Aqua one-pot, three-component synthesis of dihydropyrano[3,2-c]chromenes and amino-benzochromenes catalyzed by sodium malonate

Article abstract of DOI:10.1007/s11164-017-3011-7

The widespread biological properties of dihydropyrano[3,2-c]chromenes, 2-amino-4-aryl-4H-benzo[h]chromenes, and 3-amino-1-aryl-1H-benzo[f]chromenes have led to increasing efforts for the development of tremendously effective synthetic protocols aimed at their synthesis. In this contribution, sodium malonate was employed for the first time as an efficient catalyst for the one-pot, three-component tandem Knoevenagel–cyclocondensation reaction of 4-hydroxycoumarin (or naphthols), malononitrile/ethyl cyanoacetate, and various aldehydes. These compounds underwent Knoevenagel–Michael–Thorpe–Ziegler cyclization upon heating at 70?°C in water to give the respective medicinally relevant dihydropyrano[3,2-c]chromenes and amino-benzochromenes. The method is versatile and amenable to many substrates as it requires no specialized devices such as microwave, ultrasound and ball-milling. Also, the salient features of this high-yielding protocol are green reaction conditions, the use of commercially available catalyst, easy purification processes by a simple filtration, and relatively shorter reaction times.

Full text of DOI:10.1007/s11164-017-3011-7

Res Chem Intermed
DOI 10.1007/s11164-017-3011-7
Aqua one-pot, three-component synthesis
of dihydropyrano[3,2-c]chromenes and amino-
benzochromenes catalyzed by sodium malonate
Hamzeh Kiyani1
Mohsen Tazari1
•
Received: 25 April 2017 / Accepted: 16 June 2017
Ó Springer Science+Business Media B.V. 2017
Abstract The widespread biological properties of dihydropyrano[3,2-c]chromenes,
2-amino-4-aryl-4H-benzo[h]chromenes, and 3-amino-1-aryl-1H-benzo[f]chromenes
have led to increasing efforts for the development of tremendously effective syn-
thetic protocols aimed at their synthesis. In this contribution, sodium malonate was
employed for the first time as an efficient catalyst for the one-pot, three-component
tandem Knoevenagel–cyclocondensation reaction of 4-hydroxycoumarin (or naph-
thols), malononitrile/ethyl cyanoacetate, and various aldehydes. These compounds
underwent Knoevenagel–Michael–Thorpe–Ziegler cyclization upon heating at
70 °C in water to give the respective medicinally relevant dihydropyrano[3,2-
c]chromenes and amino-benzochromenes. The method is versatile and amenable to
many substrates as it requires no specialized devices such as microwave, ultrasound
and ball-milling. Also, the salient features of this high-yielding protocol are green
reaction conditions, the use of commercially available catalyst, easy purification
processes by a simple filtration, and relatively shorter reaction times.
Keywords Sodium malonate Á Dihydropyrano[3,2-c]chromene Á Green
chemistry Á Three-component reaction Á Amino-benzochromene Á Water
Introduction
The chromene skeleton is considered as one of the most important heterocyclic ring
systems in organic synthetically chemistry and is implanted in many biologically
active compounds. In recent years, densely functionalized chromenes and their
derivatives have received considerable attention because of various applications in
&
Hamzeh Kiyani
hkiyani@du.ac.ir
1
School of Chemistry, Damghan University, Damghan 36719-41167, Iran
123

H. Kiyani, M. Tazari
medicinal chemistry. Among functionalized chromenes known so far, dihydropy-
rano[3,2-c]chromenes and amino-benzochromenes as ‘privileged medicinal scaf-
folds’ possess a wide range of fascinating biological activities, such as
antituberculosis [1], anti-oxidant [2], acetylcholinesterase (AChE) inhibitoy [3],
antibacterial [4, 5], anti-anaphylactic [6], antimicrobial [7–9], antifungal [10], anti-
inflammatory [11], anti-rheumatic [12], antitumor [13–16], and antiproliferative
[17, 18]. Structures of some derivatives of these bioactive scaffolds can be seen in
Fig. 1.
Up to now, keeping in view the importance of dihydropyrano[3,2-c]chromene
frameworks and amino-benzochromene heterocyclic compounds, various synthetic
methods have been reported for the synthesis of these heterocycles. A large number
of homogeneous and heterogeneous catalysts have been used for this purpose,
including starch [19], urea [20], thiourea dioxide (TUD) [21], hexamethylenete-
tramine (HMTA) [22], 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) [23], meglumine
[24], N-propylpiperazine sodium n-propionate (SBPPSP) [25], poly(4-vinylpyr-
idine) [26], Amberlyst A21 [27], borax [28], BF3ÁSiO2 [29], CuO nanoparticles [30],
4-(dimethylamino)pyridine (DMAP) [31], silica gel [32], morpholine [33], ammo-
nium or sodium formate [34], cetyltrimethylammonium bromide in water [35],
I2/K2CO3 [36], cetyltrimethylammonium bromide (CTABr) using ultrasound irra-
diation [37], NaHCO3 [38], basic alumina [39], nano-sized MgO [40], nano-
structured diphosphate Na2CaP2O7 [41], triazinefunctionalised ordered mesoporous
organosilica [42], potassium phosphate tribasic trihydrate [43], piperidine under
microwave heating [44], Mg/Al hydrotalcite [45], Preyssler heteropolyacid
[46], 1,4-diazabicyclo[2.2.2]octane (DABCO) entrapped in agar–agar [47], CeO2/
CaO nanocomposite oxide [48], nano-polypropylenimine dendrimer (DAB-PPI-G1)
Lewis base [49], VCaHAa [50], poly(4-vinylpyridine) [51], diammonium hydrogen
phosphate [52], amino-functionalized MCM-41 [53], piperidine [14–16], imidazole
[54], ionic liquids [55], nano-copper chromite (nano-CuCr2O4) [56], tetragonal
Fig. 1 Structures of some synthetically bioactive dihydropyrano[3,2-c]chromenes and amino-
benzochromenes
123

Aqua one-pot, three-component synthesis of…
ZrO2 nanoparticle (t-ZrO2 NP) [57], tetrabutylammonium chloride (TBAC) [58], (4-
dimethylaminopyridine) functionalized polyacrylonitrile fiber catalyst (PANDMAPF)
[59], piperazine-functionalized Fe3O4/SiO2 magnetite nanoparticle [60], and Triton
B [61]. Special apparatus such as ultrasound [62–64], microwave [65–67], and ball
milling [68] have also been utilized for the synthesis of such biologically significant
compounds. We have recently used potassium phthalimide (PPI) [69–71], potassium
hydrogen phthalate (KHP) [72], and N,N-dimethylbenzylamine (DMBA) [73, 74] as
catalysts for the synthesis of diversely 4H-pyran-annulated molecules.
In view of the aforementioned applications of densely functionalized chromenes,
using an efficient catalyst toward the construction of dihydropyrano[3,2-c]chromene
and amino-benzochromene scaffolds via simple multicomponent reaction (MCR)
remains an issue of interest.
A MCR was recognized as an efficacious method for the construction of valuable
organic compounds and pharmacologically active molecules from at least three
reactants in a single vessel. Atomic and structural economy, mild reaction
conditions, step economy, high convergence, high bond-forming index, substantial
capacity to create molecular complexity and diversity, the product diversity, and the
avoidance of complicated separation and purification processes are the chemical
benefits of MCRs [75–81]. The development of environmentally friendly organic
transformations without using any organic solvent is still a challenge. From an
economical and green chemistry point of view, aqua-mediated chemical reactions
have been considered as useful protocols in organic synthesis due to water being an
easily available, clean, safe, non-toxic, noncombustible, non-explosive, the most
environmentally benign, low-cost, and recyclable medium. Considering the above-
mentioned benefits of water as the reaction medium, in recent years many chemists
have been interested to use water in various organic transformations [82–88]. In the
present study, the synthesis of functionalized chromenes from 4-hydroxycoumarin
(or 1-naphthol and 2-naphthol), malononitrile/ethyl cyanoacetate, and diversified
aldehydes in the presence of sodium malonate (SM) at 70 °C in water as an
environmentally friendly solvent is reported.
Materials and methods
Instruments and characterization
Melting points were measured on a Bu¨chi 510 melting point apparatus and are
uncorrected. 1H NMR and 13C NMR spectra were recorded at ambient temperature
on a Bruker Avance DRX-500 MHz spectrophotometer using DMSO-d6 as the
solvent. Elemental microanalyses were performed on an Elementar Vario EL III
analyzer. The purity of the synthesized compounds as well as the progress of the
reactions were monitored by thin layer chromatography (TLC) analysis on Merck
pre-coated silica gel 60F254 aluminum sheets, visualized by UV light. All the
targeted products are reported in the literature and are characterized by
comparison of their spectral and physical data on the basis of literature
descriptions.
123

H. Kiyani, M. Tazari
General procedure for the synthesis of dihydropyrano[3,2-c]chromenes (4a–
u), 2-amino-4-aryl-4H-benzo[h]chromenes (6a–h), and 3-amino-1-aryl-1H-
benzo[f]chromenes (7a–i)
A mixture of 4-hydroxycoumarin/1-naphthol/2-naphthol (1, 6, 7, 1 mmol), aldehyde
(2, 1 mmol), malononitrile/ethyl cyanoacetate (3, 1 mmol), water (5 mL) and SM
(10 mol%) was heated with stirring at 70 °C for the required times. After
completion of the reaction (monitored by TLC analysis), the reaction mixture was
gradually cooled to room temperature and the resulting precipitates were collected
by filtration, washed with cold water and air-dried to give the pure corresponding
products. The solvent was removed from the filtrate to recover the catalyst and
reused for subsequent runs. The identity of the known products was confirmed by
comparison of their spectroscopic data and physical properties with those described
in the respective literature.
Data for 2-Amino-4-(3-nitrophenyl)-5-oxo-4H,5H-pyrano-[3,2-c]chromene-3-
carbonitrile (4c)
M.p. 259–261 °C (255–257 °C, Lit. [19]); IR (KBr): 3435, 3376, 3274, 2210, 1705,
1
1670, 1614, 1525, 1460, 1375, 1220, 1117, 1058, 783 cm-1; H NMR (500 MHz,
DMSO-d6): d 4.74 (s, 1H), 7.46–7.74 (m, 6H), 7.82 (d, J = 7.8 Hz, 1H), 7.93 (dd,
J = 1.4, 7.9 Hz, 1H), 8.12–8.15 (m, 2H); 13C NMR (125 MHz, DMSO-d6): d 37.5,
57.8, 103.7, 113.8, 117.5, 119.8, 123.1, 123.3, 123.5, 125.6, 130.9, 135.6, 146.4,
148.7, 153.1, 154.7, 158.9, 159.0, 160.5. Anal. Calcd. for C19H11N3O5 (%): C,
63.15; H, 3.07; N,11.63. Found: C, 63.12; H, 3.05; N, 11.59.
Data for 2-amino-4-(4-chlorophenyl)-4H-benzo[h]chromene-3-carbonitrile (6d)
M.p. 231–233 °C (232–234 °C, Lit. [44]); IR (KBr): 3454, 3335, 2204, 1669, 1602,
1572, 1415, 1380,1105 cm-1; 1H NMR (500 MHz, DMSO-d6), d: 4.56 (s, 1H), 6.68
(s, 2H), 7.02 (d, J = 8.7 Hz, 1H), 7.19–7.34 (m, 4H), 7.43–7.48 (m, 3H), 7.79 (d,
J = 7.1 Hz, 1H), 8.15 (d, J = 8.2 Hz, 1H); 13C NMR (125 MHz, DMSO-d6): d
42.4, 55.6, 119.9, 120.6, 122.2, 122.4, 123.7, 125.4, 125.9, 126.6, 127.5, 128.7,
130.2, 132.6, 133.8, 142.4, 146.8, 160.8. Anal. Calcd. for C20H13ClN2O (%): C,
72.18; H, 3.94; N, 8.42. Found: C, 72.17; H, 3.92; N, 8.46.
Scheme 1 Sodium malonate catalyzed one-pot, three-component reaction of 4-hydroxycoumarin (1),
cyano compounds (3a and 3b) and aldehydes (2) at 70 °C in H2O
123

Aqua one-pot, three-component synthesis of…
Scheme 2 Sodium malonate catalyzed one-pot, three-component synthesis of 2-amino-4-aryl-4H-
benzo[h]chromenes (6a–h) and 3-amino-1-aryl-1H-benzo[f]chromenes (7a–l) at 70 °C in H2O
Table 1 Optimization of the reaction conditions for the synthesis of 2-amino-4-(3-nitrophenyl)-5-oxo-
4H,5H-pyrano[3,2-c]chromene-3-carbonitrile (4c)
Entry
Catalyst (mol%)
Solvent
Temp. (°C)
Time (min)
Isolated yields (%)
1
–
H2O
rt
120
60
60
60
60
60
45
30
15
20
20
20
20
20
20
20
Trace
25
2
–
H2O
Reflux
rt
3
5
H2O
30
4
10
15
20
10
10
10
10
10
10
10
10
10
10
H2O
rt
34
5
H2O
rt
34
6
H2O
rt
38
7
H2O
45
60
70
70
70
70
70
70
70
70
65
8
H2O
87
9
H2O
96
10
11
12
13
14
15
16
EtOH
MeCN
1,4-dioxane
CH2Cl2
EtOAc
CHCl3
H2O/EtOH
53
Trace
Trace
Trace
Trace
Trace
67
Reaction conditions: a well ground mixture of 4-hydroxycoumarin (1, 1 mmol), 3-nitrobenzaldehyde (2c,
1 mmol), malononitrile (3a, 1 mmol), solvent (5 mL), catalyst and magnetic stirring at different tem-
peratures rt room temperature
Optimized conditions shown in bold
Results and discussion
This work is the first report on the use of sodium malonate (SM) for the synthesis of
dihydropyrano[3,2-c]chromenes (4a–u) (Scheme 1), 2-amino-4-aryl-4H-benzo[h]chro-
mene and 3-amino-1-aryl-1H-benzo[f]chromene scaffolds (6a–h and 7a–l) (Scheme 2).
123

H. Kiyani, M. Tazari
Initially, 4-hydroxycoumarin (1), 3-nitrobenzaldehyde (2c) and malononitrile
(3a) were chosen as the model substrates to optimize the reaction conditions
including the effect of catalyst loading, the role of the solvents and reaction
temperatures (Table 1). The result showed that 10 mol% sodium malonate (SM)
was the most effective catalyst loading giving the product higher yields (96%) and
lower reaction times (15 min). Among several solvents screened, water was found
to be the best solvent. It was also found that the most suitable temperature is 70 °C.
Consequently, the optimized reaction conditions were 10 mol% SM in water at
70 °C within 15 min (Table 1, entry 9).
After finding the proper reaction parameters, we studied the scope of this three-
component reaction (3CR) by varying the structure of the aldehydes and active
cynano-containing compounds. The reactions proceeded cleanly under green
optimized reaction conditions.
Interestingly, almost all the substrates gave the desired dihydropyrano[3,2-
c]chromene heterocycles (4a–u) in good to excellent yields of 88–96% within the
Table 2 Synthesis of the dihydropyrano[3,2-c]chromene derivatives (4a–u) catalyzed by sodium
malonate
Entry Aldehyde
Cyano
compound/
Z
Product Time Yield
(min) (mol%)a
Mp (°C)
Found
Reported
references
1
C6H5CHO
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
4a
4b
4d
4e
4f
20
25
12
15
15
20
25
30
22
25
25
20
37
25
25
30
30
35
25
40
94
91
97
94
95
92
93
94
95
94
91
96
90
90
89
89
91
90
90
88
260–261 258–260 [19]
258–260 258–260 [25]
258–260 260–262 [19]
264–266 263–265 [19]
255–257 258–260 [19]
272–274 275–277 [19]
258–260 257–259 [20]
220–222 220–222 [29]
259–261 260–263 [19]
267–269 269–270 [25]
222–224 224–225 [23]
252–254 253–254 [22]
226–228 225–228 [30]
251–253 250–252 [23]
225–227 228–229 [22]
210–211 208–210 [21]
239–241 241–243 [23]
241–242 242–245 [31]
192–194 192–194 [23]
193–195 194–196 [21]
2
2-NO2–C6H4CHO
4-NO2-C6H4CHO
4-Cl–C6H4CHO
2,4-di–ClC6H3CHO
2-Cl–C6H4CHO
4-Me–C6H4CHO
4-MeO–C6H4CHO
4-HO–C6H4CHO
3-HO–C6H4CHO
4-Me2N–C6H4CHO
3
4
5
6
4g
4h
4i
7
8
9
4j
10
11
12
13
14
15
16
17
18
19
20
4k
4l
3-MeO-4-HO–C6H3CHO CN (3a)
4m
4n
4o
4p
3,4-di–MeO–C6H3CHO
Furan-2-carbaldehyde
CN (3a)
CN (3a)
Thiophen-2-carbaldehyde CN (3a)
C6H5CHO
CO2Et (3b) 4q
CO2Et (3b) 4r
CO2Et (3b) 4s
CO2Et (3b) 4t
CO2Et (3b) 4u
4-NO2–C6H4CHO
3-NO2–C6H4CHO
4-Cl–C6H4CHO
4-Me–C6H4CHO
Reaction conditions: substrates 1 mmol; water (5 mL); SM (10 mol %); stirred at 70 °C
a
Yields refer to the pure isolated products
123

Aqua one-pot, three-component synthesis of…
specified reaction times (Table 2, entries 1–20). The 3CR of substituted benzalde-
hydes bearing electron-withdrawing groups occurred in higher yields and shorter
reaction times than its electron-donating counterparts. The scope of the reaction was
further extended with a- and b-naphthol (5a and 5b) instead of 4-hydroxycoumaarin
(1) (Scheme 2).
The experiments were performed under the optimized reaction conditions, and
the corresponding 2-amino-4-aryl-4H-benzo[h]chromenes (6a–h) and 3-amino-1-
aryl-1H-benzo[f]chromenes (7a–j) were obtained in high isolated yields (Table 3).
From the results presented in Table 3, it is apparent that aldehydes containing both
electron-deficient and electron-rich substituents in the aromatic ring give high yields
of the desired amino-benzochromene products in reactions with malononitrile/ethyl
cyanoacetoacetate (3a and 3b) and nphthols (5a and 5b) in 25–65 min (Table 3).
In all cases, the filtrate containing the residual solvent and the catalyst obtained
upon filtration of the reaction mixture after completion of the reaction could be
reused in the preparation of the model product (4c) under the above-mentioned
optimized conditions. After each run, the resulting solid product was collected by
Table 3 Synthesis of 2-amino-4-aryl-4H-benzo[h]chromenes (6a–h) and 3-amino-1-aryl-1H-
benzo[f]chromenes (7a–l) in the presence of SM
Entry
Aldehyde
Cyano
compound/
Z
Product
Time
(min)
Yield
(%)a
M.p. (°C)
Found
Reported
references
1
C6H5CHO
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CO2Et (3b)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CN (3a)
CO2Et (3b)
CO2Et (3b)
CO2Et (3b)
6a
6b
6c
6d
6e
6f
50
30
45
25
50
40
35
55
60
45
45
40
40
45
40
50
55
60
65
50
92
94
91
94
92
93
94
91
92
92
93
95
93
89
94
92
93
88
93
91
205–207
241–243
211–213
231–233
197–198
245–247
186–188
199–201
278–280
182–184
188–190
204–206
242–243
257–259
244–246
184–186
244–246
167–168
189–190
202–204
210–211 [38]
242–243 [38]
210–212 [69]
232–234 [44]
202–204 [58]
247–249 [36]
188–189 [38]
198–200 [61]
280–282 [62]
182–183 [38]
189–190 [58]
206–210 [63]
242–244 [51]
270–272 [51]
246–248 [51]
184–187 [69]
244–245 [58]
166–168 [61]
188–190 [61]
202–204 [61]
2
4-O2NC6H4CHO
3-O2NC6H4CHO
4-ClC6H4CHO
4-MeC6H4CHO
4-HOC6H4CHO
4-MeOC6H4CHO
3-O2NC6H4CHO
C6H5CHO
3
4
5
6
7
6g
6h
7a
7b
7c
7d
7e
7f
8
9
10
11
12
13
14
15
16
17
18
19
20
4-O2NC6H4CHO
3-O2NC6H4CHO
4-ClC6H4CHO
4-BrC6H4CHO
4-MeC6H4CHO
4-OHC6H4CHO
4-MeOC6H4CHO
4-(Me)2NC6H4CHO
C6H5CHO
7g
7h
7i
7j
3-O2NC6H4CHO
3-ClC6H4CHO
7k
7l
Reaction conditions: 1 mmol of each reactant, water (5 mL), SM (10 mol %), 70 °C
a
Yields refer to the pure isolated products
123

H. Kiyani, M. Tazari
filtration. Substrates (1, 2c and 3a) were reacted together with the same molar ratios
in the filtrate-containing catalyst. The result showed a slight decrease of yield in the
first three runs (92, 89 and 86%), while in the fourth run the yield dropped to 79%,
probably due to the possibility of a reduction in the amounts of catalyst in the
recovery phase.
Mechanistically, we believe that this reaction goes via a Knoevenagel
condensation of aldehydes with active cyano compounds (3a and 3b) to provide
the corresponding electron-deficient arylidene nitrile intermediates D (Knoevenagel
adducts). On the other hand, the role of SM in aiding enol-keto tautomerism in
hydroxyl-containing compounds (1, 5a and 5b) to E is also envisioned. Then,
Michael-type addition of compounds 1, 5a and 5b to arylidene nitriles (D) takes
place to provide intermediates B and followed by intramolecular O-attack
heterocyclization (Thorpe–Ziegler type reaction) to provide intermediates
Scheme 3 A plausible reaction mechanism for the synthesis of 4a–u, 6a–h, and 7a–l
123

Aqua one-pot, three-component synthesis of…
Table 4 Comparative study of SM for the one-pot three-component synthesis of 4c and 6g
Entry Compounds
Catalyst/conditions
Time Yield References
(min) (%)
1
Borax/EtOH, reflux
Urea/H2O-EtOH, rt
120
180
10
76
97
93
88
85
[28]
[20]
[70]
[72]
[27]
[29]
[22]
[33]
[32]
[73]
[35]
[64]
2
3
PPI/H2O, reflux
4
KHP/H2O, 50 °C
180
30
5
Amberlyst A21/EtOH, rt
BF3ÁSiO2/solvent-free, 50 °C
HMTA/EtOH, reflux
Morpholine/H2O, reflux
Silica gel/absolute EtOH, rt
DMBA/EtOH, 60 °C
CTAB/H2O, r.t.
6
15–25 94
7
25
240
240
7
95
80
93
97
95
93
8
9
10
11
12
60
6
Fe3O4@SiO2–imid–PMAn/H2O,
reflux, US
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
Sodium acetate/H2O, US
Starch solution/50 °C
HCOONH4/H2O–EtOH, rt
SM/H2O, 70 °C
Basic alumina/H2O, 100 °C
Mg/Al hydrotalcite/140 °C, MW, SF 16
7
85
86
92
96
83
76
89
91
79
96
81
71
76
88
92
82
93
93
84
96
84
70
[62]
[19]
[34]
This work
[39]
[45]
[36]
[46]
[38]
[58]
[48]
[27]
[41]
[37]
[54]
[40]
[69]
[72]
[63]
[59]
[52]
[53]
60
60
15
180
I2/K2CO3/H2O, 100 °C
14[NaP5W30O110]/H2O, 100 °C
NaHCO3/grinding
60
H
195
90
TBAC/H2O, 100 °C
150
75
CeO2–CaO/H2O, 80 °C
Amberlyst A21/EtOH, rt
Nano-Na2CaP2O7/H2O, reflux
CTAB/H2O, US
360
300
150
30
Imidazole/EtOH, reflux
Nano-MgO/(PEG–H2O)
PPI/H2O, reflux
90
35
KHP/H2O, 50 °C
Na2CO3/H2O, US
285
12
PANDMAPF/different solvents, reflux
(NH4)2HPO4/H2O–EtOH, reflux
60
150
Amino-functionalized MCM-41/H2O, 120
70 °C
35
SM/H2O, 70 °C
35
94
This work
rt room temperature, PPI potassium phthalimide, KHP potassium hydrogen phthalate HMTA hexam-
ethylenetetramine, DMBA N,N-dimethylbenzylamine, CTAB cetyltrimethylammonium bromide, US
ultrasound, MW microwave, SF solvent-free, TBAC tetrabutylammonium chloride, PANDMAPF (4-
dimethylaminopyridine) functionalized polyacrylonitrile fiber catalyst, SM sodium malonate
123

H. Kiyani, M. Tazari
C which undergoes tautomerization and finally desired highly functionalized
chromenes (4a–u, 6a–h and 7a–j) are formed (Scheme 3).
A comparative study on the catalytic performance of SM with other reported
catalysts for the one-pot, three-component synthesis of 4c and 6g as typical
examples are shown in Table 4. This comparison clearly indicates that the current
work is better or comparable with others in terms of environmental safety, yields
and reaction times. Furthermore, this method requires only sodium malonate as base
and there is no need for the synthesis of the catalyst, ball-milling, microwave
heating or ultrasound irradiation.
Conclusions
In conclusion, this study describes the first report on a one-pot, 3CR, sodium
malonate-catalyzed synthesis of various dihydropyrano[3,2-c]chromenes, 2-amino-
4-aryl-4H-benzo[h]chromenes and 3-amino-1-aryl-1H-benzo[f]chromenes. The pre-
sent method provided an attractive alternative to the existing procedures for the
synthesis of such significant heterocyclic compounds. The key advantages of the
present method are high yields, no need for catalyst synthesis, operational
simplicity, no column chromatography, the absence of tedious separation proce-
dures, clean reaction profiles, the use of an inexpensive and environmentally benign
solvent, and the reusability of the reaction medium.
Acknowledgement The authors would like to Damghan University for its partial financial support.
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