DE608412C - Process for the preparation of derivatives of di- or trimethoxy- or -aethoxybenzoic acids - Google Patents

Description

Process for the preparation of derivatives of the di- or trimethoxy or Ethoxybenzoic acids It has been found that the dimethyl or diethvlamide of the di- or trimethoxy or -ätholybenzoic acids valuable therapeutic properties by having an effect on the circulation and breathing. For the Dialhylamides of benzoic acid and ethoxybenzoic acid have already reached 1 t h a u (Archive for Experimental Pathology and Pharmacology 36 [i895], p. 46o} and H a r r a s (Archives Internationales de Pharmacodynamie et deTherapie Il [19o3), 443 and 444) found an exciting effect on the respiratory center. Both dialkylamides of the di- or trimethoxy- or -ethoxybenzoic acids this exciting effect is much more pronounced. Such an increase in effectiveness could not be foreseen.

The preparation of derivatives of the di- or trimethoxy- or -äthoxybenzoesäuren carried out by conversion of these acids in the customary manner into their dimethyl or Diäthylamide, most easily by treatment of halides of the acids with the lung Dialkw lamins.

Example i 10.1 parts of veratroyl chloride are dissolved in 400 parts of absolute ether and poured into a solution of 29.3 parts of diethylamine in 100 parts of absolute ether. Diethylamine hydrochloride precipitates and is separated off after a few hours. After the ether has evaporated, the remaining oil is distilled in vacuo. For further purification, the distillate is dissolved in a little water, precipitated by adding potash, taken up in ether and, after drying over potash, distilled again in vacuo, the veratrumsäurediäthylamid passes under a pressure of 12 mm at 2o5 '.

Examples 20 parts of veratroyl chloride are dissolved in 300 parts of toluene and poured into a solution of 9 parts of dimethylamine in 150 parts of toluene. Dimethylamine hydrochloride precipitates and is separated off after a few hours. After the toluene has been distilled off, the residue is distilled in vacuo. The Veratrumsäuredimethylamid distilled over under a pressure of 12 mm at 203 ° as a colorless oil, which immediately solidified. After recrystallization from petroleum ether, it is obtained in the form of colorless, glossy crystal needles which melt at 102 to 1o3 °. Example 3 51 parts of 3, 4, -5-trimethoxybenzoyl chloride (Journ.Chem.Soc.89 [rgo6], p.1655) are dissolved in 150 parts of toluene and poured into a solution of 20 parts of dimethylamine in zoo parts of toluene. After standing for a while, the precipitated dirnethylamine hydrochloride is separated off and washed with toluene. After the toluene has been distilled off, the residue is distilled in vacuo. The 3, 4, 5-trimethoxybenzoic acid dimethylamide goes over under a pressure of 13 mm at 218 ° and crystallizes in the template. It is expediently recrystallized from ether, whereby it is obtained in colorless crystal needles which melt at b74 °. Example 4 A solution of 54 parts of 3,4,5-trimethoxybenzoyl chloride in 150 parts of benzene is poured into a solution of 35 parts of diethylamine in 60 parts of benzene for 15 minutes. After standing for a while, the precipitated diethylamine hydrochloride is separated off, washed with benzene and the benzene solution is evaporated. The residue boils at a pressure of 13 mm between 22o and 226 ° and slowly solidifies in a crystalline manner. Recrystallized from warm petroleum ether, the 3, 4, 5-trimethoxybenzoic acid ethylamide is obtained in the form of white needles which melt at 54 °. .

", 'Example 5 4o parts 2, 3-dimethoxybenzoyl chloride, prepared by Action of thionyl chloride on 2,3-dimethoxybenzoic acid (Journ. Chem. Soc. 123 [1923], p. 1575) are dissolved in 20 parts of toluene and with a little more than that calculated amount of dimethylamine, dissolved in 400 parts of toluene, with ice cooling and after displaced. After standing for several hours at room temperature, dimethylamine hydrochloride is used filtered off and the toluene was distilled off under reduced pressure. The amide lasts minor impurities stubbornly back. To remove it, it will be in water dissolved, the solution treated with animal charcoal and the filtrate evaporated in vacuo. e The 2,3-dimethoxybenzoic acid dimethylamide boils at 12 mm at 172 ° and represents a colorless, viscous oil, which is miscible with water and is in Alcohol, ether, benzene easily dissolves.

Example 6 3-methoxy-4,5-diethoxybenzoyl chloride, prepared from the 3-methyl ether of gallic aldehyde obtained by the process of patent 53o 65o by alkylation with diethyl sulfate, oxidation of the product obtained with potassium permanganate and action of thionyl chloride on the resulting 3-methoxy-4, 5-diethoxybenzoic acid, is mixed with 2 mol of diethylamine in an ethereal solution, with almost quantitative Yield the amide is obtained. 3-Methoxy-4,5-diethoxybenzoic acid diethylamide boils under 12 mm pressure at 211 to 2i2 °; it represents a pale yellowish, thick Liquid, which is easily soluble in water and the common organic Solvents is.

Example? The 3,5-dimethoxy-4-ethoxybenzoyl chloride obtained by the action of thionyl chloride on 3,5-dimethoxy-4-ethoxybenzoic acid (Am. 50C. 41 [1919], p. 8o1), and diethylamine 3, 5- DimethOxy-4 = ethoxybenzoic acid diethylamide is a viscous oil which boils at 213 'under 13 mm pressure.

Claims (1)

PATENT CLAIM: Process for the preparation of derivatives of the di- or Trimethoxy- or ethoxybenzoic acids, characterized in that these acids converted in the usual way into their dimethyl or diethylamides.