JPH09255655A - Production of aminomethylpyridines containing halogen atom at alpha position - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for producing an aminomethylpyridine containing a halogen atom at the α-position under industrially advantageous conditions of normal pressure or pressure around the normal pressure in high yield and high selectivity. SOLUTION: A cyanopyridine containing a halogen atom at the α-position is catalytially reduced in the presence of ammonia by using a Raney-nickel catalyst to produce an aminomethylpyridine containing the halogen atom at the α-position. A sulfur compound in an amount of 100ppm to 10,000ppm calculated as sulfur atom based on the compound containing the halogen atom is added to the reaction system of the catalytic reduction.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing aminomethylpyridines having a halogen atom at the α-position. The aminomethylpyridines having a halogen atom at the α-position produced by the present invention are useful compounds as intermediates for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art Conventionally, as a method for producing aminomethylpyridines having a halogen atom at the α-position, 2-chloro-
A method of reacting 5-cyanopyridine with hydrogen in the presence of Raney nickel and ammonia to give 2-chloro-5-aminomethylpyridine (German Published Patent No. 372699).
No. 3) is known.

However, the German Published Patent No. 372
In the method described in No. 6993, the yield of 2-chloro-5-aminomethylpyridine is about 50%, and demethylated aminomethylpyridine, which is a by-product, or another molecule of chloromethylpyridine is contained in the amino group. A large amount of bound secondary amine compounds (dimers) are produced, which is difficult to use as an industrial production method.

[0004]

DISCLOSURE OF THE INVENTION The present invention provides a secondary amine compound (dimer) for producing aminomethylpyridines having a halogen atom at the α-position from cyanopyridines having a halogen atom at the α-position as a raw material. It is an object of the present invention to provide a method for efficiently producing aminomethylpyridines having a halogen atom at the α-position, while suppressing the by-production of 1) and suppressing the by-production of a dehalogenated compound.

[0005]

The present invention is directed to aminomethylpyridines having a halogen atom at the α-position by catalytically reducing cyanopyridines having a halogen atom at the α-position in the presence of ammonia using a Raney nickel catalyst. In the reaction system of the catalytic reduction, a sulfur compound is added to the cyanopyridines in an amount of 100 ppm in terms of sulfur atom.
The present invention relates to a method for producing aminomethylpyridines, which is characterized by adding 1 to 10,000 ppm.

That is, according to the present invention, the dehalogenation reaction at the α-position is effectively suppressed, and the desired aminomethylpyridines having a halogen atom at the α-position can be obtained with high selectivity and high yield. Is. According to the conventional wisdom, various sulfur compounds are known as catalyst poisons for Raney nickel catalysts, but the present invention surprisingly uses a specific amount of such a sulfur compound, and surprisingly, in particular, dehalogenation at the α-position of a side reaction. It was discovered that the chemical reaction is effectively suppressed.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Preferred specific embodiments of the present invention will be described below. In the present invention, the aminomethylpyridines having a halogen atom at the α-position are in a solvent containing cyanopyridines having a halogen atom at the α-position,
Usually 0.05 to 1 relative to 1 part by weight of the cyanopyridine
Usually 20 to 15 in the presence of parts by weight of Raney nickel catalyst.
Hydrogen is added in a temperature range of 0 ° C., preferably in a temperature range of 10 to 60 ° C. in order to enhance suppression of dehalogenation and dimerization, and a hydrogen pressure is usually 1 to 100 atm, preferably 1 to 10 atm. After the completion of the reaction, the Raney nickel catalyst is filtered off, the solvent is distilled off, and the residue is obtained by separation by distillation. At this time, it is common to continuously supply the amount of hydrogen consumed by the reaction and maintain the hydrogen pressure, but the amount required to complete the reaction is charged in advance to consume a stoichiometric amount of hydrogen. The reaction may be terminated when the reaction is completed.

The amount of ammonia used is 10 to 200% by weight based on the cyanopyridines having a halogen atom at the α-position.
However, from the viewpoint of reaction rate and control of side reactions,
A range of 20 to 100% by weight is preferable. The Raney nickel catalyst used in the present invention has a sedimentation rate of 1.0 cm / sec or less, preferably 0.8 cm / sec, as described in detail in the inventors' prior application (Japanese Patent Application No. 6-187423). Seconds or less, more preferably 0.6 cm / second or less, and hydrogenated phenol activity of 1000 H ₂ ml / gNi / hour or less,
It is preferably 600 H ₂ ml / g Ni / hour or less, and A
Those having an I content of 3 to 8% by weight with respect to the Ni content of the Raney nickel catalyst are preferably used.

An example of the production of such a preferable Raney nickel catalyst is, for example, 40 μm in its particle size distribution.
The following ratio is adjusted to 90% or more, and 20 μm or less is adjusted to 50% or more, Raney nickel alloy, more preferably 4
95% or more for a proportion of 0 μm or less and 7 for a proportion of 20 μm or less
The Raney nickel alloy adjusted to 0% or more is reacted with a sodium hydroxide aqueous solution at a temperature range of −20 ° C. to 200 ° C. for 30 minutes to 15 hours to appropriately elute aluminum, and then appropriately washed. .

The sulfur compound used in the present invention is not particularly limited, and for example, hydrogen sulfide and other inorganic sulfur compounds such as sodium sulfate, sodium hydrogen sulfate,
Examples thereof include sulfates such as barium sulfate, magnesium sulfate, copper sulfate, iron sulfate, calcium sulfate, potassium sulfate and ammonium sulfate, and sulfites such as ammonium sulfite, calcium sulfite, sodium sulfite and barium sulfite. Further, dimethyl sulfide as an organic sulfur compound,
Examples thereof include thiazole, thioacetamide, thiobenzoic acid, thioglycolic acid, thiocresol, thioacetic acid, thiourea, thiophenol and thiophene.

The amount of the above sulfur compound used is 100 to 10,000 ppm, preferably 10 based on the sulfur atom in terms of the cyanopyridines having a halogen atom at the α-position as a substrate.
It is in the range of 0 to 2000 ppm, and it also acts as a catalyst poison depending on the reduction reaction conditions to be applied, so it is selected in the range of an amount that does not significantly impair the reaction rate. The solvent used in the present invention is not particularly limited as long as it is an inert solvent for the reduction reaction, but lower alcohol solvents such as methanol, ethanol and butanol, hydrocarbon solvents such as benzene, toluene and cyclohexane, tetrahydrofuran, Examples thereof include cyclic ether solvents such as dioxane, and alcohol solvents are particularly preferable from the viewpoint of the yield of desired aminomethylpyridines. The amount of the solvent used is 1 to 25 times (weight), preferably 10 to 15 times (weight) the amount of the cyanopyridine having a halogen at the α-position.

The cyanopyridines having a halogen atom at the α-position used as a raw material in the present invention are represented by the following general formula (1)

[0013]

Embedded image

(In the above formula, R₁~ R_FourAt least one of
Represents a cyano group, R other than the cyano group ₁~ R_FourAre each
Independently hydrogen atom, phenoxy group, C₁~ C₈The alkyl of
Group, C ₁~ C₈An alkoxy group, an aryl group, or an ant
Group, X represents a halogen atom. )so
expressed. In the above formula, the halogen atom is fluorine.
Atom, chlorine atom, bromine atom, iodine atom and the like.
You. C₁~ C₈The alkyl groups of are methyl and ethyl
Group, propyl group, isopropyl group, butyl group, isobutyl
Group, sec-butyl group, tert-butyl group, pentyl
Group, neopentyl group, tert-pentyl group, hexyl
Group, heptyl group, octyl group, etc.
Examples include a kill group. C₁~ C₈As an alkoxy group
Is a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group.
Poxy, butoxy, isobutoxy, sec-butoxy
Group, tert-butoxy group, pentyloxy group, neope
Butyloxy group, tert-pentyloxy group, hexyl
Ruoxy group, heptyloxy group, octyloxy group, etc.
A straight chain or branched alkoxy group may be mentioned. Aryl
Examples of the group include a phenyl group, a tolyl group and a naphthyl group.
Can be The aryloxy group is a phenoxy group or a trioxy group.
Examples thereof include a ruoxy group and a naphthyloxy group.

Specific cyanopyridines include 2-
Fluoro-3-cyanopyridine, 2-bromo-4-cyanopyridine, 2-iodo-6-cyanopyridine, 2-chloro-5-cyanopyridine, 2-chloro-4-methyl-
5-cyanopyridine, 2-chloro-6-ethoxy-5-
Examples include cyanopyridine and 2-chloro-3,5-dicyanopyridine.

The origin of these cyanopyridines is not particularly limited, but for example, 2-chloro-5-cyanopyridine is a method of chlorinating cyanopyridine (JP-A-64-4).
2467, U.S. Pat. No. 3,591,597, etc.).

[0017]

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 the following examples unless it exceeds the gist. Example 1 2-chloro-5-cyanopyridine 100 g, ethanol 950 g, Raney nickel (wet product) 25 g, 28%
180 g of ammonia water and 0.6 g of sodium sulfate were charged, and the reaction was carried out for 10 hours with vigorous stirring at 20 ° C. while maintaining hydrogen at 1 atm. After completion of the reaction, the catalyst was separated from the reaction solution by filtration and distilled to obtain 2-chloro-5-aminomethylpyridine with a yield of 87%. The dechlorinated product (3-aminomethylpyridine) by-produced at this time was 4% (yield conversion).

The Raney nickel catalyst used in this example has the following properties. Sedimentation rate: 0.55 cm / sec Hydrogenated phenol activity: 490 (H ₂ ml / g Ni /
Time) Al content (Al / Ni): 5.2% BET-total surface area: 80 m2 / gNi Comparative Example A test was conducted in the same manner as in Example 1 without using sodium sulfate. The yield of the obtained 2-chloro-5-aminomethylpyridine was 80%, and the dechlorinated product (3-
Aminomethylpyridine) was 10% (yield conversion).

[0019]

INDUSTRIAL APPLICABILITY According to the present invention, a cyanopyridine having a halogen atom at the α-position is catalytically reduced using a Raney nickel catalyst in the presence of ammonia and a specific amount of a sulfur compound, so that the halogen atom at the α-position is converted. The aminomethylpyridines possessed can be produced in high yield and with high selectivity. In particular, the method of the present invention is an industrially advantageous method because the reaction proceeds sufficiently at or near atmospheric pressure, and the yield of the target product and the selectivity are high.

Claims (3)

[Claims] 1. A method for producing aminomethylpyridines having a halogen atom at the α-position by catalytically reducing a cyanopyridine having a halogen atom at the α-position in the presence of ammonia using a Raney nickel catalyst. A sulfur compound is used in the reduction reaction system, and 100 ppm to 10,000 in terms of sulfur atom in terms of a compound having a halogen atom at the α-position.
A method for producing aminomethylpyridines, which comprises adding ppm. 2. The method according to claim 1, wherein the sulfur compound is an inorganic sulfur compound. 3. The method according to claim 1, wherein the cyanopyridine having a halogen atom at the α-position is 2-chloro-5-cyanopyridine.