Pd/Mg-La mixed oxide catalyzed oxidative sp2 CH bond acylation with alcohols

Article abstract of DOI:10.1016/j.molcata.2013.08.020

Pd/Mg-La mixed oxide is used as an efficient catalyst for the oxidative direct acylation of arene sp² CH bonds with alcohols. TBHP was used for in situ oxidation of the alcohols to aldehydes which after coupling with 2-aryl pyridines forms aryl ketones. The catalyst is recovered and used for four cycles.

Full text of DOI:10.1016/j.molcata.2013.08.020

Journal of Molecular Catalysis A: Chemical 379 (2013) 213–218
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Pd/Mg–La mixed oxide catalyzed oxidative sp2 C H bond acylation
with alcohols
R. Kishorea, M. Lakshmi Kantama,∗, J. Yadavb, M. Sudhakara, S. Lahab, A. Venugopala,∗
a Catalysis Laboratory, Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Andhra Pradesh, India
b ICIQ – Institut Català d‘Investigació Química, Avgda. Països Catalans 16, 43007 Tarragona, Spain
a r t i c l e i n f o
a b s t r a c t
Pd/Mg–La mixed oxide is used as an efficient catalyst for the oxidative direct acylation of arene sp2
bonds with alcohols. TBHP was used for in situ oxidation of the alcohols to aldehydes which after coupling
with 2-aryl pyridines forms aryl ketones. The catalyst is recovered and used for four cycles.
© 2013 Elsevier B.V. All rights reserved.
C H
Article history:
Received 12 June 2013
Received in revised form 19 August 2013
Accepted 20 August 2013
Available online 29 August 2013
Keywords:
Pd
Mg–LaO mixed oxide
Heterogeneous
Oxidative sp2
C H bond acylation
Reusability
1. Introduction
Aryl ketones have a wide range of applications in many areas
such as pharmaceuticals, fragrances and dyes [36]. Aryl ketones
One of the most important mission for synthetic chemists
is the development of new, more efficient, environmentally
benign, air and moisture stable direct transformations that allows
reduced number of synthetic operations [1–3]. In this regard,
are also used as building blocks in the synthesis of agrochemi-
cals. Synthesis of aryl ketones is performed mainly by classical
Friedel–Crafts acylation of aromatic compounds catalyzed by cor-
rosive AlCl3 or by the oxidation of the corresponding secondary
alcohols by stoichiometric amounts of toxic oxidizing reagents such
as chromium [37].
The direct incorporation of carbonyl functional groups into the
aromatic motifs through the transition metal catalyzed C H bond
cleavage will be an attractive synthetic strategy since it will be more
environmentally compatible, regioselective and complimentary to
the classical Friedel–Crafts acylation. However, the transition metal
catalyzed aryl C H bond reactions with acyl C H bond remains a
highly challenging area.
direct conversion of
C H bonds into C C bonds is highly
attractive since they would increase the atom efficiency of the
transformations [4,5].
The transition-metal-catalyzed C H activation reactions have
seen great progress [6–10] and many interesting results such as
arene C H bond cleavage to realize C C [11–20] and C X [21–27]
bond formations have been reported. Scheuermann et al. and others
[28,29] have reported the formation of C C bonds directly from two
different C H bonds through a cross-dehydrogenative coupling
reaction catalyzed by transition metals in the presence of oxidizing
reagents. Remarkable selectivity in the C C bond formation has
been achieved with the C H bonds adjacent to a heteroatom or
an unsaturated C C bond catalyzed by transition metals [30–35].
Recently, much effort has been put to realize the formation of
arene arene bonds through the oxidative coupling of two different
aryl C H bonds [29].
Li et al. [38,39] and others [40–43] have reported the oxida-
tive sp2
C H bond acylation of 2-phenylpyridine derivatives with
aromatic and aliphatic aldehydes and alcohols [44] using Pd(OAc)2
catalyst at a reaction temperature of 140 ◦C for 24 h under homo-
geneous conditions. Very recently, Wu et al. [45] have reported
ortho-acylation of 2-aryl pyridine derivatives using arylmethyl
amines as new acyl sources by using PdCl2 as a homogeneous cat-
alyst. On industrial perspective, heterogeneous catalytic process
has advantage over homogeneous in view of its ease of handling,
simple workup and recoverability. Earlier Figueras et al. reported
the synthesis and use of highly basic Mg–La mixed oxide cata-
lyst for various reactions like direct condensation of alcohols [46]
∗
Corresponding author. Tel.: +91 40 2719 3510; fax: +91 40 2716 0921.
E-mail addresses: mlakshmi@iict.res.in, lkmannepalli@gmail.com,
akula@iict.res.in (M.L. Kantam).
1381-1169/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2013.08.020

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R. Kishore et al. / Journal of Molecular Catalysis A: Chemical 379 (2013) 213–218
Table 1
Optimization of reaction conditionsa.
N
N
Pd(II)/Mg-La,
OH
O
TBHP (5equiv.)
PhCl, 120 oC, 8h
Entry
Oxidant/equiv.
Solvent
Temperature (◦C)
Yield (%)
1
2
3
4
5
6
7
8
9
TBHP/3 equiv.
TBHP/3 equiv.
TBHP/3 equiv.
TBHP/5 equiv.
TBHP/3 equiv.
TBHP/5 equiv.
TBHP/3 equiv.
K2S2O8/3 equiv.
H2O2/3 equiv.
TBHP/5 equiv.
DMSO
DMF
Chloro benzene
Chloro benzene
Water
140
140
120
120
100
100
100
120
120
120
0
0
60
82
55
55
60
0
Water
No solvent
Chloro Benzene
Chloro Benzene
No solvent
Fig. 1. XRD patterns of the Pd(II)/Mg–La mixed oxide: [a] fresh and [b] used catalysts.
0
70
10
a
0.2 mmol 2-phenylpyridine, 1 mmol benzyl alcohol, 30 mg Pd(II)/Mg–La cata-
and Michael addition reactions [47] under heterogeneous condi-
tions. Moreover, we have demonstrated the catalytic activity of the
Mg–La mixed oxide in the condensation of aldehydes and imines
with ethyl diazoacetate using DMF as a solvent [48]. Very recently,
we have explored the activity of Pd(0)/Mg–La mixed oxide cata-
lyst towards the chemoselective hydrogenation of olefinic double
bonds under heterogeneous conditions [49]. In continuation of our
studies, we report the use of Pd(II)/Mg–La mixed oxide as a hetero-
geneous and reusable catalyst for the oxidative direct acylation of
sp2 C H bonds of 2-phenylpyridine derivatives with alcohols using
TBHP as the oxidant.
lyst.
2. Experimental
2.1. Materials and methods
All reagents were commercial grade materials and were used
without further purification. All solvents were dried and distilled
by standard methods as described in the literature. Thin layer chro-
matography was performed on pre-coated silica gel 60-F254 plates.
Fig. 2. The XPS spectra of (Pd 3d5/2, 3d3/2) [a] fresh and [b] used Pd(II)/Mg–La mixed oxide catalysts.
Fig. 3. TEM images of the Pd(II)/Mg–La mixed oxide: [a] fresh and [b] used catalyst (recovered after 4th cycle).

R. Kishore et al. / Journal of Molecular Catalysis A: Chemical 379 (2013) 213–218
215
Table 2
Substrate scope of oxidative acylation of 2-phenylpyridine with different alcohols.
N
N
O
+
R
O H
R
Entry
Alcohol
Product
Yield (%)
82
N
OH
O
1
2
3
N
OH
O
80
70
N
OH
O
MeO
F
OMe
F
N
N
N
OH
OH
O
O
4
5
6
80
77
60
Cl
Br
Cl
OH
O
Br
N
OH
O
7
8
9
75
70
70
OH
OH
N
N
O
O
OMe
OMe
N
N
N
N
O
O
O
O
OH
10
11
12
13
53
67
67
65
OH
OH
OH
aReaction conditions: 0.2 mmol 2-phenylpyridine, 1 mmol benzyl alcohol, 30 mg catalyst, 1 mmol TBHP (70% in water solution), chlorobenzene (0.5 mL), 120 ◦C, 8 h.

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R. Kishore et al. / Journal of Molecular Catalysis A: Chemical 379 (2013) 213–218
100
80
60
40
20
0
by 1H NMR and 13C NMR spectroscopy. The recovered catalyst was
used for the next cycle without any further purification.
3. Results and discussion
3.1. Catalyst characterization
The XRD patterns of the fresh and used Pd/MgLa mixed
oxide catalysts (Fig. 1) results revealed that the presence of
both La2O2(CO3) and PdO phases. Diffraction lines appeared at
2ꢀ = 29.55◦, 22.84◦, 13.1◦, 30.82◦, [ICDD # 23-0435] and their corre-
sponding ‘d’ values 0.302, 0.389, 0.675 and 0.289 nm is attributed
to the lanthanum oxide carbonate phase. The diffraction peaks
observed at 2ꢀ = 31.70◦, 45.54◦, 27.33◦ [ICDD # 46-1211] and the
‘d’ values of 0.282, 0.199, 0.326 nm is indicative of PdO phase.
The XPS analysis of the fresh and used (after 4th cycle)
Pd(II)/MgLa mixed oxide catalyst is presented in Fig. 2. The PdO
species are present on the surface which was confirmed by XPS
signal appeared at binding energies 336.41 eV and 341.87 eV of Pd
3d5/2 and Pd 3d3/2 respectively over fresh catalyst and 336.87 eV
and 342.75 eV of 3d5/2 and 3d3/2 over used catalyst.
Cycle 1
Cycle 2
Cycle 3
Cycle 4
Fig. 4. Recyclability of catalyst.
The 1H NMR and C NMR spectra were recorded on 200, 300 and
500 MHz spectrometer. Chemical shifts (ı) are reported in ppm,
using TMS as an internal standard. XPS spectra were recorded on
a KRATOS AXIS 165 equipped with Mg K␣ radiation (1253.6 eV)
at 75 W apparatus using Mg K␣ anode and a hemi spherical ana-
lyzer. The C 1s line at 284.6 eV was used as an internal standard
for the correction of binding energies. The X-ray diffraction (XRD)
patterns of the fresh and used samples were obtained on a Rigaku
Miniflex X-ray diffractometer using Ni filtered Cu K␣ radiation
The transmission electron microscopic (TEM) pictures of the
fresh and used (after 4th cycle) Pd/Mg–La mixed oxide catalysts
Table 3
Substrate scope of oxidative acylation of different 2-phenylpyridine derivatives with
benzyl alcohol.
(ꢀ = 0.15406 nm) from 2ꢀ = 10 to 80◦, at a scan rate of 2◦ min−1
,
with the beam voltage and beam current of 30 kV and 15 mA
respectively.
2.2. Preparation of catalyst
Pd(II)/Mg–La catalyst was prepared following
a
modified
.
procedure of the previous work reported by Figueras et al.
[50] Mg–La mixed oxide was obtained by co-precipitation of
Magnesium nitrate (Mg(NO3)2·6H2O) and Lanthanum nitrate
(La(NO3)3·6H2O). A solution containing 0.386 mol magnesium
nitrate (Mg(NO3)2·6H2O) and 0.129 mol lanthanum nitrate
(La(NO3)3·6H2O) dissolved in 0.5 L water for an atomic ratio
Mg/La = 3, was precipitated by using mixture of KOH (1 mol)
and K2CO3 (0.26 mol) in 0.52 L of distilled water maintained at a
constant pH 10. The solid was filtered, washed with distilled water,
dried at 373 K and calcined at 923 K for 5 h. The Mg–La mixed
oxide (1.5 g) was suspended in 150 mL of aqueous palladium (II)
nitrate hydrate (Pd (NO3)2·xH2O) [0.345 g, 1.5 mmol] solution
and stirred at 25 ◦C for 12 h under a nitrogen atmosphere. The
solid was filtered, washed with distilled water, dried at 373 K
and calcined at 923 K for 5 h. The BET-surface area of the calcined
Pd/Mg–La sample is found to be 47.5 m2 g−1 and the pore volume
Entry
1
2-Arylpyridine
Product
Yield (%)
82
O
O
N
N
O
Ph
N
2
80
N
O
Ph
F
F
N
3
4
5
6
70
80
77
60
N
O
Ph
Cl
Br
Cl
N
O
is 0.123 cc g−1
.
N
Ph
Ph
2.3. General procedure for the oxidative sp2
with alcohols
C H bond acylation
Br
N
O
N
In a typical reaction, a 10 mL oven-dried reaction vessel was
charged with Pd/MgLa mixed oxide (30 mg), 2-phenylpyridine
(29 mg, 0.2 mmol), benzyl alcohol (108 mg, 1 mmol), tert-butyl
hydroperoxide (70% solution in water, ∼129 mg, 1 mmol) and
chlorobenzene (0.5 mL) were added. The resulting solution was
stirred at 120 ◦C for 8 h in open air. The reaction was monitored by
thin-layer chromatography (TLC). After cooling to room tempera-
ture, catalyst was separated by simple centrifugation. The filtrate
was concentrated under reduced pressure and the residue was
purified by column chromatography using silica gel and a mixture
of hexane/ethyl acetate as eluents. All the products were confirmed
F3C
N
F3C
O
N
Ph
N
7
75
O
N
Ph
aReaction conditions: 0.2 mmol 2-phenylpyridine, 1 mmol benzyl alcohol, 30 mg
catalyst, 1 mmol TBHP (70% in water), chlorobenzene (0.5 mL) 120 ◦C, 8 h.

R. Kishore et al. / Journal of Molecular Catalysis A: Chemical 379 (2013) 213–218
217
Scheme 1. Plausible reaction mechanism.
are reported in Fig. 3[a] and [b]. The Pd particle size was measured
from TEM images (Fig. 3) and found to be 19.3 and 23.9 nm for fresh
and used catalysts respectively.
fluoro, bromo, trifluoromethyl were tolerated under the optimal
reaction conditions and the desired products were obtained in
moderate to good yields. When benzo[h]quinoline was subjected
to the procedure, a 54% yield of the acylation product was isolated
(Table 3, entry7).
3.2. Catalytic activity of Pd/Mg–La mixed oxide catalyzed
oxidative sp2
C H bond acylation with alcohols
3.3. Recyclability
When polar solvents such as DMSO and DMF were used, sur-
prisingly no product formation was observed. However, we are
delighted to find that using chlorobenzene as the solvent at a tem-
perature of 120 ◦C produced the desired product about 60% yield
using 3 equiv. of 70% aqueous solution of TBHP (Table 1, entry 3).
Upon increasing the amount of TBHP (5 equiv.) the yield of the prod-
uct increased to 82% (Table 1, entry 4). The reaction gave 55% yield
of the product using water (Table 1, entry 5). However, increasing
the amount of TBHP from 3 to 5 equiv. did not show any effect on
the product yield for the reaction carried in water (Table 1, entry 6).
The reaction was also carried out under solvent free condition using
3 equiv. of TBHP and interestingly 60% yield of the product forma-
tion was observed (Table 1, entry 7). Next we studied the effect
of different oxidizing agents on the acylation reaction. The reac-
tion failed when K2S2O8 and H2O2 were used as oxidizing agents.
Therefore, among the various optimization studies performed, the
most promising result obtained is shown in Table 1 entry 4.
A preliminary study on the catalytic activity of Pd/Mg–La mixed
oxide for the oxidative acylation of 2-phenylpyridine and benzyl
alcohol was performed using TBHP as the oxidant and the results
are summarized in Table 1. Performing the reaction on various alco-
hols and 2-phenylpyridine under the optimized reaction condition
produced yields ranged between 53 and 82% (Table 2). A lower
yield of the desired product was obtained when sterically bulky
ortho-substituted benzyl alcohol was used (Table 2, entry 7). To
our delight, this reaction is not limited to benzyl alcohol and its
derivatives. More challenging aliphatic alcohols such as 1-hexanol
and 1-octanol were also reactive towards 2-phenylpyridines which
resulted in 53% and 67% yields of the desired products respectively
(Table 2, entry 10 and 12). It should be noted that the reaction gave
the mono acylation product selectively in all cases. The results of
2-phenyl derivatives with benzyl alcohol are presented in Table 3.
A series of functional groups including methyl, methoxy, chloro,
The recyclability of the catalyst was examined using 2-
phenylpyridine and benzyl alcohol at 120 ◦C in TBHP under
chlorobenzene as solvent and the results are shown in Fig. 4, which
clearly illustrates that the catalyst can be used for four consecu-
tive cycles with consistent yields and selectivity. In the recyclability
studies, catalyst was recovered by simple centrifugation. The recov-
ered catalyst was washed, air-dried and used directly for the next
cycle without any further purification. The ICP-MS analysis showed
that the Pd(II) content of fresh and used is 9.1% and 8.9% respec-
tively. From this we can conclude that there no significant leaching
of Pd.
3.4. Plausible mechanism
A
proposed mechanism to rationalize this transformation
is illustrated in Scheme 1. The reaction proceeds through the
chelation-directed C H activation of 2-phenylpyridine by active
palladium catalyst to generate intermediate (A) Then the reaction
of A with TBHP generates intermediate (B) which in turn reacts
with the aldehyde which is produced from the oxidation of alcohol,
forming the acyl intermediate (C). Finally, intermediate (C) under-
goes reductive elimination to produce the coupling product and
regenerates palladium catalyst for further reactions.
4. Conclusions
In conclusion, we have developed a simple and efficient method
for the oxidative sp2
C H bond acylation of 2-phenylpyridine
derivatives using alcohols and TBHP as the oxidizing agent and
Pd/Mg–La mixed oxide as heterogeneous catalyst. The catalyst can
be readily recovered and reused for four consecutive cycles with
consistent activity and selectivity.

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R. Kishore et al. / Journal of Molecular Catalysis A: Chemical 379 (2013) 213–218
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