JPS62904B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention involves subjecting acetophenone to a catalytic reduction reaction in the presence of ammonia and hydrogen.
Highly purified α- from the phenylethylamine reaction solution
The present invention relates to a method for separating and purifying phenylethylamine.

The method of synthesizing α-phenylethylamine by condensing and hydrogenating acetophenone with ammonia and hydrogen in the presence of a nickel catalyst such as Raney nickel or nickel formate has been known for a long time (East German Patent No. 42124, 49611, "Organic Synthesis"). Journal of the Chemical Society” No. 12
Vol., No. 3 (1954)), usually in methanol solvent. In the reaction, in addition to the target product, α-phenylethanol is produced as a main by-product due to the reduction of acetophenone itself. Further, depending on the reaction conditions, unreacted acetophenone may remain. Furthermore, acetophenone may contain cumyl alcohol, and when this acetophenone is used as a by-product during phenol production by the cumene method, the acetophenone contains phenol derived from the purification process, α - It also contains a small amount of methylstyrene, so it is contained in the reaction solution as is.

The usual methods for obtaining highly pure α-phenylethylamine by removing these and other impurities are to purify it by distillation using a distillation device with a high separation effect, or to add an acid to the mixture to obtain α-phenylethylamine. In this method, phenylethylamine is converted into a salt, volatile impurities are removed by steam distillation, and then an alkali is added to precipitate oily α-phenylethylamine, which is separated and distilled.

The former method is simple to operate, but for example, the boiling points of α-phenylethylamine and α-phenylethanol are 188°C and 204°C, respectively, and distillation requires a high rectification column, which is expensive to construct. On the other hand, the energy cost of steam distillation is high in the latter method.

The present inventors have discovered that, as an improvement to the latter method, the above-mentioned impurities can be easily removed by extraction with a solvent that is substantially insoluble in water instead of steam distillation, and the present invention is based on the present invention. Reached.

That is, the object of the present invention is to use a conventional method for producing α-phenylethylamine, such as a nickel catalyst,
A method for removing impurities from crude α-phenylethylamine containing impurities produced by catalytic reduction of acetophenone in the presence of ammonia and methanol, using a non-aqueous organic solvent that does not substantially dissolve water and sulfuric acid or hydrochloric acid. was added to separate the aqueous layer of α-phenylethylamine salt aqueous solution and the oil layer of non-aqueous organic solvent containing impurities contained in the reaction solution. After separating the oil layer, the aqueous layer was neutralized with alkali. α-phenylethylamine is separated as an oil layer and subjected to distillation.
- A method for separating and purifying phenylethylamine.

According to the method of the present invention, although a distillation step is included, sufficient effects can be obtained with simple distillation, so the construction cost is lower than the cost of distillation equipment with a high number of plates. Additionally, since it does not involve steam distillation, it has the advantage of low energy costs.

Nickel catalysts that can be used in the method of the present invention include Raney nickel catalysts, reduced nickel catalysts, and nickel catalysts obtained by thermally decomposing nickel formate. The amount of catalyst used is 0.1 to 15% (by weight) of acetophenone as a nickel component.
(same below) is good, but preferably 0.5 to 10%
Good.

It is desirable to use ammonia in an amount of at least 20% or more based on acetophenone, and more preferably 25% or more. There is no particular need for an upper limit, but
Better results will not be obtained using more than 100%, and usually less than 70% is sufficient.

The reaction temperature is preferably 50°C to 150°C, preferably 70°C to 120°C.

Although the pressure of the reaction system depends on the temperature, it is usually 2 to 150 kg/cm ² , preferably 5 kg/cm ² to 130 kg/cm ² .

In the present invention, organic solvents that are substantially insoluble in water include benzene, toluene, xylene, ethylbenzene, cumene, α-methylstyrene, other aromatic hydrocarbons, hexane, heptane, light oil,
Examples include aliphatic hydrocarbons such as kerosene, and alicyclic hydrocarbons such as cyclohexane and decalin. These solvents may be present during the hydrogenation reaction as long as they are inert to the reaction, but if the volumetric efficiency of the reactor is taken into account, It is better to add it at an appropriate time. The amount of solvent added is based on the acetophenone used in the reaction.
3 to 400% is good, but preferably 5 to 200%
% is good.

Generally, to produce α-phenylethylamine, acetophenone, methanol, ammonia,
A catalyst and hydrogen are charged into a pressurized reactor and reacted at a predetermined temperature. After the reaction, hydrogen, ammonia,
After removing the remaining liquid and methanol and filtering off the catalyst, the residual liquid is either fractionally distilled as it is, or mineral acid is added to turn α-phenylethylamine into a salt, impurities are distilled off by steam distillation, and the mixture is neutralized with alkali. The method of the present invention is carried out during the reduction reaction, preferably after the completion of the reduction reaction, until the hydrogen, ammonia, methanol and catalyst are removed. After adding the above solvent at an appropriate time, add sulfuric acid or hydrochloric acid to α-
Form a salt of phenylethylamine, or after the completion of the reduction reaction, remove hydrogen, ammonia, methanol, and the catalyst from the reaction mass, and then add sulfuric acid or hydrochloric acid to form a salt of α-phenylethylamine. The above-mentioned organic solvent is added to the mixture, stirred thoroughly, and then allowed to stand to separate the liquids.Next, the aqueous layer is neutralized with caustic alkali, and the oil layer separated at this time is distilled. By this method, α-phenylethyl alcohol, unreacted acetophenone, cumyl alcohol that may be contained in raw materials, and other impurities can be substantially removed, resulting in highly pure α-phenylethylamine. is obtained.

α-Phenylethylamine obtained by the method of the present invention is useful as an intermediate in organic synthesis, and the optically resolved product can be widely used as an optical resolution aid for carboxylic acids having asymmetric carbon atoms. can.

Next, the method of the present invention will be explained in more detail with reference to Examples.

Example 1 Acetophenone 30g, methanol 56g,
14 g of ammonia and 3.0 g of reduced nickel catalyst (nickel content 20%) were charged, and after purging the inside of the vessel with hydrogen, the temperature was raised to 110°C. Hydrogen gas was introduced under pressure to start the reaction at a total pressure of 50Kg/ ^cm2 , and the total pressure was increased to 50Kg/cm2.
When stirring was continued at ~30 Kg/cm ² , the reaction was completed in 330 minutes. When the reaction solution was analyzed by gas chromatography, the conversion rate of acetophenone was 99.6%.
α-phenylethylamine yield 95.5%, α-phenylethanol yield 3.5%, secondary amine yield 0.5%
It was hot. Evaporate ammonia and methanol from the reaction solution, add 75 g of 20% sulfuric acid and toluene.
After adding 10 g of the mixture and stirring for 10 minutes, the mixture was allowed to stand still to separate the liquids. Add a 45% caustic soda aqueous solution to the separated aqueous layer with 28
g was added, stirred, and then separated. When the obtained oil layer of α-phenylethylamine was distilled, 24.2g
of α-phenylethylamine was recovered. As a result of gas chromatography analysis, purity is 99.38.
%, α-phenylethyl alcohol content 0.08
%, secondary amine content 0.19%, and other 0.35%.

Example 2 0.92% cumyl alcohol and phenol in a stainless steel autoclave with an internal volume of 500 ml.
1.22%, α-methylstyrene 0.63%, others 0.26
%, add 140 g of methanol, 35 g of ammonia, and 7.5 g of reduced nickel catalyst (nickel content 20%),
The mixture was stirred at 110° C. and a total pressure of 50 to 30 Kg/cm ² for 5 hours. After removing the catalyst, ammonia and methanol from the reaction mixture, 120g of ligroin was added, and the mixture was heated for 20 minutes with stirring.
% sulfuric acid was added. The liquid was separated, 69 g of 45% caustic soda was added to the aqueous layer, and the liquid was separated again to collect the oil layer. This oil layer was distilled under reduced pressure to recover 63g of a fraction at 69°C/10TORR. Analysis of this fraction by gas chromatography revealed that the purity of α-phenylethylamine was 99.28%, and the content of α-phenylethyl alcohol, cumyl alcohol, phenol, α-methylstyrene, and acetophenone was 0.16% each.
%, 0.06%, 0.18%, 0.20%, and 0.02%.
In addition, 0.10% of unknown substances were detected.

Example 3 In a stainless steel autoclave with an internal volume of 500 ml, 1.49% cumyl alcohol and phenol were added.
0.37%, α-methylstyrene 1.51%, others 4.60
% acetophenone 67.5g, methanol
140g, ammonia 35g, nickel formate thermal decomposition catalyst (nickel content 20%) 6.0g, and α-
Add 7.5g of methylstyrene, 110℃, total pressure 50~30
Kg/cm ² and stirred for 5.5 hours. 20% after removing catalyst, ammonia, and methanol from the reactant
175 g of sulfuric acid was added, and after stirring for 20 minutes, the mixture was allowed to stand to separate the oil layer. 62g of 45% caustic soda was added to the aqueous layer, stirred for 10 minutes, separated, and the oil layer was distilled under reduced pressure.
49.7 g of a fraction of °C/10 TORR. was obtained. Analysis results by gas chromatography showed that the purity of α-phenylethylamine was 99.04%, and the content of α-phenylethyl alcohol, cumyl alcohol, phenol, α-methylstyrene, and others was 0.15% and 0.04%, respectively.
%, 0.09%, 0.38% and 0.30%.

Example 4 Reduction was carried out in the same manner as in Example 2, and after removing the catalyst, ammonia and methanol from the reaction product, 120 g of ligroin was added, and 36% hydrochloric acid was added under stirring.
Add 76.6g, separate the liquids, and add 45% caustic soda to the aqueous layer.
66.7 g was added, and the layers were separated again to collect the oil layer. This oil layer was distilled under reduced pressure to obtain a distillate of 62.8 at 69℃/10TORR.
g was collected. As a result of analyzing this fraction by gas chromatography, the purity of α-phenylethylamine was 99.30%, and the contents of α-phenylethyl alcohol, cumyl alcohol, phenol, α-methylstyrene, and acetophenone were 0.16% and 0.06%, respectively.
%, 0.17%, 0.21%, and 0.02%. In addition, 0.10% of unknown substances were detected.

Comparative Example 1 Reduction was carried out in the same manner as in Example 2 to remove the catalyst, ammonia, and methanol from the reactant, followed by simple distillation under reduced pressure to obtain a fraction at 69°C/10 TORR.
69.1g was recovered. Analysis of this product by gas chromatography revealed that the purity of α-phenylethylamine was 89.55%, α-phenylethyl alcohol 3.98%, cumyl alcohol 1.12%, and phenol.
0.22%, α-methylstyrene 0.55%, others 4.58
It was %. This crude product has an outer diameter of 25 mm and a length of 40 cm.
Fractionated using a Widmer type fractionating tube, 68-69
A fraction of 60.6 g was collected at ℃/10 TORR. The results of analysis of this substance by gas chromatography are as follows:
The purity of α-phenylethylamine was 97.87%, α-phenylethyl alcohol 0.77%, cumyl alcohol 0.39%, phenol 0.18%, α-methylstyrene 0.20%, and other 0.61%.

Claims (1)

[Claims] 1. Adding a non-aqueous organic solvent that does not substantially dissolve water and sulfuric acid or hydrochloric acid to a reaction solution containing α-phenylethylamine obtained by catalytic reduction of acetophenone with ammonia and hydrogen. The mixture is separated into an aqueous layer of α-phenylethylamine salt aqueous solution and an oil layer of a non-aqueous organic solvent containing impurities contained in the reaction solution. After separating the oil layer, the aqueous layer is neutralized with an alkali. A method for separating and purifying α-phenylethylamine, which comprises separating α-phenylethylamine as an oil layer and subjecting it to distillation. 2. When producing α-phenylethylamine by catalytic reduction of acetophenone with ammonia and hydrogen, the reaction is carried out by adding in advance a non-aqueous organic solvent that does not substantially dissolve water,
Sulfuric acid or hydrochloric acid is added to the obtained reaction solution containing α-phenylethylamine to separate an aqueous layer of the α-phenylethylamine salt aqueous solution and an oil layer of the non-aqueous organic solvent containing impurities contained in the reaction solution. After separating the oil layer, the aqueous layer is neutralized with alkali and α-
A method for separating and purifying α-phenylethylamine, which comprises separating phenylethylamine as an oil layer and subjecting it to distillation.