294 Tripathi
Asian J. Chem.
that the primary hydroxyl groups are located at the more restric-
ted rim of the cylinder. The cyclodextrins are known to catalyze
reactions by supramolecular catalysis involving reversible
formation of host–guest complexes by non-covalent bonding
as seen in enzymes [19,20]. Cyclodextrins bind substrates by
molecular recognition and catalyze reactions in a selective
manner. These particular properties of cyclodextrin make them
a good choice in supramolecuar catalysis. Molecular recogni-
tion depends on the size, shape and hydrophobicity of the guest
molecule. The biochemical selectivity in supramolecular
catalysis allows only certain regions of molecule for favourable
attack, is superior to chemical selectivity where attack is due
to intrinsic activity of substrate [21]. Cyclodextrin once used
can be recovered after completion of reaction. Previously, an
improved synthesis of various tryptanthrin derivatives can be
achieved with β-cyclodextrins catalysis in water is also reported
[22].
Motivated by these facts and keeping our goal to develop
a new catalytic system to reveal the catalytic potential of
β-cyclodextrins, here we plan our strategy to use β-cyclodextrin,
a cyclic carbohydrate and water soluble catalyst for multicom-
ponent reaction to synthesize spirooxindole derivatives.
Cyclodextrins are proved to be a remarkable catalyst in many
of the oxidation reactions [23-25]. However at best of our predic-
tion the area of multicomponent synthesis is almost untouched
by using cyclodextrin as a catalyst, as only few spiro heterocyclic
structure have been generated using MCRs.
was extracted by ethyl acetate and evaporated under reduced
pressure. Solid residue was further crystallized by methanol
and filtrate was kept for catalyst recovery.
In order to develop a green catalyst for multicomponent
reaction we planned our strategy of utilizing cyclodextrin as
a catalyst, for synthesis of oxindole nucleus. The three most
common cyclodextrins are α, β and γ-species having 6, 7 and
8 sugar molecules respectively in the ring system [20]. During
the course of the screening of the type and amount of the
catalyst among all the three forms α, β and γ-cyclodextrins
were screened. For optimization of the catalyst, the reaction
of isatoic anhydride (1), isatin (2) and aniline (3) was taken as
the model reaction. After screening of all the three forms of
cyclodextrin very good result was obtained by using β-cyclo-
dextrin as a catalyst, whereas products were formed in very
low yield by using α-cyclodextrin and γ-cyclodextrin (Table-1).
No product formation was detected without using cyclodextrin,
it showed that cyclodextrin plays an essential role in catalyzing
the reaction. The enhanced activity of β-CD may be attributed
by its lowest water solubility among all of the CDs and appro-
priate size of its cavity. Due to low solubility its hydroxyl group
is more available for the formation of host-guest complex
[24,25]. Hence, β-cyclodextrin was selected as catalyst for the
reaction.
TABLE-1
SUMMARY OF DIFFERENT CATALYST USED
Entry
1
2
3
4b
Catalyst
Solvent
Water
Water
Water
Time (h)
Yielda (%)
EXPERIMENTAL
13
3
11
–
21
89
19
–
α-CD
β-CD
γ-CD
–
All the reactions were carried out at room temperature
that is 28-32 °C, unless otherwise specified. All the reagents
were purchased from Sigma-Aldrich Chemical Co, Lancaster
and were used directly without any further purification. NMR
spectra were obtained using the Brucker DRX 200 and 300
MHz spectrometer. Chemical shifts (δ) are given in ppm rela-
tive to TMS, coupling constants (J) in Hz. IR spectra were taken
on VARIAN FT-IR spectrometer as KBr pellets (when solid).
Elemental analysis was performed using a Perkin ElmerAuto-
system XL Analyzer. Melting points were measured using a
COMPLAB melting point apparatus. Reactions were moni-
tored by thin-layer chromatography (TLC) carried out on 0.25
mm silica gel plates visualized with UV light.
General procedure for synthesis of compound (4a-r):
β-Cyclodextrin (30 mol %), isatoic anhydride (1.0 mol eq.)
and substituted isatin (1.0 mol eq.), were mixed in 8 mL water
followed by stirring for 0.5 h at room temperature. Then
primary amine (1.0 mol eq.) was added and reaction mixture
was stirred vigorously upto disappearance of reactants on TLC
(monitored by silica TLC).After completion reaction mixture
Water
b
a% yield of purified fractions, reaction was done in absence of any
catalyst.
Multicomponent synthesis of spiroindole quinazoline
derivatives: Subsequently to verify the general procedure of
reaction, various types of isatin derivatives and substituted
primary amines were tested under the optimized reaction
conditions (Scheme-I), the results are summarized in Table-2.
Reaction was carried out by dissolving cyclodextrin in
water, followed by addition of isatoic anhydride, amine and
isatin. Reaction mixture was stirred vigorously at room tempe-
rature to give the desired product in high yield. Reaction goes
smoothly without the formation of any side products. The
reaction was carried out for appropriate time duration at room
temperature. Further in order to incorporate substrate variation
to support our developed protocol, we used differently substi-
tuted benzaldehydes in place of isatin for above multicom-
ponent reaction in same reaction condition (Scheme-II). It is
O
O
R1
O
β-cyclodextrin
R3
R1
N
O
Water
NH2
O
R3
Stirring
room temperature
N
R2
3
N
H
O
N
O
H
N
R2
1
2
4(a-r)
Scheme-I: Synthesis of different spiroindole quinazolines derivatives
Tripathi, Vishwa Deepak
