WO2018210616A1 - Process for producing (4-halogeno-2,6-dialkylphenyl)malononitriles - Google Patents

Process for producing (4-halogeno-2,6-dialkylphenyl)malononitriles Download PDF

Info

Publication number
WO2018210616A1
WO2018210616A1 PCT/EP2018/061800 EP2018061800W WO2018210616A1 WO 2018210616 A1 WO2018210616 A1 WO 2018210616A1 EP 2018061800 W EP2018061800 W EP 2018061800W WO 2018210616 A1 WO2018210616 A1 WO 2018210616A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
palladium
malononitrile
preparation
phosphine
Prior art date
Application number
PCT/EP2018/061800
Other languages
German (de)
French (fr)
Inventor
Thomas Himmler
Christian Funke
Matthias Beller
Anahit PEWS-DAVTYAN
Helfried Neumann
Original Assignee
Bayer Cropscience Aktiengesellschaft
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Cropscience Aktiengesellschaft filed Critical Bayer Cropscience Aktiengesellschaft
Publication of WO2018210616A1 publication Critical patent/WO2018210616A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/006—Palladium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
    • C07C255/35—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups

Definitions

  • the present invention relates to a process for the preparation of (4-halo-2,6-dialkylphenyl) malononitriles of the general formula (I).
  • (4-Halogen-2,6-dialkylphenyl) malononitriles of the general formula (I) are important intermediates for the preparation of bioactive compounds which can be used especially for the control of pests in plant protection.
  • they are used for the preparation of insecticidal, acaricidal or herbicidal cyclic ketoenols (for example WO2006 / 089633), from these (4-halo-2,6-dialkylphenyl) malononitriles the corresponding (4-halo-2,6-dialkylphenyl) acetic acids and from them the (4-halo-2,6-dialkylphenyl) acetic acid chlorides are produced.
  • the present invention therefore includes a novel process for the preparation of (4-halo-2,6-dialkylphenyl) malononitriles of the formula (I)
  • R 1 and R 2 independently of one another are C 1 -C 6 -alkyl and
  • R 1 and R 2 independently of one another are C 1 -C 6 -alkyl and Hal is chlorine.
  • R 1 and R 2 are independently methyl or ethyl and Hal is chloro.
  • Suitable solvents and diluents in the preparation of the compounds of the formula (I) are, for example: nitriles, for example acetonitrile, propionitrile, butyronitrile or benzonitrile; Ethers such as, for example, methyl tert-butyl ether, cyclopentyl methyl ether, tert-amyl methyl ether, 1,2-dimethoxyethane, diethylene glycol diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane; N-substituted lactams such as N-methyl-pyrrolidone (NMP); Amides such as ⁇ , ⁇ -dimethylformamide (DMF) or ⁇ , ⁇ -dimethylacetamide (DMAC); Sulfoxides such as dimethylsulfoxide (DMSO); Sulfones such as sulfolane; or mixtures of these solvents and
  • Preferred solvents and diluents are nitriles, for example acetonitrile, propionitrile, butyronitrile or benzonitrile; N-substituted lactams such as N-methyl-pyrrolidone (NMP); Amides such as ⁇ , ⁇ -dimethylformamide (DMF) or ⁇ , ⁇ -dimethylacetamide (DMAC); Sulfoxides such as dimethylsulfoxide (DMSO); or mixtures of these solvents and diluents.
  • NMP N-substituted lactams
  • NMP N-methyl-pyrrolidone
  • Amides such as ⁇ , ⁇ -dimethylformamide (DMF) or ⁇ , ⁇ -dimethylacetamide (DMAC)
  • Sulfoxides such as dimethylsulfoxide (DMSO); or mixtures of these solvents and diluents.
  • NMP N-methyl-pyrrolidone
  • DMSO Dimethyl sulfoxide
  • DMAC ⁇ , ⁇ -dimethylacetamide
  • the base used is an alkali metal hydroxide LiOH, NaOH, KOH, RbOH or CsOH. Preference is given to using NaOH or KOH; especially preferred is NaOH.
  • the alkali metal hydroxide can be used as a solid or as an aqueous solution.
  • an aqueous solution the water must be removed from the reaction mixture, for example by distillation. Preference is therefore given to the use of the alkali metal hydroxide as a preferably water-poor solid, for example in the case of NaOH in the form of so-called microprills.
  • the amount of alkali metal hydroxide relative to malononitrile is between 1 and 5 moles per mole; preferably between 1.5 and 5 moles per mole.
  • the reaction temperature in the first step of the process according to the invention is between 50 and 200.degree. C., preferably between 75 and 150.degree.
  • the reaction water resulting from the reaction of malononitrile with the alkali metal hydroxide is removed in a second step of the process according to the invention.
  • This removal of water can be done in different ways; For example, by adding water-binding agents such as dried molecular sieve, or by distilling off the water alone or in admixture with the solvent.
  • the water is removed by distillation.
  • Particularly preferred is a Distilled off amount of solvent / W ater mixture corresponding to between 40 and 70% of the original amount of solvent.
  • Suitable palladium catalysts for the reaction of the anion of the malononitrile generated with the base with the bromoaromatic compound of the formula (II) are both palladium precatalysts in combination with suitable phosphine ligands and already preformed palladium-ligand complexes.
  • Suitable catalysts are, for example, bis (triphenylphosphine) palladium (II) chloride, bis (tri-para-tolylphosphine) palladium (II) chloride, bis (tri-para-anisylphosphine) palladium (II) chloride, tetrakis ( triphenylphosphine) palladium (0), palladium (II) chloride, palladium (II) acetate, palladium (II) nitrate, palladium (II) sulfate, palladium (II) acetylacetonate, bis (dibenzylideneacetone) palladium (O) or complex of the formula (III).
  • palladium (II) chloride palladium (II) acetate, palladium (II) nitrate, palladium (II) acetylacetonate, tetrakis (triphenylphosphine) palladium (0), bis (tri-para-anisylphosphine) palladium (II) chloride or complex of formula (III).
  • Particularly preferred are palladium (II) nitrate, palladium (II) acetylacetonate, bis (tri-para-anisylphosphine) palladium (II) chloride or complex of the formula (III).
  • Emphasized are palladium (II) nitrate, palladium (II) acetylacetonate or complex of the formula (III).
  • L is triphenylphosphine, tri (para-tolyl) phosphine or tri (para-anisyl) phosphine; preferably L is triphenylphosphine or tri (para-anisyl) phosphine; most preferably L is tri (para-anisyl) phosphine (P (p-anisyl) 3 ).
  • the palladium catalyst from a precatalyst and a phosphine ligand in particular the combinations of palladium (II) chloride, Palladium (II) acetate, palladium (II) nitrate, palladium (II) sulfate, palladium (II) acetylacetonate, bis (dibenzylideneacetone) palladium (O) or complex of the formula (III) with the phosphine ligands triphenylphosphine, tri (para -tolyl) phosphine or tri (para-anisyl) phosphine in question.
  • the molar ratios of phosphine ligand to palladium are usually in the range between 1 and 20; preferably between 1 and 10.
  • the molar ratio of malononitrile to bromoaromatic compound of the formula (II) is usually between 0.9 and 2; preferably between 1 and 1.5.
  • the reaction temperature in the third process step of the invention is between 50 and 200 ° C; preferably between 75 and 150 ° C.
  • the reaction time in the third process step is between 1 and 24 hours.
  • the entire process is preferably carried out in an inert atmosphere, this being preferably prepared by inerting with nitrogen or argon.
  • reaction mixtures The work-up of the reaction mixtures is carried out by customary and known methods of organic chemistry.
  • a mixture of 1.52 g (23 mmol) of malononitrile and 2 g (50 mmol) of NaOH (in the form of microprills) in 24 ml of DMAC is heated at 90 ° C. for 1 hour. Subsequently, about 17 ml of DMAC / water mixture are distilled off at 25-30 mbar and replaced with fresh DMAC. Thereafter, 4.39 g (20 mmol) of 4-chloro-2,6-dimethylbromobenzene, 3.05 mg (0.05 mol%) of pdacac 2 and 28.2 mg (0.4 mol%) of tri (para -anisyl) phosphine. The mixture is heated for 11 hours at 125 ° C and then analyzed by gas chromatography. The yield of the target compound is 89% of theory.
  • Example 7 (4-Chloro-2,6-dimethylphenyl) malononitrile

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The invention relates to a process for producing (4-halogeno-2,6-dialkylphenyl)malononitriles of formula (I) by reaction of bromoaromatics of formula (II) with malononitrile in the presence of a base, a palladium compound and a phosphine ligand, wherein in a first process step initially only malononitrile and the base are reacted with one another and subsequently in a second process step any water of reaction formed is distilled off together with a portion of the solvent and diluent before in the third process step the bromoaromatic of formula (II), the palladium catalyst and the phosphine ligand are added. The invention further relates to novel (4-halogeno-2,6-dialkylphenyl)malononitriles of formula (I) and to a novel palladium complex of formula (III) and to the use thereof as catalyst.

Description

Verfahren zur Herstellung von (4-Halogen-2,6-dialkylphenyl)malononitrilen  Process for the preparation of (4-halo-2,6-dialkylphenyl) malononitriles
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von (4-Halogen-2,6- dialkylphenyl)malononitrilen der allgemeinen Formel (I). The present invention relates to a process for the preparation of (4-halo-2,6-dialkylphenyl) malononitriles of the general formula (I).
(4-Halogen-2,6-dialkylphenyl)malononitrile der allgemeinen Formel (I) sind wichtige Intermediate für die Herstellung bioaktiver Verbindungen, die speziell zur Kontrolle von Schädlingen im Pflanzenschutz eingesetzt werden können. Insbesondere dienen sie zur Herstellung insektizider, akarizider oder herbizider cyclischer Ketoenole (beispielsweise WO2006/089633), wobei aus diesen (4-Halogen-2,6- dialkylphenyl)malononitrilen die entsprechenden (4-Halogen-2,6-dialkylphenyl)essigsäuren und daraus die (4-Halogen-2,6-dialkylphenyl)essigsäurechloride hergestellt werden. Es ist bereits bekannt geworden (WO2000/78712, WO2004/050607), substituierte 2,6-Dialkylphenyl- malononitrile durch Reaktion von substituierten 2,6-Dialkyl-brombenzolen mit Malononitril in Gegenwart einer Base, eines Palladiumkatalysators und eines Phosphinliganden herzustellen. Diese Methode ist jedoch nicht in allen Belangen befriedigend. Insbesondere ist nachteilig, dass relativ große Mengen an Palladiumkatalysator eingesetzt werden müssen, was das Verfahren wegen der Kosten für Palladium unökonomisch macht. Bekannt ist ein weiteres Verfahren zur Herstellung von Phenylmalononitrilen (WO 2018/015489). (4-Halogen-2,6-dialkylphenyl) malononitriles of the general formula (I) are important intermediates for the preparation of bioactive compounds which can be used especially for the control of pests in plant protection. In particular, they are used for the preparation of insecticidal, acaricidal or herbicidal cyclic ketoenols (for example WO2006 / 089633), from these (4-halo-2,6-dialkylphenyl) malononitriles the corresponding (4-halo-2,6-dialkylphenyl) acetic acids and from them the (4-halo-2,6-dialkylphenyl) acetic acid chlorides are produced. It has already become known (WO 2000/78712, WO2004 / 050607) to prepare substituted 2,6-dialkylphenyl malononitriles by reacting substituted 2,6-dialkyl bromobenzenes with malononitrile in the presence of a base, a palladium catalyst and a phosphine ligand. However, this method is not satisfactory in all respects. In particular, it is disadvantageous that relatively large amounts of palladium catalyst must be used, which makes the process uneconomical because of the cost of palladium. Another method is known for the preparation of phenylmalononitriles (WO 2018/015489).
Es besteht dementsprechend weiterhin Bedarf an einem verbesserten Verfahren zur Herstellung von (4- Halogen-2,6-dialkylphenyl)malononitrilen. Accordingly, there remains a need for an improved process for the preparation of (4-halo-2,6-dialkylphenyl) malononitriles.
Die vorliegende Erfindung beinhaltet daher ein neues Verfahren zur Herstellung von (4-Halogen-2,6- dialkylphenyl)malononitrilen der Formel (I) The present invention therefore includes a novel process for the preparation of (4-halo-2,6-dialkylphenyl) malononitriles of the formula (I)
Figure imgf000002_0001
Figure imgf000002_0001
(I) in welcher (I) in which
R1 und R2 unabhängig voneinander für Ci-Cö-Alkyl stehen und R 1 and R 2 independently of one another are C 1 -C 6 -alkyl and
Hai für Fluor oder Chlor steht, dadurch gekennzeichnet, dass ein 2,6-Dialkyl-brombenzol der Formel (II) Shark stands for fluorine or chlorine, characterized in that a 2,6-dialkylbromobenzene of the formula (II)
Figure imgf000003_0001
d l) in der die Reste R1, R2und Hai die oben angegebenen Bedeutungen haben, in Gegenwart einer Base, einer Palladiumverbindung, eines Phosphinliganden und gegebenenfalls in Gegenwart eines Lösungs- und Verdünnungsmittels mit Malononitril (CELCCNT ) umgesetzt wird, wobei in einem ersten Verfahrensschritt zunächst nur Malononitril und die Base gegebenenfalls in Gegenwart eines Lösungs- und Verdünnungsmittels miteinander umgesetzt werden und anschließend in einem zweiten Verfahrensschritt gegebenenfalls entstandenes Reaktionswasser gemeinsam mit einem Teil des Lösungs- und Verdünnungsmittels abdestilliert wird, bevor im dritten Verfahrensschritt der Bromaromat der Formel (II), der Palladiumkatalysator und der Phosphinligand hinzugegeben werden.
Figure imgf000003_0001
dl) in which the radicals R 1 , R 2 and Hal have the meanings given above, in the presence of a base, a palladium compound, a phosphine ligand and optionally in the presence of a solvent and diluent with malononitrile (CELCCNT) is reacted, wherein in a first Process step initially only malononitrile and the base are optionally reacted together in the presence of a solvent and diluent and then in a second process optionally formed water of reaction is distilled off together with a portion of the solvent and diluent before in the third step of the bromoaromatic compound of the formula (II) , the palladium catalyst and the phosphine ligand are added.
Bevorzugt ist die Herstellung von (4-Halogen-2,6-dialkylphenyl)malononitrilen der Formel (I), in welcher Preference is given to the preparation of (4-halo-2,6-dialkylphenyl) malononitriles of the formula (I) in which
R1 und R2 unabhängig voneinander für Ci-Cö-Alkyl stehen und Hai für Chlor steht. R 1 and R 2 independently of one another are C 1 -C 6 -alkyl and Hal is chlorine.
Besonders bevorzugt ist die Herstellung von (4-Halogen-2,6-dialkylphenyl)malononitrilen der Formel (I), in welcher Particularly preferred is the preparation of (4-halo-2,6-dialkylphenyl) malononitriles of the formula (I) in which
R1 und R2 unabhängig voneinander für Methyl oder Ethyl stehen und Hai für Chlor steht. R 1 and R 2 are independently methyl or ethyl and Hal is chloro.
Ganz besonders bevorzugt ist die Herstellung von Very particularly preferred is the production of
(4-Chlor-2,6-dimethylphenyl)malononitril oder (4-Chlor-2,6-diethylphenyl)malononitril. Hervorgehoben ist die Herstellung von (4-Chlor-2,6-dimethylphenyl)malononitril. Als Lösungs- und Verdünnungsmittel bei der Herstellung der Verbindungen der Formel (I) kommen beispielsweise in Frage: Nitrile wie beispielsweise Acetonitril, Propionitril, Butyronitril oder Benzonitril; Ether wie beispielsweise Methyl-tert-butyl-ether, Cyclopentyl-methyl-ether, Tert-Amyl- methylether, 1,2-Dimethoxyethan, Diethylenglykol-diethylether, Tetrahydrofuran, 2-Mefhyl- tetrahydrofuran, 1,4-Dioxan; N-substituierte Lactame wie beispielsweise N-Methyl-pyrrolidon (NMP); Amide wie beispielsweise Ν,Ν-Dimethylformamid (DMF) oder Ν,Ν-Dimethylacetamid (DMAC); Sulfoxide wie beispielsweise Dimethylsulfoxid (DMSO); Sulfone wie beispielsweise Sulfolan; oder Mischungen dieser Lösungs- und Verdünnungsmittel. (4-chloro-2,6-dimethylphenyl) malononitrile or (4-chloro-2,6-diethylphenyl) malononitrile. Emphasized is the preparation of (4-chloro-2,6-dimethylphenyl) malononitrile. Suitable solvents and diluents in the preparation of the compounds of the formula (I) are, for example: nitriles, for example acetonitrile, propionitrile, butyronitrile or benzonitrile; Ethers such as, for example, methyl tert-butyl ether, cyclopentyl methyl ether, tert-amyl methyl ether, 1,2-dimethoxyethane, diethylene glycol diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane; N-substituted lactams such as N-methyl-pyrrolidone (NMP); Amides such as Ν, Ν-dimethylformamide (DMF) or Ν, Ν-dimethylacetamide (DMAC); Sulfoxides such as dimethylsulfoxide (DMSO); Sulfones such as sulfolane; or mixtures of these solvents and diluents.
Bevorzugt als Lösungs- und Verdünnungsmittel sind Nitrile wie beispielsweise Acetonitril, Propionitril, Butyronitril oder Benzonitril; N-substituierte Lactame wie beispielsweise N-Methyl-pyrrolidon (NMP); Amide wie beispielsweise Ν,Ν-Dimethylformamid (DMF) oder Ν,Ν-Dimethylacetamid (DMAC); Sulfoxide wie beispielsweise Dimethylsulfoxid (DMSO); oder Mischungen dieser Lösungs- und Verdünnungsmittel. Preferred solvents and diluents are nitriles, for example acetonitrile, propionitrile, butyronitrile or benzonitrile; N-substituted lactams such as N-methyl-pyrrolidone (NMP); Amides such as Ν, Ν-dimethylformamide (DMF) or Ν, Ν-dimethylacetamide (DMAC); Sulfoxides such as dimethylsulfoxide (DMSO); or mixtures of these solvents and diluents.
Besonders bevorzugt als Lösungs- und Verdünnungsmittel sind N-Methyl-pyrrolidon (NMP); Dimethylsulfoxid (DMSO) oder Ν,Ν-Dimethylacetamid (DMAC). Particularly preferred solvents and diluents are N-methyl-pyrrolidone (NMP); Dimethyl sulfoxide (DMSO) or Ν, Ν-dimethylacetamide (DMAC).
Als Base wird ein Alkalihydroxid LiOH, NaOH, KOH, RbOH oder CsOH eingesetzt. Bevorzugt verwendet man NaOH oder KOH; besonders bevorzugt ist NaOH. The base used is an alkali metal hydroxide LiOH, NaOH, KOH, RbOH or CsOH. Preference is given to using NaOH or KOH; especially preferred is NaOH.
Das Alkalihydroxid kann als Feststoff oder als wässrige Lösung eingesetzt werden. Bei Einsatz einer wässrigen Lösung muß das Wasser aus dem Reaktionsgemisch entfernt werden, beispielsweise durch Destillation. Bevorzugt ist daher der Einsatz des Alkalihydroxids als möglichst wasserarmer Feststoff, beispielsweise im Fall von NaOH in Form sogenannter Microprills. The alkali metal hydroxide can be used as a solid or as an aqueous solution. When using an aqueous solution, the water must be removed from the reaction mixture, for example by distillation. Preference is therefore given to the use of the alkali metal hydroxide as a preferably water-poor solid, for example in the case of NaOH in the form of so-called microprills.
Die Menge an Alkalihydroxid bezogen auf Malononitril liegt zwischen 1 und 5 Mol pro Mol; bevorzugt zwischen 1,5 und 5 Mol pro Mol. The amount of alkali metal hydroxide relative to malononitrile is between 1 and 5 moles per mole; preferably between 1.5 and 5 moles per mole.
Die Reaktionstemperatur beim ersten Schritt des erfindungsgemäßen Verfahrens, der Umsetzung von Malononitril mit dem Alkalihydroxid, liegt zwischen 50 und 200°C, bevorzugt zwischen 75 und 150°C. The reaction temperature in the first step of the process according to the invention, the reaction of malononitrile with the alkali metal hydroxide, is between 50 and 200.degree. C., preferably between 75 and 150.degree.
Das aus der Umsetzung von Malononitril mit dem Alkalihydroxid resultierende Reaktionswasser wird in einem zweiten Schritt des erfindungsgemäßen Verfahrens entfernt. Diese Wasserentfernung kann auf verschiedene Methoden erfolgen; beispielswiese durch Zugabe wasserbindender Mittel wie getrocknetem Molekularsieb, oder durch Abdestillieren des Wasser alleine oder im Gemisch mit dem Lösungsmittel. Bevorzugt wird das Wasser durch Destillation entfernt. Besonders bevorzugt wird eine Menge an Lösungsmittel/W asser-Gemisch abdestilliert, die zwischen 40 und 70% der ursprünglichen Lösungsmittelmenge entspricht. The reaction water resulting from the reaction of malononitrile with the alkali metal hydroxide is removed in a second step of the process according to the invention. This removal of water can be done in different ways; For example, by adding water-binding agents such as dried molecular sieve, or by distilling off the water alone or in admixture with the solvent. Preferably, the water is removed by distillation. Particularly preferred is a Distilled off amount of solvent / W ater mixture corresponding to between 40 and 70% of the original amount of solvent.
Nach erfolgter Destillation kann das entfernte Lösungsmittel durch wasserfreies Lösungsmittel wieder ersetzt werden. Als Palladiumkatalysatoren für die Reaktion des mit der Base generierten Anions des Malononitrils mit dem Bromaromaten der Formel (II) kommen gleichermaßen sowohl Palladium-Präkatalysatoren in Kombination mit geeigneten Phosphinliganden als auch bereits präformierte Palladium-Ligand- Komplexe in Frage. Geeignete Katalysatoren sind beispielsweise Bis(triphenylphosphin)-palladium(II)- chlorid, Bis(tri-para-tolylphosphin)-palladium(II)-chlorid, Bis(tri-para-anisylphosphin)-palladium(II)- chlorid, Tetrakis(triphenylphosphin)palladium(0), Palladium(II)chlorid, Palladium(II)acetat, Palladium(II)nitrat, Palladium(II)sulfat, Palladium(II)acetylacetonat, Bis(dibenzylidenaceton)- palladium(O) oder Komplex der Formel (III). Bevorzugt sind Palladium(II)chlorid, Palladium(II)acetat, Palladium(II)nitrat, Palladium(II)acetylacetonat, Tetrakis(triphenylphosphin)palladium(0), Bis(tri-para- anisylphosphin)-palladium(II) -chlorid oder Komplex der Formel (III). Besonders bevorzugt sind Palladium(II)nitrat, Palladium(II)acetylacetonat, Bis(tri-para-anisylphosphin)-palladium(II)-chlorid oder Komplex der Formel (III). Hervorgehoben sind Palladium(II)nitrat, Palladium(II)acetylacetonat oder Komplex der Formel (III). After distillation, the removed solvent can be replaced by anhydrous solvent again. Suitable palladium catalysts for the reaction of the anion of the malononitrile generated with the base with the bromoaromatic compound of the formula (II) are both palladium precatalysts in combination with suitable phosphine ligands and already preformed palladium-ligand complexes. Suitable catalysts are, for example, bis (triphenylphosphine) palladium (II) chloride, bis (tri-para-tolylphosphine) palladium (II) chloride, bis (tri-para-anisylphosphine) palladium (II) chloride, tetrakis ( triphenylphosphine) palladium (0), palladium (II) chloride, palladium (II) acetate, palladium (II) nitrate, palladium (II) sulfate, palladium (II) acetylacetonate, bis (dibenzylideneacetone) palladium (O) or complex of the formula (III). Preference is given to palladium (II) chloride, palladium (II) acetate, palladium (II) nitrate, palladium (II) acetylacetonate, tetrakis (triphenylphosphine) palladium (0), bis (tri-para-anisylphosphine) palladium (II) chloride or complex of formula (III). Particularly preferred are palladium (II) nitrate, palladium (II) acetylacetonate, bis (tri-para-anisylphosphine) palladium (II) chloride or complex of the formula (III). Emphasized are palladium (II) nitrate, palladium (II) acetylacetonate or complex of the formula (III).
Der Komplex der Formel (III) hat die unten genannte Struktur: The complex of formula (III) has the structure below:
Figure imgf000005_0001
Figure imgf000005_0001
(III) wobei L für Triphenylphosphin, Tri(para-tolyl)phosphin oder Tri(para-anisyl)phosphin steht; bevorzugt steht L für Triphenylphosphin oder Tri(para-anisyl)phosphin; besonders bevorzugt steht L für Tri(para-anisyl)phosphin (P(p-Anisyl)3). (III) wherein L is triphenylphosphine, tri (para-tolyl) phosphine or tri (para-anisyl) phosphine; preferably L is triphenylphosphine or tri (para-anisyl) phosphine; most preferably L is tri (para-anisyl) phosphine (P (p-anisyl) 3 ).
Für die in-situ-Generierung des Palladiumkatalysators aus einem Präkatalysator und einem Phosphinliganden kommen insbesondere die Kombinationen von Palladium(II)chlorid, Palladium(II)acetat, Palladium(II)-nitrat, Palladium(II)sulfat, Palladium(II)acetylacetonat, Bis(di- benzylidenaceton)palladium(O) oder Komplex der Formel (III) mit den Phosphinliganden Triphenylphosphin, Tri(para-tolyl)phosphin oder Tri(para-anisyl)phosphin in Frage. Bevorzugt sind die Kombinationen von Palladium(II)chlorid, Palladium(II)acetat, Palladium(II)nitrat, Palladium(II)sulfat, Palladium(II)acetylacetonat oder Komplex der Formel (III) mit Triphenylphosphin oder Tri(para- anisyl)phosphin. Hervorgehoben sind die Kombinationen von Palladium(II)nitrat, Palladium(II)acetyl- acetonat oder Komplex der Formel (III) mit Tri(para-anisyl)phosphin. For the in-situ generation of the palladium catalyst from a precatalyst and a phosphine ligand, in particular the combinations of palladium (II) chloride, Palladium (II) acetate, palladium (II) nitrate, palladium (II) sulfate, palladium (II) acetylacetonate, bis (dibenzylideneacetone) palladium (O) or complex of the formula (III) with the phosphine ligands triphenylphosphine, tri (para -tolyl) phosphine or tri (para-anisyl) phosphine in question. Preference is given to the combinations of palladium (II) chloride, palladium (II) acetate, palladium (II) nitrate, palladium (II) sulfate, palladium (II) acetylacetonate or complex of the formula (III) with triphenylphosphine or tri (para-anisyl) phosphine. Emphasized are the combinations of palladium (II) nitrate, palladium (II) acetyl acetonate or complex of the formula (III) with tri (para-anisyl) phosphine.
Die Molverhältnisse Phosphinligand zu Palladium liegen üblicherweise im Bereich zwischen 1 und 20; bevorzugt zwischen 1 und 10. Das Molverhältnis Malononitril zu Bromaromat der Formel (II) liegt üblicherweise zwischen 0,9 und 2; bevorzugt zwischen 1 und 1,5. The molar ratios of phosphine ligand to palladium are usually in the range between 1 and 20; preferably between 1 and 10. The molar ratio of malononitrile to bromoaromatic compound of the formula (II) is usually between 0.9 and 2; preferably between 1 and 1.5.
Die Reaktionstemperatur im dritten erfindungsgemäßen Verfahrensschritt liegt zwischen 50 und 200°C; bevorzugt zwischen 75 und 150°C. The reaction temperature in the third process step of the invention is between 50 and 200 ° C; preferably between 75 and 150 ° C.
Die Reaktionszeit im dritten Verfahrensschritt liegt zwischen 1 und 24 Stunden. Das gesamte Verfahren wird bevorzugt in inerter Atmosphäre durchgeführt, wobei diese bevorzugt durch Inertisierung mit Stickstoff oder Argon hergestellt wird. The reaction time in the third process step is between 1 and 24 hours. The entire process is preferably carried out in an inert atmosphere, this being preferably prepared by inerting with nitrogen or argon.
Die Aufarbeitung der Reaktionsgemische erfolgt nach üblichen und bekannten Methoden der organischen Chemie. The work-up of the reaction mixtures is carried out by customary and known methods of organic chemistry.
Ebenfalls Gegenstand der vorliegenden Erfindung sind neue (4-Halogen-2,6-dialkylphenyl)malono- nitrile der Formel (I) Likewise provided by the present invention are novel (4-halo-2,6-dialkylphenyl) malononitriles of the formula (I)
Figure imgf000006_0001
Figure imgf000006_0001
(I) in der die Reste R1, R2und Hai die oben angegebenen Bedeutungen haben. (I) in which the radicals R 1 , R 2 and Hai have the meanings given above.
Bevorzugt sind (4-Chlor-2,6-dimethylphenyl)malononitril oder (4-Chlor-2,6-diethylphenyl)malononitril. Besonders bevorzugt ist (4-Chlor-2,6-dimethylphenyl)malononitril. Preferred are (4-chloro-2,6-dimethylphenyl) malononitrile or (4-chloro-2,6-diethylphenyl) malononitrile. Particularly preferred is (4-chloro-2,6-dimethylphenyl) malononitrile.
Ebenfalls Gegenstand der vorliegenden Erfindung ist der neue Palladiumkomplex der Formel (III) Likewise provided by the present invention is the novel palladium complex of the formula (III)
Figure imgf000007_0001
Figure imgf000007_0001
(I I I) wobei L die oben angegebenen Bedeutungen hat und seine Verwendung als Katalysator für die Umsetzung von Verbindungen der Formel (II) mit Malononitril in Gegenwart einer Base zur Herstellung von Verbindungen der Formel (I). (I I I) where L has the meanings given above and its use as a catalyst for the reaction of compounds of formula (II) with malononitrile in the presence of a base for the preparation of compounds of formula (I).
Die vorliegende Erfindung soll durch folgende Beispiele näher erläutert werden, ohne dass sie dadurch eingeschränkt werden soll. The present invention will be explained in more detail by the following examples without it being intended to limit them.
Beispiele Examples
Beispiel 1: (4-Chlor-2,6-dimethylphenyl)malononitril Example 1: (4-Chloro-2,6-dimethylphenyl) malononitrile
Figure imgf000007_0002
Figure imgf000007_0002
Man legt in einer Inertatmosphäre (Argon) 18,9 g (0,25 mol) Malononitril und 25 g (0,625 mol) NaOH (in Form von Microprills) in 400 ml Ν,Ν-Dimethylacetamid (DMAC) vor und erhitzt unter Rühren für 3 Stunden auf 90°C. Anschließend werden 157 ml DMACA asser-Gemisch bei 55 mbar abdestilliert und durch frisches DMAC ersetzt. Man erwärmt auf 125°C und gibt 54,9 g (0,25 mol) 4-Chlor-2,6-dimethyl- brombenzol, 76 mg (0,25 mmol) Palladium(II)acetylacetonat (Pdacac2) und 719 mg (2 mmol) Tri(para- anisyl)phosphin hinzu. Man rührt 16 Stunden bei 125°C unter Argon, destilliert dann bei 40 mbar 275 ml DMAC ab, kühlt auf 25°C ab und dosiert langsam so viel halbkonz. wässrige Salzsäure zu, daß der pH- Wert auf 1 fällt. Der ausgefallene Feststoff wird abfiltriert, mit Wasser gewaschen und getrocknet. Man erhält 50,73 g beigefarbenen Feststoff, der laut quant. NMR eine Reinheit von 88% besitzt, womit sich eine Ausbeute von 87% der Theorie ergibt. Schmelzpunkt: 147°C 18.9 g (0.25 mol) of malononitrile and 25 g (0.625 mol) of NaOH (in the form of microprills) in 400 ml of Ν, Ν-dimethylacetamide (DMAC) are initially charged in an inert atmosphere (argon) and the mixture is heated with stirring 3 hours at 90 ° C. Subsequently, 157 ml DMACA asser mixture are distilled off at 55 mbar and replaced with fresh DMAC. The mixture is heated to 125 ° C. and gives 54.9 g (0.25 mol) of 4-chloro-2,6-dimethylbromobenzene, 76 mg (0.25 mmol) of palladium (II) acetylacetonate (Pdacac2) and 719 mg ( 2 mmol) of tri (para-anisyl) phosphine. The mixture is stirred for 16 hours at 125 ° C under argon, then distilled at 40 mbar 275 ml of DMAC, cooled to 25 ° C and slowly added as much semicon. aqueous hydrochloric acid so that the pH drops to 1. The precipitated solid is filtered off, washed with water and dried. This gives 50.73 g of beige solid which quantified according to quant. NMR has a purity of 88%, which results in a yield of 87% of theory. Melting point: 147 ° C
GC/MS: m/e = 204 (M+, Cl35, 60%), 177 (M+-HCN, 90%), 142 (M+-HCN-C1, 100%). GC / MS: m / e = 204 (M + , Cl 35 , 60%), 177 (M + -HCN, 90%), 142 (M + -HCN-Cl, 100%).
^-NMR (600 MHz, d-DSMO): δ = 2,5 (s, 6H, 2xCH3), 6,4 (s, 1H, CH(CN)2), 7,4 (s, 2H, ArH) ppm. ^ -NMR (600 MHz, d-DMSO): δ = 2.5 (s, 6H, 2xCH 3), 6.4 (s, 1H, CH (CN) 2), 7.4 (s, 2H, ArH ) ppm.
Beispiel 2: (4-Chlor-2,6-dimethylphenyl)malononitril Example 2: (4-Chloro-2,6-dimethylphenyl) malononitrile
Eine Mischung aus 1,52 g (23 mmol) Malononitril und 2 g (50 mmol) NaOH (in Form von Microprills) in 24 ml DMAC wird für 1 Stunde auf 90°C erhitzt. Anschließend werden ca. 17 ml DMAC/Wasser- Gemisch bei 25 - 30 mbar abdestilliert und durch frisches DMAC ersetzt. Danach werden 4,39 g (20 mmol) 4-Chlor-2,6-dimethyl-brombenzol, 3,05 mg (0,05 mol%) Pdacac2 und 28,2 mg (0,4 mol%) Tri(para-anisyl)phosphin zugegeben. Das Gemisch wird für 11 Stunden auf 125°C erhitzt und anschließend gaschromatographisch analysiert. Die Ausbeute an Zielverbindung beträgt 89% der Theorie. A mixture of 1.52 g (23 mmol) of malononitrile and 2 g (50 mmol) of NaOH (in the form of microprills) in 24 ml of DMAC is heated at 90 ° C. for 1 hour. Subsequently, about 17 ml of DMAC / water mixture are distilled off at 25-30 mbar and replaced with fresh DMAC. Thereafter, 4.39 g (20 mmol) of 4-chloro-2,6-dimethylbromobenzene, 3.05 mg (0.05 mol%) of pdacac 2 and 28.2 mg (0.4 mol%) of tri (para -anisyl) phosphine. The mixture is heated for 11 hours at 125 ° C and then analyzed by gas chromatography. The yield of the target compound is 89% of theory.
Beispiel 3: (4-Chlor-2,6-dimethylphenyl)malononitril Example 3: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 2, verwendet jedoch N-Methyl-pyrrolidon (NMP) anstelle von DMAC. Ausbeute: 93% der Theorie. Beispiel 4: (4-Chlor-2,6-dimethylphenyl)malononitril  The procedure is as in Example 2, but using N-methyl-pyrrolidone (NMP) instead of DMAC. Yield: 93% of theory. Example 4: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 2, verwendet jedoch Dimethylsulfoxid (DMSO) anstelle von DMAC. Ausbeute: 99% der Theorie.  The procedure is as in Example 2, but using dimethyl sulfoxide (DMSO) instead of DMAC. Yield: 99% of theory.
Beispiel 5: (4-Chlor-2,6-dimethylphenyl)malononitril Example 5: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 2, verwendet jedoch nur 0,03 mol% Pdacac2 und 0,12 mol% Tri(para- anisyl)phosphin. Ausbeute: 37% der Theorie.  The procedure is as in Example 2, but uses only 0.03 mol% Pdacac2 and 0.12 mol% of tri (para-anisyl) phosphine. Yield: 37% of theory.
Vergleichsbeispiel 1: (4-Chlor-2,6-dimethylphenyl)malononitril Comparative Example 1: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 5, verwendet jedoch 0,12 mol% l,2-Bis(diphenylphosphino)ethan. Ausbeute: 0% der Theorie.  The procedure is as in Example 5, but using 0.12 mol% l, 2-bis (diphenylphosphino) ethane. Yield: 0% of theory.
Vergleichsbeispiel 2: (4-Chlor-2,6-dimethylphenyl)malononitril Comparative Example 2: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 5, verwendet jedoch 0,12 mol% Tri(ortho-anisyl)phosphin. Ausbeute: 0% der Theorie. The procedure is as in Example 5, but using 0.12 mol% of tri (ortho-anisyl) phosphine. Yield: 0% of theory.
Beispiel 6: (4-Chlor-2,6-dimethylphenyl)malononitril Example 6: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 2, verwendet jedoch 0,05 mol% Komplex der Formel (III) und 0,1 mol% Tri(para-anisyl)phosphin. Ausbeute: 72% der Theorie. Beispiel 7: (4-Chlor-2,6-dimethylphenyl)malononitril  The procedure is as in Example 2, but using 0.05 mol% complex of the formula (III) and 0.1 mol% of tri (para-anisyl) phosphine. Yield: 72% of theory. Example 7: (4-Chloro-2,6-dimethylphenyl) malononitrile
Man geht vor wie in Beispiel 2, verwendet jedoch 0,375 mol% Pd(N03)2-Dihydrat anstelle von Pd(acac)2 als Katalysator. Nach Rühren über Nacht bei 125°C ist nach HPLC-Analyse der Umsatz zum Zielprodukt quantitativ. The procedure is as in Example 2, but using 0.375 mol% of Pd (NO 3) 2-dihydrate instead of Pd (acac) 2 as a catalyst. After stirring overnight at 125 ° C., the conversion to the target product is quantitative according to HPLC analysis.
Beispiel 8: Komplex der Formel (III) Example 8 Complex of Formula (III)
Figure imgf000009_0001
Figure imgf000009_0001
(III) In einem 50 ml Zweihalskolben mit Rührfisch und zwei Septen werden in der Glovebox 119.04 mg (0.13mmol) Pd2(dba)3 und 183.2 mg (0.52 mmol, 2eq bezogen auf Palladium)) Tris(p- methoxyphenyl)phosphine zusammen eingewogen und mit Septen verschlossen. Nach Ausschleusen setzt man unter Argon einen Rückflusskühler auf das Reaktionsgefäß und gibt 15 ml ausgefrorenes Toluol und 60 μΐ (0.39 mmol, 1.5 eq) 4-Chlor-2,6-dimethyl-brombenzol dazu. Man stellt den Kolben mit der dunklen Suspension in ein auf 110 °C vorgeheiztes Ölbad. Die Lösung wird dunkelgelb bis schwarz. Man erhitzt das Ölbad auf 140 °C, um die Reaktionslösung zu refluxieren. Nach 10 Minuten Reflux kühlt man die Reaktionslösung ab und entfernt das Toluol im Hochvakuum. Man nimmt den schwarz-gelben Rückstand in 15 ml CH2CI2 auf und filtriert diesen über Celite. Die so erhaltene klare gelbe Lösung wird im Hochvakuum eingeengt. Mit 10 ml Diethylether wird der Rückstand gelöst und es fällt nach einiger Zeit ein gelber Niederschlag aus, der sich leicht absetzt. Man dekantiert die klare orange Lösung und wäscht 3 Mal den gelben Rückstand mit je 2 ml Diethylether. Man trocknet den Rückstand im Vakuum und man erhält einen feinen hellgelben Feststoff. Ausbeute: 120mg (45%). Laut H-NMR enthält der Komplex 7% Diethylether, der sich auch im Hochvakuum nicht entfernen lässt. (III) 119.04 mg (0.13 mmol) Pd2 (dba) 3 and 183.2 mg (0.52 mmol, 2eq based on palladium) of tris (p-methoxyphenyl) phosphines are weighed together in a glove box in a 50 ml two-necked flask with stirrer bar and two septa and closed with septa. After discharging, a reflux condenser is placed under argon on the reaction vessel and 15 ml of frozen toluene and 60 .mu.l (0.39 mmol, 1.5 eq) of 4-chloro-2,6-dimethyl-bromobenzene are added thereto. Place the flask with the dark suspension in an oil bath preheated to 110 ° C. The solution turns dark yellow to black. The oil bath is heated to 140 ° C to reflux the reaction solution. After 10 minutes of reflux, the reaction solution is cooled and the toluene is removed under high vacuum. Take the black-yellow residue in 15 ml of CH 2 Cl 2 and filtered through Celite. The resulting clear yellow solution is concentrated under high vacuum. With 10 ml of diethyl ether, the residue is dissolved and it precipitates after some time a yellow precipitate, which settles easily. Decant the clear orange solution and wash 3 times the yellow residue with 2 ml of diethyl ether. The residue is dried in vacuo and a fine pale yellow solid is obtained. Yield: 120mg (45%). According to H-NMR, the complex contains 7% diethyl ether, which can not be removed even under high vacuum.
XH-NMR (300 MHz, CD2CI2): δ = 7.42 (broad s, 12 H, CH p-anisyl), 6.79 (d, J = 8.5 Hz, 12H, CH p- anisyl), 6.09 (s, 2H, CH aryl), 3.80 (s, 18 H, OMe), 2.02 (s, 6H, Me, aryl) ppm. X H NMR (300 MHz, CD 2 Cl 2): δ = 7.42 (broad s, 12 H, CH p -anisyl), 6.79 (d, J = 8.5 Hz, 12H, CH p -anisyl), 6.09 (s, 2H, CH aryl), 3.80 (s, 18H, OMe), 2.02 (s, 6H, Me, aryl) ppm.
13C NMR (75 MHz, CD2CI2): δ = 161.3, 136.3, 125.7, 123.3, 113.6, 113.5, 113.4 (CH arom), 55.6 (OMe), 26.5 (Me) ppm. 13 C NMR (75 MHz, CD 2 Cl 2): δ = 161.3, 136.3, 125.7, 123.3, 113.6, 113.5, 113.4 (CH arom), 55.6 (OMe), 26.5 (Me) ppm.
P NMR (121 MHz, CD2C12): δ = 19.16 ppm. P NMR (121 MHz, CD 2 Cl 2 ): δ = 19.16 ppm.

Claims

Patentansprüche claims
1. Verfahren zur Herstellung von Verbindungen der Formel (I) 1. Process for the preparation of compounds of the formula (I)
Figure imgf000010_0001
in welcher R1 und R2 unabhängig voneinander für Ci-Cö-Alkyl stehen und Hai für Fluor oder Chlor steht, dadurch gekennzeichnet, dass eine Verbindung der Formel (II)
Figure imgf000010_0001
in which R 1 and R 2, independently of one another, are C 1 -C 6 -alkyl and Hal is fluorine or chlorine, characterized in that a compound of the formula (II)
Figure imgf000010_0002
in der die Reste R1, R2 und Hai die oben angegebenen Bedeutungen haben, in Gegenwart einer Base, einer Palladiumverbindung, eines Phosphinliganden und gegebenenfalls in Gegenwart eines Lösungs- und Verdünnungsmittels mit Malononitril umgesetzt wird, wobei in einem ersten Verfahrensschritt zunächst nur Malononitril und die Base miteinander umgesetzt werden und anschließend in einem zweiten Verfahrensschritt gegebenenfalls entstandenes Reaktionswasser gemeinsam mit einem Teil des Lösungs- und Verdünnungsmittels abdestilliert wird, bevor im dritten Verfahrensschritt der Bromaromat der Formel (II), der Palladiumkatalysator und der Phosphinligand hinzugegeben werden.
Figure imgf000010_0002
in which the radicals R 1 , R 2 and Hai have the meanings given above, in the presence of a base, a palladium compound, a phosphine ligand and optionally in the presence of a solvent and diluent with malononitrile, wherein in a first process step, initially only malononitrile and the base are reacted with each other and then in a second process step optionally formed reaction water is distilled off together with a portion of the solvent and diluent before the bromoaromatic compound of formula (II), the palladium catalyst and the phosphine ligand are added in the third step.
2. Verfahren zur Herstellung von Verbindungen der Formel (I) gemäß Anspruch 1, in welcher 2. A process for the preparation of compounds of formula (I) according to claim 1, in which
R1 und R2 unabhängig voneinander für Ci-Cö-Alkyl stehen und R 1 and R 2 independently of one another are C 1 -C 6 -alkyl and
Hai für Chlor steht. Shark stands for chlorine.
3. Verfahren zur Herstellung von Verbindungen der Formel (I) gemäß Anspruch 1, in welcher R1 und R2 unabhängig voneinander für Methyl oder Ethyl stehen und 3. A process for the preparation of compounds of formula (I) according to claim 1, in which R 1 and R 2 independently of one another are methyl or ethyl, and
Hai für Chlor steht. Shark stands for chlorine.
4. Verfahren zur Herstellung von (4-Chlor-2,6-dimethylphenyl)malononitril oder (4-Chlor-2,6- diethylphenyl)malononitril gemäß Anspruch 1. 4. A process for the preparation of (4-chloro-2,6-dimethylphenyl) malononitrile or (4-chloro-2,6-diethylphenyl) malononitrile according to claim 1.
5. Verfahren zur Herstellung von (4-Chlor-2,6-dimethylphenyl)malononitril gemäß Anspruch 1. 5. A process for the preparation of (4-chloro-2,6-dimethylphenyl) malononitrile according to claim 1.
6. Verfahren zur Herstellung von Verbindungen der Formel (I) gemäß Anspruch 1, wobei als Base ein Alkalihydroxid eingesetzt wird. 6. A process for the preparation of compounds of the formula (I) according to claim 1, wherein the base used is an alkali metal hydroxide.
7. Verfahren zur Herstellung von Verbindungen der Formel (I) gemäß Anspruch 1, wobei als Base NaOH eingesetzt wird. 7. A process for the preparation of compounds of formula (I) according to claim 1, wherein NaOH is used as the base.
8. Verfahren zur Herstellung von Verbindungen der Formel (I) gemäß Anspruch 1, wobei Palladium(II)nitrat, Palladium(II)acetylacetonat oder Komplex der Formel (III) 8. A process for the preparation of compounds of formula (I) according to claim 1, wherein palladium (II) nitrate, palladium (II) acetylacetonate or complex of formula (III)
L = P(p-Anisyl)3
Figure imgf000011_0001
L = P (p-anisyl) 3
Figure imgf000011_0001
(I I I) in Kombination mit Tri(para-anisyl)phosphin eingesetzt werden. (I I I) in combination with tri (para-anisyl) phosphine.
9. Verbindungen der Formel (I)
Figure imgf000012_0001
9. Compounds of the formula (I)
Figure imgf000012_0001
(I) in der die Reste R1, R2 und Hai die oben angegebenen Bedeutungen haben. (I) in which the radicals R 1 , R 2 and Hai have the meanings given above.
10. (4-Chlor-2,6-dimethylphenyl)malononitril oder (4-Chlor-2,6-diethylphenyl)malononitril 11. (4-Chlor-2,6-dimethylphenyl)malononitril 12. Palladiumkomplex der Formel (III) 10. (4-Chloro-2,6-dimethylphenyl) malononitrile or (4-chloro-2,6-diethylphenyl) malononitrile 11. (4-Chloro-2,6-dimethylphenyl) malononitrile 12. Palladium complex of the formula (III)
Figure imgf000012_0002
Figure imgf000012_0002
wobei L für Triphenylphosphin, Tri(para-tolyl)phosphin oder Tri(para-anisyl)phosphin steht. where L is triphenylphosphine, tri (para-tolyl) phosphine or tri (para-anisyl) phosphine.
Palladiumkomplex der Formel (III) gemäß Anspruch 12, wobei L für Triphenylphosphin oder Tri(para-anisyl)phosphin steht. A palladium complex of the formula (III) according to claim 12, wherein L is triphenylphosphine or tri (para-anisyl) phosphine.
14. Palladiumkomplex der Formel (III) gemäß Anspruch 12, wobei L für Tri(para-anisyl)phosphin (P(p-Anisyl)3) steht. 14. Palladium complex of formula (III) according to claim 12, wherein L is tri (para-anisyl) phosphine (P (p-anisyl) 3).
Verwendung des Palladiumkomplexes der Formel (III) gemäß Anspruch 12 als Katalysator für die Umsetzung von Verbindungen der Formel (II) mit Malononitril in Gegenwart einer Base zur Herstellung von Verbindungen der Formel (I). Use of the palladium complex of the formula (III) according to Claim 12 as catalyst for the reaction of compounds of the formula (II) with malononitrile in the presence of a base for the preparation of compounds of the formula (I).
PCT/EP2018/061800 2017-05-15 2018-05-08 Process for producing (4-halogeno-2,6-dialkylphenyl)malononitriles WO2018210616A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP17171024.7 2017-05-15
EP17171024 2017-05-15

Publications (1)

Publication Number Publication Date
WO2018210616A1 true WO2018210616A1 (en) 2018-11-22

Family

ID=58709350

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2018/061800 WO2018210616A1 (en) 2017-05-15 2018-05-08 Process for producing (4-halogeno-2,6-dialkylphenyl)malononitriles

Country Status (2)

Country Link
TW (1) TW201904936A (en)
WO (1) WO2018210616A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000078712A1 (en) 1999-06-16 2000-12-28 Syngenta Participations Ag Substituted arylmalonic acid dinitriles as intermediates for the prepartion of herbicides
WO2004050607A1 (en) 2002-12-05 2004-06-17 Syngenta Participations Ag Process for the preparation of phenylmalonic acid dinitriles
WO2006089633A2 (en) 2005-02-22 2006-08-31 Bayer Cropscience Ag Spiroketal-substituted cyclic ketoenols
WO2015161224A1 (en) * 2014-04-17 2015-10-22 Merial, Inc. Use of malononitrile compounds for protecting animals from parasites
WO2018015489A1 (en) 2016-07-22 2018-01-25 Syngenta Participations Ag Process for the preparation of phenylmalonic acid dinitriles

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000078712A1 (en) 1999-06-16 2000-12-28 Syngenta Participations Ag Substituted arylmalonic acid dinitriles as intermediates for the prepartion of herbicides
WO2004050607A1 (en) 2002-12-05 2004-06-17 Syngenta Participations Ag Process for the preparation of phenylmalonic acid dinitriles
WO2006089633A2 (en) 2005-02-22 2006-08-31 Bayer Cropscience Ag Spiroketal-substituted cyclic ketoenols
WO2015161224A1 (en) * 2014-04-17 2015-10-22 Merial, Inc. Use of malononitrile compounds for protecting animals from parasites
WO2018015489A1 (en) 2016-07-22 2018-01-25 Syngenta Participations Ag Process for the preparation of phenylmalonic acid dinitriles

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PAUL F ET AL: "structural charachterization and simple synthesis of {Pd[P(o-Tol)3]2},dimeric Palladium(II) complexes obtained by oxidative addition of aryl bromides, and corresponding monometallic amine complexes", ORGANOMETALLICS, AMERICAN CHEMICAL SOCIETY, US, vol. 14, 1 January 1995 (1995-01-01), pages 3030 - 3039, XP002358606, ISSN: 0276-7333, DOI: 10.1021/OM00006A053 *

Also Published As

Publication number Publication date
TW201904936A (en) 2019-02-01

Similar Documents

Publication Publication Date Title
EP1586563B1 (en) Preparation of thiosulphuric acid derivatives
CH649980A5 (en) PHENOXYBENZYL ALCOHOLS AND METHOD FOR THE PRODUCTION THEREOF.
DE68904558T2 (en) METHOD FOR PRODUCING BIDENTAL LIGANDS.
DE3514450A1 (en) METHOD FOR PRODUCING IMIDATES AND NEW ARYL-SUBSTITUTED IMIDATES
EP2931703B1 (en) Method for producing bis (3-aminophenyl) disulfides and 3-aminothiols
EP1077208A2 (en) Process for the preparation of (bis-(trifluormethyl)-phenyl)-acetic acids and their alkyl esters as well as dialkyl esters of (bis-(trifluormethyl)-phenyl)-malonic acid
EP1272480B1 (en) Method for the production of spirocyclic tetronic acid derivatives
WO2018210616A1 (en) Process for producing (4-halogeno-2,6-dialkylphenyl)malononitriles
DE19815323C2 (en) Process for the preparation of isochroman-3-ones
EP0056154B1 (en) Process for the preparation of 2,2-dimethyl-3-vinyl-cyclopropane-carboxylic acids and their esters
EP2729444B1 (en) Method for manufacturing 2-amino-5-cyano-n,3-dimethylbenzamide
DE4107398A1 (en) METHOD FOR PRODUCING 4-CYANO-PYRROL COMPOSITIONS SUBSTITUTED IN 3-POSITION
DE2443142C2 (en) Process for the preparation of cyclopropanecarboxylic acid nitrile
WO2017121699A1 (en) Method for the preparation of substituted 2-aryl-ethanols
EP0915840A1 (en) Process for preparing substituted valine amide derivatives
DE102009045366A1 (en) Polycyclic pentafluorosulfanylbenzene compound and process for the preparation of the compound
DD285349A5 (en) METHOD FOR PRODUCING SUBSTITUTED PYRIDYL ALKYL KETONES
EP1902042A1 (en) Process for preparing 3,4-dichloroisothiazolecarboxylic acid
DE10222330A1 (en) Non-catalytic production of alkoxybenzonitriles, useful as intermediates for the synthesis of agrochemicals and pharmaceuticals, comprises substitution of mono-halogenated starting compounds with an alcoholate
DE2263527B2 (en) 2,2-Disubstituted phenylacetonitrile derivatives, processes for their preparation and their use
EP3368510A1 (en) Method for synthesizing 2-alkyl-4-trifluoromethyl-3-alkylsulfonylbenzoic acids
EP0341478A2 (en) Method for the preparation of 2,3-dichloro-5-acetyl pyridine
EP2000458B1 (en) Method for manufacturing amines
DE19859684A1 (en) Process for the preparation of fluorine-containing phenethylamines and new, fluorine-containing beta-iminovinyl- and beta-iminoethylbenzenes
EP3497089B1 (en) Process for the preparation of 4-substituted 2,3-dihydro-1-benzofurane derivatives by cyclisation of 2-(2-diazonium-6-substituted-phenyl)ethanol salts

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18725148

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18725148

Country of ref document: EP

Kind code of ref document: A1