Silver-Mediated Synthesis of 4H-Benzoxazin-4-ones by Intramolecular Decarboxylative O-Acylation Reactions with α-Oxocarboxylic Acid

Article abstract of DOI:10.1002/ejoc.201700176

The first example of an intramolecular decarboxylative acylation reaction for the synthesis of 4H-benzoxazin-4-one derivatives has been described. The silver-mediated reaction has a broad substrate scope and provides a mild and rapid approach to the corre

Full text of DOI:10.1002/ejoc.201700176

A Journal of
Accepted Article
Title: Silver mediated synthesis of 4H-benzoxazin-4-ones by
intramolecular decarboxylative O-acylation reactions with ꢀ
-oxocarboxylic acid
Authors: kuppusamy bharathimohan, thanasekaran ponpandian, and
Ahamed A Jafar
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700176
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10.1002/ejoc.201700176
European Journal of Organic Chemistry
FULL PAPER
Silver mediated synthesis of 4H-benzoxazin-4-ones by
intramolecular decarboxylative O-acylation reactions with
-oxocarboxylic acid
Kuppusamy Bharathimohan,[a,b] Thanasekaran Ponpandian,[b] and Ahamed A Jafar*[a]
Abstract: The first example of intramolecular decarboxylative
acylation reaction with α-oxocarboxylic acid has been described.
This method offers a mild and rapid synthesis of 4H-benzoxazin-4-
ones derivatives in high yields with silver salt.
The 4H-benzoxazin-4-ones represent
a class of important
scaffolds displaying wide range of application in
a
pharmaceuticals[4] (Figure 1). Particularly, 2-substituted 4H-
benzoxazin-4-one derivatives show remarkable biological
activity such as chymotrypsin inactivators,[4c] C1r protease
inhibitor,[4d] HDL elevators[4e] and pancreatic lipase inhibitor.[4f] In
addition, 2-substituted 4H-benzoxazin-4-ones are used as a key
raw material for the synthesis of quinazolinone analogues and
its derived pharmaceuticals.[5] Therefore, demand to devise
versatile methodologies for the construction of 4H-benzoxazin-4-
ones is growing. The cyclisation of anthranilic acid, N-acyl
anthranilic acid and isotoic anhydride[6] are commonly used
methods to contruct 4H-benzoxazin-4-ones. Other improved
methods include the electrochemical cyclisation of o-
trichloroacetylanilide[6] and imine cyclisation using hypervalent
iodine (PIDA).[7] They are also synthesized by palladium
catalyzed carbonylative reactions of N-(o-haloaryl)amides using
CO gas[8a-8e] or CO surrogates such as paraformaldehyde,[8f]
phenylformate[8g,8h] and oxalylchloride.[8i]
Introduction
Transition metal catalyzed decarboxylative cross coupling
reaction is an effective and attractive method for the generation
of carbon-carbon or carbon-heteroatom bond.[1] In the recent
years, the decarboxylative acylation reactions has generated
considerable attention for accessing aryl ketone by using α-
oxocarboxylic acid as an acyl surrogates, which was
accomplished by several metal directing groups via sp2 C-H
activation.[2] However, besides these fruitful accomplishments,
all those reports provide the facile access of aryl ketones by
intermolecular decarboxylative acylation and this methodology
further not extended to intramolecular acylation reaction.
Moreover, the decarboxylative O-acylation has also not been
addressed so far in the literature with α-oxocarboxylic acid.
Recently, Luo et al reported the radical pathway synthesis of
phenanthridinones through intramolecular decarboxylative
amidation reaction.[3]
Scheme 1 Approach of decarboxylative acylation reaction
Previous work
O
DG
DG
Pd catalyst
OH
+
Figure 1 Selected bioactive molecules of 4H-benzoxazin-4-one
Aryl
O
O
O
O
Br
Aryl
DG = Directing Group
O
O
N
N
O
This work
O
N
OH
HDL elevator
Cetilistat(anti-obesity)
phase-III drug
O
Oxidants
Ag salt
O
O
H
N
N
O
O
N
O
I
O
O
O
N
N
Other notable methods are TM-catalyzed or TM-free synthesis
of 4H-benzoxazin-4-ones from 2-azidoalkynylbenzene,[9] 2-aryl
indole[10] and N-benzoyl-2-iodobenzamide.[11] Very recently, Du
et al[12] described the CoCl2/TBHP mediated intramolecular
oxidative cyclisation of N-(2-formylphenyl)amides. Thus,
catalytic aza-Wittig reaction of 2-azido phenyl anhydride
described by Huang and Ding groups.[13] During the preparation
of this manuscript Gogai group[14] published the copper
catalyzed C-N, C-O coupling reaction of aryl glyoxylicacid with
C1r serine protease inhibitor
AX-9657
[a]
[b]
K. Bharathimohan, Jafar A. Ahamed
PG and Research Department of Chemistry
Jamal Mohamad College, Affiliated to Bharathidasan University
Thiruchirapalli - 620020, Tamil Nadu, India
E-mail: agjafar@yahoo.co.in
K. Bharathimohan, T. Ponpandian
Drug Discovery Research Division
Orchid Chemicals & Pharmaceuticals Ltd
R&D center, Sholinganallur, Chennai - 600119, Tamil Nadu, India
isatins. Earlier, we demonstrated that
a
sequential
decarboxylative coupling reaction for the synthesis of polycyclic
triazoles.[15] Leveraging from our previous experience on the
decarboxylative coupling reactions, we describe herein
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201700176
European Journal of Organic Chemistry
FULL PAPER
development of a new approach to the synthesis of 4H-
benzoxazin-4-ones via intramolecular decarboxylative O-
acylation reactions with -oxocarboxylic acid (Scheme 1). The
distinctive features of this work include, first intramolecular
decarboxylative acylation, inexpensive reagents, broad
substrate scope and one pot sequence from N-aroyl isatin.
such as PIDA, oxone and (NH4)2S2O8, affording 2a in 40%, 28%
and 65% yield respectively (Table 1, Entries 2-4). To our delight
the use of K2S2O8 as oxidant showed clean conversion to
desired product and the 2a was isolated in 88% yield within 3h
(Table 1, Entry 5). Efforts to decrease the amount of silver salts
showed inconvincing results while use of excess silver salt led to
similar results (Table 1, Entry 6 and 7). Use of other solvents
such as 1,2-DCE, DME, dioxane, toluene and DMF were failed
to improve the product yield (Table 1, Entries 8-12), while
acetonitrile found to be more suitable solvent for this reaction.
We have subjected various silver salts in the reaction by
replacing Ag2O with AgNO3, AgOAc and Ag2CO3 which provided
40%, 15% and 81% of 2a respectively (Table 1, Entries 13-15).
As control experiments, no product formation was observed, if
only Ag2O or K2S2O8 were used (Table 1, Entries 16 and 17).
The formation of 2aa was not observed under the optimized
reaction condition.
Results and Discussion
In our initial study, 2-(2-benzamido)phenyl)-2-oxoacetic acid (1a)
was selected as a modal substrate for the optimization of
intramolecular decarboxylative acylation reaction. Here, two
types of acylation reactions are possible such as O-acylation or
sp2 C-H acylation which may leads to either 4H-benzoxazin-4-
ones (2a) or 5H-dibenzo [b,e]azepine-6-11-dione (2aa)
respectively. The reaction was first investigated with Ag2O (1
eq.) and TBHP (2 eq.) as an oxidant in acetonitrile (ACN) at
reflux condition led to the formation of 2a in 25% yield (Table 1,
Entry 1) and formation of 2aa was not observed. The product 2a
was confirmed by NMR, Mass and IR spectroscopy. With this
result, next we screened the reaction with different oxidant,
We next explored the scope of this reaction with various
substituted 2-benzamidophenyl-2-oxoacetic acid under the
optimized reaction conditions and the results are summarized in
Scheme 2. Both electron donating (OMe, Me, Et) and electron
withdrawing (F, Cl, NO2, benzoyl) substitution in 4th or 3rd
position of benzamide ring does not affect the product yield
which gave the corresponding benzoxazinones in 79-91% (2b-
2m). Whereas, the benzamide ring substituted with 2-chloro (2n),
3,5-dimethoxy (2o) and 3,4,5-trimethoxy (2p) afforded the
product in 76%-78% yield. Replacing benzamide ring with 2-
thiophene (2q) and 1-naphthyl (2r) also showed good reactivity
which gave 88% and 92% respectively. To extent the substrate
scope of 2-amidophenyl glyoxalic acid ring, substituted with Br,
F and OMe were all provided excellent yield of corresponding
cyclized product (2s-2u). Notably, the compound 2v is HDL
elevator was synthesized in 85% yield in our reaction condition.
The aliphatic amides 1w and 1x were examined under our
reaction condition (Scheme 3). Surprisingly, the instability of
corresponding cyclized product 2w and 2x were observed, it
converted into 2-amido anthranilic acid derivatives 3a and 3b
respectively. Mass analysis and TLC Rf value (near with 2a) of
crude reaction mixture confirmed the formation of 2w and 2x but
failed to isolate and thus led to ring opening reaction with water
during isolation, which produces 3a and 3b respectively. The
key starting material 1 was synthesized from isatin derivative
(Scheme 4)
Table 1 Optimization of reaction conditions[a]
OH
O
O
O
O
Silver salt, oxidant
Solvent, reflux
O
+
H
N
N
N
H
O
O
1a
2a
2aa
Entry
Silver salt
(1 eq.)
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Oxidant
(1 eq.)
solvent
Time
(h)
12
12
12
12
3
Yield[b]
2a (%)
25
1[c]
2
TBHP
ACN
ACN
PIDA
40
3
Oxone
ACN
28
4
(NH4)2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
ACN
65
5
ACN
88
6[d]
7[e]
8
ACN
12
3
50
ACN
87
DCE
8
20
9
DME
Dioxane
8
-
10
8
10
11
12[f]
13
Ag2O
Ag2O
K2S2O8
K2S2O8
K2S2O8
Toluene
DMF
8
8
3
35
45
40
Scheme 3 Decarboxylative acylation of aliphatic amides
O
AgNO3
ACN
O
O
O
HO
14
15
16
17
AgOAc
Ag2CO3
Ag2O
-
K2S2O8
K2S2O8
-
ACN
ACN
ACN
ACN
3
5
15
81
H
OH
NH
Ag2O, K2S2O8
ACN, reflux, 4h
N
O
O
N
12
12
trace
-
O
1w
2w
3a
K2S2O8
O
[a] 1a (0.2 g), silver salt (1 eq.), oxidant (1 eq.), solvent (5 mL),
reflux. [b] Isolated yield. [c] 2 eq. of TBHP. [d] 0.5 eq. Ag2O. [e]
1.5 eq. Ag2O [f] Reaction at 100oC
O
O
N
OH
NH
O
Ag2O, K2S2O8
ACN, reflux, 4h
HO
O
H
N
O
O
1x
2x
3b
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10.1002/ejoc.201700176
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Scheme 2 Synthesis of 4H-benzoxazin-4-ones derivatives
OH
O
N
O
Ag2O (1 eq.)
O
O
H
R2
K2S2O8 (1 eq.)
R1
N
ACN, reflux
O
R1
R2
1a-1v
2a-2v
O
N
O
O
N
O
O
N
O
N
O
N
O
O
O
Br
F
O
2b, 3.5h, 85%
2e, 4h, 86%
2c, 3h, 90%
2d, 4h, 81%
2a, 3h, 88%
O
O
O
O
O
N
O
O
N
O
O
N
O
O
N
N
Ph
CF3
NO2
2j, 3h, 79%
O
2i, 3h, 81%
2g, 3h, 91%
2f, 3.5h, 79%
2h, 4.5h, 87%
O
O
O
O
N
O
O
N
O
O
N
O
Cl
O
O
N
F
NO2
Cl
N
O
2m, 3.5h, 85%
2o, 4h, 78%
2k, 4.5h, 85%
2n, 3h, 76%
2l, 4h, 83%
O
O
Br
O
N
O
N
O
O
O
O
O
N
S
N
O
O
2s, 4.5h, 88%
2r, 3h, 92%
2q, 4h, 88%
2p, 6h, 76%
O
O
N
O
N
O
Br
F
O
O
O
N
F
2u, 3.5h, 90%
2v, 4.5h, 85%
2t, 2.5h, 88%
This methodology was further extended to synthesize 4H-
benzoxazin-4-ones from N-aroyl isatins by one pot fashion via
in-situ hydrolysis followed by decarboxylative O-acylation
sequence (Scheme 5). Water included into this reaction
medium.
Scheme 4 Synthesis of 2-(2-substituted benzamido)phenyl)-2-
oxoacetic acid
condition as
oxocarboxylic acid
conversion of 4a to 2a was achieved with Ag2O (1 eq), K2S2O8 (1
eq), ACN:H2O (8:2) at reflux for 3h in 74% yield. But, prolonged
reaction maintenance for 8h led to the formation of 3c in 72%
due to the hydrolysis of 2a with water present in the reaction
a
hydrolytic agent which produces the -
from N-aroyl isatins. The one-pot
O
O
Ar-COCl
O
1
COOH
Ar
Et3N (2 eq.)
K2CO3 (1 eq.)
R1
O
R1
O
R1
H2O, 100oC
1h
NH
N
DCM, rt, 6h
N
H
Ar
O
O
1
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10.1002/ejoc.201700176
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No reaction was observed in the absence of water, meanwhile
we found that K2S2O8 acts as a base for the hydrolysis of 4 to 1.
It is noted that K2S2O8 serves as an oxidant as well as base for
this one-pot reaction. With these observations, the methodology
was extended to 4-chloro benzoyl isatin (4b) and 4-iodo benzoyl
isatin (4c) under these conditions which provided corresponding
benzoxazinones (2y & 2z) 78% and 80% respectively in 3h
(Scheme 5).
interacted with oxidants (Ag2O & K2S2O8) and suspected that
carboxylic acid 3c or carboxaldehyde 5a formed as an
intermediate, which may undergo subsequent reaction to yield
2a. The formation of carboxaldehyde and carboxylic acid
derivatives were not observed during the preparation of 2 from 1
under this reaction condition. Further, control experiments were
conducted to study the reaction pathway . When 3c and 5a were
exposed to our reaction condition, the desired product 2a
obtained only 6% and 14% respectively (Scheme 7). These
results clearly states that the formation of 2a from 1a does not
proceed through 3c and 5a intermediates.
Scheme
5 One pot conversion of N-aroyl isatin to 4H-
benzoxazin-4-ones
O
Scheme 7 Control experiments with 3c and 5a
O
O
Ag2O (1 eq.)
OH
O
K2S2O8 (1 eq.)
O
O
Ag2O (1 eq.),
+
HO
O
NH
N
H
N
K2S2O8 (1 eq.)
O
ACN:H2O (8:2)
reflux
N
O
O
ACN (5 ml), Reflux
3 h
N
R
R
O
R
2a
3c
3c
2a, 6%
4a-4c
74%
R = H; 3h
R = H; 8h
0%
O
O
H
Ag2O (1 eq.),
0%
HO
O
72%
H
O
H
N
K2S2O8 (1 eq.)
N
+
N
ACN (5 ml), Reflux
3 h
O
O
O
N
O
N
O
N
5a
2a, 14%
3c, 10%
O
O
O
Further experiment was conducted to obtain insight into the
reaction mechanism, the yield of 2a was not affected in the
presence of radical trapping reagent TEMPO (1.0 eq or 2.0 eq),
which suggest that the reaction may not be mediated by radical.
Mechanism of the reaction remains unclear on the basis of our
experimental results and previous literature[17]. The proposed
mechanism of the reaction was shown in Scheme 8. It is
believed that this transformation starts with acyl silver species
(A) from 1 in presence of Ag2O/K2S2O8 and then with additional
Ag(I) salt and sulphate anion to produce high valent silver
complex (B). Reductive elimination of B provides the desired
product 2.
I
Cl
2a, 3h, 74%
2y, 3h, 78%
2z, 3h, 80%
To further examine the synthetic potential of our protocol, we
also conducted a gram scale reaction by choosing 2-(2-
benzamido)phenyl)-2-oxoacetic acid (10 mmol, 2.7 g) as the
substrate under the optimized reaction condition, the desired
product (2a) could be isolated in 87% yield, which confirms its
suitability of large scale reaction (Scheme 6).
Scheme 6 Gram scale reaction of 2-(2-benzamido)phenyl)-2-
oxoacetic acid
Scheme 8 Proposed reaction mechanism of formation of 2
O
N
OH
Ag2O (2.32 g)
O
O
O
O
O
COOH
O
H
K2S2O8 (2.71 g)
H
N
N
Ag2O
Ag(I)
O
Ag(II)
O
R
ACN (40 mL)
reflux, 4h
2
S2O8
O
O
N
.
N
H
R
2
SO4
-CO2
HSO4
87%
R
1
A
B
10 mmol, 2.7 g
8.73 mmol, 1.95 g
RE
In order to reveal the detailed transformation of this reaction, a
stability and reactivity of α-keto acids was studied in the
literature. In 1983, Cooper et al[16] reviewed the synthesis and
properties of α-keto acids. Here reported that thermal and
oxidative decarboxylation of α-keto acids produces the
corresponding carboxaldehyde and carboxylic acid respectively
in the presence of various oxidants or transition metal catalyst
(Pd, Os or Ru). Under our reaction condition α-keto acids (1a)
O
O
N
R
2
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10.1002/ejoc.201700176
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Characterization data:
Conclusions
2-(2-Benzamidophenyl)-2-oxoacetic acid (1a): White solid; 1H NMR
(400 MHz, DMSO-d6) δ 11.37 (s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.94 (t, J
= 7.2 Hz, 2H), 7.72-7.77 (m, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.57 (t, J = 7.2
Hz, 2H), 7.34 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ 190.9,
165.9, 165.3, 140.3, 135.8, 134.3, 132.7, 132.6, 129.4, 129.3, 127.8,
124.5, 122.6, 122.4; ESI-MS (M+1) 270.1
In summary, we have developed an alternative methodology for
the synthesis of 4H-benzoxazin-4-ones derivatives through silver
mediated intramolecular decarboxylative O-acylation of amide
oxygen with α-oxocarboxylic acid. This work represents the first
example of intramolecular decarboxylative acylation reaction.
Our methodology is operationally mild, broad substrate scope,
and is amenable to the gram-scale synthesis of 4H-benzoxazin-
4-ones. Furthermore, the same method has been applicable for
the conversion of N-aroyl isatin to 4H-benzoxazin-4-ones via
insitu hydrolysis, and decarboxylative cyclisation.
1-(Phenylcarbonyl)-1H-indole-2,3-dione (3a): Yellow solid; 1H NMR
(400 MHz, CDCl3) δ 8.02 (d, J = 8.4 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H),
7.74-7.77 (m, 3H), 7.65 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), 7.36
(t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): 180.6, 168.4, 157.6,
148.5, 137.9, 134.2, 133.4, 130.1, 128.5, 127.8, 125.7, 124.9, 120.4,
116.5; ESI-MS (M+1) 252.1
.
1-[(4-Chlorophenyl)carbonyl]-1H-indole-2,3-dione (3b): Yellow color
solid; 1H NMR (400 MHz, DMSO-d6) δ 7.94 (d, J = 7.6 Hz, 1H), 7.88 (d, J
= 8.4 Hz, 2H), 7.78 (t, J = 8.0 Hz, 2H), 7.58 (d, J = 8.4 Hz, 2H), 7.37 (t, J
= 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): 180.4, 167.4, 157.6, 148.2,
138.3, 137.9, 133.1, 131.9, 129.8, 129.3, 128.7, 125.8, 124.9, 120.5,
116.6; ESI-MS (M+1) 286.2
Experimental Section
General
procedure
for
the
preparation
of
substituted
benzamidophenyl-2-oxoacetic acid (1): To
a
stirred solution of
substituted isatins (2.04 mmol) and triethylamine (4.08 mmol) in
dichloromethane (10 mL) was added acid chloride (2.24 mmol) at 0 °C.
The resulting reaction mixture was warmed to rt and stirred for 6h.
Reaction was monitored by TLC. The reaction mixture was distilled under
vacuum and obtained residue was mixed with water (10 mL) and K2CO3
(2.04 mmol) then heated to 100 °C for 1 h. Cooled to rt and pH was
adjusted to 1-2 using aqueous HCl (1:1), obtained solid was filtered and
washed with water (20 mL) then dried. Solid was further triturated with
diethyl ether (10 mL) to afford pure 1
1-[(4-Iodophenyl)carbonyl]-1H-indole-2,3-dione (3c): Yellow color
solid; 1H NMR (400 MHz, DMSO-d6) δ 7.89-7.94 (m, 3H), 7.77 (t, J = 8.4
Hz, 2H), 7.63 (d, J = 8.4 Hz, 2H), 7.37 (t, J = 7.6 Hz, 1H); 13C NMR (100
MHz, DMSO-d6): 180.4, 167.8, 157.6, 148.2, 138.0, 137.9, 137.5, 133.7,
131.7, 131.5, 125.8, 124.9, 120.5, 116.6, 101.7; ESI-MS (M+1) 378.1
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one (2a):[7] White solid; m.p. 124-
126 °C; IR (KBr) 3039, 1764, 1613,1474, 1314, 1259, 1039, 764, 684
cm-1; 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 7.6 Hz, 2H), 8.25 (d, J =
8.0 Hz, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.50−7.60
(m, 4H); 13C NMR (100 MHz, CDCl3): δ 159.6, 157.1, 146.9, 136.6, 132.6,
130.2, 128.7, 128.6, 128.3, 128.2, 127.2, 117.0,; Anal. Calcd. for
C14H9NO2: C, 75.33; H, 4.06; N, 6.27. found C, 75.24; H, 4.11; N, 6.22;
ESI-MS (M+1) 224.2
General procedure for the preparation of substitituted N-aroyl isatin
(4): To a stirred solution of isatin (3.40 mmol) and triethylamine (6.80
mmol) in dichloromethane (15 mL) was added acid chloride (4.08 mmol)
at 0 °C, and the resulting reaction mixture was slowly brought to rt and
stirred for 6h. Reaction was monitored by TLC. Diethyl ether (15 mL) was
added to the reaction mixture. Precipitated solid was filtered, washed
Et2O (15 mL), dried to afford pure 4.
2-(4-Methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one (2b):[12] White
solid; mp 146-148 °C; IR (KBr) 2924, 1759, 1616, 1600, 1566, 1470,
1253, 1170, 1059, 679 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.26-8.29 (m,
2H), 8.22-8.24 (m, 1H), 7.78-7.83 (m, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.5 (t,
J = 7.24 Hz, 1H), 6.99-7.03 (m, 2H), 3.9 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 163.4, 159.9, 157.2, 147.4, 136.6, 130.4, 128.7, 127.8, 127.0,
122.6, 116.8, 114.3, 55.6; Anal. Calcd. for C15H11NO3: C, 71.14; H, 4.38;
N, 5.53. found C, 71.53; H, 4.24; N, 5.61; ESI-MS (M+1) 254.2
Preparation of benzo[d][1,3]oxazin-4-ones (2a-2v): To
a stirred
solution of 2-(2-benzamido)phenyl)-2-oxoacetic acids 1 (0.2 g, 0.74
mmol) in acetonitrile (5 mL) was added K2S2O8 (0.74 mmol) and Ag2O
(0.74 mmol) at rt. The reaction mixture was heated to reflux for 2.5-7h.
Reaction was monitored by TLC. Ethyl acetate (20 mL) was added to the
reaction mixture under stirring, filtered through a pad of celite, filtrate was
distilled under reduced pressure. The obtained residue was purified by
silica gel column chromatography using hexane/ethylacetate (2-5%) as
eluent to afford pure 2a-2u (76-92%).
2-(4-Fluorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2c):[7] White solid;
m.p. 166-168 °C; IR (KBr) 3072, 2926, 1769, 1623, 1513, 1475, 1322,
1063, 843, 770 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.32-8.36 (m, 2H),
8.24 (d, J = 7.84 Hz, 1H), 7.82-7.86 (m, 1H), 7.68 (d, J = 8.04 Hz, 1H),
7.53 (t, J = 7.24 Hz, 1H), 7.20 (t, J = 8.64 Hz, 2H); 13C NMR (100 MHz,
CDCl3): δ 165.7 (d, J = 252.7 Hz), 159.5, 156.4, 147.1, 136.7, 130.8 (d, J
= 9.1 Hz), 128.8, 128.4, 127.3, 126.7, 117.0, 116.1 (d, J = 21.9 Hz); Anal.
Calcd. for C14H8FNO2: C, 69.71; H, 3.34; N, 5.81. found C, 69.58; H,
3.25; N, 5.92; ESI-MS (M+1) 242.2
Procedure for the preparation of 2a, 2y and 2z from N-aroyl isatins:
To
a stirred solution of N-aroyl isatins 4 (0.1 g, 0.39 mmol) in
Acetonitrile:Water (4:1, 5 mL) was added K2S2O8 (0.39 mmol) and Ag2O
(0.39 mmol) at rt. The resulting reaction mixture was heated to reflux for
3h. Reaction was monitored by TLC. Reaction mixture was diluted with
EtOAc (20 mL), and filtered through a pad of celite, filtrate was washed
with water (20 mL), brine solution (15 mL) and dried over anhydrous
Na2SO4. Solvent was removed by distillation under vacuum and the
obtained residue was purified by silica gel column chromatography using
hexane/ethylacetate (2-5%) as eluent to afford pure product (74-80%).
2-(4-Ethylphenyl)-4H-benzo[d][1,3]oxazin-4-one (2d): White solid; m.p.
148-151 oC; IR (KBr) 3133, 1701, 1661, 1611, 1589, 1273, 755 cm-1; 1H
NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.4 Hz, 3H), 7.79-7.83 (m, 1H),
7.68 (d, J = 8.0 Hz, 1H), 7.50 (t, J = 6.8 Hz, 1H), 7.34(d, J = 8.0 Hz, 2H),
2.74 (q, J = 7.2 Hz, 2H), 1.28 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 159.6, 157.3, 149.5, 147.1, 136.4, 128.5, 128.4, 128.2, 127.9,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700176
European Journal of Organic Chemistry
FULL PAPER
127.6, 127.1, 116.9, 29.3, 15.1 ; Anal. Calcd. for C16H13NO2: C, 76.48; H,
5.21; N, 5.57. found C, 76.39; H, 5.27; N, 5.59; ESI-MS (M+1) 252.2
948, 768, 689 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.0 Hz, 1H),
8.11 (d, J = 7.6Hz, 1H), 8.02 (d, J = 9.6 Hz, 1H), 7.85 (t, J = 7.6 Hz, 1H),
7.71 (d, J = 7.6 Hz, 1H), 7.46-7.56 (m, 2H), 7.27-7.30 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ 162.9 (d, J = 245.4 Hz), 159.2, 156.0, 146.7, 136.8,
132.5(d, J = 8.1 Hz), 130.5 (d, J = 7.8 Hz), 128.7, 127.4, 124.1 (d, J = 3.2
Hz), 119.7 (d, J = 21.2 Hz), 117.1, 115.3 (d, J = 24 Hz); Anal. Calcd. for
C14H8FNO2: C, 69.71; H, 3.34; N, 5.81. found C, 69.52; H, 3.29; N, 5.95;
ESI-MS (M+1) 242.2
2-(4-Bromophenyl)-4H-benzo[d][1,3]oxazin-4-one (2e):[7] White solid;
m.p. 182-184 oC; IR (KBr) 1764, 1620, 1485, 1257, 1008, 834, 774 cm-1;
1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 7.84 Hz, 1H), 8.18 (d, J = 8.68
Hz, 2H), 7.83-7.87 (m, 1H), 7.65-7.77 (m, 3H), 7.54 (t, J = 7.24 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ 159.4, 156.5, 146.9, 136.8, 132.2, 129.9,
129.3, 128.8, 128.6, 127.8, 127.4, 117.13, Anal. Calcd. for C14H8BrNO2:
C, 55.66; H, 2.67; N, 4.64. found C, 55.13; H, 2.72; N, 4.84; ESI-MS
(M+1) 303.2
2-(3-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2l):[8g] White solid;
m.p. 153-155 oC; IR (KBr) 1767, 1626, 1605, 1488, 1405, 1325, 1259,
1223, 1095, 1024, 838, 763 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.32 (s,
1H), 8.25 (d, J = 7.72 Hz, 1H), 8.2 (d, J = 7.84 Hz, 1H), 7.85 (t, J = 7.88
Hz, 1H), 7.71 (d, J = 8.08 Hz, 1H), 7.55 (t, J = 6.16 Hz, 2H), 7.46 (t, J =
7.88 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 159.1, 155.8, 146.6, 136.7,
134.9, 132.6, 132.0, 130.0, 128.7, 128.6, 128.3, 127.3, 126.3, 117.0;
Anal. Calcd. for C14H8ClNO2: C, 65.26; H, 3.13; N, 5.44. found C, 65.23;
H, 3.15; N, 5.43; ESI-MS (M+1) 258.2
2-(4-Trifluoromethylphenyl)-4H-benzo[d][1,3]oxazin-4-one
(2f):[12]
°
White solid; m.p. 126-128 C; IR (KBr) 3435, 1762, 1617, 1605, 1568,
1473, 1260, 1179, 1065, 854, 785 cm-1; 1H NMR (400 MHz, CDCl3) δ
8.37 (d, J = 8.2 Hz, 2H), 8.19-8.21 (m, 1H), 7.78-7.82 (m, 1H), 7.67-7.72
(m, 3H), 7.48-7.52 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 159.1, 155.9,
146.7, 136.8, 133.7, 129.0, 128.9, 128.7, 127.6, 125.8 (q, J = 3.6 Hz),
117.3, Anal. Calcd. for C15H8F3NO2: C, 61.86; H, 2.77; N, 4.81. found C,
61.79; H, 2.71; N, 4.89; ESI-MS (M+1) 292.1
2-(3-Nitroophenyl)-4H-benzo[d][1,3]oxazin-4-one (2m): Light yellow
color solid; m.p. 162-165 oC; IR (KBr) 1766, 1621, 1595, 1519, 1356,
1319, 1067, 1035, 774, 686 cm-1; 1H NMR (400 MHz, CDCl3) δ 9.18 (s,
1H) 8.64 (d, J = 7.8 Hz, 2H), 8.43 (d, J = 8.24 Hz, 1H), 8.28 (d, J = 7.84
Hz, 1H), 7.87-7.91 (m, 1H), 7.71-7.77 (m, 2H), 7.6 (t, J = 7.24 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ 158.8, 154.9, 148.8, 146.4, 137.0, 133.7,
132.3, 130.0, 129.2, 128.9, 127.6, 126.9, 123.4, 117.2; Anal. Calcd. for
C14H8N2O4: C, 62.69; H, 3.01; N, 10.44. found C, 62.51; H, 3.16; N,
10.02; ESI-MS (M+1) 269.2
2-(4-Nitrophenyl)-4H-benzo[d][1,3]oxazin-4-one (2g):[8g] Light yellow
color solid; m.p. 190-193 oC; IR (KBr) 1763, 1618, 1593, 1517, 1354,
1317, 1065, 1035, 773, 686 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J
= 8.68 Hz, 2H), 8.36 (d, J = 8.64 Hz, 2H), 8.28 (d, J = 7.76 Hz, 1H), 7.89
(t, J = 7.48 Hz, 1H), 7.75 (d, J = 8.08 Hz, 1H), 7.61 (t, J = 7.72 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ 158.8, 155.0, 150.3, 146.4, 137.0, 136.0,
129.4, 129.3, 128.9, 127.8, 124.0, 117.2, Anal. Calcd. for C14H8N2O4: C,
62.69; H, 3.01; N, 10.44. found C, 62.58; H, 3.12; N, 10.09; ESI-MS
(M+1) 269.2
2-(2-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2n):[8g] White solid;
m.p. 136-138 oC; IR (KBr) 1768, 1625, 1475, 1440, 1315, 1272, 1223,
1092, 1029, 1003, 761cm-1; 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 7.6
Hz, 1H), 7.90 (d, J = 6.4 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.4
Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.53(d, J = 8.0 Hz, 1H), 7.47 (t, J = 6.0
Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 159.3,
156.7, 146.6, 136.7, 133.3, 132.6, 131.6, 131.2, 130.5, 129.1, 128.7,
127.6, 127.0, 117.1; Anal. Calcd. for C14H8ClNO2: C, 65.26; H, 3.13; N,
5.44. found C, 65.21; H, 3.18; N, 5.49; ESI-MS (M+1) 258.2
2-(4-Benzoylphenyl)-4H-benzo[d][1,3]oxazin-4-one (2h): White solid;
m.p. 182-185 oC; IR (KBr) 1764, 1740, 1651, 1474, 1306, 1064, cm-1; 1H
NMR (400 MHz, CDCl3) δ 8.44 (d, J = 8.48 Hz, 2H), 8.28 (d, 7.88 Hz, 1H),
7.93 (d, J = 8.48 Hz, 2H), 7.82-7.89 (m, 3H), 7.74 (d, J = 8.0, 1H), 7.64 (t,
J = 7.36 Hz, 1H), 7.52-7.59 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 195.9,
159.2, 156.2, 146.7, 140.9, 137.0, 136.7, 133.5, 132.9, 130.2, 130.1,
128.8, 128.7, 128.5, 128.2, 127.5, 117.1; Anal. Calcd. for C21H13NO3: C,
77.05; H, 4.0; N, 4.28. found C, 77.10; H, 4.24; N, 4.29; ESI-MS (M+1)
328.2
2-(3,5-Dimethoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one (2o): white
solid; m.p. 174-176 °C; IR (KBr) 2972, 1752, 1603, 1568, 1478, 1301,
1178, 1025, 832, 783 cm-1 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 6.8
Hz, 1.2 Hz, 1H), 7.81-7.85 (m, 1H), 7.72 (t, J = 7.2 Hz, 1H), 7.51-7.54 (m,
1H), 7.47 (d, J = 2.0 Hz, 2H), 6.67 (t, J = 2.4 Hz, 1H), 3.89 (s, 6H); 13C
NMR (100 MHz, DMSO-d6): δ 161.2, 159.2, 156.4, 146.5, 137.4, 132.4,
129.2, 128.5, 127.4, 117.4, 105.9, 105.3, 56.1; Anal. Calcd. for
C16H13NO4: C, 67.84; H, 4.63; N, 4.94. found C, 67.79; H, 4.69; N, 4.91;
ESI-MS (M+1) 284.2
2-(3-Methylphenyl)-4H-benzo[d][1,3]oxazin-4-one (2i):[12] White solid;
m.p. 108-110 oC; IR (KBr) 1747, 1607, 1578, 1495, 1446, 1307, 836, 686
cm-1; 1H NMR (400 MHz, CDCl3) δ 8.25 (dd, J = 7.88 Hz, 1.12 Hz, 1H),
8.12 (t, J = 6.2 Hz, 2H), 7.81-7.86 (m, 1H), 7.7 (d, J = 7.96 Hz, 1H), 7.50-
7.54 (m, 1H), 7.41 (t, J = 6.04 Hz, 2H), 2.46 (s, 3H), 13C NMR (100 MHz,
CDCl3): δ 159.7, 157.4, 147.1, 138.7, 136.6, 133.6, 130.2, 128.8, 128.7,
128.6, 128.2, 127.3, 125.6, 117.1, 21.4; Anal. Calcd. for C15H11NO2: C,
75.94; H, 4.67; N, 5.90. found C, 75.86; H, 4.61; N, 5.81; ESI-MS (M+1)
238.2
2-(3,4,5-Trimethoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one
(2p):[11]
white solid; m.p. 178-180 oC; IR (KBr) 2974, 1755, 1605, 1566, 1475,
1303, 1175, 1027, 832, 785 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J
= 7.88 Hz, 1H), 7.81-7.86 (m, 1H), 7.7 (d, J = 7.96 Hz, 1H), 7.50-7.57 (m,
3H), 3.99 (s, 6H), 3.92 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 159.7,
156.9, 153.4, 147.1, 142.2, 136.7, 128.7, 128.2, 127.2, 125.3, 116.8,
105.6, 104.8, 61.1, 56.1; Anal. Calcd. for C17H15NO5: C, 65.17; H, 4.83; N,
4.47. found C, 65.09; H, 4.94; N, 4.41; ESI-MS (M+1) 314.2
2-(3-Methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one (2j):[10a]
White
solid; m.p. 114-116 oC; IR (KBr) 2971, 1604, 1567, 1506, 1305, 1285,
1176, 1047, 831, 781 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.17-8.19 (m,
1H), 7.85 (d, J = 7.8 Hz, 1H), 7.74-7.79 (m, 2H), 7.63 (d, J = 8.04 Hz, 1H),
7.46 (t, J = 7.24 Hz, 1H), 7.35 (t, J = 7.96 Hz, 1H), 7.04-7.07 (m, 1H), 3.8
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.0, 159.6, 157.1, 147.0, 136.7,
131.6, 129.9, 128.7, 128.4, 127.4, 121.0, 119.5, 117.1, 112.7, 55.7; Anal.
Calcd. for C15H11NO3: C, 71.14; H, 4.38; N, 5.53. found C, 71.48; H, 4.21;
N, 5.69; ESI-MS (M+1) 254.2
2-(Thiophen-2-yl)-4H-benzo[d][1,3]oxazin-4-one (2q):[12] White solid;
m.p. 128-130 oC; IR (KBr) 1775, 1619, 1600, 1473, 1424, 1221, 1026,
777, 716 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.22 (d, 7.88 Hz, 1H), 7.97
(d, J = 2.92 Hz, 1H), 7.79-7.83 (m, 1H), 7.61-7.65 (m, 2H), 7.49 (t, J =
7.28 Hz, 1H), 7.18 (t, J = 4.68 Hz, 1H), 13C NMR (100 MHz, CDCl3): δ
2-(3-Fluorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2k):[9] White solid;
m.p. 138-142 oC; IR (KBr) 1759, 1607, 1588, 1446, 1325, 1278, 1008,
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10.1002/ejoc.201700176
European Journal of Organic Chemistry
FULL PAPER
158.9, 153.7, 147.1, 136.6, 134.2, 132.3, 131.7, 128.7, 128.3, 127.9,
126.8, 116.7; Anal. Calcd. for C12H7NO2S: C, 62.87; H, 3.08; N, 6.11; S,
13.99. found C, 62.82; H, 3.01; N, 6.17; S, 13.88; ESI-MS (M+1) 230.2
1021, 835, 763 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 7.6 Hz,
1H), 8.02 (d, J = 8.4 Hz, 2H), 7.81-7.88 (m, 3H), 7.68 (d, J = 8.0 Hz, 1H),
7.53 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ 159.1, 156.4,
146.5, 138.4, 137.3, 130.1, 129.9, 129.2, 128.5, 127.4, 117.4, 101.3;
Anal. Calcd. for C14H8INO2: C, 48.16; H, 2.31; N, 4.01. found C, 48.11; H,
2.29; N, 4.05; ESI-MS (M+1) 350.1
2-(Naphthalen-1-yl)-4H-3,1-benzoxazin-4-one (2r):[11] Yellow solid; m.p.
118-120 °C; IR (KBr) 1755, 1609, 1563, 1395, 1272, 1095, 1048, 1019,
758, 696, 684 cm-1; 1H NMR (400 MHz, DMSO- d6) δ 8.97 (d, J = 8.4 Hz,
1H), 8.19 (d, J = 7.6 Hz, 3H), 8.05 (d, J = 8 Hz, 1H), 7.98 (t, J = 7.2 Hz,
1H), 7.78 (d, J = 8.0 Hz, 1H), 7.60-7.7 (m, 4H); 13C NMR (100 MHz,
CDCl3): δ 159.6, 157.6, 146.8, 134.0, 133.1, 130.7, 130.0, 128.8, 128.5,
127.8, 127.4, 126.9, 126.4, 125.8, 124.8, 116.9; Anal. Calcd. for
C18H11NO2: C, 79.11; H, 4.06; N, 5.13. found C, 79.19; H, 4.12; N, 5.18;
ESI-MS (M+1) 274.2
2-Butyramidobenzoic acid (3a): White solid; m.p. 116-118 oC; 1H NMR
(400 MHz, DMSO-d6) δ 13.53 (s, 1H), 11.09 (s, 1H) 8.48 (d, J = 8.4 Hz,
1H), 7.95 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.11 (t, J = 7.2 Hz,
1H), 2.34 (t, J = 7.6Hz, 2H), 1.58-1.67 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H);
13C NMR (100 MHz, DMSO-d6): δ 171.6, 169.9, 141.4, 134.5, 131.5,
122.9, 120.3, 116.8, 18.7, 13.9; ESI-MS (M+1) 208.1
5-Bromo-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2s): White solid;
m.p. 172-174 °C; IR (KBr) 1753, 1615, 1578, 1496, 1299, 1256, 1059,
838, 776, 685 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.6 Hz, 2H),
7.75 (d, J = 7.6 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.56-7.60 (m, 2H),
7.50-7.54 (m, 2H); 13C NMR (100 MHz, CDCl3): δ 157.6, 156.37, 149.3,
136.0, 134.4, 132.9, 129.7, 128.7, 128.4, 126.9, 123.5, 116.1; Anal.
Calcd. for C14H8BrNO2: C, 55.66; H, 2.67; N, 4.64. found C, 55.59; H,
2.65; N, 4.67; ESI-MS (M+1) 302.2
2-(Cyclohexanecarboxamido)benzoic acid (3b): White solid; m.p. 176-
178 oC; 1H NMR (400 MHz, DMSO-d6) δ 13.52 (s, 1H), 11.17 (s, 1H) 8.50
(d, J = 8.0 Hz, 1H), 7.96 (dd, J = 7.6 Hz, J = 1.6 Hz, 1H), 7.52-7.56(m,
1H), 7.11 (t, J = 7.2 Hz, 1H), 2.25-2.30 (m, 1H), 1.87-1.90 (m, 2H), 1.71-
1.74 (m, 2H), 1.61-1.64 (m, 1H), 1.15-1.45 (m, 5H); 13C NMR (100 MHz,
DMSO-d6): δ 174.5, 170.0, 141.6, 134.4, 131.5, 122.8, 120.3, 116.8, 46.3,
29.5, 25.8, 25.5; ESI-MS (M+1) 248.1
2-[(Phenylcarbonyl)amino]benzoic acid (3c): White solid; 1H NMR
(400 MHz, DMSO-d6) δ 13.89 (s, 1H), 12.15 (s, 1H) 8.69 (d, J = 8.4 Hz,
1H), 8.04 (d, J = 7.6 Hz, 1H), 7.94 (d, J = 7.2 Hz, 2H), 7.55-7.67 (m, 4H),
7.19 (t, J = 7.6 Hz, 1H); 13C NMR (100 MHz, DMSO-d6): δ 170.4, 165.1,
141.5, 135.0, 134.7, 132.5, 131.7, 129.6, 129.4, 128.9, 127.4, 123.3,
120.3, 116.9; ESI-MS (M+1) 242.1
6-Fluoro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2t):[11] White solid;
m.p. 138-140 °C; IR (KBr) 1752, 1625, 1578, 1495, 1297, 1054,1040,
841, 773, 685 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 7.6 Hz, 2H),
7.89 (dd, J = 7.6 Hz, J = 3.2 Hz, 1H), 7.72 (dd, J = 8.8 Hz, J = 4.8 Hz,
1H), 7.50-7.60 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 161.3 (d, J =
249.5 Hz), 158.72 (d, J = 3.1 Hz), 143.5 (d, J = 2.3 Hz), 132.6, 129.9,
129.5 (d, J = 8.5 Hz), 128.7, 128.3, 124.6 (d, J = 24.1Hz), 118.2, 113.8 (d,
J = 24.0 Hz); Anal. Calcd. for C14H8FNO2: C, 69.71; H, 3.34; N, 5.81
found C, 69.69; H, 3.37; N, 5.78; ESI-MS (M+1) 242.2
Acknowledgements
The authors thank Orchid Chemicals and Pharmaceuticals Ltd.
for providing all the necessary facilities Dr. Sridharan Rajagopal
for his technical comments.
7-Methoxy-2-(4-(fluoro)phenyl)-4H-benzo[d][1,3]oxazin-4-one
(2u):
White solid; m.p. 182-186 oC; IR (KBr) 1754, 1626, 1576, 1494, 1295,
1053, 843, 775, 685 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.31 (q, J = 5.2
Hz, 2H), 8.13 (d, J = 8.4 Hz, 1H), 7.19 (t, J = 8.4 Hz, 2H),3.96 (s, 3H),
7.06 (t, J = 5.2 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 166.8, 166.53 (d,
J = 203.0 Hz ), 158.9, 157.0, 149.3, 130.5, 128.7, 126.5(d, J = 3.1 Hz),
117.2, 116.0, 115.8, 109.6, 108.7, 55.8; Anal. Calcd. for C15H10FNO3: C,
66.42; H, 3.72; N, 5.16. found C, 66.48; H, 3.79; N, 5.1; ESI-MS (M+1)
272.2
Keywords: 4H-Benzoxazin-4-ones • Decarboxylative O-
acylation • -Oxocarboxylic acid • N-Aroyl isatin • One pot
reaction
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(2v):[4e] White solid; m.p. 142-144 oC; IR (KBr) 1753, 1627, 1579, 1497,
1298, 1045, 841, 773, 685 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J =
2.0 Hz, 1H), 8.21 (d, J = 8.8 Hz, 2H), 7.89 (dd, J = 8.4 Hz, J = 2.0 Hz,
1H), 7.57(s, 1H), 7.53(t, J = 5.6 Hz, 2H), 1.36 (s, 9H); 13C NMR (100 MHz,
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2-(4-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2y):[12] White solid;
m.p. 188-190 oC; IR (KBr) 1769, 1624, 1603, 1489, 1403, 1323, 1259,
1223, 1095, 1058, 1024, 838, 761 cm-1; 1H NMR (400 MHz, CDCl3) δ
8.24-8.27 (m, 3H), 7.83 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.48-
7.55 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 159.2, 156.2, 146.7, 139.1,
136.6, 129.6, 129.1, 128.7, 128.6, 128.4, 127.2, 116.9; Anal. Calcd. for
C14H8ClNO2: C, 65.26; H, 3.13; N, 5.44. found C, 65.19; H, 3.11; N, 5.47;
ESI-MS (M+1) 258.2
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2-(4-Iodophenyl)-4H-benzo[d][1,3]oxazin-4-one (2z): White solid; m.p.
168-170 oC; IR (KBr) 1765, 1621, 1605, 1485, 1321, 1257, 1224, 1056,
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10.1002/ejoc.201700176
European Journal of Organic Chemistry
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10.1002/ejoc.201700176
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
One pot fashion
Key Topic*
O
K. Bharathimohan, T. Ponpandian, Jafar
A. Ahamed*
O
N
O
Ag2O (1 eq.)
O
K2S2O8 (1 eq.)
O
NH
O
N
OH
Acetonitrile
R1
R1
Ar
R2
Page No. – Page No.
O
R2
Reflux
O
R1
Title
24 examples
upto 92%
Silver mediated synthesis of 4H-
benzoxazin-4-ones by intramolecular
decarboxylative O-acylation reaction
with α-oxocarboxylic acid
R2
.
.
Inexpensive Ag salt
Scalable to gram scale .
.
Shorter reaction time
Wide substrate scope
* First report of intramoleculer decarboxylative acylation and more convenient method to prepare 4H-benzoxazin-4-ones.
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