Convenient synthesis of 2-arylbenzothiazoles and 2-arylnaphthothiazoles

Article abstract of DOI:10.1016/j.cclet.2011.12.004

Thiazoles including five 2-arylbenzothiazoles and two 2- arylnaphthothiazoles were synthesized using a simple synthetic strategy in this work. 2-Arylbenzothiazoles and 2-arylnaphthothiazoles can be prepared by the reaction of methylaromatics with aniline or naphthylamine in the presence of elemental sulfur, respectively. All the seven thiazoles were characterized by the melting point measurement, FTIR, ¹H NMR, ¹³C NMR and GC-MS analysis.

Full text of DOI:10.1016/j.cclet.2011.12.004

Available online at www.sciencedirect.com
Chinese Chemical Letters 23 (2012) 281–284
www.elsevier.com/locate/cclet
Convenient synthesis of 2-arylbenzothiazoles and
2-arylnaphthothiazoles
*
Li Fang Zhang, Zhong Hai Ni , Dong Ying Li, Zhi Hong Qin, Xian Yong Wei
*
School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou 221116, China
Received 9 October 2011
Available online 25 January 2012
Abstract
Thiazoles including five 2-arylbenzothiazoles and two 2-arylnaphthothiazoles were synthesized using a simple synthetic
strategy in this work. 2-Arylbenzothiazoles and 2-arylnaphthothiazoles can be prepared by the reaction of methylaromatics with
aniline or naphthylamine in the presence of elemental sulfur, respectively. All the seven thiazoles were characterized by the melting
1
point measurement, FTIR, H NMR, 13C NMR and GC–MS analysis.
# 2011 Zhong Hai Ni. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Thiazoles; Synthesis; Methylaromatics; Arylamines; Sulfur
The design, synthesis and property of thiazoles as a class of the most important heterocyclic systems have been
paid extensive and continuous attention in the fields of industry, agriculture and pharmacy [1–3]. For example,
2-arylbenzothiazoles play significant role in medicine as imaging agents for b-amyloid, antitumoragents, antituberculotics,
antiparasitics and calcium channel antagonists [4–6], and in chemical detection as chemiluminescent agents and
photosensitizers [7,8], and naphthothiazoles found their merits in antitumor [9] or sensitizer dye [10].
Up to date, many synthetic strategies have been developed for the synthesis of 2-arylbenzothiazoles, among which
the ways starting from 2-aminothiophenol [11–19] and N-phenyl thioamide [20–23] are the most common methods.
Other reasonable and effective methods include condensation of copper(I) thiobenzoates and 2-iodoanilines [24],
conversion from other heterocycles [25,26] and Suzuki coupling of 2-bromobenzothiazole with aryl boronic acids [4].
There is also the approach involving sulfur [27,28], which is in time out of mind and was not investigated deeply.
Generally, these methods usually employ expensive starting materials or special catalysts, or require multistep
synthetic process. Therefore, the convenient method of 2-arylbenzothiazoles would be favorable.
In the present work, we report the convenient synthesis of a series of 2-arylbenzothiazoles and 2-arylnaphthothiazoles
(Scheme 1) using available and cheap starting materials methylaromatics, arylanilines and sulfur.
As shown in Table 1, 2-arylbenzothiazoles and 2-arylnaphthothiazoles can be formed from the reaction of
methylaromatics and aniline or naphthylaniline with sulfur (Scheme 1). In this reaction, thiazole cycle was formed
from three facile chemical materials in the absence of any catalyst [29]. The employed methylaromatics include
toluene, p-xylene, 1-methylnaphthalene and p-methylphenol. At low temperatures, the reactions proceeded
* Corresponding authors.
E-mail addresses: nizhonghai@cumt.edu.cn (Z.H. Ni), wei_xianyong@163.com (X.Y. Wei).
1001-8417/$ – see front matter # 2011 Zhong Hai Ni. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2011.12.004

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L.F. Zhang et al. / Chinese Chemical Letters 23 (2012) 281–284
N
S
R1
R1 CH3
+
NH2
S
1-3
R1 = Ph, 1'-Naphthyl or 4-OH-Ph
N
S
H3C
S
4a
H3C
CH3
+
NH2
+
N
S
N
S
4b
NH2
N
S
S
R2 CH3
+
R1
5 or 6
R2 = Ph or 4-CH3-Ph
Scheme 1. Synthesis of the title compounds.
Table 1
Results and conditions of the reaction of methylaromatics with arylamines in the presence of sulfur.a
Reactant
Temperature (8C)
Time (h)
Product
Yield (%)
Toluene, aniline
275
275
275
275
3.5
0.5
0.5
3.5
1
74
42
62
61
14
15
70
50
41
1-Methylnaphthalene, aniline
p-Methylphenol, aniline
p-Xylene, aniline
2
3
4a
4b
4a
4b
5
p-Xylene, anilineb
275
3.5
Toluene, 1-naphthylamine
275
250
3.5
1.5
p-Xylene, 1-naphthylamine
6
a
Arene:arylamine:sulfur (mol ratio) = 1:1:4.
b
Arene:arylamine:sulfur (mol ratio) = 1:2:8.
insignificantly, affording target products in low yields, but at high-temperature reactions tended to produce more
byproducts. Optimum temperature was determined to be 275 8C.
For mono-methylaromatics, there is only one expected products (1–3) [30] with reasonable yields. However, if
there are two methyl groups on the aromatics, there will be two possible products with one or two benzothiazole
segment(s) whose yields are determined by the ratio of the materials. For p-xylene, when less aniline and sulfur were
provided with mol ratio of p-xylene:arylamine:sulfur = 1:1:4, compounds 4a [31] or 6 containing one benzothiazole
segment were obtained as the dominating products; and when, there were enough aniline and sulfur, namely, the ratio
of arene:arylamine:sulfur (mol ratio) = 1:2:8, compound 4b [31] with two benzothiazole segments are the main
product.
Besides aniline, 1-naphthylamine was also introduced for the synthesis of 2-arylnaphthothiazoles. Toluene and p-
xylene were adopted to react with 1-naphthylamine, giving the expected products 5 and 6 [32] with relative lower
yields than those of 2-arylbenzothiazoles.
In conclusion, a series of thiazoles including five 2-arylbenzothiazoles and two 2-arylnaphthothiazoles were
conveniently synthesized by the reaction of methylaromatics with aniline or naphthylamine in the presence of
elementary sulfur. The products were characterized by various means. Further and detailed study of relevant work will
be carried out.
Acknowledgments
The authors are grateful for the research support from National Basic Research Program of China (973 Program,
No. 2012CB214900), the National Natural Science Foundation of China (No. 21176246) and the Fundamental
Research Funds for the Central Universities.

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[29] General synthesis for 2-arylbenzothiazoles and 2-arylnaphthothiazoles: Methylaromatics (50.0 mmol), aniline or 1-naphthylamine
(50.0 mmol) and sulfur (200.0 mmol) were put into a 50.0 mL autoclave. The air in the autoclave was replaced several times with nitrogen,
then the autoclave was heated to the set temperature and kept at that temperature for 0.5, 1.5 or 3.5 h. Finally, the autoclave was cooled to room
temperature and the resulted mixture was analyzed by GC instrument. The result brown mixture was distilled under reduced pressure to give
three distillates.
[30] The purification procedures and spectral data for compounds 1–3. 2-Phenylbenzothiazole (1): The yellow intermediate distillated was
1
recrystallized in methanol for four times, giving pale yellow needles. mp 113.5ꢀ114.0 8C (115.0 8C [11]). H NMR (500 MHz, CDCl3): d
7.36ꢀ7.39 (t, 1 H, J = 7.5 Hz), 7.47ꢀ7.49 (m, 4 H), 7.89ꢀ7.90 (d, 1 H, J = 8.0 Hz), 8.05ꢀ8.09 (m, 3 H). 13C NMR (125 MHz, CDCl3): d 168.1,
154.2, 135.1, 133.7, 131.0, 129.0, 127.6, 126.3, 125.2, 123.3, 121.6. FTIR: 3063, 1510, 1479, 1433, 1313, 1225, 1070, 964, 764, 731, 690,
623 cmꢀ1. MS: m/z (%) 212 (33, (M+1)+), 211 (100, M+), 210 (43), 108 (42), 82 (15), 69 (27). 2-(10-Naphthyl)benzothiazole (2): The
intermediate distillate was purified by chromatography (silica gel, 100–200 mesh, eluted with petroleum ether to eliminate the impurity and
secondly with acetone) and recrystallization from the mixture solvent of petroleum ether and acetone for three times to give fawn crystal of 2.
mp 78.5–79.5 8C. 1H NMR (500 MHz, CDCl3): d 7.43–7.46 (t (d, d, d), 1 H, J = 7.5, 1.0 Hz), 7.53–7.57 (m, 3 H), 7.59–7.63 (t (d, t, d), 1 H,
J = 7.5, 1.5 Hz), 7.91–7.93 (t (d, s, s), 2 H, J = 7.5 Hz), 7.95–7.99 (t, 2 H, J = 8.5 Hz), 8.18–8.20 (d, 1 H, J = 8.5 Hz), 8.91–8.930 (d, 1 H,
J = 8.5 Hz). 13C NMR (125 MHz, CDCl3): d 167.6, 154.2, 135.5, 134.0, 131.1, 130.9, 130.7, 129.4, 128.4, 127.6, 126.5, 126.3, 125.9, 125.3,
125.0, 123.6, 121.4. FTIR: 3045, 1506, 1458, 1429, 1306, 1230, 1176, 1096, 933, 802, 768, 733, 694 cmꢀ1. MS: m/z (%) 262 (22, (M+1)+), 261
(78, M+), 260 (100), 130 (21), 69 (12). 2-p-Hydroxyphenylbenzothiazole (3): The intermediate distillated was dissolved in hot acetone,
deleting impurity by filtration, the pale yellow flaky crystals was obtained when cooling the filtrate. mp 234.5–235.5 8C. 1H NMR (500 MHz,
CDCl3): d 2.87 (s, 1 H), 6.99–7.02 (d (t, t), 2 H, J = 9.0, 2.0 Hz), 7.37–7.40 (t (d, d, d), 1 H, J = 7.5, 1.0 Hz), 7.47–7.51 (t (d, d, d), 1 H, J = 7.5,
1.0 Hz), 7.95–8.02 (m, 4 H). 13C NMR (125 MHz, CDCl3): d 168.4, 161.2, 155.3, 135.6, 130.0, 127.1, 126.3, 125.7, 123.4, 122.6, 116.8. FTIR:
3057, 1605, 1483, 1433, 1283, 1225, 1163, 978, 830, 756, 723 cmꢀ1. MS: m/z (%) 228 (16, (M+1)+), 227 (100, M+), 198 (10), 108 (18), 69 (16).
[31] The purification procedures and spectral data for compounds 2-p-methylphenylbenzothiazole (4a) and 1, 4-bi(2,20-benzothiazolyl)benzene
(4b). The intermediate distillate was purified in the way of 1 to give 4a as pale yellow needles, and the heavy distillate was washed with
petroleum ether and methanol for times and give yellow powder of 4b. The melting point of 4b was not observed for there was a wide melting
range of 240–268 8C which may be explained by decomposition according to a previous report [1]. 4a: mp 83.5–85.0 8C (85.0–85.5 8C [14]).
1H NMR (500 MHz, CDCl3): d 2.41 (s, 3 H), 7.27–7.29 (d, 2 H, J = 8.0 Hz), 7.37–7.37 (t (d, s, d), 1 H, J = 7.5, 1.0 Hz), 7.45–7.48 (t (d, d, d), 1
H, J = 7.5, 1 Hz), 7.87–7.88 (d (d, d), 1 H, J = 8.0, 0.5 Hz), 7.96–7.98 (d, 2 H, J = 8.0 Hz), 8.03–8.05 (d, 1 H, J = 8.0 Hz). 13C NMR (125 MHz,
CDCl3): d 168.2, 154.2, 141.4, 135.0, 131.0, 129.7, 127.5, 126.2, 125.0, 123.1, 121.5, 21.5. FTIR: 3057, 3024, 2914, 1608, 1483, 1313, 1228,
1184, 962, 820, 759, 731, 625 cmꢀ1. MS: m/z (%) 226 (20, (M+1)+), 225 (100, M+), 224 (42), 69 (12). 4b: 1H NMR (500 MHz, DMSO-d6): d
7.51–7.54 (m, 2 H), 7.59–7.62 (m, 2 H), 8.13–8.14 (d, 2 H, J = 8.0 Hz), 8.21–8.22 (d, 2 H, J = 7.5 Hz), 8.32 (s, 4 H). 13C NMR (125 MHz,
DMSO-d6): d 166.1, 153.5, 135.0, 134.6, 128.1, 126.8, 125.9, 123.1, 122.4. FTIR: 3055, 1497, 1477, 1433, 1404, 1313, 1250, 1223, 1113, 964,
843, 748, 725, 682, 623 cmꢀ1. MS: m/z (%) 345 (25, (M+1)+), 344 (100, M+), 343 (13), 108 (29), 82 (14), 69 (22).

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[32] The purification procedures and spectral data for compounds 2-phenylnaphtho[1,2-d]thiazole (5) and 2-p-methylphenyl-naphtho[1,2-
d]thiazole (6). 5: The intermediate distillate was leached with hot methanol for three times, and the filtrate was evaporated and the residue
was recrystallized from mixed solvent of methanol and tetrahydrofuran (vol ratio about 5:1) to give grey needles. mp 99.5–101.0 8C. 1H NMR
(500 MHz, CDCl3): d 7.47–7.53 (m, 3 H), 7.56–7.59 (t (d, d, d), 1 H, J = 7.5, 1.0 Hz), 7.66–7.69 (t (d, s, d), 1 H, J = 7.5, 1.0 Hz), 7.78–7.80 (d, 1
H, J = 8.5 Hz), 7.89–7.91 (d, 1 H, J = 9.0 Hz), 7.93–7.95 (d, 1 H, J = 8.0 Hz), 8.17–8.20 (d (d, d), 2 H, J = 8.0, 1.5 Hz), 8.90–8.92 (d, 1 H,
J = 8.0 Hz). 13C NMR (125 MHz, CDCl3): d 167.1, 150.5, 134.0, 132.1, 131.7, 130.6, 129.0, 128.8, 128.1, 127.3, 126.9, 126.1, 125.9, 124.0,
119.0. FTIR: 3048, 1510, 1473, 1443, 1363, 1252, 1070, 972, 906, 797, 758, 738, 681, 605 cmꢀ1. MS: m/z (%) 262 (20, (M+1)+), 261 (100,
M+), 158 (29), 114 (19). 6: The intermediate distillate was dissolved in tetrahydrofuran, filtrated and evaporated. The residue was re-
crystallized from mixed solvent of methanol and tetrahydrofuran (vol ratio about 4:1) to give pale green needles. mp 97.0–98.5 8C. 1H NMR
(500 MHz, CDCl3): d 2.43 (s, 3 H), 7.30–7.31 (d, 2 H, J = 8.0 Hz), 7.55–7.58 (t (d, s, d), 1 H, J = 7.5, 1.0 Hz), 7.65–7.68 (t (d, s, d), 1 H, J = 7.5,
1.0 Hz), 7.77–7.79 (d, 1 H, J = 9.0 Hz), 7.88–7.90 (d, 1 H, J = 8.5 Hz), 7.92–7.94 (d, 1 H, J = 8.0 Hz), 8.06–8.08 (d, 2 H, J = 8.0 Hz), 8.89–8.90
(d, 1 H, J = 8.0 Hz). 13C NMR (125 MHz, CDCl3): d 167.3, 150.5, 141.0, 132.1, 131.5, 131.4, 129.7, 128.8, 128.0, 127.3, 126.9, 126.0, 125.7,
124.1, 119.0, 21.5. FTIR: 3051, 2916, 1502, 1473, 1363, 1240, 1178, 1080, 972, 906, 802, 739, 690 cmꢀ1. MS: m/z (%) 276 (22, (M+1)+), 275
(100, M+), 274 (15), 158 (15), 114 (14).