CH389593A - Process for the preparation of 2-cis-B-ionylideneacetic acid - Google Patents
Process for the preparation of 2-cis-B-ionylideneacetic acidInfo
- Publication number
- CH389593A CH389593A CH7689059A CH7689059A CH389593A CH 389593 A CH389593 A CH 389593A CH 7689059 A CH7689059 A CH 7689059A CH 7689059 A CH7689059 A CH 7689059A CH 389593 A CH389593 A CH 389593A
- Authority
- CH
- Switzerland
- Prior art keywords
- cis
- acid
- ether
- methyl
- reaction
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims description 10
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 9
- 150000002596 lactones Chemical class 0.000 claims description 7
- 239000011701 zinc Substances 0.000 claims description 7
- 229910052725 zinc Inorganic materials 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 230000000269 nucleophilic effect Effects 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 230000008030 elimination Effects 0.000 claims description 2
- 238000003379 elimination reaction Methods 0.000 claims description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- MOQGCGNUWBPGTQ-UHFFFAOYSA-N 2,6,6-trimethyl-1-cyclohexene-1-carboxaldehyde Chemical compound CC1=C(C=O)C(C)(C)CCC1 MOQGCGNUWBPGTQ-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000006680 Reformatsky reaction Methods 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 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
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N anhydrous methyl formate Natural products COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 235000021466 carotenoid Nutrition 0.000 description 1
- 150000001747 carotenoids Chemical class 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C61/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C61/16—Unsaturated compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Verfahren zur Herstellung von 2-cis-P-Jonylidenessigsäure
Es wurde gefunden, dass man die 2-cis-ssJony- lidenessigsäure (V) erhält, wenn man ss-Cyclocitral (I) mit γ-Halogen-ss-methyl-crotonsäurenitril (II) in Gegenwart von Zink umsetzt und das gebildete (5-lmidolacton (III) in wässrigem Medium unter Ammoniakabspaltung in das Lacton (IV) überführt und dieses mit nucleophilen Agenzien behandelt.
Der Reaktionsverlauf kann durch folgendes Formelschema wiedergegeben werden:
EMI1.1
Als γ-Halogen-ss-methyl-crotonsäurenitrile kommen besonders die Brom-, Jod- und Chlorverbindungen in Frage.
Die Umsetzung des BCyclocitrals mit dem y-Ha logen-lS-methyl-crotonsäurenitril erfolgt in der Regel unter den Bedingungen der Reformatsky'schen Reaktion, indem man z. B. das SCyclocitral in einem Lösungsmittel, wie Tetrahydrofuran, Dioxan, Benzol, Toluol oder Gemischen dieser Lösungsmittel mit Di äthyläther, löst, das für die Umsetzung erforderliche Zink in einer der üblichen Formen, z. B. als Zinkstaub, Zinkwolle oder Zinkspäne, zugibt und dann das - gegebenenfalls in einem der oben erwähnten Lösungsmittel gelöste - γ-Halogen-ss-methyl-croton- säurenitril zusetzt, wobei man die Umsetzung vorteilhafterweise bei etwas erhöhter Temperatur vornimmt, z.
B. bei etwa 40-110 . Die Umsetzung kann aber auch so durchgeführt werden, dass man dem Zink ein Gemisch der gegebenenfalls in einem Lösungsmittel gelösten Reaktionskomponenten allmählich zusetzt.
Es kann dabei zur Erzielung guter Ausbeuten zweckmässig sein, das r-Halogen-ss-methyl-croton- säurenitril im Überschuss, bezogen auf das ss-Cyclocitral, einzusetzen. Dafür kommen 1,2-1,5 Mole Halogenkomponente pro Mol Cyclocitral in Frage.
Das Zink wird zweckmässig im Überschuss oder in einer der Halogenkomponente äquimolaren Menge eingesetzt.
Das bei dieser Umsetzung gebildete Reaktionsprodukt kann nach den üblichen Methoden der Reformatsky-Synthese aufgearbeitet werden, z. B. durch eine Behandlung mit verdünnten Säuren, z. B.
Salzsäure, Schwefelsäure, Phosphorsäure oder Essigsäure. Dabei enthält die saure wässrige Phase das Imidolacton als Salz gelöst, während ein in geringerer Ausbeute entstehendes Hydroxynitril leicht mit Äther extrahiert werden kann. Das Salz des Imidolactons kann nach üblichen Methoden isoliert werden, z. B. indem man die wässrige Lösung mit Natriumchlorid sättigt und das ausgesalzene Produkt mit einem Lösungsmittel, wie Ameisensäuremethyl- oder -äthylester, Essigsäuremethyl- oder -äthylester, Methylenchlorid, Chloroform, Tetrachlorkohlenstoff, Tetrahydrofuran oder Dioxan, ausschüttelt. Aus dem Salz kann man das freie Imidolacton nach üblichen Verfahren, z. B. durch eine Behandlung mit wässrigen Alkalien, wie Natronlauge, Kalilauge oder Lösungen von Kaliumcarbonat, Natriumcarbonat oder Natriumhydrogencarbonat, erhalten.
Die Überführung des Imidolactons in das Lacton kann durch eine Behandlung mit Wasser erfolgen, z. B. indem man das in einem organischen Lösungsmittel, z. B. Äther, gelöste Imidolacton mit Wasser schüttelt oder indem man das Imidolacton in wässrig alkoholischer Lösung kocht. Aus dem Lacton kann die 2-cis-ss-Jonylidenessigsäure durch die Behandlung mit nucleophilen Agenzien, wie z. B. Alkoholaten oder Alkaliamiden, in wasserfreiem Medium als Salz der ungesättigten Säure erhalten werden.
Die erfindungsgemäss erhaltene 2-cis-13-Jonyliden- essigsäure ist ein Zwischenprodukt für Carotinoid Synthesen.
Beispiel a) In einem Dreihalskolben mit Rückflusskühler, Thermometer, Tropftrichter, Rührer und Einleitungs- rohr für Stickstoff, erwärmt man das Gemisch aus 15,2 g ss-Cyclocitral und 20 ml abs. Tetrahydrofuran mit 11 g Zinkstaub (zweckmässig mit 2% der Salzsäure angeätzt, mit Wasser, äthanol, Aceton und schliesslich mit abs. Äther gewaschen und im Vakuum bei 1000 getrocknet) unter Rühren in einer Stickstoffatmosphäre auf etwa 700 und lässt dann das Gemisch von 22 g γ-Brom-ss-methyl-crotonsäurenitril und 20 mol abs. Tetrahydrofuran allmählich unter leichtem Erwärmen zutropfen, so dass der Kolbeninhalt lebhaft siedet.
Die Reaktionstemperatur beträgt 73-750. Wenn alles zugetropft und die Reaktion abgeklungen ist, erhitzt man zur Vervollständigung der Umsetzung noch 15-20 Minuten zum Sieden. Danach wird der Kolbeninhalt auf etwa 0 abgekühlt und unter Rühren mit etwa 100 ml Äther versetzt.
Nun lässt man unter Aussenkühlung 200-250 ml n Salzsäure zufliessen, überführt den Kolbeninhalt in einen Scheidetrichter, setzt noch etwa 100-150 ml Wasser hinzu, schüttelt gut durch, trennt die Phasen und schüttelt die Ätherphase noch zweimal mit n Salzsäure aus. Die vereinigten wässrigen Phasen werden bei 0 mit festem Natriumhydrogencarbonat bis zur schwach-alkalischen Reaktion versetzt. Man äthert das sich abscheidende ölige Reaktionsprodukt aus, wäscht die ätherische Lösung mit Wasser, trocknet sie über Natriumsulfat und verdampft den Äther unter vermindertem Druck. Man erhält etwa 19,5 g 6-I12:6',6¯TrimethyI-cyclohexen-( l')-yl-(l ')l-4-methyl- 5,6-dihydro-2-imino-1,2-pyran (83-84% d. Th.) als zähes, gelbes Öl.
Das Ultraviolett-Absorptionsspektrum zeigt das für 2 konjugierte Doppelbindungen charakteristische Maximum bei 223 m, u (E = 15500).
Das Infrarot-Absorptionsspektrum besitzt die für die N-H-Gruppe charakteristische Absorption bei 3200 cm-1, die für die -C=N-Bindung charakteristische Absorption bei 1660 cm-1 und die für die dazu in Konjugation stehende -C=C-Bindung charakteristische Absorption bei 1615 cm-1. b) Man versetzt die Lösung von 4 g des nach a) erhaltenen Imidolactons in 37 ml Äthanol mit 28 ml Wasser und erhitzt das Gemisch etwa 15 Stunden in einer Stickstoffatmosphäre am Rückflusskühler zum Sieden, wobei Ammoniak entweicht. Man verdampft den Alkohol zum grössten Teil unter vermindertem Druck, verdünnt den Rückstand mit Wasser und schüttelt mehrfach mit Äther aus.
Die ätherische Lösung wird zunächst mit 10% iger Schwefelsäure, dann mit Wasser und schliesslich mit Natriumhydrogencarbonatlösung gewaschen, zuletzt über Natriumsulfat getrocknet. Nach dem Verdampfen des ethers verbleiben etwa 3,6 g (= 90 ; d. Th.) des Lactons der 5-[2',6',6'-Trimethyl-cyclohexen-(1')-yl-(1')]-5-hy droxy-3-methyl-penten-(2)-säure-(1), das aus seiner tiefgekühlten Lösung in Petroläther und wenig Äther auskristallisiert. Fp. 813.
Das Ultraviolett-Absorptionsmaximum liegt bei 217 m (log # = 4,1).
Analyse: Cl5H2202 (Molekulargewicht: 234,3) ber.: C = 76, 88 S H 9,47 % O = 13,66% gef.: C = 77,06% H 9,40% O = 13,90%
Zum gleichen Ergebnis gelangt man, wenn man die ätherische Lösung des Imidolactons mit gegebenenfalls schwach angesäuertem Wasser 15-20 Stunden schüttelt und Ätherphase wie oben angegeben aufarbeitet. c) Die Lösung von 30 g des in Beispiel b) erhaltenen Lactons in 180 ml abs. Äthanol erwärmt man mit der Lösung von 7,5 g Natrium in 180 ml abs.
Äthanol 1 Stunde am Rückflusskühler auf dem siedenden Wasserbad oder lässt die Lösung 5-10 Stunden bei Zimmertemperatur stehen. Man verdampft dann den grössten Teil des Äthanols unter reduziertem Druck und löst den Rückstand in Wasser. Durch Zugabe von 10% iger Phosphorsäure wird die 2-cis-jJ- Jonylidenessigsäure gefällt. Ausbeute etwa 30 g (nahezu quantitativ) ; Fp.: 103-104 (aus Äther + Petroläther).
Process for the preparation of 2-cis-P-ionylideneacetic acid
It has been found that 2-cis-ss-jonylideneacetic acid (V) is obtained when ss-cyclocitral (I) is reacted with γ-halo-ss-methyl-crotononitrile (II) in the presence of zinc and the ( 5-imidolactone (III) is converted into the lactone (IV) in an aqueous medium with elimination of ammonia and this is treated with nucleophilic agents.
The course of the reaction can be represented by the following equation:
EMI1.1
The bromine, iodine and chlorine compounds are particularly suitable as γ-halo-β-methyl-crotononitriles.
The implementation of BCyclocitrals with the y-halogen-IS-methyl-crotonsäurenitril is usually carried out under the conditions of the Reformatsky reaction by z. B. the SCyclocitral in a solvent such as tetrahydrofuran, dioxane, benzene, toluene or mixtures of these solvents with diethyl ether, dissolves, the zinc required for the reaction in one of the usual forms, eg. B. as zinc dust, zinc wool or zinc shavings, and then the γ-halo-β-methyl-crotonic acid nitrile - optionally dissolved in one of the above-mentioned solvents - is added, the reaction being carried out advantageously at a somewhat elevated temperature, e.g.
B. at about 40-110. The reaction can, however, also be carried out in such a way that a mixture of the reaction components, optionally dissolved in a solvent, is gradually added to the zinc.
In order to achieve good yields, it can be advantageous to use the r-halo-ß-methyl-crotonic acid nitrile in excess, based on the ß-cyclocitral. 1.2-1.5 moles of halogen component per mole of cyclocitral are suitable for this.
The zinc is expediently used in excess or in an amount equimolar to the halogen component.
The reaction product formed in this reaction can be worked up by the usual methods of Reformatsky synthesis, eg. B. by treatment with dilute acids, e.g. B.
Hydrochloric acid, sulfuric acid, phosphoric acid or acetic acid. The acidic aqueous phase contains the imidolactone dissolved as a salt, while a hydroxynitrile which is produced in a lower yield can easily be extracted with ether. The salt of imidolactone can be isolated by customary methods, e.g. B. by saturating the aqueous solution with sodium chloride and shaking the salted out product with a solvent such as methyl or ethyl formate, methyl or ethyl acetate, methylene chloride, chloroform, carbon tetrachloride, tetrahydrofuran or dioxane. The free imidolactone can be obtained from the salt by conventional methods, e.g. B. by treatment with aqueous alkalis, such as sodium hydroxide solution, potassium hydroxide solution or solutions of potassium carbonate, sodium carbonate or sodium hydrogen carbonate.
The conversion of the imidolactone into the lactone can be carried out by treatment with water, e.g. B. by doing this in an organic solvent, e.g. B. ether, shaking dissolved imidolactone with water or by boiling the imidolactone in an aqueous alcoholic solution. The 2-cis-ss-Jonylidenessigsäure can be obtained from the lactone by treatment with nucleophilic agents, such as. B. alcoholates or alkali amides, can be obtained in an anhydrous medium as a salt of the unsaturated acid.
The 2-cis-13-ionylideneacetic acid obtained according to the invention is an intermediate product for carotenoid syntheses.
Example a) In a three-necked flask equipped with a reflux condenser, thermometer, dropping funnel, stirrer and inlet pipe for nitrogen, the mixture of 15.2 g of ss-cyclocitral and 20 ml of abs. Tetrahydrofuran with 11 g of zinc dust (expediently etched with 2% hydrochloric acid, washed with water, ethanol, acetone and finally with absolute ether and dried in vacuo at 1000) while stirring in a nitrogen atmosphere to about 700 and then leaves the mixture of 22 g γ-bromo-ss-methyl-crotononitrile and 20 mol abs. Gradually add the tetrahydrofuran dropwise with slight warming so that the contents of the flask boil vigorously.
The reaction temperature is 73-750. When everything has been added dropwise and the reaction has subsided, the mixture is heated to boiling for 15-20 minutes to complete the reaction. The contents of the flask are then cooled to about 0 and about 100 ml of ether are added while stirring.
Now 200-250 ml of normal hydrochloric acid are allowed to flow in with external cooling, the contents of the flask are transferred to a separating funnel, about 100-150 ml of water are added, the phases are shaken well, the phases are separated and the ether phase is extracted twice more with hydrochloric acid. Solid sodium hydrogen carbonate is added to the combined aqueous phases at 0 until a weakly alkaline reaction occurs. The oily reaction product which separates out is etherified, the ethereal solution is washed with water, dried over sodium sulphate and the ether is evaporated off under reduced pressure. About 19.5 g of 6-112: 6 ', 6¯trimethyI-cyclohexen- (l') -yl- (l ') l-4-methyl-5,6-dihydro-2-imino-1,2 are obtained -pyran (83-84% of theory) as a viscous, yellow oil.
The ultraviolet absorption spectrum shows the maximum characteristic of 2 conjugated double bonds at 223 m, u (E = 15500).
The infrared absorption spectrum has the absorption at 3200 cm-1, which is characteristic for the NH group, the absorption at 1660 cm-1 which is characteristic for the -C = N bond and the characteristic for the conjugated -C = C bond Absorption at 1615 cm-1. b) The solution of 4 g of the imidolactone obtained according to a) in 37 ml of ethanol is mixed with 28 ml of water and the mixture is heated to boiling for about 15 hours in a nitrogen atmosphere on a reflux condenser, ammonia escaping. Most of the alcohol is evaporated under reduced pressure, the residue is diluted with water and extracted several times with ether.
The ethereal solution is washed first with 10% sulfuric acid, then with water and finally with sodium hydrogen carbonate solution, and finally dried over sodium sulfate. After the ether has evaporated, about 3.6 g (= 90; d. Th.) Of the lactone of the 5- [2 ', 6', 6'-trimethyl-cyclohexen- (1 ') -yl- (1') ] -5-hy droxy-3-methyl-pentene (2) acid (1), which crystallizes out of its frozen solution in petroleum ether and a little ether. M.p. 813.
The ultraviolet absorption maximum is 217 m (log # = 4.1).
Analysis: Cl5H2202 (molecular weight: 234.3) calc .: C = 76.88 S H 9.47% O = 13.66% found: C = 77.06% H 9.40% O = 13.90%
The same result is obtained if the ethereal solution of imidolactone is shaken with slightly acidic water, if necessary, for 15-20 hours and the ether phase is worked up as indicated above. c) The solution of 30 g of the lactone obtained in Example b) in 180 ml of abs. Ethanol is heated with the solution of 7.5 g of sodium in 180 ml of abs.
Ethanol for 1 hour on the reflux condenser on a boiling water bath or let the solution stand for 5-10 hours at room temperature. Most of the ethanol is then evaporated off under reduced pressure and the residue is dissolved in water. The 2-cis-jJ-ionylideneacetic acid is precipitated by adding 10% phosphoric acid. Yield about 30 g (almost quantitative); Fp .: 103-104 (from ether + petroleum ether).
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEF0026446 | 1958-08-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH389593A true CH389593A (en) | 1965-03-31 |
Family
ID=7092029
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH7689059A CH389593A (en) | 1958-08-20 | 1959-08-12 | Process for the preparation of 2-cis-B-ionylideneacetic acid |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH389593A (en) |
-
1959
- 1959-08-12 CH CH7689059A patent/CH389593A/en unknown
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