DE228667C - - Google Patents

Description

IMPERIAL

PATENT OFFICE.

The main patent relates, among other things, to a process for the preparation of amides the ß-ß-dialkylated propionic acids (with the exception of isovaleric acid and methylethylpropionic acid), that consists in converting these substituted propionic acids into their amides.

It has now been found that the therapeutically valuable amides can also be used after Can obtain cyanoacetic ester synthesis. For this purpose, the halides of the corresponding dialkyl carbinols are mixed with alkali metal cyanogen acetate treats the so available

A.

CiV
\ /H

c (

11 \ | iVfl + halogen- ₍
COOR

CN

\ HH, R ₁ C cζ + H ₂ SO ₄

COOH

Dialkylcarbincyanessigester saponified and by the action of concentrated sulfuric acid and carbon dioxide cleavage converted into the acid amide. Part of that process can also be carried out in one operation by taking the dialkylcarbincyanoacetate heated directly with concentrated sulfuric acid, with saponification, amide formation and Carbonic acid separation takes place in one operation; or you can saponification, carbonic acid elimination and cause amide formation in a different order. The procedure is z. B. according to the following schemes:

CN \ HH, R ₁ C C <

I \ R

COOR

CONH,

and after CO ₂ - Spin-off: 55

60

R ₁

CH

CH _Z

CONH ₂ .

Claims (1)

H ₂ SO, CN \ HH / R ₁ B. C C ( I \ ä ₂ COOR CONH ₂ \ HH / R ₁ C C ¹ / \ COO \ H Example. 113 parts of cyanoacetic ester are mixed with 200 parts of absolute alcohol and a sodium ethylate solution (23 Na in 230.0 alcohol) is allowed to run into this mixture. 15 parts of methylpropylcarbinol bromide are then added and the mixture is refluxed until the reaction is neutral. The alcohol is then distilled off, water is added to the residue and the oily methylpropylcarbincyanoacetate is siphoned off. Boiling point of the pure ester 175 ⁰ at 25 mm. The methylpropylcarbincyanoacetic acid ester is then saponified with the calculated amount of alcoholic sodium hydroxide solution, the sodium salt is dissolved in water and the free methylpropylcarbincyanacetic acid is separated off by adding dilute sulfuric acid. This acid, in its raw state, is _{heated for several hours with 1Y 2} times the amount of concentrated sulfuric acid and a fourth part of its weight of water. After pouring into iced water, the Methylpropylcarbinmalaminsäure separates out, which was heated to i8o °, splits off carbon dioxide and passes into the Methylpropylpropionsäureamid of melting point 99 ^0th You can also use the methylpropylcarbine CONH ₂ Ii?
C. I.
COOR R ₁ CH
I.
CH, CONH ₉ . Heat cyanoacetic ester with i ^x / ₂ times the amount of concentrated sulfuric acid with the addition of a little water, saponify the resulting malamic acid ester with aqueous sodium hydroxide solution and convert the methylpropylcarbinomalamic acid obtained in this way into the methylpropylpropionic acid amide by splitting off carbon dioxide. The ß-ß-diethylpropionic acid amide or other of the amides mentioned can be analogous Way to represent. Likewise, instead of the bromide in the above example, others can be used Use carbinol halides without changing the nature of the reaction. * Pa τ ε ν τ - A ν s ρ r υ c η: Modification ■ of the method for the representation of the Amides of ß-ß-dialkylated propionic acids (with the exception of isovaleric acid and the methylethylpropionic acid), consisting in the fact that the halides of the corresponding dialkylcarbin oils with alkali metal cyanetyl esters condensed and the products thus obtainable saponified in any order, converted into the amide and splits off carbonic acid from them.