JP4708548B2 - Method for removing basic impurities of 6-chloronicotine derivative - Google Patents
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Description
【０００１】
【発明の属する技術分野】
本発明は、殺虫剤として有用な化合物である６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液から、簡便かつ確実に塩基性不純物を除去する方法に関する。
【０００２】
【従来の技術】
一般式（１）
【０００３】
【化２】
（式中、Ｘはシアノ基又はニトロ基を表し、ＺはＣＨ又はＮを表し、Ｒ1は、水素原子又は置換基を有してもよいＣ１〜Ｃ６アルキル基を表し、Ｒ2は、置換基を有してもよいＣ１〜Ｃ６アルキル基又は置換基を有してもよい窒素原子を表す。また、Ｒ1とＲ2は結合して環を形成してもよい。）で表わされる化合物（以下、「６−クロロニコチン誘導体」という）は、殺虫性組成物の殺虫活性成分又はその製造中間体として有用である。
【０００５】
かかる化合物の製造プロセスにおいては、通常、得られる反応生成物中に不純物が含まれている。そのため、再結晶や水洗等の精製操作を行っている（特開平５−１７８８３４号公報等参照）。
【０００６】
しかしながら、６−クロロニコチン誘導体と溶解性が近似する不純物が含まれる場合等には、再結晶や水洗等の精製を行っても満足できる程度に該不純物を除去できない場合があった。上述したように、６−クロロニコチン誘導体は殺虫活性成分又はその製造中間体であり、このものが最終製品である場合はもとより、製造中間体である場合においても、次の製造工程の反応収率を高め、最終製品の精製をより容易にするために高純度化が必要とされている。
【０００７】
【発明が解決しようとする課題】
本発明は、かかる実情に鑑みてなされたものであり、６−クロロニコチン誘導体の製造時に含まれる塩基性不純物を、簡便かつ確実に除去する方法を提供することを目的とする。
【０００８】
【課題を解決するための手段】
本発明者らは、６−クロロニコチン誘導体を製造する際の反応生成物中に含まれる不純物を詳細に調べた。その結果、得られた目的物（６−クロロニコチン誘導体）を再結晶し、水洗することによっても十分に除去できない不純物は、ある種の塩基性不純物であることを見出した。そして、得られた６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液に、酸を加えて攪拌し、ろ過することにより、きわめて簡便、かつ確実に塩基性不純物をろ液へ除去できることを見出し、本発明を完成するに至った。
【０００９】
すなわち、本発明は、一般式（１）
【００１０】
【化３】
（式中、Ｘはシアノ基又はニトロ基を表し、ＺはＣＨ又はＮを表し、Ｒ1は、水素原子又は置換基を有してもよいＣ１〜Ｃ６アルキル基を表し、Ｒ2は、置換基を有してもよいＣ１〜Ｃ６アルキル基又は置換基を有してもよい窒素原子を表す。また、Ｒ1とＲ2は結合して環を形成してもよい。）で表される化合物及び不純物を含む溶液又は懸濁液に、酸を添加することを特徴とする塩基性不純物の除去方法を提供する。
【００１２】
本発明においては、前記酸として希硝酸を添加するのが好ましく、また、前記酸を１５〜４５℃で添加するのが好ましい。
また本発明は、前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液の溶媒は、水及びアルコールの混合溶媒であるのが好ましく、前記一般式（１）で表される６−クロロニコチン誘導体を製造した反応液又は反応後処理液であるのがより好ましい。
【００１３】
さらに本発明においては、前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液に、所定量の希硝酸を１５〜４５℃で添加する工程と、得られた前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液を０〜３０℃に冷却する工程と、得られた前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液をろ過することにより、塩基性不純物をろ液中に除去する工程を有するのがより好ましい。
【００１４】
本発明によれば、前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液から、塩基性不純物を簡便かつ確実に除去することができる。また、酸として希硝酸を用いる場合には、製造工程で一般的に使用されるステンレス等の金属材料からなる反応設備を腐食させることがない。
【００１５】
【発明の実施の形態】
本発明は、一般式（１）
【００１６】
【化４】
で表される化合物及びその塩基性不純物を含む溶液又は懸濁液に酸を添加することを特徴とする塩基性不純物の除去方法である。
前記一般式（１）中、Ｘはシアノ基又はニトロ基を表し、ＺはＣＨ又はＮを表す。
Ｒ1は、水素原子又は置換基を有してもよいＣ１〜Ｃ６アルキル基を表す。前記置換基を有してもよいＣ１〜Ｃ６アルキル基のＣ１〜Ｃ６アルキル基の具体例としては、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、ｔ−ブチル基、ｎ−ペンチル基、イソペンチル基、ｎ−ヘキシル基、イソヘキシル基等が挙げられる。
【００１８】
Ｃ１〜Ｃ６アルキル基の置換基としては、メチル基、エチル基、プロピル基等のＣ１〜Ｃ６アルキル基；メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｔ−ブトキシ基等のＣ１〜Ｃ６アルコキシ基；フッ素、塩素等のハロゲン原子；メチルチオ基、エチルチオ基、ｎ−プロピルチオ基、イソプロピルチオ基、ｎ−ブチルチオ基、ｔ−ブチルチオ基等のＣ１〜Ｃ６アルキルチオ基；メチルアミノ基、エチルアミノ基等のＣ１〜Ｃ６アルキルアミノ基；ジメチルアミノ基、ジエチルアミノ基等のジＣ１〜Ｃ６アルキルアミノ基；等が挙げられる。
【００１９】
Ｒ2は、置換基を有してもよいＣ１〜Ｃ６アルキル基又は置換基を有してもよい窒素原子を表す。前記置換基を有してもよいＣ１〜Ｃ６アルキル基のＣ１〜Ｃ６アルキル基の具体例としては、メチル基、エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチル基、ｓｅｃ−ブチル基、ｔ−ブチル基、ｎ−ペンチル基、イソペンチル基、ｎ−ヘキシル基、イソヘキシル基等が挙げられる。
【００２０】
また、Ｃ１〜Ｃ６アルキル基の置換基としては、メチル基、エチル基、プロピル基等のＣ１〜Ｃ６アルキル基；メトキシ基、エトキシ基、ｎ−プロポキシ基、イソプロポキシ基、ｎ−ブトキシ基、ｔ−ブトキシ基等のＣ１〜Ｃ６アルコキシ基；フッ素、塩素等のハロゲン原子；メチルチオ基、エチルチオ基、ｎ−プロピルチオ基、イソプロピルチオ基、ｎ−ブチルチオ基、ｔ−ブチルチオ基等のＣ１〜Ｃ６アルキルチオ基；メチルアミノ基、エチルアミノ基等のＣ１〜Ｃ６アルキルアミノ基；ジメチルアミノ基、ジエチルアミノ基等のジＣ１〜Ｃ６アルキルアミノ基；等が挙げられる。
【００２１】
置換基を有してもよい窒素原子としては、例えば、アミノ基；Ｎ−メチルアミノ基、Ｎ−エチルアミノ基、Ｎ−ｎ−プロピルアミノ基、Ｎ−イソプロピルアミノ基等のＣ１〜Ｃ６アルキルアミノ基；Ｎ，Ｎ−ジメチルアミノ基、Ｎ，Ｎ−ジエチルアミノ基、Ｎ−エチル−Ｎ−メチルアミノ基等のジＣ１〜Ｃ６アルキルアミノ基；Ｎ−メトキシアミノ基、Ｎ−エトキシアミノ基等のＣ１〜Ｃ６アルコキシアミノ基；Ｎ，Ｎ−ジメトキシアミノ基、Ｎ，Ｎ−ジエトキシアミノ基、Ｎ−エトキシ−Ｎ−メトキシアミノ基等のジＣ１〜Ｃ６アルコキシアミノ基；Ｎ−メチル−Ｎ−メトキシアミノ基、Ｎ−メトキシ−Ｎ−エチルアミノ基、Ｎ−エチル−Ｎ−メトキシアミノ基、Ｎ−エチル−Ｎ−エトキシアミノ基等のＮ−Ｃ１〜Ｃ６アルコキシ−Ｎ−Ｃ１〜Ｃ６アルキルアミノ基；等が挙げられる。
【００２２】
また、Ｒ1とＲ2は、一緒になって結合して、５〜８員の複素環を形成してもよい。かかる複素環の具体例としては、ピロリジン環、ピロール環、イミダゾリジン環、イミダゾール環、ヘキサヒドロピリミジン環、テトラヒドロピリミジン環、ピリミジン環、ピペリジン環、ピリジン環等が挙げられる。
前記一般式（１）で表される６−クロロニコチン誘導体の具体例としては、次のものが挙げられる。
【００２３】
【化５】
（式中、ｒはＣ１〜Ｃ６アルキル基等を表す。）
６−クロロニコチン誘導体及び塩基性不純物を含有する溶液又は懸濁液の溶媒には特に制限はない。例えば、水；メタノール、エタノール、プロパノール、イソプロパノール、ブタノール等のアルコール類；ジエチルエーテル、テトラヒドロフラン（ＴＨＦ）、１，２−ジメトキシエタン、１，４−ジオキサン等のエーテル類；アセトン、メチルエチルケトン、メチルイソブチルケトン、シクロヘキサノン等のケトン類；Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセタミド、ヘキサメチルリン酸トリアミド等のアミド類；ベンゼン、トルエン、キシレン、エチルベンゼン等の芳香族系炭化水素類；ジクロロメタン、クロロホルム、四塩化炭素等のハロゲン炭化水素類；ジメチルスルホキシド、アセトニトリル等を用いることができる。これらは単独で、あるいは二種以上の混合溶液して使用することができる。
【００２５】
これらの中でも、６−クロロニコチン誘導体及び塩基性不純物の溶解性の観点から、水−メタノール、水−エタノール、水−ｎ−プロパノール、水−イソプロパノール等の水と低級アルコールとの混合溶媒が好ましい。また、該６−クロロニコチン誘導体及び塩基性不純物を含有する溶液又は懸濁液が、６−クロロニコチン誘導体を製造した反応液又は反応後処理液である場合には、溶媒を交換することなく、そのまま本発明の不純物除去工程に供することができるので特に好ましい。
【００２６】
６−クロロニコチン誘導体混合液中の不純物としては、さまざまなものが考えられるが、例えば、出発原料である６−クロロ−３−ピリジルメチルクロリドや６−クロロ−３−ピリジルメチルアミン由来の塩基性不純物及び該塩基性不純物由来の副生成物等が挙げられる。
【００２７】
塩基性不純物を除去するのに用いられる酸としては、硝酸、塩酸、硫酸等の無機酸が挙げられる。６−クロロニコチン誘導体を工業的スケールで製造する場合は、一般的に、ＳＵＳ（ステンレス鋼）等の金属材料からなる反応設備で行われるため、かかる金属材料が腐食されない程度に希釈したもの使用するのが好ましい。添加する酸の濃度は、通常、０．０１〜１６ｍｏｌ／リットル、好ましくは０．１〜８ｍｏｌ／リットルである。また酸の添加量は、不純物を除去できる量であれば十分であるが、６−クロロニコチン誘導体１当量に対して、通常、０．０１〜０．５当量、好ましくは０．０５〜０．２０当量の範囲である。これらの中でも、濃度０．１ｍｏｌ／リットル〜６ｍｏｌ／リットルの希硝酸は、ＳＵＳ等の金属材料からなる反応設備をほとんど腐食しないことから、特に好ましく用いることができる。
【００２８】
酸を添加する温度は特に制限はないが、通常０〜１００℃、好ましくは１５〜４５℃の範囲である。この温度範囲で酸を滴下する場合には、酸による分解等の副反応を抑制でき、反応設備を腐食することが少なく、かつ効率よく不純物を除去することができる。
【００２９】
６−クロロニコチン誘導体及び塩基性不純物を含有する溶液又は懸濁液から、不純物を除去するには、例えば次のようにして行うことができる。まず、（１）６−クロロニコチン誘導体及び塩基性不純物を含有する溶液又は懸濁液に、所定温度下で所定量の酸を加えて十分に攪拌する。次に、（２）得られた混合物を所定温度まで冷却する。このとき、必要に応じて難溶性溶媒を添加することもできる。（３）次いで、混合物から６−クロロニコチン誘導体の結晶をろ取すると同時に、不純物をろ液へ除去することができる。
【００３０】
６−クロロニコチン誘導体及び塩基性不純物を含有する溶液又は懸濁液が、６−クロロニコチン誘導体を製造した反応液又は反応後処理液である場合には、（１）反応液又は反応後処理液を６０℃〜９０℃に加熱し、好ましくは、６−クロロニコチン誘導体を溶解させたのち、（２）該反応液又は反応後処理液を４０℃〜８０℃に冷却（又は放冷）することにより、目的物の結晶を析出させ（晶析）、さらに、（３）１５〜４５℃で酸を添加したのち、５〜２５℃に冷却し、析出した目的物結晶をろ取することにより、不純物のみをろ液へ除去することができる。
【００３１】
ろ取した６−クロロニコチン誘導体の結晶は、乾燥してそのまま使用することもできるが、さらに水洗を行うのが、酸及び微量の不純物を完全に除去することができるため好ましい。
【００３２】
【実施例】
次に、実施例により本発明を更に詳細に説明するが、本発明は下記実施例に限定されることなく、本発明の主旨を逸脱しない範囲で、一般式（１）で表される化合物及び塩基性不純物の種類、溶媒の種類、用いる酸の種類、酸の濃度などを自由に変更することができる。なお、以下の反応は、すべてＳＵＳ（ステンレス鋼）製の反応容器で行った。
【００３３】
（実施例１）
Ｎ−シアノ−Ｎ’−（６−クロロ−３−ピリジルメチル）アセトアミジンの製造（その１）
【００３４】
【化６】
水２３０ｍｌに純度９７．５％の６−クロロ−３−ピリジルメチルアミン５８．５ｇ（０．４ｍｏｌ）を加え、攪拌下に２５℃に保持しなら、純度９７％のメチル−Ｎ−シアノアセトイミデート４１．４６ｇ（０．４１２ｍｏｌ）を４５分かけて滴下し、滴下終了後、同温度で３０分さらに撹拌した。得られた反応混合物のスラリーにメタノール８１ｍｌを加えて８０℃に加熱し、析出している結晶を溶解させた後、反応液を３５℃まで徐々に冷却した。結晶が析出して、反応液は再びスラリーとなった。次いで、全容を１５℃まで冷却し、２ｍｏｌ／リットルの塩酸２００ｍｌを撹拌しながら滴下した。さらに３０分間撹拌した後、析出した結晶をろ取し、水洗、乾燥して、目的とするＮ−シアノ−Ｎ’−（６−クロロ−３−ピリジルメチル）アセトアミジン７８．８ｇを得た。高速液体クロマトグラフィーにて分析した結果、このものの純度は９９．８％であった。また、この一連の操作を１０回繰り返し行った後、反応容器の腐食等を調べた結果、反応容器の底部に酸による腐食が若干見られた。
【００３６】
（実施例２）
Ｎ−シアノ−Ｎ’−（６−クロロ−３−ピリジルメチル）アセトアミジンの製造（その２）
【００３７】
水２３０ｍｌに純度９７．５％の６−クロロ−３−ピリジルメチルアミン５８．５ｇ（０．４ｍｏｌ）を加え、攪拌下に２５℃に保持しなら、純度９７％のメチル−Ｎ−シアノアセトイミデート４１．４６ｇ（０．４１２ｍｏｌ）を４５分かけて滴下し、滴下終了後、同温度で３０分さらに撹拌した。得られた目的物のスラリーにメタノール８１ｍｌを加えて８０℃に加熱し、析出している結晶を溶解させた後、反応液を３５℃まで徐々に冷却した。結晶が析出して、反応液は再びスラリーとなった。次いで、全容を１５℃に冷却し、２ｍｏｌ／リットルの硝酸２００ｍｌを撹拌しながら滴下した。さらに３０分間撹拌した後、析出した結晶をろ取し、水洗、乾燥して、目的とするＮ−シアノ−Ｎ’−（６−クロロ−３−ピリジルメチル）アセトアミジン７８．７ｇを得た。高速液体クロマトグラフィーにて分析した結果、このものの純度は９９．９％であった。また、この一連の操作を１０回繰り返し行った後、反応容器の腐食等を調べたが、反応容器はまったく腐食されていなかった。
【００３８】
（比較例１）
Ｎ−シアノ−Ｎ’−（６−クロロ−３−ピリジルメチル）アセトアミジンの製造（その３）
水２３０ｍｌに純度９７．５％の６−クロロ−３−ピリジルメチルアミン５８．５ｇ（０．４ｍｏｌ）を加え、冷却攪拌下に２５℃に保持しなら、純度９７％のメチル−Ｎ−シアノアセトイミデート４１．４６ｇ（０．４１２ｍｏｌ）を４５分かけて滴下し、滴下終了後、同温度で３０分さらに撹拌した。反応終了後、得られた目的物のスラリーにメタノール８１ｍｌを加えて８０℃に加熱し、析出結晶を溶解させた後、反応液を１５℃まで徐々に冷却した。結晶が再度析出して、反応液はスラリーとなった。析出した結晶をろ取し、水洗、乾燥して、目的とするＮ−シアノ−Ｎ’−（６−クロロ−３−ピリジルメチル）アセトアミジン７９．１ｇを得た。このものを高速液体クロマトグラフィーにて分析した結果、このものの純度は９４．１％であった。
【００３９】
【発明の効果】
以上説明したように、本発明によれば、殺虫性組成物の殺虫活性成分又はその製造中間体である６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液から、簡便かつ確実に不純物を除去することができる。また、酸として希硝酸を用いる場合には、ＳＵＳ製等の通常の酸により腐食され易い反応設備を腐食することがない。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a method for easily and reliably removing basic impurities from a solution or suspension containing a 6-chloronicotine derivative, which is a compound useful as an insecticide, and basic impurities.
[0002]
[Prior art]
General formula (1)
[0003]
[Chemical 2]
(In the formula, X represents a cyano group or a nitro group, Z represents CH or N, R 1 represents a hydrogen atom or a C1-C6 alkyl group which may have a substituent, and R 2 represents a substituted group. A C1-C6 alkyl group which may have a group or a nitrogen atom which may have a substituent, and R 1 and R 2 may combine to form a ring. (Hereinafter referred to as “6-chloronicotine derivative”) is useful as an insecticidal active ingredient of an insecticidal composition or an intermediate for producing the same.
[0005]
In the production process of such a compound, impurities are usually contained in the obtained reaction product. For this reason, refining operations such as recrystallization and washing are performed (see Japanese Patent Application Laid-Open No. 5-17834).
[0006]
However, when an impurity whose solubility is close to that of the 6-chloronicotine derivative is contained, the impurity may not be removed to a satisfactory degree even if purification such as recrystallization or water washing is performed. As described above, the 6-chloronicotine derivative is an insecticidal active ingredient or a production intermediate thereof. The reaction yield of the next production process is not limited to the case where this product is a final product but also a production intermediate. Higher purity is required in order to increase the quality and make the final product easier to purify.
[0007]
[Problems to be solved by the invention]
This invention is made | formed in view of this situation, and it aims at providing the method of removing the basic impurity contained at the time of manufacture of a 6-chloronicotine derivative simply and reliably.
[0008]
[Means for Solving the Problems]
The present inventors investigated in detail the impurities contained in the reaction product when producing the 6-chloronicotine derivative. As a result, it was found that impurities that cannot be sufficiently removed even by recrystallizing the obtained target product (6-chloronicotine derivative) and washing with water are certain basic impurities. And, by adding an acid to the resulting solution or suspension containing 6-chloronicotine derivative and basic impurities, stirring, and filtering, the basic impurities can be removed extremely easily and reliably into the filtrate. As a result, the present invention has been completed.
[0009]
That is, the present invention relates to the general formula (1)
[0010]
[Chemical 3]
(In the formula, X represents a cyano group or a nitro group, Z represents CH or N, R 1 represents a hydrogen atom or a C1-C6 alkyl group which may have a substituent, and R 2 represents a substituted group. A C1-C6 alkyl group which may have a group or a nitrogen atom which may have a substituent, and R 1 and R 2 may combine to form a ring. Provided is a method for removing basic impurities, which comprises adding an acid to a solution or suspension containing a compound and impurities.
[0012]
In the present invention, it is preferable to add dilute nitric acid as the acid, and it is preferable to add the acid at 15 to 45 ° C.
In the present invention, the solvent of the solution or suspension containing the 6-chloronicotine derivative represented by the general formula (1) and the basic impurity is preferably a mixed solvent of water and alcohol, and the general formula More preferably, it is a reaction solution or a post-reaction treatment solution for producing the 6-chloronicotine derivative represented by (1).
[0013]
Furthermore, in the present invention, a step of adding a predetermined amount of dilute nitric acid at 15 to 45 ° C. to a solution or suspension containing the 6-chloronicotine derivative represented by the general formula (1) and basic impurities; A step of cooling the obtained solution or suspension containing the 6-chloronicotine derivative represented by the general formula (1) and basic impurities to 0 to 30 ° C., and the obtained general formula (1) It is more preferable to have a step of removing the basic impurities in the filtrate by filtering the solution or suspension containing the 6-chloronicotine derivative and the basic impurities.
[0014]
According to the present invention, basic impurities can be easily and reliably removed from a solution or suspension containing a 6-chloronicotine derivative represented by the general formula (1) and basic impurities. Further, when dilute nitric acid is used as the acid, the reaction equipment made of a metal material such as stainless steel generally used in the manufacturing process is not corroded.
[0015]
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a general formula (1)
[0016]
[Formula 4]
A method for removing basic impurities, comprising adding an acid to a solution or suspension containing the compound represented by formula (1) and a basic impurity thereof.
In the general formula (1), X represents a cyano group or a nitro group, and Z represents CH or N.
R 1 represents a hydrogen atom or a C1-C6 alkyl group which may have a substituent. Specific examples of the C1-C6 alkyl group of the C1-C6 alkyl group that may have a substituent include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, Examples include t-butyl group, n-pentyl group, isopentyl group, n-hexyl group, isohexyl group and the like.
[0018]
Examples of the substituent for the C1-C6 alkyl group include a C1-C6 alkyl group such as a methyl group, an ethyl group, and a propyl group; a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, and a t-butoxy group. C1-C6 alkoxy groups such as groups; halogen atoms such as fluorine and chlorine; C1-C6 alkylthio groups such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, and t-butylthio; methyl A C1-C6 alkylamino group such as an amino group or an ethylamino group; a diC1-C6 alkylamino group such as a dimethylamino group or a diethylamino group;
[0019]
R 2 represents a C1-C6 alkyl group which may have a substituent or a nitrogen atom which may have a substituent. Specific examples of the C1-C6 alkyl group of the C1-C6 alkyl group that may have a substituent include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, a sec-butyl group, Examples include t-butyl group, n-pentyl group, isopentyl group, n-hexyl group, isohexyl group and the like.
[0020]
Moreover, as a substituent of a C1-C6 alkyl group, C1-C6 alkyl groups, such as a methyl group, an ethyl group, a propyl group; a methoxy group, an ethoxy group, n-propoxy group, an isopropoxy group, n-butoxy group, t -C1-C6 alkoxy groups such as butoxy group; halogen atoms such as fluorine and chlorine; C1-C6 alkylthio groups such as methylthio group, ethylthio group, n-propylthio group, isopropylthio group, n-butylthio group, t-butylthio group A C1-C6 alkylamino group such as a methylamino group or an ethylamino group; a diC1-C6 alkylamino group such as a dimethylamino group or a diethylamino group;
[0021]
Examples of the nitrogen atom that may have a substituent include an amino group; C1-C6 alkylamino such as N-methylamino group, N-ethylamino group, Nn-propylamino group, and N-isopropylamino group. Groups; di-C1-C6 alkylamino groups such as N, N-dimethylamino group, N, N-diethylamino group, N-ethyl-N-methylamino group; C1 such as N-methoxyamino group and N-ethoxyamino group -C6 alkoxyamino group; di-C1-C6 alkoxyamino group such as N, N-dimethoxyamino group, N, N-diethoxyamino group, N-ethoxy-N-methoxyamino group; N-methyl-N-methoxyamino N-C1-C6 alkoxy-NC such as N-methoxy-N-ethylamino group, N-ethyl-N-methoxyamino group, N-ethyl-N-ethoxyamino group ~C6 alkylamino group; and the like.
[0022]
R 1 and R 2 may be bonded together to form a 5- to 8-membered heterocyclic ring. Specific examples of the heterocyclic ring include pyrrolidine ring, pyrrole ring, imidazolidine ring, imidazole ring, hexahydropyrimidine ring, tetrahydropyrimidine ring, pyrimidine ring, piperidine ring, pyridine ring and the like.
Specific examples of the 6-chloronicotine derivative represented by the general formula (1) include the following.
[0023]
[Chemical formula 5]
(In the formula, r represents a C1-C6 alkyl group or the like.)
There is no restriction | limiting in particular in the solvent of the solution or suspension containing a 6-chloronicotine derivative and a basic impurity. For example, water; alcohols such as methanol, ethanol, propanol, isopropanol, butanol; ethers such as diethyl ether, tetrahydrofuran (THF), 1,2-dimethoxyethane, 1,4-dioxane; acetone, methyl ethyl ketone, methyl isobutyl ketone Ketones such as cyclohexanone; amides such as N, N-dimethylformamide, N, N-dimethylacetamide and hexamethylphosphoric triamide; aromatic hydrocarbons such as benzene, toluene, xylene and ethylbenzene; dichloromethane , Halogen hydrocarbons such as chloroform and carbon tetrachloride; dimethyl sulfoxide, acetonitrile and the like can be used. These can be used alone or as a mixture of two or more.
[0025]
Among these, from the viewpoint of solubility of 6-chloronicotine derivatives and basic impurities, a mixed solvent of water and a lower alcohol such as water-methanol, water-ethanol, water-n-propanol, and water-isopropanol is preferable. Further, when the solution or suspension containing the 6-chloronicotine derivative and the basic impurity is a reaction solution or a post-reaction treatment solution for producing the 6-chloronicotine derivative, without changing the solvent, Since it can use for the impurity removal process of this invention as it is, it is especially preferable.
[0026]
Various impurities are conceivable as the impurities in the 6-chloronicotine derivative mixed solution. For example, basic substances derived from 6-chloro-3-pyridylmethyl chloride or 6-chloro-3-pyridylmethylamine which are starting materials. Examples include impurities and by-products derived from the basic impurities.
[0027]
Examples of the acid used for removing the basic impurities include inorganic acids such as nitric acid, hydrochloric acid, and sulfuric acid. When the 6-chloronicotine derivative is produced on an industrial scale, since it is generally performed in a reaction facility made of a metal material such as SUS (stainless steel), the metal material is diluted to such an extent that it is not corroded. Is preferred. The concentration of the acid to be added is usually 0.01 to 16 mol / liter, preferably 0.1 to 8 mol / liter. The acid may be added in an amount that can remove impurities, but is usually 0.01 to 0.5 equivalents, preferably 0.05 to 0.00 equivalents per equivalent of 6-chloronicotine derivative. The range is 20 equivalents. Among these, dilute nitric acid having a concentration of 0.1 mol / liter to 6 mol / liter can be particularly preferably used because it hardly corrodes reaction equipment made of a metal material such as SUS.
[0028]
The temperature for adding the acid is not particularly limited, but is usually in the range of 0 to 100 ° C, preferably 15 to 45 ° C. When the acid is dropped in this temperature range, side reactions such as decomposition by the acid can be suppressed, the reaction equipment is hardly corroded, and impurities can be efficiently removed.
[0029]
To remove impurities from a solution or suspension containing a 6-chloronicotine derivative and basic impurities, for example, the following can be performed. First, (1) a predetermined amount of acid is added to a solution or suspension containing a 6-chloronicotine derivative and a basic impurity at a predetermined temperature and sufficiently stirred. Next, (2) the obtained mixture is cooled to a predetermined temperature. At this time, a hardly soluble solvent can also be added as needed. (3) Next, the crystals of the 6-chloronicotine derivative are filtered from the mixture, and at the same time, impurities can be removed to the filtrate.
[0030]
When the solution or suspension containing the 6-chloronicotine derivative and the basic impurity is a reaction solution or a post-reaction treatment solution produced from the 6-chloronicotine derivative, (1) a reaction solution or a post-reaction treatment solution Is heated to 60 ° C. to 90 ° C., and preferably the 6-chloronicotine derivative is dissolved, and then (2) the reaction solution or the post-reaction treatment solution is cooled (or allowed to cool) to 40 ° C. to 80 ° C. (3) After adding an acid at 15 to 45 ° C., cooling to 5 to 25 ° C., and collecting the precipitated target crystal by filtration, Only impurities can be removed to the filtrate.
[0031]
The 6-chloronicotine derivative crystals collected by filtration can be dried and used as they are, but it is preferable to perform washing with water since the acid and trace amounts of impurities can be completely removed.
[0032]
【Example】
EXAMPLES Next, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples, and the compound represented by the general formula (1) and the scope of the present invention are within the scope of the present invention. The kind of basic impurities, the kind of solvent, the kind of acid used, the concentration of acid, etc. can be freely changed. The following reactions were all performed in a reaction vessel made of SUS (stainless steel).
[0033]
Example 1
Production of N-cyano-N ′-(6-chloro-3-pyridylmethyl) acetamidine (Part 1)
[0034]
[Chemical 6]
If 58.5 g (0.4 mol) of 97.5% pure 6-chloro-3-pyridylmethylamine is added to 230 ml of water, and kept at 25 ° C. with stirring, then 97% pure methyl-N-cyanoacetimidium is obtained. Date 41.46 g (0.412 mol) was added dropwise over 45 minutes. After completion of the addition, the mixture was further stirred at the same temperature for 30 minutes. After 81 ml of methanol was added to the resulting slurry of the reaction mixture and heated to 80 ° C. to dissolve the precipitated crystals, the reaction solution was gradually cooled to 35 ° C. Crystals precipitated, and the reaction solution became a slurry again. The whole volume was then cooled to 15 ° C., and 200 ml of 2 mol / liter hydrochloric acid was added dropwise with stirring. After further stirring for 30 minutes, the precipitated crystals were collected by filtration, washed with water and dried to obtain 78.8 g of the target N-cyano-N ′-(6-chloro-3-pyridylmethyl) acetamidine. As a result of analysis by high performance liquid chromatography, the purity of this product was 99.8%. Further, after repeating this series of operations 10 times, the corrosion of the reaction vessel was examined, and as a result, some corrosion due to acid was observed at the bottom of the reaction vessel.
[0036]
(Example 2)
Production of N-cyano-N ′-(6-chloro-3-pyridylmethyl) acetamidine (Part 2)
[0037]
If 58.5 g (0.4 mol) of 97.5% pure 6-chloro-3-pyridylmethylamine is added to 230 ml of water, and kept at 25 ° C. with stirring, then 97% pure methyl-N-cyanoacetimidium is obtained. Date 41.46 g (0.412 mol) was added dropwise over 45 minutes. After completion of the addition, the mixture was further stirred at the same temperature for 30 minutes. 81 ml of methanol was added to the resulting slurry of the target product and heated to 80 ° C. to dissolve the precipitated crystals, and then the reaction solution was gradually cooled to 35 ° C. Crystals precipitated, and the reaction solution became a slurry again. Subsequently, the whole volume was cooled to 15 ° C., and 200 ml of 2 mol / liter nitric acid was added dropwise with stirring. After further stirring for 30 minutes, the precipitated crystals were collected by filtration, washed with water, and dried to obtain 78.7 g of the target N-cyano-N ′-(6-chloro-3-pyridylmethyl) acetamidine. As a result of analysis by high performance liquid chromatography, the purity of this product was 99.9%. Further, after repeating this series of operations 10 times, the reaction vessel was examined for corrosion and the like, but the reaction vessel was not corroded at all.
[0038]
(Comparative Example 1)
Production of N-cyano-N ′-(6-chloro-3-pyridylmethyl) acetamidine (Part 3)
If 58.5 g (0.4 mol) of 97.5% pure 6-chloro-3-pyridylmethylamine is added to 230 ml of water and kept at 25 ° C. with cooling and stirring, methyl-N-cyanoacetate having a purity of 97% 41.46 g (0.412 mol) of imidate was added dropwise over 45 minutes, and after completion of the addition, the mixture was further stirred at the same temperature for 30 minutes. After completion of the reaction, 81 ml of methanol was added to the obtained slurry of the target product and heated to 80 ° C. to dissolve the precipitated crystals, and then the reaction solution was gradually cooled to 15 ° C. Crystals precipitated again, and the reaction solution became a slurry. The precipitated crystals were collected by filtration, washed with water, and dried to obtain 79.1 g of the target N-cyano-N ′-(6-chloro-3-pyridylmethyl) acetamidine. As a result of analyzing the product by high performance liquid chromatography, the purity of the product was 94.1%.
[0039]
【The invention's effect】
As described above, according to the present invention, impurities can be easily and reliably obtained from a solution or suspension containing a 6-chloronicotine derivative that is an insecticidal active ingredient of an insecticidal composition or a production intermediate thereof and a basic impurity. Can be removed. In addition, when dilute nitric acid is used as the acid, the reaction equipment that is easily corroded by a normal acid such as SUS is not corroded.
Claims (4)
で表される６−クロロニコチン誘導体及び塩基性不純物を含む、水及びアルコールの混合溶媒溶液又は水及びアルコールの混合溶媒の懸濁液に、６−クロロニコチン誘導体１当量に対して、０．０１〜０．５当量の酸を１５〜４５℃で添加し、攪拌する工程と、
得られた混合物をろ過することにより、塩基性不純物をろ液中に除去する工程と
を有する６−クロロニコチン誘導体の塩基性不純物除去方法。General formula (1)
The water-alcohol mixed solvent solution or the water-alcohol mixed solvent suspension containing the 6-chloronicotine derivative represented by formula (1) and basic impurities is 0.01 to 1 equivalent of the 6-chloronicotine derivative. Adding ~ 0.5 equivalent of acid at 15-45 ° C and stirring;
A method for removing basic impurities of a 6-chloronicotine derivative , comprising: removing the basic impurities in the filtrate by filtering the obtained mixture .
得られた前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液を０〜３０℃に冷却する工程と、
得られた前記一般式（１）で表される６−クロロニコチン誘導体及び塩基性不純物を含む溶液又は懸濁液をろ過することにより、塩基性不純物をろ液中に除去する工程とを有する
請求項１〜３のいずれかに記載の６−クロロニコチン誘導体の塩基性不純物除去方法。In a mixed solvent solution of water and alcohol or a mixed solvent suspension of water and alcohol containing the 6-chloronicotine derivative represented by the general formula (1) and basic impurities , the concentration is 0 at 15 to 45 ° C. Adding 0.01 to 0.5 equivalent of 1 mol / liter to 6 mol / liter of dilute nitric acid to 1 equivalent of 6-chloronicotine derivative and stirring ;
Cooling the obtained solution or suspension containing the 6-chloronicotine derivative represented by the general formula (1) and basic impurities to 0 to 30 ° C .;
A step of removing the basic impurities in the filtrate by filtering the obtained solution or suspension containing the 6-chloronicotine derivative represented by the general formula (1) and the basic impurities. Item 4. A method for removing a basic impurity of a 6-chloronicotine derivative according to any one of Items 1 to 3 .
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61195164A (en) * | 1985-02-22 | 1986-08-29 | インペリアル・ケミカル・インダストリーズ・ピーエルシー | Chromogenic pyrazine compound and manufacture |
| JPH05178834A (en) * | 1991-12-26 | 1993-07-20 | Nippon Soda Co Ltd | Production of n-cyanoacetamidine derivative |
| JPH05310713A (en) * | 1992-05-13 | 1993-11-22 | Asahi Denka Kogyo Kk | Treatment of benzotriazole compound |
| JPH08506567A (en) * | 1992-11-12 | 1996-07-16 | ビーエーエスエフ アクチェンゲゼルシャフト | Herbicidal sulfonylureas, their manufacture and their use |
-
2000
- 2000-11-06 JP JP2000337076A patent/JP4708548B2/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61195164A (en) * | 1985-02-22 | 1986-08-29 | インペリアル・ケミカル・インダストリーズ・ピーエルシー | Chromogenic pyrazine compound and manufacture |
| JPH05178834A (en) * | 1991-12-26 | 1993-07-20 | Nippon Soda Co Ltd | Production of n-cyanoacetamidine derivative |
| JPH05310713A (en) * | 1992-05-13 | 1993-11-22 | Asahi Denka Kogyo Kk | Treatment of benzotriazole compound |
| JPH08506567A (en) * | 1992-11-12 | 1996-07-16 | ビーエーエスエフ アクチェンゲゼルシャフト | Herbicidal sulfonylureas, their manufacture and their use |
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| JP2002145862A (en) | 2002-05-22 |
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