On the reactions of furan-2,3-diones with oxindole (=1,3-dihydro-2h-indol- 2-one) and Lawesson reagent. Synthesis of new 1, 3-dihydro-2H-indol-2-ones, bis-furanones, and bis-pyrrolones

Article abstract of DOI:10.1002/hlca.201000320

Lactone analogues of 3-substituted oxindoles (=1,3-dihydro-2H-indol-2-ones) and nonbenzoid oxa-analogous isoindigoid or nonbenzoid isoindigoid dyes were prepared by the reactions of furan-2,3-diones with oxindole and Lawesson reagent (Schemes 1 and 3), re

Full text of DOI:10.1002/hlca.201000320

Helvetica Chimica Acta – Vol. 94 (2011)
801
On the Reactions of Furan-2,3-diones with Oxindole (¼1,3-Dihydro-2H-
indol-2-one) and Lawesson Reagent. Synthesis of New 1,3-Dihydro-2H-indol-
2-ones, Bis-furanones, and Bis-pyrrolones
˙
by Elif Korkusuz and Ismail Yıldırım*
Department of Chemistry, Faculty of Sciences, Erciyes University, TR-38039 Kayseri
(phone: þ 90-352-4374901/33164; fax: þ 90-352-4374933; e-mail: ismaily@erciyes.edu.tr)
Lactone analogues of 3-substituted oxindoles (¼1,3-dihydro-2H-indol-2-ones) and nonbenzoid oxa-
analogous isoindigoid or nonbenzoid isoindigoid dyes were prepared by the reactions of furan-2,3-diones
with oxindole and Lawesson reagent (Schemes 1 and 3), respectively. So, new derivatives of 2-
oxobutanoic acid, bis-furanone, and bis-pyrrolone, which are potentially biologically active compounds,
were synthesized for the first time.
Introduction. – Polyfunctionalized heterocyclic compounds play important roles in
the drug-discovery process, and an analysis of drugs in late development or on the
market shows that 68% of them are heterocycles [1]. Therefore, much work [2] was
carried out on the reactivity and synthetic potential of 4-acyl-substituted heterocyclic
2,3-diones 1 and 7, particularly on addition of nucleophiles leading to a number of
polyfunctionalized heterocyclic systems [3]. A convenient method for their synthesis,
the mechanism of reactions, and semi-empirical (AM1 and PM3) and ab initio (DFT)
calculations on the interaction of 4-benzoyl-5-phenylfuran-2,3-dione (1a) with several
semicarbazones, ureas, thioureas, anilides, hydrazones, and hydrazines have been
reported recently [4]. As a further development of our continuing studies in this field,
we now report on a new synthetic pathway for the straightforward and effective
preparation of derivatives of 3-substituted oxindoles (¼1,3-dihydro-2H-indol-2-ones)
2 – 5 and oxa analogues of nonbenzoid isoindigoid dyes 6 and 8.
Functionalized oxindoles represent the core structure of many important pharma-
cological agents and natural products [5]. For example, the oxindole motif is present in
the anti-Parkinson drug ropinirole, in nonopioid nociceptin receptor ligands, and in the
growth-hormone secretagogues [6]. Moreover, the oxindole moiety constitutes a key
structural element in several natural products, including the antibiotic speradine and
the cytostatic welwistatin [6]. In addition, the indole moiety is present in a wide variety
of natural and synthetic compounds, many of which have proved to be interesting in a
chemical and biological context because they exhibit a wide spectrum of pharmaco-
logical action [7].
Recently, the reactions of furan-2,3-diones with 2-phenyl-1H-indole to yield
derivatives of indole were reported by S¸ener and co-workers [8a], but they could not
achieve 3-(furan-3-ylidene)-3H-indole derivatives. The reaction of furandiones with
oxindole have not yet been reported. Herein, we report the first synthesis of 3-
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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substituted oxindoles 2 – 5 from the reactions of some furan-2,3-diones 1 with oxindole.
In particular, the compounds 2 were first synthesized by these reactions (Scheme 1),
and the results obtained from all experiments are discussed in this study. Our study also
presents new bis-furanones 6 and bis-pyrrolones 8 representing nonbenzoid oxa
analogues of isoindigoid and nonbenzoid isoindigoid skeletons which are highly
colored products and obtained from the reaction of the furan-2,3-diones 1 with the
Lawesson reagent (see below, Scheme 3).
Scheme 1
a) Reflux in benzene, 24 h. b) EtOH, H2O, KOH, reflux, 1 h. c) reflux in EtOH, H2SO4, 6 h.
Results and Discussion. – Substituted furan-2,3-diones 1a – 1c, which were used as
important starting materials in the synthesis of the target heterocycles, were prepared
by literature procedures [9]. Furandiones show typical reactions of carbonyl
compounds, lactones, and a,b-unsaturated carbonyl compounds, like Michael-type
additions, depending on the structures of the nucleophiles [4][10]. An aldol
condensation of the compounds 1 with oxindole in benzene under reflux for 24 h led
to the formation of corresponding 3-substituted oxindoles 2 and 3, without opening of
the indole ring. Thus the 2H-indol-2-ones 2a – 2c were formed as main products in
moderate yields (39 – 58%), and in addition, 3b and 3c were obtained as by-products in
22% and 30% yields, respectively. The reactions of 1 with oxindole may produce
different oxindole derivatives, e.g., 2 and 3 and their (Z)- and (E)-isomers, via the
reactions at C(3) and C(5) of furandiones 1, respectively. However, our experiments
(TLC studies) resulted in the formation of only two products, the structures of which
were identified as (3E)-3-[4-aroyl-5-aryl-2-oxofuran-3(2H)-ylidene]-1,3-dihydro-2H-

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803
indol-2-one 2 and (4Z)-3-aroyl-4-aryl-4-(1,2-dihydro-2-oxo-3H-indol-3-ylidene]-2-ox-
obutanoic acid 3 (Scheme 1). Alkaline hydrolysis of 2b in 10% KOH/EtOH resulted in
a new product 4b (yellow) in 39% yield (Scheme 1). Additionally, conversion of the 2-
oxobutanoic acids 3b and 3c into their corresponding ester derivatives 5b and 5c was
accomplished by Fischer esterification showing the presence of a free COOH group in
3.
The structures of 2 and 3 were confirmed by analytical and spectroscopic data and
agreed with those found for similar compounds [3][8a][11b]. The configuration of the
C¼C bond between the oxindole and the furan part in compounds 2a – 2c was
established to be (E) by the downfield shifts of the HꢀC(4) resonance (for the atom
numbering, see Scheme 1) of these compounds, which are comparable with those of the
H-atoms for similar (E)-configured isoindigoid derivatives [11]. The IR spectra of 2c
showed absorption bands at 1769, 1700, 1659, and 1598 – 1456 cmꢀ1 due to three C¼O
and aromatic C¼C bonds, respectively. The broad absorption band of the NH group
appeared at 3165 cmꢀ1, and the CꢀOꢀC moiety was observed at 1259 cmꢀ1. The
1H-NMR spectrum of 2c exhibited two sharp s for the MeO groups at d 3.77 and 3.76.
1
The aromatic H-atoms were observed as a set of signals at d 6.80 – 8.73. The H-
decoupled 13C-NMR spectrum of 2c showed 23 resonances, in good agreement with the
proposed structure (see Exper. Part). The 1H- and 13C-NMR spectra of 2a and 2b were
similar to those of 2c, except for the signals of the substituents at C(4’) and C(5’), which
exhibited characteristic resonances with appropriate chemical shifts.
The formation of compounds 3 may be initiated by a Michael addition, via
nucleophilic attack at C(5) of the furan ring of 1 by C(3) of oxindole (Scheme 2).
Rearrangement of the intermediates thus formed may lead to ring opening to give 2-
oxobutanoic acid derivatives 3. In addition, the dark red compounds 2 may be formed
by condensation reactions of oxindole and furandione 1 without opening of the furan or
indole rings [3].
In the 1H-NMR spectra of 2a – 2c, the NH signal revealed the presence of
tautomers 2A – C, the tautomer 2A being the preferred form in (D6)DMSO solution
(Scheme 2), whereas in CDCl3 solutions, the tautomer 2B was predominant. On the
other hand, the products 3b and 3c did not show any tendency to exist in tautomeric
forms 3B and 3C in (D6)DMSO and CDCl3. Similar observations have also been made
with closely related dibenzoylacetic acid, benzoylmalonic acid, dipivaloylacetic acid,
and pivaloylmalonic acid derivatives [10a][10b][10c].
In the UV/VIS spectra of the 3-substituted oxindoles 2a – 2c (Table, Fig.), the broad
lmax1 peaks are characteristic for compounds 2a – 2c and due to pꢀp* electronic
transitions in the oxindole skeleton. The sharp lmax2 peaks at 200 – 320 nm correspond
to nꢀp* electronic transitions of the C¼C, C¼N and C¼O bonds. The lmax1 of 2a at
457 nm undergoes a bathochromic shift to 460 and 485 nm on substitution of the Ph ring
by a Me or MeO group at the para position (Dlmax1 ¼ ꢀ3 nm for 2b and ꢀ 28 nm for
2c), compatible with the fact that the Me and MeO are electron-donor groups.
While examining the melting point of 2a, an uncommon behavior was observed. At
ca. 2258, the dark red crystals in the solid state brightened up into pale red ones before
finally melting at 2608. This obviously indicates an unusual thermal rearrangement
[3b]. Although we have not studied this issue further, we assume that the reaction
occurs under thermodynamic control.

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Scheme 2. Proposal for the Reaction Pathway from 1 to 2 and 3, and Some Tautomeric Forms (2A – C,
3A – C) of 2a – 2c, 3b, and 3c in Solution
To examine if the transformations of the type 1 ! 2 þ 3 can be extended to
somewhat modified systems, several attempts to change the functional groups of 1 were
made, e.g., transformation of the C¼O groups into the corresponding C¼S moieties
with the Lawesson reagent (¼2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane
2,4-disulfide) [12]. Kollenz and co-workers reported that the reaction of compound 1a
with Lawesson reagent yielded the bis-furanone 6a (Ar¼ Ph) instead of the expected
sulfurized product [3] (Scheme 3). Similarly under the usual experimental procedures
for thionation of carbonyl compounds with Lawesson reagent (60 – 708 in dry xylene for
3 h), the furandiones 1b and 1c formed dark red-blue solutions (cf. [3b]) from which,
upon cooling, bright red crystals of 6b and dark-violet crystals of 6c, respectively, were

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805
Figure. UV/VIS Spectra of 2a – 2c in CHCl3
Table. UV/VIS Absorption Maxima of 2a – 2c in CHCl3
a
Ar
lmax1 [nm]
lmax2 [nm]
Absorption shift Dlmax
)
2a
2b
2c
Ph
457
460
485
260
269
270
–
ꢀ 3
4-MeꢀC6H4
4-MeOꢀC6H4
ꢀ 28
a) Dlmax ¼ lmax1(2a) ꢀ lmax1(2b or 2c).
Scheme 3
a) Lawesson reagent, xylene, 60 – 708, 3 h. b) [4f], corresponding N,N-dialkylurea, reflux in benzene, 3 h.
c) Lawesson reagent, xylene, 60 – 708, 2.5 h.
obtained in moderate yields (48 and 52%). The bis-furanones 6b and 6c represent oxa
analogues of isoindigoid derivatives.

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Extending the reaction with Lawesson reagent to the pyrrol-2,3-diones 7, prepared
from cyclocondensation reactions of the corresponding N,N-dialkylureas and 1a [4f],
similar results were achieved: Instead of the expected sulfurized products, again deep
blue isoindigoid dyes 8 were obtained in moderate yields (32 and 36%; Scheme 3). A
close structural similarity of 8 with the long-known Pechmann dyes is obvious [13]. This
analogy, in particular, is also nicely documented by comparing the UV/VIS spectra of 8
and a Pechmann dye, selecting the lmax values (CHCl3) in the VIS region only: lmax of
8a 520 and 550 nm, lmax of 8b 540 and 570 nm, and lmax of Pechmann dye 502 and
538 nm [13a].
Conclusions. – The efficient synthesis of some nonbenzoid oxa analogues of
isoindigoids was reported here. Our current studies suggest that the strategy outlined
herein is rather general and can be successfully applied to the synthesis of a variety of
derivatives containing different oxindole moieties. The biological properties of these
compounds are currently under investigation.
We gratefully acknowledge financial support from the Scientific Research Projects Chairmanship of
Erciyes University.
Experimental Part
General. Compounds 1 were prepared according to [9]. Oxindole, Lawesson reagent, and other
reagents or solvents were purchased from Merck, Fluka, and Sigma, and used without further
purification. TLC: Merck precoated silica gel plates 60 F 254. M.p.: Electrothermal-9200 apparatus;
uncorrected. IR Spectra: Shimadzu-8400 FT-IR spectrometer; ATR ¼ attenuated total reflection; in
cmꢀ1. 1H- and 13C-NMR Spectra: Bruker-Ultrashield spectrometer; at 400.13 (1H) and 100.61 MHz (13C);
in (D6)DMSO and/or CDCl3; d in ppm, J in Hz; when necessary to identify all C-atoms, complementary
NMR experiments (HETCOR, APT, HSQC, and HMBC) were performed. Elemental analyses: Leco-
932-CHNS-O analyzer.
3-Substituted Oxindoles 2 and 3: General Procedure. Compound 1 (1 mmol) and oxindole (1 mmol)
were dissolved in dry benzene (30 ml) and refluxed for 24 h (TLC monitoring). After cooling to r.t., the
yellow precipitate was filtered off and recrystallized from BuOH to give 3 as yellow crystals, and the
remaining soln. was triturated with petroleum ether (40 – 608) to give a crude product that was filtered
and recrystallized from benzene/petroleum ether 4 :1 to give 2 as dark red crystals.
(3E)-3-[4-Benzoyl-2-oxo-5-phenylfuran-3(2H)-ylidene]-1,3-dihydro-2H-indol-2-one (2a). From 1a
(0.28 g): 0.23 g (58%) of 2a. M.p. 2258 (brightening), 2608 (see General Part). UV/VIS: Fig. IR (ATR):
3171 (NH), 1773, 1691, 1659 (C¼O), 1601, 1576, 1533, 1488, 1461, 1450 (C¼C). 1H-NMR ((D6)DMSO)1):
10.64 (s, NH); 8.76 (d, 3J(4,5) ¼ 7.8, HꢀC(4)); 7.95 (dd, 4J(14,16) ¼ 4J(16,18) ¼ 1.3, 3J(14,15) ¼ 3J(17,18) ¼
7.9, HꢀC(14), HꢀC(18)); 7.62 (dd, 4J(8,10) ¼ 4J(10,12) ¼ 1.4, 3J(8,9) ¼ 3J(11,12) ¼ 8.0, HꢀC(8),
HꢀC(12)); 7.58 (m, HꢀC(9), HꢀC(10), HꢀC(11), HꢀC(15), HꢀC(16), HꢀC(17)); 7.35 (dt, 4J(4,6) ¼
1
)
For the arbitrary atom numbering of 2 – 5 and 8, see Scheme 1. The arbitrary atom numbering of 6 is
given below:

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807
1.0, 3J(5,6) ¼ 3J(6,7) ¼ 7.7, HꢀC(6)); 7.04 (dt, 4J(5,7) ¼ 1.0, 3J(4,5) ¼ 3J(5,6) ¼ 7.9, HꢀC(5)); 6.82 (d,
3J(6,7) ¼ 7.8, HꢀC(7)). 13C-NMR ((D6)DMSO)1): 188.23 (PhC¼O); 167.56, 165.96 (C(2), C(2’)); 158.19
(C(5’)); 145.27 (C(7a)); 138.88 (C(6)); 134.06, 133.20 (C(3), C(3’)); 129.33 (C(4)); 132.32, 131.01, 129.12,
128.96, 128.49, 128.02, 127.86, 127.46, 118.85 (8 arom. C, C(4’)); 122.25 (C(5)); 121.57 (C(3a)); 110.71
(C(7)). Anal. calc. for C25H15NO4 (393.39): C 76.33, H 3.84, N, 3.56; found: C 76.43, H 3.80, N 3.65.
(3E)-1,3-Dihydro-3-[4-(4-methylbenzoyl)-5-(4-methylphenyl)-2-oxofuran-3(2H)-ylidene]-2H-indol-
2-one (2b). From 1b (0.31 g): 0.17 g (39%) of 2b. M.p. 282 – 2848. UV/VIS: Fig. IR (ATR): 3174 (NH),
1776, 1719, 1695 (C¼O), 1606, 1574, 1529, 1501, 1462 (C¼C). 1H-NMR ((D6)DMSO)1): 10.60 (s, 0.90 H,
NH, 2A form); 8.74 (d, 3J(4,5) ¼ 7.9, HꢀC(4)); 8.00 (br., 0.10 H, OH, 2B form); 7.85 (d, 3J ¼ 8.0,
3
HꢀC(14), HꢀC(18)); 7.49 (d, J ¼ 8.0, HꢀC(8), HꢀC(12)); 7.35 – 7.19 (m, HꢀC(6), 4 arom. H); 7.03 (t,
3J(4,6) ¼ 7.6, HꢀC(5)); 6.80 (d, 3J(6,7) ¼ 7.6, HꢀC(7)); 2.30, 2.28 (2s, 2 MeC6H4). 13C-NMR
((D6)DMSO)1): 188.13 (ArC¼O); 167.55, 166.08 (C(2), C(2’)); 158.07 (C(5’)); 145.14 (C(7a)); 144.51
(C(6)); 133.12, 132.26 (C(3), C(3’)); 129.42 (C(4)); 129.07, 128.98, 128.76, 128.43, 128.20, 127.89, 126.40,
124.68, 118.44 (8 arom. C, C(4’)); 122.16 (C(5)); 121.66 (C(3a)); 110.63 (C(7)); 21.69, 21.52 (2 MeC6H4).
Anal. calc. for C27H19NO4 (421.44): C 76.95, H 4.54, N 3.32; found: C 76.90, H 4.40, N 3.23.
(3E)-1,3-Dihydro-3-[4-(4-methoxybenzoyl)-5-(4-methoxyphenyl)-2-oxofuran-3(2H)-ylidene]-2H-
indol-2-one (2c). From 1c (0.34 g): 0.25 g (42%) of 2c. M.p. 2508. UV/VIS: Fig. IR (ATR): 3165 (NH),
1769, 1700, 1659 (C¼O), 1598, 1537, 1495, 1456 (C¼C), 1256 (CꢀO). 1H-NMR ((D6)DMSO)1): 10.58 (s,
3
3
3
NH); 8.73 (d, J(4,5) ¼ 8.0, HꢀC(4)); 7.91 (d, J ¼ 8.6, HꢀC(14), HꢀC(18)); 7.60 (d, J ¼ 8.8, HꢀC(8),
HꢀC(12)); 7.40 – 6.89 (m, 6 arom. H); 6.80 (d, 3J ¼ 8.7, HꢀC(7)); 3.77, 3.76 (2s, 2 MeO). 13C-NMR
((D6)DMSO)1): 187.53 (ArC¼O); 167.60, 166.18 (C(2), C(2’)); 157.80 (C(5’)); 163.26, 162.59 (arom. C);
144.93 (C(7a)); 133.45 (C(6)); 132.15, 131.23 (C(3), C(3’)); 129.56 (C(4)); 129.90, 128.48, 127.86, 124.79,
119.67, 115.07, 109.54 (6 arom. C, C(4’)); 122.04 (C(5)); 121.55 (C(3a)); 114.22 (C(7)); 56.00, 55.85
(2 MeO). Anal. calc. for C27H19NO6 (453.44): C 71.52, H 4.22, N 3.09; found: C 71.60, H 4.20, N 2.97.
(4Z)-4-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-3-(4-methylbenzoyl)-4-(4-methylphenyl)-2-oxobuta-
noic Acid (¼(gZ)-g-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-b-(4-methylbenzoyl)-4-methyl-a-oxoben-
zenebutanoic Acid; 3b). From 1b (0.31 g): 0.10 g (22%) of 3b. M.p. 2138. IR (ATR): 3423 (NH), 1767,
1
1726, 1709, 1659 (C¼O), 1618, 1603, 1576, 1551, 1470 (C¼C). H-NMR ((D6)DMSO)1): 11.57 (s, NH);
7.98 (d, 3J ¼ 8.1, HꢀC(4)); 8.00 (s, OH, D2O exchangeable); 7.40 – 6.92 (m, 11 arom. H); 7.30 (s, CH); 2.32,
2.19 (2s, 2 MeC6H4). 13C-NMR ((D6)DMSO)1): 192.43 (C¼O); 191.72 (C¼O); 172.47 (C¼O); 165.12
(C¼O); 146.20, 145.80, 143.70, 143.39, 133.16, 130.57, 130.23, 129.86, 129.30, 128.78, 128.47, 126.41, 126.00,
125.76, 123.29 (C(3a)); 111.13 (C(7)); 66.47 (CH); 21.74, 21.43 (2 MeC6H4). Anal. calc. for C27H21NO5
(439.46): C 73.79, H 4.82, N 3.19; found: C 73.73, H 4.90, N 2.99.
(4Z)-4-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-3-(4-methoxybenzoyl)-4-(4-methoxyphenyl)-2-oxo-
butanoic Acid (¼(gZ)-g-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-b-(4-methoxybenzoyl)-4-methoxy-a-
oxobenzenebutanoic Acid; 3c). From 1c (0.34 g): 0.14 g (30%) of 3c. M.p. 2108. IR (ATR): 3418
1
(NH), 1772, 1719, 1707, 1670 (C¼O), 1612, 1593, 1564, 1506, 1464 (C¼C). H-NMR ((D6)DMSO)1):
11.52 (s, NH); 8.05 (d, 3J ¼ 8.6, HꢀC(4)); 8.07 (s, OH, D2O exchangeable); 7.41 – 6.83 (m, 11 arom. H);
7.33 (s, CH); 3.79, 3.66 (2s, 2 MeO). 13C-NMR ((D6)DMSO)1): 191.99 (C¼O); 191.64 (C¼O); 172.55
(C¼O); 164.94 (C¼O); 163.97, 163.30, 145.07, 143.25, 132.29, 131.13, 130.56, 128.77, 128.53, 126.36, 126.14,
123.47, 123.34, 115.51, 115.03 (arom. C); 111.24 (C(7)); 66.40 (CH); 56.20, 56.02 (2 MeO). Anal. calc. for
C27H21NO7 (471.46): C 68.78, H 4.49, N 2.97; found: C 69.02, H 4.35, N 3.00.
(2E)-2-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-3-(4-methylbenzoyl)-4-(4-methylphenyl)-4-oxobuta-
noic Acid (¼(aE)-a-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-b-(4-methylbenzoyl)-4-methyl-4-oxoben-
zenebutanoic Acid; 4b). A mixure of 2b (0.42 g, 1 mmol) and 10% KOH/EtOH (1.5 ml) was stirred
under reflux for 1 h thus forming an orange precipitate. After cooling to r.t., H2O was added until a clear
yellow soln. was obtained. Acidification with dil. HCl soln. afforded a yellow precipitate 4b (0.17 g,
39%), which by no means could be further purified. M.p. 1598 (! red), 3038. IR (ATR): 3388 (NH),
1776, 1715, 1700, 1669 (C¼O). 1H-NMR ((D6)DMSO)1): 13.40 (br., 0.75 H, COOH, D2O exchangeable);
10.74 (s, NH); 8.03 (d, 3J ¼ 8.0, HꢀC(4)); 7.79 (d, 3J ¼ 7.8, 1 arom. H); 7.60 – 7.04 (2 AA’BB’, 8 arom. H);
6.79 (dd, 3J(4,5) ¼ 3J(5,6) ¼ 7.7, HꢀC(5)); 6.72 (d, 3J(6,7) ¼ 7.8, HꢀC(7)); 5.00 (s, CH); 2.35, 2.23 (2s,
2 Me). 13C-NMR ((D6) DMSO)1): 195.40 (ArC¼O); 169.41 (C¼O, COOH); 169.09 (C(2)); 144.26

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(C(3)); 142.46, 137.78, 134.45, 131.00, 129.86, 129.77, 128.93, 128.76, 128.58, 128.12, 127.04, 124.65; 121.84
(C(3a)); 120.88 (C(5)); 110.33 (C(7)); 103.02 (C(4)); 42.95 (CH); 21.61 (MeC6H4). Anal. calc. for
C27H21NO5 (439.46): C 73.79, H 4.82, N 3.19; found: C 73.80, H 4.88, N 3.39.
Oxindoles 5: General Procedure. To the cold soln. of oxindole 3 in H2SO4 was added a large excess of
EtOH with stirring. Then, the mixture was refluxed on a steam bath for 6 h with stirring. After cooling to
58, the precipitate formed was filtered off and recrystallized from EtOH: ester 5.
Ethyl (4Z)-4-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-3-(4-methylbenzoyl)-4-(4-methylphenyl)-2-
oxobutanoate (5b): From 3b (0.50 g): 0.34 g (64%) of 5b. Yellow crystals. M.p. 1558. IR (ATR): 3287
(NH), 1745, 1720, 1684, 1651 (C¼O). 1H-NMR ((D6)DMSO)1): 12.25 (s, 0.44 H, OH); 10.80 (s, 0.44 H,
NH, enol form); 10.60 (s, 0.56 H, NH, keto form); 8.99 (d, 0.44 H, HꢀC(4)); 8.18 – 6.43 (m, 11.56 H, arom.
H); 7.27 (s, 0.56 H, CH); 3.98 – 3.79 (m, CH2O); 2.41, 2.39, 2.36, 2.31 (4s, 2 Me); 1.25 – 1.06 (m, Me).
13C-NMR ((D6)DMSO): 193.93, 191.91, 189.09 (C¼O); 174.07, 169.50, 167.19, 163.73, 161.04 (C¼O);
148.57, 144.46, 143.87, 143.53, 140.78, 139.96, 139.83, 138.00, 137.45, 134.29, 133.58, 131.85, 131.17, 130.79,
130.23, 130.15, 129.87, 129.66, 129.53, 129.48, 129.33, 128.88, 128.35, 127.95, 127.87, 127.61, 126.88, 122.77,
122.45, 122.32, 122.10, 122.05, 121.61, 121.07, 11.00, 110.57, 109.78 (arom. C); 64.42 (CH); 62.57, 62.17
(CH2O); 21.71, 21.60, 21.35, 21.09 (2 Me); 14.81, 13.91 (MeCH2O). Anal. calc. for C29H25NO5 (467.51): C
74.50, H 5.39, N 3.00; found: C 74.51, H 5.39, N 3.02.
Ethyl (4Z)-4-(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)-3-(4-methoxybenzoyl)-4-(4-methoxyphenyl)-
2-oxobutanoate (5c). From 3c (0.50 g): 0.32 g (60%) of 5c. Orange crystals. M.p. 1688. IR (ATR): 3266
(NH), 1730, 1717, 1686, 1650 (C¼O). 1H-NMR ((D6)DMSO)1): 12.32 (s, 0.48 H, OH); 10.75 (s, 0.48 H,
NH, enol form); 10.65 (s, 0.52 H, NH, keto form); 9.03 (d, 0.48 H, HꢀC(4)); 8.26 – 6.53 (m, 11.52 H, arom.
H); 7.30 (s, 0.52 H, CH); 4.00 – 3.82 (m, CH2O); 3.79, 3.77, 3.75, 3.71 (4s, 2 MeO); 1.24 – 1.01 (m, Me).
13C-NMR ((D6)DMSO): 193.07, 192.68, 189.11 (C¼O); 170.76, 168.89, 164.59, 163.70 (C¼O); 160.10,
159.92, 158.49, 145.57, 145.46, 139.78, 134.19, 133.67, 133.45, 132.00, 131.77, 131.60, 131.20, 130.99, 129.92,
129.46, 129.24, 129.04, 128.70, 128.51, 128.154, 127.60, 124.05, 123.47, 122.84, 122.72, 122.35, 122.07, 121.70,
121.11, 115.30, 114.34, 113.88, 113.75, 113.43, 113.23, 111.33, 110.54 (arom. C); 64.36 (CH); 63.08, 62.87
(CH2O); 56.48, 56.15, 55.65, 55.57 (2 MeO); 14.18, 13.89 (MeCH2O). Anal. calc. for C29H25NO7 (499.51):
C 69.78, H 5.04, N 2.80; found: C 69.81, H 5.06, N 2.97.
Bis-furanones 6 and Bis-pyrrolones 8: General Procedure. Lawesson reagent (0.5 g, 1.1 mmol) and
the corresponding compound 1 or 7 (2 mmol) were kept in dry xylene (10 ml) at 60 – 708 for 3 h (1) or
2.5 h (7). After cooling to r.t., a dark precipitate was filtered off and recrystallized from AcOH to give 6
or 8 as colored crystals, similarly to the literature procedures [3b].
(3E)-4-(4-Methylbenzoyl)-3-[4-(4-methylbenzoyl)-5-(4-methylphenyl)-2-oxofuran-3(2H)-ylidene]-
5-(4-methylphenyl)furan-2(3H)-one (6b): From 1b (0.61 g): 0.31 g (48%) of 6b. Bright red crystals. M.p.
3268 (brightening), 386 – 3908. IR (ATR): 1768, 1666 (C¼O). 1H-NMR (CDCl3)1): 7.89 (d, 3J ¼ 8.1,
3
HꢀC(14), HꢀC(18), HꢀC(14’), HꢀC(18’)); 7.53 (d, J ¼ 8.4, HꢀC(8), HꢀC(12), HꢀC(8’), HꢀC(12’));
7.27 (d, 3J ¼ 8.0, HꢀC(15), HꢀC(17), HꢀC(15’), HꢀC(17’)); 7.10 (d, 3J ¼ 8.3, HꢀC(9), HꢀC(11), HꢀC(9’),
HꢀC(11’)); 2.45 (s, 2 MeC6H4); 2.35 (s, 2 MeC6H4). 13C-NMR (CDCl3)1): 189.70 (ArC¼O); 164.44
(C(2)); 159.12 (C(5)); 144.60, 143.49, 135.57, 129.60, 129.23, 128.54, 126.00, 123.95, 118.25 (arom. C);
21.76, 21.65 (4 MeC6H4). Anal. calc. for C38H28O6 (580.63): C 78.61, H 4.86; found: C 78.79, H 4.75.
(3E)-4-(4-Methoxybenzoyl)-3-[4-(4-methoxybenzoyl)-5-(4-methoxyphenyl)-2-oxofuran-3(2H)-yli-
dene]-5-(4-methoxyphenyl)furan-2(3H)-one (6c): From 1c (0.68 g): 0.30 g (52%) of 6c. Dark-violet
crystals. M.p. 3688. IR (ATR): 1749, 1703, 1651 (C¼O), 1259 (CꢀOꢀC). 1H-NMR (CDCl3)1): 7.96 (d, 3J ¼
8.2, HꢀC(14), HꢀC(18), HꢀC(14’), HꢀC(18’)); 7.62 (d, 3J ¼ 8.9, HꢀC(8), HꢀC(12), HꢀC(8’), HꢀC(12’));
6.94 (d, 3J ¼ 8.5, HꢀC(15), HꢀC(17), HꢀC(15’), HꢀC(17’)); 6.79 (d, 3J ¼ 9.0, HꢀC(9), HꢀC(11),
HꢀC(9’), HꢀC(11’)); 3.85 (s, 2 MeO), 3.78 (s, 2 MeO). 13C-NMR (CDCl3)1): 189.34 (ArC¼O); 164.16
(C(2)); 158.44 (C(5)); 132.33, 131.69, 131.47, 130.85, 129.30, 125.62, 119.51, 117.65, 114.79 (arom. C);
55.71, 55.69 (4 MeO). Anal. calc. for C38H28O10 (644.62): C 70.80, H 4.38; found: C 70.77, H 4.44.
(3E)-4-Benzoyl-3-{4-benzoyl-1-[(dimethylamino)carbonyl]-1,2-dihydro-2-oxo-5-phenyl-3H-pyrrol-
3-ylidene}-2,3-dihydro-N,N-dimethyl-2-oxo-5-phenyl-1-pyrrole-1-carboxamide (8a): From 7a (0.70 g):
0.23 g (36%) of 8a. Dark-blue crystals. M.p. 3078. IR (ATR): 1690, 1665 (C¼O), 1609. 1H-NMR
(CDCl3): 7.60 – 6.94 (m, 20 arom. H); 3.80 (s, 1 Me2N); 3.62 (s, 1 Me2N). 13C-NMR (CDCl3)1): 189.18
(ArC¼O); 175.14 (C(5)); 162.20 (C(2)); 153.01 (NCON); 142.00, 132.87, 132.76, 129.70, 129.01, 128.78,

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128.29 (arom. C); 114.04, 113.89 (C(4), C(4’)); 40.71 (MeN); 38.96 (MeN). Anal. calc. for C40H32N4O6
(664.71): C 72.28, H 4.85, N 8.43; found: C 71.97, H 4.93, N 8.38.
(3E)-4-Benzoyl-3-{4-benzoyl-1-[(diethylamino)carbonyl]-1,2-dihydro-2-oxo-5-phenyl-3H-pyrrol-3-
ylidene}-N,N-diethyl-2,3-dihydro-2-oxo-5-phenyl-1H-pyrrole-1-carboxamide (8b): From 7b (0.75 g):
1
0.22 g (32%) of 8b. Dark-blue crystals. M.p. 3158. IR (ATR): 1699, 1670 (C¼O). H-NMR (CDCl3):
7.80 – 6.95 (m, 20 arom. H); 3.30 (q, 3J ¼ 7.0, 2 H, CH2N); 3.15 (q, 3J ¼ 7.1, 2 H, CH2N); 3.05 (q, 3J ¼ 6.9,
3
3
4 H, CH2N); 0.94 (t, J ¼ 7.1, Me); 0.88 (t, 3J ¼ 7.2, Me); 0.81 (t, J ¼ 7.0, 2 Me). 13C-NMR (CDCl3)1):
189.20 (ArC¼O); 175.77 (C(5)); 165.90 (C(2)); 154.44 (NCON); 142.07, 131.76, 131.99, 130.31, 129.12,
128.82, 127.89, 127.45 (arom. C); 114.76, 114.09 (C(4), C(4’)); 42.82 (CH2N); 42.00 (CH2N); 12.98 (Me);
12.65 (Me). Anal. calc. for C44H40N4O6 (720.81): C 73.32, H 5.59, N 7.77; found: C 73.45, H 5.45, N 7.82.
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Received August 23, 2010