CS277365B6 - A process for the preparation of 3-alkoxy-4-hydroxyhene-aldehydes - Google Patents

Abstract

A method for the production of 3-alkoxy-4-hydroxybenzaldehydes, the essence of which is the reaction of 2-alkoxyphenol with glyoxylic acid in the presence of an alkali hydroxide, after which the resulting reaction mixture is oxidized with oxygen in the presence of a copper complex.

Description

The invention relates to a new process for the preparation of 3-alkoxy-4-hydroxybenzaldehydes from 2-alkoxyphenol and glyoxylic acid.

3-Alkoxy-4-hydroxybenzaldehydes are usually prepared by reacting 2-alkoxyphenols with formaldehyde to give 3-alkoxy-2-hydroxybenzyl alcohol, which is oxidized with 3-nitrosobenzenesulfonic acid, which is prepared in situ in a reaction mixture from nitrobenzenesulfonic acid and granular or powdered aluminum. However, this process produces a large amount of waste water which contains methanilic acid and therefore the reaction of 2-alkoxyphenol with glyoxylic acid has recently been used instead of 3-alkoxy-4-hydroxymandelic acid, which is then subsequently oxidized. to 3-alkoxy-4-hydroxybenzoylcarboxylic acid and subsequent decarboxylation affords the desired 3-alkoxy-4-hydroxybenzaldehyde.

However, the latter approach has so far had a number of disadvantages. It was assumed that the condensation had to be carried out at a low temperature (about 18 ° C) and that it was therefore necessary to cool the reaction mixture. The device therefore required powerful cooling units. Next, after the reaction, the mixture was acidified, and unreacted 2-alkoxyphenol was extracted, followed by the addition of sodium hydroxide to the reaction mixture, followed by oxidation. Substituted mandelic acid was originally oxidized with copper oxide. After oxidation, it was necessary to laboriously remove the copper oxide formed by filtration (British Intelligence Objective Sub-committee, Final Report 1726). This procedure has been further improved and its more efficient variants and modifications are described in a number of patents. Belgian Patent No. 877,911 and U.S. Patent 2,640,083 use copper compounds in an acidic environment, Japanese Patent 412,262 discloses oxidation with cobalt chloride in alcohol, or describes the use of metallic copper or copper oxide in the presence of oxygen (Japanese Patent 7,924,842.77 966 693), copper alloys can also be used. It is also possible to use the electrochemical oxidation process (USSR Pat. No. 55,799, Japanese Pat. No. 7,729,739). The above-described use of copper oxide is followed by a catalytic process using activated copper and copper oxide (CS AO 265 937). The disadvantage of these methods is that the surface of the catalyst, whether suspended or anchored, is inactivated by the deposition of resins and minerals causing water hardness. Its catalytic efficiency gradually decreases and oxidation yields fluctuate.

The above problems are solved by a process for the preparation of 3-alkoxy-4-hydroxybenzaldehydes having an alkyl group of 1 to 4 carbon atoms, the essence of which is that 1 mole of 2-alkoxyphenol is reacted with 0.6 to 1.4 moles of glyoxylic acid and 0 , 6 to 2.6 moles of sodium and / or potassium hydroxide at a temperature of 20 to 60 ° C for 0.2 to 24 hours, after which the resulting reaction mixture is oxidized with oxygen with 0.002 to 0.2 moles of copper in the form of a complex at a temperature of 40 up to 100 ° C.

The advantage of the process according to the invention is that it provides a high yield of the desired 3-alkoxy-4-hydroxybenzaldehyde and a relatively simple technological device is sufficient for its implementation. The main advantage is that in the production process according to the invention, the waste water contains only sodium sulphate and slight traces of copper and organic substances. It is also possible to significantly reduce the total amount of waste products compared to the old production method.

If the starting 2-alkoxyphenol contains dialkoxybenzene formed in the preparation of 2-alkoxyphenol, it can be extracted with an organic solvent, for example diethyl ether or toluene, before oxidation. Ethylenediamine, diethylenetriamine, nitrilotriacetic acid, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, or some other substances can be used as complexing agents. Part of the alkali hydroxide can be replaced by alkali carbonate or caustic hydroxide. After completion of the reaction, 3-alkoxy-4-hydroxybenzaldehyde is isolated in a conventional manner, i.e., extraction into an organic solvent, followed by purification by distillation and crystallization.

3-alkoxy-4-hydroxybenzaldehydes having 1 to 2 carbon atoms (vanillin and bourbonal) are used as fragrances, higher derivatives are used as starting materials in drug synthesis.

The production method according to the invention is further elucidated in the following examples, which, however, do not limit the scope of the invention in any way.

Exemplary embodiments

Example 1

2500 l of water are introduced into a stirred, heated reactor, to which 1 kmol of sodium hydroxide and 1.1 kmol of 2-ethoxyphenol are added. After dissolving the 2-ethoxyphenol on the phenolate, 1 kmol of glyoxylic acid in the form of a 50% solution is metered in linearly at 40 DEG C. for 3 hours separately with 1 kmol of sodium hydroxide in the form of a 40% solution. The mixture is kept at 40 ° C after the raw materials have been added and stirred for a further 3 hours. The still hot is pumped to an oxidation reactor equipped with heating, a circulating pump with a venturi or another type of liquid-gas mixing system. To the mixture were added 0.1 km of sodium hydroxide and 800 ml of a catalyst solution prepared as follows: 0.32 mol of sodium hydroxide and 0.08 mol of ethylenediaminetetraacetic acid were dissolved in 400 ml of distilled water, and 0.08 mol of copper sulfate after dissolving it. After dissolving the copper sulphate, the catalyst solution is made up to 800 ml with distilled water.

After the addition of the catalyst solution, the mixture is pumped through a circulation pump through a venturi or other mixing system for 6 hours while heating to 80 ° C. The progress of the reaction is monitored by determining the degree of conversion of 3-ethoxy-4-hydroxymandelic acid to 3-ethoxy-4-hydroxybenzoylcarboxylic acid by capillary isotachophoresis methods.

After completion of the reaction, 3-ethoxy-4-hydroxybenzoylcarboxylic acid is decomposed in the presence of toluene with dilute sulfuric acid in a flow-through stirred decarboxylation reactor or in a static mixer to 3-ethoxy-4-hydroxybenzaldehyde and carbon dioxide. The liberated 3-ethoxy-4-hydroxybenzaldehyde is then extracted with toluene in a countercurrent extractor. A toluene solution containing 130 kg of 3-ethoxy-4-hydroxybenzaldehyde (80% of theory per glyoxylic acid charged) is further processed according to a generally known method.

Example 2

As in Example 1, 1.2 kmol of 2-methoxyphenol are reacted in an alkaline medium with 1 kmol of glyoxylic acid in a flow reactor with a residence time at 55-60 ° C for 30 minutes. The oxidation is carried out as in Example 1, instead of the Cu complex with ethylenediaminetetraacetic acid, the Cu complex with diethylenetriaminepentaacetic acid (4.10 .mu.mol of Cu per 2500 liters of charge) is used. The obtained 3-methoxy-4-hydroxybenzaldehyde contains practically no isomers.

Claims (1)

Process for the preparation of 3- = alkoxy-4-hydroxybenzaldehydes from 2-alkoxyphenol, characterized in that 1 mol of 2-alkoxyphenol is reacted with 0.6 to 1.4 mol of glyoxylic acid and 0.6 to 2.6 mol of sodium hydroxide and / or potassium at a temperature of 20 to 60 ° C for 0.2 to 24 hours, after which the resulting reaction mixture is oxidized with oxygen with 0.002 to 0.2 moles of copper in the form of a complex at a temperature of 40 to 100 ° C.