Carbon monoxide-free one-step synthesis of isoindole-1,3-diones by cycloaminocarbonylation of o-haloarenes using formamides

Article abstract of DOI:10.1002/ejoc.201101000

A new carbon monoxide-free, solvent-free, single step protocol for the synthesis of isoindole-1,3-diones from o-haloarenes using palladium acetate and xantphos catalysis is reported. The wider applicability of this protocol for several types of o-iodoarenes and a few o-bromoarenes makes it attractive. Aryl iodides and aryl bromides provided moderate to excellent yields of up to 93 %.

Full text of DOI:10.1002/ejoc.201101000

FULL PAPER
DOI: 10.1002/ejoc.201101000
Carbon Monoxide-Free One-Step Synthesis of Isoindole-1,3-diones by
Cycloaminocarbonylation of o-Haloarenes Using Formamides
[a]
[a]
[a]
Dinesh N. Sawant, Yogesh S. Wagh, Kushal D. Bhatte, and
Bhalchandra M. Bhanage*[
a]
Keywords: Palladium / C–H activation / Aminocarbonylation / C–C coupling
A new carbon monoxide-free, solvent-free, single step proto- types of o-iodoarenes and a few o-bromoarenes makes it at-
col for the synthesis of isoindole-1,3-diones from o-haloar- tractive. Aryl iodides and aryl bromides provided moderate
enes using palladium acetate and xantphos catalysis is re-
ported. The wider applicability of this protocol for several
to excellent yields of up to 93%.
indole-1,3-diones from o-halobenzoates, CO and amines.[11]
However, to date there has been only one report of using
o-bromobenzoic acids as a starting material for the synthe-
Introduction
Isoindole-1,3-dione derivatives, commonly known as
phthalimides, represent an important class of biologically
active compounds. Many isoindole-1,3-dione derivatives
[
12]
sis of the corresponding isoindole-1,3-diones.
cently, Chatani et al. have reported the Ru (CO) -catalyzed
More re-
[
1]
[2]
3
12
are widely used in the pharmaceutical industry. They are
usually synthesized by condensation of a phthalic anhydride
with primary amines.[ In recent years, several new method-
ologies for the synthesis of isoindole-1,3-diones using tran-
sition-metal catalysts have emerged. Generally, palladium-
catalyzed aminocarbonylation reactions are widely used for
the synthesis of acyclic amides.[4] Recent advancements in
aminocarbonylation reactions have made it possible to syn-
thesize cyclic amides such as isoindole-1,3-diones in one
step from o-halo compounds.[ Ban et al. have reported pal-
ladium-catalyzed isoindole-1,3-dione synthesis by carbon-
ylative cyclization of o-bromobenzamides, which used car-
bon monoxide as the carbonyl source.[ Similarly, Perry et
al. have reported the synthesis of isoindole-1,3-diones from
double carbonylation reactions of o-dihaloarenes with CO
and primary amines using PdCl (PPh ) catalysis in the
synthesis of isoindole-1,3-diones by carbonylative C–H
bond activation of aromatic amides, which used CO as the
carbonyl source.
3]
[
13]
All these reported protocols for the synthesis of iso-
indole-1,3-dione take place under a CO atmosphere,
whereby CO is used as the carbonyl source, which requires
relatively long reaction times. Carbon monoxide is a highly
poisonous gas, which requires specialized equipment, such as
autoclaves, and troublesome gas handling procedures. Thus,
to a certain extent the use of CO is limited in organic syn-
thesis.
5]
In recent years, there has been a rapid development of
CO-free protocols for aminocarbonylation reactions.[
Hence, in continuation of our previous work on CO-free
6]
14]
[
15]
aminocarbonylation,
we report the palladium-catalyzed,
2
3 2
CO-free synthesis of isoindole-1,3-diones from o-haloarenes
by cycloaminocarbonylation. A wide range of precursors,
presence of 1,8-diazabicyclo[5.4.0]undec-7-ene.[ Further-
more, Kollar et al. have extended a similar strategy for the
synthesis of 1,8-naphthalimides from 1,8-diiodonaphth-
7]
[
8]
alene. Recently, the protocol of Perry et al. was further
explored by Alper et al., who have used phosphonium salt
ionic liquids as reaction media.[ Larock et al. have ex-
plored the scope of o-halobenzoates for isoindole-1,3-dione
synthesis using PdCl (PPh ) catalysis with CO and
9]
2
3 2
[
10]
amine.
In addition, Buchwald et al. have also reported
the applicability of their protocol for the synthesis of iso-
[
a] Department of Chemistry, Institute of Chemical Technology,
N. Parekh Marg, Matunga, Mumbai 400019, India
Fax: +91-22-24145614
E-mail: bm.bhanage@gmail.com
bm.bhanage@ictmumbai.edu.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101000.
Scheme 1. Palladium-catalyzed, CO-free, one-step synthesis of iso-
indole-1,3-diones.
Eur. J. Org. Chem. 2011, 6719–6724
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6719

D. N. Sawant, Y. S. Wagh, K. D. Bhatte, B. M. Bhanage
FULL PAPER
such as o-dihaloarenes, o-halobenzoic acid and o-halo- various catalysts exhibited xantphos as the best ligand and
benzoate, reacted well with formamides in the presence of Pd(OAc) as the best metal precursor (Table 1, Entry 17).
2
Pd(OAc) /xantphos catalysis and provided the products in It was observed that 3 mol-% Pd(OAc) with a 1:2 metal-
2
2
a single step (Scheme 1).
to-ligand ratio was essential for a high yield of isoindole-
1,3-dione (Table 1, Entries 16–18). The use of other ligands
(Table 1, Entries 12–15) and metal precursors (Table 1, En-
tries 19–22) were futile. The formamide concentration study
showed that 5 mL of formamide per 0.5 mmol of 1,2-di-
iodobenzene was essential for high yields, and the use of a
cosolvent was ineffective (Supporting Information, S1 and
S2). The reaction temperature study showed that 140 °C
was the optimal temperature (Supporting Information, S3).
Thus, the optimized reaction conditions were: 1a
Results and Discussion
While exploring a protocol for cyanide-free cyanation,[16]
we observed that 1,2-diiodobenzene furnished isoindole-
1,3-dione as a product instead of 1,2-dicyanobenzene. In
light of this, the reaction of 1,2-diiodobenzene (1a) with
formamide (2a) in the presence of POCl was chosen as a
model reaction for the optimization of the reaction param-
eters (Table 1). The reaction was monitored at different time
intervals, and we observed that the product 3a was obtained
in 54% yield after 20 h (Table 1, Entry 4). A higher yield
was achieved with an increased concentration of POCl3
3
(0.5 mmol), POCl3 (4 mmol), Pd(OAc)2 (3 mol-%),
xantphos (6 mol-%), in 2a (5 mL) at 140 °C for 20 h.
The scope of the protocol was investigated for the reac-
tion of monosubstituted N-formamides with 1,2-diiodo-
benzene derivatives (Table 2). It was observed that 1,2-di-
iodobenzene reacted smoothly with unsubstitued, N-cyclo-
hexyl- and N-phenylformamide (Table 2, Entries 1–4),
whereas bulky formamides provided lower yields (Table 2,
Entries 5 and 6). 1,2-Diiodobenzene derivatives were also
screened, and 4,5-dimethyl-1,2-diiodobenzene provided a
high yield, whereas the reaction of 4-methyl-1,2-diiodo-
benzene resulted in a low yield of the corresponding prod-
uct (Table 2, Entries 7 and 8). It was observed that bromo-
substituted o-diarylhalides, such as 1,2-dibromobenzene
and o-bromoiodobenzene, were well-tolerated and provided
the corresponding isoindole-1,3-dione products in appreci-
able yields (Table 2, Entries 9 and 10), whereas 4,5-di-
methyl-1,2-dibromobenzene provided a moderate yield of
the expected product (Table 2, Entry 11).
(Table 1, Entry 7).
Table 1. Optimization of the CO-free synthesis of isoindole-1,3-di-
ones by reaction of 1a with 2a.[
a]
Ligand[b]
[mol-%]
Time Yield[c]
Entry Metal source
mol-%]
Lewis acid
[mmol]
[
[h]
[%]
1
2
3
4
5
6
7
8
9
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
PdCl (3)
Pd(tmhd)
NiCl (3)
Ni(OAc)
2
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(5)
(4)
(3)
(2)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L1 (10)
L2 (10)
L3 (10)
L4 (10)
L5 (10)
L1 (8)
POCl
POCl
POCl
POCl
POCl
POCl
POCl
3
3
3
3
3
3
3
(2)
(2)
(2)
(2)
(2)
(3)
(4)
(4)
(4)
(4)
48
36
24
20
18
20
20
20
20
78
64
55
54
52
66
79
15
0
2
2
The application of this protocol for other substrates was
further extended. We screened ortho-substituted derivatives
of iodobenzene, such as o-iodobenzoic acid and methyl 2-
iodobenzoate, which provided isoindole-1,3-diones. It was
observed that o-iodobenzoic acid provided highest yield
2
2
2
2
2
PCl
SOCl
FeCl
BF ·OEt
3
2
2
(Table 3). To the best of our knowledge, this is the first re-
1
0
2
3
20
0
port where o-iodobenzoic acid has been explored for the
synthesis of isoindole-1,3-dione derivatives. The use of o-
iodobenzoic acid was explored further with optimization of
the reaction parameters. It was observed that the reaction
required mild conditions and a short reaction time. Thus,
the optimized reaction conditions for o-iodobenzoic acid
1
1
2
3
2
(4) 20
20
0
1
2
2
POCl
POCl
POCl
POCl
POCl
POCl
POCl
POCl
POCl
POCl
POCl
3
3
3
3
3
3
3
3
3
3
3
(4)
60
48
0
1
3
2
(4)
(4)
(4)
(4)
(4)
(4)
(4)
(4)
(4)
(4)
20
20
1
4
2
1
5
2
20
0
1
6
2
20
20
20
20
20
20
78
77
63
74
49
0
1
7
2
L1 (6)
L1 (4)
L1 (6)
L1 (6)
L1 (6)
L1 (6)
were: 1a (1 mmol), POCl (2 mmol), Pd(OAc) (3 mol-%),
1
8
2
3
2
1
9
2
xantphos (6 mol-%), in 2 (1 mL/mmol) at 130 °C for 9 h.
Furthermore, we studied the reaction of various N-sub-
stituted formamides with o-iodobenzoic acid and observed
that all N-substituted formamides gave excellent yields of
the corresponding products. Unsubstituted, cyclic and aro-
matic formamides were well tolerated and offered excellent
yields of the desired products of up to 93% (Table 3, Entries
2
0
2
(3)
2
1
2
22
2
(3)
20
0
[
a] Reaction conditions: 1a (0.5 mmol), 2a (5 mL), Pd precursor,
ligand, Lewis acid, 140 °C, under nitrogen. [b] L1 = 4,5-bis(diphen-
ylphosphanyl)-9,9-dimethylxanthene (xantphos), L2 = 1,1-bis(di-
phenylphosphanyl)ferrocene, L3 = triphenylphosphane, L4 = tri-
butylphosphane, L5 = 1,1-bis(diphenylphosphanyl)methane. [c] GC 1–4). Bulky formamides also provided moderate yields
yield.
(Table 3, Entries 5–6).
Next, we turned our attention to o-halobenzoates and
The role of other Lewis acids was investigated, and only observed lower yields of the desired products than those
PCl was found to offer the desired product, however, at with o-halobenzoic acids. The optimized reaction condi-
3
lower yields than POCl (Table 1, Entries 7–11). Screening tions for o-iodobenzoates were: 5a (1 mmol), POCl3
3
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6719–6724

CO-Free One-Step Synthesis of Isoindole-1,3-diones
Table 2. CO-free synthesis of isoindole-1,3-diones by reaction of o-
diihalobenzenes (1) with formamides (2).[
Table 3. CO-free synthesis of isoindole-1,3-diones by reaction of o-
halobenzoic acid with formamides.
a]
[a]
[
(
a] Reaction conditions: 4a (1 mmol), 2 (1 mL/mmol), Pd(OAc)
3 mol-%), xantphos (6 mol-%), POCl (2 mmol), 130 °C, 9 h. [b]
Isolated yield.
2
3
(
(
2 mmol), Pd(OAc) (3 mol-%), xantphos (6 mol-%), in 2
4 mL/mmol) at 140 °C for 20 h. The effect of various N-
2
substituted formamides with methyl 2-iodobenzoate was
also investigated. It was observed that all N-substituted for-
mamides furnished moderate yields of the corresponding
products (Table 4, Entries 1–4), whereas sterically hindered
formamide derivatives provided lower yields (Table 4, En-
tries 5 and 6). It is worth mentioning that no N-arylated
product was observed in any reaction of formamides with
o-aryl halides.
The applicability of our protocol was investigated for the
synthesis of other biologically important heterocycles by re-
action of o-iodobenzyl alcohol (6) with formamide under
the reaction conditions for o-halobenzoates. Isobenzofuran-
1
(3H)-one (7) was obtained in appreciable yield (up to 70%,
[
%
a] Reaction conditions: 1 (0.5 mmol), 2 (5 mL), Pd(OAc)
), xantphos (6 mol-%), POCl (4 mmol), 140 °C, 20 h. [b] Isolated
yield. [c] Reaction conditions: 1 (0.5 mmol), 2 (5 mL/mmol),
2
(3 mol-
Scheme 2). This observation and our other results suggest
that by varying the ortho substituent on o-halobenzene vari-
3
Pd(OAc)
mamide (5 mL), 160 °C, 24 h.
2
(5 mol-%), xantphos (10 mol-%), POCl
3
(4 mmol), for- ous heterocycles can be synthesized, highlighting the wide
applicability of this protocol.
Eur. J. Org. Chem. 2011, 6719–6724
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6721

D. N. Sawant, Y. S. Wagh, K. D. Bhatte, B. M. Bhanage
FULL PAPER
Table 4. CO-free synthesis of isoindole-1,3-diones by reaction of o- o-halobenzoates 4B is the intermediate. These intermediates
halobenzoate with formamides.[
a]
offer the aminocarbonylated products 5A and 5B. In the
case of 5A, the amide lone pair attacks the carbonyl group
of the second o-amide and undergoes intramolecuclar cycli-
zation, which provides isoindole-1,3-dione 6. In case of 5B,
the amide lone pair attacks the acid/ester carbonyl group
and undergoes intramolecular cyclization to give 6.
[
(
a] Reaction conditions: 5a (1 mmol), 2 (4 mL/mmol), Pd(OAc)
5 mol-%), xantphos (10 mol-%), POCl (2 mmol), 140 °C, 20 h. [b]
Isolated yield.
2
3
Scheme 3. Proposed mechanism for CO-free synthesis of isoindole-
,3-diones.
1
Scheme 2. Application of the CO-free protocol for the synthesis of
heterocycles: preparation of 7.
Conclusions
We report a new, simple, CO-free protocol for the synthe-
sis of isoindole-1,3-diones. For the first time, the scope of
Mechanism
From our previous studies on CO-free aminocarbon- o-halo acids has been explored for such a synthesis. The
[
15]
[16]
ylation, cyanide-free cyanation and the present results, wide applicability of the protocol for several types of o-
we predict that CO-free synthesis of isoindole-1,3-diones in- iodoarenes and some o-bromoarenes makes it attractive.
volves oxidative insertion of Pd into the C–X bond, which The new protocol is a single step, wherein additional sol-
gives an aryl palladium halide intermediate 1 (Scheme 3). vent is not required as formamide plays the dual role of
Thereafter, imminium salt 2 (Vilsmeier-type reagent) un- solvent and substrate. This methodology can also be ap-
dergoes nucleophilic addition of the aryl palladium halide plied to the synthesis of other important heterocycles such
to form 3. In the case of o-dihaloarenes, this process is com- as isobenzofuran-1(3H)-one. Our protocol might prove to
mon for both the o-halo groups. Intermediate 3 then un- be a promising alternative to conventional methodologies
dergoes β-hydride elimination to form 4, which is a key in- for the synthesis of isoindole-1,3-diones and other heterocy-
termediate in the reaction. In the case of o-dihaloarenes 4A cles. Further application of the protocol and studies on the
is the intermediate, whereas in the case of o-halo acids and CO-free synthesis of heterocycles are underway.
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6719–6724

CO-Free One-Step Synthesis of Isoindole-1,3-diones
column chromatography on silica gel (petroleum ether/ethyl acet-
ate) to afford the pure product.
Experimental Section
Materials and Methods: All chemicals were purchased from Sigma
Aldrich, Lancaster (Alfa-Aesar), S. D. Fine Chemicals and other
commercial suppliers. All reactions were carried out under a nitro-
gen atmosphere. The progress of the reaction was monitored by
TLC using Merck silica gel 60 F254 plates. The products were visu-
alized with a 254 nm UV lamp. The products were purified by col-
umn chromatography on silica gel (60–120) mesh. All yields re-
4. Typical Procedure for the Synthesis of Isoindole-1,3-dione from
Methyl o-Iodobenzoate: In a 25 mL two-necked round-bottomed
flask equipped with a condenser, a mixture of methyl o-iodobenzo-
2
ate (1 mmol), Pd(OAc) (5 mol-%), Xantphos (10 mol-%) and
POCl (2 mmol) in formamide (4 mL/mmol) under nitrogen was
3
stirred at 140 °C for 20 h. After completion, the reaction mixture
was cooled to room temperature and poured into a saturated solu-
ported in Tables 2, 3 and 4 refer to isolated yields and purity as
determined by 1H and 13C NMR spectroscopy and GC–MS,
tion of NaHCO
acetate (4ϫ20 mL). The combined organic layers were dried with
Na SO and evaporated to afford the crude product, which was
3
(50 mL). The product was extracted into ethyl
whereas yields reported in Table 1 are GC yields. All products are
1
2
4
known compounds and were identified by techniques such as H
1
3
purified by column chromatography on silica gel (petroleum ether/
ethyl acetate combination) to afford the pure product. The product
and C NMR and FTIR spectroscopy and GC–MS and were com-
1
13
pared with previously reported data. H and C NMR spectra
were recorded with a JEOL FT NMR, Model-AL300 (300 MHz)
spectrometer in CDCl . Chemical shifts (δ) are reported in parts
3
per million (ppm) relative to tetramethylsilane as internal standard.
Coupling constants (J) are reported in Hertz (Hz). Splitting pat-
terns are described as s (singlet), d (doublet), t (triplet), m (mul-
1
13
was confirmed by GC–MS and H and C NMR spectroscopic
analysis.
1
Isoindole-1,3-dione (3a): H NMR (300 MHz, CDCl , 25 °C): δ =
3
1
3
7.81 (s, 4 H), 11.33 (br. s, 1 H) ppm. C NMR (75 MHz, CDCl3,
25 °C): δ = 169.2, 134.2, 132.6, 122.9 ppm. GC–MS (EI, 70 eV):
+
tiplet). Mass spectra were obtained with a Shimadzu GC-MS-QP m/z (%) = 147 (100) [M] , 104 (58), 76 (54), 50 (21).
2
010 instrument. IR spectra were recorded with an FTIR spec-
1
2
2
1
3
-Cyclohexylisoindole-1,3-dione (3b): H NMR (300 MHz, CDCl ,
trometer (Perkin–Elmer). GC analysis was carried out with a
Perkin–Elmer (Clarus-400) gas chromatograph equipped with
5 °C): δ = 1.25–1.44 (m, 3 H), 1.74–1.71 (m, 3 H), 1.87 (d, J =
2.46 Hz, 2 H), 2.22–2.18 (m, 2 H), 4.16–4.05 (m, 1 H), 7.69 (dd,
J = 5.5, 3.3 Hz, 2 H), 7.81 (dd, J = 5.5, 3.0 Hz, 2 H) ppm.
flame ionization detector and
0 mϫ0.32 mmϫ0.25 μm).
a capillary column (Elite-1,
1
3
C
3
NMR (75 MHz, CDCl
3
, 25 °C): δ = 168.52, 133.80, 132.10, 123.05,
General Experimental Procedure
. Typical Procedure for the Synthesis of Isoindole-1,3-diones from
o-Diiodoarenes: A mixture of o-diiodoarene (0.5 mmol), Pd(OAc)
3 mol-%) and xantphos (6 mol-%) in formamide (5 mL) was
placed in a 25 mL two-necked round-bottomed flask equipped with
a condenser under nitrogen at room temperature. POCl (4 mmol)
50.90, 29.91, 26.06, 25.1 ppm. GC–MS (EI, 70 eV): m/z (%) = 229
+
(
36) [M] , 186 (34), 148 (100), 160 (10), 130 (41), 104 (14), 76 (17).
1
IR (Neat): ν˜ = 3454, 2928, 2855, 1761, 1708, 1613, 1376, 1169,
2
–
1
1
086, 1018, 903, 714 cm .
2-Phenylisoindole-1,3-dione (3c): 1H NMR (300 MHz, CDCl
25 °C): δ = 7.38–7.53 (m, 5 H), 7.79 (dd, J = 5.4, 1.5 Hz, 2 H), 7.96
(
3
,
3
1
3
was added, and the reaction mixture was stirred at 140 °C for 20 h.
After completion, the reaction mixture was cooled to room tem-
3
(dd, J = 5.5, 3.3 Hz, 2 H) ppm. C NMR (75 MHz, CDCl , 25 °C):
δ = 167.26, 134.39, 131.72, 131.65, 129.10, 128.09, 126.57,
+
perature and poured into a saturated solution of NaHCO
The product was extracted into diethyl ether (4ϫ20 mL). The com-
bined organic layers were dried with Na SO and evaporated to
3
(50 mL).
123.72 ppm. GC–MS (EI, 70 eV): m/z (%) = 223 (100) [M] , 179
(70), 104 (20), 76 (41), 50 (13). IR (Neat): ν˜ = 3076, 1709, 1595,
–
1
1496, 1388, 1117, 881, 761, 718 cm .
2
4
afford the crude product, which was purified by column
chromatography on silica gel (petroleum ether/ethyl acetate) to af-
ford the pure product.
-p-Tolylisoindole-1,3-dione (3d): 1H NMR (300 MHz, CDCl
2
2
2
3
,
5 °C): δ = 2.40 (s, 3 H), 7.31 (m, 4 H), 7.78 (dd, J = 5.5, 2.9 Hz,
13
H), 7.94 (dd, J = 5.2, 2.9 Hz, 2 H) ppm. C NMR (75 MHz,
CDCl
3
, 25 °C): δ = 167.44, 138.18, 134.34, 131.81, 129.80, 128.98,
2
. Typical Procedure for the Synthesis of Isoindole-1,3-diones from
o-Dibromoarenes: In a 25 mL two-necked round-bottomed flask
equipped with condenser, mixture of o-dibromoarene
0.5 mmol), Pd(OAc) (5 mol-%), xantphos (10 mol-%) and POCl
4 mmol) in formamide (5 mL) under nitrogen was stirred at 160 °C
126.48, 123.69, 29.71 ppm. GC–MS (EI, 70 eV): m/z (%) = 238
+
(
100) [M] , 193 (50), 104 (20), 76 (41). IR (Neat): ν˜ = 2923, 1717,
a
a
–
1
1610, 1516, 1385, 1221, 1098, 819, 724 cm .
(
(
2
3
-o-Tolylisoindole-1,3-dione (3e): 1H NMR (300 MHz, CDCl
2
3
,
for 24 h. After completion, the reaction mixture was cooled to
room temperature and poured into a saturated solution of
NaHCO
25 °C): δ = 2.21 (s, 3 H), 7.2 (d, J = 7.3 Hz, 1 H), 7.38–7.53 (m, 3
H), 7.80 (dd, J = 5 Hz, 2 H), 7.96 (dd, J = 5.5, 2.9 Hz, 2 H) ppm.
3
(50 mL). The product was extracted into ethyl acetate
SO
4
13
C NMR (75 MHz, CDCl
3
, 25 °C): δ = 167.36, 136.56, 134.35,
(4ϫ20 mL). The combined organic layers were dried with Na
2
132.01, 131.16, 130.61, 129.46, 128.74, 126.89, 123.77, 18.05 ppm.
and evaporated to afford the crude product, which was purified by
column chromatography on silica gel (petroleum ether/ethyl acet-
ate) to afford the pure product.
+
GC–MS (EI, 70 eV): m/z (%) = 238 (100) [M] , 191 (23), 104 (20),
76 (45). IR (Neat): ν˜ = 3088, 1723, 1620, 1497, 1463, 1381, 1226,
–1
1112, 885, 771, 719 cm .
3
. Typical Procedure for the Synthesis of Isoindole-1,3-diones from 2-(Naphthalen-2-yl)isoindole-1,3-dione (3f):
1
H NMR (300 MHz,
CDCl , 25 °C): δ = 7.54 (m, 3 H), 7.99–7.87 (m, 8 H) ppm. 13
o-Iodobenzoic Acid: In a 25 mL two-necked round-bottomed flask
equipped with a condenser, a mixture of o-iodobenzoic acid
C
3
NMR (75 MHz, CDCl , 25 °C): δ = 167.53, 134.53, 133.35, 132.68,
3
(1 mmol), Pd(OAc)
2
(3 mol-%), xantphos (6 mol-%) and POCl
3
131.88, 129.06, 128.29, 127.83, 126.78, 125.58, 124.25, 123.86 ppm.
(
2 mmol) in formamide (1 mL/mmol) under nitrogen was stirred at IR (Neat): ν = 3027, 1710, 1596, 1470, 1380, 1083, 831, 716 cm–1
.
˜
130 °C for 9 h. After completion, the reaction mixture was cooled
5
(
,6-Dimethylisoindoline-1,3-dione (3g): GC–MS (EI, 70 eV): m/z
%) = 175 (100) [M] , 132 (65), 104 (54), 77 (18), 51 (20).
to room temperature and poured into a saturated solution of
NaHCO (50 mL). The product was extracted into ethyl acetate
4ϫ20 mL). The combined organic layers were dried with Na SO
and evaporated to afford the crude product, which was purified by
+
3
(
2
4
5-Methylisoindoline-1,3-dione (3h): GC–MS (EI, 70 eV): m/z (%) =
161 (100) [M] , 118 (69), 90 (54), 63 (20), 51 (7).
+
Eur. J. Org. Chem. 2011, 6719–6724
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6723

D. N. Sawant, Y. S. Wagh, K. D. Bhatte, B. M. Bhanage
FULL PAPER
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Published Online: September 19, 2011
6724
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Eur. J. Org. Chem. 2011, 6719–6724