Efficient 2-aryl benzothiazole formation from acetophenones, anilines, and elemental sulfur by iodine-catalyzed oxidative C(CO)-C(alkyl) bond cleavage

Article abstract of DOI:10.1016/j.tet.2018.08.047

A novel and efficient iodine-catalyzed one-pot reaction of aromatic amines, acetophenones, and elemental sulfur for the synthesis of 2-aryl benzothiazoles is described. The process involves sequential C?S and C-N bond formation followed by C(CO)?C bond cleavage from readily accessible starting materials. A wide range of functional groups is tolerated under oxidant and metal-free condition and moderate to good product yields are obtained.

Full text of DOI:10.1016/j.tet.2018.08.047

Accepted Manuscript
Efficient 2-aryl benzothiazole formation from acetophenones, anilines, and elemental
sulfur by iodine-catalyzed oxidative C(CO)-C(alkyl) bond cleavage
Yafeng Liu, Xinglong Yuan, Xin Guo, Xueguo Zhang, Baohua Chen
PII:
S0040-4020(18)31030-5
10.1016/j.tet.2018.08.047
TET 29767
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 May 2018
Revised Date: 27 August 2018
Accepted Date: 28 August 2018
Please cite this article as: Liu Y, Yuan X, Guo X, Zhang X, Chen B, Efficient 2-aryl benzothiazole
formation from acetophenones, anilines, and elemental sulfur by iodine-catalyzed oxidative C(CO)-
C(alkyl) bond cleavage, Tetrahedron (2018), doi: 10.1016/j.tet.2018.08.047.
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Efficient 2-Aryl Benzothiazole Formation
from Acetophenones, Anilines, and
Leave this area blank for abstract info.
Elemental Sulfur by Iodine-Catalyzed
Oxidative C(CO)-C(alkyl) Bond Cleavage
Yafeng Liu, Xinglong Yuan, Xin Guo, Xueguo Zhang, and Baohua Chen
E-mail: chbh@lzu.edu.cn

1
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Tetrahedron
journal homepage: www.elsevier.com
Efficient 2-Aryl Benzothiazole Formation from Acetophenones, Anilines, and
Elemental Sulfur by Iodine-Catalyzed Oxidative C(CO)-C(alkyl) Bond Cleavage
Yafeng Liua, Xinglong Yuana, Xin Guoa, Xueguo Zhanga, and Baohua Chena*
aState Key Laboratory of Applied Organic Chemistry, Key laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Department
of Chemistry, Lanzhou University, Lanzhou, Gansu, China.
E-mail: chbh@lzu.edu.cn
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel and efficient iodine-catalyzed one-pot reaction of aromatic amines, acetophenones, and
elemental sulfur for the synthesis of 2-aryl benzothiazoles is described. The process involves
sequential C−S and C-N bond formation followed by C(CO)−C bond cleavage from readily
accessible starting materials. A wide range of functional groups is tolerated under oxidant and
metal-free condition and moderate to good product yields are obtained.
Available online
Keywords:
2009 Elsevier Ltd. All rights reserved
.
Benzothiazoles
Acetophenones
Anilines
Elemental sulfur
C−C bond cleavage
1. Introduction
Traditional methods for the construction of 2-aryl
benzothiazole skeleton involve the condensation of 2-
aminothiophenol with carbonyl compounds such as aldehydes,
carboxylic acids, acid chlorides and esters (Scheme 1, a).10
Another approach requires the preparation of 2-aryl
benzothiazoles via the reaction of 2-haloaniline and a sulfur
source11 or transition-metal-catalyzed intramolecular cyclization
of thiobenzanilide (Scheme 1, b)12. However, these methods have
Benzothiazole, as a privileged heterocyclic scaffold, is
frequently found in diverse natural products and
pharmacologically active molecules.1 In particular, 2-aryl
benzothiazoles have attracted increasing attention owing to its
broad pharmacological profile.2 For example, compound A
possesses highly potent antiproliferative activity.3 B exhibits
significant activity against clinically relevant pathogens E. coli
and S. aureus4 and C enables a invasive diagnosis of Alzheimer’s
disease.5 Furthermore, 2-aryl benzothiazoles can be employed as
therapeutic agents by the virtue of their antitumor,6 antiparasitic,7
anti-inflammatory,8 and anticonvulsant activities.9 Thus,
considerable research has been conducted on the synthesis of 2-
aryl benzothiazoles over the past few decades.
Figure 1. Pharmaceutical and bioactive compounds containing 2-
aryl benzothiazoles
Scheme 1. Synthesis of 2-aryl benzothiazoles

2
Tetrahedron
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[a]
Table 2. Scope of substituted anilines
Table 1. Optimization of reaction conditions
Yield[b]
Entry
Catalyst (mol %)
Additive
Solvent
（%）
1
2
I2 (15)
-
PhCl
PhCl
23
trace
66
I2 (50)
-
3
I2 (15)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
PhCl
4
NH4I (15)
PhCl
41
5
KI (15)
PhCl
47
6
TBAI (15)
PhCl
trace
81
7
I2(15)/TBAI (20)
I2(15)/TBAB(20)
I2(15)/TBAI (20)
I2(15)/TBAI (20)
I2(15)/TBAI (20)
I2(15)/TBAI (20)
I2(15)/TBAI (20)
I2(15)/TBAI (20)
PhCl
PhCl
8
75
9
DMSO
Toluene
NMP
PhCl
68
10
11
12[c]
13[d]
14[e]
51
42
64
PhCl
80
agent in this transformation. Hence, the optimal reaction
condition was established as shown in entry 7 (Table 1).
PhCl
69
aReaction conditions: 1a (0.4 mmol), 2a (0.2 mmol), S8 (4 equiv.), catalyst
(15 mol%), additive (0.15 mmol), Na2SO4 (5 equiv.), and solvent (0.6 ml)
under air at 140 C for 48h. Yields of isolated products. At 120 C. At
150 oC.eWithout Na2SO4.
With the optimal reaction conditions in hand, we investigated
the scope of anilines for this reaction. The results are summarized
in Table 2. Anilines 1a-1g containing electron-donating groups
on the phenyl ring afforded the corresponding benzothiazoles in
yields ranging from 34% to 81%. Anilines with substituents at
the para and meta-positions provided higher yields than ortho-
substituted anilines, which may be due to the effect of steric
hindrance in the latter case. Substrates with electron-withdrawing
groups at the meta-positions appeared compatible under the
optimal reaction condition with excellent yields (3ah-3aj).
Disappointingly, p-nitro-substituted aniline 1k was not suitable
for this transformation, which indicated that aniline might have
o
b
c
o
d
inherent drawbacks especially in the preparation of starting
materials, which limit their synthetic applications. Recently,
Deng et al. reported a more straightforward approach for the
synthesis of 2-aryl benzothiazoles from amines, sulfur powder
and benzaldehydes, which solved the problems well (Scheme 1,
c).13 Whereas, designing an effective strategy for preparing 2-
aryl benzothiazoles from readily available starting materials
and innocuous solvent in mild condition is still requisite.
Herein, we developed an efficient procedure to synthesize 2-
aryl benzothiazoles from anilines, elemental sulfur, and
acetophenones which are cheap, commercially available and
Table 3. Scope of substituted acetophenones.
relatively stable, with
(Scheme 1, d).
a C(CO)-C(alkyl) bond cleavage
2. Results and discussion
Our initial efforts were focused on the reaction of p-toluidine
1a, acetophenone 2a, and elemental sulfur in the presence of 5
o
equiv Na2SO4 using I2 as a catalyst at 140 C. However, the
desired product 3aa was isolated in only 23% yield and
increasing the amount of iodine ignificantly lowered the yield
(Table 1, entries 1-2). To our delight, the addition of a small
quantity of dimethyl sulfoxide (DMSO) afforded the desired
product in 66% yield (Table 1, entry 3). These results indicated
that the process required only catalytic dose of iodine and that
DMSO catalyzed the oxidation of HI to iodine in the redox
system. Next, various catalyst systems were examined for the
reaction and the I2 (15 mol %)/tetrabutylammonium iodide
TBAI (20 mol%) system was found to be the most efficient
(Table 1, entries 4-8). Further optimization based on solvent
screening showed that PhCl was the most effective solvent for
this reaction (Table 1, entries 9-11). The expected increase in
product yield was not observed when the reactions were carried
o
out at 120 C and 150 oC (entries 12-13). In addition, a much
lower yield was obtained when the reaction was carried out
without anhydrous sodium sulfate, which serves as the drying

3
transformed into dihydro benzothiazole D via intramolecular
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cyclization. The methyl group of intermediate D is iodized to
produce E and intermediate E possibly goes through a SN2
reaction with DMSO to afford F. Intermediate F is oxidized to
the desired product 3 along with the elimination of dimethyl
sulfide and methanal.
Scheme 2. Reaction conditions with respect to 2-aminonaphthalene
experienced a nucleophilic attack.
3. Conclusion
To further examine the scope and limitations of the reaction,
we assessed various acetophenones (Table 3). Acetophenones
with electron-donating groups smoothly reacted with the desired
anilines and sulfur powder, affording the corresponding products
(3ba-3fa). In the intermolecular effect, both para and meta-
positions afforded good yields. In the case of ortho substituted
acetophenone (3da), the yield was poor owing to the large ortho
steric hindrance. Moreover, 2g-2n including halogens such as F,
Cl, Br and electron-withdrawing groups such as -CF3 were
tolerated well in this reaction and the corresponding products
3ga-3na were obtained in reasonable yields of 40%-68%.
In summary, we have developed an I2-catalyzed three-
component reaction for the synthesis of 2-aryl benzothiazoles
from readily available anilines, acetophenones and elemental
sulfur. Our protocol is advantageous in that it does not require
pre-activation of the substrates or rigorous reaction conditions. In
this reaction, the C(CO)−C(alkyl) bond in the acetophenones is
cleaved, leading to the formation of C-N and C-S bonds for the
construction of benzothiazole skeleton. In addition, various
substituted acetophenones and anilines containing 2-
naphthalenamine readily participate in the reaction with
elemental sulfur to furnish the desired products in moderate to
good yields.
To further demonstrate the application of our protocol, we
used 2-naphthalenamine as the substrate for this transformation
(Scheme 2). Gratifyingly, 2-aminonaphthalene was also suitable
for this transformation, and the desired product 2-
phenylnaphtho[2,1-d]thiazole (5aa) was obtained in 66% yield.
2a
NH2
R
1
N
N
R
H2O
R
S
To gain insight into the reaction mechanism, a sequence of
control experiments was performed under the standard conditions,
as shown in Scheme 3. First, when a radical scavenger such as
TEMPO and BHT was added in the reaction, the desired
transformation continued, thereby excluding any possible
mechanism related to the generation of free radicals. Next, we
speculated that 2-aminobenzenethiol or 2-iodoaniline may be a
key intermediate before the cyclization reaction. Therefore, we
conducted the next control experiment in the absence of
acetophenone under standard conditions (Scheme 3, b), which
revealed that aniline does not convert into 6 or 7 at all.
Furthermore, the generation of imine 8 was superior when the
reaction was performed within 1 h (Scheme 3, c). Moreover,
imine 8 could convert into the final benzothiazole under the
standard conditions (Scheme 3, d).
3
A
S
[O]
HCHO
N
H
H
H
R
S
N
O
R
Sn
A'
S
S
O
F
N
S
S
O
S
I
R
H
N
HI
Sn-1
H
R
S
B
I2
Sn-1
H
E
R
N
NH
R
S
Based on our experiments and previous reports,14 a plausible
mechanism for the approach is proposed in Scheme 4. The
reaction is initiated by the condensation of amine and
acetophenone to produce Schiff’s base A. Schiff’s base A can be
converted to a resonance structure A’ at heating condition, which
happens a nucleophilic attack on the elemental sulfur leading to
intermediate B. B is then transformed into C via Sn-1 extrusion
and deprotonation. Subsequently, the active intermediate C is
S
C
D
Scheme 4. Proposed mechanism
4. Experimental section
4.1 General
1H NMR, and 13C NMR spectra were recorded on Bruker
400M and Mercury 300M in CDCl3 or DMSO. All 1H NMR and
13C NMR chemical shifts were given as δ value (ppm) with
reference to tetramethylsilane (TMS) as an internal standard. All
compounds were further characterized by HRMS; copies of their
1H NMR and 13C NMR spectra were provided. Products were
purified by flash chromatography on 200–300 mesh silica gels.
All melting points were determined without correction. All
reagents were purchased commercially and used as received,
unless otherwise noted.
4.2 Procedure for the synthesis of 3aa and 5aa
A mixture of acetophenone (2a, 0.2 mmol), p-toluidine (1a,
0.4 mmol), S8 (0.8 mmol), I2 (15 mol%), TBAI (20 mol%),
DMSO (0.1 mmol) and sodium sulfate (1 mmol) in PhCl (0.6 mL)
Scheme 3. Control experiments.

4
Tetrahedron
o
was stirred at 140 C for 48 h. After the reaction mixture was
1H), 7.48 – 7.40 (m, 3H), 7.30 (dd, J = 8.4, 1.2 Hz, 1H), 2.74 (q,
J = 7.6 Hz, 2H), 1.27 (t, J = 7.6 Hz, 3H). 13C NMR (75 MHz,
CDCl3) δ 166.9, 152.3, 141.6, 135.1, 133.6, 130.6, 128.8, 127.3,
126.7, 122.7, 120.1, 28.8, 15.8. HRMS (ESI): m/z calcd for
C15H14NS (M+H)+ 240.0842; found: 240.0847.
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cooled to room temperature, the solvent was removed under
reduced pressure to obtain the crude product. The residue was
purified by silica gel chromatography (eluent: petroleum/ethyl
acetate = 40/1) to obtain the desired product 3aa as white solid.
A
mixture of acetophenone (2a, 0.2 mmol), 2-
4.3.7. 6-methoxy-2-phenylbenzo[d]thiazole (3ag)
aminonaphthalene (4a, 0.24 mmol), S8 (0.6 mmol), and I2 (20
mol%) in NMP (1 mL) was stirred at 140 C for 48 h. After the
Compound 3ag was isolated as a white solid (64% yield, 30.7
mg, mp: 118-120 oC). 1H NMR (300 MHz, CDCl3) δ 8.08 – 7.89
(m, 3H), 7.51 – 7.39 (m, 3H), 7.30 (d, J = 2.3 Hz, 1H), 7.07 (dd,
J = 8.9, 2.4 Hz, 1H), 3.84 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
165.4, 157.6, 148.5, 136.3, 133.6, 130.4, 128.9, 127.1, 123.6,
115.6, 103.9, 55.7. HRMS (ESI): m/z calcd for C14H12NOS
(M+H)+ 242.0634; found: 242.0630.
o
reaction mixture was cooled to room temperature, the solvent
was removed under reduced pressure to obtain the crude product.
The residue was purified by silica gel chromatography (eluent:
petroleum/ethyl acetate = 10/1) to obtain the desired product 5aa
as light yellow solid.
4.3 Compound data of products 3 and 5aa
4.3.1. 6-methyl-2-phenylbenzo[d]thiazole (3aa)
4.3.8. 5-fluoro-2-phenylbenzo[d]thiazole (3ah)
Compound 3ah was isolated as a light yellow solid (62% yield,
o
1
Compound 3aa was isolated as a white solid (81% yield, 36.4
mg, mp: 121-123 oC). 1H NMR (400 MHz, ) δ 8.07 (ddd, J = 6.2,
1.9, 0.6 Hz, 2H), 7.95 (d, J = 8.3 Hz, 1H), 7.68 (d, J = 0.6 Hz,
1H), 7.51 – 7.45 (m, 3H), 7.30 (d, J = 8.2 Hz, 1H), 2.49 (s, 3H).
13C NMR (75 MHz, CDCl3) δ 166.9, 152.2, 135.3, 135.1, 133.6,
130.7, 128.9, 127.8, 127.3, 122.6, 121.3, 21.5. HRMS (ESI): m/z
calcd for C14H12NS (M+H)+ 226.0685; found: 226.0690.
28.4 mg, mp: 119-121 C). H NMR (300 MHz, CDCl3) δ 8.07
(dd, J = 6.7, 3.0 Hz, 2H), 7.82 (dd, J = 8.8, 5.1 Hz, 1H), 7.75 (dd,
J = 9.5, 2.5 Hz, 1H), 7.51 (dd, J = 6.4, 3.9 Hz, 3H), 7.16 (td, J =
8.8, 2.5 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 170.5, 163.5-
160.3 (d, J = 241.5 Hz, 1C), 155.0-154.9 (d, J = 12.0 Hz, 1C),
133.3, 131.3, 130.3, 129.1, 127.5, 122.3-122.2 (d, J = 9.8 Hz, 1C),
114.0-113.7 (d, J = 24.8 Hz, 1C), 109.5-109.2 (d, J = 23.3 Hz,
1C). HRMS (ESI): m/z calcd for C13H9FNS (M+H)+ 230.0434;
found: 230.0438.
4.3.2. 2-phenylbenzo[d]thiazole (3ab)
Compound 3ab was isolated as a white solid (70% yield, 29.5
mg, mp: 114-117 oC). 1H NMR (300 MHz, CDCl3) δ 8.13 – 8.03
(m, 3H), 7.88 (d, J = 7.9 Hz, 1H), 7.53 – 7.42 (m, 4H), 7.42 –
7.32 (m, 1H). 13C NMR (75 MHz, CDCl3) δ 167.9, 154.1, 134.9,
133.5, 130.8, 128.9, 127.5, 126.2, 125.1, 123.1, 121.5. HRMS
(ESI): m/z calcd for C13H10NS (M+H)+ 212.0529; found:
212.0533.
4.3.9. 5-chloro-2-phenylbenzo[d]thiazole (3ai)
Compound 3ai was isolated as a light yellow solid (79% yield,
38.6 mg, mp: 138-141 oC). 1H NMR (300 MHz, CDCl3) δ 8.09 –
8.03 (m, 3H), 7.79 (d, J = 8.5 Hz, 1H), 7.53 – 7.47 (m, 3H), 7.35
(dd, J = 8.5, 2.0 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 169.9,
154.9, 133.2, 133.1, 132.2, 131.3, 129.1, 127.5, 125.6, 122.9,
122.3. HRM (ESI): m/z calcd for C13H9ClNS (M+H)+ 246.0139;
found: 246.0142.
4.3.3. 5-methyl-2-phenylbenzo[d]thiazole (3ac)
Compound 3ac was isolated as a yellow solid (59% yield,
26.5 mg, mp: 140-142 oC). 1H NMR (300 MHz, CDCl3) δ 8.12 –
8.04 (m, 2H), 7.90 – 7.86 (m, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.52
– 7.44 (m, 3H), 7.24 – 7.18 (m, 1H), 2.51 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 168.1, 154.4, 136.3, 133.7, 131.9, 130.8, 128.9,
127.4, 126.8, 123.2, 121.0, 21.4. HRMS (ESI): m/z calcd for
C14H12NS (M+H)+ 226.0685; found: 226.0680.
4.3.10. 5-bromo-2-phenylbenzo[d]thiazole (3aj)
Compound 3aj was isolated as a light yellow solid (71% yield,
o
1
40.9 mg, mp: 134-137 C). H NMR (400 MHz, CDCl3 ) δ 8.20
(d, J = 1.8 Hz, 1H), 8.05 (dt, J = 5.3, 2.0 Hz, 2H), 7.72 (d, J = 8.4
Hz, 1H), 7.51 – 7.45 (m, 4H). 13C NMR (100 MHz, CDCl3) δ
169.6, 155.2, 133.8, 133.1, 131.3, 129.1, 128.2, 127.6, 126.0,
122.6, 119.8. HRMS (ESI): m/z calcd for C13H9BrNS (M+H)+
289.9634; found: 289.9635.
4.3.4. 4-methyl-2-phenylbenzo[d]thiazole (3ad)
Compound 3ad was isolated as a yellow liquid (34% yield,
15.3 mg). H NMR (300 MHz, CDCl3) δ 8.14 – 8.07 (m, 2H),
4.3.11. 6-methyl-2-(p-tolyl)benzo[d]thiazole(3ba)
1
7.74 – 7.68 (m, 1H), 7.50 – 7.44 (m, 3H), 7.29 – 7.24 (m, 2H),
2.81 (d, J = 0.8 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 166.5,
153.5, 135.0, 133.9, 133.3, 130.6, 128.9, 127.5, 126.7, 125.0,
118.9, 18.3. HRMS (ESI): m/z calcd for C14H12NS (M+H)+
226.0685; found, 226.0689.
Compound 3ba was isolated as a white solid (70% yield, 33.4
mg, mp: 144-147 oC). 1H NMR (300 MHz, CDCl3) δ 7.97 – 7.89
(m, 3H), 7.60 (d, J = 0.7 Hz, 1H), 7.29 – 7.21 (m, 3H), 2.44 (s,
3H), 2.38 (s, 3H).13C NMR (75 MHz, CDCl3) δ 167.1, 152.1,
141.0, 134.9, 134.9, 130.9, 129.5, 127.7, 127.2, 122.4, 121.2,
21.5, 21.4. HRMS (ESI): m/z calcd for C15H14NS (M+H)+
240.0842; found: 240.0845.
4.3.5. 4,5-dimethyl-2-phenylbenzo[d]thiazole (3ae)
Compound 3ae was isolated as a white solid (45% yield, 21.5
4.3.12. 6-methyl-2-(m-tolyl)benzo[d]thiazole(3ca)
o
1
mg, mp: 77-79 C). H NMR (300 MHz, CDCl3) δ 8.09 (dd, J =
6.5, 3.1 Hz, 2H), 7.59 (d, J = 8.1 Hz, 1H), 7.51 – 7.42 (m, 3H),
7.17 (d, J = 8.1 Hz, 1H), 2.74 (s, 3H), 2.40 (s, 3H). 13C NMR (75
MHz, CDCl3) δ 166.3, 153.9, 134.1, 132.3, 131.5, 130.5, 128.9,
127.4, 127.3, 118.1, 19.6, 14.9. HRMS (ESI): m/z calcd for
C15H14NS (M+H)+ 240.0842; found: 240.0840.
Compound 3ca was isolated as a white solid (78% yield, 37.2
mg, mp: 72-75 oC). 1H NMR (300 MHz, CDCl3) δ 7.77 – 7.68 (m,
2H), 7.61 (dd, J = 7.6, 0.5 Hz, 1H), 7.40 (d, J = 0.7 Hz, 1H), 7.13
(t, J = 7.6 Hz, 1H), 7.08 – 7.01 (m, 2H), 2.24 (s, 3H), 2.21 (s,
3H).13C NMR (75 MHz, CDCl3) δ 167.1, 152.0, 138.6, 135.1,
134.9, 133.4, 131.4, 128.7, 127.7, 127.7, 124.6, 122.5, 121.2,
21.4, 21.2. HRMS (ESI): m/z calcd for C15H14NS (M+H)+
240.0842; found: 240.0828.
4.3.6. 6-ethyl-2-phenylbenzo[d]thiazole (3af)
Compound 3af was isolated as a yellow solid (72% yield, 34.4
o
1
mg, mp: 39-42 C). H NMR (300 MHz, CDCl3) δ 8.05 (dd, J =
6.6, 2.9 Hz, 2H), 7.97 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 0.8 Hz,
4.3.13. 6-methyl-2-(o-tolyl)benzo[d]thiazole (3da)

5
Compound 3da was isolated as a light yellow solid (49% yield,
125.5, 122.8, 121.3, 21.5. HRMS (ESI): m/z calcd for
C14H11ClNS (M+H)+ 260.0295; found: 260.0296.
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23.4 mg, mp: 35-37 oC).1H NMR (400 MHz, CDCl3) δ 7.97 (d, J
= 8.3 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.69 (s, 1H), 7.37 – 7.25
(m, 4H), 2.64 (s, 3H), 2.49 (s, 3H). 13C NMR (75 MHz, CDCl3) δ
166.7, 151.7, 136.9, 135.5, 134.9, 132.9, 131.3, 130.3, 129.6,
127.5, 125.9, 122.6, 120.9, 21.4, 21.3. HRMS (ESI): m/z calcd
for C15H14NS (M+H)+ 240.0842; found: 240.0841.
4.3.20. 2-(2-chlorophenyl)-6-methylbenzo[d]thiazole (3ka)
Compound 3ka was isolated as a light yellow solid (40% yield,
20.7 mg, mp: 102-105 oC). 1H NMR (300 MHz, CDCl3) δ 8.22 –
8.15 (m, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.67 (s, 1H), 7.52 – 7.44
(m, 1H), 7.39 – 7.26 (m, 3H), 2.47 (s, 3H). 13C NMR (75 MHz,
CDCl3) δ 162.9, 150.5, 136.1, 135.5, 132.4, 132.2, 131.5, 130.8,
130.6, 127.8, 126.9, 122.8, 120.9, 21.5. HRMS (ESI): m/z calcd
for C14H11ClNS (M+H)+ 260.0295; found: 260.0294.
4.3.14. 2-(4-isopropylphenyl)-6-methylbenzo[d]thiazole (3ea)
Compound 3ea was isolated as a light yellow solid (72% yield,
o
1
38.4 mg, mp: 98-101 C). H NMR (300 MHz, CDCl3) δ 8.02 –
7.96 (m, 2H), 7.93 (d, J = 8.3 Hz, 1H), 7.66 (s, 1H), 7.33 (d, J =
8.4 Hz, 2H), 7.28 (dd, J = 8.3, 1.6 Hz, 1H), 2.97 (m, 1H), 2.48 (s,
3H), 1.29 (d, J = 6.9 Hz, 6H). 13C NMR (75 MHz, CDCl3) δ
167.1, 152.2, 151.9, 135.1, 131.4, 127.8, 127.4, 127.0, 122.5,
121.3, 109.7, 34.1, 23.8, 21.5. HRMS (ESI): m/z calcd for
C17H18NS (M+H)+ 268.1155; found: 268.1157.
4.3.21. 2-(4-bromophenyl)-6-methylbenzo[d]thiazole (3la)
Compound 3la was isolated as a white solid (62% yield, 37.4
mg, mp: 199-202 oC). 1H NMR (300 MHz, CDCl3) δ 7.96 – 7.90
(m, 3H), 7.69 (s, 1H), 7.64 – 7.59 (m, 2H), 7.31 (dd, J = 8.4, 1.5
Hz, 1H), 2.50 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.6, 152.1,
135.7, 135.1, 132.6, 132.1, 128.7, 128.1, 125.1, 122.7, 121.4,
21.6. HRMS (ESI): m/z calcd for C14H11BrNS (M+H)+ 303.9790;
found: 303.9795.
4.3.15. 2-(4-methoxyphenyl)-6-methylbenzo[d]thiazole (3fa)
Compound 3fa was isolated as a light yellow solid (30% yield,
15.3 mg, mp: 170-173 oC). 1H NMR (400 MHz, CDCl3) δ 8.05 –
7.98 (m, 2H), 7.90 (d, J = 8.3 Hz, 1H), 7.66 (s, 1H), 7.28 (d, J =
9.5 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 2.49 (s, 3H).
13C NMR (100 MHz, CDCl3) δ 166.8, 161.7, 152.3, 134.9, 134.9,
128.9, 127.8, 126.5, 122.3, 121.3, 114.3, 55.4, 21.5. HRMS (ESI):
m/z calcd for C15H14NOS (M+H)+ 256.0791; found: 256.0789.
4.3.22. 2-(3-bromophenyl)-6-methylbenzo[d]thiazole (3ma)
Compound 3ma was isolated as a white solid (65% yield, 39.2
mg, mp: 119-121 oC). H NMR (300 MHz, CDCl3) δ 8.21 (t, J =
1
1.8 Hz, 1H), 7.89 (ddd, J = 4.1, 3.3, 2.6 Hz, 2H), 7.63 – 7.58 (m,
1H), 7.54 (ddd, J = 8.0, 1.9, 1.0 Hz, 1H), 7.32 – 7.23 (m, 2H),
2.45 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 164.9, 151.9, 135.7,
135.4, 135.1, 133.4, 130.3, 129.9, 128.0, 125.8, 123.0, 122.7,
121.3, 21.5. HRMS (ESI): m/z calcd for C14H11BrNS (M+H)+
303.9790; found: 303.9786.
4.3.16. 2-(4-fluorophenyl)-6-methylbenzo[d]thiazole (3ga)
Compound 3ga was isolated as a white solid (61% yield, 29.6
mg, mp: 160-162 oC). 1H NMR (300 MHz, CDCl3) δ 8.07 – 7.99
(m, 2H), 7.92 (d, J = 8.3 Hz, 1H), 7.65 – 7.62 (m, 1H), 7.28 (ddd,
J = 8.3, 1.1, 0.6 Hz, 1H), 7.19 – 7.10 (m, 2H), 2.47 (s, 3H). 13C
NMR (75 MHz, CDCl3) δ 165.9 – 165.6 (d, J = 21.8 Hz, 1C),
162.6, 152.1, 135.4, 135.1, 130.0 – 129.9 (d, J = 3.0 Hz, 1C),
129.3 – 129.2 (d, J = 8.3 Hz, 1C), 127.9, 122.6, 121.3, 116.2 –
4.3.23. 6-methyl-2-(4-(trifluoromethyl)phenyl)benzo[d]thiazole
(3na)
Compound 3na was isolated as a white solid (68% yield, 39.8
o
1
mg, mp: 94-97 C). H NMR (300 MHz, CDCl3) δ 8.18 (d, J =
8.6 Hz, 2H), 7.97 (d, J = 8.4 Hz, 1H), 7.77 – 7.69 (m, 3H), 7.33
(dd, J = 8.4, 1.6 Hz, 1H), 2.51 (s, 3H). 13C NMR (75 MHz,
CDCl3) δ 164.9, 152.1, 136.9, 136.1, 135.4, 132.4, 132.0, 128.3,
127.6, 126.0 – 125.9 (q, J = 3.8 Hz, 1C), 123.1, 121.4, 21.6.
HRMS (ESI): m/z calcd for C15H11F3NS (M+H)+ 294.0559;
found: 294.0562.
115.9 (d,
J = 22.5 Hz, 1C), 21.5. HRMS (ESI): m/z
calcd for C14H11FNS (M+H)+ 244.0591; found: 244.0594.
4.3.17. 2-(3-fluorophenyl)-6-methylbenzo[d]thiazole (3ha)
Compound 3ha was isolated as a white solid (65% yield, 31.5
mg, mp: 96-99 oC). 1HNMR (300 MHz, CDCl3) δ 7.91 (d, J = 8.3
Hz, 1H), 7.79 – 7.72 (m, 2H), 7.58 (s, 1H), 7.38 (td, J = 8.2, 5.8
Hz, 1H), 7.28 – 7.22 (m, 1H), 7.16 – 7.08 (m, 1H), 2.43 (s, 3H).
13C NMR (75 MHz, CDCl3): δ 165.2, 164.5 – 161.2 (d, J = 245.3
Hz, 1C), 151.9, 135.7, 135.6, 135.0, 130.5 – 130.4 (d, J = 7.5 Hz,
1C), 127.9, 123.0, 122.9 – 122.7 (d, J = 18.0 Hz, 1C), 121.2,
117.6 – 117.3 (d, J = 21.0 Hz, 1C), 114.1 – 113.8 (d, J = 23.3 Hz,
1C), 21.5. HRMS (ESI): m/z calcd for C14H11FNS (M+H)+
244.0591; found: 244.0594.
4.3.24. 2-Phenylnaphtho[2,1-d]thiazole (5aa)
Compound 5aa was isolated as a light yellow solid (66% yield,
34.4 mg, mp: 102-105 oC). 1H NMR (300 MHz, CDCl3) δ 8.21 –
8.01 (m, 3H), 7.94 (dd, J = 16.9, 7.6 Hz, 2H), 7.83 (d, J = 8.8 Hz,
1H), 7.60 – 7.26 (m, 5H). 13C NMR (75 MHz, CDCl3) δ 167.1,
152.1, 133.6, 132.1, 130.9, 130.7, 128.9, 128.9, 127.9, 127.3,
127.2, 126.9, 125.9, 125.1, 121.6. HRMS (ESI): m/z calcd for
C17H12NS (M+H)+ 262.0685; found, 262.0689.
4.3.18. 2-(4-chlorophenyl)-6-methylbenzo[d]thiazole (3ia)
Compound 3ia was isolated as a light yellow solid (58% yield,
30.0 mg, mp: 182-187 oC). 1H NMR (300 MHz, CDCl3) δ 8.04 –
7.98 (m, 2H), 7.94 (d, J = 8.4 Hz, 1H), 7.69 (s, 1H), 7.49 – 7.43
(m, 2H), 7.31 (dd, J = 8.3, 1.2 Hz, 1H), 2.50 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ 165.5, 152.1, 136.7, 135.6, 135.1, 132.2,
129.2, 128.5, 128.1, 122.7, 121.4, 21.6. HRMS (ESI): m/z calcd
for C14H11ClNS (M+H)+ 260.0295; found: 260.0291.
Acknowledgments
We are grateful for the sponsorship by the National Natural
Science Foundation of China (Nos. 21372102) for this project. 1H
NMR and 13C NMR spectra were determined on 300 MHz and 75
MHz in CDCl3. Unknown products were further characterized by
HRMS (TOF-ESI), the melting points of solid products were
determined on a microscopic apparatus.
4.3.19. 2-(3-chlorophenyl)-6-methylbenzo[d]thiazole (3ja)
Compound 3ja was isolated as a yellow solid (67% yield, 34.7
mg, mp: 115-119 oC). 1H NMR (300 MHz, CDCl3) δ 8.09 (s, 1H),
7.97 – 7.88 (m, 2H), 7.68 (s, 1H), 7.46 – 7.36 (m, 2H), 7.31 (d, J
= 8.3 Hz, 1H), 2.49 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 165.1,
151.9, 135.7, 135.3, 135.1, 134.9, 130.5, 130.1, 128.1, 127.1,
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