DE1225646B - Process for the preparation of tertiary amines of the piperidine series - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07d

German class: 12 ρ -1/01

Number: 1225 646

File number: T13911IV d / 12 ρ

Filing date: July 23, 1957

Opening day: September 29, 1966

The invention relates to a process for the preparation of tertiary amines of the piperidine series with the general formula I.

Y V- CH ₂ - CH -;

/ N \ H

wherein R is hydrogen, an alkyl or alkoxy group and Z is a straight or branched chain alkyl or alkenyl radical with 3 or 4 carbon atoms, as well as their acid addition salts, the is characterized in that in a known manner a) Benzylalkyl ketones of the general Formula II

Process for the preparation of tertiary amines
Piperidine series

Applicant:

Dr. Karl Thomae

Company with limited liability,

Biberach / Riss

Named as inventor:

Dipl.-Chem. Dr. Ernst Seeger,

Dipl.-Chem. Dr. August Kottier, Biberach / Riß

CO-Z

II

wherein R and Z have the meaning given above, reductively aminated with piperidine or b) the mentioned ketones with piperidine and formic acid or formates or c) to primary amines of the general formula III

CH ₂ -CH-Z

NH ₂

hydroxide or alkali metal alcoholate reduced at elevated temperature and optionally in the usual way Way, by treating the amines I with acids, the acid addition salts are produced.

The compounds obtainable according to the invention are valuable therapeutics with central stimulants Effect.

III Example 1

l-phenyl-2-piperidino-pentane

wherein R and Z are as defined above, a 1,5-dihalopentane is allowed to act or d) Halogen compounds of the general formula IV

^R ^

Shark

IV

wherein Hal denotes a halogen atom and R and Z are as defined above, with Piperidine converts, or e) α-Piperidinöketone der general formula V

CO-CH-Z V

wherein R and Z have the abovementioned meaning, with hydrazine and the alkali metal alkali to 34 g of piperidine is allowed to drip g anhydrous formic acid or in a flask with a condenser, 18.4 and heated slowly as long in an oil bath to about 170 ⁰ C, until no more distillate passes over. Then allowed to cool, then 16.2 g Benzylpropylketon, 2 g of magnesium chloride hexahydrate and 4.6 g of anhydrous formic acid and heated to 1 ¹ ^ ⁰ hours to 240 C. After cooling,

4c to about 100 ° C., 4.6 g of formic acid again added and again heated to 240 ⁰ C for 1 V ₂ hours. The same operation is repeated two more times. The reaction mixture is then allowed to cool, dilute hydrochloric acid is added until the reaction is acidic, it is extracted with ether, the ether solution is separated off and it is discarded. By adding dilute sodium hydroxide solution to the acidic aqueous solution, the amine is deposited, which is taken up in ether and distilled after the solvent has evaporated. 11 g of l-phenyl-2-piperidino-pentane with a boiling point of 1.595 ° C., the hydrochloride of which melts at 166 to 167 ° C. after recrystallization from acetone, are obtained.

609 668/425

Example 2
1- (p-methylphenyl) -2-piperidino-pentane

Using 17.6 g of p-methylbenzyl propyl ketone 8 g of 1- (p-methylphenyl) -2-piperidinopentane are obtained in the same manner as described above from bp 0.5 116 to 117 ° C. The hydrochloride of the compound melts after recrystallization from acetone at 183 ° C.

Example 3
1-phenyl-2-piperidino-hexane

The procedure described in Example 1 is followed, using 17.6 g of benzyl butyl ketone, and adding after completion However, add 25 ecm of concentrated hydrochloric acid and then heat for another 30 minutes Reflux. The further work-up takes place again as described above. Here are 15 g of amine obtained from bp 0.4 113 ° C, which provide a hydrochloride which, recrystallized from acetone, at 156 to 157 ° C melts.

Example 4
l-phenyl-2-piperidino-pentane

Example 7
1-phenyl-2-piperidino-3-methyl-butane

9.2 g of anhydrous formic acid are added to 17 g of piperidine, which are in a flask with a descending condenser, and the mixture is slowly heated in an oil bath to about 170 ^° C. until no more distillate passes over. After cooling, add 8.2 g Benzylisopropylketon, 1 g of magnesium chloride hexahydrate and 2.3 g of anhydrous formic acid and heated to 240 hours in the oil bath at ⁰ C. then allowed the reaction mixture to cool, are 10 cc of concentrated hydrochloric acid and heated under 20 minutes Reflux. After cooling down, shake it out with ether, separate the ethereal solution and discard it. The base is separated out by adding 10% strength sodium hydroxide solution to the acidic aqueous solution. They are taken up in ether, dried over sodium sulphate, the solvent is evaporated and 3 g of amine are obtained, the colorless crystalline hydrochloride of which melts ^{at 192 ° C. after recrystallization from acetone.}

The acid addition salts with other acids can also be prepared in the usual way. To melt the l-phenyl-2-piperidino-hexane oxalate at 13O ⁰ C and l-phenyl-2-piperidino-pentan-sulfatbei 151 ⁰ C.

2.5 g of 1-phenyl-2-aminopentane and 2.5 g of 1,5-dibromopentane are refluxed with 1 g of sodium acetate in 20 ecm of isopropanol for 3 hours. After the isopropanol has been distilled off, dilute hydrochloric acid is added to the residue until it becomes acidic and then shaken out with ether. The ethereal layer is discarded. The amine is separated from the acidic aqueous solution by adding alkali, which is extracted with ether and then is distilled. Yield 1.5 g. The melting point of the hydrochloride is 167 ^° C.

40

B is ρ ie 1 5
l-phenyl-2-piperidino-pentane

In a shaking autoclave was 16.2 g and 15.0 g Benzylpropylketon piperidine dissolved in 100 cc of anhydrous ethanol, add 0.15 g Platinoxydkatalysator to and passes at a temperature of 125 ⁰ C at a pressure of 100 atmospheres hydrogen so long, until no more recording takes place. The catalyst is then filtered off, the alcohol is evaporated, the residue is taken up in dilute hydrochloric acid and shaken out with ether. The ethereal solution is discarded. The amine is separated from the aqueous acidic solution by adding 10% strength sodium hydroxide solution, taken up in ether and, after the solvent has been driven off, distilled in a fine vacuum. The yield is 4.5 g.

6ö example 6

1-phenyl-2-piperidino-hexane

The procedure is as described in the above example, but using 17.6 g of benzyl butyl ketone and at 200 atmospheric pressure and a temperature of 150 ^° C. This gives 5.0 g of amine.

Claims (1)

Claim: Process for the preparation of tertiary amines of the piperidine series with the general formula I. -CH (S) where R is hydrogen, an alkyl or alkoxy group and Z is a straight or branched chain Means alkyl or alkenyl radical with 3 or 4 carbon atoms, as well as their Acid addition salts, characterized in that, in a manner known per se, a) Benzyl alkyl ketones of the general Formula II -CO wherein R and Z have the meaning given above, reductively aminated with piperidine or b) converts the mentioned ketones with piperidine and formic acid or formates, or c) to primary amines of the general formula III - CH - Z NH ₂ where R and Z have the meaning given above, a 1,5-dihalopentane act or d) halogen compounds of the general formula IV R- CH ₂ - CH - Z IV Shark wherein Hal denotes a halogen atom and R and Z have the meaning given above, with Piperidine converts or e) a-piperidinoketones of the general formula V ^ V - CO - CH - Z V wherein R and Z have the meaning given above, with hydrazine and alkali metal or Reduced alkali hydroxide or alkali alcoholate at elevated temperature and optionally in the usual way Way, by treating the amines I with acids, the acid addition salts are produced. Considered publications:
Announced documents of the Austrian patent specification No. 191 869. When the registration was announced, three pages of the test report were laid out.