JP3720637B2 - New nitroisourea derivatives - Google Patents
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- JP3720637B2 JP3720637B2 JP19686999A JP19686999A JP3720637B2 JP 3720637 B2 JP3720637 B2 JP 3720637B2 JP 19686999 A JP19686999 A JP 19686999A JP 19686999 A JP19686999 A JP 19686999A JP 3720637 B2 JP3720637 B2 JP 3720637B2
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Description
【０００１】
【発明の属する技術分野】
本発明は新規なニトロイソウレア誘導体とその製造方法および該ニトロイソウレア誘導体を用いた殺虫活性を有するニトログアニジン誘導体の製造方法に関するものである。
【０００２】
【従来の技術】
殺虫活性を有するニトログアニジン誘導体およびその製造方法は、特開平２−２８８８６０、特開平３−１５７３０８、特開平７−１７９４４８等に開示されている。しかしながら、例えば特開平７−１７９４４８等に代表されるように、その製造方法はイソチオウレア誘導体とアミン類の交換反応が多く、そのため悪臭を有するメルカプタン類が副生成物として脱離するという欠点があった。
これに代わる方法として、特開平１０−１２０６６６には、式（Ａ）（化８）で表されるイソウレア化合物またはその塩をアミン類またはその塩とを反応させて、式（Ｂ）（化９）で表される殺虫活性を有するグアニジン誘導体の製造方法が開示されている。
【０００３】
【化８】
【０００４】
【化９】
【０００５】
しかしながら本方法によれば、殺虫活性を有する式（Ｂ）で表されるグアジニン誘導体を製造するために、高価な式（Ａ）で表されるイソウレア化合物を中間体として使用しなければならないことの不都合があった。
【０００６】
【発明が解決しようとする課題】
本発明の目的は、上記従来技術の欠点を克服した、殺虫活性を有するグアジニン誘導体の製造のための中間体として重要な新規のニトロイソウレア誘導体を提供することにある。すなわち、本発明の課題は、安価で、殺虫活性を有する種々のグアジニン誘導体の製造のための中間体として有用な新規なニトロイソウレア誘導体を提供すること、しかもその製造工程において悪臭を有するメルカプタン類を副生しない製造方法、および該ニトロイソウレア誘導体を用いた殺虫活性を有するニトログアニジン誘導体の製造方法を提供することにある。
【０００７】
【課題を解決するための手段】
本発明者らは、上記課題を解決すべく鋭意検討した結果、殺虫活性を有するニトログアニジン誘導体を製造する際の重要中間体として、特開平１０−１２０６６６号公報に記載されている式（Ａ）で表されるイソウレア化合物とは異なるニトロイソウレア誘導体を見出し、該ニトロイソウレア誘導体を用いることにより、容易に種々の殺虫活性を有するニトログアニジン誘導体を製造できることを見出し、本発明を完成させた。
【０００８】
すなわち本発明１つは、式（１）（化１０）
【化１０】
【０００９】
また、本発明の１つは、式（２）（化１１）
【化１１】
で表されるニトロイソウレア類と、式（３）（化１２）
【００１０】
【化１２】
【００１１】
さらにまた本発明の１つは、前記式（１）で表されるニトロイソウレア誘導体と式（４）（化１３）
【化１３】
【００１２】
【化１４】
【００１３】
【発明の実施の形態】
以下に本発明を詳細に説明する。
本発明において、Ｒ1、Ｒ2、Ｒ3、Ｒ4、Ｒ5、Ｒ6の炭素数１〜４のアルキル基としてはメチル基、エチル基、プロピル基、ｉ−プロピル基、ブチル基、ｉ−ブチル基、ｔ−ブチル基等を例示することができる。また、Ｑの少なくとも窒素原子、酸素原子、硫黄原子を１つ含む、ハロゲン原子で置換されていてもよい５員または６員の複素環基としては、ピリジル基、ピリダジル基、ピリミジル基、ピラゾリル基、イミダゾリル基、フラニル基、テトラヒドロフラニル基、イソオキサゾリル基、オキサゾリル基、チエニル基、テトラヒドロチエニル基、チアゾリル基、イソチアゾリル基等を例示することができる。
本発明において、Ｒ1とＲ2は各々独立して炭素数１〜４のアルキル基であることが好ましく、Ｒ3は水素原子が好ましく、Ｒ4、Ｒ5とＲ6は、水素原子が好ましい。この中で、殺虫活性が優れている点で、Ｑは２−クロロ−５−チアゾリル基、２−クロロ−５−ピリジニル基、３−テトラヒドロフラニル基であることが好ましい。
【００１４】
式（１）で表される本発明の化合物は新規化合物であり、これらは反応式（１）（化１５）に記載の方法により製造することができる。
【００１５】
【化１５】
【００１６】
反応式（１）において、式（２）で表される化合物と式（３）で表される公知のアミン類またはその塩を、溶媒中、ｐＨを７．０から９．０に、好ましくはｐＨを７．０から８．０に調整して反応させることにより式（１）で表されるニトロイソウレア誘導体を製造することができる。ｐＨが７．０より低いと反応が殆ど進行せず、ｐＨが９．０を越えると目的物が得られない。
【００１７】
式（３）で表されるアミン類と塩を形成する酸類としては、塩酸、硫酸、リン酸等の鉱酸類、メタンスルホン酸、ｐ−トルエンスルホン酸等のスルホン酸類、酢酸、プロピオン酸等のカルボン酸類等を挙げることができる。
【００１８】
反応式（１）で表される反応に用いられる溶媒としては、水、メタノール、エタノール等のアルコール類、ジメチルホルムアミド（ＤＭＦ）、ジメチルスルホキシド（ＤＭＳＯ）、１，３−ジメチル−２−イミダゾリジノン（ＤＭＩ）等の非プロトン性極性溶媒、テトラヒドロフラン（ＴＨＦ）、ジオキサン等のエーテル類、アセトニトリル、プロピオニトリル等のニトリル類、アセトン等のケトン類等を挙げることができる。
【００１９】
反応式（１）で表される反応におけるｐＨの調整には、塩酸、硫酸、リン酸等の鉱酸類に代表される酸類と、水酸化ナトリウム、水酸化カリウム等の水酸化アルカリ金属類に代表される塩基類の組み合わせや、また、ホウ酸ナトリウム−塩酸等の一般緩衝液やトリス−塩酸緩衝液やトリエタノールアミン−塩酸緩衝液等の特殊緩衝液に代表される緩衝液を用いることができる。
式（３）で表されるアミン類およびその塩の使用する量は、式（２）で表される化合物に対して１〜２当量が好ましく、より好ましくは１〜１．１当量である。
【００２０】
反応式（１）において、式（２）で表される化合物は公知化合物であり、例えば、Ｒｅｃｌ．Ｔｒａｖ．Ｃｈｉｍ．Ｐａｙｓ−Ｂａｓ，１９６２年，８１巻，６９頁に記載されているように１−メチルイソウレア硫酸塩のニトロ化により製造することができる。
【００２１】
上記反応の反応温度および反応時間は広範囲に変化させることができる。一般的には、反応温度は−２０〜２００℃が好ましく、より好ましくは０〜１００℃、反応時間は０．０１〜５０時間が好ましく、より好ましくは０．１〜１５時間である。
式（１）で表されるニトロイソウレア誘導体は、Ｒ3が水素原子の場合、下式（化１６）に示すように、その互変異性体が任意の割合で存在し得る。この異性体ならびにその混合物も本発明に包含される。
【００２２】
【化１６】
このようにして製造された式（１）で表されるニトロイソウレア誘導体から、下記反応式（２）（化１７）により、式（５）で表される殺虫活性を有するニトログアニジン誘導体を製造することができる。
【００２４】
【化１７】
【００２５】
反応式（２）において、式（１）で表されるニトロイソウレア誘導体を式（４）で表されるアミン類またはその塩と溶媒中、塩基の非存在下または存在下に反応させることにより、式（５）で表される殺虫活性を有するニトログアニジン誘導体を製造することができる。
【００２６】
反応式（２）で表される反応に用いられる塩基としては、水酸化ナトリウム、水酸化カリウム等のアルカリ金属の水酸化物類、水酸化マグネシウム、水酸化カルシウム等のアルカリ土類金属の水酸化物類、水素化ナトリウム、水素化カリウム等のアルカリ金属の水素化物類、ナトリウムメトキシド、ナトリウムエトキシド等のアルカリ金属のアルコラート類、酸化ナトリウム等のアルカリ金属酸化物類、炭酸カリウム、炭酸ナトリウム等のアルカリ金属の炭酸塩類、リン酸三カリウム、リン酸三ナトリウム、リン酸一水素二カリウム、リン酸一水素二ナトリウム等のアルカリ金属のリン酸塩類、酢酸ナトリウム、酢酸カリウム等のアルカリ金属の酢酸塩類、ピリジン、４−（ジメチルアミノ）ピリジン、トリエチルアミン、ジアザビシクロウンデセン（ＤＢＵ）等の有機塩基類を挙げることができる。
【００２７】
反応式（２）で表される反応に用いられる溶媒としては、水、メタノール、エタノール、プロパノール、ブタノール等のアルコール類、ジクロロメタン、クロロホルム等のハロゲン化炭化水素類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、ジメチルホルムアミド（ＤＭＦ）、ジメチルアセトアミド（ＤＭＡ）、ジメチルスルホキシド（ＤＭＳＯ）、１，３−ジメチル−２−イミダゾリジノン（ＤＭＩ）、１−メチル−２−ピロリドン（ＮＭＰ）等の非プロトン性極性溶媒、エチルエーテル、イソプロピルエーテル、１，２−ジメトキシエタン（ＤＭＥ）、テトラヒドロフラン（ＴＨＦ）、ジオキサン等のエーテル類、アセトニトリル、プロピオニトリル等のニトリル類、アセトン、イソプロピルケトン等のケトン類等を挙げることができる。これらの中で、特に、水、アルコール類が好ましい。
【００２８】
式（４）で表されるアミン類の使用する量は、式（１）で表されるニトロイソウレア誘導体に対し、１〜２当量が好ましく、より好ましくは１〜１．２当量である。
反応式（２）で表される反応の反応温度および反応時間は広範囲に変化させることができる。一般的には、反応温度は−２０℃〜２００℃が好ましく、より好ましくは０〜１００℃、反応時間は０．０１〜５０時間が好ましく、より好ましくは０．１〜１５時間である。
【００２９】
反応式（２）において、式（４）で表されるアミン類は公知化合物であり、例えばＤＥ３７２７１２６Ａ、特開平５−２８６９３６、特開平７−１７９４４８、ＥＰ４４６９１３Ａ、特開平４−２１６７４等に記載の方法により製造できる。
反応式（２）において、式（４）で表されるアミン類と塩を形成する酸類としては、塩酸、硫酸、リン酸等の鉱酸類、メタンスルホン酸、ｐ−トルエンスルホン酸等のスルホン酸類、酢酸、プロピオン酸等のカルボン酸類等を挙げることができる。
このようにして得られた式（５）で表されるニトログアジニン誘導体は、優れた殺虫活性を示す。
【００３０】
【実施例】
次に、実施例および参考例により本発明の内容を具体的に説明するが、本発明はこれに限定されるものではない。
実施例１ １，３−ジメチル−２−ニトロイソウレアの製造（化合物１−１）
１−メチル−２−ニトロイソウレア１．５ｇに水１５ｍｌを加えて懸濁させ、これにメチルアミンの塩酸塩０．９ｇを加えた（ｐＨ＝３．３）。懸濁水溶液にｐＨを８に保つように１％水酸化ナトリウム水溶液を室温にてゆっくりと加えた。懸濁水溶液のｐＨを８に保ちながら室温にて３時間撹拌した後、塩酸水溶液（４Ｍ）を加え、続いて酢酸エチルにて抽出した。有機層を水で洗浄した後、無水硫酸マグネシウムにて乾燥し、減圧濃縮した。得られた油状物をシリカゲルカラムクロマトグラフィー（２：１ヘキサン／酢酸エチル）にて精製した後、再結晶（酢酸エチル−ヘキサン）を行うことにより、標記化合物１．０ｇを無色の結晶として得た。
1H-NMR(CDCl3,ppm):3.02(3H,d,J=4.9Hz),3.97(3H,s),9.10(1H,s)
【００３１】
実施例２ １，３−ジメチル−２−ニトロイソウレアの製造（化合物１−１）
１−メチル−２−ニトロイソウレア１．０ｇをトリス（ヒドロキシメチル）アミノメタン−塩酸緩衝水溶液（トリス−塩酸緩衝溶液、１．０Ｍ、ｐＨ＝７．５）１０ｍｌに懸濁させ、これにメチルアミンの塩酸塩０．６ｇを室温にて加えた。３時間攪拌した後、塩酸水溶液（４Ｍ）を加え、続いて酢酸エチルにて抽出した。有機層を水で洗浄した後、無水硫酸マグネシウムにて乾燥し、減圧濃縮した。得られた油状物をシリカゲルカラムクロマトグラフィー（２：１ヘキサン／酢酸エチル）にて精製した後、再結晶（酢酸エチル−ヘキサン）を行うことにより、標記化合物０．８ｇを無色の結晶として得た。
【００３２】
比較例１
１−メチル−２−ニトロイソウレア１．０ｇを水１０ｍｌに懸濁させ、これにメチルアミンの塩酸塩０．６ｇを加えた（ｐＨ＝３．３）。懸濁水溶液にｐＨを６．５に保つようにゆっくりと１％水酸化ナトリウム水溶液を室温にて加えた。懸濁水溶液のｐＨを６．５に保ちながら室温にて撹拌したが、反応は全く進行しなかった。
【００３３】
比較例２
１−メチル−２−ニトロイソウレア１．０ｇを水１０ｍｌに懸濁させ、これにメチルアミン塩酸塩０．６ｇを加えた（ｐＨ＝３．３）。懸濁水溶液にｐＨを６．９に保つようにゆっくりと１％水酸化ナトリウム水溶液を室温にて加えた。懸濁水溶液のｐＨを６．９に保ちながら室温にて攪拌したが、反応は全く進行せず、標記化合物は得られなかった。
【００３４】
比較例３
１−メチル−２−ニトロイソウレア１．０ｇを水１０ｍｌに懸濁させ、これにメチルアミン塩酸塩０．６ｇを加えた（ｐＨ＝３．３）。懸濁水溶液にｐＨが９．１を保つようにゆっくりと１％水酸化ナトリウム水溶液を室温にて加えた。懸濁水溶液のｐＨを９．１に保ちながら室温にて３時間攪拌した。反応液をジクロロメタンで抽出した後、有機層を無水硫酸マグネシウムにて乾燥した。有機層を減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（２：１ ヘキサン／酢酸エチル）で精製した後、再結晶（酢酸エチル−ヘキサン）を行ったところ、目的化合物は得られず、１−メチル−２−ニトログアニジン０．９ｇが無色の結晶として得られた。
【００３５】
以下に実施例１、２と同様にして製造できる化合物を第１表（表１）に示す。なお、第１表中のMeはメチル基を、Etはエチル基を、n-Prはn-プロピル基を、i-Prはイソプロピル基を、n-Buはn-ブチル基を、Bnはベンジル基を表すものとする。
【００３６】
【表１】
実施例３ １−［（２−クロロ−５−ピリジル）メチル］−３−メチル−２−ニトログアニジン（化合物２−１）の製造
１，３−ジメチル−２−ニトロイソウレア１．０ｇのメタノール１０ｍｌ溶液に［（２−クロロ−５−ピリジル）メチル］アミン１．２８ｇを加え、室温にて５時間撹拌した。反応液を減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（酢酸エチル）にて精製した後に再結晶（メタノール−エーテル）して、標記化合物１．４０ｇを無色の結晶として得た。
実施例４ １−［（２−クロロ−５−チアゾリル）メチル］−３−メチル−２−ニトログアニジン（化合物２−２）の製造
１，３−ジメチル−２−ニトロイソウレア１．０ｇのメタノール１０ｍｌ溶液に［（２−クロロ−５−チアゾリル）メチル］アミン１．３２ｇを加え、室温にて４時間撹拌した。反応液を減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（酢酸エチル）にて精製した後に再結晶（メタノール−エーテル）して、標記化合物１．１１ｇを淡黄色の結晶として得た。
実施例５ １−メチル−２−ニトロ−３−［（３−テトラヒドロフリル）メチル］グアニジンの製造
１，３−ジメチル−２−ニトロイソウレア１．０ｇのメタノール１０ｍｌ溶液に［（３−テトラヒドロフリル）メチル］アミン０．９１ｇを加え、室温にて３時間撹拌した。反応液を減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（酢酸エチル）にて精製した後に再結晶（メタノール−エーテル）して、標記化合物１．４４ｇを無色の結晶として得た。
実施例６ １−［（２−クロロ−５−ピリジル）メチル］−３−メチル−２−ニトログアニジン（化合物２−１）の製造
１，３−ジメチル−２−ニトロイソウレア１．０ｇを水１０ｍｌに懸濁させ、これに［（２−クロロ−５−ピリジル）メチル］アミン１．２８ｇを加え、室温にて３時間攪拌した。反応液を水で希釈した後、ジクロロメタンで抽出した。有機層を無水硫酸マグネシウムにて乾燥後、減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（酢酸エチル）および再結晶（メタノール−エーテル）にて精製することで標記化合物１．２３ｇを無色の結晶として得た。
【００４１】
実施例７ １−［（２−クロロ−５−チアゾリル）メチル］−３−メチル−２−ニトログアニジン（化合物２−２）の製造
１，３−ジメチル−２−ニトロイソウレア１．０ｇを水１０ｍｌに懸濁させ、これに［（２−クロロ−５−チアゾリル）メチル］アミン１．３２ｇを加え、室温にて５時間攪拌した。反応液を水で希釈した後、ジクロロメタンで抽出した。有機層を無水硫酸マグネシウムにて乾燥後、減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（酢酸エチル）および再結晶（メタノール−エーテル）にて精製することで標記化合物０．９５ｇを淡黄色の結晶として得た。
【００４２】
実施例８ １−メチル−２−ニトロ−３−［（３−テトラヒドロフリル）メチル］グアニジン（化合物２−３）の製造
１，３−ジメチル−２−ニトロイソウレア１．０ｇを水１０ｍｌに懸濁させ、［（３−テトラヒドロフリル）メチル］アミン０．９１ｇを加え、室温にて４時間攪拌した。反応液を水で希釈した後、ジクロロメタンで抽出した。有機層を無水硫酸マグネシウムにて乾燥後、減圧濃縮して得られた油状物をシリカゲルカラムクロマトグラフィー（酢酸エチル）および再結晶（メタノール−エーテル）にて精製することで標記化合物１．２４ｇを無色の結晶として得た。
以下に実施例３〜８と同様にして製造できる化合物を第２表（表２、表３、表４）に示す。なお、第２表中のMeはメチル基を、Etはエチル基を、n-Prはn-プロピル基を、i-Prはイソプロピル基を、n-Buはn-ブチル基を表すものとする。
【００４３】
【表２】
【表３】
【表４】
【発明の効果】
式（１）で表される本発明化合物は新規な化合物であり、しかも本化合物と式（４）で表される種々のアミン類との反応により、悪臭を有するメルカプタンを副生せずに、殺虫活性を有する種々のニトログアニジン誘導体を容易に製造できる。従って、式（１）で表される本発明化合物は殺虫活性を有するニトログアニジン誘導体製造の重要中間体として適用することができる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel nitroisourea derivative, a process for producing the same, and a process for producing a nitroguanidine derivative having insecticidal activity using the nitroisourea derivative.
[0002]
[Prior art]
Nitroguanidine derivatives having insecticidal activity and methods for producing the same are disclosed in JP-A-2-288860, JP-A-3-157308, JP-A-7-179448 and the like. However, as represented by, for example, JP-A-7-179448, the production method has many exchange reactions between isothiourea derivatives and amines, and therefore has the disadvantage that mercaptans having a bad odor are eliminated as by-products. It was.
As an alternative method, Japanese Patent Application Laid-Open No. 10-120666 discloses that an isourea compound represented by the formula (A) (Chemical Formula 8) or a salt thereof is reacted with an amine or a salt thereof to give a formula (B) (Chemical Formula 9). A method for producing a guanidine derivative having an insecticidal activity represented by:
[0003]
[Chemical 8]
[0004]
[Chemical 9]
[0005]
However, according to this method, in order to produce a guanidine derivative represented by the formula (B) having insecticidal activity, an expensive isourea compound represented by the formula (A) must be used as an intermediate. There was an inconvenience.
[0006]
[Problems to be solved by the invention]
The object of the present invention is to provide a novel nitroisourea derivative which is important as an intermediate for the production of a guanidine derivative having insecticidal activity, which overcomes the above-mentioned drawbacks of the prior art. That is, an object of the present invention is to provide a novel nitroisourea derivative useful as an intermediate for the production of various guanidine derivatives having an insecticidal activity, and a mercaptan having a bad odor in the production process. And a method for producing a nitroguanidine derivative having insecticidal activity using the nitroisourea derivative.
[0007]
[Means for Solving the Problems]
As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that the formula (A) described in JP-A-10-120666 is an important intermediate for producing a nitroguanidine derivative having insecticidal activity. The inventors have found a nitroisourea derivative different from the isourea compound represented by the above, and found that by using the nitroisourea derivative, nitroguanidine derivatives having various insecticidal activities can be easily produced, and the present invention has been completed.
[0008]
That is, one aspect of the present invention is the formula (1)
[Chemical Formula 10]
[0009]
Further, one of the present invention is the formula (2) (Formula 11)
Embedded image
And a nitroisourea represented by the formula (3)
[0010]
Embedded image
[0011]
Furthermore, one aspect of the present invention is a nitroisourea derivative represented by the formula (1) and a formula (4)
Embedded image
[0012]
Embedded image
[0013]
DETAILED DESCRIPTION OF THE INVENTION
The present invention is described in detail below.
In the present invention, the alkyl group having 1 to 4 carbon atoms of R 1 , R 2 , R 3 , R 4 , R 5 and R 6 includes a methyl group, an ethyl group, a propyl group, an i-propyl group, a butyl group, i Examples include -butyl group and t-butyl group. In addition, as the 5-membered or 6-membered heterocyclic group which contains at least one nitrogen atom, oxygen atom or sulfur atom of Q and may be substituted with a halogen atom, a pyridyl group, pyridazyl group, pyrimidyl group, pyrazolyl group And imidazolyl group, furanyl group, tetrahydrofuranyl group, isoxazolyl group, oxazolyl group, thienyl group, tetrahydrothienyl group, thiazolyl group, isothiazolyl group and the like.
In the present invention, R 1 and R 2 are preferably each independently an alkyl group having 1 to 4 carbon atoms, R 3 is preferably a hydrogen atom, and R 4 , R 5 and R 6 are preferably a hydrogen atom. . Among these, Q is preferably a 2-chloro-5-thiazolyl group, a 2-chloro-5-pyridinyl group, or a 3-tetrahydrofuranyl group from the viewpoint of excellent insecticidal activity.
[0014]
The compound of the present invention represented by the formula (1) is a novel compound, and these can be produced by the method described in the reaction formula (1) (Chemical Formula 15).
[0015]
Embedded image
[0016]
In Scheme (1), a known amine or its salt represented by the formula (2) and the compound represented by Formula (3), in a solvent, in a pH from 7.0 9.0, preferably Can react with the pH adjusted from 7.0 to 8.0 to produce the nitroisourea derivative represented by the formula (1). When the pH is lower than 7.0, the reaction hardly proceeds, and when the pH exceeds 9.0, the desired product cannot be obtained.
[0017]
Examples of acids that form salts with amines represented by formula (3) include mineral acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid, acetic acid, propionic acid, and the like. Examples thereof include carboxylic acids.
[0018]
Solvents used in the reaction represented by the reaction formula (1) include water, alcohols such as methanol and ethanol, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-dimethyl-2-imidazolidinone. Examples thereof include aprotic polar solvents such as (DMI), ethers such as tetrahydrofuran (THF) and dioxane, nitriles such as acetonitrile and propionitrile, and ketones such as acetone.
[0019]
For the pH adjustment in the reaction represented by the reaction formula (1), acids represented by mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and alkali metals such as sodium hydroxide and potassium hydroxide are representative. A combination of bases to be used, or a buffer solution represented by a special buffer solution such as a general buffer solution such as sodium borate-hydrochloric acid, a tris-hydrochloric acid buffer solution, or a triethanolamine-hydrochloric acid buffer solution can be used. .
The amount used of the amines represented by formula (3) and salts thereof is preferably 1 to 2 equivalents, more preferably 1 to 1.1 equivalents, relative to the compound represented by formula (2).
[0020]
In the reaction formula (1), the compound represented by the formula (2) is a known compound. For example, Recl. Trav. Chim. It can be prepared by nitration of 1-methylisourea sulfate as described in Pays-Bas, 1962, 81, 69.
[0021]
The reaction temperature and reaction time for the above reaction can be varied over a wide range. In general, the reaction temperature is preferably -20 to 200 ° C, more preferably 0 to 100 ° C, and the reaction time is preferably 0.01 to 50 hours, more preferably 0.1 to 15 hours.
In the nitroisourea derivative represented by the formula (1), when R 3 is a hydrogen atom, as shown in the following formula (Formula 16), its tautomer may exist in any ratio. This isomer and mixtures thereof are also encompassed by the present invention.
[0022]
Embedded image
From the nitroisourea derivative represented by the formula (1) thus produced, a nitroguanidine derivative having an insecticidal activity represented by the formula (5) is produced by the following reaction formula (2) (chemical formula 17). can do.
[0024]
Embedded image
[0025]
In the reaction formula (2), the nitroisourea derivative represented by the formula (1) is reacted with the amine represented by the formula (4) or a salt thereof in a solvent in the absence or presence of a base. A nitroguanidine derivative having an insecticidal activity represented by formula (5) can be produced.
[0026]
Examples of the base used in the reaction represented by the reaction formula (2) include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide, and hydroxides of alkaline earth metals such as magnesium hydroxide and calcium hydroxide. Products, alkali metal hydrides such as sodium hydride and potassium hydride, alkali metal alcoholates such as sodium methoxide and sodium ethoxide, alkali metal oxides such as sodium oxide, potassium carbonate and sodium carbonate Alkali metal carbonates such as tripotassium phosphate, trisodium phosphate, dipotassium monohydrogen phosphate, disodium monohydrogen phosphate, alkali metal phosphates such as sodium acetate and potassium acetate Salts, pyridine, 4- (dimethylamino) pyridine, triethylamine, diazabicyclo It can be exemplified organic bases such as decene (DBU).
[0027]
Solvents used in the reaction represented by the reaction formula (2) include water, alcohols such as methanol, ethanol, propanol and butanol, halogenated hydrocarbons such as dichloromethane and chloroform, and aromatics such as benzene, toluene and xylene. Group hydrocarbons, dimethylformamide (DMF), dimethylacetamide (DMA), dimethylsulfoxide (DMSO), 1,3-dimethyl-2-imidazolidinone (DMI), 1-methyl-2-pyrrolidone (NMP), etc. Aprotic polar solvent, ethers such as ethyl ether, isopropyl ether, 1,2-dimethoxyethane (DME), tetrahydrofuran (THF), dioxane, nitriles such as acetonitrile and propionitrile, ketones such as acetone and isopropyl ketone List things Can. Among these, water and alcohols are particularly preferable.
[0028]
The amount used of the amines represented by formula (4) is preferably 1 to 2 equivalents, more preferably 1 to 1.2 equivalents, relative to the nitroisourea derivative represented by formula (1).
The reaction temperature and reaction time of the reaction represented by the reaction formula (2) can be varied in a wide range. In general, the reaction temperature is preferably −20 ° C. to 200 ° C., more preferably 0 to 100 ° C., and the reaction time is preferably 0.01 to 50 hours, more preferably 0.1 to 15 hours.
[0029]
In the reaction formula (2), the amines represented by the formula (4) are known compounds, for example, a method described in DE 3727126A, JP-A-5-286936, JP-A-7-179448, EP4466913A, JP-A-4-21674 and the like. Can be manufactured.
In the reaction formula (2), the acids that form salts with the amines represented by the formula (4) include mineral acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid. And carboxylic acids such as acetic acid and propionic acid.
The nitroguanidine derivative represented by the formula (5) thus obtained exhibits excellent insecticidal activity.
[0030]
【Example】
Next, the contents of the present invention will be specifically described with reference to Examples and Reference Examples, but the present invention is not limited to these.
Example 1 Production of 1,3-dimethyl-2-nitroisourea (Compound 1-1)
15 ml of water was added to 1.5 g of 1-methyl-2-nitroisourea to suspend it, and 0.9 g of methylamine hydrochloride was added thereto (pH = 3.3). A 1% sodium hydroxide aqueous solution was slowly added to the suspension aqueous solution at room temperature so as to maintain the pH at 8. The mixture was stirred at room temperature for 3 hours while maintaining the pH of the aqueous suspension, and then an aqueous hydrochloric acid solution (4M) was added, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained oil was purified by silica gel column chromatography (2: 1 hexane / ethyl acetate) and recrystallized (ethyl acetate-hexane) to give 1.0 g of the title compound as colorless crystals. .
1 H-NMR (CDCl 3 , ppm): 3.02 (3H, d, J = 4.9Hz), 3.97 (3H, s), 9.10 (1H, s)
[0031]
Example 2 Production of 1,3-dimethyl-2-nitroisourea (Compound 1-1)
1.0 g of 1-methyl-2-nitroisourea was suspended in 10 ml of tris (hydroxymethyl) aminomethane-hydrochloric acid buffer aqueous solution (Tris-hydrochloric acid buffer solution, 1.0 M, pH = 7.5). 0.6 g of amine hydrochloride was added at room temperature. After stirring for 3 hours, an aqueous hydrochloric acid solution (4M) was added, followed by extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained oil was purified by silica gel column chromatography (2: 1 hexane / ethyl acetate) and then recrystallized (ethyl acetate-hexane) to give 0.8 g of the title compound as colorless crystals. .
[0032]
Comparative Example 1
1.0 g of 1-methyl-2-nitroisourea was suspended in 10 ml of water, and 0.6 g of methylamine hydrochloride was added thereto (pH = 3.3). A 1% aqueous sodium hydroxide solution was slowly added to the suspended aqueous solution at room temperature so as to maintain the pH at 6.5. While stirring at room temperature while maintaining the pH of the aqueous suspension at 6.5, the reaction did not proceed at all.
[0033]
Comparative Example 2
1.0 g of 1-methyl-2-nitroisourea was suspended in 10 ml of water, and 0.6 g of methylamine hydrochloride was added thereto (pH = 3.3). A 1% sodium hydroxide aqueous solution was slowly added to the suspension aqueous solution at room temperature so as to maintain the pH at 6.9. While stirring at room temperature while maintaining the pH of the aqueous suspension at 6.9, the reaction did not proceed at all and the title compound was not obtained.
[0034]
Comparative Example 3
1.0 g of 1-methyl-2-nitroisourea was suspended in 10 ml of water, and 0.6 g of methylamine hydrochloride was added thereto (pH = 3.3). A 1% aqueous sodium hydroxide solution was slowly added to the suspended aqueous solution at room temperature so as to maintain a pH of 9.1. While maintaining the pH of the aqueous suspension at 9.1, the suspension was stirred at room temperature for 3 hours. After the reaction solution was extracted with dichloromethane, the organic layer was dried over anhydrous magnesium sulfate. The oil obtained by concentrating the organic layer under reduced pressure was purified by silica gel column chromatography (2: 1 hexane / ethyl acetate) and then recrystallized (ethyl acetate-hexane), but the target compound was not obtained. 1-methyl-2-nitroguanidine (0.9 g) was obtained as colorless crystals.
[0035]
The compounds that can be produced in the same manner as in Examples 1 and 2 are shown in Table 1 (Table 1). In Table 1, Me is a methyl group, Et is an ethyl group, n-Pr is an n-propyl group, i-Pr is an isopropyl group, n-Bu is an n-butyl group, and Bn is benzyl. It shall represent a group.
[0036]
[Table 1]
Example 3 Preparation of 1-[(2-chloro-5-pyridyl) methyl] -3-methyl-2-nitroguanidine (Compound 2-1) 1,3-Dimethyl-2-nitroisourea 1.0 g of methanol To the 10 ml solution, 1.28 g of [(2-chloro-5-pyridyl) methyl] amine was added and stirred at room temperature for 5 hours. The oily substance obtained by concentrating the reaction solution under reduced pressure was purified by silica gel column chromatography (ethyl acetate) and then recrystallized (methanol-ether) to obtain 1.40 g of the title compound as colorless crystals.
Example 4 Preparation of 1-[(2-chloro-5-thiazolyl) methyl] -3-methyl-2-nitroguanidine (Compound 2-2) 1.0 g of 1,3-dimethyl-2-nitroisourea in methanol To the 10 ml solution, 1.32 g of [(2-chloro-5-thiazolyl) methyl] amine was added and stirred at room temperature for 4 hours. The oily substance obtained by concentrating the reaction solution under reduced pressure was purified by silica gel column chromatography (ethyl acetate) and then recrystallized (methanol-ether) to obtain 1.11 g of the title compound as pale yellow crystals.
Example 5 Preparation of 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine To a solution of 1.0 g of 1,3-dimethyl-2-nitroisourea in 10 ml of methanol [(3-tetrahydrofuryl ) 0.91 g of methyl] amine was added and stirred at room temperature for 3 hours. The oily substance obtained by concentrating the reaction solution under reduced pressure was purified by silica gel column chromatography (ethyl acetate) and then recrystallized (methanol-ether) to obtain 1.44 g of the title compound as colorless crystals.
Example 6 Preparation of 1-[(2-chloro-5-pyridyl) methyl] -3-methyl-2-nitroguanidine (Compound 2-1) 1.0 g of 1,3-dimethyl-2-nitroisourea was added to water. The suspension was suspended in 10 ml, and 1.28 g of [(2-chloro-5-pyridyl) methyl] amine was added thereto, followed by stirring at room temperature for 3 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The oily substance obtained was purified by silica gel column chromatography (ethyl acetate) and recrystallization (methanol-ether) to give 1.23 g of the title compound colorless. As crystals of
[0041]
Example 7 Preparation of 1-[(2-chloro-5-thiazolyl) methyl] -3-methyl-2-nitroguanidine (Compound 2-2) 1.0 g of 1,3-dimethyl-2-nitroisourea was added to water. The suspension was suspended in 10 ml, and 1.32 g of [(2-chloro-5-thiazolyl) methyl] amine was added thereto, followed by stirring at room temperature for 5 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The oily substance obtained was purified by silica gel column chromatography (ethyl acetate) and recrystallization (methanol-ether) to obtain 0.95 g of the title compound. Obtained as yellow crystals.
[0042]
Example 8 Preparation of 1-methyl-2-nitro-3-[(3-tetrahydrofuryl) methyl] guanidine (Compound 2-3) 1.0 g of 1,3-dimethyl-2-nitroisourea was suspended in 10 ml of water. The mixture was made turbid, 0.91 g of [(3-tetrahydrofuryl) methyl] amine was added, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was diluted with water and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The oily substance obtained was purified by silica gel column chromatography (ethyl acetate) and recrystallization (methanol-ether) to give 1.24 g of the title compound colorless. As crystals of
The compounds that can be produced in the same manner as in Examples 3 to 8 are shown in Table 2 (Table 2, Table 3, and Table 4). In Table 2, Me represents a methyl group, Et represents an ethyl group, n-Pr represents an n-propyl group, i-Pr represents an isopropyl group, and n-Bu represents an n-butyl group. .
[0043]
[Table 2]
[Table 3]
[Table 4]
【The invention's effect】
The compound of the present invention represented by the formula (1) is a novel compound, and by reacting the present compound with various amines represented by the formula (4), a mercaptan having a bad odor is not produced as a by-product, Various nitroguanidine derivatives having insecticidal activity can be easily produced. Therefore, the compound of the present invention represented by the formula (1) can be applied as an important intermediate for producing a nitroguanidine derivative having insecticidal activity.
Claims (11)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| JP19686999A JP3720637B2 (en) | 1998-07-24 | 1999-07-12 | New nitroisourea derivatives |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP20973998 | 1998-07-24 | ||
| JP10-209739 | 1998-07-24 | ||
| JP21797498 | 1998-07-31 | ||
| JP10-217974 | 1998-07-31 | ||
| JP19686999A JP3720637B2 (en) | 1998-07-24 | 1999-07-12 | New nitroisourea derivatives |
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| AU2007213272A1 (en) | 2006-02-10 | 2007-08-16 | Mitsui Chemicals, Inc. | Process for producing O-methyl-N-nitroisourea |
| JP4966210B2 (en) * | 2006-02-10 | 2012-07-04 | 三井化学アグロ株式会社 | Improved process for producing nitroguanidine derivatives |
| ZA200806840B (en) | 2006-02-10 | 2010-01-27 | Mitsui Chemicals Inc | Improved process for producing nitroisourea derivatives |
| EP1997802A4 (en) * | 2006-03-16 | 2011-05-25 | Sumitomo Chemical Co | Method for nitrating isourea |
| CN102432561A (en) * | 2011-07-06 | 2012-05-02 | 山东京蓬生物药业股份有限公司 | Method for preparing neonicotine pesticide clothianidin |
| JP6067362B2 (en) * | 2012-12-18 | 2017-01-25 | 花王株式会社 | Urinary absorbent for small animals for toilets |
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