RU2707043C1 - Method of producing imazamox herbicide - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to production of pesticides, in particular to the technology of producing an impervious imazamox herbicide, having a chemical structure (±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-(methoxymethyl)-3-pyridinecarboxylic acid. Method of producing (±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-(methoxymethyl)-3-pyridinecarboxylic acid (imazamox) includes synthesis of imazamox salt from 5-methoxymethyl-2,3-pyridine dicarboxylic acid dimethyl ester and (±)-2-amino-2,3-dimethylbutyramide in the presence of sodium or potassium tert-butoxide in toluene or xylene while heating, dissolution of the obtained salt in water and separation of toluene or xylene, subsequent conversion of the obtained imazamox salt to the end product under action of hydrochloric or sulfuric acid and extraction of the end product. Moisture is previously removed from solution of 5-methoxymethyl-2,3-pyridine dicarboxylic acid dimethyl ether and (±)-2-amino-2,3-dimethylbutyramide in toluene or xylene by azeotropic distillation, and the process of producing the imazamox salt is carried out in an atmosphere of an inert gas. Obtained solution of imazamox salt is purified at stirring with 6–12 wt% of activated carbon in terms of initial dimethyl ester of 5-methoxymethyl-2,3-pyridine dicarboxylic acid for 1–2 hours and spent activated carbon is filtered. Obtained imazamox salt solution is acidified to acidic pH values, the precipitated residue of the end product is separated by filtration, washing with water and drying.

EFFECT: disclosed method of producing (±)-2-[4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl]-5-(methoxymethyl)-3-pyridinecarboxylic acid (imazamox) provides simplified process of imazamox production, which is expressed in the fact that the use of an anhydrous solvent is excluded, the extraction stages are excluded with high-corrosion solvents, the organic extract is dried and purified, the organochloride compounds evaporated, and the end product yield is equal to 83,6 %.

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Description

The invention relates to the field of production of pesticides. More specifically, the invention relates to a technology for the production of a post-emergence imazamox herbicide having the chemical structure of (±) -2- [4,5-dihydro-4-methyl-4- (1-methylethyl) -5-oxo-1H-imidazole-2- yl] -5- (methoxymethyl) -3-pyridinecarboxylic acid (I). His registration number is in the CAS Chemical Abstracts Service Registry of Chemical Abstracts Service [114311-32-9]. Hereinafter referred to as "imazamox."

As a result of a patent search, the following patents were selected.

In international applications WO No.2010055042 and WO No.2010066669 a method for producing (±) -2- [4,5-dihydro-4-methyl-4- (1-methylethyl) -5-oxo-1H-imidazol-2-yl] is disclosed -5- (methoxymethyl) -3-pyridinecarboxylic acid from 5-methoxymethyl-2,3-pyridinedicarboxylic acid. The multistage process involves the preparation of 5-methoxymethyl-2,3-pyridinedicarboxylic anhydride from 5-methoxymethyl-2,3-pyridinedicarboxylic acid by its reaction with acetic anhydride, acylation of the obtained 5-methoxymethyl-2,3-pyridinedicarboxylic anhydride with 2-amino 2,3-dimethylbutyronitrile, hydrolysis of the obtained 2 - [[(1-cyano-1,2-dimethylpropyl) amino] carbonyl] -5- (methoxymethyl) pyridine-3-carboxylic acid under acidic conditions, intramolecular cyclization of the obtained 2- [ [[1- (aminocarbonyl) -1,2-dimethylpropyl] amino] carbonyl] -5- (methoxymethyl) -p iridine-3-carboxylic acid under alkaline conditions and the isolation of imazamox from the resulting salt under acidic conditions. The disadvantage of the described method is the high stages, a large number of technological operations, the need to use controlled acetic anhydride (Decree of the Government of the Russian Federation of June 30, 1998 No. 681 “On approval of the list of narcotic drugs, psychotropic substances and their precursors to be controlled in the Russian Federation”) and the complexity of technological implementation.

A known method of obtaining an optically active form of imazamox. US Pat. No. 5,973,154 provides an example of the preparation of 2 - [(4R) -4,5-dihydro-4-methyl-4- (1-methylethyl) -5-oxo-1H-imidazol-2-yl] -5- (methoxymethyl ) -3-pyridinecarboxylic acid CAS [221298-64-2]. It consists in the interaction of 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ester with (R) -2-amino-2,3-dimethylbutyramide in anhydrous toluene in the presence of potassium tert-butylate and subsequent decomposition of the resulting potassium salt of (R) -imazamox concentrated hydrochloric acid. Isolation of the target product is carried out by extracting the mass after acidification with methylene chloride, drying the extract over magnesium sulfate, purifying the extract using silica, filtering and removing the solvent under reduced pressure. The main disadvantages of the described method are the use of anhydrous solvents in the synthesis of imazamox salt and the technological difficulty of isolating the target product with a large number of technological operations. The product precipitated after acidification is extracted exclusively with methylene chloride. The use of this low-boiling (T _boil = 40 ° C) flammable (T _boil = -14 ° C) organic solvent leads to large losses during its distillation and regeneration. It is also known that this solvent is highly corrosive, which imposes increased requirements on equipment materials. The yield of imazamox is 73.5%, which is close to moderate.

The objective of the proposed technical solution is to improve technical and economic indicators and simplify the process of obtaining imazamox (I).

The technical result is the simplification of the technological process for the production of imazamox, which is expressed in the fact that the use of anhydrous solvents is excluded, the stages of extraction with methylene chloride, drying and purification of the organic extract, and evaporation of methylene chloride are excluded. As a result, the yield of the target product is increased to 83.6%.

The technical result is achieved by using the method of producing (±) -2- [4,5-dihydro-4-methyl-4- (1-methylethyl) -5-oxo-1H-imidazol-2-yl] -5- (methoxymethyl) -3-pyridinecarboxylic acid (imazamox) (I), including the synthesis of the imazamox (IV) salt from 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ether (II) and (±) -2-amino-2,3-dimethylbutyramide ( III) in the presence of sodium or potassium tert-butylate in toluene or xylene when heated, dissolving the obtained salt in water and separating the toluene or xylene, then converting the obtained imazamox salt to the target product under the action of hydrochloric or sulfuric acid and isolation of the desired product. The moisture is preliminarily removed from a solution of 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ether and (±) -2-amino-2,3-dimethylbutyramide in toluene or xylene by azeotropic distillation, the imazamox salt is prepared in an inert gas atmosphere, and the resulting solution imazamox salts are purified with stirring from 6-12 mass. % activated carbon (based on the starting 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ether) for 1-2 hours, the spent activated carbon is filtered off, the resulting imazamox salt solution is acidified to pH values, the precipitated precipitate of the target product is isolated by filtration, washing with water and drying.

M = Na, K; solvent = toluene, xylene; H ⁺ = HCl, H ₂ SO ₄ .

The invention is illustrated by the following examples.

Example 1 (comparative prototype).

A mixture of 21.54 g (0.09 mol) of 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ester II and 12.09 g (0.0993 mol) of (±) -2-amino-2,3-dimethylbutyramide III in anhydrous toluene stirred at room temperature for 15 minutes, added 9.12 g (0.095 mol) of sodium tert-butylate, kept under stirring for 5 minutes and added another 9.12 g (0.095 mol) of sodium tert-butylate. The reaction mass is heated with stirring until the compound II is fully activated (TLC control). At the end of the reaction, the reaction mass is cooled to room temperature and water is added with stirring to dissolve the imazamox sodium salt. It is stirred until the solid phase is completely dissolved in water, stirring is stopped and the resulting two-phase system is allowed to separate. The aqueous phase, which is a solution of the imazamox sodium salt, is separated, concentrated sulfuric acid is added to it with a stirring to pH ~ 3 and extracted twice with methylene chloride. The extracts are combined, the combined extract is dried over magnesium sulfate, silicon dioxide is added to it, stirred and filtered. The filtrate was evaporated to dryness under reduced pressure. 19.8 g of imazamox powder are obtained. Yield 72.1%.

Example 2 (the inventive method).

450 g (1.88 mol) of 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ester II, toluene are charged into an imazamox salt synthesis reactor, and 252.3 g (1.94 mol) of 2-amino-2 are added with stirring. 3-dimethylbutyramide III. To remove moisture from the resulting solution introduced with the feed and solvent, the reactor is vacuumized, heated and the moisture is distilled off in an azeotropic mixture with the solvent. After this, the evacuation is stopped and nitrogen is fed into the reactor. To a solution of room temperature, 191.4 g (1.99 mol) of sodium tert-butylate are added with stirring, kept under stirring for 5 minutes and another 191.4 g (1.99 mol) of sodium tert-butylate are added. The reaction mass is heated with stirring with a continuous supply of nitrogen until the compound II is fully activated (TLC control). At the end of the reaction, the contents of the synthesis reactor are pumped to the isolation reactor, cooled to room temperature and water is added with stirring to dissolve the imazamox sodium salt. Stir until the solid phase is completely dissolved in water, stirring is stopped and the resulting two-phase system is allowed to separate. An aqueous phase of imazamox sodium is separated into a purification reactor. 6-12 masses are added to the alkaline aqueous phase in the purification reactor. % activated carbon (calculated as compound II), stirred for 1-2 hours and filtered from the spent carbon into the acidification reactor. Concentrated sulfuric acid is added to a purified solution of imazamox sodium salt in an acidification reactor with stirring to a pH of ~ 3. The resulting suspension is filtered, the filter cake is washed three times with water and dried in air. 480.2 g of imazamox powder are obtained. Yield 83.6%.

Example 3

The method of obtaining imazamox was carried out analogously to example 2. The difference was in the use of potassium tert-butylate as a base and xylene as a solvent. 460.1 g of imazamox powder are obtained with a yield of 80.1%.

As a result of using the proposed method, the technological process as a whole is greatly simplified. The number of technological operations is reduced, the complicated stage of solvent distillation to a dry residue is eliminated. The use of an anhydrous solvent for the synthesis of the imazamox salt is excluded; the use of a boiling highly flammable organic solvent (methylene chloride) is excluded. Process indicators are improving. The yield of the target product of imazamox increases by 11.5% and amounts to 83.6%. The solvent can be regenerated with a return to the process up to 85% of the amount used.

Claims (1)

The method of obtaining (±) -2- [4,5-dihydro-4-methyl-4- (1-methylethyl) -5-oxo-1H-imidazol-2-yl] -5- (methoxymethyl) -3-pyridinecarboxylic acid (imazamox), including the synthesis of an imazamox salt from 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ether and (±) -2-amino-2,3-dimethylbutyramide in the presence of sodium or potassium tert-butylate in toluene or xylene with heating, dissolving the obtained salt in water and separating toluene or xylene, then converting the obtained imazamox salt to the target product under the action of hydrochloric or sulfuric acid and isolating the target product, characterized in that the moisture is preliminarily removed from a solution of 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ether and (±) -2-amino-2,3-dimethylbutyramide in toluene or xylene by azeotropic distillation, the imazamox salt is prepared in an inert gas atmosphere, the resulting imazamox salt solution is purified with stirring with 6-12 wt.% activated carbon based on the starting 5-methoxymethyl-2,3-pyridinedicarboxylic acid dimethyl ether for 1-2 hours, the spent activated carbon is filtered off, the resulting salts of imazamox solution was acidified to acid pH values, the desired product precipitated is isolated by filtration the precipitate washing with water and drying.