Magnetite (Fe3O4) nanoparticles-catalyzed Sonogashira- Hagihara reactions in ethylene glycol under ligand-free conditions

Article abstract of DOI:10.1002/adsc.201000390

A novel application of nanoparticles of paramagnetic magnetite (Fe ₃O₄) as an efficient catalyst for carbon-carbon bond formation via the Sonogashira-Hagihara reaction under heterogeneous ligand-free conditions in ethylene glycol (EG) is described. By using this catalyst, arylalkynes are produced from the reaction of aryl iodides and activated heteroaryl bromides with alkynes. The results are reproducible using the catalyst, which was prepared from different sources. The catalyst is easily separated by an external magnetic field from the reaction mixture. The separated catalyst can be recycled for several consecutive runs without appreciable loss of its catalytic activity.

Full text of DOI:10.1002/adsc.201000390

FULL PAPERS
DOI: 10.1002/adsc.201000390
Magnetite (Fe3O4) Nanoparticles-Catalyzed Sonogashira–
Hagihara Reactions in Ethylene Glycol under Ligand-Free
Conditions
Habib Firouzabadi,a,* Nasser Iranpoor,a,* Mohammad Gholinejad,a
and Jafar Hoseinib
a
Chemistry Department, College of Sciences, Shiraz University, Shiraz 71454, Iran
Fax : (+98)-711-228-0926; phone: (+98)-711-228-4822; e-mail: firouzabadi@chem.susc.ac.ir or iranpoor@chem.susc.ac.ir
Department of Chemistry, Yasouj University, Yasouj, 75918-74831, Iran
b
Received: May 18, 2010; Revised: November 10, 2010; Published online: December 30, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000390.
Abstract: A novel application of nanoparticles of from different sources. The catalyst is easily separat-
paramagnetic magnetite (Fe3O4) as an efficient cata- ed by an external magnetic field from the reaction
lyst for carbon-carbon bond formation via the Sono- mixture. The separated catalyst can be recycled for
gashira–Hagihara reaction under heterogeneous several consecutive runs without appreciable loss of
ligand-free conditions in ethylene glycol (EG) is des- its catalytic activity.
ACHTUNGTRENNUNGcribed. By using this catalyst, arylalkynes are pro-
duced from the reaction of aryl iodides and activated Keywords: ethylene glycol; iron oxide; magnetite
heteroaryl bromides with alkynes. The results are re- (Fe3O4); nanoparticles; Sonogashira–Higahara reac-
producible using the catalyst, which was prepared tion
Introduction
ferent preparations of iron salts are in readily found
in the literature and in addition, some of the iron
Transition metal salts play an important role as effi- complexes are commercially accessible. In spite of the
cient catalysts in organic reactions. In the last decade, aforementioned advantages, unexpectedly, in compar-
transition metal-catalyzed cross-coupling reactions ison with some other transition metals until lately,
have grown into an essential and highly important iron has been relatively ignored as a potential catalyst
class of reactions in modern organic chemistry.[1] In in the science of organic synthesis. However, in the
this line, group VIIIB metals demonstrate astonishing last few years, intensive attention has been paid to
effectiveness for the formation of carbon-carbon and iron as a catalyst for different organic transformations
carbon-heteroatom bonds by the reactions of organic such as hydrogenation,[5] oxidation,[6] epoxidation,[7]
electrophilic substrates with suitable nucleophiles. etc. In recent years, the search for catalysts other than
Over the past decades, enormous efforts have been the widely used palladium and nickel species for
committed to the reactions catalyzed by palladium- cross-coupling reactions has been under attention.
and nickel-based catalysts.[2] This huge effort has Along this line, immense efforts have started with the
somewhat laid down its shadows upon the reports of especial focus on the use of iron as catalyst. The re-
alternative metal complexes and metal-free protocols cently published articles by Furstner,[8] Knochel,[9] Na-
in this showground.[2] Toxicological features in paral- kamura and Bedford,[10] Cahiez,[11] Bolm,[12] and
lel with high prices related to utilizing palladium and others[13] all contain some of the examples for cross-
nickel catalysts have somewhat placed limitations on coupling protocols using cheap and non-toxic iron cat-
their general use for large-scale operations.[3]
alysts. However, iron salt/amine pre-catalysts have
In contrast, iron is one of the most plentiful metals been also used for organomagnesium reactants in
on our globe, and consequently, one of the most eco- large-scale carbon-carbon bond formation.[4]
nomical and environmentally well-suited ones.[4]
A new discussion by Buchwald and Bolm has
Moreover, iron is not toxic and additionally, many dif- raised a fundamental and interesting question about
Adv. Synth. Catal. 2011, 353, 125 – 132
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125

Habib Firouzabadi et al.
FULL PAPERS
the role of metal contaminants in FeCl3 when it is fields and their size-dependent evolution properties.
used as a catalyst for carbon-carbon and carbon-heter- They can have different heat capacity, vapour pres-
oatom bond formation in cross-coupling reactions.[12i] sure, melting point, and optical, magnetic and elec-
They have claimed, in their discussion, that the addi- tronic properties. Also owing to their high surface
tion of a trace amount of copper oxide to the reaction area, application of these particles as catalysts results
mixture has facilitated the cross-coupling reaction.
in a high concentration of reactive sites leading to
Since the olden times, magnetite with the chemical higher reactivity and selectivity.[15]
formula Fe3O4 has been engaged and recognized as a
permanent magnet. Because of the unique physical
properties of magnetite, in recent years, there is grow- Result and Discussion
ing interest in using magnetite as a privileged support
in organic synthesis.[14] Palladium and ruthenium sup- Now in this article, we want to report the use of nano-
ported on Fe3O4 are reported for the oxidation of al- particles of paramagnetic magnetite (Fe3O4) (<
cohols[14a–c] and a recoverable palladium-supported 30 nm) as an efficient catalyst for carbon-carbon bond
magnetite Fe3O4-ionic liquid catalyst for Suzuki– formation via the Sonogashira-Hagihara reaction
Miyaura and Heck-Mizoroki coupling reaction was under ligand-free conditions using ethylene glycol
also reported.[14d,e] Recently, Yus and co-workers have (EG) as a solvent and K2CO3 as a base (Scheme 1).
used impregnated copper on magnetite for the addi-
This nanocatalyst can be easily prepared from dif-
tion of alkoxydiboron reagents to C=C double bonds ferent chemical sources with reproducible results and
and for multicomponent preparations of propargyl- also its separation from the reaction mixture by an ex-
ACHTUNGTRENNUNG
amines.[14f,g] Direct coupling of sulfonamides and alco- ternal magnetic field is an easy task and not a time-
hols was also reported using a nano-Ru/Fe3O4 cata- consuming process. Use of Fe3O4 as a catalyst in or-
lyst.[14h]
ganic reactions is as yet limited to a few reports. Re-
Superparamagnetic nanoparticles of Fe3O4 have cently, the three-component coupling reaction of alde-
been extensively developed and studied for basic sci- hyde, alkyne and amine, the synthesis of a-amino ni-
entific considerations and also for manifold techno- triles catalyzed directly by nanoparticles of Fe3O4,
logical purposes.[15,16] All the technical and biomedical and intramolecular C N cross-coupling reactions cat-
À
applications require that the nanoparticles have high alyzed by nanoparticles of Fe3O4 were reported in the
magnetization values, a size smaller than 100 nm, and literature.[18] Also very recently magnetite nanoparti-
a narrow particle size distribution.[15]
cle-supported gel nanofibers have been used for the
The Sonogashira–Hagihara reaction is a rapidly Suzuki–Miyaura coupling reaction.[19]
rising protocol in organic synthesis, which results in In order to establish the reproducibility of the cata-
bond formation between C
(sp2) and C(sp) atoms by lyst, we have prepared the nanoparticles of Fe3O4 (<
AHCTUNGTRENNUNG
the catalysis of palladium in the presence or absence 30 nm) from three different sources according to the
of Cu(I) as a co-catalyst to produce arylalkynes and literature. For this purpose, a powder bulk sample of
conjugated enynes, which are important predecessors Fe3O4 (Sigma–Aldrich 99.99%) and another powder
for the preparation of natural products, pharmaceuti- bulk sample of Fe3O4 (Aldrich, 98%),[20] were em-
cals and useful organic materials.[17] Replacement of ployed for the preparation of the nanoparticles of
palladium with other transition metals, which are Fe3O4. In addition, the catalyst was prepared from the
more abundant and cheaper, for catalysis of this reac- reaction of Fe
2ACHTUNGTREN(UNG SO4)3·ACHTUNTGREN(NUGN H2O)X [Merck, contains 80%
tion is of concern for academia and industries. of Fe2A
CTHUNGTRENNUNG
A recent publication by Bolm et al. presents an last sample of the catalyst was prepared by the reac-
iron-catalyzed Sonogashira–Hagihara reaction using tion of FeCl2·4H2O with FeCl3·6H2O[21] (Merck
FeCl3/N,N-dimethylethylenediamine (dmeda) in tolu- >99%). The amounts of the contaminations of the
ene at 1358C.[12h] This is the first report regarding a produced Fe3O4 nanoparticles from the above sources
Sonogashira–Hagihara reaction catalyzed by an iron- with respect to Pd, Ni, Cu, and Co were determined
based catalyst. Moreover, in a subsequent publication, by ICP analysis. The results of the analysis are tabu-
the use of a similar catalytic system for the cross-cou-
pling reaction of terminal alkynes with vinyl iodides
was presented.[13b]
Easy and not time-consuming separation of the cat-
alysts from the reaction mixtures is a subject of inter-
est for investigation, especially for large-scale opera-
tion in industries. Moreover, in the past few years, at-
tention has been paid to the use of nanoparticles in
comparison with the corresponding bulk materials,
Scheme 1. Nanoparticles of Fe3O4: catalyzed Sonogashira–
Hagihara coupling reaction of aryl iodides and activated
because of their potential applications in a variety of heteroaryl bromides in ethylene glycol.
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Magnetite (Fe3O4) Nanoparticles-Catalyzed Sonogashira–Hagihara Reactions
Table 1. Contamination (ppb) of nanoparticles of Fe3O4 pre-
pared from different sources with respect to Pd, Cu, Ni and
Co.
Table 2. The effect of the addition of Pd, Cu, Ni and Co in
the reaction of 4-iodotoluene with phenylacetylene after
48 h.
Nano iron sources[a]
Pd
Cu
Ni
Co
Fe3O4 (A)
Fe3O4 (B)
Fe3O4 (C)
Fe3O4 (D)
450
485
416
850
34
45
63
3
80
95
239
65
440
448
764
563
Entry
Added metal
Pd(OAc)2 (1000 ppb)
NiCl2 (1000 ppb)
CuCl (1000 ppb)
CoCl2 (1000 ppb)
No addition
GC yield [%]
[a]
1
2
3
4
5
G
42
14
10
15
A: nanoparticles of Fe3O4 produced from bulk powder of
Fe3O4 (Sigma–Aldrich, 99.99%); B: nanoparticles of
Fe3O4 produced from bulk powder of Fe3O4 (Aldrich,
98%); C: nanoparticles of Fe3O4 produced from the reac-
<10
tion of Fe2ACHTUNGTRENNUNG(SO4)3·CAHTUNGTREN(NUNG H2O)X with FeSO4 (Merck, 80% and
99%, respectively); D: nanoparticles of Fe3O4 produced
from the reaction of FeCl2·4H2O and FeCl3·6H2O
(Merck, both 99%).
Table 3. Study of reaction of 4-iodotoluene with phenylace-
tylene in the presence of different ratios of Pd and Cu im-
purities and different amount of Fe3O4 nanoparticles.
lated in Table 1. Contamination of K2CO3 with re-
spect to the above-mentioned metals was also re-
solved to be Pd (130 ppb), Ni (45 ppb), Cu (24 ppb)
and Co (21 ppb). Moreover, the contamination of eth-
ylene glycol by Pd, Cu, Ni and Co has been also de-
termined by ICP analysis to be Pd (20 ppb), Cu (33
ppb), Ni (27 ppb) and Co (24 ppb).
In order to ascertain or negate the role of nanopar-
ticles of Fe3O4 as the catalyst and also the reproduci-
bility of the results, we have studied the reaction of 4-
iodotoluene with phenylacetylene as a model reaction
in the presence of the nanoparticles of Fe3O4 (pre-
pared from the abovementioned sources) using
K2CO3 as a base in ethylene glycol at 1258C. We no-
ticed that the desired arylalkyne was produced in 75–
88% yields. This observation shows that the catalyst,
which was prepared from different chemical sources,
gives reproducible results. However, for resolving the
effect of the size of the catalyst particles plus its es-
sentiality for the reaction, first the reaction of 4-iodo-
Entry Added metal
Concentration GC yield [%]
1
2
3
4
5
6
7
8
Pd
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
CuCl
CuCl
CuCl
Fe3O4 nanocatalyst 1 mol%
Fe3O4 nanocatalyst 2.5 mil%
Fe3O4 nanocatalyst 5 mol%
N
200 ppb
500 ppb
1000 ppb
1200 ppb
500 ppb
1000 ppb
1500 ppb
35
41
42
42
10
10
12
40
67
88
9
10
For demonstrating the major role of Fe3O4 nanopar-
toluene with phenylacetylene in the presence of the ticles as catalysts, we have studied the reaction of 4-
powder bulk Fe3O4 (Aldrich, 98%) under similar re- iodotoluene with phenylacetylene using different
action conditions was investigated. Under these con- ratios of Pd and Cu impurities and also by applying
ditions, the reaction proceeded sluggishly and the de- different ratios of Fe3O4 nanocatalyst. The results of
sired alkyne was produced in a low yield (40% GC) this study clearly confirm the role of Fe3O4 nanocata-
after 48 h. The similar reaction in the presence of lyst. Increasing or decreasing the amounts of Pd and
nanoparticles of Fe3O4 proceeded smoothly with ex- Cu impurities to the reaction mixture in the absence
cellent isolated yield (88–90%) of the desired product of the nanocatalyst did not affect the yield of the
after 48 h. Moreover, in the absence of the nanomag- product noticeably. The addition of different amounts
netite catalyst, the reaction was a low-yielding process of Pd to the reaction mixture resulted in the produc-
and the desired arylalkyne (GC) was produced in tion of the desired product in only 35-42% yields,
<8% after 48 h. Nevertheless, the effect of the sepa- whereas, the addition of extra amounts of Cu to the
rate addition of Pd, Ni, Cu and Co to the reaction mixture was even less effective and only 10–12% for-
mixture in the absence of the nanocatalyst was also mation of the desired product was observed. How-
studied. For this aim, Pd, Ni, Cu and Co as their salts
ACHTUNGTRENeNGNU ver, we have observed that the addition of different
(1000 ppb) were added independently to the reaction amounts of Fe3O4 nanocatalyst to the reaction mix-
mixture. The results of this investigation are tabulated ture affects the yield of the product noticeably. These
in Table 2.
results clearly show that Fe3O4 nanoparticles play a
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Table 4. Solvent screening for nanoparticles of paramagnetic
magnetite (Fe3O4) catalysis for the coupling reaction of io-
dobenzene with phenylacetylene in different solvents.
major role as catalysts for the reaction in spite of
their contamination with Pd and Cu impurities. The
results are shown in Table 3.
The effect of different solvents upon the reaction of
iodobenzene (1 mmol) with phenylacetylene (2 mmol)
as a model reaction in the presence of K2CO3
(2 mmol) and 5 mol% of the nanocatalyst (Fe3O4) at
1258C was studied (Table 4). The results show that
ethylene glycol (EG) is a suitable solvent for the reac-
tion. EG possesses negligible vapour pressure, is ther-
mally stable, is not so expensive with a low toxicity
(oral rat LD50: 4700 mgkgÀ1; skin rabbit LD50:
9530 mgkgÀ1).[22] Ethylene glycol is highly soluble in
water, and can be easily separated from the organic
phase by addition of water to the reaction mixture.
Entry
Solvent
Isolated yield [%]
1
2
3
4
5
DMF
NMP
EG
toluene
water
67
40
92
trace
trace
Table 5. Sonogashira-Hagihara coupling reactions of phenylacetylenes/alkynes with aryl iodides catalyzed by nanoparticles
of paramagnetic magnetite (Fe3O4) in ethylene glycol (EG) at 1258C.
Entry
1
ArI
Alkyne
Time [h]
35
Product
Isolated yield [%]
92
1a
2
3
60
40
1b
1c
90
82
4
5
6
48
30
28
1d
1e
1f
88
85
86
7
8
40
20
1g
1h
82[a]
86
9
45
1i
90
10
11
12
30
72
30
1j
1k
1l
91
76
79
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Magnetite (Fe3O4) Nanoparticles-Catalyzed Sonogashira–Hagihara Reactions
Table 5. (Continued)
Entry
ArI
Alkyne
Time [h]
72
Product
Isolated yield [%]
80
13
1m
14
15
72
30
1n
1d
76
90
16
17
18
42
35
48
1o
1p
1q
86
86
81
19
48
1r
78
[a]
This reaction shows the selectivity of the catalyst, which discriminates bromo from iodo compounds.
Evaporation of the aqueous phase results in reusable isolated yields, respectively (Table 5). In order to
EG for the subsequent reaction. EG can also be sepa- show the general applicability of the method, we have
rated from the reaction mixture by distillation. We also sudied the reaction of 1-octyne and 4-ethynyl-
have applied both procedures for the isolation and re-
ACHTUNGTRENtNUNG oluene with some aryl iodides. The reactions pro-
cycling of the solvent for the semi large-scale reaction ceeded well with high yields. The results are present-
of iodobenzene with phenylacetylene. In addition, we ed in Table 5, entries 15–19.
have also shown that the hydroxy groups in EG play
Comparison of the reactions of iodobenzene, 4-io-
a determinant role to improve the catalytic activity of donitrobenzene and 2-iodoanisole with phenylacety-
iron nanoparticles by stabilizing the lower oxidation lene catalyzed by Fe3O4 nanocatalyst and the FeCl3/
states of iron. For this statement, we have studied the N,N-dimethylethylenediamine system,[12h] shows that
model reaction (4-iodotoluene with phenylacetylene) the Fe3O4 nanocatalyst is a more efficient promoter as
in EG, which carries two hydroxy groups, 3-methoxy- tabulated in Table 6.
1-propanol, which has one hydroxy group, and 1,2-di-
Finally, the separation of the nano-particles of para-
methoxyethane without hydroxy groups.The results magnetic Fe3O4 is a highly simple process, which is
show that when the reaction was conducted in the sol- achieved by using a magnetic rod or by an external
vent with more hydroxy groups a higher yield of the electrically induced magnetic field as shown in
desired product is obtained. We were able to isolate Figure 1.
the enyne from EG in 85% whereas, from 3-methoxy-
Recyclability of the catalyst was tested upon the re-
1-propanol, and 1,2-dimethoxyethane, the desired action of iodobenzene with phenylacetylene in ethy-
product was isolated in 75 and 58% yields , respec-
tively
ACHTUNGTRENNUNG
Therefore, the subsequent reactions were per- the experimental errors for five successive runs as
formed in EG in which the coupling reactions of phe- presented in Table 7, Very lately, such a restoration of
nylacetylene with both electron-rich and electron-de- catalytic activity for nanoparticles of Fe3O4 has been
ficient aryl iodides furnished the desired enynes in also reported for the synthesis of a-amino nitriles,[18b]
76–90% isolated yields (Table 5). Nevertheless, in the propargylamines,[18c] and intramolecular C N cross-
À
presence of this catalyst, the reaction of phenyl bro- coupling reactions.[18d]
mide with phenylacetylene was very sluggish and the
Studies on other applications of this catalyst for the
unreacted substrates were observed by GC analysis. related Sonogashira–Hagihara reactions and also the
However, we observed that activated aryl bromides other carbon-carbon and carbon-heteroatom bond
such as 5-bromopyrimidine and 3-bromopyridine re- formation reactions are underway in our laboratories.
acted smoothly in the presence of this catalyst and
In conclusion, in this study we have presented a
the desired alkynes were obtained in 76% and 80% novel protocol in which paramagnetic nanoparticles
Adv. Synth. Catal. 2011, 353, 125 – 132
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Habib Firouzabadi et al.
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Table 6. Comparison between catalyst activity of FeCl3/N,N-
dimethylethylenediamine (dmeda) and Fe3O4 nanoparticles.
catalytic activity for several runs without markedly
observable signs for loss of its catalytic activity.
Entry ArX
Time [h] with
Fe3O4 (with
Isolated yield [%]
with Fe3O4 (with
FeCl3/dmeda)[12h] FeCl3/dmeda)[12h]
Experimental Section
Procedure for Preparation of Arylalkynes using
Fe3O4 Nanoparticles as Catalyst
1
2
3
35 (72)
40 (72)
60 (72)
92 (68)
82 (74)
76 (60)
To a 5-mL flask, which contained ethylene glycol (3 mL)
were added nanoparticales of magnetite (Fe3O4, 0.05 mmol,
11 mg), K2CO3 (2 mmol, 276 mg), aryl halide (1 mmol) and
phenylacetylene (2 mmol) and the mixture was heated at
1258C for the appropriate reaction times. The progress of
the reaction was monitored by TLC or GC. After comple-
tion of the reaction, the reaction mixture was extracted with
ethyl acetate or diethyl ether (5ꢁ1 mL) and the upper or-
ganic phase was separated and evaporated. Further purifica-
tion was performed by column chromatography (EtOAc/n-
hexane) to obtain the desired coupling product (Table 5).
Typical Procedure for Large-Scale Preparation of
Diphenylacetylene using Fe3O4 Nanoparticles as
Catalyst
The catalyst was easily employed for the large-scale opera-
tion. For this aim, the reaction of iodobenzene (30 mmol,
6.12 g) with phenylacetylene (60 mmol, 7.2 g) and the cata-
lyst (15 mmol, 3.48 g) under similar optimized reaction con-
ditions (see preceding paragraph). The reaction proceeded
well and the desired diphenylacetylene was obtained in a
high isolated yield after 40 h; yield: 4.5 g (86%) (Table 5,
entry 1).
Figure 1. a: Nanoparticles of paramagnetic Fe3O4 dispersed
in the reaction mixture at the beginning of the reaction, b:
accumulation of the nanoparticles of paramagnetic Fe3O4
around the magnetic bar after completion of the reaction,
and c: complete accumulation and separation of the catalyst
particles from the reaction mixture by the magnetic bar.
Table 7. Recycling of the Fe3O4 nanoparticle catalyst for the
reaction of iodobenzene with phenylacetylene.
Reaction of 4-Iodotoluene with Phenylacetylene in
the Presence of Different Ratios of Fe3O4
Nanocatalyst
Run
Time [h]
Isolated yield [%]
The reactions of 4-iodotoluene with phenylacetylene under
conditions mentioned in the preceding section with 5, 2.5
and 1 mol% of the catalyst were performed. Work up of the
reaction mixture after 48 h resulted the isolation of the de-
sired compound in 88, 67 and 40% yields, respectively
(Table 3, entries 8–10).
1
2
3
4
5
35
35
35
35
35
92
90
89
89
90
1a: 1H NMR (250 MHz, CDCl3): d=7.43–7.47 (m, 3H),
7.28–7.23 (m, 6H); 13C NMR (62.9 MHz, CDCl3): d=132.5,
128.3, 128.2, 123.2, 89.3.
of magnetite (Fe3O4) with the average size <30 nm
have been used as catalyst for the important Sonoga-
shira–Hagihara reaction in ethylene glycol (EG) using
aryl iodides and activated heteroaryl bromides with
1b: 1H NMR (250 MHz, CDCl3): d=7.37–7.43 (m, 4H),
7.22–7.25 (m, 3H), 6.79 (d, 2H, J=8.2), 3.73 (s, 3H);
13C NMR (100 MHz, CDCl3): d=159.6, 133.1, 131.5, 128.1
phenylacetylene. Our investigation shows that Fe3O4 128.0, 123.6, 115.4, 114.0, 89.5, 88.1, 55.3.
1c: 1H NMR (250 MHz, CDCl3): d=8.23–8.20 (m, 2H),
nanoparticles are responsible for the catalytic activi-
ties for the reactions investigated and presented in
this article, rather than its contamination with minute
amounts of Pd, Ni, Cu and Co. The reactions proceed-
ed in the air without any precautionary measures. The
catalyst functions under heterogeneous conditions
and its separation from the reaction mixture is easily
achieved by an external magnetic field, which is of in-
terest for large-scale operations for industrial purpos-
7.68–7.54 (m, 4H), 7.40–7.36 (m, 3H).
1d: 1H NMR (250 MHz, CDCl3): d=7.42–7.44 (m, 2H),
7.30–7.36 (m, 2H), 7.20–7.25 (m, 3H), 6.99–7.08 (m, 2H),
2.27 (s, 3H); 13C NMR (100 MHz, CDCl3): d=138.4, 131.6,
131.5, 129.1, 128.3, 128.1, 123.5, 120.2, 89.6, 88.8, 21.5.
1
1e: H NMR (250 MHz, CDCl3): d=7.41–6.88 (m, 8H).
1f: 1H NMR (250 MHz, CDCl3): d=7.48–7.43 (m, 8H),
7.30–7.26 (m, 6H).
1g: 1H NMR (250 MHz, CDCl3): d=7.44–7.37 (m, 4H),
es. The catalyst is also recyclable with retention of 7.31–7.24 (m, 5H).
130
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Adv. Synth. Catal. 2011, 353, 125 – 132

Magnetite (Fe3O4) Nanoparticles-Catalyzed Sonogashira–Hagihara Reactions
1h: 1H NMR (250 MHz, CDCl3): d=7.42–7.45 (m, 2H),
6.91–7.27 (m, 6H); 13C NMR (62.9 MHz, CDCl3): d=132.8,
131.7, 129.9, 129.3, 128.7, 128.5, 125.5, 123.3, 89.1, 84.7.
1i: 1H NMR (250 MHz, CDCl3): d=8.37–8.34 (m, 2H),
7.75–7.25 (m, 10H); 13C NMR (62.9 MHz, CDCl3): d=133.2,
131.7, 130.4, 129.1, 128.6, 128.4, 128.3, 128.0, 126.8, 126.4,
126.2, 125.3, 123.4, 120.9, 94.4, 87.6.
2003, 44, 5011–5013; e) N. E. Leadbeater, M. Marco, J.
Org. Chem. 2003, 68, 5660–5667; f) R. K. Arvela, N. E.
Leadbeater, J. Org. Chem. 2005, 70, 1786–1790;
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1j: 1H NMR (250 MHz, CDCl3): d=7.48–7.41 (m, 2H),
7.28–7.15 (m, 7H); 13C NMR (62.9 MHz, CDCl3): d=140.2,
131.8, 131.5, 129.5, 128.4, 128.3, 128.2 125.6, 123.5, 123.0,
93.4, 88.4, 20.8.
1k: 1H NMR (300 MHz, CDCl3): d=7.60–7.51 (m, 2H),
7.40–7.28 (m, 5H), 6.99–6.92 (m, 2H), 3.94 (s, 3H).
1l: 1H NMR (250 MHz, CDCl3): d=7.60–7.23 (7H, m),
6.74–6.71 (m, 2H), 5.20 (s, 1H).
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1m: H NMR (250 MHz, CDCl3): d=8.69 (s, 1H), 8.46–
8.47 (m, 1H), 7.71–7.74 (m, 1H), 7.45–7.51 (m, 2H), 7.31–
7.28 (m, 4H).
1
1n: H NMR (250 MHz, CDCl3): d=9.05 (s, 1H), 8.76 (s,
2H), 7.31–7.26 (m, 3H), 7.48–7.42 (m, 2H); 13C NMR
(62.9 MHz, CDCl3): d=158.5, 156.6, 131.2, 129.3, 128.5,
122.6, 119.8, 96.3, 82.3.
1o: 1H NMR (400 MHz, CDCl3): d=7.46–7.43 (m, 2H),
7.18–7.16 (m, 2H), 2.39 (s, 6H); 13C NMR (100 MHz,
CDCl3): d=138.1, 131.4, 129.0, 120.4, 88.8, 21.4.
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1p: 1H NMR (300 MHz, CDCl3): d=7.46–7.41 (m, 2H),
7.35–7.28 (m, 3H), 2.47–2.42 (m, 2H), 1.67–1.34 (m, 6H),
0.98–0.93 (m, 3H); 13C NMR (75 MHz, CDCl3): d=131.5,
128.1, 127.4, 124.0, 90.4, 80.5, 31.3, 28.7, 28.6, 22.5, 19.4, 14.0.
1q: 1H NMR (300 MHz, CDCl3): d=7.35–7.28 (m, 2H),
7.14–7.04 (m, 2H), 2.50–2.31ACTHNUGRTNEUNG(m, 5H), 1.64–1.34 (m, 8H),
0.98–0.93 (m, 3H); 13C NMR (75 MHz, CDCl3): d=137.3,
131.4, 128.9, 121.0, 89.6, 80.6, 31.4, 28.8, 28, 6, 22.6, 21.3,
19.4, 14.0.
1r:1H NMR (300 MHz, CDCl3): d=8.42–8.39 (m, 1H),
7.89–7.41 (m, 6H), 2.64–2.59 (m, 2H), 1.78–1.38 (m, 8H),
0.99–0.95 (m, 3H); 13C NMR (75 MHz, CDCl3): d=133.5,
133.2, 129.9, 128.2, 127.8, 126.4, 126.3, 126.2, 125.2, 121.8,
95.6, 78.6, 31.4, 28.9, 28.7, 22.6, 19.7, 14.1.
Acknowledgements
We gratefully acknowledge financial support of this work by
the Shiraz University Research Council. M.G. is thankful to
Professor Miguel Yus and Professor Rafael Chinchilla for
their helpful discussions and he also appreciates technical
help by Haythem Karim Dema.
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