DE1194865B - Process for the preparation of 1, 1-diphenyl-3-hexamethylene-iminopropane and its salts - Google Patents

Description

Process for the preparation of 1,1-diphenyl-3-hexamethylene-iminopropane and its salts. It is known that some α, α-diphenyl-γ-dialkylaminobutyramides have a high parasympathicolytic effectiveness. In many cases they are free aminobutyramides more effective; in other cases their quaternary ammonium salts. The most active compound in the group of free aminobutyramides is a, a-diphenyl-y-piperidinobutyramide.

This special effect of the piperidino group was also found in the a, a-diphenyl-l, -piperidinobutyronitrile, the α, α-diphenyl-γ-piperidinopropanol and α, α-diphenyl-γ-piperidinopropane.

It has now been found that 1,1-diphenyl-3-hexamethyleneiminopropane of the formula and its salts are more active than the corresponding piperidino derivative.

It is characterized by an extremely strong parasympathicolytic Effectiveness, especially when administered locally, and exceeds in terms of the effectiveness of all known compounds. The production of 1,1-diphenyl-3-hexamethyleneiminopropane and its salts happen in a manner known per se by either a) 1,1-Diphenyl-3-hexamethyleneiminopropanol- (1) by esterification in the corresponding Hydrohalic acid ester converted and this ester by treatment with hydrogen hydrogenated in the presence of a catalyst or b) 1,1-diphenyl-3-hexamethyleneiminopropanol- (1) reacts simultaneously with hydriodic acid and red phosphorus or c) on a, a-diphenyl-y-hexamethyleneirhinobutyronitrile Sodium amide is allowed to act in excess and the base obtained, if appropriate reacts with acids.

The 1,1-diphenyl-3-hexamethyleneiminopropanol- (1) is preferred reacted with thionyl chloride to give the corresponding hydrochloric acid ester, after which the ester is then catalytically reduced.

The reduction of the hydrogen halide ester is advantageous with gaseous hydrogen and a palladium-containing catalyst carried out.

The following comparison of the 1,1-diphenyl-3-hexamethyleneiminopropane hydrochloride (1) obtained according to the process with the corresponding piperidino derivative (II) shows the superiority of the process product with approximately the same toxicity. Parasympathicolytic toxicity Efficacy (atropine = 1) Analgesic LD5 ° Mydriasi; Efficacy intravenously intra- (morphine = 1) in the rat Local peritoneal ileum (mg / kg) I 0.05 0.1 0.08 0 25 1I 0.05 0.02 0.01 0 24 In addition to its parasympathicolytic activity, 1,1-diphenyl-3-hexamethyleneiminopropane has a pronounced inhibitory effect on the central nervous system in such a way that the tendency towards aggressiveness is dampened; the well-known piperidino derivative does not have this property.

The following examples illustrate preferred embodiments of the claimed process. EXAMPLE 1 A suspension of 0.2 to 1 mol of sodium amide in 200 cm 3 of xylene, in which 0.1 mol of α, α-diphenylyhexamethyleneiminobutyronitrile is dissolved, is heated to the boil for 12 hours. The excess sodium amide is then decomposed with water; the xylene layer is separated, washed with water and extracted with hydrochloric acid. This acidic extract is made strongly alkaline with concentrated lye; the deposited base is extracted with ether. After drying, the ether is evaporated off and the 1,1-diphenyl-3-hexamethyleneiminopropane is distilled in vacuo. Bp 170 to 174 ° C; Refractive index nö = 1.5636; Density d. "= 1.009. The yield is 75 () / o.

Acid addition salts can be obtained from the oil obtained by reacting with Acids containing non-toxic anions are obtained. The hydrochloric acid Salt melts at 189 to 192 ° C.

Example 2 Dissolved in 31 g of 1,1-diphenyl-3-hexamethyleneiminopropanol- (1) in chloroform, an excess of thionyl chloride is added; the mixture becomes heated under reflux for 3 hours. The reaction mixture is then reduced under reduced Pressure evaporated to dryness; the residue is by dissolving in warm ethanol and Dilute this solution with ethyl acetate recrystallized.

The resulting aqueous solution of 1,1-diphenyl-1-chloro-3-hexamethyleneiminopropane - Hydrochloride is combined with gaseous hydrogen in the presence of a buffered palladium-carbon catalyst hydrogenated at a pressure of 3 atmospheres. The 1.1 -diphenyl-3-hexamethyleneiminopropane obtained is purified by distillation under reduced pressure. Kp.i 170 to 174'C. The yield is 68%.

Example 3 A mixture of 0.7 mol of 1,1-diphenyl-3-hexamethyleneiminopropanol- (1), 0.9 mol of red phosphorus and 1.15 mol of 47% strength hydriodic acid in 550 cm3 of glacial acetic acid is refluxed for 3 hours. After the reaction has ended, the warm solution is filtered through a glass filter. diluted with 1500 cm3 of water and cooled. The 1,1-diphenyl-3-hexamethyleneiminopropane hydroiodide which precipitates out is filtered off, washed with cold water and then resuspended in water; the base is liberated by adding sodium hydroxide until it is strongly alkaline. The base is extracted with ether, the ethereal solution is dried over potassium carbonate and the ether is evaporated. The reaction product obtained is treated further under the conditions of Example 2 and proves to be identical to the process product of this example. The yield is 550.0.

The a, a-diphenyl -, - hexamethyleneiminobutyronitrile used as starting material according to Example 1 is in a manner known per se by reacting diphenylacetonitrile with hexamethyleneiminoethyl chloride or by reacting hexamethylene imine with a, a-diphenyl - "- bromobutyronitrile. The l, l-diphenyl-3-hexamethyleneiminopropanol (1) used as starting material according to Examples 2 and 3 is in a manner known per se by reacting a phenylmagnesium halide with ß-Hexamethyleneiminopropionic acid ethyl ester produced.

Claims (2)

Claims: 1. Process for the preparation of 1,1-diphenyl-3-hexamethyleneiminopropane of the formula and its salts. characterized in that either a) 1.1 - Diphenyl - 3 - hexamethyleneiminopropanol- (1) is converted into the corresponding hydrohalic acid ester by esterification and this ester is hydrogenated by treatment with hydrogen in the presence of a catalyst, or b) 1.1 - Diphenyl-3-hexamethyleneiminopropanol- (1) is reacted simultaneously with hydriodic acid and red phosphorus or c) an excess of aa-diphenyl-y-hexamethyleneiminobutyronitrile is allowed to act on sodium amide and the base obtained is optionally reacted with acids. 2. The method according to claim 1, characterized in that one the 1.l-diphenyl-3-hexamethyleneiminopropanol- (1) by treatment with thionyl chloride esterified.