Syntheses of 2-arylbenzothiazoles from flash vacuum pyrolyses and photolyses of 2-methylthio-N-(arenylidene)anilines

Article abstract of DOI:10.1016/j.tetlet.2008.04.118

Flash vacuum pyrolyses and photolyses of 2-methylthio-N-(arenylidene)anilines 2a-h are new and convenient methods for the syntheses of 2-arylbenzothiazoles 1a-h.

Full text of DOI:10.1016/j.tetlet.2008.04.118

Tetrahedron Letters 49 (2008) 4145–4146
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Tetrahedron Letters
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Syntheses of 2-arylbenzothiazoles from flash vacuum pyrolyses and
photolyses of 2-methylthio-N-(arenylidene)anilines
*
Chin-Hsing Chou , Pin-Chih Yu, Bo-Chi Wang
Department of Chemistry and Center for Nanoscience and Nanotechnology, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Flash vacuum pyrolyses and photolyses of 2-methylthio-N-(arenylidene)anilines 2a–h are new and
convenient methods for the syntheses of 2-arylbenzothiazoles 1a–h.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 6 March 2008
Revised 18 April 2008
Accepted 22 April 2008
Available online 24 April 2008
2-Arylbenzothiazoles 1 have been known as important and use-
ful compounds for pharmaceutical organic synthesis, as anticancer
and Alzheimer’s disease agents.1–9 There have been numerous
reports for the synthetic routes of these compounds, such as micro-
wave assisted,10,11 ionic liquid,12 solid phase,13 electrooxidation,14
and the catalytic synthesis with Pd, Cu, Mn, Sc, etc.15–21 Recently,
we have prepared 1 from flash vacuum pyrolyses (FVP) and photo-
lyses of 2-methylthio-N-(arenylidene)anilines 2. We wish to report
our results herein.
2-Methylthio-N-(arenylidene)anilines 2a–h were prepared in
quantitative yields from condensation of aryl aldehydes 3a–h
and o-(methylthio)aniline (4) (Scheme 1).22 FVP of 2a–g were
performed using the pyrolysis set-up that has been previously de-
scribed.23 The tube furnace was maintained at temperatures rang-
ing between 750 and 850 °C. A sample of 2 (100–200 mg) was
placed into the sample chamber and the system was evacuated
to ca. 1 Â 10À2 Torr. The pyrolysis process was completed in 1 h.
Pyrolysis at 800 °C and ca. 1 Â 10À2 Torr appeared to be the
optimum reaction conditions for our study. FVP of 2a–g at temper-
atures lower than 800 °C would leave unreacted starting materials,
whereas FVP of 2a–g at temperatures higher than 850 °C would
give lower yields of the desired products 1a–g. FVP of 2a–e gave
2-arylbenzothiazoles 1a–e as the major products and benzothi-
azole (5) as the minor one (Table 1). However, FVP of 2f and 2g,
in addition to the corresponding 2-arylbenzothiazoles 1f and 1g,
and 5, also gave by-products 2-indolylbenzothiazole (6) and
phenanthridine (7), respectively. The yields for the pyrolysis prod-
ucts from FVP of 2a–g are listed in Table 1. With the exception of
2d and 2g which gave low yields (<50%) of 1d and 1g, FVP of
2a–c and 2e–f gave moderate to good yields of the corresponding
2-arylbenzothiazoles.
A mechanism to account for the formation of 2-arylbenzo-
thiazoles 1a–g from FVP of 2a–g is proposed as shown in Scheme
2. Under the pyrolysis conditions, elimination of a methyl radical
from 2 followed by cyclization of the resulting thiophenoxyl radi-
cal would lead to the final product 1. Elimination of an aryl radical
Table 1
Pyrolysis products from FVP of 2-methylthio-N-(arenylidene)anilines 2a–g
Ar
N
N
S
N
S
FVP
Ar
+
800 ºC
H CS
3
-2
SCH3
NH2
1x10 Torr
2a-g
1a-g
5
O
Ar
N
H3CS
toluene,
- H2O
Substrate
Ar
Ph
2-Furyl
2-Thienyl
2-Benzo[b]furyl
2-Benzo[b]thienyl
2-(N-methyl)indolyl
Producta,b (yield, %)
+
Ar
H
2a
2b
2c
2d
2e
2f
1a (85)
1b (73)
1c (69)
1d (40)
5 (6)
5 (8)
5 (2)
5 (2)
5 (7)
5 (5)
2a-h
]furyl;
3a-h
4
1e (65)
a, Ar = phenyl; b, Ar = 2-furyl; c, Ar = 2-thienyl; d, Ar = 2-benzo[
e, Ar = 2-benzo[ ]thienyl; f, Ar = 2-(N-methyl)indolyl; g, Ar = 2-chlorophenyl;
h, Ar = 2,4-dimethoxyphenyl
b
b
1f (53)
6 (Ar = 2-indolyl, 23)
1g (45)
2g
2-Chlorophenyl
5 (15)
(7, 10)
Phenanthridine
Scheme 1.
a
The yields of products were measured by quantitative analysis of 1H NMR
analysis with dibromomethane as an integration standard.
* Corresponding author. Tel./fax: +886 7 5253915.
E-mail address: ch-chou@mail.nsysu.edu.tw (C.-H. Chou).
b
All products were characterized by their NMR and MS spectra.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.118

4146
C.-H. Chou et al. / Tetrahedron Letters 49 (2008) 4145–4146
yields and no side-products. A radical process as shown in Scheme
FVP
Ar
N
S
Ar
N
2 for the FVP method can also be used to account for the formation
of 1a–g from the photolysis method. The yields for the photolysis
products from 2a–g are listed in Table 2. It is apparent that photo-
lysis method is a better synthetic mean for the synthesis of 2-aryl-
benzothiazoles 1 than the pyrolysis method. Furthermore, the
photolysis method is comparable to the commonly used methods
employing 2-aminobenzenethiol as the precursor.11,12,16
-CH3
H3CS
2
N
-H
- Ar
+H
N
S
5
Ar
Ar
S
1
Application of the photolysis method was then employed for
the synthesis of 2-(2,4-dimethoxyphenyl)benzothiazole (1h). In
contrast to the Suzuki coupling approach which failed to prepare
Scheme 2.
1h,15
photolysis
of
2-methylthio-N-(2,4-dimethoxybenzyl-
idene)aniline (2h), under similar reaction conditions, gave 1h in
88% yield.
Cl
Cl
SCH3
FVP
N
N
Ar
N
N
hυ, 300 nm
CH2Cl2, I2, 48 h
Ar
-SCH3
S
H3CS
2g
1h (88%)
2h
In summary, FVP and photolysis of 2-methylthio-N-(arenyl-
idene)anilines 2a–h are new methods to synthesize 2-arylbenzo-
thiazoles 1a–h. However, for the compounds under study, the
photolysis method gives higher yields and cleaner products, as
compared to the FVP method. We are currently extending our
study to the other heterocyclic systems.
Cl
-Cl
N
N
7
Scheme 3.
Acknowledgement
Table 2
Products from photolysis of 2-methylthio-N-(arenylidene)anilines 2a–f
We thank the National Science Council of the Republic of China
for financial support.
Ar
N
N
S
hυ, 300 nm
CH Cl , I , 48 h
Ar
References and notes
H CS
3
2
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2e
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analysis with dibromomethane as an integration standard.
b
All products were characterized by their NMR and MS spectra.
from 1 then gave minor product, benzothiazole (5). By the same
token elimination of a methyl radical from 1f would give 6.
The mechanism for the formation of 7 from FVP of 2g is pro-
posed as shown in Scheme 3.
For the purpose of comparison, syntheses of 2-arylbenzo-
thiazoles by the photolysis method have also been studied.
2-Methylthio-N-(arenylidene)anilines 2a–g (1 Â 10À4 M in CH2Cl2,
and with ca. 5 mol % of iodine as catalyst) were irradiated (300 nm)
in a Rayonet apparatus for 48 h. Compounds 2a–g were all con-
verted into the corresponding 2-arylbenzothiazoles 1a–g with high
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