Impregnated copper on Fe3O4: an efficient magnetically separable nanocatalyst for rapid and selective acylation of amines

Article abstract of DOI:10.1007/s13738-017-1181-2

The present paper describes the synthesis of N-arylacetamides through acetylation of arylamines with Ac₂O in the presence of magnetically recyclable Fe₃O₄/Cu NPs. All reactions were carried out efficiently in H₂O within 2–10?min to give the products in 89–95% yields. Selective acetylation of amines versus alcohols was carried out successfully with this acetylating system. In addition, acetylation of amines and phenols was taken place with the same reactivity. Reusability of the nanocatalyst was examined 5 times without significant loss of its catalytic activity.

Full text of DOI:10.1007/s13738-017-1181-2

J IRAN CHEM SOC
DOI 10.1007/s13738-017-1181-2
ORIGINAL PAPER
Impregnated copper on Fe3O4: an efcient magnetically separable
nanocatalyst for rapid and selective acylation of amines
Zahra Shokri1 · Behzad Zeynizadeh1
Received: 17 January 2017 / Accepted: 17 August 2017
© Iranian Chemical Society 2017
Abstract The present paper describes the synthesis of
N-arylacetamides through acetylation of arylamines with
Ac2O in the presence of magnetically recyclable Fe3O4/Cu
NPs. All reactions were carried out efciently in H2O within
2–10 min to give the products in 89–95% yields. Selective
acetylation of amines versus alcohols was carried out suc-
cessfully with this acetylating system. In addition, acetyla-
tion of amines and phenols was taken place with the same
reactivity. Reusability of the nanocatalyst was examined 5
times without signifcant loss of its catalytic activity.
reusability [18, 19]. In this context, more attention has been
paid to core–shell nanocomposite systems with the core of
magnetite (Fe3O4). They are simply prepared and because of
their good magnetic properties are easily removed from the
reactions. Functionalized magnetic nanoparticles (MNPs)
are robust, air-stable and frequently used for immobilization
of various heterogeneous [20–31] and homogenous [32–34]
catalysts. In addition, they are close in catalytic activity in
respect of the corresponding homogeneous catalysts.
Metal nanoparticles because of high catalytic activities
owing to their extremely small dimensions and large surface
areas have attracted a great deal of attentions. In spite of high
catalytic activity and selectivity which achieved with noble
metals, their high cost and difcult separation from the reac-
tion mixture are the major disadvantages. Therefore, replace-
ment of inexpensive non-noble metals catalysts with noble
metals is a requirement. Copper is a cheaper alternative in
respect of various noble metals [35, 36]. In addition, copper
NPs because of nanosize dimension and non-magnetic prop-
erty are not suitable for isolation from the reactions by con-
ventional techniques. These subjects prompted us to prepare
nano impregnated copper on magnetite with 22% Cu content
as an efcient and reusable nanocatalyst toward acetylation
of arylamines with Ac2O in H2O (Scheme 1).
Keywords Ac2O · Acetylation · Amines · Copper ·
Fe3O4/Cu · N-arylacetamides
Introduction
Selective protection of amines is one of the most important
methods for multistep synthesis of organic compounds [1,
2]. So, increasingly large numbers of documents have been
reported for this achievement [3–17]. Most of the reported
protocols sufer from disadvantages in term of using homo-
geneous and expensive catalysts, low yields, the use of
organic solvents, tedious and time-consuming workups.
These shortcomings were overcome by using heterogeneous
catalysts possessing high catalytic activity and the frequent
Results and discussion
Electronic supplementary material The online version of this
article (doi:10.1007/s13738-017-1181-2) contains supplementary
material, which is available to authorized users.
Synthesis and characterizations of Fe3O4/Cu MNPs
Synthesis of Fe3O4/Cu MNPs with 22% Cu content was car-
ried out in a two-step procedure: (1) preparation of nanopar-
ticles of Fe3O4 by a chemical co-precipitation of FeCl3·6H2O
and FeCl2·4H2O in aqueous ammonia (Scheme 2) and (2)
* Behzad Zeynizadeh
bzeynizadeh@gmail.com
1
Faculty of Chemistry, Urmia University, Urmia 5756151818,
Iran
Vol.:(0123456789)
1 3

J IRAN CHEM SOC
revealed that all characteristic peaks of a cubic spinel struc-
ture of pure Fe3O4 existed in the prepared sample (Fig. 2a).
The peaks at 30.2°, 35.5°, 43.3°, 53.7°, 57.2° and 62.9° are
attributed to 220, 311, 400, 422, 511 and 440 crystal planes
of pure Fe3O4.
Figure 2b shows X-ray difraction pattern of Fe3O4/Cu
MNPs. The pattern includes all characteristic peaks of Cu
and Fe3O4. The peaks at 2θ values of 43.5°, 50.8° and 74.6°
are attributed to 111, 200 and 220 crystal planes of cubic
structure of pure Cu (JCPDS 71-4610) [38]. The absence of
any further difraction peaks in XRD pattern of Fe3O4/Cu
represents high phase purity of the prepared nanoparticles.
Through the inductively coupled plasma-optical emission
spectrometry (ICP-OES), the amounts of Cu, Fe and O in
Fe3O4/Cu MNPs were determined 22.04, 56.41 and 21.55%,
respectively.
Scheme 1 Acetylation of amines with Ac2O in the presence of
Fe3O4/Cu MNPs
Scheme 2 Synthesis of Fe3O4 MNPs
Figure 3 shows the magnetic hysteresis loops of sam-
ples. It indicates that the products have super paramagnet-
ism characteristic. The decrease in saturation magnetization
(Ms) from 66.976 (Fe3O4) to 43.559 emu g−1 (Fe3O4/Cu)
is attributed to the presence of Cu shells around surface of
magnetite cores.
addition of Fe3O4 MNPs to aqueous solution of CuCl2·2H2O
followed by reduction with NaBH4 (Scheme 3).
After synthesis of Fe3O4/Cu MNPs, the size and morphol-
ogy of nanoparticles was studied using scanning electron
microscopy. The SEM image (Fig. 1) shows that the catalyst
was made from granular nanoparticles with size distribution
from 15 to 20 nm. The image also represents the particles
are agglomerated to some extent.
Acetylation of arylamines with Ac2O in the presence
of Fe3O4/Cu MNPs
A comparison between XRD pattern of the prepared
Fe3O4 with standard magnetite (JCPDS 65-3107) [37]
At the next, the catalytic activity of Fe3O4/Cu MNPs was
studied by acetylation of arylamines with Ac2O. In order to
Scheme 3 Fabrication of
Fe3O4/Cu MNPs
1 3

J IRAN CHEM SOC
was the requirement for complete conversion of aniline to
acetanilide within 3 min at 50 °C (Table 1, entry 8).
The scope and generality of this synthetic protocol was
then studied through acetylation of structurally diverse
aromatic amines at the optimized reaction conditions.
The summarized results in Table 2 show that acetylation
of arylamines possessing electron-releasing or withdraw-
ing groups was carried out successfully with 1 mmol of
Ac2O in the presence of 0.05–0.2 mmol of Fe3O4/Cu MNPs
within 2–10 min (50 °C). The product N-arylacetamides
were obtained in high to excellent yields. Molecules with
the functionality of hydroxyl alcohol and amine showed
an excellent selectivity for acetylation of amino group. All
attempts for acetylation of hydroxyl alcohol were unsuccess-
ful even under drastic reaction conditions (Table 2, entry
15). So, this is a valuable practically success in acetylation
of amines versus alcohols. In the case of molecules hav-
ing phenolic and amino groups, the present protocol did not
show any selectivity and both of functional groups were
acetylated with the same reactivity. This fact was shown with
acetylation of 3-aminophenol to 3-acetamidophenyl acetate
(Table 2, entry 16). It is notable that the complete acetyla-
tion of phenolic amines requires higher molar equivalents
of Ac2O and Fe3O4/Cu MNPs.
Fig. 1 SEM image of Fe3O4/Cu MNPs
The catalytic activity of Fe3O4/Cu MNPs for acetylation
of PhNH2 with Ac2O was highlighted by comparison of the
obtained results for current protocol with those of reported
for other systems (Table 3). Investigation of the results
shows that in view points of green reaction conditions, ef-
ciency, availability and amounts of nanocatalyst as well as
its reusability, the present protocol is more efcient or has a
comparable potentiality.
Although the exact mechanism of this synthetic protocol
is not clear, we think that a depicted mechanism (Scheme 4)
maybe plays a role in acetylation of amines with Ac2O.
According to this mechanism, the carbonyl group of acetic
anhydride is activated by coordination to Fe3O4/Cu MNPs.
Activated carbonyl then reacts with amine to give the cor-
responding N-acetamide.
Recycling of Fe3O4/Cu MNPs
For practical purposes, the ability to easily recycle the nano-
catalyst is highly desirable. To investigate this issue, the
reusability of Fe3O4/Cu MNPs was examined in acetylation
of aniline with acetic anhydride at the optimized conditions
(Table 1, entry 8). After completion of the reaction, the cop-
per nanocatalyst was separated from the reaction mixture
by an external magnet and was then washed with ethanol
to remove residual contaminants. The vessel of reaction
was again charged with fresh aniline, acetic anhydride and
H2O, and progress of the reaction was investigated in the
presence of recycled Fe3O4/Cu at 50 °C for a second time.
Fig. 2 XRD pattern of (a) Fe3O4 and (b) Fe3O4/Cu MNPs
optimize reaction conditions, progress of the reaction of ani-
line (1 mmol) with diferent amounts of acetic anhydride and
the copper nanocatalyst was investigated in H2O, MeOH,
EtOH, CH3CN, THF and CH2Cl2 (Table 1). Observation of
the results showed that H2O was the best solvent of choice
and using the molar equivalents of Ac2O:Fe3O4/Cu (1:0.05)
1 3

J IRAN CHEM SOC
Fig. 3 Magnetization curve
of (a) Fe3O4 and (b) Fe3O4/Cu
MNPs
Table 1 Optimization
Entry
Fe3O4/Cu
(mmol)
Ac2O
Solvent
(mL)
Temperature
(°C)
Time
(min)
Conversion (%)
experiments for acetylation of
aniline with Ac2O/Fe3O4/Cu
MNPs system under diferent
reaction conditions
(mmol)
1
2
3
4
5
6
7
8
–
1
1
1
0.5
0.2
0.1
0.05
0.1
0.1
0.1
0.1
0.1
2
2
2
1
1
1
1
1
1
1
1
1
1
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
CH2Cl2
MeOH
EtOH
CH3CN
THF
50
rt
120
120
2
3
3
3
3
3
120
120
120
120
120
5
90
50
50
50
50
50
50
50
50
50
50
50
100
100
100
100
100
100
40
40
40
0
30
9
10
11
12
13
All reactions were carried out with 1 mmol of aniline in 3 mL solvent
The examinations showed that the copper nanocatalyst can
be reused for 5 times without signifcant loss of its cata-
lytic activity (Fig. 4). The obtained results exhibited that
the nanocatalyst has remarkable reusability for the titled
transformation.
phenols were acetylated with the same reactivity by Ac2O/
Fe3O4/Cu system. The copper nanocatalyst was reused for 5
times without signifcant loss of its catalytic activity.
Experimental
Conclusion
Material and physical measurements
Magnetically recyclable nanocomposite of Fe3O4/Cu (with
22% Cu content) was prepared and then characterized by
SEM, XRD, ICP-OES and VSM analyses. The prepared
Fe3O4/Cu MNPs exhibited an excellent catalytic activity
toward acetylation of amines with Ac2O. All reactions were
carried out in H2O within 2–10 min to aford N-arylacet-
amides in 89–95% yields. Selective acetylation of amines
versus alcohols was carried out successfully. Amines and
All reagents and substrates were purchased from commer-
cial sources in high purity, and they were used without fur-
ther purifcation. 1H NMR and FTIR spectra were recorded
on Bruker Avance 300 MHz and Thermo Nicolet Nexus
670 FTIR spectrophotometer. All products are known, and
they were characterized by their 1H NMR and FTIR spec-
tra followed by comparison with authentic data. TLC was
applied for the purity determination of substrates, products
1 3

J IRAN CHEM SOC
Table 2 Acetylation of amines
with Ac2O/Fe3O4/Cu MNPs
system
Molar raꢀo
Subs./Ac2O/Cat. (min)
Time
Yield
(%)a
Entry
1
Substrate
Product
1:1:0.05
3
95
2
1:1:0.05
3
92
3
4
5
1:1:0.05
1:1:0.05
1:1:0.05
3
3
2
94
91
93
6
1:1:0.05
1:1:0.05
2
6
91
92
7
8
9
1:1:0.1
1:1:0.1
10
6
91
89
10
1:1:0.1
10
90
11
12
1:2:0.2
1:2:0.2
6
8
91
89
13
1:2:0.2
8
91
14
15
16
1:2:0.2
1:3:0.2
1:2:0.2
10
9
94
91
93
10
1 3

J IRAN CHEM SOC
Table 2 (continued)
All reactions were carried out in H2O (3 mL) at 50 °C
aYields refer to isolated pure products
Table 3 Comparison of the
Entry Catalyst
Conditions
Molar ratio
Catalyst
Time Yield References
(min) (%)
acetylation of aniline with Ac2O
catalyzed by diferent promoters
PhNH2/Ac2O amount
1
2
3
4
5
6
7
ZnAl2O4@SiO2
BiFeO3
NaHSO4·SiO2
(NH4)2.5H0.5PW12O40 Solvent‐free, rt 1:1
Gd(OTf)3
Cp2Zr(OPf)2
Fe3O4/Cu
Solvent‐free, rt 1:1
Solvent‐free, rt 1:1
10 mg
10 mg
10 mg
0.5 mol% 0.5
0.1 mol% 15
2 mol%
5 mol%
3
5
20
96
98
92
97
88
99
95
[12]
[13]
[14]
[15]
[16]
[17]
*
CH2Cl2, rt
1:1.2
CH3CN, rt
Solvent‐free, rt 1:1
H2O, 50 °C 1:1
1:1.5
10
3
* Present work
Scheme 4 A proposed mecha-
nism for acetylation of amines
with Ac2O/Fe3O4/Cu MNPs
system
and reaction monitoring over silica gel 60 F254 aluminum
sheet. Powder XRD was obtained by an X’PertPro Pana-
lytical, Holland difractometer in 40 kV and 30 mA with
a CuKα radiation (λ = 1.5418 Å), and the difraction pat-
terns were recorded in 2θ range (10°–80°). The particle
morphology was examined by measuring SEM using
FESEM–TESCAN MIRA3. The amounts of Cu, Fe and
O were measured by inductively coupled plasma-optical
emission spectrometry (ICP-OES, Varian 730-ES). Mag-
netic properties of the samples were determined using a
vibration sample magnetometer (VSM, model MDKFT)
under magnetic feld up to 20 kOe.
1 3

J IRAN CHEM SOC
added, and the mixture was stirred for 1 min under oil bath
conditions. Addition of Ac2O (1 mmol, 0.102 g) to the pre-
pared mixture was followed by stirring for 3 min at 50 °C.
After completion of the reaction, the copper nanocatalyst
was separated by an external magnet and the mixture was
extracted with EtOAc (3 × 8 mL). Organic layers were then
dried over anhydrous sodium sulfate. Evaporation of the sol-
vent under reduced pressure afords the pure acetanilide in
95% yield (0.128 g, Table 2, entry 1).
Acknowledgements The fnancial support of this work was gratefully
acknowledged by the Research Council of Urmia University.
Fig. 4 Acetylation of aniline with Ac2O and recycled Fe3O4/Cu
MNPs system
References
Preparation of Fe3O4 MNPs
1. J.R. Hanson, Protecting Groups in Organic Synthesis, 1st edn.
(Blackwell Science, Malden, 1999)
Nanoparticles of Fe3O4 were synthesized by a chemical co-
precipitation of chloride salts of Fe3+ and Fe2+ [39]. A solu-
tion of FeCl3·6H2O (5.838 g, 0.022 mol) and FeCl2·4H2O
(2.147 g, 0.011 mol) in distilled water (100 ml) was pre-
pared. The solution was stirred for 10 min at 85 °C under
N2 atmosphere. NH4OH (25%, 10 mL) was then added, and
magnetically recyclable nanoparticles of Fe3O4 were imme-
diately precipitated. The resulting mixture was continued to
be stirred at 85 °C for additional 30 min. The nanoparticles
were separated by an external magnet and washed with dis-
tilled water and then aq. NaCl (0.02 M). Drying under air
atmosphere afords the nanoparticles of magnetite.
2. P.G.M. Wuts, T.W. Greene, Greene’s Protective Groups in
Organic, 4th edn. (Wily, New York, 2006)
3. K.L. Chandra, P. Saravanan, R.K. Singh, V.K. Singh, Tetrahedron
58, 1369 (2002)
4. S.K. De, Tetrahedron Lett. 45, 2919 (2004)
5. A.K. Chakraborti, L. Sharma, R. Gulhane, Shivani, Tetrahedron
59, 7661 (2003)
6. A.K. Chakraborti, R. Gulhane, Chem. Commun. 1896 (2003)
7. K. Jeyakumar, D.K. Chand, J. Mol. Catal. A Chem. 255, 275
(2006)
8. Shivani, R. Gulhane, A.K. Chakraborti, J. Mol. Catal. A Chem.
264, 208 (2007)
9. A.K. Chakraborti, R. Gulhane, Tetrahedron Lett. 44, 3521 (2003)
10. A.K. Chakraborti, R. Gulhane, Tetrahedron Lett. 44, 6749 (2003)
11. K.J. Ratnam, R.S. Reddy, N.S. Sekhar, M.L. Kantam, F. Figueras,
J. Mol. Catal. A Chem. 276, 230 (2007)
A general procedure for preparation of Fe3O4/Cu
12. S. Farhadi, K. Jahanara, Chin. J. Catal. 35, 368 (2014)
13. S. Farhadi, M. Zaidi, J. Mol. Catal. A Chem. 299, 18 (2009)
14. B. Das, P. Thirupathi, J. Mol. Catal. A Chem. 269, 12 (2007)
15. J.R. Satam, R.V. Jayaram, Catal. Commun. 9, 2365 (2008)
16. R. Alleti, M. Perambuduru, S. Samantha, V. Prakash Reddy, J.
Mol. Catal. A Chem. 226, 57 (2005)
MNPs
To a solution of CuCl2·2H2O (0.402 g, 2.35 mmol) in
distilled water (30 mL), Fe3O4 MNPs (0.5 g, 2.16 mmol)
were added and the mixture was stirred for 30 min at room
temperature. To the prepared mixture, NaBH4 (0.177 g in
30 mL H2O) within 45 s (under N2 atmosphere) was added.
Upon the addition of NaBH4, a yellow–brown and then a
brown–black gelatinous particles of deposited copper on
magnetite, Fe3O4/Cu, were precipitated. The mixture was
continued to be stirred for 30 min under N2 atmosphere. The
obtained nanoparticles were then separated with an external
magnet and washed with deionized water (3 × 50 mL) fol-
lowed by drying under air atmosphere.
17. R. Qiu, Y. Zhu, X. Xu, Y. Li, L. Shao, X. Ren, X. Cai, D. An, S.
Yin, Catal. Commun. 10, 1889 (2009)
18. G. Sartori, R. Ballini, F. Bigi, G. Bosica, R. Maggi, P. Righi,
Chem. Rev. 104, 199 (2004)
19. A. Sakakura, K. Kawajiri, T. Ohkubo, Y. Kosugi, K. Ishihara, J.
Am. Chem. Soc. 129, 14775 (2007)
20. V. Polshettiwar, R. Luque, A. Fihri, H. Zhu, M. Bouhrara, J.-M.
Basset, Chem. Rev. 111, 3036 (2011)
21. V. Polshettiwar, R.S. Varma, Green Chem. 12, 743 (2010)
22. A. Maleki, RSC Adv. 4, 64169 (2014)
23. A. Maleki, R. Rahimi, S. Maleki, Synth. Met. 194, 11 (2014)
24. A. Maleki, R. Rahimi, S. Maleki, J. Iran. Chem. Soc. 12, 191
(2015)
25. A. Maleki, R. Rahimi, S. Maleki, Environ. Chem. Lett. 14, 195
(2016)
A general procedure for acetylation of arylamines
with Ac2O/F3O4/Cu MNPs system
26. A. Maleki, R. Paydar, React. Funct. Polym. 109, 120 (2016)
27. A. Maleki, M. Aghaei, R. Paydar, J. Iran. Chem. Soc. 14, 485
(2017)
In a round-bottom fask (10 mL) equipped with a mag-
netic stirrer, a mixture of PhNH2 (1 mmol, 0.093 g) and
H2O (3 mL) in oil bath (50 °C) was prepared. Magnetically
recyclable nanoparticles of Fe3O4/Cu (0.05 mmol) was then
28. A. Maleki, H. Movahed, P. Ravaghi, Carbohydr. Polym. 156, 259
(2017)
29. A. Maleki, M. Aghaei, H.R. Hafzi-Atabak, M. Ferdowsi, Ultra-
son. Sonochem. 37, 260 (2017)
1 3

J IRAN CHEM SOC
30. A. Maleki, M. Aghaei, Ultrason. Sonochem. 38, 115 (2017)
31. A. Maleki, S. Azadegan, Inorg. Nano-Met. Chem. 47, 917 (2017)
32. H.M.R. Gardimalla, D. Mandal, P.D. Stevens, M. Yen, Y. Gao,
Chem. Commun. 4432 (2005)
36. A. Nasirian, Int. J. Nano Dimens. 2, 159 (2012)
37. G.L. Li, Y.R. Jiang, K.L. Huang, P. Ding, I.I. Yao, J. Colloid
Interface Sci. A320, 11 (2008)
38. M. Nasrollahzadeh, S.M. Sajadi, Ceram. Int. 41, 14435 (2015)
39. X. Liu, Z. Ma, J. Xing, H. Liu, J. Magn. Magn. Mater. 270, 1
(2004)
33. P.D. Stevens, G.F. Li, J.D. Fan, M. Yen, Y. Gao, Chem. Commun.
4435 (2005)
34. V. Polshettiwar, R.S. Varma, Chem. Eur. J. 15, 1582 (2009)
35. P. Lignier, R. Bellabarba, R.P. Tooze, Chem. Soc. Rev. 41, 1708
(2012)
1 3