EP0638665B1 - Process for the preparation of benzaldehyde dialkyl acetals - Google Patents

Description

in der R¹ C₁-C₆-Alkyl und R² C₁-C₆-Alkyl, C₁-C₆-Alkoxy, Halogen, Cyano oder Carboxyalkyl mit 1 bis 6 Kohlenstoffatomen in der Alkylgruppe bedeutet und n eine ganze Zahl von 1 bis 3 ist, wobei die Reste R² im Falle von n > 1 gleich oder verschieden sein können, durch elektrochemische Oxidation substituierter Toluolverbindungen der allgemeinen Formel II

This invention relates to an improved process for the preparation of benzaldehyde dialkyl acetals of the general formula I

in which R ^{1 is} C ₁ -C ₆ alkyl and R ^{2 is} C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, halogen, cyano or carboxyalkyl having 1 to 6 carbon atoms in the alkyl group and n is an integer from 1 to 3, where the radicals R ² in the case of n> 1 may be the same or different, by electrochemical oxidation of substituted toluene compounds of the general formula II

Process products I serve as intermediates for the production of crop protection agents and pharmaceuticals.

DE-A 41 06 661 relates to a process for the preparation of substituted 2-methylbenzaldehyde dialkyl acetals. According to the teaching of this document, the process can be carried out continuously or discontinuously at normal pressure or elevated pressure. However, the selectivities to be achieved according to the teaching of this publication are not sufficient in all cases for large-scale practice of the process.

EP-12 240 relates to the electrochemical oxidation of optionally substituted toluene compounds to the corresponding benzaldehyde dialkyl acetals in the presence of alkanols and of conductive salts which are derived from sulfuric acid or phosphoric acid. In a continuous embodiment of the process, the reaction mixture can be worked up by distillation to give the process product and the by-products isolated in this way the oxidation level can be returned. By-products that can interfere with the oxidation reaction are subjected to hydrogenation before being recycled. The examples show that the discontinuous electrooxidation of p-tert-butyltoluene with a selectivity of 63%, with hydrogenation treatment of the by-products with up to 92% selectivity with a conversion of 26% leads to p-tert-butylbenzaldehyde dialkyl acetal. However, the conversion achieved in this way is unsatisfactory since large quantities of the unreacted starting material either have to be discarded or have to be recycled. The teaching of this document, to lower the current density and thereby increase the selectivity of the reaction, lowers the space-time yield of the process and thereby reduces its economy.

The object was therefore to provide a process which allows the continuous electrochemical production of benzaldehyde dialkyl acetals both with high conversions and with high selectivities.

A)

bei diskontinuierlicher Fahrweise das beim Entspannen freigesetzte Gas von der Reaktionslösung abtrennt, die Reaktionslösung mindestens einmal in die Elektrolysezelle zurückführt, elektrolysiert, entspannt und von freigesetztem Gas abtrennt und anschließend auf das Produkt aufarbeitet, oder

B)

bei kontinuierlicher Fahrweise einen Teil der Reaktionslösung auf das Produkt aufarbeitet, den verbleibenden Teil der Reaktionslösung mit einer dem entnommenen Teil entsprechenden Menge der ursprünglich eingesetzten Reaktionslösung versetzt, in die Elektrolysezelle zurückführt, elektrolysiert und entspannt.

Accordingly, the process defined above was found, which is characterized in that a substituted toluene compound II is oxidized in the presence of an alkanol R ¹ -OH and an auxiliary electrolyte in an electrolysis cell, the reaction solution thus obtained is vented outside the electrolysis cell to a pressure of 10 mbar is up to 10 bar lower than the pressure in the electrolysis cell, and

A)

in the case of a discontinuous procedure, the gas released during the expansion is separated from the reaction solution, the reaction solution is returned to the electrolysis cell at least once, electrolyzed, expanded and separated from the released gas and then worked up on the product, or

B)

in a continuous mode of operation, some of the reaction solution is worked up to the product, the remaining part of the reaction solution is mixed with an amount of the originally used reaction solution corresponding to the removed part, returned to the electrolytic cell, electrolyzed and relaxed.

The method according to the invention can be illustrated as follows:

R¹-

C₁-C₆-Alkyl, vorzugsweise C₁-C₄-Alkyl, vor allem Methyl und Ethyl;

R²-

C₁-C₆-Alkyl wie Methyl, Ethyl, n-Propyl, iso-Propyl, n-Butyl, tert.-Butyl, tert.-Amyl, n-Hexyl, vorzugsweise Methyl, Ethyl, iso-Propyl und tert.-Butyl;

• - C1-C4-Alkoxy wie Methoxy, Ethoxy, n-Propoxy, tert.-Butoxy, vorzugsweise Methoxy, Ethoxy und tert.-Butoxy;
• - Halogen wie Fluor, Chlor, Brom und Jod, vorzugsweise Chlor;
• - Cyano;
• - Carboxyalkyl, wobei die Alkylgruppen 1 bis 6 Kohlenstoffatome tragen, wie Carboxymethyl und Carboxyethyl;
• - n ist eine ganze Zahl von 1 bis 3, vorzugsweise 1.

The starting compounds II are known or they can be obtained by known methods. The variables have the following meanings:

R ¹ -

C ₁ -C ₆ alkyl, preferably C ₁ -C ₄ alkyl, especially methyl and ethyl;

R ² -

C ₁ -C ₆ alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, tert-amyl, n-hexyl, preferably methyl, ethyl, isopropyl and tert.- Butyl;

• C1-C4-alkoxy such as methoxy, ethoxy, n-propoxy, tert-butoxy, preferably methoxy, ethoxy and tert-butoxy;
• - Halogen such as fluorine, chlorine, bromine and iodine, preferably chlorine;
• - cyano;
• Carboxyalkyl, the alkyl groups having 1 to 6 carbon atoms, such as carboxymethyl and carboxyethyl;
• - n is an integer from 1 to 3, preferably 1.

With regard to their use as intermediates for crop protection agents and pharmaceuticals, those of the formula III are preferred among the compounds II in which the substituent R ^{3 is} a C ₁ -C ₆ -alkyl radical or C ₁ -C ₄ -alkoxy radical.

• 4-Methylbenzaldehyddimethylacetal
• 4-Methylbenzaldehyddiethylacetal
• 4-Ethylbenzaldehyddimethylacetal
• 4-Isopropylbenzaldehyddimethylacetal
• 4-n-Butylbenzaldehyddiethylacetal
• 4-tert.-Butylbenzaldehyddimethylacetal
• 4-Methoxybenzaldehyddimethylacetal
• 4-Ethoxybenzaldehyddimethylacetal
• 4-tert.-Butoxybenzaldehyddimethylacetal

The preparation of the following compounds is particularly preferred:

• 4-methylbenzaldehyde dimethyl acetal
• 4-methylbenzaldehyde diethylacetal
• 4-ethylbenzaldehyde dimethyl acetal
• 4-isopropylbenzaldehyde dimethyl acetal
• 4-n-Butylbenzaldehyde diethylacetal
• 4-tert-butylbenzaldehyde dimethyl acetal
• 4-methoxybenzaldehyde dimethyl acetal
• 4-ethoxybenzaldehyde dimethyl acetal
• 4-tert-butoxybenzaldehyde dimethyl acetal

The process according to the invention can be carried out batchwise or continuously. Both embodiments have in common that the electrochemical oxidation of the starting compound II is carried out in the electrolysis cell and the resulting reaction solution is expanded to a pressure which is 10 mbar to 10 bar lower than the pressure in the electrolysis cell. The electrolysis cell preferably has an overpressure, based on normal pressure, of 0.1 to 6 bar. This pressure can preferably be built up in the electrolysis cell by means of a pump, but can also be generated by an inert gas such as nitrogen. After the oxidation step, the reaction solution is preferably let down to normal pressure.

A) Discontinuous embodiment

In a discontinuous embodiment of the invention, gas released during the expansion of the reaction solution after the electrolysis, which is predominantly hydrogen discharged from the electrolysis cell, is separated off. The reaction solution is then returned to the electrolysis cell, electrolyzed and then relaxed. This sequence of process steps is referred to below as cycles. It has proven to be advantageous to expose the reaction solution to a large number of cycles, as a result of which a higher yield can be achieved economically than in only two cycles. 20 to 1000 cycles are preferred, particularly preferably 100 to 800. The oxidation of the starting compound II in one cycle is generally not carried out until complete conversion. Depending on the number of cycles, the turnover is generally 0.1 to 5% of the theoretical turnover. When the desired degree of oxidation of the starting compound II has been reached, the reaction solution is worked up onto the product. This is done in a manner known per se, predominantly by distillation. If a solvent is present in the reaction solution, it is distilled off. If neutral salts are used as auxiliary electrolyte, these can then be filtered off before the acetal I is distilled. Solvents, electrolyte and unreacted starting compound can be used again in further process approaches.

B) Continuous embodiment

The continuous embodiment of the present invention is preferred. After expansion of the reaction solution, which - as described under A) - is generally not electrolyzed until the starting compound has completely oxidized, a partial stream of the reaction solution is separated off and worked up. This partial stream is generally less than 5% by weight, preferably 0.01 to 1% by weight, of the total stream. Part of the gas dissolved in the reaction solution is discharged from the electrolysis circuit through this partial flow. A separate degassing of the entire reaction solution is not necessary, but can be advantageous in the case of small partial flows and relatively large amounts of gas. The partial flow is worked up as described above. Solvents, auxiliary electrolyte, starting compounds and, if appropriate, incompletely oxidized intermediates can be added to the reaction solution which is returned to the electrolytic cell. The recycled reaction solution is further replaced by the amount of starting compounds which corresponds to the amount of the separated product. After recycling and oxidation, the cycle described is repeated as often as required.

In all described embodiments, the reaction is carried out in the presence of an auxiliary electrolyte. This is generally in a concentration of 0.1 to 6% by weight, based on the reaction mixture. Protonic acids such as organic acids, e.g. Methylsulfonic acid, benzenesulfonic acid or toluenesulfonic acid, but also mineral acids such as sulfuric acid and phosphoric acid. Neutral salts can also be used as auxiliary electrolytes. Metal cations of lithium, sodium, potassium, but also tetraalkylammonium compounds such as tetramethylammonium, tetraethylammonium, tetrabutylammonium and dibutyldimethylammonium are suitable as cations. The following are to be mentioned as anions: fluoride, tetrafluoroborate, sulfonates such as methyl sulfonate, benzenesulfonate, toluenesulfonate, sulfates such as sulfate, methyl sulfate, ethyl sulfate, phosphates such as methyl phosphate, ethyl phosphate, dimethyl phosphate, diphenyl phosphate, hexafluorophosphate and phosphonyl methylphosphate, phosphonyl methylphosphate such as phosphonate methyl phosphonate.

Unbranched C ₁ -C ₆ -alkanols are preferably used as alkanols; methanol and ethanol are particularly preferred. The concentration of the alkanol in the feed to the electrolysis cell is generally 50 to 98% by weight, preferably 70 to 95% by weight.

The reaction mixture can contain one or more additional inert solvents. Compounds such as methylene chloride, acetonitrile, methyl tert-butyl ether, butyrolactone or dimethyl carbonate are suitable for this. The concentration of these solvents can be 0 to 30% by weight, based on the reaction mixture.

The current density in the process according to the invention is generally 2 to 10 A / dm ² , preferably 3 to 8 A / dm ² .

The total amount of charge transferred to the starting compound II in the process according to the invention is generally 3 to 9 F / mol II, preferably 4 to 8 F / mol II.

Precious metals such as platinum and oxides such as chromium or ruthenium oxide and mixed oxides such as Ti / RuO _x are suitable as anode materials. However, graphite is the preferred anode material.

Steel, iron, copper, zinc, nickel and coal as well as noble metals such as platinum are generally suitable as cathode materials; however, graphite is preferred.

The electrochemical oxidations can be carried out in divided, but preferably in undivided, flow cells. The oxidation is generally carried out at temperatures from 0 to 120 ° C., preferably at 20 to 80 ° C.

Process products I can be hydrolyzed to the corresponding aldehydes in a manner known per se. The compounds I thus represent storage-stable depot compounds for the much more sensitive aldehydes. The process according to the invention allows the starting compounds II to be converted into the products I with high conversion. Remarkably, the electrochemical oxidations proceed with high selectivity under these conditions. The by-products possibly formed in the reaction can be returned to the reaction without any special work-up steps. No interfering side reactions from such by-products were found.

Examples example 1 Electrosynthesis of p-tert-butylbenzaldehyde dimethyl acetal

All examples were carried out in an undivided flow cell with graphite electrodes at a distance of 1 mm from below. The reaction temperature was 55 ° C. The reaction pressure was generated by a pump. In the examples according to the invention the reaction solution was depressurized to normal pressure after oxidation. The gases released in the process were able to escape both in a discontinuous and continuous mode of operation. The current density in all examples was 3.4 A / dm ² , the amount of charge 7.5 F / mol of starting compound. The electrolyte was pumped around at 200 l / h.

450 g (15 Gew.-%)

p-tert.-Butyltoluol

10 g (0,3 Gew.-%)

Schwefelsäure

2450 g (84,7 Gew.-%)

Methanol

The electrolyte had the following composition:

450 g (15% by weight)

p-tert-butyltoluene

10 g (0.3% by weight)

sulfuric acid

2450 g (84.7% by weight)

Methanol

For working up, the electrolyte was neutralized with sodium methylate, the methanol was distilled off and the precipitated salt was filtered off. The stated products were obtained after vacuum distillation.

Example 1.1 According to the invention, discontinuously

Overpressure:

0.55 bar

Number of cycles:

700

1 %

p-tert.-Butyltoluol

3 %

p-tert.-Butylbenzylmethylether

78 %

p-tert.-Butylbenzaldehydimethylacetal

The following were isolated (data in mol%, based on the TBT used):

1 %

p-tert-butyltoluene

3%

p-tert-butylbenzyl methyl ether

78%

p-tert-butylbenzaldehyde dimethyl acetal

Example 1.2 According to the invention, continuously

Overpressure:

0.55 bar

Refurbished partial stream:

0.1% by weight of the total current

Inlet quantity:

220 g electrolyte / h

7 %

p-tert.-Butyltoluol

9 %

p-tert.-Butylbenzylmethylether

72 %

p-tert.-Butylbenzaldehyddimethylacetal

The following were isolated (data in mol%, based on the TBT used):

7%

p-tert-butyltoluene

9%

p-tert-butylbenzyl methyl ether

72%

p-tert-butylbenzaldehyde dimethyl acetal

Example 1.3 Comparison, discontinuous

Carried out as in Example 1.1, but without excess pressure in the electrolysis cell

1 %

p-tert.-Butyltoluol

18 %

p-tert.-Butylbenzylmethylether

61 %

p-tert.-Butylbenzaldehyddimethylacetal

The following were isolated (data in mol%, based on the TBT used):

1 %

p-tert-butyltoluene

18%

p-tert-butylbenzyl methyl ether

61%

p-tert-butylbenzaldehyde dimethyl acetal

Example 1.4 Comparison, continuous

Aufgearbeiteter Teilstrom:

0,1 Gew.-% des Gesamtstroms

Zulaufmenge:

220 g Elektrolyt/h

Carried out as in example 1.2, but without excess pressure in the electrolysis cell

Refurbished partial stream:

0.1% by weight of the total current

Inlet quantity:

220 g electrolyte / h

11 %

p-tert.-Butyltoluol

10 %

p-tert.-Butylbenzylmethylether

60 %

p-tert.-Butylbenzaldehyddimethylacetal

The following were isolated (data in mol%, based on the TBT used):

11%

p-tert-butyltoluene

10%

p-tert-butylbenzyl methyl ether

60%

p-tert-butylbenzaldehyde dimethyl acetal

erf. =

erfindungsgemäß

disk. =

diskontinuierlich

kont. =

kontinuierlich

TBT =

p-tert.-Butyltoluol

TBE =

p-tert.-Butylbenzylmethylether (Zwischenverbindung, die zum Acetal umgesetzt werden kann)

The following table shows the turnovers and selectivities for examples 1.1 to 1.4: example Turnover related to TBT + TBE Selectivity for acetal 1.1 erf. disk. 96% 81% 1.2 erf. cont. 84% 86% 1.3 comparison disk. 81% 76% 1.4 comparison cont. 79% 76%

req. =

according to the invention

disk. =

discontinuous

cont. =

continuously

TBT =

p-tert-butyltoluene

TBE =

p-tert-butylbenzyl methyl ether (intermediate compound which can be converted into the acetal)

These values clearly show that the embodiments according to the invention are superior both in terms of conversion and in terms of selectivity to the comparative examples in which the reaction mixture obtained after the electrooxidation was not relaxed to a pressure which is lower than that in the electrolysis cell .

Example 2 Electrosynthesis of p-tert-butylbenzaldehyde dimethyl acetal

A different auxiliary electrolyte was used than in Example 1.

450 g

(15 Gew.-%) p-tert.-Butyltoluol

10 g

(1 Gew.-%) Natriumbenzolsulfonat

2510 g

(84 Gew.-%) Methanol

The electrolyte had the following composition:

450 g

(15% by weight) p-tert-butyltoluene

10 g

(1% by weight) sodium benzene sulfonate

2510 g

(84 wt%) methanol

The electrooxidation was carried out in a cell as described in Example 1 at 55 ° C. The current density was 3.4 A / dm ² . The different charge quantities can be found in the following table. The procedure was analogous to Example 1. For working up, the reaction solution was freed from methanol by distillation, the salt which precipitated was filtered off and the acetal was purified by distillation. The electrolyte was pumped around at 200 l / h.

Example 2.1 According to the invention, discontinuously

Overpressure:

0.55 bar

Number of cycles:

700

0,2 %

p-tert.-Butyltoluol

2 %

p-tert.-Butylbenzylmethylether

83 %

p-tert.-Butylbenzaldehyddimethylacetal

The following were isolated (data in mol%, based on the TBT used):

0.2%

p-tert-butyltoluene

2%

p-tert-butylbenzyl methyl ether

83%

p-tert-butylbenzaldehyde dimethyl acetal

Example 2.2 According to the invention, continuously

Refurbished partial stream:

0.15% by weight of the total current

Inlet quantity:

307 g electrolyte / h

9 %

p-tert.-Butyltoluol

12 %

p-tert.-Butylbenzylmethylether

72 %

p-tert.-Butylaldehyddimethylacetal

The following were isolated (data in mol%, based on the TBT used):

9%

p-tert-butyltoluene

12%

p-tert-butylbenzyl methyl ether

72%

p-tert-butylaldehyde dimethyl acetal

Example 2.3 Comparison, discontinuous

Carried out as in Example 2.1, but without excess pressure in the electrolysis cell

1 %

p-tert.-Butyltoluol

12 %

p-tert.-Butylbenzylmethylether

64 %

p-tert.-Butylaldehyddimethylacetal

Beispiel Ladungsmenge F/mol TBT Umsatz bzgl. TBT+TBE Selektivität bzgl. Acetal 2.1 erf. disk. 7,5 98 85 2.2 erf. kont. 6,0 79 91 2.3 Vergleich disk. 7,5 87 74 The following were isolated (data in mol%, based on the TBT used):

1 %

p-tert-butyltoluene

12%

p-tert-butylbenzyl methyl ether

64%

p-tert-butylaldehyde dimethyl acetal

example Amount of charge F / mol TBT Turnover related to TBT + TBE Selectivity for acetal 2.1 erf. disk. 7.5 98 85 2.2 req. cont. 6.0 79 91 2.3 comparison disk. 7.5 87 74

The examples show that, in a batchwise procedure under otherwise identical conditions, both conversion and selectivity in the process according to the invention are significantly higher than in the comparative example. Furthermore, the selectivity can be further increased with a high volume of charge by continuous operation with a small amount of charge transferred.

Example 3

Electrosynthesis of p-tolylaldehyde dimethyl acetal (discontinuous)

Apparatus:

as in example 1

Temperature:

70 ° C

Current density:

3.4 A / dm ²

Amount of charge:

5.5 F / mol

Overpressure:

0.55 bar

Number of cycles:

750

450 g

(15 Gew.-%) Xylol

30 g

(1 Gew.-%) Kaliumbenzolsulfonat

2540 g

(84 Gew.-%) Methanol

The electrolyte had the following composition:

450 g

(15% by weight) xylene

30 g

(1% by weight) potassium benzene sulfonate

2540 g

(84 wt%) methanol

4 %

p-Methylbenzylmethylether

81 %

p-Tolylaldehyddimethylacetal

After carrying out and working up in analogy to Example 1.1, the following were isolated:

4%

p-methylbenzyl methyl ether

81%

p-tolylaldehyde dimethyl acetal

The conversion, based on the starting compound and p-methylbenzyl methyl ether, was 96% and the selectivity (with respect to acetal) was 84%.

Example 4

Apparatur:

wie in Beispiel 1

Temperatur:

50°C

Stromdichte:

4,2 A/dm²

Ladungsmenge:

4,5 F/mol

Überdruck:

0,35 bar

Electrosynthesis of p-anisaldehyde dimethyl acetal (continuous, with recycling of isolated compounds)

Apparatus:

as in example 1

Temperature:

50 ° C

Current density:

4.2 A / dm ²

Amount of charge:

4.5 F / mol

Overpressure:

0.35 bar

15 Gew.-%

p-Methoxytoluol

0,4 Gew.-%

Natriumbenzolsulfonat

83,1 Gew.-%

Methanol

3,5 Gew.-%

Rückführungsstrom

Durchführung und Aufarbeitung wie in Beispiel 1.3The electrolyte had the following composition:

15% by weight

p-methoxytoluene

0.4% by weight

Sodium benzenesulfonate

83.1% by weight

Methanol

3.5% by weight

Return current

Execution and processing as in Example 1.3

The recycle stream contained the components which boiled more easily than the product when the substream was worked up by distillation.

The conversion, based on the starting compound and p-methoxybenzyl methyl ether, was 78% and the selectivity (with regard to acetal) was 91%.

Claims (4)

1. A process for the preparation of a benzaldehyde dialkyl acetal of the formula I

   

   where R¹ is C₁-C₆-alkyl, R² is C₁-C₆-alkyl, C₁-C₆-alkoxy, halogen, cyano or carboxyalkyl where the alkyl group is of 1 to 6 carbon atoms, n is an integer of from 1 to 3 and the radicals R² may be identical or different when n is > 1, by electrochemical oxidation of a substituted toluene compound of the formula II

   

   wherein a substituted toluene compound II is oxidized in the presence of an alkanol R¹-OH and of an auxiliary electrolyte in an electrolysis cell, the reaction solution thus obtained is let down outside the electrolysis cell to a pressure which is from 10 mbar to 10 bar lower than the pressure in the electrolysis cell and

   A) in the batchwise procedure, the gas released from the reaction solution on letting down the latter is separated off and the reaction solution is recycled at least once to the electrolysis cell, subjected to electrolysis, let down, separated from the released gas and then worked up to obtain the product, or

   B) in the continuous procedure, some of the reaction solution is worked up to obtain the product and the remaining part of the reaction solution is mixed with an amount of the originally used reaction solution which corresponds to the part removed and is recycled to the electrolysis cell, subjected to electrolysis and let down.
2. A process as claimed in claim 1, wherein a substituted toluene compound of the formula III

   

   where R³ is C₁-C₆-alkyl or C₁-C₄-alkoxy, is converted.
3. A process as claimed in claim 1 or 2, wherein the reaction solution is let down to atmospheric pressure.
4. A process as claimed in claim 1 or 2, wherein the reaction solution is let down to a pressure which is from 0.1 to 6 bar lower than the pressure in the electrolysis cell.