Insertion Reaction of 2-Halo- N -allylanilines with K 2S Involving Trisulfur Radical Anion: Synthesis of Benzothiazole Derivatives under Transition-Metal-Free Conditions

Article abstract of DOI:10.1055/s-0040-1706104

A synthesis of benzothiazole derivatives through the reaction of 2-halo- N -allylanilines with K ₂S in DMF is developed. The trisulfur radical anion S ₃· ^-, which is generated in situ from K ₂S in DMF, initiates

Full text of DOI:10.1055/s-0040-1706104

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2021, 53, 971–977
paper
971
en
X.-Y. Liu et al.
Paper
Synthesis
Insertion Reaction of 2-Halo-N-allylanilines with K2S Involving
Trisulfur Radical Anion: Synthesis of Benzothiazole Derivatives
under Transition-Metal-Free Conditions
Xin-Yu Liua
Yan-Wei Zhao*a
Tian Jianga
Weidong Raob
Shun-Yi Wang*a
S
R
N
X
K2S, DMF, Ar, 130 °C
H
R
S3
N
H
S
0
0
0
0
-
0
0
0
2
-
8
9
8
5
-8
7
5
3
R
X = I, Br
N
a Key Laboratory of Organic Synthesis of Jiangsu Province, College of
Chemistry, Chemical Engineering and Materials Science & Collabo-
rative Innovation Center of Suzhou Nano Science and Technology,
Soochow University, Suzhou 215123, P. R. of China
ywzhao@suda.edu.cn
yields up to 81%
shunyi@suda.edu.cn
b Nanjing Forest University, Nanjing 210037, P. R. of China
Corresponding Authors
Received: 04.11.2020
Accepted after revision: 19.11.2020
Published online: 14.12.2020
without transition-metal catalysts. Our groups have devel-
oped serial reactions for the construction of different sul-
fur-containing compounds such as benzothiazine (Scheme
1a),9 substituted thiophenes (Scheme 1b),10 as well as 1,2,3-
thiadiazole and isothiazole (Scheme 1c).11
As part of our continuing interests in C–S bond-forma-
tion reactions involving S3·–, we considered whether the re-
action of 2-halo-N-allylanilines with K2S in DMF could be
DOI: 10.1055/s-0040-1706104; Art ID: ss-2020-g0567-op
Abstract A synthesis of benzothiazole derivatives through the reac-
tion of 2-halo-N-allylanilines with K2S in DMF is developed. The trisulfur
radical anion S3·–, which is generated in situ from K2S in DMF, initiates
the reaction without transition-metal catalysis or other additives. In ad-
dition, two C–S bonds are formed and heteroaromatization of benzo-
thiazole is triggered by radical cyclization and H-shift.
Our previous work:
Keywords transition metal-free, trisulfur radical anion, benzothiazole
derivatives, radicals, cyclization
a)
O
O
S
I
K2S, DMF, Ar, 130 °C
S3
N
H
Benzothiazole is a very important skeleton of organic
compounds and it exists in many natural products.1 The
versatile biological activities of benzothiazole compounds
lead to their use as medical and biological molecules,2 and
the importance of benzothiazoles has prompted organic
chemists to focus on their synthesis. Benzothiazoles are
generally obtained by using 2-halobenzothiazole3 and ben-
zo[d]thiazol-2-amine.4 They can also be synthesized by us-
ing aminothiophenol and DMF,5 CO2,6 or CO.7 Although
these methods afford various benzothiazoles, they require
unfriendly reaction conditions, such as precious metal cata-
lysts, complex reaction conditions and multiple steps.
These drawbacks limit the application of these methods in
practice. It is thus desirable to find an environmentally
friendly method for the synthesis of benzothiazoles and
their derivatives.
N
H
b)
S
Ph
Ph
K2S, DMF, Ar, 130 °C
2
Ph
O
Ph
S3
Ph
Ph
N
N
c)
K2S, K2CO3
Et2O, rt
S
TsNHNH2
+
Cl
DMF, 130 °C, air
R
R
S3
This work:
R
S
R
N
X
K2S, DMF, Ar, 130 °C
H
S3
N
H
S
R
X = I, Br
N
S3·– has attracted significant attention for the synthesis
of sulfur-containing compounds in recent years.8 S3·– is eas-
ily generated in situ from K2S or S8 and initiates reactions
Scheme 1 A proposed route to access unsymmetrical thiosulfonates
through insertion of sulfur dioxide
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Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

972
X.-Y. Liu et al.
Paper
Synthesis
used to construct 4H-benzo[b][1,4]thiazine derivatives. To
our surprise, unexpected benzothiazole derivatives were
observed instead of 4H-benzo[b][1,4]thiazine derivatives.
Herein, we offer a new solution for the construction of ben-
zothiazole derivatives via an in situ generated S3·– initiated
reaction of 2-halo-N-allylanilines with K2S in DMF without
transition-metal catalyst or other additives.
The study is initiated by the reaction of 1a (0.5 mmol)
with K2S (2.2 equiv) in DMA (2 mL) at 130 °C under Ar at-
mosphere. To our surprise, 2-ethylbenzo[d]thiazole (3a) in-
stead of 2-methyl-4H-benzo[b][1,4]thiazine was observed
in 24% yield (Table 1, entry 1). To optimize the reaction con-
ditions, we screened the reaction of 1a with K2S in different
solvents such as DMF, DMSO, DCE, CH3CN, and 1,4-dioxane
(entries 2–6). DMF gave the best result and 3a was obtained
in 53% yield. The reaction of 1a with K2S did not afford 3a in
DCE, CH3CN, or 1,4-dioxane. Next, we tried to apply other
sulfur sources to replace K2S (entries 7 and 8); however, it
was found that the reaction of 1a with S8, Na2S2O3 or Cu2S
all failed to give 3a (entries 7, 8, and 16). When Na2S·9H2O
and (NH4)2S instead of K2S were applied to the reaction, 3a
was observed in lower yields (entries 14 and 15). It should
be noted that either increasing or decreasing the amount of
K2S resulted in lower yields of 3a (entries 9 and 10). When
the reaction was carried out under the air atmosphere, no
desired product 3a was observed (entry 11). We also inves-
tigated the effect of temperature (entries 12 and 13) but no
better results were observed.
With the optimized conditions in hand, we explored the
versatility of the reaction; the results are summarized in
Scheme 2. The reaction of N-allyl-4-chloro-2-iodoaniline
(1b) and N-allyl-4-fluoro-2-iodoaniline (1c) with K2S
worked well to afford 3b and 3c in 45% and 42% yield, re-
spectively. Similarly, when N-allyl-2-iodo-4-(trifluoro-
methyl)aniline (1d) and N-allyl-2-iodo-4-methylaniline
(1e) were subjected to the reaction under identical condi-
tions, 3d and 3e was also observed in 46% and 38% yield, re-
spectively. These results indicate that electronic effects at
the 4-position of the aromatic ring has little impact on the
reaction. It should be noted that the reaction of N-allyl-5-
chloro-2-iodoaniline (1f) and N-allyl-5-fluoro-2-iodoani-
line (1g) with K2S also proceeded smoothly to give 3f and
3g in 61% and 66% yields, respectively. The reaction of N-al-
lyl-2-iodo-5-methylaniline (1h) with K2S led to 3h in 51%
yield. Unfortunately, the reactions of 2-iodo-N-(2-methylal-
lyl)aniline (1i), N-(2-bromoallyl)-2-iodoaniline (1j), or 2-
iodo-N-(3-methylbut-2-en-1-yl)aniline (1l) with K2S failed
to furnish the desired products. To our delight, N-cinnamyl-
Table 1 Optimization of the Reaction Conditionsa
I
S
S source, solvent, temp
N
N
H
I
R1
K2S (2.2 equiv), DMF (2 mL)
130 °C, Ar, 12 h
S
N
R2
1a
3a
R2
N
R1
H
3
Yield (%)b
1
Entry
Solvent (2 mL)
S source (equiv)
Temp (°C)
1
2
DMA
DMF
K2S (2.2)
K2S (2.2)
K2S (2.2)
K2S (2.2)
K2S (2.2)
K2S (2.2)
S8 (2.2)
130
130
130
130
130
130
130
130
130
130
130
80
24
F
Cl
S
S
S
N
53
N
N
3
DMSO
DCE
11
3a, 54%
3c, 42%
3b, 45%
4
NR
NR
NR
NR
NR
41
F3C
S
S
N
S
N
5
MeCN
1,4-dioxane
DMF
N
Cl
6
3d, 46%
3f, 61%
3e, 38%
7
S
N
S
N
S
N
8
DMF
Na2S2O3 (1.1)
K2S (2.5)
K2S (1.5)
K2S (2.2)
K2S (2.2)
K2S (2.2)
Na2S.9H2O
(NH4)2S
F
9
DMF
3g, 66%
10
11c
12
13
14
15
16
DMF
trace
NR
NR
trace
32
3i, trace
3h, 51%
DMF
S
Ph
S
S
DMF
N
Br
N
N
DMF
100
130
130
130
3j, trace
3k, 25%
3l, trace
DMF
S
N
DMF
<10
NR
DMF
Cu2S
3m, 44%
a Reaction conditions: 1a (0.5 mmol), solvent (2 mL), 130 °C, 12 h, under Ar
Scheme 2 Substrate scope of 2-iodo-N-allylanilines. Reagents and
conditions: 1 (0.5 mmol), solvent (2 mL), 130 °C, 12 h, under Ar atmo-
sphere. Isolated yields are given.
atmosphere.
b Isolated yield.
c Air atmosphere.
© 2020. Thieme. All rights reserved. Synthesis 2021, 53, 971–977

973
X.-Y. Liu et al.
Paper
Synthesis
Br
I
R1
S
N
K2S (2.2 equiv), DMF (2 mL)
130 °C, Ar, 12 h
R2
K2S, TEMPO (2.0 equiv)
DMF, Ar
S
N
R2
N
H
R1
N
H
2
3
1a
3a, messy
F
Cl
S
Scheme 4 Control experiment
S
N
S
N
N
3c, 76%
3b, 72%
3a, 43%
yield of 3b could be increased from 45% to 72% yield when
N-allyl-2-bromo-4-chloroaniline (2b) instead of 1b was ap-
plied to the reaction with K2S. The reaction of N-allyl-2-
bromo-4-fluoroaniline 2c with K2S gave 3c in 76% yield. It is
worth noting that the reaction conditions were also effi-
cient with N-allyl-2,5-dibromoaniline 2n, which chemose-
lectively afforded 3n in 81% yield. After that, we also tried
the corresponding chlorinated compounds. Although the
corresponding products could be obtained, the reaction
system was rather messy.
S
CF3
S
S
N
Br
N
N
3n, 81%
3e, 41%
3d, 45%
tBu
S
S
N
F
N
3o, 42%
3g, 43%
Scheme 3 Substrate scope of 2-bromo-N-allylanilines. Reagents and
conditions: 1 (0.5 mmol), solvent (2 mL), 130 °C, 12 h, under Ar atmo-
To further understand the reaction mechanism, we
tried the reaction of 1a with K2S in the presence of 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO) (Scheme 4). It was
found that the reaction was complex and no desired prod-
uct 3a was observed. Although it is difficult to confirm
whether formation of S3·– occurred in the TEMPO inhibition
experiment, this result indicated that the in situ generated
S3·– from K2S may be involved and may trigger the reaction.
Based on the above experimental results, and in con-
junction with relevant literature,9 we have proposed a pos-
sible reaction mechanism in Scheme 5. First, S3·– is generat-
sphere. Isolated yields are given.
2-iodoaniline (1k) and (E)-N-(but-2-en-1-yl)-2-iodoaniline
(1m) also reacted with K2S to give 3k and 3m in 25% and
44% yield, respectively.
We then investigated the scope of the reaction with re-
spect to 2-bromo-N-allylanilines under identical reaction
conditions (Scheme 3). It should be noted that the reaction
of 2-bromo-N-allylanilines 2 with K2S could also afford
benzothiazoles but exhibited different reactivities. The
I
I
N
H
N
H
I
1a
I
e–
N
O
yS3
IA
H
O
N
xS2-
N
H
H
II
S3
S
S2
S
S
N
3a
S
S
N
O
N
O
H
IA
H
N
H
IIA
S
N
H
III
N
IV
IX
SH
S
SH
S
N
H
N
H
N
H
N
H
VIII
V
VII
VI
Scheme 5 Plausible mechanism
© 2020. Thieme. All rights reserved. Synthesis 2021, 53, 971–977

974
X.-Y. Liu et al.
Paper
Synthesis
ed in situ by the mixture of K2S in DMF with release of elec-
trons. The electron reacts with 1a to give the radical anion
intermediate I, which releases iodine ion to afford radical II.
The coupling of radical II with S3·– furnishes III, the ho-
molysis of which gives radical IV and S2.–. The latter reacts
with K2S to regenerate S3·–. Following a subsequent 1,5-H
shift, 1,3-H shift and 1,7-H shift, radical IV converts into
radical VII. The intramolecular cyclization of VII leads to
radical VIII. After 1,3-H shift and heteroaromatization, 3a is
formed.
HRMS (ESI): m/z [M + H]+ calcd for C9H9BrClN: 245.9680; found:
245.9685.
N-Allyl-2-bromo-4-fluoroaniline (2c)
Yield: 448 mg (82%); Colorless oil.
1H NMR (300 MHz, CDCl3):  = 7.25–7.18 (m, 1 H), 6.99–6.89 (m, 1 H),
6.59–6.52 (m, 1 H), 5.96 (m, J = 17.2, 10.3, 5.2 Hz, 1 H), 5.34–5.20 (m,
2 H), 4.31 (s, 1 H), 3.80 (m, J = 5.3, 1.7 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 154.6 (d, J = 237.0 Hz), 141.6 (d, J = 2.3
Hz), 134.7, 119.4 (d, J = 24.7 Hz), 116.6, 115.0 (d, J = 21.7 Hz), 111.6 (d,
J = 7.5 Hz), 108.9 (d, J = 9.7 Hz), 46.7.
In summary, a new protocol for the synthesis of benzo-
thiazole derivatives via an in situ generated S3·– initiated re-
action of 2-halo-N-allylanilines with K2S in DMF has been
developed that proceeds under simple reaction conditions
without transition-metal catalyst or other additives. It is in-
teresting that two C–S bonds are formed and heteroaroma-
tization of benzothiazole is triggered by radical cyclization
and H-shift. This study also extends the scope of applica-
tions of S3·– in organic synthesis.
19F NMR (376 MHz, CDCl3):  = –117.1.
HRMS (ESI): m/z [M + H]+ calcd for C9H9BrFN: 229.9975; found:
229.9981.
N-Allyl-2-bromo-5-fluoroaniline (2g)
Yield: 400 mg (73%); Colorless oil.
1H NMR (300 MHz, CDCl3):  = 7.38–7.30 (m, 1 H), 6.39–6.28 (m, 2 H),
5.94 (m, J = 17.2, 10.3, 5.1 Hz, 1 H), 5.35–5.20 (m, 2 H), 4.59 (s, 1 H),
3.81 (m, J = 7.1, 3.4, 2.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 163.4 (d, J = 242.2 Hz), 146.1 (d, J = 11.3
Hz), 134.1, 132.9 (d, J = 9.7 Hz), 116.8, 104.4 (d, J = 22.5 Hz), 103.7 (d,
J = 2.2 Hz), 99.1 (d, J = 27.7 Hz), 46.2.
19F NMR (376 MHz, CDCl3):  = –116.4.
HRMS (ESI): m/z [M + H]+ calcd for C9H9BrFN: 229.9975; found:
Unless otherwise noted, all commercially available compounds were
used as provided without further purification. All the solvents for
routine isolation of products and chromatography were reagent
grade. Analytical thin-layer chromatography (TLC) was performed on
silica gel, with detection by irradiation with UV light. For column
chromatography, 300–400 mesh silica gel was used. 1H and 13C NMR
spectra were recorded with a Bruker 400 MHz and Bruker 300 MHz
spectrometers in CDCl3. Chemical shifts () are reported referenced to
an internal tetramethylsilane standard or to the CDCl3 residual peak
( = 7.26 ppm) for 1H NMR spectra. Chemical shifts of 13C NMR signals
are reported relative to CDCl3 ( = 77.16 ppm). Data are reported as
chemical shift ( in ppm), multiplicity [indicated as s (singlet), bs
(broad singlet), d (doublet), t (triplet), m (multiplet)], coupling con-
stant (J in Hz). Melting points were measured with an Electrothermal
digital melting point apparatus and are uncorrected. IR spectra were
recorded with a Bruker Vertex 70 spectrophotometer and are report-
ed in terms of frequency of absorption (cm–1). HRMS spectra were ob-
tained with a GCT Premier TOF-MS with CI source or with a Bruker
microTOF-Q III instrument with ESI source.
229.9981.
N-Allyl-2-bromo-4-(tert-butyl)aniline (2o)
Yield: 557 mg (87%); Colorless oil.
1H NMR (300 MHz, CDCl3):  = 7.56 (d, J = 2.3 Hz, 1 H), 7.30–7.26 (m, 1
H), 6.70–6.66 (m, 1 H), 6.04 (m, J = 17.2, 10.3, 5.2 Hz, 1 H), 5.42–5.26
(m, 2 H), 4.44 (s, 1 H), 3.89 (m, J = 5.3, 1.7 Hz, 2 H), 1.37 (s, 9 H).
13C NMR (75 MHz, CDCl3):  = 142.5, 141.1, 135.1, 129.4, 125.3, 116.3,
111.4, 109.8, 46.5, 33.9, 31.5.
HRMS (ESI): m/z [M + H]+ calcd for C13H18BrN: 268.0695; found:
268.0701.
N-Allyl-5-chloro-2-iodoaniline (1b)
Yield: 539 mg (77%); Colorless oil.
1H NMR (300 MHz, CDCl3):  = 7.57–7.52 (m, 1 H), 6.53–6.43 (m, 2 H),
6.01–5.88 (m, 1 H), 5.35–5.21 (m, 2 H), 4.4 (s, 1 H), 3.81 (m, J = 5.5, 1.7
Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 147.9, 139.5, 135.6, 133.9, 118.6, 116.9,
110.8, 82.3, 46.5.
Synthesis of 1 and 2 (1a, 2a, 2e,12a 1b, 1d, 1e,12b 1c,12c 1i,12d 1k,12e
1l,12f 1m,12g 2d,12h 2f12i); Typical Procedure for 1a
To a solution of 2-iodoaniline (2.4 mmol) and potassium carbonate
(4.0 mmol) in DMF (3 mL) was slowly added allyl bromide (2.0 mmol).
The mixture was stirred at r.t. for 16 h, then the reaction was
quenched with H2O (15 mL) and the mixture was extracted with EtOAc
(3 × 15 mL). The combined organic layer was dried (MgSO4), filtered
and evaporated, followed by a silica gel column chromatography (PE)
to afford N-allyl-2-iodoaniline.
HRMS (ESI): m/z [M + H]+ calcd for C9H9ClIN: 293.9541; found:
293.9547.
N-Allyl-2-iodo-5-methylaniline (1h)
Yield: 484 mg (74%); Colorless oil.
N-Allyl-2-bromo-4-chloroaniline (2b)
1H NMR (300 MHz, CDCl3):  = 7.60 (d, J = 7.9 Hz, 1 H), 6.47 (d, J = 2.0
Hz, 1 H), 6.40–6.36 (m, 1 H), 6.04 (m, J = 17.2, 10.3, 5.1 Hz, 1 H), 5.41–
5.26 (m, 2 H), 4.34 (s, 1 H), 3.88 (d, J = 5.2 Hz, 2 H), 2.35 (s, 3 H).
13C NMR (75 MHz, CDCl3):  = 146.8, 139.4, 138.6, 134.7, 119.9, 116.4,
111.8, 81.7, 46.6, 21.6.
Yield: 447 mg (76%); Colorless oil.
1H NMR (300 MHz, CDCl3):  = 7.47–7.40 (m, 1 H), 7.18–7.09 (m, 1 H),
6.59–6.50 (m, 1 H), 6.01–5.85 (m, 1 H), 5.34–5.17 (m, 2 H), 4.47 (s, 1
H), 3.81 (d, J = 5.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3):  = 143.6, 134.3, 131.8, 128.4, 121.6, 116.8,
112.1, 109.6, 46.4.
HRMS (ESI): m/z [M + H]+ calcd for C10H12IN: 274.0087; found:
274.0093.
© 2020. Thieme. All rights reserved. Synthesis 2021, 53, 971–977

975
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Synthesis
N-(2-Bromoallyl)-2-iodoaniline (1j)
2-Ethyl-6-fluorobenzo[d]thiazole (3c)
Yield: 419 mg (52%); Colorless oil.
Yield: 38 mg (42%); 68 mg (76%); brown oil.
1H NMR (300 MHz, CDCl3):  = 7.75–7.65 (m, 1 H), 7.26–7.17 (m, 1 H),
6.59–6.49 (m, 2 H), 5.84 (q, J = 1.8 Hz, 1 H), 5.60 (q, J = 1.9 Hz, 1 H),
4.77 (s, 1 H), 4.08 (d, J = 4.3 Hz, 2 H).
IR (neat): 1606, 1567, 1527, 1455, 1248, 1196, 1046, 911, 846, 812,
593 cm–1
1H NMR (400 MHz, CDCl3):  = 7.95–7.83 (m, 1 H), 7.57–7.48 (m, 1 H),
7.22–7.13 (m, 1 H), 3.12 (q, J = 7.6 Hz, 2 H), 1.46 (t, J = 7.6 Hz, 3 H).
.
13C NMR (75 MHz, CDCl3):  = 145.8, 139.2, 130.1, 129.5, 119.7, 116.8,
111.1, 85.4, 52.2.
13C NMR (100 MHz, CDCl3):  = 173.3 (d, J = 4.3 Hz), 160.3 (d, J = 243.5
Hz), 150.0, 136.1 (d, J = 12.6 Hz), 123.4 (d, J = 9.4 Hz), 114.5 (d, J = 24.4
Hz), 107.9 (d, J = 27.5 Hz), 27.9, 13.8.
HRMS (ESI): m/z [M + H]+ calcd for C9H9IBrN: 337.9036; found:
337.9041.
19F NMR (376 MHz, CDCl3):  = –117.1.
HRMS (ESI): m/z [M + H]+ calcd for C9H8NSF: 182.0434; found:
N-Allyl-5-fluoro-2-iodoaniline (1g)
Yield: 423 mg (64%); Colorless oil.
182.0436.
1H NMR (400 MHz, CDCl3):  = 7.60–7.54 (m, 1 H), 6.32–6.20 (m, 2 H),
6.00–5.89 (m, 1 H), 5.35–5.21 (m, 2 H), 4.45 (s, 1 H), 3.81 (m, J = 5.5,
1.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3):  = 164.5 (d, J = 181.5 Hz), 148.6 (d, J = 9.0
Hz), 139.4 (d, J = 7.5 Hz), 134.0, 116.9, 105.6 (d, J = 17.3 Hz), 98.5 (d, J =
20.2 Hz), 77.9 (d, J = 2.2 Hz), 46.5.
Ethyl-6-(trifluoromethyl)benzo[d]thiazole (3d)
Yield: 53 mg (46%); 52 mg (45%); yellow oil.
IR (neat): 1581, 1415, 1315, 1275, 1161, 1115, 1081, 1048, 881, 826,
720, 646 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.16–8.10 (m, 1 H), 8.07–8.00 (m, 1 H),
7.73–7.65 (m, 1 H), 3.18 (q, J = 7.6 Hz, 2 H), 1.48 (t, J = 7.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3):  = 177.1, 155.4, 135.3, 127.1 (q, J = 32.3
Hz), 124.4 (q, J = 270.8 Hz), 123.1 (d, J = 38.0 Hz), 123.0, 119.3 (d, J =
23.0 Hz), 28.1, 13.7.
19F NMR (376 MHz, CDCl3):  = –112.2.
HRMS (ESI): m/z [M + H]+ calcd for C9H9IFN: 277.9836; found:
277.9842.
Benzothiazole Derivatives 3; General Procedure
19F NMR (376 MHz, CDCl3):  = –61.35.
In a Schlenk tube, 1 or 2 (0.5 mmol), and K2S (2.2 equiv) and were
added and the tube was charged with argon three times. DMF (2.0
mL) was then added and the mixture was stirred at 130 °C for 12
hours. After the mixture was cooled to r.t., the reaction was quenched
with H2O (15 mL) and the mixture was extracted with EtOAc (3 × 15
mL). The combined organic layer was dried (MgSO4), filtered and
evaporated followed by a silica gel column chromatography (EtOAc/PE
= 1:100) to afford product 3.
HRMS (ESI): m/z [M + H]+ calcd for C10H8NSF3: 232.0402; found:
232.0405.
Ethyl-6-methylbenzo[d]thiazole (3e)
Yield: 34 mg (38%); 36 mg (41%); yellow oil.
IR (neat): 1605, 1523, 1457, 1377, 1304, 1277, 1165, 1054, 948, 811,
586 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.87–7.81 (m, 1 H), 7.65–7.61 (m, 1 H),
7.28–7.23 (m, 1 H), 3.12 (q, J = 7.6 Hz, 2 H), 2.47 (s, 3 H), 1.46 (td, J =
7.6, 0.7 Hz, 3 H).
Ethylbenzo[d]thiazole (3a)
Yield: 44 mg (54%); 36 mg (43%); brown oil.
13C NMR (100 MHz, CDCl3):  = 172.6, 151.5, 135.3, 134.7, 127.5,
122.1, 121.4, 27.8, 21.5, 13.9.
IR (neat): 1519, 1455, 1434, 1309, 1277, 1238, 1124, 946, 755, 727,
706 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.01–7.92 (m, 1 H), 7.87–7.79 (m, 1 H),
7.48–7.39 (m, 1 H), 7.39–7.30 (m, 1 H), 3.15 (q, J = 7.6 Hz, 2 H), 1.47 (t,
J = 7.6 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C10H11NS: 178.0685; found:
178.0681.
13C NMR (100 MHz, CDCl3):  = 173.7, 153.4, 135.2, 126.0, 124.7,
5-Chloro-2-ethylbenzo[d]thiazole (3f)
122.6, 121.6, 27.9, 13.9.
HRMS (ESI): m/z [M + H]+ calcd for C9H9NS: 164.0528; found:
164.0531.
Yield: 60 mg (61%); brown solid; mp 46–47 °C.
IR (neat): 1724, 1658, 1579, 1503, 1453, 1435, 1284, 1174, 1070, 948,
902, 797, 769, 731, 631 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.94 (d, J = 2.0 Hz, 1 H), 7.74 (d, J = 8.5
Hz, 1 H), 7.32 (dd, J = 8.5, 2.0 Hz, 1 H), 3.14 (q, J = 7.6 Hz, 2 H), 1.46 (t,
J = 7.6 Hz, 3 H).
6-Chloro-2-ethylbenzo[d]thiazole (3b)
Yield: 44 mg (45%); 71 mg (72%); brown solid; mp 45–46 °C.
13C NMR (100 MHz, CDCl3):  = 175.7, 154.3, 133.5, 132.0, 125.2,
122.6, 122.3, 28.0, 13.8.
IR (neat): 1616, 1592, 1519, 1480, 1436, 1397, 1299, 1268, 1168,
1049, 857, 813, 700 cm–1
.
1H NMR (400 MHz, CDCl3):  = 7.87–7.83 (m, 1 H), 7.80–7.77 (m, 1 H),
7.42–7.36 (m, 1 H), 3.16–3.09 (m, 2 H), 1.45 (t, J = 7.6 Hz, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C9H8NSCl: 198.0139; found:
198.0145.
13C NMR (100 MHz,CDCl3):  = 174.2, 151.9, 136.4, 130.6, 126.8, 123.3,
121.2, 27.9, 13.7.
2-Ethyl-5-fluorobenzo[d]thiazole (3g)
HRMS (ESI): m/z [M + H]+ calcd for C9H8NSCl: 198.0139; found:
Yield: 60 mg (66%); 39 mg (43%); yellow oil.
198.0137.
IR (neat): 1606, 1567, 1515, 1454, 1308, 1266, 1147, 1123, 1049, 957,
856, 797, 693, 624 cm–1
.
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X.-Y. Liu et al.
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Synthesis
1H NMR (400 MHz, CDCl3):  = 7.79–7.71 (m, 1 H), 7.67–7.60 (m, 1 H),
7.16–7.08 (m, 1 H), 3.14 (q, J = 7.6 Hz, 2 H), 1.46 (t, J = 7.6 Hz, 3 H).
(tert-Butyl)-2-ethylbenzo[d]thiazole (3o)
Yield: 46 mg (42%); brown oil.
13C NMR (100 MHz, CDCl3):  = 176.4, 161.8 (d, J = 59.4 Hz), 154.3 (d,
J = 11.3 Hz), 129.3 (d, J = 10.3 Hz), 122.2 (d, J = 10.2 Hz), 113.4 (d, J =
25.4 Hz), 108.9 (d, J = 2.5 Hz), 28.0, 13.8.
19F NMR (376 MHz, CDCl3):  = –116.4.
HRMS (ESI): m/z [M + H]+ calcd for C9H8NSF: 182.0434; found:
IR (neat): 1727, 1574, 1517, 1455, 1396, 1377, 1313, 1275, 1170,
1072, 1045, 963, 780, 726 cm–1
1H NMR (400 MHz, CDCl3):  = 7.91–7.86 (m, 1 H), 7.84–7.81 (m, 1 H),
7.53–7.48 (m, 1 H), 3.12 (q, J = 7.6 Hz, 2 H), 1.45 (t, J = 7.6 Hz, 3 H),
1.38 (s, 9 H).
.
13C NMR (100 MHz, CDCl3):  = 173.0, 151.3, 148.1, 135.2, 124.1,
182.0436.
121.9, 117.7, 35.0, 31.7, 27.8, 14.0.
2-Ethyl-5-methylbenzo[d]thiazole (3h)
HRMS (ESI): m/z [M + H]+ calcd for C13H17NS: 220.1154; found:
Yield: 45 mg (51%); yellow oil.
220.1142.
IR (neat): 1728, 1607, 1518, 1455, 1305, 1155, 1063, 1002, 947, 827,
795, 611.
Funding Information
1H NMR (400 MHz, CDCl3):  = 7.80–7.74 (m, 1 H), 7.72–7.66 (m, 1 H),
7.19–7.12 (m, 1 H), 3.12 (q, J = 7.6 Hz, 2 H), 2.48 (s, 3 H), 1.45 (t, J = 7.6
Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 173.7, 153.8, 136.0, 132.05, 126.3,
122.6, 121.1, 27.9, 21.5, 13.9.
We gratefully acknowledge the National Natural Science Foundation
of China (21971174 and 21772137), PAPD, the Major Basic Research
Project of the Natural Science Foundation of the Jiangsu Higher Edu-
cation Institutions (No. 16KJA150002), the Project of Scientific and
Technologic Infrastructure of Suzhou (SZS201708), Soochow Univer-
sity, and State and Local Joint Engineering Laboratory for Novel Func-
HRMS (ESI): m/z [M + H]+ calcd for C10H11NS: 178.0685; found:
178.0685.
tional Polymeric Materials for financial support.
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2-Phenethylbenzo[d]thiazole (3k)
Yield: 30 mg (25%); yellow oil.
Acknowledgment
IR (neat):1602, 1519, 1454, 1435, 1312, 1243, 1189, 1062, 1014, 758,
729, 699 cm–1
.
Dedicated to the 120th anniversary of Soochow University.
1H NMR (400 MHz, CDCl3):  = 8.11–7.97 (m, 1 H), 7.91–7.84 (m, 1 H),
7.52–7.46 (m, 1 H), 7.42–7.38 (m, 1 H), 7.38–7.27 (m, 5 H), 3.47 (dd,
J = 9.2, 6.9 Hz, 2 H), 3.25 (dd, J = 9.4, 6.7 Hz, 2 H).
Supporting Information
13C NMR (100 MHz, CDCl3):  = 171.1, 153.3, 140.3, 135.3, 128.7,
128.6, 126.6, 126.1, 124.9, 122.7, 121.7, 36.1, 35.7.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1706104.
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HRMS (ESI): m/z [M + Na]+ calcd for C15H13NS: 262.0661; found:
262.0664.
References
2-Propylbenzo[d]thiazole (3m)
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727 cm–1
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1H NMR (400 MHz, CDCl3):  = 8.00–7.94 (m, 1 H), 7.86–7.80 (m, 1 H),
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(m, 2 H), 1.05 (t, J = 7.4 Hz, 3 H).
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122.6, 121.6, 36.4, 23.2, 13.8.
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178.0684.
5-Bromo-2-ethylbenzo[d]thiazole (3n)
Yield: 99 mg (81%); brown solid; mp 45–46 °C.
IR (neat): 1575, 1593, 1501, 1451, 1432, 1405, 1298, 1255, 1173,
1052, 950, 890, 795, 628, 603 cm–1
.
1H NMR (400 MHz, CDCl3):  = 8.13–8.08 (m, 1 H), 7.70–7.64 (m, 1 H),
7.46–7.41 (m, 1 H), 3.17–3.10 (m, 2 H), 1.45 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3):  = 175.5, 154.6, 134.0, 127.8, 125.5,
122.6, 119.5, 27.9, 13.8.
HRMS (ESI): m/z [M + H]+ calcd for C9H8NSBr: 241.9634; found:
241.9633.
© 2020. Thieme. All rights reserved. Synthesis 2021, 53, 971–977

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Synthesis
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© 2020. Thieme. All rights reserved. Synthesis 2021, 53, 971–977