New synthesis of the ethyl 2-methyl-4-(2-oxo-2,3-dihydro-1H-3-indolyl)5-phenyl-1H-3-pyrrolecarboxylate
POGREBNOI Vsevolod
Institute of Chemistry, Academy of Sciences of the Republic of Moldova,
Academy str. 3, MD-2028, Chisinau, Republic of Moldova
Reviews: Dr. Stingaci E.P.
Key words: Synthesis, pyrroles, oxindoles, catalyst, ionic liquids.
Pyrroles as well as oxindoles are important heterocyclic scaffolds of medicinal and therapeutically interests
[1-7]. Devising reactions that achieve multi-bond formation in one-step operation is becoming one of the major
challenges for heterocycle and natural product synthesis.
Recently, one-pot procedures have been developed for InCl 3 (20 mol%) catalyzed the synthesis of 2-methyl4-(2-oxo-2,3-dihydro-1H-3-indolyl)-5-phenyl-1H-3-pyrrolecarboxylates [8].
This procedure do not require the isolation of the initial Michael addition product prior to the Paal-Knorr
condensation, but InCl3 are strongly acidic and highly expensive, and so the development of neutral alternatives like
task-specific ionic liquids would extend the scope of this approach.
Ph
H
N
NH 4OAc
O
+
Ph
O
OEt
O
N
H
O
CO2 Et
catal
O
EtOH,
reflux
N
H
Herein, we wish to report the use of metal-ion-containing ionic liquids as promoters for the synthesis of ethyl
2-methyl-4-(2-oxo-2,3-dihydro-1H-3-indolyl)-5-phenyl-1H-3-pyrrolecarboxylate.
At the outset of the study, the synthesized compounds 1, 2 and 4-6 were tested in the selected reaction of
ammonium acetate, ethyl acetoacetate with 3-phenacylideneoxindole in EtOH at 77°C and the results are
summarized in Table 1.
Table 1. Melting Points/or Glass Transition Points (onset temperature, ˚C) and catalyst activity parameters of
investigated ionic liquids (formulas presented without solvent water molecules).
Ionic liquids
*T
[mcmmim]FeCl4 (1)
[Fe3O(cmmim)6(H2O)3](FeCl4)7 (2)
[Fe3O(cmmim)6(MeOH)3](FeCl4)7 (3)
[Fe3O(cmmim)6(H2O)3](FeCl4)3Cl4 (4)
[Fe3O(cmmim)6(H2O)3](Tf2N)7 (5)
[Fe3O(cepy)6(H2O)3](FeCl4)6Cl (6)
*T (glass transition point)a/T
b
g
m.p. (melting point) at heating (˚C);
(˚C)
42b
78a
103a
92b
94a
Yield/time
(%/hours)
86/2
94/2
98/2
98/2
96/2
Compounds 4 and 5 gave the best results (yield 98%) among these tested catalysts (Table 1). By optimizing
the reaction conditions, it was found that ~0.313 mol% of 1 was enough for the completion of the reaction with good
yield. Another aim of our study was to investigate the recycling of catalysts. It is worth noting that the catalysts can
be reused at least ten times without significant loss of activity for 4-6 and a maximum of five times for 1 and 2.
References
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