Functionalized Heterocycles
5323 5331
pound 11d as a yellow solid (2.19 g,5.89 mmol,59%). M.p. 108 8C;
1H NMR (CDCl3,300 MHz): d 8.59 (s,2H),7.41 (dm, J 8.8 Hz,2H),
7.17 (d, J 16.8 Hz,1H),6.90 (d, J 8.8 Hz,2H),6.67 (d, J 16.8 Hz,1H),
4.47 (q, J 7.1 Hz,2H),3.83 (s,3H),1.44 ppm (t, J 7.1 Hz,3H); 13C NMR
(CDCl3,75 MHz): d 162.5,160.9,150.2,137.6,131.7,130.7,128.9,128.1,
1.8 Hz,1H),7.44 (dm, J 8.8 Hz,2H),6.98 (d, J 16.6 Hz,1H),6.91 (dm,
J 8.8 Hz,2H),6.73 (d, J 16.6 Hz,1H),4.43 (q, J 7.1 Hz,2H),3.83 (s,
3H),1.42 ppm (t, J 7.1 Hz,3H); 13C NMR (CDCl3,75 MHz): d 163.3,
160.5,150.2,137.1,136.6,136.5,130.4,128.6,128.4,125.4,123.6,119.4,114.2,
62.2,55.3,14.2 ppm; IR (KBr): nÄ 3420(m),3076(m),2982(m),2937(m),
2842(w),1718(vs),1631(m),1600(s),1574(m),1532(s),1513(s),1462(m),
1422(m),1362(s),1250(vs),1178(s),1142(m),1034(m),970(m),907(w),
822(m),767(m),748(m),726(m),545 cm À1 (w); MS (EI): m/z (%): 407/405
127.7,114.7,114.3,62.7,55.34,14.2 ppm; IR (KBr):
nÄ 3431(w),2977(w),
1715(s),1604(s),1539(s)1,515(s),1460(m),1425(w),1353(m),1286(s),
1255(s),1179(s),1033(m),978(m),918(w),834(m),768(w),749(m),
723(m),540 cm À1 (w); MS (EI): m/z (%): 372 [M] (9),163 (15),152 (10),
[M] (6/7),390 (14),388 (14),362 (14),360 (15),271 (13),269 (13),243 (17),
137 (27),136 (75),135 (100),121 (17); HRMS (EI) calcd for C 18H16N2O7:
241 (11),216 (11),214 (10),164 (24),163 (41),152 (14),136 (64),135 (100),
134 (31),121 (48),77 (10); HRMS (EI) calcd for C 18H16BrNO5: 405.0212;
372.0958; found: 372.0915 [M] ; elemental analysis calcd (%) for
C18H16N2O7 (372.34): C 58.06,H 4.33,N 7.52; found: C 58.05,H 4.54,N 7.56.
found: 405.0219 [M] .
1,3-Dinitro-2-[(E)-2-phenylethenyl]benzene (11e):[10a,10e] Compound 13c
(1.82 g,10.0 mmol) with benzaldehyde (3.18 g,30.0 mmol) and piperidine
(1.28 g,15.0 mmol) in the presence of molecular sieves (4 ä,2.00 g) at
1108C for 4 d was treated as described in procedure D. After the mixture
had cooled to room temperature,THF (25 mL) was added,the reaction
mixture was filtered,and the remaining residue was washed with CH 2Cl2
(3 Â 25 mL). The filtrate was concentrated in vacuo and the crude product
was purified by flash chromatography (silica gel,pentane/ethyl acetate
95:5) to afford compound 11e as a yellow solid (540 mg,2.0 mmol,20%).
1H NMR (CDCl3,300 MHz): d 7.99 (d, J 7.8 Hz,2H),7.54 (t, J 7.8 Hz,
1H),7.45 7.40 (m,2H),7.37 7.28 (m,4H),6.58 ppm (d, J 16.2 Hz,1H);
13C NMR (CDCl3,75 MHz): d 150.3,135.9,135.5,129.0,128.7,128.5,
128.1,127.3,127.0,118.3 ppm.
Ethyl 3-bromo-5-nitro-4-[(E)-2-(3-pyridinyl)ethenyl]benzoate (11b):
Compound 13a (864 mg,3.00 mmol) was treated with nicotinaldehyde
(964 mg,9.00 mmol) and piperidine (383 mg,4.50 mmol) in the presence of
molecular sieves (4 ä,600 mg) in toluene (5 mL) as described in
procedure D. The solution was heated at 1108C for 4 d. As the conversion,
as determined by GC,was still incomplete,the mixture was heated at 140 8C
for 1 d,after which the conversion remained still incomplete (43%). After
the mixture had cooled to room temperature,THF (5 mL) was added,the
reaction mixture was filtered,and the remaining residue was washed with
CH2Cl2 (3 Â 5 mL). The solvent was removed under reduced pressure and
the crude product was purified by flash column chromatography (silica gel,
pentane/ethyl acetate 65:35) and was subsequently recrystallized to afford
compound 11b as a light yellow solid (238 mg,0.63 mmol,21%). M.p.
1018C; 1H NMR (CDCl3,300 MHz): d 8.72 8.69 (m,1H),8.57 (dd, J
4.9,1.8 Hz,1H),8.48 (d, J 1.8 Hz,1H),8.35 (d, J 1.8 Hz,1H),7.87 7.82
(m,1H),7.33 (dd, J 8.0,4.9 Hz,1H),7.20 (d, J 16.8 Hz,1H),6.75 (d, J
Typical procedure E: N,N-Dimethyl-4-iodo-6-(trifluoromethyl)-1H-benz-
imidazole-2-amine (7a): Compound 6a (387 mg,1.0 mmol) in THF (2 mL)
was treated at À408C with PhMgCl (1.20 g,25% in THF,2.2 mmol). After
15 min the reaction was quenched by the addition of methanol (0.5 mL),
and the solvent was removed under reduced pressure. The crude product
was purified by flash column chromatography (silica gel,pentane/ethyl
acetate 50:50). Compound 7a was isolated as a white solid (266 mg,
0.75 mmol,75%). M.p. 226 8C; 1H NMR (CDCl3/[D6]DMSO,300 MHz):
16.8 Hz,1H),4.44 (q,
J 7.1 Hz,2H),1.43 ppm (t,
J 7.1 Hz,3H);
13C NMR (CDCl3,75 MHz): d 163.1,150.2,150.0,148.9,137.0,135.9,
133.6,133.3,131.4,125.5,124.2,123.8,123.7,62.3,14.2 ppm; IR (KBr):
3410(w),3080(m),2998(m),1729(s),1608(m),1533(vs),1480(m),
1465(m),1384(m),1364(s),1274(s),1206(m),1152(s),1023(m),906(m),
nÄ
870(m),854(m),770(m),748(m),729 cm À1 (m); MS (EI): m/z (%): 378/376
d 9.60 (brs,1H),7.54 (s,1H),7.28 (s,1H),3.10 ppm (s,6H);
(CDCl3/[D6]DMSO,75 MHz): d 157.6,146.2,134.5,126.1 (q, J 3.9 Hz),
125.8,122.5,122.1,106.9,38.1 ppm; IR (KBr):
13C NMR
[M] (8/8),361/359 (67/68),333/331 (64/65),305/303 (28/27),271/269 (81/
81),260 (27),256/254 (26/23),243/241 (64/65),226/224 (41/38),216/214 (70/
73),199/197 (52/54),178 (70),177 (55),166 (35),151 (66),150 (78),139 (28),
125 (18),106 (74),92 (100),78 (53),75 (42),63 (19),51 (15); HRMS (EI)
nÄ 3435(w),2933(m),
1637(s),1606(s),1570(m),1433(s),1370(m),1317(vs),1269(m),1238(m),
1189(m),1153(s),1118(s),1074(m),963(w),924(m),863(m),758(w),
687(m),664(w),452 cm À1 (w); MS (EI): m/z (%): 355 [M] (100),340 (62),
calcd for C18H13BrN2O5: 376.0059; found: 376.0068 [M] .
326 (49),213 (22),186 (15); elemental analysis calcd (%) for C 10H9F3IN3
(355.10): C 33.82,H 2.55,N 35.74; found: C 33.85,H 2.61,N 35.81.
Ethyl 3-bromo-5-nitro-4-[(E)-2-phenylethenyl]benzoate (11c): Compound
13a (720 mg,2.50 mmol) was treated with benzaldehyde (795 mg,
7.50 mmol) and piperidine (319 mg,3.75 mmol) in the presence of
molecular sieves (4 ä,600 mg) in toluene (5 mL) at 80 8C for 4 d as
described in procedure D. After the mixture had cooled to room temper-
ature,THF (5 mL) was added,the reaction mixture was filtered,and the
remaining residue was washed with CH2Cl2 (3 Â 5 mL). The solvent was
removed under reduced pressure and the crude product was purified by
flash column chromatography (silica gel,pentane/ethyl acetate 96:4),which
afforded compound 11c as a yellow solid (629 mg,1.67 mmol,67%). M.p.
Ethyl 2-(dimethylamino)-4-iodo-1H-benzimidazole-6-carboxylate (7b):
Compound 6b (391 mg,1.0 mmol) in THF (2 mL) was treated at À408C
with PhMgCl (1.20 g,25% in THF,2.2 mmol) for 15 min as described in
procedure E. After workup,the crude product was purified by flash column
chromatography (silica gel,pentane/ethyl acetate 50:50). Compound 7b
was isolated as a white solid (285 mg,0.79 mmol,79%). M.p. 250 251 8C;
1H NMR (CDCl3/[D6]DMSO,300 MHz): d 7.87 (d, J 1.5 Hz,1H),7.55
(d, J 1.5 Hz,1H),4.09 (q, J 7.2 Hz,2H),2.94 (s,6H),1.14 ppm (t,
J
1
7.2 Hz,3H); 13C NMR (CDCl3/[D6]DMSO,75 MHz): d 165.6,157.6,
1248C; H NMR (CDCl3,300 MHz): d 8.46 (d, J 1.8 Hz,1H),8.30 (d,
J 1.8 Hz,1H),7.54 7.48 (m,2H),7.43 7.31 (m,3H),7.13 (d,
J 16.4 Hz,
148.2,133.1,130.9,121.7,110.2,59.9,37.6,13.8 ppm; IR (KBr):
2930(w),1687(m),1636(s),1601(s),1558(m),1432(m),1368(m),1293(s),
nÄ 3429(m),
1H),6.78 (d, J 16.4 Hz,1H),4.44 (q, J 7.1 Hz,2H),1.43 ppm (t, J
7.1 Hz,3H); 13C NMR (CDCl3,75 MHz): d 163.3,150.3,137.4,136.7,
136.4,135.6,130.8,129.2,128.8,127.1,125.5,123.6,121.9,62.2,14.2 ppm; IR
À1
1228(m),1181(m),1096(w),1020(w),925(w),862(w),767 cm
(w); MS
(EI): m/z (%): 359 [M] (100),344 (22),330 (29),316 (25),302 (17),286
(KBr): nÄ 3428(w),3080(w),1721(s),1539(m),1366(m),1279(m),
(11),144 (8); HRMS (EI) calcd for C 12H14IN3O2: 359.0131; found: 359.0138
[M] ; elemental analysis calcd (%) for C12H14IN3O2 (359.16): C 40.13,H
3.93,N 35.33; found: C 40.06,H 3.81,N 35.46.
À1
1257(m),1149(m),1024(w),974(w),758(m),727(w),694 cm
(w); MS
(EI): m/z (%): 377/375 [M] (5/5),360/358 (43/43),332/330 (51/51),304/302
(28/28),271/269 (42/42),243/241 (39/39),226 (20),224 (27),216/214 (38/41),
199/197 (27/28),177 (40),176 (100),165 (38),163 (21),151 (33),134 (10),
105 (33),91 (69),88 (38),77 (31); HRMS (EI) calcd for C 17H14BrNO4:
2-(Dimethylamino)-4-iodo-1H-benzimidazole-6-carbonitrile (7c): Com-
pound 6c (344 mg,1.0 mmol) in THF (2 mL) was treated at À408C with
PhMgCl (1.20 g,25% in THF,2.2 mmol) for 15 min as described in
procedure E. After workup,the crude product was purified by flash column
chromatography (silica gel,pentane/ethyl acetate 50:50). Compound 7c
was isolated as a white solid (151 mg,0.48 mmol,48%). M.p. 261 8C;
1H NMR ([D6]DMSO,300 MHz): d 7.91 (d, J 1.5 Hz,1H),7.61 (d, J
1.5 Hz,1H),3.13 ppm (s,6H); 13C NMR ([D6]DMSO,300 MHz): d 156.9,
375.0106; found: 375.0092 [M] .
Ethyl 4-[(E)-2-(4-methoxyphenyl)ethenyl]-3,5-dinitrobenzoate (11d):
Compound 13b (2.54 g,10.0 mmol) was treated with 4-methoxybenzalde-
hyde (4.08 g,30.0 mmol) and piperidine (1.28 g,15.0 mmol) in the presence
of molecular sieves (4 ä,2.00 g) in toluene (25 mL) at 80 8C for 1 d as
described in procedure D. After the mixture had cooled to room temper-
ature,THF (25 mL) was added,the reaction mixture was filtered,and the
remaining residue was washed with CH2Cl2 (3 Â 25 mL). The filtrate was
concentrated in vacuo and the crude product was purified by flash
chromatography (silica gel,pentane/ethyl acetate 95:5) to afford com-
146.1,134.7,130.7,120.3,118.6,104.0,95.7,37.6 ppm; IR (KBr):
3435(m),2924(w),2229(m),1642(s),1592(vs),1544(s),1481(w),
nÄ
À1
1423(m),1376(s),1197(w),1114(m),832(w),781 cm
(w); MS (EI):
m/z (%): 312 [M] (100),297 (63),283 (54),170 (20),143 (14); HRMS (EI)
calcd C10H9IN4 311.9872; found: 311.9881 [M] ; elemental analysis calcd
Chem. Eur. J. 2003, 9,5323 5331
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
5329