P2O5 mediated rapid condensation of 2-aminothiophenol with aromatic aldehydes at ambient temperature

Article abstract of DOI:10.1016/j.cclet.2010.03.006

2-Arylbenzothiazoles formed in good yields (65-90%) by the condensation of aminothiophenols with aromatic aldehydes using P₂O₅ at ambient temperature.

Full text of DOI:10.1016/j.cclet.2010.03.006

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 790–793
www.elsevier.com/locate/cclet
P2O5 mediated rapid condensation of 2-aminothiophenol
with aromatic aldehydes at ambient temperature
b
Santosh V. Nalage a, Sidhanath V. Bhosale a, , Dattatry S. Bhosale ,
*
Wamanrao N. Jadhav b
a Department of Organic Chemistry, North Maharashtra University, Jalgaon 425001, India
b Organic Chemistry Synthesis Laboratory, Dnyanopasak College, Parbhani 431401, India
Received 4 November 2009
Abstract
2-Arylbenzothiazoles formed in good yields (65–90%) by the condensation of aminothiophenols with aromatic aldehydes using
P2O5 at ambient temperature.
# 2010 Sidhanath V. Bhosale. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 2-Arylbenzothiazole; 2-Aminophenol; P2O5
2-Arylbenzothiazoles are synthetically challenging compounds used in the field of drugs and material science. 2-
Arylbenzothiazoles have a ubiquitous presence in pharmaceuticals, such as in antitumor [1], antimicrobial [2] and
antiperkinsonism [3].
2-Arylbenzothiazoles were obtained by a direct cyclocondensation of 2-aminothiophenol with variety of
carboxylic acid in presence of polyphosphoric acid [4] or P2O5-MeSO3H [5]. This method involves long reaction times
ranging 4–10 h under heating condition, which require tedious work-up. Classically 2-arylbenzothiazoles are prepared
from aminothiophenols by cyclocondensation with aromatic aldehydes by various methods. Recently acid catalyst
such as 4-methoxy-TEMPO/O2 [6], H2O2/CeNH4 (NO3)4 [7], TCCA [8], alum [9], polymer supported hypervalent
iodine [10], CAN [11], iodine [12] are used for this transformation.
Although there are many publications on the synthesis of 2-arylbenzothiazole derivatives under microwave
irradiation by using p-TsOH [13], [pmIm]Br [14], K2CO3/BmimPF6 or BmimBF4 [15], Lawesson’s reagent [16],
PTSA [17], Mn(OAc)3 [18], MnO2/SiO2 [19], Montmorillonite K10 [20], there is still a need for a simple and mild
process for preparation of 2-arylbenzothiazole. They are also accessible by a variety of methods including
intramolecular cyclisation of the aryl radical [21], by flash vacuum pyrolyses and photolysis of 2-methylthio-N-
(arenylidene)anilines [22], hypervalent iodine mediated intramolecular cyclisation [23], ligand-accelerated copper
catalyzed cyclisation of ortho-halobenzanilides [24], Pd-catalyzed thiol cross-coupling [25].
* Corresponding author.
E-mail address: sidhanath2003@yahoo.co.in (S.V. Bhosale).
1001-8417/$ – see front matter # 2010 Sidhanath V. Bhosale. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.03.006

S.V. Nalage et al. / Chinese Chemical Letters 21 (2010) 790–793
791
Table 1
P2O5 mediated rapid condensation of 2-aminothiophenol with aromatic aldehydes.
Entry
1
Aldehydea
Productb
Reaction time (yield %)c
3.2 h (89)
3a
2
3
3b
3c
4.2 h (83)
5.0 h (69)
4
5
3d
3e
4.0 h (78)
5.0 h (79)
6
3f
6.0 h (71)
7
8
3g
3h
7.0 h (78)
4.0 h (75)
9
3i
3j
4.0 h (79)
4.0 h (85)
10
11
3k
4.0 h (81)
12
13
3l
5.0 h (66)
5.0 h (70)
3m
a
Reaction conditions: aminothiophenol (1 mmol), aldehyde (1 mmol), P2O5 (10 mol%), stirred for 3–7 h at r.t. Recrystallized using methanol at
cold conditions.
b
All compounds were characterized by using IR, NMR and MS and mp.
c
Isolated yield.

792
S.V. Nalage et al. / Chinese Chemical Letters 21 (2010) 790–793
Scheme 1.
Herein we report an efficient, short reaction time, easy isolation and good yielding protocol for the synthesis of 2-
arylbenzothiazole using P2O5. Several aldehydes were reacted with aminothiophenols under stirring in the presence of
10 mol% P2O5 in methanol as solvent to afforded high yields of 2-arylbenzothiazole. The result (summarized in
Table 1) clearly shows the scope of the method with respect to various substituted aldehydes.
The reaction involving P2O5 have been the subject of current interest because of their great synthetic potential in
organic synthesis, e.g. in the selective deprotection of 1,1 diacetals [26], synthesis of 1,4-DHP [27], synthesis of e-
caprolactam [28], chemoselective synthesis of 1,1-diacetals [29]. Phosphorous pentoxide is an inexpensive reagent,
acts as an acid catalyst. We have observed P2O5 increases the acidic condition of the reaction mixtures which leads to
shorter reaction time. Also, phosphorous pentoxide being soluble in water is easily removed. However, excess addition
of phosphorous pentoxide does not increase the yield of products (Scheme 1).
1. Experimental
Melting points are uncorrected and compare with reported value. IR spectra were recorded on PerkinElmer 1710
spectrometer. 1H NMR spectra were recorded on Varian 200 MHz. The spectra were recorded in DMSO-d6 using TMS
as the internal standard. Mass measurements were carried out on a Thermo Finnigan (Model-LCQ Advantage MAX)
mass spectrometer.
2. Result and discussion
The present study overcomes the drawbacks of previous methods, i.e. conventional heating, longer reaction times,
and expensive catalyst required for the condensation of aldehydes with aminothiophenols. These conditions are
improved at ambient temperature or using microwave irradiation which is becoming an alternative source. In a typical
experimental procedure, the 1 equiv. of aldehyde, 1 equiv. of 2-aminothiophenol, and 10 mol% P2O5 were mixed
thoroughly in methanol as solvent (7–8 mL) and stirred for 3–7 h at room temperature. The reaction was monitored by
TLC. After completion of the reaction, water work-up followed by extraction with suitable solvent afforded clean
product. 2-Arylbenzothiazoles were obtained with good yields (65–90%). Invariably the products obtained were
purified with more ease.
To evaluate the scope of this reaction a variety of aldehydes with different substituent patterns were subjected to the
reactionconditions[30]. TheresultsarepresentedinTable 1. Asisobviousfromthetablethereactionsareingeneralclean,
giving good yields of the products and no side products have been isolated. Electron donating and electron withdrawing
groups on the aromatic ring facilitate the cyclisation process. It is worth mentioning that products were extremely stable
under the reaction conditions. We could not understand why the yield of substituted aldehydes is less as compare to
benzaldehyde. Furthermore, we employed the present protocol for synthesis of 2-substituted benzothiazoles using
heteroaromatic aldehydes (entries 12 and 13). The results are promising with good yield. The cyclocondensation with
aliphatic aldehydes (Valeraldehyde, Isovaleraldehyde, and Heptanal) were sluggish under the present reaction conditions
and afforded the corresponding 2-substituted benzothiazoles with very low yields. Thus in this report we demonstrate the
scope and limitation of the method in the synthesis of 2-substituted benzothiazoles using P2O5 as a catalyst.
3. Conclusion
In conclusion, the present procedure using P2O5 provides an efficient method to synthesize 2-arylbenzothiazoles.
The method offers several advantages like inexpensive catalyst, short reaction times, cleaner reactions and good yields
of products. We believe this will present a better and more practical alternative to the existing methodologies and will
find useful application in organic synthesis.

S.V. Nalage et al. / Chinese Chemical Letters 21 (2010) 790–793
793
Acknowledgments
We are thankful for the financial support from Department of Science and Technology, New Delhi under Fast Track
Young Scientist programme (No. SR/FTP/CS-82/2007).
References
´ ´
[1] (a) V. Beneteau, T. Besson, J. Guillard, et al. Eur. J. Med. Chem. 34 (1999) 1053;
(b) I.H. Hall, N.J. Peaty, J.R. Henry, et al. Arch. Pharm. 332 (1999) 115.
[2] P.J. Palmer, R.B. Trigg, J.V. Warrington, J. Med. Chem. 14 (1971) 248.
[3] P. Jimonet, F. Audiau, M. Barreau, et al. J. Med. Chem. 42 (1999) 2828.
[4] D.W. Hein, R.J. Alheim, J.J. Leavitt, J. Am. Chem. Soc. 79 (2) (1957) 427.
[5] D.L. Boger, J. Org. Chem. 43 (11) (1978) 2296.
[6] Y.X. Chen, L.F. Qian, W. Zhang, et al. Angew. Chem. Int. Ed. 47 (48) (2008) 9330.
[7] K. Bahrami, M.M. Khodaei, F. Naal, J. Org. Chem. 73 (17) (2008) 6835.
[8] H.L. Xiao, J.X. Chen, M.C. Liu, et al. Chem. Lett. 38 (2) (2009) 170.
[9] S.S. Pawar, D.V. Dhekane, M.S. Shingare, et al. Aust. J. Chem. 61 (2008) 905.
[10] A. Kumar, R.A. Maurya, P. Ahmad, J. Comb. Chem. 11 (2009) 198.
[11] F. Al-Qalaf, R.A. Mekheimer, K.U. Sadek, Molecules 13 (2008) 2908.
[12] Y. Li, Y.L. Wang, J.Y. Wang, Chem. Lett. 35 (4) (2006) 460.
[13] S. Paul, M. Gupta, R. Gupta, Synth. Commun. 32 (23) (2002) 3541.
[14] B.C. Ranu, R. Jana, S.S. Dey, Chem. Lett. 33 (3) (2004) 274.
[15] Y. Hu, Z.C. Chen, Z.G. Le, et al. Synth. Commun. 34 (11) (2004) 2039.
[16] J.A. Seijas, M.P. Vazquez-Tato, M.R. Carballido-Reboredo, et al. Synlett 2 (2007) 313.
[17] S. Paul, M. Gupta, R. Gupta, Synth. Commun. 32 (2002) 3541.
[18] X.J. Mu, J.P. Zou, R.S. Zeng, et al. Tetrahedron Lett. 46 (2002) 4345.
[19] K. Bougrin, A. Loupy, M. Soufiaoui, Tetrahedron 54 (1998) 8055.
[20] A. Ben-Alloum, S. Bakkas, M. Soufiaoui, Tetrahedron Lett. 38 (36) (1997) 6395.
[21] N.K. Downer-Riley, Y.A. Jackson, Tetrahedron 64 (33) (2008) 7741.
[22] C.H. Chou, P.C. Yu, B.C. Wang, Tetrahedron Lett. 49 (26) (2008) 4145.
[23] D.S. Bose, M. Idrees, J. Org. Chem. 71 (21) (2006) 8261.
[24] G. Evinder, R.A. Batey, J. Org. Chem. 71 (5) (2006) 1802.
[25] R.J. Perry, B.D. Wilson, Organometallics 13 (1994) 3346.
[26] H. Eshghi, P. Shafieyoon, J. Chin. Chem. Soc. 52 (1) (2005) 155.
[27] M.B. Deshmukh, P.V. Anbhule, S.D. Jadhav, et al. Indian J. Chem. 46B (2007) 1545.
[28] R.X. Ren, L.D. Zueva, W. Ou, Tetrahedron Lett. 42 (48) (2001) 8441.
[29] A.R. Hajipour, A. Zarei, A.E. Ruoho, Tetrahedron Lett. 48 (16) (2007) 2881.
[30] General method: A mixture of aldehyde (1 mmol), 2-aminothiophenol (1 mmol), and P2O5 (10 mol%) in methanol (7–8 mL) act as the solvent.
Stirr the mixtures for 3–7 h. On completion of reaction solvent was removed invacuo. Then crude mixture was diluted with EtOAc (30 mL) and
washed with H2O (2 ꢀ 30 mL). The organic layer was dried over MgSO4, and removed the solvent in vacuo. The separated solid was then
recrystallized using methanol and placed in freezer. The pure product was crystallized on cooling, and then filtered. Spectral data for the
selected compounds: 2-phenylbenzothiazole (3a): 1H NMR (200 MHz, DMSO-d6): d 8.05–8.00 (d, 2H), 7.98–7.92 (m, 2H), 7.49–7.46 (d, 2H),
7.30–7.40 (m, 3H); IR (neat, cmꢁ1) 3064, 3025, 1606, 1580, 1313, 1028; MS (m/z): 211.18 (M+); mp: 114 8C. 2-4(-Methoxyphenyl)ben-
zothiazole (3b): 1H NMR (200 MHz, DMSO-d6): d 7.99–7.95 (d, 2H), 7.92(d, 1H), 7.88 (d, 1H), 7.44 (t, 1H), 7.32 (t, 1H), 7.01 (d, 1H), 6.97 (d,
1H), 3.84 (s, 3H, OMe); IR (neat, cmꢁ1) 3105, 3060, 1606, 1310, 1576, 1120; MS (m/z): 241 (M+); mp: 120 8C. 2-(30-Nitrophenyl)ben-
zothiazole (3c): 1H NMR (200 MHz, DMSO-d6): d 8.90 (s, 1H), 8.47 (d, 1H), 8.42 (d, 1H), 8.49 (d, 1H), 8.42 (d, 1H), 7.86 (t, 1H), 7.59 (t, 1H),
7.50 (t, 1H); IR (neat, cmꢁ1) 3065, 1635, 1560, 1290; MS (m/z) 256.20(M+), 257.11 (M+1); mp: 180 8C. 2-(30,40-Dimethoxyphenyl)ben-
zothiazole (3i): 1H NMR (200 MHz, DMSO-d6): (8.14 (d, 1H), 8.03 (d, 1H), 7.85 (s, 1H), 7.71 (d, 1H), 7.63 (t, 1H), 7.53 (t, 1H), 7.12 (d, 1H),
4.16 (s, 3H, OMe), 4.09 (s, 3H, OMe)); IR (neat, cmꢁ1) 3105, 1598, 1311, 1145, 1017, 870; MS (m/z): 271.26 (M+); mp: 132 8C. 2-(30,40,50-
Trimethoxyphenyl)benzothiazole (3j): 1H NMR (200 MHz, DMSO-d6): d 8.08 (d, 1H), 7.98 (d, 1H) 7.57 (t, 1H), 7.50 (t, 1H), 7.39 (s, 2H), 4.05
(s, 3H, OMe), 3.99 (s, 3H, OMe), 3.94 (s, 3H, OMe); 3100, 3030, 1582, 1125, 989, 887; MS (m/z): 301.2 (M+); mp: 152 8C.