CH213149A - Process for the preparation of d, l-a-tocopherol. - Google Patents
Process for the preparation of d, l-a-tocopherol.Info
- Publication number
- CH213149A CH213149A CH213149DA CH213149A CH 213149 A CH213149 A CH 213149A CH 213149D A CH213149D A CH 213149DA CH 213149 A CH213149 A CH 213149A
- Authority
- CH
- Switzerland
- Prior art keywords
- preparation
- tocopherol
- condensation
- petroleum ether
- vol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title claims description 5
- AUFZRCJENRSRLY-UHFFFAOYSA-N 2,3,5-trimethylhydroquinone Chemical compound CC1=CC(O)=C(C)C(C)=C1O AUFZRCJENRSRLY-UHFFFAOYSA-N 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000007859 condensation product Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- -1 allyl halides Chemical class 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L calcium carbonate Substances [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- SUNVJLYYDZCIIK-UHFFFAOYSA-N durohydroquinone Chemical compound CC1=C(C)C(O)=C(C)C(C)=C1O SUNVJLYYDZCIIK-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 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)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Darstellung von d,1-a-Tocopherol. Es ist bekannt, dass man alkylierte 2-Di- alkyl-6-oxychromane darstellen kann durch Kondensation von ss-Dialkylallylalkoholen respektive -allylhalogeniden mit alkylierten Hydrochinonen, die mindestens ein Wasser stoffatom im Benzalkern tragen (siehe z. B.
1 Ielvetica Chimica Acta Bd. 21, 1938, S. 520; Nature Bd. 142, 1938, S. 36: Helvetica Chi- mica Acta. Bd. 22, 1939, S. 337).
Es wurde nun gefunden, dass Dialkyl- äthinylcarbinole und alkylierte Hydrochi- none mit mindestens einer unbesetzten Stelle im Kern durch saure Kondensationsmittel zu bicyclischen Kondensationsprodukten., 2-Di- alkyl-6-oxychromenen-(3,4), vereinigt wer den.
Diese Kondensationsprodukte nehmen in Gegenwart eines geeigneten Katalysators, wie Palladiumkohle, Palladium-calciumca.r- bonat oder Platinoxyd, leicht 1 Mol. Wasser stoff auf. Die hydrierten Produkte stimmen in ihren Eigenschaften mit den 2-Dialkyl-6- oxychromanen überein. Sie sollen als Arznei mittel verwendet werden.
Die Umsetzung verläuft nach folgendem Schema:
EMI0001.0035
R, bedeutet Wasserstoff oder Alkvl. R' be deutet Alkyl.
Durch die bisher unbekannte Konden sation von 1)ialkyläthinylcarbinolen mit alkylierten Hydrochinonen, welche minde stens 1 Wasserstoffatom im Benzolkern tra gen. wird eine neue Körperklasse. nämlich die 2-Dialkyl-6-oxychromene-(3,4) präpara- tiv leicht zugänglich. Die Hydrierung dieser Kondensationsprodukte stellt ein neues Ver fahren zur Darstellung von 6-Oxychroma- nen dar.
Gegenstand des vorliegenden Patentes ist ein Verfahren zur Darstellung von d,l-a- Tocopherol, welches dadurch gekennzeichnet ist, dass man Trimethylhydrochinon in Ge genwart von sauren Kondensationsmitteln auf ?.6.10- Trimethyl -14-äthinyl - pentade- canol-(14) einwirken lässt und das ent stehende 2,5,7,8-Tetramethyl-2-(4',8',12'-tri- methyl - tridecyl) -6 - oxychromen- (1,2) hy driert.
<I>Beispiel:</I> 3 Teile Trimethylhydrochinon, 2 Teile wasserfreies Zinkchlorid und 10 Teile De- calin werden unter Rühren und unter Einlei ten von Kohlensäure auf 150 erhitzt. Man tropft 6 Teile 2,6,10-Trimethyl-14-äthinyl- pentadecanol-(14) (dargestellt nach Fischer und Löwenberg. Annalen der Chemie Bd. 475, 1929. S. 195) zu und rührt darauf 2 Stunden bei 150 .
Nach dem Erkalten fügt man Was ser und Petroläther vom Siedepunkt 50-70 zu, wäscht die Petrolätherlösung mit 1-n Na tronlauge, 1-n Salzsäure und Mrasser und trocknet mit Natriumsulfat. Darauf adsor- biert man die Lösung an eine Aluminium oxydsäule und entwickelt das Chromato- gramm mit viel Petroläther. An der Säule entstehen 3 Zonen: eine schmale. braune Oberschicht. eine graue Hauptzone und ein gelber Ring.
Man eluiert die graue Haupt- zone mit einer Mischung von Methylalkohol und Äther (3 : 1) und verdampft das Lö sungsmittel. Der Extrakt ist ein sehr oxy dationsempfindliches, bräunliches 01, welches neutrale methylalkoholische Silh(,rnitratlö- sung reduziert und bei der thermischen Zer setzung ein Sublimat von Durohydrochinon abspaltet.
Dieser Extrakt der grauen Hauptzone wird in der 10fachen Menge Essigester gelöst und in Gegenwart von Palladiumkohle-Kata- lysator bei Raumtemperatur ohne Anwen dung von Druck mit Wasserstoff geschüttelt, wob(@i 1 11o1 Wasserstoff aufgenommen wird. Dlirauf wird der Katalysator abfil- triert, der Essigester verdampft, das hy drierte Kondensationsprodukt in Petroläther vom Siedepunkt 50-70 gelöst und zur Reinigung durch eine kleine Magnesiumsul- fatsäule filtriert.
Man adsorbiert das Filtrat nun an eine Aluminiumoxydsäule und ent wickelt das Chromatogramm mit viel Petrol- äther vom Siedepunkt 50-70 . Die fast farblose Hauptzone im obersten Teil der Säule wird mit einer Mischung von Methyl alkohol und Äther (3 : 1) eluiert und das Lösungsmittel verdampft. Der Extrakt ist ein gelbliches 01, n 2 = 1,506, das iden tisch ist mit dem d,1-a-Toaopherol (Helvetica Chimica Acta Bd. 21, 1938.
S. 520). 5 mg der Verbindung sind an der Vitamin-E-frei ernährten Ratte biologisch wirksam.
Process for the preparation of d, 1-a-tocopherol. It is known that alkylated 2-dialkyl-6-oxychromanes can be prepared by condensation of ß-dialkylallyl alcohols or allyl halides with alkylated hydroquinones which have at least one hydrogen atom in the benzal nucleus (see, for example,
1 Ielvetica Chimica Acta Vol. 21, 1938, p. 520; Nature Vol. 142, 1938, p. 36: Helvetica Chimica Acta. Vol. 22, 1939, p. 337).
It has now been found that dialkylethinylcarbinols and alkylated hydroquinones with at least one vacant position in the core are combined by acidic condensation agents to form bicyclic condensation products, 2-dialkyl-6-oxychromenes- (3,4).
In the presence of a suitable catalyst, such as palladium-carbon, palladium-calcium carbonate or platinum oxide, these condensation products easily absorb 1 mol of hydrogen. The hydrogenated products have the same properties as the 2-dialkyl-6-oxychromanes. They are intended to be used as medicinal products.
The implementation proceeds according to the following scheme:
EMI0001.0035
R means hydrogen or Alkvl. R 'is alkyl.
The previously unknown condensation of 1) alkylethinyl carbinols with alkylated hydroquinones, which carry at least 1 hydrogen atom in the benzene nucleus, creates a new body class. namely the 2-dialkyl-6-oxychromene- (3,4) easily accessible preparatively. The hydrogenation of these condensation products represents a new process for the preparation of 6-oxychromans.
The subject of the present patent is a process for the preparation of d, la-tocopherol, which is characterized in that trimethylhydroquinone is allowed to act on 6.10-trimethyl-14-äthinyl-pentadecanol- (14) in the presence of acidic condensing agents and the resulting 2,5,7,8-tetramethyl-2- (4 ', 8', 12'-trimethyl-tridecyl) -6-oxychromen- (1,2) hydrogenated.
<I> Example: </I> 3 parts of trimethylhydroquinone, 2 parts of anhydrous zinc chloride and 10 parts of decalin are heated to 150 while stirring and introducing carbonic acid. 6 parts of 2,6,10-trimethyl-14-äthinyl-pentadecanol- (14) (prepared according to Fischer and Löwenberg. Annalen der Chemie, Vol. 475, 1929, p. 195) are added dropwise and the mixture is then stirred at 150 for 2 hours.
After cooling, what water and petroleum ether with a boiling point of 50-70 are added, the petroleum ether solution is washed with 1N sodium hydroxide solution, 1N hydrochloric acid and water and dried with sodium sulfate. The solution is then adsorbed on an aluminum oxide column and the chromatogram is developed with a lot of petroleum ether. There are 3 zones on the column: a narrow one. brown upper class. a gray main zone and a yellow ring.
The main gray zone is eluted with a mixture of methyl alcohol and ether (3: 1) and the solvent is evaporated. The extract is a very oxidation-sensitive, brownish oil, which reduces neutral methyl alcoholic nitrate solution and splits off a sublimate of durohydroquinone during thermal decomposition.
This extract from the gray main zone is dissolved in 10 times the amount of ethyl acetate and shaken with hydrogen in the presence of a palladium-carbon catalyst at room temperature without the use of pressure, whereby (@ 1 11o1 hydrogen is taken up. The catalyst is then filtered off, the ethyl acetate evaporates, the hydrogenated condensation product dissolved in petroleum ether with a boiling point of 50-70 and filtered through a small magnesium sulphate column for purification.
The filtrate is then adsorbed on an aluminum oxide column and the chromatogram is developed with a lot of petroleum ether with a boiling point of 50-70. The almost colorless main zone in the uppermost part of the column is eluted with a mixture of methyl alcohol and ether (3: 1) and the solvent is evaporated. The extract is a yellowish 01, n 2 = 1.506, which is identical to the d, 1-a-toaopherol (Helvetica Chimica Acta Vol. 21, 1938.
P. 520). 5 mg of the compound are biologically active on the rat fed without vitamin E.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH213149T | 1939-07-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH213149A true CH213149A (en) | 1941-01-15 |
Family
ID=4448109
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH213149D CH213149A (en) | 1939-07-28 | 1939-07-28 | Process for the preparation of d, l-a-tocopherol. |
| CH221846D CH221846A (en) | 1939-07-28 | 1940-06-10 | Process for the preparation of d, l- tocopherol. |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH221846D CH221846A (en) | 1939-07-28 | 1940-06-10 | Process for the preparation of d, l- tocopherol. |
Country Status (1)
| Country | Link |
|---|---|
| CH (2) | CH213149A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4716238A (en) * | 1983-02-15 | 1987-12-29 | Alkaloida Vegyeszeti Gyar | Chromene derivatives useful as insecticides |
| US4866089A (en) * | 1983-02-16 | 1989-09-12 | Alkaloida Vegyeszeti Gyar | Chromene derivatives and pesticidal composition comprising the same |
-
1939
- 1939-07-28 CH CH213149D patent/CH213149A/en unknown
-
1940
- 1940-06-10 CH CH221846D patent/CH221846A/en unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4716238A (en) * | 1983-02-15 | 1987-12-29 | Alkaloida Vegyeszeti Gyar | Chromene derivatives useful as insecticides |
| US4866089A (en) * | 1983-02-16 | 1989-09-12 | Alkaloida Vegyeszeti Gyar | Chromene derivatives and pesticidal composition comprising the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CH221846A (en) | 1942-06-15 |
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