Elemental sulfur mediated cyclization via redox strategy: Synthesis of benzothiazoles from o-chloronitrobenzenes and benzyl chlorides

Article abstract of DOI:10.1016/j.tet.2017.07.013

A novel metal-free synthesis of 2-substituted benzothiazoles from easily available o-chloronitrobenzenes and benzyl chlorides using elemental sulfur as traceless oxidizing agent has been developed. The protocol provides a simple, efficient, and atom-economic way to access to benzothiazoles in moderate to excellent yields. And the approach exhibited good functional group tolerance.

Full text of DOI:10.1016/j.tet.2017.07.013

Accepted Manuscript
Elemental sulfur mediated cyclization via redox strategy: Synthesis of benzothiazoles
from o-chloronitrobenzenes and benzyl chlorides
Xin Wang, Dazhuang Miao, Xiaotong Li, Renhe Hu, Zhao Yang, Ren Gu, Shiqing Han
PII:
S0040-4020(17)30737-8
10.1016/j.tet.2017.07.013
TET 28845
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 26 May 2017
Revised Date: 4 July 2017
Accepted Date: 8 July 2017
Please cite this article as: Wang X, Miao D, Li X, Hu R, Yang Z, Gu R, Han S, Elemental sulfur mediated
cyclization via redox strategy: Synthesis of benzothiazoles from o-chloronitrobenzenes and benzyl
chlorides, Tetrahedron (2017), doi: 10.1016/j.tet.2017.07.013.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Elemental Sulfur Mediated Cyclization via
Redox Strategy: Synthesis of Benzothiazoles
from o-Chloronitrobenzenes and Benzyl
Chlorides
Leave this area blank for abstract info.
Xin Wanga , Dazhuang Miaoa , Xiaotong Lia , Renhe Hua , Zhao Yanga, Ren Gua, and Shiqing Han a,b,
a College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, CAS,
345 Lingling Road, Shanghai 200032, China

ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Elemental Sulfur Mediated Cyclization via Redox Strategy: Synthesis of
Benzothiazoles from o-Chloronitrobenzenes and Benzyl Chlorides
Xin Wanga , Dazhuang Miaoa , Xiaotong Lia , Renhe Hua , Zhao Yanga, Ren Gua, and Shiqing Han a,b,
a College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, China
b Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, CAS, 345 Lingling Road, Shanghai 200032, China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel metal-free synthesis of 2-substituted benzothiazoles from easily available o-
chloronitrobenzenes and benzyl chlorides using elemental sulfur as traceless oxidizing agent has
been developed. The protocol provides a simple, efficient, and atom-economic way to access to
benzothiazoles in moderate to excellent yields. And the approach exhibited good functional
group tolerance.
Available online
Keywords:
benzothiazoles
benzyl chlorides
elemental sulfur
cyclization
2017 Elsevier Ltd. All rights reserved
.
redox strategy
1. Introduction
2-Substituted benzothiazole derivatives represent an important
class of heterocyclic compounds which play essential roles as
key blocks in the synthesis of a variety of drugs such as
antitumoral, antimicrobial, anti-inflammatory and anticonvulsant
agents.1,2 Thus, there are numerous efforts aimed at developing
efficient methods for rapid construction of benzothiazoles.
The conventional wisdom approaches for the synthesis of
these compounds typically rely on the condensation of 2-
aminothiophenols with aldehydes3 or carboxylic acids4 under
oxidative conditions, the oxidative cross-coupling of
benzothiazoles and phenylacetic acids5 or intramolecular
cyclization of 2-haloanilides catalyzed by transition metal6.
However, these reactions are suffering from difficulties in
preparation of starting materials, application of excess added
agents, and harsh reaction conditions. To overcome these
limitations, it is crucial to make a valid and practical protocol for
the construction of C-C and C-S bonds in a direct step- and atom-
economical approach.7 To the best of our knowledge, the strategy
for the redox reactions has become a powerful tool to synthesize
heterocyclic compounds, as it is highlighted by the direct product
formation without an added agent such as oxidant, reductant, acid
or base.8 Recently, our group disclosed a green and novel
Scheme 1. Access to 2-Substituted Benzothiazoles
external oxidant or reductant (Scheme 1a).9a And meanwhile,
Nguyue group also illuminated an analogical methodology.9b
A
decarboxylative redox reaction using o-chloronitroarenes,
arylacetic acids and elemental sulfur as substrates under solvent-
and catalyst-free conditions has been developed by Guntreddi
group (Scheme 1b).10 Thus it can be seen that elemental sulfur
which is readily available, nontoxic, and stable under ambient
conditions plays a vital role in redox reactions as oxidant and
reductant due to its valence states diversity, ranging from -2 to
+6.11 In addition, our lab has reported a metal-free approach to
benzothiazoles from benzyl chlorides and 2-mercaptan anilines
synthesis
of
2-substituted
benzothiazoles
from
2-
chloronitrobenzenes and aliphatic amines via elemental sulfur
mediated redox cyclization in the absence of
———
Corresponding author. Tel.: + 86 25 58139970; fax: + 86 25 58139369; e-mail: hanshiqing@njtech.edu.cn (S. Han).

2
Tetrahedron
ACCEPTED MANUSCRIPT
using elemental sulfur as traceless oxidizing angent (Scheme
3ak) underwent the redox process to afford the expected products
1c). Furthermore, benzyl chloride derivatives are a family of
inexpensive organic intermediates and served as new and
potential acyl sources.12,13
in good yields, whereas giving slightly inferior yields when the
substituents at ortho-position (3ad, 3al), probably as a result of
steric hindrance. However, we found that the electron-deficient
substituents did obviously affect the efficiency on the reaction
(3ao-3ar). The stronger were the substituents, the lower were the
yields. When benzyl chloride linked with nitro group on the
benzene ring, no product was obtained (3ar). Besides, α-naphthyl
and biphenyl group substrates were also compatible to give 3as-
3at in 65% and 47% yields, respectively. Notably,
heteroaromatic methyl chlorides also worked well under standard
conditions and offered 3au-3ax in moderate to good yields. On
the other hand, we also evaluated readily available substituted o-
chloronitrobenzenes tolerance in the present reaction conditions
subsequently. Much to our satisfaction, the presence of the
electron-donating groups such as methyl and methoxyl group
promoted the yields of the reaction (3ba-3da). Besides, the o-
chloronitrobenzenes bearing halo-substituted groups were all
well-tolerated under the standard reaction conditions and
transformed smoothly into expected products in 73%, 72%, 69%
and 73% yields, respectively (3ea-3ha).
Herein, we report an elemental sulfur mediated redox
condesation from benzyl chlorides and o-chloronitrobenzenes for
the synthesis of 2-substituted benzothiazoles under metal-free
conditions (Scheme 1d).
2. Results and discussion
As an exploratory study, benzyl chloride (1a) and o-
chloronitrobenzene (2a) were chosen as test substrates in the
presence of elemental sulfur (Table 1). As we expected, when
the reaction was carried out in N-methylpiperidine at 120 ℃ for
24 h under nitrogen atmosphere, the desired product 3aa was
obtained in 60% yield (entry 1). The amount of elemental sulfur
was an important factor for the yield of the product. And the use
of 1.5 equiv elemental sulfur led to a higher yield of 3aa (entries
2-3). To determine the effect of temperature on this approach,
these reactions were checked (entries 4-6),and the reaction yield
increased to 80% when the temperature was decreased to 110 ℃
(entry 5). We then investigated the impact of solvent on reaction
yield (entries 7-8), and it proved that N-methylpiperidine was
superior to others. Furthermore, reducing the reaction time to 18
h or prolonging to 36 h resulted in lower yields (entries 9-10).
To gain insights into the reaction mechanism, control experi-
Table 2. Reaction Scope and Versatilitya
Table 1. Optimization of the Reaction Conditionsa
entry
1
solvent
S (equiv)
yieldb (%)
temp (℃)
120
N-methylpiperidine
N-methylpiperidine
N-methylpiperidine
1
60
75
70
80
78
40
20
60
71
72
2
1.5
2
120
3
120
4
N-methylpiperidine 1.5
110
5
N-methylpiperidine
N-methylpiperidine
pyridine
1.5
1.5
1.5
1.5
1.5
1.5
100
6
90
7
110
8
9c
10d
Triethylamine
110
N-methylpiperidine
110
N-methylpiperidine
110
aReaction conditions: benzyl chloride (1 mmol), o-chloronitrobenzene
(0.5 mmol) in solvent (1.5 mL) under a nitrogen atmosphere for 24 h
at the specified reaction temperature.
bIsolated yield.
c18 h.
d36 h.
Now the optimal reaction conditions had been identified, the
scope of the multicomponent one-pot reaction was investigated
(Table 2). We first focused on the influence of various
benzyl chlorides on the reaction. The reaction with
benzyl chlorides bearing electron-donating groups could be
smoothly transformed into the desired products (3ab-3ah).
Furthermore, benzyl chlorides possessing 3, 4-dimethoxy or p-
tert-butyl also provided the corresponding products in good
yields (3ag-3ah). Additionally, this transformation also showed
satisfactory tolerance of halogen groups (3ai-3an), which provide
useful handles for further transformations through traditional
cross-coupling reactions. It is noteworthy that simple methyl or
bromine group at the para- and meta-positions (3ab, 3ac and
aReaction conditions: 1 (1 mmol), 2 (0.5 mmol), and elemental sulfur (1.5
mmol) in N-methylmorpholine (1.5 mL) under a nitrogen atmosphere at 110
℃ for 24 h. All reported yields are isolated yields.
ments were performed under standard conditions as highlighted
in Scheme 3. First, each couple of starting materials was heated
together at 110 ℃ for 24 h in N-methyilpiperidine (Scheme 2,

eqs 1-3): Treatment of benzyl choride 1a
N-
All solvents were obtained from commercial sources and used
without further purification. All experiments were conducted
ACCEwPiTthED MANUSCRIPT
methylpiperidine
was
transformed
into
1-benzyl-1-
methylpiperidine chloride; In contrast, reaction of sulfur with 2a
did not work and all starting materials were recovered unchanged.
Notably, when 1 equiv or 2 equiv radical trapping reagent
TEMPO was added to the reaction mixture, the expected product
3aa was obtained in 53% and 30% yields, respectively, which
was lower than that under standard conditions. Thus it indicated
that a radical pathway might be involved (Scheme 2, eq 4).
with a sealed pressure vessel. NMR spectra were recorded with a
300 MHz or 500 MHz spectrometer for H NMR on a Bruker
1
Avance 300 spectrometer with TMS as the internal standard and
CDCl3 as solvent, and 75 MHz for 13C NMR spectroscopy on a
Bruker Avance 300 spectrometer with TMS as the internal
standard using CDCl3 solution. Flash column chromatography
was performed over silica gel (200-300 mesh). All substrates are
known compounds and prepared according to the literature.
Cl
Cl
N-methylpiperidine
110℃ 24 h
N
(1)
+
Cl
+
2a
4.2. General experimental procedures
,
NO2
1a (1 mmol)
Cl
2a (0.5 mmol)
A mixture of o-chloronitrobenzene (0.5 mmol), benzyl
chloride (1.0 mmol), elemental sulfur (1.5 mmol) and N-
methylpiperidine (1.5 mL) was placed in a sealed pressure vessel
(25 mL) containing a magnetic stirring bar. The The tube was
purged with nitrogen three times, and then capped and stirred in a
preheated oil bath at 110 °C for 24 h. After the mixture was
cooled to room temperature, concentrated in vacuum and purified
by silica gel column chromatography by using petroleum ether
and ethyl acetate (PE:EA=1:500) as eluent.
N
N-methylpiperidine
110 24 h
(2)
S8
(1.5 equiv)
+
S8
Cl
+
℃,
1a (1 mmol)
Cl
N-methylpiperidine
recovery of 2a and S8
(3)
S8
+
110℃ 24 h
,
NO2
(1.5 equiv)
2a (1 mmol)
Cl
S
N
Cl
N-methylpiperidine
110 24 h
S8
+
+
(4)
℃,
NO2
(0.5 mmol)
(1.5 equiv)
1a (1 mmol)
3aa
2a
4.2.1. 2-Phenylbenzo[d]thiazole (3aa, CAS: 883-93-2)14. Llight
yellow solid (85 mg, 80%); H NMR (300 MHz, CDCl3) δ 8.09-
TEMPO (1 equiv)
TEMPO (2 equiv)
53%
30%
1
8.11 (m, 3H), 7.90 (d, J = 7.8 Hz, 1H), 7.48-7.52 (m, 4H), 7.38 (t,
J = 7.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 168.0, 154.1,
135.1, 133.6, 130.9, 129.0, 127.5, 126.2, 125.1, 123.2, 121.6.
4.2.2. 2-(m-Tolyl)benzo[d]thiazole (3ab, CAS: 1211-32-1)5a.
Light yellow solid (103 mg , 96%); 1H NMR (300 MHz, CDCl3):
δ 8.10 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.87-7.90 (m, 2H), 7.49
(t, J = 7.5 Hz, 1H), 7.38 (t, J = 7.5 Hz, 2H), 7.30 (d, J = 7.5 Hz,
1H), 2.46 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 168.2, 154.1,
138.8, 135.0, 133.5, 131.7, 128.8, 127.9, 126.2, 125.0, 124.8,
123.1, 121.5, 21.3.
4.2.3. 2-(p-Tolyl)benzo[d]thiazole (3ac, CAS: 16112-21-3)14.
Light yellow solid (94 mg, 87%); 1H NMR (300 MHz, CDCl3): δ
8.04 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 8.1 Hz, 2H), 7.85 (d, J = 8.1
Hz, 1H), 7.45 (t, J = 7.8 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.26 (d,
J = 7.5 Hz, 2H), 2.39 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
168.1, 154.2, 141.3, 134.9, 131.0, 129.6, 127.4, 126.1, 125.0,
123.0, 121.5, 21.4.
Scheme 2. Control experiments
On the basis of these above experiments and previous
literatures,9,10,12,13 a plausible mechanism is proposed in Scheme
3. At first, benzyl chloride 1a undergoes N-methylpiperidine to
produce 1-benzyl-methylpiperidinium chloride A. After that, in
the presence of elemental sulfur, A is oxidized to form
polysulfide B and the radical intermediate C is generated by the
sulfur extrusion, which reacts with the nitro group of 2a to yield
D subsequently. Then by the means of sulfuration of the
methylene, the intermediate D can be converted into E, which
eventually undergoes a cascade reaction of cyclization and
reduction to afford the desired product 3aa.
4.2.4. 2-(o-Tolyl)benzo[d]thiazole (3ad, CAS: 15903-58-9)6a.
Light yellow solid (55 mg, 51%); 1H NMR (300 MHz, CDCl3): δ
8.11 (d, J = 7.8 Hz, 1H), 7.94 (d, J = 7.5 Hz, 1H), 7.76 (d, J = 7.5
Hz, 1H), 7.51 (t, J = 8.4 Hz, 1H), 7.25-7.41 (m, 4H), 2.67 (s, 3H);
13C NMR (75 MHz, CDCl3): δ 167.9, 153.8, 137.2, 135.6, 133.1,
131.5, 130.5, 129.9, 126.1, 125.0, 124.8, 123.4, 121.3, 21.3.
Scheme 3. Plausible Mechanism
4.2.5. 2-(4-Methoxyphenyl)benzo[d]thiazole (3ae, CAS: 6265-
1
92-5)14. Light yellow solid (95 mg, 79%); H NMR (300 MHz,
3. Conclusion
CDCl3): δ 8.03 (d, J = 6.0 Hz, 3H), 7.86 (d, J = 7.5 Hz, 1H), 7.47
(t, J = 7.5 Hz, 1H), 7.34 (t, J = 6.9 Hz, 1H), 6.99 (d, J = 8.1 Hz,
2H), 3.85 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 167.8, 161.9,
154.2, 134.8, 129.0, 126.4, 126.1, 124.7, 122.8, 121.4, 114.3,
55.4.
In summary, we have developed a novel and facile approach
that elemental sulfur mediated direct construction of 2-
substituted benzothiazoles from readily available o-
chloronitrobenzenes and benzyl chlorides in the absence of
transition metal. This approach afforded 2-substituted
benzothiazoles in satisfactory yields with good substrate
tolerance. The reaction makes the process attractive and practical,
which is free from the use of metal or external oxidant. Further
investigations of the mechanism and applications are presently
underway.
4.2.6. 2-(3-Methoxyphenyl)benzo[d]thiazole (3af, CAS: 10002-
1
44-5)15. Light yellow solid (94 mg, 78%); H NMR (300MHz,
CDCl3): δ 8.09 (d, J = 8.1 Hz, 1H), 7.89 (d, J = 8.1 Hz, 1H),
7.64-7.69 (m, 2H), 7.49 (t, J = 8.1 Hz, 1H), 7.36-7.41 (m, 2H),
7.04 (dd, J = 2.4, 8.4 Hz, 1H), 3.91 (s, 3H); 13C NMR (75MHz,
CDCl3): δ 167.8, 160.0, 154.1, 135.1, 134.9, 130.0, 126.2, 125.2,
123.2, 121.5, 120.2, 117.3, 112.1, 55.4.
4. Experimental section
4.2.7. 2-(3,4-Dimethoxyphenyl)benzo[d]thiazole (3ag, CAS:
1
6638-45-5)12. Light yellow solid (94 mg, 69%); H NMR (300
4.1. General information

4
Tetrahedron
ACCEPTED MANUSCRIPT
MHz, CDCl3) δ 8.04 (d, J = 4.8 Hz, 1H), 7.87 (d, J = 4.8 Hz,
4.2.16. 2-(3-(Trifluoromethyl)phenyl)benzo[d]thiazole (3ap, CAS:
1H), 7.72 (s, 1H), 7.61 (d, J = 5.1 Hz, 1H), 7.47 (t, J = 4.8 Hz,
1H), 7.35 (t, J = 4.5 Hz, 1H), 6.95 (d, J = 5.1 Hz, 1H), 4.02 (s,
3H), 3.96 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.8, 154.1,
151.5, 149.3, 134.8, 126.6, 126.1, 124.8, 122.7, 121.4, 121.1,
111.0, 109.8, 56.0, 55.9.
133389-19-2)2e. Light yellow solid (120 mg, 86%); 1H NMR
(300 MHz, CDCl3) δ 8.39 (s, 1H), 8.26 (d, J = 7.7 Hz, 1H), 8.11
(d, J = 8.1 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.75 (d, J = 7.7 Hz,
1H), 7.63 (t, J = 7.8 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H), 7.43 (t, J =
7.5 Hz, 1H). 13C NMR (126 MHz, CDCl3) δ 166.1, 154.0, 135.1,
134.5, 131.8, 130.7, 129.6, 127.3 (d, J = 3.5 Hz), 126.6, 125.7,
124.9, 124.3 (d, J = 3.7 Hz), 123.6, 121.7; 19F NMR (282 MHz,
CDCl3) δ -61.67 (s).
4.2.8. 2-(4-tert-Butylphenyl)benzo[d]thiazole (3ah, CAS: 56048-
52-3)5a. Light yellow solid (102 mg, 76%); H NMR (300 MHz,
1
CDCl3): δ 8.08 (d, J = 8.1 Hz, 1H), 8.04 (d, J = 8.4 Hz, 2H), 7.89
(d, J = 7.8 Hz, 1H), 7.52 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 7.8 Hz,
1H), 7.35-7.40 (m, 1H), 1.38 (s, 9H); 13C NMR (75 MHz, CDCl3):
δ 168.1, 154.5, 154.2, 135.0, 130.9, 127.3, 126.2, 125.9, 125.0,
123.1, 121.5, 35.0, 31.2.
4.2.17. 2-(4-Cyanophenyl) benzo[d]thiazole (3aq, CAS: 17930-
02-8)1c. Light yellow solid (61 mg, 52%); H NMR (300 MHz,
1
CDCl3) δ 8.15 (d, J = 8.4 Hz, 2H), 8.09 (d, J = 8.2 Hz, 1H), 7.91
(d, J = 7.8 Hz, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.50-7.55 (m, 1H),
7.40-7.45 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 165.2, 154.0,
137.4, 135.2, 132.6, 127.8, 126.7, 126.0, 123.7, 121.7, 118.2,
114.0.
4.2.9. 2-(3-Chlorophenyl)benzo[d]thiazole (3ai, CAS: 22868-31-
1)5a. Light yellow solid (96 mg, 78%); 1H NMR (300 MHz,
CDCl3): δ 8.07-8.11 (m, 2H), 7.87-7.93 (m, 2H), 7.36-7.52 (m,
4H); 13C NMR (75 MHz, CDCl3): δ 166.2, 154.0, 135.2, 135.10,
135.06, 130.8, 130.2, 127.3, 126.5, 125.6, 125.5, 123.4, 121.6.
4.2.18. 2-(Naphthalen-1-yl)benzo[d]thiazole (3as, CAS: 56048-
50-1)5a. Light yellow solid (85 mg, 65%); H NMR (300 MHz,
1
CDCl3) δ 8.94 (d, J = 8.1 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.93-
8.01 (m, 4H), 7.54-7.65 (m, 4H), 7.46 (t, J = 7.5 Hz, 1H); 13C
NMR (75 MHz, CDCl3) δ 167.5, 154.1, 135.4, 133.9, 131.0,
130.7, 130.6, 129.3, 128.3, 127.5, 126.4, 126.2, 125.8, 125.2,
124.9, 123.5, 121.3.
4.2.10. 2-(4-Chlorophenyl)benzo[d]thiazole (3aj, CAS: 6265-91-
4)5a. Light yellow solid (88 mg, 72%); 1H NMR (500 MHz,
CDCl3): δ 8.07 (d, J = 8.2 Hz, 1H), 8.04 (d, J = 8.3 Hz, 2H), 7.91
(d, J = 8.0 Hz, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 8.4. Hz,
1H), 7.41 (t, J = 7.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 166.5,
154.1, 137.0, 135.0, 132.1, 129.2, 128.7, 126.4, 125.4, 123.3,
121.6.
4.2.19. 2-([1,1'-Biphenyl]-4-yl)benzo[d]thiazole (3at, CAS:
1
67362-98-5)1a. Light yellow solid (68 mg, 47%); H NMR (300
MHz, CDCl3) δ 8.11-8.18 (m, 3H), 7.91 (d, J = 4.5 Hz, 1H),
7.66-7.73 (m, 4H), 7.40-7.50 (m, 5H); 13C NMR (75 MHz,
CDCl3) δ 167.6, 154.2, 143.7, 140.0, 135.1, 132.5, 128.9, 128.0,
127.6, 127.1, 126.3, 125.1, 123.2, 121.6.
4.2.11. 2-(4-Bromophenyl)benzo[d]thiazole (3ak, CAS: 19654-
1
19-4)12. Light yellow solid (104 mg, 72%); H NMR (300 MHz,
CDCl3): δ 8.06 (d, J = 7.5 Hz, 1H), 7.86-7.94 (m, 3H), 7.60 (d, J
= 7.5 Hz, 2H), 7.47-7.51 (m, 1H), 7.38-7.41 (m, 1H); 13C NMR
(75 MHz, CDCl3): δ 166.6, 154.0, 135.0, 132.5, 132.1, 128.8,
126.4, 125.4, 123.3, 121.6.
4.2.20. 2-(Pyridin-2-yl)benzo[d]thiazole (3au, CAS: 716-80-3)1a.
1
Light yellow solid (90 mg, 85%); H NMR (300 MHz, CDCl3) δ
8.70 (d, J = 4.8 Hz, 1H), 8.38 (d, J = 7.8 Hz, 1H), 8.10 (d, J = 8.1
Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.85 (t, J = 7.7 Hz, 1H), 7.51 (t,
J = 7.2 Hz, 1H), 7.37-7.44 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ 169.3, 154.2, 151.4, 149.5, 136.9, 136.1, 126.2, 125.5, 125.1,
123.5, 121.9, 120.7.
4.2.12. 2-(2-Bromophenyl)benzo[d]thiazole (3al, CAS: 22901-
1
00-4)12. Light yellow solid (65 mg, 45%); H NMR (300 MHz,
CDCl3): δ 8.14 (d, J = 7.8 Hz, 1H), 8.00 (dd, J = 1.5, 7.8 Hz, 1H),
7.95 (d, J = 8.1 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.51-7.56 (m,
1H), 7.42-7.56 (m, 2H), 7.31-7.36 (m, 1H); 13C NMR (75 MHz,
CDCl3): δ 165.5, 152.7, 136.1, 134.5, 134.0, 132.1, 131.2, 127.5,
126.2, 125.4, 123.6, 122.1, 121.4.
4.2.21. 2-(Pyridin-4-yl)benzo[d]thiazole (3av, CAS: 2295-38-7)1a.
1
Light yellow solid (75 mg, 71%); H NMR (300 MHz, CDCl3) δ
8.78 (d, J = 3.3 Hz, 2H), 8.14 (d, J = 5.1 Hz, 1H), 7.94-7.97 (m,
3H), 7.55 (t, J = 4.8 Hz, 1H), 7.46 (t, J = 4.5 Hz, 1H); 13C NMR
(75 MHz, CDCl3) δ 165.0, 153.9, 150.7, 140.4, 135.2, 126.7,
126.1, 123.9, 121.8, 121.1.
4.2.13. 2-(4-Fluorophenyl)benzo[d]thiazole (3am, CAS: 1629-
1
26-1)14. Light yellow solid (80 mg, 70%); H NMR (300 MHz,
CDCl3): δ 8.05-8.10 (m, 3H), 7.88 (d, J = 8.1 Hz, 1H), 7.49 (t, J
= 7.8 Hz, 1H), 7.38 (t, J = 7.2 Hz, 1H), 7.17 (t, J = 8.4 Hz, 2H);
13C NMR (75 MHz, CDCl3): δ 166.6, 164.4 (d, J = 250.3 Hz),
154.0, 135.0, 130.0 (d, J = 3.2 Hz), 129.5 (d, J = 8.6 Hz), 126.4,
125.2, 123.2, 121.6, 116.1 (d, J = 22.0 Hz); 19F NMR (282 MHz,
CDCl3) δ -107.85 (s).
4.2.22. 2-(Thiophen-2-yl)benzo[d]thiazole (3aw, CAS: 34243-38-
4)1e. Light yellow solid (74 mg, 68%); 1H NMR (300 MHz,
CDCl3) δ 8.04 (d, J = 8.1 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.64
(d, J = 3.3 Hz, 1H), 7.44-7.50 (m, 2H), 7.36 (t, J = 7.5 Hz, 1H),
7.12 (t, J = 4.2 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 161.3,
153.7, 137.3, 134.7, 129.2, 128.5, 128.0, 126.3, 125.1, 122.9,
121.4.
4.2.14. 2-(3-Fluorophenyl)benzo[d]thiazole (3an, CAS: 1629-07-
1
8)12. Light yellow solid (109 mg, 95%); H NMR (300 MHz,
CDCl3): δ 8.09 (d, J = 8.1 Hz, 1H), 7.83-7.91 (m, 3H), 7.37-7.53
(m, 3H), 7.15-7.21 (m, 1H); 13C NMR (75 MHz, CDCl3): δ 164.7,
161.4, 154.0, 135.7 (d, J = 8.0 Hz), 135.1, 130.5 (d, J = 8.1 Hz),
126.5, 125.5, 123.4, 123.3 (d, J = 3.0 Hz), 121.6, 117.7 (d, J =
21.2 Hz), 114.3 (d, J = 23.3 Hz); 19F NMR (282 MHz, CDCl3) δ -
110.91 (s).
4.2.23. 2-(Furan-2-yl)benzo[d]thiazole (3ax, CAS: 1569-98-8 )1e.
1
Light yellow solid (72 mg, 71%); H NMR (300 MHz, CDCl3) δ
8.05 (d, J = 8.1 Hz, 1H), 7.89 (d, J = 7.8 Hz, 1H), 7.61 (s, 1H),
7.49 (t, J = 7.5 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.19 (d, J = 3.3
Hz, 1H), 6.60 (s, 1H). 13C NMR (75 MHz, CDCl3) δ 157.5, 153.7,
148.7, 144.6, 134.3, 126.4, 125.1, 123.1, 121.5, 112.4, 111.3.
4.2.15. Ethyl 4-(benzo[d]thiazol-2-yl)benzoate (3ao, CAS:
1
1030513-24-6)12. Light yellow solid (116 mg, 82%); H NMR
4.2.24. 6-Methyl-2-phenylbenzo[d]thiazole (3ba, CAS: 10205-
1
(300 MHz, CDCl3) δ 8.16 (s, 4H), 8.11 (d, J = 4.8 Hz, 1H), 7.93
(d, J = 4.8 Hz, 1H), 7.52 (t, J = 4.8 Hz, 1H), 7.42 (t, J = 4.5 Hz,
1H), 4.42 (q, J = 4.5 Hz, 2H), 1.43 (t, J = 4.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3) δ 166.5, 165.8, 154.1, 137.3, 135.2, 132.3,
130.1, 127.3, 126.5, 125.6, 123.5, 121.6, 61.2, 14.3.
58-0)12. Light yellow solid (81 mg, 72%); H NMR (300 MHz,
CDCl3) δ 8.07-8.10 (m, 2H), 7.97 (d, J = 8.4 Hz, 1H), 7.67 (s,
1H), 7.47-7.49 (m, 3H), 7.30 (dd, J = 1.2, 8.1 Hz, 1H), 2.49 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 166.9, 152.3, 135.3, 133.7,
130.7, 128.9, 127.8, 127.4, 126.2, 122.7, 121.3, 21.5.

4.2.25. 5-Methyl-2-phenylbenzo[d]thiazole (3ca, CAS: 107611-
References and notes
ACCEPTED MANUSCRIPT
1
15-4)5a. Light yellow solid (86 mg, 76%); H NMR (500 MHz,
CDCl3) δ 8.09-8.10 (m, 2H), 7.90 (s, 1H), 7.78 (d, J = 8.0 Hz,
1H), 7.49 (d, J = 3.5 Hz, 3H), 7.22 (d, J = 8.1 Hz, 1H), 2.52 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 168.0, 154.5, 136.3, 133.7,
132.0, 130.7, 128.9, 127.4, 126.7, 123.2, 121.0, 21.4.
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4.2.26. 5-Methoxy-2-phenylbenzo[d]thiazole (3da, CAS: 157328-
1
07-9)5a. Light yellow solid (100 mg, 83%); H NMR (500 MHz,
CDCl3) δ 8.08 (d, J = 3.5 Hz, 2H), 7.75 (d, J = 9.0 Hz, 1H), 7.58
(s, 1H), 7.49 (s, 3H), 7.05 (d, J = 9.0 Hz, 1H), 3.91 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 169.3, 159.2, 155.4, 133.7, 130.9,
129.0, 127.4, 121.8, 115.5, 105.6, 55.6.
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4.2.27. 7-Chloro-2-phenylbenzo[d]thiazole (3ea, CAS: 1242289-
1
39-9)9a. Light yellow solid (90 mg, 73%); H NMR (300 MHz,
CDCl3) δ 8.09 (d, J = 3.6 Hz, 2H), 7.95 (d, J = 7.5 Hz, 1H), 7.34-
7.51 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 168.7, 154.7, 135.3,
133.1, 131.3, 129.0, 127.5, 127.2, 126.8, 124. 8, 121.5.
4.2.28. 5-Chloro-2-phenylbenzo[d]thiazole (3fa, CAS: 952-16-
9)15. Light yellow solid (88 mg, 72%); 1H NMR (500 MHz,
CDCl3) δ 8.07-8.09 (m, 3H), 7.81 (d, J = 8.5 Hz, 1H), 7.52 (s,
3H), 7.37 (d, J = 8.5 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ
169.9, 155.0, 133.3, 133.2, 132.3, 131.3, 129.0, 127.6, 125.6,
123.0, 122.2.
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P. R.K.; Dulla, B.; Rao, M. V. B.; Manojit, P. Synth. Commun. 2013, 45,
3083-3092.
4.2.29. 5-Fluoro-2-phenylbenzo[d]thiazole (3ga, CAS: 1629-93-
2)12. Light yellow solid (79 mg, 69%); 1H NMR (300 MHz,
CDCl3) δ 8.05-8.08 (m, 2H), 7.73-7.81 (m, 2H), 7.4-7.05 (m, 3H),
7.11-7.18 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 170.5, 163.5,
160.3, 155.04 (d, J = 12.0 Hz), 133.4, 131.2, 130.4, 129.0, 127.5,
122.2 (d, J = 9.8 Hz), 113.8 (d, J = 25.7 Hz), 109.3 (d, J = 23.5
Hz); 19F NMR (282 MHz, CDCl3) δ -114.75 (s).
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4.2.30. 5-Bromo-2-phenylbenzo[d]thiazole (3ha, CAS: 305372-
1
56-9)9a. Light yellow solid (75 mg, 73%); H NMR (500 MHz,
CDCl3) δ 8.23 (s, 1H), 8.07-8.12 (m, 2H), 7.76 (d, J = 8.5 Hz,
1H), 7.49-7.51 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 169.6,
155.3, 133.8, 133.2, 131.3, 129.0, 128.2, 127.6, 126.0, 122.5,
119.8.
Acknowledgments
We thank to National High Technology Research and Develo-
pment Program of China (863 Program 2014AA022100), Six Ta-
lent Peaks Project in Jiangsu Province (No. 2015-SWYY-016) a-
nd Graduate Student Innovation Project in Jiangsu Province (Gr-
ant No. SJLX16_0304) for supporting this research).
Supplementary Material
(12) Gan, H.; Miao, D.; Pan, Q.; Hu, R.; Li, X.; Han, S. Chem. -Asian. J.
2016, 11, 1770-1774.
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Chem. 2016, 5, 1353-1358; (b) Nguyen, T. B.; Tran, M. Q.; Ermolenko, L.;
Al-mourabit, A. Org. Lett. 2014, 16, 310-313.
Supplementary data associated with this article can be found
in the online version.
General information, general experimental procedures,
1
characterization data of the products, and copies of the H, 13C
(14) Sun, Y.; Jiang, H.; Wu, W.; Zeng, W.; Wu, X. Org. Lett. 2013, 15,
1598-1601.
and 19F NMR spectra (PDF)
(15) Shi, X.; Guo, J.; Liu, J.; Ye, M.; Xu, Q. Chem. -Eur. J. 2015, 21, 9988.