Five-membered 2,3-dioxo heterocycles: LXXXIX.* Reaction of methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with (E)-4-Arylaminopent-3-en-2-ones. Crystalline and molecular structure of 9-Acetyl-4-cinnamoyl-3-hydroxy-1-(4-methoxyph

Article abstract of DOI:10.1134/S1070428012100120

Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 4-benzylamino-and 4-arylaminopent-3-en-2-ones to give 1-aryl-7-benzyl- and 1,7-diaryl-9-acetyl-4-cinnamoyl-3-hydroxy-8-methyl-1,7- diazaspiro[4.4]nona-3,8-diene-2,6-dio

Full text of DOI:10.1134/S1070428012100120

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 10, pp. 1329–1332. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © P.S. Silaichev, V.O. Filimonov, P.A. Slepukhin, A.N. Maslivets, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48,
No. 10, pp. 1334–1337.
Five-Membered 2,3-Dioxo Heterocycles: LXXXIX.* Reaction
of Methyl 1-Aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-
2-carboxylates with (E)-4-Arylaminopent-3-en-2-ones.
Crystalline and Molecular Structure of 9-Acetyl-4-cinnamoyl-
3-hydroxy-1-(4-methoxyphenyl)-8-methyl-7-phenyl-
1,7-diazaspiro[4.4]nona-3,8-diene-2,6-dione
P. S. Silaicheva, b, V. O. Filimonovb, P. A. Slepukhinc, and A. N. Maslivetsa, b
a Institute of Natural Sciences, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia
e-mail: koh2@psu.ru
b Perm State National Research University, Perm, Russia
c Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. Akademicheskaya/S. Kovalevskoi 22/20, Yekaterinburg, 620990 Russia
Received July 18, 2011
Abstract—Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 4-ben-
zylamino- and 4-arylaminopent-3-en-2-ones to give 1-aryl-7-benzyl- and 1,7-diaryl-9-acetyl-4-cinnamoyl-3-
hydroxy-8-methyl-1,7-diazaspiro[4.4]nona-3,8-diene-2,6-diones. The crystalline and molecular structures of
9-acetyl-4-cinnamoyl-3-hydroxy-1-(4-methoxyphenyl)-8-methyl-7-phenyl-1,7-diazaspiro[4.4]nona-3,8-diene-
2,6-dione were studied by X-ray analysis.
DOI: 10.1134/S1070428012100120
We previously reported on the reaction of methyl
1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-
2-carboxylates with carbocyclic enamines,
(Z)-3-amino-5,5-dimethyl-cyclohex-2-en-1-ones,
which afforded 1′-aryl-3′-cinnamoyl-4′-hydroxy-6,6-
dimethyl-6,7-dihydrospiro[indole-3,2′-pyrrole]-
2,4,5′(1H,1′H,5H)-triones as a result of attack by the
β-CH and NH groups of the enamine on C2 and ester
carbonyl carbon atom in the dioxopyrrole [2]. Unlike
cyclic enamino ketones, their acyclic analogs exist as
E isomers stabilized by intramolecular hydrogen bond,
which should hamper their reactions as binucleophiles.
Nevertheless, methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-
dihydro-1H-pyrrole-2-carboxylates reacted with
4-arylaminopent-3-en-2-ones and 3-(4-methyl-phe-
nylamino)-1,3-diphenylprop-2-en-1-one to produce
9-acetyl-1,7-diaryl-4-benzoyl-3-hydroxy-8-methyl-1,7-
diazaspiro[4.4]nona-3,8-diene-2,6-diones and 9-acetyl-
1,7-diaryl-4-benzoyl-3-hydroxy-8-phenyl-1,7-diaza-
spiro[4.4]nona-3,8-diene-2,6-diones [3]. Reactions of
methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1H-
pyrrole-2-carboxylates with acyclic enamino ketones
were not reported previously.
By heating equimolar amounts of compounds Ia–Ic
and IIa–IId in boiling anhydrous toluene over a period
of 3–4 h (until the bright red color typical of initial
pyrrolediones I disappeared) we obtained the corre-
sponding 9-acetyl-1,7-diaryl-4-cinnamoyl-3-hydroxy-
8-methyl-1,7-diazaspiro[4.4]nona-3,8-diene-2,6-diones
ІIIa–IIIg in good yields (Scheme 1). Compounds
ІIIa–IIIg were isolated as colorless or light yellow
high-melting crystalline substances; they are readily
soluble in DMF and DMSO, poorly soluble in other
common organic solvents, and insoluble in saturated
hydrocarbons and water; they showed a positive test
for enolic hydroxy group on treatment with an alco-
holic solution of iron(III) chloride.
The IR spectra of IIIa–IIIg contained absorption
* For communication LXXXVIII, see [1].
bands due to stretching vibrations of enolic hydroxy
1329

SILAICHEV et al.
1330
Scheme 1.
Ph
R
Ph
O
O
O
Ph
OH
O
O
O
Me
R
Me
OH
O
MeO
NH
N
R
+
MeO
–MeOH
NH
O
O
O
N
N
N
Me
Me
O
Ar
Ar
Ar
Me
O
O
Me
Ia–Ic
IIa–IId
IIIa–IIIg
І, Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c); ІІ, R = PhCH2 (a), 4-MeC6H4 (b), Ph (c), 4-BrC6H4 (d); ІІІ, Ar = Ph, R = PhCH2 (a),
4-MeC6H4 (b); Ar = 4-MeC6H4, R = Ph (c), 4-BrC6H4 (d); Ar = 4-MeOC6H4, R = PhCH2 (e), Ph (f), 4-MeC6H4 (g).
group (3153–3304 cm–1), lactam carbonyl groups
C6=O and C2=O (1746–1755 and 1707–1725 cm–1),
and ketone carbonyl groups in the acetyl and cin-
namoyl fragments (1665–1678 and 1642–1647 cm–1).
The structure of the synthesized compounds was
confirmed by X-ray analysis of IIIf (see figure).
Compound IIIf crystallized in centrosymmetric space
group, and its molecules are characterized by bond
lengths and bond angles approaching the correspond-
ing standard values. The five-membered pyrrole rings
are planar within 0.01 Å, and the dihedral angle be-
tween their planes is 88.5°. Molecules IIIf in crystal
are linked through intermolecular hydrogen bonds
O3–H3···O2 [–x, –y + 1, –z] [O3–H3 0.85(2), O3···O2
2.713(2) Å, ∠O3H3O2 147(1)°]. The observed short-
ened contact between proton in the benzene ring and
the neighboring carbonyl group C7–H7···O4 [2.638 Å;
–1/2 + x, 1.5 – y, –1/2 + z] is likely to be forced.
Participation of that carbonyl group in intramolecular
hydrogen bond is under discussion, for the O3–N3···O4
angle is too small [107(1)°].
1
In the H NMR spectra of IIIa–IIIg we observed
signals from protons in the aromatic rings and substit-
uents therein, a singlet from the methyl group on C8 at
δ 2.12–2.28 ppm, a singlet from the acetyl protons at
δ 2.12–2.15 ppm, doublets from protons at the exocy-
clic double bond in the cinnamoyl fragment at δ 7.60–
3
7.74 ppm with a coupling constant J of 15.7–16.2 Hz
typical of trans-configured alkenes [4], and a broad-
ened signal from the enolic proton at δ 12.81–
13.13 ppm. Compounds IIIa and IIIe, apart from the
above signals, displayed two doublets at δ 4.74–
4.93 ppm from methylene protons in the benzyl frag-
ment with a geminal coupling constant 2J of 16.7 Hz.
C2
C4
O3
O4
C5
C22
C10
C12
N2
C30
C24
C20
C27
C15
C8
C31
C29
C23
C17
O1
O5
O2
C16
N1
O6
C21
C13
C9
C25
C19
C18
C3
C1
C11
C14
C32
C26
C28
C7
C6
Structure of the molecule of 9-acetyl-4-cinnamoyl-3-hydroxy-1-(4-methoxyphenyl)-8-methyl-7-phenyl-1,7-diazaspiro[4.4]nona-3,8-
diene-2,6-dione (ІІІf) according to the X-ray diffraction data. Non-hydrogen atoms are shown as thermal vibration ellipsoids with
a probability of 50%.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: LXXXIX.
1331
Presumably, compounds IIIa–IIIg are formed via
initial addition of the β-CH group in the enamine frag-
ment of IІa–IId at the C2 carbon atom in the pyrrole
ring of Іa–Ic and subsequent closure of a new pyrrole
ring as a result of nucleophilic attack by the secondary
amino group on the ester carbonyl carbon atom and
elimination of methanol, i.e., according to a scheme
analogous to that proposed in [3].
(4-C=O). 1H NMR spectrum, δ, ppm: 2.12 s (3H, Me),
2.13 s (3H, COMe), 2.34 s (3H, C6H4Me), 7.00–
7.71 m (14H, Harom), 7.66 d (1H, COCH=CHPh, J =
16.2 Hz), 7.74 d (1H, COCH=CHPh, J = 16.2 Hz),
12.88 br.s (1H, OH). Found, %: C 74.16; H 5.01;
N 5.44. C32H26N2O5. Calculated, %: C 74.12; H 5.05;
N 5.40.
9-Acetyl-7-(4-bromophenyl)-4-cinnamoyl-3-hy-
droxy-8-methyl-1-(4-methylphenyl)-1,7-diazaspiro-
[4.4]nona-3,8-diene-2,6-dione (ІІІd). Yield 81%,
mp 222–223°C (from ethyl acetate). IR spectrum, ν,
cm–1: 3310 (OH), 1753 (C6=O), 1713 (C2=O), 1672
EXPERIMENTAL
The IR spectra were recorded on an FSM-1201
spectrometer from samples dispersed in mineral oil.
1
1
(9-C=O), 1642 (4-C=O). H NMR spectrum, δ, ppm:
The H NMR spectra were run on a Bruker AM-400
2.12 s (3H, Me), 2.15 s (3H, COMe), 2.33 s (3H,
C6H4Me), 6.98–7.81 m (13H, Harom), 7.64 d (1H,
C O C H = C H P h , J = 1 5 . 7 H z ) , 7 . 7 2 d ( 1 H,
COCH=CHPh, J = 15.7 Hz), 12.88 br.s (1H, OH).
Found, %: C 64.25; H 4.20; N 4.65. C32H25BrN2O5.
Calculated, %: C 64.33; H 4.22; N 4.69.
spectrometer at 400 MHz using DMSO-d6 as solvent
and tetramethylsilane as internal reference.
9-Acetyl-7-benzyl-4-cinnamoyl-3-hydroxy-8-
methyl-1-phenyl-1,7-diazaspiro[4.4]nona-3,8-diene-
2,6-dione (ІІІa). Compound Іa, 1.0 mmol, was dis-
solved in 15 ml of anhydrous toluene, 1.0 mmol of
enamino ketone IIa in 5 ml of anhydrous toluene was
added, and the mixture was heated for 3 h under reflux.
The mixture was cooled, and the precipitate was
filtered off, and recrystallized from ethyl acetate. Yield
81%, mp 215–217°C. IR spectrum, ν, cm–1: 3179
(OH), 1754 (C6=O), 1721 (C2=O), 1678 (9-C=O),
1645 (4-C=O). 1H NMR spectrum, δ, ppm: 2.13 s (3H,
COMe), 2.28 s (3H, Me), 4.77 d and 4.92 d (1H each,
J = 16.7 Hz), 6.88–7.69 m (15H, Harom), 7.60 d
(1H, COCH=CHPh, J = 16.0 Hz), 7.73 d (1H,
COCH=CHPh, J = 16.0 Hz), 13.08 br.s (1H, OH).
Found, %: C 74.08; H 5.02; N 5.35. C32H26N2O5. Cal-
culated, %: C 74.12; H 5.05; N 5.40.
9-Acetyl-7-benzyl-4-cinnamoyl-3-hydroxy-1-
(4-methoxyphenyl)-8-methyl-1,7-diazaspiro[4.4]-
nona-3,8-diene-2,6-dione (ІІІe). Yield 74%, mp 216–
217°C (from ethyl acetate). IR spectrum, ν, cm–1: 3304
(OH), 1748 (C6=O), 1707 (C2=O), 1669 (9-C=O),
1647 (4-C=O). 1H NMR spectrum, δ, ppm: 2.15 s (3H,
COMe), 2.28 s (3H, Me), 4.74 d and 4.93 d (1H each,
CH2Ph, J = 16.7 Hz), 6.84–7.69 m (14H, Harom) 7.60 d
(1H, COCH=CHPh, J = 15.8 Hz), 7.72 d (1H,
COCH=CHPh, J = 15.8 Hz), 13.13 br.s (1H, OH).
Found, %: C 72.19; H 5.10; N 5.13. C33H28N2O6. Cal-
culated, %: C 72.25; H 5.14; N 5.11.
9-Acetyl-4-cinnamoyl-3-hydroxy-1-(4-methoxy-
phenyl)-8-methyl-7-phenyl-1,7-diazaspiro[4.4]nona-
3,8-diene-2,6-dione (ІІІf). Yield 84%, mp 222–223°C
(from ethyl acetate). IR spectrum, ν, cm–1: 3313 (OH),
1746 (C6=O), 1713 (C2=O), 1671 (9-C=O), 1642
(4-C=O). 1H NMR spectrum, δ, ppm: 2.13 s (3H, Me),
2.14 s (3H, COMe), 3.79 s (3H, OMe), 7.01–7.71 m
(14H, Harom), 7.65 d (1H, COCH=CHPh, J = 15.8 Hz),
7.73 d (1H, COCH=CHPh, J = 15.8 Hz), 12.81 br.s
(1H, OH). Found, %: C 71.81; H 4.93; N 5.22.
C32H26N2O6. Calculated, %: C 71.90; H 4.90; N 5.24.
Compounds IIIb–IIIg were synthesized in a sim-
ilar way.
9-Acetyl-4-cinnamoyl-3-hydroxy-8-methyl-7-
(4-methylphenyl)-1-phenyl-1,7-diazaspiro[4.4]nona-
3,8-diene-2,6-dione (ІІІb). Yield 77%, mp 209–210°C
(from ethyl acetate). IR spectrum, ν, cm–1: 3170 (OH),
1748 (C6=O), 1725 (C2=O), 1665 (9-C=O), 1645
1
(4-C=O). H NMR spectrum, δ, ppm: 2.12 s (6H, Me,
COMe), 2.38 s (3H, C6H4Me), 7.09–7.72 m (14H,
Harom), 7.66 d (1H, COCH=CHPh, J = 16.2 Hz), 7.74 d
(1H, COCH=CHPh, J = 16.2 Hz), 12.97 br.s (1H, OH).
Found, %: C 74.05; H 5.01; N 5.36. C32H26N2O5. Cal-
culated, %: C 74.12; H 5.05; N 5.40.
The X-ray diffraction data for compound IIIf were
acquired on an Xcalibur-3 automatic four-circle dif-
fractometer with a CCD detector [λ(MoKα) 0.71073 Å,
295(2) K, graphite monochromator, ω-scanning
through a step of 1°] from a 0.25 × 0.20×0.15-mm
fragment of a light-yellow prismatic crystal. No cor-
rection for absorption was introduced because of its
smallness (μ = 0.092 mm–1). Total of 16326 reflection
9-Acetyl-4-cinnamoyl-3-hydroxy-8-methyl-1-
(4-methylphenyl)-7-phenyl-1,7-diazaspiro[4.4]nona-
3,8-diene-2,6-dione (ІІІc). Yield 76%, mp 229–230°C
(from ethyl acetate). IR spectrum, ν, cm–1: 3153 (OH),
1748 (C6=O), 1717 (C2=O), 1673 (9-C=O), 1644
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 10 2012

SILAICHEV et al.
1332
1
intensities were measured in the range 2.70 < θ <
(9-C=O), 1642 (4-C=O). H NMR spectrum, δ, ppm:
28.29°; 6549 reflections were independent (Rint
=
2.12 s (3H, Me), 2.13 s (3H, COMe), 2.38 s (3H,
0.0357), and 2608 reflections were characterized by
I > 2σ(I). Completeness 98% for θ < 28.29°. Mono-
clinic crystal system, space group P21/n; unit cell
parameters: a = 9.8107(10), b = 12.6792(11), c =
21.876(2) Å; β = 98.400(9)°. The structure was solved
and refined using SHELXTL 5.1 software package [5].
The positions and temperature parameters of non-
hydrogen atoms were refined first in isotropic and then
in anisotropic approximation by the full-matrix least-
squares procedure against F2. Hydrogen atoms (except
for the OH hydrogen atom) were localized by the
electron density maxima, and their positions were
refined according to the riding model. The position of
the OH hydrogen atom was refined independently in
isotropic approximation. The final divergence factors
were wR2 = 0.0587, R1 = 0.0383 for reflections with
I > 2σ(I) and R1 = 0.1144, wR2 = 0.0621 for all reflec-
tions; goodness of fit S = 1.004. The complete set of
crystallographic data for compound IIIf was deposited
to the Cambridge Crystallographic Data Centre
(entry no. CCDC 900 794) and is available at
www.ccdc.cam.ac.uk/data_request/cif.
C6H4Me), 3.79 s (3H, OMe), 7.01–7.71 m (13H, Harom)
7.65 d (1H, COCH=CHPh, J = 15.9 Hz), 7.73 d (1H,
COCH=CHPh, J = 15.9 Hz), 13.05 br.s (1H, OH).
Found, %: C 72.28; H 5.11; N 5.08. C35H28N2O6. Cal-
culated, %: C 72.25; H 5.14; N 5.11.
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (project no. 2.19.10) and by the
Russian Foundation for Basic Research (project
no.12-03-00696-a).
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9-Acetyl-4-cinnamoyl-3-hydroxy-1-(4-methoxy-
phenyl)-8-methyl-7-(4-methylphenyl)-1,7-diaza-
spiro[4.4]nona-3,8-diene-2,6-dione (ІІІg). Yield
79%, mp 252–253°C (from toluene). IR spectrum, ν,
cm–1: 3196 (OH), 1755 (C6=O), 1713 (C2=O), 1673
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