Phenyliodine(III) bis(trifluoroacetate) mediated synthesis of 2-aryl-1,2-benzisothiazol-3(2H)-ones in ionic liquid

Article abstract of DOI:10.1002/jccs.200700021

Treatment of N-aryl-2-(benzylthio)benzamides with phenyliodine(III) bis(trifluoroacetate) containing trifluoroacetic acid resulted in an interrupted Pummerer-type reaction in ionic liquid 1-n-butyl-3-methylimidazolium hexafluorophosphate, [bmim][PF_6<

Full text of DOI:10.1002/jccs.200700021

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Journal of the Chinese Chemical Society, 2007, 54, 127-130
127
Phenyliodine(III) bis(trifluoroacetate) Mediated Synthesis of
2-Aryl-1,2-benzisothiazol-3(2H)-ones in Ionic Liquid
Huey-Min Wanga (
Hsin-Yu Huangc (
aChung Hwa College of Medical Technology, Tainan 717, Taiwan, R.O.C.
), I-Chian Liangb (
), Rei-Sheu Houa (
),
) and Ling-Ching Chenc* (
)
bDepartment of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
cGraduate Institute of Pharmaceutical Sciences, College of Pharmacy, Kaohsiung Medical University,
Kaohsiung 807, Taiwan, R.O.C.
Treatment of N-aryl-2-(benzylthio)benzamides with phenyliodine(III) bis(trifluoroacetate) contain-
ing trifluoroacetic acid resulted in an interrupted Pummerer-type reaction in ionic liquid 1-n-butyl-3-
methylimidazolium hexafluorophosphate, [bmim][PF6] to give 2-aryl-1,2-benzisothiazol-3(2H)-ones
rather than the normal Pummerer-type products.
Key words: Ionic liquid; Phenyliodine(III) bis(trifluoroacetate); Interrupted Pummerer-type reac-
tion.
INTRODUCTION
Room temperature ionic liquids (RTIL) are liquids
(PIFA).17 We report here an interrupted Pummerer-type re-
action of sulfides using PIFA, which has been applied to
prepare 2-aryl-1,2-benzisothiazole-3(2H)-ones in ionic
liquid via intramolecular N-S bond formation.
that are composed entirely of ions. In fact, ionic liquids can
now be produced which remain liquid at room temperature
and below (even as low as -90 °C) and appear to be unde-
manding and inexpensive to manufacture.1 Ionic liquids of-
fer an attractive alternative to conventional organic liquids
for clean synthesis, as they are easy to recycle, lack flam-
mability, and possess effectively no vapour pressure. Com-
pared with classical molecular solvents, the ionic liquids
are environmentally benign reaction media.2 To date some
of the more important reactions have been carried out and
investigated in ionic liquids, for example, Friedel-Crafts
reaction,3 alkoxycarbonylation,4 hydrogenation,5 Diels-
Alder reaction,6 Wittig reaction,7 Heck reaction,8 Trost-
Tsuji coupling,9 Ring-closing metathesis (RCM),10 Suzuki
cross-coupling,11 Fischer indole synthesis,12 1,3-dipolar
cycloaddition reaction,13 Beckmann rearrangement,14 the
Knoevenagel and Robinson annulation reactions,15 etc.
Recently, hypervalent iodine reagents have been used
extensively in organic synthesis due to their low toxicity,
ready availability and easy handling. As a continuation of
our studies concerning hypervalent iodine(III) chemistry,16
we have reported a Pummerer-type reaction that provides a
very simple and convenient procedure for the preparation
of 4H-pyrrolo[2,1-c][1,4]benzothiazines by treatment of
a-acyl sulfides with phenyliodine(III) bis(trifluoroacetate)
RESULTS AND DISCUSSION
The requisite N-aryl-2-(benzylthio)benzamides (2)
were readily prepared from 2-(benzylthio)benzoic acid (1)
with NCS/Ph3P-complex followed by treatment with ap-
propriate arylamines.18 Treatment of 2 with PIFA contain-
ing trifluoroacetic acid (TFA) in ionic liquid 1-n-butyl-3-
methylimidazolium hexafluorophosphate, [bmim][PF6] at
room temperature caused cyclization to give 2-aryl-1,2-
benzisothiazol-3(2H)-ones (3) in moderate to good yields.
Apparently, without the electron withdrawing group on the
carbon alpha to the sulfide group, trifluoroacetate ion is not
basic enough to generate the thionium ion. Under these
conditions no sulfoxides or normal Pummerer-type prod-
ucts were obtained (Scheme I).
The scope of the reaction of various N-aryl-2-(ben-
zylthio)benzamides (2) with PIFA containing TFA oc-
curred easily in ionic liquid [bmim][PF6] at room tempera-
ture for 2 h to give the desired 2-aryl-1,2-benzisothiazol-
3(2H)-ones (3). The results are given in Table 1. It was ob-
served that electron-rich aromatic substituents on the nitro-
gen led to improved yields of cyclization with sulfides

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128 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Wang et al.
Scheme I
Table 1. Yields of 2-aryl-1,2-benzisothiol-3-(2H)-ones (3) in
the reaction of sulfides 2 with PIFA in ionic liquid
[bmim][PF6]
Run substrate
R
product Yield/%
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
Ph
3a
3b
3c
3d
3e
3f
78
76
84
83
76
80
70
62
60
CH2Ph
4-MeC6H4
4-MeOC6H4
3,5-(MeO)2C6H3
3,4,5-(MeO)3C6H2
4-ClC6H4
2g
2h
2i
3g
3h
3i
4-EtO2CC6H4
4-NCC6H4
(2c-f) (Table 1, Runs 3~6). When the reaction was con-
ducted in the conventional solvents, such as dichloro-
methane, the preparation of 2-phenyl-1,2-benzisothiazol-
3(2H)-one (3a) needs refluxing for 3 h.19
8.13 (m, 4H). 13C NMR (CDCl3, 100 MHz) d: 120.0, 120.0,
124.5, 125.1, 127.3, 128.1, 128.8, 129.3, 129.7, 132.3,
134.5, 139.8, 164.4. MS (EI) m/z: 227 (M+), 198, 195, 167,
108, 69.
In summary, our results herein demonstrate that the
use of a combined reagent PIFA-TFA in ionic liquid [bmim]
[PF6] can be performed rapidly for the interrupted Pummerer-
type reaction of sulfides to prepare 2-aryl-1,2-benzisothi-
azol-3(2H)-ones at room temperature under mild condi-
tions. The ionic liquid plays the dual role of solvent and
promoter. Separation of products from the ionic liquids is
very straightforward, as is recycling of the ionic liquid.
2-Benzyl-1,2-benzisothiazol-3(2H)-one (3b)
mp 88-89 °C (AcOEt-hexane) (lit.,20 87.5-88.5 °C).
IR (KBr) n: 1650 cm-1. 1H NMR (CDCl3) d: 5.06 (s, 2H),
7.30-7.37 (m, 5H), 7.38-8.08 (m, 4H). 13C NMR (CDCl3,
100 MHz) d: 47.5, 120.3, 124.4, 125.5, 126.7, 128.2, 128.4,
128.6, 128.8, 131.8, 131.8, 136.1, 140.4, 165.3. MS (EI)
m/z: 241 (M+), 136, 92, 91, 65.
EXPERIMENTAL SECTION
2-(4-Methylphenyl)-1,2-benzisothiazol-3(2H)-one (3c)
mp 135-136 °C (CHCl3-hexane) (lit.,20 135-137 °C).
IR (KBr) n: 1644 cm-1. 1H NMR (CDCl3) d: 2.39 (s, 3H),
7.28-7.59 (m, 4H), 7.63-8.11 (m, 4H). 13C NMR (CDCl3,
100 MHz) d: 21.1, 120.0, 120.0, 125.7, 127.4, 129.9, 129.9,
129.9, 130.4, 132.2, 133.3, 134.5, 137.2, 164.1. MS (EI)
m/z: 241 (M+), 226, 208, 198, 180.
All melting points are uncorrected. The IR spectra
were recorded on a Shimadzu IR-27 G spectrophotometer.
1H NMR and 13C NMR spectra were recorded on a Varian
Unity Plus 400 MHz. Chemical shifts (d) were measured in
ppm with respect to TMS. MS were obtained on a JEOL
JMS D-300 instrument.
Typical procedure for the preparation of 2-phenyl-
1,2-benzisothiazol-3(2H)-one (3a)
2-(4-Methoxyphenyl)-1,2-benzisothiazol-3(2H)-one (3d)
mp 145-146 °C (CHCl3-hexane) (lit.,20 147-148 °C).
IR (KBr) n: 1664 cm-1. 1H NMR (CDCl3) d: 3.84 (s, 3H),
6.96-7.57 (m, 4H), 7.59-8.11 (m, 4H). 13C NMR (CDCl3,
100 MHz) d: 55.6, 114.6, 114.6, 120.1, 120.1, 125.2, 127.1,
129.3, 129.7, 132.2, 133.4, 134.5, 158.8, 164.3. MS (EI)
m/z: 257 (M+), 242, 209, 136, 121, 106.
A solution of N-aryl-2-(benzylthio)benzoic acid (2a)
(160 mg, 0.5 mmol) in [bmim][PF6] (2 mL) was treated
with PIFA (258 mg, 0.6 mmol) containing TFA (114 mg, 1
mmol) and the mixture was stirred at room temperature for
2 h. Subsequently, the reaction mixture was extracted with
Et2O. The remaining ionic liquid was reused after drying in
a vacuum. The extract was concentrated under reduced
pressure and the residue was chromatographed on silica gel
eluting with CHCl3-hexane (3:1) to give 3a. mp 142-143.5
°C (AcOEt-hexane) (lit.,26 140.5-141.5 °C). IR (KBr) n:
1662 cm-1. 1H NMR (CDCl3) d: 7.28-7.56 (m, 5H), 7.43-
2-(3,5-Dimethoxyphenyl)-1,2-benzisothiazol-3(2H)-one
(3e)
mp 103-104 °C (AcOEt-hexane) (lit.,20 103-104 °C).
IR (KBr) n: 1679 cm-1. 1H NMR (CDCl3) d: 3.83 (s, 6H),

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Synthesis of 2-Aryl-1,2-benzisothiazol-3(2H)-ones
J. Chin. Chem. Soc., Vol. 54, No. 1, 2007 129
6.42 (t, J = 2.2 Hz, 1H), 6.93 (d, J = 2.2 Hz, 2H), 7.40-8.11
(m, 4H). 13C NMR (CDCl3, 100 MHz) d: 55.6, 55.6, 99.5,
102.7, 102.7, 120.0, 125.0, 125.8, 127.1, 132.41, 138.9,
139.8, 161.1, 161.1, 164.1. MS (EI) m/z: 287 (M+), 258,
151, 136, 108, 69.
work. (Grant No. 94-2113-M-037-008).
Received April 24, 2006.
2-(3,4,5-Trimethoxyphenyl)-1,2-benzisothiazol-3(2H)-
one (3f)
REFERENCES
mp 120-121 °C (AcOEt-hexane) (lit.,20 120-121 °C).
IR (KBr) n: 1666 cm-1. 1H NMR (CDCl3) d: 3.87 (s, 3H),
3.90 (s, 6H), 6.93 (s, 2H), 7.44-8.11 (m, 4H). 13C NMR
(CDCl3, 100 MHz) d: 56.3, 56.3, 56.3, 102.8, 102.8, 120.0,
124.7, 125.9, 127.1, 132.4, 132.6, 137.2, 139.9, 153.5,
153.5, 164.2. MS (EI) m/z: 317 (M+), 302, 274, 216, 136,
108, 93, 69.
1. (a) Welton, T. Chem. Rev. 1999, 99, 2071. (b) Wasserscheid,
P.; Keim, W. Angew. Chem. Int. Ed. 2000, 39, 3772.
2. (a) Zhang, S.; Zhang, Q.; Zhang, Z. C. Ind. Eng. Chem. Res.
2004, 43, 614. (b) Esser, J.; Wasserscheid, P.; Jess, A. Green
Chem. 2004, 6, 316. (c) Wang, Y.; Li, H. R.; Wang, C. M.;
Hui, J. Chem. Commun. 2004, 1938. (d) Gmouh, S.; Yang,
H.; Vaultier, M. Org. Lett. 2003, 5, 3365.
3. (a) Surette, J. K. D.; Green, L.; Singer, R. D. Chem.
Commun. 1996, 2753. (b) Boon, J. A.; Levisky, J. A.; Pflug,
J. L.; Wilkes, J. S. J. Org. Chem. 1986, 51, 480. (c) Adams,
C. J.; Earle, M. J.; Roberts, G.; Seddon, K. R. Chem.
Commun. 1998, 2097. (d) Stark, A.; MacLean, B. L.; Singer,
R. D. J. Chem. Soc. Dalton Trans. 1999, 63.
2-(4-Chlorophenyl)-1,2-benzisothiazol-3(2H)-one (3g)
mp 127-128 °C (CHCl3-hexane) (lit.,20 128-129 °C).
IR (KBr) n: 1654 cm-1. 1H NMR (CDCl3) d: 7.42-7.68 (m,
4H), 7.60-8.11 (m, 4H). 13C NMR (CDCl3, 100 MHz) d:
120.1, 120.1, 125.5, 127.1, 128.4, 129.4, 129.4, 129.8, 132.4,
132.5, 134.7, 139.5, 164.0. MS (EI) m/z: 263 (M++2), 261
(M+), 226, 198, 108, 69.
4. Zim, D.; de Souza, R. F.; Dupont, J.; Monteiro, A. L. Tetra-
hedron Lett. 1998, 39, 7071.
5. (a) Dyson, P. J.; Ellis, D. J.; Parker, D. G.; Welton, T. Chem.
Commun. 1999, 25. (b) Monteiro, A. L.; Zinn, F. K.; de
Souza, R. F.; Dupont, J. Tetrahedron: Asymmetry 1997, 8,
177. (c) Fisher, T.; Sethi, A.; Welton, T.; Woolf, J. Tetrahe-
dron Lett.1999, 40, 793. (d) Adams, C. J.; Earle, M. J.; Sed-
don, K. R. Chem. Commun. 1999, 1043. (e) Einloft, J. E. L.;
de Souza, R. F.; Dupont, J. Polyhedron 1996, 15, 1217.
6. (a) Howarth, J.; Hanlon, K.; Fayne, D.; McCormac, P. Tetra-
hedron Lett. 1997, 38, 3097. (b) Earle, M.; McCormac, P. B.;
Seddon, R. K. Green Chem. 1999, 1, 23. (c) Huddleston, J.
G.; Willauer, H. D.; Swatloski, R. P.; Visser, A. E.; Rogers,
R. D. Chem. Commun. 1998, 1765. (d) Song, C. E.; Shim, W.
H.; Roh, E. J.; Lee, S.; Choi, J. H. Chem. Commun. 2001,
1122.
2-[(4-Ethoxycarbonyl)phenyl]-1,2-benzisothiazol-3(2H)-
one (3h)
mp 151-153 °C (CHCl3-hexane) (lit.,20 151-153 °C).
IR (KBr) n: 1702 cm-1, 1667 cm-1. 1H NMR (CDCl3) d: 1.41
(t, J = 7.2 Hz, 3H), 4.39 (q, J = 7.2 Hz, 2H), 7.44-8.12 (m,
4H), 7.87-8.15 (m, 4H). 13C NMR (CDCl3, 100 MHz) d:
14.3, 61.1, 120.1, 122.9, 122.9, 124.8, 126.0, 127.3, 128.2,
130.8, 132.8, 132.8, 139.5, 141.5, 164.2, 165.8. MS (EI)
m/z: 299 (M+), 271, 254, 226, 198, 171, 136, 108, 69.
7. Boulaire, V. L.; Gree, R. Chem. Commun. 2000, 2195.
8. (a) Calo, V.; Nacci, A.; Lopez, L.; Mannarini, N. Tetrahe-
dron Lett. 2000, 41, 8973. (b) Xu, L. J.; Chen, W. P.; Xiao, J.
L. Organometallics 2000, 19, 1123. (c) Carmichael, A. J.;
Earle, M. J.; Holbrey, J. D.; McCormac, P. B.; Seddon, K. R.
Org. Lett. 1999, 1, 997. (d) Deshmukh, R. R.; Rajagopal, R.;
Srinivasan, K. V. Chem. Commun. 2001, 1544. (e) Bohm, V.
P. W.; Herrmann, W. A. Chem. Eur. J. 2000, 6, 1017.
9. de Bellefon, C.; Pollet, E.; Grenouillet, P. J. Mol. Catal.
1999, 145, 121.
2-(4-Cyanophenyl)-1,2-benzisothiazol-3(2H)-one (3i)
mp 184.5-185.5 °C (AcOEt-hexane) (lit.,20 184.5-
185.5 °C). IR (KBr) n: 2222, 1653 cm-1. 1H NMR (CDCl3)
d: 7.46-8.12 (m, 4H), 7.74-7.98 (m, 4H). 13C NMR (CDCl3,
100 MHz) d: 109.5, 111.8, 112.1, 118.3, 120.2, 120.2,
123.3, 124.6, 126.3, 127.5, 133.2, 133.3, 141.6, 164.2. MS
(EI) m/z: 252 (M+), 220, 192, 136, 108, 69.
10. (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413. (b)
Buijsman, R. C.; van Vuuren, E.; Sterrenburg, J. G. Org.
Lett. 2001, 3, 3785.
ACKNOWLEDGEMENT
11. Mathews, C. J.; Smith, P. J.; Welton, T. Chem. Commun.
2000, 1249.
We gratefully acknowledge the National Council Sci-
ence of the Republic of China for financial support of this

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
130 J. Chin. Chem. Soc., Vol. 54, No. 1, 2007
Wang et al.
12. Rebeiro, G. L.; Khadilkar, B. M. Synthesis 2001, 370.
13. Dubreuil, J. F.; Bazureau, J. P. Tetrahedron Lett. 2000, 41,
7351.
1990, 365. (h) Varvoglis, A. The Organic Chemistry of
Polycoordinated Iodine; VCH: New York, 1992. (i) Kita, Y.;
Tohma, H.; Yakura, T. Trends Org. Chem. 1992, 3, 113. (j)
Kita, Y.; Tohma, H. Farumashia 1992, 28, 984. (k) Stang, P.
J. Angew. Chem. Int. Ed. Engl. 1992, 31. 274. (l) Kitamura,
T. Yuki Gosei Kagaku Kyokaishi 1995, 53, 893. (m) Stang, P.
J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123. (n) Kitamura,
T.; Fujiwara, Y. Org. Prep. Proc. Int. 1997, 29, 411.
17. Wang, H.-M.; Lin, M.-C.; Chen, L.-C. Heterocycles 1994,
38, 1519.
14. (a) Izumi, Y.; Sato, S.; Urabe, K. Chem. Lett. 1983, 1649. (b)
Peng, J.; Deng, Y. Tetrahedron Lett. 2001, 42, 403.
15. Morrison, D. W.; Forbes, D. C.; James, H. Tetrahedron Lett.
2001, 42, 6053.
16. Reviews see: (a) Banks, D. F. Chem. Rev. 1996, 66, 243. (b)
Varvoglis, A. Chem. Soc. Rev. 1981, 10, 377. (c) Koser, G. F.
In The Chemistry of Functional Groups, Supplement D;
Patai, S.; Rappoport, Z., Ed.; Wiley: New York, 1983, Ch. 18
and 25. (d) Varvoglis, A. Synthesis 1984, 709. (e) Moriaty,
R. M.; Prakash, O. Acc. Chem. Res. 1986, 19, 244. (f)
Ochiai, M.; Nagao, Y. Yuki Gosei Kagaku Kyokaishi 1986,
44, 660. (g) Moriarty, R. M.; Vaid, R. K.; Koser, G. F. Synlett
18. Froyen, P. Synth. Commun. 1995, 25, 959.
19. Wang, H.-M.; Huang, H.-Y.; Kang, I.-J.; Chen, L.-C.
Hetrocycles 2001, 55, 1231-1235.
20. Uchida, Y.; Kozuka, S. Bull. Chem. Soc. Jpn. 1982, 55, 1183.