DE1543885B2 - PROCESS FOR THE PREPARATION OF 2-METHOXY-4-AMINO-5-CHLOROBENZOIC ACID METHYLESTER - Google Patents
PROCESS FOR THE PREPARATION OF 2-METHOXY-4-AMINO-5-CHLOROBENZOIC ACID METHYLESTERInfo
- Publication number
- DE1543885B2 DE1543885B2 DE19661543885 DE1543885A DE1543885B2 DE 1543885 B2 DE1543885 B2 DE 1543885B2 DE 19661543885 DE19661543885 DE 19661543885 DE 1543885 A DE1543885 A DE 1543885A DE 1543885 B2 DE1543885 B2 DE 1543885B2
- Authority
- DE
- Germany
- Prior art keywords
- amino
- methoxy
- preparation
- chlorobenzoic acid
- acid methylester
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/59—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C205/60—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms in ortho-position to the carboxyl group, e.g. nitro-salicylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- 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
- C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Footwear And Its Accessory, Manufacturing Method And Apparatuses (AREA)
Description
Die Erfindung betrifft ein Verfahren zur Herstellung von 2-Methoxy-4-amino-5-chlorbenzoesäuremethylester. The invention relates to a process for the preparation of 2-methoxy-4-amino-5-chlorobenzoic acid methyl ester.
Die nach dem Verfahren der Erfindung hergestellte Verbindung ist ein wertvolles Zwischenprodukt zur Herstellung von N-(Diäthylaminoäthyl)-2-methoxy-4-amino-5-chlorbenzamid, das als wirksames Arzneimittel mit analgetischer, antisepasmodischer, sedativer, anästhetischer und antiemetischer Wirkung aus der belgischen Patentschrift 620 543 bekannt ist.The compound prepared by the process of the invention is a valuable intermediate for Production of N- (diethylaminoethyl) -2-methoxy-4-amino-5-chlorobenzamide, that as an effective drug with analgesic, antisepasmodic, sedative, anesthetic and antiemetic effects from the Belgian patent 620 543 is known.
Das Verfahren der Erfindung ist dadurch gekennzeichnet, daß man 4-amino-5-chIorsalicylsäure in Gegenwart von alkalisch reagierenden Verbindungen eines Alkali- oder Erdalkalimetalls mit einem Methylsulfat oder einem Methylhalogenid alkyliert.The method of the invention is characterized in that 4-amino-5-chlorosalicylic acid in the presence of alkaline compounds of an alkali or alkaline earth metal with a methyl sulfate or a methyl halide alkylated.
Ein besonderer Vorteil des Verfahrens der Erfindung ist, daß nahezu ausschließlich O-Alkalierungsprodukte gebildet werden. Dieser Reaktionsverlauf ist überraschend, da aus den schweizerischen Patentschriften 310 076, 310 077 und 314 800 bekannt ist, daß p-Aminosalicylsäure von Alkalhalogeniden an der Aminogruppe alkyliert wird.A particular advantage of the process of the invention is that almost exclusively O-alkalization products are formed. This course of the reaction is surprising, since it can be found in the Swiss patents 310 076, 310 077 and 314 800 it is known that p-aminosalicylic acid is obtained from alkali halides on the amino group is alkylated.
Das im Verfahren der Erfindung verwendete Ausgangsprodukt, 4-Amino-5-chlorsalicylsäure, kann hergestellt werden, indem man 3-Amino-4-chlorphenol in Anwesenheit von wasserfreiem Kaliumcarbonat mit Kohlendioxid unter erhöhtem Druck im Autoklav umsetzt.The starting material used in the process of the invention, 4-amino-5-chlorosalicylic acid, can be prepared be done by using 3-amino-4-chlorophenol in the presence of anhydrous potassium carbonate Reacts carbon dioxide under increased pressure in the autoclave.
Als Alkylierungsmittel können erfindungsgemäß -M'biio- oder Dimethylsulfat oder Alkylhalogenide, wie .'Methylchlorid, verwendet werden. Als alkalisch reagie^rerßle-Verbindungen eines Alkali- oder Erdalkalimejtälis?werden erfindungsgemäß Alkalihydroxide, Erdalkälihydroxide, Alkalicarbonate, oder Erdalkalicarbonate verwendet>Die.Reaktion kann in Anwesenheit oder Abwesenheit eines Lösungsmittels durchgeführt werden.According to the invention, -M'biio- or dimethyl sulfate or alkyl halides, such as .'Methyl chloride, can be used as alkylating agents. As alkaline-reactive compounds of an alkali or alkaline earth metal ? alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates or alkaline earth metal carbonates are used according to the invention> The reaction can be carried out in the presence or absence of a solvent.
Wenn man die Reaktion in einem Lösungsmittel ausführt, so besteht für dieses, falls es nicht an der Reaktion teilnimmt, keine besondere Beschränkung. Als Lösungsmittel können Aceton, Äther, aromatische Kohlenwasserstoffe oder Dimethylformamid verwendet werden, wobei man zweckmäßigerweise bei Verwendung von Mono- oder Dimethylsulfat Aceton oder Äther und bei Verwendung von Alkylhalogeniden aromatische Kohlenwasserstoffe oder Dimethylformamid einsetzt.If the reaction is carried out in a solvent, then there is for this, if it is not, the reaction participates, no particular restriction. As a solvent, acetone, ether, aromatic Hydrocarbons or dimethylformamide are used be, advantageously when using mono- or dimethyl sulfate or acetone Ether and, if alkyl halides are used, aromatic hydrocarbons or dimethylformamide begins.
Das Verfahren gemäß der Erfindung wird im allgemeinen unter Erhitzen unter Rückfluß durchgeführt.The process according to the invention is generally carried out with refluxing.
Das Verfahren der Erfindung wird im folgenden an Hand eines Ausführungsbeispiels näher erläutert.The method of the invention is explained in more detail below using an exemplary embodiment.
Zu einer Lösung von 1,0 g 4-Amino-5-chlorsalicylsäure in 50 cm3 absoluten Aceton werden 1,6 g wasserfreies Kaliumcarbonat unter Rühren und Wasserausschluß zugegeben. Außerdem fügt man 1,5 g Dimethylsulfat hinzu. Das Gemisch wird 15 Stunden unter Rückfluß gerührt und dann filtriert. Das Filtrat wird mit Aktivkohle behandelt und das Lösungsmittel abdestilliert. Der Rückstand wird aus wäßrigem Methanol umkristallisiert. Man erhält l,04g2-Methoxy-4-amino-5-chlorbenzoesäuremethylester in Form von farblosen Kristallen mit einem Schmelzpunkt von 135 bis 137° C. Die Ausbeute beträgt 91 %.1.6 g of anhydrous potassium carbonate are added with stirring and with exclusion of water to a solution of 1.0 g of 4-amino-5-chlorosalicylic acid in 50 cm 3 of absolute acetone. In addition, 1.5 g of dimethyl sulfate are added. The mixture is stirred under reflux for 15 hours and then filtered. The filtrate is treated with activated charcoal and the solvent is distilled off. The residue is recrystallized from aqueous methanol. 1.04g of methyl 2-methoxy-4-amino-5-chlorobenzoate is obtained in the form of colorless crystals with a melting point of 135 ° to 137 ° C. The yield is 91%.
AHaIySe(C9H10O3NCl):AHaIySe (C 9 H 10 O 3 NCl):
Berechnet C 50,13, H 4,67, N 6,49, Cl 16,44%
Gefunden C 50,17, H 4,64, N 6,46, Cl 16,41 %Calculated C 50.13, H 4.67, N 6.49, Cl 16.44%
Found C 50.17, H 4.64, N 6.46, Cl 16.41%
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7613165 | 1965-12-10 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE1543885A1 DE1543885A1 (en) | 1970-01-02 |
| DE1543885B2 true DE1543885B2 (en) | 1973-08-02 |
| DE1543885C3 DE1543885C3 (en) | 1974-02-28 |
Family
ID=13596371
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1543885A Expired DE1543885C3 (en) | 1965-12-10 | 1966-12-02 | Process for the preparation of 2-methoxy ^ -amino-S-chlorobenzoic acid methyl ester |
Country Status (12)
| Country | Link |
|---|---|
| BE (1) | BE690476A (en) |
| BR (1) | BR6685258D0 (en) |
| CH (1) | CH486415A (en) |
| CS (1) | CS150934B2 (en) |
| DE (1) | DE1543885C3 (en) |
| ES (1) | ES334733A1 (en) |
| FI (1) | FI48066C (en) |
| FR (1) | FR1504227A (en) |
| GB (1) | GB1159938A (en) |
| IL (1) | IL26947A (en) |
| NO (1) | NO132956C (en) |
| OA (1) | OA02685A (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102311357B (en) * | 2011-10-17 | 2014-01-08 | 上海安诺芳胺化学品有限公司 | Preparation method of 2-hydroxy-4-aminobenzoic acid |
-
1966
- 1966-11-25 IL IL26947A patent/IL26947A/en unknown
- 1966-11-30 BE BE690476D patent/BE690476A/xx not_active IP Right Cessation
- 1966-11-30 FI FI663184A patent/FI48066C/en active
- 1966-12-02 DE DE1543885A patent/DE1543885C3/en not_active Expired
- 1966-12-06 ES ES0334733A patent/ES334733A1/en not_active Expired
- 1966-12-07 CS CS7793A patent/CS150934B2/cs unknown
- 1966-12-08 NO NO165905A patent/NO132956C/no unknown
- 1966-12-08 FR FR86769A patent/FR1504227A/en not_active Expired
- 1966-12-09 BR BR185258/66A patent/BR6685258D0/en unknown
- 1966-12-09 CH CH1762266A patent/CH486415A/en not_active IP Right Cessation
- 1966-12-10 OA OA52690A patent/OA02685A/en unknown
- 1966-12-12 GB GB55530/66A patent/GB1159938A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| DE1543885C3 (en) | 1974-02-28 |
| BE690476A (en) | 1967-05-30 |
| DE1543885A1 (en) | 1970-01-02 |
| FI48066B (en) | 1974-02-28 |
| ES334733A1 (en) | 1967-10-16 |
| NO132956B (en) | 1975-11-03 |
| FR1504227A (en) | 1967-12-01 |
| GB1159938A (en) | 1969-07-30 |
| NO132956C (en) | 1976-02-11 |
| BR6685258D0 (en) | 1973-12-04 |
| CH486415A (en) | 1970-02-28 |
| CS150934B2 (en) | 1973-09-17 |
| IL26947A (en) | 1970-12-24 |
| FI48066C (en) | 1974-06-10 |
| OA02685A (en) | 1970-12-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) | ||
| E77 | Valid patent as to the heymanns-index 1977 | ||
| 8339 | Ceased/non-payment of the annual fee |