JPS6029373B2 - Method for producing hydroxybenzaldehyde compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing hydroxybenzaldehyde compounds useful as raw materials for pharmaceuticals and fragrances in a short period of time and in high yield.

The production of hydroxybenzaldehyde by oxidizing hydroxymandelic acid obtained by adding phenol or 2-alkoxyphenol and glyoxylic acid is described in PB Report No. 92190 and Japanese Patent Publication No. 37-4122.

PB report no. The method described in 92190 involves heating and oxidizing hydroxymandelic acid in a basic aqueous medium using cupric oxide as an oxidizing agent under normal pressure or pressure. Since the amount is extremely large (5 to 7 times), a large amount of solid matter must be filtered through a furnace, and in order to reuse the obtained oxidized No. 1 steel, there is a drawback that an oxidation process of cuprous oxide is required.

The method described in Japanese Patent Publication No. 37-4122 uses Cu, F
e, Co, Mn, Ni, Pt, Ag, AI, Cr, V,
Hydroxymandelic acid compound is oxidized with a molecular oxygen-containing gas in a basic aqueous medium using a powder such as Hg, oxide, chloride, sulfate, etc. as a catalyst.
There is a drawback that a reaction time of 4 to 8 hours is required to obtain a hydroxybenzaldehyde compound with a yield of 0 to 85%.

Moreover, since the catalyst described above has the effect of promoting decomposition and alteration of the hydroxybenzaldehyde compound, even if the reaction time is further extended, the hydroxybenzaldehyde compound cannot be obtained in a higher yield than the above-mentioned yield. The inventors have arrived at this invention as a result of intensive studies on a method for producing hydroxybenzaldehyde compounds in a short reaction time and in high yield. That is, the present invention relates to a method for producing a hydroxybenzaldehyde compound, which is characterized by oxidizing a hydroxymandelic acid compound with a molecular oxygen-containing gas in a basic aqueous medium in the presence of yellow steel and/or bronze.

Specific examples of yellow steel and bronze used in the method of this invention include Shichisan brass, Admiralty brass, Naval brass,
Examples include aluminum yellow steel, German silver, silicon bronze, and nickel bronze.

There are no particular restrictions on the form of use of the yellow steel and/or bronze used in the method of this invention, including lumps, plates, granules,
It may be in powder form.

Further, the surface of the inner wall of the reaction vessel that comes into contact with the reaction liquid may be made of yellow steel and/or bronze. When using yellow steel and/or bronze in granular or powder form, the diameter of the particles is 0.01
~0.1 skin is desirable.

Further, when used in the form of granules or powder, the amount of yellow steel and/or bronze to be used is preferably 0.5 to 200 units, particularly preferably 10 to 100 units per mole of the hydroxymandelic acid compound. When yellow steel and/or bronze is used in the form of a lump or plate, its surface area is particularly preferably from 20 to 150,000, particularly preferably from 100 to 50,000 per mole of the hydroxymandelic acid compound.

The hydroxymandelic acid compound used in the method of this invention is represented by formula (1).

[RI represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, or one CH(OH)COO, and at least one of the three RIs is -CH(OH)C
It's OO day.

Further, R2 represents a hydrogen atom, a lower alkyl group, or a lower alkoxy group. ] Examples of odorants of hydroxymandelic acid compounds include 2-hydroxymandelic acid, 4-hydroxymandelic acid, 4-hydroxy-2-methylmandelic acid, 4-hydroxy-3-methylmandelic acid, 2-hydroxy-3-methylmandelic acid, and 2-hydroxy-4-methylmandelic acid.
-Methylmandelic acid, 2-hydroxy-5-methylmandelic acid, 2-hydroxy-6-methylmandelic acid, 2-ethyl-4-hydroxymandelic acid, 3-ethyl-4-
Hydroxymandelic acid, 3-ethyl-2-hydroxymandelic acid, 4-ethyl-2-hydroxymandelic acid, 5
-ethyl-2-hydroxymandelic acid, 6-ethyl-2
-Hide.

Ximandelic acid, 4-hydroxy-2-n-propylmandelic acid, 4-hydroxy-3-n-propylmandelic acid, 2-hydroxy-3-n-propylmandelic acid, 2
-Hydroxy-4-n-propylmandelic acid, 2-hydro. xy-51n-propylmandelic acid, 2-hydroxy-61n-propylmandelic acid, 21ten-butyl-
4-hydroxymandelic acid, 3-te-butyl-4-hydroxymandelic acid, 3-te-butyl-2-hydroxymandelic acid, 4-ten-butyl-2-hydroxymandelic acid, 5-[e-butyl-2- Hydroxymandelic acid, 6-tert-butyl-2-hydroxymandelic acid, 2,3-di-tert-butyl-4-hydroxymandelic acid, 2,5-di-rt-butyl-4-hydroxymandelic acid, 3,5-di-tert-butyl-4-hydroxymandelic acid, butyl-4-hydroxymandelic acid, 3,4-di-ten-butyl-2
-Hydroxymandelic acid, 3,6-di-rt-butyl-2-hydride. ximanderic acid, 4,5-di-tert-
Butyl-2-hydroxymandelic acid, 4,6-di-r
t-Butyl-2-hydroxymandelic acid, 4-hydroxy-2-methoxymandelic acid, 4-hydroxy-3-methoxymandelic acid, 2-hydroxy-3-methoxymandelic acid, 2-hydroxy-4-methoxymandelic acid, 2
-Hydroxy-5-methoxymandelic acid, 2-hydroxy-6-methoxymandelic acid, 2-ethoxy-4-hydroxymandelic acid, 3-ethoxy-4-hydroxymandelic acid, 3-ethoxy-2-hydroxymandelic acid, 4
-ethoxy-2-hydroxymandelic acid, 5-ethoxy-2-hydroxymandelic acid, 6-ethoxy-2-hydroxymandelic acid, 4-hydroxy-2-n-propoxymandelic acid, 4-hydroxy-3-n-propoxymandelic acid, 2-hydro. xy-3-n-propoxymandelic acid, 2-hydroxy-4-n-propoxymandelic acid, 2-hydroxy-5-n-propoxymandelic acid, 2-hydroxy-5-n-propoxymandelic acid,
-Hydroxy-6-n-propoxymandelic acid, 2-t
e-butoxy 4-hydroxymandelic acid, 3-te
Lebutoxy-4-hydroxymandelic acid, 3-ter
t-butoxy-2-hydroxymandelic acid, 4-rt
-butoxy 2-hydroxymandelic acid, 5-rt-
Butoxy-2-hydroxymandelic acid, 6-te-butoxy-2-hydroxymandelic acid, 2,3-di-te
n-butoxy-4-hydroxymandelic acid, 2,5-di-rt-butoxy-4-hydroxymandelic acid, 3.
5-di rt-butoxy-4-hydroxymandelic acid, 3,4-di rt-butoxy-2-hydroxymandelic acid, 3,6-di-te t-butoxy-2-hydroxymandelic acid, 4. 5-G tert-Butoxy 2
-hydroxymandelic acid, 4,6-di-ten-butoxy-2-hydroxymandelic acid, and the like. The basic aqueous medium is an aqueous solution in which a basic substance such as sodium hydroxide, potassium hydroxide, or sodium carbonate is dissolved.

The amount of this basic substance to be used is preferably 2 to 6 times the mole of the hydroxymandelic acid compound. Examples of the molecular oxygen-containing gas include air and a mixed gas in which pure oxygen is diluted with an inert gas such as nitrogen or argon.

The oxygen concentration in molecular oxygen-containing gas is usually 5 to 5% by volume.
, particularly preferably 10 to 3% by volume. When the oxygen concentration is less than 5% by volume, the oxidation reaction rate is low and a long reaction time is required, and when the oxygen concentration is greater than 5% by volume of the feed, some decomposition or alteration of the hydroxybenzaldehyde compound occurs. So I don't like it. There are no particular restrictions on the oxidation temperature, but it is usually 80 to 150 qo, preferably 100 to 1250 qo.

The oxidation reaction may be performed under normal pressure or under increased pressure. There is no particular restriction on the oxidation reaction time, but the reaction usually ends in 15 to 20 minutes. The hydroxybenzaldehyde compound obtained by the method of this invention is (b)
It is expressed by the formula.

[R2 represents the same meaning as above, R3 is a hydrogen atom,
Represents either a lower alkyl group, a lower alkoxy group or -CHO, and at least one R3 among the three R3
is -CHO. ] Specific examples of hydroxybenzaldehyde compounds include 2-hydroxybenzaldehyde,
4-hydroxybenzaldehyde, 4-hydroxy-2
-Methylbenzaldehyde, 4-hydroxy-3-methylbenzaldehyde, 2-hydroxy-3-methylbenzaldehyde, 2-hydroxy-4-methylbenzaldehyde, 2-hydroxy-5-methylbenzaldehyde, 2-hydroxy-6-methylbenzaldehyde, 2-
Ethyl-4-hydroxybenzaldehyde, 3-ethyl-4-hydroxybenzaldehyde, 3-ethyl-2-
Hydroxybenzaldehyde, 4-ethyl-2-hydroxybenzaldehyde, 5-ethyl-2-hydroxybenzaldehyde, 6-ethyl-2-hydroxybenzaldehyde, 4-hydro-2-n-propylbenzaldehyde, 4-hydroxy-3-n-propylbenzaldehyde , 2-hydroxy-3-n-propylbenzaldehyde, 2-hydroxy-4-n-propylbenzaldehyde, 2-hydroxy-5-n-propylbenzaldehyde, 2-hydroxy-6-n-propylbenzaldehyde, 2-te-butyl-4-hydroxy Benzaldehyde, 3 rt-butyl-4-hydroxybenzaldehyde, 3 9-butyl-2-hydroxybenzaldehyde, 4 rt-butyl-2-hydroxybenzaldehyde, 5 rt-butyl-2-hydroxybenzaldehyde, 6 te Butyl-2-hydro.

xybenzaldehyde, 2,3-di-ten-butyl-4-hydroxybenzaldehyde, 2,5-di-ter
t-butyl-4-hydroxybenzaldehyde, 3.5
-di-rt-butyl-4-hydoxybenzaldehyde, 3,4-di-ten-butyl-2-hydroxybenzaldehyde, 3,6-di-mten-butyl-2-hydroxybenzaldehyde, 4,5-di-rt-butyl-2 -Hydroxybenzaldehyde, 4,6-di-r
t-Butyl-2-hydroxybenzaldehyde, 4-hydroxy-2-methoxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydroxy-3-methoxybenzaldehyde, 2-hydroxy-4
-Methoxybenzaldehyde, 2-hydroxy-5-methoxybenzaldehyde, 2-hydroxy-6-methoxybenzaldehyde, 2-ethoxy-4-hydroxybenzaldehyde, 3-ethoxy4-hydroxybenzaldehyde, 3-ethoxy-2-hydroxybenzaldehyde, 4-ethoxy-2-hydroxybenzaldehyde, 5 -ethoxy 2-hydroxybenzaldehyde,
6-ethoxy-2-hydroxybenzaldehyde, 4-hydroxy-2-n-propoxybenzaldehyde, 4
-Hydroxy-3-n-propoxybenzaldehyde,
2-Hydroxy-3-n-propoxybenzaldehyde, 2-hydroxy-4-n-propoxybenzaldehyde, 2-hydroxy-5-n-propoxybenzaldehyde, 2-hydroxy-6-n-propoxybenzaldehyde, 2-te-butoxybenzaldehyde, 3-hydroxy rt-butoxy 4-hydroxybenzaldehyde,
3-te-butoxy-2-hydroxybenzaldehyde, 4-te-butoxy-2-hydroxybenzaldehyde, 5-te-butoxy-2-hydroxybenzaldehyde, 6-te-butoxy-2-hydroxybenzaldehyde, 2,3-di-butoxybenzaldehyde. rt-butoxy-4-hydroxybenzaldehyde, 2,5-di-butoxy-4-hydroxybenzaldehyde, 3,5-di-t
ert-butoxy 4-hydroxybenzaldehyde,
3,4-di-rebutoxy-2-hydro. xybenzaldehyde, 3,6-di-te-butoxy-2-hydroxybenzaldehyde, 4,5-di-te-butoxy-2-hydroxybenzaldehyde, 4,6-di-te-n
-Butoxy 2-hydride. Examples include xybenzaldehyde. The hydroxybenzaldehyde compound can be isolated from the oxidation reaction mixture, for example, by the following method. A key acid such as hydrochloric acid or sulfuric acid is added to the oxidation reaction mixture until its pH value becomes 7 or less, preferably 5 or less, and the hydroxybenzaldehyde compound is extracted from the reaction mixture with an organic solvent such as ether, benzene, toluene/xylene, etc. Extract.

Then, the hydroxybenzaldehyde compound is isolated by distilling this organic solvent layer. According to the method of the present invention, the conventional reaction time of 4 to 8 hours can be shortened to about 2 minutes, and the hydroxybenzaldehyde compound produced does not undergo decomposition or deterioration under oxidation reaction conditions, so its yield can be reduced. The rate reaches over 95%.

Next, examples, comparative examples, and reference examples will be shown.

Examples 1 to 14 In a glass reaction vessel, the average particle size was 0.
1.5 to dissolve 100 mmol of hydroxymandelic acid compound in the presence of various yellow steel or bronze crystals of 0.06 ribs.
Air was supplied into the specified caustic soda aqueous solution at a flow rate of 1.0 min, and an oxidation reaction was carried out at 10,000 ℃ for 20 minutes while shaking.

After cooling the reaction product solution, 40% of aqueous hydrochloric acid solution calculated as LA was added to adjust the pH to about 2, and the strongly acidic reaction product solution was extracted three times with 400% of diethyl ether each to obtain an extract.

This extract was analyzed by gas chromatography. The obtained hydroxybenzaldehyde compound and its yield are shown in Table 1. Table 1 Example 15 Instead of powdered yellow steel, 71 Yanagi (length), 246 Yanagi (width), thickness 1
The process was carried out in the same manner as in the previous example except that the side plate-shaped nickel bronze was used.

4-Hydroxy-3-methoxybenzaldehyde 14.
73 ml was produced, and the yield was 96.8%.

Comparative Example The same procedure as in Examples 1 to 14 was carried out, except that instead of Alloys 1 to 7, the powders shown in Table 2 having an average particle size of 0.06 mm were used.

Table 2 shows the hydroxybenzaldehyde compound and its yield over time. Table 2 Reference Examples 1 to 9 In a glass reaction vessel, 100 mmol of a hydroxybenzaldehyde compound was dissolved in 300 μm of a 1.5N aqueous solution of caustic soda, and a powder of willow metal oxide with an average particle size of 0.06 was added to this aqueous solution. After adding powder of willow alloy with an average particle size of 0.06 or without adding anything to this aqueous solution, air was supplied into this aqueous solution at a flow rate of 1.0 m/min. Table 3 shows the change over time in the residual rate of the hydroxybenzaldehyde compound at each time while maintaining the temperature at 100 oo.

Claims (1)

[Claims] 1. A method for producing a hydroxybenzaldehyde compound, which comprises oxidizing a hydroxymandelic acid compound with a molecular oxygen-containing gas in a basic aqueous medium in the presence of brass and/or bronze.