5-Amino-3-tert-butyl-1-methyl-1H-pyrazole (3d). Compound
3d (0.55 g, 91%) was prepared according to the given procedure us-
ing methylhydrazine (1a) (0.21 mL, 3.9 mmol) and was obtained as
a colourless solid, mp 156–157 ◦C (light petroleum) (Found: MH+,
154.1340. C8H16N3 [MH+] requires 154.1339); mmax(KBr)/cm−1
2964, 1628, 1560, 1418, 1382, 1360, 1255; dH(400 MHz; CDCl3)
5.34 (1H, s, 4-H), 3.56 (3H, s, Me), 3.47 (2H, br s, NH2), 1.20
(9H, s, CMe3); dC(125 MHz; CDCl3) 160.6 (C), 144.5 (C), 87.5
(CH), 34.0 (Me), 32.0 (C), 30.9 (Me); m/z 154 (MH+, 100%).
5-Amino-3-phenyl-1-methyl-1H-pyrazole (3h). Compound 3h
(0.60 g, 89%) was prepared according to the given procedure using
methylhydrazine (1a) (0.21 mL, 3.9 mmol) and benzoylacetonitrile
(2b) (0.58 g, ◦4.0 mmol) and was obtained as an off-white solid,
mp 128–130 C (EtOAc) (lit.,22 129 ◦C) (Found: MH+, 174.1023.
C10H12N3 [MH+] requires 174.1026); mmax(KBr)/cm−1 3420, 3151,
1623, 1562, 1511, 1446, 1373, 1270, 1025, 959, 908; dH(400 MHz;
CDCl3) 7.75 (2H, m, 2ꢀ,6ꢀ-H), 7.39 (2H, m, 3ꢀ,5ꢀ-H), 7.29 (1H, m,
4ꢀ-H), 5.88 (1H, s, 4-H), 3.73 (3H, s, Me), 3.48 (2H, br s, NH2);
dC(125 MHz; CDCl3) 149.7 (C), 145.6 (C), 133.9 (C), 128.5 (CH),
127.5 (CH), 125.3 (CH), 88.6 (CH), 34.4 (Me); m/z 174 (MH+,
100%).
5-Amino-1,3-diphenyl-1H-pyrazole (3e). Compound 3e (0.75 g,
80%) was prepared according to the given procedure using
phenylhydrazine (1a) (0.39 mL, 4.0 mmol) and benzoylacetonitrile
(2b) (0.58 g, 4◦.0 mmol) and was obtained as a light brown solid,
mp 128–129 C (light petroleum–EtOAc) (lit.,20 129–130 ◦C)
(Found: MH+, 236.1183. C15H14N3 [MH+] requires 236.1182);
mmax(KBr)/cm−1 3308, 3208, 3046, 1633, 1596, 1560, 1503, 1463,
1375, 1068, 950, 918, 751; dH(400 MHz; CDCl3) 7.74 (2H, m, 2,6-
PhH), 7.56 (2H, m, N-2,6-PhH), 7.42 (2H, m, N-3,5-PhH), 7.31
(2H, m, 3,5-PhH), 7.28 (1H, m, N-4-PhH), 7.23 (1H, m, 4-PhH),
5.76 (1H, s, 4-H); dC(125 MHz; CDCl3) 151.5 (C), 145.9 (C), 138.7
(C), 133.5 (C), 129.5 (CH), 128.5 (CH), 127.8 (CH), 127.5 (CH),
125.7 (CH), 124.2 (CH), 88.2 (CH); m/z (ES) 236 (MH+, 100%).
5-Amino-3-phenyl-1-tert-butyl-1H-pyrazole
hydrochloride
(3i·HCl). Compound 3i·HCl (0.94 g, 94%) was prepared
according to the given procedure using tert-butylhydrazine
hydrochloride (1e·HCl) (0.50 g, 4.0 mmol) and benzoylacetonitrile
(2b) (0.58 g, 4.0 mmol) and was obtained as an orange oil (Found:
MH+, 216.1496. C13H18N3 [MH+] requires 216.1495); dH(400 MHz;
CDCl3) 7.92 (2H, m, 2ꢀ,6ꢀ-H), 7.66 (1H, m, 4ꢀ-H), 7.52 (2H, m,
3ꢀ,5ꢀ-H), 6.28 (1H, s, 4-H), 1.47 (9H, s, CMe3); dC(125 MHz;
CDCl3) 152.4 (C), 149.8 (C), 130.8 (C), 129.2 (CH), 128.7 (CH),
127.9 (CH), 93.5 (CH), 31.42 (C), 28.7 (Me); m/z 216 (MH+,
100%), 160 (95), 129 (43).
5-Amino-1,3-diphenyl-1H-pyrazole hydrochloride (3e·HCl).
Compound 3e·HCl (0.95 g, 88%) was prepared according to the
given procedure using phenylhydrazine hydrochloride (1a·HCl)
(0.58 g, 4.0 mmol) and benzoylacetonitrile (2b) (0.58 g, 4.0 mmol)
1-(3-tert-Butyl-1-phenyl-1H-pyrazol-5-yl)-3-phenylurea (4a)
Phenyl isocyanate (0.33 mL, 3.0 mmol) was added to a stirred
solution of 5-aminopyrazole 1a (0.65 g, 3.0 mmol) in CH2Cl2
(6 mL). The mixture was stirred for 20 min and evaporated in vacuo.
After triturating with EtOAc–light petroleum (1 : 1), purification
by recrystallization (MeOH) gave the◦title compound (0.93 g, 93%)
as colourless crystals, mp 197–200 C (MeOH) (lit.,8c 211 ◦C)
(Found C, 71.7; H, 6.65; N, 16.6. Calc. for C20H22N4O: C, 71.8;
H, 6.65; N, 16.8%) (Found: MH+, 335.1863. C20H23N4O [MH+]
requires 335.1866); mmax(KBr)/cm−1 3380, 3278, 3141, 3082, 2957,
2865, 1665, 1599, 1550, 1500, 1449, 1372, 1312, 1224; dH(400 MHz;
CD3OD) 7.61–7.48 (5H, PhH), 7.37 (2H, m, N-2,6-PhH), 7.28
(2H, m, N-3,5-PhH), 7.04 (1H, m, N-4-PhH), 6.68 (1H, s, 4ꢀ-H),
1.36 (9H, s, CMe3); dC(100 MHz; CD3OD) 162.3 (C), 152.7 (C),
138.6 (C), 138.0 (C), 137.5 (C), 129.2 (CH), 128.5 (CH), 128.2
(CH), 125.6 (CH), 122.8 (CH), 118.9 (CH), 95.1 (CH), 31.9 (C),
29.4 (Me); m/z 335 (MH+, 100%), 216 (47).
◦
and was obtained as a colourless solid, mp 145–147 C (EtOAc)
(Found: MH+, 236.1185. C15H14N3 [MH+] requires 236.1182);
mmax(KBr)/cm−1 3246, 3100, 1634, 1574, 1510, 1289, 1103, 946,
918; dH(400 MHz; CDCl3) 7.89 (2H, m, 2,6-PhH), 7.58 (2H, m,
N-2,6-PhH), 7.53 (2H, m, N-3,5-PhH), 7.47 (2H, m, 3,5-PhH),
7.41 (1H, m, N-4-PhH), 7.39 (1H, m, 4-PhH), 6.09 (1H, s, 4-H);
dC(125 MHz; CDCl3) 150.6 (C), 149.1 (C), 140.9 (C), 137.8 (C),
134.7 (CH), 130.7 (CH), 129.4 (CH), 128.9 (CH), 127.4 (CH),
125.6 (CH), 89.5 (CH); m/z (ES) 236 (MH+, 100%).
5-Amino-3-phenyl-1-p-tolyl-1H-pyrazole21
hydrochloride
(3f·HCl). Compound 3f·HCl (0.81 g, 74%) was prepared
according to the given procedure using benzoylacetonitrile (2b)
(0.58 g◦, 4.0 mmol) and was obtained as a brown solid, mp
66–67 C (Found: MH+, 250.1340. C16H16N3 [MH+] requires
250.1344); mmax(KBr)/cm−1 3283, 3150, 1650, 1635, 1620, 1558,
1515, 1459, 1374, 1312, 1281, 1025, 814, 758; dH(400 MHz;
CD3OD) 7.78 (2H, m, 2,6-PhH), 7.54–7.43 (8H), 2.47 (3H, s,
Me); dC(125 MHz; CDCl3) 150.8 (C), 150.3 (C), 140.3 (C), 134.1
(C), 132.2 (C), 130.4 (CH), 129.9 (CH), 128.8 (CH), 126.1 (CH),
125.5 (CH), 87.8 (CH), 19.9 (Me); m/z 250 (MH+, 100%).
5-(2,2,2-Trichloroethoxycarbonyl)amino-3-tert-butyl-1-p-tolyl-
1H-pyrazole (4b)
A mixture of 5-amino-3-tert-butyl-1-p-tolylpyrazole hydrochlo-
ride (3b·HCl) (3.0 g, 11.3 mmol), water (15 mL), EtOAc (30 mL)
and NaOH (1.14 g, 28.5 mmol) was stirred at 0 ◦C for 30 min.
2,2,2-Trichloroethyl chloroformate (3.89 g, 18.4 mmol) was added
over a period of 1 h at this temperature and then the mixture
was stirred at RT for 2 h. The organic layer was decanted
and the aqueous layer further extracted with EtOAc (2 ×
20 ml). The combined organic layers were washed with brine
(20 mL), dried (Na2SO4) and evaporated in vacuo to give the
title◦ compound (2.41 g, 47%) as a colourless solid, mp 151–
153 C (heptane) (Found: MH+, 404.0694. C17H2135Cl3N3O2 [MH+]
requires 404.0694); mmax(KBr)/cm−1 3126, 2964, 1749, 1598, 1521,
1464, 1364, 1228; dH(400 MHz; CDCl3) 7.36 (2H, d, J 8.3, 2ꢀ,6ꢀ-H),
5-Amino-3-phenyl-1H-pyrazole (3g). Compound 3g (0.75 g,
80%) was prepared according to the given procedure using
hydrazine monohydrate (1c·H2O) (0.20 mL, 4.1 mmol) and
benzoylacetonitrile (2b) (0.58◦g, 4.0 mmol) and was obtained as a
light brown solid, mp 94–95 C (light petroleum) (Found: MH+,
160.0868. C9H10N3 [MH+] requires 160.0869); mmax(KBr)/cm−1
3171, 1651, 1516, 1102, 1072, 1008, 956; dH(400 MHz; CD3OD)
7.65 (2H, d, J 7.5, 2ꢀ,6ꢀ-H), 7.40 (2H, m, 3ꢀ,5ꢀ-H), 7.33 (1H, m,
4ꢀ-H), 5.95 (1H, s, 4-H); dC(125 MHz; CD3OD) 154.3 (C), 145.7
(C), 130.3 (C), 128.9 (CH), 128.3 (CH), 125.4 (CH), 90.4 (CH);
m/z 160 (MH+, 100%).
4162 | Org. Biomol. Chem., 2006, 4, 4158–4164
This journal is
The Royal Society of Chemistry 2006
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