JPH0565249A - Production of aromatic carboxylic acid ester - Google Patents

Abstract

PURPOSE:To efficiently obtain the title compound in high yield by reacting an aromatic brominated compound with carbon monoxide using a catalyst obtained by adding a palladium compound to a system consisting of an alkali metal salt of phenols and alkaline earth metal salt. CONSTITUTION:An aromatic brominated compound (e.g. 4-bromoveratrole) of formula I (R0 is alkyl or alkenyl) is reacted with an alcohol of formula III (R' is alkyl, cycloalkyl, etc.) and carbon monoxide in the presence of a catalyst obtained by combining an alkali metal salt or alkaline earth metal salt (especially preferably Na salt, Ca salt) of phenols such as phenol, o-cresol, p-bromophenol, o-hydroxybenzoic acid ester with palladium compound (e.g. benzonitrile complex of palladium acetate or palladium chloride, palladium acetylacetonate) to provide the aromatic carboxylic acid ester (e.g. 3, 4- dimethoxybenzoic acid n-butyl ester) of formula IV (R1 is alkyl, alkenyl, aryl, etc.).

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel method for producing an aromatic carboxylic acid ester. Aromatic carboxylic acid esters have an extremely wide range of applications such as pharmaceuticals, agricultural chemicals, dye / pigment intermediates, polymer raw materials, plasticizers and preservatives.

[0002]

2. Description of the Related Art Conventional methods for producing aromatic carboxylic acid esters include, for example, aromatic carboxylic acids or their derivatives (carboxylic acid salts, acid halides or acid anhydrides), alcohols or their derivatives. Is generally used to produce an esterified product.

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 is a raw material in the above-mentioned general production method. However, there is a problem that an aromatic carboxylic acid having a high-purity substituent may not be freely obtained.

Further, as another method for producing an aromatic carboxylic acid ester, the presence of a palladium-based catalyst, a nickel-based catalyst, etc., of an aromatic halide (iodide, chloride and bromide), an alcohol and carbon monoxide is used. Method of synthesis under high temperature and high pressure (J. Org. Chem. 39
(No. 23) 3318 (1974), Bull. Ch
em. Soc. Jpn. 48 (No. 7) 2075 (1
975)) and the like are known.

However, this known production method has problems that the reaction yield is low, the selectivity is low, the expensive catalyst component is difficult to recover, and a toxic compound is produced from the catalyst component. , Was not necessarily industrially satisfactory. *

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

[0007]

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

[0008]

According to the present invention, an aromatic bromide, an alcohol and carbon monoxide are mixed with at least one of alkali metal salts and alkaline earth metal salts of phenols (second component), and palladium. The present invention relates to a method for producing an aromatic carboxylic acid ester, which comprises reacting in the presence of a compound catalyst (first component).

The production method of the present invention generally uses a reaction carried out according to the following reaction formula I. An aromatic bromide, alcohol and carbon monoxide are reacted in the presence of at least one of alkali metal salts and alkaline earth metal salts of phenols and a catalyst of a palladium compound to synthesize an aromatic carboxylic acid ester. If necessary, after completion of the reaction, the compound IV can be neutralized to form an aromatic carboxylic acid ester having a hydroxyl group or the like.

[0010]

[Chemical 1]

In the above formula, R ₀ is an alkyl group, an alkenyl group, an aryl group, a cycloalkyl group, an alkoxy group,
From the group consisting of 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, chlorine atom and bromine atom. 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 atom and atom selected from the group consisting of alkaline earth metal salts, chlorine atom and (-COOR ') group {corresponding to R'of alcohol (R'OH) (II) in each reaction formula} Represents a group.

In the above formula, R'in R'OH (III) is methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, 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. ..

Reaction formula II below shows the case where R ₂ is an aromatic bromide (I ₁ ) other than bromine, a carboxyl group or a hydroxyl group which is an “inert substituent for this reaction” as a reaction raw material. Is a reaction formula of.

[0015]

[Chemical 2]

In the following reaction formula III, R ₂ in the reaction formula II becomes 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 when an aromatic bromide (I ₂ ) of 1 to 4 is used as a reaction raw material. In this case, even if the alkali metal salt and alkaline earth metal salt of phenols are not added as the second component, the above aromatic bromide also acts as the alkali metal salt and alkaline earth metal salt of phenols, and therefore the reaction Aromatic carboxylic acid ester (I
V ₂ ) can be produced and, if necessary, neutralization can be carried out after the reaction is completed to give compound IV ₂ as an aromatic carboxylic acid ester having a hydroxyl group.

[0017]

[Chemical 3]

The following reaction formula IV corresponds to R in the reaction formula I.
Aromatic bromide in which ₀ is a hydroxy group (-OH) (I
It is a reaction formula when ₃ ) is used as a reaction raw material. Aromatic carboxylic acid ester (IV ₃ ) can be produced, and if necessary, neutralization is carried out after completion of the reaction to give compound I
V ₃ can also be an aromatic carboxylic acid ester having a hydroxyl group.

[0019]

[Chemical 4]

Examples of the aromatic bromide used in the production method of the present invention include bromobenzene, o-bromotoluene, m-bromotoluene, p-bromotoluene and p-bromotoluene.
-Bromostyrene, 4-bromobiphenyl, o-methoxybromobenzene, m-methoxybromobenzene, p-
Methoxybromobenzene, 2,4-dimethoxybromobenzene, 2,5-dimethoxybromobenzene, 4-bromoveratrol, p-phenoxybromobenzene, m-
Bromoacetophenone, p-bromophenyl acetate, p-
Nitrobromobenzene, m-cyanobromobenzene, p
-Bromobenzaldehyde, p-bromoaniline, p-
Methyl bromobenzoate, p-bromobenzoic acid, p-dibromobenzene, p-chlorobromobenzene, 4-bromosalicylaldehyde, 4-bromo-5-nitroveratrol, 4-bromo-5-methylveratrol and the like. An aromatic bromide having a reaction-inert group (R ₂ ), o
-Bromophenol, m-bromophenol, p-bromophenol, 4-bromocatechol, 4-bromoresorcin, 2-bromohydroquinone, 5-bromoguaiacol, 4-bromoguaiacol, etc., aromatic bromide having a hydroxyl group, sodium Aromatic bromide having a substituent of alkali metal salt of hydroxyl group such as p-bromophenoxide, o-dibromobenzene, p-
Dibromobenzene, m-dibromobenzene, 4,4'-
Suitable examples include aromatic bromides having a plurality of bromine atoms such as dibromobiphenyl.

When an aromatic chlorinated compound having no bromine atom is used, no aromatic carboxylic acid ester is produced 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, for example, methanol, ethanol, 1-propanol, 2- Propanol, 1-butanol, 2-butanol, iso-butanol, t-butanol, 1-pentanol, 2-pentanol, 1-
Hexanol, 2-hexanol, 1-octanol,
2-ethylhexanol, cyclopentanol, cyclohexanol, allyl alcohol, crotyl alcohol, benzyl alcohol, 2-phenylethanol, cinnamyl alcohol, etc. can be mentioned. In particular, aliphatic primary or secondary alcohols having 1 to 6 carbon atoms are preferable.

In the production method of the present invention, alcohol can also be used as a reaction solvent, and the amount used is
It may be an amount sufficient to dissolve the aromatic bromine compound, and may be an excess amount with respect to the aromatic bromide, but in the present invention, it is 0.
It is preferable to use the alcohol in an amount of about 5 to 20 mol times.

As the carbon monoxide used in the production method of the present invention, high-purity carbon monoxide may be used.
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 of the reaction system (reaction pressure) is 10 kg / cm ² or less, but it is preferable that the pressure is about normal pressure. If the reaction pressure becomes too high,
This is not preferable because the reactivity is lowered and the yield of the desired product is remarkably lowered.

The catalyst of the palladium compound used in the production method of the present invention is (a) a palladium salt or oxide; for example, palladium acetate, palladium nitrate, palladium chloride, palladium bromide, palladium iodide, sodium palladium chloride, Palladium oxide etc. can be mentioned. (B) Pd (OAc) ₂ (CH ₃ ) which is a complex with a palladium salt or the like; for example, a palladium salt or the like, a complex with an organic ligand such as acetonitrile, benzonitrile, acetylacetone, or 1,5-cyclooctadiene. CN)
₂ , PdCl ₂ (PhCN) ₂ , Pd (acac) ₂ ,
And the like PdCl ₂ (1,5-cyclooctadiene).

When the above palladium salt complex is used as a palladium catalyst, the catalyst may be added directly to the reaction solution, but the palladium salt and the organic ligand are separately added to the reaction solution, The complex may be formed in the reaction solution.

The amount of the palladium compound used is preferably 0.01 to 10% by weight, more preferably 0.05 to 5% by weight, relative to the aromatic bromide.

Examples of alkali metal salts or alkaline earth metal salts of phenols used in the production method of the present invention include phenol, o-cresol, m-cresol,
sodium salt, potassium salt, cesium salt, magnesium salt, calcium salt of p-cresol, o-bromophenol, p-bromophenol, o-hydroxylbenzoic acid ester, p-hydroxylbenzoic acid ester and the like,
Examples thereof include alkali metal salts such as barium salts and alkaline earth metal salts. Particularly, potassium salt, sodium salt, calcium salt and the like are preferable.

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

When a hydroxyl group-substituted aromatic bromide is used as the aromatic bromide used in the production method of the present invention, the corresponding hydroxyl group-substituted aromatic bromide alkali metal salt or alkaline earth metal salt is used. As a result, the number of unreacted substances in the reaction solution is small, so that the reaction products can be easily separated.

The amount of the above-mentioned salt of phenols used is 0.1 to 10 mole times, particularly 0.3 to 5 mole times per mole of the aromatic bromide. Is preferred.

In the production method of the present invention, the reaction solvent is
As mentioned above, alcohol can be used as a reaction solvent, and it is not necessary to use other solvent, but if necessary, ether type ether such as diethyl ether, diethylene glycol diethyl ether, tetrahydrofuran, 1,4-dioxane, etc. Solvents, aromatic hydrocarbon solvents such as benzene, toluene, xylene, nitrobenzene, 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 production method of the present invention, the reaction temperature is preferably 5 to 250 ° C, particularly preferably 50 to 200 ° C. In the production method of the present invention, in particular, reaction temperature: normal temperature to 150 ° C. and reaction pressure: 0.1 to 5 kg / cm
^The reaction can be carried out sufficiently even under mild conditions such as ^{2 and} the production of by-products is substantially absent, so that the target compound can be easily produced industrially.

After completion of the reaction, the compound of the present invention is easily separated from the reaction solution by a general method such as neutralization with a mineral acid salt such as hydrochloric acid, solvent extraction if necessary, and vacuum distillation.・ Can be purified.

[0036]

EXAMPLES Next, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples unless it exceeds the gist thereof.

Example 1 4-bromoveratrol 10.85 g, sodium phenoxide 6.38 g, and palladium acetate 0.112 were placed in a 100 ml glass flask equipped with a gas inlet tube and a cooling tube.
g and 1-butanol 40 ml were charged, the reaction pressure was kept under normal pressure (1 kg / cm ² ), and then carbon monoxide (CO
(Concentration: 100% by volume) at a flow rate of 4 l / hr to flow in the reaction solution, and the reaction solution is stirred, and the reaction temperature is raised to 110 ° C. And reacted for 3 hours at the reaction temperature to generate 3,4-dimethoxybenzoic acid n-butyl ester. After neutralizing with hydrochloric acid, the 1-butanol layer was separated and distilled under reduced pressure to obtain 3,4-dimethoxybenzoic acid n-butyl ester. Substantially no aromatic by-products were formed in the above reaction. The results of the above reaction are shown in Table 1.

Comparative Example 1 3,4-Dimethoxybenzoic acid was obtained by the same reaction and after-reaction procedure as in Example 1 except that sodium phenoxide was not used and 11.10 g of tri-n-butylamine was used. Obtained n-butyl ester. During this reaction,
3,4-Dimethoxybenzoic acid di-n-butylamide was by-produced. The results of the above reaction are shown in Table 1.

Comparative Example 2 n-Butyl 3,4-dimethoxybenzoate was prepared in the same manner as in Example 1 except that sodium phenoxide was not used and 2.80 g of sodium carbonate was used. The ester was obtained. The results of the above reaction are shown in Table 1.

Example 2 In a rotary stirring type stainless steel autoclave having an inner volume of 300 ml, 10.85 g of 4-bromoveratrol, 6.38 g of sodium phenoxide and 0.1 of palladium acetate were placed.
12 g and 40 ml of methanol were charged, and then carbon monoxide (CO concentration: 100% by volume) was pressed into the flask at a gauge pressure of 2 kg / cm ² at a flow rate of 4 l / hr to circulate in the reaction solution to carry out the reaction. While stirring the liquid, the reaction temperature was raised to 100 ° C., and the reaction was carried out at the reaction pressure and the reaction temperature for 3 hours to generate 3,4-dimethoxybenzoic acid methyl ester. After neutralization using hydrochloric acid, solvent extraction was performed using toluene, and distillation was performed under reduced pressure to obtain 3,4-dimethoxybenzoic acid methyl ester. Substantially no aromatic by-products were formed in the above reaction. The results of the above reaction are shown in Table 1.

Example 3 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 P-methoxybenzoic acid n-butyl ester.
Substantially no aromatic by-products were formed in the above reaction. The results of the above reaction are shown in Table 1.

Comparative Example 3 P-methoxybenzoic acid n-butyl ester was prepared by the same reaction as in Example 3 except that calcium diphenoxide was not used and 1.48 g of calcium oxide was used. Got The results of the above reaction are shown in Table 1.

[0043]

[Table 1]

Example 4 Without using 4-bromoveratrol, 8.65 g of p-bromophenol was used, and -OM in the produced compound was -OH.
The reaction and post-reaction operations were carried out in the same manner as in Example 1 except that the reaction mixture was neutralized to a sufficient change to give p-hydroxylbenzoic acid n-butyl ester. Substantially no aromatic compound was produced in the above reaction. The results of the above reaction are shown in Table 2.

Examples 5-8 Palladium chloride 0.089 without palladium acetate
g (Example 5), 0.115 g of palladium nitrate (Example 6), and benzonitrile complex PdCl _{2 of} palladium chloride.
(PhCN) ₂ 0.192 g (Example 7) or palladium acetylacetonate Pd (acac) ₂ 0.152
g (Example 8) was used, and the reaction and the operation after the reaction were performed in the same manner as in Example 4 to obtain p-hydroxylbenzoic acid n.
-Butyl ester was obtained. Substantially no aromatic by-products were formed in those reactions. The results of each reaction are shown in Table 2.

Example 9 p-Hydroxybenzoic acid n-butyl ester was obtained by the same procedure as in Example 4 except that sodium phenoxide was not used and 7.27 g of potassium phenoxide was used. Obtained. Substantially no aromatic by-products were formed in the above reaction. The results of the above reaction are shown in Table 2.

Example 10 Sodium-p-bromophenoxide 9.75 without using p-bromophenol and sodium phenoxide
The reaction and the operation after the reaction were performed in the same manner as in Example 4 except that only g was used to obtain p-hydroxylbenzoic acid n-butyl ester. Substantially no aromatic by-products were formed in the above reaction. The results of the above reaction are shown in Table 2.

[0048]

[Table 2]

Example 11 The reaction and the reaction after the reaction were carried out in the same manner as in Example 4 except that the reaction time was changed to 8 hours instead of 3 hours to give p-hydroxylbenzoic acid n-butyl ester. Obtained. Substantially no aromatic by-products were formed in the above reaction. The results of the above reaction are shown in Table 3.

Examples 12 to 14 Iso-butanol (Example 12), 2-butanol (Example 13) or benzyl alcohol (Example 14) was used without using 1-butanol, and the reaction temperature was as shown in Table 3. Except that the temperature indicated by 1 was used, the reaction and the operation after the reaction were performed in the same manner as in Example 4 to obtain p values corresponding to the respective alcohols.
-Hydroxyl benzoate was obtained. Substantially no aromatic by-products were formed in those reactions. The results of the above reaction are shown in Table 3.

[0051]

[Table 3]

Examples 15 to 19 The reaction and the operation after the reaction were performed in the same manner as in Example 1 except that 4-bromoveratrol was not used and the amount and kind of aromatic bromide shown in Table 4 was used. Was carried out to obtain an aromatic carboxylic acid ester corresponding to each aromatic bromide. Substantially no aromatic by-products were formed in those reactions. The results of the above reaction are shown in Table 4.

[0053]

[Table 4]

[0054]

INDUSTRIAL APPLICABILITY According to the production method of the present invention, an aromatic bromide, an alcohol, and carbon monoxide are reacted in the presence of a catalyst of a palladium compound under relatively mild reaction conditions to produce a by-product. Since it is substantially absent, the aromatic carboxylic acid ester can be efficiently produced in a high yield.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location C07C 67/36 201/12 205/57 6917-4H 227/02 229/54 8930-4H // C07B 61/00 300

Claims (1)

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