Carbonylative synthesis of phthalimides and benzoxazinones by using phenyl formate as a carbon monoxide source

Article abstract of DOI:10.1002/ejoc.201500109

A simple and efficient palladium-catalyzed carbonylative cyclization of N-substituted 2-iodobenzamides and 2-iodoanilides was investigated for the synthesis of phthalimides and benzoxazinones, respectively, by using phenyl formate as a CO source. The present catalytic protocol circumvents the use of an expensive phosphine ligand as well as solvent in the case of the phthalimide synthesis. Moreover, mild reaction conditions and a tolerance of various functional groups enhance the general applicability of this method.

Full text of DOI:10.1002/ejoc.201500109

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FULL PAPER
DOI: 10.1002/ejoc.201500109
Carbonylative Synthesis of Phthalimides and Benzoxazinones by Using Phenyl
Formate as a Carbon Monoxide Source
Sujit P. Chavan[a] and Bhalchandra M. Bhanage*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Carbonylation / Cyclization / Palladium
A simple and efficient palladium-catalyzed carbonylative cy- use of an expensive phosphine ligand as well as solvent in
clization of N-substituted 2-iodobenzamides and 2-iodoanil- the case of the phthalimide synthesis. Moreover, mild reac-
ides was investigated for the synthesis of phthalimides and
benzoxazinones, respectively, by using phenyl formate as a
CO source. The present catalytic protocol circumvents the
tion conditions and a tolerance of various functional groups
enhance the general applicability of this method.
to generate CO.[10] Recently, two groups independently re-
ported the use of aryl formate as a CO source for the esteri-
fication of aryl halides.[11] Yasushi Tsuji and co-workers re-
ported the hydroesterification of alkynes and alkenes by
using aryl formate as the CO source.[12] Later, Yian Shi and
co-workers synthesized a variety of lactones by employing
the hydroesterification of alkenylphenols using phenyl for-
mate as the CO source.[13] Very recently, Beller and co-
workers reported the use of aryl formate as a bifunctional
reagent, that is, a pseudohalide, as well as a CO source for
various carbonylation reactions.[14]
In continuation with our ongoing research of simple, less
toxic, atom efficient and carbon monoxide free protocols
for carbonylation reactions,[15] we herein report the synthe-
sis of N-substituted phthalimides and benzoxazinones by
using phenyl formate as a simple and efficient carbon mon-
oxide source. Moreover, the methodology has also been suc-
Introduction
Annulated heterocycles such as phthalimides and benzo-
xazinones are important motifs that are present in the nu-
merous biologically active molecules.[1] Hence, the develop-
ment of environmentally benign protocols for the synthesis
of annulated heterocycles has always been a key area of
interest among organic chemists. The classical approach to
synthesize phthalimides involves the condensation of a
phthalic anhydride with a primary amine.[2] Benzoxazi-
nones are typically synthesized by the cyclization of anthra-
nilic acids, N-acylanthranilic acids, or isatonic anhydrides.[3]
In recent years, transition-metal-catalyzed direct carb-
onylation reactions have served as a prime method for the
synthesis of various heterocycles by using carbon monoxide
gas as C1 source.[4] In this regard, there are only few reports
of transition-metal-catalyzed carbonylative syntheses of
phthalimides[5] and benzoxazinones,[6] which use CO gas as
a C1 source. Indeed, CO gas is most widely used as a C1
source, but it is highly lethal, and there are concerns involv-
ing its handling, storage, transport, and need for a specially
designed high-pressure reactor, which restricts its common
use among academic researchers. Hence, the development
of new methodology that involves the use of simple, easy-
to-handle, and less toxic CO surrogates is highly desirable.[7]
In recent years, much development has been made in this
direction, and various inorganic[8] and organic[9] carbon
monoxide alternatives have been intensively examined.
Ilhyong Ryu and co-workers developed a two chamber tech-
nique and continuous microflow tube-in-tube reactor sys-
tem for an aminocarbonylation by using a Morgan reaction
[a] Department of Chemistry, Institute of Chemical Technology,
N. Parekh Marg, Matunga, Mumbai 400019, India
E-mail: bm.bhanage@gmail.com
bm.bhanage@ictmumbai.edu.in
http://www.ictmumbai.edu.in/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500109.
Scheme 1. Carbon monoxide free synthesis of phthalimide and
benzoxazinone.
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cessfully applied to the synthesis of amino acid derived and electron-withdrawing groups such as the nitro group
phthalimides (Scheme 1).
were also well-tolerated to provide the corresponding prod-
ucts 3b–3f in excellent yields. N-benzyl and N-benzyl groups
with either a cyano or tert-butyl substituent were also sus-
tainable under the optimized reaction conditions (i.e., 3g–
3i). Various simple aliphatic as well as cyclic N-substituted
2-iodobenzamides also worked well and furnished the cor-
responding phthalimides 3j–3o in good yields. Moreover, 2-
iodobenzamides with an N-heterocyclic substituent such as
a pyridine, substituted pyridine, thiazole, or quinolone
group were also compatible under the present catalytic sys-
tem (i.e., 3p–3s). Chiral N-substituted 2-iodobenzamides
were also successful under the present reaction conditions
to furnish the corresponding phthalimides 3t and 3u in
good yields.
Results and Discussion
We started our initial investigation by employing 2-iodo-
N-phenylbenzamide (1a) as a model substrate, phenyl for-
mate (2) as a CO source, and NEt3 as a base in the presence
of a palladium catalyst at 80 °C (Table 1). We then screened
different bidentate nitrogen ligands such as 1,10-phen-
anthroline, 2,2Ј-bipyridine, and bathophenanthroline
(Table 1, Entries 2–4) and found that 2,2Ј-bipyridine pro-
vided N-phenylphthalimide (3a) in 60% yield (Table 1, En-
try 2). A significant improvement in the yield of 3a was ob-
served by switching from an aromatic to an aliphatic biden-
tate ligand (Table 1, Entry 5). Subsequently, we screened
various palladium catalysts (Table 1, Entries 6–9). Among
them, PdCl2(PhCN)2 gave 3a in 93% yield (Table 1, En-
try 7), However, the reaction did not proceed in the absence
of the catalyst (Table 1, Entry 10). We also studied the effect
of various solvents and determined that polar solvents are
more effective for this transformation (Table 1, Entries 11–
13). Surprisingly, the reaction also worked very well under
solvent-free conditions, which furnished 3a in 92% yield
(Table 1, Entry 14).
Table 2. Substrate scope for phthalimide synthesis.[a]
Table 1. Optimization of the reaction conditions.[a]
Entry Catalyst
Ligand
Solvent Yield [%][b]
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2(PPh3)2 TMEDA
PdCl2(PhCN)2 TMEDA
–
DMF[c]
DMF
DMF
10
60
38
45
88
70
93
69
70
00
64
45
81
92
2,2Ј-bipyridine
1,10-phenanthroline
bathophenanthroline DMF
TMEDA[c]
DMF
DMF
DMF
DMF
DMF
DMF
THF[c]
toluene
ACN[c]
–
Pd(PPh3)4
TMEDA
TMEDA
TMEDA
[c]
9
Pd(dba)2
10
11
12
13
14[d]
–
PdCl2(PhCN)2 TMEDA
PdCl2(PhCN)2 TMEDA
PdCl2(PhCN)2 TMEDA
PdCl2(PhCN)2 TMEDA
[a] Reagents and conditions: 1a (0.5 mmol), 2 (1 mmol), catalyst
(4 mol-%), ligand (8 mol-%), and NEt3 (1 mmol) in solvent (1 mL).
The reaction mixture was stirred at 80 °C for 18 h. [b] GC yields.
[c] dba = dibenzylideneacetone, TMEDA = N,N,NЈ,NЈ-tetramethyl-
1,2-ethylenediamine, DMF = N,N-dimethylformamide, THF =
tetrahydrofuran, ACN = acetonitrile. [d] NEt3 (2 mmol) was used.
To evaluate the scope and limitations of the developed
protocol, we applied the optimized reaction parameters to
various N-substituted 2-iodobenzamides, which were con-
verted into the corresponding phthalimides in good to ex-
cellent yields (Table 2). Notably, various substituents on the
N-phenyl ring, which include halo groups such as –F and
[a] Reagents and conditions: 1a–1u (0.5 mmol), 2 (1 mmol), catalyst
(4 mol-%), ligand (8 mol-%), and NEt3 (2 mmol). The reaction
mixture was then stirred at 80 °C for 18 h. [b] DMF (1 mL) was
used as the solvent.
To our delight, chiral amino acid derived 2-iodobenzam-
–Cl, electron-donating groups such as –CH3 and –OMe, ides were tested under the optimized reaction conditions,
2
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Carbonylative Synthesis of Phthalimides and Benzoxazinones
and the corresponding phthalimides 5a and 5b were ob- into the corresponding benzoxazinones in good to excellent
tained in good yields (Scheme 2).
yields (Table 4). Various substituted aryl rings such as those
with an electron-donating or electron-withdrawing group
(7b–7e), a halo group (7f–7i), and a benzyl or substituted
benzyl group (7j and 7k) as well as a functionalized alkyl
group (7l) were introduced at the second position of the
benzoxazinone. Compound 7m, which has antifungal and
antibacterial activity, was also prepared in high yield under
the optimized reaction conditions.[16] When we submitted
the 2-iodoanilide with a m-chloro substituent to the reac-
tion, the corresponding benzoxazinone 7n was furnished in
75% yield.
Scheme 2. Amino acid derived chiral phthalimide synthesis.
Our success with the carbonylative cyclization of N-sub-
stituted 2-iodobenzamides inspired us to investigate the cy-
clization of 2-iodoanilides. Initially, the optimized param-
eters for the phthalimide synthesis were applied to the prep-
aration of a benzoxazinone. However, compound 7a was
formed in poor yield under these conditions (Table 3, En-
try 1). We then screened various bidentate nitrogen ligands
in toluene as the solvent to increase the yield of 7a, but the
yield of the desired product was still very poor (Table 3,
Entries 2–5). Consequently, we changed the ligand and ex-
amined various phosphine ligands (Table 3, Entries 6–11).
Among them, Xantphos [4,5-bis(diphenylphosphino)-9,9-
dimethylxanthene] served as the best ligand and gave com-
pound 7a in 90% yield (Table 3, Entry 11). Next, the effect
of the palladium catalyst was examined (Table 3, En-
tries 11–13), and we found that PdCl2(PhCN)2 provided an
excellent yield of 7a (Table 3, Entry 11).
Table 4. Substrate scope for benzoxazinone synthesis.[a]
Table 3. Optimization of the reaction conditions for benzoxazinone
synthesis.[a]
Entry Catalyst
Ligand
Yield [%][b]
1[c]
2
3
PdCl2(PhCN)2
TMEDA
TMEDA
Ͻ10
Ͻ10
Ͻ10
Ͻ10
Ͻ10
58
65
65
87
68
[a] Reagents and conditions: 6a–6n (0.5 mmol), 2 (1 mmol), catalyst
(4 mol-%), ligand (8 mol-%), and NEt3 (1 mmol) in solvent (1 mL).
The reaction mixture was stirred at 80 °C for 18 h.
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
Pd(OAc)2
2,2Ј-bipyridine
1,10-phenanthroline
bathophenanthroline
PPh3
4
5
6[d]
7
On the basis of previous reports, we have proposed a
plausible reaction mechanism for the phthalimide synthesis
(Scheme 3). Initially, the in situ generated Pd0 species[17]
underwent an oxidative addition to 2-iodobenzamide to
give arylpalladium intermediate I. Next, the arylpalladium
species I is converted into acylpalladium species II in the
presence of CO that is generated from the decomposition
of phenyl formate.[11] The conversion of acylpalladium spe-
cies II into product 3a may occur through two pathways.
Path A proceeds through a phenoxycarbonylation of acyl-
palladium species II,[11c] which undergoes an intramolecular
cyclization to form 3a, whereas path B proceeds through an
dppf[e]
8
dppp[e]
9[d]
10
11
12
13
P(tBu)3·HBF4
dppb[e]
Xantphos
Xantphos
Xantphos
90
86
80
Pd(dba)2
[a] Reagents and conditions: 6a (0.5 mmol), 2 (1 mmol), catalyst
(4 mol-%), ligand (8 mol-%), and NEt3 (1 mmol) in toluene (1 mL)
at 80 °C for 18 h. [b] GC yield. [c] Without solvent in the presence
of NEt3 (2 mmol). [d] Ligand (16 mol-%) was used. [e] dppf = 1,1Ј-
bis(diphenylphosphino)ferrocene, dppp = 1,3-bis(diphenylphos-
phino)propane, dppb = 1,4-bis(diphenylphosphino)butane.
With these optimized reaction parameters, we were ple- intramolecular attack of the nucleophile on acylpalladium
ased to find that various 2-iodoanilides could be converted species II to form 3a.
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ated, backfilled with nitrogen, and charged with PdCl2(PhCN)2
(7.6 mg, 0.02 mmol), TMEDA (4.64 mg, 0.04 mmol), the 2-iodob-
enzamide (0.5 mmol), phenyl formate (122.12 mg, 1 mmol), and tri-
ethylamine (202.38 mg, 2 mmol) under nitrogen. The reaction mix-
ture was stirred at 80 °C for 18 h and then was diluted with EtOAc.
The resulting mixture was washed with aqueous NaHCO3 (2ϫ
10 mL). The combined aqueous phases were extracted with ethyl
acetate (3ϫ 10 mL), and the combined organic layers were washed
with brine and dried with Na2SO4. The solvent was removed under
reduced pressure to give the crude residue, which was purified by
column chromatography on silica gel (ethyl acetate/petroleum
ether) to give the corresponding phthalimide.
General Procedure for the Synthesis Benzoxazinones from 2-Iodoani-
lides and Phenyl Formate: An oven-dried Schlenk tube was evacu-
ated, backfilled with nitrogen, and charged with PdCl2(PhCN)2
(7.6 mg, 0.02 mmol), Xanthphos (23.14 mg, 0.04 mmol), the 2-
iodoanilide (0.5 mmol), phenyl formate (1 mmol), and triethyl-
amine (1 mmol) in toluene (1 mL) under nitrogen. The reaction
mixture was stirred at 80 °C for 18 h and then was diluted with
EtOAc. The resulting mixture was washed with aqueous NaHCO3
(2ϫ 10 mL). The combined aqueous phases were extracted with
ethyl acetate (3ϫ 10 mL), and the combined organic layers were
washed with brine and dried with Na2SO4. The solvent was re-
moved under reduced pressure to give the crude residue, which was
purified by column chromatography on silica gel (ethyl acetate/pe-
troleum ether) to give the corresponding benzoxazinone.
Scheme 3. Plausible reaction mechanism for the phthalimide syn-
thesis.
Characterization of Selected Compounds
Conclusions
2-(2-Fluorophenyl)isoindoline-1,3-dione
(3b):[5e]
White
solid
In summary, the present protocol provides the highly ef-
ficient PdCl2(PhCN)2-catalyzed carbonylative cyclization of
2-iodobenzamides and 2-iodoanilides by using phenyl for-
mate as a CO source to furnish the corresponding phthal-
imides and benzoxazinones, respectively. The protocol is
phosphine- and solvent-free for the synthesis of various
phthalimide derivatives. Moreover, for the first time, the
process was successfully applied to the carbonylative cycli-
zation of amino acid derived N-substituted 2-iodobenzam-
ides.
1
(102 mg, 85% yield). H NMR (400 MHz, CDCl3): δ = 7.97 (dd, J
= 5.2, 3.2 Hz, 2 H), 7.81 (dd, J = 5.2, 3.2 Hz, 2 H), 7.48–7.43 (m,
1 H), 7.37 (t, J = 6.8 Hz, 1 H), 7.31–7.25 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 166.5, 159.1, 131.9, 130.8, 130.7, 129.8,
124.6, 124.6, 123.9, 116.6 ppm.
2-(3-Chlorophenyl)isoindoline-1,3-dione
(3c):[5e]
White
solid
1
(115 mg, 90% yield). H NMR (400 MHz, CDCl3): δ = 7.96 (dd, J
= 5.2, 3.2 Hz, 2 H), 7.81 (dd, J = 5.2, 3.2 Hz, 2 H), 7.50–7.37 (m,
4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 166.8, 134.6, 132.8,
131.5, 130.0, 128.2, 126.6, 124.5, 123.9, 123.7 ppm.
2-[4-(tert-Butyl)benzyl]isoindoline-1,3-dione (3i):[5e] White solid
1
(118 mg, 81% yield). H NMR (400 MHz, CDCl3): δ = 7.80 (dd, J
Experimental Section
= 5.2, 3.2 Hz, 2 H), 7.64 (dd, J = 5.2, 3.2 Hz, 2 H), 7.38 (d, J =
8.4 Hz, 2 H), 7.32 (d, J = 8.4 Hz, 2 H), 4.81 (s, 2 H), 1.27 (s, 9
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 167.9, 150.6, 134.1,
133.8, 133.4, 128.4, 125.5, 123.2, 41.1, 34.4, 31.2 ppm.
General Methods: All reactions were performed in oven-dried glass-
ware under nitrogen. The progress of the reactions were monitored
by TLC on Merck silica gel 60 F254 plates, and the developed
plates were visualized by UV light at 254 nm. The products were
purified by column chromatography on silica gel (120–200 mesh).
All yields that are reported in Tables 2 and 4 as well as in Scheme 2
refer to isolated yields, and the yields that are reported in Tables 1
and 3 are GC yields. The 1H and 13C NMR spectroscopic data
were recorded with a Bruker-400 MHz spectrometer, and tet-
ramethylsilane was used as the internal standard in CDCl3. Chemi-
2-Methylisoindoline-1,3-dione (3j):[5e] White solid (70 mg, 87%
1
yield). H NMR (400 MHz, CDCl3): δ = 7.84 (dd, J = 5.2, 3.2 Hz,
2 H), 7.71 (dd, J = 5.2, 3.2 Hz, 2 H), 3.18 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.4, 133.8, 132.2, 123.1, 23.9 ppm.
2-(2-Methoxyethyl)isoindoline-1,3-dione (3l):[5e] White solid (73 mg,
1
72% yield). H NMR (400 MHz, CDCl3): δ = 7.85–7.83 (m, 2 H),
7.73–7.71 (m, 2 H), 3.90 (t, J = 5.6 Hz, 2 H), 3.64 (t, J = 5.6 Hz,
2 H), 3.35 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.2,
133.6, 132.1, 123.5, 69.5, 58.6, 37.3 ppm.
1
cal shifts of the H and 13C NMR signals are reported as δ values
in parts per million (ppm) relative to TMS and CDCl3, respectively.
Proton coupling patterns are described as a singlet (s), doublet (d),
triplet (t), quartet (q), or multiplet (m). Optical rotations were mea-
sured by using a Rudolph Autopol IV Polarimeter. All gas
chromatography was performed on a Perkin–Elmer Clarus 400 GC
that was equipped with a flame ionization detector (FID) and a
capillary column (30 mϫ0.25 mmϫ0.25 μm).
2-Cyclopropylisoindoline-1,3-dione (3m):[5e] White solid (79 mg,
85% yield). 1H NMR (400 MHz, CDCl3): δ = 7.82 (dd, J = 5.2,
3.2 Hz, 2 H), 7.71 (dd, J = 5.2, 3.2 Hz, 2 H), 2.74–2.68 (m, 1 H),
1.07–0.97 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.8,
133.9, 131.7, 123.4, 20.9, 5.2 ppm.
General Procedure for the Synthesis Phthalimides from 2-Iodobenza- 2-Cyclopentylisoindoline-1,3-dione (3n):[5e] White solid (96 mg, 90%
mides and Phenyl Formate: An oven-dried Schlenk tube was evacu-
yield). 1H NMR (400 MHz, CDCl3): δ = 7.81 (dd, J = 5.2, 3.2 Hz,
4
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Carbonylative Synthesis of Phthalimides and Benzoxazinones
2 H), 7.69 (dd, J = 5.2, 3.2 Hz, 2 H), 4.67–4.58 (m, 1 H), 2.13–2.06
1 H), 7.64 (d, J = 8.0 Hz, 1 H), 7.47 (t, J = 7.6 Hz, 1 H), 7.00 (d,
(m, 2 H), 2.00–1.88 (m, 4 H), 1.68–1.60 (m, 2 H) ppm. 13C NMR J = 8.5 Hz, 2 H), 3.89 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
(100 MHz, CDCl3): δ = 168.5, 133.7, 132.1, 122.9, 50.9, 29.5, δ = 163.2, 159.8, 157.1, 147.3, 136.5, 130.2, 128.5, 127.7, 126.9,
25.0 ppm.
122.5, 116.7, 114.1, 55.5 ppm. HRMS (ESI): calcd. for
[(C15H11NO3)H]+ 254.0817; found 254.0819.
2-(Cyclohexylmethyl)isoindoline-1,3-dione (3o):[5e] White solid
(102 mg, 84% yield). H NMR (400 MHz, CDCl3): δ = 7.84 (dd, J
= 5.2, 3.2 Hz, 2 H), 7.71 (dd, J = 5.2, 3.2 Hz, 2 H), 3.52 (d, J =
7.2 Hz, 2 H), 1.82–1.67 (m, 6 H), 1.25–1.14 (m, 3 H), 1.05–0.90 (m,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.6, 133.5, 132.0,
123.4, 43.9, 36.8, 30.5, 26.2, 26.1 ppm.
1
2-(p-Tolyl)-4H-Benzo[d][1,3]oxazin-4-one (7d):[6d] White solid
1
(100 mg, 85% yield). H NMR (400 MHz, CDCl3): δ = 8.22–8.17
(m, 3 H), 7.80 (t, J = 8.0 Hz, 1 H), 7.65 (d, J = 8.0 Hz, 1 H), 7.49
(t, J = 8.0 Hz, 1 H), 7.29 (d, J = 8.0 Hz, 2 H), 2.42 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 159.6, 157.2, 147.1, 143.3, 136.4,
129.5, 128.5, 128.3, 127.9, 127.4, 127.0, 116.9, 21.6 ppm. HRMS
(ESI): calcd. for [(C15H11NO2)H]+ 238.0868; found 238.0869.
2-(Quinoline-3-yl)isoindoline-1,3-dione (3s):[5d] White solid (109 mg,
80% yield). H NMR (400 MHz, CDCl3): δ = 9.06 (d, J = 2 Hz, 1
1
H), 8.813 (d, J = 2 Hz, 1 H), 8.17 (d, J = 8.4 Hz, 1 H), 8.02–8.00
(m, 2 H), 7.91–7.77 (m, 4 H), 7.62 (t, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.0, 147.9, 146.9, 134.7, 132.6, 131.6,
130.1, 129.4, 128.0, 127.6, 127.3, 125.6, 124.0 ppm.
2-(2-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (7f): White solid
(114 mg, 89% yield). H NMR (400 MHz, CDCl3): δ = 8.28 (d, J
= 7.6 Hz, 1 H), 7.92–7.85 (m, 2 H), 7.73 (d, J = 8.0 Hz, 1 H),
7.61–7.55 (m, 2 H), 7.49–7.41 (m, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 159.2, 156.6, 146.6,136.6, 133.5, 132.3, 131.4, 131.1,
129.7, 128.9, 128.6, 127.4,126.9, 117.0 ppm.
1
(S)-2-[1-(Naphthalene-2-yl)ethyl]isoindoline-1,3-dione (3t): White
solid (120 mg, 80% yield). 13C NMR (100 MHz, CDCl3): δ = 168.2,
137.6, 133.9, 133.2, 132.8, 132.0, 128.2, 128.1, 127.5, 126.3, 126.1,
126.0, 125.5, 123.2, 49.7, 17.5 ppm. [α]2D0 = 120.0 (c = 0.1, CH2Cl2).
HRMS (ESI): calcd. for [(C20H15NO2)H]+ 302.1181; found
302.1178.
(4-Oxo-4H-benzo[d][1,3]oxazin-2-yl)methyl Acetate (7l): White solid
1
(85 mg, 78% yield). H NMR (400 MHz, CDCl3): δ = 8.30 (d, J =
8.0 Hz, 1 H), 7.71–7.58 (m, 1 H), 7.46 (dd, J = 10.8, 5.0 Hz, 2 H),
4.71 (s, 2 H), 2.15 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 169.8, 166.3, 150.3, 141.0, 135.5, 123.3, 121.6, 120.6, 114.8, 62.9,
20.5 ppm. HRMS (ESI): calcd. for [(C11H9NO4)H]+ 220.0610;
found 220.0613.
(S)-2-[1-(p-Tolyl)ethyl]isoindoline-1,3-dione (3u): White solid
1
(113 mg, 86% yield). H NMR (400 MHz, CDCl3): δ = 7.80–7.76
(m, 2 H), 7.68–7.63 (m, 2 H), 7.39 (d, J = 8 Hz, 2 H), 7.12 (d, J =
8 Hz, 2 H), 5.53 (q, J = 7.2 Hz, 1 H), 2.30 (s, 3 H), 1.90 (d, J =
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.2, 137.4,
137.3, 133.9, 132.0, 129.2, 127.4, 123.2, 49.4, 21.1, 17.6 ppm. [α]2D0
= –33.5 (c = 0.1, CH2Cl2).
2-(3-Methylbenzofuran-2-yl)-4H-benzo[d][1,3]oxazin-4-one (7m):[16]
1
White solid (110 mg, 80% yield). H NMR (400 MHz, CDCl3): δ
= 8.23 (d, J = 8.0 Hz, 1 H), 7.85–7.76 (m, 2 H), 7.66–7.60 (m, 2
H), 7.53–7.45 (m, 2 H), 7.33–7.29 (m, 1 H), 2.76 (s, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 158.5, 154.9, 151.7, 146.9, 140.5,
136.7, 129.6, 128.7, 128.5, 128.0, 127.8, 125.1, 123.3, 120.9, 116.6,
112.1, 9.9 ppm.
Ethyl (S)-2-(1,3-Dioxoisoindolin-2-yl)-3-phenylpropanoate (5a):
Light yellow oil (119 mg, 74% yield). 1H NMR (400 MHz, CDCl3):
δ = 7.77 (dd, J = 5.4, 3.1 Hz, 2 H), 7.68 (dd, J = 5.5, 3.0 Hz, 2 H),
7.20–7.11 (m, 5 H), 5.14 (dd, J = 11.2, 5.3 Hz, 1 H), 4.26–4.23 (m,
J = 7.1, 2.7 Hz, 2 H), 3.57 (m, 2 H), 1.25 (t, J = 7.1 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 168.8, 167.5, 136.8, 134.0, 131.6,
128.8, 128.5, 126.8, 123.4, 62.0, 53.4, 34.6, 14.1 ppm. [α]2D0 = –58.00
(c = 0.1, CH2Cl2). HRMS (ESI): calcd. for [(C19H17NO4)H]+
324.1236; found 324.1232.
6-Chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (7n):[6d] White so-
lid (96 mg, 75% yield). 1H NMR (400 MHz, CDCl3): δ = 8.31–8.28
(m, 2 H), 8.16 (d, J = 8.0 Hz, 1 H), 7.69 (d, J = 4 Hz, 1 H), 7.62–
7.46 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 158.7, 158.3,
148.0, 142.9, 133.0, 129.9, 129.8, 128.8, 128.7, 128.5, 127.0,
115.8 ppm. HRMS (ESI): calcd. for [(C14H8ClNO2)H]+ 258.0322;
found 258.0321.
Methyl (S)-2-(1,3-Dioxoisoindolin-2-yl)propanoate (5b): Yellow oil
1
(99 mg, 85% yield). H NMR (400 MHz, CDCl3): δ = 7.85 (dd, J
Supporting Information (see footnote on the first page of this arti-
1
= 5.5, 3.0 Hz, 2 H), 7.73 (dd, J = 5.5, 3.1 Hz, 2 H), 4.96 (q, J =
7.3 Hz, 1 H), 3.73 (s, 3 H), 1.68 (d, J = 7.3 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 170.2, 167.4, 134.1, 131.9, 123.5,
52.7, 47.4, 15.2 ppm. [α]2D0 = –3.0 (c = 0.1, CH2Cl2). HRMS (ESI):
calcd. for [(C12H11NO4)H]+ 234.0766; found 234.0769.
cle): Decomposition study of phenyl formate and copies of H and
13C NMR spectra.
Acknowledgments
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one (7a):[6d] White solid (97 mg,
S. P. C. gratefully acknowledges the Council of Scientific and In-
dustrial Research (CSIR), New Delhi for providing a senior re-
search fellowship (SRF).
1
87% yield). H NMR (400 MHz, CDCl3): δ = 8.30–8.21 (m, 3 H),
7.83–7.79 (m, 1 H), 7.68 (d, J = 8.0 Hz, 1 H), 7.58–7.48 (m, 4
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.5, 157.0, 146.9,
136.5, 132.6, 130.2, 128.9, 128.7, 128.5, 128.2, 127.2, 117.0 ppm.
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2-(4-Methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one (7c):[6d] White
1
solid (113 mg, 90% yield). H NMR (400 MHz, CDCl3): δ = 8.26
(d, J = 8.4 Hz, 2 H), 8.22 (d, J = 7.9 Hz, 1 H), 7.80 (t, J = 7.7 Hz,
Eur. J. Org. Chem. 0000, 0–0
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Job/Unit: O50109
/KAP1
Date: 26-02-15 14:33:19
Pages: 7
S. P. Chavan, B. M. Bhanage
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Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O50109
/KAP1
Date: 26-02-15 14:33:19
Pages: 7
Carbonylative Synthesis of Phthalimides and Benzoxazinones
Annulated Heterocycles
S. P. Chavan, B. M. Bhanage* .......... 1–7
Carbonylative Synthesis of Phthalimides
and Benzoxazinones by Using Phenyl For-
mate as a Carbon Monoxide Source
Keywords: Synthetic methods / Nitrogen
heterocycles / Carbonylation / Cyclization /
Palladium
A simple and efficient palladium-catalyzed
carbonylative cyclization of N-substituted
2-iodobenzamides and 2-iodoanilides was
investigated for the synthesis of phthali-
mides and benzoxazinones, respectively, by
using phenyl formate as a CO source.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7