One-Pot Synthesis of 2-Arylbenzoxazinones from 2-Arylindoles with (Diacetoxyiodo)benzene as the Sole Oxidant

Article abstract of DOI:10.1055/s-0036-1590933

A series of synthetically interesting 2-arylbenzoxazinones was prepared from 2-arylindoles by an efficient oxidative reaction mediated by (diacetoxyiodo)benzene [PhI(OAc) ₂ ] and assisted by water. PhI(OAc) ₂ was used as the sole oxi

Full text of DOI:10.1055/s-0036-1590933

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–G
paper
A
en
X.-X. Shang et al.
Paper
Synthesis
One-Pot Synthesis of 2-Arylbenzoxazinones from 2-Arylindoles
with (Diacetoxyiodo)benzene as the Sole Oxidant
Xian-Xing Shang
Huu-Manh Vu
Xu-Qin Li*
O
O
PhI(OAc)2, H2O
R
R
Ar
DMF, 60 °C, air
N
X
N
Ar
X
H
School of Chemical and Biological Engineering, University of
Science and Technology Beijing, 30 Xueyuan Road, Haidian
District, Beijing 100083, P. R. of China
22 examples
yield: 31–75%
X = CH, N
- water-assisted
- metal-free
lixuqin@ustb.edu.cn
- broad substrate scope
Received: 12.07.2017
Accepted after revision: 15.09.2017
Published online: 19.10.2017
tantly, 2-substituted 4H-3,1-benzoxazin-4-ones are also
versatile building blocks for the synthesis of pharmaceuti-
cally active compounds. An example is compound V, an
anticonvulsant agent, which can be synthesized from 2-
phenyl-4H-3,1-benzoxazin-4-one (2a) in two steps (Scheme
1).4 Due to its synthetic importance, the development of ap-
proaches toward the preparation of 4H-3,1-benzoxazin-4-
one derivatives has received considerable attention in or-
ganic synthesis.
The traditional synthesis of benzoxazinones is by cy-
clization of substituted anthranilic acids, for which corro-
sive and toxic acyl chlorides are inevitably required.4 More
recently, transition-metal-catalyzed carbonylation of o-
haloanilines,5 benzanilides,6 and aryl urea derivatives7 has
been reported to give benzoxazinones, in which carbon
monoxide is used as the carbonyl source. Additionally,
palladium-catalyzed cleavage of the C–C triple bond in 2-
azidoalkynylbenzenes was found to be an alternative route
for the synthesis of benzoxazinones.8 Copper-catalyzed
cyclization of N-acyl-2-halobenzamides was also disclosed
to yield a variety of benzoxazinones.9 Recently, oxidative
DOI: 10.1055/s-0036-1590933; Art ID: ss-2017-h0453-op
Abstract A series of synthetically interesting 2-arylbenzoxazinones
was prepared from 2-arylindoles by an efficient oxidative reaction me-
diated by (diacetoxyiodo)benzene [PhI(OAc)2] and assisted by water.
PhI(OAc)2 was used as the sole oxidant and water was a crucial additive.
Our preliminary mechanistic investigations suggest that a water-in-
volved, iodine(III)-promoted sequential oxidation of 2-arylindoles,
which was terminated by an interesting Grob-type fragmentation of a
fused tricyclic precursor, might be the main components of this one-
pot transformation.
Key words benzoxazinones, hypervalent iodine, indoles, oxidation,
water-assisted
The 4H-3,1-benzoxazin-4-one core is an important
structural skeleton found in many bioactive compounds
and pharmaceutical drugs (Figure 1). For example, I has the
ability to lower the level of plasma cholesterol and tri-
glycerides,1 II and III show good cytotoxicity against P338
cells,2 and IV acts as a serine hydrolase inhibitor.3 Impor-
O
N
O
N
R
O2N
O
O
O
O
N
N
O
N
N
I R = Br
II R = Me
III
IV
Figure 1 Some bioactive molecules with the 4H-3,1-benzoxazin-4-one core
O
O
HN
O
O
N
O
N
NH2
Ph
NH2NH2•H2O
O
N
H
O
N
N
N
N
Ph
Ph
V
2a
Scheme 1 Using benzoxazinone in the synthesis of the anticonvulsant quinazolinone V
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

B
X.-X. Shang et al.
Paper
Synthesis
tandem cyclization of N-TFA-protected 2-alkynylanilines
was revealed to afford 2-arylbenzoxazinones.10
3). The amount of PhI(OAc)2 as oxidant was also examined
in this model (entries 6–8), and it was found that at least
four equivalents of PhI(OAc)2 were required for a better
conversion of 1a to 2a (entry 7). Additionally, some basic
and acidic additives (entries 9, 10) were also added to the
current model reaction, but no positive results were ob-
served. Interestingly, a significant improvement of reaction
yield was achieved when three equivalents of H2O were
added to the model reaction (entry 11). Following further
examination on the quantities of H2O (entries 12–14), an
optimal yield of 71% could be obtained with 10 to 15
equivalents of H2O (entries 13, 14). Compared with DMF as
In addition to the above-mentioned 1,2-disubstituted
benzene derivatives as substrates, interestingly, substituted
indoles A as starting materials were also investigated in the
synthesis of benzoxazinones B. As shown in Scheme 2, the
synthesis of 2-arylbenzoxazinones could be alternatively
accessed from 2-arylindoles by Oxone-mediated oxidation11
or a copper-catalyzed aerobic oxidative tandem reaction.12
It has also been reported that visible-light photocatalytic
aerobic oxygenation of indoles could afford a few examples
of benzoxazinones.13 To the best of our knowledge, howev-
er, the one-pot synthesis of 2-arylbenzoxazinones by a hy-
pervalent iodine(III)-mediated oxidative reaction of 2-
arylindoles has not yet been reported (Scheme 2).
Table 1 Optimization of Reaction Conditionsa
O
Ac2O
CuCl (cat.), Na2CO3
PhI(OAc)2, additive
O
Yamashita
(2014)
solvent
under air
O2 (1 atm)
DMSO, 80 °C
N
H
N
O
1a
2a
Oxone
O
Guan
(2013)
R1
R1
R2 CH3NO2
100 °C
Entry
Equiv of PhI Solvent
(OAc)2
Additive
(equiv)
Temp
(°C)
Yieldb
(%)
N
H
N
R2
A
B
1
2
3
3
3
3
3
2
4
5
4
4
4
4
4
4
4
4
4
4
4
4
DMFc
DMFc
DMFc
DMFc
DMFc
DMFc
DMFc
DMFc
DMF
–
100
80
60
40
0
13
15
19
16
traced
10
20
20
0
2-arylindoles
2-arylbenzoxazinones
–
hypervalent iodine(III) reagent
this work
3
–
Scheme 2 Synthesis of 2-arylbenzoxazinones from 2-arylindoles
4
–
5
–
The chemistry of hypervalent iodine compounds has ex-
perienced an unprecedented, explosive development in the
past decades.14 The oxidation properties of hypervalent io-
dine(III) compounds resemble those of heavy metal species
[e.g., Hg(III), Tl(III), Pb(IV)], but without the accompanying
toxicity and environmental problems. Generally, hyperva-
lent organic iodine reagents have mild and highly selective
oxidizing properties. Notably, the commercially available
PhI(OAc)2, as one of the most widely used trivalent iodine
reagents, has been used in various kinds of oxidation reac-
tions, such as the oxidation of alcohols or phenols,15 the ox-
idative functionalization of carbonyl compounds and ole-
fins,16 oxidative rearrangement and fragmentation reac-
tions,17 free-radical cyclization reactions,18 and oxidative
coupling of electron-rich aromatics.19 In connection to our
interest in hypervalent iodine chemistry, we recently devel-
oped a novel method for the straightforward synthesis of 2-
arylbenzoxazinone derivatives from 2-arylindoles by using
PhI(OAc)2 as the sole oxidant. Herein, we report our prelim-
inary results.
6
–
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
7
–
8
–
9
basee (3)
acidf (3)
H2O (3)
H2O (6)
H2O (10)
H2O (15)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
H2O (10)
10
11
12
13
14
15
16
17
18
19
20
DMF
0–14
57
68
71
71
52
0
DMF
DMF
DMF
DMF
DMA
DMSO
MeCN
THF
9
42
33
20
EtOAc
toluene
a Reaction conditions: 1a (1.0 mmol), PhI(OAc)2, additive, solvent (10 mL),
under air, 24 h.
b Isolated yield.
Initially, the hypervalent iodine mediated oxidative re-
action was investigated in DMF under air at 100 °C by using
2-arylindole 1a as substrate and PhI(OAc)2 as oxidant, and
the desired benzoxazinone product 2a could be obtained,
but in a low yield of 13% (Table 1, entry 1). By varying the
reaction temperature from 40 °C to 100 °C (entries 1–5),
the reaction yield could be slightly improved at 60 °C (entry
c This reaction was conducted under air, and therefore introducing some
water to the reaction system could not be avoided as DMF is moisture-
sensitive in air.
d The oxidative side product, 2-phenyl-3H-indol-3-one (3a), was isolated in
8% yield.
e No desired product could be isolated when a base (e.g., Na2CO3, NaHCO3,
NaOH, Et3N, pyridine, DMAP) was used as additive.
f The following acids were investigated (product yield given in parenthe-
ses): TFA (5%), AcOH (14%), TsOH·H2O (0%).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

C
X.-X. Shang et al.
Paper
Synthesis
solvent (entry 13), a further screening of a series of solvents
was also conducted (entries 15–20), but solvents other than
DMF gave inferior results in terms of chemical yield.
Considering the different oxidation properties of hyper-
valent iodine reagents, a variety of iodine(III) oxidants with
different oxy ligands [e.g., PhI(OCOCF3)2, PhI(OPiv)2,
PhI(OCOPh)2, PhIO, PhI(OH)OTs, iodosodilactone20] were
used instead of PhI(OAc)2 (Table 2, entries 1–6), but a nega-
tive influence on the reaction yield was observed in these
cases.
phenyl-4H-benzo[d][1,3]oxazin-4-one (2f), obtained in 31%
yield by our protocol, could only be afforded in a trace
amount by Yamashita’s method.12 Both the 7- and 8-substi-
tuted indoles 1g,h showed similar reactivity to that of the
aforementioned 6-substituted indoles. In addition, 2-phe-
nyl-1H-pyrrolo[2,3-b]pyridine (1i) was also tested under
the optimized conditions, giving the expected 2-phenyl-
4H-pyrido[2,3-d][1,3]oxazin-4-one (2i) in moderate yield.
Importantly, functionalized benzoxazinone 2j, a biological-
ly interesting substance,1 could be readily obtained in 60%
yield.
Table 2 Optimization of the Iodine Reagenta
O
PhI(OAc)2 (4 equiv)
4
5
O
5
H2O (10 equiv)
6
2
O
Ar
R
R
DMF, 60 °C
under air, 24 h
O
6
N
iodine reagent
X
7
Ar
2
X
N
H
N
H2O, DMF, 60 °C
1
2
N
H
X = CH, N
O
1a
2a
O
O
O
N
O
O
O
O
R
O
I
O
OH
O
N
O
I
I
O
7
O
O
O
O
Ph
Me
Ph
N
Ph
O
8
Cl
O
2a (R = H), 71%
O
O
2g, 59%
2h, 46%
2b (R = Me), 67%
2c (R = F), 50%
2d (R = Cl), 59%
2e (R = Br), 61%
2f (R = NO2), 31%
iodosodilactone
DMP
IBX
O
O
O
Entry
Iodine reagent
Yieldb (%)
Br
O
1
2
PhI(OCOCF3)2
PhI(OPiv)2
11
21
26
38
0
N
N
Ph
N
O
O
N
2i, 40%
2j, 60%
t-Bu
3
PhI(OCOPh)2
PhIO
4
O
O
R1
5
PhI(OH)OTs
iodosodilactone
4-FC6H4I(OAc)2
O
O
2k (R1 = Me), 66%
2l (R1 = F), 58%
2m (R1 = Cl), 65%
2n (R1 = Br), 69%
2o (R1 = CF3), 75%
2p (R1 = Ph), 53%
OMe
Me
Me
6
23
64
63
0
N
N
7
8
4-MeOC6H4I(OAc)2
2q, 62%
2r, 64%
9
IBX
O
O
10
DMP
0
O
N
O
O
O
N
a Reaction conditions: 1a (1.0 mmol), iodine reagent (4 equiv), H2O
(10 equiv), DMF (10 mL), 60 °C, under air, 24 h.
b Isolated yield.
O
O
N
N
N
N
N
N
N
2s, 50%
2t, 64%
2u, 0%
2v, 0%
To probe the electronic effect of the aryl substituent in
the analogues of PhI(OAc)2, 4-(diacetoxyiodo)fluoroben-
zene (Table 2, entry 7) and 4-(diacetoxyiodo)anisole17 (en-
try 8) were then tested, showing positive reactivity with
slightly reduced yields. Two iodine(V) reagents, IBX and
DMP (entries 9 and 10), were also examined as oxidants,
but the expected 2-arylbenzoxazinone 2a was not isolated.
After the above optimization of the reaction conditions,
the scope and generality of this reaction were then investi-
gated (Scheme 3). A series of 2-phenylindoles 1a–f with
electronically different substituents (R = H, Me, F, Cl, Br,
NO2) were firstly used as substrates, and the desired 2-
phenylbenzoxazinones 2a–f could be achieved in reason-
able to moderate yields. It should be noted that 6-nitro-2-
Scheme 3 Oxidation of 2-arylindoles 1 for the synthesis of 2-aryl-
benzoxazinones 2 by using PhI(OAc)2. Reagents and conditions: 1 (1.0
mmol), PhI(OAc)2 (4.0 equiv), H2O (10 equiv), DMF (10 mL), 60 °C, 24 h,
under air; isolated yields are given.
Subsequently, the influence of the C-2 aryl group in in-
doles 1 was then examined. As shown in Scheme 3, various
2-arylindoles 1k–r bearing electron-donating and electron-
withdrawing groups on the C-2 aryl ring were employed
under the developed reaction conditions, and the corre-
sponding benzoxazinones 2k–r could be obtained smoothly
in moderate yields. Additionally, two examples using 1s,t
with C-2 heteroaromatic substituents were also investigat-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

D
X.-X. Shang et al.
Paper
Synthesis
ed, successfully giving the corresponding pyridyl-contain-
ing products 2s and 2t. However, from 2-(2-pyridyl)-1H-in-
dole (1u) and 2-(1H-pyrazol-1-yl)-1H-indole (1v) as sub-
strates under the present oxidation reaction conditions,
surprisingly no desired products could be isolated, showing
the negative influence of ortho heteroaryl substituents on
the formation of the desired benzoxazinones.
quently, hydrolysis of the enol ester group in B gave 2-phe-
nyl-3-oxindole C and its enol tautomer C′,22 which could be
further oxidized via the iodine(III) species D to afford 2-
phenyl-3H-indol-3-one (3a). After nucleophilic attack of
water on the carbonyl group in 3a and ligand exchange of
PhI(OAc)2 with the imino group in 3a, a novel Grob-type
fragmentation,23 chemically initiated by the higher oxida-
tion state of the iodine center in E, furnished the final ben-
zoxazinone product 2a with the release of PhI and HOAc.
In summary, a novel water-assisted, PhI(OAc)2-mediated
oxidative reaction has been developed, providing an alter-
native method for the one-pot synthesis of various 2-aryl-
benzoxazinones starting from readily available 2-arylin-
doles. This reaction has a wide functional group tolerance,
and is characterized by the employment of PhI(OAc)2 as the
sole oxidant and the presence of water as a crucial additive.
Preliminary mechanistic investigations suggest that a wa-
ter-involved, iodine(III)-promoted sequential oxidation of
2-arylindoles, terminated by an interesting Grob-type frag-
Several control experiments were conducted in order to
develop a plausible mechanism for this reaction (Scheme
4). Compared with the results when using 1a under our
standard conditions (Table 1, entry 13, 71% yield), a similar
reaction efficiency for 2a (70% yield) could also be obtained
in the presence of water under nitrogen instead of air
(Scheme 4, a). However, the absence of water in absolute
anhydrous DMF under nitrogen did not result in the forma-
tion of the desired benzoxazinone product 2a (Scheme 4, b),
indicating the essential assisting role of water in the current
iodine(III)-mediated oxidative transformation. Since 2-phe-
nyl-3H-indol-3-one (3a) was obtained as an oxidative side
product in 8% yield during optimization of the reaction con-
ditions (Table 1, entry 5), one additional experiment using
3a was then conducted in the PhI(OAc)2-mediated oxidation
in the presence of water in DMF under nitrogen (Scheme 4,
c). In contrast to the formation of no product from 3a in the
absence of water in anhydrous DMF under nitrogen
(Scheme 4, d), the desired product 2a was obtained in 78%
yield in this case (Scheme 4, c), indicating that 3a might be
involved as an intermediate in this iodine(III)-mediated oxi-
dation reaction.
PhI(OAc)2 (4 equiv)
DMF (anhyd), under N2
60 °C, 24 h
PhI(OAc)2 (2 equiv)
DMF (anhyd), under N2
60 °C, 12 h
b
d
O
O
O
Ph
Ph
N
H
N
N
Ph
3a
1a
2a
a
c
70% yield
78% yield
On the basis of the above studies, a plausible mecha-
nism for this reaction is proposed in Scheme 5, as exempli-
fied by the transformation of 1a to 2a. Initially, electrophilic
attack of PhI(OAc)2 at the C-3 position of indole 1a gave 3-
acetoxy-substituted indole B21 via intermediate A. Subse-
PhI(OAc)2 (4 equiv)
DMF (anhyd), H2O (10 equiv)
60 °C, under N2, 24 h
PhI(OAc)2 (2 equiv)
DMF (anhyd), H2O (5 equiv)
60 °C, under N2, 12 h
Scheme 4 Control experiments for preliminary mechanistic studies
Ph
OAc
Ph
OAc
I
AcO
I
OAc
Ph
PhI(OAc)2
AcO
Ph
Ph
– HOAc
– PhI
N
N
Ph
H
H
N
H
N
A
B
1a
H
H2O
– HOAc
OAc
OH
O
O
I
O
Ph
Ph
PhI(OAc)2
– HOAc
Ph
Ph
Ph
– HOAc
– PhI
N
N
N
N
H
H
3a
H
D
C'
C
(enol form)
(keto form)
H
H
O
O
N
O
H
O
O
PhI(OAc)2
H2O
O
Ph
Ph
N
– HOAc
– HOAc
– PhI
N
Ph
I
OAc
AcO
I
OAc
Ph
2a
Ph
E
Scheme 5 Proposed mechanism for the water-assisted, PhI(OAc)2-mediated oxidative reaction
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

E
X.-X. Shang et al.
Paper
Synthesis
mentation of a fused tricyclic precursor, might be involved
in this reaction. The current water-assisted, iodine(III)-me-
diated oxidative reaction not only expands the application
of hypervalent iodine chemistry, but also enriches the syn-
thetic chemistry of the 4H-3,1-benzoxazin-4-one core
structure based on the oxidation chemistry of indoles.
6-Nitro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2f)8
Yield: 120 mg (31%); yellow needles; mp 157–158 °C.
1H NMR (400 MHz, CDCl3): δ = 9.17 (s, 1 H), 8.33 (d, J = 8.0 Hz, 2 H),
8.21–8.18 (dd, J = 8.0, 2.0 Hz, 1 H), 7.91 (d, J = 9.6 Hz, 1 H), 7.74–7.71
(t, J = 7.2 Hz, 1 H), 7.63–7.59 (t, J = 8.0 Hz, 2 H).
ESI-MS: m/z [M + H]+ calcd for C14H8N2O4: 269.05; found: 269.11.
7-Methyl-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2g)11
Yield: 140 mg (59%); colorless needles; mp 159–160 °C.
1H NMR (400 MHz, CDCl3): δ = 8.29 (d, J = 7.6 Hz, 2 H), 8.11 (d, J = 8.0
Hz, 1 H), 7.57–7.47 (m, 4 H), 7.31 (d, J = 8 Hz, 1 H), 2.49 (s, 3 H).
Chemicals and reagents were purchased from commercial suppliers
and used as received. 1H NMR spectra (400 MHz) were obtained from
samples in CDCl3, unless noted otherwise. The chemical shift values
are given relative to internal TMS. Unless noted otherwise, the purifi-
cation was performed by using column chromatography on silica gel.
ESI-MS: m/z [M + H]+ calcd for C15H11NO2: 238.08; found: 238.10.
8-Chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2h)11
4H-Benzo[d][1,3]oxazin-4-ones 2; General Procedure
Yield: 118 mg (46%); colorless needles; mp 172–173 °C.
A mixture of 1 (1.0 mmol), PhI(OAc)2 (1.288 g, 4.0 mmol), and H2O
(180 μL, 10 mmol) in DMF (10 mL) was stirred at 60 °C under air for
24 h, and then the mixture was cooled to r.t. The mixture was
quenched with H2O (30 mL) and extracted with EtOAc. The organic
extracts were washed with brine, dried over Na2SO4, and then con-
centrated under reduced pressure. The crude product was purified by
column chromatography (silica gel, PE–EtOAc) to give the correspond-
ing product 2.
1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 8.0 Hz, 2 H), 8.15 (d, J = 8.0
Hz, 1 H), 7.88 (d, J = 8.0 Hz, 1 H), 7.60–7.56 (t, J = 7.2 Hz, 1 H), 7.52–
7.49 (m, 2 H), 7.43–7.39 (m, 1 H).
ESI-MS: m/z [M + H]+ calcd for C14H8ClNO2: 258.02; found: 258.06.
2-Phenyl-4H-pyrido[2,3-d][1,3]oxazin-4-one (2i)24
Yield: 89 mg (40%); yellow needles; mp 130–131 °C.
1H NMR (400 MHz, CDCl3): δ = 8.90 (s, 1 H), 8.53 (d, J = 8.04 Hz, 1 H),
8.32 (d, J = 7.6 Hz, 2 H), 7.71–7.67 (t, J = 7.2 Hz, 1 H), 7.60–7.56 (t, J =
7.6 Hz, 2 H), 7.27–7.24 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 181.0 (CH), 165.5 (C), 161.9 (C), 158.6
(C), 135.2 (CH), 134.4 (CH), 131.4 (C), 130.3 (CH), 128.9 (CH), 132.8
(CH), 114.8 (C).
2-Phenyl-4H-benzo[d][1,3]oxazin-4-one (2a)11
Yield: 158 mg (71%); colorless needles; mp 113–114 °C.
1H NMR (400 MHz, CDCl3): δ = 8.32 (d, J = 8.0 Hz, 2 H), 8.25 (d, J = 8.0
Hz, 1 H), 7.84–7.80 (t, J = 7.6 Hz, 1 H), 7.70 (d, J = 8.0 Hz, 1 H), 7.52–
7.49 (m, 4 H).
ESI-MS: m/z for C14H9NO2: 224.06; found: 224.06.
ESI-MS: m/z [M + H]+ calcd for C13H8N2O2: 225.06; found: 225.1.
6-Methyl-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2b)11
6-Bromo-2-(4-tert-butylphenyl)-4H-benzo[d][1,3]oxazin-4-one
Yield: 159 mg (67%); colorless needles; mp 139–140 °C.
1H NMR (400 MHz, CDCl3): δ = 8.28 (d, J = 7.6 Hz, 2 H), 8.01 (s, 1 H),
7.62–7.46 (m, 5 H), 2.47 (s, 3 H).
ESI-MS: m/z [M + H]+ calcd for C15H11NO2: 238.08; found: 238.10.
(2j)1
Yield: 215 mg (60%); colorless needles; mp 131–133 °C.
1H NMR (400 MHz, CDCl3): δ = 8.33 (s, 1 H), 8.20 (d, J = 8.0 Hz, 2 H),
7.88 (dd, J = 8.4 Hz, 1 H), 7.55–7.49 (m, 3 H), 1.35 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 158.4 (C), 157.6 (C), 156.8 (C), 146.1
(C), 139.6 (CH), 131.0 (CH), 128.8 (CH), 128.2 (CH), 127.0 (CH), 125.8
(CH), 121.1 (CH), 118.3 (CH), 35.2 (CH), 31.1 (CH3).
6-Fluoro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2c)11
Yield: 120 mg (50%); colorless needles; mp 131–132 °C.
1H NMR (400 MHz, CDCl3): δ = 8.28 (d, J = 7.2 Hz, 2 H), 7.88–7.85 (m, 1
ESI-MS: m/z [M + H]+ calcd for C18H16BrNO2: 358.04; found: 358.4.
H), 7.69–7.67 (m, 1 H), 7.56–7.48 (m, 4 H).
2-(p-Tolyl)-4H-benzo[d][1,3]oxazin-4-one (2k)10
ESI-MS: m/z [M + H]+ calcd for C14H8FNO2: 242.05; found: 242.10.
Yield: 156 mg (66%); colorless needles; mp 144–145 °C.
6-Chloro-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2d)11
1H NMR (400 MHz, CDCl3): δ = 8.22–8.17 (m, 3 H), 8.81–8.77 (t, J = 7.6
Hz, 1 H), 7.66 (d, J = 8 Hz, 1 H), 7.49–7.46 (t, J = 7.6 Hz, 1 H), 7.30 (d, J =
8.0 Hz, 2 H), 2.42 (s, 3 H).
Yield: 152 mg (59%); colorless needles; mp 188–189 °C.
1H NMR (400 MHz, CDCl3): δ = 8.29 (d, J = 7.2 Hz, 2 H), 8.17 (s, 1 H),
7.76–7.48 (m, 4 H), 7.52 (t, J = 8.0 Hz, 1 H).
ESI-MS: m/z [M + H]+ calcd for C15H11NO2: 238.08; found: 238.12.
ESI-MS: m/z [M + H]+ calcd for C14H8ClNO2: 258.02; found: 258.10.
2-(4-Fluorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2l)11
6-Bromo-2-phenyl-4H-benzo[d][1,3]oxazin-4-one (2e)11
Yield: 140 mg (58%); colorless needles; mp 124–125 °C.
1H NMR (400 MHz, CDCl3): δ = 8.32–8.28 (m, 2 H), 8.23 (d, J = 8.0 Hz, 1
H), 7.82–7.79 (t, J = 8.0 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 1 H), 7.51–7.48 (t,
J = 7.6 Hz, 1 H), 7.19–7.15 (t, J = 8.4 Hz, 2 H).
Yield: 184 mg (61%); colorless needles; mp 189–190 °C.
1H NMR (400 MHz, CDCl3): δ = 8.34 (s, 1 H), 8.28 (d, J = 7.2 Hz, 2 H),
7.90 (d, J = 8.2 Hz, 1 H), 7.57–7.47 (m, 4 H).
ESI-MS: m/z [M + H]+ calcd for C14H8FNO2: 242.05; found: 242.08.
ESI-MS: m/z [M + H]+ calcd for C14H8BrNO2: 301.97; found: 302.00.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

F
X.-X. Shang et al.
Paper
Synthesis
2-(4-Chlorophenyl)-4H-benzo[d][1,3]oxazin-4-one (2m)11
1H NMR (400 MHz, CDCl3): δ = 9.48 (s, 1 H), 8.77 (d, J = 7.6 Hz, 1 H),
8.53 (d, J = 7.6 Hz, 1 H), 8.24 (d, J = 8.0 Hz, 1 H), 7.85–7.81 (t, J = 8.0 Hz,
1 H), 7.70 (d, J = 8.0 Hz, 1 H), 7.55–7.51 (t, J = 7.6 Hz, 1 H), 7.45–7.42
(dd, J = 8.0, 4.8 Hz, 1 H).
Yield: 167 mg (65%); colorless needles; mp 181–182 °C.
1H NMR (400 MHz, CDCl3): δ = 8.23–8.21 (m, 3 H), 7.83–7.79 (m, 1 H),
7.67 (d, J = 8.0Hz, 1 H), 7.53–7.45 (m, 3 H).
ESI-MS: m/z [M + H]+ calcd for C13H8N2O2: 225.06; found: 225.09.
ESI-MS: m/z [M + H]+ calcd for C14H8ClNO2: 258.02; found: 258.05.
2-Phenyl-3H-indol-3-one (3a)11
2-(4-Bromophenyl)-4H-benzo[d][1,3]oxazin-4-one (2n)11
Yield: 17 mg (8%); red solid; mp 96–97 °C.
1H NMR (400 MHz, CDCl3): δ = 8.36 (d, J = 7.6 Hz, 2 H), 7.54–7.45 (m, 5
H), 7.40 (d, J = 7.6 Hz, 1 H), 7.26 (t, J = 7.6 Hz, 1 H).
Yield: 208 mg (69%); colorless needles; mp 179–180 °C.
1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 7.6 Hz, 1 H), 8.16 (d, J = 8.0
Hz, 2 H), 7.83–7.19 (t, J = 6.8 Hz, 1 H), 7.67–7.62 (m, 3 H), 7.53–7.49 (t,
J = 7.2 Hz, 1 H).
ESI-MS: m/z [M + H]+ calcd for C14H9NO: 208.07; found: 208.05.
ESI-MS: m/z [M + H]+ calcd for C14H8BrNO2: 301.97; found: 302.00.
Funding Information
2-[4-(Trifluoromethyl)phenyl]-4H-benzo[d][1,3]oxazin-4-one
(2o)8
This work was supported by grants from the National Standardization
Project of Traditional Chinese Medicine (No. ZYBZH-Y-JX-27) and Fun-
damental Research Funds for the Central Universities (No. FRF-BR-14-
Yield: 218 mg (75%); colorless needles; mp 90–91 °C.
1H NMR (400 MHz, CDCl3): δ = 8.42 (d, J = 8.4 Hz, 2 H), 8.25 (d, J = 8.0
Hz, 1 H), 7.86–7.82 (t, J = 8 Hz, 1 H), 7.76 (d, J = 8.4, 2 H), 7.71 (d, J = 8
Hz, 1 H), 7.56–7.53 (t, J = 7.6 Hz, 1 H).
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ESI-MS: m/z [M + H]+ calcd for C15H8F3NO2: 292.05; found: 292.09.
Acknowledgment
2-(1,1′-Biphenyl-4-yl)-4H-benzo[d][1,3]oxazin-4-one (2p)11
We thank Prof. Dr. Chun-An Fan from Lanzhou University for helpful
discussions and great suggestions.
Yield: 158 mg (53%); colorless needles; mp 138–139 °C.
1H NMR (400 MHz, CDCl3): δ = 8.37 (d, J = 8.4 Hz, 2 H), 8.23 (d, J = 7.6
Hz, 1 H), 7.84–7.80 (t, J = 8.0 Hz, 1 H), 7.73–7.64 (m, 5 H), 7.52–7.37
(m, 4 H).
Supporting Information
ESI-MS: m/z [M + H]+ calcd for C20H13NO2: 300.09; found: 300.16.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590933.
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2-(3-Methoxyphenyl)-4H-benzo[d][1,3]oxazin-4-one (2q)11
Yield: 157 mg (62%); colorless needles; mp 117–118 °C.
References
1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 8.0 Hz, 1 H), 7.90 (d, J = 7.6
Hz, 1 H), 7.83–7.80 (m, 2 H), 7.69 (d, J = 8.0 Hz, 1 H), 7.52–7.48 (t, J =
7.6 Hz, 1 H), 7.41–7.37 (t, J = 8.0 Hz, 1 H), 7.11–7.09 (dd, J = 0.2, 6.4 Hz,
1 H), 3.89 (s, 3 H).
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2-(3,4-Dimethylphenyl)-4H-benzo[d][1,3]oxazin-4-one (2r)11
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Yield: 112 mg (50%); white solid; mp 161–162 °C.
1H NMR (400 MHz, CDCl3): δ = 8.81 (d, J = 5.2 Hz, 2 H), 8.26 (d, J = 7.6
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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X.-X. Shang et al.
Paper
Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G