Design and synthesis of 2-acylbenzothiazoles via in situ cross-trapping strategy from benzothiazoles with aryl ketones

Article abstract of DOI:10.1021/jo302754c

An I₂/KOH synergistically promoted direct ring-opening aroylation of benzothiazoles with aryl ketones has been discovered. Aryl ketones were seen to act as carbonyl sources to construct 2-acylbenzothiazoles. This reaction could provide an example for the convergent integration of self-labor domino sequences based on an in situ cross-trapping strategy.

Full text of DOI:10.1021/jo302754c

Note
pubs.acs.org/joc
Design and Synthesis of 2‑Acylbenzothiazoles via In Situ Cross-
Trapping Strategy from Benzothiazoles with Aryl Ketones
Qinghe Gao, Xia Wu, Fengcheng Jia, Meicai Liu, Yanping Zhu, Qun Cai, and Anxin Wu*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University,
Wuhan 430079, P. R. China
S
* Supporting Information
ABSTRACT: An I2/KOH synergistically promoted direct
ring-opening aroylation of benzothiazoles with aryl ketones
has been discovered. Aryl ketones were seen to act as carbonyl
sources to construct 2-acylbenzothiazoles. This reaction could
provide an example for the convergent integration of self-labor
domino sequences based on an in situ cross-trapping strategy.
he development of synthetic strategies for the effective
synthesis of complex products from simple substrates is an
Scheme 2. Logical Design and Synthesis of 2-
Acylbenzothiazoles
T
ongoing interest in organic chemistry. Accordingly, the in situ
trapping of unstable intermediates via domino reactions has
already been successfully developed.1 Recently, we reported an
efficient strategy for the in situ trapping of metastable α-
ketoaldehyde intermediates, providing a new method for direct
synthesis of pharmacologically interesting heterocycles.2
Inspired by the in situ trapping of one type of intermediates
(Scheme 1a), we envisioned that substrates could be
Scheme 1. In Situ Trapping Strategies
α-ketoaldehyde intermediate could cross-trap another in situ
formed 2-aminobenzenethiol via condensation, Michael
addition, and oxidative dehydrogenation sequences to construct
2-acylbenzothiazole (Scheme 2d).
concurrently involved in two or more different domino
sequences, with the in situ trapping of respectively generated
intermediates converging on the desired product (Scheme 1b).
This could provide a more efficient tool for constructing
complex molecules from diverse simple substrates. To
demonstrate the power and potential of the in situ cross-
trapping strategy, we herein present a convenient and efficient
method for the direct aroylation of benzothiazoles with aryl
ketones.
2-Acylbenzothiazoles have attracted much attention due to
their diverse biological activities5 and have also been used to
study the regioselectivity in Grignard reagent reactions.6
However, only a few procedures have been developed to
access 2-acylbenzothiazoles due to the difficulty in introducing
an acyl group at the 2-position of benzothiazoles.7 Therefore,
the development of a direct aroylation of benzothiazoles
protocol to access 2-acylbenzothiazoles derivatives has aroused
great interest.8 Meanwhile, direct aroylation of the aromatic
rings remains an important transformation in organic synthesis.
They are usually synthesized by the classical Friedel−Crafts
In our previous studies,2 methyl ketones were seen to be
transformed in situ to α-ketoaldehydes via a domino
iodination−Kornblum oxidation reaction (Scheme 2a). Accord-
ing to previous literatures, benzothiazole could be converted to
2-aminobenzenethiol via a domino deprotonation−hydroxyza-
tion reaction,3 which allowed a further reaction with α-
ketoaldehyde to afford 2-acylbenzothiazoles4 (Scheme 2b and
c). We therefore suppose that the in situ generated metastable
Received: December 27, 2012
Published: February 20, 2013
© 2013 American Chemical Society
2792
dx.doi.org/10.1021/jo302754c | J. Org. Chem. 2013, 78, 2792−2797

The Journal of Organic Chemistry
Note
a
Table 1. Optimization of the Reaction Conditions
b
entry
I2 (equiv)
base
solvent
DMSO
temp (°C)
yield (%)
1
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.2
1.0
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
80
8
47
69
83
0
2
DMSO/H2O(1:1)
DMSO/H2O(2:1)
DMSO/H2O(3:1)
H2O
3
4
5
6
K3PO4·3H2O
K2CO3
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
DMSO/H2O(3:1)
52
28
85
88
12
50
48
0
7
8
t-BuOK
9
KOH
10
11
12
13
14
15
16
17
Cs2CO3
NaOH
LiOH·H2O
NaHCO3
0
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
81
48
0
c
18
d
1.5
1.5
1.5
1.5
1.5
75
72
15
77
85
19
20
21
22
90
DMSO/H2O(3:1)
110
a
b
c
d
Reaction conditions: 1a (1.0 mmol), 2a (1.5 mmol), base (1.0 mmol), solvent (4 mL). Isolated yields. 2a (1.2 mmol). 2a (1.0 mmol).
a
Scheme 3. Scope of Methyl Ketones
a
Reaction conditions: 1 (1.0 mmol), 2a (1.5 mmol), I2 (1.5 mmol), and KOH (1.0 mmol) in DMSO/H2O = 3:1 mL at 100 °C. Isolated yield.
2793
dx.doi.org/10.1021/jo302754c | J. Org. Chem. 2013, 78, 2792−2797

The Journal of Organic Chemistry
Note
a
Scheme 4. Scope of Methyl Ketones and Benzothiazoles
a
Isolated yield
Scheme 5. Possible Mechanism
acylation.9 Alternatively, the direct aroylation of aryl C−H
bonds with carbonyl sources, such as carbon monoxide,10
aldehydes,11 alcohols,12 α-ketone acids,13 α-diketones,14 and
alkylbenzene,15 could potentially complement Friedel−Crafts
acylation. However, heteroaryl compounds have proven to be
much less applicable to these methods.8,16 In this paper, an I2/
KOH synergistically promoted aroylation of benzothiazoles
with aryl ketones is described.
We initiated the present study with acetophenone (1a) and
benzothiazole (2a) as model substrates. It was found that the
reaction led to the desired product 2-acylbenzothiazole (3aa) in
a very low yield of 8% (Table 1, entry 1). To our surprise, the
reaction could perform in moderate yield in the presence of
H2O (Table 1, entry 2). When the ratio of DMSO to H2O was
changed from 1:1 to 3:1, the yield increased to 83% (Table 1,
entry 4). Other bases were also tested, which demonstrated that
KOH was the best choice (Table 1, entries 6−13). However,
aroylation of benzoxazole was not observed in the absence of
either base or iodine, indicating that an I2/KOH combination is
crucial for the reaction (Table 1, entries 14 and 17).
in moderate to excellent yields (62−95%; 3aa−3ia). Much to
our satisfaction, the conditions were mild enough to be
compatible with halogenated (4-F, 4-Cl, 4-Br) and hydroxy-
lated substrates (67−73%; 3ja−3ma). Notably, 2-naphthyl
methyl ketone and 1-naphthyl methyl ketone also gave their
corresponding products 3na and 3oa in 78% and 80% yields,
respectively. Furthermore, heteroaryl ketones, including
benzofuryl, furanyl, thienyl, and morpholinyl, were also found
to be adept in efficiently furnishing the desired products in
moderate to excellent yields (62−83%; 3pa−3ta).
Subsequently, the scope was also extended to some
substituted benzothiazoles (Scheme 4). To our delight,
benzothiazoles with electron-rich and electron-deficient sub-
stituents at the phenyl ring worked well under the optimized
reaction conditions, affording the corresponding products 3ab−
3nc in 70−82% yields. On the other hand, 6-bromobenzothia-
zole (2d) was also tolerant to the reaction. The corresponding
products 3ad−3jd were thus obtained in 59−79% yields.
Unfortunately, benzoxazole and benzimidazole could not be
applied to this transformation.17
After achieving the optimized reaction conditions, the scope
of aryl methyl ketones was explored (Scheme 3). Aryl methyl
ketones bearing electron-neutral (4-H, 4-Me), electron-rich (4-
OMe, 4-OEt, 2,4-OMe2, 3,4-OCH2O, 3,4-OCH2CH2O), and
electron-deficient (4-NO2, 4-Ph) groups all participated in this
reaction smoothly to afford the expected 2-acylbenzothiazoles
On the basis of the control experiments (Supporting
Information, Figure S1), a plausible mechanism for the reaction
was proposed (Scheme 5). Initially, 1a was converted to α-iodo
acetophenone in the presence of I2. Subsequently, further
oxidation of 1aa by DMSO took place to 1ab and 1ac. At the
same time, the ring-opened intermediate B was generated by
2794
dx.doi.org/10.1021/jo302754c | J. Org. Chem. 2013, 78, 2792−2797

The Journal of Organic Chemistry
Note
Benzo[d][1,3]dioxol-5-yl(benzo[d]thiazol-2-yl)methanone (3fa).
Yellow solid; 260.4 mg (yield 92%); mp 134−138 °C; IR (KBr)
1626, 1596, 1486, 1273 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.43−8.38 (m, 1H), 8.23 (d, J = 7.8 Hz, 1H), 8.06 (br, 1H), 8.01 (d, J
= 8.4 Hz, 1H), 7.61−7.52 (m, 2H), 6.97 (d, J = 8.4 Hz, 1H), 6.10 (s,
2H); 13C NMR (150 MHz, CDCl3) δ (ppm) 182.9, 167.6, 153.8,
152.7, 148.0, 136.9, 129.3, 128.7, 127.4, 126.8, 125.6, 122.1, 110.7,
108.2, 102.0; HRMS (ESI) m/z [M + H]+ calcd for C15H10NO3S
284.0376, found 284.0381.
deprotonation of 2a under the assistance of KOH. The
intermediate C that was formed through hydroxyzation of B3,18
in situ trapped 1ab to give intermediate D. Finally, D via
Michael addition and oxidative dehydrogenation sequences to
furnished the desired product 3aa in the presence of iodide.4a
In summary, we have developed an I2/KOH synergistically
promoted aroylation of benzothiazoles using aryl ketones as
carbonyl sources. The protocol could provide an efficient
method to synthesize 2-acylbenzathiazoles through an in situ
cross-trapping strategy. This method could complement the
existing methods of aroylation of aromatic rings.
3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-6-phenylpyridazine
(3ga).4a Yellow solid; 282.2 (yield 95%); mp 140−142 °C; IR (KBr)
1629, 1593, 1494, 1302 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.27−8.21 (m, 2H), 8.18 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H),
7.60−7.49 (m, 2H), 7.01 (d, J = 8.4 Hz, 1H), 4.36 (s, 2H), 4.32 (s,
2H); 13C NMR (150 MHz, CDCl3) δ (ppm) 183.2, 167.6, 153.8,
149.1, 143.2, 136.8, 128.3, 127.4, 126.8, 125.7, 125.6, 122.1, 120.9,
117.3, 64.8, 64.0; HRMS (APCI) m/z [M + H]+ calcd for
C16H12NO3S 298.0532, found 298.0531.
EXPERIMENTAL SECTION
■
General Information. IR spectra were recorded as KBr pellets
with absorption in cm−1. 1H NMR and 13C NMR spectra were
recorded in CDCl3 or DMSO-d6. HRMS were obtained on a 7.0T
FTMS equipped with ESI or APCI.
Benzo[d]thiazol-2-yl(4-nitrophenyl)methanone (3ha).7a Yellow
solid; 176.1 mg (yield 62%); mp 174−277 °C; IR (KBr) 1643,
General Procedure for the Synthesis of 3 (3aa as Example).
A mixture of acetophenone 1a (1.0 mmol), benzothiazole 2a (1.5
mmol), I2 (1.5 mmol), and KOH (1.0 mmol) in DMSO/H2O = 3:1
mL was stirred at 100 °C. After disappearance of the reactant
(monitored by TLC), 50 mL of water was added to the mixture, which
was then extracted with EtOAc 3 times. The extract was washed with
Na2S2O3 solution, dried over anhydrous Na2SO4, and evaporated. The
residue was purified by column chromatography to afford 3aa.
Benzo[d]thiazol-2-yl(phenyl)methanone (3aa).4c Yellow solid;
210.3 mg (yield 88%); mp 97−99 °C; IR (KBr) 1667, 1596, 1485,
1272 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm) 8.56 (d, J = 7.8 Hz,
2H), 8.24 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.67 (t, J = 7.2
Hz, 1H), 7.60−7.53 (m, 4H); 13C NMR (150 MHz, CDCl3) δ (ppm)
185.3, 167.1, 153.8, 136.9, 134.9, 133.9, 131.2, 128.5, 127.6, 126.9,
125.7, 122.1; HRMS (APCI) m/z [M + H]+ calcd for C14H10NOS
240.0478, found 240.0473.
1
1597, 1482, 1293 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.74
(d, J = 9.0 Hz, 2H), 8.40 (d, J = 9.0 Hz, 2H), 8.26 (d, J = 7.8 Hz, 1H),
8.05 (d, J = 7.8 Hz, 1H), 7.65−7.58 (m, 2H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 183.8, 165.8, 153.7, 150.5, 139.7, 137.2, 132.3, 128.3,
127.3, 125.9, 123.5, 122.3; HRMS (APCI) m/z [M + H]+ calcd for
C14H9N2O3S 285.0328, found 285.0328.
[1,1′-Biphenyl]-4-yl(benzo[d]thiazol-2-yl)methanone (3ia).4a Yel-
low solid; 261.4 mg (yield 83%); mp 104−107 °C; IR (KBr) 1636,
1
1600, 1484, 1294 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.64
(d, J = 7.8 Hz, 2H), 8.25 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H),
7.77 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 7.8 Hz, 2H), 7.60−7.51 (m, 2H),
7.50−7.44 (m, 2H), 7.42−7.39 (m, 1H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 184.7, 167.2, 153.8, 146.5, 139.8, 136.9, 133.6, 131.8,
128.9, 128.3, 127.6, 127.3, 127.1, 126.9, 125.7, 122.1; HRMS (APCI)
m/z [M + H]+ calcd for C20H14NOS 316.0791, found 316.0790.
Benzo[d]thiazol-2-yl(4-fluorophenyl)methanone (3ja).4b Yellow
solid; 187.6 mg (yield 73%); mp 100−102 °C; IR (KBr) 1641, 1594,
Benzo[d]thiazol-2-yl(p-tolyl)methanone (3ba).4c Yellow solid;
210 mg (yield 83%); mp 95−97 °C; IR (KBr) 1640, 1604, 1482,
1290 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm) 8.47 (d, J = 7.8 Hz,
2H), 8.23 (d, J = 7.8 Hz, 1H), 7.80 (d, J = 8.4 Hz, 1H), 7.59−7.51 (m,
2H), 7.35 (d, J = 7.8 Hz, 2H), 2.46 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 184.9, 167.4, 153.8, 145.0, 136.9, 132.3, 131.4, 129.2,
127.4, 126.8, 125.6, 122.1, 21.8; HRMS (APCI) m/z [M + H]+ calcd
for C15H12NOS 254.0634, found 254.0630.
1
1485, 1292 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.69−8.64
(m, 2H), 8.23 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.61−7.52
(m, 2H), 7.25−7.21 (m, 2H); 13C NMR (150 MHz, CDCl3) δ (ppm)
183.5, 167.2, 167.0, 165.5, 153.8, 136.9, 134.2, 134.1, 131.2, 127.7,
127.0, 125.6, 122.1, 115.8, 115.6; HRMS (APCI) m/z [M + H]+ calcd
for C14H9FNOS 258.0383, found 258.0385.
Benzo[d]thiazol-2-yl(4-chlorophenyl)methanone (3ka).4c White
solid; 182.9 mg (yield 67%); mp 99−102 °C; IR (KBr) 1639, 1586,
1480, 1293 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm) 8.56 (d, J =
8.4 Hz, 2H), 8.24 (d, J = 7.8 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.63−
7.52 (m, 4H); 13C NMR (150 MHz, CDCl3) δ (ppm) 184.0, 166.8,
153.8, 140.6, 137.0, 133.2, 132.7, 128.9, 127.8, 127.0, 125.7, 122.2;
HRMS (APCI) m/z [M + H]+ calcd for C14H9ClNOS 274.0088,
found 274.00863.
Benzo[d]thiazol-2-yl(4-methoxyphenyl)methanone (3ca).7a
White solid; 242.1 mg (yield 90%); mp 118−121 °C; IR (KBr)
1628, 1602, 1492, 1302 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.64 (d, J = 9.0 Hz, 2H), 8.22 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz,
1H), 7.59−7.50 (m, 2H), 7.03 (d, J = 9.0 Hz, 2H), 3.91 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ (ppm) 183.3, 167.8, 164.3, 153.8, 136.8,
133.8, 127.7, 127.3, 126.7, 125.5, 122.1, 113.8, 55.5; HRMS (APCI)
m/z [M + H]+ calcd for C15H12NO2S 270.0583, found 270.0581.
Benzo[d]thiazol-2-yl(4-ethoxyphenyl)methanone (3da). Yellow
solid; 246.2 mg (yield 87%); mp 112−115 °C; IR (KBr) 1631,
Benzo[d]thiazol-2-yl(4-bromophenyl)methanone (3la).4c Yellow
solid; 228.2 mg (yield 72%); mp 121−123 °C; IR (KBr) 1641, 1581,
1477, 1291 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm) 8.46 (d, J =
8.4 Hz, 2H), 8.22 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.69
(d, J = 8.4 Hz, 2H), 7.60−7.52 (m, 2H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 184.1, 166.7, 153.7, 137.0, 133.6, 132.7, 131.8, 129.5,
127.8, 127.0, 125.7, 122.2; HRMS (APCI) m/z [M + H]+ calcd for
C14H9BrNOS 317.9583, found 317.9581.
1
1604, 1493, 1298 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.64
(d, J = 9.0 Hz, 2H), 8.24 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H),
7.60−7.51 (m, 2H), 7.03 (d, J = 9.0 Hz, 2H), 4.16 (q, J = 7.2 Hz, 2H),
1.48 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 183.2,
167.9, 163.8, 153.8, 136.8, 133.8, 127.5, 127.3, 126.7, 125.5, 122.0,
114.2, 63.80, 14.61; HRMS (ESI) m/z [M + H]+ calcd for
C16H14NO2S 284.0740, found 284.0742.
Benzo[d]thiazol-2-yl(4-hydroxyphenyl)methanone (3ma).4a Yel-
low solid; 176 mg (yield 69%); mp 179−182 °C; IR (KBr) 1628,
Benzo[d]thiazol-2-yl(2,4-dimethoxyphenyl)methanone (3ea).4a
Yellow solid; 203.3 mg (yield 68%); mp 122−125 °C; IR (KBr)
1646, 1604, 1458, 1271 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.15 (d, J = 7.8 Hz, 1H), 8.01−7.96 (m, 2H), 7.55−7.47 (m, 2H),
6.62−6.58 (m, 1H), 6.56−6.54 (m, 1H), 3.88 (s, 3H), 3.80 (s, 3H);
13C NMR (150 MHz, CDCl3) δ (ppm) 185.5, 168.3, 164.7, 161.3,
153.5, 136.9, 134.3, 127.1, 126.6, 125.3, 122.1, 118.5, 104.6, 99.1, 55.8,
55.5; HRMS (APCI) m/z [M + H]+ calcd for C16H14NO3S 300.0689,
found 300.0685.
1
1597, 1487, 1239 cm−1; H NMR (600 MHz, DMSO-d6) δ (ppm)
10.77, (s, 1H), 8.48 (d, J = 9.0 Hz, 2H), 8.27−8.20 (m, 2H), 7.66−
7.58 (m, 2H), 6.98 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, DMSO-
d6) δ (ppm) 182.2, 167.8, 163.5, 153.3, 136.0, 133.8, 127.7, 127.2,
125.5, 125.1, 122.7, 115.6; HRMS (APCI) m/z [M + H]+ calcd for
C14H10NO2S 256.0427, found 256.0423.
Benzo[d]thiazol-2-yl(naphthalen-2-yl)methanone (3na).4a Yel-
low solid; 225.4 mg (yield 78%); mp 164−166 °C; IR (KBr) 1632,
1
1618, 1485, 1291 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 9.34
2795
dx.doi.org/10.1021/jo302754c | J. Org. Chem. 2013, 78, 2792−2797

The Journal of Organic Chemistry
Note
(s, 1H), 8.43 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz, 1H), 8.08 (d, J =
8.4 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 9.0 Hz, 1H), 7.91
(d, J = 8.4 Hz, 1H), 7.66−7.54 (m, 4H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 185.1, 167.3, 153.9, 137.0, 135.9, 134.3, 132.4, 132.1,
130.2, 129.0, 128.3, 127.8, 127.6, 126.9, 126.7, 125.8, 125.7, 122.2;
HRMS (APCI) m/z [M + H]+ calcd for C18H12NOS 290.0634, found
290.0633.
8.44 (d, J = 6.6 Hz, 2H), 8.09 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 6.6 Hz,
2H), 7.40 (s, 1H), 7.19 (d, J = 7.8 Hz, 1H), 3.93 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ (ppm) 184.0, 159.9, 148.4, 139.2, 133.8, 133.0,
132.6, 131.7, 129.2, 126.5, 117.8, 109.9, 55.9; HRMS (ESI) m/z [M +
H]+ calcd for C15H11BrNO2S 347.9688, found 347.9694.
(6-Methoxybenzo[d]thiazol-2-yl)(naphthalen-2-yl)methanone
(3nb). Yellow solid; 226.5 mg (yield 71%); mp 179−182 °C; IR (KBr)
1615, 1602, 1490, 1255 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
9.31 (s, 1H), 8.42 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 9.0 Hz, 1H), 8.07
(d, J = 7.8 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H),
7.66−7.55 (m, 2H), 7.43 (s, 1H), 7.20 (d, J = 9.0 Hz, 1H), 3.93 (s,
3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 184.8, 164.7, 159.7,
148.5, 139.1, 135.8, 134.0, 132.4(3), 132.3(7), 130.2, 128.9, 128.2,
127.7, 126.6, 126.5, 125.8, 117.6, 103.4, 55.8; HRMS (ESI) m/z [M +
H]+ calcd for C19H14NO2S 320.0740, found 320.0742.
Benzo[d]thiazol-2-yl(naphthalen-1-yl)methanone (3oa).4a Yel-
low solid; 231.2 mg (yield 80%); mp 141−143 °C; IR (KBr) 1653,
1
1593, 1481, 1254 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.52
(d, J = 8.4 Hz, 1H), 8.35 (d, J = 7.2 Hz, 1H), 8.20−8.17 (m, 1H), 8.10
(d, J = 8.4 Hz, 1H), 8.05−8.02 (m, 1H), 7.93 (d, J = 7.8 Hz, 1H),
7.63−7.52 (m, 5H); 13C NMR (150 MHz, CDCl3) δ (ppm) 188.3,
168.0, 153.7, 137.3, 133.9, 133.6, 132.2, 131.9, 131.1, 128.6, 128.0,
127.7, 127.0, 126.6, 125.8, 125.4, 124.3, 122.2; HRMS (APCI) m/z [M
+ H]+ calcd for C18H12NOS 290.0634, found 290.0633.
Naphthalen-2-yl(6-nitrobenzo[d]thiazol-2-yl)methanone (3nc).
Yellow solid; 273.9 mg (yield 82%); mp 192−195 °C; IR (KBr)
1700, 1646, 1342, 1233 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
9.34 (s, 1H), 8.91 (s, 1H), 8.47−8.33 (m, 3H), 8.06 (d, J = 7.2 Hz,
1H), 7.96 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 6.6 Hz, 1H), 7.70−7.63 (m,
1H), 7.62−7.55 (m, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm)
183.8, 172.7, 157.1, 146.4, 137.0, 136.1, 134.7, 132.3, 131.3, 130.3,
129.5, 128.6, 127.8, 127.0, 126.1, 125.5, 121.9, 118.7; HRMS (ESI) m/
z [M + H]+ calcd for C18H11N2O3S 335.0485, found 335.0485.
(6-Bromobenzo[d]thiazol-2-yl)(phenyl)methanone (3ad).7d Yel-
low solid; 187 mg (yield 59%); mp 117−120 °C; IR (KBr) 1641,
Benzo[d]thiazol-2-yl(benzofuran-2-yl)methanone (3pa).4a Yel-
low solid; 189.7 mg (yield 68%); mp 123−125 °C; IR (KBr) 1637,
1
1542, 1488, 1215 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.76
(s, 1H), 8.26 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.82 (d, J =
7.2 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.60 (t, J = 7.2 Hz, 1H), 7.56−
7.50 (m, 2H), 7.44 (m, 1H); 13C NMR (150 MHz, CDCl3) δ (ppm)
173.8, 165.8, 156.3, 153.7, 149.6, 136.9, 129.2, 127.7, 127.3, 127.1,
125.5, 124.1, 124.0, 122.2, 121.0, 112.6; HRMS (APCI) m/z [M + H]+
calcd for C16H10NO2S 280.0427, found 280.0425.
Benzo[d]thiazol-2-yl(furan-2-yl)methanone (3qa).4a Yellow solid;
167.2 mg (yield 73%); mp 149−151 °C; IR (KBr) 1640, 1554, 1493,
1230 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm) 8.38 (d, J = 3.6 Hz,
1H), 8.23 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.84 (s, 1H),
7.62−7.53 (m, 2H), 7.68−7.67 (m, 1H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 172.0, 166.0, 153.7, 149.8, 148.9, 136.8, 127.5, 127.0,
125.5, 125.0, 122.2, 112.9; HRMS (APCI) m/z [M + H]+ calcd for
C12H8NO2S 230.0270, found 230.0265.
1
1491, 1478, 1266 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.54
(d, J = 7.8 Hz, 2H), 8.15 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.71−7.64
(m, 2H), 7.59−7.53 (m, 2H); 13C NMR (100 MHz, CDCl3) δ (ppm)
184.9, 167.6, 152.6, 138.5, 134.7, 134.1, 131.2, 130.6, 128.5, 126.7,
124.7, 121.9; HRMS (ESI) m/z [M + H]+ calcd for C14H9BrNOS
317.9583, found 317.9586.
(6-Bromobenzo[d]thiazol-2-yl)(4-methoxyphenyl)methanone (3
Benzo[d]thiazol-2-yl(thiophen-2-yl)methanone (3ra).4a Yellow
solid; 151.9 mg (yield 62%); mp 104−106 °C; IR (KBr) 1618,
cd). Yellow solid; 274.1 mg (yield 79%); mp 162−165 °C; IR
1
(KBr) 1636, 1601, 1487, 1262 cm−1; H NMR (600 MHz, CDCl3) δ
(ppm) 8.64 (d, J = 7.8 Hz, 2H), 8.16 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H),
7.68 (d, J = 8.4 Hz, 1H), 7.04 (d, J = 7.8 Hz, 2H), 3.93 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ (ppm) 182.9, 164.5, 152.7, 138.4, 133.8,
132.4, 130.5, 127.5, 126.6, 124.7, 121.6, 113.9, 55.6; HRMS (ESI) m/z
[M + H]+ calcd for C15H11BrNO2S 347.9688, found 347.9696.
(6-Bromobenzo[d]thiazol-2-yl)(4-bromophenyl)methanone
(3jd). Yellow solid; 248.2 mg (yield 63%); mp 129−133 °C; IR (KBr)
1643, 1584, 1477, 1265 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.46 (d, J = 8.4 Hz, 2H), 8.16 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.73−
7.67 (m, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 183.7, 167.2,
152.5, 138.5, 133.3, 132.7, 131.9, 130.7, 129.7, 126.7, 124.7, 122.1;
HRMS (ESI) m/z [M + H]+ calcd for C14H8Br2NOS 395.8688, found
395.8681.
1
1459, 1409, 1227 cm−1; H NMR (600 MHz, CDCl3) δ (ppm) 8.76
(d, J = 3.0 Hz, 1H), 8.24 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H),
7.84 (d, J = 4.2 Hz, 1H), 7.61−7.50 (m, 2H), 7.26 (s, 1H); 13C NMR
(150 MHz, CDCl3) δ (ppm) 176.9, 166.5, 153.6, 139.6, 137.4, 136.9,
136.8, 128.5, 127.5, 126.9, 125.5, 122.2; HRMS (APCI) m/z [M + H]+
calcd for C12H8NOS2 246.0042, found 246.0038.
Benzo[d]thiazol-2-yl(thiophen-3-yl)methanone (3sa).4a Yellow
solid; 169 mg (yield 69%); mp 100−102 °C; IR (KBr) 1630, 1511,
1491, 1269 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm) 9.30 (s, 1H),
8.23 (d, J = 7.8 Hz,1H), 8.03−7.97 (m, 2H), 7.62−7.51 (m, 2H),
7.42−7.38 (m, 1H); 13C NMR (150 MHz, CDCl3) δ (ppm) 178.3,
167.5, 153.8, 138.4, 138.0, 136.9, 128.8, 127.5, 126.9, 125.8, 125.5,
122.2; HRMS (APCI) m/z [M + H]+ calcd for C12H8NOS2 246.0042,
found 246.0037.
ASSOCIATED CONTENT
Benzo[d]thiazol-2-yl(4-morpholinophenyl)methanone (3ta).4a
Yellow solid; 268.9 mg (yield 83%); mp 150−152 °C; IR (KBr)
1603, 1490, 1437, 1244 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.61 (d, J = 9.0 Hz, 2H), 8.22 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz,
1H), 7.58−7.49 (m, 2H), 6.95 (d, J = 8.4 Hz, 2H), 3.87 (t, J = 9.6 Hz,
4H), 3.39 (t, J = 9.0 Hz, 4H); 13C NMR (150 MHz, CDCl3) δ (ppm)
182.6, 168.5, 154.7, 153.9, 136.7, 133.6, 127.1, 126.6, 125.3, 125.0,
122.1, 113.0, 66.5, 47.1; HRMS (APCI) m/z [M + H]+ calcd for
C18H17N2O2S 325.1005, found 325.1003.
■
S
* Supporting Information
1H and 13C NMR spectra of compounds 3. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: chwuax@mail.ccnu.edu.cn.
■
(6-Methoxybenzo[d]thiazol-2-yl)(phenyl)methanone (3ab).7d
Yellow solid; 209.8 mg (yield 78%); mp 170−173 °C; IR (KBr)
1637, 1608, 1495, 1258 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
8.53 (d, J = 7.2 Hz, 2H), 8.10 (d, J = 9.0 Hz, 1H), 7.66 (t, J = 7.2 Hz,
1H), 7.58−7.53 (m, 2H), 7.41 (s, 1H), 7.18 (d, J = 8.4 Hz, 1H), 3.92
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 185.1, 164.7, 159.7,
148.5, 139.0, 135.1, 133.6, 131.1, 128.4, 126.4, 117.6, 103.3, 55.80;
HRMS (ESI) m/z [M + H]+ calcd for C15H12NO2S 270.0583, found
270.0586.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by the National Natural Science
Foundation of China (Grants 21032001, 21272085).
■
REFERENCES
■
(1) For reviews on domino reactions, see: (a) Tietze, L. F.; Brasche,
G.; Gericke, K. Domino Reactions in Organic Synthesis; Wiley-VCH:
Weinheim, Germany, 2006. (b) Nicolaou, K. C.; Montagnon, T.;
(4-Bromophenyl)(6-methoxybenzo[d]thiazol-2-yl)methanone
(3jb). Yellow solid; 242.9 mg (yield 70%); mp 197−199 °C; IR (KBr)
1636, 1604, 1495, 1257 cm−1; 1H NMR (600 MHz, CDCl3) δ (ppm)
2796
dx.doi.org/10.1021/jo302754c | J. Org. Chem. 2013, 78, 2792−2797

The Journal of Organic Chemistry
Note
Snyder, S. A. Chem. Commun. 2003, 551. (c) Shindoh, N.; Takemoto,
Y.; Takasu, K. Chem.Eur. J. 2009, 15, 12168. (d) Wang, Y.; Zhang,
W. X.; Wang, Z. T.; Xi, Z. F. Angew. Chem., Int. Ed. 2011, 50, 8122.
(2) (a) Yang, Y.; Gao, M.; Zhang, D. X.; Wu, L. M.; Shu, W. M.; Wu,
A. X. Tetrahedron 2012, 68, 7338. (b) Yang, Y.; Gao, M.; Deng, C.;
Zhang, D. X.; Wu, L. M.; Shu, W. M.; Wu, A. X. Tetrahedron 2012, 68,
6257. (c) Gao, Q. H.; Fei, Z.; Zhu, Y. P.; Lian, M.; Jia, F. C.; Liu, M.
C.; She, N. F.; Wu, A. X. Tetrahedron 2013, 69, 22.
(3) (a) Yao, L. F.; Zhou, Q.; Han, W.; Wei, S. H. Eur. J. Org. Chem.
2012, 6856. (b) Zhang, W.; Zeng, Q. L.; Zhang, X. M.; Tian, Y. J.; Yue,
Y.; Guo, Y. J.; Wang, Z. H. J. Org. Chem. 2011, 76, 4741. (c) Liu, S. W.;
Chen, R.; Guo, X. Y.; Yang, H. Q.; Deng, G. J.; Li, C. J. Green Chem.
2012, 14, 1577. (d) Feng, Y. S.; Qi, H. X.; Wang, W. C.; Liang, Y. F.;
Xu, H. J. Tetrahedron Lett. 2012, 53, 2914.
(4) (a) Zhu, Y. P.; Lian, M.; Jia, F. C.; Liu, M. C.; Yuan, J. J.; Gao, Q.
H.; Wu, A. X. Chem. Commun. 2012, 48, 9086. (b) Zhu, Y. P.; Jia, F.
C.; Liu, M. C.; Wu, A. X. Org. Lett. 2012, 14, 4414. (c) Yang, X. L.; Xu,
C. M.; Lin, S. M.; Chen, J. X.; Ding, J. C.; Wu, H. Y.; Su, W. K. J. Braz.
Chem. Soc. 2010, 21, 37. (d) Shokrolahi, A.; Zali, A.; Mahdavi, M.
Phosphorus, Sulfur Silicon Relat. Elem. 2012, 187, 535.
(5) (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003,
103, 893. (b) Marsilje, T. H.; Hedrick, M. P.; Desharnais, J.; Tavassoli,
A.; Zhang, Y.; Wilson, I. A.; Benkovicd, S. J.; Boger, D. L. Bioorg. Med.
Chem. 2003, 11, 4487. (c) Tsutsumi, S.; Okonogi, T.; Shibahara, S.;
Ohuchi, S.; Hatsushiba, E.; Patchett, A. A.; Christensen, B. G. J. Med.
Chem. 1994, 37, 3492.
(6) Boga, C.; Stengel, R.; Abdayem, R.; Vecchio, E. D.; Forlani, L.;
Todesco, P. E. J. Org. Chem. 2004, 69, 8903.
(7) (a) Fan, X. S.; He, Y.; Zhang, X. Y.; Guo, S. H.; Wang, Y. Y.
Tetrahedron 2011, 67, 6369. (b) Fan, X. S.; He, Y.; Wang, Y. Y.; Xue,
Z. K.; Zhang, X. Y.; Wang, J. J. Tetrahedron Lett. 2011, 52, 899.
(c) Fan, X. S.; He, Y.; Guo, S. H.; Zhang, X. Y. Aust. J. Chem. 2011, 64,
1568. (d) Hyvl, J.; Srogl, J. Eur. J. Org. Chem. 2010, 2849. (e) Mu, X.
J.; Zou, J. P.; Zeng, R. S.; Wu, J. C. Tetrahedron Lett. 2005, 46, 4345.
(f) Liao, Y. F.; Qi, H. R.; Chen, S. P.; Jiang, P. C.; Zhou, W.; Deng, G.
J. Org. Lett. 2012, 14, 6004.
(8) Wu, X. F.; Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem.,
Int. Ed. 2010, 49, 7316.
(9) (a) Olah, G. A. Friedel-Crafts Chemistry; Wiley: New York, 1973.
(b) Sartori, G.; Maggi, R. Chem. Rev. 2006, 106, 1077.
(10) For selected examples, see: (a) Liu, Q.; Zhang, H.; Lei, A. W.
Angew. Chem., Int. Ed. 2011, 50, 10788. (b) Brennfuhrer, A.;
̈
Neumann, H.; Beller, M. ChemCatChem 2009, 1, 28.
(11) For selected examples, see: (a) Wu, Y.; Li, B. Z.; Mao, F.; Li, X.
S.; Kwong, F. Y. Org. Lett. 2011, 13, 3258. (b) Jia, X. F.; Zhang, S. H.;
Wang, W. H.; Luo, F.; Cheng, J. Org. Lett. 2009, 11, 3120. (c) Basle,
́
O.; Bidange, J.; Shuai, Q.; Li, C. J. Adv. Synth. Catal. 2010, 352, 1145.
(d) Zhang, Q.; Li, C.; Yang, F.; Li, J. Y.; Wu, Y. J. Tetrahedron 2013,
69, 320. (e) Hu, J.; Adogla, E. A.; Ju, Y.; Fan, D. P.; Wang, Q. Chem.
Commun. 2012, 48, 11256.
́
(12) (a) Xiao, F. H.; Shuai, Q.; Zhao, F.; Basle, O.; Deng, G. J.; Li, C.
J. Org. Lett. 2011, 13, 1614. (b) Yuan, Y.; Chen, D. T.; Wang, X. W.
Adv. Synth. Catal. 2011, 353, 3373.
(13) (a) Li, M. Z.; Ge, H. B. Org. Lett. 2010, 12, 3464. (b) Fang, P.;
Li, M. Z.; Ge, H. B. J. Am. Chem. Soc. 2010, 132, 11898. (c) Wang, H.;
Guo, L. N.; Duan, X. H. Org. Lett. 2012, 14, 4358. (d) Kim, M. Y.;
Park, J.; Sharma, S.; Kim, A.; Park, E.; Kwak, J. H.; Jung, Y. H.; Kim, I.
S. Chem. Commun. 2013, 49, 925.
(14) Zhou, W.; Li, H. J.; Wang, L. Org. Lett. 2012, 14, 4594.
(15) (a) Guin, S.; Rout, S. K.; Banerjee, A.; Nandi, S.; Patel, B. K.
Org. Lett. 2012, 14, 5294. (b) Wu, Y.; Choy, P. Y.; Mao, F.; Kwong, F.
Y. Chem. Commun. 2013, 49, 689. (c) Yin, Z. W.; Sun, P. P. J. Org.
Chem. 2012, 77, 11339.
(16) (a) Zeng, F. L.; Alper, H. Org. Lett. 2011, 13, 2868. (b) Zhou,
B.; Yang, Y, X.; Li, Y. C. Chem. Commun. 2012, 48, 5163.
(17) Yang, Z. Y.; Chen, X.; Wang, S. Z.; Liu, J. D.; Xie, K.; Wang, A.
W.; Tan, Z. J. Org. Chem. 2012, 77, 7086.
(18) (a) San
́
chez, R. S.; Zhuravlev, F. A. J. Am. Chem. Soc. 2007, 129,
5824. (b) Zhuravlev, F. A. Tetrahedron Lett. 2006, 47, 2929.
2797
dx.doi.org/10.1021/jo302754c | J. Org. Chem. 2013, 78, 2792−2797