Synthesis of 2-methylbenzoxazoles directly from: N -phenylacetamides catalyzed by palladium acetate

Article abstract of DOI:10.1039/c7ob02566a

A method to synthesize 2-methylbenzoxazoles directly from N-phenylacetamides catalyzed by Pd(OAc)₂ in the presence of K₂S₂O₈ and TfOH has been developed. The desired products were obtained in moderate to excellent yields. This approach provides a facile procedure to prepare benzoxazoles with available substrates. It is found that TfOH is the key factor for this cyclization reaction. A plausible mechanism of the reaction is proposed according to the control reactions and the literature.

Full text of DOI:10.1039/c7ob02566a

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
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Synthesis of 2-Methylbenzoxazoles Directly from N-
phenylacetamides Catalyzed by Palladium Acetate
Received 00th January 20xx,
Accepted 00th January 20xx
Biying Wang, Chengfei Jiang, Jiasheng Qian, Shuwei Zhang*, Xiaodong Jia, Yu Yuan*
DOI: 10.1039/x0xx00000x
A method to synthesize 2-methylbenzoxazoles directly from N-phenylacetamides catalyzed by Pd(OAc)
2
in the presence of
2 2 8
K S O
and TfOH. The desired products were obtained in moderate to excellent yields. This approach provides a facile
www.rsc.org/
procedure to prepare benzoxazoles with available substrates. It is found that TfOH is the key factor for this cyclization
reaction. The plausible mechanism of the reaction is proposed according to the control reactions and the literatures.
available N-phenylacetamides.
Introduction
The construction of functionalized benzoxazoles has been
receiving considerable attention, since the benzoxazole moiety
as one of important subunits is widely present in natural
products and pharmaceutical compounds, as well as some
1
optical materials. A number of methods for preparation of
benzoxazoles have been developed in the past decades. The
classical approaches are the oxidative cyclization of the
compounds condensed from 2-aminophenols and aldehydes or
2
carboxylic acids. Some transition-metal-catalyzed C-N or C-O
coupling reactions have also been reported for synthesis of
benzoxazoles from intramolecular cyclization of halogenated
3
arene precusors. Although these methods provide available
access to benzoxazoles, there are still some limitations such as
substrate scopes, harsh reaction conditions, and low atom-
economy. To overcome these drawbacks, considerable efforts
has been devoted to develop new approaches for the
construction of C-O bonds via C-H functionalization processes.
For examples, C-H functionalization followed by C-O bond
formation has been explored for the synthesis of benzoxazoles
by using palladium-, ruthenium-, iron-, copper-based catalytic,
4
Scheme 1. Different pathways for the synthesis of 2-substituted arene
or organocatalytic systems. Among these researches, 2-aryl
derivatives.
substituted benzoxazole derivatives were synthesized with
corresponding aryl substrates in most cases. Unfortunately,
few examples were reported to prepare 2-alkyl substituted
benzoxazole derivatives from N-phenylacetamides (Scheme 1).
Recently, our group focused on the oxidative C-H bond
Results and discussion
5
a
According to our previous work , the combination of oxidant,
acid, and palladium could be affected the coordination of N-
phenylacetamide. Firstly, we used 2-acetamidophenyl acetate
5
coupling reactions of N-phenylacetamide and benzotholizoles.
Herein, we report a direct method to prepare 2-methyl
benzoxazoles by palladium-catalyzed C-H functinalization and
intramolecular oxidative C-O coupling reaction with readily
(
1a) as substrate to test the cyclization reaction in the
presence of and TsOH in the mixed solvents
AcOH/DMF) by using Pd(OAc) as catalyst to obtain 42% 2-
methylbenzo[d]oxazol-4-yl acetate (2a) (Table 1, entry 1). The
2 2 8
K S O
(
2
a. School of Chemistry and Chemical Engineering,Yangzhou University, 225002 yield improved to 64% with use of TfOH as additive (Table 1,
Yangzhou, People’s Republic of China.
entry 2), whereas 2a was not formed when TFA was in the
†
E-mail: shuweiz@yzu.edu.cn, yyuan@yzu.edu.cn
Electronic Supplementary Information (ESI) available: [details of any system (Table 1, entry 3). After adjusting the amount of TfOH,
supplementary information available should be included here]. See DOI:
the results indicated that 1.0 equiv of TfOH was optimal for the
1
0.1039/x0xx00000x
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reaction (Table 1, entries 2, 4-6). Other oxidants (TBHP, TBAI, as substrates to verify the scope of the reactions. The results
and O ) were also used to investigate the influence on the indicated that the reactions were mild and tolerated for many
reactions, but all failed. It was shown that the best oxidant is functional groups in good to mild yields (Table 2). While N-
2
1
.5 equiv potassium peroxodisulfate (Table 1, entries 4, 7-8).
phenylacetamide (1b) was carried out on the optimal
conditions, 2a was isolated rather than benzoxazole. We
proposed that the reaction should first form 2-
Table 1. Optimization of the Pd-catalyzed intramolecular oxidative C-O coupling
6
[a]
acetamidophenyl acetate, then it was cyclized via
reaction.
intramolecular oxidative C-O coupling reaction to get 2a. For
either mono- or di- halogen substrates, the reactions worked
well (2b
on the o-substituted compounds resulted in a lower yields (2g
). The stronger electron-withdrawing substitutions on the
-2d, 2r-2s). It is found that electron-donating moieties
-
2h
aromatic ring, the better yields were obtained, especially for
methyl 2-acetamidobenzoate whose yield reached to 89% (2f).
There is not obvious influence on the yields while multiple
Entry
Pd
Additive
(equiv.)
p-TsOH
Oxidants
(equiv.)
Solvent
Yields
[b]
(
10mol%)
(%)
1
2
Pd(OAc)
2
K
2
S
2
O
8
(2)
AcOH/DMF
AcOH/DMF
42
64
substituents on the ring, even containing methyl group (2i-2p).
(
0.5)
TfOH
0.5)
The best yield could reach to 93% which contained methyl and
ester groups (2p). However, when the methyl group connected
to carbonyl group was changed to ethyl or phenyl group, the
desired products were hardly detected.
Pd(OAc)
2
K
2
S
2
O
8
(2)
(
3
4
5
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
TFA
TfOH (1)
TfOH
K
K
K
2
2
2
S
S
S
2
2
2
O
O
O
8
8
8
(2)
(2)
(2)
AcOH/DMF
AcOH/DMF
AcOH/DMF
NR
66
55
Table 2. Pd-catalyzed intramolecular oxidative C-O coupling reaction with
[a]
(1.5)
different N-phenylacetamides.
6
7
8
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
TfOH (2)
TfOH (1)
TfOH (1)
K
K
2
2
S
S
2
2
O
O
8
8
(2)
(1)
AcOH/DMF
AcOH/DMF
AcOH/DMF
48
43
68
2 2 8
K S O
(1.5)
9
Pd(TFA)
Pd(PPh
2
TfOH
K
K
2
2
S
2
O
8
(2)
AcOH/DMF
AcOH/DMF
AcOH
47
23
(
0.5)
TfOH
0.5)
1
1
1
1
1
0
1
2
3
4
3 4
)
S
2
O
8
(2)
(
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
TfOH (1)
TfOH (1)
TfOH (1)
TfOH (1)
K
2
S
2
O
8
8
8
8
Trace
Trace
55
[
c]
2
2
a 68%
d 42%
2a 47%
2b 81%
2f 89%
2c 71%
(
1.5)
K
2
S
2
O
DMF
(
1.5)
[c]
K
2
S
2
O
AcOH/DMF
(
1.5)
[
d]
[d]
2e 74%
2g 28%
Pd(OAc)2
K
2
S
2
O
AcOH/DMF
47
(1.5)
[
a]
Unless otherwise specified, the reaction was carried out with 1a (0.2 mmol),
o
[b]
catalysts, additives and oxidants at 100 C in AcOH/DMF (8/1) for 24 h. Yields
[c]
[d]
after purification. AcOH/DMF (4/1). AcOH/DMF (10/1).
[d]
2
h 24%
2i 80%
2j 84%
2k 81%
The catalysts Pd(TFA) and Pd(PPh ) were also tested under
2 3 4
the conditions (Table 1, entries 9-10). A little lower yield of 2a
47%) was obtained by employing Pd(TFA) . When sole solvent
(
2
AcOH or DMF (Table 1, entries 11-12) was applied in the
reaction system, only few products were detected. It is evident
that the mixed solvents are necessary for the reaction. The
ratio of the mixed solvents also affected the reactions, and
AcOH/DMF (8/1) was suitable for the reactions (Table 1,
entries 13-14). As a result, the best result was achieved under
2
l 90%
2m 52%
2n 77%
2o 76%
these conditions including 10 mol% of Pd(OAc) as catalyst, 1.0
2
equiv TfOH as additive, 1.5 equiv of K S O as the oxidant, and
2
2 8
o
2p 93%
2q 62%
2r 58%
2s 41%
AcOH/DMF (8/1) as the solvent at 100 C.
With the optimal reaction condition, we further investigated
[
a]
Reaction conditions: 1a (0.2 mmol), Pd(OAc)
2
(0.02 mmol), K
S
2 2
O
8
(0.3 mmol),
o
[b]
[c]
the scope and functional group compatibility of the palladium- TfOH (0.2 mmol), CH COOH/DMF (8/1), 100 C, air. Yield after purification. N-
3
catalyzed intramolecular oxidative C-O coupling reaction. A
[d]
phenylacetamide as substrate.
Yields determined by NMR with 1,3,5-
variety of o-substituted N-phenylacetamides were employed
trimethoxybenzene as internal standard.
2
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Based on our results and reported works, a plausible
mechanism is proposed in Scheme 3. The reaction was
initiated by electrophilic attack of a Pd(II) center to the
aromatic ring with the assistance of the acetamino group to
7
form a bimetallic palladium complex. The Pd(II) intermediate
would undergo the oxidative addition to form Pd(IV) in the
8
. The anion species linked with Pd(IV)
presence of
K
2
S
2
O
8
-
could be the TfO anion that enhanced the catalytic reactivity,
-
since AcO coordinated with palladium could be replaced by
-
TfO in the system.
5a, 9
The acetyl group connected with amine
-
was transfered to enol formation since TfO promoted the
coordination of palladium with oxygen atom. After reductive
elimination the desired compound was produced, and Pd(II) was
regenerated for the cycle.
Scheme 2. Control experiments.
Scheme 3. Plausible mechanism for palladium catalyzed intramolecular oxidative
C-O coupling reaction.
Figure 1. The time history plot of the reaction of N-phenylacetamide
Conclusions
In Table 2, the same product 2a could be obtained using 1a In conclusion, we have developed an efficient and clean method to
and N-phenylacetamide, respectively. In order to investigate synthesize 2-methyl benzoxazoles from N-phenylacetamides by C-H
the reaction mechanism, some control reactions were carried functinalization and intramolecular oxidative C-O coupling reaction
out (Scheme 2). Firstly, 2-methylbenzo[d]oxazole was with catalytic amount of palladium(II) acetate. The reaction reveals
employed as substrate, whereas no reaction happened under high efficiency in atom-economy, and could be carried out in wide
the optimal conditions. Then, N-phenylacetamide was used, scope of substrates which are readily available.
and the process of this reaction was detected by HPLC at 3
hours interval. The results were shown in Figure 1. It was
found that the compound 1a was formed, and the maximum Experimental section
concentration of 1a was appeared at the 6 hour. Meanwhile,
th
1
. General information
in the first 3h, no desired product was formed in the system.
Interestingly, the product was found while 1a reached the high
concentration (6h). The substrate and 1a were almost
disappeared after 9h and 21h, respectively. In the whole
reaction, the doubly acetoxylated N-phenylacetamide was
never generated. It was suggested that N-phenylacetamide
first underwent an ortho-acetoxylation and then formed the
benzoxazole.
1
13
H NMR and C NMR spectra were obtained with a Agilent
3
Technologies 400 spectrometer in CDCl with TMS as an internal
standard. Chemical shifts (δ) are reported in ppm, and coupling
constants (J) are in Hertz (Hz). The following abbreviations were
used to explain the multiplicities: s = singlet, d = doublet, t = triplet,
q = quartet, m = multiplet, br = broad. Mass spectra were obtained
on a Bruker Dalton maXis instrument. All reactions were monitored
by TLC. Flash column chromatograph was carried out using 300-400
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mesh silica gel at medium pressure.
14.54; IR (KBr): ν = 2925, 2855, 1769, 1620, 1493, 1438, 1373, 1253,
-1
1
1
3
193, 1044, 866, 803, 743, 582 cm ; HRMS: Calculated for C10
92.0660, found: 192.0653.
9 3
H NO :
2. Preparation of starting materials
) 4-Chloro-2-methylbenzo[d]oxazole (2b)
In a 50 mL round bottom flask, aniline (5.0 mmol, 1.0 equiv) was
dissolved in 20 mL dichloromethane. Then, acetic anhydride (6.0
mmol, 1.2 equiv) was added and the reaction was stirred at room
temperature till complete consumption of anilines. After completion
of the reaction, the mixture was washed with a saturated solution
1
of sodium carbonate, the organic layer dried with Na
2
SO
4
and the Yield: 81%. White solid; Mp: 52 – 55 °C; H NMR (400 MHz, CDCl ) δ
3
solvent removed under reduced pressure to obtain the desired N- 7.34 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 7.9 Hz, 1H), 7.18 (t, J = 8.0 Hz,
1
3
phenylacetamide in quantative yield. In most cases, analytically 1H), 2.63 (s, 3H). C NMR (100 MHz, CDCl ) δ 164.63, 151.47,
3
pure N-phenylacetamides can be obtained after extraction however 139.20, 124.95, 124.31, 123.87, 108.86, 14.56; IR (KBr): ν = 3079,
if necessary purification by flash chromatography with ethyl acetate 2926, 2855, 1677, 1611, 1471, 1425, 1254, 1159, 1092, 1031, 946,
-
1
/
hexane was used.
866, 800, 146, 520 cm ; HRMS: Calculated for C H BrNO: 211.9711,
8 6
All other commercially available reagents were purchased from found: 211.9705.
commercial sources or preparation according to the literatures and 4) 4-Bromo-2-methylbenzo[d]oxazole (2c)
purified by standard techniques without special instructions.
Solvents were freshly dried and degassed according to the
purification handbook Purification of Laboratory Chemicals before
using.
1
Yield: 71%. White solid; Mp: 74 – 77°C; H NMR (600 MHz, CDCl
3
) δ
3
. General procedure for substrate scope
7
.46 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.16 (t, J = 8.0 Hz,
1
3
2
3
Pd(OAc) (4.5 mg, 0.02 mmol), 2-acetamidophenyl acetate 1a (38.6 1H), 2.66 (s, 3H). C NMR (150 MHz, CDCl ) δ 164.49, 151.08,
mg, 0.2 mmol), glacial acetic acid (0.8 mL), N,N-dimethylformamide 140.95, 127.48, 125.68, 111.96, 109.43, 14.45; IR (KBr): ν = 3556,
0.1 mL), potassium peroxodisulfate (100.0 mg, 0.3 mmol), and 3069, 2922, 2852, 1605, 1560, 1422, 1248, 1127, 1038, 916, 860,
(
-1
TfOH (30 mg, 0.2 mmol) were placed into a 15-mL sealed tube, and 790 cm ; HRMS: Calculated for C H BrNO: 211.9711, found:
8
6
o
heated in an oil bath at 100 C. The reaction was stirring for 24 h. 211.9705.
After cooling to room temperature, the reaction mixture was 5) 4-Iodo-2-methylbenzo[d]oxazole (2d)
filtered through Celite, and the filtrate was concentrated under
vacuum to afford an oily residue. The residue was purified by
column chromatography on silica gel. The fraction was collected and
concentrated to obtain 26.2 mg product 2a.
1
1) 2-Methylbenzo[d]oxazol-4-yl acetate (2a)
Yield: 42%. White solid; Mp: 71 – 74 °C; H NMR (600 MHz, CDCl
3
) δ
7
1
1
3
6
2
6
.68 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.06 (t, J = 8.0 Hz,
1
3
3
H), 2.67 (s, 3H). C NMR (150 MHz, CDCl ) δ 162.98, 148.46,
43.30, 132.32, 124.98, 109.22, 83.24, 13.59; IR (KBr): ν = 3357,
190, 3064, 2921, 2854, 1599, 1417, 1332, 1254, 1028, 904, 799,
-
1
97, 505 cm ; HRMS: Calculated for C
8 6
H INO: 259.9572, found:
59.9574.
1
Yield: 68%. White solid; Mp: 68 - 71 °C; H NMR (400 MHz, CDCl
3
) δ
) 2-Methylbenzo[d]oxazole-4-carbonitrile (2e)
7
2
1
1
1
1
2
.35 (d, J = 8.2 Hz, 1H), 7.29 – 7.23 (m, 1H), 7.04 (d, J = 8.0 Hz, 1H),
1
3
3
.62 (s, 3H), 2.40 (s, 3H). C NMR (100 MHz, CDCl ) δ 168.92,
64.23, 152.36, 141.08, 134.16, 125.67, 124.59, 108.16, 20.93,
4.54; IR (KBr): ν = 2925, 2855, 1769, 1620, 1493, 1438, 1373, 1253,
-1
193, 1044, 866, 803, 743, 582 cm ; HRMS: Calculated for C10
92.0660, found: 192.0653.
9 3
H NO :
1
Yield: 74%. White solid; Mp: 110 - 113 °C; H NMR (600 MHz, CDCl
3
)
δ 7.46 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.16 (t, J = 8.0 Hz,
) 2-Methylbenzo[d]oxazol-4-yl acetate (2a)
1
3
1
1
3
6
1
7
3
H), 2.66 (s, 3H). C NMR (150 MHz, CDCl ) δ 164.28, 153.03,
49.37, 134.74, 126.98, 126.38, 126.21, 120.22, 22.27; IR (KBr): ν =
172, 3040, 2914, 2019, 1684, 1619, 1462, 1259, 1026, 885, 780,
-
1
67, 595 cm ; HRMS: Calculated for C
59.0560.
9 6 2
H N O: 159.0558, found:
) Methyl 2-methylbenzo[d]oxazole-4-carboxylate (2f)
1
Yield: 68%. White solid; Mp: 68 - 71 °C; H NMR (400 MHz, CDCl ) δ
3
7
2
1
.35 (d, J = 8.2 Hz, 1H), 7.29 – 7.23 (m, 1H), 7.04 (d, J = 8.0 Hz, 1H),
1
3
.62 (s, 3H), 2.40 (s, 3H). C NMR (100 MHz, CDCl ) δ 168.92,
3
64.23, 152.36, 141.08, 134.16, 125.67, 124.59, 108.16, 20.93,
4
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1
Yield: 89%. White solid; Mp: 80 - 83 °C; H NMR (400 MHz, CDCl
3
) δ
7
1
1
1
1
1
8
.95 (d, J = 7.8 Hz, 1H), 7.64 (d, J = 8.1 Hz, 1H), 7.32 (t, J = 7.9 Hz,
1
3
3
H), 4.00 (s, 3H), 2.69 (s, 3H). C NMR (100 MHz, CDCl ) δ 165.89,
65.72, 151.49, 140.94, 126.60, 123.87, 121.52, 114.56, 52.48,
4.77; IR (KBr): ν = 3360, 2933, 2852, 1719, 1573, 1430, 1294, 1144,
1
-
1
Yield: 52%. White solid; Mp: 55 - 58°C; H NMR (600 MHz, CDCl ) δ
3
023, 926, 865, 807, 758 cm ; HRMS: Calculated for C10
92.0660, found: 192.0652.
9 3
H NO :
1
3
7
.07 (s, 1H), 6.84 (d, J = 10.6 Hz, 1H), 2.62 (s, 3H), 2.45 (s, 3H).
C
NMR (150 MHz, CDCl ) δ 163.42, 153.53, 151.01, 135.79, 127.73,
3
) 6-Chloro-2,4-dimethylbenzo[d]oxazole (2i)
1
1
11.56, 106.53, 21.68, 14.39; IR (KBr): ν = 3364, 2924, 2826, 1624,
-1
424, 1259, 1089, 1027, 805, 697, 503 cm ; HRMS: Calculated for
C H FNO: 166.0668, found: 166.0665.
9
8
1
3) 4-Chloro-2,6-dimethylbenzo[d]oxazole (2n)
1
Yield: 80%. White solid; Mp: 82 - 85 °C; H NMR (400 MHz, CDCl
3
) δ
1
3
7
.30 (s, 1H), 7.09 (s, 1H), 2.62 (s, 3H), 2.55 (s, 3H). C NMR (100
MHz, CDCl ) δ 163.55, 150.71, 139.41, 130.67, 129.64, 125.19,
08.19, 16.27, 14.44; IR (KBr): ν = 3426, 2926, 2858, 1732, 1617,
3
1
1
1
9
-1
1
459, 1254, 1160, 925, 823 cm ; HRMS: Calculated for C
82.0373, found: 182.0365.
9
H
8
ClNO: Yield: 77%. White solid; Mp: 72 - 75°C; H NMR (600 MHz, CDCl
3
) δ
13
7.09 (s, 1H), 7.05 (s, 1H), 2.56 (s, 3H), 2.36 (s, 3H). C NMR (150
MHz, CDCl ) δ 163.03, 150.73, 136.05, 134.71, 124.33, 122.14,
08.16, 20.47, 13.45; IR (KBr): ν = 3492, 2924, 2858, 1696, 1613,
) 6-Bromo-2, 4-dimethylbenzo[d]oxazole (2j)
3
1
1
-1
468, 1256, 1188, 1099, 1025, 923, 811, 698, 594, 467 cm ; HRMS:
ClNO: 182.0373, found: 182.0372.
4) 4-Bromo-2,6-dimethylbenzo[d]oxazole (2o)
9 8
Calculated for C H
1
1
Yield: 84%. White solid; Mp: 101 - 104 °C; H NMR (600 MHz, CDCl )
3
1
3
δ 7.44 (s, 1H), 7.23 (s, 1H), 2.61 (s, 3H), 2.54 (s, 3H). C NMR
150MHz, CDCl ) δ 163.48, 151.04, 139.92, 131.21, 127.96, 117.03,
(
3
111.10, 16.24, 14.46; IR (KBr): ν = 3359, 3177, 3101, 3038, 2921,
1
2
853, 1695, 1610, 1451, 1391, 1256, 1202, 1050, 921, 803, 684, 591
Yield: 76%. White solid; Mp: 96 - 99 °C; H NMR (400 MHz, CDCl ) δ
3
-1
13
cm ; HRMS: Calculated for C H BrNO: 225.9868, found: 225.9857.
9
8
7.29 (s, 1H), 7.20 (s, 1H), 2.63 (s, 3H), 2.43 (s, 3H). C NMR (100
10) Methyl 2,6-dimethylbenzo[d]oxazole-4-carboxylate (2k)
MHz, CDCl ) δ 163.90, 151.11, 138.71, 136.12, 128.23, 111.14,
3
1
1
2
1
09.72, 21.38, 14.49; IR (KBr): ν = 3430, 2926, 2858, 1748, 1611,
-1
458, 1249, 1117, 834 cm ; HRMS: Calculated for C H BrNO:
9
8
25.9868, found: 225.9850.
5) 2,4-Dimethylbenzo[d]oxazol-6-yl acetate (2p)
1
Yield: 81%. White solid; Mp: 101 - 104 °C; H NMR (400 MHz, CDCl
3
3
)
COOCH3
1
δ 7.78 (s, 1H), 7.45 (s, 1H), 4.00 (s, 3H), 2.67 (s, 3H), 2.48 (s, 3H).
NMR (100 MHz, CDCl ) δ 165.88, 165.24, 151.85, 138.78, 134.33,
27.55, 120.78, 114.85, 52.45, 21.41, 14.70; IR (KBr): ν = 3424, 2928,
C
N
3
1
1
O
H C
3
-
1
765, 1624, 1434, 1374, 1208, 1118, 1064, 1020, 903, 600 cm ;
: 206.0817, found: 206.0790.
1) Methyl 2,4-dimethylbenzo[d]oxazole-6-carboxylate (2l)
1
Yield: 93%. White solid; Mp: 119 - 122 °C; H NMR (400 MHz, CDCl
3
13
)
HRMS: Calculated for C11
H
11NO
3
δ 7.06 (s, 1H), 6.82 (s, 1H), 2.61 (s, 3H), 2.55 (s, 3H), 2.30 (s, 3H).
NMR (100 MHz, CDCl
C
1
3
) δ 169.66, 163.64, 150.38, 147.27, 138.48,
30.15, 118.53, 101.73, 21.03, 16.42, 14.45; IR (KBr): ν = 2932, 2580,
1
1
-
1
714, 1523, 1439, 1323, 1245, 1197, 1036, 859, 789, 594 cm ;
: 206.0817, found: 206.0790.
6) 2,4,6-Trimethylbenzo[d]oxazole (2q)
HRMS: Calculated for C11H11NO
3
1
1
CH3
3
Yield: 90%. White solid; Mp: 105 - 108 °C; H NMR (400 MHz, CDCl )
1
3
δ 7.95 (s, 1H), 7.82 (s, 1H), 3.92 (s, 3H), 2.65 (s, 3H), 2.59 (s, 3H).
NMR (100 MHz, CDCl ) δ 166.90, 165.78, 150.27, 144.55, 129.48,
26.34, 126.17, 109.32, 52.21, 16.37, 14.68; IR (KBr): ν = 3712, 3434,
C
N
O
3
1
2
H C
-1
3
934, 1712, 1625, 1449, 1050, 889, 796, 731, 659, 540 cm ; HRMS:
: 206.0817, found: 206.0790.
2) 4-Fluoro-2,6-dimethylbenzo[d]oxazole (2m)
1
3
Yield: 62%. White solid; Mp: 66- 69°C; H NMR (400 MHz, CDCl ) δ
Calculated for C11H11NO
3
1
3
7
.09 (s, 1H), 6.92 (s, 1H), 2.61 (s, 3H), 2.54 (s, 3H), 2.42 (s, 3H). C
1
3
NMR (100 MHz, CDCl ) δ 162.42, 150.95, 138.36, 134.29, 128.90,
1
2
25.94, 107.72, 21.59, 16.38, 14.50; IR (KBr): ν = 3721, 3362, 2923,
-1
855, 1644, 1458, 1261, 1093, 1029, 805, 695 cm ; HRMS:
Calculated for C10H11NO: 162.0919, found: 162.0915.
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DOI: 10.1039/C7OB02566A
ARTICLE
Journal Name
17) 4,6-Dichloro-2-methylbenzo[d]oxazole (2r)
712; (c) D. N. Rana, M. T. Chhabria, N. K. Shah and P. S.
Brahmkshatriya, Med. Chem. Res., 2014, 23, 2218; (d) D.
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2,
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1
Yield: 58%. White solid; Mp: 62- 65°C; H NMR (600 MHz, CDCl
3
) δ
) δ
1
3
7
.40 (s, 1H), 7.33 (s, 1H), 2.66 (s, 3H). C NMR (150 MHz, CDCl
3
1
65.26, 151.33, 138.20, 130.33, 124.83, 124.31, 109.73, 14.52; IR
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(a) C. L. Galatis, J. Am. Chem. Soc., 1948, 70, 1967; (b) J.
Chang, K. Zhao and S. Pan, Tetrahedron Lett., 2002, 43, 951;
(KBr): ν = 3360, 2924, 2856, 1624, 1424, 1259, 1089, 1027, 805, 697,
-
1
2
5
2
1
03 cm ; HRMS: Calculated for C
8 5 2
H Cl NO: 201.9826, found:
01.9815.
(
c) F. Z. Su, S. C. Mathew, L. Molmann, M. Antonietti, X. C.
Wang and S. Blechert, Angew. Chem. Int. Ed., 2011, 50, 657;
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(
Mourabit, Org. Lett., 2012, 14, 5948; (e) W. C. Li, C. C. Zeng,
L. M. Hu, H. Y. Tian and R. D. Little, Adv. Synth. Catal., 2013,
3
55, 2884; (f) L. J. Gu, C. Jin, J. M. Guo, L. Z. Zhang and W.
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1
Yield: 41%. White solid; Mp: 148 - 151 °C; H NMR (400 MHz, CDCl )
3
13
δ 7.63 (s, 1H), 7.59 (s, 1H), 2.65 (s, 3H). C NMR (100 MHz, CDCl ) δ
3
1
65.26, 151.33, 138.20, 130.33, 124.83, 124.31, 109.73, 14.52; IR
3
4
(
KBr): ν = 3717, 3424, 3087, 2926, 2858, 1725, 1608, 1448, 1388,
-
1
1
258, 1158, 1051, 939, 848, 745 cm ; HRMS: Calculated for
2
014, 50, 6145; (c) K. R. Babu, N. B. Zhu and H. L. Bao, Org.
C H Br NO: 289.8816, found: 289.8798.
8
5
2
Lett., 2017, 19, 46; (d) G. Altenhoff and F. Glorius, Adv. Synth.
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4
. The control reaction using N-phenylacetamide as substrate
Pd(OAc) (22.5 mg, 0.10 mmol), N-phenylacetamide (135.0 mg, 1.0
2
mmol), glacial acetic acid (4.0 mL), N,N-dimethylformamide (0.5 mL),
potassium peroxodisulfate (500.0 mg, 1.5 mmol), and TfOH (150.0
mg, 1.0 mmol) were placed into a 15-mL sealed tube, and heated in
o
an oil bath at 100 C for 24 h. Reaction mixture (0.2 mL) was taken
out from tube at 3 hours interval. After work up, the oily residue
was detected by HPLC on C18 reversed phase column, methanol:
water = 50 : 50, flow rate = 1.0 mL/min. The yields were determined
with 1,3,5-trimethoxybenzene as an internal standard.
K. V. N. Esguerra and J. P. Lumb, ACS Catal., 2017,
(
7, 3477;
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(a) Y. Yuan, D. T. Chen and X. W. Wang, Adv. Synth. Catal.,
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2
2
011, 353, 3373; (b) H. Liu, H. Xu and Y. Yuan, Tetrahedron,
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013, 45, 1247.
Conflicts of interest
6
7
G. W. Wang, T. T. Yuan and X. L. Wu, J. Org. Chem., 2008, 73
717.
(a) R. Das and M. Kapur, J. Org. Chem., 2017, 82, 1114; (b) J.
Jiang, W. M. Zhang, J. J. Dai, J. Xu and H. J. Xu, J. Org. Chem.,
,
4
There are no conflicts to declare.
2
017, 82, 3622; (c) O. Tischler, Z. Bokányi and Z. Novák,
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Acknowledgements
6
This work was supported by Jiangsu Provincial Nature Science
Foundation (SBK2016021885), Top-notch Academic Programs
Project of Jiangsu Higher Education Institutions, and the
Priority Academic Program Development of Jiangsu Higher
Education Institutions.
(
Notes and references
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| J. Name., 2012, 00, 1-3
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