p-Toluenesulfonic acid-catalyzed metal-free formal [4?+?1] heteroannulation via N[sbnd]H/O[sbnd]H/S[sbnd]H functionalization: One-pot access to 2-aryl/hetaryl/alkyl benzazole derivatives

Article abstract of DOI:10.1016/j.tet.2016.12.073

A concise and direct one-pot [4?+?1] synthetic strategy for the construction of 2-substituted benzazoles such as benzoxazoles and benzothiazoles has been disclosed in high yields (80–98%) by cascade coupling reaction of 2-amino(thio)phenols with β-oxodithioesters. The current approach enables N[sbnd]H/O[sbnd]H/S[sbnd]H functionalization in one-pot under solventless condition leading to diverse benzazoles without use of any external metal. A wide range of 2-amino(thio)phenols and β-oxodithioesters are compatible toward this transformation with excellent functional group tolerance. Furthermore, we preempt the wider implications of this novel strategy by demonstrating its compatibility toward versatile diversification of DNA Topoisomerase-II inhibitors.

Full text of DOI:10.1016/j.tet.2016.12.073

Accepted Manuscript
p-Toluenesulfonic acid-catalyzed metal-free formal [4 + 1] heteroannulation via
N-H/O-H/S-H functionalization: One-pot access to 2-aryl/hetaryl/alkyl benzazole
derivatives
Abhijeet Srivastava, Gaurav Shukla, Maya Shankar Singh
PII:
S0040-4020(16)31379-5
10.1016/j.tet.2016.12.073
TET 28365
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 July 2016
Revised Date: 26 December 2016
Accepted Date: 29 December 2016
Please cite this article as: Srivastava A, Shukla G, Singh MS, p-Toluenesulfonic acid-catalyzed metal-
free formal [4 + 1] heteroannulation via N-H/O-H/S-H functionalization: One-pot access to 2-aryl/hetaryl/
alkyl benzazole derivatives, Tetrahedron (2017), doi: 10.1016/j.tet.2016.12.073.
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ACCEPTED MANUSCRIPT
Graphical Abstract
p-Toluenesulfonic acid-catalyzed metal-free formal
[4 + 1] heteroannulation via N-H/O-H/S-H
functionalization: one-pot access to 2-aryl/hetaryl/alkyl
benzazole derivatives
Leave this area blank for abstract info.
Abhijeet Srivastava, Gaurav Shukla and Maya Shankar Singh

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
p-Toluenesulfonic acid-catalyzed metal-free formal [4 + 1] heteroannulation via N-
H/O-H/S-H functionalization: one-pot access to 2-aryl/hetaryl/alkyl benzazole
derivatives
Abhijeet Srivastava, Gaurav Shukla and Maya Shankar Singh
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A concise and direct one-pot [4 + 1] synthetic strategy for the construction of 2-substituted
benzazoles such as benzoxazoles and benzothiazoles has been disclosed in high yields (80 to
98%) by cascade coupling reaction of 2-amino(thio)phenols with β-oxodithioesters. The current
approach enables N-H/O-H/S-H functionalization in one-pot under solventless condition leading
to diverse benzazoles without use of any external metal. A wide range of 2-amino(thio)phenols
and β-oxodithioesters are compatible toward this transformation with excellent functional group
tolerance. Furthermore, we preempt the wider implications of this novel strategy by
demonstrating its compatibility toward versatile diversification of DNA Topoisomerase-II
inhibitors.
Available online
Keywords:
β-Oxodithioesters
2-Amino(thio)phenols
p-Toluenesulfonic acid
Heteroannulation
Benzoxazoles
2016 Elsevier Ltd. All rights reserved
.
Benzothiazoles
Solventless
1. Introduction
Due to increasing environmental burden, the development of
operationally simple and eco-compatible strategies that provide
high synthetic efficiency involving pot/atom/step/cost economy
(PASCE) has been an important goal of synthetic chemistry, and
continues to be a great challenge. In this regard, cascade
processes that incorporate multiple bond-forming events in one-
pot have come into play, and are of paramount interest in organic
syntheses.1 Benzazoles such as benzoxazoles, benzothiazoles and
benzimidazoles represent an important class of fused-
heterocycles, and are the ubiquitous structural motifs and
building blocks in numerous natural products, biologically active
alkaloids, functional materials, and pharmaceuticals.2
Of particular interests are 2-substituted benzazole derivatives,
which are unique pharmacophores and are well known in drug
discovery due to their significant biological activities such as
inhibition of fatty acid amide hydrolase,3a-c cysteine protease,3d
and channel activating protease inhibitors.3e In addition,
benzoxazoles and benzothiazoles are important structural motifs
prominently found in numerous natural products and
commercially available drugs.4a-f Functional chemicals such as
polybenzoxazole (PBO) has long been developed for use as super
engineering plastics and fluorescent 2,5-bis(benzoxazol-2-
yl)thiophene, which is known to be utilized as an optical
brightener for textiles.4g The compounds shown here are a very
few selected examples of already commercialized materials (Fig.
1).
Furthermore, benzoxazoles are recognized as an important
scaffold in fluorescent probes such as anion and metal cation
sensors,5a,b and indispensible building blocks/intermediates for
chemical syntheses.5c On the other hand, it is well documented
that benzothiazole derivatives can be found in drugs used to treat
diabetes, epilepsy, Alzheimer’s disease, cervical cancer or
bacterial infections.6a-h The most emblematic representative of
this class of compound is undoubtedly riluzole, which is a
classical treatment of amyotrophic lateral sclerosis (ALS), a
lethal neurodegenerative disease.6i Notably, SAR (structure–
activity relationship) studies revealed that the change at C-2
position commonly leads to the change in their bioactivity.7
Owing to their privileged status and great importance in
biological and other relevant fields, they have drawn tremendous
attention of synthetic, medicinal, and material chemists.
Classical approaches to benzoxazole derivatives involve two
types of reactions. One is the metal-catalyzed intramolecular
cyclization of o-haloanilides. The second approach mainly
involves the condensation of 2-aminophenol with either a
carboxylic acid derivative under strong acid/high temperature
conditions or an aromatic aldehyde under strong oxidative
conditions. These approaches rely on the efficiency of initial
nucleophilic attack by the aniline moiety at an activated carbonyl
———
Corresponding author. Tel.: +91-542-670-2502; e-mail: mayashankarbhu@gmail.com

2
Tetrahedron
ACCEPTED MANUSCRIPT
group. During past years, numerous methods to access
To the best of our knowledge, no report on the synthesis of
benzoxazole derivatives employing aldehydes,8a-e imines,8f
carboxylic acids,8g,h acyl halides,8i esters,8j,k orthoesters,8l,m
isocyanides,8n carbon monoxide,8o 1,1-dibromoalkenes,8p
nitroalkanes,8q amides,9a,b nitriles,9c alcohols,9d amines,9e
alkynes,9f,g and trithiocyclopropenium ion9h have been reported.
benzazoles utilizing β-oxodithioesters is known to date. Keeping
in mind the utility and importance of solvent-free synthetic
protocols for the synthesis of useful compounds,12a-c herein we
report an operationally simple and efficient approach to diverse
2-substituted benzoxazoles/benzothiazoles under solventless
condition12d in the absence of any external metal (Scheme 2).
Scheme 2. Synthesis of 2-substituted benzoxazoles/
benzothiazoles.
2. Results and discussion
The demand for improved synthetic methods towards
heterocyclic scaffolds and their derivatives is high and
continuous. The vast biological importance of benzazole
derivatives inspired us to develop a simple and efficient protocol
for their syntheses. The presence of both electrophilic and
nucleophilic sites in a single synthon has great potential in
developing new reaction pathways. One such simple synthon
family is β-oxodithioester, and its utility as versatile
intermediates in organic synthesis has been well recognized.13
Our group has a long standing interest in exploiting the reactivity
of β-oxodithioesters14 which can be paired with a variety of
nucleophiles and electrophiles.
Fig. 1. Examples of bioactive and functional molecules
containing benzazole units.
We began our studies by using 2-aminophenol (1a) and
methyl 3-oxo-3-phenylpropanedithioate (2a) as test substrates.
Initially, the stirring of 1a (1.1 mmol) and 2a (1.0 mmol) under
catalyst and solvent-free conditions at room temperature and 90
0C separately failed to react even after 48 h (Table 1, entries 1
and 2). Next, we performed the above test reaction in the
2-Aminothiophenols upon reaction with carbon disulfide,
sodium sulphide, and various isothiocyanates afforded a wide
range of benzothiazole derivatives.7 Condensation reactions of 2-
aminothiophenols
with
β-diketones,10a,b β-ketonitriles/β-
ketoesters10c,d or α,α-dihaloketones10e to provide benzazoles have
been reported (Scheme 1).
0
presence of 20 mol % of FeCl3 in toluene at 90 C for 20 h
(monitored by TLC). Workup of the reaction mixture provided
the desired product 3aa in 15% yield, and most of the starting
materials remained intact (Table 1, entry 3). The above result
encouraged us to continue our investigations to optimize the
reaction conditions for the formation of 3aa in high yield. In this
context, we carried out a systematic survey of the reaction
conditions and the results are summarized in Table 1. Among the
various Lewis acids such as SbCl3, CuBr2 and In(OTf)3 screened
(Table 1, entries 4-7), 5 mol % of In(OTf)3 provided the desired
product 3aa in 84% isolated yield within 6 h with 88%
conversion of 2a (Table 1, entry 7). Inspired by the above
observation, next we envisioned to screen Brønsted acids.
Among the various Brønsted acids investigated such as
trifluoromethane sulfonic acid (TFA), methane sulfonic acid, p-
toluenesulfonic acid monohydrate (PTSA) under solvent-free
conditions at 90 °C (Table 1, entries 8-12), 10 mol % of PTSA
provided the desired product 3aa in 98% yield with >99%
conversion of 2a (Table 1, entry 11). Decreasing the loading of
PTSA to 5 mol % decreased the yield significantly and increased
the time of the reaction more than two fold (Table 1, entry 12).
Hence, the optimum reaction condition for the synthesis of
benzoxazole 3aa was achieved by employing 1a (1.5 mmol), 2a
(1 mmol), PTSA (10 mol %), at 90°C in open atmosphere in
solventless condition.
Scheme 1. Strategies towards 2-substituted benzazoles.
Notable recent developments to access benzazole derivatives
are by some other groups such as those of Beifuss,11a
Punniyamurthy,11b and ours.11c These methods are undoubtedly
effective but suffer from drawbacks such as requiring microwave
radiation, high temperature, catalysts, multistep syntheses, use of
excess amount of an additive or expensive starting materials
which adversely affect the economics as well as the sustainable
nature of the reactions. Therefore, exploring more economical
and eco-efficient strategies and improvement in the existing
synthetic methods of benzazoles has received considerable
attention and recognized as strategic issues.

3
Table 1
Table 2
ACCEPTED MANUSCRIPT
Optimization of reaction conditions for the synthesis of 2-
Scope of 2-substituted benzoxazoles and benzothiazoles
phenylbenzoxazole 3aaa
PTSA
10 mol %
NH2
O
S
N
Ar
Ar
R
+
90 °C
solventless
no external metal
R
SMe
X
4
XH
1
2
3
,
N
O
N
O
N
Me
OMe
Entry Catalyst
(mol %)
Solvent
T
t
Conversion Yield
b
O
(°C) (h) of 2a (%)
%
3aa
3aa
3ab (98%, 10 h)
(98%, 10 h)
3ac
(98%, 10 h)
c
Me
Me
But
1
none
none
rt
48
48
20
20
20
7
-
>1
35
38
28
82
88
-
-
N
O
N
O
N
O
Cl
Cl
2
none
none
90
90
90
90
90
90
90
90
90
90
90
trace
15
3ae
3ca
3ba
3ce
3dc
3be
(89%, 12 h)
(90%, 12 h)
(98%, 10 h)
3
FeCl3 (20)
SbCl3 (20)
CuBr2 (20)
toluene
toluene
toluene
But
MeO
N
N
N
4
34
Cl
O
O
O
5
23
(95%, 11 h)
(92%, 12 h)
3da
(98%, 10 h)
6
In(OTf)3 (20) toluene
In(OTf)3 (5) toluene
79
MeO
MeO
MeO
OMe
N
N
N
O
Me
Cl
O
7
6
84
c,d
O
3db
3de
(94%, 12 h)
(98%, 10 h)
(98%, 10 h)
8
CF3SO3H (20) toluene
48
30
18
10
22
-
Cl
Me
Cl
N
N
N
9
CH3SO3H (20) -e
70
90
>99
87
66d
88d
98d
82d
Cl
O
O
O
Me
F
e
10
11
12
PTSA (20)
PTSA (10)
PTSA (5)
-
-
-
3ja
3fa
(87%, 14 h)
Cl
3je
(92%, 13 h)
(85%, 15 h)
Cl
e
e
Me
N
O
N
O
N
O
3ag
3bg (91%, 13 h)
3ah (90%, 14 h)
(89%, 14 h)
a
Unless otherwise specified, the reaction conditions are: 2-
aminophenol (1a, 1.1 mmol), methyl 3-oxo-3-
Cl
Cl
Cl
Cl
N
N
N
S
CF3
Me
S
O
phenylpropanedithioate (2a, 1.0 mmol).
b Isolated yield.
c No reaction.
d 1.5 mmol of 1a and 1.0 mmol of 2a were used.
4kd (87%, 6 h)
3ek
4kf
4ka
(92%, 5 h)
(82%, 16 h)
Br
N
Cl
N
O
N
S
N
O
S
Me
O
S
3aj (85%, 14 h)
3ai
(86%, 14 h)
4kk
(90%, 6 h)
(92%, 5 h)
e Solventless condition (few drops of acetonitrile)
Me
Cl
Me
N
S
N
O
O
N
O
S
O
3bi
(87%, 13 h)
3ei
(85%, 15 h)
3bj
3ej
(87%, 14 h)
With the established optimal conditions in hand, we explored
the scope of both substrates 2-aminophenols/2-aminothiophenols
1 and β-oxodithioesters 2. A variety of β-oxodithioesters 2a–2k
proved to be suitable substrates under the optimized reaction
conditions affording the desired benzoxazoles 3 (19 examples)
and benzothiazoles 4 (4 examples) in excellent yields (Table 2),
even performing the reaction on a larger scale (5 mmol). It is
noteworthy that dithioesters 2 bearing the substituents R not only
aromatics (containing both electron-donating as well as electron-
withdrawing substituents) but extended aromatics such as
naphthyl and biphenyl also worked well under our optimized
conditions affording the desired 2-substituted benzoxazoles in
excellent yields (Table 2, 3ag, 3bg, 3ah). Notably, β-
oxodithioester 2k bearing the substituents R as methyl group
upon reaction with 2-aminophenol 1e and 2-aminothiophenol 1k
separately under standard optimized conditions provided the
corresponding 2-methyl benzoxazole 3ek in 82% yield and 2-
methyl benzothiazole 4kk in 92% yield, respectively (Table 2).
To further explore the potential of our methodology, the scope
of β-oxodithioesters 2 bearing heteroaryl groups at R was
investigated (Table 2). As shown in Table 2, the heteroaryl
substituents of β-oxodithioesters 2 did not affect the efficiency of
this transformation, and the desired products were produced in
high yields. We then investigated the direct incorporation of
thienyl and furyl moiety into the benzoxazole (Table 2, 3bi, 3bj,
3ei, 3dj and 3ej) and benzothiazole (Table 2, 4kj) under the
optimized set of reaction conditions, which set the stage for novel
ligand development in transition-metal catalysis in a very step-
economical one-pot fashion.
MeO
Cl
Cl
N
O
O
N
O
O
N
O
S
3dj (94%, 5 h)
(85%, 14 h)
4kj
(90%, 6 h)
Remarkably, this protocol not only tolerated various
functional groups but also incorporated highly sensitive
functional groups such as carboxylic acids, nitro and nitrile into
the benzoxazole moiety, which might prove valuable handles in
post-synthetic transformations (Table 3, 3ga-3ic). To set the
stage for the applicability of the new synthetic method, a variety
of DNA topoisomerase-II inhibitor derivatives were synthesized
in 80-89% yields (Table 4, 3ea-3ee), which proves to the
applicability of this synthetic strategy to the late stage
modification of complex natural products in a high desirable
feature, an analogues of various bioactive molecules that could
be prepared without the need for de novo synthesis.
Following the successful discovery on the tunable synthesis of
diverse 2-substituted benzoxazole/benzothiazoles derivatives, we
designed some control experiments to explore the reaction
mechanism. To shed some light on this cyclization strategy, and
to check the possibility of oxidative cyclization that could occur
at higher temperature, we further treated 4-methyl-2-
aminophenol (1b) with dithioester (2a) under standard reaction
conditions in the presence of TEMPO (1 equiv).

4
Tetrahedron
Table 3
The structures of all the synthesized benzoxazoles 3 were
ACCEPTED MANUSCRIPT
characterized by their satisfactory spectral (1H, 13C, 19F NMR and
Functional group tolerance
HRMS) studies and unambiguously established by the single
crystal X-ray diffraction analysis of one of the representative
compound 3ed (Fig. 2).15
Fig. 2. ORTEP diagram of 3ed.
Our all efforts to synthesize benzimidazole derivatives from 2-
aminoanilines following optimized reaction conditions for 3 & 4
were less satisfactory.19 However, treatment of 1.5 mmol of 4-
bromo-2-aminoaniline (1l) and 1.0 mmol of ethyl 3-(p-
methoxyphenyl)oxopropanedithioate (2l) in 1mL of acetonitrile
Table 4
Synthesis of DNA topoisomerase-II inhibitors
at 90 °C for 15
h afforded the desired 5-bromo-2-(p-
methoxyphenyl)benzimidazole (5ll) in 46% isolated yield.
A plausible mechanism for the Brønsted acid catalyzed
cyclization reactions of 2-amino(thio)phenols with β-
oxodithioester is shown in Scheme 4. The Brønsted acid
catalyzed condensation reaction of 1 with 2 would take place to
generate a ketimine intermediate A. Ketiminium intermediate B
would be generated in the presence of TsOH.H2O. The
intramolecular nucleophilic addition of
B would produce
intermediate C, which undergoes selective Csp3−Csp3 bond
cleavage16 to produce the desired benzazoles 3 and 4 with the
elimination of one molecule of methyl dithioacetate (Scheme 4).
The reaction proceeded smoothly providing the desired
benzoxazole (3ba) in 96% isolated yield (Scheme 3),11b which is
comparable to the yield obtained in the absence of TEMPO,
suggesting that the reaction does not involve the radical
cyclization pathway (Scheme 3, eqn. 1). Further, when 1.0 equiv
of radical trapping reagent BHT was added to the standard
reaction system, the desired product benzoxazole (3ba) was
isolated in 96% yield (Scheme 3, eqn. 2).
Scheme 4. A plausible mechanism.
3. Conclusion
In summary, we have developed a general, operationally
simple and efficient one-pot cascade method to construct diverse
2-aryl/hetaryl/alkyl benzazoles from inexpensive and readily
available 2-amino(thio)phenols catalyzed by Brønsted acid p-
toluenesulfonic acid. A broad range of aromatic, heteroaromatic,
and aliphatic β-oxodithioesters participated smoothly toward this
protocol. During the transformation, two new bonds are formed
via challenging N-H/O-H and N-H/S-H functionalization. The
available substrates and easy mode of operation make it very
practical for the synthesis of diverse 2-substituted benzoxazole
and benzothiazole derivatives. The present findings not only
provide a general and concise method for the preparation of 2-
heteroaryl substituted benzazoles but also a diverse synthesis of
DNA topoisomerase-II inhibitor derivatives.
Scheme 3. Mechanistic studies.a
aYields refer to the isolated yields.

5
4. Experimental section
4.1. General Information
8.21 (dd, J = 6.0 Hz, 3.0 Hz, 2H), 7.54–7.40 (m, 5H), 7.15–7.10
ACCEPTED MANUSCRIPT
(m, 3H), 2.47 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 163.2,
149.0, 142.3, 134.4, 131.3, 128.8, 127.5, 127.3, 126.2, 119.9,
109.9, 21.3.
2-Amino(thio)phenols 1 were commercially available and
used as received without further purification. β-Oxodithioesters 2
were prepared following the known procedure.14b Thin-layer
chromatography (TLC) was performed using silica gel 60 F254
precoated plates and visualization was achieved by ultraviolet
light at 254 nm. Except where otherwise noted, all reactions were
carried out in 10 mL round bottom flask under open atmosphere.
1H, 13C and 19F NMR spectra were recorded on 300 or 500 MHz
spectrometers. Chemical shifts were given in parts per million
(ppm, δ), referenced to the peak of tetramethylsilane. Coupling
constants are quoted in Hz (J). High-resolution mass spectra were
obtained using a high-resolution ESI-TOF mass spectrometer.
4.2.6. 5-Methyl-2-(p-chlorophenyl)benzoxazole (3be). Obtained
(1/99 ethyl acetate/hexane) as a white solid (216.90 mg, 89%
yield); mp 150.0–152.0 °C (lit.17k 148.0–150.0 °C); 1H NMR
(300 MHz, CDCl3) δ 8.14 (d, J = 8.1 Hz, 2H), 7.52–7.36 (m, 5H),
7.14 (d, J = 7.5 Hz, 1H), 2.47 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 162.0, 148.9, 142.1, 137.5, 134.5, 129.8, 129.1, 128.7,
127.9, 126.4, 125.7, 119.9, 109.9, 21.4.
4.2.7. 5-tert-Butyl-2-phenylbenzoxazole (3ca). Obtained (1/99
ethyl acetate/hexane) as a white solid (238.80 mg, 95% yield);
1
mp 83.0–85.0 °C (lit.17c 83.0–84.0 °C); H NMR (300 MHz,
CDCl3): δ 8.26 (m, 2H), 7.80 (d, J = 3.0 Hz, 1H), 7.53–7.50 (m,
3H), 7.48 (s, 1H), 7.43–7.39 (m, 1H), 1.40 (s, 9H); 13C NMR (75
MHz, CDCl3) δ 163.2, 148.8, 148.2, 142.0, 131.4, 128.9, 127.6,
127.4, 122.9, 116.5, 109.7, 34.8, 31.6.
4.2. General Procedure for Compounds 3 and 4
A mixture of 2-amino(thio)phenols (1, 1.5 mmol) and β-
oxodithioesters (2, 1.0 mmol) were placed in 10 mL round
bottom flask. p-Toluenesulfonic acid monohydrate (PTSA) (10
mol %) and 1mL of acetonitrile was added to make homogenous
paste. The mixture was stirred at 90 °C for stipulated period of
time (in open atmosphere). After the completion of the reaction
(monitored by TLC), the reaction mixture was quenched with
H2O and extracted with EtOAc. The organic layer was separated,
washed with water twice, dried over anhydrous Na2SO4, and
concentrated under reduced pressure. The crude reaction mixture
was purified by column chromatography on silica gel (100−200
mesh) using ethyl acetate/hexanes as the eluting system. The
4.2.8.
5-tert-Butyl-2-(p-chlorophenyl)benzoxazole
(3ce).17e
Obtained (1/99 ethyl acetate/hexane) as a white solid (262.90 mg,
1
92% yield); mp 155.0–157.0 °C; H NMR (300 MHz, CDCl3) δ
8.16 (d, J = 9.0 Hz, 2H), 7.79 (s, 1H), 7.50–741 (m, 4H), 1.40 (s,
9H); 13C NMR (75 MHz, CDCl3) δ 162.2, 148.8, 148.4, 142.0,
137.6, 129.3, 128.8, 125.9, 123.1, 116.6, 109.7, 34.8, 31.6.
4.2.9. 5-Methoxy-2-phenylbenzoxazole (3da). Obtained (2/98
ethyl acetate/hexane) as a white solid (220.74 mg, 98% yield);
1
mp 60.0–62.0 °C (lit.17d 60.0–61.0 °C); H NMR (300 MHz,
CDCl3) δ 8.25–8.22 (m, 2H), 7.53–7.51 (m, 3H), 7.45 (d, J = 9.0
Hz, 1H), 7.27 (s, 1H), 6.94 (d, J = 9.0 Hz, 1H), 3.87 (s, 3H); 13
C
1
identity and purity of product was confirmed by H, 13C, 19F
NMR (75 MHz, CDCl3) δ 163.9, 157.5, 145.5, 143.0, 131.4,
128.9, 127.5, 127.3, 113.7, 110.7, 102.9, 55.8.
NMR spectroscopic and MS/HRMS analysis.
4.2.1. 2-Phenylbenzoxazole (3aa). Obtained (1/99 ethyl
acetate/hexane) as a white solid (191.31 mg, 98% yield); mp
100.0–102.0 °C (lit.8b 101.0–102.0 °C); 1H NMR (300 MHz,
CDCl3) δ 8.28–8.25 (m, 2H), 7.79–7.77 (m, 1H), 7.60–7.50 (m,
4H), 7.37–7.34 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 163.1,
150.9, 142.2, 131.5, 128.9, 127.7, 127.2, 125.1, 124.6, 120.0,
110.6.
4.2.10. 5-Methoxy-2-(p-tolyl)benzoxazole (3db). Obtained (2/98
ethyl acetate/hexane) as a white solid (234.48 mg, 98% yield);
mp 113.0–115.0 °C (lit.17h 114.2–115.6 °C); 1H NMR (300 MHz,
CDCl3) δ 8.11 (d, J = 9.0 Hz, 2H), 7.43 (d, J = 9.0 Hz, 1H), 7.31
(d, J = 9.0 Hz, 2H), 7.24 (s, 1H), 6.92 (d, J = 9.0 Hz, 1H), 3.87
(s, 3H), 2.43 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.2, 157.4,
145.4, 142.0, 129.7, 127.5, 124.6, 113.4, 110.6, 102.9, 55.9, 21.5.
4.2.2. 2-(p-Tolyl)benzoxazole (3ab). Obtained (1/99 ethyl
acetate/hexane) as a white solid (205.06 mg, 98% yield); mp
123.0–125.0 °C (lit.8b 122.0–123.0 °C); 1H NMR (300 MHz,
CDCl3) δ 8.15 (d, J = 9.0 Hz, 2H), 7.77–7.74 (m, 1H), 7.58–7.55
(m, 1H), 7.36–7.32 (m, 4H), 2.55 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 162.8, 150.6, 143.6, 142.1, 127.8, 125.7, 124.9, 124.5,
123.4, 119.8, 110.4, 15.0.
4.2.11. 5-Methoxy-2-(p-methoxyphenyl)benzoxazole (3dc).17i
Obtained (3/97 ethyl acetate/hexane) as a white solid (250.16 mg,
1
98% yield); mp 130.0–132.0 °C; H NMR (300 MHz, CDCl3) δ
8.15 (d, J = 8.4Hz, 2H), 7.40 (d, J = 8.7Hz, 1H), 7.23 (d, J = 12.0
Hz, 1H), 7.01–6.87 (m, 3H), 3.87 (s, 3H), 3.85 (s, 3H); 13C NMR
(75 MHz, CDCl3) δ 163.9, 162.2, 157.2, 145.2, 143.0, 129.2,
119.7, 114.2, 112.9, 110.4, 102.7, 55.8, 55.3.
4.2.3. 2-(p-Methoxyphenyl)benzoxazole (3ac). Obtained (2/98
ethyl acetate/hexane) as a white solid (220.74 mg, 98% yield);
mp 104.0–106.0 °C (lit.8b 103.0 °C); 1H NMR (300 MHz, CDCl3)
δ 8.18 (d, J = 9.0 Hz, 2H), 7.75–7.72 (m, 1H), 7.55–7.53 (m,
1H), 7.32–7.27 (m, 2H), 7.01 (d, J = 9.0 Hz, 2H), 3.88 (s, 3H);
13C NMR (75 MHz, CDCl3) δ 163.2, 162.4, 150.7, 142.3, 129.4,
124.6, 124.4, 119.7, 119.6, 114.3, 110.3, 55.3.
4.2.12.
5-Methoxy-2-(p-chlorophenyl)benzoxazole
(3de).
Obtained (2/98 ethyl acetate/hexane) as a white solid (244.10 mg,
94% yield); mp 137.0–139.0 °C (lit.17l 134.0–136.0 °C); 1H NMR
(300 MHz, CDCl3) δ 8.15 (d, J = 9.0 Hz, 2H), 7.50–7.43 (m, 3H),
7.25 (d, J = 6.0 Hz, 1H), 6.98–6.94 (m, 1H), 3.87 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 157.5, 145.3, 142.8, 137.6, 129.2,
128.6, 125.7, 113.9, 110.7, 102.8, 100.5, 55.9.
4.2.4. 2-(p-Chlorophenyl)benzoxazole (3ae). Obtained (1/99
ethyl acetate/hexane) as a white solid (206.70 mg, 90% yield);
mp 150.0–152.0 °C (lit.17a 148.0–150.0 °C); 1H NMR (400 MHz,
CDCl3) δ 8.22 (d, J = 8.0 Hz, 2H), 7.81–7.78 (m, 1H), 7.62–7.59
(m, 1H), 7.54–7.40 (m, 2H), 7.39–7.38 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 162.0, 150.7, 142.0, 137.7, 129.2, 128.8, 125.7,
125.3, 124.7, 120.1, 110.6.
4.2.13. 6-Fluoro-2-phenylbenzoxazole (3fa). Obtained (1/99
ethyl acetate/hexane) as a white solid (196.15 mg, 92% yield);
1
mp 109.0–111 °C (lit.17a 109.0–110.0 °C); H NMR (300 MHz,
CDCl3) δ 8.19 (t, J = 4.2 Hz, 3.3 Hz, 2H), 7.67 (dd, J = 5.1 Hz,
5.1 Hz, 1H), 7.51 (d, J = 3.9 Hz, 3H), 7.27 (t, J = 7.8 Hz, 6.6 Hz,
1H), 7.08 (t, J = 9.0 Hz, 9.0 Hz, 1H); 13C NMR (75 MHz, CDCl3)
δ 163.6, 162.2, 159.0, 150.7, 150.5, 138.3, 131.5, 128.9, 128.5,
127.4, 126.8, 120.2, 120.1, 112.6, 112.3, 98.8, 98.4. 19F NMR
(CDCl3, 470.6 MHz) δ -114.945 (dd, J = 11.5 Hz, 7.5 Hz).
4.2.5. 5-Methyl-2-phenylbenzoxazole (3ba). Obtained (1/99 ethyl
acetate/hexane) as a white solid (205.06 mg, 98% yield); mp
1
104.0–106.0 °C (lit.8b 108.0 °C); H NMR (300 MHz, CDCl3) δ

6
Tetrahedron
ACCEPTED MANUSCRIPT
4.2.14.
5,7-Dichloro-6-methyl-2-phenylbenzoxazole
(3ja).
(282.43 mg, 90% yield); mp 112.0–114.0 °C; 1H NMR (500
Obtained (1/99 ethyl acetate/hexane) as a white solid (242.00 mg,
87% yield); mp 117.0–119.0 °C; H NMR (300 MHz, CDCl3) δ
MHz, CDCl3) δ 8.11 (d, J = 1.5 Hz, 1H), 8.02 (dd, J = 2.0 Hz, 1.5
Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.75–7.73 (m, 1H). 7.47–7.35
(m, 2H), 7.34–7.33 (m, 1H); 13C NMR (125 MHz, CDCl3) δ
167.5, 153.6, 134.4, 134.2, 134.1, 132.4, 132.2, 131.6, 127.7,
126.1, 123.4, 122.2, 122.1.
1
8.21 (dd, J = 3.0 Hz, 3.0 Hz, 2H), 7.65 (s, 1H), 7.53–7.51 (m,
3H), 2.55 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.0, 146.8,
140.9, 132.1, 131.3, 131.1, 129.0, 127.8, 126.3, 118.5, 116.4,
17.0. HRMS (EI) calcd for C14H10Cl2NO 278.0134 [M+H]+;
found 278.0136.
4.2.23. 5-Chloro-2-methylbenzothiazole (4kk). Obtained (1/99
ethyl acetate/hexane) as a off white solid (168.97 mg, 92%
1
4.2.15.
5,7-Dichloro-6-methyl-2-(p-chlorophenyl)benzoxazole
yield); mp 70.0–72.0 °C (lit.10b 68.0–69.0 °C); H NMR (500
(3je). Obtained (1/99 ethyl acetate/hexane) as a white solid
(265.70 mg, 85% yield); mp 182.0–184.0 °C; 1H NMR (300
MHz, CDCl3) δ 8.17 (d, J = 9.0 Hz, 2H), 7.67 (s, 1H), 7.50 (d, J
= 9.0 Hz, 2H), 2.57 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 157.3,
148.2, 139.6, 136.7, 132.4, 129.6, 129.2, 128.8, 128.6, 127.4,
127.1, 126.2, 118.9. HRMS (ESI+) calcd for C14H9Cl3NO
311.9744 [M+H]+; found 311.9746.
MHz, CDCl3) δ 7.92 (s, 1H), 7.72 (d, J = 5.0 Hz, 1H), 7.32 (d, J
= 5.0 Hz, 1H), 2.83 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
169.0, 154.3, 134.0, 132.0, 125.3, 122.4, 122.1, 20.3.
4.2.24. 2-(Thienyl)benzoxazole (3ai). Obtained (1/99 ethyl
acetate/hexane) as a white solid (173.07 mg, 86% yield); mp
80.0–82.0 °C (lit.8b 81.0–82.0 °C); 1H NMR (300 MHz, CDCl3) δ
7.83 (d, J = 3.0 Hz, 1H), 7.67–7.64 (m, 1H), 7.48–7.45 (m, 2H),
7.28–7.24 (m, 2H), 7.10 (dd, J = 3.0 Hz, 6.0 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 159.1, 150.5, 142.0, 130.3, 130.0, 129.7,
128.3, 125.1, 124.7, 119.8, 110.4.
4.2.16. 2-(Naphthalen-2-yl)benzoxazole (3ag). Obtained (1/99
ethyl acetate/hexane) as a white solid (218.30 mg, 89% yield);
1
mp 114.0–115.0 °C (lit.9i 113.0–115.0 °C); H NMR (300 MHz,
CDCl3) δ 8.79–8.75 (m, 1H), 8.34–8.27 (m, 1H), 8.00–7.80 (m,
4H), 7.64–7.54 (m, 2H), 7.40–7.35 (m, 2H), 7.26 (s, 1H); 13C
NMR (125 MHz, CDCl3) δ 163.4, 151.0, 142.4, 134.9, 133.2,
129.1, 128.9, 128.3, 128.1, 128.0, 127.1, 125.3, 124.8, 124.6,
124.1, 120.2, 110.8.
4.2.25. 5-Methyl-2-(thienyl)benzoxazole (3bi). Obtained (2/98
ethyl acetate/hexane) as a white solid (187.30 mg, 87% yield);
mp 82.0–84.0 °C (lit.4d 81.0–82.0 °C); 1H NMR (300 MHz,
CDCl3) δ 7.81 (d, J = 3.0 Hz, 1H), 7.46 (d, J = 3.0 Hz, 1H), 7.43
(s, 1H), 7.33 (d, J = 9.0 Hz, 1H), 7.18–7.05 (m, 2H), 2.40 (s, 3H).
4.2.17. 5-Methyl-2-(naphthalene-2-yl)benzoxazole (3bg).17m
4.2.26. 5-Chloro-2-(thienyl)benzoxazole (3ei). Obtained (2/98
Obtained (1/99 ethyl acetate/hexane) as a white solid (236.00 mg,
ethyl acetate/hexane) as a white solid (200.35 mg, 85% yield);
1
91% yield); mp 155.0–157.0 °C; H NMR (300 MHz, CDCl3) δ
1
mp 120.0–122.0 °C (lit.8o 120.0–121.0 °C); H NMR (300 MHz,
8.77 (s, 1H), 8.30 (d, J = 9.0 Hz, 1H), 7.93 (dd, J = 6.0 Hz, 9.0
Hz, 3H), 7.59–7.48 (m, 4H), 7.18 (d, J = 9.0 Hz, 2H), 2.51 (s,
3H).
CDCl3) δ 7.89 (d, J = 3.0 Hz, 1H), 7.68 (s, 1H), 7.58 (d, J = 3.0
Hz, 1H), 7.45 (d, J = 9.0 Hz, 1H), 7.29 (d, J = 9.0 Hz, 1H), 7.20–
7.17 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 160.4, 149.1, 143.2,
130.9, 130.5, 130.2, 129.1, 128.4, 125.3, 119.7, 111.1.
4.2.18. 2-(Biphenyl-1-yl)benzoxazole (3ah). Obtained (1/99 ethyl
acetate/hexane) as a white solid (244.20 mg, 90% yield); mp
4.2.27. 2-(Furyl)benzoxazole (3aj). Obtained (1/99 ethyl
acetate/hexane) as a white solid (157.41 mg, 85% yield); mp
84.0–86.0 °C (lit.8b 83.0–85.0 °C); 1H NMR (300 MHz, CDCl3) δ
7.65 (dd, J = 3.0 Hz, 3.0 Hz, 1H), 7.67 (d, J = 3.0 Hz, 1H), 7.58–
7.55 (m, 1H), 7.35 (dd, J = 3.0 Hz, 3.0 Hz, 2H), 7.28 (d, J = 3.0
Hz, 1H), 6.62 (d, J = 3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ
150.2, 145.8, 141.7, 125.3, 124.9, 124.4, 120.1, 118.8, 114.3,
112.2, 110.5.
1
143.0–144.0 °C (lit.17h 142.6–143.8 °C); H NMR (300 MHz,
CDCl3) δ 8.33 (d, J = 9.0 Hz, 2H), 7.81–7.75 (m, 3H), 7.67 (dd, J
= 3.0 Hz, 3.0 Hz, 2H), 7.60 (dd, J = 3.0 Hz, 3.0 Hz, 1H), 7.51–
7.46 (m, 2H), 7.43–7.40 (m, 1H), 7.36 (dd, J = 3.0 Hz, 3.0 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 162.8, 150.7, 144.1, 142.1,
139.9, 128.8, 128.057, 128.016, 127.4, 127.1, 125.9, 125.0,
124.5, 119.9, 110.5.
4.2.19. 5-Chloro-2-methylbenzoxazole (3ek). Obtained (1/99
4.2.28. 5-Methyl-2-(furyl)benzoxazole (3bj). Obtained (1/99 ethyl
acetate/hexane) as a white solid (173.31 mg, 87% yield); mp
52.0–54.0 °C (lit.4d 52.0–53.0 °C); 1H NMR (300 MHz, CDCl3) δ
7.66 (s, 1H), 7.54 (s, 1H), 7.42 (d, J = 9.0 Hz, 1H), 7.17 (dd, J =
15.0 Hz, 9.0 Hz, 2H), 6.60 (d, J = 3.0 Hz, 1H), 2.48 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 155.6, 148.6, 145.7, 142.9, 142.0,
134.9, 126.6, 120.2, 114.2, 112.4, 110.1, 100.0, 21.7.
ethyl acetate/hexane) as a off white solid (137.43 mg, 82%
1
yield); mp 60.0–62.0 °C (lit.10a 61.0–64.0 °C); H NMR (300
MHz, CDCl3) δ 7.54 (s, 1H), 7.23 (dd, J = 8.4 Hz, 8.1 Hz, 2H),
2.55 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 165.0, 149.1, 142.2,
129.0, 124.3, 118.9, 110.6, 14.1.
4.2.20. 5-Chloro-2-phenylbenzothiazole (4ka). Obtained (1/99
ethyl acetate/hexane) as a light yellow powder (226.07 mg, 92%
yield); mp 141.0–143.0 °C (lit.17n 139.0–141.0 °C); 1H NMR
(500 MHz, CDCl3) δ 8.05–8.02 (m, 3H), 7.75 (d, J = 10 Hz, 1H),
4.2.29. 5-Methoxy-2-(furyl)benzoxazole (3dj). Obtained (1/99
ethyl acetate/hexane) as a white solid (202.30 mg, 94% yield);
1
mp 70.0–72.0 °C; H NMR (300 MHz, CDCl3) δ 7.66 (s, 1H),
7.48 (d, J = 5 Hz, 2H), 7.46 (s, 1H), 7.32 (d, J = 10 Hz, 1H); 13
C
7.43 (d, J = 9.0 Hz, 1H), 7.24 (dd, J = 3.0 Hz, 6.0 Hz, 2H), 6.94
(d, J = 12.0 Hz, 1H), 6.60 (s, 1H), 3.86 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 157.7, 145.6, 144.8, 142.8, 142.6, 114.0, 113.8,
112.2, 110.6, 103.0, 55.90. HRMS (ESI+) calcd for C12H10NO3
216.0655 [M+H]+; found 216.0667.
NMR (125 MHz, CDCl3) δ 169.9, 155.0, 133.4, 133.3, 132.4,
131.4, 129.1, 127.7, 125.7, 123.1, 122.3.
4.2.21.
5-Chloro-2-(4-(trifluoromethyl)phenyl)benzothiazole
(4kd). Obtained (1/99 ethyl acetate/hexane) as a light yellow
powder (282.36 mg, 87% yield); mp 125.0–127.0 °C (lit.17o
4.2.30. 5-Chloro-2-(furyl)benzoxazole (3ej). Obtained (1/99 ethyl
acetate/hexane) as a white solid (186.68 mg, 85% yield); mp
80.0–82.0 °C (lit.11b 78.0–79.0 °C); 1H NMR (300 MHz, CDCl3)
δ 7.73–7.53 (m, 2H), 7.45–7.22 (m, 3H), 6.57 (dd, J = 3.0 Hz, 3.0
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 161.5, 151.6, 149.9,
147.4, 144.7, 142.4, 141.1, 130.2, 130.0, 125.5, 124.2, 120.0,
118.8, 117.8, 112.9, 112.2, 112.1, 111.4, 110.8.
1
123.0–128.0 °C); H NMR (500 MHz, CDCl3) δ 8.18 (d, J = 5
Hz, 2H), 8.07 (s, 1H), 7.82 (s, J = 10 Hz, 1H), 7.75 (d, J = 10 Hz,
2H), 7.39 (d, J = 5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ
168.0, 155.0, 136.5, 133.5, 133.1, 132.8, 132.8, 127.9, 126.4,
126.2, 123.5, 122.5.
4.2.22.
2-(2-Bromophenyl)-5-chlorobenzothiazole
(4kf).17o
Obtained (1/99 ethyl acetate/hexane) as a light yellow powder

7
4.2.31. 5-Chloro-2-(furyl)benzothiazole (4kj). Obtained (1/99
ethyl acetate/hexane) as a yellow powder (212.12 mg, 90%
yield); mp 114.0–116.0 °C (lit.17p 113.0–115.0 °C); 1H NMR
(500 MHz, CDCl3) δ 8.01 (d, J = 5.0 Hz, 1H), 7.78 (d, J = 10 Hz,
1H), 7.61 (s, 1H), 7.34 (dd, J = 5.0 Hz, 10 Hz, 1H), 7.20 (d, J =
5.0 Hz, 1H), 6.60 (d, J = 5.0 Hz, 1H); 13C NMR (125 MHz,
CDCl3) δ 159.3, 154.7, 148.5, 145.1, 132.6, 125.7, 122.9, 122.3,
112.7, 112.0.
7.24 (d, J = 9.0 Hz, 1H), 7.19 (s, 1H); 13C NMR (75 MHz,
ACCEPTED MANUSCRIPT
CDCl3) δ 163.6, 148.5, 142.4, 131.1, 129.2, 128.1, 126.9, 125.9,
124.5, 119.1, 110.4, 28.7 (grease).
4.2.40. 5-Chloro-2-(p-tolyl)benzoxazole (3eb). Obtained (1/99
ethyl acetate/hexane) as a white solid (212.01 mg, 87% yield);
mp 140.0–142.0 °C (lit.8b 138.8–140.0); H NMR (300 MHz,
1
CDCl3) δ 8.12 (d, J = 9.0 Hz, 2H), 7.72 (s, 1H), 7.48 (d, J = 9.0
Hz, 1H), 7.33 (d, J = 9.0 Hz, 2H), 7.29 (s, 1H), 2.45 (s, 3H).
4.2.32. 5-Carboxylicacid-2-phenylbenzoxazole (3ga).17e Obtained
4.2.41.
5-Chloro-2-(p-methoxyphenyl)benzoxazole
(3ec).
(10/90 ethyl acetate/hexane) as a white solid (222.50 mg, 93%
Obtained (1/99 ethyl acetate/hexane) as a white solid (231.12 mg,
1
yield); mp 242.0–243.0 °C; H NMR (300 MHz, CDCl3) δ 8.47
89% yield); mp 144.0–146.0 °C (lit.8b 146.0 °C); H NMR (300
1
(s, 1H), 8.27 (d, J = 6.0 Hz, 2H), 8.13 (d. J = 6.0Hz, 1H), 7.64–
7.55 (m, 4H), 5.34 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 167.8,
163.9, 153.3, 141.8, 131.6, 128.7, 127.7, 127.4, 127.0, 126.3,
121.8, 109.9.
MHz, CDCl3) δ 8.14 (d, J = 9.0 Hz, 2H), 7.68 (s, 1H), 7.43 (d, J
= 9.0 Hz, 1H), 7.25 (d, J = 9.0 Hz, 1H), 7.00 (d, J = 9.0 Hz, 2H),
3.88 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.5, 162.7, 149.3,
143.5, 129.8, 129.5, 124.7, 119.5, 119.1, 114.4, 111.0, 55.4.
4.2.33. 5-Carboxylicacid-2-(p-methoxyphenyl)benzoxazole (3gc).
Obtained (10/90 ethyl acetate/hexane) as a white solid (255.80
mg, 95% yield); mp 245.0–247.0 °C; 1H NMR (300 MHz,
DMSO-d6) δ 13.08 (s, 1H), 8.31–8.21 (m, 3H), 8.06 (d, J = 8.4
Hz, 1H), 7.89 (d, J = 6.0 Hz, 1H), 7.24–7.15 (m, 2H), 3.94 (s,
3H); 13C NMR (75 MHz, DMSO-d6) δ 167.0, 163.9, 162.6,
153.0, 141.9, 129.5, 127.8, 126.6, 120.6, 118.3, 114.9, 110.7,
55.5. HRMS (ESI+) calcd for C15H12NO4 270.0761 [M+H]+;
found 270.0762.
4.2.42. 5-Chloro-2-(p-trifluoromethylphenyl)benzoxazole (3ed).
17h Obtained (3/97 ethyl acetate/hexane) as a yellow solid (238.13
1
mg, 80% yield); H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 7.2
Hz, 2H), 7.69–7.56 (m, 3H), 7.41 (t, J = 4.5 Hz, 8.7 Hz, 1H),
7.27 (d, J = 2.1 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 165.9,
147.2, 140.7, 134.3, 131.7, 131.0, 130.3, 130.1, 129.9, 128.2,
127.3, 126.8, 126.7, 125.6, 124.6, 120.1, 118.0, 111.4, 111.0,
88.3. 19F NMR (CDCl3, 470.6 MHz) δ -62.914 (d, J = 31.5 Hz).
4.2.43.
5-Chloro-2-(p-chlorophenyl)benzoxazole
(3ee).
4.2.34. 5-Nitro-2-phenylbenzoxazole (3ha). Obtained (7/93 ethyl
Obtained (1/99 ethyl acetate/hexane) as a white solid (224.50 mg,
85% yield); mp 193.0–195.0 °C (lit.17h 192.8–194.9 °C); 1H
NMR (300 MHz, CDCl3) δ 8.12 (d, J = 9.0 Hz, 2H), 7.71 (d, J =
3.0 Hz, 1H), 7.47 (d, J = 9.0 Hz, 1H), 7.36–7.28 (m, 3H); 13C
NMR (75 MHz, CDCl3) δ 164.1, 149.2, 144.3, 143.3, 129.9,
129.3, 128.8, 127.9, 127.2, 125.6, 125.1, 124.4, 122.7, 119.7,
117.9, 111.1, 110.8, 14.9.
acetate/hexane) as a white solid (199.40 mg, 83% yield); mp
1
174.0–176.0 °C (lit.17f 171.5–172.5 °C); H NMR (300 MHz,
CDCl3) δ 8.66 (d, J = 9.0 Hz, 1H), 8.36–8.26 (m, 3H), 7.68 (d, J
= 9.0 Hz, 1H), 7.62–7.54 (m, 3H); 13C NMR (75 MHz, CDCl3) δ
166.0, 154.3, 145.5, 142.6, 132.6, 129.1, 128.0, 126.0, 121.1,
116.2, 110.7.
4.2.35. 5-Nitro-2-(p-methoxyphenyl)benzoxazole (3hc). Obtained
(7/93 ethyl acetate/hexane) as a white solid (235.11 mg, 87%
yield); mp 185.0–187.0 °C (lit.17j 184.0–186.0 °C); 1H NMR (300
MHz, CDCl3) δ 8.56 (d, J = 1.8 Hz, 1H), 8.27–8.16 (m, 3H), 7.61
(d, J = 8.7 Hz, 1H), 7.03 (d, J = 8.7 Hz, 2H), 3.90 (s, 3H); 13C
NMR (75 MHz, CDCl3): δ 166.0, 163.1, 154.2, 145.3, 142.8,
129.9, 120.6, 118.3, 115.7, 114.5, 110.3, 55.5.
4.2.44. 5-Bromo-2-(p-methoxyphenyl)benzimidazole (5ll).
Obtained (15/85 ethyl acetate/hexane) as an off yellow solid
(139.50 mg, 46% yield); mp 192.0–194.0 °C; 1H NMR (500
MHz, CD3OD) δ 7.96–7.93 (m, 2H), 7.65 (d, J = 2.0 Hz, 1H),
7.42 (d, J = 8.5 Hz, 1H), 7.29 (dd, J = 8.5 Hz, 2.0 Hz, 1H), 7.02
(dd, J = 9.0 Hz, 2.0 Hz), 4.89 (br, 1H), 3.82 (s, 3H); 13C (125
MHz, CD3OD) δ 163.2, 154.6, 129.4, 126.6, 122.8, 118.4, 116.3,
115.5, 55.9; HRMS (ESI+) calcd for C14H12BrN2O 303.0128
[M+H]+; found 303.0135.
4.2.36. 5-Nitro-2-(p-chlorophenyl)benzoxazole (3he). Obtained
(7/93 ethyl acetate/hexane) as a white solid (219.40 mg, 80%
1
yield); mp 220.0–222.0 °C (lit.8a 219.0 °C); H NMR (300 MHz,
CDCl3) δ 8.64 (s, 1H), 8.34 (d, J = 9.0 Hz, 1H), 8.21 (d, J = 9.0
Hz, 2H), 7.68 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 9.0 Hz, 2H).
Acknowledgments
We gratefully acknowledge the generous financial support
from the Science and Engineering Research Board (Grant No.
SB/S1/OC-30/2013) and the Council of Scientific and Industrial
Research (Grant No. 02(0072)/12/EMR-II), New Delhi. The
authors (A.S. & G.S.) are thankful to CSIR, New Delhi for senior
research fellowships.
4.2.37. 5-Carbonitrile-2-phenylbenzoxazole (3ia). Obtained
(30/70 ethyl acetate/hexane) as a white solid (185.00 mg, 84%
yield); mp 188.0–190.0 °C (lit.17g 189.0–190.0 °C); 1H NMR
(300 MHz, CDCl3) δ 8.25 (d, J = 6.0 Hz, 2H), 8.07 (s, 1H), 7.65
(d, J = 3.0 Hz, 2H), 7.61 (d, J = 9.0 Hz, 1H), 7.56 (d, J = 9.0 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 165.2, 153.2, 142.6, 132.5,
129.1, 128.0, 126.0, 124.6, 118.7, 111.8, 108.6.
Supplementary material
4.2.38. 5-Carbonitrile-2-(p-methoxyphenyl)benzoxazole (3ic).
Obtained (30/70 ethyl acetate/hexane) as a white solid (215.22
mg, 86% yield); mp 154.0–156.0 °C; 1H NMR (300 MHz,
DMSO-d6) δ 8.32 (s, 1H), 8.17–8.14 (m, 2H), 7.96 (d, J = 6.0 Hz,
1H), 7.84 (d, J = 6.0 Hz, 1H), 7.17 (d, J = 9.0 Hz, 2H), 3.87 (s,
3H); 13C NMR (75 MHz, DMSO-d6) δ 168.3, 166.1, 152.7,
142.1, 129.6, 129.2, 123.9, 118.8, 114.9, 112.2, 55.5. HRMS
(ESI+) calcd for C15H11N2O2 251.0815 [M+H]+; found 251.0829.
Supplementary data (1H, 13C and 19F NMR spectra of
compounds) associated with this article can be found in the
online version, at http://dx.doi.org/
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