EP1131300A2

EP1131300A2 - Method for producing 5-amino-3-(thio)carbamoylpyrazoles

Info

Publication number: EP1131300A2
Application number: EP99955971A
Authority: EP
Inventors: Holger Weintritt; Bernd Alig; Reinhard Lantzsch
Original assignee: Bayer AG
Current assignee: Bayer AG
Priority date: 1998-11-20
Filing date: 1999-11-10
Publication date: 2001-09-12
Also published as: ZA200103144B; AU1270400A; JP2002530382A; HK1041002A1; CN1326446A; DE19853560A1; IL142643A0; KR20010085955A; WO2000031043A2; WO2000031043A3

Abstract

The invention relates to a novel method for producing 5-amino-3-(thio)carbamoylpyrazoles.

Description

Process for the preparation of 5-amino-3- (thio) carbamoylpyrazo_en

The present invention relates to a new process for the preparation of 5-amino-3- (thio) carbamoylpyrazoles.

It is known that 5-amino-3-carbamoylpyrazoles of the formula (AI)

(with Ar = optionally substituted phenyl or pyridyl; Z = especially halogenoalkyl and m = 0, 1 or 2)

obtained when pyrazole derivatives of the formula (B 1)

(with E = ester grouping)

in the usual way, first with chlorides of the formula (Cl)

implemented and then amidated the derivatives thus obtained on the ester grouping, for example by means of ammonia (cf. for example EP 0 500 209).

It is also known that 5-amino-3-thiocarbamoylpyrazoles of the formula (A2)

obtained if pyrazole derivatives of the formula (B2)

first reacted in the usual manner with chlorides of the formula (C1) and then the derivatives obtained in this way were derivatized on the cyano group using hydrogen sulfide (cf. e.g. DE-A 1 96 50 197, WO 98/28 279).

However, both processes have the disadvantage that, starting from the finished pyrazole ring system, a two-stage reaction sequence is required. In addition, the use of hydrogen sulfide makes use of a toxic, harmless reagent.

It has now been found that 5-amino-3- (thio) carbamoylpyrazoles of the formula (I) - _> -

in which

A stands for N or the grouping C-Hal ', where

Shark represents halogen,

X represents oxygen or sulfur,

Y stands for S, SO or S0 ₂ and

R represents haloalkyl or alkyl,

obtained in a simple manner if pyrazole derivatives of the formula (II)

in which

A, shark and X have the meaning given above,

with halides of the formula (III)

Ha _ "- Y-R (III)

in which

Shark "stands for halogen, especially chlorine or bromine, and

R and Y have the meaning given above,

if appropriate in the presence of a diluent and if appropriate in the presence of a reactant and if appropriate

a) the compounds of the formula (Ia) (X = O) thus obtained

in which

A, Hai, Y and R have the meaning given above,

subsequently reacted with a sulfurizing agent, if appropriate in the presence of a diluent;

or

b) the compounds of the formula (Ib) (Y = S) thus obtained

in which

A, Hai, X and R have the meaning given above, subsequently oxidized with an oxidizing agent, optionally in the presence of a diluent and optionally in the presence of a catalyst.

Formula (I) provides a general definition of the 5-amino-3- (thio) carbamoylpyrazoles which can be prepared according to the invention. Preferred substituents or ranges of the radicals listed in the formulas mentioned above and below are explained below.

A preferably represents N or the grouping C-Hal ", where

Hai 'represents fluorine or chlorine.

Shark is preferably fluorine or chlorine.

X preferably represents oxygen or sulfur.

Y preferably represents S, SO or SO ₂ .

R preferably represents (-C-C ₄ ) haloalkyl having 1 to 9 identical or different halogen atoms from the series fluorine, chlorine and bromine or for (C _] -C) - alkyl.

R particularly preferably represents one of the radicals: -CF- ,, -CHF ₂ , -CF ₂ CH ,,

-CF ₂ CHF ₂ , -CF, CHFC1, -CH ₂ CF "-CH, -CF ₂ C1, -CH ₂ -CF, CHF ₂ , -CF ₂ -CFC1-CF" -C (C1) (CF,) -CF ₂ C1, -C (C1) (CF,) - CI IC1-CF, as well as -CH, and -C ₂ H ₅ .

Compounds of the formulas (IA) or (IB) are most preferred by the process according to the invention.

in which

A, Hai and R have the meaning given above, as well as those compounds in which

A stands for C-Cl,

Shark stands for Cl and

R represents -CF ₃ ,

manufactured.

Surprisingly, in the reaction according to the invention of the pyrazole derivatives of the formula (II) with halides of the formula (III), the compounds of Formula (I) obtained with high selectivity - the expected competitive reaction of the halides on the H ₂ N-CO (S) group cannot be observed (cf., for example, Liebigs Ann. 727 (1969), 22; J. Org. Chem. USSR (Engl. Trans.) \ 967.963; J. Chem. Soc. 1953, 549; Tetrahedron 50 (1994), 5083 and US 24 76 655).

The reaction according to the invention has the advantage that the compounds according to the invention can be obtained in a simple one-step reaction starting from the finished pyrazole ring system. In addition, no hydrogen sulfide is required to produce the thioamide derivatives.

If, for example, 5-amino-3-carbamoyl-l- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and trifluoromethylsulfinyl chloride are used as starting materials and then phosphorus pentasulfide as a sulfurizing agent, the course of the reaction of the process according to the invention and of connection variant (a) can be outlined by the following formula:

Connection ariante (a)

Those to be used as starting materials in the process according to the invention

Pyrazole derivatives are known in some cases (cf. e.g. DE 1 96 50 197 and EP 0 500 209) or are obtainable in a generally known manner.

Not yet known and also the subject of this application are the pyrazole derivatives of the formula (Ha)

in which

Flal and Hai 'have the meaning given above. The pyrazole derivatives of the formula (Ila) are obtained by derivatizing corresponding 3-cyano-pyrazole derivatives in a known manner on the cyano group (cf., for example, EP 0 295 1 17 or the preparation examples).

The halides of the formula (III) which are also to be used as starting materials in the process according to the invention are generally known compounds of organic chemistry.

Inert organic solvents are suitable as diluents for carrying out the process according to the invention. These include in particular aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, gasoline, benzene, toluene, xylene, chlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride; Ethers such as diethyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl or diethyl ether, ketones such as acetone or butanone, nitriles such as acetonitrile or propionitrile; Amides, such as dimethylformamide, dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide, esters, such as ethyl acetate, sulfoxides, such as dimethyl sulfoxide or acids, such as, for example, acetic acid.

The process according to the invention can optionally be carried out in the presence of a reaction auxiliary. Common inorganic or organic bases, furthermore hydrochlorides, tosylates and mesylates of primary, secondary or tertiary amines and hydrochloric acid are suitable as such.

The reaction temperatures can be carried out when carrying out the process according to the invention

Process can be varied over a wide range. In general, temperatures between -20 ° C and + 120 ° C, preferably at temperatures between 0 ° C and + 50 ° C.

To carry out the process according to the invention, per mole of pyrazole

Derivative of formula (II) in general 1.0 to 2.5 mol, preferably 1.0 to 1.5 Mol of halide of the formula (III) and optionally 1.0 to 2.5 mol, preferably 1.0 to 1.5 mol of reaction auxiliaries. The reaction, working up and isolation of the reaction products is carried out according to generally customary methods.

Suitable diluents for carrying out the inventive

Connection variant (a) preferably inert organic solvents, in particular hydrocarbons, such as toluene, xylene, tetralin, hexane or cyclohexane, or ether. like tetrahydrofuran.

The reaction temperatures can be carried out when carrying out the inventive

Connection variant (a) can be varied over a wide range. In general, temperatures between 0 ° C and 200 ° C, preferably between 20 ° C and 150 ° C.

When carrying out the connection variant (a) according to the invention, per

Mol of compound of formula (Ia) generally between 1 and 3 mol, preferably between 1 and 2 mol of sulfurizing agent. The processing takes place according to usual methods.

Suitable oxidizing agents for carrying out the connection variant (b) according to the invention are all customary oxidizing agents which can be used for sulfur oxidation. Hydrogen peroxide, organic peracids such as peracetic acid, m-chloroperbenzoic acid, p-nitroperbenzoic acid or atmospheric oxygen are particularly suitable.

Inert organic solvents are also suitable as diluents for carrying out the connection variant (b) according to the invention. Hydrocarbons, such as gasoline, benzene, toluene, hexane or petroleum ether, are preferably used; chlorinated hydrocarbons, such as dichloromethane, 1, 2-dichloroethane. Chloroform, carbon tetrachloride or chlorobenzene; Ethers such as diethyl ether, dioxane or tetrahydrofuran; Carboxylic acids such as acetic acid or propionic acid. or dipolar aprotic solvents such as acetonitrile, acetone, ethyl acetate or dimethylformamide.

The connection variant (b) according to the invention can, if appropriate, be carried out in the presence of an acid binder. As such, all commonly used organic and inorganic acid binders come into question. Alkaline earth or alkali metal hydroxides, acetates or carbonates, such as calcium hydroxide, sodium hydroxide, sodium acetate or sodium carbonate, are preferably used.

If appropriate, the connection variant (b) according to the invention can be carried out in the presence of a suitable catalyst. All metal salt catalysts customarily used for such sulfur oxidations are suitable as such. Examples include ammonium molybdate and sodium tungstate.

The reaction temperatures can be varied over a wide range when carrying out the connection variant (b) according to the invention. In general, temperatures between -20 ° C and + 70 ° C, preferably at temperatures between 0 ° C and + 50 ° C.

To carry out the connection variant (b) according to the invention, 0.8 to 1.2 mol, preferably equimolar amounts, of oxidizing agent are generally used per mole of compound of the formula (Ib) if one wishes to interrupt the oxidation of the sulfur at the sulfoxide stage. For the oxidation to the sulfone one sets pro

Mol of compound of formula (Ib) in general 1.8 to 3.0 mol, preferably double molar amounts of oxidizing agent. The reaction, working up and isolation of the end products is carried out according to customary methods. The 5-amino-3- (thio) carbamoylpyrazoles of the formula (I) to be prepared by the process according to the invention are biologically active compounds, for example insecticides (cf., for example, DE 1 96 50 197 and WO 98/28 279).

Manufacturing examples

example 1

5-amino-3-carbamoyl-1 - (2,6-dichloro-4-trifluoromethylphenyl) pyrazole (1.0 g.

3.0 mmol) [Ex. (II-1)] and pyridinium p-toluenesulfonate (1.1 g, 4.5 mmol) in toluene (6 ml) are mixed with trifluoromethylsulfinyl chloride (0.6 g, 3.9 mmol). The mixture is heated at 50 ° C. for 18 hours, cooled, the reaction mixture is added, water (20 ml) is added and the mixture is extracted thoroughly with ethyl acetate. The combined organic extracts are washed with Na ₂ CO ₃ (aq.) And water, then with

Silica gel / activated carbon / MgS0 ₄ added and filtered. The filtrate is concentrated completely, the residue is dried in vacuo and 5-amino-3-carbamoyl-l- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfionylpyrazole (1.2 g, GC: 93.2 %, 81.9% of theory) as a light beige solid.

Manufacture of the starting product

5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole (6.4 g, 0.02 mol) are dissolved in dioxane (145 ml of water (120 ml). After adding K .CO- , (12.0 g, 0.09 mol) is added dropwise at 0 ° C with 30% -H ₂ O ₂ (27.5 ml, 0.27 mol), stirred for 2 hours at room temperature, the reaction solution is poured into water (500 ml) and extracted several times with ethyl acetate, the combined organic extracts are washed with Na ₂ HSO, (aq.), dried over Na ₂ SO ₄ , the solvent is distilled off and the residue is dried in vacuo.

5-Amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole (5.6 g, HPLC: 98.3%, 81.2% of theory) is obtained as a yellow solid.

Example 2

P ₄ S, ₀ (0.38 g. 0.85 mmol) and Na ₂ CO, (0.09 g, 0.85 mmol) are suspended in THF (20 ml) and stirred at room temperature until a yellow solution forms (about 30 minutes). 5-Amino-3-carbamoyl-1 - (2,6-dichloro-4-trifluoromethylphenyl) -4-tri_luoromethylsulfinylpyrazol (0.3 g, 0.65 mmol) [Ex. 1], stirred for 24 hours at room temperature, poured the reaction mixture into water, extracted with ethyl acetate, washed the organic extract with NaHCO ₃ (sat.), Dried over

Na ₂ SO ₄ and receives 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl) -3-thiocarbamoyl- 4- (tri_luoromethyl-sulfinyl) pyrazole after distilling off the solvent.

Claims

claims

1. Process for the preparation of 5-amino-3- (thio) carbamoylpyrazoles of

Formula (I)

in which

A stands for N or the grouping C-Hal ', where

Shark represents halogen,

X represents oxygen or sulfur,

Y stands for S, SO or SO ₂ and

R represents haloalkyl or alkyl,

characterized in that pyrazole derivatives of the formula (II)

in which

A, shark and X have the meaning given above,

with halides of the formula (III)

Hal "-Y-R (III)

in which

Shark "stands for halogen, especially chlorine or bromine, and

R and Y have the meaning given above,

if appropriate in the presence of a diluent and if appropriate in the presence of a reactant.

Process according to Claim 1, characterized in that the compounds of the formula (Ia) (X = O)

in which

A, Hai, Y and R have the meaning given in Claim 1,

subsequently reacted with a sulfurizing agent, if appropriate in the presence of a diluent.

Process according to Claim 1, characterized in that the compounds of the formula (Ib) (Y = S)

in which

A, shark, X and R have the meaning given in claim 1. subsequently oxidized with an oxidizing agent, optionally in the presence of a diluent and optionally in the presence of a catalyst.

4. The method according to any one of claims 1 to 3, characterized in that

A stands for N or the grouping C-Hal ', where

Shark represents fluorine or chlorine,

Shark stands for fluorine or chlorine, and

R represents (C _] -C ₄ ) haloalkyl with 1 to 9 identical or different

Halogen atoms from the series fluorine, chlorine and bromine or for (C _r C ₄ ) alkyl.

5. The method according to any one of claims 1 to 4, characterized in that

R represents one of the following radicals: -CF ₃ , -CHF ₂ , -CF ₂ CH ₃ , -CF ₂ CHF ₂ , -CF ₂ CHFC1, -CH ₂ CF ₃ , -CH ₂ -CF ₂ C1, -CH ₂ -CF ₂ CHF ₂ ,

-CF ₂ -CFC1-CF ₃ , -C (C1) (CF ₃ ) -CF ₂ C1, -C (C1) (CF ₃ ) -CHC1-CF ₃ , -CH ₃ , -C ₂ H ₅ .

Compounds of the formula (Ila)

in which

Shark and shark 'represents halogen, in particular fluorine or chlorine.