Med Chem Res (2013) 22:1147–1162
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C25H24N2O5 (%): C, 69.43; H, 5.59; N, 6.48. Found: C,
69.16; H, 5.72; N, 6.33.
(E)-2-(4-bromophenyl)-7-(benzylidene)-3-(phenyl)-3,3a,
4,5,6,7-hexahydro-2H-indazoles (8a). Yield, 50 %; mp
1
168–169 ꢁC. H NMR (CDCl3); d: 1.32–3.15 (m, 7H, ali-
General method for the synthesis of (E)-7-(substituted
benzylidene)-3-(substituted phenyl)-3,3a,4,5,6,7-hexahy-
dro-2H-indazoles (7e–g) A mixture of the 2,6-diarylide-
necyclohexanones 5e–g (1 mmol), and hydrazine hydrate
(1 ml, 20 mmol) in absolute ethanol (15 ml) was heated at
reflux while stirring for 21 h. The reaction mixture was
then evaporated, and the residue obtained was washed with
water, collected by filtration, dried, and recrystallized from
ethanol to yield the title compounds.
phatic), 4.55 (d, 1H, NCH), 6.86–7.46 (m, 15H, 14Ar-H
and ylidene CH). Anal. Calcd for C26H23BrN2 (%): C,
70.43; H, 5.23; N, 6.32. Found: C, 69.92; H, 5.28; N, 6.25.
(E)-2-(4-bromophenyl)-7-(4-chlorobenzylidene)-3-(4-
chlorophenyl)-3,3a,4,5,6,7-hexahydro-2H-indazoles (8b).
Yield, 55 %; mp 98–100 ꢁC. 1H NMR (CDCl3); d:
1.08–3.08 (m, 7H, aliphatic), 4.51 (d, 1H, NCH),
6.64–7.58 (m, 13H, 12Ar-H and ylidene CH). Anal.
Calcd for C26H21BrCl2N2 (%): C, 60.96; H, 4.13; N,
5.47. Found: C, 59.41; H, 4.38; N, 5.80.
(E)-7-(2,5-dimethoxybenzylidene)-3-(2,5-dimethoxyphen-
yl)-3,3a,4,5,6,7-hexahydro-2H-indazoles (7e). Yield, 78 %;
mp 70–71 ꢁC. IR (KBr) mmax/cm-1 3338 (N–H), 1593
(C=N), 1497 (C=C), 1221(C–N). 1H NMR (CDCl3); d:
1.55–3.42 (m, 7H, aliphatic), 4.25 (s, 12H, 4OCH3), 5.00 (br
s, 1H, NH, D2O exchangeable), 5.32 (dd, 1H, NCH),
7.26–7.72 (m, 7H, 6Ar-H and ylidene CH). Anal. Calcd for
C24H28N2O4 (%): C, 70.57; H, 6.91; N, 6.86. Found: C,
70.32; H, 6.85; N, 7.02.
(E)-2-(4-bromophenyl)-7-(4-methoxybenzylidene)-3-(4-
methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-indazoles (8c).
Yield, 45 %; mp 70–72 ꢁC. IR (KBr) mmax/cm-1 1589
1
(C=N), 1499 (C=C), 1221 (C–N). H NMR (CDCl3); d:
1.12–3.13 (m, 7H, aliphatic), 3.73 (s, 3H, OCH3); 3.78 (s, 3
H, OCH3), 4.71 (d, 1H, NCH), 6.55–7.80 (m, 13H, 12Ar-H
and ylidene CH). MS m/z (%);503, M? (3.54), 135
(100.00). Anal. Calcd for C28H27BrN2O2 (%): C, 66.80; H,
5.41; N, 5.56. Found: C, 67.02; H, 5.33; N, 5.14.
(E)-7-(4-hydroxybenzylidene)-3-(4-hydroxyphenyl)-3,3a,
4,5,6,7-hexahydro-2H-indazoles (7f). Yield, 90 %; mp
166–168 ꢁC. IR (KBr) mmax/cm-1 3272 (N–H), 1606
(E)-2-(4-bromophenyl)-7-(3,4-dimethoxybenzylidene)-3-
(3,4-dimethoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-inda-
1
(C=N), 1510 (C=C), 1237 (C–N). H NMR (CDCl3); d:
zoles (8d). Yield, 45 %; mp 178–179 ꢁC. IR (KBr) mmax
/
1
1.41–3.41 (m, 7H, aliphatic), 5.32 (br s, 1H, NH, D2O
exchangeable), 5.52 (dd, 1H, NCH), 7.23–7.85 (m, 9H,
8Ar-H and ylidene CH), 9.8 (s, 2H, 2OH). MS m/z (%);
320, M? (3.67), 215 (100.00). Anal. Calcd for C20H20N2O2
(%): C, 74.98; H, 6.29; N, 8.74. Found: C, 74.65; H, 6.60;
N, 8.47.
cm-1 1595 (C=N), 1499 (C=C), 1227 (C–N).). H NMR
(CDCl3); d: 1.11–3.45 (m, 7H, aliphatic), 3.72; 3.77; 4.72
(s, 12 H, 4OCH3), 5.17 (d, 1H, NCH), 6.52–7.85 (m, 11H,
10Ar-H and ylidene CH). Anal. Calcd for C30H31BrN2O4
(%): C, 63.95; H, 5.55; N, 4.97. Found: C, 63.70; H, 5.27;
N, 4.40.
(E)-7-(4-hydroxy-3-methoxybenzylidene)-3-(4-hydroxy-3-
methoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-indazoles (7g).
Yield, 53 %; mp 179–180 ꢁC. IR (KBr) mmax/cm-1 3342
(E)-2-(4-bromophenyl)-7-(2,5-dimethoxybenzylidene)-3-
(2,5-dimethoxyphenyl)-3,3a,4,5,6,7-hexahydro-2H-inda-
zoles (8e). Yield, 60 %; mp 87–89 ꢁC. IR (KBr) mmax/cm-1
1588 (C=N), 1494 (C=C), 1219 (C–N).1H NMR (CDCl3);
d: 1.12–3.46 (m, 7H, aliphatic), 3.73; 3.78; 4.82 (s, 12H,
4OCH3), 5.07 (d, 1H, NCH), 6.42–7.80 (m, 11H, 10Ar-H
and ylidene CH). MS m/z (%); 563, M? (9.13), 212
(100.00). Anal. Calcd for C30H31BrN2O4 (%): C, 63.95; H,
5.55; N, 4.97. Found: C, 63.67; H, 5.46; N, 4.87.
1
(N–H), 1604 (C=N), 1514 (C=C), 1270 (C–N). H NMR
(CDCl3); d: 1.50–3.31 (m, 7H, aliphatic), 3.90 (s, 6H,
2OCH3), 5.10 (br s, 1H, NH, D2O exchangeable), 5.40 (dd,
1H, NCH), 7.22–7.82 (m, 7H, 6Ar-H and ylidene CH),
10.00 (s, 2H, 2OH). MS m/z (%); 380, M? (26.37), 378,
M?-2 (100.00). Anal. Calcd for C22H24N2O4 (%): C, 69.46;
H, 6.36; N, 7.36. Found: C, 69.21; H, 6.53; N, 7.71.
General method for the synthesis of (E)-2-(4-bromophe-
nyl)-8-((substituted) benzylidene)-3-((substituted) phenyl)-
2,3,3a,4,5,6,7,8-cyclohepta[c]pyrazoles (8h–j) A mixture
of the appropriate 2,7-bis(substituted benzylidene)cy-
cloheptanones 5h–j (1 mmol), 4-bromophenylhydrazine
hydrochloride (0.671 g, 3 mmol), and sodium ethoxide
(0.408 g, 6 mmol) in absolute ethanol (20 ml) was heated
under reflux for 20 h. The reaction mixture was then fil-
tered and the filtrate was concentrated. For compounds 8h
and 8i, purification on silica gel preparative TLC plates,
using n-hexane/ethyl acetate 1:1 as an eluent was done,
followed by crystallization from ethanol. For compound 8j,
General method for the synthesis of (E)-2-(4-bromophe-
nyl)-7-((substituted)benzylidene)-3-((substituted)phenyl)-3,
3a,4,5,6,7-hexahydro-2H-indazoles (8a–e) A mixture of
the appropriate 2,6-bis((substituted)benzylidene)cyclohexa-
nones 5a–e (1 mmol), 4-bromophenylhydrazine hydro-
chloride (0.671 g, 3 mmol), and sodium ethoxide (0.408 g,
6 mmol) in absolute ethanol (20 ml) was heated under
reflux for 20 h. The reaction mixture was then filtered and
the filtrate was concentrated. The separated solid was col-
lected by filtration, washed with water, and recrystallized
from ethanol.
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