An efficient copper mediated synthetic methodology for benzo[d]isothiazol- 3(2H)-ones and related sulfur-nitrogen heterocycles

Article abstract of DOI:10.1016/j.tetlet.2012.01.003

A copper mediated sulfur-nitrogen coupling reaction for the synthesis of benzo[d]isothiazol-3(2H)-ones and related sulfur-nitrogen heterocycles has been presented, which requires 2-halo-arylamides, sulfur powder, 25-50 mol % of copper iodide/1,10-phenanthroline, and potassium carbonate as base.

Full text of DOI:10.1016/j.tetlet.2012.01.003

Tetrahedron Letters 53 (2012) 1354–1357
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An efficient copper mediated synthetic methodology for
benzo[d]isothiazol-3(2H)-ones and related sulfur–nitrogen heterocycles
⇑
Bhagat Singh Bhakuni, Shah Jaimin Balkrishna, Amit Kumar, Sangit Kumar
Department of Chemistry, Indian Institute of Science Education and Research Bhopal (IISER), MP 462 023, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A copper mediated sulfur–nitrogen coupling reaction for the synthesis of benzo[d]isothiazol-3(2H)-ones
and related sulfur–nitrogen heterocycles has been presented, which requires 2-halo-arylamides, sulfur
powder, 25–50 mol % of copper iodide/1,10-phenanthroline, and potassium carbonate as base.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 3 November 2011
Revised 3 January 2012
Accepted 4 January 2012
Available online 10 January 2012
Keywords:
Copper catalysis
Benzo[d]isothiazol-3(2H)-ones
Carbon–sulfur bond formation
Sulfur
Transition metal catalyzed carbon hetero-atom coupling reac-
tions have emerged as a new method to synthesize a diverse series
of hetero-atom (S, Se, and Te) containing organic molecules.1,2
Among these, copper catalyzed synthesis of unsymmetrical diaryl
sulfides, diaryl disulfides, arylthiols, arylsulfinamides, benzothiaz-
oles, and copper catalyzed 1,2-hydroxysulfenylation of alkenes
have been well explored.2–4 It is of interest to note that the cata-
lytic methods to synthesize sulfur–nitrogen heterocycles (ben-
zoisothiazolones) have not been reported till date.
Organosulfur–nitrogen heterocycles are well known for their
biological activity, ability to eject Zn2+ ion from certain proteins
and redox regulation of tyrosine protein phosphatase.4,5 Ben-
zoisothiazolone derivatives have been studied for their synthetic
utility in carbon–carbon bond forming reactions.6 In view of their
potential applications, several methods have been developed to
synthesize S–N heterocycles.7,8,6b,9–15 The reported methods on
benzoisothiazolones are depicted in Scheme 1.
In the classical method, 2-mercaptobenzoic acid was converted
into 2-sulfenylchloro-benzoylchloride by the treatment of thionyl
chloride and chlorine gas. Thereafter, quenching with primary
amines gives respective benzoisothiazolones (Eq. 1).7 Alternative
route for the synthesis of S–N has been developed by employing
environmentally benign hyper-valent iodine reagent [phenyl
iodine (III)-bistrifluoroacetate] on 2-mercapto-N-aryl/alkylbenza-
mide substrates (Eq. 2).8 Conversion of 2-(t-butylthio)-5-nitro-
benzamide into S–N heterocycle has been reported by the
treatment of trimethylsilyl chloride (Eq. 3).6b,9 The introduction
of t-butylthiol into the aromatic ring is the key step in this trans-
formation and seems to be facile only for activated 2-chloro-5-ni-
tro-arylamide substrate. Wright et al. has reported t-butyl
sulfoxide and benzylbutyl sulfoxide as sulfenyl halide equivalent
for ring closing S–N bond formation reaction (Eq. 4).10
From our literature survey on benzoisothiazolones, it seems
that the synthesis of S–N heterocycles mainly relies on 2-merca-
ptobenzoic acid.7,8,11–14 Although, 2-mercaptobenzoic acid is com-
mercially available, conversion of this into S–N heterocycle
involves multi-steps (Eq. 2) and/or use of highly toxic and corro-
sive reagents. Furthermore, synthesis of substituted aromatic S–N
heterocycles has not been well documented presumably due to
poor availability of substituted 2-mercaptobenzoic acid. Therefore,
it would be desirable to explore a practical and environmentally
benign method by which a diverse library of aryl benzoisothiazol-
ones could be accessed from readily available substrates.
Our group has recently developed a copper catalyzed Se–N cou-
pling reaction for the synthesis of organoselenium–nitrogen het-
erocycles.16 Here in this study, for the first time, we report the
application of this copper catalyzed reaction for the synthesis of
sulfur-nitrogen heterocycles from readily accessible 2-halo-aryla-
mide substrates and sulfur powder (Eq. 5).
We began our studies on 2-iodo-, 2-bromo-, 2-chloro-N-ben-
zylbenzamides to utilize chloro, bromo, iodo substrates in the cop-
per catalyzed S–N coupling reaction. It was noticed that iodo,
bromo, and chloro substrates reacted smoothly with sulfur powder
in the presence of potassium carbonate as base by employing 25,
30, and 50 mol % of copper iodide/1,10-phenanthroline catalyst,17
respectively, at 110 °C in DMF (Table 1, entry 1). As expected iodo
and bromo substrates gave 1 in 89 and 69% yields, respectively.
⇑
Corresponding author.
E-mail address: Sangitkumar@iiserbhopal.ac.in (S. Kumar).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.01.003

B. S. Bhakuni et al. / Tetrahedron Letters 53 (2012) 1354–1357
1355
OH
Cl
O
O
O
i) SOCl2
ii) Cl2
R-NH2
N
R
(1)
(2)
(3)
S
S)2
O
SCl
O
O
AlMe3
R-NH2
PhI(OCOCF3)2
CF3CO2H
NHR
SH
OMe
N
R
S
R
SH
O
O
O
O2N
O2N
O2N
NHR
NHR
tBu-SH
Me3SiCl
DMSO
N
Cl
S-tBu
S
O
O
R1
R2
R1
R2
NHR
Ph
(Cl3CCO)2O
N
R
(4)
S
S
O
Scheme 1. Reported reaction path for the synthesis of sulfur–nitrogen heterocycles.
Table 1
Table 1 (continued)
Synthesis of benzo[d]isohiazol-3(2H)-ones by CuI/L coupling reaction
Entry Producta (yield %)
Entry Producta (yield %)
O
R
13
14
13 4-Cl (85)
14 4-Br (80)
O
N
CuI/ligand
(5)
O
O
N R
H
S powder, K2CO3
DMF, 110ºC
X
S
X = Cl, Br, I
R = Aryl, Alkyl etc
N
S
R
N-R
S
15
16
15 R, –(CH2)2OH (90)d
16 R, –(CH2)3OH (70)d
29
29 R, Benzyl (91)
Entry Producta (yield %)
Entry Producta (yield %)
a
Isolated yield and product was obtained from 2-iodo-arylamide, 1.2 equiv of S
O
O
powder, 25 mol % of CuI/1,10-phenanthroline (L) in the presence of 1.2 equiv K2CO3,
otherwise noted.
N-R
S
N
R
b
Product was obtained from 2-bromo-aryl amide substrates.
Product was obtained from 2-chloro-aryl amide.
30 mol % of CuI/L was used.
50 mol % of CuI/L was used.
S
c
d
O
e
f
RHN
100 mol % CuI/L was used. For more information on reagents and reaction
1
2
1 R, Benzyl (89), (69),b (47)c 17
2 R, Ph (84)
17 R, Ph (88)b,d
conditions, please see Table 2.
18
18 R, Phenylethyl (89)b,d
O
O
R
However, chloro substrate gave low yield (47%) in the presence of
50 mol % CuI/L. It was observed that reaction did not go to comple-
tion in the presence of 10 mol % of CuI/L for 2-iodo-N-benzylbenza-
mide substrate. Furthermore, even prolonged heating from 5 to
24 h did not improve the yield of S–N product. Therefore, high cat-
alyst loading (25–50 mol %) seems to be crucial for the complete
conversion of substrates. Copper iodide and 1,10-phenanthroline
are indispensable, as the reaction does not occur with only copper
iodide or ligand alone.
By employing 25–50 mol % of CuI/L complex, a series of S–N
heterocycles 1–29 were synthesized and isolated in 42–95% yield
(Table 1).18,19 The synthesis of benzoisothiazolone 1, which is a
multi-step reaction, has been reported by many researchers.6b,9,8,12a
In our CuI/L reaction system, benzoisothiazolone 1 was obtained in
single pot from readily accessible 2-chloro-, 2-bromo-, and 2-iodo-
benzylbenzamides in 47–89% yield. Similarly, N-phenylisothiazo-
lone 2 was obtained from respective iodo substrate in an 84% yield.
A small amount (ꢀ5%) of respective diaryl monosulfide was also
observed in the reaction mixture of 2. However, formation of
N
R
N
S
S
3
4
5
6
7
3 R, Me (80)
4 R, Butyl (82)
5 R, Phenylethyl (88)
6 R, Cyclohexyl (90)
7 R, Allyl (91)
19
20
21
22
23
19 R, 3-CO2Et (71)
20 R, 4-CO2Et (72)
21 R, 2-OMe (90)
22 R, 4-OMe (91)
23 R, 3,5-di-OMe (85)
O
4
O
5
R
R
N
R1
N
R1
S
S
6
7
8
9
10
8 R1,7-NO2, R, Benzyl (65)c
24
24 R1, 7-OMe, R, Ph (62)c,e
9 R1, 5-NO2, R, Benzyl (92)c 25
25 R1, 5-OMe, R, Benzyl (61)b,e
26 R1, 7-Me, R, Benzyl (91)
10 R1, 5-NO2, R, Allyl (95)c
26
O
O
X
N-R
N
S
11 4-F (94)
12 3-F (90)
S
N
11
12
27
28
27 R, Cyclohexyl (60)c,f
28 R, Benzyl (40)c,f

1356
B. S. Bhakuni et al. / Tetrahedron Letters 53 (2012) 1354–1357
O
CuIL
O
NHR
X
N
R
S
K2CO3 + S
O
O
NR
S
excess base
NR
SCuL
CuL
Cl
2
X
A
B
Scheme 2. Proposed mechanism for copper mediated synthesis of S–N heterocycles.
Table 2
Amounts of substrates and reagents used for the synthesis of respective arylisothiazolones
Entry
Substrate mg (mmol)
Sulfur mg (mmol)
CuI mg (mmol)
Ligand mg (mmol)
K2CO3 mg (mmol)
Time (h)
Product, yield (mg)
1a
1b
1c
2
3
4
5
6
7
8
Ar-I, 674 (2.0)
Ar-Br, 290 (1.0)
Ar-Cl, 246 (1.0)
Ar-I, 646 (2.0)
Ar-I, 154 (0.6)
Ar-I, 240 (0.8)
Ar-I, 180 (0.5)
Ar-I, 362 (1.1)
Ar-I, 145 (0.5)
Ar-Cl, 320 (1.1)
Ar-Cl, 430 (1.5)
Ar-Cl, 100 (0.4)
Ar-I, 515 (1.5)
Ar-I, 680 (2.0)
Ar-I, 350 (1.0)
Ar-I, 240 (0.6)
Ar-I, 171 (0.6)
Ar-I, 361 (1.2)
Ar-Br, 500 (1.3)
Ar-Br, 316 (0.7)
Ar-I, 395 (1.0)
Ar-I, 310 (0.8)
Ar-I, 275 (0.8)
Ar-I, 430 (1.2)
Ar-I, 380 (1.0)
Ar-Cl, 370 (1.4)
Ar-Br, 250 (0.8)
Ar-I, 430 (1.2)
Ar-Cl, 365 (1.5)
Ar-Cl, 300 (1.2)
Ar-I, 200 (0.5)
80 (2.4)
41 (1.3)
43 (1.3)
80 (2.5)
23 (0.7)
30 (0.9)
20 (0.6)
42 (1.3)
19 (0.6)
42 (1.3)
57 (1.8)
16 (0.5)
58 (1.8)
76 (2.4)
37 (1.2)
23 (0.7)
22 (0.7)
45 (1.4)
49 (1.5)
27 (0.8)
38 (1.2)
30 (0.9)
30 (0.9)
47 (1.5)
38 (1.2)
54 (1.6)
30 (0.9)
47 (1.5)
59 (1.8)
47 (1.5)
20 (0.6)
95 (0.5)
57 (0.3)
95 (0.5)
95 (0.5)
28 (0.15)
38 (0.2)
24 (0.1)
52 (0.3)
24 (0.1)
52 (0.3)
70 (0.4)
20 (0.1)
72 (0.4)
95 (0.5)
47 (0.2)
28 (0.15)
33 (0.17)
68 (0.35)
72 (0.4)
40 (0.2)
48 (0.25)
37 (0.2)
37 (0.2)
58 (0.3)
47(0.25)
134 (0.7)
74 (0.4)
58 (0.3)
291 (1.5)
232 (1.2)
25 (0.1)
90 (0.5)
54 (0.3)
90 (0.5)
90 (0.5)
27 (0.15)
36 (0.2)
22 (0.1)
49 (0.3)
23 (0.1)
50 (0.3)
67 (0.4)
19 (0.1)
68 (0.4)
90 (0.5)
44 (0.2)
27 (0.15)
32 (0.17)
64 (0.35)
68 (0.4)
38 (0.2)
45 (0.25)
35 (0.2)
35 (0.2)
55 (0.3)
45 (0.25)
128 (0.7)
70 (0.4)
55 (0.3)
276 (1.5)
220 (1.2)
23 (0.1)
360 (2.5)
180 (1.3)
186 (1.3)
350 (2.5)
124 (0.9)
165 (1.2)
103 (0.7)
228 (1.6)
104 (0.7)
228 (1.6)
306 (2.2)
86 (0.6)
313 (2.3)
413 (3.0)
203 (1.5)
123 (0.9)
162 (1.2)
350 (2.5)
350 (2.5)
193 (1.4)
207 (1.5)
162 (1.2)
161 (1.2)
252 (1.8)
205 (1.5)
292 (2.0)
162 (1.2)
253 (1.8)
633 (4.6)
504 (3.6)
107 (0.8)
3
12
18
3
3
3
3
3
3
5
5
5
3
3
3
3
8
8
3
3
3
3
3
3
3
48
38
3
24
24
3
1 (429)
1 (166)
1 (113)
2 (380)
3 (78)
4 (134)
5 (115)
6 (231)
7 (88)
8 (205)
9 (389)
10 (93)
11 (348)
12 (440)
13 (217)
14 (146)
15 (103)
16 (173)
17 (385)
18 (250)
19 (212)
20 (215)
21 (180)
22 (285)
23 (242)
24 (226)
25 (129)
26 (284)
27 (214)
28 (118)
29 (137)
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
corresponding monosulfide (as monitored by TLC), was not
observed in benzoisothiazolones 1 and 3–29. 2-Iodo-arylamides
with alkyl groups such as methyl, n-butyl, phenylethyl, and cyclo-
hexyl successfully underwent S–N coupling reaction and gave
respective benzoisothiazolones quantitatively (entries 3–6). Also
arylamides having allyl group are compatible with copper catalyzed
S–N coupling reaction (entries 7 and 10). Synthesis of allyl bez-
oisothiazolone 7 proved to be difficult by the earlier reported meth-
ods. Gravace has isolated 7 in impure form.12b The synthesis of 7
from N-allyl-2-mercaptobenzamide was unsuccessful by using
phenyliodine (III)-bistrifluoroacetate reagent (Eq. 2).8 Synthesis of
allyl benzoisothiazolone 10 has been reported from 2-chloro-5-
nitroarylamide by using t-butylthiol as a sulfur source and finally
ring closure by trimethylsilyl chloride (Eq. 3).6b Sulfur–nitrogen
coupling reaction yielded allyl benzoisothiazolones 7 and 10 quan-
titatively from readily available substrates in one pot. We have also
studied nitro-substituted substrates in the S–N coupling reaction.
By exploiting CuI/L catalyst, not only 5-NO2 substituted but also
7-NO2 substituted S–N heterocycles (8–10) were obtained in good
to excellent yield (entries 8–10). 2-Iodo-arylamide substrates with
fluorine, chlorine, and bromine substituents were also tolerated in
the S–N coupling reaction and the reaction shows good selectivity
among chloro vs iodo and bromo versus iodo substituents within
the substrate (entries 13 and 14). Furthermore, substrates with
an additional acidic proton such as alcohol and amide (entries
15–18) also underwent S–N coupling reaction and the yield
remains unaffected. Substrates with methoxy and ester functional
groups are also amenable to the copper catalyzed coupling
reaction.
This coupling reaction was then extended to other aromatics
such as pyridyl and naphthyl substrates (entries 27–29). As ex-
pected, S–N coupling reaction occurred smoothly with the iodo-
naphthyl substrate and produced naphthyl S–N heterocycle 29
quantitatively. However, coupling reaction was sluggish on the

B. S. Bhakuni et al. / Tetrahedron Letters 53 (2012) 1354–1357
1357
Herrero, M. T. R.; Martin, S.; Domìnguez, E. Tetrahdron 2009, 65, 1500; (g) Gan,
J.; Ma, D. Org. Lett. 2009, 11, 2788; (h) Ma, D.; Xie, S.; Xue, P.; Zhang, X.; Dong, J.;
Jiang, Y. Angew. Chem. Int. Ed. 2009, 48, 4222; (i) Alves, D.; Santos, C.; Cayane,
G.; Paixao, M. W.; Marcio, W.; Soares, L. C.; Souza, D.; Rodrigues, O. E. D.; Braga,
A. L. Teterahedron Lett. 2009, 50, 6635; (j) Ma, D.; Geng, Q.; Zhang, H.; Jiang, Y.
Angew. Chem. Int. Ed. 2010, 49, 1291; (k) Shi, L.; Liu, X.; Zhang, H.; Jiang, Y.; Ma,
D. J. Org. Chem. 2011, 76, 4200; (l) Ma, D.; Lu, X.; Shi, L.; Zhang, H.; Jiang, Y.; Liu,
X. Angew. Chem. Int. Ed. 2011, 50, 1118.
readily accessible chloro-nicotinamides under optimized condi-
tions. The use of stoichiometric amount of CuI/L improved the yield
to a satisfactory level (40–60%).
A possible mechanistic pathway is depicted in Scheme 2, which
is similar to the earlier proposed mechanism.16 We believe that the
reaction proceeds via LCu–NR amide complex.20 Insertion of sulfur
into LCu–NR bond would lead to intermediate A, which could fur-
ther react intramolecularly to carbon–iodine, followed by reduc-
tive elimination to give benzoisothiazolone and regeneration of
CuIL complex. It is worth noting that the choice and amount of
base are important in the copper mediated S–N coupling reaction.
The use of excess of K2CO3 lowers the yield of benzoisothiazolone
1. It is evident from the Table 2 (vide supra) that most of the ben-
zoisothiazolones were obtained by employing 1.2–1.5 equiv of
K2CO3. Furthermore, strong bases such as K3PO4 and KOH were
found to be less effective for clean and complete conversion of sub-
strates. This is possibly due to the formation of cuprate intermedi-
ate B, which is presumably unreactive.20 This type of intermediate
could be expected in the case of electron rich 2-chloro/bromo-
arylamide substrates where carbon–chlorine bond is strong and
difficult to undergo sulfur–carbon coupling reaction (entries 24–
25, Table 1). High CuI/L complex loading would circumvent the for-
mation of intermediate B and therefore seems reasonable that high
CuI/L loading improves the yield satisfactorily in 2-chrloro-aryla-
mide substrates.
4. (a) Okachi, R.; Niino, H.; Kitaura, K.; Mineura, K.; Nakamizo, Y.; Murayama, Y.;
Ono, T.; Nakamizo, A. J. Med. Chem. 1985, 28, 1772; (b) Baggaley, K. H.; English,
P. D.; Jennings, L. J. A.; Morgan, B.; Nunn, B.; Tyrrell, A. W. R. J. Med. Chem. 1985,
28, 1661; (c) v Montfort, R. L. M.; Congreeve, M.; Tisi, D.; Carr, R.; Jhoti, H.
Nature 2003, 423, 773; (d) Gorsuch, S.; Bavetsias, V.; Rowlands, M. G.; Aherne,
G. W.; Workman, P.; Jarman, M.; McDonald, E. Bioorg. Med. Chem. 2009, 17, 467;
(e) Dahl, R.; Bravo, Y.; Sharma, V.; Ichikawa, M.; Dhanya, R.-P.; Hedrick, M.;
Brown, B.; Rascon, J.; Vicchiarelli, M.; M -Novo, A.; Yang, L.; Stonich, D.; Su, Y.;
Smith, L. H.; Sergienko, E.; Freeze, H. H.; Cosford, N. D. P. J. Med. Chem. 2011, 54,
3661.
5. (a) Sivaramakrishnan, S.; Keerthi, K.; Gates, K. S. J. Am. Chem. Soc. 2005, 127,
10830; (b) Sarma, B. K.; Mugesh, G. J. Am. Chem. Soc. 2007, 129, 8872; (c)
Brahemi, G.; Kona, F. R.; Fiasella, A.; Buac, B.; Soukupová, J.; Brancale, A.;
Burger, A. M.; Westwell, A. D. J. Med. Chem. 2010, 53, 2757.
6. (a) Villalobos, J. M.; Srogl, J.; Liebeskind, L. S. J. Am. Chem. Soc. 2007, 129, 15734;
(b) Henke, A.; Srogl, J. Chem. Commun. 2010, 46, 6819.
7. (a) Gialdi, F.; Ponci, R.; Barrufini, A. Farmaco Ed. Sci. 1961, 16, 509; (b) P.-Ottlik,
M.; Potaczek, P.; Piasecki, E.; Mlochowski, J. Molecules 2010, 15, 8214. and
references cited therein.
8. Correa, A.; Tellitu, I.; Domínguez, E.; Martin, R. S. Org. Lett. 2006, 8, 4811.
9. Henke, A.; Srogl, J. J. Org. Chem. 2008, 73, 7783.
10. (a) Wright, S. W.; Abelman, M. M.; Bostrom, L. L.; Corbett, R. L. Teterahedron
Lett. 1992, 33, 153; (b) Wright, S. W.; Petraitis, J. J.; Batt, D. G.; Corbett, R. L.;
Meo, S. V. D.; Freimark, B.; Giannaras, J. V.; Orwat, M. J.; Pinto, D. J.; Pratta, M.
A.; Sherk, S. R.; Stampfli, H. F.; Williams, J. M.; Magolda, R. L.; Arner, E. C. Bioorg.
Med. Chem. 1995, 3, 227; (c) Volonterio, A.; Bravo, P.; Zanda, M. Teterahedron
Lett. 2002, 43, 6537.
11. Honek, J. F.; Manchini, M. L.; Belleau, B. Synth. Commun. 1983, 13, 997.
12. (a) Grivas, J. C. Ger. Offen. Patent: DE 2119730, 1971 [Chem. Abstr. 1972, 76,
46193].; (b) Grivas, J. C. J. Org. Chem. 1975, 40, 2029.
In summary, we have presented a general, mild, and practical
method for the synthesis of benzo[d]isothiazol-3(2H)-ones and re-
lated sulfur–nitrogen heterocycles. The developed copper cata-
lyzed/mediated S–N coupling reaction system is tolerant to a
wide variety of functional groups. Biological studies on S–N hetero-
cycles are currently in progress in our laboratory.
13. Shimizu, M.; Sugano, Y.; Konakahara, T.; Gama, Y.; Shibuya, I. Tetrahedron 2002,
58, 3779.
14. (a) Jin, C. K.; Moon, J.-K.; Lee, W. S.; Nam, K. S. Synlett 2003, 1967; (b) Sano, T.;
Takagi, T.; Gama, Y.; Shibuya, I.; Shimizu, M. Synthesis 2004, 1585.
15. Engman, L.; Anders, H. J. Org. Chem. 1989, 54, 2964.
Acknowledgments
16. (a) Balkrishna, S. J.; Bhakuni, B. S.; Chopra, D.; Kumar, S. Org. Lett. 2010, 12,
5394; (b) Balkrishna, S. J.; Bhakuni, B. S.; Kumar, S. Tetrahedron 2011, 67, 9565.
17. (a) Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64, 670; (b) Murru, S.; Patel,
B. K.; Le Bras, J.; Muzart, J. J. Org. Chem. 2009, 74, 2217; (c) Sekar, R.; Srinivasan,
M.; Marcelis, At. M.; Sambandam, A. Tetrahedron Lett. 2011, 52, 3347; (d)
Murru, S.; Ghosh, H.; Sahoo, S. K.; Patel, B. K. Org. Lett. 2009, 11, 4254.
18. Synthesis of 2-benzylbenzo[d]isothiazol-3(2H)-one (1); A typical procedure.
Sulfur–nitrogen coupling reactions on 2-halo aryl amides were carried out
using mentioned amount of reagents and solvents in Table 2 (vide supra). In a
single neck flask (25 mL) containing DMF (5 mL), CuI (95 mg, 0.5 mmol) and
1,10-phenanthroline (90 mg, 0.5 mmol) were added and stirred for 15 min
under N2. After this, 2-iodo-N-benzylbenzamide (0.67 g, 2.0 mmol), sulfur
powder (80 mg, 2.4 mmol), and anhydrous K2CO3 powder (360 mg, 2.5 mmol)
were added in the same sequence, stirred for 15 min at room temperature and
then refluxed at 110 °C for 3 h under N2. After this, reaction mixture was
poured into brine solution (50 mL), stirred for 3 h, reaction mixture together
with brine was extracted with ethyl acetate (20 mL Â 3), dried over Na2SO4
(5.0 g), concentrated under vacuo to obtain brown color solid. Purification by
column chromatography using hexane/ethyl acetate (8:2) yielded white
colored crystalline solid. Yield 414 mg (89%), mp 79–80 °C (86–89 °C).6b,8 1H
NMR d 8.07 (d J = 8.0 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H),
7.39 (t, J = 7.5 Hz, 1H), 7.35–7.32 (m, 5H), 5.05 (s, 2H). 13C NMR d 165.4, 140.4,
136.2, 131.8, 128.8, 128.4, 128.3, 126.8, 125.5, 124.5, 120.4, 47.6. IR (plate):
3064, 2923, 1651, 1598, 1447, 1333, 1246, 1186, 1079 cmÀ1; ES-MS (ESI) m/z
242 (M+H+). Benzoisothiazolones (2–29) were purified by column
chromatography using hexane/EtOAc (8:2) for 2–14, 19–26, and 29; CH2Cl2/
MeOH (97:3) for 15–18, 27, and 28.
This study is financially supported by DST-New Delhi. BSB and
JBS thank IISER Bhopal for fellowship. SK thanks Professor Harkesh
B Singh and Dr. Vijay Pal (Department of Chemistry, IIT Bombay)
for mass and HRMS data collections. We are thankful to Dr. Deepak
Chopra for editing this manuscript.
Supplementary data
Supplementary data (references for 2-halo-arylamides (sub-
strates for the synthesis of S–N heterocycles), general experimental
details, characterization data, copies of NMR (1H and 13C), and
Mass spectra for compounds) associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2012.01.003.
References and notes
1. (a) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596; (b) Kumar, S.;
Engman, L. J. Org. Chem. 2006, 71, 5400; (c) Singh, D.; Deobald, A. M.; Camarago,
L. R. S.; Tabarellie, G.; Rodrigues, O. E. D.; Braga, A. L. Org. Lett. 2010, 12, 3288.
2. (a) Taniguchi, N. J. Org. Chem. 2004, 69, 6904; (b) Taniguchi, N.; Onami, T. J. Org.
Chem. 2004, 69, 915; (c) Taniguchi, N. Synlett 2005, 1185; (d) Taniguchi, N. J.
Org. Chem. 2006, 71, 7874; (e) Taniguchi, N. J. Org. Chem. 2007, 72, 1241; (f)
Taniguchi, N. Eur. J. Org. Chem. 2010, 2670; (g) Taniguchi, N. Tetrahedron 2009,
65, 2782; (h) Taniguchi, N. Synlett 2011, 1308.
3. (a) Jiang, Y.; Qin, Y.; Xie, S.; Zhang, X.; Dong, J.; Ma, D. Org. Lett. 2009, 11, 5250;
(b) Ke, F.; Qu, Y.; Jiang, Z.; Li, Z.; Wu, D.; Zhou, X. Org. Lett. 2011, 13, 454; (c)
Zeni, G. Teterahedron Lett. 2005, 46, 2647; (d) Carril, M.; Martin, R. S.;
Domìnguez, E.; Tellitu, I. Chem. Eur. J. 2007, 13, 5100; (e) Sharma, A.; Schwab,
R. S.; Braga, A.; Barcellos, T.; Paixao, M. W. Teterahedron Lett. 2008, 49, 5172; (f)
19. Characterization data for 2-phenylbenzo[d]isothiazol-3(2H)-one (2). Mp 139–
140 °C (139–140 °C).16 1H NMR d 8.07 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H),
7.77 (t, J = 7.5 Hz, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.56–7.50 (m, 3H), 7.38 (t,
J = 7.5 Hz, 1H). IR (plate): 2918, 1660, 1590, 1484, 1301, 1265, 1123 cmÀ1; ES-
MS (ESI) m/z 228.0 (M+H+).
20. (a) Klapars, A.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 7421. See
references therein on the mechanistic consideration on copper catalyzed
amidation reactions. (b) Cuprate intermediate B is proposed based on the Ref.
20a.