CH481091A - Process for the production of new keto acids - Google Patents

Description

  

  



  Process for the production of new keto acids
A benzofuran derivative has been isolated from the roots of water hemp (Eupatorium cannabinum), which is used for the treatment of liver diseases.



   Based on this observation, some cholagogues containing the benzofuran ring and the 2,3-dihydrobenzofuran ring have been prepared.



   The object of the present invention is a process for the preparation of keto acids of the following formula
EMI1.1
 in which R converts a group of the formula R'O- (IO-CH2-CH2-COC1 in which R 'denotes alkyl, and finally saponifies the ester formed.



   The aforementioned new products are useful medicines because of their remarkable cholagogue effects in animals and especially in humans.



   The following examples explain the implementation of the process according to the invention.



   Example I.
A) 7.4 g (0.05 mol) of 7-methoxybenzofuran in 75 cm5 of dry nitrobenzene are mixed with 5.5 g (0.055 mol) of succinic anhydride.
EMI1.2
 means.



   The ketobutyric acid chain is preferably bonded in the 4-position in the benzofuran derivatives and preferably in the 5-position in the coumaran derivatives.



   The new keto acids of the above formula are prepared according to the invention by reacting the corresponding methoxybenzofurans or methoxycumarans or 2-methylcoumaran in a solvent in the presence of a Friedel-Crafts reaction catalyst, such as aluminum chloride or tin tetrachloride, with succinic anhydride or in a solvent and in the presence of a catalyst of the Friedel -Crafts reaction, such as aluminum chloride or tin tetrachloride, with a monoester of succinic acid chloride of the formula
The mixture is cooled with an ice bath and 13.3 g (0.01 moles of aluminum chloride are added over 45 minutes.



   The solution is kept and stirred at room temperature for 24 hours. The complex is hydrolyzed with 20% hydrochloric acid while cooling; then the nitrobenzene is distilled off in a stream of steam. After decanting the water, the residue is dissolved with 10% sodium hydrogen carbonate, decolorized with charcoal, filtered and precipitated with 20% hydrochloric acid. The precipitate thus obtained is filtered off and recrystallized from dilute ethanol, 7-methoxybenzofuranoyl-4-propionic acid (melting point 160 to 1620 ° C.) being obtained.



   In a similar way, starting from 7-methoxy-2,3-dihydrobenzofuran, 7-methoxy-2,3-dihydrobenzofuranoyl-5-propionic acid is obtained.



   These acids can be converted into the corresponding salts with organic and inorganic bases using the usual methods.



   B) 7.4 g (0.05 mol) of 7-methoxybenzofuran in 35 cm3 of dry carbon disulfide are mixed with 8.2 g (0.05 mol) of carbethoxypropionyl chloride. The mixture is cooled to -100C; then 10 g (0.075 mol) of aluminum chloride are added in about 15 minutes. The whole is brought to room temperature and stirred for 1 hour. The complex is obtained with cooling with 20% thylcoumaranoyl) -5-propionic acid (melting point 130 to 131 ° C.). This acid can be converted into the corresponding salts using the usual methods with organic and inorganic bases.

 

Claims (1)

PATENT CLAIM Process for the preparation of new keto acids of the formula EMI2.1 wherein R hydrolyzes a group of the formula iger hydrochloric acid and extracts with chloroform, dried over dry calcium chloride and concentrated. An excess of alcoholic n / 2 potassium hydroxide solution is added to the oily residue and the mixture is refluxed on the water bath for one hour. The solution is evaporated to dryness, then the residue is dissolved in water, decolorized with charcoal, filtered and acidified with 20% hydrochloric acid. The precipitate obtained in this way is filtered off and recrystallized from dilute ethanol, 7-methoxybenzofuranoyl-4-propionic acid (melting point 160 to 162ob) being obtained. 7-Methoxy-2,3-dihydro-benzofuranoyl-5-propionic acid is obtained in a similar manner. These acids can be converted into the corresponding salts with organic and inorganic bases using the usual methods. Example 2 To a solution which contains 13.4 g of 2-methylcoumaran and 11 g of succinic anhydride in 100 cm3 of nitrobenzene and has cooled to OOC, 26.6 g of aluminum chloride are gradually added. The reaction mixture is stirred for 5 hours at 5 to 100 ° C., then one night at room temperature. The solution is poured into ice and hydrochloric acid, the solvent is distilled off in a stream of steam, the residue is cooled and the precipitate thus obtained is filtered off. Then it is dissolved in 8% sodium hydroxide solution, decolorized with bone charcoal and precipitated with 8% hydrochloric acid. The precipitate is filtered off, dried and recrystallized from benzene petroleum ether, (2-Me EMI2.2 means, characterized in that the corresponding methoxybenzofurans or methoxycumarans or the 2-methylcoumaran in a solvent in the presence of a catalyst of the Friedel-Crafts reaction either with succinic anhydride or with a monoester of succinic acid chloride of the formula R'O-CO-CH2- CH2-COCI in which R 'denotes alkyl, and in the latter case saponifies the ester obtained. UNDERCLAIMS 1. The method according to claim, characterized in that the ketobutyric acid chain is bound in the benzofuran derivatives in the 4-position and in the coumaran derivatives in the 5-position. 2. The method according to claim or dependent claim 1, characterized in that the new keto acids obtained are converted into the salts with organic or inorganic bases. 3. The method according to claim, characterized. that aluminum chloride or tin tetrachloride is used as a catalyst for the Friedel-Crafts reaction. 4. The method according to dependent claim 1, characterized in that aluminum chloride or tin tetrachloride is used as the catalyst for the Friedel-Crafts reaction.