Synthesis and Bioassay of Dihydropyrano[3,2-b]chromenediones

Article abstract of DOI:10.1002/jhet.2289

Ytterbium perfluorooctanoate [Yb(PFO)₃] is found to be an efficient catalyst for the microwave-irradiated synthesis of dihydropyrano[3,2-b]chromenediones by the one-pot condensation of kojic acid, aldehydes, and 1,3-dicarbonyl compound under so

Full text of DOI:10.1002/jhet.2289

Month 2015
Synthesis and Bioassay of Dihydropyrano[3,2-b]chromenediones
Syama Sundar Chereddy, Bakthavatchala Reddy Nemallapudi, Satheesh Krishna Balam, Jaya Prakash Soora Harinath,
*
Radha Rani Chinthaparthi, and Suresh Reddy Cirandur
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, A.P., India
*
E-mail: csrsvu@gmail.com
Additional Supporting Information may be found in the online version of this article.
Received May 4, 2014
DOI 10.1002/jhet.2289
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Ytterbium perfluorooctanoate [Yb(PFO)3] is found to be an efficient catalyst for the microwave-irradiated
synthesis of dihydropyrano[3,2-b]chromenediones by the one-pot condensation of kojic acid, aldehydes, and
1,3-dicarbonyl compound under solvent-free conditions. This approach offers many advantages, such as
excellent product yields in short reaction time, solvent-free conditions, easy isolation of products, low catalyst
loading, reusability of the catalyst, and the absence of volatile and hazardous emissions. The preliminary
antimicrobial results of in vitro biological studies showed that most of the newly synthesized compounds
display a moderate inhibitory activity against bacteria and fungi. The complete characterization of synthesized
compounds and bioassay results are provided.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
kojic acid derivatives has become a great importance to
organic chemists. Some synthetic approaches have been
reported for them. Recently, Reddy et al. and Li et al.
reported the synthesis of 2-(hydroxymethyl)-7,7-dimethyl-
10-aryl-7,8-dihydropyrano[3,2-b]chromene-4,9(6H,10H)-diones
using InCl3, FeCl3–SiO2, and Alums as catalysts [14–16].
However, their methods are associated with one or more
disadvantages such as the use of an expensive, water-intolerant
and non-recyclable catalysts, and higher reaction temperatures.
Therefore, development of an efficient, inexpensive, and
eco-friendly synthesis for them is imperative. Ytterbium
perfluorooctanoate [Yb(PFO)3] has invoked an enormous
interest as a green and potential Lewis acid catalyst to con-
struct C–C, P–C, and C-heteroatom bonds in various reac-
tions [17–19]. It has received considerable attention because
of its low toxicity, cost effectiveness, air and water compati-
bility, ease of handling, recyclability, experimental simplicity,
and remarkable ability to suppress side reactions in acid-
sensitive substrates. Literature reveals that there are no reports
on the synthesis of dihydropyrano[3,2-b]chromenediones
under microwave-assisted solvent-free conditions mediated
by Yb(PFO)3. Our main objective is to develop a green
reaction methodology, which is faster, cleaner, and more
efficient than conventional reactions [20–22]. Herein, we report
a straight forward and efficient green method for synthesis of
kojic acid derivatives using Yb(PFO)3 as catalyst under micro-
wave irradiation in excellent yields. All the synthesized
compounds were evaluated for antimicrobial activity by disc-
diffusion method against Staphylococcus aureus, Klebsiella
pneumoniae, and fungi Aspergillus niger and Fusarium solani.
Green chemical synthetic approaches have many advan-
tages such as reduction in by-products, energy economy,
and toxic reaction waste [1]. However, solvent-free reac-
tions have attracted much interest and gained importance
for their experimental simplicity, less energy requirements,
and almost quantitative reactivity of the substrates due to
intimacy of the reagents [2]. Improving the substrates’
reactivity and product formation efficiency by energizing
the reactions with microwave irradiation is another aspect
in organic green chemical synthesis because of their spec-
tacular accelerations in reactions as a consequence of three
dimensional heating of the reaction mass that cannot be
achieved by classical heating [3]. Simple experimental
setup, high yields, improved selectivity, and clean reaction
pathways are additional features of microwave-assisted
preparation of organic compounds. Indeed, even reactions
that do not occur by conventional heating can be effec-
tively performed under microwave conditions. Combina-
tion of microwave irradiation and solvent-free procedures
offers an easier approach for organic synthetic transforma-
tions [4]. Recently, numerous important heterocycles have
been synthesized under solvent-free conditions accelerated
by microwave irradiation [5,6].
Kojic acid derivatives are important structural motifs for
many natural and synthetic compounds that possess high
bio-activity profiles such as antimelanogenic [7], tyrosinase
inhibitory activities [8], antimicrobial [9], anticonvulsant [10],
anti-inflammatory [11], whitening agent [12], antineoplastic
[13], and antiviral activities [10]. Consequently, synthesis of
© 2015 HeteroCorporation

S. S. Chereddy, B. R. Nemallapudi, S. K. Balam, J. P. Soora Harinath,
R. R. Chinthaparthi, and S. R. Cirandur
Vol 000
Table 1
RESULTS AND DISCUSSION
Effect of temperature on the synthesis of 4a.
Synthesis of dihydropyrano[3,2-b]chromenediones (4a–l)
has been accomplished by the reaction of cyclic 1,3-dicarbonyl
compound (1), aldehydes (2a–l), and kojic acid (3) in the
presence of Yb(PFO)3 as catalyst by microwave irradiation
under solvent-free condition at 80°C (Scheme 1).
Initially, the reaction was optimized at different temper-
atures ranging from 40 to 120°C under microwave irradia-
tion (Table 1) and found that at 80°C with 6 min of reaction
time, the highest product yield (94%) was achieved
(Table 1, Entry 3). The same reaction when carried out by
conventional heating at 80°C required longer time and
offered low yield (Table 1, Entry 6).
S. no.
Temperature (°C)
Time (min)
Yield (%)a
1
2
3
4
40
60
80
100
120
80
6
6
6
6
6
28
54
94
81
54
36
5
6b
120
aIsolated yield.
bReaction was carried out by conventional heating.
Table 2
Also, reaction was attempted without a catalyst as a con-
trol under the established conditions with higher tempera-
ture and prolonged reaction time and did not observe any
improvements; in fact, the reaction was sluggish, and the
product was isolated in very low yield (Table 2, Entry 10).
This shows that Yb(PFO)3 remarkably catalyzes this reaction
and is essential for them to occur. The yields were obviously
affected by the amount of Yb(PFO)3 loaded (Table 2, Entries
6–9). A 5 mol % of Yb(PFO)3 was sufficient, and excessive
amount of catalyst had no impact either on the rate of the
reaction or on the compound yield.
The catalytic activity of the recycled [Yb(PFO)3] was also
examined. The catalyst was recovered after each run, washed
three times with chloroform, dried, and tested for its activity
in subsequent runs. It was found that the catalyst could be
reused three times without the loss of activity (Table 2, Entry
8). To improve the yields further and to make the process green,
the reaction was run in different solvents and without a solvent
(Table 2). It was observed that in the presence of solvent, the
reaction takes longer time and gives lower yield of the product
under similar reaction conditions. This may be due to the com-
petitive adsorption of the solvent with the substrate molecule on
the catalyst surface. Hence, reaction under solvent-free condi-
tions affords high yields in less time, and this could be due to
a uniform distribution of the eutectic mixture of reactants being
in closer proximity to react than in solvent conditions. Thus, it
was established that 5 mol % of Yb(PFO)3 and 6min of micro-
wave irradiation under solvent-free conditions are the opti-
mized conditions for the effective completion of this reaction.
We extended the aforementioned reaction under opti-
mized conditions and prepared a library of dihydropyrano
[3,2-b]chromenediones (Table 3). The aromatic aldehydes
carrying both electron-withdrawing and electron-donating
Screening of solvents and catalyst loading for the synthesis of 4a by mi-
crowave irradiation.
Yb(PFO)3
(mol %)
Entry
Solvents
Time (min)
Yield (%)a
1
2
3
4
5
6
DCE
EtOH
CH3CN
THF
Toluene
Neat
Neat
Neat
Neat
Neat
10
10
10
10
10
10
7.5
5
30
30
30
30
30
6
6
6
6
120
45
64
63
37
34
93
94
7
8b
9
94, 94, 93
68
2.5
0
10
24
aIsolated yield.
bCatalyst was reused three times.
Table 3
Microwave-assisted synthesis of dihydropyrano [3,2-b]chromenediones
(4a–l).
Product
R
Time (min)
Yield (%)a
4a
4b
4c
4d
4e
4f
4g
4h
4i
C6H5
4-F C6H4
2-Cl C6H4
4-Cl C6H4
6
5
7
5
6
7
8
6
5
8
6
8
94
90
92
90
89
90
92
88
89
90
96
94
4-Me C6H4
4-OMe C6H4
3,4,5-OMe3 C6H2
2-OPh C6H4
3-NO2 C6H4
2-NO2 C6H4
3,5-Cl2 C6H3
3,5-OMe2 C6H3
4j
4k
4l
aIsolated yield.
Scheme 1. Yb(PFO)3 catalyzed neat synthesis of dihydropyrano [3,2-b]chromenediones.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Bioassay of Dihydropyrano[3,2-b]chromenediones
(5mol %) was taken in a reaction vessel and irradiated at 80°C for
a specified time (Table 3). The completion of the reaction was
confirmed by TLC. Methylene dichloride (10 mL) was added to
the mixture stirred and filtered to separate the catalyst that was
dried under vacuum and reused. The solvent from the filtrate was
evaporated, and the crude product was purified by column
chromatography on silica gel (Merck, 60–120 mesh, ethyl acetate–
hexane, 7:3) to afford pure substituted dihydropyrano[3,2-b]
chromenediones in 88–96% yield.
groups reacted successfully within 5–8 min and gave the
corresponding dihydropyrano[3,2-b]chromenediones in
88–96% yields. The structures of 4a–l were characterized
by 1H NMR, 13C NMR, IR, and mass spectral analysis.
A schematic mechanism for the catalytic activity of Yb
(PFO)3 in the synthesis of titled compounds (4a–l) should
be postulated as shown in Scheme 2. We supposed that the
reaction may proceed via heterodiene intermediate, which
was formed by standard Knovengal condensation of dimedone
to aldehyde catalyzed by Yb(PFO)3. Subsequent Diels
alder-type addition of kojic acid with heterodiene followed
by dehydration leads to desired product.
Spectral data for compounds
2-(Hydroxymethyl)-7,7-dimethyl-10-phenyl-7,8-dihydropyrano
[3,2-b]chromene-4,9(6H,10H)-dione (4a).
Solid, Yield: 94%,
Mp: 184–186°C; IR: 3361, 3078, 2920, 2892, 1660, 1635, 1440,
1375, 1220, 1194, 1076, 985, 948, 720 cmÀ1; 1H NMR (DMSO-d6):
δ 7.30–7.18 (m, 5H), 6.49 (s, 1H), 4.85 (s, 1H), 4.40–4.34 (m, 2H),
2.62–2.48 (m, 2H), 2.30–2.21 (m, 2H), 1.13 (s, 3H), 1.06 (s, 3H);
13C NMR (DMSO-d6): δ 196.8, 170.5, 168.4, 163.8, 150.8, 140.4,
136.6, 129.4, 128.5, 127.9, 112.8, 112.2, 60.4, 50.6, 39.8, 38.7,
32.4, 29.4, 27.5; ESI-MS (m/z): 353 [M + H]+. Anal. Calcd for
C21H20O5: C, 71.58; H, 5.72. Found: C, 71.52; H, 5.66.
CONCLUSION
We have developed a green and highly efficient methodol-
ogy for the synthesis of dihydropyrano[3,2-b]chromenediones
by the reaction of an aldehyde, kojic acid, and cyclic 1,3-
dicarbonyl compound in the presence of Yb(PFO)3 by
microwave irradiation under solvent-free conditions. The
advantages of this method are reduced reaction times, higher
yields, mild reaction condition, easy purification of the product,
and economic viability of the catalyst. Their antimicrobial activ-
ity as evaluated by the disc-diffusion method against S. aureus,
K. pneumoniae, and fungi A. niger and F. solani. All the com-
pounds exhibited moderate to good antimicrobial activity.
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-florophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4b). Solid,
Yield: 90%, Mp: 162–164°C; IR: 3362, 2950, 2932, 2854, 1678,
1637, 1604, 1510, 1440, 1378, 1220, 1191, 1158, 1078, 964, 848,
1
682 cmÀ1; H NMR (DMSO-d6): δ 7.26–7.21 (m, 2H), 6.98–6.92
(m, 2H), 6.54 (s, 1H), 4.89 (s, 1H), 4.42–4.30 (m, 2H), 2.62–2.54
(m, 2H), 2.28–2.17 (m, 2H), 1.12 (s, 3H), 1.05 (s, 3H); 13C NMR
(DMSO-d6): δ 195.9, 170.2, 168.4, 165.8, 161.7, 150.4, 138.1,
136.4, 129.8, 129.4, 115.6, 114.2, 112.4, 112.0, 61.8, 50.8, 40.4,
38.8, 32.4, 28.8, 27.9; ESI-MS (m/z): 371 [M + H]+. Anal. Calcd
for C21H19FO5: C, 68.10; H, 5.17. Found: C, 68.04; H, 5.14.
2-(Hydroxymethyl)-7,7-dimethyl-10-(2-chlorophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4c). Solid,
Yield: 92%, Mp: 216–218°C; IR: 3290, 2952, 2930, 2862, 1674,
EXPERIMENTAL
All chemicals purchased from Sigma-Aldrich were used with-
out further purification. The Yb(PFO)3 was prepared according to
the literature procedure [23]. IR spectra were recorded on FT-IR
spectrometer. 1H and 13C NMR spectra were recorded in DMSO-d6
using 300 MHz NMR spectrometer. The chemical shifts (δ) were
reported with respect to TMS as an internal standard. The coupling
constants (J) are quoted in hertz (Hz). Mass spectra were recorded
on a GEOL GC MATE spectrometer by electrospray ionization
(ESI) technique.
1
1635, 1598, 1468, 1448, 1379, 1220, 1115, 1080, 752 cmÀ1; H
NMR (DMSO-d6): δ 7.36–7.30 (m, 1H), 7.24–7.18 (m, 3H), 6.48
(s, 1H), 5.42 (s, 1H), 4.42–4.34 (m, 2H), 2.68–2.65 (m, 2H),
2.28–2.21 (m, 2H), 1.10 (s, 3H), 1.04 (s, 3H); 13C NMR
(DMSO-d6): δ 196.4, 170.2, 168.4, 165.2, 150.5, 136.8, 137.2,
133.8, 130.5, 129.4, 126.7, 112.4, 111.2, 59.8, 49.2, 40.5, 35.4,
31.2, 29.8, 27.2; ESI-MS (m/z): 371 [M + H]+. Anal. Calcd for
C21H19ClO5: C, 65.20; H, 4.95. Found: C, 65.14; H, 4.88.
General procedure for the synthesis of dihydropyrano[3,2-b]
chromenediones. A mixture of aldehyde (1mmol), kojic acid
(1mmol), 1,3-dicarbonyl compound (1.1 mmol), and Yb(PFO)3
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-chlorophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4d). Solid,
Yield: 90%, Mp: 204–206°C; IR: 3326, 2960, 2932, 2874, 1674,
Scheme 2. A plausible reaction pathway catalyzed by Yb(PFO)3.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

S. S. Chereddy, B. R. Nemallapudi, S. K. Balam, J. P. Soora Harinath,
R. R. Chinthaparthi, and S. R. Cirandur
Vol 000
1645, 1610, 1492, 1448, 1378, 1214, 1195, 1074, 1015, 958,
850 cmÀ1 1H NMR (DMSO-d6): δ 7.24–7.16 (m, 4H), 6.50
[M+ H]+. Anal. Calcd for C22H22O6: C, 69.10; H, 5.80. Found:
C, 69.04; H, 5.74.
;
(s, 1H), 4.88 (s, 1H), 4.40–4.36 (m, 2H), 2.64–2.58 (m, 2H),
2.32–2.22 (m, 2H), 1.12 (s, 3H), 1.04 (s, 3H); 13C NMR (DMSO-d6):
δ 196.4, 170.8, 168.4, 164.5, 150.2, 138.8, 138.0, 132.9, 129.5, 129.4,
112.8, 111.4, 60.5, 50.4, 40.7, 38.0, 32.4, 28.5, 27.1; ESI-MS (m/z):
387 [M + H]+. Anal. Calcd for C21H19ClO5: C, 65.20; H, 4.95.
Found: C, 65.14; H, 4.87.
2-(Hydroxymethyl)-7,7-dimethyl-10-(3,4,5-trimethoxy-phenyl)-
7,8-dihydropyrano[3,2-b]chromene- 4,9(6H,10H)-dione (4g).
Solid, Yield: 92%, Mp: 174–176°C; IR: 3292, 2964, 2926,
2864, 1672, 1636, 1594, 1504, 1420, 1376, 1330, 1218,
1128, 1075, 960 cmÀ1 1H NMR (DMSO-d6): δ 6.85–6.54
;
(m, 3H), 6.39 (s, 1H), 4.84 (s, 1H), 4.42–4.36 (m, 2H), 3.82
(s, 6H), 3.80 (s, 3H), 2.69–2.60 (m, 2H), 2.32–2.24 (m, 2H),
1.15 (s, 3H), 1.04 (s, 3H); 13C NMR (DMSO-d6): δ 196.4,
170.8, 168.0, 164.4, 152.9, 150.9, 138.0, 136.4, 112.8,
106.7, 60.4, 60.2, 55.9, 50.4, 40.8, 38.7, 32.7, 29.6, 27.4;
ESI-MS (m/z): 443 [M + H]+. Anal. Calcd for C24H26O8: C,
65.15; H, 5.92. Found: C, 65.07; H, 5.85.
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-methylphenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4e). Solid,
Yield: 89%, Mp: 214–216°C; IR: 3364, 2964, 2932, 2848, 1658,
1632, 1444, 1372, 1218, 1180, 1118, 1072, 952, 864, 625cmÀ1
;
1H NMR (DMSO-d6): δ 7.25–7.10 (m, 2H), 7.01–6.94 (m, 2H),
6.48 (s, 1H), 4.82 (s, 1H), 4.40–4.32 (m, 2H), 2.68–2.59 (m, 2H),
2.32 (s, 3H), 2.24–2.18 (m, 2H), 1.10 (s, 3H), 1.03 (s, 3H); 13C
NMR (DMSO-d6): δ 196.1, 172.4, 168.8, 162.8, 152.4, 138.5,
137.7, 137.0, 129.4, 127.8, 112.5, 111.1, 60.2, 50.1, 40.5, 37.7,
32.3, 29.7, 27.1, 21.2; ESI-MS (m/z): 367 [M+ H]+. Anal. Calcd
for C22H22O5: C, 72.12; H, 6.05. Found: C, 72.04; H, 6.00.
2-(Hydroxymethyl)-7,7-dimethyl-10-(4-methoxy-phenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4f). Solid,
Yield: 90%, Mp: 180–182°C; IR: 3352, 2956, 2926, 2835, 1670,
1638, 1512, 1444, 1378, 1220, 1198, 1118, 1028, 948, 862,
636 cmÀ1; 1H NMR (DMSO-d6): δ 7.20–7.12 (m, 2H), 7.04–6.94
(m, 2H), 6.42 (s, 1H), 4.86 (s, 1H), 4.38–4.24 (m, 2H), 3.76
(s, 3H), 2.62–2.52 (m, 2H), 2.38–2.30 (m, 2H), 1.14 (s, 3H),
1.05 (s, 3H); 13C NMR (DMSO-d6): δ 196.5, 172.0, 168.5,
162.8, 160.0, 152.7, 136.9, 132.8, 130.0, 115.2, 112.4, 130.2,
60.4, 55.4, 51.0, 41.2, 36.5, 32.4, 29.8, 27.5; ESI-MS (m/z): 383
2-(Hydroxymethyl)-7,7-dimethyl-10-(2-phenoxy-phenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4h). Solid,
Yield: 88%, Mp: 192–194°C; IR: 3296, 2960, 2923, 2869, 1673,
1637, 1598, 1508, 1422, 1375, 1329, 1220, 1126, 1076,
1
956 cmÀ1; H NMR (DMSO-d6): δ 7.49–7.32 (m, 5H), 7.04–6.96
(m, 4H), 6.52 (s, 1H), 4.84 (s, 1H), 4.42–4.30 (m, 2H), 2.66–2.59
(m, 2H), 2.42–2.35 (m, 2H), 1.14 (s, 3H), 1.09 (s, 3H); 13C NMR
(DMSO-d6): δ 196.4, 171.5, 168.8, 164.2, 152.4, 150.8, 148.4
136.4, 135.2, 128.8, 122.7, 121.8, 113.8, 106.8, 60.4, 50.4, 40.8,
37.8, 32.8, 29.5, 27.2; ESI-MS (m/z): 445 [M + H]+. Anal. Calcd
for C27H24O6: C, 72.96; H, 5.44. Found: C, 72.88; H, 5.40.
2-(Hydroxymethyl)-7,7-dimethyl-10-(3-nitrophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4i). Solid,
Yield: 89%, Mp: 212–214°C; IR: 3392, 2960, 2926, 2850, 1666,
1632, 1600, 1532, 1446, 1370, 1352, 1210, 1144, 1084,
Table 4
Antibacterial activity of 4a–l.
Zone of inhibition (mm)
Compound
Concentration (μM/disc)
Staphylococcus aureus
Klebsiella pneumoniae
4a
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
28
33
30
33
29
32
30
32
26
32
26
33
27
33
27
32
25
28
26
31
29
35
28
32
35
41
31
37
32
36
32
34
32
35
29
36
28
35
29
35
38
34
28
32
29
34
31
37
29
34
37
42
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
Chloramphenicol
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2015
Synthesis and Bioassay of Dihydropyrano[3,2-b]chromenediones
1
674 cmÀ1; H NMR (DMSO-d6): δ 8.18–8.01 (m, 2H), 7.64–7.51
(m, 1H), 6.48 (s, 1H), 4.84 (s, 1H), 4.45–4.32 (m, 2H), 2.78–2.66
(m, 2H), 2.32–2.24 (m, 2H), 1.14 (s, 3H), 1.06 (s, 3H); 13C NMR
(DMSO-d6): δ 196.8, 171.4, 168.7, 164.5, 150.6, 147.9, 143.0,
138.2, 134.5, 130.8, 124.7, 122.8, 112.8, 112.0, 60.5, 50.2, 40.5,
38.4, 32.8, 28.9, 27.5; ESI-MS (m/z): 398 [M + H]+. Anal. Calcd
for C21H19NO7: C, 63.47; H, 4.82; N, 3.52. Found: C, 63.38; H,
4.78; N, 3.48.
124.9, 111.4, 113.6, 59.6, 50.2, 45.6, 37.3, 32.3, 28.8, 27.2;
ESI-MS (m/z): 422 [M + H]+. Anal. Calcd for C21H18Cl2O5: C,
59.87; H, 4.31. Found: C, 59.82; H, 4.28.
10-(3,5-Dimethoxyphenyl)-2-(hydroxymethyl)-7,7-dimethyl-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4l). Solid,
Yield: 94%, Mp: 182–184°C; IR: 3352, 2962, 2926, 1636, 1523,
1376, 1221, 1191, 1073, 955, 844 cmÀ1; 1H NMR (DMSO-d6): δ
7.17–7.10 (m, 2H), 6.82–6.75 (m, 1H), 6.31 (s, 1H), 4.74 (s, 1H),
4.28–4.12 (m, 2H), 3.75 (s, 6H), 2.65–2.49 (m, 2H), 2.27–2.10
(m, 2H), 1.12 (s, 3H), 1.06 (s, 3H); 13C NMR (DMSO-d6): δ
195.4, 169.6, 168.3, 163.6, 154.7, 150.5, 137.1, 136.5, 132.6,
129.8, 129.7, 124.0, 111.4, 111.1, 59.0, 54.6, 53.2, 49.6, 44.6,
37.0, 31.8, 28.1, 26.8; ESI-MS (m/z): 413 [M+ H]+. Anal. Calcd
for C23H24O7: C, 66.98; H, 5.87; Found: C, 66.94; H, 5.82.
2-(Hydroxymethyl)-7,7-dimethyl-10-(2-nitrophenyl)-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4j). Solid,
Yield: 90%, Mp: 190–192°C; IR: 3368, 2964, 2928, 1638, 1525,
1385, 1221, 1195, 1072, 955, 834 cmÀ1 1H NMR (DMSO-
;
d6): δ 7.27–7.22 (m, 2H), 7.02–6.96 (m, 2H), 6.35 (s, 1H),
5.48–5.40 (br s, 1H), 4.83 (s, 1H), 4.29–4.14 (m, 2H), 2.70–2.57
(m, 2H), 2.28–2.14 (m, 2H), 1.13 (s, 3H), 1.06 (s, 3H); 13C NMR
(DMSO-d6): δ 194.9, 170.0, 168.8, 164.4, 149.9, 138.2, 137.0,
132.9, 130.7, 129.5, 128.9, 127.5, 111.9, 110.0, 58.9, 49.8, 45.0,
34.8, 31.8, 28.4, 27.0; ESI-MS (m/z): 398 [M + H]+. Anal. Calcd
for C21H19NO7: C, 63.47; H, 4.82; N, 3.52. Found: C, 63.38; H,
4.78; N, 3.48.
ANTIMICROBIAL ACTIVITY
The compounds (4a–l) were tested for in vitro antimicro-
bial activity against the Gram-positive bacteria S. aureus,
the Gram-negative bacteria K. pneumoniae, and fungi A,
niger and F. solani. The preliminary screening was carried
out by agar disc-diffusion method [24]. Chloramphenicol
and ketoconazole were used as control drugs. The biologi-
cal assay was performed as shown later. Briefly, sterile filter
paper discs (6 mm diameter) moistened with the test com-
pound solution in DMSO of specific concentrations of
100 and 200 μM/disc were carefully placed on the agar culture
plates that had been previously inoculated separately with
the microorganisms. The plates were incubated at 37°C,
and the diameter of the growth inhibition zones was mea-
sured after 24 h in case of bacteria and after 48 h in case of
fungi. The observed data on the antimicrobial activity of
the compounds and control drugs are given in Tables 4
and 5. The preliminary results revealed that most of these
compounds showed reasonable activity against both bacte-
ria and fungi.
10-(3,5-Dichlorophenyl)-2-(hydroxymethyl)-7,7-dimethyl-7,8-
dihydropyrano[3,2-b]chromene-4,9(6H,10H)-dione (4k). Solid,
Yield: 96%, Mp: 158–160°C; IR: 3362, 2960, 2927, 1639, 1508,
1358, 1220, 1190, 1078, 956, 854 cmÀ1; H NMR (DMSO-d6): δ
1
7.37–7.32 (m, 1H), 7.24–7.16 (m, 2H), 6.39 (s, 1H), 5.35 (s, 1H),
4.30–4.14 (m, 2H), 2.72–2.59 (m, 2H), 2.27–2.13 (m, 2H), 1.14
(s, 3H), 1.10 (s, 3H); 13C NMR (DMSO-d6): δ 195.5, 170.2,
168.8, 163.9, 158.9, 151.7, 136.9, 133.5, 131.5, 129.4, 128.2,
Table 5
Antifungal activity of 4a–l.
Zone of inhibition (mm)
Concentration
(μM/disc)
Aspergillus
niger
Fusarium
solani
Compound
4a
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
100
200
30
32
28
31
31
33
29
32
31
32
27
29
28
31
26
29
31
32
28
30
30
31
29
32
36
39
32
35
30
31
28
29
26
28
32
33
28
29
29
30
28
30
32
34
29
31
31
33
32
34
38
42
4b
4c
Acknowledgments. The authors express their grateful thanks to
Prof. C.D. Reddy, Department of Chemistry, Sri Venkateswara
University, Tirupati, for his helpful discussions, and also, we
thank the Council of Scientific and Industrial Research (CSIR),
New Delhi, for providing financial assistance (S. No.: 02(0137)/
13/EMR-II, dated 12-04-2013).
4d
4e
4f
4g
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4h
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