Divergent synthesis of benzo[d]thiazoles by PIFA-mediated cyclization of β-oxo thioamides

Article abstract of DOI:10.1071/CH11330

Efficient and divergent synthesis of benzo[d]thiazoles is developed from readily available b-oxo thioamides mediated by hypervalent iodine reagent phenyliodine bis(trifluoroaceate) (PIFA) based on reaction conditions selection, which involves the formation of a radical cation and its subsequent intramolecular cyclization process.

Full text of DOI:10.1071/CH11330

CSIRO PUBLISHING
Aust. J. Chem. 2012, 65, 121–128
Full Paper
http://dx.doi.org/10.1071/CH11330
Divergent Synthesis of Benzo[d]thiazoles by PIFA-Mediated
Cyclization of b-Oxo Thioamides
A
B
A
A
Peng Huang, Xiaolan Fu, Yongjiu Liang, Rui Zhang,
A B C
, ,
and Dewen Dong
A
Changchun Institute of Applied Chemistry, Chinese Academy of Sciences,
Changchun 130022, P. R. China.
B
Department of Chemistry, Northeast Normal University, Changchun 130024,
P. R. China.
C
Corresponding author. Email: dwdong@ciac.jl.cn
Efficient and divergent synthesis of benzo[d]thiazoles is developed from readily available b-oxo thioamides mediated by
hypervalent iodine reagent phenyliodine bis(trifluoroaceate) (PIFA) based on reaction conditions selection, which
involves the formation of a radical cation and its subsequent intramolecular cyclization process.
Manuscript received: 8 August 2011.
Manuscript accepted: 17 October 2011.
Published online: 28 November 2011.
reagents.[20] Their efficient utilization in metal-free transforma-
tions relies on both the extremely mild reaction conditions
required and the high chemo-selectivity of the oxidization for
a wide range of functionalities such as phenols, amines, sulfides,
and carbonyl compounds.[21]
During the course of our studies on the synthesis of carbo- and
heterocycles based on b-oxo amides,[22] we successfully achieved
efficient syntheses of substituted isothiazol-3(2H)-ones, pyrrolin-
4-ones, and spiro-fused cycloalkano-(C4)-pyrazolin-5-one N-
oxides from readily available 1-carbamoyl-ketene-S,S-acetals,
enaminones, and 1-carbamoyl-1-oximylcycloalkanes, respecti-
vely, in the presence of phenyliodine bis(trifluoroaceate) (PIFA).
By these reactions, intramolecular N–S, N–C, or N–N bonds
are formed.[23]
In connection with these previous studies and following on
from our research on the synthesis of highly valuable hetero-
cycles through an oxidative process, we prepared a series of
b-oxo thioamides from b-oxo amides and examined their
reactivity towards the hypervalent iodine reagent PIFA. As a
result of these studies, we have developed a facile and divergent
synthesis of benzo[d]thiazoles by PIFA-mediated intramolecu-
lar C–S bond formation.
Introduction
The benzothiazole ring makes up the core structure of numerous
natural products and synthetic compounds along with diverse
biological properties, such as antitumour,[1] antimicrobial,[2]
antiglutamate/antiparkinson,[3] antiparasitic,[4] calcium channel
antagonist,[5] and enzyme inhibition including aldose reduc-
tase,[6] monoamine oxidase,[7] lipoxygenase,[8] acetylcholines-
terase,[9] cyclooxygenase,[10] thrombine,[11] SARS-CoV 3CL
protease,[12] and HCV helicase.[13] The therapeutic importance
of benzothiazole derivatives and their synthetic utilization as
intermediates in organic chemistry have directed great research
activity towards the construction of the skeleton of this kind of
heterocycle. The most notable method for the synthesis of
benzothiazoles involves the condensation of 2-aminothiophenol
with substituted nitriles, carboxylic acids, aldehydes, acyl
chlorides, or esters.[14] Other methods are reported by means of
oxidative cyclization of thioanilides with a large number of
oxidizing reagents,[15] and transition metal-catalyzed, particu-
larly palladium or copper, intramolecular nucleophilic aromatic
substitution of o-halothioanilides.[16] However, some of these
methods suffer from drastic reaction conditions, tedious work-
up, possibility of side reactions or generation of acidic/metallic
wastes. Therefore, to match the increasing scientific and prac-
tical demands, it is still of continued interest and great impor-
tance to explore simple and efficient synthetic approaches for
the construction of benzothiazoles, especially those with wide
applicability to achieve more elaborate and flexible substitution
patterns.
Results and Discussion
The substrates, b-oxo thioamides 1, were prepared by the
reaction of b-oxo amides with isothiocyanates in ethanol in the
presence of K2CO3 under reflux in excellent yields (up to 96 %)
according to the procedure described in our previous work.[24]
We then selected N-(2-methoxyphenyl)-3-(phenylamino)-3-
thioxopropanamide 1a from a series of substrates 1, see Table 1,
as the model compound to examine its reaction behaviour in the
presence of PIFA and trifluoroacetic acid (TFA).[25] Upon
treatment of substrate 1a with PIFA (2.0 equiv) and TFA
Recently, the synthesis of benzothiazoles by oxidative cycli-
zation of thioanilides with varied hypervalent iodine reagents
were reported.[17–19] Hypervalent iodine reagents have been
extensively used as oxidation reagents in synthetic organic
chemistry because of their ready availability, low toxicity, ease
of handling, and reactivity similar to that of heavy metal
Journal compilation Ó CSIRO 2012
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122
P. Huang et al.
S
O
S
S
O
O
PIFA/TFA
CH2Cl2, 0ЊC
N
N
H
N
N
H
N
H
N
H
OMe
O
OMe
OMe
2a (38 %)
1a
3a (26 %)
Scheme 1. Reaction of 1a with phenyliodine bis(trifluoroaceate) (PIFA)/trifluoroacetic acid (TFA).
Table 1. Synthesis of benzo[d]thiazoles 2 by phenyliodine bis(trifluoroaceate) (PIFA)-mediated oxidative cyclization of b-oxo thioamides 1
S
O
S
O
PIFA (1.0equiv)
CH2Cl2, rt
R1
R1
N
H
NHR2
N
NHR2
1
2
EntryA
1
R1
R2
2
YieldB [%]
1
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
2-MeOC6H4
2a
73
2
4-MeOC6H4
2-MeC6H4
4-MeC6H4
2b
2c
2d
2e
2f
66
3
68
4
62
5
2,4-Me2C6H3
C6H5
75
6
65
7
1g
1h
1i
4-ClC6H4
Me
2g
2h
2i
51
8
60
9
4-MeO
C6H5
64
10
11
12
13
14
1j
2,4-Me2
4-Cl
C6H5
2j
71
1k
1l
2,4-Me2C6H3
2,4-Me2C6H3
C6H5
2k
2l
58
4-CF3
3-Me
3-Me
46
61(2/1)C
67(2/1)C
1m
1n
2m 1/2m 2
]
2n 1/2n 2
] ]
]
4-MeOC6H4
AReagents and conditions: 1 (1.0 mmol), PIFA (1.0 mmol), CH2Cl2 (anhydrous, 100 mL), rt, 15–30 min.
BIsolated yield.
CThe data in brackets: ratio of regioisomers 2.
(1.0 equiv) in CH2Cl2 at 08C for 2.0 h, the reaction proceeded
smoothly as indicated by TLC, and furnished two products
after workup and purification by column chromatography.
The products were characterized as 2-(benzo[d]thiazol-2-yl)-N-
(2-methoxyphenyl)-acetamide 2a and 2-(benzo[d]thiazol-2-yl)-
N-(2-methoxyphenyl)-2-oxoacetamide 3a, respectively, based
on their spectroscopic and analytical data (Scheme 1). Obvi-
ously, the formation of 3awas attributed to further oxidation of
2a with excess PIFA.
The reaction conditions, including the PIFA/TFA/1a ratio,
the reaction temperature, and the concentration of PIFA were
then investigated to optimize the yield of 2a. It was observed that
when 1a, PIFA (1.0 equiv), and TFA (3.0 equiv) were subjected
to CH2Cl2 at 08C for 20 min, the reaction produced 2a in 62 %
yield. Without addition of TFA, the reaction of 1a and PIFA
(1.0 equiv) could occur to furnish 2a, which suggested that the
additive TFA had no significant influence on the present reac-
tion. Indeed, the reaction of 1a and PIFA (1.0 equiv) could
proceed in other solvents, such as dichloroethane, acetonitrile,
and N,N-dimethyformamide, but the yield of 2a was slightly
decreased. It was of interest to note that when the reaction of 1a
and PIFA was conducted in anhydrous CH2Cl2 even with excess
of PIFA (2.0 equiv) and prolonged reaction time (2.0 h), only 2a
could be obtained. After a series of optimization experiments,
CH2Cl2 was proved to be the best solvent among those tested
and the yield of 2a reached 73 % when the reaction of 1a with
PIFA (1.0 equiv, 0.01 M) was performed in anhydrous CH2Cl2
at room temperature for 20 min (Table 1, entry 1).
Having established the optimal conditions for the cyclization
process to benzo[d]thiazoles 2, we intended to determine
its scope with respect to the amide and thioamide motifs.
Thus, a series of b-oxo thioamides 1b–n were subjected to
PIFA under the identical conditions as for 2a in Table 1 (entry
1), and some of the results are listed in Table 1. It was observed
that all the reactions of 1b–h with electron-donating and
electron-withdrawing aryl amide groups or an alkyl amide
group proceeded smoothly to afford the corresponding benzo
[d]thiazoles 2b–h in moderate to good yields (Table 1, entries
2–8). Under identical conditions, substrates 1i–l bearing elec-
tron-donating and electron-withdrawing aryl thioamide groups
were also allowed to react with PIFA to give the corresponding
benzo[d]thiazoles 2i–l in moderate yields (Table 1, entries
9–12). In the cases of substrates 1m and 1n, the corresponding
benzo[d]thiazoles 2m and 2n were obtained as a pair of
benzannulated regioisomers with a ratio of 2:1 (Table 1, entries
13 and 14, and see Supplementary Material).
In the next studies, we envisaged to optimize the reaction
conditions for the synthesis of benzo[d]thiazole 3a. To our
delight, 3a could be exclusively synthesized by subjecting 1a
and 2.5 equivalents of PIFA to CH2Cl2 at room temperature for
5.0 h. However, product 3a was not detectable within the
reaction system even when anhydrous CH2Cl2 was employed,

Synthesis of Benzo[d]thiazoles
123
Table 2. Synthesis of benzo[d]thiazoles 3 by phenyliodine bis(trifluoroaceate) (PIFA)-mediated oxidative cyclization of b-oxo thioamides 1
S
O
S
O
PIFA (3.0 equiv)
NHR2
CH2Cl2/H2O, rt
R1
R1
N
NHR2
N
H
O
1
3
EntryA
1
R1
R2
3
YieldB [%]
1
1a
1b
1c
1d
1e
1f
H
H
H
H
H
H
H
H
2-MeOC6H4
4-MeOC6H4
2-MeC6H4
4-MeC6H4
2,4-Me2C6H3
C6H5
3a
3b
3c
3d
3e
3f
62
57
55
52
61
58
49
54
57
60
46
2
3
4
5
6
7
1g
1h
1i
4-ClC6H4
Me
3g
3h
3i
8
9
4-MeO
2,4-Me2
4-Cl
C6H5
10
11
1j
C6H5
3j
1k
2,4-Me2C6H3
3k
AReagents and conditions: 1 (1.0 mmol), PIFA (3.0 mmol), CH2Cl2 (100 mL), H2O (5.0 mmol), rt, 3.0–5.0 h.
BIsolated yield.
which indicated that the small amount of water in CH2Cl2 might
play an important role during the transformation from 1a to 3a.
In light of this, we added a drop of water to solvent CH2Cl2 and
performed the reaction of 1a and PIFA in such solvent. As a
result, the reaction proceeded smoothly to afford 3a and the
reaction rate was significantly accelerated. After a series of
experiments, optimal conditions for the synthesis of 3a were
obtained when the reaction of 1a with PIFA (3.0 equiv, 0.03 M)
was performed in CH2Cl2 (with 5.0 equiv of H2O) at room
temperature for 4.0 h, whereby the yield of 3a reached 62 %
(Table 2, entry 1). Under the same conditions as for 3a, the
synthesis of benzo[d]thiazoles 3 was carried out, and some
results are summarized in Table 2. It was observed that b-oxo
thioamides 1b–h with varied amide groups underwent a cycli-
zation reaction to give the corresponding benzo[d]thiazoles
3b–h in moderate yields (Table 2, entries 2–8). The versatility
of the protocol proved to be suitable for 1i–k bearing variable
thioamide groups affording the corresponding benzo[d]thia-
zoles 3i–k in moderate yields (Table 2, entries 9–11).
The results shown above demonstrate the efficiency and
synthetic value of the cyclization reaction with respect to
b-oxo thioamides 1 bearing variable amide and thioamide
groups.* Therefore, we have provided a novel protocol for the
divergent synthesis of benzo[d]thiazoles of types 2 and 3.
It should be noted that the richness of the functionality,
e.g., thiazole, activated methylene, and amide groups on
the benzo[d]thiazoles of type 2 may render them extremely
versatile as synthons in further synthetic transformations.[26] In
particular, benzo[d]thiazoles of type 3 can be regarded as both
benzothiazol-2-yl ketones[27] and a-ketoamides. a-Ketoamides
are frequently encountered as structural subunits in many
natural products, and very important synthetic intermediates
as well.[28]
On the basis of the obtained results together with some
literature results, a plausible mechanism for the synthesis of
benzo[d]thiazoles 2 and 3 is presented in Scheme 2. b-Oxo
thioamide 1 initially reacts with PIFA to generate a radical
cation A by a single electron transfer (SET) process,[19,29]
followed by an intramolecular cyclization reaction to yield
benzo[d]thiazole 2 through radical B. Further oxidization reac-
tion of 2 by PIFA occurs to generate intermediate C, which is
attacked by water to give intermediates D and E when aqueous
solvent is employed.[30,31] In the presence of PIFA, alcohol E is
easily oxidized to give rise to final product 3.[21d,30a,32]
Conclusion
In summary, a facile and divergent synthesis of benzo[d]thia-
zoles of types 2 and 3 has been developed from b-oxo thioa-
mides 1 mediated by PIFA, which involves the formation of a
radical cation, and subsequent intramolecular cyclization under
rather mild experimental conditions. This protocol is associated
with readily available starting materials, mild conditions, good
yields, and a broad range of synthetic potential of the products.
Further work on the utilization and extension of the scope of the
protocol is currently under investigation in our laboratory.
Experimental
Reagents and Instrumentation
All reagents were purchased from commercial sources and used
without treatment, unless otherwise indicated. The products
were purified by column chromatography over silica gel.
*In an experiment, we examined the reaction of N-phenylethanethioamide in the presence of PIFA, but only a desulfurized product N-phenylacetamide was
obtained in 64 % isolated yield. The result suggested that the amide functionality was essential for the PIFA-mediated oxidative cyclization reaction of
arylthioamide 1. For selected work on PIFA-mediated desulfurization of thioamides, see ref. [19 ].
S
O
PIFA (3.0 equiv)
CH2Cl2/H2O, rt
N
H
N
H

124
P. Huang et al.
H
S
O
S
ϪHϩ
ϩ
SH
O
O
R1
PIFA
SET
R1
R1
.
NHR2
.
NHR2
N
NHR2
N
H
N
1
A
B
Ϫe
ϪHϩ
ϩOH
S
S
OH
H2O
S
O
R1
R1
PIFA
R1
Ϫe
NHR2
N
NHR2
N
NHR2
N
ϪHϩ
2
D
OH
C
ϪHϩ
S
O
S
O
R1
R1
PIFA
NHR2
N
NHR2
N
O
3
E
OH
Scheme 2. Plausible mechanism for the reaction of b-oxo thioamides 1 with phenyliodine bis(trifluoroaceate) (PIFA).
1H NMR and 13C NMR spectra were recorded on a Varian Unity
spectrometer at 300 and 75 MHz, respectively, with TMS as
internal standard. Mass spectra were recorded on an Agilient
1100 LCMsD spectrometer. IR spectra (KBr) were recorded
on a Magna-560 FTIR spectrophotometer in the range of
400–4000 cmꢀ1. Melting points were determined on a TECH X-
4 micro-melting point apparatus. Elemental analyses were car-
ried out on a Perkin–Elmer PE-2400 analyzer.
137.1, 166.5, 194.1. Anal. Calc. for C17H17ClN2OS: C 61.34, H
5.15, N 8.42. Found: C 61.48, H 5.09, N 8.26.
Compound 1l
White solid, mp 167–1698C. dH (400 MHz, DMSO) 2.19
(s, 3H), 2.25 (s, 3H), 3.98 (s, 2H), 6.97 (d, J 8.0, 1H), 7.03 (s,
1H), 7.27 (d, J 8.0, 1H), 7.80 (d, J 8.4, 2H), 8.17 (d, J 8.4, 2H),
9.52 (s, 1H), 12.08 (s, 1H). dC (100 MHz, DMSO) 17.7, 20.4,
54.6, 122.8, 122.9, 124.9, 125.0, 125.8, 126.4, 130.8, 131.6
(131.7), 133.3 (133.4), 134.4, 142.6 (142.8), 165.3 (165.4),
196.4 (196.5). Anal. Calc. for C18H17F3N2OS: C 59.00, H
4.68, N 7.65. Found: C 59.17, H 4.65, N 7.61.
Physical Data of Compounds 1i–n
1a h are known compounds, their analytical data are in good
]
agreement with those in the literature.[24]
Compound 1m
Compound 1i
White solid,: mp 114–1158C. dH (300 MHz, CDCl3) 2.36
(s, 3H), 4.07 (s, 2H), 7.08 (d, J 7.8, 1H), 7.14–7.19 (m, 1H),
7.28–7.36 (m, 3H), 7.52 (d, J 8.1, 3H), 7.60 (d, J 8.1, 1H), 8.68
(s, 1H), 11.12 (s, 1H). dC (125 MHz, CDCl3) 21.3, 54.5, 120.4,
120.7, 124.1, 125.2, 127.9, 128.6, 129.0, 137.0, 138.3, 138.9,
166.4, 193.7. Anal. Calc. for C16H16N2OS: C 67.58, H 5.67, N
9.85. Found: C 67.51, H 5.53, N 9.77.
White solid, mp 129–1308C. dH (300 MHz, CDCl3) 3.81
(s, 3H), 4.06 (s, 2H), 6.88–6.93 (m, 2H), 7.14–7.19 (m, 1H),
7.31–7.36 (m, 2H), 7.52 (d, J 8.4, 2H), 7.62–7.66 (m, 2H), 8.70
(s, 1H), 11.04 (s, 1H). dC (125 MHz, CDCl3) 54.2, 55.4, 113.9,
120.4, 125.1, 129.0, 131.5, 137.0, 158.2, 166.4, 193.2. Anal.
Calc. for C16H16N2O2S: C 63.98, H 5.37, N, 9.33. Found: C
63.82, H 5.48, N 9.41.
Compound 1n
Compound 1j
White solid, mp 115–1168C. dH (500 MHz, CDCl3) 2.35 (s,
3H), 3.79 (s, 3H), 4.08 (s, 2H), 6.84 (d, J 8.5, 2H), 7.08 (d, J 7.5,
1H), 7.28 (m, 1H), 7.41 (d, J 8.5, 2H), 7.53 (s, 1H), 7.60 (d, J 8.0,
1H), 8.77 (s, 1H), 11.35 (s, 1H). dC (125 MHz, CDCl3) 21.4,
54.2, 55.4, 114.1, 120.6, 122.3, 124.0, 127.9, 128.6, 129.8,
138.3, 138.9, 157.0, 166.3, 193.5. Anal. Calc. for C17H18N2O2S:
C 64.94, H 5.77, N 8.91. Found: C 65.03, H 5.82, N 8.88.
White solid, mp 169–1708C. dH (300 MHz, CDCl3) 2.23
(s, 3H), 2.33 (s, 3H), 4.07 (s, 2H), 7.04–7.09 (m, 2H), 7.14–7.19
(m, 1H), 7.32–7.40 (m, 3H), 7.52 (d, J 7.5, 2H), 8.38 (s, 1H),
10.58 (s, 1H). dC (125 MHz, CDCl3) 17.7, 21.1, 53.3, 120.4,
125.1, 126.1, 127.2, 129.0, 131.6, 133.4, 134.4, 137.0, 138.0,
166.3, 195.5. Anal. Calc. for C17H18N2OS: C 68.42, H 6.08, N
9.39. Found: C 68.50, H 6.17, N 9.33.
Compound 1k
Typical Procedure for the Synthesis of Substituted
Benzo[d]thiazoles 2
White solid, mp 157–1588C. dH (300 MHz, DMSO) 2.19
(s, 3H), 2.25 (s, 3H), 3.94 (s, 2H), 6.97 (d, J 8.1, 1H), 7.02
(s, 1H), 7.27 (d, J 8.1, 1H), 7.48 (d, J 9.0, 2H), 7.92 (d, J 9.0, 2H),
9.49 (s, 1H), 11.90 (s, 1H). dC (125 MHz, CDCl3) 18.0, 20.9,
55.1, 123.8, 124.4, 127.1, 128.8, 130.9, 131.4, 131.9, 136.2,
Preparation of 2a is described as an example: To a solution of 1a
(0.30 g, 1.0 mmol) in anhydrous CH2Cl2 (100 mL) was added
PIFA (0.43 g, 1.0 mmol) in one portion at room temperature.
After being stirred for 15 min, the reaction mixture was

Synthesis of Benzo[d]thiazoles
125
quenched with saturated aqueous NaHCO3 (50 mL). The or-
ganic layer was washed with water (3 ꢁ 50 mL), dried over
anhydrous MgSO4, filtered, and concentrated under vacuum.
The residue was purified by flash column chromatography
(silica gel, petroleum ether/ethyl acetate, 8:1) to give the product
2a (0.21 g, 73 %) as a pale solid.
Compound 2f
Pale solid, mp 161–1628C. dH (300 MHz, CDCl3) 4.22
(s, 2H), 7.09–7.14 (m, 1H), 7.30–7.35 (m, 2H), 7.40–7.45
(m, 1H), 7.50–7.58 (m, 3H), 7.89 (d, J 7.8, 1H), 8.05 (d, J 7.8,
1H), 9.64 (s, 1H). dC (125 MHz, CDCl3) 41.5, 120.0, 121.7,
122.7, 124.5, 125.5, 126.5, 129.0, 134.8, 137.6, 152.6, 164.4,
164.8. Anal. Calc. for C15H12N2OS: C 67.14, H 4.51, N 10.44.
Found: C 67.23, H 4.48, N 10.61.
Selected Data for Compounds 2
Compound 2a
Compound 2g
Pale solid, mp 149–1518C. dH (300 MHz, CDCl3) 3.88
(s, 3H), 4.24 (s, 2H), 6.87 (d, J 8.1, 1H), 6.93–6.99 (m, 1H),
7.02–7.08 (m, 1H), 7.40–7.45 (m, 1H), 7.50–7.55 (m, 1H), 7.90
(d, J 8.1, 1H), 8.06 (d, J 8.1, 1H), 8.38 (dd, J1 8.1, J2 1.5, 1H),
9.65 (s, 1H). dC (125 MHz, CDCl3) 42.1, 55.7, 110.0, 119.8,
120.9, 121.6, 122.6, 124.0, 125.3, 126.3, 127.5, 135.1, 148.2,
152.9, 164.3, 164.4. MS Calc. m/z 298.1. Found: 299.1
[M þ 1]þ. Anal. Calc. for C16H14N2O2S: C 64.41, H 4.73, N
9.39. Found: C 64.24, H 4.81, N 9.46.
Pale solid, mp 163–1648C. dH (300MHz, CDCl3) 4.22 (s, 2H),
7.29 (d, J 8.7, 2H), 7.41–7.47 (m, 1H), 7.51–7.56 (m, 3H), 7.90
(d, J 7.8, 1H), 8.05 (d, J 7.8, 1H), 9.83 (s, 1H). dC (125MHz,
CDCl3) 41.3, 121.2, 121.7, 122.7, 125.7, 126.6, 129.0, 129.5,
134.7, 136.3, 152.6, 164.4, 164.7. Anal. Calc. for C15H11ClN2OS:
C 59.50, H 3.66, N 9.25. Found: C 59.57, H 3.54, N 9.36.
Compound 2h
Pale solid, mp 101–1038C. dH (300 MHz, CDCl3) 2.87
(d, J 4.8, 3H), 4.06 (s, 2H), 7.20 (s, 1H), 7.38–7.44 (m, 1H),
7.47–7.53 (m, 1H), 7.88 (d, J 8.1, 1H), 8.01 (d, J 8.1, 1H). dC
(125 MHz, CDCl3) 26.4, 40.8, 121.5, 122.5, 125.1, 126.1, 135.1,
152.6, 164.7, 167.3. nmax (KBr)/cmꢀ1 3297, 3093, 3058, 2939,
2903, 1651, 1596, 1560, 1521, 1454, 1436, 1395, 1352, 1249,
1132, 760, 724. Anal. Calc. for C10H10N2OS: C 58.23, H 4.89, N
13.58. Found: C 58.36, H 4.76, N 13.49.
Compound 2b
Pale solid, mp 151–1538C. dH (300 MHz, CDCl3) 3.79
(s, 3H), 4.21 (s, 2H), 6.86 (d, J 8.4, 2H), 7.41–7.55 (m, 4H),
7.90 (d, J 7.8, 1H), 8.05 (d, J 7.8, 1H), 9.43 (s, 1H). dC (125 MHz,
CDCl3) 41.3, 55.3, 114.0, 121.6, 121.8, 122.5, 125.3, 126.3,
130.7, 134.8, 152.5, 156.4, 164.4, 164.8. nmax (KBr)/cmꢀ1 3252,
3061, 2936, 2837, 1660, 1608, 1536, 1511, 1455, 1435, 1411,
1402, 1244, 1166, 1114, 1028, 827, 760, 727. Anal. Calc. for
C16H14N2O2S: C 64.41, H 4.73, N 9.39. Found: C 64.46, H 4.69,
N 9.28.
Compound 2i
Reddish solid, mp 125–1278C. dH (300 MHz, CDCl3) 3.89
(s, 3H), 4.16 (s, 2H), 7.09–7.14 (m, 2H), 7.30–7.36 (m, 3H), 7.57
(d, J 7.5, 2H), 7.93 (d, J 9.0, 1H), 9.55 (s, 1H). dC (125 MHz,
CDCl3) 41.4, 55.8, 104.0, 115.8, 120.0, 123.1, 124.5, 128.9,
136.2, 137.7, 147.1, 157.9, 161.9, 164.8. Anal. Calc. for
C16H14N2O2S: C 64.41, H 4.73, N 9.39. Found: C 64.53, H
4.65, N 9.28.
Compound 2c
Pale solid, mp 151–1528C. dH (300MHz, CDCl3) 2.35 (s, 3H),
4.26 (s, 2H), 7.03–7.08 (m, 1H), 7.17–7.22 (m, 2H), 7.41–7.47
(m, 1H), 7.51–7.56 (m, 1H), 7.91 (d, J 7.8, 1H), 8.01(d, J 8.1, 1H),
8.06 (d, J 8.1, 1H), 9.88 (s, 1H). dC (125MHz, CDCl3) 18.0, 41.1,
121.6, 121.9, 122.4, 124.7, 125.4, 126.4, 126.6, 128.3, 130.3,
134.6, 135.9, 152.5, 164.3, 165.0. Anal. Calc. for C16H14N2OS:
C 68.06, H 5.00, N 9.92. Found: C 68.28, H 4.89, N 9.87.
Compound 2j
Pale solid, mp 161–1628C. dH (300 MHz, CDCl3) 2.46
(s, 3H), 2.78 (s, 3H), 4.18 (s, 2H), 7.09–7.16 (m, 2H), 7.32–
7.37 (m, 2H), 7.51 (s, 1H), 7.60 (d, J 7.5, 2H), 10.25 (s, 1H).
dC (125 MHz, CDCl3) 18.4, 21.5, 40.9, 118.8, 119.6, 124.3,
128.7, 129.0, 131.8, 134.5, 135.6, 137.8, 149.9, 162.6, 164.6.
nmax (KBr)/cmꢀ1 3262, 3039, 2906, 1660, 1599, 1526, 1498,
1444, 1396, 1250, 1188, 1116, 850, 838, 746, 692. Anal. Calc.
for C17H16N2OS: C 68.89, H 5.44, N 9.45. Found: C 69.03,
H 5.50, N 9.37.
Compound 2d
Pale solid, mp 153–1548C. dH (300 MHz, CDCl3) 2.30 (s,
3H), 4.21 (s, 2H), 7.11 (d, J 7.8, 2H), 7.42–7.54 (m, 4H), 7.88 (d,
J 7.8, 1H), 8.04 (d, J 7.8, 1H), 9.49 (s, 1H). dC (125 MHz,
CDCl3) 20.8, 41.5, 120.1, 121.6, 122.6, 125.4, 126.3, 129.3,
134.1, 134.9, 135.0, 152.5, 164.6, 164.9. nmax (KBr)/cmꢀ1 3246,
3031, 2917, 1660, 1594, 1533, 1513, 1455, 1434, 1400, 1245,
1185, 1117, 816, 759, 728. Anal. Calc. for C16H14N2OS: C
68.06, H 5.00, N 9.92. Found: C 68.13, H 5.08, N 9.83.
Compound 2k
Pale solid: mp 204–2058C. dH (300 MHz, DMSO) 2.18
(s, 3H), 2.25 (s, 3H), 4.13 (s, 2H), 6.98 (d, J 7.8, 1H), 7.04
(s, 1H), 7.27 (d, J 8.1, 1H), 7.53 (dd, J1 8.1, J2 2.1, 1H), 7.97
(d, J 8.7, 1H), 8.25 (s, 1H), 9.76 (s, 1H). dC (125 MHz, (D6)
DMSO) 18.2, 21.0, 41.5, 122.2, 123.9, 125.5, 126.9, 127.0,
130.0, 131.3, 132.3, 133.7, 135.2, 137.4, 151.5, 166.4, 167.1.
Anal. Calc. for C17H15ClN2OS: C 61.72, H 4.57, N 8.47. Found:
C 61.94, H 4.60, N 8.43.
Compound 2e
Pale solid, mp 151–1528C. dH (300 MHz, CDCl3) 2.28
(s, 3H), 2.29 (s, 3H), 4.24 (s, 2H), 7.00 (s, 1H), 7.01 (d, J 7.5,
1H), 7.41–7.46 (m, 1H), 7.50–7.55 (m, 1H), 7.86 (d, J 8.1, 1H),
7.90 (d, J 7.5, 1H), 8.00 (d, J 8.1, 1H), 9.70 (s, 1H). dC (125 MHz,
CDCl3) 17.9, 20.8, 41.2, 121.7, 122.2, 122.5, 125.5, 126.5,
127.1, 128.6, 131.0, 133.3, 134.5, 134.7, 152.6, 164.2, 165.2.
nmax (KBr)/cmꢀ1 3271, 3008, 2912, 1651, 1615, 1591, 1531,
1454, 1435, 1399, 1340, 1268, 1224, 1195, 1119, 827, 754, 726.
Anal. Calc. for C17H16N2OS: C 68.89, H 5.44, N 9.45. Found:
C 69.08, H 5.37, N 9.33.
Compound 2l
Pale solid, mp 168–1698C. dH (400 MHz, DMSO) 2.18
(s, 3H), 2.25 (s, 3H), 4.39 (s, 2H), 6.98 (d, J 6.8, 1H), 7.04
(s, 1H), 7.28 (d, J 6.8, 1H), 7.82 (d, J 8.0, 1H), 8.17 (d, J 8.0, 1H),

126
P. Huang et al.
8.63 (s, 1H), 9.79 (s, 1H). dC (100 MHz, (D6)DMSO) 17.7
(17.9), 20.3 (20.4), 41.1, 120.2, 122.7 (122.9), 124.1, 124.9
(125.0), 126.3 (126.5), 128.6, 130.2, 130.7 (130.9), 133.4, 133.8
(134.0), 134.7, 142.2, 157.6, 165.4, 169.7. Anal. Calc. for
C18H15F3N2OS: C 59.33, H 4.15, N 7.69. Found: C 59.15,
H 4.13, N 7.71.
Compound 3e
Yellowish solid, mp 161–1628C. dH (500 MHz, CDCl3) 2.33
(s, 3H), 2.47 (s, 3H), 7.09 (d, J 8.0, 2H), 7.61–7.67 (m, 2H), 8.05
(d, J 7.5, 1H), 8.12 (d, J 8.0, 1H), 8.28 (d, J 7.5, 1H), 10.46
(s, 1H). dC (125 MHz, CDCl3) 18.0, 20.9, 121.7, 122.4, 125.7,
127.5, 127.8, 128.4, 128.8, 131.4, 132.2, 135.8, 138.1, 152.4,
156.1, 160.6, 177.6. nmax (KBr)/cmꢀ1 3252, 3189, 3115, 3056,
2976, 1700, 1681, 1603, 1547, 1478, 1455, 1421, 1322, 1247,
950, 926, 875, 831, 764, 727. Anal. Calc. for C17H14N2O2S:
C 65.79, H 4.55, N 9.03. Found: C 65.85, H 4.46, N 9.10.
Typical Procedure for the Synthesis of Substituted
Benzo[d]thiazoles 3
Preparation of 3a is described as an example: To a solution of 1a
(0.30 g, 1.0 mmol) in CH2Cl2 (100 mL) and water (0.09 g,
5.0 mmol) was added PIFA (1.29 g, 3.0 mmol) in one portion at
room temperature under stirring. After being stirred at room
temperature for 3.0 h, the reaction mixture was quenched with
saturated aqueous NaHCO3 (50 mL). The organic layer was
washed with water (3 ꢁ 50 mL), dried over anhydrous MgSO4,
filtered, and concentrated under vacuum. The residue was pu-
rified by flash column chromatography (silica gel, petroleum
ether/ethyl acetate, 8:1) to give the product 3a (0.19 g, 62 %) as a
yellowish solid.
Compound 3f
Yellowish solid, mp 200–2028C. dH (300 MHz, (D6)DMSO)
7.18–7.23 (m, 1H), 7.40–7.45 (m, 2H), 7.69–7.72 (m, 2H), 7.77
(d, J 7.8, 2H), 8.31–8.36 (m, 2H), 11.16 (s, 1H). dC (125 MHz,
(D6)DMSO) 120.5, 123.9, 125.4, 126.1, 128.4, 129.3, 129.7,
137.5, 138.0, 153.1, 161.6, 161.7, 182.0. Anal. Calc. for
C15H10N2O2S: C 63.81, H 3.57, N 9.92. Found: C 63.67,
H 3.59, N 10.03.
Compound 3g
Selected Data for Compounds 3
Compound 3a
Yellowish solid, mp 231–2328C. dH (300 MHz, (D6)DMSO)
7.49 (d, J 8.7, 2H), 7.70–7.72 (m, 2H), 7.82 (d, J 8.7, 2H), 8.32–
8.34 (m, 2H), 11.30 (s, 1H). dC (125 MHz, (D6)DMSO) 122.3,
123.9, 126.2, 128.4, 129.1, 129.3, 129.6, 137.0, 137.6, 153.1,
161.3, 161.6, 181.5. Anal. Calc. for C15H9ClN2O2S: C 56.88, H
2.86, N 8.84. Found: C 56.79, H 2.91, N 8.91.
Yellowish solid, mp 184–1868C. dH (300 MHz, CDCl3) 4.02
(s, 3H), 6.97–7.08 (m, 2H), 7.16–7.22 (m, 1H), 7.63–7.65
(m, 2H), 8.07 (d, J 6.9, 1H), 8.34 (d, J 8.1, 1H), 8.56 (d, J 8.1,
1H), 10.55 (s, 1H). dC (125 MHz, (D6)DMSO) 56.5, 112.0,
121.1, 121.2, 123.8, 125.9, 126.0, 126.8, 128.4, 129.2, 137.1,
149.7, 152.9, 160.7, 163.5, 180.6. MS Calc. m/z 312.06, Found:
335.05 [M þ Na]þ. Anal. Calc. for C16H12N2O3S: C 61.53,
H 3.87, N 8.97. Found: C 61.58, H 3.77, N 8.85.
Compound 3h
Yellowish solid, mp 144–1458C. dH (300 MHz, CDCl3) 3.09
(d, J 5.1, 3H), 7.60–7.64 (m, 2H), 8.03–8.06 (m, 1H), 8.10 (s,
1H), 8.30–8.33 (m, 1H). dC (125 MHz, CDCl3) 26.4, 122.2,
125.9, 127.5, 128.5, 138.2, 152.5, 159.2, 159.9, 177.8. nmax
(KBr)/cmꢀ1 3365, 3061, 1679, 1538, 1460, 1405, 1320, 1178,
954, 755, 723. Anal. Calc. for C10H8N2O2S: C 54.53, H 3.66,
N 12.72. Found: C 54.61, H 3.79, N 12.68.
Compound 3b
Reddish solid, mp 179–1808C. dH (300 MHz, CDCl3) 3.84
(s, 3H), 6.96 (d, J 9.0, 2H), 7.63–7.67 (m, 2H), 7.72 (dd, J1 ¼ 9.0,
J2 ¼ 2.1, 2H), 8.05–8.08 (m, 1H), 8.34–8.37 (m, 1H), 9.92
(s, 1H). dC (125 MHz, CDCl3) 55.4, 114.4, 121.7, 122.3,
126.1, 127.7, 128.7, 129.4, 138.4, 152.5, 156.3, 157.4, 158.8,
177.8. nmax (KBr)/cmꢀ1 3328, 3048, 3010, 2950, 2835, 1697,
1670, 1611, 1576, 1542, 1510, 1460, 1250, 1154, 1032, 821,
758, 726. Anal. Calc. for C16H12N2O3S: C 61.53, H 3.87, N 8.97.
Found: C 61.45, H 3.96, N 8.91.
Compound 3i
Yellowish solid, mp 187–1888C. dH (300 MHz, CDCl3) 3.96
(s, 3H), 7.22–7.24 (m, 2H), 7.41–7.46 (m, 3H), 7.79 (d, J 7.8,
2H), 8.21 (d, J 9.3, 1H), 9.98 (s, 1H). dC (125 MHz, (D6)DMSO)
56.7, 105.1, 119.4, 120.6, 125.5, 127.2, 129.8, 138.2, 140.0,
148.0, 159.2, 160.8, 162.2, 182.2. Anal. Calc. for C16H12N2O3S:
C 61.53, H 3.87, N 8.97. Found: C 61.39, H 3.95, N 9.04.
Compound 3c
Yellowish solid, mp 138–1408C. dH (300 MHz, CDCl3) 2.52
(s, 3H), 7.14–7.19 (m, 1H), 7.30–7.33 (m, 2H), 7.61–7.69
(m, 2H), 8.05–8.08 (m, 1H), 8.26–8.30 (m, 2H), 10.57 (s, 1H).
dC (125 MHz, CDCl3) 18.0, 121.6, 122.4, 125.6, 125.8, 127.0,
127.8, 128.4, 128.8, 130.6, 134.8, 137.9, 152.3, 156.0, 160.8,
177.4. Anal. Calc. for C16H12N2O2S: C 64.85, H 4.08, N 9.45.
Found: C 64.78, H 4.18, N 9.53.
Compound 3j
Yellowish solid, mp 194–1958C. dH (300 MHz, CDCl3) 2.52
(s, 3H), 2.87 (s, 3H), 7,23 (d, J 7.2, 1H), 7.28 (s, 1H), 7.42–7.47
(m, 2H), 7.66 (s, 1H), 7.80 (d, J 8.4, 2H), 11.07 (s, 1H).
dC (125 MHz, (D6)DMSO) 18.3, 21.9, 120.3, 120.6, 125.3,
129.6, 130.2, 135.3, 137.9, 138.0, 139.8, 150.9, 159.3, 161.5,
181.7. nmax (KBr)/cmꢀ1 3339, 3053, 1674, 1598, 1538,
1444, 1387, 1248, 1143, 1016, 893, 753. Anal. Calc. for
C17H14N2O2S: C 65.79, H 4.55, N 9.03. Found: C 65.87,
H 4.59, N 8.91.
Compound 3d
Yellowish solid, mp 204–2058C. dH (300 MHz, (D6)DMSO)
2.31 (s, 3H), 7.23 (d, J 8.1, 2H), 7.64–7.72 (m, 4H), 8.32–8.33
(m, 2H), 11.06 (s, 1H). dC (125 MHz, (D6)DMSO) 21.1, 120.5,
123.8, 126.1, 128.4, 129.2, 130.0, 134.5, 135.5, 137.5, 153.1,
161.5, 161.6, 182.0. nmax (KBr)/cmꢀ1 3332, 3029, 1678, 1591,
1536, 1510, 1457, 1403, 1260, 1149, 818, 759, 727. Anal. Calc.
for C16H12N2O2S: C 64.85, H 4.08, N 9.45. Found: C 64.78,
H 4.12, N 9.54.
Compound 3k
Yellowish solid, mp 188–1898C. dH (300 MHz, CDCl3) 2.34
(s, 3H), 2.43 (s, 3H), 7.10 (d, J 8.1, 2H), 7.60 (dd, J1 8.7, J2 1.8,
1H), 8.06 (d, J 7.5, 2H), 8.22 (d, J 8.7, 1H), 9.93 (s, 1H).
dC (125 MHz, CDCl3) 17.8, 20.9, 121.7, 121.8, 126.7, 127.5,

Synthesis of Benzo[d]thiazoles
127
128.5, 128.9, 131.4, 131.8, 135.2, 136.0, 139.4, 150.9, 156.2,
159.6, 177.5. Anal. Calc. for C17H13ClN2O2S: C 59.21, H 3.80,
N 8.12. Found: C 59.34, H 3.76, N 8.21.
(d) A. Ben-Alloum, S. Bakkas, M. Soufiaoui, Tetrahedron Lett. 1997,
38, 6395. doi:10.1016/S0040-4039(97)01490-1
(e) Y. Chen, L. Qian, W. Zhang, B. Han, Angew. Chem. Int. Ed. 2008,
47, 9330. doi:10.1002/ANIE.200803381
(f) A. Gellis, N. Boufatah, P. Vanelle, Green Chem. 2006, 8, 483.
doi:10.1039/B601452F
[15] (a) P. Jacobson, Chem. Ber. 1886, 19, 1067. doi:10.1002/CBER.
188601901239
Supplementary Material
NMR spectra of compounds 1i–n, 2a–n, and 3a–k are available
on the Journal’s website.
(b) F. M. Moghaddam, H. Z. Boeini, Synlett 2005, 1612. doi:10.1055/
S-2005-869841
(c) X. Huang, J. Tang, Tetrahedron 2003, 59, 4851. doi:10.1016/
S0040-4020(03)00688-4
(d) D. S. Bose, M. Idrees, Tetrahedron Lett. 2007, 48, 669.
doi:10.1016/J.TETLET.2006.11.105
(e) X. Mu, J. Zou, R. Zeng, J. Wu, Tetrahedron Lett. 2005, 46, 4345.
doi:10.1016/J.TETLET.2005.04.090
Acknowledgement
Financial support of this research by the NNSFC (20872136 and 51073150)
is greatly acknowledged.
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