An effective synthesis of N-substituted 2-sulfenamoylbenzoates and 1,2-benzisothiazolin-3-ones that uses 1,2-benzisothiazolin-3-one as a leaving group

Article abstract of DOI:10.1016/S0040-4020(02)00329-0

N-Substituted 2-sulfenamoylbenzoates and 1,2-benzisothiazolin-3-ones were effectively synthesized by the substitution reaction between S-[2-(3-oxo-1,2-benzisothiazolinyl)]-2-mercaptobenzoates (2) and primary amines. The substitution reaction occurred on the sulfur atom of the 2-sulfenamoyl group of 2, and 1,2-benzisothiazolin-3-one behaved as a leaving group. The eliminated 1,2-benzisothiazolin-3-one could be reused as a starting material for the synthesis of 2. N,N-Disubstituted 2-sulfenamoylbenzoates were prepared by the reaction of 2 with secondary amines.

Full text of DOI:10.1016/S0040-4020(02)00329-0

TETRAHEDRON
Pergamon
Tetrahedron 58 ,2002) 3779±3783
An effective synthesis of N-substituted 2-sulfenamoylbenzoates
and 1,2-benzisothiazolin-3-ones that uses
1,2-benzisothiazolin-3-one as a leaving group
Masao Shimizu,a,p Yoshinori Sugano,b Takeo Konakahara,b Yasuo Gamaa and Isao Shibuyaa
aNational Institute of Advanced Industrial Science and Technology, Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
bDepartment of Industrial Chemistry, Faculty of Science and Technology, Science University of Tokyo, Noda, Chiba 278-8510, Japan
Received 8 January 2002;accepted 15 March 2002
AbstractÐN-Substituted 2-sulfenamoylbenzoates and 1,2-benzisothiazolin-3-ones were effectively synthesized by the substitution reaction
between S-[2-,3-oxo-1,2-benzisothiazolinyl)]-2-mercaptobenzoates ,2) and primary amines. The substitution reaction occurred on the sulfur
atom of the 2-sulfenamoyl group of 2, and 1,2-benzisothiazolin-3-one behaved as a leaving group. The eliminated 1,2-benzisothiazolin-3-one
could be reused as a starting material for the synthesis of 2. N,N-Disubstituted 2-sulfenamoylbenzoates were prepared by the reaction of 2
with secondary amines. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
the reaction of 2-sulfenamoylbenzoates ,1) with 1,2-benz-
isothiazolin-3-one ,4) ,Scheme 1). Because the reaction of
2a with sodium methoxide afforded a methyl sulfenate
derivative and 1,2-benzisothiazolin-3-one ,4),6 we expected
that the substitution reaction on the sulfur atom of the
2-mercapto group of 2 would also occur with various
other nucleophiles. Therefore, we herein investigated the
reaction of 2 with amines for the synthesis of N-substituted
2-sulfenamoylbenzoates that could serve as starting
materials for the preparation of N-substituted 1,2-benziso-
thiazolin-3-ones, and we report the results herein.
It has been reported that sulfenamide derivatives are impor-
tant in the rubber industry, agriculture, and medicinal
applications.1 1,2-Benzisothiazolin-3-ones, which can be
regarded as cyclic sulfenamide compounds, have also
shown various fungistatic, antimicrobial, and antipsychotic
bioactivities.2 The most common method employed for the
formation of the N±S bonds in sulfenamides and 1,2-benz-
isothiazolin-3-ones is the reaction of amines with sulfenyl
chlorides.1,2a,3,4a Although sulfenyl chlorides are usually
prepared by chlorination of disul®des or thiols with
chlorine,4b the use of chlorine in the laboratory is sometimes
restricted because it is dif®cult to handle. N-Sulfenyl hetero-
cycles could replace sulfenyl chloride as starting materials
for the preparation of the sulfenamides because these
heterocycles are good leaving groups;5 however, N-sulfenyl
heterocycles are also prepared from sulfenyl halides.
2. Results and discussion
First we examined the reaction of 2 with substituted
anilines, and the results are shown in Table 1. When 2a
was treated with p-methylaniline in methanol for 7.5 h at
In a previous paper, we reported a convenient synthesis of
1,2-benzisothiazolin-3-ones by the cyclization of 2-sulf-
enamoylbenzoates.6 During this investigation, we found
that heating methyl 2-sulfenamoylbenzoate ,1a) in toluene
at 1008C gave methyl S-[2-,3-oxo-1,2-benzisothiazolinyl)]-
2-mercaptobenzoate ,2a) in a good yield. In a subsequent
paper,7 we showed that transamination occurred on the
sulfur atom of 1 and that S-[2-,3-oxo-1,2-benzisothiazo-
linyl)]-2-mercaptobenzoates ,2) could also be prepared by
Keywords: amines;benzisothiazoles;substitution;sulfenic acids and
derivatives.
p
Corresponding author. Tel.: 181-298-61-4575;fax: 181-298-61-4487;
e-mail: m.shimizu@aist.go.jp
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,02)00329-0

3780
M. Shimizu et al. / Tetrahedron 58 12002) 3779±3783
Table 1. Reactions of 2 with anilines
Entry
2
R2
Temperature
Time ,h)
Product
Yielda ,%)
Yielda ,%) of 4
1
2
3
4
5
6
7
2a
2a
2a
2a
2a
2a
2b
MeO
Me
Me
H
Cl
Cl
Re¯ux
rt
1.5
7.5
3
3
3
3a
3b
3b
3c
3d
3d
5
97
83
90
94
31
63
99
71
66
47
65
44
61
60
Re¯ux
Re¯ux
Re¯ux
Re¯ux
Re¯ux
10
3
Me
2, 0.4 mmol;aniline, 0.5 mmol;MeOH, 10 mL.
Isolated yield.
a
Scheme 2.
room temperature, methyl 2-[N-,p-methylphenyl)sulfena-
moyl]benzoate ,3b) and 1,2-benzisothiazolin-3-one ,4)
were obtained in good yields ,entry 2). This result showed
that transamination occurred between the aniline and 4 on
the sulfur atom of the 2-mercapto group of 2. When this
reaction was carried out in re¯uxing methanol for 3 h, the
yield of 3b increased ,entry 3). With various other anilines,
substitution reactions gave N-substituted 2-sulfenamoyl-
benzoates ,3 and 5) and the eliminated 1,2-benzisothiazo-
lin-3-one ,4). Because 2b was prepared by means of the
reaction of 1b with 4, the isolated 4 could be used as the
starting material for 2b ,Scheme 2).
3d in satisfactory yield ,entry 6). In the case of p-cyano-
aniline, the reaction had not proceeded at all after 3 h, and
2a was recovered. In all cases, the products were N-substi-
tuted 2-sulfenamoylbenzoates ,3 and 5), and N-substituted
1,2-benzisothiazolin-3-ones ,6) were not formed even when
the reaction time was increased. To obtain N-substituted
1,2-benzisothiazolin-3-ones ,6), we had to treat the sulfena-
mides with base, as has been reported in the literature.8
Treatment of 3 or 5 with sodium methoxide in methanol
resulted in the cyclization of the N-substituted sulfenamides,
and N-substituted 1,2-benzisothiazolin-3-ones ,6) were
obtained in good yields. The results are shown in Table 2.
When we attempted the direct cyclization of 2a to 6b by
treating 2a with p-methylaniline in the presence of sodium
methoxide, we obtained a complicated mixture of reaction
products and no 6b was isolated. However, we did achieve a
one-pot synthesis of 6b from 2a by ®rst heating 2a and p-
methylaniline in re¯uxing methanol for 4.5 h, and then
adding sodium methoxide;heating the reaction mixture at
re¯ux for an additional 1 h gave 6b in 60% yield.
When 2a was treated with p-chloroaniline, which have weak
nucleophilicity, the yields of 3d and 4 were low and the
amount of unreacted starting material 2a increased ,entry
5). Therefore, long reaction time was required to synthesize
Table 2. Synthesis of N-substituted 1,2-benzisothiazolin-3-ones ,6) from
N-substituted sulfenamides ,3 and 5)
We next investigated the reaction of 2a with aliphatic
amines, and the results are summarized in Table 3. The
treatment of 2a with benzylamine in methanol at re¯ux
afforded a mixture of methyl 2-,N-benzylsulfenamoyl)-
benzoate ,3e) and 2-benzyl-1,2-benzisothiazolin-3-one
,6e), along with eliminated 1,2-benzisothiazolin-3-one ,4)
,entry 13). When the reaction was carried out in toluene at
1008C, the corresponding benzisothiazolin-3-one ,6e) was
obtained in quantitative yield ,entry 15). Reactions of
2a with various aliphatic amines were also carried out.
Sterically hindered amines gave only N-substituted sulfena-
mides, and cyclization to 1,2-benzisothiazolin-3-ones did
Entry
Sulfenamide
R2
Product
Yielda ,%)
8
9
10
11
3a
3b
3c
5
MeO
Me
H
6a
6b
6c
6b
69
88
76
69
Me
Sulfenamide ,3 or 5), 0.8 mmol;NaOMe, 0.1 mmol;MeOH, 5 mL.
Isolated yield.
a

M. Shimizu et al. / Tetrahedron 58 12002) 3779±3783
3781
Table 3. Reactions of 2a with aliphatic amines
Entry
R3
R4
Temperature
Time ,h)
3
Yielda ,%) of 3
6
Yielda ,%) of 6
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
PhCH2
PhCH2
PhCH2
PhCH2
p-ClC6H4CH2
p-ClC6H4CH2
p-MeOC6H4CH2
Pr
HO,CH2)2
HO,CH2)3
cyclo-Pr
t-Bu
PhMe2C
Et
H
rt
5
3
5.5
3
3
3
3
3
3
3
3
3
3
3
3
3
3e
3e
3e
70
52
23
H
H
H
H
H
H
H
H
H
H
H
H
Et
Re¯ux
Re¯ux
1008Cb
Re¯ux
1008Cb
1008Cb
808Cc
Re¯ux
Re¯ux
808Cc
808Cc
Re¯ux
808Cc
Re¯ux
Re¯ux
6e
6e
6e
6f
44
60
100
38
99
99
98
90
69
82
3f
58
6f
6g
6h
6i
6j
6k
3l
82
85
66
79
67
3m
3n
3o
3p
±,CH2)4±
±,CH2)2±O±,CH2)2±
2a, 0.4 mmol;amine, 0.5 mmol;MeOH, 10 mL.
Isolated yield.
a
b
Reaction carried out in toluene.
Reaction carried out in a sealed tube.
c
not occur ,entries 23 and 24). The eliminated 4 was more
dif®cult to isolate in pure form from the reactions shown in
Table 3 than from the reactions with anilines. The aliphatic
amines, which are more basic than anilines, formed salts
with 4. This was especially true for the reaction with
2-hydroxyethylamine ,entry 20): a salt with a formula of
C9H12N2O2S precipitated after the reaction. Secondary
amines were also utilized for the same substitution reactions
with 2, and N,N-disubstituted sulfenamides ,3) were
obtained in good yields ,entries 25±27).
Varian Gemini 300 BB ,300 MHz) spectrometer with tetra-
methylsilane as an internal standard. IR spectra were
recorded on a JASCO FTIR-5300 spectrophotometer.
4.2. Materials
Methyl S-[2-,3-oxo-1,2-benzisothiazolinyl)]-2-mercapto-
benzoate ,2a) was synthesized by heating methyl 2-sulfena-
moylbenzoate ,1a) in toluene, and ethyl S-[2-,3-oxo-1,2-
benzisothiazolinyl)]-2-mercaptobenzoate was synthesized
by heating ethyl 2-sulfenamoylbenzoate ,1b) with 1,2-benz-
isothiazolin-3-one ,4) in toluene as reported in our previous
papers.6,7
3. Conclusion
The 2-,3-oxo-1,2-benzisothiazolinyl) group in S-[2-,3-oxo-
1,2-benzisothiazolinyl)]-2-mercaptobenzoates ,2) was easily
replaced with various amines to yield N-substituted 2-sulf-
enamoylbenzoates or N-substituted 1,2-benzisothiazolin-3-
ones, which indicates that 2 is a useful intermediate for the
synthesis of N-substituted 2-sulfenamoylbenzoates and
N-substituted 1,2-benzisothiazolin-3-ones. The eliminated
1,2-benzisothiazolin-3-one ,4) could be reused for the
synthesis of 2.
4.3. General procedure for reaction of 2 with anilines
To a solution of 2 ,0.4 mmol) in methanol ,10 mL) was
added an aniline ,0.5 mmol), and reaction was carried out
under the conditions as described in Table 1. After the reac-
tion, the solvent was evaporated and a crude reaction
mixture was chromatographed on silica gel with CH2Cl2
as eluent to isolate 3 or 5, then with CH2Cl2±acetone±
methanol ,100:40:8) mixture as eluent to isolate 4. The
product was recrystallized from appropriate solvent.
4. Experimental
4.1. General
4.3.1. Methyl 2-[N-+p-methoxyphenyl)sulfenamoyl]-
benzoate +3a). Mp 106.5±1088C ,CH2Cl2±MeOH) ,lit.8
106±1078C); H NMR ,CDCl3) d 3.75 ,3H, s), 3.95 ,3H,
1
Mps were determined on a Mettler FP90 microscope plate,
and are uncorrected. 1H NMR spectra were obtained with a
s), 4.90 ,1H, br s), 6.79 ,2H, d, Jˆ9.1 Hz), 6.92 ,2H, d,
Jˆ9.1 Hz), 7.16 ,1H, ddd, Jˆ8.2, 6.7, 1.1 Hz), 7.42 ,1H,

3782
M. Shimizu et al. / Tetrahedron 58 12002) 3779±3783
td, Jˆ7.3, 1.4 Hz), 7.52 ,1H, dd, Jˆ8.2, 1.4 Hz), 8.04 ,1H,
dd, Jˆ8.1, 1.1 Hz);IR ,KBr) nmax 3347, 1692, 1508, 1273,
,1H, ddd, Jˆ8.0, 6.9, 1.1 Hz), 8.11 ,1H, dt, Jˆ8.0, 1.1 Hz);
IR ,KBr) nmax 1642, 1505, 1447, 1331, 1127, 750 cm21
.
1242, 820, 741 cm21
.
4.4.3. 2-Phenyl-1,2-benzisothiazolin-3-one +6c). Mp 138±
1408C ,EtOH) ,lit.8 142±143.58C); 1H NMR ,CDCl3) d 7.33
,1H, t, Jˆ7.7 Hz), 7.43±7.51 ,3H, m), 7.59 ,1H, d, Jˆ
8.2 Hz), 7.65±7.73 ,3H, m), 8.11 ,1H, dd, Jˆ8.0, 1.1 Hz);
IR ,KBr) nmax 1663, 1591, 1491, 1445, 1325, 1304, 764,
4.3.2. Methyl 2-[N-+p-methylphenyl)sulfenamoyl]benzo-
ate +3b). Mp 131.5±1328C ,CH2Cl2±hexane); 1H NMR
,CDCl3) d 2.25 ,3H, s), 3.95 ,3H, s), 4.99 ,1H, br s), 6.88
,2H, d, Jˆ8.5 Hz), 7.02 ,2H, d, Jˆ8.5 Hz), 7.15 ,1H, td,
Jˆ7.5, 0.8 Hz), 7.40 ,1H, ddd, Jˆ8.2, 7.5, 1.5 Hz), 7.50
,1H, dd, Jˆ8.2, 0.8 Hz), 8.03 ,1H, dd, Jˆ7.8, 1.5 Hz);IR
,KBr) nmax 3343, 1692, 1510, 1435, 1275, 1238, 905, 812,
745 cm21;Anal. calcd for C 15H15NO2S: C, 65.91;H, 5.53;
N, 5.12. Found: C, 65.87;H, 5.46;N, 5.01.
733 cm21
.
4.5. General procedure for reaction of 2a with aliphatic
amines
4.3.3. Methyl 2-+N-phenylsulfenamoyl)benzoate +3c). Mp
152.5±1548C ,MeOH) ,lit.8 154±155.58C); 1H NMR
,CDCl3) d 3.96 ,3H, s), 5.08 ,1H, br s), 6.87 ,1H, t, Jˆ
7.3 Hz), 6.97±7.00 ,2H, m), 7.14±7.25 ,3H, m), 7.41 ,1H,
td, Jˆ7.7, 1.4 Hz), 7.50 ,1H, dd, Jˆ8.2, 1.1 Hz), 8.05 ,1H,
dd, Jˆ8.1, 1.4 Hz);IR ,KBr) nmax 3333, 1696, 1437, 1277,
To a solution of 2a ,127 mg, 0.4 mmol) in methanol
,10 mL) was added an aliphatic amine ,0.5 mmol), and reac-
tion was carried out under the conditions as described in
Table 3. After the reaction, the solvent was evaporated
and a crude reaction mixture was chromatographed on silica
gel with CH2Cl2 as eluent to isolate 3, then with CH2Cl2±
acetone±methanol ,100:5:1) mixture as eluent to isolate
6, and then with CH2Cl2±acetone±methanol ,100:40:8)
mixture as eluent to isolate 4. The product was recrystal-
lized from appropriate solvent.
1233, 855, 748 cm21
.
4.3.4. Methyl 2-[N-+p-chlorophenyl)sulfenamoyl]benzo-
ate +3d). Mp 154±1558C ,CH2Cl2±hexane) ,lit.8 152±
1538C); H NMR ,CDCl3) d 3.96 ,3H, s), 5.09 ,1H, br s),
1
6.90±6.93 ,2H, m), 7.15±7.22 ,3H, m), 7.42±7.44 ,2H, m),
8.05 ,1H, dt, Jˆ7.4, 1.0 Hz);IR ,KBr) nmax 3352, 3329,
4.5.1. Methyl 2-+N-benzylsulfenamoyl)benzoate +3e). Oil
1
,lit.8 mp 61±62.58C); H NMR ,CDCl3) d 2.88 ,1H, br t),
1690, 1491, 1275, 905, 826, 743 cm21
.
3.91 ,3H, s), 4.13 ,2H, d, Jˆ5.2 Hz), 7.17 ,1H, td, Jˆ1.0,
8.0 Hz), 7.26±7.42 ,5H, m), 7.56 ,1H, ddd, Jˆ8.2, 7.1,
1.4 Hz), 7.90 ,1H, dd, Jˆ8.2, 1.1 Hz), 8.02 ,1H, dd,
Jˆ8.0, 1.4 Hz);IR ,neat) nmax 3337, 1707, 1271, 1055,
4.3.5. Ethyl 2-[N-+p-methylphenyl)sulfenamoyl]benzoate
+5). Mp 101±102.58C ,CH2Cl2±hexane); 1H NMR ,CDCl3)
d 1.43 ,3H, t, Jˆ7.1 Hz), 2.26 ,3H, s), 4.42 ,2H, q, Jˆ
7.1 Hz), 4.98 ,1H, br s), 6.89 ,2H, d, Jˆ8.5 Hz), 7.02 ,2H,
d, Jˆ8.5 Hz), 7.16 ,1H, ddd, Jˆ8.0, 7.7, 1.1 Hz), 7.40 ,1H,
td, Jˆ7.7, 1.4 Hz), 7.50 ,1H, dd, Jˆ8.2, 1.1 Hz), 8.06 ,1H,
dd, Jˆ7.7, 1.4 Hz);IR ,KBr) nmax 3356, 1690, 1512, 1269,
1248, 1098, 810, 745 cm21;Anal. calcd for C 16H17NO2S: C,
66.87;H, 5.96;N, 4.87. Found: C, 66.73;H, 5.86;N, 4.71.
745 cm21
.
4.5.2. 2-Benzyl-1,2-benzisothiazolin-3-one +6e). Mp 85.5±
1
878C ,isopropanol) ,lit.8 86±898C); H NMR ,CDCl3) d
5.06 ,2H, s), 7.34±7.43 ,6H, m), 7.49 ,1H, dd, Jˆ8.2,
0.8 Hz), 7.59 ,1H, ddd, Jˆ8.2, 7.1, 1.1 Hz), 8.07 ,1H, dd,
Jˆ8.0, 1.1 Hz);IR ,KBr) nmax 1667, 1447, 1337, 1244,
750 cm21
.
4.4. General procedure for synthesis of N-substituted
1,2-benzisothiazolin-3-one +6) from 3 or 5
4.5.3. Methyl 2-[N-+p-chlorobenzyl)sulfenamoyl]benzo-
ate +3f). Oil; H NMR ,CDCl3) d 2.93 ,1H, br t), 3.90
1
,3H, s), 4.09 ,2H, d, Jˆ5.8 Hz), 7.17 ,1H, ddd, Jˆ7.7,
7.1, 1.1 Hz), 7.31 ,4H, s), 7.55 ,1H, ddd, Jˆ8.2, 7.1,
1.4 Hz), 7.84 ,1H, dd, Jˆ8.2, 1.1 Hz), 8.02 ,1H, dd, Jˆ
7.7, 1.4 Hz);IR ,neat) nmax 3329, 1705, 1271, 1100,
745 cm21;HRMS calcd for C 15H14ClNO2S: 307.0434.
Found: 307.0447.
To a solution of sodium methoxide ,0.03 mmol) in methanol
,5 mL) was added N-substituted sulfenamide ,3 or 5)
,0.8 mmol) at re¯ux and the mixture was stirred for 1 h.
The solvent was evaporated and a crude reaction mixture
was chromatographed on silica gel with CH2Cl2±ethyl
acetate ,10:1) mixture as eluent. The product was recrystal-
lized from appropriate solvent.
4.5.4. 2-+p-Chlorobenzyl)-1,2-benzisothiazolin-3-one +6f).
Mp 83.4±84.48C ,EtOH) ,lit.10 86±898C); 1H NMR ,CDCl3)
d 5.02 ,2H, s), 7.28±7.35 ,4H, m), 7.42 ,1H, ddd, Jˆ8.0,
7.2, 1.0 Hz), 7.51 ,1H, dt, Jˆ8.0, 0.8 Hz), 7.61 ,1H, ddd,
Jˆ8.0, 7.2, 1.0 Hz), 8.07 ,1H, ddd, Jˆ8.0, 1.0, 0.8 Hz);IR
4.4.1. 2-+p-Methoxyphenyl)-1,2-benzisothiazolin-3-one
1
+6a). Mp 147±1488C ,EtOH) ,lit.8 147±1498C); H NMR
,CDCl3) d 3.84 ,3H, s), 6.98 ,2H, d, Jˆ9.2 Hz), 7.44 ,1H,
td, Jˆ7.6, 1.2 Hz), 7.54 ,2H, d, Jˆ9.2 Hz), 7.57 ,1H, d,
Jˆ8.3 Hz), 7.65 ,1H, ddd, Jˆ8.3, 7.6, 1.1 Hz), 8.09 ,1H,
dd, Jˆ7.6, 1.1 Hz);IR ,KBr) nmax 1659, 1507, 1443, 1242,
,KBr) nmax 1651, 1597, 1487, 1331, 1090, 731, 584 cm21
.
4.5.5. 2-+p-Methoxybenzyl)-1,2-benzisothiazolin-3-one
+6g). Mp 75.2±76.38C ,EtOH); H NMR ,CDCl3) d 3.80
1
1019, 839, 749 cm21
.
,3H, s), 5.00 ,2H, s), 6.89 ,2H, d, Jˆ8.7 Hz), 7.31 ,2H, d,
Jˆ8.7 Hz), 7.40 ,1H, ddd, Jˆ8.0, 6.9, 0.8 Hz), 7.48 ,1H, dd,
Jˆ8.0, 0.8 Hz), 7.58 ,1H, ddd, Jˆ8.0, 6.9, 1.2 Hz), 8.06
,1H, dd, Jˆ8.0, 1.2 Hz);IR ,KBr) nmax 1672, 1514, 1445,
1335, 1254, 1020, 737 cm21;Anal. calcd for C 15H13NO2S:
4.4.2. 2-+p-Methylphenyl)-1,2-benzisothiazolin-3-one +6b).
Mp 136.7±137.18C ,benzene±hexane) ,lit.9 136±1378C);
1H NMR ,CDCl3) d 2.39 ,3H, s), 7.28 ,2H, d, Jˆ8.2 Hz),
7.45 ,1H, ddd, Jˆ8.0, 6.9, 1.1 Hz), 7.55±7.60 ,3H, m), 7.66

M. Shimizu et al. / Tetrahedron 58 12002) 3779±3783
3783
C, 66.40;H, 4.83;N, 5.16. Found: C, 66.30;H, 4.76;N,
5.07.
1.4 Hz), 8.26 ,1H, dd, Jˆ8.2, 0.8 Hz);IR ,KBr) nmax
3304, 1692, 1435, 1273, 1101, 750, 698 cm21;Anal. calcd
for C17H19NO2S: C, 67.74;H, 6.35;N, 4.65. Found: C,
67.57;H, 6.31;N, 4.57.
4.5.6. 2-Propyl-1,2-benzisothiazolin-3-one +6h). Oil ,lit.8
bp 126±1288C/0.2 mmHg); 1H NMR ,CDCl3) d 0.99 ,3H, t,
Jˆ7.3 Hz), 1.80 ,2H, hex, Jˆ7.3 Hz), 3.87 ,2H, t, Jˆ
7.3 Hz), 7.40 ,1H, ddd, Jˆ7.9, 7.0, 0.9 Hz), 7.55 ,1H, d,
Jˆ7.9 Hz), 7.60 ,1H, ddd, Jˆ7.9, 7.0, 1.2 Hz), 8.04 ,1H,
dt, Jˆ7.9, 0.9 Hz);IR ,neat) nmax 1657, 1447, 1333,
4.5.12. Methyl 2-+N,N-diethylsulfenamoyl)benzoate +3n).
Oil; 1H NMR ,CDCl3) d 1.16 ,6H, t, Jˆ7.1 Hz), 3.07 ,4H, q,
Jˆ7.1 Hz), 3.91 ,3H, s), 7.11 ,1H, ddd, Jˆ7.7, 7.1, 1.1 Hz),
7.49 ,1H, ddd, Jˆ8.2, 7.1, 1.4 Hz), 7.94 ,1H, dd, Jˆ8.2,
1.1 Hz), 8.00 ,1H, dd, Jˆ7.7, 1.1 Hz);IR ,neat) nmax
1711, 1458, 1435, 1269, 745 cm21;HRMS calcd for
C12H17NO2S: 239.0980;Found: 239.1005.
741 cm21
.
4.5.7. 2-+2-Hydroxyethyl)-1,2-benzisothiazolin-3-one +6i).
This compound was puri®ed with chromatography on silica
gel with CH2Cl2±acetone±methanol ,100:20:4) mixture as
eluent. Mp 112±112.58C ,ethyl acetate) ,lit.8 112±1148C);
1H NMR ,CDCl3) d 3.97 ,2H, td, Jˆ4.9, 1.1 Hz), 4.05 ,2H,
td, Jˆ4.9, 1.1 Hz), 7.40 ,1H, ddd, Jˆ8.0, 6.9, 1.1 Hz), 7.54
,1H, dt, Jˆ8.0, 1.4 Hz), 7.62 ,1H, ddd, Jˆ8.0, 6.9, 1.4 Hz),
8.03 ,1H, dt, Jˆ8.0, 1.1 Hz);IR ,KBr) nmax 3331, 1632,
1454, 1345, 1080, 748 cm21. A 2-hydroxyethylammonium
salt of 4 precipitated after the reaction. The salt, mp 143±
4.5.13. Methyl S-pyrrolidino-2-mercaptobenzoate +3o).
Mp 43.5±44.48C ,hexane); H NMR ,CDCl3) d 1.93±1.97
1
,4H, m), 3.18±3.22 ,4H, m), 3.91 ,3H, s), 7.12 ,1H, ddd,
Jˆ7.4, 7.1, 1.4 Hz), 7.50 ,1H, ddd, Jˆ8.2, 7.1, 1.6 Hz), 7.71
,1H, dd, Jˆ8.2, 1.1 Hz), 8.01 ,1H, dd, Jˆ7.4, 1.6 Hz);IR
,KBr) nmax 1709, 1458, 1439, 1269, 745 cm21;HRMS calcd
for C12H15NO2S: 237.0823. Found: 237.0817.
1
4.5.14. Methyl S-morpholino-2-mercaptobenzoate +3p).
Mp 104±1058C ,hexane); H NMR ,CDCl3) d 3.08 ,4H, t,
144.58C ,EtOH); H NMR ,CD3OD) d 2.94 ,2H, t, Jˆ
1
5.5 Hz), 3.70 ,2H, t, Jˆ5.5 Hz), 7.32 ,1H, ddd, Jˆ8.0,
7.1, 0.8 Hz), 7.48 ,1H, ddd, Jˆ8.2, 7.1, 1.4 Hz), 7.69 ,1H,
dt, Jˆ8.2, 0.8 Hz), 7.92 ,1H, ddd, Jˆ8.0, 1.4, 0.8 Hz);IR
,KBr) nmax 2861, 1470, 1431, 1076, 743 cm21;Anal. calcd
for C9H12N2O2S: C, 50.93;H, 5.69;N, 13.20. Found: C,
51.04;H, 5.73;N, 13.07.
Jˆ4.7 Hz), 3.82 ,4H, t, Jˆ4.7 Hz), 3.91 ,3H, s), 7.17 ,1H,
td, Jˆ6.6, 1.1 Hz), 7.55 ,1H, td, Jˆ7.1, 1.4 Hz), 8.01±8.05
,2H, m);IR ,KBr) nmax 1709, 1458, 1433, 1269, 745 cm21
Anal. calcd for C12H15NO3S: C, 56.90;H, 5.97;N, 5.53.
Found: C, 57.04;H, 5.94;N, 5.48.
;
4.5.8. 2-+3-Hydroxypropyl)-1,2-benzisothiazolin-3-one
+6j). This compound was puri®ed with chromatography on
silica gel with CH2Cl2±acetone±methanol ,100:20:4)
mixture as eluent. Mp 76.6±77.48C ,ethyl acetate) ,lit.10
74±758C); 1H NMR ,CDCl3) d 1.92 ,2H, tt, Jˆ6.2,
5.6 Hz), 3.58 ,2H, t, Jˆ5.6 Hz), 3.65 ,1H, br s), 4.08 ,2H,
t, Jˆ6.2 Hz), 7.44 ,1H, ddd, Jˆ8.0, 7.0, 1.1 Hz), 7.58 ,1H,
dt, Jˆ8.0, 1.1 Hz), 7.65 ,1H, td, Jˆ7.8, 1.1 Hz), 8.05 ,1H,
dt, Jˆ7.8, 1.1 Hz);IR ,KBr) nmax 3364, 2944, 1632, 1445,
References
1. Craine, L.;Raban, M. Chem. Rev. 1989, 89, 689±712.
2. ,a) Davis, M. Adv. Heterocycl. Chem. 1972, 14, 58±63.
,b) Pain, D. L.;Peart, B. J.;Wooldridge, K. R. H. Compre-
hensive Heterocyclic Chemistry;Potts, K. T., Ed.;Pergamon:
Oxford, 1984;Vol. 6, p. 175. ,c) Chapman, R. F.;Peart, B. J.
Comprehensive Heterocyclic Chemistry II;Shinkai, I., Ed.;
Pergamon: Oxford, 1996;Vol. 3, pp. 371±372.
1350, 1192, 1065, 937, 743 cm21
.
3. Schubart, R. 5th ed, Methoden der Organischen Chemie
1Houben-Weyl);Klamann, C., Ed.;Georg Thiem Verlag:
Stuttgart, 1985;Vol. 11E, pp. 107±122.
4.5.9. 2-Cyclopropyl-1,2-benzisothiazolin-3-one +6k).
Oil; H NMR ,CDCl3) d 1.05±1.12 ,4H, m), 3.10±3.17
1
4. ,a) Drabowicz, J.;Kielbasin'ski, P.;Mitolajczyk, M. In The
Chemistry of Sulphenic Acids and Their Derivatives, Patai, S.,
Ed.;Wiley: Chichester, 1990;pp. 255±286. ,b) Drabowicz, J.;
Kielbasin'ski, P.;Mitolajczyk, M. In The Chemistry of
Sulphenic Acids and Their Derivatives, Patai, S., Ed.;Wiley:
Chichester, 1990;pp. 223±254.
,1H, m), 7.38 ,1H, ddd, Jˆ8.0, 6.9, 1.1 Hz), 7.50 ,1H, dt,
Jˆ8.0, 0.8 Hz), 7.60 ,1H, ddd, Jˆ8.0, 6.9, 1.4 Hz), 8.01
,1H, ddd, Jˆ8.0, 1.4, 0.8 Hz);IR ,neat) nmax 1657, 1449,
1333, 741, 673 cm21;HRMS calcd for C 10H9NOS:
191.0405. Found: 191.0363.
5. ,a) Harpp, D. N.;Back, T. G. Tetrahedron Lett. 1971, 4953±
4956. ,b) Sosnovsky, G.;Krogh, J. A. Synthesis 1979, 228±
230. ,c) Romani, S.;Bovermann, G.;Moroder, L.;Wu Ènsch, E.
Synthesis 1985, 512±513. ,d) Tanaka, T.;Azuma, T.;Fang,
X.;Uchida, S.;Iwata, C.;Ishida, T.;In, Y.;Maezaki, N.
Synlett 2000, 33±36.
4.5.10. Methyl 2-[N-+tert-butyl)sulfenamoyl]benzoate
+3l). Mp 89±89.78C ,CH2Cl2±hexane); H NMR ,CDCl3)
1
d 1.22 ,9H, s), 2.55 ,1H, br s), 3.92 ,3H, s), 7.10 ,1H, td,
Jˆ7.8, 1.1 Hz), 7.50 ,1H, ddd, Jˆ8.4, 7.1, 1.4 Hz), 7.98
,1H, dd, Jˆ7.8, 1.4 Hz), 8.16 ,1H, dd, Jˆ8.4, 1.1 Hz);IR
,KBr) nmax 3291, 2961, 1701, 1433, 1269, 748 cm21;Anal.
calcd for C12H17NO2S: C, 60.22;H, 7.16;N, 5.85. Found: C,
60.33;H, 7.18;N, 5.76.
6. Shimizu, M.;Kikumoto, H.;Konakahara, T.;Gama, Y.;
Shibuya, I. Heterocycles 1999, 51, 3005±3012.
7. Shimizu, M.;Takagi, T.;Shibakami, M.;Gama, Y.;Shibuya,
I. Heterocycles 2000, 53, 2803±2808.
4.5.11. Methyl 2-[N-+1-methyl-1-phenylethyl)sulfena-
moyl]benzoate +3m). Mp 138.5±1408C ,benzene±hexane);
1H NMR ,CDCl3) d 1.58 ,6H, s), 3.07 ,1H, br s), 3.89 ,3H,
s), 7.12 ,1H, td, Jˆ7.1, 1.1 Hz), 7.23±7.28 ,1H, m), 7.34±
7.39 ,2H, m), 7.51±7.57 ,3H, m), 7.98 ,1H, dd, Jˆ7.7,
8. Grivas, J. C. J. Org. Chem. 1975, 40, 2029±2032.
9. Kamigata, N.;Hashimoto, S.;Kobayashi, M.;Nakanishi, H.
Bull. Chem. Soc. Jpn 1985, 58, 3131±3136.
10. Fischer, R.;Hurni, H. Arzneim-Forsch 1964, 14, 1301±1306.