DE3114316A1 - Process for the preparation of 3-hydroxy-1,2,4-triazoles - Google Patents

Abstract

Preparation of (substituted) 3-hydroxy-1,2,4-triazoles by reacting phenylhydrazines with urea or cyanates and cyclisation of the resulting semicarbazides by means of formic acid in a one-pot reaction with addition of a strong acid.

Description

Process for the preparation of 3-hydroxy, 2, L1-triazoles

3-hydroxy-1,2-triazoles of the general formula I, where R = (C1-C4) -alkyl, halogen, (C1-C4) -alkoxy, trifluoromethyl, cyano, Mitro or (C1-C4) -alkoxyearbonyl and n = 0, 1, 2 or 3 are used as intermediates for Manufacture of pesticides. used in particular by insecticidal and acaricidal phosphoric acid esters (cf. DE-PS 910 652 and DE-PS 1 670 876). To date, they have been produced in a two-stage reaction by converting an optionally substituted phenylhydrazine into the corresponding phenyl semicarbazide and isolating it and further reacting it with formic acid or a formic acid derivative to give (I).

The phenylsermicarbazide can be obtained by reacting the phenylhydrazine hydrochloride or acetate with potassium cyanate in water (Ann. 190, 113; Ber. 26, 2613) or by Conversion of free phenylhydrazine or its hydrochloride with urea (Gazz. chim. Ital. 16, 202; Ber. 20, 2359).

It is then isolated from the resulting crude product, if appropriate in a solvent, with formic acid (Ber. 26, 2612) or orthoformic acid esters (DE-AS 2 251 074) converted to (I), the yields in both stages being 50% of theory. Do not exceed th. In addition to the moderate yields, these process methods show a number of other shortcomings. In particular, do all of the previously described procedure the isolation and purification of the phenyl semicarbazide obtained first is required. Since the phenylhydrazine does not react quantitatively, the Phenylsemicarbazids unconsumed phenylhydrazine into the sewage. The latter is known as a blood poison for warm-blooded animals and still in concentrations of 0.001% highly toxic to fish.

Because of its bactericidal properties, it is also difficult biodegradable. The removal of phenylhydrazine from wastewater except for harmless concessions is therefore only possible in a very laborious way.

The subject of the present report is now a process: for production of optionally substituted 3-hydroxy-1,2,4-triazoles by reacting optionally substituted phenylhydrazines with urea or alkali or

Ammonium cyanate and further conversion of the phenyl semicarbazides obtained with formic acid in the second stage, which is characterized in that the two reaction stages in a one-pot reaction with the addition of an inorganic one or organic acid or an anhydride or halide thereof in the second Carries out reaction stage.

According to the invention, the phenylhydrazine is initially either with an at least equimolar amount, preferably with a slight excess of up to 15 mol%, of a cyanate salt (NaOCN, KOCN, NH40CN) in the presence of a approximately equimolar amount of an organic or inorganic acid at temperatures from 0 ° C to 60 ° C or with an at least equimolar amount, preferably one Excess of up to 40 mol d, urea in the presence of about 0.001-1.35 mol, is preferred 0.1-1.35 mol, based on the phenylhydrazine of the formula II used, of an organic or inorganic acid or its ammonium salt at a temperature of from 1000C to 1600C, preferably white 105 - 1400C, in a suitable solvent, ge; Ebenenl'al.ls under pressure, converts to the corresponding semicarbazide.

The use of organic or organic acids is preferred Hydrochloric acid, hydrogen chloride gas, sulfuric acid, phosphoric acid or toluenesulfonic acid. The ammonium salt used is preferably ammonium chloride, ammonium sulfate or ammonium formate .

The solvent used is water or organic inert solvents which is advantageous - if you do not want to work under pressure - above 1000C, preferably boil at 115 - 1400C 0, such as toluene, xylene, chlorobenzene, o-dichlorobenzene cumene as well as higher-boiling paraffins. You can also use a water / organic mixture Solvent work.

The amount of solvent can and can be varied within wide limits for example two to ten times, preferably three to five times Weight of the phet1ylhydrazine used. The acid required can in concentrated form in aqueous solution, in the case of the hydrohalic acids can also be used as a gas. When using a phenylhydrazine salt is a No need to add acid. When using technical, hydrous phenylhydrazine or one of its hydrous salts or an aqueous solution of those used Acid and use of an inert organic solvent or diluent the water can azeotropically with the solvent used as the reaction medium distilled off and then the solution to the reaction temperature given above be heated further. The ammonia formed during the reaction can, as far as it is is not bound by the acid present as ammonium salt, collected in water and other technical uses. The response time is In the first process stage generally two to six hours.

After completion of the semicarbazide formation, a temperature temperature from 80 - 90 ° C the resulting suspension of the semicarbazide with at least the stoichiometric Amount, but preferably with 2 to 3 moles of formic acid per mole of semicarbazide and 0.05-0.5 mol, preferably 0.1-0.3 mol of an inorganic or strong organic Acid or an anhydride or halide of the same and at temperatures heated from 80 to 140 ° C, preferably 90-1000C. The response time is between 2 and 24 hours.

The same acids come into consideration as for the first process stage, suitable as acid halides are the chlorides and bromides of inorganic acids such as Tionyl chloride, sulfuryl chloride, phosphorus trichloride and bromide, phosphorus pentachloride and phosphorus oxychloride. A particularly suitable acid anhydride is phosphorus pentoxide.

The 3-hydroxy-1,2,4-triaol thus obtained in suspension is after cooling sucked off to room temperature and rinsed with water, when using organic solvents or diluents, optionally with alcohol and water, free of salts and acids washed and obtained practically pure after dryness.

The process according to the invention gives 3-hydroxy-1,2-triazoles of the formula wherein R is a substituted or unsubstituted ii'phatic, cycloaliphatic or aromatic radical. The following meanings may be mentioned, for example: (C1-C8) -alkyl, (C1-C) -alkoxy- (C1-C) -alkyl, cyano- (C1-C4) -alkyl, halogen- (C? Cq) -alkyl, (C3-C7) -cycloalkyl optionally by one or two substituents from the group (C1-C) -alkyl, (C1-C4) -alkoxy, (C1-Cq) -alkylthio, halogen, trifluoromethyl, cyano, nitro and (C1 -C4) -Alkoxyearbonyl sud ..

substituted (C6-C10) -aryl and optionally by one or two substituents benzyl substituted from the group (C1-C4) -alkyl, (C1-C4) -alkoxy, halogen and nitro.

The claimed method shows compared to the previously described and carried out manufacturing methods for 3-hydroxy-1,2,4-triazoles the following improvements: This makes it unnecessary to summarize the previously separate process steps the previously required cleaning and drying operations for the in semicarbazide produced in the first stage. This causes losses of semicarbazide avoided and the overall yield compared to the known procedures by 10 up to 15% increased.

The phenylhydrazine not converted in the first manufacturing phase remains in the reaction mixture and becomes in the second phase with the formic acid Compounds implemented in the separation of the triazole in the solvent mixture remain.

You can use organic solvents and thinners these are recovered by working up by distillation. When using This is initially water with a water-immiscible organic solvent extracted, which is recovered by distillation after separation. The one in both Any distillation residue that arises can be incinerated without damaging the environment. As a result, the wastewater that only arises after the second stage is now free of Phenylhydrazine and can now be biologically cleaned.

When using substoichiometric amounts of acid in the first phase The process can also reduce the salt pollution of the wastewater to a minimum will.

The procedure is further illustrated by the examples given below explained and documented.

PROCEDURE EXAMPLES Example 1 1-Phenyl-3-hydroxy-1,2,4-triazole 225 g (2 mol) phenylhydrazine technically 96%, 221.2 g (2 mol) 33% hydrochloric acid, 120 g (2 mol) of urea and 800 ml of water are taken for 5 hours with the vessel closed heated to 125 - 12800. This creates a pressure of 2.6 - 2.8 at.

It is then cooled to 1000C and poured over a dropping funnel 324.7 g (6 mol) of 85% formic acid and 50 g (0.5 mol) of concentrated sulfuric acid added, then stirred for 6 hours at 950C, cooled and the precipitated I-phenyl-3-hydroxy-1,2,4-triazole suction filtered.

(After adding 144 g of methanol (4.5 mol) from the mother liquor the excess formic acid was recovered as methyl formate by distilling off (column 320C) will).

The filter cake is abundantly washed with water, finally 1-Phenyl-3-hydroxytriazole dried in a vacuum drying cabinet at 1000C. You get 238.3 g (74% of theory) of melting point 280-282 ° C.

Example 2 1-phenyl-3-hydroxy-1,2,4-triazole 108 g (1 mol) phenylhydrazine, 60 g (1 mol) of urea are placed in 500 ml of xylene; then one gives under vigorous stirring to 111 g (1 mol) of concentrated hydrochloric acid. Circling water A water separator is then used to heat to 13500 and the reaction mixture Leave at this temperature for 2.5 hours.

After cooling to 90 ° C., 135.2 g (1 mole) of 85% strength are first added Formic acid, then 25 g (0.25 mol) concentrated Sulfuric acid too and heated at 9500 for a further 6 hours.

After cooling, the end product is filtered off, thoroughly with water Washed acid-free and dried in a drying cabinet under vacuum at 1000C. Man receives 124.6 g (77.5% of theory) 1-phenyl-3-hydroxy-1,2,4-triazole with melting point 281-2820C.

Example 3 1-phenyl-3-hydroxy-1,2,4-triazole 108 g (1 mol) phenylhydrazine, 60 g (1 mol) of urea and 300 ml of xylene are in an enamelled autoclave submitted. Then 5.5 g (0.15 mol) of hydrogen chloride are added with thorough stirring pressed over the surface of the liquid and heated to 1350C after relaxation and stirred at this temperature for 4 hours. The resulting ammonia is diverted and neutralized in hydrochloric acid.

After cooling to 90 ° C., 135.2 g (2.5 mol) of 85% formic acid are obtained and 25 g (0.25 mol) of concentrated sulfuric acid are added and the reaction mixture Stirred at 9500 for 6 hours. After cooling to room temperature, the end product is filtered off, washed acid-free with plenty of water and dried in vacuo at 1000C. 130.7 g (81.2% of theory) are obtained

Th.) 1-Phenyl-1-hydroxy-1,2,4-triazole with the melting point 280-283 ° C.

Example 4 1-Phenyl-3-hydroxy-1,2,4-triazole 111.5 g (1 mole) phenylhydrazine technically 96 -ig, 84 g (1.4 mol) urea, 71.5 g (1.33 mol) ammonium chloride and 250 ml of water until the ammonia development has ended (5 hours) bti 105 - 1060C heated. After cooling to 95 ° C., 135.2 g (2.5 mol) of 85% formic acid are obtained and 33 g (0.3 mol) of concentrated hydrochloric acid were added.

The reaction mixture is stirred for 8 hours at this temperature, it is then cooled and the 1-phenyl-1,2,4-triazole precipitate is filtered off with suction, with a lot of water washed neutral and dried. 115.9 is obtained g (72 9b of theory) of product with a melting point of 283-2840C.

Example 5 1-Phenyl-3-hydroxy-1,2,4-riazole 111.5 g (1 mole) phenylhydrazine 96% strength, 68 g of ammonium formate and 66 g (1.1 mol) of urea are dissolved in 250 ml of H20 Stirred for 8 hours at 105.degree. C., then 97.4 g (1.8 mol) of 85 8 ige are obtained at 95.degree Formic acid and 75 g concentrated sulfuric acid were added and 6 hours at 950C stirred. The suspension of 1-phenyl-3-hydroxy-1,2,4-triazole is after cooling Sucked off, washed acid-free with water and dried. 103 g (64% d.Th.) 1-phenyl-3-hydroxy-1,2,4-triazole with the melting point; 279 0C.

Example 6 1-Phenyl-3-hydroxy-1,2,4-triazole 44.3 ml (0.5 mol) concentrated Hydrochloric acid are placed in 270 ml of water and 54 g (0.5 mol) with thorough stirring Phenylhydrazine is metered in, then at 200C-300C a solution of 43.5 g (0.537 mol) of potassium cyanate in 95 ml of water were added dropwise and the mixture was stirred for 1 hour.

The aqueous suspension of 1-phenylsemicarbazide is 69 g (1.5 Mol) formic acid and 12.5 g (0.125 mol) of concentrated sulfuric acid are added and Heated at 95 ° C. for 6 hours. After cooling, the solid is filtered off with suction with water washed and dried in vacuo. 71.6 g (89% of theory) of 1-phenyl-3-hydroxy-1,2'4-uriazoi are obtained with a melting point of 2830C.

Claims (3)

Claims: 1. Process for the production of optionally substitute values 3-hydroxy-1,2,4-triazoles by reacting optionally substituted phenylhydrazine (salt) with urea or alkali or ammonium cyanate and ring closure of the semicarbazide obtained by means of formic acid, characterized in that the two reaction stages in a one-pot reaction with the addition of an inorganic or strong organic Acid or a halide or anhydride thereof in the second reaction stage performs. 2. The method according to claim 1, characterized. that one as inorganic or strong organic acid hydrochloric acid, hydrogen chloride gas, phosphoric acid, Sulfuric acid or p-toluenesulfonic acid is used. 3. The method according to claim 1 or 2, characterized in that the Amount of acid is 0.05-0.5, preferably 0.1-0.3 mol per mol of semicarbazide.