One-pot synthesis of 4H-chromene and dihydropyrano[3, 2-c]chromene derivatives in hydroalcoholic media

Article abstract of DOI:10.1590/s0103-50532011000500013

4ff-Chromenes and dihydropyrano[3, 2-c]chromenes are obtained in good to excellent yields by a simple, mild and efficient procedure using poly(N, N'-dibromo-N-ethyl-benzene-1, 3-disulfonamide) [PBBS] and N, N, N, N,-tetrabromobenzene-1, 3-disulfonamide [T

Full text of DOI:10.1590/s0103-50532011000500013

J. Braz. Chem. Soc., Vol. 22, No. 5, 905-909, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Article
A
One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-c]chromene Derivatives
in Hydroalcoholic Media
Ramin Ghorbani-Vaghei,* Zahra Toghraei-Semiromi and Rahman Karimi-Nami
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, 65174 Hamedan, Iran
4H-Cromenos e diidropirano[3,2-c]cromenos são obtidos em rendimentos bons a excelentes
através de um procedimento simples, brando e eficiente usando poli(N,N´-dibromo-N-etil-benzeno-
1,3-dissulfonamida) [PBBS] e N,N,N´,N´-tetrabromobenzeno-1,3-dissulfonamida [TBBDA] como
catalisadores.
4H-Chromenes and dihydropyrano[3,2-c]chromenes are obtained in good to excellent
yields by a simple, mild and efficient procedure using poly(N,N’-dibromo-N-ethyl-benzene-
1,3-disulfonamide) [PBBS] and N,N,N’,N’-tetrabromobenzene-1,3-disulfonamide [TBBDA ] as
catalysts.
Keywords: 4H-chromenes, dihydropyrano[3,2-c]chromenes, TBBDA, PBBS
Introduction
diseases, including Alzheimer,s disease, amyotrophic
lateral sclerosis, Parkinson,s disease, Huntington,s
disease, AIDS associated dementia and Down,s syndrome
as well as for the treatment of schizophrenia and
myoclonus.6 In addition, aminochromene derivatives
exhibit a wide spectrum of biological activities including
antihypertensive and anti-ischemic behavior.7-9 Also, a
number of 2-amino-4H-pyrans are useful as photoactive
materials.10
The development of multi-component reactions
(MCRs) has attracted much attention from the vantage
point of combinatorial and medicinal chemistry.1 Many
important heterocycle syntheses are multi-component
reactions. Recently, the synthesis of 4H-chromenes and
dihydropyrano[3,2-c]chromenes derivatives have attracted
great interest to their biological and pharmacological
activities. The 4H-chromene derivatives show various
pharmacological properties such as spasmolytic, diuretic,
anticoagulant, anticancer, and antianaphylactic activities.2
Substituted 4H-chromenes are particularly versatile
compounds that bind Bcl-2 protein (B-cell lymphoma 2)
and induce apoptosis in tumor cells. Specifically, Bcl-2
can contribute to neoplastic cell expansion by preventing
normal cell turnover caused by physiological cell death
mechanisms. High levels of the Bcl-2 gene expressions
are found in a wide variety of human cancers and can lead
to tumor cell resistance to conventional chemotherapy
and radiotherapy. Thus, Bcl-2 protein binding compounds
provide a promising lead for the development of potential
anticancer agents and direct methods for their synthesis are
highly desirable.3-5 Dihydropyrano[3,2-c]chromenes are
a class of important heterocycles that have been used as
cognitive enhancers, for the treatment of neurodegenerative
4H-Chromeneshavebeenpreparedfromsalicylaldehydes
and cyanoacetates in heterogeneous liquid phase catalysis
4,11
using Al2O3
and molecular sieves.5 They are also
synthesized in the presence of Zr(KPO4)212 and Amberlyst
A21®.13 Despite their importance from pharmacological,
industrial and synthetic point of views, comparatively few
methods for accessing pyrano[3,2-c]chromene derivatives
have been reported.14-16 2-Amino-4-aryl-5-oxo-4H,
5H-pyrano-[3,2-c]chromene-3-carbonitriles have already
been prepared in the presence of organic bases like piperidine
or pyridine in an organic solvent, i.e., ethanol and pyridine.14
They are also obtained in the presence of diammonium
16
hydrogen phosphate,15 H6P2W18O62 18H2O, DBU17 and
•
K2CO3 under microwave irradiation.18
However, some of these protocols require long reaction
times, multi-step reactions, complex synthetic pathways
and afford products with only modest yields. Therefore,
the introduction of milder, faster and more ecofriendly
methods, accompanied with higher yields is needed.
*e-mail: rgvaghei@yahoo.com

906
One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-c]chromene Derivatives
J. Braz. Chem. Soc.
Results and Discussion
1,3-disulfonamide) [PBBS]19-22 in organic synthesis, we
report here a convenient method for the preparation of
4H-chromenes from salicylaldehydes and malononitrile or
ethyl cyanoacetate in aqueous ethanol (H2O:EtOH, (1:1))
at room temperature (Scheme 1 and Table 1).
In continuation of our interest in the application
of N,N,N’,N’-tetrabromo benzene-1,3-disulfonamide
[TBBDA] and poly(N,N’-dibromo-N-ethyl-benzene-
Also the synthesis of dihydropyrano[3,2-c]chromenes
was achieved by the three-component condensation of an
aromatic aldehyde, malononitrile and 4-hydroxycoumarin in
the presence of the catalysts. The reaction was carried out in
aqueousethanolatrefluxusingTBBDAandPBBSascatalysts
togiveproductsingoodtohighyields(Scheme2andTable2).
NC
R
CHO
R
CN
R
TBBDA or PBBS
+
H2O:EtOH (1:1), r.t.
OH
O
NH2
R = CO2Et or CN
Scheme 1.
Table 1. Synthesis of various 4H-chromenes using TBBDA and PBBS at room temperature
TBBDA
time/min
PBBS
time/min
Entry
1
Aldehyde
R
Producta
Ref.
13
Yield/(%)
92(55)b
Yield/(%)
NC
CN
CN
CHO
OH
CN
45(180)b
70
90
O
NH2
CN
NC
CHO
CN
2
CN
120
92
150
92
13
OH
O
NH2
OMe
OMe
NC
CN
MeO
CHO
MeO
O2N
Br
CN
3
4
5
CN
CN
CN
135
30(180)b
300
72
85(55)b
83
180
65
99
96
97
-
OH
O
NH2
CN
NC
NC
NC
CHO
OH
O2N
CN
13
13
O
NH2
CN
Br
CHO
OH
CN
270
O
NH2
CN
Br
CHO
OH
Br
CN
6
CN
90
98
15
94
13
O
NH2
Br
Br
NC
CN
Cl
CHO
OH
Cl
CN
7
8
CN
CN
240
420
95
76
210
60
88
82
-
O
NH2
NC
CN
CN
CHO
OH
13
O
NH2
NC
CO2Et
CHO
OH
CO2Et
9
CO2Et
CO2Et
180
270
82
92
210
260
85
88
12
12
O
NH2
OMe
OMe
NC
CO2Et
Cl
CHO
OH
Cl
CO2Et
10
O
NH2
aProducts were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic methods. bWithout using the
catalysts.

Vol. 22, No. 5, 2011
Ghorbani-Vaghei et al.
907
NH2
CN
Ar
OH
O
O
O
CN
CN
TBBDA or PBBS
+
+
H
Ar
H2O:EtOH (1:1),
O
O
O
reflux
Scheme 2.
Table 2. Synthesis of various dihydropyrano[3,2-c]chromenes using TBBDA and PBBS under refluxing H2O:EtOH (1:1)
TBBDA
time/min
PBBS
Entry
1
ArCHO
PhCHO
Producta
Ref.
15
Yield/(%)
time/min
120
Yield/(%)
NH2
O
CN
150
195
75
88
75
O
O
NH2
CN
O
O
2
4-Cl-C6H4CHO
4-OMe-C6H4CHO
4-Me-C6H4CHO
4-NO2-C6H4CHO
3-NO2-C6H4CHO
4-Br-C6H4CHO
89
81
180
150
200
150
240
90
90
73
79
90
83
82
80
82
94
15
15
17
15
15
15
15
15
5
O
Cl
OMe
Me
NH2
CN
O
3
O
O
NH2
CN
O
4
50
72
O
O
NH2
CN
O
5
170(240)b
180
120
75
91(40)b
O
O
NO2
NH2
CN
O
6
97
NO2
O
O
NH2
CN
O
7
92
O
O
Br
NH2
CN
Cl
O
8
2,4-Cl2-C6H4CHO
2,3-Cl2-C6H4CHO
2,6-Cl2-C6H4CHO
76
25
O
O
Cl
NH2
CN
Cl
O
9
60
88
20
Cl
O
O
NH2
CN
Cl
O
O
10
90
90
30
Cl
O
NH2
CN
O
O
OMe
OMe
11
3,4,5-(OMe)3-C6H4CHO
300
89
330
92
-
O
OMe
aProducts were characterized from their physical properties, by comparison with authentic samples, and by spectroscopic methods. bWithout using the catalysts.

908
One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-c]chromene Derivatives
J. Braz. Chem. Soc.
The advantages of PBBS and TBBDA are: (i) ease
Supplementary Information
of preparation; (ii) reagent stability under atmospheric
conditions for two months; (iii) possibility of re-use.
In conclusion, we have developed an efficient
procedure for the synthesis of 4H-chromenes and
dihydropyrano[3,2-c]chromenes derivatives in aqueous
media using [TBBDA] and [PBBS]. This method offers
several advantages such as inexpensive catalysts, easy
synthetic procedure, high yields, simple work-up procedure
and easy product isolation.
1
Supplementary characterization data and H NMR
spectra are available, free of charge at http://jbcs.sbq.org.br
as a PDF file.
Acknowledgments
We are thankful to Bu-Ali Sina University, Center
of Excellence in Development of Chemical Methods
(CEDCM) for financial support.
Experimental
References
All commercially available chemicals were obtained
from Merck and Fluka, and used without further
purifications unless otherwise stated. H NMR and
13C NMR spectra were recorded on a Jeol 90 MHz and
a Bruker 300 MHz FT NMR spectrometers using TMS
as internal standard and chemical shifts in d (ppm).
Infrared (IR) spectra were acquired on a Perkin Elmer GX
FT-IR spectrometer. All yields refer to isolated products.
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Tetrahedron Lett. 2000, 41, 6993.
General procedure for the preparation of 4H-chromenes
A mixture of salicylaldehyde (5 mmol), malononitrile
(1.2 mmol) and TBBDA (0.18 mmol) or PBBS (0.1 g)
in H2O (5 mL) and EtOH (5 mL) was stirred at room
temperature for the appropriate time. After completion
of the reaction, which was monitored by TLC, the solid
product was collected by filtration, washed with water
and aqueous ethanol and purified by recrystallization from
ethanol.
4. Fujimoto, A.; Sakurai, A.; Synthesis 1977, 871.
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W.; PCT IntAppl WO 0075123 2000; Chem. Abstr. 2001, 134,
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7555.
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Showell, G. A.; J. Med. Chem. 1984, 27, 1127.
9. Evans, J. M.; Fake, C. S.; Hamilton, T. C.; Poyser, R. H.; Watts,
E. A.; J. Med. Chem. 1983, 26, 1582.
General procedure for the preparation of 2-amino-5-oxo-
dihydropyrano[3,2-c]chromenes
A mixture of aldehyde (10 mmol), malononitrile
(1.2 mmol), 4-hydroxycoumarin (10 mmol) and TBBDA
(0.18 mmol) or PBBS (0.1 g) in H2O (5 mL) and EtOH
(5 mL) was stirred under reflux for the appropriate time.
After completion of the reaction, which was monitored
by TLC, the mixture was monitored by TLC, the mixture
was cooled to room temperature. The solid product was
collected by filtration, washed with water and aqueous
ethanol and purified by recrystallization from ethanol.
10. Arnesto, D.; Horspool, W. M.; Martin, N.; Romos, A.; Seoane,
C.; J. Org. Chem. 1989, 54, 3069.
11. Shi, D. Q.;Wang, X. S.; Tu, S. J.;Yao, C. S.;Wang,Y. C.; Jiegou
Huaxue 2002, 21, 60.
12. Curini, M.; Epifano, F.; Chimichi, S.; Montanari, F.; Nochetti,
M.; Rosati, O.; Tetrahedron Lett. 2005, 46, 3497.
13. Yadav, J. S.; Reddy, B. V. S.; Gupta, M. K.; Prathap, I.; Pandey,
S. K.; Catal. Commun. 2007, 8, 2208.
14. Skaker, R. M.; Pharmazie 1996, 51, 148.
15. Abdolmohammadi, S.; Balalaie, S.; Tetrahedron Lett. 2007, 48,
3299.
Recycling of the catalysts
16. Heravi, M. M.; Jani, B. A.; Derikvand, F.; Bamoharram, F. F.;
Oskooie, H. A.; Catal. Commun. 2008, 10, 272.
17. Khurana, J. M.; Nand, B.; Saluja, P.; Tetrahedron 2010, 66,
5637.
The catalysts were recovered by evaporation of the
solvent and washing of the solid with dichloromethane.

Vol. 22, No. 5, 2011
Ghorbani-Vaghei et al.
909
18. Kidwai, M.; Saxena, S.; Synth. Commun. 2006, 63, 2737.
19. Ghorbani-Vaghei, R.; Jalili, H.; Synthesis 2005, 1099.
20. Ghorbani-Vaghei, R.; Akbari-Dadamahaleh, S.; Tetrahedron
Lett. 2009, 50, 1055.
22. Ghorbani-Vaghei, R.; Zolfigol, M.,A.; Chegeny, M.; Veisi, H.;
Tetrahedron Lett. 2006, 47, 4505.
Submitted: September 20, 2010
21. Ghorbani-Vaghei, R.; Khazaei, A.; Tetrahedron Lett. 2003, 44,
7525.
Published online: February 3, 2011

J. Braz. Chem. Soc., Vol. 22, No. 5, S1-S9, 2011.
Printed in Brazil - ©2011 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Supplementary Information
SI
One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-c]chromene Derivatives
in Hydroalcoholic Media
Ramin Ghorbani-Vaghei,* Zahra Toghraei-Semiromi and Rahman Karimi-Nami
Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University, 65174 Hamedan, Iran
Analytical data for selected compounds
2-Amino-6-bromo-3-cyano-4-(1,1-dicyanomethyl)-4H-
chromene (Table 1, entry 5)
2-Amino-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene
(Table 1, entry 1)
mp 163-164 ºC; IR (KBr) νmax/cm-1: 3471, 3349,
2885, 2189, 1635, 1597, 1596, 1426, 1228, 817, 1H NMR
(DMSO, 90 MHz), d 4.76 (d, 2H, J 3.5 Hz, CH), 5.19 (d,
2H, J 3.5 Hz, CH), 7.72-7.96 (m, 5H, aromatic and NH2).
mp 147-148 ºC; IR (KBr) νmax/cm-1: 3486, 3386,
3181, 2201, 1643, 1600, 1568, 1408, 1236, 754, 1H NMR
(DMSO, 90 MHz), d 4.82 (d, 1H, J 3.5 Hz, CH), 4.95
(d, 1H, J 3.60 Hz, CH), 6.69 (s, 2H, NH2), 7.38 (m, 4H,
aromatic).
2-Amino-6, 8-dibromo-3-cyano-4-(1,1-dicyanomethyl)-4H-
chromene (Table 1, entry 6)
mp 182-183 ºC; IR (KBr) νmax/cm-1: 3414, 3332,
2885, 2197, 1655, 1600, 1562, 1457, 1433, 871, 1H NMR
(DMSO, 90 MHz), d 4.76 (d, 2H, J 3.6 Hz, CH), 5.17 (d,
2H, J 3.6 Hz, CH), 7.74-7.96 (m, 4H, aromatic and NH2).
2-Amino-8-methoxy-3-cyano-4-(1,1-dicyanomethyl)-4H-
chromene (Table 1, entry 2)
mp 188-189 ºC; IR (KBr) νmax/cm-1: 3464, 3356, 2910,
2192, 1642, 1613, 1552, 1488, 1420, 1218, 750, 1H NMR
(DMSO, 90 MHz), d 3.83 (s, 3H, CH3), 4.53 (d, 1H, J
3.8 Hz, CH), 5.01 (d, 1H, J 3.90 Hz, CH), 7.07 (m, 3H,
aromatic), 7.52 (s, 2H, NH2).
2-Amino-6-chloro-3-cyano-4-(1,1-dicyanomethyl)-4H-
chromene (Table 1, entry 7)
mp 151-154 ºC; IR (KBr) νmax/cm-1: 3445, 3337,
2862, 2194, 1644, 1600, 1572, 1457, 1483, 819, 1H NMR
(DMSO, 90 MHz), d 4.62 (d, 1H, J 3.8 Hz, CH), 5.14 (d,
1H, J 3.8 Hz, CH), 7.10-7.57 (m, 5H, aromatic and NH2),
13C NMR [DMSO-d6, 300 MHz]: d 163.7, 149.0, 130.5,
129.0, 128.9, 120.3, 119.6, 119.2, 118.8, 113.4, 113.2,
48.9, 37.3. Anal. Calc. C, 57.69; H, 2.61; N, 20.07%.
Found: C, 57.53; H, 2.36; N, 19.94%. m/z 270.
2-Amino-6-methoxy-3-cyano-4-(1,1-dicyanomethyl)-4H-
chromene (Table 1, entry 3)
mp 184-185 ºC; IR (KBr) νmax/cm-1: 3402, 3342,
3218, 2185, 1659, 1587, 1426, 1217, 1037, 820, 1H NMR
(DMSO, 90 MHz), d 3.73 (s, 3H, CH3), 4.54 (s, 1H, CH),
5.09 (s, 1H, CH), 7.02 (s, 3H, aromatic), 7.41 (s, 2H, NH2).
13C NMR [DMSO-d6, 300 MHz]: d 164.1, 156.3, 144.0,
120.0, 119.1, 118.4, 117.7, 116.3, 113.6, 113.4, 113.4,
56.0, 48.79, 38.0.Anal. Calc. C, 63.15; H, 3.79; N, 21.04%.
Found: C, 62.90; H, 3.51; N, 20.65%. m/z 266.
2-Amino-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c]
chromene-3-carbonitrile (Table 2, entry 1)
mp 260-264 ºC; IR (KBr) νmax/cm-1: 3379, 3305, 2196,
1713, 1676, 1637, 1H NMR (DMSO, 90 MHz), d 4.45 (s,
1H, CH), 7.28-7.86 (m, 11H, aromatic and NH2).
2-Amino-6-nitro-3-cyano-4-(1,1-dicyanomethyl)-4H-
chromene (Table 1, entry 4)
mp 180-181 ºC; IR (KBr) νmax/cm-1: 3408, 3319,
3074, 2199, 1659, 1608, 1526, 1352, 1262, 748, 1H NMR
(DMSO, 90 MHz), d 4.76 (d, 2H, J 3.7 Hz, CH), 5.18 (d,
2H, J 3.7 Hz, CH), 7.32-7.42 (m, 1H, aromatic), 7.77 (s,
2H, NH2), 8.23-8.50 (m, 2H, aromatic).
2-Amino-4-(4-chlorophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 2)
mp 265-267 ºC; IR (KBr) νmax/cm-1: 3380, 3291, 3189,
2191, 1713, 1676, 1H NMR (DMSO, 90 MHz), d 4.72 (s,
1H, CH), 7.40-8.13 (m, 10H, aromatic and NH2).
*e-mail: rgvaghei@yahoo.com

S2
One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-C]chromene Derivatives
J. Braz. Chem. Soc.
2-Amino-4-(4-methoxyphenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 3)
mp 246-249 ºC; IR (KBr) νmax/cm-1: 3500, 3450, 3350,
2208, 1647,1174, 1H NMR (DMSO, 90 MHz), d 3.71 (s,
3H, CH3), 4.39 (s, 1H, CH), 6.81-7.85 (m, 10H, aromatic
and NH2).
2-Amino-4-(2,4-dichlorophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 8)
mp 255-258 ºC; IR (KBr) νmax/cm-1: 3459, 3290, 3163,
2199, 1716, 1673, 1630, 1589,1061, 761. 1H NMR (DMSO,
90 MHz), d 4.94 (s, 1H, CH), 7.34-7.92 (m, 9H, aromatic
and NH2).
2-Amino-5-oxo-4-p-tolyl-4,5-dihydropyrano[3,2-c]
chromene-3-carbonitrile (Table 2, entry 4)
2-Amino-4-(2,3-dichlorophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 9)
mp 273-276 ºC; IR (KBr) νmax/cm-1: 3405, 3305, 3181,
2199, 1711, 1674, 1602, 1492,1062, 764. 1H NMR (DMSO,
90 MHz), d 5.07 (s, 1H, CH), 7.33-7.96 (m, 9H, aromatic
and NH2).
mp 252-254 ºC; IR (KBr) νmax/cm-1: 3388, 3311, 3189,
1
2194, 1713, 1676, 1637, H NMR (DMSO, 90 MHz),
d 2.25 (s, 3H, CH3), 4.40 (s, 1H, CH), 7.12-7.93 (m, 10H,
aromatic and NH2).
2-Amino-4-(4-nitrophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 5)
mp 255-258 ºC; IR (KBr) νmax/cm-1: 3482, 3370, 3071,
2196, 1718, 1673, 1606, 1505,1373, 1348, 766. 1H NMR
(DMSO, 90 MHz), d 4.66 (s, 1H, CH), 7.47-8.21 (m, 10H,
aromatic and NH2).
2-Amino-4-(2,6-dichlorophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 10)
mp 274-277 ºC; IR (KBr) νmax/cm-1: 3419, 3277, 3173,
2200, 1707, 1673, 1633, 1599,1379, 758. 1H NMR (DMSO,
90 MHz), d 5.51 (s, 1H, CH), 7.35-7.92 (m, 9H, aromatic
and NH2).
2-Amino-4-(3-nitrophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 6)
mp 256-259 ºC; IR (KBr) νmax/cm-1: 3408, 3324, 3192,
2194, 1710, 1677, 1608, 1528,1380, 1347, 764. 1H NMR
(DMSO, 90 MHz), d 4.72 (s, 1H, CH), 7.54-8.12 (m, 10H,
aromatic and NH2).
2-Amino-5-oxo-4-(3,4,5-trimethoxyphenyl)-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 11)
mp 224-226 ºC; IR (KBr) νmax/cm-1: 3425, 3321, 2191,
1672, 1595, 1375, 1154, 1H NMR (DMSO, 90 MHz), d 3.63
(s, 3H, CH3), 3.71 (s, 6H, CH3), 4.43(s, 1H, H), 6.52 (s, 2H,
NH2), 7.36-7.93 (m, 6H, aromatic), 13C NMR [DMSO-d6,
300 MHz]: d 160.1, 158.5, 154.0, 153.3, 152.6, 139.4,
137.1, 133.3, 125.1, 123.0, 119.7, 117.0, 113.6, 105.4,
104.1, 60.4, 58., 56., 37.7. Anal. Calc. C, 65.02; H, 4.46;
N, 6.89%. Found: C, 65.0; H, 4.27; N, 6.93%. m/z 404.
2-Amino-4-(4-bromophenyl)-5-oxo-4,5-dihydro-
pyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 7)
mp 255-257 ºC; IR (KBr) νmax/cm-1: 3387, 3309, 3188,
2181, 1710, 1677, 1602, 1577,1062, 758. 1H NMR (DMSO,
90 MHz), d 4.46 (s, 1H, CH), 7.19-7.84 (m, 10H, aromatic
and NH2).
Figure S1. 1H NMR (DMSO) 2-amino-8-methoxy-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 2).

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Figure S2. 1H NMR (DMSO) 2-amino-6-methoxy-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 3).
Figure S3. 13C NMR (DMSO) 2-amino-6-methoxy-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 3).
Figure S4. 1H NMR (DMSO) 2-amino-6-nitro-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 4).

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One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-C]chromene Derivatives
J. Braz. Chem. Soc.
Figure S5. 1H NMR (DMSO) 2-amino-6-bromo-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 5).
Figure S6. 1H NMR (DMSO) 2-amino-6-chloro-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 7).
Figure S7. 13C NMR (DMSO) 2-amino-6-chloro-3-cyano-4-(1,1-dicyanomethyl)-4H-chromene (Table 1, entry 7).

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Figure S8. 1H NMR (DMSO) 2-amino-5-oxo-4-phenyl-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 1).
Figure S9. 1H NMR (DMSO) 2-amino-4-(4-chlorophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 2).
Figure S10. 1H NMR (DMSO) 2-amino-4-(4-methoxyphenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 3).

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One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-C]chromene Derivatives
J. Braz. Chem. Soc.
Figure S11. 1H NMR (DMSO) 2-amino-5-oxo-4-p-tolyl-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 4).
Figure S12. 13C NMR (DMSO) 2-amino-5-oxo-4-p-tolyl-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 4).
Figure S13. 1H NMR (DMSO) 2-amino-4-(4-nitrophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 5).

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Figure S14. 1H NMR (DMSO) 2-amino-4-(3-nitrophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 6).
Figure S15. 1H NMR (DMSO) 2-amino-4-(4-bromophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 7).
Figure S16. 1H NMR (DMSO) 2-amino-4-(2,4-dichlorophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 8).

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One-Pot Synthesis of 4H-Chromene and Dihydropyrano[3,2-C]chromene Derivatives
J. Braz. Chem. Soc.
Figure S17. 1H NMR (DMSO) 2-amino-4-(2,3-dichlorophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 9).
Figure S18. 1H NMR (DMSO) 2-amino-4-(2,6-dichlorophenyl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 10).
Figure S19. 1H NMR (DMSO) 2-amino-5-oxo-4-(3,4,5-trimethoxyphenyl)-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 11).

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Figure S20. 13C NMR (DMSO) 2-amino-5-oxo-4-(3,4,5-trimethoxyphenyl)-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (Table 2, entry 11).