JP2000007667A - Production of 1,2-benzoisothiazol-3-one compounds - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing a 1,2-benzoisothiazol-3-one compound, capable of simply, profitably and easily producing the 1,2- benzoisothiazol-3-one compound in mild conditions in a short process without using a substance highly dangerous on handling by subjecting a hydroxamic acid having a specific structure to a ring-closing reaction in the presence of a basic catalyst. SOLUTION: This method for producing a 1,2-benzoisothiazol-3-one compound of formula II (preferably 1,2-benzoisothiazol-3-one) comprises subjecting a hydroxamic acid of formula I (R1 is H, a halogen or the like) in the presence of a basic catalyst (preferably sodium hydroxide, potassium hydroxide) to a ring-closing reaction. The basic catalyst is preferably used in an amount of 1.1-5 fold equivalents that of the compound of formula I. The reaction solvent is preferably a polar solvent such as water. The reaction is preferably carried out in an inert gas at 0-100 deg.C. The compound of formula I is preferably obtained by reacting a 2-thiosalicylic acid derivative of formula III (X is a halogen, a 1-18C alkoxy or the like) with hydroxylamine.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a novel process for producing 1,2-benzisothiazol-3-ones. These 1,2-benzisothiazol-3-ones are useful compounds as antibacterial agents and antifungal agents.

[0002]

BACKGROUND OF THE INVENTION Conventionally, 1,2-benzoisothiazole-
As a method for producing 3-ones, a method of performing amidation or the like from 2- (methylthio) benzoyl chloride (Bu
II. Chem. Soc. Jpn. 55, 1183-7, 1982), cyclization from thiosalicylic acid through several steps and finally using a strong base, halogenating agent and the like [Org. Prep. Proced. i
nt.15 (5), 315-19, 1983, Ger. Offen. (198
6) No. 3500577], a method of cyclizing 2- (alkylthio) benzamides using a halogenating agent (Japanese Patent Laid-Open No. 7-196638).
JP-A-8-73448), a method of reacting 2- (alkylthio) benzaldehydes with hydroxylamine and cyclizing with a halogenating agent via oximes (JP-A-8-73448)
), And a method of cyclizing 2- (alkylthio) benzonitrile using a halogenating agent (JP-A-8-134051).

[0003] However, these production methods involve a large number of reaction steps or use highly hazardous reagents such as halogens and halogenating agents, which are not industrially satisfactory.

[0004]

DISCLOSURE OF THE INVENTION The present invention provides a simple and easy process in a short process, without using any industrially advantageous substance having a high risk for handling, and easily under a mild condition. It is to provide a method for producing thiazol-3-ones.

[0005]

Means for Solving the Problems As a result of intensive studies, the present inventors have found that a 2-thiosalicylic acid derivative represented by the general formula (3) is reacted with hydroxylamine in the presence of a basic catalyst to remove the compound. X, which is a leaving group, is eliminated to form 2-thiosalicylhydroxamic acid represented by the general formula (2), which is a reaction intermediate (hereinafter, referred to as “substitution reaction”). ) Was obtained (hereinafter referred to as “ring closure reaction”), and the present invention was completed based on such findings.

That is, the present invention provides a compound represented by the general formula (1)

[0007] [Wherein, R ¹ is a hydrogen atom, a halogen atom, a carbon number of 1 to 1
8 represents an alkyl group, an alkoxy group having 1 to 18 carbon atoms or a nitro group. When producing 1,2-benzisothiazol-3-ones represented by the general formula (2):

[0008] [Wherein, R ¹ is the same as R ¹ in formula (1). Wherein the hydroxamic acids represented by the formula [1] are subjected to a ring closure reaction in the presence of a basic catalyst.

Further, the present invention provides a compound of the general formula (3)

[0010][Wherein, R¹Is R in the general formula (1)¹Same as
You. X is a halogen atom, an alkoxy having 1 to 18 carbon atoms
Group, cycloalkyloxy group having 5 to 7 carbon atoms, 7 carbon atoms
To 20 aralkyloxy groups or groups —N (R²)
(R³). R², R ³Are the same or different
And represents an alkyl group having 1 to 18 carbon atoms. ]
A 2-thiosalicylic acid derivative and hydroxylamine
Represented by the general formula (2) obtained by the reaction (substitution reaction)
Hydroxamic acids are subjected to a ring closure reaction to give 1,2-
A method for producing benzoisothiazol-3-ones is also provided.
provide.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION R ^{1 of} 1,2-benzisothiazol-3-one represented by the general formula (1) according to the present invention
As a hydrogen atom, a chlorine atom, a bromine atom, a methyl group,
Ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, t-butyl group, sec-butyl group, n-hexyl group, n-octyl group and other alkyl groups, methoxy group, ethoxy group, propoxy group And alkoxy groups such as butoxy group, nitro group and the like. The substitution position is not particularly limited.

Specific compounds of the 1,2-benzisothiazol-3-one represented by the general formula (1) include:
1,2-benzisothiazol-3-one, 4-methyl-1,2-benzisothiazol-3-one, 5-methyl-1,2-benzisothiazol-3-one, 6-methyl-1, 2-benzoisothiazol-3-one, 7-
Methyl-1,2-benzisothiazol-3-one, 4
-Ethyl-1,2-benzisothiazol-3-one,
5-ethyl-1,2-benzisothiazol-3-one, 6-ethyl-1,2-benzisothiazol-3-
On, 7-ethyl-1,2-benzisothiazole-3
-One, 4-propyl-1,2-benzisothiazol-3-one, 5-propyl-1,2-benzisothiazol-3-one, 6-propyl-1,2-benzisothiazol-3-one 7-propyl-1,2-benzisothiazol-3-one, 4-butyl-1,2-benzisothiazol-3-one, 5-butyl-1,2-benzisothiazol-3-one, 6 -Butyl-1,2-benzisothiazol-3-one, 7-butyl-1,2-
Benzoisothiazol-3-one, 4-methoxy-1,
2-benzoisothiazol-3-one, 5-methoxy-
1,2-benzisothiazol-3-one, 6-methoxy-1,2-benzisothiazol-3-one, 7-methoxy-1,2-benzisothiazol-3-one,
-Nitro-1,2-benzisothiazol-3-one,
5-nitro-1,2-benzisothiazol-3-one, 6-nitro-1,2-benzisothiazol-3-one
On, 7-nitro-1,2-benzisothiazole-3
-One, 4-chloro-1,2-benzisothiazole-
3-one, 5-chloro-1,2-benzisothiazol-3-one, 6-chloro-1,2-benzisothiazol-3-one, 7-chloro-1,2-benzisothiazol-3-one And the like, and more preferred compounds are 1,2-benzisothiazol-3-one, 7-
Methyl-1,2-benzisothiazol-3-one, 5
-Butyl-1,2-benzisothiazol-3-one,
6-methoxy-1,2-benzisothiazol-3-one, 7-nitro-1,2-benzisothiazol-3-one
On, 6-chloro-1,2-benzisothiazole-3
-On and the like.

The hydroxy of the present invention represented by the general formula (2)
R of samic acids¹Is R of the general formula (1) ¹Is the same as

Specific examples of hydroxamic acids include 2-
Thiobenzohydroxamic acid, 3-methyl-2-thiobenzohydroxamic acid, 5-butyl-2-thiobenzohydroxamic acid, 4-methoxy-2-thiobenzohydroxamic acid, 3-nitro-2-thiobenzohydroxamic acid, 4 −
Chloro-2-thiobenzohydroxamic acid and the like are exemplified.

The basic catalyst used for the ring closure reaction includes
Sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, sodium methoxide, sodium ethoxide, potassium tert-butoxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium hydride , Metal sodium, metal potassium, ammonia and the like,
Preferably, sodium hydroxide and potassium hydroxide are used.

The amount of the basic catalyst is 1 to 10 equivalents, preferably 1.1 to 5 equivalents to 2-thiobenzohydroxamic acids.

The reaction solvent used for the ring closure reaction is not particularly limited as long as it is a solvent that is stable under basic conditions. Specifically, it may have an ether bond in the molecule or may be an aromatic solvent. 1-8 carbon atoms which may have a substituent
Alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, n-heptanol, isoamyl alcohol, n-hexanol, 2-ethylbutanol,
Diols such as octanol, benzyl alcohol, 2-methoxyethanol, 2-ethoxyethanol, ethylene glycol and propylene glycol, and hydrocarbons such as water, n-pentane, n-hexane, cyclohexane, methylcyclohexane, benzene, toluene and xylene ,
Examples thereof include hydrogen halides such as chlorobenzene and dichlorobenzene, dimethyl sulfoxide, sulfolane, and dimethylformamide. A single solvent or a mixture of two or more solvents may be used. Particularly preferred is
It is a polar solvent such as water, methanol and ethanol.

The amount of the reaction solvent used is 1 to 100 times, preferably 1 to 30 times the weight of 2-thiobenzohydroxamic acids.

The reaction temperature of the ring closure reaction is -20 to 1
The temperature is 50 ° C, preferably 0 to 100 ° C.

The reaction time of the ring closure reaction varies depending on the reaction conditions, but is usually 1 to 40 hours.

The reaction is carried out in air or in an inert gas such as nitrogen or argon, but is preferably carried out in an inert gas.

After the completion of the reaction, the reaction solution is subjected to a post-treatment by a conventionally known method such as liquid-liquid extraction and crystallization to obtain 1,2.
It is possible to obtain basic catalyst salts of -benzoisothiazol-3-ones.

On the other hand, the hydroxamic acids represented by the general formula (2) of the present invention are usually 2-hydroxy acids represented by the general formula (3).
It is obtained by a reaction (substitution reaction) between a thiosalicylic acid derivative and hydroxylamine.

According to the present invention, 2-
X in the thiosalicylic acid derivative is a group which is easily eliminated by a reaction with hydroxylamine, and as a 2-thiosalicylic acid derivative, 2-thiosalicylic acid halide,
Examples thereof include 2-thiosalicylic acid esters, 2-thiosalicylic acid alkylamides, 2-thiosalicylic anhydrides, and 2-thiosalicylic acid mixed anhydrides. Specific examples of the corresponding X include a halogen atom and an alkoxy having 1 to 18 carbon atoms. Group,
C5-C7 cycloalkyloxy group, C7-C2
0 aralkyloxy group, group —N (R ² ) (R ³ ) [R
² and R ³ are the same or different and each represent a hydrogen atom or a carbon atom of 1 to 1;
8 represents an alkyl group. And a group R ⁴ COO— (R ⁴ is an alkyl group having 1 to 18 carbon atoms).

More specific examples of X include halogen atoms such as chlorine and bromine, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, t- -Butoxy group, n-pentyloxy group, isoamyloxy group, n-hexyloxy group,
2-ethylhexyloxy group, alkoxy group such as n-octyloxy group, cycloalkyloxy group such as cyclopentyloxy group and cyclohexyloxy group, benzyloxy group, 1-phenylethyloxy group, 2-phenyloxy group, 1-phenyl Aralkyloxy groups such as propoxy group, 2-phenylpropoxy group, 3-phenylbenzyloxy group, ethylbenzyloxy group, amino group, methylamino group, ethylamino group, n-propylamino group, isopropylamino group, butylamino, etc. And dialkylamino groups such as a monoalkylamino group, a dimethylamino group, a diethylamino group, a dipropylamino group, a dibutylamino group, and a methylethylamino group.

Of the above X, a halogen atom, an alkoxy group having 1 to 18 carbon atoms, a cycloalkyloxy group having 5 to 7 carbon atoms, an aralkyloxy group having 7 to 20 carbon atoms or a group -NR ² R ³ is particularly preferable. , More preferably 1 carbon atom
An alkoxy group having 18 to 18 carbon atoms, a cycloalkyloxy group having 5 to 7 carbon atoms, or an aralkyloxy group having 7 to 20 carbon atoms.

Preferred specific 2-thiosalicylic acid derivatives represented by the general formula (3) include methyl 2-thiosalicylate, ethyl 2-thiosalicylate, n-propyl 2-thiosalicylate, isopropyl 2-thiosalicylate, 2
-N-butyl thiosalicylate, isobutyl 2-thiosalicylate, sec-butyl 2-thiosalicylate, t-butyl 2-thiosalicylate, n-pentyl 2-thiosalicylate, isoamyl 2-thiosalicylate, n-hexyl 2-thiosalicylate 2-ethylhexyl 2-thiosalicylate, n-octyl 2-thiosalicylate, cyclohexyl 2-thiosalicylate, benzyl 2-thiosalicylate, 2-thiosalicylic chloride, 2-thiosalicylic bromide, 2-thiosalicylic amide, 3-methyl And methyl 2-thiosalicylate, methyl 5-butyl-2-thiosalicylate, methyl 4-methoxy-2-thiosalicylate, methyl 3-nitro-2-thiosalicylate, and methyl 4-chloro-2-thiosalicylate.

The 2-thiosalicylic acid derivative represented by the general formula (3) can be obtained by any method.
-Easily obtained by subjecting thiosalicylic acid to acid halide, amidation and esterification in a conventional manner (Bull. C
hem.Soc.Jpn., 55,1183-7, (1982), J.Org.Chem., 40,202
9-31, (1975)).

Using a 2-thiosalicylic acid derivative represented by the general formula (3) as a raw material, a hydroxamic acid represented by the general formula (2) is obtained by a reaction (substitution reaction) with hydroxylamine, and further by a ring closing reaction. The method for producing 1,2-benzisothiazol-3-ones represented by the general formula (1) includes the following step (4):

[0030] Is represented by

For example, the leaving group X (X = OCH ₃ ) is eliminated by a substitution reaction between 2-thiosalicylic acid methyl ester and hydroxylamine to give an intermediate, 2-thiobenzohydroxamic acid. To form This hydroxamic acid easily forms 1,2-benzoisothiazol-3-one by a ring closure reaction in the presence of an alkali.

Therefore, the hydroxamic acids represented by the general formula (2) obtained by the substitution reaction can be isolated. Alternatively, the ring-closing reaction can be carried out without isolation to give the hydroxamic acid represented by the general formula (1). 1,2-benzisothiazole-3
-It is also possible to lead to ons. Considering that the hydroxamic acid represented by the general formula (2) easily becomes a target product by a ring closure reaction, 1,2-benzoisothiazol-3-one can be obtained by a ring closure reaction without isolating the hydroxamic acid. A method for obtaining the compounds (hereinafter, referred to as “substitution / ring closure reaction”) is preferred.

Hereinafter, hydroxylamine and a compound represented by the general formula (3)
Reaction with a 2-thiosalicylic acid derivative represented by the following formula (substitution reaction), and 1,2-benzoisothiazole-3 by ring closure reaction without isolating the hydroxamic acid obtained by the substitution reaction. The method for obtaining -ones (substitution / ring closure reaction) will be described.

As the hydroxylamine used for the substitution reaction or the substitution / ring-closure reaction, those commercially available as various salts such as hydrochloride, sulfuric acid and the like are usually used after desalting using a basic catalyst. Desalting may be performed in the reaction system,
Hydroxylamine desalted in advance may be added to the reaction system. In consideration of the stability of hydroxylamine and the easiness of the reaction, it is preferable that the hydroxylamine salt is desalted in the reaction system and then reacted with the 2-thiosalicylic acid derivative.

The hydroxylamine salt is desalted into free hydroxylamine (hereinafter referred to as "desalting reaction").
In this case, the same basic catalyst as that used in the ring closure reaction can be used.

The amount of hydroxylamine is 1 to 10 moles, preferably 1 to 5 moles relative to the 2-thiosalicylic acid derivative.

As the reaction solvent used in the substitution reaction, the same solvent as that used in the ring closure reaction can be used.

The amount of the reaction solvent used in the substitution reaction is 1 to 100 times, preferably 1 to 30 times the weight of the 2-thiosalicylic acid derivative.

The reaction temperature of the substitution reaction is from -20 to 1
The temperature is 50 ° C, preferably 0 to 100 ° C.

The reaction time of the substitution reaction varies depending on the reaction conditions, but is usually 1 to 40 hours.

The reaction is carried out in air or in an inert gas such as nitrogen or argon, but is preferably carried out in an inert gas.

After completion of the reaction, 2-thiobenzohydroxamic acids can be obtained by subjecting the reaction solution to post-treatment by a conventionally known method such as liquid-liquid extraction and crystallization.

The hydroxamic acids represented by the general formula (2) obtained by the above method are subjected to the above-mentioned ring-closing reaction to give the 1,2-benzoisothiazole-3 of the general formula (1).
-Can be turned on.

On the other hand, the amount of the base used in the substitution / ring-closure reaction performed without isolating the 2-thiobenzohydroxamic acids varies depending on the hydroxylamine salt used.
When desalting is required, the 2-thiosalicylic acid derivative is used in consideration of being used for desalting of hydroxylamine and salt formation of the resulting 1,2-benzoisothiazol-3-ones. It is 10 to 10 equivalents, preferably 2 to 5 equivalents.

As the reaction solvent used in the substitution / ring closure reaction, the same solvent as that used in the ring closure reaction can be used.

The amount of the reaction solvent used in the substitution / ring-closure reaction is 1 to 10 with respect to the 2-thiosalicylic acid derivative.
The weight is 0 times, preferably 1 to 30 times the weight.

The reaction temperature of the substitution / ring closure reaction is -2.
The temperature is 0 to 150 ° C, preferably 0 to 100 ° C.

The reaction time of the substitution / ring closure reaction varies depending on the reaction conditions, but is usually 1 to 40 hours.

The reaction is carried out in air or in an inert gas such as nitrogen or argon, but is preferably carried out in an inert gas.

After completion of the reaction, the reaction solution is subjected to a post-treatment by a conventionally known method such as liquid-liquid extraction and crystallization to obtain 1,2.
-Obtaining basic catalyst salts of benzoisothiazol-3-ones.

The 1,2-benzisothiazol-3-ones obtained by the ring closure reaction or the substitution / ring closure reaction are present as basic catalyst salts (for example, 1,2-benzisothiazol-3-one sodium salt). , 1,2-benzisothiazol-3-one potassium salt) and dilute hydrochloric acid to obtain the desired product.

The 1,2-benzisothiazol-3-ones thus obtained can be used in an unpurified state. Further, liquid-liquid extraction, solvent washing, recrystallization, chromatography It can also be used after purification by a known purification method.

[0053]

The present invention will be specifically described below with reference to examples. The analysis of 2-thiobenzohydroxamic acid and 1,2-benzisothiazol-3-one in Examples was carried out by HPLC using an ODS column [eluent: 10 mmol KH ₂ PO ₄ solution (PH = 3.0). / THF = 1/1 (v
ol / vol)] according to the internal standard method.

Column: Tosoh ODS-80Ts (4.6
mmφ × 15cm) Flow rate: 0.6ml / min Temperature: 40 ° C Detection: UV 236nm

Example 1 Synthesis of 2-thiobenzohydroxamic acid (substitution reaction) Under a nitrogen atmosphere, 20 ml of methanol was placed in a 100 ml two-necked flask.
1.26 g (0.03 mol) of sodium hydroxide and 1.04 g (0.015 mol) of hydroxylamine hydrochloride were added. Next, the mixture was cooled to room temperature, 1.68 g (0.01 mol) of methyl 2-thiosalicylate was added, and the mixture was stirred for 2 hours. Thereafter, methanol was distilled off, and the obtained solid was washed with water to remove inorganic salts. The remaining solid was recrystallized from a mixed solvent of water and ethanol to obtain sodium 2-thiobenzohydroxamate. The salt was neutralized with dilute hydrochloric acid under ice-cooling and 1.27 g of 2-thiobenzohydroxamic acid (75% yield). Rate).

IR: 2500-3500 cm ^-1 (O
H, NH), 1640 (C = O) HPLC analysis: retention time 3.4 minutes

Synthesis of 1,2-benzisothiazol-3-one (ring closure reaction) 2-thiobenzohydroxamic acid obtained by the above method.
27 g (8.4 mmol) was dissolved in 100 ml of methanol, 0.84 g (002 mol) of sodium hydroxide was added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 24 hours. The reaction solution was neutralized with dilute hydrochloric acid and analyzed by HPLC.
The conversion of 2-benzoisothiazol-3-one is 96.
2% (4.1 min retention time on HPLC).

Example 2 (Substitution and Ring Closure Reaction) Under a nitrogen atmosphere, 20 ml of methanol was placed in a 100 ml two-necked flask.
1.26 g (0.03 mol) of sodium hydroxide and 1.04 g (0.015 mol) of hydroxylamine hydrochloride were added and stirred. After cooling to room temperature, 1.82 g (0.01 mol) of ethyl 2-thiosalicylate was added, and the mixture was stirred. Two hours after the start of the reaction, a part of the reaction solution was collected, neutralized with dilute hydrochloric acid, and analyzed by HPLC. As a result, a peak of 2-thiobenzohydroxamic acid was recognized at a retention time of 3.4 minutes. After continuing the reaction for a further 24 hours, the reaction solution was neutralized with diluted hydrochloric acid and analyzed by HPLC.
The conversion of 1,2-benzisothiazol-3-one is 9
2.5%.

Examples 3 to 17 (Substitution and Ring Closure Reaction) The reaction was carried out in the same manner as in Example 2 except that ethyl 2-thiosalicylate was changed to the compound (0.01 mol) shown in Table 1. Table 1 shows the results.

[0060]

Examples 18 to 21 (Substitution and Ring Closure Reaction) The reaction was carried out in the same manner as in Example 2 except that methanol was changed to a solvent shown in Table 2. Table 2 shows the results.

[0062]

Examples 22 to 26 (Substitution and Ring Closure Reaction) The reaction was carried out in the same manner as in Example 2 except that ethyl 2-thiosalicylate was changed to the compound (0.01 mol) shown in Table 3. Table 3 shows the results.

[0064]

Example 27 (Substitution and Ring Closure Reaction) The reaction was carried out in the same manner as in Example 2 except that sodium hydroxide was changed to potassium hydroxide (2.64 g, 0.04 mol). As a result, the reaction rate was 91.8%.

[0066]

According to the present invention, 1,2-benzisothiazol-3-ones, which are useful as antibacterial agents and antifungal agents, can be mildly prepared in a shorter process than before and without using highly dangerous substances. It can be easily manufactured under various conditions.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Shigeo Miki 13 Fukumi-ku, Kyoto-shi, Kyoto, Japan

Claims (5)

[Claims] 1. General formula (1) [Wherein, R ¹ is a hydrogen atom, a halogen atom, a carbon number of 1 to 1
8 represents an alkyl group, an alkoxy group having 1 to 18 carbon atoms or a nitro group. When producing 1,2-benzisothiazol-3-ones represented by the general formula (2): [Wherein, R ¹ is the same as R ¹ in formula (1). Wherein the hydroxamic acids represented by the general formula (1) are subjected to a ring-closing reaction in the presence of a basic catalyst. 2. A method for producing 1,2-benzoisothiazol-3-ones represented by the general formula (1). 2. The 1,2-benzo represented by the general formula (1)
When producing isothiazol-3-ones, the general formula
(3)[Wherein, R¹Is R in the general formula (1)¹Same as
You. X is a halogen atom, an alkoxy having 1 to 18 carbon atoms
Group, cycloalkyloxy group having 5 to 7 carbon atoms, 7 carbon atoms
To 20 aralkyloxy groups or groups —N (R²)
(R³). R², R ³Are the same or different
And represents an alkyl group having 1 to 18 carbon atoms. ]
2-thiosalicylic acid derivative and hydroxylamine
Hydroxamic acid of the general formula (2) obtained accordingly
2. The compound according to claim 1, which undergoes a ring closure reaction.
Method for producing 1,2-benzisothiazol-3-ones
Law. 3. X is an alkoxy group having 1 to 18 carbon atoms,
Cycloalkyloxy group having 5 to 7 carbon atoms or 7 to 7 carbon atoms
3. The aralkyloxy group of claim 1, wherein
A method for producing 2-benzoisothiazol-3-ones. 4. The method for producing 1,2-benzoisothiazol-3-ones according to claim 1, wherein the basic catalyst is potassium hydroxide or sodium hydroxide. 5. The method for producing 1,2-benzisothiazol-3-ones according to claim 1, wherein R ¹ is a hydrogen atom.