Facile synthesis of ZnAl2O4 nanoparticles: Efficient and reusable porous nano ZnAl2O4 and copper supported on ZnAl2O4 catalysts for one pot green synthesis of propargylamines and imidazo[1,

Article abstract of DOI:10.1039/c5ra20812b

A simple, facile and efficient route was developed for the synthesis of nano ZnAl₂O₄ using ethanolamine. ZnAl₂O₄ nanoparticles were found to be smaller when calcined at 500 °C than at 700 °C. The synthesized nan

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Facile synthesis of ZnAl2O4 nanoparticles: Efficient and
reusable porous nano ZnAl2O4 and Copper supported on
ZnAl2O4 catalysts for one pot green synthesis of
propargylamines and imidazo[1,2-a]pyridines by A3
coupling reactions
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Triveni Rajashekhar Mandlimath and Kulathu I. Sathiyanarayanan*
A simple, facile and efficient route was developed for the synthesis of nano
ZnAl2O4 using ethanolamine. ZnAl2O4 nanoparticles were found to be smaller
when calcined at 500 °C than at 700 °C. The synthesized nano ZnAl2O4
exhibited a high surface area of 147 m2/g with pore volume 0.2 cm3/g.
ZnAl2O4 nanoparticles were found to be spherical in shape with size ranging
from 3 ꢀ 7 nm. For the first time, we explored the catalytic activity of nano
ZnAl2O4 for the synthesis of propargylamines by A3 coupling of aromatic
aldehydes, piperidine and phenyl acetylene. High yields were achieved without
any side product. We developed Cu/ nano ZnAl2O4 and utilized it for
imidazo[1,2ꢀa]pyridines synthesis by three component coupling of aromatic
aldehydes, 2ꢀaminopyridine and phenylacetylene under N2 atmosphere. We
achieved good yields, and both nano ZnAl2O4 and Cu/ nano ZnAl2O4 were
recycled for five times successfully. Both the protocols were simple, one pot,
solventꢀfree, economical and involved no additive. They could be an
alternative to the existing protocols which involve homogeneous and expensive
noble metal catalysts for these reactions.
Propargylamines are the important key components of various
natural products,1 versatile precursors for the synthesis of
INTRODUCTION
Multicomponent coupling reactions (MCRs) are the potential tool
to synthesize diverse complex organic scaffolds from simple
organic moieties via oneꢀpot process. These MCRs have gained
extensive interest of researchers because of their uniqueness in
yielding high atom economy and often high selectivity. In recent
times, intense investigation for the development of ecoꢀfriendly
solvent free MCRs have been a great concern in order to reduce
environmental pollution caused by hazardous organic solvents.
Among the MCRs, A3 coupling of (i) aldehyde, alkyne, and amine
and (ii) aldehyde, alkyne, and 2ꢀaminopyridine via activation of a
terminal alkyne CꢀH bond have been great importance in recent
years. The resulting propargylamines and imidazo[1,2ꢀa]pyridines
are nitrogen containing compounds with diverse applications:
quinolines,2a
indolizines,2boxazoles,2c
pyrroles,2d
and
pyrrolidines,2e and also potential building blocks for the synthesis
of the therapeutic drug molecules such as isosteres,3a allylamines,3b
βꢀlactams,3c
conformationally
restricted
peptides,
and
oxotremorine analogs.3d Recently propargylamine derivatives have
attracted attention due to their excellent pharmacological activity.
4b
They are strong neuroprotective4a,
and antiꢀapoptotic agents4c.
Propargylamine derivative rasagiline is used for treating early
Parkinson's disease5. Whereas, imidazo[1,2ꢀa]pyridines are the
versatile scaffolds mainly occurred in wide range of bioactive
molecules and also known for their antiviral,6a antiꢀ
inflammatory,6b,6c analgesic,6c antipyretic,6c antiulcer6d and
antibacterial properties.6e Commercial drugs such as Alpidem
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(anxiolytic agent),7a Zolpidem (insomnia),7bOlprinone (for the first report for nano ZnAl2O4 synthesis using ethanolamine and
treatment of acute Heart failure),7c and Minodronic acid (for the protocols for the one pot synthesis of propargylamines and
treatment ofosteoporosis)7d contain imidazo[1,2ꢀa]pyridine moiety. imidazo[1,2ꢀa]pyridines using nano ZnAl2O4 and Cu/nano
In addition to the above applications, imidazo[1,2ꢀa]pyridine
derivatives have incurred significant importance as central ligands very simple. Being solvent free, environmentally friendly, the
in the field of electronic devices.8 protocols for A3 coupling reactions utilize low cost reusable
ZnAl2O4respectively. The synthetic route of nano ZnAl2O4 was
Conventional method of synthesizing propargylamines requires catalysts.
the generation of metallated alkynes utilizing various strong bases
such as alkoxides9a, hydroxide,9b LiAlH4,9c butyl lithium9d,9e
,
Results and discussion
LDA9e and Grignard reagents9f and attack of the generated
metallated alkynes to imines. The major drawbacks of this protocol
are the need of highly moistureꢀsensitive reagents in stoichiometric
quantity and harsh reaction conditions. In recent years, A3 coupling
of aldehydes, amines and alkynes via CꢀH activation have been
developed as alternative to the traditional method, wherein water is
the only byproduct. Variety of homogeneous catalysts like
Zn(OAc)2,10a AgI,10b AuCl,10c AuI,10c AuCl3,10c AuBr3,10c FeCl3,10d
CdI2,10e InCl3,10f InBr3,10g CuCl,10h CuBr,10h CuI,10h NiCl2,10i
Hg2Cl2,10j Au(III) complexes,11 Ag(I) complexes12 have been
applied. Theses catalysts mostly require hazardous solvents like
acetonitrile, toluene, and tedious workup process and often need
inert atmosphere. In order to replace the homogeneous catalysts,
in recent years, heterogeneous catalysts have been employed: Au
nanoparticles,13a Ag nanoparticles,13b Au/CeO2,14 Au/ZrO2,14 Au
nanoparticles stabilized on montmorillonite,15 Au and Ag
nanoparticles on Egg shell,16 Ag immobilized on ZnO
nanoparticles,17nanocrystallineMgO stabilized Au nanoparticles,18
polystyrene supported NHCꢀAg(I) catalyst,19 Au nanoparticles on
Powder XRD and BET analysis
Figures 1a and 1b display powder XRD patterns of ZnAl2O4
calcined at 500 °C (ZAO5) and ZnAl2O4 calcined at 700 °C
(ZAO7) respectively. Both materials were phase pureand
crystallized in face centered cubic phase. All the peaks were
indexed based on the standard ICDD data (# 821043). XRD peak
broadening of ZAO7 was found to be lesser than that of ZAO5.
This indicates the crystallite size of nano ZnAl2O4 increased with
increase in calcination temperature. The average crystallite size of
ZAO5 and ZAO7 determined from Scherrer’s formula was 5 nm
and 7 nm respectively.XRD pattern (Fig. 2) of Cu/ZAO5 affirmed
the presence of copper diffraction peaks (2θ = 43.31 and 50.44)
along withZnAl2O4 peaks. No other metal oxide peaks were
observed in XRD. From the BET method, the specific surface area
and pore volume of ZAO5 and ZAO7 were found to be 147 m2/g,
0.2 cm3/g and 100 m2/g, 0.14 cm3/grespectively. This evidenced
decrease in the surface area and pore volume of ZnAl2O4 upon
increasing the calcination temperature from 500 °C to 700 °C.
Al2O3,20
Cu
nanoparticles
stabilized
on
modified
montmorillonite.21 Although these are heterogeneous in nature,
they are expensive and often require toxic toluene, THF solvents,
prolonged duration to achieve good yields and metals often lost
during the reaction. Ionic liquids immobilized catalysts containing
imidazolium molecule with BF4 or PF6 anions have been
reported22. These catalysts have serious limitation due to their high
cost and disposable problem as they are highly toxic. Metal oxides
such as Cu/SiO2,23 CuꢀZeolite,24 Zinc titanate nanopowder25 and
26
Co3O4 and copper aluminium based nanocomposites27 have been
investigated for propargylamines synthesis. However, most of the
catalysts need organic solvent and require long time to achieve
high yields.
Various protocols are available in the literature for the synthesis of
imidazo[1,2ꢀa]pyridines using CuꢀMOF,28 Cu(OTf)2,29 CuCl,29
InBr3/Et3N,30 CuSO4ꢀglucose,31 Iodine,32CuI/NaHSO4ꢀSiO2,33
CuSO4/TSOH,34 ZnCl2/CuCl35 as catalysts. These protocols suffer
from serious issues such as need of homogeneous catalysts, long
duration and often require additives (like glucose, TsOH and Et3N)
along with metal catalysts.
Considering the biological and therapeutic importance of
propargylamines and imidazo[1,2ꢀa]pyridines, and also the
inefficiency of existing protocols for their synthesis, in
continuation of our previous reports,36, 37 herein, we developed a
facile synthetic method for nano porous ZnAl2O4 with large
surface area and employed it as an efficient catalyst for the
synthesis of propargylamines. Cu nanoparticles supported on the
synthesized nano ZnAl2O4 were efficiently used as catalyst for
imidazo[1,2ꢀa]pyridines. To the best of our knowledge, this is the
Fig. 1 Powder X-ray diffraction patterns of (a) ZAO5 and (b) ZAO7
2 | J. Name., 2012, 00, 1-3
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Mn+ꢀO2ꢀpair) and strong (due to isolated O2ꢀ) basic sites on the
catalyst’s surface respectively.38 The total basicity of the catalyst
was found to be 2.5 mmol CO2/g.
XPS analysis was carried out for the sample Cu/ZAO5 to know
the oxidation state of copper. Fig. 7 shows the XPS spectrum of
Fig. 2 Powder X-ray diffraction pattern of Cu/ZAO5
In the present work, ethanolamine acted as complexing as well
as precipitating agent. The gradual addition of ethanolamine led to
the formation of the complex with zinc nitrate and aluminium
nitrate, which upon calcinations resulted in nanosized particles of
ZnAl2O4. The evolution of NH3 and CO2 gases during calcinations
left the pores in the catalysts.In our previous report36, we
synthesized ZnAl2O4 in the absence of ethanolamine. From the
micrographs and powder Xꢀray analysis, it was identified that the
particles were in the range of 5 µm. Hence, these observations
indicated the presence of ethanolamine controlled the ZnAl2O4
particle size.
Fig. 3 SEM images of (a) ZAO5 and (b) Cu/ZAO5
In the case of Cu/ZnAl2O4, surface area was found to be 50
m2/g with pore volume 0.07 cm3/g. This confirmed the occupancy
of copper over the surface and pores of nano ZnAl2O4.
Microscopic and TPD analysis
SEM images of ZAO5 (Fig. 3a) and Cu/ZAO5 (Fig. 3b) showed
aggregation of the particles. EDX spectra (supplementary data)
affirmed the presence of Zn, Al, O and Zn, Al, Cu and O elements
in the catalysts ZAO5 and Cu/ZAO5 respectively. The atomic
percentage matched with the theoretical values. EDX spectra of
ZAO5 and Cu/ZAO5 showed the absence of C and N peaks,which
indicates the absence of ethanolamine.
TEM images of ZAO5 and Cu/ZAO5are shown in Fig. 4a and
4b.The particles were spherical in shape. Crystalline nature and
homogeneous distribution of ZAO5 particles were evident from
Selected Area Electron Diffraction (SAED) Pattern (Fig. 4a inset).
Presence of copper nanoparticles on ZAO5 was identified by
TEMꢀEDX analysis (Supplementary data). Crystalline nature of
the Cu/ZAO5 particles was seen from Selected Area Electron
Diffraction (SAED) Pattern (Fig. 4b inset). The obtained histogram
revealed the narrow size distribution of ZAO5 nanoparticles with
3ꢀ7 nm size (Fig. 5).
NH3ꢀTPD pattern (Fig. 6a) shows two peaks at 194 ºC and 367
ºC. The ZAO5 possessed medium acidic sites. The total acidity
was 5 mmol py/g. CO2 ꢀ TPD pattern (Fig. 6b) exhibited three
peaks at 154 ºC, 334 ºC and 438 ºC. The peak at 154 ºC was
associated with weak basic site (surface hydroxyl group). The
peaks at 334 ºC and 438 ºC were associated with medium (due to
Fig. 4 TEM images of (a) ZAO5 and (b) Cu/ZAO5; Inset show respective electron diffraction
patterns
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Cu/ZAO5. The peaks appeared at 943 eV and 962 eV,
characteristic satellite peaks, belong to Cu2+. The peakappeared at
953 eV associated with Cu 2p1/2.39Thisconfirmed that the copper
underwent surface oxidation and that the copper surface was in the
form of CuO.
Catalytic role of nano ZnAl2O4 and Cu/nano ZnAl2O4 for A3
coupling reactions
Initially we investigated the catalytic activity of commercial ZnO,
Al2O3, bulk ZnAl2O4and synthesized nano ZnAl2O4 for the
propargylamine synthesis by refluxing benzaldehyde (3 mmol),
piperidine (3.3 mmol) and phenylacetylene (3.6 mmol) in toluene
at 90 °C for 6 h. We found that nano ZnAl2O4 gave better yield
compared to other catalysts (Table 1).
Due to the smaller surface area and lesser number of active
sites, bulk ZnAl2O4 showed poor yield. In order to optimize the
solvent system for the propargylamine synthesis using nano
ZnAl2O4, the reaction was carried out in various solvents including
water. It was found to end up with moderate yields. We observed
that under neat conditionsnano ZnAl2O4 resulted in 99.9% yield of
propargylamine (Table 2) (Scheme 1).
Fig. 5 Histogram of ZAO5
Table 1. Screening of the catalysts for one-pot synthesis of propargylamines
Entry
Catalyst
ZnO
Reaction time (h)
% Yield (a)
1
2
3
4
6
6
6
6
50
45
60
82
Al2O3
Bulk ZnAl2O4
Nano ZnAl2O4
Reaction conditions: Reactants: benzaldehyde (3 mmol), piperidine (3.3 mmol) and
phenylacetylene (3.6 mmol); solvent: 5 ml toluene, temperature: 90 °C, a GC
Table 2. Effect of solvents on the synthesis of propargylamines
Fig. 6 NH3-TPD (a) and CO2-TPD of ZAO5
Sl. No.
Solvent (5 ml)
Reaction time (h)
/Yield (%)a
4/82
1
2
3
4
5
6
Toluene
Ethanol
4/61
4/50
Tetrahyrofuran
Methanol
Acetonitrile
-
4/62
4/51
4/99.9
Reaction conditions: Reactants: benzaldehyde (3 mmol), piperidine (3.3 mmol) and
phenylacetylene (3.6 mmol), temperature: 90 °C, a GC
CHO
nano ZnAl2O4
+
+
90 0C, solvent free
N
R1
H
R1
3 mmol
3.6 mmol
3.3 mmol
Fig. 7 XPS spectrum of Cu/ZAO5
Scheme 1. Nano ZnAl2O4catalyzed synthesis of propargylamine derivatives under solvent
free conditions
4 | J. Name., 2012, 00, 1-3
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acetone to remove organic moieties and dried at 100 °C. We
This evidenced the efficiency of nano ZnAl2O4 under solvent free recycled the catalyst for 5 cycles without significant loss of activity
condition. Further, we explored the catalytic activity of nano (Fig. 8). Powder XRD pattern of nano ZnAl2O4, before and after
ZnAl2O4 for various benzaldehyde derivatives in order to reusability appeared to be the same indicating the reꢀexistence
understand the generality of the catalysts. We found 98ꢀ99.9% ofcatalyst without any change (Fig. 9a and 9b).
yield (Table 3).
We compared the activity of nano ZnAl2O4 with reported
catalysts for propargylamines synthesis (Table 4) and understood
The plausible mechanism for propargylamine synthesis using nano
ZnAl2O4 (Scheme 2)was proposed based on the literature reports. that most of the reported catalysts are expensive, require solvent
Iminium ion was formed from aldehyde and
and inert atmosphere and also need prolonged reaction time. Nano
ZnAl2O4 yielded high yield of propargylamine in lesser reaction
time under solvent free condition.
Table 3. One-pot synthesis of propargylamine derivativesusing nano ZnAl2O4
Sl. No.
R1
Reaction time
(h)/yield(a)
1
2
3
4
5
6
7
8
9
H
4/ 99.9
4/ 99
4 - CH3
4 - OCH3
4 - Cl
4/ 99
4/ 99.9
4/ 99
4 - F
2 - F
4.5/ 98
4.5/ 98
5/ 98
2 - MeO
2, 4 - Cl
3,4 - OCH3
5/98
Reactants: benzaldehyde (3 mmol), piperidine (3.3 mmol) and phenylacetylene (3.6
mmol), solvent free, temperature: 90 °C, aGC
Fig. 8 Reusability of ZAO5 for the synthesis of propargylamie
ZnAl2O4 nanoparticles
Scheme 2. Plausible mechanism for propargylamine synthesis using nano ZnAl2O4 under
solvent free conditions
piperidine at room temperature in the initial step. Due to the
presence of acidic and basic sites, catalyst nano ZnAl2O4 involved
in the activation of the C–H bond of acetylene forming ZnAl2O4–
acetylide intermediate in the second step. In the final step, iminium
ion reacted with ZnAl2O4–acetylide intermediate and resulted
propargylamine.
Fig. 9 Powder X-ray diffraction patterns of (a) fresh ZAO5 and (b) reused ZAO5
In order to reuse the catalyst, after every cycle the catalyst was
recovered by filtration using whatman filter paper, washed with
To understand the scope of the synthesized catalyst nano
ZnAl2O4 for three component coupling reaction, we tested the
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catalytic activity of nano ZnAl2O4 for the coupling reaction
Reusability of the catalyst was performed for the coupling
between benzaldehyde, 2ꢀaminopyridine and phenylacetylene. But between benzaldehyde, 2ꢀaminopyridine and phenylacetylene by
unfortunately no reaction took place (Table 5).
recovering the catalyst after every cycle. This was followed by
washing with acetone and drying under vacuum. After every cycle,
leaching of the metal ion was tested by AAS, and was found to be
nil. We successfully recycled the catalyst five times without
change in its activity (Fig. 10) and the catalyst was recovered
without any change (Figs. 11a and 11b).
The plausible mechanism for imidazo[1,2ꢀa]pyridines synthesis
using nano ZnAl2O4 (Scheme 4)was proposed on the basis of
literature reports. In the initial stage, imine was formed by the
condensation of 2ꢀaminopyridine with aldehydes. Formation of
propargylamine occurred due to the nucleophilic attack of alkyne
to imine. Due to the CꢀH activation of alkyl triple bond by copper
on ZnAl2O4,intramolecularnucleophilic attack of nitrogen in
pyridine ring to the triple bond either in 5ꢀexoꢀdig (Cꢀa attack) or
6ꢀendoꢀdig way (Cꢀb attack) took place. Which was later followed
by aromatic isomerization of the cyclic intermediate led to
Table 4. Comparison of the activity of the ZnAl2O4 with other catalysts for the synthesis of
propargylamines
Sl.
N
Catalyst
Solvent
Temperature/
reaction
Reaction Yield Referenc
time
(%)
e
o.
1
condition
NiCl2
CuI
Toluene
PEG
110 °C/Argon
8 h
95
87
10 (i)
2
100
12 h
10 (h)
°C/Nitrogen
110 °C
3
4
5
SiO2@Cu
InCl3
Toluene
Toluene
Toluene
5 h
94
90
98
23
10 (f)
18
120 °C/Argon
100 °C
20 h
15 h
*NAP-
Mg-
Au(0)
Nano
Co3O4
Nano
ZnAl2O4
6
7
Toluene
-
130 °C
90 °C
15 h
4 h
87
26
imidazo[1,2ꢀa]pyridines.
R
N
99.9
present
work
CHO
N
nano copper/ nano ZnAl2O4
90 0C, solvent free, N2 atm.
CH2
* Nano Active Magnesium Oxide Plus
N
NH2
R
3 mmol
3 mmol
3 mmol
Reactants: benzaldehyde piperidine, phenylacetylene
Table 5 Comparison of the activity of the catalysts for imidazo[1,2-a]pyridine
Scheme 3 Cu/nano ZnAl2O4catalyzed synthesis of imidazo[1,2-a]pyridine derivatives under
solvent free condition
Sl. No.
catalyst
ZnAl2O4
CuO
Yield (%)a
Table 6. One-pot synthesis of imidazo[1,2-a]pyridine derivatives
1
2
3
4
nil
61
69
90
Sl. No.
R1
Reaction time (h)/yield(a)
Cu powder
1
2
3
4
5
6
H
6/ 90
4/ 89
4/ 89
4/ 94
4/ 94
4.3/ 90
8 wt% Cu/ nano
ZnAl2O4
4 - CH3
4 - OCH3
4 - Cl
5
6
8 wt% Ni/ nano
ZnAl2O4
51
55
4 - F
8% Cu-Ni/ nano
ZnAl2O4
2 - F
Reactants: Aldehyde (3 mmol), 2-aminopyridine (3 mmol) and phenylacetylene (3
mmol), solvent free, N2 atmosphere, temperature: 90 °C, aGC
Reactants: benzaldehyde (3 mmol), 2-aminopyridine (3 mmol) and phenylacetylene (3
mmol), solvent free, N2 atmosphere, temperature: 90 °C, aGC
Understanding the need of copper and other transition metal
catalysts for this reaction, we explored the catalytic activity of
various catalysts such as CuO, Cu powder, 8 wt% Cu/ nano
ZnAl2O4, 8 wt% Ni/ nano ZnAl2O4 and 8% CuꢀNi/ nano ZnAl2O4
under solventꢀfree condition as well as with solvent. The catalysts
Ni/nano ZnAl2O4 and CuꢀNi/ nano ZnAl2O4 resulted in moderate
yields, whereas, 8 wt% Cu/ nano ZnAl2O4 resulted in better yields
under solventꢀfree and in the presence of N2 atmosphere (Scheme
3). Hence, it was evident that the active site for imidazo[1,2ꢀ
a]pyridine synthesis was copper and that nano ZnAl2O4 acted as
support for copper nanoparticles because it provided large surface
area and also aggregation of the copper nanoparticles was reduced.
We carried out the reaction for other benzaldehyde derivative and
94ꢀ89% yields were achieved in 4ꢀ6h(Table 6).
Fig. 10 Reusability of ZAO5 for the synthesis of imidazo[1,2-a]pyridines
6 | J. Name., 2012, 00, 1-3
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Table 7. Comparison of the activity of the Cu/ZnAl2O4 with other catalysts for the synthesis
of propargylamines
Sl.
Catalyst
Solvent
Toluene
Temperatur
e/reaction
condition
120°C/
Reac
tion
Yield Referenc
No.
(%)
e
time
16 h
1
CuCl +
Cu(OTf)2
InBr3
93
28
Nitrogen
Reflux/ Et3N
60 °C
2
3
4
Toluene
Water
12 h
6 h
82
85
60
30
32
34
Iodine
CuSO4/
TSOH
Toluene
110 °C
18 h
5
Cu/nano
ZnAl2O4
-
90 °C
6 h
90
Present
work
Reactants: Benzaldehyde, 2-aminopyridine and phenylacetylene
EXPERIMENTAL
Materials
Zn(NO3)2.6H2O, Al(NO3)3.9H2O and ethanolamine were
purchased from Himedia. Organic chemicals were purchased from
Sigma Aldrich. All the chemicals were of high purity and used
without further purification.
Fig. 11 Powder X-ray diffraction patterns of (a) fresh Cu/ZAO5 and (b) reused Cu/ZAO5
Synthesis of ZnAl2O4 nanoparticles
In a typical synthesis, the aqueous solutions of Zinc nitrate (1 M)
and Aluminium nitrate (2 M) were mixed under vigorous stirring.
The above homogeneous solution was stirred for 2 h followed by
the addition of aqueous solution of ethanolamine (ethanolamine to
water volume ratio of 6: 4) drop wise until the white precipitation
stopped. The white precipitate was collected by filtration, washed
with double distilled water, followed by acetone and it was then
dried in oven at 80 °C overnight. The dried precursor was calcined
at 300 °C, 500 °C and 700 °C with intermittent grinding.
Synthesis of copper supported on ZnAl2O4 nanoparticles
The above synthesized nano ZnAl2O4 was dispersed in known
amount of copper nitrate solution under vigorous stirring. The
stirring was continued for 6 h followed by filtration. The
precipitate was washed with water to remove excess of copper
nitrate, and was dried with acetone. The above precipitate was
dispersed in water using ultrasonication and the dispersion was
heated at 60 °C ꢀ 70 °C on hot plate under nitrogen atmosphere. To
this dispersion, 2 ml of hydrazine hydrate was added drop wise
under vigorous stirring under nitrogen atmosphere. Stirring was
continued for 2 h. The obtained precipitate was collected by
filtration followed by vacuum drying.
Scheme 4. Plausible mechanism for the synthesis of imidazo[1,2-a]pyridine using Cu/nano
ZnAl2O4 under solvent free conditions
We compared the activity of Cu/nano ZnAl2O4 with reported
catalysts for imidazo[1,2ꢀa]pyridinessynthesis (Table 7). Most of
the reported catalysts are expensive, require additive and need
prolonged reaction time. Cu/ nano ZnAl2O4 provided good yield of
imidazo[1,2ꢀa]pyridinesin lesser reaction time under solvent free
condition.
General synthetic procedure for ZnAl2O4 nanoparticles catalyzed
propargylamines
Aldehyde (3 mmol), piperidine (3.3 mmol) and phenyl acetylene
(3.6 mmol) were placed in round bottom flask along with nano
ZnAl2O4 and stirred at 80 °C without solvent. The reaction was
monitored by TLC. After completion, the reaction mixture was
cooled and extracted with DCM solvent.
General synthetic procedure for Cu/ nano ZnAl2O4 catalyzed
imidazo[1,2-a]pyridines
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Aldehyde (3 mmol), 2ꢀaminopyridine (3 mmol) and phenyl
acetylene (3 mmol) were placed in round bottom flask along with
Cu/nano ZnAl2O4. Nitrogen atmosphere was created in round
bottom flask and the mixture was stirredat 80 °C without solvent
under. The reaction was monitored by TLC. The reaction mixture
was cooled and extracted with DCM solvent.
Acknowledgement
Triveni Rajashekhar Mandlimath thanks CSIR for providing
Senior Research Fellowship. She also thanks B. Uma Mahesh and
M. Sathish Kumar for their valuable suggestions. The DSTꢀFIST
NMR facility at VIT University is greatly acknowledged (GCꢀ
MS). Authors thank Dr.R.Srinivasan, SSL, VIT for language
editing.
Characterization
Phase purity of the synthesized catalysts was determined by
powder Xꢀray diffraction (XRD) patterns on Bruker Xꢀray
diffractometer (D8 Advanced) with Cu Kα radiation (λ = 1.5406
Å) in the angle range of 2θ = 10 °ꢀ70 ° at room temperature.
Specific surface area of the catalysts were measured from Nitrogen
adsorption desorption isotherms on Micromeritics ASAP 2020
V3.00 H by BrunauerꢀEmmettꢀTeller (BET) method. Scanning
Electron Microscopic (SEM) images and Energy Dispersive Xꢀray
Analysis (EDX) data were obtained on JEOL JSM 7001F with
BRUKERꢀ QUNTAX Version 1.8.2. Morphology and crystallite
size of the catalysts were determined by Transmission Electron
microscopic (TEM) on JEOL 3010 instrument with UHR pole
piece. Surface acidity of the synthesized nano ZnAl2O4 was
analyzed by NH3 temperatureꢀprogrammed desorption (TPD)
technique on Autochem 2910, Micromeritics instrument. 1.0 g of
nano ZnAl2O4 was preheated in 30 mL high pure Helium flow at
120 ºC for 30 min at the heating rate of 10 ºC/min. Adsorption of
NH3 was done by passing 10% NH3 in Helium gas at 30 mL/min
flow through the sample for 30 min followed by purging pure
Helium at 30 mL/min. NH3 desorption was studied from 100 ºC to
650 ºC at 10 ºC/min utilizing thermal conductivity detector. CO2
temperatureꢀprogrammed desorption, TPD technique on the same
instrument was used for analyzing surface basicity of nano
ZnAl2O4. In a typical procedure, dried nano ZnAl2O4 powder (1.0
g) was pretreated in 50 mL high pure Helium flow at 200 ºC for 30
min. After which, the sample was saturated by CO2 by passing
10% CO2 in Helium gas with a flow rate of 75 mL/min at 30 ºC.
The physisorbed CO2 was removed by flushing Helium at 105 ºC
over the sample for 2 h. TPD analysis was carried out from 100 ºC
to 750 ºC at the heating rate of 10 ºC/min. XPS analysis of
Cu/ZAO5 was performed on XM1000 spectrometer at room
temperature with Al K radiation (h = 1486.6 eV) as the excitation
source. C 1s 284.6 eV signal was referenced for the binding energy
values. Concentration of leached metal ions of the catalyst after
every cycle of the reaction was tested by Atomic Absorption
Spectroscopic technique using Varian AA240 instrument. Organic
compounds were confirmed by GCꢀMS.
Notes and references
*Chemistry Division – School of Advanced Sciences
VIT University, Vellore – 632014, Tamil Nadu, India
Fax:
+914162243092;
Tel:
+914162244520;
Eꢀ
mail:sathiya_kuna@hotmail.com
S: Supporting Information
1
(a) E. Vedejs, J. W. Grissom, J. K. Preston, J. Org. Chem., 1987,
52 3488-3489. (b) N. Gommermann, P. Knochel, Chem.
Commun., 2004, 20, 2324-2325. (c) Q. Xu, E. Rozners, Org. Lett.,
2005, , 2821-2824.
(a) F. Xiao, Y. Chen, Y. Liu, J. Wang, Tetrahedron, 2008, 64, 2755-
2761. (b) B. Yan, Y. Liu, Org. Lett., 2007, , 4321-4326. (c) E. S.
,
7
2
9
Lee, H. S. Yeom, J. H. Hwang, S. Shin, Eur. J. Org. Chem., 2007,
2007, 3503-3507. (d) Y. Yamamoto, H. Hayashi, T. Saigoku, H.
Nishiyama, J. Am. Chem. Soc., 2005, 127, 10804-10805. (e) D. F.
Harvey, D. M. Sigano, J. Org. Chem., 1996, 61, 2268-2272.
3
4
(a). A. Jenmalm, W. Berts, Y. L. Li, K. Luthman, I. C. Bregh, U.
Hacksell, J. Org. Chem., 1994, 59, 1139-1148. (b) Y. Imada, M.
Yuasa, I. Nakamura, S. I. Murahashi, J. Org. Chem., 1994, 59
,
2282-2284. (c) M. Miura, M. Enna, K. Okuro, M. Nomura, J. Org.
Chem., 1995, 60, 4999-5004. (d) Trybulski, J. Eugene, Brabander,
J. Herbert, 1994, US5346910.
(a) C. Binda, F. Hubalek, M. Li, Y. Herzig, J. Sterling, D. E.
Edmondson, A. Mattevi, J. Med. Chem., 2004, 47, 1767-1774. (b)
C. W. Olanow, Neurology, 2006, 66, S69-S79. (c) M. Y. Falach, T.
Amit, O. B. Am, M. B. H. Youdim, FASEB J., 2003, 17, 2325- 2342.
V. Oldfield, G. M. Keating, C. M. Perry, Drugs, 2007, 67, 1725-
1747.
(a) M. Lhassani, O. Chavignon, J. M. Chezal, J. C. Teulade, J. P.
Chapat, R. Snoeck, G. Andrei, J. Balzarini, E. D. Clercq, A.
Gueiffier, Eur. J. Med. Chem., 1999, 34, 271-274. (b) K. C. Rupert,
J. R. Henry, J. H. Dodd, S. A. Wadsworth, D. E. Cavender, G. C.
Olini, B. Fahmy, J. J. Siekierka, Bioorg. Med. Chem. Lett., 2003,
13, 347-350. (c) L. Almirante, L. Polo, A. Mugnaini, E. Provinciali,
P. Rugarli, A. Biancotti, A. Gamba, W. Murmann, J. Med. Chem.,
5
6
1965, 8, 305-312. (d) Y. Kastura, S. Nishino, Y. Inoue, M. Tomoi,
H. Takasugi, Chem. Pharm. Bull., 1992, 40, 371-380. (e) Y. Rival,
G. Grassy, G. Michel, Chem. Pharm. Bull., 1992, 40, 1170 - 1176.
(a) A. N. Jain, J. Med. Chem., 2004, 47, 947-961. (b) N. Hsu, S. K.
Jha, T. Coleman, M. G. Frank, Behav. Brain Res., 2009, 201, 233-
236. (c) G. Trapani, M. Franco, L. Ricciardi, A. Latrofa, G. Genchi,
E. Sanna, F. Tuveri, E. Cagetti, G. Biggio, G. Liso, J. Med. Chem.,
1997, 40, 3109-3118. (d) S. M. Hanson, E. V. Morlock, K. A.
Satyshur, C. Czajkowski, J. Med. Chem., 2008, 51, 7243-7252.
S. Takizawa, J. I. Nishida, T. Tsuzuki, S. Tokito, Y. Yamashita,
Chem. Lett., 2005, 34, 1222-1223; b) S. Takizawa, J. I. Nishida, Y.
Yamashita, T. Tsuzuki, S. Tokito, Mol. Cryst. Liq. Cryst., 2006,
455, 381-385; c) S. Takizawa, J. I. Nishida, T. Tsuzuki, S. Tokito, Y.
Yamashita, Inorg. Chem., 2007, 46, 4308- 4319.
7
Conclusion
8
9
In summary, we developed a facile, simple and efficient method
for the synthesis of porous nano ZnAl2O4 with large surface area.
The exploration of nano ZnAl2O4 and Cu/ nano ZnAl2O4 was
found to be efficient catalysts for the synthesis of propargylamines
and imidazo[1,2ꢀa]pyridines respectively. The current protocols
were simple, solventꢀ free, and they did not require any additive.
Being cheap and reusable, nano ZnAl2O4 was found to be superior
to the existing homogeneous and expensive noble metal catalysts.
(a) M. E. Jung, A. Huang, Org. Lett., 2000,
Patil, S. V. Patil, V. D. Bobade, Syn. Lett., 2011,
W. Ryan, C. Ainsworth, J. Org. Chem., 1961, 26, 1547-1550. (d)
T. Takahashi, F. Bao, G. Gao, M. Ogasawara, Org. Lett., 2003,
2
, 2659-2661, (b) S. S.
8, 1157-1159. (c)
5
,
3479-3481. (e) T. Harada, T. Fujiwara, K. Iwazaki, A. Oku, Org.
8 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 9 of 10
Journal Name
Lett., 2000,
View Article Online
DOI: 10.1039/C5RA20812B
ARTICLE
2
, 1855-1857, (f) A. Tuulmets, V. Pallin, J. T. Taul, P.
36 T. R. Mandlimath, B. Umamahesh, K. I. Sathiyanarayanan, J. Mol.
Catal. A: Chem., 2014, 391, 198-207.
37 B. Umamahesh, T. R. Mandlimath, K. I. Sathiyanarayanan, RSC
Burk, K. Raie, J. Phys. Org. Chem., 2002, 15, 701-705.
10 (a) E. Ramu, R. Varala, N. Sreelatha, S. R. Adapa, Tetrahedron
Lett., 2007, 48, 7184-7190. (b) C. Wei, Z. Li, C. J. Li, Org. Lett.,
Adv., 2014, 5, 6578-6587.
2003,
5
, 4473-4475. (c) C. Wei, C. J. Li, J. Am. Chem. Soc., 2003,
38 Q. Liu, L. Wang, C. Wang, W. Qu, Z. Tian, H. Ma, D. Wang, B.
Wang, Z. Xu, Appl. Catal., B, 2013, 136-137, 210-217.
39 S. Velu, K. Suzuki, Chinnakonda, S. Gopinath, H. Yoshida, T.
125, 9584-9585. (d) W. W. Chen, R. V. Nguyen, C. J. Li,
Tetrahedron Lett., 2009, 50, 2895-2898, (e) D. S. Raghuvanshi, K.
N. Singh, Syn. Lett., 2011,
3
, 373-377. (f) Y. Zhang, P. Li, M.
Hatoor, Phys. Chem. Chem. Phys., 2002, 4, 1990-1999.
Wang, L. Wang, J. Org. Chem., 2009, 74, 4364-4367. (g) J. S.
Yadav, B. V. S. Reddy, A. V. H. Gopal, K. S. Patil, Tetrahedron
Lett., 2009, 50, 3493-3496. (h) Q. Zhang, J. X. Chen, W. X. Gao, J.
C. Ding, H. Y. Wu, Appl. Organometal. Chem., 2010, 24, 809-812.
(i) S. Samai, G. C. Nandi, M. S. Singh, Tetrahedron Lett., 2010, 51
5555-5558. (j) Li, P. Hua, Wang, Lei, Chin. J. Chem., 2005, 23
1076-1080.
,
,
11 (a) K. K. Y. Kung, V. K. Y. Lo, H. M. Ko, G. L. Li, P. Y. Chan, K. C.
Leung, Z. Zhou, M. Z. Wang, C. M. Che, M. K. Wonga, Adv. Synth.
Catal.,2013, 355, 2055-2070. (b) V. K. Y. Lo, K. K. Y. Kung, M. K.
Wong, C. M. Che, J. Organometal. Chem., 2009, 694, 583-591.
(c) V. K. Y. Lo, Y. Liu, M. K. Wong, C. M. Che, Org. Lett., 2006,
1529-1532. (d) G. Villaverde, A. Corma, M. Iglesias, F. Sánchez,
ACS Catal., 2012, , 399-406.
8,
2
12 Y. Zhang, A. M. Santos, E. Herdtweck, J. Minkbc, F. E. Kuhn, New
J. Chem., 2005, 29, 366-370.
13 (a) M. Kidwai, V. Bansal, A. Kumar, S. Mozumdar, Green Chem.,
2007, 9, 742-745. (b) W. Yan, R. Wang, Z. Xu, J. Xu, L. Lin, Z.
Shen, Y. Zhoua, J. Molecul. Catal. A: Chem., 2006, 255, 81-85.
14 X. Zhang, A. Corma, Angew. Chem. Int. Ed., 2008, 47, 4358-4361.
15 B. J. Borah, S. J. Borah, K. Saikia, D. K. Dutta, Catal. Sci. Technol.,
2014, 4, 4001-4009.
16 R. Mallampati, S. Valiyaveettil, ACS Sustain. Chem. Eng., 2014, 2,
855-859.
17 F. Movahedi, H. Masrouri, M. Z. Kassaee, J. Molecul. Catal. A:
Chem., 2014, 395, 52-57.
18 K. Layek, R. Chakravarti, M. L. Kantam, H. Maheswarana, A.
Vinu, Green Chem., 2011, 13, 2878-2887.
19 P. Li, L. Wang, Y. Zhang, M. Wang, Tetrahedron Lett.,2008, 49,
6650-6654.
20 L. Abahmane, J. M. Kçhler, G. A. Grob, Chem. Eur. J., 2011, 17
3005-3010.
,
21 B. J. Borah, S. J. Borah, L. Saikia, D. K. Dutta, Catal. Sci. Technol.,
2014, , 1047-1054.
4
22 J. S. Yadav, B. V. S. Reddy, C. S. Reddy, K. Rajasekhar, J. Org.
Chem., 2003, 68, 2525-2527.
23 H. Guo, X. Liu, Q. Xie, L. Wang, D. L. Peng, P. S. Branco, M. B.
Gawande, RSC Adv., 2013, 3, 19812-19815.
24 M. K. Patil, M. Keller, B. M. Reddy, P. Pale, J. Sommer, Eur. J.
Org. Chem., 2008, 2008, 4440-4445.
25 C. Mukhopadhyay, S. Rana, Catal. Comm., 2009, 11, 285-289.
26 K. D. Bhatte, D. N. Sawant, K. M. Deshmukh, B. M. Bhanage,
Catal. Comm., 2011, 16, 114-119.
27 J. Dulle, K. Thirunavukkarasu, M. C. M. Hazeleger, D. V.
Andreeva, N. R. Shiju, G. Rothenberg, Green Chem., 2013, 15
1238-1243.
,
28 I. Luz, F. X. L. Xamena, A. Corma, J. Catal., 2012, 285, 285-291.
29 N. Chernyak, V. Gevorgyan, Angew. Chem. Int. Ed., 2010, 49
2743-2746.
,
30 B.V. S. Reddy, P. S. Reddy, Y. J. Reddy, J. S. Yadav, Tetrahedron
Lett.,2011, 52, 5789–5793.
31 S. K. Guchhait, A. L. Chandgude, G. Priyadarshani, J. Org. Chem.,
2012, 77, 4438-4444.
32 I. R. Siddiqui, P. Rai, Rahila, A. Srivastava, S. Shamim,
Tetrahedron Lett., 2014, 55, 1159-1163.
33 S. Mishra, R. Ghosh, Synthesis, 2011, 21, 3463-3470.
34 P. Liu, L. Fang, X. Lei, G. Lin, Tetrahedron Lett., 2010, 51, 4605-
4608.
35 P. Liu, C. L. Deng, X. Lei, G. Lin, Eur. J. Org. Chem., 2011, 7308-
7316.
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