DE2537973C2 - - Google Patents

Description

The present invention relates to a method for manufacturing of 3-hydroxy-1,2,4-triazole derivatives of the formula I.

in which
R₁ is an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group with 3 to 8 carbon atoms,
R₂ is an alkyl group with 1 to 6 carbon atoms, a cycloalkyl group with 3 to 8 carbon atoms, an alkenyl group with 3 to 6 carbon atoms or a benzyl group optionally substituted by alkyl, alkoxy or alkylthio with 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro and
X oxygen or sulfur
means.

The 3-hydroxy-1,2,4-triazole derivatives of the formula I are valuable intermediates for the production of phosphoric acid esters, which as pesticides, in particular can be used as insecticides. Such phosphoric acid esters are, for example, in the German Offenlegungsschriften 22 59 960, 22 59 974 and 23 30 089.

It is known, 1,5-disubstituted 3-hydroxy-1,2,4-triazoles of the above Formula I by implementation of a by the radical R₁ according to above definition of substituted semicarbazide with orthoformic acid ester, subsequent chlorination of the initially obtained 3-hydroxy-1,2,4-triazole substituted in the 1-position in 5-position and exchange of the chlorine atom by the rest R₂-X-, where R₂ and X have the meaning given under formula I. have to manufacture. This known method does not need only a large number of reaction stages, but it is also capable not to be satisfied in terms of the yields achievable. The losses in yield essentially occur during implementation the chlorination of the intermediate 3-hydroxy-1,2,4-triazole and when replacing the imported chlorine with the Group R₂X- on.

It has now been found that the 3-hydroxy-1,2,4-triazole derivatives of formula I can produce in a simple manner, if to obtain a hydrazine carboxylic acid ester of the formula II

R₁-NH-NH-COOR (II)

in which R₁ has the meaning given under formula I. and R represents an alkyl radical with 1 to 4 carbon atoms, first with cyanogen chloride to the corresponding 2-substituted 2-cyanohydrazine carboxylic acid esters of the formula III

in which R₁ and R the specified under formula I and II Have meanings, implemented and then under alkaline Cyclized conditions in the presence of a compound R₂-X-H.

The inventive method is advantageous in one inert solvents performed. For the implementation of a Hydrazine carboxylic acid esters of formula II with cyanogen chloride halogenated hydrocarbons in particular as solvents, such as methylene chloride, chloroform, carbon tetrachloride, Chlorobenzene or aromatic hydrocarbons such as benzene and toluene, or ketones, in particular methyl ethyl ketone, or Esters, especially ethyl acetate, or ethers and ethereal ones Liquids such as diethyl ether, tetrahydrofuran and Suitable for dioxane. For the final cyclization reaction lower alcohols and water as solvents, where as lower alkanols those with 1 to 4 carbon atoms come into consideration.

The reaction of a hydrazine carboxylic acid ester of the formula II with Chlorine cyanide is in the presence of an alkali metal hydroxide, carbonate and in particular bicarbonate at temperatures between 0 and 30 ° C. It is  furthermore advantageous, the reaction of a hydrazine carboxylic acid ester of formula II with cyanogen chloride in a two-phase Reaction medium consisting of water and one of the above-mentioned water-immiscible solvents, perform.

The cyclization reaction is carried out at temperatures between 0 and 140 ° C, preferably at 40 to 80 ° C, performed. The reaction can be carried out at normal pressure or, if necessary, at overpressure up to 50 atm in an autoclave will. When performing the cyclization reaction in a lower alkanol one works in the presence of the corresponding sodium or potassium alcoholate. In the Carrying out the cyclization reaction in water works one in the presence of sodium or potassium hydroxide.

The radicals R₁ and R₂ include straight-chain as alkyl groups and branched alkyl radicals having 1 to 6 carbon atoms. The radicals R₁ and R₂ as cycloalkyl groups with 3 to 8 carbon atoms also include in the ring through lower alkyl groups substituted cycloalkyl radicals. You can also these cycloalkyl radicals via 1 to 3 methylene groups the nitrogen atom or be bound to X. The rest of R₂ as the benzyl group in the benzene nucleus by alkyl, alkoxy or alkylthio groups each having 1 to 4 carbon atoms, Halogen, especially chlorine or bromine, nitro, or trifluoromethyl Be substituted 1 to 2 times.

The method of the invention is illustrated by the following Examples explained in more detail:  

Example 1

73.0 g of 2-isopropylhydrazinecarboxylic acid ethyl ester and 42.0 g Sodium bicarbonate are in 200 ml of methylene chloride and 400 ml of water stirred in. After that, under constant Stir at room temperature for 20 minutes 30.8 g gaseous Chlorine cyanide initiated. After stirring for an hour the methylene chloride base is separated off over sodium sulfate dried and the solvent distilled off in vacuo. The residue was 75.0 g (87.5% of theory) of 2-isopropyl-2-cyanohydrazinecarboxylate as a colorless oil receive.

1370 g of ethyl 2-isopropyl-2-cyanohydrazinecarboxylate are placed in an autoclave and 423 g of methyl mercaptan pressed on. The temperature is maintained at 40 ° C for 24 hours. Then the resulting crystal slurry is poured into a 2.5 liter Transfer sulfonating flask and open in an oil bath for 2½ hours Heated to 120 ° C. The reaction mass cooled to 90 ° C then replaced with 1.2 liters of water, resulting in the reaction product deposits crystalline. The crude 1-isopropyl-5-methylthio-3-hydroxy-1,2,4-thiazole is filtered off and out recrystallized from one liter of acetonitrile. There will be 730 g (52% of theory) pure 1-isopropyl-5-methylthio-3-hydroxy-1,2,4-triazole obtained from the melting point 88-93 ° C.  

Example 2

In a solution of 800 g sodium hydroxide in 5000 ml water 960 g of methyl mercaptan are introduced and then 3024 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester dripped. The temperature rises during the dropping to 80 ° C and then held at 80 ° C for 2 hours. The mixture is then stirred at 20 ° C for 15 hours. To The addition of 1200 g of glacial acetic acid separates 2872 g of 1-isopropyl-5-methylthio-3-hydroxy-1,2,4-triazole from the melting point From 93-96 ° C. The filtrate is extracted with Ethyl acetate another 175 g of 1-isopropyl-5-methylthio-3-hydroxy-1,2,4-triazole won. The total yield is therefore 3047 g (87.5 of theory).  

Example 3

66.0 g of 2-ethylhydrazinecarboxylic acid ethyl ester and 42.0 g Sodium bicarbonate are in 200 ml of methylene chloride and 400 ml of water stirred in. After that, under constant Stir at room temperature for 20 minutes 30.8 g gaseous Chlorine cyanide initiated. After constant stirring the methylene chloride phase is separated off Dried sodium sulfate and the solvent in vacuo distilled off. 69.0 g (88% of the Theory) 2-ethyl-2-hydrazinecarboxylic acid ethyl ester obtained as a colorless oil.

In a solution of 4.6 g sodium in 150 ml absolute Ethanol at 60 ° C 31.4 g of 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester dropped in. Then the solution Boiled at reflux for 4 hours. From the cooled solution separates after adding 12 g of glacial acetic acid sodium acetate which is separated by filtration. The filtrate is evaporated to dryness in vacuo and the residue with Extracted 200 ml of chloroform. The extract will turn evaporated to dryness and the residue from cyclohexane recrystallized. There are 18.8 g (60% of theory) of 1-ethyl-5-ethoxy-3-hydroxy-1,2,4-triazole from the melting point Obtained 64 to 67 ° C.  

Example 4

In a solution of 40 g sodium hydroxide in 300 ml water 48 g of methyl mercaptan are introduced and then 185 g of 2-sec-butyl-2-cyanohydrazinecarboxylic acid ethyl ester dripped. The temperature rises during the dropping to 90 ° C. Then allowed to cool to room temperature. After adding 60 g of glacial acetic acid, 148.9 g (79.5% of theory) 1-sec-butyl-5-methylthio-3-hydroxy-1,2,4-triazole from the melting point 104-106 ° C.

The 2-sec-butyl-2-cyanohydrazinecarboxylic acid ethyl ester used as the starting material becomes analogous to that in examples 1 and 3 specified methods by reacting ethyl 2-sec-butylhydrazinecarboxylate made with cyanogen chloride.  

Example 5

In one of 361 g sodium and 9 liters absolute ethanol prepared ethanolic solution of sodium ethylate 905 g of methyl mercaptan were initially introduced and then 2470 g of ethyl 2-ethyl-2-cyanohydrazinecarboxylate were added. The solution obtained is first 15 hours at room temperature and then held at reflux temperature (80 ° C) for 3 hours. After adding 942 g of glacial acetic acid falls from the cooled Solution from sodium acetate, which is separated by filtration. The filtrate is evaporated to dryness in vacuo, the residue taken up in 7 liters of chloroform and filtered off. The The filtrate is evaporated at normal pressure and toluene is added. filtered and 1 liter of cyclohexane was added to the filtrate. There are 1890 g (75.5% of theory) of 1-ethyl-5-methylthio-3-hydroxy-1,2,4-triazole obtained from the melting point 83-87 ° C.  

Example 6

In one of 4.6 g sodium and 100 ml absolute ethanol prepared ethanolic solution of sodium ethylate first 14.9 g of ethyl mercaptan and then 31.4 g 2-ethyl-2-cyanohydrazinecarboxylic acid ethyl ester. It a crystalline precipitate forms that lasts 3 hours Reflux is cooked. The cooled suspension is after the addition of 12 g of glacial acetic acid by filtration from the precipitated Sodium acetate freed and the filtrate evaporated to dryness in vacuo. The residue is mixed with 200 ml of chloroform and filtered off. The filtrate is again evaporated to dryness. The residue is recrystallized from cyclohexane. There are 26 g (75% of theory) of 1-ethyl-5-ethylthio-3-hydroxy-1,2,4-triazole obtained from the melting point 65-68 ° C.  

Example 7

In a solution of 33.2 g sodium hydroxide in 190 ml water are initially 51.5 g of ethyl mercaptan at room temperature and then 163 g of ethyl 2-cyclopentyl-2-cyanohydrazinecarboxylate drips. Then the solution is 1 hour Reflux cooked. The cooled solution separates after adding 50 g of glacial acetic acid, 167 g (94% of theory) 1-Cyclopentyl-5-methylthio-3-hydroxy-1,2,4-triazole from Melting point from 93-95 ° C.

The 2-cyclopentyl-2-cyanohydrazinecarboxylic acid ethyl ester used as starting material becomes analogous to that in examples 1 and 3 described method prepared by reacting ethyl 2-cyclopentylhydrazinecarboxylate with cyanogen chloride.  

Example 8

To a solution of 132 g sodium hydroxide in 750 ml water 244 g of allyl mercaptan are given and then at Room temperature 514 g of ethyl 2-ethyl-2-cyanohydrazinecarboxylate dripped. After refluxing for one hour 198 g of glacial acetic acid are added to the cooled solution. The oily phase is separated off and dried to dryness in vacuo evaporated. There are 260 g (43% of theory) of 1-ethyl-5-allylthio-3-hydroxy-1,2,4-triazole with a melting point of 74-76 ° C. receive.  

Example 9

A solution of 8 g sodium hydroxide in 100 ml water and 50 ml of alcohol are initially 31.7 g of 4-chlorobenzyl mercaptan added and then 34.2 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester dripped. During the dropping the temperature rises to 38 ° C. Then it is at 85 ° C for 2 hours held. After cooling to 20 ° C, 12 g of glacial acetic acid added dropwise, with a white crystals of 1-isopropyl-3-hydroxy-5- (4-chlorobenzylthio) -1,2,4-triazole separates. This is recrystallized in 400 ml of methanol and gives 42 g product of mp 140-141 ° C. (74% of theory).  

Example 10

In a solution of 8 g sodium hydroxide in 100 ml water and 50 ml of alcohol are first 24.8 g of benzyl mercaptan given and then 34.2 g of 2-isopropyl-2-cyanohydrazinecarboxylic acid ethyl ester dripped. During the dropping the temperature rises to 38 ° C. Then 2 hours on Kept at 85 ° C. After cooling to 20 ° C, 12 g Glacial acetic acid was added dropwise, forming a white crystal from 31 g of 1-isopropyl-3-hydroxy-5-benzylthio-1,2,4-triazole separates from mp. 134-135 ° C. (62% of theory).  

Example 11

In one by dissolving 11.5 g of sodium in 300 ml absolute ethanol made solution of sodium ethylate 24.05 g of methyl mercaptan are introduced. Then be at 60 ° C 71.5 g of 2-cyano-2-methyl-hydrazine carboxylic acid ester added dropwise, the temperature rising to 75 ° C. To when the addition is complete, the reaction mixture is kept under for 5 hours Reflux cooked. Then be in the room temperature cooled solution 30 g of glacial acetic acid were added dropwise. After separation of the resulting precipitate by Filtration removes the filtrate from the solvent in vacuo exempted. The residue is made from 140 ml with dry ice cooling Recrystallized methanol. There are 21.8 g of 1-methyl-5-methylthio-3-hydroxy-1,2,4-triazole (30% of theory) from Melting point 128-130 ° C obtained.

The ethyl 2-cyano-2-methylhydrazinecarboxylate required as the starting material becomes analogous to that in Examples 1 and 3 described method by reacting ethyl 2-methylhydrazinecarboxylate made with cyanogen chloride.

Claims (1)

Process for the preparation of 3-hydroxy-1,2,4-triazole derivatives of the formula I. in which
R₁ is an alkyl group with 1 to 6 carbon atoms or a cycloalkyl group with 3 to 8 carbon atoms,
R₂ is an alkyl group with 1 to 6 carbon atoms, a cycloalkyl group with 3 to 8 carbon atoms, an alkenyl group with 3 to 6 carbon atoms, or one optionally by alkyl, alkoxy or alkylthio with 1 to 4 carbon atoms, halogen, trifluoromethyl or nitro 1- to 2-fold substituted benzyl group and
X represents oxygen or sulfur,
characterized in that a hydrazine carboxylic acid ester of the formula IIR₁-NH-NH-COOR (II) in which R₁ has the meaning given under formula I and R is an alkyl radical having 1 to 4 carbon atoms, first at 0-30 ° C in the presence of a Alkali metal hydroxides, carbonates or hydrogen carbonates with cyanogen chloride to the corresponding 2-substituted 2-cyanohydrazine carboxylic acid ester of the formula III in which R₁ and R have the meanings given under formulas I and II, and then reacted in a lower alkanol in the presence of the corresponding sodium or potassium alcoholate, or in water in the presence of sodium hydroxide or potassium hydroxide at a temperature between 0 and 140 ° C. cyclized in the presence of a compound R₂XH.