DE582715C - Process for the preparation of 4-butylaminobenzoic acid ª ‰ -dimethylaminoaethyl ester - Google Patents

Description

GERMAN EMPIRE

BibUofheek Bur. Ina. EigendoSi

12 SEP. 1933

ISSUED ON
AUGUST 21, 1933

REICH PATENT OFFICE

PATENT LETTERING

M 582715 CLASS 12q GROUP

I. G. Farbenindustrie Akt.-Ges. in Frankfurt a. M. *)

It has been found that esterifying 4-butylaminobenzoic acid with / J-dimethylaminoethanol or others 4-Butylaminobenzoic acid - /? - dimethylaminoethyl ester is the usual method for the preparation of esters obtained as such and in the form of its water-soluble salts, e.g. B. the monohydrochloride by has a very strong anesthetic effect

ίο complete lack of irritation and a very cheap one therapeutic index and therefore not only for surface anesthesia, but 'also seems particularly suitable for conduction, lumbai and sacral anesthesia.

'The product of the process can also be carried out by

. Treatment of the 4-aminobenzoic acid / I-dimethylaminoethyl ester be represented with butylating agents. ~~

example 1

4-Butylaminobenzoic acid is obtained by boiling an aqueous solution of sodium 4-aminobenzoic acid with n-butyl bromide. It is a colorless crystalline powder with a melting point of 153 to 154 ⁰ .

Equimolecular amounts of 4-butylaminobenzoic acid and hydrochloric acid-ß-dimethylaminoethanol are suspended in ten times the amount by weight of toluene, the mixture is saturated with hydrochloric acid gas and heated in an oil bath at about 150 ° while passing through a very slow stream of hydrochloric acid so that toluene slowly distills over. With this, the water produced during the esterification passes over. After heating for about an hour, water is added to the cooled mixture until the salt has dissolved, the toluene layer is separated off, and the ester base is precipitated from the aqueous solution with sodium carbonate solution. By receiving the base in ether, drying the separated ether solution over potassium carbonate and adding the same with alcoholic hydrochloric acid to the reaction lackmusneutralen the monohydrochloride is deposited as a colorless crystalline powder, which was recrystallized from alcohol at 147-148 ⁰ melts.

The 4-butylaminobenzoic acid / 3-dilnethylaminoethyl ester monohydrochloride is a colorless crystal powder, easily soluble in water. The solution is without the risk of decomposition sterilizable by boiling. That from the aqueous solution of the salt with sodium hydroxide solution (oily at first, but solidifying quickly), precipitable base forms colorless crystals and

*) The patent seeker stated as the inventor:

Dr. Otio Eisleb in Hofheim, Taunus.

melts at 43 ⁰ . The Fikrat melts at 120 °. With oxalic acid, the base forms a neutral oxalate that is easily soluble in water and an acidic oxalate that is very poorly soluble in cold water.

Example

Ethyl 4-butylaminobenzoate is best prepared from 4-butylaminobenzoic acid and four times the weight of alcohol containing ι * / ₃ mol of hydrogen chloride by refluxing, partially distilling off the alcohol and breaking it down with sodium hydroxide solution. It forms colorless crystals and melts at 69 to 70 ⁰ .

If ethyl 4-butylaminobenzoate is boiled with excess /? - dimethylaminoethanol with the addition of a little sodium ethyl ether, alkyl displacement occurs: ethyl alcohol is distilled over; after the excess ¹ of Dimethylaminoäthanols is distilled off in vacuo, the remaining 4-Butylaminobenzoesäure-jS-dimethylaminoäthylester is converted with the equimolecular amount of alcoholic hydrochloric acid in the monohydrochloride which to 148 ⁰ precipitates in crystals melting at 147 by cooling the solution.

Example 3

4-Butylaminobenzoic acid yS-chloroethyl ester is made by saturating a solution of 4-butylaminobenzoic acid in ten times the amount Ethylene chlorohydrin with hydrochloric acid gas, heating the mixture on the Water bath and subsequent distillation of the ethylene chlorohydrin excess in Maintain vacuum. The oily crude ester is purified by being absorbed in ether and washing acid-free with sodium carbonate solution, drying over potassium carbonate and distilling off the ether.

4-butylaminobenzoic acid / I-chloroethyl ester is cooled in a benzene solution

45. of slightly more than the calculated amount • dissolved of dimethylamine; this solution will Heated to 100 ° in a pressure vessel for 5 hours. After cooling, the benzene solution becomes shaken out several times with water, whereby the dimethylamine salt is dissolved in the water, but the ester base remains in the benzene layer. The ester base becomes the benzene layer removed by shaking with dilute acetic acid; from the separated acetic acid Solution, the base is precipitated with sodium hydroxide solution, taken up in ether and dried over sodium carbonate. the ethereal solution gives in cases with alcoholic hydrochloric acid up to the litmus-neutral Reaction the 4-butylaminobenzoic acid / I-dimethylaminoethyl ester monohydrochloride from 147 to 148 °.

Example 4 '

Equimolecular amounts of 4-aminobenzoic acid / 5-dimethylaminoethyl ester and n-butyl bromide are refluxed for 3 hours in an oil bath with the addition of butyl alcohol as a diluent. It 'is added to hot water and butyl ₇ "distilled alcohol with water vapor. After cooling, the aqueous solution is precipitated with sodium carbonate solution, the alkamine ester mixture is taken up in ether, dried over potassium carbonate and, after the ether has been distilled off, fractionated in vacuo. The 4-Butylaminobenzoesäure- / i-dimethylaminoäthylester proceeds at 4 mm pressure to 210 ^0th For complete cleaning is prepared in alcoholic solution the monohydrochloride, which melts at 147-148 ^0th

Claims (1)

Claim: Process for the preparation of 4-butylaminobenzoic acid dimethylaminoethyl ester, characterized in that 4-butylaminobenzoic acid is converted into the β-dimethylaminoethyl ester by customary methods transferred or 4-aminobenzoic acid / S-dimethylaminoethyl ester treated with butylating agents.