Ash of pomegranate peels (APP): A bio-waste heterogeneous catalyst for sustainable synthesis of α,α′-bis(substituted benzylidine)cycloalkanones and 2-arylidene-1-tetralones

Article abstract of DOI:10.1007/s11164-020-04160-5

Abstract: α,α′-bis(substituted benzylidene)cycloalkanones were efficiently prepared from variously substituted aldehydes and cycloalkanones in water by using ash of pomegranate peels (APP) as a catalyst. The APP-catalyst was obtained from bio-waste by simple thermal treatment to dry peels of pomegranate fruit and formation of its active phase was confirmed by FT-IR, XRD, XRF, EDX, SEM, DSC-TGA and BET techniques. The analysis revealed that the present catalyst has basic sites which promote the synthesis of desired products. The main attractions of our protocol are utilization of highly abundant bio-waste-derived catalyst and good-to-excellent yield in shortest reaction time. This green protocol was further extended for structurally diverse 2-arylidene-1-tetralones by condensation of equimolar quantity of aromatic aldehydes and 1-tetralone at low temperature. The catalyst could be quantitatively recovered and reused effectively for five times. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-020-04160-5

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-020-04160-5
Ash of pomegranate peels (APP): A bio‑waste
heterogeneous catalyst for sustainable synthesis
of α,α′‑bis(substituted benzylidine)cycloalkanones
and 2‑arylidene‑1‑tetralones
Rupesh C. Patil1 · Uttam P. Patil2 · Ashutosh A. Jagdale1 ·
Sachinkumar K. Shinde1 · Suresh S. Patil1
Received: 13 January 2020 / Accepted: 15 April 2020
© Springer Nature B.V. 2020
Abstract
α,α′-bis(substituted benzylidene)cycloalkanones were efciently prepared from
variously substituted aldehydes and cycloalkanones in water by using ash of pome-
granate peels (APP) as a catalyst. The APP-catalyst was obtained from bio-waste
by simple thermal treatment to dry peels of pomegranate fruit and formation of its
active phase was confrmed by FT-IR, XRD, XRF, EDX, SEM, DSC-TGA and BET
techniques. The analysis revealed that the present catalyst has basic sites which pro-
mote the synthesis of desired products. The main attractions of our protocol are uti-
lization of highly abundant bio-waste-derived catalyst and good-to-excellent yield
in shortest reaction time. This green protocol was further extended for structurally
diverse 2-arylidene-1-tetralones by condensation of equimolar quantity of aromatic
aldehydes and 1-tetralone at low temperature. The catalyst could be quantitatively
recovered and reused efectively for fve times.
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1116
4-020-04160-5) contains supplementary material, which is available to authorized users.
* Suresh S. Patil
sanyujapatil@yahoo.com
1
Synthetic Research Laboratory, PG Department of Chemistry, PDVP College (Dist. Sangli,
afliated to Shivaji University, Kolhapur-416004, Maharashtra, India), Tasgaon 416312, India
2
Department of Chemistry, ACS College (Dist. Sangli, Afliated to Shivaji University,
Kolhapur-416004, Maharashtra, India), Palus 416310, India
Vol.:(0123456789)
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R. C. Patil et al.
Graphic abstract
Keywords α,α′-Bis(substituted benzylidene)cycloalkanones · 2-Arylidene-1-
tetralones · Bio-waste · Pomegranate peels · Natural catalyst
Introduction
In the modern era of synthetic chemistry, the synthesis of complex and diverse
molecular architectures from simple and easily available starting materials while
simultaneously meeting environmental and economic concerns is important from
both industrial and academic points of view [1]. The development of proactive path
for organic transformations with high efcacy and reduced environmental impact
is an important goal in green chemistry and future sciences. While considering
increasing environmental pollution and its intensive impact on living systems, the
development of chemical processes using more environment-friendly chemicals,
atom-efcient methods and energy-saving technologies eliminating waste produc-
tion is the urgent requirement [2]. Furthermore, owing to typical reactivity and
selectivity, reactions are preferred in green solvents like water because it is easily
available, non-toxic and non-fammable solvent. Reactions in aqueous medium not
only possess negative activation volume but also help in controlling exothermic
reactions. Hence, organic transformations under aqueous conditions are preferred
from both environmental and economical point of view [3].
Bis-benzylidene cycloalkanone derivatives fnd a broad range of applications
in the feld of biology, medicinal chemistry and pharmacology. This structural
motif is broadly represented by several types of natural products, manifest-
ing diverse biological and pharmacological activities including pharmaceuti-
cal [4], agrochemical and perfume intermediates [5] as well as synthesis of liq-
uid crystal polymers [6], also these are very important precursors to potentially
bioactive pyrimidine derivatives [7], quinine reductase inducer derivatives [8],
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Ash of pomegranate peels (APP): A bio-waste heterogeneous…
cholesterol-lowering agents [9], antiparasitic agents [10], bis-spiropyrrolidines
[11], cytotoxicity [12] histone acetyl transferase inhibitory activities [13] and
many others.
On the account of widespread applicability of bis-benzylidene cycloalkanone
derivatives, considerable attention has been focused on the development of clean,
efcient and environment-friendly methodologies to synthesize these scafolds
via one-pot three-component reactions. The literature report revealed that very
limited methodologies have been reported for the synthesis of bis-benzylidene
cycloalkanone such as microwave [14], ultra-sound irradiation [15], basic catalyst
[16], ionic liquids [17], micellar media [18], nano-materials [19], organometallic
complexes [20] and polymer-supported catalyst [21]. Each of these methods has
its own merit, but some of them sufer from demerits such as use of organic sol-
vents, hazardous reagents, time-consuming processes, sometimes non-reproduci-
ble base catalysts and complications for the separation of homogeneous catalysts
from the reaction mixture are the problems associated with these methods.
At present, synthetic processes involving bio-waste-derived catalysts are
receiving much attention as a viable alternative for the development of green
methodologies in organic transformations [22–24]. Bio-wastes are a better choice
in certain conditions because of number of characteristics such as they are cheap-
est, obtained from renewable resources, a very simple procedure is followed in
the preparation, the strategy involved also provides a high yield and good recy-
clability of the catalyst. Therefore, the objective of the present work is to explore
the synthetic utility of bio-waste as a natural catalyst in organic transformations.
Interestingly, in recent years, various types of agro-waste biomass have been
used as catalysts for numerous organic transformations [25, 26]. Nevertheless, to
the best of our knowledge, there are no any reports in the literature where the
agro biomass is exploited as a catalyst for cross-aldol condensation reaction. In
continuation of our research program concerning the development of naturally
sourced catalysts [27–30], we are going to utilize bio-waste pomegranate fruit
peels after thermal treatment as an efcient catalyst for cross-aldol condensation.
Herein, we report for the frst time, a simple and environmentally benign route for
the exclusive synthesis of a, a’-bis(substituted benzylidene)cycloalkanones via a
cross-aldol condensation reaction (Scheme 1) using APP-catalyst as a heteroge-
neous solid catalyst in aqueous medium without addition of any external base.
Scheme 1 Synthesis of a, a’-bis(substituted benzylidene)cycloalkanones using APP-catalyst
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R. C. Patil et al.
Experimental procedure
Materials and methods
Except pomegranate fruit peels, all chemicals used in the study were purchased
from Sigma-Aldrich and used without additional drying and purifcation. The forma-
tion of products was checked by TLC on precoated Merck silica gel 60 F254 alu-
minum sheets. IR spectrum was recorded in ATR technique on a Bruker ALPHA
FT-IR spectrometer. XRD measurements were carried out on a Bruker AXS ana-
lytical instrument Pvt. Ltd. Germany, Model: D2 phaser with Cu Kα radiation
(λ=1.54060Aº) at 40 mA, 45 kV a scan step time 10.3366 s, a start position 10.0184
and end position 99.9824 [2ºTh]. SEM images were obtained on FEI, NOVA,
NanoSem 450 equipment. Quanta 200 3D, FEI scanning electron microscope used
for energy-dispersive X-ray spectroscopy (EDX) analysis. N2-adsorption–desorp-
tion isotherms were obtained with a BELSORP surface area and porosity analyzer.
XRF analysis of APP-catalyst was performed on X-ray fuorescence spectrometer
(Pananlytical, USA). The thermal gravimetric analysis (TGA) was obtained using
a TA SDT Q600 V20.9 Build 20 instrument in the presence of air at a linear heat-
ing rate of 10 °C min−1. Proton and carbon-13 NMR spectra were measured with
Avance-300 instrument in CDCl3 and DMSO as a solvent with TMS as an internal
standard.
Preparation of catalyst
During this study, pomegranate fruit peels (PFP) (Fig. 1a) were obtained from the
dumping waste of local food processing industry and the APP-catalyst was obtained
by thermal treatment in Mufe furnace. Initially, all attached impurities were
removed by washing several times with tap water and left in open air for two hours.
Later, they were transferred to the oven at 100 °C for drying. The dried peels (100 g)
were manually broken into small pieces then convert to peels powder (Fig. 1b),
which were treated at heating rate of 5 °C/min in mufe furnace up to 1000 °C
and this temperature was maintained for 1 h. After thermal treatment, most of the
organic materials were burnt out and got transformed into white soft ash (8.3 g). The
resulting white ash (Fig. 1c) obtained was nominated as APP and utilized for cross-
aldol condensation reaction.
Fig. 1 a Dry pomegranate fruit peels, b peel powder, c APP-catalyst
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Ash of pomegranate peels (APP): A bio-waste heterogeneous…
Typical procedure for synthesis of 2, 6‑bis(4‑methoxybenzylidene)cyclohexanone
(3j)
A mixture of 4-methoxybenzaldehyde (2 mmol) and cyclohexanone (1 mmol) in
water (3 mL) was well stirred in the presence of APP-catalyst (7 wt%) under refux
condition until completion of the reaction (30 min) monitored by TLC. After com-
pletion of the reaction, the separated solid product was obtained by simple fltration
followed by washing with distilled water (2x5 mL) and further purifed by recrystal-
lization from 96% ethanol. All other derivatives (3a–p) were synthesized by follow-
ing same protocol and confrmed by spectral techniques.
Typical procedure for synthesis of 2‑(4‑methoxybenzylidene)‑1‑tetralone (5a)
An equimolar mixture of 4-methoxybenzaldehyde (1 mmol) and 1-tetralone
(1 mmol) in water (3 mL) was magnetically stirred in the presence of APP-catalyst
(7 wt%) at 0 °C temperature until completion of the reaction (4 h) monitored by
TLC. Then, reaction mixture was kept in refrigerator overnight, the separated solid
product was obtained by simple fltration and further purifed by recrystallization
from 96% ethanol. All other derivatives (5b-j) were synthesized by following same
procedure and confrmed by spectral techniques.
Results and discussion
Catalyst Characterization
The agro-waste-derived ash catalyst was characterized by FT-IR, XRD, XRF, EDX,
SEM and BET technique.
DSC‑TGA analysis
The suitable modifcation temperature of PFP was determined by thermal gravi-
metric analysis (Fig. 2). The TGA result shows the temperatures at which the PFP
decomposed when heated in a controlled environment to avoid any misleading
oxidation reactions at a given temperature rate. The temperature ranged from 0 to
1000 °C depicting the decomposition of PFP.
Three distinct stages of weight loss were observed. In the frst step, minor
weight loss at temperatures below 103.02 °C was 6.73% occurred due to the loss of
adsorbed moisture. Another weight loss occurred in the second step between 212.98
and 410.72 °C and was 61.21%, refecting the decomposition of organic compo-
nents. In the third step, weight loss between temperature ranges of 410.72-985.76 °C
was due to the decomposition of metal carbonates. Finally, the 8.33% weight of
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R. C. Patil et al.
Fig. 2 DSC-TGA curves of parent PFP
residue remaining after the temperature of 985.76 °C was due to metal oxides and
silica.
FT‑IR analysis
The conversion of natural feedstock’s PFP into APP-catalyst was confrmed by
FT-IR analysis (Fig. 3). The observation of major absorption bands occurred at 694,
871, 1044, 1404 and 1687 cm−1 in parent PFP supports presence of metal carbonates
(K2CO3, CaCO3, MgCO3). After thermal treatment at 1000 °C, absorption bands
occurred at 606, 1022, 1509, 1687 and 1733 cm−1 clearly indicate the presence of
metal oxides (K2O, CaO, MgO).
XRD analysis
The XRD analysis of the APP-catalyst (Fig. 4) showed the characteristic peaks of
metal oxides and carbonates present in the catalyst.
The peaks at 2θ=25.81, 28.58, 31.86, 40.50 and 49.47 (JCPDS Reference No.
77-2176 and 87-0730) revealed the presence of the K2O and K2CO3, while the
intense peaks at 2θ=29.40, 30.35, 39.40, 47.44, 32.54, and 53.03 (JCPDS Reference
No. 47-1743, 37-1497) attributed to CaO and CaCO3. The peak at 2θ=42.92, and
62.31 (JCPDS Reference No. 04-0829, 75-1525) ascribed to MgO, and the peaks
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Ash of pomegranate peels (APP): A bio-waste heterogeneous…
Fig. 3 FT-IR of a parent PFP, b APP-catalyst
at 2θ=25.36, 33.05, 42.15, 50.68, 51.40 attributed to SiO2, Fe2O3, P2O5, carbon
and sulfur (JCPDS Reference No. 41-1413, 33-0664, 5-0488, 75-1621, 34-0941).
Another peak was also observed at 2θ=17.92º due to metal hydroxides. Therefore,
this active phase of the APP-catalyst was utilized for the conversion of reactant into
the desired product.
XRF analysis
X-ray fuorescence (XRF) technique is one of the simplest, analytical methods to
investigate the particular chemical composition of materials. The XRF analy-
sis revealed that the fresh APP-catalyst was found to contain K2O (25.1%), CaO
(9.83%), MgO (4.59%) as major constituents while P2O5 (3.14%), Fe2O3 (0.10%),
SiO2 (0.56%), Na2O (0.014%) as a minor constituents in the ash (ESI).
EDX analysis
The distribution of elements as based on the EDX analysis of the APP-catalyst is
shown in Fig. 5. The report reveals a very high concentration of the oxides of potas-
sium (K), calcium (Ca) and magnesium (Mg). It is believed that oxides of these ele-
ments in the presence of water produce corresponding metal hydroxides (KOH as a
1 3

R. C. Patil et al.
Counts
150
A2
100
50
0
20
30
40
50
60
70
80
90
Position [°2Theta]
Fig. 4 X-ray difraction patterns of APP-catalyst
Fig. 5 EDX spectrum of APP-catalyst
1 3

Ash of pomegranate peels (APP): A bio-waste heterogeneous…
Fig. 6 SEM images of APP-catalyst a Normal view, b Magnifed view
Fig. 7 BET isotherm and pore-size distribution curve (inset) of APP-catalyst
major constituent), which provides basic condition [31–33] to facilitate this cross-
aldol condensation.
SEM analysis
The apparent morphology of APP-catalyst examined by SEM images is shown in
Fig. 6. As observed from SEM micrographs, smaller and homogeneous particle size
may be achieved with thermal treatment to parent PFP. In general, the smaller parti-
cle size of catalyst provides large contact area for catalyzing the reaction.
1 3

R. C. Patil et al.
BET analysis
Figure 7 displays the N2 adsorption–desorption isotherms and the corresponding
pore-size distribution curve (inset) for freshly prepared APP-catalyst. The surface
area of APP-catalyst was found to be 4.54 m2 g−1 while the pore volume and pore
radius are 0.037 ccg−1 and 12.2 nm, respectively. The pore-size distribution curve
(inset) depicts mesopores of very uniform sizes. The isotherms of prepared APP-
catalyst were type III isotherm with a H4-type hysteresis loop.
Optimization of reaction conditions
At the outset of the protocol, our goal was to identify the catalytic activity of the
APP-catalyst for the synthesis of α,α′-bis(substituted benzylidene)cycloalkanones
derivatives, and we defned the following criteria: a greener solvent system, a low
catalyst loading, relatively low reaction temperature and good reaction yield in a
short reaction time. With these goals in mind, the reaction conditions were opti-
mized using 4-methoxybenzaldehyde (2 mmol) and cyclohexanone (1 mmol) as
model reactants reacting at refux condition and the observed results are sum-
marized in Table 1. At frst, the model reaction was examined under solvent-free
conditions and in the water (3 mL) without any catalyst. It was found that the
desired product, 3j was not observed on the TLC plate even after 3 h of stirring
(Table 1, entries 1, 2). As the reaction requires a catalyst, the model reaction was
performed using the APP-catalyst by varying the catalytic amounts (1–20 wt%)
in water (3 mL). It was found that when increasing the amount of the catalyst
from 1 to 5 and 7 wt% in water, the yield also increased (Table 1, entries 3, 4). A
further increase in the catalyst amount (above 10 wt%) surprisingly reduced the
yield (Table 1, entry 5), when the reaction was performed in 3 mL water. There-
fore, 7 wt% of APP-catalyst in 3 mL water is sufcient to remarkably enhance the
Table 1 Optimization of reaction condition for synthesis of 3ja
Entry
Ash catalyst (wt%)
Solvent (3 mL)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
9
–
–
–
H2O
H2O
H2O
H2O
EtOH
THF
DCM
180
180
60
30
60
30
60
60
60
Nrc
Nrc
APP (1)
APP (7)
APP (10)
APP (7)
APP (7)
APP (7)
APP (7)
APP (7)
32 (43,70)d
94
92 (89, 86)e
94
56
51
62
94
CH3CN
H2O: EtOH (1:1)
10
30
aReaction conditions: 4-methoxybenzaldehyde (2 mmol), cyclohexanone (1 mmol), catalyst (wt%)
b
c
d
e
and water (3 mL) at refux condition, isolated yield, no reaction, catalyst amount 3, 5 wt%, catalyst
amount 15, 20 wt%
1 3

Ash of pomegranate peels (APP): A bio-waste heterogeneous…
reactivity of the reactants, and the corresponding product 3j was obtained in 94%
yield within 30 min (Table 1, entry 4).
Optimization study was also performed with variation of the reaction medium.
The model reaction was examined in diferent conventional organic solvents like
EtOH, THF, DCM and CH3CN. The results reveals that THF, DCM and CH3CN
aforded low-to-moderate yields (Table 1, entries 7–9) while pure EtOH and
H2O: EtOH solvent system shows equally good performance for this conversion
(Table 1, entry 6 and 10). Thus, the best yield, cleanest reaction work-up was
achieved employing 7 wt% of APP-catalyst in water (3 mL) at room temperature.
By reacting cyclopentanone and cyclohexanone with a variety of diferently
substituted aromatic aldehydes under optimized reaction conditions, we manage
to prepared a range of α,α′-bis(substituted benzylidene)cycloalkanone derivatives.
The results are shown in Table 2. As shown, aromatic aldehydes with substitu-
ent’s carrying either electron-withdrawing or electron-donating groups reacted
successfully and gave the expected products. The reactions were completed
Table 2 APP-catalyzed synthesis of α,α’-bis(substituted benzylidene)cycloalkanones (3a–p)a
O
O
O
H3CO
OCH3
N
N
3a (25b, 96c, 188-190d [34]e)
3b (30, 98, 209-210 [34])
3c (30, 87, 270-272 [35])
O
O
O
Cl
Cl
OCH3
OCH3
O
O
O
O
Cl
Cl
OCH3
OCH3
3e (30, 87, 170-174)
3f (25,76, 260-262 [37])
3d (25, 98, 204-206 [36])
O
O
O
Br
Br
3i (30, 88, 116-118 [34])
3h (25, 84, 254-256 [34])
3g (30, 90, 136-138)
O
Cl
O
Cl
O
H3CO
OCH3
N
N
Cl
Cl
3l (30, 98, 163-164 [36])
3k (30, 93, 250-252 [35])
3j (30, 94, 160-162 [34])
O
OCH3
O
OCH3
O
O
O
O
O
OCH3
3m (35, 88, 106-108)
OCH3
3o (35, 92, 148-150)
3n (25, 79, 180-182 [37])
O
O2N
NO2
3p (25, 89, 160-162 [38])
aReaction conditions: aryl aldehyde and cyclic ketone, catalyst (7 wt %) water (3 mL) at reflux condition, btime in min,
cisolated yield in %, dmelting point in ºC, ereference
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R. C. Patil et al.
within 25-30 min with excellent yields. Melting point of all the synthesized prod-
ucts is compared with those reported in the literature [34–38].
Role of APP‑catalyst
Although we did not investigate the reaction mechanism, the plausible mechanism
for the α,α′-bis(substituted benzylidene)cycloalkanones (3) formation is depicted in
Scheme 2. The APP-catalyst containing the mixture of metal oxides and carbonates
is soluble to some extent in water which provides a number of Lewis basic sites
(O2−and OH) along with Lewis acid sites (M2+) for the activation of reactants to
forward the reactions in the proper direction. The carbonyl ketone (2) is activated
by Lewis basic sites along with Lewis acid sites may be simultaneously increas-
ing the driving force of aromatic aldehydes (1) to interact with activated ketone and
eliminated water molecules to aford the targeted α,α′-bis(substituted benzylidene)
cycloalkanones (3) product through formation of (E)-2-(argiomethylene)cyclohexan-
1-one intermediate (I). As a result, of the overall efect there is a rate enhancement
of the reaction.
Recycling of APP‑catalyst
Next, we investigated the reusability of catalyst. The reusability of catalyst is impor-
tant beneft for scale-up practical and industrial applications. A recycling experi-
ment was conducted using the 4-methoxybenzaldehyde and cyclohexanone as a
model reactants in water. After completion of the reaction, the solid product (3j)
obtained was separated by simple fltration followed by washing with distilled water
(2×5 mL). Whole fltrate containing APP-catalyst was collected separately and
extracted with ethyl acetate. The recovered aqueous layer containing APP-catalyst
was concentrated under vacuum to reduce 3 mL and directly used for the next cycle
with fresh reactants. The results obtained in our experiment (Fig. 8) confrmed that
the APP-catalyst could be reused up to ffth run with only negligible loss of activ-
ity. The presence of alkali metals in recycled catalytic system was evidenced by the
Scheme 2 Postulated role of APP-catalyst in the formation of α,α′-bis(substituted benzylidene)cycloal-
kanones
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Ash of pomegranate peels (APP): A bio-waste heterogeneous…
Reaction Mixture
(Product + APP + H2O)
x
F
O
u
l
i
f
l
t
e
e
r
R
MeO
OMe
H2O
CHO
O
Product (3j)
APP
2
+
2b
OMe
Filtrate extracted
with EtOAc
1b
Next run
Run 1st 2nd 3rd 4th 5th
Yield 94 94 93 92 92
Aqueous layer
containing APP
Fig. 8 Reusability of APP-catalyst
Fig. 9 EDX spectrum of recovered APP-catalyst
Scheme 3 Synthesis of 2-arylidene-1-tetralone derivatives
EDX analysis (Fig. 9), which revealed no appreciable change in the chemical com-
position of catalyst even after the ffth cycle.
Inspired by these tempting results obtained for condensation of aromatic alde-
hydes with cycloalkanones (Scheme 1) to aford the desired α,α′-bis(substituted ben-
zylidene)cycloalkanones, we decided to check the feasibility of APP-catalyst for syn-
thesis of 2-arylidene-1-tetralone under optimized reaction conditions (Scheme 3).
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R. C. Patil et al.
O
N
O
O
O
N
NR2
F
H2N
N
X
Anaglesic
Transquilizer
Antipsychotic
O
MeO
OMe
O
N
MeO
Antiviral
Neuroleptic
Fig. 10 Pharmaceutically important 1-tetralone derivatives
2-arylidene-1-tetralones exhibit important biological and pharmaceutical activities
(Fig. 10) such as tranquilizer [39], antifungal [40], neuromuscular blocking agent
[41], cytotoxic [42], inhibitory activity [43] and any others.
Unfortunately after 12 h, very trace amount of product was observed on TLC
when equimolar quantity of aromatic aldehyde and 1-tetralone was reacted. A very
few methods are reported in the literature where synthesis of 2-arylidene-1-tetralone
has been synthesized by the condensation of 1-tetralone with aromatic aldehydes at
various temperature conditions in the presence of diferent basic catalysts like NaOH
(0 °C) [44], KOH (RT), [45], piperidine (RT) [46] and also acidic catalysts such as
H2SO4, (refux) [47], H3PO4, (80 °C) [48], HCl (RT) [49]. Therefore, we decided to
optimize the reaction conditions for synthesis of 2-arylidene-1-tetralones.
For optimization study, the reaction between equimolar quantity of 4-methoxy-
benzaldehyde and 1-tetralone in the presence of APP-catalyst (7 wt%) was per-
formed at diferent temperature conditions and results are summarized in Table 3.
From results, it reveals that excellent result was obtained after 4 h, when model
reactants were stirred at 0 °C (Table 3, entry 7). Under the preceding optimized
conditions, we decided to prepare variously substituted 2-arylidene-1-tetralone as
Table 3 Optimization
Entry
Temp (°C)
Timeb (h)
Yieldsc (%)
of reaction temperature
for synthesis of
1
2
3
4
5
6
7
8
Refux
80
60
40
20
10
00
− 10
12
12
12
12
12
12
4
Trace
Trace
Trace
12
25
40
2-(4-methoxybenzylidene)-1-
tetralone (5a)a
92
92
4
aReaction conditions: 4-methoxybenzaldehyde and 1-tetralone, cata-
lyst (7 wt%) water (3 mL), btime, cisolated yield
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Ash of pomegranate peels (APP): A bio-waste heterogeneous…
Table 4 APP-catalyzed synthesis of 2-arylidene-1-tetralone derivatives (5a-j)a
O
O
O
OMe
Cl
5a (4b, 78c, 92-94d [50]e)
5b (4, 85, 120-122 [51])
5c (5, 75, 96-98 [50])
O
O
O
CN
NO2
N
5d (4, 75, 160-162 [48])
5e (3, 70, 182-184 [49])
5f (4, 70, 35-37 [50])
O
O
O
NO2
Cl
F
5g (3, 70, 118-120 [50])
5h (4, 82, 72-74 [50])
5i (3, 70, 106-108 [51])
O
OH
5j (4, 65, 125-127 [52])
aReaction conditions: aryl aldehyde and 1-tetralone, catalyst (7 wt %) water (3 mL) at room temperature, bTime in hr,
cIsolated yield in %, dMelting point in ºC, ereference
the unique small drug-like molecules. As shown in Table 4, the results indicate
that 1-tetralone bearing both electron-withdrawing and electron-donating groups
can be involved efcient in this reaction to aford the desired products (5a-i) in
high yields.
The reported methodologies (Table 5, entry 1–6) have used various catalysts
for condensation of 4-methoxybenzaldehyde and cyclohexanone. These meth-
odologies are convenient and aford the higher yield of product. However, these
methodologies require chemicals which are hazardous for handling, some of the
catalysts need toxic as well as corrosive chemicals for its synthesis, and their sep-
aration from the reaction mixture is much complicated. Compared to efciency
of the other reported methods, APP-catalyst found to be a suitable catalyst for the
synthesis of 2, 6-bis(4-methoxybenzylidene)cyclohexanone (Table 5, entry 7).
Table 5 Comparison of APP-catalyst with some previously reported catalyst for synthesis of 3j
Entry Catalyst
Catalyst loading Solvent (mL)
Temp. (°C)
Time
Yield (%)
References
1
2
3
4
5
6
7
I2
0.3 mmol
0.6 mmol
5.0 mmol
1 g
CH2Cl2
EtOH
CTAB/H2O
H20
R. T.
4.5 h
6.15 min
8 h
3 h
6 h
95
90
95
80
85
85
94
[53]
[34]
[54]
[55]
[6]
[56]
Present work
TiO2/HOAc
NaOH
Na/FAP
Cu(TFA)2.4H2O 2.2 mmol
SiO2-OK
Refux
60 °C
Refux
90 °C
Refux
Refux
–
1.0 mmol
7 wt%
EtOH
H2O
4 h
30 min
Ash of pome-
granate peels
1 3

R. C. Patil et al.
Conclusion
In conclusion, the present method reports green and highly efcient procedure for
the synthesis of α,α′-bis(substituted benzylidene)cycloalkanones and 2-arylidene-
1-tetralones under aqueous medium. Use of APP-catalyst obtained from renewable
bio-waste, mild reaction conditions and simple work-up without involvement of any
hazardous material quantify this method as an environmentally benign approach for
this condensation. The catalyst is new, attractive and inexpensive which can contrib-
ute to the development of more benign catalytic processes, reduced environmental
problems and proved to be a potential alternative to soluble bases.
Acknowledgements Authors are thankful to Indian Institute of Chemical Technology (IICT), Hyderabad
for NMR analysis.
Compliance with ethical standards
Confict of interest The authors declare that they have no confict of interest.
References
1. L. Zhang, S. Wang, E. Sheng, S. Zhou, Green Chem. 7, 683 (2005)
2. P. Anastas, J. Warner, Green Chemistry: Theory and Practice, vol. 30 (Oxford University Press,
New York, 1998)
3. M.B. Gawande, V.D.B. Bonifacio, R. Luque, P.S. Branco, R.S. Varma, Chem. Soc. Rev. 42, 5522
(2013)
4. Y. Wu, J. Hou, Y. Liu, M. Zhang, C. Tung, Y. Wang, Tetrahedron 72(12), 1511 (2016)
5. S.Z.D. Heirati, F. Shirini, A.F. Shojaei, Res. Chem. Intermed. 43, 6167 (2017)
6. D. Song, Y. Chen, R. Wang, C. Liu, H. Jiang, G. Luo, Prep. Biochem. Biotech. 39, 201 (2009)
7. J. Deli, T. Lonard, D. Szabo, A. Foldesi, Pharmazie 39, 539 (1984)
8. A.T. Dinkova-Kostova, C. Abeygunawardana, P. Talalay, J. Med. Chem. 41, 5287 (1998)
9. C. Piantadosi, I.H. Hall, J.L. Irvine, G.L. Carlson, J. Med. Chem. 16, 770 (1973)
10. S.F.P. Braga, E.V.P. Alves, R.S. Ferreira, J.R.B. Fradico, P.S. Lage, M.C. Duarte, T.G. Ribeiro,
P.A.S. Junior, A.J. Romanha, M.L. Tonini, M. Steindel, E.F. Coelho, R.B. de Oliveira, Eur. J. Med.
Chem. 71, 282 (2014)
11. A.A. Raj, R. Raghunathan, M.R. Sridevi Kumari, N. Raman, Bioorg. Med. Chem. 11, 407 (2003)
12. J.R. Dimmock, N.W. Hamon, K.W. Hindmarsh, A.P. Sellar, A.W. Turner, G.H. Rank, A.J. Robert-
son, J. Pharm. Sci. 65, 538 (1976)
13. R. Costi, R.D. Santo, M. Artico, G. Miele, P. Valentini, E. Novellino, A. Cereseto, J. Med. Chem.
50, 1973 (2007)
14. J.X. Wang, L. Kang, Y. Hu, B. Wei, Synth. Commun. 32(11), 1691 (2002)
15. J. Li, W. Yang, G. Chen, T. Li, Synth. Commun. 33, 2619 (2003)
16. T. Hosoya, A. Nakata, F. Yamasaki, F. Abas, K. Shaari, N. Lajis, H. Morita, J. Nat. Med. 66, 166
(2012)
17. S. Javanshir, M.M. Mojtahedi, J. Eslami, Curr. Chem. Lett. 3, 63 (2014)
18. M. Vashishtha, M. Mishra, S. Undre, M. Singh, D.O. Shah, J. Mol. Catal. A Chem. 396, 143 (2015)
19. H. Karimzadegan, B. Akhlaghinia, M.S. Ghasemzadeh, Iran. J. Catal. 9(2), 109 (2019)
20. M.S. Abaee, M.M. Mojtahedi, R. Sharif, M.M. Zahedi, H. Abbasi, K. Tabar-Heidar, J. Iran. Chem.
Soc. 3(3), 293 (2006)
21. L.T. An, J.P. Zou, L.L. Zhang, Catal. Communi. 9, 349 (2008)
22. U.P. Patil, R.C. Patil, S.S. Patil, React. Kinet. Mech. Catal. 129, 679 (2020)
23. M.B. Deshmukh, S.S. Patil, S.D. Jadhav, P.B. Pawar, Synth. Commun. 42, 1177 (2012)
1 3

Ash of pomegranate peels (APP): A bio-waste heterogeneous…
24. S.S. Patil, S.D. Jadhav, M.B. Deshmukh, J. Chem. Sci. 125, 851 (2013)
25. S.K. Shinde, S.A. Damate, S.T. Morbale, M.U. Patil, S.S. Patil, RSC Adv. 7, 7315 (2017)
26. S.K. Shinde, M.U. Patil, S.A. Damate, S.S. Patil, Res. Chem. Intermed. 44(3), 1775 (2018)
27. U.P. Patil, R.C. Patil, S.S. Patil, J. Heterocycl. Chem. 56, 1898 (2019)
28. S.R. Mali, S.K. Shinde, S.A. Damate, S.S. Patil, R. Soc, Open Sci. 5, 170333 (2018)
29. S.T. Morbale, S.K. Shinde, S.A. Damate, M.B. Deshmukh, S.S. Patil, Lett. Org. Chem. 15(1), 57
(2017)
30. S.T. Morbale, S.D. Jadhav, M.B. Deshmukh, S.S. Patil, RSC Adv. 5, 84610 (2015)
31. R.M. Appa, S.S. Prasad, J. Lakshmidevi, B.R. Naidu, M. Narasimhulu, K. Venkateswarlu, Appl.
Organometal Chem. (2019)
32. J. Lakshmidevi, R.M. Appa, B.R. Naidu, S.S. Prasad, L.S. Sarma, K. Venkateswarlu, Chem. Com-
mun. 54, 12333 (2018)
33. P.B. Hiremath, K. Kamanna, Curr. Microw. Chem. 6(1), 30 (2019)
34. E. Tabrizian, A. Amoozadeh, S. Rahmani, M. Salehi, M. Kubicki, Res. Chem. Intermed. 42(2), 531
(2015)
35. G.H. Mahdavinia, S. Rostamizadeh, A.M. Amani, M. Mirzazadeh, Green. Chem. Lett. Rev. 5(3),
255 (2012)
36. C.Y. Zhao, J.Y. Liu, Y. Wang, X.J. Zhao, B. Yuan, M.M. Yue, Synth. Commun. 1(44), 827 (2014)
37. R. Pal, IOSR-JAC 3(4), 74 (2013)
38. S. Ahmadi, A. Zare, M. Aali-Hosaini, M. Maghsoudi, S. Izadpanah, A. Parhami, M. Merajoddin,
Res. Chem. Intermed. 42(7), 6245 (2016)
39. W.M. Welch, C.A. Harbert, R. Sarges, W.P. Stratten, A. Weissman, J. Med. Chem. 20(5), 699 (1977)
40. T.A. Nakibl, V. Bezjakl, M.J. Meeganz, R. Chandy, Eur. J. Med. Chem. 25, 455 (1990)
41. D.F. Biggs, A.F. Casy, I. Chu, R.T. Coutts, Eur. J. Med. Chem. 19, 472 (1976)
42. J.R. Dimmock, M.P. Padmanilyam, G.A. Zello, J.W. Quail, E.O. Oloo, J.S. Prisciak, H.B. Kraatz,
A. Cherkasov, J.S. Lee, T.M. Allen, C.L. Santos, E.K. Manavathu, E. De Clercq, J. Balzarini, J.P.
Stables, Eur. J. Med. Chem. 37, 813 (2002)
43. A.S. Aboraia, B. Makowski, A. Bahja, D. Prosser, A. Brancale, G. Jones, C. Simons, Eur. J. Med.
Chem. 45, 4427 (2010)
44. V.P. Kumar, J. Renjitha, C.T. Fathimath Salfeena, K.T. Ashitha, S.K. Rangappa, V. Sunil, B.S.
Sasidhar, Chem. Biol. Drug. Des. 90, 703 (2017)
45. S.K. Mandal, A. Sarkar, J. Chem. Soc. Perkin Trans. 1, 669 (2002)
46. B. Hallgas, Z. Dobos, E. Osz, F. Hollosy, R.E. Schwab, E.Z. Szabo, D. Eros, M. Idei, G. Keri, T.
Lorand, J. Chromatogr. B 819, 283 (2005)
47. A. Sultan, A.R. Raza, M. Abbas, K.M. Khan, M.N. Tahir, N. Saari, Molecules 18, 10081 (2013)
48. T.M. Al-Nakib, T.L. Andras, F.R. Varghese, Med. Princ. Pract. 10, 191 (2001)
49. R. Kaur, M. Bansal, B. Kaur, Chem. Sci. J. 18, 1118 (2011)
50. S. Arora, A. Pareek, N. Agrawal, B.P. Nagori, IJRPC 3(4), 797 (2013)
51. R. Kamakshi, S. Swarna Latha, B.S.R. Reddy, Indian J. Chem. 49B, 944 (2010)
52. V. Tomeckova, J. Guzy, J. Kušnir, K. Fodor, M. Marekova, Z. Chavkova, P. Perjesi, J. Biochem.
Biophys. Methods 69, 143 (2006)
53. B. Das, P. Thirupathi, I. Mahender, K.R. Reddy, J. Mol. Catal. A Chem. 247, 182 (2006)
54. J.J. Shrikhande, M.B. Gawande, R.V. Jayaram, Catal. Commun. 9, 1010 (2008)
55. B. Mounir, F. Bazi, A. Mounir, H. Toufk, M. Zahouily, Green Sustain. Chem. 8, 156 (2018)
56. T.S. Jin, Y. Zhao, L.B. Liu, T.S. Li, Indian J. Chem. 45B, 1965 (2006)
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