JPH08333308A - Production of n,n'-bis(3-aminopropyl diaminoalkane - Google Patents

Abstract

PURPOSE: To obtain an N,N'-bis(3-aminopropyl)diaminoalkane useful as an intermediate for pharmaceuticals or agrochemicals containing little amount of by- products, easy to be purified in high selectivity and high yield by a catalytic hydrogenation of an N,N'-bis(2-cyanoethyl)diaminoalkane in a mixture of a solvent, ammonia and a catalyst. CONSTITUTION: The compound of the formula; H2 NCH2 CH2 CH2 NH-R-NHCH2 CH2 CH2 NH2 is obtained by adding (B) a compound of the formula; NCCH2 CH2 NH-R-NHCH2 CH2 CN (R is a 2-12C saturated hydrocarbon residue) to (A) a mixture of (A1 ) methyl alcohol, butyl alcohol, (A2 ) ammonia and (A3 ) a hydrogeneration catalyst such as Raney Nickel, platinum-group metal, etc., to effect catalytic hydrogenation using (C) hydrogen.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a process for producing N, N'-bis (3-aminopropyl) -diaminoalkane which is useful as an intermediate for medicines and agricultural chemicals. More specifically, N, N '
-N, N'-bis (3-aminopropyl) -by catalytic hydrogenation of bis (2-cyanoethyl) -diaminoalkane
The present invention relates to a method for producing diaminoalkane.

[0002]

2. Description of the Related Art Conventionally, a method for producing N, N'-bis (3-aminopropyl) -diaminoalkane has been described in, for example, N, N.
As a method for producing ′ -bis (3-aminopropyl) -1,4-diaminobutane, a solvent, N, N′-
Bis (2-cyanoethyl) -1,4-diaminobutane,
A method in which a Raney nickel catalyst and ammonia are charged and a catalytic hydrogenation reaction of N, N′-bis (2-cyanoethyl) -1,4-diaminobutane is carried out at 140 ° C. under heating and stirring while introducing hydrogen [J. Am. Chem. So
c. , 70, 2666 (1948)] are known.

[0003]

However, according to the above-mentioned conventional method, the yield of N, N'-bis (3-aminopropyl) -1,4-diaminobutane, which is the object, is as low as about 51%. It is not a satisfactory method for producing'-bis (3-aminopropyl) -diaminoalkane. The present invention provides a method capable of producing N, N′-bis (3-aminopropyl) -diaminoalkane in high yield by catalytic hydrogenation reaction of N, N′-bis (2-cyanoethyl) -diaminoalkane. The purpose is to

[Means for Solving the Problems]

The present inventors have made extensive studies to solve the problems of the above conventional method. First, when the cause of the low yield of this conventional method was examined, it was found that the cause was that the raw material N, N′-bis (2-cyanoethyl) -diaminoalkane existing in the reaction system was decomposed. It was Therefore, further studies were conducted to suppress this decomposition and produce N, N'-bis (3-aminopropyl) -diaminoalkane in a high yield. As a result, first, the reactor was charged with a solvent, ammonia and a hydrogenation catalyst, and the resulting mixture was charged with N,
If the catalytic hydrogenation reaction is carried out while adding N'-bis (2-cyanoethyl) -diaminoalkane, N, N
It was found that ′ -bis (3-aminopropyl) -diaminoalkane can be produced in high yield, and the present invention has been completed.

That is, the present invention provides a compound of the general formula (1): NCCH ₂ CH ₂ NH-R-NHCH ₂ CH ₂ CN (1) in the presence of a solvent, ammonia and a hydrogenation catalyst. . to an aliphatic hydrocarbon residue having 2 to 12) N represented by, N'- bis (2-cyanoethyl) - general formula contacted hydrogenation diamino alkane with hydrogen (2): H _{2 NCH 2 CH 2 CH 2 NH-} R-NHCH 2 CH 2 CH 2 NH 2 (2) ( wherein, R is as defined above.) is represented by N, N'-bis (3-aminopropyl) - diamino In producing an alkane, a catalytic hydrogenation reaction is carried out while adding N, N'-bis (2-cyanoethyl) -diaminoalkane represented by the general formula (1) to a mixture of a solvent, ammonia and a hydrogenation catalyst. N, N'-bis (3 -Aminopropyl) -diaminoalkane.

In the present invention, N, N 'represented by the general formula (1) is added to a mixture of a solvent, ammonia and a hydrogenation catalyst.
-Bis (2-cyanoethyl) -diaminoalkane [hereinafter referred to as N, N'-bis (2-cyanoethyl) -diaminoalkane (1). ], It is important to carry out the catalytic hydrogenation reaction. When the reaction is carried out in this way, N, N'-bis (2-cyanoethyl) -diaminoalkane (1) is immediately hydrogenated when introduced into the reaction system and does not accumulate in the reaction system. Therefore, side reactions such as decomposition of N, N'-bis (2-cyanoethyl) -diaminoalkane (1) are suppressed, and N, N 'represented by the general formula (2) can be obtained in high yield and high selectivity. -Bis (3-aminopropyl) -diaminoalkane [hereinafter, N, N'-bis (3-
Aminopropyl) -diaminoalkane (2). ]
Can be manufactured.

In the N, N'-bis (2-cyanoethyl) -diaminoalkane (1) used in the present invention, R in the formula is an aliphatic hydrocarbon residue having 2 to 12 carbon atoms and an ethylene group. , Polymethylene groups such as trimethylene group, tetramethylene group, pentamethylene group, hexamethylene group, heptamethylene group, octamethylene group, nonamethylene group, decamethylene group, dodecamethylene group, and propylene group, 2-methylpropylene group, 1, A branched aliphatic hydrocarbon residue such as a 3-pentylene group or a 2-methyl-1,5-pentylene group is included. N, N'-bis (2
-Cyanoethyl) -diaminoalkane (1) is described in, for example, J. Am. Chem. Soc. , 70, 2666
It can be easily obtained from a diaminoalkane and acrylonitrile as described in (1948).

Specific examples of N, N'-bis (2-cyanoethyl) -diaminoalkane (1) include N, N'-bis (2-cyanoethyl) -1,2-diaminoethane,
N, N'-bis (2-cyanoethyl) -1,2-diaminopropane, N, N'-bis (2-cyanoethyl)-
1,3-diaminopropane, N, N'-bis (2-cyanoethyl) -1,2-diamino-2-methylpropane,
N, N'-bis (2-cyanoethyl) -1,4-diaminobutane, N, N'-bis (2-cyanoethyl) -1,
3-diaminopentane, N, N'-bis (2-cyanoethyl) -1,5-diaminopentane, N, N'-bis (2-cyanoethyl) -1,5-diamino-2-methylpentane, N, N ′ -Bis (2-cyanoethyl) -1,
6-diaminohexane, N, N'-bis (2-cyanoethyl) -1,7-diaminoheptane, N, N'-bis (2-cyanoethyl) -1,8-diaminooctane,
N, N'-bis (2-cyanoethyl) -1,9-diaminononane, N, N'-bis (2-cyanoethyl) -1,
Examples thereof include 10-diaminodecane, N, N'-bis (2-cyanoethyl) -1,12-diaminododecane.

Examples of the hydrogenation catalyst used in the catalytic hydrogenation reaction of the present invention include Raney catalysts such as Raney nickel and Raney cobalt, and platinum group catalysts such as palladium, rhodium, ruthenium and iridium. As the platinum group catalyst, used is an active carbon, alumina, silica, diatomaceous earth, pumice, zeolite, molecular sieve or other carrier which is inert to the catalytic hydrogenation reaction and on which 0.1 to 10% by weight of the platinum group metal is supported. You can also do it.

When the Raney catalyst is used, the amount of hydrogenation catalyst used is N, N'-bis (2-cyanoethyl) as a raw material.
1 to 1 part by weight of diaminoalkane (1) is usually 1 to
It is 50% by weight, preferably 10 to 30% by weight. When a platinum group catalyst is used as the hydrogenation catalyst, for example, when a catalyst in which 5% by weight of palladium is supported on activated carbon is used, the amount used is N, N'-bis (2-cyanoethyl) -diaminoalkane ( 1) It is usually 0.1 to 20% by weight, preferably 0.5 to 10% by weight, based on 1 part by weight. When using other platinum group catalyst, the amount containing the same amount of platinum group metal as when using the above palladium catalyst may be used.

When the amount of the hydrogenation catalyst used is less than the above range, the reaction rate of the catalytic hydrogenation reaction decreases, so that N, N'-bis (2-cyanoethyl) -diaminoalkane (1) is added to the reaction system. Is easy to accumulate. As a result, N, N
A side reaction such as decomposition of the ′ -bis (2-cyanoethyl) -diaminoalkane (1) occurs, and the yield and selectivity of the target N, N′-bis (3-aminopropyl) -diaminoalkane (2). Will be reduced. Therefore,
In order to prevent N, N'-bis (2-cyanoethyl) -diaminoalkane (1) from accumulating in the reaction system, the compound must be slowly and gradually supplied into the reaction system by catalytic hydrogenation. The reaction takes a long time. When the amount of the hydrogenation catalyst used is larger than the above range, there is no particular problem, but it is preferable to carry out the hydrogenation catalyst within the above range from an economical viewpoint.

The solvent used in the present invention is inert to the catalytic hydrogenation reaction and contains N, N'-bis (2-cyanoethyl) -diaminoalkane (1) and N, N'-.
Bis (3-aminopropyl) -diaminoalkane (2)
Any substance that dissolves The solvent is also used for the purpose of dispersing the hydrogenation catalyst in the reaction system during the catalytic hydrogenation reaction to promote the catalytic hydrogenation reaction. As such a solvent, alcohols such as methyl alcohol, ethyl alcohol, isopropyl alcohol and butyl alcohol can be preferably used, but the solvent is not limited thereto. The amount of the solvent used depends on the kind of the solvent and N, N′-bis (2-cyanoethyl) -diaminoalkane (1) and N, N′-bis (3-aminopropyl) -diaminoalkane (2). It cannot be uniquely determined by the solubility, and it may be used in an amount that meets the above purpose and in consideration of container efficiency.

In the present invention, ammonia coexists in the reaction system. The amount of ammonia used is 5 to 40% by weight, preferably 15 to 35% by weight, based on 1 part by weight of N, N'-bis (2-cyanoethyl) -diaminoalkane (1). When the amount of ammonia used is less than the above range, side reactions such as decomposition of N, N'-bis (2-cyanoethyl) -diaminoalkane (1) are likely to occur. On the other hand, when the amount of ammonia used is more than the above range, the hydrogen concentration in the reaction system decreases and the catalytic hydrogenation reaction is less likely to occur, and N, N'-bis (2-cyanoethyl)- This leads to the accumulation of diaminoalkane (1).

The reaction temperature of the catalytic hydrogenation reaction can be widely selected, but is usually 50 to 200 ° C., preferably 7
It is 0 to 130 ° C. If the reaction temperature is lower than the above range, the reaction rate decreases, and N, N'-bis (2-cyanoethyl) -diaminoalkane (1) is likely to accumulate in the reaction system, which is not preferable. If the reaction temperature is higher than the above range, side reactions such as decomposition tend to occur easily.

The reaction pressure of the catalytic hydrogenation reaction is usually 3
It is 0 atm (3.03 × 10 ³ kPa) or more. When the reaction pressure is lower than 30 atm, the reaction rate decreases. The reaction rate increases with an increase in the reaction pressure, which has a favorable effect on the reaction for producing the desired product, but from the viewpoint of economy and workability, the contact hydrogen is preferably 100 atm (1.01 × 10 ⁴ kPa) or less. It is better to carry out a chemical reaction.

The rate of addition of N, N'-bis (2-cyanoethyl) -diaminoalkane (1) to the reaction system in the present invention varies depending on the kind and amount of the compound used, reaction temperature, reaction pressure and the like. Although it cannot be uniquely defined, it was determined according to the reaction rate of the catalytic hydrogenation reaction of the present invention so that N, N'-bis (2-cyanoethyl) -diaminoalkane (1) would not accumulate in the reaction system. Any speed will do.

A preferred example of the method for carrying out the present invention is shown below. First, a pressure reactor is charged with a solvent, a hydrogenation catalyst and ammonia, and the mixture obtained is stirred and the temperature is raised to the above reaction temperature, and hydrogen is introduced into the reactor through the introduction pipe until the reaction pressure is reached. Then, the temperature of the mixture which was heated was maintained under stirring and the N, N
The catalytic hydrogenation reaction is carried out while adding'-bis (2-cyanoethyl) -diaminoalkane (1). N, N '
-Bis (2-cyanoethyl) -diaminoalkane (1)
Since the catalytic hydrogenation reaction proceeds simultaneously with the addition of N,
The catalytic hydrogenation reaction is performed while the reaction pressure is kept constant while successively introducing hydrogen in parallel with the addition of ′ -bis (2-cyanoethyl) -diaminoalkane (1). At the same time as the addition of N, N'-bis (2-cyanoethyl) -diaminoalkane (1) was completed, the catalytic hydrogenation reaction was completed, and N, N'-bis (3-aminopropyl) -diaminoalkane (2) was high. It is produced in high yield with high yield.

In the N, N'-bis (3-aminopropyl) -diaminoalkane (2) obtained by the method of the present invention, R in the formula is N, N'-bis (2-cyanoethyl) -diaminoalkane. The same as in (1). Specific examples of N, N′-bis (3-aminopropyl) -diaminoalkane (2) include N, N′-bis (3
-Aminopropyl) -1,2-diaminoethane, N, N
′ -Bis (3-aminopropyl) -1,2-diaminopropane, N, N′-bis (3-aminopropyl) -1,
3-diaminopropane, N, N'-bis (3-aminopropyl) -1,2-diamino-2-methylpropane,
N, N'-bis (3-aminopropyl) -1,4-diaminobutane, N, N'-bis (3-aminopropyl)-
1,3-diaminopentane, N, N'-bis (3-aminopropyl) -1,5-diaminopentane, N, N'-
Bis (3-aminopropyl) -1,5-diamino-2-
Methyl pentane, N, N'-bis (3-aminopropyl) -1,6-diaminohexane, N, N'-bis (3
-Aminopropyl) -1,7-diaminoheptane, N,
N'-bis (3-aminopropyl) -1,8-diaminooctane, N, N'-bis (3-aminopropyl)-
1,9-diaminononane, N, N'-bis (3-aminopropyl) -1,10-diaminodecane, N, N'-bis (3-aminopropyl) -1,12-diaminododecane and the like can be mentioned. it can.

Isolation and purification of N, N'-bis (3-aminopropyl) -diaminoalkane (2) from the reaction solution is carried out by
For example, after the completion of the catalytic hydrogenation reaction, the reaction solution may be cooled to room temperature, hydrogen and ammonia may be removed, the reaction solution may be filtered to remove the catalyst, and then the obtained filtrate may be distilled. The N, N'-bis (3-aminopropyl) -diaminoalkane (2) thus obtained has a high purity because the content of by-products in the reaction solution after the reaction is extremely small.

[0020]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. In the following examples, the yield is mol% of N, N'-bis (3-aminopropyl) -diaminoalkane (2) with respect to N, N'-bis (2-cyanoethyl) -diaminoalkane (1). .

Example 1 A stainless steel autoclave with an internal volume of 1000 ml equipped with a magnetic stirrer was charged with 200 g of methanol and 60 g of ammonia.
g and Raney cobalt catalyst 65 g were charged, hydrogen was introduced with heating and stirring at 80 ° C., 50 atmospheric pressure (5.06 × 1).
0 ⁴ kPa). Then, in an autoclave at the same temperature, 80% by weight of N, N'-bis (2-cyanoethyl)-
Methanol solution containing 1,4-diaminobutane 40
The catalytic hydrogenation reaction was carried out while 0 g of the mixture was being pressed in for 2 hours.
The catalytic hydrogenation reaction proceeds at the same time when the injection of N, N′-bis (2-cyanoethyl) -1,4-diaminobutane is started,
Since hydrogen was consumed, the catalytic hydrogenation reaction was carried out while successively introducing hydrogen and maintaining the above pressure. Simultaneously with the completion of the injection of N, N'-bis (2-cyanoethyl) -1,4-diaminobutane, hydrogen absorption stopped and the catalytic hydrogenation reaction was completed. After completion of the reaction, the reaction solution was cooled to room temperature, the internal pressure of the reactor was returned to atmospheric pressure, then the reaction solution was filtered to separate the catalyst, and the obtained filtrate was distilled to obtain 98% pure N 2. , N'-bis (2-aminopropyl) -1,4-diaminobutane (292 g, yield 86%) was obtained.

Example 2 80% by weight of N, N'-bis (2-cyanoethyl)-
Except that a methanol solution containing 1,4-diaminobutane was replaced with 400 g of a methanol solution containing 80% by weight of N, N′-bis (2-cyanoethyl) -1,3-diaminopropane, instead of the methanol solution containing 1,4-diaminobutane. Catalytic hydrogenation reaction and post-treatment were carried out in the same manner as in Example 1 to obtain 96% pure N, N.
293 g of ′ -bis (3-aminopropyl) -1,3-diaminopropane was obtained (yield 84%).

Comparative Example 1 In a stainless steel magnetic stirring type autoclave having an internal volume of 1000 ml, 200 g of methanol, 60 g of ammonia, 65 g of Raney cobalt catalyst and 80% by weight of N, N'-bis (2-cyanoethyl) -1,4-diamino. 400 g of a methanol solution containing butane was charged and heated under stirring.
While introducing hydrogen, the internal pressure is 50 atm (5.06 × 10k
Pa) and the catalytic hydrogenation reaction was carried out at 80 ° C. The absorption of hydrogen did not occur within 3 hours after the introduction of hydrogen, and the reaction was completed. After completion of the reaction, the same treatment as in Example 1 was carried out to obtain 253 g of N, N′-bis (2-aminopropyl) -1,4-diaminobutane having a purity of 83% (yield 63%).
I got

[0024]

According to the present invention, N, N'-bis (2-
Since side reactions such as decomposition of cyanoethyl) -diaminoalkane (1) can be suppressed, N, N'-bis (2
-Aminopropyl) -diaminoalkane (2) can be produced in high yield. Moreover, high-purity N, N'-bis (2-aminopropyl) -diaminoalkane (2) can be easily obtained from the reaction solution after the reaction.

Claims (1)

[Claims] 1. A compound represented by the general formula (1): NCCH ₂ CH ₂ NH—R—NHCH ₂ CH ₂ CN (1) in the presence of a solvent, ammonia and a hydrogenation catalyst (wherein R represents a carbon number of 2 to 2). 12 represents an aliphatic hydrocarbon residue, and N, N′-bis (2-cyanoethyl) -diaminoalkane represented by the formula (2) is subjected to catalytic hydrogenation reaction with hydrogen to give a compound represented by the general formula (2): H ₂ NCH ₂ CH _{2 CH 2 NH-R-NHCH} 2 CH 2 CH 2 NH (2) ( wherein, R is as defined above.) N represented by, N'- bis (3-aminopropyl) - producing diaminoalkane In the above, the catalytic hydrogenation reaction is carried out while adding N, N′-bis (2-cyanoethyl) -diaminoalkane represented by the general formula (1) to a mixture of a solvent, ammonia and a hydrogenation catalyst. N, N'-bis (3-aminopropyl) Preparation of di-amino alkanes.