NO137891B - PROCEDURES FOR THE PREPARATION OF AROMATIC HYDROXYALDEHIDS - Google Patents

Description

The invention relates to a process for the production of aromatic hydroxyaldehydes, which contain hydroxy groups: in the aromatic residue in the 2-, 3- or 4-position and optionally substituted with further hydroxy groups as well as with C-^-Cg-alkyl groups, halogen or C-^ -C 6 alkyl residues.

US patent no. 2,062,205 discloses a method for the production of aromatic hydroxyaldehydes by simultaneous oxidation and decarboxylation of hydroxyaryl, glycolic acids in an alkaline medium. The method according to the invention differs from this method in that the hydroxyarylglycolic acids are reacted not in an alkaline medium, but in an acidic medium,

;if the pH value is below 5 with oxidizing agents. In the method according to the invention, the aromatic hydroxyaldehydes are obtained in a significantly simpler way during significantly shorter reaction times and in improved yields than according to the methods that work in alkaline media, since large amounts of metal hydroxide are produced during the oxidation in alkaline media - southern mud which reduces the reaction rate and makes the Sopp processing of the reaction mixture so difficult that it. no more is feasible technically practical.

A further disadvantage of the known methods is that when working in an alkaline environment and the acidification required at the end of the reaction, at least 2 mol of salt are formed per

moles of hydroxyaldehyde, which burdens the wastewater as waste. The finding that the oxidation of the hydroxyarylglycolic acids can also be carried out in acidic media was therefore surprising, because it is known that the free hydroxyarylglycolic acids, as they exist in the acidic media, are unstable. The known instability of the free hydroxyarylglycolic acids is the reason why the oxidation has so far only been carried out in alkaline media, i.e. in media in which the acids exist in the form of their stable salts.

The invention thus relates to a method for the production of aromatic hydroxyaldehydes which contain hydroxy groups in the aromatic residue in the 2-, 3- or I-position and are optionally substituted with further hydroxy groups as well as with G-L-Cg alkoxy groups, halogen or C 1-Cg alkyl residues by simultaneous oxidation of decarboxylation of hydroxyarylglycolic acids which contain the hydroxy group in the aromatic residue in the 2-, 3- or 4-position and optionally substituted with further hydroxy groups as well as with C-^-Cg alkoxy groups, halogen or C^-Cg-alkyl residues, in that the method is characterized by reacting hydroxyarylglycolic acids in an aqueous medium with oxidizing agents at a pH value lower than 5"

The aromatic glycolic acids used in the method according to the invention may contain the hydroxy group in the aromatic residue in the 2-, 3- or 4-position. Furthermore, they can also contain several hydroxy groups and additional substituents,

like for example. alkoxy groups, halogens, preferably chlorine or bromine or alkyl radicals, which preferably have up to 6 carbon atoms. Examples of such compounds are the following: 4-hydroxy-phenylglycolic acid, 4-hydroxy-3-methoxy-phenylglycolic acid, 4-hydroxy-3-ethoxy-phenylglycolic acid, 4-hydroxy-2-methoxy-phenylglycolic acid, 4-hydroxy-3, 5-dimethoxy-phenylglycolic acid, 4-hydroxy-2-chloro-phenylglycolic acid, 4-hydroxy-3-chloro-phenylglycolic acid, 4-hydroxy-3,5-dichloro-phenylglycolic acid, 4-hydroxy-3-bromo-phenylglycolic acid 4-hy hydroxy-3-methyl-phenylglycolic acid, 4-hydroxy-3,5-dimethylphenylglycolic acid, 4-hydroxy-3,5-diethyl-phenylglycolic acid 4-hydroxy-3j 5-di-tert.-butyl-phenylglycolic acid, 3-hydroxy- phenylglycolic acid, 3-hydroxy-4-methoxy-phenyl-glycolic acid, 3-hydroxy-4-chloro-phenylglycolic acid, 3-hydroxy-4-methyl-phenylglycolic acid, 2-hydroxy-phenylglycolic acid, 2-hydroxy-4-methoxy- phenylglycolic acid, 2-hydroxy-4-methyl-phenylglycolic acid, 3,4-dihydroxy-phenylglycolic acid, 4-hydroxy-2,3-benzo-phenyl-glycolic acid or 2-hydroxy-5,6-benzo-phenylglycolic acid or α-naphthylglycolic acid.

Particularly preferred starting materials for use in the method according to the invention are 4-hydroxy-phenylglycolic acid, 4-hydroxy-3-methoxy-phenylglycolic acid, 4-hydroxy-3-ethoxy-phenylglycolic acid.

The aforementioned compounds can, for example, be obtained by

glycolic acid is reacted with the corresponding pheno'1.

It is not absolutely necessary to use the aromatic glycolic acids in their pure state from the reaction, but the aromatic glycolic acids can also be used as they appear during the preparation for the method according to the invention.

Exemplary representatives of oxidizing agents

in the mentioned area are reducible metal salts such as e.g. copper (II) salts, mercury (II) salts, iron (III) salts, nickel (III) salts, cobalt (III) salts, chromium (VI) salts, lead (IV) salts, iridium-(IV) salts and palladium-(II) salts. as well as alkali halides such as alkali chlorates, alkali bromates, alkali iodates or alkali nitrates.

Copper (II) salts, mercury (II) salts, iron (III) salts, nickel (III) salts, cobalt (III) salts or alkali chlorates are preferably used.

Particularly preferred are copper (II) sulfate, copper (II) chloride, mercury (II) acetate, iron (III) chloride, iron (III) sulfate, nickel (III) phosphate , cobalt (III) chloride, potassium chlorate or sodium chlorate.

An oxidizing agent is used for reaction with the hydroxyarylglycolic acids in the method according to the invention.

in equivalent amounts or in excess, e.g. 4 equivalents, preferably equivalent quantities or in excess up to 2 equivalents.

Of course, the mentioned reducible metal salts can

can also be used in the desired mixture. It has proven particularly suitable to use potassium chlorate or sodium chlorate in mixture with iron, cobalt, nickel sulphate or chloride.

The reducible metal salts can of course also be produced during the reaction in situ in a redox system, for example by using a mixture of sodium chlorate and iron sulphate.

Particularly preferred for the method according to the invention are oxidizing agents, which have redox potentials in the range of EQ = +0.17 volts up to EQ = +1.84 volts.

In a particular embodiment of the method according to the invention, the reaction takes place in an aqueous, acidic solution, catalytically using oxygen as an oxidizing agent. Palladium or platinum is preferably used as a catalyst.

In a further special embodiment of the method according to the invention, instead of the chemical oxidizing agent mentioned for the specified potential range, of course the reaction also takes place in an aqueous, acidic solution by anodic oxidation.

The method according to the invention is carried out in an acidic medium, preferably at pH values of 0 - 5, particularly preferred at pH values of 0.3 - 3. Usually a special acid addition is superfluous as the hydroxyarylglycolic acids used in an aqueous medium have a sufficient intrinsic acidity, and furthermore, during the oxidation, in many cases, a sufficient amount of acid is released, e.g. hydrochloric or sulfuric acid. If necessary, however, the pH value can be adjusted by adding the corresponding amount of a mineral acid, for example semi-concentrated sulfuric acid.

The water-soluble hydroxyaromatic glycolic acids can be oxidized by these oxidizing agents in acidic, homogeneous aqueous solution at room temperature or elevated temperature, e.g. up to 150°C, preferably 50 to 100°C during rapid and practically quantitative decomposition of CO2 into the corresponding aromatic hydroxyaldehydes.

Acid- and oxidation-sensitive aldehydes, such as vanillin and ethyl vanillin, can be dissolved in the presence of water-immiscible solvents, of which the corresponding glycolic acids are hardly absorbed, e.g. benzene and toluene, remove the acidic oxidation solution and isolate from the extract in the usual way.

The acidic oxidation solution can be regenerated electrochemically or by oxidation with atmospheric oxygen or with other suitable oxidizing agents.

Surprisingly, despite the way of working in an acidic medium, no condensation products appear.

The compounds according to the invention can, for example, find use as flavoring and odorants.

The general applicability of the present method for the production of aromatic hydroxyaldehydes is illustrated by the following examples:

Example 1.

10 g of 4-hydroxy-3-methoxy-phenylglycolic acid (molecular weight 198) is dissolved in 100 g of water and mixed at 75 - 80°C during 20 to 30 minutes with 82 g of an aqueous 20% FeCl-j solution as a lively CC^ development starts which ends after a further 30 minutes and as the reaction takes place at a pH value between 2 and 0.8. From the acidic oxidation solution, the main amount of the formed 4-hydroxy-3-methoxybenzaldehyde completely crystallizes out on cooling. With benzene or toluene, 14-hydroxy-3-methoxy-benzaldehydes can be completely extracted from the oxidation solution. The extract is washed with a little water, then the solvent is distilled off to such an extent that 4-hydroxy-3-methoxy-benzaldehyde can be combined with cyclohexane or light petrol in crystalline form from the mother liquor.

Yield: 7.2 g of 4-hydroxy-3-methoxybenzaldehyde

= 95% of the theoretical.

Analysis: Melting point 79 to 80°C, according to CO number and thin-layer chromatogram pure 4-hydroxy-3-methoxybenzaldehyde (the CO number appears from a measuring analytical aldehyde test;

state according to the oxymation method). Example 2. 10 g of 4-hydroxy-3-methoxy-phenylglycolic acid are dissolved in 100 g of water and mixed at 100°C during 30 minutes with 86 g of an aqueous 20% solution of CuC^ • 2 F^O as a moderate CC^ development takes place which ends after a further 2 hours at 100 C and the reaction takes place at a pH value of 1.8 - 0.8. The preparation of the acidic oxidation solution takes place as indicated in example 1.

Yield: 6.8 g of 4-hydroxy-3-methoxybenzaldehyde

= 89$ of the theoretical.

Analysis: Melting point 78 to 79°C, pure according to CO number and thin layer chromatogram. Example 3.

Oxidation of the crude condensation product of Guajacol + glycol-. acid.

a) An acidic aqueous solution of 4-hydroxy-3-methoxy-phenylglycolic acid which was formed according to example 3b is heated

with 2000 ml of toluene until reflux temperature 85 to 86°C

and mixed with stirring with 800 g of iron (II) sulphate portionwise over the course of 1 hour, with lively CO 2 evolution taking place and the reaction taking place at a pH value of 2 - 0.8. The toluene solution is separated and the mixture is stirred with fresh toluene

a further hour at 85°C and the two phases separate again. The mixture is then stirred for a third hour without toluene at 100°C until final CO 2 evolution and then extracted completely with toluene. Processing of the toluene extracts takes place as in example 1. Yield: 265 g of 4-hydroxy-3-methoxybenzaldehyde = 86% of the theoretical amount (calculated on converted guaiacol according to example 3b).

Analysis: Melting point 77 to 78°C, degree of purity according to CO number

and thin layer chromatogram 97%.

b) Preparation of the material used: 356 g of 50% aqueous glyoxylic acid (2.4 mol) is neutralized at 15 to

25°C with 1920 g of 5% caustic soda, then mixed with a solution of 372 g of guaiacol (3 mol) in 1200 g of 10% caustic soda with stirring and allowed to stand for 36 hours at 15 to 25°C. The alkaline condensation mixture is then acidified with 50% sulfuric acid while cooling to pH 4 to 5. From the acidic solution, 124.5 g of unreacted guaiacol is extracted with toluene. Example 4.

9.3 g of 4-hydroxy-phenylglycolic acid as monohydrate (molecular weight 186) is heated in 50 g of water and mixed first at 75' to 80°C during 20 to 30 minutes with 82 g of an aqueous 20% FeCl -j solution as a lively C02 evolution starts which is finished after a further 30 minutes at 100°C and as the reaction takes place at a pH value of 2 - 0.8. The main amount of the formed 4-hydroxybenzaldehyde crystallizes from the acidic oxidation solution on cooling to 0°C and is sucked off. Residual 4-hydroxybenzaldehyde is removed from the cold, aqueous mother liquor by repeated extraction with benzene. The main quantity of the p-hydroxy-benzaldehyde is added to the benzene solution thus formed, the benzene is strongly evaporated and pure 4-hydroxy-benzaldehyde is precipitated crystalline with light petrol or cyclohexane.

Yield: 5.2 g of 4-hydroxybenzaldehyde = 85% of the theoretical. Analysis: Melting point 115 to 116°C, without contamination according to

CO number 100% according to thin layer chromatogram.

Example 5-

Oxidation of the crude condensation product of phenol and glyoxylic acid.

a) An acidic, aqueous solution of 4-hydroxy-phenylglycol acids which was formed according to example 5b, is mixed at 75 to 80°C with stirring with 800 g of iron (III) sulfate in portions over the course of 1 hour, a lively CC^ evolution takes place which is finished at 100°C after a further hour and as the reaction takes place at a pH value of 2 - 0.8. From the acidic oxidation solution, p-hydroxybenzaldehyde is recovered as in example 4. Since the crude condensation product of phenol with glyoxylic acid next to 4-hydroxy-phenylglycolic acid also contains smaller amounts of 2-hydroxyphenylglycolic acid, a little salicylaldehyde is also produced during the oxidation, which after precipitation of the 4-hydroxybenzaldehyde, which in example 4 remains in the mother liquor.

Yield: 197 g of 4-hydroxybenzaldehyde = 81% of the theoretical.

17 g of a mixture of

20? 4-hydroxy-benzaldehyde and

Q0% salicylaldehyde = 7% of the theoretical amount

(calculated on converted phenol according to example 5b).

b) Preparation of the material used: 336 g of 53% aqueous glyoxylic acid (2.4 mol) is neutralized at 15 to

25°C with 1920 g of 5% caustic soda, then mix with a solution of 282 g of phenol (3 mol) in 1200 g of 10% caustic soda with stirring and leave for 36 hours at 15 to 25°C. the alkaline condensation mixture is made with 50% sulfuric acid while cooling to pH 4 to 5. From the acidic solution, 95 g of unreacted phenol is extracted with benzene.

Example 6.

11.5 g of 4-hydroxy-3-ethoxy-phenylglycolic acid as monohydrate (molecular weight 230) is dissolved in 100 ml of water. The acidic solution (pH 2) is overlaid with 100 ml of toluene and the mixture is heated to 75 to 80°C. While stirring, at this temperature, 56.7 g of a 30% FeCl₂ solution is added over the course of 20 minutes, as lively CC₂ evolution begins. The mixture is then boiled for a further 20 minutes under reflux (85 to 86°C). After separation of the toluene phase, the remaining aqueous solution is heated to boiling, the remaining amount of CC^ being developed in the course of 10 minutes. After oxidation, the oxidation solution is hydrochloric acid (pH 1) and is extracted completely with toluene. The combined toluene solutions are washed with a little water, then filtered and the solvent is distilled off to the extent that 4-hydroxy-3-ethoxy-benzalde can be precipitated from the mother liquor with cyclohexane or light petrol.

hyd in crystalline form.

Yield: 7.7 g = 93% of the theoretical.

Analysis: Melting point 75 to 76°C, according to CO number and thin layer chromatogram practically pure 4-hydroxy-3-ethoxy-benzaldehyde.

Example 7-

10 g of 4-hydroxy-3-methoxy-phenylglycolic acid (molecular weight 198) is dissolved in 100 g of water. The aqueous, acidic solution (pH 2) is overlaid with 100 ml of toluene and heated with stirring to 75 to 85°C. From 75°C, a solution of 0.5 g of FeCl-j in 1 g of water is first added, then a solution of 2.1 g of KCIO^ in 38 g of water is dosed over the course of 10 minutes, as a strong C02 is released -development, which ends at 85°C after 30 minutes. The oxidation solution has a pH value of approximately 1 after oxidation has been completed. After removal of the toluene extract, the aqueous oxidation solution is heated at 95 to 100°C until CO 2 evolution has ended after 20 to 30 minutes.

From the acidic oxidation solution, the main amount of the formed U-hydroxy-3-methoxy-benzaldehyde crystallizes out completely on cooling. With benzene or toluene, the 4-hydroxy-3-methoxybenzaldehyde can be completely extracted from the oxidation solution. The extract is washed with a little water, then the solvent is distilled off to the extent that it can be precipitated from the mother liquor in crystalline form 4-hydroxy-3-methoxybenzaldehyde with cyclohexane. Yield: 5j3 g of crystallized 4-hydroxy-3-methoxybenzaldehyde.

A further 1.4 g of 4-hydroxy-3-methoxybenzaldehyde is contained in 1.9 g of residue.

Total yield: 7.6 g = 87% of the theoretical.

Example 8.

a) .11j5 g of 4-hydroxy-3-ethoxy-phenylglycolic acid as monohydrate (molecular weight 230) is dissolved in 100 g of water. The watery,

acid solution (pH 2) is overlaid with 100 ml of toluene and heated with stirring at 75 - 85°C. From 75°C, a solution of 0.5 g of FeCl-j in 1 g of water is first added, then a solution of 1.82 g of NaClO^ in 35 g of water is dosed over the course of 10 minutes, as a lively C02 starts ~development, which terminates at 85°C after 35 minutes.

The oxidation solution has a pH value of approximately 1 after the oxidation has been completed. After removal of the toluene extract, the aqueous oxidation solution is heated at 95 - 100°C, until the evolution of C2 has ended, after 30 minutes.

The extraction of the oxidation solution with toluene and the processing of the extract takes place as in example 6. Yield: 7>4 g 4-hydroxy-3-ethoxy-benzaldehyde 90% of the

theoretical quantity.

Analysis: Melting point 75°C, according to measurement analysis and thin-layer chromatogram practically pure 4-hydroxy-3-ethoxy-benzaldehyde. b) A similar result is obtained if, instead of iron chloride, an equivalent amount of iron sulphate is used.

Example 9.

Oxidation of the crude condensation product of guaiacol + glyoxylic acid.

a) An aqueous, acidic solution of 4-hydroxy-3-methoxy-phenylglycolic acid, which was prepared according to example 9b, is brought

with 37.5 g of 50% sulfuric acid to a pH value of 0.8 to 0.9. 100 g of iron (II) sulfate solution and 372 g of 5% sodium chlorate solution in portions over the course of one hour, with lively CO 2 evolution taking place. The oxidation solution has a pH value of approximately 1 after oxidation is complete. The toluene solution is separated and the mixture is stirred with fresh toluene for a further hour at 85°C and the two phases are separated again. The mixture is then stirred for a third hour without toluene at 100°C until final C02 evolution and then extracted completely with toluene. The processing of the toluene extract takes place as in example 1 .

Yield: 47.5 g of 4-hydroxy-3-methoxyphenylglycolic acid = 95% of the theoretical amount (calculated on converted guaiacol according to

example 9b).

Analysis: Melting point 77 to 78°C, degree of purity according to CO number

and thin-layer chromatogram approx. 95%.

b) Preparation of the material used: 50 g of 50% aqueous glyoxylic acid (0.34 mol) is neutralized at 15 to

25°C with 225 g of 7% caustic soda, then mixed with a solution of 63 g of guaiacol (0.46 mol) in 319 g of 7% caustic soda under

stirring and leave for 36 hours at 15 to 25°C. The alkaline condensation mixture is then brought to a pH value of approx. 75 g of 60% sulfuric acid. 3- From the acidic solution, 21 g of unreacted guaiacol are extracted with toluene.

c) Corresponding results are obtained when iron (II) sulphate solution is used as an oxidizing agent instead

a cobalt (II) sulfate solution or a nickel (II) sulfate solution.

Comparative examples■

Experiment 1. (Similar to previous example 2).

10 g of 4-hydroxy-3-methoxy-phenylglycolic acid, prepared from glycolic acid and guaiacol corresponding to example 4 (US patent no. 2,062,205) was dissolved in 100 ml of water and at 100°C

during 30 minutes mixed with 86 ml of an aqueous 20% solution of CuC^ . 2 P^O. After a further 2 hours of stirring at 100°C, it was cooled and the clear reaction mixture was extracted several times with benzene. The combined organic phases were washed with a little water and the solvent removed.

Yield: 6.9 g (90% of theoretical) vanillin. Experiment 2. (Corresponding to example 4 in US patent no. 2,062,205).

10 g of 4-hydroxy-3-methoxy-phenylglycolic acid was adjusted to pH 8 with caustic soda (15%) and mixed with 25 g

copper (II) sulphate and 70 ml caustic soda (15%). The reaction mixture was heated for 2 hours at 100°C, then the formed copper sludge was filtered off. After cooling, the filtrate was acidified and extracted several times with benzene. The combined organic phases were washed with a little water and the solvent removed.

Yield: 4 g (52% of theoretical) vanillin.

By using CuC^ as oxidizing agent instead of CuSOjj, the same yield was obtained.

Claims (3)

1. Process for the preparation of aromatic hydroxyaldehydes which contain hydroxy groups in the aromatic residue in the 2-, 3- or 4-position and are optionally substituted with further hydroxy groups as well as with O^-Cg alkoxy groups, halogen or C-^-Cg alkyl residues by simultaneous oxidation and decarboxylation of hydroxyarylglycolic acids which contain the hydroxy group in the aromatic residue in the 2-, 3- or 4-position and which are optionally substituted with further hydroxy groups as well as with C-^-Cg alkoxy groups of halogen or C-^Cg-alkyl residues , characterized by reacting the hydroxyarylglycolic acids in an aqueous medium with the oxidizing agent at a pH value lower than 5. 2. Method according to claim 1, characterized in that one works in a pH range from 0.3 to 3- 3. Method according to claims 1-2, characterized in that potassium chlorate or sodium chlorate is used in a mixture with iron, cobalt, nickel sulphate or chloride.