Acetylation of alcohols and phenols under solvent-free conditions using copper zirconium phosphate

Article abstract of DOI:10.1016/S1872-2067(14)60185-6

Copper zirconium phosphate nanoparticles have been used as an efficient catalyst for the acetylation of a wide range of alcohols and phenols with acetic anhydride in good to excellent yields under solvent-free conditions. The steric and electronic properties of the different substrates had a significant influence on the reaction conditions required to achieve the acetylation. The catalyst used in the current study was characterized by inductively-coupled plasma optical emission spectroscopy, energy dispersive spectroscopy, X-ray diffraction, N₂ adsorption-desorption, scanning electron microscopy, and transmission electron microscopy. These analyses revealed that the interlayer distance in the catalyst increased from 7.5 to 8.0 ? when Cu²⁺ was intercalated between the layers, whereas the crystallinity of the material was reduced. This nanocatalyst could also be recovered and reused at least six times without any discernible decrease in its catalytic activity. This new method for the acetylation of alcohols and phenols has several key advantages, including mild and environmentally friendly reaction conditions, as well as good to excellent yields and a facile work-up.

Full text of DOI:10.1016/S1872-2067(14)60185-6

Chinese Journal of Catalysis 35 (2014) 1982–1989
a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c h n j c
Article
Acetylation of alcohols and phenols under solvent‐free conditions
using copper zirconium phosphate
Abdol R. Hajipoura,b,*, Hirbod Karimia,c
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan University of Technology, Isfahan 84156, Iran
b Department of Neuroscience, University of Wisconsin, Medical School, Madison, WI 53706‐1532, USA
c Young Researchers and Elite Club, Shahreza Branch, Islamic Azad University, Isfahan, Iran
A R T I C L E I N F O
A B S T R A C T
Article history:
Copper zirconium phosphate nanoparticles have been used as an efficient catalyst for the acetyla‐
tion of a wide range of alcohols and phenols with acetic anhydride in good to excellent yields under
solvent‐free conditions. The steric and electronic properties of the different substrates had a signif‐
icant influence on the reaction conditions required to achieve the acetylation. The catalyst used in
the current study was characterized by inductively‐coupled plasma optical emission spectroscopy,
energy dispersive spectroscopy, X‐ray diffraction, N2 adsorption‐desorption, scanning electron
microscopy, and transmission electron microscopy. These analyses revealed that the interlayer
distance in the catalyst increased from 7.5 to 8.0 Å when Cu2+ was intercalated between the layers,
whereas the crystallinity of the material was reduced. This nanocatalyst could also be recovered
and reused at least six times without any discernible decrease in its catalytic activity. This new
method for the acetylation of alcohols and phenols has several key advantages, including mild and
environmentally friendly reaction conditions, as well as good to excellent yields and a facile
work‐up.
Received 18 May 2014
Accepted 1 July 2014
Published 20 December 2014
Keywords:
Copper zirconium phosphate
Nanoparticles
Acylation
Heterogeneous catalysis
Solvent‐free
© 2014, Dalian Institute of Chemical Physics, Chinese Academy of Sciences.
Published by Elsevier B.V. All rights reserved.
1. Introduction
also been reported that ZP possesses excellent selectivity to‐
wards Pb2+, Zn2+, and Fe3+ as an ion exchanger [15–17]. Fur‐
α‐Zirconium phosphate (ZP) is one of the most important
compounds in inorganic chemistry, and the layered structure
of this material has been used in a variety of different fields
[1–3]. ZP behaves as a unique ion exchanger because of its ex‐
ceptionally poor aqueous solubility, high thermal stability, re‐
sistance to radiation and abrasive properties [4,5]. The H+ of
the P–OH moiety in ZP can be exchanged for various other ions,
which results in the enlargement of the interlayer distance
[6–9]. Several studies pertaining to the successful exchange of
the H+ of the P–OH group in ZP with various divalent and triva‐
lent cations have been reported in the literature [10–14]. It has
thermore, ZP has been reported to exhibit antibacterial activity
when it was loaded with Cu2+, Zn2+, or Ce3+ [5,6,13,14]. Several
reports have also appeared in the literature concerning the
catalytic activities of ion exchanged materials of this type, in‐
cluding the use of zinc zirconium phosphate as a catalyst in the
Prins Condensation and the use of a zirconium phos‐
phate‐ferric chloride complex and potassium iron zirconium
phosphate as catalysts in Friedel‐Crafts acylation reactions
[18–24].
The acetylation of alcohols, phenols, thiols, and amines is
one of the most important and frequently used transformations
* Corresponding author. Tel: +98‐311‐3913262; Fax: +98‐311‐3913252; E‐mail: haji@cc.iut.ac.ir
This work was supported by the Isfahan University of Technology(IUT), Iran.
DOI: 10.1016/S1872‐2067(14)60185‐6 | http://www.sciencedirect.com/science/journal/18722067 | Chin. J. Catal., Vol. 35, No. 12, December 2014

Abdol R. Hajipour et al. / Chinese Journal of Catalysis 35 (2014) 1982–1989
1983
in organic synthesis, and the resulting acetylated species can be
used in a variety of different ways, including their application
as protecting groups in multistep synthetic processes. Acety‐
lated groups are also commonly found in cosmetics and food‐
stuffs, as well as fragrances, solvents, plasticizers, and pharma‐
ceuticals [25–27]. One of the most common examples of a
compound containing an acetylated group is aspirin, which is
produced by the acetylation of salicylic acid with acetic anhy‐
dride (AA) in the presence of an acid catalyst [28]. The acetyl
group is one of the most inexpensive and commonly used pro‐
tecting groups in organic chemistry for the protection of –OH,
–SH, and –NH2 functional groups because the resulting acety‐
lated compounds are stable to various reaction conditions and
reagents. Furthermore, the acetyl group can be readily intro‐
duced using inexpensive reagents and easily removed using
mild alkaline hydrolysis [29–31]. A variety of different proce‐
dures have been developed for the acetylation of alcohols,
phenols, amines, and thiols using both homogeneous and het‐
erogeneous catalysts such as VIV(TPP)(OTf)2 [27], La(NO3)3·
6H2O [29], B(C6F5)3 [30], CuSO4·5H2O [31], ZnCl2 [32], borated
zirconia [33], ZnO2 [34], Ce(OTf)3 [35], Si‐ZnCl2 [36],
H3PW12O40 [37], DMAP·HCl [38], Cu(BF4)2·xH2O [39], sili‐
ca‐bonded sulfamic acid [40], Cp2ZrCl2 [41], [TMBSA][HSO4]
[42], [bmim][OTs] [43], [MMPPA][HSO4] [44], SaSA [45],
SBNPSA [46], SuSA [47], P(4‐VPT) [48], acylimidazolium ace‐
tate [49], polyvinylpolypyrrolidoniume tribromide [50],
ZnAl2O4@SiO2 [51], P2O5/Al2O3 [52], [Hmim]HSO4 [53], Yt‐
tria‐zirconia [54], and CoCl2 [55]. Despite extensive interest in
development of new methods of acetylation, there is still scope
for the development of simple, efficient, inexpensive, widely
applicable, reusable and environmentally benign catalysts and
procedures capable of promoting the acetylation process.
With this in mind, and as part of ongoing work towards the
development of efficient green catalysts for organic transfor‐
mations [56,57], with particular emphasis on the acetylation
and acylation of aromatic compounds [52,53], we report herein
the use of copper zirconium phosphate (ZPCu) as an efficient
catalyst for the mild and convenient acetylation of alcohols and
phenols under solvent‐free conditions. This new ZPCu catalyst
was characterized by inductively‐coupled plasma optical emis‐
sion spectroscopy (ICP‐OES), energy dispersive X‐ray (EDX),
X‐ray diffraction (XRD), N2 adsorption‐desorption, scanning
electron microscopy (SEM), and transmission electron micros‐
copy (TEM).
filtered, and the filter cake was then washed with a solution of
H3PO4 (0.1 mol/L) until the filtrate was free of chloride ions.
The filter cake was then washed several times with distilled
water until the pH of the filtrate was neutral. The solid was
then collected and dried in an oven at 110 °C for 24 h [2]. ZPCu
was prepared through an ion‐exchange reaction [8–10]. Briefly,
ZP (3 g) was dispersed in deionized water (50 ml) at 50 °C, and
the resulting suspension was treated with a solution of
Cu(OAc)2 (100 ml, 0.1 mol/L) in water (excess amount of Cu2+).
This mixture was then heated at reflux for 4 d. It is noteworthy
that the acetate ion performed effectively as a base to keep the
hydrogen ion concentration in solution sufficiently low to
achieve high loadings of the catalyst [7]. A complete exchange
between the cations and the hydrogen ions of the P–OH groups
could not be achieved in less than 3 d or at temperatures below
80 °C [13]. The resulting slurry was filtered hot (~X °C) to give
a light blue solid, which was washed with distilled water until
no Cu2+ ions could be detected in the filtrate (i.e., until the fil‐
trate was colorless). The solid product was then dried at 100 °C
for 24 h before being calcined at 600 °C for 5 h to give the final
product, ZPCu, as a pale blue solid (Scheme 1).
2.2. Catalyst characterization
The chemical composition of the ZPCu catalyst was evalu‐
ated at different stages of the reaction (i.e., before and after the
catalytic reaction) by ICP‐OES using an Optima 7300 V ICP‐OES
spectrometer (PerkinElmer). The chemical composition of the
ZPCu catalyst was measured by energy dispersive X‐ray spec‐
troscopy (EDS) using a Zeiss EVO scanning electron microscope
operating at 20 kV. The samples were ground into a fine pow‐
der and analyzed by XRD on a Philips X’pert X‐ray diffractome‐
ter.
The specific surface areas of the samples were determined
from their N2 adsorption‐desorption isotherms using the
Brunauer‐Emmett‐Teller (BET) method on a Quantachrome
ChemBET 3000 instrument (Supplier, City, Country). Each
sample was degassed at 400 °C for 2 h before being analyzed to
remove any adsorbed species from their surfaces. The BET
surface areas of the materials were estimated from their N2
adsorption‐desorption isotherms.
The surface morphologies of the ZP and ZPCu materials
were studied by SEM on a Philips XL scabbing electron micro‐
scope (Philips). TEM images of ZPCu were obtained on a
CENTRA 100 TEM system (Zeiss).
2. Experimental
2.3. General experimental procedure for the acetylation of
2.1. Catalyst synthesis
substrates under solvent‐free conditions
OH
P
OH
P
All of the reagents and solvents used in the current study
were purchased from Merck Chemical Company and used
without further purification. The catalyst was prepared ac‐
cording to previously published procedures, with minor modi‐
fications [2,8–10]. ZP was prepared according to the following
procedure. ZrOCl2·8H2O (5 g) was heated at reflux in a solution
of H3PO4 (50 ml, 12 mol/L) for 24 h. The resulting mixture was
cooled to ambient temperature to give a suspension, which was
H3PO4
110 o
C
Zr 4+ solution
White precipitate of
zirconium phosphate
100 oC, 24 h
Zr
Zr
24 h
Cu2+
O
P
O
P
600 oC
5 h
Drying at o
24 h
C
Cu(AcO)2
Reflux, 4 d
Zr
Zr
CuZr(PO4)2
Scheme 1. Procedure for the preparation of ZPCu.

1984
Abdol R. Hajipour et al. / Chinese Journal of Catalysis 35 (2014) 1982–1989
ZPCu (2 mol%)
60-80 oC, 20-90 min
Table 1
R-OH
+ Ac2O
R-OAc + CH3CO2H
Elemental compositions of several different copper zirconium phos‐
phates (atm%).
R = aryl, alkyl, benzyl
Scheme 2. Procedure for the acetylation of phenols.
Entry
1
2
3 a
4 b
5 c
Sample
ZP
ZPCu
ZPCu
ZPCu
ZPCu
Cu
—
11.7
11.2
11.6
5.9
O
Zr
P
63.1
58.7
57.5
59.3
62.5
13.6
10.9
11.5
10.4
12.2
23.3
18.8
19.8
18.7
19.4
ZPCu (2 mol%)was added to a mixture of phenol (1 mmol)
and AA (2 mmol), and the resulting mixture was stirred at 60 °C
for the specified time (Scheme 2). Upon completion of the reac‐
tion (as determined by GC), the catalyst was separated from the
reaction mixture by centrifuge, then the supernatant was col‐
lected and diluted with 10% NaHCO3 solution (10 ml) before
being extracted with Et2O (2 × 10 ml). The combined organic
extracts were washed and then dried over anhydrous CaCl2
before being evaporated to dryness under vacuum to give the
desired product. In some cases, it was necessary for the prod‐
uct to be purified by column chromatography over silica gel
eluting with a mixture of cyclohexane and ethyl acetate.
a From EDS analysis. b After run 1. c After run 7.
ported for ZP and its derivatives with a hexagonal crystal sys‐
tem [2]. It shows that the d‐spacing of the (002) plane of ZPCu
had increased, which indicated that the Cu2+ ions had interca‐
lated into the interlayer of ZP and increased the d002 basal in‐
terlamellar spacing of ZP from 7.5 to 8.0 Å. It is well known that
the ion radii of Cu2+ (0.72 Å) [58,59] and hydrated Cu2+ (4.19 Å)
[60] are smaller than the basal spacing of ZP (7.5 Å). These
results therefore indicated that Cu2+ ions had inserted into the
interlayer of ZP and increased the basal spacing of the modified
ZP after the exchange [8–10]. Taken together, these data indi‐
cated that ZPCu had been formed successfully. The XRD pattern
of the ZPCu catalyst after the 7th run showed that the basal
spacing of ZP was about 8.5 Å, which was only a little larger
than that of the fresh ZPCu catalyst. This increase may have
occurred because of the presence of less Cu2+ on the surface of
ZP, and an increase in the number of water molecules between
the layers following the seventh run (i.e., Cu2+ ions may have
been washed off during the regeneration of the catalyst, section
2.3 and Table 1).
2.4. Recyclability studies of catalyst
To examine the recyclability of the catalyst, the used ZPCu
was recovered from the reaction media and re‐used. For recy‐
cling, after the first use, the catalyst was separated from the
reaction mixture by centrifugation and washed with sequen‐
tially with ethanol and water before being dried at 110 °C for 2
h.
3. Results and discussion
Figure 3 shows the N2 adsorption‐desorption isotherm of
ZPCu, as a representative example, in the relative pressure
range (p/p0) of 0.1–1.0. The surface area of ZPCu was deter‐
mined to be 93.1 m2/g.
The isotherm for ZPCu shows three adsorption stages. The
first of these stages was observed at p/p0 < 0.47, whereas the
second stage was observed in the range of 0.47 < p/p0 < 0.93,
and the third stage was observed at higher relative pressures
(p/p0 > 0.93). The N2 adsorption‐desorption isotherm of ZPCu
exhibited a typical “type IV” isotherm shape with a distinct
hysteresis loop, which is characteristic of a mesoporous mate‐
3.1. Catalyst characterization results
The EDS and ICP‐OES analyses of ZPCu are shown in Fig. 1
and Table 1 (entry 3), respectively. The results obtained in the
current study for ZPCu were compared with those reported
previously in the literature [5,9,10]. Our results reveled that
there was a negligible leach of copper ions into the reaction
media after the reaction (i.e., following the first use of the cata‐
lyst).
Figure 2 shows the powder XRD patterns of the ZP and ZPCu
materials. The results show some characteristic reflections in
the 2θ range of 5°–40°. The diffraction peak in ZP at 2θ ~ 12°
was assigned to a d002 basal spacing of 7.5 Å between the
planes, which was consistent with the patterns previously re‐
15
Zr
P
ZPCu (7th run)
Zr
Cu
Cu
O
10
5
ZPCu (Fresh)
ZP
0
5
10
15
20 25
2/(o )
30
35
40
0
2
4
6
8
10
Energy (keV)
Fig. 2. XRD patterns of powdered ZP, fresh ZPCu, and ZPCu after the 7th
run.
Fig. 1. EDS spectrum of ZPCu.

Abdol R. Hajipour et al. / Chinese Journal of Catalysis 35 (2014) 1982–1989
1985
100
90
80
70
60
50
40
(a)
(b)
Adsorption
Desorption
100 nm
50 nm
(d)
(c)
0.0
0.2
0.4
0.6
0.8
1.0
p/p0
Fig. 3. N2 adsorption‐desorption isotherm of ZPCu.
100 nm
75 nm
rial [61]. The hysteresis loop (type H3) is associated with the
occurrence of capillary condensation in the mesopores, which
indicates the presence of a mesoporous structure in the ZPCu
catalyst. The observed increase in adsorption at the higher p/p0
value indicated the presence of larger mesopores in the sample
[10]. The surface area of ZPCu after the 7th run was found to be
85.4 m2/g.
The SEM image of ZP (Fig. 4(a)) revealed the presence of
hexagonal plates with well‐defined shapes and very smooth
surfaces. Figure 4(b) and (c) show the SEM images of ZPCu.
These images revealed that the structure of ZPCu was much
less ordered than that of ZP, and that the ZPCu particles had
aggregated to form both sheets and spheres of different shapes
and sizes.
Fig. 5. TEM images showing the regular morphology of freshly pre‐
pared ZPCu (a–c) and the same material after its 7th run (d).
3.2. Catalytic activity of ZPCu towards the acetylation of
phenols and its expected mechanism
The conversion of phenol (1 mmol) to phenyl acetate was
selected as a model reaction to optimize the conditions, and the
reaction was conducted in the presence of ZPCu (2 mol %) and
AA (2 mmol) in various solvents, as well as being investigated
under solvent‐free conditions. As shown in Table 2, the use of
ZPCu as a catalyst under solvent‐free conditions provided
higher yields and shorter reaction times than those achieved
under conventional conditions.
Figure 5 shows the TEM images of ZPCu. It shows that ZPCu
catalyst retained the original morphology of ZP (layered struc‐
ture) and that the particles were approximately 200 nm in size.
These images also showed nanoparticles of different sizes on
the smooth surface of the ZP. The presence of metallic crystal
nanoparticles on the surface of ZP indicated that the copper
deposited on the surface of the ZP had agglomerated. Similar
observations have also been reported for zinc and cerium with
ZP [6,14]. Figures 4(d) and 5(d) show the SEM and TEM images
of the catalyst following its 7th run, respectively. Both of these
images showed that the sheets and particles had conglomerat‐
ed to a much greater extent following the 7th run because of
the process used to regenerate the catalyst.
With the optimized conditions in hand, we proceeded to
evaluate the scope and generality of the method using various
alcohols and phenols (Table 3). Pleasingly, the hydroxyl groups
of the all of different alcohol and phenols tested were convert‐
ed to the corresponding acetates in good yields and short reac‐
tion times using 3 or 4 equivalents of AA (Table 3, entries 8–10,
20). Furthermore, the products were readily isolated from the
reaction mixtures by a simple filtration followed by a standard
work‐up procedure. Phenols reacted smoothly under the opti‐
mized conditions (Table 3, entries 1–15), with the correspond‐
ing acetates being formed in yields of 80%–95%. Furthermore,
no by‐products (such as those resulting from a Fries rear‐
rangement) were observed with the substituted phenols. The
presence of electron‐donating substituents (i.e., –CH3, –OCH3,
–OH) on the phenol ring led to a significant increases in the rate
of the acetylation reaction (Table 3, entries 2–10), with shorter
reaction times being observed in these cases. On contrast, the
(a)
(b)
Table 2
Conversion of phenol to phenylacetate in different solvents and under
solvent‐free conditions in the presence of ZPCu (2 mol%).
(c)
(d)
Entry
Solventa
Dichloromethane
Diethylether
Acetonitrile
Cyclohexane
Solvent‐free
Yield b (%)
Trace
Trace
Trace
51
Time (min)
120
1
2
3
4
120
120
90
30
5
a
91
The reaction was carried out in 5 ml of solvent under reflux condi‐
tions.
Fig. 4. SEM images showing the regular morphology of ZP (a), fresh
b The yields refer to isolated pure product.
ZPCu (b, c), and ZPCu after the 7th run (d).

1986
Abdol R. Hajipour et al. / Chinese Journal of Catalysis 35 (2014) 1982–1989
Table 3
Acetylation of phenols with AA under solvent‐free conditions in the presence of ZPCu.
Entry
1
2
3
4
5
6
7
8
Substrate
C6H5OH
Product a
C6H5OAc
Time (min)
T (°C)
60
60
60
60
60
60
60
60
60
60
80
80
80
80
Substrate/AA molar ratio
Isolated yield (%)
30
30
20
45
20
20
20
30
30
45
90
90
90
75
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:3
1:3
1:4
1:3
1:3
1:3
1:3
90
92
95
87
95
94
95
91
90
90
83
85
80
90
2‐Me‐C6H4OH
4‐Me‐C6H4OH
2,6‐(Me)2‐C6H3OH
2,4‐(Me)2‐C6H3OH
4‐(CH3)3C‐C6H4OH
4‐MeO‐C6H4OH
4‐OH‐C6H4OH
3‐OH‐C6H4OH
2,3‐di‐OH‐C6H3OH
4‐Cl‐C6H4OH
2‐Me‐C6H4OAc
4‐Me‐C6H4OAc
2,6‐(Me)2‐C6H3OAc
2,4‐(Me)2‐C6H3OAc
4‐(CH3)3C‐C6H4OAc
4‐MeO‐C6H4OAc
4‐AcO‐C6H4OAc
3‐AcO‐C6H4OAc
2,3‐di‐AcO‐C6H3OAc
4‐Cl‐C6H4OAc
9
10
11
12
13
14
4‐Br‐C6H4OH
4‐NO2‐C6H4OH
2‐OH‐C6H4CO2H
4‐Br‐C6H4OAc
4‐NO2‐C6H4OAc
2‐AcO‐C6H4CO2H
15
16
17
18
19
20
21
22
23
24
25
26
4‐OH‐C6H4CO2H
2‐Naphthol
4‐AcO‐C6H4CO2H
2‐Naphthyl acetate
C6H5CH2OAc
80
60
60
60
60
60
60
60
60
60
60
60
60
30
30
30
20
20
30
30
20
20
20
45
1:3
1:2
1:2
1:2
1:2
1:3
1:2
1:2
1:2
1:2
1:2
1:2
92
91
91
93
95
90
86
84
94
93
95
89
C6H5CH2OH
2‐MeO‐C6H4CH2OH
4‐MeO‐C6H4CH2OH
4‐OH‐C6H4CH2OH
4‐Cl‐C6H4CH2OH
4‐NO2‐C6H4CH2OH
1‐Hexanol
2‐MeO‐C6H4CH2OAc
4‐MeO‐C6H4CH2OAc
4‐AcO‐C6H4CH2OAc
4‐Cl‐C6H4CH2OAc
4‐NO2‐C6H4CH2OAc
1‐Hexyl acetate
Cyclohexanol
Cyclohexyl acetate
3‐Methylbutyl acetate
(CH3)3C‐OAc
3‐Methyl‐1‐butanol
(CH3)3C‐OH
a All of the products were characterized by GC‐MS, IR, and 1H NMR analysis and a comparison of their data with those of the authentic samples or data
reported in the literature.
presence of electron withdrawing groups (i.e., carboxyl, nitro,
and halo groups) on the phenol ring led to a decrease in the
rate of the acetylation reaction (Table 3, entries 11–15), with
longer reaction times being observed. The optimized reaction
conditions were also successfully applied to the acetylation of
benzylic alcohols bearing an electron‐withdrawing or elec‐
tron‐donating group without the formation of any by‐products
resulting from oxidation reactions (Table 3, entries 17–22). For
deactivated aromatic rings (Table 3, entries 21 and 22), the
acetylated products were obtained in much lower yields and
required longer reaction times than the corresponding acti‐
vated aromatic systems (Table 3, entries 18–20).
ZPCu‐mediated acetylation process is shown in Scheme 3. To
develop a deeper understanding of the role of the ZPCu catalyst
in the acetylation reaction, we investigated the acetylation of
phenol, 4‐hydroxyphenol, and benzyl alcohol in the absence of
the catalyst. As expected, no products were formed in any of
these reactions, which demonstrated the importance of the
catalyst to the acetylation process. All of the acetylated prod‐
ucts formed in the current study were characterized by GC‐MS,
FT‐IR (JASCO FT‐IR 680 plus spectrophotometer; JASCO) and
1H NMR (Bruker‐Avance AQS 400 MHz spectrometer) analyses
and a comparison of these data with those of standard samples
or data from the literature [28,44,45,47–53].
The reaction times required for the acetylation of the phe‐
nols were longer than those required for the benzylic alcohols.
This difference in the reaction times was attributed to the low
nucleophilicity of phenols compared to benzylic alcohols be‐
cause of the delocalization of the lone pairs of electrons on the
phenolic oxygen throughout the benzene ring [43,49,51]. To
further extend the scope of the ZPCu catalyst, we also investi‐
gated the acetylation of several aliphatic alcohols, including
1‐hexanol, cyclohexanol, 3‐methyl‐1‐butanol, and tert‐butanol,
under the optimized conditions (Table 3, entries 23–26). The
acetylation reactions of 1‐hexanol cylohexanol, 3‐methyl‐1‐
butanol proceeded much more rapidly than the acetylation of
tert‐butanol, most likely because of the steric hindrance pro‐
vided by the tert‐butyl group. A schematic representation of the
O
O
O
O
+ O
Cu2+
O
O
Cu2+
O
O
O
P
Zr
P
Zr
P
Zr
P
Zr
O
O
+
R
O
CH3
OH
ROH
R = aryl, alkyl, benzyl
R = aryl, alkyl, benzyl
Scheme 3. Schematic representation of the current ZPCu‐mediated
acetylation process.

Abdol R. Hajipour et al. / Chinese Journal of Catalysis 35 (2014) 1982–1989
1987
The reusability of the ZPCu catalyst was investigated under
Table 4
the optimum reaction conditions for the acetylation of phenol,
and the results are shown in Table 4. The elemental composi‐
tion of the catalyst remained largely unchanged following its
7th run, although the amount of copper in the catalyst was re‐
duced by almost 50% compared with the first run (Table 1).
The recycled ZPCu catalyst gave a similar product yield to the
freshly prepared catalyst up until the sixth cycle.
The catalytic efficiency of ZPCu was compared with several
previously reported catalysts and protocols, and the results are
shown in Table 5. Phenol was converted to acetylphenol in
90% yield following a reaction time of less than 30 min at 60 °C
using the current protocol (Table 5, entry 16). Although some
of the other catalysts performed well for the same reaction
(Table 5, entries 2, 6, 10), they invariably required longer reac‐
tion times to reach completion (Table 5, entries 3, 6, 7, 9, 11, 13,
14) or required the use of a solvent (Table 5, entries 4, 6, 7, 9,
12). It is noteworthy that the more reactive acetyl chloride was
required in one case, where it was used at room temperature
(Table 5, entry 5). Furthermore, this reaction required a longer
Reusability of the ZPCu catalyst under the optimum reaction conditions
for the acetylation of phenol.
Run
Phenol conversion (%)
Fresh
90
90
88
87
87
85
81
72
1
2
3
4
5
6
7
Reaction conditions: phenol 1 mmol, Ac2O 2 mmol, catalyst 2 mol%, 60
°C.
reaction time to reach afford a similar yield of the acetylated
product to the current protocol. Some of the previously re‐
ported protocols used acetic acid as the acetylating agent, rep‐
resenting a much greener choice than acetyl chloride (Table 5,
entries 4, 8, 15), although these reaction required long reaction
times (3–15 h), high temperatures (70–110 °C) and a large
excess of acid acetic in almost all cases. The acetylation of phe‐
Table 5
Comparison of different protocols for the acylation of phenol and benzyl alcohol.
OAc
OH
CH2OH
CH2OAc
Ac2O , cat
Ac2O, cat
-
-
For entries 1 19
T (°C)
60
RT
RT
110
RT
RT
80
For entries 20 34
Ac2O (equiv.) Yield (%)
Entry
1
Catalyst
ZPZn
Time (min)
45
Solvent
—
Ref.
[22]
2
1.2
1
5 a
1.2 b
1.5
1.2
5 a
1.1
1
3 ml c
2
1.5
3 ml c
5 a
2
2
2
2
1.2
1
5 a
1.2
3 ml c
1
1.1
1.1
1.2
3 ml c
5 a
2
89
92
40
10
90
98
83
3
2
B(C6F5)3
15
—
[30]
3
ZnCl2
150
840
60
150
210
180
600
30
180
10
120
180
900
30
30
30
30
2
180
840
180
15
600
120
120
120
45
—
[32]
4
5
borate zirconia
ZnO
toluene
—
[33]
[34]
6
Ce(OTf)3
CH3CN
[35]
7
8
9
SiO2‐ZnCl2
H3PW12O40
DMAP·HCl
Cu(BF4)2
silica sulfamic acid
[bmim][OTs]
[MMPPA][HSO4]
SBNPSA
yttria‐zirconia
ZPCu
ZrOCl2·8H2O
ZP
CH3CN
—
toluene
—
[36]
[37]
[38]
[39]
[40]
[43]
[44]
[46]
70
RT
RT
RT
50
RT
RT
110
60
99
97
—
97
99
—
77
90
95
70
91
98
63
25
90
93
93
99
99
85
91
94
98
91
97
75
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
—
[bmim][BF4]
—
—
—
—
—
—
—
—
—
toluene
CH3CN
—
—
—
—
CH2Cl2
—
—
—
[54]
this work
this work
this work
[22]
[30]
[33]
[34]
[36]
[40]
[41]
[42]
[44]
[45]
[46]
[54]
[55]
this work
this work
this work
60
60
60
ZPZn
B(C6F5)3
ZnCl2
RT
RT
110
80
RT
RT
RT
RT
Reflux
R T
110
RT
60
borated zirconia
SiO2‐ZnCl2
silica sulfamic acid
Cp2ZrCl2
[TMBSA][HSO4]
[MMPPA][HSO4]
SaSA
SBNPSA
yttria‐zirconia
CoCl2
240
240
30
30
30
ZPCu
ZrOCl2·8H2O
ZP
2
2
2
—
—
—
60
60
a Acetic acid as the acetylating agent. b Acetyl chloride as the acetylating agent. c Ethyl formate as the acetylating agent. RT: room temperature.

1988
Abdol R. Hajipour et al. / Chinese Journal of Catalysis 35 (2014) 1982–1989
nol was also investigated usingZrOCl2·8H2O and ZP under our
optimized reaction conditions (Table 5, entries 17 and 18).
ZrOCl2·8H2O gave an excellent yield of the desired product, but
was much more difficult to recover and reuse than the ZPCu
catalyst. ZP gave a lower yield (70%) than ZPCu. The use of
ZPZn as a catalyst, however, provided a similar result to that of
ZPCu (Table 5, entry 1), with a 20 mol% loading of ZPZn
providing the acetyl phenol product in 89% yield following a
reaction time of 45 min [22]. Based on this comparison process,
ZPCu was identified the best catalyst for this transformation in
terms of the reaction time and the loading of the catalyst.
Benzyl alcohol was also acetylated under the optimized
conditions to give the acetylated product in 91% yield follow‐
ing a reaction time of 30 min at 60 °C (Table 5, entry 32). This
protocol was also compared with a variety of different previ‐
ously reported procedures for the same transformation, and
the results are shown in Table 5. When the reaction was con‐
ducted at room temperature in the presence of a different cat‐
alyst, it generally required longer reaction times to reach com‐
pletion (Table 5 entries 21, 25–27, 31). The use of ZPZn,
ZrOCl2·8H2Oor ZPas a catalyst under the optimized conditions
provided the desired product in yields of 91%, 97%, and 75%,
respectively (Table 5, entries 19, 33, 34). However, large ex‐
cesses of the catalyst were required in all three of these cases,
and significant difficulties were encountered during the recov‐
ery of these catalysts. These reactions also resulted in lower
yields of the product. There were, however, some benefits to
using these catalysts, in that they used acid acetic as an acety‐
lating agent instead AA, but they all required longer reaction
times, higher temperatures and a large excess of acid acetic to
reach completion (Table 5, entries 22 and 30).
1613, 1518, 1460, 1363, 1243, 1176, 1120, 1031, 960, 823
cm–1.
3‐Methylbutyl acetate (Table 3, entry 23). 1H NMR (400
MHz, CDCl3): δ = 4.18 (t, J = 6.6 Hz, 2H), 2.1 (s, 3H), 1.58–1.67
(m, 1H), 1.43–1.5 (m, 2H), 0.96 (d, J = 3.4, 6H); IR (KBr): 2962,
2935, 1743, 1465, 1430, 1249, 1172, 1136, 1065, 962, 857
cm–1.
4. Conclusions
ZPCu is an inexpensive, noncorrosive, and environmentally
benign catalyst that can be readily prepared from simple start‐
ing materials. This catalyst was characterized using various
analytical methods and the results were in agreement with
those reported previously in the literature. In this study, we
have developed a simple and efficient procedure for the acety‐
lation of a variety of different alcohols in good yields over short
reaction times. There are several notable advantages to this
methodology, including a broad substrate scope, the use of AA
as an acetylating agent, excellent product yields and easy
work‐up procedure resulting from the heterogeneous condi‐
tions.
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Graphical Abstract
Chin. J. Catal., 2014, 35: 1982–1989 doi: 10.1016/S1872‐2067(14)60185‐6
Acetylation of alcohols and phenols under solvent‐free
conditions using copper zirconium phosphate
Abdol R. Hajipour*, Hirbod Karimi
Isfahan University of Technology, Iran;
University of Wisconsin, USA;
Young Researchers and Elite Club, Iran
Copper zirconium phosphate was prepared and used as an effi‐
cient and reusable nanocatalyst for the acetylation of alcohols
with fairyields. The method conforms to several of the guiding
principles of green chemistry.
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