774
S. Rybka et al.
Arch. Pharm. Chem. Life Sci. 2014, 347, 768–776
calcd. for C16H19N3O2Cl2 (356.25): C, 53.94; H, 5.38; N, 11.80;
Found: C, 53.97; H, 5.42; N, 11.82.
N-[{4-(4-Fluorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-
2,5-dione (18)
White solid. Yield: 74%; m.p. 146–148°C; Rf ¼ 0.44 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.73–2.77 (m, 4H, CH2, imide, 4H, piperazine),
3.05–3.08 (m, 4H, piperazine), 4.52 (s, 2H, CH2), 6.82–6.86 (m, 2H,
ArH), 6.91–6.95 (m, 2H, ArH); 19F NMR (282 MHz, CDCl3) d:
ꢂ124.18 (s, 1F); ESI-MS: 292.27 (C15H18N3O2 F [MþH]þ). Anal. calcd.
for C15H18N3O2F (291.32): C, 61.84; H, 6.23; N, 14.42; Found: C,
61.80; H, 6.20; N, 14.40.
N-[{4-(3-Trifluoromethylphenyl)-piperazin-1-yl}-methyl]-3-
methylpyrrolidine-2,5-dione (13)
White solid. Yield: 64%; m.p. 103–105°C; Rf ¼ 0.50 (S1); 1H NMR
(300 MHz, CDCl3) d: 1.35 (d, 3H, CH3, J ¼ 2.05 Hz), 2.32 (d, 1H,
imide, J ¼ 13.33 Hz), 2.73–2.76 (m, 4H, piperazine), 2.96 (d, 2H,
imide, J ¼ 8.97 Hz), 3.17 (t, 4H, piperazine, J ¼ 5.13 Hz), 4.51 (s, 2H,
CH2), 7.00–7.07 (m, 3H, ArH), 7.29–7.35 (m, 1H, ArH); 13C NMR
(75 MHz, CDCl3) d: 17.03, 34.73, 36.32, 48.78, 50.44, 59.74, 112.37,
116.09, 118.95, 129.54, 131.20, 151.28, 177.28, 181.53; 19F NMR
(282 MHz, CDCl3) d: ꢂ62.78 (s, 3F); ESI-MS: 356.48 (C17H20N3O2F3
[MþH]þ). Anal. calcd. for C17H20N3O2F3 (355.35): C, 57.46; H, 5.67;
N, 11.82; Found: C, 57.48; H, 5.68; N, 11.86.
N-[{4-(2-Chlorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-
2,5-dione (19)
White solid. Yield: 51%; m.p. 68–70°C; Rf ¼ 0.44 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.76 (s, 4H, CH2, imide), 2.78 (brs, 4H,
piperazine), 3.01 (brs, 4H, piperazine), 4.52 (s, 2H, CH2), 6.93 (m,
2H, ArH), 7.18 (d, 1H, ArH, J ¼ 1.54 Hz), 7.32 (d, 1H, ArH,
J ¼ 1.54 Hz); 13C NMR (75 MHz, CDCl3) d: 28.17, 50.84, 51.16, 59.93,
120.36, 123.79, 127.59, 128.65, 130.63, 149.09 178.23; ESI-MS:
308.29 (C15H18N3O2Cl [MþH]þ). Anal. calcd. for C15H18N3O2Cl
(307.78): C, 58.54; H, 5.89; N, 13.65; Found: C, 58.50; H, 5.85; N,
13.65.
N-[{4-(2-Methylphenyl)-piperazin-1-yl}-methyl]-3-
methylpyrrolidine-2,5-dione (14)
White solid. Yield: 43%; m.p. 92–94°C; Rf ¼ 0.47 (S1); 1H NMR
(300 MHz, CDCl3) d: 1.35 (d, 3H, CH3, J ¼ 2.05 Hz), 2.26 (s, 3H, CH3)
2.35 (d, 1H, imide, J ¼ 13.33 Hz), 2.71–2.74 (m, 4H, piperazine),
2.87 (m, 4H, piperazine), 3.00 (d, 2H, imide, J ¼ 9.0 Hz), 4.51 (s, 2H,
CH2), 6.94–7.01 (m, 2H, ArH), 7.13–7.17 (m, 2H, ArH); ESI-MS:
302.30 (C17H23N3O2 [MþH]þ). Anal. calcd. for C17H23N3O2 (301.38):
C, 67.75; H, 7.69; N, 13.94; Found: C, 67.69; H, 7.67; N, 13.90.
N-[{4-(3-Chlorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-
2,5-dione (20)
White solid. Yield: 71%; m.p. 98–100°C; Rf ¼ 0.53 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.72–2.75 (m, 4H, CH2, imide, 4H, piperazine),
3.13–3.17 (m, 4H, piperazine), 4.51 (s, 2H, CH2), 6.75–6.84 (m, 3H,
ArH), 7.11–7.17 (m, 1H, ArH); ESI-MS: 308.29 (C15H18N3O2Cl
[MþH]þ). Anal. calcd. for C15H18N3O2Cl (307.78): C, 58.54; H, 5.89;
N, 13.65; Found: C, 58.50; H, 5.86; N, 13.63.
N-[{4-(3-Methylphenyl)-piperazin-1-yl}-methyl]-3-
methylpyrrolidine-2,5-dione (15)
White solid. Yield: 78%; m.p. 90–92°C; Rf ¼ 0.44 (S1); 1H NMR
(300 MHz, CDCl3) d: 1.35 (d, 3H, CH3, J ¼ 2.31 Hz), 2.30 (s, 3H, CH3),
2.32 (d, 1H, imide, J ¼ 13.33 Hz), 2.72–2.75 (m, 4H, piperazine),
2.95 (d, 2H, imide, J ¼ 8.98 Hz), 3.12–3.15 (m, 4H, piperazine), 4.51
(s, 2H, CH2), 6.69–6.71 (m, 3H, ArH), 7.13–7.15 (m, 1H, ArH); 13C
NMR (75 MHz, CDCl3) d: 17.01, 21.74, 34.72, 36.33, 49.38, 50.66,
59.80, 113.48, 117.16, 120.91, 128.94, 138.81, 151.27, 177.35,
181.58; ESI-MS: 302.37 (C17H23N3O2 [MþH]þ). Anal. calcd. for
N-[{4-(4-Chlorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-
2,5-dione (21)
White solid. Yield: 77%; m.p. 175–177°C; Rf ¼ 0.46 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.72–2.75 (m, 4H, CH2, imide, 4H, piperazine),
3.10 (t, 4H, piperazine, J ¼ 5.13 Hz), 4.51 (s, 2H, CH2), 6.82–6.85 (m,
2H, ArH), 7.17–7.20 (m, 2H, ArH); ESI-MS: 308.22 (C15H17N3O2Cl
[MþH]þ). Anal. calcd. for C15H17N3O2Cl (307.78): C, 58.54; H, 5.89;
N, 13.65; Found: C, 58.57; H, 5.93; N, 13.69.
C17H23N3O2 (301.38): C, 67.75; H, 7.69; N, 13.94; Found: C, 67.78;
H, 7.71; N, 13.95.
N-[4-(Phenylpiperazin-1-yl)-methyl]-pyrrolidine-2,5-dione
(16)
N-[{4-(2,3-Dichlorophenyl)-piperazin-1-yl}-methyl]-
White solid. Yield: 77%; m.p. 140–142°C; Rf ¼ 0.47 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.74 (s, 4H, CH2, imide), 2.75 (t, 4H, piperazine,
J ¼ 5.13 Hz), 3.13 (t, 4H, piperazine, J ¼ 5.13 Hz), 4.52 (s, 2H, CH2),
6.82–6.90 (m, 3H, ArH), 7.22–7.27 (m, 2H, ArH); 13C NMR (75 MHz,
CDCl3) d: 28.12, 49.30, 50.66, 59.84, 116.36, 119.99, 129.11, 151.20,
178.1; ESI-MS: 274.32 (C15H19N3O2 [MþH]þ). Anal. calcd. for
C15H19N3O2 (273.33): C, 65.91; H, 7.01; N, 15.37. Found: C, 65.96;
H, 7.03; N, 15.37.
pyrrolidine-2,5-dione (22)
White solid. Yield: 67%; m.p. 143–145°C; Rf ¼ 0.52 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.76–2.79 (m, 4H, CH2, imide, 4H, piperazine)
2.99 (brs, 4H, piperazine), 4.52 (s, 2H, CH2), 6.91 (d, 1H, ArH,
J ¼ 3.06 Hz), 7.12–7.15 (m, 2H, ArH); ESI-MS: 342.26
(C15H17N3O2Cl2 [MþH]þ). Anal. calcd. for C15H17N3O2Cl2
(342.22): C, 52.64; H, 5.01; N, 12.28; Found: C, 52.62; H, 4.98;
N, 12.24.
N-[{4-(2-Fluorophenyl)-piperazin-1-yl}-methyl]-pyrrolidine-
N-[{4-(3,4-Dichlorophenyl)-piperazin-1-yl}-methyl]-
2,5-dione (17)
White solid. Yield: 78%; m.p. 148–150°C; Rf ¼ 0.47 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.75 (s, 4H, CH2, imide), 2.76 (t, 4H, piperazine,
J ¼ 5.13 Hz), 3.04 (t, 4H, piperazine, J ¼ 5.13 Hz), 4.52 (s, 2H, CH2),
6.90–6.97 (m, 3H, ArH), 7.02–7.05 (m, 1H, ArH); 19F NMR (282 MHz,
CDCl3) d: ꢂ123.06 (s, 1F); ESI-MS: 292.27 (C15H18N3O2 F [MþH]þ).
Anal. calcd. for C15H18N3O2F (291.32): C, 61.84; H, 6.23; N, 14.42;
Found: C, 61.88; H, 6.23; N, 14.41.
pyrrolidine-2,5-dione (23)
White solid. Yield: 80%; m.p. 185–187°C; Rf ¼ 0.57 (S1); 1H NMR
(300 MHz, CDCl3) d: 2.72–2.75 (m, 4H, CH2, imide, 4H, piperazine),
3.10–3.13 (m, 4H, piperazine), 4.49 (s, 2H, CH2), 6.67 (d, 1H, ArH,
J ¼ 2.82 Hz), 6.90 (d, 1H, ArH, J ¼ 2.82 Hz), 7.23 (d, 1H, ArH,
J ¼ 2.82 Hz); 13C NMR (75 MHz, CDCl3) d: 28.12, 48.76, 51.16, 59.93,
115.55, 117.39, 122.33, 130.43, 132.76, 150.52, 176.31; ESI-MS:
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