Polystyrene-supported Pd(II) complex-catalysed carboacylation of 2-arylpyridines with alcohols via C─H bond activation under solvent-free conditions

Article abstract of DOI:10.1002/aoc.3581

Polystyrene-supported N,N-dimethylethylenediamine Pd(II) complex C was used as an efficient catalyst for the synthesis of aromatic ketones via ortho-acylation of sp² C─H bonds of 2-arylpyridines with alcohols as effective coupling partners. The alcohols were oxidized with tert-butyl hydroperoxide to their corresponding aldehydes in situ and efficiently coupled with 2-arylpyridines to form aryl ketones under solvent-free conditions. Furthermore, catalyst C could be easily recovered by simple filtration and reused for five cycles without any significant decrease in its activity.

Full text of DOI:10.1002/aoc.3581

Received: 26 May 2016
DOI 10.1002/aoc.3581
Revised: 7 July 2016
Accepted: 8 July 2016
F U L L PA P E R
Polystyrene‐supported Pd(II) complex‐catalysed carboacylation of
2‐arylpyridines with alcohols via C─H bond activation under
solvent‐free conditions
1
1
Pullaiah C. Perumgani | Sai Prathima Parvathaneni | Srinivas Keesara2 |
*
1
*
Mohan Rao Mandapati
1 Catalysis Laboratory, Inorganic and Physical
Chemistry Division, CSIR – Indian Institute of
Chemical Technology (IICT), Tarnaka, Hyderabad
500 607, India
2 School of Chemistry, University of Hyderabad,
Hyderabad 500 046, India
Polystyrene‐supported N,N‐dimethylethylenediamine Pd(II) complex C was used as
an efficient catalyst for the synthesis of aromatic ketones via ortho‐acylation of sp2
C─H bonds of 2‐arylpyridines with alcohols as effective coupling partners. The
alcohols were oxidized with tert‐butyl hydroperoxide to their corresponding alde-
hydes in situ and efficiently coupled with 2‐arylpyridines to form aryl ketones under
solvent‐free conditions. Furthermore, catalyst C could be easily recovered by simple
filtration and reused for five cycles without any significant decrease in its activity.
Correspondence
Sai Prathima Parvathaneni and Mohan Rao
Mandapati, Catalysis Laboratory, Inorganic and
Physical Chemistry Division, CSIR – Indian
Institute of Chemical Technology (IICT), Tarnaka,
Hyderabad – 500 607, India.
KEYWORDS
Email: saiprathimaiict@gmail.com;
alcohols, C─H activation, carboacylation, palladium(II) complex, solvent‐free
conditions
mandapati@iict.res.in
1
|
INTRODUCTION
sp2 C─H bond acylation is highly advantageous over the
existing methods for aryl ketone synthesis. To date several
Design and development of efficient, eco‐economical,
green pathway for direct conversion of C─H bonds into
C─C bonds via C─H bond activation with reduced num-
ber of synthetic operations has become an important tar-
get in organic synthesis.[1–3] Directing group‐assisted
C─H bond functionalization and cross dehydrogenative
coupling are commonly employed strategies due to their
being atom‐ and step‐economic for achieving selective
functionalizations.[4–6] Transition‐metal‐catalysed C─H
activation and subsequent C─H bond functionalization
has achieved great progress in modern synthetic chemis-
try.[7–11] Ru, Rh, Cu and Pd are commonly employed
metals for carbon–carbon bond forming processes.[12,13]
Palladium complexes are particularly attractive catalysts
for ligand‐directed C─H functionalization reactions.[14,15]
Their versatility is mainly due to the high compatibility
of Pd(II) catalysts with oxidants and their exceptional sta-
bility towards moisture and air.
research groups have developed transition‐metal‐catalysed
sp2 C─H bond acylations with aldehydes, toluenes,
diketones, carboxylic acids, arylmethylamines and benzylic
ethers as acyl sources.[17–22] However, oxidative acylation
at aromatic sp2 C─H bonds with the use of transition metal
and employing alcohols as acyl source is extremely rare. Li
and co‐workers recently reported oxidative ortho‐acylation
of arylpyridines with benzylic and aliphatic alcohols as acyl
source through palladium‐catalysed C─H bond activa-
tion.[23] Yuan et al. also reported C─H bond acylation of
acetanilides with benzylic alcohols by employing palladium
catalyst.[24] Recently, Kim and co‐workers demonstrated
Pd‐catalysed oxidative sp2 C─H bond acylation of N‐
benzyltriflamides, 2‐phenoxypyridines, ketoximes and
aldoximes with alcohols as coupling partners.[25–27] Most
of the methods for C─H bond acylation are reported under
homogeneous conditions. The main advantage of the poly-
meric Pd(II) complex (C) presented here over existing
methods is mainly less catalytic loading, better recyclability,
broad scope with excellent yields and ease of preparation of
the catalyst. From green and industrial perspectives hetero-
geneous catalysis is advantageous in view of its ease of
Aryl ketones are prominent structural functionalities in
the fragrance, dye and pharmaceutical industries.[16] From
economic and environmental points of view, direct introduc-
tion of carbonyl functional groups onto aromatics through
Appl. Organometal. Chem. 2016; 1–6
wileyonlinelibrary.com/journal/aoc
Copyright © 2016 John Wiley & Sons, Ltd.
1

2
PERUMGANI ET AL.
handling with high recyclability. Recently polystyrene‐
supported transition metal complexes have received much
attention in the area of heterogeneous catalysis owing to low
cost, chemical inertness with facile functionalization.[28–33]
Our research mainly focused on developing simple, eco-
nomic, green pathways for C─C bond formation reactions.
In view of the continuing interest in developing simple
recyclable polymer‐bound metal complexes, we reported
polystyrene‐supported Pd(II)–N,N‐dimethylethylenediamine
complex C and its application to the Suzuki–Miyaura cross‐
coupling reaction in water.[34]
(Hz). Mass spectra were recorded with a mass spectrometer
using the electron spray ionization (ESI) and the data
acquired in positive ionization mode. High‐resolution MS
(HRMS) was conducted with a TOF‐type mass analyser.
Fourier transform infrared spectra of samples were recorded
with a PerkinElmer FTIR 783 spectrophotometer using KBr
pellets. An EXSTAR TG/DTA7200 instrument was used for
thermogravimetric analysis. The metal content in the cata-
lyst was determined using a Varian AA240 atomic absorp-
tion spectrophotometer.
Herein we report the complex C‐catalysed ortho‐acyla-
tion of 2‐phenylpyridines by employing alcohol derivatives
as simple coupling partners. As alcohols are naturally
abundant and can be readily oxidized in situ into alde-
hydes, we selected alcohols as carbonyl source.[31] The
ortho‐acylation product was obtained in excellent yields
using the recyclable, heterogeneous palladium complex
under solvent‐free conditions with alcohol as an acylating
partner (Scheme 1). This protocol is highly desirable due
to it being atom‐ and step‐economic for the direct conver-
sion of C─H bonds to C─C bonds for aryl ketone
synthesis.
2.2 | General procedure for carbonylation catalysed by
polymer‐anchored Pd(II) complex (C)
A dried round‐bottomed flask equipped with a magnetic stir
bar was charged with 25 mg of polymer‐anchored Pd(II) cat-
alyst C, and 2‐phenylpyridine (0.5 mmol), benzyl alcohol
(1.0 mmol) and tert‐butyl hydroperoxide (TBHP; 2.0 mmol)
were added to the reaction vessel. The mixture was stirred
at 120°C for 12 h, then cooled to room temperature and the
catalyst was filtered. The filtrate was extracted with ethyl ace-
tate (3 × 10 ml). The combined organic layers were extracted
with water, and dried over anhydrous Na2SO4. The organic
layers were evaporated under reduced pressure and the
resulting crude product was purified by column chromatogra-
phy using ethyl acetate–hexane (1:4) as eluent to afford the
corresponding ortho‐acylation products. The products were
2
| EXPERIMENTAL
1
characterized using H NMR and 13C NMR spectroscopies
2.1 | Materials and instrumentation
and HRMS.
Analytical‐grade reagents and freshly distilled solvents were
used throughout the experiments. The reagents were sup-
plied by Sigma‐Aldrich Chemicals Company, USA, and
Merck Co. Liquid substrates were redistilled and dried with
appropriate molecular sieves. Distillation and purification of
the solvents and substrates were done by standard proce-
dures. The starting materials and reagents were purchased
from various commercial sources and used without further
purification. ACME silica gel (60–120 mesh) was used for
column chromatography. Analytical TLC was performed
on pre‐coated TLC plates with silica gel 60‐F254 plates
2.3 | Catalytic activity
As polymer‐anchored metal complexes exhibit efficient cat-
alytic activity with broad applicability, they have been
extensively studied and reported in the literature. In our pre-
vious work we studied the complete characterization and
their catalytic activity in the field of coupling reactions.[30]
Now we decided to investigate the catalytic activity of cata-
lyst C in the preparation of benzophenones via the carbon-
ylation reaction with alcohols without using carbon
monoxide.
1
and visualized by UV light. H NMR and 13C NMR spectra
were recorded using tetramethylsilane (TMS) in CDCl3 sol-
vent as the internal standard with a 400, 500 MHz spec-
trometer (1H NMR: TMS at 0.00 ppm, CDCl3 at
7.26 ppm; 13C NMR: CDCl3 at 77.00 ppm). Chemical
shifts were recorded in ppm with respect to TMS as an
internal standard and coupling constants are quoted in hertz
The
synthesis
of
polymer‐supported
N,N‐
is
dimethylethylenediamine‐derived Pd(II) complex
C
shown in Scheme 2. N,N‐dimethylethylenediamine‐func-
tionalized polystyrene resin B was formed by heating a
mixture of chloromethylated polystyrene and N,N‐
dimethylethylenediamine in CH3CN at 70°C for 48 h. To
SCHEME
2
Synthesis of N,N‐dimethylethylenediamine‐derived Pd(II)
SCHEME 1 Acylation of 2‐phenylpyridines catalysed by complex C
complex C

PERUMGANI ET AL.
3
B were added EtOH and Pd(CH3CN)2Cl2 in 1:1 molar ratio
which was then refluxed for 12 h. This resulted in covalent
attachment of palladium to give the functionalized polymer
complex C.
TABLE 2 Acylation reaction of 2‐phenylpyridine with a variety of benzyl
alcoholsa
Entry
Alcohol
Produt
Yield (%)
1
94
3
| RESULTS AND DISCUSSION
2
3
4
82
86
82
To initiate our study, we examined the carboacylation of
2‐phenylpyridines with alcohols in the presence of poly-
mer‐supported Pd (II) complex C under a variety of reaction
conditions. In order to establish the optimum conditions for
ortho‐acylation, we chose 2‐phenylpyridine (1) and benzyl
alcohol (2a) as model substrates (Table 1). The effect of vari-
ous oxidants on the catalytic activity of complex C has been
studied (entries 1–11). Several oxidants such as K2S2O8, O2,
TBHP, H2O2 and tert‐butyl peroxybenzoate (TBPB) were
screened at various temperatures (Table 1). However, in the
presence of K2S2O8, O2, H2O2 and TBPB the desired product
was not obtained even at 120°C for 24 h (entries 1–4). To our
delight, TBHP proved to be the best oxidant at 120°C for a
reaction time of about 12 h and desired product was obtained
in 94% yield in the presence of Pd complex C (entry 9). But
TBHP was ineffective at room temperature with no yield
(entry 5) and low yield at 80°C (entry 6). There is a consider-
able change in yields on increasing the temperature from 100
to 120°C (entries 7 and 8) and reaction time from 6 to 12 h
(entries 8 and 9). As expected the desired product was not
obtained even in trace amounts in the absence of oxidant,
TBHP and catalyst (entries 10 and 11). These optimization
5
6
7
80
78
80
8
78
75
91
TABLE 1 Screening of reaction conditionsa
9
10
Entry
Oxidant
Temp. (°C)
120
Time (h)
24
Yield (%)b
1
2
K2S2O8
—
—
—
—
—
40
73
85
94
O
2 (1 atm)
120
24
11
12
88
84
3
H2O2
TBPB
TBHP
TBHP
TBHP
TBHP
TBHP
—
120
24
4
120
24
5
RT
24
6
80
24
7
100
24
8
120
6
9
120
12
c
10
11
110
24
—
aReaction conditions: 1 (0.5 mmol), 2a (1.0 mmol), catalyst (25 mg), oxidant
(2.0 mmol), 120°C for 12 h.
d
TBHP
110
24
—
bIsolated yield.
aReaction conditions: 1 (0.5 mmol), 2a (1.0 mmol), catalyst (25 mg), oxidant
(2.0 mmol), solvent‐free.
bIsolated yield.
cNo oxidant.
dNo catalyst.
studies show that TBHP at 120°C in the presence of Pd com-
plex C for 12 h gave the desired product 3a in 94% yield under
solvent‐free conditions (Table 1, entry 9).

4
PERUMGANI ET AL.
The direct ortho‐acylation of 2‐phenylpyridine with var-
ethanol and propanol resulted in trace amounts of the desired
product (Table 3, entries 1 and 2). However, the reaction gave
the monoacylation product selectively with 1‐octanol and 1‐
decanol in (5c) 85% and (5d) 88% yields, respectively
(Table 3, entries 3 and 4).
ious alcohols was conducted under the optimized reaction
conditions, and the results are summarized in Table 2.
The reactions with benzylic alcohols bearing electron‐
donating groups (entries 1–3 and 10–12) and electron‐with-
drawing substituents at the aromatic ring (entries 4–9)
proceeded to give the desired products in good to excellent
yields. There is considerable influence on the yields for
ortho, para and meta isomers of alcohol derivatives. The
ortho isomer‐containing products had low yields (3b, 3f,
3i and 3l) when compared to para or meta isomers due
to steric hindrance (3d, 3g, 3j and 3c, 3e, 3h, 3k). How-
ever electron‐donating group‐substituted acylated products
(OMe, CH3) gave better yields than electron‐withdrawing
substituents (F, Cl and Br). The OMe‐substituted para,
meta, ortho gave (3j) 91%, (3k) 88%, (3l) 84% yields and
Me‐substituted meta, ortho resulted in (3c) 86%, (3b)
82% yields of the desired products. In the case of chloro‐
substituted para, meta, ortho the desired product was
obtained in (3d) 82%, (3e) 80%, (3f) 78% yields and
fluoro‐substituted para, meta in (3g) 80%, (3h) 78% yields,
whereas meta‐substituted bromo gave (3i) 75% yield. The
most interesting result is that Ar─Br (3i) group is tolerated
since Pd species might be expected to cleave C─Br bonds
easily.
Further, we extended scope of the reaction with vari-
ous substituted arylpyridines for the directed aroylation
of 2‐arylpyridines under the optimized reaction conditions,
and the results are presented in Table 4. Functional
groups including Me, OMe, OEt, COMe and naphthyl
were compatible and the desired products were obtained
in excellent yields. For example, arylpyridines substituted
with 4‐methyl, ethoxy and methoxy (which bears a
strong electron‐donating group) afforded the desired prod-
ucts 6a, 6b and 6c in 91, 89 and 93%, respectively.
Whereas 6d and 6e were obtained in 90 and 86% yields
and 6g in 88% yield. In the case of naphthyl‐substituted
pyridine, the desired product 6f was also obtained in
85% yield. Thus the aroylation reaction selectively gave
the monoacylated products with
phenylpyridines.
a
variety of 2‐
The recyclability of the polymer‐anchored Pd(II) com-
plex C was tested in the acylation of 2‐phenylpyridine
and benzyl alcohol. As shown in Figure 1, the catalyst
can be reused for five cycles with only 4% decline of activ-
ity after the fifth recycle. The leaching of palladium from
the polymer‐anchored Pd(II) complex C was confirmed
by carrying out atomic absorption spectroscopic analysis.
The analytical data for the used catalyst did not show
In addition we also tested the reaction with more chal-
lenging aliphatic alcohols for direct aroylation of 2‐
phenylpyridines under the optimized reaction conditions,
and the results are summarized in Table 3. It is noted that
TABLE 3 Acylation reaction of 2‐phenylpyridines with aliphatic alcoholsa
Entry
Alcohol
Product
Yield (%)b
1
trace
2
3
4
trace
85
88
aReaction conditions: 1 (0.5 mmol), 4 (1.0 mmol), catalyst (25 mg), oxidant (2.0 mmol), 120°C for 12 h.
bIsolated yield.

PERUMGANI ET AL.
5
TABLE 4 Acylation reaction of a variety of 2‐phenylpyridines with benzyl
4 | CONCLUSIONS
alcohola
In view of minimizing the waste/side product formation for
acylation with benzyl alcohol for (hetero)arenes bearing
ortho‐directing group, we have developed a simple recycla-
ble Pd(II) catalyst. This heterogeneous catalyst is versatile,
active and stable, and can be reused for five cycles without
appreciable loss of activity, indicating effective anchoring of
the polymer. It is noteworthy that this heterogeneous palla-
dium complex gave the ortho‐acylation products in excel-
lent yields under solvent‐free conditions with broad
substrate scope. Thus this represents an efficient, eco‐eco-
nomical, green pathway for carbonylation/ortho‐acylation
of 2‐phenylpyridines.
Yield
Entry
2‐Phenylpyridine
Product
(%)b
1
91
2
89
3
4
5
93
90
86
ACKNOWLEDGMENTS
P.S.P. gratefully acknowledges the financial assistance pro-
vided by CSIR‐Senior Research Associateship (Scientist's
Pool Scheme), New Delhi and P.C.P. (UGC‐SRF) is grateful
for the fellowship provided by UGC, Government of India.
We also acknowledge the director IICT for providing infra-
structural facilities.
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