CH355140A - Process for the preparation of sulfamidobenzoic acid esters - Google Patents
Process for the preparation of sulfamidobenzoic acid estersInfo
- Publication number
- CH355140A CH355140A CH355140DA CH355140A CH 355140 A CH355140 A CH 355140A CH 355140D A CH355140D A CH 355140DA CH 355140 A CH355140 A CH 355140A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- acid esters
- sulfamidobenzoic
- formula
- denote
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 6
- 150000002148 esters Chemical class 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
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000126 substance Substances 0.000 description 5
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- HWAQOZGATRIYQG-UHFFFAOYSA-N 4-sulfobenzoic acid Chemical compound OC(=O)C1=CC=C(S(O)(=O)=O)C=C1 HWAQOZGATRIYQG-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- SBYTWPFOSOWXSM-UHFFFAOYSA-N 1-(cyclohexylamino)ethanol;hydrochloride Chemical compound Cl.CC(O)NC1CCCCC1 SBYTWPFOSOWXSM-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 150000003973 alkyl amines Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229960004050 aminobenzoic acid Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- DGLFSNZWRYADFC-UHFFFAOYSA-N chembl2334586 Chemical group C1CCC2=CN=C(N)N=C2C2=C1NC1=CC=C(C#CC(C)(O)C)C=C12 DGLFSNZWRYADFC-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- WEHWNAOGRSTTBQ-UHFFFAOYSA-N dipropylamine Chemical compound CCCNCCC WEHWNAOGRSTTBQ-UHFFFAOYSA-N 0.000 description 1
- -1 ester salt Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
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 Sulfamidobenzoesäureestern
Es ist z.B. aus der norwegischen Patentschrift Nr. 80663 bekannt, dass Sulfamidobenzoesäuren der Formel
EMI1.1
in der R und R' Alkylgruppen bedeuten, die zusammen mindestens 5 und höchstens 8 Kohlenstoffatome aufweisen, eine blockierende Wirkung auf den Nierentubulus ausüben. Durch diese Wirkung wird die Aussonderung gewisser therapeutisch wertvoller Stoffe, wie z. B. von Penicillin, Sulfonamiden und pAmino- benzoesäure, verzögert und diese Substanzen erhalten hierdurch höhere Blutwerte.
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von Sulfamidobenzoesäureestern der Fomel
EMI1.2
in der R und R'Wasserstoff oder Alkylgruppen bedeuten und zusammen mindestens 4 und höchstens 10 Kohlenstoffatome aufweisen, R1 und R2 entweder einzeln Wasserstoff, eine Alkylgruppe, eine Cyclohexylgruppe oder eine Benzylgruppe oder zusammen mit dem Stickstoff einen Piperidin- oder Morpholinring bedeuten, und n 2 oder 3 ist, das dadurch gekennzeichnet ist, dass man eine Verbindung der Formel
EMI1.3
mit einem entsprechenden primären oder sekundären Alkylamin umsetzt. Das erfindungsgemäss zu verwendende Ausgangsmaterial wird z.B. erhalten, indem man das Dichlorid der p-Sulfobenzoesäure mit einer äquivalenten Menge des Aminoalkohols HO(CH2)nNR1R2 umsetzt.
Es hat sich gezeigt, dass die erfindungsgemäss erhaltenen Stoffe die Eigenschaft haben, den vorher genannten tubulusblockierenden Effekt in zumindest gleichem Ausmass auszuüben wie die Säuren, die zur Bildung dieser Stoffe gemäss der Erfindung angewendet werden. Diese Stoffe bilden mit Penicillin sehr schwerlösliche Salze.
Beispiel
240 Gewichtsteile in Toluol suspendierter p-Sulfobenzoesäure werden mit 166 Gewichtsteilen Phosphorpentachlorid während einer Stunde bei 90" chloriert. Danach lässt man die Chloridlösung mit einer äquivalenten Menge Cyclohexylaminoäthanol-hydrochlorid in Toluol reagieren. Nach 48 Stunden wird die Reaktionsmischung bei 400 mit Eiswasser gekühlt, und kaltes Wasser wird zugesetzt. Das Toluol wird abgeschieden und das Estersalz des Sulfochlorids während Kühlung bei 10 bis 15 einer Suspension von 150 Gewichtsteilen Dipropylamin in 5 % Lauge unter Umrühren zugeführt. Der gebildete Alkylester wird aus dem Wasser mit Ather extrahiert.
Nach Reinigung durch erneute Ausscheidung erhält man p-(N,N-Dipropyl-sulfamido) - benzoesäure-cyclohexyl- aminoäthylester.
Process for the preparation of sulfamidobenzoic acid esters
It is e.g. from Norwegian patent specification No. 80663 known that sulfamidobenzoic acids of the formula
EMI1.1
in which R and R 'denote alkyl groups which together have at least 5 and at most 8 carbon atoms exert a blocking effect on the renal tubule. This effect prevents certain therapeutically valuable substances, such as B. penicillin, sulfonamides and p-amino benzoic acid, and these substances get higher blood values as a result.
The present invention relates to a process for the preparation of sulfamidobenzoic acid esters of the formula
EMI1.2
in which R and R 'denote hydrogen or alkyl groups and together have at least 4 and at most 10 carbon atoms, R1 and R2 either individually denote hydrogen, an alkyl group, a cyclohexyl group or a benzyl group or together with the nitrogen denote a piperidine or morpholine ring, and n 2 or 3, which is characterized in that one is a compound of the formula
EMI1.3
with a corresponding primary or secondary alkylamine. The starting material to be used in the present invention is e.g. obtained by reacting the dichloride of p-sulfobenzoic acid with an equivalent amount of the amino alcohol HO (CH2) nNR1R2.
It has been shown that the substances obtained according to the invention have the property of exerting the aforementioned tubular-blocking effect to at least the same extent as the acids which are used to form these substances according to the invention. These substances form very poorly soluble salts with penicillin.
example
240 parts by weight of p-sulfobenzoic acid suspended in toluene are chlorinated with 166 parts by weight of phosphorus pentachloride for one hour at 90 ". The chloride solution is then allowed to react with an equivalent amount of cyclohexylaminoethanol hydrochloride in toluene. After 48 hours, the reaction mixture is cooled at 400 with ice water and Cold water is added, the toluene is separated off and the ester salt of the sulfochloride is added, while cooling at 10 to 15, to a suspension of 150 parts by weight of dipropylamine in 5% caustic solution with stirring. The alkyl ester formed is extracted from the water with ether.
After purification by re-precipitation, p- (N, N-dipropyl-sulfamido) -benzoic acid-cyclohexyl-aminoethyl ester is obtained.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE355140X | 1956-01-18 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH355140A true CH355140A (en) | 1961-06-30 |
Family
ID=20308756
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH355140D CH355140A (en) | 1956-01-18 | 1956-12-29 | Process for the preparation of sulfamidobenzoic acid esters |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH355140A (en) |
-
1956
- 1956-12-29 CH CH355140D patent/CH355140A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH426780A (en) | Process for the preparation of trifluoromethylphenylsulfonic acid trifluoromethylphenylamides | |
| CH355140A (en) | Process for the preparation of sulfamidobenzoic acid esters | |
| AT202143B (en) | Process for the preparation of new dimethylaminopropylidenexanthenes | |
| EP0271695B1 (en) | Process for preparing phosphinic or phosphonic-acid clorides | |
| CH616914A5 (en) | ||
| AT209906B (en) | Process for the preparation of new dicarbamates of aliphatic 1,3-diols | |
| DE753040C (en) | Process for the production of water-soluble acrylic acid and methacrylic acid derivatives | |
| AT203495B (en) | Process for the preparation of new tertiary amines | |
| AT274788B (en) | Process for the preparation of new N- (Hydroxycyclohexyl) -halogen-aminobenzylamines and their acid addition salts | |
| AT213390B (en) | Process for the preparation of α-monohalo-ω-lactams | |
| AT210438B (en) | Process for the production of new phosphonic or thiophosphonic acid esters | |
| DE480362C (en) | Process for the preparation of haloalkylarylcarboxylic acids which contain the halogen in the alkyl group | |
| DE907296C (en) | Process for the preparation of 1-phenyl-2,3-dimethylpyrazolone-4-carboxylic acid-diaethylaminoethyl ester | |
| AT73644B (en) | Process for the preparation of the esters of tertiary alcohols. | |
| AT228772B (en) | Process for the preparation of new basic substituted malononitriles | |
| AT212332B (en) | Process for the production of new thiophosphoric acid esters or thiophosphonic acid esters | |
| US3445514A (en) | 1,2,4,7,7 - pentachlorotricyclo(2,2,1,0,2,6)heptane-3-one-5-sulfonyl chloride | |
| AT218537B (en) | Process for the production of new phosphonic acid esters | |
| AT323123B (en) | PROCESS FOR THE PREPARATION OF N, N-DISUBSTITUTED CHARBONIC ACID AMIDES | |
| AT367394B (en) | METHOD FOR PRODUCING NEW INDANDERIVATES | |
| DE2242874A1 (en) | PROCESS FOR THE PREPARATION OF 1HYDROXY-2,4-DICHLORANTHRAQUINONE | |
| CH434283A (en) | Process for the preparation of substituted alkylamines | |
| CH298743A (en) | Process for the preparation of a heterocyclic carbamic acid derivative. | |
| CH436255A (en) | Process for the preparation of new substituted N- (phenylethyl) carbamic acid esters | |
| DE1203268B (en) | Process for the preparation of 2-chloro-3, 4-dimethyl-5-phenyl-1, 3, 2-oxazophospholidin-2-one |