Polystyrene supported Dichloro-(8-aminoquinoline)-Palladium(II) complex catalyzed C[sbnd]H bond activation for ortho-acylation of 2-aryl pyridines

Article abstract of DOI:10.1016/j.ica.2016.10.014

Polystyrene-supported Dichloro-(8-aminoquinoline)-Pd(II) complex C was synthesized and its catalytic efficiency was evaluated for ortho-acylation of 2-aryl pyridines with alcohols to form aryl ketones via cross dehydrogenative coupling. In addition in the presence of Pd(II) complex, toluene derivatives were also employed as an effective coupling partner for synthesis of aromatic ketones. Furthermore, this catalyst was highly stable and could be easily recovered by simple filtration and reused for four cycles with no significant decrease in its activity and selectivity.

Full text of DOI:10.1016/j.ica.2016.10.014

Accepted Manuscript
Research paper
Polystyrene supported Dichloro-(8-aminoquinoline)-Palladium(II) complex
catalyzed C-H bond activation for ortho-acylation of 2-aryl pyridines
C. Pullaiah Perumgani, Sai Prathima Parvathaneni, Balaswamy Kodicherla,
Srinivas Keesara, Mohan Rao Mandapati
PII:
S0020-1693(16)30664-8
http://dx.doi.org/10.1016/j.ica.2016.10.014
ICA 17307
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
3 August 2016
3 October 2016
7 October 2016
Please cite this article as: C. Pullaiah Perumgani, S. Prathima Parvathaneni, B. Kodicherla, S. Keesara, M. Rao
Mandapati, Polystyrene supported Dichloro-(8-aminoquinoline)-Palladium(II) complex catalyzed C-H bond
activation for ortho-acylation of 2-aryl pyridines, Inorganica Chimica Acta (2016), doi: http://dx.doi.org/10.1016/
j.ica.2016.10.014
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Polystyrene supported Dichloro-(8-aminoquinoline)-Palladium(II) complex
catalyzed C-H bond activation for ortho-acylation of 2-aryl pyridines
Pullaiah Perumgani C,a Sai Prathima Parvathaneni*a, Balaswamy Kodicherla,a Srinivas Keesara,b
Mohan Rao Mandapati*a
aCatalysis Laboratory, Inorganic and Physical Chemistry Division
CSIR-Indian Institute of Chemical Technology (IICT),Tarnaka, Hyderabad –500 607, India,
bSchool of Chemistry, University of Hyderabad, Hyderabad 500046, India.
Fax: +91-040-27160921, Tel: (+) 91 40 27193181
E-mail: saiprathimaiict@gmail.com, mandapati@iict.res.in
Abstract: Polystyrene-supported Dichloro-(8-aminoquinoline)-Pd(II) complex
C
was
synthesized and its catalytic efficiency was evaluated for ortho-acylation of 2-aryl pyridines with
alcohols to form aryl ketones via cross dehydrogenative coupling. In addition in the presence of
Pd (II) complex, toluene derivatives were also employed as an effective coupling partner for
synthesis of aromatic ketones. Furthermore, this catalyst was highly stable and could be easily
recovered by simple filtration and reused for four cycles with no significant decrease in its
activity and selectivity.
N
N
H
Pd
C
N
N
Cl
Cl
O
H
OH
R
tBuOOH, 110oC, 8h
R1
+
R1
R
3
2
Scheme 1
Introduction:
Direct C-H bond functionalisation of aromatic motifs via introduction of carbonyl groups will be
a more challenging, environmentally friendly, complementary to Friedel-Crafts acylation for aryl
ketone synthesis [1]. Aryl ketones are predominantly employed in the fragrance, dye and
pharmaceutical industries [2]. Directing group assisted C-H bond functionalisation and cross
dehydrogenative coupling (CDC) are commonly employed methods to achieve selective C-H
bond functinalisations [3-5]. Ru, Rh, Cu and Pd are commonly employed transition-metals for
carbon-carbon bond forming processes [6-7]. Among these, the palladium complexes are

preferred catalysts for directed C-H functionalisation reactions due to their high compatibility
and exceptional stability towards moisture and air [8]. Recently, research group of Kim has
developed transition metal catalysed oxidative sp2 C-H bond acylations with aldehydes for
synthesis of aromatic ketones [9]. Encouraged by these findings, it further occurred to us that
alcohols can be potentially utilized as ideal acylation reagents since alcohols can be readily
oxidized into aldehydes [10]. Kim, Yuan and Li groups have reported oxidative ortho
-
acylations of aryl moieties with alcohols as acyl source through palladium-catalyzed
synthesis of aromatic ketones [11-15]. Most of the reported methods for C-H bond acylation are
under homogeneous conditions [16-18]. However, oxidative acylation on aromatic sp2 C-H
bonds with the exploitation of recyclable heterogenous catalysts are extremely rare. Thus there is
a wide scope for improvement of new heterogeneous catalysts for oxidative acylations.
Our research group mainly interested in developing simple recyclable polymer bound metal
complexes, and its applications for C-C bond formation reactions [19]. Recently, we have
reported polystyrene-supported N,N-dimethylethylenediamine with Cu and Pd complexes
(
E
and
F
) as catalysts for Sonogashira, A3, Suzuki coupling reactions and N-
for KA2 coupling (figure 1) [20-23].
phenylpiperazine-Cu(II) complex
D
Fig. 1 Polymer supported copper and palladium complexes (C, D, E and
F).
Herein, we report polymer supported Pd(II) complex C as an efficient and highly reusable
heterogeneous catalyst for ortho-acylation of 2-phenyl pyridines by employing alcohol
derivatives as the simple coupling partners. The main advantage of the present polymeric
palladium (II) C complex over existing methods is mainly less catalytic loading, better
recyclability and broad scope with excellent yields (Scheme 1).

Experimental
Material and Instruments
Analytical-grade reagents and freshly distilled solvents were used throughout the experiment.
The reagents were supplied 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 procedures. 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 thin-layer chromatography (TLC) was performed on pre-coated TLC plates with silica
1
gel 60-F254 plates and visualized by UV-light. H NMR and 13C NMR spectra were recorded,
using tetramethylsilane (TMS) in the solvent of CDCl3 as the internal standard on a 400, 500
MHz spectrometer (1H NMR: TMS at 0.00 ppm, CDCl3 at 7.26 ppm; 13C NMR: CDCl3 at 77.00
ppm). Chemical shifts (δ) were recorded in ppm with respect to TMS as an internal standard and
coupling constants are quoted in Hertz (Hz). Mass spectra were recorded on a mass spectrometer
by the electron spray ionization (ESI) and the data acquired in positive ionization mode. HRMS
spectra were determined on TOF type mass analyzer. FTIR spectra of the samples were recorded
on a Perkin-Elmer FTIR 783 spectrophotometer using KBr pellets. A EXSTAR TG/DTA7200
instrument was used for the thermogravimetric (TGA) analysis.
Preparation of polymer-supported 8-Aminoquinoline (B) (PS-8-AQ)
A 250 mL round bottom flask containing CH3CN (50mL), equipped with a magnetic stirrer bar is
added with chloromethylated polystyrene (1 g, 1.2 mmol g-1 of Cl) and 8-Aminoquinoline (5
mmol) and NaI (0.1 mmol). The reaction mixture was refluxed for 48 h and was subsequently
filtered and the residue was washed sequentially with CH3CN (3 × 20 mL), 1:1 CH3OH–1M aq
K2CO3 (3 × 20 mL), 1:1 CH3OH–H2O (3 × 20 mL), and Et2O (3 × 10 mL), and then dried in an
oven.
Preparation of polystyrene-supported Pd(II) complex (C) (PS-8-AQ-Pd)
To the polystyrene-supported 8-Aminoquinoline B (0.5g), EtOH (100 mL) was added and kept
for 30 min. A solution of Pd(CH3CN)2Cl2 (0.5 g) in EtOH (10 mL) was then added, and the (1:1)
mixture was refluxed for 12 h. The polymer-anchored brown colored metal complex,

impregnated with the metal, was filtered, washed thoroughly with EtOH (3 × 30 mL), and finally
dried in vacuum at 70 C for 24 h (Scheme 2).
°
Scheme 2. Synthesis of polymer-bound 8-Aminoquinoline derived Pd(II) complex C.
General procedure for carbonylation reaction catalyzed by Polymer anchored-Pd(II) C:
A dried round bottomed flask equipped with a magnetic stir bar was charged with 15 mg
Polymer anchored-Pd(II) C catalyst (PS-8-AQ-Pd), 2-phenyl pyridine (0.5 mmol), benzyl
alcohol (1.0 mmol) and TBHP (2.0 mmol) were added to a reaction vessel. The mixture was
ο
stirred at 110 C for 8 h, then cooled to room temperature and catalyst was filtered, the filtrate
was extracted with ethyl acetate (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 chromatography by using ethyl
acetate/hexane (1:4) as eluent to give the corresponding ortho-acylation products. The products
were characterized by 1H NMR, 13C NMR and HRMS.
Results and discussion
The new polymer supported Pd(II) catalyst C was prepared in two steps which is clearly
represented in Scheme 2. 8-Aminoquinoline functionalized polystyrene resin B was formed by
heating a mixture of chloromethylated polystyrene and 8-Aminoquinoline A in CH3CN for 48 h.
This polymer-supported 8-Aminoquinoline B is insoluble in common organic solvents. Reaction
of B with EtOH and Pd(CH3CN)2Cl2 in 1 : 1 molar ratio for 12 h resulted in covalent attachment
of palladium to give functionalized polymer anchored-Pd(II) complex C. The complex was
characterized by chemical analysis, SEM-EDX, TGA, AAS and IR spectroscopic techniques.
The complexation ratio of palladium to PS-8-AQ is 1:1. The amount of palladium incorporated
into the polymer was determined by atomic absorption spectroscopy (AAS), which showed a
value of 4.93%. This complex formation was confirmed by FT-IR analysis. In the IR spectrum of
chloromethylated polystyrene, the two characteristic peaks at 1263 and 670 cm-1 were due to
stretching and bending vibrations of C–Cl group. They were practically eliminated after the

introduction of 8-Aminoquinoline and palladium onto the polymer. Compared to the IR spectrum
of Pd(CH3CN)2Cl2, the peaks at 2330 cm–1 (C–N, CH3CN), and 2918 cm–1 (C–H, CH3CN) are
absent in the case of complex. The decrease in IR value of the NH group of polystyrene
supported ligand
B C indicates the
(from 3431 cm–1 to 3407 cm–1) to the complex
formation of Pd–N bond (Supporting information).
Fig. 2 SEM images of (a) polymer anchored ligand (PS-8-AQ); (b) palladium complex
(PS-8-AQ-Pd).
Fig. 3 EDX image of (a) polymer anchored ligand (PS-8-AQ)
complex (PS-8-AQ-Pd).
; (b) polymer anchored
Scanning electron micrographs were shown in figure 2 for PS-8-AQ ligand and the supported Pd
complex. The SEM image (b) clearly indicate the change in the morphology of polymer
supported Pd(II) catalyst C, which is due to the bonding of Pd on the surface of polystyrene
supported ligand. An energy dispersive spectroscopy analysis of X-rays (EDX) data for the
polymer anchored ligand (PS-8-AQ) (B) and (PS-8-AQ-Pd) (C) catalyst is given in Fig. 3.

The EDX data also inform that the attachment of palladium metal on the surface of the
polymer matrix. The EDX spectrum of the PS-8-AQ-Pd complex (Fig. 3) confirms the
presence of the respective atoms: C, N, Cl and Pd.
Fig. 4 TGA of polymer supported (PS-8-AQ-Pd)
C complex.
Thermal stability of the complex was investigated using thermogravimetric analysis
(TGA) at a heating rate of 10 °C min-1 over a temperature range of 30-800 °C. The TGA
curve of the polymer anchored catalyst is shown in Fig. 4. The initial negligible weight
loss up to 370 °C may be due to the removal of solvent molecules. The complex
stable up to 400 °C and above which thermal decomposition takes place.
C is
Catalytic activity
As polymer anchored metal complexes exhibit efficient catalytic activity they have been
extensively studied and reported in the field of coupling reactions. In our present work, we
investigated the catalytic activity of the PS-8-AQ–Pd catalyst to prepare benzophenones with
benzyl alcohols without using carbon monoxide. Initially, we examined the carbo-acylation of 2-
phenyl pyridine reaction with alcohols in the presence of polymer supported Pd (II) complex C
under a variety of reaction conditions. We have chosen 2-phenyl pyridine 1 and benzyl alcohol
2a as model substrates for ortho acylation (Table 1). Several oxidants such as H2O2, K2S2O8,

O2, tert-butyl hydroperoxide (TBHP), and tert-butyl peroxybenzoate (TBPB) were
screened at various temperatures as shown in Table 1. However in presence of K2S2O8,
O2, H2O2, tert-butyl peroxybenzoate (TBPB) the desired product was not obtained even at
120 °C for 24h (entries 1-3 and 5). Among the screened, tert-butyl hydroperoxide (TBHP)
proved to be the best oxidant at 110 °C for about 8h and desired product was obtained in 91
% yield in the presence of Pd complex
temperature (entry ) and low yield at 80 °C (entry
yields by increasing the reaction time from 5 to 8h at 110 °C (entry 8 and 4). However the
desired product was not obtained in absence of oxidant and Pd complex (entries 9-10).
Therefore TBHP at 110 °C in presence of Pd complex for 12h gave the desired product
C
(entry 4). But TBHP was unsuccessful at room
6
7
). There is considerable change in
C
C
3a in 91 % yield under solvent free conditions (entry 4, Table 1).
Table 1. Optimization of reaction conditionsa
b
aReaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), catalyst (15 mg), oxidant (2.0 mmol), Isolated
c
yield, No Oxidant, dNo Catalyst.

Table 2. Acylation reaction of 2-phenyl pyridine with a various benzyl alcoholsa
aReaction conditions:
oxidant (2.0 mmol),110 oC for 8 h, Isolated yield.
1 (0.5 mmol), 2a (1.0 mmol), catalyst (15 mg),
b

Table 3 Acylation reaction of 2-phenyl pyridines with aliphatic alcoholsa
Yield (%)b
trace
Alcohol
Entry
14
Product
Py
O
O
O
OH
3n
3o
3p
Py
Py
OH
72
15
78
16
OH
1 (0.5 mmol), 2
aReaction conditions: (1.0 mmol), catalyst (15 mg), oxidant (2.0 mmol),110 oC
b
for 8 h, Isolated yield.
We have extended the reaction with more challenging aliphatic alcohols for direct
aroylation of 2-phenylpyridines under the optimized reaction conditions, and the results
are represented in Table 3. It should be noted that propanol resulted in trace amount of the
desired product (Table 3, entry 14) whereas 1-octanol and 1-decanol gave the mono
acylation product with (3o) 72% and (3p) 78% yields respectively (Table 3, entries 15
and 16).
The scope of direct ortho acylation of 2-phenylpyridine with various substituted benzyl 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 8-13) and
electron withdrawing substituents at the aromatic ring (entries 2-7) proceeded to give the desired
products in good to excellent yields. However electron-donating groups substituted acylated
products (OMe, CH3) gave better yields than electron withdrawing substituents (F, Cl and
Br). The OMe substituted para
substituted meta ortho resulted in (3i) 82%, (3h) 80% yields of the desired products. In
case of methyl disubstituted, the acylated product (3j) was obtained in 84% yield.
However chloro substituted para meta ortho the desired product was achieved in (3f)
, meta, ortho gave (3k) 91%, (3l) 85%, (3m) 82% and Me
,
,
,

83%, (3e) 80%, (3d) 78% respectively. But fluoro substituted para
, meta with (3c) 82%,
(
3b) 80%, where as ortho substituted bromo gave (3g) 75% of acylated products.
Table 4 Acylation reaction of variety of N-directing groups with benzyl alcohola
aReaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), catalyst (15 mg), oxidant (2.0 mmol),
o
110 C for 8 h, bIsolated yield.

Table 5. Acylation reaction of 2-phenyl pyridine with toluene derivativesa
aReaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), catalyst (15 mg), oxidant (2.0 mmol), 110 oC
for 24 h, bIsolated yield.
In addition, we also studied the reaction with various substituted aryl pyridines, pyrazole
and pyrimidine for the directed aroylation of 2-arylpyridines under the optimized
conditions, and the results are presented in Table 4. The functional groups including Me,
OEt, OMe and naphthyl were well-suited and the desired products were achieved in
excellent yields. For example, substituted aryl pyridines with 4-methyl, ethoxy, methoxy
(which bears a strong electron-donating group) afforded the desired products 4b
, 4c, 4d,
4e, 4f in 88%, 84%, 86%, 81% and 90% respectively. In case of naphthyl substituted
pyridine the desired product 4a was obtained in 91% yield and 1-phenyl-1H-pyrazole (entry
7) gave 82% yield. As expected 2-phenylpyrimidine (entry 8) gave only diacylated product
in 78% yield due to the presence of two ortho directing nitrogen atoms. Thus the

aroylation reaction gave acylated products with variety of 2-phenyl pyridines in high
yields.
Further, we extended the scope of the reaction with toluene derivatives as acylating
partners. To our surprise both electron-donating and electron-withdrawing substituents at
the aromatic ring proceeded to give the desired products in good to excellent yields
(Table 5). However electron-donating groups substituted toluene products (OMe, CH3)
gave better yields than electron withdrawing substituents (F and Cl). The Me substituted
ortho and meta gave 75%, 70%, and OMe substituted meta
yields of the desired products. In case of chloro substituted para
was achieved in 68%, 65% and para, substituted fluoro with 70% respectively.
The recyclability of the polymer–anchored Pd (II) complex was tested in the acylation
of 2-phenyl pyridine and benzyl alcohol 2a. It was found that the catalyst can be reused
for four cycles with only 4% decline of activity after the 4th recycle as shown in Fig 5.
,
para resulted in 76%, 80%
,
meta the desired product
C
1
The AAS analytical data of used catalyst
content.
C did not show appreciable loss in the palladium
100
80
60
40
20
0
1
2
No of Cycles
3
4
Fig 5: Recyclability of Pd(II) catalyst C
Conclusion
In summary, we have developed a simple recyclable heterogeneous Pd(II) complex
C
as
versatile, active and stable catalyst for selective ortho-acylation of 2-phenyl pyridines with
benzyl alcohol and toluene derivatives as cheap acylation source. Thus this represents as an
efficient and eco-economical protocol for the carbonylation reaction as it afforded the ortho-

acylation products in excellent yields with high selectivity under solvent/carbon monoxide free
conditions with broad substrate scope.
Acknowledgements
P. S. P gratefully acknowledge to the financial assistance provided by CSIR-Senior
Research Associateship (Scientist’s Pool Scheme), New Delhi and PCP (UGC-SRF), thanks
for the fellowship provided by UGC, Govt of India. We also acknowledge director IICT for
providing infrastructural facilities.
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Graphical Abstract:
Polystyrene-supported Dichloro-(8-aminoquinoline)-Pd(II) complex C was synthesized and its
catalytic efficiency was evaluated for ortho-acylation of 2-aryl pyridines with alcohols to form
aryl ketones via cross dehydrogenative coupling. In addition in the presence of Pd (II) complex
C, toluene derivatives were also employed as an effective coupling partner for synthesis of
aromatic ketones. Furthermore, the catalyst C was highly stable and could be easily recovered by
simple filtration and reused for four cycles with no significant decrease in its activity and
selectivity.

Highlights:
Efficient Recyclable Polystyrene-supported Dichloro-(8-aminoquinoline)-Pd(II) complex
Low metal loadings with high recyclability
C-H bond acylation with benzyl alcohols as coupling partner
Broad Scope with high yields
sp2 C-H bond activation