Five-membered 2,3-dioxo heterocycles: CI. Reaction of 3-aroylpyrrolo[2,1-c] [1,4]benzoxazine-1,2,4-triones with arylhydrazines. Crystal and molecular structure of substituted 2-hydrazonopyrrolo[2,1-c][1,4]benzoxazine

Article abstract of DOI:10.1134/S107042801403021X

A new direction of nucleophilic attack was revealed in the reactions of 3-aroylpyrrolo[2,1-c][1,4]-benzoxazine-1,2,4-triones with o-tolylhydrazine and 2-hydrazinylbenzoic acid hydrochloride, which afforded the corresponding hydrazones at the C²=O carbonyl group, substituted 2-(2-o-tolylhydrazono)pyrrolo[2,1-c]-[1,4]benzoxazine-1,4(2H)-diones and pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidenehydrazinylbenzoic acids. The structure of (Z)-2-{2-[3-benzoyl-1,4-dioxo-1H-pyrrolo[2,1-c][1,4]benzoxazin- 2(4H)-ylidene]hydrazinyl}-benzoic acid was determined by X-ray analysis.

Full text of DOI:10.1134/S107042801403021X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 3, pp. 425–428. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © I.V. Mashevskaya, N.V. Suchkova, L.V. Kuslina, P.A. Slepukhin, A.N. Maslivets, 2014, published in Zhurnal Organicheskoi Khimii,
2014, Vol. 50, No. 3, pp. 437–439.
Five-Membered 2,3-Dioxo Heterocycles: CI.* Reaction
of 3-Aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones
with Arylhydrazines. Crystal and Molecular Structure
of Substituted 2-Hydrazonopyrrolo[2,1-c][1,4]benzoxazine
I. V. Mashevskayaa, N. V. Suchkovaa, L. V. Kuslinaa, P. A. Slepukhinb, and A. N. Maslivetsa
a Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. S. Kovalevskoi/Akademicheskaya 22/20, Yekaterinburg, 620990 Russia
Received February 11, 2013
Abstract—A new direction of nucleophilic attack was revealed in the reactions of 3-aroylpyrrolo[2,1-c][1,4]-
benzoxazine-1,2,4-triones with o-tolylhydrazine and 2-hydrazinylbenzoic acid hydrochloride, which afforded
the corresponding hydrazones at the C2=O carbonyl group, substituted 2-(2-o-tolylhydrazono)pyrrolo[2,1-c]-
[1,4]benzoxazine-1,4(2H)-diones and pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidenehydrazinylbenzoic acids.
The structure of (Z)-2-{2-[3-benzoyl-1,4-dioxo-1H-pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidene]hydrazinyl}-
benzoic acid was determined by X-ray analysis.
DOI: 10.1134/S107042801403021X
We previously showed [2] that hetareno[e]pyrrole-
2,3-diones react with both mono- and binucleophiles
according to only two paths of initial nucleophilic
addition, at the carbon atom in position 1 or 3a of the
substrate molecule. Unexpectedly, the reactions of
3-aroylpyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones
with ortho-substituted phenylhydrazines gave products
of nucleophilic attack at the C2 atom, the correspond-
ing arylhydrazones.
a ratio of 1:1 in boiling anhydrous acetonitrile
(1–3 min; TLC and HPLC monitoring). As a result, we
isolated (Z)-2-{2-[3-aroyl-1,4-dioxo-1H-pyrrolo[2,1-c]-
[1,4]benzoxazin-2(4H)-ylidene]hydrazinyl}benzoic
acids IIa, IIc, and IIe and (Z)-3-aroyl-2-(2-o-tolylhy-
drazono)-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,4(2H)-
diones IIb and IId (Scheme 1). Their structure was
confirmed by X-ray analysis of IIa [3] (see figure).
Compounds IIa–IIe are dark red high-melting
crystalline substances which are soluble in DMF and
DMSO, sparingly soluble in alcohols and haloalkanes,
and insoluble in water and saturated hydrocarbons. The
The reactions were carried out by heating 3-aroyl-
pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones Ia–Ic
with 2-hydrazinylbenzoic acid or o-tolylhydrazine at
Scheme 1.
O
COAr
O
N
O
O
NHNH2
R
N
N
+
COAr
N
·
·
·
H
O
O
R
O
Ia–Ic
IIa–IIe
I, Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4O (c); II, Ar = Ph, R = COOH (a); Ar = 4-MeC6H4, R = Me (b), COOH (c);
Ar = 4-MeOC6H4, R = Me (d), COOH (e).
* For communication C, see [1].
425

MASHEVSKAYA et al.
belonging to the triclinic crystal system. The bond
426
C17
C16
C18
C13
lengths and bond angles in molecule IIa showed no
appreciable differences from the corresponding stand-
ard values. The C1–C2, C3–C4, and C4–C5 bond lengths
in the heteroring are within 1.45(2) Å and are typical
of single bonds in conjugated chains rather than of
classical aromatic bonds. Thus, the examined hetero-
cyclic system should be regarded as heteropolyene
rather than heteroaromatic structure.
The molecular fragment including the heterocycle,
hydrazone moiety, and carboxyphenyl substituent is
planar; deviations of atoms from the mean-square
plane do not exceed 0.250 Å (for O4 in the carboxy
group). Taking into account the extent of this fragment
and its conformational mobility, its fairly planar struc-
ture is determined by formation of bifurcate intra-
molecular hydrogen bond between the N1H proton in
the hydrazone fragment, on the one hand, and carbonyl
oxygen atoms O1 and O4, on the other (see table). The
planar molecular fragments in crystal are packed so
that to form stacks with an interplanar distance of
~3.3 Å, which suggests essential π–π interactions.
O1
C12
C3
C15
O2
C1
C20
C14
N2
C21
O5
C2
C19
C22
C23
C4
O1
C11
N1
C5
C10
C9
N3
C24
C25
C6
C7
O4
O6
C8
Structure of the molecule of (Z)-2-{2-[3-benzoyl-1,4-dioxo-
1H-pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidene]hydra-
zinyl}benzoic acid (IIa) according to the X-ray diffraction
data with atom numbering. Non-hydrogen atoms are shown
as thermal vibration ellipsoids at the 50% probability level.
IR spectra of IIa–IIe contained absorption bands at
3300–3200 cm–1 due to stretching vibrations of the OH
and NH groups and carbonyl absorption bands at
1715–1732 (lactone, COOH in IIa, IIc, IIe), 1662–
1669 (lactam carbonyl involved in intramolecular
hydrogen bond), and 1626–1636 cm–1 (3-C=O). Com-
The benzoyl fragment in molecule IIa is turned
through a dihedral angle of 73.1(2)° (C4C3C12C13) with
respect to the heterocyclic system, and the dihedral
angle between the mean-square planes O3C12C13C3 and
C13C14C15C16C17C18, which characterizes rotation of
the phenyl ring about the carbonyl group, is 29.4(2)°.
As a result, the phenyl ring appears in close proximity
to polar fragments of the neighboring molecule [–x,
2 – y, 1 – z] so that short intermolecular contact
1
pounds IIa–IIe displayed in the H NMR spectra
signals from protons in the aromatic rings and substit-
uents therein, a singlet at δ 14.60–14.97 ppm from
the NH proton, and a broadened singlet at δ 13.60–
13.72 ppm from the COOH proton (IIa, IIc, IIe). The
9-H signal appeared as a doublet in the region δ 8.61–
8.82 ppm due to deshielding effect of the C1=O car-
bonyl group.
H
14A ···O1 2.540 Å is observed. Unfortunately, the
available structural data do not allow us to estimate the
nature of this contact.
The crystal packing of IIa may be described as
layered, where the planar molecular fragments are
oriented approximately parallel to the [15 15 16] plane
while benzoyl fragments deviate from that plane.
Solvation DMF molecules occupy voids in the crystal
packing and are held via intermolecular hydrogen
bonds between the carbonyl group of DMF molecule
and carboxy group of IIa. The crystallographic data
for compound IIa were deposited to the Cambridge
Crystallographic Data Centre (entry no. CCDC
990590; http://www.ccdc.cam.uk).
The structure of compound IIa was determined by
X-ray analysis (see figure). It crystallized as a 1:1
solvate with DMF in the centrosymmetric space group
Parameters of intra- and intermolecular hydrogen bonds in
the crystal structure of (Z)-2-{2-[3-benzoyl-1,4-dioxo-1H-
pyrrolo[2,1-c][1,4]-benzoxazin-2(4H)-ylidene]hydrazinyl}-
benzoic acid (IIa)
d(D–H), d(H···A), ∠DHA, d(D···A),
D–H···A
Å
Å
deg
Å
EXPERIMENTAL
N1–H1···O4
N1–H1···O1
0.956(14) 1.912(14) 135(1) 2.678(2)
0.956(14) 2.117(14) 125(1) 2.778(2)
0.98(2)00 1.60(2)00 163(1) 2.548(2)
The IR spectra were recorded on Perkin Elmer
Spectrum Two and FSM-1201 spectrometers from
samples dispersed in mineral oil. The 1H NMR spectra
O6–H6···O1S
[–x, –y + 2, –z + 1]
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: CI.
427
in isotropic approximation with dependent thermal
parameters. All calculations were performed using
SHELX97 software package [6]. The final divergence
factors were R1 = 0.0394, wR2 = 0.0585 for reflections
with I > 2σ(I) and R1 = 0.1167, wR2 = 0.0625 for
all reflections; goodness of fit S = 1.003; maximum
and minimum residual electron densities 0.178 and
–0.173 ē/Å3.
were measured on a Bruker AM-400 instrument at
400 MHz using DMSO-d6 as solvent and TMS as
reference. The reaction conditions were optimized with
the aid of ultra-HPLC (Waters Acquity UPLC BEH
C18 column, 1.7 μm; eluents methanol–water and
acetonitrile–water, flow rate 0.3–0.5 mL/s; ESI MS
Hevo TQD detector). The purity of the isolated com-
pounds was checked by ultra-HPLC and TLC on
Silufol plates (ethyl acetate, ethyl acetate–benzene,
1:5; development with iodine vapor).
Compounds IIb–IIe were synthesized as described
above for IIa.
(Z)-2-{2-[3-Benzoyl-1,4-dioxo-1H-pyrrolo[2,1-c]-
[1,4]benzoxazin-2(4H)-ylidene]hydrazinyl}benzoic
acid (IIa). A solution of 1.0 mmol of 2-hydrazinyl-
benzoic acid hydrochloride in 30 mL of a 10:1 mixture
of anhydrous acetonitrile and DMSO was added to
a solution of 1.0 mmol of compound Ia in 30 mL of
anhydrous acetonitrile. The mixture was heated for
2 min under reflux and cooled, and the precipitate was
filtered off and recrystallized from acetonitrile. Yield
47%, mp 275–277°C (from MeCN). IR spectrum, ν,
cm–1: 3300 br, 3200 (OH, NH); 1732 (C4=O, COOH),
3-(4-Methylbenzoyl)-2-[2-(2-methylphenyl)-
hydrazono]-1H-pyrrolo[2,1-c][1,4]benzoxazine-
1,4(2H)-dione (IIb). Yield 57%, mp 244–246°C (from
MeCN). IR spectrum, ν, cm–1: 3300 br, 3200 (OH,
NH); 1718 (C4=O); 1669 (C1=O); 1630 (3-C=O).
1H NMR spectrum, δ, ppm: 2.49 s (3H, Me), 2.51 s
(3H, Me), 7.04–8.03 m (11H, Harom), 8.82 d (1H, 9-H,
J = 8.0 Hz), 14.80 s (1H, NH). Found, %: C 71.38;
H 4.37; N 9.59. C26H19N3O4. Calculated, %: C 71.39;
H 4.38; N 9.61.
(Z)-2-{2-[3-(4-Methylbenzoyl)-1,4-dioxo-
1H-pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidene]-
hydrazinyl}benzoic acid (IIc). Yield 54%, mp 282–
284°C (from MeCN). IR spectrum, ν, cm–1: 3300 br,
3200 (OH, NH); 1720 (C4=O, COOH); 1660 (C1=O);
1629 (3-C=O). 1H NMR spectrum, δ, ppm: 2.44 s (3H,
Me), 7.03–8.04 m (11H, Harom), 8.61 d (1H, 9-H, J =
8.0 Hz), 13.70 br.s (1H, COOH), 14.60 s (1H, NH).
Found, %: C 66.79; H 3.65; N 8.97. C26H17N3O6. Cal-
culated, %: C 66.81; H 3.67; N 8.99.
(Z)-3-(4-Methoxybenzoyl)-2-(2-methylphenyl-
hydrazono)-1H-pyrrolo[2,1-c][1,4]benzoxazine-
1,4(2H)-dione (IId). Yield 49%, mp 267–269°C (from
MeCN). IR spectrum, ν, cm–1: 3300 br, 3200 (OH,
NH); 1715 (C4=O); 1667 (C1=O); 1633 (3-C=O).
1H NMR spectrum, δ, ppm: 2.52 s (3H, Me), 3.83 s
(3H, OMe),7.03–8.08 m (11H, Harom), 8.73 d (1H, 9-H,
J = 8.0 Hz), 14.97 s (1H, NH). Found, %: C 69.68;
H 4.10; N 9.02. C27H19N3O5. Calculated, %: C 69.67;
H 4.11; N 9.03.
(Z)-2-{2-[3-(4-Methoxybenzoyl)-1,4-dioxo-
1H-pyrrolo[2,1-c][1,4]benzoxazin-2(4H)-ylidene]-
hydrazinyl}benzoic acid (IIe). Yield 59%, mp 227–
229°C (from MeCN). IR spectrum, ν, cm–1: 3300 br,
3200 (OH, NH); 1710 (C4=O, COOH); 1662 (C1=O);
1626 (3-C=O). 1H NMR spectrum, δ, ppm: 3.86 s (3H,
OMe), 7.03–8.04 m (11H, Harom), 8.63 d (1H, 9-H, J =
8.0 Hz), 13.72 br.s (1H, COOH), 14.80 s (1H, NH).
Found, %: C 64.58; H 3.53; N 8.67. C26H17N3O7. Cal-
culated, %: C 64.60; H 3.54; N 8.69.
1
1669 (C1=O), 1636 (3-C=O). H NMR spectrum, δ,
ppm: 7.23–8.12 m (12H, Harom), 8.63 d (1H, 9-H, J =
8.0 Hz), 13.60 br.s (1H, COOH), 14.87 s (1H, NH).
Found, %: C 66.21; H 3.31; N 9.25. C25H15N3O6. Cal-
culated, %: C 66.23; H 3.33; N 9.27.
The X-ray diffraction data for compound IIa were
acquired on an Xcalibur S (Oxford Diffraction)
automatic four-circle diffractometer with a CCD
detector. The unit cell parameters and experimental
reflection intensities were measured at 295(2) K by
ω/2θ scanning in the range 2.64 < θ < 28.28 with a step
of 1 deg under monochromatized MoKα radiation. Tri-
clinic crystal system, C28H22N4O7, with the following
unit cell parameters: a = 8.463(2), b = 11.609(3), c =
12.8717(19) Å; α = 83.952(16), β = 76.505(17), γ =
85.75(2)°; V = 1221.3(5) Å3; M 526.50; dcalc
=
1.432 g/cm3; Z = 2; space group P-1. Total of
7184 reflection intensities were measured, 5783 of
which were independent (Rint = 0.0304) and 2438 re-
flections were characterized by I > 2σ(I); completeness
0.966 for θ = 26.00°. No correction for absorption was
applied (μ = 0.105 mm–1). The structure was solved by
the direct statistical method and was refined against F2
by the full-matrix least-squares procedure in aniso-
tropic approximation for all non-hydrogen atoms.
Hydrogen atoms in the OH and NH groups were
visualized directly, and their positions were refined
independently; the other hydrogen atoms were placed
in geometrically calculated positions and were refined
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 3 2014

MASHEVSKAYA et al.
428
2. Mashevskaya, I.V. and Maslivets, A.N., Khim. Getero-
This study was performed under financial support
tsikl. Soedin., 2006, p. 3.
by the Ministry of Education and Science of the
Russian Federation, by the Ministry of Education of
Perm Krai (International Research Teams Competi-
tion), and by the Russian Foundation for Basic
Research (project nos. 12-03-00696, 13-03-96009).
3. Kuslina, L.V., Mashevskaya, I.V., Slepukhin, P.A., and
Maslivets, A.N., Russ. J. Org. Chem., 2012, vol. 48,
p. 145.
4. Maslivets, A.N., Mashevskaya, I.V., and Andreichi-
kov, Yu.S., Russ. J. Org. Chem., 1995, vol. 31, p. 569.
5. Altomare, A., Cascarano, G., Giacovazzo, C., and
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