JP3528204B2 - Method for producing 2-carboxy-benzo-4-pyrones - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing 2-carboxy-benzo-4-pyrones using an aromatic hydrocarbon compound as a solvent. 2. Description of the Related Art As a process for producing 2-carboxy-benzo-4-pyrones, an alcoholate is used in an alcoholic solvent, followed by condensation with another ester and then using an acid. Is known to close the ring,
In this method, there is an industrial problem that the raw material remains depending on the amount of the solvent, or a large amount of high-concentration alcohol-containing wastewater is generated after the product is taken out, and when an acid containing water is used during the ring closure reaction, There was a problem that carboxylic acid was produced as a by-product. The inventors of the present invention have made intensive studies to solve such problems, and as a result, by using an aromatic hydrocarbon compound as a solvent, it is possible to synthesize a chromone skeleton very efficiently and at the same time reduce the wastewater load. The present inventors have found that it can be greatly reduced, and have further made various studies to arrive at the present invention. DISCLOSURE OF THE INVENTION [0004] The present invention relates to 2-hydroxyacetophenones.
In obtaining the pyrones, at least one kind of aromatic hydrocarbon compounds such as alkylbenzene, pyridine, and chlorobenzene is used as a solvent, and at least one selected from concentrated sulfuric acid, hydrogen chloride gas, methanesulfonic acid, and glacial acetic acid upon ring closure. It is intended to provide an industrially excellent method for producing 2-carboxy-benzo-4-pyrones using a kind of acid. That is, the present invention relates to a compound represented by the general formula (1): (Wherein X is a hydroxy group, a nitro group, a halogen atom,
Indicates a hydrogen atom or RCONH. Here, R is an alkyl group having 1 to 20 carbon atoms which may be substituted by a phenyl group, or Is shown. Here, R ″ represents an alkyl group having 1 to 10 carbon atoms which may be substituted by a phenyl group, or an alkoxy group having 2 to 10 carbon atoms which may be substituted by a phenyl group. ) Is reacted with an alcoholate and an oxalic acid diester in an aromatic hydrocarbon solvent to obtain a compound represented by the general formula (2): (Wherein X has the same meaning as described above, and R ′ represents a lower alkyl group). Then, the obtained compound (2) is isolated without isolation. Dark inside
Choose from sulfuric acid, hydrogen chloride gas, acetic acid, methanesulfonic acid
Wherein at least one type of anhydrous acid is acted upon. (Wherein X and R ′ have the same meanings as described above.) The present invention provides a method for producing 2-carboxy-benzo-4-pyrones represented by the formula: Hereinafter, the present invention will be described in detail. The 2-hydroxyacetophenones (1) used in the present invention include 2-hydroxyacetophenone, 5-hydroxyacetophenone,
Bromo-2-hydroxy-acetophenone, 5-nitro-2-hydroxy-acetophenone, 3- {4- (4-
Phenyl-1-butoxy) benzoyl {amino-2-hydroxy-acetophenone, 3-acetoamino-2-hydroxyacetophenone, 3-butyroylamino-2-
Hydroxyacetophenone, 3-pentatesiloylamino-2-hydroxyacetophenone, 3- (4-phenylbutyroyl) amino-2-hydroxyacetophenone. The present invention is characterized in that an aromatic hydrocarbon compound is used as a solvent. Examples of such a solvent include hydrocarbons such as benzene, toluene, xylene and ethylbenzene, and nitrated hydrocarbons such as nitrobenzene. And halogenated hydrocarbons such as chlorobenzene and dichlorobenzene, and pyridines such as pyridine and 2-methyl-5-ethylpyridine. Further, it is used as a mixture with aliphatic hydrocarbons such as pentane, hexane, heptane and the like, and ethers such as dioxane, tetrahydrofuran and tert-butyl methyl ether. The amount of use is usually about 1 to 50 times the weight of the 2-hydroxyacetophenones (1). As the alcoholate used in the present invention, an alcoholate such as sodium or potassium methylate, ethylate, tertiary butoxide or a mixture thereof is used. The alcoholate may be an alcohol solution. The amount of alcoholate used is 2-
Usually 2 to 10 for hydroxyacetophenones (1)
It is molar times. As the oxalic acid diester as the other reaction reagent, for example, diethyl or dimethyl ester of oxalic acid is used, and its amount is usually 1 to 10 mol based on 2-hydroxyacetophenones (1). It is twice. [0012] The reaction temperature is usually 200 ° C or lower, preferably -50 to 150 ° C. The progress of the reaction can be confirmed by analytical means such as liquid chromatography, and the reaction end point can usually be determined by disappearance of 2-hydroxyacetophenones (1). After completion of the above reaction, the reaction mixture is selected from concentrated sulfuric acid, hydrogen chloride gas, acetic acid, and methanesulfonic acid. At least one anhydrous acid is added to close the ring. The amount of the acid used is usually 10 mol times or less of the alcoholate used, preferably 1 to 5 mol times of the alcoholate. The reaction temperature of this reaction is usually not higher than 200 ° C, preferably -50 to 100 ° C.
After confirming the completion of the reaction by an analytical means such as liquid chromatography, water is added to the reaction mixture, and the mixture is separated as it is to obtain the desired product from the organic layer. Thus, 2-carboxyl-benzo-4
-The pyrones (3) can be obtained, but according to the method of the present invention, the load of drainage can be greatly reduced, and the reaction can proceed extremely efficiently even under mild conditions. -It is advantageous as a method for producing benzo-4-pyrones. EXAMPLES Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples. Example 1 Under a nitrogen atmosphere, 8.36 g of 2-hydroxy-acetophenone
To a solution of (61.4 mmol) in 200 ml of toluene was added 9.42 g (79.8 mmol) of dimethyl oxalate and 35.5 g (184 mmol) of a 28% methylate methanol solution.
After stirring for 0.5 hour, 12.4 g (123 mmol) of 98% concentrated sulfuric acid was added, and the mixture was stirred at 60 ° C for 0.5 hour. Then 140 g
Water was added, and the resulting organic layer was concentrated.
4.0 g was added and the mixture was filtered at 10 ° C. or lower to obtain 12.5 g of 2-methoxycarbonyl -benzo- 4-pyrone. mp. 117-119
C, 98% yield. Examples 2 to 4 The procedure of Example 1 was repeated, except that chlorobenzene, nitrobenzene and 2-methyl-5-ethyl-pyridine were used instead of toluene as the solvent. Carbonyl -benzo -4-pyrone was obtained. Table 1 shows the results. [Table 1] Examples 5 to 11 In Example 1, 2,6-dihydroxyacetophenone, 5-bromo-2-hydroxy-acetophenone, 5-nitro-
Using 2-hydroxy-acetophenone, 3- {4- (4-phenyl-1-butoxy) benzoyl} amino-2-hydroxy-acetophenone, dimethyl oxalate / methylate, diethyl oxalate / ethylate or di-tert-butyl oxalate / tersia The procedure was performed in the same manner as in Example 1 except that leave butylate was used. All gave good results. Table 2 shows the results. [Table 2] Examples 12 to 14 The procedure of Example 8 was repeated, except that hydrogen chloride gas, methanesulfonic acid and acetic acid were used instead of concentrated sulfuric acid. The results are shown in Table 3. Reference Example The procedure of Example 8 was repeated, except that 35% hydrochloric acid was used instead of concentrated sulfuric acid. The results are shown in Table 3. [Table 3]

──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Tsutomu Matsumoto 2-10-1 Tsukahara, Takatsuki-shi, Osaka Sumitomo Chemical Industries Co., Ltd. (72) Inventor Masayoshi Minami 2-10-1 Tsukahara, Takatsuki-shi, Osaka Sumitomo (56) References JP-A-2-218675 (JP, A) JP-A-3-95144 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) C07D 311 / 24 CA (STN) CAOLD (STN) REGISTRY (STN)

Claims (1)

(57) [Claims] [Claim 1] The general formula (1) (Wherein X is a hydroxy group, a nitro group, a halogen atom,
Indicates a hydrogen atom or RCONH. Here, R is an alkyl group having 1 to 20 carbon atoms which may be substituted by a phenyl group, or Is shown. Here, R ″ represents an alkyl group having 1 to 10 carbon atoms which may be substituted by a phenyl group, or an alkoxy group having 2 to 10 carbon atoms which may be substituted by a phenyl group. ) Is reacted with an alcoholate and an oxalic acid diester in an aromatic hydrocarbon solvent to obtain a compound represented by the general formula (2): (Wherein X has the same meaning as described above, and R ′ represents a lower alkyl group). Then, the obtained compound (2) is isolated without isolation. Dark inside
Choose from sulfuric acid, hydrogen chloride gas, acetic acid, methanesulfonic acid
Wherein at least one type of anhydrous acid is acted upon. (Wherein X and R ′ have the same meanings as described above.) A method for producing 2-carboxy-benzo-4-pyrones represented by the formula: