JP2002255907A - Method for producing 3-arylpropylamine - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for easily producing a 3-arylpropylamine expressed by general formula (2): R-CH2 CH2 CH2 NH2 ...(2) (R is an aryl) in high yield. SOLUTION: A 3-arylpropylamine expressed by general formula (2) is produced by reacting an arylacrolein expressed by general formula (1): R-CH=CH- CHO...(1) (R is an aryl) with ammonia and hydrogen in the presence of a hydrogenation catalyst while supplying the arylacrolein expressed by general formula (1) to the reaction system.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a compound represented by the general formula (2): R-CH ₂ CH ₂ CH ₂ NH ₂ (2) (wherein R represents an aryl group), which is useful, for example, as a pharmaceutical intermediate. A process for the preparation of the indicated 3-arylpropylamines.

[0002]

2. Description of the Related Art As a method for producing 3-arylpropylamine, for example, the following method for producing 3-phenylpropylamine from cinnamaldehyde as a starting material is known. The oxime produced by reacting cinnamaldehyde with hydroxyamine is catalytically hydrogenated to give 3
-Method for producing phenylpropylamine [Journ
al of American Chemical S
ociety, 54, 306 (1932), Journal
al of American Chemical S
chemistry, 55, 2051 (1933), etc.], and a method of producing 3-phenylpropylamine by reacting phenylhydrazone produced by reacting cinnamaldehyde with phenylhydrazine [Synthetic].
Communication, 7, 71 (197
7)], a method for producing 3-phenylpropylamine by reacting cinnamaldehyde with ammonia and hydrogen [Bull. Soc. Cim. Fr. , 104
5 (1950)].

[0003]

However, the above-mentioned conventional method has the following problems. In this method, hydroxyamine used for producing the oxime is expensive, and the catalytic hydrogenation yield is as low as 42%. Method 3
-Phenylpropylamine can be produced in a high yield (60%), but phenylhydrazine used for producing phenylhydrazone is expensive and separation from aniline as a by-product is complicated. In the other method, the yield of 3-phenylpropylamine is as low as 17%. As described above, any of these methods is industrially unsatisfactory. Therefore, the present invention
It is an object of the present invention to provide a method capable of easily producing 3-phenylpropylamine represented by the general formula (2) with high yield.

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies in order to solve the above problems. As a result, an arylacrolein represented by the general formula (1): R-CH = CH-CHO (1) (wherein R represents an aryl group) (hereinafter simply referred to as arylacrolein) is converted into ammonia and hydrogen was reacted general formula in the presence of a hydrogenation catalyst _{(2): R-CH 2} CH 2 CH 2 NH 2 (2) ( wherein, R is as defined above.) 3-aryl-propylamine represented by (Hereinafter, simply referred to as 3-arylpropylamine) by reacting while supplying arylacrolein into the reaction system,
The present inventors have found that 3-arylpropylamine can be easily produced in high yield, and have completed the present invention.

That is, the present invention provides a method for producing 3-arylpropylamine by reacting arylacrolein, ammonia and hydrogen in the presence of a hydrogenation catalyst, while supplying arylacrolein into a reaction system. And a method for producing a 3-arylpropylamine.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be specifically described below. In the arylacrolein used in the present invention, the aryl group represented by R in the general formula (1) includes a phenyl group and a naphthyl group which may have an alkyl group or an alkyloxy group in the aromatic ring. And a heteroaromatic hydrocarbon group such as a pyridyl group and a quinonyl group which may have a substituent of an alkyl group or an alkyloxy group in the ring. In the above, as the alkyl group having a ring, a methyl group, an ethyl group,
Examples include a propyl group and the like, and examples of the alkyloxy group include a methoxy group and an ethoxy group. Specific examples of arylacrolein include, for example, cinnamaldehyde, methoxycinnamaldehyde, pyridineacrylaldehyde and the like.

The hydrogenation catalyst used in the present invention includes:
Expanded cobalt and expanded nickel, and those obtained by modifying these with various metals, are available as commercial products. Modified metals include iron, chromium, molybdenum, vanadium, tungsten, manganese, lead, copper,
Silver, tin, platinum, palladium and the like are mentioned, and are often used for the modification. The amount of the hydrogenation catalyst to be used is generally 0.01 to 1 part by weight of arylacrolein.
0.3 parts by weight, preferably 0.2 parts by weight.

The amount of ammonia used is usually 1 to 10 mol, preferably 1 to 3 mol, per 1 mol of arylacrolein.

In the present invention, a solvent is usually used. Examples of the solvent include organic solvents such as alcohols such as methanol, ethanol and propanol, aromatic hydrocarbons such as benzene, toluene and xylene, and ethers such as tetrahydrofuran, and one or more of these can be used. Preferred solvents are alcohols. The amount of the solvent to be used is generally 0.1 to 10 parts by weight, preferably 1 to 5 parts by weight, per 1 part by weight of arylacrolein.

In the present invention, it is important to carry out the reaction while supplying aryl acrolein into the reaction system. The supply rate of acrolein into the reaction system can be wide, but is usually 0.5 to 5.0 g / (hr · g-catalyst), preferably 1. 5 to 3.5 g / (hr · g-catalyst). If the feed rate is higher than the above range, the yield will decrease, and if the feed rate is too slow, the productivity will decrease.

[0011] The reaction temperature is usually 70 to 130 ° C, preferably 90 to 100 ° C. The hydrogen pressure is usually 1.
The pressure is 0 to 5.0 Pa, preferably 2.0 to 3.0 Pa.

In order to carry out the present invention, for example, a reaction of a mixture of ammonia, a hydrogenation catalyst and a solvent may be carried out while maintaining the above-mentioned temperature and hydrogen pressure while supplying arylacrolein at the above-mentioned supply rate.

In order to recover 3-arylpropylamine produced by the reaction from the reaction mixture after completion of the reaction, for example, after completion of the reaction, the obtained reaction mixture is filtered to remove the catalyst, and then the filtrate is distilled. Thus, the 3-arylpropylamine can be separated and purified.

[0014]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to the following examples.

Example 1 An autoclave was charged with developing nickel (26.4 g) and methanol (132.2 g), and then ammonia (34 g, 2 mol) was added. After raising the internal temperature of the autoclave to 90 ° C. and introducing hydrogen to a pressure of 3 MPa, cinnamaldehyde (132.
2 g, 1 mol) were fed into the reactor over 2 hours. At this time, the feed rate of cinnamaldehyde was 2.5 g /
(Hr · g-catalyst). After the completion of the supply of cinnamaldehyde, the internal temperature of the autoclave was kept at 80 ° C. and the pressure was kept at 3 MPa for 0.5 hour. Thereafter, the resulting reaction mixture was filtered to remove the catalyst, and then the filtrate was distilled to give 3-107 as a fraction at 107-112 ° C / 2.4 kPa.
93.8 g (0.69 mol, 69% yield) of phenylpropylamine were obtained.

Comparative Example 1 An autoclave was developed. Nickel (26.4 g), methanol (132.2 g), cinnamaldehyde (132.
2 g, 1 mol). Add ammonia to (25.5
g, 1.5 mol), and the pressure was adjusted to 3 MPa with hydrogen. The internal temperature of the autoclave was raised to 90 ° C. and reacted for 2 hours. Then, the obtained reaction mixture was used in Example 1
And then treated with 3-phenylpropylamine.
8 g (0.28 mol, 28% yield) were obtained.

Claims (2)

[Claims] 1. An arylacrolein represented by the general formula (1): R—CH ＝ CH—CHO (1) wherein R represents an aryl group, ammonia and hydrogen in the presence of a hydrogenation catalyst. To produce a 3-arylpropylamine represented by the general formula (2): R—CH ₂ CH ₂ CH ₂ NH ₂ (2) (wherein R is as defined above). Wherein the reaction is carried out while supplying an aryl acrolein represented by the general formula (1). 2. Aryl acrolein is added to the reaction system in an amount of 0.1 to 2%.
2. The method according to claim 1, wherein the catalyst is supplied at 5 to 5.0 g / (hr · g-catalyst).
The described method.