An improved Suzuki–Miyaura cross-coupling reaction with the aid of in situ generated PdNPs: evidence for enhancing effect with biphasic system

Article abstract of DOI:10.1016/j.tetlet.2016.05.098

We present here an improved Suzuki–Miyaura cross-coupling in WERSA (Water Extract of Rice Straw Ash). We found that, although the reaction can be run in neat water, use of alcoholic co-solvent dramatically enhances the yield and generates in situ PdNPs during the reaction. The PdNPs were characterized by TEM and powder XRD analysis. The rice straw ash was characterized by EDX, Flame photometry, and Ion-Exchange chromatography to reveal a broad range of active metal species. The chemical analysis reports of ash showed the presence of oxides of K, Na, and Ca, which probably in the presence of water produces the corresponding hydroxides responsible for the basicity.

Full text of DOI:10.1016/j.tetlet.2016.05.098

Accepted Manuscript
An improved Suzuki-Miyaura cross-coupling reaction with the aid of in-situ
generated PdNPs: Evidence for enhancing effect with biphasic system
Abhijit Mahanta, Manoj Mandal, Ashim Jyoti Thakur, Utpal Bora
PII:
S0040-4039(16)30641-4
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.05.098
TETL 47717
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
7 April 2016
24 May 2016
25 May 2016
Please cite this article as: Mahanta, A., Mandal, M., Thakur, A.J., Bora, U., An improved Suzuki-Miyaura cross-
coupling reaction with the aid of in-situ generated PdNPs: Evidence for enhancing effect with biphasic system,
Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.05.098
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An improved Suzuki-Miyaura cross-coupling reaction with the aid of in-situ
generated PdNPs: Evidence for enhancing effect with biphasic system
Abhijit Mahantaa, Manoj Mandalb, Ashim Jyoti Thakura* and Utpal Boraa*

1
Tetrahedron Letters
An improved Suzuki-Miyaura cross-coupling reaction with the aid of in-situ
generated PdNPs : Evidence for enhancing effect with biphasic system
Abhijit Mahantaa, Manoj Mandalb, Ashim Jyoti Thakura* and Utpal Boraa*
aDepartment of Chemical Sciences, Tezpur University (A central University), Tezpur, Napaam-784028, Assam, India
bDepartment of Chemistry, Dibrugarh University, Dibrugarh-786004, Assam, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
We present here an improved Suzuki-Miyaura cross-coupling in WERSA (Water Extract of Rice
Straw Ash). We found that, although the reaction can be run in neat water, use of alcoholic co-
solvent dramatically enhances the yield and generates in-situ palladium nanoparticles during the
reaction. The palladium nanoparticles were characterized by TEM and powder XRD analysis.
The rice straw ash was characterized by EDX, Flame photometry and Ion-Exchange
chromatography to reveal a broad range of active metal species. The chemical analysis reports of
ash showed the presence of oxides of K, Na and Ca, which probably in presence of water
produces the corresponding hydroxides responsible for the basicity
Available online
Keywords:
Palladium NPs
Suzuki-Miyaura
Co-solvent
2009 Elsevier Ltd. All rights reserved.
Room temperature
Biaryls are privileged motifs in the industrial research as they are
the significant components of numerous drugs, natural products
and advanced functional materials.1-4 In recent years, the
palladium catalyzed Suzuki-Miyaura cross-coupling reaction for
the synthesis of biaryl derivatives has been applied widely due to
its mild reaction condition and wide substrate scope.5-6 In the
catalytic cycle of the Suzuki-Miyaura reaction the most crucial
step is the oxidative addition, and hence, research is focused on
the development of palladium complexes containing electron-rich
ligands, mostly phosphorus- and nitrogen-based, which
accelerates the oxidative addition step by increasing the electron
density over palladium.7-9 Although, these ligands are excellent in
stabilizing palladium species, they are usually costly, toxic,
inseparable, and often hamper the easy isolation and purification
of the products. To overcome this, ligandless catalysis seems
particularly well suited, because of profound advantage of simple
recovery and efficient cost/reactivity relationship.10-11 Moreover,
the Suzuki-Miyaura coupling reaction is highly dependent on the
presence of external base and solvent.12-16 A base during the
transmetalation activates the organoboron species and assists in
the transfer of the organic group bound to electropositive boron
to the organopalladium species. Thus, a proper selection of base
often signifies high efficiency of cross-coupling reaction and
lowers the side-reactions due to incompatible functional groups,
and homo-coupling17-18 and protodeboronation19-20 reactions. A
reaction solvent is often essential during various steps, such as,
reactant mixing, uniform energy supply, proper isolation etc.
Thus, to make a protocol benign and economically sustainable a
catalytic system involving commercially available ligandless
metal catalyst, moderate basicity with wide compatibility is one
of the hot topics in green chemistry.
Recently, Sarma et al have reported a novel Pd(OAc)2-
catalyzed Suzuki-Miyaura coupling reaction at room temperature
using “Water Extract of Rice Straw Ash” (WERSA) as the source
of base.21 Although, water has a strong ability of solvation
especially for polar and ionic substances, the reaction delivers
comparatively lower efficiency in WERSA, possibly due to the
non-polar reactants and products which are not miscible with
water and may gets clustered or forms liquid or solid phase
during the reaction.22 As part of our ongoing efforts to develop
sustainable protocols,23-25 we decided to revisit the coupling
chemistry of WERSA with the aim to maximize the atom
economy and to identify the exact role played by the extract
during the reaction. The corresponding agro-waste rice straw-
derived ash was analyzed by Energy-dispersive X-ray
spectroscopy (EDX), Ion chromatography (IC) and Flame
photometry. Moreover, an attempt was also made to improve the
efficiency of the Suzuki-Miyaura cross-coupling reaction by
employing isopropanol co-solvent. During our investigation, we
have also found that the isopropanol-WERSA enables the
reduction of Pd (II) to Pd(0) and generates palladium
nanoparticles (Pd NPs) even in the absence of the normally
adopted reducing agents. The coupling products were isolated
and characterized using 1H and 13C NMR spectroscopy.
Sarma et al have presented a general method for the
room temperature external base-free Suzuki-Miyaura coupling of
aryl(or hetero aryl) bromides and arylboronic acids in WERSA.
While a wide range of functional groups on the reacting substrate
are tolerated in the reaction, only the coupling with electron rich

2
Tetrahedron
bromoarene worked well with high efficiency. Our first
observation suggested that the biphasic system coated the Pd NPs
objective in reassessing the methodology was to determine the
role played by WERSA during the reaction. Since, metal ions or
oxides can react with water to produce metal hydroxides; the
above distribution data substantiates the basic nature of WERSA.
Our next investigation was to improve the efficiency of
and kept them strongly attached to each other.31
the cross-coupling reaction. We revisited the reaction prototype;
phenylboronic acid (1.2 mmol), 4-bromonitrobenzene (1.0 mmol)
Pd(OAc)2 (1 mol%) and WERSA (3 mL) at room temperature
and found 45% of the isolated yield (Table 1, entry 1). In the next
step, we intended to observe the reaction protocol by organic “co-
solvent” effect. In literature, several reports mentioned the use of
organic-water co-solvents, viz. water-DMF,26 water-THF,27
water-alcohol28-30 etc., which assist in the complete dissolution of
the organic substrates, and enhances the rate of reaction. To our
delight, the reaction proceeded with 87% isolated yield within
3.5 h in ethanol-WERSA (1:1) (Table 1, entry 3). On further
optimizing with different co-solvents, we found that the use of
isopropanol-WERSA (1:1) gives highest efficiency (Table 1,
entry 4). However, lower ratio of WERSA decreases the yield of
the desired product (Table 1, entry 5).
Fig. 1: TEM images of Pd NPs and Pd NPs distributions
XRD analysis was performed to investigate the size and
structure of recovered Pd NPs (Fig. 2). Three peaks were
observed at 2θ=39.55°, 45.94° and 67.64° corresponding to the
reflections of (111), (200), and (220) planes of Pd NPs (JCPDS
no. 88-2335) respectively. The broadening of the peak indicated
Table 1. Optimization of reaction condition for catalyst and
solventa
that the palladium particles were of nano-size.
Entry
Pd(OAc)2
(mol%)
Solvent (4 mL)
Rice straw Time
Yield
(%)b
45
45
87
ash (g)
(h)
12
c1
2
1
1.5
1
WERSA
WERSA
WERSA-EtOH
(1:1)
-
-
-
12
3
3.5
4
5
1
1
WERSA-
iPrOH (1:1)
WERSA-
iPrOH (1:3)
WERSA-DMF
(1:1)
WERSA-
iPrOH (1:1)
H2O-iPrOH
(1:1)
H2O -iPrOH
(1:1)
H2O -iPrOH
(1:1)
H2O -iPrOH
(1:1)
-
-
3.5
6
89
80
87
75
89
89
89
82
6
1
-
3
7
0.5
1
-
4
8
0.5
0.7
0.3
0.2
3.5
3.5
3.5
6
9
1
10
11
1
Fig. 2. X-ray diffraction pattern of PdNPs
1
aReaction condition: 4-bromonitrobenzene (1 mmol),
Phenylboronic acid (1.2 mmol), Solvent (4 mL), ca. 27 °C in
air, unless otherwise noted. isolated yield, 2mL of WERSA
Recently, we have reported that the in-situ generated catalytic
system based on palladium salt with sodium sulphate, sodium
acetate or sodium chloride exhibited excellent catalytic activity in
the Suzuki-Miyaura cross-coupling reaction at room temperature
in water and isopropanol.23 Later on these catalytic systems have
received a wide range of applications in various organic
syntheses.27,32-34 Moreover, the XPS and FT-IR data provides
strong evidence for the existence of interactions between the salt
particles with palladium catalyst and aryl bromide.35 It is believed
that such synergic interactions are perhaps possible under present
reaction condition with WERSA. Being successful in our first
aim to improve the yield of the desired cross-coupled product, in
the next assessment, we tried to generate an in-situ alkaline
system in the reaction medium. From analysis it was clear that
the rice straw ash contained metals like K, Na, Li, Ca, Mg etc.
So, we believed that the contained metal would have the
capability to form metal hydroxide with water in the reaction
b
c
was used.
Given the remarkable improvement demonstrated by the
WERSA-iPrOH, we became interested in investigating the role
of the co-solvent during the reaction. Transmission electron
microscopy (TEM) of the reaction mixture after the completion
indicated the formation of homogeneous palladium nanoparticles
Pd NPs with spherical aggregate structures having smaller and
average particle size of 5-10 nm (Fig. 1). The production of
PdNPs, in the absence of the normally adopted reducing agents,
is most likely due to the isopropanol which enables the reduction
of Pd(II) to Pd(0), while its hydroxyl groups are oxidized to
carbonyl groups. The TEM image showed the aggregates of Pd
NPs dispersed over the thin layer of WERSA-isopropanol. This

3
from their corresponding metals and these would be suitable
bases for the concerned reaction. Based upon this point of view,
the reaction of phenyl boronic acid (1.2 mmol) and 4-bromo
nitrobenzene (1 mmol) was performed under isopropanol: water
(1:1) with 0.5 g of rice straw ash keeping the amount of catalyst
same with the earlier reaction of isopropanol: WERSA (1:1)
(table 1, entry 8) and more interestingly 89% of isolated yield of
the desired cross-coupled product was realised. Several test
reactions were carried out using different amounts of ash to find the
optimum amount of ash required for the reaction.On increasing the
ash loading from 0.5 g to 0.7 g no considerable effect on the
reaction efficiency was noticed (Table 1, entry 9). Thus, varying
the amount of ash keeping other conditions constant we found
that 0.3 g of the ash was enough for the suitable conversion to the
desired product (table 1, entry 10). With the optimum reaction
conditions, we next investigated the substrate scope and
limitations of the reaction by using diverse range of aryl
bromides and arylboronic acids (Table 2). Both electron
withdrawing and electron donating aryl bromides underwent
effective coupling reactions with arylboronic acid to afford the
desired biaryls in excellent yields (89-96%) in water-isoproponol.
Moreover, the catalytic system is equally effective for differently
substituted arylboronic acids (Table 2).36 These results are quite
significant as the desired biaryls could be achieved at room
temperature using water-isoproponol co-solvent and with natural
base and low catalyst loading without using any ligand.
Fig. 3. Preparation of the WERSA and our development
Analysis of Rice straw ash:
The alkaline nature of the extract was determined
through litmus test, and its pH was found to be around 12. The
distribution of elements as based on the EDX analysis of the rice
straw ash is shown in Fig. 4. The report reveals a very high
concentration of oxides of potassium followed by calcium and
magnesium.
Table 2: Rice straw ash promoted Suzuki-Miyaura cross-
coupling reaction of aryl bromides and arylboronic acidsa
Entry
R1
R2
Time (h)
Yield
(%)b
89
93
96
93
95
94
96
95
94
92
89
92
95
90
94
91
84
46
85
85
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
-H
4-Me
4-CHO
-H
4-OMe
4-OMe
4-tert-butyl
4-CN
4-F
2-Me
4-Cl
4-F
-H
4-NO2
4-OMe
-H
4-COMe
-H
4-OMe
4-NO2
-H
3.5
1
1
2.5
1.5
1
1
1.5
4
1
1.5
1
1
3
2
2
3.5
24
2.5
4
-H
Fig. 4. EDX spectrum of rice straw ash.
4-OMe
4-NO2
4-OMe
-H
-H
-H
-H
3-Me
2-Me
3-OMe
2-CHO
3-NH2
4-OMe
4-OMe
Thereafter, we have performed the Ion Chromatography and
Flame photometry to analyse the ion and metal concentration of
the water-extract. The results are summarized Fig. 5. and Table
3.
4-Me
3-Me
HO
B
HO
N
F
Br
N
aReaction condition: Arylboronic acid (1.2 mmol), aryl
bromide (1 mmol), Pd(OAc)2 (1 mol%), i-PrOH (2 mL), Water
(2 mL), ca. 27 °C in air, unless otherwise noted. bisolated yield.
Experimental
Procedure for preparation of WERSA
The WERSA was prepared by burning oven dried rice
straw to ashes. Thereafter, 10 g of the ash was suspended in
distilled water (100 mL) and stirred for half an hour at room
temperature. The mixture was then filtered and the filtrate is
known as WERSA (Fig. 3).

4
Tetrahedron
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Am. Chem. Soc. 2006,128, 6829-6836.
Peak
Number
Retention
time
(min)
Area
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(S/cm) S/cm
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3
4
5
5.522
7.230
11.085
23.077
25.575
0.0043
0.7164
39.5759 83.839
0.0746
0.0031
0.030
3.353
0.054
28.315
3215.575
3.438
Lithium
Sodium
Potassium
Calcium
Magnesium
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0.024
0.075
Fig. 5. Metal concentration of the natural base by Ion-Exchange
chromatography.
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Carbohydr. Polym. 2015, 116, 51-59.
Table.3. Comparisons of metals contents (in ppm) in
WERSA using Ion-Exchange chromatography and Flame
photometry analysis.
Entry
Metal
Metal
concentration
by IC [ppm]
Trace
Metal concentration
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1060.
by flame photometry [ppm]
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1
2
3
4
5
Li
Na
K
Trace
25.36
3025.25
4.05
28.31
3215.5
3.43
Trace
Ca
Mg
Trace
In conclusion, we have developed an improved protocol for
Suzuki-Miyaura reaction with the aid of in situ generated PdNPs
in biphasic media. The reaction has been performed with rice
straw ash in water-isopropanol without using any organic or
inorganic base. The metal oxide present in rice straw ash is
responsible for the basicity of the aqueous reaction medium. The
main advantage of the present reaction system is the use of an
abundant agro waste, rice straw ash as alternative base in Suzuki-
Miyaura reaction.
34. Xu, S.; Chen, H.-H.; Dai, J.-J.; Xu, H.-J. Org. Lett. 2014, 16,
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Zhang, P.; Han, B . Green Chem. 2014, 16, 1198-1201.
36. A 50 mL round-bottom flask was charged with a mixture of aryl
boronic acid (1.2 mmol), aryl halide (1 mmol), 2 mL distilled
water and 2 mL of iso-propanol. To this mixture 1 mol% of
Pd(OAc)2 was added followed by the addition of the 0.3 g of rice
straw ash. The whole reaction mixture was stirred for the required
time resulting a black colour solution. The reaction was monitored
by TLC and after completion of the reaction the solution was
extracted three times with ethyl acetate (3x10 mL). The products
were purified by column chromatography and confirmed by 1H
and 13C NMR spectroscopy.
Acknowledgement
Authors are thankful to Tezpur University for providing
infrastructure facility to carry out the project and also for
providing start up grant to UB and institutional fellowship to A.
M.
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5
Research highlights:
 Improved Suzuki-Miyaura reaction with in situ PdNPs in biphasic media is developed.
 The reaction is performed without using any conventional organic or inorganic base.
 The rice straw ash in aqueous media is acting as base in this reaction.
 An abundant agro waste is used as alternative base in Suzuki-Miyaura reaction.
 Chemical investigation of rice straw is shown the presence K, Na, Li, Ca, Mg metal