DE1265758B - Process for the preparation of o- (beta-dialkylaminoaethoxy) phenyl ketones and their acid addition salts and quaternary salts - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

Int. Cl .:

C07c

German KL: 12 q- 32/20

Number: 1265 758

File number: S 68684IV b / 12 q

Filing date: May 25, 1960

Open date: April 11, 1968

The invention relates to a process for the preparation of ο - (ß - dialkylaminoethoxy) phenyl ketones of the general formula

OR '

wherein R denotes the methyl, the ß-phenylethyl or the a-phenyl-n-propyl radical and R 'den / J-dimethylaminoethyl or denotes the / 5-diethylaminoethyl radical, and their acid addition salts and quaternary salts.

The inventive method is characterized in that one known per se Way corresponding / ί-Dialkylaminoäthylhalogenide or the hydrohalic acid salts thereof are reacted with the corresponding o-hydroxyphenyl ketones and the bases obtained are optionally converted into acid addition salts or quaternary salts.

The reaction is carried out in organic solvents, such as. B. benzene, toluene or xylene made. It can take place in the presence or absence of hydrogen halide acceptors, z. B. anhydrous alkali carbonates or pyridine.

The ethers prepared according to the invention form addition salts with inorganic acids such as hydrochloric acid. These salts can by the action of the acids in suitable solvents, such as Ethyl ether, dissolved bases can be obtained. Forms by reaction with quaternary compounds Agents such as alkyl halides, e.g. As methyl bromide, ethyl iodide and the like, quaternary ammonium compounds can be used produce.

In contrast to the effects to be expected according to the previous knowledge for the new compounds, these show a considerable and very selective coronary vein widening effect in addition to a good anticonvulsant effect. Surprisingly, show the invention. Compounds in which the Öxydiethylaminoalkylkette is arranged in the ortho position to the ketone radical have a significantly greater effect than compounds in which the Alkylkctte. and that. Ketone radicals are in para position. Among the compounds examined, the o »0? -Diethylaminoethoxy) phenylpropiophenone chlorohydrate has proven to be particularly effective. On an isolated mammalian heart according to Langendorff, a method for the production of
o - (/} - dialkylaminoethoxy) phenyl ketones and
their acid addition salts and quaternary salts

Applicant:

P. A. Laboratorio Guidotti & C, Pisa (Italy)

Representative:

Dr.-Ing. E. Hoffmann

and Dipl.-Ing. W. Eitle, patent attorneys,

8000 Munich 8, Maria-Theresia-Str. 6th

Named as inventor:

Gianfranco Di Paco,

Sonnino Celesio Tauro, Pisa (Italy)

this compound at a molar concentration of 2 · 10 ^{-6 was} considered to be less toxic (DL50 taken per os in a rat 156 mg / kg) and did not show any undesirable side effects at the expense of arterial pressure, so that its use in human therapy as a counteracting vein constriction Funds could be recommended.

example 1

500 cm ^{3 of} toluene with 37 g of anhydrous potassium carbonate K2CO3, 0.1 mol of o-hydroxy-3-phenyI-propiophenone and 0.35 mol of β-dimethylaminoethyl chloride were brought to the boil under reflux; the mixture was cooled and filtered, crystallized after distilling off the solvent and the residue was purified after dissolution in ether and reprecipitation by adding petroleum ether; the thus obtained o - (/ S-Dimethylaminoäthoxy) -3-phenyl-propiophenone melts at 50 ⁰ C.

Example 2

0.1 mol of ο-hydroxy-3-phenyl-propiophenone, 0.25 mol of ß-chloroethyl diethylamino-chlorohydrate and 40 g of anhydrous potassium carbonate K2CO3 were refluxed in 500 cm ^{3 of} toluene with stirring until a sample of one toluene solution diluted with ethanol with a drop of ferric chloride solution no longer gave any color reaction.

After cooling, the mixture was filtered, the solvent removed by distillation and the rest fractionated at reduced pressure.

809534/530

IO

15th

20th

The fraction obtained boils at 264 to 268 ° C. at a pressure of 30 mm Hg column and corresponds to the o - (/? - diethylaminoethoxy) -3-phenyl-propiophenone.

Example 3

0.1 mol of o-hydroxy-w-phenyl-w-ethylacetophenone sodium salt and 0.2 mol / I-chloroethyl diethylamine were brought to the boiling point and kept at this temperature for about 2 hours. After adding 250 cm ^{3 of} benzene, the mixture, after it had been left to stand for one night, was filtered, the solvent was removed by distillation and the residue was fractionated under reduced pressure while collecting the product, which was at a temperature of 227 to 229 ⁰ C at 9 mm Hg pressure distilled and the o - (/? - diethylaminoethoxy) -ro-phenyl-w-äthylacetophenon corresponds.

Using the same process, ο- (β-ΌΊ- methylamino-ethoxy) -e> -phenyl - «> - ethylacetophenone was produced at a temperature of 195 to 198 ° C at 10 mm Hg pressure.

Example 4

0.1 mol of ο - (ß - diethylaminoethoxy) - 3r-phenyl - propiophenone were dissolved in 50 cm ^{3 of anhydrous ether and a solution of 50 cm 3 of} ether saturated with hydrogen chloride gas was added.

After cooling and a subsequent rest period, the hydrochloride of o - (/ i-diethylaminoethoxy) -3-phenyl-propiophenone crystallizes in small white needles with a melting point of 128 to 129 ° C from ethanol.

The following additional chlorine hydrates are produced using the same process:

4 a) Chlorohydrate of o - (/ f-DimethyIaminoäthoxy) -3-phenylpropiophenon (Melting point 164 to

165 ° C),
4 b) Hydrochloride of o - (/ i-dimethylaminoethoxy) - «) -phenyl -« - ethylacetophenone (melting point

95 to 98 ⁰ C),
4 c) hydrochloride of o - (/ I-diethylaminoethoxy) -fo-phenyl-w-ethylacetophenone (melting point 88 to 89 ° C).

Heated to reflux. After cooling, the iodine methylate of o - (/? - dimethylaminoethoxy) -r «-phenylco-ethylacetophenone with a melting point of ⁰ ° C. precipitated from ethanol.

The following quaternary salts are also produced using the same process:

5 a) iodine methylate of o- (ß-dimethylaminoethoxy) -

3-phenylpropiophenone (melting point 140 ^f 'C), 5 b) of Jodmethylat o - (/ ^ Dimethylammoäthoxy) -3-phenylpropiophenone (melting point 123 to

125 ° C),
5 c) iodine ethylate of o - (/ i-dimethylaminoethoxy) -

3-phenylpropiophenone (melting point 122 ⁰ C), 5d) Jodmethylat of o - (/ J-Diäthylaminoäthoxy) -fo-phenyl- (u-äthylacetophenon (melting point

65 ° C),
5 e) Iodoethylate of ο - (β - diethylaminoethoxy) -w-phenyl-cu-ethylacetophenone (melting point 91 to 92 ° C).

Claims (1)

Claim: Process for the production of o- (ß-dialkylaminoethoxy) - phenyl ketones of the general formula 40 45 Example 5 0.1 mol of o- (/ i-dimethylaminoethoxy) -f; -phenyl- (o-ethylacetophenone was dissolved in 50 cm ^{3 of} methyl alcohol and 0.3 mol of methyl iodide was added OR ' wherein R denotes the methyl, the / i-phenylethyl or the (x-phenyl-n-propyl radical and R 'den ^ -dimethyl aminoethyl or the / i-diethylaminoethyl radical means, and their acid addition salts and quaternary salts, characterized in that that corresponding / f-dialkylaminoethyl halides are used in a manner known per se or their hydrohalic acid salts with the corresponding o-hydroxyphenyl ketones and the bases obtained are optionally converted into acid addition salts or quaternary salts. Considered publications:
German Patent No. 558,647;
German Auslegeschrift No. 1063 181;
U.S. Patent Nos. 2,668,850, 2,796,435. When the application was announced, a test report with Table I (4 sheets) was displayed.