CH314800A - Process for the preparation of 4-butylamino-salicylic acid - Google Patents
Process for the preparation of 4-butylamino-salicylic acidInfo
- Publication number
- CH314800A CH314800A CH314800DA CH314800A CH 314800 A CH314800 A CH 314800A CH 314800D A CH314800D A CH 314800DA CH 314800 A CH314800 A CH 314800A
- Authority
- CH
- Switzerland
- Prior art keywords
- butylamino
- preparation
- acid
- salicylic acid
- reaction
- Prior art date
Links
- FEEAGCZFKJMNDK-UHFFFAOYSA-N 4-(butylamino)-2-hydroxybenzoic acid Chemical compound CCCCNC1=CC=C(C(O)=O)C(O)=C1 FEEAGCZFKJMNDK-UHFFFAOYSA-N 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 claims description 4
- 229960004909 aminosalicylic acid Drugs 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- -1 n-butyl halide Chemical class 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 150000002484 inorganic compounds Chemical class 0.000 claims description 2
- 229910010272 inorganic material Inorganic materials 0.000 claims description 2
- 238000002844 melting Methods 0.000 claims description 2
- 230000008018 melting Effects 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- NBGAYCYFNGPNPV-UHFFFAOYSA-N 2-aminooxybenzoic acid Chemical class NOC1=CC=CC=C1C(O)=O NBGAYCYFNGPNPV-UHFFFAOYSA-N 0.000 description 2
- CWLKGDAVCFYWJK-UHFFFAOYSA-N 3-aminophenol Chemical compound NC1=CC=CC(O)=C1 CWLKGDAVCFYWJK-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003589 local anesthetic agent Substances 0.000 description 2
- 229960005015 local anesthetics Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- CQKPHJQTUGDTQR-UHFFFAOYSA-N 2-aminooxy-4-butylbenzoic acid Chemical compound C(CCC)C=1C=C(C(C(=O)O)=CC1)ON CQKPHJQTUGDTQR-UHFFFAOYSA-N 0.000 description 1
- 229940018563 3-aminophenol Drugs 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 230000001549 tubercolostatic effect Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von 4-Butylamino-salicylsäure
4-Monoalkylamino-salicylsäuren und 4 (Alono-alkyloxyalkyl)-amino-salicylsäuren der Formel
EMI1.1
in der R eine Alkyl-oder Alkyloxyalkylgruppe bedeutet, welche 2 oder mehr C-Atome in der am N-Atom gebundenen Alkylgruppe trägt, sind noch nicht beschrieben worden.
Man kann zu diesen alkylierten bzw. alkyl- oxyalkylierten Aminosalieylsäuren gelangen, indem man 4-Amino-salicylsäure (4-Amino-2- oxy-benzoesäure) mit einem unsubstituierten oder substituierten Alkylhalogenid oder Alkyl oxyalkylhalogenid, welches 2 od'er mehr, vornehmlieh 2-10 C-Atome in der am N-Atom gebundenen Alkylgruppe trägt, umsetzt. Zweck- rnässig werden als Halogenide die Bromide oder Jodide angewandt. Die Reaktion kann durch Umsetzung der Komponenten in Wasser und bzw. oder einem organischen Lösungs- mittel, zweckmässig bei erhöhter Temperatur, durchgefiihrt werden. Als organische Losungs- mittel sind insbesondere Alkohole geeignet.
Es ist wesentlich, dass die Reaktion bei Gegenwart von so viel Alkali oder Erdalkali durch- geführt wird, dass das Reaktionsmedium immer alkalisch bleibt. Damit erreieht man, dass die Zersetzungstendenz der 4-Amino-salicylsäure, welche bei Erhitzen in neutraler oder saurer Lösung sehr leicht in m-Amino-phenol und CO2 zerfällt, weitgehend zurückgedrängt wird.
Als Alkalien können die Oxyde, Hydroxyde, Carbonate und Bicarbonate der Alkali-und Erdalkalimetalle verwendet werden.
Die alkylierten bzw. alkyloxyalkylierten 4 Amino-salicylsäuren haben tuberkulostatisehe Eigensehaften und dienen ferner zur Herstellung wertvoller Therapeutica, wie z. B.
Lokalanästhetica.
Gegenstand des vorliegenden Patentes ist ein Verfahren zur Herstellung der 4-Butyl- amino-salicylsäure, welches dadurch gekennzeichnet ist, dass man 4-Amino-salicylsäure mit einem n-Butylhalogenid in Gegenwart einer alkalisch reagierenden anorganischen Verbindung und eines Lösungsmittls. umsetzt.
Als alkaliseh reagierende Verbindungen kommen z. B. Alkalien und Erdalkalien und als Lösungsmittel Wasser und organisehe Lö sungsmittel in Betracht. Die umsetzung erfolgt zweckmässig bei erhöhter Temperatur.
Beispiel
153 g 4-Amino-salieylsäure und 138 g Ka liumearbonat werden in 500 cm3 Wasser gelöst. Nach Zugabe von 103 g n-Butylbromid wird unter Rühren allmählich auf 80-85 erhitzt, und man hält das Reaktionsgemisch 3 Stunden bei dieser Temperatur. Naeh der Zugabe von 40 g Kaliumearbonat und 40 g n Butylbromid rührt man eine weitere Stunde bei 85 , kühlt ab und trennt von der untern Schicht ab. Die wässrige Losung wird bis auf einen pH-Wert von 4-5 angesäuert. Die ausfallende rohe 4-n-Butylamino-salievlsäure wird nach dem Troeknen aus Benzol umkristallisiert. Blättchen vom Schmelzpunkt 133 bis 134 .
Die 4-Butylamino-salicylsäure kann als Tuberkuloseheilmittel verwendet werden ; ferner ist sie ein wertvolles Zwisehenprodukt zur Herstellung von Lokalanästhetiea.
Process for the preparation of 4-butylamino-salicylic acid
4-monoalkylamino-salicylic acids and 4 (alono-alkyloxyalkyl) -amino-salicylic acids of the formula
EMI1.1
in which R denotes an alkyl or alkyloxyalkyl group which has 2 or more C atoms in the alkyl group bonded to the N atom have not yet been described.
These alkylated or alkyl-oxyalkylated aminosalicylic acids can be obtained by adding 4-aminosalicylic acid (4-amino-2-oxy-benzoic acid) with an unsubstituted or substituted alkyl halide or alkyl oxyalkyl halide, which is 2 or more, mainly 2 -10 C atoms in the alkyl group attached to the N atom carries, converts. The bromides or iodides are expediently used as halides. The reaction can be carried out by reacting the components in water and / or an organic solvent, expediently at elevated temperature. Alcohols are particularly suitable as organic solvents.
It is essential that the reaction is carried out in the presence of so much alkali or alkaline earth metal that the reaction medium always remains alkaline. This means that the tendency for 4-aminosalicylic acid to decompose, which easily breaks down into m-aminophenol and CO2 when heated in a neutral or acidic solution, is largely suppressed.
The oxides, hydroxides, carbonates and bicarbonates of the alkali and alkaline earth metals can be used as alkalis.
The alkylated or alkyloxyalkylated 4 amino-salicylic acids have tuberculostatic properties and are also used for the production of valuable therapeutics, such as. B.
Local anesthetics.
The subject of the present patent is a process for the preparation of 4-butyl-aminosalicylic acid, which is characterized in that 4-aminosalicylic acid is mixed with an n-butyl halide in the presence of an alkaline inorganic compound and a solvent. implements.
Compounds with an alkaline reaction are e.g. B. alkalis and alkaline earths and water and organic solvents as solvents. The reaction is expediently carried out at an elevated temperature.
example
153 g of 4-amino-salicic acid and 138 g of potassium carbonate are dissolved in 500 cm3 of water. After adding 103 g of n-butyl bromide, the mixture is gradually heated to 80-85 with stirring, and the reaction mixture is kept at this temperature for 3 hours. After the addition of 40 g of potassium carbonate and 40 g of n-butyl bromide, the mixture is stirred for another hour at 85, cooled and separated from the lower layer. The aqueous solution is acidified to a pH of 4-5. The precipitated crude 4-n-butylamino-salievic acid is recrystallized from benzene after drying. Leaflets with a melting point of 133 to 134.
4-Butylamino-salicylic acid can be used as a tuberculosis cure; Furthermore, it is a valuable intermediate product for the production of local anesthetics.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE314800X | 1951-08-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH314800A true CH314800A (en) | 1956-06-30 |
Family
ID=6147868
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH314800D CH314800A (en) | 1951-08-16 | 1952-07-14 | Process for the preparation of 4-butylamino-salicylic acid |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH314800A (en) |
-
1952
- 1952-07-14 CH CH314800D patent/CH314800A/en unknown
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