Environmental benign synthesis of novel double layered nano catalyst and their catalytic activity in synthesis of 2-substituted benzoxazoles

Article abstract of DOI:10.1016/j.catcom.2017.01.005

Synthesis of Cu-Al hydrotalcite by co precipitation method is being described. Synthesized nano catalyst has been characterized by powder X-ray diffraction, scanning electron microscopy, FT-IR and thermogravimetric analyses which confirm hydrotalcite-like structure. Effect of molar concentration, catalyst loading, reaction time and catalytic activity have been investigated in the synthesis of benzoxazoles under solvent free conditions using 2-amino phenol and benzoyl chloride. The influence of the hydrotalcite and their different amounts on reactivity was studied. Catalyst can be recycle and used for further reaction without losing its activity.

Full text of DOI:10.1016/j.catcom.2017.01.005

Accepted Manuscript
Environmental benign synthesis of novel double layered nano
catalyst and their catalytic activity in synthesis of 2-substituted
benzoxazoles
Ruchi Gupta, Pramod K. Sahu, S.K. Srivastava, D.D. Agarwal
PII:
DOI:
Reference:
S1566-7367(17)30012-2
doi: 10.1016/j.catcom.2017.01.005
CATCOM 4904
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
20 October 2016
28 December 2016
4 January 2017
Please cite this article as: Ruchi Gupta, Pramod K. Sahu, S.K. Srivastava, D.D. Agarwal ,
Environmental benign synthesis of novel double layered nano catalyst and their catalytic
activity in synthesis of 2-substituted benzoxazoles. The address for the corresponding
author was captured as affiliation for all authors. Please check if appropriate.
Catcom(2017), doi: 10.1016/j.catcom.2017.01.005
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ACCEPTED MANUSCRIPT
Environmental benign synthesis of novel double layered nano catalyst and
their catalytic activity in synthesis of 2-substituted benzoxazoles
Ruchi Guptaa, Pramod K. Sahu*,a,b, S. K. Srivastavaa, D. D. Agarwala,b
aSchool of Studies in Chemistry Jiwaji University, Gwalior, Madhya Pradesh, India
bDepartment of Industrial Chemistry, Jiwaji University, Gwalior-474011, Madhya Pradesh, India
*To whom correspondence should be addressed: Email: sahu.chemistry@gmail.com (Pramod K. Sahu)
Abstract
Synthesis of Cu-Al hydrotalcite by co precipitation method is being described. Synthesized nano
catalyst has been characterized by powder X-ray diffraction, scanning electron microscopy, FT-
IR and thermogravimetric analyses which confirm hydrotalcite-like structure. Effect of molar
concentration, catalyst loading, reaction time and catalytic activity have been investigated in the
synthesis of benzoxazoles under solvent free conditions using 2-amino phenol and benzoyl
chloride. The influence of the hydrotalcite and their different amounts on reactivity was studied.
Catalyst can be recycle and used for further reaction without losing its activity.
Keywords: Double Layered Nano Catalyst, Reusability, Benzoxazole, Green Synthesis,
Heterogeneous catalyst.
1. Introduction
Layered double hydroxides are the anionic clay in which divalent cations within brucite-
like layers are replaced by trivalent cations. The resulting positive charge is compensated by hy
drated anions located in the interlayer space between two brucite sheets. The general formula for
x+
these materials is [M(II)1 – x N(III)x ( OH)2] [ Anx/ n] mH2O, here M(II) and N(III) are di-and
trivalent metal cations respectively, which occupy octahedral positions in hydroxide layers. An is
2-
-
an exchangeable anion, such as CO3 , NO3 and Cl-, etc. [ 1_ 4] Copper-containing hydrotalcites
represent a rather peculiar system in this family of compounds, probably due to the well-known
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tendency of copper to form distorted octahedra because of a Jahn–Teller effect. Consequently,
much effort has been made to prepare hydrotalcites containing copper, to be used for different
purposes. Recently, a number of researchers have shown that the copper based catalysts of
hydrotalcite derived mixed oxides give highly stable activity for synthesis of higher alcohols and
hydrocarbons, water-gas shift reaction, and NOx and SOx reduction [5–9]
Benzoxazoles are an important class of heterocyclic compounds that have many
applications in medicinal chemistry. For example, benzoxazole derivatives have been
characterized as melatonin receptor agonists,[10] amyloidogenesis inhibitors,[11] Rho kinase
inhibitors,[12] and antitumor agents.[13] In addition to their use in medicinal chemistry,
benzoxazoles are recognized as an important scaffold in fluorescent probes such as anion and
metal cation sensors.[14] It is encountered in a number of natural products and are used in drug
and agrochemical discovery programs, as well as for a variety of other purposes. For example,
the benzoxazole core structure is found in a variety of cytotoxic natural products, such as the
UK-1,[15] AJI9561,[16] and salvianen.[17] Recent, medicinal chemistry applications of
benzoxazoles have been reported which include the cathepsin S inhibitor,[18] selective
peroxisome proliferator-activated receptor γ antagonist JTP-426467.[19]. Other applications of
benzoxazoles include their use as herbicides, such as Fenoxaprop, and as fluorescent whitening
agent dyes such as bisbenzoxazolyl ethylenes and arenes.[20]
There are two general methods for synthesizing 2-substituted benzoxazoles. One is the
coupling of 2-aminophenols with carboxylic acid derivatives, which is either catalyzed by strong
acids [21] or requires microwave conditions.[22] The other is the oxidative cyclization of
phenolic Schiff bases derived from the condensation of 2-aminophenols and aldehydes. In the
latter reactions, various oxidants such as DDQ,[23] Mn-(OAc)3,[24] PhI(OAc)2,[25]
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Th+.ClO4,[26] BaMnO4,[27] NiO2,[28] Pb-(OAc)4[29], CuFe2O4 NPs [30] Poly(melamine-
formaldehyde),[31] Au/TiO2,[32] CuI,[33] I2-TBHP.[34] have been reported. However, all of
these oxidants are required in stoichiometric or excess amounts relative to their respective
substrates. Synthesis of 2-substituted benzoxazole using amino phenol and benzoyl chloride has
been reported in literature with few catalysts having many drawbacks such as longer reaction
time, highly toxic reagents or harsh reaction conditions, strong acids, higher temperature and low
yield.[35-42] Therefore, a more effective process is needed.
To our knowledge, hydrotalcite has not been used as the catalyst for the synthesis of
benzoxazoles using amino phenol and benzoyl chloride under solvent free conditions. Due to
well-defined surface active sites, hydrotalcites are currently receiving considerable attention
because of their unique properties such as reusability, ease of handling and separation with their
environment friendliness. In this study, we present the preparation and characterization of Cu-Al
hydrotalcites catalysts as well as their catalytic application for the benzoxazole synthesis in
solvent free condition resulting in excellent yield.
2. Materials and Method
2.1 Experimental
1
The H NMR spectra were measured using BRUKER AVANCE II 400 NMR spectrometer with
o
1
tetramethylsilane as an internal standard at 20-25 C; data for H NMR are reported as follows:
chemical shift (ppm), integration, multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m,
multiplet, and br, broad), coupling constant (Hz). IR spectra were recorded by SHIMADZU; IR
spectrometer of sample dispersed in KBr pellet or Nujol is reported in terms of frequency of
absorption (cm-1). E-Merck pre-coated TLC plates and RANKEM silica gel G were used for
preparative thin-layer chromatography. Melting points were determined in open capillaries and
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are uncorrected. All the metal salts, 2-amino phenol, benzoyl chloride were all of A. R. grade and
obtained from Fisher scientific and Qualigen chemical company.
2.2 Characterization Techniques
The structures of the catalysts were studied by XRD, FT-IR, SEM and TGA methods. PXRD was
carried out in a Philips X‟Pert MPD syste. The operating voltage and current were 40 kV and 30
mA, respectively. FT-IR absorption spectra of the samples were recorded in a Perkin-Elmer FT-
IR spectrometer (Model-FT-1730). The powdered samples were ground with KBr in 1:20 ratio
and pressed into pellets for recording the spectra. Thermogravimetric analysis (TGA) was carried
out in Mettle TGA/SDTA 851e and the data were processed using Stare software, in flowing
o
nitrogen in a flow rate of 60 ml/min and at a heating rate of 20 C/min. The electron microscopic
study has been done with scanning electron microscope (Leo series VP1430). The samples were
coated with gold using sputter coating before analysis to avoid charging effects during recording.
Analyses were carried out with an accelerating voltage of 20 kV and a working distance of 17
mm, with magnification values up to 100,000 xs. NMR spectra were recorded by using Bruker
AV II 400 NMR Spectrometer using DMSO solvent and TMS as an internal standard in the range
of δ 0-10 ppm. Mass spectra were recorded by using PDL/ARD-062 mass spectrometer in the
range of 100-500 m/z.
3. Experimental
3.1 Preparation of hydrotalcites
Al-Cu-Cl- hydrotalcite having ratio 1:3 has been prepared by the addition of 1 molar NaOH
solution at a constant rate (about 1mL/minute) to a mixed solution of 0.1 molar AlCl3.6H2O
(1.69 g) and 0.3 molar CuCl2.2H2O (3.58 g). This procedure resulted in increase in pH and
NaOH solution was continuously added into the solution until a pH about 10-11 value was
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reached at which well crystallized particles were observed. After this slurry was stirred with
heating for two hours and obtained slurry was kept for cooling and setting of crystal then filtered
o
and washed with a large amount of distilled water. The filtered cake was dried in oven at 100 C
for 24 hours.
Al-Cu-Cl- hydrotalcite having ratio 1:2, using 0.1 molar AlCl3.6H2O (1.69 g) and 0.2 molar CuCl2.2H2O
(2.38 g) and following same procedure as for preparation of 1:3 ratio was used.
Al-Cu-Cl- hydrotalcite having ratio 1:4, using 0.1 molar AlCl3.6H2O (1.69 g) and 0.4 molar CuCl2.2H2O
(4.77 g) and following same procedure as for preparation of 1:3 ratio was used.
3.2 Synthesis of 2 phenyl benzoxazole
To a 100 ml round-bottomed flask benzoyl chloride (0.108 g, 1 mmol) and 2-amino phenol (0.15
mL, 1.3 mmol) and hydrotalcite (0.10 g) were added and the reaction mixture heated at 60 °C for
60 minutes under solvent free conditions. Reaction was monitored by TLC using ethyl acetate and
hexane (1:4 ratios respectively) as a solvent and then reaction mass was cooled at room
temperature and acetone was added followed by filtration.
3.3 Gram scaled-up process for 2 phenyl benzoxazole (3a)
A 500 mL, three-necked, round-bottom flask equipped with a thermometer and water condenser
was charged with benzoyl chloride (100 mmol, 10.8 g), 2-amino phenol (130 mmol, 15.0 mL) and
o
hydrotalcite (10 g). The resulting mixture was refluxed at 60 C under solvent free conditions.
The reaction was monitored by TLC analysis and completed within 60 minutes. After completion
the reaction mass was cooled at room temperature and acetone was added followed by filtration.
2 phenyl benzoxazole (3a) was obtained in 99% yield with mp 98-101 oC. The characteristic data
for the isolated product were found to be same as given in the supporting information.
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4. Results and Discussion
Characterization of catalyst
The sharp peak recorded at 2θ=35.1° is ascribed to diffraction by planes (003) of a
hydrotalcite structure. For HT 3.0, copper hydrotalcite some traces of malachite, this agrees with
the data reported in the literature that a divalent/trivalent molar ratio equal or larger than 2.0 is
needed to prepare crystallographically pure hydrotalcites (figure 1). Assuming the 3R packing of
the layers, lattice parameter c corresponds to three times the value of d (003), i.e., c =39.5 Å.
Lattice parameter corresponds to the average closest metal–metal distance within a layer, and is
calculated as twice the position of the diffraction maximum due to planes (110), corresponding
to the first peak of a doublet recorded around 2θ=65°; is due to diffraction by planes (110). This
maximum is hardly seen in the diagrams because its intensity is usually much weaker than that of
the basal diffraction maxima.
S9
11000
3e+004
2e+004
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
1e+004
0e+000
0
10
20
30
40
50
60
70
80
90
20
40
60
80
2-Theta in degree
2-theta (deg)
Fig 1. XRD of synthesized hydrotalcite
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The FT–IR spectrum of sample Cu-Al is characteristic of a hydrotalcite-like solid with
Cl- as the interlayer anion. The broad band around 3450 cm-1 is due to OH stretching mode of
hydrogen-bonded hydroxyl groups and of interlayer water molecules. This broad band includes a
broad shoulder below to 3000 cm-1 which has been ascribed to the OH stretching mode of
hydroxyl groups hydrogen bonded to interlayer anions. The medium intensity band close to 1625
cm-1 is due to the bending mode of interlayer water molecules (figure 2 in supporting
information). Bands at lower wave numbers are due to vibrational modes of M–O, M–O–M, and
O–M–O species in the layers.
Figure 3 (a) in supporting information shows the TG diagrams for the Cu-Al-Cl-
hydrotalcite samples. There was a considerable weight loss (≈10%) between 150 and 200 °C
suggesting the thermal decomposition of the HTs sample and a small loss (≈11%) at about 250
°C. New weight losses were detected at higher decomposition temperatures (800–1000°C) The
changes in weight for these samples at higher temperatures are 14%, and the total weight loss
during the calcination process was around 35% for the Hts. The TG curves of hydrotalcites with
interlayer anions and without oxidisable cations in the layer show first weight loss, usually
ascribed to removal of interlayer water molecules, and a second weight loss, completed around
250 °C, which corresponds both to removal of water through condensation of layer hydroxyl
groups, and carbon dioxide loss, from interlayer carbonate.
Fig 3 (b) shows SEM image of Cu-Al-Cl- hydrotalcite in which crystal structure as
platelets but it has seen that, the catalyst surface was not uniform and a large number of cavities
and crevices could be clearly observed.
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Chemistry
A facile method has been proven for preparation of 2 phenyl benzoxazole. Herein we
have developed a more practical and rapid method for synthesis of 2 phenyl benzoxazole using
nano catalyst under solvent free conditions (Scheme 1). To optimize the reaction conditions,
variety of catalysts were screened in a model reaction of benzoyl chloride and 2-amino phenol
(table 1). From table 1, it has been found that best yield was obtained with Cu-Al Cl- hydrotalcite
with lower time as compared to other metal catalysts (table1, entries 3). Other metal oxide,
hydroxide and chlorides give moderate yield of final product (table1, entries 4-10).
Scheme 1. Synthesis of 2 phenyl benzoxazole
Table 1. Synthesis of 2 phenyl benzoxazole using various catalysts
run
1.
2.
3.
4.
5
catalyst
Yield (%)
Al-Zn-Cl-
56
76
99
41
56
51
42
59
61
63
3-
Al-Zn-PO4
Al-Cu-Cl-
AlCl3
SiO2
6
MnO2
7
Al(OH)3
Ca(OH)2
Al2O3
8
9
10
Mg(OH)2
Further to identify the catalyst loading, different amounts of loading (table 2, entries 1-5
in supporting information) was used Table 2 shows that at catalytic concentration 100 mg of
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catalyst (HT) was suitable to promote the reaction efficiently (table 1, entry 4 in supporting
information). An increment in catalyst concentration more than 100 mg did not show effective
improvement in product yield (table 1, entry 5 in supporting information). It concluded that best
catalytic amount for reaction was 100 mg and further optimized amount has been used for
investigation of other reaction conditions.
As shown in table 3 (in supporting information), at 40°C yield was 90% and on
increasing the temperature yield is increased at it is stable at 60 °C and 80 °C. It concluded that
60° as a ideal temperature but on studying the time effect it will shown that at 15 min yield was
65%. On increasing the time, yield is also increased and is stable after 60 minutes, it concluded
that 60 min at 60 oC is ideal time for reaction condition.
As shown in Table 4, there are few reports in literature for synthesis of benzoxazole
derivatives using amino phenol and benzoyl chloride using homogeneous and heterogeneous
catalysts, In order to show the merit of the present protocol, Cu-Al hydrotalcite as recyclable
catalyst has been compared with reported protocols for the synthesis of benzoxazole derivatives.
In contrast with other existing methods, the present methodology offers several advantages such
as excellent yields, a simple and easy synthesis procedure, simple work-up, reusability of catalyst
and greener conditions. The results clearly show that, catalysts Co-NPs with K2CO3, In(OTf)3,
SAB-Pr-SO3H, NaHSO4-SiO2, TiO2-NPs, Cu(OAc)2 with KHCO3 and KNO3 required longer
reaction time, harsh reaction conditions, higher temperature and often lower yield. On the other
hand, catalysts [bbim]BF4 and [Hbim]BF4 (ionic liquids) reacted in the low yield. The drawback of
ionic liquids is that it cannot be removed by distillation and their limited solubility in water
restricts their use. They have high cost and also acute toxicity for aquatic organism and
human.[43-45] As seen in Table 4, present procedure is simpler, more efficient, without the need
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for toxic solvents, and low amount of the catalyst. It shows that Cu-Al is a powerful catalyst for
the synthesis of benzoxazole derivatives, suggesting that present procedure is a clean and
environmentally friendly reaction.
Table 4. Comparison of Cu-Al HT with the reported catalysts
Entry
Catalyst
Co-NPs + K2CO3
In(OTf)3
SAB-Pr-SO3H
NaHSO4-SiO2
Solvent Conditions Time (h/min) Yield(%)
Reference
[35]
1
2
3
4
5
6
7
8
EtOH
─
80 oC
110 oC
Reflux
100 oC
140 oC
28 oC
8.0 h
15 h
96
93
91
92
77
92
94
99
[36]
[37]
[38]
[39]
[40]
[41]
AcOH
─
8.0 h
12 h
Cu(OAc)2 + KHCO3 + KNO3
[bbim]BF4 and [Hbim]BF4
TiO2-NPs
PhCl
─
─
20 h
40 min
17 min
2.0 h
90 oC
60 oC
Cu-Al HT
─
Present work
As shown in table 5, the present methodology proved to be efficient for the synthesis of
bezoxazole derivatives in good yields. The benzoyl chloride having different substituent like 4-
OMe, 3,4-OMe, 4-NO2, 2-Cl and hetero-aromatic acyl chloride form different benzoxazole as
shown in table 5, electron donating group and heteroaromatic acyl chloride gave the highest
yield (table 5, entry 4, 5, 7 and 8) and electron withdrawing group retarded the reaction and gave
lower yield (table 5, entry 2, 3). On the other hand, substituted amino phenols have shown
excellent yield (table 5, entry 6, 9 and 10). The structures of the representative derivatives were
determined from their spectral analysis (1H NMR, 13C NMR and MS).
Table 5. Cu-Al HT catalyzed synthesis of benzoxazole derivatives
Entry
1
R’
R
Product
Yield (%)a Time (min)
99
60
3a
2
75
90
3b
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3
4
74
60
3c
91
90
3d
5
6
87
96
90
60
3e
3f
7
8
9
97
94
96
30
30
60
3g
3h
3i
10
94
60
3j
aIsolated Yield
Recyclability of the catalyst is an important task in industrial applications. Therefore
reusability of hydrotalcite was investigated for five runs (table 6, entries 1-5 in supporting
information) in a model reaction benzoyl chloride and 2-amino phenol were reacted in presence
of 100 mg of hydrotalcite as catalyst. After completion of reaction, the contents were filtered to
recycle the hydrotalcite catalyst. Recycled hydrotalcite was washed with methanol to remove
organic impurities. Hydrotalcite catalyst can be readily recovered and reused for five runs. It was
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found that the reactivity of the catalyst was constant upto 3 runs and decreases in further runs
which may be due to handling loss of catalyst amount.
Leaching test
For confirmation of leaching , recycled hydrotalcite was analyzed for leached metal
content by ICP emission spectroscopy. No metal was detected. These results confirmed that the
metal leaching did not occur. Hydrotalcite like mixed oxide was found to be thermally and
mechanically stable and no significant difference was observed in particle size and morphology
of the used catalyst as evidenced by SEM.[46,47] However, lower yield was found with recycled
hydrotalcite, it may be due to handling loss during workup in subsequent cycles. To ensure the
sustainability of structure of recovered hydrotalcite (figure 4), XRD has been carried out which
showed similar profile as exhibited by fresh catalyst which confirmed that layered structure of
hydrotalcite was maintained after the reaction.
3e+004
2e+004
1e+004
0e+000
20
40
60
80
2-theta (deg)
Fig 4. XRD pattern of recovered hydrotalcite
5. Conclusion
In conclusion, we have developed green methodology for eco-friendly synthesis of
variety of substituted benzoxazoles under solvent free conditions. The prepared catalyst were
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characterized with SEM, TG, IR and XRD showing the strong basic sites in double layers and
coordinatively unsaturated O2- ion acting as basic sites in the calcined hydrotalcite may be
responsible for their catalytic activity. This is first attempt to synthesize substituted benzoxazoles
using benzoyl chloride and amino phenol in the presence of hydrotalcite as heterogeneous
catalyst which is easily separable and recyclable up to five runs. Compared to previously
reported methods, moreover, the mild reaction conditions, easy work-up, clean reaction profiles,
lower catalyst loading and cost efficiency render this approach as an interesting alternative to the
existing methods.
7. Acknowledgement
The Authors express thanks to DRDE, Gwalior (M.P), SAIF Chandigarh and IUC-Indore for
carrying out the spectral analysis.
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Scheme legends
Fig 1. XRD of synthesized hydrotalcite
Fig 2. FT-IR of synthesized hydrotalcite
Fig 3. (a) TG and (b) SEM image for hdrotalcite
Fig 4. XRD pattern of recovered hydrotalcite
Scheme 1. Synthesis of 2 phenyl benzoxazole
Table 1. Synthesis of 2 phenyl benzoxazole using various catalysts
Table 2. Effect of catalyst concentrationa
Table 3. Effect of temperature and timea
Table 4. Comparison of Cu-Al HT with the reported catalysts
Table 5. Cu-Al HT catalyzed synthesis of benzoxazole derivatives
Table 6. Recyclability of catalyst
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Graphical abstract
Research Highlights
 Novel catalytic system for synthesis of benzoxazoles.
 Characterization by XRD, TG, IR and SEM.
 Synthesis using heterogeneous catalyst.
 Sustainable approach under solvent free conditions.
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