Immobilized palladium metal containing ionic liquid catalyzed one step synthesis of isoindole-1,3-diones by carbonylative cyclization reaction

Article abstract of DOI:10.1016/j.molcata.2014.01.018

Immobilized palladium metal containing ionic liquid (ImmPd-IL) catalyzed carbonylative cyclization reaction of 2-iodobenzoic acid and primary amine provided N-substituted isoindole-1,3-dione derivatives in good to excellent yield. The influence of various reaction parameters including the effect of base, solvent, temperature, time and CO pressure on carbonylative cyclization reaction using ImmPd-IL catalyst was investigated. Using optimized reaction parameters different aromatic, aliphatic and heterocyclic N-substituted isoindole-1,3-dione derivatives were synthesized from corresponding aryl amines. The developed protocol is heterogeneous, phosphine free and requires attainable reaction conditions like atmospheric CO pressure and lesser reaction time. The scope of the developed protocol was also extended for the synthesis of N-substituted isoindole-1,3-diones from methyl-2-iodobenoate and 1,2-diiodo benzene. The ImmPd-IL catalyst was recyclable up to four consecutive cycles and recycled catalyst was characterized by XPS analysis.

Full text of DOI:10.1016/j.molcata.2014.01.018

Journal of Molecular Catalysis A: Chemical 385 (2014) 91–97
Contents lists available at ScienceDirect
Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Immobilized palladium metal containing ionic liquid catalyzed
one step synthesis of isoindole-1,3-diones by carbonylative
cyclization reaction
Mayur V. Khedkara, Ajinkya R. Shindea, Takehiko Sasakib, Bhalchandra M. Bhanagea,∗
a Department of Chemistry, Institute of Chemical Technology, N. Parekh Marg, Matunga (E), Mumbai 400 019, India
b Department of Complexity Science and Engineering, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5, Kashiwanoha, Kashiwa,
Chiba 277-8561, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Immobilized palladium metal containing ionic liquid (ImmPd-IL) catalyzed carbonylative cyclization
reaction of 2-iodobenzoic acid and primary amine provided N-substituted isoindole-1,3-dione deriva-
tives in good to excellent yield. The influence of various reaction parameters including the effect of
base, solvent, temperature, time and CO pressure on carbonylative cyclization reaction using ImmPd-IL
catalyst was investigated. Using optimized reaction parameters different aromatic, aliphatic and hetero-
cyclic N-substituted isoindole-1,3-dione derivatives were synthesized from corresponding aryl amines.
The developed protocol is heterogeneous, phosphine free and requires attainable reaction conditions
like atmospheric CO pressure and lesser reaction time. The scope of the developed protocol was also
extended for the synthesis of N-substituted isoindole-1,3-diones from methyl-2-iodobenoate and 1,2-
diiodo benzene. The ImmPd-IL catalyst was recyclable up to four consecutive cycles and recycled catalyst
was characterized by XPS analysis.
Received 26 December 2013
Received in revised form 20 January 2014
Accepted 22 January 2014
Available online 2 February 2014
Keywords:
Carbonylation reaction
Immobilization
Heterogeneous catalysis
Phosphine free
Palladium.
© 2014 Elsevier B.V. All rights reserved.
1. Introduction
and polymer industries [12]. Therefore N-substituted isoindole-
1,3-diones derivatives has become a centre of attraction to many
of the synthetic chemists.
The carbon monoxide (CO) is an important building block to
introduce carbonyl functionality into organic molecules. It is one
of the excellent C1 source and has gained considerable attention
due to its utilization for the synthesis of diverse type of carbonyl
compounds including aldehydes, ketones, esters, amides and cyclic
imides etc. [1–3]. Carbonylation methodology represents indus-
trial core technologies to convert both bulk and fine chemicals to a
diverse set of useful products of our day-to-day life.
It has been noticed that compounds possessing cyclic imide
ring system have wide spread pharmaceutical applications, as
it represents the core structural unit of various natural prod-
ucts and designed pharmaceutical molecules [4,5]. N-substituted
isoindole-1,3-diones derivatives shows medicinal applications in
the treatment of cancer [6], acquired immune deficiency syndrome
(AIDS) [7,8], leprosy [9] and other diseases [10,11]. They also find
important role in agrochemical, pharmaceutical as well as dye
The most common method for the synthesis of isoindole-
1,3-diones derivatives involves condensation of aryl amine with
phthalic anhydride [13,14]. In 1979, Ban and co-workers for the
first time developed palladium-catalysed carbonylative cyclization
method for the synthesis of isoindole-1,3-diones [15]. There-
after in 1991, Perry and Turner reported double carbonylative
cyclization of o-dihaloarenes with arylamines using PdCl2(PPh3)2
as a catalyst [16]. This work was then extended by Alper and
Cao by using phosphonium salt ionic liquid (PSIL) as a reaction
media [17]. On similar lines, Worlikar and Larock synthesized
N-substituted isoindole-1,3-diones by carbonylative cyclization
of methyl-2-iodobenzoate using homogeneous palladium com-
plex [18]. Kollar and co-workers reported the synthesis of
1,8-naphthalimides from 1,8-diiodonaphthalene, a primary amine
and CO using a palladium phosphine catalytic system [19]. Buch-
wald and co-workers developed Xantphos based catalytic system
for the aminocarbonylative cyclization reaction [20]. Rhodium(III)-
catalyzed oxidative carbonylation of benzamides was also reported
by Du et al. [21]. Begouin and Queiroz reported CO free approach
for the carbonylative synthesis of substituted isoindole-1,3-diones
[22].
∗
Corresponding author. Tel.: +91 22 3361 1111x2222; fax: +91 22 2414 5614.
E-mail addresses: bm.bhanage@gmail.com, bm.bhanage@ictmumbai.edu.in
(B.M. Bhanage).
1381-1169/$ – see front matter © 2014 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcata.2014.01.018

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M.V. Khedkar et al. / Journal of Molecular Catalysis A: Chemical 385 (2014) 91–97
Scheme 1. ImmPd-IL catalyzed carbonylative cyclization reaction.
The literature reports reveals that, carbonylative cyclization of
diiodoaryls, o-halo benzoates and o-halo benzoic acid derivatives
have been explored for the synthesis of isoindole-1,3-diones using
variety of homogeneous Pd complexes and various air and mois-
ture sensitive N/P-containing ligands. In the homogeneous catalytic
processes recovery and reuse of the palladium catalyst is a chal-
lenging task. Moreover, the used phosphine ligands are expensive,
toxic and air/moisture sensitive. In addition, requirement of high
temperature, more reaction time and high CO pressure implies con-
cerns regarding safety related issues.
The uses of immobilized palladium complexes, which are be eas-
ily recovered by simple filtration procedure, are expected to solve
this issue [23]. An ionic liquid containing palladium metal ion are
immobilized on solid support and used as catalytic precursors, thus
facilitates the reuse of catalysts [24–26]. These immobilized palla-
dium metal containing ionic liquid [ImmPd-IL] catalysts are finding
a promising use in various organic transformations [27].
Scheme 2. Preparation of palladium metal-ion-containing immobilized ionic liquid.
values were reported in Hz. Splitting patterns of proton are
described as s (singlet), d (doublet), t (triplet), and m (multiplet).
2.2. Preparation of ImmPd-IL
Immobilized metal ion-containing ionic liquid catalyst was
prepared as shown in Scheme 2. 1-Methyl-3-(3-trimethoxysilyl-
propyl) imidazolium chloride was synthesized by mixing N-
methylimidazole (0.690 mol) and 3-trimethoxysilylpropyl chloride
(0.690 mol) in a dry 300 mL flask under a nitrogen atmosphere and
refluxed for 48 h. After cooling to room temperature, the resultant
liquid was washed by dehydrated ethyl acetate five times and dried
at room temperature under reduced pressure for 48 h. The obtained
compound was stored at 253 K under dry nitrogen. Silica (Aerosil
300, surface area 300 m2/g, calcined at 573 K for 1.5 h in air) and 1-
methyl-3-(3-trimethoxysilylpropyl) imidazolium chloride (weight
ratio 1:1) was dispersed in dehydrated toluene and the mixture
was refluxed for 48 h under nitrogen. After the reflux, toluene was
removed by filtration using glass filter and the excess ionic liquid
was removed by washing with dichloromethane several times. The
resultant solid is denoted as Imm-IL.
In continuation of our ongoing research on the develop-
ment of efficient, heterogeneous and phosphine-free protocols
for carbonylative cyclization reactions [28,24], herein we report
ImmPd-IL as a common catalyst for carbonylative cyclization
reaction of 2-iodobenzoic acid, methyl-2-iodobenzoate and 1,2-
diiodobenzene with range aryl amines (Scheme 1).
2. Experimental
2.1. Materials and method
N-methylimidazole (99 + %) and 3-trimethoxysilylpropyl chlo-
ride (97 + %) were purchased from Aldrich. PdCl2 was purchased
from WAKO. Anhydrous redistilled 1-methylimidazole (99 + %) was
purchased from Aldrich. All the dehydrated solvents were obtained
from WAKO. Aerosil 300 (300 m2/g) was obtained from Japan
Aerosil Co. and calcined at 573 K for 1.5 h in air and 30 min in
vacuum before use as support. The procedure for catalyst prepa-
ration was based on our previous publication [21,22] with some
modifications. Prepared catalyst was characterized by using IR, ele-
mental analysis, and loading of the catalyst was calculated by XRF
measurements (SEA-2010, Seiko Electronic Industrial Co.). The XPS
of ImmPd-IL was measured using a PHI5000 Versa Probe with a
monochromatic focused (100 ␮m × 100 ␮m) Al K␣ X-ray radiation
(15 kV, 30 mA) and dual beam neutralization using a combination
of Argon ion gun and electron irradiation.
The products are well known in the literature and compared
with authentic samples. Progress of the reaction was moni-
tored by gas chromatography (GC). The product was purified by
column chromatography on silica gel (60–120 mesh). Gas chro-
matography analysis was carried out on Perkin Elmer Clarus 400
GC equipped flame ionization detector with a capillary column
(Elite-1, 30 m × 0.32 mm × 0.25 ␮m). GC-MS-QP 2010 instrument
(Rtx-17, 30 m × 25 mm ID, film thickness 0.25 ␮m df) (column
flow 2 mL min−1, 80–240 ◦C at 10◦/min rise.). The 1H NMR spec-
tra recorded on Varian-300 MHz FT-NMR spectrometer in CDCl3
using TMS as internal standard. The 13C NMR spectra was recorded
with JEOL FT-NMR, Model-AL300 (75 MHz) spectrometer in CDCl3.
Chemical shifts are reported in parts per million (ı) relative
to tetramethylsilane as internal standard. J (coupling constant)
In the next step, Imm-IL was added to an acetonitrile solution of
PdCl2 and refluxed for 24 h. Acetonitrile and excess of metal chlo-
ride were removed by washing acetone using glass filter several
times. The metal loading of ImmPd-IL was 3.4 wt% as determined
by XRF measurements (SEA-2010, Seiko Electronic Industrial Co.).
2.3. General procedure for carbonylative cyclization of
2-iodobenzoic acid for the synthesis of N-substituted
isoindole-1,3-diones using ImmPd-IL as a catalyst
To a 100 mL stainless steel autoclave, 2-iodobenzoic acid
(1 mmol), aryl amine (2 mmol), ImmPd-IL (2 mol%), toluene (10 mL)
and Et3N (2.5 mmol) were added. The autoclave was closed, purged
three times with nitrogen followed with carbon monoxide and
then pressurized with 1 atm of CO and heated at 100 ◦C for 4 h.
After completion of reaction the reactor was cooled to room tem-
perature, the remaining CO gas was carefully vented, and the
reactor was opened. The reactor vessel was thoroughly washed
with ethyl acetate (10–15 mL) to remove any traces of product
and catalyst if present. The catalyst was filtered and the reac-
tion mixture was evaporated under vacuum. The residue obtained
was purified by column chromatography (silica gel, 60–120 mesh;
petroleum ether/ethyl acetate, 95:05) to afford the desired prod-
uct. The products were confirmed by GC, GC-MS, 1H NMR and
13C NMR spectroscopic techniques. The purity of compounds was
determined by GC-MS analysis.

M.V. Khedkar et al. / Journal of Molecular Catalysis A: Chemical 385 (2014) 91–97
93
2.4. General experimental procedure for recycling of ImmPd-IL
After completion of the reaction, the reaction mixture was
cooled to room temperature, and the catalyst was collected by
filtration. The filtered catalyst was washed with distilled water
(3 mL × 5 mL) and methanol (3 mL × 5 mL) to remove all traces of
product or reactant present. The filtered catalyst was then dried
under reduced pressure. The dried catalyst was then used for the
further reaction.
Scheme 3. ImmPd-IL catalyzed carbonylative cyclization of methyl-2-
iodobenzoate.
2.6.7. 2-Methylisoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı 7.84 (2H, dd, J = 5.4, 3.3 Hz), 7.71
(2H, dd, J = 5.4, 3.3 Hz), 3.18 (3H, s); 13C NMR (75 MHz, CDCl3): ı
168.48, 133.89, 132.26, 123.17, 23.95.
2.5. General procedure carbonylative cyclization of
methyl-2-iodobenoate/1,2-diiodo benzene for the synthesis of
N-substituted isoindole-1,3-diones using ImmPd-IL as a catalyst
2.6.8. 2-(3-Chlorophenyl)isoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı 7.96 (2H, dd, J = 5.4, 3.3 Hz), 7.80
(2H, dd, J = 5.4, 3.3 Hz), 7.47–7.50 (1H, m), 7.39–7.41 (2H, m),
7.36–7.37 (1H, m); 13C NMR (75 MHz, CDCl3): ı 166.87, 134.67,
134.01, 132.87, 131.59, 130.08, 128.24, 126.71, 124.63, 123.95.
In a 100 mL stainless steel autoclave, methyl-2-iodobenoate/
1,2-diiodobenzene (1 mmol), aryl amine (2 mmol), ImmPd-IL
(2 mol%), toluene (10 mL) and Et3N (2.5 mmol) were added. The
autoclave was closed, purged three times with nitrogen followed
with carbon monoxide, and then pressurized with 1 atm of CO and
heated at 100 ◦C for 6 h. After completion of reaction the reac-
tor was cooled to room temperature, the remaining CO gas was
carefully vented, and the reactor was opened. The reactor vessel
was thoroughly washed with ethyl acetate (10–15 mL) to remove
any traces of product and catalyst if present. The catalyst was fil-
tered and the reaction mixture was evaporated under vacuum. The
residue obtained was purified by column chromatography (silica
gel, 60–120 mesh; petroleum ether/ethyl acetate, 95:05) to afford
the desired product. The products were confirmed by GC, GC-MS,
1H NMR and 13C NMR spectroscopic techniques. The purity of com-
pounds was determined by GC-MS analysis.
2.6.9. 2-(2-Fluorophenyl)isoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı 7.97 (2H, dd, J = 5.4, 2.7 Hz), 7.80
(2H, dd, J = 5.4, 2.7 Hz), 7.26–7.44 (4H, m); 13C NMR (75 MHz,
CDCl3): ı 166.57, 159.61, 132.0, 130.85, 130.74, 129.93, 124.72,
124.68, 123.98, 116.95.
2.6.10. 2-((5-Methylfuran-2-yl)methyl)isoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı = 7.86 (dd, 2H, J = 5.5, 3.0 Hz,), 7.71
(dd, 2H, J = 5.5, 3.0 Hz,), 6.23 (d, 1H, J = 3 Hz), 5.87 (d, 1H, J = 2.1 Hz),
4.79 (s, 2H), 2.24 (s, 3H); 13C NMR (75 MHz, CDCl3): ı = 167.5, 152,
147, 133.9, 132, 123, 109, 106, 34, 13.4.
2.6. Spectral data of the products
3. Results and discussion
2.6.1. 2-(Cyclohexylmethyl)isoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı 7.84 (2H, dd, J = 5.4, 3.3 Hz), 7.71
(2H, dd, J = 5.4, 3.3 Hz), 3.52 (2H, d, J = 6.9 Hz), 1.66–1.75 (1H, m),
1.06–1.15 (10H, m); 13C NMR (75 MHz, CDCl3): ı 168.76, 133.89,
132.09, 123.21, 44.16, 37.02, 30.78, 26.28, 25.7.
Considering the objective of the development of efficient, phos-
phine free, heterogeneous and recyclable protocol, ImmPd-IL was
developed as a common catalyst for carbonylative cyclization for
the synthesis of various aromatic, aliphatic and heterocyclic N-
substituted isoindole-1,3-diones.
2.6.2. 2-(4-(tert-butyl)benzyl)isoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı 7.83 (2H, dd, J = 5.4, 3.3 Hz), 7.69
(2H, dd, J = 5.4, 3.3 Hz), 7.31–7.39 (4H, m), 4.81 (2H, s), 1.27 (9H, s);
13C NMR (75 MHz, CDCl3): ı 168.14, 150.80, 133.98, 133.46, 132.22,
128.49, 125.64, 123.35, 41.29, 34.56, 31.34.
3.1. Immobilized Pd-IL catalyzed carbonylative cyclization of
2-iodobenzoic acid
While, setting up the protocol we observed that the nature of
solvent, base, temperature, CO pressure and reaction time needs
to be optimized for enhancing the yield of the desired products.
Hence, we optimized the reaction parameters using 2-iodobenzoic
acid with aniline as a model system in the presence of ImmPd-IL as
a catalyst (Scheme 3).
2.6.3. 2-(2-Methoxyethyl)isoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı 7.82 (2H, dd, J = 5.4, 3.3 Hz), 7.68
(2H, dd, J = 5.4, 3.3 Hz), 3.61 (2H, t, J = 5.4 Hz), 3.88 (2H, t, J = 5.4 Hz),
3.32 (3H, s); 13C NMR (75 MHz, CDCl3): ı 168.35, 133.96, 132.15,
123.30, 69.45, 58.67, 37.35.
While studying the effect of solvent we observed that, nature of
solvent plays a very crucial role in the reaction outcome. Hence var-
ious solvents like ACN, THF, DMF, DMSO and Toluene were screened
(Table 1, entries 1–5). It was observed that on decreasing the
polarity of the solvent, the yield of desired product goes on increas-
ing. This observation can be attributed to the nature of catalyst
employed for the protocol. As the ImmPd-IL catalyst is somewhat
ionic in nature, results in decrease in yield of the desired product
in polar solvents due to the interaction of catalyst with the sol-
vent, thus decreases the catalyst activity possibly due to leaching of
chloropalladate anion. Hence non-polar solvents like toluene pro-
vided promising result with the 95% yield of the desired product
(Table 1, entry 5).
2.6.4. 2-Cyclopropylisoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı = 7.88 (dd, 2H, J = 5.4, 3.3 Hz), 7.85
(dd, 2H, J = 5.4, 3.3 Hz), 2.32 (m, 1H), 0.90 (m, 4H); 13C NMR
(75 MHz): ı = 168, 134, 131, 123, 20, 5.
2.6.5. 2-Cyclopentylisoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı = 7.88 (dd, 2H, J = 5.2, 3 Hz), 7.85
(dd, 2H, J = 5.2, 3 Hz), 3.61 (m, 1H), 1.93 (m, 4H), 1.56 (m, 4H); 13
NMR (75 MHz): ı = 168, 133, 132, 122, 51, 29, 25.
C
2.6.6. 2-Neopentylisoindoline-1,3-dione
1H NMR (300 MHz, CDCl3): ı = 7.88 (dd, 2H, J = 5.4, 3.3 Hz), 7.85
(dd, 2H, J = 5.4, 3.3 Hz), 3.55 (S, 2H), 0.94 (S, 9H); 13C NMR (75 MHz):
ı = 169, 133, 132, 123, 49, 33, 28.
Considering role of base in the reaction, various organic and
inorganic bases were screened with the aim of obtaining higher
yield of expected product. The hindered amine such as DABCO,

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M.V. Khedkar et al. / Journal of Molecular Catalysis A: Chemical 385 (2014) 91–97
Table 1
Table 2
Optimization of the ImmPd-IL catalyzed carbonylative cyclization reaction of 2-
ImmPd-IL catalyzed carbonylative cyclization reaction of 2-iodobenzoic acid with
iodobenzoic acid with aniline.a
different aromatic, aliphatic and heteroaromatic amines.a
Entry
Solvent
Base
Time (h)
Temp. (◦C)
CO (atm)
Yield (%)b
Entry 2-Iodobenzoic Amine
acid
Product
Yield
(%)b
Effect of solvent
1
2
3
4
5
ACN
THF
DMF
DMSO
Toluene
Et3N
Et3N
Et3N
Et3N
Et3N
4
4
4
4
4
100
100
100
100
100
1
1
1
1
1
10
35
55
64
95
O
O
OH
N
NH2
1
90
94
I
O
Effect of base
6
7
8
Toluene
Toluene
Toluene
DABCO
DBU
K2CO3
4
4
4
100
100
100
1
1
1
70
75
35
O
O
OH
N
2
Effect of temperature
9
10
Toluene
Toluene
Et3N
Et3N
4
4
120
140
1
1
90
65
I
O
Effect of time and CO pressure
O
O
11
12
Toluene
Toluene
Et3N
Et3N
4
2
100
100
3.4
1
94
86
OH
N
3
90
91
95
Effect of catalyst loading
13c
14d
Toluene
Toluene
Et3N
Et3N
4
4
100
100
1
1
90
96
I
O
a
Reaction conditions: 2-iodobenzoic acid (1 mmol), aniline (2 mmol), ImmPd-IL
O
(2 mol%), base (2.5 mmol), solvent (10 mL).
b
GC yield.
ImmPd-IL (1.5 mol%).
ImmPd-IL (2.5 mol%).
OH
4
c
d
I
O
DBU and triethylamine were found to be compatible base (Table 1,
entries 5–7), while inorganic base (K2CO3) provided 35% yield of
the desired product (Table 1, entry 8). Thus, further reactions were
carried out using Et3N as a base (Table 1, entries 5–8).
OH
5
6
CH3–NH2
I
In order to examine the effect of temperature, reaction was
carried out at different temperatures ranging from 100 to 140 ◦C.
At 100 ◦C reaction temperature, 95% yield of 2-phenylisoindole-
1,3-dione was obtained whereas, on increasing the reaction
temperature up to 140 ◦C there was a drastic decrease in the
amountof product, whichmay be attributedto the dehalognationat
earlier stage of the reaction (Table 1, entries 9–10). Next, we studied
the effect of CO pressure, while increasing the CO pressure equiv-
alent yield of the expected product was observed hence further
reactions were carried out at 1 atm CO pressure (Table 1, entry 11).
When the reaction time was decreased, a lower yield of the desired
product was observed (Table 1, entry 12). The effect of catalyst load-
ing on the reaction outcome was also studied (Table 1, entries 5 and
13–14), Hence, the optimized reaction conditions were the follow-
ing; base, Et3N; ImmPd-IL, 2 mol%; temperature, 100 ◦C; solvent,
toluene; time, 4 h and 1 atm CO pressure.
With these optimized reaction conditions scope of the pro-
tocol was extended for the synthesis of various N-substituted
isoindole-1,3-diones by carbonylative cyclization of 2-iodobenzoic
acid with different aromatic, aliphatic and heteroaromatic aryl
amines (Table 2, entries 1–11). Model reaction of 2-iodobenzoic
acid with aniline under optimized reaction condition provided
90% isolated yield of 2-phenyl isoindole-1,3-dione (Table 2, entry
1). Reaction of different ortho, para and meta substituted aniline
derivatives including o-toluidine, p-toluidine and m-chloroaniline
provided good to excellent yield of corresponding N-substituted
isoindole-1,3-dione derivative (Table 2, entries 2–4).
O
O
OH
OH
OH
OH
N
90
O
I
O
O
O
N
7
8
89
80
81
I
O
O
I
O
O
N
9
N
I
O
O
OH
OH
10
79
82
I
It is noteworthy to mention that, the aliphatic amines
were quite eligible for the carbonylative cyclization reaction.
Aliphatic amines including methanamine, 2-methoxyethanamine
and 2,2-dimethylpropan-1-amine furnished excellent yield of the
corresponding product (Table 2, entries 5–7). Strained cyclopropyl
amine provided 80% yield of 2-cyclopropylisoindoline-1,3-dione
(Table 2, entry 8). Encouraged by these results, various heteroaro-
matic amines including 3-amine pyridine, 2-amine thiazol and
(5-methylfuran-2-yl)methanamine were screened. To our delight
O
11
I
a
Reaction conditions: 2-iodobenzoic acid (1 mmol), amine (2 mmol), Et3N
(2.5 mmol), toluene (10 mL), ImmPd-IL (2 mol%), time (4 h), CO pressure (1 atm),
temp. (100 ◦C).
b
Isolated yield.

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95
Table 3
ImmPd-IL catalyzed carbonylative cyclization reaction of methyl-2-
iodobenzoate/1,2-dihaloarenes
with
different
aromatic,
aliphatic
and
heteroaromatic amines.a
Entry Iododerivative
Amine
Product
Yield
(%)b
Scheme 4. ImmPd-IL catalyzed carbonylative cyclization of methyl-2-
iodobenzoate.
O
O
O
N
NH2
1
88
75
I
O
O
Scheme 5. ImmPd-IL catalyzed carbonylative cyclization of 1,2-diiodo benzene.
O
2
I
in all the cases good to excellent yield of corresponding N-
heterocyclic isoindole-1,3-dione was observed (Table 2, entries
9–11).
O
O
O
N
3
4
80
78
NH2
3.2. Immobilized Pd-IL catalyzed carbonylative cyclization of
methyl-2-iodobenzoate and 1,2-diiodo benzene
I
O
In order to extend the scope of the developed protocol, methyl-
2-iodobenzoate and 1,2-diiodo benzene were screened, which
provided the corresponding N-substituted isoindole-1,3-diones in
good to excellent yield (Schemes 4 and 5). Carbonylative cycliza-
tion of methyl-2-iodobenzoate was earlier reported by Larock et al.
using Pd(OAc)2 [18], and Cheng et al. by using Ni(Br2)dppe as a
catalyst [29] both of these protocols required phosphine ligand
and longer reaction time up to 24–36 h, furthermore the protocols
are homogeneous. Therefore, in order to show wide applicability
of our developed protocol, we expanded our view to synthesis of
N-substituted isoindole-1,3-diones by carbonylative cyclization of
methyl-2-iodobenzoate with primary amines using ImmPd-IL as a
catalyst (Scheme 4).
Methyl-2-iodobenzoate reacts efficiently with aniline and 2-
fluroaniline, providing 88% and 75% yield of expected product
respectively (Table 3, entries 1–2). Whereas, aliphatic amines like
cyclopropyl amine and (4-(tert-butyl)phenyl)methanamine pro-
vided 78–80% yield of expected product (Table 3, entries 3–4).
The developed catalyst was also extended for the carbonylative
cyclization of 1,2-diiodo benzene with aryl amines (Scheme 5).
Different aromatic, aliphatic and heteroaromatic aryl amines
were screened wherein the entire cases moderate to good yield
of corresponding products were obtained (Table 3 entries 5–8).
O
O
I
O
N
NH2
5
6
89
86
O
O
N
NH2
O
O
NH2
N
7
96
85
O
3.3. Recycle study
In order to prove that the developed protocol is more econom-
ical, we studied recyclability of the ImmPd-IL catalyst (Fig. 1). It
was found that the ImmPd-IL catalyst showed excellent recyclabil-
ity up to four consecutive cycles. Slight decline in the yield up to
forth recycle run was due handling loss of the catalyst after each
recycle run. To prove that our catalyst does not leaches out from
the support, we carried out hot filtration test [30], which does not
indicate any leaching of the metal in the solution.
8
a
Reaction conditions: iododerivative (methyl-2-iodobenzoate/1,2-diiodo ben-
zene) (1 mmol), amine (2 mmol), Et3N (2.5 mmol), toluene (10 mL), ImmPd-IL
(2 mol%), time (6 h), CO pressure (1 atm.), temp. (100 ◦C).
b
Isolated yield.
3.4. XPS analysis of the catalyst
species, respectively. For the 1st recycle and the 4th recycle cata-
lysts, both peaks tend to shift to lower binding energies, suggesting
that catalysts are slightly reduced during catalytic reactions. For
Cl 2p region unresolved Cl 2p3/2 and Cl 2p1/2 peaks resulted in a
broad peak at 298 eV for the fresh ImmPd-IL. For the 1st recycle and
the 4th recycle catalysts, Cl 2p peaks almost vanished. Instead, in
the I 3d region, two intensive peaks appear at 617.7 eV (I 3d5/2) and
XPS spectra were measured for the fresh ImmPd-IL, the 1st
recycle and the 4th recycle catalysts to monitor valence states of
catalysts. The wide scan and Pd 3d, Cl 2p, and I 3d regions are shown
in Fig. 2. As for Pd 3d region, two peaks appear at 337 and 342.4 eV
for the fresh ImmPd-IL, corresponding to 3d5/2 and 3d3/2 for Pd2+

96
M.V. Khedkar et al. / Journal of Molecular Catalysis A: Chemical 385 (2014) 91–97
629.2 eV (I 3d3/2) for the reused catalysts, indicating that exchange
between chlorine atoms and iodine atoms happens in the present
catalytic reactions.
4. Conclusion
In conclusion efficient heterogeneous and phosphine free proto-
col for the carbonylative cyclization reaction of 2-iodobenzoic acid
have been developed. The developed protocol found to be promis-
ing due to several aspects like requirement of less reaction time
4 h and use of atmospheric CO pressure along with wide func-
tional group tolerance affording moderate to the excellent yield
of range of N-substituted isoindole-1,3-diones. The developed cat-
alytic system was also extended for the carbonylative cyclization
of methyl-2-iodobenzoate and 1,2-diiodo benzene. Furthermore,
the catalytic system was also recycled upto four consecutive cycles
without any significant loss in catalytic activity and the recycled
catalyst was characterized by XPS analysis.
Fig. 1. Recyclability study of the ImmPd-IL catalyst.
Fig. 2. XPS analysis of the ImmPd-ILcatalyst (a, wide Scan; b, Pd3d; c, Cl2p; d, I3d).

M.V. Khedkar et al. / Journal of Molecular Catalysis A: Chemical 385 (2014) 91–97
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for Advanced Nano Characterization, the University of Tokyo, sup-
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