1968
C. K. Jin et al.
LETTER
46193n. (c) Davis, M. Adv. Heterocycl. Chem. 1972, 14, 58.
(d) Butti, A.; Gazzani, G. Chem Abstr. 1977, 86, 145938x.
(e) Kamigata, N.; Hashimoto, S.; Kobatashi, M.; Nakanishi,
H. Bull. Chem. Soc. Jpn. 1985, 58, 3131. (f) Bryce, M. R.;
Dransfield, T. A.; Kandeel, K. A.; Vernon, J. M. J. Chem.
Soc., Perkin Trans. 1 1988, 2141. (g) Scurlock, R.; Rougee,
M.; Bensasson, R. V.; Evers, M.; Dereu, N. Phytochem.
Photobiol. 1991, 54, 733. (h) Daich, A.; Decroix, B. J.
Heterocycl. Chem. 1991, 28, 1881. (i) Wright, S. W.;
Petraitis, J. J.; Abelman, M. M.; Bostrom, L. L.; Corbett, R.
L.; Green, A. M.; Kindt, R. M.; Magolda, R. L. Bioorg. Med.
Chem. Lett. 1993, 3, 2875. (j) Kim, W.; Dannaldson, J.;
Gates, K. S. Tetrahedron Lett. 1996, 37, 5337. (k) Kagano,
H.; Goda, H.; Yoshida, K.; Yamamoto, M.; Sakaue, S. U. S.
Patent 5,633,384, 1997; and references cited therein.
(7) Procedure of 1,2-Benzisothiazolin-3(2H)-one (2).11
To a 1000 L reactor was equipped with a mechanical stirrer,
a thermometer, and a condenser, 28% NaOMe (52.1 kg) in
MeOH solution was added for 10 min and distilled under
reduced pressure (60 °C/750 mmHg, 2.5 h) to get the MeOH
(15 L). In order to get rid of the extra MeOH, toluene (100
kg) was added and distilled to get the MeOH (15 L) for 1.5
h. Acetamide (16 kg) was added and refluxed for 1 h, then,
the reactor was cooled to 25 °C. Dimethyl 2,2¢-
O
S
O
S
O
S
O
a
OH
2
OMe
2
b
N
CH3
Na
2
1
3
4
c
O
O
N
CH3
O
O
OH-
Na
O
O
S
S
N
CH3
Na
N
S
O
CH3
S
ONa
Na
N
7
6
H3C
O
O
5
O
O
NH
d
NNa
S
S
8
2
dithiodibenzoate (3) (23.5 kg) was slowly added at 25 °C,
the reaction mixture was refluxed at 80 °C for 2 h, cooled to
<20 °C, added H2O (150 L), stirred for 30 min, filtered, and
separated to give aqueous layer and toluene layer (70 kg).
The aqueous layer was added 28% H2O2 (12 kg) dropwisely
for 30 min (increasing temperature to 50–55 °C). The basic
active carbon (3 kg) and Al2O3 (DN-3) (300 g) were added,
stirred for 1 h at 25 °C, and filtered. Addition of conc. HCl
(20 kg, 35% solution, and pH = 3–4) was added dropwisely
to precipitate the wet 1,2-benzisothiazolin-3(2H)-one (2),
which was filtered, washed with cold water (30 L), and dried
on air to afford 2 (18 kg, 85%) as off-white solid (MeOH),
mp 157–158 °C (lit.12 mp 158–159 °C).
Scheme 2 Conditions: a) MeSO4, 5% NaOH, 25 °C, 3 h;
b) CH3CONH2, NaOMe, toluene, reflux, 3 h; c) 28% H2O2, 50 °C,
30 min; d) concd HCl, 25 °C.
that immediately undergoes cyclization giving 7, eventu-
ally affording the intermediate 8. The intermediate 8 was
acidified with concd HCl to give the compound 2 as off-
white solid (Scheme 2).
In conclusion, we found a simple and economical process
for producing 1,2-benzisothiazolin-3(2H)-one (2) on an
industrial scale, without using materials that are costly
and dangerous in handling.
IR (KBr): 3420, 3056, 2911, 1630 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.37 (s, 9 H), 5.70 (br s,
1 H), 6.53 (d, 1 H, J = 1.7 Hz), 7.37–7.62 (m, 5 H), 11.64
(br s, 1 H).
References
Anal. Calcd for C7H5NOS: C, 55.61; H, 3.33; N, 9.26; S,
21.21. Found: C, 55.45; H, 3.50; N, 9.52; S, 21.08.
(8) The purity of 2 was verified by HPLC analysis employing
the Shimadzu LC-6A instrument equipped with an SPD-6A
UV detector as follows: Compound 2: Detector, Youngjin M
720; pump, waters 510; integrator, waters 746, Youngjin D
520B; wave length, UV-225 nm, column, ODS-2 (250 nm ×
4.6Y); end time, 30 min; eluent MeOH–H2O (35:65, v/v);
flow rate, 1.0 mL/min; attenuation, 1.28; chart speed, 0.5.
Procedure is as follows: 10 mg standard 1,2-
(1) Dozen Tech Company, Ltd., 955-1 Dohwa, 402-060
Incheon, Republic of Korea.
(2) Mckibben, M.; McClelland, E. W. J. Chem. Soc. 1923, 123,
170.
(3) (a) Morley, J. S. British Patents, 848,130, 1960; Chem Abstr.
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1301. (e) Fisher, R.; Hurni, H. Arzneim.-Forsch. 1964, 14,
1306.
benzisothiazolin-3(2H)-one (BIT) (2) is weighed to 0.1 mg
accuracy in 100 mL flask and added 10 mL of 0.5 (w/v)%
methylbenzoate/MeOH. The flask is filled up with HPLC
eluent to 100 mL. Compound 2 is prepared as same as
standard BIT. At least three HPLC tests are conducted until
constant areas are obtained. Compound 2 assay is calculated
from the HPLC area in proportion to standard BIT.
Calculation was conducted as follows: Compound 2
assay = (the area of compound 2 ≥ the area of
(4) Neustadt, P. T.; Ludwigshafen, H. J. U. S. Patent, 4,736,040,
1988.
(5) (a) McClelland, E. W.; Gait, A. J. J. Chem. Soc. 1926, 921.
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J. P.; New, J. S.; Smith, D. W.; Lobeck, W. G.; Catt, J. D.;
Minielli, J. L.; Eison, M. S.; Taylor, D. P.; Riblet, L. A.;
Temple, D. L. J. Med. Chem. 1986, 29, 359. (d) Miura, Y.
J. Org. Chem. 1988, 53, 2850. (e) J.P. Patent Appl. No.
176752, 1998.. (f) Shimizu, M.; Kikumoto, H.; Konakahara,
T.; Gama, Y.; Shibuya, I. Heterocycles 1999, 51, 3005.
(g) Chiyoda, T.; Iida, K.; Takatori, K.; Kajiwara, M. Synlett
Lett. 2000, 1427. (h) J.P. Patent Appl. No. 266310, 2001.
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1968, 23, 1075. (b) Grivas, J. C. Chem. Abstr. 1972, 76,
methylbenzoate)/(the area of standard BIT ≥ the area of
methylbenzoate) × 100.
(9) Oae, M.; Doi, J. T. Organic Sulfur Chemistry: Structure and
Mechanism; CRC Press: Boca Raton, Ann Arbor, Boston,
London, 1991, 230.
(10) Neustadt, P. T.; Ludwigshafen, H. J. U. S. Patent 4,736,040,
1998.
(11) Nam, K. S.; Lee, W. S. KR Appl. No. 2001-43498, 2001.
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Synlett 2003, No. 13, 1967–1968 © Thieme Stuttgart · New York