Introduction

Quinolines are a very important class of alkaloids with a wide range of pharmacological and biological activities, such as antimicrobial [1], antiproliferative [2], and antituberculosis activities [3]. It has been reported that some of them were used as DNA methylation modulators for the treatment of cancer and hematological disorders [4], and as antimalarial agents in the treatment of malarial infections [5]. Quinidine is a well-known example of quinoline alkaloids (Fig. 1, left) [6], a pharmaceutical agent that acts as a class I antiarrhythmic agent (Ia) in the heart. It is widely used for treatment of life–threatening Plasmodium falciparum malaria and ventricular arrhythmias. Another important drug is Chloroquine (Fig. 1, right) [7]; it was discovered in 1934 by Hans Andersag and coworkers at the laboratories of Bayer. The United States government-sponsored clinical trials for antimalarial drug development showed unequivocally that chloroquine has a significant therapeutic value as an antimalarial drug. Accordingly, novel strategies for the synthesis of quinolines continued to receive considerable attention in the field of organic synthetics chemistry [8–13].

Fig. 1
figure 1

The interesting drugs containing quinoline analogues

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Ionic liquids have attracted increasing interest in the context of green chemistry in the past few years. They were initially introduced as alternative green reaction media because of their unique chemical and physical properties of nonvolatility, nonflammability, thermal stability, and controlled miscibility [14, 15]. The possibility of recycling them also ensured their utility in organic synthesis as green solvents for a large number of organic transformations [16].

As a continuation of our research devoted to the development of new methods for the preparation of heterocycles in ionic liquids [17–21], we would like to report the synthesis of 4-arylquinoline-3-carbonitrile and 4-arylbenzo[h]quinoline-3-carbonitrile derivatives under catalyst-free conditions. The method involved a three-component reaction of aldehyde, (E)-3-aminobut-2-enenitrile and dimedone or 2-hydroxynaphthalene-1,4-dione in ionic liquids.

Results and discussion

Treatment of aldehyde 1, (E)-3-aminobut-2-enenitrile 2, and 5,5-dimethyl-1,3-cyclohex-2-ene (dimedone) 3 in ionic liquid [BMIm]Br at 50 °C, resulted in the corresponding 1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxo-4-arylquinoline-3-carbonitrile derivatives 4a–k in high yields (Scheme 1).

Scheme 1
scheme 1

The reaction of 1, 2, and 3

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Using the conversion of benzaldehyde 1a, (E)-3-aminobut-2-enenitrile 2 and 3 as a model reaction, different temperatures and ionic liquids were explored to obtain an optimal condition, as shown in Table 1. The product 4a was not detected in ionic liquids at room temperature (Table 1, Entry 1), and was obtained successfully in higher reaction temperature, reaching a maximum of 92 % yield at 50°C (Table 1, entries 2-4). Different imidazolium ionic liquids were also tested, and [BMIm]Br appeared to be the best solvent for this transformation (entry 3 vs. 5–9). Acidic ionic liquids, such as [BMIm][HSO4], or acidic catalysts, for example, TsOH and AgOTf, were used to further improve the yields of the product 4a, to our disappointed, the results are not good (Table 1, entries 10–12).

Table 1 Synthetic results of 4a under different reaction conditions
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After reaction completion as monitored by TLC, products were isolated by simple filtration after the addition of a small amount of water to the cooled reaction mixture. Water in the filtrate was removed by distillation under reduced pressure, and the [BMIm]Br in the residue could be reused after being evaporated at 80°C for 4 h in vacuum. Successive reuse of the recycled ionic liquid of [BMIm]Br in the model reaction gave high yields of 4a (90 %) even after the fourth cycle.

Subsequently, the optimized conditions were applied for the conversion of various kinds of aldehydes into the corresponding 4-arylquinoline-3-carbonitrile analogues 4a–k in high yields (Table 2, entries 1–11). The results are summarized in Table 2. It is observed that the process can tolerate both electron-donating (alkyl and alkoxy) and electron-withdrawing (halogen) substituents in the benzaldehydes. In all cases, the reactions proceeded efficiently at 50°C under mild conditions to afford the corresponding products in high yields.

Table 2 Synthetic results of 4a–k in ionic liquids
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In our continued study, it was found that 2-hydroxynaphthalene-1,4-dione 5 also gave the satisfied results, if it was used as an 1,3-dicarbonyl compound to react with 1 and 2 under the same reaction conditions (Scheme 2), and resulted another series of novel 1,4,5,6-tetrahydro-2-methyl-5,6-dioxo-4-arylbenzo[h]quinoline-3-carbonitriles 6 in high yields (Table 3). All the products of 4a–k and 6a–k were characterized by 1H NMR, IR and HRMS, and the data were in good agreement with the preconceived structures.

Scheme 2
scheme 2

Reaction of 1, 3, and 5

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Table 3 Synthetic results of 6a–k in ionic liquids
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According to the product structures of 4 and 6, we think that subsequent Knoevenagel condensation, Michael addition, intra-molecular cyclization, and dehydration reaction may take place; the possible reaction mechanism is outlined in Scheme 3.

Scheme 3
scheme 3

The possible reaction mechanism

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Experimental

Melting points were determined in open capillaries and are uncorrected. IR spectra were recorded on a Tensor 27 spectrometer in KBr pellet. NMR spectra were obtained from a solution in DMSO-d 6 or CDCl3 with Me4Si as internal standard using a Bruker-400 spectrometer. HRMS analyses were carried out using a Bruker-micro-TOF-Q-MS analyzer.

General procedure for the synthesis of quinoline and benzo[h]quinoline derivatives 4 and 6

A dry 50-ml flask was charged with aldehyde 1 (1.0 mmol), (E)-3-aminobut-2-enenitrile 2 (82 mg, 1.0 mmol), dimedone (144 mg, 1.0 mmol) 3 or 2-hydroxynaphthalene-1,4-dione 5 (174 mg, 1.0 mmol) and ionic liquid [BMIm]Br (2 ml). The reaction mixture was stirred at 50°C for 6–14 h, and then a small amount of water (5 ml) was added to the mixture, and the generated yellow solid was filtered off. The water in the filtrate was removed by distillation under reduced pressure, and the ionic liquid in the residue could be reusable by being evaporated at 80 °C for 4 h at vacuum. The crude yellow products were washed with water and purified by recrystallization from 95 % EtOH, then dried at 80 °C for 2 h under vacuum to give 4 or 6.

1,4,5,6,7,8-Hexahydro-2,7,7-trimethyl-5-oxo-4-phenylquinoline-3-carbonitrile 4a: M. p. 236–238 °C, (Lit [22].: 232–234 °C); 1H NMR (DMSO-d 6, 400 MHz): δ H 0.92 (s, 3H, CH3), 1.02 (s, 3H, CH3), 1.99 (d, J = 16.4 Hz, 1H, CH), 2.06 (s, 3H, CH3), 2.18 (d, J = 16.4 Hz, 1H, CH), 2.34 (d, J = 17.2 Hz, 1H, CH), 2.43 (d, J = 17.2 Hz, 1H, CH), 4.41 (s, 1H, CH), 7.17–7.20 (m, 3H, ArH), 7.27–7.31 (m, 2H, ArH), 9.44 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): δ C 18.4, 27.5, 29.3, 32.6, 38.4, 41.1, 50.6, 89.0, 109.7, 119.2, 127.1, 127.5, 128.6, 144.4, 144.7, 148.4, 195.4. IR (KBr): ν 3,288, 3,072, 2,962, 2,930, 2,885, 2,811, 2,751, 2,204, 1,659, 1,608, 1,490, 1,469, 1,382, 1,341, 1,319, 1,260, 1,148 cm−1. HRMS (ESI, m/z): Calcd for C19H19N2O [M–H]− 291.1498, found 291.1499.

4-(2-chlorophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4b: M. p. 245–247 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.94 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.99 (d, J = 16.0 Hz, 1H, CH), 2.03 (s, 3H, CH3), 2.17 (d, J = 16.0 Hz, 1H, CH), 2.33 (d, J = 17.2 Hz, 1H, CH), 2.44 (d, J = 17.2 Hz, 1H, CH), 4.74 (s, 1H, CH), 7.09–7.24 (m, 4H, ArH), 9.50 (s, 1H, NH). IR (KBr): ν 3,240, 3,189, 3,077, 2,962, 2,931, 2,895, 2,880, 2,203, 1,660, 1,607, 1,489, 1,471, 1,457, 1,435, 1,383, 1,261, 1,222, 1,149, 751 cm−1. HRMS (ESI, m/z): Calcd for C19H18ClN2O [M - H]− 325.1108, found 325.1098.

4-(4-Chlorophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4c: M. p. 253–255 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.91 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.01 (d, J = 16.4 Hz, 1H, CH), 2.07 (s, 3H, CH3), 2.18 (d, J = 16.4 Hz, 1H, CH), 2.33 (d, J = 17.2 Hz, 1H, CH), 2.42 (d, J = 17.2 Hz, 1H, CH), 4.44 (s, 1H, CH), 7.20 (d, J = 8.4 Hz, 2H, ArH), 7.36 (d, J = 8.4 Hz, 2H, ArH), 9.50 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): δ C 18.5, 27.4, 29.2, 32.6, 38.0, 41.2, 50.5, 88.7, 109.6, 118.9, 128.7, 129.0, 132.8, 143.2, 144.5, 147.9, 195.1. IR (KBr): ν 3,242, 3,190, 3,078, 2,961, 2,881, 2,810, 2,749, 2,360, 2,200, 1,658, 1,610, 1,491, 1,435, 1,391, 1,317, 1,258, 1,147, 1,126, 1,089, 1,015, 972, 847 cm−1. HRMS (ESI, m/z): Calcd for C19H18ClN2O [M–H]− 325.1108, found 325.1095.

4-(4-Bromophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4d: M. p. 204–206 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.91 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.01 (d, J = 16.4 Hz, 1H, CH), 2.06 (s, 3H, CH3), 2.18 (d, J = 16.4 Hz, 1H, CH), 2.33 (d, J = 17.2 Hz, 1H, CH), 2.42 (d, J = 17.2 Hz, 1H, CH), 4.42 (s, 1H, CH), 7.14 (d, J = 8.4 Hz, 2H, ArH), 7.49 (d, J = 8.4 Hz, 2H, ArH), 9.50 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): δ C 18.3, 27.4, 29.2, 32.6, 38.1, 40.8, 50.6, 88.2, 109.1, 119.2, 121.0, 129.3, 131.7, 143.9, 145.2, 149.1, 195.7. IR (KBr): ν 3,306, 3,226, 3,096, 2,960, 2,880, 2,811, 2,197, 1,657, 1,638, 1,496, 1,434, 1,394, 1,365, 1,316, 1,258, 1,198, 1,166, 1,144, 1,129, 1,067, 1,010, 975, 843 cm−1. HRMS (ESI, m/z): Calcd for C19H20BrN2O [M + H]+ 371.0759, found 371.0593.

4-(4-Cyanophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4e: M. p. 251–253 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.91 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.02 (d, J = 16.4 Hz, 1H, CH), 2.08 (s, 3H, CH3), 2.18 (d, J = 16.4 Hz, 1H, CH), 2.35 (d, J = 17.2 Hz, 1H, CH), 2.43 (d, J = 17.2 Hz, 1H, CH), 4.55 (s, 1H, CH), 7.39 (d, J = 8.0 Hz, 2H, ArH), 7.78 (d, J = 8.0 Hz, 2H, ArH), 9.57 (s, 1H, NH). IR (KBr): ν 3,249, 3,158, 3,073, 2,959, 2,931, 2,884, 2,809, 2,749, 2,229, 2,198, 1,656, 1,617, 1,492, 1,433, 1,422, 1,394, 1,380, 1,317, 1,260, 1,146, 1,124, 1,019, 854 cm−1. HRMS (ESI, m/z): Calcd for C20H18N3O [M–H]− 316.145, found 316.1457.

1,4,5,6,7,8-Hexahydro-2,7,7-trimethyl-5-oxo-4-p-tolylquinoline-3-carbonitrile 4f: M. p. 234–236 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.91 (s, 3H, CH3), 1.02 (s, 3H, CH3), 1.99 (d, J = 16.0 Hz, 1H, CH), 2.05 (s, 3H, CH3), 2.17 (d, J = 16.0 Hz, 1H, CH), 2.25 (s, 3H, CH3), 2.32 (d, J = 16.8 Hz, 1H, CH), 2.42 (d, J = 16.8 Hz, 1H, CH), 4.36 (s, 1H, CH), 7.05 (d, J = 8.0 Hz, 2H, ArH), 7.08 (d, J = 8.0 Hz, 2H, ArH), 9.42 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): δ C 18.2, 21.1, 27.4, 29.3, 32.6, 38.0, 40.8, 50.7, 88.8, 109.4, 119.5, 127.3, 129.3, 136.6, 142.0, 144.7, 149.1, 195.8. IR (KBr): ν 3,241, 3,193, 3,079, 2,963, 2,930, 2,881, 2,199, 1,660, 1,607, 1,491, 1,470, 1,435, 1,381, 1,316, 1,258, 1,147, 1,020, 839, 731 cm−1. HRMS (ESI, m/z): Calcd for C20H21N2O [M–H]− 305.1654, found 305.1654.

1,4,5,6,7,8-Hexahydro-4-(2-methoxyphenyl)-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4g: M. p. 255–257 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.98 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.99 (s, 3H, CH3), 1.98 (d, J = 16.0 Hz, 1H, CH), 2.17 (d, J = 16.0 Hz, 1H, CH), 2.34 (d, J = 17.2 Hz, 1H, CH), 2.44 (d, J = 17.2 Hz, 1H, CH), 3.78 (s, 3H, CH3O), 4.84 (s, 1H, CH), 6.84–6.87 (m, 1H, ArH), 6.96 (d, J = 8.0 Hz, 1H, ArH), 7.00 (dd, J = 8.0 Hz, J’ = 1.6 Hz, 1H, ArH), 7.13–7.17 (m, 1H, ArH), 9.33 (s, 1H, NH). IR (KBr): ν 3,299, 3,262, 3,230, 3,097, 2,970, 2,955, 2,938, 2,899, 2,198, 1,657, 1,609, 1,499, 1,460, 1,434, 1,382, 1,316, 1,257, 1,163, 1,147, 1,138, 1,100, 1,014, 764 cm−1. HRMS (ESI, m/z): Calcd for C20H21N2O2 [M–H]− 321.1602, found 321.1614.

4-(2,3-Dichlorophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4g: M. p. >300 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.95 (s, 3H, CH3), 1.03 (s, 3H, CH3), 1.98 (d, J = 16.0 Hz, 1H, CH), 2.04 (s, 3H, CH3), 2.17 (d, J = 16.0 Hz, 1H, CH), 2.35 (d, J = 16.8 Hz, 1H, CH), 2.44 (d, J = 16.8 Hz, 1H, CH), 5.05 (s, 1H, CH), 7.22 (dd, J = 8.0 Hz, J’ = 1.2 Hz, 1H, ArH), 7.32 (t, J = 8.0 Hz, 1H, ArH), 7.48 (dd, J = 8.0 Hz, J’ = 1.2 Hz, 1H, ArH), 9.87 (s, 1H, NH). IR (KBr): ν 3,284, 3,236, 3,104, 2,962, 2,957, 2,914, 2,868, 2,193, 1,650, 1,502, 1,447, 1,421, 1,377, 1,321, 1,305, 1,258, 1,153, 1,137, 1,041, 766, 713 cm−1. HRMS (ESI, m/z): Calcd for C19H17Cl2N2O [M - H]− 359.0718, found 359.0718.

4-(2,4-Dichlorophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4i: M. p. 253–255 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.95 (s, 3H, CH3), 1.02 (s, 3H, CH3), 1.98 (d, J = 16.4 Hz, 1H, CH), 2.03 (s, 3H, CH3), 2.17 (d, J = 16.4 Hz, 1H, CH), 2.34 (d, J = 17.2 Hz, 1H, CH), 2.44 (d, J = 17.2 Hz, 1H, CH), 4.95 (s, 1H, CH), 7.25 (d, J = 8.4 Hz, 1H, ArH), 7.39 (dd, J = 8.4 Hz, J’ = 2.0 Hz, 1H, ArH), 7.53 (d, J = 2.0 Hz, 1H, ArH), 9.55 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): δ C 18.4, 27.5, 29.2, 32.5, 36.4, 41.0, 50.4, 87.3, 108.8, 118.6, 127.4, 129.8, 131.6, 133.3, 133.7, 140.3, 145.1, 149.0, 195.1. IR (KBr): ν 3,185, 3,075, 2,960, 2,936, 2,888, 2,870, 2,810, 2,204, 1,658, 1,604, 1,501, 1,470, 1,435, 1,381, 1,316, 1,259, 1,148, 1,131, 1,100, 1,045, 848, 839 cm−1. HRMS (ESI, m/z): Calcd for C19H17Cl2N2O [M–H]− 359.0718, found 359.0716.

4-(3,4-Dichlorophenyl)-1,4,5,6,7,8-hexahydro-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4j: M. p. 231–233 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.92 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.03 (d, J = 16.0 Hz, 1H, CH), 2.08 (s, 3H, CH3), 2.18 (d, J = 16.0 Hz, 1H, CH), 2.35 (d, J = 16.8 Hz, 1H, CH), 2.42 (d, J = 16.8 Hz, 1H, CH), 4.49 (s, 1H, CH), 7.19 (dd, J = 8.4 Hz, J’ = 2.0 Hz, 1H, CH), 7.39 (d, J = 2.0 Hz, 1H, ArH), 7.58 (d, J = 8.4 Hz, 1H, ArH), 9.56 (s, 1H, NH). 13C NMR (CDCl3, 100 MHz): δ C 18.6, 27.5, 29.1, 32.7, 38.0, 41.2, 50.5, 88.3, 109.3, 118.7, 127.2, 129.5, 130.5, 131.1, 132.7, 144.7, 144.8, 148.1, 195.1. IR (KBr): ν 3,190, 3,079, 2,963, 2,936, 2,885, 2,810, 2,750, 2,360, 2,341, 2,207, 1,659, 1,609, 1,490, 1,437, 1,392, 1,351, 1,319, 1,259, 1,147, 1,129, 1,032, 876, 829 cm−1. HRMS (ESI, m/z): Calcd for C19H17Cl2N2O [M–H]+ 359.0718, found 359.0704.

1,4,5,6,7,8-Hexahydro-4-(3,5-dimethoxyphenyl)-2,7,7-trimethyl-5-oxoquinoline-3-carbonitrile 4k: M. p. 241–243 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 0.96 (s, 3H, CH3), 1.03 (s, 3H, CH3), 2.02–2.06 (m, 4H, CH + CH3), 2.19 (d, J = 16.4 Hz, 1H, CH), 2.34 (d, J = 16.8 Hz, 1H, CH), 2.44 (d, J = 16.8 Hz, 1H, CH), 3.70 (s, 6H, 2CH3O), 4.34 (s, 1H, CH), 6.29 (d, J = 2.0 Hz, 2H, ArH), 6.35 (d, J = 2.0 Hz, 1H, ArH), 9.43 (s, 1H, NH). IR (KBr): ν 3,291, 3,265, 3,233, 3,097, 2,954, 2,840, 2,196, 1,657, 1,610, 1,496, 1,469, 1,431, 1,379, 1,315, 1,257, 1,199, 1,157, 1,065, 858, 709 cm−1. HRMS (ESI, m/z): Calcd for C21H23N2O3 [M - H]+ 351.1709, found 351.1712.

1,4,5,6-Tetrahydro-2-methyl-5,6-dioxo-4-phenylbenzo[h]quinoline-3-carbonitrile 6a: M. p. 256–258 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 4.81 (s, 1H, CH), 7.21–7.25 (m, 1H, ArH), 7.30–7.35 (m, 4H, ArH), 7.78–7.88 (m, 3H, ArH), 8.03–8.05 (m, 1H, ArH), 10.00 (s, 1H, NH). IR (KBr): ν 3,127, 3,043, 2,928, 2,839, 2,360, 2,341, 2,197, 1,678, 1,653, 1,637, 1,592, 1,493, 1,367, 1,344, 1,299, 1,244, 1,206, 1,103, 953, 727, 714 cm−1. HRMS (ESI, m/z): Calcd for C21H13N2O2 [M–H]− 325.0976, found 325.0969.

4-(4-Chlorophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h]quinoline-3-carbonitrile 6b: M. p. 263–265 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 4.84 (s, 1H, CH), 7.35 (d, J = 8.4 Hz, 2H, ArH), 7.37 (d, J = 8.4 Hz, 2H, ArH), 7.79–7.88 (m, 3H, ArH), 8.03–8.05 (m, 1H, ArH), 10.03 (s, 1H, NH). 13C NMR (DMSO-d 6, 100 MHz): δ C 18.3, 38.5, 86.2, 115.1, 119.7, 126.0, 126.5, 129.0, 130.1, 130.8, 132.2, 132.3, 133.8, 135.3, 139.0, 144.0, 147.5, 179.6, 182.4. IR (KBr): ν 3,286, 3,047, 2,985, 2,875, 2,360, 2,341, 2,202, 1,684, 1,650, 1,612, 1,592, 1,490, 1,434, 1,393, 1,364, 1,340, 1,298, 1,252, 1,163, 1,100, 1,087, 1,012, 951 cm−1. HRMS (ESI, m/z): Calcd for C21H12ClN2O2 [M–H]− 359.0588, found 359.0586.

4-(4-Fluorophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h]quinoline-3-carbonitrile 6c: M. p. 273–275 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 4.82 (s, 1H, CH), 7.14 (t, J = 8.8 Hz, 2H, ArH), 7.34–7.38 (m, 2H, ArH), 7.79–7.88 (m, 3H, ArH), 8.03–8.05 (m, 1H, ArH), 10.01 (s, 1H, NH). 13C NMR(DMSO-d 6, 100 MHz): δ C 18.3, 38.3, 86.4, 115.3, 115.8 (d, J F–C = 21.2 Hz), 119.7, 126.0, 126.4, 130.1 (d, J F–C = 8.2 Hz), 130.8, 132.2, 133.8, 135.3, 138.8, 141.3 (d, J F–C = 2.9 Hz), 147.3, 161.7 (d, J F–C = 241.8 Hz), 179.7, 182.4. IR (KBr): ν 3,128, 3,043, 2,929, 2,882, 2,799, 2,357, 2,204, 1,675, 1,652, 1,614, 1,595, 1,504, 1,434, 1,368, 1,344, 1,298, 1,251, 1,219, 1,157, 1,097, 955, 842, 722 cm−1. HRMS (ESI, m/z): Calcd for C21H12FN2O2 [M–H]− 343.0883, found 343.0885.

4-(4-Bromophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h]quinoline-3-carbonitrile 6d: M. p. 267–269 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.20 (s, 3H, CH3), 4.82 (s, 1H, CH), 7.29 (d, J = 8.4 Hz, 2H, ArH), 7.51 (d, J = 8.4 Hz, 2H, ArH), 7.79–7.87 (m, 3H, ArH), 8.02–8.04 (m, 1H, ArH), 10.03 (s, 1H, NH). 13C NMR (DMSO-d 6, 100 MHz): δ C 18.3, 38.6, 86.1, 115.0, 119.7, 120.9, 126.0, 126.4, 130.5, 130.8, 132.0, 132.2, 133.8, 135.3, 139.0, 144.4, 147.5, 179.6, 182.3. IR (KBr): ν 3,234, 3,213, 3,093, 3,062, 2,983, 2,750, 2,359, 2,340, 2,208, 1,678, 1,650, 1,610, 1,595, 1,488, 1,428, 1,339, 1,298, 1,252, 1,069, 1,009, 952, 938, 722 cm−1. HRMS (ESI, m/z): Calcd for C21H12BrN2O2 [M–H]− 403.0081, found 403.0097.

4-(4-Cyanophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h]quinoline-3-carbonitrile 6e: M. p. 267–269 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 4.96 (s, 1H, CH), 7.56 (d, J = 8.4 Hz, 2H, ArH), 7.80–7.86 (m, 5H, ArH), 8.04–8.06 (m, 1H, ArH), 10.09 (s, 1H, NH). 13C NMR(DMSO-d 6, 100 MHz): δ C 18.3, 39.2, 85.7, 110.5, 114.5, 119.1, 119.5, 126.0, 126.5, 129.3, 130.8, 132.1, 133.1, 133.8, 135.3, 139.4, 148.0, 150.0, 179.5, 182.3. IR (KBr): ν 3,300, 3,140, 3,035, 2,910, 2,870, 2,798, 2,420, 2,360, 2,224, 2,201, 1,674, 1,650, 1,614, 1,503, 1,435, 1,344, 1,301, 1,252, 1,159, 1,101, 949, 833, 751, 723 cm−1. HRMS (ESI, m/z): Calcd for C22H12N3O2 [M–H]− 350.093, found 350.0938.

1,4,5,6-Tetrahydro-2-methyl-5,6-dioxo-4-p-tolylbenzo[h]quinoline-3-carbonitrile 6f: M. p. 263–265 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.20 (s, 3H, CH3), 2.24 (s, 3H, CH3), 4.76 (s, 1H, CH), 7.12 (d, J = 8.0 Hz, 2H, ArH), 7.19 (d, J = 8.0 Hz, 2H, ArH), 7.79–7.87 (m, 3H, ArH), 8.02–8.05 (m, 1H, ArH), 9.97 (s, 1H, NH). 13C NMR (DMSO-d 6, 100 MHz): δ C 18.3, 21.1, 38.5, 86.7, 115.7, 119.8, 125.9, 126.4, 128.0, 129.6, 130.7, 132.2, 133.8, 135.3, 136.8, 138.6, 142.2, 147.0, 179.7, 182.4. IR (KBr): ν 3,245, 3,120, 3,031, 2,925, 2,881, 2,359, 2,310, 2,209, 1,678, 1,666, 1,612, 1,487, 1,430, 1,364, 1,339, 1,297, 1,251, 1,208, 1,161, 1,092, 1,050, 950, 721 cm−1. HRMS (ESI, m/z): Calcd for C22H15N2O2 [M–H]− 339.1134, found 339.1141.

1,4,5,6-Tetrahydro-4-(4-methoxyphenyl)-2-methyl-5,6-dioxobenzo[h]quinoline-3-carbonitrile 6g: M. p. 260–262 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 3.71 (s, 3H, CH3O), 4.75 (s, 1H, CH), 6.87 (d, J = 8.4 Hz, 2H, ArH), 7.22 (d, J = 8.4 Hz, 2H, ArH), 7.79–7.88 (m, 3H, ArH), 8.03 (d, J = 7.2 Hz, 1H, ArH), 9.96 (s, 1H, NH). IR (KBr): ν 3,350, 3,085, 2,901, 2,810, 2,359, 2,339, 2,205, 1,675, 1,650, 1,611, 1,595, 1,489, 1,434, 1,343, 1,298, 1,253, 1,176, 1,098, 1,033, 951 cm−1. HRMS (ESI, m/z): Calcd for C22H15N2O3 [M–H]− 355.1083, found 355.1089.

4-(2,3-Dichlorophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h]quino line-3-carbonitrile 6h: M. p. 280–282 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.18 (s, 3H, CH3), 5.46 (s, 1H, CH), 7.29–7.33 (m, 1H, ArH), 7.46 (dd, J = 7.6 Hz, J’ = 1.2 Hz, 1H, ArH), 7.52 (dd, J = 7.6 Hz, J’ = 1.2 Hz, 1H, ArH), 7.80–7.84 (m, 3H, ArH), 8.04–8.07 (m, 1H, ArH), 10.07 (s, 1H, NH). IR (KBr): ν 3,131, 3,042, 2,929, 2,881, 2,800, 2,360, 2,341, 2,205, 1,669, 1,640, 1,614, 1,593, 1,503, 1,474, 1,420, 1,367, 1,346, 1,304, 1,254, 1,158, 1,095, 955, 745 cm−1. HRMS (ESI, m/z): Calcd for C21H11Cl2N2O2 [M - H]− 393.0198, found 393.0196.

4-(2,4-Dichlorophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h] quinoline-3-carbonitrile 6i: M. p. 257–259 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.18 (s, 3H, CH3), 5.35 (s, 1H, CH), 7.36 (dd, J = 8.4 Hz, J’ = 2.0 Hz, 1H, ArH), 7.49 (d, J = 8.4 Hz, 1H, ArH), 7.60 (d, J = 2.0 Hz, 1H, ArH), 7.81–7.84 (m, 3H, ArH), 8.06 (dd, J = 6.4 Hz, J’ = 1.6 Hz, 1H, ArH), 10.04 (s, 1H, NH). 13C NMR (DMSO-d 6, 100 MHz): δ C 18.2, 35.8, 85.3, 114.9, 119.2, 126.0, 126.5, 128.6, 129.0, 130.7, 132.1, 132.7, 132.87, 132.88, 133.9, 135.4, 139.7, 142.0, 147.7, 179.6, 182.2. IR (KBr): ν 3,250, 3,066, 2,927, 2,850, 2,359, 2,340, 2,204, 1,671, 1,650, 1,614, 1,592, 1,497, 1,473, 1,434, 1,344, 1,296, 1,253, 1,158, 1,096, 1,046, 951 846, 723 cm−1. HRMS (ESI, m/z): Calcd for C21H11Cl2N2O2 [M–H]− 393.0198, found 393.0198.

4-(3,4-Dichlorophenyl)-1,4,5,6-tetrahydro-2-methyl-5,6-dioxobenzo[h] quinoline-3-carbonitrile 6j: M. p. 231–233 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 4.90 (s, 1H, CH), 7.35 (dd, J = 8.0 Hz, J’ = 2.0 Hz, 1H, ArH), 7.59 (d, J = 8.0 Hz, 1H, ArH), 7.62 (d, J = 2.0 Hz, 1H, ArH), 7.79–7.86 (m, 3H, ArH), 8.03–8.05 (m, 1H, ArH), 10.05 (s, 1H, NH). IR (KBr): ν 3,140, 3,061, 2,928, 2,796, 2,359, 2,340, 2,203, 1,668, 1,650, 1,614, 1,593, 1,496, 1,474, 1,344, 1,300, 1,252, 1,156, 1,130, 1,096, 1,030, 953 cm−1. HRMS (ESI, m/z): Calcd for C21H11Cl2N2O2 [M–H]− 393.0198, found 393.0199.

1,4,5,6-Tetrahydro-4-(3,5-dimethoxyphenyl)-2-methyl-5,6-dioxobenzo[h] quinoline-3-carbonitrile 6k: M. p. 260–262 °C; 1H NMR (DMSO-d 6, 400 MHz): δ H 2.21 (s, 3H, CH3), 3.71 (s, 6H, 2CH3O), 4.74 (s, 1H, CH), 6.40 (d, J = 2.0 Hz, 1H, ArH), 6.42 (d, J = 2.0 Hz, 2H, ArH), 7.78–7.90 (m, 3H, ArH), 8.03–8.05 (m, 1H, ArH), 9.96 (s, 1H, NH). IR (KBr): ν 3,210, 3,094, 2,927, 2,839, 2,810, 2,420, 2,390, 2,201, 1,667, 1,610, 1,595, 1,500, 1,475, 1,431, 1,346, 1,318, 1,256, 1,198, 1,157, 1,097, 1,058, 923, 817, 743, 720 cm−1. HRMS (ESI, m/z): Calcd for C23H17N2O4 [M–H]− 385.1189, found 385.1181.

Conclusions

In summary, a mild, facile, and environmentally benign method was developed for the synthesis of polysubstituted quinoline and benzo[h]quinoline derivatives in high yields in ionic liquids. The advantages of this procedure include mild reaction conditions, good to high yields, one-pot synthesis, operational simplicity, and being environmentally benign.