Base-promoted formal arylation of benzo[d]oxazoles with acyl chloride

Article abstract of DOI:10.1021/jo402106q

A base-promoted formal arylation of benzo[d]oxazoles with acyl chloride was achieved in moderate to good yields. This reaction was triggered by the N-acylation of oxazole to form an iminium intermediate. Then, the addition of H₂O to the iminium formed the hemiacetal intermediate. After the sequential ring-opening, extrusion of CO, the ring closure, the dehydration delivered the formal arylation product. In comparison with the transition-metal-catalyzed methodology, it represents an alternative arylation method leading to 2-arylbenzooxazole.

Full text of DOI:10.1021/jo402106q

Article
pubs.acs.org/joc
Base-Promoted Formal Arylation of Benzo[d]oxazoles with Acyl
Chloride
Lei Wang,† Xinyi Ren,‡ Jintao Yu,† Yan Jiang,† and Jiang Cheng*,†,‡
†School of Petrochemical Engineering, Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Jiangsu Province
Key Laboratory of Fine Petrochemical Engineering, Changzhou University, Changzhou 213164, P. R. China
‡College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. China
S
* Supporting Information
ABSTRACT: A base-promoted formal arylation of benzo[d]-
oxazoles with acyl chloride was achieved in moderate to good
yields. This reaction was triggered by the N-acylation of
oxazole to form an iminium intermediate. Then, the addition of H2O to the iminium formed the hemiacetal intermediate. After
the sequential ring-opening, extrusion of CO, the ring closure, the dehydration delivered the formal arylation product. In
comparison with the transition-metal-catalyzed methodology, it represents an alternative arylation method leading to 2-
arylbenzooxazole.
reported by Li.12 However, a transition metal was required
for all of the aforementioned transformations.
INTRODUCTION
The frameworks of 2-arylbenzooxazole are widely found in
■
pharmaceuticals, organic dyes, and natural products.1 The
Recently, the carboxylic acid derivatives were widely used as
the arylating reagent via the transition-metal-catalyzed decar-
direct arylation of benzooxazole C−H bond was the most
boxylation13 or decarbonylation.14 We envisioned that arylation
straightforward method to construct this structure because
prefunctionalization is not required.2 As such, the use of
PhSO2X,3 aryl boron,4 aryl silicon,5 aryl tin,6 phenol
derivatives,7 and aryl halide8 as arylation reagents in such
transformations was well developed (Scheme 1, eq 1).
of the benzooxazole C−H bond could be achieved by the
transition-metal-catalyzed decarbonylative coupling of acyl
chloride (Scheme 1, eq 2).15 With this in mind, we found an
unexpected transition-metal-free base-promoted formal aryla-
tion of benzooxazole stemmed from its inherent property by
acyl chloride proceeding through a ring-opening and closure
pathway (Scheme 1, eq 3). Although 2-arylbenzooxazole could
be facile prepared from the annulation of 2-hydroxyphenyl-
amine and benzoic acid,16 from the functional group trans-
formation point of view, this formal arylation procedure
represents an alternative arylation method leading to 2-aryl
benzooxazole. Herein, we report our study on it.
Scheme 1. Arylation of Benzooxazole
RESULTS AND DISCUSSION
■
Initially, in light of our recent work on the copper(II)-catalyzed
ortho-functionalization of 2-arylpyridines with acyl chlorides,17
we envisioned developing the copper-catalyzed decarbonylation
of acyl chloride by in situ formation of anhydride in the
presence of base and H2O. Indeed, heating the combination of
benzooxazole, benzoyl chloride (2 equiv), CuCl2 (0.2 equiv),
and K2CO3 (1 equiv) in H2O (0.4 mL) at 140 °C afforded the
arylation product in 23% yield. To our surprise, the arylation
product was isolated in a slightly higher yield of 31% in the
absence of CuCl2 (table 1, entry 1). Further studies revealed
the employment of cosolvent also delivered the yield in the
absence of any transition metal. In PhCl/H2O (1/1), the
arylation product was isolated in 31% yield in the presence of 1
equiv of K2CO3 (Table 1, entry 3). To our delight, the yield
Meanwhile, other arylation regents were also well developed.
For example, in 2012, we described a palladium-catalyzed direct
arylation of benzooxazole with ArI(OAc)2.9 Su reported the
palladium-catalyzed direct arylation of benzooxazole by simple
unactivated arene.10 Wang demonstrated the palladium-
catalyzed deamidative arylation of azoles with arylamides.11
The iron-catalyzed arylation of oxazole by aldehyde was
Received: September 23, 2013
© XXXX American Chemical Society
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ClC6H4COCl and benzooxazole, 2-phenylbenzooxazole was
isolated in 81% yield (Scheme 2, eq 3). Under the standard
procedure, the extrusion of CO was detected by phosphomo-
lybdic acid strip and none of CO was detected in the reaction of
eq 4 in Scheme 2 (for details, see the Supporting Information).
In the presence of 0.2 mL of Hg(0), 3a was isolated in a
comparable 70% yield under the standard procedure, ruling out
the possibility of trace of transition metal as the true catalyst.
Based on these experimental results, we believed the reaction
proceeded through a sequential ring-opening and closure
pathway, as illustrated in Scheme 3. First, in the presence of
Table 1. Selected Results for Screening the Optimized
Reaction Conditions
a
entry
base
solvent
yield(%)
1
2
3
4
5
6
7
8
9
10
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
Na2CO3
NaHCO3
t-BuOK
NaOAc
KOH
H2O
31
24
31
CH3CN/H2O = 1:1 (0.6 mL)
PhCl/H2O = 1:1 (0.6 mL)
PhCl/H2O = 3:1 (0.4 mL)
PhCl/H2O = 3:1 (0.4 mL)
PhCl/H2O = 3:1 (0.4 mL)
PhCl/H2O = 3:1 (0.4 mL)
PhCl/H2O = 3:1 (0.4 mL)
PhCl/H2O = 3:1 (0.4 mL)
PhCl/H2O = 3:1 (0.4 mL)
b
82 (41)
71
36
61
43
49
50
Scheme 3. Proposed Mechanism
a
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), K2CO3 (1.0
b
equiv), air, 140 °C, 12 h, sealed tube. N2.
dramatically increased to 82% by adjusting the ratio of PhCl
and H2O to 3:1 (table 1, entry 4). A 41% yield was obtained
under N2. Under this cosolvent, replacing K2CO3 with other
bases, such as K3PO4, Na2CO3, NaHCO3, t-BuOK, NaOAc, and
KOH, resulted in low efficiency (Table 1, entries 5−10).
More experiments were conducted to gain some insight into
this unexpected reaction. Replacing acyl chloride with benzoic
acid, the arylation product was isolated in less than 5% yield
either in the presence or the absence of K2CO3 (1 equiv) and
KHCO3 (1 equiv) (Scheme 2, eq 1). Benzoic potassium also
base, the N-acylation of benzooxazole takes place to form the
iminium species 5.18 The poor reactivity of benzoic acid in this
procedure is at least partly due to its poor ability in this
acylating step. Then, the hemiacetal intermediate 6 is formed
by the nucleophilic attack of H2O to the iminium 5. Second,
the equilibrium reaction between aldehyde and hemiacetal
facilitates the ring-opening of intermediate 6 to form
intermediate 7. Then, the formed intermediate 7 produces
intermediate 8 by the loss of CO.19 Third, the cyclization of
intermediate 8 forms the hemiacetal intermediate 9. Finally, the
dehydration of intermediate 9 delivers the formal arylation
product.
Scheme 2. Mechanism Study
Next, we examined the substrate scope of acyl chlorides in
this arylation reaction. As shown in Figure 1, acyl chlorides
substituted with a series of functional groups at the phenyl ring,
such as chloro, fluoro, as well as trifluoromethyl, afforded
satisfactory yields (3d−i, Figure 1). Either electron-rich or
electron-poor substrates readily reacted with benzo[d]oxazole
in good to excellent yields. For some substrates with electron-
withdrawing substituents, prolonged reaction time was
required. In particular, the electron-poor m-trifluoromethylben-
zoyl delivered the arylation product in 91% yield (3h, Figure 1).
The steric hindrance had little effect on the reaction. For
example, 3f was isolated in 80% yield. Notably, cyclo-
hexanecarbonyl chloride also took part in this reaction with
moderate yield (3j, Figure 1).
Next, we conducted the reaction of benzo[d]oxazole and 4-
trifluoromethylbenzoyl chloride on a 6 mmol scale with
elongated time (20 h). To our delight, 3i was isolated in a
comparable 84% (1.319 g) yield.
Encouraged by these promising results, various benzo[d]-
oxazole derivatives were tested. To our delight, different
functional groups including 5-methyl, 5-chloro, 6-methyl, and
5-tert-butyl were well tolerated (4a−g, Figure 2). Satisfyingly,
failed to deliver the arylation product. To our surprise, in the
presence and absence of K2CO3, benzoic anhydride only
delivered the arylation product in <5% and 20% yields,
respectively (Scheme 2, eq 2). These results ruled out the
possibility of benzoic acid and anhydride as the intermediate in
this transformation. Further study revealed compound 8 was
detected during this reaction. When 0.2 equiv of compound 8
was subjected to the standard reaction system of 2-
B
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in the formal arylation under the standard procedure in low
yield (4i, Figure 2).
CONCLUSION
■
In conclusion, we have developed a base-promoted protocol of
formal benzooxazole 2-arylation using aryl chloride as the
coupling partner. N-acylated product of oxazole served as the
intermediate in this transformation. Then, the sequential
addition of H2O, ring-opening, extrusion of CO, ring closure,
and dehydration delivered the formal arylation product. It
represents an alternative arylation method leading to 2-aryl
benzooxazole.
EXPERIMENTAL SECTION
■
General Information. Chemicals were either purchased or
purified by standard techniques. 1H NMR and 13C NMR spectra
were measured on a 500 or 300 MHz spectrometer (1H 500 or 300
MHz, 13C 125 or 75 MHz) using CDCl3 as the solvent at room
temperature. Chemical shifts (in ppm) were referenced to
tetramethylsilane (δ = 0 ppm) or 7.26 ppm in CDCl3 as an internal
standard. 13C NMR spectra were obtained by using the same NMR
spectrometers and were calibrated with CDCl3 (δ = 77.00 ppm).
Chemical shifts are given in δ relative to TMS, and the coupling
constants J are given in Hz. Column chromatography was performed
using EM silica gel 60 (300−400 mesh).
Figure 1. Arylation of benzo[d]oxazole with acyl chlorides. (a)
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), K2CO3 (1.0 equiv),
solvent (0.4 mL, PhCl/H2O = 3/1), air, 140 °C, 12 h, sealed tube. (b)
24 h.
General Procedure. Under air atmosphere, a sealed reaction tube
was charged with benzo[d]oxazole (0.2 mmol), acyl chloride (0.4
mmol), K2CO3 (0.2 mmol), and PhCl/H2O = 3/1 (0.4 mL). The
mixture was kept stirring under air at 140 °C for 12 h. After
completion of the reaction (monitored by TLC), the mixture was
concentrated in vacuum, and the residue was purified by flash column
chromatography on silica gel with petroleum ether−ethyl acetate as
eluent to give the desired product.
2-Phenylbenzo[d]oxazole (3a).3d Flash column chromatography
on silica gel (ethyl acetate/petroleum ether, 1:20) gave the product
(31.9 mg, 82% yield) as a white solid: 1H NMR (CDCl3, 500 MHz) δ
8.28−8.26 (m, 2H), 7.79−7.78 (m, 1H), 7.60−7.58 (m, 1H), 7.54−
7.53 (m, 3H), 7.38−7.35 (m, 2H); 13C NMR (CDCl3, 125 MHz) δ
163.0, 150.8, 142.1, 131.5, 128.9, 127.6, 127.2, 125.1, 124.6, 120.0,
110.6.
2-(p-Tolyl)benzo[d]oxazole (3b).3d Flash column chromatog-
raphy on silica gel (ethyl acetate/petroleum ether, 1:20) gave the
product (34.6 mg, 83% yield) as a white solid: 1H NMR (CDCl3, 500
MHz) δ 8.15 (d, J = 8.2 Hz, 2H), 7.77−7.75 (m, 1H), 7.57−7.55 (m,
1H), 7.34−7.32 (m, 4H), 2.43 (s, 3H); 13C NMR (CDCl3, 125 MHz)
δ 163.3, 150.7, 142.2, 142.0, 129.6, 127.6, 124.8, 124.5, 124.4, 119.8,
110.5, 21.6.
2-(m-Tolyl)benzo[d]oxazole (3c).20 Flash column chromatog-
raphy on silica gel (ethyl acetate/petroleum ether, 1:20) gave the
product (29.1 mg, 70% yield) as a white solid: 1H NMR (CDCl3, 300
MHz) δ 8.10 (s, 1H), 8.06 (d, J = 7.6 Hz, 1H), 7.79−7.76 (m, 1H),
7.59−7.57 (m, 1H), 7.44−7.39 (m, 1H), 7.37−7.33 (m, 3H), 2.46 (s,
3H); 13C NMR (CDCl3, 125 MHz) δ 163.2, 150.7, 142.1, 138.7,
132.3, 128.8, 128.2, 127.0, 125.0, 124.7, 124.5, 119.9, 110.5, 21.3.
2-(4-Chlorophenyl)benzo[d]oxazole (3d).21 Flash column
chromatography on silica gel (ethyl acetate/ petroleum ether, 1:20)
1
gave the product (37.8 mg, 82% yield) as a white solid: H NMR
Figure 2. Arylation of benzo[d]oxazole derivatives with acyl chlorides.
(a) Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), K2CO3 (1.0
equiv), solvent (0.4 mL, PhCl/H2O = 3/1), air, 140 °C, 12 h, sealed
tube. (b) 24 h.
(CDCl3, 300 MHz) δ 8.19 (d, J = 8.7 Hz, 2H), 7.78−7.75 (m, 1H),
7.58−7.56 (m, 1H), 7.50 (d, J = 8.7 Hz, 2H), 7.38−7.35 (m, 2H); 13C
NMR (CDCl3, 125 MHz) δ 162.0, 150.7, 142.0, 137.7, 129.2, 128.8,
125.6, 125.3, 124.7, 120.1, 110.6.
2-(4-Fluorophenyl)benzo[d]oxazole (3e).3d Flash column
chromatography on silica gel (ethyl acetate/petroleum ether, 1:20)
gave the product (35 mg, 82% yield) as a white solid: 1H NMR
(CDCl3, 300 MHz) δ 8.27−8.23 (m, 2H), 7.79−7.74 (m, 1H), 7.58−
7.54 (m, 1H), 7.38−7.32 (m, 2H), 7.24−7.18 (m, 2H); 13C NMR
(CDCl3, 75 MHz) δ 164.8 (d, JC−F = 251.1 Hz), 162.1, 150.8, 142.0,
the electron-withdrawing substituents such as ethyloxycarbonyl
also tolerated well to afford the arylation products in moderate
yield (4h, Figure 2). Significantly, benzothiazole also took part
C
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129.8 (d, JC−F = 8.9 Hz), 125.1, 124.6, 123.5 (d, JC−F = 3.1 Hz,) 120.0,
116.1 (d, JC−F = 22.0 Hz,) 110.5.
1H), 7.47 (d, J = 8.7 Hz, 2H), 7.35 (s, 1H), 7.16 (d, J = 8.15 Hz, 1H),
2.50 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 161.5, 151.0, 139.8,
137.4, 135.8, 129.2, 128.6, 125.9, 125.8, 119.4, 110.7, 21.8.
2-(2-Chlorophenyl)benzo[d]oxazole (3f).21 Flash column chro-
matography on silica gel (ethyl acetate/petroleum ether, 1:20) gave
6-Methyl-2-(3-(trifluoromethyl)phenyl)benzo[d]oxazole
(4e). Flash column chromatography on silica gel (ethyl acetate/
petroleum ether, 1:20) gave the product (44.9 mg, 81% yield) as a
1
the product (36.8 mg, 80% yield) as a white solid: H NMR (CDCl3,
300 MHz) δ 8.16 (dd, J1 = 7.5, J2 = 2.0 Hz, 1H), 7.86−7.85 (m, 1H),
7.63−7.61 (m, 1H), 7.58−7.56 (m, 1H), 7.47−7.37 (m, 4H); 13C
NMR (CDCl3, 125 MHz) δ 160.9, 150.6, 141.6, 133.5, 131.9, 131.8,
131.4, 126.9, 126.3, 125.5, 124.6, 120.5, 110.7.
1
white solid: mp 84−85 °C. H NMR (CDCl3, 500 MHz) δ 8.50 (s,
1H), 8.40 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.66−7.62 (m,
2H), 7.39 (s, 1H), 7.19 (d, J = 8.0 Hz, 1H), 2.51 (s, 3H); 13C NMR
(CDCl3, 125 MHz) δ 161.0, 151.1, 139.7, 136.2, 131.6 (q, JC−F = 32.5
Hz), 130.4, 129.5, 128.2, 127.6(q, JC−F = 3.6 Hz), 126.2, 124.4 (q, JC−F
= 3.6 Hz), 123.7 (q, JC−F = 270.8 Hz), 119.6, 110.8, 21.8; IR (prism,
cm−1): 1708, 1363, 1223, 1123, 808; MS(EI) 277 (M+); HRMS (ESI-
TOF, [M + H]+) calcd for C15H11F3NO (M + H)+ 278.0787, found
278.0787.
2-(2,4-Dichlorophenyl)benzo[d]oxazole (3g).21 Flash column
chromatography on silica gel (ethyl acetate/petroleum ether, 1:20)
1
gave the product (31.7 mg, 60% yield) as a white solid: H NMR
(CDCl3, 500 MHz) δ 8.12 (d, J = 8.5 Hz, 1H), 7.84 (d, J = 6.7
Hz,1H), 7.62−7.59 (m, 2H), 7.42−7.39 (m, 3H); 13C NMR (CDCl3,
125 MHz) δ 160.1, 150.5, 141.6, 137.5, 134.3, 132.5, 131.3, 127.4,
125.8, 124.8, 124.7, 120.6, 110.8.
5-tert-Butyl-2-(3-(trifluoromethyl)phenyl)benzo[d]oxazole
(4f). Flash column chromatography on silica gel (ethyl acetate/
petroleum ether, 1:20) gave the product (54.2 mg, 85% yield) as a
white solid: mp 113−114 °C; 1H NMR (CDCl3, 500 MHz) δ 8.52 (s,
1H), 8.42 (d, J = 7.8 Hz, 1H), 7.82 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H),
7.64 (t, J = 7.8 Hz, 1H), 7.51 (d, J = 8.6 Hz, 1H), 7.45 (m, J = 8.6 Hz,
1H), 1.41 (s, 9H); 13C NMR (CDCl3, 125 MHz) δ 161.6, 148.8,
148.5, 141.8, 131.6 (q, JC−F = 32.6 Hz), 130.5, 129.5, 128.2, 127.7 (q,
JC−F = 3.5 Hz) 124.4 (q, JC−F = 3.6 Hz), 124.1 (q, JC−F = 270.6 Hz),
116.8, 109.9, 35.0, 31.7; IR (prism, cm−1): 1708, 1363, 1223, 1131,
810; MS(EI) 319 (M+); HRMS (ESI-TOF, [M + H]+) calcd for
C18H17F3NO (M + H)+ 320.1257, found 320.1258.
5-Chloro-2-(3-(trifluoromethyl)phenyl)benzo[d]oxazole
(4g).3d Flash column chromatography on silica gel (ethyl acetate/
petroleum ether, 1:20) gave the product (42.2 mg, 71% yield) as a
white solid: 1H NMR (CDCl3, 300 MHz) δ 8.48 (s, 1H), 8.39 (d, J =
7.8 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.75 (s, 1H), 7.65 (t, J = 8.0 Hz,
1H), 7.52−7.51 (m, 1H), 7.36−7.34 (m, 1H); 13C NMR (CDCl3, 125
MHz) δ 162.8, 149.3, 143.0, 131.7 (q, JC−F = 33.1 Hz), 130.7, 130.4,
129.6, 128.3 (q, JC−F = 3.8 Hz), 127.6, 126.0, 124.6 (q, JC−F = 3.9 Hz),
123.6 (q, JC−F = 271.0 Hz), 120.3, 111.5.
2-(3-(Trifluoromethyl)phenyl)benzo[d]oxazole (3h).20 Flash
column chromatography on silica gel (ethyl acetate/petroleum ether,
1:10) gave the product (48.0 mg, 91% yield) as a white solid: 1H NMR
(CDCl3, 500 MHz) δ 8.53 (s, 1H), 8.43 (d, J = 7.8 Hz, 1H), 7.80−
7.77 (m, 2H), 7.66 (t, J = 7.8 Hz, 1H), 7.62−7.60 (m, 1H), 7.41−7.37
(m, 2H); 13C NMR (CDCl3, 125 MHz) δ 161.5, 150.8, 141.9, 131.6
(q, JC−F = 32.7 Hz,), 130.6, 129.5, 128.1, 127.9 (q, JC−F = 3.5 Hz),
125.7, 124.9, 124.5 (q, JC−F = 3.9 Hz), 123.7 (q, JC−F = 271.0 Hz),
120.3, 110.8.
2-(4-(Trifluoromethyl)phenyl)benzo[d]oxazole (3i).3c Flash
column chromatography on silica gel (ethyl acetate/petroleum ether,
1:10) gave the product (48.0 mg, 91% yield) as a white solid: 1H NMR
(CDCl3, 300 MHz) δ 8.38 (d, J = 8.1 Hz, 2H), 7.82−7.78 (m, 3H),
7.64−7.60 (m, 1H), 7.44−7.39 (m, 2H);13C NMR (CDCl3, 75 MHz)
δ 161.4, 150.8, 141.8, 132.9 (q, JC−F = 32.8 Hz), 130.3, 127.7, 125.8 (q,
JC−F = 3.75 Hz), 124.8, 123.7 (q, JC−F = 270.8 Hz), 120.3, 110.7.
2-Cyclohexylbenzo[d]oxazole (3j).23 Flash column chromatog-
raphy on silica gel (ethyl acetate/petroleum ether, 1:20) gave the
product (24.1 mg, 60% yield) as a colorless oil: 1H NMR (CDCl3, 300
MHz) δ 7.69−7.66 (m, 1H), 7.48−7.45 (m, 1H), 7.27 (dd, J1 = 6.0
Hz, J2 = 3.2 Hz, 2H), 3.00−2.89 (m, 1H), 2.18−2.13 (m, 2H), 1.89−
1.84 (m, 2H), 1.76−1.64 (m, 3H), 1.49−1.25 (m, 3H); 13C NMR
(CDCl3, 75 MHz) δ 170.3, 150.5, 141.2, 124.3, 123.9, 119.5, 110.2,
37.9, 30.4, 25.7, 25.6.
Ethyl 2-(3-(Trifluoromethyl)phenyl)benzo[d]oxazole-5-car-
boxylate (4h). Flash column chromatography on silica gel (ethyl
acetate/petroleum ether, 1:10) gave the product (41.6 mg, 62% yield)
as a white solid: mp 109−110 °C; 1H NMR (CDCl3, 500 MHz) δ 8.51
(s, 1H), 8.48 (s, 1H), 8.42 (d, J = 7.9 Hz, 1H), 8.14 (dd, J1 = 8.6 Hz, J2
= 1.6 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.8 Hz, 1H), 7.62
(d, J = 8.6 Hz, 1H), 4.42 (q, J1 = 7.2 Hz, 2H), 1.43 (t, J = 7.2 Hz, 3H);
13C NMR (CDCl3, 125 MHz) δ 166.0, 162.7, 153.6, 141.9, 131.7 (q,
5-Methyl-2-phenylbenzo[d]oxazole (4a).3c Flash column chro-
matography on silica gel (ethyl acetate/petroleum ether, 1:20) gave
1
the product (35.7 mg, 85% yield) as a white solid: H NMR (CDCl3,
500 MHz) δ 8.26−8.24 (m, 2H), 7.56 (s, 1H), 7.52−7.51 (m, 3H),
7.45 (d, J = 8.3 Hz, 1H), 7.16 (d, J = 8.2 Hz, 1H), 2.49 (s, 3H); 13C
NMR (CDCl3, 125 MHz) δ 163.1, 149.0, 142.3, 134.3, 131.3, 128.8,
127.5, 127.3, 126.2, 119.9, 109.9, 21.5.
JC−F = 32.0 Hz), 130.8, 129.6, 128.3 (q, JC−F = 3.6 Hz), 127.8, 127.5,
124.6 (q, JC−F = 4.4 Hz), 123.4 (q, JC−F = 271.0 Hz), 122.2, 110.5,
61.3, 14.3; IR (prism, cm−1) 1709, 1365, 1223, 1119, 812; MS(EI) 335
(M+); HRMS (ESI-TOF, [M + H]+) calcd for C17H13F3NO3 (M +
H)+ 336.0842, found 336.0857.
5-Methyl-2-(3-(trifluoromethyl)phenyl)benzo[d]oxazole
(4b). Flash column chromatography on silica gel (ethyl acetate/
petroleum ether, 1:20) gave the product (41.2 mg, 74% yield) as a
white solid: mp 116−117 °C; 1H NMR (CDCl3, 500 MHz) δ 8.50 (s,
1H), 8.40 (d, J = 7.8 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H), 7.64 (t, J = 7.9
Hz, 1H), 7.56 (s, 1H), 7.46 (d, J = 8.3 Hz, 1H), 7.19 (d, J = 8.3 Hz,
1H), 2.49 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ 161.5, 149.1,
142.1, 134.8, 131.6 (q, JC−F = 32.6 Hz), 130.5, 129.4, 128.2, 127.7 (q,
JC−F = 3.5 Hz), 126.8, 124.4 (q, JC−F = 3.8 Hz), 123.7 (q, JC−F = 270.9
Hz), 120.1, 110.1, 21.5; IR (prism, cm−1): 1713, 1345, 1223, 1114,
804; MS(EI) 277 (M+); HRMS (ESI-TOF, [M + H]+) calcd for
C15H11F3NO 278.0787, found 278.0788.
2-(4-Chlorophenyl)benzo[d]thiazole (4i).24 Flash column
chromatography on silica gel (ethyl acetate/petroleum ether, 1:20)
1
gave the product (7.5 mg, 15% yield) as a white solid: H NMR
(CDCl3, 300 MHz) δ 8.07 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 8.6 Hz,
2H), 7.90 (d, J = 7.9 Hz, 1H), 7.53−7.45 (m, 3H), 7.40 (t, J = 7.1 Hz,
1H); 13C NMR (CDCl3, 75 MHz) δ 166.6, 154.1, 137.0, 135.0, 132.1,
129.3, 128.7, 126.5, 125.4. 123.3, 121.6.
5-Chloro-2-p-tolylbenzo[d]oxazole (4j).3c Flash column chro-
matography on silica gel (ethyl acetate/petroleum ether, 1:20) gave
1
the product (22.7 mg, 47% yield) as a white solid: H NMR (CDCl3,
2-(4-Chlorophenyl)-5-methylbenzo[d]oxazole (4c).21 Flash
column chromatography on silica gel (ethyl acetate/petroleum ether,
1:20) gave the product (37.0 mg, 76% yield) as a white solid: 1H NMR
(CDCl3, 500 MHz) δ 8.16 (d, J = 8.6 Hz, 2H), 7.54 (s, 1H), 7.48 (d, J
= 8.5 Hz, 2H), 7.43 (d, J = 8.3 Hz, 1H), 7.16 (d, J = 8.3 Hz, 1H), 2.48
(s, 3H); 13C NMR (CDCl3, 125 MHz) δ 162.1, 148.9, 142.1, 137.5,
134.5, 129.1, 128.7, 126.4, 125.8, 119.9, 109.9, 21.5.
300 MHz) δ 8.09 (d, J = 8.2 Hz, 2H), 7.71 (d, J = 2.0 Hz, 1H), 7.45
(d, J = 8.6 Hz, 1H), 7.32−7.27 (m, 3H), 2.43(s, 3H); 13C NMR
(CDCl3, 75 MHz) δ 164.6, 149.2, 143.3, 142.5, 129.9, 129.6, 127.7,
125.0, 123.9, 119.7, 110.1, 21.6.
Procedure for the Synthesis of 3i on Gram Scale. Under air
atmosphere, a flask was charged with benzo[d]oxazole (0.715 g, 6
mmol), 4-trifluoromethylbenzoyl chloride (2.503 g, 12 mmol), K2CO3
(0.829 g, 6 mmol), and PhCl/H2O = 3/1 (12 mL). The mixture was
kept stirring under air at 140 °C for 20 h. After completion of the
reaction (monitored by TLC), the mixture was concentrated in
vacuum and the residue was purified by flash column chromatography
2-(4-Chlorophenyl)-6-methylbenzo[d]oxazole (4d).22 Flash
column chromatography on silica gel (ethyl acetate/petroleum ether,
1:20) gave the product (29.5 mg, 61% yield) as a white solid: 1H NMR
(CDCl3, 500 MHz) δ 8.14 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 8.1 Hz,
D
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Article
on silica gel with petroleum ether/ethyl acetate as eluent to give 3i
(1.319 g, 84%).
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra of compounds 3aa−aj and 3ba−ia.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jiangcheng@cczu.edu.cn.
■
Notes
The authors declare no competing financial interest.
(9) Yu, P.; Zhang, G.; Chen, F.; Cheng, J. Tetrahedron Lett. 2012, 53,
4588.
ACKNOWLEDGMENTS
(10) Wu, G.; Zhou, J.; Zhang, M.; Hu, P.; Su, W. Chem. Commun.
2012, 48, 8964.
(11) Li, C.; Li, P.; Yang, J.; Wang, L. Chem. Commun. 2012, 48, 4214.
(12) Liu, S.; Chen, R.; Guo, X.; Yang, H.; Deng, G.; Li, C.-J. Green
Chem. 2012, 14, 1577.
(13) (a) Cornella, J.; Larrosa, I. Synthesis 2012, 44, 653. (b) Dzik, W.
I.; Lange, P. P.; Gooßen, L. J. Chem. Sci. 2012, 3, 2671. (c) Shang, R.;
Liu, L. Sci. China Chem. 2011, 54, 1670. (d) Rodríguez, N.; Gooßen, L.
J. Chem. Soc. Rev. 2011, 40, 5030. (e) Gooßen, L. J.; Rodríguez, N.;
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Gooßen, K.; Rodríguez, N.; Blanchot, M.; Linder, C.; Zimmermann, B.
Pure Appl. Chem. 2008, 80, 1725. (g) Goossen, L. J.; Zimmermann, B.;
Knauber, T. Angew. Chem., Int. Ed. 2008, 47, 7103. (h) Goossen, L. J.;
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(i) Wang, C.; Rakshit, S.; Glorius, F. J. Am. Chem. Soc. 2010, 132,
14006.
■
We thank the National Natural Science Foundation of China
(nos. 21272028 and 21202013), “Innovation & Entrepreneur-
ship Talents” Introduction Plan of Jiangsu Province, Jiangsu
Key Laboratory of Advanced Catalytic Materials & Technology,
Jiangsu Province Key Laboratory of Fine Petrochemical
Engineering, and the Priority Academic Program Development
of Jiangsu Higher Education Institutions for financial support.
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