Synthesis and structure of new oxoindoles

Article abstract of DOI:10.1007/s10593-007-0045-6

The synthesis and study of the structure of new oxoindoles has been carried out. The molecular and crystal structure, and the stereochemistry atom of C(3) of 1,2-diacetyl-5′-phenyl(2′,4′ dihydrospiro[3H-indol-3, 3′-[3H]pyrazol]-2-(1H)-one have been establ

Full text of DOI:10.1007/s10593-007-0045-6

Chemistry of Heterocyclic Compounds, Vol. 43, No. 3, 2007
SYNTHESIS AND STRUCTURE OF NEW OXOINDOLES
F. Z Macaev1, O. M. Radul1, I. N. Shterbet1, S. I. Pogrebnoi1, N. S. Sucman1,
S. T. Malinovskii1*, A. N. Barba1, and M. Gdaniec2
The synthesis and study of the structure of new oxoindoles has been carried out. The molecular and
crystal structure, and the stereochemistry atom of C(3) of 1,2-diacetyl-5'-phenyl(2',4'dihydrospiro[3H-
indol-3,3'-[3H]pyrazol]-2-(1H)-one have been established by X-ray crystallography.
Keywords: oxoindole, 3-(2-aryl-2-oxoethylidene)-2-indolinones, spirooxoindoles, X-ray crystallography.
Derivatives of indole, which are widely distributed in nature, are of primary importance for living
creatures, and such compounds, not extracted from natural sources, are used as medicinals. As in the past this is
a stimulus for the development of new methods of synthesis for both known and new derivatives of indole [1-5].
3-(2-Aryl-2-oxoethylidene)-2-indolinones and products of their heterocyclization, which have a variety of
physiological activities are of especial interest [6-14].
O
O
N
R
1–7
R 1
R1
R1
R1
R1
R1
H
N
O
O
OH
NR2
O
O
O
N
N
N
R
R
R
28–33
8–17
18–27
1,8,11,18,19,28,29 R = H, 2,9,12,20,21,30 R = Me, 3,10,13,22,23,31,33 R = Et, 4,14,24 R = n-Bu,
5,15,25 R = n-C6H13, 6,16,26 R = n-C9H19, 7,17,27 R = n-C10H21, 32 R = Ac;
8−10,18,20,22,28,32 R1 = H, 11−17, 19,21, 23−27, 29−31, 33 R1 = Cl; 28−31 R2 = H, 32,33 R2 = Ac
_______
* Deceased.
__________________________________________________________________________________________
1Institute of Chemistry, Moldova Academy of Sciences, Chisinau MD2028, Moldova; e-mail:
2
flmacaev@cc.acad.md. Faculty of Chemistry, A. Mickiewicz University, 60-870 Poznan, Poland; e_mail:
magdan@main.amu.edu.pl. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, 374-382, March
2007. Original article submitted March 1, 2004. Revised version submitted October 24, 2006.
298
0009-3122/07/4303-0298©2007 Springer Science+Business Media, Inc.

With the objectives of broadening the range of compounds in the oxoindole series with potential
biological activity and in continuing our study of synthetic reactions of indoline-2,3-dione (1) [15-18] we have
investigated suitable routes for its conversion into 1-alkylindoline-2,3-diones 2-7 and compounds 8-13.
Table 1. Properties and Characteristics of the Synthesized Compounds 8-33
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
Yield,
%
mp, °C*
С
H
CI
—
—
—
N
8
C16H13NO3
71.90
71.68
72.58
72.49
73.20
73.24
57.17
57.20
58.31
58.18
59.36
59.30
61.24
60.77
62.86
62.41
64.94
64.82
65.54
64.97
77.10
76.99
60.40
60.33
77.55
77.53
61.47
60.99
77.96
77.93
62.45
62.51
64.18
64.02
65.68
65.81
67.57
67.89
68.12
68.00
72.99
72.78
57.85
58.01
58.98
58.75
60.01
60.00
4.90
4.73
5.37
5.06
5.80
5.70
5.24
5.21
4.98
4.90
4.74
4.60
4.17
4.07
4.00
4.12
3.85
4.00
3.57
3.71
3.33
3.30
3.03
2.96
2.94
3.13
5.62
5.38
4.40
4.32
5.32
5.19
4.22
4.45
5.05
4.91
4.05
4.39
3.74
3.90
3.48
3.37
3.15
3.30
3.06
2.87
15.96
16.07
12.65
12.37
12.14
12.25
11.66
11.78
178-180
172-175
120-121
164-165
161-164
135-138
Oil
79
75
68
41
90
62
95
91
94
97
88
59
85
94
79
98
94
97
93
96
66
38
34
35
80
69
9
C17H15NO3
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
C18H17NO3
C16H11Cl2NO3
C17H13Cl2NO3
C18H15Cl2NO3
C20H19Cl2NO3
C22H23Cl2NO3
C25H29Cl2NO3
C26H31Cl2NO3
C16H11NO2
3.30
3.09
21.09
21.28
3.74
3.72
20.25
20.09
4.15
3.91
19.47
19.39
4.88
4.74
18.08
18.13
5.52
5.82
16.87
16.88
Oil
6.32
6.21
15.33
15.28
Oil
6.56
6.61
14.88
14.83
Oil
4.45
4.77
—
195-197
226-227
131-132
175-176
131-132
98-100
Oil
C16H9Cl2NO2
C17H13NO2
2.85
2.90
22.29
22.17
4.98
4.87
—
C17H11Cl2NO2
C18H15NO2
3.34
3.59
21.35
21.17
5.45
5.44
—
C18H13Cl2NO2
C20H17Cl2NO2
C22H21Cl2NO2
C25H27Cl2NO2
C26H29Cl2NO2
C16H13N3O
3.78
3.78
20.48
20.52
4.58
4.41
18.95
18.99
5.26
5.10
17.62
17.59
Oil
6.12
6.14
15.96
15.83
Oil
6.38
6.47
15.47
15.39
Oil
4.98
4.76
—
202-208
224-225
200-201
161-164
173-174
204-207
C16H11Cl2N3O
C17H13Cl2N3O
C18H15Cl2N3O
C20H17N3O3
3.34
3.66
21.35
21.22
3.78
3.77
20.48
20.59
4.20
4.34
19.68
19.71
69.15
69.01
59.71
59.73
4.93
4.90
—
12.10
11.97
10.45
10.26
C20H17Cl2N3O2
4.26
4.39
17.63
17.54
_______
* Solvent for recrystallization: EtOH (compounds 8,10,13,21-23, 30),
i-PrOH (compounds 9, 11, 12, 18, 19, 28, 29, 32, 33), benzene (compounds
20, 31).
299

We have previously reported [9] that 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one (8) was obtained
from the condensation of isatin with acetophenone in dry EtOH. We have established that this conversion can
also be carried out in a mixture of H2O-i-PrOH-Et2NH, which simplified the process without decreasing the
yield. Use of these reaction conditions permitted the synthesis of products 9 and 10 (Table 1).
It is known that the presence of halogen atoms in a molecule leads to an increase in or the appearance of
biological activity [9, 19, 20]. The oxoindoles 11-17 containing the 2,4-dichlorophenyl unit were synthesized
from N-alkylisatins 4-7 and 2,4-dichloroacetophenone. Note somewhat increased yields of the aldols 11-13 in
comparison with their analogs 8-10 (Table 2).
The standard procedure for dehydration of the alcohols 8-17 with a mixture of hydrochloric and
ethanolic acids led to a new α,β-unsaturated ketones 18-27, among analogs of which are substances known to be
active against Plasmodium falciparum [13].
1
Interaction of enone 18 with hydrazine hydrate gave the spiran 28 in the H NMR spectrum of which
there are signals for methylene and aromatic protons, and also two NH protons of the pyrazolin (7.92 ppm) and
indolinone (10.4) rings respectively. It should be noted that the opposite assignment of these protons was given
1
in [9]. Comparative analysis of the H NMR spectra of compounds 28-31 confirms our interpretation because
substitution of the amide proton by an alkyl substituent led to the extinction in the spectra of compounds 28 and
29 of the signals at 10.40 and 10.53 ppm and the retention of the signals at 8.16 and 7.98 ppm respectively.
Table 2. IR Spectra of Compounds 8-33
Compound
ν, cm-1
8
1670, 1690 (C=O), 3240 (NH), 3270-3350 (OH)
1650, 1685 (C=O), 3330-3400 (OH)
1655, 1690 (C=O), 3320-3390 (OH)
780 (С–Сl), 1645, 1680 (C=O), 3100 (NH), 3290-3350 (OH)
775 (С–Сl), 1645, 1680 (C=O), 3330-3390 (OH)
775 (С–Сl), 1655, 1690 (C=O), 3200-3400 (OH)
775 (С–Сl), 1645, 1680 (C=O), 3230-3400 (OH)
780 (С–Сl), 1655, 1675 (C=O), 3300-3400 (OH)
770 (С–Сl), 1650, 1685 (C=O), 3240-3400 (OH)
780 (С–Сl), 1660, 1685 (C=O), 3380 (OH)
1670, 1675 (C=O), 3440 (NH)
9
10
11
12
13
14
15
16
17
18
19
20
23
24
25
26
27
28
29
30
31
32
33
770 (С–Сl), 1670, 1675 (C=O), 3150 (NH)
1665, 1675 (C=O), 3280 (NH)
780 (С–Сl), 1670, 1685 (C=O),
770 (С–Сl), 1655, 1675 (C=O)
785 (С–Сl), 1665, 1670 (C=O)
770 (С–Сl), 1655, 1685 (C=O)
780 (С–Сl), 1660, 1685 (C=O)
1630 (C=N), 3300–3150 (NH)
1635 (C=N), 3350–3150 (NH)
1630 (C=N), 3300–3150 (NH)
780 (С–Сl), 1620 (C=N), 1685 (C=O), 3280 (NH)
1635 (C=N), 1655, 1680 (C=O)
780 (С–Сl), 1625 (C=N), 1675 (C=O)
_______
* 13C NMR Spectrum, δ, ppm: 175.26, 172.13, 170.42, 167.36, 153.35,
139.0, 130.20, 129.13, 67,45, 26.15, 21.33.
300

There has been no study of the stereochemistry of the atom C(3) of the spiro compound 28 by X-ray
crystallography [21]. We attempted to prepare monocrystals of compound 28 suitable for X-ray crystallography
but were unsuccessful. In this connection compound 28 was converted into the acetyl derivative 32. An
investigation of a monocrystal of composition C20H17N3O3 by X-ray crystallography showed that its molecular
Fig. 1 Molecular structure of compound 32
Fig. 2. Crystal structure of compound 32 along the direction [010]
301

structure consisted of four rings: two phenyl, pyrrolidinyl, and pyrazolinyl (Fig. 1). The aromatic rings lie
practically in one plane with adjoining pyrazolin and pyrrollidinone units at dihedral angles of 1.9(1) and 1.6(1)°
respectively.
Table 3. 1H NMR Spectra of Compounds 8-33
Com-
pound
1Н NMR spectrum,
δ
, ppm. (
= 10.8, = 15.2, СН2),
= 8, = 14.8, СН2), 4.31 (1Н, s, ОН),
J, Hz)
8
3.58 (1Н, s, ОН), 3.84, 3.95 (2Н, d, d,
J
J
6.15-7.94 (9Н, m, arom.), 10.31 (1Н, NH)
9
3.18 (3Н, s, CH3), 3.51, 3.62 (2Н, d, d,
6.10-7.74 (9Н, m, arom.)
J
J
10
11
12
13
14
15
16
17
1.30 (3Н, t,
6.61-7.92 (9Н, m, arom.)
3.58, 3.68 (2Н, d, d, = 11.2,
6.76-7.62 (7Н, m, arom.), 10.32 (1Н, NH)
3.18 (3Н, s, CH3), 3.51, 3.62 (2Н, d, d, = 11.5,
4.31 (1Н, s, ОН), 6.10-7.74 (9Н, m, arom.)
1.27 (3Н, t, = 7.2, CH3), 3.44-3.94 (4Н, m, 2СН2), 4.65 (1Н, s, ОН),
J = 7.2, CH3), 3.46-4.01 (4Н, m, 2СН2), 4.78 (1Н, s, ОН),
J
J = 14.5, СН2), 6.19 (1Н, s, ОН),
J
J = 18.3, СН2),
J
6.78-7.52 (7Н, m, arom.)
0.97-1.34 (7Н, m, CH3(СН2)2), 3.26-4.01 (4Н, m, CH3СН2, NCH2),
4.63 (1Н, s, ОН), 6.71-7.73 (7Н, m, arom.)
0.87-1.47 (11Н, m, CH3(СН2)4), 3.20-3.89 (4Н, m, CH3СН2, NCH2),
4.57 (1Н, s, ОН), 6.61-7.79 (7Н, m, arom.)
0.80-1.25 (15Н, m, CH3(СН2)7), 3.23-3.92 (4Н, m, CH3СН2, NCH2),
4.70 (1Н, s, ОН), 6.80-7.71 (7Н, m, arom.)
0.92-1.46 (17Н, m, CH3(СН2)8), 3.01-3.93 (4Н, m, CH3СН2, NCH2),
4.57 (1Н, s, ОН), 6.78-7.67 (7Н, m, arom.)
18
19
20
23
6.83-8.14 (9Н, m, arom.), 7.71 (1H, s, C=CH), 10.83 (1Н, NH)
6.84-8.35 (7Н, m, arom.), 7.75 (1H, s, C=CH), 10.86 (1Н, NH)
3.15 (3Н, s, CH3), 6.64-8.27 (9Н, m, arom.), 7.78 (1H, c, C=CH)
1.20 (3Н, t,
J = 7.2, CH3), 3.70 (2Н, q, J = 7.2, СН2), 6.69-8.52 (7Н, m, arom.),
7.51 (1H, s, C=CH)
24
25
26
27
28
29
0.90-1.31 (7Н, m, CH3(СН2)2), 3.06-3.96 (4Н, m, CH3СН2, NCH2),
6.71-7.73 (7Н, m, arom.), 7.76 (1H, c, C=CH)
0.71-1.32 (11Н, m, CH3(СН2)4), 3.40-3.59 (4Н, m, CH3СН2, NCH2),
6.60-7.84 (8Н, m, arom., С=СН)
0.67-1.33 (15Н, m, CH3(СН2)7), 3.87-3.90 (4Н, m, CH3СН2, NCH2),
6.80-7.77 (8Н, m, arom., С=СН)
0.82-1.26 (17Н, m, CH3(СН2)8), 2.85-3.91 (4Н, m, CH3СН2, NCH2),
6.78-7.67 (8Н, m, arom., С=СН)
3.15-3.95 (2Н, m, СН2), 6.82-7.84 (9Н, m, arom.), 7.92 (1Н, s, NNH),
10.40 (1Н, CONH)
3.18-3.65 (2Н, m, СН2), 6.85-7.76 (7Н, m, arom.), 8.21 (1Н, s, NNH),
10.53 (1Н, CONH)
30
31
3.14 (3Н, s, CH3), 3.37-3.61 (2Н, m, СН2), 6.97-7.78 (7Н, m, arom.), 8.16 (1Н, s, NNH)
1.25 (3Н, t, J=7.2, CH3), 3.40-4.01 (4Н, m, 2СН2), 6.95-7.84 (7Н, m, arom.),
7.98 (1Н, s, NNH)
32*
33
2.26, 2.59 (6Н, s, s, 2CH3), 3.68, 3.75 (2H, d, d,
7.12-8.21 (7Н, m, arom.)
J = 8, J = 13.3, СН2),
1.25 (3Н, t,
J = 7.2, CH3), 2.26 (3Н, s, СОCH3), 3.46-4.01 (4H, m, 2СН2),
6.95-7.84 (7Н, m, arom.)
_______
* 13C NMR Spectrum, δ, ppm: 175.26, 172.13, 170.42, 167.36, 153.35,
139.0, 130.20, 129.13, 67,45, 26.15, 21.33.
302

The dihedral angle formed by the pyrrolidinone and pyrazoline cycles, which form the spiro bond at
C(3), is 89.2(1)°. The five membered rings with the benzoyl groups have different compositions, namely: the
vicinal coupling at atom C(8)-C(9) with carbon-carbon bond C(16)-C(21) leads to differences in coplanarity of
these rings. The displacements of atoms from the least mean squares plane of the pyrazoline ring are: C(3) 0.005,
C(2) -0.005, N(1) 0.003, C(8) 0, C(9) -0.003 Å. The displacements of atoms from the pyrrolidinone ring are:
C(3) 0.031, N(14) -0.023, C(16) 0.021, C(17) -0.031Å. Evidently in both cases there is a tendency to a distorted
envelope conformation. The carbonyl atom O(10) is coplanar with the plane of pyrrolidinone ring with a
precision of 0.017 Å, while atoms O(12) and C(13) deviate from the latter by -0.206 and 0.256 Å, while the
torsion angle O(10)-C(2)-C(3)-C(9) is 0.8°. The acetyl groups do not lie in the planes of the rings, the torsion
angles C(8)-N(1)-C(11)-O(12) and C(3)-N(14)-C(18)-O(19) equal -10.9 and 4.6° respectively. The
displacements of atoms O(19) and C(20) from the pyrrolidinone unit are -0.377 and -0.421 Å respectively.
Thus, taking into account the conformation of the molecule as a whole and the fact that the displacement of
atoms N(14) and C(17) of the pyrazoline ring from the least squares plane of the pyrollidinone ring are -1.662(2)
and 1.164(3) Å respectively, it may be concluded that C(3) has the S-conformation in the investigated structure
of 32. The interatomic distances and bond angles in the pyrazoline and pyrrolidinone rings are not equivalent, In
the former N(15)-C(16) has bond order 2, whereas in the second N(1)-C(2) has bond order 1.5, with lengths of
1.286(2) and 1.407(2) Å respectively, which leads to partial delocalization of the electrons in these rings and the
neighboring units with formation C=O carbonyl double bonds. Thus the carbonyl atom O(10) of the
pyrrolidinone ring and the carbonyl atoms of the acetyl groups O(12) and O(13) have exclusively accept or
properties, as a result of which the structure is stabilized by the formation of intramolecular hydrogen bonds
C(7)-H(7)…O(12) with the parameters C(7)-H(7) 0.991, C(7)…O(12) 2.848, H(7)…O(12) 2.239 Å, and the
angles at the hydrogen atom of 111.7°. This hydrogen bond permits the discussion of an additional six-
membered C(7).C(8).N(1)C(11).O(12).H(7) "pseudoring". It is also established that the basic role in the
formation of the crystal structure is played by the intermolecular bonds C(7)-H(7)…O(19) [1-x, 0.5+y, 0.5-z]
with parameters C(7)-O(19) 3.182(2), H(7)…O(19) 2.50(2) Å and the angle at the hydrogen atom of 126(1)°,
which joins crystallographically independent molecules with a symmetrical bond with the production of a
centrosymmetric dimer. A portion of the crystal structure along the [010] direction is shown in Fig. 2.
Compound 33 was synthesized in conditions analogous to those used for compound 32.
Thus syntheses of new N-alkylisatins and their aldol condensations with acetophenone and
2,4-dichloroacetophenone have been accomplished, It is shown that the synthesized 3-(2-oxo-2-arylethylidene)-
2-indolinones cyclize on reaction with hydrazine hydrate into spiro compounds with S-configuration at the C(3)
connection.
EXPERIMENTAL
1H and 13C NMR Spectra were recorded on a Bruker AC-80 (80 and 20 MHz) spectrometer in 2-3%
(CD3)2SO solution for compounds 8, 11, 18-20, 28-30, CDCl3 for compounds 9, 10, 12-17, 21-27 and CD3CN for
compounds 31, 33 with TMS as internal standard. IR spectra of nujol mulls were recorded on a Specord 74-1
instrument. Experimental collection of X-ray crystallographic data was carried out on a KM4CCD diffractometer
using ω-scanning. Melting points were determine with a Boetius block. The course of reactions and purity of
compounds were monitored by TLC on Sorbfil UV-254 strips.
1-Alkylindoline-2,3-diones 2-7. Compounds 2 and 3 were obtained by a known method [18].
Compounds 4-7 were synthesized analogously.
1-Butylindoline-2,3-dione (4). A reddish oil, Rf 0.65 (CHCl3). IR spectrum, ν, cm-1: 1735 (C=O).
Found, %: C 70.81, H 6.40, N 6.78. Calculated for C12H13NO2, %: C 70.92, H 6.45, N 6.89.
1-Hexylindoline-2,3-dione (5). Reddish oil, Rf 0.60 (CHCl3). IR spectrum, ν, cm-1: 1750 (C=O). Found,
%: C 72.51, H 7.44, N 5.97. Calculated for C14H17NO2, %: C 72.70, H 7.41, N 6.06.
303

1-Nonylindoline-2,3-dione (6). Reddish oil, Rf 0.63 (CHCl3) IR spectrum, ν cm-1: 1745 (C=O). Found,
%: C 74.57, H 8.47, N 5.02. Calculated for C17H23NO2, %: 74.69, H 8.48, N 5.12.
1-Decylindoline-2,3-dione (7). Reddish oil, Rf 0.66 (CHCl3). IR spectrum, ν, cm-1: 1735 (C=O). Found,
%: C 75.20, H 8.67, N 5.02. Calculated for C18H25NO2, %: C75.22, 8.77, 4.87.
Synthesis of Alcohols 8-17 (General Method). Acetophenone (0.04 mol) (or 2,4-dichloro-
acetophenone) and diethylamine (2.92 g, 0.04 mol) were added consecutively with stirring to isatin 1 (0.04 mol)
or an N-alkylisatin 2-7 in a mixture of water (45 ml) and i-PrOH (30 ml) (or EtOH or MeCN). The mixture was
stirred for 8 h at room temperature and the precipitate was filtered off, and washed (3×25 ml) with i-PrOH (or
EtOH or MeCN). The crystalline product was used for further synthesis without purification. For analytical
purposes, a sample was recrystallized from a suitable solvent to give:
3-Hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one (8), 3-Hydroxy-1-methyl-3-(2-oxo-2-phenyl)indolin-
2-one (9), 1-Ethyl-3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one (10), 3-[2-(2,4-Dichlorophenyl)-2-oxoethyl]-
3-hydroxyindolin-2-one (11), 3-[2-(2,4-Dichlorophenyl)-2-oxoethyl]-3-hydroxy-1-methylindolin-2-one (12),
3-[2-(2,4-Dichlorophenyl)-2-oxoethyl]-1-ethyl-3-hydroxyindolin-2-one (13), 1-Butyl-3-[2-(2,4-dichlorophenyl)-
2-oxoethyl]-3-hydroxyindolin-2-one (14), 3-[2-(2,4-Dichlorophenyl)-2-oxoethyl]-1-hexyl-3-hydroxyindolin-2-one
(15), 3-[2-(2,4-Dichlorophenyl)-2-oxoethyl]-3-hydroxy-1-nonylindolin-2-one (16), and 1-Decyl-3-[2-(2,4-dichloro-
phenyl)-2-oxoethyl]-3-hydroxyindolin-2-one (17) (Table 1).
Preparation of Enones 18-25 (General Method). Dehydration of the corresponding keto alcohols was
carried out by a method analogous to [9] to obtain:
3-(2-Oxo-2-phenylethylidene)-2-indolin-2-one (18), 3-[2-(2,4-Dichlorophenyl)-2-oxoethylidene]-
indolin-2-one (19), 1-Methyl-3-(2-oxo-2-phenylethylidene)indolin-2-one (20), 3-[2-(2,4-Dichlorophenyl)-
2-oxoethylidene]-1-methylindolin-2-one (21), 1-Ethyl-3-(2-oxo-2-phenylethylidene)indolin-2-one (22), 3-[2-(2,4-
Dichlorophenyl)-2-oxoethylidene]-1-ethylindolin-2-one (23), 1-Butyl-3-[2-(2,4-dichlorophenyl)-2-oxoethyl-
idene]indolin-2-one (24), 3-[2-(2,4-Dichlorophenyl)-2-oxoethylidene]-1-hexylindolin-2-one (25), 3-[2-(2,4-
Dichlorophenyl)-2-oxoethylidene]-1-nonylindolin-2-one (26), and 1-Decyl-3-[2-(2,4-dichlorophenyl)-2-oxo-
ethylidene]indolin-2-one (27), (Table 1).
Preparation of Pyrazolinyloxoindoles 28-31 (General Method). A mixture of the initial enone
(0.005 mol) and 98% hydrazine hydrate (0.006 mol) in absolute ethanol (35 ml) was refluxed for 4-8 h until the
reaction was completed (monitored by TLC). The mixture was left overnight, the residue was separated, and
recrystallized from a suitable solvent to give:
5'-Phenyl-2',4'-dihydrospiro[3H-indole-3,3'-[3H]-pyrazol]-2(1H)-one (28), 5'-(2,4-Dichlorophenyl)-
2',4'-dihydrospiro[3H-indole-3,3'-[3H]-pyrazol]-2(1H)-one (29), 5'-(2,4-Dichlorophenyl)-2',4'-dihydrospiro-
[3H-indole-3,3'-[3H]-pyrazol]-1-methyl-2(1H)-one (30), 5'-(2,4-Dichlorophenyl)-2',4'-dihydrospiro[3H-
indol-3,3'-[3H]-pyrazol]-1-ethyl-2(1H)-one (31) (Table 1).
Acetylation of pyrazolinoxoindoles (General Method). Pyridine (0.079g, 0.001 mol) was added to a
suspension of a pyrazolindole (0.005 mol) in Ac2O (7.65 g, 0.0075 mol) and the mixture was heated at 95-100°C
for 5 h. The mixture was cooled to room temperature, water (2 ml) was added, and after stirring for 2.5 h, the
precipitate was filtered off, washed with water (15 ml) and then i-PrOH (2 ml). The residue was dried over
NaOH in vacuum and then recrystallized from a suitable solvent to give:
1,2'-Diacetyl-5'-phenyl-2',4'-dihydrospiro[3H-indole-3,3'-[3H]-pyrazol]-2(1H)-one (32) and 2'-Acetyl-
5'-(2,4-dichlorophenyl)-1-ethyl-2',4'-dihydrospiro[3H-indole-3,3'-[3H]-pyrazol]-2(1H)-one (33) (Table 1).
X-ray crystallographic analysis. For X-ray structural study a monocrystal with prismatic habit was chosen with
linear dimensions 0.1 x 0.2 x 0.2 mm after recrystallization from ethanol. The monoclinic crystals belonged to
space group P21c with unit cell parameters: a =14.532(3), b = 8.334(3), c = 15.872(3) Å, β = 112.75(3)°,
V = 1772.7 Å3, dcalc = 1.302 g/cm3, C20H17N3O3, with Z = 4. To determine and refine the structure 4454
independent reflexions with I ≥ 3σ(I) were used. The structure was determined by the direct method via the
SHELX-93 suite of programs [22]. Refinement was in the anisotropic approximation for C, O, and N atoms.
304

Hydrogen atoms were localized by difference Fourier syntheses and refined in the isotropic approximation.
GOOF(S) = 1.146, the final R factors were R1 = 0.054, wR2 = 0.139.
Complete X-ray crystallographic data can be obtained from F. Z. Macaev.
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