CS198248B2 - Process for preparing 1-phenyl-4-amino-5-halogen-pyridazon-6-ones - Google Patents

Description

The present invention provides a process for the preparation of the known herbicidally active 1-phenyl-4-amino-5-halopyridaz-6-ones of the general formula I

where

X represents a halogen atom.

It is known that substituted pyridazones are used extensively as herbicidally active agents (see DE patent 1 105 832). It is further known that sugar beet has a specific resistance to these compounds. Therefore, these compounds are primarily used for the selective control of weeds in beet cultures (Chemical Rumors 19, p. 403 (1965)).

To prepare the compounds of formula I, arylhydrazines are generally condensed with 2,3-dihalo-3-formylacrylic acid (halo-muconic acid) and the dihalopyridazone derivative obtained is amidated.

In processes known from the literature, arylhydrazine as a starting material is generally prepared in advance (Org. Synth. Coll. Vol. I, p. 432/1932 / j), however, processes are also known in which dichloropyridazone is obtained in acid solution without intermediate isolation of arylhydrazine. (HU patent 164133).

The required 2,3-dihalo-3-formylacrylic acid is obtained according to known methods, for example from butyne-1,4-diol or by oxidative halogenation of furan derivatives (Annalen der Chemie, Suppl. 3, p. 279 (1964/65); Am. Chem. Journ. 19, 641 [1897]; FR patent 1443 740).

Dihalopyridazone is produced by ring closure of arylhydrazines (GB patent 881616, DE patent 1086 239), and it is not absolutely necessary to isolate the arylhydrazine.

Dihalopyridazones can also be prepared by the best literature procedures in yields of up to 70-75% only. They have a very toxic effect on the skin and have other effects harmful to human health.

The amidation of the dihalopyridazones produced by the described process is generally carried out in the melt (FR patent 1461373, Czechoslovak patent 120 858), but they are known in 192948

197248 and processes in which it is amidated in a solvent such as ethylene glycol. However, due to the difficulty in recovering the solvent and the formation of a considerable number of different isomers, this process is not preferred.

DE 1105 232 describes pressure amidation with ammonium hydroxide, but this process is not suitable for industrial scale practice due to the difficulties with the device. According to HU patent 164 133, dlhylogenpyridazones are amidated in solution in acid amides, for example in formamide.

A common disadvantage of all known methods is that in industrial practice, the harmful dihalopyridazones must be isolated, causing considerable work and health problems, since these compounds cause blistering on the skin, further causing swelling, exema and often causing allergy to each other.

The present invention provides a novel process for the preparation of 1-phenyl-4-amino-5-halopyridaz-6-ones. In the process according to the invention, the production of the substituted hydrazone and ring closure is carried out so that the reaction mixture formed. it is immediately suitable for subsequent amidation, i.e. the dihalopyridazone formed is not isolated.

A novel process according to the invention for the preparation of 1-phenyl-4-amino-5-halopyridaz-6-ones of the general formula I

where

X is a halogen atom, characterized in that the hydrazine derivative of the formula II i

CsH 5 -NH ₂ -NH ₂ (II) is reacted with a mineral acid in a mixture of apolar solvent and water to form salts which are reacted with a 2,3-dihalo-3-formylacrylic acid of general formula at 40-90 ° C III

COH

OF

X-C

Zl ·. 'y-c'

C — OH ·: 11 ’

O (III) where

X is as defined above, and Y is also a halogen atom, and the dihalopyridazone of formula IV formed

where

X and Y are as defined above,

is amidated without intermediate isolation with ammonia gas at a temperature in the range of 120 to 140 ° C.

Preferred solvents are those which form azeotropically boiling mixtures, for example toluene or xylene, with water.

The water resulting from the reaction of the compound of formula II with the compound of formula III by the process of the present invention can be removed advantageously from the reaction mixture in the form of an azeotropic mixture with toluene, and the distilled toluene is continuously replenished. .

For amidacl, additives which favorably influence this reaction, such as, for example, formamide and urea, may optionally be added.

The technical progress achieved by the process according to the invention over the prior art represented by the Austrian patent 321 926 is that in the process disclosed therein the highly toxic dihalopyridazines of the general formula IV, causing eczema, allergies and other dangerous skin diseases, are isolated. By specific measures of the process according to the invention, the isolation of these intermediates can be avoided so that the operator does not come into contact with them.

A further advantage of the process of the invention over the prior art is that it can be carried out in a single, easy-to-implement step with very good yields (83 percent in Example 2). Also, the reaction time is shorter and the product is obtained in a purity of 98 to 99%.

In summary, the most important advantages of the method according to the invention over the prior art are:

difficult to handle and harmful dihalopyridazones do not need to be isolated; the yields obtained by the process according to the invention are very good; almost no additional investment in equipment is needed;

197248 the degree of purity of the products obtained is higher than can be achieved by known methods. The compounds produced by the process of the invention have a purity in the range of 98 to 99%.

The process according to the invention is illustrated by the following examples.

Example 1.

A 2 L ball was charged with 600 g of toluene, 185 ml of water and 103.25 g of 36% hydrochloric acid. With vigorous stirring, 108.16 g (1 mol) of phenylhydrazine is added such that the temperature does not exceed 40 ° C. Then, 169 g (1 mol) of 2,3-dichloro-3-formylacrylic acid was added to the acidic reaction mixture, and the resulting mixture was stirred at 60 ° C for 1 hour, then at 90 ° C for 2 hours. The azeotropic mixture of toluene and water is then distilled off, whereby the distilled toluene is continuously replaced and the amount of distilled water is measured.

After distilling off the calculated amount of water, the mixture was freed from the solvent. 162.5 g of formamide, 26.0 g of urea and 40 g of xylene are added at a temperature between 110 and 120 ° C, after which the mixture is heated to 130 ° C and ammonia is introduced. Care should be taken that only small bubbles emerge at the end of the gas outlet pipe. The end of the amidation is determined by thin layer chromatography. When the reaction is complete, the mixture is cooled to 90 ° C, 900 g of water are added and the mixture is stirred at 85-90 ° C for 2 hours. After cooling the mixture to 15-20 ° C, the mixture is filtered and the product is washed with water and methanol and dried. There was thus obtained 1-phenyl-4-amino-5-chloro-pyridaz-6-one (175.3 g), m.p. 198 DEG-201 DEG. The yield, based on 2,3-dichloro-3-formylacrylic acid, was 79.1%.

Purity:

up to 99% (according to elemental analysis, CI)

98% (according to UV spectrum).

Example 2

A 250-liter Lampart autoclave was charged with 121 kg of toluene, 37.5 kg of water and 20.65 kg of 36% hydrochloric acid. While stirring, 21.60 kg (200 moles) of phenylhydrazine and 33.8 kg (200 moles) of 2,3-dichloro-3-formylacrylic acid are added, the temperature inside the autoclave not to exceed 40 ° C.

The reaction mixture was stirred at 60 ° C for 1 hour, then at 90 ° C for 2 hours, at which time an azeotropic mixture of toluene and water was distilled off at atmospheric pressure. The distilled toluene is continuously replaced. After distilling off the calculated amount of water, toluene is removed from the reaction mixture. Then 32.5 kg of formamide, 5.2 kg of urea and 7.76 kg of xylene are added at 110 to 120 ° C and the reaction mixture is heated to 130 ° C. Ammonia is then introduced, taking care that only a minimum amount of ammonia escapes from the mixture. The duration of the amidation is 3 to 5 hours, approximately 6 to 7 kg of ammonia being consumed. The end of the reaction was determined by thin layer chromatography. After completion of the reaction, the reaction mixture was cooled to 90 ° C and 180 kg of water were added. The mixture is then heated with stirring at 85-90 ° C for 2 hours, cooled to 15-20 ° C, the precipitated product is collected by centrifugation, washed with methanol and water and dried. 36.79 kg (83% of theory) of 1-phenyl-4-amino-5-chloro-pyridaz-6-one of melting point 196 DEG-202 DEG C. are obtained.

Purity:

98.5% (by elemental analysis, Cl) 98.2% (by UV spectrum) Example 3

A 2 liter spherical flask was charged with 600 g of toluene, 185 g and 103.25 g of 36% hydrochloric acid. While stirring and cooling, 108.15 g (1 mol) of phenylhydrazine is added dropwise such that the temperature does not exceed 40 ° C. Then, 213 g (1 mol) of 2-bromo-3-chloro-3-formyl acrylic acid was added to the acidic reaction mixture, and the mixture was stirred at 50 ° C for 1 hour, then at 90 ° C for 3 hours. The azeotropic mixture of toluene and water is distilled off.

The distilled toluene is continuously replaced, and the amount of distilled water is measured. After the calculated amount of water has been distilled off, toluene is removed from the reaction mixture, to which 400 g of xylene are added at 105 to 110 ° C. After the mixture has been heated to 130 ° C, ammonia is introduced and only a small amount of gas can escape from the reaction mixture. The end of the reaction was determined by thin layer chromatography. The reaction mixture was cooled to 90 ° C, 900 grams of water was added and stirred for 2 hours. The precipitated product is filtered off at a temperature between 15 DEG and 20 DEG C., washed with methanol and water and then dried. 1-Phenyl-4-amino-5-bromo-pyridaz-6-one is obtained with a purity of 99%. The melting point of the compound obtained is 216 ° C.

197248

Claims (3)

SUBJECT A process for the preparation of 1-phenyl-4-amino-5-halo-pyridaz-6-ones of the general formula I wherein X represents a chromium or bromine atom, from hydrazine derivatives and dihaloformyl acrylic acids, characterized in that the hydrazine derivative of the formula II C6H5-NH-NH2 (II), reacted in a mixture of a non-polar solvent and water with a mineral acid to form a salt which is reacted with a 2,3-dihalogen-3-formylacrylic acid of general formula at 40-90 ° C of formula III COH / X — c II Y-C \ C — OH O (III), I will invent where X is as defined above and Y is a halogen atom, and the resulting dihalopyridazone of formula IV wherein X and Y are as defined above, without isolating the amidated with ammonia gas at a temperature ranging from 120 to 140 C ^e 2. Process according to claim 1, characterized in that the solvent used is a solvent which forms an azeotropically boiling mixture with water, preferably toluene or xylene. 3. The process according to claim 1, wherein the reaction of the compound of formula III with the compound of formula II is carried out in toluene, the resulting water being removed as an azeotropic mixture with toluene and the distilled toluene being continuously charged. severografla, n. p. zívod 7, Most