DE1055541B - Process for the preparation of beta-dialkylaminoacylanilides - Google Patents

Description

GERMAN

The present invention relates to a process for the preparation of substances which may be substituted in the benzene ring yS-Dialkylammo-acylanihden

These compounds have valuable pharmacological properties Properties, including as anesthetics, especially for nerve-blocking anesthesia, and are described in part in patent 949 235

It has now been found that it is possible, if necessary / 3-Monoalkylammoacylamlides substituted in the benzene ring and / 3-Piperidmo-acylanilide with unsubstituted Phenyl group by reduction from the corresponding Immo compounds or their tautomeric Forms to manufacture the / J-alkylimmoacylanilides can namely also as 2-alkylammo-acylanihde unsaturated in the 1,2-position The corresponding compounds with the / 3-position pipendmo group are located naturally only in the latter form

In the Ber dtsch. Ehern Ges, 27 (1892), S 771, and in the Annalen der Chemie, 439 (1924), p. 213, is the Production of jS-Immo-buttersaureamlid or the with it tautomeric ß-Ammo-crotonsaureanihds by reaction of Acetoessigsaureanihd with Ammen described from It is clear from these publications that the Reaction product decomposes extremely easily and when boiling m aqueous solution or even when dissolving of the hydrochloride in water at room temperature is quickly and quantitatively converted back into the corresponding Amm and the acetoacetic acid anhydride

Under these circumstances it was not foreseeable that it would be possible to make connections to the above specified type with satisfactory yield to the corresponding saturated monoalkylammo- or piperidino compounds to reduce

In fact, attempts hitherto have been made to carry out this reduction, for example by Hydrogenation, in general, give very low yields. Surprisingly, it has been found that it this reduction is possible when using aluminum amalgam to be carried out with a relatively good yield

The invention therefore relates to a method of production of / 5-dialkylammoacylamlides of the general formula

R ₁ -CH-CH ₂ -CO-NH-R

τ? p

worm R is an optionally substituted phenyl group, R _{1 is} a hydrocarbon residue, ζ Β is an alkyl group, R ₂ and R _{3 are} alkyl groups or, together with the nitrogen atom, a piperidmo group, in the latter case the phenyl group is not substituted, in which one corresponding immoacylanilide or their

Method of manufacture
of ß-dialkylammoacylanilides

Applicant:

Ed. Spiritual sons A. G.

for chemical industry,

Wolhusen, Lucerne (Switzerland)

Representation Di F Zumstem
and Dipl -Chem Dr rer nat E Assmann,

Patent attorneys,
Munich 2, Brauhausstr 4

Claimed priority
Great Britain from November 1, 1954

Emil Hofstetter, Wolhusen, Lucerne (Switzerland),
has been named as the inventor

tautomeric forms are reduced with aluminum amalgam and, if R _{2 is} hydrogen, then the alkyl group R ₃ m is introduced in a manner known per se

It is advantageous to do the reduction in an organic and preferably in an alcoholic solvent Methanol is the preferred solvent It is also useful to adjust the temperature as low as possible, preferably at room temperature, to keep

The reduction takes some to complete Time during which the reaction mixture is preferred is continuously stirred or shaken to Ensure thorough mixing. After completion, the reduction product in the solvent layer can be used separated off, freed from the solvent, for example by evaporation in vacuo, and can be worked up in any way.

As substituents m of the phenyl group as starting materials used / 3-monoalkylimmo-acylamlides For example, alkyl, alkoxy, nitro and amino groups and halogens come into consideration. The alkyl radicals the dialkylamino group of the final product are preferred Methyl or ethyl groups

When the substituent in the ring, e.g. B a nitro group, is itself reducible, it can in the inventive Procedures are of course reduced

VS '. 2 '' 909 507/556

example 1
a) Production of / J-ethylamino-butyric anilide

50 g / 5-ethylammocrotonic acid anilide are used in Dissolved 450 ecm of methanol and then mixed with 40 g of the aluminum amalgam prepared as described below. The mixture is stirred for 35 hours at room temperature. The methanolic solution is separated off, filtered and the methanol evaporated in vacuo. ' A viscous oil remains, / I-ethylamino-butyric anilide. Yield 40 g (70.9% of theory).

The aluminum amalgam as used herein, is freshly prepared from aluminum shavings, once, twice with N / 10 sodium hydroxide solution, with water, twice with a liter ° / _o solution of mercury (II) chloride and washed once with water.

b) Production of /3-Diäthylam.ino-butyeanilid

70 g of ß-ethylamino-butyric anilide are used in 40 g of ethyl bromide and 10 ecm of alcohol dissolved and boiled for 72 hours. Then the reaction mass in Dissolved excess 2N hydrochloric acid, filtered and made alkaline. The precipitated substance is taken up in ether and dried well. Dry hydrogen chloride is passed into the dry ether solution, whereby the hydrochloride of ß-diethylamino-butyric acid anilioUi fails. It melts at 132 to 134 ° C and is easily soluble in water.

Example 2

30th

10 g of ß-piperidino-crotonic acid anilide are dissolved in 250 ecm of ether and 250 ecm of alcohol (90 ° / ₀ ig) and mixed with 10 g of aluminum amalgam. After stirring for 30 to 40 hours at room temperature, the precipitate is separated off and the clear solution is concentrated. The residue is dissolved in ethyl acetate and hydrogen chloride is passed in, the hydrochloride of 3-piperidinobutyric anilide precipitating out.
Yield 5 g (43 ° / ₀ ). M.p. 209 to 212 ° C.

Claims (3)

Patent claims: 1. Process for the preparation of / 9-dialkylaminoacylanilides the general formula R ₁ -CH-CH ₂ -CO-NH-R , N, ■ R » wherein R is an optionally substituted phenyl group, R _{1 is} a hydrocarbon radical, e.g. B. denote an alkyl group, R ₂ and R ₃ alkyl groups or together with the nitrogen atom a piperidino group, the phenyl group being unsubstituted in the latter case, characterized in that corresponding iminoacylanilides or their tautomeric forms are reduced with aluminum amalgam and, if R ₂ Is hydrogen, then introduces the alkyl group R ₃ in a manner known per se. 2. The method according to claim 1, characterized in that the reduction in alcoholic Solution carried out at room temperature with shaking or stirring. 3. The method according to claim 1 or 2, characterized in that one / J-ethylamino-crotonic acid anilide or ß-piperidino-crotonic acid anilide as starting material used. © 909 507/556 4.59