JPH0414094B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention uses aromatic iodides, carbon monoxide, aliphatic alcohols, and aliphatic tertiary amines to produce aromatic
The present invention relates to a method for producing an α-ketocarboxylic acid ester. Aromatic α-ketocarboxylic acid esters can be easily derived into aromatic α-amino acids and are important compounds as raw materials for pharmaceuticals, food additives, feed additives, surfactants, and the like. It has been known that aromatic carboxylic acid esters are produced by reacting aromatic halides, carbon monoxide, aliphatic alcohols, and bases at normal pressure in the presence of a palladium catalyst. It was not known to produce -α-ketocarboxylic acid esters. The present inventor has discovered that aromatic halides, carbon monoxide,
As a result of extensive research into a method for producing aromatic-α-ketocarboxylic acid esters from raw materials consisting of aliphatic alcohols and bases, we found that by using an aliphatic tertiary amine as a base and reacting under pressure with carbon monoxide, It has been found that aromatic-α-ketocarboxylic acid esters can be obtained with high selectivity. That is, the present invention produces aromatic -α The present invention relates to a method for producing -ketocarboxylic acid esters with high selectivity. The reaction of the present invention proceeds according to the following formula. Ar-I+2CO+ROH+NR' ₃ →ArCOCOOR+NR' ₃・HI (Ar: aryl group, R and R': alkyl group) The aromatic iodide used in the method of the present invention has the general formula: (X: represents a hydrogen atom, a _C1-5 alkyl group, a _C1-5 alkoxy group, a chlorine atom, or a bromine atom, respectively). The aliphatic alcohol preferably has 2 to 16 carbon atoms. Examples include ethyl alcohol, propyl alcohol, butyl alcohol, aluminum alcohol, and decyl alcohol. Examples of aliphatic tertiary amines include trimethylamine, triethylamine, tripropylamine,
Examples include tributylamine, methyldiethyleneamine, and trioctylamine. In this reaction, aromatic iodide, aliphatic alcohol, and aliphatic tertiary amine react in equimolar ratios, respectively, according to the above reaction formula. The amount used can be varied in molar ratio between 0.1 and 10, respectively. Carbon monoxide is preferably used in an excess amount, for example, preferably at a pressure of 0.5 Kg/cm ² G or more, particularly preferably 10 Kg/cm ² G or more. Bis(triphenylphosphine)dichloropalladium, bis(triphenylphosphine)diiodopalladium, bis(triphenylphosphine)dibromopalladium as bis(triphenylphosphine)palladium halide complexes used in the method of the present invention , halogenated palladium bis(triphenylphosphine) complexes such as bis(triphenylphosphine)iodophenylpalladium, and the like. The appropriate amount of the bis(triphenylphosphine) halogenated palladium complex to be used is 0.0001 to 0.1 Pd-g atoms per mole of aromatic iodide. Further, it is not necessary to use a particular solvent, but when a solvent is used, aromatic hydrocarbons such as benzene and toluene, or ethers such as dioxane are mentioned. The reaction temperature is preferably 10 to 200°C, particularly 50 to 100°C. The target product obtained by carrying out the method of the present invention is an aromatic-α-ketocarboxylic acid ester corresponding to the aromatic iodide represented by the above general formula, such as phenylglyoxylate, alkoxy Examples include phenylglyoxylate, alkyl phenylglyoxylate, and halogenated phenylcrioxylate. In addition to the target product, aromatic carboxylic acid ester is also produced as a by-product in this reaction, but aromatic iodide,
A method for obtaining aromatic-α-ketocarboxylic acid esters with high selectivity from carbon monoxide, aliphatic alcohols and aliphatic tertiary amines is based on a novel reaction. Example 1 20 mmol (4.08 g) of benzene iodide, 46.1 mmol (5 ml) of isoamyl alcohol, 20 ml of triethylamine, and 0.2 mmol of dichlorobis(triphenylphosphine) palladium (PPh ₃ ) ₂ PdCl ₂ were placed in a glass tube autoclave.
Carbon monoxide was injected at 120 kg/cm ² G. The autoclave was heated to 60°C and shaken for 24 hours. After cooling to room temperature, remove the reaction solution from the autoclave.
Respective fractions of benzene iodide, isoamyl phenylglyoxylate, and isoamyl benzoate were obtained by vacuum distillation. A certain amount of it was analyzed by gas chromatography. As a result, the remaining amount of iodized benzene was 5.32 mmol (conversion rate 73.4%),
Production amount of isoamyl phenylglyoxylate 11.4 mmol (selectivity 77.7% based on benzene iodide),
Isoamyl benzoate is 2.86 mmol (selectivity 19.5% based on benzene iodide), and the molar ratio of ketoacid ester to ester (KE/E.) of the product is 3.99.
It was hot. The products, isoamyl phenylglyoxylate and isoamyl benzoate, were identified by distilling the reaction solution under reduced pressure, separating the resulting fraction using gas chromatography, and performing elemental analysis and infrared absorption spectrum and NMR absorption with the standard. This was done by comparing with the spectrum. Examples 2 to 5 Using 20 mmol of aromatic iodide, 5 ml of isoamyl alcohol (Ph ₃ P) ₂ 0.1 mmol of PdCl ₂ and 20 ml of triethylamine were charged into an autoclave, carbon monoxide 50 Kg/cm ² G, reaction temperature 80°C. The reaction was carried out for 5 hours. The results are shown in Table 1.

[Table] Examples 6 to 9 Table 2 shows the results of reactions conducted in the same manner as in Example 4 using 46.1 mmol of various aliphatic alcohols.

[Table] Example 10 A reaction was carried out in the same manner as in Example 4 except that 40 mmol of tri-n-butylamine and 0.2 mmol of (Ph ₃ P) ₂ PdCl ₂ were added instead of triethylamine. As a result, 0.8 mmol (yield 4%) of isoamyl phenylglyoxylate was obtained, and the keto acid ester/ester ratio was 0.35. Examples 11-14 Using 0.1 mmol of various bis(triphenylphosphine) halogenated palladium complexes shown in Table 3 and 20 mmol of isoamyl alcohol,
Table 3 shows the results of the reaction conducted in the same manner as in Example 4.

[Table] Example 15 The reaction was carried out in the same manner as in Example 4 except that 0.1 mmol of bis(triphenylphosphine)dichloropalladium was added. As a result, the conversion rate of iodobenzene was 7%, and the yield of phenylglyoxylate was 7%. The ratio is 2.9% and the molar ratio of ketoester/ester is
It was 2.71. Comparative Examples 1 to 5 Table 4 shows the results of a reaction conducted in the same manner as in Example 4 using 0.1 mmol of the various palladium compounds shown in Table 4 and 20 mmol of isoaluminum alcohol.

[Table] Comparative Example 6 The same procedure as in Example 4 was carried out except that 20 mmol of chlorobenzene was used. As a result, phenylglyoxylic acid ester could not be detected. Example 16 and Comparative Example 7 40 mmol of the base shown in Table 5 was used, 20 mmol of benzene iodide, and 5 mmol of isoamyl alcohol.
ml (Ph ₃ P) ₂ PdCl ₂ 0.2 mmol and benzene 100 ml were placed in an autoclave, carbon monoxide, 100 kg/
The same procedure as in Example 4 was carried out, except that the reaction was carried out at cm ² G and reaction temperature of 80° C. for 5 hours. The results are shown in Table 5.

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Claims (1)

[Claims] 1. General formula: (In the formula, X is a hydrogen atom, a C1 to C5 alkyl group,
Aromatic iodides, carbon monoxide, aliphatic alcohols, and aliphatic tertiary amines represented by C1 to C5 alkoxy groups, chlorine atoms, or bromine atoms, respectively, are converted into bis(triphenylphosphine) halogenated compounds. A method for producing an aromatic-α-ketocarboxylic acid ester, which comprises performing a pressure reaction in the presence of a palladium complex.