Five-membered 2,3-dioxo heterocycles: LXXIV. Recyclization of 3-aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzohydrazides. Crystalline and molecular structure of N-[2,4-dihydroxy-5-oxo- 3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-yl] benzamide

Article abstract of DOI:10.1134/S107042801103016X

Recyclization of 3-aroyl-1H-pyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzoic acid hydrazides gave N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4- dihydroquinoxalin-2-yl)-2-aryl-2,5-dihydro-1H-pyrrol-1-yl]benzamides whose structure was proved by X-ray analysis.

Full text of DOI:10.1134/S107042801103016X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 3, pp. 417–420. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © I.V. Mashevskaya, I.G. Mokrushin, L.V. Kuslina, Z.G. Aliev, A.N. Maslivets, 2011, published in Zhurnal Organicheskoi Khimii, 2011,
Vol. 47, No. 3, pp. 424–427.
Five-Membered 2,3-Dioxo Heterocycles:
LXXIV.* Recyclization of 3-Aroylpyrrolo[1,2-a]quinoxaline-
1,2,4(5H)-triones by the Action of Benzohydrazides. Crystalline
and Molecular Structure of N-[2,4-Dihydroxy-5-oxo-
3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-phenyl-
2,5-dihydro-1H-pyrrol-1-yl]benzamide
I. V. Mashevskayaa,b, I. G. Mokrushinb, L. V. Kuslinab, Z. G. Alievc, and A. N. Maslivetsa,b
a Institute of Natural Sciences, Perm State University, Perm, Russia
b Perm State University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
c Institute of Chemical Physics Problems, Russian Academy of Sciences,
Chernogolovka, Moscow oblast, Russia
Received April 6, 2010
Abstract—Recyclization of 3-aroyl-1H-pyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones by the action of benzoic
acid hydrazides gave N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-aryl-2,5-dihydro-1H-
pyrrol-1-yl]benzamides whose structure was proved by X-ray analysis.
DOI: 10.1134/S107042801103016X
Recyclizations and heterocyclizations of 1H-pyr-
role-2,3-diones fused at the [a] side to various hetero-
cycles by the action of difunctional nucleophiles
provide convenient methods for the synthesis of het-
erocyclic systems [2]. We previously showed that
fusion of a dioxopyrrole ring to quinoxaline fragment
gives rise to a specific polycarbonyl heterocyclic
system (pyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones)
which in most cases remains unchanged in reactions
with nucleophiles; therefore, it can be used to append
new heterocycles [2–4]. On the other hand, while
studying reaction of 3-aroylpyrrolo[1,2-a]quinoxaline-
1,2,4(5H)-triones with benzylamine we were the first
to observed recyclization of the pyrrole ring with
formation of 3-(2-aryl-1-benzyl-2,4-dihydroxy-5-oxo-
pyrrolidin-3-yl)quinoxalin-2(1H)-ones [5]. With
a view to elucidate how nucleophile nature affects
the direction of nucleophilic heterocyclization or recy-
clization of 3-aroylpyrrolo[1,2-a]quinoxaline-
1,2,4(5H)-triones we examined their reactions with
benzoic acid hydrazides [6].
3-Aroylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones
Ia–Id reacted with equimolar amounts of benzohy-
drazides IIa–IIc in boiling anhydrous acetonitrile to
produce in 1–3 min (until the dark violet color typical
of initial pyrroloquinoxalinetriones disappeared) the
corresponding N-[2,4-dihydroxy-5-oxo-3-(3-oxo-3,4-
dihydroquinoxalin-2-yl)-2-aryl-2,5-dihydro-1H-pyrrol-
1-yl]benzamides IIIa–IIIg (Scheme 1) whose structure
was proved by X-ray analysis of a single crystal of
compound IIIa.
Compounds IIIa–IIIg were isolated as light yellow
high-melting crystalline substances which melted with
decomposition. The products were readily soluble in
dimethylformamide and dimethyl sulfoxide, poorly
soluble in other common organic solvents, and
insoluble in water and saturated hydrocarbons. They
showed a positive color test (cherry color) for enolic
hydroxy group on treatment with an alcoholic solution
of iron(III) chloride.
The IR spectra of IIIa–IIIg contained absorption
bands belonging to stretching vibrations of N–H and
O–H bonds (3150–3390 cm–1), lactam carbonyl group
* For communication LXXIII, see [1].
417

MASHEVSKAYA et al.
418
Scheme 1.
H
N
H
N
O
O
O
O
O
R1
O
O
R2
Ar
N
H
O
R1
+
NHNH2
N
H
N
R2
Ar
O
N
H
O
Ia–Id
IIa–IIc
H
N
O
HO
R2
Ar
N
R1
N
NH
O
HO
O
IIIa–IIIg
I, Ar = Ph (a), 4-MeC6H4 (b), 4-ClC6H4 (c), 4-O2NC6H4 (d); II, R1 = R2 = H (a); R1 = OH, R2 = H (b); R1 = H, R2 = O2N (c);
III, Ar = Ph, R1 = R2 = H (a); Ar = Ph, R1 = OH, R2 = H (b), Ar = Ph, R1 = H, R2 = O2N (c); Ar = 4-MeC6H4, R1 = OH, R2 = H (d);
Ar = 4-ClC6H4, R1 = R2 = H (e); Ar = 4-ClC6H4, R1 = OH, R2 = H (f); Ar = 4-O2NC6H4, R1 = R2 = H (g).
in the pyrrole ring (1730–1760 cm–1), lactam carbonyl
group in the quinoxaline ring (1680–1703 cm–1) and
amide carbonyl group (1637–1660 cm–1). Compounds
to 8-H in the quinoxaline fragment was displaced
downfield (δ 7.81–8.15 ppm, d) due to deshielding
effect of the N1 atom.
1
IIIa–IIIg displayed in the H NMR spectra signals
Figure 1 shows the structure of molecule IIIa
according to the X-ray diffraction data. It is seen that
molecules IIIa in crystal are stabilized by the intra-
molecular hydrogen bond O3–H3 ···O1 with the dis-
tance O3 ···O1 equal to 2.504 Å. However, the quin-
oxaline ring system slightly deviates from coplanarity
with the pyrrole ring plane: the corresponding dihedral
angle is equal to 12.8°, which may be due to speci-
ficity of crystal packing. The benzene ring is oriented
bisectionally with respect to the pyrrole ring plane, so
that these rings are orthogonal. The benzoylamino
group is not planar, and its configuration is determined
by the following torsion angles: N4C19C20C21 134.8,
N3N4C19C20 166.5, C5N3N4C19 67.8°.
Compound IIIa crystallized as 1:1 solvate with di-
methylformamide. Molecules IIIa in crystal are linked
to centrosymmetric dimers (Fig. 2) through inter-
molecular hydrogen bonds N1–H1···O5 (2.828 Å) and
O2–H2···O1 (2.795 Å). In addition, N4–H4···O6 hydro-
gen bond (2.808 Å) links molecule IIIa to solvate
DMF molecule.
from aromatic protons and protons in substituents in
the aromatic ring, a singlet from the 2-OH group
(δ 6.46–7.05 ppm), a singlet from the amide NH
proton (δ 10.13–10.88 ppm), a singlet from the
phenolic OH group (δ 11.46–11.51 ppm; IIIb, IIId,
IIIf), a singlet from the quinoxaline NH proton
(δ 13.26–13.46 ppm), and a singlet from proton in the
enolic hydroxy group (4-OH, δ 14.32–14.70 ppm).
Among signals in the aromatic region, that belonging
O1
N1
O3
C4
C14
C1
C2
C13
C15
C16
C3
O4
C5
N3
N4
N2
C18
C17
C6
O2
C8
O5
C9
C10
C7
C12
C25
C24
C19
C20
C11
C23
C21
Presumably, compounds IIIa–IIIg are formed via
initial nucleophilic attack by the amino nitrogen atom
of hydrazide II on the carbonyl carbon atom in posi-
tion 1 of pyrroloquinoxaline I. Cleavage of the C1–N10
bond is followed by attack by the same nitrogen atom
on the aroyl carbonyl carbon atom with closure of new
pyrrole ring.
C22
Fig. 1. Structure of the molecule of N-[2,4-dihydroxy-5-oxo-
3-(3-oxo-3,4-dihydroquinoxalin-2-yl)-2-phenyl-2,5-dihydro-
1H-pyrrol-1-yl]benzamide (IIIa) according to the X-ray
diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 3 2011

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: LXXIV.
EXPERIMENTAL
419
The IR spectra were recorded on an FSM-120
spectrometer. The 1H and 13C NMR spectra were meas-
ured on a Bruker AM-400 spectrometer at 400 MHz
O5
C19
N1A
O1A
N4
N3
O4
C5
C4
O6
C26
N5
1
(for H) using DMSO-d6 as solvent and tetramethyl-
silane as internal standard. The purity of the isolated
compounds was checked by TLC on Silufol plates
using benzene–ethyl acetate (5:1) or ethyl acetate as
eluent; spots were visualized by treatment with iodine
vapor and by UV irradiation.
O2
O3
O3A
O1
N1
C6
C3
C2
O2A
C26A
N2
N5A
O6A
O4A
O5A
N4A
N-[2,4-Dihydroxy-5-oxo-3-(3-oxo-3,4-dihydro-
quinoxalin-2-yl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-
yl]benzamide (IIIa). A solution of 1.0 mmol of ben-
zoic acid hydrazide in 20 ml of anhydrous acetonitrile
was added to a solution of 1.0 mmol of compound Ia
in 30 ml of anhydrous acetonitrile, and the mixture was
heated for 2 min under reflux. The mixture was cooled,
and the precipitate was filtered off and recrystallized
from acetonitrile–DMF (10:1). Yield 59%, mp 229–
231°C. IR spectrum, ν, cm–1: 3370, 3150 (OH, NH);
1760 (C5=O); 1680 (C3′=O); 1650 (C=O, amide).
1H NMR spectrum, δ, ppm: 6.60 s (1H, 2-OH), 7.14–
7.95 m (14H, Harom), 10.50 s (1H, NH), 13.26 s (1H,
4′-H), 14.50 s (1H, 4-OH). Found, %: C 66.13; H 4.03;
N 12.38. C25H18N4O5. Calculated, %: C 66.08; H 3.99;
N 12.33.
Fig. 2. Packing of molecules IIIa in crystal.
for all 4085 reflections (360 refined parameters); good-
ness of fit 1.020. The maximal peak in the difference
synthesis of electron density was 0.652 e/Å3.
Compounds IIIb–IIIg were synthesized as de-
scribed above for IIIa.
N-[2,4-Dihydroxy-5-oxo-3-(3-oxo-3,4-dihydro-
quinoxalin-2-yl)-2-phenyl-2,5-dihydro-1H-pyrrol-1-
yl]-2-hydroxybenzamide (IIIb). Yield 68%, mp 212–
214°C (from MeCN). IR spectrum, ν, cm–1: 3390,
3150 (OH, NH); 1730 (C5=O); 1680 (C3′=O), 1660
(C=O, amide). 1H NMR spectrum, δ, ppm: 6.79 s (1H,
2-OH), 6.88–7.63 m (12H, Harom), 7.81 d (1H, 8′-H,
J = 7.9 Hz), 10.18 s (1H, NH), 11.51 s (1H, OH),
13.30 s (1H, 4′-H), 14.56 s (1H, 4-OH). Found, %:
C 63.80; H 3.82; N 11.90. C25H18N4O6. Calculated, %:
C 63.83; H 3.86; N 11.91.
X-Ray diffraction data for compound (IIIa).
Well defined tetrahedral yellow prisms, C25H18N4O5·
(CH3)2NCHO; M 527.53; triclinic crystal system,
space group P-1. Unit cell parameters: a = 10.644(1),
b = 11.286(2), c = 12.742(2) Å; α = 116.11(1), β =
101.82(3), γ = 92.35(1)°; V = 1286.6(3) Å3; dcalc
=
1.362 g/cm3; Z = 2. Experimental reflection intensities
were measured on a KM-4 (KUMA Diffraction)
automatic four-circle diffractometer with χ-geometry
[monochromatized MoKα irradiation, ω/2Θ-scanning
in the range 1.90–25.00° (90.1% of reciprocal space)].
Total of 4760 reflections were measured, 4085 of
which were independent (Rint = 0.0409). No correction
for absorption was introduced (μ = 0.095 mm–1). The
structure was solved by the direct method using SIR92
program [7] with subsequent calculation of electron
density maps. Hydrogen atoms were placed into posi-
tions calculated on the basis of geometry considera-
tions and were refined according to the riding model.
The positions of non-hydrogen atoms were refined by
the least-squares procedure in full-matrix anisotropic
approximation (SHELXL-97 [8]). The final divergence
factors were R1 = 0.0653, wR2 = 0.1512 for 2338 re-
flections with I ≥ 2σ(I) and R1 = 0.1308, wR2 = 0.1832
N-[2,4-Dihydroxy-5-oxo-3-(3-oxo-3,4-dihydro-
quinoxalin-2-yl)-2-phenyl-2,5-dihydro-1H-pyrrol-
1-yl]-3-nitrobenzamide (IIIc). Yield 68%, mp 145–
148°C (from MeCN–DMF, 10:1). IR spectrum, ν,
cm–1: 3390, 3164 (OH, NH); 1740 (C5=O); 1688
1
(C3″=O); 1640 (C=O, amide). H NMR spectrum, δ,
ppm: 6.75 s (1H, 2′-OH), 7.16–7.79 m (10H, Harom),
8.15 d (1H, 8″-H, J = 7.9 Hz), 8.41 d (1H, 4-H, J =
7.9 Hz), 8.56 s (1H, 2-H), 10.88 s (1H, NH), 13.30 s
(1H, 4″-H), 14.56 s (1H, 4′-OH). Found, %: C 60.09;
H 3.40; N 14.00. C25H17N5O7. Calculated, %: C 60.12;
H 3.43; N 14.02.
N-[2,4-Dihydroxy-2-(4-methylphenyl)-5-oxo-3-
(3-oxo-3,4-dihydroquinoxalin-2-yl)-2,5-dihydro-1H-
pyrrol-1-yl]-2-hydroxybenzamide (IIId). Yield 70%,
mp 153–155°C (from toluene). IR spectrum, ν, cm–1:
3355, 3247 (OH, NH); 1742 (C5=O); 1680 (C3′=O);
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 3 2011

MASHEVSKAYA et al.
420
1638 (C=O, amide). 1H NMR spectrum, δ, ppm: 2.52 s
(3H, Me), 6.70 s (1H, 2-OH), 6.89–7.57 m (12H,
3150 (OH, NH); 1730 (C5=O); 1680 (C3′=O); 1660
(C=O, amide). 1H NMR spectrum, δ, ppm: 7.05 s (1H,
2-OH), 7.30–8.13 m (13H, Harom), 10.51 s (1H, NH),
13.33 s (1H, 4′-H), 14.70 s (1H, 4-OH). Found, %:
C 60.22; H 3.31; N 14.09. C25H17N5O7. Calculated, %:
C 60.12; H 3.37; N 14.02.
H
arom), 7.82 d (1H, 8′-H, J = 7.4 Hz), 10.13 s (1H,
NH), 11.50 s (1H, OH), 13.28 s (1H, 4′-H), 14.52 s
(1H, 4-OH). Found, %: C 64.43; H 4.12; N 11.53.
C25H20N4O6. Calculated, %: C 64.46; H 4.16; N 11.57.
N-[2-(4-Chlorophenyl)-2,4-dihydroxy-5-oxo-3-
(3-oxo-3,4-dihydroquinoxalin-2-yl)-2,5-dihydro-1H-
pyrrol-1-yl]benzamide (IIIe). Yield 68%, mp 212–
213°C (from MeCN). IR spectrum, ν, cm–1: 3390,
3150 (OH, NH); 1730 (C5=O); 1710 (C3′=O), 1643
(C=O, amide). 1H NMR spectrum, δ, ppm: 6.76 s (1H,
2-OH), 7.24–7.76 m (13H, Harom), 10.44 s (1H, NH),
13.29 s (1H, 4′-H), 14.62 s (1H, 4-OH). Found, %:
C 61.52; H 3.29; Cl 7.24; N 11.45. C25H16ClN4O5. Cal-
culated, %: C 61.55; H 3.31; Cl 7.27; N 11.48.
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (project no. 2.19.10).
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pyrrol-1-yl]-2-hydroxybenzamide (IIIf). Yield 68%,
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pyrrol-1-yl]benzamide (IIIg). Yield 70%, mp 189–
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