JP3500895B2 - Method for producing 3,4-dihydroxy-5-nitrobenzaldehyde - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to 3-alkoxy-
3-from 4-hydroxy-5-nitrobenzaldehyde
The present invention relates to a method for producing 4-dihydroxy-5-nitrobenzaldehyde in high yield and safely. 3,4-Dihydroxy-5-nitrobenzaldehyde is a compound useful as a synthetic raw material for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art 3-Alkoxy-4-hydroxy-5-
A method of dealkylating nitrobenzaldehyde to produce 3,4-dihydroxy-5-nitrobenzaldehyde is a method of refluxing 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde in concentrated hydrobromic acid and acetic acid. It is known (Japanese Patent Laid-Open Nos. 63-150237 and 63-170311). However, in this method, a by-product (2-
There is a problem that bromo-3,4-dihydroxy-5-nitrobenzaldehyde or a black decomposition product is produced. Further, this method has a problem that toxic methyl bromide is generated.

Further, a raw material (for example, 3-methoxy-4-)
Hydroxy-5-nitrobenzaldehyde) and the target product (3,4-dihydroxy-5-nitrobenzaldehyde) were subjected to thermal analysis. As a result, 3-methoxy-4-hydroxy-5-nitrobenzaldehyde and 3,4-dihydroxy-5 183.5 with nitrobenzaldehyde
A large exothermic peak starting from ° C was observed. This suggests that the safety of these compounds must be taken into consideration when producing 3,4-dihydroxy-5-nitrobenzaldehyde from 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde. It is believed that Therefore, it is considered desirable to carry out this reaction at a low temperature, and it is hard to say that the above-mentioned known production method is a preferable method from this point as well.

Another method is to use the thiolate anion of an aromatic mercapto compound to produce 3-methoxy-4.
A method for dealkylating -hydroxy-5-nitrobenzaldehyde is known (Japanese Patent Publication No. 6-509064). However, this method also has a high reaction temperature (130 ° C.) like the above-mentioned method and is not satisfactory in terms of safety.

[0005]

In view of the above technical background, the present invention provides 3-alkoxy-4-hydroxy-
Dealkylation of 5-nitrobenzaldehyde to give 3,4-
In a method for producing dihydroxy-5-nitrobenzaldehyde, the production of 3,4-dihydroxy-5-nitrobenzaldehyde can be performed while suppressing the progress of side reactions (that is, at high yield) and safely (that is, at low reaction temperature). Industrially suitable 3,4-dihydroxy-5 which can be
-To provide a method for producing nitrobenzaldehyde.

[0006]

The object of the present invention is to dealkylate 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde to produce 3,4-dihydroxy-5-nitrobenzaldehyde. This is achieved by a method for producing 3,4-dihydroxy-5-nitrobenzaldehyde characterized in that the reaction is carried out in the presence of aluminum chloride and a base.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below. As 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde, the alkoxy group has 1 to 8 carbon atoms.
A compound that is an alkoxy group consisting of an alkyl group of is used. As the alkyl group, for example, a methyl group,
Ethyl group, n-propyl group, iso-propyl group, n-
Butyl group, iso-butyl group, sec-butyl group, te
Examples thereof include lower alkyl groups such as rt-butyl group and cycloalkyl groups such as cyclopentyl group and cyclohexyl group.

As 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde, specifically, 3-methoxy-4-hydroxy-5-nitrobenzaldehyde, 3
-Ethoxy-4-hydroxy-5-nitrobenzaldehyde, 3-n-propoxy-4-hydroxy-5-nitrobenzaldehyde, 3-iso-propoxy-4-hydroxy-5-nitrobenzaldehyde, 3-n-butoxy-4-. Hydroxy-5-nitrobenzaldehyde,
Examples thereof include 3-iso-butoxy-4-hydroxy-5-nitrobenzaldehyde, 3-sec-butoxy-4-hydroxy-5-nitrobenzaldehyde, 3-tert-butoxy-4-hydroxy-5-nitrobenzaldehyde and the like.

An organic base is preferably used as the base. Examples of the organic base include pyridine compounds such as pyridine and N, N-dimethylpyridine, aliphatic tertiary amines such as trimethylamine, triethylamine and diisopropylethylamine, aniline, toluidine, N-methylaniline, dimethylaniline and diphenylamine.
At least one aryl group such as triphenylamine or phenylenediamine bound to a nitrogen atom, or at least cyclopropylamine, cyclobutylamine, cyclohexylamine, methylcyclohexylamine, cyclopropyldimethylamine, cyclobutyldimethylamine or the like. Examples thereof include cycloalkylamine in which one cycloalkyl group is bonded to a nitrogen atom. Among these organic bases, pyridine compounds and aliphatic tertiary amines are preferable, and pyridine compounds are particularly preferable. The organic base is 3-alkoxy-4-hydroxy-5.
-It is preferable to use 1 to 10 mol, particularly 1 to 5 mol, per 1 mol of nitrobenzaldehyde. When the amount of the organic base used is small, the reaction becomes very slow, and when the amount of the organic base used is large, purification of the target product becomes difficult, which is not preferable.

An anhydride is preferably used as aluminum chloride, and the amount thereof is, for example, 3-alkoxy-4.
-Hydroxy-5-nitrobenzaldehyde is 1 to 5 mol, preferably 1 to 2 mol, per 1 mol.

In the present invention, the dealkylation reaction of 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde is carried out in the presence of aluminum chloride and an organic base at 25-1.
It is carried out at low reaction temperatures of 00 ° C, preferably 30-85 ° C. By carrying out the reaction at such a low reaction temperature, it is possible to avoid the above-mentioned problems relating to safety and to suppress the production of by-products that are difficult to purify. The reaction pressure is not particularly limited, and the reaction is performed under normal pressure, for example. The reaction atmosphere is preferably an inert gas (argon, nitrogen, etc.) atmosphere.

The above dealkylation reaction is preferably carried out in the presence of a reaction solvent. Examples of the reaction solvent include aliphatic halogenated hydrocarbons such as dichloromethane, dichloroethane, chloroform and carbon tetrachloride; ethers such as tetrahydrofuran and 1,4-dioxane; aromatic carbonization such as benzene, toluene and xylene. Hydrogen or the like is preferably used, but the reaction solvent is not particularly limited as long as it does not hinder the progress of the reaction. The reaction solvent is, for example, 0.1 to 10 L per mol of 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde.
(Liter), preferably 1 to 5 L (liter) is used.

After completion of the reaction, the reaction solution obtained by the dealkylation reaction is treated with an aqueous acid solution. This process is -20 to 80
C., preferably 0-50.degree. At this time, the pressure is not particularly limited, and for example, the treatment is performed under normal pressure, but the atmosphere is preferably an inert gas (argon, nitrogen, etc.) atmosphere. As the acid aqueous solution, hydrochloric acid, sulfuric acid,
An aqueous solution of an inorganic acid such as nitric acid is preferably used, among which hydrochloric acid is preferred. The aqueous acid solution is used in an amount of, for example, 1 to 20 mol, preferably 1 to 10 mol, per 1 mol of 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde charged. When hydrochloric acid is used as the acid aqueous solution, for example, 5-37 wt% hydrochloric acid can be used. Next, 3,4-dihydroxy-5-nitrobenzaldehyde is recovered from the reaction solution treated with the acid aqueous solution by extraction, crystallization and the like.

[0014]

EXAMPLES Next, the present invention will be specifically described with reference to examples. The yield (mol%) of 3,4-dihydroxy-5-nitrobenzaldehyde was calculated based on 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde.

Example 1 Tetrahydrofuran (25 m
l) and anhydrous aluminum chloride (55.80 mmol)
Was charged, and pyridine (111.63 mmol) was added dropwise at room temperature while stirring the solution in an argon stream. Then, 3-methoxy-4-hydroxy-5-nitrobenzaldehyde (50.72 mmol) was added, and the mixture was heated under reflux for 1 hour (reaction temperature 65 ° C), and then the reaction solution was cooled to room temperature. 6N Hydrochloric acid (50 ml) was added to the obtained reaction liquid, the mixture was stirred at room temperature for 1 hr in an argon stream, and then extracted with ethyl acetate (150 ml). Then, the obtained organic layer was washed with saturated saline (50 ml) three times, dried over anhydrous sodium sulfate, and then the solvent was distilled off to obtain crystals. The crystals were dried under reduced pressure to give 3,4-dihydroxy-
5-Nitrobenzaldehyde was obtained with a yield of 93%. All these operations were performed under normal pressure.

Example 2 Tetrahydrofuran was added to 1,2-dichloroethane (40 m
The same operation as in Example 1 was performed except that the reaction temperature was changed to 80 ° C. instead of 1). As a result, the yield of 3,4-dihydroxy-5-nitrobenzaldehyde was 94%.

Example 3 Tetrahydrofuran was added to 1,2-dichloroethane (40 m
l) and pyridine instead of triethylamine (111.6
3 mmol), the reaction temperature was changed to 80 ° C., and the reaction time was changed to 4 hours, except that the same operation as in Example 1 was performed. As a result, the yield of 3,4-dihydroxy-5-nitrobenzaldehyde was 76%.

Example 4 Tetrahydrofuran was changed to methylene chloride (100 ml), the amount of pyridine was changed to 223.26 mmol, the reaction temperature was changed to 40 ° C., and the reaction time was changed to 9 hours.
The same operation as in Example 1 was performed. As a result, the yield of 3,4-dihydroxy-5-nitrobenzaldehyde was 88.
%Met.

Example 5 Tetrahydrofuran was changed to carbon tetrachloride (100 ml), the amount of pyridine was changed to 223.26 mmol, the reaction temperature was changed to 77 ° C., and the reaction time was changed to 3 hours.
The same operation as in Example 1 was performed. As a result, the yield of 3,4-dihydroxy-5-nitrobenzaldehyde was 85.
%Met.

Example 6 3-methoxy-4-hydroxy-5-nitrobenzaldehyde was replaced with 3-ethoxy-4-hydroxy-5-nitrobenzaldehyde (50.72 mmol), and the reaction time was changed to 11 hours. The same operation as in Example 1 was performed. As a result, the yield of 3,4-dihydroxy-5-nitrobenzaldehyde was 74%. The results of the examples are shown in Table 1.

[0021]

[Table 1]

[0022]

INDUSTRIAL APPLICABILITY According to the present invention, in a method for producing 3,4-dihydroxy-5-nitrobenzaldehyde by dealkylating 3-alkoxy-4-hydroxy-5-nitrobenzaldehyde, the side reaction is suppressed ( That is, with high yield) and safely (ie, at low reaction temperature)
3,4-Dihydroxy-5-nitrobenzaldehyde can be prepared. INDUSTRIAL APPLICABILITY The present invention is an industrially suitable method for producing 3,4-dihydroxy-5-nitrobenzaldehyde because it is a highly safe method that hardly produces by-products that are difficult to purify.

─────────────────────────────────────────────────── ─── Continuation of the front page (56) Reference JP-A-63-44546 (JP, A) JP-A-63-150237 (JP, A) Special table 10-505849 (JP, A) Special table 6- 509064 (JP, A) (58) Fields surveyed (Int.Cl. ⁷ , DB name) C07C 201/12 C07C 205/44

Claims (7)

(57) [Claims] 1. 3-Alkoxy-4-hydroxy-5-
A method for producing 3,4-dihydroxy-5-nitrobenzaldehyde by dealkylating nitrobenzaldehyde, wherein the dealkylation reaction is carried out in the presence of aluminum chloride and a base. A method for producing benzaldehyde. 2. The method for producing 3,4-dihydroxy-5-nitrobenzaldehyde according to claim 1, wherein the base is an organic base. 3. The organic base is a pyridine compound or an aliphatic 3
The amine according to claim 3, which is a primary amine.
-Method for producing dihydroxy-5-nitrobenzaldehyde. 4. The method for producing 3,4-dihydroxy-5-nitrobenzaldehyde according to claim 1, wherein the dealkylation reaction is carried out at 25 to 100 ° C. 5. The method for producing 3,4-dihydroxy-5-nitrobenzaldehyde according to claim 1, wherein the dealkylation reaction is carried out in the presence of a reaction solvent. 6. The 3,4-dihydroxy according to claim 1, wherein the reaction solution obtained by the dealkylation reaction is treated with an aqueous acid solution to recover 3,4-dihydroxy-5-nitrobenzaldehyde. A method for producing 5-nitrobenzaldehyde. 7. The method for producing 3,4-dihydroxy-5-nitrobenzaldehyde according to claim 5, wherein the aqueous acid solution is hydrochloric acid.