JPH06279410A - Production of 2-chloro-5-aminomethylpyridines - Google Patents
Production of 2-chloro-5-aminomethylpyridinesInfo
- Publication number
- JPH06279410A JPH06279410A JP5352601A JP35260193A JPH06279410A JP H06279410 A JPH06279410 A JP H06279410A JP 5352601 A JP5352601 A JP 5352601A JP 35260193 A JP35260193 A JP 35260193A JP H06279410 A JPH06279410 A JP H06279410A
- Authority
- JP
- Japan
- Prior art keywords
- chloro
- hydrogen
- trichloromethylpyridine
- reaction
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は２−クロロ−５−アミノ
メチルピリジン類の新規な製造方法に関する。更に詳し
くは、２−クロロ−５−トリクロロメチルピリジンとア
ミン類と水素を水素化触媒の存在下で反応させることに
よる２−クロロ−５−アミノメチルピリジン類の新規な
製造方法に関する。２−クロロ−５−アミノメチルピリ
ジン類は医薬及び農薬の合成原料として有用な化合物で
ある。FIELD OF THE INVENTION The present invention relates to a novel method for producing 2-chloro-5-aminomethylpyridines. More specifically, it relates to a novel method for producing 2-chloro-5-aminomethylpyridines by reacting 2-chloro-5-trichloromethylpyridine with amines and hydrogen in the presence of a hydrogenation catalyst. 2-Chloro-5-aminomethylpyridines are compounds useful as synthetic raw materials for medicines and agricultural chemicals.
【０００２】[0002]
【従来の技術】従来２−クロロ−５−アミノメチルピリ
ジン類の製造方法としては、例えば、２−クロロ−５−
モノクロロメチルピリジンをアミン類と反応させる方法
等が知られている（特開平２−１７１号等）。2. Description of the Related Art Conventional methods for producing 2-chloro-5-aminomethylpyridines include, for example, 2-chloro-5-
A method of reacting monochloromethylpyridine with amines and the like are known (JP-A-2-171 etc.).
【０００３】[0003]
【発明が解決しようとする課題】しかしながらこの方法
に用いられる原料の２−クロロ−５−モノクロロメチル
ピリジンは、高圧で３−メチルピリジンとソーダアミド
を反応させてアミノ化して２−アミノ−５−メチルピリ
ジンとし、これをジアゾ分解、クロロ化し、そして得ら
れた２−クロロ−５−メチルピリジンをクロロ化して製
造される。このように２−クロロ−５−モノクロロメチ
ルピリジンを得るには、工業的入手が容易な３−メチル
ピリジンから出発した場合、長い工程を必要とする。ま
た２−クロロ−５−モノクロロメチルピリジンは皮膚刺
激性の強い化合物である。これらのことより２−クロロ
−５−モノクロロメチルピリジンを原料とする従来方法
は工業的に有利な方法とは言い難い。However, the starting material 2-chloro-5-monochloromethylpyridine used in this method is amination by reacting 3-methylpyridine with sodaamide at high pressure to give 2-amino-5-methyl. Pyridine is prepared by diazotization, chlorination, and chlorination of the resulting 2-chloro-5-methylpyridine. Thus, obtaining 2-chloro-5-monochloromethylpyridine requires a long process when starting from 3-methylpyridine, which is industrially readily available. Further, 2-chloro-5-monochloromethylpyridine is a compound having a strong skin irritation. From these things, it is hard to say that the conventional method using 2-chloro-5-monochloromethylpyridine as a raw material is industrially advantageous.
【０００４】[0004]
【課題を解決するための手段】本発明者等は、これらの
欠点を有さない製造方法を見出すべく検討を重ねた結
果、３−メチルピリジンからクロロ化によって１工程で
製造することのできる２−クロロ−５−トリクロロメチ
ルピリジンを出発原料として、これとアミン類と水素を
水素化触媒の存在下で反応させるだけで、２−クロロ−
５−アミノメチルピリジン類が製造できることを見出し
本発明を完成した。Means for Solving the Problems As a result of repeated studies to find a production method which does not have these drawbacks, the present inventors can produce 3-methylpyridine in one step by chlorination. Starting from -chloro-5-trichloromethylpyridine as a starting material, 2-chloro-trichloromethylpyridine is reacted with amines and hydrogen in the presence of a hydrogenation catalyst.
The present invention has been completed by discovering that 5-aminomethylpyridines can be produced.
【０００５】すなわち、本発明は、２−クロロ−５−ト
リクロロメチルピリジンと一般式（１）：That is, the present invention relates to 2-chloro-5-trichloromethylpyridine and the general formula (1):
【化３】 ［式中、Ｒ1は水素原子、アルキル基又はアミノアルキ
ル基を示す。Ｒ2は水素原子又はアルキル基を示す。］
で表されるアミン類（以下、アミン類（１）という）と
水素を、水素化触媒の存在下で、反応させることを特徴
とする一般式（２）：[Chemical 3] [In the formula, R 1 represents a hydrogen atom, an alkyl group or an aminoalkyl group. R 2 represents a hydrogen atom or an alkyl group. ]
General formula (2) characterized by reacting amines represented by (hereinafter, referred to as amines (1)) with hydrogen in the presence of a hydrogenation catalyst:
【化４】 ［式中、Ｒ1及びＲ2は前記に同じ。］で表される２−ク
ロロ−５−アミノメチルピリジン類（以下、２−クロロ
−５−アミノメチルピリジン類（２）という）の製造方
法に関するものである。[Chemical 4] [In the formula, R 1 and R 2 are the same as defined above. ] It is related with the manufacturing method of 2-chloro-5-aminomethyl pyridines (henceforth 2-chloro-5-aminomethyl pyridines (2)) represented by.
【０００６】一般式（１）及び（２）においてＲ1及び
Ｒ2で示されるアルキル基としては、メチル基、エチル
基、プロピル基、ブチル基等が挙げられる。またＲ1で
示されるアミノアルキル基としては、２−アミノエチル
基、２−アミノプロピル基、３−アミノプロピル基、２
−アミノブチル基、３−アミノブチル基、４−アミノブ
チル基等が挙げられる。Examples of the alkyl group represented by R 1 and R 2 in the general formulas (1) and (2) include a methyl group, an ethyl group, a propyl group and a butyl group. The aminoalkyl group represented by R 1 includes 2-aminoethyl group, 2-aminopropyl group, 3-aminopropyl group, 2
-Aminobutyl group, 3-aminobutyl group, 4-aminobutyl group and the like can be mentioned.
【０００７】アミン類（１）としては、アンモニア、メ
チルアミン、エチルアミン等のモノアルキルアミン、エ
チレンジアミン、１，２−ジアミノプロパン、１，４−
ジアミノブタン等のジアミン類、及びジメチルアミン、
ジエチルアミン等のジアルキルアミン類等が挙げられ
る。またこれらのアミン類は、副生物の生成を抑えるた
め、適当な保護基を付けて反応することも可能である。
アミン類（１）の使用量は２−クロロ−５−トリクロロ
メチルピリジンに対して１〜２０倍モル、好ましくは２
〜１０倍モルである。As amines (1), ammonia, monoalkylamines such as methylamine and ethylamine, ethylenediamine, 1,2-diaminopropane, 1,4-
Diamines such as diaminobutane, and dimethylamine,
Dialkylamines such as diethylamine and the like can be mentioned. Further, these amines can be reacted with an appropriate protecting group in order to suppress the production of by-products.
The amount of amines (1) used is 1 to 20 times mol, preferably 2 times, of 2-chloro-5-trichloromethylpyridine.
It is 10 times the molar amount.
【０００８】本発明の方法では、反応によって脱離した
塩素原子が水素と反応して副生成物である塩化水素が生
じる。塩化水素を過剰のアミン類（１）で中和すること
ができるが、塩化水素の中和のために反応系内に３級ア
ミンを共存させることができる。In the method of the present invention, the chlorine atom eliminated by the reaction reacts with hydrogen to produce a by-product hydrogen chloride. Hydrogen chloride can be neutralized with excess amines (1), but a tertiary amine can coexist in the reaction system for neutralizing hydrogen chloride.
【０００９】２−クロロ−５−アミノメチルピリジン類
（２）としては、２−クロロ−５−アミノメチルピリジ
ン、２−クロロ−５−メチルアミノメチルピリジン、２
−クロロ−５−エチルアミノメチルピリジン、２−クロ
ロ−５−（２−アミノエチル）アミノメチルピリジン、
２−クロロ−５−（２−アミノプロピル）アミノメチル
ピリジン、２−クロロ−５−ジメチルアミノメチルピリ
ジン、２−クロロ−５−ジエチルアミノメチルピリジン
等が挙げられる。As 2-chloro-5-aminomethylpyridines (2), 2-chloro-5-aminomethylpyridine, 2-chloro-5-methylaminomethylpyridine, 2
-Chloro-5-ethylaminomethylpyridine, 2-chloro-5- (2-aminoethyl) aminomethylpyridine,
2-chloro-5- (2-aminopropyl) aminomethylpyridine, 2-chloro-5-dimethylaminomethylpyridine, 2-chloro-5-diethylaminomethylpyridine and the like can be mentioned.
【００１０】本発明の方法に使用できる水素化触媒とし
てはラネーニッケル、ラネーコバルト等のラネー触媒、
あるいは、ルテニウムカーボン、ロジウムカーボン、プ
ラチナカーボン等の貴金属触媒が挙げられるが、好まし
くはラネーニッケルである。ラネーニッケルを使用する
と、ピリジン核の２位のクロロ基の水素還元（脱クロロ
化）が生じ難く、実質的に側鎖のトリクロロメチル基の
みが脱クロロ化される。水素化触媒の使用量は２−クロ
ロ−５−トリクロロメチルピリジンに対し１〜５０重量
％、好ましくは５〜２０重量％である。The hydrogenation catalyst that can be used in the method of the present invention includes Raney catalysts such as Raney nickel and Raney cobalt,
Alternatively, a noble metal catalyst such as ruthenium carbon, rhodium carbon or platinum carbon may be used, but Raney nickel is preferable. When Raney nickel is used, hydrogen reduction (dechlorination) of the chloro group at the 2-position of the pyridine nucleus is less likely to occur, and substantially only the side chain trichloromethyl group is dechlorinated. The amount of hydrogenation catalyst used is 1 to 50% by weight, preferably 5 to 20% by weight, based on 2-chloro-5-trichloromethylpyridine.
【００１１】本発明の方法において使用できる溶媒とし
ては、メタノール、エタノール、イソプロパノール等の
アルコール類、水などの極性溶媒、ベンゼン、トルエ
ン、キシレン等の非極性溶媒が挙げられる。溶媒の使用
量は原料である２−クロロ−５−トリクロロメチルピリ
ジンに対して０〜２０重量倍、好ましくは０〜３重量倍
である。Examples of the solvent which can be used in the method of the present invention include alcohols such as methanol, ethanol and isopropanol, polar solvents such as water, and nonpolar solvents such as benzene, toluene and xylene. The amount of the solvent used is 0 to 20 times by weight, preferably 0 to 3 times by weight, relative to 2-chloro-5-trichloromethylpyridine as a raw material.
【００１２】水素圧は常圧〜１００Ｋｇ／ｃｍ2 、好ま
しくは常圧〜３０Ｋｇ／ｃｍ2 であり、反応温度は０〜
１００℃好ましくは１０〜５０℃である。The hydrogen pressure is normal pressure to 100 kg / cm.2 , Preferred
Normal pressure to 30 kg / cm2 And the reaction temperature is 0 to
100 ° C., preferably 10 to 50 ° C.
【００１３】本発明の方法の好ましい実施態様は、まず
反応器にアミン類（１）及び水素化触媒を仕込み、水素
及び２−クロロ−５−トリクロロメチルピリジンを供給
しながら反応を行う。２−クロロ−５−トリクロロメチ
ルピリジン供給終了後、水素の吸収がなくなるまでさら
に水素の導入を続けて反応を完結させる。２−クロロ−
５−トリクロロメチルピリジン供給時の反応温度は、４
０℃以下であるのが好ましい。In a preferred embodiment of the method of the present invention, first, the amines (1) and the hydrogenation catalyst are charged into a reactor, and the reaction is carried out while supplying hydrogen and 2-chloro-5-trichloromethylpyridine. After the completion of the supply of 2-chloro-5-trichloromethylpyridine, the introduction of hydrogen is continued until the absorption of hydrogen disappears to complete the reaction. 2-chloro-
The reaction temperature when supplying 5-trichloromethylpyridine was 4
It is preferably 0 ° C. or lower.
【００１４】この実施態様で反応を行うと、２−クロロ
−５−トリクロロメチルピリジンの分解を抑制すること
ができ、安全に、高収率で２−クロロ−５−アミノメチ
ルピリジン類（２）を製造することができる。When the reaction is carried out in this embodiment, the decomposition of 2-chloro-5-trichloromethylpyridine can be suppressed, and the 2-chloro-5-aminomethylpyridines (2) can be safely and in high yield. Can be manufactured.
【００１５】本発明方法において生成した２−クロロ−
５−アミノメチルピリジン類（２）の単離、精製は、反
応終了後、水素化触媒の濾別、中和、溶媒等の留去を行
った後、水−トルエン系で抽出し、分液後トルエン層を
濃縮、蒸留すること等により容易にできる。2-chloro-produced in the process of the invention
After completion of the reaction, the 5-aminomethylpyridines (2) are isolated and purified by separating the hydrogenation catalyst by filtration, neutralizing, distilling off the solvent, etc., and then extracting with a water-toluene system to perform liquid separation. This can be easily done by concentrating and distilling the subsequent toluene layer.
【００１６】[0016]
【実施例】以下に実施例を示しさらに詳細に本発明を説
明するが、本発明はこれらの実施例に限定されるもので
はない。EXAMPLES The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.
【００１７】実施例１ 容量１２０ｃｃの電磁攪拌式オ−トクレーブに２−クロ
ロ−５−トリクロロメチルピリジン１１．５ｇ、ラネー
ニッケル１．１５ｇ及び７０％エチルアミン水溶液３
２．２ｇを仕込み、水素で１０Ｋｇ／ｃｍ2 に加圧し、
４５℃に昇温した。当該温度を保ちながら水素圧５〜１
２．５Ｋｇ／ｃｍ2 の間で水素の導入を続け反応を行っ
た。水素吸収は水素導入開始後７０分で終了した。反応
終了後オ−トクレーブを室温まで冷却し、反応液から触
媒を濾別した後、濾液を４８％水酸化ナトリウム水溶液
でｐＨ１２．９とし濃縮した。この濃縮物を、水−トル
エン系で２回抽出し、分液後トルエン層を濃縮し、２−
クロロ−５−エチルアミノメチルピリジンを含む濃縮物
８．０ｇを得た。このものをガスクロマトグラフィーに
より分析したところ、２−クロロ−５−エチルアミノメ
チルピリジンの収率は７７％であった。Example 1 A magnetic stirring type autoclave having a capacity of 120 cc was charged with 2-chloro.
Ro-5-trichloromethylpyridine 11.5 g, Raney
1.15 g of nickel and 70% ethylamine aqueous solution 3
Charge 2.2g, 10Kg / cm with hydrogen2 Pressurize to
The temperature was raised to 45 ° C. Hydrogen pressure 5-1 while keeping the temperature
2.5 kg / cm2 Hydrogen is continuously introduced during the reaction
It was Hydrogen absorption was completed 70 minutes after the start of hydrogen introduction. reaction
After completion, cool the autoclave to room temperature and touch it with the reaction solution.
After filtering off the medium, the filtrate is 48% sodium hydroxide aqueous solution.
The pH was adjusted to 12.9 and concentrated. This concentrate is added to water-torr.
It was extracted twice with an ene system, the toluene layer was concentrated after liquid separation, and 2-
Concentrate containing chloro-5-ethylaminomethylpyridine
8.0 g was obtained. This one for gas chromatography
Upon further analysis, 2-chloro-5-ethylaminometh
The yield of tylpyridine was 77%.
【００１８】実施例２ 容量１１９．５ｃｃの電磁攪拌式オ−トクレーブに２−
クロロ−５−トリクロロメチルピリジン１１．５ｇ、エ
タノール２０ｇ、ラネーニッケル１．１５ｇ及び４０％
メチルアミン水溶液２７．２ｇを仕込み、水素で１０Ｋ
ｇ／ｃｍ2 に加圧し、４５℃に昇温した。当該温度を保
ちながら水素圧７〜１３Ｋｇ／ｃｍ2 の間で水素の導入
を続け反応を行った。水素吸収は水素導入開始後９５分
で終了した。反応終了後オートクレーブを室温まで冷却
し、反応液から触媒を濾別した後、濾液を４８％水酸化
ナトリウム水溶液でｐＨ１２．９とし濃縮した。この濃
縮物を水−トルエン系で２回抽出し分液後、トルエン層
を濃縮し２−クロロ−５−メチルアミノメチルピリジン
を含む濃縮物４．９ｇを得た。このものをガスクロマト
グラフィーにより分析したところ、２−クロロ−５−メ
チルアミノメチルピリジンの収率は４５％であった。Example 2 An electromagnetic stirring type autoclave having a capacity of 119.5 cc was used for 2-
11.5 g of chloro-5-trichloromethylpyridine, d
20g Tanol, 1.15g Raney Nickel and 40%
Charge 27.2 g of methylamine aqueous solution, and use hydrogen for 10K.
g / cm2 The pressure was increased to 45 ° C. Keep the temperature
While the hydrogen pressure is 7-13Kg / cm2 Introduction of hydrogen between
The reaction was continued. 95 minutes after starting hydrogen introduction
Ended with. After the reaction is complete, cool the autoclave to room temperature
After filtering the catalyst from the reaction mixture, the filtrate was hydroxylated to 48%.
The mixture was adjusted to pH 12.9 with an aqueous sodium solution and concentrated. This rich
The condensed product was extracted twice with a water-toluene system, and after liquid separation, the toluene layer
Is concentrated to give 2-chloro-5-methylaminomethylpyridine.
4.9 g of a concentrate containing was obtained. This is gas chromatograph
When analyzed by chromatography, 2-chloro-5-me
The yield of tylaminomethylpyridine was 45%.
【００１９】実施例３ 容量１１９．５ｃｃの電磁攪拌式オ−トクレーブに２−
クロロ−５−トリクロロメチルピリジン１１．５ｇ、ラ
ネーニッケル１．１５ｇ、エチレンジアミン２１．０ｇ
及びエタノール２０ｇを仕込み、水素で１０Ｋｇ／ｃｍ
2 に加圧し、４５℃に昇温した。当該温度を保ちながら
水素圧７〜１１．２Ｋｇ／ｃｍ2 の間で水素の導入を続
け反応を行った。水素吸収は水素導入開始後１８０分で
終了した。反応終了後オ−トクレーブを室温まで冷却
し、反応液から触媒を濾別した後、濾液を４８％水酸化
ナトリウム水溶液でｐＨ１３．７とし濃縮した。この濃
縮物をガスクロマトグラフィーにより分析したところ、
２−クロロ−５−（２−アミノエチル）アミノメチルピ
リジンの収率は１０％であった。Example 3 A magnetic stirrer type autoclave having a capacity of 119.5 cc was used.
11.5 g of chloro-5-trichloromethylpyridine, la
Nanickel 1.15g, ethylenediamine 21.0g
And 20 g of ethanol were charged, and hydrogen was used at 10 kg / cm.
2 The pressure was increased to 45 ° C. While maintaining the temperature
Hydrogen pressure 7-11.2Kg / cm2 Continue to introduce hydrogen between
The reaction was carried out. 180 minutes after starting hydrogen introduction
finished. After the reaction was completed, the autoclave was cooled to room temperature.
After filtering the catalyst from the reaction mixture, the filtrate was hydroxylated to 48%.
The solution was adjusted to pH 13.7 with an aqueous sodium solution and concentrated. This rich
When the condensed product was analyzed by gas chromatography,
2-chloro-5- (2-aminoethyl) aminomethylpi
The yield of lysine was 10%.
【００２０】実施例４ 容量３０００ｃｃの電磁撹拌式オートクレーブに４０％
メチルアミン水溶液８１４ｇ、エタノール３１２ｇ及び
ラネーニッケル３５ｇを仕込み、水素で３Ｋｇ／ｃｍ2
に加圧した。反応温度を３０℃以下に保ち、水素を導入
しながら２−クロロ−５−トリクロロメチルピリジンの
５８．８％トルエン溶液５８９ｇを４０分で圧入した。
圧入終了後温度を徐々に４０℃まで昇温し、当該温度を
保ちながら水素の吸収がなくなるまで水素の導入を続け
反応を行った。反応終了後オートクレーブを室温まで冷
却し、触媒を濾過により除いた。この濾液を高速液体ク
ロマトグラフィーで分析したところ、２−クロロ−５−
メチルアミノメチルピリジンの収率は７６％であった。
この濾液を４８％水酸化ナトリウム水溶液で中和して濃
縮した。この濃縮液にトルエンを加え、３５％塩酸で抽
出した。この抽出液を再び４８％水酸化ナトリウム水溶
液で中和し、トルエンで抽出した。トルエン層を濃縮す
ると２−クロロ−５−メチルアミノメチルピリジンが回
収率８０％で得られた。Example 4 40% in an electromagnetic stirring type autoclave having a capacity of 3000 cc
A methylamine aqueous solution (814 g), ethanol (312 g) and Raney nickel (35 g) were charged, and hydrogen was added to 3 kg / cm 2.
Pressurized to. While maintaining the reaction temperature at 30 ° C. or lower, 589 g of a 58.8% toluene solution of 2-chloro-5-trichloromethylpyridine was injected under pressure for 40 minutes while introducing hydrogen.
After completion of the press-fitting, the temperature was gradually raised to 40 ° C., and while the temperature was maintained, hydrogen was continuously introduced until the absorption of hydrogen disappeared and the reaction was carried out. After completion of the reaction, the autoclave was cooled to room temperature and the catalyst was removed by filtration. When this filtrate was analyzed by high performance liquid chromatography, it was found that 2-chloro-5-
The yield of methylaminomethylpyridine was 76%.
The filtrate was neutralized with a 48% aqueous sodium hydroxide solution and concentrated. Toluene was added to this concentrated liquid, and the mixture was extracted with 35% hydrochloric acid. The extract was neutralized again with a 48% aqueous sodium hydroxide solution and extracted with toluene. When the toluene layer was concentrated, 2-chloro-5-methylaminomethylpyridine was obtained with a recovery rate of 80%.
【００２１】実施例５ 容量３０００ｃｃの電磁撹拌式オートクレーブに７０％
エチルアミン水溶液９４５ｇ及びラネーニッケル２４ｇ
を仕込み、水素で３Ｋｇ／ｃｍ2に加圧した。反応温度
を１５℃以下に保ち、水素を導入しながら２−クロロ−
５−トリクロロメチルピリジンの５８．８％トルエン溶
液８２５ｇを３時間で圧入した。圧入終了後温度を徐々
に３５℃まで昇温し、当該温度を保ちながら水素の吸収
がなくなるまで水素の導入を続け反応を行った。反応終
了後オートクレーブを室温まで冷却し、濾過により触媒
を除いた。この濾液を高速液体クロマトグラフィーで分
析したところ、２−クロロ−５−エチルアミノメチルピ
リジンの収率は７８％であった。この濾液を濃縮して水
層と油層を分離し、油層を３５％塩酸で抽出した。この
抽出液を４８％水酸化ナトリウム水溶液で中和し、トル
エンで抽出した。トルエン層を濃縮すると２−クロロ−
５−エチルアミノメチルピリジンが回収率７５％で得ら
れた。Example 5 70% in an electromagnetic stirring type autoclave with a capacity of 3000 cc
Ethylamine aqueous solution 945g and Raney nickel 24g
Was charged and pressurized with hydrogen to 3 Kg / cm 2 . Keeping the reaction temperature at 15 ° C or lower, while introducing hydrogen, 2-chloro-
825 g of a 58.8% toluene solution of 5-trichloromethylpyridine was injected under pressure for 3 hours. After completion of the press-fitting, the temperature was gradually raised to 35 ° C., and while the temperature was maintained, hydrogen was continuously introduced until the absorption of hydrogen disappeared and the reaction was carried out. After completion of the reaction, the autoclave was cooled to room temperature and the catalyst was removed by filtration. When this filtrate was analyzed by high performance liquid chromatography, the yield of 2-chloro-5-ethylaminomethylpyridine was 78%. The filtrate was concentrated to separate an aqueous layer and an oil layer, and the oil layer was extracted with 35% hydrochloric acid. The extract was neutralized with a 48% aqueous sodium hydroxide solution and extracted with toluene. When the toluene layer is concentrated, 2-chloro-
5-Ethylaminomethylpyridine was obtained with a recovery rate of 75%.
【００２２】実施例６ 容量５００ｃｃの電磁撹拌式オートクレーブにエチレン
ジアミン１０５ｇ、エタノール１１５ｇ及びラネーニッ
ケル１１．５ｇを仕込み、水素で３Ｋｇ／ｃｍ2に加圧
した。反応温度を２０℃以下に保ち、水素を導入しなが
ら２−クロロ−５−トリクロロメチルピリジンの５８．
８％トルエン溶液９８ｇを約３時間で圧入した。圧入終
了後温度を徐々に３５℃まで昇温し、当該温度を保ちな
がら水素の吸収がなくなるまで水素の導入を続け反応を
行った。反応終了後オートクレーブを室温まで冷却し、
濾過により触媒及び生成する塩を除いた。この濾液を高
速液体クロマトグラフィーで分析すると、２−クロロ−
５−（２−アミノエチル）アミノメチルピリジンの収率
は６６％であった。Example 6 105 g of ethylenediamine, 115 g of ethanol and 11.5 g of Raney nickel were charged into an electromagnetic stirring type autoclave having a capacity of 500 cc, and pressurized to 3 Kg / cm 2 with hydrogen. While maintaining the reaction temperature at 20 ° C. or lower, while introducing hydrogen, 2-chloro-5-trichloromethylpyridine of 58.
98 g of 8% toluene solution was press-fitted in about 3 hours. After completion of the press-fitting, the temperature was gradually raised to 35 ° C., and while the temperature was maintained, hydrogen was continuously introduced until the absorption of hydrogen disappeared and the reaction was carried out. After the reaction is complete, cool the autoclave to room temperature,
The catalyst and the salt formed were removed by filtration. When this filtrate was analyzed by high performance liquid chromatography, 2-chloro-
The yield of 5- (2-aminoethyl) aminomethylpyridine was 66%.
【００２３】[0023]
【発明の効果】本発明の方法によれば、工業的入手が容
易な３−メチルピリジンから簡便に製造できる２−クロ
ロ−５−トリクロロメチルピリジンを用いてワンポット
で２−クロロ−５−アミノメチルピリジン類（２）を製
造することができるので、３−メチルピリジンから出発
した場合、従来方法に比べて極めて短い工程で２−クロ
ロ−５−アミノメチルピリジン類（２）を製造すること
ができる。また、本発明の方法は、皮膚刺激性の強い２
−クロロ−５−モノクロロメチルピリジンを取り扱う必
要がないので、安全性の面でも優れた方法である。INDUSTRIAL APPLICABILITY According to the method of the present invention, 2-chloro-5-aminomethylpyridine can be produced in one pot from 2-chloro-5-trichloromethylpyridine which can be easily produced from 3-methylpyridine which is industrially available. Since pyridines (2) can be produced, when starting from 3-methylpyridine, 2-chloro-5-aminomethylpyridines (2) can be produced in an extremely short step as compared with the conventional method. . In addition, the method of the present invention has a strong skin irritation.
Since it is not necessary to handle -chloro-5-monochloromethylpyridine, it is an excellent method in terms of safety.
Claims (4)
ジンと一般式（１）： 【化１】 ［式中、Ｒ1は水素原子、アルキル基又はアミノアルキ
ル基を示す。Ｒ2は水素原子又はアルキル基を示す。］
で表されるアミン類と水素を、水素化触媒の存在下で、
反応させることを特徴とする一般式（２）： 【化２】 ［式中、Ｒ1及びＲ2は前記に同じ。］で表される２−ク
ロロ−５−アミノメチルピリジン類の製造方法。1. 2-Chloro-5-trichloromethylpyridine and general formula (1): [In the formula, R 1 represents a hydrogen atom, an alkyl group or an aminoalkyl group. R 2 represents a hydrogen atom or an alkyl group. ]
In the presence of a hydrogenation catalyst, the amines and hydrogen represented by
General formula (2) characterized by reacting: [In the formula, R 1 and R 2 are the same as defined above. ] The manufacturing method of 2-chloro-5-aminomethyl pyridine represented by these.
項１記載の方法。2. The method according to claim 1, wherein the hydrogenation catalyst is Raney nickel.
素及び２−クロロ−５−トリクロロメチルピリジンを供
給しながら反応させることを特徴とする請求項１又は２
記載の方法。3. The amine represented by the general formula (1) is reacted while supplying hydrogen and 2-chloro-5-trichloromethylpyridine.
The method described.
求項３記載の方法。4. The method according to claim 3, wherein the reaction temperature at the time of supply is 40 ° C. or lower.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5352601A JPH06279410A (en) | 1993-02-01 | 1993-12-28 | Production of 2-chloro-5-aminomethylpyridines |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3751893 | 1993-02-01 | ||
| JP5-37518 | 1993-02-01 | ||
| JP5352601A JPH06279410A (en) | 1993-02-01 | 1993-12-28 | Production of 2-chloro-5-aminomethylpyridines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH06279410A true JPH06279410A (en) | 1994-10-04 |
Family
ID=26376639
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5352601A Pending JPH06279410A (en) | 1993-02-01 | 1993-12-28 | Production of 2-chloro-5-aminomethylpyridines |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH06279410A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997009312A1 (en) * | 1995-09-08 | 1997-03-13 | Nippon Soda Co., Ltd. | Process for producing 3-(aminomethyl)-6-chloropyridines |
-
1993
- 1993-12-28 JP JP5352601A patent/JPH06279410A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997009312A1 (en) * | 1995-09-08 | 1997-03-13 | Nippon Soda Co., Ltd. | Process for producing 3-(aminomethyl)-6-chloropyridines |
| US5744608A (en) * | 1995-09-08 | 1998-04-28 | Nippon Soda Co., Ltd. | Method for manufacturing 3-(aminomethyl)-6-chloropyridines |
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