4,5-Dioxo- and 4-oxo-2,3-diaryl-5-diazo-6,6-dimethyl-4,5,6,7- tetrahydroindazoles

Article abstract of DOI:10.1007/s10593-006-0028-z

The oxidation of 2,3-diphenyl-, 3-(4-chlorophenyl)-2-phenyl-, 3-(4-dimethylaminophenyl)-2-phenyl-, 3-(4-methoxyphenyl)-2-phenyl-, 2-phenyl-3-(3-pyridyl)-, 3-phenyl-2-(2-pyridyl)-, and 3-(4-dimethylaminophenyl)- 6,6-dimethyl-4-oxo-2-(2-pyridyl)-4,5,6,7-tet

Full text of DOI:10.1007/s10593-006-0028-z

Chemistry of Heterocyclic Compounds, Vol. 41, No. 12, 2005
4,5-DIOXO- AND 4-OXO-2,3-DIARYL-5-DIAZO-
6,6-DIMETHYL-4,5,6,7-TETRAHYDROINDAZOLES
I. Strakova, A. Strakovs, and M. Petrova
The oxidation of 2,3-diphenyl-, 3-(4-chlorophenyl)-2-phenyl-, 3-(4-dimethylaminophenyl)-2-phenyl-,
3-(4-methoxyphenyl)-2-phenyl-,
2-phenyl-3-(3-pyridyl)-,
3-phenyl-2-(2-pyridyl)-,
and
3-(4-dimethylaminophenyl)-6,6-dimethyl-4-oxo-2-(2-pyridyl)-4,5,6,7-tetrahydroindazoles using H2SeO3
in acetic acid in the presence of sulfuric acid gave the corresponding 4,5-dioxo derivatives. Reaction of
these with tosylhydrazine gave 4-oxo-5-tosylhydrazino derivatives which were decomposed by alkali to
give the corresponding 2,3-diaryl-5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles.
Keywords: α-diazo ketones, 2,3-diaryl-6,6-dimethyl-4,5-dioxo-4,5,6,7-tetrahydroindazoles.
6,6-Dimethyl-4,5-dioxo-4,5,6,7-tetrahydroindazoles have been prepared by oxidation of the
corresponding 6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles using H2SeO3 [1] and have found a variety of
uses in the modification of indazoles and pyrazoles [2-7]. On this basis pyrazole mono- and dicarboxylic acids
have been prepared by subsequent oxidation of the α-diketone with hydrogen peroxide [1, 4, 5], a benzyl
rearrangement [8], or cleavage of a tosylate monoxime [9]. The α-diketone group has been used in the synthesis
of polycondensed pyrazolo[4,3-a]phenazine [2, 6, 7] and indazolo[4,5-d]imidazole [6] heterocyclic systems.
Me
Me
Me
Me
N
N
N
N
O
Ar
Ar
O
O
Ar1
Ar1
1a–g
2a–g
Me
Me
Me
Me
N
N
N
N
+
N
N
Ar
–
N
Ar
N
O
Ar1
O
Ar1
MeC6H4O2S
H
4a–g
3a–g
1-4 a Ar = Ar1 = Ph; b Ar = Ph, Ar1 = C6H4Cl-4; c Ar = Ph, Ar1 = C6H4NMe2-4;
d Ar = Ph, Ar1 = C6H4OMe-4; e Ar = Ph, Ar1 = C5H4N-3; f Ar = C5H4N-2, Ar1 = Ph;
g Ar = C5H4N-2, Ar1 = C6H4NMe2-4
__________________________________________________________________________________________
Riga Technical University, Riga LV-1048, Latvia; e-mail: marina@osi.lv. Translated from Khimiya
Geterotsiklicheskikh Soedinenii, No. 12, pp. 1829-1833, December, 2005, Original article submitted April 8,
2002; revision submitted September 29, 2003.
0009-3122/05/4112-1507©2005 Springer Science+Business Media, Inc.
1507

TABLE 1. Characteristics of Compounds 2-4
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
mp, °С
Yield, %
С
H
N
S
2a
2b
2c
2d
2e
2f
C21H18N2O2
C21H17ClN2O2
C23H23N3O2
C22H20N2O3
C20H17N3O2
C20H17N3O2
C22H22N4O2
C28H26N4O3S
C28H25 ClN4O3S
C30H31N5O3S
C29H28N4O4S
C27H25N5O3S
C27H25N5O3S
C29H30N6O3S
C21H18N4O
76.11
76.34
69.00
69.13
73.80
73.97
73.10
73.32
72.33
72.49
72.38
72.49
70.45
70.57
67.37
67.45
63.17
63.09
66.36
66.52
65.70
65.89
64.72
64.91
64.65
64.91
64.02
64.19
73.55
73.66
66.76
66.93
5.55
5.49
4.55
4.70
6.22
6.21
5.49
5.59
5.14
5.17
5.09
5.17
5.90
5.92
5.21
5.26
4.61
4.71
5.70
5.77
5.31
5.34
4.92
5.04
5.00
5.04
5.43
5.57
5.21
5.30
4.40
4.55
8.41
8.48
7.62
7.68
11.14
11.25
7.60
7.77
12.62
12.68
12.79
12.68
14.88
14.96
11.11
11.24
10.40
10.51
12.78
12.93
10.45
10.60
14.14
14.02
14.11
14.02
15.40
15.49
16.21
16.36
14.69
14.87
162-163
180-181
222-224
171-172
156-157
175-176
212-214
68
48
67
71
74
72
79
41
49
39
51
36
33
27
70
66
60
39
68
65
70
—*
2g
3a
3b
3c
3d
3e
3f
6.30
6.43
153-154
(dec.)
177-179
(dec.)
187-188
(dec.)
164-166
(dec.)
153-154
(dec.)
163-164
(dec.)
181-182
(dec.)
161-163
(dec.)
168-169
(dec.)
170-171
(dec.)
140-142
(dec.)
170-171
(dec.)
142-143
(dec.)
161-163
(dec.)
5.70
5.92
5.90
6.07
6.20
6.42
6.20
6.42
3g
4a
4b
4c
4d
4e
4f
5.70
5.91
C21H17ClN4O
C23H23N5O
—*2
71.50
71.66
70.88
70.95
69.80
69.95
69.90
69.95
5.89
5.01
5.29
5.41
5.02
4.99
4.82
4.99
18.00
18.17
14.90
15.05
20.20
20.40
20.22
20.40
C22H20N4O2
C20H17N5O
C20H17N5O
4g
C22H22N6O
68.28
68.37
5.62
5.74
21.80
21.75
_______
* Found, %: Cl 9.60; calculated, %: Cl 9.72.
*2 Found, %: Cl 9.20; calculated, %: Cl 9.41.
α-Oxocyclohexene heterocycles other than 4-oxo-4,5,6,7-tetrahydroindazoles were oxidized by
selenious acid. The oxidation of 3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydroindoxazene [10] gives the
corresponding 4,5-dioxo derivative while oxidation of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinazolines
[11] gives the 6,8-epidiseleno derivative.
Oxidation of the 2,3-diaryl-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles 1a-g [12, 13] was carried out
using the method reported in [5-7]. The α-dicarbonyl structural fragment in the 4,5-dioxo derivatives 2a-g
produced gave two characteristic IR spectroscopic frequencies at 1735-1725 (ν C(5)=O) and 1690-1670 cm-1
(ν C(4)=O). Refluxing these dioxo derivatives 2a-g with an equimolar amount of tosylhydrazine for 5 h gave the
corresponding 4-oxo-5-tosylhydrazono-4,5,6,7-tetrahydroindazoles 3a-g which contain an intramolecular
1508

hydrogen bond (ν CO 1650-1640 cm-1, δ NH 12.8 ppm). The decomposition of the α-diketone monohydrazones
3 using an aqueous ethanol solution of alkali [14] gave the diazo ketones 4a-g which are characterized in the IR
spectrum by the diazo group absorption at 2100-2080 cm-1 and the C=O absorption at 1630-1620 cm-1. The
1H NMR spectra of the diketone 2, tosylhydrazones 3, and diazo ketones 4 showed proton signals for all of the
structural fragments in these compounds.
TABLE 2. IR and 1H NMR Spectra of the Compounds Synthesized
IR spectrum,
Com-
pound
1Н NMR spectrum, δ, ppm (J, Hz)
ν, cm-1
2a
2b
2c
1730, 1685 1.35 (6H, s, 2CH3); 3.12 (2H, s, CH2); 7.29 (10H, m, 2C6H5)
1727, 1688 1.36 (6H, s, 2CH3); 3.11 (2H, s, CH2); 7.33 (9H, m, C6H4, C6H5)
1733, 1690 1.37 (6H, s, 2CH3); 2.92 (6H, s, N(CH3)2); 3.12 (2H, s, CH2);
6.57 (2H, m, 3J = 8, C6H4); 7.27 (7H, m, C6H4, C6H5)
2d
2e
1732,
1.36 (6H, s, 2CH3); 3.09 (2H, s, CH2); 3.73 (3H, s, OCH3);
1690-1680 6.81 (2H, m, 3J = 8.5, C6H4); 7.22 (7H, m, C6H4, C6H5)
1735, 1685 1.41 (6H, s, 2CH3); 3.25 (2H, s, CH2); 7.26 (5H, m, C6H5);
7.89 (2H, dt, 3J = 8, 4J = 1.5, C5H4N); 8.47 (1H, d, 4J=1.5, C5H4N);
8.61 (1H, dd, 3J = 5, 4J = 1.5, C5H4N)
2f
1730, 1680 1.42 (6H, s, 2CH3); 3.24 (2H, s, CH2); 7.16-7.82 (8H, m, C5H4N, С6Н5);
8.56 (1H, dd, 3J = 5, J = 1.5, C5H4N)
2g
1728, 1685 1.33 (6H, s, 2CH3); 2.91 (6H, s, N(CH3)2); 3.14 (2H, s, CH2);
6.51 (2H, m, 3J = 8, C6H4); 7.01-7.71 (5H, m, C6H4, C5H4N);
8.53 (1H, dd, 3J = 5, 4J = 1.5, C5H4N)
3a
3b
3c
1645, 3190 1.22 (6H, s, 2CH3); 2.37 (3H, s, CH3); 2.86 (2H, s, CH2); 7.25 (12H, m,
2C6H5, C6H4); 7.81 (2H, m, 3J = 8, C6H4); 12.83 (1H, br. s, NН)
1642; 3200 1.22 (6H, s, 2CH3); 2.33 (3H, s, CH3); 2.29 (2H, s, CH2); 7.28 (11H, m,
C6H5, 2C6H4); 7.75 (2H, m, 3J = 8, C6H4); 12.81 (1H, br. s, NН)
1640, 3170 1.22 (6H, s, 2CH3); 2.36 (3H, s, CH3); 2.86 (2H, s, CH2);
2.94 (6H, s, N(CH3)2); 6.53 (2H, m, 3J = 8, C6H4); 7.28 (9H, m,
C6H5, C6H4); 7.83 (2H, m, 3J = 8, C6H4); 12.81 (1H, br. s, NН)
3d
3e
3f
1644,
1.25 (6H, s, 2CH3); 2.31 (3H, s, CH3); 2.94 (2H, s, CH2);
3200-3170 3.78 (3H, s, OCH3); 6.78 (2H, m, 3J = 8, C6H4); 7.17 (9H, m,
C6H5, C6H4); 7.72 (2H, m, 3J = 8, C6H4); 12.81 (1H, br. s, NН)
1641, 3200 1.21 (6H, s, 2CH3); 2.39 (3H, s, CH3); 2.89 (2H, s, CH2);
7.19-7.81 (11H, m, C6H5, C6H4, C5H4N); 8.42 (1H, d, 4J = 1.5, C5H4N);
8.47 (1H, dd, 3J = 5, 4J = 1.5, C5H4N); 12.81 (1H, br. s, NН)
1640, 3180 1.19 (6H, s, 2CH3); 2.36 (3H, s, CH3); 2.92 (2H, s, CH2);
7.28-7.83 (12H, m, C6H5, C6H4, C5H4N); 8.33 (1H, dd, 3J = 5, 4J = 1.5,
C5H4N); 12.84 (1H, br. s, NН)
3g
1644, 3190 1.20 (6H, s, 2CH3); 2.39 (3H, s, CH3); 2.92 (2H, s, CH2); 2.98 (6H, s,
N(CH3)2); 6.58 (2H, m, 3J = 8, C6H4); 7.30-7.44 (7H, m, C6H4, C5H4N);
7.81 (2H, m, 3J = 8, C6H4); 8.50 (1H, dd, 3J = 5, 4J = 1.5, C5H4N);
12.92 (1H, br. s, NН)
4a
4b
4c
1620, 2090 1.33 (6H, s, 2CH3); 2.84 (2H, s, CH2); 7.26 (10H, m, 2C6H5)
1623, 2095 1.34 (6H, s, 2CH3); 2.92 (2H, s, CH2); 7.28 (9H, m, C6H5, C6H4)
1622, 2095 1.33 (6H, s, 2CH3); 2.82 (2H, s, CH2); 2.86 (6H, s, N(CH3)2);
6.56 (2H, m, 3J = 8, C6H4); 7.22 (7H, m, C6H5, C6H4)
4d
4e
4f
1620, 2090 1.33 (6H, s, 2CH3); 2.84 (2H, s, CH2); 3.73 (3H, s, ОCH3); 6.81 (2H, m,
3J = 8, C6H4); 7.22 (5H, m, C6H5); 7.24 (2H, m, 3J = 8, C6H4)
1620, 2100 1.40 (6H, s, 2CH3); 2.93 (2H, s, CH2); 7.22 (6H, m, C6H5, C5H4N);
7.87 (1H, m, C5H4N); 8.47 (2H, m, C5H4N)
1622, 2100 1.36 (6H, s, 2CH3); 2.93 (2H, s, CH2); 6.95-7.71 (8H, m, C6H5, C5H4N);
8.40 (1H, dd, 3J = 5, 4J = 1.5, C5H4N)
4g
1619, 2095 1.36 (6H, s, 2CH3); 2.93 (2H, s, CH2); 2.95 (6H, s, N(CH3)2); 6.53 (2H, m,
3
3J = 8, C6H4); 6.97-7.68 (5Н, m, C5H4N, С6Н4); 8.51 (1H, dd, J = 5,
4J = 1.5, C5H4N)
1509

EXPERIMENTAL
IR spectra were recorded on a Specord IR-75 instrument for a suspension of the material in vaseline oil
(1800-1500 cm-1 region) and in hexachlorobutadiene (3600-2000 cm-1 region). Only the carbonyl absorption
bands are reported for the region 1800-1500 cm-1. The absorption bands for the C–H stretching vibrations in the
1
region 3050-2800 cm-1 are not reported. H NMR spectra were recorded on a Bruker WH/90 DS instrument
(90 MHz) using CDCl3 solvent and HMDS as internal standard (δ 0.05 ppm).
2,3-Diaryl-6,6-dimethyl-4,5-dioxo-4,5,6,7-tetrahydroindazoles 2a-g. Finely pulverized H2SeO3
(4 mmol) in conc. H2SO4 (4 mmol, in the case of 1c-g 8 mmol) was added to a solution of the 4-oxo-4,5,6,7-
tetrahydroindazole 1a-g (4 mmol) in glacial acetic acid (15 ml). The reaction mixture was left for 4 days with
occasional shaking and then heated for 2 h on a boiling water bath. The hot mixture was filtered from the black
selenium precipitate. The filtrate was poured into crushed ice and a dilute (1:1) solution of ammonium hydroxide
was added until turbidity ceased and a precipitate was formed. The precipitate of the diketone 2 was filtered off.
Compounds 2a,e-g were recrystallized from a mixture of ethyl acetate and hexane (1:1), 2b,d from ethyl acetate,
and 2c from a mixture of ethyl acetate and benzene.
2,3-Diaryl-6,6-dimethyl-4-oxo-5-tosylhydrazono-4,5,6,7-tetrahydroindazoles
3a-g.
Separately
prepared, hot solutions of diketone 2 (2 mmol) in ethanol (20 ml) and of tosylhydrazine (2 mmol) in ethanol
(10 ml) were mixed and heated for 6 h. Hot water (5 ml) was added to the hot mixture and the product was
allowed to stand for 1 day in the fridge. The precipitated tosylhydrazone 3 was filtered off and recrystallized
from 80% ethanol (compounds 3a,b), ethanol (3c-f), or a mixture of ethyl acetate and hexane (3g).
2,3-Diaryl-5-diazo-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazoles 4a-g. A suspension of the
tosylhydrazone 3 (0.5 mmol) in aqueous sodium hydroxide (2%, 15 ml) was heated for 1 h on a boiling water
bath, gradually adding ethanol (3 ml). The reaction mixture was cooled and the precipitated yellow diazo ketone
4 was filtered off, carefully washed with water on the filter to the disappearance of an alkaline reaction, and
recrystallized from a mixture of ethyl acetate and hexane (4a,c-g) or a mixture of benzene and hexane (4b).
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1510