Polystyrene-anchored palladium(II) schiff base complex: A reusable catalyst for phosphine-free and copper-free sonogashira cross-coupling reaction in aqueous medium

Article abstract of DOI:10.1080/00397911.2010.515331

A novel polystyrene-supported palladium(II) complex, an excellent and recyclable catalyst, was synthesized for Sonogashira reactions. The present complex shows high catalytic activity for Sonogashira cross-coupling reaction of aryl halides with phenylacetylene under phosphine-free and copper-free reaction conditions in aqueous (DMF-H₂O)medium.The catalyst could be reused for at least six reaction cycles with almost unchanged catalytic properties. Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397911.2010.515331

This article was downloaded by: [University of Glasgow]
On: 20 May 2013, At: 02:36
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Polystyrene-Anchored Palladium(II)
Schiff Base Complex: A Reusable Catalyst
for Phosphine-Free and Copper-Free
Sonogashira Cross-Coupling Reaction in
Aqueous Medium
Manirul Islam a , P. Mondal a , A. Singha Roy a , K. Tuhina b , S.
Mondal a & D. Hossain a
a Department of Chemistry, University of Kalyani, Nadia, India
b Department of Chemistry, B.S. College, Danapur, India
Published online: 29 Jun 2011.
To cite this article: Manirul Islam , P. Mondal , A. Singha Roy , K. Tuhina , S. Mondal & D. Hossain
(2011): Polystyrene-Anchored Palladium(II) Schiff Base Complex: A Reusable Catalyst for Phosphine-
Free and Copper-Free Sonogashira Cross-Coupling Reaction in Aqueous Medium, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:17, 2583-2593
To link to this article: http://dx.doi.org/10.1080/00397911.2010.515331
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,

demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 2583–2593, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.515331
POLYSTYRENE-ANCHORED PALLADIUM(II) SCHIFF
BASE COMPLEX: A REUSABLE CATALYST FOR
PHOSPHINE-FREE AND COPPER-FREE SONOGASHIRA
CROSS-COUPLING REACTION IN AQUEOUS MEDIUM
Manirul Islam,1 P. Mondal,1 A. Singha Roy,1 K. Tuhina,2
S. Mondal,1 and D. Hossain1
1Department of Chemistry, University of Kalyani, Nadia, India
2Department of Chemistry, B.S. College, Danapur, India
GRAPHICAL ABSTRACT
Abstract A novel polystyrene-supported palladium(II) complex, an excellent and recyclable
catalyst, was synthesized for Sonogashira reactions. The present complex shows high catalytic
activity for Sonogashira cross-coupling reaction of aryl halides with phenylacetylene under
phosphine-freeandcopper-freereactionconditionsinaqueous(DMF–H2O)medium. Thecata-
lyst could be reused for at least six reaction cycles with almost unchanged catalytic properties.
Keywords Aqueous medium; aryl halides; palladium(II) complex; Sonogashira
cross-coupling
INTRODUCTION
Palladium-catalyzed reactions have been recognized as powerful tools in mul-
tiple organic transformations.[1–5] Despite the remarkable utility of Pd catalysts in
organic synthesis, they suffer from one significant drawback: They often remain in
the organic products at the end of the reaction. In recent years, the search for envir-
onmentally benign chemical processes or methodologies has received much attention
from chemists, because they are essential for the conservation of the global ecosys-
tem. Homogeneous palladium–catalyst system suffers from a major drawback in
that the catalyst recovery and=or its reuse is difficult, affecting the overall economics
of the process.[6–8] Heterogeneous catalysts, which are widely used in industry, have
good thermal stability, can be easily separated from the reaction mixture, and often
can be regenerated and reused. Therefore, heterogenizing homogeneous metal
Received February 22, 2010.
Address correspondence to Dr. Manirul Islam, Department of Chemistry, University of Kalyani,
Kalyani, Nadia, 741235, W.B., India. E-mail: manir65@rediffmail.com
2583

2584
M. ISLAM ET AL.
complex by supporting it on an insoluble support has attracted a lot of interest as a
suitable method for solving many practical problems, including recovery of the cata-
lyst from the reaction mixture and recycling. Palladium supported on materials such
as carbon,[9] amorphous silicates,[10] polymers,[11] and zeolites[12] is commonly
employed in heterogeneous catalysis.
The palladium-catalyzed coupling of terminal acetylenes with aryl and vinyl
halides (Sonogashira reaction) is one of the important and widely used carbon–carbon
bond-forming reactions in organic synthesis.[13–19] The most commonly used catalytic
systems for this transformation include PPh3 as ligand together with CuI as the coca-
talyst. The main disadvantages of the palladium catalysts containing simple phosphine
ligands is of high cost of phosphine, air- and thermosensitivity, low activity toward
deactivated substrates, and contamination of the products with the phosphine-based
by-products. The presence of copper iodide in the reaction mixture also has several
drawbacks: Oxidative homocoupling of acetylenes (Glaser-type reaction) cannot be
avoided in a copper-mediated reaction,[20,21] in which by-products (diaryldiacetylenes)
are generally difficult to separate from the desired products, and copper acetylide is a
potentially explosive reagent. Use of water as a reaction medium for transition-metal-
catalyzed reactions is very attractive for organic synthesis because water is a readily
available, safe, and environmentally friendly solvent. In water or water–organic sol-
vent mixtures, the Sonogashira reaction is very effectively catalyzed by palladium cata-
lyst containing no copper salt and=or phosphine ligands.[22–28]
Herein, we have reported a truly heterogeneous palladium catalyst for the
Sonogashira cross-coupling reactions in aqueous medium under copper-free and
phosphine-free reaction conditions. The catalyst shows good catalytic activity in
the coupling reactions of various aryl halides with phenylacetylene. Furthermore,
easy catalyst recovery and excellent recycling efficiency of the catalyst make it an
ideal system for coupling reactions in the aqueous phase.
The synthesis of the polymer-anchored Schiff base palladium(II) catalyst is illu-
strated in Scheme 1. It was readily prepared through a two-step procedure. The poly-
styrene amine (1 g) was reacted with benzaldehyde (3 mL) in dry toluene (10 mL)
under reflux conditions for 72 h to afford polymer Schiff base ligand (2). This poly-
mer Schiff base ligand (1 g) subsequently reacted with palladium acetate (0.5 g) in
acetic acid (10 mL) at 80 ꢀC for 10 h to generate the corresponding polystyrene-
supported palladium(II) catalyst.
Scheme 1. Synthesis of polymer-anchored Pd(II) Schiff base complex.

SONOGASHIRA CROSS-COUPLING REACTION
2585
Because of insolubility of the polymer-anchored Pd(II) complex in all common
organic solvents, its structural investigations was limited only to its physicochemical
properties, SEM-EDX, TGA-DTA, infrared (IR), and ultraviolet-visible (UV-vis)
spectral data. The complete incorporation of the organic substructure in the material
was confirmed by elemental analysis. The metal content of polymer anchored Pd(II)
complex determined by atomic absorption spectrometry (AAS) suggested 2.23 wt%
metal loading in the immobilized palladium complex. The SEM images of
polymer-anchored ligand and metal complex clearly show the morphological change
that occurred on the surface of the polymer matrix after loading of the metal (Fig. 1).
EDX data also support the metal attachment on the surface of polymer matrix
(Fig. 2).
The catalyst is thermally stable up to 250 ꢀC. The IR spectrum of polymer-
anchored Schiff base ligand showed characteristic IR peak at 1635 cmꢁ1, which
=
may be assigned to the -C N stretching vibration of imine which on complexation
with metal shifted toward lower frequency to 1615 cmꢁ1. This suggested bond forma-
tion between Pd and ligand. Other characteristic peaks at 1585 cmꢁ1, 1430 cmꢁ1
(n COO bridged), 720 cmꢁ1 (orthometallation),[29] and 455 cmꢁ1 (n Pd-N)[30] also
support the formation of the palladium(II) complex. The UV-vis spectra provided
further evidence for the presence of palladium(II) on polymer support. The absorp-
tion maxima at 295 nm may be attributed to the p!pꢂ transition in polymer and
phenyl moiety, and the absorption at higher range (370–440 nm) may be due to
the p!pꢂ and n!pꢂ transitions of imine system in conjugation with the aromatic
nuclei.
In our previous study of cross-coupling reactions, it was found that the present
catalyst is highly efficient for the Suzuki cross-coupling reaction, which furnished
biaryl products with good yields.[31] Therefore, continuing the search for further
catalytic reactions, we decided to investigate the catalytic activity of the present cata-
lyst for the Sonogashira reaction. We began our investigation of the Sonogashira
coupling reaction with the present catalyst using the coupling of bromobenzene with
phenylacetylene as a model reaction (Scheme 2). Because the performance of a suc-
cessful metal-catalyzed cross-coupling reaction is known to be governed by a number
=
Figure 1. FE SEM image of polymer-anchored Schiff base ligand (A) and PS-[(C6H4CH N)Pd(OAc)]2
complex (B).

2586
M. ISLAM ET AL.
=
Figure 2. EDX spectrum of PS-[(C6H4CH N)Pd(OAc)]2 complex.
of factors, at first the effects of various bases, solvents, temperatures, and catalyst
concentrations on the Sonogashira cross-coupling reaction were surveyed. Using
tetrabutylammonium bromide (TBAB) as an additive enhanced the rate of the
reaction. All the reactions were carried out under an air atmosphere.
We first examined the effect of reaction temperature on the Sonogashira coup-
ling reaction. The results are reported in Table 1. At room temperature, very poor
yield of the cross-coupled product was obtained. As expected, raising the tempera-
ture substantially increased the conversion of bromobenzene, and a temperature
of 70 ꢀC provided the greatest conversion. The reaction was carried out under an
air atmosphere.
To verify the solvent effect in Sonogashira coupling reactions, we have inves-
tigated a series of reactions by taking the model reaction in different solvents
(Table 1). The results showed that the nonpolar solvents such as toluene or p-xylene
gave moderate to low amount of conversions (entries 5 and 6). Quantitative yields
were observed with polar solvents such as dimethylsulfoxide (DMSO), dimethylfor-
manide (DMF), or methanol (entries 7–9). The catalytic activity was also observed in
neat water, and the desired product was obtained in 70% yields. The reaction per-
formed in DMF–H2O (1:1) was found to be the best for the present catalytic system
Scheme 2. Sonogashira reaction of phenylacetylene with bromobenzene.

SONOGASHIRA CROSS-COUPLING REACTION
2587
Table 1. Optimal conditions for polymer-anchored Pd(II) Schiff base complex–catalyzed Sonogashira
reaction of bromobenzene and phenylacetylenea
Base–substrate
ratio
Entry Temperature (ꢀC)
Solvent
Base
Time (h)
Yield (%)
1
2
30
50
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
p-xylene
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
K2CO3
K3PO4
NaOH
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
0.5:1
1:1
12
12
12
12
24
24
12
12
12
12
12
12
12
24
12
12
Trace
23
3
60
70
75
97
4
5
120
110
100
100
70
22
14
6
Toluene
DMF
7
87
79
8
DMSO
Methanol
H2O
9
76
70
10
11
12
13
14
15
16
70
70
DMF–H2O (1:1)
DMF–H2O (1:1)
DMF–H2O (1:1)
69
57
70
70
34
No reaction
70
70
DMF–H2O (1:1) No base
DMF–H2O (1:1)
DMF–H2O (1:1)
Et3N
Et3N
26
32
70
aReaction conditions: bromobenzene (1.0 mmol), phenylacetylene (2.0 mmol), catalyst (1.0 mol% Pd),
and solvent (6 mL). Yields determined by GC analysis.
(entry 4), as the greatest conversion was obtained in this mixed aqueous–organic
solvent.
The base usually plays an important role in the Sonogashira cross-coupling
reaction. Thus, different kinds of bases were screened, and the results are summar-
ized in Table 1. From the results, it is seen that triethylamine is the most effective
base in the present catalytic system. Inorganic bases are less effective and gave mod-
erate yield of the coupled product. No conversion was observed in the absence of
base. The effect of base substrate ratios on the coupling reaction was also examined.
Using a base–substrate molar ratio of 2:1, the greatest conversion of bromobenzene
was obtained.
We next evaluated the catalytic activity of the present catalyst using a variety
of aryl halides under optimized reaction conditions, and the results obtained were
collected as shown in Table 2. From the results, it is seen that the reaction was effec-
tive in the presence of a wide variety of functional groups on the aryl iodides, bro-
mides, and chlorides, giving good to excellent conversions to the corresponding
products. Electron-poor aryl halides were coupled with phenylacetylene efficiently
in the presence of catalyst. The electron-rich arylhalides also afford moderate to
good conversions. The electronically neutral iodo and bromobenzene produced a
large amount of the desired product when coupled with phenylacetylene. The
ortho-substituted aryl halide, 2-bromotoluene, gave good yields of coupled product
but requires longer reaction times, which might be due to steric hindrance. Under the
same reaction conditions, heteroaryl bromide such as 2-bromopyridine furnished the
desired coupled product in good yields. In addition, 1-bromonaphthalene was suc-
cessfully coupled with phenylacetylene to afford the corresponding coupled product
in 89% yields. The less reactive chlorobenzene showed low conversion. The activated

2588
M. ISLAM ET AL.
Table 2. Sonogashira cross-coupling reaction of aryl halides with phenylacetylene with polymer-anchored
Schiff base complex catalysta
Entry
ArX
Time (h)
Productb (no.)
Conv.c (%) Isolated yield (%)
1
2
3
4
5
6
7
8
9
8
12
8
100
100
100
96
100
100
99
8
95
12
12
12
12
12
95
95
88
87
92
92
98
98
99
99
10
11
24
12
87
89
83
88
12
15
91
89
13
14
24
24
42
71
42
70
aReaction conditions: aryl halide (1.0 mmol), phenylacetylene (2.0 mmol), catalyst (1.0 mol% Pd), Et3N
(2.0 mmol), TBAB (1.0 mmol), and DMF–H2O (1:1, 6 mL) at 70 ꢀC.
bProducts were identified by comparison of their GC-MS and 1H NMR spectral data with those
reported in the literature.
cConversion of reactant was determined by GC and GCMS analysis using dodecane as internal
standard.
aryl chloride, 4-chloroacetophenone, gave the corresponding coupled product in
moderate yields. However, in both reactions high temperature and longer reaction
time were required.

SONOGASHIRA CROSS-COUPLING REACTION
2589
The main advantage of the present polymer-anchored Pd(II) Schiff base complex
catalyst for the Sonogashira coupling compared to previous literature reports[11,32] is
that it achieves good yields and selectivity of Sonogashira coupling products in the
absence of toxic copper salt and expensive phosphine ligands. The reaction was carried
out in an aqueous medium in open air instead of an inert atmosphere.
To determine whether the catalyst is actually functioning in a heterogeneous
manner, a hot-filtration test was performed for the Sonogashira coupling reaction
of bromobenzene and phenylacetylene. During the reaction, the solid catalyst was
separated from the reaction mixture by filtration after 4 h of reaction, and the
determined conversion was 55%. The obtained filtrate was continually stirred
under the same reaction conditions for a further 3 h. The gas chromatographic
analysis showed no increase in the conversion. Atomic absorption spectrometric
analysis of the filtrate confirms that no metal is present. These results confirm
that no leaching of the metal from the catalyst takes place during the catalytic
reaction.
The lifetime is an important point concerning the use of the catalyst both for
industrial and pharmaceutical applications. As the solid catalyst can be recovered
easily from the reaction mixture, we examined the reuse of the present catalyst using
the reaction of bromobenzene and phenylacetylene. The capability of recycling the
polymer-anchored Pd(II) Schiff base complex was confirmed after six consecutive
reactions in DMF–H2O (1:1) medium. After the first run, the catalyst was separated
by filtration, washed thoroughly, dried under vacuum, and then subjected to the next
run under the same reaction conditions. The results summarized in Fig. 3 demon-
strate that there was almost no change in catalytic activity even after the sixth
run. The metal content of the recycled catalyst remained almost unaltered, indicating
no leaching of the metal from the polymer support.
=
Figure 3. Recycling activity of PS-[(C6H4CH N)Pd(OAc)]2 complex catalyst toward the Sonogashira
cross-coupling reaction of bromobenzene with phenylacetylene. Reaction conditions: bromobenzene
(1.0 mmol), phenylacetylene (2.0 mmol), catalyst (1.0 mol% Pd), Et3N (2.0 mmol), TBAB (1.0 mmol),
and DMF–H2O (1:1, 6 mL) at 70 ꢀC.

2590
M. ISLAM ET AL.
In conclusion, we have developed a mild copper-free Sonogashira coupling
reaction of arylhalides and acetylene in aqueous medium (DMF–H2O, 1:1) using
Et3N as base under aerobic conditions using polymer-anchored Schiff base complex
catalyst. The main advantages associated with this catalyst are (i) easy preparation
and handling of the catalyst and commercial availablility of the support; (ii) no need
for copper salt and phosphine ligand in the catalytic system; and (iii) excellent yield
and selectivity in an aqueous medium. Easy product recovery and the recycling
efficiency, along with high selectivity of this catalyst, may be useful for the synthesis
of different fine chemicals under ecofriendly conditions.
EXPERIMENTAL
The reagents and solvents were obtained from commercial sources and were
generally used without further purification. Poly(styrene-co-divinyl benzene) and
palladium acetate were supplied by Aldrich Chemical Company, USA, and other
organic reagents were purchased from Merck.
Surface morphology and particle size of the samples were analyzed using a
scanning electron microscope (Zeiss EVO40, England) equipped with EDX facility.
Thermogravimetric analysis (TGA) of the immobilized catalyst was determined
using a Mettler Toledo TGA 851. The Fourier transform (FT–IR) spectra were
recorded on a Perkin-Elmer FTIR 783 spectrophotometer using KBr pellets. Diffuse
reflectance UV-vis spectra were taken using a Shimadzu UV-2401PC doubled-beam
spectrophotometer having an integrating sphere attachment for solid samples. A
Perkin-Elmer 2400C elemental analyzer was used to collect microanalytical data
(C, H, and N). Palladium content in the catalyst was determined using Varian
1
AA240 atomic absorption spectrophotometer. The H NMR spectra were recorded
on 250-, 300-, or 500-MHz spectrometers. The chemical shifts were measured in
parts per million (ppm), using tetramethylsilane (TMS) as an internal standard
and CDCl3 as the solvent.
General Procedure for the Conduct of Sonogashira Cross-Coupling
Reaction in DMF–H2O (1:1) Medium
To a suspension of the polymeric Pd(II) catalyst (1.0 mol% of Pd) in DMF–
H2O (6.0 mL, 1:1), aryl halides (1.0 mmol), phenylacetylene (2.0 mmol), TBAB
(1.0 mmol), triethylamine (2.0 mmol), and n-dodecane (15–20 mg) as an internal
gas chromatography (GC) standard were added. The resulting mixture was stirred
at the prearranged temperature for the appropriate reaction time. Samples were
withdrawn periodically and analyzed by GC. GC yield was determined using
n-dodecane as an internal standard and based on the amount of aryl halide
employed. After completion of the reaction, the reaction mixture was cooled to room
temperature and extracted with Et2O three times. The organic phase in the combined
filtrates was separated and dried over Na2SO4. The solvent was evaporated under
reduced pressure, and the crude material was purified by flash column chromato-
graphy on silica gel. The product was analyzed by GC-MS and 1H NMR. All
prepared compounds were known and compared with authentic samples.

SONOGASHIRA CROSS-COUPLING REACTION
2591
Sonogashira Coupling Products
Diphenylacetylene (2a). White solid, mp: 54ꢀC (lit. mp[33] 54–55 ꢀC). 1H NMR
(CDCl3, 300 MHz): d (ppm) 7.75–7.52 (m, 4H), 7.36–7.33 (m,6H). GC-MS: m=z 178.
1-Acetyl-4-phenylethynyl-benzene (2b). Pale yellow solid, mp: 98–99 ꢀC
1
(lit. mp[34] 97 ꢀC). H NMR (CDCl3; 250 MHz): d (ppm) 7.93 (d, 2H,), 7.62–7.54
(m, 4H), 7.38–7.35 (m, 3H), 2.60 (s, 3H). GC-MS: m=z 220.
4-Phenylethynyl-toluene (2c). White solid, mp: 70–72 ꢀC (lit. mp[35]
1
72–73 ꢀC). H NMR (CDCl3, 300 MHz): d (ppm) 7.55–7.52 (m, 2H), 7.44 (d, 2H),
7.36–7.32 (m, 3H), 7.16 (d, 2H), 2.38 (s, 3H). GC-MS: m=z 192.
1-Methoxy-4-phenylethynyl-benzene (2d). Pale yellow solid, mp: 59–60ꢀC
1
(lit. mp[36] 59–60 ꢀC). H NMR (CDCl3, 300 MHz): d (ppm) 7.55–7.48 (m, 4H),
7.37–7.33 (m, 3H), 6.90 (d, 2H), 3.83 (s, 3H), GC-MS: m=z 208.
1-Cyano-4-phenylethynyl-benzene (2e). White solid; mp 105–106ꢀC (lit.
1
mp[28] 106–108 ꢀC). H NMR (300 MHz, CDCl3): d 7.36–7.39 (m, 3H), 7.52–7.59
(m, 2H), 7.61–7.62 (m, 4H); GC-MS: m=z 203.
1-Nitro-4-phenylethynyl-benzene (2f). Yellow solid, mp: 119 ꢀC (lit. mp[36]
119–120 ꢀC). 1H NMR (CDCl3, 300 MHz): d (ppm) 7.38–7.40 (m, 3H), 7.54–7.58 (m,
2H), 7.65 (d, 2H), 8.21(d, 2H); GC-MS: m=z 223.
1
1-Phenylethynyl-toluene (2g). White solid. H NMR (CDCl3, 500 MHz): d
(ppm)7.44–7.39 (m,3H), 7.25–7.21 (m, 3H), 7.12–7.10 (m, 2H), 7.08–7.04 (m,1H),
2.41 (s, 3H). GC-MS: m=z 192.
1
2-Phenylethynyl-pyridine (2h). Yellow oil. H NMR (CDCl3, 250 MHz): d
(ppm) 8.55 (d, 1H), 7.64–7.54 (m, 3H), 7.50 (d, 1H), 7.34–7.29 (m, 3H), 7.22–7.14
(m, 1H). GC-MS: m=z 179.
1-(1-Naphthyl)-2-phenylacetylene (2i). Yellow oil. 1H NMR (CDCl3,
500 MHz): d (ppm) 8.44 (d, 1H), 7.83 (ddd, 2H), 7.75 (d, 1H), 7.64 (d, 2H), 7.58
(t, 1H), 7.52 (t, 1H), 7.44 (t, 1H), 7.39–7.34 (m, 3H). GC-MS: m=z 228.
ACKNOWLEDGMENTS
We gratefully acknowledge the Department of Science and Technology (DST),
the Council of Scientific and Industrial Research (CSIR), and the University Grant
Commission (UGC), New Delhi, India, for funding. One of the authors, K. T., is
thankful to the UGC (eastern region), India, for financial support. We also thank
the DST and UGC, New Delhi, India, for providing instrumental support under
the Funding for Infrastructure in Science and Technoloy (FIST) and SAP program.
REFERENCES
1. Tsuji, J. Palladium Reagents and Catalysts; Wiley: Chichester: New York, 1995.
2. Malleron, J. L.; Fiaud, J. C.; Legros, J. Y. Handbook of Palladium-Catalyzed Organic
Reactions; Academic Press: London, 1997.

2592
M. ISLAM ET AL.
3. Diederich, F.; Stang, P. J. Metal-Catalyzed Cross-coupling Reactions; Wiley-VCH:
Weinheim, 1999.
4. Negishi, E.; de Meijere, A. Handbook of Organopalladium Chemistry for Organic
Synthesis; Wiley-Interscience: New York, 2002.
5. Yin, L.; Liebscher, J. Carbon–carbon coupling reactions catalyzed by heterogeneous
palladium catalysts. Chem. Rev. 2007, 107, 133–173.
6. Guan, J. T.; Weng, T. Q.; Yu, G. A.; Liu, S. H. Copper-free PdCl2=PPh3-catalyzed
Sonogashira coupling reaction of aryl bromides with terminal alkynes in water.
Tetrahedron Lett. 2007, 48, 7129–7133.
7. Bhattacharya, S.; Sengupta, S. Palladium-catalyzed alkynylation of aryl halides
(Sonogashira reaction) in water. Tetrahedron Lett. 2004, 45, 8733–8736.
8. Bakherad, M.; Keivanloo, A.; Bahramian, B.; Hashemi, M. Copper-free Sonogashira
coupling reactions catalyzed by a water-soluble Pd–salen complex under aerobic
conditions. Tetrahedron Lett. 2009, 50, 1557–1559.
9. Novak, Z.; Szabo, A.; Repasi, J.; Kotschy, A. Sonogashira coupling of aryl halides
catalyzed by palladium on charcoal. J. Org. Chem. 2003, 68, 3327–3329.
10. Polshettiwar, V.; Len, C.; Fihri, A. Silica-supported palladium: Sustainable catalysts for
cross-coupling reactions. Coord. Chem. Rev. 2009, 253, 2599–2626.
11. Kim, J. H.; Lee, D. H.; Jun, B. H.; Lee, Y. S. Copper-free Sonogashira cross–coupling
reaction catalyzed by polymer-supported N-heterocyclic carbene palladium complex.
Tetrahedron Lett. 2007, 48, 7079–7084.
12. Djakovitch, L.; Rollet, P. Sonogashira cross-coupling reactions catalysed by copper-free
palladium zeolites. Adv. Synth. Catal. 2004, 346, 1782–1792.
13. Sonogashira, K.; Tohda, Y.; Hagihara, N. A convenient synthesis of acetylenes: Catalytic
substitutions of acetylenic hydrogen with bromoalkenes, iodoarenes, and bromopyridines.
Tetrahedron Lett. 1975, 16, 4467–4470.
14. Sonogashira, K.; Yatake, T.; Tohda, Y.; Takahashi, S.; Hagihara, N. Novel preparation
of r-alkynyl complexes of transition metals by copper(I) iodide–catalysed dehydrohalo-
genation. J. Chem. Soc., Chem. Commun. 1977, 291–292.
15. Takahashi, S.; Kuroyama, Y.; Sonogashira, K.; Hagihara, N. A convenient synthesis of
ethynylarenes and diethynylarenes. Synthesis 1980, 627–630.
16. Siemsen, P.; Livingston, R. C.; Diederich, F. Acetylenic coupling: A powerful tool in
molecular construction. Angew. Chem., Int. Ed. 2000, 39, 2632–2657.
´
17. Chinchilla, R.; Najera, C. The Sonogashira reaction: A booming methodology in
synthetic organic chemistry. Chem. Rev. 2007, 107, 874–922.
18. Tykwinski, R. R. Evolution in the palladium-catalyzed cross-coupling of sp- and sp2-
hybridized carbon atoms. Angew. Chem., Int. Ed. 2003, 42, 1566–1568.
19. Negishi, E.; Anastasia, L. Palladium-catalyzed alkynylation. Chem. Rev. 2003, 103, 1979–
2017.
20. Siemsen, P.; Livingston, R. C.; Diederich, F. Acetylenic coupling: A powerful tool in mol-
ecular construction. Angew. Chem., Int. Ed. Engl. 2000, 39, 2632–2657.
21. Hay, A. S. Oxidative coupling of acetylenes, II. J. Org. Chem. 1962, 27, 3320–3321.
22. Ye, Z. W.; Yi, W. B. Polymer-supported palladium perfluorooctanesulfonate [Pd(OPf)2]:
A recyclable and ligand-free palladium catalyst for copper-free Sonogashira coupling
reaction in water under aerobic conditions. J. Fluorine Chem. 2008, 129, 1124–1128.
´
´
23. Gil-Molto, J.; Karlstro¨m, S.; Najera, C. Di(2-pyridyl)methylamine–palladium dichloride
complex covalently anchored to a styrene-maleic anhydride co-polymer as recoverable
catalyst for C–C cross-coupling reactions in water. Tetrahedron 2005, 61, 12168–12176.
24. Liang, B.; Huang, M.-W.; You, Z.-J.; Xiong, Z.-C.; Lu, K.; Fathi, R.; Chen, J.-H.;
Yang, Z. Pd-catalyzed copper-free carbonylative Sonogashira reaction of aryl iodides with

SONOGASHIRA CROSS-COUPLING REACTION
2593
alkynes for the synthesis of alkynyl ketones and flavones by using water as a solvent.
J. Org. Chem. 2005, 70, 6097–6100.
25. Thathagar, M. B.; Rothenberg, G. One-pot Pd=C-catalyzed ‘‘domino’’ HALEX and
Sonogashira reactions: A ligand- and Cu-free alternative. Org. Biomol. Chem. 2006, 4,
111–115.
26. Djakovitch, L.; Rollet, P. Sonogashira cross-coupling reactions catalyzed by hetero-
geneous copper-free Pd-zeolites. Tetrahedron Lett. 2004, 45, 1367–1370.
27. Kim, J. H.; Lee, D. H.; Jun, B. H.; Lee, Y. S. Copper-free Sonogashira cross–coupling
reaction catalyzed by polymer-supported N-heterocyclic carbene palladium complex.
Tetrahedron Lett. 2007, 48, 7079–7084.
28. Sotiriou-Leventis, C.; Wang, X.; Mulik, S.; Thangavel, A.; Leventis, N. Immobilization of
Pd catalysts on mesoporous silica for amine- and copper-free Sonogashira coupling
reactions. Synth. Commun. 2008, 38, 2285–2298.
29. Onue, H.; Moritani, I. Ortho-Metalation reactions of N-phenylbenzaldimine and its
related compounds by palladium(II) acetate. J. Organomet. Chem. 1972, 43, 431–436.
30. Durig, J. R.; Layton, R.; Sink, D. W.; Mitchell, B. R. Far infrared spectra of palladium
compounds, I: The influence of ligands upon the palladium chloride stretching frequency.
Spectrochim. Acta 1965, 21, 1367–1378.
31. Islam, S. M.; Mondal, P.; Singha Roy, A.; Mondal, S.; Mobarak, M. An effcient and reu-
sable polymer-supported palladium catalyst for the Suzuki cross-coupling reactions of
aryl halides. J. Chem. Res. 2009, 756–760.
32. Polshettiwar, V.; Hesemann, P.; Moreau, J. J. E. Palladium containing nanostructured sil-
ica functionalized with pyridine sites: A versatile heterogeneous catalyst for Heck, Sono-
gashira, and cyanation reactions. Tetrahedron 2007, 63, 9784–6790.
´
´
33. Komaromi, A.; Novak, Z. Effcient copper-free Sonogashira coupling of aryl chlorides
with palladium on charcoal. Chem. Commun. 2008, 4968–4970.
34. Jana, S.; Dutta, B.; Bera, R.; Konar, S. Imobilization of palladium in mesoporous silica
matrix: Preparation, characterization, and its catalytic efficacy in carbon–carbon coupling
reactions. Inorg. Chem. 2008, 47, 5512.
35. Agawa, T.; Miller, S. Reaction of silver acetylide with acylpyridinium salts: N–Benzoyl-2-
phenylethynyl-1,2-dihydropyridine. J. Am. Chem. Soc. 1961, 83, 449.
36. Yanga, F.; Cuia, X.; Lia, Y.; Zhanga, J.; Rena, G.; Wu, Y. Cyclopalladated ferrocenyli-
mines: Efficient catalysts for homocoupling and Sonogashira reaction of terminal alkynes.
Tetrahedron 2007, 63, 1963.