JPS62158244A - Production of secondary amine - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as a raw material for perfumery and intermediate for pharmaceuticals, etc., in improved yield without producing by-product, facilitating the separation of the produced compound, by using a water-insoluble organic solvent in the reaction of a benzyl halide derivative with an aqueous solution of a primary amine. CONSTITUTION:The objective compound of formula III is produced by reacting a benzyl halide derivative of formula I (R is alkyl, alkoxy, alkoxyalkyl or halogen; n is 0-3; X is halogen) with an aqueous solution of a primary amine of formula II (Y is alkyl) in a water-insoluble organic solvent at 0-50 deg.C, preferably 10-30 deg.C. The molar ratio of the compound of formula II to the compound of formula I is preferably 2-20, especially 3-15. The water-insoluble organic solvent is an aromatic hydrocarbon, an aliphatic hydrocarbon or an ether and its amount is 1-10pts.wt., preferably 2-5pts.wt. per 1pt. of the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for synthesizing secondary benzylalkylamines, which are important substances as raw materials for fragrances or as intermediates for pharmaceuticals and aS. [Technology] The following methods have been proposed as methods for producing secondary benzylalkylamines.

1) Method for producing methylbenzylamine by reaction of benzyl chloride with an alcoholic solution of methylamine (Archive der P.
harmazie + Vol. 247, p. 564).

2) A method of reacting a primary amine with a halogenated benzyl compound in which the benzene nucleus is substituted with a hydroxyl group or an amino group (
JP-A-50-12030, JP-A-55-3537
Publication No. 4).

6) A method in which a -class amine and an alcohol are subjected to a gas phase reaction in the presence of a catalyst (JP-A-52-4605'r).

4) A method in which a carbonyl compound is reacted with a primary amine and then subjected to reduction treatment (% JP-A-53-59608, JP-A-54-138528).

[Problem that the invention seeks to solve]

Among the conventional techniques, 1) to 3) have low selectivity to secondary amines, and a large amount of tertiary amines are produced as by-products. In addition, 3) requires a high temperature of 200°C or more because it is a gas phase reaction.
) The conditions for hydrogen reduction are also severe, requiring high temperatures of 200°C and high pressures. In addition, in both methods, the reaction is carried out in a homogeneous solvent system, which means that the recovery rate of the unreacted portion of the excess amine is low, and the burden of recovering the solvent and separating the product is large. It has its drawbacks.

[Means for solving problems]

formula! When reacting the halogenated benzyl derivative represented by 2 with an aqueous solution of the primary amine represented by ② and back-passing the secondary benzyl alkyl amine represented by ③, a water-insoluble organic solvent is added. A method for producing a secondary benzylalkylamine.

n (R is an alkyl group, an alkoxy group, an alkoxyalkyl group, or a)f group, n is 0 to 3, x is halobin) YNH2...(It) (Y is an alkyl group) 1 ``Lll The primary amine shown by formula (11) is in a gas state at room temperature and is highly volatile, and industrially it is preferably taken as an aqueous solution at 54K.As a primary amine, especially There is no limit, but the number of carbon atoms is 1 to 3 (1,) (ff)
(III) GV) A primary amine having a linear or branched alkyl group represented by the reaction formula-A. Specifically, methylamine, ethylamine,
n-propylamine and 1-noropylamine.

In this reaction, as shown in reaction formula (A), a tertiary amine (IT) is roughly halogenated benzyl derivative (1
), tertiary amine (IV) is produced as a by-product. A major issue is whether the raw material, the lodenide, reacts with the -class amine (It) or the secondary amine (III). The inventors of the present invention have conducted extensive studies in order to solve this problem.

Halogenated benzyl derivative (1) and -class amine (It
) with an aqueous solution is a two-layer reaction in which the di-halogenated benzyl derivative (1) and the secondary amine (III) and tertiary amine (IV) form an organic layer. There are almost no - Since the amine (1) to be treated exists in the aqueous layer, the raw material a) f fluoride (1) is in a situation where it is extremely likely to react with the secondary amine.

Therefore, the present inventors investigated the addition of various organic solvents in order to suppress the reaction between the halogenated benzyl derivative and the secondary amine in the organic layer, and as a result, they discovered that water-insoluble organic solvents have a remarkable effect. This led to the present invention.

The herocarbonated benzyl derivative (1) used in the present invention has +011 element, bromine, and iodine as CXC, but it is economically advantageous to use it. As the substituent for the benzyl group, there is no particular problem as long as it is the above-mentioned substituent that is inert to primary amines.Specifically, o, m or pOa benzyl, 0
1m or p-bromobenzyl, 0-m- or p-alkylbenzyl, ar- is 2 or 3 substituent of each substituent.

The -class amine (II) is a primary amine having a linear or branched alkyl group having 1 to 3 carbon atoms.Specifically, methylamine, ethylamine, n-noropylamine, i-propylamine It is. The amount used is preferably 2 to 20 times, particularly 3 to 15 times, the molar ratio of the benzyl heronide (I). If it is too small, a large amount of tertiary amine will be produced as a by-product, and if it is too large, it will be economically disadvantageous.

The reaction temperature is preferably 0 to 50°C, particularly 10 to 30°C.
A big fish. If the temperature is too low, the reaction will take a long time, and if the temperature is too high, the rigidity of the tertiary amine will increase.

Solvents that suppress the reaction in the organic layer, which is a feature of the present invention, include aromatic hydrocarbons, aliphatic hydrocarbons, and ethers, and are not particularly limited, but specific examples include benzene, toluene, xylene, ~C3(7) Aliphatic hydrocarbons, diethyl ether, propylene ether, and butyl ether are used. HaC! 1 to 1 as a denated benzyl derivative
0 parts by weight, preferably 2 to 5 parts by weight. If it is too small, it will be ineffective, and if it is too large, it will be economically disadvantageous.

As the reaction method, both batch reaction and continuous reaction methods are possible. In the patch reaction, a water-insoluble organic solvent and an aqueous solution of primary amine (It) are mixed, and the halodanated benzyl fermentation conductor (1) is added all at once, preferably in portions. After the reaction, the product can be easily obtained by separating the organic layer, washing it with water, removing the solvent, and distilling it.

The aqueous layer after the reaction did not contain any secondary amines, and could be reused as is without special recovery or re-addition of the -class amines. According to the present invention, products can be easily separated and -class amines can be used effectively, compared to homogeneous reactions seen in the prior art.

〔Example〕

Example row 1 40% methylamine aqueous solution 77.0. Li' (1 mol) Toluene 75.99 was stirred at 20'C, and 25.3 g (0.2 mol) of benzyl chloride was added in portions over 4 hours.
Stirring was continued for an hour. Analysis of the organic layer by gas chromatography showed that the conversion rate of benzyl chloride was 99%, and benzylmethylamine and dibenzylmethylamine were produced in yields of 64% and 34%, respectively.

Comparative Example 1 The reaction was carried out in the same manner as in Example 1 except that toluene was not used. When the organic layer was extracted with toluene and analyzed, the conversion rate of benzyl chloride was 99%, and the yields of benzylmethylamine and dibenzylmethylamine were 33% and 65%, respectively.

Comparative Example 2 The reaction was carried out in the same manner as in Example 1 except that toluene was not used and the temperature was t-58°C. After extracting the organic layer with toluene, analysis revealed that conversion 4 of benzyl chloride was 45, yielding benzylmethylamine and dibenzylmethylamine.

The rates were 35% and 19%, respectively.

Examples 2 to 11 The results of reactions carried out using various primary amines, benzyl-type hadenides, and organic solvents in the same manner as in the examples are shown in the table.

〔Effect of the invention〕

According to the method of the present invention, secondary amines can be produced with a small amount of by-product tertiary amines, industrially advantageously, and with high selectivity.

Claims (1)

[Claims] When reacting a halogenated benzyl derivative represented by Formula I with an aqueous solution of a primary amine represented by Formula II to produce a secondary benzylalkylamine represented by Formula III, a water-insoluble organic solvent is not used. A method for producing a secondary benzylalkylamine, the method comprising: adding a secondary benzylalkylamine. ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) (R is an alkyl group, an alkoxy group, an alkoxyalkyl group, or a halogen group, n is 0 to 3, and X is a halogen) YNH_2...( II) (Y is an alkyl group) ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(III)