Table 1. Optimization Studies in the Synthesis of
2-Acylbenzothiazole
Scheme 1. Multipathway Coupled Domino Strategy
additive
(mmol)
oxidant
(mmol)
temp
yield
(%)c
entry
(°C)
1a
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
NIS (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.5)
I2 (1.5)
I2 (2.0)
I2 (2.0)
IBX (1.2)
IBX (1.2)
IBX (1.2)
IBX (1.2)
IBX (1.2)
TBHP (1.2)
H2O2 (1.2)
DMP (1.2)
DIB (1.2)
BTI (1.2)
HTIB (1.2)
IBX (1.2)
IBX (1.5)
IBX (2.0)
IBX (1.5)
70
70
80
90
80
80
80
80
80
80
80
80
80
80
80
10
2b
50
Moreover, many compounds containing a benzothiazole
motif exhibit potential biological activities and medicinal
significance.5 However, only a few methods have been re-
ported to access 2-acylbenzothiazoles.6 In addition, no
examples have been reported for the synthesis of 2-acyl-
benzothiazole from multiform substrates arylethenes or
arylacetylenes, or 2-hydroxy-aromatic ketones or carbi-
nols. Herein, we reported a simple, metal-free, and multi-
pathway method to synthesize 2-acylbenzothiazoles from
different substrates.
3b
56
4b
55
5b
40
6b
<20
n.r.
n.r.
n.r.
n.r.
n.r.
68
7b
8b
9b
10b
11b
12b
13b
14b
15b
74
To initiate our study, the reaction of styrene (1a) with
2-aminobenzenethiol (2a) was chosen as a model reac-
tion in the presence of different oxidants and additives
in DMSO. The reaction of styrene (1a, 1 mmol) and 2-
aminobenzenethiol (2a, 1 mmol) with I2/IBX (1.1 mmol/1.2
mmol) could only afford the desired product in very low
yield at 70 °C in DMSO (Table 1, entry 1). It was found,
however, that the desired product could be obtained in 50%
yield when styrene (1a, 1 mmol) and I2/IBX (1.1 mmol/1.2
mmol) were mixed and heated at 70 °C for 1.5 h, with the
subsequent addition of 2-aminobenzenethiol (2a, 1 mmol)
to the mixture for another 1 h at 70 °C. Then, sequential
addition coupled domino methodology was adopted to
form the product. Different temperatures were scanned to
improve the yield, and 80 °C was found to be the most
optimal for the domino reaction (Table 1, entries 2À4).
The additive NIS was also found to promote the reaction,
allowing a moderate yield (Table 1, entry 5). In addition,
the other oxidants, such as TBHP, H2O2, DMP, DIB, BTI,
and HTIB, were tested for this reaction in the presence of
molecular iodine. Among them, IBX was found to be the
most optimal oxidant for the transformation (Table 1,
entries 6À11). Finally as concluded above, the optimal
reaction conditions for the reaction turned out to be sty-
rene 1a (1.1 mmol) and 2-aminobenzenethiol 2a (1.2 mmol),
at 80 °C with I2/IBX (2.0 mmol/1.5 mmol) in DMSO
(entry 15).
75
75
a Reaction conditions: 1a (1.0 mmol), 2a (1.0 mmol), I2 (1.1 mmol),
IBX (1.2 mmol) was heated at 70 °C in DMSO. b Reaction conditions:
1a (1.0 mmol), I2, oxidant was heated for 1.5 h and then added 2a
(1.2 mmol) in DMSO. c Isolated yield. IBX = o-iodoxy-benzoic acid,
TBHP = tert-butyl hydroperoxide, DMP = 1,1,1-triacetoxy-1,1-dihydro-
1,2-benziodoxol-3(1H)-one, DIB = (diacetoxyiodo)benzene, BTI = [bis-
(trifluoroacetoxy)iodo]benzene, HTIB = [Hydro(tosyloxy)iodo]benzene.
Scheme 2, both electron-donating and -withdrawing groups
attached to arylethenes 1 were all suitable for this protocol.
Arylethenes with different substituents, such as Me, OMe,
t-Bu, Me2, Cl, Br, and CN, could all provide the corre-
sponding products with 56À75% yields (Scheme 2, 3aÀk).
In addition, 2-naphthyl ethene 1l and biphenyl ethene 1m
also reacted with 2-aminobenzenethiol 2a to obtain the de-
sired products in 66% and 50% yields (Scheme 2, 3l and 3m).
This indicated that the electronic and steric nature
of the arylethenes had little influence on the reaction effi-
ciency. In addition, 2-amino-4-chlorobenzenethiol (2b)
could also react with arylethenes 1 to afford the correspond-
ing products in moderate to good yields (3nÀp, 60À82%).
Encouraged by the results obtained with arylethenes, we
focused our attention on the terminal aromatic alkynes.
Then, we optimized the reaction conditions on the basis of
phenylacetylene 4a and 2-aminobenzenethiol 2a (see Sup-
porting Information). The reaction gave a moderate yield
in the presence of I2 and IBX. The otheroxidants, however,
only gave a trace amount of desired product. To our
delight, the yield was increased when NIS was selected as
an additive. After extensive optimization, it was found that
the reaction could perform at 80 °C with the additive NIS
(1.5 mmol) in the absence of an oxidant in DMSO.
With the optimal conditions in hand, the scope of the
transformation was investigated, mediated with I2/IBX,
and the results were summarized in Scheme 2. As shown in
(5) (a) Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003,
103, 893. (b) McKee, M. L.; Kerwin, S. M. Bioorg. Med. Chem. 2008, 16,
1775. (c) Kiumars Bahrami, K.; M. Mehdi Khodaei, M. M.; Naali, F.
J. Org. Chem. 2008, 73, 6835.
(6) (a) Mu, X. J.; Zou, J. P.; Zeng, R. S.; Wu, J. C. Tetrahedron Lett.
2005, 46, 4345. (b) Hyvl, J.; Srogl, J. Eur. J. Org. Chem. 2010, 2849. (c)
Fan, X. S.; He, Y.; Wang, Y. Y.; Xue, Z. K.; Zhang, X. Y.; Wang, J. J.
Tetrahedron Lett. 2011, 52, 899.
The scope of both terminal aryl alkynes (4) and o-
aminobenzenethiols (2) was also explored (Table 2). The
results demonstrated that the electronic nature of the
Org. Lett., Vol. 14, No. 17, 2012
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