DE1068702B - Process for the production of vitamin A and its biologically active derivatives - Google Patents
Process for the production of vitamin A and its biologically active derivativesInfo
- Publication number
- DE1068702B DE1068702B DENDAT1068702D DE1068702DB DE1068702B DE 1068702 B DE1068702 B DE 1068702B DE NDAT1068702 D DENDAT1068702 D DE NDAT1068702D DE 1068702D B DE1068702D B DE 1068702DB DE 1068702 B DE1068702 B DE 1068702B
- Authority
- DE
- Germany
- Prior art keywords
- parts
- group
- vitamin
- proton
- production
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 8
- 229940045997 Vitamin A Drugs 0.000 title description 4
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 title description 4
- 229960003471 retinol Drugs 0.000 title description 4
- 235000019155 vitamin A Nutrition 0.000 title description 4
- 239000011719 vitamin A Substances 0.000 title description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 3
- -1 vinyl- Chemical group 0.000 claims description 6
- 239000011782 vitamin Substances 0.000 claims description 6
- 229940088594 Vitamin Drugs 0.000 claims description 5
- 239000000370 acceptor Substances 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
- 235000013343 vitamin Nutrition 0.000 claims description 5
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 5
- 229930003231 vitamins Natural products 0.000 claims description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 150000004679 hydroxides Chemical class 0.000 claims description 2
- 150000007522 mineralic acids Chemical group 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000005712 crystallization Effects 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N Triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N Butanol Natural products CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- PZGYHDPZANRCSM-PKNBQFBNSA-N (1E)-3-methyl-1-(2,6,6-trimethylcyclohexen-1-yl)penta-1,4-dien-3-ol Chemical compound CC1=C(\C=C\C(C)(O)C=C)C(C)(C)CCC1 PZGYHDPZANRCSM-PKNBQFBNSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZPDIRKNRUWXYLJ-UHFFFAOYSA-N 2,2-dimethyloxolane Chemical compound CC1(C)CCCO1 ZPDIRKNRUWXYLJ-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N Benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N Carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- WJTCGQSWYFHTAC-UHFFFAOYSA-N Cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N Retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 229960004319 Trichloroacetic Acid Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N Trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 239000004914 cyclooctane Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N iso-propanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N n-methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L na2so4 Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000001264 neutralization Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N o-xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002926 oxygen Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propanol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229960000342 retinol acetate Drugs 0.000 description 1
- 235000019173 retinyl acetate Nutrition 0.000 description 1
- 239000011770 retinyl acetate Substances 0.000 description 1
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000526 short-path distillation Methods 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Inorganic materials [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing Effects 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C403/00—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone
- C07C403/20—Derivatives of cyclohexane or of a cyclohexene or of cyclohexadiene, having a side-chain containing an acyclic unsaturated part of at least four carbon atoms, this part being directly attached to the cyclohexane or cyclohexene or cyclohexadiene rings, e.g. vitamin A, beta-carotene, beta-ionone having side-chains substituted by carboxyl groups or halides, anhydrides, or (thio)esters thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/16—Systems containing only non-condensed rings with a six-membered ring the ring being unsaturated
Description
BUNDESREPUBLIK DEUTSCHLANDFEDERAL REPUBLIC OF GERMANY
DEUTSCHESGERMAN
INTEHNAT. KL. C 07 CINTEHNAT. KL. C 07 C
PATENTAMTPATENT OFFICE
AUSLEGESCHRIFT 1068 702EXPLORATION PAPER 1068 702
B 48189 IVb/12 oB 48189 IVb / 12 o
ANMELDETAG: 14.MÄRZ1958REGISTRATION DATE: MARCH 14, 1958
BEKANNTMACHUNG
DER ANMELDUNG
UND AUSGABE DEK
AUSLEGESCHRIFT: 12. NOVEMBER 1959NOTICE
THE REGISTRATION
AND ISSUE DEK
EDITORIAL: NOVEMBER 12, 1959
Gegenstand der nicht veröffentlichten Patentanmeldung B 45902 IVb/12 ο ist ein Verfahren zur Herstellung von Vitamin A und seinen biologisch wirksamen Derivaten, bei dem 5-[2',6',6'-Trimethylcyclohexen-(l')-yl-(l')]-3-methyl-3-hydroxy-pentadien-(l ,4) (Vinyl-/?-ionol) gemeinsam mit Triarylphosphinhydrohalogeniden und einem ungesättigten Aldehyd der allgemeinen FormelThe subject of the unpublished patent application B 45902 IVb / 12 o is a method for production of vitamin A and its biologically active derivatives, in which 5- [2 ', 6', 6'-trimethylcyclohexen- (l ') - yl- (l')] - 3-methyl-3-hydroxypentadiene- (l , 4) (vinyl - /? - ionol) together with triarylphosphine hydrohalides and an unsaturated aldehyde of the general formula
OHC-C = CH-ROHC-C = CH-R
CH3 CH 3
in der R eine CH2OH-Gruppe, eine veresterte CH2OH-Gruppe, eine verätherte CH2OH-Gruppe, eine COOH-Grappe, eine veresterte COOH-Gruppe oder eine CH3-Gruppe bedeutet, in Gegenwart von säurebindenden Mitteln umgesetzt wird. Dieses Verfahren erfordert die gesonderteHerstellungderTriarylphosphinhydrohalogenide. Es wurde nun gefunden, daß man dieses Verfahren wirtschaftlicher und einfacher gestalten kann, wenn man Vinyl-j8-ionol mit Triarylphosphinen in Anwesenheit von Protonendonatoren und einem Aldehyd der allgemeinen Formelin which R is a CH 2 OH group, an esterified CH 2 OH group, an etherified CH 2 OH group, a COOH group, an esterified COOH group or a CH 3 group, reacted in the presence of acid-binding agents will. This process requires the separate preparation of the triarylphosphine hydrohalides. It has now been found that this process can be made more economical and simpler if vinyl-j8-ionol is used with triarylphosphines in the presence of proton donors and an aldehyde of the general formula
OHC-C = CH-ROHC-C = CH-R
CH3 CH 3
in der R die oben angegebene Bedeutunghat, mittels eines Protonenakzeptors als säurebindendem Mittel umsetzt. Als Protonendonatoren eignen sich anorganische Säuren, vornehmlich die Halogenwasserstoffsäuren und Sauerstoffsäuren des Schwefels. Darüber hinaus sind alle solche Säuren geeignet, die mit Triarylphosphinen Salze vom Typin which R has the meaning given above, by means of a proton acceptor as an acid-binding agent. Inorganic acids are suitable as proton donors, especially the hydrohalic acids and Oxygen Acids of Sulfur. In addition, all acids are suitable which salts with triarylphosphines of type
bilden. R steht für gleiche oder verschiedene aromatische Reste. X<-) steht für den Rest einer anorganischen oder starken organischen Säure, z. B. Trichloressigsäure oder Benzolsulfonsäure.form. R stands for identical or different aromatic radicals. X <-) stands for the remainder of an inorganic or strong organic acid, e.g. B. trichloroacetic acid or benzenesulfonic acid.
Die Ausführung der neuen Verfahrensweise gestaltet sich außerordentlich einfach, man kann z. B. zu einer Verfahren zur HerstellungThe execution of the new procedure is extremely simple; B. to one Method of manufacture
von Vitamin A und seinen biologisch.of vitamin A and its biological.
wirksamen Derivateneffective derivatives
Anmelder:Applicant:
Badische Anilin- & Soda-FabrikAniline & Soda Factory in Baden
Aktiengesellschaft,Corporation,
Ludwigshafen/RheinLudwigshafen / Rhine
Dr. Horst Pommer und Dr. Wilhelm Sarnecki,Dr. Horst Pommer and Dr. Wilhelm Sarnecki,
Ludwigshafen/Rhein,
sind als Erfinder genannt wordenLudwigshafen / Rhine,
have been named as inventors
Lösung oder Suspension von Vinyl-/?-ionol und einem Triarylphosphin die vorgenannten Protonendonatoren je nach Aggregatzustand eingasen, eintropfen oder durch einen Pulvertrichter zumischen und die weiteren Umsetzungen analog, wie in der Patentanmeldung B 45902Solution or suspension of vinyl - /? - ionol and a triarylphosphine the aforementioned proton donors Depending on the state of aggregation, gas in, drip in or mix in through a powder funnel and the other reactions analogous to that in patent application B 45902
as IVb/12 ο beschrieben, vornehmen. Ebenso ist es möglich, die Protonendonatoren z. B. in einem Lösungsmittel vorzu~ legen und die Reaktionskomponenten dann hinzuzufügen. Daß diese Maßnahmen zu den gewünschten Verbindungen der Vitamin Α-Reihe führen, ist besonders über-as IVb / 12 ο described. It is also possible the proton donors e.g. B. in a solvent and then add the reaction components. It is particularly clear that these measures lead to the desired compounds of the vitamin Α series.
raschend, wenn man berücksichtigt, daß das Vinyl-/?-ionol gegen Säuren, insbesondere Halogenwasserstoffsäuren, außerordentlich empfindlich ist und fast spontan unter Wasserabspaltung in die Retroverbindung 5-[(2',6',6'~Tri~ methylcyclohexen - (2') - yliden - (1')] - 3 - methylpentadien-surprising when you consider that the vinyl - /? - ionol to acids, especially hydrohalic acids, is extremely sensitive and almost spontaneously under Elimination of water into the retro compound 5 - [(2 ', 6', 6 '~ Tri ~ methylcyclohexen - (2 ') - ylidene - (1')] - 3 - methylpentadiene
(1,3) übergeht (vergleiche z. B. H. O. Huisman und Mitarbeiter, Rec. Trav. chim. des Pays-Bas, Bd. 71, 1952, S. 911). Der Reaktionsablauf selber ist, wie eingehende Untersuchungen vermuten lassen, außerordentlich verwickelt. (1,3) passes over (compare e.g. H. O. Huisman and coworkers, Rec. Trav. Chim. Des Pays-Bas, Vol. 71, 1952, P. 911). As detailed investigations suggest, the course of the reaction itself is extraordinarily complicated.
Für die Synthese von Vitamin A-acetat (IV) aus VinyljS-ionol (I), Triphenylphosphin (II), Chlorwasserstoff als Protonendonator, y-Acetoxy-a-methylcrotonaldehyd (III) und Natriumhydroxyd als Protonenakzeptoren läßt sich das Verfahren wie folgt formulieren:For the synthesis of vitamin A acetate (IV) from vinyljS-ionol (I), triphenylphosphine (II), hydrogen chloride as proton donor, y-acetoxy-a-methylcrotonaldehyde (III) and sodium hydroxide as proton acceptors, the process can be formulated as follows:
H-Cxc/ H - C x c /
H2C CH 2 CC
ι
= CH-C-CH = CH, ι
= CH-C-CH = CH,
H2CH 2 C
CH3 CH 3
(I)(I)
CH9 CH 9
CH3 CH 3
+ (CeHB)3P (II)+ (C e H B ) 3 P (II)
+ HCl+ HCl
+ OHc-C = CH-CH2-OCOCH3 (III)+ OHc-C = CH-CH 2 -OCOCH 3 (III)
NaOH CH,NaOH CH,
909' 648^909 '648 ^
CHa CH a
(IV)(IV)
+ (C6Hg)3PO
-+- NaCl
+ 2H9O+ (C 6 Hg) 3 PO
- + - NaCl
+ 2H 9 O
Für das Λ'erfahren geeignete Lösungs- bzw. Dispergiermittel sind z. B. Äther, wie Diäthyläther, Tetrahydrofuran, Dimethyltetrahydrofuran, Dioxan, Kohlenwasserstoffe, wie Benzol, Toluol, Xylol, Cyclohexan, Cyclooctan, Isooctan, Alkohole, wie Methanol, Äthanol, Isopropanol, Propanol, die Butanole und Benzylalkohol sowie Dimethylformamid und N-Methylpyrrolidon. Die Lösungsmittel müssen nicht notwendigerweise wasserfrei sein.Suitable solvents or dispersants for the process are z. B. ethers, such as diethyl ether, tetrahydrofuran, dimethyltetrahydrofuran, dioxane, hydrocarbons, such as benzene, toluene, xylene, cyclohexane, cyclooctane, isooctane, alcohols such as methanol, ethanol, isopropanol, Propanol, the butanols and benzyl alcohol as well as dimethylformamide and N-methylpyrrolidone. the Solvents do not necessarily have to be anhydrous.
Die Reaktionstemperatur kann in weilen Grenzen, etwa von —50 bis -f 1000C, geändert werden; vorteilhaft sind Temperaturen um O0C. Die Ausgangsstoffe verwendet man im allgemeinen in äquimolekularen Mengen. Die Menge an säurebindenden Mitteln kann je nach Wahl der Aldehydkomponente, z.B. wenn R = COOH ist, ein Mehrfaches der theoretisch erforderlichen sein; ein Überschuß ist oft sogar von λτ orteil.The reaction temperature can in bore limits, for instance from -50 to 100 0 -f C, to be changed; Temperatures around 0 ° C. are advantageous. The starting materials are generally used in equimolecular amounts. The amount of acid-binding agents can, depending on the choice of the aldehyde component, for example when R = COOH, be a multiple of what is theoretically required; an excess is often even advantageous for λ τ.
Als Protonenakzeptoren eignen sich säurebindende Mittel, wie Alkali- und Erdalkalialkoholate, Alkali- und Erdalkalihydroxyde, Alkali- und Erdalkaliami de, Alkali- und Erdalkalienolate von Ketonen, Ammoniak und stark basische Amine.Suitable proton acceptors are acid-binding agents, such as alkali and alkaline earth alcoholates, alkali and Alkaline earth hydroxides, alkali and alkaline earth, alkali and alkaline earth enolates of ketones, ammonia and strong basic amines.
Das Verfahren macht die gesonderte Herstellung der Triarylphosphinhydrohalogenide überflüssig; es ermöglicht hierdurch nicht nur die Einsparung von Arbeits-,gängen, sondern läßt auch eine bessere Ausnutzung des Triarylphosphins zu.The process makes the separate preparation of the triarylphosphine hydrohalides superfluous; allows this not only saves work, aisles, but also allows better utilization of the triarylphosphine.
Die in den Beispielen genannten Teile sind Gewichtsteile.The parts mentioned in the examples are parts by weight.
3140 Teile Triphenylphosphin, 2640 Teile Vinyl-^-ionol 'und 800 Teile Methanol werden bei -)- 5° C unter lebhaftem jRühren mit der Lösung von 450 Teilen Chlorwasserstoff iin 6400 Teilen Methanol versetzt. Das Gemisch wird noch 2 Stunden bei +5° C und 20 Stunden bei Raumtemperatur gerührt. Diese Lösung wird gleichzeitig mit einer Lösung von 800 Teilen Kaliumhydroxyd in 4800 Teilen !Methanol bei —20cC in ein Gemisch von 1850 Teilen jS-Formylcrotonsäuremethylester und 1800 Teilen Methanol unter Stickstoff atmosphäre langsam eingegossen. Das !Reaktionsgemisch wird dann auf eine Temperatur von D0C gebracht und noch 5 Stunden gerührt. Dabei fällt ein kristalliner Niederschlag aus. Er wird abgeschleudert, gut mit Wasser gewaschen und getrocknet. Es werden 1860 Teile Vitamin A-säuremethylester erhalten, der nach einmaligem Umkristallisieren aus Methanol—Aceton einen Schmelzpunkt von 550C zeigt.3140 parts of triphenylphosphine, 2640 parts of vinyl - ^ - ionol 'and 800 parts of methanol are added at -) - 5 ° C with vigorous stirring with the solution of 450 parts of hydrogen chloride in 6400 parts of methanol. The mixture is stirred for a further 2 hours at + 5 ° C. and 20 hours at room temperature. This solution is treated with a solution of 800 parts of potassium hydroxide in 4800 parts! Methanol at -20 c C to a mixture of 1850 parts of jS-formylcrotonate and 1800 parts of methanol under a nitrogen atmosphere slowly poured simultaneously. The reaction mixture is then brought to a temperature of D 0 C and stirred for a further 5 hours. A crystalline precipitate separates out. It is spun off, washed well with water and dried. There are obtained 1860 parts of vitamin A-säuremethylester which after one recrystallization from methanol-acetone shows a melting point of 55 0 C.
Das Filtrat der Reaktionslösung wird mehrmals mit Petroläther extrahiert. Die vereinigten Petrolätherextrakte werden mit W'asser neutral ,gewaschen, vom dabei ausfallenden Niederschlag abfilitriert und über !Natriumsulfat getrocknet. Nach dem Abdestillieren des Petroläthers bleiben 2030 Teile Öl als Rückstand, das zu 50 °/o ebenfalls aus Vitamin A-säuremethylester besteht und durch fraktionierte Kurzwegdestillation gereinigt wird; Kp.0j005 135 bis 1370C, Ausbeute 920 Teile.The filtrate of the reaction solution is extracted several times with petroleum ether. The combined petroleum ether extracts are washed neutral with water, filtered off from the precipitate which separates out and dried over sodium sulfate. After the petroleum ether has been distilled off, 2030 parts of oil remain as residue, 50% of which also consists of vitamin A methyl ester and is purified by fractional short-path distillation; Bp . 0j005 135 to 137 0 C, yield 920 parts.
Die Gesamtausbeute beträgt 2780 Teile.The total yield is 2780 parts.
ίο Zu 22 Teilen Vinyl-ß-ionol und 26 Teilen Triphenylphosphin
wird bei 2O0C die Lösung von 3,7 Teilen Chlorwasserstoff
in 80 Teilen Methanol getropft. Dieses Gemisch wird 20 Stunden gerührt und dann gleichzeitig mit
der Lösung von 16 Teilen Natriummethylat in 45 Teilen Methanol unter Stickstoff bei —3O0C zur Lösung von
Teilen jS-Formylcrotonsäure in 40 Teilen Alkohol
gegeben. Dann wird die Kühlung abgestellt. Sobald das Reaktionsgemisch eine Temperatur von -(-150C erreicht
hat, werden 70 Teile einer 3normalen wäßrigen Salzsäure zugesetzt. Nach 15 Stunden wird der ausgefallene Niederschlag
abfiltriert. Der Rückstand wird gut mit Wasser gewaschen und im Vakuum getrocknet. Es werden
Teile rohe Vitamin Α-säure erhalten.
Aus der Mutterlauge können durch Versetzen mit Wasser nochmals 7 Teile rohe Vitamin Α-säure kristallin
erhalten werden. Die so erhaltenen 21 Teile Vitamin A-säure werden aus Methanol umkristallisiert; man erhält
Teile reine all-trans-Vitamin Α-säure vom F. 179
bis 1800C.ίο to 22 parts of vinyl-beta-ionol, and 26 parts of triphenylphosphine is at 2O 0 C the solution of 3.7 parts of hydrogen chloride in 80 parts of methanol added dropwise. This mixture is stirred for 20 hours and then added simultaneously with the solution of 16 parts of sodium in 45 parts of methanol under nitrogen at -3O 0 C to the solution of parts jS-Formylcrotonsäure in 40 parts of alcohol. Then the cooling is switched off. Once the reaction mixture to a temperature of - (- has reached 15 0 C, 70 parts of a 3normalen aqueous hydrochloric acid is added After 15 hours, the precipitate is filtered off, the residue is washed well with water and dried under vacuum to parts of crude vitamin... Α-acid obtained.
A further 7 parts of crude vitamin Α-acid can be obtained in crystalline form from the mother liquor by adding water. The 21 parts of vitamin A acid thus obtained are recrystallized from methanol; parts of pure all-trans-vitamin Α-acid with a temperature of 179 to 180 ° C. are obtained.
Xmax (Methanol) 350 bis 351 ηΐμ, e = 43000. Xmax (methanol) 350 to 351 ηΐμ, e = 43000.
Claims (4)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1068702B true DE1068702B (en) | 1959-11-12 |
Family
ID=593991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DENDAT1068702D Pending DE1068702B (en) | Process for the production of vitamin A and its biologically active derivatives |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1068702B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1129480B (en) * | 1960-07-01 | 1962-05-17 | Hoechst Ag | Process for the preparation of tetracyclic compounds |
-
0
- DE DENDAT1068702D patent/DE1068702B/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1129480B (en) * | 1960-07-01 | 1962-05-17 | Hoechst Ag | Process for the preparation of tetracyclic compounds |
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