Silver-mediated 2-arylation/alkylation/acylation of benzothiazoles with aldehydes in water

Article abstract of DOI:10.3987/COM-18-13934

An efficient and environmentally benign method was developed for the facile synthesis of various 2-aryl and 2-alkyl substituted benzothiazoles in moderate to good yields, using a silver-mediated redox condensation of benzothiazoles and aldehydes in water. Furthermore, this method is also applicable to prepare 2-acyl benzothiazoles.

Full text of DOI:10.3987/COM-18-13934

1226
HETEROCYCLES, Vol. 96, No. 7, 2018
HETEROCYCLES, Vol. 96, No. 7, 2018, pp. 1226 - 1237. © 2018 The Japan Institute of Heterocyclic Chemistry
Received, 6th June, 2018, Accepted, 21st June, 2018, Published online, 28th June, 2018
DOI: 10.3987/COM-18-13934
SILVER-MEDIATED 2-ARYLATION/ALKYLATION/ACYLATION OF
BENZOTHIAZOLES WITH ALDEHYDES IN WATER
Min Hua, Chunqin Wang, Qixing Liu,* Danyi Chen, Hao Fu, and Haifeng
Zhou*
Research Center of Green Pharmaceutical Technology and Process, Hubei Key
Laboratory of Natural Products Research and Development, College of Biological
and Pharmaceutical Sciences, China Three Gorges University, Yichang 443002,
China. E-mail: qixingliu86@163.com (Qixing Liu); zhouhf@ctgu.edu.cn (Haifeng
Zhou)
Abstract – An efficient and environmentally benign method was developed for
the facile synthesis of various 2-aryl and 2-alkyl substituted benzothiazoles in
moderate to good yields, using a silver-mediated redox condensation of
benzothiazoles and aldehydes in water. Furthermore, this method is also
applicable to prepare 2-acyl benzothiazoles.
INTRODUCTION
2-Substituted benzothiazoles are important building blocks of pharmaceuticals and natural products.1 For
instance, the antitumor and anti-hepatitis C virus (anti-HCV) drug molecules contain benzothiazole
moieties (Scheme 1).2 Therefore, the development of efficient methods for the synthesis of 2-substituted
benzothiazoles and its analogues has drawn much attention.
Scheme 1. Some Drugs Contain 2-Substituted Benzothiazole

HETEROCYCLES, Vol. 96, No. 7, 2018
1227
To date, some synthetic routes have been developed for the preparation of 2-substituted benzothiazoles. It
can be divided into three broad categories: (1) the condensation of 2-aminothiophenols with aryl
aldehydes, carboxylic acids, nitriles, acyl chlorides, or alcohols;3 (2) transition metal-catalyzed direct
C–H activation and C–C coupling of benzothiazole with aryl halides, arylboronic acids,
iodobenzenediacetate, arenediazonium salts, aryl sulfamates, aryltrimethylammonium triflates, arene
benzenesulfonyl chlorides, substituted benzoic acids, or triarylbismuth reagents;4 (3) redox condensation
of benzothiazoles with aldehydes, benzylic alcohols, and styrenes.5 However, there are some drawbacks
in the above methods. For example, the expensive and unstable 2-aminothiophenol was used as starting
materials; expensive transition metal was used as catalysts. To continue our interest in silver catalysis,6
we report herein a silver-mediated redox condensation of benzothiazoles with aromatic and aliphatic
aldehydes, as well as phenylglyoxal in water, affording a variety of 2-aryl, 2-alkyl, and 2-acyl substituted
benzothiazoles in high yields.
RESULTS AND DISCUSSION
Initially, the redox condensation of benzothiazole (1a) and benzaldehyde (2a) in AcOH-H2O (8:2) at
100 °C for 24 h under air was chosen as a model reaction. As shown in Table 1, the different oxidants
such as AgOTf, AgNO3, Ag2CO3, AgOTs, DTBP, Cu(OAc)2, and O2 were investigated (entries 1–7). And
the highest yield of 3a (88%) was obtained using AgOTs as an oxidant. However, the yield of 3a was
decreased with the decrease of the amount of oxidant (entries 8–9). Interestingly, up to 90% yield was
obtained when the reaction was performed under nitrogen atmosphere (entry 10). It maybe ascribe to the
oxidation of the benzaldehyde to benzoic acid under air.7 It was found that there is no effect on the yield
even if shortening the reaction time to 12 h (entries 10–12). Next, the ratio of AcOH and H2O was
examined (entries 13–15). An 81% yield of 3a was obtained in an equal volume of AcOH and H2O (entry
13). To our delight, 3a was isolated with 95% yield in H2O (entry 15). And then, the reaction was also
conducted at lower temperature, but the yield decreased apparently (entries 16–17). The structure of 3a
1
13
was determined not only by H NMR, C NMR, and HRMS, but also by single crystal X-ray analysis
(CCDC 1814089).
With the optimized reaction conditions in hand, the substrate scope was investigated. As shown in
Scheme 2, the reaction of benzothiazole (1a) with both electron-poor and electron-rich aromatic
aldehydes was conducted smoothly, giving the corresponding products 3b–3n in 46–95% yield. Notably,
the aldehydes bearing a free hydroxyl group or methylal moiety were also tolerated, providing the desired
products 3m and 3n in 46% and 63% yields, respectively. In addition, the 1-naphthaldehyde (2o) and
furan-2-carbaldehyde (2p) were also applicable to this reaction, and the desired benzothiazoles 3o and 3p
were obtained in 87% and 79% yields, respectively. To our delighted, the aliphatic aldehydes like

1228
HETEROCYCLES, Vol. 96, No. 7, 2018
Table 1. Optimization of the Reaction Conditionsa
CHO
S
N
S
N
+
1a
2a
3a
Entry
1
Oxidant (equiv)
AgOTf (2)
AgNO3 (2)
Ag2CO3 (2)
AgOTs (2)
DTBP (2)
Solvent (V:V)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (8:2)
ACOH-H2O (5:5)
ACOH
T (°C)
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
90
t (h)
24
24
24
24
24
24
24
24
24
24
12
9
Yield (%)b
64
12
33
88
12
20
9
2
3
4
5
6
Cu(OAc)2 (2)
O2 (1atm)
7
8
AgOTs (1.5)
AgOTs (1)
AgOTs (2)
AgOTs (2)
AgOTs (2)
AgOTs (2)
AgOTs (2)
AgOTs (2)
AgOTs (2)
AgOTs (2)
77
46
90
90
86
81
17
95
72
52
9
10c
11c
12c
13c
14c
15c
16c
17c
12
12
12
12
12
H2O
H2O
H2O
80
aReaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), oxidant, solvent (2 mL), under air. DTBP: di-t-butyl
peroxide. bIsolated yield. cUnder nitrogen atmosphere.
cyclohexanecarbaldehyde (2q), cyclopentanecarbaldehyde (2r), cyclopropanecarbaldehyde (2s),
isobutyraldehyde (2t), 2-methylbutanal (2u), as well as 2-phenylpropanal (2v) are also applicable, and the
corresponding products 3q–3v were obtained in 64–85% yield. Subsequently, the scope of benzothiazoles
was also examined. For example, the electron-poor 6-bromobenzothiazole and electron-rich
6-methoxybenzothiazole gave the desired product 3w and 3x in 85% and 69% yields, respectively.
Aryl heteroaryl ketones are important skeletons of pharmaceuticals, such as diflumidone, raloxifene and
tiaprofenic acid.8 Liu and Wang reported the redox condensation of benzothiazoles with phenylglyoxal,
and 2-benzoylbenzothiazole was obtained with only 31% and 44% yields.9 To further demonstrate the
scope of this methodology, the phenylglyoxal 4a and methylglyoxal 4b were also subjected to the

HETEROCYCLES, Vol. 96, No. 7, 2018
1229
reaction with benzothiazoles (Scheme 3). To our delighted, the corresponding 2-benzoylbenzothiazoles
5a–5c and 2-acetylbenzothiazole 5d were obtained in 69–90% yields.
S
N
S
N
AgOTs (2 equiv)
R-CHO
+
R
R'
R'
H2O
100 oC, 12 h, N2
1
2
3
S
N
S
N
S
S
N
S
N
Me
Br
CN
CF3
N
3a
95%
3b
84%
3c
55%
3d
49%
3e
82%
Me
Br
S
Br
S
N
S
N
S
S
OMe
N
N
N
3f
3g
3h
3i
3j
58%
88%
89%
77%
94%
OMe
OMe
O2N
Me
S
N
S
N
S
S
N
S
OH
OMe
O
N
N
O
3k
3l
3m
3n
3o
98%
50%
46%
63%
87%
Me
Me
S
S
S
S
O
S
N
N
N
N
N
3p
3q
3r
3s
3t
79%
78%
70%
64%
85%
Br
MeO
Me
S
N
S
N
S
N
S
N
Me
Me
3u
3v
3w
3x
83%
68%
85%
69%
Scheme 2. Substrate scope. Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), AgOTs (2 equiv), H2O (2
mL), 12 h, 100 °C, under N2 atmosphere, isolated yield.
O
O
R
S
N
S
N
AgOTs (2 equiv)
+
R'
R'
R
CHO
H2O
100 oC, 12 h, N2
1
4
5
O
O
O
O
N
N
N
N
S
S
S
S
MeO
O2N
5a
90%
5b
75%
5c
69%
5d
81%
Scheme 3. Synthesis of 2-Acylbenzothiazoles. Reaction conditions: 1 (0.5 mmol), 4 (0.6 mmol), AgOTs
(2 equiv), H2O (2 mL), 12 h, 100 °C, under N2 atmosphere, isolated yield.

1230
HETEROCYCLES, Vol. 96, No. 7, 2018
To understand the reaction pathway, several control experiments were performed. As shown in Scheme 4,
under the standard conditions, the benzaldehyde remained intact (eq. 1), whereas benzothiazole was
completely consumed to give 2-aminothiophenol quantitatively (eq. 2). The reaction of benzaldehyde and
2-amino thiophenol proceeded smoothly to give the desired product in 95% yield (eq. 3).
CHO
standard conditions
standard conditions
no reaction
SH
(1)
(2)
S
N
NH2
SH
CHO
S
standard conditions
(3)
+
N
NH2
95% yield
Scheme 4. Control Experiments. Standard conditions: AgOTs (2 equiv), H2O (2 mL), 12 h, 100 °C, under
N2 atmosphere.
Based on the results of control experiments and previous reports,5b,5c,5f,10 a possible reaction pathway was
proposed as shown in Scheme 5. Initially, the benzothiazole (1a) will be opened to give
2-aminobenzenethiol I by silver salt. And then, the condensation of intermediate I with benzaldehyde (2a)
will generate imine II. Next, the intramolecular cyclization of imine II will produce III, followed by
oxidation to give the desired product 3a.
CHO
SH
2a
SH
S
N
S
N
S
Ag(I)
Ag(I)
N
N
H
NH2
1a
I
II
3a
III
Scheme 5. A Possible Reaction Pathway
In summary, we have developed an efficient method for the synthesis of 2-aryl, 2-aklyl, and 2-acyl-
benzothiazoles from readily availably benzothiazoles and corresponding aldehydes in the presence of
silver salt with water as green solvent. Further studies on the detail mechanism and the scope of other
heteroaromatics like benzoimidazoles, benzoxazoles are underway in our laboratory.
EXPERIMENTAL
Unless otherwise noted, all the reagents, catalysts and solvents were purchased from commercial
suppliers and used without further purification. Column Chromatography was performed with silica gel

HETEROCYCLES, Vol. 96, No. 7, 2018
1231
(200–300 mesh). NMR spectra were recorded on Bruker AVANCE III (400 MHz) spectrometers. CDCl3
was used as solvent for the NMR analysis with tetramethylsilane as the internal standard. Chemical shifts
1
13
were reported upfield to TMS (0.00 ppm) for H NMR and relative to CDCl3 (77.0 ppm) for C NMR.
HRMS spectra were acquired using an Agilent 6210 ESI/TOF mass spectrometer. Compounds 3a were
collected at 100 K on a Rigaku Oxford Diffraction Supernova Dual Source, Cu at Zero equipped with an
AtlasS2 CCD using Cu Kα radiation.
General procedure for the synthesis of products
A sealed pressure vessel was charged with benzothiazole (68 mg, 0.5 mmol), AgOTs (280 mg, 1 mmol),
aldehyde (0.6 mmol) and 2.0 mL of H2O. The resulting solution was stirred at 100 ºC for 12 h under N2.
Upon completion of the reaction, H2O (8.0 mL) was added, then extracted with EtOAc (5 mL × 3), dried
over Na2SO4, and concentrated under reduced pressure. The residue was further purified with flash
column chromatography.
2-Phenylbenzothiazole (3a) (CAS No.: 883-93-2)
Following general procedure gave product 3a as a white solid. 95% yield; mp 111–113 °C; 1H NMR (400
MHz, CDCl3) δ 8.16-8.11 (m, 3H), 7.96 (d, J = 7.6 Hz, 1H), 7.57-7.52 (m, 4H), 7.44 (td, J1 = 7.6 Hz, J2 =
1.2 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 168.1, 154.2, 135.1, 133.7, 131.0, 129.0, 127.6, 126.3,
125.2, 123.3, 121.6 ppm; HRMS (ESI) m/z [M + H]+ calcd for C13H10NS 212.0528, found 212.0526.
2-(4-Bromophenyl)benzothiazole (3b) (CAS No.: 19654-19-4)
Following general procedure gave product 3b as a white solid. 84% yield; mp 132–134 ºC. 1H NMR (400
MHz, CDCl3) δ 8.12 (d, J = 8.0 Hz, 1H), 8.02 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 2H), 7.95 (d, J = 8.0 Hz, 1H),
7.67 (dd, J1 = 8.4 Hz, J2 = 2.0 Hz, 2H), 7.55 (t, J = 7.6 Hz, 1H), 7.45 (t, J = 7.6 Hz, 1H) ppm; 13C NMR
(100 MHz, CDCl3) δ 166.7, 154.1, 135.1, 132.6, 132.3, 128.9, 126.5, 125.5, 125.4, 123.3, 121.7 ppm.
2-(4-Cyanophenyl)benzothiazole (3c) (CAS No.: 17930-02-8)
Following general procedure gave product 3c as a white solid. 55% yield; mp 165–166 ºC; 1H NMR (400
MHz, CDCl3) δ 8.26 (d, J = 8.4 Hz, 2H), 8.16 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.84 (d, J =
8.4 Hz, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 165.4,
154.0, 137.5, 135.3, 132.8, 128.0, 126.9, 126.1, 123.8, 121.8, 118.3, 114.2 ppm.
2-(4-Trifluoromethylphenyl)benzothiazole (3d) (CAS No.: 134384-31-9)
Following general procedure gave product 3d as a white solid. 49% yield; mp 159–161 ºC; 1H NMR (400
MHz, CDCl3) δ 8.26 (d, J = 8.0 Hz, 2H), 8.16 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.81 (d, J =
8.4 Hz, 2H), 7.58 (t, J = 7.6 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ 166.1,
154.1, 136.8, 135.2, 132.7, 132.3, 127.8, 126.7, 126.0 (m), 123.7, 122.5, 121.8 ppm.
2-(4-Methylphenyl)benzothiazole (3e) (CAS No.: 16112-21-3)
1
Following general procedure gave product 3e as a white solid. 82% yield; mp 85–86 ºC; H NMR (400

1232
HETEROCYCLES, Vol. 96, No. 7, 2018
MHz, CDCl3) δ 8.11 (d, J = 8.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 7.6 Hz, 1H), 7.53 (td, J1 =
7.6 Hz, J2 = 1.2 Hz, 1H), 7.42 (td, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 2.47 (s, 3H)
ppm; 13C NMR (100 MHz, CDCl3) δ 168.3, 154.2, 141.5, 135.0, 131.0, 129.7, 127.5, 126.3, 125.0, 123.1,
121.6, 21.6 ppm.
2-(4-(tert-Butyl)phenyl)benzothiazole (3f) (CAS No.: 56048-52-3)
1
Following general procedure gave product 3f as a red solid. 58% yield; mp 108–109 ºC; H NMR (400
MHz, CDCl3) δ 8.12 (d, J = 8.4 Hz, 1H), 8.08 (d, J = 8.4 Hz, 2H), 7.95 (d, J = 8.0 Hz, 1H), 7.57 (d, J =
13
8.4 Hz, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 1.42 (s, 9H) ppm; C NMR (100 MHz,
CDCl3) δ 168.2, 154.6, 154.2, 135.0, 130.9, 127.4, 126.2, 126.0, 125.0, 123.1, 121.6, 35.0, 31.2 ppm.
2-(4-Methoxyphenyl)benzothiazole (3g) (CAS No.: 6265-92-5)
Following general procedure gave product 3g as a green solid. 88% yield; mp 123–124 ºC; 1H NMR (400
MHz, CDCl3) δ 8.09 (d, J = 8.4 Hz, 3H), 7.93 (d, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.40 (t, J = 7.6
Hz, 1H), 7.05 (d, J = 8.4 Hz, 2H), 3.93 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 167.9, 162.0, 154.2,
134.9, 129.2, 126.4, 126.2, 124.8, 122.9, 121.5, 114.4, 55.5 ppm.
2-(2-Bromophenyl)benzothiazole (3h) (CAS No.: 22901-00-4)
Following general procedure gave product 3h as a yellow solid. 89% yield; mp 68–69 ºC; 1H NMR (400
MHz, CDCl3) δ 8.20 (d, J = 8.4 Hz, 1H), 8.05 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H),
7.79 (d, J = 8.0 Hz, 1H), 7.58 (td, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H), 7.49 (td, J1 = 7.6 Hz, J2 = 3.2 Hz, 2H),
13
7.37 (td, J1 = 7.6 Hz, J2 = 1.6 Hz, 1H) ppm; C NMR (100 MHz, CDCl3) δ 165.7, 152.8, 136.2, 134.5,
134.1, 132.2, 131.3, 127.6, 126.3, 125.5, 123.6, 122.1, 121.5 ppm.
2-(3-Bromophenyl)benzothiazole (3i) (CAS No.: 19654-14-9)
Following general procedure gave product 3i as a white solid. 77% yield; mp 120–121 ºC; 1H NMR (400
MHz, CDCl3) δ 8.32 (t, J = 1.6 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 8.04 (d, J = 7.6 Hz, 1H), 7.97 (d, J =
8.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 8.0 Hz,
13
1H) ppm; C NMR (100 MHz, CDCl3) δ 166.2, 154.0, 135.5, 135.1, 133.8, 130.5, 130.3, 126.6, 126.2,
125.6, 123.5, 123.2, 121.7 ppm.
2-(2-Methylphenyl)benzothiazole (3j) (CAS No.: 15903-58-9)
1
Following general procedure gave product 3j as a white solid. 94% yield; mp 56–57 ºC; H NMR (400
MHz, CDCl3) δ 8.18 (d, J = 8.4 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.83 (d, J = 7.6 Hz, 1H), 7.56 (t, J =
13
7.2 Hz, 1H), 7.48-7.35 (s, 4H), 2.72 (s, 3H) ppm; C NMR (100 MHz, CDCl3) δ 168.0, 153.8, 137.3,
135.6, 133.1, 131.6, 130.6, 130.0, 126.2, 126.1, 125.1, 123.4, 121.4, 21.4 ppm.
2-(3-Methylphenyl)benzothiazole (3k) (CAS No.: 1211-32-1)
1
Following general procedure gave product 3k as a white solid. 98% yield; mp 67–68 ºC; H NMR (400
MHz, CDCl3) δ 8.14 (d, J = 8.4 Hz, 1H), 8.00 (s, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 7.6 Hz, 1H),

HETEROCYCLES, Vol. 96, No. 7, 2018
1233
7.54 (td, J1 = 7.2 Hz, J2 = 1.6 Hz, 1H), 7.43 (td, J1 = 8.0 Hz, J2 = 0.8 Hz, 2H), 7.36 (d, J = 7.6 Hz, 1H),
2.53 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 168.4, 154.1, 138.9, 135.1, 133.5, 131.9, 129.0, 128.0,
126.3, 125.2, 124.9, 123.2, 121.6, 21.4 ppm.
2-(3,4-Dimethoxyphenyl)benzothiazole (3l) (CAS No.: 6638-45-5)
Following general procedure gave product 3l as a white solid. 50% yield; mp 130–131 ºC; 1H NMR (400
MHz, CDCl3) δ 8.09 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 2.4 Hz, 1H), 7.65 (dd, J1 =
8.4 Hz, J2 = 2.0 Hz, 1H), 7.53 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.42 (td, J1 = 7.2 Hz, J2 = 0.8 Hz, 1H),
13
6.99 (d, J = 8.4 Hz, 1H), 4.07 (s, 3H), 4.01 (s, 3H) ppm; C NMR (100 MHz, CDCl3) δ 168.0, 154.1,
151.6, 149.3, 134.9, 126.7, 126.3, 124.9, 122.9, 121.5, 121.2, 111.0, 109.8, 56.2, 56.1 ppm.
2-(4-Hydroxy-3-methoxyphenyl)benzothiazole (3m) (CAS No.: 36341-25-0)
1
Following general procedure gave product 3m as a white solid. 46% yield; mp 166–168 ºC; H NMR
(400 MHz, CDCl3) δ 8.08 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 2.0 Hz, 1H), 7.61 (dd,
J1 = 8.4 Hz, J2 = 2.0 Hz, 1H), 7.53 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.42 (td, J1 = 8.0 Hz, J2 = 0.8 Hz,
1H), 7.06 (d, J = 8.4 Hz, 1H), 6.00 (s, 1H), 4.08 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) δ 168.1, 154.1,
148.5, 146.9, 134.9, 126.3, 126.2, 124.8, 122.8, 122.0, 121.5, 114.7, 109.3, 56.3 ppm.
2-(6-Nitrobenzo[1,3]dioxol-5-yl)benzothiazole (3n)
1
Following general procedure gave product 3n as a yellow solid. 63% yield; mp 146–147 ºC; H NMR
(400 MHz, CDCl3) δ 8.12 (d, J = 7.2 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.57 (td, J1 = 7.2 Hz, J2 = 1.2 Hz,
1H), 7.54 (s, 1H), 7.48 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.16 (s, 1H), 6.25 (s, 2H) ppm; 13C NMR (100
MHz, CDCl3) δ 162.8, 153.3, 151.0, 149.3, 143.5, 136.0, 126.5, 125.8, 124.5, 123.8, 121.6, 110.7, 105.8,
103.6 ppm.
2-(Naphthalen-1-yl)benzothiazole (3o) (CAS No.: 56048-50-1)
Following general procedure gave product 3o as a white solid. 87% yield; mp 125–126 ºC; 1H NMR (400
MHz, CDCl3) δ 8.98 (d, J = 8.8 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.01-7.93 (m, 4H), 7.66-7.55 (m, 4H),
13
7.48 (td, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H) ppm; C NMR (100 MHz, CDCl3) δ 167.5, 154.1, 135.4, 134.0,
131.0, 130.8, 130.6, 129.3, 128.4, 127.6, 126.5, 126.2, 125.8, 125.2, 124.9, 123.5, 121.3 ppm.
2-(Furan-2-yl)-1,3-benzothiazole (3p) (CAS No.: 1569-98-8)
1
Following general procedure gave product 3p as a gray solid. 79% yield; mp 90–91 ºC; H NMR (400
MHz, CDCl3) δ 8.10 (d, J = 8.0 Hz, 1H), 7.94 (dd, J1 = 8.0 Hz, J2 = 0.4 Hz, 1H), 7.65 (dd, J1 = 1.6 Hz, J2
= 0.8 Hz, 1H), 7.53 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.42 (td, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.24 (dd, J1
= 3.2 Hz, J2 = 0.8 Hz, 1H), 6.64 (dd, J1 = 3.6 Hz, J2 = 2.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3) δ
157.6, 153.8, 148.8, 144.7, 134.3, 126.5, 125.2, 123.1, 121.6, 112.6, 111.5 ppm.
2-Cyclohexylbenzothiazole (3q) (CAS No.: 40115-03-5)
1
Following general procedure gave product 3q as a yellow oil. 78% yield; H NMR (400 MHz, CDCl3) δ

1234
HETEROCYCLES, Vol. 96, No. 7, 2018
8.02 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.88 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.48 (t, J = 8.4 Hz, 1H),
7.36 (t, J1 = 8.4 Hz, 1H), 3.17-3.11 (m, 1H), 2.27-2.21 (m, 2H), 1.95-1.89 (m, 2H), 1.73-1.63 (m, 2H),
13
1.54-1.30 (m, 4H) ppm; C NMR (100 MHz, CDCl3) δ 177.6, 153.1, 134.6, 125.8, 124.5, 122.6, 121.6,
43.5, 33.5, 26.1, 25.8 ppm.
2-Cyclopentylbenzothiazole (3r) (CAS No.: 40115-02-4)
1
Following general procedure gave product 3r as a yellow oil. 70% yield; H NMR (400 MHz, CDCl3) δ
8.01 (d, J = 8.0 Hz, 1H), 7.88 (dd, J1 = 8.0 Hz, J2 = 0.8 Hz, 1H), 7.48 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H),
7.37 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 3.62-3.57 (m, 1H), 2.30-2.00 (m, 2H), 1.99-1.87 (m, 4H),
13
1.80-1.77 (m, 2H) ppm; C NMR (100 MHz, CDCl3) δ 177.1, 153.2, 134.8, 125.8, 124.5, 122.5, 121.5,
44.8, 34.1, 25.6 ppm.
2-Cyclopropylbenzothiazole (3s) (CAS No.: 1248473-57-5)
1
Following general procedure gave product 3s as a yellow oil. 64% yield; H NMR (400 MHz, CDCl3) δ
7.94 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.46 (td, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 7.35 (td, J1 = 8.0
13
Hz, J2 = 1.2 Hz, 1H), 2.48-2.41 (m, 1H), 1.30-1.26 (m, 4H) ppm; C NMR (100 MHz, CDCl3) δ 174.5,
153.4, 134.1, 125.9, 124.3, 122.1, 121.4, 15.3, 11.7 ppm.
2-Isopropyl-1,3-benzothiazole (3t) (CAS No.: 17626-86-7)
1
Following general procedure gave product 3t as a yellow oil. 85% yield; H NMR (400 MHz, CDCl3) δ
8.03 (d, J = 8.4 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.48 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.37 (td, J1 = 8.4
13
Hz, J2 = 1.2 Hz, 1H), 3.52-3.41 (m, 1H), 1.51 (d, J = 6.8 Hz, 6H) ppm; C NMR (100 MHz, CDCl3) δ
178.6, 153.2, 134.7, 125.9, 124.6, 122.6, 121.6, 34.1, 23.0 ppm.
2-(1-Methylpropyl)-2-benzothiazole (3u) (CAS No.: 17626-87-8)
1
Following general procedure gave product 3u as a pale yellow oil. 83% yield; H NMR (400 MHz,
CDCl3) δ 8.03 (d, J = 8.0 Hz, 1H), 8.89 (d, J = 8.0 Hz, 1H), 7.48 (td, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 7.37
(td, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 3.30-3.21 (m, 1H), 2.01-1.90 (m, 1H), 1.87-1.78 (m, 1H), 1.50 (d, J =
13
6.8 Hz, 3H), 1.02 (t, J = 7.2 Hz, 3H) ppm; C NMR (100 MHz, CDCl3) δ 177.9, 153.1, 134.7, 125.8,
124.6, 122.6, 121.6, 41.1, 30.7, 20.8, 11.9 ppm.
1-Methyl-2-(1-phenylethyl)benzothiazole (3v) (CAS No.: 111259-61-1)
1
Following general procedure gave product 3v as a white solid. 68% yield; mp 34–36 ºC; H NMR (400
MHz, CDCl3) δ 8.07 (d, J = 8.0 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.52-7.33 (m, 7H), 4.65 (q, J = 7.6 Hz,
13
1H), 1.93 (d, J = 6.8 Hz, 3H) ppm; C NMR (100 MHz, CDCl3) δ 176.4, 153.2, 143.2, 135.4, 128.8,
127.7, 127.3, 125.9, 124.8, 122.9, 121.5, 44.9, 21.3 ppm.
6-Bromo-2-phenylbenzothiazole (3w) (CAS No.: 77333-67-6)
1
Following general procedure gave product 3w as a yellow solid. 85% yield; mp 149–150 ºC; H NMR
(400 MHz, CDCl3) δ 8.13-8.09 (m, 3H), 7.97 (d, J = 8.8 Hz, 1H), 7.65 (dd, J1 = 8.8 Hz, J2 = 2.0 Hz, 1H),

HETEROCYCLES, Vol. 96, No. 7, 2018
1235
13
7.55 (dd, J1 = 5.2 Hz, J2 = 2.0 Hz, 3H) ppm; C NMR (100 MHz, CDCl3) δ 168.6, 153.0, 136.7, 133.2,
131.3, 129.9, 129.1, 127.6, 124.3, 124.2, 118.8 ppm.
6-Methoxy-2-phenylbenzothiazole (3x) (CAS No.: 10205-69-3)
Following general procedure gave product 3x as a white solid. 69% yield; mp 112–113 ºC; 1H NMR (400
MHz, CDCl3) δ 8.10-8.08 (m, 2H), 8.01 (d, J = 8.8 Hz, 1H), 7.55-7.50 (m, 3H), 7.41 (d, J = 2.8 Hz, 1H),
13
7.15 (dd, J1 = 8.8 Hz, J2 = 2.8 Hz, 1H), 3.94 (s, 3H) ppm; C NMR (100 MHz, CDCl3) δ 165.6, 157.8,
148.7, 136.4, 133.8, 130.6, 129.0, 127.3, 123.7, 115.7, 104.2, 55.8 ppm.
1,3-Benzothiazol-2-yl(phenyl)methanone (5a) (CAS No.: 1629-75-0)
Following general procedure gave product 5a as a yellow solid. 90% yield; mp 99–100 ºC; 1H NMR (400
MHz, CDCl3) δ 8.61 (d, J = 7.2 Hz, 2H), 8.30 (dd, J1 = 8.4 Hz, J2 = 1.2 Hz, 1H), 8.07 (d, J = 6.8 Hz, 1H),
13
7.75-7.70 (m, 1H), 7.66-7.58 (m, 4H) ppm; C NMR (100 MHz, CDCl3) δ 185.4, 167.1, 153.9, 137.0,
135.0, 133.9, 131.3, 128.5, 127.7, 127.0, 125.8, 122.2 ppm.
(6-Methoxybenzothiazol-2-yl)(phenyl)methanone (5b) (CAS No.: 1443988-40-6)
1
Following general procedure gave product 5b as a yellow solid. 75% yield; mp 168–170 ºC; H NMR
(400 MHz, DMSO-d6) δ 8.46 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 9.2 Hz, 1H), 8.87 (s, 1H), 7.78-7.76 (m,
1H), 7.68-7.64 (m, 2H), 7.30 (dd, J1 = 8.8 Hz, J2 = 2.8 Hz, 1H), 3.92 (s, 3H) ppm; 13C NMR (100 MHz,
DMSO-d6) δ 185.2, 164.6, 160.1, 148.4, 139.0, 135.2, 134.4, 131.2, 129.1 126.7, 118.4, 104.9, 56.4 ppm.
(6-Nitrobenzo[d]thiazol-2-yl)(phenyl)methanone (5c) (CAS No.: 1443988-41-7)
1
Following general procedure gave product 5c as a yellow solid. 69% yield; mp 159–161 ºC; H NMR
(400 MHz, CDCl3) δ 9.01 (d, J = 2.0 Hz, 1H), 8.63 (d, J = 7.2 Hz, 2H), 8.51 (dd, J1 = 8.8 Hz, J2 = 2.4 Hz,
1H), 8.42 (d, J = 8.4 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.64 (t, J = 8.0 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3) δ 184.4, 172.4, 157.2, 146.5, 137.1, 134.6, 134.2, 131.4, 128.8, 126.2, 122.1, 118.9 ppm.
1-(1,3-Benzothiazol-2-yl)ethanone (5d) (CAS No.: 1629-78-3)
1
Following general procedure gave product 5d as a yellow solid. 81% yield; mp 107–109 ºC; H NMR
(400 MHz, CDCl3) δ 8.23 (d, J = 7.2 Hz, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.62 (td, J1 = 7.2 Hz, J2 = 1.6 Hz,
13
1H), 7.57 (td, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 2.87 (s, 3H) ppm; C NMR (100 MHz, CDCl3) δ 193.2,
166.5, 153.6, 137.5, 127.7, 127.0, 125.5, 122.5, 26.2 ppm.
ACKNOWLEDGEMENTS
This work has been supported by the National Natural Science Foundation of China (21202092),
Supported by Natural Science Foundation of Hubei Province of China (2018CFB241), China Three
Gorges University (KJ2014H008, KJ2014B084).

1236
HETEROCYCLES, Vol. 96, No. 7, 2018
REFERENCES
1. (a) P. C. Sharma, K. K. Bansal, A. Deep, and M. Pathak, Curr. Top. Med. Chem., 2017, 17, 208; (b)
R. S. Keri, M. R. Patil, S. A. Patil, and S. Budagumpi, Eur. J. Med. Chem., 2015, 89, 207; (c) S.
Agarwal, D. Gandhi, and P. Kalal, Lett. Org. Chem., 2017, 14, 729; (d) A. Rouf and C. Tanyeli, Eur.
J. Med. Chem., 2015, 97, 911.
2. (a) B. Gong, F. Hong, C. Kohm, L. Bonham, and P. Klein, Bioorg. Med. Chem. Lett., 2004, 14, 1455;
(b) E. L. Stone, F. Citossi, R. Singh, B. Kaur, M. Gaskell, P. B. Farmer, A. Monks, C. Hose, M. F. G.
Stevens, C.-O. Leong, M. Stocks, B. Kellam, M. Marlow, and T. D. Bradshaw, Bioorg. Med. Chem.,
2015, 23, 6891; (c) S. Aiello, G. Wells, E. L. Stone, H. Kadri, R. Bazzi, D. R. Bell, M. F. G. Stevens,
C. S. Matthews, T. D. Bradshaw, and A. D. Westwell, J. Med. Chem., 2008, 51, 5135; (d) T. D.
Bradshaw and A. D. Westwell, Cur. Med. Chem., 2004, 11, 1009; (e) C. W. Phoon, P. Y. Ng, A. E.
Ting, S. L. Yeo, and M. M. Sim, Bioorg. Med. Chem. Lett., 2001, 11, 1647.
3. (a) N. Parikh, D. Kumar, S. R. Roy, and A. K. Chakraborti, Chem. Commun., 2011, 47, 1797; (b) Y.
Riadi, R. Mamouni, R. Azzalou, M. E. Haddad, S. Routier, G. Guillaumet, and S. Lazar,
Tetrahedron Lett., 2011, 52, 3492; (c) K. Bahrami, M. M. Khodaei, and F. Naali, J. Org. Chem.,
2008, 73, 6835; (d) D. W. Hein, R. J. Alheim, and J. J. Leavitt, J. Am. Chem. Soc., 1957, 79, 427; (e)
H. Sharghi and O. Asemani, Synth. Commun., 2009, 39, 860; (f) S. Rudrawar, A. Kondaskar, and A.
K. Chakraborti, Synthesis, 2005, 15, 2521; (g) R. N. Nadaf, S. A. Siddiqui, T. Daniel, R. J. Lahoti,
and K. V. Srinivasan, J. Mol. Catal. A: Chem., 2004, 214, 155; (h) G. M. Raghavendra, A. B.
Ramesha, C. N. Revanna, K. N. Nandeesh, K. Mantelingu, and K. S. Rangappa, Tetrahedron Lett.,
2011, 52, 5571; (i) C. D. Wilfred and R. J. K. Taylor, Synlett, 2004, 1628; (j) M. Humenik, P.
Kutschy, K. Valkova, B. Horvath, V. Kovacik, and S. Bekesova, Chem. Commun., 2005, 70, 72.
4. (a) T. J. Williams and I. J. S. Fairlamb, Tetrahedron Lett., 2013, 54, 2906; (b) L. Ackermann, S.
Barfüsser, and J. Pospech, Org. Lett., 2010, 12, 724; (c) M. Zhang, S. Zhang, M. Liu, and J. Cheng,
Chem. Commun., 2011, 47, 11522; (d) K. E. Balsane, S. H. Gund, and J. M. Nagarkar, Catal.
Commun., 2017, 89, 29; (e) F. Zhu, J.-L. Tao, and Z.-X. Wang, Org. Lett., 2015, 17, 4926; (f) K. Xie,
Z. Yang, X. Zhou, X. Li, S. Wang, Z. Tan, X. An, and C.-C. Guo, Org. Lett., 2010, 12, 1564; (g) R.
S. Shelkar, K. E. Balsane, and J. M. Nagarkar, Tetrahedron Lett., 2015, 56, 693; (h) S. Ranjit and X.
Liu, Chem. Eur. J., 2011, 17, 1105; (i) F. Zhu and Z.-X. Wang, Org. Lett., 2015, 17, 1601; (j) W.
Zhang, Y. Tian, N. Zhao, Y. Wang, J. Li, and Z. Wang, Tetrahedron, 2014, 70, 6120; (k) D. Yu, L.
Lu, and Q. Shen, Org. Lett., 2013, 15, 940; (l) P. Yang, R. Wang, H. Wu, Z. Du, and Y. Fu, Asian J.
Org. Chem., 2017, 6, 184; (m) F. Yang, J. Koeller, and L. Ackermann, Angew. Chem. Int. Ed., 2016,
55, 4759; (n) G. Satish, K. H. V. Reddy, B. S. P. Anil, K. Ramesh, R. U. Kumar, and Y. V. D.
Nageswar, Tetrahedron Lett., 2015, 56, 4950; (o) D. Saha, L. Adak, and B. C. Ranu, Tetrahedron

HETEROCYCLES, Vol. 96, No. 7, 2018
1237
Lett., 2010, 51, 5624; (p) N. S. Nandurkar, M. J. Bhanushali, M. D. Bhor, and B. M. Bhanage,
Tetrahedron Lett., 2008, 49, 1045; (q) H. Liu, H. Xu, and Y. Yuan, Tetrahedron, 2014, 70, 6474; (r)
E. Kianmehr, M. Fardpour, and A. N. Kharat, Eur. J. Org. Chem., 2017, 2017, 3017; (s) W.-Y. Hu,
P.-P. Wang, and S.-L. Zhang, Synthesis, 2015, 47, 42; (t) M. G. Hanson, N. M. Olson, Z. Yi, G.
Wilson, and D. Kalyani, Org. Lett., 2017, 19, 4271; (u) Y. Han, X. Wang, X. Wang, L. Lv, G. Diao,
and Y. Yuan, Synthesis, 2012, 44, 3027; (v) S. Fan, Z. Chen, and X. Zhang, Org. Lett., 2012, 14,
4950; (w) S. Pivsa-Art, T. Satoh, Y. Kawamura, M. Miura, and M. Nomura, Bull. Chem. Soc. Jpn.,
1998, 71, 467; (x) A. Mori, A. Sekiguchi, K. Masui, T. Shimada, M. Horie, K. Osakada, M.
Kawamoto, and T. Ikeda, J. Am. Chem. Soc., 2003, 125, 1700.
5. (a) M. Zhang, W.-T. Lu, W. Ruan, H.-J. Zhang, and T.-B. Wen, Tetrahedron Lett., 2014, 55, 1806;
(b) S. Liu, R. Chen, X. Guo, H. Yang, G. Deng, and C.-J. Li, Green Chem., 2012, 14, 1577; (c) Z.
Yang, X. Chen, S. Wang, J. Liu, K. Xie, A. Wang, and Z. Tan, J. Org. Chem., 2012, 77, 7086; (d) Y.
Gao, Q. Song, G. Cheng, and X. Cui, Org. Biomol. Chem., 2014, 12, 1044; (e) Q. Song, Q. Feng,
and M. Zhou, Org. Lett., 2013, 15, 5990; (f) A. Kamal, N. V. S. Reddy, and B. Prasad, Tetrahedron
Lett., 2014, 55, 3972.
6. D. Pi, H. Zhou, P. Cui, R. He, and Y. Sui, ChemistrySelect, 2017, 2, 3976.
7. M. Liu and C.-J. Li, Angew. Chem. Int. Ed., 2016, 55, 10806.
8. (a) G. Dannhardt, B. L. Fiebich, and J. Schweppenhäuser, Eur. J. Med. Chem., 2002, 37, 147; (b) C.
W. Hummel, A. G. Geiser, H. U. Bryant, I. R. Cohen, R. D. Dally, K. C. Fong, S. A. Frank, R.
Hinklin, S. A. Jones, G. Lewis, D. J. McCann, D. G. Rudmann, T. A. Shepherd, H. Tian, O. B.
Wallace, M. Wang, Y. Wang, and J. A. Dodge, J. Med. Chem., 2005, 48, 6772.
9. (a) S. Liu, R. Chen, H. Chen, and G.-J. Deng, Tetrahedron Lett., 2013, 54, 3838; (b) J. Wang, X.-Z.
Zhang, S.-Y. Chen, and X.-Q. Yu, Tetrahedron, 2014, 70, 245.
10. Z. Yang, A. Wang, X. Chen, Q. Gui, J. Liu, Z. Tan, H. Wang, and J.-C. Shi, Synlett, 2013, 24, 1549.