JPH05320132A - Production of 2-chloro-5-chloromethylpyridine and/or 2-chloro-5-dichloromethlpyridine - Google Patents

Abstract

PURPOSE:To produce 2-chloro-5-(di)chloromethylpyridine useful as an intermedi ate of agricultural and medical drugs, etc., with industrial advantage merely by reducing 2-chloro-5-trichloromethylpyridine which can readily be obtained from 3-picoline through one stage. CONSTITUTION:2-Chloro-5-trichloromethylpyridine readily obtained, e.g. by gas phase chlorination of 3-picoline using chlorine is reduced (Catalytic reduction is especially preferable) by zinc and an acid (Hydrochloric acid is especially preferable) or an alkali (NaOH is especially preferable) to obtain 2-chloro-5- chloromethylpyridine and/or 2-chloro-5-dichloromethylpyridine. The resultant 2-chloro-5-dichloromethylpyridine is further reduced to obtain 2-chloro-5- chloromethylpyridine. In the case of a catalytic reduction, a Raney catalyst is preferably used as the catalyst. As a general tendency, the main product is 2-chlore-5-chloromethylpyridine if Raney nickel is used as the catalyst. In case Raney cobalt, etc., is used, 2-chloro-5-dichloromethylpyridine is obtained as the main product.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing 2-chloro-5-chloromethylpyridine and / or 2-chloro-5-dichloromethylpyridine. More specifically, 2
-Chloro-5-trichloromethylpyridine is reduced to 2
-Method for producing chloro-5-chloromethylpyridine and / or 2-chloro-5-dichloromethylpyridine, and reduction of 2-chloro-5-dichloromethylpyridine to produce 2-chloro-5-chloromethylpyridine It is about how to do. 2-Chloro-5-chloromethylpyridine and 2-chloro-5-dichloromethylpyridine are compounds useful as intermediates for medicines and agricultural chemicals.

[0002]

2. Description of the Related Art As a method for producing 2-chloro-5-chloromethylpyridine and / or 2-chloro-5-dichloromethylpyridine, various methods have hitherto been proposed, but all are industrial production methods. Is not as satisfactory. Taking 2-chloro-5-chloromethylpyridine as an example, the following methods are known. A method of directly chlorinating 2-chloro-5-methylpyridine with chlorine to obtain 2-chloro-5-chloromethylpyridine (JP-A-63-68565). A method of chlorinating 2-chloro-5-hydroxymethylpyridine with an appropriate chlorinating agent to obtain 2-chloro-5-chloromethylpyridine (JP-A-63-51387 and JP-A-2-171). A method for obtaining 2-chloro-5-chloromethylpyridine by reacting 2-methoxy-5-methoxymethylpyridine with phosphorus oxychloride (JP-A-2-292262).
Publication).

[0003]

In all of these conventional methods, the pyridine derivative as a raw material requires a plurality of steps in production from 3-picoline which is industrially mass-produced,
It is difficult to say that the conventional method is industrially preferable. That is, 2-chloro-5-methylpyridine in the method of 2 is obtained by reacting 3-picoline with sodamide at high pressure.
-Amino-5-methylpyridine, which is obtained by diazo decomposition in the presence of hydrochloric acid. The 2-chloro-5-hydroxymethylpyridine in the method of 1 is an ester of 6-chloronicotinic acid produced in several steps from 3-picoline, and this ester is an expensive reducing agent such as sodium borohydride and lithium aluminum hydride. Or obtained by reducing 2-chloro-5-cyanopyridine produced from 3-picoline in several steps by hydrogenation in the presence of an acid. 2-methoxy-5-methoxymethylpyridine in the method of 1) is obtained by liquid-phase chlorinating 3-picoline in the presence of a large amount of expensive radical generator to 3-dichloromethylpyridine, which is reacted with sodium methylate. can get.

Further, since sodaamide is used at a high pressure in the raw material production step of the above method, there is a drawback that the production risk is great. There is a drawback in that an expensive reducing agent must be used in the raw material manufacturing process of the method of (1). The raw material manufacturing process of the method (1) has a drawback that a large amount of expensive radical generator must be used.

[0005]

DISCLOSURE OF THE INVENTION The inventors of the present invention have conducted extensive studies to solve the above-mentioned drawbacks of the conventional method, and as a result, 2-chloro-5- which can be produced from 3-picoline in one step.
Trichloromethylpyridine can be reduced to 2-chloro-
5-chloromethylpyridine and / or 2-chloro-5-
It was found that dichloromethylpyridine can be easily obtained, and further, that 2-chloro-5-chloromethylpyridine can be easily obtained by reducing 2-chloro-5-dichloromethylpyridine, and the present invention was completed. Came to do.

That is, the present invention is characterized by reducing 2-chloro-5-trichloromethylpyridine.
-Chloro-5-chloromethylpyridine and / or a method for producing 2-chloro-5-dichloromethylpyridine, and 2-chloro-5-chloromethylpyridine characterized by reducing 2-chloro-5-dichloromethylpyridine The present invention relates to a method for producing pyridine.

2-chloro-5, which is a raw material for the method of the present invention
Trichloromethylpyridine is described in, for example, JP-A-54-11.
It can be obtained in one step by vapor-phase chlorinating 3-picoline with chlorine by the method described in JP-A-5381 or JP-A-55-43017.

Both 2-chloro-5-trichloromethylpyridine and 2-chloro-5-dichloromethylpyridine are collectively referred to as 2-chloro-5-tri (di) chloromethylpyridine. In the method of the present invention, as a means for reducing 2-chloro-5-tri (di) chloromethylpyridine, reduction using a metal such as zinc and an acid or alkali, catalytic reduction, electrolytic reduction and the like can be adopted.
Among these, reduction and catalytic reduction using zinc and an acid or alkali are preferable from the viewpoint of yield and selectivity, and the former is more preferable.

Examples of the acid include inorganic acids such as hydrochloric acid, sulfuric acid and acetic acid, and organic acids. Of these, hydrochloric acid is most preferable. The amount of acid may be 1 equivalent or more per mol of zinc. Examples of the alkali include sodium hydroxide and potassium hydroxide. The amount of alkali may be 1 equivalent or more per mol of zinc.

When 2-chloro-5-trichloromethylpyridine is reduced with zinc and an acid or an alkali, 2-chloro-5-chloromethylpyridine and 2-chloro-5-dichloromethylpyridine are used depending on the amount of zinc used. The generation ratio of changes. That is, the amount of zinc used is 2-
The amount of chloro-5-trichloromethylpyridine is preferably 1.7 to 2.3 mol times, particularly preferably 1.8 to 2.1 mol times when used in combination with an acid, and 1.8 to 2.1 times when used in combination with an alkali. 2-chloro-5 when the molar ratio is 2.2
-Chloromethylpyridine is mainly produced. When the amount of zinc used is preferably 0.8 to 1.2 times the molar amount of 2-chloro-5-trichloromethylpyridine, 2-
Chloro-5-dichloromethylpyridine is mainly produced.

When the starting material is 2-chloro-5-dichloromethylpyridine, the amount of zinc used is preferably 0.7 to 1.3 times the molar amount of this starting material, particularly preferably 0.8 to It is 1.1 times the molar amount.

As described above, when the starting material is 2-chloro-5-trichloromethylpyridine, 2-chloro-5-chloromethylpyridine and 2-chloro-5-dichloromethylpyridine are produced depending on the amount of zinc used. Since 2-chloro-5-dichloromethylpyridine can be prepared by changing the ratio and 2-chloro-5-dichloromethylpyridine can be produced, 2-chloro-5-trichloromethylpyridine is 2-Chloro-5-dichloromethylpyridine is mainly produced by reducing with 0.7 to 1.3 times mol of zinc, and then 2-chloro-5-dichloromethylpyridine is reduced to give 2-chloro-5- It is also possible to convert it to chloromethylpyridine.

When catalytic reduction is carried out, examples of the catalyst include Raney catalysts such as Raney nickel and Raney cobalt, precious metal catalysts such as ruthenium carbon, and the like. Among them, Raney catalysts are preferable from the viewpoint of yield and the like. Two
In the case of catalytic reduction of -chloro-5-trichloromethylpyridine, when Raney nickel is used as a catalyst, 2-chloro-5-chloromethylpyridine tends to be the main product, and when Raney cobalt or ruthenium carbon is used, 2- Chloro-5-dichloromethylpyridine tends to be the major product. The amount of the catalyst is preferably 1 to 20% by weight based on 2-chloro-5-tri (di) chloromethylpyridine. There is no problem if the hydrogen pressure of the catalytic reduction is atmospheric pressure or more, but 10 to 40 atm is desirable from the viewpoint of reaction rate and equipment. A deoxidizing agent is usually used for catalytic reduction of 2-chloro-5-tri (di) chloromethylpyridine, and a tertiary amine such as triethylamine is desirable as the deoxidizing agent.

In the case of catalytic reduction of 2-chloro-5-trichloromethylpyridine, the main product 2-chloro-5-dichloromethylpyridine obtained by selecting the type of catalyst as described above is reduced. It is also possible to lead to 2-chloro-5-chloromethylpyridine.

The reduction temperature in the method of the present invention is usually from the freezing point to the boiling point of the solvent used, an extremely low temperature is meaningless, and an extremely high temperature is 2-chloro-
5-tri (di) chloromethylpyridine and 2-chloro-
It is not preferable because it causes decomposition of 5-chloromethylpyridine. The temperature is preferably in the temperature range of 0 ° C to 50 ° C.

The solvent which can be used in the method of the present invention is not particularly limited as long as it is a solvent which is not easily subjected to reduction, but in the case of reduction using zinc and an acid, mixing with an acid poses a problem. Lower alcohols such as isopropanol or lower ethers such as dioxane and methyl cellosolve are preferable.

2-Chloro-5-chloromethylpyridine and 2-chloro-5-dichloromethylpyridine are obtained by distilling a crude product obtained by removing a solvent, a catalyst, an inorganic substance and the like from a reaction liquid after the reduction by a conventional method. Alternatively, it can be isolated and purified by recrystallization.

[0018]

EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to these examples. Example 1 23.1 g of 2-chloro-5-trichloromethylpyridine
Is dissolved in 100 g of isopropanol, and metallic zinc powder 1
3.7 g was added and stirred. While maintaining the temperature at 12 ° C. or lower, 55 g of 20% hydrochloric acid was gradually added dropwise over 2 hours. After completion of the dropping, the reaction solution was concentrated and dichloroethane 10 was added.
0 g was added, 100 g of water was added, and the mixture was stirred. The mixture is neutralized to pH 5 with sodium hydroxide, the oil layer is removed,
Concentration gave 15.7 g of a tan oil. Gas chromatographic analysis of this oil gave 2-
Chloro-5-chloromethylpyridine and 2-chloro-5-
Dichloromethylpyridine was contained in yields of 68% and 9%, respectively.

Example 2 23.1 g of 2-chloro-5-trichloromethylpyridine
Was dissolved in 100 g of isopropanol, 6.8 g of metallic zinc powder was added, and the mixture was stirred. 20 g of 20% hydrochloric acid was gradually added dropwise over 2 hours while maintaining the temperature at 12 ° C or lower. After the dropping was completed, the same operation as in Example 1 was carried out to obtain 19.7 g of a single brown oily substance. Gas chromatographic analysis of this oil revealed that it contained 2-chloro-5-dichloromethylpyridine and 2-chloro-5-chloromethylpyridine in 74% and 13% yields, respectively.

Example 3 2-Chloro-5-dichloromethylpyridine (19.7 g) was dissolved in 100 g of isopropanol to prepare metallic zinc powder 6.
8 g was added and stirred. While keeping the temperature below 12 ℃,
20 g of 20% hydrochloric acid was gradually added dropwise over 2 hours. After the dropping was completed, the same operation as in Example 1 was carried out to obtain 16.1 g of a single brown oily substance. Gas chromatographic analysis of this oil revealed that it contained 2-chloro-5-chloromethylpyridine in a yield of 72.5%.

Example 4 23.1 g of 2-chloro-5-trichloromethylpyridine
Is dissolved in 100 g of isopropanol, and metallic zinc powder 1
3.7 g was added and stirred. While maintaining the temperature at 12 ° C. or lower, 40.5 g of a 48% aqueous sodium hydroxide solution was gradually added dropwise over 2 hours. After completion of dropping, the reaction solution was concentrated, 100 g of dichloroethane was added, 100 g of water was added, and the mixture was stirred. The oil layer is removed and concentrated to give a tan oil 1
2.3 g were obtained. Gas chromatographic analysis of this oil revealed that it contained 2-chloro-5-chloromethylpyridine and 2-chloro-5-dichloromethylpyridine in yields of 48% and 20%, respectively.

Example 5 11.5 g of 2-chloro-5-trichloromethylpyridine
Was dissolved in 50 g of isopropanol and placed in a 100 ml autoclave. Add 1 g of Raney nickel,
Two equivalents of triethylamine were added, and catalytic reduction was carried out at 50 ° C. and 40 atm for 2 hours. After the reaction, insoluble matter was removed by filtration, and the filtrate was concentrated. 50 g of dichloroethane was added to the obtained concentrated residue, 50 g of water was added, and the mixture was stirred. The mixture was neutralized to pH 7 with sodium hydroxide, the oil layer was removed, and concentrated to obtain 8.7 g of a single brown oily substance.
Gas chromatographic analysis of this oil gave 2-chloro-5-chloromethylpyridine and 2-chloro-
5-dichloromethylpyridine is 38% and 25% respectively
Was included in the yield of.

Example 6 The procedure of Example 5 was repeated except that Raney nickel was replaced with Raney cobalt to obtain 8.3 g of a single brown oily substance.
Gas chromatographic analysis of this oil gave 2-chloro-5-chloromethylpyridine and 2-chloro-
5-dichloromethylpyridine is 2.4% and 63%, respectively.
% Yield was included.

[0024]

Industrial Applicability According to the method of the present invention, 2-chloro-5-chloromethylpyridine and 2-chloro-5-trichloromethylpyridine, which can be produced in one step from industrially mass-produced 3-picoline, can be easily prepared. / Or 2-chloro-
Since 2-dichloromethylpyridine can be produced, 2-chloro-5, which is industrially advantageous as compared with the conventional method,
A method for producing -chloromethylpyridine and / or 2-chloro-5-dichloromethylpyridine can be provided. Again 2
2-chloro-5-dichloromethyl pyridine easily
Chloro-5-chloromethylpyridine can be prepared.

Claims (10)

[Claims] 1. A method for producing 2-chloro-5-chloromethylpyridine and / or 2-chloro-5-dichloromethylpyridine, which comprises reducing 2-chloro-5-trichloromethylpyridine. 2. The production method according to claim 1, wherein the reduction is performed with zinc and an acid or an alkali. 3. The method according to claim 2, wherein the acid is hydrochloric acid. 4. The method according to claim 2, wherein the alkali is sodium hydroxide. 5. The production method according to claim 1, wherein the reduction is carried out by catalytic reduction. 6. A method for producing 2-chloro-5-chloromethylpyridine, which comprises reducing 2-chloro-5-dichloromethylpyridine. 7. The method according to claim 6, wherein the reduction is performed with zinc and an acid or an alkali. 8. The method according to claim 7, wherein the acid is hydrochloric acid. 9. The method according to claim 7, wherein the alkali is sodium hydroxide. 10. The production method according to claim 6, wherein the reduction is carried out by catalytic reduction.