Supporting Information
Synthesis of Benzothiazoles through Copper-Catalyzed
One-Pot Three-Component Reactions in water
Hualong Xu,[a] Chun Luo,[a] Zhengkai Li,[a] Haifeng Xiang,[a] Xiangge Zhou*[a] [b]
[a] Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University,
Chengdu 610064, China
[b] Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry,
Chemical Engineering and Materials Science, Soochow University, Suzhou 215123
(China)
E-mail: zhouxiangge@scu.edu.cn
Table of Contents
1. General methods ………………………………………………………………..1
2. General procedure for the synthesis of substituted benzothiazoles……………… 2
3. Characterization data……………………………………………………………….…. .2-6
4. NMR spectra of compounds……………………………………………………….......7-23
1.General Methods:
Analytical thin layer chromatography (TLC) was performed using Merck silica gel
GF254 plates. Column chromatography was performed using silica gel (200-300 mesh)
eluting with ethyl acetate and petroleum ether. All products were characterized by
their NMR. 1H NMR spectra were recorded at 400 MHz and 13C NMR spectra were
recorded at 100 MHz (Bruker DPX) with CDCl3 or DMSO-d6 as solvent. Chemical
shifts are reported in ppm using TMS as internal standard.
1
2.General procedure for the synthesis of substituted benzothiazoles
General procedure: 2-Iodoaniline (0.3 mmol), benzylamine (0.6 mmol), sulfur powder
(0.9 mmol), CuCl2·2H2O (0.03 mmol), 1,10-Phen(0.03 mmol) in water (4 mL) were
put into a Teflon septum screw-capped tube. The reaction mixture was stirred at
140 ℃ for 24 h without an inert gas atmosphere and then cooled to room temperature
and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and the
solvent was removed under reduced pressure. The residue was purified by silica-gel
column chromatography to afford the corresponding product.
3. Characterization data
2-(4-Methoxyphenyl)benzothiazole[1] (a)
N
OCH3
S
Purified by flash chromatography (petroleum ether/ethyl acetate 10:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.05-8.08 (m, 3H), 7.90-7.92 (d, J = 8.0 Hz, 1H), 7.50 (t,
J= 7.6 Hz, 1H), 7.38 (t, J =7.6 Hz, 1H), 7.02-7.04 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H);
13
C NMR (100 MHz, CDCl3): 167.90, 161.96, 154.12, 134.80, 129.15, 126.37, 126.24,
124.83, 122.80, 121.52, 114.39, 55.48; MS (EI, m/z): 241 [M+].
2-(3-Methoxyphenyl)benzothiazole[1] (b)
OCH3
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 10:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.10-8.12 (d, J = 8.2 Hz, 1H), 7.92-7.94 (d, J = 8.0 Hz,
1H), 7.66-7.71 (m, 2H), 7.52 (t, J = 8.0 Hz, 1H), 7.40-7.44 (m, 2H), 7.06-7.08 (dd, J =
2.4, 8.2 Hz, 1H), 3.95 (s, 3H); 13C NMR (100 MHz, CDCl3): 167.95, 160.06, 154.06,
135.09, 134.90, 130.05, 126.33, 125.24, 123.25, 121.62, 120.25, 117.36, 112.03,
55.53. MS (EI, m/z): 241 [M+].
2-(2-Methoxyphenyl)benzothiazole[2] (c)
H3CO
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 10:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.56-8.59 (d, J = 7.7 Hz, 1H), 8.12-8.15 (d, J = 8.0 Hz,
1H), 7.95-7.97(d, J = 8.0 Hz, 1H), 7.40-7.53(m, 3 H), 7.08-7.19(m, 2H), 4.08(s, 3H);
13
C NMR (100 MHz, CDCl3): 163.15, 157.24, 152.16, 136.13, 131.79, 129.56, 125.91,
124.60, 122.80, 122,29, 121.22, 121.18, 111.69, 55.72. MS (EI, m/z): 241 [M+].
2
2-(3,4-dimethoxyphenyl)benzothiazole[1] (d)
OCH 3
N
OCH 3
S
Purified by flash chromatography (petroleum ether/ethyl acetate 10:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.04-8.06(d, J = 8.0 Hz, 1H), 7.87-7.89(d, J = 8.0 Hz,
1H), 7.73(s, 1H), 7.59-7.62(dd, J = 8.4, 2.0 Hz, 1H), 7.47-7.49(t, J = 7.6 Hz, 1H),
7.37-7.39(m, 1H), 6.93-6.96(d, J = 8.4 Hz, 1H), 4.04(s, 3H), 3.96(s, 3H); 13C NMR
(100 MHz, CDCl3): 167.93, 154.12, 151.55, 151.43, 149.32, 134.88, 126.64, 126.23,
124.88, 122.82, 121.51, 121.15, 110.99, 109.74, 56.13, 56.04. MS (EI, m/z): 271
[M+].
2-(4-Fluorophenyl)benzothiazole[1] (e)
N
F
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.08-8.13 (m, 3H), 7.92 (d, J = 8.1 Hz, 1H), 7.52 (t, J =
7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 8.4 Hz, 2H); 13C NMR (100 MHz,
CDCl3): 166.77, 164.47, 154.09, 135.05, 129.95, 129.55, 126.44, 125.27, 123.20,
121.63, 116.18; MS (EI, m/z): 229 [M+].
2-(3-fluorophenyl)benzothiazole[3] (f)
F
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), yellow solid.
1
H NMR (400 MHz, CDCl3): 8.12(d, J = 8.1 Hz, 1H), 7.81-8.00(m, 3H), 7.38 – 7.60
(m, 3H), 7.22 (ddd, J = 12.2, 8.0, 3.9 Hz, 1H); 13C NMR (100 MHz, CDCl3): 166.51,
164.28, 161.82, 153.88, 135.66, 135.05, 130.68, 126.56, 125.58, 123.33,121.69,
117.98, 117.77, 114.46, 114.22; MS (EI, m/z): 229 [M+].
2-(2-Fluorophenyl)benzothiazole[3] (g)
F
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.43-8.47(t, J = 7.6 Hz, 1H), 8.14-8.16(d, J = 8.0Hz,
1H), 7.97-7.99(d, J = 8.0 Hz, 2H), 7.43-7.55(m, 3H), 7.34-7.36(t, J = 7.6 Hz, 1H),
7.28-7.33(m, 1H); 13C NMR (100 MHz, CDCl3):161.82, 152.54, 132.19, 132.11,
131.30, 129.75, 126.32, 125.31, 124.72, 124.69, 123.29, 121.48, 116.51, 116.29; MS
(EI, m/z): 229 [M+].
2-(4-Chlorophenyl)benzothiazole[1] (h)
3
N
Cl
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.05-8.11(m, 3H), 7.93-7.95(d, J = 8.2 Hz, 1H),
7.51-7.55(m, 3H), 7.41-7.49(t, J = 7.4 Hz, 1H); 13C NMR (100 MHz, CDCl3): 166.64,
154.05, 137.05, 135.05, 132.11, 129.29, 128.73, 126.50, 125.43, 123.30, 121.67; MS
(EI, m/z): 245.5 [M+].
2-(2-Chlorophenyl)benzothiazole [1] (i)
Cl
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), colorless
solid.
1
H NMR (400 MHz, CDCl3): 8.23-8.26(m, 1H), 8.15-8.17(d, J = 8.0 Hz, 1H), 7.97(d,
J = 8.0 Hz, 1H), 7.54-7.58(m, 2H), 7.43-7.48(m, 3H); 13C NMR (100 MHz, CDCl3):
164.19, 152.52, 136.12, 132.73, 132.30, 131.77, 131.16, 130.82, 127.13, 126.30,
125.45, 123.48, 121.41; MS (EI, m/z): 245.5 [M+].
2-(4-Trifluoromethylphenyl)benzothiazole[3] (j)
N
CF3
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.21-8.23(d, J = 8.3Hz, 2H), 8.12-8.12(d, J = 8.1Hz,
1H), 7.94-7.96(d, J = 8.0 Hz, 1H), 7.76-7.78(d, J = 8.3 Hz, 2H), 7.53-7.57(m, 1H),
7.43-7.47(m, 1H); 13C NMR (100 MHz, CDCl3):166.05, 154.02, 136.75, 135.20,
132.62, 132.29, 127.77, 126.67, 126.07, 126.03, 125.99, 125.95, 125.80, 125.17,
123.63, 122.47, 121.75; MS (EI, m/z): 279 [M+].
2-Phenylbenzothiazole[1] (k)
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.11-8.15(m, 3H), 7.92-7.94(d, J = 8.0 Hz, 1H),
7.51-7.55(m, 4H), 7.39-7.44(t, J = 8.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): 168.08,
154.15, 135.08, 133.63, 130.99, 129.04, 127.58, 126.34, 125.21, 123.25, 121.65; MS
(EI, m/z): 211 [M+].
6-methyl-2-phenylbenzothiazole[1] (l)
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.09-8.12(m, 2H), 7.97-7.99(d, J = 8.3 Hz, 1H), 7.72(s,
1H), 7.50-7.52(m, 3H), 7.28-7.34(m, 1H), 2.53(s, 3H); 13C NMR (100 MHz, CDCl3):
4
167.03, 152.24, 135.38, 135.21, 133.73, 130.78, 129.00, 127.94, 127.43, 122.71,
121.39, 21.59; MS (EI, m/z): 225 [M+].
4,6-dimethyl-2-phenylbenzothiazole[1] (m)
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.11-8.14(m, 2H), 7.49-7.55(m, 4H), 7.14(s, 1H), 2.80(s,
3H), 2.48(s, 3H). 13C NMR (100 MHz, CDCl3): 165.56, 151.68, 135.16, 134.09,
132.75, 130.51, 128.92, 128.49, 127.39, 118.75, 21.55, 18.36; MS (EI, m/z): 239
[M+].
5-Fluoro-2-phenylbenzothiazole[1] (n)
F
N
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.08-8.11(m, 2H), 7.79(m, 2H), 7.53(m, 3H),
7.15-7.20(m, 1H); 13C NMR (100 MHz, CDCl3): 170.55, 163.15, 160.73, 155.10,
154.98, 133.36, 131.29, 130.44, 129.10, 127.54, 122.33, 122.23, 114.00, 113.75,
109.48, 109.24; MS (EI, m/z): 229 [M+].
6-Fluoro-2-phenylbenzothiazole[1] (o)
N
F
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.02-8.09(m, 3H), 7.59-7.62(dd, J = 8.1, 2.4 Hz, 1H),
7.51-7.53(m, 3H), 7.23-7.29(m, 1H). 13C NMR (100 MHz, CDCl3): 167.82, 161.71,
159.27, 150.77, 136.09, 133.35, 131.07, 129.10, 127.45, 124.18, 124.09, 115.10,
114.86, 108.00, 107.73; MS (EI, m/z): 229 [M+].
6-Chloro-2-phenylbenzothiazole[4] (p)
N
S
Cl
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
1
H NMR (400 MHz, CDCl3): 8.01-8.11(m, 2H), 7.98(d, J = 8.8 Hz, 1H), 7.90(s, 1H),
7.46-7.53(m, 4H); 13C NMR (100 MHz, CDCl3): 168.56, 152.68, 136.22, 133.21,
131.27, 131.07, 129.11, 127.55, 127.15, 123.94, 121.25; MS (EI, m/z): 245.5 [M+].
5-Fluoro-2-(3,4-dimethoxyphenyl)benzothiazole[1] (q)
OCH3
F
N
OCH3
S
Purified by flash chromatography (petroleum ether/ethyl acetate 100:1), white solid.
5
H NMR (400 MHz, CDCl3): 7.80 (dd, J = 8.8, 5.1 Hz, 1H), 7.75 – 7.69 (m, 2H), 7.60
(dd, J = 8.4, 1.9 Hz, 1H), 7.15 (d, J = 2.4 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 4.04 (s,
3H), 3.98 (s, 3H); 13C NMR (100 MHz, CDCl3): 170.39, 163.14, 160.72, 155.11,
151.81, 149.36, 130.25, 126.39, 122.15, 122.05, 121.19, 113.57, 113.32, 111.01,
109.71, 109.12, 108.89, 56.14, 56.07; MS (EI, m/z): 289 [M+].
1
References:
[1] H. Deng, Z.-K. Li, F. Ke, X.-G. Zhou, Chemistry - A European Journal. 2012,
18(16), 4840-4843.
[2] Y.-H. Cho, C.-Y. Lee, C.-H. Cheon, Tetrahedron. 2013, 69, 6565-6573.
[3] Q.-L. Song, Q. Feng, M.-X. Zhou, Org. Lett. 2013, 15 (23), 5990–5993.
[4] Y.-F. Liao, H.-R. Qi, S.-P. Chen, P.-C. Jiang, W. Zhou, G.-J. Deng, Org. Lett.
2012, 14 (23), 6004–6007.
6
2-(4-Methoxyphenyl)benzothiazole (a)
7
2-(3-Methoxyphenyl)benzothiazole (b)
8
2-(2-Methoxyphenyl)benzothiazole (c)
9
2-(3,4-dimethoxyphenyl)benzothiazole (d)
10
2-(4-Fluorophenyl)benzothiazole (e)
11
2-(3-fluorophenyl)benzothiazole (f)
12
2-(2-Fluorophenyl)benzothiazole (g)
13
2-(4-Chlorophenyl)benzothiazole (h)
14
2-(2-Chlorophenyl)benzothiazole (i)
15
2-(4-Trifluoromethylphenyl)benzothiazole (j)
16
2-Phenylbenzothiazole (k)
17
6-methyl-2-phenylbenzothiazole (l)
18
4,6-dimethyl-2-phenylbenzothiazole (m)
19
5-Fluoro-2-phenylbenzothiazole (n)
20
6-Fluoro-2-phenylbenzothiazole (o)
21
6-Chloro-2-phenylbenzothiazole (p)
22
5-Fluoro-2-(3,4-dimethoxyphenyl)benzothiazole (q)
23