JPS6025431B2 - Method for producing 2-benzothiazolinone compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION This invention provides a halonitrobenzene compound represented by the general formula (wherein R means hydrogen, halogen, alkyl group, trihalomethyl group, or alkoxy group, and X means halogen),
Metal polysulfide, metal sulfide, and then general formula X2-R2
(0) (In the formula, R2 means an esterified carboxyl group and X2 means an acid residue, respectively.) A 2-monosubstituted thioaniline compound represented by the following formula (in which R has the same meaning as before) is then subjected to a ring-opening reaction in the presence of an acid catalyst to form a 2-benzothia compound represented by the general formula (in which R has the same meaning as before). The present invention relates to a method for producing a 2-benzothiazolinone compound, which comprises obtaining a zolinone compound.

This invention provides a new method for producing a 2-benzothiazolinone compound (W).

As a secondary method for producing the 2-benzothiazolinone compound (W), [11] The corresponding chloronitrobenzene compound is reacted with sodium polysulfide and carbon disulfide.
-Production method by converting benzothiazole thiol into sodium 2-penzothiazole sulfonate by oxidizing it with potassium permanganate in alkaline conditions, and then heating it in acidic hydrochloric acid to desulfite (Pharmaceutical Journal No. 77) Vol. 4, No. 1, pp. 8-349), [21 Method for producing a corresponding halonitrobenzene compound by reacting sodium sulfide and then phosgene (Tsubaki Kosho No. 47-51347) and the corresponding bis(2-nitrobenzene compound). A method is known in which a phenyl disulfide compound is reacted with an alkali metal sulfide and then with phosgene. However, in the above-mentioned known method '1', it is necessary to use highly flammable and toxic carbon disulfide, and (b) a large amount of sulfur dioxide gas is generated in the desulfurization process. , In addition, both the known method ① and the leg require the use of toxic phosgene, etc.
None of the known methods is satisfactory as an industrial method because it is difficult to maintain work safety and protect the environment. The inventors conducted various studies to overcome these drawbacks, and as a result, they completed the method of the present invention, which does not have the above-mentioned drawbacks and can obtain the target compound (W) in high yield.

The reaction of this invention begins with a halonitrobenzene compound (1).
This is done by reacting a metal polysulfide to a polysulfide.

Halonitrobenzene compound (1) used in this reaction
In the definition, the halogen represented by R includes chlorine, bromine, iodine and fluorine, and the alkyl group includes, for example, methyl, ethyl, propyl, isopropyl,
Examples of the trihalomethyl group include trichloromethyl, tribromomethyl, dichlorobromomethyl, trifluoromethyl, etc., and examples of the alkoxy group include methoxy, ethoxy, propoxy, and isomethyl. Examples include propoxy, butoxy, benzyloxy, hexyloxy, etc., and examples of the halogen represented by X include the same as those mentioned above. In addition, as polysulfide metals used in this reaction, for example, alkali metal disulfides such as sodium disulfide and potassium disulfide are often used, but are not limited to these, and these may be used as necessary. It may also be made from a corresponding metal sulfide and sulfur. This reaction is carried out in a transparent solvent, and is often carried out in a mixed solvent of water and a water-soluble organic solvent such as acetone, but is not limited to this. Without,
Any solvent that does not adversely affect the reaction can be used.

This reaction is usually carried out under heating at about the boiling point of the solvent.

The reaction product thus obtained has the general formula (wherein R
, has the same meaning as before), and it is possible to react it with a metal sulfide after forming it alone, but for example, when compound (1) is reacted with a metal polysulfide, a hydrous organic solvent is used. When the reaction is carried out in a reactor, good results are often obtained by distilling off only the organic solvent from the reaction mixture and allowing the metal sulfide to act on it without isolating the compound.

As the metal sulfide used in this reaction, for example, alkali metal sulfides such as sodium sulfide and potassium sulfide are often used, but the metal sulfide is not limited to these.

This reaction is usually carried out in a solvent, and water is often used as the solvent, but the solvent is not limited thereto, and any solvent that does not adversely affect this reaction can be used.

This reaction may be carried out by adding a base such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, or the like. This reaction is usually carried out under heating at about the boiling point of the solvent.

The reaction product thus obtained has the general formula (wherein R
, has the same meaning as above) or its metal salt.Although it is possible to react with the dioxylic acid ester compound (0) after making it into a single unit, it is also possible to react with the reaction solution without isolation. Good results are often obtained when the dioxylic acid ester compound (0) is allowed to act on this.

In the definition of the dioxylic acid ester compound (0) used in this reaction, examples of the esterified carpoxy group represented by R2 include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isobropoxycarbonyl, butoxycarbonyl, tertiary Alkoxycarbonyl such as butoxycarbonyl, benzyloxycarbonyl, hexyloxycarbonyl, phenoxycarbonyl,
Aryloxycarbonyl such as trioxycarbonyl,
Examples include aralkyloxycarbonyl such as benzyloxycarbonyl and phenethyloxycarbonyl, and X2
Examples of the acid group represented by include halogens such as chlorine and bromine. This reaction is preferably carried out in the presence of a base, and examples of the base include "alkali metals such as sodium and potassium, alkaline metals such as alkali metals such as magnesium and calcium, or their hydroxides," carbonates, Inorganic bases such as bicarbonates, quaternary ammonium hydroxides such as trimethylbenzylammonium hydroxide, trialkylamines such as trimethylamine and triethylamine, dialkylanilines such as dimethylaniline and diethylaniline, pyridine, quinoline, etc. Examples include organic bases, and these can be used in combination.The temperature of this reaction is not particularly limited, but it is often carried out under cooling or around room temperature.

The reaction product obtained in this way, the 2-monotransformed thioaniline compound (m), can be led to the target compound (W) by subjecting it to a ring-opening reaction in the presence of an acid catalyst, without using it alone. However, good results are often obtained if the target compound (W) is led to the target compound (W) by isolation and then subjecting it to a ring-closing reaction in the presence of a catalyst.

The acid catalyst used in this reaction is preferably a strong acid such as sulfuric acid, hydrochloric acid, or phosphoric acid, but is not particularly limited thereto. This reaction is usually carried out in a solvent, and the solvent may be any solvent that does not adversely affect this reaction, such as water, methanol, benzene, xylene, organic acids such as diic acid, acetic acid, and propionic acid. . The temperature of this reaction is not particularly limited, but it is usually carried out under heating at about the boiling point of the solvent.

Next, the present invention will be explained with reference to examples. Example 1 (i) - Sodium disulfide prepared by dissolving 36.2 parts of sodium sulfide (9 hydrate) and 4.6 parts of sulfur in 120 parts of water under a heated pestle. The solution was added dropwise to a mixture of 54.9 parts of 2,5-dichloronitrobenzene dissolved in 172 parts of acetone and 23 parts of water while heating under reflux for 90 minutes.

After the dropwise addition, the reaction solution was heated for 30 minutes and the acetone was removed under reduced pressure to obtain a solution containing bis(2nitro-4-chlorophenyl) disulfide.

Next, a solution prepared by dissolving 126 parts of sodium sulfide (nonahydrate) in 80 parts of water was added all at once, and after heating under reflux for 5 hours in a bath at 140°C, the oil was removed, cooled on ice, and diluted with 300 parts of ice water.
After adding the chloride, 6.8 g of a 35% methanol solution of trimethylbenzylammonium hydroxide was added.
Next, while keeping the mixture cooled at 6-7 DEG C., ethyl chloroformate 461' was added dropwise over a period of 45 minutes, after which the cooling was stopped and the mixture was stirred at room temperature for 30 minutes. Take the precipitated crystals in a furnace and add 300 ml of water.
After washing with 150% of diisopropyl ether and 150% of diisopropyl ether, 61.0% (92.5%) of 2-ethoxycarbonylthio-5-chloroaniline was obtained. (When this product is recrystallized from benzene, it becomes white needle-like crystals with mP of 146-1470.) (i}-'.} 23.6 hours of sodium sulfide (nonahydrate) and 0.54 hours of sodium hydroxide in 20 minutes of water. Dissolve the secretion under heating at 60qC, then add 2
- Add 10.0 mm of bis(2-nitro-4-chlorophenyl) disulfide made from 5-dichloronitrobenzene and sodium disulfide at the same temperature, and when heated in a 140 ounce oil bath, it reacts violently and refluxes. 50% of the mixture
After heating under reflux for a minute, the oil bath was removed, the mixture was cooled on ice, and 30% of water was added, followed by a 40% methanol solution of trimethylbenzylammonium hydroxide overnight. Then 5-6
Add 8.6 mL of ethyl chloroformate to this while keeping it cool at 4℃.
After dropping for 0 minutes, stop cooling and let the mixture stand at room temperature for 30 minutes. The precipitated crystals are collected in a furnace, washed with 25 parts of diisopropyl ether, and then dried to obtain 11.2 parts of 2-ethoxycarbonylthio-5-chloroaniline (yield: 91%). (ii) 7.5% of the 2-ethoxycarbonylthio-5-chloroaniline obtained in (i)-' above was mixed with 9% of meta/-2' of concentrated sulfuric acid. When added to a mixture of the following substances and heated under reflux for 40 minutes, crystals precipitate.

After cooling on ice and adding 50 parts of water, the crystals are taken out in a furnace and dissolved in a solution prepared by dissolving 1.7 parts of sodium hydroxide in 150 parts of water at room temperature. After stirring this for 3 minutes, 2 drops of a 20% hydrogen peroxide aqueous solution were added, followed by treatment with activated carbon, filtering in an oven, and the solution was adjusted to pH 7 with hydrochloric acid. When the precipitated crystals are collected in a furnace and dried, mp232.5 - 234.8℃
5.0 ml of 5-chloro-2-penzothiazolinone (yield: 83%) was obtained.

Example 2 Example 1 (i}-[i is (i)-'.

100 g of 2-ethoxycarponylthio-5-chloroaniline obtained by the simultaneous treatment was dissolved in 100 g of xylene at 90 g.
After adding 2' at once at the same temperature, the mixture was heated under reflux for 29 minutes. The reaction solution was cooled on ice, 50% of water was added, and the precipitated crystals were collected. These crystals are combined with the crystals attached to the reaction vessel and dissolved in a solution containing 3.6 parts of sodium hydroxide in 150 parts. Next, a small amount of xylene is added to this, shaken, and the aqueous layer is separated, treated with activated carbon for 0.6 hours, and then adjusted to pH 7 with hydrochloric acid. The precipitated crystals are collected in a furnace,
When dried, mp232.6-2 milk. 6.68 g (total % yield) of 5-chloro-2-penzothiazolinone are obtained at 8°C. Example 3 (i) 2-aminothiophenol (bp 5.5 Kazehi Hina 0
-9ro) 500 mg of sodium hydroxide was dissolved in a solution of 16 mg of sodium hydroxide and 400 mg of water, and then 150 mg of diethyl ether was added to the solution.
After dripping for 60 minutes under ice-cold condensation, the mixture was cooled for 3 times at room temperature.

After the reaction, the diethyl ether layer is separated, and the aqueous layer is further extracted with diethyl ether. The diethyl ether layers were combined and the solvent was distilled off to obtain 75.8 g of oily 2-ethoxycarponylthioaniline (yield: 96.1%). (ii
) Add 32.5 liters of concentrated hydrochloric acid to 5.8 liters of the 2-ethoxycarbonylthioaniline obtained in (i) above, and heat under reflux for 4 hours in a bath at 120°C.

Claims (1)

[Claims] 1 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 means hydrogen, halogen, alkyl group, trihalomethyl group, or alkoxy group, and R_2 means esterified carboxy group ) is subjected to a ring-closing reaction in the presence of an acid catalyst to form a 2-substituted thioaniline compound represented by the general formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (in the formula, R_1 has the same meaning as before). A method for producing a 2-benzothiazolinone compound, the method comprising obtaining a benzothiazolinone compound. 2 General formula▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1 means hydrogen, halogen, alkyl group, trihalomethyl group, or alkoxy group, and X_1 means halogen.) Metal, metal sulfide, and then the general formula X_2-R_2 (wherein R_2 is an esterified carboxy group,
(means an acid residue, respectively) is reacted with a dioxylic acid ester compound represented by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (wherein R_1 and R_2 have the same meanings as before) A substituted thioaniline compound is prepared, which is then subjected to a ring-closing reaction in the presence of an acid catalyst to form the general formula ▲mathematical formula, chemical formula,
There are tables, etc. ▼ (In the formula, R_1 has the same meaning as before) A method for producing a 2-benzothiazolinone compound, which is characterized by obtaining a 2-benzothiazolinone compound represented by the following.