Synthesis of 1,2-benzisothiazolin-3-one by transamination of sulfenamides

Article abstract of DOI:10.3987/COM-03-9809

N-Substituted sulfenamoylbenzoates were synthesized by transamination of N-unsubstituted sulfenamoylbenzoates with amines. The reaction did not always proceed by simple amine exchange between the amines and ammonia on the sulfur atom of the sulfenamides. In reactions with aliphatic amines, the sulfenamides cyclized to form N-substituted 1,2-benzisothiazolin-3-ones. The synthesis of 1,2-benzisothiazolin-3-ones by intramolecular transamination was also investigated by S-amination of 2-mercaptobenzamides.

Full text of DOI:10.3987/COM-03-9809

HETEROCYCLES, Vol. 60, No. 8, 2003
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HETEROCYCLES, Vol. 60, No. 8, 2003, pp. 1855 - 1864
Received, 15th May, 2003, Accepted, 8th July, 2003, Published online, 15th July, 2003
SYNTHESIS OF 1,2-BENZISOTHIAZOLIN-3-ONE
BY TRANSAMINATION OF SULFENAMIDES
Masao Shimizu,*a Ayanobu Takeda,a Hidenori Fukazawa,b Yoshimoto Abe,b
and Isao Shibuyaa
aNational Institute of Advanced Industrial Science and Technology (AIST),
Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan and
bDepartment of Industrial Chemistry, Faculty of Science and Technology, Tokyo
University of Science, Yamazaki, Noda, Chiba 278-8510, Japan
Abstract
–
N-Substituted sulfenamoylbenzoates were synthesized by
transamination of N-unsubstituted sulfenamoylbenzoates with amines. The
reaction did not always proceed by simple amine exchange between the amines
and ammonia on the sulfur atom of the sulfenamides. In reactions with aliphatic
amines,
the
sulfenamides
cyclized
to
form
N-substituted
1,2-benzisothiazolin-3-ones. The synthesis of 1,2-benzisothiazolin-3-ones by
intramolecular transamination was also investigated by S-amination of
2-mercaptobenzamides.
The synthesis of 1,2-benzisothiazolin-3-ones and their derivatives is of widespread interest owing to their
high antibacterial and antifungal activity.1,2 Typically, in the synthesis of these compounds, thiosalicylic
acid derivatives are converted to sulfenyl halides with chlorine or bromine, and subsequent treatment of
the products with amines forms the N–S bonds.1,3,4 However, chlorine gas is toxic and corrosive, and
therefore a chlorine-free synthetic method is desirable.
Several chlorine-free syntheses of
1,2-benzisothiazolin-3-ones have been reported over the past decade: reaction of ammonia with
3H-1,2-benzodithiol-3-one or 3H-1,2-benzodithiol-3-one 1-oxide,5 reaction of thiosalicylic acid with
azide compounds,6 and cyclization of a thiosalicylhydroxamic acid.7 We developed a convenient
method for the synthesis of 1,2-benzisothiazolin-3-ones from 2-sulfenamoylbenzoates prepared by the
reaction of thiosalicylates with hydroxylamine-O-sulfonic acid (HOSA).8 In the course of that study, we

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HETEROCYCLES, Vol. 60, No. 8, 2003
found that transamination of 2-sulfenamoylbenzoates with 1,2-benzisothiazolin-3-one occurred at the
sulfur atom of the sulfenamide in the 2-sulfenamoylbenzoate.9 Transamination of bivalent sulfur
compounds has been reported in a few cases.10 Although the reactions of 2-sulfenamoylbenzothiazole
with amines were intensively investigated to develop vulcanizing agents,11 reactions of other
sulfenamides have scarcely been reported.10,12 Here we investigate reactions of N-unsubstituted
2-sulfenamoylbenzoates with various amines in an effort to develop a chlorine gas–free synthetic method
for
preparing
N-substituted
2-sulfenamoylbenzoates,
which
can
be
cyclized
to
1,2-benzisothiazolin-3-ones.4,13
RESULTS AND DISCUSSION
The transamination of sulfenamides sometimes requires heating to high temperature without solvent.12
In a previous paper, we reported that transamination of 2-sulfenamoylbenzoates (1) with
1,2-benzisothiazolin-3-one
(3a)
proceeded
in
toluene
at
100
°C
to
afford
2-(2-alkoxycarbonylphenylsulfenyl)-1,2-benzisothiazolin-3-ones (4).9 Using these reaction conditions,
we carried out the reactions of methyl 2-sulfenamoylbenzoate (1a) with various amines (Table 1).
When 1a was treated with aniline in toluene at 100 °C for 8 h, methyl N-phenyl-2-sulfenamoylbenzoate
(2a) was obtained in 48% yield (Entry 1). It seemed that the amine exchange reaction occurred on the
sulfur atom of 1a.
However, 1,2-benzisothiazolin-3-one (3a) was also a main product of the reaction
Table 1. Reaction of 1a with amines
O
S
O
O
Toluene
100 °C
OMe
S NHR1
2a-d
N R1
OMe
+
R1NH2
or
S NH2
3b-e
1a
Entry
R1
Ph
Product
2a
Yield (%)
1
2
3
4
5
6
7
48
51
54
62
61
68
57
31
p-MeC6H4
p-MeOC6H4
PhCH2
2b
2c
3b
p-MeOC6H4CH2
p-ClC6H4CH2
HO(CH2)3
t-Bu
3c
3d
3e
a
8
2d
a
In a sealed tube.

HETEROCYCLES, Vol. 60, No. 8, 2003
1857
O
OMe
(path a)
PhNH2
- NH3
OMe
S NHPh
2a
O
O
O
S NH2
1a
PhNH2
OMe
1a
(path b)
2a + 3a
- MeOH
O
NH
- NH3
S
3a
S
4a
N
S
Scheme 1.
(49% yield). Because 3a was formed by heating 1a under these reaction conditions,8 transamination
also occurred on 1a with 3a, and 2-(2-methoxycarbonylphenylsulfenyl)-1,2-benzisothiazolin-3-one (4a)
was formed. The reactivity of 4a was high toward amines, and 4a reacted with aniline to afford 2a and
3a13 (Scheme 1). Since almost equivalent amounts of 2a and 3a were isolated, it is plausible that 2a was
formed via path b. Once 3a was formed, the nucleophilicity of aniline decreased because 2a is an acidic
compound. For more basic anilines with higher nucleophilicities, direct transamination (path a) could
occur, and the yield of N-substituted sulfenamides improved (Entries 2 and 3). In reactions with
aliphatic amines, N-substituted sulfenamides (2) were not isolated, and cyclized N-substituted
1,2-benzisothiazolin-3-ones (3) were obtained (Entries 4–7). However, tert-butylamine provided only
N-substituted sulfenamide (2d) because cyclization was difficult owing to steric hindrance (Entry 8).
To prevent formation of 1,2-benzisothiazolin-3-one (3a), ethyl 2-sulfenamoylbenzoate (1b) was used
as a starting material (Table 2). Benzoate (1b) did not give 1,2-benzisothiazolin-3-one (3a) on heating at
100 °C in toluene.9 Thus, N-substituted sulfenamides were obtained in better yields with 1b than with
methyl ester (1a) (Entries 1–3). However, in reactions with benzylamines, cyclization to N-substituted
1,2-benzisothiazolin-3-ones was prohibited, and the products were a mixture of N-substituted
sulfenamides and 1,2-benzisothiazolin-3-ones (Entries 5–7). Although the N-substituted sulfenamides
obtained by transamination with aromatic amines such as 2a, 2b, 2c, 2e, 2f, and 2g could be easily
converted to N-substituted 1,2-benzisothiazolin-3-ones (3) in the presence of strong base,4,13
2-sulfenamoylbenzoates with bulky substituents on the nitrogen atom such as tert-butyl (2l) and
2-phenyl-2-propyl (2m) did not cyclize to 1,2-benzisothiazolin-3-ones under the same reaction conditions.
N,N-Disubstituted 2-sulfenamoylbenzoates (2n–p) were synthesized when secondary amines were used
(Entries 11–13).
Next, we investigated intramolecular transamination of 2-sulfenamoylbenzamide derivatives.
Because cyclization of 2-carbamoylbenzenesulfenyl halides has been reported,14 we expected that
2-sulfenamoylbenzamide derivatives would undergo intramolecular transamination. When we treated

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HETEROCYCLES, Vol. 60, No. 8, 2003
N - ( p - me t h y l p h e n y l ) t h i o s a l i c y l a mi d e w i t h HOS A t o s y n t h e s i z e s u l f e na mi d e ,
2-(p-methylphenyl)-1,2-benzisothiazolin-3-one (3g) was isolated as the main product. This result means
that once the sulfur atom was aminated, intramolecular transamination proceeded to form
1,2-benzisothiazolin-3-ones (3). Simultaneously, 2,2'-bis[N-(p-methylphenyl)carbamoylphenyl]
disulfide, formed by attack of the sulfur atom of the sulfenamide intermediate by the thiolate anion
(Scheme 2), was isolated as a by-product. The same aminations were carried out for various
thiosalicylamides (5) (Table 3). 1,2-Benzisothiazolin-3-ones (3) were obtained and the corresponding
sulfenamides were not detected during the reactions. N-tert-Butyl- (3j) and
N-(2-phenyl-2-propyl)-1,2-benzisothiazolin-3-ones (3k), which could not be synthesized by cyclization of
the corresponding sulfenamoylbenzoates (1), were obtained in these aminations. When the
thiosalicylamide (5) did not readily dissolve in alkaline solution, a mixture of methanol and water was
used as a solvent. N-Chloro-4-methylbenzenesulfonamide sodium salt (Chloramine-T) was also used as
Table 2. Reaction of 1b with amines
O
O
O
Toluene
100 °C
OEt
OEt
S NR1R2
2e-p
R1R2NH
N R1
+
and / or
S
S NH2
1b
3b-e
(R2 = H)
Entry
R1
Ph
R2 Time (h)
Products (% yield)
2e (71)
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
Et
8
4
8
8
4
6
6
4
4
6
4
4
4
p-MeC6H4
p-MeOC6H4
2-Pyridyl
PhCH2
2f (71)
2g (61)
2h (36)
2i (33), 3b (43)
2j (21), 3c (53)
2k (45), 3d (39)
3e (71)
p-MeOC6H4CH2
p-ClC6H4CH2
HO(CH2)3
t-Bu
a
9
2l (55)
2m (67)
2n (41)
2o (51)
10
PhMe2C
a
11
12
Et
a
–(CH2)4–
13
In a sealed tube.
–(CH2)2–O–(CH2)2–
2p (76)
a

HETEROCYCLES, Vol. 60, No. 8, 2003
1859
O
O
O
S
NHR1
NHR1
KOH
N R1
+
HOSA
- NH3
SH
S NH2
5
3
- NH3
NHR1
O
O
S
NHR1
S
)
2
Scheme 2.
an aminating agent, and 1,2-benzisothiazolin-3-ones were prepared (Entries 10–12).
In summary, the amino groups on the sulfenamides were easily displaced with amines by heating in
toluene to afford N-substituted 2-sulfenamoylbenzoates, N-substituted 1,2-benzisothiazolin-3-ones, or
both. Intramolecular transamination proceeded smoothly for 2-sulfenamoylbenzamide derivatives.
N-Unsubstituted sulfenamides behaved like sulfenyl halides, and new nitrogen–sulfur bonds were formed
in good yields.
a
Table 3. Cyclization of thiosalicylamides (5)
O
S
O
Aminating
Agent
NHR1
N R1
SH
5
3
Entry
R1
Aminating
Agent
HOSA
HOSA
HOSA
HOSA
HOSA
HOSA
HOSA
HOSA
HOSA
Chloramine-T
Chloramine-T
Chloramine-T
H2O MeOH
Time
(h)
3
0.5
1
3
0.5
3
3
3
Temp
(°C)
Product
Yield
(%)
41
60
44
40
79
52
67
88
52
87
35
(mL)
10
10
10
10
10
10
10
10
10
10
10
10
(mL)
10
–
10
10
–
10
10
10
10
10
10
10
1
2
3
4
5
6
7
8
9
Ph
p-MeC6H4
PhCH2
PhCH2CH2
HO(CH2)3
Cyclopropyl
t-Bu
PhMe2C
H
p-MeC6H4
t-Bu
0
0
0
0
0
0
0
0
3f
3g
3b
3h
3e
3i
3j
3k
3a
3g
3j
3
4
5
4
0
10
11
12
rt
rt
rt
PhMe2C
3k
74
a
1 mmol of thiosalicylamide (5) was used.

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HETEROCYCLES, Vol. 60, No. 8, 2003
EXPERIMENTAL
Melting points were determined on a Mettler FP90 microscope plate and are uncorrected. 1H NMR
spectra were obtained with a JEOL LA-500 spectrometer (500 MHz), and chemical shifts are reported in
ppm relative to internal tetramethylsilane. IR spectra were recorded on a JASCO FTIR-5300
spectrophotometer. Sulfenamides (1) were prepared by the method described in a previous paper.8
General procedure for the reaction of sulfenamide (1) with amines
A mixture of 2-sulfenamoylbenzoate (1, 1 mmol) and amine (1.2 mmol) was dissolved in toluene (10 mL),
and the solution was heated at 100 °C. After evaporation of toluene, the residual crude product was
chromatographed on silica gel. The structures of the products (2a–d, 2f, and 3b–e) were identified with
the data of our previous paper.13
Ethyl N-phenyl-2-sulfenamoylbenzoate (2e). Chromatographed with dichloromethane as an eluent;
mp 116-117 °C (ethanol); 1H NMR (CDCl3) δ 1.43 (3H, t, J = 7.1 Hz), 4.43 (2H, q, J = 7.1 Hz), 5.07 (1H,
br s), 6.87 (1H, ddd, J = 8.1, 7.1, 1.1 Hz), 6.97-7.01 (2H, m), 7.14-7.24 (3H, m), 7.40 (1H, ddd, J = 8.0,
7.1, 1.2 Hz), 7.50 (1H, dd, J = 8.0, 1.1 Hz), 8.06 (1H, dd, J = 8.1, 1.2 Hz); IR (KBr) νmax 3358, 1688,
1599, 1271, 1142, 748, 693 cm-1. Anal. Calcd for C15H15NO2S: C, 65.91; H, 5.53; N, 5.12. Found: C,
65.89; H, 5.48; N, 5.03.
Ethyl N-(p-methoxyphenyl)-2-sulfenamoylbenzoate (2g). Chromatographed with dichloromethane as
1
an eluent; mp 98-99.5 °C (dichloromethane-hexane); H NMR (CDCl3) δ 1.42 (3H, t, J = 7.1 Hz), 3.74
(3H, s), 4.42 (2H, q, J = 7.1 Hz), 4.92 (1H, br s), 6.78 (2H, d, J = 9.0 Hz), 6.91 (2H, d, J = 9.0 Hz), 7.16
(1H, ddd, J = 8.2, 7.7, 1.1 Hz), 7.40 (1H, td, J = 7.7, 1.4 Hz), 7.51 (1H, dd, J = 8.2, 1.1 Hz), 8.05 (1H, dd,
J = 7.7, 1.4 Hz); IR (KBr) νmax 3360, 1688, 1510, 1271, 1240, 825, 748 cm-1. Anal. Calcd for
C16H17NO3S: C, 63.34; H, 5.65; N, 4.62. Found: C, 63.15; H, 5.63; N, 4.53.
Ethyl
N-(2-pyridyl)-2-sulfenamoylbenzoate
(2h).
Chromatographed
with
dichloromethane-acetone-methanol (100 : 5 : 1) mixture as an eluent; mp 121.5-122.5 °C
1
(dichloromethane-hexane); H NMR (CDCl3) δ 1.43 (3H, t, J = 7.1 Hz), 4.44 (2H, q, J = 7.1 Hz), 6.77
(1H, ddd, J = 7.1, 5.1, 0.8 Hz), 7.01 (1H, dt, J = 8.4, 0.8 Hz), 7.18 (1H, ddd, J = 8.5, 7.5, 1.4 Hz),
7.39-7.52 (3H, m), 8.07 (1H, dd, J = 7.8, 1.4 Hz), 8.17 (1H, ddd, J = 5.0, 1.7, 0.8 Hz); IR (KBr) νmax 3133,
2976, 2890, 1699, 1601, 1439, 1271, 1144, 920, 748 cm-1. Anal. Calcd for C14H14N2O2S: C, 61.29; H,
5.14; N, 10.21. Found: C, 61.41; H, 5.07; N, 10.11.
Ethyl N-benzyl-2-sulfenamoylbenzoate (2i). Chromatographed with dichloromethane as an eluent;
1
Oil; H NMR (CDCl3) δ 1.39 (3H, t, J = 7.1 Hz), 2.87 (1H, br t, J = 5.8 Hz), 4.12 (2H, d, J = 5.8 Hz),
4.37 (2H, q, J = 7.1 Hz), 7.16 (1H, ddd, J = 8.2, 7.2, 1.1 Hz), 7.29-7.42 (5H, m), 7.54 (1H, ddd, J = 8.2,

HETEROCYCLES, Vol. 60, No. 8, 2003
1861
7.2, 1.5 Hz), 7.89 (1H, dd, J = 8.2, 1.1 Hz), 8.03 (1H, dd, J = 7.8, 1.5 Hz); IR (KBr) νmax 3339, 1701,
1456, 1271, 1269, 1101, 1055, 745 cm-1; HRMS Calcd for C16H17NO2S: 287.0980. Found: 287.0994.
Ethyl N-(4-methoxybenzyl)-2-sulfenamoylbenzoate (2j). Chromatographed with dichloromethane as
1
an eluent; mp 91.5-93.5 °C (ethanol-hexane); H NMR (CDCl3) δ 1.39 (3H, t, J = 7.1 Hz), 2.80 (1H,
br t, J = 5.8 Hz), 3.81 (3H, s), 4.05 (2H, d, J = 5.8 Hz), 4.38 (2H, q, J = 7.1 Hz), 6.89 (2H, dt, J = 8.8, 2.2
Hz), 7.16 (1H, ddd, J = 7.8, 7.6, 1.1 Hz), 7.32 (2H, dt, J = 8.8, 2.2 Hz), 7.54 (1H, ddd, J = 8.0, 7.4, 1.6
Hz), 7.88 (1H, dd, J = 8.2, 1.1 Hz), 8.04 (1H, dd, J = 7.8, 1.6 Hz); IR (KBr) νmax 3308, 1686, 1510, 1269,
1248, 1030, 747 cm-1. Anal. Calcd for C17H19NO3S: C, 64.33; H, 6.03; N, 4.41. Found: C, 64.30; H,
5.98; N, 4.20.
Ethyl N-(4-chlorobenzyl)-2-sulfenamoylbenzoate (2k). Chromatographed with dichloromethane as an
eluent; mp 59.0-61.5 °C (EtOH); 1H NMR (CDCl3) δ 1.39 (3H, t, J = 7.1 Hz), 2.91 (1H, br t, J = 5.8 Hz),
4.10 (2H, d, J = 5.8 Hz), 4.38 (2H, q, J = 7.1 Hz), 7.17 (1H, ddd, J = 7.8, 6.9, 1.0 Hz), 7.32 (4H, s), 7.54
(1H, ddd, J = 8.2, 6.9, 1.4 Hz), 7.84 (1H, dd, J = 8.2, 1.0 Hz), 8.04 (1H, dd, J = 7.8, 1.4 Hz); IR (KBr)
νmax 3326, 1701, 1271, 1254, 1101, 1059, 745 cm-1. Anal. Calcd for C16H16NO2S: C, 59.71; H, 5.01; N,
4.35. Found: C, 59.72; H, 4.96; N, 4.21.
Ethyl N-(t-butyl)-2-sulfenamoylbenzoate (2l). Chromatographed with dichloromethane-hexane (2 : 1)
mixture as an eluent; mp 71.5-72.5 °C (dichloromethane-hexane); 1H NMR (CDCl3) δ 1.22 (9H, s), 1.40
(3H, t, J = 7.1 Hz), 2.54 (1H, br s), 4.38 (2H, q, J = 7.1 Hz), 7.10 (1H, ddd, J = 7.8, 7.2, 1.2 Hz), 7.49 (1H,
ddd, J = 8.4, 7.7, 1.5 Hz), 7.99 (1H, dd, J = 7.8, 1.5 Hz), 8.16 (1H, dd, J = 8.4, 1.2 Hz); IR (KBr) νmax
3297, 2961, 1694, 1456, 1308, 1265, 1148, 748 cm-1. Anal. Calcd for C13H19NO2S: C, 61.63; H, 7.56; N,
5.53. Found: C, 61.92; H, 7.59; N, 5.44.
Ethyl
N-(2-phenyl-2-propyl)-2-sulfenamoylbenzoate
(2m).
Chromatographed
with
dichloromethane-hexane (2 : 1) mixture as an eluent; mp 87.5-88 °C (ethanol-hexane); 1H NMR (CDCl3)
δ 1.37 (3H, t, J = 7.1 Hz), 1.57 (6H, s), 3.06 (1H, br s), 4.36 (2H, q, J = 7.1Hz), 7.17 (1H, ddd, J = 8.2,
7.7, 1.1 Hz), 7.23-7.39 (3H, m), 7.50-7.57 (3H, m), 7.99 (1H, dd, J = 8.0, 1.1 Hz), 8.26 (1H, dd, J = 8.2,
1.1 Hz); IR (KBr) νmax 3299, 2976, 1686, 1456, 1267, 1100, 747 cm-1. Anal. Calcd for C18H21NO2S: C,
68.54; H, 6.71; N, 4.44. Found: C, 68.68; H, 6.71; N, 4.35.
Ethyl N,N-diethyl-2-sulfenamoylbenzoate (2n). Chromatographed with dichloromethane-hexane (1 :
1) mixture as an eluent; bp 163 °C (0.01 kPa); 1H NMR (CDCl3) δ 1.16 (6H, t, J = 7.1 Hz), 1.39 (3H, t, J
= 7.1 Hz), 3.07 (4H, q, J = 7.1 Hz), 4.38 (2H, q, J = 7.1 Hz), 7.11 (1H, ddd, J = 8.0, 7.1, 1.1 Hz), 7.48
(1H, ddd, J = 8.2, 7.1 1.4 Hz), 7.93 (1H, dd, J = 8.2, 1.1 Hz), 8.01 (1H, dd, J = 8.0, 1.4 Hz); IR (KBr)
νmax 1705, 1456, 1267, 1100, 1053, 745 cm-1. Anal. Calcd for C13H19NO2S: C, 61.63; H, 7.56; N, 5.53.
Found: C, 61.69; H, 7.77; N, 5.44.

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HETEROCYCLES, Vol. 60, No. 8, 2003
Ethyl S-pyrrolidino-2-thiobenzoate (2o). Chromatographed with dichloromethane-hexane (2 : 1)
1
mixture as an eluent; mp 57.5-59 °C (pentane); H NMR (CDCl3) δ 1.40 (3H, t, J = 7.0 Hz), 1.93-1.96
(4H, m), 3.20 (4H, br s), 4.37 (2H, q, J = 7.0 Hz), 7.12 (1H, td, J = 7.9, 0.9 Hz), 7.49 (1H, ddd, J = 8.2,
7.4, 1.2 Hz), 7.71 (1H, dd, J = 8.2, 0.9 Hz), 8.02 (1H, dd, J = 7.9, 1.2 Hz); IR (KBr) νmax 1692, 1271,
1103, 1053, 748 cm-1. Anal. Calcd for C13H17NO2S : C, 62.12; H, 6.82; N, 5.57. Found: C, 62.42; H,
6.84; N, 5.50.
Ethyl S-morpholino-2-thiobenzoate (2p). Chromatographed with dichloromethane as an eluent; mp
1
105.5-107 °C (benzene-hexane); H NMR (CDCl3) δ 1.41 (3H, t, J = 7.0 Hz), 3.07 (4H, t, J = 4.8 Hz),
3.82 (4H, t, J = 4.8 Hz), 4.37 (2H, q, J = 7.0 Hz), 7.16 (1H, td, J = 7.3, 1.2 Hz), 7.54 (1H, ddd, J = 8.5,
7.3, 1.5 Hz), 8.02-8.05 (2H, m); IR (KBr) νmax 1690, 1454, 1368, 1302, 1269, 1119, 922, 752 cm-1.
Anal. Calcd for C13H17NO3S : C, 58.40; H, 6.41; N, 5.24. Found: C, 58.68; H, 6.43; N, 5.11.
General procedure for the reaction of thiosalicylamide (5) with hydroxylamine-O-sulfonic acid
(HOSA)
The thiosalicylamide (5, 1 mmol) was dissolved in a solution of potassium hydroxide (67 mg, 1.2 mmol)
in water (10 mL) or, when the thiosalicylamide did not readily dissolve in alkaline solution, in a methanol
(10 mL)–water (10 mL) mixture. HOSA (170 mg, 1.5 mmol) in a solution of potassium hydroxide (112
mg, 2 mmol) in water (10 mL) was added dropwise to the thiosalicylamide solution at 0 °C (ice bath)
under a nitrogen atmosphere. The product was extracted three times with dichloromethane (20 mL each
time), and the organic layer was dried over magnesium sulfate. After the solvent was evaporated, the
crude product was chromatographed on silica gel. The structures of the products (3a, 3b, 3e, 3f, 3g, and
3i) were identified with the data of our previous papers.8,13
2-(2-Phenylethyl)-1,2-benzisothiazolin-3-one (3h). Chromatographed with ethyl acetate-hexane (1 : 1)
mixture as an eluent; mp 92.5-93.5 °C (hexane) (lit.,5 95-96 °C); 1H NMR (CDCl3) δ 3.07 (2H, t, J = 7.5
Hz), 4.13 (2H, t, J = 7.5 Hz), 7.22-7.26 (3H, m), 7.29-7.32 (2H, m), 7.39 (1H, ddd, J = 7.9, 7.6, 0.9 Hz),
7.51 (1H, d, J = 8.2 Hz), 7.59 (1H, ddd, J = 8.2, 7.6, 1.2 Hz), 8.03 (1H, d, J = 7.9 Hz); IR (KBr) νmax 1645,
1449, 1341, 1252, 1184, 735 cm-1.
2-t-Butyl-1,2-benzisothiazolin-3-one (3j). Chromatographed with dichloromethane-acetone-methanol
(100 : 5 : 1) mixture as an eluent; oil (lit.,15 mp 57-58 °C); 1H NMR (CDCl3) δ 1.71 (9H, s), 7.37(1H, ddd,
J = 8.0, 6.9, 1.1 Hz), 7.50 (1H, ddd, J = 8.0, 1.1, 0.8 Hz), 7.57 (1H, ddd, J = 8.0, 6.9, 1.3 Hz), 7.97 (1H,
ddd, J = 8.0, 1.3, 0.8 Hz); IR (KBr) νmax 1651, 1451, 1302, 1206, 741, 675 cm-1.
2-(2-Phenyl-2-propyl)-1,2-benzisothiazolin-3-one (3k). Chromatographed with dichloromethane as an
eluent; mp 131-132 °C (ethyl acetate-hexane); 1H NMR (CDCl3) δ 2.06 (6H, s), 7.29-7.43 (6H, m), 7.48

HETEROCYCLES, Vol. 60, No. 8, 2003
1863
(1H, ddd, J = 8.0, 1.1, 0.8 Hz), 7.58 (1H, ddd, J = 8.0, 7.1, 1.1 Hz), 7.92 (1H, ddd, J = 8.0, 1.3, 0.8 Hz);
IR (KBr) νmax 1638, 1445, 1327, 1179, 745, 698 cm-1. Anal. Calcd for C16H15NOS: C, 71.34; H, 5.61;
N, 5.20. Found: C, 71.38; H, 5.59; N, 5.12.
General
procedure
for
the
reaction
of
thiosalicylamide
(5)
with
N-chloro-4-methylbenzenesulfonamide sodium salt (Chloramine-T).
The thiosalicylamide (5, 1 mmol) was dissolved in a solution of potassium hydroxide (67 mg, 1.2 mmol)
in a methanol (10 mL)–water (10 mL) mixture. Chloramine-T trihydrate (423 mg, 1.5 mmol) in water
(10 mL) was added dropwise to the thiosalicylamide solution at rt under a nitrogen
atmosphere. The product was extracted three times with dichloromethane (20 mL each time), and the
organic layer was dried over magnesium sulfate. After the solvent was evaporated, the crude product
was chromatographed on silica gel.
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