RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2015, 348, 868–874
M. M. W. Habib et al.
Archiv der Pharmazie
CDCl3) d: 2.94–2.96 (m, 4H, piperazine), 3.17–3.18 (m, 4H,
piperazine), 4.97 (s, 2H, CH2), 6.75 (s, 1H, CH), 6.76–7.48 (m,
10H, aromatic), 8.72 (s, brs, 1H, NH). EI-MS: m/z (%) 377.90,
Mþ, (0.56). Anal. calcd. for C21H22N4OS (378.49): C: 66.64, H:
5.86, N: 14.80; Found: C: 66.86, H: 5.15, N: 14.53.
5-Benzylidene-3-[4-(2-methoxyphenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (7)
Brown solid. Yield: 90%; mp 135–137°C; TLC: Rf ¼ 0.33; IR:
3332 (NH), 2827, 2921 (CH ), 1724 (C O). 1H NMR (300 Hz,
–
–
2
CDCl3) d: 3.42–3.43 (m, 4H, piperazine), 3.85–3.87 (m, 4H,
piperazine), 3.88 (s, 3H, OCH3), 5.44 (s, 2H, CH2), 6.70 (s, 1H,
CH), 6.80–7.48 (m, 9H, aromatic), 9.83 (s, brs, 1H, NH). EI-MS:
m/z (%) 407.90, Mþ, (15.55). Anal. calcd. for C22H24N4O2S
(408.52): C: 64.68, H: 5.92, N: 13.71; Found: C: 64.21, H: 5.52, N:
13.96.
5-Benzylidene-3-[4-(2-chlorophenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (2)
Brown solid. Yield: 79%; mp 218–220°C; TLC: Rf ¼ 0.31; IR:
3334 (NH), 2813, 2930 (CH ), 1720 (C O). 1H NMR (300 Hz,
–
–
2
CDCl3) d: 3.39–3.41 (m, 4H, piperazine), 3.44–3.46 (m, 4H,
piperazine), 5.44 (s, 2H, CH2), 6.71 (s, 1H, CH), 6.81–7.48 (m, 9H,
aromatic), 9.88 (s, brs, 1H, NH). EI-MS: m/z (%) 412.00, Mþ,
(28.57) and 414.00, Mþþ2, (22.71). Anal. calcd. for
5-Benzylidene-3-[4-(2-ethoxyphenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (8)
Brown solid. Yield: 71%; mp 179–181°C; TLC: Rf ¼ 0.36; 1H
NMR (300 Hz, CDCl3) d: 1.44–1.46 (t, 3H, OCH2CH3), 3.42–3.44
(m, 4H, piperazine), 3.59–3.61 (m, 4H, piperazine), 4.07–4.09
(q, 2H, OCH2CH3), 5.43 (s, 2H, CH2), 6.77 (s, 1H, CH), 6.81–7.49
(m, 9H, aromatic), 8.77 (s, brs, 1H, NH). EI-MS: m/z (%) 421.00,
Mþ, (44.29). Anal. calcd. for C23H26N4O2S (422.54): C: 65.38, H:
6.20, N: 13.26; Found: C: 65.72, H: 6.63, N: 13.23.
C
21H21ClN4OS (412.94): C: 61.08, H: 5.13, N: 13.57; Found: C:
61.25, H: 5.15, N: 13.53.
5-Benzylidene-3-[4-(2-fluorophenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (3)
Orange solid. Yield: 83%; mp 188–190°C; TLC: Rf ¼ 0.33; IR:
3375 (NH), 2823, 2951 (CH ), 1710 (C O). 1H NMR (300 Hz,
–
–
2
CDCl3) d: 2.98–2.99 (m, 4H, piperazine), 3.08–3.09 (m, 4H,
piperazine), 4.98 (s, 2H, CH2), 6.76 (s, 1H, CH), 6.92–7.52 (m, 9H,
aromatic). EI-MS: m/z (%) 395.80, Mþ, (21.80). Anal. calcd. for
5-(4-Chlorobenzylidene)-3-(4-phenylpiperazin-1-
ylmethyl)-2-thioxo-imidazolidin-4-one (9)
Bright yellow solid. Yield: 69%; mp 184–186°C; TLC: Rf ¼ 0.50;
1
–
C
21H21FN4OS (396.48): C: 63.62, H: 5.34, N: 14.13; Found: C:
IR: 3223 (NH), 2824, 2946 (CH ), 1710 (C O). H NMR (300 Hz,
–
2
63.89, H: 5.53, N: 14.47.
CDCl3) d: 3.17–3.20 (m, 4H, piperazine), 3.92–3.96 (m, 4H,
piperazine), 4.97 (s, 2H, CH2), 6.71 (s, 1H, CH), 6.84–7.47 (m, 9H,
aromatic). EI-MS: m/z (%) 412.10, Mþ, (1.70). Anal. calcd. for
5-Benzylidene-3-[4-(4-fluorophenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (4)
C
21H21ClN4OS (412.94): C: 61.08, H: 5.13, N: 13.57; Found: C:
Yellow solid. Yield: 95%; mp 205–207°C; TLC: Rf ¼ 0.62; IR:
61.35, H: 5.42, N: 13.39.
3226 (NH), 2818, 2951 (CH ), 1708 (C O). 1H NMR (300 Hz,
–
–
2
CDCl3) d: 2.93–2.96 (m, 4H, piperazine), 3.08–3.11 (m, 4H,
piperazine), 4.97 (s, 2H, CH2), 6.75 (s, 1H, CH), 6.83–7.51 (m, 9H,
aromatic), 8.73 (s, brs, 1H, NH). EI-MS: m/z (%) 395.90, Mþ,
(0.42). Anal. calcd. for C21H21FN4OS (396.48): C: 63.62, H: 5.34,
N: 14.13; Found: C: 63.24, H: 5.59, N: 14.44.
5-(4-Chlorobenzylidene-3-[4-(2-chlorophenyl)-piperazin-
1-ylmethyl]-2-thioxoimidazolidin-4-one (10)
Brown solid. Yield: 64%; mp 146–148°C; TLC: Rf ¼ 0.34; IR:
3267 (NH), 2811, 2930 (CH ), 1727 (C O). 1H NMR (300 Hz,
–
–
2
CDCl3) d: 3.15–3.17 (m, 4H, piperazine), 3.21–3.23 (m, 4H,
piperazine), 6.47 (s, 2H, CH2), 7.08 (s, 1H, CH), 7.12–7.77 (m, 8H,
aromatic). EI-MS: m/z (%) 447.00, Mþ, (67.62) and 449.00,
Mþþ2, (49.52). Anal. calcd. for C21H20Cl2N4OS (447.38): C:
56.38, H: 4.51, N: 12.52; Found: C: 56.71, H: 4.61, N: 12.05.
5-Benzylidene-3-[4-(2-hydroxyphenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (5)
Red solid. Yield: 75%; mp 112–114°C; TLC: Rf ¼ 0.48; IR: 3343
1
–
(NH), 2825, 2945 (CH ), 1739 (C O). H NMR (300 Hz, CDCl ) d:
–
2
3
2.75–2.96 (m, 4H, piperazine), 3.72–3.76 (m, 4H, piperazine),
5.45 (s, 2H, CH2), 6.74 (s, 1H, CH), 6.88–7.47 (m, 9H, aromatic).
EIMS: m/z (%) 394.00, Mþ, (64.04). Anal. calcd. for
5-(4-Chlorobenzylidene)-3-[4-(2-fluorophenyl)-piperazin-
1-ylmethyl]-2-thioxoimidazolidin-4-one (11)
Yellowish brown solid. Yield: 66%; mp 193–195°C; TLC:
–
C
21H22N4O2S (394.49): C: 63.94, H: 5.62, N: 14.20; Found: C:
R ¼ 0.45; IR: 3373 (NH), 2818, 2948 (CH ), 1707 (C O). 1H
–
f
2
63.90, H: 5.79, N: 14.52.
NMR (300 Hz, DMSO) d: 2.79–2.81 (m, 4H, piperazine), 2.97–
2.99 (m, 4H, piperazine), 4.79 (s, 2H, CH2), 6.63 (s, 1H, CH),
6.96–7.82 (m, 8H, aromatic). EI-MS: m/z (%) 430.00, Mþ,
(30.57) and 432.00, Mþþ2, (19.62). Anal. calcd. for
5-Benzylidene-3-[4-(4-hydroxyphenyl)-piperazin-1-
ylmethyl]-2-thioxoimidazolidin-4-one (6)
Red solid. Yield: 68%; mp 180–182°C; TLC: Rf ¼ 0.40; IR: 3342
C21H20ClFN4OS (430.93): C: 58.53, H: 4.68, N: 13.00; Found:
1
–
(NH), 2819, 2944 (CH ), 1726 (C O). H NMR (300 Hz, CDCl ) d:
C: 58.83, H: 4.85, N: 12.78.
–
2
3
2.72–2.95 (m, 4H, piperazine), 3.72–3.77 (m, 4H, piperazine),
5.44 (s, 2H, CH2), 6.64 (s, 1H, CH), 6.78–7.46 (m, 9H, aromatic).
EIMS: m/z (%) 394.90, Mþ, (66.67). Anal. calcd. for
5-(4-Chlorobenzylidene)-3-[4-(4-fluorophenyl)-piperazin-
1-ylmethyl]-2-thioxoimidazolidin-4-one (12)
C
21H22N4O2S (394.49): C: 63.94, H: 5.62, N: 14.20; Found: C:
Yellow solid. Yield: 76%; mp 195–197°C; TLC: Rf ¼ 0.43; IR:
3349 (NH), 2827, 2955 (CH ), 1713 (C O). 1H NMR (300 Hz,
–
–
63.64, H: 5.32, N: 14.41.
2
ß 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
872