Introduction

Lactams, particularly pyrrole derivatives, are important structural motifs found in many natural products, synthetic pharmaceuticals, and molecular materials [1, 2]. Among them, 3-arylaminopyrroline-2-one derivatives have shown biological activity, antimicrobial activity, and electroconvulsive shock (ECS)-induced amnesia reversing activity in mice [1–7].

3-Arylaminopyrroline-2-ones were synthesized via three-component condensation reaction of pyruvic acid derivatives, anilines, and aldehydes, in which sometimes processes and synthesies were preformed for imines or \(\beta ,\gamma \)-unsaturated \(\alpha \)-ketoesters [3, 4, 8]. Vaughan and Tripp synthesized 1,5-diary1-2,3-pyrrolidinediones by the condensation of anilines with pyrrolidine-2,3-diones or furan-2(5\(H)\)-ones [9]. Wu and co-workers reported a convenient preparation of 3-aryl-aminopyrroline-2-ones by the reaction between anilines and \(\beta ,\gamma \)-unsaturated \(\alpha \)-ketoesters in boiling dichloromethane [10]. Recently, the synthesis of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones was reported to take place by condensation reaction between anilines, aldehyde, and ethyl pyruvate using H\(_{2}\)SO\(_{4}\) [11], different thioureas, phosphoric acid analogues [12], or SiO\(_{2}\)-FeCl\(_{3 }\) as catalysts [13]. However, all these methods suffer from long reaction times and the use of toluene, a solvent recognized for its toxicity. Therefore, there is still demand for more efficient synthetic strategies to provide these compounds.

We report here the synthesis of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones via three-component condensation reaction of aldehydes, amines, and ethyl pyruvate under catalyst- and solvent-free conditions (Scheme 1).

Scheme 1
scheme 1

Synthesis of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-one derivatives

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Results and discussion

The reaction of benzaldehyde, 4-methyl aniline, and ethyl pyruvate was studied as a model reaction, and the effects of solvents, catalyst loading, and reaction conditions were evaluated (Scheme 2; Tables 1,  2).

Scheme 2
scheme 2

Preparation of 3-(p-toluidino)-5-phenyl-1-p-tolyl-1H-pyrrol-2(5H)-one

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Table 1 Optimization of the reaction conditions for the synthesis of 3-(p-toluidino)-5-phenyl-1-p-tolyl-1H-pyrrol-2(5H)-one under catalyst-free conditions
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Table 2 Influence of solid silica-supported acids and bases on our solvent-free reaction
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As shown in Table 1, different solvents [n-hexane (bp \(69\,^{\circ }\hbox {C}\)), dichloromethane (bp \(39\,^{\circ }\hbox {C}\)), chloroform (bp \(61\,^{\circ }\hbox {C}\)), and ethanol (bp \(78\,^{\circ }\hbox {C}\))], and solvent-free conditions were studied under catalyst-free conditions. The best conditions were found to be solvent-free at \(80\,^{\circ }\hbox {C}\).

The effect of solid silica-supported acids and bases were investigated (Table 2; Scheme 3). Solid silica-supported bases such as silica-bonded \(N\)-propylpiperazine sodium \(N\)-propionate (1) [14], silica-bonded \(N\)-propylpiperazine (2) [15, 16], silica-bonded \(N\)-propyl morpholine (3) [17], and silica-bonded \(N\)-propyl-triethylenetetramine (4) [18] were examined in the model reaction as catalyst. As shown in Table 2, the catalytic amounts of 0.008 g for catalysts 1,2, and 4; and 0.05 g for 3 at \(100\,^{\circ }\hbox {C}\) gave the corresponding products in the range of 85–93 solvent-free conditions.

Scheme 3
scheme 3

The structures of solid bases and acids used as catalysts

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Solid silica-supported acids such as silica-bonded \(N\)-propyl-triethylenetetramine sulfamic acid (5) [19], silica-bonded \(S\)-sulfonic acid (6) [20], and silica-bonded \(N\)-propyl sulfamic acid (7) [21] were used as catalysts in model reaction. The catalytic amounts of 0.075 g of catalyst 5 and 0.05 g for catalysts 6 and 7 gave the corresponding products in 90, 87, and 85 % yields, respectively, at \(100\,^{\circ }\hbox {C}\) and under solvent-free conditions (Table 2, entries 7–9). The optimum reaction condition is as follows: aldehyde (1 mmol), anilines (2 mmol), ethyl pyruvate (1 mmol), temperature = \(80\,^{\circ }\hbox {C}\), no catalyst, and solvent-free.

As shown in Table 3, this three-component condensation reaction proceeded with different substituted aromatic aldehydes and aniline derivatives under the optimized condition. Aromatic aldehydes containing electron-donating groups or electron-withdrawing groups gave corresponding products in high yields (Table 3). Butyraldehyde, the only aliphatic aldehyde tested, gives desired product in 90 % yield (Table 3, entry 12).

Table 3 Synthesis results using optimized reaction conditions
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3-Pyridine carbaldehyde, the only heterocyclic aldehyde tested, also gave the required product in 90 % yield (Table 3, entry 13). As for anilines, those bearing electron-donating and electron-withdrawing groups gave products with high and lower yields, respectively (Table 3).

We would like to mention that when we used 4-hydroxy-3-nitro-benzyl oxime instead of the corresponding aldehyde and treated with ethyl pyruvate and 4-methoxy-aniline, the expected product 5-(hydroxyl-3-nitrophenyl)-1-(4-methoxyphenyl)-3-(4-methox-yphenylamino)-1,5-dihydro-pyrrol-2- one was obtained after 25 min in 40 % yield. This confirms that aldehydes are the better substrates than the corresponding oximes in such a three-component condensation reactions.

In conclusion, we present, in this study, the synthesis of 1,5-diaryl-3-(arylamino)-1H-pyrrol-2(5H)-ones that were prepared by a three-component condensation reaction of aldehydes, aromatic amines, and ethyl pyruvate under catalyst-free and solvent-free conditions in good-to-high yields. This simple and green procedure, under catalyst-free and solvent-free conditions and much shorter reaction times, represents the advantages of this method.

Experimental

General

Chemicals were purchased from Fluka, Merck and Aldrich Chemical Companies and used as received. \(^{1}\)H-NMR spectra were recorded on a Bruker Ultrashield (400 MHz) using CDCl\(_{3}\) as deuterated solvent and with tetramethylsilane (TMS) as internal standard. Mass spectra were recorded on a FINNIGAN-MAT 8430 mass spectrometer operating at 70 eV. Melting points were determined in open capillary tubes in a Barnstead Electrothermal 9100 BZ circulating oil melting point apparatus and uncorrected. Reactions were monitored by TLC using silica gel Poly Gram SILG/UV254 plates. All the products were characterized by IR, NMR, Mass spectra, and known compounds and compared to those reported in the literature [10–13]. Solid silica-supported bases such as silica-bonded \(N\)-propylpiperazine sodium \(N\)-propionate (1) [14], silica-bonded \(N\)-propylpiperazine (2) [15, 16], silica-bonded \(N\)-propylmorpholine (3) [17], and silica-bonded \(N\)-propyl-triethylenetetramine (4) [18]; and solid silica-supported acids such as silica-bonded \(N\)-propyl-triethylenetetramine sulfamic acid (5) [19], silica-bonded \(S\)-sulfonic acid (6) [20], and silica-bonded \(N\)-propyl sulfamic acid (7) [21], were prepared according to our reported procedures.

General procedure for the synthesis of 1,5-diaryl-3-(arylamino)-1H -pyrrol-2(5H)-ones

A mixture of aldehyde (1 mmol), aromatic amine (2 mmol), and ethyl pyruvate (1 mmol) was heated with stirring in an oil bath at \(80\,^{\circ }\hbox {C}\) under catalyst-free and solvent-free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the crude products were purified by recrystallization from ethanol (95 %).

1,5-Diphenyl-3-phenylamino)-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 1)

White solid; 0.29 g, 90 % yield; mp \(227{-}229\,^{\circ }\hbox {C}\). IR (KBr): 3,330 (N–H), 1,679 (cm\(^{-1}\)) (N–C=O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 5.72 (1H, d, \(J =\) 2.4 Hz, CH), 6.12 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.69 (1H, s, NH), 6.97 (1H, t, \(J =\) 8.4 Hz, Ar), 7.09–7.13 (3H, m, Ar), 7.23–7.28 (3H, m, Ar), 7.30–7.36 (6H, m, Ar), 7.56–7.58 (2H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 64.2, 108.3, 116.7, 121.3, 121.6, 124.9, 126.7, 128.9, 129.0, 129.4, 131.9, 137.3, 137.5, 141.3, 167.3. Anal. Calcd for C\(_{22}\)H\(_{18}\)N\(_{2}\)O: C, 80.96; H, 5.56; N, 8.58; found: C, 80.69; H, 5.62; N, 8.36.

MS (EI, 70 eV): m/z (%) \(=\) 326 (M\(^{+}\), base peak), 297 (28.7), 206 (97.5), 77 (85).

1-(4-Methoxyphenyl)-3-(4-methoxyphenyl-amino)-5-(3-chlorophenyl)-1H-pyrrol-2(5H)-one (Table 3, entry 2)

White cream solid; 0.41 g, 93 % yield; mp \(192-194\,^{\circ }\hbox {C}\), (Lit.: [13] \(164{-}166\,^{\circ }\hbox {C}\)). IR (KBr): 3,313 (N–H), 1,672 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 3.78 (3H, s, OCH\(_{3})\), 3.81 (3H, s, OCH\(_{3})\), 5.57 (1H, d, \(J =\) 2.4 Hz, CH), 5.92 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.49 (1H, s, NH), 6.85-6.90 (4H, m, Ar), 7.05–7.10 (3H, m, Ar), 7.21–7.23 (3H, m, Ar), 7.36–7.39 (2H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 55.4, 55.6, 64.2, 105.3, 114.1, 114.7, 118.6, 123.8, 125.1, 127.1, 128.4, 129.9, 130.2, 133.3, 134.6, 134.7, 140.0, 154.6, 157.1, 167.1.

MS (EI, 70 eV): m/z (%) \(=\) 422 (M\(^{+2}\), 22), 420 (M\(^{+}\), 54), 298 (21), 270 (base peak), 259 (22), 122 (27), 92 (20), 77 (25).

1-(4-Methoxyphenyl)-3-(4-methoxyphenyl-amino)-5-(4-chlorophenyl)-1H-pyrrol-2(5H)-one (Table 3, entry 3)

White cream solid; 0.29 g, 67 % yield; mp \(195-197\,^{\circ }\hbox {C}\), (Lit.: [13] \(153{-}155\,^{\circ }\hbox {C}\)). IR (KBr): 3,313 (N–H), 1,674 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 3.78 (3H, s, OCH\(_{3})\), 3.81 (3H, s, OCH\(_{3})\), 5.57 (1H, d, \(J =\) 2.4 Hz, CH), 5.92 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.49 (1H, s, NH), 6.84-6.91 (4H, m, Ar), 7.05-7.07 (2H, m, Ar), 7.14–7.17 (2H, m, Ar), 7.25–7.28 (2H, m, Ar), 7.34–7.36 (2H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \)(ppm): 55.4, 55.6, 64.1, 105.5, 114.3, 114.7, 118.6, 123.9, 128.4, 129.1, 129.9, 133.3, 133.9, 134.7, 136.3, 154.5, 157.1, 167.0.

MS (EI, 70 eV): m/z (%) \(=\) 422 (M\(^{+2}\), 0.8), 420 (M\(^{+}\), 1.6), 264 (8), 122 (7.1), 97 (14.2), 69 (25.4), 57 (base peak).

1-(4-Methoxyphenyl)-3-(4-methoxyphenyl-amino)-5-(4-bromophenyl)-1H-pyrrol-2(5H)-one (Table 3, entry 4)

White solid; 0.16 g, 35 % yield; mp \(213{-}215^{\circ }\hbox {C}\). IR (KBr): 3,309 (N–H), 1,672 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 3.78 (3H, s, OCH\(_{3})\), 3.81 (3H, s, OCH\(_{3})\), 5.56 (1H, d, \(J =\) 2.4 Hz, CH), 5.92 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.47 (1H, s, NH), 6.84–6.90 (4H, m, Ar), 7.02–7.10 (4H, m, Ar), 7.34–7.36 (2H, m, Ar), 7.41–7.50 (3H, m, Ar). \(^{13}\)C NMR (100 MHz; CDCl\(_{3}) \quad \delta \) (ppm): 55.4, 55.6, 64.1, 105.4, 114.3, 114.7, 118.6, 121.9, 123.9, 128.7, 129.9, 132.1, 133.3, 134.7, 136.9, 154.6, 157.1, 167.0. Anal. Calcd for C\(_{24}\)H\(_{21}\)BrN\(_{2}\)O\(_{3}\): C, 61.95; H, 4.55; Br, 17.17; N, 6.02; found: C, 61.73; H, 4.61; N, 5.84.

MS (EI, 70 eV): m/z (%) \(=\) 466 (M\(^{+}\)+2, 36.8), 464 (M\(^{+}\), 37.5), 323 (base peak), 77 (49.3).

5-Phenyl-1-p-tolyl-3-p-tolylamino-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 5)

White cream solid; 0.32 g, 91 % yield; mp \(215{-}217\,^{\circ }\hbox {C}\), (Lit.: [10] \(215{-}217\,^{\circ }\hbox {C}\)). IR (KBr): 3,311 (N–H), 1,675 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 2.28 (3H, s, CH\(_{3})\), 2.32 (3H, s, CH\(_{3})\), 5.66 (1H, d, \(J =\) 2.8 Hz, CH), 6.04 (1H, d, \(J =\) 2.8 Hz, \(=\) CH), 6.59 (1H, s, NH), 7.00 (2H, d, \(J =\) 8.4 Hz, Ar), 7.09–7.13 (4H, m, Ar), 7.22–7.7.32 (5H, m, Ar), 7.44 (2H, d, \(J =\) 7.6 Hz, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \)(ppm): 20.7, 20.9, 64.4, 107.4, 116.8, 121.7, 126.8, 128.1, 128.9, 129.5, 129.9, 130.7, 132.4, 134.7, 134.7, 137.7, 138.9, 167.3.

MS (EI, 70 eV): m/z (%) \(=\) 354 (M\(^{+}\), 3), 281 (8), 207 (16), 109 (16.5), 91 (69), 69 (56), 57 (92), 55 (base peak).

5-(4-Methoxy-phenyl)-1-p-tolyl-3-p-tolylamino-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 6)

White cream solid; 0.25 g, 65 % yield; mp \(214{-}216\,^{\circ }\hbox {C}\). IR (KBr): 3,313 (N–H), 1,672 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 2.29 (3H, s, CH\(_{3})\), 2.32 (3H, s, CH\(_{3})\), 3.77 (3H, s, OCH\(_{3})\), 5.61 (1H, d, \(J =\) 2.4 Hz, CH), 6.02 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.58 (1H, s, NH), 6.81–6.84 (2H, m, Ar), 6.99–7.02 (2H, m, Ar), 7.10–7.16 (6H, m, Ar), 7.37–7.41 (2H, m, Ar). \(^{13}\)C NMR (100 MHz; CDCl\(_{3}) \quad \delta \) (ppm): 20.7, 20.9, 55.2, 63.9, 107.6, 114.3, 116.8, 122.0, 128.1, 129.4, 129.5, 129.9, 130.6, 132.3, 134.7, 134.7, 138.9, 159.4, 167.2. Anal. Calcd for C\(_{25}\)H\(_{24}\)N\(_{2}\)O\(_{2}\): C, 78.10; H, 6.29; N, 7.29; found: C, 77.84; H, 6.32; N, 7.10.

MS (EI, 70 eV): m/z (%) \(=\) 384 (M\(^{+}\), 25.0), 291 (23.3), 250 (75.0), 91 (98.3), 77 (56.7), 57 (base peak).

5-(4-Nitro-phenyl)-1-p-tolyl-3-p-tolylamino-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 7)

Yellow solid; 0.28 g, 70 % yield; mp \(231{-}233\,^{\circ }\hbox {C}\). IR (KBr): 3,313 (N–H), 1,682 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 2.29 (3H, s, CH\(_{3})\), 2.32 (3H, s, CH\(_{3})\), 5.78 (1H, d, \(J =\) 2.4 Hz, CH), 5.99 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.63 (1H, s, NH), 7.00 (2H, t, \(J =\) 8.4 Hz, Ar), 7.12–7.15 (4H, m, Ar), 7.31–7.42 (4H, m, Ar), 8.16 (2H, dd, J\(_{1} =\) 6.8, J\(_{2} =\) 1.6 Hz, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 20.7, 20.9, 63.5, 105.3, 117.1, 121.6, 124.3, 127.7, 129.8, 129.9, 131.3, 133.2, 134.1, 135.3, 138.4, 145.5, 147.7, 166.9. Anal. Calcd for C\(_{24}\)H\(_{21}\)N\(_{3}\)O\(_{3}\): C, 72.16; H, 5.30; N, 10.52; found: C, 71.89; H, 5.34; N, 10.34.

MS (EI, 70 eV): m/z (%) \(=\) 399 (M\(^{+}\), 2.2), 314 (15.5), 295 (26.7), 91 (86.7), 77 (55.6), 55 (base peak).

1-(3-Chloro-phenyl)-3-(3-chloro-phenylamino)-5-phenyl-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 8)

White cream solid; 0.36 g, 90 % yield; mp \(203{-}205\,^{\circ }\hbox {C}\), (Lit.: [10] \(207{-}209\,^{\circ }\hbox {C}\)). IR (KBr): 3,320 (N–H), 1,679 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 5.69 (1H, d, \(J =\) 2.4 Hz, CH), 6.14 (1H, d, \(J =\) 2.8 Hz, \(=\) CH), 6.72 (1H, s, NH), 6.94–6.97 (2H, m, Ar), 7.07–7.10 (2H, m, Ar), 7.20–7.26 (3H, m, Ar), 7.31–7.41 (5H, m, Ar), 7.73 (1H, t, \(J =\) 2.2 Hz, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 64.2, 109.5, 115.0, 116.4, 119.1, 121.4, 121.4, 125.0, 126.6, 128.5, 129.3, 129.9, 130.4, 131.4, 134.7, 135.1, 136.6, 138.3, 142.3, 167.

MS (EI, 70 eV): m/z (%) \(=\) 396 (M\(^{+2}\), 50), 394 (M\(^{+}\), 75), 268 (87), 240 (base peak), 229 (80), 204 (34), 75 (29).

1-(4-Chloro-phenyl)-3-(4-chloro-phenylamino)-5-phenyl-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 9)

White solid; 0.37 g, 93 % yield; mp \(208{-}210\,^{\circ }\hbox {C}\), (Lit.: [10] \(217{-}219\,^{\circ }\hbox {C}\)). IR (KBr): 3328 (N–H), 1,672 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 5.67 (1H, d, \(J =\) 2.8 Hz, CH), 6.08 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.68 (1H, s, NH), 7.00–7.04 (2H, m, Ar), 7.19–7.22 (2H, m, Ar), 7.28–7.37 (7H, m, Ar), 7.51–7.55 (2H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \)(ppm): 64.2, 108.6, 117.9, 122.5, 126.2, 126.7, 128.5, 129.1, 129.2, 129.4, 130.3, 131.8, 135.7, 136.8, 139.7, 167.0.

MS (EI, 70 eV): m/z (%) \(=\) 396 (M\(^{+2}\), 31.5), 394 (M\(^{+}\), 49), 268 (49), 240 (base peak), 229 (40), 204 (24), 75 (22.5).

1-(4-Bromo-phenyl)-3-(4-bromo-phenylamino)-5-phenyl-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 10)

Cream solid; 0.46 g, 95 % yield; mp \(226{-}228\,^{\circ }\hbox {C}\), (Lit.: [12]). IR (KBr): 3,327 (N–H), 1,672 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 5.66 (1H, d, \(J =\) 2.4 Hz, CH), 6.08 (1H, d, \(J =\) 2.4 Hz, CH\(=\)), 6.68 (1H, s, NH), 6.95–7.01 (2H, m, Ar), 7.19–7.22 (2H, m, Ar), 7.30–7.35 (3H, m, Ar), 7.39–7.43 (4H, m, Ar), 7.46–7.49 (2H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 64.1, 108.9, 113.5, 118.0, 118.3, 122.8, 126.6, 128.5, 129.2, 131.7, 132.0, 132.3, 136.2, 136.8, 140.2, 167.0.

MS (EI, 70 eV): m/z (%) \(=\) 486 (M\(^{+4}\), 19), 484 (M\(^{+2}\), 39), 480 (M\(^{+}\), 20), 314 (43), 312 (45), 286 (88), 284 (base peak), 204 (79), 76 (28).

5-(4-Methoxy-phenyl)-1-(3-nitrophenyl)-3-(3-nitrophenyl-amino)-1,5-dihydro-1H-pyrrol-2(5H)-one (Table 3, entry 11)

Yellow solid; 0.20 g, 45 % yield; mp \(184{-}186\,^{\circ }\hbox {C}\). IR (KBr): 3,375 (N–H), 1,697 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 3.78 (3H, s, OCH\(_{3})\), 5.80 (1H, s, CH), 6.30 (1H, s, \(=\) CH), 6.87 (2H, d, \(J =\) 8.4 Hz, Ar), 7.05 (1H, s, NH), 7.20 (2H, d, \(J =\) 8.4 Hz, Ar), 7.38–7.40 (1H, m, Ar), 7.46–7.51 (2H, m, Ar), 7.84 (1H, d, \(J =\) 7.6 Hz, Ar), 7.96–8.03 (3H, m, Ar), 8.49 (1H, s, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 55.3, 63.8, 110.4, 111.1, 114.9, 115.8, 116.1, 119.5, 122.7, 126.6, 127.1, 128.1, 129.8, 130.2, 130.9, 138.0, 142.1, 148.5, 149.2, 160.0, 166.9. Anal. Calcd for C\(_{23}\)H\(_{18}\)N\(_{4}\)O\(_{6}\): C, 61.88; H, 4.06; N, 12.55; found: C, 61.69; H, 4.13; N, 12.39.

MS (EI, 70 eV): m/z (%) \(=\) 446 (M\(^{+}\), 8.3), 382 (37.2), 262 (33.3), 234 (base peak), 77 (88.9), 57 (95.5).

1-(4-Methoxyphenyl)-3-(4-methoxyphenylamino)-5-propyl-1,5-dihydro-pyrrole-2(5H)-one (Table 3, entry 12)

Pale yellow solid; 0.32 g, 90 % yield; mp \(201{-}203\,^{\circ }\hbox {C}\). IR (KBr): 3,311 (N–H), 1,673 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 0.87 (3H, t, \(J =\) 7.2 Hz, CH\(_{3})\), 1.26–1.46 (4H, m, 2 \(\times \) CH\(_{2})\), 3.83 (3H, s, OCH\(_{3})\), 3.86 (3H, s, OCH\(_{3})\), 4.65–4.68 (1H, m, CH), 5.98 (1H, d, \(J =\) 2.4 Hz, \(=\) CH), 6.40 (1H, s, NH), 6.90–6.94 (2H, m, Ar), 6.97–7.09 (4H, m, Ar), 7.37–7.41 (2H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 14.1, 17.4, 34.1, 55.5, 55.6, 60.1, 104.4, 114.4, 114.7, 118.4, 124.8, 129.7, 133.9, 135.2, 154.3, 157.3, 166.3. Anal. Calcd for C\(_{21}\)H\(_{24}\)N\(_{2}\)O\(_{3}\): C, 71.57; H, 6.86; N, 7.95; found: C, 71.38; H, 6.91; N, 7.79.

MS (EI, 70 eV): m/z (%) \(=\) 352 (M\(^{+}\), 33.6), 309 (59.1), 202 (45.5), 77 (63.6), 69 (base peak), 55 (89.1).

1-(4-Methoxyphenyl)-3-(4-methoxyphenylamino)-5-pyridin-3-yl-1,5-dihydro-pyrrole-2(5H)-one (Table 3, entry 13)

Cream solid; 0.35 g, 90 % yield; mp \(204{-}206\,^{\circ }\hbox {C}\). IR (KBr): 3,310 (N–H), 1,665 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 3.77 (3H, s, OCH\(_{3})\), 3.81 (3H, s, OCH\(_{3})\), 5.68 (1H, s, CH), 5.93 (1H, s, \(=\)CH), 6.53 (1H, s, NH), 6.85–6.91 (4H, m, Ar), 7.07 (2H, d, \(J =\) 8.4 Hz, Ar), 7.29–7.35 (3H, m, Ar), 7.59 (1H, d, \(J =\) 8.0 Hz, Ar), 8.54 (1H, d, \(J =\) 4.4 Hz, Ar), 8.59 (1H, s, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 55.4, 55.6, 62.2, 104.6, 114.4, 114.8, 118.7, 124.1, 129.5, 133.8, 133.8, 134.5, 134.7, 148.6, 149.4, 154.7, 157.3, 166.9. Anal. Calcd for C\(_{23}\)H\(_{21}\)N\(_{3}\)O\(_{3}\): C, 71.30; H, 5.46; N, 10.85; found: C, 71.12; H, 5.51; N, 10.67.

MS (EI, 70 eV): m/z (%) \(=\) 387 (M\(^{+}\), 10.0), 323 (7.7), 237 (24.6), 77 (35.4), 69 (70.8), 57 (base peak).

1-(3,4-Dimethylphenyl)-3-(3,4-dimethylphenylamino)-5-phenyl-1,5-dihydro-pyrrole-2(5H)-one (Table 3, entry 14)

White solid; 0.27 g, 70 % yield; mp \(226-228\,^{\circ }\hbox {C}\); (Lit.: [13] \(220{-}222\,^{\circ }\hbox {C}\)). IR (KBr): 3,317 (N–H), 1,675 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 2.18 (3H, s, CH\(_{3})\), 2.22 (6H, s, 2 \(\times \) CH\(_{3})\), 2.29 (3H, s, CH\(_{3})\), 5.64 (1H, d, \(J =\) 2.8 Hz, CH), 6.03 (1H, d, \(J =\) 2.8 Hz, \(=\)CH), 6.54 (1H, s, NH), 6.84–6.89 (2H, m, Ar), 7.02–7.09 (2H, m, Ar), 7.13–7.16 (1H, m, Ar), 7.20–7.28 (3H, m, Ar), 7.30–7.38 (3H, m, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 19.0, 19.2, 20.1, 64.4, 107.2, 114.1, 118.3, 119.4, 123.4, 126.9, 128.1, 128.9, 129.4, 129.9, 130.3, 132.4, 133.6, 134.9, 137.2, 137.6, 137.8, 139.3, 167.3.

MS (EI, 70 eV): m/z (%) \(=\) 382 (M\(^{+}\), 30), 262 (31), 234 (base peak), 222 (29), 105 (43), 77 (72).

1-(3,4-Dimethylphenyl)-3-(3,4-dimethylphenylamino)-5-(4-methoxyphenyl)-1,5-dihydro-pyrrole-2(5H)-one (Table 3, entry 15)

White solid; 0.28 g, 68 % yield; mp \(212{-}214\,^{\circ }\hbox {C}\). IR (KBr): 3,317 (N–H), 1,651 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 2.19 (3H, s, CH\(_{3})\), 2.23 (6H, s, 2 \(\times \) CH\(_{3})\), 2.26 (3H, s, CH\(_{3})\), 3.77 (3H, s, CH\(_{3})\), 5.60 (1H, d, \(J =\) 2.8 Hz, CH), 6.01 (1H, d, \(J =\) 2.8 Hz, \(=\)CH), 6.55 (1H, s, NH), 6.81–6.90 (4H, m, Ar), 7.03–7.08 (2H, m, Ar), 7.12–7.17 (3H, m, Ar), 7.35 (1H, d, \(J =\) 2.0 Hz, Ar). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 19.0, 19.3, 20.1, 55.2, 63.9, 107.4, 114.1, 114.3, 118.3, 119.7, 123.7, 128.2, 129.3, 129.5, 129.9, 130.3, 132.3, 133.6, 134.8, 137.1, 137.6, 139.3, 159.3, 167.2. Anal. Calcd for C\(_{27}\)H\(_{28}\)N\(_{2}\)O\(_{2}\): C, 78.61; H, 6.84; N, 6.79; found C, 78.39 H, 6.90; N, 6.62.

MS (EI, 70 eV): m/z (%) \(=\) 412 (M\(^{+}\), 25.8), 292 (30.8), 264 (base peak), 77 (40.4).

5-(4-hydroxyl-3-nitrophenyl)-1-(4-methoxyphenyl)-3-(4-methoxyphenylamino)-1,5-dihydro-pyrrol-2-one

Orange solid; 0.18 g, 40 % yield; mp \(196{-}202\,^{\circ }\hbox {C}\). IR (KBr): 3,310 (OH), 3,304 (N–H), 1,683 (cm\(^{-1})\) (N–C \(=\) O). \(^{1}\)H NMR (400 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 3.78 (3H, s, OCH\(_{3})\), 3.81 (3H, s, OCH\(_{3})\), 5.61 (1H, s, CH), 5.90 (1H, s, \(=\)CH), 6.52 (1H, s, NH), 6.85–6.91 (4H, m, Ar), 7.03–7.10 (3H, m, Ar), 7.29-7.39 (3H, m, Ar), 8.00 (1H, s, Ar), 10.57 (1H, s, OH). \(^{13}\)C NMR (100 MHz, CDCl\(_{3}) \quad \delta \) (ppm): 55.4, 55.6, 63.5, 114.5, 114.8, 118.8, 121.0, 123.8, 124.1, 124.3, 130.4, 135.8, 155.0, 157.7. Anal. Calcd for C\(_{24}\)H\(_{21}\)N\(_{3}\)O\(_{6}\): C, 64.42; H, 4.73; N, 9.39; found C, 64.12; H, 4.77; N, 9.12.

MS (EI, 70 eV): m/z (%) \(=\) 447 (M\(^{+}\), 1.1), 384 (8.4), 250 (23.2), 147 (17.9), 119 (40.0), 105 (13.2), 91 (37.9), 70 (53.7), 57 (72.6), 55 (base peak).