JPH0853417A - Production of aminomethylpyridines having halogen atom at alpha-position - Google Patents

Abstract

PURPOSE:To obtain aminopyridines having a halogen atom at alpha-position in high yield by subjecting cyanopyridines having a halogen atom at alpha-position to catalytic reduction in the presence of a Raney nickel catalyst having a specific property. CONSTITUTION:Cyanopyridines having a halogen atom at alpha position are subjected to catalytic reduction in the presence of a Raney nickel catalyst to provide the objective aminopyridines having halogen atom at alpha-position. In this process, a Raney nickel having <=1.0cm/sec sedimentation rate and <=1000 H2ml/gNi/hr hydrogenated phenol activity is used as the catalyst. A Raney nickel having <=600H2ml/gNi/hr hydrogenated phenol activity and <=0.8cm/sec, especially <=0.6cm/sec sedimentation rate is especially preferable as the catalyst. Al content in the Raney nickel catalyst is preferably 3-8wt.% based on Ni content. 2-Chloro-5-cyanopyridine is preferably used as cyanopyridines having halogen atom at alpha-position.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a process for producing aminomethylpyrimidines having a halogen atom at the α-position, which are useful as intermediates for pharmaceuticals 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 for producing 2-chloro-5-aminomethylpyridine by reacting 5-cyanopyridine with hydrogen in the presence of Raney nickel and ammonia (German Published Patent No. 372).
6993) is known.

[0003]

However, in the above-mentioned production method, the yield of 2-chloro-5-aminomethylpyridine is about 50%, which is not satisfactory as an industrial production method.

[0004]

Means for Solving the Problems As a result of intensive studies for solving the above problems, the present inventors have found that cyanopyridines having a halogen atom at the α-position are contacted with each other in the presence of a Raney nickel catalyst having specific properties. The present inventors have found that aminomethylpyridines having a halogen atom at the α-position can be obtained in high yield by reduction, and have reached the present invention.

That is, the gist of the present invention is that cyanopyridines having a halogen atom at the α-position have a sedimentation rate of 1.0 cm.
/ Sec or less and the hydrogenated phenol activity is 10
A method for producing aminomethylpyridines having a halogen atom at the α-position is characterized in that catalytic reduction is carried out in the presence of a Raney nickel catalyst having a hydrogen content of 00H ₂ ml / gNi / hr or less.

The preferred specific embodiments of the present invention will be described below. Aminomethylpyridines having a halogen atom at the α-position have a specific property of usually 0.05 to 1 part by weight per 1 part by weight of the cyanopyridine in a solvent containing cyanopyridine having a halogen atom at the α-position. In the presence of the Raney nickel catalyst, usually in the temperature range of -20 to 150 ° C, preferably in the temperature range of 10 to 60 ° C for suppressing dehalogenation and dimerization, and usually at a hydrogen pressure of 1 to 1
Hydrogen can be added at a pressure of 00 atm, preferably 1 to 10 atm to carry out catalytic reduction. After completion of the reaction, the Raney nickel catalyst is filtered off from the reaction solution, the solvent is distilled off, and the residue is separated by distillation. At this time, it is common to continuously supply the amount of hydrogen consumed by the reaction and maintain the hydrogen pressure. The reaction may be terminated when the hydrogen has been consumed.

Further, in the present invention, when ammonia is allowed to coexist in the reaction system for catalytic reduction, dimerization of aminomethylpyridines having a halogen atom at the α-position can be suppressed. The amount of ammonia used is 10 to 200% by weight with respect to the cyanopyridines having a halogen atom at the α-position, but in the range of 20 to 100% by weight from the viewpoint of reaction rate and suppression of dimerization of aminomethylpyridines. 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 / s, considering the yield of aminomethylpyridine.
ec or less, more preferably 0.6 cm / sec or less, and considering the yield of aminomethylpyridine, the hydrogenated phenol activity is 1000 H ₂ ml / gNi / hr or less, preferably 600 H ₂ ml / gNi / hr. The following is used, and more preferably, the Al content is 3 to 8 wt% with respect to the Ni content in the Raney nickel catalyst.

The above settling speed is 50 g of the catalyst in a 500 ml graduated cylinder (internal diameter 5 cm, cylindrical type) with a stopper.
(Dry weight) is made up to 500 ml with pure water (that is, 25.5 cm from the bottom of the graduated cylinder), then shaken until the contents become uniform and then left standing, and the start of standing is 0 hours (sec). Then, the time (sedimentation time (sec)) until the distance between the water surface and the catalyst layer surface reaches 15.0 cm after the content in the cinder is separated is measured and calculated using the following calculation formula.

Settling velocity (cm / sec) = 15.0 (c
m) / precipitation time (sec) For hydrogenated phenol activity, about 1 g (dry weight 0.7 g) of a slurry of Raney nickel catalyst washed with ethanol was added to 100 ml of a mixed solution of phenol and cyclohexanol (weight ratio 7: 3). After adding hydrogen for 30 minutes at room temperature and 1 atm to measure the amount of absorbed hydrogen, the amount of Ni in the catalyst is measured and calculated using the following formula.

Hydrogenated phenol activity (H ₂ ml / g Ni
/ Hr) = a × 12 × 273 ÷ (b × (273 + t)) a: average hydrogen absorption amount per 5 minutes in 30 minutes (ml) b: Ni content of catalyst used in reaction (g) t: Room temperature (° C.) The hydrogenated phenol activity is used as an index representing the hydrogenation activity of Raney nickel.

The Raney nickel catalyst used in the present invention has a particle size distribution of 40 μm or less of 90% or more and 20 μm or less.
m or less is 50% or more, preferably 40 μm or less is 95%
From the above, and from Raney nickel alloy adjusted to 20% or less to 70% or more, an aqueous sodium hydroxide solution is used, and the temperature is in the range of -20 ° C to 200 ° C for 30 minutes to 15 minutes.
It can be manufactured by reacting for a period of time to appropriately elute aluminum and then appropriately washing.

The solvent used in the present invention is not particularly limited as long as it is an inert solvent for the reduction reaction.
Examples thereof include alcohols such as ethanol and butanol, hydrocarbons such as benzene, toluene and cyclohexane, cyclic ethers such as tetrahydrofuran and dioxane, and alcohol solvents are particularly preferable from the viewpoint of the yield of aminomethylpyridine. The amount of the solvent used is 1 to 25 times (weight), preferably 10 to 15 times the amount of the aminomethylpyridines having a halogen atom 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 (I)

[0015]

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
Group, C ₁~ C₈Of the alkoxy or aryl groups of
However, X represents a halogen atom. ). In the above formula
And, as the halogen atom, fluorine atom, chlorine atom, odor
An elementary atom, an iodine atom and the like can be mentioned. C₁~ C₈The archi
Groups include methyl, ethyl, propyl, and isop
Ropyl group, butyl group, isobutyl group, sec-butyl
Group, tert-butyl group, pentyl group, neopentyl group
Group, tert-pentyl group, hexyl group, heptyl group,
An octyl group etc. are mentioned. C₁~ C₈With the alkoxy group of
Is a methoxy group, ethoxy group, propoxy group, iso
Propoxy group, butoxy group, isobutoxy group, sec-
Butoxy group, tert-butoxy group, pentyloxy
Group, neopentyloxy group, tert-pentyloxy
Group, hexyloxy group, heptyloxy group, octyloxy group
A xy group etc. are mentioned. Phenyl as an aryl group
Group, tolyl group, naphthyl group and the like.

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 (197).
It can be easily obtained by 1)).

[0019]

EXAMPLES The present invention will now be described in more detail with reference to examples, but the present invention is not limited to the following examples as long as the gist thereof is not exceeded. Example 1 100 g of 2-chloro-5-cyanopyridine, 950 g of ethanol, Raney nickel (manufactured by Nikko Rica Ltd.) 25
g, and 180 g of 28% ammonia water were charged, and the reaction was carried out for 7 hours while vigorously stirring at 20 ° C. while maintaining hydrogen at 1 atm. After completion of the reaction, the catalyst was filtered off from the reaction solution and distilled to obtain 2-chloro-5-aminomethylpyridine in a yield of 89%.

The Raney nickel catalyst (manufactured by Nikko Rica Co., Ltd.) used in this example has the following properties. Sedimentation rate: 0.45 cm / sec Hydrogenated phenol activity: 420 (H ₂ ml / g Ni
/ Hr) Al content (Al / Ni): 5.2% Particle size distribution (40 μm or less): 97% (20 μm or less): 73% BET-total surface area: 80 m ² / gNi The particle size distribution is a laser diffraction confusion formula. It measured with the particle size distribution measuring device (HORIBA, LA-700).

Examples 2 to 5 Tests were conducted in the same manner as in Example 1 using the catalysts having the properties shown in Table 1. Table 1 shows the yield of the obtained 2-chloro-5-aminomethylpyridine. Comparative Example 1 Using a catalyst having the properties shown in Table 1, a test was conducted in the same manner as in Example 1. Table 1 shows the yield of the obtained 2-chloro-5-aminomethylpyridine.

[0022]

[Table 1]

[0023]

INDUSTRIAL APPLICABILITY According to the present invention, an amino acid having a halogen atom at the α-position can be obtained by using a Raney nickel catalyst having specific physical properties in the catalytic reduction of cyanopyridines having a halogen atom at the α-position. Methylpyridines can be produced in high yield.

Claims (6)

[Claims] 1. A cyanopyridine having a halogen atom at the α-position has a sedimentation rate of 1.0 cm / sec or less,
And hydrogenated phenol activity is 1000 H ₂ ml / g Ni
A method for producing aminomethylpyridines having a halogen atom at the α-position, which comprises catalytically reducing in the presence of a Raney nickel catalyst having an amount of / hr or less. 2. The method according to claim 1, wherein the Raney nickel catalyst has a hydrogenated phenol activity of 600 H ₂ ml / gNi / hr or less. 3. The Raney nickel catalyst has a sedimentation rate of 0.8.
The method according to claim 1 or 2, wherein the method is cm / sec or less. 4. The Raney nickel catalyst has a sedimentation rate of 0.6.
The method according to claim 1 or 2, wherein the method is cm / sec or less. 5. The content of Al in the Raney nickel catalyst is
It is 3-8 wt% with respect to Ni content, The method in any one of Claims 1-4 characterized by the above-mentioned. 6. The method according to claim 1, wherein the cyanopyridine having a halogen atom at the α-position is 2-chloro-5-cyanopyridine.