An efficient three-component synthesis of amino-substituted pyrano[3,2-b] pyranones

Article abstract of DOI:10.3184/174751913X13796142561782

A green, efficient and mild one-pot synthesis of pyrano[3,2-b]pyran derivatives via a three component reaction in the ionic liquid [bmim]BF ₄ is reported. This method has the advantages of environmental friendliness, operational simplicity, high yields and reuse of the ionic liquid.

Full text of DOI:10.3184/174751913X13796142561782

638 RESEARCH PAPER
OCTOBER, 638–641
JOURNAL OF CHEMICAL RESEARCH 2013
An efficient three-component synthesis of amino-substituted pyrano[3,2-b]
pyranones
Xiang-Xue Menga, Bai-Xiang Dua, Bo Zhaoa, Yu-Ling Lia* and Cai-Fa Chenb
aSchool of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal
University, Xuzhou 221116, P.R. China
bThe Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province, Jiangsu Normal University, Xuzhou 221116, P.R. China
A green, efficient and mild one-pot synthesis of pyrano[3,2-b]pyran derivatives via a three component reaction in the ionic liquid
[bmim]BF4 is reported. This method has the advantages of environmental friendliness, operational simplicity, high yields and
reuse of the ionic liquid.
Keywords: multi-component reaction, pyrano[3,2-b]pyranone, ionic liquid
Over the past decades, multicomponent reactions (MCRs) have
proved to be very powerful and efficient bond-forming tools in
organic, combinatorial and medicinal chemistry in the context
of green chemistry.1,2 MCRs with environmentally benign
methods have been one of most important topics of green
chemistry. One approach to reduce the environmental impact
of a reaction is to conduct them in ionic liquid (IL) media.
ILs have attracted extensive interest as benign reaction media
in organic synthesis in recent years because of their unique
properties of non-volatility, nonflammability, recyclability, and
ability to dissolve a wide range of materials.3
the Cu(OTf)2 catalysed synthesis of spiropyrano[3,2-b]pyran-
4(8H)-ones via one-pot three component reaction between
isatin, kojic acid, and active methylenes in 1,2-dichloroethane.17
Banitaba et al.18 prepared pyrano[3,2-b]pyran derivatives by
the reaction of aromatic aldehydes, malononitrile and kojic
acid in a heated aqueous phase using ultrasound irradiation.
These methods usually require forcing conditions, complex
synthetic pathways and often reaction in organic solvents.
Thus, in view of the importance of pyranopyranones for their
diverse therapeutic activity and in continuation of our interest
in the development of new synthetic methods in heterocyclic
chemistry,19,20 we considered it useful to develop a general
rapid, environmentally benign and easy synthetic protocol for a
variety of pyrano[3,2-b]pyranone derivatives.
We now report a three-component one-pot synthesis of
pyrano[3,2-b]pyranones in ionic liquid medium (Scheme 1).
When three components of aromatic aldehyde 1, malononitrile
or cyanoacetate 2 and kojic acid 3 were treated in ionic liquid
[bmim]BF4 in the presence of Et3N at room temperature for
a few hours, the pyrano[3,2-b]pyranone derivatives 4 were
obtained. To the best of our knowledge, this methodology has
not been reported in the literature.
Pyran and pyran derivatives are important heterocyclic
compounds. They are important to the synthetic chemists
due to their pronounced biological and pharmacological
activities such as antibacterial,4 anti-fungal,5 antidiabetic,6
antiproliferative,7 antimicrobial,8 antitumour,9 anti-HIV,10
antimalarial.11 On the other hand, pyranopyranones are also
known for their biological properties including antioxidant
and cytotoxic activities.12 So, it is very important to synthesise
the pyran and pyranopyranone derivatives. A good number
of methods have been already reported for the synthesis
of pyran derivatives. But, so far only a few methods are
available for the synthesis of pyranopyranones. Piao and
Imafuku prepared pyrano[3,2-b]pyran-4-one derivatives by
the reaction of substituted cinnamonitriles and 5-hydroxy-
2-(hydroxymethyl)-4H-pyran-4-one (kojic acid) in absolute
ethanol in the presence of organic bases like piperidine.13 Shi
et al.14 synthesised pyrano[3,2-c]pyran-5-one derivatives via
substituted cinnamonitriles and the active methylene carbonyl
compound 4-hydroxy-6-methylpyran-2-one at 90 °C in an
aqueous phase in the presence of triethylbenzylammonium
chloride (TEBA), Wang et al.15 developed a rapid and
efficient method to synthesise a series of pyrano[3,2-c]
pyrans by the reaction of aromatic aldehydes, malononitrile or
cyanoacetate and 4-hydroxy-6-methylpyran-2-one in EtOH at
room temperature in the presence of KF-Al2O3. Shestopalov
synthesised a pyrano[3,2-b]pyran derivative by the reaction of
4-trifluoromethylthiobenzaldehyde, malonodinitrile and kojic
acidinethanolcatalysedbyEt3N.16 Parthasarathyetal.17 reported
Results and discussion
We carried out the one-pot three-component reaction of
4-chlorobenzaldehyde 1a, malononitrile 2 and kojic acid 3 as
a model reaction. In this reaction, we found that catalysts have
significant effects on the reaction time and yields (Table 1). The
results indicated that this three-component reaction did not take
place in the presence of proton acids such as TsOH or classical
Lewis acids such as ZnCl2, and Yb(OTf)3 as catalysts in the
Table 1 Optimisation of the reaction conditionsa
Entry
Catalyst/equiv.
Solvent
Time/h
Yield/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
TsOH (1.0)
ZnCl2 (1.0)
Yb(OTf)3 (1.0)
Et3N(1.0)
Pyridine(1.0)
Piperidine(1.0)
NH4OAc(1.0)
Et3N(1.0)
Et3N(1.0)
Et3N(1.0)
Et3N(0)
Et3N(0.5)
[bmim]BF4
[bmim]BF4
[bmim]BF4
[bmim]BF4
[bmim]BF4
[bmim]BF4
[bmim]BF4
EtOH
CH3CN
DMF
[bmim]BF4
[bmim]BF4
[bmim]BF4
24
24
24
3
3
3
0
0
0
80
55
45
57
0
0
50
0
52
78
3
24
24
3
3
3
Scheme 1 The reaction of aldehyde 1, malononitrile or cyanoacetate 2
and kojic acid 3 in ionic liquid [bmim]BF4.
Et3N(2.0)
3
aReaction conditions: 1 mmol of 4-chlorobenzaldehyde, 1 mmol of
malononitrile, 1 mmol of kojic acid, room temperature.
bIsolated yields.
* Correspondent. E-mail: ylli19722@163.com
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JOURNAL OF CHEMICAL RESEARCH 2013 639
a
Table 2 Synthesis of 4 in ionic liquid [bmim]BF4
ionic liquid [bmim]BF4 at room temperature for 24 h, (Table 1,
entries 1–3). Then, we carried out the reaction using bases as
the catalysts under the same reaction conditions, using Et3N,
pyridine, piperidine, and ammonium acetate (Table 1, entries
4–7). To our delight, the desired condensation product 4a was
obtained in 80%, 55%, 45%, and 57% yields, respectively,
which meant that this three-component condensation reaction of
4-chlorobenzaldehyde 1a, malononitrile 2 and kojic acid 3 could
proceed smoothly catalysed by bases. As shown in Table 1, Et3N
was found to be the most effective catalyst in terms of reaction
time and yields (Table 1, entry 4). Furthermore, we found that
the yields of 4a were improved as the amount of Et3N increased
from 0.5 equiv. to 1.0 equiv., and the yields had a plateau when
the amount of ammonium acetate was further increased from
1.0 equiv. to 2.0 equiv. (Table 1, entries 4, 11–13). Therefore,
1.0 equiv. of Et3N was considered to be the most suitable.
Different solvents, for example, EtOH, CH3CN, and DMF, were
tested in the presence of Et3N as catalyst, but unfortunately they
resulted in low yields or no reaction (Table 1, entries 8–10).
Therefore, the best reaction conditions were obtained by using
1.0 equiv. of Et3N as the catalyst in the ionic liquid [bmim]BF4
at room temperature.
Entry
Ar
R
Product
Time/h
Yields/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
4-ClC6H4
2-ClC6H4
3-ClC6H4
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
3
0.3
5
0.5
4.8
5
80(80,78,78)c
86
82
72
79
79
76
79
85
67
83
74
72
76
80
81
81
3,4-Cl2C6H3
2,3-Cl2C6H3
2-BrC6H4
2-CF3C6H4
3-CF3C6H4
4-CH3OC6H4
3-CH3OC6H4
4-CH3C6H4
3-FC6H4
3-NO2C6H4
4-BrC6H4
2,4-Cl2C6H3 COOMe
2-CF3C6H4
4-ClC6H4
5
5
4.5
3
4.7
0.5
5
1.2
15
10
9
COOMe
COOEt
aReaction conditions: 2 mL ionic liquid, 1 mmol aromatic aldehyde, 1 mmol
malononitrile or cyanoacetate, 1 mmol kojic acid, rt.
bIsolated yields.
cThe ionic liquid was reused for three runs.
they were easily separated by simple filtration from the mixture
of water and the ionic liquid, the filtrate was then extracted
with ether and dried at 90 °C in a vacuum for several hours to
be then recycled. As shown in Table 2, the reaction medium can
be recycled at least three times without significant decrease of
the yields, ranging from 80 to 78%.
A series of aromatic aldehydes were employed under similar
circumstances to evaluate the substrate scope of this reaction.
The results are summarised in Table 2. The structures of
1
compounds 4a–q were fully confirmed by melting points, H
NMR, IR and HRMS. The structure of product 4i was further
confirmed by X-ray crystallography (Fig. 1).21 The electronic
effect of the aryl group on this reaction was investigated as well.
Under optimised reaction conditions aldehydes having either
an electron withdrawing or an electron donating substituent
readily provided pyrano[3,2-b]pyran derivatives in high yields
(Table 2). Therefore, the electronic nature of the substrate has
no significant effect on this reaction.
Based on the above results, a plausible mechanism of this
reaction was proposed in Scheme 2. First, aldehyde 1 and
malononitrile or cyanoacetate 2 underwent Knoevenagel
condensation to afford intermediate 5. Then, Michael addition
of kojic acid 3 to 5 would furnish intermediate 6. Finally, the
product 4 was obtained by an intramolecular cyclisation and
dehydration.
Experimental
Melting points were determined on a melting point apparatus and are
uncorrected. IR spectra were recorded on a Tensor 27 spectrometer
1
in KBr. H NMR spectra were obtained from solution in DMSO-d6
with Me4Si as an internal standard using a Bruker-400 spectrometer.
HRMS data were obtained using a MicroTOF-QII instrument. The
single-crystal growth was carried out in ethanol at room temperature.
X-ray crystallographic analysis was performed using a Rigaku Saturn
diffractometer. Crystallographic data for the structures of 4i reported
in this paper have been deposited at the Cambridge Crystallographic
Data Centre No. CCDC-926835. Crystal data for 4i:C17H16N2O6,
colourless, crystal dimension 0.26×0.20×0.12 mm, Monoclinic, space
group P2(1)/n, a=9.9437(16) nm, b=11.8220(19) nm, c=14.259(2)
nm, β=105.844(2)°, V=1612.5(4) nm3, Mr=394.79, Z=4, Dc=1.418 g
cm–3, λ=0.71073 nm, μ(Mokα)=0.109 mm–1, F(000)=720, S=1.042,
R1 =0.0398, wR2 = 0.1133.
We used the preparation of 4a as a model to study the
recovery and reuse of the ionic liquid [bmim]BF4. Because of
the poor solubility of the products in ionic liquids and water,
CN
CN
R
Et3N
-H2O
Ar-CH
C
+
Ar-CHO
R
2
5
1
Et3N
H
Ar
O
O
O
5
O
R
O
O
HO
HO
HO
Et3N
-H
C
N
O
OH
O
6
3
Ar
O
Ar
O
R
NH2
R
H
O
O
HO
HO
Et3N
O
NH
O
7
4
Fig. 1 X-Ray crystal structure of compound 4i.
Scheme 2 A plausible reaction mechanism.
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640 JOURNAL OF CHEMICAL RESEARCH 2013
Synthesis of 4; general procedure
2-Amino-4-(4-methoxyphenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4i): M.p. 220–223 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.20 (d, 4H, J=8.8, ArH), 6.95 (d, 2H, J=8.8, NH2),
6.33 (s, 1H,=CH), 5.71 (s, 1H, OH), 4.74 (s, 1H, CH), 4.10–4.24 (m,
2H, CH2), 3.75 (s, 3H, OCH3); IR (KBr, ν, cm–1): 3349, 3336, 2199, 1621;
HRMS calcd for C17H14N2O5Na (M+Na)+: requires 349.0800, found:
349.0805.
2-Amino-4-(3-methoxyphenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4j): M.p. 268–269 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.30–7.34 (m, 1H, ArH), 7.25 (s, 2H, NH2), 6.89–
6.91 (m, 1H, ArH), 6.83 (s, 2H, ArH), 6.35 (s, 1H, =CH), 5.70 (s, 1H, OH),
4.77 (s, 1H, CH), 4.12–4.25 (m, 2H, CH2), 3.76 (s, 3H, OCH3); IR (KBr, ν,
cm–1): 3350, 3341, 2220, 1620; HRMS calcd for C17H14N2O5Na (M+Na)+:
requires 349.0800, found: 349.0810.
2-Amino-4-(4-methylphenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4k): M.p. 204–206 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.15–7.21 (m, 6H, ArH+NH2), 6.33 (s, 1H, =CH),
5.72 (s, 1H, OH), 4.74 (s, 1H, CH), 4.10–4.23 (m, 2H, CH2), 2.29 (s,
3H, CH3); IR (KBr, ν, cm–1): 3575, 3324, 2193, 1629; HRMS calcd for
C17H14N2O4Na (M+Na)+: requires 333.0851, found: 333.0835.
2-Amino-4-(3-fluorophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4l): M.p. 220–222 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.45 (s, 1H, ArH), 7.27 (s, 2H, NH2), 7.16 (s, 3H,
ArH), 6.35 (s, 1H, =CH), 5.72 (s, 1H, OH), 4.88 (s, 1H, CH), 4.12–4.24
(m, 2H, CH2); IR (KBr, ν, cm–1): 3368, 3321, 2203, 1650; HRMS calcd for
C16H11FN2O4Na (M+Na)+: requires 337.0601, found: 337.0574.
2-Amino-4-(3-nitrophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4m): M.p. 215–217 °C; 1H NMR
(DMSO-d6, δ, ppm): 8.18 (s, 2H, ArH), 7.81 (s, 1H, ArH), 7.72 (s, 1H,
ArH), 7.38 (s, 2H, NH2), 6.36 (s, 1H, =CH), 5.71 (s, 1H, OH), 5.14 (s, 1H,
CH), 4.11–4.23 (m, 2H, CH2); IR (KBr, ν, cm–1): 3384, 3319, 2189, 1639;
HRMS calcd for C16H11N3O6Na (M+Na)+: requires 364.0546, found:
364.0550.
Et3N(1 mmol) was added to a solution of aromatic aldehyde 1 (1 mmol),
malononitrile or cyanoacetate 2 (1 mmol), kojic acid 3 (1 mmol) in
ionic liquid [bmim]BF4 (2 mL). The mixture was then stirred at room
temperature. After completion of the reaction as indicated by TLC,
water (5 mL) was added and the product was filtered off and washed
with water. The remaining aqueous layer containing the ionic liquid
was extracted with ether three times to remove the organic impurity,
and then dried under vacuum at 90 °C for about 15 h to afford the
ionic liquid, which was used in the subsequent runs without further
purification. The crude product was purified by recrystallisation from
ethanol to give 4 as a white powder.
2-Amino-4-(4-chlorophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4a): M.p. 198–200 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.46 (d, 2H, J=8.8 Hz, ArH), 7.34 (d, 2H, J=8.8 Hz
ArH), 7.29 (s, 2H, NH2), 6.34 (s, 1H,=CH), 5.70 (s, 1H, OH), 4.11–4.24
(m, 2H, CH2), 4.87 (s, 1H, CH); IR (KBr, ν, cm–1): 3355, 3198, 2197, 1650;
HRMS calcd for C16H11ClN2O4Na (M+Na)+: requires 353.0305, found:
353.0315.
2-Amino-4-(2-chlorophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4b): M.p. 201–203 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.48–7.50 (m, 1H, ArH), 7.34–7.42 (m, 3H, ArH),
7.26 (s, 2H, NH2), 6.35 (s, 1H, =CH), 5.70 (t, 1H, J=6.0 Hz, OH), 5.27 (s,
1H, CH), 4.07–4.22 (m, 2H, CH2); IR (KBr, ν, cm–1): 3393, 3326, 2201,
1649; HRMS calcd for C16H11ClN2O4Na (M+Na)+: requires 353.0305,
found: 353.0316.
2-Amino-4-(3-chlorophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4c): M.p. 201–202 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.38–7.46 (m, 3H, ArH), 7.31 (s, 2H, NH2), 7.27–7.29
(m, 1H, ArH), 6.35 (s, 1H, =CH), 5.70 (s, 1H, OH), 4.89 (s, 1H, CH),
4.11–4.24 (m, 2H, CH2); IR (KBr, ν, cm–1): 3375, 3331, 2198, 1650; HRMS
calcd for C16H11ClN2O4Na (M+Na)+: requires 353.0305, found: 353.0305.
2-Amino-4-(3,4-dichlorophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4d): M.p. 228–230 °C; 1H
NMR (DMSO-d6, δ, ppm): 7.67 (d, 1H, J=2.0 Hz ArH), 7.48 (dd, 1H,
J1 =8,4 Hz, J2 =2.0 Hz, ArH), 7.43(d, 1H, J=8.4 Hz, ArH), 7.31 (s, 2H,
NH2), 6.35 (s, 1H, =CH), 5.71 (t, 1H, J=6.0 Hz, OH), 5.29 (s, 1H, CH),
4.09–4.22 (m, 2H, CH2); IR (KBr, ν, cm–1): 3339, 3193, 2195, 1644;
HRMS calcd for C16H10Cl2N2O4Na (M+Na)+: requires 386.9915, found:
386.9905.
2-Amino-4-(4-bromophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4n): M.p. 224–226 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.42–7.46 (m, 2H, ArH), 7.35 (m, 1H, ArH), 7.24–
7.28 (m, 3H, ArH+NH2), 6.30 (s, 1H, =CH), 5.71 (s, 1H, OH), 5.26 (s, 1H,
CH), 4.10–4.15 (m, 2H, CH2); IR (KBr, ν, cm–1): 3433, 3321, 2199, 1621;
HRMS calcd for C16H11BrN2O4 (M+Na)+: requires 396.9800, found:
396.9806.
Methyl 2-amino-4-(2,4-dichlorophenyl)-6-hydroxyethyl-8-oxo-
4H,8H-pyrano[3,2-b]pyran-3-carboxylate (4o): M.p. 230–232 °C; 1H
NMR (DMSO-d6, δ, ppm): 7.67 (d, 1H, J=2.0 Hz, ArH), 7.48 (m, 1H,
ArH), 7.43(d, 1H, J=8.4 Hz, ArH), 7.30 (s, 2H, NH2), 6.35 (s, 1H, =CH),
5.72 (t, 1H, J=6.0 Hz, OH), 5.30 (s, 1H, CH), 4.10–4.22 (m, 2H, CH2),
3.51 (s, 3H, OCH3); IR (KBr, ν, cm–1): 3339, 3193, 2195, 1644; HRMS
calcd for C17H13Cl2NO6Na (M+Na)+: requires 420.0018, found: 420.0030.
Methyl 2-amino-4-(2-trifluoromethylphenyl)-6-hydroxymethyl-8-oxo-
4H,8H-pyrano[3,2-b]pyran-3-carboxylate (4p): M.p. 227–229 °C; 1H
NMR (DMSO-d6, δ, ppm): δ : 7.60 (d, 1H, J=1.6 Hz, ArH), 7.48 (dd, 1H,
J1 =8.0 Hz, J2 =1.6 Hz, ArH), 7.40 (d, 1H, J=8.4 Hz, ArH), 7.31 (s, 2H,
NH2), 6.31 (s, 1H,=CH), 5.71 (t, 1H, J=6.0 Hz, OH), 5.32 (s, 1H, CH),
4.09–4.21 (m, 2H, CH2), 3.46 (s, 3H, OCH3); IR (KBr, ν, cm–1): 3339,
3193, 2195, 1644; HRMS calcd for C18H14F3NO6Na (M+Na)+: requires
420.0671, found: 420.0683.
2-Amino-4-(2,3-dichlorophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4e): M.p. 235–238 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.63 (s, 1H, ArH), 7.40–7.44 (m, 2H, ArH), 7.33
(s, 2H, NH2), 6.36 (s, 1H, =CH), 5.70 (s, 1H, OH), 5.38 (s, 1H, CH),
4.09–4.21 (m, 2H, CH2); IR (KBr, ν, cm–1): 3362, 3199, 2192, 1650;
HRMS calcd for C16H10Cl2N2O4Na (M+Na)+: requires 386.9915, found:
386.9904.
2-Amino-4-(2-bromophenyl)-6-hydroxymethyl-8-oxo-4H,8H-
pyrano[3,2-b]pyran-3-carbonitrile (4f): M.p. 225–227 °C; 1H NMR
(DMSO-d6, δ, ppm): 7.66 (dd, 1H, J1 =8.0 Hz, J2 =1.2 Hz, ArH), 7.42–
7.46 (m, 1H, ArH), 7.36 (dd, 1H, J1 =7.6 Hz, J2 =1.6 Hz, ArH), 7.26–7.30
(m, 3H, ArH), 6.35 (s, 1H, =CH), 5.69 (s, 1H, OH), 5.28 (s, 1H, CH),
4.07–4.22 (m, 2H, CH2); IR (KBr, ν, cm–1): 3433, 3321, 2199, 1621;
HRMS calcd for C16H11BrN2O4Na (M+Na)+: requires 396.9800, found:
396.9805.
2-Amino-4-(2-trifluoromethylphenyl)-6-hydroxymethyl-8-oxo-
4H,8H-pyrano[3,2-b]pyran-3-carbonitrile (4g): M.p. 239–242 °C; 1H
NMR (DMSO-d6, δ, ppm): 7.76 (s, 2H, ArH), 7.55 (s, 2H, ArH), 7.31 (s,
2H, NH2), 6.33 (s, 1H, CH), 5.66 (s, 1H, OH), 5.08 (s, 1H, CH), 4.02–4.16
(m, 2H, CH2); IR (KBr, ν, cm–1): 3367, 3331, 2200, 1650; HRMS calcd for
C17H11F3N2O4Na (M+Na)+: requires 387.0569, found: 387.0567.
2-Amino-4-(3-trifluoromethylphenyl)-6-hydroxymethyl-8-oxo-
4H,8H-pyrano[3,2-b]pyran-3-carbonitrile (4h): M.p. 212–213 °C; 1H
NMR (DMSO-d6, δ, ppm): 7.64–7.71 (m, 4H, ArH), 7.32 (s, 2H, NH2),
6.35 (s, 1H, =CH), 5.71 (s, 1H, OH), 5.04 (s, 1H, CH), 4.10–4.24 (m,
2H, CH2); IR (KBr, ν, cm–1): 3370, 3329, 2199, 1649; HRMS calcd for
C17H11F3N2O4Na (M+Na)+: requires 387.0569, found: 387.0578.
Ethyl 2-amino-4-(4-chlorophenyl)-6-hydroxyethyl-8-oxo-4H,8H-
1
pyrano [3,2-b]pyran-3-carboxylate (4q): M.p. 228–230 °C; H NMR
(DMSO-d6, δ, ppm): 7.35 (d, 2H, J=8.4 Hz, ArH), 7.24 (d, 2H, J=8.4 Hz,
ArH), 7.83 (s, 2H, NH2), 6.30 (s, 1H, =CH), 5.67 (t, 1H, J=6.0 Hz, OH),
4.80 (s, 1H, CH), 4.18 (dd, 2H, J1 =17.2 Hz, J2 =5.6 Hz, CH2), 3.91 (dd,
2H, J1 =6.8 Hz, J2 =2.0 Hz, CH2), 0.98 (t, 3H, J=7.2 Hz, CH3); IR (KBr, ν,
cm–1): 3393, 3326, 2201, 1649; HRMS calcd for C18H16ClNO6Na
(M+Na)+: requires 400.0564, found: 400.0558.
Conclusions
In summary, we have synthesised the pyrano[3,2-b]pyran
derivatives via a three-component reaction in an ionic
liquid. These methods suffer from many advantages, such as
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JOURNAL OF CHEMICAL RESEARCH 2013 641
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operational simplicity, mild reaction conditions, higher yields
and environmental friendliness, as well as the reuse of the ionic
liquid, which could be reused three times without apparent loss
of activity.
7
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We are grateful to the National Natural Science Foundation of
China (No. 21104064, 21172188), Natural Science Foundation of
XuZhou Normal University (10XLR03), Research Grant from
the Innovation Project for Undergraduate of Jiangsu Province
(12ssjcxzd18), National Training Programs of Innovation and
Entrepreneurship for Undergraduates (201210320018) and
Priority Academic Program Development of Jiangsu Higher
Education Institutions for financial support.
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Received 16 June 2013; accepted 12 August 2013
Paper 1302013 doi: 10.3184/174751913X13796142561782
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