Ru-catalyzed ortho-oxidative alkenylation of 2-arylbenzo[d]thiazoles in aqueous solution of anionic surfactant sodium dodecylbenzenesulfonate (SDBS)

Article abstract of DOI:10.1016/j.tet.2016.12.050

A mild and efficient Ru-catalyzed ortho-oxidative alkenylation of 2-arylbenzo[d]thiazoles through twofold C-H bond functionalization in aqueous solution of anionic surfactant sodium dodecylbenzenesulfonate (SDBS) has been developed using activated olefins as coupling partner. The protocol could be carried out smoothly on a gram scale, recyclable, and applicable to 2-arylthiazoles.

Full text of DOI:10.1016/j.tet.2016.12.050

Accepted Manuscript
Ru-catalyzed ortho-oxidative alkenylation of 2-arylbenzo[d]thiazoles in aqueous
solution of anionic surfactant sodium dodecylbenzenesulfonate (SDBS)
Yuanyuan Ping, Zhaobin Chen, Qiuping Ding, Qiang Zheng, Yuqing Lin, Yiyuan Peng
PII:
S0040-4020(16)31337-0
10.1016/j.tet.2016.12.050
TET 28342
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 November 2016
Revised Date: 17 December 2016
Accepted Date: 20 December 2016
Please cite this article as: Ping Y, Chen Z, Ding Q, Zheng Q, Lin Y, Peng Y, Ru-catalyzed ortho-
oxidative alkenylation of 2-arylbenzo[d]thiazoles in aqueous solution of anionic surfactant sodium
dodecylbenzenesulfonate (SDBS), Tetrahedron (2017), doi: 10.1016/j.tet.2016.12.050.
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ACCEPTED MANUSCRIPT
Ru-catalyzed ortho-oxidative alkenylation of 2-arylbenzo[d]thiazoles in aqueous
solution of anionic surfactant sodium dodecylbenzenesulfonate (SDBS)
Yuanyuan Ping, Zhaobin Chen, Qiuping Ding,* Qiang Zheng, Yuqing Lin,
Yiyuan Peng
Key Laboratory of Small Functional Organic Molecule, Ministry of Education and
Jiangxi’s Key Laboratory of Green Chemistry, Jiangxi Normal University, Nanchang,
Jiangxi 330022, China. E-mail: dqpjxnu@gmail.com
Abstract: A mild and efficient Ru-catalyzed ortho-oxidative alkenylation of
2-arylbenzo[d]thiazoles through twofold C-H bond functionalization in aqueous
solution of anionic surfactant sodium dodecylbenzenesulfonate (SDBS) has been
developed using activated olefins as coupling partner. The protocol could be carried
out smoothly on a gram scale, recyclable, and applicable to 2-arylthiazoles.
Graphical Abstract：
R'
R
R'
[RuCl2(p-cymene)]2 (10 mol%)
Cu(OAc)2 H2O (2.0 equiv)
R
S
N
S
N
KPF6 (20 mol%), SDBS (40 mol%)
H2O, 80oC, 24 h
+
R''O2C
CO2R''
28 examples
up to 96% yield
Keywords: Alkenylation; C–H functionalization; 2-Arylbenzo[d]thiazoles;
2-Arylthiazoles; Aqueous.
* Corresponding author： E-mail: dqpjxnu@gmail.com (Q. Ding).
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1. Introduction
Benzo[d]thiazoles are ubiquitous structural scaffolds in biologically natural products,
agrochemicals, and pharmaceuticals that exhibit remarkable antitumor, antiviral, and
antimicrobial activities.1 In particular, 2-arylbenzo[d]thiazoles are widely found in a
broad range of pharmaceutically active molecules.2 For example, aryl hydrocarbon
receptor agonist 2-(4-amino-3-methylphenyl)-5- fluorobenzothiazole (5F 203) can
induce oxidative stress triggering DNA damage and cytoglobin up-regulation in human
breast
cancer
cells
(Figure
1).2a
2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole (11C PIB), is an β-amyloid
PET imaging tracer for Alzheimer's disease diagnosis.2b In addition,
2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW 610) shows potent and selective
inhibitory activity against lung, colon, and breast cancer cell lines.2h
Figure 1 Selected bioactive examples containing 2-aryl-benzothiazole scaffold.
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Directing group-assisted transition-metal-catalyzed ortho C–H functionalization
reactions have been achieved considerable progress in organic and medicinal
chemistry in the past decades.3,4 To date, diverse functional groups including pyridine,
amide, anilide, imine, imidazoline, pyrazole, oxazoline, cyano, amine, carboxylic acid,
ester, ketone, and hydroxyl groups, have been used as directing groups for various
C–H bond functionalizations to construct various C–C and C–X (X = O, N, halogens)
bonds. Recently, we and other groups have reported many transition-metal-catalyzed
benzothiazole directed ortho C–H bond functionalization,4 including arylation,4a
alkylation,4b
acetoxylation,4c
halogenation,4d,e
amination,4f
acylation,4g-j
hydroxylation,4k,l nitration,4m trifluoromethylthiolation,4n and cyanation.4o
During the past decades, transition-metal-catalyzed C–H bond alkenylation
have emerged as powerful strategies for the step-economical synthesis of unsaturated
and conjugated molecules. In contrast, great success has been achieved with
expensive 4d transition-metal catalysts, such as rhodium5 or palladium6 complexes.
Recently, considerable progress has been made in this field through less expensive
ruthenium7-11 or iron12 species catalyzed C–H coupling reaction with alkenes, as
reported by Miura,7 Ackermann,8 Jeganmohan,9 Dixneuf,10 and Lei12b group.
It is well known that water is the ideal green solvent for organic reaction,
because of its abundance, nonflammable, nontoxic, and inexpensiveness. Furthermore,
great achievements showed that water could enhance the reactivities and selectivities
of some reactions.13 Given our recent interest in oxidative alkenylation-cyclization of
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aryl sulfonamides with acrylates,14 and the Suzuki-Miyaura coupling reaction15a and
the tandem synthesis 2-aminobenzothiazoles15b in aqueous, we would like to report
our recent efforts towards Ru-catalyzed ortho-oxidative alkenylation of
2-arylbenzo[d]thiazoles through twofold C–H bond functionalization in aqueous
solution of anionic surfactant sodium dodecylbenzenesulfonate (SDBS).
2. Results and Discussion
We commenced the dehydrogenative alkenylation of 2-(o-tolyl)benzo[d]thiazole (1a)
with butyl acrylate (2a) under the influence of Ru(II) catalyst, KPF6, and
Cu(OAc)2·H2O in aqueous (Table 1). To our delight, the desired coupling product 3a
was isolated in 14% yield in pure water (Table 1, entry 1). To improve the yield of 3a,
catalytic amount of poly(ethylene glycol) (PEG-200) as an additive was added into
the reaction. Expectively, the desired product 3a was improved to 30% (Table 1, entry
2). Screening of the oxidant indicated that AgOAc, Ag2CO3, K2S2O8, and CuBr were
inferior (Table 1, entries 3-6). Then, the effect of phase transfer catalysts (PTCs) was
examined (Table 1, entries 7-11). 18-Crown-6 exhibited the negative result (Table 1,
entry 7). Other PTCs, such as tetramethylammonium fluoride (TMAF), hexadecyl
trimethyl ammonium chloride (CTAC), sodium dodecyl sulfate (SDS), and sodium
dodecylbenzenesulfonate (SDBS) led to a low to moderate yield of the desired
product 3a (Table 1, entries 8-11). Among these PTCs, SDBS turned out to be the
best (Table 1, entry 11, 48%). Increasing the amount of Cu(OAc)2·H2O from 2.0
equiv to 3.0 and 4.0 equiv provided 3a in 60% and 84% yield, respectively (Table 1,
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entries 12 and 13). It is worthy to note that better result (90% yield) was achieved by
increasing the amount of SDBS (40 mol%) even in the presence of 2.0 equiv of
Cu(OAc)2·H2O (Table 1, entry 14). Switching to AgSbF6 as additive instead of KPF6
provided a lower yield (Table 1, entry 15, 60%). Further investigation indicated that
lowering reaction temperature also afforded a slightly lower yield of 3a (Table 1,
entry 16, 80%). In addition, we studied the reaction under catalytic amount of
Cu(OAc)2·H2O and using air as terminal oxidant to provide the desired product 3a in
lower yields (Table 1, entries 17 and 18)
Table
1
Optimization of Ru-catalyzed ortho-oxidative alkenylation of
2-(o-tolyl)benzo[d]thiazole 1a with butyl acrylate 2aa
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Entry
1
Oxidant (x equiv)
PTCc
-
Yield (%)b
14
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
AgOAc (2.0)
2
3
4
5
6
7
8
9
10
11
12
13
14d
15e
16f
17
18
PEG 200
PEG 200
PEG 200
PEG 200
PEG 200
18-Crown-6
TMAF
CTAC
SDS
30
20
25
Trace
Trace
Trace
35
25
22
48
60
84
90
60
80
43
16
Ag2CO3 (2.0)
K2S2O8 (2.0)
CuBr (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (3.0)
Cu(OAc)2·H2O (4.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (2.0)
Cu(OAc)2·H2O (0.5)
Cu(OAc)2·H2O (0.2)
SDBS
SDBS
SDBS
SDBS
SDBS
SDBS
SDBS
SDBS
a Reaction conditions: 2-(o-tolyl)benzo[d]thiazole 1a (0.2 mmol), butyl acrylate 2a
(0.4 mmol, 2.0 equiv), [RuCl2(p-cymene)]2 (10 mol%), additive (KPF6, 20 mol%),
phase transfer catalyst (PTC, 20 mol%), stirred at 80 oC for 24 h in H2O (2 mL).
b Yield based on 1a.
c
TMAF: tetramethylammonium fluoride; CTAC: hexadecyl trimethyl ammonium
chloride; SDS: sodium dodecyl sulfate; SDBS: sodium dodecylbenzenesulfonate.
d SDBS (40 mol%).
e Using AgSbF6 as additive instead of KPF6.
f At 60 oC.
With the optimal reaction conditions in hand, we next examined the scope of
2-arylbenzo[d]thiazoles for this Ru-catalyzed oxidative alkenylation in aqueous
(Scheme 1). In general, the alkenylation reaction carried out smoothly, providing the
6

ACCEPTED MANUSCRIPT
desired products in moderate to excellent yields. Both electron-rich as well as
electron-deficient 2-arylbenzo[d]thiazoles are suitable substrates. Different
substituents (methoxy, chloro, fluoro, and nitro) at the ortho position of the 2-aryl
group of substrates were worked well to afford various alkenylated products 3b-3e in
50-83% yield. The coupling of differently substituted 2-arylbenzo[d]thiazoles (R1 =
Me, F, and Cl) was found to be favored in this alkenylation to give desired products
3f-3l in 62-86% yields. This catalytic system was also compatible with
meta-substitued substrates providing only the mono-alkenylated products 3m-3q at
the less sterically hindered position in good yields. Subsequently, we examined the
coupling reaction of symmetrical substrates (R2 = 4-OMe, H) under the standard
reaction conditions, while we obtained a mono- and di-alkenylated products (3r-3t,
3r'-3t') in good yields with moderate regioselectivity.
Scheme 1 Ru-catalyzed ortho-oxidative alkenylation of 2-arylbenzo[d]thiazoles in
aqueousa,b
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a
Reaction conditions: 2-arylbenzo[d]thiazole 1 (0.2 mmol), butyl acrylate 2a (0.4
mmol, 2.0 equiv), [RuCl2(p-cymene)]2 (10 mol%), KPF6 (20 mol%), Cu(OAc)2·H2O
8

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(2.0 equiv), SDBS (40 mol%), H2O (2.0 mL), 80 oC, 24 h.
b Isolated yield.
Furthermore, we investigated the alkenylation of 1a with several functional alkenes
under optimal conditions (Scheme 2). Various acrylates 2b-2d performed smoothly to
give corresponding desired products 3u-3w in good yields (70-83%). Unfortunately,
the alkenylation of 1a with acrylonitrile 2e failed to offer the alkenlated product 3x
under the same conditions.
Scheme 2 Scope of alkenesa,b
Me
Me
[RuCl2(p-cymene)]2 (10 %)
Cu(OAc)2 H2O (2.0 equiv)
S
N
S
N
+
CO2R
KPF6 (20 %), SDBS (40 %)
H2O, 80oC, 24 h
(2.0 equiv)
RO2C
1a
2b-e
3
Me
Me
Me
Me
S
N
S
N
S
S
N
N
BuO2C
EtO2C
MeO2C
NC
3u, 83%
3v, 80%
3w, 70%
3x, trace
a
Reaction conditions: 2-(o-tolyl)benzo[d]thiazole 1a (0.2 mmol), acrylates 2b-e (0.4
mmol, 2.0 equiv), [RuCl2(p-cymene)]2 (10 mol%), KPF6 (20 mol%), Cu(OAc)2·H2O
(2.0 equiv), SDBS (40 mol%), H2O (2.0 mL), 80 oC, 24 h.
b Isolated yield.
Subsequently, we examined the alkenylation of 2-arylthiazoles 4 with n-butyl
acrylate 2a under the same conditions (Scheme 3). Notably, 2-(o-tolyl)thiazole 4a
was found to undergo the coupling reaction to afford desired product 5a in 85% yield.
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Interesting, to 2-(m-tolyl)thiazole 4c with a methyl group at the meta-position of
2-phenyl ring gave product 5c selectively at the less sterically hindered position in
excellent yield (92%). To those para-position substituted or unsubstituted
2-phenylthiazoles 4d and 4e also reacted with 2a smoothly under the present
conditions and led to the mixtures of mono- and di-alkenylated products 5d(5d') and
5e(5e') in high yields with moderate selectivity.
Scheme 3 Ru-catalyzed ortho-oxidative alkenylation of 2-arylthiazoles in aqueousa,b
R
[RuCl2(p-cymene)]2 (10 mol%)
Cu(OAc)2 H2O (2.0 equiv)
S
N
R
S
N
n
+
CO2 Bu
KPF6 (20 mol%), SDBS (40 mol%)
H2O, 80oC, 24 h
(2.0 equiv)
2a
nBuO2C
4a-e
Me
5a-e
MeO
Me
S
S
S
N
S
S
Me
N
N
N
N
nBuO2C
nBuO2C
nBuO2C
nBuO2C
nBuO2C
5d 96%
mono/di = 9/7
5e 88%
mono/di = 4/7
5a 85%
5b 83%
5c 92%
a
Reaction conditions: 2-arylthiazoles 4 (0.3 mmol), n-butyl acrylate 2a (0.6 mmol,
2.0 equiv), [RuCl2(p-cymene)]2 (10 mol%), KPF6 (20 mol%), Cu(OAc)2·H2O (2.0
equiv), SDBS (40 mol%), H2O (2.0 mL), 80 oC, 24 h.
b Isolated yield.
To further investigate the scalability of the present reaction, we proceeded to run a
gram-scale reaction of the 2-(o-tolyl)benzo[d]thiazole 1a with n-butyl acrylate 2a
(Scheme 4). The alkenylated product 3a was obtained in 94% isolated yield when the
reaction was scaled by 25 times to 5.0 mmol.
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Scheme 4 Gram-Scale Synthesis
To check the reusability of the reaction medium and catalytic system, the
akenylation of 2-(o-tolyl)benzo[d]thiazole 1a with n-butyl acrylate 2a was studied
under the standard conditions (Scheme 5). We observed that this Ru-catalytic system
could be recycled three times without obviously loss of activity.
Scheme 5 Recycle of the catalytic system
Recycle
1
87
2
86
3
80
4
50
Yield (%)a,b
a
Reaction conditions: 2-(o-tolyl)benzo[d]thiazole 1a (1.0 mmol, 225 mg), butyl
acrylate 2a (2.0 mmol, 290 ul), [RuCl2(p-cymene)] (10 mol%, 61 mg),
Cu(OAc)2·H2O (2.0 mmol, 399 mg), KPF6 (20 mol%, 37 mg), SDBS (20 mol%, 140
mg), H2O (10.0 mL), 80 oC, 24 h.
b Isolated yield.
Based on the previous results,7-11 the mechanism of ruthenium-catalyzed oxidative
C–H bond alkenylation may involve the following steps (Scheme 6): (і) ortho-C–H
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bond activation in the presence of ruthenium( ) complexes I to form the
cyclometallated intermediate; ( ) the coordinative insertion of alkene 2 into the
metallacycle to give the seven-membered Ru( )-cycle II; ( ) β-hydride elimination
to afford the desired alkenlated product 3 and Ru(0); ( ) the reoxidation of Ru(0) by
Cu( ) to regenerate the active cationic catalyst Ru( ).
Scheme 6 Possible Mechanism of the Alkenylation
R'
CuOAc
Cu(OAc)2
S
N
Ru(II)
1
Ru(0)
C-H activation
R'
S
N
R'
S
RO2C
Reductive elimination
3
N
Ru
R'
I
S
Coordinative
insertion
N
Ru
CO2R
CO2R
2
II
3. Conclusions
In summary, we have developed a highly efficient ruthenium( )-catalyzed
regioselective ortho-C–H bond alkenylation of variety of substituted
a
2-arylbenzo[d]thiazoles and 2-arylthiazoles with diverse acrylates. The conditions are
mild simply with water as a green reaction medium in the presence of catalytic
o
amount of anionic surfactant SDBS at 80 C, and using commercially available and
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inexpensive Cu(OAc)2·H2O as oxidant. In addition, the catalytic system could be
carried out smoothly on a gram scale.
4. Experimental
4.1 General procedure for ruthenium-catalyzed ortho-oxidative alkenylation of
2-arylbenzo[d]thiazoles 1 in aqueous solution of anionic surfactant sodium
dodecylbenzenesulfonate (SDBS)
A suspension of 2-arylbenzo[d]thiazoles 1 (0.2 mmol), acrylates 2 (0.4 mmol, 2.0
equiv), [RuCl2(p-cymene)]2 (12.2 mg, 10 mol%), KPF6 (7.4 mg, 20 mol%),
Cu(OAc)2·H2O (79.8 mg, 2.0 equiv), and SDBS (27.8 mg, 40 mol%) in H2O (2.0 mL)
o
was stirred at 80 C under air for 24 h. After that, the solution was extracted with
EtOAc. The combined organic phase was dried with MgSO4 and concentrated under
reduced pressure. The residue was purified by column chromatography on silica gel
(Petroleum ether/EtOAc: 10/1) to yield alkenlated product 3.
4.1.1 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-3-methylphenyl)acrylate 3a. Yellow oil
(90%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.13 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.57 (dd, J = 9.5, 4.4 Hz, 1H), 7.54
(s, 1H), 7.53 – 7.48 (m, 1H), 7.48 – 7.42 (m, 1H), 7.40 (t, J = 7.7 Hz, 1H), 7.33 (d, J =
7.6 Hz, 1H), 6.36 (d, J = 15.8 Hz, 1H), 4.06 (t, J = 6.5 Hz, 2H), 2.25 (s, 3H), 1.58 –
1.48 (m, 2H), 1.26 (d, J = 15.1 Hz, 2H), 0.81 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 166.4, 165.2, 153.3, 141.8, 138.2, 136.3, 134.6, 133.9, 131.7, 129.9, 126.2,
125.4, 123.9, 123.6, 121.5, 120.5, 64.2, 30.5, 20.1, 19.0, 13.5; HRMS (ESI): m/z [M +
H]+ calcd for C21H22NO2S: 352.1366; found: 352.1356.
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4.1.2 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-3-methoxyphenyl)acrylate 3b. Pale yellow
oil (50%); Rf = 0.2 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3)
δ 8.13 (d, J = 8.1 Hz, 1H), 7.93 (d, J = 7.9 Hz, 1H), 7.75 (d, J = 15.9 Hz, 1H), 7.55 –
7.39 (m, 3H), 7.35 (d, J = 7.8 Hz, 1H), 7.05 (d, J = 8.2 Hz, 1H), 6.39 (d, J = 15.9 Hz,
1H), 4.10 (t, J = 6.5 Hz, 2H), 3.84 (s, 3H), 1.56 (d, J = 8.0 Hz, 2H), 1.32 (dd, J = 15.1,
13
7.5 Hz, 2H), 0.85 (t, J = 7.4 Hz, 3H); C NMR (100 MHz, CDCl3) δ 166.6, 162.4,
157.9, 153.0, 142.6, 136.5, 136.3, 131.1, 125.9, 125.3, 123.6, 123.2, 121.3, 120.8,
119.3, 112.3, 64.3, 56.0, 30.6, 19.1, 13.6; HRMS (ESI): m/z [M + H]+ calcd for
C21H22NO3S: 368.1315; found: 368.1315.
4.1.3 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-3-chlorophenyl)acrylate 3c. Pale yellow
oil (65%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3)
δ 8.16 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.56 (t, J
= 8.6 Hz , 2H), 7.43-7.50 (m, 3H), 6.38 (d, J = 16.0 Hz, 1H), 4.07 (t, J = 6.4 Hz, 2H),
1.50-1.57 (m, 2H), 1.22-1.29 (m, 2H), 0.81 (t, J = 6.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 166.1, 162.6, 153.1, 140.7, 140.0, 136.4, 135.0, 133.1, 131.0, 130.9, 126.4,
125.8, 124.9, 124.0, 122.0, 121.6, 64.5, 30.6, 19.1, 13.6; HRMS (ESI): m/z [M + H]+
calcd for C20H19ClNO2S: 372.0820; Found: 372.0820.
4.1.4 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-3-fluorophenyl)acrylate 3d. Pale yellow oil
(83%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
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8.16 (dd, J = 0.6, 7.8 Hz, 1H), 7.95 (dd, J = 0.8, 8.0 Hz, 1H), 7.91 (d, J = 15.6 Hz,
1H), 7.54 (t, J = 8.0 Hz, 2H), 7.44-7.50 (m, 2H), 7.26 ( dt, J = 1.2, 8.4 Hz, 1H), 6.43
(d, J = 16.0 Hz, 1H), 4.14 (t, J = 6.6 Hz, 2H), 1.56-1.62 (m, 2H), 1.31-1.36 (m, 2H),
0.87 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.3, 160.6 (d, 1JC-F = 250.8
Hz), 159.2, 153.1, 141.6 (d, 4JC-F = 2.4 Hz), 136.9 (d, 4JC-F = 1.8 Hz), 136.3 (d, 3JC-F
=
=
4
9.5 Hz), 131.5, 131.4, 126.3, 125.8, 123.9, 123.0 (d, JC-F = 3.9 Hz), 121.9 (d, 3JC-F
8.2 Hz), 121.4,13.7, 117.0 (d, 2JC-F = 22.0 Hz), 64.5, 30.7, 19.2; HRMS (ESI): m/z [M
+ H]+ calcd for C20H19FNO2S: 356.1115; Found: 356.1115.
4.1.5 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-3-nitrophenyl)acrylate 3e. Purple oil
(61%); Rf = 0.5 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.10 (dd, J = 13.5, 8.1 Hz, 2H), 7.96 (t, J = 8.0 Hz, 2H), 7.69 (t, J = 8.1 Hz, 1H), 7.53
(ddd, J = 26.0, 11.2, 5.6 Hz, 3H), 6.44 (d, J = 15.9 Hz, 1H), 4.10 (t, J = 6.5 Hz, 2H),
1.59 – 1.50 (m, 2H), 1.29 (s, 2H), 0.82 (d, J = 7.4 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 165.6, 160.3, 153.1, 150.0, 139.3, 137.2, 136.4, 130.9, 130.8, 128.4, 126.6,
126.0, 125.4, 124.0, 123.6, 121.6, 64.7, 30.5, 19.0, 13.6; HRMS (ESI): m/z [M + H]+
calcd for C20H19N2O4S: 383.1060; Found: 383.1069.
4.1.6 (E)-butyl 3-(3-chloro-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)acrylate 3f. Pale
yellow oil (62%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 7.95 (d, J = 8.8 Hz, 1H), 7.66 (s, 1H), 7.56 (d, J = 7.2 Hz, 1H), 7.44 (d, J =
6.8 Hz, 1H), 7.36-7.40 (m, 2H), 7.28 ( d, J = 8.4 Hz, 1H), 6.45 (dd, J = 4.8, 15.6 Hz,
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ACCEPTED MANUSCRIPT
1H), 3.99 (t, J = 5.6 Hz, 2H), 2.45 (s, 3H), 1.42-1.47 (m, 2H), 1.14-1.25 (m, 2H), 0.74
(t, J = 6.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.1, 161.4, 151.3, 140.8, 136.9,
136.6, 136.0, 135.0, 133.3, 130.9, 130.8, 128.0, 124.9, 123.4, 121.9, 121.2, 64.5, 30.6,
21.6, 19.1, 13.6; HRMS (ESI): m/z [M + H]+ calcd for C21H21ClNO2S: 386.0976;
Found: 386.0986.
4.1.7 (E)-butyl 3-(3-chloro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)acrylate 3g. Pale
yellow oil (86%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.10-8.12 (m, 1H), 7.66 (t, J = 7.4 Hz 2H), 7.55 (d, J = 8.0 Hz, 1H),
7.44-7.48 (m, 2H), 7.31 (t, J = 8.8 Hz, 1H), 6.40 (d, J = 16.4 Hz, 1H), 4.09 (t, J = 6.0
Hz, 2H), 1.56 (t, J = 6.0 Hz, 2H), 1.25-1.30 (m, 2H), 0.82-0.86 (m, 3H),; 13C NMR
4
1
(100 MHz, CDCl3) δ 166.0, 162.3 (d, JC-F = 3.2 Hz), 160.8 (d, JC-F = 245.0 Hz),
149.7 (d, 3JC-F = 11.5 Hz), 140.5, 137.5 (d, 3JC-F = 11.7 Hz), 136.9, 134.9, 132.7, 131.2,
4
2
130.9, 125.0, 125.0 (d, JC-F = 2.5 Hz), 122.1, 115.2 (d, JC-F = 24.7 Hz), 107.7 (d,
2JC-F = 27.0 Hz), 64.5, 30.6, 19.1, 13.6; HRMS (ESI): m/z [M + H]+ calcd for
C20H18ClFNO2S: 390.0725; Found: 390.0731.
4.1.8 (E)-butyl 3-(3-fluoro-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)acrylate 3h. Pale
yellow oil (80%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.03 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 16.0 Hz, 1H), 7.72 (s, 1H), 7.52 (d, J =
7.6 Hz, 1H), 7.44-7.47 (m, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.21 (t, J = 8.8 Hz, 1H),
6.41 (d, J = 15.6 Hz, 1H), 4.14 (t, J = 6.2 Hz, 2H), 2.51 (s, 3H), 1.58-1.63 (m, 2H),
16

ACCEPTED MANUSCRIPT
1.26-1.37 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.3,
1
4
161.6 (d, JC-F = 249.6 Hz), 158.1, 151.3, 141.7 (d, JC-F = 3.4 Hz), 136.9, 136.5 (d,
4JC-F = 2.4 Hz), 136.0, 131.3 (d, 3JC-F = 9.1 Hz), 128.0, 123.4, 123.0 (d, 4JC-F = 3.9 Hz),
2
122.2, 121.7, 121.0, 116.9 (d, JC-F = 22.2 Hz), 64.4, 30.7, 21.6, 19.2, 13.7; HRMS
(ESI): m/z [M + H]+ calcd for C21H21FNO2S: 370.1272; Found: 370.1277.
4.1.9 (E)-butyl 3-(2-(6-chlorobenzo[d]thiazol-2-yl)-3-fluorophenyl)acrylate 3i. Pale
yellow oil (83%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 0.89 (t, J = 7.4 Hz, 3H), 1.26-1.38 (m, 2H), 1.58-1.65 (m, 2H), 2.24 (s, 3H),
4.15 (t, J = 6.4 Hz, 2H), 6.42 (d, J = 15.6 Hz, 1H), 7.25 (d, J = 9.0 Hz, 1H), 7.47-7.58
(m,3H), 7.90-7.93 (m, 2H), 8.06 (d, J = 8.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ
2
3
13.7, 19.2, 30.7, 64.5, 117.0 (d, JC-F = 22.4 Hz), 121.0, 121.4 (d, JC-F = 15.0 Hz),
122.0, 123.2 (d, 4JC-F = 4.0 Hz), 124.6, 127.2, 131.7 (d, 3JC-F = 9.0 Hz), 131.9, 136.9,
4
1
137.4, 141.5 (d, JC-F = 3.0 Hz), 151.5, 159.8, 160.5 (d, JC-F = 250.1 Hz), 166.3;
HRMS (ESI): m/z [M + H]+ calcd for C20H18ClFNO2S: 390.0725; Found: 370.0729.
4.1.10 (E)-butyl 3-(3-fluoro-2-(6-fluorobenzo[d]thiazol-2-yl)phenyl)acrylate 3j. Pale
yellow oil (79%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 0.88 (dt, J = 2.0, 7.4 Hz, 3H), 1.25-1.38 (m, 2H), 1.59-1.63 (m, 2H), 4.15
(dt, J = 2.2, 6.4 Hz, 2H), 6.43 (dd, J = 2.2, 16.0 Hz, 1H), 7.24-7.30 (m, 2H), 7.48-7.50
(m, 1H), 7.55 (d, J = 8.0Hz, 1H), 7.63 (d, J = 8.0Hz, 1H), 7.90 (dt, J = 1.8, 15.6 Hz,
1H ), 8.08-8.10 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 13.7, 19.2, 30.7, 64.5, 107.5
17

ACCEPTED MANUSCRIPT
2
2
(d, JC-F = 27.0 Hz), 115.2(d, JC-F = 24.6 Hz), 116.9 (d, 2JC-F = 22.4 Hz), 121.5 (d,
4
3
3JC-F = 13.8 Hz), 121.9, 123.1 (d, JC-F = 2.7 Hz), 124.9 (d, JC-F = 9.5 Hz), 131.6 (d,
4
4
3JC-F = 9.8 Hz), 136.9 (d, JC-F = 2.0 Hz), 137.2, 137.4 (d, JC-F = 3.2 Hz), 141.5 (d,
4
4
1
4JC-F = 3.0 Hz), 149.7 (d, JC-F = 1.5 Hz), 159.0 (d, JC-F = 3.4 Hz), 160.5 (d, JC-F
=
1
250.7 Hz), 160.5 (d, JC-F = 246.3 Hz), 166.3; HRMS (ESI): m/z [M + H]+ calcd for
C20H18F2NO2S: 374.1021; Found: 374.1021.
4.1.11 (E)-butyl 3-(2-(6-chlorobenzo[d]thiazol-2-yl)-3-methylphenyl)acrylate 3k.
Yellow oil (78%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.03 (d, J = 8.7 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H),
7.53 – 7.44 (m, 2H), 7.41 (t, J = 7.7 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 6.36 (d, J =
15.8 Hz, 1H), 4.08 (t, J = 6.5 Hz, 2H), 2.24 (s, 3H), 1.55 (dt, J = 14.5, 6.6 Hz, 2H),
13
1.27 – 1.22 (m, 2H), 0.83 (t, J = 7.4 Hz, 3H); C NMR (100 MHz, CDCl3) δ 166.4,
165.8, 151.8, 141.6, 138.2, 137.5, 134.6, 133.4, 131.7, 131.6, 130.1, 127.1, 124.4,
124.0, 121.1, 120.7, 64.3, 30.6, 20.1, 19.1, 13.6; HRMS (ESI): m/z [M + H]+ calcd for
C21H21ClNO2S: 386.0976; Found: 386.0984.
4.1.12 (E)-butyl 3-(2-(6-fluorobenzo[d]thiazol-2-yl)-3-methylphenyl)acrylate 3l.
Yellow oil (85%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.06-8.09 (m, 1H), 7.58-7.63 (m, 2H), 7.50 (d, J = 16.0 Hz, 1H), 7.41 (t, J =
7.6 Hz, 1H), 7.27-7.35 (m, 2H), 6.37 (d, J = 16.0 Hz, 1H), 4.08 (t, J = 6.6 Hz, 2H),
2.25 (s, 3H), 1.50-1.58 (m, 2H), 1.24-1.29 (m, 2H), 0.83 (t, J = 7.2Hz, 3H); 13C NMR
18

ACCEPTED MANUSCRIPT
4
1
(100 MHz, CDCl3) δ 166.5, 165.0 (d, JC-F = 3.0 Hz), 160.7 (d, JC-F = 244.9 Hz),
150.0 (d, 4JC-F = 1.5 Hz), 141.7, 138.3, 137.4 (d, 3JC-F = 10.9 Hz), 134.6, 133.6, 131.8,
3
2
130.1, 124.7 (d, JC-F = 9.6 Hz), 124.0, 120.7, 115.0 (d, JC-F = 24.4 Hz), 107.7 (d,
2JC-F = 25.6 Hz), 64.3, 30.6, 20.2, 19.1, 13.6; HRMS (ESI): m/z [M + H]+ calcd for
C21H21FNO2S: 370.1272; Found: 370.1272.
4.1.13 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-4-methylphenyl)acrylate 3m. Yellow oil
(75%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.31(d, J = 16.0 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 7.6 Hz, 1H), 7.54 (d, J
= 8.8 Hz, 2H), 7.42 (t, J = 7.0 Hz, 1H), 7.32 (t, J = 7.2 Hz, 1H), 7.20 (d, J =7.6 Hz,
1H), 6.34 (d, J = 16.0 Hz, 1H), 4.10 (t, J = 6.6 Hz, 2H), 2.33 (s, 3H), 1.53-1.58 (m,
2H), 1.28-1.37 (m, 2H), 0.83 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.9,
166.4, 153.9, 143.0, 140.3, 135.9, 133.3, 131.5, 131.3, 127.7, 126.4, 125.4, 123.7,
121.4, 120.1, 64.3, 30.8, 21.3, 19.2, 13.7; HRMS (ESI): m/z [M + H]+ calcd for
C21H22NO2S: 352.1366; Found: 352.1369.
4.1.14 (E)-butyl 3-(2-(6-chlorobenzo[d]thiazol-2-yl)-4-methylphenyl)acrylate 3n.
Yellow oil (82%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.31 (d, J =16.0 Hz, 1H), 7.95 (d, J = 8.2 Hz, 1H), 7.81 (s, 1H), 7.53-7.57
(m, 2H), 7.39 (d, J = 8.8 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 6.35 (d, J = 16.0 Hz, 1H),
4.12 (t, J = 6.2 Hz, 2H), 2.36 (s, 3H), 1.55-1.62 (m, 2H), 1.18-1.37 (m, 2H), 0.86 (t, J
= 7.2 Hz, 3H),; 13C NMR (100 MHz, CDCl3) δ 167.0, 166.8, 152.4, 142.8, 140.4,
19

ACCEPTED MANUSCRIPT
136.9, 132.8, 131.5, 131.4, 131.3, 127.8, 127.2, 124.4, 121.0, 120.3, 64.4, 30.8, 21.3,
19.2,13.7; HRMS (ESI): m/z [M + H]+ calcd for C21H21ClNO2S: 386.0976; Found:
386.0976.
4.1.15 (E)-butyl 3-(2-(6-fluorobenzo[d]thiazol-2-yl)-4-methylphenyl)acrylate 3o.
Yellow oil (72%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.38 (d, J = 16.0 Hz , 1H), 8.05-8.07 (m, 1H), 7.64 (d, J = 7.2 Hz, 1H), 7.60
(s, 2H), 7.30 (d, J = 7.6 Hz, 1H), 7.24 (d, J = 9.2 Hz, 1H), 6.43 (d, J = 16.0 Hz, 1H),
4.19 (s, 2H), 2.44 (s, 3H), 1.65 (t, J = 4.8 Hz, 2H), 1.42 (d, J = 6.4 Hz, 2H), 0.93 (dt, J
4
= 1.6, 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.9, 166.2 (d, JC-F = 2.6 Hz),
1
4
3
160.6 (d, JC-F = 244.8 Hz), 150.6 (d, JC-F = 1.4 Hz), 142.9, 140.4, 136.8 (d, JC-F
=
4
3
10.9 Hz), 133.0, 131.4 (d, JC-F = 6.3 Hz), 131.2, 127.8, 124.7 (d, JC-F = 8.4 Hz),
2
120.2, 115.1 (d, JC-F = 24.2 Hz), 107.7, 107.5, 64.4, 30.8, 21.3, 19.2, 13.8; HRMS
(ESI): m/z [M + H]+ calcd for C21H21FNO2S: 370.1272; Found: 370.1272.
4.1.16 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-4-chlorophenyl)acrylate 3p. Colorless oil
(69%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.35 (d, J = 15.9 Hz, 1H), 8.14 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.84 (d, J
= 2.1 Hz, 1H), 7.67 (d, J = 8.5 Hz, 1H), 7.55 (dd, J = 11.3, 4.1 Hz, 1H), 7.51 – 7.39
(m, 2H), 6.44 (d, J = 15.9 Hz, 1H), 4.20 (t, J = 6.6 Hz, 2H), 1.69 – 1.63 (m, 2H), 1.43
13
(dt, J = 14.9, 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H); C NMR (100 MHz, CDCl3) δ
166.5, 164.5, 153.8, 141.9, 135.8, 135.7, 134.7, 132.5, 130.7, 130.4, 129.1, 126.6,
20

ACCEPTED MANUSCRIPT
125.8, 123.9, 121.5, 121.4, 64.5, 30.7, 19.2, 13.7; HRMS (ESI): m/z [M + H]+ calcd
for C20H19ClNO2S: 372.0820; Found: 372.0820.
4.1.17 (E)-butyl 3-(4-chloro-2-(6-methylbenzo[d]thiazol-2-yl)phenyl)acrylate 3q. Pale
yellow oil (45%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.35 (d, J = 16.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.82 (s, 1H), 7.71 (s,
1H), 7.65 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 8.4 Hz, 1H), 6.43
(d, J = 16.0 Hz, 1H), 4.20 (t, J = 6.2 Hz, 2H), 2.51 (s, 3H), 1.64-1.71 (m, 2H),
1.39-1.45 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.5,
163.5, 152.0, 142.1, 136.1, 136.1, 135.7, 134.9, 132.5, 130.6, 130.3, 129.1, 128.3,
123.4, 121.4, 121.2, 64.5, 30.8, 21.6, 19.2, 13.8; HRMS (ESI): m/z [M + H]+ calcd for
C21H21ClNO2S: 386.0976; Found: 386.0982.
4.1.18 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)-5-methoxyphenyl)acrylate 3r(mono).
1
Colorless oil (40%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); H NMR (400
MHz, CDCl3) δ 8.49 (d, J = 16.0 Hz, 1H), 8.10 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0
Hz, 1H), 7.79 (d, J = 8.4 Hz, 1H), 7.45 (s, 1H), 7.40 (d, J = 7.6 Hz, 1H), 7.20 (s, 1H),
7.02 (d, J = 7.6 Hz, 1H), 6.45 (d, J = 16.0 Hz, 1H), 4.22 (d , J = 6.0 Hz, 2H), 3.90 (s,
13
3H), 1.68 (s, 2H), 1.44 (t, J = 6.6 Hz, 2H), 0.94 (t, J = 7.2 Hz, 3H); C NMR (100
MHz, CDCl3) δ 166.7, 166.2, 161.0, 154.0, 143.4, 135.6, 132.6, 126.3, 126.2, 125.2,
123.5, 121.3, 121.2, 115.8, 112.6, 64.5, 55.6, 30.8, 19.2, 13.7; HRMS (ESI): m/z [M +
H]+ calcd for C21H22NO3S: 368.1315; Found: 368.1318.
21

ACCEPTED MANUSCRIPT
4.1.19
(2E,2'E)-dibutyl
3,3'-(2-(benzo[d]thiazol-2-yl)-5-methoxy-1,3-phenylene)diacrylate 3r(di). Colorless
oil (20%); Rf = 0.2 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3)
δ 8.14 (d, J = 7.6 Hz, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.55-7.59 (m, 3H), 7.46 (s, 1H),
7.25 (s, 2H), 6.38 (d, J = 15.6 Hz, 2H), 4.09 (d, J = 3.2 Hz, 4H), 3.93 (s, 3H), 1.26 (s,
8H), 0.82-0.88 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 166.2, 163.3, 160.6, 141.4,
136.9, 136.7, 127.0, 126.5, 125.7, 123.9, 121.6, 121.4, 113.2, 64.5, 55.7, 30.6, 19.1,
13.6; HRMS (ESI): m/z [M + H]+ calcd for C28H32NO5S: 494.1995; Found: 494.1996.
4.1.20 (E)-butyl 3-(2-(benzo[d]thiazol-2-yl)phenyl)acrylate 3s(mono). Pale yellow oil
(50%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.38 (d, J = 16.0 Hz, 1H), 8.08 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.68-7.78
(m, 2H), 7.43-7.49 (m, 3H), 7.37 (t, J = 7.6 Hz, 1H), 6.41 (d, J = 16.0 Hz, 1H), 4.14 (t,
J = 6.4 Hz, 2H), 1.59-1.63 (m, 2H), 1.34-1.39 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 166.7, 166.3, 154.0, 143.2, 135.9, 134.1, 133.4, 131.0,
130.4, 129.9, 127.8, 126.4, 125.5, 123.8, 121.4, 121.1, 64.4, 30.8, 19.2, 13.7; HRMS
(ESI): m/z [M + H]+ calcd for C20H20NO2S: 338.1209; Found: 338.1214.
4.1.21 (2E,2'E)-dibutyl 3,3'-(2-(benzo[d]thiazol-2-yl)-1,3-phenylene)diacrylate 3s(di).
Pale yellow oil (30%); Rf = 0.2 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400
MHz, CDCl3) δ 8.16 (d, J = 8.0 Hz, 1H), 7.95 (d, J = 8.4 Hz, 1H), 7.77 (d, J = 7.6 Hz,
22

ACCEPTED MANUSCRIPT
2H), 7.53-7.59 (m, 4H), 7.49 (t, J = 7.4 Hz, 1H), 6.40 (d, J = 16.0 Hz, 2H), 4.09 (t, J =
6.8 Hz, 4H), 1.51-1.58 (m, 4H), 1.25-1.29 (m, 4H), 0.75 (t, J = 7.8 Hz, 6H); 13C NMR
(100 MHz, CDCl3) δ 166.2, 163.2, 153.2, 141.2, 136.5, 135.5, 134.1, 130.4, 127.8,
126.6, 125.9, 124.0, 121.6, 121.5, 64.4, 30.6, 19.1, 13.6; HRMS (ESI): m/z [M + H]+
calcd for C27H30NO4S: 464.1890; Found: 464.1890.
4.1.22 (E)-butyl 3-(2-(6-methylbenzo[d]thiazol-2-yl)phenyl)acrylate 3t(mono). Yellow
oil (60%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3)
δ 8.43 (d, J = 15.9 Hz, 1H), 8.01 (d, J = 8.3 Hz, 1H), 7.87 – 7.79 (m, 1H), 7.76 – 7.70
(m, 2H), 7.49 (dd, J = 5.8, 3.4 Hz, 2H), 7.33 (dd, J = 8.4, 1.2 Hz, 1H), 6.46 (d, J =
15.9 Hz, 1H), 4.20 (t, J = 6.6 Hz, 2H), 2.52 (s, 3H), 1.72 – 1.64 (m, 2H), 1.42 (dq, J =
14.7, 7.4 Hz, 2H), 0.94 (t, J = 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.8,
165.2, 152.1, 143.3, 136.0, 135.7, 134.0, 133.5, 130.9, 130.2, 129.8, 128.0, 127.7,
123.3, 121.1, 120.9, 64.4, 30.8, 21.6, 19.2, 13.7; HRMS (ESI): m/z [M + H]+ calcd for
C21H21NO2S: 352.1366; found: 352.1373.
4.1.23
(2E,2'E)-dibutyl
3,3'-(2-(6-methylbenzo[d]thiazol-2-yl)-1,3-phenylene)diacrylate 3t(di). Orange oil
(30%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.02 (d, J = 8.3 Hz, 1H), 7.74 (t, J = 7.4 Hz, 3H), 7.60 – 7.51 (m, 3H), 7.37 (dd, J =
8.4, 1.3 Hz, 1H), 6.39 (d, J = 15.9 Hz, 2H), 4.08 (t, J = 6.5 Hz, 4H), 2.54 (s, 3H), 1.54
13
(dd, J = 14.7, 6.8 Hz, 4H), 1.32 – 1.16 (m, 4H), 0.83 (t, J = 7.4 Hz, 6H); C NMR
23

ACCEPTED MANUSCRIPT
(100 MHz, CDCl3) δ 166.2, 162.0, 151.4, 141.3, 136.7, 136.0, 135.5, 134.2, 130.2,
128.2, 127.8, 123.4, 121.4, 121.1, 64.4, 30.6, 21.6, 19.1, 13.6; HRMS (ESI): m/z [M +
H]+ calcd for C28H31NO4S: 478.2046; found: 478.2054.
4.1.24 (E)-tert-butyl 3-(2-(benzo[d]thiazol-2-yl)-3-methylphenyl)acrylate 3u.
1
Colorless oil (83%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); H NMR (400
MHz, CDCl3) δ 8.13 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.63 – 7.49 (m, 2H),
7.50 – 7.35 (m, 3H), 7.32 (d, J = 7.6 Hz, 1H), 6.32 (d, J = 15.8 Hz, 1H), 2.24 (s, 3H),
1.39 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 165.8, 165.4, 153.3, 140.8, 138.2, 136.4,
134.7, 134.0, 131.5, 129.9, 126.3, 125.5, 123.8, 123.7, 122.2, 121.5, 80.4, 28.1, 20.2;
HRMS (ESI): m/z [M + H]+ calcd for C21H22NO2S: 374.1185; Found: 374.1185.
4.1.25 (E)-ethyl 3-(2-(benzo[d]thiazol-2-yl)-3-methylphenyl)acrylate 3v. Yellow oil
(80%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.14 (d, J = 7.6 Hz, 1H), 7.95 (d, J = 7.6 Hz, 1H), 7.57 (t, J = 8.2Hz, 2H), 7.52 (d, J =
7.6 Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 7.6 Hz,
1H), 6.36 (d, J = 16.0 Hz, 1H), 4.13 (d, J = 7.2 Hz, 2H), 2.25 (s, 2H), 1.21 (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.4, 165.3, 153.4, 142.0, 138.3, 136.4,
134.6, 134.0, 131.7, 129.9, 126.3, 125.5, 124.0, 123.7, 121.6, 120.6, 60.4, 20.2, 14.2;
HRMS (ESI): m/z [M + H]+ calcd for C19H18NO2S: 324.1053; Found: 324.1053.
4.1.26 (E)-methyl 3-(2-(benzo[d]thiazol-2-yl)-3-methylphenyl)acrylate 3w. Yellow oil
24

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(70%); Rf = 0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.14 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 7.9 Hz, 1H), 7.61 – 7.37 (m, 5H), 7.34 (d, J =
7.6 Hz, 1H), 6.37 (d, J = 15.8 Hz, 1H), 3.67 (s, 3H), 2.24 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 166.9, 165.2, 153.3, 142.1, 138.4, 136.4, 134.5, 133.9, 131.8, 129.9,
126.3, 125.5, 124.1, 123.7, 121.6, 120.2, 51.6, 20.2; HRMS (ESI): m/z [M + H]+ calcd
for C18H16NO2S: 310.0896; Found: 310.0904.
4.2 General procedure for ruthenium-catalyzed ortho-oxidative alkenylation of
2-arylthiazoles
4
in aqueous solution of anionic surfactant sodium
dodecylbenzenesulfonate (SDBS)
A suspension of 2-arylthiazoles 4 (0.3 mmol), acrylates 2 (0.6 mmol, 2.0 equiv),
[RuCl2(p-cymene)]2 (18.3 mg, 10 mol%), KPF6 (11.1 mg, 20 mol%), Cu(OAc)2·H2O
(119.7 mg, 2.0 equiv), and SDBS (41.7 mg, 40 mol%) in H2O (3.0 mL) was stirred at
o
80 C under air for 24 h. After that, the solution was extracted with EtOAc. The
combined organic phase was dried with MgSO4 and concentrated under reduced
pressure. The residue was purified by column chromatography on silica gel
(Petroleum ether/EtOAc: 10/1) to yield alkenlated product 5.
4.2.1 (E)-butyl 3-(3-methyl-2-(thiazol-2-yl)phenyl)acrylate 5a. Yellow oil (85%); Rf =
0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J =
3.3 Hz, 1H), 7.54 (t, J = 6.3 Hz, 2H), 7.39 (dd, J = 19.8, 11.9 Hz, 2H), 7.31 (d, J = 7.5
Hz, 1H), 6.30 (d, J = 15.9 Hz, 1H), 4.11 (t, J = 6.6 Hz, 2H), 2.19 (s, 3H), 1.61 (dt, J =
14.5, 6.7 Hz, 2H), 1.36 (dq, J = 14.6, 7.4 Hz, 2H), 0.92 (t, J = 7.4 Hz, 3H); 13C NMR
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(100 MHz, CDCl3) δ 166.6, 164.6, 143.1, 142.2, 138.6, 135.0, 133.9, 131.6, 129.6,
124.0, 121.0, 120.2, 64.3, 30.6, 20.2, 19.1, 13.7; HRMS (ESI): m/z [M + H]+ calcd for
C17H19NO2S: 302.1209; found: 302.1210.
4.2.2 (E)-butyl 3-(3-methoxy-2-(thiazol-2-yl)phenyl)acrylate 5b. Yellow oil (83%); Rf
= 0.2 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J
= 3.3 Hz, 1H), 7.77 (d, J = 15.9 Hz, 1H), 7.52 (d, J = 3.3 Hz, 1H), 7.42 (t, J = 8.1 Hz,
1H), 7.31 (d, J = 7.8 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H), 6.34 (d, J = 15.9 Hz, 1H), 4.15
(t, J = 6.6 Hz, 2H), 3.85 (s, 3H), 1.65 – 1.59 (m, 3H), 1.39 (dd, J = 15.0, 7.5 Hz, 2H),
13
0.94 (t, J = 7.4 Hz, 3H); C NMR (100 MHz, CDCl3) δ 166.8, 161.3, 157.6, 143.5,
142.5, 136.3, 130.4, 122.9, 120.9, 120.2, 119.6, 112.1, 64.3, 56.0, 30.7, 19.2, 13.7;
HRMS (ESI): m/z [M + H]+ calcd for C17H19NO3S: 318.1158; found: 318.1160.
4.2.3 (E)-butyl 3-(4-methyl-2-(thiazol-2-yl)phenyl)acrylate 5c. Yellow oil (92%); Rf =
0.3 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J =
15.9 Hz, 1H), 7.95 (d, J = 3.3 Hz, 1H), 7.66 – 7.52 (m, 2H), 7.44 (d, J = 3.3 Hz, 1H),
7.32 – 7.15 (m, 1H), 6.40 (d, J = 15.9 Hz, 1H), 4.19 (t, J = 6.6 Hz, 2H), 2.42 (s, 3H),
1.67 (dt, J = 14.6, 6.7 Hz, 2H), 1.43 (dq, J = 14.6, 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz,
13
3H); C NMR (100 MHz, CDCl3) δ 167.0, 166.4, 143.7, 143.2, 140.2, 133.3, 131.1,
130.8, 130.6, 127.6, 120.4, 119.7, 64.3, 30.7, 21.2, 19.2, 13.7; HRMS (ESI): m/z [M +
H]+ calcd for C17H19NO2S: 302.1209; found: 302.1211.
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4.2.4 (E)-butyl 3-(5-methyl-2-(thiazol-2-yl)phenyl)acrylate 5d(mono). Colorless oil
(52%); Rf = 0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ
8.30 (d, J = 15.9 Hz, 1H), 7.94 (d, J = 3.3 Hz, 1H), 7.64 (d, J = 7.9 Hz, 1H), 7.51 (s,
1H), 7.41 (d, J = 3.3 Hz, 1H), 7.28 (s, 1H), 6.42 (d, J = 15.9 Hz, 1H), 4.20 (t, J = 6.6
Hz, 2H), 2.42 (s, 3H), 1.73 – 1.64 (m, 2H), 1.44 (dq, J = 14.6, 7.4 Hz, 3H), 0.96 (t, J =
7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 166.9, 166.5, 143.7, 143.6, 139.8, 133.4,
130.7, 130.6, 130.4, 128.3, 120.4, 120.1, 64.4, 30.7, 21.3, 19.2, 13.7; HRMS (ESI):
m/z [M + H]+ calcd for C17H19NO2S: 302.1209; found: 302.1212.
4.2.5 (2E,2'E)-dibutyl 3,3'-(5-methyl-2-(thiazol-2-yl)-1,3-phenylene)diacrylate 5d(di).
Yellow oil (42%); Rf = 0.2 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz,
CDCl3) δ 8.00 (d, J = 3.3 Hz, 1H), 7.57 (d, J = 3.3 Hz, 1H), 7.54 (s, 2H), 7.47 (d, J =
15.9 Hz, 2H), 6.34 (d, J = 15.9 Hz, 2H), 4.13 (t, J = 6.6 Hz, 4H), 2.46 (s, 3H), 1.64 –
1.57 (m, 4H), 1.36 (dt, J = 14.6, 7.4 Hz, 4H), 0.93 (t, J = 7.4 Hz, 6H); 13C NMR (100
MHz, CDCl3) δ 166.4, 162.9, 143.4, 141.8, 140.0, 135.5, 131.3, 128.6, 121.8, 120.9,
64.4, 30.6, 21.4, 19.1, 13.7; HRMS (ESI): m/z [M + H]+ calcd for C24H29NO4S:
428.1890; found: 428.1889.
4.2.6 (E)-butyl 3-(2-(thiazol-2-yl)phenyl)acrylate 5e(mono). Yellow oil (32%); Rf =
0.4 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J =
15.9 Hz, 1H), 7.96 (d, J = 3.3 Hz, 1H), 7.73 (ddd, J = 16.6, 5.5, 3.4 Hz, 2H), 7.47
(ddd, J = 10.8, 8.2, 4.9 Hz, 3H), 6.43 (d, J = 15.9 Hz, 1H), 4.20 (t, J = 6.6 Hz, 2H),
27

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13
1.72 – 1.63 (m, 2H), 1.48 – 1.38 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H); C NMR (100
MHz, CDCl3) δ 166.8, 166.4, 143.8, 143.4, 133.6, 133.3, 130.5, 129.8, 129.7, 127.7,
120.7, 120.5, 64.4, 30.7, 19.2, 13.7; HRMS (ESI): m/z [M + H]+ calcd for
C16H17NO2S: 288.1053; found: 288.1050.
4.2.7 (2E,2'E)-dibutyl 3,3'-(2-(thiazol-2-yl)-1,3-phenylene)diacrylate 5e(di). Yellow
oil (56%); Rf = 0.2 (petroleum ether/ethyl acetate = 10:1); 1H NMR (400 MHz, CDCl3)
δ 8.02 (d, J = 3.3 Hz, 1H), 7.73 (d, J = 7.9 Hz, 2H), 7.60 (d, J = 3.3 Hz, 1H), 7.50 (dd,
J = 19.7, 11.9 Hz, 3H), 6.35 (d, J = 15.9 Hz, 2H), 4.13 (t, J = 6.6 Hz, 4H), 1.62 (dt, J
13
= 14.5, 6.6 Hz, 4H), 1.44 – 1.30 (m, 4H), 0.93 (t, J = 7.4 Hz, 6H); C NMR (100
MHz, CDCl3) δ 166.3, 162.6, 143.4, 141.5, 135.7, 133.9, 130.0, 127.9, 121.9, 121.2,
64.4, 30.6, 19.1, 13.6; HRMS (ESI): m/z [M + H]+ calcd for C23H27NO4S: 414.1734;
found: 414.1737.
Acknowledgements
Financial support from the National Natural Science Foundation of China (21262016,
21662017) and Natural Science Foundation of Jiangxi Province of China
(20133ACB20008，2144BAB2150015) is gratefully acknowledged.
Notes and references
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F.; Leong, C. O. Mol. Cancer Ther. 2011, 10, 1982; (c) Rajashekhar, H.; Ramesh, D.;
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Chandarashekhar, C.; Mahadevan, K. M.; Vaidya, V. P. Indian J. Heterocycl. Chem.
2009, 18, 205; (d) Aiello, S.; Wells, G.; Stone, E. L.; Kadri, H.; Bazzi, R.; Bell, D. R.;
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Hutchinson, I.; Chua, M. S.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.; Westwell,
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Amis, L. H.; Senthil, M. Eileen Brantley AACR 106th Annual Meeting 2015. April
18-22, 2015; (b) Coliva, A.; Monterisi, C.; Apollaro, A.; Gatti, D.; Penso, M.;
Gianolli, L.; Perani, D.; Gilardi, M. C.; Carpinelli, A. Appl. Radiat. Isotopes 2015,
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