CH265121A - Method for producing a local anesthetic. - Google Patents
Method for producing a local anesthetic.Info
- Publication number
- CH265121A CH265121A CH265121DA CH265121A CH 265121 A CH265121 A CH 265121A CH 265121D A CH265121D A CH 265121DA CH 265121 A CH265121 A CH 265121A
- Authority
- CH
- Switzerland
- Prior art keywords
- local anesthetic
- xylidide
- acid
- compound
- producing
- Prior art date
Links
- 239000003589 local anesthetic agent Substances 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 4
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008096 xylene Substances 0.000 description 3
- CZZZABOKJQXEBO-UHFFFAOYSA-N 2,4-dimethylaniline Chemical group CC1=CC=C(N)C(C)=C1 CZZZABOKJQXEBO-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- CDULGHZNHURECF-UHFFFAOYSA-N 2,3-dimethylaniline 2,4-dimethylaniline 2,5-dimethylaniline 2,6-dimethylaniline 3,4-dimethylaniline 3,5-dimethylaniline Chemical group CC1=CC=C(N)C(C)=C1.CC1=CC=C(C)C(N)=C1.CC1=CC(C)=CC(N)=C1.CC1=CC=C(N)C=C1C.CC1=CC=CC(N)=C1C.CC1=CC=CC(C)=C1N CDULGHZNHURECF-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- BLALBRWEAJQIIL-UHFFFAOYSA-N [Cl].CC(O)=O Chemical compound [Cl].CC(O)=O BLALBRWEAJQIIL-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- -1 halo acetic acid halide Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 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
- 238000001556 precipitation Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
Verfahren zur Herstellung eines Lokalanästhetikums. Gegenstand des vorliegenden Patentes ist ein Verfahren zur Herstellung eines Lokal- anästhetikums, welches dadurch gekennzeich- net ist, dass man eine den Rest.
EMI0001.0005
abgebende Verbindung, wie zum Beispiel das Xylidin selbst oder sein Hydrochlorid, mit einer das Radikal einer Halogenessigsäure ab gebenden Verbindung behandelt und das er haltene Halogenessigsäurexylidid mit Di- methylamin zum (N-Dimethyl-aminoacetyl)- xylidid-2,6 umsetzt.
Diese neue Verbindung kristallisiert in Form farbloser Täfelchen vom Schmelzpunkt 77 bis 790.
Die neue Verbindung besitzt eine rasche und gute Wirkung als lokales Anästhetikum, während ihre Toxizität verhältnismässig gering ist. Gut geeignet zur Anwendung als Lokal- anästhetikum sind auch die Salze dieser Sub stanz mit organischen oder anorganischen Säuren, z. B. Weinsäure, Zitronensäure, Salz säure. Besonders geeignet ist das Hydrochlo- rid. Dieses neue Lokalanästhetikum kann ohne Zusatz von Vasokonstringens angewendet wer den. Die wässerigen Lösungen seiner Salze sind besonders gut haltbar, auch in Verbin dung mit Adrenalin.
Die erste Stufe des Verfahrens, die Her stellung des Halogenessigsäure-xy lidids, kann zum Beispiel durch Einwirkung von Halogen essigsäurehalogenid, wie Chloressigsäurechlo- rid, auf vic. m-Xylidin in der Kälte oder auch durch Behandlung des Hydrochlorids des m- Xylidins mit Halogenessigsäureamid erfolgen.
Beispiel: 1 Mol vicinales m - Xylidiniumchlorid wird mit 1 Mol Chloracetamid innig ge mischt und langsam im ölbad auf 120 bis 1300C erwärmt. Die Mischung schmilzt an fangs, erstarrt jedoch wieder infolge von ab geschiedenem Salmiak. Die Erwärmung wird während einer Stunde fortgesetzt. Die Reak tionsmasse wird mit mit etwas Tierkohle ver setztem Xy lol ausgekocht.
Aus der filtrierten heissen Lösung kristallisiert bei Abkühlung Chlor essigsäure-xylidid aus, das gewünschten falls aus Xylol umkristallisiert werden kann.
1 Mol des erhaltenen Chloressigsäure-xyli- dids wird in 1000 cm3 trockenem Benzol ge löst. Zu der Lösung werden 2,5 bis 3 Mol Di- methylamin zugesetzt. Die Mischung wird im geschlossenen Gefäss bei<B>700</B> C 4 bis 5 Stunden erwärmt. Das abgeschiedene Dimethylamin- h.ydrochlorid wird abfiltriert. Die Benzol lösung wird zweimal mit 3n-Salzsäure durch geschüttelt, zuerst mit 800 cm' und dann mit 400 cm.
Die Säureextrakte werden vereinigt und mit 30 Jo iger Natronlauge versetzt, bis die -Ausfällung nicht weiter vermehrt wird. Die ausgefällte Substanz wird in Äther aufgenom men. Die Ätherlösung wird mit Pottasche ge trocknet, worauf das Lösungsmittel abgetrie ben wird. Das erhaltene rohe (N-Dimethyl- aminoacetyl)-xylidid-2,6 wird am einfachsten durch Umkristallisierung aus Xylol gereinigt.
Method for producing a local anesthetic. The subject of the present patent is a method for the production of a local anesthetic, which is characterized in that one the rest.
EMI0001.0005
The releasing compound, such as xylidine itself or its hydrochloride, is treated with a compound releasing the radical of a haloacetic acid and the haloacetic acid xylidide obtained is reacted with dimethylamine to form (N-dimethyl-aminoacetyl) -xylidide-2,6.
This new compound crystallizes in the form of colorless tablets with a melting point of 77 to 790.
The new compound has a quick and good effect as a local anesthetic while its toxicity is relatively low. The salts of this substance with organic or inorganic acids, eg. B. tartaric acid, citric acid, hydrochloric acid. Hydrochloride is particularly suitable. This new local anesthetic can be used without the addition of vasoconstrictors. The aqueous solutions of its salts are particularly durable, also in conjunction with adrenaline.
The first stage of the process, the Her position of the haloacetic acid xy lidids, can for example by the action of halo acetic acid halide, such as chloroacetic acid chloride, on vic. m-xylidine can be carried out in the cold or by treating the hydrochloride of m-xylidine with haloacetic acid amide.
Example: 1 mole of vicinal m-xylidinium chloride is intimately mixed with 1 mole of chloroacetamide and slowly heated to 120 to 130 ° C. in an oil bath. The mixture initially melts, but solidifies again as a result of the separated ammonia. The heating continues for an hour. The reaction mass is boiled with xylene mixed with a little animal charcoal.
From the filtered hot solution, chlorine acetic acid xylidide crystallizes out on cooling, which if desired can be recrystallized from xylene.
1 mol of the chloroacetic acid xylide obtained is dissolved in 1000 cm3 of dry benzene. 2.5 to 3 mol of dimethylamine are added to the solution. The mixture is heated in a closed vessel at <B> 700 </B> C for 4 to 5 hours. The separated dimethylamine hydrochloride is filtered off. The benzene solution is shaken twice with 3N hydrochloric acid, first at 800 cm and then at 400 cm.
The acid extracts are combined and mixed with 30% sodium hydroxide solution until the precipitation does not increase any further. The precipitated substance is taken up in ether. The ether solution is dried with potash, whereupon the solvent is removed. The crude (N-dimethylaminoacetyl) xylidide-2,6 obtained is most easily purified by recrystallization from xylene.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE497443 | 1943-07-15 | ||
| CH257878T | 1944-07-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH265121A true CH265121A (en) | 1949-11-15 |
Family
ID=25730140
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH265121D CH265121A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
| CH265118D CH265118A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
| CH265117D CH265117A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
| CH265119D CH265119A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH265118D CH265118A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
| CH265117D CH265117A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
| CH265119D CH265119A (en) | 1943-07-15 | 1944-07-29 | Method for producing a local anesthetic. |
Country Status (1)
| Country | Link |
|---|---|
| CH (4) | CH265121A (en) |
-
1944
- 1944-07-29 CH CH265121D patent/CH265121A/en unknown
- 1944-07-29 CH CH265118D patent/CH265118A/en unknown
- 1944-07-29 CH CH265117D patent/CH265117A/en unknown
- 1944-07-29 CH CH265119D patent/CH265119A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CH265117A (en) | 1949-11-15 |
| CH265119A (en) | 1949-11-15 |
| CH265118A (en) | 1949-11-15 |
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