DE1099544B - Process for the preparation of new pyridazine derivatives - Google Patents

Description

GERMAN

The present invention relates to a process for the preparation of new pyridazine derivatives the general formula

R,

X-CH-COOR ₁

, N

(D

wherein X is an oxygen or sulfur atom, R ₁ and R _{2 are} a hydrogen atom or a lower alkyl radical and Y is the radical

-X-CH-COOR ₁

Method of manufacture
of new pyridazine derivatives

Applicant:

Lentia
Company with limited liability

Buying and selling,
Munich, Mittererstr, 3

Claimed priority:
Austria from October 10, 19S8

Dr. Lothar Holzer, Munich,

and Dr. Rupert Schönbeck, Leonding (Austria),

have been named as inventors

or a halogen atom.

It has been found that the pyridazine derivatives of the formula I are hormone-acting, selective herbicides, which do not attack monocot plants and are therefore used to control weeds in cereals and grass are suitable. It is particularly noteworthy that these compounds are in their selectivity properties differ significantly from the halogenated phenoxyacetic acids previously used for this purpose and of these substances also such weed species as Lapsana communis and Galium aparine, are attacked, which are resistant to 2,4-dichlorophenoxyacetic acid, while on the other hand again some Weeds that are sensitive to 2,4-dichlorophenoxyacetic acid, such as Erodium cicutarium Treatment with the new pyridazine derivatives are hardly damaged.

It is true that the German Auslegeschrift 1 035 398 means for influencing plant growth became known, which among other things also substituted pyridazines, such as 3,6-dichloropyridazine, 3,4,6-Trich] orpyridazine, 3-chloro-6-methoxypyridazine and 3,6-dimethoxypyridazine as an active ingredient may contain. However, these pyridazine derivatives are not selectively effective hormonal ones Herbicide, but, as has been shown in experiments, in the case of 3,4,6-trichloropyridazine by one Corrosive total herbicide, while 3,6-dichloropyridazine, S-chloro ^ o-methoxypyridazine and 3,6-dimethoxypyridazine are not herbicidally effective at all. In addition, these new connections also show pharmacologically interesting properties.

The new compounds are prepared by reacting halopyridazine derivatives of the general type formula

Shark

Hal

with α-substituted carboxylic acids or their derivatives of the general formula

R ₂
MeX-CH-COOR ₃

(HD

in which R _{3 is} a hydrogen atom, an alkali metal ion, the equivalent of an alkaline earth metal ion or a lower alkyl radical, Me is an alkali metal ion or the equivalent

109 510/427

an alkaline earth metal ion and _: R ₂ and X are as defined above, in a molar ratio of 1: 1 or 1: 2 in the presence of a polar solvent, 1 or 2 equivalents of metal halide being split off.

In the pyridazines produced in this reaction Derivatives can then convert any ester groups that may be present into the free ones by saponification Carboxylic acid groups are converted.

The inventive implementation of the halopyridazines with the α-substituted carboxylic acids or their derivatives in the presence of a polar solvent, such as water, methanol or ethanol, and made at a slightly elevated temperature. It does not matter whether the O- or S-alkali metal compounds of the α-substituted carboxylic acids are used or their derivatives are used as such or whether they are from the free oxy or mercapto acids or from their derivatives and the corresponding amount of alkali are generated in situ during the reaction.

With the method according to the invention it is possible, for example, to use both a " also to bring both halogen atoms to react with the α-substituted carboxylic acid derivative. Whether the mono or disubstitution product arises, is mainly due to the choice of the molar ratio of the starting materials influenced. A major advantage of the process according to the invention is that it enables derivatives of mono- or dioxy or mono- or dimercaptopyridazines can be prepared without being used for Production of the free oxy or mercaptopyridazines must be assumed because of the in this Body class occurring keto-enol tautomerism is uncomfortable are to be handled. In addition, this process gives the pyridazine derivatives of the formula I in excellent yield, mostly in excess of 90%, and excellent purity.

The parts given in the following examples are parts by weight:

example 1

40

50 parts of 70% glycolic acid solution are placed in a stirred flask neutralized with 25 parts of calcined soda; then 10 parts of caustic soda are dissolved in 20 parts Water, added. 37 parts of 3,6-dichloropyridazine are added to this mixture at 60.degree. C. and the reaction mixture is stirred at 60.degree. C. for 2 hours. For work-up 150 parts of water are added and the amount of unreacted dichloropyridazine (12.8 parts) is filtered off. The mother liquor is then acidified with sulfuric acid. 28 parts of (3-chloropyridazine-6-oxy) acetic acid are obtained from the decomposition point 142 to 145 ° C. Equivalent weight: 188.5, yield: 91% based on converted dichloropyridazine.

55

Example 2

2.3 parts of sodium are dissolved in 40 parts of absolute ethanol and 12.2 parts of ethyl thioglycolate in a stirred flask added in 40 parts of absolute alcohol, whereupon the mixture is boiled for 5 minutes. Then 14.9 parts of 3,6-dichloropyridazine in 40 parts of absolute ethanol are added and the reaction mixture Boiled for 2 hours on the reflux condenser. For work-up, the sodium chloride formed (5.9 parts) suctioned off, the filtrate evaporated in vacuo and the oily residue with 100 parts of 10% sodium hydroxide solution saponified by boiling for an hour. Then will acidified with hydrochloric acid and the product crystallized in the refrigerator. 19.2 parts are obtained (S-Chlorpyridazine-ö-mercapto) -acetic acid from the point of decomposition 136 ° C and equivalent weight 204.5, that is 94% of theory.

Example 3

In a stirred flask, 18.4 parts of sodium are dissolved in 320 parts of absolute ethanol, 100 parts of thioglycolic acid ethyl ester and then a solution of 60 parts of 3,6-dichloropyridazine in 160 parts of absolute Ethanol was added and the reaction mixture was boiled for 2 hours on a reusable condenser. The separated table salt is filtered off with suction, the filtrate is evaporated and crystallized in the refrigerator.

After recrystallization from benzene, 123 parts of the diethyl ester of 3,6-bis (carboxymethyl-mercapto) -pyridazine are obtained obtained from a melting point of 52 to 53 ° C., that is 97% of theory.

31.6 parts of the diethyl ester of 3,6-bis- (carboxymethyl-mercapto) -pyridazms are refluxed with 150 parts of 10% sodium hydroxide solution for 30 minutes. The mixture is then cooled and adjusted with concentrated hydrochloric acid to a _pH value. 1 The 3,6-bis (carboxymethyl-mercapto) -pyridazine is brought to crystallization at 0 ° C. and deposited. 25.2 parts are obtained, that is 97% of theory. Decomposition point: 130 ° C, equivalent weight: 130.

Example 4

45 g of 73% strength lactic acid are mixed with a solution of 28 g of caustic soda in 63 ml of water and then 33.5 g of 3,6-dichloropyridazine are added to the mixture. This mixture is stirred intensively at 65 ° C. for 2 hours. The alkaline reaction solution thus obtained (3.5 g) by extraction with benzene from 3,6-dichloropyridazine and freed by further shaking at p _H 7 from 3-Chlorpyridazon-6, and then with concentrated hydrochloric acid to a _pH value of 1 acidified, whereby the d, la- (3-chloropyridazine-6-oxy) -propionic acid precipitates. By extracting the mother liquor with ethyl acetate, further proportions of (3-chloropyridazine-6-oxy) propionic acid can be obtained. A total of 26 g is obtained, that is 64% of theory. Melting point after recrystallization from water 165 ° C.

Claims (2)

Patent claims: 1. Process for the preparation of new pyridazine derivatives of the general formula X-CH-COOR ₁ N
.N wherein X is an oxygen or sulfur atom, R ₁ and R _{2 are} a hydrogen atom or a lower alkyl radical and Y is the remainder -X-CH-COOR ₁ I.
R ₂ or stands for a halogen atom, thereby marked draws that halopyridazine derivatives of the general formula (H) Shark with α-substituted carboxylic acids or their derivatives of the general formula R- 15th MeX-CH-COOR ₃ (III) in which R _{3 is} a hydrogen atom, an alkali metal ion, the equivalent of an alkaline earth metal ion or a lower alkyl radical, Me is an alkali metal ion or the equivalent of an alkaline earth metal ion and R ₂ and X are as defined above, in a molar ratio of 1: 1 or 1: 2 in the presence of a implemented polar solvent and then any ester groups present are converted into the free carboxylic acid groups by saponification. 2. The method according to claim 1, characterized in that the α-substituted carboxylic acid derivatives the formula R, MeX-CH-COOR, (III) from the free oxy or mercapto compounds of the formula R, HX-CH-COOR. (IV) and the corresponding amount of alkali being formed in situ during the reaction, the symbols X, R ₂ , R ₃ and Me being as defined in claim 1 in the above formulas (III) and (IV). Considered publications:
German Auslegeschrift No. 1 035 398;
Angew. Chemie, 1958, p. 8, section b. When the registration was announced, five pages of the investigation report were laid out. © 109510/427 2nd & 1st