JPH06128218A - Production of 5-amino-2-chloro-4-fluorothiophenol and its intermediate - Google Patents

Abstract

PURPOSE:To obtain two new specific carbamic acid esters useful as a starting compound for 5-amino-2-chloro-4-fluorothiophenol useful as an intermediate for a herbicide. CONSTITUTION:An N-[4-chloro-5-(chlorosulfonyl)-2-fluorophenyl]carbamic acid ester of formula I (R is lower alkyl) and an N-(4-chloro-2-fluoro-5- mercaptophenyl) carbamic acid ester of formula II. The compound of formula I is reduced to give the compound of formula II. The compound of formula II is hydrolyzed to give a 5-amino-2-chloro-4-fluorothiophenol of formula III. The compound of formula I is readily obtained from 2-fluoroaniline by three- stage reaction according to the reaction formula.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention relates to tetrahydrophthalimide herbicides (for example, European Patent Publication No. 1264).
19), urazole herbicides (see, for example, JP-A-6-61
1-76487), thiadiazabicyclononane herbicides (for example, European Patent Publication No. 273417), and a method for producing 5-amino-2-chloro-4-fluorothiophenol, which is useful as an intermediate. It provides the intermediate.

[0002]

2. Description of the Related Art Conventionally, as a method for producing 5-amino-2-chloro-4-fluorothiophenol, Japanese Patent Laid-Open No. 61-40261 and US Pat. No. 4,613,675 have been disclosed. Japanese Patent Laid-Open No. 1-16
Several methods are known, as described in Japanese Patent No. 8662 and Japanese Patent Laid-Open No. 4-108770. However, the conventional method has problems that it has a large number of steps, or that a large amount of heavy metal or heavy metal compound, which causes a problem of post-treatment, must be used as a reactant.

[0003]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that 5-amino-2-
The industrially advantageous production method of chloro-4-fluorothiophenol was found, and the present invention was completed.

That is, the gist of the present invention is to provide N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamic acid esters represented by the following general formula [I] and the following general formula [II ] N- (4-
Chloro-2-fluoro-5-mercaptophenyl) carbamic acid esters and N- (4-chloro-5- (chlorosulfonyl) -2- represented by the following general formula [I]:
N- (4 represented by the following general formula [II] is obtained by reducing fluorophenyl) carbamic acid esters.
-Chloro-2-fluoro-5-mercaptophenyl) carbamic acid esters, which are then hydrolyzed, which is a method for producing 5-amino-2-chloro-4-fluorothiophenol.

[Chemical 3] (In the above formula, R represents a lower alkyl group)

[Chemical 4] (In the above formula, R represents a lower alkyl group)

The present invention will be described in detail below. The compounds of the present invention are represented by the above general formulas [I] and [II],
The substituent R is a lower alkyl group such as methyl, ethyl, propyl and butyl. Compound [I] can be produced from 2-fluoroaniline according to the following formula. In the reaction formula, chlorosulfonylation using chlorosulfonic acid in the third step is carried out, for example, under reaction conditions according to the method described in JP-A-62-33148 and JP-A-62-33149, particularly It can be suitably performed. The reaction scheme of the method for producing 5-amino-2-chloro-4-fluorothiophenol [III] of the present invention is as follows.

[0006]

[Chemical 5] (In the formula, R 1 has the same meaning as described above.)

In the above reaction formula, the reduction reaction to the compound [II] is carried out, for example, by heating the red phosphorus and iodine compounds together with the mineral acid to activate them, and adding the compound [I] thereto. The amount of the reactant used is 1.5 to 3 times the molar amount of red phosphorus based on the compound [I], and the iodine compound (iodine, potassium iodide, hydrogen iodide, etc.) is 0.05 to 0.3.
Double molar amount, mineral acid (hydrochloric acid, hydrobromic acid, hydroiodic acid, etc.)
A molar amount of 0.2 to 0.5 times is preferable. Activation is usually achieved by heating to 90-110 ° C for 0.5-1.5 hours. The reduction reaction can be carried out without a solvent, but it is usually carried out by heating and refluxing in an inert solvent. The solvent used is benzene,
Aromatic hydrocarbons such as toluene, xylene and chlorobenzene are particularly suitable. In this reaction, zinc, tin, tin (II) chloride, lithium aluminum hydride or the like can be used as a reducing agent. Compound [II]
The hydrolysis reaction is usually performed in an aqueous base solution at room temperature or under heating. As the base used, inorganic bases such as sodium hydroxide, potassium hydroxide and calcium hydroxide are suitable, and the amount thereof is usually 2 to 5 times the molar amount of the compound [II].

[0008]

EXAMPLES The present invention will be specifically described below with reference to examples. Reference Example 1 Synthesis of ethyl N- (4-chloro-2-fluorophenyl) carbamate Ethyl N- (2-fluorophenyl) carbamate 5
Dissolve 5.0 g in 300 ml of methanol and, under ice-cooling, keep the reaction temperature at 10 ° C or lower and stir chlorine 2 while stirring.
Blow 2.1g. After the completion, stirring was continued for 0.5 hour, and then the reaction mixture was poured into 600 ml of ice water. The precipitated crystals are collected by filtration, washed with water and dried, and N- (4-chloro-2-
Ethyl fluorophenyl) carbamate 60.6 g (9
1.2%) was obtained. The physical properties of the obtained compound are as follows.

[0009]

Table 1 Melting point 60.4-61.3 ° C NMR (δ, CDCl ₃ ) 1.32 (t, 3H), 4.
24 (q, 2H), 6.81 (bs, 1H), 7.0
7.2 (m, 2H), 8.05 (bt, 1H) Methyl N- (4-chloro-2-fluorophenyl) carbamate was also obtained by the same method as above. The physical properties of the obtained compound are as follows.

Table 2 Melting point 77.1-78.7 ° C NMR (δ, CDCl ₃ ) 3.80 (s, 3H), 6.
8 (bs, 1H), 7.0 to 7.2 (m, 2H), 8.
04 (bt, 1H)

Example 1 Synthesis of ethyl N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamate 43.5 g of ethyl N- (4-chloro-2-fluorophenyl) carbamate was cooled with ice. Chilled chlorosulfonic acid 11
Added to 6.5 g. After warming to room temperature, under stirring, 60
80.0 g of% fuming sulfuric acid was added dropwise while maintaining the reaction temperature at 20 to 35 ° C. After the completion of stirring for 4 hours at room temperature,
The reaction mixture was poured into 1000 g of ice water. The precipitated solid was extracted with ethyl acetate, washed with water and then saturated brine,
It was dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure, hexane was added for crystallization, and 39.1 g (61.9%) of ethyl N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamate was obtained. The physical properties of the obtained compound are as follows.

[0011]

[Table 3] Melting point 88.0 to 89.0 ° C NMR (δ, CDCl ₃ ) 1.35 (t, 3H), 4.
30 (q, 2H), 6.96 (bs, 1H), 7.38
(D, 1H), 9.06 (bd, 1H)

Example 2 Synthesis of methyl N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamate 10.2 g of methyl N- (4-chloro-2-fluorophenyl) carbamate was added to ice. Chilled chlorosulfonic acid 29.
Added to 1 g. After the temperature was raised to room temperature, 20.0 g of 60% fuming sulfuric acid was added dropwise with stirring while maintaining the reaction temperature at 20 to 35 ° C. After stirring at room temperature for 2 hours, thionyl chloride 5.
After 95 g was added dropwise and stirring was continued for another 2 hours, the reaction mixture was poured into 250 g ice water. The precipitated solid was extracted with ethyl acetate, washed with water and then saturated brine, and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure and hexane was added for crystallization to give methyl N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamate (10.7 g, 70.8%). The physical properties of the obtained compound are as follows.

Table 4 Melting point 116.0-117.0 ° C NMR (δ, CDCl ₃ ) 3.85 (s, 3H), 7.
02 (bs, 1H), 7.39 (d, 1H), 9.04
(Bd, 1H)

Example 3 Synthesis of ethyl N- (4-chloro-2-fluoro-5-mercaptophenyl) carbamate A mixture of 6.19 g of red phosphorus, 4.10 g of 18% hydrochloric acid and 5.08 g of iodine was stirred. The mixture was heated to reflux for 0.5 hour. A solution of 31.6 g of ethyl N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamate in 100 ml of toluene was added dropwise to this, and after completion, heating with stirring for 2.5 hours, Refluxed. After cooling, the insoluble material was filtered off and the organic layer was separated. The organic layer was washed with water and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and N-
22.3 g (89.4%) of ethyl (4-chloro-2-fluoro-5-mercaptophenyl) carbamate was obtained. It was purified by recrystallization from hexane. The physical properties of the obtained compound are as follows.

[0014]

[Table 5] Melting point 53.2-54.2 ° C NMR (δ, CDCl ₃ ) 1.33 (t, 3H), 3.
85 (s, 1H), 4.24 (q, 2H), 6.76
(Bs, 1H), 7.12 (d, 1H), 8.18 (b
d, 1H)

Example 4 Synthesis of methyl N- (4-chloro-2-fluoro-5-mercaptophenyl) carbamate A mixture of 0.1 g of red phosphorus and 0.2 g of 55% hydroiodic acid was heated under reflux for 1 hour. did. To this, toluene 10m
1, and then 0.50 g of methyl N- (4-chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamate was added little by little, and after completion, the mixture was heated under reflux for 2 hours with stirring. After cooling, the insoluble material was filtered off and the organic layer was separated. The organic layer was washed with water and dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and methyl N- (4-chloro-2-fluoro-5-mercaptophenyl) carbamate.
29 g (74%) were obtained. It was purified by recrystallization from hexane. The physical properties of the obtained compound are as follows.

[0016]

Table 6 Melting point 74.6-75.6 ° C NMR (δ, CDCl ₃ ) 3.81 (s, 3H), 3.
85 (s, 1H), 6.77 (bs, 1H), 7.13
(D, 1H), 8.18 (bd, 1H)

Example 5 Synthesis of 5-amino-2-chloro-4-fluorothiophenol 22.3 g of ethyl N- (4-chloro-2-fluoro-5-mercaptophenyl) carbamate was added to sodium hydroxide 11. 3 g of water was added to 100 ml of a solution and stirred,
Heated to reflux for 1 hour. After cooling, a trace amount of insoluble matter was removed by activated carbon treatment. The pH was adjusted to 5 to 6 by adding hydrochloric acid, and the precipitated crystals were collected by filtration, washed with water and dried to give 14.2 g (91.1) of 5-amino-2-chloro-4-fluorothiophenol.
%) Was obtained. The physical properties of the obtained compound are as follows.

[Table 7] Melting point 61.8-62.4 ° C NMR (δ, CDCl ₃ ) 3.71 (bs, 2H),
3.76 (s, 1H), 6.75 (d, 1H), 7.0
4 (d, 1H)

[0018]

INDUSTRIAL APPLICABILITY According to the compound and the production method of the present invention, 5-amino-2-chloro-4-fluorothiophenol useful as an intermediate for herbicides can be easily produced, and its industrial value is high.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Chikako Ota 1000 Kamoshida-cho, Midori-ku, Yokohama, Kanagawa Sanryo Kasei Co., Ltd.

Claims (3)

[Claims] 1. N- (4-represented by the following general formula [I]:
Chloro-5- (chlorosulfonyl) -2-fluorophenyl) carbamic acid esters. [Chemical 1] (In the above formula, R represents a lower alkyl group) 2. N-represented by the following general formula [II]:
(4-Chloro-2-fluoro-5-mercaptophenyl) carbamic acid esters. [Chemical 2] (In the above formula, R represents a lower alkyl group) 3. The N- (4-chloro-5 according to claim 1.
The N- (4-chloro-2-fluoro-5-mercaptophenyl) carbamic acid ester according to claim 2 is obtained by reducing-(chlorosulfonyl) -2-fluorophenyl) carbamic acid ester, and then A method for producing 5-amino-2-chloro-4-fluorothiophenol, which comprises hydrolyzing this.