Palladium nanoparticles catalyzed Suzuki cross-coupling reactions in ambient conditions

Article abstract of DOI:10.1016/j.catcom.2012.10.020

An efficient pathway to synthesize biaryls and terphenyls through ligand-free palladium nanoparticles (PdNPs) catalyzed Suzuki cross-coupling reactions has been developed. Mild reaction conditions, high yields of desired products, absence of inert atmosphere and short reaction times are the notable features of this method.

Full text of DOI:10.1016/j.catcom.2012.10.020

Palladium nanoparticles catalyzed Suzuki cross coupling reactions in ambient
conditions
Pavan Kumar Mandali, Dillip Kumar Chand
PII:
DOI:
Reference:
S1566-7367(12)00406-2
doi: 10.1016/j.catcom.2012.10.020
CATCOM 3317
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Catalysis Communications
Received date:
Accepted date:
27 August 2012
23 October 2012
Please cite this article as: Pavan Kumar Mandali, Dillip Kumar Chand, Palladium
nanoparticles catalyzed Suzuki cross coupling reactions in ambient conditions, Cataly-
sis Communications (2012), doi: 10.1016/j.catcom.2012.10.020
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Palladium nanoparticles catalyzed Suzuki cross coupling reactions in
ambient conditions
*
Pavan Kumar Mandali, Dillip Kumar Chand
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600 036, India
[
Fax: (+91) 44 2257 4202; Tel: (+91) 44 2257 4224; E-mail: dillip@iitm.ac.in]
Abstract
An efficient pathway to synthesize biaryls and terphenyls through ligand-free palladium
nanoparticles (PdNPs) catalyzed Suzuki cross coupling reactions has been developed. Mild
reaction conditions, high yields of desired products, absence of inert atmosphere and short
reaction times are the worth noting features of this method.
Keywords: Suzuki cross-coupling, Palladium nanoparticles, Ambient conditions, Terphenyl
derivatives, Heterocyclic ligands.
1
. Introduction
Palladium nanoparticles (PdNPs) supported by a variety of conventional and non-
conventional supports have been promising catalysts for Suzuki cross coupling reactions [1-
3
]. Dendrimers, polymers, anthracene derivatives and metal-organic frameworks stabilized
colloidal palladium nanoparticles (PdNPs) are well exploited as catalysts for the Suzuki
coupling reactions [4-10]. El-Sayed and co-workers [11] found that palladium nanoparticles
stabilized by hydroxyl-terminated poly(amidoamine) (PAMAM) dendrimers (G3-OH, G
represents the generation) could efficiently catalyze the Suzuki-Miyaura reactions. Astruc’s
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group [12] have investigated the catalytic activity of palladium dodecanethiolate
nanoparticles towards Suzuki coupling reactions which required prolonged reaction time.
Recently, Das and co-workers [13] reported Suzuki coupling by using DMF as the solvent at
high temperature. Cao and co-workers [14, 15] successfully tested the catalytic activities of
cucurbit[n]uril (n= 6,7,8) protected PdNPs towards Suzuki cross coupling reactions and the
same group [16] also tested the SBA-15 stabilized PdNPs, Pd/Au alloy NPs towards Suzuki
cross coupling by microwave heating, but C-Br bond was activated at elevated temperatures
and synthesis of terphenyls was not discussed. There are some recent methods in the
literature for coupling reactions by ligand-free PdNPs as catalyst [17, 18]. However, some of
these earlier reports suffer due to the use of bulky, expensive and commercially unavailable
ligands, high boiling solvents and prolonged reaction times. There is a high demand for
simple, inexpensive and easily accessible catalysts for these coupling reactions. Herein, we
report a method for the synthesis of biaryls using ligand-free Suzuki cross coupling reactions
catalyzed by palladium nanoparticles at ambient conditions. Terphenyls are also successfully
synthesized by the same method. Importantly, the terphenyls was precipitated out from the
reaction mixture there by, making this method attractive compared to existing methods.
2
. Experimental
2
.1. General
All the chemicals were purchased from Sigma-Aldrich chemical company. The PdNPs were
characterized by recording powder XRD pattern, TEM, HRTEM and FEG-SEM micrographs
and X-ray photoelectron spectroscopy (see SI). The coupling reactions were monitored by
1
13
TLC (silica gel). H and C NMR of the products were recorded at room temperature with a
Bruker Avance-400 and 500 FT NMR spectrometers. CDCl was used as solvent and TMS
3
as the internal standard. HPLC data was obtained by using Waters HPLC instrument fitted
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with a 515 pump and 2487 dual- wavelength absorbance detector. The TEM sample was
prepared by taking drop of metal nanoparticle solution on the carbon coated 200 mesh copper
grid and allowed to dry in air at room temperature. Samples for SEM, XRD and XPS were
prepared by isolating PdNPs in solid state by evaporating the solution in rotavapor.
2
.2. Preparation of palladium nanoparticles (PdNPs)
A 2mM solution of Pd(II) was prepared by dissolving palladium (II) acetate (0.0045 g) in a
:1 MeCN/MeOH mixture (10 mL). The yellow solution was stirred at room temperature for
1
about 3 h where upon a brownish-black colour was developed due to reduction of Pd(II) to
Pd(0) [19].
2
.3. Typical procedure for the synthesis of biaryls by PdNPs catalyzed Suzuki coupling
reactions:
To a freshly prepared solution of PdNPs (10 mL, 0.02 mmol), K CO (0.276 g, 2 mmol) was
2
3
added followed by arylhalide (1 mmol) and arylboronic acid (1.5 mmol). Then, the reaction
was allowed to stir at room temperature in open atmosphere. The reaction was monitored by
TLC and was stopped after the complete consumption of starting material. Then the mixture
was centrifuged and filtered. The filtrate was evaporated to get unclean products and hence
purified by column chromatography using hexane as the eluent. Characterization of products
1
13
was done by H, C NMR and ESI-MS (see SI).
.4. Typical procedure for synthesis of terphenyls:
To a freshly prepared solution of PdNPs (10 mL, 0.02 mmol), required amount of K CO (2
2
2
3
mmol) was added followed by aryldihalides/ arylhalide (1mmol) and arylboronic acid
3mmol)/ diboronic acid (0.75mmol). Then, the reaction was allowed to stir at room
(
temperature in open atmosphere. The reaction was monitored by TLC and was stopped after
the complete consumption of starting material. The desired product got precipitated out
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which was separated by filtration and extracted with chloroform. The chloroform layer was
evaporated to get the terphenyl in pure state.
2
.5. Recyclability of the catalyst:
Recyclability of a catalyst plays an important role in the view of commercial applications.
We investigated the recyclability of the catalytic system by choosing the coupling of
phenylboronic acid with p-bromotoluene as model reactions. After one run, the reaction
mixture was filtered off. The residue was washed with hexane and then with methanol for
two times to extract the organic products, dried under reduced pressure and was re-dispersed
in 10 mL of solvent mixture (CH OH: CH CN) for the next catalytic cycle. The catalyst
3
3
system was found to be reusable without any significant loss of the catalytic activity, for at
least six cycles that we followed (see Fig 1).
2
.6. Hot filtration test:
The presence of colloidal Pd species in the solution was examined by hot filtration test for the
coupling reaction of p-bromoacetophenone and phenylboronic acid. After ~25% completion
0
of the coupling reaction, the solution was heated to 60 C and filtered off with a 0.2 µm pore
size filter under hot condition and then the filtrate was allowed to stir at room temperature
with further addition of K CO (2 mmol). Progress of the reaction was monitored by HPLC,
2
3
at an interval of successive 20 min, using CH CN: H O (60:40) as a mobile phase and C18 as
3
2
a reverse phase column (Fig 2). The HPLC data showed that the 90% completion of coupling
reaction even after the catalyst was filtered out. Thus the filtrate presumably contains
catalytically active palladium species.
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3
. Results and discussion
In this communication, we disclose our work on the ligand free PdNPs catalyzed Suzuki
coupling reactions at ambient conditions. Initially, a model Suzuki coupling reaction was
performed by reacting p-bromoacetophenone with phenylboronic acid. The reaction was
carried out successfully at room temperature under open air without any special precautions.
The results indicated that cross coupling completed within 2 h in the presence of 2 mol% of
PdNPs.
The methodology developed was effectively applied to a wide range of aryl iodides and
bromides. All these coupling reactions were carried out at room temperature at ambient
conditions which resulted in good to excellent isolated yields of the products within short
reaction times. The results presented in Table 1, summarize Suzuki cross coupling of
phenylboronic acid and aryl halides containing a variety of substituents. The effect of steric
hindrance has been studied by coupling ortho-methylphenylboronic acid with ortho or para
substituted aryl bromides (Table 1, entries 15- 18). Thus, the steric crowding around the
reaction sites is acceptable as it could not hinder the synthesis. However, our attempts to
activate C-Cl bond for coupling reactions was found to be unsuccessful. The ICP-AES
analysis revealed that there was no palladium content in the isolated biaryl derivatives.
We have also investigated the reactivity of the bromo-substituted heteroaromatics like,
pyridine and pyrimide derivatives with phenylboronic acid (Table 2). The reactions
proceeded smoothly with nearly quantitative yields.
The substantial catalytic activity of PdNPs was observed up to six cycles without significant
loss of activity. Also, the hot filtration test indicated presence of catalytically active colloidal
Pd species in the solution.
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Scanning electron microscopy (SEM) used to study the surface of the catalyst. The SEM
image concluded that the diameters of PdNPs are in the range of nanometers (see SI). TEM
measurements revealed that size of the palladium nanoparticles ranges from ~ 4- 6nm and
HRTEM picture of PdNPs shows the highly crystalline nature of the sample (see SI). Powder
XRD pattern of the catalyst before the catalysis and after six catalytic cycles (see SI) are
found to be identical and displayed the usual fcc lattice as expected for palladium. The XPS
spectrum of PdNPs shows two well resolved peaks at 335.6 and 340.8 eV corresponding to
Pd3d5/2 and Pd3d3/2 respectively, refer to C = 285 eV, indicating the zerovalent Pd (see SI).
1s
The peaks at 337.4 and 342.7 eV correspond to PdO [20]. It was confirmed that 68.6% of the
total Pd present in zero oxidation state and rest as a PdO by taking their relative peak areas.
Thus the formation of some PdO could not be avoided, also found by other workers [21].
Terphenyls and its derivatives play promising roles in the fields of high performance
engineering and optical materials, liquid crystals, as well as spacers particularly in catenanes
and porphyrins chemistry [22, 23]. Moreover, terphenyls are found useful in a wide range of
biological applications including neuroprotective, antithrombotic, anticoagulant and cytotoxic
activities [24]. The reported methods for the preparation of terphenyls recommend the
reaction of aryl zinc reagents with functionalized biphenyl nonaflates, Grignard reagents with
dihalobenzenes and triazene-substituted arylboronic esters [25-27]. As of late, Suzuki cross
coupling reactions are also employed for the synthesis of biaryls, terphenyls and polyaryls by
using a variety of palladium sources [28-30]. Although, there are some recent reports which
narrate the synthesis of biaryls using palladium nanoparticles (PdNPs), the synthesis of
terphenyls is not well exploited by using these palladium nanoparticles [31-33]. In fact, most
of the above quoted methods employ commercially unavailable materials and harsh reaction
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conditions. In this work, we report a simple and most convenient reaction pathway, in terms
of synthesis as well as easy isolation of the products.
We focused our attention to synthesize terphenyls by two different ways as shown in schemes
1
and 2. The best of this methodology is the easy separation of the products. The products
were precipitated out during the reaction which enabled us to separate them easily by
filtration and purify by extracting with chloroform. A variety of terphenyls were synthesized,
by coupling aryl di-halides with phenyl mono-boronic acids (Scheme 1, Tables 3 and 4) and
aryl mono-halides with phenyl di-boronic acids (Scheme 2, Tables 5 and 6). The dibromo,
diiodo and iodo-bromo derivatives (Table 3, entries 1-3), provided comparable reactivity
when coupled with phenylboronic acid. Sterically hindered substrates (Table 3, entries 4-6)
also afforded their corresponding terphenyls with high yields. Synthesis of ortho and meta-
terphenyls is summarized in Table 4. Here also the products were isolated in good yields
irrespective of position and nature of the halides (iodo or bromo) substitution.
Suzuki cross-coupling reactions between aryl bromides and aryl diboronic acids to synthesize
terphenyls was first reported by Abell et al. [34] by using Pd(PPh ) as a catalyst under inert
3
4
atmosphere. Later, Chaumeil and co-workers [35] reported synthesis of symmetric terphenyls
under reflux conditions and inert atmosphere by employing Pd(PPh ) as a catalyst.
3
4
Afterward, the use of aryl diboronic acids for the synthesis of terphenyls was not well
explored. We have prepared a variety of p-terphenyls by coupling aryl mono-halides with
phenyl di-boronic acids (Scheme 2, Tables 5 and 6). In our work, we have screened a wide
range of functionalized aryl halides which contain functional groups such as NO , COCH ,
2
3
OCH , CHO and CN for the preparation of terphenyls in good yields. Among these reactants,
3
4
-chloro-1-iodobenzene is more interesting (Table 5, entry 8) because the resultant product
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contains untouched chlorides thus offering chances for further derivatization. The ICP-AES
analysis revealed that there was no palladium content in the isolated terphenyl derivatives.
Pyridine appended bidentate non-chelating ligands are useful in supramolecular coordination
chemistry. We offer a simple method for the synthesis of such compounds as discussed
below. The reaction of bromo susbstituted pyridine, pyrimidine and quinoline derivatives
with diboronic acids were carried out to prepare corresponding ligands in reasonable yields.
The data is summarized in Table 6. For entries 3 and 4, products were precipitated during the
reaction whereas products of entries 1 and 2 were purified by column chromatography.
4
. Conclusion
In conclusion, we have successfully screened the catalytic activity of our PdNPs towards C-C
bond formation via Suzuki cross coupling reactions at ambient conditions. A wide variety of
aryl iodides and bromides were coupled with different boronic acids within short reaction
times. Synthesis of ortho-, meta- and para-terphenyls is demonstrated with a convenient
isolation process due to precipitation of the products. A family of ligands required for
supramolecular coordination chemistry can be prepared by this method. Since the reactions
can be carried out in a very simple manner at room temperature without inert atmosphere this
method is likely to find applications in synthesis.
Acknowledgments: D.K.C. thanks CSIR, India for financial support. M. P. K thanks IIT
Madras for the fellowship.
References
[
[
1] R. Narayanan, Molecules. 15 (2010) 2124-2138.
2] A. Fihri, M. Bouhrara, B. Nekoueishahraki, J.M. Basset, Chem. Soc. Rev. 40 (2011)
5
181-5203.
8

ACCEPTED MANUSCRIPT
[
[
[
[
[
3] I. Favier, D. Madec, E. Teuma, M. Gomez, Curr. Org. Chem. 15 (2011) 3127-3174
4] A. Roucoux, J. Schulz, H. Patin, Chem. Rev. 102 (2002) 3757-3778.
5] R. Narayanan, M. A. El-Sayed, J. Am. Chem. Soc.125 (2003) 8340-8347.
6] D. Astruc, C.Ornalas, A.K. Diallo, J. Ruiz, Molecules. 15 (2010) 4947-4960.
7] Y. Huang, Z. Zheng, T. Liu, J. Lü, Z. Lin, H. Li, R. Cao, Catal. Commun. 14 (2011)
2
7-31.
[
8] D. Sanhes, E. Raluy, S. Retory, N. Saffon, E. Teuma, M. Gomez, Dalton. Trans. 39
2010) 9719-9726.
(
[
[
9] Y. Huang, Z. Lin, R. Cao, Chem. Eur. J. 17 (2011) 12706-12712.
10] Y. Huang, S. Gao, T. Liu, J. Lu, X. Lin, H. Li, R. Cao, Chem. Plus. Chem. 77 (2012)
1
06-112.
[
[
[
[
[
[
[
11] Y. Li, M.A. El-Sayed, J. Phys. Chem. B. 105 (2001) 8938-8943.
12] F. Lu, J. Ruiz, D. Astruc, Tetrahedron Lett. 45 (2004) 9443-9445.
13] P. Das, D. Sharma, A.K. Shil, A. Kumari, Tetrahedron Lett. 52 (2011) 1176-1178.
14] M. Cao, J. Lin, H. Yang, R. Cao, Chem. Commun. 46 (2010) 5088-5090.
15] M. Cao, Y. Wei, S. Gao, R. Cao, Catal. Sci. Technol. 2 (2012) 156-163.
16] Z. Zheng, H. Li, T. Li, R. Cao, J. Catal. 270 (2010) 268-274.
17] J. Durand, E. Teuma, F. Malbose, Y. Kihu, M. Gomez, Catal. Commun. 9 (2008) 273-
2
75.
9

ACCEPTED MANUSCRIPT
[
[
[
18] H. Li, L. Wang, M. Yang, Y. Qi, Catal. Commun. 17 (2012) 179-183.
19] J. Athilakshmi, S. Ramanathan, D. K. Chand, Tetrahedron Lett. 49 (2008) 5286-5288.
20] C. D. Wagner, W. M. Riggs, L. E. Davis, J. F. Moulder, Hand-book of X-ray
Photoelectron spectroscopy, Perkin-Elmer, Physical Electronics Divison, Eden Prairie
1
979.
[
21] B. Genorio, T. He, A. Meden, S. Polanc, J. Jamnik, J. M. Tour, Langmuir. 24 (2008)
1523-11532.
1
[
[
[
[
[
22] P.Bordat, R. Brown, Chem. Phys. Lett. 331 (2000) 439-445.
23] W.M.F. Fabian, J.M.Kauffman, J. Lumin. 85 (1999) 137-148.
24] J-K. Liu, Chem. Rev. 106 (2006) 2209-2223.
25] M. Rottlander, P. Knochel, J. Org. Chem. 63 (1998) 203-208.
26] S. Li, B. Wei, P. M. N. Low, T.S.A. Hor, F. Xue, T. C. W. Mak, J. Chem. Soc. Dalton
Trans. (1997) 1289-1293.
[
[
[
[
27] C. Y. Liu, A. Gavryushin, P. Knochel, Chem. Asian. J. 2 (2007) 1020-1030.
28] D. J. Sinclair, M. S. Sherburn, J. Org. Chem. 70 (2005) 3730-3733.
29] L. Liu, Y. Zhang, B. Xin, J. Org. Chem. 71 (2006) 3994-3997.
30] J. M. A. Miguez, L. A. Adrio, A. Sousa-Pedrweres, J. M. Vila, K. K. Hii, J. Org. Chem.
7
2 (2007) 7771-7774.
[
31] M. V. Escarcega-Bobadilla, E. Teuma, A. M. Masdeu-Bulto, M. Gomez, Tetrahedron.
7 (2011) 421-428.
6
1
0

ACCEPTED MANUSCRIPT
[
[
32] Z. Du, W. Zhou, F. Wang, J.-X. Wang, Tetrahedron. 67 (2011) 4914-4918.
33] K. L. Dos Santos Castro, P. G. de Lima, L. S. M. e Miranda, R. O. M. A. de Souza,
Tetrahedron Lett. 52 (2011) 4168-4171.
[
[
34] M. H. Todd, S. Balasubramanian, C. Abell, Tetrahedron Lett. 38 (1997) 6781-6784.
35] H. Chaumeil, C. Le Drian, A. Defoin, Synthesis. 6 (2002) 757-760.
1
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The Sequence of Schemes and Tables:
Table 1. Suzuki cross coupling reactions of aryl halides and aryl boronic acids.
Table 2. Suzuki cross coupling reactions of hetero-arenes and phenyl boronic acid.
Scheme 1. Suzuki cross coupling reactions between aryl dihalides and aryl monoboronic
acids.
Scheme 2. Suzuki cross coupling reactions between aryl monohalides and aryl diboronic
acids.
Table 3. Synthesis of p-terphenyls using phenyl boronic acid
Table 4. Synthesis of o-terphenyls and m-terphenyls
Table 5. Suzuki cross coupling reactions between aryl monohalides and phenyl diboronic
acid.
Table 6. Suzuki cross coupling reactions of hetero-arenes and phenyl diboronic acids.
Figure 1. Data showing recyclability of catalyst
Figure 2. A plot showing percentage of product versus time during Suzuki coupling reaction
of 4-bromoacetophenone and phenylboronic acid: (a) Standard run and (b) Run during hot
filtration
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4

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Figure 1. Data showing recyclability of catalyst
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Figure 2. A plot showing percentage of product versus time during Suzuki coupling
reaction of 4-bromoacetophenone and phenylboronic acid: (a) Standard run and (b)
Run during hot filtration
2
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Graphical abstract
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Highlights
A variety of biaryls and terphenyls are syntheized efficiently by ligand-free palladium
nanoparticles (PdNPs) catalysed Suzuki coupling reactions in ambient conditions.
Terphenyls are isolated from the reaction mixture as precipitates which can be simply
washed to get the pure products.
Simple method to synthesize hetero-atom bearing terphenyls through Suzuki cross
coupling.
2
3