Doping of copper (I) oxide onto a solid support as a recyclable catalyst for acetylation of amines/alcohols/phenols and synthesis of trisubstituted imidazole

Article abstract of DOI:10.1007/s13738-015-0730-9

A study of copper-mediated C-heteroatom especially C-N and C-O bond formations using simpler methodologies has been carried out. In the present work, acetylation of various substrates such as amines, phenols and alcohols; synthesis of 2,4,5-trisubstituted imidazole is done using simple and easily available starting materials. Copper (I) oxide was synthesized in situ by the reduction of Fehling's solution with glucose followed by its anchoring onto different supports like silica, HAP, basic alumina and cellulose. Comparison and contrasts between the reactivity of copper (I) oxide supported onto different supports for these reactions are made. The reactivity of copper (I) oxide seems to be largely dependent on the nature of support and the most active catalyst for a particular reaction was further characterized by different spectroscopic techniques such as FTIR, XRD, TGA, XPS, SEM, TEM and AAS. The catalysts were found to be stable, easily recyclable without any significant loss in activity. Graphical abstract: Applications of solid supported copper (I) oxides (where solid support is silica, HAP, cellulose and basic alumina) are studied for various organic transformations with special emphasis on C-N and C-O bond formation reactions.[Figure not available: see fulltext.]

Full text of DOI:10.1007/s13738-015-0730-9

J IRAN CHEM SOC
DOI 10.1007/s13738-015-0730-9
ORIGINAL PAPER
Doping of copper (I) oxide onto a solid support as a recyclable
catalyst for acetylation of amines/alcohols/phenols and synthesis
of trisubstituted imidazole
Manjulla Gupta1 · Monika Gupta1
Received: 9 April 2015 / Accepted: 29 August 2015
© Iranian Chemical Society 2015
Abstract A study of copper-mediated C–heteroatom
especially C–N and C–O bond formations using simpler
methodologies has been carried out. In the present work,
acetylation of various substrates such as amines, phenols
and alcohols; synthesis of 2,4,5-trisubstituted imidazole is
done using simple and easily available starting materials.
Copper (I) oxide was synthesized in situ by the reduction of
Fehling’s solution with glucose followed by its anchoring
onto different supports like silica, HAP, basic alumina and
cellulose. Comparison and contrasts between the reactivity
of copper (I) oxide supported onto different supports for
these reactions are made. The reactivity of copper (I) oxide
seems to be largely dependent on the nature of support and
the most active catalyst for a particular reaction was further
characterized by different spectroscopic techniques such as
FTIR, XRD, TGA, XPS, SEM, TEM and AAS. The cata-
lysts were found to be stable, easily recyclable without any
significant loss in activity.
Graphical abstract Applications of solid supported cop-
per (I) oxides (where solid support is silica, HAP, cellulose
and basic alumina) are studied for various organic transfor-
mations with special emphasis on C–N and C–O bond for-
mation reactions.
Keywords Acetylation · Amines · C–heteroatom ·
Spectroscopic techniques · Recyclability
Introduction
The backbone of many organic compounds is composed of
carbon–carbon bonds, but these molecules becomes func-
tional only in the presence of heteroatoms, such as nitro-
gen, oxygen and sulphur, which are held in these molecules
by C–heteroatom bonds, e.g. in many pharmaceuticals and
conductive polymers. Heterocyclic compounds in which
C–N, C–O or C–S bonds are present in the ring structure
are found in all applications of chemistry [1]. The develop-
ment of synthetic approaches to organic compounds with
Csp2–C and Csp2–heteroatom bonds catalysed by transition
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-015-0730-9) contains supplementary
material, which is available to authorized users.
* Monika Gupta
monika.gupta77@rediffmail.com
1
Department of Chemistry, University of Jammu,
Jammu 180 006, India
1 3

J IRAN CHEM SOC
NHCOCH3
NH2
metals is of great interest to organic chemists [2]. According
to Buchwald and Hartwig, the formation of Csp2–N bonds
gains special attention [3–10]. These reactions require harsh
conditions such as strong bases, high boiling point solvents
and are catalysed by palladium [3–10] or nickel [8–10]
complexes. Transition metals supported on solid phase as
catalyst are of prime importance due to their advantages
as they are more selective, stable at high temperature, eas-
ily separated from the reaction mixture at the end of the
process, and can be reused. However, the use of solid sup-
ported transition metal catalysts [11–13] is often described
as ‘solid-state chemistry’ [2]. Although C–heteroatom bond
formation reactions using palladium, ruthenium, iridium,
and platinum catalysts have been explored, copper‐cata-
lysed C–heteroatom bond formation has gained more atten-
tion because of its low cost, non‐toxic nature, and excellent
selectivity [14]. Cuprous oxide (Cu2O) which is a p-type
semiconductor recently attracted much attention due to its
potential applications in various fields such as solar cells
[15], pigments [16], catalysts, and photocatalysts [17]. Vari-
ous methods have reported for the synthesis of Cu2O [18–
20]. Cuprous oxide has been supported on various supports
such as cuprous oxide on charcoal [21], CuI-zeolites [22],
cuprous oxide nanoparticles dispersed on reduced graphene
oxide (RGO) [23], copper catalysts supported on TiO2–
ZrO2 [24], PVA-stabilized Cu2O particles [25], CuO/SiO2
[26], cuprous oxide nanoparticles/graphene composite [27],
etc. Moreover, heterogeneously supported copper catalyst
catalyses many industrially important reactions.
HAP-Cu2O
+
CH3COCl
CH3CN, 50 oC
R
R
Scheme 1 N-Acetylation of amines catalysed by HAP–Cu2O in ace-
tonitrile at 50 °C
HAP-Cu2O
+
ROH / ArOH
ROCOCH3 / ArOCOCH3
CH3COCl
CH3CN, 50 oC
Scheme 2 O-Acetylation of alcohols and phenols catalysed by
HAP–Cu2O in acetonitrile at 50 °C
In view of the above-mentioned importance of these
reactions, we have been encouraged to develop a sim-
ple, mild and efficient methodology for the N- as well
as O-acetylation of amines (Schemes 1, 2), phenols and
alcohols; synthesis of 2,4,5-trisubstituted imidazole
(Scheme 3). In continuation of our ongoing research on the
applications of solid supported copper (I) oxide [14, 53]
as heterogenous and recyclable catalyst in organic synthe-
sis, we have reported a clean, mild and simple procedure
for the N- as well as O-acetylation of amines, phenols and
alcohols; synthesis of 2,4,5-trisubstituted imidazole.
The acetylation of amines, alcohols and phenols is a
common and inexpensive means to protect, identify and
characterize these functionalities in a multi-step synthetic
process [28, 29]. Acetic anhydride and acetyl chloride are
generally used in the presence of acidic or basic catalysts
in an organic medium [30]. Acetyl chloride is one of the
most commonly available and cheap acylating agent, but it
is highly reactive and unstable in aqueous medium. For this
organic transformation, a large number of homogenous as
well as heterogenous catalysts have been reported [31–49].
But these reported catalysts suffer from some drawbacks
such as long reaction times drastic reaction conditions,
tedious workup and moreover, the catalysts are moisture
sensitive or expensive [50].
Multi-component reactions (MCRs) have proved to be
remarkably successful in generating products in a single
synthetic operation. The development of new MCRs and
improvement of known multi-component reactions are an
area of considerable interest. One such reaction is the syn-
thesis of imidazoles [51]. Multi substituted imidazole and
derivatives are an important class of compounds in the field
of medicinal chemistry. The use of substituted imidazoles
as Ionic Liquids provides a new approach to Green Chem-
istry [52].
Experimental
Materials and instrumentation
Silica gel was purchased from ACROSS organics and all
other chemicals were purchased from Merck and Sigma
Aldrich and were used without further purification. IR
spectra of the catalyst and the synthesized compounds were
recorded in the range of 4000–300 cm−1 on a Shimadzu
Prestige-21 spectrophotometer. TGA of the catalyst was
obtained on a Linesis Thermal Analyser. X-ray diffracto-
grams were recorded in 2-h range of 10–80 on a Panalyti-
cals X’pert Pro X-ray diffraction spectrometer using CuKα
radiation. XPS spectra of the catalyst were recorded on
KRATOS ESCA model AXIS 165 (Resolution). SEM was
recorded on JSM-7600F and TEM was recorded on Hitachi
(H-7500) 120 kV with CCD camera. The atomic absorp-
tion spectrometric analysis (AAS) was done on Avanta-M
atomic absorption spectrometer. H NMR and 13C NMR
of the compounds were obtained on Bruker Avance III
(400 MHz) spectrometer. Mass spectra of the products were
obtained on a Bruker Daltonics Esquire 3000 spectrometer.
1
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J IRAN CHEM SOC
Scheme 3 Synthesis of
2,4,5-trisubstituted imidazole
catalysed by SiO2–Cu2O in
ethanol at 80 °C
CHO
R
O
O
N
SiO2-Cu2O
+
+
NH4OAc
ethanol
80 oC
N
H
R
Preparation of solid supported copper (I) oxide
[solid–Cu2O]
General procedure for synthesis of 2,4,5‑trisubstituted
imidazole using SiO2–Cu2O
To a round-bottom flask containing solid support (10 g),
Fehling’s solution (50 mL) was added and the reaction
mixture was stirred at 100 °C. After every interval of
30 min, 2 mL of glucose solution (0.5 g in 96 mL of water)
was added for a total of 24 h. Then the catalyst was fil-
tered, washed with water till washings were colourless and
dried in an oven at 110 °C. In order to remove extra glu-
cose, the catalyst was refluxed in water at 120 °C for 6 h
(3 × 2 h). Finally, the catalyst was dried at 110 °C for 5 h
in an oven.
In rounded-bottom flask, benzil (1 mmol), aldehyde
(1 mmol), and ammonium acetate (4 mmol) in ethanol
were added to SiO2–Cu2O (0.2 g) and the reaction mix-
ture was heated to 80 °C for the required period of time
After completion of the reaction which was monitored by
TLC, the reaction mixture was cooled to room temperature
and filtered. The residue was washed with water followed
by EtOAc (3 × 10 mL). The product was obtained after
the removal of solvent under reduced pressure followed by
crystallization from pet ether or EtOAc:pet ether or pass-
ing through column of silica and elution with EtOAc:pet
ether.
General procedure for N‑acetylation of amines using
HAP–Cu2O
To a mixture of amine (1 mmol), acetyl chloride (1 mmol)
in acetonitrile (5 mL) were added hydroxyapatite –Cu2O
(0.1 g) under air atmosphere. The reaction mixture was
refluxed at 50 °C for an appropriate time. The progress of
the reaction was monitored through TLC. Upon comple-
tion of the reaction, the reaction mixture was cooled to
room temperature and filtered. The residue was washed
with water followed by EtOAc (3 × 10 mL). The product
was obtained after the removal of solvent under reduced
pressure followed by crystallization from pet ether or
EtOAc:pet ether or passing through column of silica and
elution with EtOAc:pet ether.
Results and discussion
Preparation and characterization of catalyst
All the supported copper (I) catalysts such as SiO2–Cu2O
(I), hydroxyapatite–Cu2O (II), basic Al2O3–Cu2O (III) and
cellulose–Cu2O (IV) have been prepared according to ear-
lier reported procedure [14].
All the above reported catalysts have been tested for
N-acetylation of amines, O-acetylation of phenols and
alcohols and synthesis of 2,4,5-trisubstituted imidazole.
It was found that hydroxyapatite-supported copper (I)
oxide proved very efficient to catalyse the acetylation of
amines, phenols/alcohols, whereas SiO2–Cu2O was found
to be active to catalyse the 2,4,5-trisubstituted imidazole
(Table 1).
General procedure for O‑acetylation of alcohols
and phenols using HAP–Cu2O
A mixture of alcohol or phenol (1 mmol), acetyl chloride
(1 mmol), hydroxyapatite –Cu2O (0.1 g) in acetonitrile
was taken in a round-bottom flask and stirred at 50 °C for
an appropriate time. On completion (monitored by TLC),
the reaction mixture was cooled to room temperature and
filtered. The residue was washed with water followed by
EtOAc (3 × 10 mL). The product was obtained after the
removal of solvent under reduced pressure followed by
crystallization from pet ether or EtOAc:pet ether or pass-
ing through column of silica and elution with EtOAc:pet
ether.
Further, hydroxyapatite-supported copper (I) oxide was
characterized by various spectroscopic techniques such as
FTIR, thermogravimetric analysis (TGA), X-ray diffrac-
tometry (XRD), X-ray photoelectron spectroscopy (XPS),
scanning electron microscopy (SEM), transmission elec-
tron microscopy (TEM) and atomic absorption spectro-
scopic analysis (AAS). In the FTIR spectra, the catalyst
showed strong absorption peaks at 472, 570, 601, 631, 963,
1410, 1454, 1992, 2076, 2143, 2903, 3571 cm−1 in addi-
tion to broad peaks at 1051 and 1091 cm−1 (Fig. 1). The
peak at 3571 cm−1 confirms the presence of OH group. In
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J IRAN CHEM SOC
B.Al2O3–Cu2O
Table 1 Comparison of the reactivity of different solid supported copper (I) oxides
S. no. Name of the reaction SiO2–Cu2O HAP–Cu2O
Cellulose–Cu2O
Time (min) Yieldd (%) Time (min) Yieldd (%) Time (min) Yieldd (%) Time (min) Yieldd (%)
1
2
N-Acetylation of aminesa
12
10
85
90
5
5
95
93
13
20
82
80
20
30
75
78
O-Acetylation of phenols and
alcoholsb
3
Synthesis of 2,4,5-trisubstituted
imidazolec
15
90
60
75
60
50
60
30
Optimized reaction conditions: a p-nitroaniline (1 mmol), acetyl chloride (1 mmol), solid supported copper (I) oxide (0.1 g), acetonitrile (5 mL)
at 50 °C
b
p-Nitrobenzylalcohol (1 mmol), acetyl chloride (1 mmol), solid supported copper (I) oxide (0.1 g), acetonitrile (5 mL) at 50 °C
c
Benzil (1 mmol), benzaldehyde (1 mmol), ammonium acetate (4 mmol), solid supported copper (I) oxide (0.2 g), ethanol (5 mL) at 80 °C
d
Yields refer to separation through column chromatography or through crystallization
Fig. 1 FTIR of HAP–Cu2O
view of the references papers [54–56], it can be concluded
that the peak at 631 cm−1 corresponds to the IR absorption
band due to copper (I) oxide.
in HAP–Cu2O which overruled the possibility of formation
of CuO.
The amount of copper loaded onto HAP–Cu2O was
determined through AAS analysis. It was found that HAP–
Cu2O contained 0.0162 g of copper per gram of catalyst.
The oxidation state of copper in HAP–Cu2O is deter-
mined by the measurements of binding energies using XPS
(Fig. 4). The spectrum of Cu2p3/2 photoelectrons showed
a strong peak at 933.6 eV which confirms the presence of
copper (I) in HAP–Cu2O.
The SEM and TEM images reflect the morphology and
microstructure of the catalyst. The SEM images revealed
that the catalyst is a fine homogenous structure with porous
structure and it was observed that copper oxide particles
are adsorbed onto the surface of HAP (Fig. 5).
The stability of HAP–Cu2O was determined using
thermogravimetric analysis (Fig. 2) and it has been
inferred from the figure that the catalyst showed initial
weight loss of 3.27 % at 110.9 °C which may be due to
the loss of residual water trapped onto the catalyst. Fur-
ther, the catalyst showed no significant weight loss up to
470 °C and after. Hence, the catalyst, i.e. HAP–Cu2O is
stable up to 470 °C and it is safe to carry out the reaction
at 80 °C.
The XRD pattern of HAP–Cu2O showed peaks that were
indexed on the basis of crystallographic data for the known
structure of HAP (Fig. 3). In addition, reflection patterns at
2θ = 35.5° and 42.1° attributed to copper (I) oxide. Similar
to SiO2–Cu2O [14], there is no peak at 2θ = 38.7° present
The TEM micrographs showed the uniform distribution
of copper onto HAP with a mean diameter of 3 nm. It can
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J IRAN CHEM SOC
Fig. 2 TGA of HAP–Cu2O
Fig. 3 XRD of HAP–Cu2O
be inferred from the TEM micrographs that there is a pos-
sibility of molecular sieve formation in which the copper
oxide particles gets trapped (Fig. 6).
The characterization of silica-supported copper (I) oxide
has already been reported in the previous literature [14].
p-nitroaniline (1 mmol) for N-acetylation of amines and
p-nitrobenzylalcohol for O-acetylation of phenols/alcohols
and acetyl chloride (1 mmol) as acetylating agent were
selected as the test substrates to examine the catalytic effect
of supported copper (I) oxide.
The reaction using the test substrates and different sup-
ported copper (I) oxides (I–IV) in acetonitrile at 50 °C was
carried out to select the most suitable supported copper (I)
oxide and it was found that in the above-mentioned con-
ditions, HAP–Cu2O catalysed the acetylation reaction very
efficiently and furnished the products in excellent yields
Catalyst testing for N‑acetylation of amines
and O‑acetylation of phenols/alcohols
To optimize the reaction conditions for N-acetyla-
tion of amines and O-acetylation of phenols/alcohols,
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J IRAN CHEM SOC
Fig. 4 XPS of HAP–Cu2O
Fig. 5 SEM images of HAP–Cu2O
within 5 min (Table 1). Among the various acetylating
agents, acetyl chloride was found to be superior for N-acet-
ylation of amines and O-acetylation of phenols/alcohols.
Acetylation with acetic anhydride and acetic acid did not
give good results while the use of acetyl chloride as acet-
ylating agent proves to be very useful with our optimized
reaction conditions. While optimizing the reaction condi-
tions, 2.5 mol% of HAP–Cu2O was found to be sufficient
to carry out the reaction efficiently. Acetylation of amines,
phenols and alcohols was carried out at different tempera-
tures. At room temperature, reaction was quite slow but
a slight increase in reaction temperature, i.e. up to 50 °C
gave good-to-excellent results. When the reaction tempera-
ture was further raised to 80 °C, there is no enhancement
in the reaction rate and the yields are also same as obtained
when reaction was carried out at 50 °C.
amines were taken and the results are presented in Table 2.
It can be seen from the table that the yields of the acety-
lated product was excellent in each case which concludes
that the acetylation of amines shows functional group toler-
ance. The acetylation of phenols and alcohols was also car-
ried out and it can be seen that reaction with different ben-
zyl alcohols proceeds very efficiently in short span of time
while reaction with phenols takes much time for comple-
tion (Table 3). Reaction with aliphatic alcohols also gave
good results and furnished the products in good yields. In
general, acetylation of phenols and alcohols proceeds quite
slowly than amines.
To study the catalytic effect of hydroxyapatite–Cu2O,
the reaction was carried out with entry 7 Table 2, in the
absence of any catalyst. It is observed that the reaction
proceeds very slowly, i.e. 15 % in 2 h which clearly dem-
onstrates that hydroxyapatite–Cu2O catalyses the reaction
very efficiently and furnished the products in good-to-
excellent yields.
To study the applicability of developed protocol, various
anilines containing electron-releasing and electron-with-
drawing groups and aliphatic amine along with secondary
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J IRAN CHEM SOC
Fig. 6 TEM images of HAP–Cu2O
Catalyst testing for the synthesis of 2,4,5‑trisubstituted
imidazole
temperatures. Results are presented in Table 4. It can be
seen from the table that the reaction proceeded very effi-
ciently at 75–80 °C.
The reaction conditions for the synthesis of 2,4,5-trisub-
stituted imidazole were optimized by using benzil, benza-
ldehyde and ammonium acetate as the test substrates. To
establish the catalytic effect of supported copper (I) oxide,
the reaction was carried out with test substrates and differ-
ent supported copper (I) oxides (I–IV). It was observed that
the reaction proceeds with SiO2–Cu2O very efficiently and
produced good results. Different molar ratios of the selected
catalyst were used and it was seen that 5 mol% of the cata-
lyst is sufficient to carry out the synthesis of 2,4,5-trisub-
stituted imidazole. When the reaction between the test
substrates is performed in different solvents, ethanol was
found to be excellent solvent for this reaction. However, the
reaction was also carried out in solventless condition, but
the reaction is not clean and remained uncompleted with
our catalytic system. It is well known that reaction tem-
perature is also responsible for the desired rate of the reac-
tion. Therefore, synthesis of 2,4,5-trisubstituted imidazole
with the test substrates was also carried out with different
Various aldehydes with different electron-releasing and
electron-withdrawing groups were chosen and the reaction
was carried out benzil, aldehyde and ammonium acetate
in ethanol at 75–80 °C (Table 5). The reaction was carried
out using test substrates in ethanol at 75–80 °C without any
catalyst. It was observed that reaction did not give satisfac-
tory results in the absence of our catalytic system which
confirms the catalytic role of SiO2–Cu2O.
Recyclability of solid supported SiO2–Cu2O
For a catalyst to be heterogeneous, it must be recycla-
ble and reusable. To test the heterogeneity of the solid
supported SiO2–Cu2O, a series of six consecutive runs
has been carried out (Table 2, entry 7; Table 3, entry 11;
Table 5, entry 2). It has been observed that there is almost
no change in the activity of the catalyst up to sixth use. The
results are presented in the form of a graph (Fig. 7).
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J IRAN CHEM SOC
Table 2 HAP–Cu2O catalysed N-acetylation of amines in acetoni-
Table 3 HAP–Cu2O catalysed O-acetylation of phenols and alcohols
trile at 50°C
in acetonitrile at 50°C
S. no. Amine
Time (min) Yielda (%) M.pt./lit. M.pt.
S. no. Alcohols
Time (min) Yielda (%) M.pt./lit. M.pt.
1
2
Aniline
5
5
95
94
108–111/110–114
[57]
1
2
3
4
5
6
7
Phenol
30
60
180
180
30
8
90
85
92
87
80
89
93
Liq [64]
4-Nitrophenol
α-Naphthol
β-Naphthol
Resorcinol
Benzylalcohol
77–78/79–80 [50]
42–44/43–46 [57]
69–71/69–70 [57]
Liq [57]
4-Toluidine
152–154/152–153
[57]
3
4
3-Toluidine
2-Toluidine
7
4
92
92
64–66/65–66 [57]
108–110/109–111
[58]
Liq [50]
4-Chlorobenzy-
lalcohol
5
Liq [50]
5
4-Anisidine
8
94
127–128/129–130
[57]
8
4-Methoxyben-
zylalcohol
4
5
6
5
6
5
90
91
92
93
89
90
Liq [64]
6
7
2-Anisidine
5
8
91
94
88–89/87–88 [57]
4-Chloroaniline
176–177/178–180
[57]
9
4-Methylbenzy-
lalcohol
Liq [59]
8
3-Chloroaniline
2-Chloroaniline
7
5
90
92
94
78–79/79–81 [59]
86–88/87–88 [57]
10
11
12
13
4-Bromobenzy-
lalcohol
Liq [64]
9
10
4-Bromoaniline 10
165–166/166–167
[60]
4-Nitrobenzyla-
lcohol
77–79/76–78 [64]
53–55/54–55 [65]
38–40/39–40 [65]
11
12
13
4-Fluoroaniline
4-Nitroaniline
3-Nitroaniline
6
5
8
93
95
93
152–154/151–153
[61]
3-Nitrobenzyla-
lcohol
213–214/214–215
[57]
2-Nitrobenzyla-
lcohol
153–155/154–155
[57]
14
15
16
17
Isopropanol
Amyl alcohol
1-Butanol
15
12
18
10
88
85
86
90
Liq/liq [50]
Liq/liq [62]
Liq/liq [59]
Oil/oil [66]
14
15
16
17
18
19
2-Nitroaniline 12
90
94
93
90
92
89
91–93/92–94 [57]
Liq/liq [62]
Liq/liq [62]
Liq/liq [63]
Liq/liq [63]
Liq [50]
Morpholine
Piperidine
4
4
Benzyl thiol
Optimized reaction conditions: alcohol (1 mmol), acetyl chloride
(1 mmol), HAP–Cu2O (0.1 g), acetonitrile (5 mL) at 50 °C
Butylamine
Isopropylamine
Diethylamine
5
6
a
Yields refer to separation through column chromatography or
15
through crystallization
Optimized reaction conditions: amine (1 mmol), acetyl chloride
(1 mmol), HAP–Cu2O (0.1 g), acetonitrile (5 mL) at 50 °C
Table 4 Effect of temperature on the SiO2–Cu2O catalysed synthesis
a
of 2,4,5-trisubstituted imidazolea
Yields refer to separation through column chromatography or
through crystallization
S. no.
Temperature (°C)
Time (min)
Yieldb (%)
1
2
3
4
30
50
60
80
15
15
15
15
10
40
75
90
Proposed mechanism
Mechanism for acetylation of amines and alcohols
catalysed by HAP–Cu2O
a
Optimized reaction conditions: benzil (1 mmol), benzaldehyde
(1 mmol), ammonium acetate (4 mmol), SiO2–Cu2O (0.2 g) in etha-
nol (5 mL)
A plausible mechanism via metallacycle for the acetyla-
tion of amines and alcohols has been proposed. The first
step involves the activation of acyl halide ‘A’ by HAP–
Cu(I) to form transition state ‘B’. Due to this, the bond
between carbonylic carbon and oxygen gets weakened
which further assists the attack of nucleophilic atom (i.e.
N or O) on the carbonyl carbon (nucleophilic centre)
which leads to other transition state ‘C’. Finally, product
‘D’ was obtained with the regeneration of metal catalyst
(Fig. 8).
b
Yields refer to separation through column chromatography or
through crystallization
Mechanism for the synthesis of 2,4,5‑trisubstituted
imidazoles catalysed by SiO2–Cu2O
A cyclic mechanism for the synthesis of 2,4,5-trisubsti-
tuted imidazoles has been proposed. It involves metacycles
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J IRAN CHEM SOC
Table 5 SiO2–Cu2O catalysed
synthesis of 2,4,5-trisubstituted
imidazole in ethanol at 80°C
S. no.
Aldehyde
Time (min)
Yielda (%)
M.pt./lit. M.pt.
1
Benzaldehyde
15
45
90
88
87
88
80
85
84
75
82
85
92
90
92
272–273/274 [52]
2
4-Chlorobenzaldehyde
2-Chlorobenzaldehyde
4-Bromobenzaldehyde
4-Hydroxybenzaldehye
4-Nitrobenzaldehyde
3-Nitrobenzaldehyde
2-Nitrobenzaldehyde
Tolualdehyde
259–260/260–261 [67]
188–189/188 [52]
3
50
4
75
262–264/263–265 [67]
268–269/267–269 [51]
239–241/241–242 [51]
314–316/>300 [52]
232–233/230–231 [51]
229–231/230–233 [67]
228–229/230 [52]
5
90
6
70
7
50
8
120
60
9
10
11
12
13
Anisaldehyde
60
Salicyldehyde
60
204–206/204–205 [51]
188–189/189–191 [68]
256–258/257 [52]
Furfural
90
4-(Dimethylamino)benzaldehyde
100
Optimized reaction conditions: benzil (1 mmol), aldehyde (1 mmol), ammonium acetate (4 mmol), SiO2–
Cu2O (0.2 g), ethanol (5 mL) at 80 °C
a
Yields refer to separation through column chromatography or through crystallization
O
N-Acetylation of amines
O-Acetylation of alcohols
Synthesis of 2,4,5-trisubstituted imidazole
HCl
R1
Cl
'A'
HAP-Cu(I)
95
94
93
92
91
90
89
88
87
86
85
84
HAP
Cu(I)
O
.
HCl
HAP-Cu(I)
R1 Cl
Transition state
'B'
O
C
R2
X
R1
HAP
Cu(I)
'D'
O
R1 Cl
Transition state
'C'
R2 XH
NH, O
1
2
3
4
5
6
X
Number of runs
Fig. 8 Proposed mechanism for acetylation of amines/alcohols/phe-
nols
Fig. 7 Recyclability of solid supported SiO2–Cu2O
(I–III) which show the role of SiO2–Cu(I) for the activa-
tion of carbonyl carbon towards nucleophilic attack at dif-
ferent stages of the mechanism. It decreases the energy of
transition states and thus facilitates the reaction. Firstly,
attack by nitrogen obtained from ammonium acetate and
in situ generated imine towards carbonyl carbon resulted
in the formation of α-imino ketone and aryl aldimine leads
to the formation of the intermediate (A). Finally, intramo-
lecular cyclization of the intermediate followed by dehy-
dration leads to the formation of trisubstituted imidazoles
(Fig. 9).
Conclusions
In conclusion, we have synthesized different recyclable
solid supported copper (I) oxides and compared their activ-
ity for different organic transformations. We have explored
its applications for N-benzylation of primary amines [14],
N-benzylation of secondary amines [14], triazole synthe-
sis via click chemistry [53]. Keeping in view of the above
reported applications, we tried to explore more applications
of the solid supported copper (I) oxide catalysts in this
paper such as N-acetylation of amines, O-acetylation of
1 3

J IRAN CHEM SOC
NH4OAc
NH3
Fig. 9 Proposed mechanism for
the synthesis of trisubstituted
imidazoles
OH
Ph
Ph
NH
CH
O
SiO2-Cu(I)
R
Ph
Ph
O
O
OH
NH
Cu(I)
SiO2
OH
Ph
Ph
Ph
NH
CH
CH
Ph
O
Cu(I)
SiO2
O
III
II
R
R
NH3
Ph
Ph
O
O
Ph
Ph
O
O
SiO2-Cu(I)
Cu(I)-SiO2
NH
-H2O
Cu(I)-SiO2
H
R
OH
Ph
Ph
NH
SiO2-Cu(I)
R
CH
NH
NH4OAc
NH3
R
O
I
A
H
R
O
Cu(I)-SiO2
H
OH
Ph
Ph
NH
CH
Ph
Ph
N
-H2O
R
N
H
R
Ph
Ph
N
H
N
H
N
H
R
11. Y.R. de Miguel, E. Brule, R.G. Margue, J. Chem. Soc. Perkin
Trans. 1, 3085 (2001)
phenols and alcohols and synthesis of 2,4,5-trisubstituted
imidazole. It has been observed that different solid sup-
ported copper (I) oxide catalysts work very efficiently for
different organic reactions using simple and clean proce-
dures. The catalysts being selective, recyclable and hetero-
geneous make the methodologies more advantageous that
fall in the domain of Green Chemistry.
12. B.A. Lorsbach, M.J. Kurth, Chem. Rev. 99, 1549 (1999)
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1638 (2011)
Acknowledgments We are grateful to Director, SAIF, Punjab Uni-
versity, Chandigarh, for TEM and XRD and also to Head, SAIF, IIT
Bombay, for recording SEM images. We extend our sincere thanks to
UGC, New Delhi, for financial support to purchase FTIR; awarding
Major Research Project F 41‐281/2012 (SR), and Prof. R.K. Bamezai,
Department of Chemistry, University of Jammu, for recording TGA.
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