Reactions of 5-aryl-3-arylmethylene substituted 3H-furan-2-ones and 3H-pyrrol-2-ones with acetoacetic ester

Article abstract of DOI:10.1016/j.mencom.2008.05.019

The title reactions afforded ethyl 4-(arylmethylene)-6-oxo-2-aryl-4,5,6,7-tetrahydrobenzofuran-5-carboxylates and ethyl 4-(arylmethylene)-6-oxo-2-aryl-4,5,6,7-tetrahydro-1H-indole-5-carboxylates the structures of which were confirmed by IR and ¹

Full text of DOI:10.1016/j.mencom.2008.05.019

Mendeleev
Communications
Mendeleev Commun., 2008, 18, 167–168
Reactions of 5-aryl-3-arylmethylene substituted
3H-furan-2-ones and 3H-pyrrol-2-ones with acetoacetic ester
Tatyana V. Anis’kova,*a Alevtina Yu. Yegorovaa and Valeriya V. Chadinab
a Department of Chemistry, N. G. Chernyshevsky Saratov State University, 410012 Saratov, Russian Federation.
Fax: +7 8452 51 6960; e-mail: aniskovatv@mail.ru
b Engels Technological Institute, Saratov State Polytechnical University, 413100 Engels, Saratov Region,
Russian Federation
DOI: 10.1016/j.mencom.2008.05.019
The title reactions afforded ethyl 4-(arylmethylene)-6-oxo-2-aryl-4,5,6,7-tetrahydrobenzofuran-5-carboxylates and ethyl
4-(arylmethylene)-6-oxo-2-aryl-4,5,6,7-tetrahydro-1H-indole-5-carboxylates the structures of which were confirmed by IR and
1H NMR spectroscopy.
The synthetic capabilities of 3-arylmethylene-3H-furan(pyrrol)-
2-ones are due to the presence of two electrophilic centres in
their structures. In view of the enonic fragment being fixed in
its S-cis configuration, the above compounds can be used as
acceptors in Michael reaction.
Earlier, Michael condensation has been studied in the
arylmethylene-3H-furan-2-one series with the use of cyclo-
hexanone1 and acetylacetone.2 We used acetoacetic ester as a
C-nucleophile in this interplay. The interaction of 5-aryl-3-aryl-
methylene-3H-furan-2-ones with acetoacetic ester was studied
under conditions of basic catalysis (triethylamine) and with the
use of microwave heating (Scheme1).
the signal of a furan ring proton (compounds 3a–d) is observed
at 5.60–5.66 ppm; the signal of a pyrrole ring (compounds
4a,b) is at 5.80–5.82 ppm; a proton at the N atom manifests
itself by a signal at 8.48–8.50 ppm.
According to the spin–spin coupling constants of methinic
hydrogens 45J 3.53–4.04 Hz (compounds 1a–d, 2a,b), the
dihedral angle g between these hydrogen atoms varied from 48
to 56°.
When acetoacetic ester is used as a reagent, one could
expect an ambiguous course of the reaction. Under basic catalysis
conditions, the reaction did not stop at the formation of 1,5-di-
carbonyl compounds, it produced intramolecular carbocycliza-
tion products; as a result of the dehydration of intermediate B, the
formation of products like D or compounds 3a–d and 4a,b is
possible (Scheme 2). However, according to the above spectral
data, products A and D do not form.
The synthesis under microwave activation can be performed
without a solvent.† In this case, the temperature of the reaction
mixture is not limited by the boiling point of the solvent and the
reaction proceeds much faster. Compounds 1c,d and 2b with an
EtO
Ar
Ar
O
O
O
O
Et3N
OEt
+
R
R
O
X
X
Me
1a–d
2a,b
3a–d
4a,b
1a, 3a Ar = 2-ClC6H4, R = p-Tol, X = O
1b, 3b Ar = 2-O2NC6H4, R = p-Tol, X = O
1c, 3c Ar = 3-MeOC6H4, R = p-Tol, X = O
COOEt
EtO
Ar
Ar
O
O
O
1d, 3d Ar = 3-HO-4-MeOC6H3, R = p-Tol, X = O
Et3N
Me
+
2a, 4a Ar = 3-HO-4-MeOC6H3, R = Ph, X = NH
2b, 4b Ar = 2-ClC6H4, R = p-Tol, X = NH
R
O
R
O
X
X
Me
1a–d
2a,b
Scheme 1
Ethyl-4-(arylmethylene)-6-oxo-2-aryl-4,5,6,7-tetrahydrobenzo-
furan-5-carboxylates 3a–d and ethyl-4-(arylmethylene)-6-oxo-
2-aryl-4,5,6,7-tetrahydro-1H-indole-5-carboxylates 4a,b were
isolated in ~50% yields; their structures were confirmed by IR
and 1H NMR spectroscopy.†
Ar
O
Ar
O
OMe
OEt
R
R
X
X
O
O
O
OH
The IR spectra of compounds 3a–d and 4a,b show a wide
absorption band at 1750–1735 cm–1 caused by the absorption of
ester groups and an absorption band characteristic of a C=O
group at 1730–1715 cm–1.
A
B
Ar
O
O
Ar
O
O
The 1H NMR spectra provide more information; they contain
a set of signals to completely confirm the structures of com-
pounds 3a–d and 4a,b.
OEt
OEt
R
R
X
X
A singlet of methylene protons is detected at 3.80–3.90 ppm
(2H); the signal at 4.83–4.88 ppm corresponds to a proton at
the aromatic substituent (d, 1H, CHAr); the signal of ester
group protons is detected at 3.95–3.99 ppm (d, 1H, CHCOOEt);
D
3a–d
4a,b
Scheme 2
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© 2008 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2008, 18, 167–168
excess of acetoacetic ester were introduced into microwave
synthesis.
The synthesis in a microwave oven allowed us to shorten
the duration of the process by 15 times in comparison with the
usual technique (in an alcohol solution), and the yield of the
final products increased considerably (up to 90%).
The physico-chemical characteristics of the compounds
obtained under classical conditions and on microwave heating
were the same.
†
A Daewoo-KOR 6167 microwave oven (800 W, 2450 MHz) was
employed for microwave syntheses. The IR spectra were measured on a
Specord instrument at 400–4000 cm–1 (in a KBr tablet). The 1H NMR
spectra were recorded on a Bruker-MSL 400 spectrometer (400 MHz) in
[2H6]DMSO; TMS was an internal standard.
5-R-3-arylmethylene-3H-furan-2-ones and 5-R-3-arylmethylene-3H-
pyrrol-2-ones were obtained according to published procedures.3,4
Synthesis of compounds 3a–d and 4a,b.
This work was supported by a grant of the President of the
Russian Federation for Support of Young Russian Scientists
(no. MK-3581.2007.3) and by the Russian Foundation for Basic
Research (grant no. 05-03-32196).
Procedure A. A mixture of 10 mmol of 1a–d or 2a,b, 10 mmol of
acetoacetic ester and 10 mmol of triethylamine was heated in 25 ml
of ethanol for 5 h. Then, the resulting mixture was extracted with a 1:1
mixture of diisopentyl ether and isopropanol. After evaporation, the crystals
obtained were filtered off and recrystallised from isopropanol.
Procedure B. 0.01 mol of 1a–d or 2a,b and 0.03 mol of acetoacetic
ester were thoroughly mixed in a heat-resistant glass. The reaction
mixture was placed in a microwave oven for 10 min at 800 W. The
product was resrystallised from isopropanol.
For 3a: yield 53%, mp 175–177 °C (PriOH). 1H NMR, d: 5.60 (s,
1H), 3.85 (s, 2H, CH2), 4.83 (d, 1H, CH-Ar), 3.95 (d, 1H, CHCOOEt,
45J 3.73 Hz), 1.30 (t, 3H, OCH2Me), 4.12 (m, 2H, OCH2), 6.57–7.48 (m,
8H, Ar), 2.33 (s, 3H, Me-C6H4). Found (%): C, 70.15; H, 5.00. Calc. for
C24H21O4Cl (%): C, 70.50; H, 5.14.
References
1 Z. Yu. Timofeeva and A. Yu. Yegorova, Khim. Geterotsikl. Soedin.,
2007, 823 [Chem. Heterocycl. Compd. (Engl. Transl.), 2007, 43, 690].
2 A. Yu. Yegorova and V. V. Chadina, Khim. Geterotsikl. Soedin., 2007,
1457 [Chem. Heterocycl. Compd. (Engl. Transl.), 2007, 43, 1233].
3 V. A. Sedavkina, N. A. Morozova, A. Yu. Egorova and I. G. Ostroumov,
Khim. Geterotsikl. Soedin., 1987, 451 [Chem. Heterocycl. Compd. (Engl.
Transl.), 1987, 23, 377].
4 A. Yu. Egorova, Izv. Akad. Nauk, Ser. Khim., 2002, 172 (Russ. Chem.
Bull., Int. Ed., 2002, 51, 183).
For 3b: yield 65%, mp 183–185 °C (PriOH). 1H NMR, d: 5.63 (s,
1H), 3.80 (s, 2H, CH2), 4.84 (d, 1H, CH-Ar), 3.95 (d, 1H, CHCOOEt,
45J 3.90 Hz), 1.31 (t, 3H, OCH2Me), 4.14 (m, 2H, OCH2), 6.53–7.50 (m,
8H, Ar), 2.35 (s, 3H, Me-C6H4). Found (%): C, 68.71; H, 5.09; N, 3.94.
Calc. for C24H21NO6 (%): C, 68.73; H, 5.01; N, 3.34.
For 3c: yield 48%, mp 165–168 °C (PriOH). 1H NMR, d: 5.64 (s,
1H), 3.82 (s, 2H, CH2), 4.86 (d, 1H, CH-Ar), 3.96 (d, 1H, CHCOOEt,
45J 3.73 Hz), 1.33 (t, 3H, OCH2Me), 4.15 (m, 2H, OCH2), 6.50–7.45
(m, 8H, Ar), 2.37 (s, 3H, Me-C6H4), 3.73 (s, 3H, OMe). Found (%):
C, 74.08, H, 5.92. Calc. for C25H24O5 (%): C, 74.25; H, 5.94.
For 3d: yield 69%, mp 170–173 °C (PriOH). 1H NMR,
d: 5.66 (s, 1H), 3.83
(s, 2H, CH2), 4.88 (d, 1H, CH-Ar), 3.99 (d, 1H, CHCOOEt, 45J 3.53 Hz),
1.28 (t, 3H, OCH2Me), 4.10 (m, 2H, OCH2), 6.57–7.45 (m, 7H, Ar),
2.31 (s, 3H, Me-C6H4), 3.71 (s, 3H, OMe), 5.05 (s, 1H, OH). Found (%):
C, 71.53; H, 6.02. Calc. for C25H24O6 (%): C, 71.43; H, 5.72.
For 4a: yield 45%, mp 200–203 °C (PriOH). 1H NMR, d: 5.80 (s, 1H),
3.90 (s, 2H, CH2), 4.85 (d, 1H, CH-Ar), 8.48 (s, 1H, NH), 3.97 (d, 1H,
CHCOOEt, 45J 3.90 Hz), 1.31 (t, 3H, OCH2Me), 4.13 (m, 2H, OCH2),
6.59–7.52 (m, 8H, Ar). Found (%): C, 71.47; H, 5.59; N, 3.57. Calc. for
C24H23NO5 (%): C, 71.11; H, 5.68; N, 3.46.
For 4b: yield 49%, mp 198–200 °C (PriOH). 1H NMR, d: 5.82 (s, 1H),
3.86 (s, 2H, CH2), 4.83 (d, 1H, CH-Ar), 8.50 (s, 1H, NH), 3.97 (d,
1H, CH
COOEt, 45J 4.04 Hz), 1.30 (t, 3H, OCH2Me), 4.15 (m, 2H, OCH2),
6.52–7.43 (m, 8H, Ar), 2.40 (s, 3H, Me-C6H4). Found (%): C, 70.75;
H, 5.04; N, 3.16. Calc. for C24H22NO3Cl (%): C, 70.70; H, 5.39; N, 3.44.
Received: 25th September 2007; Com. 07/3018
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