DE1906551B2 - 2-alkoxy-3,5-dihalophenyl dialkylaminoalkyl ethers - Google Patents

Description

R ² ίο add 2 liters of water, continually

OR ³ stirs. The chlorinated compound crystallizes out. she

_J IL γ ™ * ^ά suctioned off, washed and with 125 ml 30% iger

- "\ / ~ Sodium hydroxide solution deacetylated. The product is distilled

and then recrystallized from petroleum ether. In the η and m 0, 1 or 2, 15 66 g of 3,5-dichloroguajakol (melting point 62 to 63 ° C, ex

R ¹ , R * and R ^a the methyl, ethyl or propyl booty 68%).

r ^ a ^ au »or the M ^ l-, ** ■ ** ^B:

or propyl group as well

X and Y mean fluorine, chlorine or bromine atoms, *> 50 g of 3,5-dichloroguajakol (0.25 mol) are poured into a

and their salts with inorganic or organic sodium ethylate solution, which are made from 6 g of sodium

niche acids. and 68 ml of absolute alcohol is made

2. Process for the preparation of the 2-alkoxy A red solution is obtained which contains 39 g (0.26 mol 3,5 - dihalogenphenyldialkylaminoalkyl ether after + 10% excess) diethylaminoethyl chloride added claim 1, characterized in that "5" is added.

In each case, in a manner known per se, a Brenz-Man is carefully warmed up; the solution becomes cloudy and

catechol monoalkyl ethers acetylated and halogenated. Sodium chloride precipitates. The mixture is then heated for 7 hours

the compound thus obtained is deacetylated and refluxed with long. Then you cool and

300 ml of water and 25 ml of concentrated hydrochloric acid are added to a corresponding alkylaminoalkyl chloride and if necessary add the resulting ether 30. The aqueous solution is filtered and poured over

transferred into the sake with acids. Activated carbon passed. The base is mixed with 40 ml of am-

3. Medicinal products containing the 2-alkoxy-3,5-di- monia precipitated and extracted with ether. To Halophenyldialkylaminoalkyl ether after distillation of the ether gives 51 g (yield Proverb 1 as an active ingredient. 72%) l-diethylaminoethoxy-2-methoxy-3,5-dichloro

35 benzene (bp. 7165-166 ⁰ C).

Stage C: L-diethylaminoethoxy hydrochloride

2-methoxy-3,5-dichlorobenzene

The invention relates to the one achieved in the claims in the preceding method step

marked object. 40 base obtained in 100 ml of acetone and adds a solution

The compounds of the invention have valuable solution of 6.35 g of dry hydrochloric acid in 20 ml of acetone pharmacological properties, especially as an additive. The hydrochloride of 1-diethylaminoethoxy-spasmogenic. In animal experiments, their excess 2-methoxy-3,5-dichlorobenzene precipitates, is removed from the comparison compound acetyl suction, washed with acetone and then dried, choline can be shown (see test reports). 45 is obtained 51 g of product (mp. 132 to 134 ⁰ C).

The compounds of the invention can be prepared

by using an ^{ana |} y ^se

A catechol monoalkyl ether is acetylated. Calculated%: C 47.49, H 6.09, Cl 32.42, N 4.26;

and halogenated, the compound thus obtained was found%: C 47.31. H 6.14, Cl 32.24, N 4.18.
acetylated and with a corresponding alkylamino 50

reacts alkyl chloride and, if necessary, the formed Example 2

deten ether converted into salts with acids. 1-dimethylaminopropoxy hydrochloride

The preparation of some compounds according to the invention 2-methoxy-3,5-dichlorobenzene
fertilize is used in the following examples

explained in more detail. 55 Stage A is described as in Example 1

Example 1 carried out.

_TT ,,, .. ,, _. ",, ..,", Level B: l-dimethylaminopropoxy-2-methoxy-

1-Diethylammoathoxy-2-methoxy-3 5-dichlorobenzene hydrochloride

3,5-dichlorobenzene

".., ._.... ,, 60 63 g of 3,5-dichloroguajakol (0.32 mol) are added to

Stage A: 3,5-Dichlorguajakol _a sodium ethylate solution, which is made from 7.5g Na-

In a 250 ml flask with a reflux condenser, ace- trium and 100 ml ethyl alcohol are obtained. 44 g are added 62 g of guaiacol (0.5 mol) are tylated with acetic acid (0.326 mol + 10% excess) 1-dimethylamino * anhydride is added in the presence of a few drops of concentrated 3-chloropropane and the resulting sulfuric acid is heated. When the reaction is complete, mix at reflux for 6 hours. One observes the sulfuric acid is neutralized with sodium acetate. a precipitation of sodium chloride. One cools and After cooling the solution, the chlorination of the extracted with 300 ml of water and concentrated 30 ml follows Guaiacol acetate. Hydrochloric acid. The aqueous solution is poured over activated charcoal

3 4

directed. The base obtained is added by adding anhydrous hydrochloric acid to the same

Ammonia precipitated Extract with ether, bubble in a quantity of acetone and add this solution

evaporate this and distill the residue. Base until the color changes from methyl red Das

63 g (yield 70%) of 1-dimethylamino hydrochloride are obtained which crystallize out. It is sucked off,

propoxy ^ -methoxyO.S-dichlorobenzene (bp 25 190 to 5 wash and then in the air and in the heat

195 ° Q. cabinet dried at 30 ⁰ C. It gets out several times

_c . , ρ "j., ... , _ ,. . ,. Isopropanol recrystallized. 51 g of 1-di-

Level C: Hydrochlond d «i 1-Duneüiylainmo- äthVlaEopropox _y -2- _m ethox _y -3,5. <Üchlorbenio! -Hy-

propoxy ^ -methoxy-S.S-dichlorobenzene hydrochloride (melting point 142 ° C; yield 48%).

The io obtained in the previous step Base is dissolved in 180 ml of acetone. Analysis is added

7.85 g of anhydrous hydrochloric acid in 70 ml of acetone Calculated%: C 49.05, H 6.42, Cl 31.09, N 4.09;

is resolved. The 1-diaethyl hydrochloride found%: C 49.16, H 6.46, Cl 30.90, N 4.19. ammopropoxy-2-medu} xy-3,5-dichlorobeazols precipitates.

It is a colorless solid (mp. 138 to 140 ⁰ C). 15 B is ρ ie 1 4

1-diethylaminoisopropoxy ^ -methoxy-S.S-dichloro-Calculated%: C 45.79, H 5.72, Cl 33.86, N 4.45; benzene oxalate

Found%: C 45.59, H 5.79, α 3j, 72, N 4.39. _. _o,. . . W _D , 1 uu 1,

Stage A is described as in Example 1

Example 3 30 carried out Hydrochloride of 1-diethyiaminopropoxy stage B: l-diethyIaminoisopropioxy-2-methoxy-

2-methoxy-3,5-dichlorobenzene 3,5-dichlorobenzene

The mare Λ is described in Example 1, 63 g of 3,5-dichloroguajakol (0.326 mol) become

carried out 95 sodium ethylate added, which by dissolving

". _, _._ ... -, is obtained from 7.5 g of sodium in 100 ml of alcohol.

Step B: l-Diathylaminopropoxy-2-methoxy- _the resulting solution added to 54 g (0.326 mol

3,5-dichlorobenzene + 10% excess) jJ-chloropropyl diethylamine added.

The 66 g obtained in the previous stage. The mixture is heated for 7 hours, Na-

3,5-DichlorguajakoI (0.34 mol) will precipitate into sodium chloride. Extract with 300 ml

itriumäthylatlösung given, which nitrated from 7 g of sodium and water and 4.5 ml of concentrated hydrochloric acid

130 ml of absolute alcohol is produced. The solution is added to this and 60 ml of ammonia are added. From-

Holding the red solution, 55 g of diethylamino-precipitated base are added and the mixture is extracted with ether. One steams

propyl chloride (0.34 mol + 10% excess) was added. the ether off and the residue is distilled.

One warms carefully. After 5 minutes cloudy 35 70 g (yield 7-10%) of 1-diethyl

the solution and sodium chloride precipitate. One aminoisopropoxy-3,5-dichlorobenzene (b.p. 5 166 bis

then refluxed for 2 hours. 167 ° C).

Cool and add water. The amine falls c. »Ο 1 t

the end. Do you decant? extracted several times with Me- ^{level C:} l-

ethylene chloride and washes the organic solution with 40

a 4% sodium hydroxide solution and with The base obtained above is removed in 130 ml

Water. It is dried over potassium carbonate and dissolved alcohol. Add a solution of

removes the solvent. 96 g of 1-di- 21 g of oxalic acid in 40 ml of alcohol are obtained. The oxalate

äthylaminopropoxy ^ -methoxy-S.S-dichlorobenzoliAus- des l-diethylaminoisopropoxy ^ -methoxy-S.S-dichloro-

prey: 95%). 45 benzene precipitates, is sucked off, mixed with alcohol

o t π τ »j Li -λ j 1 η- L 1 · wash and dry (melting point 128 ° C.).

Stage C: Hydrochloride of 1-diethylaminopropoxy-

2-methoxy-3,5-dichlorobenzene analysis

The base obtained in the previous step Calculated%: C 48.48, H 5.81, Cl 17.93, N 3.53;

is dissolved in twice the amount by weight of acetone. 50 found%: C 48.28, H 5.98, Cl 17.80, N 3.39.

Claims (1)

L J IL The patent claims obtained in the previous step: The solution is placed in a 1-1 round bottom flask equipped with a stirrer and thermometer and added 1. Add 2-alkoxy-3,5-dihalogenphenyl-dialkylamino-150 ml acetic acid. One then gives in small alkyl ethers of the general formula 5 Meugen gradually add 160 g of chlorosuccinimide. The suspension is then heated to 50 to 55 ° C and ι Ri then keeps them in the warming cabinet for 117 hours / 55 ° C. -N. _Na g _{n Abscn} IUSS the reaction mixture is cooled and