KR800001162B1 - Process for the preparation of 5-amino-1,2,3-thiazole - Google Patents

Abstract

Title compd. (I) useful as herbicide intermediate was prepd. 4 steps. (1) XCH2CH:O(X = halogen) or its acetal reacted with H2N-NH-COR(R = alkoxy, amino or alkylamino) to give XCH2CH:NNHCOR(II) (2) II reacted with SOCl2 to give 5-halogeno-1,2,3-thiadiazole(III) (3) III reacted with NH3 to give I. ClCH2CH:NNHCOEt was prepd. by the reaction of chloroacetalaldehyde and H2NNHCOEt. II and SOCl reacted to give 5-chloro-1,2,3-thiadiazole followed by reaction with conc. NH3 give I.

Description

Method for preparing 5-amino-1,2,3-thiadiazole

The present invention relates to a process for preparing 5-amino-1,2,3-thiadiazole, of the following structural formula (I).

Two methods of preparing 5-amino-1,2,3-thiadiazole are known.

One method of preparation is the reaction of diazomethane with acyl-mustard oil. (See J. Goerdeler and G. Gnad, Ber, 99, 1618, 1966)

However, diazomethane is explosive and toxic, and its yield is very low, about 32%, which makes it unsuitable for industrial production of 5-amino-1,2,3-thiadiazole.

Another method of preparation is the introduction of an amino group to thiadiazoling in the form of a successive seven-step reaction, the so-called Gabriel synthesis method, an amino protecting group (phthalamido group) (see DL Pain and R. Slack, J. Chem. Soc. 5166-76, 1965).

However, this process requires a seven-step reaction, which is very expensive and yields very low (about 35%), and the phthalic acid hydrazide produced in this process cannot be regenerated, requires large amounts and requires high energy. Therefore, it is not suitable for industrial production of 5-amino-1,2,3-thiadiazole.

Therefore, the main object of the present invention is to reduce the production process, increase the yield and improve the production process suitable for industrial production of the material in only 2-3 steps of 5-amino-1,2,3-thiadiazole. have.

Accordingly, the present invention is obtained by reacting a halogen-acetaldehyde of the following structural formula (II) or its acetal with a hydrazine derivative of the following structural formula (III) in a mixture with a water-soluble solvent or an organic solvent, preferably in the presence of a mineral, if necessary. The acyl-hydrazone of the following structural formula (IV) is reacted with thionyl chloride of the following structural formula (V) to obtain 5-halogeno-1,2,3-thiadiazole, which is the following structural formula (VI). VI) The compound is dissolved in an organic solvent, if necessary, and reacted with ammonia in the presence of a catalyst, preferably a mineral acid or a Lewis acid, to prepare 5-amino-1,2,3-thiadiazole of the above formula (I). It is about a method.

In the above structural formula

X is a halogen atom

R is an alkoxy group, an amino group or an alkylamino group.

It is preferable that the alkoxy group and alkylamino group represented by R contain C1-C4, respectively.

The convenient points when reacting according to the present production method are as follows;

(a) the reaction of the halogen-acetaldehyde of formula (II) with the hydrazine derivative of formula (III) is carried out in the range of -20 ° -50 ° C, preferably 0 ° -20 ° C.

(b) the reaction of acyl-hydrazone having the structural formula (IV) with thionyl chloride of the structural formula (V) is carried out in the range of -20 ° -100 ° C, preferably -5 ° -50 ° C.

(c) the reaction of 5-halogento-1,2,3-thiadiazole of the structural formula (VI) with ammonia is 1-10 atm, preferably 1 atm, in the range of -70 ° -120 ° C. Is performed.

The preparation method according to the present invention can be explained by the following scheme;

This production method utilizes for the first time a 1,2,3-thiadiazole system primarily produced and the introduction of an ano functional groups with ammonia instead of halogen atoms.

In this production process only three stages of synthesis are required, starting with the inexpensive primary compound. This is a very big advantage.

The production process of the present invention, with two to three steps of manufacturing process, the use of useful primary materials and the relaxed conditions of synthesis, is a novel method with experimental characteristics that can hardly be surpassed.

Moreover, yields are surprisingly high. That is, the second stage is obtained with a relatively high yield of about 65% or more, and the first and third stages are almost quantitative, and the total yield is about 50-60% throughout the entire stage.

Synthesis of the acyl-hydrazone having the structural formula (IV) is carried out by reaction with the hydrazine derivative of the structural formula (III) in a water-soluble solvent with halogen-acetaldehyde of the structural formula (II) as a starting material. Halogen-acetaldehyde is preferably used in the form of its aqueous solution. For example, the hydrazine composition is added dropwise to the aldehyde solution diluted in diluted form or solvent, for example, water or alcohol having 1-4 carbon atoms and diluted in water or alcohol. The addition of the reaction liquid can also be made under reversible conditions. The reaction is carried out at -20 ° -50 ° C, preferably at -0 ° -20 ° C.

After the reaction, the solid reaction product can be separated into a colorless crystalline phase by filtration, freezing or solvent removal. It can be recrystallized with suitable organic solvents such as ketones, alcohols, nitriles, esters and combusted hydrocarbons such as acetone, acetonitrile, methanol, ethanol, ethyl acetate or chloroform and are also stable at room temperature. However, the material can generally be reacted further in the dry state without recrystallization.

Filtering the halogen-acetaldehyde diluent with celite can increase the purity of the reaction product.

Acyl-hydrazone of the above formula (IV) may also be produced from the corresponding halogen-acetaldehyde acetals.

The compound of formula IV is acetal, if necessary, mixed with an organic solvent, such as alcohol or ether (such as methanol, ethanol or tetrahydrofuran), injected into a water-soluble solvent and added to a mineral acid such as sulfuric acid or hydrochloric acid. The decomposition of acetal takes place in a short time at -0 ° -100 ° C, usually at the boiling point of the solvent. After boiling for 15 minutes, the reaction mixture is cooled to room temperature, and the hydrazine composition is diluted with an undiluted form or a solvent and added thereto. The addition of the reaction liquid can also be made under reversible conditions.

The acyl-hydrazone of the above formula (IV) is then reacted with thionyl chloride to form 5-halogeno-1,2,3-thiadiazole of the above formula (VI). The reaction is carried out at -20 ° -100 ° C, preferably at -5 ° -50 ° C.

The reaction time may be 1 hour-20 hours depending on the reaction temperature.

To synthesize 5-halogeno-1,2,3-thiadiazole, the reaction composition is used in approximately equimolar amounts. However, thionyl chloride can be used in large excess as a solvent.

However, it is advantageous to use acyl-hydrazone and thionylchloride in a ratio of 1: 3.

The reaction can also be carried out in the presence of a solvent that is inert to the reaction solution. Chlorinated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride and aliphatic and aromatic hydrocarbons such as petroleum ether, pentane, cyclohexane, benzene, toluene and xylene and ethers, such as diethyl ether, tetrahydrofuran, dioxane, ethylene glycol Lycol diethyl ether and diethylene glycol diethyl ether and esters such as ethyl acetate.

As a rule, acyl-hydrazone, also dissolved or also suspended in an appropriate solvent, is optionally added dropwise to thionylchloride optionally diluted in an organic solvent. However, addition of the reaction liquid can be made under reversible conditions.

Hydrogen chloride formed during the reaction can be continuously removed from the reaction vessel using a conventional inert gas.

The reaction mixture is then treated according to known methods.

The solvent and excess thionyl chloride can be removed by steam distillation and the residue can be fractionally distilled. In addition, the excess thionyl chloride may be decomposed into saturated sodium bicarbonate solution, sodium carbonate or potassium carbonate solution, sodium acetate solution or sodium hydroxide or potassium hydroxide solution or water directly, and then the reaction solution may be steam distilled. 5-halogeno-1,2,3-thiadiazole is very specific and can be easily removed from the steam concentrate. The aqueous phase can be further extracted with pentane, ether or methylene chloride.

The reaction product is obtained in a slightly yellow liquid phase when steam distillation, and when fractional distillation, a reaction product is obtained as a colorless and highly volatile liquid phase. This liquid has the property of solidifying in crystalline form in the condenser.

Reaction products are readily soluble in organic solvents such as hydrocarbons, halogenated hydrocarbons, ethers, ketones, alcohols, esters, carboxylic acid amides, and nitric acid carboxylic acids, and are insoluble in water.

For further reaction, there is no need to purify the crude product obtained by steam distillation. The reaction product obtained has the property of being easily blackened by sunlight depending on the purity. However, even after long storage, there is almost no loss of content.

5-halogeno-1,2,3-thiadiazole is then reacted with ammonia to obtain 5-amino-1,2,3-thiadiazole, which is the above formula (I). Ammonia may be used in the form of absorbing ammonia in an organic solvent such as methanol, ethanol, benzene, toluene, xylene, tetrahydrofuran or dioxane. However, it is more practical to use it in liquid phase. The reaction is carried out at -70 ° -120 ° C, preferably at the reflux temperature of the reaction mixture. The pressure is 1-10 atm, preferably 1 atm. The reaction composition can be reacted in the same amount but it is more advantageous to use an excess of ammonia, preferably 1-20 equivalents.

The reaction can be carried out according to an addition-removal reaction catalyzed by an acid or Lewis acid. Lewis acids include mercuric chloride, sulfuric ammonium chloride, ammonium chloride, ammonium bromide, mercury bromide, (CH ₃ ) ₃ SiOSO ₂ CF ₃ , stannic chloride, BF ₃ and para-toluene sulfonic acid hydrate.

The production method is advantageous in which the halogen composition is injected into liquid ammonia at atmospheric pressure at -60 °-(-) 35 ° C. and continuously reacted at reflux for 1-8 hours.

In general, ammonium salts produced during the reaction catalyze the exchange of chlorine. At the end of the reaction, ammonia is evaporated and 5-amino-1,2,3-thiadiazole formed is separated from the ammonium salt by thorough extraction with a suitable organic solvent such as ethyl acetate, methylene chloride, acetone, methanol or ethanol or Or directly recrystallized from water.

By the above method, 5-amino-1,2,3-thiadiazole is obtained in an extremely pure form and in almost quantitative yield. Therefore, it is no longer necessary to purify to further react. The 5-amino-1,2,3-thiadiazole obtained can be modified with its derivatives, such as 1,2,3-thiadiazole-urea.

The following examples illustrate the invention.

Example 1

[(a) Preparation of 2-chloroethylideneaminocarbamic acid ethyl ester]

550 g (3.5 moles) of 50% strength chloracetaldehyde aqueous solution is diluted in 3,000 ml of water, and 10 g of Celite 545 is added thereto to bind the separated resin. Three bent tubes with stirrer and thermometer were filtered through a 6 L round bottom flask with the filter paper. While cooling with ice, a solution of 364 g (3.5 mol) of hydrazinoformate ethyl ester dissolved in 360 ml of water was added dropwise while stirring for 15 minutes. The internal temperature is maintained at 0 ° -5 ° C. At this point, a viscous white crystalline magma is formed immediately. The mixture is stirred for a further 30 minutes at room temperature, the crystals are filtered off with suction and washed with about 6 liters of water until neutral and dried under vacuum at 30 ° C. until content is reached.

Yield: 525.98 g = 91.3% of theory

Melting Point: 120-121 ℃ (Recrystallized from Alcohol Hole)

Elemental analysis

Calculated Value: C, 36.48% H, 5.51% Cl, 21.54% N, 17.02%

Found: C, 36.91% H, 5.46% Cl, 21.37% N, 16.93%

[(b) 2-chloroethylideneamino carbamic acid ethyl ester]

To a 250 ml bent tube equipped with a stirrer, a thermometer and a reflux condenser, 60 ml of water and 0.8 ml of concentrated hydrochloric acid were added to a round bottom flask and heated to 90 ° C., followed by 15.2 g of chloroacetaldehyde diethylacetal. The whole solution was stirred at 90 ° -100 ° C. for 15 minutes, cooled to 30 ° C., and a solution of 12.5 g of hydrazinoformate ethyl ester dissolved in 40 ml of water was added dropwise for 10 minutes. At this point, white crystalline magma is formed. After stirring for 15 minutes, the magma is suction filtered, washed with 30 ml of ice-water, and dried under vacuum at room temperature until a constant weight to obtain a white crystalline substance.

Yield: 14.4 g = 87.5% of theory

Melting Point: 120-121 ℃

The following compounds can be prepared according to similar methods;

Example 2

[Preparation of 5-chloro-1,2,3-thiadiazole]

Three bent tubes equipped with a stirrer, thermometer, reflux condenser and gas ejector were added 110 ml (1.5 mol) of thionyl chloride to a 2 liter round bottom flask, cooled to 5 ° C and 2-chloroethylideneaminocarbamic acid ethyl ester 82.3 g is added over 5 minutes. Since the internal temperature rises to 20 ° C., the mixed solution is stirred in an ice bath for 15 minutes and then stirred at room temperature for 2 hours. A dark green reaction solution forms with the release of the gas. After stirring for 15 minutes at room temperature, 600 ml of sodium bicarbonate saturated solution was added to the resulting brown reaction solution and slowly decomposed at an internal temperature of 5 ° -20 ° C. Thereafter, steam distillation is performed to collect 1 liter of distillate. Chlorthiadiazole is separated into a yellow liquid. After separation, the distillate is extracted twice with 200 ml of pentane. The crude product extracted with pentane extract is dried over magnesium sulfate and evaporated to 40 ° C. under vacuum.

Yield: 46.0 g (crude to be used in the next step without distillation)

Distillation of the crude product yields 5-chloro-1,2,3-thiadiazole having a bp ₃₀ of 58-62 ° C. (melting point: about 20 ° C.).

Yield: 39.1 g (65.1% of theory)

Elemental analysis

Calculated Value: C, 19.92% H, 0.84% Cl, 29.41% N, 23.24%

Found: C, 20.14% H, 1.01% Cl, 31.00% N, 23.22%

According to a similar method, 5-bromo-1,2,3-thiadiazole can be prepared having a bp ₃₀ of 61-64 ° C.

Example 3

[Preparation of 5-amino-1,2,3-thiadiazole]

Three bent tubes equipped with a dry ice cooler, magnetic stirrer and a dry ice / methanol cooling bath with a temperature of -75 ° C were added 200 ml of ammonia to a 1 liter round bottom flask, and 5- 50 g (0.415 mol) of chloro-1,2,3-thiadiazole are added. Yellow crystals separate immediately. The mixture is stirred for 3 hours while refluxing without using a cooling solution. After about 1 hour of reaction, an almost clear yellow solution is formed. The ammonia is then evaporated off at room temperature for 2 hours 30 minutes.

The mixture is then dried for 30 minutes under reduced pressure using a water jet pump to completely remove the ammonia. The remaining residue in the flask was immersed several times with 900 ml of ethyl acetate while stirring and boiling. The ethyl acetate solution is evaporated to dryness at 40 ° C. under vacuum.

Yield: 36.1 g (85.9% of theory)

Melting Point: 137-138 ℃

The evaporated dried material is dissolved in acetone to form a clear solution.

The product obtained by the production method described in the above examples can be used in the preparation of plant protection agents and pesticides, for example the preparation of 1,2,3-thiadiazole-urea effective as a herbicide.

Claims (1)

By reacting halogen-acetaldehyde of formula (II) or acetal thereof and hydrazine derivative of formula (III), acyl-hydrazone of formula (IV) is reacted with thionyl chloride of formula (V) To prepare 5-halogeno-1,2,3-thiadiazole, which is the following structural formula (VI), and to react the 5-halogeno-1,2,3-thiadiazole obtained with ammonia (I) Production method of 5-amino-1,2,3-thiadiazole

Wherein X is a halogen atom and R is an alkoxy group, an amino group or an alkylamino group.