EP1769103B1 - Electrochemical process for preparing cyclopropylbenzylamines - Google Patents

Abstract

Process for preparing primary amines having a cyclopropyl unit and a primary amino group bound to an aliphatic or cycloaliphatic carbon atom (amine A) by cathodically reducing oximes having a cyclopropyl unit or oxime derivatives in which the hydrogen atom in the oxime group has been replaced by an alkyl or acyl group (oxime O) at a temperature of from 50 to 100° C. in an essentially anhydrous electrolyte solution in a divided electrolysis cell.

Description

The present invention relates to a process for the preparation of primary amines having a primary amino group bonded to an aliphatic or cycloaliphatic carbon atom and a cyclopropyl moiety.

The preparation of primary amines by electrochemical reduction of oximes without further functional groups is out J. Indian Chem. Soc. 1991, 68, 95-97 known. In this case, a mercury-cathode was used and the electrolyte was cooled to about 5 ° C. In the preparation of primary amines containing Cyclopropyleinheiten, starting from corresponding oximes, it turned out, however, that when using relatively low reaction temperatures under these conditions in addition to the desired product of value undesirable by-products. One skilled in the art would expect that the formation of undesired by-products would tend to increase at higher reaction temperatures, since it is a generally accepted rule that the selectivity of a reaction decreases with increasing temperature and thus favors the formation of by-products.

BM PRASAD ET AL. in "Etectrochemica! Reduction of Ketoximes of some Cycloalkanones and 1,2-Diones" J INDIAN CHEM SOC, 1991, pages 95-97 , XP090057046 and N. AYYASWAMI, V. KRISHNAN in "Behavior of iximes at a nickel black cathode" JOURNAL OF APPLIED ELECTROCHEMISTRY, Vol. 14, No. 4, 1984, pages 557-559 , XPO09057148 disclose a process for the preparation of primary amines by electrochemical reduction of amines. Both BM PRASAD ET AL. but N. AYYASWAMI, V. KRISHNAN work at much lower temperatures and other amines A and oximes O, respectively.

It was therefore an object of the present invention to provide a process with which the amines according to the definition can be prepared electrochemically in high yields.

bei der der Phenylring gegebenenfalls durch Halogenatome oder C₁- bis C₄-Alkoxigruppen substituiert ist und es sich den Oximen O um Verbindungen
der allgemeinen (Formel IIa) handelt,

bei der der Phenylring gegebenenfalls durch Halogenatome oder C₁- bis C₄-Alkoxigruppen substituiert ist.Accordingly, a process has been found for the preparation of primary amines having a primary amino group attached to an aliphatic or cycloaliphatic C atom and a cyclopropyl moiety (amine A) which comprises oximes having a cyclopropyl moiety or oxime derivatives in which the hydrogen atom in the oxime group is replaced by an alkyl or acyl group (oxime O) in a divided electrolytic cell at a temperature of 50 to 100 ° C at the cathode, the water content in the catholyte and anolyte is less than 2% by weight and the amines A are compounds
the general formula la

in which the phenyl ring is optionally substituted by halogen atoms or C ₁ - to C ₄ -alkoxy groups and the oximes O are compounds
the general (formula IIa) acts,

in which the phenyl ring is optionally substituted by halogen atoms or C ₁ - to C ₄ alkoxy groups.

Optionally, the catholyte contains a solvent in addition to an amine formed in the course of the reaction A and an oxime. These are the inert solvents generally used in organic chemistry, such as dimethyl carbonate, propylene carbonate, tetrahydrofuran, dimethoxyethane, acetonitrile or dimethylformamide. The solvent used is preferably a C ₁ -C ₄ -alkyl alcohol. In combination with the solvents mentioned are also C ₅ - to C ₇ hydrocarbons such as hexane as a solvent.

For the preparation of the conductivity of the catholyte generally contains a mineral acid, preferably sulfuric acid or an alkali (C _{1 to} C ₄ ) -alkylalkoholat, preferably sodium methoxide.

In general, an electrolyte salt is added to the anolyte and optionally also to the catholyte (in addition to one of the above-mentioned conductivity-producing agents). These are generally alkali metal, tetra (C ₁ -C ₆ -alkyl) ammonium, preferably tri (C ₁ -C ₆ -alkyl-methylammonium salts. The counterions used are sulfate, hydrogensulfate, alkyl sulfates, aryl sulfates, halides, phosphates, Carbonates, alkyl phosphates, alkyl carbonates, nitrate, alcoholates, tetrafluoroborate, hexafluorophosphate or perchlorate into consideration.

Preference is given to methyltributylammonium methylsulfates (MTBS), methyltriethylammonium methylsulfate or methyltri-propylmethylammonium methylsulfates.

The water content in the catholyte and anolyte is generally less than 2, preferably less than 1 wt.%, Particularly preferably less than 0.5 wt.%. It should be noted that in the reduction of the oxime O to the amine A water is formed in stoichiometric amounts. If the batchwise reaction of the process is carried out with sufficiently high dilution of the starting product and the catholyte and anolyte have a water content of less than 0.1% by weight at the beginning of the reaction, the water formed during the reaction is generally unnecessary to remove the electrolyte. Otherwise, the water content of the electrolyte can be determined by conventional methods, e.g. be lowered by distillation.

The process according to the invention can be carried out in all customary divided types of electrolysis cell in order to be able to exclude within the scope of the process according to the invention that reactants such as products undergo chemical side reactions by the cathodic process. Preferably, one works continuously in divided flow cells.

Divided cells with plane-parallel electrode arrangement are preferably used. As separation media can ion exchange membranes, microporous membranes, diaphragms, filter fabric of non-electron-conducting materials, glass frits, and porous ceramics are used. Preferably ion exchange membranes, in particular cation exchange membranes are used. These conductive membranes are commercially available, e.g. available under the tradename Nafion® (E.T. DuPont de Nemours and Company) and Gore Select® (W.L. Gore & Associates, Inc.).

As cathodes, it is preferable to use those in which the cathode surface is formed of a high hydrogen overvoltage material, e.g. of lead, zinc, tin, nickel, mercury, cadmium, copper or alloys of these metals or glassy cabon, graphite or diamond.

Particularly preferred are diamond electrodes, such as in the EP-A-1036863 are described.

In principle, all conventional materials are suitable as anodes, preferably those which are also referred to as cathode materials. In the acidic anolyte, preference is given to using platinum, diamond, glassy carbon or graphite anodes or the dimensionally stable anodes (DSA) known to the person skilled in the art. If the anolyte is basic, preferably stainless steel is used.

The anodic reaction can be chosen freely, preferably the C ₁ - to C ₄ -alcohol used as solvent is oxidized there. When methanol is used, methyl formate, formaldehyde dimethyl acetal or dimethyl carbonate are formed. For example, a sulfuric acid solution diluted with a C ₁ -C ₄ -alcohol is used for this purpose.

The current densities at which the process is carried out are generally 1 to 1000, preferably 10 to 100 mA / cm ² . In general, working at atmospheric pressure. Higher pressures are preferably used when operating at higher temperatures to avoid boiling of the starting compounds or solvents.

After completion of the reaction, the electrolyte solution is worked up by general separation methods. For this purpose, the catholyte 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 or by chromatography.

Experimental part

example 1

Apparatus:

Electrolysis system with catholyte and anolyte circuit and two split-cell electrolysis cells connected in series

Anode:

2 graphite anodes, effective area 300 cm ² each

Cathode:

2 lead cathodes, effective area per 300 cm ²

Membrane:

proton-conducting perfluorinated membrane having sulfonic acid groups, e.g. Nafion 324 from DuPont

Distance of electrode ↔ membrane:

6 mm

Current density:

3.4 A / dm2

Tension:

20-40 v

Temperature:

55 ° C

Composition anolyte:

979.2 g MeOH, 20.8 g H2SO4, 96% pure

Composition catholyte:

5000 g of MeOH, 400 g of sodium methoxide sol., 30% in MeOH, 600 g of cyclopropylphenylmethanone oxime 1

Flow rate:

150 - 200 hours

During the electrolysis under the conditions indicated, the anolyte and catholyte were pumped through the respective half-cells for 24 h (corresponding to an amount of charge of 5 F / mol 1). The gas chromatographic analysis of the reaction yield showed 95.1 FI .-% of the desired value product 2, 0.10% of the ring-opened compound 3, 0.82% starting material 1 and 3.18% high boilers.

Example 2

Apparatus:

Electrolysis cell with catholyte and anolyte circulation

Anode:

Graphite, effective area 35 cm ²

Cathode:

Lead, effective area 35 cm ²

Membrane:

proton conductive perfluorinated membrane having sulfonic acid groups, e.g. Nation 117 of the company DuPont

Current density:

3.4 A / dm2

Tension:

15 - 20 V

Temperature:

40 ° C

Composition anolyte:

117.5 g MeOH, 2.5 g H2SO4, 96%

Composition catholyte:

94.0 g MeOH, 1.0 g H2SO4, 96%, 5 g cyclopropylphenylmethanone oxime 1

During the electrolysis under the conditions indicated, the anolyte and catholyte were pumped through the respective half-cells for 4.11 h (corresponding to an amount of charge of 6 F / mol 1). The gas chromatographic analysis of the reaction yield showed 83.3 area% of the desired value product 2, 1.3% of the ring-opened compound 3 and 15.6% high and medium boilers.

Example 3 (for comparison)

Apparatus.

Electrolytic cell with catholyte and anolyte circulation

Anode:

Graphite, effective area 300 cm ²

Cathode:

Lead, effective area 300 cm ²

Membrane:

proton-conducting perfluorinated membrane having sulfonic acid groups, e.g. Nafion 324 from DuPont

Current density:

3.4 A / dm ²

Tension:

14 - 33 v

Temperature:

40 ° C

Composition anolyte:

783 g of MeOH, 17 g of H ₂ SO ₄ , 96% pure

Composition catholyte:

2600 g of MeOH, 100 g of NaOMe, 30% in MeOH, 300 g of cyclopropylphenylmethanone oxime 1

During the electrolysis under the specified conditions, the anolyte and catholyte were pumped through the respective half-cells for 27.6 hours (corresponding to an amount of charge of 6.5 F / mol 1). The gas chromatographic analysis of the reaction yield yielded 77.3% by area of the desired product of value 2, 2.0% of unreacted oxime 1 and 20.7% of high and medium boilers.

Claims (6)

1. A process for preparing primary amines having a cyclopropyl unit and a primary amino group bound to an aliphatic or cycloaliphatic carbon atom (amine A) by cathodically reducing oximes having a cyclopropyl unit or oxime derivatives in which the hydrogen atom in the oxime group has been replaced by an alkyl or acyl group (oxime O) at a temperature of from 50 to 100°C in a divided electrolysis cell, wherein the water content of the catholyte and anolyte is less than 2% by weight and the amines A are compounds of the general formula Ia,

   

   in which the phenyl ring may be substituted by halogen atoms or C₁-C₄-alkoxy groups and
   the oximes 0 are compounds of the general formula IIa,

   

   in which the phenyl ring may be substituted by halogen atoms or C₁-C₄-alkoxy groups.
2. The process according to Claim 1, wherein the catholyte comprises an amine A and an oxime 0 and also a C₁-C₄-alkyl alcohol as solvent.
3. The process according to Claims 1 to 2, wherein the catholyte comprises a mineral acid or an alkali metal (C₁-C₄)alkoxide.
4. The process according to Claims 1 to 3, wherein the cathode surface is formed by a material having a high hydrogen overvoltage.
5. The process according to Claims 1 to 4, wherein the cathode surface is formed by lead, zinc, tin, nickel, mercury, cadmium, copper or alloys of these metals or glassy carbon, graphite or diamond.
6. The process according to Claims 1 to 5, wherein the water content of the catholyte is less than 2% by weight.