CH223431A - Process for the preparation of an aminobenzoic acid ester of tocopherol. - Google Patents
Process for the preparation of an aminobenzoic acid ester of tocopherol.Info
- Publication number
- CH223431A CH223431A CH223431DA CH223431A CH 223431 A CH223431 A CH 223431A CH 223431D A CH223431D A CH 223431DA CH 223431 A CH223431 A CH 223431A
- Authority
- CH
- Switzerland
- Prior art keywords
- tocopherol
- preparation
- acid ester
- soluble
- aminobenzoic acid
- Prior art date
Links
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 title claims description 12
- 229930003799 tocopherol Natural products 0.000 title claims description 9
- 239000011732 tocopherol Substances 0.000 title claims description 9
- -1 aminobenzoic acid ester Chemical class 0.000 title claims description 7
- 229960001295 tocopherol Drugs 0.000 title claims description 7
- 235000010384 tocopherol Nutrition 0.000 title claims description 7
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 5
- 229960004050 aminobenzoic acid Drugs 0.000 title claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000011627 DL-alpha-tocopherol Substances 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 claims description 5
- 230000032050 esterification Effects 0.000 claims description 3
- 238000005886 esterification reaction Methods 0.000 claims description 3
- 239000000155 melt Substances 0.000 claims description 3
- 239000003208 petroleum Substances 0.000 claims description 3
- 239000011260 aqueous acid Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- OTLNPYWUJOZPPA-UHFFFAOYSA-N 4-nitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C=C1 OTLNPYWUJOZPPA-UHFFFAOYSA-N 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 150000005338 nitrobenzoic acids Chemical class 0.000 description 2
- 235000019149 tocopherols Nutrition 0.000 description 2
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 2
- 239000001707 (E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-ol Substances 0.000 description 1
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 1
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010021135 Hypovitaminosis Diseases 0.000 description 1
- BLUHKGOSFDHHGX-UHFFFAOYSA-N Phytol Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)C=CO BLUHKGOSFDHHGX-UHFFFAOYSA-N 0.000 description 1
- HNZBNQYXWOLKBA-UHFFFAOYSA-N Tetrahydrofarnesol Natural products CC(C)CCCC(C)CCCC(C)=CCO HNZBNQYXWOLKBA-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- BOTWFXYSPFMFNR-OALUTQOASA-N all-rac-phytol Natural products CC(C)CCC[C@H](C)CCC[C@H](C)CCCC(C)=CCO BOTWFXYSPFMFNR-OALUTQOASA-N 0.000 description 1
- 150000005415 aminobenzoic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- BOTWFXYSPFMFNR-PYDDKJGSSA-N phytol Chemical compound CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CO BOTWFXYSPFMFNR-PYDDKJGSSA-N 0.000 description 1
- 150000003839 salts Chemical group 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 208000030401 vitamin deficiency disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
- C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Darstellung eines Aminobenzoesäureesters des Tocopherols. Es hat bisher an geeigneten biologisch wirksamen, wohlkristallisierten Estern des Tocopherols gefehlt. Wie nun gefunden wurde, stellen die Nitro- und Aminobenzoe- säureester des Tocopherols leicht kristallisie rende Verbindungen dar.
Die Nitrobenzoe- säureester können dadurch gewonnen werden, dass man Tocopherole mit Nitrobenzoesäuren bezw. Derivaten derselben, wie z. B. Nitro- benzoylchlorid, verestert. Dran erhält die Aminoester zweckmässig durch Reaktion der entsprechenden Nitrobenzoesäureester. Die quartären Salze sind in Wasser löslich.
Statt reiner Tocopherole können Roh produkte, z. B. das rohe Kondensat von kern- alkylierten Hydrochinonen und Phytol bezw. -abkömmlingen, der Veresterung unterwor fen werden.
Die Verbindungen, welche gegebenenfalls auch zur Charakterisierung des Tocopherols gewonnen werden können, werden zur Her stellung oder als haltbare Präparate zur Be handlung der E-Avitaminose verwendet. Gegenstand des vorliegenden Patentes ist ein Verfahren zur Darstellung eines Amino- benzoesäureesters des Tocopherols, welches dadurch gekennzeichnet ist, dass man dl-a- Tocopherol mit p-1\Titrobenzoesäure verestert und den erhaltenen Ester reduziert.
plan kann auch rohes dl-a-Tocopherol der Ver- esterung unterwerfen.
Das p-Aminobenzoyl-dl-a-tocopherol ist ein weisses, kristallines Pulver, welches bei 141' schmilzt; es ist in Äther und Benzol, etwas weniger in Petroläther, löslich, in kaltem Äthanol und Methanol wenig und in wässerigen Säuren nicht löslich.
Das nach dem beanspruchten Verfahren hergestellte, bisher unbekannte p-Amino- benzoyl-dl-a-tocopherol soll als Arzneimittel verwendet werden.
Beispiel: Man erwärmt ein Gemisch von 5 Teilen dl-a-Tocopherol, 4 Teilen p-Nitrobenzoyl- chlorid und 20 Teilen Pyridin 1 Stunde im Dampfbad und entfernte dann das Pyridin unter 14 mm Druck.
Der Rückstand wird in Wasser aufgenommen, mit 50 Teilen Petrol- äther und mehrmals mit 10%iger Salzsäure extrahiert, um Pyridin und darauf mit 10 % iger Natriumcarbonatlösung die Nitro- benzoesäure zu entfernen. Nach dem Waschen mit Wasser, Trocknen mit Chlorealcium und Eindampfen bleibt ein dickes 01 zurück, welches erst nach zweitägigem Stehen im Exsikkator über Wachs allmählich fest wird.
Der Ester löst sich in warmem Athanol und Methanol und kristallisiert in der Kälte aus verdünnten Lösungen aus. Er schmilzt bei 41 .
Man hydriert die Lösung des Nitro- benzoesäureesters in Eisessig in Gegenwart von Palladiumkohle während 4 Stunden bis zum Aufhören der Wasserstoffaufnahme, putscht den Katalysator ab und wäscht mehrmals mit Wasser nach. Nun extrahiert man den Ester aus der trüben essigsauren Lösung mehrmals mit. Äther, giesst die Äther schicht durch die Palladiumkohle auf der Nutsche, die den Hauptteil des Esters zu- rückhält, wäscht die Ätherlösung darauf mehrmals mit Soda und Wasser und dampft ein.
Der feste Rückstand wird aus Methyl alkohol umkristallisiert.
Process for the preparation of an aminobenzoic acid ester of tocopherol. So far there has been a lack of suitable biologically active, well-crystallized esters of tocopherol. As has now been found, the nitro and aminobenzoic acid esters of tocopherol are easily crystallizing compounds.
The nitrobenzoic acid esters can be obtained by mixing tocopherols with nitrobenzoic acids. Derivatives of the same, such as B. nitrobenzoyl chloride, esterified. The amino ester is expediently obtained by reaction of the corresponding nitrobenzoic acid ester. The quaternary salts are soluble in water.
Instead of pure tocopherols, raw products such. B. the crude condensate of nuclear alkylated hydroquinones and phytol respectively. - derivatives that are subjected to esterification.
The compounds, which can optionally also be obtained for characterizing the tocopherol, are used for manufacture or as long-life preparations for treating E-avitaminosis. The subject of the present patent is a process for the preparation of an amino benzoic acid ester of tocopherol, which is characterized in that dl-a-tocopherol is esterified with p-1 \ titrobenzoic acid and the ester obtained is reduced.
plan can also subject crude dl-a-tocopherol to esterification.
The p-aminobenzoyl-dl-a-tocopherol is a white, crystalline powder which melts at 141 '; it is soluble in ether and benzene, a little less in petroleum ether, little soluble in cold ethanol and methanol, and not soluble in aqueous acids.
The previously unknown p-aminobenzoyl-dl-a-tocopherol produced by the claimed process is intended to be used as a medicament.
Example: A mixture of 5 parts of dl-a-tocopherol, 4 parts of p-nitrobenzoyl chloride and 20 parts of pyridine is heated in a steam bath for 1 hour and the pyridine is then removed under 14 mm pressure.
The residue is taken up in water and extracted with 50 parts of petroleum ether and several times with 10% strength hydrochloric acid in order to remove pyridine and then with 10% strength sodium carbonate solution the nitrobenzoic acid. After washing with water, drying with chlorealcium and evaporation, a thick oil remains, which only gradually solidifies over wax after standing in the desiccator for two days.
The ester dissolves in warm ethanol and methanol and crystallizes from dilute solutions in the cold. It melts at 41.
The solution of the nitrobenzoic acid ester is hydrogenated in glacial acetic acid in the presence of palladium carbon for 4 hours until the uptake of hydrogen ceases, the catalyst is washed off and washed several times with water. The ester is now extracted several times from the cloudy acetic acid solution. Ether, pours the ether layer through the palladium carbon on the suction filter, which holds back the main part of the ester, then washes the ether solution several times with soda and water and evaporates.
The solid residue is recrystallized from methyl alcohol.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH223431T | 1941-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH223431A true CH223431A (en) | 1942-09-15 |
Family
ID=4453015
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH223431D CH223431A (en) | 1941-05-15 | 1941-05-15 | Process for the preparation of an aminobenzoic acid ester of tocopherol. |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH223431A (en) |
-
1941
- 1941-05-15 CH CH223431D patent/CH223431A/en unknown
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