4-Functionally-substituted 3-heterylpyrazoles: XV. 3-Aryl(heteryl)-1- phenyl-4-pyrazolylmethylamines and heterocumulenes obtained therefrom

Article abstract of DOI:10.1007/s11178-005-0150-x

By reduction of 3-aryl(heteryl)-1-phenyl-4-azidomethyl-pyrazoles in the presence of Raney nickel or by hydrazinolysis of N-[3-aryl(heteryl)-1-phenyl-4- pyrazolylmethyl]phthalimides 4-pyrazolylmethylamines were obtained that in reaction with bis(trichloromethyl) carbonate afforded 3-aryl-(heteryl)-1-phenyl- 4-pyrazolylmethyl isocyanates, and with carbon disulfide furnished 3-aryl-(heteryl)-1-phenyl-4-pyrazolylmethyl isothiocyanates. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-005-0150-x

Russian Journal of Organic Chemistry, Vol. 41, No. 2, 2005, pp. 238-242. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 2, 2005,
pp. 247-251.
Original Russian Text Copyright Ó 2005 by Bratenko, Panimarchuk, Mel’nichenko, Vovk.
4-Functionally-substituted 3-Heterylpyrazoles:
XV.* 3-Aryl(heteryl)-1-phenyl-4-pyrazolylmethylamines
and Heterocumulenes Obtained Therefrom
M.K. Bratenko1, O.I. Panimarchuk1, N.V.Mel'nichenko2, and M.V.Vovk2
1Bukovinskaya State Medical Academy, Chernovtsy, 58000 Ukraine
chornous@chv.ukrpack.net
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, 02094 Ukraine
Receved June 22, 2004
Abstract—By reduction of 3-aryl(heteryl)-1-phenyl-4-azidomethyl-pyrazoles in the presence of Raney nickel or
by hydrazinolysis of N-[3-aryl(heteryl)-1-phenyl-4-pyrazolylmethyl]phthalimides 4-pyrazolylmethylamines were
obtained that in reaction with bis(trichloromethyl) carbonate afforded 3-aryl-(heteryl)-1-phenyl-4-pyrazolylmethyl
isocyanates, and with carbon disulfide furnished 3-aryl-(heteryl)-1-phenyl-4-pyrazolylmethyl isothiocyanates.
composition was proved by elemental analysis, and the
structure by H NMR spectra. The specific feature of
In the previous paper [1] we described the synthesis
and reactions with electrophilic reagents of new type
secondary amines, N-benzyl-N-(4-pyrazolylmethyl)-
amines. In extension of this research we report here on
the synthesis and some reactions of previously virtually
unknown [2] heterocyclic analogs of benzylamine, 4-pyr-
azolyl-methylamines. The latter look promising for
purposeful creation of synthetic databases of potentially
bioactive compounds.
1
these spectra was appearance of a singlet in the region
3.83–3.88 ppm belonging to CH2 group evidencing fast
exchange of the protons of the NH2 group that we failed
to identify since their signal coincided with the resonance
of water present in the DMSO-d6 (2.8–3.1ppm). In the
1H NMR spectra of amines Va, Vb hydrochlorides
registered under similar conditions the protons of CH2
and NH3+ groups appeared as multiplets whose centers
were located respectively at 4.09(4.07) and 8.80(8.78)
ppm indicating the absence or significant deceleration of
NH protons exchange in these salts
Two preparatively convenient synthetic procedures for
preparation of the target substances were developed, both
using 4-chloromethylpyrazoles we had described earlier
[3]. The first procedure (a) involves conversion of
4-chloromethylpyrazoles Ia–Ih effected by sodium azide
in DMSO solution giving new functional derivatives,
4-azido-methyl-pyrazoles IIa–IIh whose structure was
confirmed by IR and 1H NMR spectra. The reduction of
compounds IIa–IIh with the use of Raney nickel in
2-propanol solution afforded 4-pyrazolyl-methylamines
IIIa–IIIh in 75–90% yields.
From 4-pyrazolylmethylamines we prepared both
previously unknown 4-isothiocyanato-methylpyrazoles and
the compounds we had previously obtained from
4-chloromethylpyrazoles and sodium thiocyanate [5]. It
is important that although in the recent 25–30 years the
chemistry of organic isothiocyanates has been extensively
developed [6] in the series of five-membered nitrogen-
containing heterylmethyl isothiocyanates only few
representatives of indolyl-3-methyl isocyanates [7],
pyrazolidinyl-3-methyl isocyanates [8], and tetrazolyl-1-
methyl isocyanates [9] have been synthesized.
By the second procedure (b) the target amines IIIa–
IIIh were synthesized in about similar yields by Gabriel
reaction [4]. To this end 4-chloromethylpyrazoles Ia–Ih
were brought into reaction with potassium phthalimide,
and the resulting N-(4-pyrazolyl)methylphthalimides IVa–
IVh obtained in nearly quantitative yield were subjected
to hydrazinolysis in ethanol (Scheme 1).
As known, the main preparation method for
isocyanates is reaction of amines and their salts with
phosgene [10]. We showed that the conversion of amines
IIIa, IIIf–IIIh into the corresponding 4-isocyanato-
methylpyrazoles VIa–VId was successfully performed
by applying instead of phosgene the commonly used
3-Aryl(heteryl)-1-phenyl-4-pyrazolylmethylamines
IIIa–IIIh are low-melting crystalline substances whose
* For communication XIV see [1].
1070-4280/05/4102-0238Ó2005 Pleiades Publishing, Inc.

4-FUNCTIONALLY-SUBSTITUTED 3-HETERYLPYRAZOLES: XV.
239
Scheme 1.
&+ 1
1D1
$U
1LꢀRIꢀ5HQH\
D
1
1
&+ &O
3K
&+ 1+
1
,,D ,,K
$U
$U
1
2
1
1
1
,D ,K
3K
2
3K
,,,D ,,,K
1+ 1+
.1
2
$U
E
2
1
1
3K
,9D ,9K
I–IV,Ar = Ph(a), 4-FC6H4(b), 4-ClC6H4(c), 3-BrC6H4(d), 4-BrC6H4(e), 4-MeC6H4(f), 4-MeOC6H4(g), 5-chloro-2-thienyl(h).
nowadays bis(trichloromethyl) carbonate (triphosgene)
[11]. The resulting isocyanates VIa and VIb are viscous
oily fluids distillable in a high vacuum. Compounds VIc
and VId we failed to purify by distillation and identified
them in urea VIIa and VIIb form.
Compound IIc. Yield 70%, mp 87–89°C. IR spectrum,
–1
cm : 2165 (N3). 1H NMR spectrum (DMSO-d6), d,
ppm: 4.49 s (2H, CH2), 7.31–7.51 m (5Harom), 7.76 d
(2Harom, J 7.9 Hz), 7.86 d (2Harom, J 7.8 Hz), 8.63 s (1H,
H5). Found, %: C 62.30; H 4.01; N 22.84. C16H12ClN5.
Calculated, %: C 62.04; H 3.90; N 22.61.
4-Isothiocyanatomethylpyrazoles (VIIIa–VIIIb)
were sinthesized form amines IIIa, IIIb, IIIg with the
use of carbon disulfide [12], and they were isolated in
a pure state that had not succeeded before [5].
Compound IId. Yield 68%, mp 71–72°C. IR spectrum,
–1
cm : 2170 (N3). 1H NMR spectrum (DMSO-d6), d,
Scheme 2.
2
&
&+ 1&2
EXPERIMENTAL
ꢀꢁꢂꢃ&O &
&&O
$U
2
2
IR spectra of compounds were recorded on UR-20
,,,Dꢀꢁ,,,I
1
1
1
instrument from KBr pellets. H NMR spectra were
3K
registered on a spectrometer Varian-Gemini (300 MHz),
internal reference TMS.
9,D 9,G
2
4-Azidomethyl-3-aryl(heteryl)-1-phenylpyrazoles
IIa–IIh. Amixture of 10 mmol of 4-chloromethylpyrazole
Ia–Ih and 1.3 g (20 mmol) of sodium azide in 20 ml of
DMSO was heated for 3 h at 80°C, then cooled, and
poured into 100 ml of water. The separated precipitate
was filtered off, washed with water, with 50% aqueous
ethanol, and dried. Compound IIa. Yield 73%, mp 82–
84°C. IR spectrum, cm : 2170 (N3). H NMR spectrum
(DMSO-d6), d, ppm: 4.51 s (2H, CH2), 7.33–7.49 m
(6Harom), 7.78–7.84 m (4Harom), 8.64 s (1H, H5). Found,
%: C 69.50; H 4.86; N 25.63. C16H13N5. Calculated, %:
C 69.80; H 4.76; N 25.44.
&+
1+ & 1+ 5
$U
51+
1
1
3K
9,,Dꢀꢁ9,,E
VI,Ar = Ph(a), 4-MeC6H4(b), 4-MeOC6H4(c), 5-chloro-2-
thienyl (d); VII, R = 4-ClC6H4, Ar = 4-MeOC6H4 (a),
5-chloro-2- thienyl (b). VIII, Ar = Ph(a), 4-MeC6H4(b),
4-MeOC6H4(c).
–1
1
Scheme 3.
&+ 1&6
$U
Compound IIb. Yield 80%, mp 59–60°C. IR spectrum,
&6 ꢀ(W 1ꢁꢀ$F&O
–1
cm : 2170 (N3). 1H NMR spectrum (DMSO-d6), d, ppm:
,,,Dꢀꢁ,,,Iꢀꢁ,,,J
1
1
4.50 s (2H, CH2), 7.26–7.86 m (9Harom), 8.66 s (1H, H5).
Found, %: C 65.27; H 4.15; N 23.99. C16H12FN5.
Calculated, %: C 65.52; H 4.12; N 23.88.
3K
9,,,D 9,,,F
VIII,Ar = Ph(a), 4-MeC6H4 (b), 4-MeOC6H4 (c).
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 2 2005

240
BRATENKO et al.
ppm: 4.48 s (2H, CH2), 7.24–7.81 m (9Harom), 8.65 s (1H,
H5). Found, %: C 54.00; H 3.49; N 19.90. C16H12BrN5.
Calculated, %: C 54.26; H 3.41; N 19.77.
N 10.29. C24H16FN3O2. Calculated, %: C 72.54; H 4.06;
N 10.52.
Compound IVs. Yield 98%, mp 172–173°C. IR
–1
1
spectrum, cm : 1680, 1705, 1755 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 4.88 s (2H, CH2), 7.26 t
(1Harom, J 7.7 Hz), 7.44–7.53 m (4Harom), 7.79–7.88 m
(8Harom), 8.36 s (1H, H5). Found, %: C 69.34; H 3.83;
N 10.24. C24H16ClN3O2. Calculated , %: C 69.65; H 3.90;
N 10.15.
Compound IIe. Yield 86%, mp 95–98°C. IR spectrum,
–1
cm : 2175 (N3). 1H NMR spectrum (DMSO-d6), d, ppm:
4.49 s (2H, CH2), 7.30 t (1Harom, J 7.7 Hz), 7.49 t (2Harom
J 7.9 Hz), 7.62 d (2Harom, J 7.9 Hz), 7.70 d (2Harom
,
,
J 7.8 Hz), 7.86 t (2Harom, J 7.9 Hz), 8.62 s (1H, H5).
Found, %: C 54.02; H 3.53; N 19.89. C16H12BrN5.
Calculated, %: C 54.26; H 3.41; N 19.77.
Compound IVd. Yield 96%, mp 206–207°C. IR
–1
1
spectrum, cm : 1675, 1695, 1745 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 4.88 s (2H, CH2), 7.27 t
(1Harom, J 7.7 Hz), 7.44–7.97 m (12Harom), 8.42 s (1H,
H5). Found, %: C 62.64; H 3.78; N 9.28. C24H16BrN3O2.
Calculated, %: C 62.90; H 3.52; N 9.17.
Compound IIf. Yield 87%, mp 65–66°C. IR spectrum,
–1
cm : 2165 (N3). 1H NMR spectrum (DMSO-d6), d, ppm:
2.37 s (3H, CH3), 4.50 s (2H, CH2), 7.22–7.30 m
(3Harom), 7.44 t (2Harom, J 7.7 Hz), 7.64 d (2Harom
,
J 7.8 Hz), 7.80 d (2Harom, J 7.8 Hz), 8.67 s (1H, H5).
Found, %: C 70.27; H 5.13; N 24.00. C17H15N5.
Calculated, %: C 70.57; H 5.23; N 24.20.
Compound IVe. Yield 89%, mp 187–188°C. IR
–1
1
spectrum, cm : 1685, 1695, 1745 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 4.87 s (2H, CH2), 7.26 t
(1Harom, J 7.8 Hz), 7.39–7.84 m (12Harom), 8.40 s (1H,
H5). Found, %: C 63.27; H 3.29; N 9.44. C24H16BrN3O2.
Calculated, %: C 62.90; H 3.52; N 9.17.
Compound IIg. Yield 75%, mp 61–62°C. IR spectrum,
–1
cm : 2170 (N3). 1H NMR spectrum (DMSO-d6), d, ppm:
3.88 s (3H, CH3O), 4.48 s (2H, CH2), 7.08 d (2Harom
J 8.0 Hz), 7.25–7.30 m (3Harom), 7.42 t (2Harom
J 7.9 Hz), 7.80 d (2Harom, J 8.0 Hz), 8.64 s (1H, H5).
Found, %: C 66.52; H 5.05; N 22.80. C17H15N5O.
Calculated, %: C 66.80; H 4.95; N 22.94.
,
,
Compound IVf. Yield 90%, mp 174–175°C. IR
–1
1
spectrum, cm : 1680, 1705, 1755 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 2.41 s (3H, CH3), 4.87 C
(2H, CH2), 7.26–7.31 m (3Harom), 7.43 t (2Harom
,
Compound IIh. Yield 69%, mp 90–92°C. IR spectrum,
J 7.7 Hz), 7.67 d (2Harom, J 7.8 Hz), 7.81–7.94 m (6Harom),
8.31 s (1H, H5). Found, %: C 76.69; H 5.02; N 10.40.
C25H19N3O2. Calculated, %: C 76.32; H 4.87; N 10.68.
–1
cm : 2170 (N3). 1H NMR spectrum (DMSO-d6), d, ppm:
4.48 s (2H, CH2), 6.92 d (1Harom, J 6.2 Hz), 7.28–7.73 m
(6Harom), 8.63 s (1H, H5). Found, %: C 53.00; H 3.04;
N 22.02. C14H10ClN5S. Calculated, %: C 53.25; H 3.19;
N 22.18.
Compound IVg. Yield 88%, mp 193–194°C. IR
–1
1
spectrum, cm : 1680, 1700, 1750 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 3.84 s (3H, CH3O),
4.87 C (2H, CH2), 7.09 d (2Harom, J 8.0 Hz), 7.25–
7.30 m (3Harom), 7.42 t (2Harom, J 7.8 Hz), 7.80–7.96 m
(6Harom), 8.33 s (1H, H5). Found, %: C 73.11; H 4.54;
N 10.21. C25H19N3O3. Calculated, %: C 73.44; H 4.68;
N 10.26.
N-[3-Aryl(heteryl)-1-phenyl-4-pyrazolylmethyl]-
phthalimides IVa–IVh. A mixture of 20 mmol of
4-chloromethylpyrazole Ia–Ih and 3.7 g (20 mmol) of
potassium phthalimide in 15 ml of DMF was boiled for
3 h, and on cooling poured into 100 ml of water. The
separated precipitate was filtered off, dried, and crystal-
lized from a mixture dioxane–ethanol, 1:1.
Compound IVh. Yield 90%, mp 198–200°C. IR
–1
1
spectrum, cm : 1675, 1700, 1745 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 4.85 s (2H, CH2), 6.92 d
(1Harom, J 6.0 Hz), 7.27–7.50 m (4Harom), 7.79–7.88 m
(6Harom), 8.38 s (1H, H5). Found, %: C 63.25; H 3.20;
N 10.18. C22H14ClN3O2S. Calculated, %: C 62.93;
H 3.36; N 10.01.
Compound IVa. Yield 94%, mp 175–176°C. IR
–1
1
spectrum, cm : 1680, 1700, 1755 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 4.86 s (2H, CH2), 7.26 t
(1Harom, J 7.9 Hz), 7.54–7.82 m (11Harom), 8.38 s (1H,
H5). Found, %: C 75.72; H 4.38; N 10.78. C24H17N3O2.
Calculated, %: C 75.98; H 4.52; N 11.07.
3-Aryl(heteryl)-1-phenyl-4-pyrazolylmethyl-
amines IIIa–IIIh. a. To a dispersion of Raney nickel
prepared from 1 g of nickel-aluminum alloy [13] in 10 ml
of 2-propanol was added 4 mmol of 4-azidomethylpyrazole
IIa–IIh, and the mixture was heated for 1 h at 60°C.
The nitrogen liberation observed ended within 0.5 h. On
Compound IVb. Yield 95%, mp 159–160°C. IR
–1
1
spectrum, cm : 1685, 1700, 1750 (C=O). H NMR
spectrum (DMSO-d6), d, ppm: 4.85 s (2H, CH2), 7.25 t
(3Harom, J 8.0 Hz), 7.43 t (2Harom, J 7.9 Hz), 7.80–7.85 m
(8Harom), 8.38 s (1H, H5). Found, %: C 72.45; H 4.18;
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4-FUNCTIONALLY-SUBSTITUTED 3-HETERYLPYRAZOLES: XV.
241
cooling the precipitate was filtered off, the filtrate was
evaporated to afford an oily residue that crystallized within
5–10 days.
(3H, CH3O), 3.88 s (2H, CH2), 7.14 d (2Harom, J 8.0 Hz),
7.23–7.28 m (3Harom), 7.44 t (2Harom, J 7.8 Hz), 7.82 d
(2Harom, J 8.0 Hz), 8.37 s (1H, H5). Found, %: C 72.95;
H 6.01; N 15.25. C17H17N3O. Calculated, %: C 73.10;
H 6.13; N 15.04.
b. To a boiling mixture of 13mmol of compound IVa–
IVh and 1.5 g of 60% hydrazine hydrate was added within
2 h 40 ml of water, then 10 ml of HCl, and the heating
was continued for 2 h more. The mixture obtained was
filtered while hot. On cooling to the filtrate was added
30 ml of 20% NaOH solution, the organic layer was
extracted with 60 ml of benzene and dried over anhydrous
sodium sulfate. On evaporating the solvent an oily residue
was obtained that crystallized within 5–10 days.
Compound IIIh. Yield 82% (a), 75% (b), mp 52–54°C.
1H NMR spectrum (DMSO-d6), d, ppm: 3.86 s (2H,
CH2), 6.94 d (1Harom, J 6.3 Hz), 7.25–7.73 m (4Harom),
7.75 d (2Harom, J 7.8 Hz), 8.25 s (1H, H5). Found, %:
C 57.80; H 4.05; N 14.65. C14H12ClN3S. Calculated, %:
C 58.03; H 4.17; N 14.50.
3-Aryl(heteryl)-1-phenyl-4-pyrazolylmethyl-
amines hydrochlorides Va and Vb. To 2 mmol of amine
IIIa and IIIb was added 3 ml of concn. HCl, in 1 h 5 ml
of water was added, the precipitate was filtered off and
dried in air.
Compound IIIa. Yield 88% (a), 85% (b), mp 52–
1
54°C. H NMR spectrum (DMSO-d6), d, ppm: 3.85 s
(2H, CH2), 7.28–7.46 m (6Harom), 7.80–7.85 m (4Harom),
8.44 s (1H, H5). Found, %: C 76.85; H 6.25; N 16.67.
C16H15N3. Calculated, %: C 77.08; H 6.06; N 16.89.
1,3-Diphenyl-4-pyrazolylmethylamine hydro-
Compound IIIb. Yield 85% (a), 87% (b), mp 57–
1
chloride (Va). Yield 88%, mp 234–237°C. H NMR
1
59°C. H NMR spectrum (DMSO-d6), d, ppm: 3.83 s
spectrum (DMSO-d6), d, ppm: 4.09 m (2H, CH2), 7.32–
(2H, CH2), 7.19–7.27 m (3Harom), 7.49 t (2Harom
,
7.83 m (10Harom), 8.80 m (3H, NH3 ), 8.89 s (1H, H5).
+
J 8.0 Hz), 7.80–7.88 m (4Harom), 8.44 s (1H, H5). Found,
%: C 72.15; H 5.20; N 15.94. C16H14FN3. Calculated,
%: C 71.89; H 5.28; N 15.72.
Found, %: C 67.65; H 5.32; N 14.39. C16H16ClN3.
Calculated, %: C 67.75; H 5.64; N 14.70.
1-Phenyl-3-(4-fluorophenyl)-4-pyrazolyl-
methylamine hydrochloride (Vb). Yield 95%, mp 242–
244°C. 1H NMR spectrum (DMSO-d6), d, ppm: 4.07 m
(2H, CH2), 7.23–7.31 m (3Harom), 7.50 t (2Harom), 7.73–
Compound IIIc. Yield 90% (a), 89% (b), mp 62–
64°C. 1H NMR spectrum (DMSO-d6), d, ppm: 3.87 s
(2H, CH2), 7.27 t (1Harom, J 7.7 Hz), 7.42–7.49 m
(4Harom), 7.83–7.88 m (4Harom), 8.36 s (1H, H5). Found,
%: C 76.49; H 5.14; N 14.82. C16H14ClN3. Calculated,
%: C 76.72; H 4.97; N 14.81.
7.82 m (4Harom), 8.78 m (3H, NH3 ), 8.88 s (1H, H5).
+
Found, %: C 62.82; H 5.29; N 14.12. C16H15FClN3.
Calculated, %: C 63.26; H 4.98; N 13.83.
Compound IIId. Yield 84% (a), 91% (b), mp 86–
3-Aryl(heteryl)-4-isocyanatopyrazoles VIa–VId
and N-[3-aryl(heteryl)-1-phenyl-4-pyrazolylmethyl]-
ureas VIIa and VIIb. To a solution of 0.4 g (1.33 mmol)
of triphosgene in 30 ml of toluene (with amines IIIa,
IIIf, IIIg) or xylene (with amine IIIh) at 0°C while stirring
was added dropwise a mixture of 4 mmol of amine IIIa,
IIIf–IIIh and 0.8 g (8 mmol) of triethylamine in 15 ml of
an appropriate solvent. The reaction mixture was stirred
at constant temperature for 1 h, and then it was heated
at reflux for a required period: amine IIIa, 5 h; IIIf, 6 h;
amine IIIg, 12 h; and amine IIIh, 12 h. The reaction
mixture was cooled to room temperature, the precipitate
of triethylamine hydrochloride was filtered off, the filtrate
was evaporated, and the residue was either distilled in
a vacuum (for compounds VIa and VIb) or dissolved in
5 ml of acetonitrile (for compounds VIc, VId), to the
solution 0.51g (4 mmol) of p-chloroaniline was added,
and the mixture was left standing for 24 h. The formed
precipitate of compounds VIIa and VIIb was filtered
off and crystallized from a mixture ethanol–dioxane, 1:3.
1
89°C. H NMR spectrum (DMSO-d6), d, ppm: 3.86 s
(2H, CH2), 7.27–7.86 m (9Harom), 8.37 s (1H, H5). Found,
%: C 58.20; H 4.51; N 11.93. C16H14BrN3. Calculated,
%: C 58.55; H 4.30; N 12.18.
Compound IIIe. Yield 83% (a), 82% (b), mp 93–
1
94°C. H NMR spectrum (DMSO-d6), d, ppm: 3.85 s
(2H, CH2), 7.27 t (1Harom, J 7.7 Hz), 7.48–7.89 m
(8Harom), 8.40 s (1H, H5). Found, %: C 58.31; H 4.44;
N 12.25. C16H14BrN3. Calculated, %: C 58.55; H 4.30;
N 12.18.
Compound IIIf. Yield 78% (a), 80% (b), mp 80–
1
82°C. H NMR spectrum (DMSO-d6), d, ppm: 2.39 s
(3H, CH3), 3.88 s (2H, CH2), 7.25–7.31 m (3Harom),
7.47 t (2Harom, J 7.7 Hz), 7.69 d (2Harom, J 7.8 Hz),
7.83 d (2Harom, J 7.8 Hz), 8.35 s (1H, H5). Found, %:
C 77.29; H 6.36; N 16.22. C17H17N3. Calculated, %:
C 77.54; H 6.51; N 15.96.
Compound IIIg. Yield 75% (a), 79% (b), mp 78–
80°C. 1H NMR spectrum (DMSO-d6), d, ppm: 3.82 s
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 2 2005

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BRATENKO et al.
4-IsocyanatOmethyl-1,3-diphenylpyrazole (VIa).
Yield 55%, bp 130–133°C (0.03 mm Hg). IR spectrum
4.78 s (2H, CH2), 7.30–7.52 m (6Harom), 7.62–7.75 m
(4Harom), 8.07 s (1H, H5). Found, %: C 70.44; H 4.47;
N 14.63. C17H13N3S. Calculated, %: C 70.08; H 4.50;
N 14.42.
–1
1
(CH2Cl2), cm : 2250 (NCO). H NMR spectrum
(CDCl3), d, ppm: 4.59 s (2H, CH2), 7.32–7.53 m (6Harom),
7.73–7.80 m (4Harom), 8.03 s (1H, H5). Found, %:
C 73.74; H 4.99; N 15.02. C17H13N3O. Calculated, %:
C 74.16; H 4.76; N 15.26.
4-Isothiocyanatomethyl-3-(4-tolyl)-1-phenyl-
pyrazole (VIIIb). Yield 44%, mp 99–100°C. IR spectrum
–1
1
(CH2Cl2), cm : 2065 (NCS). H NMR spectrum
(CDCl3), d, ppm: 2.40 s (3H, CH3), 4.82 m (2H, CH2),
7.18–7.29 m (3Harom), 7.40 t (2Harom, J 7.8 Hz), 7.66 d
(2Harom, J 7.8 Hz), 7.78 d (2Harom, J 7.8 Hz), 8.10 s (1H,
H5). Found, %: C 71.27; H 4.63; N 14.05. C18H15N3S.
Calculated, %: C 70.79; H 4.95; N 13.76.
4-IsocyanatOmethyl-3-(4-tolyl)-1-phenylpyrazole
(VIb). Yield 52%, bp 180–184°C (0.03 mm Hg). IR
–1
1
spectrum (CH2Cl2), cm : 2250 (NCO). H NMR
spectrum (CDCl3), d, ppm: 2.42 s (3H, CH3), 4.57 m
(2H, CH2), 7.26–7.31 m (3Harom), 7.47 t (2Harom
,
,
J 7.9 Hz), 7.60 d (2Harom, J 7.9 Hz), 7.74 d (2Harom
4-Isothiocyanatomethyl-3-(4-methoxyphenyl)-1-
J
7.9 Hz), 8.01 s (1H, H5). Found, %
:
C 75.13; H 5.47;
phenylpyrazole (VIIIc). Yield 47%, mp 83–86°C. IR
N 14.20. C18H15N3O. Calculated, %: C 74.72; H 5.23;
N 14.52.
–1
1
spectrum (CH2Cl2), cm : 2060 (NCS). H NMR
spectrum (CDCl3), d, ppm: 3.86 s (3H, CH3O), 4.80 m
(2H, CH2), 6.97 d (2Harom, J 8.0 Hz), 7.26–7.45 m
N-[3-(4-Methoxyphenyl)-1-phenyl-4-pyrazolyl-
methyl]-N'-(4-chlorophenyl)urea (VIIa). Yield 58%,
(3Harom), 7.62 d (2Harom, J 8.0 Hz), 7.73 d (2Harom
,
1
J 7.9 Hz), 8.13 s (1H, H5). Found, %: C 67.01; H 4.85;
N 12.75. C18H15N3OS. Calculated, %: C 67.27; H 4.70;
N 13.07.
mp 246–248°C. H NMR spectrum (DMSO-d6), d, ppm:
3.82 s (3H, CH3O), 4.36 d (2H, CH2, J 3.4 Hz), 6.44 t
(1H, NH, J 3.4 Hz), 6.98 d (2Harom, J 7.8 Hz), 7.16–
7.52 m (7Harom), 7.71 d (2Harom, J 7.8 Hz), 7.85 d (2Harom
,
J 7.8 Hz), 8.36 s (1H, H5), 8.46 s (1H, NH). Found, %:
C 66.17; H 5.07; N 13.13. C24H21ClN4O2. Calculated,
%: C 66.59; H 4.89; N 12.94.
REFERENCES
1. Bratenko, M.K., Panimarchuk, O.I., Chornous, V.A., and
Vovk, M.V., Zh. Org. Khim., .2005, vol. 41, p. 99.
2. Diehl, V., Cuny, E., and Lichtantalen, F.W., Heterocycles,
1998, vol. 48, p. 1193.
3. Bratenko, M.K., Chornous, V.A., and Vovk, M.V., Zh. Org.
Khim., 2002, vol. 38, p. 432.
4. Gibson, H.S. and Bradshaw, R.W., Angew. Chem. Int. Ed.,
1968, vol. 7, p. 919.
5. Bratenko, M.K., Chornous, V.A., and Vovk, M.V., Zh. Org.
Khim., 2002, vol. 38, p. 622.
6. Gorbatenko, V.I., Zhuravlev, E.Z., and Samarai, L.I., Izotsia-
naty. Metody sinteza i fiziko-khimicheskie svoistva alkil-,
aril- i geterilizotsianatov (Isocyanates. Methods of Syn-
thesis and Physicochemical Properties of Alkyl, Aryl, and
Heteryl Isothiocyanates), Kiev: Naukova Dumka, 1987, 445 p.
7. Suvorov, N.N., Velezheva, V.S., and Yarosh, A.V., Khim.
Geterotsikl. Soed., 1975, p. 1099.
8. Curtius,T. and Sandhaas, W., J. pr. Chem., 1930, vol. 125, p. 90.
9. Buzilova, S.R., Shul’gina, V.M., and Gareev, G.A., Zh. Org.
Khim., 1984, vol. 20, p. 1795.
10. Siefken, W., Lieb. Ann., 1949, vol. 562, p. 75.
11. Cotarca, L., Delogu, P., Nardelli,A., and Sunjic, V., Synthesis,
1996, p. 553.
12. Drobnica, L., Kristian, P., andAugustin, P., The Chemistry
of Cyanates and Their Thioderivatives, Patai, S., Ed., New
York: Wiley Inc., 1977, part 2, p. 1003.
N-[3-(5-Chlorothienyl-2)-1-phenyl-4-pyrazolyl-
methyl]-N'-(4-chlorophenyl)urea (VIIb). Yield 63%,
1
mp 243–245°C. H NMR spectrum (DMSO-d6), d, ppm:
4.41 d (2H, CH2, J 3.5 Hz), 6.51 t (1H, NH, J 3.5 Hz),
7.08–7.52 m (8Harom), 7.82 d (2Harom, J 7.7 Hz), 8.42 s
(1H, H5), 8.52 s (1H, NH). Found, %: C 56.47; H 3.57;
N 12.93. C21H16Cl2N4OS. Calculated, %: C 56.89;
H 3.64; N 12.64.
3-Aryl(heteryl)-4-isothiocyanatopyrazoles VIIIa–
VIIIc. To a mixture of 4 mmol of amine IIIa, IIIf, or
IIIg and 0.41g (4 mmol) of triethylamine in 10 ml of
chloroform was added dropwise 0.31g (4 mmol) of carbon
disulfide maintaining the reaction temperature below
35°C. Then in succession was added dropwise 0.41g
(4 mmol) of triethylamine and 0.32 g (4 mmol) of acetyl
chloride maintaining the same temperature. The reaction
mixture was stirred for 4 h and poured into 50 ml of water,
the organic layer was separated, dried with K2CO3, the
solvent was evaporated, to the oily residue 15 ml of hexane
was added, and it was kept in a refrigerator for 5–7 days.
The solidified substance was recrystallized from a mixture
benzene–hexane, 3:1.
4-Isothiocyanatomethyl-1,3-diphenylpyrazole
13. Sovremennye metody organicheskogo sinteza (Modern
Methods of Oragnic Synthesis), Ioffe, B.V., Ed., Leningrad:
Khimiya, 1980, p. 166.
(VIIIa). Yield 50%, mp 95–97°C. IR spectrum (CH2Cl2),
–1
1
cm : 2060 (NCS). H NMR spectrum (CDCl3), d, ppm:
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 2 2005