Synthesis of 3,5-disubstituted pyrazole derivatives with a carbamate function

Article abstract of DOI:10.1134/S1070428009080156

One-pot reaction of 1,3-dipolar cycloaddition of aryldiazamethanes generated in situ from the sodium salts of tosylhydrazones of benzaldehyde, p-nitro-, p-methoxy-, and 3,4-dimethoxybenzaldehyde to propargyl-N-phenyl carbamate under heating led to the for

Full text of DOI:10.1134/S1070428009080156

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 8, pp. 1208−1209. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © A.V. Velikorodov, V.B. Kovalev, O.O. Krivosheev, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 8,
pp. 1217−1218.
Synthesis of 3,5-Disubstituted Pyrazole Derivatives
with a Carbamate Function
A. V. Velikorodov, V. B. Kovalev, and O. O. Krivosheev
Astrakhan State University, Astrakhan, 414056 Russia
e-mail: avelikorodov@mail.ru
Received October 8, 2008
Abstract—One-pot reaction of 1,3-dipolar cycloaddition of aryldiazamethanes generated in situ from the sodium
salts of tosylhydrazones of benzaldehyde, p-nitro-, p-methoxy-, and 3,4-dimethoxybenzaldehyde to propargyl-N-
phenyl carbamate under heating led to the formation of 3,5-disubstituted pyrazoles in good yield and high
regioselectivity.
DOI: 10.1134/S1070428009080156
Pyrazole derivatives attract great interest for these
compounds are widely used as drugs, dyes, anesthetics,
and agricultural chemicals [1, 2]. They are endowed
with bacteriostatic, bactericidal, insecticide, fungicide,
sedative, antitumor, and psycho-pharmacological action.
Pyrazoles are also used as antioxidant additives to fuels
[3].
of toxic and potentially explosive diazo compounds.
However the synthetic opportunities and the application
limits of this method of pyrazoles synthesis were poorly
understood.
We investigated the 1,3-dipolar cycloaddition to
propargyl-N-phenyl carbamate of aryldiazomethanes
generated in the course of the reaction from sodium salts
of tosylhydrazones obtained from appropriate aromatic
aldehydes .
The most important preparation methods of this class
heterocycles are hydrazines reaction with β-difunctional
compounds [4] and 1,3-dipolar cycloaddition of diazo
compounds to a triple bond 5].
The cycloaddition of aryldiazomethanes obtained from
the sodium salts of tosylhydrazones of benzaldehyde,
4-methoxy-, 3,4-dimethoxy-, and 4-nitrobenzaldehyde
occurred regioselectively to the terminal triple bond of
dipolarophile II affording 3,5-disubstituted pyrazoles IIIa–
IIId in 22–70% yield (see the scheme).
Recently a convenient one-pot method of pyrazoles
preparation was developed consisting in the 1,3-dipolar
cycloaddition of aryldiazomethanes generated from stable
sodium salts of tosylhydrazones in situ [6]. An obvious
advantage of this method is avoiding the stage of isolation
Scheme.
(1) TsNHNH2
MeCN, 20°C, 3 h
,
Na+
O
N_
_
+
D
CH N N
Ar
Ar
N
Ts
2.5 N NaOH
Ar
H
B
Ia_Id
A
PhNHCO2CH2C CH
N
NH
II
C
50oC, 48 h
Ar
CH2O2CHNPh
IIIa_IIId
Ar = Ph (a), 4-MeOC6H4 (b), 3,4-(MeO)2C6H3 (c), 4-NO2C6H4 (d).
1208

SYNTHESIS OF 3,5-DISUBSTITUTED PYRAZOLE DERIVATIVES
1209
The structure of 3-aryl-5-phenylaminocarbonyl-
[3-(4-Methoxyphenyl)-1H-pyrazol-5-yl]methyl
N-phenylcarbamate (IIIb). Yield 1.3 g (54%), colorless
crystals, mp 138–140°C. IR spectrum, ν, cm–1: 3360
(NH), 1720 (C=O), 1600, 1520, 1500 (C–Carom). 1H NMR
spectrum, δ, ppm: 4.15 s (3H, OCH3), 5.35 s (2H, OCH2),
6.50 s (1H, H4), 6.91 d (2Harom, J 8.5 Hz), 7.36–7.02 m
(5Harom), 7.76 d (2Harom, J 8.5 Hz), 9.56 s (1H, NH),
9.79 s (1H, NH). Found, %: C 66.64; H 4.96; N 13.07.
C18H17N3O3. Calculated, %: C 66.87; H 5.26; N 13.00.
oxymethyl-1H-pyrazoles IIIa–IIId was confirmed by IR
1
and H NMR spectra.
1
In the H NMR spectra of pyrazoles IIIa–IIId the
signal of proton H4 appeared in the region 6.48–6.53 ppm
in agreement with the published data [7, 8].
The highest yield was obtained from benzaldehyde
(Ia). The preparation of pyrazoles IIIb–IIId was
attended with the formation of intractable tar considerably
reducing the yield of the target products.
[3-(3,4-Dimethoxyphenyl)-1H-pyrazol-5-yl]-
methyl N-phenylcarbamate (IIIc). Yield 1.3 g (51%),
colorless crystals, mp 79–81°C. IR spectrum, ν, cm–1:
3365 (NH), 1720 (C=O), 1610, 1525, 1500 (C–Carom).
1H NMR spectrum, δ, ppm: 3.81 s (3H, OCH3), 3.92 s
(3H, OCH3), 5.37 s (2H, OCH2), 6.48 s (1H, H4), 6.95 d
The high stereoselectivity of the cycloaddition of
aryldiazomethanes is controlled by HUMO of the diazo
compound when react the terminal atoms with a large
orbital factor [9].
(1Harom, J 8.5 Hz), 7.36–7.02 m (6Harom), 7.86 d (1Harom
,
EXPERIMENTAL
J 8.5 Hz), 9.54 s (1H, NH), 9.79 s (1H, NH). Found, %:
C 64.63; H 5.12; N 12.05. C19H19N3O4. Calculated, %:
C 64.59; H 5.38; N 11.90.
1H NMR spectra were registered on a spectrometer
Bruker DRX 500 (500.13 ΜHz) in DMSO-d6, internal
reference TMS. IR spectra were recorded on a spec-
trophotometer Specord M82 from pellets with KBr. The
purity of compounds obtained was checked by TLC on
Silufol UV-254 plates. Tosylhydrazine was obtained by
procedure [10], mp 104–107°C.
[3-(4-Nitrophenyl)-1H-pyrazol-5-yl]methyl N-
phenylcarbamate (IIId). Yield 0.55 g (22%), light
yellow crystals, mp 159–160°C. IR spectrum, ν, cm–1:
3360 (NH), 1725 (C=O), 1605, 1520, 1500 (C–Carom).
1H NMR spectrum, δ, ppm: 5.37 s (2H, OCH2), 6.53 s
(1H, H4), 7.37–7.02 m (5Harom), 7.81 d (2Harom, J 8.6
Hz), 8.38 d (2Harom, J 8.6 Hz), 9.55 s (1H, NH), 9.79 s
(1H, NH). Found, %: C 60.23; H 3.97; N 16.61.
C17H14N4O4. Calculated, %: C 60.36; H 4.14; N 16.57.
3-Aryl-5-phenylaminocarbonyloxymethyl-1H-
pyrazoles IIIa–IIId. To a solution of 0.28 g (1.5 mmol)
of tosylhydrazine in 15 ml of acetonitrile was added
1.5 mmol of aldehyde Ia–Id, the mixture was stirred for
3 h at room temperature, 1.5 mmol of 5 N solution of
sodium hydroxide was added, and the stirring at the same
temperature continued for 20 min more. To the obtained
sodium salt of tosylhydrazone was added 1.3 g (7.5 mmol)
of propargyl-N-phenyl carbamate (II), the mixture was
stirred at 50°C for 48 h. The volatile substances were
removed in a vacuum, the residue was dissolved in 70 ml
of a mixture water–ethyl acetate, 1 : 1. The organic layer
was separated, dried with magnesium sulfate, the solvent
was removed, the residue was subjected to column
chromatography on neutral aluminum oxide, eluent ethyl
acetate.
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mp 94–95°C. IR spectrum, ν, cm–1: 3400 (NH), 1720
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δ, ppm: 5.35 s (2H, OCH2), 6.51 s (1H, H4), 7.37–
7.02 m (10Harom), 9.54 s (1H, NH), 9.79 s (1H, NH).
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