JPH0253428B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for producing phenylpyruvic acid, and more particularly to a method for producing phenylpyruvic acid by reacting benzyl halide with carbon monoxide and water in the presence of a catalyst. Traditionally, phenylpyruvic acid has been produced by (a) benzyl halide being combined with carbon monoxide in a liquid solvent medium in the presence of a catalytic amount of a cobalt carbonyl compound and an alkaline earth metal inorganic base at a pressure of 5 to 200 bar; Method obtained by reaction (Special Publication 1986-
18587) and (b) reacting benzyl halide with carbon monoxide and an alcohol/water mixture in the presence of cobalt carbonyl and a basic compound,
At that time, a method using an alkali hydroxide as a basic compound at a reaction temperature of -10 to 70°C (Japanese Unexamined Patent Publication No. 55
-4398) is known. However, method (a) is carried out under high pressure between 5 and 200 bars, and examples show that a pressure of 40 bars or more is required to obtain phenylpyruvic acid in a practical yield. It is shown. Therefore, a pressurizing device is required for implementation. In addition, as this method requires the reaction to be carried out under increased pressure, it has been found that phenylpyruvic acid cannot be obtained in a desirable yield if the reaction is carried out under low pressure, for example, normal pressure. 56-18587). The method (b) is not limited to requiring pressure, but as is clear from the description of the examples, the yield of phenylpyruvic acid decreases as the pressure decreases, and no examples at normal pressure are described. do not have. According to the results of additional tests conducted by the present inventors under normal pressure, it was found that the desired product could not be obtained at all (see Comparative Example below). As mentioned above, both methods (a) and (b) require pressurized reaction equipment when carried out industrially, and are economically disadvantageous in various respects compared to normal pressure reaction processes. . In order to overcome the shortcomings of conventional methods, the present inventors have intensively investigated a method that can efficiently produce phenylpyruvic acid even under normal pressure without requiring investment in equipment such as pressurizing equipment. The present invention was completed based on the discovery that the objective can be achieved by using a primary alcohol or a tertiary alcohol and by specifying the amount of water used in the reaction. That is, in the present invention, in the presence of a cobalt carbonyl compound and an alkaline earth metal inorganic base, (In the formula, X represents a halogen atom), carbon monoxide, and water are reacted, and the formula In the method for producing phenylpyruvic acid represented by The present invention provides a method for producing phenylpyruvic acid, which is characterized in that the reaction is carried out under the following conditions. As the benzyl halide represented by the general formula () which is a raw material of the present invention, benzyl chloride, benzyl bromide, and benzyl iodide can be used. Carbon monoxide, which is a reaction reagent of the present invention, may be present in the amount required to carry out the reaction without being limited by pressure, but it is possible to carry out the reaction smoothly without considering a special pressurizing device. in that it can be advanced
Preferably the pressure is in the range from 0.5 to less than 5 bar. Furthermore, water, which is a reaction reagent of the present invention, is used in an amount of 7 to 40 molar equivalents relative to benzyl halide. If the amount is less than 7 molar equivalents or more than 40 molar equivalents, the yield of the desired phenylpyruvic acid tends to decrease (see Comparative Example below). It is necessary to carry out the present invention in the presence of a cobalt carbonyl compound. Examples of cobalt carbonyl compounds include dicobalt octacarbonyl,
Although hydricobalt tetracarbonyl, sodium cobalt tetracarbonylate, potassium cobalt tetracarbonylate, etc. can be used, it is preferable to use dicobalt octacarbonyl because its activity and recovery operation have been established. The amount of cobalt carbonyl compound used is selected within the range of 0.001 to 1.0 gram atom equivalent based on benzyl halide. The present invention requires that it be carried out in the presence of an alkaline earth metal inorganic base. Calcium hydroxide, calcium oxide,
Examples include barium hydroxide, strontium hydroxide, strontium oxide, magnesium hydroxide, and magnesium oxide, but calcium hydroxide is preferably used because the reaction proceeds smoothly. The amount of alkaline earth metal inorganic base used is usually 1 to 4 molar equivalents relative to benzyl halide. The present invention is carried out in a secondary alcohol or tertiary alcohol solvent having 3 to 10 carbon atoms. Secondary alcohols and tertiary alcohols having 3 to 10 carbon atoms that can be used include 2-propanol, 2-butanol, 2-
Pentanol, 3-pentanol, 3-methyl-
2-butanol, 2-hexanol, 3-hexanol, 4-methyl-2-pentanol, 3-heptanol, 2-octanol, 3-octanol, 4-octanol, 2-decanol, cyclopentanol, cyclohexanol, menthol, Borneol, 2-methyl-2-propanol, 2-methyl-2-butanol, 2-methyl-
2-pentanol, 2,3-dimethyl-2-butanol, 2-methyl-2-hexanol, 3-methyl-3-hexanol, 1-methyl-1-cyclohexanol, 1-ethyl-1-cyclohexanol, 1 -Methyl-1-octanol, 1-methyl-1-nonanol, 4-propyl-4-heptanol, etc. can be used, but since they are easily available and the reaction proceeds smoothly, 2-propanol, 2-propanol, -methyl-2-propanol or 2-
Preference is given to using methyl-2-butanol. In the present invention, the reaction is carried out under vigorous stirring. Vigorous stirring used in the present invention refers to when a reaction is carried out in a cylindrical reaction vessel without baffles using a turbine blade type stirrer having a diameter of about 2/3 of the diameter of the reaction vessel. This refers to stirring achieved at a stirrer rotation speed of approximately 500 times per minute. The reaction can be carried out at room temperature to 100°C, but is preferably 40 to 70°C in order to proceed smoothly. According to the present invention, phenylpyruvic acid can be produced by carbonylation of benzyl halide at around normal pressure of less than 5 bar, which was previously thought to be practically impossible. Therefore, the present invention is industrially extremely useful. Useful. EXAMPLES Hereinafter, the present invention will be explained in more detail using Examples in comparison with Comparative Examples. Example 1 Benzyl chloride (6.33 g, 0.05 mol) and calcium hydroxide (7.90 g, 0.11 mol), dicobalt octacarbonyl (0.85 g, 5 mol %) as catalyst,
2-methyl-2-butanol (100ml) as solvent
and water (7 ml, 0.39 mol) were introduced into a 0.3 three-necked flask equipped with a carbon monoxide inlet tube and a stirring system capable of rotating at least 1000 times per minute. (The reaction vessel is a spherical three-necked glass flask with an inner diameter of 85 mm.The stirring system uses Teflon half-moon blades, length 55 mm, and maximum width 15 mm.
Rotating diameter 55mm in mm. ) After purging the inside of the flask with carbon monoxide, it was vigorously stirred in the presence of carbon monoxide in a water bath preset at 50°C at a stirrer rotation speed of 1000 times per minute or more. After continuing to stir until the absorption of carbon monoxide was complete, the resulting reaction mixture was filtered and the solids on the reactor and filter were washed with ethanol and water. The resulting white solid was dissolved in 6N hydrochloric acid (150ml) and extracted five times with ether (50ml). The ether layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure at low temperature (below 40°C) to obtain 6.34 g of white crystals of phenylpyruvic acid.
(yield 77.2%). On the other hand, the filtrate was made acidic with concentrated salt, and then extracted five times with ethyl acetate (50 ml). The obtained organic layer was washed with a 10% aqueous sodium carbonate solution (20 ml x 5 times), dried over magnesium sulfate, and the solvent was distilled off to obtain 0.31 2-methyl-2-butyl ester of phenylacetic acid.
g (yield 3.0%) was obtained. The alkaline aqueous solution obtained from the washing operation was made acidic with concentrated hydrochloric acid and extracted with ethyl acetate (100 ml x 3). The organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure to obtain 0.82 g of white crystals of phenylacetic acid (yield:
12.0%).

[Table] Example 2 Benzyl chloride (6.33 g, 0.05 mol), calcium hydroxide (7.90 g, 0.11 mol), dicobalt octacarbonyl (0.85 g, 5 mol%) as a catalyst,
2-methyl-2-butanol (100ml) as solvent
Carbonylation was carried out using the same reaction procedure as in Example 1 using and water (20 ml, 1.11 mol). The results are shown in the table below.

【table】

[Table] Example 3 Benzyl chloride (6.33 g, 0.05 mol), calcium hydroxide (7.90 g, 0.11 mol), dicobalt octacarbonyl (0.85 g, 5 mol%) as a catalyst,
2-methyl-2-propanol (100
ml) and water (9 ml, 0.5 mol), carbonylation was carried out in the same manner as in Example 1. The results are shown in the table below.

[Table] Example 4 Benzyl chloride (6.33 g, 0.05 mol), calcium hydroxide (7.90 g, 0.11 mol), dicobalt octacarbonyl (0.85 g, 5 mol%) as a catalyst,
2-methyl-2-propanol (100
ml) and water (30 ml, 1.67 mol), the same reaction procedure as in Example 1 was carried out to carry out carbonylation. The results are shown in the table below.

[Table] Example 5 Benzyl chloride (6.33 g, 0.05 mol) and calcium hydroxide (7.41 g, 0.1 mol), dicobalt octacarbonyl (0.85 g, 5 mol %) as a catalyst, 2-methyl-2- as a solvent Butanol (100ml)
and water (20 ml, 1.11 mol) were introduced into a 0.2 stainless steel autoclave equipped with a stirring system capable of over 1300 revolutions each time. (The inner diameter of the reaction vessel is 41 mm.
mm, internal height 156mm. The stirring system is a turbine blade type, and the size of the blades (4 blades) is 13 mm in height and 7 mm in width.
mm and the rotation diameter is 28mm. ) After purging the inside of the autoclave with carbon monoxide, it was vigorously stirred (1300 rpm) at 60° C. for 2 hours under a constant pressure of carbon monoxide of 4 bar.
After the reaction was complete, the autoclave was degassed, the reaction mixture was filtered while hot, and the solids on the reactor and filter were washed with ethanol and water. The resulting white solid was dissolved in 6N hydrochloric acid (150ml) and extracted five times with ether (50ml). The ether layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure at low temperature (below 40°C) to obtain 6.55 g of white crystals of phenylpyruvic acid (yield 79.8%).
I got it. On the other hand, the filtrate was completely distilled to remove the solvent under reduced pressure, and 6N hydrochloric acid (50 ml) was also added to the obtained solid.
Extracted three times with ether (50ml). The ether layer was dried over magnesium sulfate and the ether was distilled off under reduced pressure to obtain a white solid of phenylacetic acid.
0.75g (yield 11.0%) was obtained. The results are shown in the table below.

[Table] Example 6 A carbonylation reaction was carried out in the same manner as in Example 5 except that the reaction time was 5 hours. The results are shown in the table below.

[Table] Example 7 A carbonylation reaction was carried out in exactly the same manner as in Example 5 except that 2-propanol was used as the reaction solvent. The results are shown in the table below.

[Table] Example 8 A carbonylation reaction was carried out in exactly the same manner as in Example 7, except that the rotation speed of the stirrer was changed to 500 revolutions per minute.
The results are shown in the table below.

[Table] Comparative Examples 1 to 3 Study on the amount of water used Using dicobalt octacarbonyl (0.85 g, 5 mol%) as a catalyst, under 1 atmosphere of carbon monoxide pressure, 2
- Methyl-2-butanol was used as the solvent, water 1
Benzyl chloride (6.33 g, 0.05 mol) was prepared in the same manner as in Example 1 using 2 ml (0.11 mol) of water (Example 2) and 50 ml (2.78 mol) of water (Example 3). Carbonylation was carried out. The results are shown in the table below.

[Table] Comparative Example 4 Benzyl chloride (6.00 g, 0.047 mol) and dicobalt octacarbonyl (0.18 g, 1.1 mol) as a catalyst
mol %) and 2-methyl-2-propanol (13.8 ml) as a solvent were introduced into a 0.3 mm three-necked flask equipped with a carbon monoxide inlet tube and a stirring system.
After replacing the inside of the flask with carbon monoxide, the temperature is 32-33℃.
26.4 g of a 9.7% by weight aqueous solution of lithium hydroxide was slowly added dropwise over 3 hours using a syringe pump while stirring vigorously in the presence of carbon monoxide in a water bath set at . After the addition was completed, the mixture was further stirred for 1 hour, and the resulting reaction mixture was treated in the same manner as in Example 1. The results are shown in the table below.

[Table] Comparative Example 5 A carbonylation reaction was carried out in exactly the same manner as in Example 5, except that the stirrer rotation speed was 300 revolutions per minute.
The results are shown in the table below.

【table】

Claims (1)

[Claims] 1. In the presence of a cobalt carbonyl compound and an alkaline earth metal inorganic base, the general formula (In the formula, X represents a halogen atom), carbon monoxide, and water are reacted, and the formula In the method of producing phenylpyruvic acid represented by The method for producing phenylpyruvic acid, characterized by carrying out the reaction with. 2. Process according to claim 1, characterized in that the reaction is carried out under a carbon monoxide pressure of less than 5 bar. 3. The method according to claim 1 or 2, wherein the cobalt carbonyl compound is dicobalt octacarbonyl. 4. The method according to any one of claims 1 to 3, wherein the alkaline earth metal inorganic base is calcium hydroxide. 5 Secondary alcohol or tertiary alcohol is 2
-propanol, 2-methyl-2-propanol or 2-methyl-2-butanol. 6. Process according to any one of claims 2 to 5, characterized in that the reaction is carried out under a carbon monoxide pressure of 0.5 bar or more. 7. The method according to any one of claims 1 to 6, wherein the reaction is carried out at a temperature of room temperature to 100°C. 8. Vigorous stirring is achieved at a stirring speed of about 500 revolutions per minute when the reaction is carried out using a turbine blade type stirrer having a diameter of about 2/3 of the diameter of the reaction vessel. A method according to any one of claims 1 to 7.