CH394246A - Process for the preparation of 1-phenyl-1-O-chlorophenyl-3-dimethyl-aminopropanol- (1) - Google Patents
Process for the preparation of 1-phenyl-1-O-chlorophenyl-3-dimethyl-aminopropanol- (1)Info
- Publication number
- CH394246A CH394246A CH1039263A CH1039263A CH394246A CH 394246 A CH394246 A CH 394246A CH 1039263 A CH1039263 A CH 1039263A CH 1039263 A CH1039263 A CH 1039263A CH 394246 A CH394246 A CH 394246A
- Authority
- CH
- Switzerland
- Prior art keywords
- chlorophenyl
- phenyl
- dimethyl
- preparation
- aminopropanol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 8
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 5
- VMHYWKBKHMYRNF-UHFFFAOYSA-N (2-chlorophenyl)-phenylmethanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CC=C1 VMHYWKBKHMYRNF-UHFFFAOYSA-N 0.000 claims description 4
- PIDPNJFONDWEQH-UHFFFAOYSA-N CN(C(CC(O)(C1=C(C=CC=C1)Cl)C1=CC=CC=C1)=O)C Chemical compound CN(C(CC(O)(C1=C(C=CC=C1)Cl)C1=CC=CC=C1)=O)C PIDPNJFONDWEQH-UHFFFAOYSA-N 0.000 claims description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
- KKPMIUJEKFOUFK-UHFFFAOYSA-N ethyl 3-(2-chlorophenyl)-3-hydroxy-3-phenylpropanoate Chemical compound CCOC(=O)CC(O)(c1ccccc1)c1ccccc1Cl KKPMIUJEKFOUFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 4
- 239000011701 zinc Substances 0.000 claims description 4
- 229910052725 zinc Inorganic materials 0.000 claims description 4
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- MCNQZCHJBLFDHK-UHFFFAOYSA-N 1-(2-chlorophenyl)-2-(dimethylamino)propan-1-one Chemical compound CN(C)C(C(=O)C1=C(C=CC=C1)Cl)C MCNQZCHJBLFDHK-UHFFFAOYSA-N 0.000 description 1
- PQWGFUFROKIJBO-UHFFFAOYSA-N 1-(3-chlorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC=CC(Cl)=C1 PQWGFUFROKIJBO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- YKJZHCGKDFIXBP-UHFFFAOYSA-N C1(=CC=CC=C1)C(C(C(=O)N(C)C)O)C1=C(C=CC=C1)Cl Chemical compound C1(=CC=CC=C1)C(C(C(=O)N(C)C)O)C1=C(C=CC=C1)Cl YKJZHCGKDFIXBP-UHFFFAOYSA-N 0.000 description 1
- OLDTXMFXKJQWCH-UHFFFAOYSA-N C1(=CC=CC=C1)C(CC(=O)O)(O)C1=C(C=CC=C1)Cl Chemical compound C1(=CC=CC=C1)C(CC(=O)O)(O)C1=C(C=CC=C1)Cl OLDTXMFXKJQWCH-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- BQRIIWKHNJGQFH-UHFFFAOYSA-M [Br-].[Mg+]C1=CC=CC=C1Cl Chemical compound [Br-].[Mg+]C1=CC=CC=C1Cl BQRIIWKHNJGQFH-UHFFFAOYSA-M 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
- 229940072033 potash Drugs 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000006485 reductive methylation reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von l-Phenyl-l-o-chlorphenyl-3-dimethyl-aminopropanol-(1)
Es ist bekannt, dass l-Phenyl-l-o-chlorphenyl-3- dimethylamino-propanol-(l) durch Kondensation von o-Chlorbenzophenon mit Essigsäurenitril und nachfolgende reduktive Methylierung zubereitet werden kann (DBP 1051281). Dieselbe Verbindung wird auch durch Einwirkung eines Gemisches der Grignard-Verbindungen aus Brombenzol und o-Chlorbenzol erhalten, sowie durch Einwirkung von Phenylmagnesiumbromid auf Dimethylamino-o-chlorpropiophenon, bzw. durch die Reaktion von o-Chlorphenylmagnesiumbromid mit Chlorpropiophenon und nachfolgende Bearbeitung mit Dimethylamin (DBP 1080568, DBP 1083277, Jug. Pat. 22729, Croat.
Chem. Acta 32 [1960] 209).
Erfindungsgemäss wird nun so vorgegangen, dass o-Chlorbenzophenon mit Bromessigsäureäthylester in Gegenwart von Zink zu 3-Phenyl-3-o-chlorphenyl 3-hydroxypropionsäure-äthylester umgesetzt wird, dieser mit Dimethylamin zu N,N-Dimethyl-3-phenyl- 3 -o-chlorphenyl-3 -hydroxypropionsäureamid umgesetzt und mit Lithiumaluminiumhydrid zu l-Phenyl l-o-chlorphenyl-3-dimethylaminopropanol-(1) reduziert wird. Die Hydrolyse von N,N-Dimethyl-3-phe- nyl-3-o-chlorphenyl-3-hydroxypropionamid ergibt 3 Phenyl-3-o-chlorphenyl-3-hydroxypropionsäure.
Beispiel
Eine Mischung von 0,12 Grammatom Zink, 20 ccm trockenem Benzol und einer Spur Jod wird unter Rühren zur Siedetemperatur erhitzt. Alsdann wird eine Lösung von 0,1 Mol o-Chlorbenzophenon und 0,12 Mol Bromessigsäure-äthylester derart zugetropft, dass die Reaktionsmischung im Sieden erhalten wird. Nach Beendigung des Zutropfens wurde das Gemisch noch eine Stunde im Sieden gehalten, wobei der grösste Teil vom Zink gelöst wird. Nach Abkühlen wurde die Mischung mit einem Überschuss an verdünnter Schwefelsäure versetzt, die Benzolschicht abgetrennt, mit verdünnter Schwefelsäure gewaschen und mit Magnesiumsulfat getrocknet.
Nachdem das Benzol durch Verdampfen entfernt wurde, hinterbleibt der rohe 3-Phenyl-3-o-chlorphenyl-3-hydroxypropionsäure-äthylester als gelbes Ö1.
Ein Muster wurde zur Analyse bei 0,08 mm Hg und 1200C (Temperatur im Block gemessen) destilliert.
Der rohe 3-Phenyl-3-o-chlorphenyl-3 -hydroxypropionsäure-äthylester (0,1 Mol) wurde in 20 ccm Athanol gelöst und ein Überschuss an Dimethylamin in alkoholischer Lösung zugegeben. Die Reaktionslösung wurde einige Tage bei Zimmertemperatur stehengelassen und durch Destillation von Äthanol befreit. Es hinterbleibt ein rohes öl, das in Benzol gelöst und mit verdünnter Salzsäure und Wasser gewaschen wurde. Nach Trocknen mit Magnesiumsulfat wurde das Benzol abgedampft und das rohe hinterbliebene N,N-dimethyl-3 -phenyl-3 -o-chlorphe- nyl-hydroxypropionsäureamid zur Analyse bei 0,08 mm Hg und llO"C (Temperatur im Block gemessen) destilliert.
Zu einer Suspension von 0,25 Mol feingepulvertem Lithiumaluminiumhydrid in 50 ccm trockenem Ather wurde eine Lösung von 0,1 Mol rohem N,N- dimethyl-3 -phenyl-3-o- chlorphenyl-3 -hydroxypro- pionsäureamid in 50 ccm trockenem Äther unter Rühren vorsichtig zugetropft. Nach Beendigung der Zugabe wurde die Suspension unter Rühren und Rück flusskühlung noch vier Stunden gekocht, und alsdann 50 ccm Wasser zur Zersetzung des Überschusses von Lithiumaluminiumhydrid zugegeben. Die entstandene Suspension wurde mit 150 ccm 10 0/einer Natronlauge versetzt, die ätherische Schicht abgetrennt und die wässrige Schicht mit frischem Äther ausgeschüttelt.
Die vereinigten Ätherauszüge wurden mit Pottasche getrocknet und durch Verdampfen von Äther befreit.
Es blieb ein helles öl zurück, das nach einigem Stehen teilweise kristallisierte. Das rohe Produkt wurde durch Umlösung aus Essigester-Petroläther gereinigt, wobei weisses, kristallinisches l-Phenyl-l o-chlorphenyl-3-dimethylaminopropanol-(1) vom F.
123"C erhalten wurde. Das Hydrochlorid schmilzt bei 1910C.
Process for the preparation of l-phenyl-l-o-chlorophenyl-3-dimethyl-aminopropanol- (1)
It is known that l-phenyl-l-o-chlorophenyl-3-dimethylamino-propanol- (l) can be prepared by condensation of o-chlorobenzophenone with acetic acid nitrile and subsequent reductive methylation (DBP 1051281). The same compound is also obtained by the action of a mixture of the Grignard compounds from bromobenzene and o-chlorobenzene, as well as by the action of phenylmagnesium bromide on dimethylamino-o-chloropropiophenone, or by the reaction of o-chlorophenylmagnesium bromide with chloropropiophenone and subsequent processing with dimethylamine (DBP 1080568, DBP 1083277, Jug. Pat. 22729, Croat.
Chem. Acta 32 [1960] 209).
According to the invention, the procedure is that o-chlorobenzophenone is reacted with ethyl bromoacetate in the presence of zinc to give 3-phenyl-3-o-chlorophenyl 3-hydroxypropionic acid ethyl ester, this with dimethylamine to give N, N-dimethyl-3-phenyl-3 - o-chlorophenyl-3-hydroxypropionic acid amide reacted and reduced with lithium aluminum hydride to l-phenyl lo-chlorophenyl-3-dimethylaminopropanol- (1). The hydrolysis of N, N-dimethyl-3-phenyl-3-o-chlorophenyl-3-hydroxypropionamide gives 3-phenyl-3-o-chlorophenyl-3-hydroxypropionic acid.
example
A mixture of 0.12 gram atom of zinc, 20 cc of dry benzene and a trace of iodine is heated to the boiling point with stirring. A solution of 0.1 mol of o-chlorobenzophenone and 0.12 mol of ethyl bromoacetate is then added dropwise in such a way that the reaction mixture is obtained at the boil. After the end of the dropwise addition, the mixture was kept at the boil for a further hour, most of the zinc being dissolved. After cooling, an excess of dilute sulfuric acid was added to the mixture, the benzene layer was separated off, washed with dilute sulfuric acid and dried with magnesium sulfate.
After the benzene has been removed by evaporation, the crude ethyl 3-phenyl-3-o-chlorophenyl-3-hydroxypropionate remains as a yellow oil.
A sample was distilled for analysis at 0.08 mm Hg and 1200 ° C. (temperature measured in the block).
The crude 3-phenyl-3-o-chlorophenyl-3-hydroxypropionic acid ethyl ester (0.1 mol) was dissolved in 20 cc of ethanol and an excess of dimethylamine in alcoholic solution was added. The reaction solution was left to stand for a few days at room temperature and freed from ethanol by distillation. A crude oil remains, which was dissolved in benzene and washed with dilute hydrochloric acid and water. After drying with magnesium sulfate, the benzene was evaporated and the crude remaining N, N-dimethyl-3-phenyl-3 -o-chlorophenyl-hydroxypropionic acid amide was distilled for analysis at 0.08 mm Hg and 110 ° C. (temperature measured in the block) .
A solution of 0.1 mol of crude N, N-dimethyl-3-phenyl-3-o-chlorophenyl-3-hydroxypropionic acid amide in 50 cc of dry ether was added to a suspension of 0.25 mol of finely powdered lithium aluminum hydride in 50 cc of dry ether Carefully added dropwise with stirring. After the addition was complete, the suspension was boiled for a further four hours with stirring and reflux cooling, and then 50 ccm of water was added to decompose the excess lithium aluminum hydride. The resulting suspension was mixed with 150 ccm 10 0 / a sodium hydroxide solution, the ethereal layer was separated and the aqueous layer was shaken out with fresh ether.
The combined ether extracts were dried with potash and freed from ether by evaporation.
A pale oil remained, which partially crystallized after standing for a while. The crude product was purified by dissolving from ethyl acetate-petroleum ether, whereby white, crystalline l-phenyl-l o-chlorophenyl-3-dimethylaminopropanol- (1) from F.
123 "C. The hydrochloride melts at 1910C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU160162 | 1962-12-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH394246A true CH394246A (en) | 1965-06-30 |
Family
ID=25554831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1039263A CH394246A (en) | 1962-12-09 | 1963-08-22 | Process for the preparation of 1-phenyl-1-O-chlorophenyl-3-dimethyl-aminopropanol- (1) |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH394246A (en) |
-
1963
- 1963-08-22 CH CH1039263A patent/CH394246A/en unknown
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