Biomass-involved, facile and one-pot synthesis of N-aryl-2(3H)-benzoxazolones from methyl 3-dehydroshikimiate

Article abstract of DOI:10.1039/c4ra08233h

A facile and one-pot method for the synthesis of N-aryl-2(3H)-benzoxazolones via microwave-assisted consecutive reactions between the biomass-derived methyl 3-dehydroshikimiate (3-MDHS), anilines and bis(trichloromethyl) carbonate (BTC) is reported. The protocol includes the efficient generation of the platform compounds N-arylated 2-aminophenols, followed by the smooth annulation reaction induced by BTC. This sequential process represents a metal-free, sustainable and functional group compatible method for the rapid construction of N-aryl-2(3H)-benzoxazolones. This journal is

Full text of DOI:10.1039/c4ra08233h

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Biomass-involved, facile and one-pot synthesis of
N-aryl-2(3H)-benzoxazolones from methyl 3-
dehydroshikimiate†
Cite this: RSC Adv., 2014, 4, 39020
Ensheng Zhang,ad Xuejing Zhang,b Yuchen Cai,b Dejian Wang,ad Tianlong Xu,ad
c
b
ab
*
Jun Li, Ming Yan and Yong Zou
A facile and one-pot method for the synthesis of N-aryl-2(3H)-benzoxazolones via microwave-assisted
consecutive reactions between the biomass-derived methyl 3-dehydroshikimiate (3-MDHS), anilines and
bis(trichloromethyl) carbonate (BTC) is reported. The protocol includes the efficient generation of the
platform compounds N-arylated 2-aminophenols, followed by the smooth annulation reaction induced
by BTC. This sequential process represents a metal-free, sustainable and functional group compatible
method for the rapid construction of N-aryl-2(3H)-benzoxazolones.
Received 2nd July 2014
Accepted 14th August 2014
DOI: 10.1039/c4ra08233h
www.rsc.org/advances
substrates were used in the abovementioned methods. In this
context, an alternative method that is facile, compatible and
Introduction
could make use of biomass-derived feedstock for the assembly
of N-aryl-2(3H)-benzoxazolones would be genuinely attractive
(Scheme 1).
The 2(3H)-benzoxazolone scaffold represents an important
privileged structure ubiquitously found in pharmaceuticals,
agrochemicals and bioactive compounds. For example, the
antipyretic analgesic chlorzoxazone,1 the insecticide and acari-
cide phosalone,2 the PPAR a/g dual agonists3 and the P2X3
receptor antagonist4 are all characterized by the 2(3H)-benzox-
azolone core structure (Fig. 1). Accordingly, considerable efforts
have been devoted to the preparation of 2(3H)-benzoxazolones
and many effective methods have been reported.5 Compared to
the formation of N-unsubstituted 2(3H)-benzoxazolones, the
construction of N-aryl-2(3H)-benzoxazolones is far less explored.
Generally, method for the assembly of N-aryl-2(3H)-benzox-
azolone motif involved the Diels–Alder reaction between exo-2-
oxazolidinone dienes and acrolein followed by dehydrogenation
using DDQ.6 Chen's method based upon the Ullmann coupling
reaction between 2(3H)-benzoxazolones and aryl halide was also
effective and workable4 (Scheme 1). However, these methods
still suffer from multi-step sequences, harsh reaction condi-
tions, long reaction times, as well as the necessity of transition
metal-catalysts and the difficulty in obtaining starting materials
in most cases. In addition, to the best of our knowledge,
petroleum-based starting materials, but not biomass-derived
In the past few years, cyclohexanones, cyclohexenones or
polyhydroxylated cyclohexenones have been demonstrated to be
intriguing precursors for the construction of various aromatics
such as arylamines,7 2-aminobenzothiazoles,8 protocatechuic
acid,9 hydroquinone,10 catechol,11 gallic acid,12 and N-arylated
amino acid derivatives.13 This novel aliphatic to aromatic
strategy is widely applicable due to the thermodynamically
favourable and readily occurred dehydrogenation and/or dehy-
dration process that lead to the formation of aromatics from
cyclohexanone or polyhydroxylated cyclohexanone framework
under mild conditions. Our previous studies have shown that
the abundantly available bio-feedstock shikimic acid could be
easily transformed into methyl 3-dehydroshikimiate (3-MDHS, 1),
aGuangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650,
P. R. China. E-mail: zou_jinan@163.com; Fax: +86 (20)85231119; Tel: +86 (20)
85231309
bSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P. R.
China. E-mail: zou_jinan@163.com
cSecond Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang 310009,
P. R. China
dUniversity of Chinese Academy of Sciences, Beijing 100039, P. R. China
† Electronic supplementary information (ESI) available: See DOI:
10.1039/c4ra08233h
Fig. 1 Examples of biologically important 2(3H)-benzoxazolones.
39020 | RSC Adv., 2014, 4, 39020–39029
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
transformation.14 From green and sustainable chemistry
perspective, the more protocols the biorenewable sources can
be utilized and transformed, the less dependent on fossil-oil the
human society will be.15 And, the construction of a highly
branched “family tree” is also very imperative for a certain
platform compound.16 Bearing this in mind and in continuation
of our study for the development of new strategies and practical
technologies for biomass conversion,13,14 we herein describe a
one-pot and metal-free protocol for the efficient and rapid
synthesis of biologically important N-aryl-2(3H)-benzoxazolones
from 3-MDHS, anilines and bis(trichloromethyl) carbonate
(BTC).
Results and discussion
Scheme
1 Strategies for the construction of N-aryl-2(3H)-
Initially, 3-MDHS (1), aniline (2a) and bis(trichloromethyl)
carbonate (BTC, as the bifunctional reagent) were chosen as
model substrates to screen the optimal reaction conditions in
terms of solvent, catalyst and reaction temperature. Solvent
screening was carried out by using p-TsOH as the catalyst for
step 1 under microwave irradiation and Et3N as the base for step
2 at room temperature (Table 1, entries 1–9). It would be evident
from Table 1 that the identity of solvents was crucial for the
overall yield of this consecutive reaction. For example, only
moderate yields (68% and 75%, respectively) can be obtained
when the reaction was carried out in nonpolar solvents such as
CCl4 and CHCl3 (Table 1, entries 1 and 2), which can be
contributed to the low conversion to 3a in step 1 in these
solvents (monitored by TLC). Polar solvents such as DMSO,
DMF, NMP, ethanol, methanol, dioxane and CH3CN were also
screened. We have found that, although high conversion to
intermediate 3a was readily achieved in DMSO, DMF and NMP
(monitored by TLC), only trace amount of the desired product
4a was obtained in the nal reaction step (Table 1, entries 3–5).
To our delight, CH3CN proved to be an excellent medium for
both step 1 and step 2, affording 4a in 89% isolated yield (Table
1, entry 9). Moreover, no desired product was detected when the
consecutive reaction was carried out in protic solvents such as
ethanol and methanol, although they have been previously
shown to be excellent solvents for the preparation of interme-
diate 3a.14 This might be due to the competing side reaction
between hydroxyl group and BTC (Table 1, entries 6 and 7).
Subsequently, the effect of base and temperature on step 2 were
also studied by using CH3CN as the optimized solvent. The
result showed that the desired product 4a was obtained in an
excellent yield (92%) when BTC (1.5 equiv) was added into the
reaction mixture of step 1, and reacted in reux in absence of
Et3N under microwave irradiation (Table 1, entry 12). It is
noteworthy that, under this condition, the desired products 4a
could readily be obtained in pure form from the reaction
mixture by simply treating with aqueous Na2CO3, thus leading
to a more convenient procedure. Investigation on the different
amounts of BTC revealed that 1.5 equiv was the most optimal
for this reaction, whereas 0.5 equiv and 1.0 equiv of BTC
afforded lower yields (68% and 76%, respectively, entries 16 and
17), and no signicant improvement in the yield when
increasing the amount of BTC to 2.0 equiv (Table 1, entry 18). In
benzoxazolones.
Table 1 Screening of reaction conditionsa
Yieldc (%)
b
Entry
Solvent
Base
T1/T2 (ꢀC)
t1/t2 (min)
1
CCl4
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
—
—
—
Et3N
—
—
76/rt
60/rt
110/rt
110/rt
110/rt
78/rt
65/rt
100/rt
80/rt
50/90
60/90
6/120
6/120
6/120
30/120
35/120
20/120
15/90
15/90
15/25
15/5
68
75
2
3
CHCl3
DMF
Trace
Trace
Trace
NDd
NDd
78
4
5
DMSO
NMP
6
EtOH
7
8
9
MeOH
Dioxane
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
89
10
11
12
13
14
15
16
17
18
80/rt
Trace
72
80/50
80/80
80/80
80/80
80/80
80/80
80/80
80/80
92e
15/5
78
15/30
15/30
15/5
15/5
15/5
Tracef
Traceg
68h
—
—
—
76i
92j
a
Reaction conditions: 1 (0.19 g, 1.0 mmol), 2a (1.0 mmol), p-TsOH (0.05
mmol), solvent (5.0 ml), BTC (1.5 mmol, added in step 2) with or without
b
Et3N (6.0 mmol). The ramp time (0.5 min) is included as part of the
c
d
reaction time. Isolated yield. Not detected, only intermediate 3a
e
was obtained. Reaction conditions: 1 (0.19 g, 1.0 mmol), 2a (1.0
mmol), p-TsOH (0.05 mmol), CH3CN (5.0 ml) and BTC (1.5 mmol,
added in step 2) under microwave condition. Aer completion, the
reaction mixture was treated with aqueous Na2CO3 to afford the nal
f
product 4a. Urea was used as the bifunctional reagent for step 2.
g
Diethyl carbonate was used as the bifunctional reagent for step 2.
0.5 mmol BTC was used. 1.0 mmol BTC was used. 2.0 mmol BTC
h
i
j
was used.
subsequent consecutive reaction would then be conducted to
afford N-arylated 2-aminophenols, a class of functionalized
platform compounds with great potential for further
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 39020–39029 | 39021

View Article Online
RSC Advances
Paper
Table 2 Scope of the reactiona
Entry
1
Arylamine
t1/t2b (min)
Product
Yieldc (%)
15/5
92
2
3
4
5
13/3
12/3
15/5
20/6
95
93
87
87
6
7
20/6
85
79
20/10
8
9
20/8
83
80
20/10
39022 | RSC Adv., 2014, 4, 39020–39029
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 2 (Contd.)
Entry
10
Arylamine
t1/t2b (min)
Product
Yieldc (%)
15/10
89
11
12
13
20/10
20/10
20/10
76
90
69
14
15
16
25/10
25/10
—/—
67d
60d
NDe
17
18
20/8
84
76
25/10
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 39020–39029 | 39023

View Article Online
RSC Advances
Paper
Table 2 (Contd.)
Entry
19
Arylamine
t1/t2b (min)
Product
Yieldc (%)
25/10
75
20
15/5
93
82
21
20/10
a
Unless otherwise specied, all reactions were carried out using: 3-MDHS (0.19 g, 1.0 mmol), arylamine (1.0 mmol), p-TsOH (0.05 mmol), CH3CN
(5.0 ml), BTC (1.5 mmol) under microwave condition, aer completion, the reaction mixture was treated with aqueous Na2CO3 to afford the nal
product 4. b The ramp time (0.5 min) is included as part of the reaction time. c Isolated yield. d Puried by column chromatography (silica gel, 200–
300 mesh). e ND: not detected.
catalyst for step 1, and BTC (1.5 mmol) as the bifunctional
reagent for step 2 both under microwave conditions with reux
(Table 1, entry 12).
Having established the optimized conditions, we examined
the scope of the process using various substituted anilines
which bear different electronic and steric properties. In general,
moderate to excellent yields of N-aryl-2(3H)-benzoxazolones
were readily obtained (Table 2). It is apparent that the reactivity
of the anilines with an electron-donating group such as Me,
OMe (Table 2, entries 2 and 3) is higher than anilines possess-
ing an electron-withdrawing group such as COMe, NO2, CO2Me
(Table 2, entries 8, 9 and 18). For example, the consecutive
reaction of 4-methylaniline (2c), 3-MDHS and BTC in CH3CN
gave rise to the corresponding product 4c in 93% isolated yield
(Table 2, entry 3), whereas only a moderate yield (76%) of
product 4r was obtained when methyl 3-aminobenzoate (2r) was
Scheme 2 Consecutive reaction of 3-MDHS, BTC with 1-naphthyl-
amine, 4-chloroxenylamine and benzophenone hydrazone (t1 for step
used as the substrate (Table 2, entry 18). In addition, neither the
desired product nor the corresponding intermediate was
detected when 2,4-dinitroaniline (2p) was used as the substrate
(Table 2, entry 16), which may be due to the reduced nucleo-
philicity of the amino group. Halogen-substituted anilines were
also subjected to the optimized reaction conditions and were
found to be efficiently transformed into the corresponding N-
aryl-2(3H)-benzo-xazolones (Table 2, entries 4–7, 11, 13 and 17).
It could be concluded that the reactivity of 4-uoroaniline (2g)
1 and t2 for step 2).
addition, other bifunctional carbonylic reagents such as urea
and diethyl carbonate17 were also tested in step 2, but only
trace amount of the desired product was detected (Table 1,
entries 14 and 15). Therefore, we considered that the optimized
reaction conditions consist of: 3-MDHS (1.0 mmol), arylamine
(1.0 mmol) in CH3CN (5 ml) using p-TsOH (0.05 mmol) as the
39024 | RSC Adv., 2014, 4, 39020–39029
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
aspects of this methodology, thus representing an excellent
alternative to the former Diels–Alder- or Ullmann-reaction-
based methods. Besides, this consecutive reaction can also be
extended to the synthesis of a novel dibenz[b,e][1,4]oxazepin-11-
(5H)-one motif. Further investigations to develop this and our
previously reported protocols into practical applications for the
synthesis of various benzo-fused nitrogen-containing heterocy-
cles from 3-MDHS are underway in our laboratory.
Scheme 3 BTC catalyzed facile synthesis of 3-chloro-7-methoxy-
carbonyl dibenz[b,e][1,4]oxazepin-11(5H)-one.
Experimental section
General
was slightly lower as compared with the 4-bromoaniline (2e) or
4-iodoaniline (2d) (Table 2, entries 4, 5 and 7). It is worth noting
that all these halogen-substituted N-aryl-2(3H)-benzoxazolones
can be easily functionalized or transformed, thus making them
wonderful synthons for further transformation. Despite the
steric hindrance of the ortho-substituent arylamines, the cor-
responding N-aryl-2(3H)-benzoxazolones could smoothly be
obtained in moderate to good yields (Table 2, entries 10–15). For
instance, products 4j, 4k were isolated in satisfying yields (89%
and 76%, respectively) when 2-methylaniline (2j) and 2-chol-
roanilne (2k) were subjected to the optimized reaction condi-
tions. To our delight, it has been demonstrated that this
protocol was also applicable to polycyclic or pseudo arylamines.
As shown in Scheme 2, 1-naphthylamine (2v), benzophenone
hydrazone (2w) and 4-chloroxenylamine (2x) performed
smoothly in this consecutive reaction to afford the corre-
sponding N-aryl-2(3H)-benzoxazolones (4v, 4w and 4x, respec-
tively) in good to excellent yields. It is worth mentioning that the
compound 4x may be regarded as a close analogue of the
recently reported P2X3 receptor antagonist.4
(ꢁ)-Methyl 3-dehydroshikimate was readily prepared from
(ꢁ)-shikimic acid according to the ref. 14 (see the ESI† for
details). Unless special notice, all the other reagents were
obtained commercially and used without further purication.
Reactions were monitored by TLC and column chromatography
was performed on silica gel (200–300 mesh) using the EtOAc–PE
system as eluent (PE, 60–90 ꢀC). The reaction temperatures were
detected in real time using an infrared thermometer and the
ramp time (approximate 0.5 min) is included as part of the
reaction time. 1H NMR and 13C NMR spectra were recorded on a
400 MHz spectrometer (1H 400 MHz, 13C 100 MHz) using
CD3COCD3 or DMSO-d6 as the solvent. Chemical shis were
reported in parts per million (ppm) and are calibrated using
residual undeuterated solvent as an internal reference. HRMS
spectra analyses were carried out on a LC-Q-TOF (ESI) appa-
ratus. Mass spectrometry were measured on a Shimadzu GC-MS
QP5050A in electron ionization mode. Melting points were
measured on a Thiele apparatus and were uncorrected. All the
microwave reactions were carried out in a monomode scientic
microwave reactor with
pressure.
a condenser under atmosphere
Notably, when 2-amino-4-chlorobenzoic acid (2y), 3-MDHS
and BTC were subjected to this one-pot, two-step conditions, an
unexpected but interesting result was obtained with the isola-
tion of 3-chloro-7-methoxycarbonyl-dibenz[b,e][1,4]-oxazepin-
11(5H)-one (I) as the sole product, but not 5-methoxycarbonyl-3-
(5-chloro-2-carboxylphenyl)-2(3H)-benzox-azolone (4y). As shown
General procedure for the syntheses of N-aryl-2(3H)-
benzoxazolones (4a–4x)
To a solution of 3-MDHS (0.19 g, 1.0 mmol), arylamine (1.0
in Scheme 3, the reaction of 2-amino-4-chlorobenzoic acid (2y) mmol) in CH3CN (5 mL) was added p-TsOH (0.05 mmol). The
and 3-MDHS in step 1 gave a highly functionalized intermediate ask was then placed into the microwave reactor and the
3y, which bears an adjacent carboxyl group as well as a phenolic mixture was irradiated (240 W) with stirring for indicated
hydroxyl group, thus facilitating the lactonization under the minutes (t1). Then, BTC (1.5 mmol) was added and the result
catalysis of BTC to afford 3-chloro-7-methoxycarbonyl-dibenz[b,e]- mixture was irradiated (240 W) for the indicated minutes (t2).
[1,4]-oxazepin-11(5H)-one (I) in 82% isolated yield.
Aer completion (as monitored by TLC), the reaction mixture
was poured into sodium carbonate solution (50 mL, 5%) and
stirred vigorously, the resulting solid was ltered and dried to
furnish the desired product in pure form. The isolated products
Conclusion
In summary, a facile and efficient protocol for the one-pot could be further puried by recrystallization from EtOAc–PE or
construction of N-aryl-2(3H)-benzoxazolones from the biomass- by column chromatography using EtOAc–PE as eluent if
derived substrate 3-MDHS (1) via the N-arylated 2-aminophenol necessary.
intermediates under microwave condition has been estab-
5-Methoxycarbonyl-3-phenyl-2(3H)-benzoxazolone
(4a).
lished. A wide range of N-aryl-2(3H)-benzoxazolones have been White ake crystal; yield: 0.25 g (92%); mp 138–140 ꢀC; 1H NMR
smoothly synthesized in moderate to excellent yields via the (400 MHz, DMSO-d6): d ¼ 7.85 (dd, J ¼ 8.6, 1.6 Hz, 1H), 7.63 (d, J
sequential C–N bond-forming, aromatization and annulation ¼ 4.0 Hz, 4H), 7.57 (d, J ¼ 8.4 Hz, 1H), 7.53 (m, 1H), 7.44 (d, J ¼
reactions between 3-MDHS, anilines and BTC. The metal-free 1.6 Hz, 1H), 3.81 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼
reaction conditions, the short reaction times, the operational 165.4 (C]O), 152.3 (C]O), 145.6, 132.8, 131.7, 129.9, 128.8,
simplicity, as well as the broad substrate scope are the attractive 125.8, 125.5, 124.9, 110.2, 109.2, 52.3; IR (KBr) vmax/cmꢁ1 3050,
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 39020–39029 | 39025

View Article Online
RSC Advances
Paper
2988, 2950, 1777, 1709, 1620, 1596, 1505, 1467, 1380, 1284, 1409, 1385, 1284, 1242, 1107, 1006, 837; MS(EI): m/z (%) ¼ 305
1246, 761, 691; MS (EI): m/z (%) ¼ 269 ([M]+, 100), 238 ([M ꢁ ([M + 2]+, 33), 303 ([M]+, 100), 272 ([M ꢁ OCH3]+, 62), 244 ([M ꢁ
OCH3]+, 94), 210 ([M ꢁ COOCH3]+, 15), 194 (18), 166 (16); HRMS COOCH3]+, 11); HRMS (ESI-TOF): m/z [M + H]+ calcd for
(ESI-TOF): m/z [M + H]+ calcd for C15H12NO4: 270.0761; found:
C
15H11Cl35NO4: 304.0371; found: 304.0364.
270.0763.
3-(4-Fluorophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone
5-Methoxycarbonyl-3-(4-methoxyphenyl)-2(3H)-benzoxazolone (4g). White solid; yield: 0.23 g (79%); mp > 200 ꢀC; 1H NMR (400
(4b). White crystal; yield: 0.28 g (95%); mp 124–126 ꢀC; 1H NMR MHz, DMSO-d6): d ¼ 7.86 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.69–7.73 (m,
(400 MHz, DMSO-d6): d ¼ 7.84 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.54– 2H), 7.58 (d, J ¼ 8.4 Hz, 1H), 7.46–7.50 (m, 2H), 7.41 (d, J ¼ 1.6
7.57 (m, 3H), 7.36 (d, J ¼ 1.6 Hz, 1H), 7.16 (dd, J ¼ 6.8, 2.0 Hz, Hz, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼ 165.4
2H), 3.84 (s, 3H), 3.81 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼ (C]O), 162.8 (d, 1JCF ¼ 244.7 Hz), 152.4, 145.5, 131.8, 129.0 (d,
165.5 (C]O), 159.4 (C]O), 152.6, 145.5, 132.3, 127.6, 125.5, 4JCF ¼ 2.6 Hz), 128.5 (d, 3JCF ¼ 9.0 Hz), 125.5, 124.9, 116.9 (d, 2JCF
125.1, 124.7, 115.1, 110.1, 109.1, 55.5, 52.3; MS (EI): m/z (%) ¼ ¼ 23.0 Hz), 110.1, 109.1, 52.3; IR (KBr) vmax/cmꢁ1 3064, 2997,
299 ([M]+, 100), 284 ([M ꢁ CH3]+, 7), 268 ([M ꢁ OCH3]+, 18), 240 2953, 2845, 1782, 1707, 1624, 1514, 1459, 1420, 1384, 1285,
([M ꢁ COOCH3]+, 14), 196 (7); HRMS (ESI-TOF): m/z [M + H]+ 1249, 1103, 1008, 844, 765; MS (EI): m/z (%) ¼ 287 ([M]+, 100),
calcd for C16H14NO5: 300.0866; found: 300.0874.
256 ([M ꢁ OCH3]+, 73), 228 ([M ꢁ COOCH3]+, 11), 212 (17);
5-Methoxycarbonyl-3-(4-methylphenyl)-2(3H)-benzoxazolone HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H11FNO4: 288.0667;
(4c). White acicular crystal; yield: 0.26 g (93%); mp 147–149 ꢀC; found: 288.0660.
1H NMR (400 MHz, DMSO-d6): d ¼ 7.85 (dd, J ¼ 8.4, 1.6 Hz, 1H),
3-(4-Acetylphenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone
7.56 (d, J ¼ 8.4 Hz, 1H), 7.51 (d, J ¼ 8.0 Hz, 2H), 7.43 (d, J ¼ 8.4 (4h). Gray solid; yield: 0.26 g (83%); mp > 200 ꢀC; 1H NMR (400
Hz, 2H), 7.40 (d, J ¼ 1.6 Hz, 1H), 3.81 (s, 3H), 2.40 (s, 3H); 13C MHz, DMSO-d6): d ¼ 8.19 (d, J ¼ 8.4 Hz, 2H), 7.88 (dd, J ¼ 8.4,
NMR (100 MHz, DMSO-d6): d ¼ 165.4 (C]O), 152.4 (C]O), 1.2 Hz, 1H), 7.81 (d, J ¼ 8.4 Hz, 2H), 7.60 (d, J ¼ 8.4 Hz, 1H), 7.56
145.5, 138.6, 131.9, 130.3, 130.1, 125.7, 125.5, 124.8, 110.1, (d, J ¼ 1.2 Hz, 1H), 3.82 (s, 3H), 2.65 (s, 3H); 13C NMR (100 MHz,
109.2, 52.3, 20.7; IR (KBr) vmax/cmꢁ1 3120, 3095, 3002, 2954, DMSO-d6): d ¼ 197.1 (C]O), 165.4 (C]O), 152.0 (C]O), 145.6,
2924, 1780, 1733, 1609, 1521, 1490, 1452, 1388, 1289, 1248, 835; 136.8, 136.4, 131.1, 129.8, 125.6, 125.4, 125.2, 110.3, 109.5, 52.4,
MS (EI): m/z (%) ¼ 283 ([M]+, 100), 252 ([M ꢁ OCH3]+, 48), 224 26.8; IR (KBr) vmax/cmꢁ1 3012, 2961, 2857, 1778, 1711, 1678,
([M ꢁ COOCH3]+, 6), 180 (18), 152 (4); HRMS (ESI-TOF): m/z [M + 1600, 1514, 1490, 1451, 1380, 1294, 1264, 1091, 1006, 844, 766;
H]+ calcd for C16H14NO4: 284.0917; found: 284.0921.
MS (EI): m/z (%) ¼ 311 ([M]+, 54), 296 ([M ꢁ CH3]+, 100), 280
3-(4-Iodophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone ([M ꢁ OCH3]+, 12); HRMS (ESI-TOF): m/z [M + H]+ calcd for
1
ꢀ
(4d). Grey solid; yield: 0.34 g (87%); mp 169–171 C; H NMR
(400 MHz, DMSO-d6): d ¼ 8.00 (d, J ¼ 8.4 Hz, 2H), 7.86 (dd, J ¼
C
17H14NO5: 312.0866; found: 312.0864.
5-Methoxycarbonyl-3-(4-nitrophenyl)-2(3H)-benzoxazolone
8.4, 1.6 Hz, 1H), 7.57 (d, J ¼ 8.4 Hz, 1H), 7.48 (d, J ¼ 1.6 Hz, 1H), (4i). Yellow solid; yield: 0.25 g (80%); mp > 200 ꢀC; 1H NMR (400
7.46 (d, J ¼ 8.4 Hz, 2H), 3.82 (s, 3H); 13C NMR (100 MHz, DMSO- MHz, DMSO-d6): d ¼ 8.48 (dd, J ¼ 6.8, 2.0 Hz, 2H), 7.96 (dd, J ¼
d6): d ¼ 165.4 (C]O), 152.1 (C]O), 145.6, 138.7, 132.6, 131.3, 6.8, 2.0 Hz, 2H), 7.90 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.64 (d, J ¼ 1.6 Hz,
127.8, 125.5, 125.0, 110.2, 109.3, 94.7, 52.3; IR (KBr) vmax/cmꢁ1 1H), 7.62 (d, J ¼ 8.4 Hz, 1H), 3.83 (s, 3H); 13C NMR (100 MHz,
3112, 3083, 3059, 2964, 1776, 1713, 1618, 1497, 1458, 1422, DMSO-d6): d ¼ 165.4 (C]O), 151.8 (C]O), 146.5, 145.7, 138.6,
1382, 1290, 1250, 1199, 1004, 824; MS (EI): m/z (%) ¼ 395 ([M]+, 130.7, 126.2, 125.7, 125.5, 125.2, 110.4, 109.7, 52.4; IR (KBr)
100), 364 ([M ꢁ OCH3]+, 38), 182 (16), 153 (13); HRMS (ESI-TOF): vmax/cmꢁ1 3122, 3084, 3062, 3003, 2950, 2840, 1788, 1727, 1596,
m/z [M + H]+ calcd for C15H11INO4: 395.9727; found: 395.9730. 1523, 1503, 1455, 1380, 1314, 1288, 1263, 1148, 1006, 830, 761;
3-(4-Bromophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone MS (EI): m/z (%) ¼ 314 ([M]+, 100), 283 ([M ꢁ OCH3]+, 94), 255
(4e). White solid; yield: 0.30 g (87%); mp 168–170 C; H NMR ([M ꢁ COOCH3]+, 6); HRMS (ESI-TOF): m/z [M + Na]+ calcd for
1
ꢀ
(400 MHz, DMSO-d6): d ¼ 7.83–7.88 (m, 3H), 7.62 (dd, J ¼ 6.8,
2.0 Hz, 2H), 7.58 (d, J ¼ 8.4 Hz, 1H), 7.48 (d, J ¼ 1.6 Hz, 1H), 3.82
C
15H10N2NaO6: 337.0431; found: 337.0432.
5-Methoxycarbonyl-3-(2-methylphenyl)-2(3H)-benzoxazolone
(s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼ 165.4 (C]O), 152.1 (4j). White solid; yield: 0.25 g (89%); mp 138–140 C; H NMR
(C]O), 145.5, 132.9, 132.1, 131.4, 127.9, 125.6, 125.0, 121.6, (400 MHz, DMSO-d6): d ¼ 7.86 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.60 (d, J
110.2, 109.3, 52.3; IR (KBr) vmax/cmꢁ1 3102, 3069, 2992, 2838, ¼ 8.4 Hz, 1H), 7.50–7.55 (m, 3H), 7.42–7.46 (m, 1H), 7.13 (d, J ¼
1776, 1727, 1619, 1498, 1459, 1401, 1382, 1281, 1237, 1149, 1.6 Hz, 1H), 3.79 (s, 3H), 2.15 (s, 3H); 13C NMR (100 MHz,
1005, 829; MS (EI): m/z (%) ¼ 349 ([M + 2]+, 94), 347 ([M]+, 100), DMSO-d6): d ¼ 165.4 (C]O), 152.1 (C]O), 145.8, 136.0, 132.1,
318 (53), 316 ([M ꢁ OCH3]+, 55); HRMS (ESI-TOF): m/z [M + H]+ 131.6, 131.0, 130.1, 128.1, 127.6, 125.7, 124.9, 110.3, 109.1, 52.3,
1
ꢀ
calcd for C15H11Br79NO4: 347.9866; found: 347.9862.
17.0; IR (KBr) vmax/cmꢁ1 3116, 3084, 3056, 3001, 2955, 1777,
3-(4-Chlorophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone 1720, 1620, 1499, 1450, 1378, 1354, 1288, 1247, 1145, 1089, 998,
(4f). White acicular crystal; yield: 0.26 g (85%); mp 144–146 ꢀC; 761; MS (EI): m/z (%) ¼ 283 ([M]+, 100), 252 ([M ꢁ OCH3]+, 32),
1H NMR (400 MHz, DMSO-d6): d ¼ 7.86 (dd, J ¼ 8.4, 1.6 Hz, 1H), 224 ([M ꢁ COOCH3]+, 5); HRMS (ESI-TOF): m/z [M + H]+ calcd for
7.66–7.72 (m, 4H), 7.57 (d, J ¼ 8.4 Hz, 1H), 7.47 (d, J ¼ 1.6 Hz,
C
16H14NO4: 284.0917; found: 284.0920.
3-(2-Chlorophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone
1H), 3.82 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼ 165.4
1
ꢀ
(C]O), 152.1 (C]O), 145.5, 133.2, 131.7, 131.4, 129.9, 127.6, (4k). White solid; yield: 0.23 g (76%); mp 152–154 C; H NMR
125.5, 125.0, 110.2, 109.3, 52.3; IR (KBr) vmax/cmꢁ1 3096, 3057, (400 MHz, DMSO-d6): d ¼ 7.88 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.80–
2994, 2946, 2888, 2839, 1781, 1710, 1623, 1502, 1460, 1434, 7.85 (m, 2H), 7.60–7.69 (m, 3H), 7.19 (d, J ¼ 1.2 Hz, 1H), 3.79
39026 | RSC Adv., 2014, 4, 39020–39029
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
(s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼ 165.3 (C]O), 151.8
(C]O), 145.6, 132.0, 131.6, 131.5, 130.8, 130.6, 129.6, 129.1,
125.8, 125.2, 110.5, 109.3, 52.3; IR (KBr) vmax/cmꢁ1 3070, 2954,
1782, 1715, 1620, 1587, 1499, 1458, 1382, 1283, 1248, 1091,
1001, 956, 761; MS (EI): m/z (%) ¼ 305 ([M + 2]+, 33), 303 ([M]+,
100), 272 ([M ꢁ OCH3]+, 80), 244 ([M ꢁ COOCH3]+, 12); HRMS:
(ESI-TOF) m/z [M + H]+ calcd. for C15H11Cl35NO4: 304.0371;
found: 304.0364.
3-(3-Chlorophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone
1
ꢀ
(4q). White solid; yield: 0.25 g (84%); mp 145–147 C; H NMR
(400 MHz, DMSO-d6): d ¼ 7.86 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.79 (d, J
¼ 1.6 Hz, 1H), 7.58–7.70 (m, 4H), 7.47 (d, J ¼ 1.6 Hz, 1H), 3.82 (s,
3H); 13C NMR (100 MHz, DMSO-d6): d ¼ 165.4 (C]O), 152.2
(C]O), 145.5, 134.1, 133.9, 131.5, 131.4, 128.9, 126.0, 125.6,
125.1, 124.6, 110.3, 109.3, 52.4; IR (KBr) vmax/cmꢁ1 3125, 3093,
3063, 2959, 1798, 1725, 1623, 1594, 1496, 1459, 1437, 1383,
1293, 1265, 1149, 1094, 1008, 868, 783, 709; MS (EI): m/z (%) ¼
305 ([M + 2]+, 33), 303 ([M]+, 100), 272 ([M ꢁ OCH3]+, 84), 244 ([M
ꢁ COOCH3]+, 11); HRMS (ESI-TOF): m/z [M + H]+ calcd. for
5-Methoxycarbonyl-3-(2-methoxyphenyl)-2(3H)-benzoxazolone
(4l). White acicular crystal; yield: 0.27 g (90%); mp 164–166 ꢀC;
1H NMR (400 MHz, DMSO-d6) d: ppm 7.84 (dd, J ¼ 8.4, 1.6 Hz,
1H), 7.56–7.60 (m, 3H), 7.33 (d, J ¼ 8.4 Hz, 1H), 7.14–7.19 (m,
2H), 3.79 (s, 3H), 3.78 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼
165.7 (C]O), 155.1 (C]O), 152.6, 145.8, 132.3, 131.8, 129.5,
125.9, 125.1, 121.4, 120.4, 113.3, 110.4, 109.7, 56.2, 52.6; IR
(KBr) vmax/cmꢁ1 3139, 3081, 3023, 2979, 2956, 2834, 1781, 1731,
1618, 1599, 1510, 1490, 1380, 1289, 1250, 1095, 1019, 759, 743;
MS (EI): m/z (%) ¼ 299 ([M]+, 100), 268 ([M ꢁ OCH3]+, 22), 240
([M ꢁ COOCH3]+, 8); HRMS (ESI-TOF): m/z [M + H]+ calcd for
C
15H11Cl35NO4: 304.0371; found: 304.0367.
5-Methoxycarbonyl-3-(3-(methoxycarbonyl)phenyl)-2(3H)-
benzoxazolone (4r). White solid; yield: 0.25 g (76%); mp >
200 ꢀC; 1H NMR (400 MHz, DMSO-d6): d ¼ 8.21 (s, 1H), 8.09 (d,
J ¼ 7.6 Hz, 1H), 7.95 (d, J ¼ 0.8 Hz, 1H), 7.87 (dd, J ¼ 8.4, 1.6 Hz,
1H), 7.79 (t, J ¼ 8.0 Hz, 1H), 7.58 (d, J ¼ 8.4 Hz, 1H), 7.46 (d, J ¼
1.2 Hz, 1H), 3.89 (s, 3H), 3.81 (s, 3H); 13C NMR (100 MHz,
DMSO-d6): d ¼ 165.4 (C]O), 165.3 (C]O), 152.3 (C]O), 145.6,
133.3, 131.6, 131.3, 130.5, 130.5, 129.3, 126.6, 125.5, 125.0,
110.2, 109.1, 52.5, 52.3; IR (KBr) vmax/cmꢁ1 3095, 3077, 3060,
3005, 2958, 2845, 1779, 1713, 1623, 1587, 1492, 1349, 1281,
1243, 1110, 1016, 890, 755, 697; MS (EI): m/z (%) ¼ 327 ([M]+,
100), 296 ([M ꢁ OCH3]+, 82), 268 ([M ꢁ COOCH3]+, 4); HRMS
(ESI-TOF): m/z [M + Na]+ calcd for C17H13NaO6: 350.0635; found:
350.0640.
C
16H14NO5: 300.0866; found: 300.0872.
5-Methoxycarbonyl-3-(2,5-dichlorophenyl)-2(3H)-benzoxazolone
(4m). White solid; yield: 0.23 g (69%); mp 182–184 ꢀC; 1H NMR
(400 MHz, DMSO-d6): d ¼ 8.04 (d, J ¼ 2.4 Hz, 1H), 7.88 (dd, J ¼
8.4, 1.6 Hz, 1H), 7.85 (d, J ¼ 8.8 Hz, 1H), 7.76 (dd, J ¼ 8.4, 2.8 Hz,
1H), 7.63 (d, J ¼ 8.4 Hz, 1H), 7.31 (d, J ¼ 1.6 Hz, 1H), 3.80 (s, 3H);
13C NMR (100 MHz, DMSO-d6): d ¼ 165.3 (C]O), 151.7 (C]O),
145.5, 132.8, 132.1, 132.0, 131.2, 130.9, 130.7, 130.6, 125.9,
125.4, 110.5, 109.7, 52.4; IR (KBr) vmax/cmꢁ1 3121, 3095, 3036,
2997, 2953, 2846, 1770, 1722, 1617, 1568, 1492, 1453, 1409,
1362, 1287, 1253, 1196, 1150, 1100, 1006, 765, 717; MS (EI): m/z
(%) ¼ 341 ([M + 4]+, 12), 339 ([M + 2]+, 69), 337 ([M]+, 100), 306
([M ꢁ OCH3]+, 82), 278 ([M ꢁ COOCH3]+, 4); HRMS (ESI-TOF):
m/z [M + H]+ calcd for C15H10Cl235NO4: 337.9981; found:
337.9976.
3-(3-(Triuoromethyl)phenyl)-5-methoxycarbonyl-2(3H)-ben-
zoxazolone (4s). White solid; yield: 0.25 g (75%); mp 128–130 ꢀC;
1H NMR (400 MHz, DMSO-d6): d ¼ 8.08 (s, 1H), 7.99 (d, J ¼ 7.6
Hz, 1H), 7.86–7.93 (m, 3H), 7.60 (d, J ¼ 8.4 Hz, 1H), 7.48 (d, J ¼
1.6 Hz, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼
165.4 (C]O), 152.2 (C]O), 145.5, 133.7, 131.4, 131.2, 130.6 (q,
3
2JCF ¼ 32.1 Hz), 130.0, 125.6, 125.5 (q, JCF ¼ 3.4 Hz), 125.1,
123.0 (q, 3JCF ¼ 3.4 Hz), 122.2 (q, 1JCF ¼ 271.2 Hz), 110.2, 109.2,
52.3; IR (KBr) vmax/cmꢁ1 3086, 3056, 3018, 2964, 1787, 1720,
1625, 1503, 1460, 1435, 1387, 1329, 1294, 1260, 1182, 1116, 882,
765, 700; MS (EI): m/z (%) ¼ 337 ([M]+, 90), 306 ([M ꢁ OCH3]+,
100), 278 ([M ꢁ COOCH3]+, 15); HRMS (ESI-TOF): m/z [M + Na]+
calcd for C16H10F3NNaO4: 360.0454; found: 360.0460.
5-Methoxycarbonyl-3-(2,4,6-trimethylphenyl)-2(3H)-benzoxa-
zolone (4n). White solid; yield: 0.21 g (67%); mp 164–166 ꢀC; 1H
NMR (400 MHz, DMSO-d6): d ¼ 7.47 (d, J ¼ 8.2 Hz, 1H) 7.25 (dd,
J ¼ 8.2, 2.0 Hz, 1H), 6.98 (s, 2H), 6.60 (d, J ¼ 2.0 Hz, 1H), 3.71 (s,
3H), 2.26 (s, 3H), 2.04 (s, 6H); 13C NMR (100 MHz, DMSO-d6): d
¼ 165.9 (C]O), 151.2 (C]O), 140.5, 139.5, 136.5, 135.7, 133.8,
5-Methoxycarbonyl-3-(3-methylphenyl)-2(3H)-benzoxazolone
1
ꢀ
129.6, 129.1, 122.9, 117.2, 112.1, 52.1, 20.6, 17.6; IR (KBr) vmax
/
(4t). White solid; 0.26 g (93%); mp 114–116 C; H NMR (400
MHz, DMSO-d6): d ¼ 7.84 (dd, J ¼ 8.4, 1.6 Hz, 1H), 7.56 (d, J ¼
8.4 Hz, 1H), 7.51 (t, J ¼ 8.0 Hz, 1H), 7.40–7.44 (m, 3H), 7.35 (d, J
¼ 7.6 Hz, 1H), 3.81 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz,
DMSO-d6): d ¼ 165.4 (C]O), 152.3 (C]O), 145.5, 139.6, 132.6,
131.7, 129.7, 129.5, 126.2, 125.5, 124.9, 122.8, 110.1, 109.2, 52.3,
20.8; IR (KBr) vmax/cmꢁ1 3073, 3002, 2955, 2924, 2848, 1776,
1712, 1623, 1606, 1590, 1499, 1457, 1384, 1283, 1247, 1087, 999,
887, 763, 702; MS (EI): m/z (%) ¼ 283 ([M]+, 100), 252 ([M ꢁ
OCH3]+, 54), 224 ([M ꢁ COOCH3]+, 7); HRMS (ESI-TOF): m/z [M +
H]+ calcd for C16H14NO4: 284.0917; found: 284.0920.
cmꢁ1 3012, 2951, 2918, 2856, 1781, 1728, 1697, 1612, 1520,
1483, 1444, 1377, 1299, 1207, 1160, 1001, 762; MS (EI): m/z (%) ¼
311 ([M]+, 33), 285 (100); HRMS (ESI-TOF): m/z [M + Na]+ calcd
for C18H17NNaO4: 334.1050; found: 334.1048.
3-(2,6-Diethylphenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone
1
ꢀ
(4o). White solid; yield: 0.19 g (60%); mp 173–175 C; H NMR
(400 MHz, DMSO-d6): d ¼ 7.49 (d, J ¼ 8.4 Hz, 2H) 7.21–7.28 (m,
3H), 6.63 (d, J ¼ 1.6 Hz, 1H), 3.71 (s, 3H), 2.46–2.52 (m, 4H), 1.01 (t,
J ¼ 7.6 Hz, 6H); 13C NMR (100 MHz, DMSO-d6): d ¼ 165.8 (C]O),
151.2 (C]O), 142.7, 140.3, 140.1, 135.3, 128.5, 127.4, 126.7, 122.9,
117.1, 112.4, 52.1, 23.9, 14.5; IR (KBr) vmax/cmꢁ1 3067, 3030, 2963,
2875, 1781, 1731, 1693, 1611, 1520, 1444, 1373, 1209, 1160, 1115,
1000, 798, 762, 716; MS (EI): m/z (%) ¼ 325 ([M]+, 20), 299 (100),
294 ([M ꢁ OCH3]+, 8), 266 ([M ꢁ COOCH3]+, 10); HRMS (ESI-TOF):
m/z [M + Na]+ calcd for C19H19NNaO4: 348.1206; found: 348.1207.
3-(3-Nitrophenyl)-5-methoxycarbonyl-2(3H)-benzoxazolone
(4u). Yellow solid; 0.26 g (82%); mp > 200 ꢀC; 1H NMR (400 MHz,
DMSO-d6): d ¼ 8.53 (t, J ¼ 2.0 Hz, 1H), 8.35–8.39 (m, 1H), 8.12–
8.15 (m, 1H), 7.93 (t, J ¼ 8.0 Hz, 1H), 7.88 (dd, J ¼ 8.4, 1.6 Hz,
1H), 7.60 (d, J ¼ 8.4 Hz, 1H), 7.57 (d, J ¼ 1.6 Hz, 1H), 3.82 (s, 3H);
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 39020–39029 | 39027

View Article Online
RSC Advances
Paper
13C NMR (100 MHz, DMSO-d6): d ¼ 165.7 (C]O), 152.4 (C]O),
148.7, 145.8, 134.1, 132.5, 131.6, 131.4, 125.8, 125.5, 123.7,
121.2, 110.5, 109.6, 52.6; IR (KBr) vmax/cmꢁ1 3132, 3102, 2999,
2952, 1780, 1710, 1621, 1536, 1494, 1439, 1373, 1297, 1258,
1151, 1094, 885, 767, 701; MS (EI): m/z (%) ¼ 314 ([M]+, 100), 283
([M ꢁ OCH3]+, 90), 255 ([M ꢁ COOCH3]+, 6); HRMS (ESI-TOF):
m/z [M + Na]+ calcd for C15H10N2NaO6: 337.0431; found:
337.0431.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21272280, 81201716, 81301890), Science
& Technology Program of Guangdong Province and Guangzhou
City (2011A081401002, 2014J4100224), Guang-dong Natural
Science Foundation (S2013010014278), National Signicant
New Drugs Development (2011ZX09202-101-07). The authors
are also grateful to Guangxi Wanshan Spice Co. Ltd. for giving
high quality (ꢁ)-shikimic acid as a gi.
5-Methoxycarbonyl-3-(naphthalen-1-yl)-2(3H)-benzoxazolone
1
ꢀ
(4v). Yellow solid; 0.26 g (80%); mp 120–122 C; H NMR (400
MHz, DMSO-d6): d ¼ 8.23 (d, J ¼ 8.4 Hz, 1H), 8.16 (d, J ¼ 8.4 Hz,
1H), 7.87–7.91 (m, 2H), 7.73–7.80 (m, 2H), 7.65–7.69 (m, 2H),
7.57–7.61 (m, 1H), 7.02 (d, J ¼ 1.2 Hz, 1H), 3.74 (s, 3H); 13C NMR
(100 MHz, DMSO-d6): d ¼ 165.3 (C]O), 152.8 (C]O), 146.0,
134.1, 132.9, 130.4, 129.0, 128.7, 128.5, 127.7, 127.1, 126.8,
126.1, 125.6, 124.9, 122.2, 110.3, 109.1, 52.2; IR (KBr) vmax/cmꢁ1
3058, 3000, 2953, 2846, 1790, 1723, 1621, 1599, 1511, 1492,
1455, 1373, 1291, 1247, 1148, 1047, 800, 773; HRMS (ESI-TOF):
m/z [M + H]+ calcd for C19H14NO4: 320.0917; found: 320.0922.
3-((Diphenylmethylene)amino)-5-methoxycarbonyl-2(3H)-
benzoxazolone (4w). White solid; 0.29 g (78%); mp 119–121 ꢀC;
1H NMR (400 MHz, DMSO-d6): d ¼ 7.82 (dd, J ¼ 8.4, 1.6 Hz, 1H),
7.66–7.74 (m, 4H), 7.53–7.57 (m, 2H), 7.40–7.57 (m, 4H), 7.29–
7.31 (m, 2H), 3.85 (s, 3H); 13C NMR (100 MHz, DMSO-d6): d ¼
178.6 (C]O), 165.4 (C]O), 147.7, 144.1, 135.3, 133.6, 132.6,
130.5, 130.2, 129.5, 128.7, 128.5, 127.7, 125.9, 124.9, 110.2,
109.7, 52.3; IR (KBr) vmax/cmꢁ1 3056, 3032, 3007, 2957, 2848,
1787, 1717, 1620, 1560, 1490, 1460, 1366, 1288, 1244, 1093,
1003, 763, 695; MS (EI): m/z (%) ¼ 372 ([M]+, 28), 341 ([M ꢁ
OCH3]+, 4), 180 (100); HRMS (ESI-TOF): m/z [M + H]+ calcd for
Notes and references
1 A. Porzelle, M. D. Woodrow and N. C. O. Tomkinson, Org.
Lett., 2010, 12, 812.
2 A. Guardigl, W. Chow, P. m. Martwins and M. S. Lefar, J.
Agric. Food Chem., 1971, 19, 742.
3 G. Q. Shi, J. F. Dropinski, B. M. McKeever, S. H. Xu,
J. W. Becker, J. P. Berger, K. L. MacNaul, A. Elbrecht,
G. C. Zhou, T. W. Doebber, P. R. Wang, Y. S. Chao,
M. Forrest, J. V. Heck, D. E. Moller and A. B. Jones, J. Med.
Chem., 2005, 48, 4457.
4 L. Chen, M. P. Dillon, L. C. Feng and M. M. Yang, US Patent
0324069, 2010.
5 (a) D. V. Dekhane, S. S. Pawar, S. V. Gupta, M. S. Shingare and
S. N. Thore, Lett. Org. Chem., 2011, 8, 406; (b) B. Gabriele,
R. Mancuso, G. Salerno and M. Costa, J. Org. Chem., 2003,
68, 601; (c) A. Noujima, T. Mitsudome, T. Mizugaki,
K. Jitsukawa and K. Kaneda, Green Chem., 2013, 15, 608; (d)
L. Troisi, C. Granito, S. Perrone and F. Rosato, Tetrahedron
Lett., 2011, 52, 4330; (e) X. F. Wang, G. Ling, Y. Xue and
S. W. Lu, Eur. J. Org. Chem., 2005, 1675.
C
22H17N2O4: 373.1183; found: 373.1185.
3-(40-Chloro-[1,10-biphenyl]-4-yl)-5-methoxycarbonyl-2(3H)-
benzoxazolone (4x). White solid; 0.34 g (90%); mp 187–189 ꢀC;
1H NMR (400 MHz, DMSO-d6): d ¼ 7.94 (d, J ¼ 8.4 Hz, 2H), 7.88
(dd, J ¼ 8.4, 1.2 Hz, 1H), 7.81 (d, J ¼ 8.4 Hz, 2H), 7.75 (d, J ¼ 8.4
Hz, 2H), 7.61 (d, J ¼ 8.4 Hz, 1H), 7.58 (d, J ¼ 8.4 Hz, 2H), 7.53 (d,
J ¼ 1.2 Hz, 1H), 3.84 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d:
ppm 165.5 (C]O), 152.4 (C]O), 145.6, 139.1, 137.8, 132.9,
132.4, 131.6, 129.0, 128.7, 128.1, 126.3, 125.6, 125.0, 110.3,
109.3, 52.4; IR (KBr) vmax/cmꢁ1 3042, 2960, 1786, 1719, 1620,
1522, 1490, 1459, 1383, 1286, 1241, 1092, 1007, 810, 762; HRMS:
(ESI-TOF) m/z [M + H]+ calcd. for C21H15ClNO4: 380.0684; found:
380.0681.
6 (a) R. Bautista, A. Benavides, H. A. Jimenez-Vazquez and
J. Tamariz, Nat. Prod. Res., 2013, 27, 1749; (b) P. Bernal and
J. Tarnariz, Helv. Chim. Acta, 2007, 90, 1449.
7 (a) M. T. Barros, S. S. Dey, C. D. Maycock and P. Rodrigues,
Chem. Commun., 2012, 48, 10901; (b) J. Cossy and
D. Belotti, Org. Lett., 2002, 4, 2557; (c) S. A. Girard, X. Hu,
T. Knauber, F. Zhou, M. O. Simon, G. J. Deng and C. J. Li,
Org. Lett., 2012, 14, 5606; (d) A. Hajra, Y. Wei and
N. Yoshikai, Org. Lett., 2012, 14, 5488; (e) T. Ishikawa,
E. Uedo, R. Tani and S. Saito, J. Org. Chem., 2001, 66, 186;
(f) Y. J. Xie, S. W. Liu, Y. Liu, Y. Q. Wen and G. J. Deng,
Org. Lett., 2012, 14, 1692.
8 J. W. Zhao, H. W. Huang, W. Q. Wu, H. J. Chen and
H. F. Jiang, Org. Lett., 2013, 15, 2604.
9 J. E. Richman, Y. C. Chang, S. Kambourakis, K. M. Draths,
E. Almy, K. D. Snell, G. M. Strasburg and J. W. Frost, J. Am.
Chem. Soc., 1996, 118, 11587.
3-Chloro-7-methoxycarbonyl-dibenz[b,e][1,4]oxazepin-11(5H)-
1
ꢀ
one (I). Yellow solid; 0.25 g (82%); mp > 200 C; HNMR (400
MHz, DMSO-d6): d ¼ 9.33 (s, 1H), 7.87 (d, J ¼ 8.8 Hz, 1H), 7.83 (d,
J ¼ 2.4 Hz, 1H), 7.64 (dd, J ¼ 8.8, 2.4 Hz, 1H), 7.30 (d, J ¼ 8.4 Hz,
1H), 7.24 (d, J ¼ 2.0 Hz, 1H), 6.99 (dd, J ¼ 8.4, 2.0 Hz, 1H), 3.84 (s,
3H); 13C NMR (100 MHz, DMSO-d6) d: ppm 165.1 (C]O), 163.3
(C]O), 149.6, 145.1, 139.8, 136.7, 136.3, 127.5, 125.1, 122.5,
121.2, 120.5, 118.4, 114.2, 52.3; IR (KBr) vmax/cmꢁ1 3313, 3079, 10 N. Q. Ran, D. R. Knop, K. M. Draths and J. W. Frost, J. Am.
3038, 3010, 2963, 2921, 1725, 1698, 1617, 1600, 1536, 1509, 1477,
Chem. Soc., 2001, 123, 10927.
1436, 1409, 1281, 1211, 1025, 1021, 766; MS (EI): m/z (%) ¼ 303 11 W. S. Li, D. M. Xie and J. W. Frost, J. Am. Chem. Soc., 2005,
([M]+, 16), 272 ([M ꢁ OCH3]+, 36), 244 ([M ꢁ COOCH3]+, 22);
127, 2874.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H11ClNO4: 304.0371; 12 S. Kambourakis and J. W. Frost, J. Org. Chem., 2000, 65, 6904.
found: 304.0366.
13 Y. Zou, E. S. Zhang, T. L. Xu, W. Wu, Y. Chen, M. Yuan,
W. Wei and X. Zhang, RSC Adv., 2013, 3, 6545.
39028 | RSC Adv., 2014, 4, 39020–39029
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
14 (a) W. Wu, Y. Zou, Y. Chen, J. Li, Z. L. Lv, W. Wei, T. K. Huang
and X. K. Liu, Green Chem., 2012, 14, 363; (b) E. S. Zhang,
T. L. Xu, D. J. Wang, T. K. Huang, M. Yuan, J. Li and
Y. Zou, RSC Adv., 2014, 4, 10022; (c) E. S. Zhang, T. L. Xu,
W. Wei, T. K. Huang, M. Yuan, W. Zeng and Y. Zou,
Synthesis, 2014, 46, 1167.
L. J. Zhang, Y. X. Da, Z. J. Quan, L. J. Yang and X. C. Wang,
RSC Adv., 2013, 3, 9201; (g) B. Wang, Y. Shen, J. K. Sun,
F. Xu and R. C. Sun, RSC Adv., 2014, 4, 18917; (h)
T. J. Schwartz, B. H. Shanks and J. A. Dumesic, Green
Chem., 2012, 14, 1850; (i) B. Saha and M. M. Abu-Omar,
Green Chem., 2014, 16, 24.
15 (a) E. Arceo, J. A. Ellman and R. G. Bergman, ChemSusChem., 16 B. Kamm, Angew Chem., Int. Ed., 2007, 46, 5056.
2010, 3, 811; (b) F. Cherubini, Energy Convers. Manage., 2010, 17 (a) B. M. Bhanage, S. Fujita, Y. Ikushima and M. Arai, Green
51, 1412; (c) A. Uihlein and L. Schebek, Biomass Bioenergy,
2009, 33, 793; (d) Y. G. Zheng, X. L. Chen and Y. C. Shen,
Chem. Rev., 2008, 108, 5253; (e) T. R. Brown and
R. C. Brown, RSC Adv., 2013, 3, 5758; (f) Z. Zhang, B. Du,
Chem., 2004, 6, 78; (b) S. Pulla, V. Unnikrishnan, P. Ramidi,
S. Z. Sullivan, A. Ghosh, J. L. Dallas and P. Munshi, J. Mol.
Catal. A: Chem., 2011, 338, 33.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 39020–39029 | 39029