Divergent strategy for the chemoselective synthesis of N-Arylbenzimidazoles and N-Arylindazoles from arylamino oximes

Article abstract of DOI:10.1016/j.tet.2020.130945

An efficient and divergent synthesis of N-arylbenzimidazoles and N-arylindazoles from arylamino oximes based on reaction conditions selection was developed. The synthesis was approached by treating oximes with BTC and the chemoselectivity was regulated by the amount of Et₃N. This switchable N–N and N–C bond formation process features mild reaction conditions, simple execution, high chemoselectivity and broad substrate scope.

Full text of DOI:10.1016/j.tet.2020.130945

Journal Pre-proof
Divergent strategy for the chemoselective synthesis of N-Arylbenzimidazoles and N-
Arylindazoles from arylamino oximes
Zhen-Hua Li, Xiao-Meng Sun, Jin-Jing Qin, Zhi-Yong Tan, Wen-Biao Wang, Yao Ma
PII:
S0040-4020(20)30035-1
https://doi.org/10.1016/j.tet.2020.130945
TET 130945
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 November 2019
Revised Date: 18 December 2019
Accepted Date: 7 January 2020
Please cite this article as: Li Z-H, Sun X-M, Qin J-J, Tan Z-Y, Wang W-B, Ma Y, Divergent strategy for
the chemoselective synthesis of N-Arylbenzimidazoles and N-Arylindazoles from arylamino oximes,
Tetrahedron (2020), doi: https://doi.org/10.1016/j.tet.2020.130945.
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Graphic Abstract

Divergent Strategy for the Chemoselective Synthesis of
N-Arylbenzimidazoles and N-Arylindazoles from Arylamino Oximes
Zhen-Hua Li*, Xiao-Meng Sun, Jin-Jing Qin, Zhi-Yong Tan, Wen-Biao Wang, Yao Ma
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education,
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, People’s
Republic of China
E-mail: lizhenhua@zjut.edu.cn
1

Abstract
An efficient and divergent synthesis of N-arylbenzimidazoles and N-arylindazoles from arylamino oximes based on
reaction conditions selection was developed. The synthesis was approached by treating oximes with BTC and the
chemoselectivity was regulated by the amount of Et3N. This switchable N−N and N−C bond formation process
features mild reaction conditions, simple execution, high chemoselectivity and broad substrate scope.
Keywords: Divergent synthesis, Chemoselectivity, N-arylbenzimidazoles, N-arylindazoles,
Bis(trichloromethyl)carbonate
2

1. Introduction
The isomeric N-arylbenzimidazoles and N-arylindazoles are ubiquitous in the realms of pharmacologically
active agents and natural products.1 For instance, molecules based on N-arylbenzimidazoles have attracted
extensive attention due to their numerous pharmaceutically activities, including antifungal drugs,2 NIMA-related
kinase2 (Nek2) inhibitors, lymphocyte specific kinase (Lck) inhibitors, GABAA receptor agonists and the hepatitis
C virus (HCV) NS5B polymerase inhibitors (Figure 1).1a,3 N-arylbenzimidazoles have also been used as the
backbone in dyes, polymers and ligands.4 N-arylindazoles, the isomer of N-arylbenzimidazoles, also exhibited a
broad spectrum of bioactivities, including heat shock protein 90 (HSP90) inhibitors, NF-κB inducing kinase (NIK)
inhibitors, selective GPR120 agonists (Figure 1).5 Given the importance of the class of heterocycles as biologically
active substances has continued to inspire the pursuit of their general and efficient synthesis.
Figure 1. N-arylbenzimidazoles and indazoles as medicinal agents and biologically active compound
s
Generally, N-arylbenzimidazoles were prepared through the condensation of ortho-substituted aniline
derivatives with carbonyls under oxidative conditions or metal catalysis,6 benzylamines7 and benzylalcohols8 were
also employed as the substrates instead of the carbonyls. As an alternative, intramolecular cyclization of amidines is
a straightforward method for the synthesis of N-arylbenzimidazole moiety (Scheme 1, a).9 On the other hand, the
synthetic methods of N-arylindazoles included (i) condensations of aryl hydrazines with ortho-halobenzoyl
derivatives,10 (ii) the 1,3-dipolar cycloadditions of benzynes with diazo compounds or aryl hydrazines,11 (iii)
intramolecular cyclizations of hydrazones,12 N−H ketimines,13 oximes and oxime derivatives (Scheme 1, b).14
3

Scheme 1 Synthesis of N-arylbenzimidazole or N-Arylindazoles via intramolecular cyclizations
Especially, oximes were a class of essential compounds in organic synthesis,15 due to their easy preparation,
efficient reactivity and harmless byproducts. Generally, they were widely employed in the construction of nitriles
and amides.16 Besides, they provided convenient methods to prepare functionalized N-containing heterocycles via
SN2 reaction,17 radical cyclization,18 and other routes.19 In 2010, Stambuli and co-workers reported a method for the
selectively produce N-arylindazoles and benzimidazoles from common arylamino oximes by using
methanesulfonyl chloride and different base.14a Despite the advance, this processes still suffered some limitations,
such as corrosive reagent, tedious procedures, limited in the substrate range. Thus, development of an operationally
simple, tunable synthetic method for N-substituted benzimidazoles and indazoles from the same substrate has
remained a challenging task.
Bis(trichloromethyl)carbonate (BTC), also known as triphosgene or solid phosgene, has been considered as an
easily handled alternative to highly toxic phosgene.20 The reagent has been used in various situations, including
chlorination, acylation, rearrangement and cyclization, etc.21 As part of our ongoing research in developing the
BTC system to synthesize biologically relevant heterocyclic compounds,21d,22 we demonstrated herein an efficient
protocol for the divergent synthesis of N-arylbenzimidazoles and N-arylindazoles from arylamino oximes mediated
by BTC controlled by Et3N with more substrate scope and providing moderate to excellent yields.
2. Results and Disscussion
Initially, we commenced our investigation by the model reaction of N-phenyl o-amino acetophenone oxime
4

(2a) with BTC/TPPO14d,22a which gave compounds 3a and 4a in 15% and 20% yields, respectively (Table 1, entry
1). Subsequently, we investigated different BTC systems in order to afford compound 3a with a higher yield. The
BTC/DMF system (Vilsmeier reagent 21e
could not afford the desired result (Table 1, entry 2). To our delight, the
)
N-Arylbenzimidazole 3a was obtained in 73% yield with high chemoselectivity only mediated by BTC (Table 1,
entry 3). Next, the yield of 3a reached 88% when the molar ratio of 2a: BTC was tuned to 1: 0.4 (Table 1, entries
4-6). The solvents and reaction temperature were also investigated (Table 1 entries 7-8),23 the yield of 3a improved
to 94% with the optimal reaction conditions (Table 1, entry 8). Encouraged by the above results and with the
optimal conditions of the N-arylbenzimidazole synthesis in hand, we turned our attention to select the appropriate
reaction conditions which favor the formation of N-arylindazoles. Considering that Beckmann rearrangement (BR)
reactions commonly catalyzed by acids, we explored whether the BR progress could be inhibited by the addition of
bases.14a In further experimental research, we found that base and low temperature could favor the formation of
N-arylindazoles 4a. After investigated temperature, solvents and the molar ratio of 2a: BTC: Et3N, the yield of 4a
could reach 89% in DCM at -5 °C when the molar equivalent ratio of 2a: BTC: Et3N was 1: 0.75: 6 (Table 1,
entries 9-14). Screening of other bases such as pyridine, DIPEA, DBU, DMAP, DABCO, Na2CO3 showed that
Et3N was the appropriate base for this reaction (Table 1, entries 15-20).
Table 1 Optimization of the reaction conditionsa,b
entry
BTC system
BTC (eq.)c
Base (eq.)c
Solvent
T (oC)
3a Yield (%)d
4a Yield (%)d
1
BTC/TPPOe
BTC/DMFf
BTC
0.33
0.33
0.33
0.35
0.4
/
DCE
DCE
DCE
DCE
DCE
DCE
DCM
PhCl
DCM
DCM
25
25
25
25
25
25
25
25
25
25
15
18
73
75
88
88
85
94
30
27
20
16
2
/
3
/
trace
trace
trace
trace
trace
trace
65
4
BTC
/
5
BTC
/
6
BTC
0.5
/
7
BTC
0.4
/
/
8
BTC
0.4
9
BTC
0.5
Et3N (5.5)
Et3N
10
BTC
0.5
67
5

11
12
13
14
15
16
17
18
19
20
BTC
BTC
BTC
BTC
BTC
BTC
BTC
BTC
BTC
BTC
0.75
1
Et3N
Et3N
DCM
DCM
PhCl
-5
-10
-10
-5
trace
trace
32
89
87
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
Et3N
70
Et3N (7)
Pyridine
DIPEA
DBU
DCM
DCM
DCM
DCM
DCM
DCM
DCM
trace
45
84
-5
trace
trace
trace
0
-5
50
-5
55
DMAP
DABCO
Na2CO3
-5
0
-5
46
trace
-5
34
30
b
aUnless otherwise specified, the reaction conditions: 2a (0.5 mmol, 1eq.), BTC (x mmol, x eq.), base (3 mmol, 6 eq.) and solvent (8 or 10 ml), 3h.
d
e
BTC is short for bis(trichloromethyl)carbonate, TPPO is short for triphenylphosphine oxide. cmolar equivalent ratio Isolated yields based on 2a. the
molar equivalent ratio of BTC:TPPO =1: 3. fthe molar equivalent ratio of BTC:DMF=1: 3
Table 2 Synthesis of N-arylbenzimidazole 3 from oxime 2a, b
aReaction conditions A: 2 (0.5 mmol, 1 eq.), BTC (0.2 mmol, 0.4 eq.), PhCl (8 ml), 25 °C for 3 h. bIsolated yield based on compound 2.
Subsequent work was to investigate the substrate scopes of this method to synthesize N-arylbenzimidazoles 3
under the optimized conditions (Table 2). Satisfactorily, the substituents on the N-substituted arenes had no
significant effect on the reaction and afforded the products in good to excellent yields of 74% to 94% including
：

electron-withdrawing or electron-donating groups (Table 2, 3a-3m). Among them, the yields of 3f and 3g decreased
slightly. The lower yields might be caused by electron-withdrawing groups reduced the nucleophilic ability of the
amino group. The R2 groups including aryl or aliphatic groups on oximes 2 also worked well resulting in a slight
decrease in yields due to steric hindrance but still affording the products in good yields of 82% to 89% (Table 2,
3n-3s).
Unfortunately,
the
reaction
results
of
N-benzyl-o-aminoacetophenone
oxime
and
N-methyl-o-aminoacetophenone oxime were complicated and did not afford the products, which indicated that the
alkyl group and benzyl group might not be suitable for this position in this method.
Table 3 Synthesis of N-Arylindazoles 4 from oxime 2a, b
aReaction conditions B: 2 (0.5 mmol, 1 eq.), BTC (0.375 mmol, 0.75 eq.), Et3N (3 mmol, 6 eq.), DCM (10 ml) at -5 °C for 3 h. bIsolated yield based on
2.
Next, we investigated the selective formation of N-arylindazoles 4 using the optimized condition (Table 3).
Medium yields were obtained for the substrates that contained arenes with electron-donating groups at the para,
meta or ortho positions (Table 3, 4a-4c, 4h, 4k). However, lower yields of indazoles were obtained with the
7

N-substituted arenes including electron-withdrawing substituents (Table 3, 4d-4g, 4i-4j, 4l-4m), this might be
caused by the electronics of the group attached to the arene. When the R2 groups were aryl or aliphatic groups on
oximes 2, the yields decreased slightly due to steric hindrance (Table 3, 4n-4s). Interestingly,
N-benzyl-o-aminoacetophenone oxime (Table 3, 2t-2v) afforded the corresponding products with moderate yields
of 70%, 76% and 65%, respectively. However, N-methyl-o-aminoacetophenone oxime still failed in the tests.
In order to demonstrate the utility of this method, several larger scale reactions were conducted, as shown in
scheme 2. To our delight, the method exhibited good stability. When the oxime 2d was magnified to 10 mmol (2.60
g), the product 3d still afforded in 2.14 g, 88% isolated yield (Scheme 2a). And the oxime 2a was magnified to 10
mmol (2.26 g), the product 4a afforded in 1.77 g, 85% isolated yield (Scheme 2b).
Scheme 2 Larger Scale Reaction
The inconsonant experimental results of N-alkyl-o-aminoacetophenone oxime (2t-2v) and
N-aryls-o-aminoacetophenone oxime (2a-2s) have attracted our attention. Generally, the nucleophilicity of N-alkyl
motifs is stronger than N-aryls according to the delocalization of electrons in the N-aryls structure. We speculate
that the difference nucleophilicity of amino between N-alkyl-o-aminoacetophenone oxime (2t-2v) and
N-aryls-o-aminoacetophenone oxime (2a-2s) led to different experimental results. The experiments (a) was
8

performed under condition A, the results were complicated and compound 6 was detected. These results indicated
that due to the stronger nucleophilicity of N-alkyl motifs, the N-alkyl-o-aminoacetophenone oxime may reacted
with BTC, which resulted in no target product generation in standard condition A (Scheme 3, a). In order to get an
insight view into the reaction mechanism, several control experiments were conducted (Scheme 3). First, a
competitive experiment (b) was carried out under both reaction conditions A and B. Oxime 7 could be converted
into product 9 in 79% and 76% yields, respectively, while the compound 8 was not reacted with BTC and
compound 10 was not detected. This result indicated that the reactivity of N-OH was higher than the secondary
amine group. Next, the experiments (c) were performed under reaction conditions A and B. The acetanilide 11 was
isolated in 56% via Beckmann rearrangement under the condition A, however 11 was not produced under condition
B (Scheme 3, c). These results indicated that the compound 9 derivatives might be an important intermediate for
the reaction and the Beckmann rearrangement could be inhibited with the presence of Et3N. Finally, we carried out
the template reaction under HCl atmosphere for 3h and 5h, the desired product 3a was isolated in 54% and 92%,
respectively. These results revealed that HCl partial inhibited the nucleophilicity of the amino group in the reaction
(Scheme 3, d).
9

Scheme 3 Control experiments
Based on the above results and the literature reports,14a,21d,24 a plausible reaction mechanism was proposed,
which was elucidated in Scheme 4 using 2a as a typical example. Initially, the oxime 2a reacted with BTC led to
intermediate I. Then, two pathways are possible for the following steps. In one case (path a), intermediate I reacted
with a small amount of HCl in the reaction system to form intermediate II. The hydrochloride decreased the
nucleophilicity of the secondary amino group and simultaneously promoted Beckmann rearrangement to form
intermediate IV. Finally, N-arylbenzimidazole 3a was obtained by an intramolecular aza-cyclization of
intermediate IV. On the other case (Path b), the addition of Et3N neutralized the HCl and inhibiting the Beckmann
rearrangement. In addition, the Et3N served as a nucleophilic promoter to the intermediate I,21b 21f
thereby enabling
,
a dominant intramolecular nucleophilic substitution reaction under Et3N condition afforded N-arylindazoles 4a.
10

Scheme 4 Proposed mechanism
3. Conclusion
In summary, an efficient and divergent synthesis of N-arylbenzimidazoles and N-arylindazoles has been
developed from arylamino oximes based on reaction conditions selection. Thus, a series of N-arylbenzimidazoles
were synthesized via sequential Beckmann rearrangement and intramolecular aza-cyclization under BTC
conditions. N-arylindazoles were obtained via intramolecular nucleophilic substitution reactions by the addition of
Et3N. This switchable N−N and N−C bond formation process features mild reaction conditions, simple execution,
high chemoselectivity and broad substrate scope. Further investigations on applying this methodology for
preparation of other heterocycles are underway in our lab.
4. Experimental
4.1 General Methods
Synthetic reagents were purchased from Aladdin and used without further purification unless otherwise
indicated. Caution! BTC will release phosgene in a moist environment, especially at elevated temperatures; it is
highly not recommended to add BTC over 80°C. Analytical TLC (thin-layer chromatography) was performed with
0.25 mm silica gel G with a 254 nm fluorescent indicator. Melting points (m.p.) were obtained on a digital melting
point apparatus and uncorrected. 1H, 13C and 19F NMR spectra were recorded on a Brüker (400 MHz & 101 MHz &
11

376 MHz) spectrometer. Spectra were referenced internally to the residual proton resonance in CDCl3, DMSO-d6 or
tetramethylsilane as the internal standard. Chemical shifts (δ) were reported as part per million (ppm) in δ scale
downfield from TMS. Infrared (IR) data were recorded as films on potassium bromide plates on a NICOLET iS50
FT-IR spectrometer. EI-MS were recorded on a ThermoFisher ITQ1100 Ion Trap Mass Spectrometer.
High-resolution mass spectra (HRMS) were obtained on a Brüker mass spectrometer (ESI). Purification of products
was accomplished by column chromatography on silica gel.
4.1.1 General Procedure for Aryl Amination
To a round-bottom flask equipped with a reflux condenser and a magnetic bar were added Aminoacetophenone
(5 mmol, 1 eq.), the corresponding halide (7.5 mmol, 1.5 eq.), K2CO3 (6.25 mmol, 1.25 eq.), and Cu (15 mol%)
were suspended in PhCl (8 mL) and heated to reflux for 24 h and then cooled to room temperature. Water (15 mL)
was added and the reaction was extracted with EtOAc (15 mL × 3). The combined organic phases were dried over
anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified via flash chromatography
(0-5% EtOAc/hexanes).
1a–1m were prepared using known literture protocol and in agreement with the reported data.14a
1
Phenyl(2-(p-tolylamino)phenyl)methanone (1n)ꢀyellow oil, (1.034 g, 71%). H NMR (400 MHz, DMSO-d6) δ
9.68 (s, 1H), 7.67–7.56 (m, 3H), 7.51 (t, J = 7.5 Hz, 2H), 7.45–7.37 (m, 2H), 7.24 (d, J = 8.4 Hz, 1H), 7.13 (t, J =
8.3 Hz, 4H), 6.77 (t, J = 7.5 Hz, 1H), 2.27 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 198.0, 147.0, 139.0, 137.8,
134.2, 133.9, 132.2, 131.6, 129.8, 129.0, 128.2, 121.5, 120.3, 117.1, 114.7, 20.4. HRMS (ESI) m/z [M + H]+ calcd
for C20H17NO 288.1383, found 288.1391.
1
(5-Methyl-2-(p-tolylamino)phenyl)(phenyl)methanone (1o)ꢀyellow oil, (1.170 g, 82%). H NMR (400 MHz,
DMSO-d6) δ 9.33 (s, 1H), 7.67–7.56 (m, 3H), 7.50 (t, J = 7.5 Hz, 2H), 7.28–7.18 (m, 3H), 7.08 (q, J = 8.3 Hz, 4H),
2.25 (s, 3H), 2.18 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 197.8, 144.2, 138.8, 138.6, 134.9, 133.2, 131.7,
131.3, 129.8, 129.0, 128.3, 126.3, 121.4, 120.4, 115.8, 20.3, 20.0. HRMS (ESI): calcd for C21H19NO [M + H]+
302.1539, found 302.1546.
1
(5-Chloro-2-(p-tolylamino)phenyl)(phenyl)methanone (1p): yellow oil, (0.917 g, 66%). H NMR (400 MHz,
DMSO-d6) δ 9.37 (s, 1H), 7.68–7.59 (m, 3H), 7.52 (t, J = 7.5 Hz, 2H), 7.42 (dd, J = 9.0, 2.5 Hz, 1H), 7.34 (d, J =
2.5 Hz, 1H), 7.21 (d, J = 9.0 Hz, 1H), 7.10 (q, J = 8.4 Hz, 4H), 2.26 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ
12

196.6, 145.4, 138.1, 137.8, 133.6, 132.4, 132.1, 132.05, 129.9, 129.0, 128.4, 122.3, 121.4, 120.5, 117.2, 20.4.
HRMS (ESI): calcd for C20H16ClNO [M + H]+ 322.0993, found 322.0984.
(4-Fluorophenyl)(2-(p-tolylamino)phenyl)methanone (1q): yellow oil, (1.210 g, 85%).1H NMR (400 MHz,
DMSO-d6) δ 9.47 (s, 1H), 7.72 (dd, J = 8.3, 5.7 Hz, 2H), 7.41 (t, J = 7.3 Hz, 2H), 7.32 (t, J = 8.8 Hz, 2H), 7.24 (d, J
= 8.6 Hz, 1H), 7.11 (q, J = 8.4 Hz, 4H), 6.80 (t, J = 7.5 Hz, 1H), 2.26 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ
197.0, 164.6 (d, J = 250.1 Hz), 147.1, 138.6, 135.8 (d, J = 2.7 Hz), 134.6, 134.0, 132.5, 132.37 (d, J = 9.1 Hz),
130.3, 121.7, 121.3, 117.9, 115.8 (d, J = 21.9 Hz), 115.6, 20.9, 19F NMR (376 MHz, DMSO-d6) δ -107.79 (m).
HRMS (ESI): calcd for C20H16FNO [M + H]+ 306.1289, found 306.1297.
1-(2-(p-Tolylamino)phenyl)propan-1-one (1r): dark yellow oil, (0.910 g, 81%). 1H NMR (400 MHz, DMSO-d6) δ
10.39 (s, 1H), 7.95 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.7 Hz, 1H), 7.21–7.09 (m, 5H), 6.76 (t, J = 7.5 Hz, 1H), 3.06 (q,
J = 7.2 Hz, 2H), 2.28 (s, 3H), 1.10 (t, J = 7.2 Hz, 3H), 13C NMR (101 MHz, DMSO-d6) δ 203.8, 147.0, 137.4,
134.4, 132.8, 131.9, 129.9, 122.4, 118.4, 116.7, 113.7, 32.0, 20.4, 8.6. HRMS (ESI): calcd for C16H17NO [M + H]+
240.1383, found 240.1397.
4.1.2 General Procedure for the Synthesis of Oximes
Method A. To a round-bottom flask equipped with a reflux condenser and a magnetic bar were added the
ketone (1 mmol, 1 eq.), hydroxylamine hydrochloride (3 mmol, 3 eq.) and NaOH (6 mmol, 6 eq.), H2O (3mL),
EtOH (10 mL). The reaction was allowed to stir at 75 °C until complete consumption of the starting material was
observed by TLC. The bulk of the ethanol was removed in vacuo and water was added. The crude product was
extracted with EtOAc (3 × 15 mL), dried over Na2SO4 and concentrated. The crude oxime was purified via flash
chromatography (0-20% EtOAc/hexanes).
Method B. To a round-bottom flask equipped with a reflux condenser and a magnetic bar were added the
ketone (1 mmol, 1 eq.), hydroxylamine hydrochloride (3 mmol, 3 eq.) and pyridine (11 mmol, 11 eq.) were added
to methanol (8 mL). The reaction was heated at reflux until complete consumption of the starting material was
observed by TLC. The reaction was concentrated in vacuo, dissolved in EtOAc (10 mL), washed twice with water
(2 × 20mL), dried over Na2SO4 and concentrated. The crude oxime was purified via flash chromatography (0-20%
EtOAc/hexanes).
2a – 2m were prepared using known literture protocol and in agreement with the reported data.14a
1
(E)-Phenyl(2-(p-tolylamino)phenyl)methanone oxime (2n): yellow oil, (0.330 g, 23%). H NMR (400 MHz,
13

DMSO-d6) δ 11.68 (s, 1H), 7.45–7.39 (m, 2H), 7.36–7.24 (m, 5H), 7.04 (d, J = 7.4 Hz, 1H), 7.01–6.92 (m, 3H),
6.86 (d, J = 8.2 Hz, 2H), 6.67 (s, 1H), 2.19 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 154.5, 141.6, 141.0, 136.4,
130.0, 129.5, 129.2, 128.9, 128.8, 128.2, 126.8, 124.6, 120.3, 117.9, 117.8, 20.2. HRMS (ESI): calcd for
C20H18N2O [M + H]+ 303.1492, found 303.1498.
(E)-(5-Methyl-2-(p-tolylamino)phenyl)(phenyl)methanone oxime (2o): yellow oil, (0.370 g, 30%). 1H NMR (400
MHz, DMSO-d6) δ 11.64 (s, 1H), 7.41 (dd, J = 6.5, 3.0 Hz, 2H), 7.34–7.28 (m, 3H), 7.19 (d, J = 8.3 Hz, 1H), 7.12
(d, J = 8.4 Hz, 1H), 6.95 (d, J = 8.2 Hz, 2H), 6.87–6.78 (m, 3H), 6.53 (s, 1H), 2.24 (s, 3H), 2.17 (s, 3H), 13C NMR
(101 MHz, DMSO-d6) δ 154.6, 141.8, 139.0, 136.5, 130.1, 129.9, 129.7, 129.4, 128.8, 128.2, 128.1, 126.8, 125.5,
119.2, 116.9, 20.2. HRMS (ESI): calcd for C21H20N2O [M + H]+ 317.1648, found 317.1654.
(E)-(5-Chloro-2-(p-tolylamino)phenyl)(phenyl)methanone oxime (2p): yellow oil, (0.280 g, 29%). 1H NMR (400
MHz, DMSO-d6) δ 11.73 (s, 1H), 7.43–7.38 (m, 2H), 7.35–7.29 (m, 4H), 7.21 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 2.4
Hz, 1H), 6.99 (d, J = 8.1 Hz, 2H), 6.85 (d, J = 8.2 Hz, 2H), 6.82 (s, 1H), 2.19 (s, 3H), 13C NMR (101 MHz,
DMSO-d6) δ 153.0, 140.9, 140.5, 135.7, 129.6, 129.4, 129.3, 129.1, 129.0, 128.3, 126.6, 125.7, 123.3, 119.2, 118.5,
20.3. HRMS (ESI): calcd for C20H17ClN2O [M + H]+ 337.1102, found 337.1114.
(E)-(4-Fluorophenyl)(2-(p-tolylamino)phenyl)methanone oxime (2q): bright yellow oil, (0.320 g, 25%). 1H NMR
(400 MHz, DMSO-d6) δ 11.67 (s, 1H), 7.46–7.38 (m, 2H), 7.28 (dt, J = 16.0, 8.0 Hz, 2H), 7.14 (t, J = 8.8 Hz, 2H),
7.05 (d, J = 7.4 Hz, 1H), 7.01-6.92 (m, 3H), 6.85 (d, J = 8.2 Hz, 2H), 6.73 (s, 1H), 2.19 (s, 3H), 13C NMR (101
MHz, DMSO-d6) δ 163.0 (d, J = 246.0 Hz), 154.0, 142.1, 141.5, 133.4 (d, J = 2.8 Hz), 130.6, 129.9, 129.9, 129.4,
129.3 (d, J = 8.4 Hz), 124.8, 120.8, 118.6, 118.4, 115.6 (d, J = 21.7 Hz), 20.7, 19F NMR (376 MHz, DMSO-d6) δ
-112.90 (m). HRMS (ESI): calcd for C20H17FN2O [M + H]+ 321.1398, found 321.1405.
1
(E)-1-(2-(p-Tolylamino)phenyl)propan-1-one oxime (2r): yellow oil, (0.738 g, 76%). H NMR (400 MHz,
DMSO-d6) δ 11.20 (s, 1H), 9.28 (s, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.21-7.13 (m, 2H), 7.09 (d, J = 8.1 Hz, 2H), 7.00
(d, J = 8.2 Hz, 2H), 6.86-6.80 (m, 1H), 2.76 (q, J = 7.5 Hz, 2H), 2.25 (s, 3H), 1.06 (t, J = 7.5 Hz, 3H), 13C NMR
(101 MHz, DMSO-d6) δ 160.5, 142.9, 139.6, 130.5, 129.7, 129.1, 128.9, 120.8, 119.9, 118.4, 115.4, 20.3, 19.4, 11.0.
HRMS (ESI): calcd for C16H18N2O [M + H]+ 255.1492, found 255.1506.
(E)-1-(2-(Benzylamino)phenyl)ethan-1-one oxime (2t)ꢀyellow oil, (0.460 g, 69%). 1H NMR (400 MHz,
DMSO-d6) δ 11.12 (s, 1H), 8.18 (t, J = 5.5 Hz, 1H), 7.39 (d, J = 7.7 Hz, 1H), 7.34 (d, J = 4.3 Hz, 4H), 7.28-7.21 (m,
14

1H), 7.09 (t, J = 7.6 Hz, 1H), 6.66–6.57 (m, 2H), 4.42 (d, J = 5.8 Hz, 2H), 2.24 (s, 3H), 13C NMR (101 MHz,
DMSO-d6) δ 156.4, 146.4, 139.6, 129.2, 128.8, 128.5, 126.9, 126.8, 118.4, 115.0, 46.4, 12.3. HRMS (ESI): calcd
for C15H16N2O [M + H]+ 241.1335, found 241.1329.
1
(E)-1-(2-((4-Methylbenzyl)amino)phenyl)ethan-1-one oxime (2u): yellow oil, (0.370 g, 64%). H NMR (400
MHz, DMSO-d6) δ 11.09 (s, 1H), 8.12 (s, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 7.8 Hz, 2H), 7.14 (d, J = 7.7
Hz, 2H), 7.08 (t, J = 7.6 Hz, 1H), 6.64-6.57 (m, 2H), 4.35 (s, 2H), 2.27 (s, 3H), 2.23 (s, 3H), 13C NMR (101 MHz,
DMSO-d6) δ 156.9, 146.9, 137.0, 136.3, 129.7, 129.5, 129.2, 127.4, 118.8, 115.4, 111.4, 46.7, 21.1, 12.8. HRMS
(ESI): calcd for C16H18N2O [M + H]+ 255.1492, found 255.1505.
(E)-1-(2-((4-(Trifluoromethyl)benzyl)amino)phenyl)ethan-1-one oxime (2v): yellow oil, (0.360 g, 61%). 1H NMR
(400 MHz, DMSO-d6) δ 11.23–11.10 (m, 1H), 8.30 (s, 1H), 7.69 (d, J = 8.1 Hz, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.40
(d, J = 7.8 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 6.63 (t, J = 7.5 Hz, 1H), 6.55 (d, J = 8.3 Hz, 1H), 4.54 (s, 2H), 2.26 (s,
3H), 13C NMR (101 MHz, DMSO-d6) δ 156.4, 146.2, 144.9, 129.2, 128.8, 127.5 (q, J = 31.31 Hz), 127.5, 125.3 (q,
J = 3.03 Hz), 124.4 (q, J = 272.7 Hz), 118.6, 115.3, 110.9, 45.9, 12.3. HRMS (ESI): calcd for C16H15F3N2O [M +
H]+ 309.1209, found 309.1221.
4.1.3 General Procedure for the Synthesis of N-ArylBenzimidazoles (Reaction conditions A)
To a round-bottom flask equipped with a reflux condenser and a magnetic bar were added the BTC (0.2 mmol,
0.4 eq.) PhCl (4 mL). The reaction was stirred at ambient temperature for 15 min, then a solution of Oxime 1 (0.5
mmol, 1 eq.) in PhCl (4 mL) was added slowly and the reaction was keep in ambient temperature for 3 h unless
otherwise stated. Then, the mixture was quenched by saturated NaHCO3 solution and extracted with CH2Cl2 (10
mL x 3). The combined organic phase was dried over Na2SO4 and filtered. After evaporation of the solvents, the
residue was purified by silica gel chromatography (20% EtOAc/hexanes) to afford N-Arylbenzimidazole 3.
1
2-Methyl-1-phenyl-1H-benzo[d]imidazole (3a) 25: yellow solid, (0.098 g, 94%), m.p. 49.2~50.8°C. H NMR (400
MHz, CDCl3) δ 7.77 (d, J = 7.9 Hz, 1H), 7.59 (t, J = 7.4 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.38 (d, J = 7.4 Hz, 2H),
7.29 (d, J = 5.8 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H), 7.14 (d, J = 7.9 Hz, 1H), 2.53 (s, 3H), 13C NMR (101 MHz,
CDCl3) δ 151.6, 142.7, 136.6, 136.2, 130.0, 128.9, 127.2, 122.7, 122.5, 119.1, 110.0, 14.5. HRMS (ESI): calcd for
C14H12N2 [M + H]+ 209.1073, found 209.1085.
2-Methyl-1-(p-tolyl)-1H-benzo[d]imidazole (3b)26: yellow solid, (0.105 g, 93%), m.p. 89.5~90.7°C. 1H NMR (400
MHz, CDCl3) δ 7.76 (d, J = 7.9 Hz, 1H), 7.37 (d, J = 7.9 Hz, 2H), 7.30-7.23 (m, 3H), 7.18 (t, J = 7.5 Hz, 1H), 7.12
15

(d, J = 7.9 Hz, 1H), 2.51 (s, 3H), 2.48 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 151.6, 142.6, 138.8, 136.6, 133.4,
130.5, 126.8, 122.4, 122.2, 118.9, 109.9, 21.2, 14.4. HRMS (ESI): calcd for C15H14N2 [M + H]+ 223.1229, found
223.1235.
1-(4-Methoxyphenyl)-2-methyl-1H-benzo[d]imidazole (3c)27: tan solid, (0.111 g, 93%), m.p. 121.7~122.8°C.1H
NMR (400 MHz, DMSO-d6) δ 7.61 (d, J = 7.6 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.21-7.13 (m, 4H), 7.06 (d, J =
7.5 Hz, 1H), 3.85 (s, 3H), 2.39 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 159.2, 151.6, 142.3, 136.4, 128.2, 128.1,
122.1, 121.7, 118.4, 115.1, 109.7, 55.5, 14.0. HRMS (ESI): calcd for C15H14N2O [M + H]+ 239.1178, found
239.1081.
1
1-(4-Chlorophenyl)-2-methyl-1H-benzo[d]imidazole (3d)28: yellow solid, (0.111 g, 91%), m.p. 99.3~100.5°C. H
NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.9 Hz, 1H), 7.52 (d, J = 8.5 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 7.23 (d, J =
8.0 Hz, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.06 (d, J = 7.9 Hz, 1H), 2.47 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 151.4,
142.7, 136.4, 134.9, 134.7, 130.3, 128.5, 122.9, 122.7, 119.2, 109.8, 14.5. HRMS (ESI): calcd for C14H11ClN2 [M
+ H]+ 243.0683, found 243.0691.
1
1-(4-Fluorophenyl)-2-methyl-1H-benzo[d]imidazole (3e): tan solid, (0.099 g, 88%), m.p. 78.4~79.6°C. H NMR
(400 MHz, CDCl3) δ 7.73 (d, J = 7.9 Hz, 1H), 7.35-7.31 (m, 2H), 7.27–7.23 (m, 3H), 7.18 (t, J = 7.5 Hz, 1H), 7.06
(d, J = 8.0 Hz, 1H), 2.47 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 162.5 (d, J = 249.5 Hz), 151.6, 142.6, 136.6,
132.1 (d, J = 2.9 Hz), 129.0 (d, J = 8.7 Hz), 122.8, 122.6, 119.1, 117.0 (d, J = 22.9 Hz), 109.8, 14.4, 19F NMR (376
MHz, CDCl3) δ -111.74 (m). HRMS (ESI): calcd for C14H11FN2 [M + H]+ 227.0979, found 227.0982.
2-Methyl-1-(4-nitrophenyl)-1H-benzo[d]imidazole (3f): brown oil, (0.098 g, 77%). 1H NMR (400 MHz, CDCl3) δ
8.46 (d, J = 8.8 Hz, 2H), 7.76 (d, J = 7.9 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.24 (d, J = 7.3
Hz, 1H), 7.16 (d, J = 7.9 Hz, 1H), 2.57 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 150.8, 147.5, 142.8, 141.8, 135.7,
127.7, 125.6, 123.5, 123.4, 119.6, 109.7, 14.8. HRMS (ESI): calcd for C14H11N3O2 [M + H]+ 254.0924, found
254.0932.
1
2-Methyl-1-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole (3g): colorless oil, (0.105g, 76%). H NMR (400
MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.76 (d, J = 7.9 Hz, 1H), 7.52 (d, J = 8.2 Hz, 2H), 7.29 (t, J = 6 Hz 1H),
7.22 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 2.53 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 151.1, 142.8, 139.4,
136.1, 131.0 (q, J = 33.4 Hz), 127.5,127.3 (q, J = 3.0 Hz) 123.7 (q, J = 272.7 Hz),123.1, 122.9, 119.4, 109.7, 14.6,
1：

19F NMR (376 MHz, CDCl3) δ -62.58. HRMS (ESI): calcd for C15H11F3N2 [M + H]+ 277.0947, found 277.0952.
1-(3-Methoxyphenyl)-2-methyl-1H-benzo[d]imidazole (3h)29: yellow solid, (0.109g, 91%), m.p. 131.8~132.9°C.
1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz, 1H), 7.56 (t, J = 8.1 Hz, 1H), 7.37-7.33 (m, 1H), 7.31-7.24 (m,
2H), 7.15–7.13 (m, 1H), 7.04 (d, J = 7.8 Hz, 1H), 7.00-6.98 (m, 1H), 3.95 (s, 3H), 2.62 (s, 3H), 13C NMR (101
MHz, CDCl3) δ 160.8, 151.5, 142.6, 137.2, 136.5, 130.7, 122.6, 122.4, 119.3, 119.0, 114.4, 113.0, 110.1, 55.6, 14.5.
HRMS (ESI): calcd for C15H14N2O [M + H]+ 239.1178, found 239.1186.
1
1-(3-Chlorophenyl)-2-methyl-1H-benzo[d]imidazole (3i)26: yellow solid, (0.113 g, 93%), m.p. 165.3-166.4°C. H
NMR (400 MHz, DMSO-d6) δ 7.74 (s, 1H), 7.69-7.62 (m, 3H), 7.54 (d, J = 6.8 Hz, 1H), 7.24–7.19 (m, 2H), 7.15 (t,
J = 7.8 Hz, 1H), 2.44 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 151.2, 142.3, 137.0, 135.8, 134.1, 131.5, 128.8,
127.0, 125.9, 122.5, 122.1, 118.5, 109.7, 14.1. HRMS (ESI): calcd for C14H11ClN2 [M + H]+ 243.0683, found
243.0694.
1
1-(3-Fluorophenyl)-2-methyl-1H-benzo[d]imidazole (3j): yellow solid, (0.104 g, 92%), m.p. 127.4~128.7°C. H
NMR (400 MHz, CDCl3) δ 7.74 (d, J = 7.9 Hz, 1H), 7.55 (q, J = 8.0 Hz, 1H), 7.29-7.17 (m, 4H), 7.16–7.09 (m,
2H), 2.52 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 163.1 (d, J = 249.7 Hz), 151.2, 142.6, 137.5 (d, J = 9.7 Hz),
136.2, 131.2 (d, J = 9.1 Hz), 122.9, 122.9, 122.7, 119.2, 116.0 (d, J = 21.0 Hz), 114.6 (d, J = 23.0 Hz), 109.8, 14.4,
19F NMR (376 MHz, CDCl3) δ -109.80 (m). HRMS (ESI): calcd for C14H11FN2 [M + H]+ 227.0979, found
227.0985.
1-(2-Methoxyphenyl)-2-methyl-1H-benzo[d]imidazole (3k)26: yellow solid, (0.109 g, 91%), m.p.
123.3~124.9°C.1H NMR (400 MHz, CDCl3) δ 7.73 (d, J = 7.9 Hz, 1H), 7.52–7.45 (m, 1H), 7.29 (d, J = 6.8 Hz,
1H), 7.23 (t, J = 7.6 Hz, 1H), 7.17-7.10 (m, 3H), 6.98 (d, J = 8.0 Hz, 1H), 3.73 (s, 3H), 2.41 (s, 3H), 13C NMR (101
MHz, CDCl3) δ 155.3, 152.8, 142.8, 136.8, 130.7, 129.3, 124.5, 122.3, 122.1, 121.2, 118.9, 112.5, 110.0, 55.7, 14.0.
HRMS (ESI): calcd for C15H14N2O [M + H]+ 239.1179, found 239.1184.
1
1-(2-Chlorophenyl)-2-methyl-1H-benzo[d]imidazole (3l)26: yellow solid, (0.110 g, 90%),m.p. 72.8~73.6°C. H
NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.0 Hz, 1H), 7.68–7.61 (m, 1H), 7.54–7.44 (m, 2H), 7.42–7.36 (m, 1H),
7.27 (t, J = 7.5 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H), 2.43 (s, 3H), 13C NMR (101 MHz,
CDCl3) δ 151.9, 142.8, 136.3, 133.8, 133.3, 131.1, 130.9, 130.1, 128.3, 122.8, 122.6, 119.2, 109.9, 14.1. HRMS
(ESI): calcd for C14H11ClN2 [M + H]+ 243.0683, found 243.0692
17

1-(2-Fluorophenyl)-2-methyl-1H-benzo[d]imidazole (3m): brown oil, (0.101 g, 89%). 1H NMR (400 MHz, CDCl3)
δ 7.75 (d, J = 7.9 Hz, 1H), 7.54–7.49 (m, 1H), 7.42-7.38 (m, 1H), 7.36-7.32 (m, 2H), 7.27 (t, J = 7.4 Hz, 1H), 7.20
(t, J = 7.5 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 2.48 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 157.7 (d, J = 252.6 Hz),
152.0, 142.8, 136.3, 130.9 (d, J = 7.7 Hz), 129.4, 125.2 (d, J = 3.9 Hz), 123.8 (d, J = 13.0 Hz), 122.8, 122.5, 119.1,
117.3 (d, J = 19.6 Hz), 109.7, 13.9, 19F NMR (376 MHz, CDCl3) δ -120.21(m). HRMS (ESI): calcd for C14H11FN2
[M + H]+ 227.0979, found 227.0984.
1
2-Phenyl-1-(p-tolyl)-1H-benzo[d]imidazole (3n): yellow oil, (0.126 g, 88%). H NMR (400 MHz, CDCl3) δ 7.93
(d, J = 8.0 Hz, 1H), 7.64 (d, J = 7.0 Hz, 2H), 7.39-7.28 (m, 8H), 7.23 (d, J = 8.1 Hz, 2H), 2.48 (s, 3H), 13C NMR
(101 MHz, CDCl3) δ 152.5, 143.1, 138.7, 137.5, 134.5, 130.6, 130.2, 129.6, 129.5, 128.4, 127.3, 123.3, 123.0,
119.9, 110.6, 21.4. IR (neat) ṽꢀ=ꢀ1608, 1514ꢀcm−1. HRMS (ESI): calcd for C20H16N2 [M + H]+ 285.1386, found
285.1391.
1
5-Methyl-2-phenyl-1-(p-tolyl)-1H-benzo[d]imidazole (3o): yellow solid, (0.130 g, 87%), m.p. 152.3~154.7°C. H
NMR (400 MHz, CDCl3) δ 7.64 (s, 1H), 7.55 (d, J = 7.1 Hz, 2H), 7.32-7.28 (m, 2H), 7.25–7.22 (m, 3H), 7.14 (d, J
= 8.0 Hz, 2H), 7.06 (q, J = 8.3 Hz, 2H), 2.48 (s, 3H), 2.40 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 152.4, 143.4,
138.5, 135.6, 134.6, 132.7, 130.5, 130.3, 129.5, 129.4, 128.3, 127.2, 124.8, 119.6, 110.1, 21.7, 21.3. IR (neat)
ṽꢀ=ꢀ1616, 1515ꢀcm−1. HRMS (ESI): calcd for C21H18N2 [M + H]+ 299.1543, found 299.1547.
1
5-Chloro-2-phenyl-1-(p-tolyl)-1H-benzo[d]imidazole (3p): yellow solid, (0.138 g, 86%), m.p. 144.8~145.7 °C. H
NMR (400 MHz, CDCl3) δ 7.89–7.85 (m, 1H), 7.59 (d, J = 7.2 Hz, 2H), 7.40-7.29 (m, 5H), 7.24-7.13 (m, 4H),
2.47 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 153.7, 143.8, 139.0, 136.2, 134.1, 130.7, 129.8, 129.7, 129.5, 128.5,
128.5, 127.1, 123.7, 119.6, 111.4, 21.4. IR (neat) ṽꢀ=ꢀ1611, 1506ꢀcm−1. HRMS (ESI): calcd for C20H15ClN2 [M +
H]+ 319.0997, found 319.1024
1
2-(4-Fluorophenyl)-1-(p-tolyl)-1H-benzo[d]imidazole (3q): yellow oil, (0.127 g, 84%). H NMR (400 MHz,
CDCl3) δ 7.87 (d, J = 8.0, Hz,1H), 7.58 (dd, J = 8.2, 5.6 Hz, 2H), 7.35-7.27 (m, 3H), 7.26–7.23 (m, 2H), 7.19 (t, J =
7.7 Hz, 2H), 7.00 (t, J = 8.5 Hz, 2H), 2.45 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 163.4 (d, J = 250.4 Hz), 151.5,
142.9, 138.8, 137.4, 134.2, 131.4 (d, J = 8.4 Hz), 130.6, 127.2, 126.3 (d, J = 3.1 Hz), 123.3, 123.0, 119.8, 115.5 (d,
J = 21.8 Hz), 110.5, 21.3, 19F NMR (376 MHz, CDCl3) δ -110.86 (m). IR (neat) ṽꢀ=ꢀ1608, 1507ꢀcm−1. HRMS (ESI):
calcd for C20H15FN2 [M + H]+ 303.1292, found 303.1325
18

2-Ethyl-1-(p-tolyl)-1H-benzo[d]imidazole (3r): yellow oil, (0.104 g, 89%). 1H NMR (400 MHz, CDCl3) δ 7.78 (d,
J = 7.9 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.27-7.22 (m, 3H), 7.17 (t, J = 7.5 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 2.79
(q, J = 7.5 Hz, 2H), 2.47 (s, 3H), 1.34 (t, J = 7.5 Hz, 3H), 13C NMR (101 MHz, CDCl3) δ 156.5, 142.6, 139.0,
136.8, 133.5, 130.6, 127.2, 122.5, 122.3, 119.2, 110.0, 21.3, 12.2. IR (neat) ṽꢀ=ꢀ1616, 1516ꢀcm−1. HRMS (ESI):
calcd for C16H16N2 [M + H]+ 237.1386, found 237.1398
2-Pentyl-1-(p-tolyl)-1H-benzo[d]imidazole (3s): yellow oil, (0.114 g, 82%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d,
J = 8.0 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.23 (t, J = 6.8 Hz, 3H), 7.17 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.0 Hz, 1H),
2.76 (t, J = 7.8 Hz, 2H), 2.47 (s, 3H), 1.74-1.82 (m, 2H), 1.26-1.31 (m, 4H), 0.84 (t, J = 6.9 Hz, 3H), 13C NMR
(101 MHz, CDCl3) δ 155.6, 142.7, 139.0, 136.8, 133.5, 130.6, 127.2, 122.5, 122.3, 119.1, 110.0, 31.6, 27.8, 27.6,
22.4, 21.3, 14.0. IR (neat) ṽꢀ=ꢀ1612, 1521ꢀcm−1. HRMS (ESI): calcd for C19H22N2 [M + H]+ 279.1856, found
279.1861
4.1.4 General Procedure for the Synthesis of Indazoles (Reaction conditions B)
To a round-bottom flask equipped with a reflux condenser and a magnetic bar were added the oxime (0.5
mmol, 1.0 eq.) and Et3N (3 mmol, 6 eq.), DCM (4 mL). The reaction was stirred at ambient temperature for 15 min,
then cooled to -5°C. A solution of BTC (0.375 mmol, 0.75 eq.) in DCM (6 mL) was added slowly and the reaction
was keep in -5 °C for 3 h unless otherwise stated. Then, the mixture was quenched by saturated NaHCO3 solution
and extracted with CH2Cl2 (10 mL x 3). The combined organic phase was dried over Na2SO4 and filtered. After
evaporation of the solvents, the residue was purified by silica gel chromatography (3% EtOAc/hexanes) to afford
N-Arylindazole 4.
1
3-Methyl-1-phenyl-1H-indazole (4a)30: yellow solid, (0.093 g, 89%), m.p. 72.8~73.7°C. H NMR (400 MHz,
DMSO-d6) δ 7.81 (t, J = 9.2 Hz, 2H), 7.74 (d, J = 7.8 Hz, 2H), 7.56 (t, J = 7.9 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1H),
7.35 (t, J = 7.4 Hz, 1H), 7.24 (t, J = 7.4 Hz, 1H), 2.58 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 144.1, 140.3,
139.2, 130.0, 128.0, 126.4, 125.0, 122.0, 121.5, 121.3, 110.8, 12.1. HRMS (ESI): calcd for C14H12N2 [M + H]+
209.1073, found 209.1085.
1
3-Methyl-1-(p-tolyl)-1H-indazole (4b): yellow oil, (0.100 g, 90%). H NMR (400 MHz, CDCl3) δ 7.70 (dd, J =
18.7, 8.3 Hz, 2H), 7.59 (d, J = 8.2 Hz, 2H), 7.41 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.20 (t, J = 7.5 Hz,
1H), 2.67 (s, 3H), 2.43 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 143.7, 139.7, 138.0, 136.1, 130.1, 127.1, 124.8,
122.6, 120.7, 120.7, 110.4, 21.2, 12.1. HRMS (ESI): calcd for C15H14N2 [M + H]+ 223.1229, found 223.1234.
19

1
1-(4-Methoxyphenyl)-3-methyl-1H-indazole (4c)31: yellow solid, (0.110 g, 92%), m.p. 48.7~49.9°C. H NMR
(400 MHz, CDCl3) δ 7.72 (d, J = 8.0 Hz, 1H), 7.64–7.57 (m, 3H), 7.39 (t, J = 7.6 Hz, 1H), 7.19 (t, J = 7.4 Hz, 1H),
7.04 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.66 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 158.2, 143.4, 139.8, 133.6,
127.0, 124.6, 124.3, 120.6, 114.7, 110.2, 55.7, 12.0. HRMS (ESI): calcd for C15H14N2O [M + H]+ 239.1178, found
239.1083.
1-(4-Chlorophenyl)-3-methyl-1H-indazole (4d): yellow oil, (0.088 g, 72%). 1H NMR (400 MHz, CDCl3) δ 7.73 (d,
J = 8.0 Hz, 1H), 7.67 (d, J = 8.7 Hz, 3H), 7.48 (d, J = 8.7 Hz, 2H), 7.43 (t, J = 7.8 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H),
2.65 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 144.6, 139.5, 139.0, 131.5, 129.6, 127.5, 125.2, 123.4, 121.2, 120.9,
110.2, 12.0. HRMS (ESI): calcd for C14H11ClN2 [M + H]+ 243.0683, found 243.0697.
1
1-(4-Fluorophenyl)-3-methyl-1H-indazole (4e): pale yellow oil, (0.084 g, 74%). H NMR (400 MHz, CDCl3) δ
7.73 (d, J = 8.0 Hz, 1H), 7.69-7.60 (m, 3H), 7.42 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 8.2 Hz, 3H), 2.66 (s, 3H), 13C
NMR (101 MHz, CDCl3) δ 160.9 (d, J = 245.8 Hz), 144.1, 139.7, 136.6 (d, J = 2.4 Hz), 127.4, 124.91, 124.3 (d, J =
8.3 Hz), 121.0, 120.8, 116.3 (d, J = 22.9 Hz), 110.1, 12.0, 19F NMR (376 MHz, CDCl3) δ -115.79 (m). HRMS
(ESI): calcd for C14H11FN2 [M + H]+ 227.0979, found 227.0986.
3-Methyl-1-(4-nitrophenyl)-1H-indazole (4f): yellow oil, (0.089 g, 35%). 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J
= 8.9 Hz, 2H), 7.94 (d, J = 8.9 Hz, 2H), 7.82 (d, J = 8.5 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H),
7.30 (t, J = 7.5 Hz, 1H), 2.66 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 146.8, 145.7, 144.6, 139.4, 128.4, 126.3,
125.4, 122.3, 121.3, 120.7, 110.7, 12.1. HRMS (ESI): calcd for C14H11N3O2 [M + H]+ 254.0924, found 254.0936.
3-Methyl-1-(4-(trifluoromethyl)phenyl)-1H-indazole (4g): yellow oil, (0.152 g, 55%). 1H NMR (400 MHz, CDCl3)
δ 7.87 (d, J = 8.4 Hz, 2H), 7.74 (t, J = 9.0 Hz, 4H), 7.46 (t, J = 7.7 Hz, 1H), 7.25 (t, J = 7.8 Hz, 1H), 2.65 (s, 3H),
13C NMR (101 MHz, CDCl3) δ 145.4, 143.2, 139.3, 127.7, 127.5 (q, J = 33.3 Hz),126.6 (q, J = 3.0 Hz), 125.6,
124.1 (q, J = 273.7 Hz), 121.5, 121.4, 120.9, 110.3, 11.9, 19F NMR (376 MHz, CDCl3) δ -62.11. HRMS (ESI):
calcd for C15H11F3N2 [M + H]+ 277.0947, found 277.0956.
1-(3-Methoxyphenyl)-3-methyl-1H-indazole (4h): yellow oil, (0.103 g, 86%). 1H NMR (400 MHz, CDCl3) δ 7.74
(t, J = 8.9 Hz, 2H), 7.46-7.37 (m, 2H), 7.35–7.28 (m, 2H), 7.21 (t, J = 7.4 Hz, 1H), 6.91–6.85 (m, 1H), 3.89 (s, 3H),
2.67 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 160.6, 144.1, 141.5, 139.6, 130.2, 127.3, 125.1, 121.0, 120.7, 114.5,
112.1, 110.6, 108.2, 55.6, 12.0. HRMS (ESI): calcd for C15H14N2O [M + H]+ 239.1178, found 239.1191.
20

1-(3-Chlorophenyl)-3-methyl-1H-indazole (4i): yellow oil, (0.083 g, 68%). 1H NMR (400 MHz, CDCl3) δ 7.77 (s,
1H), 7.72 (d, J = 8.5 Hz, 2H), 7.63 (d, J = 8.0 Hz, 1H), 7.44 (q, J = 7.9, 7.2 Hz, 2H), 7.28 (d, J = 8.4 Hz, 1H), 7.23
(t, J = 7.5 Hz, 1H), 2.65 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 144.9, 141.6, 139.5, 135.2, 130.5, 127.6, 126.0,
125.4, 122.3, 121.3, 120.9, 120.0, 110.4, 12.0. HRMS (ESI): calcd for C14H11ClN2 [M + H]+ 243.0683, found
243.0687.
1
1-(3-Fluorophenyl)-3-methyl-1H-indazole (4j): yellow oil, (0.074 g, 65%). H NMR (400 MHz, CDCl3) δ 7.77–
7.70 (m, 2H), 7.54 (d, J = 8.0 Hz, 1H), 7.51–7.42 (m, 3H), 7.26–7.20 (m, 1H), 7.04–6.97 (m, 1H), 2.66 (s, 3H), 13
C
NMR (101 MHz, CDCl3) δ 163.37 (d, J = 246.6 Hz), 144.8, 141.96 (d, J = 10.3 Hz), 139.5, 130.7 (d, J = 9.3 Hz),
127.6, 125.4, 121.3, 120.9, 117.4(d, J = 2.0 Hz), 112.8 (d, J = 21.1 Hz), 110.5, 109.6 (d, J = 25.1 Hz), 12.1, 19F
NMR (376 MHz, CDCl3) δ -111.05 (m). HRMS (ESI): calcd for C14H11FN2 [M + H]+ 227.0979, found 227.0988.
1-(2-Methoxyphenyl)-3-methyl-1H-indazole (4k): yellow oil, (0.101 g, 84%). 1H NMR (400 MHz, CDCl3) δ 7.72
(d, J = 8.0 Hz, 1H), 7.50–7.46 (m, 1H), 7.43-7.34 (m, 2H), 7.19 (dd, J = 17.0, 8.3 Hz, 2H), 7.12-7.08 (m, 2H), 3.79
(s, 3H), 2.68 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 154.3, 143.6, 141.4, 129.2, 128.63, 128.56,126.5, 123.9,
121.0, 120.2, 112.3, 111.1, 55.8, 12.1. HRMS (ESI): calcd for C15H14N2O [M + H]+: 239.1179, found 239.1185.
1-(2-Chlorophenyl)-3-methyl-1H-indazole (4l): yellow oil, (0.088 g, 72%). 1H NMR (400 MHz, CDCl3) δ 7.74 (d,
J = 8.2 Hz, 1H), 7.60-7.58 (m, 1H), 7.54–7.49 (m, 1H), 7.44–7.36 (m, 3H), 7.23-7.20 (m, 2H), 2.68 (s, 3H), 13C
NMR (101 MHz, CDCl3) δ 144.4, 141.2, 137.4, 131.5, 130.7, 129.7, 129.6, 127.7, 127.0, 124.1, 120.7, 120.5,
110.7, 12.1. HRMS (ESI): calcd for C14H11ClN2 [M + H]+ 243.0683, found 243.0691.
1
1-(2-Fluorophenyl)-3-methyl-1H-indazole (4m): brown oil, (0.073 g, 64%). H NMR (400 MHz, CDCl3) δ 7.73
(d, J = 8.0 Hz, 1H), 7.62 (t, J = 7.7 Hz, 1H), 7.45–7.40 (m, 1H), 7.39–7.33 (m, 2H), 7.30 (t, J = 7.7 Hz, 2H), 7.22 (t,
J = 7.4 Hz, 1H), 2.67 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 156.2 (d, J = 251.8 Hz), 144.9, 141.1, 128.9 (d, J =
7.6 Hz), 128.0, 127.8 (d, J = 11.6 Hz), 127.2, 125.0 (d, J = 3.4 Hz), 124.5, 120.9, 120.5, 117.0 (d, J = 19.7 Hz),
110.6 (d, J = 4.9 Hz), 12.1, 19F NMR (376 MHz, CDCl3) δ -120.40 (m). HRMS (ESI): calcd for C14H11FN2 [M +
H]+ 227.0979, found 227.0993.
1
3-Phenyl-1-(p-tolyl)-1H-indazole (4n): yellow solid, (0.120 g, 84%), m.p. 91.5~92.7°C. H NMR (400 MHz,
CDCl3) δ 8.13-8.03 (m, 3H), 7.76 (d, J = 8.5 Hz, 1H), 7.69 (d, J = 8.1 Hz, 2H), 7.55 (t, J = 7.5 Hz, 2H), 7.49–7.42
(m, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.29 (t, J = 7.5 Hz, 1H), 2.46 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 145.9,
21

140.5, 137.8, 136.7, 133.5, 130.1, 128.9, 128.3, 127.9, 127.1, 123.2, 123.1, 121.9, 121.7, 110.8, 21.2. IR (neat)
ṽꢀ=ꢀ1603, 1511ꢀcm−1. HRMS (ESI): calcd for C20H16N2 [M + H]+ 285.1386, found 285.1396.
1
5-Methyl-3-phenyl-1-(p-tolyl)-1H-indazole (4o): yellow solid, (0.123 g, 82%), m.p. 99.8~101.2°C. H NMR (400
MHz, CDCl3) δ 8.05 (d, J = 7.7 Hz, 2H), 7.86 (s, 1H), 7.71–7.62 (m, 3H), 7.54 (t, J = 7.6 Hz, 2H), 7.43 (t, J = 7.3
Hz, 1H), 7.35 (d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.7 Hz, 1H), 2.53 (s, 3H), 2.45 (s, 3H), 13C NMR (101 MHz, CDCl3)
δ 145.3, 139.2, 138.0, 136.5, 133.7, 131.4, 130.1, 129.1, 128.9, 128.2, 127.9, 123.5, 122.9, 120.7, 110.5, 21.6, 21.2.
IR (neat) ṽꢀ=ꢀ1616, 1508ꢀcm−1. HRMS (ESI): calcd for C21H18N2 [M + H]+ 299.1543, found 299.1568.
1
5-Chloro-3-phenyl-1-(p-tolyl)-1H-indazole (4p): yellow solid, (0.114 g, 71%), m.p. 90.5~91.8°C. H NMR (400
MHz, CDCl3) δ 8.04 (s, 1H), 7.99 (d, J = 7.4 Hz, 2H), 7.64 (t, J = 8.9 Hz, 3H), 7.54 (t, J = 7.5 Hz, 2H), 7.44 (t, J =
7.4 Hz, 1H), 7.41–7.33 (m, 3H), 2.45 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 145.4, 139.0, 137.4, 137.2, 132.9,
130.2, 129.1, 128.6, 127.8, 127.7, 127.6, 123.9, 123.2, 120.9, 111.9, 21.3. IR (neat) ṽꢀ=ꢀ1613, 1508ꢀcm−1. HRMS
(ESI): calcd for C20H15ClN2 [M + H]+: 319.0997, found 319.1028.
1
3-(4-Fluorophenyl)-1-(p-tolyl)-1H-indazole (4q): yellow solid, (0.117 g, 77%), m.p. 115.9~117.1°C. H NMR
(400 MHz, CDCl3) δ 8.00-7.97 (m, 3H), 7.70 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 8.2 Hz, 2H), 7.40 (t, J = 7.7 Hz, 1H),
7.31 (d, J = 8.1 Hz, 2H), 7.27–7.17 (m, 3H), 2.41 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 162.9 (d, J = 247.4 Hz),
144.8, 140.4, 137.6, 136.7, 130.1, 129.6 (d, J = 3.2 Hz), 129.4 (d, J = 8.1 Hz), 127.1, 123.0, 122.8, 121.9, 121.3,
115.8 (d, J = 21.5 Hz), 110.8, 21.1, 19F NMR (376 MHz, CDCl3) δ -113.46 (m). IR (neat) ṽꢀ=ꢀ1610, 1517ꢀcm−1.
HRMS (ESI): calcd for C20H15FN2 [M + H]+ 303.1292, found 303.1312.
1
3-Ethyl-1-(p-tolyl)-1H-indazole (4r): yellow oil, (0.098 g, 83%). H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.1
Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 8.1 Hz, 2H), 7.40 (t, J = 7.7 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.19 (t,
J = 7.5 Hz, 1H), 3.10 (q, J = 7.6 Hz, 2H), 2.43 (s, 3H), 1.48 (t, J = 7.6 Hz, 3H), 13C NMR (101 MHz, CDCl3) δ
149.1, 139.8, 138.0, 136.0, 130.0, 127.0, 124.0, 122.6, 120.7, 120.6, 110.5, 21.2, 20.6, 13.8. IR (neat) ṽꢀ=ꢀ1618,
1508ꢀcm−1. HRMS (ESI): calcd for C16H16N2 [M + H]+ 237.1386, found 237.1392.
1
3-Pentyl-1-(p-tolyl)-1H-indazole (4s): yellow oil, (0.110 g, 79%). H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.1
Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 8.2 Hz, 2H), 7.40 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.1 Hz, 2H), 7.19 (t,
J = 7.5 Hz, 1H), 3.06 (t, J = 7.8 Hz, 2H), 2.43 (s, 3H), 1.95-1.85 (m, 2H), 1.53–1.35 (m, 4H), 0.94 (t, J = 7.0 Hz,
3H), 13C NMR (101 MHz, CDCl3) δ 148.1, 139.8, 138.0, 136.0, 130.0, 126.9, 124.3, 122.6, 120.8, 120.6, 110.5,
22

32.0, 29.2, 27.23, 22.6, 21.2, 14.2. IR (neat) ṽꢀ=ꢀ1598, 1507 cm−1. HRMS (ESI): calcd for C19H22N2 [M + H]+
279.1856, found 279.1877.
1-Benzyl-3-methyl-1H-indazole (4t): yellow oil, (0.078 g, 70%). 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.1 Hz,
1H), 7.35–7.24 (m, 5H), 7.20 (d, J = 7.1 Hz, 2H), 7.12 (t, J = 7.2 Hz, 1H), 5.54 (s, 2H), 2.61 (s, 3H), 13C NMR
(101 MHz, CDCl3) δ 141.9, 140.6, 137.4, 128.8, 127.7, 127.2, 126.5, 123.9, 120.6, 119.9, 109.3, 52.7, 12.1. IR
(neat) ṽꢀ=ꢀ1615, 1508ꢀcm−1. HRMS (ESI): calcd for C15H14N2 [M + H]+ 223.1230, found 223.1229.
3-Methyl-1-(4-methylbenzyl)-1H-indazole (4u): yellow oil, (0.090 g, 76%). 1H NMR (400 MHz, CDCl3) δ 7.69 (d,
J = 8.1 Hz, 1H), 7.37–7.28 (m, 2H), 7.17–7.09 (m, 5H), 5.52 (s, 2H), 2.64 (s, 3H), 2.33 (s, 3H), 13C NMR (101
MHz, CDCl3) δ 141.7, 140.5, 137.3, 134.3, 129.4, 127.2, 126.3, 123.8, 120.5, 119.8, 109.3, 52.5, 21.1, 12.0. IR
(neat) ṽꢀ=ꢀ1614, 1508ꢀcm−1. HRMS (ESI): calcd for C16H16N2 [M + H]+ 237.1386, found 237.1380.
3-Methyl-1-(4-(trifluoromethyl)benzyl)-1H-indazole (4v): yellow oil, (0.094 g, 65%). 1H NMR (400 MHz, CDCl3)
δ 7.67 (d, J = 8.1 Hz, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.33 (t, J = 7.6 Hz, 1H), 7.27–7.21 (m, 3H), 7.13 (t, J = 7.4 Hz,
1H), 5.56 (s, 2H), 2.59 (s, 3H), 13C NMR (101 MHz, CDCl3) δ 142.6, 141.4, 140.7, 130.1 (q, J = 32.7 Hz), 127.4,
126.8, 125.8 (q, J = 3.03 Hz), 124.2 (q, J = 272.7 Hz), 124.0, 120.7, 120.2, 108.9, 52.1, 12.1, 19F NMR (376 MHz,
CDCl3) δ -62.53. IR (neat) ṽꢀ=ꢀ1617, 1509ꢀcm−1. HRMS (ESI): calcd for C16H13F3N2 [M + H]+ 291.1104, found
291.1099.
4.1.5 General Procedure for the Control experiments a
The reaction was performed according to the reaction conditions A using 0.55 g (3.0 mmol, 1 eq.) of
N-benzylaniline, 0.356 g (1.2 mmol, 0.4 eq.) of BTC to afford N-Arylbenzimidazole N-Benzyl-N-phenylcarbamoyl
chloride 6, the residue was purified by silica gel chromatography (5% EtOAc/hexanes) to afford the product.
N-Benzyl-N-phenylcarbamoyl chloride (6)32: white solid, (0.132 g, 18%), m.p. 44.6~45.8°C. 1H NMR (400 MHz,
CDCl3) δ 7.33–7.29 (m, 3H), 7.29–7.25 (m, 3H), 7.19 (br, 2H), 7.01 (br, 2H), 4.86 (s, 2H), 13C NMR (101 MHz,
CDCl3) δ 149.8, 141.6, 135.6, 129.4, 129.0, 128.7, 128.5, 128.2, 56.7.
4.1.6 General Procedure for the Control experiments b
The reaction was performed according to the reaction conditions A using 0.811 g (6.0 mmol, 1 eq.) of
(E)-1-phenylethan-1-one oxime, 1.015 g (6 mmol, 1 eq.) of Diphenylamine, 0.712 g (2.4 mmol, 0.4 eq.) of BTC to
afford (E)-1-Phenylethan-1-one-O-chlorocarbonyl oxime 9, the residue was purified by silica gel chromatography
23

(5% EtOAc/hexanes) to afford 79% of the product (0.940 g, 4.75 mmol).
The reaction was performed according to the reaction conditions B using 0.811 g (6.0 mmol, 1 eq.) of
(E)-1-phenylethan-1-one oxime, 1.015 g (6 mmol, 1 eq.) of Diphenylamine, 1.33 g (4.5mmol, 0.75 eq.) of BTC,
3.64 g (36mmol, 6 eq.) of Et3N to afford (E)-1-Phenylethan-1-one-O-chlorocarbonyl oxime 9, the residue was
purified by silica gel chromatography (5% EtOAc/hexanes) to afford 76% of the product (0.904 g, 4.57 mmol).
(E)-1-Phenylethan-1-one-O-chlorocarbonyl oxime (9)33: yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 7.79 (d, J
= 7.0 Hz, 2H), 7.56-7.48 (m, 3H), 2.44 (s, 3H), 13C NMR (101 MHz, DMSO-d6) δ 163.9, 151.3, 133.9, 130.9,
128.7, 126.9, 14.2. EI-MS: m/z 197 ([M + H]+ for 35Cl), 199 ([M + H]+ for 37Cl).
4.1.7 General Procedure for the Control experiments c
The reaction was performed according to the reaction conditions A using 0.159 g (0.80 mmol, 1 eq.) of
(E)-1-Phenylethan-1-one-O-chlorocarbonyl oxime 9, 0.095 g (0.32 mmol, 0.4 eq.) of BTC to afford Acetanilide 11,
the residue was purified by silica gel chromatography (20% EtOAc/hexanes) to afford 56% of the product (0.061 g,
0.45 mmol).
The reaction was performed according to the reaction conditions B using 0.159 g (0.80 mmol, 1 eq.) of
(E)-1-Phenylethan-1-one-O-chlorocarbonyl oxime 9, 0.179 g (0.60 mmol, 0.75 eq.) of BTC, 0.488 g (4.8 mmol, 6
eq.) of Et3N.
1
Acetanilide (11)34: White solid; (0.061 g, 56 %), m.p. 112.6~114.7°C. H NMR (400 MHz, DMSO-d6) δ 9.92 (s,
1H), 7.59 (d, J = 7.7 Hz, 2H), 7.28 (t, J = 7.8 Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 2.04 (s, 3H), 13C NMR (101 MHz,
DMSO-d6) δ 168.3, 139.3, 128.6, 123.0, 119.0, 24.0.
4.1.8 General Procedure for the Control experiments d
To a round-bottom flask equipped with a hydrochloric acid gas generator, reflux condenser and magnetic bar
were added the BTC (0.2 mmol, 0.4 eq.) PhCl (4 mL). The reaction was stirred under HCl atmosphere at ambient
temperature for 15 min, then a solution of Oxime 1 (0.5 mmol, 1 eq.) in PhCl (4 mL) was added slowly and the
reaction was keep in ambient temperature for 3 h. Then, the mixture was quenched by saturated NaHCO3 solution
and extracted with CH2Cl2 (10 mL x 3). The combined organic phase was dried over Na2SO4 and filtered. After
evaporation of the solvents, the residue was purified by silica gel chromatography (20% EtOAc/hexanes) to afford
54% of N-Arylbenzimidazole 3 (0.056 g, 0.27 mmol).
24

To a round-bottom flask equipped with a hydrochloric acid gas generator, reflux condenser and magnetic bar
were added the BTC (0.2 mmol, 0.4 eq.) PhCl (4 mL). The reaction was stirred under HCl atmosphere at ambient
temperature for 15 min, then a solution of Oxime 1 (0.5 mmol, 1 eq.) in PhCl (4 mL) was added slowly and the
reaction was keep in ambient temperature for 5 h. Then, the mixture was quenched by saturated NaHCO3 solution
and extracted with CH2Cl2 (10 mL x 3). The combined organic phase was dried over Na2SO4 and filtered. After
evaporation of the solvents, the residue was purified by silica gel chromatography (20% EtOAc/hexanes) to afford
92% of N-Arylbenzimidazole 3 (0.096 g, 0.46 mmol).
Acknowledgements
We thank the National Natural Science Foundation of China (Grant No. 21376221) for financial support.
Associated Content
Supporting Information
Copies of 1H, 13C and 19F NMR spectra of starting materials and all products.
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27

Highlights
ꢀ
A divergent synthesis of N-arylbenzimidazoles and N-arylindazoles from
arylamino oximes based on reaction conditions selection was developed.
ꢀ This switchable hectorcycle formation process features mild reaction conditions,
simple execution, high chemoselectivity and broad substrate scope.
ꢀ The chemoselectiyity of this synthesis was regulated by the amount of Et3N.