AT242120B - Process for the preparation of 1-phenyl-1- (o-chlorophenyl) -3-dimethylaminopropanol- (1) - Google Patents
Process for the preparation of 1-phenyl-1- (o-chlorophenyl) -3-dimethylaminopropanol- (1)Info
- Publication number
- AT242120B AT242120B AT867963A AT867963A AT242120B AT 242120 B AT242120 B AT 242120B AT 867963 A AT867963 A AT 867963A AT 867963 A AT867963 A AT 867963A AT 242120 B AT242120 B AT 242120B
- Authority
- AT
- Austria
- Prior art keywords
- chlorophenyl
- phenyl
- dimethylaminopropanol
- preparation
- ether
- Prior art date
Links
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- VMHYWKBKHMYRNF-UHFFFAOYSA-N (2-chlorophenyl)-phenylmethanone Chemical compound ClC1=CC=CC=C1C(=O)C1=CC=CC=C1 VMHYWKBKHMYRNF-UHFFFAOYSA-N 0.000 claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 3
- 239000011701 zinc Substances 0.000 claims description 3
- 229910052725 zinc Inorganic materials 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- -1 acetic acid nitrile Chemical class 0.000 description 5
- 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 description 4
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KKPMIUJEKFOUFK-UHFFFAOYSA-N ethyl 3-(2-chlorophenyl)-3-hydroxy-3-phenylpropanoate Chemical compound CCOC(=O)CC(O)(c1ccccc1)c1ccccc1Cl KKPMIUJEKFOUFK-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 238000009835 boiling Methods 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
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- KTJRGPZVSKWRTJ-UHFFFAOYSA-N 3-chloro-1-phenylpropan-1-one Chemical compound ClCCC(=O)C1=CC=CC=C1 KTJRGPZVSKWRTJ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-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
- 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
- 238000001816 cooling Methods 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
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 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
- 230000020477 pH reduction Effects 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
- 230000002829 reductive effect Effects 0.000 description 1
- 238000006485 reductive methylation reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
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Verfahren zur Herstellung von l-Phenyl-l- (o-chlorphenyl)-3-dimethylaminopropanol- (1)
Es ist bekannt, dass 1-Phenyl-1- (0-chlorphenyl) -3-dimethylaminpropanol- (1) durch Kondensation von o-Chlorbenzophenon mit Essigsäurenitril und nachfolgende reduktive Methylierung hergestellt werden kann (deutsche Patentschrift Nr. 1051281).
Dieselbe Verbindung wird auch durch Einwirkung eines Gemisches der Grignard-Verbindungen aus Brombenzol und o-Chlorbenzol auf ss-Dimethylaminopropionsäure- äthylester erhalten, sowie durch Einwirkung von Phenylmagnesiumbromid auf w-Dimethylamino-o-chlor- propiophenon bzw. durch die Reaktion von o-Chlorphenylmagnesiumbromid mit ss-Chlorpropiophenon und nachfolgende Bearbeitung mit Dimethylamin (deutsche Patentschriften Nr. 1080568 und Nr. 1083277, jugoslawische Patentschrift Nr. 22729, croat. Chem.
Acta 32 [1960] 209).
EMI1.1
(o-chlorphenyl)-3-hydroxypropionsäureäthylesterBearbeitung mit Dimethylamin zu N, N-Dimethyl-3-phenyl-3- (o-chlorphenyl)-3-hydroxypropionsäure- amid umgesetzt wird, welches mit Lithiumaluminiumhydrid zu 1-Phenyl-1- (0-chlorphenyl) -3-dimethyl- aminopropanol- (l) reduziert wird. Die Hydrolyse von 3-Phenyl-3- (o-chlorphenyl)-3-hydroxypropionsäureäthylester odervon N, N-Dimethyl-3-phenyl-3- (o-chlorphenyl)-3-hydroxypropionamid ergibt 3-Phenyl-3- (o-chlorphenyl)-3-hydroxypropionsäure.
Das Verfahren wird durch folgendes Beispiel illustriert :
Beispiel : Eine Mischung von 0, 12 Gramatomen Zink, 20 cm3 trockenem Benzol und einer Spur Jod wurde unter Rühren zur Siedetemperatur erhitzt. Sodann wurde eine Lösung von 0, 1 Mol o-Chlorbenzophenon und 0, 12 Mol Bromessigsäureäthylester derart zugetropft, dass die Reaktionsmischung im Sieden gehalten wurde. Nach Beendigung des Zutropfens wurde das Gemisch noch 1 h sieden gelassen, wobei der grösste Teil vom Zink gelöst wurde. Nach Abkühlung 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 worden war, blieb der rohe 3-Phenyl-3-(o-chlorphenyl)-3-hydroxypropionsäureäthylester als gelbes Öl zurück.
Eine Probe wurde zur Analyse bei 0, 08 mm Hg und 1200C (Temperatur im Block gemessen) destilliert.
Der rohe 3-Phenyl-3-(o-chlorphenyl)-3-hydroxypropionsäureäthylester (0,1 Mol) wurde in 2u cm' Äthanol gelöst, und ein Überschuss an Dimethylamin in alkoholischer Lösung wurde zugegeben. Die Reaktionslösung wurde einige Tage bei Zimmertemperatur stehengelassen und durch Destillation von Äthanol befreit. Es blieb ein rohes Öl zurück, das in Benzol gelöst und mit verdünnter Salzsäure und Wasser gewaschen wurde. Nach Trocknen mit Magnesiumsulfat wurde das Benzol abgedampft und das so erhaltene rohe N, N-Dimethyl-3-phenyl-3- (o-chlorphenyl)-3-hydroxypropionsäureamid zur Analyse bei 0, 08 mm Hg und 1100C (Temperatur im Block gemessen) destilliert.
Zu einer Suspension von 0, 25 Mol feingepulvertem Lithiumaluminiumhydrid in 50 cms trockenem Äther wurde eine Lösung von 0, 1 Mol rohem N, N-Dimethyl-3-phenyl-3- (o-chlorphenyl)-3-hydroxypropionsäureamid in 50 cms trockenem Äther unter Rühren vorsichtig zugetropft. Nach Beendigung der Zugabe wurde die Suspension unter Rühren und Rückflusskühlung noch 4 h gekocht, wonach 50 cm'Wasser zur Zersetzung des Überschusses von Lithiumaluminiumhydrid zugegeben wurden. Die entstandene Suspension wurde mit 150 cms ioloiger Natronlauge versetzt, die ätherische Schichte abgetrennt und die
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wässerige Schichte 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 1-Phenyl-1- (o-chlorphenyl)-3-dimethylaminopropanol- (1), F = 123 C, erhalten wurde. Das Hydrochlorid wurde mittels alkoholischer Chlorwasserstofflösung erhalten und aus Äthanol-Äther umkristallisiert ; F = 191 C.
EMI2.1
lösung durch Verdampfen von Methanol befreit, mit Wasser versetzt und mit Äther ausgeschüttelt. Die wässerige Schicht ergab nach Ansäuern mit Salzsäure die rohe 3-Phenyl-3- (o-chlorphenyl)-3-hydroxy- propionsäure, die aus Benzol-Petroläther umkristallisiert wurde ; F = 1550C.
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Process for the preparation of l-phenyl-l- (o-chlorophenyl) -3-dimethylaminopropanol- (1)
It is known that 1-phenyl-1- (0-chlorophenyl) -3-dimethylaminopropanol- (1) can be prepared by condensation of o-chlorobenzophenone with acetic acid nitrile and subsequent reductive methylation (German patent specification No. 1051281).
The same compound is also obtained by the action of a mixture of the Grignard compounds of bromobenzene and o-chlorobenzene on s-dimethylaminopropionic acid ethyl ester, as well as by the action of phenylmagnesium bromide on w-dimethylamino-o-chloropropiophenone or by the reaction of o-chlorophenylmagnesium bromide with ss-chloropropiophenone and subsequent processing with dimethylamine (German patents No. 1080568 and No. 1083277, Yugoslav patent No. 22729, Croat. Chem.
Acta 32 [1960] 209).
EMI1.1
Ethyl (o-chlorophenyl) -3-hydroxypropionate processing with dimethylamine to give N, N-dimethyl-3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionic acid amide, which is converted with lithium aluminum hydride to 1-phenyl-1- (0 -chlorphenyl) -3-dimethyl-aminopropanol- (l) is reduced. The hydrolysis of 3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionic acid ethyl ester or of N, N-dimethyl-3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionamide gives 3-phenyl-3- (o- chlorophenyl) -3-hydroxypropionic acid.
The procedure is illustrated by the following example:
Example: A mixture of 0.12 gramatoms of zinc, 20 cm3 of dry benzene and a trace of iodine was heated to boiling temperature while stirring. A solution of 0.1 mol of o-chlorobenzophenone and 0.12 mol of ethyl bromoacetate was then added dropwise in such a way that the reaction mixture was kept boiling. After the end of the dropping, the mixture was left to boil for a further 1 hour, most of the zinc being dissolved. After cooling, the mixture was treated with an excess of dilute sulfuric acid, the benzene layer was separated off, washed with dilute sulfuric acid and dried with magnesium sulfate. After the benzene had been removed by evaporation, the crude ethyl 3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionate remained as a yellow oil.
A sample was distilled for analysis at 0.08 mm Hg and 1200C (temperature measured in the block).
The crude ethyl 3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionate (0.1 mol) was dissolved in 2u cm '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 remained, which was dissolved in benzene and washed with dilute hydrochloric acid and water. After drying with magnesium sulphate, the benzene was evaporated and the crude N, N-dimethyl-3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionic acid amide obtained in this way for analysis at 0.08 mm Hg and 1100 ° C. (temperature measured in the block) distilled.
A solution of 0.1 mol of crude N, N-dimethyl-3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionamide in 50 cms of dry ether was added to a suspension of 0.25 mol of finely powdered lithium aluminum hydride in 50 cms of dry ether Carefully added dropwise with stirring. After the addition was complete, the suspension was boiled with stirring and reflux for a further 4 hours, after which 50 cm of water were added to decompose the excess lithium aluminum hydride. The resulting suspension was mixed with 150 cms of sodium hydroxide solution, the ethereal layer was separated and the
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watery layer 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, white, crystalline 1-phenyl-1- (o-chlorophenyl) -3-dimethylaminopropanol- (1), F = 123 ° C., being obtained. The hydrochloride was obtained by means of an alcoholic hydrogen chloride solution and recrystallized from ethanol-ether; F = 191 C.
EMI2.1
Solution freed from methanol by evaporation, mixed with water and extracted with ether. After acidification with hydrochloric acid, the aqueous layer gave the crude 3-phenyl-3- (o-chlorophenyl) -3-hydroxypropionic acid, which was recrystallized from benzene petroleum ether; F = 1550C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU242120X | 1962-12-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AT242120B true AT242120B (en) | 1965-08-25 |
Family
ID=25559793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT867963A AT242120B (en) | 1962-12-03 | 1963-10-30 | Process for the preparation of 1-phenyl-1- (o-chlorophenyl) -3-dimethylaminopropanol- (1) |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT242120B (en) |
-
1963
- 1963-10-30 AT AT867963A patent/AT242120B/en active
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