JPH07138209A - Production of halogen-containing aminomethyl compound - Google Patents

Abstract

PURPOSE:To provide a production method for efficiently obtaining a halogen- containing aminomethyl compound by using a halogen-containing nitrile compound as a raw material, suppressing formation of by-products. CONSTITUTION:In production of a halogen-containing aminomethyl compound by reducing a halogen-containing nitrile compound with ammonia in the presence of a heterogeneous system-based catalyst, a production method for obtaining the halogen-containing aminomethyl compound characterized by adding an ammonium salt to the reaction system in the reduction reaction is provided.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing a halogen-containing aminomethyl compound. INDUSTRIAL APPLICABILITY The halogen-containing aminomethyl compound according to the present invention is useful in the fields of medicine, agricultural chemicals, etc., especially as an intermediate for herbicides and insecticides.

[0002]

2. Description of the Related Art Generally, as a method of obtaining an aminomethyl compound from a nitrile compound as a raw material, there is a method of reducing a nitrile group in the nitrile compound to give an aminomethyl group and obtaining a corresponding aminomethyl compound. This reduction reaction is roughly classified into a method using a reducing agent such as a metal hydride and a method using hydrogenation, as shown in the following reaction formula.

[0003]

[Chemical 1]

In the formula, R is alkyl such as methyl or ethyl; substituted or unsubstituted aryl such as phenyl, tolyl or naphthyl; substituted or unsubstituted,
A heterocyclic group such as pyridyl or furyl; or a compound to which these are bonded. Among the above, as a method using a reducing agent, for example, lithium aluminum hydride (LiAlH
₄ ), aluminum hydride (AlH ₃ ), sodium borohydride (NaBH ₄ ) and the like. In addition, as a method by hydrogen addition, for example, Co
There are methods such as hydrogenation using a homogeneous catalyst such as Cl ₂ and Co ₂ (CO) ₈ and hydrogenation using a heterogeneous catalyst such as Raney nickel, Raney cobalt and palladium carbon.

However, in the method using a reducing agent,
There is a problem that the reducing agent is expensive and economically disadvantageous, many of the reducing agents are water-prohibited substances, and the handling operation is complicated. This method is not suitable for use on a general industrial scale. On the other hand, in the method using catalytic hydrogenation, the catalyst is expensive and economically disadvantageous, and it is necessary to invest in high-pressure equipment essential for the catalytic reaction. There was a problem that it was technically difficult to increase the yield.

Among the aminomethyl compounds, the method for producing a halogen-containing aminomethyl compound having a halogen element such as chlorine, bromine or fluorine together with an aminomethyl group in the compound using a halogen-containing nitrile compound as a raw material is as described above. A method using the reducing agent described above, a method using hydrogenation with a catalyst, and the like are known. However,
In the above case, in addition to the above-mentioned problems, there is a problem in that the halogen itself is also reduced to form an aminomethyl compound (hereinafter referred to as a dehalogenated compound) as a by-product, which lowers the yield of the target product.

In particular, when a halogen-containing aromatic nitrile compound is used as a raw material, and when the substitution position of the halogen and the cyano group is the ortho or para coordination, the dehalogenation by-product tends to increase. However, there is no effective means for suppressing the dehalogenation by-product.

[0008]

[Chemical 2]

In the formula, X represents halogen. by the way,
In the step of producing a halogen-containing aminomethyl compound by reducing a halogen-containing nitrile compound, it has been known that by-product of a secondary amine compound can be suppressed by using ammonia as an additive during the reaction. However, the dehalogenation by-product could not be suppressed even by using this method. Although the reduction reaction in the case where the halogen-containing nitrile compound is a chlorocyanopyridine compound by the above method is disclosed in DE3726993 specification, the yield thereof is as extremely low as 58%, which is not practical.

[0010]

In view of the above, in the present invention, when a halogen-containing nitrile compound is used as a raw material to produce a halogen-containing aminomethyl compound, a secondary amine compound is prevented from being produced as a by-product, and a dehalogenation by-product is produced. It is an object of the present invention to provide a method for efficiently obtaining a halogen-containing aminomethyl compound by suppressing the growth of raw materials.

[0011]

The gist of the present invention is to prepare a halogen-containing aminomethyl compound by adding a halogen-containing nitrile compound in the presence of a heterogeneous catalyst with ammonia and an ammonium salt to carry out a hydrogenation reaction. And then
It is in the process of reducing the nitrile group of a halogen-containing nitrile compound. Hereinafter, the present invention will be described in detail.

The halogen-containing nitrile compound used as a raw material in the present invention includes a compound in which an aliphatic hydrocarbon is substituted with a halogen and a nitrile group, a compound in which an aromatic hydrocarbon is substituted with a halogen and a nitrile group, and a heterocycle. Examples include compounds in which the formula compound is substituted with halogen and a nitrile group, compounds in which a part of the compound to which the above-mentioned aliphatic hydrocarbon, aromatic hydrocarbon, heterocyclic compound, etc. are bound is substituted with a halogen and a nitrile group. . Examples of the halogen include chlorine, bromine, fluorine and iodine.

Examples of the halogen-containing nitrile compound include p-chlorobenzonitrile, o-chlorobenzonitrile, m-chlorobenzonitrile and 1-chloro-2-
Cyanonaphthalene, 1-chloro-4-cyanonaphthalene, o-chlorobenzyl cyanide, p-chlorobenzyl cyanide, 3-chlorophthalonitrile, 4-chlorophthalonitrile, 2-chloroisophthalonitrile, 4-chloroisophthalo Nitrile, 5-chloroisophthalonitrile, 2-chloroterephthalonitrile, 2,4-dichlorobenzonitrile, 2,6-dichlorobenzonitrile,
3,5-dichlorobenzonitrile, 2-chloro-3-cyanopyridine, 2-chloro-4-cyanopyridine, 2-
Chloro-5-cyanopyridine, 2,6-dichloro-3-
Cyanopyridine, 2,6-dichloro-4-cyanopyridine, chloroacetonitrile, 3-chloropropionitrile, 2-chloropropionitrile, 2,3-dichloropropionitrile, 1-chloro-1,2-ethanedicyanide, p-bromobenzonitrile, o-bromobenzonitrile, m-bromobenzonitrile, 1-bromo-2-cyanonaphthalene, 1-bromo-4-cyanonaphthalene,
o-bromobenzyl cyanide, p-bromobenzyl cyanide, 3-bromophthalonitrile, 4-bromophthalonitrile, 2-bromoisophthalonitrile, 4-bromoisophthalonitrile, 5-bromoisophthalonitrile, 2
-Bromoterephthalonitrile, 2,4-dibromobenzonitrile, 2,6-dibromobenzonitrile, 3,5-
Dibromobenzonitrile, 2-bromo-3-cyanopyridine, 2-bromo-4-cyanopyridine, 2-bromo-
5-cyanopyridine, 2,6-dibromo-3-cyanopyridine, 2,6-dibromo-4-cyanopyridine, bromoacetonitrile, 3-bromopropionitrile, 2-
Examples include bromopropionitrile, 2,3-dibromopropionitrile, 1-bromo-1,2-ethanedicyanide, and the like.

The ammonium salt used in the present invention is not particularly limited, and examples thereof include ammonium chloride, ammonium bromide, ammonium sulfate and ammonium nitrate. The ammonium salt is preferably a salt of the same halogen and ammonium as the halogen of the halogen-containing nitrile compound used in the present invention. For example, when the halogen in the halogen-containing nitrile compound is chlorine, ammonium chloride is used, and when the halogen is bromine, ammonium bromide is preferably used. The amount of the ammonium salt used is 0.1 to 0.1 with respect to the halogen-containing nitrile compound.
It is 5 times the molar amount. When the amount is less than 0.1 times the molar amount, the yield of the desired product is lowered or the progress of the dehalogenation reaction increases, and when the amount is more than the 5 times molar amount, separation after the reaction,
It is not preferable because purification becomes difficult.

In the present invention, the above ammonium salt is added together with ammonia during the reaction. The addition of the above ammonia to the reaction system may be either gas blowing into the reaction solvent, or any of the water-containing states such as ammonia water, and a saturated ammoniacal organic solvent obtained by a method of saturating the ammonia gas by aeration with an organic solvent. May be used as a reaction solvent.

The heterogeneous catalyst used in the present invention is a catalyst capable of reducing a nitrile group,
It is not particularly limited, and examples thereof include Raney nickel, Raney cobalt, and palladium carbon. Above all,
Raney nickel and Raney cobalt are preferably used because the production of dehalogenated compounds is more effectively suppressed.

The pressure during the reaction of the present invention is not particularly limited,
Usually, the atmospheric pressure to 10 atm (gauge) may be taken into consideration in consideration of legal restrictions and economic effects such as capital investment. Although it changes depending on the reaction temperature, in order to complete the reaction in 1 to 2 hours, it is preferable to carry out at 5 to 9 atm.

The temperature of the above reaction is usually 0 to 80 ° C, preferably 15 to 60 ° C. When the reaction temperature is higher than 80 ° C, a large amount of tar-like substances are produced, and when the reaction temperature is lower than 0 ° C, the reaction rate becomes slow, which is not economical.

The above reaction can be carried out in a solvent. The solvent is not particularly limited as long as it is a solvent that dissolves a substrate, and for example, methanol as an alcohol solvent,
Ethanol, i-propanol, etc .; ether solvents such as diethyl ether, diisopropyl ether, dioxane, THF, etc .; hydrocarbon solvents such as hexane, cyclohexane, octane, toluene, xylene, etc .; ester solvents such as ethyl acetate, propyl acetate, etc. To be These solvents may be used alone or in combination of two or more.

[0020]

As described above, a synergistic effect is observed by adding together an ammonia salt together with ammonia, which was conventionally added at the time of reaction in order to suppress the by-product of the secondary amine compound. Not only the by-product of the above is further suppressed, but also the by-product of the dehalogenation product formed by reducing the active halogen in the molecule can be suppressed at the same time.

[0021]

The present invention will be described in more detail below with reference to examples of the present invention, but the present invention is not limited to these examples. Example 1 10.7 g (0.07) of 2-chloro-5-cyanopyridine
7 mol) and 8.2 g (0.154 mol) of ammonium chloride are dissolved in 100 ml of saturated ammoniacal methanol obtained by allowing ammonia gas to pass through and saturated with methanol. The reaction was performed at 9 kg / cm ² G and room temperature for 1 hour.
After filtering the catalyst, the solvent was distilled off. The concentrate was neutralized with 30% sodium hydroxide and extracted with ethyl acetate. The organic layer was concentrated and then distilled under reduced pressure to obtain 9.7 g of 2-chloro-5-aminomethylpyridine (yield 88.2%). The boiling point of this product at a pressure of 2 mmHg was in the range of 102 to 105 ° C. When this product was analyzed by gas chromatography, secondary amine was found to have an area percentage of 0.
It was found that 3% and 3-aminomethylpyridine, which is a dechloroform, were produced at 2.8%.

Example 2 10.6 g (0.077 mol) of 4-chlorobenzonitrile and 8.2 g (0.154 mol) of ammonium chloride were dissolved in 100 ml of saturated ammoniacal methanol, and 5 g of Raney cobalt was added thereto. Reaction was carried out in an autoclave at a hydrogen pressure of 9 kg / cm ² G and 40 ° C. for 1 hour. After filtering the catalyst, the solvent was distilled off. The concentrate was neutralized with 30% sodium hydroxide and extracted with ethyl acetate. After concentrating the organic layer,
Distilled under reduced pressure to give 4-chlorobenzylamine 10.0 g.
(Yield 91.7%) was obtained. The pressure of this thing is 15mmH
The boiling point at g was in the range of 106-107 ° C.

Example 3 14.0 g (0.077 mol) of 4-bromobenzonitrile
), Ammonium bromide 15.1 g (0.154 mol)
Was dissolved in 100 ml of saturated ammoniacal methanol,
Add 5 g of Nanickel and water in an autoclave.
Element pressure 5kg / cm ²G, reacted at room temperature for 3 hours. Catalyst
After filtration, the solvent was distilled off. Add 30% caustic soda to the concentrate
The mixture was neutralized and extracted with ethyl acetate. After concentrating the organic layer,
Distillation under reduced pressure is carried out, and 11.2 g of 4-bromobenzylamine
(Yield 78.3%) was obtained. The pressure of this thing is 15mmH
The boiling point at g was in the range of 126-127 ° C.

Example 4 6.9 g (0.077 mol) of 3-chloropropionitrile and 8.2 g (0.154 mol) of ammonium chloride were dissolved in 100 ml of saturated ammoniacal methanol, and 5 g of Raney nickel was added thereto. The reaction was carried out in an autoclave at a hydrogen pressure of 9 kg / cm ² G and room temperature for 1 hour. After filtering the catalyst, the solvent was distilled off. The concentrate was neutralized with 30% sodium hydroxide and extracted with ethyl acetate. Hydrogen chloride 3 in the organic layer
g was blown in, filtered and dried to obtain 9.2 g of 3-chloropropylamine hydrochloride (yield 92.0%). The melting point of this product was in the range of 148 to 150 ° C.

Comparative Example 1 The reaction was carried out by the same method and conditions as in Example 1 except that ammonium chloride was not added. As a result, 6.3 g of 2-chloro-5-aminomethylpyridine (yield 57.
3%) was obtained. This product was analyzed by gas chromatography to find that the secondary amine had an area percentage of 15.2.
%, And the dechloroform was produced at 8.5%.

[0026]

INDUSTRIAL APPLICABILITY According to the present invention, in the reduction reaction of a halogen-containing nitrile compound, when an ammonium salt is added in addition to ammonia which has been conventionally used during the reaction, the secondary amine by-product is further reduced. Further, the production of by-products such as dehalogenated compounds, which could not be suppressed when ammonia alone is added, can be suppressed, and the halogen-containing aminomethyl compound can be produced extremely efficiently.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁶ Identification number Internal reference number FI Technical indication C07D 213/61 // C07B 61/00 300 (72) Inventor Mikio Yamamoto Miyanishi, Kami-gun, Kako-gun Miyanishi No. 346 No. 1 Sumitomo Seika Co., Ltd. 1st Laboratory

Claims (7)

[Claims] 1. A halogen-containing nitrile compound, wherein ammonia and an ammonium salt are added in the presence of a heterogeneous catalyst to carry out a hydrogenation reaction to reduce the nitrile group of the halogen-containing nitrile compound. A method for producing an aminomethyl compound. 2. The ammonium salt is ammonium chloride,
The production method according to claim 1, which is ammonium bromide, ammonium sulfate or ammonium nitrate. 3. The method according to claim 1, wherein the ammonium salt is added in an amount of 0.1 to 5 times the molar amount of the halogen-containing nitrile compound. 4. The method according to claim 1, wherein the heterogeneous catalyst is Raney nickel or Raney cobalt. 5. The method according to claim 1, wherein the pressure range of the reduction reaction is 0 to 10 atm (gauge). 6. The production method according to claim 1, wherein the reaction temperature of the reduction reaction is 0 to 80 ° C. 7. The production method according to claim 1, wherein the reaction solvent for the reduction reaction is methanol.