Five-membered 2,3-dioxo heterocycles: XCI. Reaction of 3-aroyl-1H- pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones with dimedone. Crystalline and molecular structure of 3′-benzoyl-4′-hydroxy-1′-(2- hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,

Article abstract of DOI:10.1134/S1070428013010168

3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with 5,5-dimethylcyclohexane-1,3-dione to give 3′-aroyl-4′-hydroxy- 1′-(2-hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3, 2′-pyrrole]-2,4,5′(1′H,5H)-triones. The crystalline and

Full text of DOI:10.1134/S1070428013010168

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 1, pp. 95–98. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © N.M. Tutynina, N.L. Racheva, V.A. Maslivets, Z.G. Aliev, A.N. Maslivets, 2013, published in Zhurnal Organicheskoi Khimii, 2013,
Vol. 49, No. 1, pp. 101–104.
Five-Membered 2,3-Dioxo Heterocycles:
XCI.* Reaction of 3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-
1,2,4-triones with Dimedone. Crystalline and Molecular Structure
of 3′-Benzoyl-4′-hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-
6,7-dihydrospiro[1-benzofuran-3,2′-pyrrole]-
2,4,5′(1′H,5H)-trione
N. M. Tutyninaa, N. L. Rachevaa, V. A. Maslivetsa, Z. G. Alievb, and A. N. Maslivetsa
a Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Institute of Chemical Physics Problems, Russian Academy of Sciences,
Chernogolovka, Moscow oblast, Russia
Received December 17, 2011
Abstract—3-Aroyl-1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones reacted with 5,5-dimethylcyclohexane-
1,3-dione to give 3′-aroyl-4′-hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-
pyrrole]-2,4,5′(1′H,5H)-triones. The crystalline and molecular structures of 3′-benzoyl-4′-hydroxy-1′-(2-hy-
droxyphenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-pyrrole]-2,4,5′(1′H,5H)-trione were determined
by X-ray analysis.
DOI: 10.1134/S1070428013010168
Nucleophilic heterocyclizations and recyclizations
of 1H-pyrrole-2,3-diones fused at the C5–N1 bond to
other heterocyclic systems in reactions with difunc-
tional nucleophiles provide convenient synthetic routes
to various five-, six-, and seven-membered nitrogen-
containing heterocycles, as well as fused, bridged, and
spiro heterocyclic systems [2, 3].
in solution as enol tautomer with fixed cis orientation
of the hydroxy group and hydrogen atom at the double
bond and is capable of acting as 1,3-C,O-binu-
cleophile.
The reactions of 3-aroyl-1H-pyrrolo[2,1-c][1,4]-
benzoxazine-1,2,4-triones Ia–If with dimedone (II)
were carried out by heating equimolar amounts of the
reactants in boiling anhydrous benzene over a period
of 10–50 min (until disappearance of dark violet color
typical of initial pyrrolobenzoxazinetriones). The prod-
ucts were assigned the structure of 3′-aroyl-4′-hy-
droxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-6.7-dihydro-
spiro[1-benzofuran-3,2′-pyrrole]-2,4,5′(1′H,5H)-tri-
ones IIIa–IIIf** (Scheme 1) on the basis of the X-ray
diffraction data for compound IIIa.
Compounds IIIa–IIIf were isolated as high-melting
colorless crystalline substances, which were readily
soluble in DMF and DMSO, poorly soluble in other
organic solvents, and insoluble in water and saturated
hydrocarbons. They showed a positive test (cherry
We previously described recyclizations of 3-acyl-
1H-pyrrolo[2,1-c][1,4]benzoxazine-1,2,4-triones I by
the action of 1,4-N,N- [4, 5], 1,4-S,N- [6], and
1,3-C,N-binucleophiles [7], which involved successive
attacks by the two nucleophilic centers on the C3a
carbon atom and C4 carbonyl carbon atom in molecule
I. The reactions with N,N- and S,N-binucleophiles
were accompanied by cleavage of the oxazine and
pyrrole rings at the C4–O5 and N10–C3a bonds. In con-
tinuation of our studies on nucleophilic recyclizations
of pyrrolobenzoxazinetriones in the present work we
examined their reaction with 5,5-dimethylcyclohex-
ane-1,3-dione (dimedone). Dimedone is known to exist
* For communication XC, see [1].
** For preliminary communication, see [8].
95

TUTYNINA et al.
96
Scheme 1.
O
N
O
O
O
OH
O
+
Ar
Me
Me
Me
O
O
Me
O
Ia–If
II
Me
Me
HO
Me
Me
O
O
N
O
O
N
O
O
COAr
COR
HO
O
OH
IIIa–IIIf
O
OH
Ar = Ph (a), 4-MeOC6H4 (b), 4-BrC6H4 (c), 4-O2NC6H4 (d), 4-EtOC6H4 (e), 4-FC6H4 (f).
color) for enolic or phenolic hydroxy group on treat-
ment with an alcoholic solution of iron(III) chloride.
methylene groups in the dimedone fragment (δ 1.97–
2.15 and 2.43–2.62 ppm for 7-H and 5-H, respec-
tively), a singlet from the phenolic proton (δ 9.54–
10.16 ppm), and a broadened singlet from the enolic
proton (δ 10.90–11.90 ppm).
The IR spectra of IIIa–IIIf contained absorption
bands due to stretching vibrations of enolic and
phenolic hydroxy groups (one or two broadened bands
at 3183–3490 cm–1), lactone carbonyl group (1820–
1845 cm–1), lactam carbonyl group (1698–1753 cm–1),
and C4=O and aroyl carbonyl groups (one broadened
or two narrow bands in the region 1610–1698 cm–1).
The molecular structure of compound IIIa was
proved by X-ray analysis. Because of a small number
of experimental reflections (<30%) the accuracy in the
determination of interatomic distances did not exceed
0.01 Å; nevertheless, all bond lengths were very con-
sistent with the corresponding standard values [9]. The
structure of molecule IIIa is shown in figure. All
double bonds in molecule IIIa are localized. The
2-hydroxyphenyl substituent is turned about the
N1–C21 bond to form a dihedral angle of 73.4° with
respect to the pyrrole ring plane. As a result, intramo-
lecular steric repulsion between the O7 and O4 atoms is
weakened. The benzoyl fragment is not planar: the
torsion angle O6C14C15C16 is –38.4°, and the O6 atom
deviates from the benzene ring plane by 0.71 Å. The
torsion angle C1C13C14O6 formed by the benzoyl frag-
ment with respect to the pyrrole ring is –14.4°.
Molecules IIIa in crystal are multiplicated through the
symmetry centers with the coordinates 0,0,0 and
0,0,1/2 and are linked by very strong intermolecular
hydrogen bonds O5–H5···O4′ (2.58 Å) and less strong
O7–H7 ···O3′ bonds (2.74 Å), giving rise to infinite
zigzag chains along the c axis.
1
Compounds IIIa–IIIf displayed in the H NMR spec-
tra (DMSO-d6) signals from protons in the aromatic
rings and substituents attached thereto, two singlets
from methyl protons in the dimedone fragment
(δ 0.53–0.91 ppm), two doublets of doublets from two
C9
C6
C5
C4
C10
C7
O1
O2
C3
C8
O6
C14
C2
C16
C1
C17
O3
C23
C24
C22
C25
C18
C21
C13
C12
C15
N1
C20
C19
C26
O7
H7
C11
O5
H5
O4
Presumably, in the first step, dimedone molecule
adds by C2 in the enol form to C3a in molecule I. Next
follows furan ring closure via intramolecular attack by
the enolic OH group on the lactone carbonyl carbon
atom in the benzoxazine fragment and cleavage of the
Molecular structure of 3′-benzoyl-4′-hydroxy-1′-(2-hydroxy-
phenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-
pyrrole]-2,4,5′(1′H,5H)-trione (IIIa) according to the X-ray
diffraction data.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XCI.
97
latter at the C4–O5 bond. The described reaction is
an example of regioselective construction of difficultly
accessible spiro[1-benzofuran-3,2′-pyrrole] system
with various substituents in several positions of both
heterocycles.
single crystals, we failed to obtain a larger number of
significant reflections. No correction for absorption
was introduced (μ = 0.094 mm–1). The structure was
solved by the direct method using SIR92 program [10],
followed by a series of calculations of electron density
maps. Hydrogen atoms were localized on the basis of
geometry considerations. The positions of non-hydro-
gen atoms were refined by the least-squares procedure
in full-matrix anisotropic approximation using
SHELXL-97 software package [11]; the final diver-
gence factors were R1 = 0.0818 and wR2 = 0.2349 for
1123 reflections with I ≥ 2σ(I); goodness of fit 0.865.
EXPERIMENTAL
The IR spectra were recorded from samples dis-
persed in mineral oil on a Perkin Elmer Spectrum Two
1
spectrometer. The H and 13C NMR spectra were
measured on a Bruker WP-400 spectrometer at 400
and 100 MHz, respectively, using DMSO-d6 as solvent
and tetramethylsilane as internal reference. The purity
of the isolated compounds was checked by TLC on
Silufol plates using ethyl acetate–benzene (1:5) or
ethyl acetate as eluent; spots were visualized by treat-
ment with iodine vapor.
Compounds IIIb–IIIf were synthesized according
to a similar procedure.
4′-Hydroxy-1′-(2-hydroxyphenyl)-3′-(4-methoxy-
benzoyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzo-
furan-3,2′-pyrrole]-2,4,5′(1′H,5H)-trione (IIIb).
Yield 93%, mp 210–211°C (from EtOAc). IR spec-
trum, ν, cm–1: 3400 br (OH), 1845 (C2=O), 1750
3′-Benzoyl-4′-hydroxy-1′-(2-hydroxyphenyl)-
6,6-dimethyl-6,7-dihydrospiro[1-benzofuran-3,2′-
pyrrole]-2,4,5′(1′H,5H)-trione (IIIa). A solution of
1.0 mmol of compound Ia and 1.0 mmol of dimedone
(II) in 10 ml of anhydrous benzene was heated for
50 min under reflux. The mixture was cooled, and the
precipitate was filtered off. Yield 94%, mp 208–210°C
(from EtOAc). IR spectrum, ν, cm–1: 3380 br (OH),
1830 (C2=O), 1753 (C5′=O), 1698 and 1613 (C4=O,
1
(C5′=O), 1692 and 1610 (C4=O, 3′-C=O). H NMR
spectrum, δ, ppm: 0.53 s (3H, Me), 0.73 s (3H, Me),
2.06 d.d (2H, 7-H, J = 52.2, 16.6 Hz), 2.51 d.d (2H,
5-H, J = 72.2, 18.7 Hz), 3.83 s (3H, OMe), 6.72–
7.77 m (8H, Harom), 9.54 s (1H, 2″-OH), 10.90 br.s
(1H, 4′-OH). Found, %: C 66.26; H 4.78; N 2.84.
C27H23NO8. Calculated, %: C 66.28; H 4.74; N 2.86.
3′-(4-Bromobenzoyl)-4′-hydroxy-1′-(2-hydroxy-
phenyl)-6,6-dimethyl-6,7-dihydrospiro[1-benzo-
furan-3,2′-pyrrole]-2,4,5′(1′H,5H)-trione (IIIc).
Yield 96%, mp 219–221°C (from EtOAc). IR spec-
trum, ν, cm–1: 3300 br (OH), 1838 (C2=O), 1721
1
3′-C=O). H NMR spectrum, δ, ppm: 0.66 s (3H, Me),
0.89 s (3H, Me), 2.06 d.d (2H, 7-H, J = 52.2, 16.1 Hz),
2.52 d.d (2H, 5-H, J = 70.0, 18.3 Hz), 6.78–7.71 m
(9H, Harom), 10.12 s (1H, 2″-OH), 11.80 br.s (1H,
4′-OH). 13C NMR spectrum, δC, ppm: 191.54 (C4),
188.78 (3′-C=O); 174.28, 171.26, 165.93, 154.01 (C2,
C7a, C5′, C4′); 136.93–111.73 (Carom), 67.26 (Cspiro),
50.24 (C5), 35.86 (C7), 33.40 (C6), 27.91 (Me), 26.57
(Me). Found, %: C 67.90; H 4.65; N 3.08. C26H21NO7.
Calculated, %: C 67.97; H 4.61; N 3.05.
1
(C5′=O), 1655 and 1620 (C4=O, 3′-C=O). H NMR
spectrum, δ, ppm: 0.65 s (3H, Me), 0.89 s (3H, Me),
2.05 d.d (2H, 7-H, J = 55.2, 15.9 Hz), 2.52 d.d (2H,
5-H, J = 71.4, 18.7 Hz), 6.77–7.76 m (8H, Harom),
10.13 s (1H, 2″-OH), 11.89 br.s (1H, 4′-OH). Found,
%: C 57.92; H 3.75; Br 14.87; N 2.70. C26H20BrNO7.
Calculated, %: C 58.02; H 3.73; Br 14.83; N 2.61.
X-Ray diffraction data for compound IIIa. Light
yellow well faceted prisms; C26H21NO7; M 459.44; tri-
clinic crystal system, space group P-1. Unit cell pa-
rameters: a = 12.998(2), b = 9.671(2), c = 9.759(3) Å;
α = 84.19(3); β = 89.73(3), γ = 76.45(3)°; V =
1186.2(4) Å3; Z = 2; dcalc = 1.286 g/cm3. Experimental
reflection intensities were measured on a KM-4
(KUMA DIFFRACTION) automatic four-circle dif-
fractometer with χ-geometry [monochromatized
MoKα irradiation, ω/2Θ scanning to 2Θmax = 50.1°
(85.4%)]. Total of 3597 independent reflections (Rint =
0.0411) were measured, only 1123 of which were
characterized by I ≥ 2σ(I). Because of poor quality of
4′-Hydroxy-1′-(2-hydroxyphenyl)-6,6-dimethyl-
3′-(4-nitrobenzoyl)-6,7-dihydrospiro[1-benzofuran-
3,2′-pyrrole]-2,4,5′(1′H,5H)-trione (IIId). Yield
86%, mp 215–217°C (from MeCN). IR spectrum, ν,
cm–1: 3490, 3289 br (OH); 1820 (C2=O); 1741
1
(C5′=O); 1665 br (C4=O, 3′-C=O). H NMR spectrum,
δ, ppm: 0.67 s (3H, Me), 0.91 s (3H, Me), 2.08 d.d
(2H, 7-H, J = 55.5, 16.2 Hz), 2.54 d.d (2H, 5-H, J =
67.5, 18.2 Hz), 6.78–8.36 m (8H, Harom), 10.16 s (1H,
2″-OH), 11.85 br.s (1H, 4′-OH). Found, %: C 61.87;
H 3.98; N 5.65. C26H20N2O9. Calculated, %: C 61.91;
H 4.00; N 5.55.
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TUTYNINA et al.
3′-(4-Ethoxybenzoyl)-4′-hydroxy-1′-(2-hydroxy-
98
REFERENCES
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Yield 80%, mp 188–190°C (from EtOAc). IR spec-
trum, ν, cm–1: 3183 br (OH), 1840 (C2=O), 1698
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1
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5-H, J = 70.6, 18.7 Hz), 6.78–7.80 m (8H, Harom),
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