JP3310104B2 - Method for producing 2-aminothiophenols - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing 2-aminothiophenols, which are compounds useful as intermediates for pharmaceuticals, agricultural chemicals and organic chemistry.

[0002]

2. Description of the Related Art As a conventional method for producing 2-aminothiophenols, a method of hydrolyzing 2-aminobenzothiazole with potassium hydroxide is disclosed in U.S. Pat.
No. 02142. In this method, although the raw materials are easily available, the hydrolysis temperature is 200 to 280 ° C.
This is not economical, and the reaction itself is insufficient in yield. Therefore, it is industrially and economically disadvantageous, for example, it is necessary to remove unreacted raw materials after completion of the reaction.

As an example of adding a glycol as an accelerator for an organic reaction, Japanese Patent Application Laid-Open No. 52-111501 discloses
There is a number. According to this method, ethylene glycol, polyethylene glycol and the like are added.

[0004]

SUMMARY OF THE INVENTION The present invention has been made in view of the conventional problems, and is a simpler method than the conventional method, and has a high purity, a high yield, and is industrially advantageous. A method for producing aminothiophenols will be disclosed.

[0005]

The present invention is characterized in that, when the 2-aminobenzothiazole represented by the chemical formula (3) is subjected to alkaline hydrolysis, the hydrolysis reaction is carried out in the coexistence of ethylene glycol. A process for producing 2-aminothiophenols represented by the formula (4), wherein 2-aminothiophenols represented by the formula (4) are produced in high purity and high yield. (In the chemical formulas 3 and 4, R is hydrogen, halogen, nitro group or methyl group.)

[0006]

Embedded image

[0007]

Embedded image

In the present invention, unlike the prior art, the reaction should be promoted even with polyethylene glycol or the like. However, in this reaction, the addition of polyethylene glycol was not effective, and the specificity of the reaction was found only for ethylene glycol. It has special features. As the alkali used in the present invention, one or more of potassium hydroxide, sodium hydroxide and lithium hydroxide are selected.

Further, the amount of ethylene glycol in a solvent composed of water and ethylene glycol is determined based on the total amount of the solvent.
5% to 50%. Less than 5% of ethylene glycol
The reaction promoting effect as an additive is weak, and exceeds 50%
If that, since the concentration of relatively water is low, the rate of hydrolysis tends to slow down.

The temperature of the hydrolysis reaction is 80 to 15
It is preferably performed at 0 ° C., more preferably at 110 ° C.
~ 130 ° C. At 80 ° C. or lower, hydrolysis efficiency is poor, and at 150 ° C. or higher, by-products of reaction impurities are observed.

[0011]

In the present invention, in the synthesis reaction of 2-aminothiophenols represented by the chemical formula 4, unlike the above-mentioned U.S. Pat. No. 3,102,142, ethylene glycol is added as an additive for accelerating the hydrolysis reaction. To complete the reaction is a finding obtained by the present invention for the first time, and the present invention has significance in this respect.

Since the temperature of the hydrolysis reaction is a moderate temperature of 80 to 150 ° C., decomposition of the synthesized product and by-product of impurities are minimized, and the yield of the target product is high. Since the reaction is complete, there is no need to separate unreacted substances, and since the reaction additives, ethylene glycol and alkali, are water-soluble, high purity products can be obtained by washing the obtained target product with water. It also has features such as

[0013]

【Example】

[Example 1] 66 g of 2-aminobenzothiazole,
40 g of water, 73 g of potassium hydroxide and 10 g of ethylene glycol were added, and the mixture was heated and stirred at 125 ° C. for 15 hours. After the reaction, this was cooled to 30 ° C., diluted with 100 ml of water, filtered, neutralized with hydrochloric acid, and further extracted with toluene. The toluene of the obtained toluene extract was distilled off under reduced pressure, and then vacuum distillation was performed at 30 mmHg and 125 ° C. to obtain 54.2 g of 2-aminothiophenol (89.4% of the theoretical yield). . The purity of the target product by gas chromatography analysis was 99.1%.

Example 2 81 g of 6-chloro-2-aminobenzothiazole, 40 g of water, 73 g of potassium hydroxide and 10 g of ethylene glycol were added, and the mixture was heated and stirred at 125 ° C. for 15 hours. After the reaction, this was cooled to 30 ° C., diluted with 100 ml of water, filtered, neutralized and crystallized with hydrochloric acid, and the obtained crystals were washed with water, dried and washed with 5-chloro-2-amino acid. Thiophenol 64.
2 g (91.7% of theoretical yield) were obtained. The purity of the target product by gas chromatography analysis was 99.2%, m.p.
p. 77.0-79.5 ° C.

[Comparative Example 1] In the alkaline hydrolysis according to Example 1, no ethylene glycol was added and the additive was changed. Table 1 shows the purity and yield of the obtained 2-aminothiophenol together with the results of Example 1.

[0016]

[Table 1] Additives Unreacted substances Purity (%) Yield (%) No addition Yes 67.8 65.6 Ethylene glycol None 99.1 89.4 Polyethylene glycol None 81.2 72.0 Polypropylene glycol None 79.7 75.3

[Comparative Example 2] When alkaline hydrolysis was carried out according to Example 2, ethylene glycol was not added, and the additive was changed. 5-chloro-2 obtained
Table 2 shows the purity and yield of aminothiophenol together with the results of Example 2. In Table 2, BTE
AC refers to benzyltriethylammonium chloride as a phase transfer catalyst.

[0018]

[Table 2] Additive Unreacted substance Purity (%) Yield (%) No addition Yes 73.1 65.3 Ethylene glycol None 99.2 91.7 Polyethylene glycol None 82.5 78.4 Polyphenylene glycol None 88.1 85.8 n-Phthyl cellulose Yes 81.5 87.3 BTEAC Yes 77.3 78.0

[0019]

In the alkaline hydrolysis of 2-aminobenzothiazoles, the addition of ethylene glycol other than ethylene glycol does not complete the reaction, leaving unreacted substances, or necessitating a high-temperature reaction or a prolonged reaction time. For this reason, impurities were produced as by-products, and remarkable differences were observed in purity and yield as compared with the case where ethylene glycol was added. When 2-aminobenzothiazoles are alkali-hydrolyzed to synthesize 2-aminothiophenols, the reaction can be terminated under relatively mild conditions by adding ethylene glycol. In addition, the target reactant was obtained with high purity and high yield, and the effect of ethylene glycol was confirmed.

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07C 323/34 C07C 319/02 CA (STN) CASREAT (STN) REGISTRY (STN)

Claims (2)

(57) [Claims] 1. The method according to claim 1, wherein when the 2-aminobenzothiazole represented by the chemical formula (1) is subjected to alkaline hydrolysis, no reducing agent is present.
Below, 5% to 50% of the total amount of ethylene glycol
Coexistence and alkali hydrolysis temperature is 80-150
A method for producing 2-aminothiophenols represented by Chemical formula 2, Embedded image (Where R is hydrogen, halogen, a nitro group, or a methyl group.) (Where R is hydrogen, halogen, nitro group, methyl group) 2. The alkali is at least one selected from potassium hydroxide, sodium hydroxide, and lithium hydroxide.
The production method according to claim 1, which is at least one kind.