CH377801A - Process for the preparation of new N-arylsulfonylcarbamic acid derivatives - Google Patents
Process for the preparation of new N-arylsulfonylcarbamic acid derivativesInfo
- Publication number
- CH377801A CH377801A CH123160A CH123160A CH377801A CH 377801 A CH377801 A CH 377801A CH 123160 A CH123160 A CH 123160A CH 123160 A CH123160 A CH 123160A CH 377801 A CH377801 A CH 377801A
- Authority
- CH
- Switzerland
- Prior art keywords
- isocyanate
- formula
- acid derivatives
- preparation
- new
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 4
- 239000002253 acid Substances 0.000 title description 2
- -1 alkali metal salt Chemical class 0.000 claims description 19
- AFFPZJFLSDVZBV-UHFFFAOYSA-N 2-(trifluoromethyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1C(F)(F)F AFFPZJFLSDVZBV-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000012948 isocyanate Substances 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Chemical group 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Chemical group 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 claims description 2
- 150000002513 isocyanates Chemical class 0.000 claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001447 alkali salts Chemical class 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- ILYYQBMUPMMTHV-UHFFFAOYSA-N 4-chloro-3-(trifluoromethyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 ILYYQBMUPMMTHV-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KTKDYVVUGTXLJK-UHFFFAOYSA-N 1,1-dipropylurea Chemical compound CCCN(C(N)=O)CCC KTKDYVVUGTXLJK-UHFFFAOYSA-N 0.000 description 1
- AQSQFWLMFCKKMG-UHFFFAOYSA-N 1,3-dibutylurea Chemical compound CCCCNC(=O)NCCCC AQSQFWLMFCKKMG-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ZUTVRDMZQSHCID-UHFFFAOYSA-N 3-(trifluoromethyl)benzenesulfonamide Chemical group NS(=O)(=O)C1=CC=CC(C(F)(F)F)=C1 ZUTVRDMZQSHCID-UHFFFAOYSA-N 0.000 description 1
- TVHXQQJDMHKGGK-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 TVHXQQJDMHKGGK-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- RJNJWHFSKNJCTB-UHFFFAOYSA-N benzylurea Chemical compound NC(=O)NCC1=CC=CC=C1 RJNJWHFSKNJCTB-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002218 hypoglycaemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/52—Y being a hetero atom
- C07C311/54—Y being a hetero atom either X or Y, but not both, being nitrogen atoms, e.g. N-sulfonylurea
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von neuen N-Arylsulfonylcarbaminsäure-derivaten
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von neuen N-Arylsulfonyl-carbaminsäure-derivaten mit wertvollen pharmakologischen Eigenschaften.
Es wurde gefunden, dass N-Arylsulfonyl-carbaminsäure-derivate der Formel I,
EMI1.1
worin R einen Alkyl-, Alkenyl-, Cycloalkyl- oder Aralkylrest, Y Wasserstoff, Fluor, Chlor, Brom oder eine Methylgruppe bedeuten, das heisst N'-substituierte N- Trifluormethylbenzolsulfonyl -harnstoffe eine stark hypoglykämische Wirksamkeit besitzen und sich für die perorale Behandlung von Diabetes mellitus eignen.
Man stellt die oben definierten Verbindungen her, indem man ein Trifluormethylbenzolsulfonamid der Formel II,
EMI1.2
mit einem Alkyl-, Alkenyü, Cycloalkyl- oder Aralkylisocyanat der Formel III,
R-N=C=O (III) gegebenenfalls in Gegenwart eines Kondensationsmittels umsetzt. Als Kondensationsmittel für das genannte Herstellungsverfahren können basische Kondensationsmittel wie z. B. Alkalialkoholate, Pyridin oder Triäthylamin Verwendung finden. Man kann die Trifluormethylbenzolsulfonamide auch vor der Umsetzung durch Behandlung mit einer Alkaliverbindung in ein Alkalisalz überführen und, anstelle der freien Sulfonamide in Gegenwart eines basischen Kondensationsmittels, deren vorgebildete Alkalisalze zur Umsetzung verwenden.
Als Trifluormethylbenzolsulfonamide der Formel II kommen insbesondere das 3-Trifluormethyl- und das 4-Trifluormethylbenzolsulfonamid sowie das 3-Trifluormethyl-4- chlor-benzolsulfonamid in Betracht. Diese lassen sich beispielsweise mit dem Athyl, n-Propyl-, Isopropyl-, n-Butyl-, Isobutyl-, sek. Butyl-, n-Amyl-, Isoamyl-, n-Hexyl-, fl-Methyl-pentyl-, n-Octyl- 4-Äthyl-hexyl-, n-Dodecyl-, Allyl-, Crotyl-, Methallyl-,
Cyclopentyl-, Cyclohexyl- Benzyl p-Phenyläthyl-oder y-Phenyl-propyl-isocyanat umsetzen.
Die erfindungsgemäss erhaltenen Verbindungen der Formel I lassen sich in üblicher Weise in beständige wasserlösliche Alkalisalze überführen.
In den nachfolgenden Beispielen bedeuten Teile Gewichtsteile; diese verhalten sich zu Volumteilen wie g zu cm3. Die Temperaturen sind in Celsiusgraden angegeben.
Beispiel I
22,5 Teile 3 - Triflnormethyl - benzolsulfonamid werden in 100 Volumteilen Aceton gelöst und mit 20 Volumteilen 5n Natronlauge versetzt. Hierauf werden 9 Teile n-Propylisocyanat hinzugefügt und das Gemisch 4 Stunden unter Rückfluss gekocht. Das Aceton wird abdestilliert und die eingeengte Lösung mit Wasser verdünnt. Wenig unlösliches Nebenprodukt (Dipropylharnstoff) wird abfiltriert und das gewünschte Reaktionsprodukt mit verdünnter Salzsäure ausgefällt. Der rohe N-(3-Trifluormethylbenzolsulfonyl) -N'-n-propyl-harnstoff wird durch Umkristallisieren aus Alkohol gereinigt und schmilzt bei 144,5145,50.
Analog werden z. B. der N-(3-Trifluormethyl-benzolsulfonyl)-
N'-n-butylharnstoff, Smp. 114,5-115,5", N-(3-Trifluormethyl-benzolsulfonyl)-
N'-isobutylharnstoff, Smp. 123,5",
N-(3 -Trifluormethyl-benzolsulfonyl)
N'-isoamylharnstoff, N-(3 -Tnfluormethyi-benzolsulfonyl)-
N'-cyclopentylharnstoff, Smp. 119 , N-(3-Trifluormethyl-benzolsulfonyl)-
N'-cyclohexylharnstoff, Smp. 133 und der N-(3-Trifluormethyi-benzolsulfonyl)-
N'-benzylharnstoff erhalten.
Beispiel 2
25,9 Teile 3-Trifluormethyl-4-chlor-benzolsulfon- amid werden in 200 Volumteilen Aceton gelöst und mit 20 Volumteilen 5n Natronlauge versetzt. 11 Teile n-Butylisocyanat werden hinzugefügt, und das Gemisch wird kräftig geschüttelt. Nach vierstündigem Erhitzen unter Rückfluss wird das Reaktionsgemisch durch Abdestillieren von Aceton eingeengt und mit Wasser verdünnt. Das unlösliche Nebenprodukt (Dibutylharnstoff) wird abfiltriert und aus der klaren Lösung durch Ansäuern mit verdünnter Salzsäure der gewünschte NT-(3-Trifluormethyl-4-chlor- benzolsulfonyl)-N'-n-butylharnstoff ausgefällt. Durch Umkristallisieren aus Alkohol erhält man das reine Produkt vom Smp. 151,5".
Analog wird z. B. der N-(3-Trifluormethyl-4 chlor - benzolsulfonyl) - N'-cyclohexylharnstoff erhalten, vom Smp. 135".
Process for the preparation of new N-arylsulfonylcarbamic acid derivatives
The present invention relates to a process for the preparation of new N-arylsulfonyl-carbamic acid derivatives with valuable pharmacological properties.
It has been found that N-arylsulfonyl-carbamic acid derivatives of the formula I,
EMI1.1
where R is an alkyl, alkenyl, cycloalkyl or aralkyl radical, Y is hydrogen, fluorine, chlorine, bromine or a methyl group, that is, N'-substituted N-trifluoromethylbenzenesulfonylureas have a strong hypoglycemic activity and are suitable for the oral treatment of Diabetes mellitus.
The compounds defined above are prepared by adding a trifluoromethylbenzenesulfonamide of the formula II,
EMI1.2
with an alkyl, alkenyl, cycloalkyl or aralkyl isocyanate of the formula III,
R-N = C = O (III) optionally reacted in the presence of a condensing agent. As a condensation agent for the manufacturing process mentioned, basic condensation agents such as. B. find alkali metal alcoholates, pyridine or triethylamine use. The trifluoromethylbenzenesulfonamides can also be converted into an alkali salt prior to the reaction by treatment with an alkali compound and, instead of the free sulfonamides in the presence of a basic condensing agent, their preformed alkali salts can be used for the reaction.
Particularly suitable trifluoromethylbenzenesulfonamides of the formula II are 3-trifluoromethyl- and 4-trifluoromethylbenzenesulfonamide and also 3-trifluoromethyl-4-chlorobenzenesulfonamide. These can be, for example, with the ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec. Butyl-, n-amyl-, isoamyl-, n-hexyl-, fl-methyl-pentyl-, n-octyl- 4-ethyl-hexyl-, n-dodecyl-, allyl-, crotyl-, methallyl-,
Implement cyclopentyl, cyclohexyl benzyl, p-phenylethyl or y-phenyl propyl isocyanate.
The compounds of the formula I obtained according to the invention can be converted into stable water-soluble alkali salts in the customary manner.
In the following examples, parts mean parts by weight; these are related to parts of volume as g to cm3. The temperatures are given in degrees Celsius.
Example I.
22.5 parts of 3-trifinormethylbenzenesulfonamide are dissolved in 100 parts by volume of acetone, and 20 parts by volume of 5N sodium hydroxide solution are added. 9 parts of n-propyl isocyanate are then added and the mixture is refluxed for 4 hours. The acetone is distilled off and the concentrated solution is diluted with water. Little insoluble by-product (dipropylurea) is filtered off and the desired reaction product is precipitated with dilute hydrochloric acid. The crude N- (3-trifluoromethylbenzenesulfonyl) -N'-n-propylurea is purified by recrystallization from alcohol and melts at 144.5145.50.
Analog are z. B. the N- (3-trifluoromethyl-benzenesulfonyl) -
N'-n-butylurea, m.p. 114.5-115.5 ", N- (3-trifluoromethyl-benzenesulfonyl) -
N'-isobutylurea, m.p. 123.5 ",
N- (3-trifluoromethyl-benzenesulfonyl)
N'-isoamylurea, N- (3 -tnfluoromethylbenzenesulfonyl) -
N'-cyclopentylurea, m.p. 119, N- (3-trifluoromethyl-benzenesulfonyl) -
N'-cyclohexylurea, m.p. 133 and the N- (3-trifluoromethylbenzenesulfonyl) -
Obtained N'-benzylurea.
Example 2
25.9 parts of 3-trifluoromethyl-4-chlorobenzenesulfonamide are dissolved in 200 parts by volume of acetone, and 20 parts by volume of 5N sodium hydroxide solution are added. 11 parts of n-butyl isocyanate are added and the mixture is shaken vigorously. After heating under reflux for four hours, the reaction mixture is concentrated by distilling off acetone and diluted with water. The insoluble by-product (dibutylurea) is filtered off and the desired NT- (3-trifluoromethyl-4-chlorobenzenesulfonyl) -N'-n-butylurea is precipitated from the clear solution by acidification with dilute hydrochloric acid. Recrystallization from alcohol gives the pure product with a melting point of 151.5 ".
Analog is z. B. obtained the N- (3-trifluoromethyl-4 chloro-benzenesulfonyl) -N'-cyclohexylurea, with a melting point of 135 ".
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH123160A CH377801A (en) | 1960-02-04 | 1960-02-04 | Process for the preparation of new N-arylsulfonylcarbamic acid derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH123160A CH377801A (en) | 1960-02-04 | 1960-02-04 | Process for the preparation of new N-arylsulfonylcarbamic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH377801A true CH377801A (en) | 1964-05-31 |
Family
ID=4205543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH123160A CH377801A (en) | 1960-02-04 | 1960-02-04 | Process for the preparation of new N-arylsulfonylcarbamic acid derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH377801A (en) |
-
1960
- 1960-02-04 CH CH123160A patent/CH377801A/en unknown
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