SI8811792A8 - Process for preparation of anilinofumarate - Google Patents

Description

PROCEDURE FOR OBTAINING ANILINOFUMARATE

Technical field

The invention relates to the field of organic chemistry, and more closely to the field of processes for the preparation of fumarates as starting materials for the production of carbonic acids.

Technical problem

A technical problem to be solved by the present invention is how to provide a process for the direct production of anilino fumarates.

The state of the art

The herbicidal pyridine and quinolinimidazoline compounds obtained from the present compounds include 2- (4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl) quinoline-3-carboxylic acid, esters and their salts and are disclosed in the European Patent Application 0 041 621 (incorporated herein by reference). These herbicidal imidazolyl carboxylic acids can be prepared by the procedure described in Unated States Patent 4,518,780 (incorporated herein by reference), cyclization under basic conditions, of the corresponding substituted 2-carbamyl-quinoline-3-carboxylic acid, obtained by the reaction of an substituted anhydride-2-quinoline , 3-dicarboxylic acid and appropriately substituted aminocarboxamide or aminothiocarboxamide. Quinoline-2,3-dicarboxylic acid anhydrides are prepared from the diacid using a method well known in the art. However, the acids themselves are not readily available. A useful process for preparing quinoline-2,3-dicarboxylic acid and its esters by reacting the beta-anilino-alpha, beta-unsaturated ester with the ammonium salt (commonly referred to as Vilsmeier reagent) is affordable ^! i

in the same application filed. Beta-anilino-alpha, beta-unsaturated and esters are obtained by reacting suitably substituted aniline with beta-esters or dialkyl-acetylene dicarboxylates. This overall reaction for quinoline-2,3-dicarboxylate is illustrated in j ί

Schemes 1.

u kojoj R 'is CH or CC ^ ^ R and R is a C ^ -C ^ alkyl; or R'^'1 is CH ₃ or ^c -j ^"C 4 alkyl).

When R 'is CH _{3 the} diacid is obtained by comparative oxidation and hydrolysis of the product under water-base conditions in the presence of nickel-peroxy as described in United States Patent 4,449,409.

Unfortunately, the accessibility of ketoesters and diallulaethylene dicarboxylate

L · such as diethyloxalaoetate and diethylethylene-dicarboxylate is limited, thereby limiting the amounts of anilino-fumarate and quinoline-2,3-dicarboxylic acid, intermediates required for the preparation of the herbicidal 2- (4-isopropyl-4-methyl- 5-Oxo-2-imidazolin-2-yl) quinoline-3-carboxylic acid, esters and their salts.

- 3 Description of a solution to a technical problem

A process for the preparation of anilino fumarates of formula IV:

wherein R is (C 1 -C ₄ ) alkyl, is carried out by reacting a compound of formula I:

Cl - CH -CO_R I · ²

Cl - CH -CO ₂ R wherein R is as defined above with the mole equivalent of aniline in an inert organic solvent, such as a hydrocarbon, aromatic hydrocarbon, blocked aromatic hydrocarbon, aromatic hydrocarbon or mixtures thereof, said solvent being chlorinated aromatic hydrocarbon hydrocarbon or mixtures thereof, and two or more molar equivalents of aqueous base such as 15 to 50% by weight of sodium hydroxide, potassium hydroxide or mixtures thereof and in the presence of an intermediate phase catalyst such as quaternary ammonium salt consisting of such salts as N-butylammonium chloride, benzyltriethylammonium chloride or mixtures thereof at a temperature of from about 20 ° C to about 90 ° C for 1 to 24 hours.

The present invention relates to the following new process for the preparation of anilinofumarates. This process involves reacting dichlorosuccinate of formula I:

Cl - CH - CO RI ²

Cl - C £ - CO ₂ R wherein RC 1 -C 4 alkyl is with an aniline mole equivalent and a minimum of 2 mole equivalents (equivalent to or more than 2 mole equivalents) of an aqueous base in the presence of an intermediate phase catalyst in an organic solvent at a temperature of about 80 ° C to about 90 ° C for about 1 to 24 hours, and isolating the resulting anilinofumarate.

-4 The above reaction is graphically illustrated in Scheme II.

Scheme II

Suddenly, it has been found that aniline can react with dialkyldichlorosuccinates by the process of the present invention, yielding anilino fumarate directly. This process eliminates the process step required in recently discovered new syntheses of anilinofumarate by first reacting dialkildihlorsuccinate with the primary or secondary amine and then reacting the resulting product mixture with aniline.

The new process of the present invention thus provides a simple and direct process for the preparation of anilino fumarate. This process also reduces processing. flows and exposure to intermediate reactions and reagents. resulting in a process that is cleaner, safer, less costly and more efficient than those listed above.

In accordance with the process of the present invention. diethyldichlorosuccinate (0.01 mol) by stirring the mixture in the presence of 0.3 molar equivalent of aqueous sodium hydroxide (33% NaOH w / w) and a catalytic amount (5 mol%) of tetrabutylammonium chloride at 75 ° C-80 ° C for 2 hours and 30 minutes. The resulting anilinofumarate is easily isolated by the addition of water. by washing the organic layer, separating the organic phase and removing the solvent.

An aqueous base suitable for the preparation of anilino fumarate by the present invention includes sodium and calcium hydroxide. carbonate or bicarbonate at concentrations of 15% to 50% by weight, in quantities sufficient to provide 2 molar equivalents of base base. and hence the previously identified bases are conveniently used with 1-3 molar equivalents. Carbonates are used with about 1-3 molar equivalents and bicarbonates and hydroxides of salt They are used with approximately 2-3 molar equivalents.

Quaternary ammonium intermediate phase catalyst !. such as tetrabutylammonium chloride and benzoltriethyl ammonium chloride. in quantities as small as 0.05 molar equivalents. show comparative results for the process of the present invention. Other reagents capable of catalyzing biphasic reactions and exhibiting stability under the conditions of this reaction are equivalent to stable.

It has suddenly been found that using 1.1 to 3.0 molar equivalents of 15% to 50% aqueous sodium carbonate or potassium carbonate. suitable with the use of 2-10% mol., tricapryylmethylammonium chloride or tetrabutylammonium chloride results in unexpectedly high yields of anilinofumarate.

In general, organic solvents that have been used in the process of the present invention are inert to the reaction conditions and include such solvents as hydrocarbons. aromatic hydrocarbons and their chlorinated derivatives. with chlorinated aromatic hydrocarbons. such as chlorbenzene. and aromatic solvents, such as toluene. which are convenient.

The reaction of the invention is carried out at different speeds in the temperature range from about 20 ° C to 90 ° C. with a suitable range of 20 ° C to 85 ° C, most preferably 20-80 ° C.

The methods of the present invention are further exemplified by the following examples, which are illustrative in the following in limitation.

Example '1

Preparation dihlorsukcinata ^HC * i ° 2 ^C 2 ^H 5

HOCOjC.H.

EtOH Cl-Ol-COjCjHg

ClT-> | (cat) C1-CH-CO ₂ C ₂ H ₅

Chlorine gas is introduced by bubbling into an ethylenedichloride solution of 1maleate diet containing ethanol. (0.1 molar equivalent). After stirring the mixture at room temperature for 8 hours. it was covered with nitrogen gas for 5 minutes and the solvent was removed under reduced pressure to give dichlorosuccinate in 54% yield.

Example 2-14

Preparation of diethylanilinofumarate

C1-CH-CO ₂ C ₂ H ₅ ci-chh-co ₂ c ₂ h ₅

monochlorbenzone © Θ nc ₄ H _with Hcx

Aniline (0.53 g) <0.01 mol) was added to a stirred solution of diethyldichloroacetate; r t '

U (obtained as described in Example 1 above. From diethylimalear (0.01 mol) in monochlorobenzene). Aqueous sodium hydroxide (3.6 g, 33% w / w 0.03 mol) and tetrabutylammonium chloride (0.14 g 0.005 mol) were then added. at room temperature. The resulting mixture was stirred at 75 ° C to 80 ° C for 2 hours and 30 minutes. The mixture was then cooled to room temperature, and water (10 ml) was added to the stirred mixture. The aqueous layer was separated and the resulting organic solution analyzed for anilino fumarate by gas-liquid chromatography. Isolation of the product, by removing the solvent, yields 1.25 g of anilinofumarate.

Using a pre-treatment with different interfacial catalysts. aqueous bases of different concentrations and solvents. provide anilinofumarate as illustrated in Table II.

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Claims (2)

PATENT REQUEST r Ρ-1792/88 3o.4oo Div 1 522oP 1. A process for the preparation of anilino fumarates of formula IV: in which R (C 1 -C 6 alkyl) is a compound of formula I: by reacting Cl - CH - CO R and ² Cl - CH - CO R M In which R is previously defined, with the mole equivalent of aniline in an inert organic solvent, such as monochlorobenzyl or toluene, in the presence of two or more mole equivalents of an aqueous base, such as 15 to 5% by weight of sodium hydroxide, potassium hydroxide or mixtures thereof and in the presence of an intermediate phase catalyst such as a quaternary ammonium salt consisting of such salts as N-butylammonium chloride, benzyltriethylammonium chloride or mixtures thereof at a temperature of from about 2oC to about 9oC for 1 to 24 hours . 2. The process of claim 1, characterized by t and m e, being a base of 1.1 to 3, o molar equivalents of 15-5% by weight of sodium carbonate, potassium carbonate or a mixture thereof, and being a quaternary ammonium salt Into tricaprylylmethylammonium chloride or tributylethyl ammonium chloride. AMERICAN CYANAMID COMPANY Authorized Agent, ABSTRACT, A process for the preparation of anilino fumarates of formula IV is described; ro ₂ cch 'NK-C-CO ₂ R in which R is (C 1 -C 4) alkyl, which is carried out by reacting a compound of formula I: Cl - CH - CO ₂ R I Cl - CH - CO ₂ R wherein R is as defined above, with the mole equivalent of aniline in an inert organic solvent, such as a hydrocarbon, aromatic hydrocarbon, chlorinated aromatic hydrocarbon, aromatic hydrocarbon, or hydrocarbons thereof, said solvent being hydrochloric aromatic, aromatic hydrocarbon or mixtures thereof, and two or more molar equivalents of aqueous base such as 15 to 50% by weight of sodium, hydroxide, potassium hydroxide or mixtures thereof and in the presence of an intermediate phase catalyst such as quaternary ammonium salt consisting of such salts as which is N-butylammonium chloride, benzyltriethylammonium chloride or mixtures thereof at a temperature of about 20 ° C to about 90 ° C for 1 to 24 hours.