CH364793A - Process for the preparation of new derivatives of anthranilic acid - Google Patents
Process for the preparation of new derivatives of anthranilic acidInfo
- Publication number
- CH364793A CH364793A CH56362A CH5636256A CH364793A CH 364793 A CH364793 A CH 364793A CH 56362 A CH56362 A CH 56362A CH 5636256 A CH5636256 A CH 5636256A CH 364793 A CH364793 A CH 364793A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- anthranilic acid
- new derivatives
- formula
- acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 3
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 title description 6
- IKCLCGXPQILATA-UHFFFAOYSA-N 2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1Cl IKCLCGXPQILATA-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- 150000001447 alkali salts Chemical class 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- -1 alkali metal salts Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- KCHLDNLIJVSRPK-UHFFFAOYSA-N 3-methylsulfanylaniline Chemical compound CSC1=CC=CC(N)=C1 KCHLDNLIJVSRPK-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241000530268 Lycaena heteronea Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
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 von neuen Derivaten der Anthranilsäure
Es wurde gefunden, dass man zu neuen, am Stickstoff durch einen m-Alkylmercapto-bzw. Aralkylmercapto-phenylrest substituierten Anthranilsäuren der Formel I
EMI1.1
worin R einen Alkylrest mit 1-4 Kohlenstoffatomen oder einen Aralkylrest bedeutet, gelangen kann, indem man Alkalisalze der o-Chlorbenzoesäure mit Aniline der Formel II
EMI1.2
kondensiert und aus den so erhaltenen Alkalisalzen der substituierten Anthranilsäuren die entsprechenden Säuren in Freiheit setzt.
Das erfindungsgemässe Verfahren wird beispielsweise so ausgeführt, dass man das Alkalisalz der o-Chlorbenzoesäure in einem geeigneten Lösungsmit- tel, z. B. einem höheren aliphatischen Alkohol, unter Rühren und Zusatz eines geeigneten Kondensationsmittels, z. B. Kupferpulver, mit dem Anilin der Formel II bei Zimmertemperatur oder erhöhter Temperatur (z. B. Siedetemperatur des Lösungsmittels) umsetzt. Nach beendigter Kondensation wird Soda zugesetzt, das Reaktionsprodukt durch Wasserdampfdestillation von flüchtigen Verunreinigungen befreit und aus dem Rückstand, der das Alkalisalz der substituierten Anthranilsäure enthält, die freie Säure durch Ansäuern ausgefällt.
Die nach dem vorliegen- den Verfahren hergestellten, bisher unbekannten Verbindungen sind bei Zimmertemperatur feste, leicht kristallisierende Substanzen. Sie sind wertvolle Zwischenprodukte für die Herstellung von Medikamenten. So liefern sie z. B. nach Decarboxylierung und anschliessender Behandlung'mit Schwefelungsmitteln, wie Schwefeldihalogeniden, Phenothiazine der Formel III
EMI1.3
die einerseits als Vulkanisationsbeschleuniger verwendet werden können, anderseits als Antihelmintika selbst wertvolle therapeutische Eigenschaften besitzen, die vor allem aber durch Substituierung mit geeigneten Gruppen am Stickstoff in stark wirksame sedative Neuroplegika und narkosepotenzierende Mittel umgewandelt werden können.
In den nachfolgenden Beispielen erfolgen alle Temperaturangaben in Celsius-Graden. Die Schmelzpunkte sind unkorrigiert und wurden mit Hilfe eines Apparates nach Thiele bestimmt.
Beispiel 1
46,5 g des Kaliumsalzes der o-Chlorbenzoesäure, 36,6 g m-Methylmercaptoanilin und 1,9 g Kupferpulver werden in 155 ml 4-Methylpentanol- (2) 5 Stunden am Rückfluss gekocht. Nach Zugabe von 280 ml 2n Sodalösung wird das erhaltene Gemisch etwa 1 Stunde mit Wasserdampf destilliert und anschliessend der erhaltene Rest mit 135 ml 18"/piger Salzsäure kongosauer gestellt. Die ausgefallene Car 40 45 50 55 60 65
5 10 15 20 25 30 bonsäure entstand in 8090 /0 Ausbeute und hatte nach Umkristallisieren aus 160 nit Benzol einen Schmelzpunkt von 139-141".
BeisDiele 2-8
Auf die gleiche Weise, wie in Beispiel 1 beschrieben, wurden die folgenden Verbindungen der Formel I hergestellt :
EMI2.1
Nr. R Smp. o C
EMI2.2
Nr. R Smp. oC
EMI2.3
Process for the preparation of new derivatives of anthranilic acid
It has been found that new, on nitrogen by an m-alkyl mercapto or. Aralkylmercapto-phenyl radical-substituted anthranilic acids of the formula I
EMI1.1
in which R denotes an alkyl radical with 1-4 carbon atoms or an aralkyl radical, can be obtained by adding alkali metal salts of o-chlorobenzoic acid with anilines of the formula II
EMI1.2
condenses and sets the corresponding acids free from the alkali metal salts of the substituted anthranilic acids thus obtained.
The inventive method is carried out, for example, that the alkali salt of o-chlorobenzoic acid in a suitable solvent, z. B. a higher aliphatic alcohol, with stirring and the addition of a suitable condensing agent, e.g. B. copper powder, with the aniline of the formula II at room temperature or elevated temperature (z. B. boiling point of the solvent). After the condensation has ended, soda is added, the reaction product is freed from volatile impurities by steam distillation and the free acid is precipitated from the residue, which contains the alkali metal salt of the substituted anthranilic acid, by acidification.
The previously unknown compounds produced by the present process are solid, easily crystallizing substances at room temperature. They are valuable intermediate products in the manufacture of medicines. So they deliver z. B. after decarboxylation and subsequent treatment with sulfurizing agents such as sulfur dihalides, phenothiazines of the formula III
EMI1.3
which can be used on the one hand as vulcanization accelerators, on the other hand as antihelmintics themselves have valuable therapeutic properties, which can be converted into highly effective sedative neuroplegics and anesthesia-potentiating agents primarily by substitution with suitable groups on nitrogen.
In the following examples, all temperatures are given in degrees Celsius. The melting points are uncorrected and were determined using a Thiele apparatus.
example 1
46.5 g of the potassium salt of o-chlorobenzoic acid, 36.6 g of m-methylmercaptoaniline and 1.9 g of copper powder are refluxed in 155 ml of 4-methylpentanol- (2) for 5 hours. After adding 280 ml of 2N soda solution, the mixture obtained is distilled with steam for about 1 hour and the residue obtained is then acidified to Congo with 135 ml of 18 "hydrochloric acid. The precipitated Car 40 45 50 55 60 65
5 10 15 20 25 30 bonsäure was formed in 8090/0 yield and had a melting point of 139-141 "after recrystallization from 160 n with benzene.
BeisDiele 2-8
In the same way as described in Example 1, the following compounds of formula I were prepared:
EMI2.1
No. R m.p. o C
EMI2.2
No. R m.p. oC
EMI2.3
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH56362A CH364793A (en) | 1956-04-18 | 1956-04-18 | Process for the preparation of new derivatives of anthranilic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH56362A CH364793A (en) | 1956-04-18 | 1956-04-18 | Process for the preparation of new derivatives of anthranilic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH364793A true CH364793A (en) | 1962-10-15 |
Family
ID=4520461
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH56362A CH364793A (en) | 1956-04-18 | 1956-04-18 | Process for the preparation of new derivatives of anthranilic acid |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH364793A (en) |
-
1956
- 1956-04-18 CH CH56362A patent/CH364793A/en unknown
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