.3, 128.5, 128.6, 129.0, 129.9, 130.2, 130.6, 130.7, 131.1, 134.6, 138.5, 146.6, 157.5; ESI–MS: m/z 427 (M + 1) observed for C30H22N2O.

Synthesis of 1-(4-azidophenyl)-3-phenylprop-2-en-1-one derivatives 5a – e

Mixture of 1-(4-azidophenyl)ethan-1-one 3 (1.0 mmol) in 10 mL EtOH, KOH (1.0 mmol), and substituted benzaldehyde 4a–e (1.0 mmol) was stirred at room temperature (RT) for 1 h. After dilution with water (100 mL), the resulting solid was filtered off, washed with water, and recrystallized from EtOH to obtain yellow compound 5a–e.

1-(4-Azidophenyl)-3-phenylprop-2-en-1-one ( 5a )

Yield 81%, m.p. 119–121 °C; 1H NMR (400 MHz, CDCl3): δ 7.18–7.10 (m, 2H, H-ph), 7.46–7.40 (m, 3H, H-ph), 7.52 (d, J = 15.7 Hz, 1H, =CH), 7.65 (d, J = 3.7 Hz, 2H, H-ph), 7.83 (d, J = 15.7 Hz, 1H, =CH), 8.06 (d, J = 8.7 Hz, 2H, H-ph).

Synthesis of 3-phenyl-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one derivatives 6a–j

Intermediate, 1,4,5-triphenyl-2-(4-(prop-2-yn-1-yloxy)phenyl)-1H-imidazole 2a, b (3.0 mmol) was dissolved in dry THF (10 mL), and catalytic amount of copper iodide was added. To this, substituted 1-(4-azidophenyl)-3-phenylprop-2-en-1-one 5a–e (3.0 mmol) in dry THF was added slowly while stirring at room temperature under nitrogen atmosphere. After 12 h (reaction progress monitored by TLC), the solvent was removed under reduced pressure and the residue diluted with distilled water and extracted thrice with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4 and concentrated to obtain the product. The crude product was purified by column chromatography with 25% ethyl acetate in hexane.

3-Phenyl-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one ( 6a )

Yield 82%, m.p. 213–215 °C; IR spectrum, ν, cm−1: 1233, 1672, 1716, 2971; 1H NMR (400 MHz, DMSO-d6): δ 5.22 (s, 2H, O–CH2), 6.95 (t, J = 7.5 Hz, 2H, H-ph), 7.31 (d, J = 7.4 Hz, 2H, H-ph), 7.48–7.74 (m, 8H, =CH, H-ph), 7.81–7.96 (m, 4H, =CH, H-ph), 8.15–8.31 (m, 8H, H-ph), 8.75–8.83 (m, 4H, H-ph), 8.90 (dd, J = 7.5, 1.4 Hz, 2H, H-ph), 8.98 (s, 1H, =CH of triazole); 13C NMR (100 MHz, DMSO-d6): δ 60.94, 114.38, 119.84, 123.08, 123.30, 126.33, 128.09, 128.30, 128.32, 128.39, 128.47, 128.50, 128.74, 129.12, 129.68, 130.03, 130.17, 130.20, 1230.46, 131.09, 134.45, 136.45, 136.74, 139.50, 140.01, 145.06, 149.94, 150.03, 157.93, 196.89; ESI–MS: m/z 676 (M + 1) observed for C45H33N5O2.

3-(4-Nitrophenyl)-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one ( 6b )

Yield 87%, m.p. 210–213 °C; IR spectrum, ν, cm−1: 1224, 1672, 1715, 3087; 1H NMR (400 MHz, DMSO-d6): δ 5.25 (s, 2H, O–CH2), 7.00 (d, J = 8.8 Hz, 2H, H-ph), 7.12–7.27 (m, 7H, H-ph), 7.28–7.31 (m, 3H, =CH, H-ph), 7.31–7.38 (m, 8H, H-ph), 7.48 (d, J = 7.4 Hz, 2H, H-ph), 7.81 (d, J = 6.9 Hz, 2H, H-ph), 7.98 (d, J = 11.8 Hz, 1H, =CH), 8.24 (d, J = 9.1 Hz, 2H, H-ph), 8.47 (d, J = 9.1 Hz, 2H, H-ph), 9.16 (s, 1H, =CH of triazole); 13C NMR (100 MHz, DMSO-d6): δ 60.51, 114.38, 119.73, 122.61, 123.10, 123.30, 126.30, 128.09, 128.26, 128.30, 128.40, 128.53, 128.69, 128.70, 128.74, 129.12, 129.68, 130.20, 130.46, 131.09, 134.45, 136.45, 136.74, 139.51, 140.00, 144.83, 145.03, 149.34, 149.51, 150.03, 157.89, 195.01; ESI–MS: m/z 721 (M + 1) observed for C45H32N6O4.

3-(4-Chlorophenyl)-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one ( 6c )

Yield 85%, m.p. 200–202 °C; IR spectrum, ν, cm−1: 1244, 1672, 1709, 3088; 1H NMR (400 MHz, DMSO-d6): δ 5.24 (s, 2H, O–CH2), 7.01 (d, J = 8.7 Hz, 2H, H-ph), 7.16–7.26 (m, 9H, H-ph), 7.27–7.30 (m, 3H, =CH, H-ph), 7.31–7.36 (m, 5H, H-ph), 7.50 (d, J = 7.5 Hz, 2H, H-ph), 7.61 (d, J = 11.7 Hz, 1H, =CH), 8.09 (d, J = 8.6 Hz, 2H, H-ph), 8.17 (d, J = 8.6 Hz, 2H, H-ph), 8.31–8.46 (m, 3H, H-ph), 9.08 (s, 1H, =CH of triazole); 13C NMR (100 MHz, DMSO-d6): δ 60.61, 114.40, 119.81, 122.61, 123.08, 123.30, 126.33, 128.10, 128.26, 128.30, 128.40, 128.53, 128.69, 128.70, 128.75, 129.12, 129.70, 130.21, 130.45, 131.10, 134.49, 134.51, 136.45, 136.76, 139.61, 140.03, 144.83, 149.35, 149.53, 150.03, 157.90, 195.20; ESI–MS: m/z 710 (M + 1) observed for C45H32ClN5O2.

3-(p-Tolyl)-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one ( 6d )

Yield 81%, m.p. 206–209 °C; IR spectrum, ν, cm−1: 1238, 1670, 1705, 3072; 1H NMR (400 MHz, DMSO-d6): δ 2.20 (s, 3H, CH3), 5.27 (s, 2H, O–CH2), 7.11–7.36 (m, 5H, =CH and H-ph), 7.36–7.53 (m, 3H, =CH, H-ph), 7.56 (d, J = 7.9 Hz, 2H, H-ph), 7.58–7.85 (m, 10H, =CH, H-ph), 7.92–8.06 (m, 3H, H-ph), 8.18 (d, J = 6.2 Hz, 2H, H-ph), 8.31 (d, J = 7.8 Hz, 2H, H-ph), 8.50 (d, J = 7.9 Hz, 2H, H-ph), 8.66 (s, 1H, =CH of triazole); ESI–MS: m/z 690 (M + 1) observed for C46H35N5O2.

3-(4-Methoxyphenyl)-1-(4-(4-((4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phen- yl)prop-2-en-1-one ( 6e )

Yield 80%, m.p. 200–202 °C; IR spectrum, ν, cm−1: 1244, 1672, 1709, 2977; 1H NMR (400 MHz, DMSO-d6): δ 3.72 (s, 3H, OCH3), 5.30 (s, 2H, O–CH2), 7.09 (d, J = 9.7 Hz, 2H, H-ph), 7.20 (d, J = 7.5 Hz, 2H, H-ph), 7.29–7.40 (m, 3H, =CH, H-ph), 7.49 (d, J = 8.1 Hz, 2H, H-ph), 7.55–7.80 (m, 7H, =CH, H-ph), 7.81–7.99 (m, 5H, H-ph), 8.00–8.15 (m, 4H, H-ph), 8.20 (d, J = 8.9 Hz, 2H, H-ph), 8.45 (d, J = 8.2 Hz, 2H, H-ph), 9.09 (s, 1H, =CH of triazole); ESI–MS: m/z 706 (M + 1) observed for C46H35N5O3.

1-(4-(4-((2-Methoxy-4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)-3-phenyl prop-2-en-1-one ( 6f )

Yield 80%, m.p. 210–212 °C; IR spectrum, ν, cm−1: 1243, 1672, 1710, 2985; 1H NMR (400 MHz, DMSO-d6): δ 3.84 (s, 3H, OCH3), 5.25 (s, 2H, O–CH2), 7.00 (d, J = 7.5 Hz, 1H, =CH), 7.07–7.24 (m, 4H, H-ph), 7.30–7.46 (m, 12H, H-ph), 7.53–7.62 (m, 5H, H-ph), 7.85 (d, J = 7.4 Hz, 2H, H-ph), 7.92 (dd, J = 7.3, 1.4 Hz, 2H, H-ph), 8.05 (d, J = 7.5 Hz, 2H, H-ph), 8.29 (d, J = 13.2 Hz, 1H, =CH), 8.91 (s, 1H, =CH of triazole); 13C NMR (100 MHz, DMSO-d6): δ 55.04, 60.01, 113.71, 114.12, 119.13, 122.09, 122.50, 125.33, 127.08, 127.30, 127.32, 127.38, 127.45, 127.50, 127.81, 128.15, 128.71, 129.03, 129.14, 129.20, 129.46, 130.09, 133.45, 135.12, 135.53, 138.62, 139.14, 144.63, 149.01, 149.53, 150.13, 158.01, 196.58; ESI–MS: m/z 706 (M + 1) observed for C46H35N5O3.

1-(4-(4-((2-Methoxy-4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)-3-(4-nitrophenyl)prop-2-en-1-one ( 6g )

Yield 86%, m.p. 196–198 °C; IR spectrum, ν, cm−1: 1236, 1672, 1711, 2975; 1H NMR (400 MHz, DMSO-d6): δ 3.76 (s, 3H, OCH3), 5.23 (s, 2H, O–CH2), 7.01 (d, J = 8.7 Hz, 2H, H-ph), 7.16–7.26 (m, 7H, H-ph), 7.30 (d, J = 7.9 Hz, 2H, H-ph), 7.32–7.38 (m, 7H, H-ph), 7.50 (d, J = 7.5 Hz, 2H, H-ph), 8.09 (d, J = 8.6 Hz, 2H, H-ph), 8.17 (d, J = 8.6 Hz, 2H, H-ph), 8.49 (d, J = 11.6 Hz, 1H, =CH), 8.56 (d, J = 9.6 Hz, 1H, =CH), 8.86 (d, J = 7.9 Hz, 2H, H-ph), 9.03 (s, 1H, =CH of triazole); ESI–MS: m/z 751 (M + 1) observed for C46H34N6O5.

3-(4-Chlorophenyl)-1-(4-(4-((2-methoxy-4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)prop-2-en-1-one ( 6h )

Yield 81%, m.p. 205–207 °C; IR spectrum, ν, cm−1: 1241, 1671, 1712, 3093; 1H NMR (400 MHz, DMSO-d6): δ 3.78 (s, 3H, OCH3), 5.23 (s, 2H, O–CH2), 7.00 (d, J = 8.0 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H, =CH), 7.27 (d, J = 7.3 Hz, 2H, H-ph), 7.46–7.53 (m, 9H, H-ph), 7.54–7.68 (m, 10H, H-ph), 7.77 (d, J = 7.3 Hz, 2H, H-ph), 8.03 (d, J = 8.7 Hz, 2H, H-ph), 8.10 (d, J = 11.7 Hz, 1H, =CH), 8.54 (s, 1H, =CH of triazole); ESI–MS: m/z 440 (M + 1) observed for C46H34ClN5O3.

1-(4-(4-((2-Methoxy-4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)-3-(p-tolyl)prop-2-en-1-one ( 6i )

Yield 76%, m.p. 180–183 °C; IR spectrum, ν, cm−1: 1241, 1671, 1712, 3093; 1H NMR (400 MHz, DMSO-d6): δ 2.23 (s, 3H), 3.75 (s, 3H, OCH3), 5.24 (s, 2H, O–CH2), 7.00 (d, J = 7.7 Hz, 1H, =CH), 7.08 (d, J = 7.7 Hz, 2H, H-ph), 7.17–7.24 (m, 3H, H-ph), 7.25–7.43 (m, 10H, H-ph), 7.49–7.59 (m, 5H, H-ph), 7.75 (d, J = 7.4 Hz, 2H, H-ph), 7.84 (dd, J = 7.3 Hz, 1.4 Hz, 2H, H-ph), 7.95 (d, J = 7.7 Hz, 2H, H-ph), 8.20 (d, J = 11.9 Hz, 1H, =CH), 8.51 (s, 1H, =CH of triazole); 13C NMR (100 MHz, DMSO-d6): δ 21.10, 54.96, 60.91, 113.43, 114.08, 119.91, 120.60, 122.95, 123.37, 123.50, 125.78, 126.91, 127.70, 128.20, 128.41, 128.55, 128.80, 129.10, 129.20, 129.70, 131.70, 132.57, 133.56, 133.98, 135.20, 138.50, 139.40, 139.50, 142.15, 144.71, 147.90, 149.46, 150.46, 150.13, 157.95, 196.90; ESI–MS: m/z 720 (M + 1) observed for C47H37N5O3.

1-(4-(4-((2-Methoxy-4-(1,4,5-triphenyl-1H-imidazol-2-yl)phenoxy)methyl)-1H-1,2,3-triazol-1-yl)phenyl)-3-(4-methoxyphenyl)prop-2-en-1-one ( 6j )

Yield 82%, m.p. 196–197 °C; IR spectrum, ν, cm−1: 1222, 1670, 1711, 2982; 1H NMR (400 MHz, DMSO-d6): δ 3.78 (s, 3H, OCH3), 3.81 (s, 3H, OCH3), 5.29 (s, 2H, O–CH2), 7.05 (d, J = 9.7 Hz, 1H, =CH), 7.14 (d, J = 7.5 Hz, 2H, H-ph), 7.33–7.27 (m, 3H, H-ph), 7.44 (d, J = 9.1 Hz, 1H, =CH), 7.73–7.50 (m, 8H, H-ph), 7.94–7.75 (m, 5H, H-ph), 8.09–7.95 (m, 4H, H-ph), 8.14 (d, J = 8.9 Hz, 2H, H-ph), 8.39 (d, J = 8.2 Hz, 2H, H-ph), 8.99 (s, 1H, =CH of triazole); ESI–MS: m/z 736 (M + 1) observed for C47H37N5O4.