H. Zhu et al.
FULL PAPER
4-Chloro-3-ethoxy-5-(p-tolyl)-1H-pyrazole (8o): White solid; m.p.
107–108 °C. H NMR (500 MHz, [D6]DMSO): δ = 12.51 (s, 1 H,
NH), 7.62 (d, J = 8.0 Hz, 2 H, ArH), 7.32 (d, J = 8.0 Hz, 2 H,
(300 MHz, CDCl3): δ = 7.32–7.10 (m, 9 H, ArH), 4.99 (s, 2 H,
CH2) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 169.4, 157.5,
138.8, 138.6, 133.2, 130.6, 129.5, 129.4, 129.2, 129.1, 128.3, 127.6,
1
ArH), 4.25 (q, J = 7.0 Hz, 2 H, CH2), 2.35 (s, 3 H, CH3), 1.34 (t, 124.7, 95.5, 65.0 ppm. IR (neat): ν = 3412, 2923, 2855, 2663, 2576,
˜
J = 7.0 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 1740, 1593, 1555, 1512, 1442, 1408, 1375, 1256, 1139, 893, 792, 760,
158.4, 138.4, 138.2, 129.4, 126.2, 125.2, 90.5, 64.3, 20.8, 14.7 ppm.
726, 688 cm–1. C17H12Cl2N2O3 (363.20): calcd. C 56.22, H 3.33, N
7.71; found C 56.33, H 3.34, N 7.68.
IR (neat): ν = 3132, 3040, 2928, 1588, 1527, 1472, 1385, 1355, 1305,
˜
1119, 1036, 963, 899, 820, 761, 718, 637 cm–1. C12H13ClN2O
(236.70): calcd. C 60.89, H 5.54, N 11.84; found C 60.78, H 5.53,
N 11.81.
2-(4-Chloro-1,5-diphenyl-1H-pyrazol-3-yloxy)-1-(2-thioxothiazol-
idin-3-yl)ethanone (8v): Yellow solid; m.p. 175–176 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.36–7.13 (m, 10 H, ArH), 5.79 (s, 2 H,
CH2), 4.61 (t, J = 7.6 Hz, 2 H, CH2), 3.39 (t, J = 7.6 Hz, 2 H,
CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.3, 169.7, 158.1,
140.3, 139.8, 129.8, 129.1, 128.8, 128.6, 128.5, 127.0, 124.6, 115.0,
Ethyl 2-(4-Chloro-1,5-diphenyl-1H-pyrazol-3-yloxy)acetate (8p):
Yellow solid; m.p. 59–60 °C. 1H NMR (500 MHz, CDCl3): δ =
7.37–7.34 (m, 3 H, ArH), 7.29–7.27 (m, 2 H, ArH), 7.26–7.24 (m,
2 H, ArH), 7.23–7.18 (m, 1 H, ArH), 7.15–7.13 (m, 2 H, ArH),
4.92 (s, 2 H, CH2), 4.28 (q, J = 7.2 Hz, 2 H, CH2), 1.30 (t, J =
7.2 Hz, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.4,
158.0, 140.1, 139.6, 129.7, 129.0, 128.7, 128.5, 128.2, 126.8, 124.3,
70.0, 55.6, 29.8 ppm. IR (neat): ν = 3409, 3063, 2948, 1711, 1595,
˜
1551, 1514, 1493, 1364, 1279, 1230, 1186, 1130, 767, 697 cm–1
.
C20H16ClN3O2S2 (429.94): calcd. C 55.87, H 3.75, N 9.77; found C
55.75, H 3.76, N 9.74.
96.7, 65.5, 61.2, 14.1 ppm. IR (neat): ν = 3061, 2989, 1762, 1596,
˜
2-[4-Chloro-5-(3-chlorophenyl)-1-phenyl-1H-pyrazol-3-yloxy]-1-
(2-thioxothiazolidin-3-yl)ethanone (8w): Yellow solid; m.p. 168–
169 °C. H NMR (500 MHz, [D6]DMSO): δ = 7.52–7.18 (m, 9 H,
ArH), 5.75 (s, 2 H, CH2), 4.55 (t, J = 7.5 Hz, 2 H, CH2), 3.49 (t,
J = 7.5 Hz, 2 H, CH2) ppm. 13C NMR (125 MHz, CDCl3): δ =
202.4, 168.5, 157.3, 138.8, 138.7, 133.2, 130.5, 129.4, 129.3, 129.2,
1551, 1519, 1445, 1407, 1379, 1291, 1210, 1141, 1093, 1063, 1024,
959, 762, 698, 648 cm–1. C19H17ClN2O3 (356.81): calcd. C 63.96, H
4.80, N 7.85; found C 63.85, H 4.81, N 7.82.
1
Ethyl 2-[4-Chloro-1-phenyl-5-(p-tolyl)-1H-pyrazol-3-yloxy]acetate
(8q): White solid; m.p. 72–73 °C. 1H NMR (300 MHz, CDCl3): δ
= 7.26–7.14 (m, 9 H, ArH), 4.92 (s, 2 H, CH2), 4.28 (q, J = 7.1 Hz,
2H CH2), 2.36 (s, 3 H, CH3), 1.30 (t, J = 7.1 Hz, 3 H, CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 168.5, 158.0, 140.3, 139.1, 129.6,
129.5, 129.2, 128.7, 126.8, 125.3, 124.4, 115.7, 65.5, 61.2, 21.4,
129.1, 128.9, 128.3, 127.6, 124.8, 69.3, 55.7, 29.6 ppm. IR (neat): ν
˜
= 3405, 2952, 1715, 1594, 1550, 1513, 1445, 1364, 1278, 1230, 1188,
1132, 1095, 1053, 975, 879, 793, 769, 707, 674, 649 cm–1
.
C20H15Cl2N3O2S2 (464.38): calcd. C 51.73, H 3.26, N 9.05; found
C 51.62, H 3.27, N 9.08.
14.2 ppm. IR (neat): ν = 2982, 2929, 1760, 1596, 1524, 1496, 1445,
˜
1408, 1380, 1295, 1209, 1139, 1092, 1051, 1019, 961, 821, 770, 721,
695, 653 cm–1. C20H19ClN2O3 (370.83): calcd. C 64.78, H 5.16, N
7.55; found C 64.66, H 5.18, N 7.52.
2-[4-Chloro-5-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-3-yloxy]-1-
(2-thioxothiazolidin-3-yl)ethanone (8x): Yellow solid; m.p. 193–
194 °C. 1H NMR (500 MHz, CDCl3): δ = 7.26–7.15 (m, 7 H, ArH),
6.88 (d, J = 8.8 Hz, 2 H, ArH), 5.78 (s, 2 H, CH2), 4.61 (t, J =
7.6 Hz, 2 H, CH2), 3.82 (s, 3 H, OCH3), 3.38 (t, J = 7.6 Hz, 2 H,
CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.2, 169.7, 160.1,
158.0, 140.1, 139.8, 131.1, 128.7, 126.8, 125.4, 124.5, 120.5, 114.0,
Ethyl 2-[4-Chloro-5-(3-chlorophenyl)-1-phenyl-1H-pyrazol-3-yloxy]-
acetate (8r): White solid; m.p. 88–89 °C. 1H NMR (300 MHz,
CDCl3): δ = 7.36–7.10 (m, 9 H, ArH), 4.92 (s, 2 H, CH2), 4.28 (q,
J = 7.1 Hz, 2 H, CH2), 1.30 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C
NMR (75 MHz, CDCl3): δ = 168.4, 159.9, 140.0, 139.3, 134.5,
131.0, 129.8, 129.6, 129.2, 128.8, 127.9, 126.6, 124.5, 114.0, 65.6,
69.9, 55.5, 55.3, 29.7 ppm. IR (neat): ν = 3406, 2940, 1714, 1615,
˜
1594, 1521, 1497, 1456, 1368, 1279, 1254, 1225, 1179, 1133, 1053,
1028, 879, 836, 773, 697, 652 cm–1. C21H18ClN3O3S2 (459.96):
calcd. C 54.84, H 3.94, N 9.14; found C 54.95, H 3.95, N 9.17.
61.2, 14.8 ppm. IR (neat): ν = 2957, 2856, 1764, 1725, 1596, 1547,
˜
1518, 1443, 1374, 1283, 1218, 1140, 1073, 979, 795, 765, 706 cm–1.
C19H16Cl2N2O3 (391.25): calcd. C 58.33, H 4.12, N 7.16; found C
58.25, H 4.13, N 7.18.
2-[4-Chloro-5-(4-chlorophenyl)-1-phenyl-1H-pyrazol-3-yloxy]-1-
(2-thioxothiazolidin-3-yl)ethanone (8y): Yellow solid; m.p. 192–
193 °C. 1H NMR (500 MHz, CDCl3): δ = 7.37–7.12 (m, 9 H, ArH),
5.79 (s, 2 H, CH2), 4.61 (t, J = 7.6 Hz, 2 H, CH2), 3.38 (t, J =
7.6 Hz, 2 H, CH2) ppm. 13C NMR (75 MHz, CDCl3): δ = 201.3,
169.6, 158.1, 139.5, 135.3, 131.7, 131.0, 128.9, 127.2, 126.7, 125.3,
2-(4-Chloro-1,5-diphenyl-1H-pyrazol-3-yloxy)acetic
Acid
(8s):
White solid; m.p. 183–184 °C. 1H NMR (300 MHz, [D6]DMSO): δ
= 13.03 (s, 1 H, OH), 7.45–7.13 (m, 10 H, ArH), 4.86 (s, 2 H, CH2)
ppm. 13C NMR (75 MHz, [D6]DMSO): δ = 169.5, 157.5, 140.1,
139.1, 129.5, 129.4, 129.0, 128.9, 128.7, 127.5, 127.3, 124.5,
124.6, 70.0, 55.5, 29.7 ppm. IR (neat): ν = 3405, 2938, 1712, 1593,
˜
64.9 ppm. IR (neat): ν = 3059, 2945, 2780, 2670, 2581, 1743, 1591,
˜
1546, 1515, 1444, 1367, 1277, 1222, 1188, 1133, 1090, 1050, 956,
878, 829, 768, 695, 646 cm–1. C20H15Cl2N3O2S2 (464.38): calcd. C
51.73, H 3.26, N 9.05; found C 51.58, H 3.27, N 9.08.
1554, 1520, 1444, 1406, 1376, 1320, 1255, 1140, 1093, 1055, 1029,
959, 900, 768, 722, 699, 643 cm–1. C17H13ClN2O3 (328.75): calcd.
C 62.11, H 3.99, N 8.52; found C 62.24, H 3.98, N 8.55.
General Procedure for the Synthesis of 4-Halo-3-oxypyrazoles 9a–f:
SOCl2 (5.0 mmol) was added to a round-bottom flask, and a solu-
tion of 3-oxypyrazole substrate 7 (1.0 mmol) in an organic solvent
(10 mL), and a catalytic amount of DMF (0.1 mmol) and KX
(15.0 mmol) were added (organic solvent for 9a–c: CHCl3, X = Br;
for 9d–f: cyclohexane, X = I). The mixture was heated to reflux
for 6 h (reaction monitored by HPLC), and then poured into H2O
(200 mL) with good stirring. After standing for 5 min, the organic
layer was separated and dried with anhydrous MgSO4. The solvent
was removed under reduced pressure, and the residue was purified
by flash column chromatography on silica gel (eluent for 9a–c: ethyl
2-[4-Chloro-1-phenyl-5-(p-tolyl)-1H-pyrazol-3-yloxy]acetic
Acid
(8t): White solid; m.p. 167–168 °C. 1H NMR (300 MHz, [D6]-
DMSO): δ = 13.14 (s, 1 H, OH), 7.37–7.14 (m, 9 H, ArH), 4.84 (s,
2 H, CH2), 2.32 (s, 3 H, CH3) ppm. 13C NMR (75 MHz, [D6]-
DMSO): δ = 169.5, 157.4, 140.1, 139.2, 139.0, 129.3, 129.0, 128.6,
127.3, 124.5, 64.9, 20.8 ppm. IR (neat): ν = 3031, 2922, 2661, 2575,
˜
1735, 1597, 1554, 1521, 1498, 1443, 1410, 1377, 1345, 1251, 1138,
1091, 1056, 1023, 959, 932, 824, 762, 724, 688, 646 cm–1.
C18H15ClN2O3 (342.78): calcd. C 63.07, H 4.41, N 8.17; found C
63.21, H 4.40, N 8.14.
2-[4-Chloro-5-(3-chlorophenyl)-1-phenyl-1H-pyrazol-3-yloxy]- acetate/petroleum ether, 1:6 v/v; for 9d–f: ethyl acetate/petroleum
acetic Acid (8u): White solid; m.p. 142–143 °C. 1H NMR
ether, 1:8 v/v) to afford the 4-halogenated product.
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Eur. J. Org. Chem. 2011, 5323–5330