N-Iodosuccinimide involved one-pot metal-free synthesis of 2-heteroaromatic benzothiazole compounds

Article abstract of DOI:10.1039/c6ob02731h

A one-pot protocol for the synthesis of structurally diverse 2-hetarylbenzothiazoles via oxidative condensation of the sp³ C-H bond with benzothiazoles has been described. This process is metal free and operationally simple. A series of 2-hetarylbenzothiazoles were prepared in moderate to good yield under mild conditions.

Full text of DOI:10.1039/c6ob02731h

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N-iodosuccinimide involved One-Pot Metal-free Synthesis of 2-
Heteroaromatic Benzothiazole Compounds
Xianglong Chua , Tiantian Duana, Xuan Liua, Lei Fenga, Jiong Jiaa, and Chen Ma*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
A one-pot protocol for the synthesis of structurally diverse 2-hetarylbenzothiazoles via oxidative condensation of sp3 C-H
bond with benzothiazoles has been described. This process is metal free and operationally simple. A series of 2-
hetarylbenzothiazoles were prepared in moderate to good yield under mild conditions.
DOI: 10.1039/x0xx00000x
www.rsc.org/
with benzothiazoles under mild conditions (Scheme 1, c).
Introduction
2-Substitued benzothiazole derivatives have been reported to
present promising activities, such as anti-carcinogenic,
antitumor, hydrolyse inhibitors, protease inhibitors1 and
fluorescent dyes.2
Results and discussion
Scheme 1. Synthesis of 2-hetarylbenzothiazoles
Traditionally, 2-subsititued benzothiazoles were obtained
by condensation of 2-aminothiophenol with aldehydes,
carboxylic acids, esters3 or transition-metal catalysed
benzothiazole cross-coupling with aryl halides.4 2-Haloanilines
as substrate forming 2-substitued benzothiazole was also
developed.5 In 2013, Song et al. reported a Cu-catalyzed
oxidative decarboxylative preparation of 2-aryl benzothiazole.6
Very recently, Wu and co-works described a protocol for the
cross-dehydrogenation coupling of quinoline N-oxide with
benzothiazole
affording
corresponding
2-subsititued
benzothiazole in good yield.7 However, these transformations
suffered from metal contamination, harsh reaction conditions
or difficulties in preparation of starting materials. In 2013,
Tynebor and co-works reported the synthesis of 2-(1,3-
benzothiazol-2-yl)quinolone from aryl tribromomethyl
functional group and 2-amino thiophenols.8 They provided a
novel method of synthesis 2-hetarylbenzothiazoles but with a
At the outset of our study, we chose 2-methylquinoline
(
1a) and benzothiazole (2a) as the model substrates to screen
the reaction conditions (Table 1). The reaction was performed
at 80 in DMSO under N2 atmosphere for 8 hours. Trace
unsatisfied yields. In 2014, we developed
a metal-free
℃
oxidative amination of sp3 C-H bond to synthesis 2-hetaryl-
quinazolin-4(3H)-ones (Scheme 1, a).9 In 2014, Gao and co-
amount of target compound was obtained in the absence of
iodine source, acid or oxidant (Table 1, entries 1-3). When TBAI,
KI were involved in the system, the starting materials afforded
trace amounts of the desired product (Table 1, entries 4-5). To
our delight, the corresponding product (3a) was obtained in a
yield of 36% and slightly improved in the presence of NIS
(Table 1, entries 6-7). We then investigated several acids. As a
result, CH3COOH proved to be the best acid giving the target
molecule in 65% yield (Table 1, entries 8-11). The oxidant was
also crucial for this reaction, DPTP and TPBP could promote
the transformation with a relatively lower yield (Table 1,
entries 12-13). Only trace amounts of desired product was
obtained when K2S2O8 was used as oxidant (Table 1, entry 14).
Finally, if the solvent was changed into toluene, DMF, or PhCl,
it caused lower yield of the product (Table 1, entries 15-17).
workers developed
arylaldehydes with
a
KI-catalyzed condensation of
benzothiazole receiving 2-aryl
benzothiazoles (Scheme 1, b).10 Inspired by these reports, we
envision a process for the synthesis of 2-hetarylbenzothiazoles
by the oxidative condensation of 2-methylquinoline derivatives
a.school of Chemistry and Chemical Engineering, Shandong University, Jinan,
250100, P R China.
b.State Key Laboratory of Bioactive Substance and Function of Natural Medicines,
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking
Union Medical College, Beijing, 100050, P. R. China. E-mail: chenma@sdu.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See DOI:
10.1039/x0xx00000x
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Product 3a could be obtained in 37% yield with longer reaction observed when 4-chloro-2-methylquinoline was employed as
time (32h) when a catalytic amount of NIS was used (Table 1, reaction substrate. Regretfully, 2-methylpyridine could not
entries 18). After completely screened the reaction convert to the corresponding product (Scheme 2, 3l). Then,
parameters, the optimized conditions was established as 2- we tried to use 3- and 4-methylpyridine and 3-methylquinoline
methylquinoline (1a) (0.5 mmol), benzothiazole (2a) (0.6 as substrates, the reactants were recovered and no desired
mmol), TBHP (2.0 mmol),
product generated. We also tried to use more convenient and
practicable 2-amino thiophenols as substrates oxidative
condensation with 4-methylquinoline, 2,6-dimethylquinoline
and 1-methylisoquinoline, but the corresponding product was
obtained in lower yield 52%, 30% and 45% respectively. Next,
various benzothiazoles were coupled with 2-methylquinoline
to give the corresponding molecule smoothly. Substrates with
an electron-donating substituent afforded higher yield than
Table 1. Optimization of the reaction conditions for the oxidative
condensation of 2-methylquinoline (1a) with benzothiazole (2a)
N
S
N
S
N
[I], acid, [O]
solvent
+
N
2a
1a
3a
that with an electron-withdrawing substituent (Scheme 2
3p). When substituent placed at the C4 position, the yield was
relatively lower than that at C6 position (Scheme 2 3q). Strong
, 3m-
entry
1
[I]
acid
[O]
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
toluene
DMF
yield, %b
trace
none
trace
trace
trace
36
TBAI
—
—
TBHP
TBHP
—
,
2
Ph2PO2H
Ph2PO2H
Ph2PO2H
Ph2PO2H
Ph2PO2H
Ph2PO2H
CH3CO2H
CF3CO2H
TsOH·H2O
PivOH
electron-withdrawing substituent such as –NO2 could not give
corresponding product (Scheme 2, 3r), We speculate that
Strong electron-withdrawing substituent has significant effect
on the oxidative condensation process. 6-Methoxy and 6-
chloro benzothiazole were discovered to work efficiently with
electron-donating and electron-withdrawing substitued
3
TBAI
TBAI
KI
4
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
TBPB
K2S2O8
TBHP
TBHP
TBHP
TBHP
5
6
I2
7
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
TBAI
NIS
57
quinolines (Scheme 2
, 3t-3y).
8
65
9
62
Scheme 2. Oxidative condensation of benothiazoles with
10
11
12
13
14
15
16
17
18c
63
quinoline derivatives.
60
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
CH3CO2H
50
45
trace
22
46
PhCl
23
DMSO
37
aReaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), acid (0.5
mmol), [I] (0.5 mmol), [O] (2 mmol) and solvent (1.5 mL), 80 oC,
under N2, 8 h. bIsolated yield. c[I] (0.05 mmol), 32 h.
NIS (0.5 mmol) and CH3COOH (0.5 mmol) at 80
℃ in DMSO
(1.5 mL) under a N2 atmosphere. The target molecule 3a was
obtained in 65% yield (Table 1, entry 8).
With the optimized reaction conditions in hand, the
substrate scope of this method was investigated. Various 2-
heteroaromatic benzothiazole Compounds were obtained in
fair to good yield (Scheme 2). For the substituted 2-
methylquinoline, both electron-donating groups and electron-
withdrawing groups could smoothly gave target molecules.
Generally, electron-donating groups on the quinoline ring gave
higher yields than those with electron-withdrawing groups
(Scheme
2
,
3a-3f). When 2-methylquinoxaline, 1-
methylisoquinoline, 4-methylquinoline was used as starting
material, the corresponding product was also obtained in
moderate yields (Scheme 2
derived from 3-methylbenzo[f]quinoline was also compatibly
gave the product in 39% yield (Scheme 2, 3j). However
, 3g-3i). In addition, quinoline
Control experiments were achieved to gain more insight
into the reaction mechanism (Scheme 3). Under the optimized
reaction conditions, 2-aminobenzenethiol was treated with 2-
，
under the optimized conditions, only 16% yield of 3k was
2 | J. Name., 2012, 00, 1-3
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methylquinoline affording 3a in 60% yield (Scheme 3, a). 2-
Methylquinoline could afford quinoline-2-carbaldehyde in 85%
yield under the standard conditions (Scheme 3, b). When
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) was added into
the reaction system, no desired product was observed. This
Substitued benzothiazoles were obtained according to the
literature reports.11 6-Ethoxybenzo[d]thiazole and 4-
methylbenzo[d]thiazole were also obtained using the same
way according to the reference 11. Other reagents and
solvents were commercially available and used directly
without further purification. All reactions were monitored by
TLC. 1H NMR spectra were recorded on a Bruker Avance 400 or
300 spectrometer at 400 or 300 MHz, using CDCl3 as solvent
and tetramethylsilane (TMS) as internal standard. 13C NMR
spectra were run in the same instrument at 100 or 75 MHz.
HRMS spectra were measured on a Q-TOF instrument in
positive-ion mode with an ESI ion source.
indicated the reaction might undergo
(Scheme 3, c).
a radical process
Scheme 4. Proposed reaction mechanism
tBuOOH
tBuO
+
HO-
SH
S
N
A
H
I+
1/2 I2
NH2
tBuOO + H2O
tBuOOH + OH-
2a'
2a
B
Scheme 3. Control experiments.
H+
tBuOO or
RO
-ROH
tBuO
OR
OR
N
N
H
N
N
H
(R = tBu or tBuO)
5
1a
1a'
Based on the above results and literature reports, we
proposed a plausible pathway for the reaction (Scheme 4). In
initially, TBHP was decomposed by iodide to obtain tert-
4
H+
H+
hydrolysis
RO
RO
OR
OR
OR
OR
OR
N
N
N
H
-ROH
S
H
butoxyl
A and tert-butylperoxy radical B. 2-Methylquinoline
8
7
6
isomerized into 1a’. methylpyridine and 3-methylquinoline
may be difficult to perform the dearomatization process. So,
no desired product generated.. Then, addition of a RO radical
HS
S
N
N
N
N
H
oxidation
N
N
H
N
CHO
with 1a’ formed the radical
give intermediate . After that, intermediate
and oxidized to form acetal 8. Hydrolysis of acetal led to the
formation of quinoline-2-carbaldehyde . With the assistant of
4
. Radical
4
was further oxidized to
3a
9
10
11
5
5
was isomerized
Typical Procedure for the Synthesis of 3
9
A mixture of 2-methylquinoline (1a) (0.5 mmol, 0.072 g),
benzothiazole (2a) (0.6 mmol, 0.081 g), TBHP (2.0 mmol, 0.257
g), NIS (0.5 mmol, 0.112 g) and CH3COOH (0.5 mmol, 0.003 g)
in DMSO (1.5 mL) was stirred at 80 oC under a nitrogen
atmosphere until the reaction was completeed (monitored by
TLC). The cooled reaction mixture was diluted with brine and
saturated Na2S2O3 (20 mL) and extracted with ethyl acetate (20
acid, the benzothiazole ring was opened, forming 2-
aminothiophenol 2a’.6 Finally, oxidative condensation 2a’ with
9
afforded 3a.
Conclusions
In conclusion, we have developed a method for the
mL
×3). The combined organic layers were dried with Na2SO4
synthesis of 2-hetarylbenzothiazoles by the oxidative
condensation of 2-methylquinoline derivatives with
benzothiazoles involved with NIS-TBHP. This method furnished
a one-pot, metal-free and simple strategy for the preparation
of 2-hetarylbenzothiazoles.
and evaporated under vacuum to afford the residue. The
residue was purified by column chromatography (silica gel)
with petroleum ether/ethyl acetate (10: 1) to obtain pure
product 3a.
2-(Quinolin-2-yl)benzo[d]thiazole 3a12. Light yellow solid (65%),
M.P.: 178-180 oC; H NMR (300 MHz, CDCl3): δ 8.51 (d, J = 8.4 Hz,
1
Acknowledgements
1H), 8.31 (d, J = 8.7 Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 7.8
Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.80 (td, J =
8.1, 1,2 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.57-7.50 (m, 1H), 7.47 (td, J
= 8.4, 1.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 169.85, 154.36,
151.31, 147.91, 137.01, 136.50, 130.11, 129.75, 129.00, 127.74,
127.59, 126.28, 125.88, 123.79, 122.03, 118.36; HRMS (ESI)
calculated for C16H10N2S (M+H)+ 263.0637; found: 263.0637.
We are grateful to the National Science Foundation of
China (No. 21572117) and State Key Laboratory of Bioactive
Substance and Function of Natural Medicines, Institute of
Materia Medica, Chinese Academy of Medical Sciences and
Peking Union Medical College (No. GTZK201405) for their
financial support.
2-(6-Methylquinolin-2-yl)benzo[d]thiazole 3b12. White solid (70%),
1
M.P.: 184-186 oC; H NMR (300 MHz, CDCl3): δ 8.44 (d, J = 9.0 Hz,
1H), 8.18 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 8.1 Hz, 1H), 8.09 (d, J = 8.4
Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.59-7.56 (m, 2H), 7.53 (td, J = 7.2,
Experimental
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1,2 Hz, 1H) 7.45 (td, J = 8.1, 1.2 Hz, 1H), 2.54 (s, 3H); 13C NMR (75 177 oC; 1H NMR (300 MHz, CDCl3): δ 9.04-8.99 (m, 2H), 8.24-8.20
MHz, CDCl3): δ 170.03, 154.37, 150.47, 146.49, 137.75, 136.42, (m, 2H), 8.00 (d, J = 7.8 Hz, 1H), 7.83-7.76 (m, 2H), 7.71-7.66 (m,
136.25, 132.41, 129.39, 129.05, 126.60, 126.21, 125.74, 123.69, 1H), 7.61(t, J = 7.5 Hz, 1H), 7.52 (t, J = 7.5 Hz, 1H); 13C NMR (100
121.99, 118.35, 21.73; HRMS (ESI) calculated for C17H12N2S (M+H)+ MHz, CDCl3): δ 164.75, 154.17, 149.73, 149.17, 138.29, 135.35,
277.0794; found: 277.0769.
129.97, 129.95, 128.13, 126.71, 126.13, 126.08, 124.97, 124.09,
2-(8-(Benzyloxy)quinolin-2-yl)benzo[d]thiazole 3c. White solid 122.14, 121.59; HRMS (ESI) calculated for C16H10N2S (M+H)+
o
(61%), M.P.: 236-238 C; 1H NMR (400 MHz, CDCl3): δ 8.52 (d, J = 263.0637; found: 263.0624.
8.5 Hz, 1H), 8.27 (d, J = 8.6 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 8.00 (d, J 2-(benzo[f]quinolin-3-yl)benzo[d]thiazole 3j. White solid (39%),
1
= 7.9 Hz, 1H), 7.69 (d, J = 7.4 Hz, 2H), 7.53-7.41 (m, 6H), 7.38 (d, J = M.P.: 232-234 oC; H NMR (300 MHz, CDCl3): δ 9.10 (d, J = 8.4 Hz,
7.3 Hz, 1H), 7.19 (dd, J = 6.4, 2.5 Hz, 1H); 5.46 (s, 2H); 13C NMR (100 1H), 8.69-8.62 (m, 2H), 8.16-7.95 (m, 5H), 7.76-7.60 (m, 2H), 7.56
MHz, CDCl3): δ 170.40, 154.79, 154.38, 150.09, 140.50, 137.26, (td, J = 7.2, 1.2 Hz, 1H), 7.47-7.42 (m, 1H);13C NMR (75 MHz, CDCl3):
136.97, 136.62, 130.35, 128.57,, 127.96, 127.78, 127.13, 126.22, δ 169.75, 154.45, 150.76, 148.03, 136.48, 132.12, 131,66, 131.57,
125.79, 123.71, 122.05, 120.29, 118.66, 112.01, 71.46; HRMS (ESI) 129.47, 128.83, 128.09, 127.83, 127.38, 126.54, 126.28, 125.77,
calculated for C23H16N2OS (M+H)+ 369.1056; found: 369.1057.
123.71, 123.04, 122.03, 118.46; HRMS (ESI) calculated for C20H12N2S
2-(7-Fluoroquinolin-2-yl)benzo[d]thiazole 3d. White solid (68%), (M+H)+ 313.0794; found: 313.0792.
o
M.P.: 202-204 C; 1H NMR (300 MHz, CDCl3): δ 8.48 (d, J = 8.7 Hz, 2-(4-Chloroquinolin-2-yl)benzo[d]thiazole 3K. White solid (16%),
1H), 8.30 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 7.8 M.P.: 190-192 oC; 1H NMR (300 MHz, CDCl3): δ 8.60 (s, 1H), 8.27 (dd,
Hz, 1H), 7.88-7.80 (m, 2H), 7.56 (td, J = 7.2, 1,2 Hz, 1H), 7.48 (td, J = J = 8.4, 0.6 Hz, 1H), 8.22 (d, J = 8.2 Hz, 1H), 8.15-8.12 (m, 1H), 7.99
7.8, 1.2 Hz, 1H), 7.41 (td, J = 8.4, 2.4 Hz, 1H); 13C NMR (75 MHz, (dd, J = 7.5, 0.3 Hz, 1H), 7.84-7.78 (m, 1H), 7.71-7.65 (m, 1H), 7.56
CDCl3): δ 169.38, 165.08 (d, J = 247.5 Hz), 154.22, 152.16, 148.93 (d, (td, J = 7.2, 1.2 Hz, 1H), 7.48 (td, J = 7.2, 1.2 Hz, 1H); 13C NMR (75
J = 12.8 Hz), 136.95, 136.47, 129.79 (d, J = 9.8 Hz), 126.38, 126.04, MHz, CDCl3): δ 167.48, 153.12, 150.12, 147.56, 142.55, 135.48,
125.97, 125.96, 123.83, 122.06, 118.26(d, J = 25.5 Hz), 117.74 (d, J = 129.91, 129.04, 127.47, 125.99, 125.43, 125.11, 123.24, 122.87,
2.4 Hz), 113.41 (d, J = 21.0 Hz); HRMS (ESI) calculated for C16H9N2SF 121.02, 117.46; HRMS (ESI) calculated for
(M+H)+ 281.0543; found: 281.0534.
297.0248; found: 297.0241.
2-(7-Chloroquinolin-2-yl)benzo[d]thiazole 3e. White solid (58%), 6-Fluoro-2-(quinolin-2-yl)benzo[d]thiazole 3m. Yellow solid (65%),
C
16H9ClN2S (M+H)+
1
o
M.P.: 214-216 oC; H NMR (300 MHz, CDCl3): δ 8.52 (d, J = 8.7 Hz, M.P.: 207-209 C; 1H NMR (300 MHz, CDCl3): δ 8.49 (d, J = 8.4 Hz,
1H), 8.30 (d, J = 8.7 Hz, 1H), 8.22 (d, J = 1.8 Hz, 1H), 8.16 (d, J = 8.1 1H), 8.33 (d, J= 8.7 Hz, 1H), 8.24 (d, J = 8.4Hz, 1H), 8.11-8.06 (m, 1H),
Hz, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.83 (d, J = 8.7 Hz, 1H), 7.57-7.51 (m, 7.90 (d, J = 8.1 Hz, 1H), 7.81-7.76 (m, 1H), 7.68-7.59 (m, 2H), 7.30-
2H), 7.49 (td, J= 8.1, 1,20 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 7.23 (m,1H); 13C NMR (75 MHz, CDCl3): δ 162.69 (d, J = 245.3 Hz);
169.31, 154.25, 152.21, 148.24, 136.88, 136.52, 136.09, 128.91, 150.94, 147.79, 137.76 (d, J = 11.3 Hz), 137.17, 130.23, 129.63,
128.66, 128.59, 127.31, 126.41, 126.10, 123.87, 122.09, 118.58; 128.99, 127.73, 127.70, 124.86 (d, J = 9.0 Hz), 118.21, 115.25 (d, J =
HRMS (ESI) calculated for C16H9N2SCl (M+H)+ 297.0248; found: 24.8 Hz), 108.30 (d, J = 26.3 Hz); HRMS (ESI) calculated for
297.0229.
2-(6-Bromoquinolin-2-yl)benzo[d]thiazole 3f. White solid (60%), 6-Methoxy-2-(quinolin-2-yl)benzo[d]thiazole 3n14
C16H9FN2S (M+H)+ 281.0543; found: 281.0563.
.
Yellow solid
M.P.: 240-242 oC; 1H NMR (400 MHz, CDCl3): δ 8.54 (d, J = 8.6 Hz (72%), M.P.: 178-180 oC; 1H NMR (300 MHz, CDCl3): δ 8.46 (d, J =
1H), 8.22 (d, J = 8.6 Hz, 1H), 8.16 (d, J = 8.1 Hz, 1H), 8.08-8.03 (m, 8.7 Hz, 1H), 8.28 (d, J= 8.7 Hz, 1H), 8.20 (d, J= 8.4 Hz 1H), 8.02 (d, J =
2H), .8.00 (d, J = 7.8 Hz 1H), 7.84 (dd, J = 9.0, 2.1 Hz, 1H), 7.56-7.52 9.0 Hz, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.78-7.72 (m, 1H), 7.60-7.54 (m,
(m, 1H), 7.48-7.44 (m, 1H); 13C NMR (100 MHz, CDCl3): δ169.27, 1H), 7.43 (d, J = 2.7 Hz, 1H), 7.14 (dd, J = 9.0, 2.7 Hz, 1H), 3.92 (S,
154.12, 151.57, 146.45, 136.42, 136.01, 133.67, 131.35, 129.99, 3H); 13C NMR (75 MHz, CDCl3): δ 167.28, 158.41, 151.50, 148.98,
129.83, 126.45, 126.11, 123.83, 122.06, 121.70, 119.33; HRMS (ESI) 147.93, 138.07, 136.88, 130.02, 129.63, 128.81, 127.71, 127.35,
calculated for C16H9BrN2S (M+H)+ 340.9743; found: 340.9760.
124.36, 118.18, 116.02, 104.17, 55.81; HRMS (ESI) calculated for
2-(Quinoxalin-2-yl)benzo[d]thiazole 3g12. White solid (50%), M.P.: C17H12N2OS (M+H)+ 293.0743; found: 293.0763.
172-174 oC; 1H NMR (300 MHz, CDCl3): δ 9.88 (s, 1H), 8.22-8.15 (m, 6-Methyl-2-(quinolin-2-yl)benzo[d]thiazole 3o15. Yellow solid (70%),
3H), 8.02 (d, J = 7.8 Hz, 1H), 7.86-7.80 (m, 2H), 7.59 (td, J = 7.5, 1.2 M.P.: 210-212 C; 1H NMR (300 MHz, CDCl3): δ 8.53 (d, J = 8.7 Hz,
o
Hz, 1H), 7.51 (td, J= 8.1, 1.2 Hz, 1H); 13C NMR (75 MHz, CDCl3): δ 1H), 8.32 (d, J = 8.4 Hz, 1H), 8.23 (d, J = 8.4 Hz 1H), 8.04 (d, J = 8.4 Hz,
167.15, 154.41, 146.01, 143..23, 142.95, 141.93, 136.31, 131.04, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.78-7.75 (m, 2H), 7.62 (t, J = 7.5Hz, 1H),
130.82, 129.70, 129.50, 126.72, 126.50, 124.23, 122.13; HRMS (ESI) 7.36 (d, J = 8.1 Hz, 1H), 2.53 (S, 3H); 13C NMR (75 MHz, CDCl3): δ
calculated for C15H9N3S (M+H)+ 264.0589; found: 264.0587.
168.77, 152.53, 151.51, 147.94, 136.90, 136.71, 136.17, 130.03,
2-(Isoquinolin-1-yl)benzo[d]thiazole 3h12. White solid (62%), M.P.: 129.72, 128.93, 127.95, 127.70, 127.44, 123.28, 121.72, 118.34,
o
180-182 C; 1H NMR (400 MHz, CDCl3): δ 10.00 (d, J = 8.3 Hz, 1H), 21.61; HRMS (ESI) calculated for C17H12N2S (M+H)+ 277.0794; found:
8.61 (d, J = 5.5 Hz, 1H), 8.20 (d, J = 9.3 Hz, 1H), 7.99 (d, J = 7.9 Hz, 277.0798.
1H), 7.87 (d, J = 7.6 Hz, 1H), 7.79-7.71 (m, 3H), 7.53 (t, J = 7.9 Hz, 6-Ethoxy-2-(quinolin-2-yl)benzo[d]thiazole 3p14. Yellow solid (75%),
o
1H), 7.45 (t, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 170.81, M.P.: 200-202 C; 1H NMR (400 MHz, CDCl3): δ 8.44 (d, J = 8.4 Hz,
154.84, 149.35, 141.76, 137.28, 136.09, 130.48, 129.01, 127.85, 1H), 8.27 (d, J = 8.8 Hz, 1H), 8.19 (d, J = 8.8 Hz 1H), 8.00 (d, J = 9.2 Hz,
126.96, 126.07, 125.90, 124.12, 123.01, 121.64; HRMS (ESI) 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.76-7.72 (m, 1H), 7.58-7.56 (m, 1H),
calculated for C16H10N2S (M+H)+ 263.0637; found: 263.0629.
7.39 (d, J = 2.4 Hz, 1H), 7.11 (dd, J = 8.8, 2.4 Hz 1H), 4.15 (q, J = 6.8
2-(Quinolin-4-yl)benzo[d]thiazole 3i13 white solid (60%), M.P.: 175- Hz 2H), 1.48 (t, J = 6.8 Hz 3H); 13C NMR (100 MHz, CDCl3): δ 167.09,
4 | J. Name., 2012, 00, 1-3
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DOI: 10.1039/C6OB02731H
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157.79, 151.46, 148.80, 147.87, 138.04, 136.95, 130.07, 129.60, 311.0649; found: 311.0669.
ARTICLE
128.81, 127.73, 127.38, 124.33, 118.22, 116.45, 104.82, 64.12, 2-(Isoquinolin-1-yl)-6-methoxybenzo[d]thiazole 3y. yellow
14.85; HRMS (ESI) calculated for C18H14N2OS (M+H)+ 307.09; found: solid (55%), M.P.: 200-202 oC; 1H NMR (300 MHz, CDCl3): δ
307.3960.
9.97-9.94 (m,1H), 8.65 (d, J = 5.4 Hz, 1H), 8.11 (d, J = 9.0 Hz,
4-Methyl-2-(quinolin-2-yl)benzo[d]thiazole 3q. white solid (30%), 1H), 7.93-7.89 (m, 1H), 7.84-7.78 (m, 3H), 7.45 (d, J = 2.4 Hz,
o
M.P.: 172-174 C; 1H NMR (400 MHz, CDCl3): δ 8.57 (d, J = 8.8 Hz, 1H), 7.17 (dd, J = 9.0, 2.4 Hz, 1H), 3.94 (s, 3H); 13C NMR (75
1H), 8.30 (d, J = 8.4 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.0 MHz, CDCl3): δ 158.55, 149.33, 141.33, 137.72, 137.39, 130.69,
Hz, 1H), 7.82 (dd, J = 7.2, 2.0 Hz, 1H), 7.78-7.74 (m, 1H), 7.61-7.57 129.03, 128.04, 126.97, 125.94, 124.77, 122.72, 116.01, 103.73,
(m, 1H), 7.35-7.32 (m, 2H), 2.85 (s, 3H); 13C NMR (100 MHz, CDCl3): 55.83; HRMS (ESI) calculated for C17H12N2OS (M+H)+ 293.0743;
δ 168.32, 153.83, 151.70, 147.94, 136.85, 136.46, 133.92, 130.02, found: 293.0726.
129.74, 128.97, 127.74, 127.44, 126.69, 125.81, 119.40, 118.53,
18.28; HRMS (ESI) calculated for C17H12N2S (M+H)+ 277.0794; found:
Notes and references
277.0796.
6-Chloro-2-(6-methylquinolin-2-yl)benzo[d]thiazole 3t. yellow
solid (60%), M.P.: 212-214 oC; 1H NMR (300 MHz, CDCl3): δ 8.43 (d,
J = 8.7 Hz, 1H), 8.22 (d, J = 8.7 Hz, 1H), 8.12 (d, J = 8.1 Hz 1H), 8.04 (d,
J = 8.7 Hz, 1H), 7.95 (d, J = 1.8 Hz, 1H), 7.63-7.60 (m, 2H), 7.49 (dd, J
= 8.7, 1.8 Hz, 1H), 2.57 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 170.33,
152.85, 149.96, 146.29, 138.11, 137.67, 136.56, 132.69, 131.86,
1.（a）J. Geng, M. Li, L. Wu, J. Ren and X. Qu, J. Med. Chem., 2012,
55, 9146-9155; （b）S. Meghdadi, M. Amirnasr, A. Mirhashemi
and A. Amiri, Polyhedron., 2015, 97, 234-239; （c）C. G.
Mortimer, G. Wells, J.-P. Crochard, E. L. Stone, T. D. Bradshaw,
M. F. Stevens and A. D. Westwell, J. Med. Chem., 2006, 49, 179-
185; （d）R. A. Steiner, D. Foreman, H. X. Lin, B. K. Carney, K.
M. Fox, L. Cassimeris, J. M. Tanski and L. A. Tyler, J. Inorg.
Biochem., 2014, 137, 1-11; （e）X. Wang, K. Sarris, K. Kage, D.
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（f）S. Aiello, G. Wells, E. L. Stone, H. Kadri, R. Bazzi, D. R. Bell,
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129.24, 129.14, 127.13, 126.64, 124.43, 121.62, 118.32, 21.77
HRMS (ESI) calculated for C17H11ClN2S (M+H)+ 311.0404; found:
311.0410.
;
6-Chloro-2-(7-fluoroquinolin-2-yl)benzo[d]thiazole 3u. white solid
o
(40%), M.P.: 224-226 C; 1H NMR (400 MHz, CDCl3): δ 8.44 (d, J =
8.4 Hz, 1H), 8.32 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 8.8 Hz 1H), 7.97 (d, J
= 2.0 Hz, 1H), 7.89-7.81 (m, 2H), 7.50 (dd, J = 8.4, 2.0 Hz, 1H), 7.41
(m, 1H); 13C NMR (100 MHz, CDCl3): δ 169.99, 169.57, 164.75 (d, J =
259.0 Hz), 152.92, 151.91, 148.97 (d, J = 13.0 Hz), 137.78, 137.01,
132.11, 129.80 (d, J = 10.0 Hz), 127.22, 126.05, 124.62, 121.66,
118.39 (d, J = 26.0 Hz), 117.62, 113.41 (d, J = 21.0 Hz); HRMS (ESI)
calculated for C16H8ClFN2S (M+H)+ 315.0154; found: 315.0173.
6-Chloro-2-(isoquinolin-1-yl)benzo[d]thiazole 3v yellow solid (52%),
M.P.: 184-186 oC; 1H NMR (300 MHz, CDCl3): δ 9.35 (m, 1H), 8.66 (d,
J = 5.4 Hz, 1H), 8.13 (d, J = 8.7 Hz 1H),7.99 (d, J = 1.8 Hz, 1H), 7.95-
7.92 (m, 1H), 7.85-7.78 (m, 3H), 7.52 (dd, J = 8.7, 1.8 Hz, 1H); 13C
NMR (75 MHz, CDCl3): δ 171.39, 153.36, 148.87, 141.73, 137.32,
132.03, 130.62, 129.15, 127.65, 127.04, 126.92, 126.01, 124.85,
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Revanna, K. N. Nandeesh, K. Mantelingu and K. S. Rangappa,
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Asemani, Synth. Commun., 2009, 39, 860-867.
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123.28, 121.26;
HRMS (ESI) calculated for C17H9ClN2S (M+H)+
297.0248; found: 297.0230.
6-Methoxy-2-(6-methylquinolin-2-yl)benzo[d]thiazole 3w. yellow
solid (76%), M.P.: 188-200 oC; 1H NMR (300 MHz, CDCl3): δ 8.45 (d,
J = 8.4 Hz, 1H), 8.22 (d, J = 8.7 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.03
(d, J = 9.0 Hz, 1H), 7.62-7.59 (m, 2H), 7.43 (d, J = 2.4 Hz, 1H), 7.15
(dd, J = 9.0, 2.4 Hz, 1H), 3.92 (s, 3H), 2.57 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ 167.01, 158.45, 150.34, 148.68, 146.15, 137.98, 137.76,
136.56, 132.59, 129.06 128.91, 126.65, 124.27, 118.36, 116.15,
104.16, 55.85, 21.74; HRMS (ESI) calculated for C18H14N2OS (M+H)+
307.09; found: 307.0927.
5.（a）G. Evindar and R. A. Batey, J. Org. Chem., 2006, 71, 1802-
1808; （b）D. Ma, S. Xie, P. Xue, X. Zhang, J. Dong and Y. Jiang,
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and J. C. Pelletier, J. Comb. Chem., 2007, 9, 569-570.
2-(7-Fluoroquinolin-2-yl)-6-methoxybenzo[d]thiazole 3x. yellow
solid (69%), M.P.: 201-221 oC; 1H NMR (300 MHz, CDCl3): δ 8.46 (d,
J = 8.4 Hz, 1H), 8.29 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 9.0 Hz, 1H), 7.88-
6. Q. Song, Q. Feng and M. Zhou, Org. Lett., 2013, 15, 5990-5993.
7.81 (m, 2H), 7.43-7.40 (m, 1H), 7.38 (dd, J = 8.7, 2.7 Hz, 1H), 7.16 7. X. Chen, X. Cui, F. Yang and Y. Wu, Org. Lett., 2015, 17, 1445-
(dd, J =9.0, 2.4 Hz, 1H), 3.93 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
1448.
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166.77, 165.11 (d, J = 249.2 Hz), 158.58, 152.34, 148.96 (d, J = 10.6
Hz), 138.11, 136.85, 129.76 (d, J = 9.9 Hz)，125.80，124.43，
118.02 (d, J = 25.4 Hz), 117.62, 117.59, 116.24, 113.33 (d, J = 20.6
Hz), 104.14, 55.85; HRMS (ESI) calculated for C17H11FN2OS (M+H)+
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DOI: 10.1039/C6OB02731H
ARTICLE
10.
Journal Name
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