JPS6029372B2 - 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 with glyoxylic acid is described in PB Report No. 92190
It is known from Tsubaki Kosho No. 37-4122.

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

The method described in Japanese Patent Publication No. 37-4122 uses Cu
, Fe, Co, Mn, Ni, Pt, Ag, Mountain, Cr, V
A 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 was a drawback that a long reaction time of 4 to 8 hours was required to obtain a hydroxybenzaldehyde compound with a yield of 80 to 85%.

Moreover, since the above-mentioned catalyst also has the effect of promoting the decomposition and alteration of the produced hydroxybenzaldehyde compound, when the reaction time is further extended, the yield of the hydroxybenzaldehyde compound tends to decrease rather than the above-mentioned yield. The inventors have arrived at this invention as a result of intensive research into a method for producing hydroxybenzaldehyde compounds in a short reaction time and in high yield.

That is, the present invention relates to the production of a hydroxybenzaldehyde compound, which is characterized in that a hydroxymandelic acid compound is oxidized with a molecular oxygen-containing gas in a basic aqueous medium without a catalyst in a reaction vessel made of stainless steel. It is about law.

The material of the reaction vessel used in the method of this invention is stainless steel, for example, SUS301 according to the JIS standard, SUS
302, SUS304, SUS309, S
US310, SUS316, SUS321,
SUS347, SUS403, SUS405, S
US41 stop SUS420, SUS430, SUS43
Examples include stainless steels designated by the symbols SUH330 and SUH330.

When using a stainless steel reaction vessel as described above,
The oxidation reaction is carried out satisfactorily even in the absence of any conventionally known catalyst, and once the hydroxybenzaldehyde compound is produced, there is no decomposition or deterioration of the hydroxybenzaldehyde compound. The hydroxymandelic acid compound used in the method of this invention is represented by formula (1).

(RI represents either a hydrogen atom, a lower alkyl group, a lower alkoxy group, or 10H(OH)COO, and at least one of the three RIs is -OH(OH)C
It's OO day.

Further, R2 represents any one of a hydrogen atom, a lower alkyl group, and a lower alkoxy group. ) Specific examples of hydroxymandelic acid compounds include 2-hydroxymandelic acid, 4-hydroxymandelic acid, 4-hydroxy-2-methylmandelic acid, 4-hydroxy-3-methylmandelic acid, 2-hydroxymandelic acid,
-Hydroxy-3-methylmandelic acid, 2-hydroxy-4-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-hydroxymandelic 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-hydroxy-5-n-propylmandelic acid, 2-hydroxy-3-n-propylmandelic acid,
-Hydroxy-6-n-propylmandelic acid, 2-te
n-butyl-4-hydroxymandelic acid, 3-butyl-4-hydroxymandelic acid, 3-butyl-2-hydroxymandelic acid, 4-te-butyl-2-
Hydroxymandelic acid, 5-te-butyl-2-hydroxymandelic acid, 6-n-butyl-2-hydroxymandelic acid, 2,3-di-rt-butyl-4-hydroxymandelic acid, 2,5-di-hydroxymandelic acid "t-butyl-4-hydroxymandelic acid, 3,5-di-te-91 butyl-4
-Hydroxymandelic acid, 3,4-di-butyl-2-hydroxymandelic acid, 3,6-dirt-butyl-2-hydroxymandelic acid, 4,5-diter
t-butyl-2-hydroxymandelic acid, 4,6-di-rt-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-hydroxy-3-n-propoxymasoderic acid, 2-hydroxy-4-n-propoxymandelic acid, 2-hydroxy -5-n-propoxymandelic acid, 2-hydroxy-6-n-propoxymandelic acid, 2
-te-butoxy-4-hydroxymandelic acid, 3-te-butoxy-hydroxymandelic acid, 3-ten
-Butoxy-2-hydroxymandelic acid, 4-te-
Butoxy-2-hydroxymandelic acid, 5-tert-butoxy-2-hydroxymandelic acid, 6-rt-butoxy-2-hydroxymandelic acid, 2,3-di-te
rt-butoxy 4-hydroxymandelic acid, 2,5-di-tert-butoxy 4-hydroxymandelic acid,
3,5-di-butoxy-4-hydroxymandelic acid, 3,4-di-butoxy-2-hydroxymandelic acid, 3,6-di-butoxy-2-hydroxymandelic acid, 4,5-di-te-9-butoxy-2- Hydroxymandelic acid, 4.6G and rt-butyl-2-
Examples include hydroxymandelic acid.

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 10-3% muscle volume. When the oxygen concentration is less than 5% by volume, the oxidation reaction rate decreases and a long reaction time is required, and when the oxygen concentration is more than 5% by volume, some decomposition or alteration of the hydroxybenzaldehyde compound occurs. Undesirable. There are no particular restrictions on the oxidation temperature, but it is usually 80 to 150°C, preferably 100 to 125°C.

The oxidation reaction may be carried out under normal pressure or under increased pressure. There is no particular restriction on the oxidation reaction time, but the reaction is usually completed in 15 to 2 minutes.

The hydroxybenzaldehyde compound obtained by the method of this invention is represented by formula (D).

(R2 represents the same meaning as above, R3 represents any one of a hydrogen atom, a lower alkyl group, a lower alkoxy group, and one CHO, and at least one R3 among the three R3s is -CHO.) Hydroxy Specific examples of benzaldehyde 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-hydroxy-21n-propylbenzaldehyde, 4-hydroxy-31n-propylbenzaldehyde, 2-hydroxy-31n-propylbenzaldehyde, 2-hydroxy-41n-bropylbenzaldehyde, 2-hydroxy-51n-propyl Benzaldehyde, 2-hydroxy-6-propylbenzaldehyde, 2-te-butyl-4-hydroxybenzaldehyde, 3-ten-butyl-4-hydroxybenzaldehyde, 3-ten-butyl-2-hydroxybenzaldehyde, 4-rt-butyl-2-hydroxybenzaldehyde , 5 rt-butyl-2-hydroxybenzaldehyde, 6-te-butyl-2-hydroxybenzaldehyde, 2,3-di-ten-butyl-4
-Hydroxybenzaldehyde, 2,5-di-tert
-butyl-4-hydroxybenzaldehyde, 3,5-
di-rt-butyl-4-hydroxybenzaldehyde, 3,4-di-ten-butyl-2-hydroxybenzaldehyde, 3,6-di-te-butyl-2-hydroxybenzaldehyde, 4,5-di-butyl-2
-Hydroxybenzaldehyde, 4,6-dirt-butyl-2-hydroxybenzaldehyde, 4-hydroxy-2-methoxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, 2-hydro-3
-Methoxybenzaldehyde, 2-hydroxy-4-methoxybenzaldehyde, 2-hydroxy-5-methoxybenzaldehyde, 2-hydroxy-6-methoxybenzaldehyde, 2-ethoxy4-hydroxybenzaldehyde, 3-ethoxy4-hydroxybenzaldehyde, 3-ethoxy2-hydroxybenzaldehyde, 4-ethoxy2- hydroxybenzaldehyde,
5-Ethoxy-2-hydroxybenzaldehyde, 6-ethoxy-2-hydroxybenzaldehyde, 4-hydroxy-21n-propoxybenzaldehyde, 4-hydroxy-31n-propoxybenzaldehyde, 2-
Hydroxy-3-n-propoxybenzaldehyde, 2
-Hydroxy-4-n-propoxybenzaldehyde,
2-Hydroxy-5-n-propoxybenzaldehyde, 2-hydroxy-6-n-propoxybenzaldehyde, 2-ten-butoxybenzaldehyde, 3-nir
t-butoxy 4-hydroxybenzaldehyde, 3-ten-butoxy 2-hydroxybenzaldehyde,
4 rt-butoxy-2-hydroxybenzaldehyde, 51te 91ptoxy-2-hydroxybenzaldehyde, 61te-butoxy-2-hydroxybenzaldehyde, 2,3-di rt-butoxy-4-hydroxybenzaldehyde, 2.5 -di-ten-butoxy-4-hydroxybenzaldehyde, 3,5-di-t
ert-butoxy 4-hydroxybenzaldehyde,
3,4-di-butoxy-2-hydroxybenzaldehyde, 3,6-di-ten-poxy-2-hydroxybenzaldehyde, 4,5-di-rt-butoxy-2-hydroxybenzaldehyde, 4,6-di-t
Examples include en-butyl-2-hydroxybenzaldehyde.

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, or xylene. Extract.

Then, the hydroxybenzaldehyde compound is isolated by distilling this organic solvent layer. According to the method of this invention, the reaction time, which previously required 4 to 8 hours, can be reduced to 20 hours.
The yield can reach 95% or more since the hydroxybenzaldehyde compound produced does not undergo decomposition or deterioration under the oxidation reaction conditions.

Examples 1 to 14 A solution of 100 mol of hydroxymandelic acid compound dissolved in 300 mol of 1.5N caustic soda aqueous solution was placed in various stainless steel reaction vessels, and 1.0 mol of hydroxymandelic acid compound was dissolved in 300 mol of 1.5N caustic soda aqueous solution. Air was supplied at a flow rate of 10,000 yen, and an oxidation reaction was carried out for 2 minutes at 10,000 yen while stirring.

After cooling the reaction product liquid, 40 parts of a 12N aqueous hydrochloric acid solution was added to bring the pH of the reaction product liquid to about 2, and from this strongly acidic reaction product liquid, jethyl ether was added with 400 parts each of Z.
An extract was obtained by extraction twice.

This extract was analyzed by gas chromatography. Table 1 shows the hydroxybenzaldehyde compound obtained at that time and its yield. Table 1 Comparative Examples 1 to 5 The same procedure as in Example 1 was carried out except that a glass reaction vessel was used and metal powder was used as a catalyst.

Table 2 shows the hydroxybenzaldehyde compound and its yield over time. Table 2 Reference Examples 1 to 3 100 mmol of hydroxybenzaldehyde compound,
In a glass reaction vessel, 300 liters of 1.9 N caustic soda solution was dissolved on the table, and 500 ml of metal oxide powder was added to this aqueous solution, and then air was introduced into the aqueous solution at a flow rate of 1.0 min. The residual rate of the hydroxybenzaldehyde compound was measured every hour while keeping the temperature at 100°C.

The results are shown in Table 3. Reference example 4 In a reaction vessel made of stainless steel (SUS316), 4-
Hydroxy-3-methoxybenzaldehyde 100 m
OL was dissolved in 300 g of a 1.9N caustic soda aqueous solution, and air was added into this aqueous solution at a flow rate of 1.0 m/min. -The residual rate of hydroxy-3-methoxybenzaldehyde was measured.

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 without a catalyst in a stainless steel reaction vessel.