One-pot three-component condensation of β-naphthol with arylaldehydes and Meldrum's acid: Synthesis of 1-aryl-1,2-dihydro-benzo[f]chromen-3-ones

Article abstract of DOI:10.3184/174751917X14902201357374

An efficient and simple method for the synthesis of 1-aryl-1,2-dihydro-benzo[f]chromen-3-ones via a one-pot three-component reaction of β-naphthol, arylaldehydes and Meldrum's acid with Et₃N as a base in CH₃CN under reflux is reporte

Full text of DOI:10.3184/174751917X14902201357374

250 RESEARCH PAPER
VOL. 41 APRIL, 250–252
JOURNAL OF CHEMICAL RESEARCH 2017
One-pot three-component condensation of β-naphthol with arylaldehydes and
Meldrum’s acid: synthesis of 1-aryl-1,2-dihydro-benzo[f]chromen-3-ones
Hossein Mehrabi*, Faezeh Najafian-Ashrafi and Reza Ranjbar-Karimi
Department of Chemistry, Vali-e-Asr University of Rafsanjan, 77176 Rafsanjan, Iran
An efficient and simple method for the synthesis of 1-aryl-1,2-dihydro-benzo[f]chromen-3-ones via a one-pot three-component reaction of
β-naphthol, arylaldehydes and Meldrum’s acid with Et3N as a base in CH3CN under reflux is reported. All the products were obtained in
good to excellent yields and their structures were established from their spectroscopic data.
Keywords: multi-component reactions, β-naphthol, Meldrum’s acid, 1-aryl-1,2-dihydro-benzo[f]chromen-3-ones
Coumarin and its derivatives have a varied biological activity as
analgesics,1,2 anticancer,3,4 antitumour,5 antibacterial,6 antifungal,7
anticoagulant8 and antiinflammatory9 agents, as well as being
specific inhibitors of α-chymotripsin,10 human leukocyte elastase,11
platelet aggregation,12,13 and HIV-1 protease.14 In addition, these
compounds are being used as additives in food and cosmetics,15
and as fluorescent agents and in laser dye16,17 applications.
Coumarins are often synthesised by the Claisen rearrangement,
the Perkin reaction, the Pechmann reaction and the Knoevenagel
condensation.18 This report deals with a new and simple synthesis
of benzo[f]chromen-3-one derivatives.
It is known that the Meldrum’s acid undergoes the standard
Knoevenagel condensation with aromatic and heteroaromatic
aldehydes to furnish the corresponding arylidene derivatives, which
are versatile substrates for various reactions.19,20 They are useful
intermediates for cycloaddition reactions and for the synthesis of
heterocyclic compounds with potential pharmacological activity.21
With this background in mind, we investigated a one-pot three-
component condensation reaction of β-naphthol, arylaldehydes
and Meldrum’s acid, with Et3N as a base in CH3CN under reflux
for an appropriate time to afford substituted benzo[f]chromen-3-
ones.
concluded that the electronic nature of the substituents has no
significant effect on this reaction.
1
The products were characterised by H NMR, 13C NMR, IR,
CHN analysis and melting points. Thus, the 1H NMR spectrum of
compound 4a showed two double doublets for the two hydrogens
of a methylene group at δ = 3.16 and 3.24 ppm. The methine
proton was discernible as a double doublet at δ = 4.97 ppm and the
aromatic protons resonated in the region δ = 7.12–7.89 ppm. The
13C NMR spectrum of compound 4a exhibited 17 distinct signals
in agreement with the proposed structure. In the IR spectrum,
the ester carbonyl absorption was observed at 1766 cm−1. Partial
assignments of these resonances for the other products are given in
the experimental section.
The possible mechanism for the synthesis of 1-aryl-1,2-dihydro-
benzo[f]chromen-3-ones 4 is illustrated in Scheme 2. This
conversion involves the initial reaction of the arylaldehyde 2 with
Meldrum’s acid 3 to form the arylidene Meldrum’s acid A. The
arylidene Meldrum’s acid and β-naphthol produce the intermediate
B by a Michael addition, and this intermediate then cyclises,
eliminating acetone and carbon dioxide, in stages, affording the
final product 4.
In summary, this work describes an efficient and simple
approach for a one-pot multi-component synthesis of 1-aryl-1,2-
Results and discussion
The optimised conditions for the condensation of Meldrum’s acid
with benzaldehyde and β-naphthol are Meldrum’s acid (1.0 mmol),
benzaldehyde (1.0 mmol), β-naphthol (1.2 mmol) and two drops of
Et3N in CH3CN (8 mL) under reflux conditions. To establish the
efficiency and scope of this novel transformation, we performed
the reaction with a variety of substituted benzaldehydes under
reflux conditions (Scheme 1, Table 1).
As shown in Table 1, a series of 1-aryl-1,2-dihydro-benzo[f]
chromen-3-one derivatives 4a–i bearing electron-withdrawing
groups (for example, halide) or electron-donating groups (for
example, methyl and methoxy) were synthesised by the reaction
of Meldrum’s acid with 1 and 2 to give the corresponding products
4a–i in good yields under the same reaction conditions. We
Table 1 Synthesis of 1-aryl-1,2-dihydro-benzo[f]chromen-3-ones
Product
4a
4b
4c
4d
4e
R
H
Time/h
10.0
5.0
9.0
7.0
Yield/%a
83
80
85
65
97
4-Me
4-OMe
4-Br
4-F
4.0
4f
4g
4h
4i
4-CF3
2-Cl
3-Cl
4-Cl
6.0
5.0
8.0
8.0
95
97
70
75
aIsolated yields.
R
O
OH
H
O
O
Et3N
CH3CN, Reflux
O
+
+
O
R
O
O
1
3
a-i
2
4
Scheme 1
* Correspondent. E-mail: mehraby_h@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2017 251
O
O
O
O
O
Et3N
H
O
O
- H2O
O
O
R
A
3
2
R
OH
Michael
Addition
1
R
R
O
O
O
H
- CO2
- CH3COCH3
O
O
O
O
4
B
Scheme 2
4c: M.p. 123–125 °C; IR (KBr) (υ cm−1): 2964, 1762, 1581, 1463,
1438, 1417, 1137; 1H NMR (300 MHz, CDCl3): δ 3.16 (dd, J = 2.8 and
15.2 Hz, 1H, CH2), 3.19 (dd, J = 5.7 and 15.2 Hz, 1H, CH2), 3.73 (S,
3H, OCH3), 4.92 (dd, J = 2.8 and 5.7 Hz, 1H, CH), 6.79–7.89 (m, 10H,
Ar); 13C NMR (75 MHz, CDCl3): δ 36.8, 37.6, 55.2, 114.5, 117.5, 118.0,
123.1, 125.2, 127.4, 128.0, 128.7, 129.8, 130.9, 131.1, 132.5, 149.6, 158.9,
167.2. Anal. calcd for C20H16O3 (304.34): C, 78.93; H, 5.30; found: C,
79.17; H, 5.34%.
dihydro-benzo[f]chromen-3-ones, by use of Meldrum’s acid,
arylaldehydes and β-naphthol. The method has very attractive
features, for example, giving good to excellent yields, under
simple reaction conditions, with an easy work up. Moreover,
participation of Meldrum’s acid makes this process highly
efficient.
Experimental
4d: M.p. 160–162 °C; IR (KBr) (υ cm−1): 1766, 1486, 1253, 1224,
1210, 1187; 1H NMR (300 MHz, CDCl3): δ 3.13 (dd, J = 1.2 and 18.2
Hz, 1H, CH2), 3.22 (dd, J = 6.4 and 18.2 Hz, 1H, CH2), 4.92 (dd, J = 1.2
and 6.4 Hz, 1H, CH), 6.98–8.28 (m, 10H, Ar); 13C NMR (75 MHz,
CDCl3): δ 37.4, 37.6, 117.6, 117.9, 123.1, 125.2, 126.8, 127.3, 128.6,
129.7, 129.7, 131.0, 131.0, 137.5, 137.5, 148.6, 167.2 Anal. calcd for
C19H13BrO2 (353.21): C, 64.61; H, 3.71; found: C, 64.39; H, 3.68%.
4e: M.p. 128–130 °C; IR (KBr) (υ cm−1): 3075, 2930, 1759, 1510,
1424, 1337, 1290, 1173; 1H NMR (300 MHz, CDCl3): δ 3.16 (dd, J = 1.9
and 15.7 Hz, 1H, CH2), 3.22 (dd, J = 6.4 and 15.7 Hz, 1H, CH2), 4.96
(dd, J = 1.9 and 6.4 Hz, 1H, CH), 6.93–7.90 (m, 10H, Ar); 13C NMR
(75 MHz, CDCl3): δ 36.9, 37.5, 115.9, 116.2, 117.4, 122.8, 125.3, 127.5,
128.6, 128.8, 130.1, 130.8, 131.1, 136.2, 149.7, 160.4, 166.9. Anal. calcd
for C19H13FO2 (292.30): C, 78.07; H, 4.48; found: C, 78.26; H, 4.51%.
4f: M.p. 121–123 °C; IR (KBr) (υ cm−1): 3062, 1772, 1516, 1438, 1417,
1209, 1177, 1130, 1083; 1H NMR (300 MHz, CDCl3): δ 3.17 (dd, J = 2.1
and 15.8 Hz, 1H, CH2), 3.28 (dd, J = 6.8 and 15.8 Hz, 1H, CH2), 5.02
(dd, J = 2.1 and 6.8 Hz, 1H, CH), 7.26–7.94 (m, 10H, Ar); 13C NMR
(75 MHz, CDCl3): δ 37.1, 37.4, 116.6, 117.5, 122.7, 125.4, 126.3, 127.4,
127.7, 128.9, 129.7, 130.1, 130.4, 130.7, 131.1, 144.5, 149.9, 166.5. Anal.
calcd for C20H13F3O2 (342.32): C, 70.17; H, 3.83; found: C, 70.31; H,
3.86%.
All chemicals were purchased from Aldrich and Merck with high
quality, and were used without any purification. All melting points
were obtained by Bamslead Electrothermal 9200 apparatus and are
uncorrected. The reactions were monitored by TLC and all yields refer
1
to isolated products. H NMR and 13C NMR spectra were recorded
in CDCl3 on a Bruker 300 MHz spectrometer. Infrared spectra were
recorded on a Bruker FTIR Equinox-55 spectrophotometer in KBr with
absorption in cm−1. Elemental analyses were performed using a Carlo
Erba EA 1108 instrument. All products were characterised by their
spectral and physical data.
Synthesis of 1-aryl-1,2-dihydro-benzo[f]chromen-3-one derivatives
(4a–i); general procedure
A mixture of the appropriate arylaldehyde 2 (1.0 mmol), Meldrum’s
acid 3 (1.0 mmol) and β-naphthol 1 (1.2 mmol) was stirred in CH3CN
(8 mL) in the presence of two drops of Et3N under reflux conditions for
an appropriate time. After reaction completion, determined by TLC,
the solvent was removed under reduced pressure, and the resulting
crude product was recrystallised from ethanol to give the pure
compounds 4a–i.
4a: M.p. 110–112 °C; IR (KBr) (υ cm−1): 3055, 2930, 1766, 1515,
1425, 1223, 1141, 1074; 1H NMR (300 MHz, CDCl3): δ 3.16 (dd, J = 2.4
and 15.9 Hz, 1H, CH2), 3.24 (dd, J = 6.3 and 15.9 Hz, 1H, CH2), 4.97
(dd, J = 2.4 and 6.3 Hz, 1H, CH), 7.12–7.89 (m, 11H, Ar); 13C NMR
(75 MHz, CDCl3): δ 37.4, 37.6, 117.5, 117.5, 125.2, 126.9, 127.4, 127.5,
128.7, 129.2, 129.9, 131.0, 131.1, 140.5, 149.8, 167.1. Anal. calcd for
C19H14O2 (274.31): C, 83.19; H, 5.14; found: C, 83.32; H, 5.09%.
4b: M.p. 164–166 °C; IR (KBr) (υ cm−1): 2924, 1769, 1512, 1222,
1186, 1175; 1H NMR (300 MHz, CDCl3): δ 2.28 (S, 3H, CH3), 3.14 (dd,
J = 2.3 and 15.7 Hz, 1H, CH2), 3.21 (dd, J = 6.2 and 15.7 Hz, 1H, CH2),
4.93 (dd, J = 2.3 and 6.2 Hz, 1H, CH), 7.00–7.88 (m, 10H, Ar); 13C
NMR (75 MHz, CDCl3): δ 21.0, 37.2, 37.5, 117.5, 117.8, 123.1, 125.2,
126.8, 127.4, 128.7, 129.8, 129.9, 131.0, 131.0, 137.2, 137.5, 149.7, 167.2.
Anal. calcd for C20H16O2 (288.34): C, 83.31; H, 5.59; found: C, 83.52;
H, 5.63%.
4g: M.p. 157–159 °C; IR (KBr) (υ cm−1): 3073, 1770, 1587, 1515, 1470,
1
1442, 1419, 1274, 1241, 1176, 1159, 1133, 1085; H NMR (300 MHz,
CDCl3): δ 3.17 (dd, J = 3.2 and 15.9 Hz, 1H, CH2), 3.24 (dd, J = 5.8 and
15.9 Hz, 1H, CH2), 5.45 (dd, J = 3.2 and 5.8 Hz, 1H, CH), 6.71–7.92 (m,
10H, Ar); 13C NMR (75 MHz, CDCl3): δ 34.4, 35.3, 116.7, 117.4, 122.9,
125.4, 127.7, 127.7, 128.2, 128.7, 129.0, 130.2, 130.3, 130.7, 131.1, 132.8,
137.4, 150.4, 166.8. Anal. calcd for C19H13ClO2 (308.76): C, 73.91; H,
4.24; found: C, 74.06; H, 4.27%.
4h: M.p. 172–174 °C; IR (KBr) (υ cm−1): 3041, 1784, 1586, 1562,
1412, 1417, 1240, 1219, 1177, 1124; 1H NMR (300 MHz, CDCl3): δ 3.13
(dd, J = 2.1 and 15.8 Hz, 1H, CH2), 3.21 (dd, J = 6.5 and 15.8 Hz, 1H,
CH2), 4.94 (dd, J = 2.1 and 6.5 Hz, 1H, CH), 7.00–7.92 (m, 10H, Ar);
13C NMR (75 MHz, CDCl3): δ 37.3, 37.3, 116.7, 117.5, 122.8, 125.1,

252 JOURNAL OF CHEMICAL RESEARCH 2017
6
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4i: M.p. 114–116 °C; IR (KBr) (υ cm−1): 3063, 1779, 1515, 1490, 1464,
1436, 1250, 1174, 1136, 1084; 1H NMR (300 MHz, CDCl3): δ 3.14 (dd,
J = 1.9 and 15.7 Hz, 1H, CH2), 3.24 (dd, J = 6.7 and 15.7 Hz, 1H, CH2),
4.95 (dd, J = 1.9 and 6.7 Hz, 1H, CH), 7.06–7.91 (m, 10H, Ar);13C NMR
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128.8, 129.4, 130.2, 130.8, 131.1, 133.5, 138.9, 149.8, 166.7. Anal. calcd
for C19H13ClO2 (308.76): C, 73.91; H, 4.24; found: C, 74.13; H, 4.27%.
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Received 1 February 2017; accepted 9 March 2017
Paper 1704578
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