Pd(II)-catalyzed synthesis of benzisoxazolones from benzohydroxamic acids via C-H activation

Article abstract of DOI:10.1021/jo301180k

A Pd-catalyzed method for the synthesis of benzisoxazolones from benzohydroxamic acids using Oxone as an oxidant in a one-pot procedure has been developed. In this process, the reaction appears to be suitable for construction of various benzisoxazolones.

Full text of DOI:10.1021/jo301180k

Note
pubs.acs.org/joc
Pd(II)-Catalyzed Synthesis of Benzisoxazolones from
Benzohydroxamic Acids via C−H Activation
Xi-Ai Gao, Ru-Long Yan,* Xian-Xue Wang, Hao Yan, Jian Li, Han Guo, and Guo-Sheng Huang*
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Key Laboratory of Nonferrous Metal Chemistry and
Resources Utilization of Gansu Province, Lanzhou 730000, People’s Republic of China
S
* Supporting Information
ABSTRACT: A Pd-catalyzed method for the synthesis of
benzisoxazolones from benzohydroxamic acids using Oxone as
an oxidant in a one-pot procedure has been developed. In this
process, the reaction appears to be suitable for construction of
various benzisoxazolones.
he ubiquity of heterocycles in biologically active molecules
has provided a driving force for chemists to develop
Lewis acids such as ZnCl2, AlCl3, and NiCl2 and organic acid
pivalic acid (PivOH) were employed as additives, the
combination of ZnCl2 and PivOH was proven to be highly
effective and resulted in 89% yield (Table 1, entry 16). Yield
decreased when temperature changed to 80 or 25 °C (Table 1,
entries 17 and 18). In addition, in the absence of palladium, no
target product was obtained (Table 1, entry 19). Furthermore,
changing the loading of Oxone and PivOH/ZnCl2 did not
improve the yield (Table 1, entries 20−23). As a result,
optimized conditions were identified, which provided 2a in
good yield (Table 1, entry 16).
Using the optimized conditions, we extended the scope of
the reaction, and the results are summarized in Table 2.
Generally, the reaction of benzohydroxamic acids proceeded
smoothly and afforded the corresponding benzisoxazolones 2 in
moderate to good yields. Satisfactorily, a variety of substituted
benzohydroxamic acids gave corresponding products 2a−2r.
The electron-rich benzohydroxamic acids showed better
reactivity and achieved higher yields than electron-deficient
ones (52−94% for 2b−2k vs 35−71% for 2m−2r). Further
investigations demonstrated that N-hydroxy-3,5-dimethylben-
zamide (1l) gave much lower yield than N-hydroxy-3-
methylbenzamide (1c) due to steric hindrance.
T
increasingly efficient methods toward their preparation.1
Among the many ring-forming reactions in heterocycle
synthesis, transition-metal-catalyzed C−H activation,2 partic-
ularly, Pd-catalyzed C−H activation, has become one of the
important methods to construct many heterocyclic molecules
in recent years.3
Isoxazolones are important heterocycles, not only because of
the significant pharmaceutical and therapeutic properties, such
as hypoglycemic, immunosuppressive, anti-inflammatory, and
antibacterial activities,4 but because they can also serve as
versatile building blocks in organic synthesis.5 Consequently,
isoxazolones have attracted considerable interests from
chemists and stimulated the development of numerous
methods for their synthesis.6 Recently, several new approaches
have been reported for the construction of benzisoxazolones
using nitrobenzoates7 and 2-nitrophenylacetylene.8 However,
there are very few general methods that convert easily available
materials in one step to substituted benzisoxazolones. Herein,
we wish to report a suitable and efficient method for the
preparation of functionalized benzisoxazolones from a variety of
benzohydroxamic acids by Pd-catalyzed reaction using Oxone
as oxidant.
Initially, we examined the reaction of N-hydroxybenzamide
(1a) with Oxone in N,N-dimethylacetamide (DMA) catalyzed
by Pd(OAc)2 at 45 °C (Table 1, entry 1). Gratifyingly, the
desired 1-benzoylbenzo[c]isoxazol-3(1H)-one (2a) was ob-
tained in 42% yield after 4 h. Several additional oxidants were
then evaluated, and results showed that Oxone was superior to
K2S2O8, tert-butyl hydroperoxide (TBHP), 1,4-benzoquinone
(BQ), and iodobenzene diacetate (PIDA) (Table 1, entries 2−
5). Thus, Oxone was chosen as the oxidant for further
optimization. Among the Pd sources we examined, Pd(OAc)2
showed the highest activity for this reaction (Table 1, entries
6−8). Moreover, the use of DMF, DMSO, and N-methyl-2-
pyrrolidone (NMP) did not improve the yield of the product
relative to DMA (Table 1, entries 9−11). To our delight, when
Additionally, the desired 3-(1-naphthoyl)naphtho[2,1-c]-
isoxazol-1(3H)-one (2s) from N-hydroxy-1-naphthamide (1s)
was obtained in 55% yield (eq 1).
It is worth mentioning that the reaction of N-hydroxy-1-
methyl-1H-indole-3- carboxamide (1t) gave unexpected prod-
uct 1-methylindoline-2,3-dione (2t) under the optimal
condition in 75% yield (eq 2). The structure of 2t was
unambiguously confirmed through single-crystal X-ray anal-
ysis.9
In order to gain insight into the reaction mechanism, an
additional experiment was performed. N-(Benzoyloxy)-
benzamide (3) as substrate under the optimal condition
Received: June 7, 2012
Published: August 16, 2012
© 2012 American Chemical Society
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The Journal of Organic Chemistry
Note
promoted by PivOH and ZnCl2,2h,11 followed by oxidation of
the Pd(II) intermediate 4 to the Pd(IV) intermediate 5.
Subsequently, benzohydroxamic acid 1 attacks intermediate 5
to give the intermediate 6. Then carbon−heteroatom bond
formation via reductive elimination affords compound 7.
Meanwhile, Pd(II) oxidized to Pd(IV) enters the next catalytic
cycle. In the final step, intermediate 7 undergoes intramolecular
nucleophilic addition and subsequent elimination to afford
product 2.
In conclusion, we have developed a direct Pd-catalyzed
method for the synthesis of benzisoxazolones from benzohy-
droxamic acids using Oxone as oxidation agent in a one-pot
manner, involving the cleavage of a C−H bond and the
formation of a C−N bond. A variety of substituents are
tolerated in this reaction, which proceeds smoothly in moderate
to good yields.
a
Table 1. Optimization of the Reaction Condition
temp
(°C)
yield
(%)
entry
catalyst
oxidant
additive
solvent
1
2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PdCl2
Oxone
K2S2O8
TBHP
BQ
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMF
DMSO
NMP
DMA
DMA
DMA
DMA
DMA
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
45
42
20
trace
0
3
4
5
PIDA
0
6
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
28
10
0
7
Pd(dba)2
Pd(PPh3)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
8
EXPERIMENTAL SECTION
General Methods. All reactions were performed in a test tube
■
9
22
0
10
11
12
13
14
15
16
under air. Column chromatography was performed using silica gel
30
45
0
1
(200−400 mesh). H NMR and 13C NMR spectra were recorded on
ZnCl2
AlCl3
400 MHz in DMSO-d6 and CDCl3 using TMS as the internal standard.
IR spectra were recorded on a FT-IR spectrometer, and only major
peaks are reported in cm−1. All new compounds were further
characterized by HRMS (ESI), and the mass analyzer type used for the
NiCl2
PivOH
0
10
89
1
HRMS was FT; copies of all H NMR and 13C NMR spectra are
PivOH/
ZnCl2
provided in the Supporting Information. All melting points were
determined without correction. Commercially available reagents and
solvents were used without further purification.
17
Pd(OAc)2
Pd(OAc)2
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
Oxone
PivOH/
ZnCl2
DMA
DMA
DMA
DMA
DMA
DMA
DMA
80
25
45
45
45
45
45
70
40
0
f
18
PivOH/
ZnCl2
Typical Procedure for the Preparation of Benzisoxazolones
2. A test tube was charged with 1 (0.3 mmol), Pd(OAc)2 (0.015
mmol), Oxone (0.3 mmol), and PivOH (0.6 mmol)/ZnCl2 (0.15
mmol). Then 1.5 mL of DMA was added to the reaction system. The
reaction was stirred at 45 °C for 4 h under air. After being cooled to
room temperature, the solvent was diluted with 10 mL of ethyl acetate,
washed with 5 mL of brine, and dried over anhydrous Na2SO4. After
the solvent was evaporated in vacuo, the residues were purified by
column chromatography (SiO2), eluting with petroleum ether/EtOAc
to afford pure 2.
19
PivOH/
ZnCl2
b
20
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PivOH/
ZnCl2
87
61
53
65
c
21
PivOH/
ZnCl2
d
22
PivOH/
ZnCl2
e
23
PivOH/
ZnCl2
1-Benzoylbenzo[c]isoxazol-3(1H)-one 2a: White solid (31.9
1
mg, 89%); mp 140−142 °C; H NMR (400 MHz, CDCl3) δ 8.26−
a
Unless otherwise specified, all reactions were carried out with 1a (0.3
mmol), catalyst (0.015 mmol), oxidant (0.3 mmol), PivOH (0.6
mmol)/ZnCl2 (0.15 mmol), solvent (1.5 mL), 4 h. PivOH (0.9
mmol)/ZnCl2 (0.15 mmol). PivOH (0.3 mmol)/ZnCl2 (0.15 mmol).
8.24 (d, J = 8.4 Hz, 1H), 8.00−7.98 (d, J = 7.6 Hz, 2H), 7.95−7.93 (d,
J = 7.6 Hz, 1H), 7.86−7.82 (m, 1H), 7.64−7.60 (t, J = 7.2 Hz, 1H),
7.55−7.51 (m, 2H), 7.47−7.43 (t, J = 7.6 Hz, 1H); 13C NMR (400
MHz, CDCl3) δ 164.0, 163.7, 145.8, 136.5, 132.9, 131.1, 129.7, 128.4,
126.0, 125.6, 115.8, 111.7; IR (neat, cm−1) 1785, 1679, 1465, 1366,
1331, 1252, 1069, 973, 752, 698, 674; HRMS (ESI) calcd for
C14H10NO3 [M + H]+ 240.0661, found 240.0656.
b
c
d
e
f
Oxone (0.15 mmol). Oxone (0.45 mmol). For 10 h.
6-Methyl-1-(4-methylbenzoyl)benzo[c]isoxazol-3(1H)-one
1
2b: White solid (36.8 mg, 92%); mp 162−164 °C; H NMR (400
MHz, CDCl3) δ 8.06 (s, 1H), 7.92−7.90 (d, J = 8.0 Hz, 2H), 7.81−
7.79 (d, J = 8.0 Hz, 1H), 7.33−7.31 (d, J = 8.0 Hz, 2H), 7.25−7.23 (d,
J = 8.0 Hz, 1H), 2.57 (s, 3H), 2.45 (s, 3H); 13C NMR (400 MHz,
CDCl3) δ 164.0, 163.8, 148.5, 146.4, 143.8, 129.8, 129.1, 128.3, 127.5,
125.1, 115.6, 109.2, 22.5, 21.6; IR (neat, cm−1) 1787, 1770, 1684,
1607, 1437, 1354, 1326, 1263, 1183, 1065, 1028, 977, 915, 823, 765,
730, 671; HRMS (ESI) calcd for C16H14NO3 [M + H]+ 268.0974,
found 268.0976.
5-Methyl-1-(3-methylbenzoyl)benzo[c]isoxazol-3(1H)-one
1
2c: White solid (36.4 mg, 91%); mp 126−128 °C; H NMR (400
MHz, CDCl3) δ 8.12−8.10 (d, J = 8.4 Hz, 1H), 7.78−7.74 (m, 2H),
7.71−7.70 (d, J = 0.8 Hz, 1H), 7.65−7.63 (dd, J = 1.2 Hz, J = 8.4 Hz,
1H), 7.43−7.38 (m, 2H), 2.49 (s, 3H), 2.44 (s, 3H); 13C NMR (400
MHz, CDCl3) δ 164.1, 163.9, 144.1, 138.2, 137.8, 136.3, 133.6, 131.2,
130.0, 128.2, 126.8, 124.8, 115.5, 111.8, 21.3, 21.0; IR (neat, cm−1)
1798, 1676, 1490, 1365, 1326, 1266, 1150, 1046, 975, 873, 822, 715;
HRMS (ESI) calcd for C16H14NO3 [M + H]+ 268.0974, found
268.0978.
could not cyclize to 2a, thus ruling out the intermediacy of 3 in
the formation of 2a (Scheme 1).
On the basis of the results obtained above, a plausible
reaction mechanism has been proposed (Scheme 2).
Palladation of benzohydroxamic acid 1 with Pd(OAc)2
produces five-membered palladacycle 4,10 which could be
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Note
a
Table 2. Synthesis of Benzisoxazolones from Benzohydroxamic Acids
a
Reaction conditions: 1 (0.3 mmol), Pd(OAc)2 (0.015 mmol), Oxone (0.3 mmol), PivOH (0.6 mmol)/ZnCl2 (0.15 mmol), 1.5 mL of DMA, in an
open tube, 45 °C, 4 h.
MHz, CDCl3) δ 8.06−8.02 (m, 2H), 7.78−7.76 (d, J = 8.8 Hz, 1H),
7.70−7.69 (d, J = 2.4 Hz, 1H), 7.02−6.98 (m, 2H), 6.96−6.93 (dd, J =
2.0 Hz, J = 8.8 Hz, 1H), 3.97 (s, 3H), 3.90 (s, 3H); 13C NMR (400
MHz, CDCl3) δ 166.7, 163.6, 163.4, 148.5, 132.2, 126.5, 123.1, 115.9,
113.8, 103.9, 98.2, 56.2, 55.5; IR (neat, cm−1) 1765, 1678, 1619, 1601,
1489, 1453, 1289, 1263, 1174, 1101, 1023, 981, 911, 845, 830, 748,
676, 622; HRMS (ESI) calcd for C16H14NO5 [M + H]+ 300.0872,
found 300.0875.
Scheme 1. Attempted Pd-Catalyzed Cyclization of 3
5-Methoxy-1-(3-methoxybenzoyl)benzo[c]isoxazol-3(1H)-
6-Methoxy-1-(4-methoxybenzoyl)benzo[c]isoxazol-3(1H)-
one 2d: White solid (32.7 mg, 73%); mp 158−160 °C; 1H NMR (400
one 2e: White solid (23.3 mg, 52%); mp 124−126 °C; 1H NMR (400
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Note
Scheme 2. Proposed Reaction Mechanism
MHz, CDCl3) δ 8.14−8.12 (d, J = 9.2 Hz, 1H), 7.58−7.56 (d, J = 7.6
Hz, 1H), 7.46 (s, 1H), 7.44−7.40 (m, 2H), 7.29−7.28 (d, J = 2.4 Hz,
1H), 7.16−7.13 (dd, J = 2.4 Hz, J = 8.4 Hz, 1H), 3.89 (s, 3H), 3.87 (s,
3H); 13C NMR (400 MHz, CDCl3) δ 163.8, 163.5, 159.4, 158.1,
140.6, 132.3, 129.4, 126.3, 122.0, 119.1, 117.1, 114.5, 112.6, 105.6,
55.9, 55.4; IR (neat, cm−1) 1784, 1667, 1594, 1491, 1344, 1277, 1254,
1140, 1061, 1021, 992, 911, 874, 824, 791, 740, 683; HRMS (ESI)
calcd for C16H14NO5 [M + H]+ 300.0872, found 300.0877.
7.00 (dd, J = 2.0 Hz, J = 8.8 Hz, 1H), 5.21 (s, 2H), 5.16 (s, 2H); 13C
NMR (400 MHz, CDCl3) δ 165.8, 163.6, 163.5, 162.7, 148.5, 136.1,
135.4, 132.3, 128.8, 128.8, 128.6, 128.3, 127.8, 127.5, 126.7, 123.5,
116.3, 114.7, 104.2, 99.4, 71.0, 70.3; IR (neat, cm−1) 1776, 1667, 1604,
1490, 1449, 1378, 1335, 1284, 1258, 1177, 1091, 1071, 981, 912, 839,
737, 697, 654; HRMS (ESI) calcd for C28H22NO5 [M + H]+ 452.1498,
found 452.1493.
6-Fluoro-1-(4-fluoro-2-methylbenzoyl)-4-methylbenzo[c]-
isoxazol-3(1H)-one 2j: White solid (31.2 mg, 68%); mp 128−130
1-([1,1′-Biphenyl]-4-carbonyl)-6-phenylbenzo[c]isoxazol-
1
1
3(1H)-one 2f: White solid (45.1 mg, 77%); mp 190−192 °C; H
°C; H NMR (400 MHz, CDCl3) δ 7.73−7.70 (m, 1H), 7.54−7.50
NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.11−8.09 (d, J = 8.4 Hz,
2H), 7.98−7.96 (d, J = 8.0 Hz, 1H), 7.75−7.64 (m, 7H), 7.53−7.40
(m, 6H); 13C NMR (400 MHz, CDCl3) δ 163.8, 163.6, 150.1, 146.5,
145.8, 139.7, 139.1, 130.4, 129.7, 129.13, 129.10, 128.9, 128.3, 127.7,
127.3, 127.0, 125.8, 125.6, 113.9, 110.3; IR (neat, cm−1) 1780, 1672,
1608, 1423, 1363, 1264, 1072, 973, 898, 738, 695; HRMS (ESI) calcd
for C26H18NO3 [M + H]+ 392.1287, found 392.1289.
(m, 1H), 7.02−6.98 (m, 2H), 6.93−6.91 (dd, J = 1.6 Hz, J = 9.6 Hz,
1H), 2.68 (s, 3H), 2.43 (s, 3H); 13C NMR (400 MHz, CDCl3) δ
168.9, 165.9 (d, JC−F = 324 Hz), 163.8, 163.0 (d, JC−F = 132 Hz), 146.8
(d, JC−F = 64 Hz), 143.2 (d, JC−F = 44 Hz), 140.6 (d, JC−F = 36 Hz),
130.8 (d, JC−F = 36 Hz), 127.6, 118.1 (d, JC−F = 84 Hz), 115.8 (d, JC−F
= 100 Hz), 113.1 (d, JC−F = 88 Hz), 106.5, 100.5 (d, JC−F = 116 Hz),
19.9, 17.6; IR (neat, cm−1) 1779, 1689, 1606, 1588, 1539, 1493, 1444,
1423, 1367, 1339, 1306, 1281, 1235, 1180, 1134, 1101, 1032, 991, 961,
923, 863, 813, 751, 669, 621; HRMS (ESI) calcd for C16H12F2NO3 [M
+ H]+ 304.0785, found 304.0788.
6-Ethyl-1-(4-ethylbenzoyl)benzo[c]isoxazol-3(1H)-one 2g:
1
Colorless liquid (36.3 mg, 82%); H NMR (400 MHz, CDCl3) δ
8.08 (s, 1H), 7.93−7.91 (d, J = 8.4 Hz, 2H), 7.83−7.81 (d, J = 8.0 Hz,
1H), 7.35−7.33 (d, J = 8.4 Hz, 2H), 7.28 (s, 1H), 2.87−2.82 (q, J = 7.6
Hz, 2H), 2.77−2.71 (m, 2H), 1.35−1.31 (t, J = 7.6 Hz, 3H), 1.30−
1.26 (t, J = 7.6 Hz, 3H); 13C NMR (400 MHz, CDCl3) δ 164.0, 163.8,
154.7, 149.9, 146.5, 129.9, 128.6, 127.9, 126.4, 125.2, 114.6, 109.4,
29.8, 28.9, 15.2, 15.1; IR (neat, cm−1) 1783, 1674, 1610, 1441, 1416,
1362, 1334, 1260, 1187, 1073, 984, 967, 907, 842, 748, 681; HRMS
(ESI) calcd for C18H18NO3 [M + H]+ 296.1287, found 296.1283.
6-Isopropyl-1-(4-isopropylbenzoyl)benzo[c]isoxazol-3(1H)-
one 2h: Colorless liquid (45.5 mg, 94%); 1H NMR (400 MHz,
CDCl3) δ 8.10 (s, 1H), 7.94−7.92 (dd, J = 1.6 Hz, J = 6.8 Hz, 2H),
7.84−7.82 (d, J = 8.0 Hz, 1H), 7.38−7.36 (d, J = 8.4 Hz, 2H), 7.32−
7.29 (dd, J = 1.2 Hz, J = 8.0 Hz, 1H), 3.17−3.06 (m, 1H), 3.05−2.95
(m, 1H), 1.35 (s, 3H), 1.33 (s, 3H), 1.30 (s, 3H), 1.29 (s, 3H); 13C
NMR (400 MHz, CDCl3) δ 164.0, 163.8, 159.3, 154.4, 146.6, 129.9,
128.8, 126.5, 125.3, 125.1, 113.3, 109.5, 35.2, 34.3, 23.6; IR (neat,
cm−1) 1783, 1675, 1610, 1440, 1416, 1346, 1261, 1189, 1055, 978,
918, 878, 842, 741, 689; HRMS (ESI) calcd for C20H22NO3 [M + H]+
324.1600, found 324.1605.
6-Benzoyl-1-(4-benzoylbenzoyl)benzo[c]isoxazol-3(1H)-one
1
2k: White solid (41.3 mg, 61%); mp 142−144 °C; H NMR (400
MHz, CDCl3) δ 8.58 (s, 1H), 8.10−8.07 (m, 3H), 7.94−7.92 (d, J =
8.4 Hz, 2H), 7.88−7.83 (m, 5H), 7.69−7.62 (m, 2H), 7.57−7.51 (dd, J
= 7.6 Hz, J = 15.6 Hz, 4H); 13C NMR (400 MHz, CDCl3) δ 195.5,
194.7, 163.2, 162.7, 145.6, 145.3, 141.5, 136.7, 136.0, 133.8, 133.7,
133.1, 130.2, 130.1, 129.7, 129.6, 128.7, 128.5, 127.1, 125.9, 116.9,
113.9; IR (neat, cm−1) 1788, 1664, 1613, 1596, 1502, 1431, 1404,
1361, 1321, 1274, 1234, 1181, 1072, 989, 923, 857, 798, 729, 703, 663;
HRMS (ESI) calcd for C28H18NO5 [M + H]+ 448.1185, found
448.1183.
1-(3,5-Dimethylbenzoyl)-5,7-dimethylbenzo[c]isoxazol-
1
3(1H)-one 2l: White solid (24.3 mg, 55%); mp 120−122 °C; H
NMR (400 MHz, CDCl3) δ 7.61 (s, 2H), 7.52 (s, 1H), 7.45 (s, 1H),
7.26 (s, 1H), 2.45 (s, 3H), 2.44 (s, 3H), 2.40 (s, 6H); 13C NMR (400
MHz, CDCl3) δ 168.4, 165.6, 146.1, 139.4, 138.2, 137.3, 135.3, 131.6,
128.2, 127.5, 122.5, 114.5, 21.3, 20.9, 19.9; IR (neat, cm−1) 1786,
1698, 1603, 1492, 1307, 1266, 1193, 1093, 1024, 885, 863, 763, 733,
679; HRMS (ESI) calcd for C18H18NO3 [M + H]+ 296.1287, found
296.1285.
6-(Benzyloxy)-1-(4-(benzyloxy)benzoyl)benzo[c]isoxazol-
1
3(1H)-one 2i: White solid (49.1 mg, 72%); mp 146−148 °C; H
NMR (400 MHz, CDCl3) δ 8.03−8.01 (d, J = 8.8 Hz, 2H), 7.80−7.76
(m, 2H), 7.47−7.33 (m, 10H), 7.08−7.06 (d, J = 8.8 Hz, 2H), 7.02−
5-Fluoro-1-(3-fluorobenzoyl)benzo[c]isoxazol-3(1H)-one
1
2m: White solid (27.6 mg, 67%); mp 160−162 °C; H NMR (400
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MHz, CDCl3) δ 8.04−8.02 (d, J = 8.4 Hz, 1H), 7.85−7.80 (m, 1H),
7.65−7.56 (m, 2H), 7.32−7.28 (m, 1H), 7.24−7.20 (t, J = 9.2 Hz,
1H), 7.11−7.07 (t, J = 8.4 Hz, 1H); 13C NMR (400 MHz, CDCl3) δ
1658, 1447, 1335, 1229, 1052, 1026, 1005, 824, 762, 624; HRMS
(ESI) calcd for C22H14NO3 [M + H]+ 340.0974, found 340.0978.
1-Methylindoline-2,3-dione 2t: Yellow solid (36.2 mg, 75%);
mp 120−122 °C; 1H NMR (400 MHz, CDCl3) δ 7.63−7.59 (m, 2H),
7.15−7.11 (m, 1H), 6.91−6.89 (d, J = 8.0 Hz, 1H), 3.26 (s, 3H); 13C
NMR (400 MHz, CDCl3) δ 183.3, 158.2, 151.4, 138.3, 125.2, 123.8,
117.4, 109.8, 26.2; IR (neat, cm−1) 1743, 1726, 1606, 1467, 1366,
1325, 1253, 1190, 1157, 1112, 1089, 1035, 954, 862, 814, 754, 700;
HRMS (ESI) calcd for C9H8NO2 [M + H]+ 162.0555, found
162.0557.
160.7 (d, JC−F = 172 Hz), 159.5, 157.6, 156.2, 146.0, 139.0 (d, JC−F
=
32 Hz), 134.2 (d, JC−F = 36 Hz), 130.0, 124.4 (d, JC−F = 12 Hz), 120.4
(d, JC−F = 56 Hz), 116.6 (d, JC−F = 84 Hz), 112.5 (d, JC−F = 72 Hz),
111.2 (d, JC−F = 20 Hz), 101.4; IR (neat, cm−1) 1787, 1685, 1627,
1610, 1493, 1453, 1369, 1330, 1299, 1258, 1185, 1148, 1005, 970, 797,
774, 668; HRMS (ESI) calcd for C14H8F2NO3 [M + H]+ 276.0472,
found 276.0475.
1
N-(Benzoyloxy)benzamide 3: H NMR (400 MHz, CDCl3) δ
6-Fluoro-1-(4-fluorobenzoyl)benzo[c]isoxazol-3(1H)-one 2n:
1
9.76 (s, 1H), 8.17−8.14 (m, 2H), 7.88−7.86 (m, 2H), 7.67−7.63 (m,
1H), 7.60−7.57 (m, 1H), 7.52−7.46 (m, 4H); 13C NMR (400 MHz,
CDCl3) δ 166.5, 165.2, 134.3, 132.8, 130.8, 130.0, 128.8, 128.7, 127.5,
126.5.
White solid (29.3 mg, 71%); mp 132−134 °C; H NMR (400 MHz,
CDCl3) δ 8.08−8.03 (m, 2H), 7.96−7.92 (m, 2H), 7.24−7.14 (m,
3H); 13C NMR (400 MHz, CDCl3) δ 169.2, 166.9 (d, JC−F = 124 Hz),
164.4, 162.7 (d, JC−F = 48 Hz), 147.3 (d, JC−F = 60 Hz), 132.7 (d, JC−F
= 40 Hz), 127.9 (d, JC−F = 44 Hz), 126.7, 115.9 (d, JC−F = 88 Hz),
115.1 (d, JC−F = 100 Hz), 107.8, 103.5 (d, JC−F = 120 Hz); IR (neat,
cm−1) 1791, 1684, 1602, 1506, 1483, 1450, 1412, 1367, 1335, 1279,
1249, 1162, 1065, 984, 927, 842, 760, 668, 618; HRMS (ESI) calcd for
C14H8F2NO3 [M + H]+ 276.0472, found 276.0478.
ASSOCIATED CONTENT
* Supporting Information
■
S
Spectral data for all new compounds, and X-ray data for 2t, in
CIF format. This material is available free of charge via the
Internet at http://pubs.acs.org.
4-Chloro-1-(2-chlorobenzoyl)benzo[c]isoxazol-3(1H)-one
1
2o: White solid (25.2 mg, 55%); mp 152−154 °C; H NMR (400
MHz, CDCl3) δ 8.16−8.14 (d, J = 8.0 Hz, 1H), 7.78−7.74 (t, J = 8.0
Hz, 1H), 7.54−7.50 (m, 3H), 7.43−7.39 (m, 2H); 13C NMR (400
MHz, CDCl3) δ 161.7, 160.5, 145.8, 137.5, 133.3, 132.4, 131.9, 131.6,
130.1, 129.0, 127.1, 126.9, 113.3, 109.5; IR (neat, cm−1) 1794, 1694,
1596, 1475, 1436, 1360, 1321, 1228, 1060, 970, 792, 765, 736, 663,
641; HRMS (ESI) calcd for C14H8Cl2NO3 [M + H]+ 307.9881, found
307.9885.
AUTHOR INFORMATION
Corresponding Author
*E-mail: hgs@lzu.edu.cn. yanrl@lzu.edu.cn.
Notes
■
The authors declare no competing financial interest.
5-Chloro-1-(3-chlorobenzoyl)benzo[c]isoxazol-3(1H)-one
1
2p: White solid (23.4 mg, 51%); mp 115−116 °C; H NMR (400
ACKNOWLEDGMENTS
■
MHz, CDCl3) δ 8.21−8.19 (d, J = 8.8 Hz, 1H), 7.94 (s, 1H), 7.91−
7.90 (d, J = 1.6 Hz, 1H), 7.88−7.86 (d, J = 8.0 Hz, 1H), 7.81−7.78
(dd, J = 2.0 Hz, J = 8.8 Hz, 1H), 7.61−7.59 (d, J = 8.4 Hz, 1H), 7.49−
7.45 (t, J = 8.0 Hz, 1H); 13C NMR (400 MHz, CDCl3) δ 162.4, 162.1,
144.0, 137.0, 134.7, 133.2, 132.3, 132.1, 129.8, 129.7, 127.8, 125.1,
117.1, 113.1; IR (neat, cm−1) 1789, 1669, 1463, 1362, 1315, 973, 909,
829, 736, 674, 651; HRMS (ESI) calcd for C14H8Cl2NO3 [M + H]+
307.9881, found 307.9883.
We thank the Fundamental Research Funds for the Central
Universities (lzujbky-2012-74) for financial support.
REFERENCES
■
(1) (a) Li, J.-J., Corey, E. J., Eds. Name Reactions in Heterocyclic
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6-Chloro-1-(4-chlorobenzoyl)benzo[c]isoxazol-3(1H)-one
1
2q: White solid (19.3 mg, 42%); mp 130−132 °C; H NMR (400
MHz, CDCl3) δ 8.29 (s, 1H), 7.96−7.94 (d, J = 8.4 Hz, 2H), 7.87−
7.85 (d, J = 8.4 Hz, 1H), 7.52−7.50 (d, J = 8.4 Hz, 2H), 7.44−7.42 (d,
J = 8.4 Hz, 1H); 13C NMR (400 MHz, CDCl3) δ 162.8, 162.5, 146.2,
143.5, 139.9, 131.2, 128.9, 127.1, 126.6, 116.0, 110.0; IR (neat, cm−1)
1792, 1742, 1679, 1606, 1590, 1462, 1434, 1404, 1364, 1317, 1260,
1183, 1092, 1066, 1017, 978, 900, 863, 833, 804, 732, 665; HRMS
(ESI) calcd for C14H8Cl2NO3 [M + H]+ 307.9881, found 307.9887.
4-Chloro-1-(2-chloro-4-fluorobenzoyl)-6-fluorobenzo[c]-
isoxazol-3(1H)-one 2r: White solid (18.2 mg, 35%); mp 130−132
1
°C; H NMR (400 MHz, CDCl3) δ 7.90−7.87 (m, 1H), 7.56−7.53
(dd, J = 5.6 Hz, J = 8.4 Hz, 1H), 7.27−7.25 (m, 1H), 7.19−7.12 (m,
2H); 13C NMR (400 MHz, CDCl3) δ 168.8, 165.8 (d, JC−F = 332 Hz),
162.8, 160.3 (d, JC−F = 592 Hz), 146.7 (d, JC−F = 64 Hz), 135.3 (d,
JC−F = 56 Hz), 133.6 (d, JC−F = 40 Hz), 131.0 (d, JC−F = 40 Hz), 127.7
(d, JC−F = 16 Hz), 118.1 (d, JC−F = 100 Hz), 116.3 (d, JC−F = 112 Hz),
114.7 (d, JC−F = 88 Hz), 106.0, 101.4 (d, JC−F = 116 Hz); IR (neat,
cm−1) 1802, 1703, 1601, 1538, 1483, 1425, 1363, 1335, 1290, 1264,
1215, 1176, 1110, 1077, 1046, 995, 952, 913, 857, 800, 735, 659, 620;
HRMS (ESI) calcd for C14H6Cl2F2NO3 [M + H]+ 343.9693, found
343.9697.
3-(1-Naphthoyl)naphtho[2,1-c]isoxazol-1(3H)-one 2s: Lilac
solid (27.9 mg, 55%); mp 200−202 °C; 1H NMR (400 MHz,
DMSO-d6) δ 8.61−8.59 (d, J = 8.0 Hz, 1H), 8.55−8.53 (d, J = 8.8 Hz,
1H), 8.25−8.18 (m, 3H), 8.12−8.07 (m, 2H), 8.03−8.01 (d, J = 7.2
Hz, 1H), 7.89−7.85 (m, 1H), 7.74−7.70 (m, 2H), 7.66−7.60 (m, 2H);
13C NMR (400 MHz, DMSO-d6) δ 163.16, 163.13, 146.0, 138.6,
132.9, 131.9, 130.5, 130.3, 129.4, 129.2, 128.5, 127.7, 127.6, 127.5,
126.9, 126.7, 124.9, 124.6, 121.7, 113.3, 103.7; IR (neat, cm−1) 1783,
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NOTE ADDED AFTER ASAP PUBLICATION
■
After ASAP publication on August 23, 2012, references 3j and
3k were added and this paper reposted ASAP on August 28,
2012.
7705
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