JP2762431B2 - Production method of aromatic carboxylic acid ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel process for producing an aromatic carboxylic acid ester. Aromatic carboxylate esters have a very wide range of uses, for example, as pharmaceuticals, pesticides, dye / pigment intermediates, polymer raw materials, plasticizers and preservatives.

[0002]

2. Description of the Related Art Conventional methods for producing an aromatic carboxylic acid ester include, for example, an aromatic carboxylic acid or a derivative thereof (a carboxylic acid salt, an acid halide or an acid anhydride) and an alcohol or a derivative thereof. A method of producing an esterified product by reaction is generally used.

[0003] However, in this method, it is often difficult to efficiently produce an aromatic carboxylic acid having a carboxyl group at a specific position with high purity, and it becomes a raw material in the above-mentioned general production method. However, there has been a problem that an aromatic carboxylic acid having a high-purity substituent may not be obtained freely.

[0004] Another method for producing an aromatic carboxylic acid ester is to prepare an aromatic halide (iodide, chlorinated or brominated), an alcohol and carbon monoxide in the presence of a palladium catalyst, a nickel catalyst or the like. , A method of synthesizing under high temperature and high pressure (J. Org. Chem. 39 (N
o. 23) 3318 (1974), Bull. Che
m. Soc. Jpn. 48 (No. 7) 2075 (19
75)) are known.

[0005] However, this known production method has problems that the reaction yield is low, the selectivity is low, it is difficult to recover expensive catalyst components, and toxic compounds are produced from the catalyst components. However, it was not always satisfactory industrially.

In the above-mentioned known production method, the reaction is carried out by using a palladium catalyst together with a second component such as an amine compound in order to improve the yield of the aromatic carboxylic acid ester. In such a case, the second component has a problem in that, in addition to the reaction for generating an aromatic carboxylic acid ester, a reaction in which by-products other than the acid ester (for example, an amide compound) are considerably by-produced occurs. .

[0007]

SUMMARY OF THE INVENTION An object of the present invention is to provide an industrial method for producing an aromatic carboxylic acid ester which can solve the problems of the conventionally known methods.

[0008]

SUMMARY OF THE INVENTION The present invention relates to an aromatic bromide, an alcohol and carbon monoxide, comprising at least one of alkali metal salts and alkaline earth metal salts of phenols (second component); Palladium catalyst (first component)
A process for producing an aromatic carboxylic acid ester, characterized by reacting in the presence of

The process of the present invention generally uses a reaction carried out according to the following reaction formula I. An aromatic carboxylic acid ester is synthesized by reacting an aromatic bromide, an alcohol, and carbon monoxide in the presence of a catalyst of at least one of an alkali metal salt and an alkaline earth metal salt of a phenol and palladium metal. If necessary,
After completion of the reaction, neutralization is performed to convert compound IV into an aromatic carboxylic acid ester having a hydroxyl group or the like.

[0010]

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In the above formula, R ₀ represents an alkyl group, an alkenyl group, an aryl group, a cycloalkyl group, an alkoxy group,
From the group consisting of phenoxy, acyl, nitro, formyl, amino, carboalkoxy, hydroxyl, alkali metal salts of hydroxyl, alkaline earth metal salts of hydroxyl, carboxyl, chlorine and bromine It represents at least one selected atom and atomic group, and n represents an integer of 0 to 4.

In the above formula, R ₁ is an alkyl group, an alkenyl group, an aryl group, a cycloalkyl group, an alkoxy group,
Phenoxy group, acyl group, nitro group, formyl group, amino group, carboalkoxy group, hydroxyl group, alkali metal salt of hydroxyl group, alkaline earth metal salt of hydroxyl group, carboxyl group, alkali metal salt of carboxyl group, carboxyl group At least one selected from the group consisting of an alkaline earth metal salt, a chlorine atom and a (—COOR ′) group (wherein R ₁ corresponds to R ′ of the alcohol (R′OH) (II) in each reaction formula) Represents atoms and atomic groups.

In the above formula, R ′ in R′OH (III) represents a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an i-butyl group, a pentyl group,
It represents an alkyl group having 1 to 10 carbon atoms such as hexyl group and octyl group, a cycloalkyl group having 5 to 10 carbon atoms such as cyclopentyl group and cyclohexyl group, and an arylalkyl group such as phenylmethyl group and phenylethyl group.

The following reaction formula II shows that an aromatic compound wherein R ₂ is an “inactive substituent for this reaction” other than a carboxyl group, a hydroxyl group, an alkali metal salt of a hydroxyl group or an alkaline earth metal salt of a hydroxyl group. It is a reaction formula when group bromide (I ₁ ) is used as a reaction raw material.

[0015]

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In the following reaction formula III, R ₂ in the reaction formula II is a substituent (-OM) of an alkali metal salt of a hydroxyl group or an alkaline earth metal salt of a hydroxyl group.
Is a reaction formula in the case of using an aromatic bromide (I ₂ ) having 1 to 4 as a reaction raw material. In this case, even if the alkali metal salt and alkaline earth metal salt of phenol are not added as the second component, the aromatic bromide also acts as the alkali metal salt and alkaline earth metal salt of phenol. The aromatic carboxylic acid ester (I
V ₂ ), and if necessary, after completion of the reaction, neutralization may be performed to convert IV ₂ into an aromatic carboxylic acid ester having a hydroxyl group.

[0017]

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The following reaction formula IV represents the R in the reaction formula I
_This is a reaction formula in the case where an aromatic bromide (I ₃ ) in which ₀ is a hydroxyl group (—OH) is used as a reaction raw material. The aromatic carboxylic acid ester (IV ₃ ) can be produced, and if necessary, after completion of the reaction, the compound IV ₃ can be neutralized to give a hydroxyl group-containing aromatic carboxylic acid ester.

[0019]

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As the aromatic bromide used in the production method of the present invention, for example, bromobenzene, o-bromotoluene, m-bromotoluene, p-bromotoluene, p-bromostyrene, 4-bromobiphenyl, o-bromotoluene Methoxybromobenzene, m-methoxybromobenzene, p-methoxybromobenzene, 2,4-dimethoxybromobenzene, 2,5-dimethoxybromobenzene, 4-bromoveratrol, p-phenoxybromobenzene, m-bromoacetophenone, acetic acid p-bromophenyl, p-nitrobromobenzene, m-cyanobromobenzene, p-bromobenzaldehyde, p-bromoaniline, methyl p-bromobenzoate, p-dibromobenzene, m-chlorobromobenzene, p-chlorobromobenzene , 4-bromosalicylalde De, 4-bromo-5 nitroveratrol, 4-bromo-5-aromatic bromide with inert groups for this reaction, such as methyl resveratrol _{(R 2),}
aromatic bromides having a hydroxyl group such as o-bromophenol, m-bromophenol, p-bromophenol, 4-bromocatechol, 4-bromoresorcinol, 2-bromohydroquinone, 5-bromoguaiacol, 4-bromoguaiacol, Aromatic bromide having a substituent of an alkali metal salt of a hydroxyl group such as sodium p-bromophenoxide, o-dibromobenzene, p
-Dibromobenzene, m-dibromobenzene, 4,4 '
Aromatic bromides having a plurality of bromine atoms, such as dibromobiphenyl, are preferred.

When an aromatic chlorinated compound having no bromine atom is used, no aromatic carboxylic acid ester is formed under the reaction conditions of the present invention. Further, in the production method of the present invention, when an aromatic bromide having a plurality of bromine atoms is used as a reaction raw material, an aromatic dicarboxylic acid ester is produced.

The alcohol used in the production method of the present invention may be a primary, secondary or tertiary alcohol having 1 to 10 carbon atoms, such as methanol, ethanol, 1-propanol, 2-propanol. Propanol, 1-butanol, 2-butanol, iso-butanol, t-butanol, 1-pentanol, 2-pentanol, 1-
Hexanol, 2-hexanol, 1-octanol,
Examples thereof include 2-ethylhexanol, cyclopentanol, cyclohexanol, allyl alcohol, crotyl alcohol, benzyl alcohol, 2-phenylethanol, and cinnamyl alcohol. Particularly, an aliphatic primary or secondary alcohol having 1 to 6 carbon atoms is preferable.

In the production method of the present invention, alcohol may be used as a reaction solvent, and the amount of alcohol used may be any amount sufficient to dissolve the aromatic bromine compound.
Although it may be in excess with respect to the aromatic bromide,
In the present invention, 0.5 to 1 mol of the aromatic bromide is used.
It is preferable to use the alcohol in an amount of about 20 mole times.

The carbon monoxide used in the process of the present invention is
Although high-purity carbon monoxide may be used, for example, a mixed gas diluted with an inert gas such as nitrogen gas or carbon dioxide gas may be used.

In the production method of the present invention, the pressure (reaction pressure) of the reaction system is 10 kg / cm ² or less, preferably about normal pressure. If the reaction pressure is too high, the reactivity decreases, and the yield of the desired product is significantly reduced, which is not preferable.

The metal palladium catalyst used in the production method of the present invention can be used alone, but the metal palladium may be used by being supported on a porous carrier such as activated carbon, graphite, alumina, silica alumina, or molecular sieve. Can be.

The amount of the palladium metal to be used is preferably an amount of 0.01 to 10% by weight, particularly 0.05 to 5% by weight of the palladium metal with respect to the aromatic bromide.

As the alkali metal salt or alkaline earth metal salt of a phenol used in the production method of the present invention, for example, phenol, o-cresol, m-cresol, p-
-Alkali metal salts such as sodium salt, potassium salt, cesium salt, magnesium salt, calcium salt, barium salt such as cresol, o-bromophenol, p-bromophenol, o-hydroxylbenzoic acid ester and p-hydroxylbenzoic acid ester Or alkaline earth metal salts and the like. In particular, potassium salts, sodium salts,
Calcium salts and the like are preferred.

When an alkaline earth metal salt is used as the phenol salt used in the production method of the present invention, either a monophenol salt or a diphenol salt may be used.

When a hydroxyl-substituted aromatic bromide is used as the aromatic bromide used in the production method of the present invention, an alkali metal salt or an alkaline earth metal salt of the corresponding hydroxyl-substituted aromatic bromide is used. In addition, since there are few types of unreacted substances in the reaction solution, the reaction products can be easily separated.

The amount of the phenol salt to be used is 0.1 to 10 times, especially 0.3 to 5 times, the mole of the aromatic bromide. Is preferred.

In the production method of the present invention, as the reaction solvent, alcohol can be used as the reaction solvent as described above, and it is not necessary to use another solvent. However, if necessary, diethyl ether, diethylene glycol diethyl ether can be used. Ether, tetrahydrofuran, ether solvents such as 1,4-dioxane, benzene, toluene, xylene,
Aromatic hydrocarbon solvents such as nitrobenzene and chlorobenzene, nitrile solvents such as acetonitrile and benzonitrile or N, N-dimethylacetamide, N, N-
Dimethylformamide, dimethylsulfoxide, N-
Methyl-2-pyrrolidone, hexamethylphosphoramide and the like can be used.

In the process of the present invention, the reaction temperature is 5
To 250 ° C, particularly preferably about 50 to 200 ° C. In the production method of the present invention, in particular, the reaction temperature;
The reaction can be sufficiently performed even under mild conditions such as 50 ° C. and a reaction pressure of 0.1 to 5 kg / cm ² , and substantially no by-products are formed. Can be manufactured.

After completion of the reaction, the synthesized product of the present invention is neutralized with a mineral acid salt such as hydrochloric acid, and if necessary, after extraction with a solvent, can be easily separated and purified from the reaction solution by a general method such as distillation under reduced pressure. it can.

[0035]

Next, the present invention will be described in more detail with reference to examples and comparative examples. However, the present invention is not limited to the following examples unless it exceeds the gist of the present invention.

Example 1 In a 100 ml glass flask equipped with a gas inlet tube and a cooling tube, 10.85 g of 4-bromoveratrol, 6.38 g of sodium phenoxide, and 0.00.5% of 10% Pd-C.
3 g and 1-butanol 40 ml were charged, the reaction pressure was reduced to normal pressure (1 kg / cm ² ), and then carbon monoxide (C
(O concentration: 100% by volume) was supplied to the flask at a flow rate of 4 l / hr to flow through the reaction solution, and while the reaction solution was being stirred, the reaction temperature was raised to 110 ° C. The reaction was conducted at a pressure and a reaction temperature for 3 hours to produce sodium 3,4-dimethoxybenzoate n-butyl ester. After neutralization with hydrochloric acid, the 1-butanol layer was separated and distilled under reduced pressure to obtain 3,4-dimethoxybenzoic acid n-butyl ester. In the above reaction, substantially no by-product of the aromatic compound was generated. Table 1 shows the results of the reaction.

COMPARATIVE EXAMPLE 1 The same procedure as in Example 1 was carried out except that 11.10 g of tri-n-butylamine was used without using sodium phenoxide, and 3,4-dimethoxybenzoic acid was obtained. The n-butyl ester was obtained. During this reaction,
3,4-Dimethoxybenzoic acid di-n-butylamide was by-produced. Table 1 shows the results of the reaction.

COMPARATIVE EXAMPLE 2 n-Butyl 3,4-dimethoxybenzoate was prepared in the same manner as in Example 1, except that 2.80 g of sodium carbonate was used without using sodium phenoxide. The ester was obtained. Table 1 shows the results of the reaction.

Example 2 10.85 g of 4-bromoveratrol, 6.38 g of sodium phenoxide, and 10% of Pd-C0.5 were placed in a rotary stirring type stainless steel autoclave having an internal volume of 300 ml.
3 g and 40 ml of methanol were charged, and then carbon monoxide (CO concentration: 100% by volume) was injected into the flask at a flow rate of 4 l / hr at a gauge pressure of 2 kg / cm ² , and allowed to flow through the reaction solution. While stirring the solution, the reaction temperature was raised to 100 ° C., and the mixture was reacted at the above-mentioned reaction pressure and reaction temperature for 3 hours to produce 3,4-dimethoxybenzoic acid methyl ester. After neutralization using hydrochloric acid, solvent extraction was performed using toluene, and distillation under reduced pressure was performed to obtain 3,4-dimethoxybenzoic acid methyl ester. In the above reaction, substantially no by-product of the aromatic compound was generated. Table 1 shows the results of the reaction.

Example 3 In the same manner as in Example 1 except that 4-bromoveratrol was not used, 9.35 g of p-methoxybromobenzene, and 6.22 g of calcium diphenoxide were used without using sodium phenoxide. The reaction and the operation after the reaction were performed to obtain n-butyl p-methoxybenzoate.
In the above reaction, substantially no by-product of the aromatic compound was generated. Table 1 shows the results of the reaction.

Comparative Example 3 p-Methoxybenzoic acid n-butyl ester was prepared in the same manner as in Example 3 except that 1.48 g of calcium oxide was used without using calcium diphenoxide. I got Table 1 shows the results of the reaction.

[0043]

[Table 1]

Example 4 A reaction and post-reaction operations were carried out in the same manner as in Example 1 except that 8.65 g of p-bromophenol was used without using 4-bromoveratrol, and p-hydroxybenzoic acid was used. The n-butyl ester was obtained. In the above reaction, substantially no aromatic compound was produced. The results of the reaction are shown in Table 2.

Examples 5 to 8 0.053 g of Pd black without using 10% Pd-C
(Example _{5), 5% Pd-SiO} 2 1.06g ( Example _{6), 2% Pd-Al} 2 O 3 2.65g ( Example 7) or 2% Pd-C2.65g (Example 8) The reaction and the post-reaction operations were performed in the same manner as in Example 4 except that
p-Hydroxybenzoic acid n-butyl ester was obtained.
In those reactions, substantially no aromatic by-products were formed. Table 2 shows the results of the above reactions.

Example 9 9.75 g of sodium p-bromophenoxide without using p-bromophenol and sodium phenoxide
The reaction and post-reaction operations were carried out in the same manner as in Example 4 except that only was used to obtain p-hydroxylbenzoic acid n-butyl ester. In the above reaction, substantially no by-product of the aromatic compound was generated. The results of the reaction are shown in Table 2.

[0047]

[Table 2]

Example 10 The same as Example 4 except that carbon monoxide (CO concentration; 50% by volume) diluted with nitrogen gas was used without using carbon monoxide (CO concentration; 100% by volume). The reaction and post-reaction operations were performed to obtain p-hydroxylbenzoic acid n-butyl ester. In the above reaction, substantially no by-product of the aromatic compound was generated. Table 3 shows the results of the reaction.

Example 11 A reaction and post-reaction operations were carried out in the same manner as in Example 10 except that the reaction time was changed to 8 hours instead of the reaction time of 3 hours to convert p-hydroxylbenzoic acid n-butyl ester. Obtained. In the above reaction, substantially no by-product of the aromatic compound was generated. Table 3 shows the results of the reaction.

Examples 12 to 13 The reaction and the reaction after the reaction were carried out in the same manner as in Example 10 except that sodium phenoxide was not used and 6.60 g of potassium phenoxide (Example 12) or calcium phenoxide (Example 13) was used. The operation was performed to obtain p-hydroxylbenzoic acid n-butyl ester. In the above reaction, substantially no by-product of the aromatic compound was generated.
Table 3 shows the results of the reaction.

Examples 14 to 16 Without using 1-butanol, iso-butanol 40 m
l (Example 14), 40 ml of 2-butanol (Example 1)
5) or 40 ml of benzyl alcohol (Example 16), and the reaction and post-reaction operations were carried out in the same manner as in Example 4 except that the reaction temperature was changed to the temperature shown in Table 3. -A hydroxyl benzoate was obtained. In those reactions, substantially no aromatic by-products were formed. Table 3 shows the results of the reaction.

[0052]

[Table 3]

Examples 17 to 24 Reaction and post-reaction operations were carried out in the same manner as in Example 1 except that 4-bromoveratrol was not used, and the amounts and types of aromatic bromides shown in Table 4 were used. Was performed to obtain an aromatic carboxylic acid ester corresponding to each aromatic bromide. In those reactions, substantially no aromatic by-products were formed. Table 4 shows the results of the reaction.

[0054]

[Table 4]

[0055]

According to the production method of the present invention, an aromatic bromide, an alcohol, and carbon monoxide are reacted under relatively mild reaction conditions in the presence of a palladium metal catalyst, so that by-products are not produced. Since it is substantially absent, the aromatic carboxylic acid ester can be efficiently produced in a high yield.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 69/92 C07C 69/92 201/12 201/12 205/57 205/57 205/59 205/59 227/02 227/02 229/60 229/60 // C07B 61/00 300 C07B 61/00 300 (58) Fields investigated (Int.Cl. ⁶ , DB name) C07C 69/76-69/94 C07C 67/36 C07C 201 / 12,205 / 57-205/59 C07C 227/02 C07C 229/60

Claims (1)

(57) [Claims] 1. A method comprising reacting an aromatic bromide, an alcohol, and carbon monoxide in the presence of at least one of an alkali metal salt of a phenol and an alkaline earth metal salt of a phenol, and a metal palladium catalyst. A method for producing an aromatic carboxylic acid ester.