Introduction

Quinoline molecules are present commonly in living organisms as important secondary metabolites [1], whereas 1,2,3-triazoles, chemically inert compounds, have not been detected in naturally occurring products [2]. The attachment of quinoline to 1,2,3-triazole skeletons in diverse and numerous ways, would yield valuable biomolecules for drug development. Moreover, 1,2,3-triazole can act as pharmacophores and linkers between quinoline and other pharmacophoric molecules that of interest in molecular hybridization approaches [3, 4].

Due to the large number of diseases, scientists tend to synthesize homogeneous and heterogeneous ring compounds that treated many of these diseases. One class of these compounds is 2-quinolones [5], which have received considerable attention in recent years because of their pharmacological [6] importance and various biological activities [7]. They possess antimicrobial [8], antifungal [9], anticancer [10], anti-HIV [11], anti-oxidant [12], enzyme inhibitory [13], and cytotoxic activities [14]. A second type of these compounds is 1,2,3-triazoles, which have assorted biological activities such as antibacterial, anti-tubercular, anticancer, antifungal, anti-tubercular, and which like 2-quinolones have anti-HIV properties [15, 16]. After development of the copper-catalyzed [3 + 2] cycloaddition of organic azides at terminal alkynes under mild conditions, the importance and wide application of 1,2,3-triazole compounds have increased significantly [17, 18]. Regioselective formation of 1,2,3-triazoles has proved to be the best example of click chemistry [19] and has found extensive applications in manifold domains of chemistry [20, 21]. Cu-catalyzed [3 + 2] cycloadditions of azides and alkynes (Meldal-Sharpless ‘click’ reaction) to give 1,2,3-triazoles have been used extensively together with a variety of functions to biomolecules [22,23,24]. Previously, it was reported on the selective synthesis of 1,2,3-triazole systems via non-catalyzed azide/acetylene [3 + 2] cycloadditions that are possible in the case of electrophilic activate acetylene derivatives [25]. Aly et al. reported the synthesis of ethyl pyrano[3,2-c]quinoline-4-carboxylates [26] and spiro(indoline-3,4′-pyrano[3,2-c]-quinoline)-3′-carbonitriles [27]. Besides that we have reported on one-pot synthesis of 2,3-bis(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)succinates and arylmethylene-bis(3,3′-quinoline-2-ones) [28]. Moreover, two series of N-2,3-bis(6-substituted-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-naphthalene-1,4-diones and substituted N-(methyl/ethyl)bis-quinolinone triethylammonium salts were synthesized. The synthesized compounds were targeted as candidates to extracellular signal-regulated kinases 1/2 (ERK1/2) with considerable antineoplastic activity [29]. In a very recent approach, design and synthesis of novel series of fused naphthofuro[3,2-c]quinoline-6,7,12-triones and pyrano[3,2-c]quinoline-6,7,8,13-tetraones as potential ERK inhibitors were reported [30]. The new inhibitors were synthesized and identified by different spectroscopic techniques and X-ray crystallography. They were evaluated for their ability to inhibit ERK1/2 in an in vitro radioactive kinase assay [30]. In this paper, we design to synthesize products that combine the qualities of each of them together in one molecule by applying click-chemistry techniques between 4-azidoquinolin-2(1H)-ones and different terminal alkynes. We hope that the aforementioned stuff shows prospective biological activities.

Results and discussion

Herein, we report the cycloaddition of 4-azidoquinolin-2(1H)-ones 1a–1d with ethyl propiolate (2) to give, in good to excellent yields, the corresponding ethyl 1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylates 3a–3d (Scheme 1), under the reaction conditions CuSO4/sodium ascorbate/DMF. The mixture of alkyne 2 with sodium ascorbate, CuSO4, and 4-azido compounds 1a–1d was gently heated for 12 h.

scheme 1

The solids of 1,2,3-triazoles 3a–3d were appeared as colorless products. Their structures were confirmed by different spectroscopic methods such as elemental analyses, IR, and NMR (1H, 13C, HMBC, HSQC, and 15N) and in addition to mass spectrometry were in good agreement with the assigned product structures. The elemental analyses and the mass spectra showed that compounds 3a–3d are formed from one molecule of 4-azidoquinolin-2(1H)-one 1a–1d and another of ethyl propiolate (2). Compounds 3a–3c exhibited NH stretching in IR spectra at \(\bar{\nu }\) = 3139–3127 cm−1, but compound 3d did not. Other major features of the IR spectra of 3a–3d were two carbonyl bands at \(\bar{\nu }\) = 1740–1717 cm−1 and 1677–1665 cm−1 for quinolinone-C-2 and ester carbonyls, respectively, which were further confirmed by 13C NMR spectrum data which exhibited signals at δC = 159.10–160.84 ppm for C-2 and 158.82–159.94 ppm for C-4a′.

Compound 3a which was assigned as ethyl 1-(6-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylate (Fig. 1) has spectral data as shown in Table 1. The 1H NMR of compound 3a as an example showed methyl protons H-4c′ as a triplet signal at δH = 1.35 ppm with coupling constant J = 7.1 Hz, which was confirmed from 13C NMR at δC = 14.16 ppm. H-4c′ gives COSY correlation, and C-4c′ gives HMBC correlation to the methylene protons H-4b′ as quartet at δH = 4.39 ppm with coupling constant J = 7.1 Hz; the attached carbon appears at δC = 60.88 ppm. Also, H-4b′ gives HMBC correlation with carbonyl carbon C-4a′ at δC = 159.91 ppm. Furthermore, the 1H NMR of compound 3a showed a broad singlet at δH = 12.33 ppm, due to quinoline-NH. On the other hand, the 13C NMR spectrum of compound 3a showed signals at δC = 160.84, 131.11, 114.47, and 60.88 ppm, which were assigned as C-2, C-5′, C-4a, and C-4b′, respectively.

Fig. 1
figure 1

Distinctive carbons of ethyl 1-(6-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylate (3a)

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Table 1 Spectroscopic data of compound 3a
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Based on these results, we applied similar methodology to other terminal alkynes, by allowing 4-(prop-2-yn-1-yloxy)benzaldehyde (4a) or 1-[4-(prop-2-yn-1-yloxy)phenyl]ethanone (4b) to react with 4-azidoquinolin-2(1H)-ones 1a–1d (Scheme 2). To illustrate our results, NMR (1H, 13C, 1H-1H COSY, HMBC, HSQC, and 15N) was performed for all the obtained products. As an example of the NMR, spectroscopic data of compound 5a (Fig. 2) are illustrated in Table 2.

scheme 2
Fig. 2
figure 2

Distinctive carbons of 4-[[(1-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]methoxy]benzaldehyde (5a)

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Table 2 Spectroscopic data of compound 5a
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We choose compound 5a as an example to confirm the structures. Elemental analysis and mass spectrometry show that compound 5a has gross formula C19H14N4O3 which comes from the reaction of one mole of 4-azidquinoline-2(1H)-one (1a) with one mole of 4-(prop-2-yn-1-yloxy)benzaldehyde (4a) (Fig. 2). The IR spectra of compound 5a showed signals at \(\bar{\nu }\) = 3124 cm−1, due to NH stretching, 2829 cm−1 for aliph.-CH, 1691, 1669 cm−1 due to two carbonyl groups, in addition to the aromatic absorption bands (Fig. 3). Further, the 1H NMR spectrum (DMSO-d6) (Table 2), for compound 5a, showed signals at δH = 12.29, 9.91, 8.92 ppm, due to quinoline-NH, CH=O, and triazole-H-5′, respectively. Two signals appeared as singlet at δH = 6.87 and 5.44 ppm, which were assigned as quinoline-H-3 and methyl group H-4a′, respectively. 13C NMR spectrum for compound 5a showed two downfield signals at δC = 191.33 and 162.84 ppm which were assigned as CH=O and C-4, respectively. Furthermore, other signals at δC = 126.85, 117.79, 114.42, and 61.20 ppm were assigned as C-5′, C-3, C-4a, and C-4a′, respectively, in addition to aromatic signals.

Fig. 3
figure 3

Distinctive carbons of 4-[4-[(4-acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl]-1-methylquinolin-2(1H)-one (5h)

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Similarly, the compound 5h comes from the reaction of equimolar amounts of 4-azido-1-methylquinolin-2(1H)-one (1d) and 1-[4-(prop-2-yn-1-yloxy)phenyl]ethanone (4b) (Fig. 3).

To confirm the structures of all obtained products, we chose focused the network coupling of compound 5h (Table 3). The C–CH3 singlet is distinctive at δH = 2.54 ppm and is assigned as H-b; the attached carbon appears at δC = 26.41 ppm. H-b gives HMBC correlation with a carbon at δC = 196.30 ppm, assigned as C-a, and a carbon at δC = 130.28 ppm, assigned as C-i. C-a gives HMBC correlation with a 2H doublet at δH = 7.98 ppm, assigned as H-o; this is a three-bond coupling. The attached carbon appears at δC = 130.48 ppm. H-o gives COSY correlation and C-i gives HMBC correlation, with the other 2H doublet at δH = 7.23 ppm, assigned as H-m; the attached carbon appears at δC = 114.61 ppm. The correlation between C-i and H-m is another three-bond correlation. Both H-o and H-m give HMBC correlation with a carbon at δC = 161.75 ppm, assigned as C-p. Further, C-p gives HMBC correlation with a 2H singlet at δH = 5.41 ppm, assigned as H-4a′; the attached carbon appears at δC = 61.07 ppm. H-4a′ gives HMBC correlation with a protonated carbon at δC = 127.01 ppm, assigned as C-5′; the attached proton appears at δH = 8.90 ppm. H-4a′ also gives HMBC correlation with one of the two non-protonated carbons at δC = 142.76 and 142.57 ppm, assigned as C-4′, and with the sp2 nitrogen at δN = 358.10 ppm, assigned as N-3′.

Table 3 Spectroscopic data of compound 5 h
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The other sp2 nitrogen, N-2′, is not observed. H-5′ gives HMBC correlation with a nitrogen at δN = 246.8 ppm, assigned as N-1′. N-1′ gives HMBC correlation with the 1H singlet at δH = 7.00 ppm, assigned as H-3; the attached carbon appears at δC = 117.27 ppm. Also, H-3 gives HMBC correlation with the other of the two carbons at δC = 142.76 and 142.57 ppm, assigned as C-4; and with the non-protonated one of the two carbons at δC = 115.60 and 115.50 ppm, presumably the smaller line at δC = 115.50 ppm, which is assigned as C-4a. H-3 also gives HMBC correlation with the sp3 nitrogen at δN = 151.3 ppm, assigned as N-1. N-1 gives HMBC correlation with the methyl singlet at δH = 3.73 ppm, assigned as H-1a; the attached carbon appears at δC = 29.59 ppm. H-1a gives HMBC correlation with carbons at δC = 160.27 ppm, assigned as C-2, and δC = 140.12 ppm, assigned as C-8a; both of these are three-bond correlations. C-8a gives HMBC correlation with a 1H doublet at δH = 7.45 ppm, assigned as H-5, and a 1H “triplet” at δH = 7.79 ppm, assigned as H-7; both of these are also three-bond correlations. The attached carbons appear at δC = 124.41 (C-5) and 132.35 ppm (C-7). The remaining protons of the four-spin benzene system are a 1H doublet at δH = 7.74 ppm, assigned as H-8, and a 1H “triplet” at δH = 7.35 ppm, assigned as H-6; the attached carbons appear at δC = 115.60 (C-8) and 122.75 ppm (C-6). H-6 and H-8 give HMBC correlation with C-4a; both of these are three-bond correlations.

The formation of products 3 and 5 via click reaction can be rationalized as shown in Scheme 3. First stage, Cu(II), was reduced by sodium ascorbate into Cu(I) which then replaced the alkyne-H proton to form Cu-salt (A). Secondly, nucleophilic addition of (A) to the aromatic azides 1a–1d to form the intermediate (B) was accompanied by the loss of catalyzed Cu(I) that was followed by inter-nucleophilic cyclization to give adduct (C). Finally, reduction of adduct (C) with hydrogen proton leads to the formation of 3a–3d and 5a–5h. The mechanism was totally supported via literature [31].

scheme 3

Conclusion

The reactions of 4-azidoquinolin-2(1H)-ones with some terminal alkynes to obtain new quinolin-2-one-linked 1,2,3-triazoles are useful examples of Cu-catalyzed [3 + 2]cycloaddition of azides and alkynes (click reaction); all structures were established by spectroscopic analysis.

Experimental

Melting points were determined using open glass capillaries on a Gallenkamp melting point apparatus (Weiss–Gallenkamp, Loughborough, UK). The IR spectra were recorded from potassium bromide disks with an FT device, Faculty of Science Minia University. NMR spectra were measured in DMSO-d6 on a Bruker AV-400 spectrometer (400 MHz for 1H, 100 MHz for 13C, and 40.55 MHz for 15N); chemical shifts are expressed in δ (ppm) versus internal tetramethylsilane (TMS) = 0 ppm for 1H and 13C, and external liquid ammonia = 0 ppm for 15N. Coupling constants are stated in Hz. Correlations were established using 1H-1H COSY, and 1H-13C, and 1H-15N HSQC and HMBC experiments. Mass spectra were recorded on a Finnigan Fab 70 eV, Institute of Organic Chemistry, Karlsruhe University, Karlsruhe, Germany. TLC was performed on analytical Merck 9385 silica aluminum sheets (Kieselgel 60) with Pf254 indicator; TLCs were viewed at λmax = 254 nm. Elemental analyses were carried out on Perkin device at the Microanalytical Institute of Organic Chemistry, Karlsruhe University, Karlsruhe, Germany.

4-Azidoquinoline-2(1H)-ones 1a–1d were prepared according to the literature [32, 33]. Ethyl propiolate (2) was used as received (Aldrich), and 4-(prop-2-yn-1-yloxy)benzaldehyde (4a) and 1-[4-(prop-2-yn-1-yloxy)phenyl]ethanone (4b) were prepared according to the literature [34].

General procedure for the formation of compounds 3a–3d and 5a–5h

A mixture of terminal alkynes 2 or 4a, 4b (1.0 mmol) in 20 cm3 dimethyl formamide (DMF), 5 cm3 H2O, sodium ascorbate (0.4 mmol), and CuSO4·5H2O (0.2 mmol) was stirred for 5 min at room temperature. Then, 4-azido compounds 1a–1d (1.0 mmol) were added to the mixture. The reaction mixture was allowed to stir at 30–50 °C for 12 h, and another portion of sodium ascorbate (0.4 mmol) was added and the reaction was monitored with TLC. After completion, the mixture was concentrated, diluted with H2O, and extracted with CH2Cl2 (3 × 15 cm3). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The products were recrystallized from absolute ethanol.

Ethyl 1-(2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylate (3a, C14H12N4O3)

Colorless crystals; yield: 0.220 g (77%); m.p.: 252–254 °C; IR: \(\bar{\nu }\) = 3137 (NH), 3075 (Ar–H), 2966–2850 (Ali-H), 1717, 1677 (CO), 1610 (C=C) cm−1; 1H NMR: δ = 12.33 (s, 1H, NH), 9.39 (s, 1H, H-5′), 7.66 (t, 1H, J = 7.3 Hz, H-7), 7.48 (d, 1H, J = 8.2 Hz, H-8), 7.38 (d, 1H, J = 8.0 Hz, H-5), 7.25 (t, 1H, J = 7.6 Hz, H-6), 6.95 (s, 1H, H-3), 4.39 (q, 2H, J = 7.1 Hz, H-4b′), 1.35 (t, 3H, J = 7.1 Hz, H-4c′) ppm; 13C NMR: δ = 160.84 (C-2), 195.91 (C-4a′), 143.16 (C-8a′), 139.30, 139.22 (C-4,4′), 132.00 (C-7), 131.11 (C-5′), 123.90 (C-5), 122.68 (C-6), 118.76 (C-3), 115.86 (C-8), 114.47 (C-4a), 60.88 (C-4b′), 14.16 (C-4c′) ppm; 15N NMR: δ = 367.4 (N-2′/3′), 359.7 (N-3′/N-2′), 250.0 (N-1′), 152.4 (N-1) ppm; MS (FAB): m/z (%) = 284 (M+, 100).

Ethyl 1-(6-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylate (3b, C15H14N4O3)

Colorless crystals; yield: 0.240 (80%); m.p.: 251–253 °C; IR (KBr): \(\bar{\nu }\) = 3127 (NH), 3077 (Ar–H), 2983-2865 (Ali-H), 1719, 1675 (CO), 1609 (C=C) cm−1; 1H NMR: δ = 12.26 (s, 1H, NH), 9.36 (s, 1H, H-5′), 7.49 (d, J = 8.2 Hz, 1H, H-7), 7.38 (d, J = 8.3 Hz, 1H, H-8), 7.14 (s, 1H, H-5), 6.90 (s, 1H, H-3), 4.39 (q, J = 7.0 Hz, 2H, H-4b′), 2.30 (s, 3H, H-6a), 1.35 (t, J = 7.1 Hz, 3H, H-4c′) ppm; 13C NMR: δ = 160.69 (C-2), 159.94 (C-4a′), 143.00 (C-4), 139.22 (C-4′), 137.38 (C-8a), 133.31 (C-7), 131.91 (C-6), 131.09 (C-5′), 123.05 (C-5), 118.84 (C-3), 115.82 (C-8), 114.48 (C-4a), 60.86 (C-4b′), 20.44 (C-6a), 14.16 (C-4c′) ppm; 15N NMR: δ = 249.6 (N-1′), 247.9, 246.9 (N-2′,3′), 152.4 (N-1) ppm.

Ethyl 1-(6-methoxy-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylate (3c, C15H14N4O4)

Colorless crystals; yield: 0.230 g (73%); m.p.: 271–273 °C; IR (KBr): \(\bar{\nu }\) = 3139 (NH), 3075 (Ar–H), 2918–2853 (Ali-H), 1719, 1676 (CO), 1628 (C=N) cm−1; MS (FAB): m/z (%) = 314 (M+, 100); 1H NMR: δ = 12.23 (s, 1H, NH), 9.39 (s, 1H, H-5′), 7.43 (d, J = 9.0 Hz, 1H, H-8), 7.35 (dd, J = 9.0 Hz, 2.7 Hz, 1H, H-7), 6.93 (s, 1H, H-3), 6.86 (d, J = 2.6 Hz, 1H, H-5), 4.39 (q, J = 7.1 Hz, 2H, H-4b′), 3.71 (s, 3H, H-6a), 1.35 (t, J = 7.1 Hz, 3H, H-4c′) ppm; 13C NMR: δ = 160.35 (C-2), 159.93 (C-4a′), 154.56 (C-6), 142.63 (C-4), 139.27 (C-4′), 133.98 (C-8a), 131.05 (C-5′), 121.19 (C-7), 119.04 (C-3), 117.38 (C-8), 114.90 (C-4a), 105.50 (C-5), 60.87 (C-4b′), 55.48 (C-6a), 14.15 (C-4c′) ppm; 15N NMR: δ = 367.0, 360.2 (N-2′,3′), 250.3 (N-1′), 151.5 (N-1) ppm.

Ethyl 1-(1-methyl-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazole-4-carboxylate (3d, C15H14N4O3)

Colorless crystals; yield: 0.195 g (69%); m.p.: 269–271 °C; IR (KBr): \(\bar{\nu }\) = 3081 (Ar–H), 2984 (Ali-H), 1740, 1665 (CO), 1595 (C=C) cm−1; 1H NMR: δ = 9.41 (s, 1H, H-5′), 7.65 (“t”, J = 7.2 Hz, 1H, H-7), 7.49 (d, J = 8.1 Hz, 1H, H-8), 7.34 (d, J = 8.0 Hz, 1H, H-5), 7.28 (“t”, J = 7.4 Hz, 1H, H-6), 6.95 (s, 1H, H-3), 4.37 (q, J = 7.1 Hz, 2H, H-4b′), 2.50 (s, 3H, H-1a), 1.36 (t, J = 7.1 Hz, 3H, H-4c′) ppm; 13C NMR: δ = 159.10 (C-2), 158.82 (C-4a′), 141.12 (C-8a), 139.49, 139.45 (C-4,4′), 132.23 (C-7), 126.94 (C-5′), 122.22, 122.12 (C-5,6), 118.70 (C-3), 115.32 (C-8), 114.06 (C-4a), 61.58 (C-4b′), 29.40 (C-1a), 13.63 (C-4c′) ppm.

4-[[[1-(2-Oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]oxy]methyl]benzaldehyde (5a, C19H14N4O3)

Colorless crystals; yield 0.260 (71%); m.p.: 225–227 °C; IR (KBr): \(\bar{\nu }\) = 3124 (NH), 2859 (Ali-H), 1691, 1669 (CO), 1598 (C=C) cm−1; 1H NMR: δ = 12.29 (s, 1H, NH), 9.91 (s, 1H, CHO), 8.92 (s, 1H, H-5′), 7.92 (d, 2H, J = 8.5 Hz, H-o), 7.66 (t, 1H, J = 7.6 Hz, H-7), 7.48 (d, 1H, J = 8.9 Hz, H-8), 7.46 (d, 1H, J = 9.0 Hz, H-5), 7.32 (d, 2H, J = 8.5 Hz, H-m), 7.25 (t, 1H, J = 7.6 Hz, H-6), 6.87 (s, 1H, H-3), 5.44 (s, 2H, H-4a′) ppm; 13C NMR: δ = 191.33 (CHO), 162.84 (C-4), 160.95 (C-p), 143.57 (C-2), 142.61 (C-4′), 139.42 (C-8a), 131.91 (C-7), 131.79 (2C-o), 130.00 (C-i), 126.85 (C-5′), 123.93 (C-5), 122.60 (C-6), 117.79 (C-3), 115.27 (2C-m), 114.42 (C-4a), 61.20 (C-4a′) ppm; 15N NMR: δ = 247.7 (N-1′) ppm.

4-[[[1-(6-Methyl-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]oxy]methyl]benzaldehyde (5b, C20H16N4O3)

Colorless crystals; yield: 0.3 g (83%); m.p.: 220–222 °C; IR (KBr): \(\bar{\nu }\) = 3135 (NH), 2950 (Ali-H), 1690, 1669 (CO), 1595 (C=C) cm−1; 1H NMR: δ = 12.22 (s, 1H, NH), 9.91 (s, 1H, CH = O), 8.90 (s, 1H, H-5′), 7.92 (AA′XX′, JAA′ = 3.6 Hz, JAX = 10.0 Hz, JAX′ = 1.2 Hz, 2H, H-m), 7.49 (dd, J = 8.5 Hz, 1.6 Hz, 1H, H-7), 7.39 (d, J = 8.4 Hz, 1H, H-8), 7.32 (AA′XX′, JAX = 10.0 Hz, JAX′ = 1.2 Hz, JXX′ = 0.9 Hz, 2H, H-o), 7.21 (bs, 1H, H-5), 6.82 (s, 1H, H-3), 5.44 (s, 2H, H-4a′), 2.30 (s, 3H, H-6a) ppm; 13C NMR: δ = 191.33 (CH=O), 162.81 (C-p), 160.80 (C-2), 143.36, 142.57 (C-4,4′), 137.51 (C-8a), 133.21 (C-7), 131.79 (C-m), 131.76 (C-6), 130.00 (C-i), 126.85 (C-5′), 123.09 (C-5), 117.82 (C-3), 115.91 (C-8), 115.28 (C-o), 114.36 (C-4a), 61.20 (C-4a′), 20.55 (C-6a) ppm; 15N NMR: δ = 364.6 (N-2′), 358.1 (N-3′), 247.7 (N-1′), 152.1 (N-1) ppm.

4-[[[1-(6-Methoxy-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]oxy]methyl]benzaldehyde (5c, C20H16N4O4)

Colorless crystals; yield: 0.220 g (58%); m.p.: 245–247 °C; IR (KBr): \(\bar{\nu }\) = 3144 (NH), 3067 (Ar–H), 2994, 2851 (Ali-H), 1674(CO), 1625 (C=N), 1592 (C=C) cm−1; 1H NMR: δ = 12.20 (s, 1H, NH), 9.90 (s, 1H, CH=O), 8.94 (s, 1H, H-5′), 7.91 (d, J = 8.6 Hz, 2H, H-o), 7.44 (d, J = 9.0 Hz, 1H, H-8), 7.34 (dd, J = 9.0 Hz, 2.3 Hz, 1H, H-7), 7.31 (d, J = 8.6 Hz, 2H, H-m), 6.90 (d, J = 2.0 Hz, 1H, H-5), 6.86 (s, 1H, H-3), 5.45 (s, 2H, H-4a′), 3.68 (s, 3H, H-6a) ppm; 13C NMR: δ = 191.33 (CH=O), 162.79 (C-p), 160.47 (C-2), 154.50 (C-6), 143.03, 142.68 (C-4,4′), 134.06 (C-8a), 131.79 (C-o), 129.99 (C-i), 126.75 (C-5′), 121.01 (C-7), 118.10 (C-3), 117.44 (C-8), 115.27 (C-m), 114.83 (C-4a), 105.53 (C-5), 61.19 (C-4a′), 55.38 (C-6a) ppm; 15N NMR: δ = 248.0 (N-1′), 151.3 (N-1) ppm.

4-[[[1-(1-Methyl-2-oxo-1,2-dihydroquinolin-4-yl)-1H-1,2,3-triazol-4-yl]oxy]methyl]benzaldehyde (5d, C15H14N4O3)

Colorless crystals; yield: 0.2 g (55%), m.p.: 268–270 °C; IR (KBr): \(\bar{\nu }\) = 2990, 2871 (Ali-H), 1687, 1665 (CO), 1585 (C = C) cm−1; MS (FAB): m/z (%) = 360 (M+, 100); 1H NMR: δ = 9.91 (s, 1H, CH=O), 8.91 (s, 1H, H-5′), 7.92 (AA′XX′, JAX = 8.8 Hz, JAA′ = 3.7 Hz, JXX′ = 0.9 Hz, 2H, H-o), 7.80 (d“t”, Jd = 1.4 Hz, J“t” = 7.8 Hz, 1H, H-7), 7.75 (d, J = 8.0 Hz, 1H, H-8), 7.45 (dd, J = 8.1 Hz, 1.2 Hz, 1H, H-5), 7.35 (d“t”, Jd = 1.1 Hz, J“t” = 7.0 Hz, 1H, H-6), 7.32 (d, J = 8.7 Hz, 2H, H-m), 7.01 (s, 1H, H-3), 5.44 (s, 2H, H-4a′), 3.73 (s, 3H, H-1a) ppm; 13C NMR: δ = 191.34 (CH=O), 162.84 (C-p), 160.27 (C-2), 142.62, 142.57 (C-4′,8a), 140.13 (C-4), 132.36 (C-7), 131.80 (C-o), 130.01 (C-i), 127.08 (C-5′), 124.40 (C-5), 122.76 (C-6), 117.30 (C-3), 115.61, 115.51 (C-4a,8), 115.27 (C-m), 61.20 (C-4a′), 29.59 (C-1a) ppm; 15N NMR: δ = 146.9 (N-1) ppm.

4-[4-[(4-Acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl]-quinolin-2(1H)-one (5e, C20H16N4O3)

Colorless crystals; yield: 0.280 g (78%); m.p.: 252–254 °C; IR (KBr): \(\bar{\nu }\) = 3166 (NH), 2944 (Ali-H), 1691, 1669 (CO), 1595 (C=C) cm−1; 1H NMR: δ = 12.29 (s, 1H, NH), 8.91 (s, 1H, H-5′), 7.97 (d, J = 8.7 Hz, 2H, H-o), 7.66 (“t”, J = 7.6 Hz, 1H, H-7), 7.48 (d, J = 8.6 Hz, 1H, H-8), 7.46 (d, J = 8.6 Hz, 1H, H-5), 7.25 (“t”, J = 7.5 Hz, 1H, H-6), 7.22 (d, J = 8.6 Hz, 2H, H-m), 6.86 (s, 1H, H-3), 5.41 (s, 2H, H-4a′), 2.54 (s, 3H, H-b) ppm; 13C NMR: δ = 196.29 (C-a), 161.74, 160.95 (C-p,2), 143.57, 142.75 (C-4′,4), 139.42 (C-8a), 131.90 (C-7), 130.47 (C-o), 130.28 (C-i), 126.78 (C-5′), 123.94 (C-5), 122.59 (C-6), 117.76 (C-3), 115.93 (C-8), 114.61 (C-m), 114.42 (C-4a), 61.07 (C-4a′), 26.40 (C-b) ppm; 15N NMR: δ = 364.4 (N-2′), 358.2 (N-3′), 247.3 (N-1′), 152.5 (N-1) ppm.

4-[4-[(4-Acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl]-6-methylquinolin-2(1H)-one (5f, C21H18N4O3)

Colorless crystals; yield: 0.360 g (89%); m.p.: 263-265 °C; IR (KBr): \(\bar{\nu }\) = 3165 (NH), 2950 (Ali-H), 1687, 1670 (CO), 1598 (C=C) cm−1; MS (FAB): m/z (%) = 374 (M+, 100); 1H NMR: δ = 12.22 (bs, 1H, NH), 8.89 (s, 1H, H-5′), 7.98 (d, J = 8.6 Hz, 2H, H–o), 7.49 (bd, J = 8.2 Hz, 1H, H-7), 7.39 (d, J = 8.5 Hz, 1H, H-8), 7.22 (d, J = 8.5 Hz, 2H, H-m), 7.21 (bs, 1H, H-5), 6.81 (s, 1H, H-3), 5.41 (s, 2H, H-4a′), 2.54 (s, 3H, H-b), 2.30 (s, 3H, H-6a) ppm; 13C NMR: δ = 196.28 (C-a), 161.71 (C-p), 160.80 (C-2), 143.36, 142.71 (C-4′,4), 137.51 (C-8a), 133.20 (C-7), 131.75 (C-6), 130.47 (C-o), 130.27 (C-i), 126.77 (C-5′), 123.09 (C-5), 117.79 (C-3), 115.91 (C-8), 114.61 (C-m), 114.35 (C-4a), 61.06 (C-4a′), 26.40 (C-b), 20.53 (C-6a) ppm; 15N NMR: δ = 364.1 (N-2′), 357.1 (N-3′), 247.3 (N-1′), 151.8 (N-1) ppm.

4-[4-[(4-Acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl]-6-methoxyquinolin-2(1H)-one (5g, C21H18N4O4)

Colorless crystals; yield 0.270 g (69%); m.p.: 253-255 °C; 1H NMR: δ = 12.20 (bs, 1H, NH), 8.93 (s, 1H, H-5′), 7.97 (d, J = 8.8 Hz, 2H, H–o), 7.43 (d, J = 9.0 Hz, 1H, H-8), 7.34 (dd, J = 9.0 Hz, 2.5 Hz, 1H, H-7), 7.22 (d, J = 8.8 Hz, 2H, H-m), 6.90 (d, J = 2.5 Hz, 1H, H-5), 6.85 (s, 1H, H-3), 5.41 (s, 2H, H-4a′), 3.68 (s, 3H, H-6a), 2.54 (s, 3H, H-b) ppm; 13C NMR: δ = 196.28 (C-a), 161.69 (C-p), 160.47 (C-2), 154.50 (C-6), 143.03, 142.83 (C-4′,4), 134.07 (C-8a), 130.46 (C-o), 130.27 (C-i), 126.67 (C-5′), 121.00 (C-5′), 118.06 (C-7), 117.44 (C-3), 114.83 (C-8), 114.61 (C-m), 105.53 (C-5), 61.06 (C-4a′), 55.37 (C-6a), 26.39 (C-b) ppm; 15N NMR: δ = 364.3 (N-2′), 358.1 (N-3′), 247.9 (N-1′), 151.3 (N-1) ppm.

4-[4-[(4-Acetylphenoxy)methyl]-1H-1,2,3-triazol-1-yl]-1-methylquinolin-2(1H)-one (5h, C21H18N4O3)

Colorless crystals; yield: 0.250 g (67%); m.p.: 218-220 °C; IR (KBr): \(\bar{\nu }\) = 2895 (Ali-H), 1679, 1667 (CO), 1598 (C=C) cm−1; 1H NMR: δ = 8.90 (s, 1H, H-5′), 7.98 (d, 2H, J = 8.6 Hz, H-o), 7.79 (t, 1H, J = 7.6 Hz, H-7), 7.74 (d, 1H, J = 8.4 Hz, H-8), 7.45 (d, 1H, J = 8.0 Hz, H-5), 7.35 (t, 1H, J = 7.4 Hz, H-6), 7.23 (d, 2H, J = 8.6 Hz, H-m), 7.00 (s, 1H, H-3), 5.41 (s, 2H, -4a′), 3.73 (s, 3H, H-1a), 2.54 (s, 3H, H-b) ppm; 13C NMR: δ = 196.30 (C-a), 161.75 (C-p), 160.27 (C-2), 142.76, 142.57 (C-4,4′), 140.12 (C-8a), 132.35 (C-7), 130.48 (2C-o), 130.28 (C-i), 127.01 (C-5′), 124.41 (C-5), 122.75 (C-6), 117.27 (C-3), 115.60 (C-8), 115.50 (C-4a), 114.61 (2C-m), 61.07 (C-4a′), 29.59 (C-1a), 26.41 (C-b) ppm; 15N NMR: δ = 358.1 (N-3′), 246.8 (N-1′), 148.0 (N-1) ppm; MS (FAB): m/z (%) = 374 (M+, 100).