One-pot, three-component synthesis of a library of spirooxindole- pyrimidines catalyzed by magnetic nanoparticle supported dodecyl benzenesulfonic acid in aqueous media

Article abstract of DOI:10.1021/co3000264

Dodecyl benzenesulfonic acid functionalized silica-coated magnetic nanoparticles (γ-Fe₂O₃@SiO₂-DDBSA) were readily prepared and identified as an efficient catalyst for the synthesis of a library of spirooxindole-pyrimidine

Full text of DOI:10.1021/co3000264

Research Article
pubs.acs.org/acscombsci
One-Pot, Three-Component Synthesis of a Library of Spirooxindole-
Pyrimidines Catalyzed by Magnetic Nanoparticle Supported Dodecyl
Benzenesulfonic Acid in Aqueous Media
†
†
†
,†
,‡
Jia Deng, Li-Ping Mo, Fei-Yang Zhao, Zhan-Hui Zhang,* and Shou-Xin Liu*
†Key Laboratory of Inorganic Nanomaterial of Hebei Province, College of Chemistry & Material Science, Hebei Normal University,
Shijiazhuang 050024, China
‡
State Key Laboratory Breeding Base-Hebei Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science &
Technology, Shijiazhuang, 050018, China
*
S Supporting Information
ABSTRACT: Dodecyl benzenesulfonic acid functionalized silica-coated magnetic nanoparticles (γ-Fe O @SiO -DDBSA) were
2
3
2
readily prepared and identified as an efficient catalyst for the synthesis of a library of spirooxindole-pyrimidine derivatives by
three-component condensation reaction of barbituric acids, isatins and cyclohexane-1,3-diones. The aqueous reaction medium,
easy recovery of the catalyst using an external magnet, and high yields make the protocol sustainable and economic.
KEYWORDS: one-pot synthesis, three-component reaction, spirooxindole-pyrimidine derivatives,
functionalized silica-coated magnetic nanoparticles
INTRODUCTION
We have recently reported that magnetic Fe O nanoparticles
3 4
■
8
are excellent catalysts for the synthesis of quinoxalines and 2,3-
Currently, the development of new strategies for the recycling
of catalysts has become an important research field for reasons
of economic and environmental impact. Although catalysts
immobilized on heterogeneous supports such as polystyrene
and inorganic materials allow for recycling through filtration or
centrifugation inevitably leads to the loss of the catalyst in the
separation processes. To further address the issues of
recyclability and reusability, magnetic nanoparticles (MNPs)
have emerged as an attractive catalyst support because of their
ability to be separated by magnetic fields. Moreover, magnetic
nanoparticles have high surface area, low toxicity and price,
remarkable chemical and mechanical stability. The surface of
MNPs can be functionalized easily through appropriate surface
modifications to enable the loading of a variety of desirable
functionalities. Recently, MNPs have been successfully utilized
to immobilize enzymes, transition metal catalysts and organo-
9
dihydroquinazolin-4(1H)-ones. We have developed an effi-
cient method for one-pot reductive amination of carbonyl
compounds using NaBH in the presence of a magnetically
4
10
recoverable γ-Fe O @HAP-SO H. Immobilization of TfOH
2
3
3
onto the silica-coated magnetic nanoparticles has also been
11
successfully achieved. In continuation with our interest in
developing efficient and environmental benign synthetic
12
methodologies, we have prepared a new type of immobilized
dodecyl benzenesulfonic acid (DDBSA) catalyst using magnetic
nanoparticles (γ-Fe O @SiO -DDBSA) and found that it is a
2
3
2
highly active and recyclable catalyst for the synthesis of
spirooxindole-pyrimidine derivatives by the three-component
condensation reaction of cyclohexane-1,3-diones, barbituric
acids and isatins or acenaphthylene-1,2-dione in refluxing water
(
Scheme 1).
1
−5
catalysts.
Meanwhile, multicomponent reactions (MCRs)
RESULTS AND DISCUSSION
The MNP-supported DDBSA catalyst was prepared according
to the procedure shown in Scheme 2. Coating of a layer of silica
have the great advantage of eliminating the isolation of unstable
intermediates, and reducing the number of discrete chemical
steps and waste products. On the other hand, spirooxindoles
and pyrimidines are ubiquitous heterocyclic structural motifs
present in a large number of natural and synthetic molecules
with a wide range of utilities in medicinal chemistry. Thus,
■
6
on the surface of γ-Fe O nanoparticles was achieved by
2
3
sonication of γ-Fe O suspension in an alkaline ethanol−water
2
3
7
design of a recyclable catalytic system that promotes efficient
one-pot synthesis of spirooxindole-pyrimidine derivatives is still
strongly desirable.
Received: March 5, 2012
Revised: April 21, 2012
Published: April 25, 2012
©
2012 American Chemical Society
335
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341

ACS Combinatorial Science
Research Article
Scheme 1. Synthesis of 8,9-Dihydrospiro[chromeno[2,3-d]pyrimidine-5,3′-indoline] and Spiro[acenaphthylene-1,5′-
chromeno[2,3-d]pyrimidine] Derivatives
Scheme 2. Synthesis of γ-Fe O @SiO -DDBSA
Table 1. Influence of Different Catalysts on the Reaction of
,5-Dimethylcyclohexane-1,3-dione, Barbituric Acid, and
Isatin
2
3
2
5
a
solution of tetraethyl orthosilicate (TEOS). Then, DDBSA was
added to a suspension of γ-Fe O @SiO in methanol, while
2
3
2
dispersed by sonication. The mixture was concentrated and the
residue was heated at 110 °C for 2 h under vacuum to obtain
DDBSA-functionalized silica-coated magnetic nanoparticles [γ-
Fe O @SiO -DDBSA] (Scheme 2). The loading of DDBSA
moiety on surface was determined by means of back-titration
and pH analysis (0.25 mmol/g, 10 mg = 0.0025 mmol of
DDBSA). The energy dispersive spectrum (EDS) indicated the
presence of Fe, S, Si, O, and C. Scanning electron microscopy
b
entry
catalyst (15 mol %)
time (h)
yield (%)
1
no
10
10
10
10
10
10
10
10
10
10
10
10
10
10
3
trace
15
2
3
2
2
acetic acid
3
trifluoromethanesulfonic acid
silicotungstic acid
25
4
51
5
HClO /SiO2
40
4
6
LiCl
13
(
SEM) revealed that the catalyst presented the uniform size of
7
cerium ammonium nitrate
28
nanoparticles with average diameter around 50 nm. Trans-
mission electron microscopy (TEM) further confirmed this
catalyst was encapsulated by a thin silica layer. FT-IR spectra of
γ-Fe O @SiO -DDBSA displayed peaks that are characteristic
8
nano Fe O4
trace
trace
trace
30
3
9
nano γ-Fe O3
2
10
11
12
13
14
nano γ-Fe O @SiO
2
2
3
nano γ-Fe O @SiO −HClO
4
2
3
2
2
3
2
of functionalized DDBSA group, which clearly differs from that
of the unfunctionalized silica-coated nanomagents (γ-Fe O @
nano γ-Fe O @SiO −HBF
20
2
3
2
4
nano γ-Fe O @HAP-SO H
25
2
3
2
3
3
1
3
SiO2). The magnetic core was analyzed by XRD and the
observed diffraction pattern agrees well with the JCPDS
database for magnetite (see the Supporting Information,
Figures 1−3).
The activity of the prepared catalyst as described above was
next tested in the model reaction of 5,5-dimethylcyclohexane-
nano γ-Fe O @SiO −H PW O
12 40
35
2
3
2
3
15
nano γ-Fe O @SiO -DDBSA
95
2
3
2
a
Experimental conditions: 5,5-dimethyl-cyclohexane-dione (1 mmol),
barbituric acid (1 mmol), isatin (1 mmol), catalyst (15 mmol %), and
b
H O (5 mL). Isolated yields.
2
1
,3-dione 1{1}, barbituric acid 2 {1}, and isatin 3 {1} in
the results showed that 15 mol % of catalyst was the best choice
for the completing the reaction. At a lower catalyst loading the
reaction took longer and was not completed.
refluxing water. The reaction occurred smoothly in the
presence of 15 mol % of γ-Fe O @SiO -DDBSA, affording a
2
3
2
single product in 95% yield (Table 1, entry 15). Although γ-
With the optimal conditions, we embarked on an
investigation of the substrate scope of this new multi-
component domino process with two cyclohexane-1,3-diones,
three barbituric acids, and ten isatins (Figure 1 and Scheme 1).
The results are summarized in Table 3. Various isatins reacted
efficiently with dimedone and barbituric acids to afford the
desired 8,9-dihydrospiro[chromeno[2,3-d]pyrimidine-5,3′-indo-
line]-2,2′,4,6(1H,3H,7H)-tetraones (4) in high yields (Table 3,
entries 1−16). Variation of the electronic properties of the
substituents at either C5 of isatins was tolerable with high yields
ranging from 88% to 95%. Furthermore, the nitrogen protected
isatin substrates were suitable for the reaction, but no reaction
was observed with more sterically demanding substrates, such
as 4-bromoistain. When malonyl urea was replaced by
thiobarbituric acid, 2-thioxo-2,3,8,9-tetrahydrospiro[chromeno-
Fe O @HAP-SO H is well-known to be a good catalyst for
2
3
3
1
0,14
some organic reactions,
its catalytic activity for this reaction
was lower than γ-Fe O @SiO -DDBSA (Table 1, entry 13).
2
3
2
Other catalysts including acetic acid, trifluoromethanesulfonic
acid, silicotungstic acid, HClO /SiO , LiCl and cerium
4
2
ammonium nitrate were less effective (Table 1, entries 2−7).
Notably, only a trace amount of the target product was
observed when the reaction was performed in the absence of
the catalyst (Table 1, entry 1).
The efficiency of the supported catalyst was found to be
affected by the nature of the solvent and the quantity of the
catalyst used in the reaction. After solvent screening, water
proved to be the best choice for this transformation. The
reaction was also monitored with different catalyst loading and
3
36
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341

ACS Combinatorial Science
Research Article
a
Table 2. Optimization of Reaction Conditions
examined substrates gave the corresponding spiro-
[
acenaphthylene-1,5′-chromeno[2,3-d]pyrimidine] derivatives
catalyst loading
(mol %)
temperature
time
yield
b
(6) in high yields under the same reaction conditions.
Unfortunately, although we screened a lot of conditions,
acyclic 1,3-diones such as acetylacetone and dibenzoylmethane
failed to give the desired spirooxindole-pyrimidines.
entry
solvent
CH Cl
(°C)
(h)
(%)
1
2
3
4
5
6
7
8
9
15
15
15
15
15
15
15
15
5
reflux
reflux
reflux
reflux
reflux
reflux
reflux
100
10
10
10
10
10
10
10
10
6
20
30
32
40
51
35
20
36
70
83
95
95
2
2
THF
CH CN
3
The structures of the prepared 8,9-dihydrospiro[chromeno-
2,3-d]pyrimidine-5,3′-indoline]-2,2′,4,6(1H,3H,7H)-tetraones
4) and spiro[acenaphthylene-1,5′-chromeno[2,3-d] pyrimi-
MeOH
EtOH
[
(
DMF
dine] derivatives (6) were characterized by spectroscopic
methods. In cases of compounds 4 and 6, the products were
obtained as 1:1 mixtures of diastereomers. In addition, the
structure of product 4{2,2,5} was further confirmed by single
crystal X-ray (see the Supporting Information, Figure 4).
Although the exact mechanism for this three-component
reaction has not been established at present, a plausible
mechanism for the formation of 8,9-dihydrospiro[chromeno-
[2,3-d]pyrimidine-5,3′-indoline] derivatives (4) (Scheme 3) is
presented on the basis of the analysis of similar multi-
Toluene
DMSO
H O
2
reflux
reflux
reflux
reflux
1
1
1
0
1
2
10
15
20
H O
2
4
H O
2
3
H O
2
3
a
Experimental conditions: 5,5-dimethyl-cyclohexane-dione (1 mmol),
barbituric acid (1 mmol), isatin (1 mmol), and solvent (5 mL).
Isolated yields.
b
7
component reaction of istain. First, reaction of dimedone
[
2,3-d]pyrimidine-5,3′-indoline]-2′,4,6(1H,7H)triones were also
1{1} with isatin 3{1} to yield intermediate I, which reacted
further with barbituric acid 2{1} to form intermediate III,
followed by cyclization to afford 4{1,1,1} and water.
Alternatively, the intermediate III may be produced by addition
of dimedone 1{1} to intermedite II derived from the reaction
between isatin 3{1} and barbituric acid 2{1}. Attempts to
isolate intermediate I and II did not successful due to they are
too reactive. The intermediate I was quickly converted into
3′,3′,6′,6′-tetramethyl-3′,4′,6′,7′-tetrahydrospiro[indoline-3,9′-
obtained in high yields (Table 3, entries 29−40). In addition,
the model reaction was carried out in a scale of 50 mmol. As
expected, the reaction proceeded nicely to afford the desired
product in 92% yield in 3.5 h.
To further expand the potential of this approach as a tool for
the construction of spirooxindole-pyrimidines, we investigated
the reaction of acenaphthylene-1,2-dione (5), barbituric acids,
and cyclohexane-1,3-diones. As shown in Table 3, all the
Figure 1. Diversity of reagents.
3
37
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341

ACS Combinatorial Science
Research Article
Table 3. One-Pot Synthesis of 8,9-
hexanedione, barbituric acid and isatine. After each run, THF
was added to dissolve the product, and the catalyst was
separated by attaching an external magnet onto the reaction
vessel. After a simple wash by THF and subsequent vacuum
removal of residual solvent, the catalyst was reused for next run.
To our delight, the catalyst was highly reusable under the
investigated conditions, preserving almost unaltered its initial
catalytic activity after six uses (see the Supporting Information,
Figure 5). No quantifiable amount of leached Fe was detected
in the filtrates as determined by inductively coupled plasma
atomic emission spectroscopy (ICP-AES). Furthermore, the
TEM images of the catalyst after six recycles did not show any
significant change in the shape and size of catalyst particles,
proving its robustness.
Dihydrospiro[chromeno[2,3-d]pyrimidine-5,3′-indoline]
Derivatives 4 and Spiro[acenaphthylene-1,5′-chromeno[2,3-
d]pyrimidine] Derivatives 6
mp (°C)
a
entry
product
time (h) yield (%)
found
>300
reported
7
e
1
2
3
4
5
6
7
8
9
4{1,1,1}
4{1,1,2}
4{1,1,3}
4{1,1,4}
4{1,1,5}
4{1,1,6}
4{1,1,7}
4{1,1,8}
4{1,1,9}
4{1,1,10}
4{1,2,1}
4{1,2,2}
4{1,2,4}
4{1,2,5}
4{1,2,6}
4{1,2,8}
4{2,1,1}
4{2,1,2}
4{2,1,4}
4{2,1,5}
4{2,1,6}
4{2,1,8}
4{2,2,1}
4{2,2,2}
4{2,2,4}
4{2,2,5}
4{2,2,6}
4{2,2,8}
4{1,3,1}
4{1,3,2}
4{1,3,4}
4{1,3,5}
4{1,3,6}
4{1,3,8}
4{2,3,1}
4{2,3,2}
4{2,3,4}
4{2,3,5}
4{2,3,6}
4{2,3,8}
6{1,1,5}
6{1,2,5}
6{1,3,5}
6{2,1,5}
6{2,2,5}
6{2,3,5}
3.0
5.5
6.0
1.0
2.0
2.5
4.0
3.0
3.0
3.0
3.5
3.5
1.5
2.5
3.0
3.5
3.0
6.0
1.0
2.0
2.5
3.5
3.5
5.5
1.5
2.5
3.0
3.5
4.0
6.0
2.0
3.0
3.5
4.0
4.0
6.0
2.0
2.0
3.5
4.0
3.0
3.0
3.5
3.5
3.5
4.0
95
93
92
95
95
94
93
95
93
90
95
94
95
95
95
90
93
88
94
93
93
94
92
85
94
93
93
90
95
94
93
95
93
93
92
88
91
93
93
88
94
91
93
93
91
92
>300
290
7e
292−293
>300
>300
>300
7
7
e
e
>300
>300
>300
>300
>300
7k
250−251
256−257
>300
253−255
258−259
>300
CONCLUSIONS
7k
■
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
7e
In summary, we have developed an efficient one-pot, three-
component reaction of barbituric acids, isatins, and cyclo-
hexane-1,3-diones for the direct construction of a library of
spirooxindole-pyrimidine deverivates catalyzed by nano mag-
netically silica-supported dodecyl benzenesulfonic acid in water.
Product separation and catalyst recycling are easily accom-
plished with the assistance of the external magnet. The catalyst
can be recycled at least six times.
>300
>300
>300
>300
7
7
e
e
250−251
>300
250
>300
>300
>300
>300
EXPERIMENTAL PROCEDURES
■
7k
243−244
>300
242−245
General. All solvents and chemicals were obtained
commercially and were used as received. Sonication was
performed in a KQ-250E ultrasonic clearer with a frequency of
7e
>300
>300
>300
4
0 kHz and a nominal power 250 W. X-ray diffraction analysis
>300
was carried out using a PANalytical X’Pert Pro X-ray
diffractometer. Surface morphology and particle size were
studied using a Hitachi S-4800 SEM instrument. Transmission
electron microscope (TEM) observation was performed using
Hitachi H-7650 microscope at 80 KV. Elemental compositions
were determined with a Hitachi S-4800 scanning electron
microscope equipped with an INCA 350 energy dispersive
spectrometer (SEM-EDS) presenting a 133 eV resolution at 5.9
keV. Melting points were determined using an X-4 apparatus
and are uncorrected. IR spectra were recorded using a Bruker-
TENSOR 27 spectrometer instrument. NMR spectra were
>300
7
7
e
e
288−289
292−293
>300
285
290
>300
>300
>300
7
7
7
e
e
e
282−283
>300
280
>300
>300
>300
>300
1
taken with a Bruker DRX-500 spectrometer at 500 MHz ( H)
>300
13
and 125 MHz ( C) using DMSO-d as the solvent with TMS
6
>300
as internal standard. Elemental analyses were obtained on a
Vario EL III CHNOS elemental analyzer.
7
7
7
e
e
e
>300
>300
>300
>300
Preparation of Dodecyl Benzenesulfonic Acid-Func-
tionalized Silica-Coated Magnetic Nanoparticles. The γ-
Fe O was prepared by a chemical coprecipitation technique of
>300
>300
2
3
291−293
>300
292−294
ferric and ferrous ions in an alkaline solution according to the
17
literature procedures. Coating of a layer of silica on the
>300
surface of the γ-Fe O was achieved by premixing (ultrasonic) a
2
3
>300
dispersion of the purified γ-Fe O nanoparticles (8.5% w/w)
2
3
a
Isolated yield.
with ethanol (80 mL) for 1 h at 40 °C. A concentrated
ammonia solution (1.5 mL) was added and the resulting
mixture stirred at 40 °C for 30 min. Subsequently, tetraethyl
orthosilicate (TEOS, 1.0 mL) was charged to the reaction
vessel and the mixture continuously stirred at 40 °C for 24 h.
The silica-coated NPs were collected using a permanent
magnet, followed by washing three times with ethanol, diethyl
ether, and drying at 100 °C in a vacuum for 24 h.
1
5
xanthene]-1′,2,8′(2′H,5′H)-trione (7) through reaction further
with another molecule of dimedone. The intermediate II was
converted into 5,5′-(2-oxoindoline- 3,3-diyl)bis(pyrimidine-
16
2
,4,6(1H,3H,5H)-trione) (8) with another molecule of
barbituric acid. It is a pity that our results can not distinguish
between these two mechanisms at this time.
The recyclability of magnetic γ-Fe O @SiO -DDBSA was
To a suspension of γ-Fe O @SiO (10.0 g) in 250 mL of dry
2
3
2
2
3
2
examined using the model reaction of 5,5-dimethyl-cyclo-
methanol, dodecyl benzenesulfonic acid (DDBSA, 0.82 g, 2.5
3
38
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341

ACS Combinatorial Science
Research Article
Scheme 3. Proposed Mechanism for the Synthesis of Compound 4{1,1,1}
mmol) was added. The mixture was sonicated for 60 min at
room temperature. The methanol was removed under reduced
pressure and the residue was dried at 110 °C for 2 h to afford γ-
Fe O @SiO -DDBSA (0.25 mmol/g, 10 mg = 0.0025 mmol of
(B2011205031) and the National Basic Research Program of
China (2011CB512007 and 2012CB723501).
Notes
2
3
2
The authors declare no competing financial interest.
DDBSA) as a yellow powder.
Typical Procedure for Synthesis of 8,8-Dimethyl-8,9-
dihydrospiro[chromeno[2,3-d]pyrimidine-5,3′-indo-
line]-2,2′,4,6(1H,3H,7H)-tetraone 4 {1,1,1}. A mixture of
REFERENCES
1) (a) Shylesh, S.; Schu
separable nanocatalysts: Bridges between homogeneous and hetero-
geneous catalysis. Angew. Chem., Int. Ed. 2010, 49, 3428−3459.
b) Polshettiwar, V.; Luque, R.; Fihri, A.; Zhu, H.; Bouhrara, M.;
Basset, J. M. Magnetically recoverable nanocatalysts. Chem. Rev. 2011,
■
(
̈
nemann, V.; Thiel, W. R. Magnetically
5
,5-dimethyl-cyclohexane-dione 1{1} (0.14 g, 1 mmol),
barbituric acid 2{1} (0.13 g, 1 mmol), isatine 3{1} (0.15 g, 1
mmol), and γ-Fe O @SiO -DDBSA (0.6 g) in refluxing water
(
2
3
2
(
5 mL) was stirred for 3 h. The progress of the reaction was
1
11, 3036−3075.
monitored by TLC. After completion of the reaction, γ-Fe O @
2
3
(2) (a) Luque, R.; Baruwati, B.; Varma, R. S. Magnetically separable
SiO -DDBSA could be placed on the side wall of the reaction
2
nanoferrite-anchored glutathione: aqueous homocoupling of arylbor-
onic acids under microwave irradiation. Green Chem. 2010, 12, 1540−
1543. (b) Oliveira, R. L.; Kiyohara, P. K.; Rossi, L. M. High
performance magnetic separation of gold nanoparticles for catalytic
oxidation of alcohols. Green Chem. 2010, 12, 144−149. (c) Polshetti-
war, V.; Varma, R. S. Green chemistry by nano-catalysis. Green Chem.
010, 12, 743−754. (d) Zhang, Q.; Su, H.; Luo, J.; Wei, Y. A magnetic
nanoparticle supported dual acidic ionic liquid: a“quasi-homogeneous”
catalyst for the one-pot synthesis of benzoxanthenes. Green Chem.
vessel with the aid of an external magnet, and water was
removed from the mixture to leave a residue (including the
product and catalyst). Then, the product was dissolved in THF
and the catalyst easily separated from the product by attaching
an external magnet onto the reaction vessel, followed by
decantation of the product solution. This solution was
concentrated to generate the crude product. The crude product
was purified by column chromatography on silica gel using
2
2
012, 14, 201−208. (e) Saha, A.; Leazer, J.; Varma, R. S. O-Allylation
of phenols with allylic acetates in aqueous media using a magnetically
CH Cl /CH OH as the eluent.
2
2
3
separable catalytic system. Green Chem. 2012, 14, 67−71.
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, characterization data of catalyst and
■
(3) (a) Zheng, X.; Zhang, L.; Li, J.; Luo, S. Z.; Cheng, J.-P. Magnetic
nanoparticle supported polyoxometalates (POMs) via non-covalent
interaction: reusable acid catalysts and catalyst supports for chiral
amines. Chem. Commun. 2011, 47, 12325−12327. (b) Wei, Y.; Yang,
R.; Zhang, Y. X.; Wang, L.; Liu, J. H.; Huang, X. J. High adsorptive γ-
AlOOH(boehmite)@SiO /Fe O porous magnetic microspheres for
*
S
product, and the crystal structure of product 4{2,2,5}. Copies of
1
H NMR and 13C NMR spectra of new compounds. This
2
3
4
material is available free of charge via the Internet at http://
pubs.acs.org.
detection of toxic metal ions in drinking water. Chem. Commun. 2011,
7, 11062−11064.
4) (a) Liu, G. H.; Gu, H. Y.; Sun, Y. Q.; Long, J.; Xu, Y. L.; Li, H. X.
4
(
AUTHOR INFORMATION
Corresponding Author
E-mail: zhanhui@mail.nankai.edu.cn (Z.-H. Zhang); chlsx@
63.net (S.-X. Liu).
Magnetically recoverable nanoparticles: highly efficient catalysts for
asymmetric transfer hydrogenation of aromatic ketones in aqueous
medium. Adv. Synth. Catal. 2011, 353, 1317−1324. (b) Arundhathi, R.;
Damodara, D.; Likhar, P. R.; Kantam, M. L.; Saravanan, P.;
Magdaleno, T.; Kwon, S. H. Fe O @mesoporouspolyaniline: a highly
■
*
2
3
4
Funding
efficient and magnetically separable catalyst for cross-coupling of aryl
chlorides and phenols. Adv. Synth. Catal. 2011, 353, 1591−1600.
(c) Firouzabadi, H.; Iranpoor, N.; Gholinejad, M.; Hoseini, J.
Magnetite (Fe O ) nanoparticles-catalyzed Sonogashira−Hagihara
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (21072042, 20872025
and 30873139), Nature Science Foundation of Hebei Province
3
4
3
39
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341

ACS Combinatorial Science
Research Article
reactions in ethylene glycol under ligand-free conditions. Adv. Synth.
Catal. 2011, 353, 125−132. (d) Stein, M.; Wieland, J.; Steurer, P.;
Tolle, F.; Mulhaupt, R.; Breit, B. Iron Nanoparticles supported on
chemically-derived graphene: catalytic hydrogenation with magnetic
catalyst separation. Adv. Synth. Catal. 2011, 353, 523−527. (e) Wu, L.;
removal-cyclisation approach to spirooxindole scaffolds. Org. Biomol.
Chem. 2011, 9, 5104−5108. (b) Chen, H.; Shi, D. Q. Efficient one-pot
synthesis of spiro indoline-3,4′-pyrazolo[3,4-e][1,4]thiazepine dione
via three-component reaction. Tetrahedron 2011, 67, 5686−5692.
(c) Ghahremanzadeh, R.; Fereshtehnejad, F.; Bazgir, A. Chromeno-
[2,3-d]pyrimidine-triones synthesis by a three-component coupling
reaction. Chem. Pharm. Bull. 2010, 58, 516−520. (d) Jadidi, K.;
Ghahremanzadeh, R.; Bazgir, A. Spirooxindoles: reaction of 2,6-
diaminopyrimidin-4(3H)-one and isatins. Tetrahedron 2009, 65,
6
He, Y.-M.; Fan, Q.-H. Controlled reversible anchoring of η -arene/
TsDPEN ruthenium (II) complex onto magnetic nanoparticles: a new
strategy for catalyst separation and recycling. Adv. Synth. Catal. 2011,
3
(
53, 2915−2919.
5) (a) Ye, M. M.; Zhang, Q.; Hu, Y. X.; Ge, J. P.; Lu, Z. D.; He, L.;
2
005−2009. (e) Jadidi, K.; Ghahremanzadeh, R.; Bazgir, A. Efficient
Chen, Z. L.; Yin, Y. D. Magnetically recoverable core-shell nano-
Synthesis of spiro chromeno[2,3-d]pyrimidine-5,3′-indoline-tetraones
by a one-pot and three-component reaction. J. Comb. Chem. 2009, 11,
composites with enhanced photocatalytic activity. Chem.Eur. J.
2
́
010, 16, 6243−6250. (b) Cano, R.; Ramon, D. J.; Yus, M.
3
41−344. (f) Chen, X. H.; Wei, Q.; Luo, S. W.; Xiao, H.; Gong, L. Z.
Impregnated palladium on magnetite, a new catalyst for the ligand-
Organocatalytic synthesis of spiro pyrrolidin-3,3′-oxindoles with high
enantiopurity and structural diversity. J. Am. Chem. Soc. 2009, 131,
free cross-coupling Suzuki-Miyaura reaction. Tetrahedron 2011, 67,
5
́
432−5436. (c) Cano, R.; Yus, M.; Ramon, D. J. Impregnated
1
3819−13825. (g) Galliford, C. V.; Scheidt, K. A. Pyrrolidinyl-
palladium on magnetite as catalyst for multicomponent reductive
spirooxindole natural products as inspirations for the development of
amination reactions and other related reducing processes. Tetrahedron
potential therapeutic agents. Angew. Chem., Int. Ed. 2007, 46, 8748−
2
́
011, 67, 8079−8085. (d) Cano, R.; Ramon, D. J.; Yus, M.
8
758. (h) Zhu, S. L.; Ji, S. J.; Zhang, Y. A simple and clean procedure
Impregnated ruthenium on magnetite as a recyclable catalyst for the
N-alkylation of amines, sulfonamides, sulfinamides, and nitroarenes
using alcohols as electrophiles by a hydrogen autotransfer process. J.
for three-component synthesis of spirooxindoles in aqueous medium.
Tetrahedron 2007, 63, 9365−9372. (i) Kidwai, M.; Jain, A.; Bhardwaj,
S. Magnetic nanoparticles catalyzed synthesis of diverse N-hetero-
cycles. Mol. Diversity 2012, 16, 121−128. (j) Moghaddam, M. M.;
Bazgir, A.; Akhondi, M. M.; Zarnani, A. H.; Ghahremanzadeh, R.
Simple and efficient route to synthesis of functionalized spiro-
́
Org. Chem. 2011, 76, 5547−5557. (e) Cano, R.; Yus, M.; Ramon, D. J.
Impregnated copper or palladium-copper on magnetite as catalysts for
the domino and stepwise Sonogashira-cyclization processes: a
straightforward synthesis of benzo[b]furans and indoles. Tetrahedron
[
chromeno[2,3-d]pyrimidine-3′,5-indoline]-tetraones by K-10 as a
2
(
012, 68, 1393−1400.
reusable catalyst. Org. Chem. J. 2010, 2, 54−59. (k) Moghaddam, M.
M.; Bazgir, A.; Akhondi, M. M.; Ghahremanzadeh, R. Alum
6) (a) De Moliner, F.; Crosignani, S.; Galatini, A.; Riva, R.; Basso, A.
Novel application of α-azido aldehydes in multicomponent reactions:
synthesis of triazolo-fused dihydrooxazinones via a passerini reaction-
dipolar cycloaddition strategy. ACS Comb. Sci. 2011, 13, 453−457.
(
KAl(SO ) •12H O) catalyzed multicomponent transformation:
4
2
2
simple, efficient, and green route to synthesis of functionalized
spiro[chromeno[2,3-d]pyrimidine-5,3′-indoline]-tetraones in ionic
liquid media. Chin. J. Chem. 2012, 30, 709−714.
(
b) Georgescu, E.; Georgescu, F.; Popa, M. M.; Draghici, C.; Tarko,
L.; Dumitrascu, F. Efficient one-pot, three-component synthesis of a
library of pyrrolo [1,2-c]pyrimidine derivatives. ACS Comb. Sci. 2012,
̈
3 4
(8) Lu, H. Y.; Yang, S. H.; Deng, J.; Zhang, Z. H. Magnetic Fe O
nanoparticles as new, efficient, and reusable catalysts for the synthesis
of quinoxalines in water. Aust. J. Chem. 2010, 63, 1290−1296.
14, 101−107. (c) Huang, Z. B.; Hu, Y.; Zhou, Y.; Shi, D. Q. Efficient
one-pot three-component synthesis of fused pyridine derivatives in
ionic liquid. ACS Comb. Sci. 2011, 13, 45−49. (d) Shakibaei, G. I.;
Feiz, A.; Khavasi, H. R.; Soorki, A. A.; Bazgir, A. Simple three-
component method for the synthesis of spiroindeno [1,2-b]pyrido[2,3-
d]pyrimidine-5,3′-indolines. ACS Comb. Sci. 2011, 13, 96−99.
̈
(9) Zhang, Z. H.; Lu, H. Y.; Yang, S. H.; Gao, J. W. Synthesis of 2,3-
dihydroquinazolin-4(1H)-ones by three-component coupling of isatoic
anhydride, amines, and aldehydes catalyzed by magnetic Fe O
3
4
nanoparticles in water. J. Comb. Chem. 2010, 12, 643−646.
10) Deng, J.; Mo, L. P.; Zhao, F. Y.; Hou, L. L.; Yang, L.; Zhang, Z.
H. Sulfonic acid supported on hydroxyapatite-encapsulated-γ-Fe O
(
(
e) Wang, X. S.; Sheng, J.; Lu, L. A.; Yang, K.; Li, Y. L. Combinatorial
2
3
Synthesis of 3-arylideneaminoquinazolin-4(1H)-one derivatives cata-
lyzed by iodine in ionic liquids. ACS Comb. Sci. 2011, 13, 196−199.
nanocrystallites as a magnetically separable catalyst for one-pot
reductive amination of carbonyl compounds. Green Chem. 2011, 13,
(
f) Ye, S. Q.; Wang, H. H.; Wu, J. 1-(Isoquinolin-1-yl)urea library
2
(
576−2584.
generation via three-component reaction of 2-alkynylbenzaldoxime,
11) Liu, Y.-H.; Deng, J.; Gao, J.-W.; Zhang, Z.-H. Triflic acid-
carbodiimide, with electrophile. ACS Comb. Sci. 2011, 13, 120−125.
functionalized silica-coated magnetic nanoparticles as a magnetically
separable catalyst for synthesis of gem-dihydroperoxides. Adv. Synth.
Catal. 2012, 354, 441−447.
(
g) Zhuang, Q. Y.; Wang, X.; Gao, Y. A.; Shi, F.; Jiang, B.; Tu, S. J.
Diversity-oriented synthesis of spiro-substituted 1,3-thiazine library via
a one-pot, two-step, three-component reaction. ACS Comb. Sci. 2011,
(12) (a) Wang, H. J.; Mo, L. P.; Zhang, Z. H. Cerium ammonium
13, 84−88. (h) Sun, J.; Sun, Y.; Xia, E. Y.; Yan, C. G. Synthesis of
nitrate-catalyzed multicomponent reaction for efficient synthesis of
functionalized tetrahydropyridines. ACS Comb. Sci. 2011, 13, 181−
Functionalized 2-aminohydropyridines and 2-pyridinones via domino
reactions of arylamines, methyl propiolate, aromatic aldehydes, and
substituted acetonitriles. ACS Comb. Sci. 2011, 13, 436−441.
1
85. (b) Lu, J.; Guan, Z. Z.; Gao, J. W.; Zhang, Z. H. An improved
procedure for the synthesis of arylboronates by palladium-catalyzed
coupling reaction of aryl halides and bis(pinacolato)diboron in
polyethylene glycol. Appl. Organomet. Chem. 2011, 25, 537−541.
(
i) Teimouri, M. B.; Akbari-Moghaddam, P.; Golbaghi, G. Pseudo-
five-component reaction between 3-formylchromones, meldrum’s acid,
isocyanides and primary arylamines: diversity-oriented synthesis of
novel chromone-containing peptidomimetics. ACS Comb. Sci. 2011,
(c) Zhang, X. N.; Li, Y. X.; Zhang, Z. H. Nickel chloride-catalyzed one-
pot three-component synthesis of pyrazolophthalazinyl spirooxindoles.
Tetrahedron 2011, 67, 7426−7430. (d) Liu, Y. H.; Liu, Q. S.; Zhang, Z.
H. An efficient Friedel-Crafts alkylation of nitrogen heterocycles
catalyzed by antimony trichloride/montmorillonite K-10. Tetrahedron
Lett. 2009, 50, 916−921. (e) Liu, Y. H.; Zhang, Z. H.; Li, T. S. Efficient
conversion of epoxides into β-hydroperoxy alcohols catalyzed by
1
3, 659−666. (j) Zou, Y.; Hu, Y.; Liu, H.; Shi, D. Q. Rapid and
efficient ultrasound-assisted method for the combinatorial synthesis of
spiro indoline-3,4′-pyrano[2,3-c]pyrazole derivatives. ACS Comb. Sci.
2
synthesis of fused 1,4-and 1,2-dihydropyridines by domino reactions of
arylamines, acetylenedicarboxylate, aldehydes, and cyclic 1,3-diketones.
Eur. J. Org. Chem. 2011, 6952−6956. (m) Jiang, H. F.; Li, J. H.; Chen,
Z. W. L-Proline-catalyzed five-component domino reaction leading to
multifunctionalized 1,2,3,4-tetrahydropyridines. Tetrahedron 2010, 66,
012, 14, 38−43. (l) Sun, J.; Sun, Y.; Gao, H.; Yan, C.-G. Selective
antimony trichloride/SiO . Synthesis 2008, 3314−3318. (f) Zhang, Z.
2
H.; Li, J. J.; Li, T. S. Ultrasound-assisted synthesis of pyrroles catalyzed
by zirconium chloride under solvent-free conditions. Ultrason.
Sonochem. 2008, 15, 673−676.
9
(
721−9728.
7) (a) Coote, S. C.; Quenum, S.; Procter, D. J. Exploiting Sm(II)
and Sm(III) in SmI -initiated reaction cascades: application in a tag
(13) Rafiee, E.; Eavani, S. H PW O supported on silica-
3
12 40
encapsulated γ-Fe O nanoparticles: a novel magnetically-recoverable
2
2
3
3
40
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341

ACS Combinatorial Science
Research Article
catalyst for three-component Mannich-type reactions in water. Green
Chem. 2011, 13, 2116−2122.
(
14) Ma’mani, L.; Sheykhan, M.; Heydari, A.; Faraji, M.; Yamini, Y.
Sulfonic acid supported on hydroxyapatite-encapsulated-γ-Fe O3
2
nanocrystallites as a magnetically Brønsted acid for N-formylation of
amines. Appl. Catal. A: Gen. 2010, 377, 64−69.
(
15) Ahadi, S.; Khavasi, H. R.; Bazgir, A. A clean synthesis of
spiro[indoline-3,9-xanthene]trione drivatives. Chem. Pharm. Bull.
008, 56, 1328−1330.
16) Jursic, B. S.; Stevens, E. D. Preparation of dibarbiturates of
2
(
oxindole by condensation of istain and barbituric acid derivatives.
Tetrahedron Lett. 2002, 43, 5681−5683.
(
17) Ma’mani, L.; Heydar, A.; Sheykhan, M. The Ritter reaction
under incredibly green protocol: nano magnetically silica-supported
Brønsted acid catalyst. Appl. Catal. A: Gen. 2010, 384, 122−127.
3
41
dx.doi.org/10.1021/co3000264 | ACS Comb. Sci. 2012, 14, 335−341