EP1254105A1 - Method for producing alkoxy malonic acid dinitriles - Google Patents

Method for producing alkoxy malonic acid dinitriles

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Publication number
EP1254105A1
EP1254105A1 EP01905765A EP01905765A EP1254105A1 EP 1254105 A1 EP1254105 A1 EP 1254105A1 EP 01905765 A EP01905765 A EP 01905765A EP 01905765 A EP01905765 A EP 01905765A EP 1254105 A1 EP1254105 A1 EP 1254105A1
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Prior art keywords
general formula
dehydrating agent
meaning given
acid
alkyl
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EP01905765A
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German (de)
French (fr)
Inventor
Johannes Bartek
Rudolf Fuchs
Stefan Hildbrand
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Lonza AG
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Lonza AG
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C253/00—Preparation of carboxylic acid nitriles
    • C07C253/20—Preparation of carboxylic acid nitriles by dehydration of carboxylic acid amides

Definitions

  • the invention relates to a process for the preparation of alkoxymalonitriles.
  • Anesthetic agent sevoflurane (fluoromethyl-1,1, 1,3, 3, 3 -hexafluoro-2-propyl ether) by reacting methoxymalonitrile with bromine trifluoride.
  • WO-A-98/31652 does not disclose the preparation of methoxymalonitrile.
  • the object of the present invention was therefore to provide a process for the preparation of alkoxymalonitriles.
  • R 1 is C ⁇ alkyl or halogen-substituted C ⁇ alkyl, by reaction of the corresponding alkoxymalonic acid diamides of the general formula
  • R 1 has the meaning given above, can be prepared with a dehydrating agent.
  • C 1-4 alkyl is to be understood to mean all linear or branched alkyl groups with 1-6 carbon atoms, such as, for example, methyl, ethyl,
  • BESTATIGUNGSKOPIE Propyl, isopropyl, butyl, isobutyl, .yec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, hexyl or isohexyl.
  • Halogen-substituted C 1-4 alkyl means C 1-4 alkyl groups which are substituted one or more times by halogen. Preferred halogens are fluorine, chlorine and bromine. Fluorine is particularly preferred. Examples include: mono-, di- or trifluoromethyl, chloromethyl, bromomethyl, 1- or 2-fluoroethyl, 1- or 2-chloroethyl, 1- or 2-bromoethyl and 1-, 2- or 3-fluoropropyl.
  • the radical R 1 is preferably methyl or trifluoromethyl.
  • Suitable dehydrating agents are, for example, trifluoroacetic anhydride, dibutyltin oxide, phosphorus oxychloride, phosphorus trichloride or phosphorus pentachloride. Trifluoroacetic anhydride and phosphorus oxychloride are preferred.
  • the dehydrating agent is advantageously used in amounts of 0.5 to 6 molar equivalents per amide group of the alkoxymalonic acid diamide of the formula II.
  • Suitable solvents are, for example, acetonitrile, dioxane, 1,2-dichloroethane, toluene, cyclohexane, heptane or octane. Acetonitrile is preferred.
  • the dehydration is preferably carried out in boiling solvent.
  • the dehydration is optionally carried out in the presence of a Lewis acid.
  • a Lewis acid examples are the following Lewis be mentioned as acids: BF 3, BC1 3, BBr 3, Bl 3, SbF 5, A1C1 3, AlBr 3, TiBr 4, TiCl 4, TiCl 3, ZrCl 4, PF 5, FeCl 3 and FeBr. 3
  • A1C1 3 is preferably used as Lewis acid.
  • the amount of Lewis acid is preferably 0.01 to 0.05 mol equivalent.
  • the compounds of the formula II can be prepared by known processes. So z. B. in monthly Chem., 1965, 96, 1677-1689 describes a process for the preparation of alkoxymalonic acid diamides, methyl alkoxyacetate being reacted with oxalic acid dialkyl esters and the product (dialkyl alkoxymalonic acid) being reacted with liquid ammonia.
  • R 1 has the meaning given above, is formed.
  • the 2-cyano-2-alkoxyacetamide (III) can be isolated or the dehydration reaction is allowed to proceed until the reaction product of the formula I is formed.
  • the compounds of formula III are chiral. They can therefore be in both the S configuration and the R configuration.
  • the dehydration described above produces the racemate, which can be separated into the two isomers by known processes, for example by HPLC chromatography on a chiral column stationary phase.
  • Chiral stationary phases are known and commercially available, for example from E. Merck, Waters, Daicel or Macherey & Nagel.
  • the compounds of formula III are new and also a subject of the invention.
  • the compounds of formula III can be reacted analogously to 2-cyanoacetamide, for example with 2-mercaptobenzoic acid for the preparation of 2- (4-oxobenzothiazin-2-yl) acetamide (NSuccint al., Heterocycles 1984, 22 (8 ), 1677-1682) with 1,2-diaminobenzene for the preparation of benzoimidazol-2-yl-acetonitrile (TA Fairley et al., J. Med. Chem. 1993, 36 (12), 1746-1753) or with 2-Cyanthioacetamide for the production of thiopyridines (RM Mohareb et al., Z Naturforsch. B. Anorg. Chem. Org. Chem. 1986, 41 (1), 105-109).
  • the compounds of the formula III are also suitable for the preparation of barbiturates, coumarins or vitamins analogous to the known use of 2-cyanoacetamide.

Abstract

The invention relates to a method for producing alkoxy malonic acid dinitriles of general formula (I), wherein R<1> means C1-6-alkyl or halogen-substituted C1-6-alkyl. The method is characterised in that the corresponding alkoxy malonic acid diamides of general formula (II), wherein R<1> has the aforementioned meaning, are converted by means of a dehydrating agent. The invention also relates to the intermediate products of general formula (III), whereby said products are formed during dehydration.

Description

Verfahren zur Herstellung von AlkoxymalonsäuredinitrilenProcess for the preparation of alkoxymalonitriles
Die Erfindung betrifft ein Verfahren zur Herstellung von Alkoxymalonsäuredinitrilen.The invention relates to a process for the preparation of alkoxymalonitriles.
Die internationale Patentanmeldung WO-A-98/31652 beschreibt die Herstellung desInternational patent application WO-A-98/31652 describes the preparation of the
Narkosemittels Sevofluran (Fluormethyl- 1,1, 1,3 ,3 ,3 -hexafluor-2-propy lether) durch Umsetzung von Methoxymalonsäuredinitril mit Bromtrifluorid. In WO-A-98/31652 wird jedoch nicht die Herstellung von Methoxymalonsäuredinitril offenbart.Anesthetic agent sevoflurane (fluoromethyl-1,1, 1,3, 3, 3 -hexafluoro-2-propyl ether) by reacting methoxymalonitrile with bromine trifluoride. However, WO-A-98/31652 does not disclose the preparation of methoxymalonitrile.
Aufgabe der vorliegenden Erfindung war es daher, ein Verfahren zur Herstellung von Alkoxymalonsäuredinitrilen bereitzustellen.The object of the present invention was therefore to provide a process for the preparation of alkoxymalonitriles.
Erfindungsgemäss wird diese Aufgabe durch das Verfahren nach Patentanspruch 1 gelöst.According to the invention, this object is achieved by the method according to claim 1.
Es wurde gefunden, dass Alkoxymalonsäuredinitrile der allgemeinen FormelIt has been found that alkoxymalonitriles of the general formula
worin R1 C^-Alkyl oder halogensubstituiertes C^-Alkyl bedeutet, durch Umsetzung der entsprechenden Alkoxymalonsaurediamide der allgemeinen Formelwherein R 1 is C ^ alkyl or halogen-substituted C ^ alkyl, by reaction of the corresponding alkoxymalonic acid diamides of the general formula
worin R1 die oben angegebene Bedeutung hat, mit einem Dehydratisierungsmittel hergestellt werden können.wherein R 1 has the meaning given above, can be prepared with a dehydrating agent.
Unter „C^-Alkyl" sind hier und im folgenden alle linearen oder verzweigten Alkyl- gruppen mit 1-6 Kohlenstoffatomen zu verstehen, wie beispielsweise Methyl, Ethyl,Here and below, “C 1-4 alkyl” is to be understood to mean all linear or branched alkyl groups with 1-6 carbon atoms, such as, for example, methyl, ethyl,
BESTATIGUNGSKOPIE Propyl, Isopropyl, Butyl, Isobutyl, .yec-Butyl, tert-Butyl, Pentyl, Isopentyl, tert-Pentyl, Neopentyl, Hexyl oder Isohexyl.BESTATIGUNGSKOPIE Propyl, isopropyl, butyl, isobutyl, .yec-butyl, tert-butyl, pentyl, isopentyl, tert-pentyl, neopentyl, hexyl or isohexyl.
Unter „halogensubstituiertes C^-Alkyl" sind C^-Alkylgruppen, die ein- oder mehrfach durch Halogen substituiert sind, zu verstehen. Bevorzugte Halogene sind Fluor, Chlor und Brom. Besonders bevorzugt ist Fluor. Beispielhaft seien genannt: Mono-, Di- oder Tri- fluormethyl, Chlormethyl, Brommethyl, 1- oder 2-Fluorethyl, 1- oder 2-Chlorethyl, 1- oder 2-Bromethyl und 1-, 2- oder 3-Fluorpropyl.“Halogen-substituted C 1-4 alkyl” means C 1-4 alkyl groups which are substituted one or more times by halogen. Preferred halogens are fluorine, chlorine and bromine. Fluorine is particularly preferred. Examples include: mono-, di- or trifluoromethyl, chloromethyl, bromomethyl, 1- or 2-fluoroethyl, 1- or 2-chloroethyl, 1- or 2-bromoethyl and 1-, 2- or 3-fluoropropyl.
Der Rest R1 ist vorzugsweise Methyl oder Trifluormethyl.The radical R 1 is preferably methyl or trifluoromethyl.
Geeignete Dehydratisierungsmittel sind beispielsweise Trifluoressigsäureanhydrid, Dibutylzinnoxid, Phosphoroxychlorid, Phosphortrichlorid oder Phosphorpentachlorid. Bevorzugt sind Trifluoressigsäureanhydrid und Phosphoroxychlorid.Suitable dehydrating agents are, for example, trifluoroacetic anhydride, dibutyltin oxide, phosphorus oxychloride, phosphorus trichloride or phosphorus pentachloride. Trifluoroacetic anhydride and phosphorus oxychloride are preferred.
Das Dehydratisierungsmittel wird vorteilhaft in Mengen von 0,5 bis 6 Moläquivalent pro Amidgruppe des Alkoxymalonsäurediamids der Formel II eingesetzt.The dehydrating agent is advantageously used in amounts of 0.5 to 6 molar equivalents per amide group of the alkoxymalonic acid diamide of the formula II.
Die Dehydratisierung wird vorteilhaft in einem geeigneten Lösungsmittel durchgeführt. Geeignete Lösungsmittel sind beispielsweise Acetonitril, Dioxan, 1,2-Dichlorethan, Toluol, Cyclohexan, Heptan oder Octan. Bevorzugt ist Acetonitril.The dehydration is advantageously carried out in a suitable solvent. Suitable solvents are, for example, acetonitrile, dioxane, 1,2-dichloroethane, toluene, cyclohexane, heptane or octane. Acetonitrile is preferred.
Die Dehydratisierung wird vorzugsweise in siedendem Lösungsmittel durchgeführt.The dehydration is preferably carried out in boiling solvent.
Die Dehydratisierung wird gegebenenfalls in Gegenwart einer Lewis Säure durchgeführt. Beispielhaft seien folgende Lewis Säuren genannt: BF3, BC13, BBr3, Bl3, SbF5, A1C13, AlBr3, TiBr4, TiCl4, TiCl3, ZrCl4, PF5, FeCl3 und FeBr3.The dehydration is optionally carried out in the presence of a Lewis acid. Examples are the following Lewis be mentioned as acids: BF 3, BC1 3, BBr 3, Bl 3, SbF 5, A1C1 3, AlBr 3, TiBr 4, TiCl 4, TiCl 3, ZrCl 4, PF 5, FeCl 3 and FeBr. 3
Bevorzugt wird A1C13 als Lewis-Säure eingesetzt.A1C1 3 is preferably used as Lewis acid.
Die Menge an Lewis Säure beträgt vorzugsweise 0,01 bis 0,05 Moläquivalent. Die Verbindungen der Formel II lassen sich nach bekannten Verfahren herstellen. So ist z. B. in Monatsh. Chem., 1965, 96, 1677-1689 ein Verfahren zur Herstellung von Alkoxy- malonsäurediamiden beschrieben, wobei Alkoxyessigsäuremethylester mit Oxalsäuredi- alkylestern umgesetzt werden und das Produkt (Alkoxymalonsäuredialkylester) mit flüssigem Ammoniak zur Reaktion gebracht wird.The amount of Lewis acid is preferably 0.01 to 0.05 mol equivalent. The compounds of the formula II can be prepared by known processes. So z. B. in monthly Chem., 1965, 96, 1677-1689 describes a process for the preparation of alkoxymalonic acid diamides, methyl alkoxyacetate being reacted with oxalic acid dialkyl esters and the product (dialkyl alkoxymalonic acid) being reacted with liquid ammonia.
Die erfindungsgemässe Dehydratisierung verläuft in zwei Stufen, wobei als Zwischenprodukt das entsprechende 2-Cyan-2-alkoxyacetamid der allgemeinen FormelThe dehydration according to the invention proceeds in two stages, the corresponding 2-cyano-2-alkoxyacetamide of the general formula being an intermediate
worin R1 die oben angegebene Bedeutung hat, gebildet wird.wherein R 1 has the meaning given above, is formed.
Das 2-Cyan-2-alkoxyacetamid (III) kann isoliert werden oder man lässt die De- hydratisierungsreaktion fortschreiten, bis das Reaktionsprodukt der Formel I entstanden ist.The 2-cyano-2-alkoxyacetamide (III) can be isolated or the dehydration reaction is allowed to proceed until the reaction product of the formula I is formed.
Zur Isolierung der 2-Cyan-2-alkoxyacetamide (III) wird der Verlauf der Dehydratisierungs- reaktion verfolgt, beispielsweise mittels Dünnschichtchromatographie. Die Reaktion wird im geeigneten Zeitpunkt gestoppt, beispielsweise durch Abkühlen der siedenden Reaktionsmischung auf 50-0 °C, vorzugsweise auf circa 0°C.To isolate the 2-cyano-2-alkoxyacetamides (III), the course of the dehydration reaction is followed, for example by means of thin layer chromatography. The reaction is stopped at the appropriate point in time, for example by cooling the boiling reaction mixture to 50-0.degree. C., preferably to about 0.degree.
Die Aufarbeitung erfolgt nach bekannten Methoden, beispielsweise mittels Extraktion in Gegenwart einer Base und anschliessende Chromatographie. Als Base eignet sich beispielsweise Natriumhydrogencarbonat.Working up is carried out according to known methods, for example by extraction in the presence of a base and subsequent chromatography. Sodium hydrogen carbonate, for example, is suitable as the base.
Die Verbindungen der Formel III sind chiral. Sie können somit sowohl in S-Konfiguration als auch in R-Konfiguration vorliegen. Bei der oben beschriebenen Dehydratisierung entsteht das Racemat, welches nach bekannten Verfahren in die beiden Isomere aufgetrennt werden kann, beispielsweise durch HPLC Chromatographie über eine Säule mit chiraler stationärer Phase. Chirale stationäre Phasen sind bekannt und im Handel erhältlich, beispielsweise bei den Firmen E. Merck, Waters, Daicel oder Macherey & Nagel.The compounds of formula III are chiral. They can therefore be in both the S configuration and the R configuration. The dehydration described above produces the racemate, which can be separated into the two isomers by known processes, for example by HPLC chromatography on a chiral column stationary phase. Chiral stationary phases are known and commercially available, for example from E. Merck, Waters, Daicel or Macherey & Nagel.
Die Verbindungen der Formel III sind neu und ebenfalls Gegenstand der Erfindung.The compounds of formula III are new and also a subject of the invention.
Die Verbindungen der Formel III lassen sich analog zu 2-Cyanacetamid umsetzen, beispielsweise mit 2-Mercaptobenzoesäure zur Herstellung von 2-(4-Oxo-benzothiazin-2-yl)- acetamid (N. S. Ibrahim et al., Heterocycles 1984, 22(8), 1677-1682) mit 1,2-Di- aminobenzol zur Herstellung von Benzoimidazol-2-yl-acetonitril (T. A. Fairley et al., J. Med. Chem. 1993, 36(12), 1746-1753) oder mit 2-Cyanthioacetamid zur Herstellung von Thiopyridinen (R. M. Mohareb et al., Z Naturforsch. B. Anorg. Chem. Org. Chem. 1986, 41(1), 105-109). Ebenso eignen sich die Verbindungen der Formel III zur Herstellung von Barbituraten, Cumarinen oder Vitaminen analog zur bekannten Verwendung von 2-Cyanacetamid.The compounds of formula III can be reacted analogously to 2-cyanoacetamide, for example with 2-mercaptobenzoic acid for the preparation of 2- (4-oxobenzothiazin-2-yl) acetamide (NS Ibrahim et al., Heterocycles 1984, 22 (8 ), 1677-1682) with 1,2-diaminobenzene for the preparation of benzoimidazol-2-yl-acetonitrile (TA Fairley et al., J. Med. Chem. 1993, 36 (12), 1746-1753) or with 2-Cyanthioacetamide for the production of thiopyridines (RM Mohareb et al., Z Naturforsch. B. Anorg. Chem. Org. Chem. 1986, 41 (1), 105-109). The compounds of the formula III are also suitable for the preparation of barbiturates, coumarins or vitamins analogous to the known use of 2-cyanoacetamide.
Die folgenden Beispiele erläutern das erfindungsgemässe Verfahren.The following examples illustrate the process according to the invention.
Beispiel 1 Herstellung von Methoxymalonsäuredinitril in Gegenwart von POCI3 Example 1 Preparation of methoxymalonitrile in the presence of POCI 3
Zu einer Lösung von 10,0 g (75,7 mmol) Methoxymalonsäurediamid in 50 ml Acetonitril wurden 13,62 g (87,0 mmol) POCl3 und 0,3 g (2,3 mmol) A1C13 gegeben und das Reaktionsgemisch wurde 4 h unter Rückfluss erhitzt. Das Lösungsmittel wurde abdestilliert, Wasser wurde zugegeben und die wässrige Phase wurde mit Diethylether (3x50 ml) extrahiert. Die organische Phase wurde getrocknet und das Lösungsmittel am Rotationsverdampfer abgezogen. Reinigung des Rückstands (7,28 g) mittels Kugelrohrdestillation (110 °C/20 mbar) lieferte 4,42 g (61%) Methoxymalonsäuredinitril als farblose Flüssigkeit. Η NMR (CDC13): δ = 5,26 (s, 1H); 3,65 (s, 3H). 13C NMR (CDClj): δ = 110,12 (C≡N); 57,58 (CH3); 57,33 (CH). Beispiel 2To a solution of 10.0 g (75.7 mmol) methoxymalonic acid diamide in 50 ml acetonitrile, 13.62 g (87.0 mmol) POCl 3 and 0.3 g (2.3 mmol) A1C1 3 were added and the reaction mixture was Heated under reflux for 4 h. The solvent was distilled off, water was added and the aqueous phase was extracted with diethyl ether (3x50 ml). The organic phase was dried and the solvent was removed on a rotary evaporator. Purification of the residue (7.28 g) using Kugelrohr distillation (110 ° C / 20 mbar) gave 4.42 g (61%) methoxymalonitrile as a colorless liquid. Η NMR (CDC1 3 ): δ = 5.26 (s, 1H); 3.65 (s, 3H). 13 C NMR (CDClj): δ = 110.12 (C≡N); 57.58 (CH 3 ); 57.33 (CH). Example 2
Herstellung von Methoxymalonsäuredinitril in Gegenwart von TrifluoressigsäureanhydridPreparation of methoxymalonitrile in the presence of trifluoroacetic anhydride
In einem 3 -Halsrundkolben von 250 ml wurden unter Argon 10 g (75,7 mmol) Methoxy- malonsäurediamid, 22 g (278 mmol) Pyridin und 100 ml Dioxan vorgelegt. Bei 2-5 °C wurden 48,3 g (230 mmol) Trifluoressigsäureanhydrid zugetropft. Man liess das Reaktionsgemisch 24 h bei Raumtemperatur reagieren. Danach wurden bei 10 °C 200 ml Wasser und anschliessend 200 ml Methylenchlorid zugegeben. Nach der Phasentrennung wurde noch einmal mit 200 ml Methylenchlorid extrahiert. Die vereinten organischen Phasen wurden eingeengt, und das so erhaltene ölige Rohprodukt (7 g) wurde destilliert. (27-30 °C/1, 6 mbar). Ausbeute: 2,6 g; 33%10 g (75.7 mmol) of methoxymalonic acid diamide, 22 g (278 mmol) of pyridine and 100 ml of dioxane were placed in a 3-necked round bottom flask of 250 ml under argon. 48.3 g (230 mmol) of trifluoroacetic anhydride were added dropwise at 2-5 ° C. The reaction mixture was allowed to react at room temperature for 24 hours. Then 200 ml of water and then 200 ml of methylene chloride were added at 10 ° C. After phase separation, the mixture was extracted again with 200 ml of methylene chloride. The combined organic phases were concentrated and the resulting oily crude product (7 g) was distilled. (27-30 ° C / 1.6 mbar). Yield: 2.6 g; 33%
Beispiel 3 2-Cyan-2-methoxy-acetamidExample 3 2-Cyan-2-methoxy-acetamide
Zu einer Lösung von 5,0 g (38 mmol) Methoxymalonsäurediamid in 100 ml Acetonitril wurden bei Raumtemperatur 6,74 g (44 mmol) POCl3 und 152 mg (1,14 mmol) A1C13 gegeben. Diese Mischung wurde anschliessend unter Rückfluss zum Sieden erhitzt. Der Verlauf der Reaktion wurde mittels DC verfolgt (Laufmittel: Ethylacetat/Hexan 1/1; R des Produkts: 0,24). Nach 2,5 h wurde das Reaktionsgemisch auf 0 °C abgekühlt und vorsichtig unter Rühren auf 100 ml gesättigte Natriumhydrogencarbonatlösung gegossen. Diese Mischung wurde dann 5 mal mit je 100 ml Ethylacetat extrahiert. Die vereinigten organischen Phasen wurden über Na2SO4 getrocknet und eingedampft. Eine anschliessende Flash-Chromatographie über Kieselgel Si60 (Säule 25x5,5 cm; Hexan/Ethylacetat 3/1) ergab 3,5 g (81%) 2-Cyan-2-methoxy-acetamid als farblose Flüssigkeit, die bei Kühlung erstarrte. 'H NMR (CDC13): δ = 6,85 (bs, 1H); 6,65 (bs, 1H); 4,65 (s, 1H); 3,63 (s, 3H).At room temperature, 6.74 g (44 mmol) of POCl 3 and 152 mg (1.14 mmol) of A1C1 3 were added to a solution of 5.0 g (38 mmol) of methoxymalonic acid diamide in 100 ml of acetonitrile. This mixture was then heated to boiling under reflux. The course of the reaction was monitored by TLC (eluent: ethyl acetate / hexane 1/1; R of the product: 0.24). After 2.5 h the reaction mixture was cooled to 0 ° C. and carefully poured onto 100 ml of saturated sodium bicarbonate solution with stirring. This mixture was then extracted 5 times with 100 ml of ethyl acetate each time. The combined organic phases were dried over Na 2 SO 4 and evaporated. A subsequent flash chromatography on silica gel Si60 (column 25 × 5.5 cm; hexane / ethyl acetate 3/1) gave 3.5 g (81%) of 2-cyano-2-methoxyacetamide as a colorless liquid which solidified on cooling. 'H NMR (CDC1 3 ): δ = 6.85 (bs, 1H); 6.65 (bs, 1H); 4.65 (s, 1H); 3.63 (s, 3H).
13C NMR (CDCI3): δ = 165,2 (C=O); 114,2 (C≡N); 70,6(CH); 58,7 (CH3). 13 C NMR (CDCI 3 ): δ = 165.2 (C = O); 114.2 (C≡N); 70.6 (CH); 58.7 (CH 3 ).

Claims

Patentansprüche claims
1. Verfahren zur Herstellung von Alkoxymalonsäuredinitrilen der allgemeinen Formel1. Process for the preparation of alkoxymalonitriles of the general formula
worin R1 C^-Alkyl oder halogensubstituiertes C,^-Alkyl bedeutet, dadurch gekennzeichnet, dass die entsprechenden Alkoxymalonsaurediamide der allgemeinen Formelwherein R 1 is C ^ alkyl or halogen-substituted C, ^ - alkyl, characterized in that the corresponding alkoxymalonic acid diamides of the general formula
worin R1 die oben angegebene Bedeutung hat, mit einem Dehydratisierungsmittel umgesetzt werden.wherein R 1 has the meaning given above, are reacted with a dehydrating agent.
2. Verfahren zur Herstellung von 2-Cyan-2-alkoxyacetamiden der Formel2. Process for the preparation of 2-cyano-2-alkoxyacetamides of the formula
worin R1 die in Anspruch 1 angegebene Bedeutung hat, dadurch gekennzeichnet, dass die entsprechenden Alkoxymalonsaurediamide der allgemeinen Formelwherein R 1 has the meaning given in claim 1, characterized in that the corresponding alkoxymalonic acid diamides of the general formula
worin R1 die in Anspruch 1 angegebene Bedeutung hat, mit einem Dehydratisierungsmittel umgesetzt werden und die Reaktion gestoppt wird, bevor die weitere Umsetzung zu 2-Cyan-2-alkoxyacetamiden (I) erfolgt. wherein R 1 has the meaning given in claim 1, are reacted with a dehydrating agent and the reaction is stopped before the further conversion to 2-cyano-2-alkoxyacetamides (I).
3. Verfahren gemäss Anspruch 2, dadurch gekennzeichnet, dass die Reaktion durch Abkühlen der Reaktionsmischung auf 50-0 °C gestoppt wird.3. The method according to claim 2, characterized in that the reaction is stopped by cooling the reaction mixture to 50-0 ° C.
4. Verfahren gemäss einem der Ansprüche 1 bis 3, dadurch gekennzeichnet, dass als Dehydratisierungsmittel Trifluoressigsäureanhydrid, Dibutylzinnoxid, Phosphoroxy- chlorid, Phosphortrichlorid oder Phosphorpentachlorid eingesetzt wird.4. The method according to any one of claims 1 to 3, characterized in that trifluoroacetic anhydride, dibutyltin oxide, phosphorus oxychloride, phosphorus trichloride or phosphorus pentachloride is used as the dehydrating agent.
5. Verfahren gemäss Anspruch 4, dadurch gekennzeichnet, dass das Dehydratisierungsmittel in Mengen von 0,5 bis 6 Moläquivalent pro Amidgruppe des Alkoxymalonsäure- diamids (II) eingesetzt wird.5. The method according to claim 4, characterized in that the dehydrating agent is used in amounts of 0.5 to 6 molar equivalents per amide group of the alkoxymalonic acid diamide (II).
6. Verfahren gemäss einem der Ansprüche 1 bis 5, dadurch gekennzeichnet, dass die Dehydratisierung in einem siedenden Lösungsmittel durchgeführt wird.6. The method according to any one of claims 1 to 5, characterized in that the dehydration is carried out in a boiling solvent.
7. Verfahren gemäss einem der Ansprüche 1 bis 6, dadurch gekennzeichnet, dass die Dehydratisierung in Gegenwart einer Lewis Säure erfolgt.7. The method according to any one of claims 1 to 6, characterized in that the dehydration takes place in the presence of a Lewis acid.
8. Verfahren gemäss Anspruch 7, dadurch gekennzeichnet, dass als Lewis Säure A1C13 eingesetzt wird.8. The method according to claim 7, characterized in that A1C1 3 is used as Lewis acid.
9. Verfahren gemäss einem der Ansprüche 1 bis 8, dadurch gekennzeichnet, dass R1 Methyl oder Trifluormethyl bedeutet. Verbindungen der allgemeinen Formel9. The method according to any one of claims 1 to 8, characterized in that R 1 is methyl or trifluoromethyl. Compounds of the general formula
worin R1 die in Anspruch 1 angegebene Bedeutung hat. wherein R 1 has the meaning given in claim 1.
EP01905765A 2000-02-10 2001-02-09 Method for producing alkoxy malonic acid dinitriles Withdrawn EP1254105A1 (en)

Priority Applications (1)

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EP01905765A EP1254105A1 (en) 2000-02-10 2001-02-09 Method for producing alkoxy malonic acid dinitriles

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
EP00102758 2000-02-10
EP00102758 2000-02-10
EP00109505 2000-05-04
EP00109505 2000-05-04
US26708701P 2001-02-07 2001-02-07
US267087P 2001-02-07
EP01905765A EP1254105A1 (en) 2000-02-10 2001-02-09 Method for producing alkoxy malonic acid dinitriles
PCT/EP2001/001505 WO2001058857A1 (en) 2000-02-10 2001-02-09 Method for producing alkoxy malonic acid dinitriles

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US20030144538A1 (en) 2003-07-31
US6673957B2 (en) 2004-01-06

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