Five-membered 2,3-dioxo heterocycles: XCIII. Spiro heterocyclization of 4,5-diaroyl-1H-pyrrole-2,3-diones with acyclic enamine. Crystalline and molecular structure of substituted 1,7-diazaspiro[4.4]nonane

Article abstract of DOI:10.1134/S1070428013060109

4,5-Diaroyl-1-aryl-1H-pyrrole-2,3-diones reacted with ethyl 3-amino-3-phenylprop-2-enoate to give ethyl 4-aroyl-1,6-diaryl-3-hydroxy-2-oxo- 8-phenyl-1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carboxylates. The crystalline and molecular structures of ethyl 4-b

Full text of DOI:10.1134/S1070428013060109

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 6, pp. 860–863. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © P.S. Silaichev, N.V. Kudrevatykh, P.A. Slepukhin, A.N. Maslivets, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49,
No. 6, pp. 876–879.
Five-Membered 2,3-Dioxo Heterocycles:
XCIII.* Spiro Heterocyclization of 4,5-Diaroyl-1H-pyrrole-
2,3-diones with Acyclic Enamine. Crystalline and Molecular
Structure of Substituted 1,7-Diazaspiro[4.4]nonane
P. S. Silaicheva, b, N. V. Kudrevatykha, P. A. Slepukhinc, and A. N. Maslivetsa, b
a Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Institute of Natural Sciences, Perm State National Research University,
ul. Genkelya 4, Perm, 614990 Russia
c Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences,
ul. Akademicheskaya/S. Kovalevskoi 22/20, Yekaterinburg, 620990 Russia
Received January 23, 2012
Abstract—4,5-Diaroyl-1-aryl-1H-pyrrole-2,3-diones reacted with ethyl 3-amino-3-phenylprop-2-enoate to
give ethyl 4-aroyl-1,6-diaryl-3-hydroxy-2-oxo-8-phenyl-1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carboxylates.
The crystalline and molecular structures of ethyl 4-benzoyl-3-hydroxy-1-(4-methylphenyl)-2-oxo-6,8-diphenyl-
1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carboxylate were determined by X-ray analysis.
DOI: 10.1134/S1070428013060109
We previously described recyclizations of 4,5-di-
aroyl-1H-pyrrole-2,3-diones with aromatic amines [2]
and substituted hydrazines [3, 4], which involved
successive nucleophilic attacks on C5 and carbonyl
carbon atom of the aroyl group on C4 and led to the
formation of 1,5-diaryl-5-hydroxy-4-(2-aryl-1-aryl-
amino-2-oxoethylidene)pyrrolidine-2,3-diones and
N-aryl-2-(5-aryl-3-aroyl-1H-pyrazol-4-yl)-2-oxoacet-
amides, respectively. There are no published data on
reactions of 4,5-diaroyl-1H-pyrrole-2,3-diones with
1,3-binucleophiles.
By heating equimolar amounts of 4,5-diaroyl-1-
aryl-1H-pyrrole-2,3-diones Ia–If [5] and ethyl
3-amino-3-phenylprop-2-enoate (II) in boiling anhy-
drous benzene for 2–3 h (TLC) we obtained in good
yields the corresponding ethyl 4-aroyl-1,6-diaryl-3-hy-
droxy-2-oxo-8-phenyl-1,7-diazaspiro[4.4]nona-3,6,8-
triene-9-carboxylates IIIa–IIIf (Scheme 1) whose
structure was confirmed by the X-ray diffraction data
for compound IIIb.**
Compounds IIIa–IIIf were isolated as light yellow
high-melting crystalline substances, which were read-
Scheme 1.
O
Ar2
O
Ar2
Ar2
Ar2
O
OH
Ar2
Ar2
OH
O
O
NH2
O
N
+
O
N
–H2O
O
Ph
OEt
N
O
H2N
Ph
Ar1
N
Ar1
O
O
Ar1
EtO
O
Ph
EtO
Ia–If
II
IIIa–IIIf
I, III, Ar2 = Ph, Ar1 = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c); Ar2 = 4-MeC6H4, Ar1 = Ph (d), 4-MeC6H4 (e), 4-MeOC6H4 (f).
* For communication XCII, see [1]. ** For preliminary communication, see [6].
860

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XCIII.
861
ily soluble in DMF, DMSO, chloroform, acetone, and
ethyl acetate, poorly soluble in alcohols and carbon
tetrachloride, and insoluble in saturated hydrocarbons
and water. The products showed a positive color test
(cherry color) for enolic hydroxy group upon treatment
with an alcoholic solution of iron(III) chloride.
C16 C16a, EADP C36 C36a, EADP O5 O5a com-
mands were introduced into the instruction file of the
XL refinement program).
The hydrogen atom in the 3H-pyrrole ring was ex-
pectedly localized on O3 [C23–O3 1.3396(13) Å] rather
than on O2 [O2–C3 1.2203(13) Å; see figure]; it is
involved in intermolecular hydrogen bond with O4
(–x + 1/2, –y + 1/2, –z) in the ethoxycarbonyl group
[O3–H3 0.87(2), O4···H3 1.90(2), O4···O3 2.720(2) Å].
The IR spectra of IIIa–IIIf contained absorption
bands typical of stretching vibrations of enolic hydroxy
group (3170–3292 cm–1) and ester (1715–1725 cm–1),
lactam (C2=O, 1667– 1686 cm–1), and ketone carbonyl
groups (1632–1642 cm–1). Compounds IIIa–IIIf dis-
The benzene solvate molecule occupies a partial
position and is also disordered by two positions. Pre-
sumably, the positions of its disordered components in
the crystal packing are consistent with the disordering
of substituents, otherwise extremely short intermolec-
ular contacts C···H, H···H, and C···C could appear.
1
played in the H NMR spectra signals from protons in
the aromatic rings and substituents attached thereto,
a triplet (δ 1.13–1.15 ppm, CH3) and a multiplet
(δ 4.11– 4.15 ppm, CH2) from the ester ethoxy group,
and a broadened singlet from the enolic hydroxy pro-
ton at δ 12.61–12.80 ppm. In the 13C NMR spectrum of
IIIb we observed signals from carbon atoms in aro-
matic and aliphatic substituent, double-bonded carbon
atoms in the pyrrole rings, carbonyl carbon atoms in
the aroyl and ester groups (δC 187.90 and 161.96 ppm,
respectively), lactam carbonyl carbon atom
(δC 165.77 ppm), C6 (δC 161.73 ppm), and spiro carbon
atom (δC 81.69 ppm).
Compounds IIIa–IIIf are likely to be formed via
addition of the enamine CH group to C5 of pyrrole-2,3-
dione I and subsequent intramolecular cyclization as
a result of nucleophilic attack by the primary amino
group on the carbonyl carbon atom in the aroyl substit-
uent on C5 and elimination of water. The described
reaction is the first example of direct spiro heterocy-
clization of 4,5-diaroyl-1H-pyrrole-2,3-diones with en-
amines, which follows a previously unknown scheme
and yields difficultly accessible spiroheterocyclic
1,7-diazaspiro[4.4]nona-3,6,8-triene system.
Figure shows the structure of compound IIIb deter-
mined by X-ray analysis. Compound IIIb crystallizes
as a 1 :1 solvate with benzene in centrosymmetric
space group belonging to monoclinic crystal system.
Molecule IIIb consists of two spiro-fused pyrrole
rings, one of which is a 3H-pyrrole, and the other,
2,5-dihydro-1H-pyrrole. The bond lengths and bond
angles in molecule IIIb do not differ from the corre-
sponding standard values to an appreciable extent. The
bond angles at the C6 spiro carbon atom range from
100 to 115°, which may be due to distortions intrinsic
to five-membered rings. Molecule IIIb may be regard-
ed as sterically overcrowded; therefore, the planes of
all aryl groups are more or less turned relative to the
pyrrole ring planes. In addition, a serious disordering
of substituents on the 3H-pyrrole ring is observed. In
particular, atoms in both benzene rings are disordered
by two positions with equal populations. The benzene
ring on C2 (see figure) is disordered via rotation about
the C2···C28 axis through an angle of ~66°, and dis-
ordering of the phenyl group on C10 may be described
as libration with respect to the C20–C32 bond (this
disordering is not shown for the sake of simplicity).
Insofar as the coordinates of a number of atoms in the
disordered fragments were fairly similar, some con-
straints were applied to their anisotropic thermal pa-
rameters (ISOR 0.01 C16 C36 O5 C34 C34a, EADP
EXPERIMENTAL
The IR spectra were recorded on a Perkin Elmer
Spectrum Two spectrometer from samples dispersed in
C30
C30A
C28
C15
C37A
C11A
C37
C12
C13
C11
N2
C7
C32
C2
C16
C27
C14A
O1
C14
C29
C10
C6
C22
C20
C4
C5
C8
C35
C1
N1
C31
C33
C19
C23
O5
C21
C17
C25
O2
C9
C3
O4
C26
C34
O3
C36
Ball-and-rod structure of the molecule of ethyl 4-benzoyl-3-
hydroxy-1-(4-methylphenyl)-2-oxo-6,8-diphenyl-1,7-diaza-
spiro[4.4]nona-3,6,8-triene-9-carboxylate (IIIb) according to
the X-ray diffraction data. Hydrogen atoms, except for the
OH hydrogen atom, are not shown for the sake of simplicity.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

SILAICHEV et al.
862
1
mineral oil. The H and 13C NMR spectra were meas-
ured on a Bruker AM-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 using
benzene–ethyl acetate (5:1) as eluent.
20.6818(14) Å; β = 93.674(4)°. The structure was
solved and refined by the full-matrix least-squares
procedure (with respect to F2) in anisotropic approxi-
mation for non-hydrogen atoms using SHELXTL soft-
ware package [7]. Hydrogen atoms attached to carbons
were placed into geometrically calculated positions
and were refined according to the riding model; the
OH hydrogen atom was refined independently in iso-
tropic approximation. The final divergence factors
were R1 = 0.0369, wR2 = 0.0701 for reflections with
I > 2σ(I) and R1 = 0.0781, wR2 = 0.0754 for all reflec-
tions; goodness of fit S = 1.004; completeness 96.9%
(θ < 26.0°); maximum and minimum residual electron
densities 0.204 and –0.207 ēÅ–3. The complete set of
crystallographic data for compound IIb was deposited
to the Cambridge Crystallographic Data Centre
(entry no. CCDC 939281) and is available at
www.ccdc.cam.ac.uk/conts/retrieving.html.
Ethyl 4-benzoyl-3-hydroxy-2-oxo-1,6,8-triphe-
nyl-1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carbox-
ylate (IIIa). A solution of 1.0 mmol of compound Ia
and 1.0 mmol of enamine II in 20 ml of anhydrous
benzene was heated for 2 h under reflux. The mixture
was evaporated by half, an equal volume of petroleum
ether (bp 40–70°C) was added to the residue, the mix-
ture was cooled, and the precipitate was filtered off
and recrystallized from benzene. Yield 71%, mp 195–
196°C. IR spectrum, ν, cm–1: 3170 (OH), 1715 (C=O,
ester), 1686 (C2=O), 1640 (4-C=O). H NMR spec-
1
trum, δ, ppm: 1.14 t (3H, CH2CH3), 4.13 m (2H,
OCH2), 7.03–8.02 m (20H, Ph), 12.80 br.s (1H, OH).
Found, %: C 75.77; H 4.70; N 5.02. C35H26N2O5. Cal-
culated, %: C 75.80; H 4.73; N 5.05.
Ethyl 4-benzoyl-3-hydroxy-1-(4-methoxyphe-
nyl)-2-oxo-6,8-diphenyl-1,7-diazaspiro[4.4]nona-
3,6,8-triene-9-carboxylate (IIIc). Yield 71%,
mp 190–191°C (from benzene). IR spectrum, ν, cm–1:
3292 (OH), 1721 (C=O, ester), 1669 (C2=O), 1632
Compounds IIIb–IIIf were synthesized in a simi-
lar way.
1
(4-C=O). H NMR spectrum, δ, ppm: 1.15 t (3H,
Ethyl 4-benzoyl-3-hydroxy-1-(4-methylphenyl)-
2-oxo-6,8-diphenyl-1,7-diazaspiro[4.4]nona-3,6,8-
triene-9-carboxylate (IIIb). Yield 71%, mp 196–
197°C (from benzene–ethyl acetate, 1:1). IR spectrum,
ν, cm–1: 3265 (OH), 1719 (C=O, ester), 1669 (C2=O),
1640 (4-C=O). 1H NMR spectrum, δ, ppm: 1.14 t (3H,
CH2CH3), 2.21 s (3H, Me), 4.14 m (2H, OCH2), 6.89–
8.00 m (19H, Harom), 12.73 br.s (1H, OH). 13C NMR
spectrum, δC, ppm: 13.67 (CH2CH3), 20.44 (Me),
60.11 (OCH2), 81.69 (C5), 124.83–137.65, 161.73
(C6), 161.96 (C=O, ester), 165.77 (C2), 177.72 (C3),
187.90 (4-C=O). Found, %: C 75.99; H 4.91;
N 4.89. C36H28N2O5. Calculated, %: C 76.04; H 4.96;
N 4.93.
CH2CH3), 3.67 s (3H, OMe), 4.15 m (2H, OCH2),
6.87–8.02 m (19H, Harom), 12.77 br.s (1H, OH). Found,
%: C 73.99; H 4.85; N 4.76. C36H28N2O6. Calculated,
%: C 73.96; H 4.83; N 4.79.
Ethyl 3-hydroxy-4-(4-methylbenzoyl)-6-(4-meth-
ylphenyl)-2-oxo-1,8-diphenyl-1,7-diazaspiro[4.4]-
nona-3,6,8-triene-9-carboxylate (IIId). Yield 76%,
mp 199–200°C (benzene). IR spectrum, ν, cm–1: 3287
(OH), 1721 (C=O, ester), 1678 (C2=O), 1638 (4-C=O).
1H NMR spectrum, δ, ppm: 1.13 t (3H, CH2CH3),
2.35 s (3H, CH3), 2.37 s (3H, CH3), 4.11 m (2H,
OCH2), 7.03–7.92 m (18H, Harom), 12.62 br.s (1H,
OH). Found, %: C 76.25; H 5.21; N 4.78. C37H30N2O5.
Calculated, %: C 76.27; H 5.19; N 4.81.
The X-ray diffraction data for compound IIIb were
acquired at 150(2) K on an Xcalibur S automatic X-ray
diffractometer according to standard procedure
[λMoKα 0.71073 Å, ω-scanning with a step of 1°,
crystal–detector distance 50 mm] from a 0.25×0.20×
0.15-mm light yellow single crystal. Total of 11776 re-
flection intensities were measured in the θ range from
2.89 to 28.28°; 7396 reflections were independent
(Rint = 0.022), and 4357 reflections were characterized
by I > 2σ(I). No correction for absorption was applied.
Monoclinic crystal system, space group C2/c; unit cell
parameters: a = 33.5487(13), b = 9.1118(6), c =
Ethyl 3-hydroxy-4-(4-methylbenzoyl)-1,6-bis(4-
methylphenyl)-2-oxo-8-phenyl-1,7-diazaspiro[4.4]-
nona-3,6,8-triene-9-carboxylate (IIIe). Yield 76%,
mp 215–216°C (from benzene–ethyl acetate, 1:1). IR
spectrum, ν, cm–1: 3269 (OH), 1725 (C=O, ester), 1667
1
(C2=O), 1642 (4-C=O). H NMR spectrum, δ, ppm:
1.14 t (3H, CH2CH3); 2.21 s, 2.35 s, and 2.37 s (3H
each, CH3); 4.11 m (2H, OCH2), 6.89–7.90 m (17H,
H
arom), 12.61 br.s (1H, OH). Found, %: C 76.42;
H 5.39; N 4.67. C38H32N2O5. Calculated, %: C 76.49;
H 5.41; N 4.69.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XCIII.
Ethyl 3-hydroxy-1-(4-methoxyphenyl)-4-(4- REFERENCES
863
methylbenzoyl)-6-(4-methylphenyl)-2-oxo-8-phenyl-
1,7-diazaspiro[4.4]nona-3,6,8-triene-9-carboxylate
(IIIf). Yield 76%, mp 215–216°C (from benzene–ethyl
acetate, 1:1). IR spectrum, ν, cm–1: 3192 (OH), 1719
1. Konovalova, V.V., Stryapunina, O.G., Shklyaev, Yu.V.,
Slepukhin, P.A., and Maslivets, A.N., Russ. J. Org.
Chem., 2013, vol. 49, p. 268.
1
(C=O, ester), 1682 (C2=O), 1636 (4-C=O). H NMR
2. Silaichev, P.S., Kudrevatykh, N.V., Aliev, Z.G., and Mas-
livets, A.N., Russ. J. Org. Chem., 2010, vol. 46, p. 1103.
spectrum, δ, ppm: 1.14 t (3H, CH2CH3), 2.35 s and
2.37 s (3H each, CH3), 3.66 s (3H, OMe), 4.13 m (2H,
OCH2), 6.88–7.92 m (17H, Harom), 12.62 br.s (1H,
OH). Found, %: C 74.41; H 5.24; N 4.59. C38H32N2O6.
Calculated, %: C 74.49; H 5.26; N 4.57.
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5. Silaichev, P.S., Kudrevatykh, N.V., and Maslivets, A.N.,
This study was performed under financial support
by Ministry of Education and Science of the Russian
Federation, by the Ministry of Education of Perm Krai
(International Research Teams Competition), and by
the Russian Foundation for Basic Research (project
nos. 12-03-31157, 12-03-00696).
Russ. J. Org. Chem., 2012, vol. 48, p. 249.
6. Silaichev, P.S., Kudrevatykh, N.V., and Maslivets, A.N.,
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p. 112.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 6 2013