JP2832584B2 - Method for producing carboxylic acid esters - Google Patents

Description

Description: BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an aromatic or heterocyclic carboxylic acid ester. [0002] As a method for producing an aromatic or heterocyclic carboxylic acid ester, a method of reacting an organic halide, carbon monoxide and a phosphoric acid triamide in the presence of a carbonylation catalyst (JP-A-57-200338). Is known. However, this method does not disclose any reaction with an aromatic chlorinated product in which chlorine is directly substituted on an aromatic ring, and further uses phosphoric triamide for the reaction. This phosphoric triamide is expensive and highly toxic, and therefore has a problem in industrialization. JP-A-61-293950 discloses a method for producing a carboxylic acid or an ester thereof using a chloro or bromoarene carbonyl chromium compound, but it is expensive to produce a tricarbonyl chromium complex as a reaction substrate. However, there is a problem in toxicity. As described above, the reaction between aromatic iodide or bromide and carbon monoxide is known, but a method for synthesizing aromatic carboxylic esters by reacting aromatic chloride and carbon monoxide is completely known. Not. In view of the above situation, the present inventors have conducted intensive studies on the reaction between an aromatic or heterocyclic chloride and carbon monoxide, and have found that aromatic or heterocyclic chloride has a high yield. A method for obtaining heterocyclic carboxylic esters has been established, and the present invention has been completed. Accordingly, an object of the present invention is to provide a method for producing carboxylic acid esters. The present invention provides a compound represented by the general formula (I)
V): embedded image R ¹ (C1) m (IV) (wherein, R ¹ represents an aromatic hydrocarbon group or a heterocyclic hydrocarbon group which may have a substituent, and m is 1 or more. And an organic chloride represented by the formula (V): (In the formula, R ⁵ R ⁶ and R ⁷ may be the same or different and represent an alkyl group optionally having a substituent, a phenyl group, a phenyl group optionally having a substituent, or a phenoxy group. A) a phosphine compound represented by the formula (1) as a catalyst, in the presence of a base, carbon monoxide and the general formula (II): R ⁴ OH (II) (wherein R ⁴ may have a substituent; An aliphatic hydrocarbon group, an aromatic hydrocarbon group or a heterocyclic hydrocarbon group) and an alcohol represented by the formula:
Wherein the reaction is carried out at a reaction temperature of the general formula (I-
1): embedded image This relates to a method for producing a carboxylic acid ester represented by R ^1. (COOR ⁴ ) m (I-1) (wherein R ¹ , R ⁴ and m are the same as described above). is there. [0005] The carboxylic esters according to the present invention are compounds useful as pesticides per se, and also provide a novel method for producing carboxylic esters useful as pharmaceuticals. The reaction of the present invention can be represented, for example, by the following scheme. Embedded image That is, an organic chloride represented by the general formula (IV) is catalyzed by a palladium compound and a phosphine compound represented by the general formula (V) in the presence of a base, in the presence or absence of a solvent, or in the absence of a solvent. By reacting with carbon and an alcohol represented by the general formula (II) at a reaction temperature of 180 ° C. to 300 ° C., the desired general formula (I-1)
Can be produced. The organic chloride represented by the general formula (IV) of the present invention has at least one chlorine atom on a ring of an aromatic hydrocarbon or a heterocyclic hydrocarbon which may have a substituent. Any organic chloride may be used, and it also includes condensed ring hydrocarbons and condensed heterocyclic hydrocarbons. Representative examples thereof include, for example, chlorobenzene, dichlorobenzene,
Trichlorobenzene, tetrachlorobenzene, pentachlorobenzene, hexachlorobenzene, trifluoromethylchlorobenzene, chlorotoluene, dichlorotoluene, trichlorotoluene, chloroxylene, dichloroxylene, trichloroxylene, chlorophenol, chloroanisole, chloronitrobenzene, dichloronitrobenzene, chlorocyano Benzene, chlorophenyl acetate, N-acetylchloroaniline, chloroacetophenone, chlorobenzophenone, chloromethylthiobenzene, chlorobenzoate, chlorodiphenyl ether, chloronaphthalene, chloromethylnaphthalene,
Examples thereof include aromatic organic chlorides such as chloroanthraquinone, and heterocyclic organic chlorides such as chlorothiophene, chlorofuran, chloroindole, chloropyridine, dichloropyridine, chloropicoline, chloroquinoline, chloroquinoxaline, and dichloroquinoxaline. The organic chloride may be used in a predetermined amount, or may be used in excess to be used as a solvent. The alcohol represented by the general formula (II) used in the present invention includes, for example, aliphatic alcohols such as methanol, ethanol, propanol and butanol;
Examples include aromatic alcohols such as phenol, halophenol, cresol and xylenol, and heterocyclic hydroxides such as furfuryl alcohol and thienyl alcohol. Alcohols may be used in a predetermined amount as they are, or may be prepared in advance as an alkali metal alcoholate and used. The alcohol represented by the general formula (II) is present in the reaction system in an amount ranging from equimolar to 1 mole of the organic chloride to a number of moles corresponding to the number of chlorine atoms on the ring of the organic chloride or an excess. Good. The palladium compound used as a catalyst in the present invention may be used in combination with a phosphine compound. Examples of the palladium compound include metal palladium and
Palladium carbon, palladium alumina, palladium chloride, palladium bromide, palladium acetate, dichlorobiscyanophenylpalladium, dichlorobistriphenylphosphinepalladium, tetrakistriphenylphosphinepalladium, and the like can be given. The phosphine compound represented by the general formula (V) which can be used in combination with the palladium compound in the present invention includes, for example, triisopropylphosphine, tributylphosphine, triphenylphosphine, triparafluorophenylphosphine, tri-pentafluorophenylphosphine, Triparatolylphenylphosphine, triphenoxyphosphine, dimethylphenylphosphine,
Methyldiphenylphosphine, di-pentafluorophenylphosphine and the like can be mentioned. The addition amount of the phosphine compound is 0.01 to 1 with respect to the palladium compound.
It may be used in a molar amount of 0000 times, and preferably 0.1 to
What is necessary is just to use 100 times mol. In the present invention, a palladium compound and a phosphine compound represented by the general formula (V) may be used in combination, may be used alone in a reaction system, or may be prepared in advance in a complex form and used. . Although the amount of addition is not particularly limited, the amount of palladium compound and phosphine compound added to the reaction system,
It may be used in an amount of 0.0001 to 0.5 times mol per mol of the organic chloride represented by the general formula (IV), preferably from 0.001 to 0.1 times mol. Good. The base which can be used in the present invention may be selected from inorganic bases and organic bases, such as inorganic bases such as sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide, triethylamine, tributylamine, diisopropylethylamine, and the like. Organic bases such as triisooctylamine, pyridine, N-methylpyrrolidine, N-methylmorpholine and N-ethylmorpholine can be mentioned. As the amount of the base to be used, it is preferable to use an amount necessary for neutralizing the produced hydrogen chloride, but of course it may be at least better or larger than this. The reaction in the present invention can be carried out in the presence or absence of a solvent, and any solvent that does not significantly inhibit the reaction may be used, such as hexane, benzene, ether, tetrahydrofuran. , Acetonitrile, dimethylformamide, hexamethylphosphotriamide, acetone and the like. The reaction of the present invention is carried out under normal pressure to pressurization,
The pressure of carbon monoxide is appropriately selected in the range of 1 to 200 atm, and is preferably in the range of 1 to 50 atm. The present invention is carried out at a reaction temperature in the range of 180 ° C to 300 ° C, preferably in the range of 180 ° C to 250 ° C. The reaction vessel used in the present invention may be a commonly used reaction vessel. In the case of a pressurized reaction, any reaction vessel capable of withstanding the reaction pressure may be used, and usually a metal or glass vessel is used. The reaction time is not fixed depending on the amount of the reaction reagent and the reaction temperature, but may be selected from a range of several minutes to 48 hours. After completion of the reaction, the desired compound can be obtained by treating the product by a conventional method. Examples of the present invention will be described below, but the present invention is not limited to these examples. Example 1 Production of diethyl phthalate Orthodichlorobenzene (1.47 g) and ethanol (4.6) were placed in a metal autoclave with an electromagnetic induction stirrer.
g), palladium chloride (35 mg), triphenylphosphine (0.13 g), sodium carbonate (4.2 g) and benzene (15 ml), and after several replacement with carbon monoxide, filling at 50 kg / cm ² , 250 ° C in salt bath
The reaction was performed for 5 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, washed with water, separated into organic layers, and the production rate was measured by gas liquid chromatography (GLC). The target substance, diethyl phthalate, was produced at a production rate of 43%. It was confirmed. Example 2 Preparation of ethyl 4-acyl-benzoate 4-chloroacetophenone (3.1 g, 0.02 mol), 2% Pd in a 100 ml stainless steel autoclave
-C (32 mg), triphenylphosphine (525 m
g), sodium carbonate (2.5 g, 0.024 mo
l), ethanol (4.6 g), and benzene (10 m
l), carbon monoxide is sealed at 20 kg / cm ² ,
The reaction was performed at 200 ° C. for 3 hours. After standing to cool, toluene (50m
l) and water (50 ml) were added to carry out liquid separation. The organic layer was concentrated and then recrystallized from ethyl acetate-hexane to obtain the desired compound. Melting point 51-52 ° C Yield 1.1 g (Yield 29
Example 4 Production of diethyl terephthalate A reaction was carried out in the same manner as in Example 3 except that paradichlorobenzene was used instead of orthodichlorobenzene in Example 3,
It was confirmed that the target substance, diethyl terephthalate, was produced at a production rate of 39%. Example 4 Preparation of ethyl 2-pyridinecarboxylate 2-chloropi in a 100 ml stainless steel autoclave
Lysine (2.3 g, 0.02 mol), 2% Pd-C (3
2 mg), triphenylphosphine (525 mg), charcoal
Sodium (2.5 g, 0.024 mol), ethanol
(4.6) and benzene (10 ml)
Enclose carbon at 20 kg / cm ² and react at 200 ° C for 4 hours
Responded. After standing to cool, toluene (50 ml) and water (50
ml), and the mixture is separated.
(GLC) to determine the production rate,
That ethyl carboxylate is produced at a rate of 51%
And confirmed.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07D 209/04 C07D 209/04

Claims (1)

(57) [Claims] An organic chloride having at least one chlorine atom on a ring of an aromatic hydrocarbon or a heterocyclic hydrocarbon which may have a substituent is converted to a palladium compound and a compound represented by the general formula (V): (In the formula, R ⁵ R ⁶ and R ⁷ may be the same or different and represent an alkyl group optionally having a substituent, a phenyl group, a phenyl group optionally having a substituent, or a phenoxy group. ) As a catalyst, and in the presence of a base, carbon monoxide and alcohols at 180 ° C to 300 ° C.
A method for producing carboxylic acid esters, characterized by reacting at a reaction temperature of 2. 2. The method for producing a carboxylic acid ester according to claim 1, wherein the palladium compound is a palladium metal, a palladium metal supported on a solid, or a palladium zero-, di- or tetravalent complex. 3. The method for producing a carboxylic acid ester according to claim 1, wherein the palladium compound is palladium carbon, palladium chloride or palladium acetate. 4. The method for producing a carboxylic acid ester according to claim 1, wherein the phosphine compound represented by the general formula (V) is a trialkylphosphine or a triarylphosphine. 5. The method for producing a carboxylic acid ester according to claim 1, wherein the base is an inorganic base or an organic base. 6. 5. The method for producing a carboxylic acid ester according to claim 1, wherein the base is sodium carbonate or potassium carbonate. 7. The method for producing a carboxylic acid ester according to claim 1, wherein the pressure of carbon monoxide is 1 to 200 atm.