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HUANG ET AL.
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constants were expressed in Hertz (Hz). The low‐resolution mass
spectrum (MS) was recorded on a Waters ZQ LC/MS single quad-
rupole system equipped with an electrospray ionization source. The
elemental analysis of the final derivatives was performed using a
Vario Elemental analyzer. The thin‐layer chromatography was per-
formed on 0.25‐mm Merck silica gel plates (60F‐254) and visualized
under ultraviolet light.
J = 8.13 Hz, Ar‐H), 4.13 (s, 1H, piperidine‐H), 3.84 (s, 2H, CH2,
thioxothiazolidine), 3.63 (s, 2H, CH2), and 2.52–1.89 (m, 8H, 4 × CH2,
piperidine‐H); 13C NMR (100 MHz, CDCl3) δ ppm: 201.5, 170.8,
136.9, 132.7, 131.3, 128.5, 64.7, 52.2, 51.8, 38.9, and 26.9; Mass:
341.92 (M+H)+; Elemental analysis for C15H17ClN2OS2: Calculated:
C, 52.85; H, 5.03; N, 8.22. Found: C, 52.87; H, 5.01; N, 8.23.
The InChI keys of the investigated compounds, together with
some biological data, are provided as Supporting Information.
3‐[1‐(3,4‐Dichlorobenzyl)piperidin‐4‐yl]‐2‐thioxothiazolidin‐4‐
one (6c)
Yield: 73%; M.p: 212–213°C; MW: 375.33; Rf: 0.69 (ethylacetate/
N‐hexane/methanol 3:2:1); FTIR (νmax, cm−1, KBr): 3,124 (aromatic C–H
stretching), 2,959 (alkyl C–H stretching), 1,719 (C═O stretching), 1,647
(C═C), 1,272 (C═S stretching), 1,078 (C–N stretching), 789 (C–Cl
stretching), 634 (C–S stretching), and 627; 1H NMR (400 MHz, CDCl3‐
d6, TMS) δ ppm: 7.48 (d, 1H, J = 1.32 Hz, Ar‐H), 7.44 (d, 1H, J = 8.20 Hz,
Ar‐H), 7.23 (d, 1H, J = 1.31 Hz, Ar‐H), 4.12 (s, 1H, piperidine‐H), 3.83
(s, 2H, CH2, thioxothiazolidine), 3.61 (s, 2H, CH2), and 2.57–1.85 (m, 8H,
4 × CH2, piperidine‐H); 13C NMR (100 MHz, CDCl3) δ ppm: 201.5, 170.7,
136.9, 132.6, 131.4, 128.6, 64.8, 52.2, 51.9, 38.8, and 26.6; Mass: 376.36
(M+H)+; Elemental analysis for C15H16Cl2N2OS2: Calculated: C, 48.00;
H, 4.30; N, 7.46. Found: C, 48.03; H, 4.28; N, 7.48.
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4.1.2
Synthesis of compounds 1, 2, 3, 4, and 5
The compounds 1, 2, 3a–h, 4a–h, and 5a–h were synthesized as per
the previously reported procedures given elsewhere.[27,28]
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4.1.3
General procedure for the synthesis of the 2‐
thioxo‐1,3‐thiazolidin‐4‐one derivatives (6a–h)
To a stirred solution of sodium chloroacetate (0.1 mol) in H2O (35 ml), a
solution of compound 4 (0.1 mol), separately dissolved in water/ethanol
(1:1), was slowly added, and the resulting mixture was allowed to stir at
70°C. After completion of the reaction (thin‐layer chromatography), the
mixture was cooled to room temperature and cautiously poured into
boiling hydrochloric acid (12 N, 40 ml). After 5 min, the solution was
allowed to cool slowly to room temperature to precipitate the desired
2‐thioxo‐1,3‐thiazolidin‐4‐one derivatives (6a–h). The precipitated solid
was filtered and washed with water, followed by cold ethanol, dried, and
recrystallized (ethanol) to furnish pure product.
3‐[1‐(4‐Bromobenzyl)piperidin‐4‐yl]‐2‐thioxothiazolidin‐4‐one (6d)
Yield: 87%; M.p: 224–225°C; MW: 385.34; Rf: 0.64 (ethylacetate/N‐
hexane/methanol 3:2:1); FTIR (νmax, cm−1, KBr): 3,128 (aromatic C–H
stretching), 2,952 (alkyl C–H stretching), 1,718 (C═O stretching),
1,648 (C═C), 1,276 (C═S stretching), 1,073 (C–N stretching), 758
(C–Br stretching), 636 (C–S stretching), and 629; 1H NMR (400 MHz,
CDCl3, TMS) δ ppm: 7.45 (d, 2H, J = 1.37 Hz, Ar‐H), 7.31 (d, 2H,
J = 8.21 Hz, Ar‐H), 4.12 (s, 1H, piperidine‐H), 3.82 (s, 2H, CH2,
thioxothiazolidine), 3.61 (s, 2H, CH2), and 2.58–1.87 (m, 8H, 4 × CH2,
piperidine‐H); 13C NMR (100 MHz, CDCl3) δ ppm: 201.2, 170.8,
137.8, 131.4, 131.1, 121.6, 52.1, 51.8, 38.9, and 26.8; Mass: 386.32
(M+H)+; Elemental analysis for C15H17BrN2OS2: Calculated: C, 46.76;
H, 4.45; N, 7.27. Found: C, 46.76; H, 4.45; N, 7.28.
3‐(1‐Benzylpiperidin‐4‐yl)‐2‐thioxothiazolidin‐4‐one (6a)
Yield: 85%; M.p: 195–196°C; MW: 306.44; Rf: 0.79 (ethylacetate/N‐
hexane/methanol 3:2:1); Fourier‐transform infrared spectroscopy
(FTIR; νmax, cm−1, KBr): 3,123 (aromatic C–H stretching), 2,958 (alkyl
C–H stretching), 1,714 (C═O stretching), 1,645 (C═C), 1,271 (C═S
stretching), 1,078 (C–N stretching), 635 (C–S stretching), and 628; 1H
NMR (400 MHz, CDCl3, tetramethylsilane [TMS]) δ ppm: 7.23 (d, 2H,
J = 7.77 Hz, Ar‐H), 7.21 (d, 2H, J = 7.69 Hz, Ar‐H), 7.29 (d, 1H,
J = 6.03 Hz, Ar‐H), 4.12 (s, 1H, piperidine‐H), 3.82 (s, 2H, CH2,
thioxothiazolidine), 3.65 (s, 2H, CH2), and 2.51–1.84 (m, 8H, 4 × CH2,
piperidine‐H); 13C NMR (100 MHz, CDCl3) δ ppm: 201.4, 170.6,
138,6, 128.8, 128.4, 127.2, 64.7, 52.1, 51.6, 38.9, and 26.8; Mass:
307.51 (M+H)+; Elemental analysis for C15H18N2OS2: Calculated: C,
58.79; H, 5.92; N, 9.14. Found: C, 58.83; H, 5.94; N, 9.13.
3‐[1‐(4‐Fluorobenzyl)piperidin‐4‐yl]‐2‐thioxothiazolidin‐4‐one (6e)
Yield: 73%; M.p: 202–203°C; MW: 324.43; Rf: 0.89 (ethylacetate/N‐
hexane/methanol 3:2:1); FTIR (νmax, cm−1, KBr): 3,124 (aromatic C–H
stretching), 2,957 (alkyl C–H stretching), 1,715 (C═O stretching),
1,647 (C═C), 1,278 (C═S stretching), 1,157 (C–F stretching), 1,072
(C–N stretching), 639 (C–S stretching), and 621; 1H NMR (400 MHz,
TMS) δ ppm: 7.38 (d, 2H, J = 1.04 Hz, Ar‐H), 7.07 (d, 2H, J = 1.24 Hz,
Ar‐H), 4.13 (s, 1H, piperidine‐H), 3.83 (s, 2H, CH2, thioxothiazolidine),
3.61 (s, 2H, CH2), and 2.57–1.86 (m, 8H, 4 × CH2, piperidine‐H); 13C
NMR (100 MHz, CDCl3) δ ppm: 201.5, 170.9, 161.4, 134.3, 130.4,
115.2, 64.8, 52.1, 51.8, 38.9, and 26.9; Mass: 325.47 (M+H)+; Ele-
mental analysis for C15H17FN2OS2: Calculated: C, 55.53; H, 5.28; N,
8.63. Found: C, 55.58; H, 5.25; N, 8.61.
3‐[1‐(4‐Chlorobenzyl)piperidin‐4‐yl]‐2‐thioxothiazolidin‐4‐one (6b)
Yield: 75%; M.p: 209–210°C; MW: 340.88; Rf: 0.83 (ethylacetate/N‐
hexane/methanol 3:2:1); FTIR (νmax, cm−1, KBr): 3,118 (aromatic C–H
stretching), 2,954 (alkyl C–H stretching), 1,716 (C═O stretching),
1,642 (C═C), 1,273 (C═S stretching), 1,076 (C–N stretching), 787
(C–Cl stretching), 632 (C–S stretching), and 623; 1H NMR (400 MHz,
CDCl3‐d6, TMS) δ ppm: 7.44 (d, 2H, J = 8.29 Hz, Ar‐H), 7.43 (d, 2H,
3‐[1‐(4‐Nitrobenzyl)piperidin‐4‐yl]‐2‐thioxothiazolidin‐4‐one (6f)
Yield: 84%; M.p: 231–233°C; MW: 351.44; Rf: 0.82 (ethylacetate/N‐
hexane/methanol 3:2:1); FTIR (νmax, cm−1, KBr): 3,126 (aromatic C–H