Microwave-assisted, solvent-free, one-pot, three-component synthesis of fused pyran derivatives containing benzothiazole nucleus catalyzed by pyrrolidine-acetic acid and their biological evaluation

Article abstract of DOI:10.1007/s00706-016-1875-7

Abstract: An efficient method for the synthesis of fused pyran derivatives has been developed by a one-pot, three-component, solvent-free reaction of 1H-pyrazole-4-carbaldehyde and various active methylenes and malononitriles under microwave irradiation in the presence of pyrrolidine-acetic acid as bifunctional catalyst. The salient features of this protocol are the solvent-free reaction, shorter reaction time, greater selectivity, and straightforward workup procedure. All the synthesized compounds were confirmed by analytical and spectral data. The synthesized compounds were investigated against a representative panel of pathogenic strains using the broth microdilution MIC method for their in vitro antimicrobial activity. Graphical abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s00706-016-1875-7

Monatsh Chem
DOI 10.1007/s00706-016-1875-7
ORIGINAL PAPER
Microwave-assisted, solvent-free, one-pot, three-component
synthesis of fused pyran derivatives containing benzothiazole
nucleus catalyzed by pyrrolidine-acetic acid and their biological
evaluation
Haresh B. Patel1 Jayvirsinh D. Gohil1 Manish P. Patel1
•
•
Received: 5 April 2016 / Accepted: 13 November 2016
Ó Springer-Verlag Wien 2017
Introduction
Abstract An efficient method for the synthesis of fused
pyran derivatives has been developed by a one-pot, three-
component, solvent-free reaction of 1H-pyrazole-4-carb-
aldehyde and various active methylenes and malononitriles
under microwave irradiation in the presence of pyrrolidine-
acetic acid as bifunctional catalyst. The salient features of
this protocol are the solvent-free reaction, shorter reaction
time, greater selectivity, and straightforward workup pro-
cedure. All the synthesized compounds were confirmed by
analytical and spectral data. The synthesized compounds
were investigated against a representative panel of patho-
genic strains using the broth microdilution MIC method for
their in vitro antimicrobial activity.
Fused pyran derivatives represent an important class of
compounds, which possess a broad spectrum of biological
activities such as anticancer, antiviral, antimicrobial, anti-
malarial, anti-HIV, antituberculosis, antiinflammatory, and
antifungal [1–10]. Other biologically active moiety
chromenes were found in plants [11], and the synthesis of
new pharmacophores for medicinal chemistry has been
used as a valuable lead for the design and development of
drugs. Benzothiazole is also a bioactive nucleus that covers
a large domain of pharmacological activities serving as
anti-microbial, antitumor, anti-inflammatory, and analgesic
agents [12–14].
Graphical abstract
Multicomponent reactions (MCRs) have been developed
as an efficient, environmentally friendly, and economic
protocol in the current decade for a range of pharmaco-
logically important compounds. These multicomponent
reactions have become an important tool for atomic
economy, simple purification of products, and rapid gen-
eration of molecular complexity, diversity with predefined
functionality in chemical biology, and drug discovery
[15–17]. Small organic molecules such as amino acids have
shown promising and highly efficient catalytic activities for
multicomponent reactions. However, among all the various
organocatalysts, the pyrrolidine-acetic acid catalyst is one
of the most versatile for many important organic reactions
and asymmetric transformations such as Michael, Mannich,
Aldol, and Diels-Alder reactions [18–21].
Keywords Microwave Á Solvent free Á Fused pyran Á
Benzothiazole Á Pyrrolidine-acetic acid
Electronic supplementary material The online version of this
article (doi:10.1007/s00706-016-1875-7) contains supplementary
material, which is available to authorized users.
Previously, fused pyran derivatives were prepared by
using different synthetic approaches [22–29]. However,
some limitations were observed in these methods such as
longer reaction times, difficulties in the workup, and poor
yield with various solvents. In the present study, we have
used some acid as well as base catalysts such as
& Manish P. Patel
patelmanish1069@yahoo.com
1
Department of Chemistry, Sardar Patel University,
Vallabh Vidyanagar, Gujarat 388120, India
123

H. B. Patel et al.
CH3COOH, p-TsOH, piperidine, K2CO3, and NaOH; they
did not lead to formation of the desired product. Also, L-
proline was a weak catalyst for this reaction; however,
these catalysts have some drawbacks such as side products,
low yields, and lesser selectivity. We thus developed an
alternative solvent-free, microwave-assisted organic syn-
thesis (MAOS) approach using pyrrolidine-acetic acid as
an efficient catalyst, which facilitates designing the title
derivatives and avoids the use of volatile organic solvents.
In continuation of our previous investigations on
biopotent heterocycles [30–34], our efforts are focused to
design and synthesize biologically potent heterocyclic
systems via a one-pot, three-component, solvent-free
reaction triggered by 10 mol% pyrrolidine-acetic acid
(Scheme 1) under microwave assistance assuming the
assimilation of more than one biopotent nucleus in a single
scaffold.
Results and discussion
Analytical results
Compounds 1-(substituted benzo[d]thiazol-2-yl)-3-(substi-
tuted phenyl)-1H-pyrazole-4-carbaldehyde 5a–5d were
prepared by Vilsmeier-Haack reaction, according to the
literature procedure [35, 36]. Reaction of 1-(benzo[d]thia-
zol-2-yl)-3-(4-methylphenyl)-1H-pyrazole-4-carbaldehyde
(5b) (10 mmol), compound 6e (10 mmol), malononitrile
(10 mmol), and a catalytic amount of pyrrolidine-acetic
acid (10 mol%) afforded compound 7j (Table 1). Initially,
the reaction was investigated using different catalysts, such
as piperidine, K2CO3, and NaOH, which were tried as base
catalysts for the model reaction. They did not lead to for-
mation of the desired product 7a–7t but formed compound
8. Only pyrrolidine-acetic acid catalyst surprisingly led to
Scheme 1
123

Microwave-assisted solvent-free one-pot three-component synthesis of fused pyran derivatives…
the reaction pathway being directed toward the formation
of compounds 7a–7t.
afforded 74 and 80% of the product even after irradiation
for 7 min. An additional increase of the catalyst loading to
20% (entry 4) did not improve the yield (68%). On the
contrary, the reaction slowed down on adding more than
20 mol% of the catalyst. These pyrrolidine-acetic acid
catalysts were also screened in the same way but using a
series of different solvents. When the reaction was per-
formed in acetonitrile (entry 5), n-butanol (entry 7), DMF
(entry 9) and THF (entry 10) were obtained in lower yields
of products 7a–7t, whereas in water (entry 8) we failed to
obtain products 7a–7t. The best results were obtained in
methanol (entry 6) and ethanol (entry 11). Surprisingly,
however, when the reaction was carried out under solvent-
free conditions, both the yield and reaction time were
significantly improved. In this study pyrrolidine-acetic acid
emerged as a model catalyst under solvent-free conditions
and was employed for the synthesis of all other targeted
compounds 7a–7t.
Different catalysts were attempted, and the result is
shown in Table 1. CH3COOH and p-TsOH were also used
to try to obtain the desired product 7j. The reaction did not
occur even after a long reaction time of up to 10 min
(entries 1 and 2). It was also investigated by employing a
variety of bases including piperidine (entry 3), K2CO3
(entry 4), and NaOH (entry 5), which resulted the Kno-
evenagel adduct in all cases. In case of the catalyst-free
(entry 6) condition, the reaction failed to occur. In addition,
we performed the reaction with a bi-functional catalyst
such as L-proline and pyrrolidine-acetic acid catalyst; L-
proline was found to push the reaction efficiently in the
proper direction, but it was a poor catalyst of this reaction,
and we obtained a lower yield (up to 37%) (entry 7). Using
pyrrolidine-acetic acid, we obtained the best result (up to
86%) under solvent-free conditions (entry 8).
Furthermore, we checked the effects of varying amounts
of catalyst loading without and with different solvents
(Table 2). It was very surprising to observe that the reac-
tion pathway was directed toward the formation of
compounds 7a–7t. The reaction was performed using 5, 10,
15 and 20 mol% of the catalyst and was monitored for
5–7 min. It was observed that 10 mol% (entry 2) of the
catalyst loading provided the maximum yield (86%) in
5 min, while 5 and 15 mol% (entries 1, 3) of the catalyst
The structures of all the newly synthesized compounds
1
were characterized by H NMR, 13C NMR, FT-IR, ele-
mental analysis, and mass spectrometry. The IR spectrum
of compounds exhibited characteristic absorption bands
3450 and 3290 (asym. and sym. str. of NH2), 2200 (C:N
str.), and 1682 (C=O str.) cm-1. The 1H NMR spectrum of
compound 7j indicated the presence of one singlet peak at
the d = 4.66 ppm of –CH (H5) proton and the disappear-
ance of a singlet from 10.12 ppm of –CHO, which clearly
Table 1 Effect of different catalysts on the model reaction under microwave irradiation
Entry
Catalyst (10 mol%)
Solvent
Time/min
Yield/%
a
1
2
3
4
5
6
7
8
CH3COOH
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
–
10
10
6
–
a
p-TsOH
–
Piperidine
76b
65b
79b
K2CO3
7
NaOH
5
a
–
7
–
L-Proline
7
37c
86c
Pyrrolidine-acetic acid (1:1)
5
Reaction conditions: 1H-pyrazole-4-carbaldehyde 5b (10 mmol), compound 6e (10 mmol), malononitrile (10 mmol), and different catalysts
(10 mol%) under microwave irradiation, time 5–10 min
a
Reaction failed to occur
b
Isolated yield of compound 8
c
Isolated yield of compound 7j
123

H. B. Patel et al.
Yielda/%
Table 2 Screening of catalysts and solvents in the model reaction under microwave irradiation
Entry
Catalyst (mol%)
Solvent
1
Pyrrolidine-acetic acid (5)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (15)
Pyrrolidine-acetic acid (20)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (10)
Pyrrolidine-acetic acid (10)
–
74
86
80
68
49
72
52
–
2
–
3
–
4
–
5
Acetonitrile
Methanol
n-Butanol
Water
DMF
6
7
8
9
52
56
78
10
11
THF
Ethanol
Reaction conditions: 1H-pyrazole-4-carbaldehyde 5b (10 mmol), compound 6e (10 mmol), malononitrile (10 mmol), and pyrrolidine-acetic acid
as catalysts in various solvents under microwave irradiation, time 5–7 min
a
Isolated yield of compound 7j
Table 3 Substituent pattern and reaction condition for the synthesized compounds 7a–7t
Entrya
Prod.
R1
R2
Het.
Time/min
Yieldb/%
1
7a
7b
7c
7d
7e
7f
H
F
Dimedone
7
5
5
5
7
6
5
7
7
5
6
5
5
7
6
6
6
7
7
5
71
78
73
68
75
83
72
83
73
86
78
75
81
75
70
79
70
84
76
82
2
H
F
4-Hydroxy-6-methylpyran-2-one
4-Hydroxycoumarin
3
H
F
4
H
F
3-Methyl-5-hydroxypyrazole
2-Hydroxy-1,4-naphthoquinone
Dimedone
5
H
F
6
H
Me
Me
Me
Me
Me
F
7
7g
7h
7i
H
4-Hydroxy-6-methylpyran-2-one
4-Hydroxycoumarin
8
H
9
H
3-Methyl-5-hydroxypyrazole
2-Hydroxy-1,4-naphthoquinone
Dimedone
10
11
12
13
14
15
16
17
18
19
20
a
7j
H
7k
7l
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
F
4-Hydroxy-6-methylpyran-2-one
4-Hydroxycoumarin
7m
7n
7o
7p
7q
7r
7s
F
F
3-Methyl-5-hydroxypyrazole
2-Hydroxy-1,4-naphthoquinone
Dimedone
F
Me
Me
Me
Me
Me
4-Hydroxy-6-methylpyran-2-one
4-Hydroxycoumarin
3-Methyl-5-hydroxypyrazole
2-Hydroxy-1,4-naphthoquinone
7t
Reaction conditions: 1H-pyrazole-4-carbaldehyde 5a–5d (10 mmol), compound 6a–6e (10 mmol), malononitrile (10 mmol), and pyrrolidine-
acetic acid as catalyst (10 mol%) under microwave irradiation, time 5–7 min
b
Isolated yield of compound 7a–7t
confirmed the cyclization of the Knoevenagel intermediate.
The singlet at 7.31–7.12 ppm exhibits (Ar–H?NH2) pro-
tons of the pyran ring (Table 3).
formation of the heterylidenenitrile, containing the elec-
tron-poor C=C double bond from the Knoevenagel
condensation between pyrazolyl aldehydes 5b and
malononitrile by loss of water molecules. Finally, Michael
addition of compound 6e to the formed unsaturated nitrile
yielded an intermediate. The enolate O-atom of the formed
The mechanistic pathway for the development of fused
pyran derivative 7j catalyzed by pyrrolidine-acetic acid is
outlined in Scheme 2. The reaction proceeded via in situ
123

Microwave-assisted solvent-free one-pot three-component synthesis of fused pyran derivatives…
Scheme 2
intermediate attacked the nitrile group and a subsequent
cm3). Compounds 7c, 7e, 7f, 7k, 7m, and 7t
H-atom shift led to the final compound 7j.
(MIC = 100 lg/cm3) elicited excellent activity as com-
pared to ampicillin (MIC = 250 lg/cm3) and had similar
potency as compared to ciprofloxacin (MIC = 100 lg/
cm3) against C. tetani. Compound 7g (MIC = 100 lg/cm3)
was found equipotent, whereas compound 7m
(MIC = 62.5 lg/cm3) showed excellent activity compared
to ampicillin (MIC = 100 lg/cm3) against S. aureus.
Against the gram-negative bacteria E. coli, compound
7n (MIC = 62.5 lg/cm3) showed the highest activity,
whereas compounds 7c and 7d (MIC = 100 lg/cm3)
Antimicrobial activity
Investigation of the antimicrobial activity data (Table 4)
revealed that some compounds showed good to excellent
antibacterial and antifungal activity against the represen-
tative species when compared with the standard drugs such
as ampicillin, ciprofloxacin, norfloxacin, nystatin, and
griseofulvin.
Against the gram-positive bacteria B. subtilis, com-
pounds 7b, 7m, and 7t (MIC = 100 lg/cm3) were found to
be equipotent as compared to ampicillin (MIC = 100 lg/
showed
comparable
activity
to
ampicillin
(MIC = 100 lg/cm3). Against S. typhi, compounds 7h,
7n, 7o, and 7q (MIC = 100 lg/cm3) were found
123

H. B. Patel et al.
Table 4 In vitro antimicrobial activity of 7a–7t MICs (lg/cm3)
Sr. no.
Comp.
Gram-positive bacteria
Gram-negative bacteria
Fungi
CA
BS
MTCC 441
CT
MTCC 449
SA
MTCC 96
EC
MTCC 443
ST
MTCC 98
VC
MTCC 3906
TR
MTCC 296
MTCC 227
1
7a
7b
7c
7d
7e
7f
250
100
250
250
200
250
200
200
500
500
250
250
100
250
125
500
250
500
250
100
100
50
250
250
100
500
100
100
500
250
250
500
100
250
100
250
500
500
250
200
250
100
250
50
500
500
500
250
500
250
100
500
250
200
125
250
62.5
250
500
500
250
200
500
500
100
50
200
250
100
100
200
500
250
125
250
200
200
200
200
62.5
125
200
125
100
250
200
100
50
200
500
200
125
250
500
250
100
250
200
250
250
125
100
100
250
100
200
500
250
100
50
250
250
100
250
200
250
200
250
500
500
200
250
125
250
100
500
125
100
250
100
250
50
[1000
1000
500
1000
500
1000
1000
250
1000
500
1000
1000
250
250
250
1000
500
1000
1000
250
–
[1000
500
2
3
1000
250
4
5
1000
[1000
1000
1000
1000
500
6
7
7g
7h
7i
8
9
10
7j
11
7k
7l
500
12
[1000
100
13
7m
7n
7o
7p
7q
7r
7s
14
500
15
500
16
1000
1000
[1000
[1000
500
17
18
19
20
7t
Ampicillin
–
Chloramphenicol
Ciprofloxacin
Norfloxacin
Nystatin
–
–
50
100
50
25
25
25
50
–
–
10
10
10
10
100
–
–
–
–
–
–
–
–
100
500
100
Griseofulvin
–
–
–
–
–
–
100
Bold numbers indicate more or equivalent potent compounds compared to standard drugs
BS, Bacillus subtilis; CT, Clostridium tetani; SA, Staphylococcus aureus; EC, Escherichia coli; ST, Salmonella typhi; VC, Vibrio cholerae; CA,
Candida albicans; TR, Trichophyton rubrum. MTCC, microbial type culture collection
equipotent to ampicillin (MIC = 100 lg/cm3). Com-
Conclusion
pounds 7c, 7o, 7r, 7t (MIC = 100 lg/cm3), 7m, 7q
(MIC = 125 lg/cm3), and 7e, 7g, 7k (MIC = 200 lg/
In summary, we have introduced a highly efficient
cm3) were more potent compared to ampicillin
microwave-assisted, one-pot, three-component protocol
(MIC = 250 lg/cm3), and compounds 7c, 7o, 7r, and 7t
for the synthesis of fused pyran derivatives in the
demonstrated equipotent activity to norfloxacin
(MIC = 100 lg/cm3) against V. Cholerae.
presence of pyrrolidine-acetic acid under solvent-free
conditions. This protocol makes use of simple and
readily available precursors such as 1-(substituted
benzo[d]thiazol-2-yl)-3-(substituted phenyl)-1H-pyra-
zole-4-carbaldehyde 5a–5d, compounds 6a–6e, and
malononitrile. The present study expands the scope of
the area dealing with fused pyran derivatives bearing
benzothiazole nuclei, considering their potent antimi-
crobial activities. Some magnificent results have been
obtained with the fused pyran scaffold. Compounds 7c,
7e, 7h, 7m, 7n, 7o, 7q, 7r, and 7t were found to be the
most efficient antimicrobials in the series. It is worth
For exploration of anti-fungal screening (Table 4),
against C. albicans, compounds 7h, 7m, 7n, 7o, and 7t
(MIC = 250 lg/cm3) showed excellent activity, and
compounds 7c, 7e, 7j, and 7q (MIC = 500 lg/cm3) were
equally active compared to griseofulvin (MIC = 500 lg/
cm3). Against T. rubrum, compound 7m (MIC = 100 lg/
cm3) was found equipotent compared to nystatin and
griseofulvin (MIC = 100 lg/cm3); the remaining com-
pounds showed poor antifungal activity compared to
nystatin and griseofulvin.
123

Microwave-assisted solvent-free one-pot three-component synthesis of fused pyran derivatives…
and dried. Products 7a–7t were achieved quantitatively (up
to 86% yield) with excellent purity.
mentioning that fused pyran derivatives bearing a
benzothiazole nucleus have become a vital area of
antimicrobial medicine research.
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(4-fluorophenyl)-
1H-pyrazol-4-yl]-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (7a, C28H22FN5O2S)
Experimental
Yellow powder; yield 71%; m.p.: 226 °C; IR (KBr):
All reactions were performed with commercially avail-
able reagents and were used without further purification.
All reactions were monitored by thin-layer chromatogra-
phy (TLC, on aluminum plates coated with silica gel
60F254, 0.25 mm thickness, Merck) carried out on fluo-
rescent-coated plates, and detection of the components
was made by exposure to iodine vapors or UV light.
Melting points of all the title compounds were determined
by the open tube capillary method (using silicon oil 350
cst). The microwave-assisted reactions were conducted in
a ‘‘RAGA’s Modified Electromagnetic Microwave Sys-
tem’’ whereby microwaves are generated by a magnetron
at a frequency of 2450 MHz, having adjustable output
power levels, i.e., ten levels from 140 to 700 W, and with
an individual sensor for temperature control (fiber optic is
used as an individual sensor for temperature control) with
attachment of the reflux condenser with constant stirring
(thus avoiding the risk of high pressure development).
The IR spectra were recorded on a PerkinElmer Spectrum
GX FT-IR Spectrophotometer (PerkinElmer, USA) using
ꢀ
m = 3445, 3312 (asym., sym. str. of NH2), 2197 (C:N
1
str.), 1694 (C=O str.), 1228 (Ar–C–F str.) cm-1; H NMR
(400 MHz, DMSO-d6): d = 1.06 (s, 3H, CH3), 1.13 (s, 3H,
CH3), 2.20–2.48 (4H, m, 2 9 CH2), 4.47 (s, 1H, H4), 7.02
(s, 2H, NH2), 7.32–8.10 (m, 8H, Ar–H), 8.51 (s, 1H,
pyrazole H5) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 25.9, 28.0, 28.7, 32.1, 50.5, 58.3, 112.3, 121.9, 122.4,
128.1, 128.5, 128.8, 129.0, 129.3, 129.4, 129.5, 133.1,
135.1, 138.2, 148.8, 154.0, 158.5, 159.4, 162.7, 196.5 ppm;
MS (ESI): m/z = 512.12 ([M?1]?).
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(4-fluorophenyl)-
1H-pyrazol-4-yl]-7-methyl-5-oxo-4,5-dihydropyrano[4,3-
b]pyran-3-carbonitrile (7b, C26H16FN5O3S)
Yellow powder; yield 78%; m.p.: 215 °C; IR (KBr):
ꢀ
m = 3435, 3350 (asym., sym. str. of NH2), 2190 (C:N
1
str.), 1690 (C=O str.), 1230 (Ar–C–F str.) cm-1; H NMR
(400 MHz, DMSO-d6): d = 2.40 (s, 3H, CH3) 4.45 (s, 1H,
H4), 6.97 (s, 2H, NH2), 7.10–8.66 (m, 8H, Ar–H), 8.76 (s,
1H, pyrazole H5) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.4, 27.1, 57.8, 105.2, 112.7, 115.2, 116.9, 122.0,
122.7, 123.1, 124.9, 127.8, 128.8, 129.6, 131.4, 133.3,
133.4, 136.1, 148.9, 152.6, 153.9, 159.7, 160.7, 161.3 ppm;
MS (ESI): m/z = 498.10 ([M?1]?).
potassium bromide pellets in the range 4000–400 cm-1
,
and frequencies of only characteristic peaks are expressed
in cm-1. Elemental analysis (% C, H, N) was carried out
using a PerkinElmer 2400 series-II elemental analyzer
(PerkinElmer, USA), and all compounds were within
2-Amino-4-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-
yl]-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-
carbonitrile (7c, C29H16FN5O3S)
1
0.4% of the theoretical compositions. H NMR and 13C
NMR spectra were recorded in DMSO-d6 on a Bruker
Avance 400F (MHz) spectrometer (Bruker Scientific
Corp., Ltd., Switzerland) using TMS as an internal stan-
dard at 400 and 100 MHz, respectively. Chemical shifts
are reported in parts per million (ppm). Splitting patterns
are designated as s for singlet, d for doublet, and m for
multiplet. The ESI mass spectra were scanned on a Shi-
madzu LCMS 2010 spectrometer (Shimadzu, Tokyo,
Japan).
Light yellow powder; yield 73%; m.p.: 221 °C; IR (KBr):
ꢀ
m = 3455, 3289 (asym., sym. str. of NH2), 2194 (C:N
1
str.), 1683 (C=O str.), 1228 (Ar–C–F str.) cm-1; H NMR
(400 MHz, DMSO-d6): d = 4.75 (s, 1H, H4), 7.21–7.89
(m, 14H, Ar–H?NH2), 8.80 (s, 1H, pyrazole H5) ppm; 13
C
NMR (100 MHz, DMSO-d6): d = 27.3, 57.9, 103.3, 113.7,
115.8, 116.1, 117.1, 122.0, 122.7, 123.1, 125.1, 127.6,
128.6, 129.5, 131.2, 131.3, 133.2, 133.4, 135.3, 148.9,
152.5, 153.5, 154.0, 158.0, 159.2, 160.4, 161.6 ppm; MS
(ESI): m/z = 534.05 ([M?1]?).
General procedure for the synthesis of fused pyran
derivatives 7a–7t
In the typical experimental procedure, equimolar amounts
of 1-(substituted benzo[d]thiazol-2-yl)-3-(substituted phe-
nyl)-1H-pyrazole-4-carbaldehyde 5a–5d, compounds 6a–
6e, malononitrile, and a catalytic amount of pyrrolidine-
acetic acid were placed in the vessel of a microwave
reactor and irradiated under microwave for 5–7 min at
350 W output power. Completion of the reaction was
confirmed by TLC. After easy isolation of the obtained
product, it was purified by recrystallization with methanol
6-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(4-fluorophenyl)-
1H-pyrazol-4-yl]-3-methyl-1,4-dihydropyrano[2,3-c]pyra-
zole-5-carbonitrile (7d, C24H16FN7OS)
White powder; yield 68%; m.p.: 214 °C; IR (KBr):
ꢀ
m = 3450, 3292 (asym., sym. str. of NH2), 2204 (C:N
str.), 1232 (Ar–C–F str.) cm-1 1H NMR (400 MHz,
;
DMSO-d6): d = 1.81 (s, 3H, pyran), 4.93 (s, 1H, H4), 6.87
(s, 2H, NH2), 7.32 (m, 8H, Ar–H), 8.55 (s, 1H, pyrazole
H5), 12.03 (s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-
123

H. B. Patel et al.
d6): d = 10.2, 27.6, 56.5, 96.9, 121.2, 121.9, 122.6, 126.7,
128.4, 128.6, 129.1, 129.2, 133.0, 135.0, 136.0, 138.2,
149.0, 154.2, 154.9, 159.3, 161.3 ppm; MS (ESI):
m/z = 470.15 ([M?1]?).
14H, Ar–H?NH2), 8.81(s, 1H, pyrazole H5) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 21.4, 27.2, 57.8, 103.3,
113.7, 115.8, 115.9, 117.0, 121.9, 122.5, 122.9, 125.0,
127.5, 128.6, 129.2, 130.9, 131.2, 132.9, 133.2, 135.1,
148.8, 152.6, 153.5, 154.0, 158.0, 159.2, 160.4, 161.6 ppm;
MS (ESI): m/z = 530.05 ([M?1]?).
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(4-fluorophenyl)-
1H-pyrazol-4-yl]-5,10-dioxo-5,10-dihydro-4H-benzo[g]-
chromene-3-carbonitrile (7e, C30H16FN5O3S)
6-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(p-tolyl)-1H-pyra-
zol-4-yl]-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-
carbonitrile (7i, C25H19N7OS)
Light yellow powder; yield 75%; m.p.: 219 °C; IR (KBr):
ꢀ
m = 3452, 3290 (asym., sym. str. of NH2), 2201 (C:N
1
str.), 1679 (C=O str.), 1230 (Ar–C–F str.) cm-1; H NMR
Light yellow powder; yield 73%; m.p.: 214 °C; IR (KBr):
ꢀ
(400 MHz, DMSO-d6): d = 4.68 (s, 1H, H4), 7.29–8.06
(m, 14H, ArH?NH2), 8.73 (s, 1H, pyrazole H5) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 27.8, 58.1, 114.2, 114.9,
116.3, 116.8, 120.3, 122.3, 123.4, 125.3, 127.6, 128.6,
129.5, 131.2, 131.3, 133.2, 133.4, 135.3, 148.9, 152.5,
159.2, 160.4, 161.6, 163.1, 176.3, 181.4 ppm; MS (ESI):
m/z = 546.20 ([M?1]?).
m = 3453, 3295 (asym., sym. str. of NH2), 2193 (C:N
1
str.) cm-1; H NMR (400 MHz, DMSO-d6): d = 1.80 (s,
3H, CH3-pyran), 2.35 (s, 3H, CH3), 4.96 (s, 1H, H4), 6.86
(s, 2H, NH2), 7.21–8.11 (m, 8H, Ar–H), 8.63 (s, 1H,
pyrazole H5), 12.03 (s, 1H, NH) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 10.2, 21.4, 27.6, 56.5, 97.0,
121.2, 121.9, 122.5, 126.6, 128.2, 128.4, 129.1, 129.4,
133.0, 135.1, 136.0, 138.4, 149.0, 154.2, 154.9, 159.3,
161.3 ppm; MS (ESI): m/z = 466.12 ([M?1]?).
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(p-tolyl)-1H-pyra-
zol-4-yl]-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydro-4H-chro-
mene-3-carbonitrile (7f, C29H25N5O2S)
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(p-tolyl)-1H-pyra-
zol-4-yl]-5,10-dioxo-5,10-dihydro-4H-benzo[g]chromene-
3-carbonitrile (7j, C31H19N5O3S)
White powder; yield 83%; m.p.: 190 °C; IR (KBr):
ꢀ
m = 3455, 3292 (asym., sym. str. of NH2), 2203 (C:N
1
str.), 1682 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
White powder; yield 86%; m.p.: 224 °C; IR (KBr):
ꢀ
d6): d = 1.08 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.18 (s, 3H,
CH3), 2.21–2.54 (m, 4H, 2 9 CH2), 4.48 (s, 1H, H4), 7.03
(s, 2H, NH2), 7.32–7.98 (m, 8H, Ar–H), 8.51 (s, 1H,
pyrazole H5) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.4, 25.9, 28.0, 28.7, 32.1, 50.5, 58.3, 112.3, 121.9,
122.4, 128.1, 128.5, 128.8, 129.0, 129.2, 129.4, 129.6,
133.1, 135.1, 138.2, 148.8, 154.0, 158.4, 159.4, 162.7,
196.5 ppm; MS (ESI): m/z = 508.15 ([M?1]?).
m = 3450, 3290 (asym., sym. str. of NH2), 2200 (C:N
1
str.), 1682 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
d6): d = 2.36 (s, 3H, CH3), 4.66 (s, 1H, H4), 7.31–7.12 (m,
14H, Ar–H?NH2), 8.68 (s, 1H, pyrazole H5) ppm; 13C
NMR (100 MHz, DMSO-d6): d = 21.4, 27.8, 58.1, 114.4,
115.1, 116.4, 116.9, 120.5, 122.4, 123.6, 125.5, 127.8,
128.7, 129.5, 131.5, 131.4, 133.4, 133.7, 135.6, 149.1,
152.5, 159.2, 160.4, 161.5, 163.1, 176.3, 181.4 ppm; MS
(ESI): m/z = 542.05 ([M?1]?).
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(p-tolyl)-1H-pyra-
zol-4-yl]-7-methyl-5-oxo-4,5-dihydropyrano[4,3-b]pyran-
3-carbonitrile (7g, C27H19N5O3S)
2-Amino-4-[3-(4-fluorophenyl)-1-(6-methylbenzo[d]thia-
zol-2-yl)-1H-pyrazol-4-yl]-7,7-dimethyl-5-oxo-5,6,7,8-te-
trahydro-4H-chromene-3-carbonitrile
Yellow powder; yield 72%; m.p.: 221 °C; IR (KBr):
ꢀ
m = 3450, 3294 (asym., sym. str. of NH2), 2210 (C:N
(7k, C29H24FN5O2S)
White powder; yield 78%; m.p.: 228 °C; IR (KBr):
1
str.), 1684 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
ꢀ
d6): d = 2.34 (s, 3H, CH3), 2.41 (s, 3H), 4.47 (s, 1H, H5),
7.01 (s, 2H, NH2), 7.13-8.56 (m, 8H, Ar–H), 8.71 (s, 1H,
pyrazole H5) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.4, 21.4, 27.1, 57.8, 105.2, 112.7, 115.2, 116.9,
121.9, 122.7, 123.1, 125.0, 127.8, 128.8, 129.6, 131.4,
133.3, 133.4, 136.1, 149.0, 152.6, 154.0, 159.7, 160.7,
161.3 ppm; MS (ESI): m/z = 494.10 ([M?1]?).
m = 3455, 3294 (asym., sym. str. of NH2), 2207 (C:N
1
str.), 1682 (C=O str.), 1232 (Ar–C–F str.) cm-1; H NMR
(400 MHz, DMSO-d6): d = 1.02 (s, 3H, CH3), 1.09 (s, 3H,
CH3), 2.20 (s, 3H, CH3), 2.23–2.57 (m, 4H, 2 9 CH2), 4.45
(s, 1H, H4), 7.02 (s, 2H, NH2), 7.33–7.94 (m, 7H, Ar–H),
8.52 (s, 1H, pyrazole H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 21.3, 25.9, 28.0, 28.8, 32.1, 50.5, 58.3,
112.2, 121.9, 122.4, 128.1, 128.5, 128.8, 129.0, 129.2,
129.4, 129.5, 133.1, 135.1, 138.2, 148.8, 154.0, 158.4,
159.4, 162.7, 196.5 ppm; MS (ESI): m/z = 526.15
([M?1]?).
2-Amino-4-[1-(benzo[d]thiazol-2-yl)-3-(p-tolyl)-1H-pyra-
zol-4-yl]-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-car-
bonitrile (7h, C30H19N5O3S)
White powder; yield 83%; m.p.: 231 °C; IR (KBr):
mꢀ = 3451, 3289 (asym., sym. str. of NH2), 2190 (C:N
2-Amino-4-[3-(4-fluorophenyl)-1-(6-methylbenzo[d]thia-
zol-2-yl)-1H-pyrazol-4-yl]-7-methyl-5-oxo-4,5-dihydropy-
rano[4,3-b]pyran-3-carbonitrile (7l, C27H18FN5O3S)
1
str.), 1682 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
d6): d = 2.35 (s, 3H, CH3), 4.73 (s, 1H, H4), 7.23–8.10 (m,
123

Microwave-assisted solvent-free one-pot three-component synthesis of fused pyran derivatives…
Yellow powder; yield 75%; m.p.: 209 °C; IR (KBr):
160.4, 161.6, 163.1, 176.3, 181.4 ppm; MS (ESI):
m/z = 560.15 ([M?1]?).
ꢀ
m = 3448, 3290 (asym., sym. str. of NH2), 2201 (C:N
1
str.), 1678 (C=O str.), 1230 (Ar–C–F str.) cm-1; H NMR
2-Amino-7,7-dimethyl-4-[1-(6-methylbenzo[d]thiazol-2-
yl)-3-(p-tolyl)-1H-pyrazol-4-yl]-5-oxo-5,6,7,8-tetrahydro-
4H-chromene-3-carbonitrile (7p, C30H27N5O2S)
(400 MHz, DMSO-d6): d = 2.40 (s, 3H, CH3), 2.45 (s, 3H,
CH3-benzothiazole), 4.45 (s, 1H, H4), 6.98 (s, 2H, NH2),
7.09–8.62 (m, 7H, Ar–H), 8.75 (s, 1H, pyrazole H5) ppm;
13C NMR (100 MHz, DMSO-d6): d = 21.4, 27.1, 57.8,
105.2, 112.7, 115.2, 117.0, 122.0, 122.7, 123.1, 125.0,
127.8, 128.8, 129.6, 131.4, 133.3, 133.4, 136.1, 149.0,
152.6, 154.0, 159.7, 160.7, 161.3 ppm; MS (ESI):
m/z = 512.20 ([M?1]?).
Yellow powder; yield 79%; m.p.: 226 °C; IR (KBr):
ꢀ
m = 3453, 3291 (asym., sym. str. of NH2), 2194 (C:N
1
str.), 1676 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
d6): d = 1.08 (s, 3H, CH3), 1.12 (s, 3H, CH3), 2.20 (s, 3H,
CH3), 2.25–2.54 (7H, m, 2 9 CH2, 3H), 4.47 (s, 1H, H4),
7.01 (s, 2H, NH2), 7.31–7.93 (m, 7H, Ar–H), 8.48 (s, 1H,
pyrazole H5) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 21.4, 21.4, 25.9, 28.0, 28.7, 32.1, 50.5, 58.3, 112.3,
121.9, 122.5, 128.2, 128.6, 128.9, 129.0, 129.3, 129.4,
129.6, 133.1, 135.1, 138.5, 148.9, 154.2, 158.6, 159.3,
162.8, 196.5 ppm; MS (ESI): m/z = 522.20 ([M?1]?).
2-Amino-4-[3-(4-fluorophenyl)-1-(6-methylbenzo[d]thia-
zol-2-yl)-1H-pyrazol-4-yl]-5-oxo-4,5-dihydropyrano[3,2-
c]chromene-3-carbonitrile (7m, C30H18FN5O3S)
Yellow powder; yield 81%; m.p.: 196 °C; IR (KBr):
ꢀ
m = 3456, 3292 (asym., sym. str. of NH2), 2194 (C:N
1
str.), 1682 (C=O str.), 1229 (Ar–C–F str.) cm-1; H NMR
2-Amino-7-methyl-4-[1-(6-methylbenzo[d]thiazol-2-yl)-3-
(p-tolyl)-1H-pyrazol-4-yl]-5-oxo-4,5-dihydropyrano[4,3-
b]pyran-3-carbonitrile (7q, C28H21N5O3S)
(400 MHz, DMSO-d6): d = 2.43 (s, 3H, CH3-benzothia-
zole), 4.71 (s, 1H, H4), 7.29–7.87 (m, 13H, Ar–H?NH2),
8.82 (s, 1H, pyrazole H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 21.3, 27.2, 57.8, 103.2, 113.7, 115.8,
116.0, 116.9, 121.9, 122.6, 123.0, 124.9, 127.6, 128.6,
129.5, 131.1, 131.2, 133.1, 133.2, 135.2, 148.8, 152.5,
153.5, 153.9, 158.0, 159.2, 160.3, 161.6 ppm; MS (ESI):
m/z = 548.05 ([M?1]?).
White powder; yield 70%; m.p.: 215 °C; IR (KBr):
ꢀ
m = 3455, 3287 (asym., sym. str. of NH2), 2201 (C:N
1
str.), 1680 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
d6): d = 2.34 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.46 (s, 3H,
CH3-benzothiazole), 4.48 (s, 1H, H4), 6.99 (s, 2H, NH2),
7.11-8.20 (m, 7H, Ar–H), 8.78 (s, 1H, pyrazole H5) ppm;
13C NMR (100 MHz, DMSO-d6): d = 21.3, 21.4, 27.1,
57.8, 104.8, 112.1, 114.9, 116.9, 121.8, 122.2, 123.1,
124.9, 127.6, 128.4, 129.3, 131.1, 133.1, 133.1, 135.9,
148.8, 151.7, 153.9, 159.6, 160.7, 161.3 ppm; MS (ESI):
m/z = 508.15 ([M?1]?).
6-Amino-4-[3-(4-fluorophenyl)-1-(6-methylbenzo[d]thia-
zol-2-yl)-1H-pyrazol-4-yl]-3-methyl-1,4-dihydropy-
rano[2,3-c]pyrazole-5-carbonitrile (7n, C25H18FN7OS)
Light yellow powder; yield 75%; m.p.: 220 °C; IR (KBr):
ꢀ
m = 3449, 3296 (asym., sym. str. of NH2), 2210 (C:N
str.), 1230 (Ar–C–F str.) cm-1
;
1H NMR (400 MHz,
2-Amino-4-[1-(6-methylbenzo[d]thiazol-2-yl)-3-(p-tolyl)-
1H-pyrazol-4-yl]-5-oxo-4,5-dihydropyrano[3,2-c]chro-
mene-3-carbonitrile (7r, C31H21N5O3S)
DMSO-d6): d = 1.84 (s, 3H, CH3-pyran), 2.41 (s, 3H,
CH3-benzothiazole), 4.96 (s, 1H, H4), 6.87 (s, 2H, NH2),
7.21–8.34 (m, 7H, Ar–H), 8.67 (s, 1H, pyrazole H5), 12.07
(s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 10.2, 21.4, 26.7, 56.3, 96.7, 115.5, 115.7, 122.0,
122.4, 122.6, 126.3, 128.5, 128.9, 130.6, 130.7, 130.8,
132.9, 133.1, 135.0, 135.2, 148.9, 148.9, 161.3 ppm; MS
(ESI): m/z = 484.10 ([M?1]?).
Light yellow powder; yield 84%; m.p.: 223 °C; IR (KBr):
ꢀ
m = 3450, 3294 (asym., sym. str. of NH2), 2209 (C:N
1
str.), 1684 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
d6): d = 2.36 (s, 3H, CH3), 2.43 (s, 3H, CH3-benzothia-
zole), 4.71 (s, 1H, H4), 7.28–7.87 (m, 13H, Ar–H?NH2),
8.83 (s, 1H, pyrazole H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 21.4, 27.2, 57.8, 103.2, 113.7, 115.8,
116.0, 116.9, 119.6, 121.9, 122.6, 123.0, 124.9, 127.6,
128.6, 129.5, 131.1, 131.2, 133.1, 133.2, 135.2, 148.8,
152.5, 153.5, 153.9, 158.0, 159.2, 160.3, 161.6 ppm; MS
(ESI): m/z = 544.10 ([M?1]?).
2-Amino-4-[3-(4-fluorophenyl)-1-(6-methylbenzo[d]thia-
zol-2-yl)-1H-pyrazol-4-yl]-5,10-dioxo-5,10-dihydro-4H-
benzo[g]chromene-3-carbonitrile (7o, C31H18FN5O3S)
White powder; yield 70%; m.p.: 225 °C; IR (KBr):
ꢀ
m = 3457, 3288 (asym., sym. str. of NH2), 2203 (C:N
1
str.), 1682 (C=O str.), 1230 (Ar–C–F str.) cm-1; H NMR
6-Amino-3-methyl-4-[1-(6-methylbenzo[d]thiazol-2-yl)-3-
(p-tolyl)-1H-pyrazol-4-yl]-1,4-dihydropyrano[2,3-c]pyra-
zole-5-carbonitrile (7s, C26H21N7OS)
(400 MHz, DMSO-d6): d = 2.40 (s, 3H, CH3-benzothia-
zole), 4.70 (s, 1H, H4), 7.28–7.98 (m, 13H, Ar–H?NH2),
8.56 (s, 1H, pyrazole H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 21.3, 27.9, 57.9, 114.2, 115.0, 116.3,
116.7, 120.2, 122.2, 123.4, 125.4, 127.7, 128.7, 129.6,
131.4, 131.3, 133.3, 133.5, 135.4, 149.0, 152.5, 159.2,
Yellow powder; yield 76%; m.p.: 225 °C; IR (KBr):
mꢀ = 3440, 3288 (asym., sym. str. of NH2), 2200 (C:N
1
str.) cm-1; H NMR (400 MHz, DMSO-d6): d = 1.80 (s,
3H, CH3-pyran), 2.35 (s, 3H, CH3), 2.45(s, 3H, CH3-
123

H. B. Patel et al.
12.5 lg/cm3 concentration against all microorganisms;
10 mm3 suspension was further inoculated on appropriate
media, and growth was noted after 24 and 48 h. The con-
trol tube containing no antibiotic was instantaneously
subcultured by consistent spreading over an area of the
plate of medium fitting for the growth of the test organism.
The tubes were then incubated at 37 °C overnight. The
maximum dilution preventing the appearance of turbidity
after spot subculture was considered the minimal inhibitory
concentration (MIC). All the tubes showing no visible
growth (same as the control tube) were subcultured and
incubated overnight at 37 °C. The amount of growth in the
control tube before incubation was compared. In this study
ampicillin, norfloxacin, and ciprofloxacin were used as the
standard antibacterial drugs, while nystatin and griseoful-
vin were used as standard antifungal drugs.
benzothiazole), 4.95 (s, 1H, H4), 6.87 (s, 2H, NH2),
7.20–7.89 (m, 7H, Ar–H), 8.61 (s, 1H, pyrazole H5), 12.04
(s, 1H, NH) ppm; 13C NMR (100 MHz, DMSO-d6):
d = 10.2, 21.3, 21.5, 27.6, 56.5, 97.0, 121.2, 122., 122.6,
126.7, 128.5, 128.6, 129.3, 129.4, 133.1, 135.2, 135.9,
138.4, 148.9, 154.2, 154.9, 159.3, 161.3 ppm; MS (ESI):
m/z = 480.10 ([M?1]?).
2-Amino-4-[1-(6-methylbenzo[d]thiazol-2-yl)-3-(p-tolyl)-
1H-pyrazol-4-yl]-5,10-dioxo-5,10-dihydro-4H-benzo[g]-
chromene-3-carbonitrile (7t, C32H21N5O3S)
Yellow powder; yield 82%; m.p.: 213 °C; IR (KBr):
ꢀ
m = 3455, 3290 (asym., sym. str. of NH2), 2190 (C:N
1
str.), 1680 (C=O str.) cm-1; H NMR (400 MHz, DMSO-
d6): d = 2.37 (s, 3H, CH3), 2.42 (s, 3H, CH3-benzothia-
zole), 4.66 (s, 1H, H4), 7.30–8.03 (m, 13H, Ar–H?NH2),
8.61 (s, 1H, pyrazole H5) ppm; 13C NMR (100 MHz,
DMSO-d6): d = 21.3, 21.4, 27.8, 58.0, 114.1, 114.9, 116.3,
116.7, 120.1, 122.2, 123.4, 125.4, 127.7, 128.6, 129.5,
131.4, 131.3, 133.2, 133.4, 135.4, 148.9, 152.5, 159.2,
160.3, 161.5, 163.0, 176.2, 181.4 ppm; MS (ESI):
m/z = 556.15 ([M?1]?).
Acknowledgements The authors are thankful to the Head, Depart-
ment of Chemistry, Sardar Patel University, for providing 1H NMR
and 13C NMR spectroscopy and research facilities. We are also
thankful to the DST-Purse, Vallabh Vidyanagar, for providing the
mass spectrometry facilities. One of the authors, Jayvirsinh D. Gohil,
is grateful to UGC, New Delhi, for the Basic Science Research Fel-
lowship for Meritorious Students. Funding was provided by the
University Grants Commission (F-4-1/2006(BSR)/5-100/2007(BSR))
(E)-3-[[1-(Benzo[d]thiazol-2-yl)-3-(p-tolyl)-1H-pyrazol-4-
yl]methylene]naphthalene-1,2,4(3H)-trione
(8, C28H17N3O3S)
White powder; yield 79%; m.p.: 206 °C; 1H NMR
(400 MHz, DMSO-d6): d = 2.36 (s, 3H, CH3), 7.31–7.87
(m, 13H, Ar–H), 8.83 (s, 1H, pyrazole H5), 9.18 (s, 1H,
H4) ppm; 13C NMR (100 MHz, DMSO-d6): d = 21.4,
112.2, 115.7, 116.1, 116.9, 119.6, 121.5, 122.4, 123.2,
125.1, 126.2, 127.8, 128.6, 129.4, 131.1, 131.2, 132.5,
133.3, 133.7, 135.4, 149.0, 151.8, 159.2, 160.3, 161.6,
176.3, 178.5, 181.4 ppm; MS (ESI): m/z = 476.10
([M?1]?).
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