Reusable melamine trisulfonic acid-catalyzed three-component synthesis of 7-alkyl-6H,7H-naphtho[1′,2′:5,6]pyrano[3,2-c]chromen-6-ones

Article abstract of DOI:10.1007/s00706-010-0427-9

An efficient synthesis of 7-alkyl-6H,7H-naphtho[1′,2′:5,6] pyrano[3,2-c]chromen-6-ones by three-component condensation reaction of β-naphthol, aromatic aldehydes, and 4-hydroxycoumarin under solvent-free conditions in good to excellent yields and short re

Full text of DOI:10.1007/s00706-010-0427-9

Monatsh Chem (2011) 142:163–167
DOI 10.1007/s00706-010-0427-9
ORIGINAL PAPER
Reusable melamine trisulfonic acid-catalyzed three-component
synthesis of 7-alkyl-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-ones
•
Weiwei Ma Xiao Wang Fulin Yan
•
•
•
Liqiang Wu Yingling Wang
Received: 13 June 2010 / Accepted: 18 November 2010 / Published online: 21 December 2010
Ó Springer-Verlag 2010
Abstract An efficient synthesis of 7-alkyl-6H,7H-naphtho-
[10,20:5,6]pyrano[3,2-c]chromen-6-ones by three-compo-
nent condensation reaction of b-naphthol, aromatic
aldehydes, and 4-hydroxycoumarin under solvent-free con-
ditions in good to excellent yields and short reaction times
using reusable melamine trisulfonic acid as solid acid cata-
lyst has been investigated.
reactions, such as acetylation of alcohols, phenols, and
amines [19], oxathioacetalyzation of aldehydes [20], and
methoxymethylation of alcohols [21]. This catalyst is safe,
easy to handle, and environmentally benign, and presents
fewer disposal problems. Melamine trisulfonic acid as a
solid acid catalyst is prepared from reaction of melamine
with neat chlorosulfonic acid at room temperature.
Herein, we describe a simple and efficient protocol for
rapid preparation of 7-alkyl-6H,7H-naphtho[10,20:5,6]pyr-
ano[3,2-c]chromen-6-ones using a catalytic amount of
recyclable melamine trisulfonic acid under solvent-free
conditions (Scheme 1). To the best of our knowledge, there
is only one previous account describing this quinoidal
system [22].
Keywords Naphtho[10,20:5,6]pyrano[3,2-c]chromen-6-one ꢀ
Melamine trisulfonic acid ꢀ Acidity ꢀ Catalysis ꢀ
Solvent-free
Introduction
Chromenes constitute a major class of naturally occurring
compounds [1–7], and interest in their chemistry continues
unabated because of their wide range of biological and
therapeutic properties such as antioxidant [8, 9], antibacte-
rial [10, 11], antirhinovirus [12], cytotoxic [13], anticancer
[14, 15], antimicrobial [16, 17], and antihypertensive
activity [18]. Considering the above reports, development of
new and simple synthetic methods for efficient preparation
of new chromenes is therefore an interesting challenge.
Recently, melamine trisulfonic acid (MTSA) has
emerged as a promising solid acid catalyst for acid-catalyzed
Results and discussion
To choose optimum conditions, first, the effect of tempera-
ture on the rate of the reaction was studied for the preparation
of 7-phenyl-6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]chro-
men-6-one by three-component condensation reaction
of b-naphthol, benzaldehyde, and 4-hydroxycoumarin in
presence of 2 mol% melamine trisulfonic acid under sol-
vent-free conditions (Table 1). At 120 °C, the reaction
proceeded smoothly and gave short reaction time and high
yield. Therefore, we kept the reaction temperature at 120 °C.
Next, the study set out to determine the optimal amount
of MTSA; the reaction was carried out by varying amount
of the catalyst (Table 2). Maximum yield was obtained
with 2 mol% of the catalyst. Further increase in amount of
MTSA in the mentioned reaction did not have any signif-
icant effect on product yield.
W. Ma ꢀ X. Wang ꢀ F. Yan ꢀ L. Wu (&)
School of Pharmacy, Xinxiang Medical University,
Xinxiang 453003, Henan, China
e-mail: wliq1974@sohu.com
Y. Wang
School of Basic Medicine, Xinxiang Medical University,
Xinxiang 453003, Henan, China
Using these optimized reaction conditions, the scope and
efficiency of these procedures were explored for synthesis of
123

164
W. Ma et al.
9
Scheme 1
10
11
8
R1'
O
7b
O
O
6a
7a
OH
+ RCHO
O5
7
6
MTSA
11a
12
+
4a
14
13a O
14b
neat, 120 °C
14a
4
13
OH
1
3
2
4
3
2
1
Table 3 Preparation of 7-alkyl-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-ones
Table 1 Temperature optimization for the synthesis of 7-phenyl-
6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]chromen-6-one
Yield (%)a
Entry
Temperature (°C)
Time (h)
Yield (%)a
Entry
R
Time (h)
Product
1
25
50
8
0
34
38
42
56
63
72
82
89
88
88
1
2
3
4
5
6
7
8
C6H5
1
4a
4b
4c
4d
4e
4f
89 (85, 82, 76)b
2
5
4-Cl-C6H4
4-F-C6H4
1
88
84
91
89
83
82
81
3
60
3
1
4
70
3
4-Me-C6H4
4-NO2-C6H4
3-NO2-C6H4
2,4-Cl2-C6H3
3,4-Cl2-C6H3
0.5
1
5
80
3
6
90
1.5
1.5
1
1.5
1.5
1.5
7
100
110
120
130
140
4g
4h
8
9
1
Reaction conditions: b-naphthol (1 mmol), aldehyde (1 mmol),
4-hydroxycoumarin (1 mmol), MTSA (0.02 mmol); 120 °C; neat
10
11
1
a
1
Isolated yields
b
Yields after three times of catalyst recovery
Reaction conditions: b-naphthol (1 mmol), benzaldehyde (1 mmol),
4-hydroxycoumarin (1 mmol), MTSA (0.02 mmol); neat
a
1H nuclear magnetic resonance (NMR) spectra of the reac-
tion mixture showed a combination of starting materials
and numerous products, and the yield of the expected
product was very poor. This methodology offers significant
improvements with regard to the scope of this transforma-
tion, simplicity in operation, and green aspects by avoiding
expensive or corrosive catalysts. All of the products 4
exhibited a singlet in their 1H spectra at d = 5.71–6.11 ppm
for H-7, and a distinguishing peak at d = 34.3–36.4 ppm
for C-7 in their 13C NMR spectra. The resonances of car-
bonyl groups in the 13C NMR spectrum of 4 appeared at
d = 172.9–176.8 ppm. To assign the observed signals to
individual protons and carbons, we performed two-dimen-
sional (2D) NMR studies [1H–1H correlation spectroscopy
(COSY), heteronuclear multiple-bond correlation (HMBC),
heteronuclear single quantum correlation (HSQC)] for
compound 4e (see ‘‘Experimental’’ part).
Isolated yields
Table 2 Optimization of the catalyst amount for the synthesis of
7-phenyl-6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]chromen-6-one
Entry
MTSA (mol%)
Time (h)
Yield (%)a
1
2
3
4
5
6
7
8
0
8
0
45
61
79
89
89
88
89
0.5
1
2
1.5
1.5
1
1.5
2
2.5
3
1
1
3.5
1
Reaction conditions: b-naphthol (1 mmol), benzaldehyde (1 mmol),
4-hydroxycoumarin (1 mmol); 120 °C; neat
a
Isolated yields
The reusability of the catalyst was tested in the synthesis
of 7-phenyl-6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]chro-
men-6-ones. The catalyst was recovered after each run,
washed with CH2Cl2, dried in an oven at 100 °C for
30 min prior to use, and tested for its activity in the sub-
sequent run with no fresh catalyst added. The catalyst was
tested for three runs. It was seen that the catalyst displayed
very good reusability (Table 3, entry 1).
a wide variety of 7-alkyl-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-ones. The results are summarized in
Table 3. As shown in Table 3, the direct three-component
reaction worked well with a variety of aryl aldehydes
including those bearing electron-withdrawing and electron-
donating groups such as Me, Cl, F, and NO2, and the desired
compounds were obtained in high to excellent yields. When
this reaction was carried out with aliphatic aldehydes such as
butanal or pentanal, thin-layer chromatography (TLC) and
The suggested mechanism of the MTSA-catalyzed
transformations is shown in Scheme 2. The reaction likely
123

Reusable melamine trisulfonic acid-catalyzed three-component synthesis
165
Scheme 2
R
OH
OH
R
OH
O
-H2O
RCHO
H
5
1
3
R
OH
O
O
R
O
O
H
O
O
O
HO
OH
OH2
6
R
O
O
-H2O
-H
O
4
Table 4 Comparison of the effect of catalysts in the synthesis of
7-phenyl-6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]chromen-6-one
proceeds via initial formation of ortho-quinone methide 5.
The oxonium species 6 is then formed on reaction with
4-hydroxycoumarin, which then undergoes dehydration to
afford the desired product 4. In b-naphthol the electron
density at the benzylic C-1 position (which is in conjuga-
tion with the aromatic ring) is higher than that at the C-3
position. Thus, regioselective formation of the ortho-qui-
none methide from this compound involving the C-1 and
C-2 positions is favored. In simple phenolic compounds
and 1-naphthol (which are weaker nucleophiles compared
with b-naphthol) the electron density at the ortho-position
of the hydroxyl group is not sufficient for the reaction of
these compounds with the aldehydes, leading to the for-
mation of the corresponding ortho-quinone methides.
To emphasize the effect of the catalyst, the model reac-
tion of b-naphthol, benzaldehyde, and 4-hydroxycoumarin
was investigated using various catalysts. All the reactions
were run under the same conditions, and similar amounts of
catalysts (2 mol%) were used. As shown in Table 4, satis-
factory results were obtained only with MTSA.
Entry
Catalyst
Yield (%)a
1
2
3
4
5
6
H2SO4
NaHSO3
NaHSO4
AlCl3
25
40
72
58
69
89
I2
MTSA
Reaction conditions: b-naphthol (1 mmol), benzaldehyde (1 mmol),
4-hydroxycoumarin (1 mmol), catalyst (0.02 mol); 120 °C; neat
a
Isolated yields
successfully recovered and recycled at least for three runs
without significant loss in activity.
Experimental
NMR spectra were determined on a Fourier-transform (FT)-
NMR Avance 400 spectrometer in CDCl3 or dimethyl
sulfoxide (DMSO)-d6 and are expressed in d values relative
to tetramethylsilane; coupling constants (J) are measured in
Hz. Mass spectra were recorded on a Finnigan LCQ
Advantage mass spectrometer. Elemental analyses were
recorded on a Vario-III elemental analyzer. Melting
points were determined on a XT-4 binocular microscope.
In summary, an efficient protocol for one-pot preparation
of 7-alkyl-6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]chromen-
6-ones by three-component condensation reaction of
b-naphthol, aromatic aldehydes, and 4-hydroxycoumarin
using reusable MTSA as catalyst is described. The reactions
were carried out under thermal solvent-free conditions with
short reaction time and produced the corresponding products
in good to excellent yields. Also, the catalyst could be
123

166
W. Ma et al.
(t, 1H, J = 8.0 Hz, ArH), 7.50–7.39 (m, 7H, ArH), 6.90 (t,
2H, J = 8.4 Hz, ArH), 6.11 (s, 1H, CH) ppm; 13C NMR
(DMSO-d6, 100 MHz): d = 173.5, 165.6, 156.2, 153.0,
147.4, 139.5, 133.5, 131.8, 130.9, 130.0, 129.9, 129.7,
128.6, 127.5, 126.0, 125.5, 125.3, 123.9, 123.3, 117.4,
117.3, 116.5, 115.3, 115.1, 100.0, 35.5 ppm; MS (ESI):
m/z = 395 ([M ? H]?).
Commercially available reagents were used throughout
without further purification unless otherwise stated.
Preparation of MTSA catalyst
A 250-cm3 suction flask charged with 5 cm3 chlorosulfonic
acid (75.2 mmol) was equipped with a gas inlet tube for
conducting HCl gas over an adsorbing solution. Melamine
(3.16 g, 25.07 mmol) was added in small portions over a
period of 30 min at room temperature. HCl gas evolved
from the reaction vessel immediately (Scheme 3). After
completion of the addition of melamine, the mixture was
shaken for 30 min; meanwhile, the residual HCl was
removed by suction. Melamine trisulfonic acid (7.7 g,
85%) was obtained as a white solid.
7-(4-Methylphenyl)-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-one (4d, C27H18O3)
1
White powder; m.p.: 230–231 °C; H NMR (DMSO-d6,
400 MHz): d = 8.17–8.14 (m, 1H, ArH), 8.06–8.01 (m,
2H, ArH), 7.90 (d, 1H, J = 7.6 Hz, ArH), 7.72–7.68 (m,
2H, ArH), 7.54–7.45 (m, 4H, ArH), 7.26 (d, 2H,
J = 8.0 Hz, ArH), 7.01 (d, 2H, J = 8.0 Hz, ArH), 5.71
(s, 1H, CH), 2.14 (s, 3H) ppm; 13C NMR (DMSO-d6,
100 MHz): d = 172.9, 160.7, 154.5, 152.4, 147.0, 141.1,
136.4, 133.1, 131.8, 130.8, 130.1, 129.4, 129.1, 128.8,
127.8, 125.8, 125.1, 123.9, 123.1, 117.6, 117.0, 116.8,
114.1, 105.1, 35.9, 20.9 ppm; MS (ESI): m/z = 391
([M ? H]?).
General procedure for the preparation of 4
A mixture of b-naphthol (1 mmol), aldehyde (1 mmol),
4-hydroxycoumarin (1 mmol), and MTSA (0.02 mmol)
was heated at 120 °C for an appropriate time (TLC). After
completion, the reaction mixture was washed with 15 cm3
water and the residue recrystallized from EtOH to afford
the pure product 4. Aqueous washings were collected and
evaporated under reduced pressure. After removal of the
water, MTSA was recovered.
7-(4-Nitrophenyl)-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-one (4e, C26H15NO5)
White powder; m.p.: 257–258 °C; 1H NMR (CDCl3,
400 MHz): d = 8.17 (d, 1H, J = 8.0 Hz, H-1), 8.05 (d,
2H, J = 8.8 Hz, H-30, 50), 7.91–7.84 (m, 3H, H-3, 8, 11),
7.68–7.62 (m, 3H, H-9, 20, 60), 7.50–7.38 (m, 5H, H-2, 4,
10, 12, 13), 6.19 (s, 1H, H-7) ppm; 13C NMR (CDCl3,
100 MHz): d = 176.8 (C-6), 160.2 (C-14a), 153.0 (C-4a),
150.8 (C-10), 147.5 (C-7b), 146.7 (C-40), 133.7 (C-9), 131.9
(C-13a), 130.8 (C-11a), 130.4 (C-8), 129.4 (C-20, 60), 128.8
(C-3), 127.8 (C-2), 126.0 (C-1), 125.8(C-13), 125.6 (C-4),
123.8 (C-30, 50), 123.5 (C-11), 123.2 (C-14b), 117.5 (C-10),
116.6 (C-12), 116.0 (C-7a), 98.9 (C-6a), 36.3 (C-7) ppm;
MS (ESI): m/z = 422 ([M ? H]?).
7-Phenyl-6H,7H-naphtho[10,20:5,6]pyrano[3,2-c]-
chromen-6-one (4a)
White powder; m.p.: 281–282 °C (Ref. [22]: 275 °C).
7-(4-Chlorophenyl)-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-one (4b, C26H15ClO3)
White powder; m.p.: 267–268 °C; 1H NMR (CDCl3,
400 MHz): d = 8.20 (d, 1H, J = 7.6 Hz, ArH), 7.97 (d,
1H, J = 8.0 Hz, ArH), 7.91–7.86 (m, 2H, ArH), 7.69–7.40
(m, 8H, ArH), 7.18 (d, 2H, J = 8.4 Hz, ArH), 6.11 (s, 1H,
CH) ppm; 13C NMR (DMSO-d6, 100 MHz): d = 174.6,
160.7, 154.8, 152.5, 147.0, 142.9, 133.3, 131.9, 130.8,
130.7, 130.4, 129.1, 128.8, 127.9, 125.9, 125.2, 123.9,
132.2, 117.7, 117.0, 116.2, 114.1, 104.5, 35.8 ppm; MS
(ESI): m/z = 411 ([M ? H]?).
7-(3-Nitrophenyl)-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-one (4f, C26H15NO5)
White powder; m.p.: 249–250 °C; 1H NMR (CDCl3,
400 MHz): d = 8.17–8.12 (m, 2H, ArH), 8.01–7.85 (m,
5H, ArH), 7.63–7.58 (m, 2H, ArH), 7.52–7.35 (m, 5H, ArH),
5.97 (s, 1H, CH) ppm; 13C NMR (CDCl3, 100 MHz):
d = 176.2, 161.4, 155.4, 152.7, 148.5, 147.3, 145.1,
135.0, 132.5, 131.9, 130.6, 130.4, 129.3, 128.8, 127.7,
125.6, 124.4, 123.4, 123.1, 122.9, 122.2, 117.1, 116.8,
115.0, 114.1, 103.8, 36.3 ppm; MS (ESI): m/z = 422
([M ? H]?).
7-(4-Fluorophenyl)-6H,7H-naphtho[10,20:5,6]pyrano-
[3,2-c]chromen-6-one (4c, C26H15FO3)
White powder; m.p.: 253–254 °C; 1H NMR (CDCl3,
400 MHz): d = 8.20 (d, 1H, J = 7.6 Hz, ArH), 7.98 (d,
1H, J = 8.0 Hz, ArH), 7.87 (t, 2H, J = 9.6 Hz, ArH), 7.67
Scheme 3
NHSO3H
NH2
neat
r.t.
N
N
+ 3HCl
N
N
ClSO3H (3 eq.)
+
HO3SHN
N
NHSO3H
H2N
N
NH2
123

Reusable melamine trisulfonic acid-catalyzed three-component synthesis
167
7-(2,4-Dichlorophenyl)-6H,7H-naphtho[10,20:5,6]-
pyrano[3,2-c]chromen-6-one (4g, C26H14Cl2O3)
2. Malquichagua Salazar KJ, Delgado Paredes GE, Lluncor LR,
Young MCM, Kato MJ (2005) Phytochemistry 66:573
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chemistry 37:1593
1
White powder; m.p.: 267–268 °C; H NMR (DMSO-d6,
400 MHz): d = 8.18 (d, 1H, J = 7.2 Hz, ArH), 8.04 (d,
2H, J = 8.0 Hz, ArH), 7.97 (d, 1H, J = 7.2 Hz, ArH),
7.73–7.67 (m, 2H, ArH), 7.52–7.48 (m, 6H, ArH), 7.26 (m,
1H, ArH), 6.02 (s, 1H, CH) ppm; 13C NMR (CDCl3,
100 MHz): d = 175.5, 161.6, 155.0, 152.6, 147.3, 143.2,
132.0, 131.8, 131.0, 129.5, 128.8, 128.6, 128.5, 128.4,
127.4, 126.9, 125.3, 124.2, 123.6, 122.7, 116.9, 116.7,
116.6, 114.5, 105.2, 36.4 ppm; MS (ESI): m/z = 445
([M ? H]?).
4. Numata A, Kanbara S, Takahashi C, Fujiki R, Yoneda M, Usami
Y, Fujita E (1992) Phytochemistry 31:1209
5. Kulkarni MM, Nagasampagi BA, Deshpande SG, Sharma RN
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7-(3,4-Dichlorophenyl)-6H,7H-naphtho[10,20:5,6]-
pyrano[3,2-c]chromen-6-one (4h, C26H14Cl2O3)
11. El-Saghier AMM, Naili MB, Rammash BK, Saleh NA, Kreddan
KM (2007) Arkivoc (xvi):83
White powder; m.p.: 256–257 °C; 1H NMR (CDCl3,
400 MHz): d = 8.20 (dd, 1H, J = 1.2, 7.6 Hz, ArH),
7.93–7.86 (m, 3H, ArH), 7.70–7.66 (m, 1H, ArH),
7.55–7.36 (m, 7H, ArH), 7.29 (m, 1H, ArH), 6.07 (s, 1H,
ArH) ppm; 13C NMR (CDCl3, 100 MHz): d = 173.5,
161.5, 155.3, 152.7, 147.3, 143.2, 132.6, 132.4, 131.8,
131.1, 130.8, 130.4, 130.3, 130.1, 128.7, 128.2, 127.7,
125.6, 124.3, 123.3, 122.8, 116.9, 116.8, 115.3, 114.2,
104.1, 35.8 ppm; MS (ESI): m/z = 445 ([M ? H]?).
12. Conti C, Desideri N (2009) Bioorg Med Chem 17:3720
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Acknowledgments We are pleased to acknowledge the financial
support by Henan Research Program of Foundation and Advanced
Technology (no. 102300410101).
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