Water mediated Heck and Ullmann couplings by supported palladium nanoparticles: Importance of surface polarity of the carbon spheres

Article abstract of DOI:10.1039/c2gc16430b

Heterogeneous palladium nanoparticle catalysts that are supported on amphiphilic carbon spheres (Pd@CSP) have been utilized for water-mediated Heck coupling reactions of aryl halides with different alkenes under phosphine free as well as aerobic conditions. Furthermore, a variety of Heck coupling reactions using different bases and solvents, including organic polar and non-polar solvents, have been explored. Aryl bromides are also well activated in Heck coupling reactions in organic polar solvent and as well as in water. In addition, Ullmann coupling reactions of aryl iodides have been catalyzed in water with the aid of phase transfer catalysts (PTC) in moderate yields. A plausible mechanism for the catalytic activity of Pd@CSP in the case of the Ullmann reaction is also established. It has been demonstrated that the hydrophobic effects of the catalyst surface play an important role in catalyst activity in water. In addition, the E-factor analysis verified that our present protocol is significantly comparable with other catalytic systems and explains the improved greenness. Moreover, the catalyst described in this process is not only greener, but also retains its significant activity for up to four catalytic cycles for the Heck coupling reactions. The surface polarity of the amphiphilic carbon spheres results in higher activity under these conditions.

Full text of DOI:10.1039/c2gc16430b

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PAPER
Water mediated Heck and Ullmann couplings by supported palladium
nanoparticles: importance of surface polarity of the carbon spheres†
Ahmed Kamal,*a Vunnam Srinivasulu,a B. N. Seshadri,a Nagula Markandeya,a A. Alarifib and
Nagula Shankaraiahc
Received 9th November 2011, Accepted 24th May 2012
DOI: 10.1039/c2gc16430b
Heterogeneous palladium nanoparticle catalysts that are supported on amphiphilic carbon spheres
(Pd@CSP) have been utilized for water-mediated Heck coupling reactions of aryl halides with different
alkenes under phosphine free as well as aerobic conditions. Furthermore, a variety of Heck coupling
reactions using different bases and solvents, including organic polar and non-polar solvents, have been
explored. Aryl bromides are also well activated in Heck coupling reactions in organic polar solvent and as
well as in water. In addition, Ullmann coupling reactions of aryl iodides have been catalyzed in water
with the aid of phase transfer catalysts (PTC) in moderate yields. A plausible mechanism for the catalytic
activity of Pd@CSP in the case of the Ullmann reaction is also established. It has been demonstrated that
the hydrophobic effects of the catalyst surface play an important role in catalyst activity in water. In
addition, the E-factor analysis verified that our present protocol is significantly comparable with other
catalytic systems and explains the improved greenness. Moreover, the catalyst described in this process is
not only greener, but also retains its significant activity for up to four catalytic cycles for the Heck
coupling reactions. The surface polarity of the amphiphilic carbon spheres results in higher activity under
these conditions.
carefully selected traditional organic solvents in terms of the
Introduction
energy to manufacture, cumulative energy demand, and impact
on health and the environment.25 Indeed, the concepts of
The Heck reaction was one of the first direct C–C coupling reac-
tions to have a remarkably wide scope with the use of a palla-
dium (Pd) catalyst, and is of particular interest in terms of
sustainable chemistry.1–7 This powerful reaction is widely used
in industrial and academic applications, mainly for the coupling
of aryl halides to electron-withdrawing terminal olefins.6,8–19
Besides, the iodobenzene (Ar-I) homocoupling reaction
(Ullmann reaction) has been extensively used for the synthesis
of aromatic compounds for fine chemical, agrochemical, and
pharmaceutical applications.20,21 In the context of green chem-
istry, heterogeneous catalysis of the Ullmann reaction carried out
in aqueous conditions is considered environmentally friendly
since water could be considered as the safest solvent.22–24 The
use of water as the reaction media for the organic reactions is
considerably greener compared to CO2, ionic liquids and
environmental factor (E-factor) and atom economy have gradu-
ally become included into conventional organic synthesis in both
industry and academia. Solvents are the main reason for an
insufficient E-factor, especially in fine chemicals and pharma-
ceutical industries.26
In view of the adverse environmental effects associated with
phosphines, it is desirable to develop phosphine-free reactions
under greener conditions for Pd-catalyzed reactions.27–31
Besides, organic synthesis in water has drawn much attention as
it is a non-toxic green solvent.32–38 The use of water as a solvent
particularly in the Heck reaction is important for E-factor
reduction and for the development of safer industrial processes.
One approach is to utilize water dispersible (hydrophilic) Pd
catalysts.7,39 Despite, the synthetic elegance and high turnover
numbers, the non-reusability of the precious metal and the con-
tamination of Pd in isolated products preclude wide synthetic
applications in the pharmaceutical industry.
However, the coupling reactions of Heck substrates proceed
sluggishly in pure water as the organic reagents are not comple-
tely dissolved in water.40 Therefore, besides the usual problems
associated with homogeneous catalysis (catalyst separation,
product contamination, etc.), the conversion of the hydrophobic
substrates is still a critical predicament for water dispersible
catalysts. In order to circumvent these problems, a number of
polymeric materials,41–49 silica,50 carbon,51 silica carbon
aDivision of Organic Chemistry, Indian Institute of Chemical
Technology, Hyderabad 500 607, India.
E-mail: ahmedkamal@iict.res.in; Fax: +91-40-27193189;
Tel: +91-40-27193157
bCatalytic Chemistry Chair, Chemistry Department, College of Science,
King Saud University, Riyadh, Saudi Arabia
cDepartment of Medicinal Chemistry, National Institute of
Pharmaceutical Education and Research (NIPER), Hyderabad-500 037,
India
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2gc16430b
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Fig. 1 TEM images of the Pd@CSP catalyst prior to the reaction (a) and after completion of the reaction (2nd cycle) (b).
composite,52 have been developed and utilized as supports to
perform the Heck coupling reactions in water. Besides, the
“Breslow effect” has demonstrated that organic molecules repel
water molecules and are forced to form clusters in order to
decrease the surface area of the non-polar surface exposed to
water. The hydrophobic aggregates arising from organic mo-
lecules in water will reduce the activation energies and increase
the rate of the reaction significantly. In this context, we presumed
that the water medium brings the organic molecules into close
proximity of the carbon sphere (CSP) support by hydrophobic–
hydrophobic interactions, which may influence the contact
times of substrates with CSP support in the presence of phase
transfer catalysts (PTC).53 Hence, the amphiphilic property of
the Pd@CSP may overcome the mass transfer limitation by
increasing the availability of organic molecules near the CSP
surface.
Various heterogeneous or supported Pd catalysts like Pd on
carbon and a variety of metal oxides are shown to be highly
active for Suzuki-coupling reactions in neat water under mild
reaction conditions.54 It is demonstrated that the surface polarity
of the support plays an important role for the catalyst activity in
water. Pd on amphiphilic carbon as a typical support represents a
simple and green catalyst for the Suzuki–Miyaura reaction.55
However, one of the substrates in the Suzuki reaction i.e., phenyl
boronic acid is easily soluble in water. Besides, both substrates
in the Heck reaction are poorly soluble in water. It is worth men-
tioning that styrene and acrylates are also useful reactants in
water, while they are poorly soluble in this solvent, similar to the
aryl iodide counterpart. In order to extend the concept towards
C–C coupling reactions catalyzed by Pd on an amphiphilic CSP
catalyst in water, we have performed Heck and Ullmann coup-
ling reactions in water under relatively mild reaction conditions
(air, 90 °C, 0.5 mol% of Pd). Moreover, the catalytic activity
was investigated by varying several parameters, such as solvent,
base, and temperature. Among the solvents used, water is the
best solvent system in comparison to other organic solvent
systems in terms of catalyst activity, selectivity and stability. In
addition, we have developed green reaction conditions i.e.,
smaller E-factor (4.05), minimal usage of organic solvent, and a
simple work up procedure. In addition, the greenness of the pro-
tocol is also improved by employing the applications of green
chemistry metrics (E-factor). Furthermore, the comparison of E
factor with several other catalyst systems explained the improved
greenness of the present protocol.
However, the addition of tetrabutylammonium bromide
(TBAB) to stabilize the dissolved Pd catalytic species and to
diffuse the molecules onto the hydrophobic surface of the sphere
in water was necessary for the conversion of various substrates
to the corresponding products. The catalyst showed improved
functional group tolerance to afford good-to-excellent yields of
the products with different aryl halides. The majority of aryl
halides afford good-to-excellent yields with higher amounts of
E-diastereomers in pure water as well as in DMF. The recyclabil-
ity of the CSP-supported Pd nanoparticles (Pd NPs) has also
been demonstrated. Pd@CSP has been reused in water as well as
in DMF for up to four cycles with excellent yields. On the other
hand, few aryl iodides have been studied for Ullmann coupling
reactions in pure water with the assistance of PTC under green
(weak base, air and phosphine free conditions) reaction con-
ditions, as it completely avoids the usage of such strong mineral
bases (NaOH and KOH) as well as an external reducing agent
(HCOONa and NaOMe).
Results and discussion
The TEM image in Fig. 1 shows that the synthesized Pd NPs on
CSP are well distributed with an average size of 12 0.5 nm and
the size of CSP is typically 400–600 nm. CSP is readily dispersi-
ble in solvents of different polarity without any prior surface
modifications due to its typical nature. This clearly demonstrates
that the surface of CSP is polarized with hydrophobic and hydro-
philic functionalities as shown in Fig. 2. TGA analysis showed
that the negligible decrease in catalyst weight at 100–120 °C
may be attributed to the loss of sorbed water molecules by eva-
poration (ESI†). Temperature programmed desorption of
ammonia (NH3-TPD) shows that the broad ammonia desorption
profile in the range of 280–600 °C is observed. The broad peak
is an indication of the presence of –COOH functional groups
(ESI†). XPS analysis of the Pd@CSP catalyst indicated that it
exclusively contains Pd(0). The catalytic activity of Pd@CSP
was examined for various Heck and Ullmann coupling reactions
under phosphine free and aerobic conditions.
The initial screening of the reaction was carried out not only
on the basis of high yield, but also by considering the green reac-
tion conditions (lower E-factor; Table 1, ESI†). The eco-friendly
Heck coupling reaction between iodobenzene and styrene in
water with the aid of PTC (TBAB) afforded 90% yield of the
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Despite extensive experimentation, all attempts include the aryl
bromides as electrophiles in the case of styrene in water have
failed. In addition, the reaction takes place selectively at the iodo
functionality of aryl halides as in case of 1-chloro-4-iodobenzene
(Table 1, entry 5), wherein complete chemoselectivity is
achieved for the Heck reaction. The reactions of aryl halides
with styrene at 50 °C are unsatisfactory and the yields are rela-
tively low, 25% (Table 1, entry 1). The catalyst showed improved
functional group tolerance to afford good to excellent yields of
the products with different aryl iodides. Some of the heterocyclic
halides also reacted smoothly and obtained good yields for the
Heck coupling reaction in water as well as in DMF (Table 1,
entries 8, 9 and Table 2, entries 3, 4). Among the bases used,
K2CO3, Na2CO3, Et3N, TBA, IPA, NaOH and NaOAc, all gave
excellent yields except NaOH and NaOAc, as shown in Table 3.
It was observed that Pd NPs precipitated out of the solution
when a strong base was used.56 It is proposed that the dissolution
of the Pd species from the surface of the solid-support or the Pd
clusters leads to the formation of the active species in the sol-
ution, and Pd is redeposited on the support or on the Pd clusters
as the reaction system cools down.57,58
Fig. 2 Sonicated solution of Pd@CSP in toluene (a) and water (b).
Then, we carried out the coupling reaction of iodobenzene
with styrene in DMF. It was found that DMF in combination
with Et3N as the base gives 98% isolated yield (Table 2, entry 1)
in 1 h. Avariety of aryl iodides, aryl bromides and aryl chlorides
react with various styrene, acrylic acid, acrylate, and its deriva-
tives to give the required products with moderate to excellent
yields (30–98%, Table 2). These good yields were attributed to
the hydrophobic interactions among the precursors used and
proves the importance of surface polarity of the carbon spheres
towards usage of solvents with different polarities. A combi-
nation of DMF–H2O (9 : 1) solvent system was employed, pro-
viding improved yields and selectivities for activated aryl
bromides. The fact that leached Pd is active in the aqueous co-
solvent compared to organic solvents alone might be due to
traces of water which stabilizes Pd(II) in solutions. Hence, the
water was used not only to solubilize the base, but also to
enhance the catalytic activity. Among the bases used, K2CO3,
Na2CO3, Et3N, TBA, IPA, NaOH and sodium acetate gave excel-
lent yields except NaOH and NaOAc in DMF, as depicted in
Table 3. When the catalyst loading was reduced to 0.05 mol%,
the time taken to complete the reaction was 8 h (Table 2, entry
1). Furthermore, we also investigated the recycling of the sup-
ported Pd on a model reaction of iodobenzene with styrene
(Table 2, entry 1). The catalyst exhibited a marginal loss in
activity and required a slightly longer reaction time to achieve
similar results after the second cycle. All aryl iodides afford
good to excellent yields with more E-diastereomer in pure water
as well as in DMF.
product with 100% selectivity in 7 h (Table 1, entry 1). We then
examined this coupling reaction with a variety of aryl halides
and different alkenes, in which a reaction between aryl iodide
and acrylic acid proceeded smoothly within 1.5 h (Table 1, entry
10). Addition of PTC to the reaction mixture not only initiated
the diffusion of molecules on to the hydrophobic surface of the
sphere in water, but also stabilized the leached Pd active species.
The products were separated by simple organic extraction and
purified via crystallization. The yields obtained depended on the
“surface polarity” of both the support and water. Analysis of the
filtrate from the two consecutive reactions shows that the amount
of Pd lost in solution is of the order of parts per million
(0.4 ppm of Pd) as determined by AAS analysis. The recovered
catalyst was used in four further runs for the arylation of methyl
acrylate with iodobenzene and showed a slowly decreasing
activity upon further reuse, as shown in Fig. 3. After each run,
the supported catalyst was recovered by simple filtration and
reused directly for the next run of the reaction without further
manipulation. A plot of the kinetic analysis for the catalytic
activity of Pd@CSP is illustrated in Fig. 4, for the Heck coupling
reaction of iodobenzene and methylacrylate in H2O. The catalyst
was reused at the fourth cycle without any marked loss in the
activity. Further, the kinetic data for the “homeopathic catalysis”
(0.05 mol%) was carried out under the same reaction conditions
(ESI†). XPS analysis of the Pd@CSP catalyst after the reaction
revealed that the oxidation of Pd(0) to Pd(II) was not significant
under the reaction conditions (Fig. 5).
A variety of aryl iodides react with various alkenes, including
acrylic acid, acrylates, styrene, and its derivatives, to give the
required products in water with good to excellent yields
(∼62–95%) (Table 1). Interestingly, the ability of the Pd@CSP
to promote the coupling reaction of acrylic acid and different
acrylates with a variety of aryl halides, including activated and
non-activated aryl bromides is satisfactory, but not excellent in
the case of chlorides (Table 1). Moreover, aryl bromides are acti-
vated in DMF in the case of all types of counterparts (styrene,
acrylic acid, and acrylates) and delivered good yields (Table 2).
To examine the leaching of Pd from the solid catalyst, a hot
filtration test was performed both in pure water as well as DMF
individually for the reaction of iodobenzene with styrene to yield
∼70% of the coupling product, wherein it took 24 h for this
process. The leaching of the Pd from the CSP support was
demonstrated by performing a reaction under the typical con-
ditions, by filtering the solid after 3 h, while the mixture was still
hot. Atomic absorption spectroscopy (AAS analysis) showed
that ∼3.4 ppm of Pd was found in the filtrate. No residual Pd
was observed in the final products as determined by AAS. The
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Table 1 The Heck coupling reaction of different aryl halides with different alkenes over Pd@CSP in watera
Entry
1
Aryl halide
Product
Yieldb (%)
Time (h)
Selectivityc (Heck product/biphenyl)
100 : 0, 80 : 20,d 52 : 48,d 85 : 15e
90, 25,d 55,d 25e
7.0, 30,d 3 d,d 6.5e
2
3
4
5
6
7
87
80
82
86
82
90
6.5
10
100 : 0
98 : 2
96 : 4
95 : 5
92 : 8
100 : 0
9.0
9.0
10
11
8
9
62
68
12
12
93 : 7
95 : 5
10
11
12
13
14
15
16
17
90
88
95
91
92
70
65
57
1.5
100 : 0
100 : 0
100 : 0
98 : 2
2.5
3.0
3.0
3.0
95 : 5
10.0
11.0
12.0
98 : 2
95 : 5
90 : 10
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Table 1 (Contd.)
Entry
18
Aryl halide
Product
Yieldb (%)
76
Time (h)
10.0
Selectivityc (Heck product/biphenyl)
100 : 0
19
20
21
22
75
50
25
30
9.0
100 : 0
90 : 10
—
15.0
24.0
21.5
—
a Reaction conditions: aryl iodide (0.32 mmol), alkene (0.416 mmol), TEA (0.48 mmol), TBAB (0.32 mmol), Pd@CSP (5 mg, 0.5 mol% vs. halide)
1
and 4 mL of H2O. b Isolated yields. c Selectivity of Heck product determined by H NMR. d Reaction conducted at 50 °C. e Reaction performed in
toluene.
Fig. 4 Analysis of conversion vs. reaction time for the catalytic activity
of Pd@CSP for the Heck coupling reaction of iodobenzene and methyl-
acrylate in H2O. The conversion was monitored by GC.
aggregation during the course of the reaction. The TEM image
of the catalyst after the third cycle showed a small agglomeration
of nanoparticles. It was observed that the catalyst is very active
due to the surface polarity of the support for the Heck reaction
and can be recovered and reused for upto four cycles. The
slower solubilization of the support is observed over extended
recycling, however solubilization is much faster in DMF than in
water. The solubilization of the catalyst system in organic sol-
vents may be due to greater penetration of solvent molecules to
the hydrophobic surface under heating conditions. These hetero-
geneous catalysts showed good stability for various coupling
reactions in pure water.
Fig. 3 Recycling experiments for the Heck coupling of methyl acrylate
and iodobenzene by Pd@CSP in water.
performance of the reaction in toluene thus showed the impor-
tance of leaching for better conversion.59 It is assumed that the
support firmly binds to the Pd(II) species and prevents it from
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reactions of aryl halides using amphiphilic CSP supported Pd
NPs. Various Heck coupling reactions utilising different bases
and solvents including organic polar and non-polar solvents have
been studied. Moreover, it was demonstrated that water is the
best solvent in comparison to other organic solvent systems in
terms of catalyst activity, selectivity and stability. Furthermore,
the catalysts were reused for Heck coupling reactions in water as
well as in DMF. However, the catalysts could not be reused for
the Ullmann coupling reactions probably due to the extensive
reaction times, which led to the solubilization of most of the cata-
lyst support in water. The carboxylate functionalities present on
the carbon spheres are effective for preventing the aggregation of
the leached active Pd species during the reaction. Using amphi-
philic CSP supported Pd catalysts in Heck and Ullmann coupling
reactions in water, it has been verified that the effect of surface
polarity of the CSPs has a pronounced influence on the catalyst
activity. In fact, optimization of the E-factor for the Heck coup-
ling reaction confirmed that the use of water as the solvent is
efficient for waste reduction. It is interesting to observe that the
E-factor is 4.05 and it is significantly smaller than some other
protocols reported in the literature. The better performance of
Pd@CSP catalyst in water is attributed to the amphiphilic pro-
perty of the CSP support and the “Breslow effect”. This catalytic
method is an efficient green process for C–C bond formation
reactions which includes merits such as high yields and cost
effectiveness.
Fig. 5 XPS narrow scan for Pd (a) in fresh Pd@CSP and (b) in used
(after 2nd cycle) Pd@CSP for the Heck coupling of methyl acrylate and
iodobenzene in water.
Conventionally, external reducing agents are needed in the
Ullmann coupling reactions. Under these conditions, only two
products are identified during the Ar–I Ullmann coupling reac-
tion over different Pd-based supported catalysts. One is the target
product biphenyl (Ar–Ar) which results from the coupling reac-
tion of Ar–I. The other is the side-product benzene which results
from dehalogenation of Ar–I to Ar–H. The external reducing
agents such as HCOONa or NaOMe are used to reduce Pd(II) for
regenerating the catalyst, and the base (e.g. KOH or NaOH) is
used to neutralize the HX resulting from the reduction of
PdX2.24 For the various iodobenzenes Ullmann coupling reac-
tion in aqueous conditions, Pd@CSP exhibited good activity and
complete selectivity due to the surface polarity of the CSP
toward the desired product (biphenyl) under mild reaction con-
ditions such as a mild base (K2CO3) and without a reducing
agent (HCOONa) (Table 4). The functional groups present on
the CSP might be acting as relatively weak in situ reducing
agents for PdI2.60 However, the catalyst support could not be col-
lected for further analysis, due to the solubilization of the
support over extended reaction time. The use of NaOH as the
base instead of K2CO3 led to the formation of ∼10% of phenol,
followed by the complete quenching of the reaction due to the
lower stability of Pd NPs in the increased ionic strength of
NaOH solution resulting in ineffective protection of CSP to Pd
NPs. The surface polarity of the CSP led to improved efficiency
of this catalyst system in terms of activity, and reusability has
been observed compared to other polymeric support sys-
tems.41a,43,50,61 In addition, we have calculated and compared
the E-factor value with several supported Pd NPs catalyzed Heck
coupling reactions, which are performed in water. We excluded
water from the E-factor calculations as its inclusion would lead
to extremely high E-factors in many cases and make any mean-
ingful comparison of processes difficult.26 The result shows that
our present protocol is compares favourably with other processes
and explains the improved greenness (Table 2, ESI†).
Experimental
Synthesis of colloidal carbon spheres (CSP)
The procedure for preparing carbon spheres was in accordance
with the reported method by Sun and co-workers.62 Glucose
(4 g) was dissolved in distilled water (40 mL) by stirring for
0.5 h, and then the solution was placed in a 40 mL Teflon-sealed
autoclave and maintained at 180 °C for 6–8 h. The final product
was isolated by centrifugation, cleaned by three cycles of cen-
trifugation/washing/redispersion in water and in ethanol, and
oven dried at 60 °C for 8 h.
Synthesis of CSP supported Pd nanoparticle catalysts
The synthesis of the CSP supported Pd NPs is reported in the
literature.63 Briefly, carbon spheres (50 mg) were dispersed in
absolute EtOH (25 mL) by sonicating for 30 min. Then, PdCl2
(13 mg) was added into the above suspension, followed by react-
ing at 70 °C for 1 h under vigorous stirring. After, the reaction
mixture was centrifuged, washed twice with distilled water, and
dried at 60 °C for 12 h. AAS analyses showed that 3.8 wt% of
Pd was found in the CSP supported Pd nanoparticle catalyst.
Typical reaction procedure for the Heck reaction in H2O
The Pd catalyst (5 mg, 0.5 mol% of Pd@CSP) was added to the
reaction vessel with 4 mL of H2O, sonicated for 5 min. Then,
the aryl halide (0.32 mmol), vinylating agent (0.416 mmol),
TEA (0.48 mmol), and TBAB (0.32 mmol) were mixed in cata-
lyst suspension. The reaction mixture was heated to 90 °C and
Conclusions
In conclusion, we have explored an efficient heterogeneous cata-
lyst system for the water mediated Heck and Ullmann coupling
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Table 2 The Heck coupling reaction of different aryl halides with different alkenes over Pd@CSP in DMFa
Entry
1
Aryl halide
Product
Yieldb (%)
Time (h)
Selectivityc (Heck product/biphenyl)
100 : 0, 100 : 0d, 95 : 5e
98, 90d, 80e
1.0, 8.0d, 2.0e
2
3
4
97
75
80
2.0
8.0
7.0
95 : 5
90 : 10
92 : 8
5
85
80
80
82
75
93
6.0
7.0
8.0
6.0
8.0
1.0
79 : 21
75 : 25
78 : 22
75 : 25
85 : 15
100 : 0
6
7
8
9
10
11
12
13
14
15
16
17
96
95
96
95
82
90
62
2.0
1.0
1.5
1.5
4.0
6.0
7.0
100 : 0
100 : 0
98 : 2
94 : 6
85 : 15
85 : 15
78 : 22
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Table 2 (Contd.)
Entry
18
Aryl halide
Product
Yieldb (%)
89
Time (h)
5.0
Selectivityc (Heck product/biphenyl)
90 : 10
19
20
21
22
91
63
30
32
5.0
90 : 10
78 : 22
—
10.0
22.0
20.0
—
a Reaction conditions: aryl halide (0.32 mmol), alkene (0.416 mmol), TEA (0.64 mmol), Pd@CSP (5 mg, 0.5 mol% vs. halide) and 4 mL of DMF.
b Isolated yields. c Selectivity of Heck product determined by 1H NMR. d 0.05 mol% of Pd@CSP was used. e Isolated yield and time at 3rd cycle.
Table 3 Screening of several bases in different solvents for Heck coupling of iodobenzene with styrene
Yielda (%)
H2Ob,c
Time (h)
H2Ob,c
Selectivity
H2Ob,c
Entry
Base
DMFb,d
DMFb,d
DMFb,d
1
2
3
4
5
6
7
8
TEA
TBA
IPA
K2CO3
Na2CO3
NaOAc
K3PO4
NaOH
90
88
84
83
85
7
98
96
90
90
92
5
7.0
7.0
7.5
6.5
6.5
8.0
7.5
7.5
1.0
1.0
1.5
1.5
1.5
7.0
2.0
—
100 : 0
95 : 5
95 : 5
93 : 7
93 : 7
—
100 : 0
98 : 2
98 : 2
93 : 7
93 : 7
—
75
10
72
—
94 : 6
—
96 : 4
—
a Isolated yields. b Reaction conditions: Pd@CSP (5 mg, 0.5 mol% vs. halide) and 4 mL of H2O or DMF, under air, heated at 90 °C for H2O or DMF
respectively. c Aryl halide (0.32 mmol), alkene (0.416 mmol), TEA (0.48 mmol), TBAB (0.32 mmol). d Aryl halide (0.32 mmol), alkene
(0.416 mmol), TEA (0.64 mmol).
the progress of reaction was monitored by TLC. After com-
pletion of the reaction, the reaction mixture was allowed to cool
at 0 °C for 1 h. For isolation of the solid products, first the reac-
tion mixture was filtered by rinsing with cold water (3 × 5 mL)
to remove the excess TEA, TBAB and salts formed during the
course of reaction. In the next step, the catalyst was separated
out by filtration and thoroughly washed with cold ethanol
(3 mL). However for isolation of the liquid products (Table 1,
entries 12, 13, 14, 16, and 17), the catalyst was first separated
out by filtration and thoroughly washed with water followed by
hexane (4 mL). Then, the collected organic portions in both
cases were dried over anhydrous Na2SO4, concentrated under
reduced pressure and the residue was purified by flash
chromatography using 250–400 mesh silica and hexane alone or
a mixture of ethyl acetate and hexane as eluent. The organic sol-
vents used for the purification were recycled under reduced
pressure and reused successfully. Isolated yields and purity of
the product were confirmed by 1H NMR.
Typical reaction procedure for the Heck reaction in polar
organic solvent
The Pd catalyst (5 mg, 0.5 mol% of Pd@CSP) was added to the
reaction vessel with 4 mL of DMF and sonicated for 5 min.
Then, the aryl halide (0.32 mmol), vinylating agent
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Table 4 Ullmann coupling reactions of aryl iodides over Pd@CSP in
residue was purified by flash chromatography by using
250–400 mesh silica and hexane alone or a mixture of ethyl
acetate and hexane as eluent. The organic solvents used for the
purification was recycled under reduced pressure and reused suc-
cessfully. Isolated yields and purity of the product were
confirmed by 1H NMR.
watera
Entry
R group
Time (h)
Yieldb (%)
Acknowledgements
1
2
3
4
5
6
H
22
20
20
24
21
23
52
55
53
50
44
48
p-NO2
p-CHO
p-Me
p-Cl
V.S., B.N.S., and N.M.K., are thankful to CSIR, New Delhi, for
the award of research fellowships.
p-OMe
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