Five-membered 2,3-dioxo heterocycles: LXXXII. Recyclization of dimethyl 4,5-dioxo-4,5-dihydro-1h-pyrrole-2,3-dicarboxylates in reaction with monosubstituted hydrazines. Crystalline and molecular structure of dimethyl 1-benzyl-5-(4-methylphenylcarbamoyl)-1

Article abstract of DOI:10.1134/S1070428012010174

Dimethyl 1-aryl(benzyl)-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates reacted with phenylhydrazine and benzylhydrazine to give dimethyl 1-aryl(benzyl)-5-[(aryl or benzyl)carbamoyl]-1H-pyrazole-3,4-dicarboxylates. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012010174

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 1, pp. 109–112. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © P.S. Silaichev, M.A. Chudinova, P.A. Slepukhin, A.N. Maslivets, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48,
No. 1, pp. 114–117.
Five-Membered 2,3-Dioxo Heterocycles: LXXXII.* Recyclization
of Dimethyl 4,5-Dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates
in Reaction with Monosubstituted Hydrazines. Crystalline
and Molecular Structure of Dimethyl 1-Benzyl-5-(4-methyl-
phenylcarbamoyl)-1H-pyrazole-3,4-dicarboxylate
P. S. Silaicheva, M. A. Chudinovab, P. A. Slepukhinc, and A. N. Maslivetsa,b
a Institute of Natural Sciences, Perm State University, ul. Genkelya 4, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Perm State University, ul. Bukireva 15, Perm, 614990 Russia
c Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
Received April 19, 2010
Abstract—Dimethyl 1-aryl(benzyl)-4,5-dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates reacted with phenyl-
hydrazine and benzylhydrazine to give dimethyl 1-aryl(benzyl)-5-[(aryl or benzyl)carbamoyl]-1H-pyrazole-3,4-
dicarboxylates.
DOI: 10.1134/S1070428012010174
Methyl 1-aryl-3-aroyl-4,5-dioxo-4,5-dihydro-1H-
pyrrole-2-carboxylates and 4,5-diaroyl-1-aryl-2,3-di-
hydro-1H-pyrrole-2,3-diones were reported to react
with substituted hydrazines to give substituted methyl
1,5-diaryl-4-(N-aryloxamoyl)-1H-pyrazole-3-carbox-
ylates [2, 3] and 3-aroyl-5-aryl-4-(N-aryloxamoyl)-1H-
pyrazoles [4, 5], respectively. In both cases, the proc-
ess involves successive nucleophilic attacks by the
primary and secondary amino groups of substituted
hydrazine at the carbon atom in position 2 (5) and
carbonyl carbon atom in the aroyl substituent on C3
(C4), followed by opening of the pyrrole ring at the
N1–C2(C5) bond. Reactions of 4,5-bis(alkoxycar-
bonyl)-substituted 1H-pyrrole-2,3-diones with hydra-
zine derivatives were not studied.
zyl)-1H-pyrazole-3,4-dicarboxylates IIIa–IIIg in good
yield (Scheme 1). The product structure was confirmed
by X-ray analysis of a single crystal of compound IIIf.
Compounds IIIa–IIIg were isolated as colorless or
light yellow crystalline substances which are poorly
soluble in common organic solvents and insoluble in
water and saturated hydrocarbons. The solubility of
N-phenyl derivatives IIIa–IIIe is appreciably lower
than that of their N-benzyl analogs IIIf and IIIg.
The IR spectra of IIIa–IIIg contained absorption
bands due to stretching vibrations of NH (3248–
3380 cm–1), “free” ester carbonyl group (1736–
1752 cm–1) and that involved in intramolecular hydro-
gen bond (1698–1712 cm–1), and amide carbonyl
group (1661–1680 cm–1); amide II band was observed
at 1557–1568 cm–1. Compounds IIIa–IIIg displayed in
We found that dimethyl 1-aryl- and 1-benzyl-4,5-
dioxo-4,5-dihydro-1H-pyrrole-2,3-dicarboxylates Ia–
Ie react with an equimolar amount of phenylhydrazine
(IIa) or benzylhydrazine (IIb) on heating in a boiling
2:1 mixture of anhydrous benzene and 1,4-dioxane
(reaction time 20–30 min; TLC monitoring) to give
dimethyl 5-[(aryl or benzyl)carbamoyl]-1-phenyl(ben-
1
the H NMR spectra signals from protons in the aro-
matic rings and substituents therein, two singlets from
ester methoxy groups (δ 3.70–3.91 ppm), and NH
singlet at δ 10.73–11.03 ppm. Methylene protons in the
benzyl substituent of compounds IIIf and IIIg resonat-
ed as a singlet at δ 5.48–5.49 ppm. In the 13C NMR
spectrum of IIIc, signals from the ester carbonyl
carbon atoms appeared at δC 156.30 and 161.79 ppm,
* For communication LXXXI, see [1].
109

SILAICHEV et al.
110
Scheme 1.
O
N
O
COOMe
HO
COOMe
OH
MeO
O
Δ
H
N
+
COOMe
NHR2
CONHR1
R2
NH2
O
COOMe
O
N
N
HN
NH
R2
MeO
R1
R1
Ia–Ie
IIa, IIb
IVa–IVc
MeOCO
COOMe
N
–H2O
CONHR1
N
R2
IIIa–IIIg
I, R1 = Ph (a), PhCH2 (b), 4-MeC6H4 (c), 4-MeOC6H4 (d), 4-ClC6H4 (e); II, R2 = Ph (a), PhCH2 (b); III, R2 = Ph, R1 = Ph (a),
PhCH2 (b), 4-MeC6H4 (c), 4-MeOC6H4 (d), 4-ClC6H4 (e); R2 = PhCH2, R1 = 4-MeC6H4 (f), 4-MeOC6H4 (g); IV, R2 = Ph, R1 =
PhCH2 (a), 4-MeC6H4 (b), 4-MeOC6H4 (c).
and the amide carbonyl carbon atom gave a signal at
ciable contribution of specific contacts (π–π interac-
δC 160.92 ppm.
tions, intermolecular hydrogen bonds, etc.).
The structure of compound IIIf was unambiguously
determined by X-ray analysis (see figure). Compound
crystallized in triclinic crystal system (centrosym-
metric space group). The bond lengths in molecule IIIf
conform to the corresponding standard values. The
molecular conformation is determined by intramolec-
ular hydrogen bond N3H · · · O1 with a distance of
2.731(2) Å. Polar methoxycarbonyl and amide groups
are turned with respect to the pyrazole ring plane;
the corresponding dihedral angles are as follows:
C4C5C6N3 25.3(2), O1C7C4C5 –30.4(2), C4C3C1O3
–35.9(2)°. Packing of molecules IIIf in crystal is
governed by van der Waals interactions without appre-
Presumably, compounds IIIa–IIIg are formed via
initial addition of the primary amino group in mono-
substituted hydrazine at the C2 atom of dioxopyrrole
Ia–Ie with formation of intermediate IV which under-
goes cleavage of the pyrrole ring at the N1–C2 bond.
The subsequent intramolecular nucleophilic attack by
the secondary amino group in the hydrazine fragment
on the carbonyl carbon atom neighboring to the
carbamoyl fragment and elimination of water molecule
yields final pyrazole structure III (Scheme 1).
We made an attempt to isolate intermediate prod-
ucts in the above reaction with a view to confirm the
proposed mechanism. By reacting compounds Ib–Id
with phenylhydrazine (IIa) in benzene at room tem-
perature (reaction time 1–2 min) we succeeded in
isolating the primary addition products, dimethyl
1-aryl(benzyl)-4-hydroxy-5-oxo-2-(2-phenylhydrazino)-
2,5-dihydro-1H-pyrrole-2,3-dicarboxylates IVa–IVc.
C14 C13
C18
C22
C17
C12
C19
C16
O5
C6
C11
C10
C9
C20
C5
N1
C3
Compounds IVa–IVc are colorless crystalline sub-
stances which melt with decomposition. They are
readily soluble in DMSO and DMF, poorly soluble in
other common organic solvents, and insoluble in
alkanes and water. Compounds IVa–IVc showed posi-
tive color test (cherry color) for enol hydroxy group
upon treatment with an alcoholic solution of iron(III)
chloride.
C21
N3
N2
C4
C7
O2
O1
O4
C1
O3
C8
C2
Structure of the molecule of dimethyl 1-benzyl-5-(4-methyl-
phenylcarbamoyl)-1H-pyrazole-3,4-dicarboxylate (IIIf)
according to the X-ray diffraction data; non-hydrogen atoms
are shown as thermal vibration ellipsoids with a probability
of 50%.
The IR spectra of IVa–IVc contained absorption
bands typical of stretching vibrations of NH and enol
OH groups (broadened band at 3243–3324 cm–1), ester
carbonyl groups (1712–1752 cm–1), and lactam car-
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FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: LXXXII.
111
bonyl group (1680–1703 cm–1). In the 1H NMR spectra
of IVa–IVc we observed signals from protons in the
aromatic rings and substituents therein, two singlets at
δ 3.00–3.78 ppm from the ester methoxy groups, two
singlets at δ 5.93–6.48 ppm from the NH protons, and
a broadened singlet in the region δ 9.03–11.94 ppm
due to enol hydroxy proton.
3.58 s and 3.69 s (3H each, OMe), 6.24 s (2H, CH2),
7.12–7.41 m (10H, C6H5), 10.91 t (1H, NH). Found,
%: C 64.16; H 4.86; N 10.61. C21H19N3O5. Calculated,
%: C 64.12; H 4.87; N 10.68.
Dimethyl 5-(4-methylphenylcarbamoyl)-1-phen-
yl-1H-pyrazole-3,4-dicarboxylate (IIIc). Yield 84%,
mp 219–220°C (from ethanol). IR spectrum, ν, cm–1:
3314 (NH), 1736 (3-C=O), 1712 (4-C=O), 1676 (C=O,
Heating of compounds IVa–IVc in a boiling 2:1
mixture of anhydrous benzene and 1,4-dioxane over
a period of 20–30 min (i.e., under the conditions corre-
sponding to the synthesis of compounds III), resulted
in their recyclization with formation of compounds
IIIa, IIIc, and IIId in good yield. The products were
identical to those obtained directly from pyrrolediones
I and monosubstituted hydrazines.
1
amide), 1557 (δNH). H NMR spectrum, δ, ppm:
2.26 s (3H, Me), 3.75 s and 3.91 s (3H each, OMe),
7.15 d (2H, J = 8.2 Hz), 7.41 d (2H, J = 8.3 Hz), 7.50–
7.61 m (5H, Ph), 10.94 s (1H, NH). 13C NMR spec-
trum, δC, ppm: 52.15 (OMe), 52.64 (OMe), 119.71–
141.17 (Carom, C4, C5), 143.41 (C3), 156.30 (C=O),
160.92 (CONH), 161.79 (C=O). Found, %: C 64.17;
H 4.86; N 10.59. C21H19N3O5. Calculated, %: C 64.12;
H 4.87; N 10.68.
The described reaction is an example of recycliza-
tion of pyrrolediones by the action of hydrazines,
which follows previously unknown scheme.
Dimethyl 5-(4-methoxyphenylcarbamoyl)-1-
phenyl-1H-pyrazole-3,4-dicarboxylate (IIId). Yield
81%, mp 158–159°C (from ethanol). IR spectrum, ν,
cm–1: 3281 (NH), 1752 (3-C=O), 1698 (4-C=O), 1668
EXPERIMENTAL
1
The IR spectra were recorded on an FSM-1201
spectrometer from samples dispersed in mineral oil.
(C=O, amide), 1568 (δNH). H NMR spectrum, δ,
ppm: 3.73 s (3H, C6H4OMe), 3.76 s and 3.91 s (3H
each, OMe), 6.91 d (2H, J = 8.6 Hz), 7.43 d (2H, J =
8.6 Hz), 7.50–7.62 m (5H, Ph), 10.87 s (1H, NH).
Found, %: C 61.68; H 4.75; N 10.24. C21H19N3O6. Cal-
culated, %: C 61.61; H 4.68; N 10.26.
1
The H and 13C NMR spectra were measured on
a Bruker AM-400 spectrometer at 400 and 100 MHz,
respectively, using DMSO-d6 as solvent, and tetra-
methylsilane as internal reference. The purity of the
isolated compounds was checked by TLC on Silufol
plates using benzene–ethyl acetate (5:1) as eluent.
Dimethyl 5-(4-chlorophenylcarbamoyl)-1-phen-
yl-1H-pyrazole-3,4-dicarboxylate (IIIe). Yield 78%,
mp 208–210°C (from ethanol). IR spectrum, ν, cm–1:
3300 (NH), 1746 (3-C=O), 1703 (4-C=O), 1661 (C=O,
Dimethyl 1-phenyl-5-phenylcarbamoyl-1H-pyr-
azole-3,4-dicarboxylate (IIIa). A solution of 1 mmol
of phenylhydrazine in 10 ml of anhydrous 1,4-dioxane
was added to a solution of 1 mmol of compound Ia in
20 ml of anhydrous benzene. The mixture was heated
for 25 min under reflux and evaporated, and the
residue was recrystallized from ethanol. Yield 82%,
mp 181–183°C (from ethanol). IR spectrum, ν, cm–1:
3298 (NH), 1746 (3-C=O), 1703 (4-C=O), 1661 (C=O,
1
amide), 1563 (δNH). H NMR spectrum, δ, ppm:
3.75 s and 3.91 s (3H each, OMe), 7.42 d (2H, J =
9.1 Hz), 7.45–7.61 m (5H, Ph), 7.56 d (2H, J =
9.1 Hz), 11.19 s (1H, NH). Found, %: C 59.01; H 4.22;
Cl 8.26; N 9.84. C21H18ClN3O5. Calculated, %:
C 58.95; H 4.24; Cl 8.29; N 9.82.
Dimethyl 1-benzyl-5-(4-methylphenylcarba-
moyl)-1H-pyrazole-3,4-dicarboxylate (IIIf). Yield
73%, mp 208–210°C (from ethanol). IR spectrum, ν,
cm–1: 3344 (NH), 1751 (3-C=O), 1700 (4-C=O), 1662
1
amide), 1563 (δNH). H NMR spectrum, δ, ppm:
3.75 s and 3.91 s (3H each, OMe), 7.13–7.62 m
(10H, C6H5), 11.03 s (1H, NH). Found, %: C 63.37;
H 4.42; N 10.99. C20H17N3O5. Calculated, %: C 63.32;
H 4.52; N 11.08.
1
(C=O, amide), 1562 (δNH). H NMR spectrum, δ,
ppm: 2.28 s (3H, Me), 3.70 s and 3.85 s (3H each,
OMe), 5.49 s (2H, CH2), 7.18 d (2H, J = 8.8 Hz),
7.27–7.36 m (5H, Ph), 7.51 d (2H, J = 8.8 Hz), 10.80 s
(1H, NH). Found, %: C 64.82; H 5.26; N 10.26.
C22H21N3O5. Calculated, %: C 64.86; H 5.20; N 10.31.
Compounds IIIb–IIIg were synthesized in a similar
way.
Dimethyl 5-benzylcarbamoyl-1-phenyl-1H-pyra-
zole-3,4-dicarboxylate (IIIb). Yield 79%, mp 147–
149°C (from ethanol). IR spectrum, ν, cm–1: 3314
(NH), 1736 (3-C=O), 1712 (4-C=O), 1676 (C=O,
X-Ray diffraction data for compound IIIf.
X-Ray analysis was performed on an Xcalibur-3 dif-
fractometer with a CCD detector [λ(MoKα) 0.71073 Å,
1
amide), 1563 (δNH). H NMR spectrum, δ, ppm:
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SILAICHEV et al.
112
graphite monochromator, ω-scanning through a step of
1°, temperature 295(2) K]. The structure was solved by
the direct method and was refined with the aid of
SHELXTL-97 software package [6]. No correction for
absorption was introduced. The positions and tempera-
ture parameters of non-hydrogen atoms were refined
first in isotropic and then in anisotropic approximation
by the full-matrix least-squares procedure. Hydrogen
atoms were localized by the electron density maxima,
and their positions were refined according to the riding
model. Triclinic crystal system, space group P-1; unit
cell parameters: a = 7.9450(7), b = 11.2170(13), c =
11.7450(10) Å; α = 85.548(8), β = 84.326(7), γ =
76.264(9)°; V = 1010.20(17) Å3; Z = 2; C22H21N3O5;
μ = 0.096 mm–1. Total of 5950 reflections were meas-
ured in the range 2.63 < θ < 28.28°, 4848 reflections
were independent (Rint 0.0168), and 2291 reflections
were characterized by I > 2σ(I); completeness 98.4%
for θ = 26.00°. The final divergence factors were R1 =
0.0384, wR2 = 0.0850 [reflections with I > 2σ(I)] and
R1 = 0.0922, wR2 = 0.0905 (all reflections); goodness
of fit S = 1.006; maximal and minimal residual elec-
tron density peaks 0.211 and –0.163 ē/Å3. The com-
plete set of crystallographic data for compound IIIf
was deposited to the Cambridge Crystallographic Data
Centre (entry no. CCDC 855435) and is available at
www.ccdc.cam.ac.uk/data_request/cif upon request.
(3H each, OMe), 4.29 d and 4.88 d (1H each, CH2, J =
15.9 Hz), 5.93 s (1H, NH), 6.48 s (1H, NH), 6.57–
7.33 m (10H, Ph), 11.94 br.s (1H, OH). Found, %:
C 61.34; H 5.12; N 10.23. C21H21N3O6. Calculated, %:
C 61.31; H 5.14; N 10.21.
Compounds IVb and IVc were synthesized in
a similar way.
Dimethyl 4-hydroxy-1-(4-methylphenyl)-5-oxo-
2-(2-phenylhydrazino)-2,5-dihydro-1H-pyrrole-2,3-
dicarboxylate (IVb). Yield 74%, mp 114–116°C
(from benzene–hexane). IR spectrum, ν, cm–1: 3319,
3291, 3243 (OH, NH); 1752, 1707 (C=O, ester); 1680
1
(C5=O). H NMR spectrum, δ, ppm: 2.26 s (3H, Me),
3.63 s and 3.66 s (3H each, OMe), 5.39 s (1H, NH),
5.97 s (1H, NH), 6.57–7.33 m (9H, Harom), 11.99 br.s
(1H, OH). Found, %: C 61.34; H 5.12; N 10.23.
C21H21N3O6. Calculated, %: C 61.31; H 5.14; N 10.21.
Dimethyl 4-hydroxy-1-(4-methoxyphenyl)-5-oxo-
2-(2-phenylhydrazino)-2,5-dihydro-1H-pyrrole-2,3-
dicarboxylate (IVc). Yield 76%, mp 83–84°C (from
benzene–hexane). IR spectrum, ν, cm–1: 3301, 3298,
3246 (OH, NH); 1749 (2-C=O); 1713 (3-C=O); 1701
1
(C5=O). H NMR spectrum, δ, ppm: 3.61 s (3H,
C6H4OMe), 3.66 s and 3.78 s (3H each, OMe), 5.33 s
(1H, NH), 6.57–7.17 m (10H, Harom, NH), 9.03 br.s (1H,
OH). Found, %: C 58.96; H 4.91; N 9.84. C21H21N3O7.
Calculated, %: C 59.01; H 4.95; N 9.83.
Dimethyl 1-benzyl-5-(4-methoxyphenylcarba-
moyl)-1H-pyrazole-3,4-dicarboxylate (IIIg). Yield
71%, mp 140–141°C (from ethanol). IR spectrum, ν,
cm–1: 3346 (NH), 1749 (3-C=O), 1709 (4-C=O), 1676
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (project no. 2.19.10).
1
(C=O, amide), 1568 (δNH). H NMR spectrum, δ,
ppm: 3.71 s (3H, C6H4OMe), 3.75 s and 3.84 s (3H
each, OMe), 5.48 s (2H, CH2), 6.95 d (2H, J = 9.2 Hz),
7.26–7.36 m (5H, Ph), 7.52 d (2H, J = 9.2 Hz), 10.73 s
(1H, NH). Found, %: C 62.37; H 5.54; N 9.87.
C22H21N3O6. Calculated, %: C 62.41; H 5.60; N 9.92.
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in 10 ml of anhydrous benzene was added dropwise to
a solution of 1 mmol of compound Ib in 20 ml of
anhydrous benzene. The mixture was kept for 1 min at
room temperature, the solvent was removed, and the
product was purified by reprecipitation from benzene
with hexane. Yield 72%, mp 127–128°C (from ben-
zene–hexane). IR spectrum, ν, cm–1: 3324, 3301, 3245
(OH, NH); 1752 (2-C=O); 1717 (3-C=O); 1703
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(C5=O). H NMR spectrum, δ, ppm: 3.00 s and 3.60 s
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012