Acid-Catalyzed Synthesis of Aryl[4,5]isothiazoles through a Sulfenic Acid Pathway

Article abstract of DOI:10.1055/s-0039-1690201

A new method to efficiently prepare 3-substituted aryl[4,5]isothiazoles by simply heating the starting materials with a catalytic amount of p -toluenesulfonic acid in toluene is reported. This simple procedure is well suitable for a variety of substrates

Full text of DOI:10.1055/s-0039-1690201

SYNLETT
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©
Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
letter
A
en
Synlett
H. Yuan, Z. Sun
Letter
Acid-Catalyzed Synthesis of Aryl[4,5]isothiazoles through a
Sulfenic Acid Pathway
R2
R2
Hong Yuan
catalyzed by 0.2 equiv TsOH
NH2
Zhihua Sun*
R1
Ar
R1 Ar
N
S
O
S
60 °C, 1 h, toluene
College of Chemistry and Chemical Engineering, Shanghai University
of Engineering Science, 333 Longteng Road, Shanghai 201620,
P. R. of China
Green procedure
Mild reaction conditions
High functional group tolerance
18 examples
up to 68–92% isolated yield
R1 = H, aromatic ring,
sungaris@gmail.com
halogen, alkoxy
R2 = aromatic ring,
aromatic heterocycle,
alkane
3
Received: 03.08.2019
Accepted after revision: 22.08.2019
Published online: 05.09.2019
pound 3 is a pesticide, and compounds 4, 5, and 6 are po-
4
tent inhibitors of biological targets/pathways. Isothiazoles
DOI: 10.1055/s-0039-1690201; Art ID: st-2019-l0408-l
represent an important class of five-membered sulfur het-
erocycles that are widely utilized in medicinal chemistry
and organic synthesis because of their unique properties:
They contain two electronegative heteroatoms in a 1,2-rela-
Abstract A new method to efficiently prepare 3-substituted
aryl[4,5]isothiazoles by simply heating the starting materials with a cat-
alytic amount of p-toluenesulfonic acid in toluene is reported. This sim-
ple procedure is well suitable for a variety of substrates that can tolerate
substitution changes in the fusing aromatic ring, as well as at the 3-po-
sition. Substituted aryl rings of varying electronic properties and alkyl
substitution eventually afford aryl[4,5]isothiazoles in high yields.
5
tionship. Therefore, the development of a synthetic meth-
od for the construction of isothiazole moieties is of great re-
search interest. Among the reported methods, there are a
few that can easily manipulate the substitution at the 3-po-
sition of aryl[4,5]isothiazole. McKinnon and Lee reported a
Key words 3-substituted aryl[4,5]isothiazoles, p-toluenesulfonic acid,
fused aromatic rings, catalytic reactions, synthetic methods
condensation method of the oximes of 2-acylthisoanisoles
6
(
Scheme 1). Devarie-Baez and Xian described a procedure
that proceeds through S-nitrosation of o-mercaptoacylphe-
7
The isothiazole moiety can be found in many com-
pounds useful for biomedical research and for medical and
agricultural use. For example, as shown in Figure 1, com-
pounds 1 and 2 are approved by the U.S. Food and Drug
Administration (FDA) for treatment of schizophrenia; com-
nones. We also reported an all-heteroatom Wittig-equiva-
lent procedure that uses tert-butyl sulfoxide as the sulfinyl
8
source. In continuing our investigation for the synthesis of
1
2
3-substituted aryl[4,5]isothiazoles, here we report a new
procedure that avoids the use of NBS as activating reagent.
F
F
O
F
S
HN
N
N
N
N
N
S
S
N
N
N
Cl
S
ziprasidone
antipsychotic medicine
1
lurasidone
antipsychotic medicine
2
pesticide
3
H3CO
H3CO
N
N
O
N
HN
N
S
O
N
O
N
H3CO
S
N
S
N
H
stimulating neurogenesis agent
4
GABAA/BzR ligand
5
GAK inhibitor
6
Figure 1 Selected examples of bioactive molecules that contain the isothiazole moiety
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synlett
H. Yuan, Z. Sun
Letter
R2
R2
In our previous NBS-based procedure we used two
OH
equivalents of NBS to activate tert-butyl sulfoxide to form a
reactive sulfinyl bromide. However, we also noticed that
N
N
AcOH
R1
(
a) R1 Ar
ref. 6
Ar
N
9
S
S
C6H6N, 90 °C, 10 h
thermolysis of tert-butyl sulfoxide could lead to sulfenic
acid that can act as an electrophile.10 Zhang et al. described
R2
R2
11
S
a procedure that proceeds by tert-butyl suifide. We there-
O
(
(
(
b) R1 Ar
H
O
NBS, AcOH, CH2Cl2
R1 Ar
fore reasoned that the thermolysis procedure may allow us
to find conditions that avoid the use of NBS for activation,
and allow direct formation of the N–S bond to form the iso-
thiazole ring by using amine as the nucleophile. To test this
idea, we performed a model reaction under different heat-
ing conditions and the results are shown in Table 1.
The transformation of 7b to 9b was then optimized with
regard to reagent ratio, acid used, and solvent. The results
are summarized in Table 1. Thermolysis without acid pro-
vided the desired product but the reaction time was long
(10 h, entry 1). Use of varying amounts of acetic acid and
heating in toluene at high temperatures allowed to effec-
tively obtain the desired product in good yields (about 82%)
with reduced reaction time; lower temperatures were not
useful conditions (entries 2–5). Changing the acid from ace-
tic acid to tosylic acid led to better results with lower tem-
N
S
r.t., 20 min
S
ref. 8
R2
S
R2
O
NH2OH, NaOH, HCl, H2O
c) R1 Ar
R1 Ar
N
AcOH, Ac2O, 100 °C, 0.5 h
S
ref. 11
R2
R2
N
NH2 catalyzed by 0.2 equiv TsOH
O
d) R1 Ar
R1
Ar
S
S
6
0 °C, 1 h, toluene
7
This work
9
Scheme 1 Methods for the synthesis of aryl[4,5]isothiazoles
Table 1 Exploration of Optimal Conditions for a Model Reactiona
Ph
Ph
NH
Ph
N
NH2 acid, solvent
O
Temp, h
S
S
S
7b
8
9b
Entry
Acid
AcOH
Solventb
Reagent ratio (7b/acid)
Temp (°C)/time (h)
Yield of 9b or (8) (%)c
1
2
3
4
5
6
7
8
9
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
1.0/0
90/10
60/12
90/6
90/6
35/2
35/2
60/1
90/2
60/1
60/1
60/1
40/2
60/1
60/1
60/1
60/1
81
AcOH
AcOH
AcOH
AcOH
TsOH
1.0/0.2
1.0/0.2
1.0/1.5
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
1.0/0.2
42 (40)
83
82
0 (0)
0 (25)
88
TsOH
TsOH
78
TFA
30 (12)
33 (47)
28 (4)
23 (6)
47 (2)
33 (4)
39 (16)
62 (2)
1
1
1
1
1
1
0
1
2
3
4
5
6
benzoic acid
2 4
H SO
TsOH
TsOH
TsOH
TsOH
TsOH
CH
THF
CH CN
2
Cl
2
3
EtOH
DMF
1
a
Reaction conditions: To a solution of 7b (1 mmol) in solvent (3 mL) was added acid (0.2 mmol) in solvent (2 mL) at different temperatures. The mixture was
stirred under those conditions for another 1 h.
b
Purified solvent.
Isolated yield.
c
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

C
Synlett
H. Yuan, Z. Sun
Letter
R2
with use of CH Cl , THF, CH CN, EtOH, or DMF). Therefore,
2 2 3
R2
one hour of heating at 60 °C in toluene with 0.2 equivalents
of tosylic acid was chosen as the standard conditions for
further investigation. It was notable that product 8 can be
isolated as well during the above investigations at various
conditions except those that gave more than 80% of the fi-
nal product 9b.
NH2
O
R1 Ar
1) 0.2 equiv TsOH, toluene
) 60 °C, 1 h
S
R1 Ar
N
2
S
7
9
OCH3
CF3
Using the standard conditions, we tested our protocol
N
with a range of substrates. The results are summarized in
N
N
N
N
N
12,13
Scheme 2.
The first example was the formation of the
S
S
S
S
S
parent benzoisothiazole and 92% isolated yield was ob-
tained. The next seven examples contain different aromatic
rings at the 3-position, and all produced excellent isolated
yields (81–91%, products 9b–h). It seems that both elec-
tron-withdrawing and -donating groups at the 3-aryl sub-
stitution were well tolerated. The next five examples ex-
plored the substitution on the fused aromatic ring, and its
combination with an electron-rich 3-aryl (furan) or a 3-
9
a (92%)
9b (88%)
9c (90%)
9d (83%)
9e (91%)
N
O
N
S
N
N
N
H3CO
S
S
S
9f (85%)
9g (86%)
9h (81%)
9i (73%)
CF3
O
phenyl with an electron-withdrawing group (CF ). Again,
3
F
H3CO
H3CO
N
good isolated yields were obtained in those cases (73–83%,
products 9i–m). Additionally, 3-alkyl- or alkenyl-substitut-
ed examples were studied, and our method still produced
very good isolated yields (68–90%, 9n–r).
N
N
N
S
S
S
S
9
j (83%)
9k (75%)
9l (81%)
9m (78%)
A tentative mechanism has been proposed (as Scheme 3
shows). The reaction proceeds through initial reaction of 7a
with 0.2 equivalents of p-toluenesulfonic acid to afford
complex C. Then, sulfonamide exchange might occur with
substrate 7a to generate 8a and complex A (conformed by
N
S
N
S
N
N
N
S
S
S
9
n (78%)
9o (87%)
9p (89%)
9q (90%)
9r (68%)
Scheme 2 Results with expanded substrate scope
1
H NMR spectroscopy). Complex A converts into complex B
peratures and short reaction times (entries 6–8, best condi-
tions in entry 7). Other acids in the toluene solvent system
were not so effective (entries 9–11). Use of other solvents
in combination with TsOH gave lower yields (entries 12–16
(confirmed by LCMS-IT-TOF, HRMS (ESI-TOF): m/z [M + H]+
calcd for C H NO S H: 310.0537; found: 310.0532)
14
15
3 2
through the loss of a stable tert-butyl cation which in turn
produces gaseous isobutene and one proton. Furthermore,
NH2
O
S
TsOH
(
initial reaction)
7a
O
S
O
S
[O]
N
O
N
N
NH
+
H
O
S
O
S
S
S
9a
8a
A
H2O
O
S
O
N
+
H
H
S
OH
B
Scheme 3 Proposed reaction pathway
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

D
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H. Yuan, Z. Sun
Letter
1
the above complex B releases of one molecule of water to
afford complex C. Then, molecular aromatization of 8a
forms 9a and complex C can be recycled.
H NMR (400 MHz, CDCl ):  = 7.81–7.79 (m, 1 H), 7.50–7.38 (m,
3
3
H), 4.18 (d, J = 14.5 Hz, 1 H), 3.74 (d, J = 14.5 Hz, 1 H), 1.72 (s, 2
13
1
H), 1.16 (s, 9 H). C{ H} NMR (101 MHz, CDCl ):  = 142.9,
1
3
38.0, 131.5, 128.1, 127.3, 126.4, 57.4, 42.7, 23.0.
In summary, using an acid-catalyzed thermolysis proce-
dure, we identified a new method to efficiently prepare 3-
substituted aryl[4,5]isothiazoles by simply heating the
starting materials with a catalytic amount of p-toluenesul-
fonic acid in toluene without using NBS. This simple proce-
dure is well suitable for a variety of substrates that can tol-
erate substitution changes in the fusing aromatic ring, as
well as at the 3-position with substituted aryl rings of vary-
ing electronic properties and alkyl substitutions. Especially,
this is the first time we have found that sulfenic acid can be
formed from sulfoxide under the catalysis of p-toluenesul-
fonic acid and relatively mild conditions. Further intramo-
lecular ring closure products can be synthesized easily. The
[
2-(tert-Butylsulfinyl)phenyl](4-trifluoromethylphenyl)-
methanamine (7d): eluent PE/EtOAc (1:9, v/v), colorless oil;
yield: 255 mg (72%). H NMR (400 MHz, CDCl ):  = 7.87−7.84
(m, 1 H), 7.65−7.62 (m, 1 H), 7.60−7.53 (m, 4 H), 7.50−7.42 (m, 2
H), 5.82 (s, 1 H), 1.82 (s, 2 H), 1.31 (s, 9 H). C{ H} NMR (101
MHz, CDCl ):  = 147.0, 145.6, 138.6, 131.9, 129.7, 129.4, 128.0,
1
MHz, CDCl ):  = –62.42 (s). HRMS (ESI-TOF): m/z [M + H] calcd
for C18H20NF SH: 356.4072; found: 356.4069.
1
3
13
1
3
19
27.3, 125.3 (q, J = 3.7 Hz), 122.7, 57.5, 53.9, 23.3. F NMR (376
+
3
3
[
2-(tert-Butylsulfinyl)phenyl](1-methyl-1H-pyrrol-2-
yl)methanamine (7g): eluent PE/EtOAc (1:9, v/v), purple red
oil; yield: 230 mg (84%). H NMR (400 MHz, CDCl ):  =
7.90−7.87 (m, 1 H), 7.53−7.46 (m, 3 H), 6.55−6.54 (m, 1 H),
6
1
3
.07−6.02 (m, 2 H), 5.62 (s, 1 H), 3.52 (s, 3 H), 1.93 (s, 2 H), 1.32
13
1
(s, 9 H). C{ H} NMR (101 MHz, CDCl ):  = 144.2, 138.0, 136.1,
3
“green” aspect of this procedure will make it a good supple-
1
3
31.7, 127.7, 127.4, 126.4, 123.0, 106.7 (d, J = 2.2 Hz), 57.0, 48.2,
ment to existing methodologies.
+
4.3, 23.4. HRMS (ESI-TOF): m/z [M
+
Na] calcd for
C16H22N OSNa: 313.1345; found: 313.1341.
2
[
2-(tert-Butylsulfinyl)-4-methoxyphenyl](phenyl)methan-
Funding Information
amine (7i): eluent PE/EtOAc (1:9, v/v), white solid; yield: 236
mg (83%). H NMR (400 MHz, CDCl ):  = 7.58−7.56 (m, 1 H),
7
2
1
3
We gratefully thank the financial support from the Science and Tech-
nology Commission of Shanghai Municipality (17ZR1412000).
.44 (t, J = 8.1 Hz, 1 H), 7.37 (d, J = 7.9 Hz, 2 H), 7.29−7.26 (m,
H), 7.19 (d, J = 7.3 Hz, 1 H), 6.97 (d, J = 7.9 Hz, 1 H), 5.57 (s, 1
S
c
i
e
n
c
e
a
n
d
T
e
c
h
n
o
l
o
g
y
C
o
m
m
i
si
o
n
of
S
h
a
n
g
h
a
iM
u
n
i
c
i
p
a
l
i
ty (1
7
Z
R
1
4
1
2
0
0
0)
13
1
H), 3.62 (s, 3 H), 2.27 (s, 3 H), 1.33 (s, 9 H). C{ H} NMR (101
MHz, CDCl ):  = 157.7, 144.3, 139.8, 133.5, 128.6, 128.3, 127.9,
Supporting Information
3
1
27.6, 126.3 (d, J = 8.5 Hz), 125.9 (d, J = 19.4 Hz), 118.6, 114.8,
+
Supporting information for this article is available online at
57.3, 55.7, 53.6, 23.3. HRMS (ESI-TOF): m/z [M + Na] calcd for
https://doi.org/10.1055/s-0039-1690201.
S
u
p
p
orti
n
g Inform ati
o
n
S
u
p
p
orit
n
g Inform ati
o
n
C
18
H
23NO
2
SNa: 340.1342; found: 340.1340.
[
2-(tert-Butylsulfinyl)-5-methoxyphenyl](furan-2-yl)meth-
anamine (7l): eluent PE/EtOAc (1:9, v/v), white solid; yield: 265
1
References and Notes
mg (80%). H NMR (400 MHz, CDCl
7
3
):  = 7.75 (d, J = 8.8 Hz, 1 H),
.33 (d, J = 2.6 Hz, 1 H), 7.16−7.15 (m, 1 H), 6.70−6.97 (m, 1 H),
6.27−6.26 (m, 1 H), 6.03 (d, J = 3.2 Hz, 1 H), 3.84 (s, 3 H), 3.17 (s,
2 H), 2.01 (s, 1 H), 1.25 (s, 9 H). 13C{
H} NMR (101 MHz, CDCl ):
 = 162.3, 156.2, 144.4, 142.2, 128.7, 128.5, 113.8, 112.4, 110.3,
106.5, 56.9, 55.5, 49.2, 23.1. HRMS (ESI-TOF): m/z [M + Na]
calcd for C16H21NO SNa: 330.1134; found: 330.1133.
[2-(tert-Butylsulfinyl)-5-methoxyphenyl](4-trifluoro-
methyl-phenyl)methanamine (7m): eluent PE/EtOAc (1:9,
v/v), colorless oil; yield: 288 mg (83%). H NMR (400 MHz,
(1) (a) Busch, F. R.; Rose, C. A. Patent US6110918, 1995. (b) Stahl, S.
M.; Shayegan, D. K. J. Clin. Psychiatry 2003, 64, Suppl. 19: 6–12.
2) (a) George, M.; Amrutheshwar, R.; Rajkumar, R. P.; Kattimani,
S.; Dkhar, S. A. Eur. J. Clin. Pharmacol. 2013, 69, 1497. (b) Osaka,
M. N.; Osaka, M. O.; Osaka, S. S. Patent US9174975, 2003.
3) Huebl, D.; Pieroh, E. Patent DE 3837578 A1, 1990.
4) (a) Clarksville, J. K. A. Patent US8609840 B2, 2008. (b) Nielsen,
M.; Liljefors, T.; Nilsson, J.; Sterner, O. Patent WO 2009123536
A1, 2009. (c) Dejonghe, S.; Herdewyn, P.; Bekerman, E.; Einav,
S.; Neveu, G. Patent WO 2016012536 A1, 2016.
1
3
(
+
3
(
(
1
CDCl ):  = 7.78 (d, J = 8.8 Hz, 1 H), 7.61−7.54 (m, 4 H), 7.17 (d,
3
J = 2.6 Hz, 1 H), 6.98−6.95 (m, 1 H), 5.81 (s, 1 H), 3.83 (s, 3 H),
(5) Ana, D. O. S.; James, M.; Michal, S. Adv. Synth. Catal. 2019, 361,
1.94 (s, 2 H), 1.29 (s, 9 H). 13C{
H} NMR (101 MHz, CDCl ):
3
1
3050.
 = 162.5, 158.3, 147.0, 138.8, 134.8, 128.9, 125.8 (q, J = 3.8 Hz),
(6) McKinnon, D. M.; Lee, K. R. Can. J. Chem. 1988, 66, 1405.
(7) Devarie-Baez, N. O.; Xian, M. Org. Lett. 2010, 12, 752.
(8) Xu, F.; Chen, Y.; Fan, E.; Sun, Z. Org. Lett. 2016, 18, 2777.
(9) Wei, J. H.; Sun, Z. Org. Lett. 2015, 17, 5396.
120.7, 119.3, 104.8, 55.7. 19F NMR (376 MHz, CDCl ):  = −62.49
3
+
(s). HRMS (ESI-TOF): m/z [M + Na]
408.1216; found: 408.1214.
1-[2-(2-Methyl-propane-2-sulfinyl)-phenyl]-allylamine (7r):
eluent PE/EtOAc (1:9, v/v), colorless liquid; yield: 226 mg (65%).
calcd for C19H22F NO SNa:
3 2
(10) Wu, S.; Lei, X.; Fan, E.; Sun, Z. Org. Lett. 2018, 20, 522.
(11) Zhang, X.; Nirschl, A. A.; Zou, Y.; Priestley, E. S. PCT Int. Appl
1
H NMR (400 MHz, CDCl ):  = 7.80−7.78 (m, 1 H), 7.53−7.51 (m,
3
2007002313, 2007.
1 H), 7.48−7.45 (m, 1 H), 7.44−7.37 (m, 1 H), 5.96−5.88 (m, 1 H),
5.17 (d, J = 17.1 Hz, 1 H), 5.06−5.03 (m, 2 H), 1.74 (s, 2 H), 1.22
(
12) To a solution of 7 (1 equiv) in toluene (3 mL) TsOH (0.2 equiv)
in toluene (2 mL) was added. The mixture was stirred at 60 °C
for 1 h. Then the reaction mixture was cooled to room tempera-
ture and concentrated. The residue was loaded on a silica gel
using petroleum ether/ethyl acetate (20:1) to afford the desired
product 9.
(s, 9 H). 13C{
H} NMR (101 MHz, CDCl ):  = 144.3, 141.2, 137.5,
3
1
131.6, 127.5, 126.4 (d, J = 19.7 Hz), 114.2, 56.9, 53.2, 23.1. HRMS
(ESI-TOF): m/z [M + Na]
found: 260.1076.
+
calcd for C13H19NOSNa: 260.1080;
3-Naphthalen-2-yl-benzo[d]isothiazole (9f): eluent PE/EtOAc
(20:1, v/v), colorless oil; yield: 132 mg (85%). H NMR (400 MHz,
CDCl ):  = 8.39 (s, 1 H), 8.32 (d, J = 8.2 Hz, 1 H), 8.06 (d, J = 7.7
(13) Characterization data of new compounds
1
(2-Methyl-propane-2-sulfinyl)-benzylamine (7a): eluent
3
CH Cl /MeOH (10:1, v/v), yellow oil; yield: 645 mg (61%).
Hz, 3 H), 8.02−7.92 (m, 2 H), 7.60 (m, 3 H), 7.53 (m, 1 H). 13C{
1
H}
2
2
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E

E
Synlett
H. Yuan, Z. Sun
Letter
(m, 3 H), 6.80 (d, J = 7.1 Hz, 1 H), 3.81 (s, 3 H). 13C{ H} NMR (101
1
NMR (101 MHz, CDCl ):  = 164.3, 153.7, 134.0, 133.7, 133.3,
3
1
32.7, 128.6 (d, J = 3.2 Hz), 128.2, 127.8, 127.5, 126.9, 126.6,
MHz, CDCl ):  = 129.6, 129.3, 128.8, 128.5, 127.3, 112.0, 104.9,
55.2, 29.7. HRMS (ESI-TOF): m/z [M + H] calcd for C14H11NOSH:
242.0637; found: 242.0634.
3
+
126.2, 125.0 (d, J = 18.6 Hz), 120.0. HRMS (ESI-TOF): m/z [M +
+
H] calcd for C17H11NSH: 262.0685; found: 262.0683.
3
-(1-Methyl-1H-pyrrol-3-yl)-benzo[d]isothiazole (9g): eluent
3-Furan-2-yl-5-methoxy-benzo[d]isothiazole (9l): eluent
PE/EtOAc (20:1, v/v), colorless oil; yield: 122 mg (81%). H NMR
1
1
PE/EtOAc (20:1, v/v), colorless oil; yield: 127 mg (86%). H NMR
(
400 MHz, CDCl ):  = 8.31 (d, J = 8.3 Hz, 1 H), 7.98 (d, J = 8.1 Hz,
(400 MHz, CDCl ):  = 8.02 (d, J = 2.3 Hz, 1 H), 7.82 (d, J = 8.9 Hz,
3
3
1
6
H), 7.57 (t, J = 7.5 Hz, 1 H), 7.52−7.46 (m, 1 H), 6.87 (s, 1 H),
1 H), 7.67 (d, J = 1.1 Hz, 1 H), 7.24 (m, 1 H), 7.18 (m, 1 H), 6.64
.80−6.74 (m, 1 H), 6.36−6.26 (m, 1 H), 3.98 (s, 3 H). 13C{ H}
1
(m, 1 H), 3.98 (s, 3 H). C{ H} NMR (101 MHz, CDCl ):  = 158.2,
13
1
3
NMR (101 MHz, CDCl ):  = 164.1, 160.6, 153.4, 133.8, 130.0,
153.3, 150.9, 146.5, 143.1, 134.0, 120.3, 119.3, 111.8, 110.2,
105.7, 55.7. HRMS (ESI-TOF): m/z [M + Na] calcd for C12H9-
3
+
1
27.9, 127.5, 125.0, 124.9, 120.0, 114.3, 55.4. HRMS (ESI-TOF):
+
m/z [M + H] calcd for C12H10N SH: 215.0634; found: 215.0637.
NO SNa: 254.0246; found: 254.0245.
2
2
3
-Furan-2-yl-benzo[d]isothiazole (9h): eluent PE/EtOAc (20:1,
5-Methoxy-3-(4-trifluoromethyl-phenyl)-benzo[d]isothi-
1
v/v), yellow oil; yield: 118 mg (81%). H NMR (400 MHz, CDCl ):

azole (9m): eluent PE/EtOAc (20:1, v/v), yellow oil; yield: 125
3
1
= 8.68−8.61 (m, 1 H), 8.02−7.93 (m, 1 H), 7.72−7.64 (m, 1 H),
mg (78%). H NMR (400 MHz, CDCl ):  = 8.01 (d, J = 8.1 Hz, 2 H),
3
13
1
7.55 (m, 2 H), 7.22 (m, 1 H), 6.64 (m, 1 H). C{ H} NMR (101
7.90 (d, J = 8.9 Hz, 1 H), 7.84 (d, J = 8.2 Hz, 2 H), 7.50 (d, J = 2.2
13
1
MHz, CDCl ):  = 153.9, 153.2, 150.7, 143.3, 132.8, 127.7, 125.3,
Hz, 1 H), 7.28 (m, 1 H), 3.91 (s, 3H). C{ H} NMR (101 MHz,
3
+
125.2, 119.7, 111.8, 110.4. HRMS (ESI-TOF): m/z [M + H] calcd
CDCl ):  = 162.0, 158.3, 147.0, 138.8, 134.8, 128.9, 125.3 (q,
3
19
for C11H NOSH: 202.0322; found: 202.0321.
J = 3.8 Hz), 120.7, 119.3, 104.8, 55.7. F NMR (376 MHz, CDCl ):
 = −62.64 (s). HRMS (ESI-TOF): m/z [M + Na] calcd for
7
3
+
6-Methoxy-3-phenyl-benzo[d]isothiazole (9i): eluent PE/EtOAc
1
(20:1, v/v), light yellow oil; yield: 111 mg (73%). H NMR (400
C15H10F3NOSNa: 332.0327; found: 332.0325.
MHz, CDCl ):  = 7.77−7.66 (m, 2 H), 7.57−7.49 (m, 2 H), 7.46
3
©
2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E