Synthesis of 2-arylbenzothiazole derivatives based on activated carbon/oxygen oxidation followed by Suzuki-Miyaura coupling

Article abstract of DOI:10.1055/s-0031-1289772

A variety of 2-arylbenzothiazole derivatives were synthesized by the reaction of 2-aminobenzenethiol with substituted benzaldehydes in the presence of activated carbon and molecular oxygen system followed by Suzuki-Miyaura coupling using 2-phenylimidazole

Full text of DOI:10.1055/s-0031-1289772

PAPER
▌2209
paper
Synthesis of 2-Arylbenzothiazole Derivatives Based on Activated
Carbon/Oxygen Oxidation Followed by Suzuki–Miyaura Coupling
Synthesis of 2-Arylbenzothiazole Derivatives
Vasudevan Dhayalan, Masahiko Hayashi*
Department of Chemistry, Graduate School of Science, Kobe University, Nada, Kobe, 657-8501, Japan
Fax +81(78)8035688; E-mail: mhayashi@kobe-u.ac.jp
Received: 23.03.2012; Accepted after revision: 01.05.2012
50 °C for 24 hours was examined first. As shown in
Scheme 1, 2-arylbenzothiazoles 3a–e were obtained in
84–97% yield.
Abstract: A variety of 2-arylbenzothiazole derivatives were syn-
thesized by the reaction of 2-aminobenzenethiol with substituted
benzaldehydes in the presence of activated carbon and molecular
oxygen system followed by Suzuki–Miyaura coupling using 2-phe-
nylimidazole–PdCl2 complex.
On the other hand, we have interest in cross-coupling
reactions catalyzed by nitrogen-based ligand metal
complexes. For example, we have reported 2-phenylimid-
azole–PdCl2 and 2-phenylimidazoline–PdCl2 complex
catalyzed Mizoroki–Heck and Suzuki–Miyaura coupling
reactions. In these reactions, 2-phenylimidazoline–PdCl2
complex was found to exhibit higher reactivity than 2-
phenylimidazole–PdCl2 complex.18 Thus, the reaction of
the halogenated 2-arylbenzothiazoles 3a–e with several
boronic acids A__I was examined (Figure 1). The reaction
proceeded in the presence of 0.5 mol% of PdCl2 and 1
mol% of 2-phenylimidazole at 120 °C for 20–30 hours to
afforded the coupling product in 76–98% yield (Table 1).
Key words: 2-arylbenzothiazole, activated carbon, molecular oxy-
gen, Suzuki–Miyaura coupling, 2-phenylimidazole
2-Arylbenzothiazoles, -benzimidazoles and -benzothia-
zoles are a remarkably important class of biologically ac-
tive compounds. Among these, 2-arylbenzothiazoles and
their derivatives have attracted much attention in the field
of pharmaceuticals, such as antitumor,1 antimicrobial,2
anti-inflammatory,3 anticonvulsant,4 anticancer,5 antifun-
gal,6 antipsychotic,7 diuretic,8 schictosomicidal,9 anthel-
mintic,10 and antidiabetic.11,12 Furthermore, recently, 2-
hetero/aryl-substituted benzothiazoles have been investi-
gated as materials due to their solvatochromic and fluores-
cence properties,13 organic light-emitting diodes
(OLEDs),14 nonlinear optical (NLO) properties, and so
on.15,16
B(OH)2
B(OH)2
B(OH)2
B(OH)2 B(OH)2
OMe
A
B
C
D
E
Here, we report on the synthesis of a variety of 2-arylben-
zothiazole derivatives by the reaction of 2-aminobenzene-
thiol with substituted benzaldehydes in the presence of
activated carbon and molecular oxygen system17 followed
by Suzuki–Miyaura coupling catalyzed by 2-phenylimid-
azole–PdCl2 complex.18
B(OH)2
B(OH)2
(HO)2B
B(OH)2
S
N
H
OMe
OMe
NO2
The reaction of 2-aminobenzenethiol (1) with halogenat-
ed benzaldehydes 2a–e in the presence of 100 weight% of
activated carbon under oxygen atmosphere in xylene at
F
G
H
I
Figure 1 Boronic acids A–I used for coupling reactions
O2
SH
X
X
S
N
100 wt% activated carbon
+
OHC
xylene, 50 °C, 24 h
NH2
1a
2a–e
3a–e
2a X = 3-Br
2b X = 3,5-Br2
2c X = 3-I
2d X = 4-Br
2e X = 4-I
3a X = 3-Br (97%)
3b X = 3,5-Br2 (88%)
3c X = 3-I (90%)
3d X = 4-Br (84%)
3e X = 4-I (90%)
Scheme 1 Direct synthesis of 2-arylbenzothiazoles
SYNTHESIS 2012, 44, 2209–2216
Advanced online publication: 14.06.2012
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0031-1289772; Art ID: SS-2012-F0295-OP
© Georg Thieme Verlag Stuttgart · New York

2210
V. Dhayalan, M. Hayashi
PAPER
The structure of PdCl2 and 2-phenylimidazole complex Compared with the previous methods to obtain the 2-aryl-
was confirmed by single-crystal X-ray diffractometry benzothiazoles, such as H2O2/CAN,20 methanesufonic
(XRD) study (Scheme 2).19
acid/SiO2,21 or the condensation of 2-aminobenzenthiol
with S-methylthiamidinium salt in the presence of hexa-
decacyltrimethylammonium bromide (HTAB),22,23 the
present method is straightforward and gave much higher
yield.
PdCl2
Cl
Pd
Cl
+
HN
H
N
In summary, a variety of 2-arylbenzothiazole derivatives
were synthesized by the reaction of 2-aminobenzenethiol
with substituted benzaldehydes in the presence of activat-
ed carbon and molecular oxygen system followed by Su-
zuki–Miyaura coupling using 2-phenylimidazole–PdCl2
complex. In all steps, operation was simple and chemical
yields were high to excellent.
N
N
NH
·2DMF
DMF
N
Scheme 2 Synthesis of 2-phenylimidazole–PdCl2 complex
Table 1 Suzuki–Miyaura Cross-Coupling Reaction of 2-(3/4/5-Halophenyl)benzothiazole 3a–e Using 2-Phenylimidazole–PdCl2 Catalysta
PdCl2 (0.5 mol%)
2-phenylimidazole (1.0 mol%)
Ar
X
S
S
N
Aryl
Aryl
+
Ar-B(OH)2
K2CO3 (2 equiv), DMF
120 °C, 20–30 h
N
3a–e
A–I
4aA–dI, 4eG
Ar = aryl/heteroaryl
Entry
1
Product
Yield (%)b
Entry
10
Product
Yield (%)b
S
N
S
N
94 (from 3a)c
96 (from 3c)c
R
R
4aA; R = phenyl
4cF; R = 3,4-dimethoxy phenyl
S
S
N
N
2
3
4
98 (from 3a)d
76 (from 3a)c
11
12
13
98 (from 3c)c
98 (from 3c)e
R
R
R
4aB; R = 1-naphthyl
4cG; R = 2-thienyl
S
S
N
N
R
4aC; R = 2,4,6-trimethylphenyl
4cH; R = 5-indolyl
S
S
80 (from 3d)f
95 (from 3e)c
N
N
92 (from 3a)c
88 (from 3b)h
R
4dA
4eA
4aD; R = 4-anisyl
R
S
N
S
OMe
5g
14
15
96 (from 3d)i
N
R
4dD
4bA; R = phenyl
R
S
N
S
N
Me
86 (from 3d)c
84 (from 3e)c
6g
91 (from 3b)h
4dE
4eE
R
4bD; R = 4-anisyl
Synthesis 2012, 44, 2209–2216
© Georg Thieme Verlag Stuttgart · New York

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Synthesis of 2-Arylbenzothiazole Derivatives
2211
Table 1 Suzuki–Miyaura Cross-Coupling Reaction of 2-(3/4/5-Halophenyl)benzothiazole 3a–e Using 2-Phenylimidazole–PdCl2 Catalysta
(continued)
PdCl2 (0.5 mol%)
2-phenylimidazole (1.0 mol%)
Ar
X
S
S
N
Aryl
Aryl
+
Ar-B(OH)2
K2CO3 (2 equiv), DMF
120 °C, 20–30 h
N
3a–e
A–I
4aA–dI, 4eG
Ar = aryl/heteroaryl
Entry
7g
Product
Yield (%)b
Entry
16
Product
Yield (%)b
R
R
S
N
OMe
OMe
S
N
95 (from 3d)e
94 (from 3e)e
97 (from 3b)h
4dF
4eF
4bE; R = 4-tolyl
R
S
N
S
N
94 (from 3d)c
95 (from 3e)c
S
8
9
89 (from 3b)h
17
18
R
4dG
4eG
4bF; R = 3,4-dimethoxyphenyl
S
S
NO2
N
96 (from 3c)c
90 (from 3d)j
N
R
4dI
4cE; R = 4-tolyl
a Reaction conditions: Substrate 3 (1 equiv), arylboronic acid (1.5 equiv), PdCl2 (0.5 mol%), ligand (1 mol%), K2CO3 (2 equiv), DMF, 120 °C.
b Isolated yield after column chromatographic purification.
c Reaction time: 24 h.
d Reaction time: 30 h.
e Reaction time: 23 h.
f Reaction time: 20 h.
g Using arylboronic acid (3 equiv), PdCl2 (1 mol%), ligand (2 mol%), K2CO3 (4 equiv), DMF, 120 °C.
h Reaction time: 26 h.
i Reaction time: 21 h.
j Reaction time: 22 h.
needles (4.5 g, 97%); mp 93.4–93.9 °C (hexane–CHCl3, 1:2) (Lit.24
All reactions were carried out in well cleaned and oven-dried glass-
mp 91–93 °C); Rf = 0.5 (hexane–EtOAc, 9:1).
ware with magnetic stirring. Operations were performed under an
atmosphere of dry argon using Schlenk and vacuum techniques. All
starting materials were obtained from commercial sources and used
without further purification, unless otherwise stated. Activated car-
bon (Charcoal Activated) was obtained from Tokyo Chemical In-
dustry Co., Ltd (TCI). Melting points were measured by Yanaco
MP-500D and are not corrected. 1H and 13C NMR spectra (400 and
100.6 MHz, respectively) were recorded on a Jeol JNM-LA 400 in-
strument using Me4Si as an internal standard (0 ppm). Standard ab-
breviations are used to denote signal multiplicity. Mass spectra
were measured using Thermo Quest LCQ DECA plus. Elemental
analyses were carried out using Yanako CHN recorder MT-5. Pre-
parative column chromatography was carried out using Fuji Silysia
BW-820MH silica gel or YMC-GEL Silica (6 nm I-40–63 um).
TLC was carried out on Merck 25 TLC aluminum sheets coated
1H NMR (400 MHz, CDCl3): δ = 8.28–8.27 (m, 1 H, ArH), 8.08 (d,
J = 8.4 Hz, 1 H, ArH), 7.98 (d, J = 7.6 Hz, 1 H, ArH), 7.90 (d,
J = 7.6 Hz, 1 H, ArH), 7.60 (d, J = 8.8 Hz, 1 H, ArH), 7.50 (t,
J = 8.0 Hz, 1 H, ArH), 7.42–7.33 (m, 2 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 166.1, 153.9, 135.4, 135.0,
133.7, 130.5, 130.2, 126.5, 126.1, 125.5, 123.4, 123.2, 121.7.
MS (ESI): m/z = 292 (M + 2 H+), 290 (M + H+).
2-(3,5-Dibromophenyl)benzo[d]thiazole (3b)
A mixture of 2-aminothiophenol (1a; 0.5 g, 4 mmol), 3,5-dibromo-
benzaldehyde (2b; 1.06 g, 4.0 mmol), and 100 wt% of activated car-
bon (1.06 g) in xylene (10 mL) was placed in a 100 mL three-necked
flask under an O2 atmosphere and stirred at 50 °C for 28 h. The re-
action mixture was then filtered over a Celite pad. After concentra-
tion of the filtrate, the product was isolated by silica gel column
chromatography (hexane–EtOAc, 96:4) to afford 3b as colorless
needles (1.3 g, 88%); mp 153.8–154.4 °C (hexane–CHCl3, 1:2);
Rf = 0.5 (hexane–EtOAc, 9:1).
with silica gel 60 F254
.
2-(3-Bromophenyl)benzo[d]thiazole (3a)
A mixture of 2-aminothiophenol (1a; 2 g, 16 mmol), 3-bromobenz-
aldehyde (2a; 2.69 g, 16 mmol), and 100 wt% of activated carbon
(370 mg) in xylene (25 mL) was placed in a 200 mL three-necked
flask under an O2 atmosphere and stirred at 50 °C for 29 h. The re-
action mixture was then filtered over a Celite pad. After concentra-
tion of the filtrate, the product was isolated by silica gel column
chromatography (hexane–EtOAc, 96:4) to afford 3a as colorless
1H NMR (400 MHz, CDCl3): δ = 8.15 (s, 2 H, ArH), 8.07 (d, J = 8.4
Hz, 1 H, ArH), 7.91 (d, J = 7.6 Hz, 1 H, ArH), 7.77–7.75 (m, 1 H,
ArH), 7.52 (t, J = 7.6 Hz, 1 H, ArH), 7.42 (t, J = 8.4 Hz, 1 H, ArH).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2209–2216

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V. Dhayalan, M. Hayashi
PAPER
13C NMR (100.6 MHz, CDCl3): δ = 164.3, 153.8, 136.7, 136.0,
135.1, 129.0, 126.7, 125.9, 123.6, 123.5, 121.7.
MS (ESI): m/z = 372 (M + 4 H+), 370 (M + 2 H+), 368 (M + H+).
mg, 0.014 mmol), 2-(3-bromophenyl)benzo[d]thiazole (3a; 397 mg
1.37 mmol), and arylboronic acid (2.06 mmol) in anhyd DMF (12
mL). Then the mixture was stirred at 120 °C for the indicated reac-
tion time (Table 1) under argon atmosphere. The mixture was
cooled and then poured over ice-water (250 mL) containing aq 1 M
HCl (2 mL) and extracted with CHCl3 (5 × 40 mL). The combined
organic layers were washed with brine (2 × 30 mL) and dried
(Na2SO4). Removal of solvent followed by column chromatograph-
ic purification (silica gel, hexane–CHCl3) afforded the coupling
product (Table 1).
Anal. Calcd for C13H7Br2NS: C, 42.31; H, 1.91; N, 3.80. Found: C,
42.68; H, 1.41; N, 3.79.
2-(3-Iodophenyl)benzo[d]thiazole (3c)
A mixture of 2-aminothiophenol (1a; 500 mg, 4 mmol), 3-iodo-
benzaldehyde (2c; 930 mg, 4 mmol), and 100 wt% of activated car-
bon (930 mg) in xylene (10 mL) was placed in a 100 mL three-
necked flask under an O2 atmosphere and stirred at 50 °C for 24 h.
The reaction mixture was then filtered over a Celite pad. After con-
centration of the filtrate, the product was isolated by silica gel col-
umn chromatography (hexane–EtOAc, 97:3) to afford 3c as
colorless needles (1.18 g, 90%); mp 108.1–108.9 °C (hexane–
CHCl3, 1:2); Rf = 0.5 (hexane–EtOAc, 9:1).
2-(Biphenyl-3-yl)benzo[d]thiazole (4aA)
Yield: 0.372 g (94%); colorless needles; mp 116.9–117.7 °C (hex-
ane–CHCl3, 1:2); Rf = 0.6 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.33 (s, 1 H, ArH), 8.10–8.05 (m,
2 H, ArH), 7.91 (d, J = 7.6 Hz, 1 H, ArH), 7.70 (t, J = 8.0 Hz, 3 H,
ArH), 7.58–7.37 (m, 6 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 167.9, 154.2, 142.2, 140.3,
135.1, 134.1, 129.7, 129.4, 128.9, 127.8, 127.3, 126.4, 126.3, 126.2,
125.2, 123.3, 121.6.
1H NMR (400 MHz, CDCl3): δ = 8.47–8.46 (m, 1 H, ArH), 8.07 (d,
J = 8.0 Hz, 1 H, ArH), 8.00 (d, J = 8.4 Hz, 1 H, ArH), 7.90 (d,
J = 7.6 Hz, 1 H, ArH), 7.80 (d, J = 8.4 Hz, 1 H, ArH), 7.50 (t,
J = 8.4 Hz, 1 H, ArH), 7.40 (t, J = 8.0 Hz, 1 H, ArH), 7.25–7.19 (m,
1 H, ArH).
MS (ESI): m/z = 288 (M + H+).
13C NMR (100.6 MHz, CDCl3): δ = 165.9, 153.9, 139.7, 136.0,
135.4, 135.0, 130.5, 126.7, 126.5, 125.5, 123.4, 121.7, 94.7.
Anal. Calcd for C19H13NS: C, 79.41; H, 4.56; N, 4.87. Found: C,
79.01; H, 4.50; N, 4.90.
MS (ESI): m/z = 338 (M + H+).
2-[3-(Naphthalen-1-yl)phenyl]benzo[d]thiazole (4aB)
Yield: 0.455 g (98%); colorless needles; mp 135.9–136.3 °C (hex-
ane–CHCl3, 1:2); Rf = 0.6 (hexane–EtOAc, 4:1).
Anal. Calcd for C13H8INS: C, 46.31; H, 2.39; N, 4.15. Found: C,
46.52; H, 2.41; N, 4.26.
1H NMR (400 MHz, CDCl3): δ = 8.22 (s, 1 H, ArH), 8.19–8.15 (m,
1 H, ArH), 8.06 (d, J = 8.4 Hz, 1 H, ArH), 7.93–7.87 (m, 4 H, ArH),
7.61–7.42 (m, 7 H, ArH), 7.37 (t, J = 8.0 Hz, 1 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 167.8, 154.1, 141.7, 139.2,
135.1, 133.8, 132.6, 131.5, 129.1, 128.9, 128.3, 128.1, 127.1, 126.4,
126.3 (2 C), 125.9, 125.7, 125.3, 125.2, 123.3, 121.6.
2-(4-Bromophenyl)benzo[d]thiazole (3d)
A mixture of 2-aminothiophenol (1a; 250 mg, 1.99 mmol), 4-bro-
mobenzaldehyde (2d; 370 mg, 1.99 mmol), and 100 wt% of activat-
ed carbon (370 mg) in xylene (5 mL) was placed in a 100 mL three-
necked flask under an O2 atmosphere and stirred at 50 °C for 24 h.
The reaction mixture was then filtered over a Celite pad. After con-
centration of the filtrate, the product was isolated by silica gel col-
umn chromatography (hexane–EtOAc, 96:4) to afford 3d as
colorless needles (0.49 g, 84%); mp 134.3–134.9 °C (hexane–
CHCl3, 1:2) (Lit.25 mp 133–134 °C); Rf = 0.5 (hexane–EtOAc, 9:1).
MS (ESI): m/z = 338 (M + H+).
Anal. Calcd for C23H15NS: C, 81.87; H, 4.48; N, 4.15. Found: C,
81.41; H, 4.41; N, 4.24.
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.0 Hz, 1 H, ArH),
7.97–7.89 (m, 3 H, ArH), 7.64–7.61 (m, 2 H, ArH), 7.50 (t, J = 8.0
Hz, 1 H, ArH), 7.40 (t, J = 8.4 Hz, 1 H, ArH).
2-(2′,4′,6′-Trimethylbiphenyl-3-yl)benzo[d]thiazole (4aC)
Yield: 0.345 g (76%); colorless needles; mp 101.5–102.9 °C (hex-
ane–CHCl3, 1:2); Rf = 0.7 (hexane–EtOAc, 4:1).
13C NMR (100.6 MHz, CDCl3): δ = 166.6, 154.0, 135.0, 132.5,
132.2, 128.9, 126.5, 125.4 (2 C), 123.3, 121.6.
MS (ESI): m/z = 292 (M + 2 H+), 290 (M + H+).
1H NMR (400 MHz, CDCl3): δ = 8.07 (t, J = 8.8 Hz, 2 H, ArH),
7.89 (d, J = 7.2 Hz, 2 H, ArH), 7.55 (t, J = 8.0 Hz, 1 H, ArH), 7.48
(t, J = 7.6 Hz, 1 H, ArH), 7.39 (t, J = 7.6 Hz, 1 H, ArH), 7.27 (t,
J = 7.6 Hz, 1 H, ArH), 6.97 (s, 2 H, ArH), 2.35 (s, 3 H, CH3), 2.05
(s, 6 H, CH3).
2-(4-Iodophenyl)benzo[d]thiazole (3e)
A mixture of 2-aminothiophenol (1a; 250 mg, 2.4 mmol), 4-iodo-
benzaldehyde (2e; 550 mg, 2.4 mmol), and 100 wt% of activated
carbon (550 mg) in xylene (6 mL) was placed in a 100 mL three-
necked flask under an O2 atmosphere and stirred at 50 °C for 24 h.
The reaction mixture was then filtered using Celite. After concen-
tration of the filtrate, the product was isolated by silica gel column
chromatography (hexane–EtOAc, 97:3) to afford 3e as colorless
needles (0.72 g, 90%); mp 156.6–157.2 °C (hexane–CHCl3, 1:2)
(Lit.26 mp 134–135 °C); Rf = 0.5 (hexane–EtOAc, 9:1).
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.0 Hz, 1 H, ArH),
7.90–7.79 (m, 5 H, ArH), 7.49 (t, J = 8.4 Hz, 1 H, ArH), 7.39 (t,
J = 8.4 Hz, 1 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 166.8, 154.0, 138.1, 134.9,
133.0, 128.9, 126.5, 125.4, 123.3, 121.6, 97.5.
13C NMR (100.6 MHz, CDCl3): δ = 168.1, 154.2, 142.1, 138.0,
137.0, 135.9, 135.1, 133.9, 132.1, 129.2, 128.5, 128.2, 126.3, 125.8,
125.2, 123.2, 121.6, 21.0, 20.8.
MS (ESI): m/z = 330 (M + H+).
Anal. Calcd for C22H19NS: C, 80.20; H, 5.81; N, 4.25. Found: C,
79.91; H, 5.58; N, 4.25.
2-(4′-Methoxybiphenyl-3-yl)benzo[d]thiazole (4aD)
Yield: 0.401 g (92%); pale yellow needles; mp 105.8–106.3 °C
(hexane–CHCl3, 1:2); Rf = 0.5 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 H, ArH), 8.09 (d, J = 8.4
Hz, 1 H, ArH), 7.99 (d, J = 8.0 Hz, 1 H, ArH), 7.89 (d, J = 7.6 Hz,
1 H, ArH), 7.66–7.59 (m, 3 H, ArH), 7.53–7.47 (m, 2 H, ArH), 7.38
(t, J = 8.0 Hz, 1 H, ArH), 7.00 (d, J = 8.8 Hz, 2 H, ArH), 3.85 (s, 3
H, OCH3).
MS (ESI): m/z = 338 (M + H+).
13C NMR (100.6 MHz, CDCl3): δ = 168.0, 159.5, 154.1, 141.7,
135.1, 134.0, 132.7, 129.4, 129.2, 128.3, 126.3, 125.8, 125.7, 125.2,
123.2, 121.6, 114.3, 55.3.
Suzuki–Miyaura Cross-Coupling Reaction of 3-Bromophenyl-
benzothiazole 3a with Arylboronic Acids; General Procedure
K2CO3 (380 mg, 2.75 mmol) was added to a Schlenk tube equipped
with a stirring bar and the tube was dried under vacuum and filled
with argon, PdCl2 (1.24 mg, 0.007 mmol), 2-phenylimidazole (2
MS (ESI): m/z = 318 (M + H+).
Synthesis 2012, 44, 2209–2216
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 2-Arylbenzothiazole Derivatives
2213
Anal. Calcd for C20H15NOS: C, 75.68; H, 4.76; N, 4.41. Found: C,
75.74; H, 4.79; N, 4.58.
2-[3,5-Di(3,4-dimethoxyphenyl)]benzo[d]thiazole (4bF)
Yield: 0.350 g (89%); colorless prisms; mp 189.8–190.2 °C
(EtOAc–CHCl3, 1:1); Rf = 0.5 (hexane–EtOAc, 1:1).
Suzuki–Miyaura Cross-Coupling Reaction of 3,5-Dibromo-
phenylbenzothiazole 3b with Arylboronic Acids; General Pro-
cedure
1H NMR (400 MHz, CDCl3): δ = 8.20 (s, 1 H, ArH), 8.19 (s, 1 H,
ArH), 8.12 (d, J = 8.0 Hz, 1 H, ArH), 7.93 (d, J = 7.6 Hz, 1 H, ArH),
7.82 (s, 1 H, ArH), 7.52 (t, J = 7.2 Hz, 1 H, ArH), 7.40 (t, J = 7.6
Hz, 1 H, ArH), 7.27 (d, J = 8.4 Hz, 2 H, ArH), 7.22 (s, 2 H, ArH),
7.00 (d, J = 8.4 Hz, 2 H, ArH), 4.00 (s, 6 H, OCH3), 3.95 (s, 6 H,
OCH3).
13C NMR (100.6 MHz, CDCl3): δ = 167.9, 154.1, 149.2, 149.0,
142.5, 135.0, 134.4, 133.2, 128.1, 126.3, 125.3, 124.4, 123.2, 121.6,
119.7, 111.4, 110.5, 56.1, 55.9.
K2CO3 (450 mg, 3.25 mmol) was added to a Schlenk tube equipped
with a stirring bar and the tube was dried under vacuum and filled
with argon, PdCl2 (1.4 mg, 0.008 mmol), 2-phenylimidazole (2.3
mg, 0.016 mmol), 2-(3,5-dibromophenyl)benzo[d]thiazole (3b; 300
mg, 0.81 mmol), and arylboronic acid (2.43 mmol) in anhyd DMF
(17 mL). Then the mixture was stirred at 120 °C for the indicated
reaction time (Table 1) under argon atmosphere. The mixture was
cooled and then poured over ice-water (250 mL) containing aq 1 M
HCl (2 mL) and extracted with CHCl3 (5 × 40 mL). The combined
organic layers were washed with brine (2 × 30 mL) and dried
(Na2SO4). Removal of solvent followed by column chromatograph-
ic purification (silica gel, hexane–CHCl3) afforded the coupling
product (Table 1).
MS (ESI): m/z = 484 (M + H+).
Anal. Calcd for C29H25NO4S: C, 72.03; H, 5.21; N, 2.90. Found: C,
71.75; H, 5.18; N, 2.98.
Suzuki–Miyaura Cross-Coupling Reaction of 3-Iodophenylben-
zothiazole 3c with Arylboronic Acids; General Procedure
K2CO3 (246 mg, 1.78 mmol) was added to a Schlenk tube equipped
with a stirring bar and the tube was dried under vacuum and filled
with argon, PdCl2 (0.7 mg, 0.004 mmol), 2-phenylimidazole (1.3
mg, 0.009 mmol), 2-(3-iodophenyl)benzo[d]thiazole (3c; 300 mg,
0.89 mmol), and arylboronic acid (1.33 mmol) in anhyd DMF (10
mL). Then, the mixture was stirred at 120 °C for the indicated reac-
tion time (Table 1) under argon atmosphere. The mixture was
cooled and then poured over ice-water (300 mL) containing aq 1 M
HCl (2 mL) and extracted with CHCl3 (5 × 50 mL). The combined
organic layers were washed with brine (2 × 30 mL) and dried
(Na2SO4). Removal of solvent followed by column chromatograph-
ic purification (silica gel, hexane–CHCl3) afforded the coupling
product (Table 1).
2-[(3,5-Diphenyl)phenyl]benzo[d]thiazole (4bA)
Yield: 0.261 (88%); colorless needles; mp 161.8–162.2 °C (hex-
ane–CHCl3, 1:2); Rf = 0.6 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 H, ArH), 8.27 (s, 1 H,
ArH), 8.10 (d, J = 8.0 Hz, 1 H, ArH), 7.91–7.89 (m, 2 H, ArH), 7.72
(d, J = 7.2 Hz, 4 H, ArH), 7.49 (t, J = 8.4 Hz, 5 H, ArH), 7.43–7.36
(m, 3 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 167.8, 154.1, 142.7, 140.2,
135.1, 134.6, 128.9, 128.6, 127.9, 127.3, 126.3, 125.3, 125.1, 123.3,
121.6.
MS (ESI): m/z = 364 (M + H+).
Anal. Calcd for C25H17NS: C, 41.61; H, 4.71; N, 3.85. Found: C,
41.58; H, 4.68; N, 3.93.
2-(4′-Methylbiphenyl-3-yl)benzo[d]thiazole (4cE)
Yield: 0.25 g (96%); colorless prisms; mp 84.1–84.8 °C (hexane–
EtOAc, 1:2); Rf = 0.6 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.30 (s, 1 H, ArH), 8.09 (d, J = 8.4
Hz, 1 H, ArH), 8.02 (d, J = 7.6 Hz, 1 H, ArH), 7.89 (d, J = 7.6 Hz,
1 H, ArH), 7.68 (d, J = 7.6 Hz, 1 H, ArH), 7.58–7.46 (m, 4 H, ArH),
7.37 (t, J = 7.2 Hz, 1 H, ArH), 7.27 (d, J = 8.0 Hz, 2 H, ArH), 2.40
(s, 3 H, CH3).
2-[(3,5-Dianisyl)phenyl]benzo[d]thiazole (4bD)
Yield: 0.312 g (91%); colorless needles; mp 160.2–160.8 °C (hex-
ane–EtOAc, 1:3); Rf = 0.4 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.19 (s, 1 H, ArH), 8.18 (s, 1 H,
ArH), 8.10 (d, J = 8.4 Hz, 1 H, ArH), 7.90 (d, J = 7.6 Hz, 1 H, ArH),
7.81 (s, 1 H, ArH), 7.65 (d, J = 8.8 Hz, 4 H, ArH), 7.50 (t, J = 8.0
Hz, 1 H, ArH), 7.38 (t, J = 8.0 Hz, 1 H, ArH), 7.01 (d, J = 8.8 Hz, 4
H, ArH), 3.86 (s, 6 H, OCH3).
13C NMR (100.6 MHz, CDCl3): δ = 168.1, 159.5, 154.1, 142.2,
135.1, 134.5, 132.8, 128.4, 127.7, 126.3, 125.2, 124.1, 123.2, 121.6,
114.3, 55.3.
13C NMR (100.6 MHz, CDCl3): δ = 168.0, 154.2, 142.0, 137.6,
137.3, 135.1, 134.1, 129.6, 129.5, 129.4, 127.1, 126.3, 126.1, 126.0,
125.2, 123.2, 121.6, 21.1.
MS (ESI): m/z = 302 (M + H+).
MS (ESI): m/z = 424 (M + H+).
Anal. Calcd for C20H15NS: C, 79.70; H, 5.02; N, 4.65. Found: C,
79.54; H, 4.95; N, 4.63.
Anal. Calcd for C27H21NO2S: C, 76.57; H, 5.00; N, 3.31. Found: C,
76.37; H, 5.00; N, 3.47.
2-(3′,4′-Dimethoxybiphenyl-3-yl)benzo[d]thiazole (4cF)
Yield: 0.295 g (96%); colorless powder; mp 127.5–128.1 °C (hex-
ane–EtOAc, 1:2); Rf = 0.3 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.28 (s, 1 H, ArH), 8.10 (d, J = 8.4
Hz, 1 H, ArH), 8.01 (d, J = 7.6 Hz, 1 H, ArH), 7.91 (d, J = 8.0 Hz,
1 H, ArH), 7.67 (d, J = 8.0 Hz, 1 H, ArH), 7.55–7.48 (m, 2 H, ArH),
7.39 (t, J = 7.6 Hz, 1 H, ArH), 7.25–7.18 (m, 2 H, ArH), 6.97 (d,
J = 8.4 Hz, 1 H, ArH), 3.98 (s, 3 H, OCH3), 3.94 (s, 3 H, OCH3).
2-[(3,5-Ditolyl)phenyl]benzo[d]thiazole (4bE)
Yield: 0.308 g (97%); colorless needles; mp 184.4–184.8 °C
(EtOAc–CHCl3, 1:1); Rf = 0.6 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.23 (d, J = 8.4 Hz, 2 H, ArH),
8.10 (t, J = 8.0 Hz, 1 H, ArH), 7.92–7.86 (m, 2 H, ArH), 7.61 (t,
J = 8.4 Hz, 4 H, ArH), 7.52–7.45 (m, 1 H, ArH), 7.40–7.34 (m, 1 H,
ArH), 7.29 (t, J = 8.4 Hz, 4 H, ArH), 2.42 (s, 3 H, CH3), 2.40 (s, 3
H, CH3).
13C NMR (100.6 MHz, CDCl3): δ = 168.0, 154.2, 142.5, 137.7,
137.4, 135.1, 134.5, 129.6, 128.2, 127.1, 126.3, 125.2, 124.7, 123.3,
121.6, 21.1.
13C NMR (100.6 MHz, CDCl3): δ = 168.0, 154.1, 149.2, 149.0,
142.0, 135.0, 134.0, 133.2, 129.4, 129.3, 126.3, 126.0, 125.8, 125.2,
123.2, 121.6, 119.6, 111.4, 110.4, 56.0, 55.9.
MS (ESI): m/z = 348 (M + H+).
MS (ESI): m/z = 392 (M + H+).
Anal. Calcd for C21H17NO2S: C, 72.60; H, 4.93; N, 4.03. Found: C,
72.29; H, 4.80; N, 4.00.
Anal. Calcd for C27H21NS: C, 41.83; H, 5.41; N, 3.58. Found: C,
41.61; H, 5.37; N, 3.67.
2-[3-(Thiophen-2-yl)phenyl]benzo[d]thiazole (4cG)
Yield: 0.256 g (98%); pale yellow prisms; mp 109.7–110.1 °C (hex-
ane–EtOAc, 1:2); Rf = 0.5 (hexane–EtOAc, 4:1).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 2209–2216

2214
V. Dhayalan, M. Hayashi
PAPER
1H NMR (400 MHz, CDCl3): δ = 8.33 (s, 1 H, ArH), 8.09 (d, J = 8.4
Hz, 1 H, ArH), 7.96 (d, J = 7.6 Hz, 1 H, ArH), 7.90 (d, J = 8.0 Hz,
1 H, ArH), 7.70 (d, J = 7.6 Hz, 1 H, ArH), 7.51–7.31 (m, 5 H, ArH),
7.10 (t, J = 5.6 Hz, 1 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 167.6, 154.1, 143.3, 135.3,
135.1, 134.2, 129.5, 128.3, 128.1, 126.5, 126.4, 125.4, 125.3, 124.7,
123.9, 123.3, 121.6.
Anal. Calcd for C20H15NOS: C, 75.68; H, 4.76; N, 4.41. Found: C,
75.38; H, 4.71; N, 4.54.
2-(4′-Methylbiphenyl-4-yl)benzo[d]thiazole (4dE)
Yield: 0.207 g (86%); pale yellow dendrites; mp 215.3–216.1 °C
(hexane–CHCl3, 1:2); Rf = 0.6 (hexane–EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 7.6 Hz, 2 H, ArH),
8.08 (d, J = 8.4 Hz, 1 H, ArH), 7.89 (d, J = 7.6 Hz, 1 H, ArH), 7.69
(d, J = 8.4 Hz, 2 H, ArH), 7.54 (d, J = 7.6 Hz, 2 H, ArH), 7.49 (t,
J = 7.2 Hz, 1 H, ArH), 7.37 (t, J = 7.2 Hz, 1 H, ArH), 7.27 (d,
J = 8.4 Hz, 2 H, ArH), 2.40 (s, 3 H, CH3).
MS (ESI): m/z = 294 (M + H+).
Anal. Calcd for C17H11NS2: C, 69.59; H, 3.78; N, 4.77. Found: C,
69.65; H, 3.77; N, 4.84.
13C NMR (100.6 MHz, CDCl3): δ = 167.7, 154.2, 143.6, 137.8,
137.1, 135.0, 132.1, 129.6, 127.9, 127.3, 126.9, 126.3, 125.1, 123.1,
121.6, 21.1.
2-[3-(1H-Indol-5-yl)phenyl]benzo[d]thiazole (4cH)
Yield: 0.283 g (98%); colorless needles; mp 159.1–160.2 °C (hex-
ane–EtOAc, 1:2); Rf = 0.7 (hexane–EtOAc, 1:1).
1H NMR (400 MHz, CDCl3): δ = 8.38 (s, 1 H, ArH), 8.35 (s, 1 H,
NH), 8.10 (d, J = 8.0 Hz, 1 H, ArH), 8.03 (d, J = 7.2 Hz, 1 H, ArH),
7.95 (s, 1 H, ArH), 7.91 (d, J = 8.0 Hz, 1 H, ArH), 7.77 (d, J = 7.2
Hz, 1 H, ArH), 7.57–7.45 (m, 4 H, ArH), 7.39 (t, J = 7.6 Hz, 1 H,
ArH), 7.25–7.23 (m, 1 H, ArH), 6.63–6.62 (m, 1 H, ArH).
MS (ESI): m/z = 302 (M + H+).
Anal. Calcd for C20H15NS: C, 79.70; H, 5.02; N, 4.65. Found: C,
79.54; H, 4.94; N, 4.97.
2-(3′,4′-Dimethoxylbiphenyl-4-yl)benzo[d]thiazole (4dF)
Yield: 0.228 g (95%); colorless needles; mp 193.6–194.3 °C
(EtOAc–CHCl3, 1:1); Rf = 0.6 (hexane–EtOAc, 1:1).
1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 8.4 Hz, 2 H, ArH),
8.07 (d, J = 8.0 Hz, 1 H, ArH), 7.88 (d, J = 8.0 Hz, 1 H, ArH), 7.66
(d, J = 8.0 Hz, 2 H, ArH), 7.47 (t, J = 8.4 Hz, 1 H, ArH), 7.36 (t,
J = 8.4 Hz, 1 H, ArH), 7.24–7.16 (m, 2 H, ArH), 6.95 (d, J = 8.4 Hz,
1 H, ArH), 3.95 (s, 3 H, OCH3), 3.92 (s, 3 H, OCH3).
13C NMR (100.6 MHz, CDCl3): δ = 168.4, 154.2, 143.5, 135.5,
135.1, 133.9, 132.3, 130.0, 129.3, 128.4, 126.4, 126.3, 125.5, 125.1,
125.0, 123.2, 121.8, 121.6, 119.4, 111.4, 103.1.
MS (ESI): m/z = 327 (M + H+).
Anal. Calcd for C21H14N2S: C, 77.27; H, 4.32; N, 8.58. Found: C,
77.02; H, 4.31; N, 8.50.
13C NMR (100.6 MHz, CDCl3): δ = 167.7, 154.2, 149.3, 149.2,
143.5, 135.0, 132.9, 132.0, 127.9, 127.2, 126.3, 125.1, 123.1, 121.6,
119.5, 111.5, 110.2, 56.0.
Suzuki–Miyaura Cross-Coupling Reaction of 4-Bromophenyl-
benzothiazole 3d with Arylboronic Acids; General Procedure
K2CO3 (380 mg, 2.75 mmol) was added to a Schlenk tube equipped
with a stirring bar and the tube was dried under vacuum and filled
with argon, PdCl2 (1.24 mg, 0.007 mmol), 2-phenylimidazole (2
mg, 0.014 mmol), 2-(4-bromophenyl)benzo[d]thiazole (3d; 397
mg, 1.37 mmol), and arylboronic acid (2.06 mmol) in anhyd DMF
(12 mL). Then the mixture was stirred at 120 °C for the indicated
reaction time (Table 1) under argon atmosphere. The mixture was
cooled and then poured over ice-water (250 mL) containing aq 1 M
HCl (2 mL) and extracted with CHCl3 (5 × 40 mL). The combined
organic layers were washed with brine (2 × 30 mL) and dried
(Na2SO4). Removal of solvent followed by column chromatograph-
ic purification (silica gel, hexane–CHCl3) afforded the coupling
product (Table 1).
MS (ESI): m/z = 348 (M + H+).
Anal. Calcd for C21H17NO2S: C, 72.60; H, 4.93; N, 4.03. Found: C,
72.35; H, 4.95; N, 4.11.
2-[4-(Thiophen-2-yl)phenyl]benzo[d]thiazole (4dG)
Yield: 0.190 g (94%); pale yellow prisms; mp 210.6–211.5 °C
(EtOAc–CHCl3, 1:1) (Lit.27 mp 205.5–206.1 °C); Rf = 0.5 (hexane–
EtOAc, 4:1).
1H NMR (400 MHz, CDCl3): δ = 8.09–8.06 (m, 3 H, ArH), 7.89 (d,
J = 7.6 Hz, 1 H, ArH), 7.71 (d, J = 8.0 Hz, 2 H, ArH), 7.49 (t,
J = 7.6 Hz, 1 H, ArH), 7.41–7.33 (m, 3 H, ArH), 7.11 (t, J = 5.6 Hz,
1 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 167.4, 154.1, 143.2, 136.8,
135.0, 132.4, 128.3, 128.0, 126.3, 126.1, 125.8, 125.2, 124.0, 123.1,
121.6.
2-(Biphenyl-4-yl)benzo[d]thiazole (4dA)
Yield: 0.316 g (80%); colorless powder; mp 208.1–209.0 °C
(EtOAc–CHCl3, 1:1) (Lit.20 mp 192–194 °C); Rf = 0.4 (hexane–
EtOAc, 9:1).
1H NMR (400 MHz, CDCl3): δ = 8.15 (d, J = 7.6 Hz, 2 H, ArH),
8.08 (d, J = 8.4 Hz, 1 H, ArH), 7.89 (d, J = 8.0 Hz, 1 H, ArH), 7.71
(d, J = 8.4 Hz, 2 H, ArH), 7.64 (d, J = 7.6 Hz, 2 H, ArH), 7.51–7.45
(m, 3 H, ArH), 7.38 (t, J = 8.8 Hz, 2 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 167.7, 154.2, 143.7, 140.0,
135.0, 132.5, 128.9, 128.0, 127.9, 127.6, 127.1, 126.3, 125.2, 123.2,
121.6.
2-(4′-Nitrobiphenyl-4-yl)benzo[d]thiazole (4dI)
Yield: 0.41 g (90%); yellow powder; mp 267.5–269.6 °C (CHCl3);
Rf = 0.2 (hexane–EtOAc, 9:1).
1H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 8.8 Hz, 2 H, ArH),
8.21 (d, J = 8.0 Hz, 2 H, ArH), 8.09 (d, J = 7.6 Hz, 1 H, ArH), 7.92
(d, J = 8.8 Hz, 1 H, ArH), 7.80–7.73 (m, 4 H, ArH), 7.50 (t, J = 7.2
Hz, 1 H, ArH), 7.40 (t, J = 8.0 Hz, 1 H, ArH).
13C NMR (100.6 MHz, CDCl3): δ = 166.9, 154.5, 147.6, 146.5,
141.2, 135.2, 134.4, 128.4, 128.0, 127.9, 126.6, 125.6, 124.3, 123.6,
121.7.
2-(4′-Methoxylbiphenyl-4-yl)benzo[d]thiazole (4dD)
Yield: 0.421 g (96%); colorless powder; mp 232.9–233.4 °C
(CHCl3); Rf = 0.3 (hexane–EtOAc, 9:1).
1H NMR (400 MHz, CDCl3): δ = 8.13 (d, J = 8.4 Hz, 2 H, ArH),
8.07 (d, J = 8.4 Hz, 1 H, ArH), 7.89 (d, J = 8.4 Hz, 1 H, ArH), 7.66
(d, J = 8.4 Hz, 2 H, ArH), 7.58 (d, J = 8.8 Hz, 2 H, ArH), 7.47 (t,
J = 7.6 Hz, 1 H, ArH), 7.36 (t, J = 8.4 Hz, 1 H, ArH), 6.99 (d,
J = 8.8 Hz, 2 H, ArH), 3.85 (s, 3 H, OCH3).
MS (ESI): m/z = 333 (M + H+).
Anal. Calcd for C19H12N2O2S: C, 68.66; H, 3.64; N, 8.43. Found: C,
68.85; H, 3.62; N, 8.50.
Suzuki–Miyaura Cross-Coupling Reaction of 4-Iodophenylben-
zothiazole 3e with Arylboronic Acids; General procedure
K2CO3 (246 mg, 1.78 mmol) was added to a Schlenk tube equipped
with a stirring bar and the tube was dried under vacuum and filled
with argon, PdCl2 (0.7 mg, 0.004 mmol), 2-phenylimidazole (1.3
mg, 0.009 mmol), 2-(4-iodophenyl)benzo[d]thiazole (3e; 300 mg,
13C NMR (100.6 MHz, CDCl3): δ = 167.8, 160.0, 154.5, 143.5,
135.3, 132.8, 132.2, 128.2, 128.1, 127.1, 126.3, 125.1, 123.3, 121.6,
114.6, 55.4.
MS (ESI): m/z = 318 (M + H+).
Synthesis 2012, 44, 2209–2216
© Georg Thieme Verlag Stuttgart · New York

PAPER
Synthesis of 2-Arylbenzothiazole Derivatives
2215
0.89 mmol), and arylboronic acid (1.33 mmol) in anhyd DMF (10
mL). Then, the mixture was stirred at 120 °C for the indicated reac-
tion time (Table 1) under argon atmosphere. The mixture was
cooled and then poured over ice-water (200 mL) containing aq 1 M
HCl (2 mL) and extracted with CHCl3 (5 × 50 mL). The combined
organic layers were washed with brine (2 × 30 mL) and dried
(Na2SO4). Removal of solvent followed by column chromatograph-
ic purification (silica gel, hexane–CHCl3) afforded the coupling
product (Table 1).
Bioorg. Med. Chem. 2008, 16, 3626. (b) Wang, M.; Gao, M.;
Mock, B.; Miller, K.; Sledge, G.; Hutchins, G.; Zheng, Q.
Bioorg. Med. Chem. 2006, 14, 8599. (c) Hutchinson, I.;
Chua, M. S.; Browne, H. L.; Trapani, V.; Bradshaw, T. D.;
Westwell, A. D. J. Med. Chem. 2001, 44, 1446.
(6) (a) Sadek, B.; Tabakha, M. M. A.; Fahelelbom, K. M. S.
Molecules 2011, 16, 9386. (b) Pal, N.; Kumar, M.; Seth, G.
E-J. Chem. 2011, 8, 1174.
(7) (a) Arora, P.; Das, S.; Ranawat, M. S.; Arora, N.; Gupta, M.
M. J. Chem. Pharm. Res. 2010, 2, 317. (b) Gawai, A.; Das,
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(8) Yar, M. H.; Ansari, Z. H. Acta Pol. Pharm. 2009, 66, 387;
Chem. Abstr. 2010, 153, 530327.
2-(Biphenyl-4-yl)benzo[d]thiazole (4eA)
Yield: 0.241 g (95%); colorless powder; mp 209.8–210.6 °C
(EtOAc–CHCl3, 1:1).
The spectral data are similar to that of compound 4dA.
(9) Maharan, M.; William, S.; Ramzy, F.; Sembel, A. Molecules
2007, 12, 622.
2-(4′-Methylbiphenyl-4-yl)benzo[d]thiazole (4eE)
Yield: 0.225 g (84%); pale yellow dendrites; mp 212.4–213.7 °C
(hexane–CHCl3, 1:2).
(10) Sreenivasa, M.; Jaychand, E.; Shivakumar, B.; Jayrajkumar,
K.; Vijaykumar, J. Arch. Pharm. Sci. Res. 2009, 1, 150.
(11) (a) Pattan, S.; Suresh, C.; Pujar, V.; Reddy, V.; Rasal, V.;
Koti, B. Ind. J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.
2005, 44, 2404. (b) Vazquez, G. N.; Paoli, P.; Rivera, I. L.;
Molina, R. V.; Franco, J.; Andrade, R. O.; Soto, S. E.;
Camici, G.; Coutino, D.; Ortiz, I.; Mayorga, K.; Diaz, H.
Bioorg. Med. Chem. 2009, 17, 3332. (c) Surya, K. D.; Chen,
L. H.; Stebbins, J. L.; Machleidt, T.; Mehan, M.; Dahl, R.;
Yuan, H. C.; Barile, E.; Emdadi, A.; Murphy, R.; Pellecchia,
M. Bioorg. Med. Chem. 2009, 17, 2712.
(12) For other bioactivity, see: (a) Mathis, C. A.; Wang, Y.; Holt,
D. P.; Huang, G.-F.; Debnath, M. L.; Klunk, W. E. J. Med.
Chem. 2003, 46, 2740. (b) Henriksen, G.; Hauser, A. I.;
Westwell, A. D.; Yousefi, B. H.; Schwaiger, M.; Drzezga,
A.; Wester, H. J. J. Med. Chem. 2007, 50, 1087. (c) Cui, M.
C.; Li, Z. J.; Tang, R. K.; Liu, B. L. Bioorg. Med. Chem.
2010, 14, 1777. (d) Yadav, P. S.; Devprakash;
The spectral data are similar to that of compound 4dE.
2-(3′,4′-Dimethoxylbiphenyl-4-yl)benzo[d]thiazole (4eF)
Yield: 0.288 g (94%); colorless needles; mp 191.6–192.6 °C
(EtOAc–CHCl3, 1:1).
The spectral data are similar to that of compound 4dF.
2-[4-(Thiophen-2-yl)phenyl]benzo[d]thiazole (4eG)
Yield: 0.247 g (95%); pale yellow prisms; mp 208.5–209.8 °C
(EtOAc–CHCl3, 1:1).
The spectral data are similar to that of compound 4dG.
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
on Innovative Areas, MEXT, Japan ‘Molecular Activation Directed
toward Straightforward Synthesis’, No. B23350043 from the Mini-
stry of Education, Culture, Sports, Science and Technology, Japan.
Special Coordination Funds for Promoting Science and Technolo-
gy, Creation of Innovation Centers for Advanced Interdisciplinary
Research Areas (Innovative Bioproduction Kobe), MEXT, Japan is
also acknowledged.
Senthilkumar, G. P. IJPSR 2011, 3, 1. (e) Khokra, S. L.;
Arora, K.; Mehta, H.; Aggarwal, A.; Yadav, M. IJPSR 2011,
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