JPS60248647A - Production of alpha-phenylethylamine - Google Patents

Abstract

PURPOSE:To obtain alpha-phenylethylamine, economically, in high yield and purity, by the catalytic reduction of acetophenone in the presence of hydrogen, ammonia, a solvent and hydrated alumina, using a hydrogenation catalyst. CONSTITUTION:The objective compound can be produced by the catalytic reduction of acetophenone in the presence of a hydrogenation catalyst (e.g. nickel, cobalt, palladium, etc.), hydrogen, ammonia, and a solvent (e.g. methanol, dioxane, etc.), and in the presence of a hydrated alumina [e.g. Al(OH)3, Al2O3.3H2O, etc.) at 50-150 deg.C, preferably 70-130 deg.C, under a hydrogen pressure of 2kg/cm<2>- 100kg/cm<2>. The amount of the hydrated alumina is preferably 1-10pts.wt. per 1pt.wt. of the catalytic metal, and that of the ammonia is 1-20mol per 1mol of acetophenone.

Description

[Detailed description of the invention] Regarding.

The reaction of synthesizing α-phenylethylamine from acetophenone in the presence of hydrogen, ammonia and a solvent using a hydrogenation catalyst is well known, and a nickel catalyst, particularly Raney nickel, is generally used as the hydrogenation catalyst.

For example,
(Georg Thieme Verlag 1 9
5 7th edition) Vol. 11 No. 1, 6t2 was heated under hydrogen pressure of 100 to 1 in the presence of methanol as a solvent and a small amount of acetic acid.
A method of reacting at 50 atm and 130°-150°C is described, and it is said that the desired product can be obtained with a yield of 91%. It is assumed that the acetic acid added in this case has the effect of promoting the O formation of l-phenylethanimine, a condensation product of acetophenone and ammonia, which is an intermediate in the reaction, and the reaction in the absence of acetic acid or other acidic substances. In this case, the by-product rate of α-phenylethyl alcohol, which is a reduction product of acetophenone itself, increases, and the yield of the target product decreases.

Therefore, there are methods for efficiently and economically separating this by-produced α-phenylethyl alcohol from the target product (e.g., JP-A-55-2630), and methods using catalysts with good selectivity (e.g., JP-A-54-1999). 132534), special reaction methods that improve the selectivity of the reaction (for example, JP-A-54-1
03804), etc. have been proposed, but they have drawbacks such as complicated operations.

Therefore, the inventor of the present invention earnestly searched for a method that does not have these drawbacks, and as a result, arrived at the present invention.

That is, the purpose of the present invention is to produce α-phenylethylamine from acetophenone by allowing alumina hydrate to coexist in the reaction system, thereby producing the desired product much more economically than with conventional methods. The purpose is to provide a way to obtain

According to the method of the present invention, substantially all of the charged acetophenone can be reacted and the target product can be obtained with a high selectivity of 95% or more. By separating ethyl alcohol as a bottom residue, it is possible to obtain highly pure α-phenylethylamine in high yield.

The catalyst used in the present invention may be any commonly used hydrogenation catalyst, such as nickel, cobalt, orradium, but nickel catalysts are particularly preferred. The amount of catalyst to be used can be set arbitrarily, but it is preferably in the range of 1% to 50% of the weight of acetophenone as the catalyst metal.

Alumina hydrate is ru(OH)3 or Al2O,・3
H20 is generally produced, and various methods for producing it are known, but any one produced by the above chemical formula can be effectively used. There is no particular restriction on the amount used, but if it is too small, the effect will decrease, and if it is too large, it will limit the size of the reaction vessel and affect other economic efficiency. A range of 10 times the amount is preferred. In order to make alumina hydrate coexist in the reaction system, methods such as simply adding the necessary amount of alumina hydrate to the reaction system or using alumina hydrate supporting a catalyst metal are taken.

Theoretically, the amount of ammonia to be used should be at least equimolar to the amount of acetophenone, but good results cannot be obtained even if it is used in too large a quantity, so it is 1 to 20 times the amount of acetophenone. Preferably selected within the range.

The hydrogen pressure may be 1 ki/cr71 or less as a hydrogen partial pressure, but 2 Jt9/cit to 100I &/
- is preferred.

The reaction temperature is preferably from 50°C to 150°C, preferably from 70°C to 130'C.

Since water is produced as a result of the reaction, the solvent is preferably a substance that can be mixed well with water, acetophenone, and the reaction product α-phenylethylamine. Usually, alcohols such as methanol, ethers such as dioxane, and tetrahydrofuran are used. Preferred choice.

EXAMPLES The method of the present invention will be specifically explained below using Examples, but the present invention is not limited by the Examples.

Example 1 Acetophenone 30F (0.25 mol), liquid ammonia 12.8F (0.75 mol), and methanol 60? were placed in a stainless steel autoclave with an internal volume of 20ON. ,
Prepare alumina hydrate 18v1 Raney Nickel 62,
After the air inside the vessel was diluted with hydrogen gas, hydrogen gas was pressurized at 26℃ to make the total pressure 30kf//crli, and
After raising the temperature to 00°C, the reaction was carried out by stirring for 400 minutes.

Analysis of the reaction solution by gas chromatography revealed that the conversion rate of acetophenone was 98.9% and the selectivity to α-phenylethylamine was 99.3%.

Example 2 Acetophenone 15 F (0,125 mol) was placed in a stainless steel autoclave with an internal volume of 200 WLl.
A catalyst containing nickel 32 obtained by supporting 12.8 f (0.75 mol) of liquid ammonia, 402 methanol, and nickel chloride on alumina aqueous phase 15F and reducing it with sodium borohydride was charged. After replacing the inside of the vessel with hydrogen gas, pressurize hydrogen gas at 22℃ to bring the total pressure to 20#.
/cr! The reaction was carried out by raising the temperature to 85°C and stirring for 440 minutes. As a result of analyzing the reaction solution by gas chromatography, the conversion rate of acetophenone was 97%, α-
The selectivity to phenylethylamine was 96.1%, and α
- The by-product rate of phenylethyl alcohol was 3.9%.

Example 3 Acetophenone 45F (0,375 mol), liquid ammonia 9.5F (0,56 mol), ethanol 702,
It was prepared from Raney alloy 10v. After charging the catalyst containing alumina hydrate and purging the inside of the vessel with hydrogen gas,
Hydrogen gas was pressurized at 110° C. to bring the total pressure to 40 kf//cr/I, and the reaction was carried out by stirring at 110° C. for 360 minutes.

Analysis of the reaction solution by gas chromatography revealed that the conversion rate of acetophenone was 99.6% and the selectivity to α-phenylethylamine was 98.8%.

Patent applicant Yamakawa Pharmaceutical Co., Ltd.

Claims (1)

[Claims] α-phenyl is characterized in that when acetophenone is catalytically reduced in the presence of a hydrogenation catalyst, hydrogen, ammonia and a solvent to produce α-phenylethylamine, the catalytic reduction is carried out in the presence of alumina hydrate. Method for producing ethylamine.