Meglumine: A novel and efficient catalyst for one-pot, three-component combinatorial synthesis of functionalized 2-amino-4 H-pyrans

Article abstract of DOI:10.1021/co400107j

An efficient one-pot synthesis of functionalized 2-amino-4H-pyrans by a meglumine-catalyzed three-component reaction has been developed. A broad range of substrates including aromatic and heteroaromatic aldehydes, isatin derivatives, and acenaphthenequino

Full text of DOI:10.1021/co400107j

Technology Note
pubs.acs.org/acscombsci
Meglumine: A Novel and Efficient Catalyst for One-Pot,
Three-Component Combinatorial Synthesis of Functionalized
2‑Amino‑4H‑pyrans
Rui-Yun Guo, Zhi-Min An, Li-Ping Mo, Rui-Zhi Wang, Hong-Xia Liu, Shu-Xia Wang,
and Zhan-Hui Zhang*
College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050024, China
S
* Supporting Information
ABSTRACT: An efficient one-pot synthesis of functionalized 2-amino-
4H-pyrans by a meglumine-catalyzed three-component reaction has
been developed. A broad range of substrates including aromatic and
heteroaromatic aldehydes, isatin derivatives, and acenaphthenequinone
are condensed with enolizable C−H activated compounds and
alkylmalonates to give the desired products in high to excellent yields.
This methodology provides an alternative approach for rapid access to
construct a diversity-oriented library of 4H-pyrans.
KEYWORDS: one-pot synthesis, three-component reaction, functionalized 2-amino-4H-pyrans, meglumine
methodology for the preparation of these heterocyclic
compounds is highly desirable.
yran and its derivatives are an important class of hetero-
Pcyclic compounds, which constitute the key core of various
natural products1 as well as photochromic materials.2 They
exhibit a wide range of biological activities such as anticancer,3
antimicrobial,4 antioxidant,5 and antiproliferative properties.6
4H-Pyran derivatives are also potential calcium channel
antagonists, which are structurally similar to biologically active
1,4-dihydropyridines.7 In addition, amino-4H-pyrans are often
used in cosmetics and pigments, or are utilized as poten-
tially biodegradable agrochemicals. The 4H-pyran derivatives
bearing a nitrile functionality are also useful intermediates
for the synthesis of various compounds such as pyridones, 1,4-
dihydropyridines, lactones, pyranopyrazoles, imidoesters, and
aminopyrimidines.8 Because of the important aforementioned
properties of pyran derivatives, preparation of this heterocyclic
nucleus has gained great importance in organic synthesis.9 The
most straightforward synthesis of this heterocyclic system
involves a three-component coupling of an aldehyde with alkyl-
malonates and diverse enolizable C−H activated acidic com-
pounds in the presence of homogeneous or heterogeneous
catalysts such as diammonium hydrogen phosphate,10 N-methyl-
imidazole,11 4-(dimethylamino)pyridine (DMAP),12 lithium
bromide,13 hexamethylenetetramine,14 1,8-diazabicyclo[5.4.0]-
undec-7-ene (DBU),15 potassium phthalimide-N-oxyl,16 li-
pase,17 Ce(SO4)2·4H2O,18 cerium(III) chloride,19 tetrabutyl-
ammonium fluoride (TBAF),20 or a basic ionic liquid.21 This
reaction proceeds in glycerol22 or choline chloride-urea.23 With
widespread applications and bioactivity, the development of
efficient, economically and environmentally benign synthetic
Following the increasing environmental and economic
considerations, the search for enviro-economic synthetic
methods for organic reactions has received overwhelming
attention. In this regard, efforts are being made to replace the
expensive and hazardous catalysts with biodegradable materials,
which are safe, inexpensive, harmless, and environmentally
benign. Recently, Gu et al. introduced meglumine and gluconic
acid aqueous solution as a promoting medium and catalyst for
the multicomponent reaction of β-ketosulfones and form-
aldehyde.24 Meglumine is an amino sugar derived from sorbitol
with molecular formula C7H17NO5 (Figure 1). In particular, the
Figure 1. Structure of meglumine.
low toxicity of meglumine allows its use in the formulation of
pharmaceuticals as an excipient and in conjunction with
iodinated compounds in contrast media such as diatrizoate
meglumine and iodipamide meglumine.25 Meglumine possesses
environmentally benign properties such as biodegradability and
physiological inertness. Additionally, meglumine is inexpensive,
Received: August 15, 2013
Revised: September 18, 2013
Published: October 18, 2013
© 2013 American Chemical Society
557
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563

ACS Combinatorial Science
Technology Note
noncorrosive, stable to air and moisture, and readily available in
the market. It contains an amino group, primary and secondary
hydroxyl groups that can activate the nucleophilic as well as
electrophilic components of the reactions by hydrogen bonding
and donation of a lone pair of electrons, respectively. Multi-
component coupling reactions (MCRs) have been acknowl-
edged as powerful and bond-forming efficient tools for the
construction of novel and structurally complex molecules with a
minimum of reaction steps and simple workup procedures.
Thus, the combination of MCRs, a biodegradable catalyst, and
a green solvent will make the chemical reaction more envi-
ronmentally as well as economically viable.26
Considering the above subjects and continuing our efforts on
the development of new MCRs and environmental benign
synthetic methodologies,27 we wish to report a facile, one-pot,
three-component process for the synthesis of functionalized
2-amino-4H-pyrans from the reaction of aldehydes, isatin deriv-
atives, or acenaphthenequinone with enolizable C−H activated
compounds and alkylmalonates in the presence of meglumine
at room temperature (Scheme 1).
Table 1. Influence of Different Catalysts on the Reaction
of Benzaldehyde, 5,5-Dimethylcyclohexane-1,3-dione, and
a
Malononitrile
b
entry
catalyst
time (min)
yield (%)
1
no
60
60
60
60
60
60
60
60
60
60
60
60
5
40
55
45
50
65
60
50
50
45
40
45
40
97
2
K2CO3
CH3COONa
3
4
CH3COONH4
sodium dodecylbenzenesulfonate
triethylamine
tetrabutylammonium bromide
L-proline
5
6
7
8
9
CuO
10
11
12
13
CeO2
nano ZnO
nano MgO
Scheme 1. Synthesis of Functionalized 2-amino-4H-pyrans
Catalyzed by Meglumine
meglumine
a
Experimental conditions: benzaldehyde (1 mmol), 5,5-dimethylcy-
clohexane-1,3-dione, (1 mmol), malononitrile (1 mmol), catalyst
b
(5 mol %), EtOH-H2O (1:1, 2 mL), room temperature. Isolated yields.
a
Table 2. Optimization of Reaction Conditions
catalyst loading
(mol %)
time
(min)
b
entry
solvent
yield (%)
1
5
5
5
5
5
5
5
5
1
3
5
5
no
10
20
10
60
60
5
93
80
95
70
30
97
95
93
88
92
96
2
MeOH
3
EtOH
4
PEG 400
5
H2O
6
EtOH-H2O (1:1)
EtOH-H2O (2:1)
EtOH-H2O (1:2)
EtOH-H2O (1:1)
EtOH-H2O (1:1)
EtOH-H2O (1:1)
EtOH-H2O (1:1)
7
10
10
5
8
To explore the generality and feasibility of meglumine catalyzed
MCRs, we investigated the optimization of the reaction
conditions using benzaldehyde, 5,5-dimethylcyclohexane-1,3-
dione, and malononitrile as model reactants. Various catalysts
were examined, and the results are summarized in Table 1. To
justify the significance of catalyst in this three-component pro-
cess, the reaction was first performed in the absence of the
catalyst wherein only 40% yield of the target product was
observed even at prolonged reaction time (Table 1, entry 1). In
the presence of potassium carbonate, sodium acetate, or ammo-
nium acetate, the reaction gave 55%, 45%, and 50% isolated
yield of product after 1 h, respectively. In addition, sodium
dodecylbenzenesulfonate, triethylamine, tetrabutylammonium
bromide, and L-proline could also catalyze this transformation,
but no improvement was observed (Table 1, entries 5−8). The
reaction was then performed in the presence of metal oxides
such as CuO, CeO2, ZnO, and MgO (Table 1, entries 9−12).
However, these catalysts were less effective. We then tested the
reaction in the presence of meglumine. Meglumine was found
to be the best catalyst for this process, and the desired product
6{1,1,1}was formed in 97% yield in just 5 min (Table 1, entry
13). We think that in addition to the amino group, the presence
of multiple hydroxyl groups in the structure of meglumine plays
an important role for the formation of product because of the
stabilization of the corresponding intermediates and transition
states by hydrogen bonding.
9
10
5
c
11
5
d
12
5
96, 95, 93
a
Experimental conditions: benzaldehyde (1 mmol), 5,5-dimethylcyclo-
hexane-1,3-dione (1 mmol), malononitrile (1 mmol), solvent (2 mL),
b
c
room temperature. Isolated yields. The reaction was carried out in
50 mmol scale. Catalyst was reused three times.
d
Next, we screened the effect of the solvent and catalyst
loading (Table 2). The reaction was not satisfactory in water,
possibly because of incomplete homogeneity of the reaction
mixture. Further studies showed that aqueous-ethanol (1:1 v/v)
was the best choice of solvent for this transformation. The
reaction was also carried out using different amounts of the
catalyst, and the results showed that 5 mol % of catalyst was the
best choice for completing the reaction in aqueous-ethanol. By
decreasing the amount of catalyst to 3 mol % relative to
substrate, the yield of product decreased (Table 2, entry 10).
Consequently, the best result was obtained by using 5 mol % of
meglumine as the catalyst and aqueous-ethanol (1:1 v/v) as the
solvent (Table 2, entry 6).
Furthermore, when the reaction was scaled up to 50 mmol,
an excellent result was obtained in the same time (Table 2,
entry 11). For utility in large scale syntheses we demonstrated
558
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563

ACS Combinatorial Science
Technology Note
Figure 2. Diversity of reagents.
the recyclability of meglumine for three consecutive cycles with
almost the same catalytic activity (Table 2, entry 12). After
completion of each reaction, the precipitated product was
filtered and washed with aqueous ethanol. The crude product
was purified by recrystallization from ethanol to afford the
desired product. To recover the catalyst, the filtrate was dried
under reduced pressure and the recovered catalyst was washed
with diethyl ether and reused after drying.
transformation, affording the potentially biologically important
2-amino-4H-pyrans in high yields (Table 3, entries 27−29). To
further demonstrate the scope of the substrates subject to
meglumine catalysis, isatins were used as reactants with 5,5-
dimethylcyclohexane-1,3-dione and malononitrile. Gratifyingly,
it was found that the expected products were obtained in
excellent yields, regardless of the effect of substitution on the
isatins (Table 3, entries 30−32). In the case of acenaphthene-
quinone 3{33}, the desired spiro-4H-pyrans 8{33,1,1} was also
produced in 93% yield (Table 3, entry 33). It should be noted
that the reaction with methyl cyanoacetate or ethyl cyano-
acetate required longer reaction times than those with malono-
nitrile, which was probably due to their lower reactivity (Table 3,
entries 34−37).
Subsequently, a variety of enolizable C−H activated com-
pounds such as carbonyl compounds possessing a reactive
α-methylene group cyclohexane-1,3-dione and cyclopentane-
1,3-dione, α-naphthol and β-naphthol, 4-hydroxycoumarin,
and barbituric acids were evaluated in this three-component
reaction. In all cases, the corresponding functionalized
2-amino-4H-pyrans were formed in high to excellent yields.
Furthermore, the reaction may also be extended to acyclic
1,3-dicarbonyl compounds such as acetylacetone, although
longer reaction times were required (Table 3, entries 44−46).
The above results clearly indicate the present catalytic pro-
cedure is extendable to a wide variety of substrates to construct
a diversity-oriented library of 4H-pyrans.
To investigate the scope and limitation of this catalytic
process, 29 aldehydes 1{1−29}, 3 isatins 2{30−32}, acenaph-
thenequinone 3{33}, 3 cyclic ketones 4{1−3}, 1 acyclic 1,3-
dicarbonyl compounds 4{4}, 2 naphthols 4{5−6}, 4-hydroxy-
coumarin 4{7}, 2 barbituric acids 4{8−9}, and 3 acetonitrile
derivatives 5{1−3} were chosen for library validation (Figure 2).
We first examined the reaction of 5,5-dimethylcyclohexane-1,3-
dione 4{1} and malononitrile 5{1} with a diverse array of
aldehydes. As evident from Table 3, this multicomponent
reaction proceeded efficiently, and the desired products were
obtained in high to excellent yields in relatively short times.
The nature of the functional group on the aromatic ring of the
aldehyde exerted a slight influence on the product yield and
reaction time. It was observed that arylaldehydes carrying an
electron-withdrawing group reacted faster with better yield than
those having an electron-donating group. The reaction was also
sensitive to the steric environment of the aromatic aldehyde
with longer reaction times being required for benzaldehydes
containing substituents at the 2-position. Heteroaromatic
aldehydes, such as furan-2-carbaldehyde, thiophene-2-carbalde-
hyde, and pyridine-4-carbaldehyde, readily participated in this
In summary, we have developed a simple and efficient one-pot,
three-component, meglumine catalyzed synthesis of functionalized
559
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563

ACS Combinatorial Science
Technology Note
Table 3. One-Pot Synthesis of 2-Amino-4H-pyran Derivatives
mp (°C)
mp (°C)
time
(min)
yield
a
time
(min)
yield
a
entry
product
(%)
found
reported
entry
product
(%)
found
reported
1
6{1,1,1}
5
97
92
94
95
92
91
93
95
93
93
93
93
93
93
96
95
96
96
94
93
95
96
96
93
96
95
95
92
96
96
93
95
93
91
92
90
91
95
96
93
225−226
200−201
190−191
200−201
209−210
177−178
194−195
224−225
211−212
227−228
241−242
209−210
205−206
215−216
233−234
216−217
235−236
215−216
193−195
229−230
241−242
215−216
185−186
227−228
224−226
218−219
226−227
221−222
153
224−22622
203−20517
188−19018
201−20316
209−21013
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
6{23,2,1}
6{18,3,1}
6{26,3,1}
6{1,4,1}
5
96
95
96
92
93
94
94
94
95
97
95
90
92
93
93
96
93
96
95
95
96
93
95
97
94
97
95
93
95
95
97
93
95
95
94
95
80
90
92
235−236
218−219
178−180
165−166
155−156
169−170
207−208
206−207
245−246
235−236
218−220
255−256
259−60
187−188
254−255
248−249
265−266
208−210
232−233
264−265
263−264
203−204
239−240
>300
235−23613
2
6{2,1,1}
15
13
13
25
20
20
12
12
17
18
14
13
20
7
5
216−21812
3
6{3,1,1}
5
4
6{4,1,1}
150
120
90
15
15
15
10
15
140
120
110
20
15
17
13
30
19
15
20
18
15
15
25
30
35
20
30
25
40
15
20
25
25
30
35
40
16432
15432
17032
5
6{5,1,1}
6{18,4,1}
6{23,4,1}
6{2,5,1}
6
6{6,1,1}
7
6{7,1,1}
195−19620
223−22517
219−22210
226−22819
240−24219
208−20921
204−20510
8
6{8,1,1}
6{9,5,1}
205−20615
243−24412
23635
9
6{9,1,1}
6{18,5,1}
6{23,5,1}
6{25,5,1}
6{9,6,1}
10
11
12
13
16
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
6{10,1,1}
6{11,1,1}
6{12,1,1}
6{13,1,1}
6{14,1,1}
6{15,1,1}
6{16,1,1}
6{17,1,1}
6{18,1,1}
6{19,1,1}
6{20,1,1}
6{21,1,1}
6{22,1,1}
6{23,1,1}
6{24,1,1}
6{25,1,1}
6{26,1,1}
6{27,1,1}
6{28,1,1}
6{29,1,1}
7{30,1,1}
7{31,1,1}
7{32,1,1}
8{33,1,1}
6{18,1,2}
6{23,1,2}
6{18,1,3}
6{23,1,3}
6{9,2,1}
25535
6{16,6,1}
6{23,6,1}
6{9,7,1}
26035
18735
232−23320
215−21611
236−23710
213-21522
192−19510
228−23028
255−25622
247−24914
264−26612
8
6{15,7,1}
6{18,7,1}
6{26,7,1}
6{2,8,1}
5
5
10
5
231−23222
263−26422
262−26322
20333
6{18,8,1}
6{23,8,1}
6{9,9,1}
10
5
213-21710
181−18410
226−22813
5
6{18,9,1}
6{26,9,1}
7{30,2,1}
7{30,3,1}
7{30,5,1}
7{30,6,1}
7{30,7,1}
7{30,8,1}
7{30,9,1}
7{31,5,1}
7{32,5,1}
7{32,9,1}
8{33,2,1}
8{33,3,1}
8{33,7,1}
8{33,8,1}
8{33,9,1}
238−24033
10
5
298−299
>300
297−29822
>30034
5
217−21829
225−22613
222−22322
15
15
14
18
18
10
20
20
18
22
20
10
7
221−222
235−236
>300
220−22222
233−23522
>30022
290−292
278−279
303−304
269−270
170−171
187−188
150−151
180−181
232−233
242−243
202−203
291−29322
277−27822
302−30430
268−27031
17110
298−299
229−230
>300
296−29822
228−22936
>300
225−227
>300
186−18810
>30037
15010
276−277
>300
179−18110
233−23522
241−24312
201−20217
>30031
>30031
>30037
>300
6{18,2,1}
6{22,2,1}
>300
6
a
Isolated yield.
2-amino-4H-pyrans using readily available starting materials.
The salient features of this new methodology are broad
substrate scope, room temperature reaction conditions, short
reaction times, high yields of the products, operational
simplicity, reusability of catalyst and the absence of hazardous
organic solvents, which make it an applicable method for
constructing diverse libraries of 4H-pyrans.
as the solvent with TMS as internal standard. Elemental ana-
lysis was performed by using a Vario EL III CHNOS elemental
analyzer.
Typical Procedure for Synthesis of 2-Amino-7,7-
dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chro-
mene-3-carbonitrile 6 {1,1,1}. A mixture of benzaldehyde
1{1} (0.11 g, 1 mmol)), 5,5-dimethylcyclohexane-1,3-dione
2{1} (0.14 g, 1 mmol), malononitrile 3{1} (0.07 g, 1 mmol),
and meglumine (5 mol %, 0.01g) in EtOH-H2O (1:1, 2 mL)
was stirred at room temperature for 5 min. The progress of the
reaction was monitored by TLC (hexane-EtOAc, 5:1). After
completion of the reaction, the precipitated product was filtered
and washed with aqueous ethanol (5 mL). The crude product
was purified by recrystallization from ethanol to afford the
desired product. To recover the catalyst, the filtrate was dried
under reduced pressure, and recovered catalyst was washed
with diethyl ether (2 mL) twice and reused after drying.
EXPERIMENTAL PROCEDURES
■
General Information. All solvents and chemicals used in
this work were obtained commercially and were used as re-
ceived. Melting points were determined using an X-4 apparatus
and are uncorrected. IR spectra were obtained as potassium
bromide pellets with a Bruker-TENSOR 27 spectrometer. NMR
spectra were recorded with a Bruker DRX-500 spectrometer at
500 MHz (1H) and 125 MHz (13C) using DMSO-d6 or CDCl3
560
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563

ACS Combinatorial Science
Technology Note
Compound 6{6,1,1}. White solid; IR (KBr): 3545, 3327,
3215, 2937, 2193, 1683, 1653, 1606, 1508, 1367, 1251, 1211,
1174, 1035, 842 cm−1; 1H NMR (500 MHz, CDCl3) δ 0.92 (t,
J = 7.0 Hz, 3H, CH3), 1.03 (s, 3H, CH3), 1.10 (s, 3H, CH3),
1.33−1.44 (m, 4H, 2 × CH2), 1.75 (quin, J = 7.0 Hz, 2H,
CH2), 2.19 and 2.24 (AB system, J = 16.5 Hz, 2H, CH2), 2.44
(s, 2H, CH2), 3.90 (t, J = 7.0 Hz, 2H, OCH2), 4.35 (s, 1H,
CH), 4.49 (s, 2H, NH2), 6.80 (d, J = 8.5 Hz, 2H, HAr), 7.13 (d,
J = 8.5 Hz, 2H, HAr) ppm; 13C NMR (125 MHz, CDCl3) δ
14.0, 22.5, 27.6, 28.2, 28.9, 29.0, 32.2, 34.8, 40.7, 50.7, 63.1,
67.9, 114.2, 114.5, 115.6, 119.0, 128.6, 133.6, 135.4, 157.7,
158.2, 161.4, 196.2 ppm; Anal. Calcd for C23H28N2O3: C,
72.60; H, 7.42; N, 7.36. Found: C, 72.42; H, 7.26; N, 7.55.
Compound 6{14,1,1}. White solid; IR (KBr): 3433, 3331,
3219, 2955, 2185, 1687, 1672, 1602, 1518, 1425, 1369, 1344,
7.59 (d, J = 8.0 Hz, 2H, HAr) ppm; 13C NMR (125 MHz,
3
CDCl3) δ 25.0, 33.6, 35.7, 61.4, 117.9, 118.3, 125.7 (q, JFC
=
3.5 Hz), 126.2 (q, 1JFC = 270.6 Hz), 129.9 (q, 2JFC = 32.1 Hz),
144.6, 159.0, 175.3, 200.8 ppm; Anal. Calcd for C16H11F3N2O2:
C, 60.00; H, 3.46; N, 8.75. Found: C, 58.91; H, 3.52; N, 8.93.
Compound 6{2,5,1}. White solid; IR (KBr): 3471, 3396,
3198, 2933, 2185, 1662, 1614, 1573, 1489, 1458, 1377, 1261,
1
1192, 1105, 1022, 756 cm−1; H NMR (500 MHz, CDCl3) δ
3.87 (s, 3H, OCH3), 4.70 (s, 2H, NH2), 5.42 (s, 1H, CH), 6.86
(t, J = 7.5 Hz, 1H, HAr), 6.91 (d, J = 8.0 Hz, 1H, HAr), 7.02
(dd, J = 7.5, 1.5 Hz, 1H, HAr), 7.12 (d, J = 8.5 Hz, 1H, HAr),
7.20 (td, J = 7.5, 1.5 Hz, 1H, HAr), 7.48 (d, J = 8.5 Hz, 1H,
HAr), 7.51 (d, J = 8.5 Hz, 1H, HAr), 7.56 (t, J = 7.5 Hz, 1H,
HAr), 7.78 (d, J = 8.0 Hz, 1H, HAr), 8.16 (d, J = 8.0 Hz, 1H,
HAr) ppm; 13C NMR (125 MHz, CDCl3) δ 34.2, 55.7, 60.7,
111.1, 117.9, 120.0, 120.7, 121.1, 123.2, 124.5, 126.2, 126.5,
127.7, 128.4, 129.6, 132.8, 133.2, 143.6, 156.8, 159.8 ppm; Anal.
Calcd for C21H16N2O2: C, 76.81; H, 4.91; N, 8.53. Found: C,
76.66; H, 5.10; N, 8.38.
1
1253, 1138, 1039, 852 cm−1; H NMR (500 MHz, CDCl3) δ
1.03 (s, 3H, CH3), 1.11(s, 3H, CH3), 2.19 and 2.24 (AB
system, J = 16.5 Hz, 2H, CH2), 2.44 (s, 2H, CH2), 4.37(s, 1H,
CH), 4.50 (s, 2H, NH2), 5.13 (s, 2H, CH2), 6.87 (d, J = 8.5 Hz,
2H, HAr), 7.17 (d, J = 8.5 Hz, 2H, HAr), 7.59 (d, J = 8.5 Hz,
2H, HAr), 8.24 (d, J = 8.5 Hz, 2H, HAr) ppm; 13C NMR (125
MHz, CDCl3) δ 27.9, 28.8, 31.3, 32.2, 34.4, 34.9, 40.7, 50.7,
63.9, 114.2, 118.8, 125.5, 127.0, 140.1, 149.7, 157.5, 161.5,
196.0 ppm; Anal. Calcd for C25H23N3O5: C, 67.41; H, 5.20; N,
9.43. Found: C, 67.22; H, 5.38; N, 9.62.
Compound 6{21,1,1}. White solid; IR (KBr): 3421, 3336,
3217, 2960, 2191, 1700, 1660, 1480, 1430, 1365, 1251, 1211,
1138, 1039, 875 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.05 (s,
3H, CH3), 1.12 (s, 3H, CH3), 2.24 (s, CH2), 2.43 and 2.50 (AB
system, J = 18.0 Hz, 2H, CH2), 4.31 (s, 1H, OH), 4.59 (s, 2H,
NH2), 5.81 (s, 1H, CH), 7.31 (s, 2H, HAr) ppm; 13C NMR
(125 MHz, CDCl3) δ 27.9, 28.8, 31.3, 32.2, 34.4, 34.9, 40.7,
50.7, 63.9, 114.2, 118.8, 125.5, 127.0, 140.1, 149.7, 157.5, 161.5,
196.0 ppm; Anal. Calcd for C18H16Br2N2O3: C, 46.18; H, 3.44;
N, 5.98. Found: C, 45.99; H, 3.60; N, 6.16.
Compound 6{25,5,1}. White solid; IR (KBr): 3473, 3338,
3198, 2935, 2195, 1670, 1602, 1572, 1460, 1408, 1379, 1261,
1
1188, 1114, 1050, 763 cm−1; H NMR (500 MHz, CDCl3) δ
4.81 (s, 2H, NH2), 4.97 (s, 1H, CH), 6.98 (d, J = 8.0 Hz, 1H,
HAr), 7.45−7.54 (m, 5H, HAr), 7.56 (d, J = 8.0 Hz, 1H, HAr),
7.60 (t, J = 8.0 Hz, 1H, HAr), 7.81 (d, J = 8.0 Hz, 1H, HAr),
8.19 (d, J = 8.0 Hz, 1H, HAr) ppm; 13C NMR (125 MHz,
CDCl3) δ 41.4, 60.4, 116.3, 119.5, 120.9, 123.2, 124.0 (q, 1JFC
=
3
3
271.0 Hz),124.4 (q, JFC = 3.8 Hz), 124.8 (q, JFC = 3.8 Hz),
2
125.0, 125.8, 126.9, 127.1, 127.8, 129.4, 131.3 (q, JFC = 32.1
Hz), 131.7, 133.5, 143.4, 145.4, 159.3 ppm; Anal. Calcd for
C21H13F3N2O: C, 68.85; H, 3.58; N, 7.65. Found: C, 69.02; H,
3.75; N, 7.48.
Compound 6{26,7,1}. White solid; IR (KBr): 3325, 3194,
3072, 2877, 2198, 1716, 1602, 1377, 1112, 765 cm−1; 1H NMR
(500 MHz, DMSO-d6) δ 4.60 (s, 1H, CH), 7.47−7.53 (m, 6H,
HAr and NH2), 7.68 (d, J = 8.5 Hz, 2H, HAr), 7.73 (t, J = 7.0 Hz,
1H, HAr), 7.91(d, J = 7.5 Hz, 1H, HAr) ppm; 13C NMR
(125 MHz, DMSO-d6) δ 37.3, 57.6, 103.6, 113.4, 117.1, 119.5,
123.0, 125.2, 125.8 (q, 1JFC = 270.4 Hz), 125.9 (q, 3JFC = 3.8 Hz),
128.3 (q, 2JFC = 31.2 Hz), 129.1, 133.6, 148.4, 152.7, 154.3, 158.5,
160.6 ppm; Anal. Calcd for C20H13F3N2O3: C, 62.18; H, 3.39; N,
7.25. Found: C, 61.99; H, 3.58; N, 7.43.
Compound 6{25,1,1}. White solid; IR (KBr): 3350, 3259,
3176, 2966, 2191, 1683, 1658, 1606, 1469, 1417, 1371, 1330,
1
1219, 1124, 1039, 823 cm−1; H NMR (500 MHz, CDCl3) δ
1.03 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.19 and 2.24 (AB
system, J = 16.5 Hz, 2H, CH2), 2.48 (s, 2H, CH2), 4.47 (s, 1H,
CH), 4.60 (s, 2H, NH2), 7.42 (t, J = 7.5 Hz, 1H, HAr), 7.42 (s,
1H), 7.47 (d, J = 7.5 Hz, 1H, HAr), 7.48 (d, J = 7.5 Hz, 1H,
HAr) ppm; 13C NMR (125 MHz, CDCl3) δ 27.4, 29.0, 32.2,
3
Compound 6{26,9,1}. White solid; IR (KBr): 3441, 3304,
3183, 2193, 1705, 1608, 1323, 1126, 839 cm−1; 1H NMR (500
MHz, DMSO-d6) δ 3.07 (s, 3H, CH3), 3.35 (s, 3H, CH3), 4.45
(s, 1H, CH), 7.44 (s, 2H, NH2), 7.49 (d, J = 8.0 Hz, 2H, HAr),
7.66 (d, J = 8.0 Hz, 2H, HAr) ppm; 13C NMR (125 MHz,
35.6, 40.7, 50.6, 62.9, 113.5, 118.2, 124.1 (q, JFC = 3.75 Hz),
1
2
125.2 (q, JFC = 271.0 Hz), 129.0, 131.1 (q, JFC = 32.0 Hz),
131.4, 144.2, 157.6, 161.9, 195.7 ppm; Anal. Calcd for
C19H17F3N2O2: C, 62.98; H, 4.73; N, 7.73. Found: C, 63.12;
H, 4.90; N, 7.55.
DMSO-d6) δ 28.1, 29.6, 36.9, 58.2, 88.4, 119.3, 125.2 (q, 1JFC
=
Compound 6{29,1,1}. White solid; IR (KBr): 3419, 3394,
3216, 2956, 2187, 1683, 1672, 1600, 1421, 1373, 1251, 1205,
1138, 1037, 854 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.04 (s,
3H, CH3), 1.13 (s, 3H, CH3), 2.21 and 2.27 (AB system, J =
16.5 Hz, 2H, CH2), 2.48 (s, 2H, CH2), 4.40 (s, 1H, CH), 4.69
(s, 2H, NH2), 7.18 (d, J = 6.0 Hz, 2H, HAr), 8.54 (d, J = 6.0 Hz,
2H, HAr) ppm; 13C NMR (125 MHz, CDCl3) δ 27.6, 28.9, 32.3,
35.1, 40.7, 50.5, 61.8, 112.9, 118.1, 122.8, 150.1, 151.6, 157.9,
162.3, 195.6 ppm; Anal. Calcd for C17H17N3O2: C, 69.14; H,
5.80; N, 14.23. Found: C, 68.98; H, 5.96; N, 14.05.
270.2 Hz), 125.7 (q, 3JFC = 3.8 Hz), 127.9 (q, 2JFC = 31.2 Hz),
128.0, 149.3, 150.5, 151.8, 158.2, 160.9 ppm; Anal. Calcd for
C17H13F3N4O3: C, 53.97; H, 3.46; N, 14.81. Found: C, 54.15;
H, 3.62; N, 15.00.
Compound 7{31,5,1}. White solid; IR (KBr): 3483, 3300,
3066, 2966, 2195, 1651, 1597, 1107, 692 cm−1; 1H NMR (500
MHz, DMSO-d6) δ 2.20 (s, 3H, CH3), 6.57 (d, J = 9.0 Hz, 1H,
HAr), 6.88 (d, J = 7.5 Hz, 1H, HAr), 6.90 (s, 1H, HAr), 7.09
(d, J = 7.5 Hz, 1H, HAr), 7.43 (s, 2H, NH2), 7.57 (d, J = 9.0 Hz,
1H, HAr), 7.60 (t, J = 7.5 Hz, 1H, HAr), 7.69 (t, J = 7.5 Hz, 1H,
HAr), 7.90 (d, J = 8.5 Hz,1H, HAr), 8.27 (d, J = 8.5 Hz, 1H,
HAr), 10.6 (s, 1H, NH) ppm; 13C NMR (125 MHz, DMSO-d6)
δ 21.0, 51.4, 55.0, 110.3, 115.4, 119.1, 121.2, 123.3, 123.7, 125.0,
125.9, 127.5, 127.8, 128.2, 130.0, 132.2, 133.5, 135.5, 139.8,
Compound 6{26,3,1}. White solid; IR (KBr): 3404, 3333,
3211, 2937, 2193, 1670, 1643, 1597, 1442, 1375, 1329, 1234,
1
1166, 1111, 1066, 854 cm−1; H NMR (500 MHz, CDCl3) δ
2.49−2.52 (m, 2H, CH2), 2.74−2.77 (m, 2H, CH2), 4.44 (s,
1H, CH), 4.79 (s, 2H, NH2), 7.40 (d, J = 8.0 Hz, 2H, HAr),
561
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563

ACS Combinatorial Science
Technology Note
substituted 4H-chromenes as anticancer agents. Bioorg. Med. Chem.
Lett. 2012, 22, 4458−4461.
(4) Makawana, J. A.; Patel, M. P.; Patel, R. G. Synthesis and
antimicrobial evaluation of new pyrano [4,3-b]pyran and pyrano[3,2-
c]chromene derivatives bearing a 2-thiophenoxyquinoline nucleus.
Arch. Pharm. 2012, 345, 314−322.
(5) Saundane, A. R.; Vijaykumar, K.; Vaijinath, A. V. Synthesis of
novel 2-amino-4-(5′-substituted-2′-phenyl-1H-indol-3′-yl)-6-aryl-4H-
pyran-3-carbonitrile derivatives as antimicrobial and antioxidant
agents. Bioorg. Med. Chem. Lett. 2013, 23, 1978−1984.
(6) Venkatesham, A.; Rao, R. S.; Nagaiah, K.; Yadav, J. S.;
RoopaJones, G.; Basha, S. J.; Sridhar, B.; Addlagatta, A. Synthesis of
new chromeno-annulated cis-fused pyrano[3,4-c]pyran derivatives via
domino Knoevenagel-hetero-Diels-Alder reactions and their biological
evaluation towards antiproliferative activity. MedChemComm 2012, 3,
652−658.
(7) Kang, S. S.; Cooper, G.; Dunne, S. F.; Luan, C. H.; Surmeier, D.
J.; Silverman, R. B. Antagonism of L-type Ca2+ channels Cav1.3 and
Cav1.2 by 1,4-dihydropyrimidines and 4H-pyrans as dihydropyridine
mimics. Bioorg. Med. Chem. 2013, 21, 4365−4373.
(8) (a) Kumar, D.; Reddy, V. B.; Sharad, S.; Dube, U.; Kapur, S. A
facile one-pot green synthesis and antibacterial activity of 2-amino-4H-
pyrans and 2-amino-5-oxo-5,6,7,8-tetrahydro-4H-chromenes. Eur. J.
Med. Chem. 2009, 44, 3805−3809. (b) Litvinov, Y. M.; Shestopalov, A.
M. Synthesis, structure, chemical reactivity, and practical significance
of 2-amino-4H-pyrans. In Advances in Heterocyclic Chemistry; Katritzky,
A. R., Ed.; Academic Press: New York, 2011; Vol. 103, pp 175−260.
(9) Tian, J. J.; Guo, H. Y. New progress in the synthesis of pyrane
derivatives via multicomponent reactions. Chin. J. Org. Chem. 2011, 31,
2009−2018.
(10) Balalaie, S.; Bararjanian, M.; Sheikh-Ahmadi, M.; Hekmat, S.;
Salehi, P. Diammonium hydrogen phosphate: an efficient and versatile
catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran
derivatives in aqueous media. Synth. Commun. 2007, 37, 1097−1108.
(11) Lian, X. Z.; Huang, Y.; Li, Y. Q.; Zheng, W. J. A green synthesis
of tetrahydrobenzo[b]pyran derivatives through three-component
condensation using N-methylimidazole as organocatalyst. Monatsh.
Chem. 2008, 139, 129−131.
(12) Khan, A. T.; Lal, M.; Ali, S.; Khan, M. M. One-pot three-
component reaction for the synthesis of pyran annulated heterocyclic
compounds using DMAP as a catalyst. Tetrahedron Lett. 2011, 52,
5327−5332.
144.0, 161.5, 179.3 ppm; Anal. Calcd for C22H15N3O2: C, 74.78;
H, 4.28; N, 11.89. Found: C, 74.60; H, 4.45; N, 12.03.
Compound 7{32,5,1}. White solid; IR (KBr): 3481, 3298,
3196, 2860, 2189, 1627, 1527, 1338, 1107, 750 cm−1; 1H NMR
(500 MHz, DMSO-d6) δ 6.64 (d, J = 9.0 Hz, 1H, HAr), 7.22
(d, J = 9.0 Hz, 1H, HAr), 7.59−7.65 (m, 4H, NH2 and HAr),
7.71 (t, J = 8.0 Hz, 1H, HAr), 7.93 (d, J = 8.0 Hz, 1H, HAr),
8.02 (s, 1H, HAr), 8.29 (t, J = 7.0 Hz, 2H, HAr), 11.4 (s, 1H,
NH) ppm; 13C NMR (125 MHz, DMSO-d6) δ 51.6, 53.6,
111.1, 113.7, 118.8, 121.3, 121.4, 123.3, 123.4, 125.3, 127.1,
127.6, 128.0, 128.2, 133.8, 136.1, 143.6, 144.3, 148.8, 161.6,
179.7 ppm; Anal. Calcd for C21H12N4O4: C, 65.62; H, 3.15; N,
14.58. Found: C, 65.80; H, 2.96; N, 14.66.
Compound 7{32,9,1}. White solid; IR (KBr): 3396, 3186,
2968, 2362, 2202, 1743, 1506, 1390, 754 cm−1; 1H NMR (500
MHz, DMSO-d6) δ 3.02 (s, 3H, CH3), 3.36 (s, 3H, CH3), 7.03
(d, J = 8.5 Hz, 1H, HAr), 7.77 (s, 2H, NH2.), 8.17 (d, J = 8.5
Hz, 1H, HAr), 8.19 (s, 1H, HAr), 11.3 (s, 1H, NH) ppm; 13C
NMR (125 MHz, DMSO-d6) δ 28.1, 29.8, 48.0, 56.6, 86.5,
109.9, 117.1, 120.3, 126.5, 135.2, 143.0, 149.1, 150.1, 153.0,
158.9, 160.1, 178.7 ppm; Anal. Calcd for C17H12N6O6: C,
51.52; H, 3.05; N, 21.21. Found: C, 51.70; H, 2.91; N, 21.39.
Compound 8{33,3,1}. Light yellow solid; IR (KBr): 3471,
3362, 3194, 2929, 2193, 1712, 1589, 1361, 1026, 781 cm−1; 1H
NMR (500 MHz, DMSO-d6) δ 2.34 (t, J = 4.5 Hz, 2H, CH2),
2.88 (t, J = 4.5 Hz, 2H, CH2), 7.48 (d, J = 7.0 Hz, 1H, HAr),
7.62 (s, 2H, NH2), 7.71 (t, J = 7.5 Hz, 1H, HAr), 7.87 (t, J =
8.0 Hz, 1H, HAr), 8.00 (t, J = 9.0 Hz, 2H, HAr), 8.35 (d, J =
8.0 Hz, 1H, HAr) ppm; 13C NMR (125 MHz, DMSO-d6) δ
25.5, 33.6, 51.4, 57.6, 116.3, 118.1, 121.5, 122.5, 125.5, 129.2,
129.5, 130.4, 131.8, 132.8, 141.2, 141.8, 161.1, 178.3, 200.6,
203.6 ppm; Anal. Calcd for C20H12N2O3: C, 73.16; H, 3.68; N,
8.53. Found: C, 72.98; H, 3.85; N, 8.66.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H NMR and 13C NMR spectra of all new com-
pounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
(13) Sun, W. B.; Zhang, P.; Fan, J.; Chen, S. H.; Zhang, Z. H.
Lithium bromide as a mild, efficient, and recyclable catalyst for the
one-pot synthesis of tetrahydro-4H-chromene derivatives in aqueous
media. Synth. Commun. 2010, 40, 587−594.
(14) Wang, H. J.; Lu, J.; Zhang, Z. H. Highly efficient three-
component, one-pot synthesis of dihydropyrano[3,2-c]chromene
derivatives. Monatsh. Chem. 2010, 141, 1107−1112.
(15) Khurana, J. M.; Nand, B.; Saluja, P. DBU: a highly efficient
catalyst for one-pot synthesis of substituted 3,4-dihydropyrano[3,2-
c]chromenes, dihydropyrano[4,3-b]pyranes, 2-amino-4H-benzo[h]
chromenes and 2-amino-4H benzo[g]chromenes in aqueous medium.
Tetrahedron 2010, 66, 5637−5641.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: zhanhui@mail.nankai.edu.cn. Fax: +86-311-80787431.
Funding
This work is financially supported by the National Natural
Science Foundation of China (20872025 and 21272053),
Nature Science Foundation of Hebei Province (B2011205031),
and the Training Programs of Innovation and Entrepreneurship
for Undergraduates of Hebei Province (201310094021).
(16) Dekamin, M. G.; Eslami, M.; Maleki, A. Potassium phthalimide-
N-oxyl: a novel, efficient, and simple organocatalyst for the one-pot
three-component synthesis of various 2-amino-4H-chromene deriva-
tives in water. Tetrahedron 2013, 69, 1074−1085.
Notes
The authors declare no competing financial interest.
REFERENCES
(17) Xu, J. C.; Li, W. M.; Zheng, H.; Lai, Y. F.; Zhang, P. F. One-pot
synthesis of tetrahydrochromene derivatives catalyzed by lipase.
Tetrahedron 2011, 67, 9582−9587.
■
(1) Wickel, S. M.; Citron, C. A.; Dickschat, J. S. 2H-pyran-2-ones
from trichoderma viride and trichoderma asperellum. Eur. J. Org.
Chem. 2013, 2906−2913.
(18) Islami, M. R.; Mosaddegh, E. Ce(SO4)2·4H2O as a recyclable
catalyst for an efficient, simple, and clean synthesis of 4H-
Benzo[b]pyrans. Phosphorus, Sulfur Silicon Relat. Elem. 2009, 184,
3134−3138.
(19) Sabitha, G.; Arundhathi, K.; Sudhakar, K.; Sastry, B. S.; Yadav, J.
S. Cerium(III) chloride-catalyzed one-pot synthesis of
tetrahydrobenzo[b]pyrans. Synth. Commun. 2009, 39, 433−442.
(2) Wang, S.; Qi, Q. Z.; Li, C. P.; Ding, G. H.; Kim, S. H.
Photoswitching of bisthienylethene using 2D-π-A type pyran-based
fluorescent dye for rewritable optical storage. Dyes Pigm. 2011, 89,
188−192.
(3) Patil, S. A.; Wang, J.; Li, X. S.; Chen, J. J.; Jones, T. S.; Hosni-
Ahmed, A.; Patil, R.; Seibel, W. L.; Li, W.; Miller, D. D. New
562
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563

ACS Combinatorial Science
Technology Note
(20) Gao, S. J.; Tsai, C. H.; Tseng, C.; Yao, C. F. Fluoride ion
catalyzed multicomponent reactions for efficient synthesis of 4H-
chromene and N-arylquinoline derivatives in aqueous media.
Tetrahedron 2008, 64, 9143−914.
(21) Ranu, B. C.; Banerjee, S.; Roy, S. A task specific basic ionic
liquid, [bmIm]OH-promoted efficient, green and one-pot synthesis of
tetrahydrobenzo[b]pyran derivatives. Indian J. Chem. 2008, 47B,
1108−1112.
(22) Safaei, H. R.; Shekouhy, M.; Rahmanpur, S.; Shirinfeshan, A.
Glycerol as a biodegradable and reusable promoting medium for the
catalyst-free one-pot three component synthesis of 4H-pyrans. Green
Chem. 2012, 14, 1696−1704.
(23) Revanna, C. N.; Swaroop, T. R.; Raghavendra, G. M.;
Bhadregowda, D. G.; Mantelingu, K.; Rangappa, K. S. Practical and
green protocol for the synthesis of substituted 4H-chromenes using
room temperature ionic liquid choline chloride-urea. J. Heterocycl.
Chem. 2012, 49, 851−855.
(24) Yang, J.; Li, H. Q.; Li, M. H.; Peng, J. J.; Gu, Y. L.
Multicomponent reactions of β-ketosulfones and formaldehyde in a
bio-based binary mixture solvent system composed of meglumine and
gluconic acid aqueous solution. Adv. Synth. Catal. 2012, 354, 688−700.
(25) (a) Mattioni, B. E.; Kauffman, G. W.; Jurs, P. C.; Custer, L. L.;
Durham, S. K.; Pearl, G. M. Predicting the genotoxicity of secondary
and aromatic amines using data subsetting to generate a model
ensemble. J. Chem. Inf. Comput. Sci. 2003, 43, 949−963. (b) Mozdarani,
H.; Fadaei, S. Similar cytogenetic effects of sodium meglumine
diatrizoate and sodium meglumine ioxithalamate in lymphocytes of
patients undergoing brain CT scan. Toxicol. Lett. 1998, 98, 25−30.
(26) Gu, Y. L. Multicomponent reactions in unconventional solvents:
state of the art. Green Chem. 2012, 14, 2091−2128.
easy access of fully decorated 4H-pyran scaffolds and its rearrangement
to 2-pyridone nucleus in aqueous media. Tetrahedron Lett. 2012, 53,
4687−4691.
(33) Kumar, B. S.; Srinivasulu, N.; Udupi, R. H.; Rajitha, B.; Reddy,
Y. T.; Reddy, P. N.; Kumar, P. S. An efficient approach towards three
component coupling of one pot reaction for synthesis of functionalized
benzopyrans. J. Heterocycl. Chem. 2006, 43, 1691−1693.
(34) Elinson, M. N.; Ilovaisky, A. I.; Merkulova, V. M.; Zaimovskaya,
T. A.; Nikishin, G. I. Electrocatalytic multicomponent assembling of
aldehydes, N-alkyl barbiturates and malononitrile: an efficient
approach to pyrano[2,3-d]pyrimidines. Mendeleev Commun. 2011, 21,
122−124.
(35) Wang, L. M.; Jiao, N.; Qiu, J.; Yu, J. J.; Liu, J. Q.; Guo, F. L.; Liu,
Y. Sodium stearate-catalyzed multicomponent reactions for efficient
synthesis of spirooxindoles in aqueous micellar media. Tetrahedron
2010, 66, 339−343.
(36) Raghuvanshi, D. S.; Singh, K. N. An efficient protocol for
multicomponent synthesis of spirooxindoles employing L-proline as
catalyst at room temperature. J. Heterocycl. Chem. 2010, 47, 1323−
1327.
(37) He, Y.; Guo, H. Y.; Tian, J. J. A simple three-component
synthesis of spiro-pyran derivatives. J. Chem. Res. 2011, 528−530.
(27) (a) Wang, H. J.; Mo, L. P.; Zhang, Z. H. Cerium ammonium
nitrate-catalyzed multicomponent reaction for efficient synthesis of
functionalized tetrahydropyridines. ACS Comb. Sci. 2011, 13, 181−
185. (b) Zhang, X. N.; Li, Y. X.; Zhang, Z. H. Nickel chloride-catalyzed
one-pot three-component synthesis of pyrazolophthalazinyl spiroox-
indoles. Tetrahedron 2011, 67, 7426−7430. (c) Deng, J.; Mo, L. P.;
Zhao, F. Y.; Zhang, Z. H.; Liu, S. X. One-pot, three-component
synthesis of a library of spirooxindole-pyrimidines catalyzed by
magnetic nanoparticle supported dodecyl benzenesulfonic acid in
aqueous media. ACS Comb. Sci. 2012, 14, 335−341. (d) Zhang, Z. H.;
Zhang, X. N.; Mo, L. P.; Li, Y. X.; Ma, F. P. Catalyst-free synthesis of
quinazoline derivatives using low melting sugar-urea-salt mixture as a
solvent. Green Chem. 2012, 14, 1502−1506. (e) Deng, J.; Mo, L. P.;
Zhao, F. Y.; Hou, L. L.; Yang, L.; Zhang, Z. H. Sulfonic acid supported
on hydroxyapatite-encapsulated-γ-Fe2O3 nanocrystallites as a magneti-
cally separable catalyst for one-pot reductive amination of carbonyl
compounds. Green Chem. 2011, 13, 2576−2584. (f) Liu, Y. H.; Deng,
J.; Gao, J. W.; Zhang, Z. H. Triflic acid-functionalized silica-coated
magnetic nanoparticles as a magnetically separable catalyst for
synthesis of gem-dihydroperoxides. Adv. Synth. Catal. 2012, 354,
441−447.
(28) Banerjee, S.; Horn, A.; Khatri, H.; Sereda, G. A green one-pot
multicomponent synthesis of 4H-pyrans and polysubstituted aniline
derivatives of biological, pharmacological, and optical applications
using silica nanoparticles as reusable catalyst. Tetrahedron Lett. 2011,
52, 1878−1881.
(29) Balalaie, S.; Sheikh-Ahmadi, M.; Bararjanian, M. Tetra-methyl
ammonium hydroxide: An efficient and versatile catalyst for the one-
pot synthesis of tetrahydrobenzo[b]pyran derivatives in aqueous
media. Catal. Commun. 2007, 8, 1724−1728.
(30) Dandia, A.; Parewa, V.; Jain, A. K.; Rathore, K. S. Step-
economic, efficient, ZnS nanoparticle-catalyzed synthesis of spiroox-
indole derivatives in aqueous medium via Knoevenagel condensation
followed by Michael addition. Green Chem. 2011, 13, 2135−2145.
(31) Saeedi, M.; Heravi, M. M.; Beheshtiha, Y. S.; Oskooie, H. A.
One-pot three-component synthesis of the spiroacenaphthylene
derivatives. Tetrahedron 2010, 66, 5345−5348.
(32) Bhattacharyya, P.; Pradhan, K.; Paul, S.; Das, A. R. Nano
crystalline ZnO catalyzed one pot multicomponent reaction for an
563
dx.doi.org/10.1021/co400107j | ACS Comb. Sci. 2013, 15, 557−563