Copper-catalyzed synthesis of 2-arylbenzoxazoles from o-aminophenol derivatives with arylmethyl chlorides

Article abstract of DOI:10.1016/j.tet.2014.11.040

A facile and efficient synthesis of 2-arylbenzoxazoles via copper-catalyzed tandem condensation/oxidative reaction of o-aminophenol derivatives with arylmethyl chlorides was developed. Note that this reaction utilized arylmethyl chlorides as a new type of simple and cheap acyl sources and KNO₃ as a readily available and low-cost benign oxidant.

Full text of DOI:10.1016/j.tet.2014.11.040

Tetrahedron xxx (2014) 1e7
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper-catalyzed synthesis of 2-arylbenzoxazoles from
o-aminophenol derivatives with arylmethyl chlorides
*
*
Guodong Zhang, Peng Wang, Fan Yang , Yangjie Wu
The College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic Chemistry,
Key Laboratory of Applied Chemistry of Henan Universities, Zhengzhou University, 75 Daxue North Road, Zhengzhou 450052, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and efficient synthesis of 2-arylbenzoxazoles via copper-catalyzed tandem condensation/oxi-
dative reaction of o-aminophenol derivatives with arylmethyl chlorides was developed. Note that this
reaction utilized arylmethyl chlorides as a new type of simple and cheap acyl sources and KNO3 as
a readily available and low-cost benign oxidant.
Received 9 October 2014
Received in revised form 6 November 2014
Accepted 14 November 2014
Available online xxx
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Copper-catalyzed
2-Arylbenzoxazoles
o-Aminophenol
Arylmethyl chlorides
Condensation/oxidative
1. Introduction
Benzoxazole backbone is a ubiquitous structural unit in bi-
ologically active natural products, functional materials, alkaloids,
and particularly pharmaceuticals compounds due to its high bi-
ological activities, such as antitumor, antimicrobial, and antiviral
properties.1 The most primitive synthetic route is condensation of
o-aminophenol with carboxylic acids, which suffered from using
a strong acid as the raw material and the hash reaction conditions.2
Therefore, many efforts have been devoted to the development
of economical and environment-friendly routes to benzoxazole
derivatives.3
In recent years, two transition metal-promoted synthetic pro-
cesses have emerged as popular protocols for the construction
of the benzoxazole ring: one is the transition metal-catalyzed
intramolecular cyclization of ortho-haloanilides or their analogs
derivatives, and great progress has been achieved in the groups
of Glorius and others (Scheme 1a);4 the other is transition metal-
catalyzed intermolecular condensation/oxidative reaction of
o-aminophenol with an acyl source such as aromatic aldehyde,5
benzylic alcohol,6 benzylic amine7 and 1,3- diketones8 in the
presence of an oxidant (Scheme 1b). Recently, Wang group re-
ported an elegant procedure to aryl-substituted benzoxazoles from
Scheme 1. Synthetic strategies for the construction of benzoxazole skeleton.
o-aminophenol with toluene derivatives as the acyl source and
solvent under argon atmosphere,9 albeit this catalytic system may
not be suitable for the toluene derivatives with a melting point. On
the other hand, arylmethyl chloride derivatives as a family of in-
expensive organic intermediates can be oxidized to aldehydes by
the oxidants,10 thereby serving as new and potential acyl sources,
which would be an important complement to abovementioned
* Corresponding authors. E-mail addresses: yangf@zzu.edu.cn (F. Yang), wyj@zzu.
edu.cn (Y. Wu).
http://dx.doi.org/10.1016/j.tet.2014.11.040
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.
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2
G. Zhang et al. / Tetrahedron xxx (2014) 1e7
methods. Inspired by these previous reports, we envisioned a new,
simple, and efficient synthesis of benzoxazole derivatives by tan-
dem condensation/oxidative reaction of o-aminophenol derivatives
with arylmethyl chlorides under air (Scheme 1c).
in moderate to good yields (Table 2, entries 2e5). Steric effect had an
evident influence and the reaction of 2-methylbenzyl chloride (2b)
only afforded the product in a relatively lower yield of 65% owing to
ortho-methyl group in the benzene ring (Table 2, entry 2). Notably, the
oxidant-sensitive vinyl group could be well tolerated and the product
was obtained in a satisfying yield of 55% (Table 2, entry 6). However,
electron-withdrawing groups (e.g., COOMe, Br, Cl, F and CN)
substituted benzyl chloride derivatives generated the desired prod-
ucts in relative lower yields than those of substrates bearing electron-
donating groups (Table 2, entries 7e11). Exceptionally, the reaction of
4-bromobenzyl chloride could lead to the product in up to 83% yield
(Table 2, entry 8). Moreover, other aromatic arylmethyl chloride like
1-(chloromethyl)naphthalene (2l) also afforded the desired product
in a good yield of 82% (Table 2, entry 12).
To further establish the scope of this reaction, some substituted
o-aminophenol derivatives were then screened (Table 3). Under the
optimized reaction conditions, o-aminophenol possessing a methyl
group at meta- or para-position gave the corresponding desired
products in yields of 71% and 80%, respectively (Table 3, entries 1
and 2). 2-Amino-4-methoxyphenol (1d) and 3-amino-2-naphthol
(1e) could also give the corresponding products in moderate
yields after prolonged reaction time (Table 3, entries 3 and 4). The
electron-poor substrate 1f was also tolerated and gave the product
in a moderate yield of 46% in the presence of FeCl2 as an additive
(Table 3, entry 5). Finally, this reaction could also be applied to the
synthesis of benzothiazole and benzimidazole rings, and gratify-
ingly, the desired products could be obtained in yields of 60% and
85%, respectively (Scheme 2).
2. Results and discussion
In our initial investigation, we performed the model reaction
of o-aminophenol (1a) with benzyl chloride (2a) in the presence
of KNO3 as oxidant and Cu(OAc)2 as catalyst in toluene at 140 ꢀC
under air, and the desired product could be obtained in 25%
isolated yield (Table 1, entry 1). However, base effect is remark-
able in this reaction. For example, when the bases such as K2CO3,
KHCO3, NaHCO3 and KF were added to the above catalytic system,
only trace amount of desired product was detected in the pres-
ence of K2CO3, NaHCO3 and KF; to the contrary, KHCO3 as the best
base could afford the product in 66% yield (Table 1, entries 2e5).
Increasing the loading of KNO3 to 4.0 equiv or decreasing the
reaction temperature to 120 ꢀC did not improve the catalytic
process (Table 1, entries 6 and 7). Then, some other solvents (e.g.,
1,4-dioxane, DMSO, xylene, DMF, bromobenzene and chloroben-
zene) were evaluated, and to our surprise, the reaction in chlo-
robenzene could give an up to 77% yield (Table 1, entries 8e13).
Using DDQ and BQ as the oxidant or performing the reaction
under an oxygen atmosphere did not generate the product in
higher yields (Table 1, entries 14e16). Finally, some commercially
available copper catalysts such as Cu(OTf)2, CuCl2 and CuBr2 were
also screened, and unfortunately, all of them did not exhibit
higher catalytic activity (Table 1, entries 17e19). In addition, the
desired product was not detected at all under the copper-free
conditions (Table 1, entry 20).
Mechanistic studies were explored to obtain a deeper insight
intothe reactionprocess. The reaction of benzyl chloride (2a) with o-
aminophenol in the presence of KNO3 under copper-free conditions
Table 1
Optimization of the reaction conditionsa
Entry
Catalyst
Base
Oxidant
Solvent
Yield (%)b
1
2
3
4
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OTF)2
CuCl2
d
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
KNO3
DDQ
BQ
O2
KNO3
KNO3
KNO3
KNO3
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Dioxane
DMSO
Xylene
DMF
PhBr
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
25
<5
66
<5
<5
65
30
11
10
23
18
43
77
<5
<5
53
57
36
34
<5
K2CO3
KHCO3
NaHCO3
KF
5
6c
7d
8
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
9
10
11
12
13
14
15
16
17
18
19
20
CuBr2
d
PhCl
Bold represents the optimal conditions.
a
Reaction conditions: 1a (0.4 mmol), 2a (0.8 mmol), oxidant (3.0 equiv), base (2.0 equiv), catalyst (20 mol %) in solvent (1.0 mL) at 140 ꢀC for 20 h under air.
Isolated yield.
KNO3 (4 equiv).
At 120 ꢀC.
b
c
d
With theseoptimized reactioncondition inhand, wefirstexplored
resulted in the production of benzaldehyde in 73% yield
(Scheme 3a). Taking benzaldehyde (0.6 mmol) instead of benzyl
chloride under optimized conditions without KHCO3 could afford
the product (3a) in 70% yield (Scheme 3b). The results reveals that
the reaction scope of arylmethyl chlorides, and the results were
summarized in Table 2. The substrates bearing an electron-donating
group such as Me and OMe could give the corresponding products
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G. Zhang et al. / Tetrahedron xxx (2014) 1e7
3
Table 2
Scope of arylmethyl chloridesa
Entry
1
Arylmethyl chloride
Product
Yield (%)b
77
2
65
3
4
81
78
5
82
6
55
54
83
61
53
52
7
8
9
10
11
12
82
a
Reaction conditions: 1a (0.4 mmol), 2 (0.8 mmol), Cu(OAc)2 (20 mol %), KNO3 (3.0 equiv) and KHCO3 (2.0 equiv) in PhCl (1.0 mL) at 140 ꢀC for 20 h under air.
Isolated yield.
b
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G. Zhang et al. / Tetrahedron xxx (2014) 1e7
Table 3
Scope of o-aminophenol derivativesa
Entry
1
o-Aminophenol
Product
Yield (%)b
71
2
80
51
3c
4c
50
46
5d
a
Reaction conditions: 1 (0.4 mmol), 2a (0.8 mmol), Cu(OAc)2 (20 mol %), KNO3 (3.0 equiv) and KHCO3 (2.0 equiv) in PhCl (1.0 mL) at 140 ꢀC for 20 h under air.
Isolated yield.
For 30 h.
FeCl2 (10 mol %) as an additive.
b
c
d
transformation is illustrated in Scheme 4. Firstly, benzyl chloride
(2a) is oxidized to benzaldehyde in the presence of KNO3, accom-
panied by the generation of KCl, CO2 and H2O. Then, an
intermediate imine A is generated from the condensation of
o-aminophenol (1a) with benzaldehyde, which rapidly reaches
equilibrium with another cyclic intermediate dihydrobenzoxazole
B. Finally, the oxidation of the intermediate
B affords 2-
phenylbenzoxazole (3a) as the desired product via the second
oxidative process with the assistance of Cu(OAc)2.
3. Conclusions
Scheme 2. Construction of benzothiazole and benzoimidazole via the condensation/
oxidative reaction.
In summary, we have developed a new approach for the syn-
thesis of 2-arylbenzoxazoles from substituted o-aminophenol and
arylmethyl chlorides as the starting materials. This tandem con-
densation/oxidative reaction could proceed under air utilizing
arylmethyl chlorides as a new and commercially available acyl
source. KNO3 could be employed as low-cost and moderate in-
organic oxidant in this reaction, and various functional groups even
the oxidant-sensitive vinyl group were well tolerated. In addition,
this reaction can also be applied to the synthesis of benzimidazoles
and benzothiazoles.
the catalytic system is effective for the reaction of aldehydes with o-
aminophenols, and the generation of aldehyde in the presence of
KNO3 is the key step in the reaction progress. In addition, only trace
amount of benzoxazole (3a) was observed under copper-free
conditions, accompanied by the generation of an imine (A) and
a dihydrobenzoxazole (B) in yields of 15% and 45%, respectively
(Scheme 3c). The existence of imine (A) and dihydrobenzoxazole (B)
reveals that the condensation still takes place without the assistance
of the catalyst and copper plays a key role for oxidizing dehydro-
genative step form dihydrobenzoxazole to benzoxazole (3a).
Reaction conditions: (a): 2a (0.8 mmol), KNO3 (0.8 mmol), and
KHCO3 (0.8 mmol) in PhCl (1.0 mL) at 140 ꢀC for 20 h under air. (b):
Benzaldehyde (0.56 mmol) instead of benzyl chloride, and KNO3
(0.4 mmol) under optimized conditions without KHCO3. (c): Under
optimized conditions in the absence of Cu catalyst.
4. Experimental
4.1. General information
1H and 13C NMR spectra were recorded on a Bruker DPX-400
spectrometer with CDCl3 or DMSO-d6 as the solvent and TMS as
an internal standard. Melting points were measured using a WC-1
microscopic apparatus and are uncorrected. Mass spectra were
On the basis of the above-mentioned results and the
previous reports,5e7,9 a tentative mechanism to account for this
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G. Zhang et al. / Tetrahedron xxx (2014) 1e7
5
Scheme 3. Controlled experiments.
Scheme 4. Plausible mechanism.
measured on an LC-MSD-Trap-XCT instrument. High resolution
mass spectra were ensured on a MALDI-FTMS. Dichloromethane,
ethyl acetate and hexane were used for column chromatography
without further purification. Other solvents were purified accord-
ing to the standard methods. Reagents were obtained from com-
mercial sources and used without further purification.
solvent in vacuo, the residue was purified by column chromatog-
raphy (ethyl acetate/hexane) to afford the pure product.
4.2.1. 2-Phenylbenzo[d]oxazole (3a). White solid (60 mg, 77%), mp
1
79e80 ꢀC; H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼7.34e7.39 (m, 2H),
7.52e7.61 (m, 4H), 7.77e7.81 (m, 1H), 8.26e8.29 (m, 2H); 13C NMR
(100 MHz, CDCl3, 25 ꢀC):
d¼110.6, 120.0, 124.6, 125.1, 127.2, 127.6,
4.2. General procedure for copper-catalyzed synthesis of 2-
arylbenzoxazoles from o-aminophenol derivatives with ar-
ylmethyl chlorides
128.9, 131.6, 142.1, 150.8, 163.1; HRMS-ESI (m/z): calcd for C13H10NO
[MþH]þ 196.0757, found 196.0752.
4.2.2. 2-o-Tolylbenzo[d]oxazole (3b). White solid (54 mg, 65%), mp
To a solution of o-aminophenol (0.4 mmol) in PhCl (1.0 mL),
arylmethyl chloride (0.8 mmol), Cu(OAc)2 (0.08 mmol), KHCO3
(0.8 mmol), and KNO3 (1.2 mmol) were added. The resulting mix-
ture was heated at 140 ꢀC for 20 h under air unless otherwise noted.
After the reaction was complete and cooling to room temperature,
the mixture was added into H2O (25 mL) and extracted with ethyl
acetate (10 mL) for three times. The combined organic layer was
dried over anhydrous Na2SO4 and filtered. After removal of the
64e66 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼2.81 (s, 3H),
7.31e7.42 (m, 5H), 7.55e7.60 (m, 1H), 7.78e7.82 (m, 1H), 8.16e8.18
(m, 1H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼23.5, 111.8, 121.5, 125.7,
126.3, 127.4, 127.6, 131.3, 132.2, 133.1, 140.2, 143.5, 151.6, 164.7; HRMS-
ESI (m/z): calcd for C14H12NO [MþH]þ 210.0913, found 210.0909.
4.2.3. 2-m-Tolylbenzo[d]oxazole (3c). White solid (68 mg, 81%), mp
79e80 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d¼2.43 (s, 3H),
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6
G. Zhang et al. / Tetrahedron xxx (2014) 1e7
7.31e7.35 (m, 3H), 7.37e7.41 (m, 1H), 7.53e7.57 (m, 1H), 7.74e7.78
(m,1H), 8.04 (d, J¼7.7 Hz,1H), 8.08 (s,1H); 13C NMR (100 MHz, CDCl3,
d
¼7.38e7.44 (m, 2H), 7.60e7.62 (m, 1H), 7.81 (d, J¼8.4 Hz, 3H), 8.35
(d, J¼8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
¼109.9, 113.8,
d
25 ꢀC):
d
¼22.7, 111.9, 121.3, 125.8, 126.1, 126.3, 128.3, 129.5, 130.1,
117.2, 119.6, 124.1, 125.2, 127.0, 130.1, 131.7, 140.9, 149.9, 159.9;
HRMS-ESI (m/z): calcd for C14H9N2O [MþH]þ 221.0709, found
221.0704.
133.7, 140.0, 143.4, 152.0, 164.6; HRMS-ESI (m/z): calcd for C14H12NO
[MþH]þ 210.0913, found 210.0909.
4.2.4. 2-p-Tolylbenzo[d]oxazole (3d). White solid (65 mg, 78%), mp
4.2.12. 2-(Naphthalen-1-yl)benzo[d]oxazole (3l). White solid (80 mg,
82%), mp 104e106 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
116e118 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼2.43 (s, 3H),
7.31e7.36 (m, 4H), 7.54e7.57 (m, 1H), 7.74e7.78 (m, 1H), 8.14 (d,
d
¼7.36e7.38 (m, 2H), 7.54e7.62 (m, 3H), 7.67e7.71 (m, 1H),
J¼8.1 Hz, 2H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼22.9, 111.8, 121.1,
7.86e7.91 (m, 2H), 7.99 (d, J¼8.2 Hz, 1H), 8.40 (d, J¼7.2 Hz, 1H), 9.46
125.7, 125.8, 126.2, 128, 9, 130.9, 143.4, 143.5, 152.0, 164.6; HRMS-ESI
(d, J¼8.6 Hz, 1H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
¼109.5, 119.3,
d
(m/z): calcd for C14H12NO [MþH]þ 210.0913, found 210.0910.
122.5, 123.5, 123.9, 124.3, 125.3, 125.4, 126.9, 127.7, 128.3, 129.7, 131.3,
132.9, 141.3, 149.1, 161.8; HRMS-ESI (m/z): calcd for C17H12NO
[MþH]þ 246.0913, found 246.0907.
4.2.5. 2-(3-Methoxyphenyl)benzo[d]oxazole
(74 mg, 82%), mp 72e74 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
¼3.86 (s, 3H), 7.03 (dd, J¼1.8, 8.3 Hz, 1H), 7.29e7.34 (m, 2H),
(3e). White
solid
d
4.2.13. 6-Methyl-2-phenylbenzo[d]oxazole
(3m). White
solid
7.35e7.39 (m, 1H), 7.52e7.54 (m, 1H), 7.75e7.77 (m, 2H), 7.81 (d,
(59 mg, 71%), mp 93e95 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
J¼7.6 Hz,1H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼56.7,111.9,113.2,
d
¼2.50 (s, 3H), 7.16 (d, J¼8.1 Hz, 1H), 7.37 (s, 1H), 7.50e7.52 (m, 3H),
119.5, 121.3, 121.4, 125.9, 126.4, 129.6, 131.3, 143.4, 152.0, 161.2,
164.2; HRMS-ESI (m/z): calcd for C14H12NO2 [MþH]þ 226.0863,
found 226.0857.
7.64 (d, J¼8.1 Hz,1H), 8.22e8.24 (m, 2H); 13C NMR (100 MHz, CDCl3,
25 ꢀC):
d¼20.8, 109.8, 118.4, 124.8, 126.4, 126.5, 127.9, 130.3, 134.6,
139.0, 150.1, 161.6; HRMS-ESI (m/z): calcd for C14H12NO [MþH]þ
210.0913, found 210.0909.
4.2.6. 2-(4-Vinylphenyl)benzo[d]oxazole (3f). White solid (49 mg,
1
55%), mp 82e84 ꢀC; H NMR (400 MHz, CDCl3, 25 ꢀC):
d¼5.36 (d,
4.2.14. 5-Methyl-2-phenylbenzo[d]oxazole
(3n). White
(67 mg, 80%), mp 102e104 ꢀC; H NMR (400 MHz, CDCl3, 25 ꢀC):
¼2.47 (s, 3H), 7.13e7.15 (m, 1H), 7.43 (d, J¼8.3 Hz, 1H), 7.50e7.51
(m, 3H), 7.55 (s, 1H), 8.22e8.25 (m, 2H); 13C NMR (100 MHz, CDCl3,
solid
1
J¼10.9 Hz, 1H), 5.86 (d, J¼17.6 Hz, 1H), 6.71e6.78 (dd, J¼10.9,
17.6 Hz, 1H), 7.32e7.35 (m, 2H), 7.52e7.56 (m, 3H), 7.75e7.77 (m,
1H), 8.19 (d, J¼8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
d
¼109.6, 115.0, 119.0, 123.6, 124.1, 125.3, 125.7, 126.9, 135.1, 139.6,
25 ꢀC):
d
¼20.5, 108.9, 119.0, 125.2, 126.4, 126.6, 127.9, 130.4, 133.4,
141.2, 149.8, 161.9; HRMS-ESI (m/z): calcd for C15H12NO [MþH]þ
141.4, 148.0, 162.1; HRMS-ESI (m/z): calcd for C14H12NO [MþH]þ
222.0913, found 222.0910.
210.0913, found 210.0910.
4.2.7. Methyl 4-(benzo[d]oxazol-2-yl)benzoate (3g). White solid
(55 mg, 54%), mp 197e199 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
4.2.15. 5-Methoxy-2-phenylbenzo[d]oxazole
(3o). White
solid
(46 mg, 51%), mp 80e82 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼3.96 (s, 3H), 7.36e7.41 (m, 2H), 7.58e7.61 (m, 1H), 7.79e7.81 (m,
d
¼3.86 (s, 3H), 6.94 (dd, J¼2.6, 8.9 Hz,1H), 7.26 (d, J¼2.3 Hz,1H), 7.45
1H), 8.17e8.19 (m, 2H), 8.33 (d, J¼8.4 Hz, 2H); 13C NMR (100 MHz,
(d, J¼8.9 Hz, 1H), 7.50e7.52 (m, 3H), 8.21e8.24 (m, 2H); 13C NMR
CDCl3, 25 ꢀC):
d¼51.4, 109.8, 119.4, 123.9, 124.7, 126.5, 129.1, 130.0,
(100 MHz, CDCl3, 25 ꢀC):
127.9, 130.4, 142.0, 144.5, 156.4, 162.8; HRMS-ESI (m/z): calcd for
C
d¼54.9, 101.9, 109.7, 112.7, 126.3, 126.5,
131.5, 141.0, 149.9, 160.9, 165.3; HRMS-ESI (m/z): calcd for C15H12NO3
[MþH]þ 254.0812, found 254.0802.
14H12NO2 [MþH]þ 226.0863, found 226.0857.
4.2.8. 2-(4-Bromophenyl)benzo[d]oxazole (3h). White solid (91 mg,
83%), mp 156e158 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
4.2.16. 2-Phenylnaphtho[2,3-d]oxazole (3p). White solid (49 mg,
50%), mp 201e203 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d¼7.41e7.46
d
¼7.35e7.37 (m, 2H), 7.56e7.58 (m, 1H), 7.67 (d, J¼8.5 Hz, 2H),
(m, 2H), 7.50e7.52 (m, 3H), 7.89e7.91 (m, 2H), 7.94e7.97 (m,1H), 8.16
7.75e7.78 (m, 1H), 8.12 (d, J¼8.5 Hz, 2H); 13C NMR (100 MHz, CDCl3,
(s, 1H), 8.29e8.31 (m, 2H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
25 ꢀC):
d
¼109.7, 119.1, 123.8, 124.4, 125.1, 125.2, 128.0, 131.2, 141.0,
d
¼105.3, 116.4, 123.6, 124.4, 126.1, 126.9, 127.2, 127.5, 127.9, 130.6,
149.8, 161.1; HRMS-ESI (m/z): calcd for C13H9BrNO [MþH]þ
130.8, 131.0, 141.2, 148.8, 164.0; HRMS-ESI (m/z): calcd for C17H12NO
[MþH]þ 246.0913, found 246.0906.
273.9862, found 273.9853.
4.2.9. 2-(4-Chlorophenyl)benzo[d]oxazole (3i). White solid (56 mg,
4.2.17. 5-chloro-2-phenylbenzo[d]oxazole (3q). White solid (42 mg,
61%), mp 150e152 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼7.31e7.33
(m, 2H), 7.42e7.44 (m, 2H), 7.50e7.52 (m, 1H), 7.72e7.75 (m,
1H), 8.11e8.13 (m, 2H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
46%), mp 99e101 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼7.26e7.29
(m, 1H), 7.43e7.54 (m, 4H), 7.71 (d, J¼1.1 Hz, 1H), 8.18e8.20 (m, 2H);
13C NMR (100 MHz, CDCl3, 25 ꢀC):
¼110.2, 119.0, 124.3, 125.7, 126.7,
d¼109.6,
d
119.1, 123.7, 124.3, 124.6, 127.8, 128.2, 136.7, 141.0, 149.7, 161.0;
HRMS-ESI (m/z): calcd for C13H9ClNO [MþH]þ 230.0367, found
230.0361.
127.9, 129.0, 130.9, 142.3, 148.3, 163.3; HRMS-ESI (m/z): calcd for
C
13H9ClNO [MþH]þ 230.0367, found 230.0361.
4.2.18. 2-Phenylbenzo[d]thiazole (3r). Light yellow solid (51 mg,
60%), mp 112e114 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
¼7.36
(t, J¼7.6 Hz, 1H), 7.46e7.49 (m, 4H), 7.87 (d, J¼8.0 Hz, 1H),
8.06e8.09 (m, 3H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
122.3, 124.2, 125.3, 126.6, 128.0, 130.0, 132.7, 134.1, 153.2, 167.1;
HRMS-ESI (m/z): calcd for C13H10NS [MþH]þ 212.0528, found
212.0523.
4.2.10. 2-(4-Fluorophenyl)benzo[d]oxazole (3j). White solid (46 mg,
d
53%), mp 94e96 ꢀC; 1H NMR (400 MHz, CDCl3, 25 ꢀC):
d
¼7.12e7.16
(m, 2H), 7.27e7.33 (m, 2H), 7.49e7.51 (m, 1H), 7.71e7.74
d
¼120.6,
(m, 1H), 7.17e7.20 (m, 2H); 13C NMR (100 MHz, CDCl3, 25 ꢀC):
d
¼109.5, 115.1 (d, J¼22.1 Hz), 119.0, 122.4 (d, J¼3.2 Hz), 123.6, 124.1,
128.8 (d, J¼8.8 Hz), 141.0, 149.7, 161.0, 163.7 (d, J¼251.1 Hz);
HRMS-ESI (m/z): calcd for C13H9FNO [MþH]þ 214.0663, found
214.0655.
4.2.19. 2-Phenyl-1H-benzo[d]imidazole (3s). White solid (66 mg,
85%), mp 288e290 ꢀC; 1H NMR (400 MHz, DMSO-d6, 25 ꢀC):
4.2.11. 4-(Benzo[d]oxazol-2-yl)benzonitrile (3k). Light yellow solid
d
¼7.23e7.25 (m, 2H), 7.49e7.65 (m, 5H), 8.25 (d, J¼7.5 Hz, 2H),
1
(46 mg, 52%), mp 202e204 ꢀC; H NMR (400 MHz, CDCl3, 25 ꢀC):
12.97 (broad s, 1H); 13C NMR (100 MHz, DMSO-d6, 25 ꢀC):
d¼121.6,
Please cite this article in press as: Zhang, G.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.11.040

G. Zhang et al. / Tetrahedron xxx (2014) 1e7
7
Fenner, S. Angew. Chem., Int. Ed. 2009, 48, 201; (i) Sames, D.; Sezen, B.; Lane, B. S.
PCT Int. Appl. WO 2004069394 A2 2004. (j) Wynne, G. M.; Wren, S. P.; Johnson,
P. D.; Price, D.; De Moor, O.; Nugent, G.; Tinsley, J. M.; Storer, R.; Mulvaney, A.;
Pye, R. J.; Dorgan, C. R. PCT Int. Appl. WO 2007091106 A2 2007. (k) Yuan, Y.;
126.0, 128.4, 129.3, 129.7, 150.8; HRMS-ESI (m/z): calcd for C13H11N2
[MþH]þ 195.0917, found 195.0912.
ꢀ
Thome, I.; Kim, S. H.; Chen, D. T.; Beyer, A.; Bonnamour, J.; Zuidema, E.; Chang,
Acknowledgements
S.; Bolm, C. Adv. Synth. Catal. 2010, 352, 2892; (l) Wu, M. Y.; Hu, X.; Liu, J.; Liao,
Y. F.; Deng, G. J. Org. Lett. 2012, 14, 2722; (m) Cao, X. X.; Cheng, X. F.; Bai, Y.; Liu,
S. W.; Deng, G. J. Green. Chem. 2014, 16, 4644.
We are grateful to the National Natural Science Foundation of
China (Nos. 21102134, 21172200 and J1210060) for financial sup-
port to this research.
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Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.11.040.
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Please cite this article in press as: Zhang, G.; et al., Tetrahedron (2014), http://dx.doi.org/10.1016/j.tet.2014.11.040