CH282384A - Process for the preparation of a nitrophenyl-oxazoline-carboxylic acid ester. - Google Patents
Process for the preparation of a nitrophenyl-oxazoline-carboxylic acid ester.Info
- Publication number
- CH282384A CH282384A CH282384DA CH282384A CH 282384 A CH282384 A CH 282384A CH 282384D A CH282384D A CH 282384DA CH 282384 A CH282384 A CH 282384A
- Authority
- CH
- Switzerland
- Prior art keywords
- threo
- oxazoline
- carboxylic acid
- nitro
- ethyl ester
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 4
- -1 nitrophenyl-oxazoline-carboxylic acid Chemical compound 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 5
- 238000002844 melting Methods 0.000 claims description 3
- 230000008018 melting Effects 0.000 claims description 3
- MOKJTKNJOFWLEF-UHFFFAOYSA-N 1-(2,3-dioxoaziridin-1-yl)oxyaziridine-2,3-dione Chemical compound C1(C(N1ON1C(C1=O)=O)=O)=O MOKJTKNJOFWLEF-UHFFFAOYSA-N 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- VHVGNTVUSQUXPS-JGVFFNPUSA-N (2s,3r)-2-amino-3-hydroxy-3-phenylpropanoic acid Chemical compound OC(=O)[C@@H](N)[C@H](O)C1=CC=CC=C1 VHVGNTVUSQUXPS-JGVFFNPUSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 230000000802 nitrating effect Effects 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- FBGCJSFUSFJRPC-UHFFFAOYSA-N 1-ethoxyaziridine-2,3-dione Chemical compound C(C)ON1C(C1=O)=O FBGCJSFUSFJRPC-UHFFFAOYSA-N 0.000 description 1
- WGMHMVLZFAJNOT-UHFFFAOYSA-N 1-ethoxyethylideneazanium;chloride Chemical compound [Cl-].CCOC(C)=[NH2+] WGMHMVLZFAJNOT-UHFFFAOYSA-N 0.000 description 1
- LBPFJHRFDJYOPK-UHFFFAOYSA-N 4-nitro-2-phenyl-4,5-dihydro-1,3-oxazole Chemical compound [O-][N+](=O)C1COC(C=2C=CC=CC=2)=N1 LBPFJHRFDJYOPK-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002918 oxazolines Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 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
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
Verfahren zur Herstellung eines Nitrophenyl-oxazolin-carhonsäureesters. Die Erfindung betrifft ein Verfahren zur Herstellung von DL-threo-2-Methyl-5-(p-nitro- phenyl) -4-carbäthoxy-oxazolin.
Es wurde gefunden, dass die genannte Ver bindung erhalten werden kann, indem man erfindungsgemäss DL-threo-ss-Phenyl-serin- äthylester diacetyliert, vorzugsweise mit Acet- anhydrid oder Acetylchlorid, ,das erhaltene Acylierungsprodukt nitriert und anschliessend zum DL-threo-ss-(p-Nitro-phenyl)-serin hydro- lysiert,
in letzterem die Carboxylgruppe in die Carbäthoxygruppe überführt und den gebil deten DL-threo-ss-(p-Nitro-phenyl)-serinäthyl- ester mit einem Acetimidoäther zum entspre chenden DL-threo-2-Methyl-5-(p-nitro-phe- nyl)-oxazolin-4-carbonsäureäthylester umsetzt.
Das neue Oxazolinderiv at ist eine unter vermindertem Druck destillierbare Verbin dung, welche in den gebräuchlichen organi schen Lösungsmitteln, nicht dagegen in Was ser, löslich ist. Aus Alkohol sind Kristalle vom Schmelzpunkt 91 bis 92 C erhältlich. Die neue Verbindung kann durch selektive Reduktion der Carbonestergruppe in den entsprechenden Nitrophenyl-oxazolinalkohol übergeführt wer den und ist daher ein geeignetes Ausgangs material für die Synthese von Chlorampheni- col und ähnlichen Verbindungen. Sie soll als Zwischenprodukt Verwendung finden.
<I>Beispiel:</I> 200 Gewichtsteile DL-threo-ss-Phen@#1-serin- äthylester werden mit 250 Volumteilen Acet- anhydrid übergossen und unter Eiskühlung mit 170 Volumteilen Pyridin versetzt. Man lässt diese Mischung 20 Stunden bei Zimmer temperatur stehen, erwärmt anschliessend noch 2 Stunden auf dem Dampfbad und dampft dann unter vermindertem Drucke (12 mm Hg) vollständig ein.
Der feste Rückstand wird in Alkohol gelöst und der diacetylierte DL- threo-ss-Phenyl-serin-äthylester durch Zugabe von Wasser ausgefällt. Ausbeute 229 Ge wichtsteile. Schmelzpunkt 170 bis 171 C.
25 Gewichtsteile des diacetylierten DL- threo-ss-Phenyl-serin-äthylesters werden inner halb 5 bis 7 Minuten in 100 Volumteile rau chende Salpetersäure von -20 C so einge tragen, dass die Temperatur 6 bis 8 C nicht übersteigt. Nun wird das Gemisch sofort auf Eis gegossen und dreimal mit je 200 Volum- teilen Essigester ausgezogen. Die Essigester lösung wird mit Natriumbicarbonatlösung und dann mit Wasser neutral gewaschen und über Natriumsulfat getrocknet.
Beim Einengen der Essigesterlösung auf etwa 100 Volumteile und Versetzen mit Petroläther scheiden sich 21,5 Gewichtsteile des diacetylierten DL-threo-ss- (p-Nitro-phenyl)-serin-äthylest.ers ab, welcher nach Umkristallisieren aus Essigester-Petrol- äther bei 122 bis 124 C schmilzt.
80 Gewichtsteile des diacetylierten DL threo-ss-(p-Nitro-phenyl)-serinäthylesters wer den mit. 500 Volumteilen 10 o/oiger Salzsäure während 21/.. Stunden auf dem Dampfbad erwärmt, wobei eine klare Lösung entsteht. Diese wird, nachdem abgekühlt, mit 100 Vo- lumteilen Essigester ausgeschüttelt. Die wäs- serige Lösung wird im Vakuum vollständig eingedampft, zum Schluss mehrmals unter Zugabe von absolutem Alkohol.
Der Rück stand wird in 1200 Volumteilen absolutem Alkohol suspendiert, und nun leitet man Salz säuregas ein, bis die Lösung zu sieden an fängt. Die Mischung wird mit Eis gekühlt und das Einleiten des Salzsäuregases bis zur Sättigung fortgesetzt. Nach 20stündigem Ste hen im Kühlschrank dampft man den Alkohol im Vakuum vollständig ab, löst in wenig Al kohol und versetzt mit Äther. Nach mehrstün digem Stehen in der Kälte scheiden sich 46 Gewichtsteile DL-threo-ss-(p-Nitro-phenyl)- serinäthy lester-hydrochlorid ab.
Aus Alkohol- Äther umkristallisiert schmilzt dieses Hydro- chlorid bei 161 bis 163 C.
25 Gewichtsteile DL-threo-ss-(p-Nitro-phe- nyl)-serin-äthylester-hydrochlorid werden in 50 Volumteilen Wasser gelöst. Daneben wer den 17 Gewichtsteile Acetimidoäthyläther- hydrochlorid in 500 Volumteilen Äther suspen diert und mit einer kalt gesättigten und auf 0 C gekühlten wässerigen Lösung von 22 Ge wichtsteilen Kaliumcarbonat versetzt und während etwa 5 Minuten gut durchgeschüt telt.
Nun trennt. man die Ätherlösung, welche den freien Acetimidoäthyläther enthält, ab und giesst sie zu der wässerigen Lösung des DL-threo-ss-(p-1Vitro-phenyl)-serin-äthylester- hydrochlorids. Dieses Gemisch wird während 20 Stunden bei Zimmertemperatur kräftig durchgerührt; darauf trennt man die Äther schicht ab, wäscht sie mit verdünnter Natrium bicarbonatlösung und Wasser und trocknet sie über Natriumsulfat.
Nach Abdampfen des Äthers bleiben 15,5 Gewiehtsteile eines vis kosen Öls zurück, welches im Hochvakuum (0,05 mm Hg) bei 155 bis 162 C destilliert und das DL-threo-\'-llethvl-4-earbäthoxy-5-(p- nitro-phenyl) -oxazolin darstellt. Es kann durch mehrtägiges Stehenlassen einer gesät tigten alkoholischen Lösung kristallisiert wer den; die Kristalle schmelzen bei 91 bis 920 C.
Process for the preparation of a nitrophenyl-oxazoline-carboxylic acid ester. The invention relates to a process for the preparation of DL-threo-2-methyl-5- (p-nitro-phenyl) -4-carbethoxy-oxazoline.
It has been found that the compound mentioned can be obtained by diacetylating DL-threo-ss-phenyl-serine ethyl ester, preferably with acetic anhydride or acetyl chloride, nitrating the acylation product obtained, and then nitrating to DL-threo-ss - (p-Nitro-phenyl) -serine hydrolyzed,
in the latter, the carboxyl group is converted into the carbethoxy group and the formed DL-threo-ss- (p-nitro-phenyl) -serine ethyl ester with an acetimido ether to form the corresponding DL-threo-2-methyl-5- (p-nitro- phenyl) -oxazoline-4-carboxylic acid ethyl ester.
The new oxazoline derivative is a compound which can be distilled under reduced pressure and which is soluble in common organic solvents, but not in water. Crystals with a melting point of 91 to 92 ° C are available from alcohol. The new compound can be converted into the corresponding nitrophenyl-oxazoline alcohol by selective reduction of the carbon ester group and is therefore a suitable starting material for the synthesis of chloramphenicol and similar compounds. It should be used as an intermediate product.
<I> Example: </I> 200 parts by weight of DL-threo-ss-phen @ # 1-serine ethyl ester are poured over with 250 parts by volume of acetic anhydride and, while cooling with ice, 170 parts by volume of pyridine are added. This mixture is left to stand for 20 hours at room temperature, then heated for a further 2 hours on the steam bath and then completely evaporated under reduced pressure (12 mm Hg).
The solid residue is dissolved in alcohol and the diacetylated DL-threo-ss-phenyl-serine ethyl ester is precipitated by adding water. Yield 229 parts by weight. Melting point 170 to 171 C.
25 parts by weight of the diacetylated DL-threo-ss-phenyl-serine-ethyl ester are carried within 5 to 7 minutes in 100 parts by volume of fuming nitric acid at -20 C so that the temperature does not exceed 6 to 8 C. The mixture is then immediately poured onto ice and extracted three times with 200 parts by volume of ethyl acetate each time. The ethyl acetate solution is washed neutral with sodium bicarbonate solution and then with water and dried over sodium sulfate.
When the ethyl acetate solution is concentrated to about 100 parts by volume and petroleum ether is added, 21.5 parts by weight of the diacetylated DL-threo-ss- (p-nitro-phenyl) -serine-äthylest.ers separate, which after recrystallization from ethyl acetate-petroleum ether melts at 122 to 124 C.
80 parts by weight of the diacetylated DL threo-ss- (p-nitro-phenyl) -serine ethyl ester who with. 500 parts by volume of 10% hydrochloric acid heated on the steam bath for 21 / .. hours, a clear solution being formed. After cooling, this is shaken out with 100 parts by volume of ethyl acetate. The aqueous solution is completely evaporated in vacuo, finally several times with the addition of absolute alcohol.
The residue is suspended in 1200 parts by volume of absolute alcohol, and hydrochloric acid gas is now passed in until the solution begins to boil. The mixture is cooled with ice and the introduction of the hydrochloric acid gas is continued until it is saturated. After standing in the refrigerator for 20 hours, the alcohol is completely evaporated in vacuo, dissolved in a little alcohol and ether is added. After standing in the cold for several hours, 46 parts by weight of DL-threo-ss- (p-nitro-phenyl) - serinäthy lester hydrochloride separate.
Recrystallized from alcohol-ether, this hydrochloride melts at 161 to 163 C.
25 parts by weight of DL-threo-ss- (p-nitro-phenyl) serine ethyl ester hydrochloride are dissolved in 50 parts by volume of water. In addition, who suspend the 17 parts by weight of acetimidoethyl ether hydrochloride in 500 parts by volume of ether and mixed with a cold saturated and cooled to 0 C aqueous solution of 22 parts by weight of potassium carbonate and shaken well for about 5 minutes.
Well separates. the ether solution, which contains the free acetimido ethyl ether, is poured off and it is poured into the aqueous solution of DL-threo-ss- (p-1-nitro-phenyl) -serine-ethyl ester hydrochloride. This mixture is vigorously stirred for 20 hours at room temperature; the ether layer is then separated off, washed with dilute sodium bicarbonate solution and water and dried over sodium sulfate.
After evaporation of the ether, 15.5 parts by weight of a viscous oil remain, which distills in a high vacuum (0.05 mm Hg) at 155 to 162 C and the DL-threo - \ '- llethvl-4-earbethoxy-5- (p - Nitro-phenyl) -oxazoline represents. It can be crystallized by leaving a saturated alcoholic solution to stand for several days; the crystals melt at 91 to 920 C.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH282384T | 1950-03-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH282384A true CH282384A (en) | 1952-04-30 |
Family
ID=4483645
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH282384D CH282384A (en) | 1950-03-27 | 1950-03-27 | Process for the preparation of a nitrophenyl-oxazoline-carboxylic acid ester. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH282384A (en) |
-
1950
- 1950-03-27 CH CH282384D patent/CH282384A/en unknown
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