Bronsted acid-type biosurfactant for heterocyclization: A green protocol for benzopyran synthesis

Article abstract of DOI:10.1039/c5ra13652k

A natural biosurfactant, a biobased green acidic catalyst for cyclocondensation of salicylaldehyde (or 2-hydroxy naphthaldehyde) and cyclic 1,3-diketones for benzopyran synthesis in water has been reported for the first time. The structures of the final c

Full text of DOI:10.1039/c5ra13652k

RSC Advances
View Article Online
View Journal | View Issue
COMMUNICATION
Bronsted acid-type biosurfactant for
heterocyclization: a green protocol for benzopyran
Cite this: RSC Adv., 2015, 5, 84610
synthesis†
a
a
b
a
Received 12th July 2015
Accepted 29th September 2015
*
Smita T. Morbale, Swati D. Jadhav, Madhukar B. Deshmukh and Suresh S. Patil
DOI: 10.1039/c5ra13652k
www.rsc.org/advances
A natural biosurfactant, a biobased green acidic catalyst for cyclo-
Performing organic reactions in water have attracted much
condensation of salicylaldehyde (or 2-hydroxy naphthaldehyde) and attention over the past decades due to its numerous advantages
cyclic 1,3-diketones for benzopyran synthesis in water has been re- such as being considerably safe, nontoxic, environmental-
ported for the first time. The structures of the final compounds were friendly, and cheap.3–6 Nowadays, biosynthetic processes
confirmed with the aid of IR, 1H NMR, and 13C NMR spectroscopy. involving bio-based solvents or catalysts have received much
Lemon extract as a natural biosurfactant provides a micellar media for attention as a viable alternative for the development of green
effective organic transformation. The CMC of lemon extract was protocols for organic transformations.7
determined by the conductivity method. In comparison to the
In this regard, natural biosurfactants as part of the chemical
conventional methods, this synthetic pathway complies with several process offer an excellent alternatives to volatile organic
key requirements of green chemistry principles such as the utilization solvents in being more environmental-friendly technologies
of renewable feedstock, auxiliary aqueous conditions, waste preven- due to their ease of biodegradability, ability to act as catalysts,
tion, and atom economy along with the use of biodegradable catalyst. low toxicity, and non-ammable properties as compared to
Thus, the reported protocol offers an attractive option because of its chemical surfactants.8 Again, due to the high natural abun-
ecological safety, environmental acceptance, sustainability, and low- dance, their production is potentially less expensive.
cost straightforward work-up procedure.
The term ‘biosurfactant’ can be applied to a surfactant that
is obtained directly from a natural source (from plant, animal
or microbial cells) by some kind of separation procedure such
as extraction, precipitation or distillation. They form a part of
an emergent tool with a great potential for industrial appli-
cations including the use in enhanced oil recovery, crude oil
drilling, lubricants, health care and food processing industry.9
In addition to this, full evaluations of the potential of these
natural dispersants in cosmetic and soap formulations, foods
and dermal or transdermal drug delivery systems are devel-
oping at an incredible rate.10 It is notable that, despite their
diverse applications in industry and environmental biotech-
nology, their potential in accelerating the organic trans-
formations has not been evolved till this date.
Therefore, the aim of the present work is to explore the
synthetic utility of natural biosurfactant in organic trans-
formations. The catalytic medium is sourced from the direct
extraction of citrus fruit. From literature records it is well-known
that the citrus fruit locally known as Limbu (or Nimbu) in India;
it is a plant species commonly cultivated in a home garden or on
a farm and traditionally used for antioxidant activity.11 The power
of phytochemical, in a lemon which initiates varieties of chemical
transformations within biological systems is well-known.12,13
Polyphenolic avonoids in lemon, of which epigallocatechin
Introduction
While considering the increasing environmental pollution and
its intensive impact on living systems, the development of
chemical processes using more environmentally acceptable
chemicals, catalysts, solvents, atom-efficient methods, and
energy-efficient technologies eliminating waste production as
well as employing renewable raw materials is experiencing
a profound challenge to meet sustainability criteria.1 In addi-
tion, the environmental risks posed by the toxic and volatile
organic solvents have become a major concern. The reason is
that the organic transformations employ higher consumption
of solvents than the reagents and the employed solvents are
difficult to recycle;2 for the process to be in line with the green
chemistry principles, the rst task is to replace the organic
solvents with green ones.
aSynthetic Research Laboratory, PG Department of Chemistry, P.D.V.P. College, Dist.
Sangli, Tasgaon, 416312, India. E-mail: sanyujapatil@yahoo.com
bDepartment of Chemistry, Shivaji University, Kolhapur-416 004, India
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c5ra13652k
84610 | RSC Adv., 2015, 5, 84610–84620
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
Fig. 1 Structure of flavonoids and limonoids.
gallate (EGCG) is the major constituent, has anti-carcinogenic
To optimize the reaction conditions, 25 mL round bottom
activity.14,15 Phytochemical study showed the presence of limo- ask was charged with salicylaldehyde 1 (1.1 mmol), 1,3-
noids and avonoids16 (Fig. 1) which may collectively form dimedone 2 (2.2 mmol), lemon extract (3 mL) and the reaction
micelles and help to forward the reactions in proper direction. In mixture was stirred at room temperature as a model reaction.
addition to this lemon fruit extract exhibits acidic pH (2.3). In Aer 3 h low yield (30%) of corresponding product was
view of this data and in continuation of our ongoing research in observed on TLC (Table 1, entry 5). On increasing or
the development of green synthetic methodologies,17 we thought decreasing catalytic amount (1 to 5 mL), no signicant
that, this amazing medium may serve as Bronsted acid-type improvement in the result was obtained aer prolonged
biosurfactant, a better alternative to chemical surfactants and reaction time (Table 1, entries 1 to 7). We continued our efforts
also to harmful corrosive acids for organic transformations. for improvement in the result when model reactants were
Combined Bronsted acid surfactant catalysts in water have been allowed to react at elevated temperature (80 ꢀC), in presence of
employed in a number of organic reactions.18,19
3 mL lemon extract, aer 40 min, surprisingly the product was
obtained in 81% yield (Table 1, entry 8). In order to check and
verify further the effect of the solvent on the yield of the
product, the model reaction was performed in methanol,
ethanol, iso-propanol, t-butanol (Table 1, entry 9) which
afforded product in moderate yields. To our outmost expec-
tations, the reaction to perform in aqueous media, the reac-
tion proceeded very well, and 96% yield was obtained when
equi-volume quantity of lemon extract and water (3 mL each)
employed under identical conditions (Table 1, entry 10)
(Scheme 1). We also optimized the catalyst-solvent proportion
Results and discussion
At the beginning, we focused our attention on selection of citrus
fruit from different citrus species based on acidic pH. For this
purpose different fresh fruits were cut by using a knife and then
pieces were pressed manually using domestic presser to obtain
turbid extracts. The turbid extracts were then ltered through
cotton/muslin cloth and then through lter paper to remove
solid material to get clear extract. The pH of extracts were
measured using pH meter (ProLab 3000 laboratory pH meter)
and pH of Citrus limonium extract was found to be 2.3, which is
the lowest among all species, and therefore, it was used as acid
catalyst for this protocol.
The next task was to optimize different reaction parameters
for benzopyran synthesis. Benzopyran derivatives act as potas-
sium channel opener,20 PPAR a/g agonists,21 selective thrombin
(THR) inhibitors,22 anti-Helicobacter pylori agents.23 Benzopyr-
ans also exhibit insulin-sensitizing activities,24 antimicrobial
activities,25 and antibacterial activities.26
Recently some benzopyran derivatives have been synthesized
by the reaction of substituted salicylaldehydes with dimedone
using different catalysts such as KF/Al2O3,27 triethylbenzy-
lammonium chloride,28 2,4,6-trichloro-1,3,5-triazine,29 p-TSA30
and ionic liquid.31 These reported methods have their own
limitations such as low yield, less product selectivity and an
environmentally toxic catalyst. Considering these aspects, new
methodologies in mild reaction condition with a cheap and
easily available catalyst will be benecial as an interesting
challenge. Although diverse approaches towards the synthesis
of these derivatives have been developed, use of biosurfactant is
the most elegant strategy.
Table 1 Effect of catalytic amount of biosurfactant and temperature
on time and yield of the model reactiona
Amount of
Catalyst (mL)
Temp
(ꢀC)
Time
(min)
Yieldb
(%)
Entry
Solvent
1
2
3
4
5
6
7
8
9
1.0
1.5
2.0
2.5
3.0
4.0
5.0
3.0
3.0
—
—
—
—
—
—
—
—
RT
RT
RT
RT
RT
RT
RT
80
180
180
180
180
180
180
180
40
Trace
Trace
10
10
30
30
30
81
84,
MeOH
80
60
(87, 78, 72)c
96
10
11
12
13
14
3.0
3.0
4.0
5.0
—
Water
Waterd
Water
Water
Water
80
80
80
80
80
40
40
40
40
180
95, 88
93
90
Trace
a
Reaction conditions: salicylaldehyde 1 (1.1 mmol) and 1,3-dimedone 2
b
(2.2 mmol), solvent (3 mL). Isolated yield based on salicylaldehyde.
c
Ethanol, iso-propanol, t-butanol. d Water 4 and 5 mL.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 84610–84620 | 84611

View Article Online
RSC Advances
Communication
Scheme 1 Standard model reaction of salicylaldehyde and 1,3-dimedone.
Table 2 Comparison of efficiency of different biosurfactants for
for model reaction by changing catalyst-solvent ratio. The
result showed that 3 : 3 and 3 : 4 catalyst : solvent proportion
which is above the CMC composition (40% v/v) is a suitable
benzopyran synthesisa
Entry
Biosurfactant
pH
Time (min)
Yieldb (%)
medium for smooth conversion of reactant to the product with
respect to time and yield (entry 10 and 11). From these results,
it was also revealed that on further decreasing or increasing
the catalyst : solvent proportion reduces the yield of desired
product (entry 11–13). Moreover, the catalyst-free condition
was also examined; the result observed was viscous reaction
system and low yield which indicates that the role of bio-
surfactant is decisive for benzopyran 3 formation (Table 1,
entry 14).
1
2
3
4
5
6
Lemon extract
Lime extract
Pineapple extract
Grapefruit extract
Orange extract
Tangerine extract
2.30
2.40
3.71
3.38
3.51
3.90
40
90
90
100
90
60
96
92
73
79
65
60
a
Reaction conditions: salicylaldehyde 1 (1.1 mmol) and 1,3-dimedone 2
(2.2 mmol), biosurfactant : water (1 : 1 v/v), 80 ꢀC temperature.
b
Isolated yield based on salicylaldehyde.
On the completion of the reaction as monitored by TLC,
the product was separated out by simple ltration, succes-
sively washed with cold water, and recrystallized from 96%
ethanol which afforded the corresponding product of high
purity. Pure products obtained by recrystallization from
ethanol were characterized by their physical constants and
spectral techniques. In 1H NMR spectrum (Fig. 4a) of the
product of the model reaction (Table 3, entry 1), observation
of sharp singlet at d 10.50 due to enolic proton, and at d 4.65
corresponding to tertiary C–H proton as well as incorporation
of 23 signals in 13C NMR spectrum (Fig. 4b) supports its
formation. Further, in FT-IR spectrum (Fig. 4c), observation
of broad band due to enolic –OH at 3207 cmꢁ1 and at 1628
cmꢁ1 corresponding to a,b-unsaturated cyclic carbonyl group
supports its formation.
Thus, the acidic nature of fruit extracts as well as surface
activity due to avanoids and limonoids offered synergistic
effect, and reaction proceeded rapidly within short time. To
compare the catalytic activity of different natural surfactant
obtained from other fruit species, we also carried out the model
reaction using various other natural biosurfactants (Table 2,
entries 2–6). Surfactant obtained from Citrus limonium was
found to be excellent with respect to time as well as yield of the
product (Table 2, entry 1) suggesting that both the surfactant
property and strong Bronsted acidity of lemon extract are
essential to promote the reaction efficiency.
mixtures were ltered to isolate products and puried by
recrystallization from 96% ethanol. The reactions of salicy-
laldehydes, bearing electron-donating as well as electron-
withdrawing groups, underwent successfully.
Inspired by these tempting results obtained for cyclo-
condensation of benzopyran, we extended a same protocol for
treating various 1,3-diketones 2 with 2-hydroxy naphthaldehyde
4 (Scheme 2) and we found that these substrates also worked
very efficiently under this catalytic system (Table 4).
As discussed before, in the absence of the catalyst, the
reaction proceeded sluggishly which explains the role of cata-
lytic activity of biosurfactant in product formation. Under
ambient conditions, surfactant molecules can aggregate in an
aqueous phase to form micelles with hydrophobic core and
hydrophilic corona. The use of micellar surfactants as a catalyst
is widespread and has been investigated in detail for various
reactions in aqueous solutions.32 The role of micelle to catalyze
the reaction is schematically represented in Fig. 2a.
As the impact of micellar solution, hydrophobic reactants i.e.
salicylaldehyde and 1,3-diketones get pushed away from water
molecules towards the hydrophobic core of micelle leading to
the effective collisions and water formed by condensations is
repelled out to give corresponding Knoevenagel product 6,
which was further reacted with another molecule of 1,3-dike-
tones with shiing of equilibrium towards formation of desired
product 3 (Scheme 3) with excellent yield.
Aer optimization of reaction condition, the condensation
reactions were carried out in lemon extract : water (1 : 1, v/v) at
80 ꢀC in a preheated oil-bath using a series of structurally
diverse salicylaldehydes with 1,3-ketones (Table 3). On the
completion of reactions as monitored by TLC, the reaction
During the progress of the reaction, the reaction mixture
turned turbid due to the formation of colloidal aggregates
which was conrmed on the basis of optical microscopy
(Fig. 2b). At the critical micelle concentration (CMC) of
84612 | RSC Adv., 2015, 5, 84610–84620
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
Table 3 Biosurfactant catalysed synthesis of benzopyrana
Entry
Carbonyl compounds
Products
Time (min)
Yieldb (%)
1
40
96
2
45
80
3
45
92
4
5
6
30
30
30
91
91
90
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 84610–84620 | 84613

View Article Online
RSC Advances
Communication
Table 3 (Contd.)
Entry
Carbonyl compounds
Products
Time (min)
Yieldb (%)
7
60
87
8
55
84
9
45
40
45
88
93
94
10
11
12
50
91
13
60
87
84614 | RSC Adv., 2015, 5, 84610–84620
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
Table 3 (Contd.)
Entry
Carbonyl compounds
Products
Time (min)
Yieldb (%)
14
60
84
15
16
50
40
86
89
17
50
90
18
40
91
a
Reaction conditions: salicylaldehydes 1 (1.1 mmol) and 1,3-diketones 2 (2.2 mmol), biosurfactant (3 mL), water (3 mL), 80 ꢀC temperature.
Isolated yield based on salicylaldehyde.
b
Scheme 2 Reaction of 2-hydroxy naphthaldehyde and cyclic 1,3-diketones under optimized conditions.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 84610–84620 | 84615

View Article Online
RSC Advances
Communication
Table 4 Biosurfactant catalysed cyclocondensation of 2-hydroxy naphthaldehyde and cyclic 1,3-diketonesa
Entry
Carbonyl compounds
Products
Time (min)
Yieldb (%)
1
60
95
2
60
91
3
60
94
a
Reaction conditions: 2-hydroxy naphthaldehyde 4 (1.1 mmol) and cyclic 1,3-diketone 2 (2.2 mmol), biosurfactant (3 mL), water (3 mL), 80 ꢀC
temperature. b Isolated yield based on 2-hydroxy naphthaldehyde 5.
Then, we compared our catalytic data with that found in
the literature. Comparison of the results shows a better
catalytic activity of biosurfactant for synthesis of benzopyr-
ans (Table 5).
In summary, we have introduced
a highly efficient,
straightforward bioorganic approach for benzopyran synthesis
via Knoevenagel condensation and tandem Knoevenagel–
Michael reaction which represents eco-friendly and environ-
mental benign system. Simplicity of product separation, clean
reaction prole, and utilization of biodegradable catalyst ob-
tained from renewable resource provide attractive alternative to
the previously reported methodologies. Therefore, this new
acidic natural biosurfactant should thereby provide attractive
alternative to the harmful corrosive acids. We expect that the
methodology presented hereby will nd great utility in
academic and industrial applications in the near future.
Experimental
Fig. 2 (a) Mechanistic picture of role of micellae for benzopyran
formation. (b) Optical micrograph of model reaction mixture normal
view and magnified view.
All the chemicals were commercially sourced from Sigma
Aldrich and used without further purication. The melting
points were determined on DBK programmable melting point
apparatus and are uncorrected. Infrared spectra were measured
surfactant solutions, a drastic change occurs in physico-
chemical properties such as conductivity, surface tension,
turbidity etc.33 To maintain better lemon extract : water
composition for this cyclocondensation, we employed electrical
conductivity method to determine the critical micelle concen-
tration (CMC) and it was found to be 40% v/v (Fig. 3).
with a Bruker FT-IR spectrophotometer. The H NMR and 13C
1
1
NMR spectra were recorded on a Bruker AC (300 MHz for H
NMR and 300 MHz for 13C NMR) spectrometer using CDCl3 as
a solvent. The chemical shis are expressed in d parts per
million (ppm) values with tetramethylsilane (TMS) as the
84616 | RSC Adv., 2015, 5, 84610–84620
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
Scheme 3 Plausible mechanism for the reaction between salicylaldehyde 1 and 1,3-dimedone 2 catalyzed by acidic biosurfactant (H+/Aꢁ).
internal reference. The Equiptronics (Model EQ-664A) digital
auto ranging conductivity meter was used for the measurement
of critical micellar concentration. For the preparation of fruit
extract, fresh Citrus limonium fruits were obtained from the
local market, and species was authenticated by the Department
of Botany. The small pieces of a fruit was pressed manually by
domestic pressure to get turbid extract and ltered through
lter paper and muslin cloth to get clean, pale-yellow-colored
extract. This extract was stored below 5 ꢀC temperature and
found to be stable for several days.
Optical microscopy measurements: a drop of turbid reaction
mixture was subjected to light microscopy measurement using
an ordinary light microscope under 100ꢂ magnication.
Typical procedure for synthesis of 9-(2-hydroxy-4,4-dimethyl-6-
oxo-cyclohex-1-enyl)-3,3-dimethyl-2,3,4,9-tetrahydroxanthen-
1-one
Fig. 3 Critical micellar concentration (CMC) obtained from plot of
specific conductance against percentage composition of
In a 25 mL round bottom ask, salicylaldehyde (1.1 mmol), 1,3-
dimedone (2.2 mmol) were placed in lemon extract : water
(6 mL, 1 : 1, v/v) and reaction mixture was stirred at 80 ꢀC
biosurfactant.
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 84610–84620 | 84617

View Article Online
RSC Advances
Communication
Table 5 Comparison of biosurfactant with other catalysts in the literature to synthesize benzopyran
Sr. no.
Catalyst
Solvent
Reaction condition
Yield (%)
References
1
2
3
4
5
6
KF/Al2O3
Ethanol
Water
Solvent free
Solvent free
Water
80 ꢀC, 0.25 gm
83
86
96
93
83
96
27
28
Triethylbenzylammoium chloride (TEBA)
Cellulose sulfuric acid
2,4,6-Trichloro-1,3,5-triazine
p-TSA
90 ꢀC, 0.1 g, 5 h
RT, 0.08 g, grinding, 30 min
120 ꢀC, 10 mol%, 2.5 h
90 ꢀC, 10 mol%, 30 min
80 ꢀC, 3 mL, 40 min
28 (cross ref.)
29
30
Lemon juice
Water
Present work
Fig. 4 (a) 1H NMR (CDCl3) spectrum of compound 3a. (b) 13C NMR (CDCl3) spectrum of compound 3a. (c) FT-IR spectrum of the compound 3a.
temperature in preheated oil-bath till the completion of reac- 2H, –CH2), 3.88 (s, 1H, –OCH3), 1.14 (s, 3H, –CH3), 0.93 (s, 9H,
tion as indicated by TLC (ethylacetate : hexane 4 : 6). The solid 3CH3); 13C NMR (300 MHz, CDCl3): 200.40, 196.521, 170.554,
products was separated by simple ltration through a Buchner 168.800, 147.081, 140.658, 125.203, 124.203, 119.760, 118.149,
funnel, washed with cold water, and recrystalyzed from 96% 110.887, 110.370, 56.058, 50.623, 49.930, 43.167, 41.533, 32.288,
ethanol (5 mL). The identity of the compound was ascertained 30.887, 29.852, 29.051, 27.755, 27.162, 26.421.
on the basis of 1H NMR, 13C NMR, and FT-IR spectroscopy
7-Bromo-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-
(Fig. 4a–c). The physical and spectroscopic data are in consis- dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (Table 3, entry 3).
tent with the proposed structure and is in harmony with the Yield: 92%; mp 248–251 ꢀC; 1H NMR (300 MHz, CDCl3): d 10.15
literature values.
(s, 1H, –OH), 7.21–7.24 (dd, J ¼ 1.9, 6.8 Hz, 1H, Ar–H), 7.08 (s,
Physical and spectroscopic data of selected compounds are 1H, Ar–H), 6.87 (d, J ¼ 8.7 Hz, 1H, Ar–H), 5.02 (s, 1H, –CH–),
as follow:
2.28–2.59 (m, 6H, 3-CH2), 1.95 (s, 2H, –CH2), 1.33 (s, 3H, –CH3),
9-(2-Hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-dimethyl- 0.99–1.05 (m, 9H, 3-CH3); 13C NMR (300 MHz, CDCl3 + DMSO):
1
ꢀ
2,3,4,9-tetrahydroxanthen-1-one. Yield: 96%; mp 215–218 C; H d 195.65, 164.328, 148.794, 130.563, 129.103, 127.741, 116.932,
NMR (300 MHz, CDCl3): d 10.50 (s, 1H, –OH), 7.08–7.16 (m, 1H, 115.413, 110.34, 50.27, 40.65, 40.33, 40.05, 39.78, 39.22, 38.94,
Ar–H), 6.93–7.01 (m, 3H, Ar–H), 4.65 (s, 1H, –CH), 2.54 (q, J ¼ 17.7, 38.66, 31.35, 31.27, 28.93, 27.56, 26.30; IR (cmꢁ1): 3103, 2963,
20.0 Hz, 2H, –CH2), 2.35 (s, 2H, –CH2), 2.30 (s, 2H, –CH2), 1.93 (q, J 1618, 1475, 1374, 1302, 1231, 1178, 1075, 1037, 884, 817, 657,
¼ 6.0, 16.4 Hz, 2H, –CH2), 1.14 (s, 3H, –CH3), 1.03 (s, 3H, –CH3), 590, 478; MS: 445 (M + 1), 447 (M + 2). Anal. calcd for
1.00 (s, 6H, 2-CH3); 13C NMR (300 MHz, CDCl3): d 200.40, 196.13,
C23H25BrO4: C, 62.03; H, 5.66; Br, 17.94; O, 14.37. Found: C,
170.53, 168.78, 151.04, 127.98, 127.52, 124.53, 118.31, 115.78, 62.03; H, 5.65. HRMS m/z calcd for: C23H25BrO4: 445.0000,
111.07, 96.20, 50.58, 49.93, 43.24, 41.60, 32.33, 31.02, 29.85, 29.43, found 445.1003 (M)+.
27.79, 27.21, 26.42; IR (cmꢁ1): 3153, 2958, 1622, 1488, 1376, 1312,
7-Chloro-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)-3,3-
1233, 1185, 1151, 1077, 1019, 762, 655, 582, 475; MS: 367 (M + 1), dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (Table 3, entry 5).
389 (M + Na). Anal. calcd for C23H26O4: C, 75.38; H, 7.15; O, 17.46. Yield: 91%; mp 232–234 ꢀC; 1H NMR (300 MHz, CDCl3): d 10.50
Found: C, 75.33; H, 7.15; HRMS m/z calcd for C23H26O4: 366.0000, (s, 1H, –OH), 7.09 (dd, J ¼ 2.2, 2.6 Hz, 1H, Ar–H), 6.91–6.97 (m,
found 367.1918 (M + H), 389.1737 (M + Na).
2H, Ar–H), 4.61 (s, 1H, –CH), 2.52 (q, J ¼ 17.3, 18.5 Hz, 2H,
3-Methoxy-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1-enyl)- –CH2), 2.37 (d, J ¼ 4.9 Hz, 2H, –CH2), 2.30 (s, 2H, –CH2), 1.96 (s,
3,3-dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (Table 3, entry 2H, –CH2), 1.14 (s, 3H, –CH3), 1.00–1.05 (m, 9H, 3-CH3); IR
2). Yield: 80%; mp 224–227 ꢀC; 1H NMR (300 MHz, CDCl3): (cmꢁ1): 3102, 2965, 2710, 1624, 1571, 1476, 1374, 1301, 1233,
d 10.50 (s, 1H, –OH), 7.08–7.21 (m, 1H, Ar–H), 6.93–7.01 (m, 3H, 1179, 1077, 1038, 1015, 879, 819, 657, 618, 591, 549, 469; MS:
Ar–H), 4.63 (s, 1H, –CH), 2.54 (q, J ¼ 17.7, 20.0 Hz, 2H, –CH2), 401 (M + 1), 403 (M + 2). Anal. calcd for C23H25ClO4: C, 68.91; H,
2.35 (s, 2H, –CH2), 2.30 (s, 2H, –CH2), 1.93 (q, J ¼ 6.0, 16.4 Hz, 6.29; Cl, 8.84; O, 15.96. Found: C, 68.89; H, 6.24. HRMS m/z
84618 | RSC Adv., 2015, 5, 84610–84620
This journal is © The Royal Society of Chemistry 2015

View Article Online
Communication
RSC Advances
calcd for C23H25ClO4: 400.0000, found 401.1529 (M + H), 39.77, 39.50, 39.2, 38.94, 38.76, 31.45, 31.3, 28.97, 27.56, 26.69,
423.1328 (M + Na).
26.20, 25.75, 29; IR (cmꢁ1): 49, 2887, 2526, 1651, 1560, 1452,
5-Bromo-7-chloro-9-(2-hydroxy-4,4-dimethyl-6-oxo-cyclohex-1- 1363, 1279, 1245, 1185, 1133, 1063, 1007, 857, 765, 707, 538,
enyl)-3,3-dimethyl-2,3,4,9-tetrahydro-xanthen-1-one (Table 3, 500, 438; MS: 423 (M+), 425 (M+2) anal. calcd for C19H16BrClO4:
entry 6). Yield: 90%; mp 241–243 ꢀC; 1H NMR (300 MHz, CDCl3): C, 53.86; H, 3.81; Br, 18.86; Cl, 8.37; O, 15.11, found: C, 53.85;
d 10.34 (s, 1H, –OH), 7.36 (d, J ¼ 2.2 Hz, 1H, Ar–H), 6.90 (d, J ¼ H, 3.81.
2.0 Hz, 1H, Ar–H), 4.60 (s, 1H, –CH), 2.62 (q, J ¼ 17.7, 18.5 Hz,
5-Methoxy-2,3-dihydro-9-(2-hydroxy-5-oxocyclopent-1-enyl)-
2H, –CH2), 2.38 (d, J ¼ 4.5 Hz, 2H, –CH2), 2.31 (s, 2H, –CH2), 1.97 cyclopenta[b]chromen-1(9H)-one (Table 3, entry 14). Yield:
(s, 2H, –CH2), 1.16 (s, 3H, –CH3), 1.00–1.05 (m, 9H, 3-CH3); 13 84%; mp 257–260 ꢀC; 1H NMR (300 MHz DMSO): 2.29–2.36 (m,
C
NMR (300 MHz, CDCl3): d 196.47, 195.10, 163.43, 144.77, 6H, 3CH2), 2.72–2.74 (m, 2H, CH2), 3.82 (s, 3H, CH3O), 4.58 (s,
128.68, 127.79, 127.41, 126.35, 112.78, 109.93, 108.78, 94.79, 1H, CH), 6.58–6.60 (m, 1H, ArH), 6.92 (dd, J ¼ 8.0 Hz, J ¼ 1.2 Hz,
49.58, 49.03, 39.81, 30.77, 28.24, 26.92, 26.03, 25.64, 25.17; IR 1H, ArH), 6.99–7.03 (m, 1H, ArH), 11.80 (b, 1H, OH); IR (cmꢁ1):
(cmꢁ1): 3184, 2940, 1647, 1599, 1452, 1375, 1313, 1257, 1207, 3438, 3024, 2971, 2939, 1682, 1637, 1579, 1480, 1445, 1380,
1183, 1150, 1017, 887, 855, 803, 722, 662, 587, 475; MS: 479 (M+), 1322, 1273, 1255, 1237, 1170, 1125, 1076, 825, 788, 739, 716.
481 (M + 2). Anal. calcd for C23H24BrClO4: C, 57.58; H, 5.04; Br,
7-Bromo-2,3-dihydro-9-(2-hydroxy-5-oxocyclopent-1-enyl)-
16.65; Cl, 7.39; O, 13.34. Found: C, 57.57; H, 5.04; HRMS m/z cyclopenta[b]chromen-1(9H)-one (Table 3, entry 15). Yield:
calcd for C23H23ClBrO4: 478.0000, found 479.0618 (M + H), 86%; mp 280–282 ꢀC; 1H NMR (300 MHz DMSO): 2.26–2.43 (m,
481.0602 (M + 2) 501.0421 (M + Na), 503.0415 (M + Na + 2).
6H, 3CH2), 2.56–3.34 (m, 2H, CH2), 5.01 (s, 1H, CH), 7.01–7.24
9-(2-Hydroxy-6-oxo-cyclohex-1-enyl)-2,3,4,9-tetrahydro-xanthen- (m, 2H, ArH), 7.27 (d, J ¼ 8.4 Hz, 1H, ArH), 10.60 (b, 1H, OH); IR
1-one (Table 3, entry 7). Yield: 87%; mp 240–243 ꢀC; 1H NMR (300 (cmꢁ1): 3505, 2932, 2910, 1699, 1653, 1585, 1474, 1383, 1276,
MHz, CDCl3): d 10.00 (s, 1H, –OH), 6.80–7.14 (m, 4H, Ar–H), 4.84 1259, 1240, 1198, 1160, 1126, 1071, 1018, 818, 707, 659.
(s, 1H, –CH), 1.60–2.40 (m, 12H, 6-CH2); IR (cmꢁ1): 2951, 2538,
7-Nitro-2,3-dihydro-9-(2-hydroxy-5-oxocyclopent-1-enyl)cyclo-
1830, 1641, 1553, 1485, 1421, 1372, 1294, 1235, 1192, 1142, 1071, penta[b]chromen-1(9H)-one (Table 3, entry 16). Yield: 89%; mp
993, 924, 850, 773, 564, 493 MS: 311 (M + 1). Anal. calcd for 265–268C ꢀC; 1H NMR (300 MHz DMSO): 2.34–2.41 (m, 6H,
C19H18O4: C, 73.53; H, 5.85; O, 20.62. Found: C, 73.52; H, 5.84; 3CH2), 2.74–2.76 (m, 2H, CH2), 4.72 (s, 1H, CH), 7.41 (d, J ¼ 8.8
HRMS m/z calcd for C19H18O4: 310.0000, found 311.1295 (M + H), Hz, 1H, ArH), 7.87 (d, J ¼ 2.4 Hz, 1H, ArH), 8.11 (dd, J ¼ 8.8 Hz, J
333.1081 (M + Na).
¼ 2.4 Hz, 1H, ArH), 12.06 (b, 1H, OH). IR (cmꢁ1): 3512, 2943,
7-Bromo-9-(2-hydroxy-6-oxo-cyclohex-1-enyl)-2,3,4,9-tetrahydro- 2926, 1698, 1656, 1581, 1528, 1481, 1458, 1379, 1277, 1253, 1168,
xanthen-1-one (Table 3, entry 9). Yield: 88%; mp 238–240 C; H 1134, 1020, 929, 912, 840, 805, 748, 666.
1
ꢀ
NMR (300 MHz): d 10.75 (s, 1H, –OH), 7.25 (d, J ¼ 3.0 Hz, 1H, Ar–
7-Chloro-2,3-dihydro-9-(2-hydroxy-5-oxocyclopent-1-enyl)cyclo-
H), 7.09 (d, J ¼ 2.2 Hz, 1H, Ar–H), 6.89 (dd, J ¼ 5.2, 6.0 Hz, 1H, Ar– penta[b]chromen-1(9H)-one (Table 3, entry 17). Yield: 90%; mp
H), 4.57 (s, 1H, –CH), 1.76–2.85 (m, 12H, 6-CH2); 13C NMR (300 271–273 ꢀC; 1H NMR (300 MHz DMSO): 2.33–2.38 (m, 6H, 3CH2),
MHz, CDCl3): 202.18, 193.99, 167.43, 166.15, 148.45, 129.74, 2.71–2.73 (m, 2H, CH2), 4.60 (s, 1H, CH), 7.01 (dd, J ¼ 2.4 Hz, J ¼
129.28, 128.61, 126.86, 116.51, 116.10, 115.09, 47.57, 35.57, 35.02, 1.2 Hz, 1H, ArH), 7.18 (d, J ¼ 8.8 Hz, 1H, ArH), 7.27–7.30 (m, 1H,
33.26, 26.02, 22.80, 18.95; IR (cmꢁ1): 3105, 2955, 1640, 1596, 1477, ArH), 12.00 (b, 1H, OH); IR (cmꢁ1): 3508, 2935, 2914, 1699, 1654,
1374, 1279, 1233, 1186, 1144, 1070, 981, 819, 763, 620, 530, 470; 1583, 1477, 1409, 1384, 1277, 1259, 1240, 1162, 1126, 1018, 819,
MS: 389 (M + 1) 391 (M + 2); anal. calcd. For C19H17BrO4: C, 58.63; 677.
H, 4.40; Br, 20.53; O, 16.44, found: C, 58.63; H, 4.39; HRMS m/z
7,8-h-ph-9-(2-Hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)-
calcd for C19H17BrO4: 389.0000, found 391.0551 (M + 2).
3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-one (3h) (Table 4,
7-Chloro-9-(2-hydroxy-6-oxo-cyclohex-1-enyl)-2,3,4,9-tetrahydro- entry 1). Yield: 95% mp 235–237 ꢀC. 1H NMR (300 MHz, CDCl3)
xanthen-1-one (Table 3, entry 11). Yield: 94%; mp 242–244 ꢀC; 1H d ¼ 10.70 (s, 1H, OH), 7.78 (d, 1H, ArH), 7.73 (d, 2H, ArH), 7.48
NMR (500 MHz, CDCl3): d 10.76 (s, 1H, –OH), 7.09 (d, J ¼ 6.3 Hz, (t, 1H, ArH), 7.39 (t, 1H, ArH), 7.27 (d, 1H, ArH), 5.27 (s, 1H,
1H, Ar–H), 6.91–6.96 (m, 2H, Ar–H), 4.57 (s, 1H, –CH), 1.77–2.81 CH), 2.68 (ABq, J ¼ 17.6 Hz, 1H, CH2), 2.57 (ABq, J ¼ 17.6 Hz,
(m, 12H, 6-CH2); 13C NMR (300 MHz, CDCl3 + DMSO-d6): 201.86, 1H, CH2), 1.96 (ABq, J ¼ 16.4 Hz, 1H, CH2), 1.83 (ABq, J ¼ 16.4
193.94, 167.23, 165.96, 147.56, 127.13, 126.76, 125.61, 124.53, Hz, 1H, CH2), 2.36–2.41 (m, 4H, 4CH2), 1.17 (s, 3H, CH3), 1.08
115.52, 110.65, 99.74, 47.08, 35.47, 34.82, 33.05, 26.35, 22.69, (s, 3H, CH3), 0.95 (s, 3H, CH3), 0.72 (s, 3H, CH3) ppm; 13C NMR
19.03; IR (cmꢁ1): 3110, 2954, 1645, 1596, 1477, 1416, 1375, 1280, (300 MHz, CDCl3) d ¼ 201.11, 196.85, 170.22, 169.09, 148.89,
1239, 1188, 1141, 1068, 984, 917, 824, 576, 460; MS: 345 (M+), 347 131.26, 130.96, 158.54, 128.50, 126.71, 124.64, 122.87, 117.68,
(M + 2). Anal. calcd for C19H17ClO4: C, 66.19; H, 4.97; Cl, 10.28; O, 116.59, 116.14, 111.08, 50.71, 49.98, 43.18, 41.37, 32.42, 30.62,
18.56, found: C, 66.18; H, 4.97.
29.92, 29.33, 27.10, 26.37, 25.38 ppm; IR (KBr): 3182, 2941,
5-Bromo-7-chloro-9-(2-hydroxy-6-oxo-cyclohex-1-enyl)-2,3,4,9- 2862, 1643, 1593, 1464, 1373, 1315, 1261, 1235, 1061, 1026,
tetrahydro-xanthen-1-one (Table 3, entry 12). Yield: 91%; mp 888, 813 cmꢁ1
.
1
ꢀ
238–240 C; H NMR (300 MHz, CDCl3): d 10.44 (s, 1H, –OH),
7.30 (d, J ¼ 2.6 Hz, 1H, Ar–H), 6.95 (d, J ¼ 1.7 Hz, 1H, Ar–H),
Conclusions
5.04 (s, 1H, –CH), 1.93–2.12 (m, 4H, 2-CH2), 2.25–2.51 (m, 8H,
4-CH2); 13C NMR (300 MHz, CDCl3): 195.44, 163.90, 145.45, In conclusion, we developed a simpler, more convenient, and
129.31, 128.72, 127.93, 110.62, 109.50, 50.29, 40.33, 40.05, more efficient procedure for synthesis of benzopyran from the
This journal is © The Royal Society of Chemistry 2015
RSC Adv., 2015, 5, 84610–84620 | 84619

View Article Online
RSC Advances
Communication
various salicylaldehydes (or 2-hydroxy naphthaldehyde) and 15 O. J. Bandele and N. Osheroff, Chem. Res. Toxicol., 2008, 21,
cyclic 1,3-diketones using catalytic amount of lemon extract as 936–943.
a green biosurfactant under mild reaction conditions. The use 16 G. Gattuso, D. Barreca, C. Gargiulli, U. Leuzzi and C. Caristi,
of the low-cost, biodegradable biosurfactant in replacement to Molecules, 2007, 12, 1641–1673.
toxic synthetic surfactants is a promising alternative for the 17 (a) S. S. Patil, S. D. Jadhav and M. B. Deshmukh, J. Chem. Sci.,
organic transformations. Usability of the catalyst in aqueous
medium caters to a more ‘green’ and eco-friendly solution
towards benzopyran formation.
2013, 125, 851–857; (b) M. B. Deshmukh, S. S. Patil,
S. D. Jadhav and P. B. Pawar, Synth. Commun., 2012, 42(8),
1177–1183.
18 (a) K. Manabe, Y. Mori and S. Kobayashi, Synlett, 1999, 1401–
1402; (b) K. Manabe, Y. Mori and S. Kobayashi, Tetrahedron,
2001, 57, 2537–2544; (c) K. Manabe and S. Kobayashi, Org.
Lett, 1999, 1, 1965–1967; (d) K. Manabe, Y. Mori,
T. Wakabayashi, S. Nagayama and S. Kobayashi, J. Am.
Chem. Soc., 2000, 122, 7202–7207.
Acknowledgements
We acknowledge the UGC New Delhi for the nancial assistance
and to the Director, IICT, Hyderabad, India, for providing
necessary instrumental facilities.
19 (a) T. Akiyama, J. Takaya and H. Kagoshima, Tetrahedron
Lett., 1999, 40, 7831–7834; (b) T. Akiyama, J. Takaya and
H. Kagoshima, Synlett, 1999, 1426–1428.
20 R. C. Gadwood, B. V. Kamdar, L. A. C. Dubray, M. L. Wolfe,
M. P. Smith, W. Watt, S. A. Mizsak and V. E. Groppit, J.
Med. Chem., 1995, 36, 1480–1487.
References
1 P. Anastas and J. Warner, Green Chemistry: Theory and
Practice, Oxford University Press, New York, 1998, p. 30;
J. H. Clark, Green Chem., 1999, 1, 1–8.
2 R. A. Sheldon, Green Chem., 2005, 7, 267–278.
3 R. Breslow, Acc. Chem. Res., 1991, 24, 159–164.
4 J. B. F. N. Engberts and M. J. Blandamer, Chem. Commun.,
2001, 1701–1708.
5 S. Kobayashi and K. Manabe, Pure Appl. Chem., 2000, 72,
1373–1380.
21 J. Yu, L. Tang, Y. Tang and R. Ji, Eur. J. Med. Chem., 2008, 43,
2428–2435.
22 R. Frederick, S. Robert, C. Charlier, J. Wouters, B. Masereel
and L. Pochet, J. Med. Chem., 2007, 50, 3645–3650.
23 F. Chimenti, B. Bizzarri, A. Bolasco, D. Secci, P. Chimenti,
S. Carradori, A. Granese, D. Rivanera, D. Lilli,
M. M. Scaltrito and M. I. Brenciaglia, Eur. J. Med. Chem.,
2006, 41, 208–212.
¨
6 U. M. Lindstrom, Chem. Rev., 2002, 102, 2751–2772.
7 (a) M. Li, C. Chen, F. He and Y. Gu, Adv. Synth. Catal., 2010,
352, 519–530; (b) D. M. Alonso, J. Q. Bond and J. A. Dumesic,
24 L. Tang, J. Yu, Y. Leng, Y. Feng, Y. Yang and R. Ji, Bioorg.
Med. Chem. Lett., 2003, 13, 3437–3440.
´ ˆ
Green Chem., 2010, 12, 1493–1513; (c) Y. Gu and F. Jerome,
Chem. Soc. Rev., 2013, 42, 9550–9570; (d) S. Sun, R. Bai and
Y. Gu, Chem.–Eur. J., 2014, 20, 549–558; (e) F. He, P. Li,
Y. Gu and G. Li, Green Chem., 2009, 11, 1768–1773; (f)
B. Zhou, J. Yang, M. Li and Y. Gu, Green Chem., 2011, 13,
2204–2211.
25 H. M. Shaaer, P. Foltinova, M. Lacova, J. Chovancova and
H. Stankovicova, Farmaco, 1998, 53, 224–232.
26 H. Okazaki, T. Kishi, T. Beppu and K. Arima, J. Antibiot.,
1975, 28, 717–719.
27 Y. L. Li, H. Chen, Z. S. Zeng, X. S. Wang, D. Q. Shi and S. J. Tu,
Chin. J. Org. Chem., 2005, 25, 846–849.
28 X. S. Wang, D. Q. Shi, Y. L. Li, H. Chen, X. Y. Wei and
Z. M. Zong, Synth. Commun., 2005, 35, 97–104.
29 P. Zhang, Y. D. Yu and Z. H. Zhang, Synth. Commun., 2008,
38, 4474–4479.
30 L. Nagarapu, S. Karnakanti, R. Bantu and B. Sridhar, Synth.
Commun., 2012, 42(7), 967–974.
31 J. Sheng, M. M. Zhang, H. Jiang and X. S. Wang, J. Chin.
Chem. Soc., 2012, 59, 650–654.
32 (a) S. Kobayashi, Chem. Lett., 1991, 2187; (b) H. Firouzabadi,
N. Iranpoor and A. Garzan, Adv. Synth. Catal., 2005, 347,
1925–1928.
8 R. S. Makkar and K. J. Rockne, Environ. Toxicol. Chem., 2003,
22, 2280–2292.
9 (a) J. Desai and I. Banat, Microbiol. Mol. Biol. Rev., 1997, 61,
47–64; (b) A. Fiechter, Trends Biotechnol., 1992, 10, 208–217;
(c) W. Finnerty, Curr. Opin. Biotechnol., 1994, 5, 291–295;
(d) S. Lin, J. Chem. Technol. Biotechnol., 1996, 66, 109–120;
(e) S. Cameotra and R. Makkar, Appl. Microbiol. Biotechnol.,
1998, 50, 520–529.
10 (a) R. Makkar and S. Cameotra, Appl. Microbiol. Biotechnol.,
2002, 58, 428–434; (b) S. Itoh, Fat Sci. Technol., 1987, 89,
470–472; (c) M. Brown, Int. J. Cosmet. Sci., 1991, 13, 61–64.
11 A. Bocco, M. E. Cuvelier, H. Richard and C. Berset, J. Agric.
Food Chem., 1998, 46(6), 2123–2129.
´
33 (a) M. Bustamante, N. Duran and M. C. Diez, J. Soil Sci. Plant
12 R. Hardman, Environ. Health Perspect., 2006, 114, 165–172.
13 (a) N. Lewinski, V. Colvin and R. Drezek, Small, 2008, 4, 26–
Nutr., 2012, 12(4), 667–687; (b) R. D. Chakravarthy,
V. Ramkumar and D. K. Chand, Green Chem., 2014, 16,
2190–2196.
´
´
´
49; (b) J. C. Espın, M. T. Garcıa-Conesa and F. A. Tomas-
´
Barberan, Phytochemistry, 2007, 68, 2986–3008.
14 J. L. Limer, and V. Speirs, Breast Cancer Res., 2004, 6, 119–
127.
84620 | RSC Adv., 2015, 5, 84610–84620
This journal is © The Royal Society of Chemistry 2015