JPS62238284A - Tetrahydro-2h-indazole derivative and production thereof - Google Patents

Abstract

NEW MATERIAL:2-(2-Amino-6-fluorobenzothiazol-5-yl)-3-chloro-4,5,6,7-tetrah ydro- 2H-indazole. USE:An intermediate for tetrahydro-2H-indazole derivatives which are herbicides. PREPARATION:2-(5-Amino-2-fluorophenyl)-3-chloro-4,5,6,7-tetrahydro-2H- indazole is reacted with a thiocayanate, e.g. sodium thiocyanate, etc., preferably at 1:1-10 equivalent ratio, normally in a solvent, e.g. aqueous acetic acid, etc., and a halogen, e.g. Cl, Br, etc., is then reacted therewith. The reaction condition is preferably 0-50 deg.C and 1-100hr.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to 2-(2-amino-6-fluorobenzothiazol-5-yl)-3- which is important as an intermediate for compounds having herbicidal activity. 10Rho 4.5,6.7-tetrahydro-2a-indazole and its manufacturing method.

<Prior Art> Until now, JP-A-52-51865 and other publications have described the use of ζtetrahydro-2H-indazole derivatives as active ingredients in herbicides.

<Problems to be Solved by the Invention> However, these compounds are not necessarily satisfactory because their herbicidal activity is insufficient or their selectivity between crops and weeds is poor.

Means for Solving the Problems> The present inventors have made extensive studies in order to develop a compound with strong herbicidal activity in this situation, and have found that 6-6 is added to the 2nd position of tetrahydro-2-indazole. -Fluoro-2(8
As a result of discovering that a compound having an I()-benzothiazolone-5-yl group is a compound having excellent herbicidal activity with few of the above-mentioned drawbacks and conducting intensive studies on its production method, the 2-(2- Amino-6-fluorobenzothiazol-5-yl)-8-chloro-4,5,6
, 7-tetrahydro-2u-indazole was discovered to be an essential intermediate for the above-mentioned compound having herbicidal activity, leading to the present invention.

That is, the present invention provides 2-(2-amino-6-fluorobenzothiazol-6-yl)-8-chloro-4,5,6
, 7-titrahydro-211-indazole (hereinafter referred to as the compound of the present invention) and a method for producing the same.

The compound of the present invention can be obtained by diazotizing, diazolyzing, and then alkylating, alkenylating, alkynylating, or alkoxyalkylating the compound according to the route shown below. group, alkenyl group, alkynyl group or alkoxyalkyl group. ] As an intermediate thereof, the above general formula [I] is derived.
The tetrahydro-2H-indazole derivative represented by the formula does not cause any problematic phytotoxicity to major crops such as corn, wheat, rice, soybean, and cotton, and has sufficient herbicidal activity against many weeds.

Below, M! of the present invention! Explain the law in detail.

The compounds of the present invention quasi-2-(5-amino-2-
fluorophenyl)・-3-chloro-4t5t6,7-
It is obtained by reacting y-trahydro-2-indazole with a thiocyanate and then reacting with a halogen.

In the production method f of the present invention, examples of the thiocyanate that can be used in the reaction include sodium thiocyanate, potassium thiocyanate, ammonium thiocyanate, etc., and examples of the halogen include bromine, carrier, etc.

Examples of solvents that can be used in the reaction include aqueous acetic acid, aqueous hydrochloric acid, and aqueous sulfuric acid.

The reaction temperature and reaction time of the reaction are usually 0 to 50
The purpose can be fully achieved within the range of 1 to 100 hours.

At this time, the amount of reagents used in the reaction is 2-(5-amino-2-fluorophenyl)-8-chloro-4,5,6,
The thiocyanate is 1 to 10 equivalents, and the halogen is 1 to 10 equivalents per 1 equivalent of 7-titrahydro 2L (-indazole).

After the reaction is completed, the reaction solution is neutralized, and the resulting crystals are harvested and air-dried, or if necessary, purified by recrystallization, chromatography, etc., to achieve the objective of the present invention. A compound is obtained.

The raw material compound 2-(5-amino-2-fluorophenyl)-8-chloro-4,5°6.7-tetrahydro-2-indazole can be obtained, for example, by the following route.

That is, by reacting 2-fluoro-5-nitrophenylhydrazine and 2-cyclohexanonecarboxylic acid ester, a hexahydro-3-indazole derivative represented by the above formula [11] is obtained. By reacting the hexahydro-8-indazole derivative represented by the formula [II] with a chlorinating agent in the presence of a dehydrohalogenating agent if necessary, the above formula +, I
The tetrahydro-2H-indazole derivative represented by I[] is then reacted with the tetrahydro-2-indazole derivative represented by the formula fml obtained above with a reducing agent to obtain the tetrahydro-2H-indazole derivative represented by the above formula [y]. A tetrahydro-2H-indazole derivative is obtained.

The method for producing the above-mentioned raw material compound will be explained in detail below.

In the reaction of 2-fluoro-5-nitrophenylhydrazine and 2-cyclohexanonecarboxylic acid ester,
Examples of the 2-cyclohexanone carboxylic acid ester that can be used in the reaction include methyl ester, ethyl ester, etc. of the carboxylic acid.

In addition, in this reaction, solvents that can be used include acetic acid,
Examples include aliphatic carboxylic acids such as propionic acid.

At this time, the reaction temperature and reaction time are typically 2
The range of 0 to 120''C, between 1 and 241 degrees Celsius, is enough to reach the target.

jI of the reagent used in the reaction is 1.0 to 1.5 equivalents of 2-cyclohexanonecarboxylic acid and stellate per 1 equivalent of 2-fluoro-5-nitrophenylhydrazine.

After the reaction is complete, the reaction solution is poured into ice water, and the resulting crystals are poured into P
or, if necessary, by further purifying by operations such as recrystallization chromatography, the above formula
A hexahydro-3H-indazole derivative represented by is obtained.

Hexahydro-8 represented by formula [II] obtained above
In the reaction between H-indazole derivative and chlorinating agent,
Examples of the chlorinating agent that can be used in the reaction include phosgene, oxalic acid chloride, trichloromethyl chlorocarbonate, phosphorus oxychloride, and thionyl chloride.

Examples of the dehalogenating agent include organic bases such as pyridine, l-ethylamine, and N,N-diethylaniline. The amount of reagents to be used in the reaction is 1.0 to 15 to 1.0 to 15 t of the chlorinating agent per 1 t of hexahydro-811-indazole represented by 2[111, and a catalytic amount of the dehalogenating agent. ~Aliphatic hydrocarbons such as ligeroin, aromatic hydrocarbons such as toluene, bembin, xylene, halogenated hydrocarbons such as chloroform, carbon tetrachloride, dichloroethane, tetrachloroethane, chlorobenzene, dichlorobenzene, etc. A1 diisopropyl ether, dioxane, ethylene glycol Examples include ethers such as dimethyl ether, pyridine, triethylamine, tertiary amines such as N,N-diethylaniline, tributylamine, and N-methylmorpholine, or mixtures thereof.

The reaction temperature of the reaction is in the range of 20 to 200"C, preferably 80 to 130"C, and the reaction time is in the range of 1 to 24"C.
The range is 0 hours.

The reaction pressure for this reaction is typically normal pressure -50 to 9/9.
, j.

After the completion of the reaction, the reaction solution is subjected to post-treatments such as concentration, or if necessary, is purified by operations such as recrystallization and chromatography to obtain the tetrahydro-2-indazole derivative represented by the formula [ml]. can get.

The formula obtained above [tetrahydro-2 represented by nil
- In the reaction between an indazole derivative and a reducing agent, examples of the reducing agent that can be used in the reaction include iron powder, zinc tin powder, ferrous chloride, zinc chloride, stannous chloride, etc. Examples of solvents that can be used in the reaction include aqueous acetic acid, aqueous hydrochloric acid, and aqueous sulfuric acid.

Note that a solvent such as ethyl acetate may be used in combination if necessary.

The strength of the reagent used in the above reaction is such that the reducing agent is used in an amount of 3 to 30 equivalents, preferably 5 to 1 equivalent of the tetrahydro-2-indazole derivative represented by the above formula [111].
~20 years old.

At this time, the reaction temperature and reaction time of the reaction are usually 6
The purpose can be sufficiently achieved within the range of 0 to 120°C for 1 to 24 hours.

After the reaction is completed, the reaction solution is separated from the residue by P, the P solution is extracted with an organic solvent, the extracted solution is washed with water, aqueous sodium bicarbonate, etc., and then subjected to post-treatment such as shrinkage, or if necessary, By purifying through operations such as recrystallization and chromatography,
A tetrahydro-2fi-indazole derivative represented by formula [M] is obtained.

In addition, 2-fluoro-5-nitrophenylhydrazine, which is a raw material compound, is derived from 2-fluoro-5-nitroaniline by J, Chem, 8oe, e (C) *19
It can be manufactured by the manufacturing method described in 70 2106°.

<Example> Hereinafter, the present invention will be explained in more detail with reference to production examples and reference examples.

Production Example 2 - 22.97 y of (5-amino-2-fluoropheneyk)-3-chloro-4,5,6,7-tetrahydro-2H-indazole was dissolved in 79.58 y of 95% aqueous butyric acid, and the solution was dissolved at room temperature. This 4% contains ammonium thiocyanate 15.92
Added y.

Ammonium thiocyanate is dissolved in y, = m, a, and a bath solution in which 15.89y of bromine is diluted with 23.77N of acetic acid is added to 1
The mixture was added dropwise over a period of 45 minutes. - After leaving it overnight, heat it to IOO''C, add 173 ml of hot water, and strain it under heat for 2 hours.After the solution has cooled down, neutralize it with sodium carbonate, and air-dry the precipitated crystals for 2-(2 hours). -amino-6-fluorobenzothiazol-5-yl)-3-chloro-4,5,6,7-
Tetrahydro-2a-indazole8. 'lTlfg got.

m, p, 212.4"C Reference example 1 2-fluoro-5-nitrophenylhydrazine 58.9
5y and ethyl 2-cyclohexanonecarboxylate 58.6
5f was dissolved in vinegar @109wj and heated under reflux for 4 hours. After the reaction mixture had cooled down, it was poured into ice water, and the precipitated crystals were collected, washed with water and hexane, and air-dried to give 2-(
2-Fluoro-5-nitrophenyl)-1,2,4,5
,6,7-hexahydro-8H-indazol-3-one f! It was.

m, p, 220.0''C Reference Example 2 2-(2-fluoro-5-nitrophenyl)-1,2,4,5,6,7-hexahydro-311 obtained above
-66.87y of indazol-8-one to 12y of toluene
5m and 1s2-dichloroethane 175-, add trichloromethyl chlorocarbonate 71.57F, in autoclave 120~1dO"C, 9/c to 25,
A reaction was carried out for 3 hours. After the reaction mixture had cooled down, the solvent was distilled off, and the resulting residue was subjected to silica gel column chromatography (developing solvent: acetate, ethyl:hexane, and
), 3-chloro-2-(2-fluoro-5-
Nitrophenyl)-4,5,6,7-tetrahydro-2
30.451 of H-indazole was obtained.

m, ri, 109.1″C C Reference iron powder 28.75y was suspended in 5% acetic acid water 57.5y,
It was heated to 80°C. To this, 3-chloro-2-(2-fluoro-5-nitrophenyl)-4,5 obtained above
, 6,7-tetrahydro-2H-indazole 8G, 4
5F to 103% acetic acid and 108% ethyl vinegar. The filtered bath liquid was added to d, and heated under reflux at 60-80"C for 3 hours. Cooled condensate and ethyl acetate were added, and 9U'ib,
The P solution was extracted with ethyl acetate. The extract was washed with water, then 1 sulfur water, dried, concentrated, and 2-(5-amino-
2-fluorophenyl)-3-chloro-4,5,6,7
-Titrahydro 211i --(ndazole 22.9
7) was obtained.

Claims (2)

[Claims] (1) 2-(2-amino-6-fluorobenzothiazol-5-yl)-3-chloro-4,5,6,7-tetrahydro-2H-indazole. (2) 2-(5-amino-2-fluorophenyl)-3
2-(2-amino-
A method for producing 6-fluorobenzothiazol-5-yl)-8-chloro-4,5,6,7-tetrahydro-2H-indazole.