Five-membered dioxoheterocycles: XCIX. Reaction of 1-aryl-4-aroyl-5- methoxycarbonyl-1H-pyrrole-2,3-diones with indoles. Crystal and molecular structure of substituted 2-(indol-3-yl)pyrrole

Article abstract of DOI:10.1134/S1070428014020146

1-Aryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones react with indole and 2-methylindole with the formation of methyl 1-aryl-3-aroyl-4-hydroxy-2-(1H- indol-3-yl)-5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylates. Crystal and molecular structure of methyl 3-b

Full text of DOI:10.1134/S1070428014020146

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 2, pp. 225−228. © Pleiades Publishing, Ltd., 2014.
Original English Text © E.S. Denislamova, P.A. Slepukhin, A.N. Maslivets, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 2, pp. 232−235.
Five-Membered Dioxoheterocycles: XCIX.*
Reaction of 1-Aryl-4-aroyl-5-methoxycarbonyl-1Н-pyrrole-2,3-
diones with Indoles. Crystal and Molecular Structure
of Substituted 2-(Indol-3-yl)pyrrole
E. S. Denislamovaa, P. A. Slepukhinb, and A. N. Maslivetsa
aPerm State National Research University, Perm, 614990 Russia
bPostovskii Institute of Organic Synthesis, Ural Branch. Russian Academy of Sciences, Yekaterinburg, Russia
e-mail: koh2@psu.ru
Received December 26, 2012
Abstract—1-Aryl-4-aroyl-5-methoxycarbonyl-1Н-pyrrole-2,3-diones react with indole and 2-methylindole with
the formation of methyl 1-aryl-3-aroyl-4-hydroxy-2-(1H-indol-3-yl)-5-oxo-2,5-dihydro-1Н-pyrrole-2-carboxylates.
Crystal and molecular structure of methyl 3-benzoyl-4-hydroxy-2-(2-methyl-1H-indol-3-yl)-5-oxo-1-phenyl-2,5-
dihydro-1Н-pyrrole-2-carboxylate was examined.
DOI: 10.1134/S1070428014020146
We formerly described spiro-bis-heterocyclizations
of 1-aryl-4-aroyl-5-methoxycarbonyl-1Н-pyrrole-2,3-
diones at the action of acyclic, carbocyclic, and hetero-
cyclic enamines proceeding with the primary addition of
the β-СН group of the enamino fragment to the С5 atom
of pyrroledione followed by the intramolecular cycliza-
tion through the attack of the amino group of the enamino
fragment of enamines on the ester carbonyl group in the
position 5 of pyrrolediones [2–4]. With the goal to prove
the above scheme we chose heterocyclic enamines with
the fixed (Е)-location of the β-СН and NH groups of the
enamino fragment thus excluding their intramolecular
cyclization of the above described type.
soluble in DMSO and DMF, sparingly soluble in alcohols
and haloalkanes, insoluble in water and alkanes, showing
a positive test for enol hydroxy group with the alcohol
solution of iron(III) chloride.
The IR spectra of compounds IIIа–IIIk contain
absorption bands of the stretching vibrations of the
secondary amino group of indole as a narrow peak
(3280–3436 cm–1), of the enol OH group as a broad band
O
Ar1
OH
O
O
R
Ar1
N
H
MeOOÑ
O
IIa, IIb
IIà, IIb
N
Ar2
At boiling 1-aryl-4-aroyl-5-methoxycarbonyl-
1Н-pyrrole-2,3-diones Iа–Ie with indole (IIа) and
2-methylindole (IIb) in 1 : 1 ratio in anhydrous benzene
within 10–20 min (when the intense red color of initial
pyrrolediones disappeared) methyl 1-aryl-3-aroyl-4-
hydroxy-2-(1H-indol-3-yl)-5-oxo-2,5-dihydro-1Н-
pyrrole-2-carboxylates IIIа–IIIk were obtained whose
structure was confirmed by X-ray diffraction (XRD) study
by an example of compound IIIf.
O
MeOOÑ
N
Ar2
N
H
R
_
_
Ia–Ie
Ià Ie
IIIa–IIIk
IIIà IIIk
I, Ar1 = Ph, Ar2 = С6H4Br-4 (а), С6H4Me-4 (b),
С6H4OMe-4 (c); Ar1 = С6H4Br-4, Ar2 = С6H4Me-4 (d);
Ar1 = С6H4Me-4, Ar2 = С6H4OMe-4 (е); II, R = H (a),
Me (b); III, R = H: Ar1 = Ph, Ar2 = С6H4Br-4 (а),
С6H4Me-4 (b), С6H4OMe-4 (c); Ar1 = С6H4Br-4, Ar2 =
С6H4Me-4 (d); Ar1 = С6H4Me-4, Ar2 = С6H4OMe-4 (е);
R = Me:Ar1 =Ar2 = Ph (f);Ar1 = Ph,Ar2 = С6H4Br-4 (g),
С6H4Me-4 (h), С6H4OMe-4 (i); Ar1 = С6H4Br-4, Ar2 =
С6H4Me-4 (j); Ar1 = С6H4Me-4, Ar2 = С6H4OMe-4 (k).
Compounds IIIа–IIIk are colorless or light-yellow
crystalline substances of high melting points, readily
_____________
* For Communication XCVIII, see [1].
225

DENISLAMOVA et al.
226
(3141–3280 cm–1), of methoxycarbonyl group (1731–
1764 cm–1), lactam carbonyl group (1686–1705 cm–1),
and aroyl carbonyl group in the region 1652–1674 cm–1.
mulls in mineral oil. 1Н NMR spectra were registered on a
spectrometer Bruker WP-400 in DMSO-d6, internal refer-
ence TMS. The homogeneity of compounds obtained was
checked by TLC on Silufol plates, eluent ethyl acetate,
development in iodine vapor.
1
In the Н NMR spectra of solutions of compounds
IIIа–IIIe in DMSO-d6 along with proton signals of the
aromatic rings and of groups bound to them signals are
observed from the protons of the methoxycarbonyl group
(3.74–3.76 ppm), the doublet of the indole proton H2
(7.86–7.92 ppm), doublet of the proton of indole amino
group (11.11–11.21 ppm), and the broadened singlet of
the proton of OH group at 12.23–12.56 ppm.
Methyl 3-benzoyl-1-(4-bromophenyl)-4-hydroxy-
2-(1H-indol-3-yl)-5-oxo-2,5-dihydro-1Н-pyrrole-
2-carboxylate (IIIа). A solution of 1 mmol of com-
pound Ia and 1 mmol of pyrazole (IIa) in 10 mL of
anhydrous benzene was boiled for 15 min, coоled, the
separated precipitate was filtered off. Yield 91%, mp
235–236°C (decomp., benzene). IR spectrum, ν, cm–1:
3356 (NH), 3189 br (ОН), 1755 (СООMе), 1693 (С2=О),
1
In the Н NMR spectra of solutions of compounds
IIIf–IIIk in DMSO-d6 along with proton signals of the
aromatic rings and of groups bound to them the following
signals are present: a singlet of methyl protons of the
2-methylindole fragment (1.92–2.03 ppm), a singlet of the
protons of the methoxycarbonyl group (3.50–3.54 ppm),
a singlet of the proton of indole amino group (10.98–
11.07 ppm), and a broadened singlet of the hydroxy group
proton in the region 11.70–12.13 ppm.
1
1668 (СОPh). Н NMR spectrum, δ, ppm: 3.76 s (3Н,
СООMе), 7.02–7.55 group of signals (13Н, Ph + 2C6H4),
7.92 d (1Н, H2indole, J 2.2 Hz), 11.21 d (1Н, NH, J 2.2 Hz),
According to XRD data compound IIIf crystallized
in a centrosymmetric space group (Fig. 1). The bond
lengths and bond angles in the molecule are close to
standard values. The dihydropyrrole fragment of the
molecule is flat within 0.016 Å. The phenyl and benzoyl
substituents are turned at considerable angles with respect
to the plane of the dihydropyrrole fragment and they are
not involved in the conjugation with this heterocycle.
In the crystal the molecules due to the contacts of the
polar groups form polymeric chains (Fig. 2), and two
types of contacts are present: a strong hydrogen bond of
a “dimer” type between the carboxy groups and weaker
interactions between the indole ring and the carbonyl of
the benzoyl group C=O⋯H–N (–х, –у, –z). Evidently just
this interaction governs the conformation of the benzoyl
fragment where the carbonyl is deviated both from the
plane of the dihydropyrrole ring and the plane of the
phenyl substituent.
Fig. 1. General view of the molecule of methyl 3-benzoyl-
4-hydroxy-2-(2-methyl-1H-indol-3-yl)-5-oxo-1-phenyl-2,5-
dihydro-1Н-pyrrole-2-carboxylate (IIIf).
The described reaction confirms the previous assump-
tion that the spiro-bis-heterocyclization of 1-aryl-4-aroyl-
5-methoxycarbonyl-1Н-pyrrole-2,3-diones at the action
of enamines proceeds with the primary addition of β-СН
group of the enamino fragment of enamines to the С5
atom of the pyrrolediones.
EXPERIMENTAL
Fig. 2. Interaction of polar groups in the crystal of methyl
3-benzoyl-4-hydroxy-2-(2-methyl-1H-indol-3-yl)-5-oxo-1-
phenyl-2,5-dihydro-1Н-pyrrole-2-carboxylate (IIIf).
IR spectra of compounds obtained were recorded on
a spectrophotometer Perkin Elmer Spectrum Two from
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FIVE-MEMBERED DIOXOHETEROCYCLES: XCIX.
227
12.41 br.s (1Н, ОН). Found, %: С 61.05; Н 3.58; N 5.29.
С27H19BrN2O5. Calculated, %: С 61.03; Н 3.60; Br 15.04;
N 5.27.
carboxylate (IIIf). Yield 89%, mp 217–218°С (decomp.,
m-xylene–ethyl acetate, 1 : 1). IR spectrum, ν, cm–1:
3436 (NH), 3147 br (ОН), 1764 (СООMе), 1692 (С2=О),
1
1671 (СОPh). Н NMR spectrum, δ, ppm: 1.97 s (3Н,
Compounds IIIb–IIIk were synthesized analogously.
Methyl 3-benzoyl-4-hydroxy-2-(1H-indol-3-yl)-5-
oxo-1-(4-tolyl)-2,5-dihydro-1Н-pyrrole-2-carboxylate
(IIIb). Yield 85%, mp 234–235°С (decomp., benzene).
IR spectrum, ν, cm–1: 3385 (NH), 3141 br (ОН), 1755
(СООMе), 1693 (С2=О), 1664 (СОPh). 1Н NMR spec-
trum, δ, ppm: 2.19 s (3Н, Mе), 3.75 s (3Н, СООMе),
6.91–7.55 group of signals (13Н, Ph + 2C6H4), 7.89 d
(1Н, H2indole., J 2.2 Hz), 11.13 d (1Н, NH, J 2.2 Hz),
12.32 br.s (1Н, ОН). Found, %: С 72.11; Н 4.74; N 6.02.
С28H22N2O5. Calculated, %: С 72.09; Н 4.75; N 6.01.
Mе), 3.52 s (3Н, СООMе), 6.89–7.56 group of signals
(14Н, 2Ph + C6H4), 11.00 s (1Н, NH), 11.92 br.s (1Н,
ОН). Found, %: С 72.11; Н 4.73; N 6.02. С28H22N2O5.
Calculated, %: С 72.09; Н 4.75; N 6.01.
X-ray diffraction analysis of compound IIIf was
carried out on an automatic single crystal diffractometer
Xcalibur 3 at 295(2) K (MoKα-radiation, graphite mono-
chromator, ω/2θ-scanning in the range 2.59° < θ < 26.39°).
Crystallographic data: monoclinic system, a 15.5819(16),
b 9.5948(11), c 17.2380(13) Å, β 115.312(9)°, space group
P21/с, Z 4, dcalc 1.330 g/cm3. Intensity of 11290 reflec-
tions was measured, among them 4585 independent
(Rint 0.0658), in particular, 1760 with I > 2σ(I). The
completeness of the data array for the angles θ < 26.0°
is 96.5%. No correction for extinction was introduced
because of its negligible value (μ 0.092 mm–1). The
structure was solved by the direct method and refined
by least-squares method in the anisotropic-isotropic (for
H atoms) approximation applying the SHELXTL-97 soft-
ware [5]. The position of hydrogen atoms was calculated
geometrically (rider model) save atoms of the NH and
ОН groups whose positions were refined in the isotropic
approximation. The final values of the divergence factors
are as follows: wR2 0.0751, R1 0.0427 for 2926 reflec-
tions with I > 2σ(I) and wR2 0.1193, R1 0.1594 for all
reflections at the quality factor S 1.001. The maximum
and minimum peaks of the residual electron density are
0.324 and –0.286 е Å–3 respectively. The complete set
of crystallographic data was deposited to Cambridge
Crystallographic Data Center (CCDC no. 982524) and
it is available at the address ww.ccdc.cam.ac.uk/conts/
retrieving.html.
Methyl 3-benzoyl-4-hydroxy-2-(1H-indol-3-yl)-1-
(4-methoxyphenyl)-5-oxo-2,5-dihydro-1Н-pyrrole-2-
carboxylate (IIIc). Yield 80%, mp 178–179°С (decomp.,
benzene). IR spectrum, ν, cm–1: 3280 (NH, ОН), 1756
(СООMе), 1705 (С2=О), 1669 (СОPh). 1Н NMR spec-
trum, δ, ppm: 3.66 s (3Н, MеO), 3.76 s (3Н, СООMе),
6.79–7.57 group of signals (13Н, Ph + 2C6H4), 7.88 d
(1Н, H2indole, J 2.2 Hz), 11.13 d (1Н, NH, J 2.2 Hz),
12.34 br.s (1Н, ОН). Found, %: С 69.68; Н 4.59; N 5.83.
С28H22N2O6. Calculated, %: С 69.70; Н 4.60; N 5.81.
Methyl 3-(4-bromobenzoyl)-4-hydroxy-2-(1H-in-
dol-3-yl)-5-oxo-1-(4-tolyl)-2,5-dihydro-1Н-pyrrole-2-
carboxylate (IIId). Yield 91%, mp 201–203°С (decomp.,
benzene). IR spectrum, ν, cm–1: 3460 (NH), 3179 br (ОН),
1754 (СООMе), 1697 (С2=О), 1674 (СОAr). 1Н NMR
spectrum, δ, ppm: 2.19 s (3Н, Mе), 3.75 s (3Н, СООMе),
6.88–7.62 group of signals (12Н, 3C6H4), 7.88 d (1Н,
H2indole, J 2.2 Hz), 11.13 d (1Н, NH, J 2.2 Hz), 12.56 br.s
(1Н, ОН). Found, %: С 61.64; Н 3.89; Br 14.60; N 5.16.
С28H21BrN2O5. Calculated, %: С 61.66; Н 3.88; Br 14.65;
N 5.14.
Methyl 4-hydroxy-2-(1H-indol-3-yl)-3-(4-
methylbenzoyl)-1-(4-methoxyphenyl)-5-oxo-2,5-
dihydro-1Н-pyrrole-2-carboxylate (IIIe). Yield 86%,
mp 217–218°С (decomp., benzene). IR spectrum, ν, cm-1:
3375 (NH), 3128 br (ОН), 1754 (СООMе), 1686 (С2=О),
Methyl 3-benzoyl-1-(4-bromophenyl)-4-hydroxy-
2-(2-methyl-1H-indol-3-yl)-5-oxo-2,5-dihydro-1Н-
pyrrole-2-carboxylate (IIIg). Yield 81%, mp 211–213°С
(decomp., benzene). IR spectrum, ν, cm–1: 3302 (NH),
3165 br (ОН), 1756 (СООMе), 1691 (С2=О), 1671
1
1
1660 (СОAr). Н NMR spectrum, δ, ppm: 2.29 s (3Н,
(СОPh). Н NMR spectrum, δ, ppm: 2.03 s (3Н, Mе),
Mе), 3.66 s (3Н, MеO), 3.74 s (3Н, СООMе), 6.78–7.48
3.53 s (3Н, СООMе), 6.90–7.63 group of signals
(13Н, Ph + 2C6H4), 11.07 с (1Н, NH), 11.96 br.s (1Н,
ОН). Found, %: С 61.65; Н 3.86; Br 14.71; N 5.15.
С28H21BrN2O5. Calculated, %: С 61.66; Н 3.88; Br 14.65;
N 5.14.
group of signals (12Н, 3C6H4), 7.86 d (1Н, H2indole
,
J 2.2 Hz), 11.11 d (1Н, NH, J 2.2 Hz), 12.23 br.s (1Н,
ОН). Found, %: С 70.16; Н 4.85; N 5.65. С29H24N2O6.
Calculated, %: С 70.15; Н 4.87; N 5.64.
Methyl 3-benzoyl-4-hydroxy-2-(2-methyl-1H-
indol-3-yl)-5-oxo-1-phenyl-2,5-dihydro-1Н-pyrrole-2-
Methyl 3-benzoyl-4-hydroxy-2-(2-methyl-1H-in-
dol-3-yl)-5-oxo-1-(4-tolyl)-2,5-dihydro-1Н-pyrrole-2-
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DENISLAMOVA et al.
228
Methyl 4-hydroxy-3-(4-methylbenzoyl)-2-(2-
methyl-1H-indol-3-yl)-1-(4-methoxyphenyl)-5-oxo-
2,5-dihydro-1Н-pyrrole-2-carboxylate (IIIk). Yield
80%, mp 217–218°С (decomp., benzene). IR spectrum,
ν, cm–1: 3362 (NH), 3153 br (ОН), 1736 (СООMе), 1694
(С2=О), 1672 (СОAr). 1Н NMR sectrum, δ, ppm: 1.92 s
(3Н, 2-Mе), 2.33 s (3Н, 4-Mе), 3.50 s (3Н, СООMе),
3.68 s (3Н, MеO), 6.72–7.47 group of signals (12Н,
3C6H4), 10.98 с (1Н, NH), 11.70 br.s (1Н, ОН). Found,
%: С 70.60; Н 5.14; N 5.47. С30H26N2O6. Calculated, %:
С 70.58; Н 5.13; N 5.49.
carboxylate (IIIh). Yield 84%, mp 224–225°С (decomp.,
benzene). IR spectrum, ν, cm–1: 3410 (NH), 3152 br (ОН),
1755 (СООMе), 1690 (С2=О), 1667 (СОPh). 1Н NMR
spectrum, δ, ppm: 1.96 s (3Н, Mе), 2.22 s (3Н, Mе), 3.52 s
(3Н, СООMе), 6.76–7.63 group of signals (13Н, Ph +
2C6H4), 10.99 s (1Н, NH), 11.89 br.s (1Н, ОН). Found,
%: С 72.51; Н 5.02; N 5.85. С29H24N2O5. Calculated, %:
С 72.49; Н 5.03; N 5.83.
Methyl 3-benzoyl-4-hydroxy-2-(2-methyl-1H-in-
dol-3-yl)-1-(4-methoxyphenyl)-5-oxo-2,5-dihydro-1Н-
pyrrole-2-carboxylate (IIIi). Yield 91%, mp 231–232°С
(decomp., benzene). IR spectrum, ν, cm–1: 3373 (NH),
3158 br (ОН), 1743 (СООMе), 1691 (С2=О), 1652
(СОPh). 1Н NMR spectrum, δ, ppm: 1.94 s (3Н, 2-Mе),
3.52 s (3Н, СООMе), 3.68 s (3Н, MеO), 6.73–7.56
group of signals (13Н, Ph + 2C6H4), 10.99 s (1Н, NH),
11.89 br.s (1Н, ОН). Found, %: С 70.17; Н 4.86; N 5.63.
С29H24N2O6. Calculated, %: С 70.15; Н 4.87; N 5.64.
ACKNOWLEDGMENTS
The study was carried out under a financial support
of the Ministry of Education and Science of the Russian
Federation, of the Ministry of Education of the Perm
Territory (MIG competition), and of the Russian Foun-
dation for Basic Research (grants nos. 12-03-00696,
13-03-96009).
Methyl 3-(4-bromobenzoyl)-4-hydroxy-2-(2-methyl-
1H-indol-3-yl)-5-oxo-1-(4-tolyl)-2,5-dihydro-1Н-
pyrrole-2-carboxylate (IIIj). Yield 83%, mp 198–199°С
(decomp., benzene). IR spectrum, ν, cm–1: 3422 (NH),
3158 br (ОН), 1731 (СООMе), 1693 (С2=О), 1669
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(СОAr). Н NMR spectrum, δ, ppm: 1.95 s (3Н,
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