A highly efficient and recyclable silica-supported tungstic acid (STA) catalyst for the synthesis of pyrano[3,2-c]chromen-5-ones under solvent free conditions

Article abstract of DOI:10.1016/j.tet.2017.07.008

A simple, efficient, green and solvent-free procedure for the synthesis of pyrano[3,2-c]chromen-5-ones has been developed by multi-component condensation of 4-hydroxycoumarin, aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine in the presence of a catalytic amount of silica-supported tungstic acid (STA). The reaction transformation presumably occurs via Knoevenagel condensation, Michael addition, imine-enamine tautomerism intramolecular, O-cyclization, elimination of MeSH. The present environmentally benign protocol offers several advantages such as shorter reaction times, a wide range of functional group tolerance, use of an inexpensive heterogeneous catalyst, and high yield of products via a simple experimental and work-up procedure. The catalyst can be recovered and reused for at least four runs without any significant impact on the product yields.

Full text of DOI:10.1016/j.tet.2017.07.008

Accepted Manuscript
A highly efficient and recyclable silica-supported tungstic acid (STA) catalyst for the
synthesis of pyrano[3,2-c]chromen-5-ones under solvent free conditions
Amol Maruti Jadhav, Suresh Kumar Krishnammagari, Jong Tae Kim, Yeon Tae Jeong
PII:
S0040-4020(17)30725-1
10.1016/j.tet.2017.07.008
TET 28840
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 May 2017
Revised Date: 28 June 2017
Accepted Date: 5 July 2017
Please cite this article as: Jadhav AM, Krishnammagari SK, Kim JT, Jeong YT, A highly efficient and
recyclable silica-supported tungstic acid (STA) catalyst for the synthesis of pyrano[3,2-c]chromen-5-ones
under solvent free conditions, Tetrahedron (2017), doi: 10.1016/j.tet.2017.07.008.
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A highly efficient and recyclable silica-supported
tungstic acid (STA) catalyst for the synthesis of pyrano
[3,2-c]chromen-5-ones under solvent free conditions
Leave this area blank for abstract info.
Amol Maruti Jadhav1, Suresh Kumar Krishnammagari1, Jong Tae Kim, Yeon Tae Jeong*
Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of
Korea.

1
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Tetrahedron
journal homepage: www.elsevier.com
A highly efficient and recyclable silica-supported tungstic acid (STA) catalyst for the
synthesis of pyrano[3,2-c]chromen-5-ones under solvent free conditions
Amol Maruti Jadhav 1, Suresh Kumar Krishnammagari 1, Jong Tae Kim, Yeon Tae Jeong
Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A simple, efficient, green and solvent-free procedure for the synthesis of pyrano[3,2-c]chromen-
5-ones has been developed by multi-component condensation of 4-hydroxycoumarin, aldehydes
and (E)-N-methyl-1-(methylthio)-2-nitroethenamine in the presence of a catalytic amount of
silica-supported tungstic acid (STA). The reaction transformation presumably occurs via
Knoevenagel condensation, Michael addition, imine-enamine tautomerism intramolecular, O-
cyclization, elimination of MeSH. The present environmentally benign protocol offers several
advantages such as shorter reaction times, a wide range of functional group tolerance, use of an
inexpensive heterogeneous catalyst, and high yield of products via a simple experimental and
work-up procedure. The catalyst can be recovered and reused for at least four runs without any
significant impact on the product yields.
Available online
Keywords:
Pyrano[3,2-c]chromen-5-ones
Silica-supported tungstic acid
Heterogeneous catalyst
Solvent-free condition
One-pot synthesis
2009 Elsevier Ltd. All rights reserved
.
compounds can be used as cognitive enhancers for the treatment
of neurodegenerative diseases, including Alzheimerꢀs disease, as
well as for the treatment of schizophrenia and myoclonus.14
1. Introduction
Multicomponent reactions (MCRs) are special types of
synthetically useful organic reactions in which three or more
starting materials react to give a final product in a one-pot
procedure.1 MCRs have their inherent advantages such as short
reaction times, low manpower requirement, high atom economy
and simple purification processes. MCRs protocols can be used
for fragment based drug design2-4 and diversity-oriented
synthesis of heterocyclic compounds because of their simplicity,
efficiency, and high selectivity.5
Figure 1 Examples of biologically active pyranocoumarin derivatives.
Therefore, there is a strong need to develop a quick and
efficient synthetic method to access a biologically active
pyranocoumarin molecule. But, a literature scan showed that,
only one method has been developed so far for the synthesis of
this skeleton.15 However, these procedures suffer from relatively
long reaction times, low yields, the use of toxic organic solvents
and catalysts. Hence, the development of new and highly
efficient, protocol for the synthesis of pyrano[3,2-c]chromen-5-
ones derivatives is still highly desirable.
Chemistry of heterocyclic compounds has been ubiquitous in
natural
products,
biologically
active
agrochemicals,
pharmaceutical agents, organic materials, and several well-
designed molecules.6 Therefore, the interest for developing new,
versatile, and efficient synthesis of heterocyclic compounds have
been important in synthetic organic and bio-organic chemistry.
Pyrano[3,2-c]chromen-5-ones are a promising class of oxygen
containing heterocyclic compounds are widely found in nature
and gain much importance due to their broad series of biological
activities.7 For example, compound
A has antibacterial,
Currently, multi-component one-pot synthesis and solid
supported catalysts have gained much interest because of their
cost-effectiveness by reusability and ecological benefits.16–18
Environmentally friendly and inexpensive solid acids are
increasingly used due to their ease of handling and high catalytic
activities. In the course of the last few years, particularly silica-
antituberculosis, antimalarial activities, compound B, and C also
have antibacterial activity (Fig. 1).8 Similarly, some pyran
annulated heterocycles have
a wide range of biological
properties such as anti-coagulants,9 anticancer agents,10 anti-
anaphylactics,11 anti-tumoral,12 anti-HIV etc.13 Moreover, these
———
1
Both authors contributed equally to this manuscript
Corresponding author. Tel.: +82-51-629-6411; fax: +82-51-629-6408; e-mail: ytjeong@pknu.ac.kr

2
Tetrahedron
ACCEPTED MANUSCRIPT
supported acid catalysts have established numerous
excitingly, when STA was used, the reaction proceeded very
applications in modern organic synthesis as they may be easily
recovered and reused.16 In this connection, silica-supported
tungstic acid (STA) has attracted tremendous attention as a green
and solid acid catalyst to construct carbon–carbon and carbon–
heteroatom bonds in various organic trans-formations.17,18 It has
received significant notice due to its low cost, non-toxicity, air
and water compatibility, ease of handling, greater selectivity,
recyclability, enhanced reaction rates, experimental simplicity
and ease of preparation.17a
smoothly and gave the product 4a in 94% yield (Table 1, entry
16). Moreover, we found that the yields were obviously affected
by the amount of STA loaded. When 5 mol%, 10 mol% and 20
mol% of STA were used the yields were 85, 94 and 93%,
respectively (Table 1, entries 16-18). Therefore, 10 mol% of
STA was sufficient and optimal quantity for the completion of
the reaction.
Table 1 Optimization of reaction conditions for the synthesis
of pyrano[3,2-c]chromen-5-ones (4a)a.
As part of our ongoing research program on the development
of clean protocols as well as our interest in applications of silica-
supported catalysts19-25 in organic reactions, herein, we report a
green and convenient protocol for the synthesis of pyrano[3,2-
c]chromen-5-ones via a multicomponent reaction of a 4-
hydroxycoumarin, aldehydes and (E)-N-methyl-1-(methylthio)-
2- nitroethenamine in the presence of catalytic amount of STA in
solvent-free condition with excellent yields (Scheme 1).
Entry Catalyst (mol Solvent Temp Time
Yield
(%)b
%)
(0C)
80
1
2
3
4
5
-
EtOH
EtOH
EtOH
EtOH
EtOH
18 h
8 h
8 h
7 h
5 h
-
TSA (10%)
GSA (10%)
PSA (10%)
80
38
42
29
52
80
80
Scheme 1. Synthesis of pyrano[3,2-c]chromen-5-ones
derivative catalyzed by STA under solvent free conditions.
CAN.SiO2
(10%)
80
6
7
FeCl3.SiO2
(10%)
EtOH
EtOH
80
80
6 h
6 h
56
45
2. Results and discussion
For our initial investigation, the reaction of 4-
hydroxycoumarin (1, 1 mmol), 4-methoxybenzaldehyde (2a, 1
mmol) and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (3, 1
mmol) was chosen as a model reaction to optimize the reaction
conditions at 80 °C. The results are summarized in Table 1. The
reaction was first carried out in ethanol in the absence and
presence of several acid catalysts. The reaction did not proceed
even after prolonged reaction time (18 hours) and no desired
product was formed in the absence of catalyst at 80 °C in ethanol
(Table 1, entry 1). After that, the model reaction was performed
in the presence of 10 mol% of the tungstate sulfuric acid (TSA)
in ethanol at 80 °C. The reaction provided the corresponding title
product 4a, which was isolated in 38% product yield (Table 1,
entry 2) after 8 h. The product 4a was confirmed by usual
spectroscopic techniques. Therefore, our efforts focused on the
search for a suitable catalyst, such as glucose sulfonic acid
(GSA), phospho sulfonic acid (PSA), CAN.SiO2, FeCl3.SiO2,
ZnCl2.SiO2, p-TSA and STA can catalyze this reaction at 80 °C
in ethanol (Table 1, entries 3–9). Among all the screened
catalysts, STA was found superior for the desired product in
MCR reaction, with these merits, like reaction time, product
yield (Table 1, entry 9).
ZnCl2.SiO2
(10%)
8
p-TSA (10%) EtOH
80
80
3 h
2 h
78
88
54
60
46
-
9
STA (10%)
STA (10%)
STA (10%)
STA (10%)
STA (10%)
STA (10%)
STA (10%)
STA (10%)
STA (5%)
EtOH
CH2Cl2
DMF
THF
10
11
12
13
14
15
16
17
18
reflux 4 h
120 3 h
reflux 4 h
H2O
reflux
6 h
4 h
4 h
CH3CN reflux
Toluene reflux
65
52
Neat
Neat
Neat
80
80
80
20 min 94
40 min 85
STA (20%)
20 min
93
aReaction of 4-hydroxycoumarin (1, 1 mmol), 4-methoxy
benzaldehyde (2a, 1 mmol) and (E)-N-methyl-1-(methylthio)-2-
nitroethenamine (3, 1 mmol), STA (10 mol%) with solvent (5
mL) or solvent-free conditions. bIsolated yield.
In addition, we investigated the influence of various organic
solvents such as CH2Cl2, DMF, THF, H2O, CH3CN, and Toluene
at different reaction temperatures on the model reaction with 10
mol% of STA (Table 1, entry 10-15). In these cases, product 4a
was formed in slightly lower yields. With respect to the solvent
system, the best results were achieved using ethanol (Table 1,
entry 9). In recent years, the syntheses of compounds under
solvent-free conditions is an important task in heterocyclic
synthesis, because such reactions are environmentally friendly,
cost-effective and have easy workup procedures, fast reaction
rates, and high yields.26 Therefore, we decided to test a solvent-
free version with STA catalyst (Table 1, entries 16–18). Most
The reaction was studied at different temperatures to find out
the optimum reaction temperature for the preparation of 4a in the
presence of 10 mol% of STA under solvent free condition (Table
2). It was observed that the reaction did not proceed at room
temperature, but in 40 °C reaction gives trace of product (Table
2, entry 2). The reaction proceeds smoothly at 60 °C but the
yield of the product is not acceptable. On the other hand the
reaction at 80 oC proceeded very effectively, with excellent
yields (Table 2, entry 4). Further increase of temperature the

3
product yield was not increased. Therefore, the best reaction
conditions were obtained by using 10 mol % of STA as the
catalyst under solvent free condition at 80 °C to afford the
desired product 4a in 94% yield within 20 min (Table 2, entry 4).
mol% of the STA catalyst. Therefore, the present protocol has
ACCEPTED MANUSCRIPT
general applicability and accommodates a variety of substitution
patterns.
Table 2: Temperature effect on the preparation of
pyrano[3,2-c]chromen-5-onesa.
A variety of substrates were submitted to the optimum
reaction conditions and the desired products were obtained in
excellent yields (Table 3). Various functional groups substituted
at the aromatic ring of the aldehyde substrate, including electron
withdrawing groups such as bromo, chloro, fluoro and nitro
(Table 3, entries 4e-4h, 4j, 4o, 4p-4t and 4v) and electron
donating groups such as methyl, methoxy, ethoxy, and 4-N,N-
dimethylamino (Table 3, entries 4a-4d, 4i, 4l, 4m and 4w). In
addition, heteroaryl aldehydes also participate in the
multicomponent reaction to produce the desired products in good
yields without affecting the heterocyclic moieties (Table 3,
entries 4x-4z). In general, the reactions were clean and no side
products were detected. In all cases, the reactions proceeded
efficiently at 80 ºC under solvent free conditions and with 10
Entry
Temp (oC)
Time (min)
Yield (%)b
1
2
3
4
5
Room temp
120
55
-
40
traces
65
60
45
80
20
94
100
20
93
aReaction of 4-hydroxycoumarin (1, 1 mmol), benzaldehyde
(2a, mmol) and (E)-N-methyl-1-(methylthio)-2-
nitroethenamine (3, 1 mmol) catalyzed by STA (10 mol%)
1
under solvent free condition. bIsolated yield.
Table 3 STA catalyzed multicomponent synthesis of pyrano[3,2-c]chromen-5-ones under solvent-free conditionsa.
Entry
R
Product
Time (min)
Yield (%)b
M.p (°C)
1
4-OMe-C6H4
4-OC2H5-C6H4
4-CH3-C6H4
3,4,5-OMe-C6H2
3-Cl-C6H4
4a
4b
4c
4d
4e
4f
20
20
20
22
30
35
32
36
20
30
20
22
20
35
40
38
36
35
37
40
35
36
30
32
30
35
94
89
94
90
87
89
85
86
90
87
94
92
89
88
86
89
85
88
90
87
86
90
89
87
90
88
259-261
260-262
258-260
266-268
256-258
265-267
267-269
265-267
267-269
269-271
270-272
265-267
271-273
272-274
263-265
252-254
265-267
284-286
282-284
245-247
258-260
247-249
253-255
226-228
265-267
266-268
2
3
4
5
6
4-F-C6H4
7
4-NO2-C6H4
4-Br-C6H4
4g
4h
4i
8
9
3-OMe-C6H4
2-NO2-C6H4
C6H5
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
4j
4k
4l
2,5-OMe-C6H3
2-OMe-C6H4
1-Napthaldehyde
3-F-C6H4
4m
4n
4o
4p
4q
4r
4s
4-Cl-C6H4
3-NO2-C6H4
2-Br-C6H4
2-Cl,5-Br-C6H3
2-OH,3-Br,5-Cl-C6H2
2,3-OH-C6H3
2-OH,3,5-Cl-C6H2
4-N,N-Methyl- C6H4
Pyridin-4-yl
Furan-2-yl
4t
4u
4v
4w
4x
4y
4z
Thiophene-2-yl
aReaction of 4-hydroxycoumarin (1, 1 mmol), benzaldehyde (2a-2z, 1 mmol) and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (3,
1 mmol) (3, mmol) catalyzed by STA (10 mol%) under solvent free. bIsolated yield.

4
Tetrahedron
ACCEPTED MANUSCRIPT
All the structure of synthesized compounds (4a-4z) have
advantages of this method over other existing ones are reduced
been ascertained on the basis of H NMR, 13C NMR, IR and
HRMS data.
reaction times, excellent yields, simple experimental procedure,
low cost, easy handling, and economic viability of the catalyst.
The procedures provide access to compounds that are useful in
heterocyclic synthesis.
1
The reusability of catalysts is an important factor for
commercial uses. The reusability of the catalyst was also
examined in the synthesis of 4a (pyrano[3,2-c]chromen-5-ones).
The catalyst was easily recovered after each run from the
reaction medium, washed with ethyl acetate and acetone, dried
under vacuum at 120 °C and tested for its activity in subsequent
runs. It was found that the catalyst could be reused four times
without loss of activity (Table 4, entry 1–4).
4. Experimental
4.1 Material and methods
Chemicals were purchased from Aldrich and Alfa Aesar
Chemical Companies and used without further purification.
NMR spectra were recorded in parts per million (ppm) in
DMSO-d6 on a Jeol JNM ECP 600 NMR instrument using TMS
as internal standard. Standard abbreviations were used to denote
signal multiplicities (s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet). Mass spectra were recorded on a Jeol
JMS-700 mass spectrometer. The IR spectra were recorded on a
perkin elmer (U.S.A), spectrum X instrument. All melting points
were determined using open capillaries on an Electrothermal-
9100 (Japan) instrument and are uncorrected.
Table 4: A study of the reusability of STA in the model
reactiona
Entry
Reaction cycle
First (fresh run)
Second cycle
Third cycle
Yield (%)b
1
2
3
4
94
92
88
88
Fourth cycle
4.2 Synthesis of 4-(4-methoxyphenyl) -2-(methylamino) -3-
aModel reaction run with 4-hydroxycoumarin (1, 1 mmol), 4-
methoxybenzaldehyde (2a, mmol) and (E)-N-methyl-1-
nitro-4H,5H-pyrano [3,2-c]chromen-5-one (4a).
1
A
mixture of 4-hydroxycoumarin (1,
1
mmol), 4-
(methylthio)-2-nitroethenamine (3, 1 mmol), STA (10 mol%)
methoxybenzaldehyde (2a, mmol), (E)-N-methyl-1-
1
b
under solvent-free conditions. Isolated yield.
(methylthio)-2-nitroethenamine (3, 1 mmol) and silica-supported
tungstic acid (STA) (10 mol %) was stirred at 80 oC under
solvent-free conditions. The progress of the reaction was
monitored by TLC. After completion of the reaction, the reaction
mixture was washed with ethanol. The residue dissolved in
DCM, and the insoluble STA was separated by simple filtration
and washed with DCM. The solvent was evaporated under
reduced pressure and the obtained crude was recrystallized from
ethanol to afford the pure yellow product 4a. The recovered
catalyst was washed with ethyl acetate and acetone, dried and
reused. Compounds 4b-4z were also synthesized by adopting
this procedure.
The possible reaction sequences taking place in the synthesis
of pyrano[3,2-c]chromen-5-ones derivatives (4a-4z) is shown in
(Figure 2). The first step is the Knoevenagel condensation
between 4-hydroxycoumarin 1 and aldehyde 2 in the presence of
STA afforded intermediate 5, which acts as Michael acceptor.
The adduct 5 immediately undergoes Michael type addition with
(E)-N-methyl-1-(methylthio)-2-nitroethenamine 3 to affords the
iminol 6. This iminol 6 apparently tautomerizes to aminol 7
followed by intramolecular O-cyclization to give the pyrano[3,2-
c]chromen-5-ones derivatives (4a-4z) in good yield through the
elimination of MeSH.
4.2.1. 4-(4-methoxyphenyl) -2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4a). Yield 94%; yellow solid; Mp:
259-261 oC; IR (νmax) cm-1: 3211 (N-Hstr), 2941 & 2854 (C-Hstr),
1722 ( C=Ostr), 1265 & 1121 (C-Ostr), 1640 & 1435 (C=Cstr),
1013 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.38 (d, J =
5.0 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.75 – 7.72 (m, 1H), 7.50
(dd, J = 16.4, 8.0 Hz, 2H), 7.23 (d, J = 8.7 Hz, 2H), 6.81 (d, J =
8.7 Hz, 2H), 5.02 (s, 1H), 3.69 (s, 3H), 3.31 (d, J = 4.9 Hz, 3H),
13C NMR (151 MHz, DMSO-d6) δ 159.25, 158.31, 156.76,
151.99, 151.67, 133.28, 133.14, 129.57, 125.05, 122.84, 116.63,
113.49, 112.68, 107.99, 106.90, 55.06, 36.62, 28.73; HRMS
(ESI, m/z): calcd for C20H16N2O6 (M+H+) 380.1008, found:
380.1010.
4.2.2.
4-(4-ethoxyphenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4b). Yield 89%; yellow solid;
o
Mp: 260-262 C; IR (νmax) cm-1: 3220 (N-Hstr), 2935 & 2812 (C-
Hstr), 1700 ( C=Ostr), 1236 & 1102 (C-Ostr), 1632 & 1404
(C=Cstr), 1018 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ
10.36 (d, J = 5.1 Hz, 1H), 7.98 (d, J = 7.9 Hz, 1H), 7.51 – 7.45
(m, 2H), 7.21 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.7 Hz, 2H), 5.01
(s, 1H), 3.94 (q, J = 7.0 Hz, 2H), 3.31 (d, J = 4.8 Hz, 3H), 1.27
(dd, J = 7.3, 6.7 Hz, 3H), 13C NMR (151 MHz, DMSO-d6) δ
159.19, 157.57, 156.75, 151.95, 151.63, 133.08, 129.47, 124.99,
122.77, 116.57, 113.93, 112.64, 107.97, 106.90, 62.96, 36.55,
28.66, 14.62; HRMS (ESI, m/z): calcd for C21H18N2O6 (M+H+)
394.1165, found: 394.1166.
Figure 2: Possible Mechanism for the synthesis of pyrano[3,2-c]chromen-5-
ones derivatives
3. Conclusion
In conclusion, we demonstrated a facile and environmentally
benign method for the synthesis of highly functionalized
pyrano[3,2-c]chromen-5-ones by a one-pot three-component
condensation reaction of 4-hydroxycoumarin, aldehydes, and (E)
-N-methyl-1-(methylthio)-2-nitroethenamine in the presence of
an inexpensive and reusable silica-supported tungstic acid (STA)
as a heterogeneous catalyst under solvent-free conditions. The

5
4.2.3. 2-(methylamino)-3-nitro-4-(p-tolyl)-4H,5H-pyrano[3,2-
c]chromen-5-one (4c). Yield 94%; yellow solid; Mp: 258-260
oC; IR (νmax) cm-1: 3196 (N-Hstr), 2988 & 2836 (C-Hstr), 1712 (
C=Ostr), 1289 & 1095 (C-Ostr), 1628 & 1410 (C=Cstr), 1014 (C-
1735 ( C=Ostr), 1254 & 1121 (C-Ostr), 1617 & 1410 (C=Cstr),
ACCEPTED MANUSCRIPT
1021 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.40 (d, J =
5.1 Hz, 1H), 8.01 (dd, J = 7.9, 1.4 Hz, 1H), 7.76 – 7.73 (m, 1H),
7.53 – 7.48 (m, 2H), 7.46 – 7.44 (m, 2H), 7.33 – 7.31 (m, 2H),
5.05 (s, 1H), 3.32 (d, J = 4.9 Hz, 3H), 13C NMR (151 MHz,
DMSO-d6) δ 159.18, 156.66, 152.01, 140.64, 133.25, 130.85,
125.03, 122.90, 120.16, 116.62, 112.58, 107.40, 106.01, 37.18,
28.71; HRMS (ESI, m/z): calcd for C19H13BrN2O5 (M+H+)
428.0008, found: 428.0010.
1
O-Cstr); H NMR (600 MHz, DMSO-d6) δ 10.38 (d, J = 5.1 Hz,
1H), 7.99 (dd, J = 7.9, 1.5 Hz, 1H), 7.74 – 7.70 (m, 1H), 7.51 –
7.46 (m, 2H), 7.20 (d, J = 8.1 Hz, 2H), 7.06 (d, J = 7.9 Hz, 2H),
5.03 (s, 1H), 3.31 (d, J = 5.0 Hz, 3H), 2.22 (s, 3H), 13C NMR
(151 MHz, DMSO-d6) δ 159.15, 156.75, 151.96, 151.72, 138.28,
136.24, 133.09, 128.62, 128.30, 124.98, 122.78, 116.56, 112.61,
107.86, 106.80, 36.99, 28.66, 20.58; HRMS (ESI, m/z): calcd for
C20H16N2O5 (M+H+) 364.1059, found: 364.1059.
4.2.9. 4-(3-methoxyphenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4i). Yield 90%; yellow solid; Mp:
267-269 oC; IR (νmax) cm-1: 3201 (N-Hstr), 2957 & 2833 (C-Hstr),
1702 ( C=Ostr), 1265 & 1145 (C-Ostr), 1606 & 1430 (C=Cstr),
1039 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.38 (d, J =
4.9 Hz, 1H), 8.01 (d, J = 7.9 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H),
7.51 (dd, J = 15.9, 8.1 Hz, 2H), 7.20 – 7.17 (m, 1H), 6.87 (dd, J
= 4.5, 1.8 Hz, 2H), 6.80 – 6.78 (m, 1H), 5.08 (s, 1H), 3.71 (s,
3H), 3.32 (d, 3H), 13C NMR (151 MHz, DMSO-d6) δ 159.22,
158.93, 156.82, 151.98, 142.70, 133.17, 129.21, 125.01, 122.85,
120.40, 116.60, 115.12, 112.64, 111.78, 107.63, 106.57, 54.98,
037.32, 28.69; HRMS (ESI, m/z): calcd for C20H16N2O6 (M+H+)
380.1008, found: 380.1010.
4.2.4.
2-(methylamino)-3-nitro-4-(3,4,5-trimethoxyphenyl)-
4H,5H-pyrano[3,2-c]chromen-5-one (4d). Yield 90%; yellow
o
solid; Mp: 266-268 C; IR (νmax) cm-1: 3224 (N-Hstr), 2952 &
2851 (C-Hstr), 1698 ( C=Ostr), 1273 & 1114 (C-Ostr), 1636 &
1
1430 (C=Cstr), 1025 (C-O-Cstr); H NMR (600 MHz, DMSO-d6)
δ 10.38 (d, J = 5.1 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.74 – 7.71
(m, 1H), 7.49 (dd, J = 14.9, 7.9 Hz, 2H), 6.57 (s, 2H), 5.08 (s,
1H), 3.71 (s, 6H), 3.60 (s, 3H), 3.32 (d, J = 5.0 Hz, 3H), 13C
NMR (151 MHz, DMSO-d6) δ 159.33, 156.92, 152.54, 152.03,
136.91, 136.70, 133.12, 124.95, 122.89, 116.58, 112.72, 107.48,
106.46, 106.01, 59.90, 56.00, 37.56, 28.72; HRMS (ESI, m/z):
calcd for C22H20N2O8 (M+H+) 440.1220, found: 440.1222.
4.2.10.
2-(methylamino)-3-nitro-4-(2-nitrophenyl)-4H,5H-
pyrano[3,2-c]chromen-5-one (4j). Yield 87%; yellow solid; Mp:
269-271 oC; IR (νmax) cm-1: 3213 (N-Hstr), 2938 & 2862 (C-Hstr),
1690 ( C=Ostr), 1290 & 1106 (C-Ostr), 1634 & 1426 (C=Cstr),
1012 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.49 (d, J =
4.9 Hz, 1H), 8.03 (d, J = 7.9 Hz, 1H), 7.91 (d, J = 8.0 Hz, 1H),
7.78 – 7.74 (m, 1H), 7.58 (d, J = 6.2 Hz, 2H), 7.54 – 7.49 (m,
2H), 7.47 – 7.44 (m, 1H), 6.07 (s, 1H), 3.32 (s, 3H); 13C NMR
(151 MHz, DMSO-d6) δ 157.11, 153.03, 152.65, 150.12, 133.96,
133.75, 128.81, 125.58, 124.75, 123.56, 117.15, 112.98, 107.78,
105.69, 79.71, 40.07, 33.27, 29.29; HRMS (ESI, m/z): calcd for
C20H16N2O6 (M+H+) 395.0753, found: 395.0755.
4.2.5.
4-(3-chlorophenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4e). Yield 87%; yellow solid; Mp:
256-258 oC; IR (νmax) cm-1: 3188 (N-Hstr), 2978 & 2834 (C-Hstr),
1731 ( C=Ostr), 1242 & 1125 (C-Ostr), 1606 & 1426 (C=Cstr),
1028 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.42 (d, J =
5.1 Hz, 1H), 8.00 (dd, J = 7.9, 1.4 Hz, 1H), 7.75 – 7.72 (m, 1H),
7.52 – 7.47 (m, 2H), 7.40 (t, J = 1.6 Hz, 1H), 7.30 (ddt, J = 13.9,
6.5, 1.7 Hz, 3H), 5.06 (s, 1H), 3.32 (d, J = 5.0 Hz, 3H),13C NMR
(151 MHz, DMSO-d6) δ 159.19, 156.65, 152.07, 143.57, 133.27,
132.58, 129.85, 128.46, 127.36, 127.12, 125.01, 122.93, 116.60,
112.58, 107.27, 105.77, 37.48, 28.73; HRMS (ESI, m/z): calcd
for C19H13ClN2O5 (M+H+) 384.0513, found: 384.0515.
4.2.11. 2-(methylamino)-3-nitro-4-phenyl-4H,5H-pyrano[3,2-
c]chromen-5-one (4k). Yield 94%; yellow solid; Mp: 270-272
oC; IR (νmax) cm-1: 3203 (N-Hstr), 2968 & 2818 (C-Hstr), 1715 (
C=Ostr), 1281 & 1142 (C-Ostr), 1646 & 1420 (C=Cstr), 1037 (C-
4.2.6.
4-(4-fluorophenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4f). Yield 89%; yellow solid; Mp:
265-267 oC; IR (νmax) cm-1: 3208 (N-Hstr), 2950 & 2816 (C-Hstr),
1707 ( C=Ostr), 1240 & 1118 (C-Ostr), 1652 & 1458 (C=Cstr),
1042 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.39 (d, J =
5.0 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.74 – 7.71 (m, 1H), 7.52
– 7.46 (m, 2H), 7.38 (dd, J = 8.4, 5.5 Hz, 2H), 7.07 (t, J = 8.8
Hz, 2H), 5.07 (s, 1H), 3.32 (d, J = 4.9 Hz, 3H), 13C NMR (151
MHz, DMSO-d6) δ 161.97, 160.35, 159.17, 156.68, 152.02,
151.87, 137.38, 133.19, 130.46, 125.01, 122.85, 116.59, 114.84,
114.74, 112.59, 107.66, 106.36, 36.85, 28.69; HRMS (ESI, m/z):
calcd for C19H13FN2O5 (M+H+) 368.0808, found: 368.0808.
1
O-Cstr); H NMR (600 MHz, DMSO-d6) δ 10.39 (d, J = 5.1 Hz,
1H), 8.01 (dd, J = 7.9, 1.5 Hz, 1H), 7.75 – 7.72 (m, 1H), 7.53 –
7.48 (m, 2H), 7.34 (dd, J = 5.2, 3.4 Hz, 2H), 7.27 (dd, J = 10.3,
4.9 Hz, 2H), 7.21 – 7.18 (m, 1H), 5.09 (s, 1H), 3.32 (d, J = 5.0
Hz, 3H), 13C NMR (151 MHz, DMSO-d6) δ 159.19, 156.80,
151.94, 141.25, 133.16, 128.45, 128.06, 127.05, 125.01, 122.84,
116.60, 112.63, 107.81, 106.69, 37.43, 28.68; HRMS (ESI, m/z):
calcd for C19H14N2O5 (M+H+) 350.0903, found: 350.0905.
4.2.12.
4-(2,5-dimethoxyphenyl)-2-(methylamino)-3-nitro-
4H,5H-pyrano[3,2-c]chromen-5-one (4l). Yield 92%; yellow
o
4.2.7.
2-(methylamino)-3-nitro-4-(4-nitrophenyl)-4H,5H-
solid; Mp: 265-267 C; IR (νmax) cm-1: 3197 (N-Hstr), 2947 &
pyrano[3,2-c]chromen-5-one (4g). Yield 85%; yellow solid; Mp:
267-269 oC; IR (νmax) cm-1: 3211 (N-Hstr), 2994 & 2835 (C-Hstr),
1745 ( C=Ostr), 1285 & 1130 (C-Ostr), 1643 & 1428 (C=Cstr),
1009 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.45 (d, J =
5.0 Hz, 1H), 8.13 – 8.11 (m, 2H), 8.03 (dd, J = 7.9, 1.3 Hz, 1H),
7.77 – 7.74 (m, 1H), 7.68 – 7.66 (m, 2H), 7.54 – 7.49 (m, 2H),
5.20 (s, 1H), 3.33 (d, 3H), 13C NMR (151 MHz, DMSO-d6) δ
159.18, 156.59, 152.30, 152.14, 148.71, 146.51, 133.43, 130.11,
125.09, 123.04, 116.66, 112.52, 107.02, 105.28, 37.77, 28.78;
HRMS (ESI, m/z): calcd for C19H13N3O7 (M+H+) 395.0753,
found: 395.0753.
2834 (C-Hstr), 1730 ( C=Ostr), 1275 & 1095 (C-Ostr), 1648 &
1408 (C=Cstr), 1019 (C-O-Cstr); H NMR (600 MHz, DMSO-d6)
1
δ 10.43 (d, J = 5.1 Hz, 1H), 8.03 (dd, J = 7.9, 1.5 Hz, 1H), 7.74 –
7.71 (m, 1H), 7.50 (ddd, J = 17.1, 8.6, 0.8 Hz, 2H), 6.95 (d, J =
3.1 Hz, 1H), 6.82 (d, J = 8.9 Hz, 1H), 6.78 (dd, J = 8.9, 3.1 Hz,
1H), 5.00 (s, 1H), 3.71 (s, 3H), 3.53 (s, 3H), 3.34 (d, J = 5.1 Hz,
3H), 13C NMR (151 MHz, DMSO-d6) δ 159.17, 157.61, 152.48,
152.13, 151.92, 132.98, 128.02, 125.01, 122.56, 119.40, 116.59,
112.78, 112.52, 106.45, 104.34, 56.03, 55.36, 36.04, 28.48;
HRMS (ESI, m/z): calcd for C21H18N2O7 (M+H+) 410.1114,
found: 410.1115.
4.2.8.
4-(4-bromophenyl)-2-(methylamino)-3-nitro-4H,5H-
4.2.13. 4-(2-methoxyphenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4h). Yield 86%; yellow solid; Mp:
pyrano[3,2-c]chromen-5-one (4m). Yield 89%; yellow solid;
o
265-267 oC; IR (νmax) cm-1: 3184 (N-Hstr), 2932 & 2858 (C-Hstr),
Mp: 271-273 C; IR (νmax) cm-1: 3215 (N-Hstr), 2964 & 2844 (C-

6
Tetrahedron
Hstr), 1699 ( C=Ostr), 1250 & 1113 (C-Ost ), 1634 & 1417
4.2.18. 4-(2-bromophenyl)-2-(methylamino)-3-nitro-4H,5H-
ACCEPTED MANUSCRIPT
r
(C=Cstr), 1026 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ
10.43 (d, J = 5.1 Hz, 1H), 8.04 (dd, J = 7.9, 1.5 Hz, 1H), 7.74 –
7.71 (m, 1H), 7.53 – 7.47 (m, 2H), 7.40 (dd, J = 7.9, 1.7 Hz, 1H),
7.21 – 7.18 (m, 1H), 6.91 (dd, J = 10.7, 4.4 Hz, 2H), 5.08 (s,
1H), 3.60 (s, 3H), 3.35 (d, J = 5.1 Hz, 3H), 13C NMR (151 MHz,
DMSO-d6) δ 159.19, 157.65, 152.17, 151.94, 132.94, 128.60,
126.82, 125.00, 122.56, 119.79, 116.59, 112.60, 111.85, 106.55,
104.53, 79.15, 55.46, 35.88, 28.49; HRMS (ESI, m/z): calcd for
C20H16N2O6 (M+H+) 380.1008, found: 380.1008.
pyrano[3,2-c]chromen-5-one (4r) Yield 88%; yellow solid;
Mp: 284-286 C; IR (νmax) cm-1: 3202 (N-Hstr), 2923 & 2862 (C-
o
Hstr), 1728 ( C=Ostr), 1252 & 1120 (C-Ostr), 1625 & 1450
(C=Cstr), 1029 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ
10.46 (d, J = 5.0 Hz, 1H), 8.03 (d, J = 7.9 Hz, 1H), 7.75 (t, J =
7.8 Hz, 1H), 7.54 – 7.48 (m, 4H), 7.29 (t, J = 7.5 Hz, 1H), 7.15 –
7.12 (m, 1H), 5.40 (s, 1H), 3.34 (d, J = 5.0 Hz, 3H), 13C NMR
(151 MHz, DMSO- d6) δ 158.84, 156.79, 152.08, 133.34,
132.87, 128.86, 127.23, 125.02, 122.97, 116.59, 115.78, 112.35,
28.67; HRMS (ESI, m/z): calcd for C19H13BrN2O5 (M+H+)
428.0008, found: 428.0008.
4.2.14. 2-(methylamino)-4-(naphthalen-1-yl)-3-nitro-4a,10b-
dihydro-4H,5H-pyrano[3,2-c]chromen-5-one (4n). Yield 88%;
yellow solid; Mp: 272-274 C; IR (νmax) cm-1: 3206 (N-Hstr),
4.2.19. 4-(2-bromo-6-chlorophenyl)-2-(methylamino)-3-nitro-
o
2924 & 2830 (C-Hstr), 1720 ( C=Ostr), 1260 & 1130 (C-Ostr),
1620 & 1439 (C=Cstr), 1009 (C-O-Cstr); H NMR (600 MHz,
4H,5H-pyrano[3,2-c]chromen-5-one (4s). Yield 90%; yellow
1
o
solid; Mp: 282-284 C; IR (νmax) cm-1: 3208 (N-Hstr), 2947 &
DMSO-d6) δ 10.41 (s, 1H), 8.70 (d, J = 8.6 Hz, 1H), 8.07 (dd, J
= 8.0, 1.5 Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.79 – 7.72 (m, 2H),
7.62 (ddd, J = 8.4, 6.9, 1.2 Hz, 1H), 7.55 – 7.51 (m, 2H), 7.47 (d,
J = 8.2 Hz, 1H), 7.39 – 7.36 (m, 2H), 6.02 (s, 1H), 3.37 (d, J =
5.0 Hz, 3H), 13C NMR (151 MHz, DMSO-d6) δ 159.28, 156.74,
152.93, 151.76, 150.94, 143.51, 133.19, 132.90, 132.78, 131.80,
129.71, 127.93, 127.59, 125.65, 125.46, 124.98, 122.86, 116.58,
112.68, 109.21, 83.82, 37.24, 28.72; HRMS (ESI, m/z): calcd for
C23H18N2O5 (M+H+) 402.1216, found: 402.1214.
2820 (C-Hstr), 1740 ( C=Ostr), 1242 & 1140 (C-Ostr), 1624 &
1412 (C=Cstr), 1010 (C-O-Cstr); H NMR (600 MHz, DMSO-d6)
1
δ 10.46 (d, J = 5.1 Hz, 1H), 8.31 (s, 1H), 8.02 (dd, J = 7.9, 1.5
Hz, 1H), 7.77 – 7.74 (m, 1H), 7.60 (dd, J = 6.7, 2.5 Hz, 1H),
7.54 – 7.49 (m, 2H), 7.09 (dd, J = 10.2, 8.8 Hz, 1H), 5.23 (s,
1H), 3.33 (s, 3H), 13C NMR (151 MHz, DMSO-d6) δ 160.93,
159.17, 158.99, 158.93, 156.69, 152.32, 152.11, 133.37, 131.85,
125.05, 122.92, 117.61, 117.45, 116.66, 115.69, 112.43, 106.30,
104.28, 79.15, 32.56, 28.70; HRMS (ESI, m/z): calcd for
C19H12BrClN2O5 (M+H+) 461.9618, found: 461.9620.
4.2.15. 4-(3-fluorophenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4o). Yield 86%; yellow solid; Mp:
263-265 oC; IR (νmax) cm-1: 3186 (N-Hstr), 2916 & 2822 (C-Hstr),
1724 ( C=Ostr), 1269 & 1124 (C-Ostr), 1616 & 1416 (C=Cstr),
1041 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.40 (s, 1H),
8.00 (d, J = 1.0 Hz, 1H), 7.75 (d, J = 15.4 Hz, 1H), 7.51 (dd, J =
8.6, 2.5 Hz, 2H), 7.31 (dd, J = 13.3, 6.0 Hz, 1H), 7.19 (d, J = 8.7
Hz, 2H), 7.03 (d, J = 8.0 Hz, 1H), 5.10 (s, 1H), 3.32 (s, 3H), 13C
NMR (151 MHz, DMSO-d6) δ 161.07, 159.20, 156.69, 152.06,
143.95, 133.25, 129.78, 125.01, 124.65, 122.93, 116.61, 115.51,
115.37, 114.18, 114.02, 113.92, 112.61, 107.34, 105.93, 37.39,
28.71; HRMS (ESI, m/z): calcd for C23H18N2O5 (M+H+)
368.0808, found: 368.0808.
4.2.20.
4-(3-bromo-6-chloro-2-hydroxyphenyl)-2-
(methylamino)-3-nitro-4H,5H-pyrano[3,2-c]chromen-5-one (4t).
Yield 87%; yellow solid; Mp: 245-247 C; IR (νmax) cm-1: 3228
o
(N-Hstr), 2962 & 2826 (C-Hstr), 1698 ( C=Ostr), 1292 & 1122 (C-
Ostr), 1651 & 1420 (C=Cstr), 1014 (C-O-Cstr); H NMR (600
1
MHz, DMSO-d6) δ 12.31 (s, 1H), 10.45 (d, J = 5.1 Hz, 1H), 8.03
(dd, J = 8.0, 0.8 Hz, 1H), 7.86 (d, J = 2.3 Hz, 1H), 7.63 – 7.60
(m, 1H), 7.37 (dd, J = 11.4, 4.0 Hz, 1H), 7.34 – 7.31 (m, 2H),
5.94 (s, 1H), 3.21 (d, J = 5.0 Hz, 3H), 13C NMR (151 MHz,
DMSO-d6) δ 160.98, 158.87, 152.08, 146.30, 135.79, 133.57,
132.32, 129.98, 124.05, 116.70, 116.25, 116.08, 110.42, 31.92,
28.44; HRMS (ESI, m/z): calcd for C17H12BrClN2O6 (M+H+)
477.9567, found: 477.9567.
4.2.16. 4-(4-chlorophenyl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4p). Yield 89%; yellow solid; Mp:
252-254 oC; IR (νmax) cm-1: 3220 (N-Hstr), 2923 & 2840 (C-Hstr),
1688 ( C=Ostr), 1245 & 1140 (C-Ostr), 1642 & 1429 (C=Cstr),
1056 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.40 (d, J =
5.1 Hz, 1H), 8.01 (dd, J = 7.9, 1.4 Hz, 1H), 7.76 – 7.73 (m, 1H),
7.51 (dd, J = 8.7, 1.3 Hz, 2H), 7.39 – 7.37 (m, 2H), 7.32 – 7.30
(m, 2H), 5.07 (s, 1H), 3.32 (d, J = 5.0 Hz, 3H), 13C NMR (151
MHz, DMSO-d6) δ 159.18, 156.67, 152.05, 140.21, 133.23,
131.63, 130.45, 127.94, 125.03, 122.89, 116.62, 106.14, 100.80,
32.47, 28.71; HRMS (ESI, m/z): calcd for C19H13ClN2O5 (M+H+)
384.0513, found: 384.0515.
4.2.21.
4-(2,3-dihydroxyphenyl)-2-(methylamino)-3-nitro-
4H,5H-pyrano[3,2-c]chromen-5-one (4u). Yield 86%; yellow
solid; Mp: 258-260 C; IR (νmax) cm-1: 3203 (N-Hstr), 2986 &
o
2843 (C-Hstr), 1714 ( C=Ostr), 1265 & 1108 (C-Ostr), 1618 &
1421 (C=Cstr), 1023 (C-O-Cstr); H NMR (600 MHz, DMSO-d6)
1
δ 12.05 (s, 1H), 10.55 (d, J = 5.1 Hz, 1H), 9.87 (s, 1H), 8.01 (d, J
= 7.5 Hz, 1H), 7.61 – 7.58 (m, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.32
(d, J = 8.2 Hz, 1H), 6.90 (t, J = 7.9 Hz, 1H), 6.80 (dd, J = 8.0,
1.3 Hz, 1H), 6.61 (d, J = 7.6 Hz, 1H), 5.87 (s, 1H), 3.19 (d, J =
5.1 Hz, 3H), 13C NMR (151 MHz, DMSO-d6) δ 160.18, 159.54,
151.95, 144.71, 137.09, 132.04, 125.01, 123.98, 117.89, 116.13,
115.15, 56.02, 31.75, 28.03; HRMS (ESI, m/z): calcd for
C19H14N2O7 (M+H+) 382.0801, found: 382.0803.
4.2.17.
2-(methylamino)-3-nitro-4-(3-nitrophenyl)-4H,5H-
pyrano[3,2-c]chromen-5-one (4q). Yield 85%; yellow solid; Mp:
265-267 oC; IR (νmax) cm-1: 3194 (N-Hstr), 2988 & 2856 (C-Hstr),
1701 ( C=Ostr), 1285 & 1115 (C-Ostr), 1641 & 1440 (C=Cstr),
1022 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ 10.46 (s, 1H),
8.17 (t, J = 2.0 Hz, 1H), 8.08 (ddd, J = 8.2, 2.2, 0.8 Hz, 1H), 8.04
(dd, J = 7.9, 1.4 Hz, 1H), 7.86 (dd, J = 7.9, 1.1 Hz, 1H), 7.77 –
7.74 (m, 1H), 7.58 – 7.49 (m, 3H), 5.21 (s, 1H), 3.34 (d, J = 5.0
Hz, 3H), 13C NMR (151 MHz, DMSO-d6) δ 159.25, 156.64,
152.31, 152.16, 147.45, 143.29, 135.42, 133.38, 129.49, 125.06,
123.30, 123.03, 122.17, 116.65, 112.56, 107.07, 105.30, 37.73,
28.78; HRMS (ESI, m/z): calcd for C19H13N3O7 (M+H+)
395.0753, found: 395.0755.
4.2.22. 4-(3,5-dichloro-2-hydroxyphenyl)-2-(methylamino)-3-
nitro-4H,5H-pyrano[3,2-c]chromen-5-one (4v). Yield 90%;
o
yellow solid; Mp: 247-249 C; IR (νmax) cm-1: 3186 (N-Hstr),
2957 & 2815 (C-Hstr), 1703 ( C=Ostr), 1236 & 1106 (C-Ostr),
1
1645 & 1409 (C=Cstr), 1025 (C-O-Cstr); H NMR (600 MHz,
DMSO-d6) δ 12.31 (s, 1H), 10.47 (d, J = 5.1 Hz, 1H), 8.03 (d, J
= 7.9 Hz, 1H), 7.66 (d, J = 2.4 Hz, 1H), 7.63 – 7.60 (m, 1H),
7.38 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.17 (d, J = 2.4
Hz, 1H), 5.93 (s, 1H), 3.20 (d, J = 5.1 Hz, 3H), 13C NMR (151
MHz, DMSO-d6) δ 160.99, 158.70, 152.08, 143.20, 132.32,
128.68, 128.22, 126.53, 126.51, 124.05, 121.14, 116.24, 116.06,
31.93, 28.26; HRMS (ESI, m/z): calcd for C19H12Cl2N2O6
(M+H+) 434.0072, found: 434.0072.

7
4. (a) Keivanloo, A.; Kazemi, S. S.; Nasr-Isfahani, H.; Bamoniri,
4.2.23.
4-(4-(dimethylamino)phenyl)-2-(methylamino)-3-
ACCEPTED MANUSCRIPT
A.; Tetrahedron 2016, 72, 6536-6542; (b) Hajduk, P. J.; Greer, J.
Nat. Rev. Drug Discovery 2007, 6, 211-219.
nitro-4H,5H-pyrano[3,2-c]chromen-5-one (4w). Yield 89%;
yellow solid; Mp: 253-255 C; IR (νmax) cm-1: 3223 (N-Hstr),
o
5. (a) Morteza, S. Chem. Rev. 2012, 112, 3508-3549; (b) Amol, B.
A.; Jeong, Y.T. Tetrahedron Lett. 2013, 54, 1302-1306.
6. (a) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199-2238;
(b) Wu, X. F.; Neumann, H.; Beller, M. Chem. Rev. 2013, 113, 1-
35.
7. (a) Huang, S. C.; Wu, P. L.; Wu, T. S. Phytochemistry 1997, 44,
179-181; (b) Mali, R. S.; Joshi, P. P.; Sandhu, P. K.; Manekar-
Tilve, A. J. Chem. Soc. Perkin Trans. 1 2002, 371-376; (c)
Arunrat, S.; Ngampong, K.; Boonsong, K.; Sida, P.; John, W. D.;
Thomas, F. S.; Yuth, N.; Sasarose, R. Planta Med. 2003, 69, 155-
157; (d) Boonsong, K.; Ngampong, K.; Arunrat, S.; Chanita, N.;
Chalobon, Y. Phytother. Res. 2005, 19, 728-731; (e) Su, C. R.;
Yeh, S. F.; Liu, C. M.; Damu, A. G.; Kuo, T. H.; Chiang, P. C.;
Bastow, K. F.; Lee, K. H.; Wu, T. S. Bioorg. Med. Chem. 2009,
17, 6137-6143.
2925 & 2837 (C-Hstr), 1718 ( C=Ostr), 1258 & 1121 (C-Ostr),
1640 & 1435 (C=Cstr), 1006 (C-O-Cstr); H NMR (600 MHz,
1
DMSO-d6) δ 10.34 (d, J = 5.1 Hz, 1H), 8.00 (dd, J = 7.9, 1.5 Hz,
1H), 7.74 – 7.71 (m, 1H), 7.52 – 7.48 (m, 2H), 7.10 (d, J = 8.8
Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 4.98 (s, 1H), 3.31 (d, J = 5.1
Hz, 3H), 2.82 (s, 6H), 13C NMR (151 MHz, DMSO-d6) δ 159.21,
156.81, 151.88, 151.41, 149.53, 132.95, 128.82, 124.96, 122.71,
116.56, 112.71, 112.04, 108.19, 107.27, 79.15, 36.25, 28.62;
HRMS (ESI, m/z): calcd for C21H12N3O5 (M+H+) 393.1325,
found: 395.1326.
4.2.24.
2-(methylamino)-3-nitro-4-(pyridin-4-yl)-4H,5H-
pyrano[3,2-c]chromen-5-one (4x). Yield 87%; yellow solid;
8. (a) Kalaria, P. N.; Satasia, S. P.; Raval, D. K. New J. Chem. 2014,
38, 1512-1521; (b) Zhang, G.; Zhang, Y.; Yan, J.; Chen, R.;
Wang, S.; Ma, Y.; Wang, R. J. Org. Chem. 2012, 77, 878-888; (c)
Mungra, D. C.; Patel, M. P.; Rajani, D. P.; Patel, R. G. Eur. J.
Med. Chem. 2011, 46, 4192-4200.
Mp: 226-228 C; IR (νmax) cm-1: 3214 (N-Hstr), 2994 & 2854 (C-
o
Hstr), 1697 ( C=Ostr), 1290 & 1145 (C-Ostr), 1644 & 1427
(C=Cstr), 1038 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ
10.45 (d, J = 4.0 Hz, 1H), 8.58 (d, J = 5.2 Hz, 1H), 8.50 (s, 1H),
8.02 (d, J = 7.9 Hz, 1H), 7.81 (d, J = 7.9 Hz, 1H), 7.76 (dd, J =
11.6, 4.1 Hz, 1H), 7.63 (d, J = 5.4 Hz, 1H), 7.51 (s, 1H), 7.25 (td,
J = 7.9, 1.3 Hz, 1H), 5.11 (s, 1H), 3.33 (d, J = 2.1 Hz, 3H), 13C
NMR (151 MHz, DMSO-d6) δ 159.19, 156.68, 155.68, 152.65,
152.47, 152.13, 148.49, 133.44, 131.47, 125.08, 124.21, 123.05,
119.44, 116.66, 115.68, 112.51, 79.15, 37.45, 28.77; HRMS
(ESI, m/z): calcd for C18H13N3O5 (M+H+) 351.0855, found:
351.0855.
9. Cingolani, G. M.; Gualtteri, F.; Pigin, M.; J. Med. Chem., 1961,
12, 531-532.
10. Wu, J. Y. C.; Fong, W. F.; Zhang, J. X.; Leung, C. H.; Kwong, H.
L.; Yang, M. S.; Li, D.; Cheung, H. Y.; Eur. J. Pharmacol., 2003,
473, 9-17.
11. Bonsignore, L.; Loy, G.; Secci D.; Calignano, A. Eur. J. Med.
Chem., 1993, 28, 517-520.
12. Perrella, F. W.; Chen, S. F.; Behrens, D. L.; Kaltenbach, R. F.;
Seitz, S. P. J. Med. Chem., 1994, 37, 2232-2237.
13. (a) Kashman, Y.; Gustafson, K. R.; Fuller, R. W.; Cardellina, J.
H.; McMahon, J. B.; Currens, M. J.; Buckheit, R. W.; Hughes, M.
J.; Gragg G. M.; Boyd, M. R. J. Med. Chem. 1992, 35, 2735-
2743; (b) Patil, A. D.; Freyer, A. J.; Eggleston, D. S.;
Waltiwanger, R. C.; Bean, M. F.; Taylor, P. B.; Caranfa, M. J.;
Breen, A. L.; Bartus, H. R.; Johnson, R. K.; Hertzberg, R. P.;
Westley J. W. J. Med. Chem. 1993, 36, 4131-4138.
14. Konkoy, C. S.; Fick, D. B.; Cai, S. X.; Lan N. C.; Keana, J. F. W.;
PCT Int. Appl. WO 0075123, 2000; Chem. Abstr. 2001, 134,
29313a.
4.2.25.
4-(furan-2-yl)-2-(methylamino)-3-nitro-4H,5H-
pyrano[3,2-c]chromen-5-one (4y). Yield 90%; yellow solid;
Mp: 265-267 C; IR (νmax) cm-1: 3210 (N-Hstr), 2918 & 2845 (C-
o
Hstr), 1710 ( C=Ostr), 1252 & 1104 (C-Ostr), 1635 & 1408
(C=Cstr), 1032 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ
10.35 (d, J = 4.9 Hz, 1H), 8.00 (d, J = 7.1 Hz, 1H), 7.78 – 7.75
(m, 1H), 7.54 – 7.51 (m, 2H), 7.46 (s, 1H), 6.36 – 6.32 (m, 2H),
5.34 (s, 1H), 3.30 (d, J = 5.0 Hz, 3H), 13C NMR (151 MHz,
DMSO-d6) δ 159.07, 156.99, 152.03, 151.88, 144.57, 142.09,
133.38, 125.10, 122.75, 116.70, 110.63, 109.04, 107.45, 104.07,
31.13, 28.69; HRMS (ESI, m/z): calcd for C17H12N2O6 (M+H+)
340.0695, found: 340.0697.
15. Jayabal, K.; Doraiswamy, M.; Paramasivan, T. P.; Synlett 2012,
23, 2894-2898.
16. Solid supported acid catalyst (a) Kalla, R. M. N.; Kim, M. R.;
Kim, Y. N.; Kim, I. New J. Chem. 2016, 40, 687-693; (b)
Tabrizian, E.; Amoozadeh, A. RSC Adv. 2016, 6, 96606-96615;
(c) Sharma, P.; Gupta, M. Green Chem. 2015, 17, 1100-1106; (d)
Kaur, M.; Sharma, S.; Bedi, P. M. S. Chinese Journal of Catalysis
2015, 36, 520-549; (e) Sharma, R. K.; Sharma, S.; Dutta, S.;
Zboril, R.; Gawande, M. B. Green Chem. 2015, 17, 3207-3230;
(f) Mennecke, K.; Kirschning, A. Beilstein. J. Org. Chem. 2009,
5, 21; (g) Cai, M.; Zheng, G.; Zha, L.; Peng, J. Eur. J. Org. Chem.
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48, 95-99.
4.2.26.
2-(methylamino)-3-nitro-4-(thiophen-2-yl)-4H,5H-
pyrano[3,2-c]chromen-5-one (4z). Yield 88%; yellow solid;
Mp: 266-268 C; IR (νmax) cm-1: 3184 (N-Hstr), 2988 & 2832 (C-
o
Hstr), 1708 ( C=Ostr), 1254 & 1130 (C-Ostr), 1629 & 1412
(C=Cstr), 1016 (C-O-Cstr); 1H NMR (600 MHz, DMSO-d6) δ
10.35 (s, 1H), 8.02 – 8.00 (m, 1H), 7.78 – 7.75 (m, 1H), 7.55 –
7.50 (m, 2H), 7.34 (t, J = 4.1 Hz, 1H), 6.97 (t, J = 3.2 Hz, 1H),
6.90 (dd, J = 8.4, 4.3 Hz, 1H), 5.48 (s, 1H), 3.30 (d, J = 4.3 Hz,
3H), 13C NMR (151 MHz, DMSO-d6) δ 159.26, 156.74, 152.37,
152.06, 144.28, 133.38, 126.73, 125.43, 125.12, 124.82, 122.87,
116.72, 112.57, 107.52, 106.21, 32.04, 28.71; HRMS (ESI, m/z):
calcd for C17H12N2O5 S (M+H+) 356.0467, found: 356.0467.
17. (a) Karami, B.; Ghashghaee, V.; Khodabakhshi, S.; Catal.
Commun. 2012, 20, 71-75; (b) Khodabakhshi, S.; Karami, B.;
Catal. Sci. Technol. 2012, 2, 1940-1944.
18. (a) Sagar Reddy, A. V.; Reddy, M. V.; Jeong, Y. T. Research on
Chemical Intermediates 2016, 42, 5209-5218; (b) Shinde, V. V.;
Jeong, Y. T. C. R. Chimie. 2015, 18, 449-455; (c) Atar, A. B.;
Jeong, Y. T. Tetrahedron Lett. 2013, 54, 5624-5628.
19. Reddy, M. V.; Dindulkar, S. D.; Jeong, Y. T. Tetrahedron Lett.
2011, 52, 4764-4767.
Supporting Information
20. Dindulkar, S. D.; Parthiban, P.; Jeong, Y. T. Monatsh Chem.
2012, 143, 113-118.
21. Shinde, V. V.; Reddy, M. V.; Kim, Y. H.; Cho, B. K.; Jeong, Y.
T. Monatsh Chem. 2015, 146, 673-682.
22. Shinde, V. V.; Min Lee, S.; Su Oh, J.; Lim, K. T.; Jeong, Y. T.
Synth. Commun. 2016, 46, 1145-1153.
23. Atar, A. B.; Kim, J. Su; Lim, K. T.; Jeong, Y. T. New J. Chem.
2015, 39, 396-402.
All Compounds NMR spectra were provided as
Supplementary material.
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