WO2008145627A1 - Electrochemical oxidation at allyl groups - Google Patents

Abstract

Process for the electrochemical oxidation of an organic compound at a carbon atom which is bound directly to a nonaromatic double bond (alpha position relative to the double bond), characterized in that a mediator is used.

Description

 Electrochemical oxidation on allyl groups

description

The invention relates to a process for the electrochemical oxidation of an organic compound on a carbon atom, which is bonded directly to a non-aromatic double bond (alpha position to the double bond), characterized in that a mediator is used.

Many chemical syntheses require oxidation of allyl-containing C atoms, i. in alpha position to a non-aromatic double bond. For example, mention may be made of e.g. the oxidation of β-ionone to 4-oxo-β-ionone or β-carotene to canthaxantin.

DE-A 27 04 406 describes the oxidation of such compounds with halogenated oxygen acids or their salts as oxidizing agents. Elisabeth Becher et al., Helvetia Chimica Acta. Vol. 64 (7), pages 2419 to 2434 (1981) use pyridinium chlorochromate as the oxidizing agent in the preparation. For syntheses on an industrial scale, in contrast, simple processes are desired which, if possible, do without halogen-containing oxidants or chromates, have a high yield and selectivity, and require no complicated work-up of the reaction products.

Electrochemical oxidations, including those using mediators, are known in principle. Mediators are understood as meaning redox pairs which allow indirect electrochemical oxidation. The mediator is electrochemically transferred to the higher oxidation state, then acts as an oxidant and then regenerates again by electrochemical oxidation. Thus, Pierre Vaudano et al, Chimia 49, pages 12-16 (1995) describes the electrochemical oxidation of aromatics, e.g. of p-tert-butyl-benzaldehyde from p-tert-butyl-toluene with manganese sulfates as mediators. DE-A 100 45 664 relates to the use of mediators in electrochemical processes using a diamond electrode, Ce (III / IV), Mn (II / III), Mn (II / IV) and V (III / IV) being among others and V (IVA /).

The object of the invention was a process for the oxidation of a C atom, which is bonded directly to a non-aromatic double bond (alpha position to the double bond), which works as possible without halogen-containing oxidant and without chromates. With high yield and selectivity, the process should be as simple and effective.

Accordingly, the method defined above was found. In the process of the present invention, an organic compound is oxidized on a carbon atom directly bonded to a non-aromatic double bond. The C atom is also referred to as an alpha-C atom or allylic C atom. This C atom preferably has at least one hydrogen atom as a substituent. In addition to the at least one hydrogen atom, the C atom may, for example, still have a hydroxyl group as a substituent; two hydrogen atoms are particularly preferred as substituents on the alpha-C atom to be oxidized.

Preferably, the non-aromatic double bond is part of a non-aromatic ring system, more preferably a cyclohexene ring system. In particular, the organic compound is cyclohexene and its derivatives.

In the cyclohexene ring, there are two C atoms adjacent to the double bond. Preferably, one of these C atoms is protected by appropriate substitution so that oxidation occurs selectively only on the other remaining C atom. The protected C atom preferably has no more hydrogens than substituents. In particular, it has only alkyl groups, e.g. C1-C4 alkyl groups as substituents.

Particularly preferred organic compounds are those of the formula I.

in which

X represents a hydrogen atom or a hydroxyl group

R 1, R 2 and R 3 independently of one another represent a C 1 to C 4 alkyl group and

Y is an organic radical having at least 2 C atoms.

Preferably, X is an H atom and R 1, R 2 and R 3 are a methyl group.

Y is preferably an organic radical having at least 2 C atoms, in particular an organic radical having 2 to 40 C atoms; the organic radical may optionally contain oxygen atoms in the form of carbonyl groups. Y is particularly preferably an aliphatic organic radical having 2 to 40 carbon atoms which contains a carbonyl group.

In particular, the aliphatic radical contains at least one further double bond. In a preferred embodiment, the double bond of the cyclohexene ring is in conjugation with at least one further non-aromatic double bond of the radical Y. two double bonds are in conjugation when they are connected via a single C-C single bond.

Preferred organic compounds are e.g.

ß-Jonon of the formula

ß-Jonon

ß-ionone

ß-carotene of the formula

ß-Carotin

beta-carotene

Mention may also be made of the following compounds (double bond isomers (E ₁ Z) are included instead of OH also aldehydes (= 0) and aldehyde acetals (OR) 2 conceivable):

ß-vinyljonol (E ₁ Z), and derivatives ß-Jonylidenethanol (E, Z) and derivatives X = OH, OAc, Cl, Br X = OH, OR, = 0, (OR) ₂ , OC (= O) - R, Cl, Br, SO ₂ Ph

R = C1 to C8 alkyl

Retinol (E ₁ Z) and derivatives

X = OH, OR, = O, (OR) ₂ , OC (= O) -R, Cl, Br, SO ₂ Ph

R = C1 to C8 alkyl

In the above formulas, the dashed line to X indicates a double bond when X is a carbonyl group (= 0) in the above list).

The C atom to be oxidized is preferably oxidized to a carbonyl group.

β-ionone becomes 4-oxo-β-ionone of the formula

ß-Jonon

ß-ionone

4-oxo-ß-ionone

and β-carotene to canthaxantine of the formula

ß-Carotin

beta-carotene

oxidiert.

oxidized.

In the electrochemical oxidation according to the invention, a mediator is used.

Mediators are understood as meaning redox pairs which allow indirect electrochemical oxidation. The mediator is converted electrochemically into the higher oxidation state, then acts as an oxidant and then regenerates again by electrochemical oxidation. It is therefore an indirect electrochemical oxidation of the organic compound, since the mediator is the oxidizing agent. The oxidation of the organic compound with the mediator in the oxidized form can thereby be carried out in the electrochemical cell in which the mediator has been converted into the oxidized form, or in one or more separate reactors ("ex-cell process") The latter method has the advantage that any remaining traces of the organic compound to be oxidized do not interfere with the production or regeneration of the mediator.

Suitable mediators are compounds which can be present in two oxidation states, act as oxidants in the higher oxidation state and can be regenerated electrochemically.

For example, salts or complexes of the following redox couples can be used as mediators: Ce (III / IV), Cr (II / III), Cr (III / VI), Ti (II / III), V (II / III), V ( III / IV), V (IVA /), Ag (1 / ll), AgOVAgO ", Cu (1 / ll), Sn (II / IV), Co (II / III), Mn (II / III, Mn ( II / IV), Os (IVA / III), Os (III / IV), Br ₂ / Br7Br0 _3, I- / I2, I3VI2 IO3VIO4 ^"Fremys salt (dipotassium nitrosodisulfonate) or also organic mediators like ABTS (2,2 '-Azino-bis- (3-ethylbenzothiazoline-6-sulfonic acid), TEMPO, Vio- logene such as violuric acid, NADVNADH, NADPVNADPH, where the systems mentioned may also be metal complexes with various ligands or solvent ligands , such as H ₂ O, NH ₃ , CN, OH, SCN, halogens, O ₂ , acetylacetonate, dipyridyl, phenanthroline or 1, 10-phenanthroline 5,6-dione.

Preferred mediators are compounds, in particular salts, of cerium, vanadium and manganese. Very particular preference is given to compounds, in particular salts of manganese.

In a particular embodiment, the redox couple Mn (II / IV) is used as a mediator.

The mediator is preferably in the form of a salt and is sufficiently soluble in the solvent used in the electrochemical oxidation. If the oxidized form of Mediators as in the case of the system Mn (ll / IV) is present as a water-insoluble oxide (M1-1O2), it is used as a suspension.

Suitable anions of the salts are the salts of strong mineral or oxo acids, e.g. Sulfates, phosphates or sulfonates.

In the case of the manganese compound as a mediator in particular the sulfate is used. The following reactions take place here:

1.) Electrochemical Generation of Mn (III) Sulfate:

2 MnSO ₄ + H ₂ SO ₄ -> Mn ₂ (SO ₄ ) S + H ₂

2.) Disproportionation of the Mn (III) Sulfate:

Mn ₂ (SO ₄ ) S + 2 H ₂ O -> MnO ₂ + MnSO ₄ + 2 H ₂ SO ₄

This process is repeated until the manganese (II) sulfate has been largely converted to manganese (IV) oxide.

The mediator is used in particular in amounts of from 0.1 to 30% by weight, particularly preferably from 1 to 20% by weight, based on the composition used in the electrochemical oxidation, generally of a solution or suspension. The weight of the mediator refers only to the metal portion of the mediator, e.g. with manganese oxide only to those contained in the composition

Lot of manganese. To achieve high space-time yields as high as possible mediator concentrations are preferred; The amount of mediator is optionally limited by a limited solubility of its metal salts in the electrolyte and possibly too high conductivity.

The electrochemical oxidation (generation of the mediator) is preferably carried out in a solvent, in particular in water. The pH of the solution may be acidic or basic, it will be adjusted depending on the conditions required to generate the mediator. The system IVIn (I l / l 11) and Mn (ll / IV) is preferably generated at pH values between 0 and 5.

In addition to water, an inert solvent can also be used (co-solvent). Inert solvents are solvents which are not oxidized under the chosen conditions. Suitable examples include tertiary alcohols, ketones, esters, ethers, carbonates, amides, nitriles and halogen-containing hydrocarbons or fluorinated alcohols. Examples which may be mentioned are tert-butanol, ethyl acetate, acetone, methyl ethyl ketone, DMF, THF, dimethoxyethane, dichloromethane, chloroform, 1, 1, 2,2-tetrachloroethane, propylene carbonate, acetonitrile, 1, 1, 1, 3,3,3-hexafluoroisopropanol and hexafluoroacetone.

During electrochemical oxidation (generation of the oxidized form of the mediator) so-called conductive salts can be used. These have the task of depolarizing the electrodes. These are generally alkali metal, tetra (C 1 - to C 6 -alkyl) ammonium, preferably tri (C 1 - to C 6 -alkyl) -methylammonium salts. Suitable counterions are sulfate, bisulfate, alkyl sulfates, aryl sulfates, alkyl sulfonates, arylsulfonates, halides, phosphates, phosphonates, carbonates, alkyl phosphates, alkyl phosphonates, 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, methyltri-propylmethylammonium methylsulfates, or tetrabutylammonium tetrafluoroborate (TBABF4).

The use of so-called "lonic liquids" as conductive salt is likewise possible according to the invention; "lonic liquids" are known to the person skilled in the art.

In particular, strong mineral acids and sulfonic acids are suitable as conductive salts in the present invention. Examples are H2SO4, H3PO4., Methanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid. In the context of the present invention, the use of H2SO4 is usually preferred.

In the context of the present invention, a concomitant use of such conductive salts is not necessary, but if desired, not hindering or disadvantageous.

Suitable anodes in the process according to the invention are customary electrodes, eg Pb / PbC "2 electrodes, mixed metal oxide electrodes, such as RuO _x / TiO _x electrodes, DSA (dimensionally stable anodes) or diamond electrodes.

As cathode materials, for example, iron, steel, stainless steel, nickel, lead or noble metals such as platinum and graphite or carbon materials and diamond electrodes are considered.

The system is preferably diamond electrode as anode and cathode, diamond electrode as anode and nickel, stainless steel or steel as cathode, as well as lead or lead dioxide on lead as anode and steel, nickel or lead as cathode.

The mediator is generated at the anode and protons are reduced to hydrogen at the cathode. In a particular embodiment of the present invention, a diamond electrode is used in which the diamond layer is applied to a base body as the electrode material.

The diamond material used for the diamond layer is preferably doped with N, P and / or B (boron). Particularly preferred is the doping with B.

In a further preferred embodiment of the present invention, a diamond electrode is used in which the boron content in the diamond layer is between 10 ppm and 10000 ppm. Particularly preferred are boron contents between 10 ppm and 4000 ppm, most preferably between 100 ppm and 3000 ppm.

The main body preferably has one or more of the following materials: graphite, silicon, gold, titanium, molybdenum, niobium, or consists of one or more of the stated materials.

The thickness of the diamond coating is preferably in a range of 0.1 to 50 μm, more preferably 1 to 15 μm.

Diamond electrodes which can be used according to the invention are commercially available, for example, from the company Adamant Technologies under the type designation WD or from the company Condias under the designation Diachem® electrode.

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 or discontinuously with undivided flow cells.

Particularly suitable are bipolar switched capillary gap cells or Plattenstapelzellen in which the electrodes are designed as plates and are arranged plane-parallel (see Ullmann's Encyclopedia of Industrial Chemistry, 1999 electronic release, Sixth Edition, VCH Verlag Weinheim, Volume Electrochemistry, Chapter 3.5 Special cell designs and 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 20 to 200 mA / cm 2.

The temperatures are usually from -20 to 60 ⁰ C, preferably 0 to 60 ⁰ C. In general common carried out at atmospheric pressure. Higher pressures are preferably used when operating at higher temperatures to avoid boiling of the co-solvents. The organic compound to be oxidized can also be added in any form, for example in liquid form, as a solution or as a solid. Liquids are preferably added in bulk to the oxidized form of the mediator solution. Solids may also be used in bulk as a suspension or dissolved in an inert solvent.

The reaction of the compound to be oxidized can be carried out either in the electrolysis cell or in a separate reactor. The latter method is called "ex-cell method".

The organic compound to be oxidized can be used either in excess or in excess to achieve the highest possible selectivity to the desired product. To achieve the fullest possible conversion usually an excess of the oxidizing agent is required.

At the beginning of the current flow, the mediator is first activated, which then oxidizes the organic compound.

For this purpose, the required amount of charge is applied to achieve the desired oxidation state. The mediator solution obtained in this way is directly reacted further with the organic compound to be oxidized.

The process according to the invention results in oxidation to allyl position. Halogenic oxidants or chromates are not needed. High yields and product selectivities are achieved.

In particular, by the method according to the invention, e.g. β-ionone can be easily oxidized to 4-oxo-β-ionone or β-carotene easily to canthaxantin.

It can be worked to achieve high space-time yields even with high current densities.

Examples:

1. Oxidation of β-ionone to 4-oxo-β-ionone with electrochemically generated MnO 2 apparatus for the preparation of the mediator:

Cell Undivided flow cell with two electrodes arranged plane-parallel

Anode Circular diamond-coated niobium plate, 0 100 mm, thickness 2 mm, about 10 micron film thickness, about 1000 ppm boron doping B (commercially available DIACHEM electrode ^® of the company Condias, Itzehoe, Germany)

Cathode: Circular diamond-coated niobium plate, 0 100 mm, thickness 2 mm, about 10 micron film thickness, about 1000 ppm boron doping B (commercially available DIACHEM electrode ^® of the company Condias, Itzehoe, Germany)

Electrode distance: 3.2 mm active electrode area: 63.8 cm ²

Current density: 80 mA cm- ²

Voltage: 4V

Temperature: 15 ° C

Electrolyte: 59.2 g (0.35 mol) MnSO ₄ -H ₂ O, 1 17.6 g (1, 2 mol) of H ₂ SO ₄ 96%, 523.2 g of deionized water, batch size 700 g, according to a Mn concentration of 2.7 g / 100g of electrolyte.

Flow rate: 150 L h- ¹ "2 cell volumes S ^{" 1} Electrolysis time: 3.69 h corresponding to 2.0 F / mol Mn

During electrolysis under the conditions indicated, the electrolyte was pumped through the cell. After completion of the electrolysis, the cell was emptied and transferred the dark brown reaction mixture for further reaction in a 1-L stirred apparatus with Ultra-Turrax stirrer, temperature probe and Eisbadkühlung. Was added, 15.3 g (0.08 mol) beta-ionone and stirred for 20 min at 13,500 Umin-. ¹ By cooling with ice bath, the internal temperature is kept below 65 ° C. The reaction mixture became clear yellow-orange. The phases were separated and the aqueous phase was extracted twice more with 20 ml of methyl tert-butyl ether each time. The combined phases were dried and freed of the solvent. This gave 15.3 g of a brown oil as a crude product. By GC, a 4-oxo-β-ionone content of 65% was found, corresponding to a yield of 60%. Further purification can be carried out by means of standard laboratory methods, for example by column chromatography, distillation or crystallization. The spectroscopic data of the 4-oxo-β-ionone obtained in this way are in agreement with those from the literature.

2. Oxidation of ß-carotene to canthaxanthin with electrochemically generated

MnO ₂ apparatus for preparing the mediator:

Cell jacketed vessel with magnetic stirrer, temperature sensor and two plane-parallel electrodes Anode lead sheet 7 cm x 2 cm x 0.2 cm, immersion depth 5 cm

Cathode: lead sheet 7 cm x 2 cm x 0.2 cm, immersion depth 5 cm

Electrode distance: 10 mm active electrode area: 10.0 cm ²

Current density: 80 mA crrr ² voltage: 3-3.5 V.

Temperature: 15 ° C

Electrolyte: 5.1 g (0.0302 mol) MnSO ₄ -H ₂ O, 10.2 g (0.104 mol)

H ₂ SO ₄ 96% pure, 44.7 g of deionized water, batch size 60 g, corresponding to a Mn concentration of 2.8 g / 100 g of electrolyte.

Electrolysis time: 3.03 h, corresponding to 3.0 F / mol Mn

During electrolysis under the conditions indicated, the electrolyte in the cell was stirred. After completion of the electrolysis, the reaction mixture was heated to 52 ° C and a solution of 3.2 g (0.006 mol) ß-carotene in CHCb (50 mL) was added and the reaction mixture was stirred for 3 h at this temperature. For workup, the mixture was allowed to cool to room temperature, the phases were separated and the aqueous phase was washed twice more with CHCb. The combined phases were dried and freed of the solvent. 3.8 g of a foamy solidified red-brown solid were obtained. HPLC showed a canthaxanthin content of 22.5%, an echinone content (monooxidation product) of 14.0% and a β-carotene content of 13.4%.

Further purification may be carried out by laboratory standard methods, e.g. by column chromatography or crystallization.

Claims

claims 1. A process for the electrochemical oxidation of an organic compound on a carbon atom which is bonded directly to a non-aromatic double bond (alpha position to the double bond), characterized in that a mediator is used. 2. The method according to any one of claims 1, characterized in that the non-aromatic double bond is part of a non-aromatic ring system. 3. The method according to any one of claims 1 or 2, characterized in that the oxidation is selectively carried out only on one of the two alpha-C atoms and the other alpha-C atom is protected by substituents. 4. The method according to any one of claims 1 to 3, characterized in that it is an organic compound of formula I.

in which X represents a hydrogen atom or a hydroxyl group R 1, R 2 and R 3 independently of one another represent a C 1 to C 4 alkyl group and Y is an organic radical having at least 2 C atoms. 5. The method according to any one of claims 1 to 4, characterized in that the non-aromatic double bond is in conjugation with at least one further non-aromatic double bond of the radical Y. 6. The method according to any one of claims 1 to 5, characterized in that takes place at the carbon atom oxidation to a carbonyl group. 7. The method according to any one of claims 1 to 6, characterized in that ß-ionone is oxidized to 4-oxo-ß-ionone or ß-carotene to canthaxantine. 8. The method according to any one of claims 1 to 7, characterized in that the mediator is selected from a cerium, manganese or vanadium compound. 9. The method according to any one of claims 1 to 8, characterized in that the redox couple Mn 11 / Mn IV is used as a mediator. 10. The method according to any one of claims 1 to 9, characterized in that in the electrochemical oxidation Pb / Pbθ2 - electrodes or diamond electrodes are used. 1 1. A method according to any one of claims 1 to 10, characterized in that in the electrochemical oxidation no conductive salts are used.