DE2033895A1 - Process for the production of substituted pyndazones - Google Patents

Description

^ νΤ ^ ΛΤ " ¹ ' ⁸ ? Case 63O-63Q7 Dr. V. Schmied-Kowarzik ~ - -"

Dr. P. WeinhoU, Dr. D. Güdel jifrankfurj / ML, Gr. Eschenheimer S »r. 39

SANDOZ A. Cr.

Basel, Switzerland Process for the preparation of substituted pyridazones

The present invention relates to a new method for the preparation of substituted 5-chloropyridazones of Formula I.

? ^P 3

/ ^R l - ¹

ι Cl

wherein R is hydrogen or a lower alkyl group and Rp represent a lower alkyl group.

To establish the connections one uses multi-stage, relatively complex process. For example,> -trifluoromethylaniline of formula II

CF ₃

-NH ₂

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by diazotization into the corresponding diazonium cation of the formula III

in

transferred that with tin or tin compounds to 3-trifluoromethyl-phenylhydrazine of the formula IV

is reduced. The substituted phenylhydrazine IV is then mixed with mucochloric acid VI in alcohol or in mineral acid implemented, and then by treatment with glacial acetic acid and / or acetic anhydride, the compound V, 1- (3-trifluoromethylphenyl) »4j, 5-dichloro-pyridazon- (6) obtain,

which can be obtained by reaction with a multiple excess of an AmIn of the formula VII

VII

in which R 1 and R _{2 have} the meanings given above, can be converted into the compound of the formula I.

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The present application describes a process starting from 3-trifluoromethylaniline II using of water as a solvent in the various sub-steps makes the isolation of intermediate products unnecessary, apart from the fact that the individual steps omitted, the use of cheaper reagents and much smaller excesses of reagents is made possible. ·

According to the process according to the invention, the compounds of the formula I are prepared by aminolysis of 1- (3-trifluoromethylphenyl) -4,5-dichloro-pyridazon- (6) [V] with an amine of the formula VII, in which R _{1 is} hydrogen or is a lower alkyl group and R "is a lower alkyl group, in water as the solvent, the ratio being about 2.5 to 4 moles of amine of the formula VII per mole of the pyridazone derivative V.

As solvent additives to the aqueous phase, benzene, xylene, hexane, heptane or halogenated hydrocarbons, such as chloroform or chlorobenzene, preferably toluene, use. The reaction can take place at temperatures between approx. 65 and 95 °, but advantageously at the reflux temperature of the solvent system during 1 up to 10 hours. The isolation of the * Product happens according to the usual methods.

The 1- (3-Ti ^t ifluoromethylphenyl) -4,5-dichloropyridazon- (6) [V] can be obtained from 3-trifluoromethylhydrazine (IV) by condensation with mucochloric acid [VI] in an inert solvent, such as, for example, Benzene, toluene, xylene, hexane, heptane or halogenated hydrocarbons such as chloroform or chlorobenzene

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zol. The preferred solvent is toluene. The reaction is carried out at temperatures between about 40 and 135 °, advantageously at the reflux temperature of the solvent carried out within 1 to 4 hours. The reaction product V can, if necessary, after isolate traditional methods.

Since this process for the preparation of the compound V compared to the known process, the two reaction stages need, represents a decisive improvement,

"this means a further advantage of the invention Procedure.

The compound IV is obtained according to the invention by reducing the diazonium ion III with sulfite anions in aqueous solution, such as are present when using an alkali metal sulfite of the sodium or potassium sulfite type or when using sulfur dioxide. The reactants are allowed in a range of -5 ° to about 110 ⁰ C interact. The reaction takes place under acidic conditions, preferably at a pH of 3 and below. Two-stage temperature control is also preferred because of the higher yield. The first contact of the reactants takes place at a temperature of -5 ° to 10 °. After this first contact phase, the course of the reaction can be accelerated by heating for 3 to 6 hours to approximately 60 to 110 °; The boiling point of the reaction mixture is advantageous here. If necessary, the reaction product IV can be isolated in a customary manner.

The diazonium cation III is obtained by diazotization of 3-trifluoromethylaniline II with an alkali nitrite, such as

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ORIGINAL BATHROOM

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e.g. sodium or potassium nitrite in aqueous solution in Presence of a strong mineral acid, e.g. a hydrohalic acid such as hydrobromic acid, sulfuric acid, Phosphoric acid and the like, preferably with hydrochloric acid. The diazotization can take place in the course of about 1/2 to 2 1/2 Hours at temperatures of approx. -10 ° to 15 ° will.

The compounds of the formulas II and VI are described and can be prepared by known methods.

The peculiarity of the method according to the invention lies in that in the preparation of the compound I the intermediates of the formulas III, IV and V without isolation can be used directly for the next step can. In addition, the present proceedings in It differs from the known modes of presentation to very pure compounds of the formula I, and to that extent to higher ones Exploit.

The compounds of formula I can be used as selective herbicides, for example in cotton.

The following examples serve to illustrate the preparation of the compounds according to the invention, they are intended however, do not limit the invention in any way. The temperatures are given in degrees Celsius.

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Example 1; Preparation of 1- (3-trifluoromethylphenyl) - ² lN, N-diraethylamino-5-chloropyridazone- (6)

| 96.6 g of 3-trifluoromethylaniline were added to 300 g of ice and 180 ml of concentrated hydrochloric acid over the course of 20 minutes, the temperature being kept between 0 and 10 °. The resulting reaction mixture is cooled to 0 ° and a solution of 43.5. & Sodium nitrite in 420 ml water is added dropwise over 20 minutes while maintaining the temperature at O °. The resulting clear solution of the 3-fluoromethyl-diazonium salt is stirred for 15 minutes at 0 °, and after the addition of 15 g of urea for a further 30 minutes at 0 °. The diazonium solution produced in this way quickly, within 10 minutes, becomes a solution of 227 g of sodium sulfite in 1000 ml

^ Given water at 0-5 °. One makes sure that the The temperature remains below 7 °, and a light orange, almost clear solution is obtained. The solution is under vigorous Stirring held at 5 - 10 ° for another 30 minutes, and then the temperature is then increased to 60 ° for a further 60 minutes. 195 ml of conc. Hydrochloric acid to the hot solution, and the resulting reaction solution is kept at 60-70 ° for 30 minutes, then under reflux for 3 hours heated, then cooled to 20 ° and left to stand overnight. Then 300 ml of 50 # strength sodium hydroxide solution are added added, the temperature being kept below 50 °.

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The deposited oil is extracted with 700 ml of toluene and then twice with 150 ml of toluene each time. The combined toluene extracts are washed with 150 ml of saturated sodium chloride solution. The toluene solution, which contains the> -trifluoromethylphenylhydrazine, is transferred to a reaction vessel, and 98 g of mucochloric acid are added to this. The reaction mixture is refluxed for 2 hours. The solvent, which contains 1- (3-fluoromethylphenyl) -4,5-dlchloropyridazon-6, is drawn off until about 100 ml of toluene are still present in the reaction vessel. Add 700 ml of water to this; the resulting suspension is cooled to 70 to 30 °. Then 200 ml of a 40% solution of dimethylamine in water are added, and the resulting mixture is heated to 80-85 ° for 2-3 hours. The remaining toluene is evaporated, the reaction mixture is cooled to 20 ° and the precipitate which has separated out is washed 3 times with 500 ml of water. This gives 182 g of 1- (3-trifluoromethylphenyl): - ¹ IN, M-dimethylamino - ^ - chlorpyridazone- (6) with a melting point of 130-149 ⁰ (yield based on 3-trifluoromethylaniline: 95%). "

A part by weight of the crude product is used for pure preparation suspended in 2 parts by weight of ether and stirred for 15 minutes at 20 °. Then it is filtered off and washed twice with 1/2 part by weight of ether. After drying, the product melts at 148-151 °.

Example 2:

The example describes a variant of the reduction.

The diazonium salt solution prepared according to Example 1, first section is added dropwise within 30 minutes

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to a saturated solution of sulfur dioxide (500 g) in 3 liters of water at 0-10 °, while sulfur dioxide gas is simultaneously blown through the solution. The passage of sulfur dioxide through the solution is continued for 5 minutes beyond the dropwise addition of the diazonium solution, then the reaction mixture is allowed to stand overnight at room temperature. Then you give 15Ο ml of conc. Hydrochloric acid to the reaction mixture and the solution is refluxed for 2 hours while nitrogen is bubbled through. After cooling to 20 °, 700 ml of toluene are added. To this mixture is added dropwise with stirring, a 300 ml of 50 $ aqueous sodium hydroxide solution, the temperature being kept below 3O ^0th The water phase is then separated from the toluene phase, and the water phase is washed twice with 150 ml of toluene each time. The combined toluene phase is washed with 150 ml of a saturated sodium chloride solution. It contains the resulting 3-trifluoromethylphenylhydrazine. You can then continue working according to Example 1.

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Claims (2)

Patent claims: 1. A process for the preparation of compounds of the formula I. wherein R- is hydrogen or a lower alkyl group and Rp represent a lower alkyl group, thereby characterized that 3 ~ trifluoromethylanlline in aqueous Solution is reacted with nitrite ions in the presence of a strong mineral acid, the reaction solution is reduced in water under acidic conditions and then with mucochloric acid in a solvent which is inert under the reaction conditions and finally with an amine of the formula VII HNR R ₂ . VII wherein R _{1 is} hydrogen or a lower alkyl group and Rp is a lower alkyl group, is reacted. 2. The method according to claim 1, characterized in that das3 is used as an inert solvent under the reaction conditions, toluene. j5. Method according to claim 1, characterized in that because the mineral acid used is hydrochloric acid. 0098 83/22 79