R.-Y. Tang et al. / Journal of Fluorine Chemistry 127 (2006) 948–953
951
Table 2
Anal. calcd. for C14H11Cl2F3N4S: C, 42.55%, H, 2.81%;
found: C, 42.50%, H, 2.77%.
Synthesis of compounds 4a and 4c
Entry
Product
R
Melting point (8C)
Time (h)
Yield (%)a
3.2.4. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-butylthio-1H-pyrazole-3-carbonitrile (3e)
11
12
13
14
4a1
4a2
4c1
4c2
CF3
196–198
196–198
179–181
179–181
3
96
70
95
41
CF3
1
C2H5
C2H5
4
mp: 140–141 8C. IR (KBr): 3432, 3331, 3229, 2956, 2248,
1629, 1561, 1395, 1143, 887, 816 cmÀ1. NMR: 1H NMR
(300 MHz, C3D6O): d = 8.08 (s, 2H); 5.99 (s, 2H); 2.68 (t,
J = 7.02 Hz, 2H); 1.42–1.60 (m, 4H); 0.88 (t, J = 7.20 Hz, 3H).
13C NMR (75 MHz, C3D6O): d = 13.1 (1C), 21.2 (1C), 31.4
(1C), 35.3 (1C), 93.1 (1C), 122.4 (q, J = 271.0 Hz, 1C), 126.4
(4C), 132.1 (1C), 133.7 (q, J = 34.1, 1C), 136.5 (1C), 151.6
(1C). 19F NMR (220 MHz, C3D6O): d = À63.6 (s, 3F).
Anal. calcd. for C15H13Cl2F3N4S: C, 44.02%, H, 3.20%;
found: C, 43.90%, H, 3.11%.
0.5
4a eluted with hexane and ethyl acetate (5:1); 4a1, 4c1: oxidation by H2O2; 4a2,
4b2: oxidation by TCCA (trichloroisocyanuric acid); The melting point of 4a is
in agreement with the literature reported by Casado et al. [29].
a
Isolated yield based on compound 3.
phase was separated off, and turn back eluted by water (40 mL).
Finally dehydrated (MgSO4) and the volatile substances were
removed with a hard vacuum pump at its maximum output and
at a bath temperature of 80 8C to remove practically all the
DMF. The residue was subjected to a chromatography on a
column of silica gel, eluting with petroleum ether and ethyl
acetate (4:1), solution was removed under reduced pressure,
giving white-solid sulfides 3b–3j.
3.2.5. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-s-butylthio-1H-pyrazole-3-carbonitrile (3f)
mp: 142–144 8C. IR (KBr): 3430, 3329, 3227, 2963, 2249,
1628, 1558, 1395, 1141, 886, 808 cmÀ1. NMR: 1H NMR
(300 MHz, C3D6O): d = 8.08 (s, 2H); 5.97 (s, 2H); 2.89–2.96
(m, 1H); 1.50–1.66 (m, 2H), 1.25 (d, J = 6.75 Hz, 3H), 1.04
(t, J = 7.35 Hz, 3H). 13C NMR (75 MHz, C3D6O): d = 10.9
(1C), 19.8 (1C), 28.1 (1C), 46.4 (1C), 92.1 (1C), 113.2 (1C),
122.5 (q, J = 271.2 Hz, 1C), 126.4 (4C), 132.7 (1C), 133.7 (q,
J = 33.5 Hz, 1C), 136.5 (1C), 152.2 (1C). 19F NMR (220 MHz,
C3D6O): d = À63.6 (s, 3F).
3.2.1. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-methylthio-1H-pyrazole-3-carbonitrile (3b)
mp: 172–173 8C. IR (KBr): 3456, 3320, 3220, 2925, 2252,
1625, 1554, 1392, 1314, 1146, 876, 811 cmÀ1. NMR: 1H NMR
(300 MHz, C3D6O): d = 8.08 (s, 2H); 6.03 (s, 2H); 2.30 (s, 3H).
13C NMR (75 MHz, C3D6O): d = 18.9 (1C), 95.1 (1C), 122.5
(q, J = 271.1 Hz, 1C), 126.38 (2C), 126.42 (2C), 131.4 (1C),
133.7 (q, J = 34.0 Hz, 1C), 136.5 (1C), 151.2 (1C). 19F NMR
(220 MHz, C3D6O): d = À63.6 (s, 3F).
Anal. calcd. for C15H13Cl2F3N4S: C, 44.02%, H, 3.20%;
found: C, 43.85%, H, 3.06%.
Anal. calcd. for C12H7Cl2F3N4S: C, 39.25%, H, 1.92%;
found: C, 39.01%, H, 1.88%.
3.2.6. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-hexylthio-1H-pyrazole-3-carbonitrile (3g)
mp: 103–104 8C. IR (KBr): 3435, 3337, 3226, 2925, 2860,
2245, 1627, 1559, 1394, 1140, 882, 814 cmÀ1. NMR: 1H NMR
(300 MHz, C3D6O): d = 8.08 (s, 2H); 5.97 (s, 2H); 2.68 (t,
J = 7.02 Hz, 2H); 1.42–1.62 (m, 8H), 0.88 (t, J = 6.63 Hz, 3H).
13C NMR (75 MHz, C3D6O): d = 13.9 (1C), 22.7 (1C), 28.3
(1C), 28.6 (1C), 31.8 (1C), 36.1 (1C), 93.6 (1C), 113.5 (1C),
122.9 (q, J = 271.6 Hz, 1C), 126.8 (2C), 126.9 (2C), 132.6
(1C), 134.2 (q, J = 34.1 Hz, 1C), 136.9 (1C), 152.2 (1C).
19F NMR (220 MHz, C3D6O): d = À63.6 (s, 3F).
3.2.2. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-ethylthio-1H-pyrazole-3-carbonitrile (3c)
mp: 150–151 8C. IR (KBr): 3434, 3331, 3228, 2975, 2250,
1629, 1559, 1393, 1318, 1146, 880, 817 cmÀ1. NMR: 1H NMR
(300 MHz, C3D6O): d = 8.08 (s, 2H); 5.98 (s, 2H); 2.69 (q,
J = 7.3 Hz, 2H); 1.24 (t, J = 7.3 Hz, 3H). 13C NMR (75 MHz,
C3D6O): d = 14.2 (1C), 29.3 (1C), 92.7 (1C), 113.1 (1C), 122.5
(q, J = 271.5 Hz, 1C), 126.4 (4C), 132.3 (1C), 133.7 (q,
J = 34.1 Hz, 1C), 136.5 (1C), 151.5 (1C). 19F NMR (220 MHz,
C3D6O): d = À63.6 (s, 3F).
Anal. calcd. for C17H17Cl2F3N4S: C, 46.69%, H, 3.92%;
found: C, 46.41%, H, 3.82%.
Anal. calcd. for C13H9Cl2F3N4S: C, 40.96%, H, 2.38%;
found: C, 40.66%, H, 2.31%.
3.2.7. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-allylthio-1H-pyrazole-3-carbonitrile (3h)
3.2.3. 5-amino-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-
4-propylthio-1H-pyrazole-3-carbonitrile (3d)
mp: 141–142 8C. IR (KBr): 3430, 3330, 3225, 2922, 2243,
1
1625, 1553, 1392, 1142, 980, 910, 882, 814 cmÀ1. NMR: H
mp: 129–131 8C. IR (KBr): 3436, 3332, 3228, 2960, 2248,
1629, 1561, 1394, 1323, 1144, 887, 815 cmÀ1. NMR: 1H NMR
(300 MHz, C3D6O): d = 8.08 (s, 2H); 5.98 (s, 2H); 2.66 (t,
NMR (300 MHz, CDCl3): d = 7.79 (s, 2H); 5.85 (m, 1H); 5.02
(m, 1H), 4.88 (m, 1H), 4.15 (s, 2H), 3.26 (d, J = 7.53 Hz, 2H).
13C NMR (75 MHz, CDCl3): d = 39.5 (1C), 95.2 (1C), 110.1
(1C), 112.7 (1C), 118.7 (1C), 122.5 (q, J = 271.2 Hz, 1C),
126.2 (4C), 133.0 (1C), 134.4 (q, J = 34.2 Hz, 1C), 136.4
(1C), 150.0 (1C). 19F NMR (220 MHz, CDCl3): d = À63.6
(s, 3F).
J = 7.14 Hz, 2H); 1.60 (m, 2H); 1.02 (t, J = 7.30 Hz, 3H). 13
C
NMR (75 MHz, C3D6O): d = 12.4 (1C), 22.6 (1C), 38.6 (1C),
93.2 (1C), 113.1 (1C), 122.5 (q, J = 271.4 Hz, 1C), 126.38
(2C), 126.43 (2C), 132.1 (1C), 134.2 (q, J = 34.0 Hz, 1C),
136.5 (1C), 151.7 (1C). 19F NMR (220 MHz, C3D6O): d = 63.6
(s, 3F).
Anal. calcd. for C14H9Cl2F3N4S: C, 42.76%, H, 2.31%;
found: C, 42.66%, H, 2.13%.