Synthesis of Di(indolyl)pyrazolyl Methanes in Ionic Liquid
275
R5
H2PtCl6/[bmim][Cl]
rt, 10–30 min
ϩ
R5CHO
N
H
N
H
N
H
1a
4a–4f
5a–5f
89–95%
Scheme 2.
General Procedure
C 77.45, H 5.32, N 13.36. C27H22N4O requires C 77.49, H 5.30, N
13.39%.)
Synthesis of 1-Butyl-3-methylimidazolium Chloride [bmim][Cl]
1-Methylimidazole (25 g, 0.30 mol) was mixed with n-butyl chloride
(42 g, 0.46 mol) and allowed to reflux for 24 h under nitrogen atmo-
sphere. The excess n-butyl chloride was distilled off under reduced
pressure and the residue was extracted thoroughly with diethyl ether
(3 × 75 mL) to remove the unreacted starting materials. A clear yel-
low viscous oily liquid of 1-butyl-3-methylimidazolium chloride was
obtained in 90% yield. The moisture content of the ionic liquid (0.06%)
was determined by Karl–Fisher titration.
3-[1H-Indol-3-yl(3-(4-methoxyphenyl)-1H-pyrazol-4-yl)methyl]-
1H-indole3d
Brown solid, mp 207–209◦C. νmax (KBr)/cm−1 3414, 3034, 1612,
1427, 1415, 1338, 1238, 1088, 1018, 745. δH ([D6]DMSO) 12.83 (1H,
br s, pyrazole NH), 10.80 (2H, s, indole NH), 7.50 (2H, d, J 8.0), 7.42
(1H, s), 7.32 (2H, t, J 7.6), 7.20 (2H, d, J 7.7), 7.02 (2H, t, J 7.6), 6.91
(2H, t, J 7.6), 6.88 (2H, s), 6.85 (2H, t, J 7.7), 5.83 (1H, s), 3.73 (3H, s).
δC ([D6]DMSO) 162.8, 159.1, 137.2, 130.2, 128.9, 126.9, 123.8, 121.3,
119.4, 119.2, 118.6, 114.5, 112.5, 111.9, 110.0, 55.5, 30.2. m/z 418
(M+). (Found: C 77.46, H 5.28, N 13.41. C27H22N4O requires C 77.49,
H 5.30, N 13.39%.)
Synthesis of 1-Methyl-3-[(1-methyl-1H-indol-3-yl)
(3-Phenyl-1H-pyrazol-4-yl)methyl]-1H-indole 3e
A mixture of 1-methylindole 1b (200 mg, 1.53 mmol), 3-phenyl-
1H-pyrazole-4-carbaldehyde 2a (131 mg, 0.76 mmol), and H2PtCl6
(2 mol%) mixed with [bmim][Cl] (3 mL) was stirred at room temper-
ature for 30 min. After complete conversion, as indicated by TLC, the
mixture was extracted with ethyl acetate (3 × 20 mL). The ionic liquid
was insoluble in ethyl acetate. The combined organic layers were dried
over anhydrous Na2SO4, concentrated and purified by column chro-
matography on silica gel (100–200 mesh, Merck, ethyl acetate/hexane
(3/7)) to get pure brown solid 3e in excellent yield (92%). Finally, the
ionic liquid was heated to remove trace ethyl acetate, and recycled for
subsequent reactions.
1-Methyl-3-[(1-methyl-1H-indol-3-yl) (3-Phenyl-
1H-pyrazol-4-yl)methyl]-1H-indole3e
Brown solid, mp 142◦C. νmax (KBr)/cm−1 3432, 3059, 2926, 1616,
1473, 1329, 1097, 1013, 740. δH ([D6]DMSO) 12.84 (1H, br s, pyrazole
NH), 7.55 (2H, d, J 8.4), 7.35 (2H, d, J 8.5), 7.33 (3H, d, J 3.9), 7.31
(1H, s), 7.18 (2H, d, J 7.6), 7.05 (2H, t, J 7.6), 6.85 (2H, t, J 7.6), 6.83
(2H, s), 5.80 (1H, s), 3.64 (6H, s). δC ([D6]DMSO) 164.2, 149.4, 137.6,
132.2, 129.4, 129.1, 128.3, 127.1, 122.1, 121.5, 119.5, 118.9, 118.2,
116.5, 110.2, 32.8, 29.9. m/z 416 (M+). (Found: C 80.72, H 5.78, N
13.44. C28H24N4 requires C 80.74, H 5.81, N 13.45%.)
1-Methyl-3-[(1-methyl-1H-indol-3-yl) (3-(4-Chlorophenyl)-
1H-pyrazol-4-yl)methyl]-1H-indole3f
3-[1H-Indol-3-yl(3-phenyl-1H-pyrazol-4-yl)methyl]-1H-indole 3a
Light orange solid, mp 205–206◦C. νmax (KBr)/cm−1 3410, 3048,
1627, 1462, 1420, 1339, 1095, 745. δH ([D6]DMSO) 12.52 (1H, br s,
pyrazole NH), 10.78 (2H, s, indole NH), 7.56 (2H, d, J 7.6), 7.44 (1H, s),
7.35–7.27 (5H, m), 7.17 (2H, d, J 7.6), 6.99 (2H, t, J 7.6), 6.86 (2H, s),
6.81 (2H, t, J 7.7), 5.83 (1H, s). δC ([D6]DMSO) 170.9, 137.2, 134.3,
132.4, 129.2, 127.9, 126.8, 123.9, 121.4, 119.3, 118.8, 114.3, 112.1,
111.2, 56.6, 30.2. m/z 388 (M+). (Found: C 80.38, H 5.16, N 14.40.
C26H20N4 requires C 80.39, H 5.19, N 14.42%.)
Pale orange solid, mp 138◦C. νmax (KBr)/cm−1 3431, 3056, 2928,
1617, 1470, 1326, 1097, 745. δH ([D6]DMSO) 12.85 (1H, br s, pyrazole
NH), 7.54 (2H, d, J 8.4), 7.35 (2H, d, J 8.5), 7.33 (2H, d, J 7.6), 7.31
(1H, s), 7.18 (2H, d, J 8.5), 7.05 (2H, t, J 7.7), 6.85 (2H, t, J 7.6),
6.82 (2H, s), 5.79 (1H, s), 3.64 (6H, s). δC ([D6]DMSO) 161.5, 152.1,
129.4, 129.1, 128.3, 127.1, 122.1, 121.5, 119.5, 118.9, 118.2, 117.1,
115.2, 111.1, 110.2, 89.7, 32.1. m/z 450 (M+). (Found: C 74.56, H 5.11,
N 12.39. C28H23ClN4 requires C 74.57, H 5.14, N 12.42%.)
3-[1H-Indol-3-yl(3-(4-chlorophenyl)-1H-pyrazol-4-yl)methyl]-
1H-indole3b
1-Methyl-3-[(1-methyl-1H-indol-3-yl) (3-(3-Methoxyphenyl)-
1H-pyrazol-4-yl)methyl]-1H-indole3g
Orange solid, mp 226–228◦C. νmax (KBr)/cm−1 3417, 1623, 1454,
1416, 1099, 737. δH ([D6]DMSO) 12.85 (1H, br s, pyrazole NH), 10.80
(2H, s, indole NH), 7.61 (2H, d, J 8.2), 7.39 (3H, t, J 7.6), 7.35 (1H, t,
J 7.6), 7.34 (1H, s), 7.22 (2H, d, J 8.0), 7.03 (2H, t, J 7.7), 6.88 (2H, s),
6.85 (2H, t, J 7.6), 5.86 (1H, s). δC ([D6]DMSO) 160.1, 137.2, 134.4,
128.7, 126.6, 126.2, 124.0, 121.1, 119.5, 118.5, 116.6, 116.1, 115.9,
111.8, 109.2, 33.5. m/z 422 (M+). (Found: C 73.80, H 4.53, N 13.19.
C26H19ClN4 requires C 73.84, H 4.53, N 13.25%.)
Pale orange solid, mp 172–174◦C. νmax (KBr)/cm−1 3430, 2923,
1454, 1416, 1037, 742. δH ([D6]DMSO) 12.85 (1H, br s, pyrazole NH),
7.48 (2H, d, J 8.4), 7.39 (1H, s), 7.36 (3H, t, J 6.1), 7.34 (1H, s), 7.26
(2H, t, J 6.9), 7.04 (2H, t, J 6.9), 6.73 (2H, d, J 8.4), 6.68 (2H, s),
5.95 (1H, s), 3.70 (6H, s). δC ([D6]DMSO) 171.5, 159.4, 143.7, 137.7,
136.0, 129.2, 128.2, 127.3, 124.4, 121.5, 120.2, 118.8, 118.7, 114.2,
109.2, 60.6, 55.3, 32.8, 29.9. m/z 446 (M+). (Found: C 78.02, H 5.83,
N 12.49. C29H26N4O requires C 78.00, H 5.87, N 12.55%.)
3-[1H-Indol-3-yl(3-(3-methoxyphenyl)-1H-pyrazol-4-yl)methyl]-
1H-indole3c
1-Propyl-3-[(1-propyl-1H-indol-3-yl) (3-Phenyl-
1H-pyrazol-4-yl)methyl]-1H-indole 3h
Orange solid, mp 202–204◦C. νmax (KBr)/cm−1 3418, 3037, 1620,
1462, 1431, 1250, 1088, 1037, 745. δH ([D6]DMSO) 12.80 (1H, br s,
pyrazole NH), 10.76 (2H, s, indole NH), 7.31 (2H, d, J 8.4), 7.27 (1H, s),
7.24–7.17 (4H, m), 7.03 (1H, s, Ph), 7.00 (3H, t, J 7.7), 6.85 (2H, s), 6.81
(2H, t, J 7.6), 5.83 (1H, s), 3.37 (3H, s). δC ([D6]DMSO) 159.7, 137.2,
130.1, 129.4, 126.9, 125.3, 123.9, 122.0, 121.4, 119.9, 119.4, 119.1,
118.7, 116.2, 114.0, 112.6, 112.0, 55.0, 30.4. m/z 418 (M+). (Found:
Pale brown solid, mp 208–210◦C. νmax (KBr)/cm−1 3415, 3032,
1620, 1430, 1088, 1035, 745. δH ([D6]DMSO) 12.82 (1H, br s, pyrazole
NH), 7.56 (2H, d, J 7.6), 7.35–7.32 (5H, m), 7.28 (1H, s), 7.24 (2H,
t, J 7.7), 7.19 (2H, t, J 7.7), 6.97 (2H, t, J 7.7), 6.68 (2H, s), 5.94
(1H, s), 4.01–3.97 (4H, m), 1.83–1.73 (4H, m), 0.85 (6H, t, J 6.9). δC
([D6]DMSO) 144.3, 137.0, 131.9, 128.7, 127.9, 127.8, 127.4, 127.3,
122.1, 121.3, 120.3, 118.6, 118.2, 109.4, 47.9, 30.1, 27.1, 23.6, 11.6.