Synthesis of new functionally substituted hetarylcarbamates from methyl {4-[(2E)-3-(4-methoxyphenyl)-prop-2-enoyl]phenyl}carbamate

Article abstract of DOI:10.1134/S1070428016120137

Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}- carbamate with ninhydrin and L-proline in methanol–water (10: 1) afforded methyl {4-[1,3-dioxo-1′- (4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′

Full text of DOI:10.1134/S1070428016120137

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 12, pp. 1788–1791. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.V. Velikorodov, N.N. Stepkina, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 12, pp. 1797–1800.
Synthesis of New Functionally Substituted Hetarylcarbamates
from Methyl {4-[(2E)-3-(4-Methoxyphenyl)-
prop-2-enoyl]phenyl}carbamate
A. V. Velikorodov* and N. N. Stepkina
Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia
*e-mail: avelikorodov@mail.ru
Received July 14, 2016
Abstract—Three-component condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}-
carbamate with ninhydrin and L-proline in methanol–water (10:1) afforded methyl {4-[1,3-dioxo-1′-
(4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}carba-
mate. Heating of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-enoyl]phenyl}carbamate with isatin and benzyl-
amine in methanol gave methyl {4-[4′-(4-methoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyr-
rolidin]-3′-ylcarbonyl]phenyl}carbamate. The condensation of methyl {4-[(2E)-3-(4-methoxyphenyl)prop-2-
enoyl]phenyl}carbamate with sarcosine and 11H-indeno[1,2-b]quinoxalin-11-one generated in situ from
ninhydrin and o-phenylenediamine in boiling ethanol led to the formation of methyl {4-[4′-(4-methoxyphenyl)-
1′-methyl-11,11a-dihydro-5aH-spiro[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate.
DOI: 10.1134/S1070428016120137
Multicomponent reactions are a potent tool for the
construction of complex fused and spiro-fused hetero-
cyclic structures [1–3]; among these reactions, those
involving chalcones and chalconoids as one of the
components occupy an important place [4–6].
ylides generated by decarboxylation of α-amino acid
(sarcosine and proline) adducts with ketones (isatin
and ninhydrin). These reactions regioselectively af-
forded the corresponding spiro compounds possessing
a carbamate functionality [7].
We previously studied 1,3-dipolar cycloadditions of
methyl {4-[2-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)-
acetyl]phenyl}carbamate to nonstabilized azomethine
In continuation of studies in this line, in the present
work we examined three-component condensation of
methyl {4-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-
Scheme 1.
O
H
MeO
N
OMe
OH
OH
+
+
COOH
O
N
H
O
O
1
H
MeO
N
O
O
O
MeOH–H2O, 20°C
O
O
OMe
N
O
N
A
2
1788

SYNTHESIS OF NEW FUNCTIONALLY SUBSTITUTED HETARYLCARBAMATES
1789
Scheme 2.
O
H
MeO
N
OMe
NH2
+
+
O
O
N
H
O
1
OMe
Ph
H
MeOH, ∆
O
H
HN
H
O
O
N
N
H
H
OMe
3
phenyl}carbamate (1) [8] with ninhydrin and L-proline
in methanol–water (10:1) at room temperature.
1,3-Dipolar cycloaddition of chlacone 1 and azo-
methine ylide A generated in situ from the amino acid
and ninhydrin afforded 79% of methyl 1,3-dioxo-{4-
[1′-(4-methoxyphenyl)-1,1′,2′,3,5′,6′,7′,7a′-octahydro-
spiro[indene-2,3′-pyrrolizin]-2′-ylcarbonyl]phenyl}car-
bamate (2) with complete regioselectivity (Scheme 1).
stretching vibrations of N–H bonds in the indole frag-
ment, carbamate group, and pyrrolidine ring, respec-
tively. A strong stretching vibration band of the indole
carbonyl group was observed at 1700 cm–1, and the
two other carbonyl bands at 1710 and 1684 cm–1 were
assigned to carbonyl stretching vibrations of the carba-
mate and aroyl groups, respectively.
Compound 3 showed in the 13C NMR spectrum
signals from three carbonyl carbon atoms at δC 154.42
(MeOCONH), 181.72 (C2=O), and 196.74 ppm
(ArC=O) and aromatic carbon signals in the region
δC 108.95–159.14 ppm. The spiro carbon atom resonat-
ed in a weaker field (δC 67.48 ppm) relative to the C3′,
C4′, and C5′ signals of the pyrrolidine ring (δC 67.07,
55.14, and 61.92 ppm, respectively).
1
In the H NMR spectrum of 2, protons of the
pyrrolizidine fragment resonated in the region δ 0.83–
4.92 ppm, and the doublet signal at 4.92 ppm (J =
12 Hz) was assigned to 2′-H in the pyrrolidine ring.
The 1′-H proton gave a multiplet at δ 4.17–4.19 ppm.
Compound 2 displayed in the 13C NMR spectrum
a signal at δC 78.04 ppm due to the spiro carbon atom,
and signals from the carbonyl carbon atoms of the
aroyl group and indandione fragment were located at
δC 196.56, 200.04, and 202.10 ppm, respectively.
1
In the H NMR spectrum of 3, apart from other
proton signals, we observed doublets at δ 4.60 and
5.01 ppm due to 3′-H and 5′-H, respectively, as well as
a triplet at δ 4.03 ppm due to 4′-H. The steric con-
figuration of 3 was determined by two-dimensional
NOESY experiment. The NOESY spectrum revealed
off-diagonal cross-peaks for the 3′-H and 5′-H protons,
which indicated their syn orientation.
It is well known that azomethine ylides can be
generated by reaction of isatins with benzylamine [9].
We studied the three-component condensation of 1
with isatin and benzylamine in boiling methanol. The
[3+2]-cycloaddition was completely regio- and stereo-
selective, and the product was methyl {4-[4′-(4-me-
thoxyphenyl)-2-oxo-5′-phenyl-1,2-dihydrospiro[in-
dole-3,2′-pyrrolidin]-3′-ylcarbonyl]phenyl}carbamate
(3) which was isolated in 80% yield as a single dia-
stereoisomer.
The structure of 3 was confirmed by IR and 1H and
13C NMR spectra, as well as by two-dimensional
NOESY data. The IR spectrum of 3 contained absorp-
tion bands at 3337, 3310, and 3210 cm–1 due to
Compound 1 was also brought into multicomponent
reaction with ninhydrin, o-phenylenediamine, and sar-
cosine in boiling ethanol. Initially, a mixture of nin-
hydrin and o-phenylenediamine was stirred in ethanol
at room temperature for 15 min to generate in situ
11H-indeno[1,2-b]quinoxalin-11-one, compound 1 and
sarcosine were then added, and the resulting mixture
1
was refluxed for 2 h. As shown by H and 13C NMR,
the 1,3-dipolar cycloaddition of chalcone 1 and azo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 12 2016

VELIKORODOV, STEPKINA
1790
Scheme 3.
O
H
MeO
N
OMe
NH2
NH2
H
OH
N
OH
+
+
+
Me
O
OH
O
O
O
1
MeO
O
NH
MeO
HA
HB
H
H
EtOH, ∆
5'
4'
3'
1' N
Me
N
2'
O
N
4
methine ylide formed by decarboxylation of the
11H-indeno[1,2-b]quinoxalin-11-one adduct with
sarcosine was completely regio- and stereoselective,
and it led to the formation of methyl {4-[4′-(4-me-
thoxyphenyl)-1′-methyl-11,11a-dihydro-5aH-spiro-
[benzo[b]phenazine-6,2′-pyrrolidin]-3′-ylcarbonyl]-
phenyl}carbamate 4 in 87% yield.
form. The purity of the isolated compounds was
checked by TLC on Silufol UV-254 plates; spots were
visualized by treatment with iodine vapor.
Methyl {4-[1,3-dioxo-1′-(4-methoxyphenyl)-
1,1′,2′,3,5′,6′,7′,7a′-octahydrospiro[indene-2,3′-pyr-
rolizin]-2′-ylcarbonyl]phenyl}carbamate (2). A mix-
ture of 1.555 g (5 mmol) of methyl {4-[(2E)-3-(4-
methoxyphenyl)prop-2-enoyl]phenyl}carbamate 1 [8],
0.89 g (5 mmol) of ninhydrin, and 0.575 g (5 mmol) of
L-proline was stirred for 1 h in a mixture of 50 mL of
methanol and 5 mL of water; the solvent was removed,
and the residue was purified by descending chromatog-
raphy in a glass column packed with activated silica
(Silica gel 100–400 μm) using ethyl acetate–petroleum
ether (1:1) as eluent. Yield 2.08 g (79%), yellow
crystals, mp 105–106°C. IR spectrum, ν, cm–1: 3320
(NH); 1720, 1680, 1665 (C=O); 1610, 1570, 1565
1
The H NMR spectrum of 4 displayed, apart from
other signals, two triplets at δ 3.71 and 3.99 ppm due
to diastereotopic protons on C5, a multiplet at δ 4.76–
4.78 ppm (4′-H), and a doublet at δ 4.98 ppm (3′-H).
The spiro carbon atom resonated in the 13C NMR spec-
trum of 4 at δC 74.80 ppm.
The steric structure of spiro compound 4 was
determined on the basis of two-dimensional NMR
data. Its HMBC spectrum lacked cross-peaks between
protons on C5′ and carbonyl carbon atom, indicating
that the latter is linked to C3′ rather than C4′. There was
no correlation between 4′-H and 3′-H in the NOESY
spectrum, which is consistent with trans arrangement
of these protons with respect to the pyrrolidine ring.
1
(C=Carom). H NMR spectrum, δ, ppm: 0.83–0.86 m
(1H, CH2), 1.24–1.27 m (1H, CH2), 1.95–1.98 m (1H,
CH2), 2.14–2.17 m (1H, CH2), 2.73–2.77 m (2H, CH2),
3.99–4.06 m (1H, CH2), 4.17–4.19 m (1H, 1′-H),
4.92 d (1H, 2′-H, J = 12 Hz), 3.65 s (3H, OMe), 3.71 s
(3H, CO2Me), 6.92 d (2H, Harom, J = 8.0 Hz), 7.36–
7.50 m (6H, Harom), 7.74 d (2H, Harom, J = 7.6 Hz),
7.86 d (2H, Harom, J = 7.6 Hz), 9.56 br.s (1H, NH).
13C NMR spectrum, δC, ppm: 22.84, 31.40, 53.48
(CH2), 46.48, 60.01, 69.70 (CH), 52.65 (NHCO2Me),
78.04 (Cspiro); 114.20, 118.78, 122.12, 125.59, 128.35,
129.05, 131.05, 134.01, 135.14, 138.46, 142.61,
158.61 (Carom); 154.67 (NHCO2Me), 196.56 (COAr),
200.04, 202.10 (C=O). Found, %: C 70.84; H 5.25;
N 5.15. C31H28N2O6. Calculated, %: C 70.98; H 5.38;
N 5.34.
EXPERIMENTAL
The 1H and 13C NMR and two-dimensional NOESY
and HMBC spectra were recorded on a Bruker DRX
500 spectrometer (500.13 and 126 MHz, respectively)
from solutions in DMSO-d6 using tetramethylsilane as
internal standard. The 13C NMR spectra were recorded
with complete decoupling from protons. The IR
spectra (4000‒400 cm–1) were measured in KBr on
an InfraLUM FT-02 spectrometer with Fourier trans-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 12 2016

SYNTHESIS OF NEW FUNCTIONALLY SUBSTITUTED HETARYLCARBAMATES
1791
Methyl {4-[4′-(4-methoxyphenyl)-2-oxo-
5′-phenyl-1,2-dihydrospiro[indole-3,2′-pyrrolidin]-
3′-ylcarbonyl]phenyl}carbamate (3). A mixture of
0.311 g (1 mmol) of compound 1, 0.147 g (1 mmol) of
isatin, and 0.11 mL (1 mmol) of benzylamine in 25 mL
of methanol was refluxed for 3 h. The solvent was
removed, the solid residue was treated on heating with
30 mL of hexane–ethyl acetate (4:3), and the undis-
solved material was filtered off. Yield 0.46 g (84%),
colorless crystals, mp 228–230°C. IR spectrum, ν,
cm–1: 3337, 3310, 3210 (NH); 1700, 1710, 1684
5a-H), 3.67 s (3H, OMe), 3.71 t (1H, 5′-H, J = 8.5 Hz),
3.73 s (3H, NHCO2Me), 3.99 t (1H, 5′-H, J = 8.8 Hz),
4.76–4.78 m (1H, 4′-H), 4.98 d (1H, 3H, J = 9.3 Hz),
6.68 d (2H, Harom, J = 8.1 Hz), 7.08 d (1H, Harom, J =
8.1 Hz), 7.11–7.24 m (6H, Harom), 7.39 d (1H, Harom
J = 7.7 Hz), 7.60 d (2H, Harom, J = 9.5 Hz), 8.01 d (2H,
arom, J = 8.6 Hz), 8.27 t (2H, Harom, J = 9.6 Hz),
,
H
9.56 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
34.81 (C11), 40.14 (NMe), 44.12 (C4′), 52.65 (CO2Me),
54.00 (OMe), 60.70 (C5a or C11a), 61.74 (C5′), 63.15
(C11a or C5a), 63.90 (C3′), 74.80 (Cspiro); 112.18, 116.49,
118.69, 124.34, 127.37, 128.36, 128.95, 129.38,
128.83, 130.32, 130.40, 132.40, 134.09, 135.80,
138.30, 138.52, 140.92, 159.17 (Carom); 154.96
(CO2Me); 169.18, 170.09 (C=N); 197.85 (CO). Found,
%: C 73.54; H 5.69; N 9.32. C36H34N4O4. Calculated,
%: C 73.70; H 5.84; N 9.55.
1
(C=O); 1610, 1575, 1560 (C=Carom). H NMR spec-
trum, δ, ppm: 3.65 s (3H, OMe), 3.71 s (3H, CO2Me),
3.85 br.s (1H, NH), 4.03 t (1H, 4′-H, J = 10.4 Hz),
4.60 d (1H, 3′-H, J = 10.5 Hz), 5.01 d (1H, 5′-H, J =
10.2 Hz), 6.45 d (2H, Harom, J = 8.1 Hz), 7.12 d (2H,
Harom, J = 8.6 Hz), 7.20–7.41 m (9H, Harom), 7.71 d
(1H, Harom, J = 7.6 Hz), 7.78 t (1H, Harom, J = 7.6 Hz),
8.15 d (2H, Harom, J = 8.6 Hz), 9.54 br.s (1H,
NHCO2Me), 10.40 s (1H, NH). 13C NMR spectrum,
δC, ppm: 52.65 (CO2Me), 54.46 (OMe), 55.14 (C4′),
61.92 (C5′), 67.07 (C3′), 67.48 (Cspiro); 108.95, 112.51,
117.13, 118.54, 121.59, 124.76, 127.14, 127.83,
129.41, 129.65, 130.78, 131.04, 130.94, 131.65,
134.08, 135.11, 137.92, 143.51, 144.23, 159.14 (Carom);
154.42 (NHCO2Me); 181.72, 196.74 (C=O). Found,
%: C 72.14; H 5.37; N 7.60. C33H29N3O5. Calculated,
%: C 72.38; H 5.34; N 7.67.
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (project no. 115021010181).
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Methyl {4-[1′-methyl-4′-(4-methoxyphenyl)-
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(C=O); 1610, 1575, 1565 (C=Carom). H NMR spec-
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 12 2016