JPS6023659B2 - Method for producing hydroxy monomandelic acid compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing hydroxy monomandelic acid compounds.

A method for producing a hydroxymandelic acid compound by reacting a phenol compound and glyoxylic acid in a basic aqueous solution is known (see Japanese Patent Publication No. 37-4122).

According to this method, the reaction rate of the starting phenol compound was low, and the yield of the hydroxy monomandelic acid compound based on the consumed phenol compound was also low. Therefore, this method was not necessarily advantageous as an industrial method for producing hydroxy monomandelic acid compounds. The present invention provides a method for producing hydroxy monomandelic acid compounds in high yield.

That is, this invention is based on the general formula or (where RI represents a hydroxyl group and a lower alkoxy group, and R2 represents a lower alkyl group).

) and glyoxylic acid in a basic aqueous medium in the presence of 0.001 ta or more of cyclodextrin and/or starch per night of the phenol compound, and at a temperature in the range of 0 to 50 qo. The present invention relates to a method for producing a hydroxy monomandelic acid compound characterized by the following. Next, the method of this invention will be explained. The phenol compound is represented by the following general formula.

(However, RI and R2 in the formula have the same meanings as above.) Specific examples of phenolic compounds include catechol, resorcinol, hydroquinone, 2-methoxyphenol, 3-methoxyphenol, 4-methoxyphenol, 2-ethoxyphenol 3-ethoxyphenol,
4-ethoxyphenol, 2-n-propoxyphenol, 3-n-propoxyphenol, 4mn-propoxyphenol, 2-iso-propoxyphenol, 3
-iso-propoxyphenol, 4-iso-propoxyphenol, 4-methylphenol, 4-ethylphenol, 4-n-propylphenol and 4-ls
Examples include o-propylphenol.

Glyoxylic acid may be used as is, or in the form of its alkali salts, such as sodium glyoxylate,
It may also be used as potassium glyoxylate.

There are no particular restrictions on the amount of glyoxylic acid used, but
The amount is usually 0.5 to 2 mol, preferably 0.5 to 1.0 mol per mol of the phenol compound.

In the method of this invention, cyclodextrin and/or starch are used as catalysts. Examples of cyclodextrins include Q-type cyclodextrin, B-type cyclodextrin, and Y-type cyclodextrin. A particularly preferred cyclodextrin is type B cyclodextrin. As the starch, a known starch having an amylose content of 20 to 25% can be used, and specifically, potato starch, wheat starch, sweet potato starch, corn starch, etc. can be used. The amount of cyclodextrin and/or starch used is 0.00 per phenolic compound.
1? The above value is preferably 0.01 ta or more.

If the amount of cyclodextrin and/or starch used is less than the above-mentioned lower limit, the yield of the hydroxy monomandelic acid compound will decrease. There is no particular restriction on the upper limit of the amount of catalyst used, but even if it is used in an excessively large amount, the yield of the hydroxy monomandelic acid compound will not become higher, and it will take more time to remove cyclodextrin and/or starch after the reaction. Therefore, the amount of catalyst used per phenol compound is usually 1.0 or less. The reaction is carried out using basic water in which a basic compound such as sodium hydroxide, potassium hydroxide, or sodium carbonate is dissolved as a medium.

The reaction does not substantially proceed in a neutral or acidic aqueous medium. There is no particular restriction on the amount of water used, but usually 200 to 1000 of water is used per mole of phenol compound. The reaction temperature is 0 to 50 pm, preferably 10 to 50 pm.
She is 40 years old.

If the reaction temperature is lower than 0.000000, the reaction rate will be low, which is undesirable, and if the reaction temperature is higher than 50.000, glyoxylic acid will change to oxalic acid and glycolic acid by the Cannillo reaction, which is not preferred. The reaction time varies somewhat depending on the type of phenol compound used as a raw material, but is usually between 12 and 2 hours.

The hydroxy monomandelic acid compound obtained by the method of the present invention has the general formula: Any one of Y in each formula is CH(OH)-COO.

]. Specific examples of hydroxy monomandelic acid compounds include 3,4-dihydroxymandelic acid, 2,4
monodihydroxymandelic acid, 2,6-dihydroxymandelic acid, 2,5-dihydroxymandelic acid, 4-hydroxy-3-methoxymandelic acid, 2-hydroxy-3-methoxymandelic acid, 2-hydroxy-4-methoxymandelic acid, 2-hydroxy-6-methoxy mandelic acid,
4-hydroxy-2-methoxymandelic acid, 2-hydroxy-5-methoxymandelic acid, 3-ethoxy-4-hydroxymandelic acid, 3-ethoxy-2-hydroxymandelic acid, 4-ethoxy-2-hydroxymandelic acid,
6-ethoxy-2-hydroxymandelic acid, 2-ethoxy-4-hydroxymandelic acid, 5-ethoxy-2-hydroxymandelic acid, 4-hydroxy-3-n-propoxymandelic acid, 2-hydroxy-3-n-propoxymandelic acid, 2-hydroxymandelic acid 4-n-propoxymandelic acid, 2-hydroxy-6-n-propoxymandelic acid, 4-hydroxy-2-n-propoxymasoderic acid,
2-hydroxy-5-n-propoxymandelic acid, 4-hydroxy-3-iso-propoxymandelic acid, 2-hydroxy-3-iso-propoxymandelic acid, 2-
Hydroxy-4-iso-propoxymandelic acid, 2-
Hydroxy-6-lso-propoxymandelic acid, 4-
Hydroxy-2-iso-propoxymandelic acid, 2-hydroxy-5-iso-propoxymandelic acid, 2-hydroxy-5-methoxymandelic acid, 5-ethoxy-2
-Hydroxy-5-methoxymandelic acid, 5-ethoxy-2-hydroxymandelic acid, 2-hydroxy-5-n
-propylmandelic acid and 2-hydroxy-5-is
Examples include o-propylmandelic acid. The hydroxy monomandelic acid compound obtained by the method of the present invention is very useful as a synthetic raw material for various pharmaceuticals or as an intermediate for perfume preparations.

According to the method of the present invention, a hydroxy monomandelic acid compound can be obtained in high yield, and the by-product of a hydroxydimandelic acid compound can be suppressed. Next, examples and comparative examples will be shown.

In addition, the hydroxymandelic acid compound was quantitatively determined by converting the hydroxymandelic acid compound obtained by the reaction into a formylated phenol compound according to a known method of oxidizing in a basic aqueous solution, and measuring this by gas chromatography. Examples 1 to 5 50 mmol of a phenolic compound of the type listed in the first category, 14.25 mmol of a 2% aqueous solution by weight of glyoxylic acid, and 3.0 mmol of 8-cyclodextrin were added to 85 mmol of a 1N aqueous sodium hydroxide solution. The mixture was added and dried at 25 qo for 24 hours.

After the reaction is complete, add la standard hydrochloric acid to the reaction solution to
Set the H value to 6, then set it to 3 for each 100 areas of Jethyl Ether.
Unreacted phenol compounds were recovered by multiple extractions to obtain a yuzu residue aqueous solution containing a hydroxymandelic acid compound.

Furthermore, in order to determine the yield of the hydroxymandelic acid compound, the above-mentioned raffinate aqueous solution was charged into an autoclave together with 1N sodium hydroxide aqueous solution 100% and oxidized steel (0) powder 0.6%, and the pressure was 2k9/s. Hydroxybenzaldehyde was obtained by reacting the solution with 125q0 for 1.5 hours under a vacuum while passing air through the aqueous solution at a flow rate of 0.15 cm/min (gauge pressure).

To the oxidation reaction mixture obtained by furnace-separating the oxidized steel (0) powder, 11% of la standard hydrochloric acid was added to adjust the pH value to 1.5.
Extracted three times.

The extract was analyzed by gas chromatography. The results are shown in Table 1.

Comparative Examples 1-5 Examples 1-5 except that 8-cyclodextrin was not used
The procedure was performed in the same manner as in 5.

The results are shown in Table 1.

Examples 6 to 8 A raffinate aqueous solution containing a hydroxymandelic acid compound was obtained by carrying out the same procedure as in Example 1, except that a divalent phenol compound of the type listed in the second description was used as the phenol.

Furthermore, in order to determine the yield of hydroxymandel oxide, the above yuzu residue aqueous solution was mixed with a 2N sodium bicarbonate aqueous solution
It was charged into an autoclave along with 23 g of oxidized steel powder and 23 g of oxidized steel (0) powder, and heated under 125 ml of oxidized steel powder while flowing nitrogen gas into the aqueous solution at a pressure of 2 k9/m (gauge pressure) and a flow rate of 0.2 m/min. 1 at °C. Hydroxybenzaldehyde was obtained by an hourly reaction.

The oxidation reaction mixture obtained by furnace-separating the oxidized steel (D) powder was adjusted to a pH value of 2 by adding 45 liters of LA standard hydrochloric acid, and the oxidation reaction mixture was extracted five times with 200 units of diethyl ether each. The extract was analyzed by gas chromatography. The results are shown in Table 2.

Comparative Examples 6-8 Example 6 except that 8-cyclodextrin was not added
The procedure was performed in the same manner as in steps 8 to 8.

The results are shown in Table 2.

Table 2 Examples 9 to 12 The same procedure as Example 1 was carried out except that the types of phenolic compounds and catalysts listed in Table 3 were used.

The results are shown in Table 3.

Example 13 The same procedure as Example 6 was carried out except that starch was used instead of 3-cyclodextrin.

The results are shown in Table 3. Table 3

Claims (1)

[Claims] 1 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ or ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (However, R^1 in the formula represents a hydroxyl group and a lower alkoxy group, and R^ 2 represents a lower alkyl group) and glyoxylic acid in a basic aqueous medium, and cyclodextrin and/or starch at a concentration of 0.001 g per 1 g of the phenol compound.
A method for producing a hydroxy monomandelic acid compound, characterized in that the reaction is carried out at a temperature in the range of 0 to 50°C.