DE935546C - Process for the preparation of N-acyl derivatives of iminodibenzyl - Google Patents

Description

Process for the preparation of N-acyl derivatives of iminodibenzyl N-acyl derivatives of iminodibenzyl have not yet become known. According to the invention, they are now prepared by reacting compounds of the general formula in which n is an integer from z to 3 and Hal is a halogen atom, with dialkylamines, trialkylenediamines or alkylenimines containing 5 to 6 ring members containing low molecular weight alkyl groups in a manner known per se.

The N-acyl derivatives of iminodibenzyl produced in this way are strong Local anesthetic and partly also spasmolytic effectiveness. Because of their alkali resistance they can also be used as local anesthetics together with alkaline-reacting drugs come into use.

The reaction is preferably carried out in an inert organic solvent, z. B. benzene or its homologues made; but it can go higher boiling Amines can also be carried out without a solvent. To bind in the reaction liberated hydrohalic acid can be an excess of the reaction Serve amine; but you can also use an organic tertiary base, such as dimethylaniline or pyridine, or inorganic acid-binding substances, such as. B. sodium or potassium carbonate, use.

The N- (haloalkanoyl) -iminodibenzyls required as starting materials are in a known manner by acylation of iminodibenzyl with halogen fatty acid halides or corresponding anhydrides in the presence or absence of z. E.g. pyrzdin, dimethylaniline etc. easily available.

Examples of N - (haloalkanoyl) iminodibenzyls are: Chloroacetyl-, bromoacetyl-, a-chloro-propionyl-, a-bromo-propionyl-, a-bromo-butyryl-, a-bromo-isobutyryl-, ß-chloro-propionyl-, ß-bromopropionyl-, ß-chlorobutyryl-, ß-bromo-butyryl-, ß-chloroisobutyryl, ß-bromo-isobutyryl- and γ-chloro-butyryliminodibenzyl.

These N- (haloalkanoyl) -iminodibenzyls can, for example, with Dimethylamine, methylethylamine, diethylamine, dipropylamine, diisopropylamine, dibutyl and diamylamines, trimethylethylenediamine, triethylethylenediamine, pyrrolidine, piperidine or C-alkylated pyrrolidines or piperidines are implemented.

With inorganic and organic acids, such as. B. hydrochloric acid, sulfuric acid, Phosphoric acid, tartaric acid, citric acid and salicylic acid, form the new compounds Salts that are partially soluble in water with an approximately neutral reaction.

The following examples are intended to explain the preparation of the new compounds in more detail. The parts given are parts by weight. Example i 16 parts of N- (a-bromo-propionyl) -iminodibenzyl ( mp 118 to iig °) are dissolved in 50 parts by volume of absolute benzene, 40 parts by volume of diethylamine are added, after which the mixture is refluxed for 20 hours. After cooling, it is washed thoroughly with water and then the basic components are extracted from the benzene solution using dilute hydrochloric acid. The acidic extracts are made alkaline and the precipitated base is taken up in ether. After drying and evaporation of the ether, the N- (a-diethylamino-propionyl) -iminodibenzyl of F. go ° is obtained with a yield of go ° / o.

In an analogous manner, one obtains using piperidine instead of diethylamine N- (a-piperidino-propionyl) -iminodibenzyl, F. moved to iio °, yield 8ö ° / o.

Example 2 provides, the precipitated base taken up in ether, the ethereal solution dried and the ether evaporated. The N- (Dimethyla, mino-acetyl) -iminodibenzyl is obtained as an oil of bp 176 to 77 ° with a yield of 80%. The hydrochloride melts at 236 to 238 °.

In an analogous reaction with diethylamine, N-diethylarninoacetyl-iminodibenzyl is obtained from b.p. "182 to 183 ° (melting point of the hydrochloride 226 to 228 °) with a yield of 80% and with triethyl-ethylene-diamine the N- (N'-diethylaminoethyl-N'-ethyl-aminoacetyl) -imino-dibenzyl from b.p. 0.2 2o6 to 2o7 ° with a yield of 72%.

Another by reacting N-chloroacetyliminodibenzyl with the corresponding amine produced compound is the N-piperidino-acetyliminodibenzyl, Bp a, 2 = 179 to 180 °, yield 73%.

If N- (a-bromopropionyl) -iminodibenzyl is reacted in an analogous manner with a benzene dimethylamine solution, N- (a-dimethylaminopropionyl) -inninodibenzyl is obtained. Example 3 2 parts of N- (β-bromo-propionyl) -iminodibenzyl (F. iio °) are dissolved in 50 parts by volume of absolute benzene. Then q: 0 parts by volume of about 10% solution of dimethylamine in benzene are added, the batch is initially left to stand for 16 hours at room temperature and then refluxed for a further 2 hours. After cooling, the basic components of the benzene solution are removed with dilute hydrochloric acid, then the hydrochloric acid solution is made alkaline with potassium carbonate and etherified.

After drying and evaporation of the ether, the residue is distilled in a high vacuum. Under 0.2 mm pressure, the N- (β-dimethylaminopropionyl) -iminodibenzyl boils at 95 to ig7 °, yield 50%. Its hydrochloride melts after crystallization from isopropyl alcohol at 168 to 170 °.

In an analogous manner, diethylamine is used instead of dimethylamine the N- (ß-diethylamino-propionyl) -iminodibenzyl, yield 6o%, its hydrochloride melts at 179 to 180 ° (from isopropyl alcohol).

Claims (1)

Claim: Process for the preparation of N-acyl derivatives of iminodibenzyl, characterized in that N- (haloalkanoyl) -iminodibenzyls of the general formula 2 parts of N-chloroacetyl-iminodibenzyl (melting point 92 to g3 °) are dissolved with 6 parts of dimethylamine in 25 parts of benzene, left to stand for 12 hours and then refluxed for another hour. After washing with water, the basic components of the benzol solution are removed with dilute hydrochloric acid. The hydrochloric acid solution becomes alkaline in which n is an integer from r to 3 and Hal is a halogen atom, is reacted in a manner known per se with dialkylamines containing low molecular weight alkyl groups, trialkylalkylenediamines or alkylenimines having 5 to 6 ring members. Attracted publications Journal of Pharmacology and Experimental Therapeutics 47 (r933), p. 69; Journal of the American Chemical Society 52: 2115 (1930); German patent specification 272 529.