S. Fuse, T. Takahashi, et al.
FULL PAPER
ppm. 13C NMR (100 MHz, CDCl3): δ = 158.3, 150.0, 144.0, 133.6,
132.5, 131.6, 130.3, 129.8, 128.6, 128.3, 127.8, 126.5, 121.1, 120.5,
The residue was dissolved in CH2Cl2, and DDQ was added at room
temperature under an argon atmosphere. The mixture was stirred
at room temperature for 1 h, then it was poured into saturated
aqueous NaHCO3. The aqueous layer was extracted with ethyl
acetate (2ϫ). The combined extracts were washed with brine, dried
with Na2SO4, and concentrated in vacuo. The residue was purified
to give the 1,3,5-triarylpyrazole.
114.5, 55.5, 28.6, 15.4 ppm. IR (KBr): ν = 2965, 1548, 1516, 1248,
˜
833 cm–1. HRMS (ESI-TOF): calcd. for C24H22ClN2O [M + H]+
389.1421; found 389.1389.
1,3-Bis(4-chlorophenyl)-4-(4-tolyl)-1H-pyrazole (13e): Purified by
chromatography on silica gel (hexane/toluene, 1:1); yield 47 %;
white solid; m.p. 137–139 °C. 1H NMR (400 MHz, CDCl3): δ =
7.92 (s, 1 H), 7.71 (d, J = 8.8 Hz, 2 H), 7.52 (d, J = 8.8 Hz, 2 H),
1,5-Bis(4-chlorophenyl)-3-(4-ethylphenyl)-1H-pyrazole (14b): DDQ
(2.00 equiv.); purified by chromatography on silica gel (hexane/
7.43 (d, J = 8.8 Hz, 2 H), 7.29 (d, J = 8.8 Hz, 2 H), 7.20 (d, J = ethyl acetate, 3:1); yield 61%; yellow solid; m.p. 139–141 °C. 1H
8.3 Hz, 2 H), 7.15 (d, J = 8.3 Hz, 2 H), 2.38 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 149.5, 138.4, 137.1, 133.9, 131.9,
131.5, 129.6, 129.5, 129.4, 129.3, 128.6, 128.5, 126.5, 123.3, 120.0,
NMR (400 MHz, CDCl3): δ = 7.80 (d, J = 8.3 Hz, 2 H), 7.29–7.36
(m, 8 H), 7.20 (d, J = 8.8 Hz, 2 H), 6.77 (s, 1 H), 2.69 (q, J =
7.8 Hz, 2 H), 1.27 (t, J = 7.8 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 152.5, 144.5, 143.1, 138.5, 134.6, 133.2, 130.1, 130.0,
21.2 ppm. IR (KBr): ν = 2922, 1597, 1554, 1495, 1218, 1093, 827,
˜
734, 505 cm–1. HRMS (ESI-TOF): calcd. for C22H17Cl2N2 [M + 129.2, 128.9, 128.9, 128.2, 126.3, 125.8, 105.6, 28.7, 15.5 ppm. IR
H]+ 379.0769; found 379.0741.
(KBr): ν = 2964, 2930, 1496, 1093, 832, 797, 501 cm–1. HRMS
˜
(ESI-TOF): calcd. for C23H19Cl2N2 [M + H]+ 393.0925; found
393.0887.
1,3,4-Tris(4-chlorophenyl)-1H-pyrazole (13f): Purified by GPC;
yield 19 %; yellow solid; m.p. 139–140 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.92 (s, 1 H), 7.69 (d, J = 8.8 Hz, 2 H), 7.48 (d, J = 3-(4-Ethylphenyl)-1-(4-methoxyphenyl)-5-(4-tolyl)-1H-pyrazole
8.8 Hz, 2 H), 7.42 (d, J = 8.8 Hz, 2 H), 7.27–7.34 (m, 4 H), 7.18 (14c): DDQ (1.10 equiv.); purified by chromatography on silica gel
(d, J = 8.8 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 149.5, (toluene); yield 42 %; brown solid; m.p. 168–170 °C. 1H NMR
138.2, 134.2, 133.2, 132.2, 131.1, 130.8, 129.9, 129.6, 128.9, 128.7,
(400 MHz, CDCl3): δ = 7.82 (d, J = 8.3 Hz, 2 H), 7.28 (d, J =
9.3 Hz, 2 H), 7.25 (d, J = 8.3 Hz, 2 H), 7.16 (d, J = 8.3 Hz, 2 H),
7.11 (d, J = 8.3 Hz, 2 H), 6.86 (d, J = 9.3 Hz, 2 H), 6.74 (s, 1 H),
3.81 (s, 3 H), 2.68 (q, J = 7.8 Hz, 2 H), 1.26 (t, J = 7.8 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 158.7, 151.7, 144.3, 143.9,
138.0, 133.7, 130.7, 129.1, 128.5, 128.1, 127.8, 126.7, 125.8, 114.1,
126.6, 122.1, 120.0 ppm. IR (KBr): ν = 2927, 1704, 1596, 1489,
˜
1093, 1014, 831, 501 cm–1. HRMS (ESI-TOF): calcd. for
C21H14Cl3N2 [M + H]+ 399.0223; found 399.0187.
3-(4-Chlorophenyl)-1-(4-methoxyphenyl)-4-(4-tolyl)-1H-pyrazole
(13g): Purified by chromatography on silica gel (toluene); yield
104.3, 55.5, 28.7, 21.2, 15.5 ppm. IR (KBr): ν = 2963, 2931, 1515,
˜
1
83%; white solid; m.p. 122–123 °C. H NMR (400 MHz, CDCl3):
1250, 833, 794, 588 cm–1 . HRMS (ESI-TOF): calcd. for
C25H25N2O [M + H]+ 369.1967; found 369.1928.
δ = 7.86 (s, 1 H), 7.66 (d, J = 8.8 Hz, 2 H), 7.53 (d, J = 8.8 Hz, 2
H), 7.28 (d, J = 8.8 Hz, 2 H), 7.21 (d, J = 8.3 Hz, 2 H), 7.14 (d, J
= 8.3 Hz, 2 H), 6.98 (d, J = 8.8 Hz, 2 H) ppm. 13C NMR 5-(4-Chlorophenyl)-3-(4-ethylphenyl)-1-(4-methoxyphenyl)-1H-pyr-
(100 MHz, CDCl3): δ = 158.3, 148.7, 136.7, 133.6, 133.5, 131.9, azole (14d): DDQ (2.00 equiv.); purified by chromatography on sil-
129.7, 129.6, 129.3, 128.6, 128.4, 126.8, 122.5, 120.6, 114.5, 55.5,
ica gel (hexane/ethyl acetate, 3:1); yield 68 %; brown solid; m.p.
191–192 °C. H NMR (400 MHz, CDCl3): δ = 7.81 (d, J = 8.3 Hz,
1
21.1 ppm. IR (KBr): ν = 2935, 1574, 1553, 1520, 1508, 1253, 828,
˜
801, 733, 654, 589, 516 cm–1. HRMS (ESI-TOF): calcd. for
C23H20ClN2O [M + H]+ 375.1264; found 375.1238.
2 H), 7.29 (d, J = 8.8 Hz, 2 H), 7.23–7.29 (m, 4 H), 7.20 (d, J =
8.8 Hz, 2 H), 6.88 (d, J = 9.3 Hz, 2 H), 6.76 (s, 1 H), 3.83 (s, 3 H),
2.69 (q, J = 7.8 Hz, 2 H), 1.27 (t, J = 7.8 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 159.0, 151.8, 144.1, 143.0, 134.2, 133.2,
130.4, 129.9, 129.1, 128.7, 128.1, 126.8, 125.7, 114.2, 104.6, 55.5,
3,4-Bis(4-chlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazole (13h):
Purified by chromatography on silica gel (hexane/toluene, 1:3);
yield 60 %; grey solid; m.p. 156–157 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.86 (s, 1 H), 7.64 (d, J = 9.3 Hz, 2 H), 7.48 (d, J =
8.3 Hz, 2 H), 7.29 (d, J = 8.3 Hz, 2 H), 7.22 (d, J = 8.3 Hz, 2 H),
6.97 (d, J = 9.3 Hz, 2 H), 3.83 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 158.5, 148.7, 133.8, 133.4, 132.9, 131.5, 131.2, 129.9,
129.6, 128.8, 128.6, 126.8, 121.3, 120.7, 114.6, 55.5 ppm. IR (KBr):
28.7, 15.5 ppm. IR (KBr): ν = 2965, 2928, 1513, 1250, 835,
˜
722 cm–1. HRMS (ESI-TOF): calcd. for C24H22ClN2O [M + H]+
389.1421; found 389.1385.
1,3-Bis(4-chlorophenyl)-5-(4-tolyl)-1H-pyrazole (14e): DDQ
(1.10 equiv.); purified by chromatography on silica gel (hexane/tol-
uene, 1:1); yield 55 %; brown solid; m.p. 191–192 °C. 1H NMR
ν = 2936, 2836, 1573, 1547, 1519, 1487, 1252, 1094, 832, 733, 642,
˜
502 cm–1. HRMS (ESI-TOF): calcd. for C22H17Cl2N2O [M + H]+ (400 MHz, CDCl3): δ = 7.82 (d, J = 8.3 Hz, 2 H), 7.37 (d, J =
395.0718; found 395.0701.
8.3 Hz, 2 H), 7.29 (br. s, 4 H), 7.13 (br. s, 4 H), 6.72 (s, 1 H), 2.35
(s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.0, 144.7,
138.7, 138.6, 133.8, 133.0, 131.4, 129.3, 129.0, 128.8, 128.6, 127.2,
General Stepwise Procedure for Three-Component Coupling and
Subsequent Oxidation Using DDQ for the Synthesis of 1,3,5-Triar-
ylpyrazoles: Hydrazine (2.00 equiv.) was added to a stirred solution
of aldehyde (2.00 equiv.) in dry THF (3.00 mL/equiv.) at room tem-
perature under an argon atmosphere. The mixture was stirred at
the same temperature for 1 h, then tBuOK (2.50 equiv.) was added
at –78 °C. The mixture was stirred at the same temperature for
30 min, then phenylsulfonyl alkene (1.00 equiv.) was added at
–78 °C. The mixture was stirred at 50 °C for 3 h, then TFA
(5.00 equiv.) was added at –78 °C. The mixture was stirred at room
temperature for 24 h, then it was poured into saturated aqueous
NaHCO3. The aqueous layer was extracted with ethyl acetate (2ϫ).
The combined extracts were washed with brine, dried with Na2SO4,
and concentrated in vacuo. The residue was used in the next reac-
tion without further purification.
127.0, 126.2, 105.2, 21.2 ppm. IR (KBr): ν = 2923, 1495, 1435,
˜
1357, 1091, 833, 794, 504 cm–1. HRMS (ESI-TOF): calcd. for
C22H17Cl2N2 [M + H]+ 379.0769; found 379.0745.
1,3,5-Tris(4-chlorophenyl)-1H-pyrazole (14f): DDQ (2.00 equiv.);
purified by chromatography on silica gel (hexane/toluene, 1:3);
yield 69%; red-brown solid; m.p. 142–144 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.82 (d, J = 8.3 Hz, 2 H), 7.40 (d, J = 8.3 Hz, 2 H),
7.03–7.36 (m, 4 H), 7.27 (d, J = 8.8 Hz, 2 H), 7.19 (d, J = 8.8 Hz,
2 H), 6.77 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 151.3,
143.4, 138.3, 134.8, 134.0, 133.5, 131.2, 129.9, 129.2, 129.0, 128.9,
128.5, 127.0, 126.3, 105.5 ppm. IR (KBr): ν = 1596, 1496, 1483,
˜
1436, 1357, 1094, 1015, 971, 833, 798, 505 cm–1. HRMS (ESI-
TOF): calcd. for C21H14Cl3N2 [M + H]+ 399.0223; found 399.0191.
4762
www.eurjoc.org
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4756–4764