Chickpea leaf exudates: A green Br?nsted acid type biosurfactant for bis(indole)methane and bis(pyrazolyl)methane synthesis

Article abstract of DOI:10.1039/d1nj00382h

A clean and highly efficient protocol for green synthesis of bis(indole)methanes and bis(pyrazolyl)methanes has been successfully achieved by using a naturally sourced bio-surfactant, chickpea leaf exudates (CLE), as a Br?nsted acid-type catalyst. The rea

Full text of DOI:10.1039/d1nj00382h

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Chickpea leaf exudates: a green Brønsted acid
type biosurfactant for bis(indole)methane and
bis(pyrazolyl)methane synthesis†
Cite this: DOI: 10.1039/d1nj00382h
a
a
b
Rupesh C. Patil,
Suresh S. Patil
Shashikant A. Damate, Dnyandev N. Zambare and
a
*
A
clean and highly efficient protocol for green synthesis of bis(indole)methanes and
bis(pyrazolyl)methanes has been successfully achieved by using a naturally sourced bio-surfactant,
chickpea leaf exudates (CLE), as a Brønsted acid-type catalyst. The reaction proceeds smoothly with CLE
in alcoholic medium at 60 1C in a very short reaction time, and therefore it is a green, environmentally
sound alternative to the existing protocols. In comparison to the reported conventional methods, this
synthetic pathway complies with several key requirements of green chemistry principles such as
avoiding the use of any toxic/hazardous catalyst and additives/promoters, the use of a biodegradable
catalyst obtained from renewable resources, auxiliary solvent conditions, and reusability of the catalyst.
Thus, the reported protocol offers an attractive option because of its ecological safety, straightforward
work-up procedure and excellent values of green chemistry metrics as compared with other reported
methods.
Received 24th January 2021,
Accepted 11th April 2021
DOI: 10.1039/d1nj00382h
rsc.li/njc
6
criteria. Furthermore, the environmental risks posed by volatile
and toxic organic solvents have become a major concern, as
1
. Introduction
C–C bonding in organic transformations is an indispensable organic reactions employ more consumption of solvents than
7
tool for synthesis of numerous structural moieties which are reactants and the employed solvents are difficult to recycle; to
indeed building blocks of agrochemicals, natural products, overcome this problem, the first task is to replace organic
1
,2
medicinally important compounds, and so forth. The simplest solvents with auxiliary ones.
and of course the most imperative synthetic transformations are
Nowadays, an important aspect which is receiving growing
based on formation of carbon–carbon and carbon–nitrogen attention is the use of alternative reaction media that avoid the
bonds. These transformations have been proved as a pioneer problems associated with many of the traditional volatile
8
for synthesis of various biologically active compounds and organic solvents. The use of hazardous solvents in the
construction of fine chemicals pharmaceutical agents, and smart chemical industry is associated with a variety of indirect
engineering materials, including conducting polymers and environmental impacts such as non-renewable resource
3
–5
molecular wires.
reduction as a result of petrochemical solvent production, air
Due to the environmental issues associated with many emissions due to solvent incineration or high energy investment
9
organic transformations, there is a huge challenge for researchers for solvent recycling processes. Therefore, the ability to
to develop chemical processes using more environmentally efficiently carry out organic reactions in more environmentally
acceptable reagents, catalysts, solvents, and atom-efficient friendly solvents remains an important object of green chemistry
methods, and energy-efficient technologies eliminating waste research. It means that, wherever practicable, synthetic methods
production as well as employing renewable feedstocks are should be designed to use and generate substances that possess
experiencing a profound challenge to meet sustainability little or no toxicity to animal as well as human health and the
1
0
environment. Our interest is using easily available natural
feedstocks to replace chemical catalysts and solvents.
a
Synthetic Research Laboratory, PG Department of Chemistry, PDVP College,
affiliated to Shivaji University, Kolhapur), Tasgaon, Sangli (MS), 416312, India.
(
Biosurfactants, being naturally sourced materials, have certain
advantages over chemical surfactants, such as their biodegradable
nature, their less toxic nature, and their ecological acceptability.
One of the fundamental properties of surfactants is their self-
association into organized molecular structures such as micelles,
E-mail: sanyujapatil@yahoo.com
b
Department of Chemistry, Kisan Veer Mahavidyalaya, (affiliated to Shivaji
University, Kolhapur) Wai, Satara (MS), 412803, India
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
d1nj00382h
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vesicles, microemulsions, bilayers, membranes and liquid also extensively applied as fungicides, pesticides, insecticides and
11
41
crystals. The simplest class of association colloids is the micelle. dyestuffs. Bis(pyrazolyl)methanes are usually synthesized by the
The micellisation characteristics of surfactants are determined by reaction of aryl aldehydes with hydrazine hydrate and ethyl
micellization parameters such as the critical micelle concentration, acetoacetate. For this purpose, a variety of methodologies with
42
43
aggregation number, etc. Combined Brønsted acid surfactant different catalysts including microwave irradiation, electrolysis,
1
2
44
45
catalysts have also been employed in several organic reactions.
ultrasound irradiation, the solvent free approach, under
46
47
48
Considering the significance of surfactants, in this work, chickpea aqueous conditions, using ionic liquids, use of acids, use of
4
9
50
leaf exudates (CLE) were chosen as catalytic media without using nano-materials, and in micellar media have been reported.
any external promoters, external acids, ligands, biphasic media These reported methods have their own limitations such as low
and ionic liquids. The catalytic medium is directly collected yield, lower product selectivity and an environmentally toxic
from the chickpea leaf. From the literature record, the botanical catalyst. Considering these aspects, new methodologies in mild
name of chickpea is Cicer arietinum, locally known as chana (or reaction conditions with a cheap and easily available catalyst will
harbhara) in India; commonly cultivated on a farm, it is an be beneficial as an interesting challenge. Although diverse
important source of protein for the local population. Chickpea is approaches towards the synthesis of these derivatives have been
a grain legume adapted to dry and cool environments in Central developed, the use of a bio-surfactant is the most elegant strategy.
and South America, southern Europe, western and southern Asia,
Therefore, the aim of the present work is to explore the
and eastern and northern Africa. A solution containing surfactants synthetic utility of a naturally sourced acidic bio-surfactant in
shows appreciable changes in the physical and chemical carbon–carbon and carbon–nitrogen bond formation.
properties at the critical micelle concentration (CMC). The CMC Considering the significance of a naturally sourced catalytic
is the concentration of surfactants above which micelles form medium, we explore the catalytic activity of CLE for the
spontaneously. Efficient surfactants have very low CMC values, i.e. synthesis of bis(indole)methanes (Scheme 1) starting from
13,14
less surfactant is required to decrease the surface tension.
readily available substituted indole and aryl aldehydes and
Nowadays, the development of bis(indolyl)methanes has also synthesis of bis(pyrazolyl)methanes starting from aryl
received significant attention because they are present in a aldehyde, ethyl acetoacetate, and hydrazine hydrate in iso-
variety of natural products and also play a vital role in plant propanol. To the best of our knowledge based on a literature
1
5
growth, biomedicine, and agriculture. In addition, these survey, the pronounced catalytic effect of CLE as a Brønsted
heterocyclic compounds and their analogues present various natural acid type biosurfactant is being described for the first
important biological and many pharmacological activities, time for organic synthesis and the CMC was determined by the
1
6
17
18
such as antitumor, antileishmanial, antihyperlipidemic,
conductivity method.
1
9
anticancer, antifungal, anti-inflammatory, antibacterial, anti-
biotic, and analgesic properties. Some applied methodologies
with different catalysts such as microwave irradiation, visible
20
21
2
. Experimental section
22
23
24
light,
infrared,
the grinding technique,
ultrasound irradiation,
25
26
2.1 General information
the solvent free approach,
under aqueous
27
28
29
conditions, using an ionic liquid, use of acids, use of nano- Except chickpea leaf exudates all reactants and solvents were
materials, use of natural materials, in micellar media, and commercially obtained from Sigma-Aldrich and used without
eco-friendly reagents and catalysts have been reported.
The 4,4 -(arylmethylene)bis(1H-pyrazol-5-ols) are another ATR technique on a Bruker ALPHA FT-IR spectrometer.
important class of bis-heterocyclic compounds. This is because Thermal gravimetric analysis (TGA) was performed using a TA
the pyrazolone nucleus is one of the most important nitrogen SDT Q600 V20.9 Build 20 instrument in nitrogen at a linear
30
31
32
33
further purification. The FTIR spectra were recorded using the
0
ꢀ1
1
heterocyclic moieties found in numerous bioactive molecules heating rate of 10 1C min . The H NMR spectra (300 MHz and
3
4
13
with predominant properties such as cytokine inhibitory,
400 MHz) and C NMR spectra (75.5 MHz and 100 MHz) were
3
5
36
COX-2 inhibitory, and antitumor properties. 2,4-Dihydro- measured with AVANCE-300 instruments, using TMS as an
0
3
H-pyrazol-3-one derivatives including 4,4 -(arylmethylene) internal standard in DMSO-d6 and CDCl3 as a solvent.
bis(1H-pyrazol-5-ols) also display a wide range of pharmacological The pH of the catalyst and aqueous solutions of chemical
37
38
activities for use as antibacterial, antidepressant, and antima- surfactants was measured using a digital pH meter (model
39
40
larial agents, and a gastric secretion stimulatory drug. They are EQ-610). An HPLC-MS instrument (6200 series TOF/6500 series
Scheme 1 Synthesis of bis(indole)methane derivatives.
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Q-TOF B.05.01 (B5125.3); Agilent Technologies, Santa Clara, CA, washing with 5.0 mL cold water. The pure products were
USA) was used for determination of the organic components in obtained by recrystallization with 96% ethanol. All the products
the CLE catalyst. Thin layer chromatography (TLC) analysis was were confirmed by the spectroscopic method using NMR and
performed on silica gel 60-F254 pre coated plates (250 mm FT-IR. The physical and spectroscopic data are consistent with
layers). Optical microscopy measurements:
a
drop of the proposed structure and is in harmony with the literature
turbid reaction mixture was subjected to light microscopy mea- values.
surements using an ordinary light microscope under 50ꢁ and
2
.4 General procedure for the synthesis of 4-((5-hydroxy-3-
1
00ꢁ magnification. The conductivity measurements for the
methyl-1H-pyrazol-4-yl)(4-methoxyphenyl)methyl)-3-methyl-1H-
pyrazol-5-ol
CMC were performed with an Equiptronics (Model EQ-660B) digital
ꢀ
1
auto ranging conductometer with a cell constant = 1 cm
.
In a 25 mL round bottom flask aryl aldehyde (1.0 mmol), ethyl
acetoacetate (2.0 mmol), and hydrazine hydrate (2.0 mmol)
2.2 Collection of chickpea leaf exudates
For quantitative collection of CLE as a catalytic medium we were placed in a solution of CLE (5.0 mL) in iso-PrOH (3.0 mL)
consider the growing period of newly cultivated chickpea crops. and stirred at 60 1C in a preheated oil bath till the completion of
At first, for the purpose of exudate collection, cultivated crops on the reaction as indicated by TLC (petroleum : ethyl acetate). After
various lands were selected and then exudates were collected completion of the reaction, 5.0 mL water was added to the
manually using a clean and soft cotton cloth by an absorption– reaction mixture. The solid products were separated by simple
wringing process. It was observed that a good quantity of filtration followed by washing with 5.0 mL cold water. The pure
exudates was obtained from chickpea crops of two months old products were obtained by recrystallization with 96% ethanol.
(
just before the flowering stage). It was also observed that the Representative compounds were confirmed by physical
early morning (5.00 am to 6.00 am) period gave good collection constants and characterized by spectral analysis.
of exudates (ESI†). The pH of the collected exudates was
measured using a pH-meter before use and it was found to be
3
. Results and discussion
1.1. The collected catalyst was stored for several days at 5 1C.
3
.1 Characterization of the catalyst
.1.1 HPLC-MS studies. High performance liquid
chromatography-mass spectroscopy (HPLC-MS) is an analytical
2.3 General procedure for the synthesis of 3-((1H-indol-3-yl)
3
(
4-methoxyphenyl)methyl)-1H-indol
All the reactions were carried out under an air atmosphere in technique commonly used to identify the presence of organic
pre-dried glassware. A mixture of indoles (2.0 mmol), and aryl components in biological samples. It has been reported that
aldehydes (1.0 mmol) in a solution of CLE (5.0 mL) and the leaf surfaces of the chickpea plant secrete several organic
5
1,52
iso-PrOH (3.0 mL) was stirred at 60 1C in a preheated oil bath acids
till the completion of the reaction as indicated by TLC (petro- which are responsible for the highly acidic nature (1.1 pH) and
such as malic, succinic, oxalic, quinic and citric acids
5
3
leum ether : ethyl acetate). After completion of the reaction, have been correlated with reduced pod damage. Because of
.0 mL water was added to the reaction mixture. The solid the acidic nature of CLE due to the presence of different
products were separated by simple filtration followed by organic acids reported in the literature, we decided to
5
5
4
Fig. 1 Structures of acids present in CLE.
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a
Table 1 Optimization of the reaction conditions for the model reaction
CLE
Entry (mL)
Co-surfactant (3
mL)
Temp.
(1C)
Time
(min)
b
Yield (%)
1
2
3
4
5
6
7
8
9
10
0.5
1.0
1.5
2.0
2.5
3.0
4.0
5.0
3.0
3.0
3.0
3.0
3.0
1.0
2.0
5.0
7.0
9.0
5.0
—
—
—
—
—
—
—
—
—
Rt
Rt
Rt
Rt
Rt
Rt
Rt
Rt
60
60
60
60
60
60
60
60
60
60
Rt
60
180
180
180
180
180
180
180
180
60
30
30
60
60
60
60
30
60
60
60
60
Trace
Trace
Trace
12
15
32
32
32
c
Fig. 2 FTIR spectra of (a) the CLE catalyst, (b) neat pyridine and (c) a
mixture of pyridine with the CLE catalyst.
—
69 (70, 69)
MeOH
EtOH
iso-PrOH
t-BuOH
iso-PrOH
iso-PrOH
iso-PrOH
iso-PrOH
iso-PrOH
iso-PrOH
iso-PrOH
81
88
94
82
84
88
96
90
82
36
Nr
1
1
1
1
1
1
2
3
4
5
investigate the presence of these acids in the exudates. For this
investigation we analyzed a fresh CLE sample by HPLC-MS and
more than 50 acids along with other organic components were 16
1
1
1
7
8
9
detected as shown in Fig. 1. The mass spectra of all acids are
given in the ESI.†
In view of these data and in continuation of our ongoing 20
research in the development of green synthetic protocols
a
Reaction conditions: 4-methoxybenzaldehyde (1.0 mmol), indole
5
5,56
b
c
utilizing natural feedstocks,
we thought that this amazing (2.0 mmol) and CLE (mL). Isolated yield. Temperature: 80 1C, 90 1C.
medium may serve as a Brønsted acid type biosurfactant for
this transformation.
ꢀ
1
(
Fig. 2c). Also the band observed at 1637 cm indicates the
3
.1.2 FTIR analysis. The FTIR spectra of CLE were recorded
ꢀ
1
ꢀ
1
presence of –CQC– bonds and that at 1390 cm indicates –OH
bending vibrations present.
in a frequency range 1850–1300 cm using pyridine as a probe
for Brønsted acidity measurement. The presence of a band near
582 cm is an indication of the formation of pyridinium ions
ꢀ
1
3.1.3. TGA analysis. As indicated in Fig. 3, the thermal
stability of CLE was determined by thermogravimetric analysis.
The TGA curves of CLE show three thermal decomposition
peaks. The initial weight loss of 36.29% below 55.98 1C is
due to the most volatile component present in CLE. The major
weight loss of 51.30% up to 110 1C is attributed to dehydroxy-
lation and decarboxylation of water soluble acids. The third
weight loss of 2.664% corresponds to the decomposition of
organic compounds. The DSC-TGA data confirm that the catalyst
is stable to 120 1C.
1
resulting from the presence of Brønsted acid sites. In this work
CLE (Fig. 2a), neat pyridine (Fig. 2b) and pyridine added to CLE
(
Fig. 2c) show well resolved spectra. The observation of an
ꢀ
1
absorption band at 1587 cm
due to the formation of
pyridinium ions suggests that Brønsted acids are also present
Fig. 4 The phenomenon of the reaction between 4-methoxybenzaldehyde
and indole: (a) homogeneous phase of the reactants and catalyst at the
beginning of the reaction, (b) the reaction mixture after 5 min, and (c) product
formation after reaction completion.
Fig. 3 DSC-TGA curves of CLE.
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3.2.1 Optimization of the reaction conditions. For optimi-
zation of the reaction conditions, a 25 mL round bottom flask
was charged with 4-methoxybenzaldehyde (1.0 mmol), and
indole (2.0 mmol) as a model substrate in the presence of
CLE, and the reaction mixture was stirred at room temperature.
After 3 h a low yield (32%) of corresponding product 3a was
observed in TLC (Table 1, entry 6). On increasing or decreasing
the catalytic amount (0.5 to 5 mL), no significant improvement
in the results was obtained after a prolonged reaction time
Fig. 5 Optical microscopic images of the model reaction mixture –
normal view and magnified view.
(Table 1, entries 1 to 8). We continued our efforts for improvement
of the results and when the model reactants were allowed to react
under elevated temperature conditions in the presence of 3 mL
CLE, surprisingly at a 60 1C temperature the product yields were
doubled, while on a further increase in temperature nearly the
same results were recorded (Table 1, entry 9) after 3 h. However,
we were not satisfied with these moderate results and, since
solvents play a crucial role in organic synthesis, the effect of
solvents as co-surfactants was studied for the model reaction
(Table 1, entries 10–13). Among the tested co-surfactants, it was
found that iso-propanol was found to be more efficient for the
present transformation (Table 1, entry 12).
The amounts and nature of the organic solvent have
produced a significant change in the properties of surfactants.
Iso-propanol provides dual performance (co-surfactant and
5
7
co-solvent) for organic transformation. Iso-propanol as a co-
surfactant increases the hydrophobicity of the micellar medium
of the catalyst while as a co-solvent it increases the solubility of
the reactants in the reaction mixture. Therefore, iso-propanol at
a 60 1C temperature efficiently worked as a co-surfactant leading
to effective synthesis of 3a along with enhanced product yield. It
Fig. 6 Plot of specific conductance against percentage composition of CLE.
3.2 Application of CLE for bis(indole)methane and
bis(pyrazolyl)methane synthesis
Our initial studies were focused on the development of an was also noticed that the condensation using a co-surfactant
optimum set of reaction conditions for the synthesis of proceeded rapidly and was superior to the reported procedures
5
8,59
bis(indole)methane using chickpea leaf exudates as a bio-based with respect to the reaction time and yields of the product.
catalyst by reacting aryl aldehyde and substituted indoles in
alcoholic conditions.
Furthermore, we also optimized the surfactant : co-surfactant
ratio for the model reaction by changing the amount of CLE
Fig. 7 Mechanistic picture of the role of micelles for bis(indole)methane formation.
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a
Table 2 CLE-catalyzed synthesis of bis(indole)methane derivatives (3a–t)
a
b
c
Reaction conditions: aryl aldehydes (1.0 mmol), substituted indole (2.0 mmol), CLE (5.0 mL), and iso-PrOH (3mL) at 60 1C. Entry. Time
d
in min. Isolated yields in %.
(Table 1, entries 14–18). The results showed that a surfactant : co- conditions, a 36% yield of 3a was obtained (Table 1, entry 19).
surfactant ratio at just above the CMC (30%) is a suitable reaction Moreover, the catalyst-free condition was also examined (Table 1,
medium for smooth conversion of the reactant to the product entry 20); the result observed was a viscous reaction system with
with respect to time and yield (Table 1, entry 16). From these no product formation, which indicates that the role of the bio-
results, it was also revealed that further decreasing or increasing surfactant is decisive for bis(indole)methane formation.
the surfactant : co-surfactant proportion reduces the yield of the
The HPLC-MS study of CLE showed the presence of several
desired product. At ambient temperature with the same reaction organic acids along with other organic components, which may
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Table 3 Comparison of the efficiency of different chemical surfactants with the CLE bio-surfactant for synthesis of 3a
Entry
Surfactants
Time
Yield (%)
Ref.
1
2
3
4
5
6
7
8
9
Sodium dodecyl sulfate (SDS)
Dodecylsulphonic acid (DSA)
Tetrabutylammonium tribromide (TBATB)
Tetrabutylammonium tribromide (TBAT)
Sodium 4-dodecylbenzenesulfonic acid (SDBS)
Cetyltrimethylammonium bromide (CTAB)
Ferric dodecyl sulfonate [Fe(DS)
Ytterbium(III) triflate/sodium dodecyl sulfate (Yb(OTf)
Chickpea leaf exudates (CLE)
5 h
80
94
95
65
70
20
80
84
96
60
61
62
63
64
64
65
66
18 min
30 min
3 h
4.5 h
5 h
8 h
1.5 h
30 min
3
]
3
/SDS)
Present work
0
Scheme 2 Synthesis of 4,4 -(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols).
interactions will cause binding of these compounds to the
micelles and they will get collected in the core of the micelle
where the reaction occurs more easily. This further confirmed
that the catalyst does not simply provide the acidic medium to
activate the substrate molecules but also helps to aggregate all
the reactants into micelles.
3.2.2 Determination of the CMC by the conductivity
method. To maintain a proper CLE : iso-PrOH composition for
this condensation reaction, we employed electrical conductivity
measurement experiments to determine the CMC and it was
found to be 30% v/v (Fig. 6).
Fig. 8 The phenomenon of the reaction between 4-methoxybenzaldehydes
1.0 mmol), hydrazinehydrates (2.0 mmol), and ethyl acetoacetate (2.0 mmol):
a) the homogeneous phase of the reactants and catalyst at the beginning of
During organic transformations micelle formation occurs
above the CMC, at which the reactants undergo self-assembly to
form aggregates in the solution, which causes conversion of the
true solution to a colloidal system. The micellar solution is
known as a colloidal dispersion of organized surfactant
molecules. The micelle formed in the solution is in a spherical
(
(
the reaction, (b) the reaction mixture after 5 min, and (c) product formation
after reaction completion.
collectively form micelles in the reaction mixture and support form in which the hydrophobic tails face toward the interior of
moving the reactions in the proper direction. We thought that the micelle structure while the hydrophilic head group is
this amazing medium may serve as an acidic bio-surfactant, a exposed to the solution. The role of micelles to catalyze the
better alternative to chemical surfactants and also to harmful reaction in this condensation is schematically represented in
corrosive acids used for organic transformations.
Fig. 7.
After optimization of the reaction conditions, condensation
At the beginning, the clear reaction mixture turned to a
turbid emulsion (Fig. 4), which implies that there is the reactions were carried out in CLE : iso-PrOH (5 : 3, v/v) at 60 1C
formation of micelles or micelle-like colloidal aggregates, using a series of structurally diverse aryl aldehydes with sub-
which was visualized through an optical microscope (Fig. 5).
The aggregation of organic ingredients from CLE under the (–NO , –Cl, –Br) as well as electron-donating (–OCH , –OH,
stituted indoles. Aldehydes with electron-withdrawing groups
2
3
reaction conditions results in the semi-ordered structure of –N(CH ) ) and hetero aromatic functionalities reacted
3
2
micelles protruding into the aqueous phase, whereas the successfully and gave the expected products in the stipulated
hydrophobic parts are brought into close proximity in the core time period (Table 2).
of the aggregate excluding water. When organic compounds are
Thus, the acidic nature of the exudates and the surfactant
introduced in an alcoholic micellar solution, hydrophobic activity due to different organic acids offered a synergistic
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a
Table 4 CLE-catalyzed synthesis of 4,4 -(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ol) derivatives (7a–n)
a
Reaction conditions: aryl aldehydes (1.0 mmol), hydrazinehydrates (2.0 mmol), ethyl acetoacetate (2.0 mmol), CLE (5.0 mL), and iso-PrOH
b
c
d
(3.0 mL), 60 1C. Entry. Time in min. Isolated yields in %.
Table 5 Comparison of the efficiency of different chemical surfactants with the CLE bio-surfactant for synthesis of 7a
Entry
Surfactants
Time
Yield (%)
Ref.
1
6
Sodium dodecyl sulfate (SDS)
Sodium dodecyl benzene sulfonate (SDBS)
Chickpea leaf exudates (CLE)
5 h
4.5 h
15 min
80
70
94
60
67
1
0
Present work
effect, and the reaction proceeded rapidly in a short time. The
At the beginning, the yellow colour reaction mixture turned
comparison of efficiency of the different chemical surfactants to a turbid emulsion (Fig. 8), which implies that there is the
with CLE bio-surfactant has been presented (Table 3, entries formation of micelles or micelle-like colloidal aggregates, and
1–8). The surfactant obtained from chickpea leaf was found to the obtained product was separated easily with the procedure
be excellent with respect to time as well as the yield of the described in the experimental procedure.
product (Table 3, entry 9), suggesting that both the surfactant
Condensation reactions were carried out in 5.0 mL CLE and
property and strong Brønsted acidity of CLE are essential to iso-propanol at 60 1C using a series of structurally diverse aryl
promote the reaction efficiency.
aldehydes with hydrazine hydrate and ethyl acetoacetate
Inspired by these tempting results obtained for condensation (Table 4). As the data in this table show, CLE were simple
of aldehydes with indoles to afford the desired bis(indole) and highly efficient for the reaction; all aryl aldehydes (containing
methanes, we extended the optimized protocol for a one-pot electron-donating substituents, electron-withdrawing substituents
0
pseudo five component synthesis of 4,4 -(arylmethylene)bis(3- and halogens) afforded the desired products in high yields within
methyl-1-phenyl-1H-pyrazol-5-ols) (Scheme 2).
short reaction times.
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Acknowledgements
One of the authors, Rupesh C. Patil is grateful to Chhatrapati
Shahu Maharaj Research Training and Human Development
Institute (SARTHI), Pune (Government of Maharashtra), India
for the award of the CMSRF-2019 fellowship. [CIN-U74999PN-
2018NPL177394, dated 11th Sept. 2019].
References
1
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7
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4
. Conclusion
In conclusion, we report a simple and new approach for
synthesis of bis(indole)methanes and bis(pyrazolyl)methanes
which represents a highly efficient and environmentally benign
protocol. Apart from this, simplicity of product separation and
effortless reusability of the catalyst are the significant
advantages of this protocol. This new natural Brønsted acid
bio-surfactant should thereby provide an attractive alternative
to harmful corrosive catalysts. However in a true sense we think
that a bio-surfactant doesn’t offer only a synergistic effect of
acidic nature and surfactant activity but there might be a
combination of many other factors. Hence to have a good
contribution in innovation of green chemistry, we will lengthen
our research to have more exposure to natural surfactant
catalyzed organic transformations.
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7 S. B. Bharate, J. B. Bharate, S. I. Khan, B. L. Tekwani,
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There are no conflicts to declare.
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