HU208309B - Process for producing substituted benzoates - Google Patents

Abstract

The process of the present invention provides benzoic acid derivatives of formula (IV) wherein X is halogen, trifluoromethyl or nitro, n is 1, R3 and R4 are C1-C10 alkyl and R5 is hydrogen, by reacting a compound of formula (I) with a thioglycolic acid ester of the formula HS-CHR5COOR4 in the presence of a catalyst, wherein X, R3, R4 and R5 are as defined, and n is the above and Y is a leaving group. The compounds of formula (IV) are useful for the preparation of herbicidal agents. COOR3 £ CHR5C00R4 EN 208 309 B Description range: 8 pages (including 3 sheets)

Description

The present invention relates to a process for the preparation of substituted benzoic acid esters.

The substituted benzoic acid esters of the present invention are intermediates useful in the preparation of a herbicidal group of compounds, 2-benzoyl-1,3-cyclohexanediones. These herbicidal compounds and their benzoic acid derivatives - in which the benzoyl group may be replaced by one or more substituents such as one or more halogen, alkyl, halogenated alkyl, cyano, alkoxy, nitro or -SO ₂ R ² - and some form of substituted or unsubstituted

The preparation of 1,3-cyclohexanedione is described in U.S. Patent No. 4,780,127.

U.S. Patent No. 4,692,545 discloses the preparation of compounds of formula A wherein

X 'represents a chlorine atom or a nitro group and

R ¹ and R ¹ represent alkyl and are prepared by reacting a compound of formula B wherein X 'and R ¹ are reacted with alkyl-mercaptan of formula R-SH, wherein R is as defined above, in the presence of an inorganic base and a polar aprotic solvent.

U.S. Pat. No. 4,704,467 relates to the same reaction except that it is carried out in the presence of an inorganic base, a phase transfer catalyst and a non-polar aprotic solvent. The alkyl esters of 2- (chloro, bromo or nitro) -4-methylthiobenzoic acid are readily oxidized in the usual manner to the corresponding alkyl ester of 2-chloro-4-methylsulfonylbenzoic acid.

The esters of 2- (chloro, bromo or nitro) -4-methylthiobenzoic acid are converted to the corresponding benzoic acids in a known manner.

According to the invention, the herbicidal intermediates of formula I wherein X is halogen, trifluoromethyl or nitro, n is 1 and

^R5 is hydrogen, is prepared for the preparation of compound (IV) of the formula shown below.

1) A substituted benzoic acid derivative of formula (Π) is prepared or purchased in a known manner

X and n are as defined above and

Y is a leaving group such as nitro or halogen such as chlorine.

2) The substituted benzoic acid derivative of Step 1 is reacted with C 1-10 alkyl alcohol. The alcohol may be, for example, methanol, ethanol, butanol or isooctyl alcohol. Preferred alcohol is butanol. The reaction is preferably carried out in the presence of a catalyst, preferably an acid such as sulfuric acid, toluenesulfonic acid, hydrochloric acid or phosphoric acid or a Lewis acid such as aluminum trichloride or an ion exchange resin. The reaction may optionally be carried out in the presence of a solvent, for example alcohol may serve as a reaction solvent. If necessary, an auxiliary solvent may be used, suitable auxiliary solvents being solvents capable of removing water in an azeotropic form up to 140 ° C, such as toluene, xylene, monochlorobenzene or other hydrocarbon solvents.

3) The ester of formula (kapott) obtained in Step 2 - in the formula

X and Y are respectively reacted with thioglycolic acid ester of the formula HS-CHR ⁵ COOR ^{4 in} the presence of the above and R ^{3 is a} C 1 -C 10 alkyl group in which R ⁴ is a C 1 -C 10 alkyl group;

R ^{5 is a} hydrogen atom to give a diester of formula IV wherein X, R ³ , R ⁴ and R ⁵ are respectively n. Suitable bases are, for example, alkali metal carbonates or hydroxides, such as potassium carbonate, sodium carbonate, potassium hydroxide or sodium hydroxide. A preferred base is potassium carbonate.

Steps 1 and 2 above are optional, and in Step 3 any route or source can be used to prepare the ester.

Optionally, the ester of HSCHR ⁵ COOR ⁴ used in Step 3 may be prepared in situ from the corresponding acid in Step 2.

More particularly, the present invention relates to a process for the preparation of substituted benzoic acid derivatives of formula (IV) wherein:

X is halogen, trifluoromethyl or nitro, n is 1,

R ³ and R ^{4 are} C 1 -C 10 alkyl and R ⁵ is hydrogen, wherein the process is characterized in that an ester of formula (ΠΙ) wherein X, R ³ and n are as defined above and Y is a leaving group. with a thioglycolic acid ester of the formula HS-CHR ⁵ COOR ⁴ - wherein R ⁴ represents a C 1 -C 10 alkyl group and

R ^{5 in} the presence of a catalyst having the above meanings.

The novel process of the present invention is easily understood from the following reaction scheme, which is a

Illustrates the preparation of 2- (substituted benzoyl) -1,3-cyclohexanedione derivatives.

In Step 2, the substituted benzoic acid derivative can be esterified in a conventional manner. The alcohol has from 3 to 6 carbon atoms. Most preferably, the alcohol is n-butanol and the esterification reaction is carried out in the presence of a catalyst such as sulfuric acid. The reaction is preferably carried out at the boiling point of the reaction mixture by azeotropic removal of water until the reaction is complete. The reaction may be carried out in a solvent such as toluene, xylene, monochlorobenzene or other hydrocarbon solvents. However, alcohol may also serve as a solvent in the reaction. The ester reaction product can be recovered in the usual manner.

HU 208 309 Β

In Step 3, the leaving group of the 4-substituted benzoic acid ester is replaced by a thioglycolic acid ester as defined above. Preferably, n-butyl ester is used.

The reaction may be carried out in a non-aqueous medium in the presence of an inorganic base. Preferably, the base, when solid, is finely divided and preferably potassium hydroxide, potassium carbonate, sodium carbonate, sodium hydroxide, tricalcium phosphate or trisodium phosphate are used.

It comprises the two reagents in the non-aqueous medium without additional solvent.

When a solvent is required, an aprotic solvent is preferably used. Aprotic solvents do not have interchangeable hydrogen atoms, e.g. found in hydroxyl, mercaptan or amino groups.

If the aprotic solvent is polar, no phase transfer material is required; if non-polar, phase transfer material is required.

Non-polar, aprotic solvents include hydrocarbons such as benzene, toluene, xylenes, halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chlorobenzene, ethers such as tetrahydrofuran, diethyl ether, diisobutyl. ether and other non-polar aprotic solvents. Polar aprotic solvents include acetone, methyl ethyl ketone, acetonitrile, dimethylformamide, N-methylpyrrolidone, dimethylacetamide and methyl isobutyl ketone. Phase transfer catalysts are well known and include tris- (3,7-dioxaheptyl) amine (TDA-1), tricaprylylmethylammonium chloride (Aliquat 336), tetra- (lower alkyl) substituted ammonium, sulfonium and sulfoxonium halides, crown ethers and cryptans. Preferred examples are tetrabutylammonium bromide and tetraphenylphosphonium bromide.

The term "lower alkyl" includes C 1-6 alkyl groups.

If necessary, a two-phase system may be used, which is advantageous. In this system, a phase contains the two reagents and the desired product as prepared. This phase can be considered as a solvent. The other phase is an aqueous phase containing the dissolved inorganic base. In this system, a phase transfer catalyst is required to carry out the reaction.

The invention is illustrated by the following examples.

Example 1

Reaction equation 1

2-Chloro-4-nitrobenzoic acid (1000 g, 4.93 mol) was dissolved in butanol (747.0 g, 10.10 mol) and sulfuric acid (9.7 g, 0.10 mol) was added with stirring and the reaction mixture was stirred at room temperature. under reflux for 6 hours, when no more water is collected in the butanol-water separator.

The reaction mixture was allowed to cool to 50 ° C and washed with aqueous potassium carbonate solution (27.2 g, 0.2 molar potassium carbonate, 595 g water). The organic phase was separated and the solvent was distilled off under reduced pressure (13 kPa) at 125 ° C. The excess butanol was removed to give 1257.0 g of the desired butyl ester.

Example 2

Reaction equation 2

A mixture of the product of Example 1 (500.0 g, 1.84 mol), butyl thioglycolate (307.3 g, 1.97 mol) and tetrabutylammonium bromide (14.9 g, 0.05 mol) was stirred under stirring. A solution of potassium carbonate (288.0 g, 2.08 mol) in water (385 g) was added dropwise over 1 hour while maintaining the temperature below 30 ° C. The reaction mixture was stirred for an additional hour at room temperature, then heated to 50 ° C and stirred for an additional hour.

Water (250 g) was then added dropwise with stirring while maintaining the temperature at 50 ° C. The phases are then allowed to separate, and the organic phase is separated, washed with aqueous sulfuric acid (23.5 g, 0.24 molar sulfuric acid, 436 g water) and separated. 717.5 g of dibutyl ester are obtained.

Example 3

Reaction equation 3

2-Chloro-4-nitrobenzoic acid (200.0 g, 0.98 mol) was dissolved in toluene (520 g) and propanol (125.8 g, 2.1 mol). Sulfuric acid (2.6 g, 0.05 mol) was added and the reaction mixture was heated under reflux with Dean-Stark plug for 7 hours, when no more water collected in the toluene-water separator.

The reaction mixture was allowed to cool to room temperature and washed with aqueous sodium bicarbonate solution (69.0 g, 0.81 mol sodium bicarbonate, 620 g water). The organic layer was separated and azeotropically dried to give a toluene solution of the propyl ester.

Example 4

Reaction equation 4

To a solution of the product of Example 3 (267.7 g, 1.27 mol) in acetone (660 g) was added potassium carbonate (176.1 g, 1.27 mol) and the reaction mixture was heated to 55 ° C.

Then, 135.0 g (1.2 mol) of methyl thioglycolate were added at 55 ° C over 2 hours and the mixture was refluxed for 6 hours.

Acetone is distilled from the reaction mixture at a maximum temperature of 70 ° C. The residue was diluted with 770.0 g of toluene and 1500.0 g of water. The mixture was neutralized by addition of 25.0 g (0.25 mol) of sulfuric acid, warmed to 50 ° C and allowed to separate.

The organic phase was separated to give a solution of the diester product in toluene.

Example 5

Reaction equation 5

108.7 g of toluene and 26.5 g (0.045 mol) of propanol are dissolved in 20.0 g (0.1 mol) of 2-chloro-4-nitrobenzoic acid and 10.1 g (0.1 mol) of thioglycolic acid. To the reaction mixture was added 15.0 g of Amberlyst A15 resin and refluxed for 30 hours with a Dean-Stark plug.

EN 208 309 Β under reflux until no more water accumulates in the toluene-water separator.

The reaction mixture was allowed to cool to room temperature and washed with aqueous sodium bicarbonate solution (3.5 g sodium bicarbonate, 100 g water). The organic phase was separated and dried by azeotropic drying.

Example 6

Reaction equation 6

2-Chloro-4-nitrobenzoic acid (40.0 g, 0.2 mol) and thioglycolic acid (21.9 g, 0.24 mol) were dissolved in 183.1 g (2.47 mol) of butanol. 20.7 g (0.11 mol) of p-toluenesulfonic acid are added and the reaction mixture is refluxed for 24 hours under a Dean-Stark plug until no more water is collected in the butanol-water separator.

The reaction mixture was then washed with aqueous sodium bicarbonate solution (9.2 g sodium bicarbonate, 150 g water) and water (2 x 100 g). The organic layer was separated and azeotropically dried to give a solution of the butyl ester of step 2 and butyl thioglycolate.

Example 7

Reaction equation 7

A sample of the product of Example 5 was removed under reduced pressure to give a mixture of propyl esters, the propyl ester of step 2 (about 0.05 mol) and propyl thioglycolate (about 0.055 mol).

The residue was taken up in 75 ml of acetone, heated to 55 ° C and 7.59 g (0.055 mol) of potassium carbonate was added and the reaction mixture was stirred at 55 ° C for 5 hours.

Toluene (75 mL) was added to the reaction mixture and acetone was removed by distillation under reduced pressure. The reaction mixture was diluted with 80 g of water, neutralized with 46 ml of hydrochloric acid and the organic phase was separated. A toluene solution of the dipropyl ester is thus obtained.

Example 8

Reaction equation 8

A sample of the product of Example 6 was removed under reduced pressure to give a mixture of the butyl ester of step 2 (about 0.05 mole) and butyl thioglycolate (about 0.05 mole).

The residue is taken up in 50 ml of acetone, warmed to 55 ° C and potassium carbonate (7.6 g, 0.055 mol) is added. The reaction mixture was stirred for 5 hours at 55 ° C.

Toluene (75 mL) was added to the reaction mixture and acetone was removed by distillation under reduced pressure. The reaction mixture was diluted with 80 g of water and neutralized with 46 ml of hydrochloric acid. The organic phase was separated to give a solution of the dibutyl ester in toluene.

Example 9

Reaction equation 9

To a solution of the product of Example 1 in toluene (40 mL, containing 0.05 mol of product) at 50 ° C was added 7.6 g (0.055 mol, of high purity) potassium carbonate and 0.005 mol of phase transfer catalyst.

To the reaction mixture was added methyl thioglycolate (5.8 g, 0.055 mol), the temperature was raised to 55 ° C, and the mixture was stirred for 5 hours.

It is then diluted with 80 g of water and neutralized with 46 ml of hydrochloric acid. The organic phase was separated to give a toluene solution of the product.

The reaction was carried out with the following phase transfer catalysts:

tris (3,7-dioxaheptyl) amine (1.6 g),

Me ₄ NBr (0.77 g), benzyl triethylammonium bromide (1.1 g),

C ₁₆ H 34 Bu ₃ PBr (2.5 g), tetrabutylphosphonium bromide (1.7 g), tetraphenylphosphonium bromide (2.1 g).

Example 10

Reaction equation 10

To a solution of propyl 2,4-dichlorobenzoate (5.0 g, 0.02 mol) in dimethylformamide (40 ml) was added potassium carbonate (3.1 g, 0.22 mol) and the mixture was heated to 50 ° C. A solution of 2.4 g (0.044 mol) of methyl thioglycolate in 5 ml of dimethylformamide was added and the mixture was stirred for 10 hours at 50 ° C and then for 5 hours at 100 ° C.

The mixture was allowed to cool, diluted with 100 g water and extracted with toluene. The toluene layers were combined and the solvent removed in vacuo.

The residue was chromatographed on silica gel (eluent: ethyl acetate-petroleum 1: 8) to give 2.0 g of product.

Claims (1)

A process for the preparation of substituted benzoic acid derivatives of formula IV wherein X is halogen, trifluoromethyl or nitro, n is 1, R ³ and R ^{4 are} C 1 -C 10 alkyl and R ⁵ is hydrogen, characterized in that an ester of formula (III) X and R ³ , respectively, and n are as defined above and Y is a leaving group with thioglycolic acid ester of the formulaHS-CHR ⁵ COOR ⁴ , wherein R ⁴ and R ^{5 are in} the presence of a catalyst as defined above.