Synthesis and reactions of 1-benzyl-3-haloalkyl-5-chloropyrazoles

Article abstract of DOI:10.1134/S1070428009050108

Synthesized 1-benzyl-3-chloroalkyl-5-chloropyrazoles reacted with indole and pyrrole in DMSO in the presence of alkali to give 3-(heter-1-yl)alkyl- substituted 1-benzyl-5-chloropyrazoles. 1-[(1-Benzyl-5-chloropyrazol-3-yl) methyl]indole reacted regiospeci

Full text of DOI:10.1134/S1070428009050108

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 705−711. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © E.V. Rudyakova, V.A. Savosik, I.T. Evstaf'eva, E.V. Kondrashov, G.G. Levkovskaya, 2009, published in Zhurnal Organicheskoi
Khimii, 2009, Vol. 45, No. 5, pp. 722−727.
Synthesis and Reactions of 1-Benzyl-3-haloalkyl-5-chloropyrazoles
E. V. Rudyakova, V. A. Savosik, I. T. Evstaf'eva, E. V. Kondrashov, and G. G. Levkovskaya
Faworsky Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, 664033 Russia
e-mail: ggl@irioch.irk.ru
Received July 28, 2008
Abstract—Synthesized 1-benzyl-3-chloroalkyl-5-chloropyrazoles reacted with indole and pyrrole in DMSO in the
presence of alkali to give 3-(heter-1-yl)alkyl-substituted 1-benzyl-5-chloropyrazoles. 1-[(1-Benzyl-5-chloropyrazol-
3-yl)methyl]indole reacted regiospecifically with chloroal trifluoromethylsulfonyl- and 4-chlorophenylsulfonyl-
imines providing the products of C-amidotrichloroethylation into the position 3 of the indole ring. {1-[(1-Benzyl-
5-chloropyrazol-3-yl)methyl]indol-3-yl}sulfanylacetic acid was obtained by the reaction of 1-[(1-benzyl-5-
chloropyrazol-3-yl)methyl]-indole with iodine, thiourea, and chloroacetic acid.
DOI: 10.1134/S1070428009050108
The synthesis and chemical transformations of pyr-
azoles attract a wide interest for they are extensively
employed in pharmaceutical industry, agriculture, and in
new materials production. In particular, the halopyrazoles
are key intermediates in the production of light-sensitive
materials, dyes, insecticides, fungicides, herbicides, and
drugs of a wide range of action, including antiphlogistic,
anti-fever, antibacterial etc. activity [1–9].
similarly to the preparation of 5-chloro-3-chloro-methyl-
1-ethylpyrazole [11].
The corresponding ketones Ia–Ic, among them
previously unknown Ib and Ic, were obtained from the
chlorides of haloalkanecarboxylic acids and vinylidene
chloride in the presence of aluminum chloride by
procedure [12].
The structure of haloalkyl 2,2-dichlorovinyl ketones
Ia–Ic and pyrazoles IIa–IIc obtained therefrom was
confirmed by IR and NMR spectra, and their composition,
by elemental analysis (Scheme 1).
In extension of our systematic research aimed at the
purposeful synthesis and the study of chemical properties
of halopyrazoles [10] we synthesized a series of 1-benzyl-
3-haloalkyl-5-chloropyrazoles and established that these
pyrazoles enter into reactions with indole and pyrrole
affording products of N-alkylation of the said heterocycles
in good yields.
The obtained ketones Ia–Ic are light-yellow fluids
distillable in a vacuum and possessing a lacrimator action.
The IR spectra of ketones Ia–Ic contained the
characteristic absorption bands of carbonyl groups, C=C
and =C–H bonds, and also absorption bands of alkyl CH
bonds.
The synthesis of previously unknown 1-benzyl-3-
haloalkyl-5-chloropyrazoles was carried out by treating
haloalkyl 2,2-dichlorovinyl ketones with benzylhydrazine
Scheme 1.
R
O
NNHBn
RCCH CCl2 + H2NNHBn
_
_
N
C
HHlg
H2O
Cl
Ia_Ic
N
R
CH
CCl2
Bn
IIa_IIc
R = CH2Cl (a), CH3CHCl (b), CH3CH2CHBr (c).
705

RUDYAKOVA et al.
706
1H NMR spectrum of compounds Ia–Ic contained
the proton signals of two methylene groups and H4 proton
of the pyrazole ring, doublets of indole protons H2 and
H3, and also the signals of the phenyl protons.
the proton signals from haloalkyl moieties and the signals
13
of vinyl protons. In the C NMR spectra signals were
observed belonging to carbon atoms of methyl and
methylene fragments, of CH=, =CCl2, and C=O groups.
The carbon signal from the CHCl fragment appeared
downfield compared to the analogous signal from CHBr
group.
1
In the H NMR spectrum of compound IV also the
signals were observed from the protons of two methylene
groups, of H4 proton of the pyrazole ring, two signals
from the protons of the pyrrole ring, and also the signals
of the phenyl protons.
The IR spectra of pyrazoles IIa–IIc contained absorp-
tion bands of C=C, C=N bonds, of CH bonds from the
alkyl fragments, and of C4H in the pyrazole ring.
The presence in the pyrazole molecule of chloroethyl
or bromopropyl group complicated the reaction of 3-(halo-
alkyl)-substituted pyrazoles with indole.
The 1H NMR spectra of pyrazoles IIa–IIc are char-
acterised by the presence of the proton signals from the
chloroalkyl and benzyl fragments, and of H4 in the
pyrazole ring. The integral intensity of the signals was
consistent with the assumed structures. In 13C NMR
spectra signals were present of atoms C3, C4, and C5 of
the pyrazole ring, and also of groups CH2Ph and
RCHHlg.
For instance, in the reaction of 1-benzyl-5-chloro-3-
(1-chloroethyl)pyrazole (IIb) with indole under the
conditions analogous to used in the synthesis of compound
III formed a mixture of 1-[1-(1-benzyl-5-chloropyrazol-
3-yl)ethyl]indole (V) with the initial indole in the ratio 4:1
(1H NMR data). The increased reaction time and the
use of excess pyrazole IIb (up to twofold excess) did
not lead to the enhance yield of target product V. We
failed to separate the mixture of the alkylated and initial
indoles, but the formed pyrazoloindole V was char-
acterized by the 1H NMR spectrum.
Aiming at preparation of new polyheterocyclic
ensembles we studied the reactions of 3-(haloalkyl)-
substituted pyrazoles with indole and pyrrole.
1-Benzyl-5-chloro-3-chloromethylpyrazole reacted
with indole and pyrrole in the presence of alkali in DMSO
solution at room temperature under the conditions of the
N-alkylation of indoles [13] resulting in the corresponding
heterocyclic compounds, 1-[(1-benzyl-5-chloropyrazol-3-
yl)methyl]indole (III) and 1-[(1-benzyl-5-chloropyrazol-
3-yl)-methyl]pyrrole (IV) in 75 and 63% yield respec-
tively (Scheme 2).
Yet 1-benzyl-3-(1-bromopropyl)-5-chloropyrazole
(IIc) under the similar conditions did not effect the
N-alkylation of indole, but underwent the dehydrobromina-
tion yielding 1-benzyl-3-(1-propenyl)-5-chloropyrazole
(VI). Under the studied conditions propenylpyrazole VI
formed with a difficultly separable admixture of the initial
pyrazole IIc in a ratio 4:1.
The structure of compounds III and IV was proved
by IR and NMR spectroscopy, their composition was
confirmed by elemental analysis.
We studied the properties of the synthesized indolo-
methylpyrazole III and established that it entered into
reactions with highly electrophilic chloral trifluoromethyl-
sulfonyl- and 4-chlorobenzenesulfonylimines without
catalyst or heating providing in good yields products of
C-amidotrichloroethylation of indole into the position 3
VII and VIII (Scheme 3).
In the IR spectra of compounds III and IV the absorp-
tion bands were observed originating from the aromatic
and heterocyclic fragments and of alkyl CH bonds. The
1H NMR spectrum of substituted indole III contained
Scheme 2.
R2
ClH2C
KOH
DMSO
+
N
N
R2
R1
Cl
N
N
H
R1
Bn
N
Cl
N
IIà
Bn
III, IV
R1, R2 = (CH)4 (III), R1 = R2 = H (IV).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

SYNTHESIS AND REACTIONS OF 1-BENZYL-3-HALOALKYL-5-CHLOROPYRAZOLES
707
Scheme 3.
CCl3
CHNHSO2R
N
N
RSO2N CHCCl3
+
N
N
Cl
Cl
N
N
Bn
Bn
III
VII, VIII
R = CF3 (VII), 4-ClC6H4 (VIII).
Chloral sulfonylimines prepared from the correspond-
ing N,N-dichloroamides and trichloroethylene [14,15]
were brought into the reaction with indolomethylpyrazole
III without isolation of the imines from the reaction
mixture under the conditions previously developed for the
C-amidoalkylation of indoles [16].
the indole ring unambiguously indicating the direction of
the C-amidoalkylation. Besides in the spectra of com-
pounds VII and VIII signals are observed of the coupled
protons of the fragment CH–NH, of protons from CH2
groups, of the indole and aromatic rings.
Indolomethylpyrazole III can be used in the synthesis
of {1-[(1-benzyl-5-chloropyrazol-3-yl)-methyl]indol-3-
yl}sulfanylacetic acid (IX), interesting as a promising
biologically active substance [17–20] or a precursor for
the preparation of such substances (Scheme 4).
We did not find any products of C-amidoalkylation
into the position 4 of the pyrazole ring. This is due to the
lower nucleophilicity of the position 4 of the pyrazole
ring compared to the position 3 of the indole ring, and
evidently also to the steric effect of the bulky methylindole
substituent.
We planned both to introduce the pyrazole ring into
the structure of indolylsulfanylacetic acids and to
investigate the effect of the pyrazole fragment on the
direction of the reaction of compound III with thiourea
and iodine.
The synthesized compounds VII and VIII are light-
pink and light-brown powders.
1
The H NMR spectra of compounds VII and VIII
contain a singlet from the proton in the position 4 of the
pyrazole ring and no proton signal from the position 3 of
The molecule of indolomethylpyrazole III contains
several reaction sites where a halogen atom can be
Scheme 4.
NH2
NH HI
C
S
Cl
Cl
N H2C
NH2
NH2
N H2C
,
I2 KI
N N
+
S
C
N N
Bn
Bn
III
SCH2COOH
SCH2COONa
N H2C
Cl
Cl
NaOH,
ClCH2COOH
N H2C
HCl
N N
N N
Bn
Bn
IX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

RUDYAKOVA et al.
708
introduced: the positions 2 and 3 of the indole ring and
the position 4 of the pyrazole ring. Besides, it is not
possible to exclude a priori the substitution of a chlorine
in the pyrazole ring of compound III for an isothiuronium
fragment under the action of the thiourea.
Yield 15.0 g (80%), bp 104–106°C (20 mm Hg). IR
spectrum, ν, cm–1: 3056 (=C–H), 2986, 2935, 2867
1
(CHalk), 1704 (C=O), 1580 (C=C). H NMR spectrum
(CDCl3), δ, ppm: 1.61 d (3H, CH3, J 6.6 Hz), 4.37 q (1H,
CHCl, J 6.6 Hz), 7.01 s (1H, CH=CCl2). 13C NMR
spectrum, δ, ppm: 19.56 (CH3), 58.49 (CHCl), 122.13
(CH=), 138.96 (CCl2), 189.10 (C=O). Found, %: C 32.44;
H 2.68; Cl 56.79. C5H5Cl3O. Calculated, %: C 32.04;
H 2.69; Cl 56.74.
The reaction of indolomethylpyrazole III with thiourea
and iodine was carried out by the one-pot method we
had developed before without isolation of the isothiuronium
salt from the reaction mixture [21] It was established
that no substitution products in the pyrazole ring formed,
and that the reaction occurred only at the position 3 of
the indole ring.
1-Bromopropyl 2,2-dichlorovinyl ketone (Ic) was
obtained from 18.55 g (0.1 mol) α-bromobutyryl chloride
and 11.63 g (0.12 mol) of vinylidene chloride. Yield 21.0 g
(85%), bp 124–126°C (20 mm Hg). IR spectrum, ν,
cm–1: 3054 (=CH), 2973 2937, 2882 (CHalk), 1697 (C=O),
1572 (C=C). 1H NMR spectrum (CDCl3), δ, ppm: 1.03 t
(3H, CH3, J 7.3 Hz), 2.01 m (2H, CH2, J 6.4, 7.3 Hz),
4.21 t (1H, CHBr, J 6.4 Hz), 6.92 s (1H, CH=CCl2).
13C NMR spectrum, δ, ppm: 11.95 (CH3), 26.67 (CH2),
55.91 (CHBr), 123.00 (CH=), 138.70 (=CCl2), 188.27
(C=O). Found, %: C 29.38; H 2.88; Br 32.55; Cl 28.71.
C6H7BrCl2O. Calculated, %: C 29.30; H 2.87; Br 32.49;
Cl 28.83.
The structure of compound IX was proved by IR and
NMR spectroscopy, its composition was confirmed by
elemental analysis. The IR spectrum contained the
absorption bands of COOH group, of C=N, C=C, =C–H,
and C–H bonds.
1
In the H NMR spectra signals appeared from the
protons in the position 2 of the indole ring and in the
position 4 of the pyrazole ring.
Therefore as a result of the performed research we
carried out the synthesis of 1-benzyl-3-halo-alkyl-5-
chloropyrazoles that were brought into the reactions with
indole and pyrrole; a high reactivity was demonstrated
of the obtained 1-[(1-benzyl-5-chloropyrazol-3-yl)-
methyl]indole in reactions with chloral trifluoromethyl-
and 4-chlorophenylsulfonylimines, and by its reaction with
iodine, thiourea, and monochloroacetic acid a pyr-
azoloindol-3-ylsulfanylacetic acid was obtained.
1-Benzyl-5-chloro-3-chloromethylpyrazole (IIa).
To a solution of 8.67 g (0.05 mol) of ketone Ia in 30 ml of
ethanol was added dropwise 6.10 g (0.05 mol) of benzyl-
hydrazine and 5.06 g (0.05 mol) of triethylamine. The
reaction mixture was boiled for 3 h, cooled, and poured
into water, extracted with ethyl ether, the extract was
dried with CaCl2, the ether was removed in a vacuum.
Yield 9.05 g (75%), mp 28–30°C. IR spectrum, ν, cm–1:
3120, 3050, 3030 (=C–H), 2945 (CHalk), 1590, 1500 (C=N,
C=C). 1H NMR spectrum (CDCl3), δ, ppm: 4.52 s (2H,
CH2Cl), 5.28 s (2H, CH2), 6.30 s (1H, H4), 7.19 d, 7.29 m
(5H, C6H5). 13C NMR spectrum, δ, ppm: 38.98 (CH2Cl),
52.91 (CH2), 104.70 (C4), 127.39, 128.05, 128.78 (C6H5),
135.00 (C5), 149.00 (C3). Found, %: C 54.85; H 4.28;
Cl 29.39; N 11.60. C11H10Cl2N2. Calculated, %: C 54.79;
H 4.18; Cl 29.41; N 11.62.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Specord 75IR from pellets with KBr. 1H and 13C NMR
spectra were registered on a spectrometer Bruker DPX-
400 (at 400.13 and 100.61 MHz respectively), internal
reference HMDS, chemical shifts values were given
relative to TMS, measurements accuracy was 0.01 and
0.02 ppm for 1H and 13C respectively, coupling constants
were determined with the accuracy of 0.1 Hz.
1-Benzyl-5-chloro-3-(1-chloroethyl)pyrazole (IIb)
was obtained similarly from 9.37 g (0.05 mol) of ketone
Ib, 6.10 g (0.05 mol) of benzylhydrazine, and 5.06 g
(0.05 mol) of triethylamine.Yield 10.87 g (86%), bp 130°C
(15 mm Hg). IR spectrum, ν, cm–1: 3141 (CHHt), 3089,
3064, 3032 (=CH), 2981, 2931, 2875 (CHalk), 1514 1496
Chloromethyl 2,2-dichlorovinyl ketone (Ia) and
previously unknown 2,2-dichlorovinyl 1-chloroethyl ketone
(Ib), 1-bromopropyl 2,2-dichlorovinyl ketone (Ic) were
prepared by procedure [12]. Physicochemical constants
of ketone Ia were consistent with the published data [12].
1
(C=N, C=C). H NMR spectrum (CDCl3), δ, ppm:
1.79 d (3H, CH3, J 6.8 Hz), 5.06 q (1H, CHCl, J 6.8 Hz),
5.23 s (2H, CH2), 6.27 s (1H, C4H), 7.21 m (5H, C6H5).
13C NMR spectrum, δ, ppm: 24.59 (CH3), 51.77
(CHCl), 52.70 (CH2), 102.80 (CH4 t), 127.18 (CP3h,5), 127.56
2,2-Dichlorovinyl 1-chloroethyl ketone (Ib) was
obtained from 12.69 (0.1 mol) of α-chloropropionyl
chloride and 11.63 g (0.12 mol) of vinylidene chloride.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

SYNTHESIS AND REACTIONS OF 1-BENZYL-3-HALOALKYL-5-CHLOROPYRAZOLES
709
2,6
(CH5 t), 127.81 (C4Ph), 128.57 (C ), 135.60 (CP1h), 153.70
Cl 13.06; N 15.06. C15H14ClN3. Calculated, %: C 66.30;
H 5.19; Cl 13.05; N 15.46.
Ph
(C4Ht). Found, %: C 56.65; H 4.38; Cl 27.80; N 11.08.
C12H12Cl2N2. Calculated %: C 56.71; H 4.36; Cl 27.90;
N 11.02.
Reaction of 1-benzyl-5-chloro-3-(1-chloroethyl)-
pyrazole (IIb) with indole. The reaction was carried
out as described above for compound III using 2.80 g
(0.011 mol) of pyrazole IIb and 1.17 g (0.01 mol) of indole.
We obtained 2.4 g of a mixture containing according to
1H NMR data 1-[1-(1-benzyl-5-chloropyrazol-3-
yl)ethyl]indole (V) and initial indole in a ratio 4:1.
Compound V. 1H NMR spectrum (DMSO-d6), δ, ppm:
1.87 d (3H, CH3, J 7.1 Hz), 5.26 s (2H, CH2), 5.63 q
(1H, CH, J 7.1 Hz), 5.84 s (1H, H4pyrazole), 6.54 d (1H,
H3indole, J 3.1 Hz), 7.18 d (1H, H2indole, J 3.1 Hz), 7.22 m,
7.32 m, 7.61 m (9H, H4i–n7dole, C6H5).
1-Benzyl-3-(1-bromopropyl)-5-chloropyrazole
(IIc) was obtained similarly from 12.29 g (0.05 mol) of
ketone Ic, 6.10 g (0.05 mol) of benzylhydrazine, and
5.06 g (0.05 mol) of triethylamine. Yield 12.2 g (78%),
bp 146–148°C (5 mm Hg). IR spectrum, ν, cm–1: 3134
(=CHHt), 3089, 3065, 3032 (=CH), 2971, 2934, 2875
1
(CHalk), 1511, 1497 (C=N), (C=C). H NMR spectrum
(CDCl3), δ, ppm: 1.00 t (3H, CH3, J 7.3 Hz), 2.17 m (2H,
CH2, J 7.3, 7.4 Hz), 4.90 t (1H, CHBr, J 7.4 Hz), 5.26 s
(2H, CH2), 6.27 s (1H, C4H), 7.24 m (5H, C6H5).
13C NMR spectrum, δ, ppm: 12.62 (CH3), 32.05 (CH2CH3),
49.12 (CHBr), 52.82 (CH2Ph), 103.50 (C4Ht), 127.19
Reaction of 1-benzyl-3-(1-bromopropyl)-5-
chloropyrazole (IIc) with indole. The reaction was
carried out as described above for compound III using
3.44 g (0.011 mol) of pyrazole IIc, 1.17 g (0.01 mol) of
indole and applying 1.12 g (0.02 mol) of KOH. We
obtained 2.5 g of a mixture containing according to 1H
NMR data compoundÿ VI and initial pyrazole IIc in a
ratio 4:1.
3,5
2,6
(C ), 127.78 (C5Ht), 127.89 (CP4h), 128.67 (C ), 135.74
Ph
Ph
(CP1h), 153.38 (CH3 t). Found, %: C 49.85; H 4.21; Br 25.39;
Cl 11.39; N 8.88. C13H14BrClN2. Calculated %: C 49.95;
H 4.19; Br 25.56; Cl 11.34; N 8.96.
1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]indole
(III). Amixture of 1.2 g (0.03 mol) of NaOH and 5 ml of
DMSO was stirred for 10–20 min, and 1.17 g (0.01 mol)
of indole was added. The mixture was stirred additionally
for 20–30 min, then at cooling to 18–20°C was slowly
added dropwise a solution of 2.65 g (0.011 mol) of
pyrazole IIa in 2 ml of DMSO, and the reaction mixture
was stirred for 8 h at 20–22°C. Then the reaction mixture
was poured into 50 ml of ice water, extracted with ethyl
ether, the extract was dried with MgSO4. The ether was
removed in a vacuum, the residue was recrystallized from
a mixture of ethyl ether and hexane. Yield 2.41 g (75%),
mp 68–71°C. IR spectrum, ν, cm–1: 2850, 2920, 2950
1-Benzyl-3-(1-propenyl)-5-chloropyrazole (VI).
IR spectrum, ν, cm–1: 1664 (C=C), 2851, 2913, 2935, 2962
1
(CHalk), 3032, 3065, 3088, 3134 (=C–H). H NMR
spectrum (CDCl3), δ, ppm: 1.82 d (3H, CH3, J 6.5 Hz),
5.24 s (2H, CH2), 6.15 m (1H, =CHMe), 6.23 s (1H,
H4pyrazole), 6.29 m (1H, =CH), 7.23 m (5H, Ph).
N-(1-{1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]-
indol-3-yl}-2,2,2-trichloroethyl)trifluoromethane-
sulfonamide (VII). To a solution of chloral trifluoro-
methylsulfonylimine obtained from 2.18 g (0.01 mol) of
trifluoromethanesulfonic acid N,N-dichloroamide and
7 ml of trichloroethylene as described in [15] was added
by small portions at stirring 3.22 g of indolomethylpyrazole
III. After 6 h the solvent was removed in a vacuum. The
residue was washed with hot water, dried, twice recrystal-
lized from hexane, and was dried in a vacuum. Yield
4.18 g (78%), mp 63°C. IR spectrum, ν, cm–1: 1550, 1610
(C=N, C=C), 2950 (CHalk), 3035 (=CH), 3280 (NH).
1H NMR spectrum (CDCl3), δ, ppm: 5.22 s (2H, CH2),
5.25 s (2H, CH2), 5.59 s (1H, CH–CCl3), 5.85 s (1H,
H4pyrazole), 6.95 br.s (1H, NH), 7.12–7.38 m (8H, C6H5,
1
(CHalk), 3130 (=C–H). H NMR spectrum (CDCl3), δ,
ppm: 5.27 s (2H, CH2), 5.30 s (2H, CH2), 5.94 s (1H,
Hp4yrazole), 6.54 d (1H, Hi3ndole, J 3.1 Hz), 7.18 d (1H, Hi2ndole
,
4,7
J 3.1 Hz), 7.22 m, 7.32 m (7H, H
, C6H5), 7.40 d
indole
(1H, H5indole, J 7.8 Hz), 7.65 d (1H, H6indole, J 7.8 Hz).
Found, %: C 69.00; H 5.19; Cl 13.06; N 10.86.
C19H16ClN3. Calculated, %: C 71.01; H 5.02; Cl 13.08;
N 10.89.
1-[(1-Benzyl-5-chloropyrazole-3-yl)methyl]-
pyrrole (IV) was obtained from 2.65 g (0.011 mol) of
pyrazole IIa and 0.68 g (0.01 mol) of pyrrole in 1.71 g
(63%) yield, mp 80–85°C. IR spectrum, ν, cm–1: 2850,
13
3Hindole), 7.41 C (1H, H2indole), 7.67 d (1H, H7indole). C
1
NMR spectrum, δ, ppm: 44.71 (CH2), 52.84 (CH2), 66.53
(CH–NH), 101.47 (CCl3), 103.78 (C4pyrazole), 109.06
(C3indole), 110.25 (Ci4ndole), 119.08 (Ci7ndole), 119.25 q (CF3,
1JC–F 321.4 Hz), 120.92 (Ci5ndole), 122.86 (C6indole), 127.34
2920, 2950 (CHalk), 3130 (=C–H). H NMR spectrum
(CDCl3), δ, ppm: 4.92 s (2H, CH2), 5.27 s (2H, CH2),
6.00 s (1H, H4pyrazole), 6.14 s (2H, H
), 6.69 C (2H,
3,4
pyrrole
2,5
H
), 7.23 m (5H, Ph). Found, %: C 67.01; H 5.29;
pyrrole
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

RUDYAKOVA et al.
710
(C2,6), 127.41 (C
), 127.74 (C2indole), 128.21 (CP4h),
1H NMR spectrum (DMSO-d6), δ, ppm: 3.18 s (2H,
4a
indole
Ph
128.54 (C5pyrazole), 128.89 (CP3h,5), 135.63 (CP1h), 135.71
(C7inadole), 148.43 (Cp3yrazole). Found, %: C 44.10; H 2.80;
Cl 23.58; N 9.30; S 5.30. C22H17Cl4F3N4O2S. Calculated,
%: C 44.02; H 2.85; Cl 23.62; N 9.33; S 5.34.
CH2), 5.08 s (2H, CH2), 5.11 s (2H, CH2), 6.04 s (1H,
H4pyrazole), 6.92 m, 7.07 m (9H, 4Hindole, C6H5), 7.43 (1H,
H2indole). Found, %: C 58.95; H 4.43; Cl 8.11; N 9.78;
S 14.71. C21H19ClN3O2S. Calculated, %: C 58.87; H 4.47;
Cl 8.17; N 9.81; S 14.94.
N-(1-{1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]-
indol-3-yl}-2,2,2-trichloroethyl)-4-chlorobenzene-
sulfonamide (VIII) was obtained from 3.22 g (0.01 mol)
of indolomethylpyrazole III and chloral 4-chloro-
phenylsulfonylimine obtained from 2.61 g (0.01 mol) of
N,N-dichloro-4-chlorobenzenesulfonamide and 7 ml of
trichloroethylene as described in [14]. Yield 4.76 g (75%),
mp 197–199°C. IR spectrum, ν, cm–1: 1545, 1590 (C=N,
C=C), 2850, 2915, 2950 (CHalk), 3020, 3050, 3125 (=CH)
REFERENCES
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1
3255 (NH). H NMR spectrum (DMSO-d6), δ, ppm:
5.50 d (2H, CH2), 5.62 s (1H, CH–CCl3), 5.66 s (2H,
CH2), 6.50 s (1H, H4pyrazole), 7.17–7.78 m (13H, C6H5,
C6H4, 4Hindole), 7.90 s (1H, H2indole), 9.36 s (1H, NH).
13C NMR spectrum, δ, ppm: 44.07 (CH2), 52.57 (CH2),
65.74 (CH), 103.09 (CCl3), 104.52 (C4pyrazole), 108.88
(Ci3ndole), 110.37 (Ci4ndole), 118.87 (Ci7ndole), 120.24 (Ci5ndole),
122.02 (Ci6ndole), 127.32 (C
128.29, 128.48, 128.56, 129.14, 129.38, 135.04, 136.72,
137.25, 139.24, 148.88 (C3pyrazole). Found, %: C 50.50;
H 3.35; Cl 27.73; N 8.78; S 4.90. C27H21Cl5N4O2S.
Calculated, %: C 50.45; H 3.29; Cl 27.58; N 8.72; S 4.99.
), 127.58, 127.92 (Cp5yrazole),
4a
indole
{1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]indol-
3-yl}sulfanylacetic acid (IX). To a solution of 3.22 g
(0.01 mol) of indolomethylpyrazole III and 1.52 g
(0.02 mol) of thiourea in 30 ml of ethanol was added
dropwise in an argon flow within 30 min a solution of
2.53 g (0.01 mol) of iodine and 1.66 g (0.01 mol) of
potassium iodide in 20 ml of 50% C2H5OH. The reaction
mixture was heated at 30–40°C for 3 h, then was added
dropwise 0.50 g (0.01 mol) of hydrazine hydrate and
slowly was added a solution of 2.00 g (0.05 mol) of NaOH
in 5 ml of water and 1.42 g (0.015 mol) of monochloro-
acetic acid in 5 ml of water. The reaction mixture was
heated on a boiling water bath for 2 h at pH no less than
9. On completion of the reaction the ethanol was
evaporated, the separated precipitate was dissolved at
heating in water with activated carbon added, the solution
was kept for 30–60 min, then it was filtered, and the
filtrate was acidified with 10% HCl to pH 2–4, then it
was maintained at 5°C at least 12 h till the product
completely settled and crystallized. The precipitate was
filtered off and dried in air. Yield 2.80 g (80%), mp 106–
110°C. IR spectrum, ν, cm–1: 1580, 1610 (C=N, C=C),
1700 (C=O), 2950 (CH2), 3050, 3120 (=CH), 3400 (OH).
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SYNTHESIS AND REACTIONS OF 1-BENZYL-3-HALOALKYL-5-CHLOROPYRAZOLES
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009