EP0370866A1 - Aldehydes electrosynthesis process - Google Patents

Abstract

The process for the electrosynthesis of an aldehyde, according to the invention, is carried out by electrolysis, in a cell comprising only a single compartment, of an organic halide and of an N,N-disubstituted formamide such as dimethylformamide, followed by hydrolysis of the reaction mixture. The anode is made of a metal chosen from the group consisting of the reducing metals and their alloys, preferably zinc, aluminum or magnesium. The cathode, which is inert, is preferably covered with an electrolytic deposit of zinc, cadmium, lead or tin. Aldehydes are compounds which are commonly employed in many fields of the chemical industry, especially in perfumery, agricultural chemistry and pharmacy.

Description

The invention relates to a process for the electrochemical synthesis of an aldehyde by electrolysis in a cell provided with electrodes of an organic halide and of an N, N-disubstituted formamide, then hydrolysis of the reaction medium.

Aldehydes are compounds commonly used in many fields of the chemical industry, notably in perfumery, agrochemicals and pharmacy.

There are many methods of synthesizing aldehydes. Among these, mention may be made of those for which the aldehyde is obtained by electrolysis, in a cell provided with electrodes, an organic halide and an N, N-disubstituted formamide, then hydrolysis of the reaction medium.

CASARDO and GALLARDO in Electrochimica Acta, Vol. 32, n ° 8, pp. 1145-1147, (1987) describe the synthesis of traces of benzaldehyde during the electrolysis of bromo or iodobenzene solutions in dimethylformamide (DMF). The cell has 2 separate compartments, anodic and cathodic. The cathode is made of mercury and the inert anode is made of graphite.

VIEIRA and PETERS in J. Org. Chem., Vol. 51, n ° 8, pp. 1231-1239, (1986) describe the synthesis of pivalic aldehyde during the electrolysis of a solution of tert-butyl bromide in DMF. The yields are very low, less than 14%. The cell has 2 separate compartments, anodic and cathodic. The cathode is made of mercury and the inert anode is made of carbon.

The authors also teach that they could not obtain, under the same conditions, the formation of aldehydes from primary or secondary alkyl halides.

The Applicant has discovered that, completely unexpectedly, good yields are obtained, even from primary or secondary alkyl halides, when the cell has only one compartment and when an anode consumable in a metal is used chosen from the group consisting of reducing metals and their alloys.

The method according to the invention, compared with the closest aforementioned state of the art, has, in addition to a considerable improvement in yield and a widening of the field of application, a certain number of other advantages, the main ones of which are:
a simpler implementation since the process is carried out in an electrolysis cell comprising only one compartment, without diaphragm or sintered, which is very important at the industrial stage,
- a very much higher halide concentration,
- a higher current intensity, of the order of several amperes per dm²,
- the possibility of using a very low support electrolyte concentration, of the order of 10⁻²M,
- the use of solid electrodes limiting the risks of pollution by heavy metals such as mercury.

The electrolysis cell is a cell comprising only one compartment, that is to say for which there is no comparison separate anode and cathode tents. This possibility of using such a cell is an important advantage, as has already been mentioned.

The anode is consumable, that is to say it is consumed during the electrochemical reaction of which it is the seat. This is the reason why such processes are sometimes called "soluble anode". The anode is made of a metal chosen from the group consisting of reducing metals and their alloys, that is to say any alloy containing at least one reducing metal.

Preferably, the anode is made of a reducing metal chosen from the group consisting of magnesium, aluminum, zinc and their alloys, that is to say any alloy containing at least one of the three metals mentioned above, namely zinc, aluminum and magnesium. This anode can have any shape and in particular all the classic forms of metal electrodes such as twisted wire, flat bar, cylindrical bar, renewable bed, balls, fabric, grid. Preferably, a cylindrical bar of diameter adapted to the dimensions of the cell is used.

The cathode is any metal such as stainless steel, gold, nickel, platinum, copper, aluminum, iron or carbon such as, for example, vitreous carbon or graphite. It is preferably formed by a grid or a cylindrical plate arranged concentrically around the anode.

The Applicant has discovered that, unexpectedly, the efficiency is considerably improved when the cathode is covered with an electrolytic deposit of a metal M chosen from the group consisting of zinc, cadmium, lead and tin.

The electrodeposition of the metal M on the cathode, prior to the electrosynthesis of the aldehyde, can be carried out according to various methods, in particular those described in Examples 14 to 38.

The electrodes are supplied with direct current via a stabilized power supply.

dans laquelle R¹ et R², identiques ou différents, représentent une chaîne alipha­tique ou aromatique, substituée ou non substituée, de préférence soit une chaîne alkyle comportant 1 à 8 atomes de carbone, soit un cycle phényle substitué ou non substitué, ou bien encore R¹ et R² forment un cycle.Preferably, according to the invention, the aldehyde corresponds to the general formula RCHO in which R represents an organic radical, the organic halide corresponds to the general formula RX in which R has the abovementioned meaning and X represents an atom of halogen, preferably chlorine or bromine, and the N, N-disubstituted formamide corresponds to the general formula

in which R¹ and R², identical or different, represent an aliphatic or aromatic chain, substituted or unsubstituted, preferably either an alkyl chain containing 1 to 8 carbon atoms, or a substituted or unsubstituted phenyl ring, or alternatively R¹ and R² form a cycle.

Preferably, R represents an aliphatic, arylaliphatic, aromatic, alkylaromatic or heterocyclic organic radical, substituted or unsubstituted, preferably an alkyl radical or a phenyl group, substituted or unsubstituted. Obviously, when R carries various substituents, these must be more difficult to reduce than the R-X bond.

Particularly preferably the formamide is DMF. As examples of other formamides, mention may be made of N, N-dialkylformamides and N-phenyl N-methylformamide (N-methylformanilide).

It is also possible to use a mixture of several formamides corresponding to the general formula mentioned above.

dans lequel R, R¹ et R² ont la signification précitée.The process which is the subject of the present invention can be represented by the following reaction scheme:

wherein R, R¹ and R² have the above meaning.

The hydrolysis of the reaction medium is for example carried out with an acidic aqueous solution.

Preferably, in the context of the present invention, the formamide N, N-disubstituted, in addition to its role as reagent, also plays the role of solvent. This is particularly the case when using DMF. It is then not necessary to use another solvent. Electrolysis can however be carried out in the presence of a co-solvent chosen from aprotic solvents with low electrophilicity, such as, for example, tetramethylurea (TMU) and tetrahydrofuran (THF).

When, under the conditions of electrosynthesis, the formamide N, N-disubstituted is in a physical state such that it can no longer properly play its role of solvent, the presence of such a slightly electrophilic aprotic solvent is then recommended.

The concentration of the reactants is preferably chosen so as to ensure a very large molar excess of formamide, since the latter also preferably plays the role of solvent.

The concentration of the organic halide in the reaction medium is generally between 0.05 and 2 mol / l.

The reaction medium is made conductive by a slightly reducible support electrolyte. Mention may be made, for example, of salts whose anion is a halide, a carboxylate, a fluoroborate, a perchlo spleen or a hexafluorophosphate and the cation a quaternary ammonium, aluminum, zinc, sodium, potassium, calcium, lithium, a tetraalkylphosphonium, as well as mixtures of these salts. Tetramethylammonium fluoroborate or tetrabutylammonium bromide is preferably used.

Before electrolysis, the solution is oxygenated by bubbling an inert gas, nitrogen or argon for example.

The reaction temperature is preferably between 0 and 80 ° C, for example room temperature.

During the entire duration of the electrolysis, the solution is stirred, maintained under an inert atmosphere, of nitrogen or argon for example, and cooled if necessary to maintain its temperature between 0 and 80 ° C. preferably.

The current density on the cathode is preferably chosen between 0.2 and 20 A / dm².

We generally operate at constant intensity, but we can also operate at constant voltage, with controlled potential, or with variable intensity and potential.

The duration of the electrolysis is preferably chosen so that the amount of current involved corresponds approximately to 2 Faraday (193 10³C) per mole of organic halide.

One can also follow the evolution of the organic halide concentration by analysis of aliquot samples and stop the electrolysis as soon as the desired transformation rate is reached.

After electrolysis, the reaction medium is hydrolyzed with an acidic aqueous solution, for example dilute hydrochloric acid, then extraction is carried out with an organic solvent. After drying and evaporation of the extraction solvent, the aldehyde is obtained which is identified and assayed according to conventional methods of analysis, after optional purification by passage over a column of silica for example.

In the particular case where a cathode covered with an electrolytic deposit of a metal M as defined above is used, it is possible, when M represents cadmium, lead or tin, to directly introduce the metal M to be deposited on the cathode in the form of salt, cadmium bromide, lead acetate or tin chloride for example, in the organic halide and N, N-disubstituted formamide mixture. At the start of electrolysis, the metal M is deposited on the cathode. In order to improve the adhesion and the quality of the deposit, it is possible, at the start of electrolysis, to use a current of lower intensity.

When the organic halide is very reactive, which is the case for example for allylic or benzylic halides, the yield is improved by adding the organic halide gradually into the reaction medium during electrolysis.

The invention is illustrated by the nonlimiting examples which follow.

To carry out these examples, a conventional electrolysis cell is used, comprising only one compartment.

The upper part of the cell is made of glass and is equipped with 5 tubes, including a central one, allowing the arrival and the exit of argon used as inert gas, the possible samples of solution during electrolysis, the addition of reagents, electrical passages.

The lower part consists of a stopper fitted with a seal, screwed onto the upper glass part.

The total volume of the cell is close to 45 cm³ and its volume uti the neighbor of 35 cm³.

The anode is a cylindrical bar with a diameter close to 1 cm, made of zinc, magnesium or aluminum according to the tests. It is introduced into the cell through the central tube and is thus located approximately in axial position relative to the cell.

The cathode consists of a metallic cylindrical grid arranged concentrically around the anode. The working surface of the cathode is around 20 cm².

The cell is immersed in a thermostatic bath set to the chosen temperature.

During the electrolysis the reaction medium is stirred, for example by means of a magnetic bar.

Examples 1 to 12

The solution to be electrolyzed, consisting of:
- organic halide,
- the formamide N, N-disubstituted or the mixture of formamides N, N-disubstituted,
- possibly the co-solvent,
the support electrolyte, tetramethylammonium fluoroborate at a concentration of 5 × 10 -2 M except for Example 7 for which the support electrolyte is tetrabutylammonium bromide at the concentration of 10⁻²M.

This mixture is degassed by bubbling argon, then it is maintained under an argon atmosphere.

After constant intensity electrolysis for a corresponding period dant at 3 Faraday (290 10³C) per mole of organic halide, the reaction medium is hydrolyzed with a 1N aqueous hydrochloric acid solution and then extracted with diethyl ether.

The organic phase is then separated and washed with water.

After drying and evaporation of the solvents, the aldehyde obtained is purified by chromatography on a silica column and then identified according to conventional methods of analysis, in particular by infrared (IR), mass (SM) and nuclear magnetic resonance (NMR) spectrometries. ).

The nature of the starting organic halide, that of the aldehyde formed and the corresponding mass yield of isolated pure aldehyde are shown in Table 1 for each example.

The organic halide concentration is 0.5 M for Examples 1, 3 to 9, 12 and 0.125 M for Example 2.

For examples 10 and 11, CF₃Br being a gas, it is introduced by bubbling into the reaction medium under a pressure of 10⁵Pa (1 bar).

The cathode is made of nickel for examples 10 and 11, of stainless steel for examples 1 to 6, 8, 9 to 12, of lead for example 7.

The anode is made of zinc for example 10, of aluminum for examples 1 to 4, 6 to 9 and 12.

The volume of formamide, or mixture of formamides, is 36cm³. This volume includes the co-solvent when it is present.

The formamide is DMF for examples 1 to 5 and 7 to 12, a 1/1 mixture by volume of DMF / N-methylformanilide for example 6.

Examples 2 and 4 are carried out in the presence of a co-solvent. For example 2 the co-solvent is THF and the volume ratio DMF / THF is 2/1 respectively. For example 4 the co-solvent is TMU and the volume ratio DMF / TMU is respectively 1/1.

The current density on the cathode is 2A / dm² for examples 1, 2, 7 to 11, 1.5 A / dm² for example 12, 1 A / dm² for examples 3 and 4 and 0.5 A / dm² for examples 5 and 6.

The reaction temperature is 25 ° C for Examples 1 to 9 and 0 ° C for Examples 10 to 12.

For Examples 10 and 11, the trifluoroacetaldehyde is isolated in the form of a hydrate and the yield indicated in Table 1 is a faradaic yield calculated from the amount of electricity used.

Example 13

The experimental conditions for this example are the same as those of Example 1 but the initial concentration of benzyl chloride is 0.125 M. After electrolysis corresponding to the passage of 2 Faraday (193 10³C) per mole of benzyl chloride, we add an amount of benzyl chloride equal to that present at the start. Electrolysis is then continued until the total duration thereof corresponds to 3 Faraday (290 10³C) per mole of benzyl chloride used. The yield of isolated pure aldehyde is 50%.

Examples 14 to 38

For these examples, the cathode, made of stainless steel or nickel, is covered with an electrolytic deposit of a metal M.

The electrodeposition of metal M on the cathode, prior to the electrosynthesis of the aldehyde, was carried out according to several methods:

Method A:

In DMF containing tetrabutylammonium bromide as a support electrolyte at the concentration of 10⁺²M, MBr₂ is added at a concentration of the order of 5 10⁻²M to 10-¹M. The cell is equipped with a metal anode M and a current of 0.1 to 0.2 A is imposed for 0.5 to 1 hour, which makes it possible to transport M from the anode to the cathode.
The anode M is then replaced by a magnesium bar and the electrolysis is continued at constant intensity for the time necessary for the almost complete exhaustion of the M²⁺ ions present in the solution. The organic halide is then added to this solution.

Method B:

In DMF containing tetrabutylammonium bromide as support electrolyte at the concentration of 10⁻²M, MBr₂ is added at a concentration of the order of 5 10⁻²M to 10⁻¹M. The cell is equipped with a magnesium anode and a current of 0.1 to 0.2 A is imposed for the time necessary for the electrodeposition of the M²⁺ ions on the cathode. The organic halide is then added.

Method C:

When M is cadmium, lead or tin, we can operate in a single step. In DMF containing tetrabutylammonium bromide as support electrolyte at the concentration of 10⁻²M, CdBr₂, Pb (CH₃CO₂) ₂ or SnCl₂ are added, at a concentration of the order of 5 10 5² to 10⁻¹M, as well as organic halide.
The cell is equipped with a magnesium anode and a constant intensity current is imposed.
The electrodeposition of cadmium, lead or tin on the cathode precedes the electrosynthesis of the aldehyde.

Method D:

The cathode coated according to one of the aforementioned methods A, B or C then having served for the electrosynthesis of an aldehyde according to the invention is reused without modification in a new electrosynthesis of aldehyde with a magnesium anode, in DMF medium containing tetrabutylammonium bromide at a concentration of 10⁻²M as a support electrolyte.

For all these examples 14 to 38, electrosynthesis is carried out at ambient temperature, by imposing a current of constant intensity such that the current density on the cathode is 1 A / dm².

The duration of the electrolysis is chosen so as to employ 2.1 Faraday (203 10³ C) per mole of organic halide.

Before electrolysis, the reaction medium is degassed for barbota argon, then the medium is maintained under an argon atmosphere.

After the electrolysis, the medium is hydrolyzed, then the aldehyde formed is isolated, purified, identified and assayed according to the method described for Examples 1 to 14.

For example 37, the aldehyde is recovered in the form of a hydrate.

It is also possible to assay the unreacted organic halide and the aldehyde formed by gas chromatography (GC) from a sample of an aliquot of the solution after acid hydrolysis (HCl 6 N) and extraction. with diethyl ether.
The assay of the unreacted organic halide allows the calculation of the conversion rate of this halide.

The following table 2 specifies for each example the nature and the concentration in DMF of the organic halide, the nature of the cathode as well as the method used for electrodepositing the metal M.

Table 3 below specifies for each example the conversion rate of the organic halide as well as the nature and the yield with respect to the starting organic halide, of the aldehyde formed. For certain examples, the yield of isolated pure aldehyde is also indicated in brackets.

Example 39

The operation is carried out according to the general conditions relating to examples 14 to 38 but:
- The current density on the cathode is 0.1 A / dm².
- We use a stainless steel cathode coated with an electrolytic deposit of cadmium according to method D.
- The reaction medium is a 75/25 mixture by volume of N-methylformanilide and TMU respectively, containing tetrabutylammonium bromide as support electrolyte at the concentration of 10⁻²M and pCF₃C₆H₄Cl as organic halide at the concentration of 0.50 mol / l.

The conversion rate of the organic halide is 100%. PCF₃C₆H₄CHO is obtained with a yield of 15%.

Example 40

After degassing by bubbling argon and keeping the cell under an argon atmosphere, a solution of 9 g of parachlorotrifluorotoluene, 200 mg of tetrabutylammonium bromide and 500 mg of anhydrous cadmium bromide in 35 ml of DMF is electrolyzed. a current of intensity 0.1 A then for 5 h and 30 min under a current of intensity 0.5 A while maintaining the temperature of the reaction medium at around 40 ° C.
The anode is made of magnesium and the cathode made of stainless steel.
The reaction medium is then treated as in Examples 14 to 38. Trifluoromethylbenzaldehyde is obtained with a yield of 85%. Note in this example the particularly high concentration of organic halide (about 1.5 M).

Claims (9)

1. Process for the electrosynthesis of an aldehyde by electrolysis in an electrolytic cell provided with electrodes, an organic halide and an N, N-disubstituted formamide, then hydrolysis of the reaction medium, characterized in that the cell does not has only one compartment and in that an anode consumable in a metal chosen from the group consisting of reducing metals and their alloys is used. 2. Method according to claim 1 characterized in that the anode is made of a reducing metal chosen from the group consisting of magnesium, aluminum, zinc and their alloys. 3. Method according to any one of the preceding claims, characterized in that the aldehyde corresponds to the general formula RCHO in which R represents an organic radical, in that the organic halide corresponds to the general formula RX in which R has the aforementioned meaning and X represents a halogen atom, preferably chlorine or bromine and in that the N, N-disubstituted formamide corresponds to the general formula

in which R¹ and R², identical or different, represent an aliphatic or aromatic chain, substituted or unsubstituted, preferably either an alkyl chain containing 1 to 8 carbon atoms or a substituted or unsubstituted phenyl ring, or alternatively R¹ and R² form a cycle. 4. Method according to claim 3 characterized in that R represents an aliphatic, arylaliphatic, aromatic, alkylaromatic or heterocyclic organic radical, substituted or unsubstituted, preferably an alkyl radical or a phenyl group, substituted or unsubstituted. 5. Method according to any one of the preceding claims, characterized by the additional presence of an organic solvent in the reaction medium. 6. Method according to any one of the preceding claims, characterized in that the cathode is covered with an electrolytic deposit of a metal M chosen from the group consisting of zinc, cadmium, lead and tin. 7. Method according to any one of claims 1 to 5 characterized by the additional presence of a cadmium, lead or tin salt in the reaction medium. 8. Method according to any one of the preceding claims, characterized in that the concentration of the organic halide is between 0.05 and 2 mol / l. 9. Method according to any one of claims 1 to 7 characterized in that the organic halide is gradually added to the reaction medium during electrolysis.