CH93751A - Process for the preparation of benzyl p-diethylaminomethylbenzoate. - Google Patents
Process for the preparation of benzyl p-diethylaminomethylbenzoate.Info
- Publication number
- CH93751A CH93751A CH93751DA CH93751A CH 93751 A CH93751 A CH 93751A CH 93751D A CH93751D A CH 93751DA CH 93751 A CH93751 A CH 93751A
- Authority
- CH
- Switzerland
- Prior art keywords
- acid
- ester
- water
- benzyl ester
- easily soluble
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- PNYHAYPCCJEXAM-UHFFFAOYSA-N CCN(CC)CC(C=C1)=CC=C1C(OCC1=CC=CC=C1)=O Chemical compound CCN(CC)CC(C=C1)=CC=C1C(OCC1=CC=CC=C1)=O PNYHAYPCCJEXAM-UHFFFAOYSA-N 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 6
- -1 methylbenzoic acid halide Chemical class 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- 230000003444 anaesthetic effect Effects 0.000 claims description 4
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
- KNOJLJBMIUUGJJ-UHFFFAOYSA-N CCC1(C=CC(CC)=CC1CN)C(OCC1=CC=CC=C1)=O Chemical compound CCC1(C=CC(CC)=CC1CN)C(OCC1=CC=CC=C1)=O KNOJLJBMIUUGJJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000005684 Liebig rearrangement reaction Methods 0.000 claims description 2
- 239000008896 Opium Substances 0.000 claims description 2
- 229930013930 alkaloid Natural products 0.000 claims description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000000155 melt Substances 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 229940053973 novocaine Drugs 0.000 claims description 2
- 229960001027 opium Drugs 0.000 claims description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 238000007127 saponification reaction Methods 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluenecarboxylic acid Natural products CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- CQQSQBRPAJSTFB-UHFFFAOYSA-N 4-(bromomethyl)benzoic acid Chemical compound OC(=O)C1=CC=C(CBr)C=C1 CQQSQBRPAJSTFB-UHFFFAOYSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229960001789 papaverine Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
Verfahren zur Darstellung des p-Diätlhylanminonmetlhylbenzoesäurebenzylesters. Gegenstand der vorliegenden Erfindung ist ein Verfahren zur Darstellung des p-Diätliyl- aminomethylbenzoesäurebenzylesters, welches darin besteht, dass rman auf p-Diäthylamino- benzoesäurehalogenide Benzylallkohol einwir ken lässt.
Der p-Diäthylaminonmethylbenzoesäureben- zylester bildet schön kristallisierte, in Wasser leicht lösliche Salze, deren wässerige Lösunr- gen, ohne dass eine Verseifung eintritt, län gere Zeit erhitzt werden können.
Der salzsaure p-Diäthylaminomethylbenrzoe- säurebenzylester schmilzt bei 166 , er ist sehr leicht und mit neutraler Reaktion in Wasser löslich. Sein Salzsäuregehalt entspricht der Formel (C2 H5) 2N - C112 - CsH4 - CO ³ 0 ³ CH2 C6H5 HCl.
Gegenüber den bereits bekannten Alkyl estern der Benzylamin-karbonsäuren (Liebigs Annalen der Chemie, Bd. 310, 1900, S.205), die ein kaum angedeutetes Anästlhesierungs- vermögen besitzen, erweist sich der p-Diäthyl- aminomethylbenzoesäurebenzyllester als Lokal- und Leitungsanästhetikum, dessen Wirkungs stärke derjenigen des Cocain und Novokain gleichhkommt. Ubei dies besitzt der Ester, ähnlich demn Opiumalkaloid Papaverin, die Fähigkeit krampfartig kontrahierte Organe zu entspannen.
Er soll in der Therapie Verwendung finden. Beispiel: 12Teilep-Diätlhylaminonmethylbenzoesäure- chlorhydrat, hergestellt aus p-Brommethy I- benzoesäure durch Erwärmen mit alkoholi scher Diäthylaminlösung, Abdestillieren des Alkohols, Aufnehmen mit Alkali, Entfernen des überschüssigen Diäthylamins, Ansäuern mit Salzsäure, Eindampfen zur Trockne und Extraktion des Reaktionsproduktes rmit abs. Allkolhol, werden mit 30 Teilen Thionylchlo- rid 1/2 Stunde erwärmt.
Das entstandene Chlorhydrat des p-Diäthylaminomethylberrzoe- säurechlorids, welches nach dem Abdestillie ren des Thionylchlorids hinterbleibt, wird nach und nach mit 14 Teilen Bernzylalkobol versetzt. Es tritt langsam Lösung ein. Nach 2I-stündigern Stehen wird Wasser zugegeben, arrsgeäther-t, die wässerig-saure Schicht alka lisch gemacht und einige Zeit geschüttelt, damit gegebenenfalls noch vorhandenes Säure chlorid zerstört wird.
Nach abermaligen i An, äthertn und Trocknen des Äthers fällt beim Versetzen mit alkoholischer Salzsäure ein bald kristallinisch erstarrendes Chlorhy drat aus, welches durch Umkristallisieren aus Alkohol, gegebenenfalls unter Zusatz von Äther, oder aus Essigester gereinigt werden kann.
Process for the preparation of p-diethylamino-methylbenzoic acid benzyl ester. The present invention relates to a method for preparing the p-diethylaminomethylbenzoic acid benzyl ester, which consists in allowing benzyl alcohol to act on p-diethylamino benzoic acid halides.
The p-diethylaminonmethylbenzoic acid benzyl ester forms nicely crystallized salts which are easily soluble in water, the aqueous solutions of which can be heated for a long time without saponification.
The hydrochloric acid p-diethylaminomethylbenzoic acid benzyl ester melts at 166, it is very easily and with a neutral reaction soluble in water. Its hydrochloric acid content corresponds to the formula (C2 H5) 2N - C112 - CsH4 - CO³ 0³ CH2 C6H5 HCl.
Compared to the already known alkyl esters of benzylamine carboxylic acids (Liebigs Annalen der Chemie, Vol. 310, 1900, p.205), which have a barely indicated anesthetic ability, the p-diethyl aminomethylbenzoic acid benzyl ester proves to be a local and line anesthetic, whose potency is equal to that of cocaine and novocaine. In addition, the ester, similar to the opium alkaloid papaverine, has the ability to relax spasmodically contracted organs.
It should be used in therapy. Example: 12-part p-diethylaminonmethylbenzoic acid chlorohydrate, produced from p-bromomethyl benzoic acid by heating with alcoholic diethylamine solution, distilling off the alcohol, taking up with alkali, removing the excess diethylamine, acidifying with hydrochloric acid, evaporating to dryness and extracting the reaction product. Allkolhol are heated with 30 parts of thionyl chloride for 1/2 hour.
The resulting chlorohydrate of p-diethylaminomethylberzoic acid chloride, which remains after the thionyl chloride has been distilled off, is gradually mixed with 14 parts of amberzyl alcohol. Solution occurs slowly. After standing for 21 hours, water is added, the ether is added, the aqueous-acidic layer is made alkaline and shaken for some time so that any acid chloride that may still be present is destroyed.
After renewed in, ethereal and drying of the ether, when mixed with alcoholic hydrochloric acid, a chlorohydrate which soon solidifies in crystalline form precipitates out, which can be purified by recrystallization from alcohol, optionally with the addition of ether, or from ethyl acetate.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH93751T | 1921-02-24 | ||
| CH93438T | 1921-02-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH93751A true CH93751A (en) | 1922-04-01 |
Family
ID=25704663
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH93751D CH93751A (en) | 1921-02-24 | 1921-02-24 | Process for the preparation of benzyl p-diethylaminomethylbenzoate. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH93751A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0208404B1 (en) * | 1985-05-29 | 1990-08-29 | Pfizer Inc. | Benzothiazine dioxide derivatives |
-
1921
- 1921-02-24 CH CH93751D patent/CH93751A/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0208404B1 (en) * | 1985-05-29 | 1990-08-29 | Pfizer Inc. | Benzothiazine dioxide derivatives |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2059923C3 (en) | 1-a-Isopropyl-o - [(N-methyl-N-homoveratryl) v-aminopropyl] -3,4-dimethoxyphenylacetonitrile, process for its preparation and pharmaceuticals containing it | |
| AT139454B (en) | Process for the preparation of alkamine esters. | |
| DE1925065C3 (en) | 1-phenylethyl-piperidinol (4) compounds, process for their preparation and pharmaceuticals containing them | |
| CH93751A (en) | Process for the preparation of benzyl p-diethylaminomethylbenzoate. | |
| DE1770408A1 (en) | Links-1-n-butyl-2 ', 6'-pipecoloxylidide and process for its preparation | |
| AT92388B (en) | Process for the preparation of aralkyl esters of benzylamine carboxylic acids. | |
| CH93438A (en) | Process for preparing benzyl p-dimethylaminomethylbenzoate. | |
| DE1593315C (en) | ||
| DE2065956C3 (en) | p-Acyloxime-phenoxyacetic acids and derivatives, processes for their preparation and pharmaceutical agents | |
| DE969245C (en) | Process for the production of new spasmolytically effective basic esters of ª ‡ -alkylated phenylacetic acids | |
| DE1292141B (en) | Trisubstituted acrylic acids, their alkali salts and a process for their preparation | |
| DE522064C (en) | Process for the preparation of Monoalkoxyaminobenzoesaeurealkaminestern | |
| DE586247C (en) | Process for the production of basic esters of fatty acids | |
| DE934103C (en) | Process for the production of cyclooctylated alkyl acetic acids with a strong cholagogue effect | |
| DE2523208C3 (en) | Thienylacetic acid esters, a process for their preparation and pharmaceuticals | |
| DE1593315B1 (en) | 9-isopropylidene-9,10-dihydroanthracene-10-carboxylic acid-ß-diaethylamino-ethyl ester, their salts and process for their preparation | |
| DE531363C (en) | Process for the preparation of basic esters of substituted quinoline-4-carboxylic acids | |
| DE2551283C3 (en) | Monofumaric acid salt of 3-pyridylmethyl nicotinate and process for its preparation | |
| DE1802656B2 (en) | 3,3-Diphenylpropylaminoalkanol esters, processes for their preparation and pharmaceuticals containing these compounds | |
| AT227256B (en) | Process for the production of new aminoindanes and their salts | |
| DE1170417C2 (en) | PROCESS FOR THE PRODUCTION OF A DIPHENYL-BUTYLAMINE WITH THE CORONARY VASCULAR EXPANSION EFFECT | |
| DE1768406C (en) | Phenylacetyl hydroxamic acids. Eliminated from: 1280254 | |
| CH92526A (en) | Process for the preparation of benzyl p-diethylaminomethylbenzoate. | |
| AT149360B (en) | Process for the preparation of esters of 2-phenylquinolinearboxylic acids- (4). | |
| AT216499B (en) | Process for the preparation of β- (4-methoxybenzoyl) -β-haloacrylic acids |