DE2318566C3 - 3-alkoxy-5-substituted phenylacetic acids - Google Patents

Description

The first method of preparing (1) is to hydrolyze a compound of the general formula

OR,

(H)

CH ₂ R ₃

in which R ₁ and R 2 are as defined above and R _{3 is} an alkoxycarbonyl or cyano group. , ₅

It is advantageous to carry out the reaction in the presence of methanol when carrying out this process and sodium hydroxide or in the presence of acetic acid and sulfuric acid.

Another preferred method is the reduction of the corresponding halogen-substituted compounds. This second method of representation (1) consists in the reduction of a compound of the general formula

(111)

CH ₂ COOH

the methanol was removed and the aqueous solution that remained was washed with ether and acidified by adding dilute hydrochloric acid. The crystal precipitate was filtered off, washed with water and dried and recrystallized from ethanol / water. There were 37 g 3 - Methoxy - 5 - (phenyl) phenylacetic acid with a melting point of 141 to 143 ° C. was obtained. The other Recrystallization gave crystals with a melting point of 143 to 144 ° C.

Analysis for C ₁₅ H ₁₄ O ₃ :

Calculated ... C 74.36, H 5.83%;
found .... C 74.65, H 5.69%.

b) 4.5 ml of a mixture of concentrated sulfuric acid, acetic acid and water in equal parts was added to 1.4 g of 3-methoxy-5- (phenyl) phenyl acetonitrile and the mixture was left on for 12 hours heated to 90 ° C. in an oil bath with stirring. The crystal precipitate was filtered off and washed with water and dried and recrystallized from ethanol / water. There were 0.7 g of 3-methoxy-5- (phenyl) phenylacetic acid (Melting point 143 to 144 C).

Example 2

This example explains a method of representation of 3-methoxy-5-isopropyl-phenylacetic acid of the following formula

in which R _{4 is} a halogen-substituted alkoxyphenyl group or a halogen-substituted thienyl group and R _{2 has} the meaning given above. In this second method, the reduction can be done in a number of ways. Reduction is preferably carried out catalytically, in particular using palladium-carbon.

The invention is explained in detail below by means of examples. Examples 1 to 10 relate to the first method, namely hydrolysis, and Examples 11 and 12 to the Reduction process.

45

example 1

This example illustrates a method for preparing 3-methoxy-5- (phenyl) phenylacetic acid the following formula

OCH ₃

CH ₂ COOH

55

60

a) A solution of 9.2 g of sodium hydroxide in 120 ml of water became 56.4 g of methyl 3-methoxy-5- (phenyl) phenyl acetate added and the mixture was further treated with 120 ml of methanol. Then the mixture was allowed to form a homogeneous solution heated. After 30 minutes to 1 hour heated

A solution of 1.05 g of sodium hydroxide in 20 ml of water became 5.3 g of methyl W-methoxy-S-isopropylphenyl acetate added. Furthermore, 20 ml of methanol were added, after which the mixture to form a homogeneous solution was heated.

After heating for 30 minutes to 1 hour, the methanol was distilled off, the remaining aqueous solution washed with ether and acidified by adding dilute hydrochloric acid. The precipitated oily substance was extracted with ether.

The ether extract was washed with water and dried, and the ether was distilled off. the The residue was distilled under reduced pressure. 2.7 g of S-meloxy-S-isopropyl-phenylacetic acid were obtained (Boiling point 150 to 152 C at 4 mm Hg) (melting point 40 to 43 C).

Analysis for C ₁₂ H ₁₁₁ O,:

Calculated ... C 69.21. H 7.74%:
found .... C 68.98. H 8.01%.

In a similar manner, the following compounds were made receive.

The first method of preparing (1) is to hydrolyze a compound of the general formula

OR,

(H)

CH ₂ R ₃

in which R ₁ and R _{2 have} the meaning given above and R _{3 is} an alkoxycarbonyl or cyano group. i _S

It is advantageous to carry out the reaction in the presence of methanol when carrying out this process and sodium hydroxide or in the presence of acetic acid and sulfuric acid.

Another preferred method is the reduction of the corresponding halogen-substituted compounds. This second method of representation (1) consists in the reduction of a compound of the general formula

OR,

(HI)

CH ₂ COOH

had been, the methanol was distilled off, the remaining aqueous solution washed with ether and acidified by adding dilute hydrochloric acid. The crystal precipitate was filtered off, washed with water and dried and recrystallized from ethanol / water. There were 37 g of 3 - methoxy - 5 - (phenyl) phenylacetic acid obtained with the melting point 141 to 143 ⁰ C. Further Urakristallisierung gave crystals of melting point 143-144 ⁰ C.

Analysis for C ₁₅ H ₁₄ O ₃ :

Calculated ... C 74.36, H 5.83%;
found C 74.65, H 5.69%.

b) 4.5 ml of a mixture of concentrated sulfuric acid, acetic acid and water in equal parts was added to 1.4 g of 3-methoxy-5- (phenyl) phenylacetonitrile and the mixture was left on for 12 hours heated to 90 ° C. in an oil bath with stirring. The crystal precipitate was filtered off, washed with water and dried and, from ethanol, water umkrir.tallisiert. There were 0.7 g of 3-methoxy-5- (phenyl) phenylacetic acid (Melting point 143 to 144 C).

Example 2

This example illustrates a method for preparing 3-methoxy-5-isopropyl-phenyl acetic acid the following formula

in which R _{4 is} a halogen-substituted alkoxyphenyl group or a halogen-substituted thienyl group 3s and R _{2 has} the meaning given above. In this second method, the reduction can be done in a number of ways. Reduction is preferably carried out catalytically, in particular using palladium-carbon.

The invention is explained in detail below by means of examples. Examples 1 to 10 relate to the first method, namely hydrolysis, and the examples and 12 to that Reduction process.

example 1

This example illustrates a method for preparing 3-methoxy-5- (phenyl) phenylacetic acid the following formula

OCH ₃

55

CH ₂ COOH

a) A solution of 9.2 g of sodium hydroxide in 120 ml of water became 56.4 g of methyl 3-methoxy-5- (phenyl) phenyl acetate added and the mixture was further treated with 120 ml of methanol. Then the mixture was allowed to form a homogeneous solution prhii7t. After 30 minutes to 1 hour heated

CH ₂ COOH

A solution of 1.05 g of sodium hydroxide in 20 ml of water was added to 5.3 g of methyl ^ -methoxy-S-isopropylphenyl acetate added. Furthermore, 20 ml of methanol were added, after which the mixture to form a homogeneous solution was heated.

After heating for 30 minutes to 1 hour, the methanol was distilled off, the remaining aqueous solution washed with ether and acidified by adding dilute hydrochloric acid. The precipitated oily substance was extracted with ether.

The ether extract was washed with water and dried, and the ether was distilled off. the The residue was distilled under reduced pressure. There were 2.7 g of S-methoxy-S-isopropyl-phenylacetic acid (Boiling point 150 to 152 C at 4 mm Hg) (melting point 40 to 43 C).

Analysis for C ₁₂ H ₁₁₁ O ₃ :

Calculated ... C 69.21, H 7.74%:
rounded .... C 68.9 «. H 8.01%.

In the same manner, the following compounds were obtained.

Examples 3 to 10

Representation of compounds of the following formula:

CH ₁ COOH

At- R, R,

Methyl n-butyl

Methyl isobutyl

Cyclohexyl methyl

Boiling point or melting point

o-chloro-

phenyl

p-chloro-

phenyl

2-thienyl

p-methoxy

phenyl

p-tolyl

methyl
methyl

methyl
methyl

M.p. 60 to 61 C m.p. 98 to 99 C b.p. 186 to 190 C (3 mm Hg)
M.p. 49 to 53 C bp. 210 to 213 C (1 mm Hg)
M.p. 149-152 ° C

M.p. 124 to 127 C. M.p. 142 to 144 C

Methyl m.p. 134 bis! 38 C acetic acid of the folaenaen formula
OCH,

Example U

This example illustrates a method for preparing S-methoxy-Sp-methoxyphenyl-phenyl-CH _{1 COOII}

H ₁ CO

3.8 g of 3-methoxy-5- (p-methoxy-m- or o-bromo) -phenyl-phenylacetic acid were dissolved in 200 ml of acetic acid, and 1.0 g of sodium acetate was added to the solution. The catalytic reduction was carried out at room temperature under atmospheric pressure in the presence of a palladium-carbon catalyst. 2.8 g of S-methoxy-Sp-methoxyphenylphenyl acetic acid (melting point J42 to J 44 "C) were obtained.
Analysis for C ₁₆ H ₁₆ O ₄ :

Calculated ... C70.57, H 5.92%;

found .... C 70.50, H 5.87%.

The following compound can be synthesized in the manner described above:

At- R.,
game

No.

Melting point

12 2-thienyl methyl 124-127 ° C