Iron-Promoted Three-Component 2-Substituted Benzothiazole Formation via Nitroarene ortho-C-H Sulfuration with Elemental Sulfur

Article abstract of DOI:10.1021/acs.joc.8b02619

A three-component procedure for the preparation of 2-substituted benzothiazoles from nitroarenes, alcohols, and sulfur powder is described. The reaction showed a good functional group tolerance to provide the heterocyclic products in moderate to good yields. The sequential assembly involving nitro reduction, C-N condensation, and C-S bond formation has been realized in one pot.

Full text of DOI:10.1021/acs.joc.8b02619

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Article
Iron-Promoted Three-Component 2-Substituted Benzothiazole
Formation via Nitroarene ortho C-H Sulfuration with Elemental Sulfur
Qiaoyan Xing, Yanfeng Ma, Hao Xie, Fuhong Xiao, Feng Zhang, and Guo-Jun Deng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02619 • Publication Date (Web): 04 Jan 2019
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Iron-Promoted Three-Component 2-Substituted Benzothiazole For-
mation via Nitroarene ortho C-H Sulfuration with Elemental Sulfur
Qiaoyan Xing,a Yanfeng Ma,a Hao Xie,a Fuhong Xiao,a Feng Zhang*a,b , Guo-Jun Deng*a
aKey Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally
Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105,
China
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bCollege of Science, Hunan Agricultural University, Changsha, 410128, China.
H
H
FeCl3
NO2
H
S
N
OH
NH4I, KHCO3
R1
R1
+
+
S8
NMP, 160 oC
* Simplicity to complexity
Fe catalyst hydrogen-transfer
one-pot operation
reaction conditions
C-H sulfuration
multi C-X bonds
* Gram-scale, yields up to 87%
Supporting Information
ABSTRACT: A three-component procedure for the preparation of 2-substituted benzothiazoles from nitroarenes, alcohols and
sulfur powder is described. The reaction showed good functional group tolerance to provide the heterocyclic products in moderate
to good yields. The sequential assembly involving nitro reduction, C–N condensation and C–S bond formation has been realized in
one
pot.
■ INTRODUCTION
Classic method (from aniline der ivatives)
oxidative
condensation
NH2
N
S
CHO
Carbon-heteroatom bonds such as C–N, C–O and C–S are
basic fragments of heterocycles as well as various functional
molecules. Therefore, the construction of carbon-heteroatom
bonds attracts considerable interest in organic chemistry.1 The
classic cross-coupling reaction between functionalized sub-
strates probably is the most powerful protocol for constructing
carbon-heteroatom bonds.2 However, the use of functionalized
substrates in such transformation often leads to the production
of a large amount of wastes, thus reducing the atom economy
of the reaction. The recent use of transition-metal-catalyzed
C–H functionalization methods for the formation of carbon-
heteroatom bonds represents an exciting alternative.3 This kind
of reaction eliminates pre-functionalization of the substrates
(one or both) and thus provides a more direct approach.
Among them, the arene C–H bond sulfuration has proved to be
very powerful to construct C–S bond.4 Thiols,5 disulfides,6
sodium sulfinates,7 sulfonyl chlorides8 and sulfonyl hydra-
zides9 are frequently used as the coupling partners even in the
absence of transition-metal catalysts.10 When thiobenzanilides
were used as the substrates, 2-substituted benzothiazoles could
be achieved via intramolecular C–H thiolation.11 In recent
R1
R1
C
(a)
(b)
+
X
X = SH, halogen, H
From or tho-functionalized nitr oar enes
NO2
S
NH2
pyridine
R1
R1
+
S8
+
N
Halogen
This strategy (fr om simple nitroarenes)
H
H
NO2
S
N
OH
Fe/NH4I
base, solvent
R1
(c)
R1
+
S8
+
H
Hyd rogen-transfer strategy!
Nitroarene C-H sulfur ation!
S8 as sulfenylating r eagent!
Scheme 1. Three-Component 2-Substituted Benzothiazole
Formation via C-H Sulfuration of Nitroarene C-H Bond
with Elemental Sulfur
years, stable and readily available elemental sulfur has been
successfully applied for the direct sulfuration of arenes esp
cially for electron-rich heterocycles such as indoles and ani-
lines (Willgerodt Reaction).12 However, direct sulfuration of
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electron-deficient C–H bonds with elemental sulfur is more
challenging since its relatively low reactivity.
a
Table 1. Optimization of Reaction Conditions
Nitroarenes are readily available chemicals via nitration of
arenes and frequently used as building blocks for the synthesis
of pharmaceuticals, agrochemicals and fine chemicals.13 These
compounds can be converted into various functionalized ni-
troarenes via halogenation, hydroxylation, nitration and ami-
nation processes.14 Although some recent research revealed
that selective ortho arylation and benzylation could be
achieved in the aid of Pd catalysts,15 regioselectivity control is
always problematic and functionalized nitroarene is a minor
product in most cases. Recently, Nguyen and co-workers
succesfully converted ortho-functionalized nitroarenes into
various heterocycles (Scheme 1, b).16 Without doubt, regiose-
lective functionalization of simple and readily available ni-
troarenes can provide a simple and direct synthetic protocol
for the construction of various nitrogen-containing functional
materials. In the past several years, we17 and others developed
various procedures for C–N bond formation using simple
nitroarenes as the substrates.18 When alcohols or cyclohexa-
nones were used as the coupling partners, they also could act
as the hydrogen donor to reduce the nitro group via the hydro-
gen-transfer or borrowing hydrogen process.19 These methods
could provide alternative approaches for the construction of
various amines or nitrogen-containing heterocycles directly
from nitroarenes. As our continuing interest in the preparation
of heterocycles via direct C–H sulfuration using sulfur powder
as the sulfur source,12d-i we herein report an iron-promoted
three-component synthesis of 2-aryl-benzothiazoles,20 using
readily available nitroarenes, alcohols and sulfur powder as
the raw materials (Scheme 1, c).
4
5
6
7
8
9
Yield[
Entry
Catalyst
Additive
Base
Solvent
b]
1
2
-
Fe
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
-
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
-
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
NMP
DMSO
CH3NO2
DMF
NMP
NMP
NMP
38
38
45
85
46
42
32
57
40
14
69
74
63
63
76
79
40
72
65
79
10
0
10
11
12
13
14
15
16
17
18
19
20
21
22
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60
3
DPPF
FeCl3
4
5
FeSO4·7H2O
Fe2SO3
Fe(acac)3
FeCl2
6
7
8
9
Ferrocene
FeCl3
10
11
12
13
14
15
16
17
18
19[c]
20[d]
21
22
23
24[e]
25[f]
FeCl3
KI
FeCl3
TMAI
I2
FeCl3
FeCl3
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
FeCl3
K2CO3
KOH
FeCl3
FeCl3
K3PO4
tBuOH
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
FeCl3
■ RESULTS AND DISCUSSION
FeCl3
FeCl3
To obtain optimization conditions for the three-component
reaction, 1-methyl-4-nitrobenzene (1a), phenylmethanol (2a),
and sulfur powder were initially used as the standard sub-
strates (Table 1). When the reaction was performed using
NH4I as the additive and KHCO3 as the base, the desired prod-
uct 3aa was obtained in 38% yield (entry 1). To further pro-
mote the reaction yield, various non-toxic iron catalysts were
screened based on our previous research. No change was ob-
served when iron powder was used (entry 2). The addition of
10 mol% of DPPF slightly improved the reaction yield to 45%
(entry 3). To our delight, the desired product 3aa was obtained
in 85% yield when catalytic amounts of FeCl3 were added
(entry 4). Other iron catalysts such as FeSO4, Fe2SO3,
Fe(acac)3, FeCl2 and Ferrocene are less effective under similar
conditions (entries 5-9). Additive NH4I plays an important role
in this kind of transformation, only 14% was obtained when
the reaction was carried out in the absence of it (entry 10).
Other iodide-containing additives were also investigated and
the use of KI, TMAI and iodine were also proved to be effec-
tive (entries 11-13). The reaction yield decreased to 63% in
the absence of base (entry 14). Other inorganic bases such as
FeCl3
FeCl3
FeCl3
16
62
68
85
FeCl3
FeCl3
26[g]
FeCl3
a
Reaction conditions: 1a (0.25 mmol), 2a (0.2 mmol), S8 (32
mg, 0.125 mmol), catalyst (10 mol %), additive (1equiv),
base (50 mol %) and solvent (0.4 mL) under argon at 160 oC
b
c
d
for 24 h. GC yield based on 2a. Under air. S8 (19.2 mg,
0.075 mmol). eAt 150oC. f-gFor 20 and 28 h.
shortened to 20 h and the yield of 3aa was 68% (entry 25). No
further improvement in yield was obtained in 28 h (entry 26).
With the optimized reaction conditions established, we next
studied the substrate scope by testing different alcohols with
1-methyl-4-nitrobenzene (1a) and elemental sulfur, and the
results were summarized in Table 2. First, benzylic alcohols
with various substituents at the para position were investigated.
The introduction of methyl and isopropyl groups slightly af-
fected the reaction yields (3ab and 3ac). Lower yield was
obtained when (4-methoxyphenyl)methanol (2d) was used as
substrate, with a considerable generation of 4-methoxy-N-(p-
tolyl)benzamide. When (4-(methylthio)phenyl)methanol (2e)
t
K2CO3, KOH and BuOK also showed good efficiency to
provide the product 3aa in good yield (entries 15, 16 and 18).
The reaction atmosphere is important to the reaction and lower
yield was observed when the reaction was carried out under air
(entry 19). Good yield was still achieved when 3 equiv of
sulfur powder were used (entry 20).Other solvents are not
suitable for this reaction (entries 21-23). The yield of 3aa
o
decreased sharply at 150 C (entry 24). the reaction time was
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FeCl3
was used as the reactant, the corresponding product 3ae was
obtained in 62% yield. Halogen substituents such as fluoro,
2
3
NO2
N
NH4I, KHCO3
+
+
S8
Ar
Ar
Ph
Ph
Ph
OH
2a
NMP, 160 o
C
S
chloro and trifluoromethyl were well tolerated to give the
products in good to high yields (3af, 3ag and 3ai). However,
much lower yield was obtained when a bromo substituent
presented (3ah). We were quite pleased to observe no steric
effect in this kind of transformation. For example, good yields
were obtained when a methyl or chloro group existed at the
ortho position, which delivered 3aj and 3ak in 73% and 80%
yield, respectively. Moderate to good yields were obtained
when two halogen substituted benzyl alcohols were used as
the reactants (3ao). Although simple aliphatic alcohols were
not effective reactants under the current reaction conditions,
3aq could be obtained in 35% yield when 2-phenylethan-1-ol
was used. To our delight, (pyridin-2-yl)methanol also could be
used as the coupling partner to give the desired product 3ap in
40% yield. Unfortunately, relatively less reactive aliphatic
alcohols were not suitable substrates for this transformation.
4
5
6
7
8
9
1
3
O
R = H, 3ba, 52%
3ca
R = 3-CH3,
, 75%
R = 4-Et, 3da, 80%
3ea
N
N
N
S
R
Ph
S
R = 4-OCH3,
, 52%
3fa
, 35%
R = 4-F,
3ga
3ia'
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12
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19
20
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22
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, 65%
H
N
F
N
N
S
N
S
Ph
N
Ph
Ph
S
NH
N
3ia
3ha
, 80%
79% (3ia/3ia' = 10/1)
H
N
N
N
S
N
S
Ph
N
Ph
Ph
Ph
S
NH
Table 2. Substrate Scope with Respect to Alcoholsa
N
3ja
, 25%
3ka
3ka'
80% (3ka/3ka' = 95/5)
N
S
N
S
S
N
N
Ph
Ph
H2N
N
N
S
S
3la
3ma
3ma'
, 53%
3ma 3ma'
35% (
/
= 20/1)
N
S
N
N
S
Ph
N
S
H2N
Ph
Ph
S
N
S
HN
3oa
3oa'
N
H2N
3oa 3oa'
3na
, 79%
75% (
/
= 5/1)
3oa 3oa'
= 11/1)
b
87% , 1.23 g, (
/
presented at the ortho position of the fluoro group (3ha). Mor-
pholine functional group was well tolerated under the given
conditions to give the corresponding product 3ga in 65% yield.
Significant steric effect was observed in the nitroarene sub-
strate and only 25% yield was obtained when 1-
nitronaphthalene was used as the substrate (3ja). To our de-
light, 5-nitropyridin-2-amine could smoothly react with benzyl
alcohol and elemental sulfur to give the product 3la in moder-
ate yield. In this reaction, free amino group was tolerated and
the cyclization reaction selectively occurred at the ortho posi-
tion of the nitrogen atom. Several nitrohetarenes were also
tested when 5-nitro-1H-indazole was used as the substrate,
product 3na was formed in 79% isolated yield with high levels
a Reaction conditions: 1a (0.25mmol), 2 (0.2 mmol), S8 (32 mg,
0.125 mmol), FeCl3 (10 mol %), KHCO3 (50 mol %), NH4I (1
o
equiv), NMP (0.4mL), under argon, 160 C, 24 h. Isolated
yield based on 2. b For 32 h.
′
of regioselectivity. Two products 3ia and 3ia (10:1) were
obtained in a combination yield of 79% when 6-nitro-1H-
indazole was used as the substrate. The ratio of 3ka:3ka
Furthermore, we examined the reactions between various
nitroarenes, benzyl alcohol (2a) and elemental sulfur (Table 3).
The reaction between simple nitrobenzene and benzyl alcohol
provided the corresponding product 3ba in moderate yield.
Better yields were observed when methyl and ethyl substitu-
ents located at the para position of the nitro group (3ca and
3da). The presence of methoxy group did not affect the reac-
tion yield (3ea). Low yield was obtained when 4-
fluoronitrobenzene was used as the reactant (3fa). Delightedly,
much higher yield could be achieved when a methyl group
′
could be improved when a methyl substituent presented at the
heterocycle ring. The product was obtained in 35% yield when
5-nitrobenzo[d]thiazole was used as the reactant (3ma/3ma' =
20/1). Better yield could be achieved when a free amino group
was presented at the heterocycle ring, in which the cyclization
reaction mainly occurred at the C4-position of the benzene
ring (3oa/3oa' = 5/1). Both the reaction yield and the regiose-
lectivity of 3oa/3oa' was improved when the reaction was
carried out on a gram scale.
Some control experiments were carried out to gain more in-
formation
methylbenzylidene)aniline (4aa) was obtained as the major
product when the reaction was carried out in the absence of
sulfur powder (Scheme 2, a). This result indicates that alco-
Table 3. Substrate Scope with Respect to Nitrobenzenesa
a Reaction conditions: 1 (0.25mmol), 2a (0.2 mmol), S8 (32 mg,
0.125 mmol), FeCl3 (10 mol %), KHCO3 (50 mol %), NH4I (1
about
the
mechanism.
N-(4-
o
equiv), NMP (0.4 mL), under argon, 160 C, 24 h. Isolated
yield based on 2a. b5 mmol scale.
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hols could act as the hydrogen donor to reduce the nitro group
via a hydrogen-transfer process. Nitroarene 1a is reduced to
amine by the hydrogen generated during the alcohol oxidation
step via a hydrogen-transfer process in the presence of iron
catalyst, and benzyl alcohol 2a is oxidized into the corre-
sponding aldehyde. Subsequent condensation of amine with
aldehyde affords an imine intermediate 4aa.17 When the reac-
tion was performed within 5 h under standard conditions, the
3
4
5
6
7
8
9
6-methyl-2-phenylbenzothiazole
methylbenzylidene)aniline
(3aa),
and
N-(4-
N-(p-
(4aa)
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11
12
13
14
15
16
17
18
19
20
21
22
23
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tolyl)benzothioamide (4aa') were produced in 40%, 10% and
25% GC yields, respectively (Scheme 2, b). We speculate that
imine intermediate 4aa could be oxidized by elemental sulfur
to form thioamides 4aa'.21 This means that sulfur powder also
could act as the reducing agent to reduce the nitro group.
Treatment of N-(p-tolyl)benzothioamide (4aa') with sulfur
powder
without
NH4I
gave
the
6-methyl-2-
phenylbenzothiazole (3aa) in 38% GC yield (Scheme 2, c).
However, no reaction occurred upon the treatment of 4aa'
with sulfur powder in the absence of FeCl3 (Scheme 2, d).
These observations imply that the oxidative annulations of
4aa' was directly enabled by the FeCl3 catalyst to afford the
desired product 3aa. No desired product was obtained when
4aa was treated with sulfur powder without NH4I (Scheme 2,
e), but the desired product 3aa can be obtained in the absence
of FeCl3 (Scheme 2, f). These results mean oxidative annula-
tions of 4aa was mainly catalyzed by NH4I.22 These results
also verified that the desired product 3aa could be obtained
when the reaction was carried out without NH4I or FeCl3 (Ta-
ble 1, entries 1 and 8), thus indicated that this reaction proba-
bly involves two different pathways.
Scheme 2. Control Experiments
Based on the aforementioned experimental results, we pro-
posed a possible reaction mechanism (Scheme 3). Initially, N-
(4-methylbenzylidene)aniline
4aa
and
N-(p-
tolyl)benzothioamide (4aa') are generated from 1a and 2a.
Then nucleophilic attacks of sulfur powder to 4aa affords
intermediate A, which proceeds through elimination of Sn-1 and
cyclization to give intermediate B. The final desired product
3aa is formed through deprotonation and oxidation of B.12e
Meanwhile, the 4aa' was oxidized by Fe(III) to form the thioyl
radical intermediate C. The cyclization of the thioyl radical
intermediate C followed by oxidation process in the presence
of sulfur powder gave the product 3aa.23
Scheme 3. Proposed mechanism.
In summary, we have developed a versatile method for the
synthesis of 2-arylbenzothiazole from nitroarenes, alcohols
and elemental sulfur. The combination use of FeCl3 and NH4I
could significantly improve the reaction yield. The ortho posi-
tion of the nitro group was directly functionalized to selective-
ly provide a new C–S bond formation with elemental sulfur.
The nitro reduction, C–N condensation and C–S bond for-
mation were realized in one pot. This method affords an alter-
native approach for the synthesis of biologically important 2-
substituted benzothiazoles from readily available starting
materials.
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1H), 2.97 (d, J = 13.3, 6.7 Hz, 1H), 2.49 (s, 3H), 1.29 (d, J =
6.9 Hz, 6H). 13C{1H} NMR (100 MHz, CDCl3) δ 167.3 (C-2),
152.2, 151.9, 135.3, 134.9, 131.1, 127.9, 127.5, 127.1, 122.4,
121.3, 34.1, 23.8 (CH(CH3)2), 21.5 (CH3). HRMS (ESI) m/z
calcd for C17H18NS+ (M+H)+ 268.1155, found 268.1150.
2-(4-Methoxyphenyl)-6-methylbenzothiazole (Table 2, 3ad)26:
■ EXPERIMENTAL SECTION
8
9
eluent, petroleum ether/ethyl acetate = 20:1, (white solid 29.6
1
mg, 58% yield, mp = 176-177 °C), H NMR (400 MHz,
General Methods. All reactions were carried out under Ar
atmosphere unless otherwise noted. Column chromatography
was performed using aluminum oxide (neutral) (100-200
mesh). 1H NMR and 13C NMR spectra were recorded on
Bruker-AV (400 and 100 MHz, respectively) instrument inter-
nally referenced to tetramethylsilane (TMS), chloroform or
DMSO signals. Mass spectra were measured on Agilent 5975
GC-MS instrument (EI). HRMS was conducted using elec-
trospraying ionization (ESI) and was performed on a Thermo
Scientific LTQ Orbitrap XL at Keecloud (Shanghai) Biotech-
nology Co. LTD. The structures of known compounds were
CDCl3) δ 8.03 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.3 Hz, 1H),
7.66 (s, 1H), 7.29 (d, J = 8.3 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H),
3.88 (s, 3H), 2.49 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ
167.0 (C-2), 161.9 (C6H4OMe), 151.8, 135.1, 134.7, 129.1,
127.9, 126.2, 122.2, 121.3, 114.4, 55.5 (OCH3), 21.5 (CH3).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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6-Methyl-2-(4-methylsulfanyl-phenyl)-benzothiazole (Table 2,
3ae)27: eluent, petroleum ether/ethyl acetate = 20:1, (white
1
solid 33.6 mg, 62% yield, mp = 184-185 °C), H NMR (400
MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 8.3 Hz,
1H), 7.67 (s, 1H), 7.30 (t, J = 7.9 Hz, 3H), 2.54 (s, 3H), 2.49 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 166.6 (C-2), 151.9
(C6H4SMe), 142.6, 135.3, 134.8, 130.0, 128.0, 127.7, 126.0,
122.4, 121.3, 21.5 (CH3), 15.2 (SCH3).
further corroborated by comparing their H NMR, 13C NMR
1
data and MS data with those of literature. All reagents were
obtained from commercial suppliers and used without further
purification. The molecular weight of S8 is determined to be
32 g/mol unless otherwise noted.
6-Methyl-2-(4'-fluorophenyl)-1,3-benzothiazole (Table 2,
3af)28: eluent, petroleum ether/ethyl acetate = 50:1, (white
solid (31.6 mg, 65% yield), mp = 149-150 °C), 1H NMR (400
MHz, CDCl3) δ 8.07 – 8.00 (m, 2H), 7.92 (d, J = 8.3 Hz, 1H),
7.65 (s, 1H), 7.28 (dd, J = 8.3, 1.1 Hz, 1H), 7.19 – 7.12 (m,
2H), 2.48 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 165.6
(C-2), 164.3 (C6H4F) (d, J = 251.5 Hz), 152.2, 135.4, 135.2,
130.0 (d, J = 3.2 Hz), 129.3 (d, J = 8.6 Hz), 128.0, 122.6,
121.3, 116.0 (d, J = 22.1 Hz), 21.5 (CH3).
General procedure (3aa) A 10 mL oven-dried reaction
vessel was charged with KHCO3 (10 mg, 0.1 mmol), NH4I (29
mg, 0.2 mmol), FeCl3 (4 mg, 0.02mmol), 1-methyl-4-
nitrobenzene (1a, 34.3 mg, 0.25 mmol), phenylmethanol (2a,
21 μL, 0.2mmol), sulfur powder (32 mg, 0.125 mmol) and
NMP (0.4 mL) under argon. The sealed reaction vessel was
o
stirred at 160 C for 24 h. After cooling to room temperature,
the reaction was diluted with ethyl acetate (5 mL) and washed
with saturated sodium chloride solution. The organic layer was
separated, and the aqueous layer was extracted with ethyl
acetate for three times. The combined organic layer was dried
over magnesium sulfate and the volatiles were removed under
reduced pressure. The residue was purified by column chro-
matography on silica gel (petroleum ether/ethyl acetate = 50:1)
to yield the desired product 3aa as white solid (33.8 mg, 75%
yield), mp = 124-125 oC.24 1H NMR (400 MHz, CDCl3) δ 8.07
(d, J = 4.1 Hz, 2H), 7.95 (d, J = 8.3 Hz, 1H), 7.69 (s, 1H), 7.48
(s, 3H), 7.30 (d, J = 8.2 Hz, 1H), 2.50 (s, 3H). 13C{1H} NMR
(100 MHz, CDCl3) δ 167.0 (C-2), 152.2, 135.4, 135.2, 133.7,
130.8, 129.0, 127.9, 127.4, 122.7, 121.4, 21.5 (CH3).
2-(4-Chlorophenyl)-6-methylbenzothiazole (Table 2, 3ag)29:
eluent, petroleum ether/ethyl acetate = 50:1, (white solid 41.5
1
mg, 80% yield, mp = 192-193 °C), H NMR (400 MHz,
CDCl3) δ 8.02 (d, J = 8.0 Hz, 2H), 7.95 (d, J = 8.2 Hz, 1H),
7.70 (s, 1H), 7.46 (d, J = 7.8 Hz, 2H), 7.32 (d, J = 8.4 Hz, 1H),
2.50 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 165.6 (C-2),
152.1, 136.8 (C6H4Cl), 135.7, 135.2, 132.2, 129.2, 128.6,
128.2, 122.7, 121.4, 21.6 (CH3).
2-(4-Bromophenyl)-6-methylbenzo[d]thiazole
(Table
2,
3ah)26: eluent, petroleum ether/ethyl acetate = 50:1, (white
1
solid 25.5 mg, 42% yield, mp = 175-176 °C), H NMR (400
MHz, CDCl3) δ 7.93 (dd, J = 8.3, 6.3 Hz, 3H), 7.67 (s, 1H),
7.60 (d, J = 8.5 Hz, 2H), 7.30 (d, J = 8.4 Hz, 1H), 2.49 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 165.7 (C-2), 152.0, 135.7
(C6H4Br), 135.1, 132.5, 132.2, 128.8, 128.1, 125.2, 122.7,
121.4, 21.6 (CH3).
The unknown compounds were characterized properly by
their spectroscopic and spectrometric data (1H NMR, 13C{1H}
NMR, and ESI).
2-(4-Chlorophenyl)-6-methyl-1,3-benzothiazole (Table 2,
3ab)25: eluent, petroleum ether/ethyl acetate = 50:1,(white
6-Methyl-2-[4-(trifluoromethyl)phenyl]-1,3-benzothiazole
(Table 2, 3ai): eluent, petroleum ether/ethyl acetate = 50:1,
(white solid 42.8 mg, 73% yield, mp = 189-190 °C), 1H NMR
(400 MHz, CDCl3) δ 8.19 (d, J = 7.8 Hz, 2H), 7.99 (d, J = 8.5
Hz, 1H), 7.78 – 7.69 (m, 3H), 7.34 (d, J = 8.3 Hz, 1H), 2.52 (s,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 165.0 (C-2), 152.0,
136.8, 136.1, 135.3, 132.3 (C6H4CF3) (q, J = 33.0 Hz), 128.3,
127.6, 126.0 (q, J = 3.8 Hz), 123.8 (CF3) (q, J = 270.7 Hz),
123.0, 121.5, 21.6 (CH3). HRMS (ESI) m/z calcd for
C15H11F3NS+ (M+H)+ 294.0559, found 294.0562.
solid 33.5 mg, 70% yield, mp = 150-151 C), 1H NMR (400
o
MHz, CDCl3) δ 7.96 (t, J = 8.8 Hz, 3H), 7.68 (s, 1H), 7.29 (d,
J = 7.7 Hz, 3H), 2.49 (s, 3H), 2.42 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 167.3 (C-2), 152.0, 141.3, 135.2, 134.9
(C6H4Br), 130.7, 129.7, 127.9, 127.4, 122.4, 121.3, 21.5 (CH3),
21.5 (CH3).
6-Methyl-2-(4-propan-2-ylphenyl)-1,3-benzothiazole (Table
2, 3ac): eluent, petroleum ether/ethyl acetate = 50:1, (white
solid 38.5 mg, 72% yield, mp = 105-106 °C), H NMR (400
MHz, CDCl3) δ 8.01 (d, J = 8.2 Hz, 2H), 7.96 (d, J = 8.3 Hz,
1H), 7.68 (s, 1H), 7.34 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 7.7 Hz,
1
6-Methyl-2-(2-methylphenyl)-1,3-benzothiazole (Table 2,
3aj)30: eluent, petroleum ether/ethyl acetate = 50:1, (yellow oil
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34.9 mg, 73% yield), 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J
6-Methyl-2-pyridin-2-yl-benzothiazole (Table 2, 3ap)32:
= 8.3 Hz, 1H), 7.64 (d, J = 7.3 Hz, 1H), 7.59 (s, 1H), 7.27 –
7.17 (m, 4H), 2.55 (s, 3H), 2.40 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 167.0 (C-2), 152.0, 137.2, 135.8 (C6H4Me),
135.3, 133.2, 131.5, 130.5, 129.9, 127.8, 126.1, 122.9, 121.1,
21.6 (CH3), 21.4 (CH3).
eluent, petroleum ether/ethyl acetate = 50:1, (white solid 18.1
1
mg, 40% yield, mp = 165–166 °C), H NMR (400 MHz,
CDCl3) δ 8.69 (s, 1H), 8.38 (d, J = 7.8 Hz, 1H), 7.98 (d, J =
8.4 Hz, 1H), 7.85 (dd, J = 11.0, 4.4 Hz, 1H), 7.76 (s, 1H), 7.41
– 7.36 (m, 1H), 7.33 (d, J = 8.5 Hz, 1H), 2.51 (s, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 168.3 (C-2), 152.3 (C6H4N), 151.4,
149.6, 137.0, 136.0, 136.2, 128.0, 125.1, 123.0, 121.7, 120.7,
21.6 (CH3).
2-(2-Chlorophenyl)-6-methylbenzo[d]thiazole (Table 2,
3ak)31: eluent, petroleum ether/ethyl acetate = 50:1, (white
9
1
solid 41.5 mg, 80% yield, mp = 100–101 °C), H NMR (400
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12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
MHz, CDCl3) δ 8.20 (d, J = 3.7 Hz, 1H), 8.01 (d, J = 8.3 Hz,
1H), 7.74 (s, 1H), 7.57 – 7.50 (m, 1H), 7.43 – 7.37 (m, 2H),
7.34 (d, J = 8.3 Hz, 1H), 2.52 (s, 3H). 13C{1H} NMR (100
MHz, CDCl3) δ 163.1 (C-2), 150.6, 136.3, 135.7, 132.6, 132.3
(C6H4Cl), 131.7, 131.0, 130.8, 128.0, 127.1, 122.9, 121.0, 21.6
(CH3).
2-Benzyl-6-methylbenzo[d]thiazole (Table 2, 3aq)33: eluent,
petroleum ether/ethyl acetate = 20:1, (yellow oil 16.8 mg, 35%
yield), 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.3 Hz, 1H),
7.56 (s, 1H), 7.39 – 7.31 (m, 4H), 7.30 – 7.23 (m, 2H), 4.41 (s,
2H), 2.45 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 170.0
(C-2), 151.3, 137.3, 135.8, 134.9, 129.2, 128.89, 127.59, 127.3,
122.2, 121.2, 40.5, 21.4.
6-Methyl-2-(3-phenoxyphenyl)benzo[d]thiazole (Table 2,
3al): eluent, petroleum ether/ethyl acetate = 50:1, (white solid
2-Phenylbenzothiazole (Table 3, 3ba)34: eluent, petroleum
ether/ethyl acetate = 50:1, (white solid 22.0 mg, 52% yield,
mp = 108–111 °C), 1H NMR (400 MHz, CDCl3) δ 8.13 – 8.05
(m, 3H), 7.91 (d, J = 8.0 Hz, 1H), 7.53 – 7.46 (m, 4H), 7.42 –
7.35 (m, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 168.1 (C-2),
154.0, 135.0, 133.5, 131.0, 129.0, 127.6, 126.4, 125.2, 123.2,
121.6.
1
43.8 mg, 69% yield, mp = 100–101 °C), H NMR (400 MHz,
CDCl3) δ 7.93 (d, J = 8.2 Hz, 1H), 7.80 (d, J = 7.7 Hz, 1H),
7.75 (s, 1H), 7.67 (s, 1H), 7.43 (t, J = 7.9 Hz, 1H), 7.37 (t, J =
7.1 Hz, 2H), 7.29 (d, J = 8.3 Hz, 1H), 7.18 – 7.04 (m, 4H),
2.49 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 166.2 (C-2),
157.8 (C6H4O), 156.8 (C6H5O), 152.1, 135.6, 135.4, 135.2,
130.3, 129.9, 128.0, 123.6, 122.8, 122.3, 121.3, 121.0, 119.0,
117.6, 21.6 (CH3). HRMS (ESI) m/z calcd for C20H16NOS+
(M+H)+ 318.0947, found 318.0948.
5-Methyl-2-phenylbenzo[d]thiazole (Table 3, 3ca)35: eluent,
petroleum ether/ethyl acetate = 50:1, (white solid 33.8 mg, 75%
yield, mp = 145–146 °C), 1H NMR (400 MHz, CDCl3) δ 8.09
(dd, J = 6.6, 2.9 Hz, 2H), 7.89 (s, 1H), 7.77 (d, J = 8.2 Hz, 1H),
7.51 – 7.47 (m, 3H), 7.22 (d, J = 8.0 Hz, 1H), 2.52 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 168.2 (C-2), 154.3, 136.5,
133.6, 131.9, 130.9, 129.0, 127.5, 126.9, 123.2, 121.1, 21.5
(CH3).
2-(3-Fluorophenyl)-6-methyl-1,3-benzothiazole (Table 2,
3am): eluent, petroleum ether/ethyl acetate = 50:1, (white
1
solid 37.5 mg, 77% yield, mp = 110–111 °C), H NMR (400
MHz, CDCl3) δ 7.94 (d, J = 8.3 Hz, 1H), 7.82 – 7.77 (m, 2H),
7.66 (s, 1H), 7.42 (d, J = 8.1, 5.7 Hz, 1H), 7.30 (dd, J = 8.3,
1.3 Hz, 1H), 7.15 (dd, J = 8.3, 2.5 Hz, 1H), 2.48 (s, 3H).
13C{1H} NMR (100 MHz, CDCl3) δ 165.3 (C-2) (d, J = 3.1
Hz), 163.0 (C6H4F)(d, J = 247.1 Hz), 152.0, 135.7 (d, J = 5.7
Hz), 135.2, 130.5 (d, J = 8.2 Hz), 128.1, 127.6, 123.1 (d, J =
3.0 Hz), 122.9, 121.3, 117.6 (d, J = 21.4 Hz), 114.1 (d, J =
23.5 Hz), 21.5 (CH3). HRMS (ESI) m/z calcd for C14H11FNS+
(M+H)+ 244.0591, found 244.0592.
6-Ethyl-2-phenylbenzo[d]thiazole (Table 3, 3da)12e: eluent,
petroleum ether/ethyl acetate = 50:1, (white solid 38.3 mg, 80%
yield, mp = 60–61 °C), 1H NMR (400 MHz, CDCl3) δ 7.94 (dd,
J = 6.4, 2.9 Hz, 2H), 7.86 (d, J = 8.4 Hz, 1H), 7.54 (s, 1H),
7.33 (dd, J = 4.9, 1.6 Hz, 3H), 7.19 (dd, J = 8.4, 1.2 Hz, 1H),
2.64 (q, J = 7.6 Hz, 2H), 1.17 (t, J = 7.6 Hz, 3H). 13C{1H}
NMR (100 MHz, CDCl3) δ 167.0 (C-2), 152.3, 141.7, 135.2,
133.7, 130.6, 128.9, 127.3, 126.8, 122.7, 120.1, 28.9, 15.7
(CH2CH3).
2-(3-Bromophenyl)-6-methyl-1,3-benzothiazole (Table 2,
3an): eluent, petroleum ether/ethyl acetate = 50:1, (white solid
1
44.3 mg, 77% yield, mp = 110-111 °C), H NMR (400 MHz,
6-Methoxy-2-phenylbenzo[d]thiazole (Table 3, 3ea)12e: eluent,
petroleum ether/ethyl acetate = 20:1, (white solid 25.1 mg, 52%
yield, mp = 115 - 116 °C), 1H NMR (400 MHz, CDCl3) δ 8.07
– 8.00 (m, 2H), 7.95 (d, J = 8.9 Hz, 1H), 7.46 (dd, J = 5.2, 1.8
Hz, 3H), 7.33 (d, J = 2.5 Hz, 1H), 7.08 (dd, J = 8.9, 2.5 Hz,
1H), 3.87 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) δ 165.5
(C-2), 157.7, 148.6 (C6H3OMe), 136.3, 133.7, 130.5, 128.9,
127.2, 123.7, 115.6, 104.1, 55.7 (OMe).
CDCl3) δ 8.26 (s, 1H), 7.98 (t, J = 7.1 Hz, 2H), 7.71 (s, 1H),
7.60 (d, J = 8.0 Hz, 1H), 7.35 (dd, J = 16.7, 8.2 Hz, 2H), 2.51
(s, 3H). 13C{1H}NMR (100 MHz, CDCl3) δ 165.1 (C-2), 151.9,
135.9, 135.5, 135.1, 133.6, 130.5, 130.1, 128.2, 126.1, 123.2
(C6H4Br), 122.9, 121.4, 21.6 (CH3).
2-(2-Chloro-4-fluorophenyl)-6-methylbenzo[d]thiazole (Ta-
ble 2, 3ao): eluent, petroleum ether/ethyl acetate = 50:1,
(white solid 37.1 mg, 67% yield, mp = 148-149 °C), 1H NMR
(400 MHz, CDCl3) δ 8.17 (dd, J = 8.8, 6.2 Hz, 1H), 7.93 (d, J
= 8.4 Hz, 1H), 7.65 (s, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.20 (dd,
J = 8.3, 2.5 Hz, 1H), 2.45 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) 13C{1H} NMR (100 MHz, CDCl3) δ 163.2 (C6H3F)(d,
J = 230.1 Hz), 161.8 (C-2), 150.4, 136.1, 135.8, 133.6 (C6H3Cl)
(d, J = 10.5 Hz), 133.2 (d, J = 9.1 Hz), 128.8 (d, J = 3.7 Hz),
128.1, 122.8, 121.0, 118.0 (d, J = 25.0 Hz), 114.7 (d, J = 21.4
Hz), 21.6 (CH3). HRMS (ESI) m/z calcd for C14H10ClFNS+
(M+H)+ 278.0201, found 278.0202.
6-Fluoro-2-phenylbenzo[d]thiazole (Table 3, 3fa)36: eluent,
petroleum ether/ethyl acetate = 50:1, (white solid 16.1 mg, 35%
yield, mp = 135–136 °C), 1H NMR (400 MHz, CDCl3) δ 8.04
(dd, J = 13.8, 7.7, 3.8 Hz, 3H), 7.59 (dd, J = 8.1, 2.5 Hz, 1H),
7.53 – 7.48 (m, 3H), 7.23 (d, J = 8.9, 4.5 Hz, 1H). 13C{1H}
NMR (100 MHz, CDCl3) δ 167.8 (C-2), 160.5 (C6H3F)(d, J =
245.8 Hz), 150.7, 136.0 (d, J = 11.3 Hz), 133.4, 131.1, 129.1,
127.5, 124.1 (d, J = 9.3 Hz), 115.0 (d, J = 24.7 Hz), 107.8 (d, J
= 26.7 Hz).
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4-(2-Phenylbenzo[d]thiazol-6-yl)morpholine (Table 3, 3ga):
2-Phenylbenzo[1,2-d:4,5-d']bis(thiazole) (Table 3, 3ma) and
2-Phenylbenzo[1,2-d:4,3-d']bis(thiazole) (Table 3, 3ma’):
eluent, petroleum ether/ethyl acetate = 20:1, (white solid mix-
ture. 18.8 mg, 35% yield, 3ma/3ma’ = 20:1, mp = 159–
160 °C), 1H NMR (400 MHz, CDCl3) δ 9.03 (s, 1H), 8.21 (q, J
= 8.8 Hz, 2H), 8.15 – 8.07 (m, 2H), 8.05 (dd, J = 6.5, 3.2 Hz,
1H), 7.92 (dd, J = 16.3, 8.8 Hz, 1H), 7.55 – 7.50 (m, 3H), 7.33
(s, 1H). 13C{1H} NMR (100 MHz, CDCl3) δ 167.7 (C-2),
152.8 (C3NS), 152.4, 151.6, 133.1, 131.2, 129.2, 127.8, 127.6,
eluent, petroleum ether/ethyl acetate = 20:1, (white solid 38.5
1
mg, 65% yield, mp = 207–208 °C), H NMR (400 MHz,
CDCl3) δ 8.04 (dd, J = 7.4, 2.1 Hz, 2H), 7.95 (d, J = 9.0 Hz,
1H), 7.52 – 7.44 (m, 3H), 7.35 (s, 1H), 7.15 (dd, J = 8.9, 2.1
Hz, 1H), 3.96 – 3.86 (m, 4H), 3.29 – 3.21 (m, 4H). 13C{1H}
NMR (100 MHz, CDCl3) δ 165.3 (C-2), 149.4, 148.4 (C6H3N),
136.8, 133.9, 130.5, 129.0, 127.2, 123.4, 116.8, 106.9, 66.9
(CH2N), 50.0 (CH2O). HRMS (ESI) m/z calcd for
C17H17N2OS+ (M+H)+ 297.1056, found 297.1053.
+
126.7, 122.0, 121.6. HRMS (ESI) m/z calcd for C14H9N2S2
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(M+H)+ 269.0201, found 269.0201.
5-Fluoro-6-methyl-2-phenylbenzo[d]thiazole (Table 3, 3ha):
eluent, petroleum ether/ethyl acetate = 50:1, (white solid 38.9
mg, 80% yield, mp = 192–193 °C), H NMR (400 MHz,
2-Phenyl-6H-thiazolo[5,4-e]indazole (Table 3, 3na): eluent,
1
petroleum ether/ethyl acetate = 3:1, (white solid 39.7 mg, 79%
1
DMSO) δ 8.10 – 8.02 (m, 3H), 7.85 (d, J = 10.5 Hz, 1H), 7.61
– 7.53 (m, 3H), 2.37 (s, 3H). 13C{1H} NMR (100 MHz, DMSO)
δ 169.2 (C-2), 160.60 (C6H2F)(d, J = 241.2 Hz), 153.2 (d, J =
12.4 Hz), 133.2, 132.0, 130.6, 129.9, 127.6, 124.1 (d, J = 23.8,
13.2 Hz), 108.8 (d, J = 24.6 Hz), 79.49 (m), 15.2 (CH3)(d, J =
3.7 Hz). HRMS (ESI) m/z calcd for C14H11FNS+ (M+H)+
244.0591, found 244.0590.
yield, mp = 259–260 °C), H NMR (400 MHz, DMSO) δ
13.58 (s, 1H), 8.41 (s, 1H), 8.12 – 8.09 (m, 2H), 8.04 (d, J =
9.0 Hz, 1H), 7.73 (d, J = 9.0 Hz, 1H), 7.59 (d, J = 7.0 Hz, 3H).
13C{1H} NMR (100 MHz, DMSO) δ 164.2 (C-2), 149.4, 138.3,
133.5, 133.2, 131.3, 129.9, 127.3, 127.9 (CHN), 121.9, 116.6,
110.7. HRMS (ESI) m/z calcd. for C14H10N3S+ (M+H)+
252.0590, found 252.0589.
7-Phenyl-1H-thiazolo[4,5-g]indazole (Table 3, 3ia) and 6-
Phenyl-1H-thiazolo[5,4-f]indazole (Table 3, 3ia’): eluent,
petroleum ether/ethyl acetate = 3:1, (white solid mixture 39.7
7-Phenylbenzo[1,2-d:4,3-d']bis(thiazole)-2-amine (Table 3,
3oa) and 6-Phenylbenzo[1,2-d:4,5-d']bis(thiazole)-2-amine
(Table 3, 3oa’): eluent, petroleum ether/ethyl acetate = 3:1,
(white solid mixture 42.5 mg, 75% yield, 4af/4af’ = 5:1, mp =
1
mg, 79% yield, 3ia/3ia’ = 10:1, mp = 262–263 °C), H NMR
1
(400 MHz, DMSO) δ 14.27 (s, 1H), 13.80 (s, 1H), 12.20 –
11.55 (m, 1H), 8.27 (d, J = 1.0 Hz, 1H), 8.16 (dd, J = 6.3, 2.9
Hz, 2H), 7.90 (d, J = 8.7 Hz, 1H), 7.86 (s, 1H), 7.82 (d, J = 8.7
Hz, 1H), 7.73 (d, J = 9.2 Hz, 1H), 7.63 – 7.58 (m, 3H), 7.37 (s,
1H). 13C{1H} NMR (100 MHz, DMSO) δ 166.5 (C-2), 153.7,
135.5, 134.8 (CHN), 133.3, 131.7, 130.0, 127.5, 120.8, 119.9,
116.9, 116.1. HRMS (ESI) m/z calcd for C14H10N3S+ (M+H)+
252.0590, found 252.0588.
139–140 °C), H NMR (400 MHz, DMSO) δ 8.37 (s, 1H),
8.11 – 8.00 (m, 3H), 7.92 (d, J = 8.7 Hz, 1H), 7.76 (d, J = 15.3
Hz, 2H), 7.56 (t, J = 12.1, 6.0 Hz, 5H). 13C{1H} NMR (100
MHz, DMSO) δ 166.8 (C-2), 164.0 (CNH2), 151.6, 150.0,
133.3, 131.5, 129.9, 127.4, 127.4, 127.1, 120.9 , 117.9. HRMS
(ESI) m/z calcd for C14H10N3S2 (M+H)+ 284.0311, found
+
284.0313.
Gram scale reaction for 3oa
2-Phenylnaphtho[1,2-d]thiazole (Table 3, 3ja)37: eluent,
petroleum ether/ethyl acetate = 20:1, (white solid 13.0 mg, 25%
yield, mp = 108–109 °C), 1H NMR (400 MHz, CDCl3) δ 8.96
(d, J = 8.2 Hz, 1H), 8.21 (dd, J = 7.9, 1.7 Hz, 2H), 7.94 (dd, J
= 15.9, 8.4 Hz, 2H), 7.81 (d, J = 8.7 Hz, 1H), 7.70 (dd, J = 8.2,
7.0 Hz, 1H), 7.60 (dd, J = 8.1, 7.0 Hz, 1H), 7.55 – 7.48 (m,
3H). 13C{1H} NMR (100 MHz, CDCl3) δ 167.0 (C-2), 150.4,
134.0 (C10H6), 132.1, 131.7, 130.6, 129.0, 128.8, 128.1, 127.3,
126.9, 126.1, 125.9, 124.0, 119.0.
6-Nitrobenzo[d]thiazol-2-amine (1o) (1.17 g, 6 mmol), phe-
nylmethanol (2a, 525 μL, 5 mmol), sulfur powder (480 mg,
15mmol) were added to a 40 mL oven-dried reaction vessel
and NMP (10 mL) were added by measuring cylinder, after Ar
collection process with displacement, the reaction was placed
o
in 160 C for 32 h. After cooling to room temperature, the
reaction was diluted with ethyl acetate (15 mL) and washed
with saturated salt water. The organic layer was separated and
the aqueous layer was extracted with ethyl acetate for three
times. The combined organic layer was dried over sodium
sulfate and the volatiles were removed under reduced pressure.
The residue was purified by column chromatography on silica
gel (petroleum ether/EtOAc = 5:1) to yield the desired product
3oa and 3oa’ as yellow solid mixture (1.23 g, 87% yield,
3oa/3oa’ = 11:1).
3-Methyl-7-phenyl-1H-thiazolo[4,5-g]indazole (Table 3, 3ka)
and 3-Methyl-6-phenyl-1H-thiazolo[5,4-f]indazole (Table 3,
3ka’): eluent, petroleum ether/ethyl acetate = 3:1, (white solid
mixture 42.4 mg, 80% yield, 3ka/3ka’ = 95:5, mp = 259–
1
260 °C), H NMR (400 MHz, DMSO) δ 13.96 (s, 1H), 13.37
(s, 1H), 8.18 – 8.11 (m, 2H), 7.80 (dd, J = 18.5, 8.6 Hz, 2H),
7.59 (s, 3H), 2.58 (s, 3H). 13C{1H} NMR (100 MHz, DMSO) δ
166.4 (C-2), 153.7, 143.2, 135.6 (CMeN), 133.4, 131.7, 129.9,
127.5, 120.0, 119.4, 116.0, 100.0, 12.3 (CH3). HRMS (ESI)
m/z calcd for C15H12N3S+ (M+H)+ 266.0746, found 266.0742.
ASSOCIATED CONTENT
Supporting Information
2-Phenylthiazolo[5,4-b]pyridin-5-amine (Table 3, 3la): elu-
ent, petroleum ether/ethyl acetate = 5:1, (white solid 24.1 mg,
53% yield, mp = 107–108 °C), 1H NMR (400 MHz, CDCl3) δ
8.05 – 7.95 (m, 3H), 7.51 – 7.44 (m, 3H), 6.63 (d, J = 8.8 Hz,
1H), 4.62 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3) δ 162.7
(C-2), 157.0 (C5H2NNH2), 156.6, 141.0, 133.9, 132.0, 130.5,
128.9, 126.9, 108.3. HRMS (ESI) m/z calcd for C12H10N3S+
(M+H)+ 228.0590, found 228.0588.
The Supporting Information is available free of charge on the
ACS Publications website.
Control experiments information, 1H NMR and 13C{1H}
NMR spectra for the products (PDF).
AUTHOR INFORMATION
Corresponding Author
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Copper-mediated C–H Activation/C–S Cross-coupling of Heterocy-
cles with Thiols. J. Org. Chem. 2011, 76, 8999-9007.
*Email: gjdeng@xtu.edu.cn.
*Email: zhangf@iccas.ac.cn.
(6) For selected examples, see: (a) Vásquez-Céspedes, S.; Ferry, A.;
Candish, L.; Glorius, F. Heterogeneously Catalyzed Direct C-H
Thiolation of Heteroarenes. Angew. Chem. Int. Ed. 2015, 44, 5772-
5776; (b) Tran, L. D.; Popov, I.; Daugulis, O. Copper-Promoted
Sulfenylation of sp2 C–H Bonds. J. Am. Chem. Soc. 2012, 134,
18237-18240.
ORCID
Guo-Jun Deng: 0000-0003-2759-0314
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENT
This work was supported by the National Natural Science
Foundation of China (21871226, 21572194), the Collaborative
Innovation Center of New Chemical Technologies for Envi-
ronmental Benignity and Efficient Resource Utilization, the
China Postdoctoral Science Foundation (2018M632976) and
the Hunan Provincial Innovative Foundation for Postgraduate
(CX2017B301).
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