Ru(III)-catalyzed oxidative reaction in ionic liquid: An efficient and practical route to 2-substituted benzothiazoles and their hybrids with pyrimidine nucleoside

Article abstract of DOI:10.1016/j.tetlet.2010.04.050

An efficient, practical and environmentally benign synthesis of 2-substituted benzothiazoles was developed through RuCl₃-catalyzed oxidative condensation of 2-aminothiophenol with aldehyde in ionic liquid by using air as the oxidant. With this procedure, a series of 2-substituted benzothiazoles and benzothiazole/pyrimidine nucleoside hybrids with antimicrobial activities were efficiently prepared from easily accessible starting materials.

Full text of DOI:10.1016/j.tetlet.2010.04.050

Tetrahedron Letters 51 (2010) 3493–3496
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Ru(III)-catalyzed oxidative reaction in ionic liquid: an efficient
and practical route to 2-substituted benzothiazoles and their hybrids
with pyrimidine nucleoside
*
Xuesen Fan , Yangyang Wang, Yan He, Xinying Zhang, Jianji Wang
School of Chemistry and Environmental Sciences, Henan Key Laboratory for Environmental Pollution Control, Henan Normal University, Xinxiang, Henan 453007, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 January 2010
Revised 6 April 2010
Accepted 13 April 2010
Available online 18 April 2010
An efficient, practical and environmentally benign synthesis of 2-substituted benzothiazoles was
developed through RuCl3-catalyzed oxidative condensation of 2-aminothiophenol with aldehyde in ionic
liquid by using air as the oxidant. With this procedure, a series of 2-substituted benzothiazoles and ben-
zothiazole/pyrimidine nucleoside hybrids with antimicrobial activities were efficiently prepared from
easily accessible starting materials.
Ó 2010 Elsevier Ltd. All rights reserved.
With inherent affinity for diverse biological receptors, 2-substi-
tuted benzothiazoles have shown amazing intrinsic pharmacolog-
ical and biological activities by acting as efficacious antitumor,1
antiviral,2 antimicrobial,3 and antioxidant4 agents. In addition, they
have also found wide applications in the area of organic optoelec-
tronic materials.5 Due to their importance, numerous methods for
the preparation of 2-substituted benzothiazoles have been devel-
oped. Among them, one often used procedure involves the conden-
sation of o-aminothiophenol with carboxylic acids, acyl chlorides,
or esters. But these processes were often accomplished under dras-
tic reaction conditions. An alternative route starting from o-amino-
thiophenol and aldehyde with the assistance of oxidants such as
Sc(OTf)3,6 O2/activated carbon,7 PCC,8 H2O2/CAN,9 and persulfate/
transformations. Meanwhile, the concept of green solvent is of rap-
idly growing popularity due to the increasing awareness of the ad-
verse effect of volatile organic solvents on the environment, and an
expectation has been built up on the use of ionic liquids (ILs) as the
solvent for future due to their nonvolatility, nonflammability, ther-
mal stability, and controlled miscibility.20,21 Furthermore, they are
marching beyond the boundary of green solvent by showing signif-
icant role in promoting or improving various organic
transformation.22
As part of our ongoing research efforts toward the development
of synthetic methodologies for biologically important heterocy-
cles,23 we set to develop a more efficient and practical procedure
for the preparation of 2-substituted benzothiazoles through
RuCl3-catalyzed oxidative condensation of 2-aminobenzenethiol
with aldehyde by using ionic liquid as the reaction medium.
Initially, the reaction of benzaldehyde (1a) and o-aminobenze-
nethiol (2a) was studied under various conditions with regard to
different catalyst, solvent, temperature, and reaction time (Scheme
1). The results are summarized in Table 1. It firstly turned out that
3a could be obtained in a yield of 65% after the mixture of 1a and
2a in [bmim]PF6 (1-butyl-3-methylimidazolium hexafluorophos-
phate) being stirred at 60 °C for 0.5 h in the presence of 3% of RuCl3
(Table 1 entry 1). It should be noted that no added stoichiometric
or excessive oxidant other than air was provided, indicating that
the combination of catalytic amount of RuCl3 and air serves as effi-
cient oxidant for the formation of 3a. To our knowledge, this is the
10
CuSO4 was then developed. More recently, a Bakers’ yeast11a
and a trichloroisocyanuric acid (TCCA) catalyzed11b high efficient
preparation of 2-substituted benzothiazoles from o-aminothiophe-
nol and aldehyde under mild conditions was also reported. In spite
of the merits showed by these procedures, some of them suffer
drawbacks such as tedious workup, low yields, use of stoichiome-
tric or excessive metal reagents, and volatile harmful organic sol-
vents. Therefore, the development of new route with significant
practical value still remains a challenge.
On the other hand, organic transformations catalyzed by ruthe-
nium(III) species have emerged as a focus of attention in recent
years due to their high efficiency and excellent chemoselectivity.
A catalytic amount of ruthenium(III) together with oxidants such
as H2O2,12 CH3CO3H,13 NaIO4,14 oxygen,15 (diacetoxyiodo)benzene
(DIB),16 bromamine-T,17 CeCl3/NaIO4,18 and oxygen/sodium
cyanide19 has been successfully used in an array of oxidative
S
SH
Various conditions
CHO
+
N
NH2
1a
2
3a
* Corresponding author. Tel.: +86 373 332 9261; fax: +86 373 332 6336.
E-mail addresses: xuesen.fan@henannu.edu.cn, xuesen.fan@yahoo.com (X. Fan).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.050

3494
X. Fan et al. / Tetrahedron Letters 51 (2010) 3493–3496
Table 1
Oxidative condensation of 1a and 2a under different reaction conditionsa
Entry
Solvent
Catalyst
Amount of catalyst (equiv)
Time (h)
Temp. (°C)
Yieldb (%)
1
2
2
3
4
5
6
7
8
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmmim]PF6
[bmim]BF4
[bmim]PF6
[bmim]PF6
[bmim]PF6
[bmim]PF6
THF
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
RuCl3
—
RuCl3
InCl3
CeCl3
RuCl3
RuCl3
RuCl3
RuCl3
0.03
0.03
0.03
0.05
0.05
0.1
0.05
0.05
—
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
3
3
2
2
3
60
80
100
60
80
80
80
80
80
80
80
80
Reflux
Reflux
80
65
72
70
78
83
84
63
75
Trace
Tracec
Trace
66
68
62
9
10
11
12
13
14
15
CH3CN
Toluene
CH2Cl2
3
3
3
50
61
Reflux
a
b
c
Reaction conditions: 1 mmol of 1a was used.
Isolated yields.
Under nitrogen atmosphere.
Bu
N
Bu
N
-
-
N+
N+
R
PF6
Me
PF6
Me
H
H
H
N
N
S
NH2
N
O
C
R
R
+
R
H
S
SH
SH
3
A
B
2
1
Ru(II)
Ru(III)
air
Figure 1.
first example in which RuCl3/air acts as an oxidant for the forma-
tion of heterocycles. Further studies showed that under optimized
reaction conditions, 3a could be obtained in a yield of 83% (entry
4). Studies also revealed that in the absence of either RuCl3 (entry
8) or air (entry 9), only trace amount of 3a was formed as indicated
by TLC.
ability to act as a hydrogen bond donor. The formation of the O–
H hydrogen bond from [bmim]+ to the carbonyl oxygen of 1 in-
duces electrophilic activation of aldehyde, which benefits the ini-
tial condensation of 1 with 2 to form an imine intermediate A.
Moreover, it may further form an N–H hydrogen bond with the
in situ-formed imine A and it would accelerate the subsequent
intramolecular nucleophilic cyclization to form intermediate B.
Intermediate B is then oxidized by Ru(III) to give the final product
3. The in situ-formed Ru (II) could be oxidized by air to regenerate
Ru(III) for the next catalytic cycle, accounting for the necessity of
the presence of catalytic amount of Ru(III) and air.
With the optimized reaction conditions, the oxidation of a range
of substrates was then tried to study the scope and limitation of
this new procedure (Scheme 2) and the examples are summarized
in Table 2. It was observed that, with either aromatic or aliphatic
aldehydes, the reactions underwent smoothly, and the correspond-
ing products were obtained in good yields. For aromatic aldehydes
and aminobenzothiols with electron-withdrawing or electron-
donating groups on the phenyl rings, the reactions were run with
almost equal efficiency (Table 2, entries 1–19). On the other hand,
for aminobenzothiol with steric hindered group, the reactions were
slowed down and the yields were lower (Table 2, entries 22–25).
Moreover, various functional groups, such as nitro, methyl, meth-
oxy, and halide groups on the phenyl rings, were well tolerated un-
der this condition.24
In addition, two more ILs, namely [bmim]BF4 (1-tutyl-3-meth-
ylimidazolium tetrafluoroborate) and [bmmim]PF6 (1,2-dimethyl-
3-butyl imidazolium hexafluorophosphate), were employed. It
showed that [bmim][PF6] was superior to [bmim][BF4] in its effi-
ciency (Table 1, entries 4 and 7), presumably due to its hydropho-
bic activation activity. It is postulated that water formed from the
condensation is miscible with hydrophilic [bmim][BF4] and thus
detained, which prevents the reaction from reaching completion.
In contrast, the hydrophobic nature of [bmim][PF6] would create
a micro-environment to drive the equilibrium forward by extrud-
ing water out of the ionic liquid phase and thus result in a higher
conversion. In the case of [bmmim]PF6, with the proton of C-2 on
the imidazole ring being replaced by a methyl group compared
with [bmim]PF6, the yield of 3a dropped to 63% under similar con-
ditions (entry 6).
The oxidative condensation was also run in several conven-
tional organic solvents (Table 1, entries 12–15). It followed that
compared with CH2Cl2, CH3CN, Toluene, or THF, [bmim]PF6 and
[bmim]BF4 not only exhibited an environmental benign nature
but also showed enhanced reactivity by reducing reaction time
and improving the yields significantly.
Based on the above observations, a plausible mechanism for the
RuCl3-catalyzed oxidative formation of 2-substituted benzothia-
zole is depicted in Figure 1. Firstly, the accelerating effect showed
by [bmim]PF6 and [bmim]BF4 compared with conventional organic
solvents and [bmmim]PF6 was attributed to the acidity of the
hydrogen on the 2-position of the imidazolium cation and its
S
N
SH
RuCl3/air
[bmim]PF6, 80ºC
R1CHO
+
R2
R2
R1
NH2
3
1
2
Scheme 2.

X. Fan et al. / Tetrahedron Letters 51 (2010) 3493–3496
3495
R2
Table 2
a
Preparation of 3 with RuCl3/air in [bmim]PF6
O
N
S
O
N
OHC
Entry
R1
R2
Product
Time (h)
Yieldb (%)
NH
SH
N
NH
O
RuCl3/air
[bmim]PF6, 80ºC
R2
+
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
C6H5
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
0.5
0.5
0.5
0.5
1
83
85
80
85
81
82
81
86
84
79
83
88
83
82
83
80
80
80
79
75
76
62
75
60
43
80
78
R3O
O
R3O
NH2
4-BrC6H4
4-CH3OC6H4
4-CNC6H4
2-BrC6H4
2-NO2C6H4
2-ClC6H4
3-NO2C6H4
3-BrC6H4
3-CH3C6H4
C6H5
4-NO2C6H4
4-BrC6H4
4-CH3OC6H4
3-ClC6H4
3-BrC6H4
2-NO2C6H4
2-ClC6H4
2-BrC6H4
CH3CH2CH2
CH3CH2CH2
C6H5
O
O
R4
R4
2
4
5
0.5
1
Scheme 4.
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
1
2
2
4
3
4
6
2
H
H
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
H
4-Cl
3-Cl
3-Cl
3-Cl
3-Cl
4-CH3
4-CH3
Table 3
a
Preparation of 5 with RuCl3/air in [bmim]PF6
Entry
R2
R3
R4
Product
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
9
H
4-Cl
H
4-Cl
H
4-Cl
H
Ac
Ac
Ac
Ac
H
H
H
H
Ac
OAc
OAc
N3
5a
5b
5c
5d
5e
5f
5g
5h
5i
2
2
2
2
3
3
3
3
6
75
77
75
71
70
71
68
66
50
N3
3s
3t
OH
OH
N3
3u
3v
3w
3x
3y
3z
3aa
4-Cl
3-Cl
N3
4-NO2C6H4
3-CH3C6H4
2-NO2C6H4
4-BrC6H4
3-CH3C6H4
OAc
a
Reaction conditions: 1 mmol of 2 and 4, 1 mL of [bmim]PF6, 80 °C.
b
Isolated yields.
2
a
Reaction conditions: 1 mmol of 1 and 2, 1 mL of [bmim]PF6, 80 °C.
Isolated yields.
b
drop in its catalytic activity was observed over each reuse. In these
reactions, the ionic liquid acts as not only solvent and co-catalyst
but also an immobilizing agent for facilitating catalyst recycling.
In conclusion, we have developed a simple, practical and envi-
ronmentally benign procedure for the preparation of 2-substituted
benzothiazoles. This oxidative condensation proceeds under mild
conditions with the catalysis of RuCl3 in [bmim]PF6 by employing
air as the oxidant. Compared with the literature methods, advanta-
ges of this procedure include high efficiency, readily available
starting material and reagents, recyclable reaction medium, and
an environmentally benign nature. To our knowledge, this is the
first example that RuCl3 plays a catalytic role on the oxidation reac-
tion with air as the stoichiometric oxidant. Further studies to
search for more applications of this novel oxidative system and
to evaluate the biological activities of the newly synthesized nucle-
oside derivatives are currently underway and the results will be re-
ported in due course.
In a further aspect, Loiseau and co-workers25 recently reported
a synthesis and in vitro antileishmanial evaluation of a small li-
brary of 5-heteroaryl-substituted-20-deoxyuridine. The nucleoside
derivatives were synthesized therein through two to three steps
and the key step is based on a palladium and cupric salt-catalyzed
Stille cross coupling of protected 5-iodo-20-deoxyuridine with pre-
made aryltin derivatives (Scheme 3).
Considering the tedious procedure, expensive catalyst, and spe-
cially made starting material it involved, we thought it would ben-
efit both synthetic and medicinal chemistries to develop a more
practical method to prepare these nucleoside derivatives. A new
synthetic route was then envisioned by using the methodology
developed in this Letter. Thus, a mixture of the easily made 5-for-
myl-pyrimidine nucleoside (4)26 and commercially available 2 was
treated with [bmim]PF6 at 80 °C in the presence of 5% of RuCl3
(Scheme 4). Very encouragingly, the reactions underwent
smoothly and afforded the pyrimidine nucleoside-benzothiazole
hybrids with good yields (Table 3). The structures of the hybrid
compounds were fully characterized by their spectra data.27
Finally, the recyclability of RuCl3 together with [bmim]PF6 was
studied by using 1a and 2a as the substrates. It turned out that
RuCl3/[bmim]PF6 could be reused directly for a new cycle after
the IL phase was extracted with diethyl ether (10 mL ꢀ 3) and
dried under vacuum at 90 °C overnight. The recovered RuCl3/
[bmim]PF6 was recycled and reused for three times. Only slight
Acknowledgments
This work was financially supported by the National Natural
Science Foundation of China (Nos. 20772025 and 20972042), Inno-
vation Scientists and Technicians Troop Construction Projects of
Henan Province (No. 104100510019), Program for Science & Tech-
nology Innovation Talents in Universities of Henan Province (No.
2008HASTIT006), and the Natural Science Foundation of Henan
Province (Nos. 092300410192 and 094300510054).
O
S
O
N
S
O
N
S
N
I
NH
N
SnBu3
N
NH
NH
K2CO3/MeOH
N
O
AcO
O
O
AcO
HO
Pd(PPh3)2Cl2, CuI (cat.)
Et3N, DMF, 70 ºC
O
O
O
OAc
OAc
Scheme 3.
OH

3496
X. Fan et al. / Tetrahedron Letters 51 (2010) 3493–3496
analytical data of selected compounds are presented as follows: Compound 3d:
References and notes
mp 165–167 °C; 1H NMR (400 MHz, CDCl3) d: 7.47 (t, 1H, J = 7.6 Hz, ArH), 7.56
(t, 1H, J = 7.6 Hz, ArH), 7.80 (d, 2H, J = 8.0 Hz, ArH), 7.96 (d, 1H, J = 8.0 Hz, ArH),
8.13 (d, 1H, J = 8.0 Hz), 8.22 (d, 2H, J = 8.0 Hz, ArH). 13C NMR (100 MHz, CDCl3)
d: 114.1, 118.3, 121.8, 123.8, 126.1, 126.8, 127.9, 132.8, 135.3, 137.5, 154.0,
165.3. MS: m/z 237 (MH)+. Compound 3l: mp 185–187 °C; 1H NMR (400 MHz,
CDCl3) d: 7.43 (dd, 1H, J1 = 2.0 Hz, J2 = 8.4 Hz, ArH), 7.87 (d, 1H, J = 8.4 Hz, ArH),
8.10 (d, 1H, J = 2.0 Hz, ArH), 8.24 (d, 2H, J = 8.4 Hz), 8.36 (d, 2H, J = 8.4 Hz, ArH).
13C NMR (100 MHz, CDCl3) d: 122.6, 123.6, 124.4, 126.7, 128.3, 132.9, 133.7,
138.7, 149.1, 154.8, 166.6. MS: m/z 291 (MH)+. Compound 3t: oil; 1H NMR
(400 MHz, CDCl3) d: 1.07 (t, 3H, J = 7.6 Hz, CH3), 1.90–1.96 (m, 2H, CH2), 3.11 (t,
2H, J = 7.6 Hz, CH2), 7.35 (t, 1H, J = 7.6 Hz, ArH), 7.46 (t, 1H, J = 7.6 Hz, ArH), 7.85
(d, 1H, J = 8.0 Hz, ArH), 7.98 (d, 1H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3) d:
13.7, 23.1, 36.2, 121.4, 122.5, 124.6, 125.8, 126.6, 126.8, 135.1, 153.2, 172.2.
MS: m/z 178 (MH)+. Compound 3w: mp 207–210 °C; 1H NMR (400 MHz, CDCl3)
d: 7.39 (t, 1H, J = 8.0 Hz, ArH), 7.58 (dd, 1H, J1 = 8.0 Hz, J2 = 0.8 Hz, ArH), 7.85
(dd, 1H, J1 = 8.0 Hz, J2 = 0.8 Hz, ArH), 8.30 (d, 2H, J = 8.8 Hz, ArH), 8.36 (d, 2H,
J = 8.8 Hz, ArH). 13C NMR (100 MHz, CDCl3) d: 120.3, 124.3, 126.7, 127.1, 128.5,
129.0, 136.8, 138.6, 149.3, 151.1, 165.5. MS: m/z 291 (MH)+. Compound 3z: mp
193–195 °C; 1H NMR (400 MHz, CDCl3) d: 2.49 (s, 3H, CH3), 7.30 (d, 1H,
J = 8.0 Hz, ArH), 7.60 (d, 2H, J = 8.0 Hz, ArH), 7.66 (s, 1H, ArH), 7.91–7.94 (m, 3H,
ArH). 13C NMR (100 MHz, CDCl3) d: 21.5, 121.3, 122.8, 125.1, 128.0, 128.7,
132.1, 132.7, 135.2, 135.6, 152.2, 165.5. MS: m/z 304 (MH)+.
1. Lion, C. J.; Matthews, C. S.; Wells, G.; Bradshaw, T. D.; Stevens, M. F. G.;
Westwell, A. D. Bioorg. Med. Chem. Lett. 2006, 16, 5005.
2. Vicini, P.; Geronikaki, A.; Incerti, M.; Busonera, B.; Poni, G.; Cabras, C. A.; Colla,
P. L. Bioorg. Med. Chem. 2003, 11, 4785.
3. Zajac, M.; Hrobárik, P.; Magdolen, P.; Foltínová, P.; Zahradník, P. Tetrahedron
2008, 64, 10605.
4. Cressier, D.; Prouillac, C.; Hernandez, P.; Amourette, C.; Diserbo, M.; Lion, C.;
Rima, G. Bioorg. Med. Chem. 2009, 17, 5275.
5. (a) Zhang, X. H.; Wong, O. Y.; Gao, Z. Q.; Lee, C. S.; Kwong, H. L.; Lee, S. T.; Wu, S.
K. Mater. Sci. Eng. 2001, B85, 182; (b) Zhang, L.; Xu, Q. F.; Lu, J. M.; Li, N. J.; Yan,
F.; Wang, L. H. Polymer 2009, 50, 4807; (c) Bae, J. S.; Gwon, S. Y.; Son, Y. A.; Kim,
S. H. Dyes Pigments 2009, 83, 324; (d) Dutta, G. K.; Guha, S.; Patil, S. Org.
Electron. 2010, 11, 1; (e) Chen, L. Q.; Yang, C. L.; Qin, J. G. Spectrochim. Acta, Part
A 2007, 68, 317.
6. Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Heterocycles 2004, 63, 2769. and
references cited therein.
7. Kawashita, Y.; Ueba, C.; Hayashi, M. Tetrahedron Lett. 2006, 47, 4231.
8. Praveen, C.; Kumar, K. H.; Muralidharan, D.; Perumal, P. T. Tetrahedron 2008, 64,
2369.
9. Bahrami, K.; Khodaei, M. M.; Naali, F. J. Org. Chem. 2008, 73, 6835.
10. Kumar, A.; Maurya, R. A.; Saxena, D. Mol. Divers. 2009. doi:10.1007/s11030-
009-9170-8.
11. (a) Pratap, U. R.; Mali, J. R.; Jawale, D. V.; Mane, R. A. Tetrahedron Lett. 2009, 50,
1352; (b) Xiao, H. L.; Chen, J. X.; Liu, M. C.; Zhu, D. J.; Ding, J. C.; Wu, H. Y. Chem.
Lett. 2009, 38, 170.
25. Peyron, C.; Benhida, R.; Bories, C.; Loiseau, P. M. Bioorg. Chem. 2005, 33, 439.
26. Ono, A.; Okamoto, T.; Inada, M.; Nara, H.; Matsuda, A. Chem. Pharm. Bull.
(Tokyo) 1994, 42, 2231.
27. Typical procedure for the preparation of 5a: A mixture containing 30,50-diacetyl-
5-formyl-20-deoxyuridine (1 mmol), o-aminobenzenethiol (2, 1 mmol), and
RuCl3 (0.05 mmol) in [bmim]PF6 (1 mL) was stirred at 80 °C for 2 h. Upon
completion, the crude product was purified by column chromatography
eluting with hexane/ethyl acetate (20–50%) to give 5a. Details of analytical
data of selected compounds are presented as follows: Compound 5a: mp 223–
225 °C; 1H NMR (400 MHz, CDCl3) d: 2.16 (s, 3H, CH3), 2.28 (s, 3H, CH3), 2.32–
2.62 (m, 2H, CH2), 4.40–4.49 (m, 3H, CH, CH2), 5.36–5.38 (m, 1H, CH), 6.48–6.52
(m, 1H, CH), 7.38 (t, 1H, J = 7.6 Hz, ArH), 7.49 (t, 1H, J = 7.6 Hz, ArH), 7.92–7.95
(m, 2H, ArH), 9.01 (s, 1H, CH), 9.36 (s, 1H, NH). 13C NMR (100 MHz, CDCl3) d:
20.9, 21.1, 38.5, 64.2, 74.7, 83.0, 85.9, 109.4, 121.6, 122.2, 124.7, 126.3, 135.7,
139.3, 149.2, 151.8, 158.4, 160.8, 170.4, 170.6. MS: m/z 446 (MH)+. Compound
5c: mp 206–207 °C; 1H NMR (400 MHz, DMSO-d6) d: 2.15 (s, 3H, CH3), 2.50–
2.62 (m, 2H, CH2), 4.21–4.55 (m, 4H, 2 ꢀ CH, CH2), 6.13–6.18 (m, 1H, CH), 7.39
(t, 1H, J = 7.6 Hz, ArH), 7.51 (t, 1H, J = 7.6 Hz, ArH), 7.89 (d, 1H, J = 7.6 Hz, ArH),
8.09 (d, 1H, J = 7.6 Hz, ArH), 8.85 (s, 1H, CH), 12.12 (s, 1H, NH). 13C NMR
(100 MHz, DMSO-d6) d: 21.2, 37.7, 60.5, 63.6, 82.3, 86.4, 107.4, 121.9, 122.4,
124.9, 126.8, 135.2, 140.8, 149.5, 151.8, 159.9, 161.8, 170.8. MS: m/z 429
(MH)+. Compound 5d mp: 224–226 °C; 1H NMR (400 MHz, DMSO-d6) d: 2.10 (s,
3H, CH3), 2.48–2.63 (m, 2H, CH2), 4.21–4.48 (m, 4H, 2 ꢀ CH, CH2), 6.11–6.14
(m, 1H, CH), 7.40 (d, 1H, J = 8.4 Hz, ArH), 7.85 (s, 1H, ArH), 8.09 (d, 1H,
J = 8.4 Hz, ArH), 8.82 (s, 1H, CH), 12.10 (s, 1H, NH). 13C NMR (100 MHz, DMSO-
d6) d: 21.1, 37.8, 60.6, 63.6, 82.4, 86.7, 107.1, 121.2, 124.0, 124.9, 131.4, 134.0,
141.3, 149.5, 152.8, 161.9, 162.4, 170.7. MS: m/z 463 (MH)+. Compound 5i: mp:
199–202 °C; 1H NMR (400 MHz, DMSO-d6) d: 2.01 (s, 3H, CH3), 2.07 (s, 3H,
CH3), 2.48–2.50 (m, 2H, CH2), 4.26–4.38 (m, 3H, CH2, CH), 5.25 (s, 1H, CH),
6.18–6.22 (m, 1H, CH), 7.35 (t, 1H, J = 8.0 Hz, ArH), 7.55 (d, 1H, J = 8.0 Hz, ArH),
8.04 (d, 1H, J = 8.0 Hz, ArH), 8.90 (s, 1H, CH), 12.14 (s, 1H, NH). 13C NMR
(100 MHz, DMSO-d6) d: 21.1, 21.2, 38.0, 64.1, 74.7, 82.9, 87.2, 107.3, 121.4,
125.7, 126.0, 126.7, 136.9, 141.2, 148.6, 149.6, 161.2, 161.9, 170.4, 170.5. MS:
m/z 480 (MH)+.
12. Ito, S.; Aihara, K.; Matsumoto, M. Tetrahedron Lett. 1983, 24, 5249.
13. Komiya, N.; Noji, S.; Murahashi, S.-I. Chem. Commun. 2001, 65.
14. Sharma, N. K.; Ganesh, K. N. Tetrahedron Lett. 2004, 45, 1403.
15. Mashraqui, S. H.; Karnik, M. A. Tetrahedron Lett. 1998, 39, 4895.
16. Yusubov, M. S.; Chi, K.-W.; Park, J. Y.; Karimov, R.; Zhdankin, V. V. Tetrahedron
Lett. 2006, 47, 6305.
17. Sharma, V. B.; Jain, S. L.; Sain, B. Tetrahedron Lett. 2004, 45, 4281.
18. Plietker, B.; Niggemann, M. J. Org. Chem. 2005, 70, 2402.
19. Murahashi,S.-I.;Komiya,N.;Terai,H.;Nakae,T.J.Am.Chem.Soc. 2003,125,15312.
20. (a) Ranke, J.; Stolte, S.; Strörmann, R.; Arning, J.; Jastorff, B. Chem. Rev. 2007,
107, 2183; (b) Stolte, S.; Matzke, M.; Arning, J.; Böschen, A.; Pitner, W. R.; Welz-
Biermann, U.; Jastorff, B.; Ranke, R. Green Chem. 2007, 9, 1170.
21. (a) Afonso, C. A. M.; Branco, L. C.; Candeias, N. R.; Gois, P. M. P.; Lourenco, N. M.
T.; Mateus, N. M. M.; Rosa, J. N. Chem. Commun. 2007, 2669; (b) Pârvulescu, V.
I.; Hardacre, C. Chem. Rev. 2007, 107, 2615.
22. (a) Martins, M. A.; Frizzo, C. P.; Moreira, D. N.; Zanatta, N.; Bonacorso, H. G.
Chem. Rev. 2008, 108, 2015; (b) Charkraborti, A. K.; Roy, S. R. J. Am. Chem. Soc.
2009, 131, 6902.
23. (a) Fan, X.; Hu, X.; Zhang, X.; Wang, J. Aust. J. Chem. 2004, 57, 1067; (b) Fan, X.;
Hu, X.; Zhang, X.; Wang, J. Can. J. Chem. 2005, 83, 16; (c) Fan, X.; Li, Y.; Zhang,
X.; Wang, J. Can. J. Chem. 2006, 84, 794; (d) Zhang, X.; Fan, X.; Niu, H.; Wang, J.
Green Chem. 2003, 5, 267.
24. Typical procedure for the preparation of 3a: A mixture containing aldehyde (1a,
1 mmol), o-aminobenzenethiol (2a, 1 mmol), and RuCl3 (0.05 mmol) in
[bmim]PF6 (1 mL) was stirred at 80 °C for 0.5 h. Upon completion, the
mixture was extracted with diethyl ether (10 mL ꢀ 3). The combined organic
phases were washed with H2O and dried over MgSO4, filtered, and
concentrated under vacuum. The crude product was purified by column
chromatography eluting with hexane/ethyl acetate (5–20%) to give 3a. Other 2-
substituted benzothiazoles were obtained in a similar manner. Details of