JPS5822136B2 - Method for producing 3-hydroxy-4-methoxybenzaldehyde compound - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing a 3-hydroxy-4-methoxybenzaldehyde compound by selectively monomethylating the hydroxyl group at the 4-position of the 3,4-dihydroxybenzaldehyde compound.

3-Hydroxy-4-methoxybenzaldehyde compounds are useful as intermediates for pharmaceuticals, agricultural chemicals, etc.
-Hydroxy-4,5-dimethoxybenzaldehyde is hydrogen-reduced to obtain 3-hydroxy-4,5-dimethoxytoluene, which is then oxidized to 2,3-dimethoxy-5-methyl-1,4- It is known that benzoquinone can be obtained and is useful as a raw material for the synthesis of coenzyme Q homologs, which have recently attracted attention in biochemistry.

Conventionally, 3-hydroxy-4-methoxybenzaldehyde compounds, particularly 3-hydroxy-4,5-dimethoxybenzaldehyde, have been prepared using 3,4-dihydroxy-5-methoxybenzaldehyde, equimolar potassium hydroxide aqueous solution and equimolar dimethyl sulfate. However, in addition to the desired product, large amounts of 3.4.5-1-dimethoxybenzaldehyde and syringaldehyde are produced as by-products (J, Amer, Cnem, Soc,
, 74.4262 (1952)], so it was not advantageous.

The present inventors conducted various studies on the conditions under which the hydroxyl group at the 4-position of a 3,4-dihydroxybenzaldehyde compound is selectively monomethylated, and as a result, they arrived at the present invention.

That is, the present invention provides dimethyl sulfuric acid in an amount of 1 to 1.2 mol per mol of a 3,4-dihydroxybenzaldehyde compound represented by the general formula; 3-hydroxy-, represented by the general formula; The present invention relates to a method for producing a 4-methoxybenzaldehyde compound.

The general formula used in the method of the present invention is represented by 3
, 3 as a 4-dihydroxybenzaldehyde compound
, 4-dihydroxybenzaldehyde, 3,4-dihydroxy-5-methoxybenzaldehyde, 3,4-dihydroxy-5-ethoxybenzaldehyde, 3,4-dihydroxy-5-propoxybenzaldehyde, and the like.

The proportion of dimethyl sulfuric acid used in the method of the present invention is preferably 1 to 1.2 moles per mole of the 3,4-dihydroxybenzaldehyde compound.

If more than this amount is used, both the 3- and 4-position hydroxyl groups of the 3,4-dihydroxybenzaldehyde compound will be methylated, or the 3-position hydroxyl group will be methylated, which is not preferable.

Further, the alkaline agent used in the method of the present invention is sodium carbonate, and it is usually preferable to use it in an amount equal to or more than the same mole relative to the dimethyl sulfate used.

The reaction of the present invention is carried out in an aprotic polar solvent such as acetone, dimethyl sulfoxide, dioxane, etc.
Side reactions occur in aqueous solutions.

The reaction temperature is suitably in the range of room temperature to 151°C, and is usually preferably around the reflux temperature of the solvent.

As the 3-hydroxy-4-methoxybenzaldehyde compound represented by the general formula (II) obtained by the method of the present invention, 3-hydroxy-4-methoxybenzaldehyde, 3-hydroxy-4,5-dimethoxybenzaldehyde, 3-hydroxy -4-methoxy-5-ethoxybenzaldehyde, 3-hydroxy-4-methoxy-5-propoxybenzaldehyde and the like.

As described above, by implementing the method of the present invention, 3.4-
A 3-hydroxy-4-methoxybenzaldehyde compound in which the hydroxyl group at the 4-position of the dihydroxybenzaldehyde compound is selectively monomethylated can be obtained.

Example 1 3.4-dihydroxy-5-methoxybenzaldehyde 7,69 (45 mmol), dimethyl sulfate 6.7 g (
53 mmol) and sodium carbonate 6, Oi (57
mmol)2 in 80 Ttl of acetone for 4 hours.
The reaction was carried out at reflux temperature.

After the reaction was completed, the P solution from which the product had been separated was concentrated, dissolved in aqueous sodium hydroxide solution, and this solution was washed with toluene.
4.5-Trimethoxybenzaldehyde was removed.

The aqueous solution was then neutralized with salt:acid, extracted with ether, and the extract was distilled under reduced pressure to obtain 6.9.9% of 3-hydroxy-4,5-dimethoxybenzaldehyde (yield: 841%).

The melting point was 61°C.

The yield of 3,4.5-trimethoxybenzaldehyde was 10%, and the yield of syringaldehyde was 3%.

Example 2 A reaction was carried out at 100'C for 2 hours in the same manner as in Example 1 except that the solvent was changed from acetone to dimethyl sulfoxide.

The reaction product was analyzed by gas chromatography.

The yield of 3-hydroxy-4,5-dimethoxybenzaldehyde was 83%.

Example 3 Example 1 except that the solvent was changed from acetone to dioxane
reacted in the same way.

The reaction product was analyzed by gas chromatography.

The yield of 3-hydroxy-4,5-dimethoxybenzaldehyde was 79%.

Comparative Example 1 8.4 jj (50 mmol) of 3.4-dihydroxy-5-methoxybenzaldehyde was dissolved in 50 ml of IN aqueous sodium hydroxide solution, and 6,7 ml of dimethyl sulfate was added while stirring.
g (55 mmol) was added dropwise.

After reacting at room temperature for 24 hours, the mixture was made slightly acidic with dilute hydrochloric acid, extracted with ether, and the extract was analyzed by gas chromatography.

The yield of 3-hydroxy-4,5-dimethoxybenzaldehyde is 40%, the yield of 3,4.5-trimethoxybenzaldehyde is 10%, and the yield of syringaldehyde is 8%.
He was in charge.

Comparative Example 2 As an alkaline agent, I
The reaction was carried out in the same manner as in Comparative Example 1 except that an N-potassium aqueous solution was used.

The reaction product was analyzed by gas chromatography.

The yield of 3-hydroxy-4,5-dimethoxybenzaldehyde was 40%, the yield of 3.4.5-trimethoxybenzaldehyde was 17fo, and the yield of syringaldehyde was 13%.

Example 4 6.9 g (50
mmol), dimethyl sulfate 6.59 (55 mmol)
and 6.0 g (57 mmol) of sodium carbonate were added to 8 OrrLl of acetone and reacted for 4 hours at reflux temperature.

The reaction product was analyzed by gas chromatography. The yield of 3-hydroxy-4-methoxybenzaldehyde was 87%.
The yield of 3-methoxyl 4-hydroxybenzaldehyde was 5%, and the yield of veratrumaldehyde was 3%.

Example 5 Example 4 except that the solvent was changed from acetone to dioxane
Similarly, the reaction was carried out at 100°C for 2 hours.

The reaction product was analyzed by gas chromatography.

The yield of 3-hydroxy-4-methoxybenzaldehyde was 85%.

Example 6 A reaction was carried out at 100° C. for 2 hours in the same manner as in Example 4 except that the solvent was changed from acetone to dimethyl sulfoxide.

The reaction product was analyzed by gas chromatography.

The yield of 3-hydroxy-4-methoxybenzaldehyde was 90%.

Claims (1)

[Claims] 1. 1 to 1.2 mol of dimethyl sulfuric acid per 1 mol of the 3,4-dihydroxybenzaldehyde compound represented by the general formula; (R in the formula represents a hydrogen atom or an alkoxy group) (However, R in the formula has the same meaning as above). A method for producing a 3-hydroxy-4-methoxybenzaldehyde compound.