Superparamagnetic copper ferrite nanoparticles as an efficient heterogeneous catalyst for the α-arylation of 1,3-diketones with C-C cleavage

Article abstract of DOI:10.1002/cctc.201300708

Superparamagnetic CuFe₂O₄ nanoparticles were synthesized from CuCl₂ and FeCl₃ by a co-precipitation method in ethylene glycol and characterized by several techniques, which included vibrating sample magnetometry, XRD, SEM, TEM, atomic absorption spectrometry, and nitrogen physisorption measurements. The CuFe ₂O₄ nanoparticles could be used as a solid catalyst for the α-arylation reaction of acetylacetone with iodobenzene to form phenylacetone as the principal product and 3-phenyl-2,4-pentanedione as the byproduct. The reaction that used the CuFe₂O₄ nanoparticles as catalyst could proceed to completion with 95 % selectivity to phenylacetone. The CuFe₂O₄ nanoparticles could be separated easily from the reaction mixture by magnetic decantation and could be reused several times for the α-arylation reaction without a significant degradation in catalytic activity. Magnetic attraction: Superparamagnetic CuFe₂O₄ nanoparticles are synthesized from CuCl ₂ and FeCl₃ by a co-precipitation method. The CuFe ₂O₄ nanoparticles are used as a solid catalyst for the α-arylation reaction of acetylacetone with iodobenzene to form phenylacetone as the principal product and 3-phenyl-2,4-pentanedione as the byproduct.

Full text of DOI:10.1002/cctc.201300708

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DOI: 10.1002/cctc.201300708
Superparamagnetic Copper Ferrite Nanoparticles as an
Efficient Heterogeneous Catalyst for the a-Arylation of
1,3-Diketones with CÀC Cleavage
Anh T. Nguyen, Lan T. M. Nguyen, Chung K. Nguyen, Thanh Truong, and Nam T. S. Phan*[a]
Superparamagnetic CuFe2O4 nanoparticles were synthesized
from CuCl2 and FeCl3 by a co-precipitation method in ethylene
glycol and characterized by several techniques, which included
vibrating sample magnetometry, XRD, SEM, TEM, atomic ab-
sorption spectrometry, and nitrogen physisorption measure-
ments. The CuFe2O4 nanoparticles could be used as a solid cat-
alyst for the a-arylation reaction of acetylacetone with iodo-
benzene to form phenylacetone as the principal product and
3-phenyl-2,4-pentanedione as the byproduct. The reaction that
used the CuFe2O4 nanoparticles as catalyst could proceed to
completion with 95% selectivity to phenylacetone. The
CuFe2O4 nanoparticles could be separated easily from the reac-
tion mixture by magnetic decantation and could be reused
several times for the a-arylation reaction without a significant
degradation in catalytic activity.
Introduction
The employment of heterogeneous catalysts to achieve facile
catalyst recovery and recycling as well as product separation is
a longstanding pursuit of catalysis science.[1] If the particle size
of the catalyst is decreased to nanometer scale, its activity
should be improved significantly.[2] However, in this case, the
separation of the nanoparticles from the reaction media still re-
mains a challenge.[3] This issue can be addressed by using su-
perparamagnetic nanoparticles as catalysts or catalyst sup-
ports, which facilitates catalyst separation from the liquid
phase with the application of an external magnetic field.[4] Re-
cently, superparamagnetic nanoparticles have been investigat-
ed intensively because of their numerous applications in syn-
thesis and catalysis. Indeed, superparamagnetic nanoparticles
have been utilized as catalyst supports for a variety of organic
transformations, such as the synthesis of 1,1-diacetates from al-
dehydes,[5] the synthesis of 1- and 5-substituted 1H-tetrazoles,[6]
the three-component coupling of aldehyde, alkyne, and
amine,[7] the synthesis of 3,4-dihydropyrimidin-2(1H)-ones by
the Biginelli reaction,[8] the asymmetric Friedel–Crafts alkylation
of N-substituted pyrroles with a,b-unsaturated aldehydes,[9]
and the synthesis of a library of spirooxindole-pyrimidine deriv-
atives by a three-component condensation reaction.[10] Unfunc-
tionalized CuFe2O4 superparamagnetic nanoparticles have
emerged as an efficient heterogeneous catalyst for the N-aryla-
tion of heterocycles with aryl halides,[11] the N-arylation of ni-
trogen nucleophiles,[12] the synthesis of diaryl thioether deriva-
tives from aryl halides and benzenethiol,[13] the cross-coupling
of thiols with aryl halides,[14] the deacetylation of carbohydrate
derivatives,[15] and the synthesis of 5-substituted 1H-tetrazoles
from nitriles and sodium azide.[16]
a-Aryl carbonyls have recently attracted significant attention
as versatile intermediates for the synthesis of several pharma-
ceutical candidates and agrochemicals as well as a variety of
biologically active natural products.[17,18] The development of
a general and efficient method for the formation of a CÀC
bond between an aromatic ring and the C atom positioned
a to a carbonyl group has remained a persistent challenge.[19]
Palucki and Buchwald[20] and Hamann and Hartwig[21] have
demonstrated new protocols for the homogeneous Pd-cata-
lyzed direct C-arylation of several ketones by using aryl halides
as electrophiles. However, the employment of homogeneous
Pd catalysts for organic transformations might suffer from
a number of drawbacks, such as high cost and difficulty in the
isolation and purification of the products.[19,22–24] Cu-based cat-
alysts have emerged recently as highly efficient alternatives to
the Pd systems because of the economic aspect as well as the
possibility for good functional-group tolerance.[17,25–29] Recently,
Lei and co-workers demonstrated the first example of the syn-
thesis of a-aryl ketones by using a simple Cu salt as the cata-
lyst without any ligands.[17] In view of green chemistry, the syn-
thesis of a-aryl carbonyls that uses heterogeneous Cu-based
catalysts should be targeted because of advantages in the
ease of handling, simple work-up, recyclability, and reusabili-
ty.[30] Furthermore, the facile catalyst separation also minimizes
the contamination of products with hazardous metals.[31,32] In
this work, we report the application of unfunctionalized
CuFe2O4 superparamagnetic nanoparticles as an efficient heter-
ogeneous catalyst for the Cu-catalyzed a-arylation of acetyl-
acetone with aryl iodides to form a-aryl carbonyls as the prin-
cipal products. The superparamagnetic catalyst could be isolat-
[a] A. T. Nguyen, L. T. M. Nguyen, C. K. Nguyen, Dr. T. Truong, Dr. N. T. S. Phan
Department of Chemical Engineering
HCMC University of Technology, VNU-HCM
268 Ly Thuong Kiet, District 10, Ho Chi Minh City (Viet Nam)
Fax: (+84)8-38637504
E-mail: ptsnam@hcmut.edu.vn
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201300708.
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ed easily from the reaction mixture by simple magnetic de-
cantation and could be reused several times without a signifi-
cant degradation in activity.
Results and Discussion
Catalyst synthesis and characterization
The superparamagnetic copper ferrite nanoparticles were syn-
thesized from CuCl2 and FeCl3 by a co-precipitation method in
ethylene glycol in the presence of NaOH as the base according
to a modified literature procedure.[33,34] The nanoparticles were
then characterized by using a variety of different techniques.
Elemental analysis of the nanoparticles by using atomic ab-
sorption spectrometry (AAS) gave 24.47% Cu and 45.60% Fe,
which corresponds to a Cu/Fe molar ratio of approximately 1:2
(Supporting Information). The magnetic properties of the
nanoparticles were investigated at room temperature by using
a vibrating sample magnetometer (VSM) with an applied field
from À15000 to 15000 Oe. The magnetization versus applied
field measurements confirmed that the as-synthesized copper
ferrite nanoparticles were superparamagnetic at room temper-
ature. Indeed, no hysteresis was observed, and the magnetiza-
tion curve should be completely reversible at room tempera-
ture (Figure 1). The saturation magnetization of the copper fer-
Figure 2. Powder X-ray diffractogram of the CuFe2O4 nanoparticles.
CPS=counts per second.
the CuFe2O4 nanoparticles, calculated from nitrogen adsorp-
tion–desorption isotherm data (Figure S1). Sun and co-workers
synthesized CuFe2O4 nanoparticles with a BET surface area of
26 m2 gÀ1.[12] Tasca and co-workers estimated a surface area of
40 m2 gÀ1 for CuFe2O4 nanoparticles.[15] However, Panda and
co-workers reported that BET surface areas of up to 216 m2 gÀ1
could be achieved for CuFe2O4 nanoparticles.[14] The pore size
distribution measurements of the CuFe2O4 nanoparticles re-
vealed a median pore width of 24 ꢁ, in which the pores of the
material could be formed among the ultrafine nanoparticles
within the aggregate (Figure S2). SEM (Figure S3) and TEM (Fig-
ure S4) images showed diameters of approximately 100 nm for
the CuFe2O4 nanoparticles. However, particle agglomeration
was observed clearly in the superparamagnetic nanoparticles,
and the primary particle size was likely closer to 5–10 nm in di-
ameter. Notably, most oxide particles, regardless of composi-
tion, aggregate on TEM grids, and TEM images do not imply
that the nanoparticles aggregate similarly if they are dispersed
in the liquid phase.[3]
Catalytic studies
The superparamagnetic CuFe2O4 nanoparticles were assessed
for their activity in the Cu-catalyzed a-arylation of acetylace-
tone with iodobenzene to form phenylacetone (A) as the prin-
cipal product and 3-phenyl-2,4-pentanedione (B) as the by-
product (Scheme 1). Initial studies addressed the effect of tem-
perature on the reaction conversion and the selectivity to the
phenylacetone. The reaction was performed in DMSO at an io-
Figure 1. Magnetization curves for the CuFe2O4 nanoparticles measured at
room temperature.
rite nanoparticles was found to be 49 emugÀ1, which was sig-
nificantly higher than that of other CuFe2O4 nanoparticles re-
ported previously.[12,14] This behavior confirmed that the as-
synthesized CuFe2O4 nanoparticles would be suitable for mag-
netic separation at room temperature, which facilitates easy
catalyst recovery and recycling as well as product separation.
XRD patterns of the superparamagnetic nanoparticles were
consistent with those reported previously, and no impurity
peaks were observed (Figure 2).[12,14,15] The diffraction of the
CuFe2O4 nanoparticles was in good agreement with the stan-
dard XRD pattern JCPDS 01-077-0010. BET and Langmuir sur-
face areas of 39 and 65 m2 gÀ1, respectively, were achieved for
Scheme 1. The a-arylation of acetylacetone with aryl iodides using the
CuFe2O4 nanoparticles as a solid catalyst.
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dobenzene/acetylacetone molar ratio of 1:3 with three equiva-
lents of K2CO3 as the base in the presence of 10 mol% CuFe2O4
nanoparticles as the catalyst at 100, 120, and 1408C. It was ob-
served that the a-arylation reaction could proceed readily at
1408C with more than 99% conversion achieved after 90 min.
A decrease of the temperature resulted in a dramatic decrease
in the reaction rate to afford 68 and 20% conversions after
180 min at 120 and 1008C, respectively. More important, the
temperature exhibited a significant effect on the reaction se-
lectivity to the phenylacetone. Experimental results indicated
that a selectivity of 95% to the a-arylated product with CÀC
cleavage was obtained after 180 min at 1408C, and 5%
3-phenyl-2,4-pentanedione was detected in the product mix-
ture by GC. A lower selectivity was observed for the reactions
performed at 120 and 1008C. A selectivity of 50% to phenyla-
cetone was observed for the reaction at 1208C, which left 50%
of the 3-phenyl-2,4-pentanedione in the reaction mixture after
180 min. As expected, the reaction performed at 1008C gave
60% 3-phenyl-2,4-pentanedione and 40% phenylacetone in
the reaction mixture after 180 min (Figure 3). This observation
could be explained based on the fact that the CÀC cleavage
process should be more favored at high temperature. Indeed,
the reaction temperature for the a-arylation of aryl halides
with active methylene compounds ranges from room tempera-
ture to 1408C, and a significantly longer reaction time was re-
quired for the reaction performed at lower temperature.[27,28]
For organic transformations that use solid catalysts, the
effect of the nature of the solvent on the reaction rate is of sig-
nificant importance. Therefore, we decided to investigate the
effect of the solvent on the reaction conversion and selectivity.
The a-arylation reaction was performed at 1408C with an iodo-
benzene/acetylacetone molar ratio of 1:3 and three equivalents
of K2CO3 as the base in the presence of 10 mol% CuFe2O4
nanoparticles as the catalyst in DMSO, DMF, and N,N-dimethy-
lacetamide (DMA) as the solvent. It was observed that the reac-
tion proceeded with difficulty in DMA, and 65% conversion
was detected after 180 min. DMF was more effective than
DMA and afforded 89% conversion after 180 min. The reaction
was also performed in p-xylene at reflux temperature (1388C).
However, the product was only observed in a trace amount
after 180 min. DMSO exhibited the best performance for the
reaction that used CuFe2O4 nanoparticles as the catalyst and
produced phenylacetone in a conversion of more than 99%
after 120 min. A selectivity of 95% to phenylacetone was ob-
served for the reaction performed in these three solvents
(Figure 4). Indeed, in the first example of the homogeneous
Figure 3. Effect of the reaction temperature on a) the reaction conversion
Figure 4. Effect of the solvent on a) the reaction conversion and b) the selec-
and b) the selectivity to phenylacetone.
tivity to phenylacetone.
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Cu-catalyzed a-arylation of aryl halides with active methylene
compounds, DMSO was the solvent of choice.[17] Similarly, Liu
and co-workers used Cu(OAc)2 and 1,1’-trimethylene-2,2’-bi-
imidazole ligand as a catalyst system for C-arylation reactions
in DMSO, DMF, THF, dioxane, and toluene and reported that
DMSO was the most suitable solvent for the transformation.[35]
DMSO also offered a better performance than N-methyl-2-pyr-
rolidone (NMP), dioxane, and toluene for the reaction of iodo-
benzene and ethyl acetoacetate that used CuI as the catalyst
in conjunction with ethylenediamine as the ligand.[36] However,
Xie and co-workers proposed DMF as an alternative solvent in-
stead of DCM, dioxane, THF, and acetone to improve selectivity
in similar reactions.[27]
catalyst was used, a conversion of 94% was achieved after
180 min. As expected, the increase of the catalyst concentra-
tion led to a significant enhancement in the reaction rate. The
reactions that used 5 and 7.5 mol% catalyst could proceed to
98% conversion after 180 min and 99% conversion after
150 min. More than 99% conversion was achieved for the reac-
tion after 120 min in the presence of 10 mol% catalyst. Lei and
co-workers obtained phenylacetone as the principal product
for the same reaction by using CuI as the catalyst,[17] whereas
Kidwai and co-workers obtained only 3-phenyl-2,4-pentane-
dione if CuO nanoparticles were used as the catalyst.[38] In this
work, we found that the catalyst concentration had a significant
effect on the reaction selectivity. However, phenylacetone was
the major product in all cases. Indeed, a selectivities of 83, 89,
90, and 95% to phenylacetone were observed for the reactions
that used 2.5, 5, 7.5, and 10 mol% CuFe2O4 nanoparticles as
the catalyst, respectively (Figure 5).
We then decided to investigate the effect of reagent molar
ratio on the reaction conversion and selectivity. The a-arylation
reaction was performed in DMSO at 1408C with three equiva-
lents of K2CO3 as the base in the presence of 10 mol% CuFe2O4
nanoparticles as the catalyst with iodobenzene/acetylacetone
molar ratios of 1:3, 1:2, and 1:1. It was observed that the
a-arylation reaction performed by using three equivalents of
acetylacetone could proceed readily under these conditions,
and more than 99% conversion was achieved after 120 min. As
expected, a decrease of the reagent ratio to 1:2 and 1:1 result-
ed in a decrease in the reaction rate with 96 and 91% conver-
sions, respectively, achieved after 180 min. It was also found
that the iodobenzene/acetylacetone molar ratio exhibited an
effect on the reaction selectivity. A selectivity of 95% to phe-
nylacetone was achieved after 180 min for the reaction that
used three equivalents of acetylacetone. However, the reaction
selectivity was reduced to 91% after 180 min for the reaction
performed with an iodobenzene/acetylacetone molar ratio of
1:2. The reaction that used one equivalent of acetylacetone of-
fered a lower selectivity with 86% phenylacetone and 14%
3-phenyl-2,4-pentanedione observed in the reaction mixture
(Figure S6). Indeed, in the first example of the achievement of
a-aryl ketones by using CuI as catalyst, Lei and co-workers also
employed three equivalents of acetylacetone for the reac-
tion.[17]
Several transition-metal-catalyzed organic transformations
required the presence of at least one equivalent of a base to
accelerate the transmetalation step in the catalytic cycle.[40]
A
variety of bases have been used for the C-arylation of carbonyl
compounds, such as NaOtBu,[19] Cs2CO3,[25,26,41] K3PO4,[29]
The catalyst concentration was also examined. Previously, in
several homogeneous Cu-catalyzed C-arylations of carbonyl
compounds, 10 mol% catalyst was employed. Jiang and co-
workers used 10 mol% CuI in conjunction with 20 mol% l-pro-
line as a catalyst system,[37] whereas Kidwai and co-workers
performed the reaction in the presence of 10 mol% CuO nano-
particles.[38] In the first example of the homogeneous Cu-cata-
lyzed a-arylation of aryl halides with active methylene com-
pounds to form a-aryl carbonyls, a Cu concentration of
10 mol% was employed.[17] In some other C-arylations, the Cu
catalyst concentration required for the reaction could be up to
20 mol%.[26,27] Notably, the Pd-catalyzed C-arylation of carbonyl
compounds required only 2 mol% catalyst concentration.[39]
Therefore, we decided to investigate the effect of catalyst con-
centration on the reaction conversion and selectivity. The a-ar-
ylation reaction was performed in DMSO at 1408C with an io-
dobenzene/acetylacetone molar ratio of 1:3 and three equiva-
lents of K2CO3 as the base in the presence of 2.5, 5, 7.5, and
10 mol% CuFe2O4 nanoparticles as the catalyst. If 2.5 mol%
Figure 5. Effect of the catalyst concentration on a) the reaction conversion
and b) the selectivity to phenylacetone.
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NaOH,[27] NaH,[42] K2CO3,[36,37] and triethylamine.[35] In the first ex-
ample of the homogeneous Cu-catalyzed a-arylation of aryl
halides with active methylene compounds, Lei and co-workers
reported that the reaction proceeded readily in the presence
of K3PO4 as the base.[17] Therefore, we decided to investigate
the effect of different bases on the a-arylation of acetylacetone
with iodobenzene by using the CuFe2O4 nanoparticles as the
catalyst with K3PO4, K2CO3, Cs2CO3 and CH3COONa as the base
for the reaction. The a-arylation reaction was performed in
DMSO at 1408C with an iodobenzene/acetylacetone molar
ratio of 1:3 in the presence of 10 mol% CuFe2O4 nanoparticles
as catalyst and three equivalents of the base. If we used K3PO4
as the base for the reaction, 94% conversion was achieved
after 180 min. K2CO3 exhibited a better performance for the re-
action, and more than 99% conversion was achieved after
120 min. CH3COONa was not suitable for the a-arylation of
acetylacetone that used CuFe2O4 nanoparticles as the catalyst.
It was observed that the reaction that used Cs2CO3 could
afford more than 99% conversion after 120 min. Moreover, a se-
lectivity of 95% to phenylacetone was observed after 180 min
for the reactions that used Cs2CO3 or K2CO3, whereas 89% se-
lectivity was detected if K3PO4 was used (Figure 6). However,
because of its low availability and high cost, Cs2CO3 should
only be used if there was a significant difference compared to
other bases.
Previously, several C-arylation reactions were performed in
the presence of different amounts of base, and it was reported
that the base concentration could exhibit a significant impact
on both the reaction conversion and selectivity.[25,36,38,43] Hen-
nessy and Buchwald performed the Cu-catalyzed arylation of
diethyl malonate in the presence of 1.5 equivalents of Cs2CO3
and achieved only the product without CÀC cleavage.[25] Simi-
larly, Kidwai and co-workers reported that only 3-phenyl-2,4-
pentanedione was detected for the Cu-catalyzed C-arylation of
acetylacetone that used 0.5 equivalents of Cs2CO3.[38] Zeevaart
and co-workers performed the Cu-catalyzed C-arylation reac-
tion between ethyl acetoacetate and aryl halides by using dif-
ferent amounts of K2CO3 and pointed out that the selectivity
to the C-arylated product with CÀC cleavage was favored at
a high concentration of the base.[36] Lei and co-workers report-
ed that the reaction proceeded readily in the presence of
three equivalents of K3PO4 as the base.[17] Moreover, the base
concentration also had a significant effect on the Pd-catalyzed
a-arylation of carbonyl compounds with aryl halides.[43] To in-
vestigate the effect of the base concentration on the reaction
conversion and selectivity, the a-arylation reaction was per-
formed in DMSO at 1408C with an iodobenzene/acetylacetone
molar ratio of 1:3 in the presence of 10 mol% CuFe2O4 nano-
particles as the catalyst by using one, two, and three equiva-
lents of K2CO3 as the base, respectively. We found that the re-
action that used one equivalent of K2CO3 could proceed to
92% conversion after 180 min. However, a selectivity of only
52% to phenylacetone was detected after 180 min, which left
48% of 3-phenyl-2,4-pentanedione in the product mixture. An
increase of the amount of K2CO3 led to a significant enhance-
ment in both the conversion and the selectivity of the reaction.
More than 99% conversion was observed after 150 min for the
Figure 6. Effect of the base on a) the reaction conversion and b) the selectiv-
ity to phenylacetone.
reaction that used two equivalents of K2CO3, although only
87% selectivity to phenylacetone was obtained after 180 min.
Our experimental results indicated that three equivalents of
K2CO3 should be used for the a-arylation using CuFe2O4 nano-
particles as the catalyst (Figure S7).
The catalytic activity of the CuFe2O4 nanoparticles in the Cu-
catalyzed a-arylation of acetylacetone with iodobenzene to
form phenylacetone was also compared to that of other salts,
which included CuI, CuCl2, FeCl3, Pd(OAc)2, and a mixture of
CuCl2 and FeCl3 (molar ratio of 1:2). The reactions were per-
formed in DMSO at 1408C with an iodobenzene/acetylacetone
molar ratio of 1:3 in the presence of 10 mol% catalyst and
three equivalents of K2CO3 as the base. As expected, the reac-
tion that used 10 mol% CuI as the catalyst could proceed to
more than 99% after 150 min. Indeed, 10 mol% CuI was em-
ployed as the catalyst in the first example of the homogeneous
Cu-catalyzed a-arylation of aryl halides with active methylene
compounds to form a-aryl carbonyls.[17] CuCl2 was an excellent
homogeneous catalyst for the a-arylation reaction, and more
than 99% conversion was achieved after 120 min. The use of
a mixture of CuCl2 and FeCl3 also offered more than 99% con-
version after 120 min. However, a similar reaction rate was ob-
served compared to that of CuCl2. Notably, FeCl3 exhibited no
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reactivity for the reaction, and not even trace amounts of
product were detected by GC. The a-arylation reaction did not
occur in the presence of Pd(OAc)2. Pd(OAc)2 in conjunction
with suitable ligands could offer high catalytic activity for the
Pd-catalyzed C-arylation of carbonyl compounds with aryl hal-
ides.[39] Similarly, ꢂzdemir and co-workers also reported that
ligands should be used in the C-arylation of carbonyl com-
pounds using Pd(OAc)2 as catalyst.[41] The CuFe2O4 nanoparti-
cles exhibited a similar activity as CuI and CuCl2, and more
than 99% conversion was obtained after 120 min (Figure 7).
ease of handling, simple work-up, recyclability, and reusability,
superparamagnetic nanoparticles could minimize the differ-
ence in the reaction rate of homogeneous and heterogeneous
reactions because of the catalyst particle sizes.
For organic transformations that use solid catalysts in the
liquid phase, an important issue is the possibility that some
active sites could migrate from the solid phase into the reac-
tion solution, and that these leached species could contribute
significantly to the catalytic activity.[3] To determine if leaching
was a problem in the Cu-catalyzed a-arylation of acetylacetone
with iodobenzene with CuFe2O4 nanoparticles as the catalyst,
an experiment was performed to estimate the contribution of
leached active Cu species to the catalytic activity. The reaction
was performed in DMSO at 1408C with an iodobenzene/acetyl-
acetone molar ratio of 1:3 in the presence of 10 mol% CuFe2O4
nanoparticles as the catalyst and three equivalents of K2CO3 as
the base. After 180 min, the CuFe2O4 nanoparticles were sepa-
rated from the reaction mixture by magnetic decantation. The
reaction solution was transferred to a new reactor vessel, and
fresh reagents were added to the solution. The resulting mix-
ture was stirred for 180 min at 1408C, and aliquots were with-
drawn at different time intervals for analysis by GC. No further
conversion was detected for the reaction after the CuFe2O4
nanoparticles were removed. This observation proved that
there was no contribution from leached active Cu species and
that conversion was only possible in the presence of the
CuFe2O4 nanoparticles (Figure 8). However, further investiga-
tions are needed to elucidate the real active species in the Cu-
catalyzed a-arylation reaction that uses this catalyst system.
The use of solid catalysts for organic transformations should
be targeted as they offer several advantages, which include
easy catalyst separation, recovery, and recycling. It is expected
that the solid catalyst can be separated easily from the reac-
tion mixture, recovered, and reused several times before it
eventually deactivates completely. Indeed, it was reported pre-
viously that high activity and high selectivity were achieved in
several homogeneous Cu-catalyzed a-arylation reactions. How-
Figure 7. Effect of different catalysts on a) the reaction conversion and
b) the selectivity to phenylacetone.
The experimental data were consistent with a previous report
in which homogeneous CuI and CuII catalysts afforded similar
results.[17] Mechanistically, in the presence of base, CuII can be
reduced to CuI and participate in the catalytic cycle. Further-
more, in arylation reactions that use aryl iodides, CuIII, which
can be generated from CuI or CuII, is often proposed as a cata-
lytically active species.[44–46]
With respect to homogeneity, the purification of products
contaminated with transition metals is often problematic if ho-
mogeneous catalysts are used.[47] This issue further increases
the cost of the process and limits their industrial applications,
especially in pharmaceutical processes. In comparison with
other heterogeneous catalysts, along with advantages in the
Figure 8. Leaching test indicated no contribution from the homogeneous
catalysis of active Cu species leached into the reaction solution.
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ever, these homogeneous catalysts could not be recycled and
reused.[17,26,27,36] Therefore, we decided to investigate the re-
coverability and reusability of the CuFe2O4 nanoparticles as the
catalyst in the a-arylation reaction by separating the nanoparti-
cles repeatedly from the reaction mixture by magnetic decant-
ation, washing them, and then reusing them. The reaction was
performed in DMSO at 1408C with an iodobenzene/acetylace-
tone molar ratio of 1:3 in the presence of 10 mol% CuFe2O4
nanoparticles as the catalyst and three equivalents of K2CO3 as
the base. After each run, an external magnetic field was ap-
plied to the outer surface of the glass reaction vessel that con-
tained the CuFe2O4 nanoparticles by using a small permanent
magnet. The reaction solution was then removed easily from
the reaction vessel by decantation while the external magnet
held the superparamagnetic nanoparticles stationary inside the
vessel. The catalyst was washed several times with copious
amounts of deionized water, ethanol and diethyl ether by
magnetic decantation, dried under vacuum at 1408C for
180 min, and reused in further reactions under identical condi-
tions to those of the first run. It was found that the CuFe2O4
nanoparticles could be recovered and reused several times for
the a-arylation reaction without a significant degradation in
catalytic activity. A conversion of 97% was still achieved after
180 min in the sixth run. As expected, a selectivity of 95% to
phenylacetone was achieved after 180 min in the sixth run
(Figure 9). To confirm the recoverability and reusability of the
of the CuFe2O4 nanoparticles as catalyst, which included iodo-
benzene, 4-iodotoluene, 4-iodoanisole, and 4’-iodoacetophe-
none. The reaction was performed in DMSO at 1408C with an
aryl iodide/acetylacetone molar ratio of 1:3 in the presence of
10 mol% CuFe2O4 nanoparticles as the catalyst and three
equivalents of K2CO3 as the base. Aliquots were withdrawn at
different time intervals and analyzed by GC to indicate the dif-
ference in the reaction rate by using these aryl halides. It was
found that the electronic effects of the substituents present in
the aryl iodide structure exhibited a significant impact on the
a-arylation reaction that used the CuFe2O4 nanoparticles as the
catalyst. The presence of an electron-donating group on the
benzene ring (i.e., 4-iodotoluene and 4-iodoanisole) resulted in
a decrease of the reaction rate, although more than 99% con-
version was still obtained after 180 min in the case of 4-iodoto-
luene and 4-iodoanisole. As expected, a higher reaction rate
was observed for the case of the aryl iodide with an electron-
withdrawing substituent (i.e., 4’-iodoacetophenone). The a-ary-
lation reaction of 4’-iodoacetophenone with acetylacetone
could afford more than 99% conversion after 90 min. These re-
sults confirm that electron-donating groups slow the reaction
down, whereas electron-withdrawing substituents accelerate
the a-arylation transformation. Furthermore, the a-arylation re-
action of acetylacetone with 4-iodoacetophenone showed
98% selectivity to phenylacetone after 180 min, whereas 95%
selectivity was detected for the other aryl iodides (Figure 10).
Conversely, Parkinson and co-workers reported that the a-ary-
lation of 4-iodoanisole with ethyl acetoacetate offered a higher
selectivity to the product with CÀC cleavage than the case of
iodobenzene and 4’-iodoacetophenone.[36] Lei and co-workers
reported that aryl iodides that bear either electron-donating or
electron-withdrawing substitutents could react smoothly with
acetylacetone in the presence of CuI catalyst to afford the de-
sired products with high yields.[17] However, further investiga-
tions are necessary to elucidate the mechanism of the a-aryla-
tion reaction that uses CuFe2O4 nanoparticles as the catalyst.
From a practical viewpoint, a 15 mmol scale reaction of 4-io-
doanisole with acetoacetone was conducted. The result was
comparable to that of the small-scale (1 mmol) reaction, and
greater than 90% conversion was obtained in 3 h. The product
was isolated in 78% yield and characterized by 1H and
13C NMR spectroscopy (Supporting Information). This com-
pound is known.[17]
Figure 9. Catalyst recycling study.
CuFe2O4 nanoparticles as the catalyst in the a-arylation reac-
tion, kinetic data were also recorded. Kinetic studies indicated
that the catalytic activity of the nanoparticles decreased slight-
ly after each use, although the selectivity remained almost un-
changed (Figure S8). Indeed, stable activity cannot be con-
firmed by reporting only similar reaction conversions after
long reaction times. Kinetic studies should be the true test of
catalyst deactivation. Furthermore, the XRD pattern of the
reused nanoparticles after the sixth run indicated that the crys-
tallinity of the catalyst was maintained during the course of
the reaction, and only a slight difference in the overall struc-
ture was observed for the reused CuFe2O4 nanoparticles (Fig-
ure S9).
Conclusions
CuFe2O4 superparamagnetic nanoparticles were synthesized
and characterized by vibrating sample magnetometry, XRD,
SEM, TEM, atomic absorption spectrometry, and nitrogen phys-
isorption measurements. The CuFe2O4 nanoparticles could be
used as a solid catalyst for the Cu-catalyzed a-arylation of ace-
tylacetone and iodobenzenes to form phenylacetone as the
principal product and 3-phenyl-2,4-pentanedione as the by-
product. The optimal conditions employed 5% CuFe2O4 cata-
lyst, DMSO solvent, and K2CO3 base (3 equivalents) at 1408C in
3 h with a 3:1 iodoarene/acetoacetone molar ratio. The recov-
ery of the catalyst was achieved easily by simple magnetic de-
The investigation was then extended to the a-arylation reac-
tion of acetylacetone with different aryl iodides in the presence
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(2.206 g, 8 mmol) were added to a round-bottomed flask that con-
tained ethylene glycol (120 mL). The mixture was stirred magneti-
cally at RT for 40 min to achieve a clear solution. NaOH (1.6667 g,
40 mmol) was then added to the solution with stirring at RT, which
caused a color change. The resulting mixture was stirred magneti-
cally at RT for 2 h. After that, the reaction temperature was in-
creased over 2 h to 190–2008C and kept constant for 10 h. The re-
action mixture was cooled naturally to RT, and the particles were
recovered by using a magnet. The final product was washed sever-
al times with copious amounts of deionized water and ethanol fol-
lowed by magnetic decantation and dried under vacuum at 2008C
for 6 h to yield the CuFe2O4 superparamagnetic nanoparticles
(0.56 g).
Catalytic studies
The CuFe2O4 superparamagnetic nanoparticles were used as a cata-
lyst for the Cu-catalyzed a-arylation of acetylacetone with aryl io-
dides to form a-aryl carbonyls. In a typical experiment, a predeter-
mined amount of the catalyst was added to a flask that contained
a
solution of iodobenzene (0.11 mL, 1 mmol), acetylacetone
(0.31 mL, 3 mmol), K2CO3 (0.4188 g, 3 mmol), and n-hexadecane
(0.20 mL) as internal standard in DMSO (10 mL). The catalyst con-
centration was calculated based on the molar ratio of Cu/iodoben-
zene. The reaction mixture was stirred at 1408C under an Ar at-
mosphere for 180 min. The reaction conversion was monitored by
withdrawing aliquots from the reaction mixture at different time
intervals, quenching with deionized water (1 mL), extracting with
diethylether (2ꢃ2 mL), drying over anhydrous Na2SO4, and analysis
by GC with reference to n-hexadecane. Further product identity
was confirmed by GC–MS. To investigate the recyclability of the
catalyst, the reaction solution was removed from the reaction
vessel by decantation while the external magnet held the super-
paramagnetic nanoparticles stationary inside the vessel. The cata-
lyst was washed several times with copious amounts of deionized
water, ethanol, and diethyl ether by magnetic decantation, dried
under vacuum at 1408C for 180 min, and reused if necessary. For
the leaching test, after the reaction, the catalyst was separated
from the reaction mixture by magnetic decantation. The reaction
solution was transferred to a new reactor vessel, and fresh re-
agents were added to the solution. The resulting mixture was
stirred for 180 min at 1408C, and aliquots were withdrawn at differ-
ent time intervals for analysis by GC.
Figure 10. Effect of different aryl iodides on a) the reaction conversion and
b) the reaction selectivity.
cantation. The reaction could proceed to completion with 95%
selectivity to phenylacetone. The CuFe2O4 nanoparticles could
be reused several times for the a-arylation reaction without
a significant degradation in catalytic activity. The a-arylation re-
action could only proceed in the presence of the solid CuFe2O4
nanoparticles, and no contribution from leached active copper
species, if any, was detected. Our results demonstrate the feasi-
bility of the application of the CuFe2O4 superparamagnetic
nanoparticles as a catalyst for several organic transformations.
The superparamagnetic properties of the CuFe2O4 nanoparti-
cles offer potential advantages over conventional catalysts in
terms of catalyst recovery and recyclability and would be of in-
terest to the chemical industry.
Acknowledgements
The Department of Science and Technology–Ho Chi Minh City is
acknowledged for financial support through contract number 45/
2013/HD–KHCN–VU (351/2013/HD–SKHCN).
Keywords: copper · heterogeneous catalysis · iron · magnetic
properties · nanoparticles
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Revised: September 15, 2013
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