Merrifield resin supported phenanthroline-Cu(I): A highly efficient and recyclable catalyst for the synthesis of 2-aminobenzothiazoles via the reaction of 2-haloanilines with isothiocyanates

Article abstract of DOI:10.1016/j.tet.2011.05.121

A novel Merrifield resin supported phenanthroline-Cu(I) complex has been developed and used as a highly efficient and recyclable catalyst in the reaction of 2-halobenzenamines with isothiocyanates for the synthesis of 2-aminobenzothiazoles. The reactions

Full text of DOI:10.1016/j.tet.2011.05.121

Tetrahedron 67 (2011) 5543e5549
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Merrifield resin supported phenanthrolineeCu(I): a highly efficient and
recyclable catalyst for the synthesis of 2-aminobenzothiazoles via the
reaction of 2-haloanilines with isothiocyanates
,b,
Jin Yang a, Pinhua Li a, Lei Wang a
*
a Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel Merrifield resin supported phenanthrolineeCu(I) complex has been developed and used as
a highly efficient and recyclable catalyst in the reaction of 2-halobenzenamines with isothiocyanates for
Received 9 April 2011
Accepted 31 May 2011
Available online 2 June 2011
the synthesis of 2-aminobenzothiazoles. The reactions were applicable to
a variety of 2-
halobenzenamines and isothiocyanates, and generated the corresponding 2-aminobenzothiazoles in
good yields under mild reaction conditions. Moreover, the catalyst was quantitatively recovered from the
reaction mixture by a simple filtration and reused for ten cycles with almost consistent activity.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
2-Aminobenzothiazoles
PhenanthrolineeCu(I) complex
Immobilized catalyst
Tandem reaction
Recyclability
1. Introduction
and agrochemicals that show prominent biological activities with
applications in drug discovery since Hugerschoff’s synthesis of
Transition-metal-catalyzed cross-coupling reactions of car-
bonecarbon and carboneheteroatom bonds are important syn-
thetic reactions in modern organic synthesis, and they have
emerged as powerful tools in both academic and industrial labo-
ratories. Among the reactions, palladium,1 copper,2 iron3 and
nickel4 catalysts combined with a ligand display high activity.
However, the drawbacks are the high prices of the complexes and
the often laborious removal of the metals from product. From in-
dustrial and environmental points of view, the development of
a cheap, efficient and environmentally benign catalyst is still de-
sirable. Therefore, the application of reusable and recoverable
heterogeneous catalysts has recently attracted much attention, for
their facile isolation and reusability, which could reduce both cost
and waste.5 In the past decades, a lot of techniques to recycle metal-
based heterogeneous catalysts have been developed, such as silica,6
ionic liquids,7 and polymers.8 The grafting of such supports with
homogeneous catalysts often provides good catalytic activity to-
gether with possible recovery of the catalyst system by simple
conduction.
2-aminobenzothiazoles through a reaction of arylthioureas with
liquid bromine.9 Synthesis of 2-aminobenzothiazoles is one of the
important topics in the preparation of heterocyclic compounds.
Therefore, considerable effort has been made in the development of
efficient strategies for their construction. The majority of efficient
methods include the transition-metal-catalyzed, particularly
palladium- or copper-, catalyzed intra-molecular cyclization of
2-bromobenzothiaoureas (Eq. 1, Scheme 1).10 Castillon and co-
ꢀ
workers reported a procedure for the synthesis of benzothiazoles
using 2-bromoarylthioamide substrates and the Pd2(dba)3/
(2-biphenyl)P(t-Bu)2 catalytic system.10c However, both a ligand
and a base are required to promote the reaction, and the substrates
are not readily available. Recently, Li and Wu’s groups described
the practical transition-metal-catalyzed tandem reactions of
2-halobenzenamines and isothiocyanates to prepare 2-amino-
benzothiozoles in the presence of CuI-phenanthroline, or FeF3
(FeCl3)-phenanthroline catalytic system (Eq. 2, Scheme 1).11
Meanwhile, CuI/K2CO3 system and CuBr/TBAB system without li-
gand were also employed as the catalyst in this transformation,
respectively (Eq. 3, Scheme 1).12
2-Aminobenzothiazoles, one of the important classes of het-
erocyclic compounds, have been found in many pharmaceuticals
Although homogeneous catalysis exhibit many advantages, ho-
mogeneous catalysis suffers from the problematic separation of the
expensive catalyst. In addition, homogeneous catalysis might result
in heavy metal contamination of the desired isolated product.
* Corresponding author. Tel.: þ86 561 380 2069; fax: þ86 561 309 0518; e-mail
address: leiwang@chnu.edu.cn (L. Wang).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.05.121

5544
J. Yang et al. / Tetrahedron 67 (2011) 5543e5549
was washed with ethanol, diethyl ether and dried in vacuum,
phenanthrolin-functionalized resin 3 was obtained, and then the
resin 3 reacted with CuI in CH3CN at room temperature for 4 h to
generate the polystyrene-immobilized phenanthroline copper
catalyst 4 as a pale-yellow powder, the copper content of the cat-
alyst was found to be 0.25 mmol gꢁ1 according to the ICP-AES
measurements.
In our initial screening experiments, the reaction between 2-
iodoaniline and phenyl isothiocyanate was investigated to opti-
mize the reaction conditions, and the results are summarized in
Table 1. At first, the solvent effect was examined, and a significant
solvent effect was observed. It is evident that high yields were
obtained when the reaction was performed in toluene, acetonitrile,
and DMF (Table 1, entries 1e3), whereas 1,4-dioxane and DCE
afforded moderate yields (Table 1, entries 4 and 5), so the toluene
was finally selected as the solvent for the reaction.
Scheme 1.
These problems are of particular environmental and economic
concern in large-scale syntheses. To overcome these problems, the
development of highly efficient and recyclable heterogeneous cat-
alysts, such as immobilization of catalytically active metal com-
plexes onto the surfaces of organic and inorganic supports is
essential.
Table 1
Reaction condition screening for the reaction of 2-iodoaniline with phenyl
isothiocyanatea
As a part of our continuing interest in the development of effi-
cient heterogeneous catalysts for the organic synthesis,13 herein we
report a recoverable and efficient Merrifield resin supported phe-
nanthrolineeCu(I) catalyst, which exhibits a high catalytic activity
in the reactions of 2-halobenzenamines with isothiocyanates for
the synthesis of 2-aminobenzothiazoles. In addition, the catalyst
could be easily recovered from the reaction mixture by a simple
filtration and reused at least 10 times without significant loss of its
catalytic activity (Scheme 2).
Entry
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
DABCO
DABCO
DABCO
DABCO
DABCO
Cs2CO3
K3PO4
Na3PO4
K2CO3
Na2CO3
NaOAc
Et3N
Toluene
DMF
CH3CN
1,4-Dioxane
DCE
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
95
92
93
72
76
42
52
48
38
32
20
38
81
9
10
11
12
13c
DABCO
a
Reaction conditions: 2-iodoaniline (0.2 mmol), phenyl isothiocyanate
(0.22 mmol), supported copper catalyst 4 (20 mg, containing Cu 0.005 mmol), base
(0.4 mmol), solvent (1.0 mL), 60 ꢀC for 8 h.
b
Isolated yields.
In the presence of supported copper catalyst
c
4 (10 mg, containing Cu
0.0025 mmol).
Our next studies focused on the effect of base on the model
reaction. Among the bases examined, it turned out that DABCO act
as an excellent base (Table 1, entry 1). While other bases, such as
Cs2CO3, Na2CO3, NaOAc, Na3PO4, K2CO3, K3PO4 and triethylamine
were substantially less effective (Table 1, entries 6e12). The effect of
reaction temperature and time on the reaction was also in-
vestigated. It was found that the reaction was accomplished when it
was carried out at 60 ꢀC for 8 h. The amount of supported copper
catalyst was also screened, and 2.5 mol % loading of copper was
found to be optimal, a lower yield was observed when the amount
of catalyst was decreased (Table 1, entry 13).
With this promising result in hand, we started to investigate the
scope of this reaction under the optimized conditions. The scope of
both 2-haloanilines and isothiocyanates was explored, and the re-
sults are summarized in Table 2. At the beginning of the de-
termination of the 2-haloanilines substrate scope, phenyl
isothiocyanate was used as one of the model substrate. The stan-
dard conditions were also successfully applied in the reactions of
both 2-bromoaniline and 2-chloroaniline (Table 2, entries 2 and 3).
For example, 2-bromoaniline underwent the reaction with phenyl
isothiocyanate smoothly and generated the corresponding product
in 94% yield, in addition, the reaction of the inactive 2-chloroaniline
with the phenyl isothiocyanate also gave a moderate yield. Sub-
sequently various 2-bromoanilines containing both electron-
Scheme 2.
2. Results and discussion
The polystyrene-immobilized phenanthroline copper catalyst
(4) was easily prepared starting from the commercially available
Merrifield resin according to Scheme 2. Firstly, Merrifield resin
reacted with 4-hydroxybenzaldehyde in the presence of sodium
hydride in anhydrous DMF in 90 ꢀC for 6 h to generate function-
alized resin 1. The above functionalized resin 1 was subsequently
treated with 5-amine-1,10-phenanthrolin (2) in ethanol under
reflux condition for 24 h. After the organics were filtered, the resin

J. Yang et al. / Tetrahedron 67 (2011) 5543e5549
5545
Table 2
Merrifield resin supported phenanthrolineeCu(I) (4)-catalyzed reactions of 2-halobenzenamines (5) with isothiocyanates (6)a
Entry
1
Halobenzenamines
Isothiocyanates
Product
Yield [%]b
7a
95
94
2
3
4
7a
7a
7b
52
88
5
6
7c
86
71
7d
7
7e
84
8
7f
7g
7h
7i
90
88
98
92
90
86
78
9
10
11
12
13
14
7j
7k
7l
15
7m
89
16
17
7n
7o
84
88
(continued on next page)

5546
J. Yang et al. / Tetrahedron 67 (2011) 5543e5549
Table 2 (continued )
Entry
Halobenzenamines
Isothiocyanates
Product
Yield [%]b
18
7p
69
19
20
7q
7r
78
85
21
7s
75
a
Reaction conditions: 2-halobenzenamine (0.2 mmol), isothiocyanate (0.22 mmol), supported copper catalyst 4 (20 mg, containing Cu 0.005 mmol), and DABCO (0.4 mmol),
toluene (1.0 mL), 60 ꢀC for 8 h.
b
Isolated yields.
donating and electron-withdrawing groups, such as methyl, fluoro,
bromo and trifluoromethyl groups on the benzene rings 5deg were
investigated to react with isothiocyanates under the standard
conditions. As showed in Table 2, generally the reactions proceeded
successfully to afford the corresponding 2-aminobenzothiazoles in
moderate to excellent yields. For example, reaction of 2-bromo-4-
methylaniline (5d) with phenyl isothiocyanate afforded the de-
sired product 7b in 88% yield (Table 2, entry 4). A similar result (86%
yield) was obtained for the reaction of 2,4-dibromoaniline (5e)
with phenyl isothiocyanate (Table 2, entry 5). In addition, a less
active substrate, such as 2-bromo-5-trifluoromethylaniline (5f),
also displayed high activity for the tandem reaction with phenyl
isothiocyanate in 71% yield (Table 2, entry 6). Finally, it should be
worth noting that for the hindered 2,4-dibromo-6-fluoroaniline
(5h), a good yield was also obtained (Table 2, entry 7).
recyclability of the polystyrene-immobilized phenanthrolineeCu(I)
catalyst 4 was also investigated. After carrying out the reaction, the
catalyst was separated by simple filtration and washed with diethyl
ether (2ꢂ2.5 mL). After being air-dried, it can be reused directly
without further purification. The recovered catalyst was used in the
next run, and almost consistent activity was observed for ten
consecutive cycles (Table 3, entries 1e10). In addition, copper
leaching in the supported catalyst was also determined. ICP anal-
ysis of the clear filtrates found that Cu content less than 0.20 ppm.
Table 3
Successive runs by using recovered polystyrene-immobilized phenanthrolineeCu(I)
catalyst 4a
Encouraged by the above results, the scope and the generality of
the reaction by varying the isothiocyanates were further in-
vestigated. We were pleased to find that the standard conditions
were compatible with various isothiocyanates 6bei bearing
methoxy, chloro, methyl, nitro and trifluoromethyl groups. It was
found that both electron-rich and electron-poor aryl iso-
thiocyanates underwent the tandem reaction efficiently and gen-
erated the corresponding products in good to excellent yields. For
example, substrate 6b and 6c with 4-methoxy and 4-chloro groups
on phenyl isothiocyanate underwent the reaction with
2-bromoaniline (5b), smoothly and the desired products were
isolated in good yields (Table 2, entries 8 and 9). Meanwhile, almost
quantitative yield of 2-aminobenzothiazole 7h was obtained when
4-nitrophenyl isothiocyanate (6d) was used as a replacement (Table
2, entry 10). 4-Methylphenyl isothiocyanate (6e), was treated with
2-bromoaniline (5b) to afford the target product 7i in 92% yield
(Table 2, entry 11), and 3-methylphenyl isothiocyanate (6f) pro-
vided the corresponding product 7j in 90% yield (Table 2, entry 12).
Substrate 6g, bearing a 2-methylphenyl group, could also react with
2-bromoaniline (5b) smoothly and the product was isolated in 86%
yield (Table 2, entry 13). On the other hand, the reactions of
2-bromoaniline with substituted groups, such as methyl, and
bromo groups on the benzene rings with various substituted iso-
thiocyanates, afforded the corresponding products also in good
yields (Table 2, entries 16e21).
Cycle
Yield [%]b
Cycle
Yield [%]b
1
3
5
7
9
95
93
91
88
86
2
4
6
8
10
95
92
90
87
86
a
Reaction conditions: 2-iodoaniline (00.2 mmol), phenyl isothiocyanate
(0.22 mmol), DABCO (0.4 mmol), supported copper catalyst 4 (2.5 mol %), toluene
(1.0 mL), nitrogen, 60 ꢀC for 8 h.
b
Isolated yields.
3. Conclusion
In summary, we have successfully developed a novel, practical
and environmentally friendly method for the synthesis of 2-
aminobenzothiazoles through the reaction of 2-halobenzenamines
with isothiocyanates by using polystyrene-immobilized phenan-
throlineeCu(I) 4 as catalyst (2.5 mol %) under mild reaction condi-
tions. The reactions generated the corresponding 2-
aminobenzothiazoles in high yields and were applicable to various
2-halobenzenamines and isothiocyanates. In addition, this meth-
odology offers the competitiveness of recyclability of the catalyst
without significant loss of catalytic activity, and the catalyst could be
readily recovered and reused for 10 cycles, thus making this pro-
cedure environmentally more acceptable.
For a heterogeneous catalyst, it is important to examine its ease
of separation, good of recoverability and reusability. The

J. Yang et al. / Tetrahedron 67 (2011) 5543e5549
5547
4. Experimental
catalyst. As supported catalyst 4 was precipitated to the bottom of
the flask, the organic layer was decanted and the residue was
washed with Et2O (2ꢂ5.0 mL). The combined organic layers were
concentrated, and then the residue was purified by flash chroma-
tography on silica gel to provide the corresponding pure product 7a
in 95% yield.
4.1. Physical measurements and materials
General: all 1H and 13C NMR spectra were recorded with
a Bruker Avance NMR spectrometer (400 MHz or 100 MHz, re-
spectively). Chemical shifts are given as
d value with reference to
tetramethylsilane (TMS) as the internal standard. The C, H and N
analyses were performed with a Vario El III elementar. The Cu
content was determined with a Jarrell-Ash 1100 ICP analysis. 5-
amine-1,10-phenanthrolin (2) was prepared according to the liter-
ature.14 Products were purified by flash column chromatography on
230e400 mesh silica gel, SiO2.
4.5.1. N-Phenylbenzo[d]thiazol-2-amine (7a). White solid, mp
158e159 ꢀC (lit.11a mp 158.1e159.3 ꢀC). 1H NMR (400 MHz, CDCl3):
d
¼7.63 (d, J¼7.6 Hz, 2H), 7.51 (d, J¼7.6 Hz, 2H), 7.41 (t, J¼7.6 Hz, 2H),
7.34 (t, J¼7.6 Hz, 1H), 7.14e7.18 (m, 2H). 13C NMR (100 MHz, CDCl3):
d¼164.8, 151.3, 139.9, 129.6, 129.3, 126.1, 124.4, 122.4, 120.8, 120.3,
119.3. IR (KBr, cmꢁ1): 3212, 3074, 2930, 2869,1629,1610,1581,1480,
1457, 1448, 1386, 1319, 1270, 1177, 1122.
4.2. Preparation of benzaldehyde functionalized resin 1
4.5.2. 6-Methyl-N-phenylbenzo[d]thiazol-2-amine
(7b). White
Into a 100-mL round-bottom flask were introduced successively
anhydrous DMF (40.0 mL), 4-hydroxybenzaldehyde (1.17 g) and
sodium hydride (0.44 g). After the solution was stirred at room
temperature for 2 h, the Merrifield resin (4.0 g) was added and the
solution was refluxed in 90 ꢀC for 6 h. The solution was filtered, and
the solid was washed subsequently with DMF (5.0 mL), dichloro-
methane (5.0 mL), diethyl ether (5.0 mL) and dried under reduced
pressure to yield 4.4 g of benzaldehyde functionalized resin 1. IR
solid, mp 157e159 ꢀC (lit.12a mp 157e160 ꢀC). 1H NMR (400 MHz,
CDCl3):
d
¼8.80 (s, 1H), 7.51e7.47 (m, 3H), 7.45 (s, 1H), 7.41 (t,
J¼8.0 Hz, 2H), 7.14e7.19 (m, 2H), 2.43 (s, 3H). 13C NMR (100 MHz,
CDCl3):
d¼164.1, 149.1, 140.0, 132.2, 129.9, 129.5, 127.4, 124.1, 120.9,
120.1, 118.9, 21.3. IR (KBr, cmꢁ1): 3216, 2871, 1631, 1611, 1580, 1482,
1458, 1450, 1388, 1320, 1272, 1174, 1125.
4.5.3. 6-Bromo-N-phenylbenzo[d]thiazol-2-amine
(7c). White
¼10.57 (s,
(KBr, cmꢁ1): 3436, 3057, 3024, 2919, 2849, 1671 (
1492, 1419, 1384, 1250, 1157, 1066, 1017.
n
C]O), 1599, 1508,
solid, mp 185e187 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d
1H), 8.04 (s, 1H), 7.76 (d, J¼8.0 Hz, 2H), 7.51 (d, J¼8.4 Hz, 1H),
7.44 (d, J¼8.4 Hz, 1H), 7.36 (t, J¼8.0 Hz, 2H), 7.02 (t, J¼8.0 Hz,
4.3. Preparation of phenanthroline functionalized resin 3
1H). 13C NMR (100 MHz, DMSO-d6):
d
¼162.7, 151.8, 140.8, 132.6,
129.5, 129.2, 124.0, 122.8, 121.1, 118.3, 114.2. IR (KBr, cmꢁ1): 3214,
3077, 2870, 1632, 1612, 1580, 1484, 1458, 1453, 1389, 1320, 1273,
1175, 1128. HRMS (ESI): calcd for C13H9BrN2S [M]þ 303.9670;
found 303.9671.
5-Amine-1,10-phenanthrolin (2) (0.41 g, 5.0 mmol) and benz-
aldehyde functionalized resin 1 (2.0 g) were mixed in ethanol
(25.0 mL) in a round-bottom flask. The reaction was carried out at
80 ꢀC for 24 h. Then the solution was filtered, and the solid was
washed with ethanol (5.0 mL), diethyl ether (5.0 mL), and dried
under vacuum to yield 2.08 g of phenanthroline functionalized
resin 3 as a yellow powder. The loading of the phenanthroline
functionalized resin 3 was quantified by CHN microanalysis and
found to be 0.76 mmol gꢁ1 based on the N content. IR (KBr, cmꢁ1):
4.5.4. 5-Trifluoromethyl-N-phenylbenzo[d]thiazol-2-amine
(7d). White solid; mp 199e200 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d
¼10.77 (s, 1H), 8.03 (d, J¼8.0 Hz, 1H), 7.87 (s, 1H), 7.79 (d, J¼8.0 Hz,
2H), 7.45 (d, J¼8.4 Hz, 1H), 7.37 (t, J¼8.0 Hz, 2H), 7.05 (t, J¼7.2 Hz,
1H). 13C NMR (100 MHz, DMSO-d6):
d¼163.8, 152.6, 140.7, 135.0,
3057, 3023, 2918, 1601 (
n
C]O), 1573, 1507, 1492, 1451, 1419, 1374,
129.5, 127.1, 125.0 (q, 1JCF¼270.4 Hz), 122.8 (q, 2JCF¼44.1 Hz), 118.8,
118.7, 118.5, 115.7. IR (KBr, cmꢁ1): 3198, 2958, 1627, 1572, 1467, 1458,
1426, 1329, 1308, 1148, 1112. HRMS (ESI): calcd for C14H9F3N2S [M]þ
294.0439; found 294.0440.
1300, 1221, 1163, 1109, 1002.
4.4. Preparation of the polystyrene-immobilized
phenanthrolineeCu(I) catalyst 4
4.5.5. 6-Bromo-4-fluoro-N-phenylbenzo[d]thiazol-2-amine
(7e). White solid, mp 194e196 ꢀC. 1H NMR (400 MHz, DMSO-d6):
In an oven-dried Schlenk flask, freshly prepared CuI (0.190 g,
1.0 mmol), phenanthroline functionalized resin 3 (1.0 g) and CH3CN
(5.0 mL) were added. The resulting suspension was stirred at room
temperature under nitrogen for 6 h. Then the solution was filtered,
and the solid was washed with CH3CN (5.0 mL), diethyl ether
(5.0 mL) and dried under vacuum. The polystyrene-immobilized
phenanthrolineeCu(I) catalyst 4 was obtained as a yellow powder
(1.06 g). The copper content of the catalyst was found to be
0.25 mmol gꢁ1 based on ICP analysis. IR (KBr, cmꢁ1): 3081, 3057,
d
¼10.77 (s, 1H), 7.89 (s, 1H), 7.75 (d, J¼8.0 Hz, 2H), 7.45 (d,
J¼10.4 Hz, 1H), 7.37 (t, J¼8.0 Hz, 2H), 7.95 (t, J¼7.6 Hz, 1H). 13C NMR
(100 MHz, DMSO-d6):
d
¼163.1, 152.5 (d, 1JCF¼252.1 Hz), 140.5, 140.0
3
2
(d, JCF¼12.5 Hz), 134.7, 129.5, 120.4, 118.5, 115.9 (d, JCF¼21.4 Hz),
118.8,113.2. IR (KBr, cmꢁ1): 3259, 3200, 3075,1613,1561,1527,1496,
1446, 1316, 1278, 1243, 1191. HRMS (ESI): calcd for C13H8BrFN2S
[M]þ 321.9576; found 321.9578.
3023, 2919, 2849, 1675 (
1244, 1165, 1017.
n
C]O), 1601, 1508, 1492, 1419, 1392, 1302,
4.5.6. N-(4-Methoxyphenyl)benzo[d]thiazol-2-amine
solid, mp 154e156 ꢀC (lit.11a mp 154.4e155.8 ꢀC). 1H NMR
(400 MHz, CDCl3):
¼7.59 (d, J¼7.6 Hz, 1H), 7.44e7.42 (m, 3H), 7.28
(t, J¼7.6 Hz, 1H), 7.11 (t, J¼7.6 Hz, 1H), 6.98 (d, J¼8.8 Hz, 2H), 3.87 (s,
(7f). White
d
4.5. Typical experimental procedure for synthesis
of 2-aminobenzothiazole
3H). 13C NMR (100 MHz, CDCl3):
d
¼167.5, 157.4, 151.6, 133.0, 129.7,
126.0, 124.3, 121.8, 120.8, 118.7, 114.8, 55.5. IR (KBr, cmꢁ1): 3201,
2957, 1629, 1577, 1472, 1453, 1420, 1321, 1300, 1142, 1112.
A mixture of 2-iodoaniline (0.20 mmol), phenyl isothiocyanate
(0.22 mmol), DABCO (0.40 mmol, 2.0 equiv) and polystyrene-
immobilized phenanthrolineeCu(I) catalyst 4 (20 mg, containing
Cu 0.005 mmol) and toluene (1.0 mL) was stirred at 60 ꢀC for 8 h.
After completion of the reaction as indicated by TLC, the mixture
was cooled to room temperature and Et2O (5.0 mL) was added and
the mixture stirred for 10 min to ensure product removal from
4.5.7. N-(4-Chlorophenyl)benzo[d]thiazol-2-amine
solid, mp 203e205 ꢀC (lit.11a mp 204.2e206.5 ꢀC). 1H NMR
(400 MHz, DMSO-d6):
¼10.61 (s, 1H), 7.83e7.81 (m, 3H), 7.61
(7g). White
d
(d, J¼7.2 Hz, 1H), 7.40 (d, J¼8.0 Hz, 2H), 7.32 (t, J¼7.2 Hz, 1H), 7.16
(t, J¼7.2 Hz, 1H). 13C NMR (100 MHz, DMSO-d6):
¼161.7, 152.4,
d

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J. Yang et al. / Tetrahedron 67 (2011) 5543e5549
140.0, 130.4, 129.3, 126.4, 125.8, 122.9, 121.6, 119.8, 119.6. IR
(KBr, cmꢁ1): 3199, 2960, 1625, 1574, 1470, 1454, 1422, 1325, 1300,
1145, 1110.
114.6, 55.6, 21.3. IR (KBr, cmꢁ1): 3177, 2930, 1611, 1573, 1555, 1511,
1462, 1450, 1268, 1246, 1182, 1166, 1034.
4.5.15. N-(4-Chlorophenyl)-6-methylbenzo[d]thiazol-2-amine
4.5.8. N-(4-Nitrophenyl)benzo[d]thiazol-2-amine (7h). Yellow solid,
mp 224e227 ꢀC (lit.11a mp 225.2e227.2 ꢀC). 1H NMR (400 MHz,
(7o). White solid, mp 196e197 ꢀC (lit.12a mp 197 ꢀC). 1H NMR
(400 MHz, DMSO-d6):
1H), 7.49 (d, J¼8.0 Hz, 1H), 7.38 (d, J¼8.8 Hz, 2H), 7.13 (d, J¼8.0 Hz,
1H), 2.35 (s, 3H). 13C NMR (100 MHz, DMSO-d6):
d
¼10.50 (s, 1H), 7.80 (d, J¼8.4 Hz, 2H), 7.59 (s,
DMSO-d6):
d
¼11.22 (s, 1H), 8.26 (d, J¼8.8 Hz, 2H), 8.00 (d, J¼8.8 Hz,
2H), 7.88 (d, J¼8.0 Hz, 1H), 7.71 (d, J¼8.0 Hz, 1H), 7.39 (t, J¼8.0 Hz,
d
¼160.9, 140.1,
1H), 7.24 (d, J¼7.6 Hz, 1H). 13C NMR (100 MHz, DMSO-d6):
d
¼161.1,
132.3, 130.5, 129.3, 129.3, 127.5, 127.5, 125.6, 121.4, 119.5, 21.3. IR
(KBr, cmꢁ1): 3165, 2943, 1618, 1577, 1559, 1521, 1452, 1366, 1320,
1265, 1241, 1185, 1146, 1114.
151.9, 146.9, 141.3, 130.8, 126.7, 125.9, 123.7, 121.8, 120.5, 117.6. IR
(KBr, cmꢁ1): 3337, 1612, 1592, 1569, 1533, 1497, 1489, 1318, 1302,
1288, 1256, 1247, 1170, 1161, 1145, 1112.
4.5.16. 6-Methyl-N-(4-nitrophenyl)benzo[d]thiazol-2-amine
4.5.9. N-(p-Tolyl)benzo[d]thiazol-2-amine (7i). White solid, mp
177e178 ꢀC (lit.11a mp 177.0e177.5 ꢀC). 1H NMR (400 MHz, DMSO-
(7p)11c. Yellow solid, mp 265e267 ꢀC. 1H NMR (400 MHz, DMSO-
d6):
d
¼11.09 (br s, 1H), 8.23 (d, J¼8.8 Hz, 2H), 7.97 (d, J¼9.2 Hz, 2H),
d6):
7.56 (d, J¼7.6 Hz, 1H), 7.30 (t, J¼7.6 Hz, 1H), 7.16e7.10 (m, 3H), 2.26
(s, 3H). 13C NMR (100 MHz, DMSO-d6):
d¼10.36 (s, 1H), 7.77 (d, J¼7.6 Hz, 1H), 7.65 (d, J¼8.0 Hz, 2H),
7.65 (s, 1H), 7.58 (d, J¼8.4 Hz, 1H), 7.18 (t, J¼8.0 Hz, 1H), 2.37 (s, 3H).
13C NMR (100 MHz, DMSO-d6):
d¼160.2, 149.9, 146.7, 141.2, 133.1,
d
¼162.1, 152.6, 138.7,
130.8,127.8,125.9,121.6,120.1,117.4, 21.4. IR (KBr, cmꢁ1): 3317,1610,
1595, 1574, 1540, 1498, 1484, 1325, 1304, 1260, 1181, 1155, 1111.
131.4, 130.4, 129.8, 126.3, 122.5, 121.4, 119.5, 118.3, 20.9. IR (KBr,
cmꢁ1): 3215, 2959, 1628, 1598, 1573, 1478, 1328, 1300, 1286, 1253,
1172, 1110.
4.5.17. 6-Bromo-N-(4-methoxyphenyl)benzo[d]thiazol-2-amine
(7q). White solid, mp 207e209 ꢀC. 1H NMR (400 MHz, DMSO-d6):
4.5.10. N-(m-Tolyl)benzo[d]thiazol-2-amine (7j)12a. White solid, mp
d
¼10.35 (s, 1H), 8.00 (s, 1H), 7.64 (d, J¼8.8 Hz, 2H), 7.43 (d, J¼6.8 Hz,
116e117 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d
¼10.41 (s, 1H), 7.78 (d,
2H), 6.94 (d, J¼8.8 Hz, 2H), 3.73 (s, 3H). 13C NMR (100 MHz, DMSO-
J¼7.6 Hz, 1H), 7.65e7.56 (m, 3H), 7.31 (t, J¼8.0 Hz, 1H), 7.23 (t,
d6):
d¼163.2, 155.3, 152.0, 134.1, 132.6, 129.1, 123.9, 120.7, 120.3,
J¼7.6 Hz, 1H), 7.13 (t, J¼7.6 Hz, 1H), 6.83 (d, J¼7.2 Hz, 1H), 2.31 (s,
114.7, 113.8, 55.7. IR (KBr, cmꢁ1): 3327, 1615, 1598, 1577, 1544, 1500,
1485, 1325, 1300, 1257, 1183, 1165, 1114. HRMS (ESI): calcd for
C14H11BrN2OS [M]þ 333.9775; found 333.9778.
3H). 13C NMR (100 MHz, DMSO-d6):
130.4, 129.3, 126.3, 123.3, 122.7, 121.4, 119.6, 118.7, 115.5, 21.8. IR
(KBr, cmꢁ1): 3200, 1629, 1599, 1560, 1515, 1467, 1415, 1400, 1355,
1341, 1294, 1255, 1066.
d
¼162.1, 152.6, 141.0, 138.7,
4.5.18. 6-Bromo-N-(p-tolyl)benzo[d]thiazol-2-amine
(7r). White
¼10.47 (s,
solid, mp 202e203 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d
4.5.11. N-(o-Tolyl)benzo[d]thiazol-2-amine (7k). White solid, mp
121e123 ꢀC (lit.11a mp 121.1e123.2 ꢀC). 1H NMR (400 MHz, DMSO-
1H), 8.03 (s, 1H), 7.62 (d, J¼8.4 Hz, 2H), 7.48 (d, J¼8.8 Hz, 1H), 7.42
(d, J¼8.4 Hz, 1H), 7.15 (d, J¼8.0 Hz, 2H), 2.26 (s, 3H). 13C NMR
d6):
(d, J¼8.0 Hz, 1H), 7.29e7.21 (m, 3H), 7.11e7.06 (m, 2H), 2.29 (s, 3H).
13C NMR (100 MHz, DMSO-d6):
d¼9.66 (s, 1H), 7.86 (d, J¼8.0 Hz, 1H), 7.73 (d, J¼7.6 Hz, 1H), 7.48
(100 MHz, DMSO-d6):
d
¼162.8, 151.9, 138.4, 132.6, 131.8, 129.9,
129.2, 123.9, 120.9, 118.5, 114.0, 20.9. IR (KBr, cmꢁ1): 3232, 3182,
2917, 1624, 1613, 1585, 1568, 1552, 1445, 1401, 1334, 1258, 1244,
1226, 1085. HRMS (ESI): calcd for C14H11BrN2S [M]þ 317.9826;
found 317.9828.
d
¼164.6, 152.4, 139.2, 131.2, 130.9,
130.8, 127.0, 126.2, 125.0, 123.5, 122.2, 121.5, 119.1, 18.5. IR (KBr,
cmꢁ1): 3210, 2958, 1625, 1594, 1571, 1477, 1455, 1325, 1302, 1288,
1256, 1170, 1145, 1111.
4.5.19. 6-Bromo-N-(o-tolyl)benzo[d]thiazol-2-amine
(7s). White
¼9.76 (s,1H),
4.5.12. N-(2,4-Dimethoxyphenyl)benzo[d]thiazol-2-amine
solid, mp 198e199 ꢀC. 1H NMR (400 MHz, DMSO-d6):
d
(7l). White solid, mp 120e121 ꢀC. 1H NMR (400 MHz, CDCl3):
7.98 (s, 1H), 7.81 (d, J¼8.0 Hz, 1H), 7.39e7.37 (m, 2H), 7.26e7.21 (m,
d
¼8.10 (s, 1H), 7.89 (br s, 1H), 7.72 (d, J¼7.6 Hz, 1H), 7.67 (d,
2H), 7.09 (t, J¼7.2 Hz, 1H), 2.27 (s, 3H). 13C NMR (100 MHz, DMSO-
J¼7.2 Hz, 1H), 7.38 (t, J¼6.8 Hz, 1H), 7.19 (t, J¼6.8 Hz, 1H), 6.82
d6):
d
¼165.4, 151.7, 138.9, 132.9, 131.2, 131.1, 129.1, 127.0, 125.4,
(d, J¼8.4 Hz, 1H), 6.55 (d, J¼7.2 Hz, 1H), 3.86 (br, s, 6H). 13C
123.9, 123.7, 120.6, 113.6, 18.4. IR (KBr, cmꢁ1): 3178, 3063, 2850,
1615, 1595, 1563, 1494, 1445, 1328, 1295, 1260, 1188, 1110, 1080,
1044. HRMS (ESI): calcd for C14H11BrN2S [M]þ 317.9826; found
317.9828.
NMR (100 MHz, CDCl3):
d¼161.7, 154.1, 152.0, 141.9, 130.4, 130.1,
126.1, 122.7, 120.7, 120.1, 110.7, 106.2, 105.0, 56.3, 55.8. IR (KBr,
cmꢁ1): 3205, 2965, 1634, 1569, 1475, 1451, 1422, 1319, 1298, 1145,
1114. HRMS (ESI): calcd for C15H14N2O2S [M]þ 286.0776; found
286.0779.
Acknowledgements
4.5.13. N-(3,5-Ditrifluoromethylphenyl)benzo[d]thiazol-2-amine
(7m)11b. White solid, mp 117e779 ꢀC. 1H NMR (400 MHz, CDCl3):
We gratefully acknowledge financial support by the National
Natural Science Foundation of China (No. 20972057, 20772043).
d
¼8.06 (s, 2H), 7.68 (d, J¼8.0 Hz, 2H), 7.58 (s, 1H), 7.40 (t,
J¼7.2 Hz, 1H), 7.25 (t, J¼7.6 Hz, 1H). 13C NMR (100 MHz, CDCl3):
Supplementary data
2
d¼161.9, 150.5, 141.5, 132.8 (q, JCF¼33.3 Hz), 129.7, 126.6,
1
124.4, 123.6 (q, JCF¼271.1 Hz), 121.1, 120.0, 118.5, 116.6. IR (KBr,
cmꢁ1): 3210, 2968, 1637, 1561, 1478, 1455, 1424, 1320, 1300, 1148,
1112.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.05.121.
References and notes
4.5.14. N-(4-Methoxyphenyl)-6-methylbenzo[d]thiazol-2-amine
(7n). White solid, mp 160e161 ꢀC (lit.12a mp 160 ꢀC). 1H NMR
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