March 2009
Synthesis and Antimicrobial Activity of Novel Analogs of Trifenagrel
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Anal. Cacld. for: C27H27N3O2: C, 76.28; H, 6.31. Found: C,
76.28; H, 6.31.
H), 7.53–7.56 (d, J ¼ 7.55 Hz, 4H, Ar-H), 7.97–8.02 (m, 2H,
Ar-H), 13C NMR (75 MHz, CDCl3 þ DMSO-d6): d 19.71, 21.69,
66.60, 108.53, 112.11, 113.14, 120.12, 121.91, 125.49, 126.42,
126.79, 127.61, 128.86, 129.68, 132.04, 133.50, 136.23, 150.13,
157.10, 190.60. ESI-MS: m/z 424 [M þ H]þ. Anal. Cacld. for:
C28H29N3O: C, 79.40; H, 6.89. Found: C, 79.48; H, 6.94.
4-(2-Bromoethoxy) benzaldehyde (9). Prepared following
the procedure described for (3) using 4-hydroxybenzaldehyde
(6.20 g, 50.8 mmol), 1,2-dibromoethane (38.14 g, 203 mmol),
and methanol (50 mL) to obtain the titled compound (7.55 g,
65%) (9) as white solid. mp: 55–58ꢂC, IR (KBr): m 3349,
4-(2-Morpholino)ethoxy)benzaldehyde (11e). Prepared fol-
lowing the procedure described for (5b) using 4-(2-bromoe-
thoxy)-benzaldehyde (1.00 g, 4.3 mmol), morpholine (1.06 g,
12.18 mmol), and methanol (12.5 mL) to obtain the titled
compound (11e) (0.97 g, 97%) as brown syrup. IR (Neat): m
1
2927, 1601 cmꢀ1. H NMR (300 MHz, CDCl3): d 3.64 (t, 2H,
ACH2), 4.36 (t, 2H, ACH2), 7.00 (d, J ¼ 9.06 Hz, 2H, Ar-H),
7.81 (d, J ¼ 8.30 Hz, 2H, Ar-H), 9.82 (s, 1H, ACHO), 13C
NMR (75 MHz, CDCl3): d 28.59, 29.66, 67.98, 76.72, 77.14,
77.57, 114.90, 130.47, 131.98, 163.00, 190.63. EI-MS: m/z
229 [M]þ. Anal. Cacld. for: C9H9O2Br: C, 47.19; H, 3.95.
Found: C, 47.10; H, 4.01.
1
2953, 1689, 1600 cmꢀ1, H NMR (300 MHz, CDCl3): d 2.54
(t, 4H, 2 ꢁ ACH2), 2.79 (t, 2H, ACH2), 3.68 (t, 4H, 2 ꢁ
ACH2), 4.15 (t, 2H, ACH2), 6.95–7.00 (d, J ¼ 9.06 Hz, 2H,
Ar-H), 7.79 (d, J ¼ 8.30 Hz, 2H, Ar-H), 9.85 (s, 1H, ACHO).
ESI-MS: m/z 236 [M þ H]þ. Anal. Cacld. for: C13H17NO3: C,
66.36; H, 7.28. Found: C, 66.31; H, 7.30.
4-(2-Dimethylaminoethoxy)benzaldehyde (11a). Prepared
following the procedure described for (4a) using 4-(2-bromoe-
thoxy)-benzaldehyde (1.00 g, 4.36 mmol), 40% dimethylamine
solution (10 mL, 81.6 mmol), and methanol (20 mL) to obtain
the title compound (0.77 g, 92%) (11a) as brown liquid. IR
2-(4-[2-(Morpholino)ethoxy)phenyl]-4,5-diphenylimidazol
(12e). Prepared following the procedure described for (7a)
using benzil (0.42 g, 2.0 mmol), 4-(2-morpholinoethoxy) benz-
aldehyde (0.51 g, 2.1 mmol), ammoniumacetate (0.54 g, 7.0
mmol), catalyst phosphotungsticacid (0.1 g, 3 mol %) to obtain
the titled compound (11e) (0.65 g, 70%) as brown semisolid.
(Neat): u 3437, 1690, 1600 cmꢀ1 1H NMR (300 MHz,
,
CDCl3): d 2.33 (s, 6H, 2 ꢁ CH3), 2.78 (t, 2H, ACH2), 4.16 (t,
2H, ACH2), 6.99–6.94 (m, 2H, Ar-H), 7.36–7.39 (m, 2H, Ar-
H), 9.80 (s, 1H, ACHO). EI-MS: m/z 193 [M]þ. Anal. Cacld.
for: C11H15NO2: C, 68.37; H, 7.82. Found: C, 68.41; H, 7.80.
2-(4-[2-Dimethylaminoethoxy)phenyl]-4,5-diphenylimida-
zole (12a). Prepared following the procedure described for
(6a) using benzil (0.14 g, 0.67 mmol), 4-(2-dimethylaminoe-
thoxy) benzaldehyde (0.15 g, 0.77 mmol), ammonium acetate
(0.18 g, 2.30 mmol), catalyst PTA (0.1 g, 3 mol %) to obtain
the titled compound (0.22 g, 89%) (12a) as brown soliꢀd1. mp:
,
1H
IR (Neat): m 3059, 1603, 1247 cmꢀ1 1H NMR (200 MHz,
,
CDCl3 þ DMSO-d6): d 2.55 (t, 4H, 2 ꢁ ACH2), 2.78 (t, 2H,
ACH2), 3.68 (t, 4H, 2 ꢁ ACH2), 4.13 (t, 2H, ACH2), 6.90 (d,
J ¼ 8.86 Hz, 2H, Ar-H), 7.20–7.57 (m, 10H, Ar-H), 8.00 (m,
2H, Ar-H), 13C NMR (75 MHz, CDCl3 þ DMSO-d6): d 23.57,
53.42, 56.85, 65.22, 66.07, 100.85, 113.96, 122.97, 125.67,
125.88, 126.40, 127.33, 127.67, 128.31, 129.59,132.01, 129.95,
145.58, 158.23, 163.30. ESI-MS: m/z 426 [M þ H]þ. Anal. Cacld.
for: C27H27N3O2: C, 76.28; H, 6.31. Found: C, 76.28; H, 6.31.
4-(2-Bromoethoxy)-3-methoxybenzaldehyde (10). Prepared
following the procedure described for (3) using 4-(3-methoxy)
hydroxybenzaldehyde (8.00 g, 52.2 mmol), 1,2-dibromoethane
(39.19 g, 208.6 mmol), and methanol (50 mL) to obtain the ti-
tled compound (10) (9.30 g, 68%) as white crystalline solid.
120–125ꢂC, IR (Neat): m 3058, 2928, 1494, 1245 cm
NMR (200 MHz, CDCl3 þ DMSO-d6): d 2.32 (s, 6H, 2 ꢁ
CH3), 2.72 (t, 2H, ACH2), 4.08 (t, 2H, ACH2), 6.90 (d, J ¼
6.86 Hz, 3H, Ar-H), 7.24–7.28 (m, 5H, Ar-H), 7.54 (d, J ¼
7.55 Hz, 4H, Ar-H), 7.98 (d, J ¼ 10.98 Hz, 2H, Ar-H), 13C
NMR (75 MHz, CDCl3 þ DMSO-d6): d 21.81, 44.77, 64.77,
122.85, 125.64, 113.93, 126.46, 127.61, 127.37, 127.92,
128.04,129.77, 132.71, 145.73, 158.11. ESI-MS: m/z 384
[M þ H]þ. Anal. Cacld. for: C25H25N3O: C, 78.30; H, 6.57.
Found: C, 78.36; H, 6.51.
mp: 62–65ꢂC, IR (KBr): m 3342, 1680, 1270 cmꢀ1 1H NMR
,
(300 MHz, CDCl3): d 3.66 (t, 2H, ACH2), 3.92 (s, 3H,
AOCH3), 4.37 (t, 2H, ACH2), 6.94 (d, J ¼ 8.30 Hz, 2H, Ar-
H), 7.36–7.40 (m, 2H, Ar-H), 9.82 (s, 1H, ACHO), 13C NMR
(75 MHz, CDCl3): d 28.09, 56.03, 68.67, 109.77, 112.34,
126.30, 130.75, 149.92, 152.80, 190.75. ESI-MS: m/z 261 [M
þ H]þ. Anal. Cacld. for: C10H11O3Br: C, 46.35; H, 4.27.
Found: C, 46.30; H, 4.30.
4-(2-Piperidinoethoxy) benzaldehyde (11c). Prepared fol-
lowing the procedure described for (4b) using 4-(2-bromoe-
thoxy)-benzaldehyde (0.85 g, 3.71 mmol), piperidine (0.80 g,
9.41 mmol), and methanol (15 mL) to obtain the titled com-
pound (11c) (0.83 g, 95%) as brown syrup. IR (Neat): u 2934,
1
1692, 1601 cmꢀ1, H NMR (200 MHz, CDCl3 þ DMSO-d6):
4-(2-Dimethylaminoethoxy)-3-methoxybenzaldehyde
(11b). Prepared following the procedure described for (5a)
using 4-(2-bromoethoxy)-3-methoxybenzaldehyde (1.00 g, 3.84
mmol), 40% dimethylamine solution (10 mL, 81.6 mmol), and
methanol (20 mL) to obtain the title compound (11b) (0.77 g,
d 1.42–1.64 (m, 6H, 3 ꢁ CH2), 2.47 (t, 4H, 2 ꢁ ACH2), 2.74
(t, 2H, ACH2), 4.11 (t, 2H, ACH2), 7.09–7.15 (m, 2H, Ar-H),
7.34–7.45 (m, 2H, Ar-H), 9.93 (s, 1H, ACHO). ESI-MS: m/z
234 [M þ H]þ. Anal. Cacld. for: C14H19NO2: C, 72.07; H,
8.20. Found: C, 72.02; H, 8.01.
1
89%) as yellow syrup. IR (Neat): m 2941,1682, 1270 cmꢀ1, H
NMR (300 MHz, CDCl3): d 2.32 (s, 6H, 2 ꢁ CH3), 2.77 (t,
2H, ACH2), 3.91 (s, 3H, AOCH3), 4.15 (t, 2H, ACH2), 6.93
(d, 1H, Ar-H), 7.36 (d, 2H, Ar-H), 9.81 (s, 1H, ACHO), 13C
NMR (75 MHz, CDCl3): d 45.60, 55.76, 57.58, 66.66, 109.06,
111.28, 126.58, 129.96, 149.59, 153.60, 190.74. EI-MS: m/z
224 [M]þ. Anal. Cacld. for: C12H17NO3: C, 64.55; H, 7.67.
Found: C, 64.49; H, 7.73.
2-(4-[2-(Piperidino)ethoxy)phenyl]-4,5-diphenylimidazole
(12c). Prepared following the procedure described for (7a)
using benzil (0.42 g, 2.0 mmol), 4-(2-piperidinoethoxy)-benz-
aldehyde (0.51 g, 2.1 mmol), ammonium acetate (0.54 g, 7.0
mmol), catalyst PTA (0.1 g, 3 mol %) to obtain the titled com-
pound (0.74 g, 88%) (12c) as pale brown solid. mp: 188–
190ꢂC, IR (Neat): m 3419, 1651, 1025 cmꢀ1 1H NMR (200
,
MHz, CDCl3 þ DMSO-d6): d 1.38 (m, 6H, 3 ꢁ CH2), 2.50 (t,
4H, 2 ꢁ ACH2), 2.74 (t, 2H, ACH2), 4.11 (t, 2H, ACH2),
6.90–6.94 (d, J ¼ 8.86 Hz, 2H, Ar-H), 7.21–7.33 (m, 6H, Ar-
2-(4-[2-Dimethylaminoethoxy)-3-methoxyphenyl]-4,5-di-
phenylimidazole (12b). Prepared following the procedure
described for (7a) using benzil (0.42 g, 2.0 mmol), 4-(2-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet