Samarium(III) triflate: A new catalyst for facile synthesis of benzothiazoles and benzoxazoles from carboxylic acids in aqueous media

Article abstract of DOI:10.1007/s11164-014-1897-x

A facile synthetic method for benzothiazoles and benzoxazoles comprising the reaction of corresponding 2-aminothiophenol and 2-aminophenol with various substituted aromatic carboxylic acids using Samarium(III) triflate as a catalyst has been described. The advantages of the method are short reaction times and aqueous reaction media and easy work-up. The catalysts can be recovered for the subsequent reactions and reused without any appreciable loss of efficiency.

Full text of DOI:10.1007/s11164-014-1897-x

Res Chem Intermed
DOI 10.1007/s11164-014-1897-x
Samarium(III) triflate: a new catalyst for facile
synthesis of benzothiazoles and benzoxazoles
from carboxylic acids in aqueous media
•
Pratapsinha B. Gorepatil Yogesh D. Mane
•
•
•
Amarsinha B. Gorepatil Mahadev V. Gaikwad
Vilas S. Ingle
Received: 9 October 2014 / Accepted: 10 December 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract A facile synthetic method for benzothiazoles and benzoxazoles com-
prising the reaction of corresponding 2-aminothiophenol and 2-aminophenol with
various substituted aromatic carboxylic acids using Samarium(III) triflate as a
catalyst has been described. The advantages of the method are short reaction times
and aqueous reaction media and easy work-up. The catalysts can be recovered for
the subsequent reactions and reused without any appreciable loss of efficiency.
Keywords Carboxylic acids Á Benzothiazoles Á Benzoxazoles Á Lewis acid Á
Samarium triflate
Introduction
Molecules containing benzothiazole and benzoxazole nucleus attract much interest
in diverse areas of chemistry. Benzothiazole derivatives are important for natural
products and pharmaceuticals that exhibit remarkable antitumor activities [1–4], and
they are also reported to exhibit diverse biological activities [5], with their many
derivatives acting as useful intermediates that find applications in medicinal
chemistry [6] and material science [7], particularly as sensors [8]. The benzoxazole
P. B. Gorepatil Á Y. D. Mane Á V. S. Ingle (&)
Department of Chemistry, S. C. S. College, Omerga, Dist-Osmanabad 413 606, India
e-mail: inglevilas71@yahoo.in
P. B. Gorepatil
e-mail: dr.pratapgorepatil@gmail.com
A. B. Gorepatil
Department of Chemistry, S. G. R. G. S. College, Paranda, Dist-Osmanabad, India
M. V. Gaikwad
Department of Chemistry, B. P. C. A. S. Angar, Dist-Solapur 413 214, India
123

P. B. Gorepatil et al.
moiety is a basic structural unit found in a wide class of natural products and
synthetic compounds showing biological properties, such as natural antimycobac-
terials [9], non-nucleoside reserve transcriptase inhibitors [10], cytotoxic natural
products [11], anticancer agents [12], and elastase inhibitors [13], and in the
agricultural field [14].
A number of methods have been reported for the synthesis of the benzothiazole
[15] by condensation of 2-aminophenol with acyl chlorides or aldehydes and also by
coupling with carboxylic acid derivatives or by oxidative cyclization of a phenolic
imine intermediate [16]. The first route requires strongly acidic conditions, high
temperatures, and long reaction times [17], whereas the second route requires strong
oxidants [16, 18]. Apart from cyclization reactions, 2-substituted benzoxazoles are
synthesized by amination, arylation and alkylation of the benzoxazoles, via metal-
catalyzed C–H bond activation [19–21].
Several synthetic methodologies have been developed for the synthesis of
2-substituted benzothiazoles [22]. Most of the synthetic approaches are based on the
condensation of 2-aminothiophenol with substituted nitriles [21], carboxylic acids
[23–27], acyl chlorides [28, 29] and esters [30], or with aldehydes followed by
oxidation by using various oxidative reagents and catalysts [31–43]. Some
benzothiazoles and benzoxazoles are also synthesized by cyclocondensation with
b-diketones using Bronsted acid [44, 45]. Although these methods are suitable for
specific synthetic conditions, most of these methods suffer from one or more
disadvantages such as long reaction times, expensive reagents, drastic reaction
conditions, low yields, tedious work-up procedures and co-occurrence of several
side reactions.
Recently, with the objective of developing new environmentally benign reaction
conditions and media for organic reactions with excellent efficiency and selectivity,
water has been shown to be a useful solvent for certain Lewis acids [46]. For
instance, In(OTf)3, Yb(OTf)3, Bi(OTf)3, Sc(OTf)3, Sm(OTf)3, and other metal
triflates have been found to be water-tolerant, reusable Lewis acids catalysts and
have received considerable interest for condensation reactions [47] and other
organic transformations [48–50].
In continuation of seeking newer synthetic routes for 1,3-azole derivatives [51],
we report the use of samarium triflate as a water-tolerant Lewis acid catalyst for the
synthesis of 2-substituted benzoxazoles and benzothiazoles by the condensation of
2-aminophenols or 2-aminothiophenols with carboxylic acids in ethanol:water, as
shown in Scheme 1.
Scheme1 Samarium triflate [Sm(OTf3)] catalyzed synthesis of 2-substituted benzoxazoles and benzothiazoles
123

A new catalyst for facile synthesis of benzothiazoles and benzoxazoles
Experimental
All commercial reagents and solvents were used without further purification.
Analytical thin layer chromatography (TLC) was carried out using silica gel 60 F254
pre-coated plates. Column chromatography was carried out using silica gel (60–120
1
mesh size). Visualization was accomplished with UV lamp, I2 stain. H and 13C
NMR were recorded on 300 and 75 MHz, respectively, in DMSO-d6 using TMS as
the internal standard. Chemical shifts were reported in parts per million (ppm)
downfield from TMS. IR spectra were obtained using a Bruker FT-IR spectropho-
tometer. Melting points were determined with a capillary apparatus and were not
further corrected.
General procedure for the synthesis of benzoxazoles/benzothiazole
To a mixture of o-aminophenol/o-aminothiophenol (1 mmol) and carboxylic acids
(1 mmol) in ethanol:water (2:2 mL) under open atmosphere, 10 mol% of samarium
triflate catalyst were added. The resulting mixture was stirred at 80 °C. After
completion of the reaction, as monitored by TLC, the reaction mixture was diluted
with 1:1 mixture of water/ethyl acetate (10 mL) and catalyst recovered by simple
filtration. The reaction mixture was extracted with diethyl ether (2 9 10 mL) and
dried with anhydrous sodium sulfate. Finally, crude product was recrystallized from
ethyl acetate or methanol. All the pure products were confirmed by their 1 HNMR,
13C NMR, IR, and mass spectroscopy data.
Spectral data for selected compounds
1. 2-(4-Nitrophenyl)benzo[d]thiazole (Table 2, entry b) Mp 225–227 °C; 1H NMR
(300 MHz, DMSO-d6): d 7.51–7.62 (d, 2H), 7.60–7.68 (m, 1H), 8.01–8.07 (d,
2H), 8.16–8.76 (m, 1H), 8.36–8.52(m, 2H). 13C NMR (75 MHz, DMSO-d6): d
121.9, 123.8, 124.4, 126.1, 126.8, 128.2, 135.6, 139.2, 149.0, 154.1, 165.0., EI
MS (m/z): 256.9 (M?).
1
2. 2-(4-Methoxyphenyl)benzo[d]thiazole (Table 2, entry e) Mp 122–124 °C; H
NMR (300 MHz, DMSO-d6): d 3.89 (s, 3H), 7.02–7.13 (d, 2H), 7.39–7.47 (m,
1H), 7.51–7.60 (d, 2H), 7.94–8.15 (d, 1H), 8.06–8.20 (m, 2H). 13C NMR
(75 MHz, DMSO-d6): d 55.4, 114.3, 121.6, 122.7, 124.8, 126.2, 126.4, 129.0,
135.0, 154.3, 162.0, 167.7., EI MS (m/z): 241.9 (M?).
1
3. 2-(Pyridin-4-yl)benzo[d]thiazole (Table 2, entry h) Mp 130–132 °C; H NMR
(300 MHz, DMSO-d6): d 7.44–7.50 (d, 2H), 7.57–7.68 (m, 1H), 8.01–8.11 (d,
2H), 8.13–8.53 (m, 1H), 8.40–8.56 (m, 2H). 13C NMR (75 MHz, DMSO-d6): d
121.8, 123.3, 123.8, 125.6, 126.6, 129.6, 134.4, 135.1, 148.5, 151.6, 154.0,
164.7., EI MS (m/z): 212.9 (M?).
4. 2-Phenylbenzo[d]oxazole (Table 2, entry i) Mp 100–102 °C; 1H NMR
(300 MHz, DMSO-d6): d 7.39-7.43 (m, 5H), 7.57-7.63 (m, 4H). 13C NMR
(75 MHz, DMSO-d6): d 110.6, 119.9, 124.5, 125.1, 127.3, 127.5, 128.9, 131.5,
142.2, 150.8, 163.0., EI MS (m/z): 195.9 (M?).
123

P. B. Gorepatil et al.
5. 2-(4-Methylphenyl)benzo[d]oxazole (Table 2, entry j) Mp 114–116 °C; 1H
NMR (300 MHz, DMSO-d6): d 2.45 (s, 3H), 7.36–7.46 (d, 2H), 7.41–7.49 (m,
1H), 7.51–7.60 (d, 2H), 7.96–8.46 (m, 1H), 8.00–8.16 (m, 2H). 13C NMR
(75 MHz, DMSO-d6): d 21.2, 121.6, 122.9, 125.0, 126.2, 127.3, 129.7, 131.0,
135.0, 141.6, 154.2, 168.0., EI MS (m/z): 209.9 (M?).
6. 2-(4-Chlorophenyl)benzo[d]oxazole (Table 2, entry k) Mp 147–149 °C; 1H
NMR (300 MHz, DMSO-d6): d 7.44–7.55 (d, 2H), 7.50–7.58 (m, 1H),
7.90–7.97 (d, 2H), 8.05–8.09 (m, 1H), 8.11–8.19 (m, 2H). 13C NMR
(75 MHz, DMSO-d6): d 121.7, 123.2, 125.4, 126.5, 128.7, 129.2, 132.2,
135.1, 136.8, 154.1, 166.5., EI MS (m/z): 231.9 (M?).
Results and discussion
In order to find the best experimental conditions, the cyclocondensation between
equimolar quantities of benzoic acid and 2-aminothiophenol, carried in the presence of
samarium triflate, was considered as the standard model reaction. To evaluate the effect of
the solvents, the model reaction was run in different solvents, namely ethanol,
ethanol:water, 1,4-dioxane, acetonitrile, and toluene. To examine the catalytic efficiency
of samarium triflate, the model reaction was then run in ethanol in the absence of a catalyst.
There was only 35 % conversion after 8 h (Table 1, entry a). The use of ethanol as solvent
gave poor yields in the presence of 5 mol% of catalyst (Table 1, entryb). Solventslike 1,4-
dioxane, acetonitrile, and toluene gave moderate yields (Table 1, entries f–i). When the
reaction was run in an equimolar amount of ethanol:water, the yield of benzothiazole was
found to be relatively better (Table 1, entry e). Therefore, ethanol:water was selected as
Table 1 Optimization of reaction conditions for the synthesis of 2-Phenylbenzothiazole
Entry
Catalyst (mol%)
Solvents
Time (h)
Yield (%)a
a
b
c
d
e
f
No catalyst
EtOH
8
2
4
3
2
4
4
5
5
35
70
74
86
89
63
65
76
86
Sm(OTf)3 (5 mol%)
Sm(OTf)3 (2 mol%)
Sm(OTf)3 (5 mol%)
Sm(OTf)3 (10 mol%)
Sm(OTf)3 (5 mol%)
Sm(OTf)3 (5 mol%)
Sm(OTf)3 (5 mol%)
Sm(OTf)3 (10 mol%)
EtOH
EtOH/H2O (2:2)
EtOH/H2O (2:2)
EtOH/H2O (2:2)
CH3CN
g
h
i
Dioxane
Toluene
Toluene
Stirring at 80 °C. Bold row is the standard optimisation condition
a
Isolated yield
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A new catalyst for facile synthesis of benzothiazoles and benzoxazoles
Table 2 Sm(OTf)3-catalyzed synthesis of 2-substituted benzothiazoles and benzoxazoles
Entry
a
Products
Yielda (%)
Time (h)
2
M.P.b (°C)
89
113–115
b
c
92
92
3
3
230–232
96–98
d
e
f
74
72
88
82
85
88
86
90
92
84
85
5
4
3
4
5
3
4
3
4
4
4
224–226
120–122
130–132
115–117
130–132
102–104
112–114
148–150
170–172
104–106
282–284
g
h
i
j
k
l
m
n
123

P. B. Gorepatil et al.
Table 2 continued
Entry
o
Products
Yielda (%)
72
Time (h)
M.P.b (°C)
5
170–172
p
94
3
192–194
q
r
84
90
4
4
150–152
145–147
Reaction conditions: carboxylic acids (1 mmol), 2-aminothiophenol/2-aminophenol (1 mmol), Sm(OTf)3
(10 mol%), EtOH-H2O (2:2 mL), stirring at 80 °C
a
Isolated yield
b
M.P. melting point
the solvent for this reaction and, in order to evaluate the reactivities of the different starting
materials, the cyclization process was always conducted by heating to 80 °C. We carried
out the same reaction using 10 mol% of samarium triflate at room temperature, but it gave
a very low yield even with a longer reaction time.
After optimization, we extended the study to various 2-aminothiophenol and
2-aminophenol with aliphatic, aromatic and heteroaromatic carboxylic acids. In
general, most of the reactions proceed very smoothly to give the corresponding
2-substituted benzothiazoles and benzoxazoles in moderate to excellent yields. We
have also studied the electronic factor, and we assumed that electron-deficient
carboxylic acids gave better yields in shorter reaction times as compared to
electron-rich acids. The results are summarized in Table 2.
Here, for the first time, samarium triflate has been successfully employed to
catalyze the condensation of 2-aminothiophenol/2-aminophenol and carboxylic
acids in ethanol:water (2:2 mL) to yield 2-substituted benzothiazoles/benzoxazoles
in moderate to good yields under mild reaction conditions. This protocol is user
friendly and could be an attractive tool for the synthesis of highly functionalized
bioactive benzothiazoles and benzoxazoles.
Another advantage of this method is catalytic reusability or recovery: the catalyst
was removed by simple filtration, treated with ethanol and filtered. The catalyst was
then dried at 100 °C for 1 h and could be reused for a second reaction. It was found
that the catalytic activities of the recovered catalyst were almost the same as that of
the fresh catalyst (Table 3).
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A new catalyst for facile synthesis of benzothiazoles and benzoxazoles
Table 3 Catalyst reusability study for the reaction of benzoic acid with 2-aminothiophenol
Entry
Yield (%)a
Catalyst
recovery (%)
a
b
c
d
89
86
82
78
94
92
88
86
Reaction conditions: benzoicacid (1 mmol), 2-aminothiophenol (1 mmol), Sm(OTf)3 (10 mol%), EtOH-
H2O (2:2 mL), 80 °C
a
Isolated yield
Conclusion
In conclusion, a one-pot methodology has been developed for the synthesis of
benzothiazole and benzoxazoles catalyzed by samarium triflate. Compared to
previously reported methods, this method as mild reaction conditions, clean
reaction, cost efficiency, easy work-up, easy recovery and reusability of the catalyst.
Acknowledgment One of the authors, Mr. P.B. Gorepatil, is grateful to the Council of Scientific and
Industrial Research (CSIR), New Delhi for a Junior Research Fellowship (JRF).
References
1. I. Hutchinson, M.S. Chua, H.L. Browne, V. Trapani, T.D. Bradshaw, A.D. Westwell, M.F. Stevens, J.
Med. Chem. 44, 1446 (2001)
2. S. Aiello, G. Wells, E.L. Stone, H. Kadri, R. Bazzi, D.R. Bell, M.F. Stevens, C.S. Matthews, T.D.
Bradshaw, A.D. Westwell, J. Med. Chem. 51, 5135 (2008)
3. B.S. Tan, K.H. Tiong, A. Muruhadas, N. Randhawa, H.L. Hoo, T.D. Bradshaw, M.F. Stevens, O.
Leong, Mol. Cancer Ther. 10, 1982 (2011)
4. K. Wang, F.P. Guengerich, Chem. Res. Toxicol. 25, 1740 (2012)
5. K. Serdons, C. Terwinghe, P. Vermaelen, K. Van Laere, H. Kung, L. Mortelmans, G. Bormans, A.
Verbruggen, J. Med. Chem. 52, 1428 (2009)
6. P.S. Yadav, D. Devprakash, G.P. Senthilkumar, Int. J. Pharm. Sci. Drug. Res. 1, 01 (2011)
7. D. Li, H. Zhang, C. Wang, S. Huang, J. Guo, Y. Wang, J. Mater. Chem. 22, 4319 (2012)
8. R. Hu, J. Feng, D. Hu, S. Wang, S. Li, Y. Li, G. Yang, Angew. Chem. Int. Ed. 49, 4915 (2010)
9. J.P. Davidson, E.J. Corey, J. Am. Chem. Soc. 125, 13486 (2003)
10. J.A. Glober, G. Dornadula, M.R. Rice, A.L. Simcoe, D.J. Hazuda, M.D.J. Miller, J. Biol. Chem. 282,
8005 (2007)
11. M. Ueki, K. Ueno, S. Miyadoh, K. Abe, K. Shibata, M. Taniguchi, S. Oi, J. Antibiot. 46, 1089 (1993)
12. J. Jiang, X. Tang, W. Dou, H. Zhang, W. Liu, C. Wang, J. Zheng, J. Inorg. Biochem. 104, 583 (2010)
13. P.D. Edwards, M.A. Zottola, M. Davis, J. Williams, P.A. Tuthill, J. Med. Chem. 38, 3972 (1995)
14. A.B. Naidu, G. Sekar, Synthesis, 579 (2010)
15. I. Hutchinson, S.A. Jennings, B.R. Vishnuvajjala, A.D. West well, M.F.G. Stevens, J. Med. Chem.
45, 744 (2002)
16. A.R. Katritzky, C.A. Ramsden, E.F.V. Scriven, R.J.K. Taylor, Comprehensive Heterocyclic Chem-
istry III, (Elsevier, Oxford, 2008), Vol. 4, pp. 487–543
17. Y.H. So, J.P. Heeschen, J. Org. Chem. 62, 3552 (1997)
18. D.S. Bose, M. Idrees, Synthesis, 398 (2010)
19. M. Lamani, K.R. Prabhu, J. Org. Chem. 76, 7938 (2011)
123

P. B. Gorepatil et al.
20. A.J. Blacker, M.F. Mohamed, S.P. Marsden, O. Saidi, J.M.J. Williams, Tetrahedron Lett. 50, 6106
(2009)
21. R.-G. Xing, Y.-N. Li, Q. Liu, Q.-Y. Meng, J. Li, X.-X. Shen, Z. Liu, B. Zhou, X. Yao, Z.-L. Liu, Eur.
J. Org. Chem. 6627 (2010)
22. R.S. Pottorf, N.K. Chadha, M. Katkevics, V. Ozola, E. Suna, H. Ghane, T. Regberg, M.R. Player,
Tetrahedron Lett. 44, 175 (2003)
23. R.H. Tale, Org. Lett. 4, 1641 (2002)
24. S. Mourtas, D. Gatos, K. Barlos, Tetrahedron Lett. 42, 2201 (2001)
25. A.K. Chakraborti, C. Selvam, G. Kaur, S. Bhagat, Synlett, 851 (2004)
26. C.P. Chen, Y.J. Chen, Tetrahedron Lett. 45, 113 (2004)
27. J.A. Seijas, M.P. Vazquez-Tato, M.R. Carballido-Reboredo, J. Crecente-Campo, L. Romar-Lopez,
Synlett, 313 (2007)
28. I.R. Laskar, T.M. Chen, Chem. Mater. 16, 111 (2004)
29. R.N. Nadaf, S.A. Siddiqui, T. Daniel, R.J. Lahoti, K.V. Srinivasan, J. Mol. Catal. A: Chem. 214, 155
(2004)
30. H. Matsushita, S.H. Lee, M. Joung, B. Clapham, K.D. Janda, Tetrahedron Lett. 45, 313 (2004)
31. X.L. Yang, C.M. Xu, S.M. Lin, J.X. Chen, J.C. Ding, H.Y. Wu, W.K. Su, J. Braz. Chem. Soc. 21, 37
(2010)
32. K. Bahrami, M.M. Khodaei, F. Naali, J. Org. Chem. 73, 6835 (2008)
33. H.Y. Guo, J.C. Li, Y.L. Shang, Chin. Chem. Lett. 20, 1408 (2009)
34. M. Okimoto, T. Yoshida, M. Hoshi, K. Hattori, M. Komata, K. Tomozawa, T. Chiba, Heterocycles
75, 35 (2008)
35. A. Kumar, R.A. Maurya, P. Ahmad, J. Comb. Chem. 11, 198 (2009)
36. H.L. Xiao, J.X. Chen, M.C. Liu, D.J. Zhu, J.C. Ding, H.Y. Wu, Chem. Lett. 38, 170 (2009)
37. M. Abdollahi-Alibeik, S. Poorirani, Phosphorus, Sulfur Silicon Relat. Elem. 184, 3182 (2009)
38. M. Kodomari, Y. Tamaru, T. Aoyama, Synth. Commun. 34, 3029 (2004)
39. U.R. Pratap, J.R. Mali, D.V. Jawale, R.A. Mane, Tetrahedron Lett. 50, 1352 (2009)
40. K. Bahrami, M.M. Khodaei, A. Nejatia, Green Chem. 12, 1237 (2010)
41. A. Kumar, S. Sharma, R.A. Maurya, Tetrahedron Lett. 51, 6224 (2010)
42. S.V. Nalage, S.V. Bhosale, D.S. Bhosale, W.N. Jadhav, Chin. Chem. Lett. 21, 790 (2010)
43. H. Eshghi, M. Rahimizadeh, A. Shiri, P. Sedaghat, Bull. Korean Chem. Soc. 33, 515 (2012)
44. M.S. Mayo, X. Yu, X. Zhou, X. Feng, Y. Yamamoto, M. Bao, J. Org. Chem. 79, 6310 (2014)
45. M.S. Mayo, X. Yu, X. Zhou, X. Feng, Y. Yamamoto, M. Bao, Org. Lett. 16, 764 (2014)
46. C.-J. Li, B.M. Trost, Proc. Natl. Acad. Sci. USA 105, 13197 (2008)
47. A.V. Narsaiah, A.R. Reddy, J.S. Yadav, Synth. Commun. 41, 262 (2011)
48. S. Kobayashi, K. Manabe, Acc. Chem. Res. 35, 209 (2002)
49. A. Dzudza, T.J. Marks, J. Org. Chem. 73, 4004 (2008)
50. A.V. Narsaiah, A.R. Reddy, J.S. Yadav, Synth. Commun. 41, 2794 (2011)
51. P.B. Gorepatil, Y.D. Mane, V.S. Ingle, Synlett 24, 2241 (2013)
123