EP2318569A1 - Method for anodic dehydrodimerisation of substituted arylalcohols - Google Patents

Method for anodic dehydrodimerisation of substituted arylalcohols

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Publication number
EP2318569A1
EP2318569A1 EP09782303A EP09782303A EP2318569A1 EP 2318569 A1 EP2318569 A1 EP 2318569A1 EP 09782303 A EP09782303 A EP 09782303A EP 09782303 A EP09782303 A EP 09782303A EP 2318569 A1 EP2318569 A1 EP 2318569A1
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EP
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Prior art keywords
alcohols
alkyl
electrolysis
mediators
aryl
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EP09782303A
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German (de)
French (fr)
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EP2318569B1 (en
Inventor
Andreas Fischer
Itamar Michael Malkowsky
Florian Stecker
Siegfried Waldvogel
Axel Kirste
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BASF SE
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BASF SE
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    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
    • C25B3/20—Processes
    • C25B3/23—Oxidation
    • C—CHEMISTRY; METALLURGY
    • C25—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES; APPARATUS THEREFOR
    • C25B—ELECTROLYTIC OR ELECTROPHORETIC PROCESSES FOR THE PRODUCTION OF COMPOUNDS OR NON-METALS; APPARATUS THEREFOR
    • C25B3/00—Electrolytic production of organic compounds
    • C25B3/20—Processes
    • C25B3/29—Coupling reactions

Definitions

  • the invention relates to a process for the preparation of biaryl alcohols, which is carried out by anodic dehydrodimerization of substituted phenols in the presence of partially and / or perfluorinated mediators and a conductive salt on a graphite electrode.
  • the method according to the invention makes it possible to use very inexpensive electrode materials, undivided cell structures and solvent-free methods.
  • mediators e.g. 1, 1, 1, 3,3,3-hexafluoroisopropanol or the much cheaper trifluoroacetic acid are used.
  • the workup and recovery of the desired biphenols is very simple.
  • Biaryls are known as such and are industrially produced and used. Compounds of this class of compounds are i.a. as backbones for ligands of great interest for stereoselective transformations.
  • One possible approach to this class of substance is the electrochemical oxidative dimerization of phenols, which, however, is nonselective in electrolytes known to those skilled in the art.
  • iron (III) salts or other strong oxidizing agents are used as an alternative to the electrochemical dimerization of phenols.
  • Particularly favored and therefore frequently used substrates have annellated benzene rings or sterically demanding alkyl groups.
  • the 2,2'-dihydroxy-1,1'-binaphthyl (BINOL) prepared from 2-naphthol can be used here.
  • the main product is usually not the desired ortho, ortho-linked product 2 but a derivative of the Pummerer ketone (3).
  • the formation of the tricyclic skeleton 3 is known for para-alkyl-substituted phenols and is also found in the synthesis of many natural products.
  • BDD boron-doped diamond electrodes
  • the object of the present invention is to provide a method with which the selective and efficient oxidative coupling of substituted phenols takes place without having to work in the presence of expensive electrode material.
  • the coupling of substituted phenols should take place in the ortho position.
  • This object is achieved by a process for the preparation of biaryl alcohols, wherein substituted aryl alcohols are anodically dehydro-dimerized in the presence of partially and / or perfluorinated mediators and at least one conducting salt with the aid of a graphite electrode.
  • the process according to the invention is advantageous if the OH group of the substituted aryl alcohols used is seated directly on the aromatic compound.
  • the process according to the invention is advantageous if the substituted aryl alcohols used are identical.
  • the process according to the invention is advantageous if the substituted aryl alcohols used can be mononuclear or polynuclear.
  • the process according to the invention is advantageous if the dimerization takes place ortho to the alcohol group of the substituted aryl alcohols.
  • the process according to the invention is advantageous if the mediators used are partially and / or perfluorinated alcohols and / or acids.
  • the process according to the invention is advantageous if the mediators used are 1, 1, 1, 3,3,3-hexafluoroisopropanol or trifluoroacetic acid.
  • the process according to the invention is advantageous if the conductive salts used are those selected from the group consisting of alkali metal, alkaline earth metal, tetra (C 1 to C 6 alkyl) ammonium salts.
  • the counterions of the conducting salts are selected from the group consisting of sulfate, hydrogensulfate, alkyl sulfates, aryl sulfates, halides, phosphates, carbonates, alkyl phosphates, alkyl carbonates, nitrate, alcoholates, tetrafluoroborate, hexafluorophosphate and perchlorate.
  • the process according to the invention is advantageous if no further solvent is used for the electrolysis.
  • the process according to the invention is advantageous if a flow cell is used for the electrolysis.
  • the process according to the invention is advantageous when current densities of 1 to 1000 mA / cm 2 are used.
  • the process according to the invention is advantageous if the electrolysis is carried out at temperatures in the range from -20 to 60 ° C. and normal pressure.
  • the process according to the invention is advantageous if 2,4-dimethylphenol is used as the aryl alcohol.
  • aryl alcohol is understood as meaning aromatic alcohols in which the hydroxyl group is bonded directly to the aromatic nucleus.
  • the aromatic which is based on the aryl alcohol, may be mononuclear or polynuclear.
  • the aromatic is preferably mononuclear (phenol derivatives) or binuclear (naphthol derivatives), in particular mononuclear.
  • the aryl alcohols may also carry further substituents.
  • substituents are independently selected from the group of C 1 -C 10 -alkyl groups, halogens, C 1 -C 10 -alkoxy groups, alkylene or arylene radicals interrupted by oxygen or sulfur, C 1 -C 10 -alkoxycarboxyl, nitrile, nitro and C 1 -C 10 -alkoxycarbamoyl, particularly preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, trifluoromethyl, fluorine, chlorine, bromine, iodine, methoxy, ethoxy, methylene, ethylene, propylene, isopropylene, benzylidene, nitrile, nitro, very particularly preferably methyl, Me - thoxy, methylene, ethylene, trifluoromethyl, fluorine and bromine.
  • aryl alcohols can be used.
  • electron-rich arenes such as phenol and mono- or polysubstituted phenols and naphthol ( ⁇ - and ß-) and substituted derivatives thereof, very particularly preferred are phenols, and particularly particularly preferred are 4-alkyl and 2,4-dialkyl-substituted phenols.
  • Suitable substrates for the electrodimerization according to the present invention are in principle all aryl alcohols, provided that they are capable of dimerization due to their spatial structure and steric requirements.
  • the aryl alcohols may be mononuclear, dinuclear, trinuclear or higher nuclear. Preferably, they are mononuclear or dinuclear, in particular mononuclear.
  • the aryl alcohols preferably have an OH function.
  • Suitable aryl alcohols include phenol and mono- and polysubstituted substituted phenols represented by the following formula (I) wherein R1 to R4 are independently the same or different and are selected from the following substituents: H, Ci-Cio-alkyl , C 1 -C 10 -alkoxy, halogen, C 1 -C 10 -alkoxycarboxyl, nitrile and also mono- and di-C 1 -C 10 -alkoxycarbamoyl.
  • R1 to R4 are independently the same or different and are selected from the following substituents: H, Ci-Cio-alkyl , C 1 -C 10 -alkoxy, halogen, C 1 -C 10 -alkoxycarboxyl, nitrile and also mono- and di-C 1 -C 10 -alkoxycarbamoyl.
  • naphthol ⁇ - and ⁇ -
  • substituted derivatives thereof according to the following formulas (II) and (III), in which the radicals R 1 to R 7, identical or different and selected from the following substituents: H, Ci-Cio Alkyl, Ci-Cio-Alkoxy, halogen, Ci-Cio-Alkoxycarboxyl, nitrile as well as mono- and di-C1-C10-Alkoxycarbamoyl.
  • the electrolyte solution is worked up by general separation methods.
  • the electrolyte solution is generally first distilled and recovered the individual compounds in the form of different fractions separately. Further purification can be carried out, for example, by crystallization, distillation, sublimation or chromatographic.
  • the preparation of the biaryl alcohol is carried out electrolytically, with the corresponding aryl alcohol being oxidized anodically.
  • the process according to the invention is referred to below as electrodimerization. It has surprisingly been found that arise by the process according to the invention using mediators, the biaryl alcohols selectively and in high yield. Furthermore, it has been found that very inexpensive electrode materials, undivided cell structures and solvent-free methods can be used by the method according to the invention.
  • the workup and recovery of the desired biphenols is very simple.
  • the electrolyte solution is worked up by general separation methods. For this purpose, the electrolyte solution is generally first distilled and recovered the individual compounds in the form of different fractions separately.
  • Further purification can be carried out, for example, by crystallization, distillation, sublimation or chromatographic.
  • Partially and / or perfluorinated alcohols and / or acids preferably perfluorinated alcohols and carboxylic acids, very particularly preferably 1, 1, 1, 3, 3, 3-hexafluoroisopropanol or trifluoroacetic acid are used as mediators in the process according to the invention. No additional solvents are required in the electrolyte.
  • electrolysis is carried out in the usual, known in the art electrolysis cells. Suitable electrolysis cells are known to the person skilled in the art. Preferably, one works continuously in undivided flow cells or discontinuously in beaker cells.
  • bipolar switched capillary gap cells or Plattenstapelzellen, in which the electrodes are designed as plates and are arranged plane-parallel as in Ullmann's Encyclopedia of Industrial Chemistry, 1999 electronic release, Sixth Edition, VCH-Weinheim, Volumne and in Electrochemistry , Chapter 3.5. special cell designs as well as Chapter 5, Organic Electrochemistry, Subchapter 5.4.3.2 Cell Design.
  • the current densities at which the process is carried out are generally 1 to 1000, preferably 5 to 100 mA / cm 2 .
  • the temperatures are usually from -20 to 60 ° C., preferably from 10 to 60 ° C.
  • the reaction is generally carried out under atmospheric pressure. Higher pressures are preferably used when operating at higher temperatures to avoid boiling of the co-solvents or mediators.
  • Suitable anode materials are, for example, noble metals such as platinum or metal oxides such as ruthenium or chromium oxide or mixed oxides of the type RuO x TiO x and diamond electrodes. Preference is given to graphite or carbon electrodes.
  • the cathode material for example, iron, steel, stainless steel, nickel or E- delmetalle such as platinum and graphite or carbon materials and diamond electrodes into consideration.
  • the system is preferably graphite as the anode and cathode, graphite as the anode and nickel, stainless steel or steel as the cathode and platinum as the anode and cathode.
  • the aryl alcohol compound is dissolved in a suitable solvent.
  • a suitable solvent preferably solvents from the group of polar protic and polar aprotic solvents, are suitable.
  • the aryl alcohol compound itself serves as a solvent and reagent.
  • polar aprotic solvents examples include nitriles, amides, carbonates, ethers, ureas, chlorinated hydrocarbons.
  • polar aprotic solvents examples include Actonitrile, dimethylformamide, dimethyl sulfoxide, propylene carbonate and dichloromethane.
  • polar protic solvents examples include alcohols, carboxylic acids and amides.
  • polar protic solvents examples include methanol, ethanol, propanol, butanol, pentanol and hexanol. These may also be partially or completely halogenated, e.g. 1, 1, 1, 3,3,3-hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA).
  • HFIP 1, 1, 1, 3,3,3-hexafluoroisopropanol
  • TFA trifluoroacetic acid
  • the electrolysis solution is added to customary cosolvents.
  • these are the inert solvents customary in organic chemistry and have a high oxidation potential. Examples include its dimethyl carbonate, propylene carbonate, tetrahydrofuran, dimethoxyethane, acetonitrile or dimethylformamide.
  • Conducting salts which are contained in the electrolysis solution are generally alkali metal, alkaline earth metal, tetra (C 1 -C 6 -alkyl) ammonium, preferably tri (cis-bisalkyl) -methylammonium salts.
  • Suitable counterions are sulfate, bisulfate, alkyl sulfates, aryl sulfates, halides, phosphates, carbonates, alkyl phosphates, alkyl carbonates, nitrate, alcoholates, tetrafluoroborate, hexafluorophosphate or perchlorate.
  • the acids derived from the abovementioned anions are suitable as conductive salts.
  • MTBS methyltributylammonium methylsulfates
  • MTES methyltriethylammonium methylsulfate
  • TABF tetrabutylammonium, tetrafluoroborate
  • TFA trifluoroacetic acid
  • AcOH acetic acid
  • Phenol 2,4-dimethylphenol
  • MTES methyltriethylammonium methyl sulfate
  • Phenol 2-bromo-4-methylphenol
  • a N, N-dimethylpyrrolidinium methylsulfate
  • b yield considering the recovered phenol
  • c isolation by crystallization from toluene and chromatographic
  • d isolation by crystallization from 'PrOH: water and chromatographic.
  • Example 1 Anodic oxidation of 2,4-dimethylphenol on graphite electrodes with trifluoroacetic acid
  • the solvent is first removed and then excess phenol recovered by short path distillation.
  • the reaction residue is taken up in 50 mL water and 30 mL TBME, the phases are separated and the aqueous phase extracted again with 3x30 mL TBME.
  • the combined organic phases are washed with 50 ml of water and saturated sodium chloride solution, dried over magnesium sulfate and the solvent removed under reduced pressure.
  • the crude product is dissolved in 10 ml of toluene at 50 ° C.
  • the slow addition of n-heptane succeeds in crystallizing the product, which is obtained by filtration and washing with a little cold n-heptane.

Abstract

The invention relates to a process for preparing biaryl alcohols, in which anodic dehydrodimerization of substituted phenols is carried out in the presence of partially fluorinated and/or periluorinated mediators and a supporting electrolyte at a graphite electrode.

Description

VERFAHREN ZUR ANODISCHEN DEHYDRODIMERISIERUNG VON SUBSTITUIERTEN ARYLALKOHOLEN METHOD FOR ANODIC DEHYDRODIMERIZATION OF SUBSTITUTED ARYL ALCOHOLS
Beschreibungdescription
Die Erfindung betrifft ein Verfahren zur Herstellung von Biarylalkoholen, wobei durch anodischen Dehydrodimerisierung von substituierten Phenolen in Gegenwart von teil und/oder perfluorierten Mediatoren und einem Leitsalz an einer Graphitelektrode gearbeitet wird.The invention relates to a process for the preparation of biaryl alcohols, which is carried out by anodic dehydrodimerization of substituted phenols in the presence of partially and / or perfluorinated mediators and a conductive salt on a graphite electrode.
Durch das erfindungsgemäße Verfahren können sehr preiswerte Elektrodenmaterialien, ungeteilte Zellaufbauten sowie lösungsmittelfreie Verfahren angewendet werden. Als Mediatoren können z.B. 1 ,1 ,1 ,3,3,3-Hexafluorisopropanol oder die wesentlich günstigere Trifluoressigsäure eingesetzt werden. Die Aufarbeitung und Gewinnung der gewünschten Biphenole gestaltet sich sehr ein- fach.The method according to the invention makes it possible to use very inexpensive electrode materials, undivided cell structures and solvent-free methods. As mediators, e.g. 1, 1, 1, 3,3,3-hexafluoroisopropanol or the much cheaper trifluoroacetic acid are used. The workup and recovery of the desired biphenols is very simple.
Biaryle sind als solche bekannt und werden industriell hergestellt und eingesetzt. Verbindungen dieser Verbindungsklasse sind u.a. als Rückgrate für Liganden von sehr großem Interesse für stereoselektive Transformationen. Ein möglicher Zugang zu die- ser Substanzklasse ist die elektrochemische oxidative Dimerisierung von Phenolen, die in dem Fachmann bekannten Elektrolyten jedoch unselektiv verläuft. Alternativ zur e- lektrochemischen Dimerisierung von Phenolen werden Eisen(lll)-Salze oder auch andere starke Oxidationsmittel verwendet.Biaryls are known as such and are industrially produced and used. Compounds of this class of compounds are i.a. as backbones for ligands of great interest for stereoselective transformations. One possible approach to this class of substance is the electrochemical oxidative dimerization of phenols, which, however, is nonselective in electrolytes known to those skilled in the art. As an alternative to the electrochemical dimerization of phenols, iron (III) salts or other strong oxidizing agents are used.
G. Lessene und K. S. Feldman beschreiben in Modern Arene Chemistry, Ed: D. Astruc, VCH-Wiley, Weinheim 2002, Seite 479-538, dass sich diese Transformation in einigen Fällen mittel Übergangsmetell-Katalyse auch unter aeroben Bedingungen realisieren lässt. Nachteilige an dieser Synthese ist der Einsatz von Eisenschlorid, da dies zu zahlreichen Nebenprodukten führt. Des Weiteren lässt sich nach diesen aeroben Bedin- gungen nur stark aktivierte Verbindungen umsetzen.G. Lessen and K.S. Feldman describe in Modern Arene Chemistry, Ed. D. Astruc, VCH-Wiley, Weinheim 2002, pages 479-538, that this transformation can be realized in some cases by transition-metal catalysis even under aerobic conditions. The disadvantage of this synthesis is the use of iron chloride, as this leads to numerous by-products. Furthermore, only strongly activated compounds can be reacted according to these aerobic conditions.
Besonders begünstigte und deshalb häufig eingesetzte Substrate weisen annellierte Benzolringe oder sterisch anspruchsvolle Alkylgruppen auf. Als Beispiel kann hier das aus 2-Naphthol hergestellte 2,2'-Dihydroxy-1 ,1 '-binaphthyl (BINOL) gelten.Particularly favored and therefore frequently used substrates have annellated benzene rings or sterically demanding alkyl groups. By way of example, the 2,2'-dihydroxy-1,1'-binaphthyl (BINOL) prepared from 2-naphthol can be used here.
Versucht man 2,4-Dimethylphenol (1 ) analog den Lehrbuchvorschriften von C. E.If 2,4-dimethylphenol (1) is tried in analogy to the textbook instructions of C.E.
Rommel, Staatsexamensarbeit, Münster 2002 und allgemein von H. Lund, M. M. Bai- zer, Organic Electrochemistry: An Introduction and a Guide, 3rd edition, Marcel Dekker, New York 1991 , Chapter 22.lll, 885-908 einer oxidativen Kupplung zu unterwerfen, so erhält man meist als Hauptprodukt nicht das gewünschte ortho,ortho-verknüpfte Pro- dukt 2, sondern ein Derivat des Pummerer Ketons (3). Die Bildung des tricyclischen Gerüstes 3 ist bei para-alkyl-substituierten Phenolen bekannt und findet sich ebenfalls in der Synthese vieler Naturstoffe. 3Rommel, Staatsexamensarbeit, Münster 2002 and in general by H. Lund, MM Baker, Organic Electrochemistry: An Introduction and a Guide, 3rd edition, Marcel Dekker, New York 1991, Chapter 22.lll, 885-908 an oxidative coupling Thus, the main product is usually not the desired ortho, ortho-linked product 2 but a derivative of the Pummerer ketone (3). The formation of the tricyclic skeleton 3 is known for para-alkyl-substituted phenols and is also found in the synthesis of many natural products. 3
Seit einigen Jahren wird die anodische Synthese von Biphenolen, im Speziellen von 3,3',5,5'-Tetramethyl-2,2'-biphenol (2), mit verschiedenen elektrochemischen Methoden intensiv untersucht. In den unterschiedlichsten Elektrolytsystemen zeigte sich bei der direkten Umsetzung ebenfalls eine starke Präferenz zur Bildung des Derivats des Pummerer Ketons (3). Das gewünschte Dehydrodimer 2 wurde lediglich in 3-7 % Ausbeute isoliert. I. M. Malkowsky, C. E. Rommel, K. Wedeking, R. Fröhlich, K. Bergander, M. Nieger, C. Quaiser, U. Griesbach, H. Pütter und S. R. Waldvogel beschrieben inFor several years, the anodic synthesis of biphenols, in particular of 3,3 ', 5,5'-tetramethyl-2,2'-biphenol (2), has been intensively studied by various electrochemical methods. In the most diverse electrolyte systems, direct conversion also showed a strong preference for the formation of the Pummerer ketone derivative (3). The desired dehydrodimer 2 was isolated only in 3-7% yield. I. Malkowsky, C.E. Rommel, K. Wedeking, R. Fröhlich, K. Bergander, M. Nieger, C. Quaiser, U. Griesbach, H. Pütter and S.R. Waldvogel described in
Eur. J. Org. Chem. 2006, 241-245 die Bildung weiterer, zuvor nicht beschriebener pen- tacyclischer Gerüste. Weitergehende Untersuchungen ergaben, dass freie Phenoxyl- radikale für die Bildung des Pummerer Ketons verantwortlich sind. Um eine gezielte Verknüpfung in den ortho-Positionen zu erreichen, wurde, wie von I. M. Malkowsky, R. Fröhlich, U. Griesbach, H. Pütter und S. R. Waldvogel in Eur. J. Inorg. Chem. 2006, 1690-1697 und von I. M. Malkowsky, U. Griesbach, H. Pütter und S. R. Waldvogel in Chem. Eur. J. 2006, 12, 7482-7488 beschrieben, ein Bor-Templat entwickelt. Wie von C. Rommel, I. M. Malkowsky, S. R. Waldvogel, H. Pütter und U. Griesbach in WO-A 2005/075709 beschrieben, gelingt die elektrochemische Umsetzung dieser mehrstufigen Sequenz für eine größere Substratbreite und auch in größeren Maßstäben. Ein zusätzlicher Nachteil neben dem hohen präparativen Aufwand ergab sich aus der Verwendung von Acetonitril im Elektrolyten.Eur. J. Org. Chem. 2006, 241-245 the formation of further unpatterned pentacyclic scaffolds. Further investigations have shown that free phenoxyl radicals are responsible for the formation of the Pummerer ketone. In order to achieve a targeted linkage in the ortho positions, as described by I.M. Malkowsky, R. Fröhlich, U. Griesbach, H. Pütter and S.R. Waldvogel in Eur. J. Inorg. Chem. 2006, 1690-1697 and by I.M. Malkowsky, U. Griesbach, H. Pütter and S.R. Waldvogel in Chem. Eur. J. 2006, 12, 7482-7488, developed a boron template. As described by C. Rommel, I.M. Malkowsky, S.R. Waldvogel, H. Pütter and U. Griesbach in WO-A 2005/075709, the electrochemical conversion of this multistage sequence succeeds for a larger substrate width and also on larger scales. An additional disadvantage in addition to the high preparative effort resulted from the use of acetonitrile in the electrolyte.
Mithilfe von Bor-dotierten Diamantelektroden (BDD) konnte für 2, 4-Dimethylphenol als alleiniges Substrat eine direkte anodische Umsetzung gefunden werden, wie es I. M. Malkowsky, U. Griesbach, H. Pütter und S. R. Waldvogel in Eur. J. Org. Chem. 2006, 4569-4572; und M. Malkowsky, S. R. Waldvogel, H. Pütter und U. Griesbach in WO-A 2006/077204 beschreiben. Das Verhältnis von Biphenol zu Pummerer Keton liegt meist besser als 18:1. Um einen elektrochemischen Abbrand an der BDD-Anode zu vermeiden, wird die Phenolkupplung nur bis zum einem Umsatz von ca. 30% gebracht. Zusätzliche Nachteile dieses Verfahrens bestehen in der geringen Stabilität der BDD-Elektroden, deren Preis sowie der fehlenden Substratbreite.By using boron-doped diamond electrodes (BDD), a direct anodic conversion could be found for 2,4-dimethylphenol as the sole substrate, as described by IM Malkowsky, U. Griesbach, H. Pütter and SR Waldvogel in Eur. J. Org. Chem. 2006, 4569-4572; and M. Malkowsky, S.R. Waldvogel, H. Pütter and U. Griesbach in WO-A 2006/077204. The ratio of biphenol to Pummerer ketone is usually better than 18: 1. In order to avoid electrochemical burnup at the BDD anode, the phenolic coupling is only brought to a conversion of about 30%. Additional disadvantages of this method are the low stability of the BDD electrodes, their price and the lack of substrate width.
Die Aufgabe der vorliegenden Erfindung besteht darin, ein Verfahren bereitzustellen, mit dem die selektive und effiziente oxidative Kupplung von substituierten Phenolen erfolgt ohne in Gegenwart von teuerem Elektrodenmaterial arbeiten zu müssen. Vorzugsweise soll die Kupplung von substituierten Phenolen in ortho-Stellung erfolgen. Diese Aufgabe wird gelöst durch ein Verfahren zur Herstellung von Biarylalkoholen, wobei substituierte Arylalkohole in Gegenwart von teil- und/oder perfluorierten Mediatoren und wenigstens einem Leitsalz mit Hilfe einer Graphitelektrode anodisch dehydro- dimerisiert werden.The object of the present invention is to provide a method with which the selective and efficient oxidative coupling of substituted phenols takes place without having to work in the presence of expensive electrode material. Preferably, the coupling of substituted phenols should take place in the ortho position. This object is achieved by a process for the preparation of biaryl alcohols, wherein substituted aryl alcohols are anodically dehydro-dimerized in the presence of partially and / or perfluorinated mediators and at least one conducting salt with the aid of a graphite electrode.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die OH-Gruppe der eingesetzten, substituierten Arylalkohole direkt am Aromaten sitzt.The process according to the invention is advantageous if the OH group of the substituted aryl alcohols used is seated directly on the aromatic compound.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die eingesetzten substituierten Arylalkohole identisch sind.The process according to the invention is advantageous if the substituted aryl alcohols used are identical.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die eingesetzten substituierten Arylalkohole ein- oder mehrkernig sein können.The process according to the invention is advantageous if the substituted aryl alcohols used can be mononuclear or polynuclear.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die Dimerisierung in ortho- Stellung zur Alkoholgruppe der substituierten Arylalkohole stattfindet.The process according to the invention is advantageous if the dimerization takes place ortho to the alcohol group of the substituted aryl alcohols.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die eingesetzten Mediatoren teil- und/oder perfluorierte Alkohole und/oder Säuren sind.The process according to the invention is advantageous if the mediators used are partially and / or perfluorinated alcohols and / or acids.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn als Mediatoren 1 ,1 ,1 ,3,3,3- Hexafluorisopropanol oder Trifluoressigsäure eingesetzt wird.The process according to the invention is advantageous if the mediators used are 1, 1, 1, 3,3,3-hexafluoroisopropanol or trifluoroacetic acid.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn als Leitsalze solche eingesetzt werden, die ausgewählt sind aus der Gruppe von Alkali, Erdalkali, Tetra(d- bis Cβ- alkyl)ammoniumsalzen.The process according to the invention is advantageous if the conductive salts used are those selected from the group consisting of alkali metal, alkaline earth metal, tetra (C 1 to C 6 alkyl) ammonium salts.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die Gegenionen der Leitsalze ausgewählt sind aus der Gruppe von Sulfat, Hydrogensulfat, Alkylsulfate, Arylsulfate, Halogenide, Phosphate, Carbonate, Alkylphosphate, Alkylcarbonate, Nitrat, Alkoholate, Tetrafluorborat, Hexafluorophosphat und Perchlorat.The process according to the invention is advantageous if the counterions of the conducting salts are selected from the group consisting of sulfate, hydrogensulfate, alkyl sulfates, aryl sulfates, halides, phosphates, carbonates, alkyl phosphates, alkyl carbonates, nitrate, alcoholates, tetrafluoroborate, hexafluorophosphate and perchlorate.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn für die Elektrolyse kein weiteres Lösungsmittel eingesetzt wird.The process according to the invention is advantageous if no further solvent is used for the electrolysis.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn für die Elektrolyse eine Durchflusszelle eingesetzt wird.The process according to the invention is advantageous if a flow cell is used for the electrolysis.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn Stromdichten von 1 bis 1000 mA/cm2 eingesetzt werden. Vorteilhaft ist das erfindungsgemäße Verfahren, wenn die Elektrolyse bei Temperaturen im Bereich von -20 bis 600C und Normaldruck durchgeführt wird.The process according to the invention is advantageous when current densities of 1 to 1000 mA / cm 2 are used. The process according to the invention is advantageous if the electrolysis is carried out at temperatures in the range from -20 to 60 ° C. and normal pressure.
Vorteilhaft ist das erfindungsgemäße Verfahren, wenn als Arylalkohol 2,4-Dimethyl- phenol eingesetzt wird.The process according to the invention is advantageous if 2,4-dimethylphenol is used as the aryl alcohol.
Unter Arylalkohol werden im Rahmen der vorliegenden Erfindung aromatische Alkohole verstanden, bei denen die Hydroxylgruppe direkt an den aromatischen Kern gebunden ist.For the purposes of the present invention, aryl alcohol is understood as meaning aromatic alcohols in which the hydroxyl group is bonded directly to the aromatic nucleus.
Der Aromat, der dem Arylalkohol zugrunde liegt, kann ein- oder mehrkernig sein. Vorzugsweise ist der Aromat einkernig (Phenolderivate) oder zweikernig (Naphtholderiva- te), insbesondere einkernig. Die Arylalkohole können auch noch weitere Substituenten tragen. Diese Substituenten sind unabhängig voneinander ausgewählt aus der Gruppe von Ci-Cio-Alkylgruppen, Halogenen, Ci-Cio-Alkoxygruppen, durch Sauerstoff oder Schwefel unterbrochene Alkylen- oder Arylenreste, Ci-Cio-Alkoxycarboxyl, Nitril, Nitro sowie Ci-Cio-Alkoxycarbamoyl, besonders bevorzugt Methyl, Ethyl, n-Propyl, Isopropyl, n-Butyl, Trifluormethyl, Fluor, Chlor, Brom, lod, Methoxy, Ethoxy, Methylen, Ethylen, Propylen, Isopropylen, Benzyliden, Nitril, Nitro, ganz besonders bevorzugt Methyl, Me- thoxy, Methylen, Ethylen, Trifluormethyl, Fluor und Brom. Mit dem neuen Verfahren kann eine breite Palette an Arylalkoholen eingesetzt werden. Besonders bevorzugt sind elektronenreiche Arene wie Phenol und einfach oder mehrfach substituierte Phenole sowie Naphthol (α- und ß-) und substituierte Derivate davon, ganz besonders bevorzugt sind Phenole und insbesondere ganz besonders bevorzugt sind 4-Alkyl- sowie 2,4-dialkylsubstituierte Phenole.The aromatic, which is based on the aryl alcohol, may be mononuclear or polynuclear. The aromatic is preferably mononuclear (phenol derivatives) or binuclear (naphthol derivatives), in particular mononuclear. The aryl alcohols may also carry further substituents. These substituents are independently selected from the group of C 1 -C 10 -alkyl groups, halogens, C 1 -C 10 -alkoxy groups, alkylene or arylene radicals interrupted by oxygen or sulfur, C 1 -C 10 -alkoxycarboxyl, nitrile, nitro and C 1 -C 10 -alkoxycarbamoyl, particularly preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, trifluoromethyl, fluorine, chlorine, bromine, iodine, methoxy, ethoxy, methylene, ethylene, propylene, isopropylene, benzylidene, nitrile, nitro, very particularly preferably methyl, Me - thoxy, methylene, ethylene, trifluoromethyl, fluorine and bromine. With the new process, a wide range of aryl alcohols can be used. Particularly preferred are electron-rich arenes such as phenol and mono- or polysubstituted phenols and naphthol (α- and ß-) and substituted derivatives thereof, very particularly preferred are phenols, and particularly particularly preferred are 4-alkyl and 2,4-dialkyl-substituted phenols.
Als Substrate für die Elektrodimerisierung nach der vorliegenden Erfindung eignen sich prinzipiell sämtliche Arylalkohole, sofern diese aufgrund ihrer räumlichen Struktur und sterischen Anforderungen zu einer Dimerisierung in der Lage sind. Die Arylalkohole können einkernig, zweikernig, dreikernig oder höherkernig sein. Vorzugsweise sind sie einkernig oder zweikernig, insbesondere einkernig. Weiterhin weisen die Arylalkohole vorzugsweise eine OH-Funktion auf.Suitable substrates for the electrodimerization according to the present invention are in principle all aryl alcohols, provided that they are capable of dimerization due to their spatial structure and steric requirements. The aryl alcohols may be mononuclear, dinuclear, trinuclear or higher nuclear. Preferably, they are mononuclear or dinuclear, in particular mononuclear. Furthermore, the aryl alcohols preferably have an OH function.
Beispiele für geeignete Arylalkohole umfassen Phenol und einfach und mehrfache substituierte Phenole die von der nachfolgenden Formel (I) wiedergegeben werden, in der die Reste R1 bis R4, unabhängig voneinander gleich oder verschieden und aus folgenden Substituenten ausgewählt sind: H, Ci-Cio-Alkyl, Ci-Cio-Alkoxy, Halogen, d- Cio-Alkoxycarboxyl, Nitril sowie Mono- und Di- Ci-Cio-Alkoxycarbamoyl. Examples of suitable aryl alcohols include phenol and mono- and polysubstituted substituted phenols represented by the following formula (I) wherein R1 to R4 are independently the same or different and are selected from the following substituents: H, Ci-Cio-alkyl , C 1 -C 10 -alkoxy, halogen, C 1 -C 10 -alkoxycarboxyl, nitrile and also mono- and di-C 1 -C 10 -alkoxycarbamoyl.
Weitere Beispiele umfassen Naphthol (α- und ß-) und substituierte Derivate davon nach den nachfolgenden Formeln (II) und (III), in denen die Reste R1 bis R7, gleich oder verschieden und aus folgenden Substituenten ausgewählt sind: H, Ci-Cio-Alkyl, Ci-Cio-Alkoxy, Halogen, Ci-Cio-Alkoxycarboxyl, Nitril sowie Mono- und Di- C1-C10- Alkoxycarbamoyl.Further examples include naphthol (α- and β-) and substituted derivatives thereof according to the following formulas (II) and (III), in which the radicals R 1 to R 7, identical or different and selected from the following substituents: H, Ci-Cio Alkyl, Ci-Cio-Alkoxy, halogen, Ci-Cio-Alkoxycarboxyl, nitrile as well as mono- and di-C1-C10-Alkoxycarbamoyl.
Nach Beendigung der Reaktion wird die Elektrolytlösung nach allgemeinen Trennmethoden aufgearbeitet. Hierzu wird die Elektrolytlösung im Allgemeinen zuerst destilliert und die einzelnen Verbindungen in Form von unterschiedlichen Fraktionen getrennt gewonnen. Eine weitere Reinigung kann beispielsweise durch Kristallisation, Destillation, Sublimation oder chromatographisch erfolgen.After completion of the reaction, the electrolyte solution is worked up by general separation methods. For this purpose, the electrolyte solution is generally first distilled and recovered the individual compounds in the form of different fractions separately. Further purification can be carried out, for example, by crystallization, distillation, sublimation or chromatographic.
Die Herstellung des Biarylalkohols erfolgt elektrolytisch, wobei der entsprechende Aryl- alkohol anodisch oxidiert wird. Das erfindungsgemäße Verfahren wird nachfolgend Elektrodimerisierung genannt. Es wurde überraschender weise gefunden, dass durch das erfindungsgemäße Verfahren unter Verwendung von Mediatoren die Biarylalkohole selektiv und in hoher Ausbeute entstehen. Des Weiteren wurde gefunden, dass durch das erfindungsgemäße Verfahren sehr preiswerte Elektrodenmaterialien, ungeteilte Zellaufbauten sowie lösungsmittelfreie Verfahren angewendet werden können. Die Aufarbeitung und Gewinnung der gewünschten Biphenole gestaltet sich sehr einfach. Nach Beendigung der Reaktion wird die Elektrolytlösung nach allgemeinen Trennmethoden aufgearbeitet. Hierzu wird die Elektrolytlösung im Allgemeinen zuerst destilliert und die einzelnen Verbindungen in Form von unterschiedlichen Fraktionen getrennt gewonnen. Eine weitere Reinigung kann beispielsweise durch Kristallisation, Destillation, Sublimation oder chromatographisch erfolgen. Als Mediatoren werden im erfindungsgemäßen Verfahren teil- und/oder perfluorierte Alkohole und/oder Säuren, bevorzugt perfluorierte Alkohole sowie Carbonsäuren, ganz besonders bevorzugt 1 ,1 ,1 ,3,3,3-Hexafluorisopropanol oder Trifluoressigsäure verwendet. Im Elektrolyten sind keine weiteren Lösungsmittel erforderlich.The preparation of the biaryl alcohol is carried out electrolytically, with the corresponding aryl alcohol being oxidized anodically. The process according to the invention is referred to below as electrodimerization. It has surprisingly been found that arise by the process according to the invention using mediators, the biaryl alcohols selectively and in high yield. Furthermore, it has been found that very inexpensive electrode materials, undivided cell structures and solvent-free methods can be used by the method according to the invention. The workup and recovery of the desired biphenols is very simple. After completion of the reaction, the electrolyte solution is worked up by general separation methods. For this purpose, the electrolyte solution is generally first distilled and recovered the individual compounds in the form of different fractions separately. Further purification can be carried out, for example, by crystallization, distillation, sublimation or chromatographic. Partially and / or perfluorinated alcohols and / or acids, preferably perfluorinated alcohols and carboxylic acids, very particularly preferably 1, 1, 1, 3, 3, 3-hexafluoroisopropanol or trifluoroacetic acid are used as mediators in the process according to the invention. No additional solvents are required in the electrolyte.
Die entsprechenden Produkte können durch Kurzwegdestillation und Fällung NMR-rein erhalten werden.The corresponding products can be obtained by short path distillation and precipitation NMR pure.
Die Elektrolyse wird in den üblichen, dem Fachmann bekannten Elektrolysezellen durchgeführt. Geeignete Elektrolysezellen sind dem Fachmann bekannt. Vorzugsweise arbeitet man kontinuierlich in ungeteilten Durchflusszellen oder diskontinuierlich in Becherglaszellen.The electrolysis is carried out in the usual, known in the art electrolysis cells. Suitable electrolysis cells are known to the person skilled in the art. Preferably, one works continuously in undivided flow cells or discontinuously in beaker cells.
Ganz besonders geeignet sind bipolar geschaltete Kapillarspaltzellen oder Plattensta- pelzellen, bei denn die Elektroden als Platten ausgestaltet sind und planparallel ange- ordnet sind wie es in Ullmann's Encyclopedia of Industrial Chemistry, 1999 electronic release, Sixth Edition, VCH-Weinheim, Volumne und in Electrochemistry, Chapter 3.5. special cell designs sowie Chapter 5, Organic Electrochemistry, Subchapter 5.4.3.2 Cell Design beschrieben ist.Particularly suitable are bipolar switched capillary gap cells or Plattenstapelzellen, in which the electrodes are designed as plates and are arranged plane-parallel as in Ullmann's Encyclopedia of Industrial Chemistry, 1999 electronic release, Sixth Edition, VCH-Weinheim, Volumne and in Electrochemistry , Chapter 3.5. special cell designs as well as Chapter 5, Organic Electrochemistry, Subchapter 5.4.3.2 Cell Design.
Die Stromdichten, bei denen das Verfahren durchgeführt wird, betragen im allgemeinen 1 - 1000, bevorzugt 5 - 100 mA/cm2. Die Temperaturen betragen üblicherweise -20 bis 600C, bevorzugt 10 bis 600C. Im Allgemeinen wird bei Normaldruck gearbeitet. Höhere Drücke werden bevorzugt dann angewandt, wenn bei höheren Temperaturen gearbeitet werden soll, um ein Sieden der Ausgangsverbindungen bzw. Cosolventien bzw. Mediatoren zu vermeiden.The current densities at which the process is carried out are generally 1 to 1000, preferably 5 to 100 mA / cm 2 . The temperatures are usually from -20 to 60 ° C., preferably from 10 to 60 ° C. The reaction is generally carried out under atmospheric pressure. Higher pressures are preferably used when operating at higher temperatures to avoid boiling of the co-solvents or mediators.
Als Anodenmaterialien eignen sich beispielsweise Edelmetalle wie Platin oder Metalloxide wie Ruthenium oder Chromoxid oder Mischoxide des Typs RuOxTiOx sowie Diamantelektroden. Bevorzugt sind Graphit oder Kohleelektroden. Als Kathodenmaterial kommen beispielsweise Eisen, Stahl, Edelstahl, Nickel oder E- delmetalle wie Platin sowie Graphit oder Kohlematerialien sowie Diamantelektroden in Betracht. Bevorzugt ist das System Graphit als Anode und Kathode, Graphit als Anode und Nickel, Edelstahl oder Stahl als Kathode sowie Platin als Anode und Kathode.Suitable anode materials are, for example, noble metals such as platinum or metal oxides such as ruthenium or chromium oxide or mixed oxides of the type RuO x TiO x and diamond electrodes. Preference is given to graphite or carbon electrodes. As the cathode material, for example, iron, steel, stainless steel, nickel or E- delmetalle such as platinum and graphite or carbon materials and diamond electrodes into consideration. The system is preferably graphite as the anode and cathode, graphite as the anode and nickel, stainless steel or steel as the cathode and platinum as the anode and cathode.
Zur Durchführung der Elektrolyse wird die Arylalkoholverbindung in einem geeigneten Lösungsmittel gelöst. Es eignen sich die üblichen, dem Fachmann bekannten Lösungsmittel, vorzugsweise Lösungsmittel aus der Gruppe der polaren protischen und polaren aprotischen Lösungsmittel. Besonders bevorzugt dient die Arylalkoholverbindung selbst als Lösungsmittel und Reagenz.To carry out the electrolysis, the aryl alcohol compound is dissolved in a suitable solvent. The usual solvents known to the person skilled in the art, preferably solvents from the group of polar protic and polar aprotic solvents, are suitable. Particularly preferably, the aryl alcohol compound itself serves as a solvent and reagent.
Beispiele für polare aprotische Lösungsmittel umfassen Nitrile, Amide, Carbonate, E- ther, Harnstoffe, Chlorkohlenwasserstoffe.Examples of polar aprotic solvents include nitriles, amides, carbonates, ethers, ureas, chlorinated hydrocarbons.
Beispiele für besonders bevorzugte polare aprotische Lösungsmittel umfassen Actonitril, Dimethylformamid, Dimethylsulfoxid, Propylencarbonat und Dichlormethan. Beispiele für polare protische Lösungsmittel umfassen Alkohole, Carbonsäuren und Amide.Examples of particularly preferred polar aprotic solvents include Actonitrile, dimethylformamide, dimethyl sulfoxide, propylene carbonate and dichloromethane. Examples of polar protic solvents include alcohols, carboxylic acids and amides.
Beispiele für besonders bevorzugte polare protische Lösungsmittel umfassen Metha- nol, Ethanol, Propanol, Butanol, Pentanol und Hexanol. Diese können auch teilweise oder vollständig halogeniert sein, wie z.B. 1 ,1 ,1 ,3,3,3-Hexafluorisopropanol (HFIP) o- der Trifluoressigsäure (TFA).Examples of particularly preferred polar protic solvents include methanol, ethanol, propanol, butanol, pentanol and hexanol. These may also be partially or completely halogenated, e.g. 1, 1, 1, 3,3,3-hexafluoroisopropanol (HFIP) or trifluoroacetic acid (TFA).
Gegebenenfalls setzt man der Elektrolyselösung übliche Cosolvenzien zu. Dabei handelt es sich um die in der organischen Chemie üblichen inerten Lösungsmittel mit ei- nem hohen Oxidationspotential. Beispielhaft genannt seinen Dimethylcarbonat, Propylencarbonat, Tetrahydrofuran, Dimethoxyethan, Acetonitril oder Dimethylformamid. Als Leitsalze, die in der Elektrolyselösung enthalten sind, handelt es sich im Allgemeinen um Alkali, Erdalkali, Tetra(d- bis C6-alkyl)ammonium-, bevorzugt Tri(Ci- bis Ce- alkyl)-methylammoniumsalze. Als Gegenion kommen Sulfat, Hydrogensulfat, Alkylsul- fate, Arylsulfate, Halogenide, Phosphate, Carbonate, Alkylphosphate, Alkylcarbonate, Nitrat, Alkoholate, Tetrafluorborat, Hexafluorophosphat oder Perchlorat in Betracht. Weiterhin kommen die von den vorstehend genannten Anionen abgeleiteten Säuren als Leitsalze in Betracht. Bevorzugt sind Methyltributylammoniummethylsulfate (MTBS), Methyltriethylammoni- ummethylsulfat (MTES), Methyltripropylmethylammoniummethylsulfate, oder Tetrabu- tylammonium, Tetrafluoroborat (TBABF).Optionally, the electrolysis solution is added to customary cosolvents. These are the inert solvents customary in organic chemistry and have a high oxidation potential. Examples include its dimethyl carbonate, propylene carbonate, tetrahydrofuran, dimethoxyethane, acetonitrile or dimethylformamide. Conducting salts which are contained in the electrolysis solution are generally alkali metal, alkaline earth metal, tetra (C 1 -C 6 -alkyl) ammonium, preferably tri (cis-bisalkyl) -methylammonium salts. Suitable counterions are sulfate, bisulfate, alkyl sulfates, aryl sulfates, halides, phosphates, carbonates, alkyl phosphates, alkyl carbonates, nitrate, alcoholates, tetrafluoroborate, hexafluorophosphate or perchlorate. Furthermore, the acids derived from the abovementioned anions are suitable as conductive salts. Preference is given to methyltributylammonium methylsulfates (MTBS), methyltriethylammonium methylsulfate (MTES), methyltripropylmethylammonium methylsulfates, or tetrabutylammonium, tetrafluoroborate (TBABF).
Beispiele: (Tabellen mit Umsetzungen)Examples: (tables with conversions)
Tabelle 1 :Table 1 :
Umsetzung von 2,4-Dimethylphenol an Graphit unter Verwendung von HFIP^Reaction of 2,4-dimethylphenol on graphite using HFIP ^
HFIP: 1 ,1 ,1 ,3,3,3-HexafluorisopropanolHFIP: 1, 1, 1, 3,3,3-hexafluoroisopropanol
Tabelle 2:Table 2:
Umsetzung von 2,4-Dimethylphenol an Graphit unter Verwendung von CarbonsäurenReaction of 2,4-dimethylphenol on graphite using carboxylic acids
TFA: Trifluoressigsäure; AcOH: Essigsäure; Phenol: 2,4-Dimethylphenol; MTES: MethyltriethylammoniummethylsulfatTFA: trifluoroacetic acid; AcOH: acetic acid; Phenol: 2,4-dimethylphenol; MTES: methyltriethylammonium methyl sulfate
Tabelle 3: Umsetzung von 2-Brom-4-methylphenol an GraphitTable 3: Reaction of 2-bromo-4-methylphenol on graphite
Phenol: 2-Brom-4-methylphenol; a: N,N-Dimethylpyrrolidiniummethylsulfat; b: Ausbeute unter Berücksichtigung des rückgewonnenen Phenols; c: Isolierung durch Kristallisation aus Toluol und chromatographisch; d: Isolierung durch Kristallisation aus 'PrOH:Wasser und chromatographisch.Phenol: 2-bromo-4-methylphenol; a: N, N-dimethylpyrrolidinium methylsulfate; b: yield considering the recovered phenol; c: isolation by crystallization from toluene and chromatographic; d: isolation by crystallization from 'PrOH: water and chromatographic.
Beispiel 1 : Anodische Oxidation von 2,4-Dimethylphenol an Graphitelektroden mit Trifluoressig- säureExample 1 : Anodic oxidation of 2,4-dimethylphenol on graphite electrodes with trifluoroacetic acid
In einer ungeteilten Standardelektrolysezelle mit Graphitanode und -kathode (A = 9 cm2) wird der Elektrolyt bestehend aus 15.90 g (0,1301 mol, 53 Gew.-%) 2,4- Dimethylphenol, 1.00 g (4.4 mmol, 3 Gew.-%) Methyltriethylammoniummethylsulfat und 9 ml_ (44 Gew.-%) Trifluoressigsäure vorgelegt. Unter galvanostatischen Bedingungen wird bei 300C und einer Stromdichte von 10 mA/cm2 eine Elektrolyse durchgeführt. Dabei werden 9669 C (0.77 F/mol) bei einer maximalen Klemmspannung von 18 V aufgebracht. Nach Beenden der Reaktion wird der Elektrolyt mit Toluol in einen Kolben überführt und nachfolgend Trifluoressigsäure sowie Toluol bei Raumdruck destillativ entfernt. Anschließend werden 5.89 g überschüssiges Phenol mittels Kurzwegdestilla- tion bei 4.5x10"3 mbar zurückgewonnen. Der Reaktionsrückstand wird in 30 ml_ wäss- rigem Isopropanol ('PrOHihbO = 4:1) aufgenommen. Durch Lagerung über Nacht bei 4°C gelingt die Kristallisation des Produkts, welches mittels Filtration und Waschen mit wenig kaltem n-Heptan erhalten wird (4.24 g). Weiteres Produkt kann aus dem Filtrat durch kurze säulenchromatographische Aufreinigung an Kieselgel (CH:EE=98:2) iso- liert werden (2.15 g). Insgesamt werden 6.39 g (0,026 mol, 64%), wobei überschüssiges Phenol bei der Ausbeute berücksichtigt wird, leicht rötliches, kristallines Produkt erhalten.In an undivided standard electrolysis cell with graphite anode and cathode (A = 9 cm 2 ), the electrolyte consisting of 15.90 g (0.1301 mol, 53 wt .-%) of 2,4-dimethylphenol, 1.00 g (4.4 mmol, 3 wt. -%) Methyltriethylammoniummethylsulfat and 9 ml_ (44 wt .-%) submitted trifluoroacetic acid. Under galvanostatic conditions, an electrolysis is carried out at 30 0 C and a current density of 10 mA / cm 2 . 9669 C (0.77 F / mol) are applied at a maximum clamping voltage of 18 V. After completion of the reaction, the electrolyte is transferred with toluene in a flask and subsequently removed by distillation trifluoroacetic acid and toluene at room pressure. Subsequently, 5.89 g of excess phenol are recovered by short path distillation at 4.5 × 10 -3 mbar and the reaction residue is taken up in 30 ml of aqueous isopropanol ('PrOHihbO = 4: 1) Product, which is obtained by filtration and washing with a little cold n-heptane (4.24 g). Further product can be isolated from the filtrate by short column chromatographic purification on silica gel (CH: EE = 98: 2) (2.15 g). Overall, 6.39 g (0.026 mol, 64%), taking into account excess phenol in the yield, gives a slightly reddish, crystalline product.
Schmelzpunkt: 133°C; RF-Wert (CH:EE=95:5): 0.33; 1H-NMR (400 MHz, CDCI3): δ = 2.29 (s, 12H, CH3), 4.84 (s, 2H, OH), 6.88 (s, 2H, 4-H), 7.01 (s, 2H, 6-H); 13C-NMR (100 MHz, CDCI3): δ = 16.15 (3-CH3), 20.41 (5-CH3), 122.23 (C-1 ), 125.17 (C-3),Melting point: 133 ° C; R F value (CH: EE = 95: 5): 0.33; 1 H-NMR (400 MHz, CDCl 3 ): δ = 2.29 (s, 12H, CH 3 ), 4.84 (s, 2H, OH), 6.88 (s, 2H, 4-H), 7.01 (s, 2H, 6-H); 13 C-NMR (100 MHz, CDCl 3 ): δ = 16.15 (3-CH 3 ), 20.41 (5-CH 3 ), 122.23 (C-1), 125.17 (C-3),
128.51 (C-6), 129.98 (C-5), 131.97 (C-4), 149.13 (C-2); HRMS: m/z für [Ci6Hi902]+ berechnet 243.1380, gefunden 243.1389; MS (ESI+): m/z (%): 243.1 (100) [Ci6Hi902]+.128.51 (C-6), 129.98 (C-5), 131.97 (C-4), 149.13 (C-2); HRMS: m / z for [Ci 6 Hi 9 O 2 ] + calculated 243.1380, found 243.1389; MS (ESI +): m / z (%): 243.1 (100) [Ci 6 Hi 9 0 2 ] + .
Beispiel 2: Anodische Oxidation von 2-Brom-4-methylphenol an Graphit-elektrodenExample 2: Anodic oxidation of 2-bromo-4-methylphenol on graphite electrodes
In einer ungeteilten Standardelektrolysezelle mit Graphitanode und -kathode (A = 9 cm2) wird der Elektrolyt bestehend aus 20.02 g (0,107 mol, 53 Gew.-%) 2-Brom-4- methylphenol, 1.00 g (4.4 mmol, 3 Gew.-%) Methyltriethylammoniummethylsulfat und 11 ml_ (44 Gew.-%) Trifluoressigsäure vorgelegt. Unter galvanostatischen Bedingungen wird bei 30 0C und einer Stromdichte von 10 mA/cm2 eine Elektrolyse durchge- führt. Dabei werden 7950 C (0.77 F/mol) bei einer maximalen Klemmspannung von 22 V aufgebracht. Nach Beenden der Reaktion wird der Elektrolyt mit Toluol in einen Kolben überführt und nachfolgend Trifluoressigsäure sowie Toluol bei Raumdruck destillativ entfernt. Anschließend werden 9.08 g überschüssiges Phenol mittels Kurz- wegdestillation bei 5.0x10"3 mbar zurückgewonnen. Der Reaktionsrückstand wird in 30 ml_ wässrigem Isopropanol ('PrOHihbO = 4:1 ) aufgenommen. Durch Lagerung über Nacht bei 4 0C gelingt die Kristallisation des Produkts. Dieses wird in wenig MTBE aufgenommen und über Cellite filtriert. Durch entfernen des Lösungsmittels wird reines Produkt erhalten (1.35 g). Weiteres Produkt kann aus dem Filtrat durch säulenchroma- tographische Aufreinigung an Kieselgel (CH:EE=95:5) isoliert werden (6.90 g). Insgesamt werden 8.25 g (0,022 mol, 76%), wobei überschüssiges Phenol bei der Ausbeute berücksichtigt wird, farbloses, kristallines Produkt erhalten.In an undivided standard electrolysis cell with graphite anode and cathode (A = 9 cm 2 ), the electrolyte consisting of 20.02 g (0.107 mol, 53 wt .-%) of 2-bromo-4-methylphenol, 1.00 g (4.4 mmol, 3 wt. -%) Methyltriethylammoniummethylsulfat and 11 ml_ (44 wt .-%) submitted trifluoroacetic acid. Under galvanostatic conditions at 30 0 C and a current density of 10 mA / cm 2, an electrolysis carried leads. 7950 C (0.77 F / mol) are applied at a maximum clamping voltage of 22 V. After completion of the reaction, the electrolyte is transferred with toluene in a flask and subsequently removed by distillation trifluoroacetic acid and toluene at room pressure. Subsequently, 9:08 g of excess phenol by short wegdestillation recovered at 5.0x10 "3 mbar The reaction residue is dissolved in 30 ml of aqueous isopropanol ( 'PrOHihbO = 4: 1).. Was added, the crystallization of the product is achieved by overnight storage at 4 0 C. This is taken up in a small amount of MTBE and filtered through Celite, removing the solvent gives pure product (1.35 g), and further product can be isolated from the filtrate by column chromatography on silica gel (CH: EE = 95: 5) (6.90 g) A total of 8.25 g (0.022 mol, 76%), taking into account excess phenol in the yield, gave colorless, crystalline product.
Schmelzpunkt: 144-145 0C; RF-Wert (CH:EE=95:5): 0.06; 1H-NMR (300 MHz, CDCI3): δ = 2.31 (s, 6H, CH3), 5.80 (s, 2H, OH), 6.88 (d, 4JH,H = 2.1 Hz, 2H, 6-H), 7.01 (d, 4JH,H = 2.1 Hz, 2H, 4-H); 13C-NMR (75 MHz, CDCI3): δ = 20.24 (5-CH3), 110.94 (C-3), 125.33 (C-1 ), 131.44 (C-5), 131.60 (C-6), 132.58 (C-4), 147.11 (C-2).Melting point: 144-145 0 C; R F value (CH: EE = 95: 5): 0.06; 1 H-NMR (300 MHz, CDCl 3 ): δ = 2.31 (s, 6H, CH 3 ), 5.80 (s, 2H, OH), 6.88 (d, 4 JH, H = 2.1 Hz, 2H, 6-H ), 7.01 (d, 4 JH, H = 2.1 Hz, 2H, 4-H); 13 C-NMR (75 MHz, CDCl 3 ): δ = 20.24 (5-CH 3 ), 110.94 (C-3), 125.33 (C-1), 131.44 (C-5), 131.60 (C-6), 132.58 (C-4), 147.11 (C-2).
Beispiel 3:Example 3:
Anodische Oxidation von 2,4-Dimethylphenol an Graphitelektroden mit HFIPAnodic oxidation of 2,4-dimethylphenol on graphite electrodes with HFIP
In einer ungeteilten Standardelektrolysezelle mit Graphitanode und -kathode (A = 9 cm2) wird der Elektrolyt bestehend aus 15.98 g (0,1308 mol, 52 Gew.-%) 2,4-Di- methylphenol, 1.00 g (4.4 mmol, 1 Gew.-%) Methyltriethylammoniummethylsulfat und 9 mL (47 Gew.-%) Hexafluorisopropanol vorgelegt. Unter galvanostatischen Bedingungen wird bei 30 0C und einer Stromdichte von 10 mA/cm2 eine Elektrolyse durchgeführt. Dabei werden 9721 C (0.77 F/mol) bei einer maximalen Klemmspannung von 12.8 V aufgebracht. Nach Beenden der Reaktion wird zunächst das Lösungsmittel ent- fernt und anschließend überschüssiges Phenol mittels Kurzwegdestillation zurückgewonnen. Der Reaktionsrückstand wird in 50 mL Wasser und 30 mL TBME aufgenommen, die Phasen getrennt und die wässrige Phase nochmals mit 3x30 mL TBME extrahiert. Die vereinigten organischen Phasen werden mit jeweils 50 mL Wasser und gesättigter Natriumchlorid-Lösung gewaschen, über Magnesiumsulfat getrocknet und das Lösungsmittel unter vermindertem Druck entfernt. Das Rohprodukt wird in 10 mL Toluol bei 500C gelöst. Durch langsame Zugabe von n-Heptan gelingt die Kristallisation des Produkts, welches mittels Filtration und Waschen mit wenig kaltem n-Heptan erhalten wird. Weiteres Produkt kann aus dem Filtrat durch säulenchromatographische Aufreinigung an Kieselgel (CH:EE=98:2, dann 95:5) isoliert werden. Insgesamt werden 4,43 g (0,018 mol, 28%) farbloses, kristallines Produkt erhalten. Schmelzpunkt: 135-136 0C; RF-Wert (CH:EE=95:5): 0.33; 1H-NMR (300 MHz, CDCI3): δ = 2.29 (s, 12H, CH3), 5.01 (s, 2H, OH), 6.88 (s, 2H, 4-H), 7.01 (s, 2H, 6-H); 13C-NMR (75 MHz, CDCI3): δ = 16.14 (3-CH3), 20.41 (5-CH3), 122.17 (C-1), 125.16 (C-3), 128.49 (C-6), 130.00 (C-5), 132.00 (C-4), 149.13 (C-2). In an undivided standard electrolysis cell with graphite anode and cathode (A = 9 cm 2 ), the electrolyte consisting of 15.98 g (0.1308 mol, 52 wt .-%) of 2,4-dimethylphenol, 1.00 g (4.4 mmol, 1 Wt .-%) Methyltriethylammoniummethylsulfat and 9 mL (47 wt .-%) hexafluoroisopropanol presented. Under galvanostatic conditions, an electrolysis is carried out at 30 0 C and a current density of 10 mA / cm 2 . 9721 C (0.77 F / mol) are applied at a maximum clamping voltage of 12.8 V. After completion of the reaction, the solvent is first removed and then excess phenol recovered by short path distillation. The reaction residue is taken up in 50 mL water and 30 mL TBME, the phases are separated and the aqueous phase extracted again with 3x30 mL TBME. The combined organic phases are washed with 50 ml of water and saturated sodium chloride solution, dried over magnesium sulfate and the solvent removed under reduced pressure. The crude product is dissolved in 10 ml of toluene at 50 ° C. The slow addition of n-heptane succeeds in crystallizing the product, which is obtained by filtration and washing with a little cold n-heptane. Further product can be isolated from the filtrate by column chromatography on silica gel (CH: EE = 98: 2, then 95: 5). A total of 4.43 g (0.018 mol, 28%) of colorless, crystalline product are obtained. Melting point: 135-136 0 C; R F value (CH: EE = 95: 5): 0.33; 1 H-NMR (300 MHz, CDCl 3 ): δ = 2.29 (s, 12H, CH 3 ), 5.01 (s, 2H, OH), 6.88 (s, 2H, 4-H), 7.01 (s, 2H, 6-H); 13 C-NMR (75 MHz, CDCl 3 ): δ = 16.14 (3-CH 3 ), 20.41 (5-CH 3 ), 122.17 (C-1), 125.16 (C-3), 128.49 (C-6) , 130.00 (C-5), 132.00 (C-4), 149.13 (C-2).

Claims

Patentansprüche claims
1. Verfahren zur Herstellung von Biarylalkoholen, wobei substituierte Arylalkohole in Gegenwart von teil- und/oder perfluorierten Mediatoren und wenigstens einem Leitsalz mit Hilfe einer Graphitelektrode anodisch dehydrodimerisiert werden.1. A process for the preparation of biaryl alcohols, wherein substituted aryl alcohols are anodically dehydrodimerisiert in the presence of partially and / or perfluorinated mediators and at least one conducting salt by means of a graphite electrode.
2. Verfahren nach Anspruch 1 , wobei die OH-Gruppe der eingesetzten Arylalkohole direkt an den Aromaten gebunden ist.2. The method of claim 1, wherein the OH group of the aryl alcohols used is bonded directly to the aromatic.
3. Verfahren nach einem der Ansprüche 1 bis 2, wobei die eingesetzten substituierten Arylalkohole identisch sind.3. The method according to any one of claims 1 to 2, wherein the substituted aryl alcohols used are identical.
4. Verfahren nach einem der Ansprüche 1 bis 3, wobei die eingesetzten substituierten Arylalkohole ein- oder mehrkernig sein können.4. The method according to any one of claims 1 to 3, wherein the substituted aryl alcohols used may be mononuclear or polynuclear.
5. Verfahren nach einem der Ansprüche 1 bis 4, wobei die Dimerisierung in ortho- Stellung zur Alkoholgruppe der Arylalkohole stattfindet.5. The method according to any one of claims 1 to 4, wherein the dimerization takes place ortho to the alcohol group of the aryl alcohols.
6. Verfahren nach einem der Ansprüche 1 bis 5, wobei die eingesetzten Mediatoren teil- und/oder perfluorierte Alkohole und/oder Säuren sind.6. The method according to any one of claims 1 to 5, wherein the mediators used are partially and / or perfluorinated alcohols and / or acids.
7. Verfahren nach einem der Ansprüche 1 bis 6, wobei als Mediatoren 1 ,1 ,1 ,3,3,3- Hexafluorisopropanol oder Trifluoressigsäure eingesetzt wird.7. The method according to any one of claims 1 to 6, wherein as mediators 1, 1, 1, 3,3,3-hexafluoroisopropanol or trifluoroacetic acid is used.
8. Verfahren nach einem der Ansprüche 1 bis 7, wobei als Leitsalze solche eingesetzt werden, die ausgewählt sind aus der Gruppe von Alkali, Erdalkali, Tetra(d- bis C6-alkyl)ammoniumsalzen.8. The method according to any one of claims 1 to 7, wherein as the conductive salts used are those which are selected from the group of alkali, alkaline earth, tetra (C 1 to C 6 alkyl) ammonium salts.
9. Verfahren nach einem der Ansprüche 1 bis 8, wobei die Gegenionen der Leitsal- ze ausgewählt sind aus der Gruppe von Sulfat, Hydrogensulfat, Alkylsulfate, A- rylsulfate, Halogenide, Phosphate, Carbonate, Alkylphosphate, Alkylcarbonate, Nitrat, Alkoholate, Tetrafluorborat, Hexafluorophosphat und Perchlorat.9. The process as claimed in any of claims 1 to 8, where the counterions of the conductive salts are selected from the group consisting of sulfate, hydrogensulfate, alkyl sulfates, aryl sulfates, halides, phosphates, carbonates, alkyl phosphates, alkyl carbonates, nitrate, alcoholates, tetrafluoroborate, Hexafluorophosphate and perchlorate.
10. Verfahren nach einem der Ansprüche 1 bis 9, wobei für die Elektrolyse kein wei- teres Lösungsmittel eingesetzt wird.10. The method according to any one of claims 1 to 9, wherein no further teres solvent is used for the electrolysis.
1 1. Verfahren nach einem der Ansprüche 1 bis 10, wobei für die Elektrolyse eine Durchflusszelle eingesetzt wird.1 1. The method according to any one of claims 1 to 10, wherein a flow cell is used for the electrolysis.
12. Verfahren nach einem der Ansprüche 1 bis 1 1 , wobei Stromdichten von 1 bis 1000 mA /cm2 eingesetzt werden. 12. The method according to any one of claims 1 to 1 1, wherein current densities of 1 to 1000 mA / cm 2 are used.
13. Verfahren nach einem der Ansprüche 1 bis 12, wobei die Elektrolyse bei Temperaturen im Bereich von -20 bis 600C und Normaldruck durchgeführt wird.13. The method according to any one of claims 1 to 12, wherein the electrolysis is carried out at temperatures in the range of -20 to 60 0 C and atmospheric pressure.
14. Verfahren nach einem der Ansprüche 1 bis 13, wobei als Arylalkohol 2,4-Di- methylphenol eingesetzt wird. 14. The method according to any one of claims 1 to 13, wherein is used as the aryl alcohol 2,4-dimethylmethylphenol.
EP09782303A 2008-09-01 2009-08-28 Method for anodic dehydrodimerisation of substituted phenols Not-in-force EP2318569B1 (en)

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