JPH09176122A - Production of 6-bromonicotinic acid - Google Patents
Production of 6-bromonicotinic acidInfo
- Publication number
- JPH09176122A JPH09176122A JP33678895A JP33678895A JPH09176122A JP H09176122 A JPH09176122 A JP H09176122A JP 33678895 A JP33678895 A JP 33678895A JP 33678895 A JP33678895 A JP 33678895A JP H09176122 A JPH09176122 A JP H09176122A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- cyano
- bromopyridine
- organic solvent
- bromonicotinic
- 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
Landscapes
- Pyridine Compounds (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、６−ブロモニコチ
ン酸の製造方法に関する。詳しくは、本発明は、特定の
条件下で３−シアノ−６−ブロモピリジンを加水分解す
ることにより６−ブロモニコチン酸を製造する方法に関
する。６−ブロモニコチン酸は、医薬、農薬等の合成原
料として有用な化合物である。TECHNICAL FIELD The present invention relates to a method for producing 6-bromonicotinic acid. Specifically, the present invention relates to a method for producing 6-bromonicotinic acid by hydrolyzing 3-cyano-6-bromopyridine under specific conditions. 6-Bromonicotinic acid is a compound useful as a synthetic raw material for medicines, agricultural chemicals and the like.
【０００２】[0002]
【従来の技術】従来、６−ブロモニコチン酸の製造方法
としては、３−メチル−６−ブロモピリジンを過マンガ
ン酸カリウムで酸化する方法が、例えばジャーナル オ
ヴ オーガニック ケミストリー（Ｊ．Ｏｒｇ．Ｃｈｅ
ｍ．），第１４巻，第５０９頁（１９４２）或いはオー
ストラリアン ジャーナル オヴ ケミストリー（Ａｕ
ｓｔ．Ｊ．Ｃｈｅｍ．），第２４巻，第３７７頁（１９
７１）に開示されている。2. Description of the Related Art Conventionally, as a method for producing 6-bromonicotinic acid, a method of oxidizing 3-methyl-6-bromopyridine with potassium permanganate has been known, for example, Journal of Organic Chemistry (J. Org. Che.
m. ), Vol. 14, p. 509 (1942) or the Australian Journal of Chemistry (Au).
st. J. Chem. ), 24, 377 (19
71).
【０００３】[0003]
【発明が解決しようとする課題】しかしながら、前記の
方法では、目的とする６−ブロモニコチン酸の収率が低
く、また、大量の過マンガン酸カリウムを使用するため
工業的には有利な方法とは言えないという問題点があ
る。本発明の課題は、６−ブロモニコチン酸を工業的に
有利に製造する方法を提供することにある。However, in the above-mentioned method, the yield of the target 6-bromonicotinic acid is low, and since a large amount of potassium permanganate is used, it is an industrially advantageous method. There is a problem that I cannot say. An object of the present invention is to provide a method for industrially advantageously producing 6-bromonicotinic acid.
【０００４】[0004]
【課題を解決するための手段】本発明者等は、上記課題
を解決するため鋭意検討を重ねた結果、３−シアノ−６
−ブロモピリジンを酸水溶液及び非水溶性有機溶媒から
なる二相系混合物中で加水分解することにより、驚くべ
きことにより高収率で６−ブロモニコチン酸が生成する
ことを見出し、本発明を完成するに至った。即ち、本発
明は、下記一般式（Ｉ）で表わされる６−ブロモニコチ
ン酸を製造するに際し、下記一般式（II）で表わされる
３−シアノ−６−ブロモピリジンを酸水溶液及び非水溶
性有機溶媒からなる二相系混合物中で加水分解すること
を特徴とする６−ブロモニコチン酸の製造方法にある。Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems, and as a result, 3-cyano-6
By hydrolyzing -bromopyridine in a two-phase mixture consisting of an aqueous acid solution and a water-insoluble organic solvent, it was surprisingly found that 6-bromonicotinic acid was produced in a high yield, and the present invention was completed. Came to do. That is, in the present invention, in producing 6-bromonicotinic acid represented by the following general formula (I), 3-cyano-6-bromopyridine represented by the following general formula (II) is added to an aqueous acid solution and a water-insoluble organic compound. A method for producing 6-bromonicotinic acid is characterized in that hydrolysis is carried out in a two-phase mixture composed of a solvent.
【０００５】[0005]
【化３】 Embedded image
【０００６】[0006]
【化４】 以下、本発明の方法を詳細に説明する。Embedded image Hereinafter, the method of the present invention will be described in detail.
【０００７】[0007]
（３−シアノ−６−ブロモピリジン）本発明の方法で用
いられる３−シアノ−６−ブロモピリジンは、例えば３
−シアノ−６−ヒドロキシピリジンを臭素化することに
より容易に製造することができる。なお、３−シアノ−
６−ブロモピリジンの純度については特に制限はない
が、通常純度９５％以上のものが用いられる。(3-Cyano-6-bromopyridine) 3-cyano-6-bromopyridine used in the method of the present invention is, for example, 3
It can be easily produced by brominating -cyano-6-hydroxypyridine. In addition, 3-cyano-
The purity of 6-bromopyridine is not particularly limited, but a substance having a purity of 95% or more is usually used.
【０００８】（酸）本発明の方法で用いられる酸類とし
ては、臭化水素酸、硫酸、塩酸等の無機酸類及びｐ−ト
ルエンスルホン酸、酢酸等の有機酸類が挙げられる。こ
の中でも特に臭化水素酸が収率の面から好ましい。酸類
の使用量としては、３−シアノ−６−ブロモピリジン１
モルに対し０．１〜１０倍モルが好ましい。(Acid) Examples of the acids used in the method of the present invention include inorganic acids such as hydrobromic acid, sulfuric acid and hydrochloric acid, and organic acids such as p-toluenesulfonic acid and acetic acid. Of these, hydrobromic acid is particularly preferable in terms of yield. The amount of the acids used is 3-cyano-6-bromopyridine 1
The amount is preferably 0.1 to 10 times the mole.
【０００９】（非水溶性有機溶媒）また、本発明の方法
で用いられる非水溶性有機溶媒としては、トルエン、ベ
ンゼン、クロロベンゼン、ｏ−ジクロロベンゼン等の芳
香族炭化水素、ペンタン、ヘキサン、ヘプタン等の脂肪
族炭化水素、ジエチルエーテル、ジブチルエーテル等の
エーテル類、ジクロロメタン、ジクロロエタン、クロロ
ホルム等のハロゲン化炭化水素等が挙げられる。この中
でも芳香族炭化水素が好ましく、特にトルエンが収率の
面から好ましい。用いる非水溶性有機溶媒の使用量は、
３−シアノ−６−ブロモピリジンに対し１〜２０倍量が
好ましい。なお、酸水溶液と非水溶性有機溶媒との比率
（重量比）は特に限定されないが、通常０．１〜５であ
り、好ましくは０．４〜１である。(Non-water-soluble organic solvent) Further, examples of the non-water-soluble organic solvent used in the method of the present invention include aromatic hydrocarbons such as toluene, benzene, chlorobenzene and o-dichlorobenzene, pentane, hexane and heptane. And aliphatic ethers such as diethyl ether and dibutyl ether, and halogenated hydrocarbons such as dichloromethane, dichloroethane and chloroform. Among these, aromatic hydrocarbons are preferable, and toluene is particularly preferable in terms of yield. The amount of the non-water-soluble organic solvent used is
The amount is preferably 1 to 20 times the amount of 3-cyano-6-bromopyridine. The ratio (weight ratio) of the aqueous acid solution and the water-insoluble organic solvent is not particularly limited, but is usually 0.1 to 5, and preferably 0.4 to 1.
【００１０】（反応方法）３−シアノ−６−ブロモピリ
ジンを加水分解する方法としては、回分式反応でも流通
式反応でもよく、特に制限はされない。回分式反応の場
合、原料の３−シアノ−６−ブロモピリジンを非水溶性
有機溶媒に溶解した溶液に酸水溶液を滴下し、加水分解
反応を行う方法が一般的である。なお、反応中に反応系
に添加された水を共沸により除去しながら反応を行って
もよい。反応温度は特に限定されないが、通常３０〜１
８０℃の範囲、好ましくは５０〜１５０℃の範囲が用い
られる。反応温度が低過ぎる場合には反応に長時間を要
し、一方、反応温度が高過ぎる場合には臭素が加水分解
される等の副反応が起り易く、目的物の収率が低下す
る。反応時間は反応温度或いは酸の使用量により異なる
が、通常０．５〜２０時間、好ましくは１〜１０時間の
範囲が用いられる。また、反応圧力は特に限定されず、
通常は常圧下で反応が行われるが、０．１〜１０ｋｇ／
ｃｍ2 の減圧下ないし加圧下で反応させることもでき
る。上記の反応により生成した目的化合物（Ｉ）は反応
液中に析出して来るので、濾過等により容易に単離する
ことができ、必要に応じて、再結晶等により精製するこ
とができる。(Reaction Method) The method for hydrolyzing 3-cyano-6-bromopyridine may be a batch reaction or a flow reaction, and is not particularly limited. In the case of the batchwise reaction, it is common to carry out a hydrolysis reaction by dropping an aqueous acid solution into a solution of a starting material, 3-cyano-6-bromopyridine, in a water-insoluble organic solvent. The reaction may be carried out while azeotropically removing water added to the reaction system during the reaction. The reaction temperature is not particularly limited, but is usually 30 to 1
A range of 80 ° C, preferably a range of 50 to 150 ° C is used. If the reaction temperature is too low, the reaction takes a long time. On the other hand, if the reaction temperature is too high, a side reaction such as hydrolysis of bromine is likely to occur and the yield of the target product is lowered. The reaction time varies depending on the reaction temperature or the amount of acid used, but is usually 0.5 to 20 hours, preferably 1 to 10 hours. The reaction pressure is not particularly limited,
Usually, the reaction is performed under normal pressure, but 0.1 to 10 kg /
The reaction can be performed under reduced pressure or increased pressure of cm 2 . Since the target compound (I) produced by the above reaction is precipitated in the reaction solution, it can be easily isolated by filtration or the like and, if necessary, can be purified by recrystallization or the like.
【００１１】[0011]
【実施例】以下、本発明を実施例により更に詳細に説明
するが、本発明は、その要旨を越えない限り実施例によ
り限定されるものではない。EXAMPLES The present invention will be described in more detail with reference to examples below, but the present invention is not limited to the examples as long as the gist thereof is not exceeded.
【００１２】実施例１ トルエン１９１ｍｌに３−シアノ−６−ブロモピリジン
３４．５ｇ（０．１８９モル）を仕込み、９０℃まで昇
温した。次に、４７％臭化水素酸水溶液７６．５ｍｌを
１時間で滴下し還流下２時間反応させたところ白色の結
晶が析出した。この結晶を精製のため濾過し、ジメチル
ホルムアミド１００ｍｌに溶解させた後４００ｍｌの水
に放出した。析出した結晶を濾過し乾燥することにより
６−ブロモニコチン酸２０．２ｇ（純度９８％、収率５
２％）を得た。Example 1 To 191 ml of toluene was charged 34.5 g (0.189 mol) of 3-cyano-6-bromopyridine, and the temperature was raised to 90 ° C. Next, 76.5 ml of 47% hydrobromic acid aqueous solution was added dropwise over 1 hour, and the mixture was reacted under reflux for 2 hours, whereupon white crystals were precipitated. The crystals were filtered for purification, dissolved in 100 ml of dimethylformamide and then released in 400 ml of water. The precipitated crystals were filtered and dried to give 6-bromonicotinic acid (20.2 g, purity 98%, yield 5).
2%).
【００１３】実施例２ ４７％臭化水素酸水溶液の代りに４０％硫酸で実施例１
と同様に反応を行ったところ、６−ブロモニコチン酸１
７．５ｇ（純度９８％、収率４５％）を得た。Example 2 Example 1 was replaced with 40% sulfuric acid instead of 47% hydrobromic acid aqueous solution.
When the reaction was performed in the same manner as in 6-bromonicotinic acid 1
7.5 g (purity 98%, yield 45%) was obtained.
【００１４】比較例１ ４７％臭化水素酸７６．５ｍｌに３−シアノ−６−ブロ
モピリジン３４．５ｇ（０．１８９モル）を仕込み７５
℃で１時間反応した。反応液を液体クロマトグラフィー
で分析したところ、３−シアノ−６−ブロモピリジンの
転化率８１％、６−ブロモニコチン酸は収率で５％であ
った。Comparative Example 1 34.5 g (0.189 mol) of 3-cyano-6-bromopyridine was charged in 76.5 ml of 47% hydrobromic acid.
The reaction was carried out at ℃ for 1 hour. When the reaction liquid was analyzed by liquid chromatography, the conversion of 3-cyano-6-bromopyridine was 81%, and the yield of 6-bromonicotinic acid was 5%.
【００１５】[0015]
【発明の効果】本発明によれば、医薬・農薬等の原体、
中間体として有用な６−ブロモニコチン酸を工業的に有
利な方法で製造することができる。EFFECTS OF THE INVENTION According to the present invention, a drug substance, an agricultural chemical, etc.
6-Bromonicotinic acid, which is useful as an intermediate, can be produced by an industrially advantageous method.
Claims (3)
モニコチン酸を製造するに際し、下記一般式（II）で表
わされる３−シアノ−６−ブロモピリジンを酸水溶液及
び非水溶性有機溶媒からなる二相系混合物中で加水分解
することを特徴とする６−ブロモニコチン酸の製造方
法。 【化１】 【化２】 1. When producing 6-bromonicotinic acid represented by the following general formula (I), 3-cyano-6-bromopyridine represented by the following general formula (II) is added to an aqueous acid solution and a water-insoluble organic solvent. A method for producing 6-bromonicotinic acid, which comprises hydrolyzing in a two-phase mixture comprising Embedded image Embedded image
記載の６−ブロモニコチン酸の製造方法。2. The method for producing 6-bromonicotinic acid according to claim 1, wherein hydrobromic acid is used as the acid.
１に記載の６−ブロモニコチン酸の製造方法。3. The method for producing 6-bromonicotinic acid according to claim 1, wherein toluene is used as the organic solvent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33678895A JPH09176122A (en) | 1995-12-25 | 1995-12-25 | Production of 6-bromonicotinic acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP33678895A JPH09176122A (en) | 1995-12-25 | 1995-12-25 | Production of 6-bromonicotinic acid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09176122A true JPH09176122A (en) | 1997-07-08 |
Family
ID=18302700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP33678895A Pending JPH09176122A (en) | 1995-12-25 | 1995-12-25 | Production of 6-bromonicotinic acid |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH09176122A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319401A (en) * | 2013-05-22 | 2013-09-25 | 中牧实业股份有限公司 | Technology for preparing 2-chromium picolinate through one-step method |
-
1995
- 1995-12-25 JP JP33678895A patent/JPH09176122A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103319401A (en) * | 2013-05-22 | 2013-09-25 | 中牧实业股份有限公司 | Technology for preparing 2-chromium picolinate through one-step method |
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