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EP0000907B1 - Process for the preparation of furanones and intermediate products in this process - Google Patents

Process for the preparation of furanones and intermediate products in this process Download PDF

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Publication number
EP0000907B1
EP0000907B1 EP78100650A EP78100650A EP0000907B1 EP 0000907 B1 EP0000907 B1 EP 0000907B1 EP 78100650 A EP78100650 A EP 78100650A EP 78100650 A EP78100650 A EP 78100650A EP 0000907 B1 EP0000907 B1 EP 0000907B1
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EP
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Prior art keywords
cyano
ethyl
compound
hydroxy
methyl
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EP78100650A
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German (de)
French (fr)
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EP0000907A1 (en
Inventor
Ulrich Dr. Huber
Hans Jakob Dr. Wild
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Givaudan SA
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L Givaudan and Co SA
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Priority claimed from LU77955A external-priority patent/LU77955A1/en
Priority claimed from LU78691A external-priority patent/LU78691A1/en
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Publication of EP0000907A1 publication Critical patent/EP0000907A1/en
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    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
    • A23L27/20—Synthetic spices, flavouring agents or condiments
    • A23L27/205—Heterocyclic compounds
    • A23L27/2052—Heterocyclic compounds having oxygen or sulfur as the only hetero atoms
    • 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
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
    • C07D307/60—Two oxygen atoms, e.g. succinic anhydride

Definitions

  • the invention relates to a new process for the preparation of furanones, namely those of the general formula wherein R is hydrogen, methyl or ethyl; the radicals R can be the same or different.
  • the process according to the invention is characterized in that a compound of the general formula wherein R has the above meaning, the thermal or base-catalyzed cyanohydrin cleavage.
  • the compound of formula II is expediently heated to temperatures of about 50 to 400 ° C., in particular to about 80-250 ° C.
  • the compound of the formula II is advantageously mixed with catalytic amounts, e.g. with 1 / 1000-1 / 10 equivalents, or also with larger ones, e.g. molar amounts of a base.
  • Suitable bases are, for example: inorganic bases such as alkali metal hydroxides, for example NaOH, alkaline earth metal hydroxides, for example Ca (OH) 2 , Mg (OH) 2 , alkali metal carbonates, for example Na 2 CO 3 , K 2 CO 3 , alkali metal bicarbonates such as NaHCO 3 , ammonia, other basic salts such as Na 3 , P0 4 , K 2 HPO 4 , borax, basic buffer systems such as NaHCO 3 / Na 2 CO 3 , K 2 HPO 4 / K 3 PO 4 , etc., organic bases such as amines, e.g.
  • inorganic bases such as alkali metal hydroxides, for example NaOH, alkaline earth metal hydroxides, for example Ca (OH) 2 , Mg (OH) 2
  • alkali metal carbonates for example Na 2 CO 3 , K 2 CO 3
  • alkali metal bicarbonates such as NaHCO 3 , ammonia
  • triethylamine Pyridine, morpholine, etc.
  • salts of organic acids with strong bases such as sodium acetate, formate, oxalate, citrate, lactate, or basic ion exchangers, e.g. Amberlite JRA 400e, Dowex 2e, etc.
  • the cyanohydrin cleavage can be carried out in the gas phase or in the liquid phase.
  • the presence of a solvent is not necessary, but is advisable.
  • Possible reaction temperatures are in particular 50-200 ° C., preferably approx. 100 ° C.
  • polar solvents such as water, ammonia, alcohols, or apolar solvents such as toluene, benzene, toluene, ether, petroleum ether, etc., can be used.
  • Preferred systems are basic ion exchangers in the OH e form / H 2 O, or salts of organic acids, such as sodium oxalate / H 2 O, or pyridine / toluene at reaction temperatures of around 100 ° C.
  • the compounds of the formula II can advantageously be obtained by oxidation of compounds of the formula where R has the above meaning can be obtained.
  • Alkali metal caroates for example KH SO 5
  • KH SO 5 are particularly suitable as oxidizing agents.
  • "Caroat” ® KHSO s with small amounts of KHSO 4 and K 2 SO 4 ) is preferred.
  • the caroate is expediently used in an amount of 1-2.5 equivalents, in particular 1.1-1.5 equivalents.
  • the oxidation is preferably carried out in polar solvents, such as water, alcohols, acetone, acetonitrile, or mixtures of such solvents.
  • polar solvents such as water, alcohols, acetone, acetonitrile, or mixtures of such solvents.
  • the pH of the medium is expediently about 3-11, as can be produced in a manner known per se by appropriate buffer systems of the carbonate, phosphate, citrate, borate, NH 3 / NH + 4 or oxalate type.
  • the reaction temperature can be, for example, between -10 to 60 ° C, preferably between 0 to 20 ° C.
  • the compounds of formula III can advantageously by reacting a compound of formula with a compound of the formula wherein R has the above meaning and R 1 represents lower alkyl, are obtained.
  • the reaction of the substituted acrylonitrile IV with the acid ester V is expediently carried out at elevated temperature, for example at 40-100 ° C., in particular at temperatures around 60 ° C.
  • the reaction can also be carried out at a lower temperature, for example at room temperature. At this temperature, however, the formation of by-products is observed, which are removed again when III is worked up must, for example by washing out in a weakly basic environment.
  • the molar ratio of compound IV to compound V is preferably 1: 1.
  • a strong base for example a hydride such as NaH, an amide such as KNH 2 , etc. a hydroxide such as NaOH, an alcoholate such as NaOC 2 H 5 , KO or a metal such as Na, K is used.
  • a strong base for example a hydride such as NaH, an amide such as KNH 2 , etc.
  • a hydroxide such as NaOH, an alcoholate such as NaOC 2 H 5 , KO or a metal such as Na, K is used.
  • Particularly suitable solvents are polar, preferably aprotic, solvents.
  • ethers such as tetrahydrofuran, dioxane, diglyme, diethyl ether, diisopropyl ether, nitro compounds such as nitromethane, nitrobenzene, nitriles such as acetonitrile, or dimethylformamide, dimethyl sulfoxide, etc.
  • ethers especially preferred are ethers.
  • protic solvents examples include alcohols such as tert. Butyl alcohol or isopropanol.
  • the compounds of the formula are known; they represent flavorings. They have so far been produced, for example, by ozonization of alkynediols and acid cyclization of the dioxodiols obtained. [Re et al., Helv. Chim. Acta 56, 1882 (1973)].
  • the process has the disadvantages that a) primarily unstable ozonides are formed (which can explode) and the acid cyclization stage produces unsatisfactory yields.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Nutrition Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Furan Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Seasonings (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

Die Erfindung betrifft ein neues Verfahren zur Herstellung von Furanonen, und zwar solchen der allgemeinen Formel

Figure imgb0001
worin R Wasserstoff, Methyl oder Aethyl bedeutet; die Reste R können gleich oder verschieden sein.The invention relates to a new process for the preparation of furanones, namely those of the general formula
Figure imgb0001
 wherein R is hydrogen, methyl or ethyl; the radicals R can be the same or different.

Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man eine Verbindung der allgemeinen Formel

Figure imgb0002
worin R obige Bedeutung besitzt, der thermischen oder basenkatalysierten Cyanhydrinspaltung unterwirft.The process according to the invention is characterized in that a compound of the general formula
Figure imgb0002
 wherein R has the above meaning, the thermal or base-catalyzed cyanohydrin cleavage.

Im Falle der thermischen Durchführung erhitzt man die Verbindung der Formel II zweckmässigerweise auf Temperaturen von ca. 50 bis 400°C, insbesondere auf ca. 80-250°C.In the case of thermal implementation, the compound of formula II is expediently heated to temperatures of about 50 to 400 ° C., in particular to about 80-250 ° C.

Im Falle der basenkatalytischen Cyanhydrinspaltung versetzt man die Verbindung der Formel II, zweckmässigerweise mit katalytischen Mengen, z.B. mit 1/1000-1/10 Aequivalenten, oder aber auch mit grösseren, z.B. molaren Mengen einer Base.In the case of base catalytic cyanohydrin cleavage, the compound of the formula II is advantageously mixed with catalytic amounts, e.g. with 1 / 1000-1 / 10 equivalents, or also with larger ones, e.g. molar amounts of a base.

Die Natur der Base ist nicht kritisch. Als Basen kommen z.B. in Frage: anorganische Basen wie Alkalimetallhydroxyde, z.B. NaOH, Erdalkalimetallhydroxyde, z.B. Ca(OH)2, Mg(OH)2, Alkalimetallcarbonate, z.B. Na2CO3, K2CO3, Alkalimetallbicarbonate wie NaHCO3, Ammoniak, andere basische Salze wie Na3, P04, K2HPO4, Borax, basische Puffersysteme wie z.B. NaHCO3/Na2CO3, K2HPO4/K3PO4, etc., organische Basen wie Amine, z.B. Triäthylamin, Pyridin, Morpholin, etc., Salze organischer Säuren mit starken Basen, wie Natriumacetat, -format, -oxalat, -citrat, -lactat, oder basische lonentauscher, z.B. Amberlite JRA 400e, Dowex 2e, etc.The nature of the base is not critical. Suitable bases are, for example: inorganic bases such as alkali metal hydroxides, for example NaOH, alkaline earth metal hydroxides, for example Ca (OH) 2 , Mg (OH) 2 , alkali metal carbonates, for example Na 2 CO 3 , K 2 CO 3 , alkali metal bicarbonates such as NaHCO 3 , ammonia, other basic salts such as Na 3 , P0 4 , K 2 HPO 4 , borax, basic buffer systems such as NaHCO 3 / Na 2 CO 3 , K 2 HPO 4 / K 3 PO 4 , etc., organic bases such as amines, e.g. triethylamine, Pyridine, morpholine, etc., salts of organic acids with strong bases, such as sodium acetate, formate, oxalate, citrate, lactate, or basic ion exchangers, e.g. Amberlite JRA 400e, Dowex 2e, etc.

Die Cyanhydrinspaltung kann in der Gasphase oder in flüssiger Phase durchgeführt werden. Anwesenheit eines Lösungsmittels ist nicht erforderlich, jedoch zweckmässig.The cyanohydrin cleavage can be carried out in the gas phase or in the liquid phase. The presence of a solvent is not necessary, but is advisable.

Als Reaktionstemperaturen kommen insbesondere 50-200°C, bevorzugt ca. 100°C in Frage.Possible reaction temperatures are in particular 50-200 ° C., preferably approx. 100 ° C.

Die Natur des Lösungsmittels ist nicht kritisch, es können polare Lösungsmittel - wie Wasser, Ammoniak, Alkohole, oder apolare Lösungsmittel, wie Toluol, Benzol, Toluol, Aether, Petroläther, etc., zur Verwendung gelangen.The nature of the solvent is not critical, polar solvents - such as water, ammonia, alcohols, or apolar solvents such as toluene, benzene, toluene, ether, petroleum ether, etc., can be used.

Bevorzugte Systeme sind basische Ionentauscher in der OHe - Form/H20, oder Salze organischer Säuren, wie Natrium- oxalat/H2O, oder Pyridin/Toluol bei Reaktions- temperature'n von rund 100°C.Preferred systems are basic ion exchangers in the OH e form / H 2 O, or salts of organic acids, such as sodium oxalate / H 2 O, or pyridine / toluene at reaction temperatures of around 100 ° C.

Die Verbindungen der Formel II sind neu. Sie bilden ebenfalls Gegenstand der vorliegenden Erfindung.The compounds of formula II are new. They also form the subject of the present invention.

Die Verbindungen der Formel II können vorteilhaft durch Oxydation von Verbindungen der Formel

Figure imgb0003
worin R obige Bedeutung besitzt, erhalten werden.The compounds of the formula II can advantageously be obtained by oxidation of compounds of the formula
Figure imgb0003
 where R has the above meaning can be obtained.

Als Oxydationsmittel sind insbesondere Alkalimetallcaroate, z.B. KH SO5, geeignet. Bevorzugt ist "Caroat"® (KHSOs mit geringen Mengen KHSO4 und K2SO4).Alkali metal caroates, for example KH SO 5 , are particularly suitable as oxidizing agents. "Caroat" ® (KHSO s with small amounts of KHSO 4 and K 2 SO 4 ) is preferred.

Das Caroat wird zweckmässigerweise in einer Menge von 1-2,5 Aequivalenten, insbesondere 1,1-1,5 Aequivalenten, verwendet.The caroate is expediently used in an amount of 1-2.5 equivalents, in particular 1.1-1.5 equivalents.

Die Oxydation wird vorzugsweise in polaren Lösungsmitteln, wie Wasser, Alkoholen, Aceton, Acetonitril, oder Gemischen solcher Lösungsmittel durchgeführt.The oxidation is preferably carried out in polar solvents, such as water, alcohols, acetone, acetonitrile, or mixtures of such solvents.

Der pH-Wert des Mediums beträgt zweckmässigerweise ca. 3-11, wie dies durch entsprechende Puffersysteme vom Carbonat-, Phosphat-, Citrat-, Borat-, NH3/NH+ 4- oder Oxalattyp in an sich bekannter Weise erzeugt werden kann.The pH of the medium is expediently about 3-11, as can be produced in a manner known per se by appropriate buffer systems of the carbonate, phosphate, citrate, borate, NH 3 / NH + 4 or oxalate type.

Die Reaktionstemperatur kann beispielsweise zwischen -10 bis 60°C, bevorzugt zwischen 0 bis 20°C liegen.The reaction temperature can be, for example, between -10 to 60 ° C, preferably between 0 to 20 ° C.

Die Verbindungen der Formel III können vorteilhaft durch Umsetzung einer Verbindung der Formel

Figure imgb0004
mit einer Verbindung der Formel
Figure imgb0005
worin R obige Bedeutung besitzt und R1 nieder-Alkyl darstellt, erhalten werden.The compounds of formula III can advantageously by reacting a compound of formula
Figure imgb0004
 with a compound of the formula
Figure imgb0005
 wherein R has the above meaning and R 1 represents lower alkyl, are obtained.

Die Umsetzung der substituierten Acrylsäurenitrils IV mit dem Säureester V erfolgt zweckmässigerweise bei erhöhter Temperatur, beispielsweise bei 40-100°C, insbesondere bei Temperaturen um 60°C. Die Umsetzung lässt sich auch bei tieferer Temperatur, z.B. bei Zimmertemperatur durchführen. Bei dieser Temperatur wird aber die Bildung von Nebenprodukten beobachtet, welche bei der Aufarbeitung von III wieder entfernt werden müssen, z.B. durch Auswaschen in schwach basischem Milieu.The reaction of the substituted acrylonitrile IV with the acid ester V is expediently carried out at elevated temperature, for example at 40-100 ° C., in particular at temperatures around 60 ° C. The reaction can also be carried out at a lower temperature, for example at room temperature. At this temperature, however, the formation of by-products is observed, which are removed again when III is worked up must, for example by washing out in a weakly basic environment.

Das molare Verhältnis von Verbindung IV zu Verbindung V beträgt vorzugsweise 1:1.The molar ratio of compound IV to compound V is preferably 1: 1.

Man arbeitet zweckmässigerweise in Gegenwart einer Base und in einem Lösungsmittel.It is convenient to work in the presence of a base and in a solvent.

Als Base werden zweckmässigerweise 1-2 Aequivalente, insbesondere 1-1,3 Aequivalente einer starken Base, z.B. eines Hydrids wie NaH, eines Amids wie KNH2,

Figure imgb0006
etc. eines Hydroxyds wie NaOH, eines Alkoholats wie NaOC2H5, KO
Figure imgb0007
oder eines Metalls wie Na, K verwendet.Appropriately, 1-2 equivalents, in particular 1-1.3 equivalents, of a strong base, for example a hydride such as NaH, an amide such as KNH 2 ,
Figure imgb0006
 etc. a hydroxide such as NaOH, an alcoholate such as NaOC 2 H 5 , KO
Figure imgb0007
 or a metal such as Na, K is used.

Als Lösungsmittel kommen insbesondere polare, bevorzugt aprotische Lösungsmittel in Frage.Particularly suitable solvents are polar, preferably aprotic, solvents.

Beispiele sind Aether, wie Tetrahydrofuran, Dioxan, Diglyme, Diäthyläther, Diisopropyläther, Nitroverbindungen wie Nitromethan, Nitrobenzol, Nitrile wie Acetonitril, oder Dimethylformamid, Dimethylsulfoxyd, etc. Speziell bevorzugt sind Aether.Examples are ethers, such as tetrahydrofuran, dioxane, diglyme, diethyl ether, diisopropyl ether, nitro compounds such as nitromethane, nitrobenzene, nitriles such as acetonitrile, or dimethylformamide, dimethyl sulfoxide, etc. Especially preferred are ethers.

Beispiele von protischen Lösungsmitteln sind Alkohole wie tert. Butylalkohol oder lsopropanol.Examples of protic solvents are alcohols such as tert. Butyl alcohol or isopropanol.

Die Verbindungen der Formel sind bekannt; sie stellen Geschmackstoffe dar. Sie wurden bisher beispielsweise durch Ozonisierung von Alkindiolen und säure Cyclisierung der erhaltenen Dioxodiole hergestellt. [Re et al., Helv. Chim. Acta 56, 1882 (1973)]. Dem Verfahren haften die Nachteile an, dass a) primär unstabile Ozonide entstehen (die explodieren können) und die säure Cyclisierungsstufe unbefriedigende Ausbeuten zeitigt.The compounds of the formula are known; they represent flavorings. They have so far been produced, for example, by ozonization of alkynediols and acid cyclization of the dioxodiols obtained. [Re et al., Helv. Chim. Acta 56, 1882 (1973)]. The process has the disadvantages that a) primarily unstable ozonides are formed (which can explode) and the acid cyclization stage produces unsatisfactory yields.

Beispiel 1example 1

  • a) Zu 24 g (1 Mol) Natriumhydrid in 500 ml Tetrahydrofuran werden 130 g (1.1 Mol) Milchsäureäthylester zugetropft. Zu der graubraunen Lösung werden nun bei Rückflusstemperatur 73,7 g (1.1 Mol) Crotonsäurenitril in 60 ml Tetrahydrofuran gegeben und das Gemisch weitere 90 Minuten rückflussiert. Die erkaltete Reaktionslösung wird mit 250 ml 5n HCI versetzt und dreimal mit Aether extrahiert. Die vereinigten Aetherphasen werden dreimal mit Wasser gewaschen, mit Natriumsulfat getrocknet und eingeengt, wobei man 133,6 g (96% Ausbeute) 2,5-Dimethyl-4-cyano-tetrahydrofuran-3-on erhält, Sdp. 109-111 1°C/18 Torr. Gaschromatographische Identifizierung (GC) an 3m-Säule, 2% Carbowax auf Chromosorb: bei 200°C werden Retentionszeiten von 2.9 und 3.2 Minuten gemessen (Diastereomerengemisch), n20 D = 1.450.a) 130 g (1.1 mol) of lactic acid ethyl ester are added dropwise to 24 g (1 mol) of sodium hydride in 500 ml of tetrahydrofuran. 73.7 g (1.1 mol) of crotonic acid nitrile in 60 ml of tetrahydrofuran are then added to the gray-brown solution at reflux temperature and the mixture is refluxed for a further 90 minutes. The cooled reaction solution is mixed with 250 ml of 5N HCl and extracted three times with ether. The combined ether phases are washed three times with water, dried with sodium sulfate and concentrated to give 133.6 g (96% yield) of 2,5-dimethyl-4-cyano-tetrahydrofuran-3-one, b.p. 109-111 1 ° C / 18 torr. Gas chromatographic identification (GC) on a 3m column, 2% Carbowax on Chromosorb: retention times of 2.9 and 3.2 minutes are measured at 200 ° C (mixture of diastereomers), n 20 D = 1,450.
  • b) In einem Kolben werden 7 g des oben erhaltenen cyclischen Nitrils und 21 g NaHC03 in 400 ml Wasser gelöst und bei 10°C mit einer Lösung von 25 g "Caroat" (Degussa) in 80 ml Wasser versetzt und nach 30 Minuten viermal mit je 150 ml Essigester extrahiert. Die vereinigten organischen Phasen werden über Na2S04 getrocknet und eingeengt, wobei 4,3 g eines Diastereomerengemisches von 2,5-Dimethyl - 4 - hydroxy - 4 - cyano - tetrahydrofuran - 3 - on (55% Ausbeute) erhalten werden. Sdp. - 95°/0.04 Torr, n20 D = 1.468.b) 7 g of the cyclic nitrile obtained above and 21 g of NaHC0 3 are dissolved in 400 ml of water in a flask and a solution of 25 g of "Caroat" (Degussa) in 80 ml of water is added at 10 ° C. and four times after 30 minutes extracted with 150 ml of ethyl acetate. The combined organic phases are dried over Na 2 SO 4 and concentrated, giving 4.3 g of a mixture of diastereomers of 2,5-dimethyl-4-hydroxy-4-cyano-tetrahydrofuran-3-one (55% yield). Bp - 95 ° / 0.04 torr, n 20 D = 1,468.

IR 3400 nm (stark), 3010 nm, 2970 und 2910 nm (Dublett), 2280 nm (schwach), 1790 nm (mittel), 1385 nm (stark), 1110 nm (stark).

  • c1) 5 g des obigen Cyanhydrins und 7.5 g Ionentauscher Dowex 2 (OH⊖Form) werden während einer Stunde in 30 ml Wasser rückflussiert, darauf wird filtriert. Das Filtrat wird mit Kochsalz gesättigt und viermal mit je 80 ml Essigester extrahiert. Die vereinigten, über Na2S04 getrockneten, organischen Phasen werden eingeengt und ergeben 2 g (50% Ausbeute) eines Oeles, welches beim Stehen auskristallisiert. Durch Dünnschichtchromatographie und NMR wird Identität mit 4-Hydroxy-. 2,5-dimethyl-3(2H)-furanon nachgewiesen.
  • c2) 1 g des obigen Cyanhydrins und 0,7 g Triäthylamin werden in 10 ml Toluol während 15 Minuten rückflussiert. Nun gibt man 5 g Kieselgel (Merck) zu und filtriert ab. Die eingeengte Lösung ergibt 0.34 g 4-Hydroxy-2,5-dimethyl-3(2H)-furanon.
IR 3400 nm (strong), 3010 nm, 2970 and 2910 nm (doublet), 2280 nm (weak), 1790 nm (medium), 1385 nm (strong), 1110 nm (strong).
  • c 1 ) 5 g of the above cyanohydrin and 7.5 g of ion exchanger Dowex 2 (OH⊖Form) are refluxed in 30 ml of water for one hour, then it is filtered. The filtrate is saturated with sodium chloride and extracted four times with 80 ml of ethyl acetate. The combined, organic phases dried over Na 2 SO 4 are concentrated and give 2 g (50% yield) of an oil which crystallizes on standing. By thin layer chromatography and NMR identity with 4-hydroxy-. Detected 2,5-dimethyl-3 (2H) furanon.
  • c 2 ) 1 g of the above cyanohydrin and 0.7 g of triethylamine are refluxed in 10 ml of toluene for 15 minutes. Now add 5 g of silica gel (Merck) and filter off. The concentrated solution gives 0.34 g of 4-hydroxy-2,5-dimethyl-3 (2H) -furanone.

Beispiel 2Example 2

  • a) Zu 12 g (0.5 Mol) Natriumhydrid in 500 ml Tetrahydrofuran werden 72.6 g (0.55 Mol) Glykolsäurebutylester getropft. Das entstandene grünbraune Reaktionsgemisch wird unter Rückflusstemperatur mit 36.9 g Crotonsäurenitril in 50 ml Tetrahydrofuran versetzt und 90 Minuten bei Rückflusstemperatur gehalten. Das erkaltete Reaktionsgemisch wird mit NaHC03-Lösung auf pH 9 gestellt und dreimal mit Aether gewaschen. Die wässerige Phase wird mit HCI auf pH 1 angesäuert und mit Aether viermal extrahiert. Die getrockneten und eingeengten Aetherphasen ergeben 29,1 g des 4-Cyano-5-methyl-tetrahydrofuran-3-ons. Sdp 112-116°C/13 Torr, GC (Carbowax, 180°C) ein Peak, IR (Film): 2250 (m)-CN; 1783 (s)
    Figure imgb0008
         a) 72.6 g (0.55 mol) of butyl glycolate are added dropwise to 12 g (0.5 mol) of sodium hydride in 500 ml of tetrahydrofuran. 36.9 g of crotonic acid nitrile in 50 ml of tetrahydrofuran are added to the resulting green-brown reaction mixture at reflux temperature and the mixture is kept at the reflux temperature for 90 minutes. The cooled reaction mixture is adjusted to pH 9 with NaHC0 3 solution and washed three times with ether. The aqueous phase is acidified to pH 1 with HCl and extracted four times with ether. The dried and concentrated ether phases yield 29.1 g of the 4-cyano-5-methyl-tetrahydrofuran-3-one. Bp 112-116 ° C / 13 torr, GC (Carbowax, 180 ° C) a peak, IR (film): 2250 (m) -CN; 1783 (s)
    Figure imgb0008
  • b) In einem Kolben werden 3.1 g des oben erhaltenen cyclischen Nitrils, 10,5 g NaHCOa und 2 g NaOH in 30 ml Wasser gelöst und bei 15-20°C mit einer Lösung von 11 g Caroat (Degussa) in 35 ml Wasser versetzt. Nach 30 Minuten wird fünfmal mit je 35 ml Essigester extrahiert und die vereinigten Essigphasen werden getrocknet und eingeengt. Es werden 2,2 g (63% der Theorie) 4 - Cyano - 4 - hydroxy - 5 - methyl - tetrahydrofuran-3-on als hellbraunes Oel erhalten; GC: ein Peak. NMR (CDCl3) zeigt komplexe Multipletts zwischen 3.3-4.7 ppm und 1-1.8 ppm sowie ein OH-Signal bei 5.7 ppm.b) 3.1 g of the cyclic nitrile obtained above, 10.5 g of NaHCO a and 2 g of NaOH are dissolved in 30 ml of water and at 15-20 ° C. with a solution of 11 g of Caroat (Degussa) in 35 ml of water transferred. After 30 minutes, the mixture is extracted five times with 35 ml of ethyl acetate each time, and the combined vinegar phases are dried and concentrated. 2.2 g (63% of theory) of 4-cyano-4-hydroxy-5-methyl-tetrahydrofuran-3-one are obtained as a light brown oil; GC: a peak. NMR (CDCl 3 ) shows complex multiplets between 3.3-4.7 ppm and 1-1.8 ppm and an OH signal at 5.7 ppm.
  • c) 1.07 g des erhaltenen Cyanhydrins und 2.0 g Natriumglukonat werden in 15 ml Wasser während 15 Minuten rückflussiert. Nun wird fünfmal mit Essigester extrahiert, die Essigesterphasen getrocknet und eingeengt, wobei 0.42 g 4 - Hydroxy - 5 - methyl - 3(2H) - furanon erhalten werden. Das umkristallisierte Material (Smp. 111-1200C) zeigt folgendes NMR (CDCl3): 7.3 ppm (Singulett 1 H, OH): 4.5-4.65 ppm (Multiplett 3 H, CH3).c) 1.07 g of the cyanohydrin obtained and 2.0 g of sodium gluconate are refluxed in 15 ml of water for 15 minutes. The mixture is then extracted five times with ethyl acetate, the ethyl acetate phases are dried and concentrated to give 0.42 g of 4-hydroxy-5-methyl-3 (2H) -furanone. The recrystallized material (mp. 111-120 0 C) shows the following NMR (CDCl 3 ): 7.3 ppm (singlet 1 H, OH): 4.5-4.65 ppm (multiplet 3 H, CH 3 ).
Beispiel 3Example 3

  • a) 8,7 g (0,2 Mol) Natriumhydrid werden in 100 ml Tetrahydrofuran suspendiert und bei Raumtemperatur während 90 Minuten mit 23,6 g (0.2 Mol) Milchsäureäthylester gerüht Hierauf werden bei 60°C 9,5 g (0.18 Mol) Acrylnitril zugetropft und das Gemisch wird 90 Minuten rückflussiert. Das Reaktionsgemisch wird auf 200 ml Wasser geworfen, 2 mal mit je 100 ml Aether gewaschen, die wässerige Phase mit 2n Salzsäure auf pH 1 gestellt und 3 mal mit je 150 ml Aether extrahiert. Die getrockneten und eingeengten Aetherphasen ergeben 20,1 g (89%) 4-Cyano - 2 - methyltetrahydrofuran - 3 - on, Sdp. 116-118°/14 mm Hg: IR: 2250 (CN), 1780 (C=O); NMR (CDCl3); 1,37 ppm Dublett (CHa); 3,4―4,9 ppm Multiplett.a) 8.7 g (0.2 mol) of sodium hydride are suspended in 100 ml of tetrahydrofuran and stirred at room temperature for 90 minutes with 23.6 g (0.2 mol) of ethyl lactate. 9.5 g (0.18 mol) are then at 60 ° C. Acrylonitrile was added dropwise and the mixture was refluxed for 90 minutes. The reaction mixture is thrown onto 200 ml of water, washed twice with 100 ml of ether each time, the aqueous phase is adjusted to pH 1 with 2N hydrochloric acid and extracted three times with 150 ml of ether each time. The dried and concentrated ether phases yield 20.1 g (89%) 4-cyano-2-methyltetrahydrofuran-3-one, bp 116-118 ° / 14 mm Hg: IR: 2250 (CN), 1780 (C = O) ; NMR (CDCl 3 ); 1.37 ppm doublet (CH a ); 3.4―4.9 ppm multiplet.
  • b) Das oben erhaltene Produkt wird gemäss Beispiel 2b) behandelt. Man erhält in 71%iger Ausbeute 4 - Cyano - 4 - hydroxy - 2 - methyltetrahydrofuran - 3 - on als Diastereomerengemisch; IR: 3350 (OH); 2290 schwach (CN), 1785 und 1730 (C=N); NMR (CDCI3): 1,4-1,7 ppm Multiplett (CHa); 3,7-4,8 ppm Multiplett (3 x O-C-H), 7,1 Singulett (OH).b) The product obtained above is treated according to Example 2b). 4-Cyano-4-hydroxy-2-methyltetrahydrofuran-3-one is obtained in 71% yield as a mixture of diastereomers; IR: 3350 (OH); 2290 weak (CN), 1785 and 1730 (C = N); NMR (CDCI 3 ): 1.4-1.7 ppm multiplet (CH a ); 3.7-4.8 ppm multiplet (3 x OCH), 7.1 singlet (OH).
  • c) 3 g der erhaltenen Cyanhydrins werden zusammen mit 2,2 g Natriumacetat in 40 ml Wasser gelöst und während 15 Minuten auf 70°C erhitzt. Darauf wird 5 mal mit je 50 ml Methylenchlorid extrahiert. Die getrockneten und eingeengten Methylenchloridphasen ergeben 150 mg (6%) kristallines 4-Hydroxy-5-methyl-3(2H)-furanon, welches mit jenem in Beispiel 2c) identisch ist.c) 3 g of the cyanohydrin obtained are dissolved together with 2.2 g of sodium acetate in 40 ml of water and heated to 70 ° C. for 15 minutes. It is extracted 5 times with 50 ml of methylene chloride. The dried and concentrated methylene chloride phases yield 150 mg (6%) of crystalline 4-hydroxy-5-methyl-3 (2H) -furanone, which is identical to that in Example 2c).
Beispiel 4Example 4

  • a) 2,3 g (0,1 Mol) Natrium werden in 50 ml Isopropanol gelöst und unter Kühlung mit 14,5 g (0,11 Mol) 2-Hydroxy-buttersäure- äthylester versetzt. Bei Rückflusstemperatur werden 7,4 g (0,11 Mol) Crotonsäurenitril zugetropft und anschliessend noch 90 Minuten rückflussiert. Das Reaktionsgemisch wird auf 100 ml Wasser gegossen und bei pH 11 2 mal mit je 100 ml Methylenchlorid gewaschen. Die wässerige Phase wird mit konzentrierter Salzsäure auf pH 1 gestellt und 5 mal mit je 100 ml Methylenchlorid extrahiert. Die vereinigten organischen Phasen werden über Natriumsulfat getrocknet und eingeengt und ergeben so 10,2 g (66%) 2-Aethyl-4-cyano-5-methyltetrahydrofuran-3-on (Diastereomerengemisch) Sdp. 254°C; IR: 2370 (C=N); 1775 (C=0); MS: 153; 138; 125; 68 (100%).a) 2.3 g (0.1 mol) of sodium are dissolved in 50 ml of isopropanol and, while cooling, 14.5 g (0.11 mol) of ethyl 2-hydroxybutyrate are added. 7.4 g (0.11 mol) of crotonic acid nitrile are added dropwise at the reflux temperature and the mixture is then refluxed for a further 90 minutes. The reaction mixture is poured onto 100 ml of water and washed twice at pH 11 with 100 ml of methylene chloride. The aqueous phase is adjusted to pH 1 with concentrated hydrochloric acid and extracted 5 times with 100 ml of methylene chloride. The combined organic phases are dried over sodium sulfate and concentrated to give 10.2 g (66%) of 2-ethyl-4-cyano-5-methyltetrahydrofuran-3-one (mixture of diastereomers), bp 254 ° C .; IR: 2370 (C = N); 1775 (C = 0); MS: 153; 138; 125; 68 (100%).
  • b) 6 g des erhaltenen Nitrils werden zusammen mit 3,8 g Borax und 3,2 g Natriumhydroxyd in 40 ml Wasser gelöst und portionenweise mit 17 g Caroat versetzt. Nach 30 Minuten wird mit verdünnter Schwefelsäure (1:1) angesäuert und 4 mal mit je 50 ml Essigester extrahiert. Nach Trocknen und Einengen werden 5,5 g (83%) 2 - Aethyl - 4 - cyano - 4-hydroxy - 5 - methyl - tetrahydrofuran - 3 - on erhalten. IR: 3350 (OH), 2240 schwach (CN), 1780 und 1720 (C=0); NMR (CDCI3): 0,8-2,2 ppm Multiplett, 3,5-4,9 ppm Multiplett, 6,2 Singulett (OH).b) 6 g of the nitrile obtained are dissolved together with 3.8 g of borax and 3.2 g of sodium hydroxide in 40 ml of water and portions of 17 g of caroate are added. After 30 minutes, the mixture is acidified with dilute sulfuric acid (1: 1) and extracted 4 times with 50 ml of ethyl acetate each time. After drying and concentrating, 5.5 g (83%) of 2-ethyl-4-cyano-4-hydroxy-5-methyl-tetrahydrofuran-3-one are obtained. IR: 3350 (OH), 2240 weak (CN), 1780 and 1720 (C = 0); NMR (CDCI 3 ): 0.8-2.2 ppm multiplet, 3.5-4.9 ppm multiplet, 6.2 singlet (OH).
  • c) 5 g des erhaltenen Materials werden in 40 ml Wasser gelöst mit 2n Schwefelsäure auf pH 1 gestellt. Nach 4 stündigem Rückflussieren wird abgekühlt und hierauf 5 mal mit je 50 ml Methylenchlorid extrahiert. Die Methylenchloridphasen werden über Natriumsulfat getrocknet und eingeengt und ergeben so 2,6 g (63%) eines Gemisches von 2 - Aethyl-4 - hydroxy - 5 - methyl - 3(2H) - furanon und 5 - Aethyl - 4 - hydroxy - 2 - methyl - 3(2H)-furanon. MS: 142 (100%), 127, 114, 99, 85, 71, 57, 4. IR: 3250 (OH), 1690 (C=0), 1615 stark (C=C).c) 5 g of the material obtained are dissolved in 40 ml of water and adjusted to pH 1 with 2N sulfuric acid. After 4 hours of refluxing, the mixture is cooled and then extracted 5 times with 50 ml of methylene chloride each time. The methylene chloride phases are dried over sodium sulfate and concentrated to give 2.6 g (63%) of a mixture of 2-ethyl-4-hydroxy-5-methyl-3 (2H) -furanone and 5-ethyl-4-hydroxy-2 - methyl - 3 (2H) furanon. MS: 142 (100%), 127, 114, 99, 85, 71, 57, 4. IR: 3250 (OH), 1690 (C = 0), 1615 strong (C = C).
Beispiel 5Example 5

  • a) Werden in Beispiel 1a) anstelle des Crotonsäurenitrils 89,1 g (1,1 Mol) 2-Pentensäurenitril (hergestellt nach D. Mac Peek et. al., J. Am. Chem. Soc. 81, 680 [1959]) verwendet, erhält man in 54%iger Ausbeute 5-Aethyl - 4 - cyano - 2 - methyl - tetrahydrofuran-3-on. n20 D = 1,4552; IR: 2250 (CN), 1778 (C=0); MS: 153, 125, 96, 82 (100%).a) In Example 1a) instead of the crotonic acid nitrile, 89.1 g (1.1 mol) of 2-pentenoic acid nitrile (produced according to D. Mac Peek et. al., J. Am. Chem. Soc. 81, 680 [1959]) used, 5-ethyl-4-cyano-2-methyl-tetrahydrofuran-3-one is obtained in 54% yield. n 20 D = 1.4552; IR: 2250 (CN), 1778 (C = 0); MS: 153, 125, 96, 82 (100%).
  • b) Das erhaltene Nitril wird gemäss Beispiel 1 b) mit Caroat behandelt und ergibt in 83%iger Ausbeute zähflüssiges 5 - Aethyl - 4 - cyano-4 - hydroxy - 2 - methyltetrahydrofuran - 3 - on. n20 D = 1,4587; IR: 3400 (OH), 2240 (schwach, CN), 1785 (C=0); MS: 142 (M-HCN), 114, 97, 82, 70 (100%).b) The nitrile obtained is treated according to Example 1 b) with caroate and gives viscous 5-ethyl-4-cyano-4-hydroxy-2-methyltetrahydrofuran-3-one in 83% yield. n 20 D = 1.4587; IR: 3400 (OH), 2240 (weak, CN), 1785 (C = 0); MS: 142 (M-HCN), 114, 97, 82, 70 (100%).
  • c) Das Cyanhydrin wird gemäss Beispiel 1c) behandelt. Man erhält in 84%iger Ausbeute 5-Aethyl - 4 - hydroxy - 2 - methyl - 3(2H)-furanon. n20 D = 1,5071. Die Verbindung isomerisiert beim Stehenlassen teilweise (siehe Beispiel 4c)).c) The cyanohydrin is treated according to Example 1c). 5-Ethyl-4-hydroxy-2-methyl-3 (2H) - is obtained in 84% yield furanon. n 20 D = 1.5071. The compound partially isomerizes on standing (see Example 4c)).
Beispiel 6Example 6

  • a) Wird in Beispiel 3a) der Milchsäureäthylester durch a - Hydroxy - buttersäure- äthylester und das Acrylonitril durch 2-Pentensäurenitril (hergestellt nach D. Mac Peek et. al., J. Amer. Chem. Soc. 81, 680 [1959]) ersetzt, so erhält man neben wenig dimerem Pentensäurenitril [welches sich aus der basischen Phase abtrennen lässt] in 50%iger Ausbeute 2,5 - Diäthyl - 4 - cyanotetrahydrofuran - 3 - on. n20 D = 1,4538; IR: 2250 (CN); 1775 (C=O). NMR (CDCl3): 3,5-4,6 (M/2 Pr (H2, H5); 3,25 D und 3,08 D/1 Pr (H4); 1,4-2,1 M/4 Pr (2 x CH2); 0,8-1,3 M/6 Pr (2 x CH3); MS: 167 (M+), 139, 82 (100%).a) If the lactic acid ethyl ester in example 3a) is replaced by ethyl a - hydroxybutyrate and the acrylonitrile by 2-pentenoic acid nitrile (produced according to D. Mac Peek et. al., J. Amer. Chem. Soc. 81, 680 [1959] ) is replaced, so in addition to a little dimeric pentenonitrile [which can be separated from the basic phase], 2,5 - diethyl - 4 - cyanotetrahydrofuran - 3 - one is obtained in 50% yield. n 20 D = 1.4538; IR: 2250 (CN); 1775 (C = O). NMR (CDCl 3 ): 3.5-4.6 (M / 2 Pr (H2, H5); 3.25 D and 3.08 D / 1 Pr (H4); 1.4-2.1 M / 4 Pr (2 x CH 2 ); 0.8-1.3 M / 6 Pr (2 x CH 3 ); MS: 167 (M + ), 139, 82 (100%).
  • b) Das erhaltene Nitril wird analog Beispiel 2b) oxydiert. Man erhält in 79%iger Ausbeute zähflüssiges 2,5-Diäthyl - 4 - cyano - 4-hydroxytetrahydrofuran - 3 - on. n20 D = 1,4588; IR: 3300 (OH) 2240 (schwach, CN), 1782 (C=O); MS: 156 (M-HCN), 97, 82, 70 (100%).b) The nitrile obtained is oxidized analogously to Example 2b). Viscous 2,5-diethyl-4-cyano-4-hydroxytetrahydrofuran-3-one is obtained in 79% yield. n 20 D = 1.4588; IR: 3300 (OH) 2240 (weak, CN), 1782 (C = O); MS: 156 (M-HCN), 97, 82, 70 (100%).
  • c) Das erhaltene Cyanhydrin wird analog Beispiel 3c) gespalten. Man erhält in 75%iger Ausbeute, 2,5-Diäthyl - 4 - hydroxy - 3(2H) - furanon. Sdp. 50-55°C/0,03 mm Hg. Nach Umkristallisation aus Diisopropyläther beträgt der Schmelzpunkt 94-96°C; IR: 3250 (OH), 1690 (C=0), 1620 (C=C); NMR (CDCl3): 7,3 ppm S/1 Pr (OH), 4,37 Tr breit/1 Pr (H2), 2,65 Quart/2 Pr (CH2 an C5), 1,5-2,2 M/2 Pr (CH2 an C2), 0,8-1,4 2 x Tr/6 Pr (2 x CH3); MS: 156 (M+), 141, 99, 71, 58 (100%).c) The cyanohydrin obtained is split analogously to Example 3c). One gets in 75% yield, 2,5-diethyl - 4 - hydroxy - 3 (2H) - furanone. Bp 50-55 ° C / 0.03 mm Hg. After recrystallization from diisopropyl ether, the melting point is 94-96 ° C; IR: 3250 (OH), 1690 (C = 0), 1620 (C = C); NMR (CDCl 3 ): 7.3 ppm S / 1 Pr (OH), 4.37 Tr broad / 1 Pr (H2), 2.65 quart / 2 Pr (CH 2 at C5), 1.5-2, 2 M / 2 Pr (CH 2 at C2), 0.8-1.4 2 x Tr / 6 Pr (2 x CH 3 ); MS: 156 (M + ), 141, 99, 71, 58 (100%).
Beispiel 7Example 7

  • a) Wird in Beispiel 3a) Milchsäureäthylester durch a-Hydroxybuttersäureäthylester ersetzt, so erhält man in 68%iger Ausbeute 2 - Aethyl - 4 - cyanotetrahydrofuran - 3 - on. n20 D = 1,4641; IR: 2260 (CN), 1775 (C=O); MS: 139 (M+), 111 (M-CO), 107, 57, 54 (100%).a) If ethyl lactate is replaced by ethyl a-hydroxybutyrate in example 3a), 2-ethyl-4-cyanotetrahydrofuran-3-one is obtained in 68% yield. n 20 D = 1.4641; IR: 2260 (CN), 1775 (C = O); MS: 139 (M + ), 111 (M-CO), 107, 57, 54 (100%).
  • b) Das Nitril wird analog Beispiel 2b) oxydiert. Man erhält in 50%iger Ausbeute 2-Aethyl-4-cyano - 4 - hydroxytetrahydrofuran - 3 - on gelbes Oel. no = 1,4586, IR: 3400 (OH), 2250 (schwach, CN), 1783 (C=O); NMR (CDCl3): 4,70 ppm D/1 Pr (H5), 3,9―4,4 M/2 Pr (H2 und OH), 3,88 D/1 Pr (H5), 1,5-2,2 M/2 Pr (CH2 an C2), 1,05 Tr/3 Pr (CH3).b) The nitrile is oxidized analogously to Example 2b). 2-Ethyl-4-cyano - 4 - hydroxytetrahydrofuran - 3 - one yellow oil is obtained in 50% yield. no = 1.4586, IR: 3400 (OH), 2250 (weak, CN), 1783 (C = O); NMR (CDCl 3 ): 4.70 ppm D / 1 Pr (H5), 3.9―4.4 M / 2 Pr (H2 and OH), 3.88 D / 1 Pr (H5), 1.5- 2.2 M / 2 Pr (CH 2 at C2), 1.05 Tr / 3 Pr (CH 3 ).
  • c) Das erhaltene Cyanhydrin wird analog Beispiel 2c) behandelt. Man erhält in 41 %iger Ausbeute 5 - Aethyl - 4 - hydroxy - 3(2H) - furanon. Smp. 47-48°C (aus Diisopropyläther); IR (CHCI3): 3250 (OH), 1710 (C=O), 1620 (C=C); NMR (CDCl3): 6,4 ppm S breit/1 Pr (OH), 4,53 S/2 Pr (H2), 2,69 Quart/2 Pr (CH2 an C5), 1,27 Tr/3 Pr (CH3).c) The cyanohydrin obtained is treated analogously to Example 2c). 5-Ethyl-4-hydroxy-3 (2H) -furanone is obtained in 41% yield. Mp 47-48 ° C (from diisopropyl ether); IR (CHCI 3 ): 3250 (OH), 1710 (C = O), 1620 (C = C); NMR (CDCl 3 ): 6.4 ppm S broad / 1 Pr (OH), 4.53 S / 2 Pr (H2), 2.69 quart / 2 Pr (CH 2 at C5), 1.27 Tr / 3 Pr (CH 3 ).

Claims (14)

1. A process for the manufacture of compounds of the general formula
Figure imgb0021
wherein the radicals R are identical or different and represent a hydrogen atom or the methyl or ethyl group, which process comprises subjecting a compound of the general formula
Figure imgb0022
wherein R has the above significance, to a thermical or base catalysed cyanohydrin cleavage.
2. A process according to claim 1, wherein a compound of formula 11 is prepared by oxidising a compound of the general formula
Figure imgb0023
wherein R has the significance given in claim 1.
3. A process according to claim 2, wherein an alkali metal caroate is used as the oxidising agent.
4. A process according to claim 2 or claim 3, wherein a compound of formula III is obtained by reacting a compound of the general formula
Figure imgb0024
with a compound of the general formula
Figure imgb0025
wherein R has the significance given in claim 1 and R1 represents a lower alkyl group.
5. A process according to claim 4, wherein the reaction is carried out at an elevated temperature.
6. A process according to any one of claims 1 to 5 inclusive, wherein R represents the methyl group.
7. Compounds of the general formula
Figure imgb0026
wherein the radicals R are identical or different and represent a hydrogen atom or the methyl or ethyl group.
8. 2,5 - Dimethyl - 4 - cyano - 4 - hydroxytetrahydrofuran - 3 - one.
9. 4 - Cyano - 4 - hydroxy - 5 - methyltetrahydrofuran - 3 - one.
10. 2 - Ethyl - 4 - cyano - 4 - hydroxy - 5-methyl - tetrahydrofuran - 3 - one.
11. 4 - Cyano - 4 - hydroxy - 2 - methyltetrahydrofuran - 3 - one.
12. 5 - Ethyl - 4 - cyano - 4 - hydroxy - 2-methyl - tetrahydrofuran - 3 - one.
13. 2,5 - Diethyl - 4 - cyano - 4 - hydroxytetrahydrofuran - 3 - one.
14. 2 - Ethyl - 4 - cyano - 4 - hydroxytetrahydrofuran - 3 - one.
EP78100650A 1977-08-11 1978-08-11 Process for the preparation of furanones and intermediate products in this process Expired EP0000907B1 (en)

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US4318855A (en) * 1979-02-02 1982-03-09 Givaudan Corporation Process for the preparation of alpha-hydroxycarbonyl compounds
DE2910131A1 (en) * 1979-03-15 1980-09-25 Basf Ag PROCESS FOR THE PRODUCTION OF 2,5-DIMETHYL-4-HYDROXY-2,3-DIHYDROFURAN-3-ON
DE3070191D1 (en) * 1980-03-20 1985-03-28 Basf Ag Process for the preparation of 2,5-dimethyl-4-hydroxy-2,3-dihydrofuran-3-one and intermediates
US4294767A (en) * 1980-08-21 1981-10-13 Instituto Per La Ricerca Scientifica E Applicata Di Technologie Alimentari S.P.A Process for the preparation of 2,5-dimethyl-4-hydroxy-3(2H)-furanone and its 2,5-dialkyl homologues
DE3165294D1 (en) * 1981-01-05 1984-09-13 Istituto Per La Ricerca Scient Process for preparing 2,5-dialkyl-4-hydroxy-3(2h)-furanones and 4-alkenyl-dihydro-3(2h) furanones obtained as intermediate products
DE3367773D1 (en) * 1982-03-26 1987-01-08 Firmenich & Cie Process for preparing 4-hydroxy-2,5-dimethyl-2,3-dihydrofuran-3-one
EP0398417B1 (en) * 1989-05-18 1992-09-23 Quest International B.V. Hydroxyfuranone preparation
FR2664593B1 (en) * 1990-07-10 1992-11-06 Sanofi Sa PROCESS FOR THE PREPARATION OF DIMETHYL-2,5 HYDROXY-4 (2H) FURANONE-3.

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US3694466A (en) * 1967-06-16 1972-09-26 George H Buchi Process for the preparation of 2,5-dimethyl-4,5-dihydrofuran-3-ol-4-one
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US3887589A (en) * 1968-03-28 1975-06-03 Lever Brothers Ltd 2,5-Diethyl-4-hydroxy-2,3,-dihydrofuran-3-one
US3629393A (en) * 1969-09-11 1971-12-21 Nikken Chemicals Co Ltd Release-sustaining-tablet
US3629292A (en) * 1970-02-10 1971-12-21 Int Flavors & Fragrances Inc Process for the preparation of 2 5-dialkyl-4-hydroxy-(2h)-furan-3-ones
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US4045487A (en) * 1975-06-26 1977-08-30 Hoffmann-La Roche Inc. 1-Dimethylamino-2,4-diphenyl-1-butene-3,4-dione
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