JP4788698B2 - CARBOXYLIC ACID DERIVATIVE, PROCESS FOR PRODUCING THE SAME AND PROCESS FOR PRODUCING PYRIZAZN-3-ONE DERIVATIVE USING THE SAME - Google Patents

Description

The present invention relates to a carboxylic acid derivative, a process for producing the same, and a process for producing a pyridazin-3-one derivative using the same.

で示されるようなピリダジン−３−オン誘導体は、優れた除草活性を有しており、これらのピリダジン−３−オン誘導体の有利な製造方法の開発が望まれていた。 Formula 8
[ Chemical formula 8 ]

The pyridazin-3-one derivatives as shown by the above have excellent herbicidal activity, and development of an advantageous production method of these pyridazin-3-one derivatives has been desired.

[式中、Ｒ²は水素原子またはＣ１−Ｃ３アルキル基を表し、Ｒ³は水素原子またはＣ１−Ｃ３アルキル基を表し、Ｑは置換されていてもよいフェニル基を表す。]で示されるカルボン酸誘導体またはその塩が、前記の式 化８で示されるピリダジン-３-オン誘導体等に導けることから、その重要な中間体であることを見出し、本発明に至った。
即ち、本発明は、一般式 化９で示される化合物（以下、本発明化合物−１と記す）、本発明化合物−１の塩（以下、本発明化合物−２と記す）（尚、以下、本発明化合物−１と本発明化合物−２をあわせて、本発明化合物と総称する）、本発明化合物−１の製造法、及び本発明化合物−１から一般式 化１０
〔化１０〕

[式中、Ｑ、Ｒ²およびＲ³は前記と同じ意味を表す。]
で示されるピリダジン-３-オン誘導体を製造する製造法を提供する。 As a result of intensive studies to find an advantageous production method of the pyridazin-3-one derivative, the present inventor has
[ Chemical 9 ]

[Wherein R ² represents a hydrogen atom or a C1-C3 alkyl group, R ³ represents a hydrogen atom or a C1-C3 alkyl group, and Q represents an optionally substituted phenyl group. The carboxylic acid derivative represented by the formula (1) or a salt thereof can be converted to the pyridazin-3-one derivative represented by the above formula 8 and the like, so that the present invention was found to be an important intermediate.
That is, the present invention includes a compound represented by the general formula 9 (hereinafter referred to as the present compound-1), a salt of the present compound-1 (hereinafter referred to as the present compound-2) (hereinafter referred to as the present invention). Inventive Compound-1 and Inventive Compound-2 are collectively referred to as Inventive Compound), a production method of Inventive Compound-1, and General Formula 10
[ Chemical formula 10 ]

[Wherein, Q, R ² and R ³ represent the same meaning as described above. ]
The manufacturing method which manufactures the pyridazin-3-one derivative shown by these is provided.

  According to the present invention, a pyridazin-3-one derivative represented by the general formula 10 can be easily produced.

［式中、Ｘは水素原子またはハロゲン原子を表し、Ｙはハロゲン原子、ニトロ基、シアノ基またはトリフルオロメチル基を表し、Ｚ¹およびＺ²はそれぞれ酸素原子または硫黄原子を表し、
ｎは０または１を表し、
Ｒ⁴は水素原子またはＣ１−Ｃ３アルキル基を表し、
Ｒ⁵はＣ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、（Ｃ３−Ｃ８シクロアルキル）Ｃ１−Ｃ６アルキル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ６ハロアルケニル基、Ｃ３−Ｃ６アルキニル基、Ｃ３−Ｃ６ハロアルキニル基、シアノＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル基、（Ｃ１−Ｃ３アルコキシ）（Ｃ１−Ｃ３アルコキシ）Ｃ１−Ｃ３アルキル基、カルボキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、｛（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルコキシ｝カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルコキシ）カルボニルＣ１−Ｃ６アルキル基、−ＣＨ₂ＣＯＮ（Ｒ¹²）Ｒ¹³基、−ＣＨ₂ＣＯＯＮ（Ｒ¹²）Ｒ¹³基、−ＣＨ（Ｃ１−Ｃ４アルキル）ＣＯＮ（Ｒ¹²）Ｒ¹³基、−ＣＨ（Ｃ１−Ｃ４アルキル）ＣＯＯＮ（Ｒ¹²）Ｒ¹³基（ここで、Ｒ¹²およびＲ¹³はそれぞれ独立して水素原子、Ｃ１−Ｃ６アルキル基、Ｃ３−Ｃ８シクロアルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ６アルキニル基、シアノＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル基、（Ｃ１−Ｃ４アルキルチオ）Ｃ１−Ｃ４アルキル基、カルボキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルキル）カルボニルオキシＣ２−Ｃ６アルキル基、（Ｃ１−Ｃ６アルキル）カルボニルアミノＣ２−Ｃ６アルキル基、ヒドロキシＣ２−Ｃ６アルキル基、置換されていてもよいベンジル基、置換されていてもよいフェニル基または｛（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル｝カルボニルＣ１−Ｃ６アルキルを表すか、あるいは、Ｒ¹²とＲ¹³とでトリメチレン、テトラメチレン、ペンタメチレン、エチレンオキシエチレンまたはエチレンチオエチレンを表す。）、（Ｃ１−Ｃ４アルキルチオ）Ｃ１−Ｃ４アルキル基またはヒドロキシＣ１−Ｃ６アルキル基を表し、
Ｒ⁶はＣ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、シアノ基、カルボキシル基、ヒドロキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルコキシ）Ｃ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルコキシ）（Ｃ１−Ｃ６アルコキシ）Ｃ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルキル）カルボニルオキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６ハロアルキル）カルボニルオキシＣ１−Ｃ６アルキル基または（Ｃ１−Ｃ６アルコキシ）カルボニル基を表し、
Ｒ⁷ は水素原子またはＣ１−Ｃ６アルキル基を表し、
Ｒ⁸はＣ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、ヒドロキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル基、（Ｃ１−Ｃ３アルコキシ）（Ｃ１−Ｃ３アルコキシ）Ｃ１−Ｃ３アルキル基、（Ｃ１−Ｃ６アルキル）カルボニルオキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６ハロアルキル）カルボニルＣ１−Ｃ６アルキル基、カルボキシ基、カルボキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ８アルコキシ）カルボニル基、（Ｃ１−Ｃ６ハロアルコキシ）カルボニル基、（Ｃ３−Ｃ１０シクロアルコキシ）カルボニル基、（Ｃ３−Ｃ８アルケニルオキシ）カルボニル基、（Ｃ３−Ｃ８アルキニルオキシ）カルボニル基、（Ｃ１−Ｃ６アルキル）アミノカルボニル基、ジ（Ｃ１−Ｃ６アルキル）アミノカルボニル基、（Ｃ１−Ｃ６アルキル）アミノカルボニルオキシＣ１−Ｃ６アルキル基またはジ（Ｃ１−Ｃ６アルキル）アミノカルボニルオキシＣ１−Ｃ６アルキル基を表し、
Ｂは、水素原子、ハロゲン原子、ニトロ基、シアノ基、クロロスルホニル基、ＯＲ¹基、ＳＲ¹基、ＳＯ₂ＯＲ²¹基、ＣＯＯＲ²²基、ＣＲ²³＝ＣＲ²⁴ＣＯＯＲ²⁵基またはＣＨ₂ＣＨＷＣＯＯＲ²⁵基を表わす。
{ここでＷは水素原子、塩素原子、または、臭素原子を表し、
Ｒ¹は水素原子、Ｃ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ８シクロアルキル基、ベンジル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ６ハロアルケニル基、Ｃ３−Ｃ６アルキニル基、Ｃ３−Ｃ６ハロアルキニル基、シアノＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル基、（Ｃ１−Ｃ４アルキルチオ）Ｃ１−Ｃ４アルキル基、カルボキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ８アルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６ハロアルコキシ）カルボニルＣ１−Ｃ６アルキル基、｛（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルコキシ｝カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルキル）（Ｃ１−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、−ＣＨ₂ＣＯＯＮ（Ｒ¹²）Ｒ¹³基、−ＣＨ（Ｃ１−Ｃ４アルキル）ＣＯＯＮ（Ｒ¹²）Ｒ¹³基、−ＣＨ₂ＣＯＮ（Ｒ¹²）Ｒ¹³基、−ＣＨ（Ｃ１−Ｃ４アルキル）ＣＯＮ（Ｒ¹²）Ｒ¹³基
（ここで、Ｒ¹²とＲ¹³は前記と同じ意味を表す。）、
（Ｃ２−Ｃ６アルケニル）オキシカルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ６ハロアルケニル）オキシカルボニルＣ１−Ｃ６アルキル基、
（Ｃ３−Ｃ６アルキニル）オキシカルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ６ハロアルキニル）オキシカルボニルＣ１−Ｃ６アルキル基、
（Ｃ１−Ｃ６アルキルチオ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６ハロアルキルチオ）カルボニルＣ１−Ｃ６アルキル基、
（Ｃ３−Ｃ６アルケニルチオ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ６ハロアルケニルチオ）カルボニルＣ１−Ｃ６アルキル基、
（Ｃ３−Ｃ６アルキニルチオ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ６ハロアルキニルチオ）カルボニルＣ１−Ｃ６アルキル基、
（Ｃ３−Ｃ８シクロアルキルチオ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロハロアルキルチオ）カルボニルＣ１−Ｃ６アルキル基、
（（Ｃ３−Ｃ８シクロアルキル）Ｃ１−Ｃ６アルキルチオ）カルボニルＣ１−Ｃ６アルキル基、
ジ（Ｃ１−Ｃ６アルキル）Ｃ＝ＮＯカルボニルＣ１−Ｃ６アルキル基、
（置換されていてもよいベンジルチオ）カルボニルＣ１−Ｃ６アルキル基、（置換されていてもよいフェニルチオ）カルボニルＣ１−Ｃ６アルキル基、
ヒドロキシ（Ｃ２−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、
（Ｃ１−Ｃ６アルキル）カルボニルオキシ（Ｃ２−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、
（Ｃ１−Ｃ６アルキル）カルボニルアミノ（Ｃ２−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、
｛（Ｃ１−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル｝オキシカルボニルＣ１−Ｃ６アルキル基、ヒドロキシＣ１−Ｃ６アルキル基、Ｃ１−Ｃ６アルコキシカルボニル基、Ｃ１−Ｃ６ハロアルコキシカルボニル基、Ｃ３−Ｃ８シクロアルコキシカルボニル基、Ｃ３−Ｃ６アルケニルオキシカルボニル基、ベンジルオキシカルボニル基、Ｃ１−Ｃ６アルキルカルボニル基、
置換されていてもよいベンジルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいフェノキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいフリルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいフリル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいチエニルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいチエニル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいピロリルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいピロリルオキシ（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいイミダゾイルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいイミダゾイル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいピラゾイルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいピラゾイル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいチアゾイルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいチアゾイル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいオキサゾイルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいオキサゾイル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいイソチアゾイルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいイソチアゾイル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいイソキサゾイルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいイソキサゾイル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいピリジルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいピリジル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいピラジニルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいピラジニル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいピリミジニルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいピリミジニル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいピリダジニルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいピリダジニル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいインドリジニルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいインドリジニル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいインドリルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいインドリル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいインダゾリルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいインダゾリル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいキノリルオキシカルボニルＣ１−Ｃ６アルキル基、置換されていてもよいキノリル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基、
置換されていてもよいイソキノリルオキシカルボニルＣ１−Ｃ６アルキル基、または置換されていてもよいイソキノリル（Ｃ１−Ｃ６アルキル）オキシカルボニルＣ１−Ｃ６アルキル基を表すか、
一般式 化１２
〔化１２〕

{式中、Ｒ¹⁴はＣ１−Ｃ５アルキル基を表し、Ｒ¹⁵は水素原子、ヒドロキシル基または−Ｏ−ＣＯＲ¹⁶で表される基（Ｒ¹⁶は、Ｃ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ８シクロアルキル基、置換されていてもよいフェニル基、置換されていてもよいベンジル基、またはＣ１−Ｃ６アルコキシ基を表す。）を表す。}
で示される基を表すか、あるいは、一般式 化１３
〔化１３〕

〈式中、Ｒ¹⁷は水素原子、ハロゲン原子またはＣ１−Ｃ６アルキル基を表し、
Ｒ¹⁸はＣ３−Ｃ８シクロアルキル基、ベンジル基、炭素鎖にエポキシ基を有するＣ２−Ｃ１０アルキル基、（Ｃ３−Ｃ８シクロアルキル）Ｃ１−Ｃ６アルキル基、
（Ｃ３−Ｃ８シクロアルキル）Ｃ２−Ｃ６アルケニル基、
同一の炭素原子がＯＲ¹⁹およびＯＲ²⁰で置換されたＣ１−Ｃ６アルキル基、
同一の炭素原子がＯＲ¹⁹およびＯＲ²⁰で置換されたＣ２−Ｃ６アルケニル基、
同一の炭素原子がＳＲ¹⁹およびＳＲ²⁰で置換されたＣ１−Ｃ６アルキル基、
同一の炭素原子がＳＲ¹⁹およびＳＲ²⁰で置換されたＣ２−Ｃ６アルケニル基
（ここでＲ¹⁹とＲ²⁰はそれぞれ独立してＣ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基を表すか、Ｒ¹⁹とＲ²⁰とで、ハロゲン原子で置換されていてもよいエチレン、ハロゲン原子で置換されていてもよいトリメチレン、ハロゲン原子で置換されていてもよいテトラメチレン、ハロゲン原子で置換されていてもよいペンタメチレンまたはハロゲン原子で置換されていてもよいエチレンオキシエチレンを表す。）、
カルボキシＣ２−Ｃ６アルケニル基、
（Ｃ１−Ｃ８アルコキシ）カルボニルＣ２−Ｃ６アルケニル基、
（Ｃ１−Ｃ８ハロアルコキシ）カルボニルＣ２−Ｃ６アルケニル基、
｛（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルコキシ｝カルボニルＣ２−Ｃ６アルケニル基、または、
（Ｃ３−Ｃ８シクロアルコキシ）カルボニルＣ２−Ｃ６アルケニル基を表す。〉で示される基を表し、
Ｒ²¹はＣ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ８シクロアルキル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ６ハロアルケニル基、Ｃ３−Ｃ６アルキニル基、Ｃ３−Ｃ６ハロアルキニル基またはベンジル基を表し、
Ｒ²²は水素原子、Ｃ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ８シクロアルキル基、ベンジル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ６ハロアルケニル基、Ｃ３−Ｃ６アルキニル基、Ｃ３−Ｃ６ハロアルキニル基、
シアノＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル基、（Ｃ１−Ｃ４アルキルチオ）Ｃ１−Ｃ４アルキル基、カルボキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ８アルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６ハロアルコキシ）カルボニルＣ１−Ｃ６アルキル基、｛（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルコキシ｝カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルキル）カルボニルＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６ハロアルキル）カルボニルＣ１−Ｃ６アルキル基、{（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル}カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルキル）カルボニルＣ１−Ｃ６アルキル基、−ＣＨ₂ＣＯＯＮ（Ｒ²⁶）Ｒ²⁷基、−ＣＨ（Ｃ１−Ｃ４アルキル）ＣＯＯＮ（Ｒ²⁶）Ｒ²⁷基、−ＣＨ₂ＣＯＮ（Ｒ²⁶）Ｒ²⁷基、−ＣＨ（Ｃ１−Ｃ４アルキル）ＣＯＮ（Ｒ²⁶）Ｒ²⁷基
（ここで、Ｒ²⁶とＲ²⁷はそれぞれ独立して水素原子、Ｃ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ６アルケニル基、Ｃ３−Ｃ６アルキニル基、シアノＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル基、（Ｃ１−Ｃ４アルキルチオ）Ｃ１−Ｃ４アルキル基、カルボキシＣ１−Ｃ６アルキル基、（Ｃ１−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル基、（Ｃ３−Ｃ８シクロアルコキシ）カルボニルＣ１−Ｃ６アルキル基または、｛（Ｃ１−Ｃ４アルコキシ）Ｃ１−Ｃ４アルキル｝カルボニルＣ１−Ｃ６アルキルを表すか、あるいは、Ｒ²⁶とＲ²⁷とでテトラメチレン、ペンタメチレン、またはエチレンオキシエチレンを表す。）、
{（Ｃ１−Ｃ６アルコキシ）カルボニルＣ１−Ｃ６アルキル}オキシカルボニルＣ１−Ｃ６アルキル基、またはヒドロキシＣ１−Ｃ６アルキル基を表し、
Ｒ²³およびＲ²⁴は、それぞれ独立して、水素原子、ハロゲン原子またはＣ１−Ｃ６アルキル基を表し、
Ｒ²⁵は水素原子、Ｃ１−Ｃ６アルキル基、Ｃ１−Ｃ６ハロアルキル基、Ｃ３−Ｃ８シクロアルキル基またはＣ３−Ｃ６アルケニル基を表す。}] Here, the optionally substituted phenyl group represented by Q is, for example, a Q-1, Q-2, Q-3, Q-4 or Q-5 group represented by the following general formula 11 can give.
[ Chemical Formula 11 ]

[Wherein, X represents a hydrogen atom or a halogen atom, Y represents a halogen atom, a nitro group, a cyano group or a trifluoromethyl group, Z ¹ and Z ² each represents an oxygen atom or a sulfur atom,
n represents 0 or 1,
R ⁴ represents a hydrogen atom or a C1-C3 alkyl group,
R ⁵ is a C1-C6 alkyl group, a C1-C6 haloalkyl group, a (C3-C8 cycloalkyl) C1-C6 alkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 Haloalkynyl group, cyano C1-C6 alkyl group, (C1-C4 alkoxy) C1-C4 alkyl group, (C1-C3 alkoxy) (C1-C3 alkoxy) C1-C3 alkyl group, carboxy C1-C6 alkyl group, (C1 -C6 alkoxy) carbonyl C1-C6 alkyl group, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group, (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl group, -CH ₂ CON (R ¹²⁾ R ^{13 _{group, -CH 2 COON (R 12)}} R 13 group, -CH (C1-C4 al Kill) CON (R ¹² ) R ¹³ group, —CH (C 1 -C 4 alkyl) COON (R ¹² ) R ¹³ group (wherein R ¹² and R ¹³ are each independently a hydrogen atom, C1-C6 alkyl group, C3-C8 cycloalkyl group, C1-C6 haloalkyl group, C3-C6 alkenyl group, C3-C6 alkynyl group, cyano C1-C6 alkyl group, (C1-C4 alkoxy) C1-C4 alkyl group, (C1-C4 alkylthio) C1-C4 alkyl group, carboxy C1-C6 alkyl group, (C1-C6 alkoxy) carbonyl C1-C6 alkyl group, (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl group, (C1-C6 alkyl) carbonyloxy C2- C6 alkyl group, (C1-C6 alkyl) carbonylamino C2-C6 alkyl group, hydroxy C2-C Alkyl group, an optionally substituted benzyl group, substituted or also a phenyl group {(C1-C4 alkoxy) C1-C4 alkyl} carbonyl C1-C6 or represents alkyl, or an R ¹² and R ¹³ Represents trimethylene, tetramethylene, pentamethylene, ethyleneoxyethylene or ethylenethioethylene), (C1-C4 alkylthio) C1-C4 alkyl group or hydroxy C1-C6 alkyl group,
R ⁶ is a C1-C6 alkyl group, a C1-C6 haloalkyl group, a cyano group, a carboxyl group, a hydroxy C1-C6 alkyl group, a (C1-C6 alkoxy) C1-C6 alkyl group, (C1-C6 alkoxy) (C1-C6 An alkoxy) C1-C6 alkyl group, a (C1-C6 alkyl) carbonyloxy C1-C6 alkyl group, a (C1-C6 haloalkyl) carbonyloxy C1-C6 alkyl group or a (C1-C6 alkoxy) carbonyl group,
R ⁷ represents a hydrogen atom or a C1-C6 alkyl group,
R ⁸ is a C1-C6 alkyl group, a C1-C6 haloalkyl group, a hydroxy C1-C6 alkyl group, a (C1-C4 alkoxy) C1-C4 alkyl group, a (C1-C3 alkoxy) (C1-C3 alkoxy) C1-C3 alkyl. Group, (C1-C6 alkyl) carbonyloxy C1-C6 alkyl group, (C1-C6 haloalkyl) carbonyl C1-C6 alkyl group, carboxy group, carboxy C1-C6 alkyl group, (C1-C8 alkoxy) carbonyl group, (C1 -C6 haloalkoxy) carbonyl group, (C3-C10 cycloalkoxy) carbonyl group, (C3-C8 alkenyloxy) carbonyl group, (C3-C8 alkynyloxy) carbonyl group, (C1-C6 alkyl) aminocarbonyl group, di ( C1-C6 alkyl) aminocarbonyl group, It represents C1-C6 alkyl) aminocarbonyloxy C1-C6 alkyl group or a di (C1-C6 alkyl) aminocarbonyloxy C1-C6 alkyl group,
B is a hydrogen atom, halogen atom, nitro group, cyano group, chlorosulfonyl group, OR ¹ group, SR ¹ group, SO ₂ OR ²¹ group, COOR ²² group, CR ²³ = CR ²⁴ COOR ²⁵ group or CH ₂ CHWCOOR ²⁵ Represents a group.
{W represents a hydrogen atom, a chlorine atom, or a bromine atom,
R ¹ is a hydrogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C3-C8 cycloalkyl group, benzyl group, C3-C6 alkenyl group, C3-C6 haloalkenyl group, C3-C6 alkynyl group, C3-C6. Haloalkynyl group, cyano C1-C6 alkyl group, (C1-C4 alkoxy) C1-C4 alkyl group, (C1-C4 alkylthio) C1-C4 alkyl group, carboxy C1-C6 alkyl group, (C1-C8 alkoxy) carbonyl C1 -C6 alkyl group, (C1-C6 haloalkoxy) carbonyl C1-C6 alkyl group, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group, (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl Group (C3-C8 cycloalkyl) (C1-C6 Shi) carbonyl C1-C6 alkyl ^{_{group, -CH 2 COON (R 12)}} R 13 group, -CH (C1-C4 alkyl) COON (R ¹²⁾ R ^{13 _{group, -CH 2 CON (R 12)}} R 13 group, -CH (C1-C4 alkyl) CON (R ¹²⁾ R ¹³ group (herein, R ¹² and R ¹³ are as defined above.)
(C2-C6 alkenyl) oxycarbonyl C1-C6 alkyl group, (C3-C6 haloalkenyl) oxycarbonyl C1-C6 alkyl group,
(C3-C6 alkynyl) oxycarbonyl C1-C6 alkyl group, (C3-C6 haloalkynyl) oxycarbonyl C1-C6 alkyl group,
(C1-C6 alkylthio) carbonyl C1-C6 alkyl group, (C1-C6 haloalkylthio) carbonyl C1-C6 alkyl group,
(C3-C6 alkenylthio) carbonyl C1-C6 alkyl group, (C3-C6 haloalkenylthio) carbonyl C1-C6 alkyl group,
(C3-C6 alkynylthio) carbonyl C1-C6 alkyl group, (C3-C6 haloalkynylthio) carbonyl C1-C6 alkyl group,
(C3-C8 cycloalkylthio) carbonyl C1-C6 alkyl group, (C3-C8 cyclohaloalkylthio) carbonyl C1-C6 alkyl group,
((C3-C8 cycloalkyl) C1-C6 alkylthio) carbonyl C1-C6 alkyl group,
Di (C1-C6 alkyl) C = NO carbonyl C1-C6 alkyl group,
(Optionally substituted benzylthio) carbonyl C1-C6 alkyl group, (optionally substituted phenylthio) carbonyl C1-C6 alkyl group,
A hydroxy (C2-C6 alkoxy) carbonyl C1-C6 alkyl group,
(C1-C6 alkyl) carbonyloxy (C2-C6 alkoxy) carbonyl C1-C6 alkyl group,
(C1-C6 alkyl) carbonylamino (C2-C6 alkoxy) carbonyl C1-C6 alkyl group,
{(C1-C6 alkoxy) carbonyl C1-C6 alkyl} oxycarbonyl C1-C6 alkyl group, hydroxy C1-C6 alkyl group, C1-C6 alkoxycarbonyl group, C1-C6 haloalkoxycarbonyl group, C3-C8 cycloalkoxycarbonyl group C3-C6 alkenyloxycarbonyl group, benzyloxycarbonyl group, C1-C6 alkylcarbonyl group,
An optionally substituted benzyloxycarbonyl C1-C6 alkyl group, an optionally substituted phenoxycarbonyl C1-C6 alkyl group,
An optionally substituted furyloxycarbonyl C1-C6 alkyl group, an optionally substituted furyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted thienyloxycarbonyl C1-C6 alkyl group, an optionally substituted thienyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted pyrrolyloxycarbonyl C1-C6 alkyl group, an optionally substituted pyrrolyloxy (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted imidazolyloxycarbonyl C1-C6 alkyl group, an optionally substituted imidazolyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted pyrazoyloxycarbonyl C1-C6 alkyl group, an optionally substituted pyrazoyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted thiazoyloxycarbonyl C1-C6 alkyl group, an optionally substituted thiazoyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted oxazoyloxycarbonyl C1-C6 alkyl group, an optionally substituted oxazoyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted isothiazoyloxycarbonyl C1-C6 alkyl group, an optionally substituted isothiazoyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted isoxazoyloxycarbonyl C1-C6 alkyl group, an optionally substituted isoxazoyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted pyridyloxycarbonyl C1-C6 alkyl group, an optionally substituted pyridyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted pyrazinyloxycarbonyl C1-C6 alkyl group, an optionally substituted pyrazinyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted pyrimidinyloxycarbonyl C1-C6 alkyl group, an optionally substituted pyrimidinyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted pyridazinyloxycarbonyl C1-C6 alkyl group, an optionally substituted pyridazinyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted indolizinyloxycarbonyl C1-C6 alkyl group, an optionally substituted indolizinyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted indolyloxycarbonyl C1-C6 alkyl group, an optionally substituted indolyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
An optionally substituted indazolyloxycarbonyl C1-C6 alkyl group, an optionally substituted indazolyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
Optionally substituted quinolyloxycarbonyl C1-C6 alkyl group, optionally substituted quinolyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
Represents an optionally substituted isoquinolyloxycarbonyl C1-C6 alkyl group, or an optionally substituted isoquinolyl (C1-C6 alkyl) oxycarbonyl C1-C6 alkyl group,
General formula
[ Chemical formula 12 ]

{Wherein R ¹⁴ represents a C1-C5 alkyl group, R ¹⁵ represents a hydrogen atom, a hydroxyl group or a group represented by —O—COR ¹⁶ (R ¹⁶ represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, Represents a C3-C6 alkenyl group, a C3-C8 cycloalkyl group, an optionally substituted phenyl group, an optionally substituted benzyl group, or a C1-C6 alkoxy group. }
Or a group represented by the general formula:
[ Chemical 13 ]

<In the formula, R ¹⁷ represents a hydrogen atom, a halogen atom or a C1-C6 alkyl group;
R ¹⁸ is a C3-C8 cycloalkyl group, a benzyl group, a C2-C10 alkyl group having an epoxy group on the carbon chain, a (C3-C8 cycloalkyl) C1-C6 alkyl group,
(C3-C8 cycloalkyl) C2-C6 alkenyl group,
Same C1-C6 alkyl group in which the carbon atom is substituted with OR ¹⁹ and OR ^20,
A C2-C6 alkenyl group in which the same carbon atom is substituted with OR ¹⁹ and OR ²⁰ ;
A C1-C6 alkyl group in which the same carbon atom is substituted with SR ¹⁹ and SR ²⁰ ;
Same C2-C6 alkenyl group in which the carbon atom is substituted with SR ¹⁹ and SR ²⁰ (wherein R ¹⁹ and R ²⁰ are each independently C1-C6 alkyl group, or represents a C1-C6 haloalkyl group, a R ¹⁹ R ²⁰ , ethylene optionally substituted with a halogen atom, trimethylene optionally substituted with a halogen atom, tetramethylene optionally substituted with a halogen atom, pentamethylene optionally substituted with a halogen atom Or ethyleneoxyethylene optionally substituted with a halogen atom).
A carboxy C2-C6 alkenyl group,
(C1-C8 alkoxy) carbonyl C2-C6 alkenyl group,
(C1-C8 haloalkoxy) carbonyl C2-C6 alkenyl group,
{(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C2-C6 alkenyl group, or
A (C3-C8 cycloalkoxy) carbonyl C2-C6 alkenyl group is represented. Represents a group represented by
R ²¹ represents a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C8 cycloalkyl group, a C3-C6 alkenyl group, a C3-C6 haloalkenyl group, a C3-C6 alkynyl group, a C3-C6 haloalkynyl group or a benzyl group. Represents
R ²² is a hydrogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C3-C8 cycloalkyl group, benzyl group, C3-C6 alkenyl group, C3-C6 haloalkenyl group, C3-C6 alkynyl group, C3-C6 A haloalkynyl group,
Cyano C1-C6 alkyl group, (C1-C4 alkoxy) C1-C4 alkyl group, (C1-C4 alkylthio) C1-C4 alkyl group, carboxy C1-C6 alkyl group, (C1-C8 alkoxy) carbonyl C1-C6 alkyl group , (C1-C6 haloalkoxy) carbonyl C1-C6 alkyl group, {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group, (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl group, (C1 -C6 alkyl) carbonyl C1-C6 alkyl group, (C1-C6 haloalkyl) carbonyl C1-C6 alkyl group, {(C1-C4 alkoxy) C1-C4 alkyl} carbonyl C1-C6 alkyl group, (C3-C8 cycloalkyl) Carbonyl C1-C6 alkyl group, —CH ₂ COON (R ²⁶ ) R ²⁷ group, —CH (C 1 -C 4 alkyl) COON (R ²⁶ ) R ²⁷ group, —CH ₂ CON (R ²⁶ ) R ²⁷ group, —CH (C 1 -C 4 alkyl) CON (R ²⁶ ) R ²⁷ group (herein, R ²⁶ and R ²⁷ are each independently hydrogen atom, C1-C6 alkyl group, C1-C6 haloalkyl group, C3-C6 alkenyl group, C3-C6 alkynyl group, cyano C1-C6 alkyl Group, (C1-C4 alkoxy) C1-C4 alkyl group, (C1-C4 alkylthio) C1-C4 alkyl group, carboxy C1-C6 alkyl group, (C1-C6 alkoxy) carbonyl C1-C6 alkyl group, (C3-C8) A cycloalkoxy) carbonyl C1-C6 alkyl group or {(C1-C4 alkoxy) C1-C4 alkyl} carbonyl C1-C6 alkyl, There is expressed tetramethylene between R ²⁶ and R ^27, pentamethylene or ethyleneoxyethylene.),
{(C1-C6 alkoxy) carbonyl C1-C6 alkyl} represents an oxycarbonyl C1-C6 alkyl group, or a hydroxy C1-C6 alkyl group,
R ²³ and R ²⁴ each independently represents a hydrogen atom, a halogen atom or a C1-C6 alkyl group,
R ²⁵ represents a hydrogen atom, a C1-C6 alkyl group, a C1-C6 haloalkyl group, a C3-C8 cycloalkyl group or a C3-C6 alkenyl group. }]

In the compound of the present invention,
The halogen atom represented by X and Y means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom,
Examples of the C1-C3 alkyl group represented by R ² and R ³ include a methyl group and an ethyl group.
Examples of the C1-C6 alkyl group represented by R ¹ include a methyl group, an ethyl group, a propyl group, an isopropyl group, an isobutyl group, a butyl group, and a t-butyl group (where “t” represents [tertiary]: The same shall apply hereinafter), amyl groups, isoamyl groups, t-amyl groups, etc.
Examples of the C1-C6 haloalkyl group include 2-chloroethyl group, 2-bromoethyl group, 2,2,2-trifluoroethyl group, and the like.
Examples of the C3-C8 cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and the like.
As C3-C6 alkenyl group, allyl group, methallyl group, 1-methyl-2-propenyl group, 3-butenyl group, 2-butenyl group, 3-methyl-2-butenyl group, 2-methyl-3-butenyl group Etc.
Examples of the C3-C6 haloalkenyl group include 2-chloro-2-propenyl group and 3,3-dichloro-2-propenyl group.
Examples of the C3-C6 alkynyl group include propargyl group, 1-methyl-2-propynyl group, 2-butynyl group, 1,1-dimethyl-2-propynyl group,
Examples of the C3-C6 haloalkynyl group include 3-bromopropargyl group,
Examples of the cyano C1-C6 alkynyl group include a cyanomethyl group.
(C1-C4 alkoxy) Examples of the C1-C4 alkyl group include a methoxymethyl group, a methoxyethyl group, an ethoxymethyl group, an ethoxyethyl group,
(C1-C4 alkylthio) Examples of the C1-C4 alkyl group include a methylthiomethyl group, a methylthioethyl group, and the like.
Examples of the carboxy C1-C6 alkyl group include a carboxymethyl group, a 1-carboxyethyl group, a 2-carboxyethyl group, and the like.
(C1-C8 alkoxy) carbonyl C1-C6 alkyl group includes methoxycarbonylmethyl group, ethoxycarbonylmethyl group, propoxycarbonylmethyl group, isopropoxycarbonylmethyl group, butoxycarbonylmethyl group, isobutoxycarbonylmethyl group, t-butoxy Carbonylmethyl group, amyloxycarbonylmethyl group, isoamyloxycarbonylmethyl group, t-amyloxycarbonylmethyl group, 1-methoxycarbonylethyl group, 1-ethoxycarbonylethyl group, 1-propoxycarbonylethyl group, 1-isopropoxycarbonyl Ethyl group, 1-butoxycarbonylethyl group, 1-isobutoxycarbonylethyl group, 1-t-butoxycarbonylethyl group, 1-amyloxycarbonylethyl group, 1-isoa Oxy carbonyl ethyl group, 1-t-butoxycarbonyl ethyl group, 1-amyloxycarbonyl ethyl, 1-isoamyl butyloxycarbonylethyl group, such as 1-t-amyloxycarbonyl ethyl group and the like,
Examples of {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group include methoxymethoxycarbonylmethyl group, methoxyethoxycarbonylmethyl group, 1-methoxyethoxycarbonylethyl group, and the like.
The (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl group includes a cyclobutyloxycarbonylmethyl group, a cyclopentyloxycarbonylmethyl group, a cyclohexyloxycarbonylmethyl group, a 1-cyclobutyloxycarbonylethyl group, and a 1-cyclopentyloxycarbonylethyl group. Group, 1-cyclohexyloxycarbonylethyl group and the like,
Examples of the C1-C6 alkoxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group, an isopropoxycarbonyl group, an isobutoxycarbonyl group, or a t-butoxycarbonyl group.
Examples of the C1-C6 haloalkoxycarbonyl group include a 2,2,2-trichloroethylcarbonyl group and the like.
Examples of the C3-C8 cycloalkoxycarbonyl group include a cyclopropyloxycarbonyl group, a cyclobutyloxycarbonyl group, and the like.
Examples of the C3-C6 alkenyloxycarbonyl group include an allyloxycarbonyl group.
{(C1-C6 alkoxy) carbonyl C1-C6 alkyl} Examples of oxycarbonyl C1-C6 alkyl groups include (methoxycarbonyl) methoxycarbonylmethyl group, (ethoxycarbonyl) methoxycarbonylmethyl group, and the like, and R ¹² and R ¹³ Examples of the C1-C6 alkyl group represented by: include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
Examples of the C1-C3 alkyl group represented by R ⁴ include a methyl group,
Examples of the C1-C6 alkyl group represented by R ⁵ include a methyl group, an ethyl group, a propyl group, an isopropyl group, an isobutyl group, a butyl group, and an isoamyl group.
Examples of the C1-C6 haloalkyl group include 2-chloroethyl group, 2-bromoethyl group, 3-chlorobutyl group, 3-bromobutyl group, difluoromethyl group, and the like.
(C3-C8 cycloalkyl) Examples of the C1-C6 alkyl group include a cyclopentylmethyl group.
Examples of the C3-C6 alkenyl group include an allyl group, a 1-methyl-2-propenyl group, a 3-butenyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and a 2-methyl-3-butenyl group. And
Examples of the C3-C6 haloalkenyl group include 2-chloro-2-propenyl group and 3,3-dichloro-2-propenyl group.
Examples of the C3-C6 alkynyl group include propargyl group, 1-methyl-2-propynyl group, 2-butynyl group, 3-butynyl group, 1,1-dimethyl-2-propynyl group, and the like.
Examples of the C3-C6 haloalkynyl group include 3-iodo-2-propynyl group and 3-bromo-2-propynyl group.
Examples of the cyano C1-C6 alkyl group include a cyanomethyl group.
(C1-C4 alkoxy) Examples of the C1-C4 alkyl group include a methoxymethyl group, a 1-methoxyethyl group, an ethoxymethyl group, and the like.
Examples of the carboxy C1-C6 alkyl group include a carboxymethyl group, a 1-carboxyethyl group, a 2-carboxyethyl group, and the like.
(C1-C6 alkoxy) carbonyl C1-C6 alkyl group includes methoxycarbonylmethyl group, ethoxycarbonylmethyl group, propoxycarbonylmethyl group, isopropoxycarbonylmethyl group, butoxycarbonylmethyl group, isobutoxycarbonylmethyl group, t-butoxy Carbonylmethyl group, amyloxycarbonylmethyl group, isoamyloxycarbonylmethyl group, t-amyloxycarbonylmethyl group, 1-methoxycarbonylethyl group, 1-ethoxycarbonylethyl group, 1-propoxycarbonylethyl group, 1-isopropoxycarbonyl Ethyl group, 1-butoxycarbonylethyl group, 1-isobutoxycarbonylethyl group, 1-t-butoxycarbonylethyl group, 1-amyloxycarbonylethyl group, 1-isoa Oxy carbonyl ethyl group, etc. 1-t-butoxycarbonyl ethyl group, and
Examples of {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group include methoxyethoxycarbonylmethyl group, 1-methoxymethoxycarbonylethyl group, and the like.
The (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl group includes a cyclobutyloxycarbonylmethyl group, a cyclopentyloxycarbonylmethyl group, a cyclohexyloxycarbonylmethyl group, a 1-cyclobutyloxycarbonylethyl group, and a 1-cyclopentyloxycarbonylethyl group. Group, 1-cyclohexyloxycarbonylethyl group and the like,
Examples of the hydroxy C1-C6 alkyl group include a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group, and the like.
Represented by R ⁶ ,
Examples of the C1-C6 alkyl group include a methyl group and an ethyl group.
Examples of the C1-C6 haloalkyl group include a bromomethyl group, a dibromomethyl group, a tribromomethyl group, a 1-bromoethyl group, a chloromethyl group, a dichloromethyl group, and a trichloromethyl group.
Examples of the hydroxy C1-C6 alkyl group include a hydroxymethyl group.
(C1-C6 alkoxy) Examples of the C1-C6 alkyl group include a methoxymethyl group, an ethoxymethyl group, a propoxymethyl group, an isopropoxymethyl group, and the like.
{(C1-C6 alkoxy) C1-C6 alkoxy} C1-C6 alkyl group includes a methoxymethoxymethyl group, a methoxyethoxymethyl group, an ethoxymethoxymethyl group, and the like.
Examples of the (C1-C6 alkyl) carbonyloxy C1-C6 alkyl group include an acetyloxymethyl group, an ethylcarbonyloxymethyl group, an isopropylcarbonyloxymethyl group, and the like.
Examples of the (C1-C6 haloalkyl) carbonyloxy C1-C6 alkyl group include a trifluoroacetyloxymethyl group, a chloroacetyloxymethyl group, a trichloroacetyloxymethyl group, and the like.
Examples of the (C1-C6 alkoxy) carbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group, an amyloxycarbonyl group, an isopropoxycarbonyl group, an isobutoxycarbonyl group, and an isoamyloxycarbonyl group. ,
Examples of the C1-C6 alkyl group represented by R ⁷ include a methyl group,
Represented by R ⁸ ,
Examples of the C1-C6 alkyl group include a methyl group and an ethyl group.
Examples of the C1-C6 haloalkyl group include a chloromethyl group and a bromomethyl group.
Examples of the hydroxy C1-C6 alkyl group include a hydroxymethyl group.
(C1-C4 alkoxy) C1-C4 alkyl group includes a methoxymethyl group, an ethoxymethyl group, an isopropoxymethyl group, a butoxymethyl group, an isobutoxymethyl group, and the like.
(C1-C3 alkoxy) (C1-C3 alkoxy) C1-C3 alkyl group includes methoxymethoxymethyl group, methoxyethoxymethyl group, ethoxymethoxymethyl group, etc.
(C1-C6 alkyl) carbonyloxy C1-C6 alkyl group includes acetyloxymethyl group, ethylcarbonyloxymethyl group, isopropylcarbonyloxymethyl group, and the like.
(C1-C6 haloalkyl) carbonyl C1-C6 alkyl group includes 2-chloroethylcarbonyloxymethyl group, and the like.
Examples of the carboxy C1-C6 alkyl group include a carboxymethyl group,
(C1-C8 alkoxy) carbonyl group includes methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, butoxycarbonyl group, amyloxycarbonyl group, isopropoxycarbonyl group, isobutoxycarbonyl group, isoamyloxycarbonyl group and the like.
(C1-C6 haloalkoxy) carbonyl group includes 2-chloroethoxycarbonyl group, 2-bromoethoxycarbonyl group, 3-chlorobutoxycarbonyl group, 1-chloro-2-propoxycarbonyl group, 1,3-dichloro-2- Propoxycarbonyl group, 2,2-dichloroethoxycarbonyl group, 2,2,2-trifluoroethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, 2,2,2-tribromoethoxycarbonyl group, etc. And
Examples of the (C3-C10 cycloalkoxy) carbonyl group include a cyclobutyloxycarbonyl group, a cyclopentyloxycarbonyl group, a cyclohexyloxycarbonyl group, and the like.
(C3-C8 alkenyloxy) carbonyl group includes allyloxycarbonyl group, 3-butenyloxycarbonyl group, 1-methyl-2-propenyloxycarbonyl group, and the like.
(C3-C8 alkynyloxy) carbonyl group includes propargyloxycarbonyl group, 3-butynyloxycarbonyl group, 1-methyl-2-propynyloxycarbonyl group and the like.
Examples of the (C1-C6 alkyl) aminocarbonyl group include a methylaminocarbonyl group, an ethylaminocarbonyl group, a propylaminocarbonyl group, and the like.
Examples of the di (C1-C6 alkyl) aminocarbonyl group include a dimethylaminocarbonyl group, a diethylaminocarbonyl group, a diisopropylaminocarbonyl group, and the like.
Examples of the (C1-C6 alkyl) aminocarbonyloxy C1-C6 alkyl group include a methylaminocarbonyloxymethyl group, an ethylaminocarbonyloxymethyl group, a propylaminocarbonyloxymethyl group, and the like.
Examples of the di (C1-C6 alkyl) aminocarbonyloxy C1-C6 alkyl group include a dimethylaminocarbonyloxymethyl group and a diethylaminocarbonyloxymethyl group.
Examples of the C1-C6 alkyl group represented by R ²² include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, amyl, isoamyl, and t-amyl groups. ,
Examples of the C1-C6 haloalkyl group include 2-chloroethyl group, 2-bromoethyl group, 2,2,2-trifluoroethyl group, and the like.
Examples of the C3-C8 cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and the like.
Examples of the C3-C6 alkenyl group include an allyl group, a 1-methyl-2-propenyl group, a 3-butenyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and a 2-methyl-3-butenyl group. And
Examples of the C3-C6 haloalkenyl group include 2-chloro-2-propenyl group and 3,3-dichloro-2-propenyl group.
Examples of C3-C6 alkynyl group include propargyl group, 1-methyl-2-propynyl group, 2-butynyl group,
Examples of the C3-C6 haloalkynyl group include 3-bromopropargyl group,
Examples of the cyano C1-C6 alkyl group include a cyanoethyl group,
(C1-C4 alkoxy) Examples of the C1-C4 alkyl group include a methoxymethyl group, a methoxyethyl group, an ethoxymethyl group, an ethoxyethyl group,
Examples of the (C1-C4 alkylthio) C1-C4 alkyl group include a methylthioethyl group.
Examples of the carboxy C1-C6 alkyl group include a carboxymethyl group, a 1-carboxyethyl group, a 2-carboxyethyl group, and the like.
(C1-C8 alkoxy) carbonyl C1-C6 alkyl group includes methoxycarbonylmethyl group, ethoxycarbonylmethyl group, propoxycarbonylmethyl group, isopropoxycarbonylmethyl group, butoxycarbonylmethyl group, isobutoxycarbonylmethyl group, t-butoxy Carbonylmethyl group, amyloxycarbonylmethyl group, isoamyloxycarbonylmethyl group, t-amyloxycarbonylmethyl group, 1-methoxycarbonylethyl group, 1-ethoxycarbonylethyl group, 1-propoxycarbonylethyl group, 1-isopropoxycarbonyl Ethyl group, 1-butoxycarbonylethyl group, 1-isobutoxycarbonylethyl group, 1-t-butoxycarbonylethyl group, 1-amyloxycarbonylethyl group, 1-isoa Oxy carbonyl ethyl group, 1-t-butoxycarbonyl ethyl group, 1-amyloxycarbonyl ethyl, 1-isoamyl butyloxycarbonylethyl group, such as 1-t-amyloxycarbonyl ethyl group and the like,
Examples of {(C1-C4 alkoxy) C1-C4 alkoxy} carbonyl C1-C6 alkyl group include methoxymethoxycarbonylmethyl group, methoxyethoxycarbonylmethyl group, 1-methoxyethoxycarbonylethyl group, and the like.
The (C3-C8 cycloalkoxy) carbonyl C1-C6 alkyl group includes a cyclobutyloxycarbonylmethyl group, a cyclopentyloxycarbonylmethyl group, a cyclohexyloxycarbonylmethyl group, a 1-cyclobutyloxycarbonylethyl group, and a 1-cyclopentyloxycarbonylethyl group. Group, 1-cyclohexyloxycarbonylethyl group and the like.
Examples of the C1-C6 alkyl group represented by R ²³ and R ²⁴ include a methyl group and the like.
Examples of the halogen atom include a chlorine atom and a bromine atom.
Examples of the C1-C6 alkyl group represented by R ²⁵ include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, amyl, isoamyl, and t-amyl groups. ,
Examples of the C1-C6 haloalkyl group include 2-chloroethyl group, 2-bromoethyl group, 2,2,2-trifluoroethyl group, and the like.
Examples of the C3-C8 cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and the like.
Examples of the C3-C6 alkenyl group include an allyl group, a 1-methyl-2-propenyl group, a 3-butenyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, and a 2-methyl-3-butenyl group. It is done.
Examples of the C1-C6 alkyl group represented by R ²⁶ and R ²⁷ include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
The salt of the present compound-2 includes lithium salt, sodium salt, potassium salt, magnesium salt, calcium salt, methylamine salt, dimethylamine salt, trimethylamine salt, ethylamine salt, diethylamine salt, triethylamine salt, diisopropylethylamine salt. , Tri-n-propylamine salt, tri-n-butylamine salt, pyridine salt, 4-dimethylaminopyridine salt, N, N-dimethylaniline salt, N, N-diethylaniline salt and the like.
The compound of the present invention includes several isomers derived from double bonds, optical isomers and diastereomers derived from asymmetric carbon, and the compound of the present invention includes these isomers and mixtures thereof. included.

[式中ＱおよびＲ³は前記と同じ意味を表す。]
で示されるヒドラゾン化合物と一般式 化１５
〔化１５〕
Ｒ²ＣＨ（ＣＯＯＨ）₂
[式中、Ｒ²は前記と同じ意味を表す。]
で示されるマロン酸誘導体とを、塩基の存在下に反応させることにより製造される。（以下、本発明工程１と称す）
本反応の反応条件としては次の本発明工程１−１または本発明工程１−２に示す条件があげられる。 Next, a method for producing the compound of the present invention will be described.
1) Production Method of the Present Compound-1 The present compound-1 has the general formula 14
[ Chemical Formula 14 ]

[Wherein Q and R ³ represent the same meaning as described above. ]
A hydrazone compound represented by the general formula
[ Chemical 15 ]
R ² CH (COOH) ₂
[Wherein R ² represents the same meaning as described above. ]
It is manufactured by making the malonic acid derivative shown by react in presence of a base. (Hereinafter referred to as the present invention step 1)
The reaction conditions for this reaction include the conditions shown in the following Invention Step 1-1 or Invention Step 1-2.

I) Invention process 1-1
A method of reacting a hydrazone compound represented by general formula 14 with a malonic acid derivative represented by general formula 15 in the presence of a secondary amine and at least one of pyridine and quinoline. Usually, the reaction is performed in pyridine and / or quinoline, and the reaction temperature is usually 40 to 140 ° C, preferably 60 to 100 ° C. The reaction time ranges from instantaneous to 24 hours.
The amount of the reagent used for the reaction is 1 to 10 mol of the malonic acid derivative represented by the formula 15 with respect to 1 mol of the hydrazone compound represented by the formula 14 and 0.1% of the secondary amine. -5 mol, preferably 0.8-2 mol, more preferably 1-2 mol.
Examples of secondary amines include cyclic amines such as piperidine, morpholine and pyrrolidine, and dialkylamines such as diethylamine and diisopropylamine. In this reaction, as a co-solvent, aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene, dichloromethane, chloroform, carbon tetrachloride, 1, 2 -Halogenated hydrocarbons such as dichloroethane, 1,1,1-trichloroethane, chlorobenzene, dichlorobenzene, benzotrifluoride, diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, methyl-t-butyl ether -Ethers such as tellurium, nitriles such as acetonitrile and isobutyronitrile, esters such as ethyl acetate and butyl acetate, alcohols such as methanol, ethanol, propanol, butanol and isopropanol, N, N Acid amides such as dimethylformamide, dimethyl sulfoxide, it is also possible to use sulfur compounds or a mixture of sulfolane.

II) Invention process 1-2
A method of reacting a hydrazone compound represented by general formula 14 with a malonic acid derivative represented by general formula 15 in the presence of a base such as an organic base such as a dialkylaniline derivative or a tertiary amine. The reaction is carried out in the absence of solvent or in a solvent, and the range of the reaction temperature is usually 20 to 200 ° C, preferably 40 to 150 ° C. The range of reaction time is usually from instant to 72 hours.
The amount of the reagent used for the reaction is usually 1 to 10 mol, preferably 1 with respect to 1 mol of the hydrazone compound represented by the general formula 14 with respect to 1 mol of the malonic acid derivative represented by the general formula 15 The amount of the base is usually 1 mol to a large excess, preferably 1 to 10 mol, per 1 mol of the malonic acid derivative represented by the general formula 15.
Examples of the base include dialkylaniline derivatives such as N, N-dimethylaniline and N, N-diethylaniline, triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyldimethylamine, phenethyldimethylamine, N -Methylmorpholine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2. 2] Organic bases such as tertiary amines such as octane can be mentioned, and trialkylamines such as triethylamine, diisopropylethylamine, tri-n-propylamine, and tri-n-butylamine are preferable.
Solvents include hydrocarbons such as hexane, heptane, ligroin, petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1 1,1-trichloroethane, chlorobenzene, dichlorobenzene, benzotrifluoride and other halogenated hydrocarbons, diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, methyl-t-butyl ether Ethers such as ter, nitrogen-containing aromatic compounds such as pyridine and quinoline, acid amides such as N, N-dimethylformamide, esters such as ethyl acetate and butyl acetate, acetone, methyl ethyl ketone, methyl isobutyl ketone, Ketones such as cyclohexanone Acetonitrile, nitriles such as isobutyronitrile, methanol -, ethanol - le, propanol - le, butanol - le, isopropanol - alcohol, such as Le - Le acids, such as water or a mixture thereof.
The reaction solution after completion of the reaction of the present invention steps 1-1 and 1-2 is
(I) The reaction solution is concentrated as it is.
(Ii) The reaction solution is poured into an aqueous solution of a mineral acid such as hydrochloric acid or dilute sulfuric acid, and this is extracted with an organic solvent under acidic conditions, and then the organic layer is dried and concentrated.
(Iii) The reaction solution is poured into an aqueous solution of a base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, and then the organic layer is removed under alkaline conditions. Then, an aqueous solution of a mineral acid such as hydrochloric acid or dilute sulfuric acid is added to the aqueous layer to make the solution acidic, and then the aqueous layer is extracted with an organic solvent, and the organic layer is dried and concentrated.
The present compound-1 can be obtained by performing post-treatment such as recrystallization and, if necessary, purification by recrystallization, column chromatography and the like.
In addition, Compound 1 of the present invention is converted to Compound-2 of the present invention by the method described below, and then dissolved in water, the aqueous solution is extracted with an organic solvent, and impurities insoluble in water are dissolved in the organic layer. The organic layer is removed, an aqueous solution of a mineral acid such as hydrochloric acid or dilute sulfuric acid is added to the aqueous layer to make the solution acidic, the aqueous layer is extracted with an organic solvent, and the organic layer is dried and concentrated. It is also possible to purify.

2) Production method of the present compound-2 The present compound-2 can be produced by reacting the present compound-1 with a base. Examples of the base used in this reaction include inorganic bases such as lithium hydroxide, sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, sodium carbonate, or potassium carbonate, methylamine, dimethylamine, trimethylamine, ethylamine, Alkylamines such as diethylamine, triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, pyridines, optionally substituted pyridines such as 4-dimethylaminopyridine, N, N-dimethylaniline, And organic bases such as dialkylanilines such as N, N-diethylaniline. As reaction conditions, for example,
(I) A method of adding the present compound-1 to an aqueous solution of an inorganic base, extracting the reaction solution with an organic solvent, removing the organic layer, and then concentrating the aqueous layer (in this case, the present compound- 1 equivalent of inorganic base is preferably used per 1 mol).
(Ii) A process for producing the present compound-1 by reacting it with an organic base in an organic solvent and then concentrating the reaction solution.
Etc. The present compound-2 obtained by these methods can be purified by recrystallization or the like if necessary.
The compound of the present invention is usually obtained as a mixture of diastereomers, and these diastereomers can be used as a starting material for the next reaction without any particular separation, and if necessary, more precise chromatography. It is also possible to subject each to the next reaction after performing a separation operation such as the above.

As the malonic acid derivative represented by the general formula 15 used in the above production method, a commercially available one can be used, or it can be produced according to a known method.
Further, the hydrazone compound represented by the general formula 14 is represented by the general formula 16
[ Chemical Formula 16 ]
CF ₃ C (═O) CV ₂ R ³
[Wherein R ³ represents the same meaning as described above, and V represents an iodine atom, a bromine atom, or a chlorine atom. ]
Is reacted with water in the presence of a base to give a general formula 17
[ Chemical Formula 17 ]
CF ₃ C (═O) C (═O) R ³
[Wherein R ³ represents the same meaning as described above]
To a carbonyl compound represented by the formula (1) or a hydrate thereof, or an acetal derivative (hereinafter referred to as Reaction 1),
[ Chemical formula 18 ]
Q-NHNH ₂
[Wherein Q represents the same meaning as described above. ]
It can manufacture by making the hydrazine derivative shown by react (it is hereafter described as reaction 2).
The above reaction 1 is usually carried out in a solvent, the reaction temperature range is usually 0 to 100 ° C., the reaction time range is usually from the instant to 72 hours, and the amount of the reagent used for the reaction is represented by the general formula The amount of water and the base is 1 mol per mol of the compound represented by Chemical formula 16, but the theoretical amount is 2 mol, but an excess can be used if necessary.
As the base, both organic bases and inorganic bases can be used, and examples thereof include sodium acetate and potassium acetate.
The carbonyl compound represented by the general formula 17 can also be reacted as a hydrate or an acetal derivative in the presence of water or alcohol.

The reaction 2 is usually carried out in a solvent, the reaction temperature range is usually 0 to 100 ° C., and the reaction time range is usually instantaneous to 72 hours. The amount of the reagent used in the reaction is 1 mol of the hydrazine derivative represented by the general formula 18 with respect to 1 mol of the compound represented by the general formula 16 used in the reaction 1, If necessary, an excess amount of the compound represented by the general formula 16 can be used. The hydrazine derivative can also be used as a salt such as its hydrochloride or sulfate.
Examples of the solvent used in Reaction 1 and Reaction 2 include aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, dichlorobenzene, Halogenated hydrocarbons such as benzotrifluoride, ethers such as diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, methyl t-butyl ether, methanol Alcohols, ethanol, ethylene glycol, isopropanol and the like, water or a mixture thereof.
After completion of the reaction, water is added as necessary, and the resulting crystals are collected by filtration, or subjected to usual post-treatment such as organic solvent extraction and concentration. The target product can be isolated by further purification by an operation such as crystallization.
The hydrazine derivative represented by the general formula is represented by the general formula
[ Chemical formula 19 ]
Q-NH ₂
[Wherein Q represents the same meaning as described above. ]
Can be produced by diazotization with nitrous acid, sodium nitrite or the like under acidic conditions and then reduction with stannous chloride or the like. (For example, see Organic Synthetic Reactive Volume 1, p442)
The aniline derivative represented by the general formula 19 is, for example, European Patent Application Publication No. EP-61741-A, US Patent Specification USP 4,670,046, USP 4,770,695, USP 4,709,049, USP4. 640,707, USP 4,720,297, USP 5,169,431, Japanese Patent Application Laid-Open No. 63-156787, or can be produced according to the method described therein.

[式中、Ｑは前記と同じ意味を表し、Ｒ²⁸はＣ１−Ｃ６アルキル基を表す。]
各工程の反応は例えば下記の通りである。
（１）化合物［Ｉ］から化合物［ＩＩ］を製造する工程
化合物［ＩＩ］は、化合物［Ｉ］を酸性条件下、水中で亜硝酸ナトリウム、亜硝酸カリウム等の亜硝酸塩と反応させて、対応するジアゾニウム塩とした後、該ジアゾニウム塩と一般式 化２１
〔化２１〕
ＣＦ₃Ｃ（＝Ｏ）ＣＨ₂Ｃ（＝Ｏ）ＯＲ²⁸
[式中、ＱおよびＲ²⁸は前記と同じ意味を表す。]
で示される化合物とを、酢酸ナトリウム、ピリジン等の塩基の存在下で反応させることにより製造することができる(Tetrahedron,Vol.35,p2013(1979)参照）
（２）化合物〔ＩＩ〕から化合物〔ＩＩＩ〕を製造する工程
化合物〔ＩＩＩ〕は化合物〔ＩＩ〕を通常、溶媒中塩基の存在下で加水分解することにより製造することができる。
反応温度の範囲は通常０〜１００℃であり、反応時間の範囲は通常瞬時〜２４時間である。反応に供される試剤の量は、化合物〔ＩＩ〕１モルに対して、塩基の量は１モルの割合が理論量であるが、必要に応じて変化させる事ができる。塩基としては、水酸化ナトリウム、水酸化リチウム、水酸化リチウム１水和物、水酸化バリウム、水酸化カリウム等の無機塩基があげられる。
用いられる溶媒としては、ヘキサン、ヘプタン、リグロイン、石油エ−テル等の脂肪族炭化水素類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン、ジクロロベンゼン、ベンゾトリフルオリド等のハロゲン化炭化水素類、ジエチルエ−テル、ジイソプロピルエ−テル、１，４−ジオキサン、テトラヒドロフラン、エチレングリコ−ルジメチルエ−テル、メチル−ｔ−ブチルエ−テル等のエ−テル類、メタノ−ル、エタノ−ル、エチレングリコ−ル、イソプロパノ−ルなどのアルコ−ル類、水等あるいはそれらの混合物があげられる。
（３）化合物〔ＩＩＩ〕から化合物〔ＩＶ〕を製造する工程
化合物〔ＩＶ〕は化合物〔ＩＩＩ〕を溶媒中で加熱し、脱炭酸することにより製造することができる。
該反応の温度範囲は、通常５０〜２００℃であり、反応時間の範囲は、通常瞬時〜７２時間である。反応に用いられる溶媒としては、ヘキサン、ヘプタン、リグロイン、石油エ−テル等の脂肪族炭化水素類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、クロロホルム、四塩化炭素、１，２−ジクロロエタン、クロロベンゼン、ジクロロベンゼン、ベンゾトリフルオリド等のハロゲン化炭化水素類、ジエチルエ−テル、ジイソプロピルエ−テル、１，４−ジオキサン、テトラヒドロフラン、エチレングリコ−ルジメチルエ−テル、メチル−ｔ−ブチルエ−テル等のエ−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等の酸アミド類、トリエチルアミン、ジイソプロピルエチルアミン、Ｎ，Ｎ−ジメチルアニリン、Ｎ，Ｎ−ジエチルアニリン、Ｎ−メチルモルホリン等の第三級アミン類、ピリジン、ピコリン等の含窒素芳香族化合物、ジメチルスルホキシド、スルホラン等の硫黄化合物、ギ酸、酢酸、プロピオン酸等の脂肪酸類、メタノ−ル、エタノ−ル、エチレングリコ−ル、イソプロパノ−ルなどのアルコ−ル類、水等あるいはそれらの混合物などが挙げられる。
本反応は、必要に応じて銅等の金属を触媒として用いることもできる。
反応終了後の反応液は、生じた結晶を濾集するか、又は有機溶媒抽出および濃縮等の通常の後処理を行い、必要ならばクロマトグラフィ−、再結晶等の操作によって更に精製することにより、目的物を単離することができる。
なお、化合物〔ＩＶ〕において、ＱがＱ−１を表わし、そのＢがＯＲ¹またはＳＲ¹であり、Ｒ¹がカルボキシＣ１−Ｃ６アルキル基を表すヒドラゾン化合物は、化合物〔ＩＩ〕において、ＢがＯＲ¹またはＳＲ¹であり、Ｒ¹が（Ｃ１−Ｃ８アルコキシ）カルボニルＣ１−Ｃ６アルキル基を表す化合物を経由し、これを、加水分解および脱炭酸することにより製造することもできる。 In the hydrazone compound represented by the general formula 14, the compound in which R ³ is a hydrogen atom can also be produced from the aniline derivative represented by the general formula 19 according to the following scheme 20.
[ Chemical formula 20 ]

[Wherein, Q represents the same meaning as described above, and R ²⁸ represents a C1-C6 alkyl group. ]
The reaction in each step is as follows, for example.
(1) Step of producing compound [II] from compound [I] Compound [II] is prepared by reacting compound [I] with nitrites such as sodium nitrite and potassium nitrite in water under acidic conditions. After forming a diazonium salt, the diazonium salt and the general formula
[ Chemical Formula 21 ]
CF ₃ C (═O) CH ₂ C (═O) OR ²⁸
[Wherein Q and R ²⁸ represent the same meaning as described above. ]
In the presence of a base such as sodium acetate or pyridine (see Tetrahedron, Vol. 35, p2013 (1979)).
(2) Step of producing compound [III] from compound [II] Compound [III] can be produced by hydrolyzing compound [II] usually in the presence of a base in a solvent.
The reaction temperature range is usually 0 to 100 ° C., and the reaction time range is usually instantaneous to 24 hours. The amount of the reagent to be used for the reaction is 1 mol of the compound [II], and the amount of the base is 1 mol, but it can be changed as necessary. Examples of the base include inorganic bases such as sodium hydroxide, lithium hydroxide, lithium hydroxide monohydrate, barium hydroxide, and potassium hydroxide.
Solvents used include aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene, and halogenated carbonization such as chlorobenzene, dichlorobenzene and benzotrifluoride. Hydrogens, diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, ethers such as methyl-t-butyl ether, methanol, ethanol, ethylene Examples thereof include alcohols such as glycol and isopropanol, water and the like, or a mixture thereof.
(3) Step of producing compound [IV] from compound [III] Compound [IV] can be produced by heating compound [III] in a solvent and decarboxylation.
The temperature range of the reaction is usually 50 to 200 ° C., and the reaction time is usually instant to 72 hours. Solvents used for the reaction include aliphatic hydrocarbons such as hexane, heptane, ligroin, petroleum ether, aromatic hydrocarbons such as benzene, toluene, xylene, chloroform, carbon tetrachloride, 1,2-dichloroethane. Halogenated hydrocarbons such as chlorobenzene, dichlorobenzene and benzotrifluoride, diethyl ether, diisopropyl ether, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, methyl t-butyl ether, etc. Ethers, acetone, methyl ethyl ketone, methyl isobutyl ketone, ketones such as cyclohexanone, acid amides such as N, N-dimethylformamide, triethylamine, diisopropylethylamine, N, N-dimethylaniline, N, N-diethylaniline, N- Tertiary amines such as tilmorpholine, nitrogen-containing aromatic compounds such as pyridine and picoline, sulfur compounds such as dimethyl sulfoxide and sulfolane, fatty acids such as formic acid, acetic acid and propionic acid, methanol, ethanol and ethylene Examples include alcohols such as glycol and isopropanol, water and the like, and mixtures thereof.
This reaction can also use metals, such as copper, as a catalyst as needed.
The reaction solution after completion of the reaction is collected by filtering the produced crystals or subjected to usual post-treatment such as organic solvent extraction and concentration, and if necessary, further purification by operations such as chromatography, recrystallization, The target product can be isolated.
In the compound [IV], Q represents Q-1, B is OR ¹ or SR ¹ , and R ¹ represents a carboxy C1-C6 alkyl group. It can also be produced by hydrolysis and decarboxylation via a compound which is OR ¹ or SR ¹ and R ¹ represents a (C1-C8 alkoxy) carbonyl C1-C6 alkyl group.

で示される化合物。
Next, the compounds of the present invention obtained by this production method are shown in (Table 1) to (Table 22), and in the reaction step 1 of the present invention, and the hydrazone compound represented by the general formula 14 and the general formula 15 The malonic acid derivatives shown are exemplified in (Table 23) and (Table 24), respectively, but the present invention is not limited thereto. In each table, c represents cyclo, i represents iso, Et represents an ethyl group, and Bu represents a butyl group.
General formula
[ Chemical Formula 22 ]

A compound represented by

で示される化合物
General formula
[ Chemical Formula 23 ]

Compound represented by

A hydrazone compound represented by the general formula:

Malonic acid derivative represented by the general formula

Next, a process for producing a pyridazin-3-one derivative represented by the general formula 10 from the present compound-1 (hereinafter referred to as the present invention process 2) will be described.
The present invention step 2 can be carried out under various reaction conditions. Among them, typical methods include the following seven methods (invention steps 2-1, 2-2, 2-3, 2-4, 2-5, 2-6, 2-7).
In addition, although this invention compound-1 is generally used as a raw material compound used by this invention process 2, this invention compound is used depending on reaction conditions (For example, when using the conditions of this invention process 2-3, 2-4). -2 can also be used to produce the compound-1 of the present invention in the reaction system.

1) Invention process 2-1
This invention compound-1 can manufacture the pyridazin-3-one derivative shown by General formula 10 by making this react at the reaction temperature of 80-250 degreeC.
The reaction is carried out without solvent or in a solvent, and the reaction temperature range is usually from 80 to 250 ° C, preferably from 120 to 160 ° C. The reaction time range is from instant to 72 hours.
Solvents used in the reaction include aliphatic hydrocarbons such as heptane, octane and ligroin, aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene and mesitylene, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, Halogenated hydrocarbons such as chlorobenzene and benzotrifluoride, ethers such as 1,4-dioxane, ethylene glycol dimethyl ether and methyl-t-butyl ether, ketones such as methyl isobutyl ketone and cyclohexanone, Examples thereof include acid amides such as N, N-dimethylformamide, alcohols such as propanol, butanol, amyl alcohol, ethylene glycol and diethylene glycol, or mixtures thereof. The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water and extracting it with an organic solvent, drying and concentrating the organic layer, A pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by recrystallization, column chromatography or the like if necessary.

2) Invention process 2-2
This invention compound-1 can manufacture the pyridazin-3-one derivative shown by General formula 10 by making a base act on this.
Examples of the base used in the reaction include pyridine, quinoline, isoquinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, Nitrogen-containing aromatic compounds such as 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 3-chloropyridine, 2-ethyl-3-methylpyridine, 5-ethyl-2-methylpyridine, N, Dialkylaniline derivatives such as N-dimethylaniline and N, N-diethylaniline, triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyldimethylamine, phenethyldimethylamine, N-methylmorpholine, 1, 8-Diazabicyclo [5.4.0] undec-7-ene, 1,5-dia Bicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] tertiary amines such as octane, and the like. Preferred bases include trialkylamines such as triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine or pyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2 Alkyl groups such as 1,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 2-ethyl-3-methylpyridine, 5-ethyl-2-methylpyridine, etc. And pyridines optionally substituted with.
The amount of the base to be used is a catalytic amount to a large excess amount, preferably a catalytic amount to 10 mol with respect to 1 mol of the present compound-1. Although the range of reaction temperature changes with bases to be used, it is 80-250 degreeC normally, Preferably it is 120-160 degreeC. The reaction time range is from instant to 72 hours.
The reaction is usually carried out in a solvent or in the absence of a solvent. Solvents used for the reaction include aliphatic hydrocarbons such as hexane, heptane, octane and ligroin, and aromatics such as benzene, toluene, ethylbenzene, xylene and mesitylene. Hydrocarbons, halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, trichlorobenzene, and benzotrifluoride, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl-t-butyl ether , Ketones such as methyl isobutyl ketone and cyclohexanone, acid amides such as N, N-dimethylformamide, ethanol, propanol, butanol, amyl alcohol, ethylene glycol, diethylene glycol, etc. Alcohols or mixtures thereof And the like. The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water, extracting with an organic solvent, drying and concentrating the organic layer, if necessary. For example, the pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by operations such as recrystallization and column chromatography.
In this reaction step, the reaction can be carried out while removing water from the reaction system, for example, using a desiccant such as molecular sieve.

3) Invention process 2-3
The compound of the present invention can produce a pyridazin-3-one derivative represented by the general formula 10 by allowing an acid to act on the compound.
Examples of acids used in the reaction include acetic acid, propionic acid, trimethylacetic acid, chloroacetic acid, trifluoroacetic acid, phenylacetic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and other fatty acids, benzoic acid, and 4-nitrobenzoic acid. Benzoic acids such as 4-chlorobenzoic acid, 3,5-dinitrobenzoic acid, 4-methoxybenzoic acid, sulfonic acids such as p-toluenesulfonic acid, benzenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, etc. Examples thereof include organic acids, inorganic acids such as sulfuric acid, hydrochloric acid and phosphoric acid, and acidic cation exchange resins such as Amberlite CG-50 and Amberlite IR-120. The amount of the acid used is a catalytic amount to a large excess amount, and preferably a catalytic amount to 10 mol with respect to 1 mol of the compound of the present invention. Although the range of reaction temperature changes with acids to be used, it is usually 50-250 degreeC. The reaction time range is from instant to 72 hours.
The reaction is carried out without solvent or in a solvent. Examples of the solvent used for the reaction include aliphatic hydrocarbons such as hexane, heptane, octane and ligroin, and aromatic carbonization such as benzene, toluene, ethylbenzene, xylene and mesitylene. Hydrogen, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene, benzotrifluoride and other halogenated hydrocarbons, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether , Ethers such as methyl-t-butyl ether, ketones such as methyl isobutyl ketone and cyclohexanone, or mixtures thereof.
The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water, extracting with an organic solvent, drying and concentrating the organic layer, if necessary. For example, the pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by operations such as recrystallization and column chromatography. When an acidic cation exchange resin is used, the post-treatment operation is performed after removing the ion exchange resin by filtration.

4) Invention process 2-4
The compound of the present invention can produce a pyridazin-3-one derivative represented by the general formula 10 by allowing an acid and a base to act on the compound.
Acids used for the reaction include acetic acid, propionic acid, trimethylacetic acid, trichloroacetic acid, trifluoroacetic acid, phenylacetic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid and other fatty acids, benzoic acid, 4-nitrobenzoic acid Benzoic acids such as 4-chlorobenzoic acid, 3,5-dinitrobenzoic acid, 4-methoxybenzoic acid, sulfonic acids such as p-toluenesulfonic acid, methanesulfonic acid, trifluoromethanesulfonic acid, sulfuric acid, hydrochloric acid, phosphoric acid Examples of the base used in the reaction include pyridine, quinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 3-chloropyridine, 2-ethyl-3- Nitrogen-containing aromatic compounds such as tilpyridine and 5-ethyl-2-methylpyridine, dialkylaniline derivatives such as N, N-dimethylaniline and N, N-diethylaniline, and secondary amines such as piperidine, pyrrolidine, morpholine and diethylamine , Triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyldimethylamine, phenethyldimethylamine, N-methylmorpholine, 1,8-diazabicyclo [5.4.0] undec-7-ene , Tertiary amines such as 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] octane, lithium hydroxide, sodium hydroxide, hydroxide Examples thereof include inorganic bases such as potassium, ammonia and the like. In this reaction step, the reaction can be carried out with any combination of these acids and bases, but preferred acid and base combinations include acetic acid, propionic acid, trimethylacetic acid, chloroacetic acid, trifluoroacetic acid, and phenylacetic acid. Fatty acids or benzoic acid, 4-nitrobenzoic acid, 4-chlorobenzoic acid, 3,5-dinitrobenzoic acid or benzoic acid such as 4-methoxybenzoic acid and pyridine, quinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3,5-lutidine, 3-chloropyridine, 2 -Nitrogen-containing aromatic compounds such as ethyl-3-methylpyridine or 5-ethyl-2-methylpyridine or triethyla , Diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyldimethylamine, phenethyldimethylamine, N-methylmorpholine, 1,8-diazabicyclo [5.4.0] undec-7-ene, , 5-diazabicyclo [4.3.0] non-5-ene or a combination of tertiary amines such as 1,4-diazabicyclo [2.2.2] octane. The amount of the acid used is a catalytic amount to a large excess amount with respect to 1 mol of the compound of the present invention. The amount of the base used is a catalytic amount to a large excess with respect to 1 mol of the compound of the present invention. Moreover, this reaction can also be performed using the salt obtained from an acid and a base. Specific examples of the salt include salts obtained from the above-mentioned preferred acids and preferred bases, sodium salts, potassium salts, ammonium salts of fatty acids such as acetic acid, propionic acid, pivalic acid, trifluoroacetic acid, and phenylacetic acid. Salts, sodium salts of benzoic acids such as 4-nitrobenzoic acid, 4-chlorobenzoic acid, 3,5-dinitrobenzoic acid, 4-methoxybenzoic acid, potassium salts, ammonium salts, pyridine, quinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2,6-lutidine, 3,4-lutidine, 3, Nitrogen-containing aromatic compounds such as 5-lutidine, 3-chloropyridine, 2-ethyl-3-methylpyridine, 5-ethyl-2-methylpyridine, and triethylamine Examples include tertiary amine hydrochlorides, sulfates, ammonium chlorides, ammonium sulfates, etc., such as N, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyldimethylamine, phenethyldimethylamine, N-methylmorpholine. It is done.
The reaction time range is instantaneous to 72 hours, and the reaction temperature range may vary depending on the acid and base used, but is usually 80 to 250 ° C.
The reaction is carried out without solvent or in a solvent. Examples of the solvent used for the reaction include aliphatic hydrocarbons such as hexane, heptane, octane and ligroin, and aromatic carbonization such as benzene, toluene, ethylbenzene, xylene and mesitylene. Hydrogens, halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, trichlorobenzene, and benzotrifluoride, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl-t-butyl ether , Acid amides such as N, N-dimethylformamide, ethanol, propanol, butanol, amyl alcohol, ethylene glycol, alcohols such as diethylene glycol, or mixtures thereof. It is done. Also, ketones such as methyl isobutyl ketone and cyclohexanone can be used as a solvent. However, when a secondary amine is used as a base, it is not preferable to use such ketones as a solvent.
The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water, extracting with an organic solvent, drying and concentrating the organic layer, if necessary. For example, the pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by operations such as recrystallization and column chromatography.
In this reaction, it is possible to carry out the reaction while removing water from the reaction system, such as using a desiccant such as molecular sieve.

5) Invention process 2-5
The present compound-1 can be produced by reacting this with a haloformate in the presence of a base to produce a pyridazin-3-one derivative represented by general formula 10.
Examples of the haloformate used in the reaction include methyl chloroformate, ethyl chloroformate, propyl chloroformate, and methyl bromate.
Examples of the base used in the reaction include pyridine, quinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2, Nitrogen-containing aromatic compounds such as 6-lutidine, 3,4-lutidine, 3,5-lutidine, 3-chloropyridine, 2-ethyl-3-methylpyridine, 5-ethyl-2-methylpyridine, N, N- Dialkylaniline derivatives such as dimethylaniline and N, N-diethylaniline, triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyl-dimethylamine, phenethyldimethylamine, N-methylmorpholine, 1,8 -Diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [ .3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] tertiary amines such as octane, organic bases and the like.
The amount of the reagent used in the reaction is 1 to 10 moles of the haloformate and 1 to 20 moles of the base with respect to 1 mole of the present compound-1. The reaction time range is from instant to 72 hours. The range of the reaction temperature is usually -20 to 100 ° C.
The reaction is carried out without solvent or in a solvent. Examples of the solvent used for the reaction include aliphatic hydrocarbons such as hexane, heptane, octane and ligroin, and aromatic carbonization such as benzene, toluene, ethylbenzene, xylene and mesitylene. Hydrogen, dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene, benzotrifluoride and other halogenated hydrocarbons, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether , Ethers such as methyl-t-butyl ether, or mixtures thereof.
The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water, extracting with an organic solvent, drying and concentrating the organic layer, if necessary. For example, the pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by operations such as recrystallization and column chromatography.

6) Invention process 2-6
The present compound-1 can be produced by reacting this with a condensing agent in the presence of a base to produce a pyridazin-3-one derivative represented by the general formula 10.
Examples of the condensing agent used in the reaction include 1,3-dicyclohexylcarbodiimide, 1-ethyl-3- (3′-dimethylaminopropyl) carbodiimide, diethyl phosphate cyanide, acetic anhydride, acetyl chloride and the like.
Examples of the base used in the reaction include organic bases such as nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine, and tertiary amines such as triethylamine, diisopropylethylamine and tri-n-butylamine. The amount of the reagent used in the reaction is 1 to 10 mol of the condensing agent and 1 to 20 mol of the base with respect to 1 mol of the present compound-1.
The reaction time range is instantaneous to 72 hours, and the reaction temperature range is usually -20 to 150 ° C.
The reaction is carried out without solvent or in a solvent, and examples of the solvent used for the reaction include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin, and aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene. , Dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene, benzotrifluoride and other halogenated hydrocarbons, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, methyl Examples include ethers such as -t-butyl ether or mixtures thereof.
The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water, extracting with an organic solvent, drying and concentrating the organic layer, if necessary. For example, the pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by operations such as recrystallization and column chromatography.

7) Invention process 2-7
The present compound-1 can be produced by reacting this with a halogenating agent in the presence of a base to produce a pyridazin-3-one derivative represented by general formula 10.
Examples of the halogenating agent used in the reaction include thionyl chloride, phosgene, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride and the like.
Examples of the base used in the reaction include pyridine, quinoline, 4-dimethylaminopyridine, 2-picoline, 3-picoline, 4-picoline, 2,3-lutidine, 2,4-lutidine, 2,5-lutidine, 2, Nitrogen-containing aromatic compounds such as 6-lutidine, 3,4-lutidine, 3,5-lutidine, 3-chloropyridine, 2-ethyl-3-methylpyridine, 5-ethyl-2-methylpyridine, N, N- Dialkylaniline derivatives such as dimethylaniline and N, N-diethylaniline, triethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, benzyl-dimethylamine, phenethyldimethylamine, N-methylmorpholine, 1,8 -Diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [ .3.0] non-5-ene, 1,4-diazabicyclo [2.2.2] tertiary amines such as octane, organic bases and the like.
The amount of the reagent used in the reaction is 1 to 10 mol of the halogenating agent and 1 to 20 mol of the base with respect to 1 mol of the compound-1 of the present invention.
The reaction time range is instantaneous to 72 hours, and the reaction temperature range is usually -20 to 150 ° C.
The reaction is carried out without solvent or in a solvent, and examples of the solvent used for the reaction include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin, and aromatic hydrocarbons such as benzene, toluene, xylene, and mesitylene. , Dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, dichlorobenzene, trichlorobenzene, benzotrifluoride and other halogenated hydrocarbons, 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, methyl Examples include ethers such as -t-butyl ether or mixtures thereof.
Furthermore, this reaction can also be performed by adding a catalytic amount of N, N-dimethylformamide.
The reaction solution after completion of the reaction is subjected to a concentration operation as it is, or a post-treatment operation such as pouring the reaction solution into water, extracting with an organic solvent, drying and concentrating the organic layer, if necessary. For example, the pyridazin-3-one derivative represented by the general formula 10 can be obtained by purification by operations such as recrystallization and column chromatography.

In addition, when performing this invention process 2-2 and this invention process 2-4, after performing this reaction process 1, this invention process 2 can also be performed as it is, without isolating this invention compound-1. it can.
In this case, the hydrazone compound represented by the general formula 14 is reacted with the malonic acid derivative represented by the general formula 15 by the method described in the step 1-1 or 1-2 of the present invention to cause the present compound-1 to react. After generating
1) Continue reaction under the conditions described in the present invention step 2-2,
2) The acid illustrated in this invention process 2-4 is added to a reaction liquid, and it reacts on the conditions as described in this invention process 2-4, The pyridazin-3-one derivative shown by General formula 10 is obtained. Obtainable.
In the step 2 of the present invention, depending on the conditions, a pyridazine-3-one ring may be formed and a pyridazine-3-one derivative in which a substituent of the benzene ring is converted may be obtained. Eg, Q is, in the general formula of 11, a Q-1, B is OR ^1, using the present invention compounds in which R ¹ is C1-C6 alkyl group, when the present invention step 2-3, In general formula 10, a pyridazin-3-one derivative in which Q is Q-1 and B is OH may be obtained.

で示される化合物。
Some of the compounds that can be produced by the present invention step 2 are shown in (Table 25).
General formula
[ Chemical formula 24 ]

A compound represented by

The pyridazin-3-one derivative represented by the general formula 10 has an excellent herbicidal effect, and has a herbicidal effect on various weeds which are problematic in the foliage treatment and soil treatment of the field.
Polygonum convolvulus, Polygonum lapathiolium, Polygonum pensylvanicum, Polygonum persicaria, Rumex crispus, Rumex obtus
Physalis Weed Physalis (Portulaca oleracea)
Weeping weed (Stellaria media)
Rubiaceae weeds Chenopodium album, Kochia scoparia
Amaranthus retroflexus, Amaranthus hybridus
Brassicaceae weed Wild radish (Raphanus raphanistrum), Noharagarashi (Sinapis arvensis), Nazuna (Capsella bursa-pastoris)
Leguminosae weeds Sesbania exaltata, Cassia obtusifolia, Florida vegaweed (Desmodium tortuosum), White clover (Trifolium repens)
Mallow Weed Ibibi (Abutilon theophrasti), American King Deer (Sida spinosa)
Violet weed Field pangee (Viola arvensis), Wild pangee (Viola tricolor)
Rubiaceae weed (Galium aparine)
Convolvulus arvensis, Convolvulus arvensis
Lamiaceae weeds (Lamium purpureum), photokenosa (Lamium amplexicaule)
Solanum nigrum (Datura stramonium) and Solanum nigrum
Weeping weeds Veronica persica, Veronica hederaefolia
Asteraceae weeds (Xanthium pensylvanicum), wild sunflower (Helianthus annuus), dog chamomile (Matricaria perforata or inodora), corn marigold (Chrysanthemum segetum), oricia (Matricaria matricarioides), ragweed (Ambrosia) Ambrosia trifida), Erigeron canadensis, Artemisia princeps, Solidago altissima
Purple Weed Forget-me-not (Myosotis arvensis)
Asperpias syriaca
Euphorbiaceae Weeping Euphorbia helioscopia, Euphorbia maculata
Gramineae weeds (Echinochloa crus-galli), Enochorogusa (Setaria viridis), Akinoenokorogusa (Setaria faberi), Bark beetle (Digitaria sanguinalis), Bark beetle (Eleusine indica), Pomegranate (Poa annuacur), Black grass (Poa annuacur) Avena fatua, Sorghum halepense, Agropyron repens, Bromus tectorum, Cynodon dactylon, Paccum dichotomiflorum, Texas pumcum-Phumcum texanum vulgare)
Commelina communis
Horsetail weeds horsetail (Equisetum arvense)
Cyperus weeds
Moreover, the pyridazin-3-one derivative represented by the general formula 10 can effectively weed various weeds which are problematic in no-tillage cultivation such as soybean, corn, wheat and the like.

In addition, the pyridazin-3-one derivative represented by the general formula 10 has herbicidal activity against various weeds that cause problems in the flooding treatment of paddy fields. Gramineae weeds, Echinochloa oryzicola
Lornia weeds Azena (Lindernia procumbens)
Misohidae weeds Rotala indica, Ammannia multiflora
Erosine triandra weed
Cyperus weed
Weeping moss weed (Monochoria vaginalis)
Omodaka Weed Urikawa (Sagittaria pygmaea), Omodaka (Sagittaria trifolia), Heramodaka (Alisma canaliculatum)
Hiramushi Weed Hiramushiro (Potamogeton distinctus)
Seriaceae weed Seri (Oenanthe javanica)
Furthermore, the pyridazin-3-one derivative represented by the general formula 10 can weed a wide range of weeds that occur in orchards, pastures, lawns, forestry or waterways, canals or other non-agricultural lands.
The pyridazin-3-one derivative represented by the general formula 10 has herbicidal effects on aquatic weeds such as water hyacinth (Eichhornia crassipes) that occur in waterways, canals and the like.
Further, pyridazin-3-one derivatives represented by the general formula 10 include corn (Zea mays), wheat (Triticum aestivum), barley (Hordeum vulgare), rice (Oryza sativa), sorghum (Sorghum bicolor), soybean (Glycine). max), cotton (Gossypium spp.), sugar beet (Beta vulgaris), peanut (Arachis hypogaea), sunflower (Helianthus annuus), rapeseed (Brassica napus), etc. Can exhibit selectivity between crops and weeds.

When the pyridazin-3-one derivative represented by the general formula 10 is used as an active ingredient of a herbicide, it is usually mixed with a solid carrier, a liquid carrier, a surfactant or other formulation adjuvant, It is used by formulating it as an agent, suspension, granule, concentrated emulsion, granule wettable powder and the like.
These preparations contain 0.001 to 80%, preferably 0.005 to 70%, by weight of the pyridazin-3-one derivative represented by the general formula 10 as an active ingredient.
Solid carriers include kaolin clay, attapulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomite, calcite and other mineral fine powders, walnut shell powder and other organic fine powders, urea and other water soluble organic fine powders Inorganic salt fine powders such as ammonium sulfate and fine powders of synthetic silicon hydroxide, and the like. Liquid carriers include aromatic hydrocarbons such as methylbenzene, methylnaphthalene, phenylxylylethane, and xylene, isopropanol, Alcohols such as ethylene glycol and 2-ethoxyethanol, esters such as dialkyl phthalate, ketones such as acetone, cyclohexanone and isophorone, mineral oils such as machine oil, soybean oil, cottonseed oil, etc. Vegetable oil, dimethyl sulfoxide, N, N-dimethylformamide, acetonitrile N- methylpyrrolidone, water and the like.
Surfactants used for emulsification, dispersion, wet spreading, etc. include alkyl sulfate esters, alkyl sulfonates, alkyl aryl sulfonates, dialkyl sulfosuccinates, polyoxyethylene alkyl aryl ether phosphates Anionic surfactants such as ester salts, polyoxyethylene alkyl ethers, polyoxyethylene alkyl aryl ethers, polyoxyethylene polyoxypropylene block copolymers, sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters, etc. Nonionic surfactants and the like can be mentioned.
Examples of other adjuvants for preparation include lignin sulfonate, alginate, polyvinyl alcohol, gum arabic, CMC (carboxymethylcellulose), PAP (isopropyl acid phosphate) and the like.

The pyridazin-3-one derivative represented by the general formula 10 is usually formulated and treated with soil, foliage or watering before or after emergence of weeds. Examples of the soil treatment include soil surface treatment, soil admixing treatment, etc., and the foliage treatment includes treatment from above the plant body and local treatment for treating only weeds so as not to adhere to crops.
When a pyridazin-3-one derivative represented by the general formula 10 is used as an active ingredient of a herbicide, the treatment amount depends on weather conditions, formulation form, treatment time, treatment method, soil condition, target crop, target weed, etc. However, it is usually 0.01 to 10000 g, preferably 1 to 8000 g per hectare. Emulsions, wettable powders, suspensions, concentrated emulsions, wettable powders, etc. Dilute with 10 liters to 1000 liters of hectare (with an adjunct such as a spreader added if necessary) and treat the granules and certain suspensions normally without any dilution. To process. Here, as the auxiliary agent used as necessary, in addition to the above-mentioned surfactant, polyoxyethylene resin acid (ester), lignin sulfonate, abietic acid salt, dinaphthylmethane disulfonate, crop oil concentrate (Crop oil concentrate), vegetable oils such as soybean oil, corn oil, cottonseed oil, sunflower oil and the like.

EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated in more detail, this invention is not limited to these.
1) Production Example of the Compound of the Present Invention (Process 1 of the Present Invention)
Production Example 1-1
Under a nitrogen stream, 3.086 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) (Compound 3-1) was dissolved in 20 ml of pyridine. . Piperidine (1.07 ml) and methylmalonic acid (2.561 g) were added to the solution, heated to 80 ° C. and stirred for 1.5 hours.
The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 100 ml of diethyl ether. This diluted solution was washed twice with 20 ml of 3N hydrochloric acid and once with 30 ml of saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to column chromatography and represented by the general formula 22 Among the compounds, 2.164 g of the compound (present compound 1-2) where X = F, Y = Cl, B = OH, R ² = CH ₃ , R ³ = H, and M = H were added to the following two types. Obtained as a mixture of isomers.
Isomer A
¹ H-NMR (300 MHz, acetone-d ₆ , TMS) δ (ppm): 1.34 (3H, d), 3.20 (1H, q), 7.08 (1H, d), 7.22 ( 1H, d), 7.72 (1H, brs), 9.68 (1H, brs)
Isomer B
¹ H-NMR (300 MHz, acetone-d ₆ , TMS) δ (ppm): 1.35 (3H, d), 3.20 (1H, q), 7.08 (1H, d), 7.19 ( 1H, d), 7.52 (1H, brs), 9.58 (1H, brs)

Production Example 1-2
Under a nitrogen stream, 2.00 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) (compound 3-1) was converted to 7.0 g of toluene. Dissolved. To this solution, 1.7 g of triethylamine and 1.1 g of methylmalonic acid were added, heated to 80 ° C. and stirred for 2 hours. After allowing the reaction solution to cool to room temperature, the precipitated crystals were filtered off, washed twice with 2.0 ml of toluene, and among the compounds represented by the general formula 22, X = F, Y = Cl, B = A compound (present compound 1-424) of OH, R ² = CH ₃ , R ³ = H, M = HN (C ₂ H ₅ ) ₃ was obtained.
¹ H-NMR (300 MHz, DMSO-d ₆ , TMS) δ (ppm): 1.0-1.4 (12H, m), 2.6-3.2 (7H, m), 6.8-7 .6 (3H, m) 9.9-10.3 (1H, m)
Production Example 1-3
To the compound 1-424 of the present invention obtained in Production Example 1-2, 100 ml of ethyl acetate and 50 ml of 10% hydrochloric acid were added to carry out a liquid separation operation. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. Among the compounds represented by the general formula 22, X = F, Y = Cl, B = OH, R ² = CH ₃ , R ³ = H, M = H 2.6 g of the compound (present compound 1-2) was obtained as a crude product.

Production Example 1-4
Under a nitrogen stream, 0.50 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (compound 3-3) was added to 3.0 ml of pyridine. Dissolved in. Piperidine (0.167 ml) and methylmalonic acid (0.199 g) were added to the solution, heated to 80 ° C. and stirred for 3.5 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 100 ml of diethyl ether. This diluted solution was washed twice with 20 ml of 3N hydrochloric acid and once with 30 ml of saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to column chromatography and represented by the general formula 22 Among the compounds, 0.467 g of a compound in which X = F, Y = Cl, B = OCH (CH ₃ ) ₂ , R ² = CH ₃ , R ³ = H, M = H (the present compound 1-5) is obtained. To obtain a mixture of the following two isomers.
Isomer A
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.32 (3H, d), 1.35 (3H, d), 1.37 (3H, d), 3.26 (1H, q), 4.48 (1H, m), 7.02-7.10 (2H, m), 7.25 (1H, brs), 8.04 (1H, brs)
Isomer B
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.35 to 1.43 (9H, m), 3.22 (1H, brq), 4.47 (1H, m), 6. 98 (1H, d), 7.07 (1H, d), 7.16 (1H, brs), 7.90 (1H, brs)
Production Example 1-5
3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (compound 3-3) 0.25 g was dissolved in ethanol 1.0 g. Then, 0.15 g of triethylamine and 0.18 g of methylmalonic acid were added and reacted at 80 ° C. for 3.5 hours to obtain Compound 1-5 of the present invention in a yield of 95% (internal standard using liquid chromatography). Check by law).

Production Example 1-6
3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (Compound 3-3) (3.0 g) was dissolved in toluene (10.0 g). . To this solution, 1.4 g of triethylamine and 1.6 g of methylmalonic acid were added, heated to 80 ° C. and stirred for 3.5 hours. After allowing the reaction solution to cool to room temperature, the precipitated crystals were separated by filtration, and among the compounds represented by the general formula 22, X = F, Y = Cl, B = OCH (CH ₃ ) ₂ , R ² = 2.85 g of a compound (present compound 1-427) of CH ₃ , R ³ = H, M = HN (C ₂ H ₅ ) ₃ was obtained.
¹ H-NMR (250 MHz, CDCl ₃ , TMS) δ (ppm): 1.1-1.5 (18H, m), 2.6-3.2 (7H, m), 4.4-4.7 (1H, m), 6.1 (1H, s), 6.9-7.2 (3H, m), 7.7 (1H, s), 10.9 (1H, s)
Production Example 1-7
Under a nitrogen stream, 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5- (1-methyl-2-propynyl) oxyphenylhydrazone) (Compound 3-5) 0.425 g was added to 3.0 ml toluene. To this solution were added 0.26 ml of triethylamine and 0.179 g of methylmalonic acid, and the mixture was stirred at 80 ° C. for 2 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and diluted with 100 ml of diethyl ether. This diluted solution was washed twice with 20 ml of 3N hydrochloric acid. The organic layer was washed once with 100 ml of a saturated aqueous sodium bicarbonate solution, the organic layer was removed, the residue was subjected to column chromatography, and among the compounds represented by the general formula 22, X = F, Y = Cl, B Two isomers (140 mg + 58 mg) of the compound (present compound 1-8) in which ═OCH (CH ₃ ) C≡CH, R ² ═CH ₃ , R ³ = H and M = H were obtained.
Isomer 1 (140 mg component)
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.35 (brd, 3H), 1.69 (d, 3H), 2.54 (s, 1H), 3.19 (brs, 1H), 4.83 (brd, 1H), 7.07 (d, 1H), 7.16 (brs, 1H), 7.28 (m, 1H), 7.98 (brs, 1H)
Isomer 2 (58 mg component)
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.34 (brd, 3H), 1.71 (m, 3H), 2.54 (m, 1H), 3.24 (brt, 1H), 4.86 (brq, 1H), 7.07 (d, 1H), 7.26 (m, 1H), 7.35 (brs, 1H), 8.09 (brd, 1H)

Production Example 1-8
Under a nitrogen stream, 0.466 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5- (ethoxycarbonyl) methoxyphenylhydrazone) (compound 3-8) was dissolved in toluene. Added to 5.0 ml. 0.46 ml of triethylamine and 0.356 g of methylmalonic acid were added to the solution, heated to 80 ° C. and stirred for 2 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and diluted with 100 ml of diethyl ether. This diluted solution was washed twice with 20 ml of 3N hydrochloric acid. The organic layer was extracted with 100 ml of saturated aqueous sodium hydrogen carbonate, and 3N hydrochloric acid was added to the aqueous layer until the pH reached 4. This aqueous layer was extracted with 100 ml of diethyl ether, and the organic layer was dried over magnesium sulfate and then concentrated under reduced pressure, whereby among the compounds represented by the general formula 22, X = F, Y = Cl, B = OCH ₂ 0.338 g of a compound (present compound 1-11) in which COOC ₂ H ₅ , R ₂ = CH ₃ , R ³ = H, M = H was obtained.
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.17 (t, 3H), 1.23 (d, 3H), 3.08 (q, 1H), 4.16 (q, 2H), 4.59 (s, 2H), 6.82 (d, 1H), 6.92 (d, 1H), 7.13 (s, 1H), 8.22 (s, 1H)
Production Example 1-9
Under nitrogen flow, 1.00 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (compound 3-3) was dissolved in 3 g of toluene. did. To this solution, 0.4 g of triethylamine and 0.4 g of malonic acid were added, heated to 80 ° C. and stirred for 3.5 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 30 ml of ethyl acetate.
This diluted solution was washed once with 20 ml of 10% hydrochloric acid, dried over magnesium sulfate, filtered, concentrated under reduced pressure, the residue was subjected to column chromatography, and among the compounds represented by the general formula 22, X = F Y = Cl, B = OCH (CH ₃ ) ₂ , R ² = H, R ³ = H, M = H (0.9 g of the present compound 1-65) was obtained.
¹ H-NMR (250 MHz, CDCl ₃ , TMS) δ (ppm): 1.31 (d, 3H), 1.37 (d, 3H), 2.91 (d, 1H), 3.14 (d, 1H), 4.30 -4.50 (m, 1H), 6.96 (d, 1H), 7.04 (s, 1H), 7.06 (d, 1H), 7.57 (brs, 1H)

Production Example 1-10
3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (compound 3-3) 0.65 g, ethylmalonic acid 0.53 g was triethylamine After dissolving in 4.0 ml and stirring for 30 minutes at room temperature, the mixture was heated to reflux for 1.5 hours. After the reaction solution was allowed to cool to room temperature, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography, and among the compounds represented by general formula 22, X = F, Y = Cl, B = OCH (CH ₃ ) ₂ , R ² = CH ₂ CH ₃ , R ³ = H, A compound in which M = H (the present compound 1-153) was obtained as a crude product.
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.03 (3H, t), 1.37 (6H, d), 1.81 (2H, m), 3.05 (1H, m), 4.48 (1H, m), 6.98 (1H, d), 7.08 (1H, d), 7.15 (1H, s) 7.90 (1H, brs)

2) Production Example of Pyridazin-3-one Derivative from the Compound of the Present Invention (Process 2 of the Present Invention)
Production Example 2-1
The present compound (1-2) (0.315 g) was dissolved in 1.0 ml of acetic acid and 1.0 ml of pyridine under a nitrogen stream and stirred at 120 ° C. for 8 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 100 ml of diethyl ether. The diluted solution was washed twice with 20 ml of 3N hydrochloric acid and once with 30 ml of saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to column chromatography, and 2- (2-fluoro- 0.227 g of 4-chloro-5-hydroxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-1) was obtained. (Mp 177.6 ° C)

Production Example 2-2
0.5025 g of the present compound (1-2) is dissolved in 2.0 ml of propionic acid and heated at 130 ° C. for 7.5 hours to give 2- (2-fluoro-4-chloro-5-hydroxyphenyl) -4- The yield of methyl-5-trifluoromethylpyridazin-3-one (compound 5-1) was 54.6% (the yield was calculated by the LC-ES method. LC-ES method; The detection intensity by liquid chromatography analysis at a constant concentration is measured, and then the solution obtained by adjusting the reaction solution after completion of the reaction to a constant concentration is subjected to liquid chromatography analysis under the same conditions to measure the detection intensity of the target product. This is a method for calculating the concentration of the target substance in the reaction solution by comparing the detected intensities.
Production Example 2-3
27.87 g of the compound (1-2) of the present invention is dissolved in 551.94 g of chlorobenzene, 44.18 g of 5-ethyl-2-methylpyridine and 16 ml of valeric acid are added, and azeotropic dehydration is carried out under heating reflux for 24 hours. (2-Fluoro-4-chloro-5-hydroxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-1) yield 73.7% (LC-ES method) was obtained. .

Production Example 2-4
20.94 g of the present compound (1-2) is dissolved in 26.18 g of toluene, 13.32 g of 5-ethyl-2-methylpyridine and 8.16 g of propionic acid are added, and the mixture is azeotropically heated under reflux for 22.5 hours. Dehydrated 2- (2-fluoro-4-chloro-5-hydroxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-1) yield 74.2% (LC-ES method) )
Production Example 2-5
The present compound (1-2) (0.1182 g) is dissolved in chlorobenzene (3.0 g), 5-ethyl-2-methylpyridine (0.0498 g) is added, and the mixture is heated under reflux for 21.5 hours to give 2- (2-fluoro-4 -Chloro-5-hydroxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-1) Yield 58.2% (LC-ES method) was obtained.

Production Example 2-6
Dissolve 0.3469 g of the compound (1-2) of the present invention in 5.0 ml of chlorobenzene, add 0.38 ml of 5-ethyl-2-methylpyridine and a catalytic amount of N, N-dimethylformamide, and further thionyl chloride at 30 ° C. 0.14 ml was added and stirred at 60 ° C. for 1 hour to give 2- (2-fluoro-4-chloro-5-hydroxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-1 ) Yield 45.0% (LC-ES method) was obtained.
Production Example 2-7
This invention compound (1-5) 1.0g was melt | dissolved in 3 ml of xylene, and it heated and refluxed for 4 hours. After allowing the reaction solution to cool to room temperature, the reaction solution is concentrated under reduced pressure, the residue is subjected to column chromatography, and 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl- 0.36 g of 5-trifluoromethylpyridazin-3-one (Compound 5-2) was obtained.
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.38 (6H, d, J = 6.3 Hz), 2.43 (3H, q, J = 2.0 Hz), 4.47 (1H, m), 6.99 (1H, d, J = 5.0 Hz), 7.29 (1H, d, J = 9.5 Hz), 8.00 (1H, s)

Production Example 2-8
0.467 g of the present compound (1-5) was dissolved in 2.0 ml of acetic acid under a nitrogen stream and stirred at 120 ° C. for 11.5 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 100 ml of diethyl ether. This diluted solution was washed once with 30 ml of saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was subjected to column chromatography, and 2- (2-fluoro-4-chloro-5-isopropoxy) was obtained. Phenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-2) (0.334 g) was obtained.
Production Example 2-9
The present compound (1-5) (0.512 g) is dissolved in xylene (2.0 g), 4-nitrobenzoic acid (0.215 g) is added, and the mixture is stirred with heating under reflux for 6 hours to give 2- (2-fluoro-4-chloro- 5-Isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-2) was obtained in a yield of 56% (confirmed by internal standard method using liquid chromatography).
Production Example 2-10
This invention compound (1-5) 15.0g is melt | dissolved in xylene 75.0g, p-toluenesulfonic acid monohydrate 0.72g is added, and it stirs at 81 degreeC for 15 hours, 2- (2-fluoro-4 -Chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-2) was obtained in 49% yield (confirmed by internal standard method using liquid chromatography) ).

Production Example 2-11
5.0 g of the present compound (1-5) was dissolved in 25 g of xylene, 2.3 g of tri-n-butylamine was added, and the mixture was refluxed at 145 to 160 ° C. for 26 hours while dehydrating with molecular sieve 3A. After completion of the reaction, the reaction solution was allowed to cool to room temperature, and then ethyl acetate and 10% hydrochloric acid were added, followed by a liquid separation operation. After drying the organic layer, the residue obtained by concentration was subjected to column chromatography to give 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazine. 3.4 g of -3-one (compound 5-2) was obtained.
Production Example 2-12
This invention compound (1-5) 15.04g is melt | dissolved in xylene 75.12g, 3.84g of triethylamines are added, and it stirs at 132 degreeC for 21 hours, spin-dry | dehydrates using molecular Sibu 3A, 2- (2- Fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-2) was obtained in 71% yield (internal standard using liquid chromatography) Check by law).

Production Example 2-13
This invention compound (1-5) 14.99g is melt | dissolved in xylene 74.9g, 4-picoline 3.49g is added, and it stirs at 131-137 degreeC for 26 hours, dehydrating using a Dean-Stark trap. 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-2) was obtained in a yield of 85% (liquid (Confirmed by internal standard method using chromatography).
Production Example 2-14
0.25 g of the present compound (1-5) is dissolved in 1.0 g of xylene at room temperature, 0.14 g of quinoline is added, and the mixture is heated under reflux for 4 hours. 2- (2-Fluoro-4-chloro-5-isopropoxyphenyl) ) -4-Methyl-5-trifluoromethylpyridazin-3-one (Compound 5-2) was obtained in a yield of 55% (confirmed by internal standard method using liquid chromatography).
Production Example 2-15
0.25 g of the present compound (1-5) is dissolved in 1.0 g of xylene at room temperature, 0.09 g of N, N-dimethylaniline is added, and the mixture is heated under reflux for 4 hours to give 2- (2-fluoro-4 -Chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-2) was obtained in 60% yield (confirmed by internal standard method using liquid chromatography) ).
Production Example 2-16
This invention compound (1-5) 15.05g is melt | dissolved in acetic acid 6.03g and pyridine 29.45g, and it stirs at 127 degreeC for 8 hours, 2- (2-fluoro-4-chloro-5-isopropoxyphenyl)- 4-Methyl-5-trifluoromethylpyridazin-3-one (Compound 5-2) was obtained in a yield of 82% (confirmed by internal standard method using liquid chromatography).

Production Example 2-17
5.00 g of the present compound (1-5) is dissolved in 25 g of xylene, 0.919 g of propionic acid and 1.159 g of 4-picoline are added, and the mixture is stirred at 142 ° C. for 13.5 hours while dehydrating using Molecular Sibu 3A. 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-2) was obtained in a yield of 90.1%. (Confirmed by internal standard method using liquid chromatography).
Production Example 2-18
Dissolve 5.001 g of the present compound (1-5) in 25 g of xylene, add 2.084 g of 4-nitrobenzoic acid and 1.160 g of 4-picoline, and dehydrate using Molecular Sibu 3A at 148 ° C. for 6 hours. Stir to give 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-2) in 93.5% yield. (Confirmed by internal standard method using liquid chromatography).
Production Example 2-19
6.77 g of the present compound (1-5) is dissolved in 59 g of xylene, mixed with 2.45 g of 5-ethyl-2-methylpyridine, 1.25 g of propionic acid and 0.68 g of calcium carbonate, and heated under reflux for 10 hours. Azeotropic dehydration. After completion of the reaction, the reaction solution was cooled to room temperature, poured into 20% 5% hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with 20 ml of 20% brine, dried over anhydrous sodium sulfate and concentrated. The obtained residue was purified by silica gel column chromatography to give 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-2). 4.91 g (80%) was obtained.
Production Method 2-20
0.5 g of the present compound (1-5) was dissolved in 10 ml of tetrahydrofuran, 0.25 g of triethylamine was added to the solution, and the mixture was stirred at 30 ° C. for 10 minutes. Thereafter, a solution of 0.2 g of ethyl chloroformate dissolved in 3 ml of tetrahydrofuran at the same temperature was added dropwise over 20 minutes.
After completion of the dropwise addition, the reaction solution was poured into water and extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid, dried over magnesium sulfate and concentrated. The residue was subjected to column chromatography to give 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5. -Obtained 0.19 g of trifluoromethylpyridazin-3-one (compound 5-2).

Production Example 2-21
0.25 g of the present compound (1-427) is dissolved in 2.0 g of xylene and heated under reflux for 9 hours to give 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -4-methyl-5- Trifluoromethylpyridazin-3-one (Compound 5-2) was obtained in a yield of 20% (confirmed by internal standard method using liquid chromatography).
Production Example 2-22
1 ml of pyridine and 1 ml of acetic acid were added to 0.198 g of the present compound (1-8), and the mixture was stirred at 120 ° C. for 5 hours. The reaction solution was allowed to cool to room temperature and then concentrated under reduced pressure. The residue was subjected to column chromatography to give 2- (4-chloro-2-fluoro-5-((1-methyl-2-propynyl) oxy). 0.086 g of (phenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-4) was obtained.
m. p. 114.1 ° C
Production Example 2-23
1 ml of pyridine and 1 ml of acetic acid were added to 0.321 g of the present compound (1-11), and the mixture was stirred at 120 ° C. for 5 hours. The reaction solution is allowed to cool to room temperature and then concentrated under reduced pressure. The residue is subjected to column chromatography to give 2- (2-chloro-4-fluoro-5- (5-methyl-6-oxo-4-trimethyl). 0.189 g of ethyl fluoromethyl-1,6-dihydro-1-pyridazinyl) phenoxy) acetate (Compound 5-6) was obtained.
m. p. 102.0 ° C

Production Example 2-24
A mixture of 2.03 g of the present compound (1-153) with 2.0 ml of acetic acid and 1.0 ml of pyridine was heated to reflux for 3 hours. After allowing the reaction solution to cool to room temperature, acetic acid and pyridine are distilled off under reduced pressure, and the residue is subjected to silica gel column chromatography to give 2- (4-chloro-2-fluoro-5-isopropoxyphenyl) -4-ethyl. 84 mg of -5-trifluoromethylpyridazin-3-one (Compound 5-9) was obtained.
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.26 (t, 3H, J = 7.5 Hz), 1.38 (d, 6H, J = 6.2 Hz), 2.86 (Dq, 2H, J = 7.5 Hz, 1.3 Hz), 4.49 (qq, 1H, J = 6.2 Hz, 6.2 Hz), 7.00 (d, 1H, J = 6.5 Hz), 7.29 (d, 1H, J = 9.3 Hz), 7.99 (s, 1H)
Production Example 2-25
1.0 g of the present compound (1-65) was dissolved in 4.35 g of acetic acid and 2.17 g of pyridine and stirred at 120 ° C. for 8.5 hours. After allowing to cool to room temperature, the reaction mixture was poured into dilute hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, and concentrated to obtain a crude product. This crude product was subjected to column chromatography to obtain 0.47 g of 2- (2-fluoro-4-chloro-5-isopropoxyphenyl) -5-trifluoromethylpyridazin-3-one (compound 5-10). It was.
m. p. 68.6 ° C

3) Process for producing the compound of the present invention without isolation Production Example 3-1
Pyridine 2 was added 0.295 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-hydroxyphenylhydrazone) (Compound 3-1) at room temperature under a nitrogen stream. Dissolved in 0.0 ml. To this solution, 0.113 ml of piperidine and 0.295 g of methylmalonic acid were added, heated to 70 ° C. and stirred for 2.5 hours, then 2.0 ml of acetic acid was added, and stirring was further continued at 130 ° C. for 7 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 100 ml of diethyl ether. This diluted solution was washed twice with 20 ml of 3N hydrochloric acid and once with 30 ml of saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to column chromatography, and 2- (2-fluoro- 0.184 g of 4-chloro-5-hydroxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (Compound 5-1) was obtained.
Production Example 3-2
Under nitrogen flow at room temperature, 3,99,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (compound 3-3) 0.399 g was pyridine Dissolved in 2.4 ml. To the solution, 0.133 ml of piperidine and 0.159 g of methylmalonic acid were added, heated to 70 ° C. and stirred for 3.5 hours, then 2.4 ml of acetic acid was added, and stirring was continued at 130 ° C. for 8 hours. The reaction solution was allowed to cool to room temperature, concentrated under reduced pressure, and the residue was diluted with 100 ml of diethyl ether. This diluted solution was washed twice with 20 ml of 3N hydrochloric acid and once with 30 ml of saturated aqueous sodium hydrogen carbonate, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to column chromatography, and 2- (2-fluoro- 4-chloro-5-isopropoxyphenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-2) 0.255 g was obtained.

Production Example 3-3
3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5- (carboxymethoxy) phenylhydrazone) (compound 3-6) 0.62 g was dissolved in 4.6 ml of pyridine. Then, 0.5 g of methylmalonic acid and 0.14 g of piperidine were added, and the mixture was stirred at 70 ° C. for 3 hours. Thereafter, 4.6 ml of acetic acid was added and stirred at an external temperature of 130 ° C. for 10 hours. After completion of the reaction, the reaction solution was poured into water, and the solution was extracted with diethyl ether. The organic layer was washed successively with water and dilute hydrochloric acid, dried over anhydrous magnesium sulfate, diethyl ether was distilled off, and the resulting crystals were recrystallized from a solvent of hexane: diethyl ether = 3: 1. 0.34 g of (2-fluoro-4-chloro-5- (carboxymethoxy) phenyl) -4-methyl-5-trifluoromethylpyridazin-3-one (compound 5-11) was obtained.
Production Example 3-4
0.25 g of 3,3,3-trifluoro-2-oxopropanal 1- (4-chlorophenylhydrazone) (compound 3-11) was dissolved in 2 ml of pyridine, 0.24 g of methylmalonic acid and piperidine were dissolved in the solution. 0.09g was added and it stirred at 80 degreeC for 4 hours. Thereafter, 2.0 ml of acetic acid was added to the reaction solution, followed by stirring at 80 ° C. for 6.5 hours and further at 120 ° C. for 4 hours. After completion of the reaction, the reaction solution was poured into water and extracted with diethyl ether. The organic layer was washed successively with water and dilute hydrochloric acid, dried over anhydrous magnesium sulfate, diethyl ether was distilled off, the residue was subjected to silica gel column chromatography, 2- (4-chlorophenyl) -4-methyl-5- 0.15 g of trifluoromethylpyridazin-3-one (Compound 5-12) was obtained.
m. p. 80.8 ℃

Next, the synthesis method of the raw material compound used in the present invention step 1 will be described with reference examples.
Reference example 1
To a solution obtained by mixing 5.3 g (53.5 mmol) of sodium acetate and about 100 ml of water, 6.6 g (24.3 mmol) of 1,1-dibromo-3,3,3-trifluoroacetone was added under ice-cooling. The reaction was carried out at 20 ° C. for 20 minutes. Next, the reaction solution was allowed to cool to room temperature, and a solution of 5.8 g (21.5 mmol) of 2-fluoro-4-chloro-5-isopropoxyphenylhydrazine dissolved in about 20 ml of diethyl ether was added thereto. Stir for 1 hour. The organic layer was separated, washed once with 10 ml of saturated brine, dried over anhydrous magnesium sulfate, and then diethyl ether was distilled off to give 3,3,3-trifluoro-2-oxo-propanal 1 6.5 g (20.0 mmol) of-(4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) (compound 3-3) was obtained.
¹ H-NMR [250 MHz, CDCl ₃ , TMS, δ (ppm)] 1.39 (6H, d, J = 6.0 Hz), 4.38-4.52 (1H, m), 7.15 (1H, d, J = 10.5 Hz), 7.22 (1H, d, J = 7.3Hz), 7.43 (1H, q, J = 1.7Hz), 9.18 (1H, brs)
Reference example 2
32.3 g of 5-amino-2-chloro-4-fluorophenol (the compound was prepared according to the method described in European Patent Application Publication No. EP-61741-A) was mixed with 150 ml of concentrated hydrochloric acid. And stirred at 50 ° C. for 30 minutes. A solution prepared by dissolving 15 g of sodium nitrite in 40 ml of water was added dropwise to the mixture at 0 ° C. over 10 minutes. After stirring at 0 ° C. for 1 hour, the reaction solution was cooled to −50 ° C., and a solution of 132 g stannous chloride dissolved in 132 g concentrated hydrochloric acid was quickly added dropwise at −50 ° C., gradually returned to room temperature, and stirred for 1 hour. did. The resulting solid was collected by filtration and dried at 80 ° C. under reduced pressure to obtain 75 g of crude crystals of 2-fluoro-4-chloro-5-hydroxyphenylhydrazone hydrochloride.
¹ H-NMR [DMSO-d ₆ , TMS, δ (ppm)] 3 to 5 (2H, br), 6.73 (1H, d), 7.22 (1H, d), 8.20 (1H, s), 9 to 11 (2H, brs)
49.2 g of sodium acetate and 40.5 g of 1,1-dibromo-3,3,3-trifluoroacetone were dissolved in 400 ml of water and heated at 80 to 90 ° C. for 40 minutes. The solution was cooled to 0 ° C., and 75 g of crude crystals of 2-fluoro-4-chloro-5-hydroxyphenylhydrazine hydrochloride obtained by the method described above were added. The reaction mixture was stirred at room temperature for 70 minutes, and the resulting crystals were collected and dried under reduced pressure to give 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5- 35.4 g of (hydroxyphenylhydrazone) (compound 3-1) was obtained.
¹ H-NMR [300 MHz, CDCl ₃ , TMS δ (ppm)] 5.49 (s, 1H), 7.15 (d, J = 10.5 Hz, 1H), 7.24 (d, J = 7.4 Hz, 1H), 7.38 (q , J = 1.8Hz, 1H), 8.75 (s, 1H)

４，４，４−トリフルオロアセト酢酸エチル２０．１ｇと酢酸ナトリウム２５ｇを水１５０ｍｌに溶解させた溶液に、化合物［Ｉ−１］から誘導されるジアゾニウム塩酸溶液（４−クロロ−２−フルオロ−５−イソプロポキシアニリン２０．３ｇ、濃塩酸２０ｍｌ、水２０ｍｌおよび亜硝酸ナトリウム７．３ｇから調製）を１０℃以下の温度で滴下した。滴下終了後、１時間室温で攪拌した後、生じた結晶を濾集し、水で洗浄した後、乾燥し、スキ−ム化１６中の化合物［ＩＩ−１］３４ｇを結晶として得た。（収率８５％）
１，４−ジオキサン３０ｍｌと水３ｍｌ中に上記反応で得られた化合物［ＩＩ−１］１５．９ｇと水酸化リチウム１水和物１．７ｇを加え、６時間加熱還流した。反応液を氷水に注加し、希塩酸で中和した後、酢酸エチルで抽出し、有機層を乾燥した後、濃縮した。残渣をヘキサンで洗浄し、化合物［ＩＩＩ−１］１１．３ｇを得た。（収率７６．３％）
上記反応で得られた化合物［ＩＩＩ−１］７．４ｇをＮ，Ｎ−ジメチルホルムアミド４２ｍｌに溶解し、１００℃に反応液を昇温し、そのまま３０分間保温した。その後室温まで冷却し、反応液を水に注加し、酢酸エチルで抽出した。有機層を希塩酸水で洗浄し、無水硫酸マグネシウムで乾燥後、濃縮して、（化合物３−３：スキーム化２５における化合物［ＩＶ−１］）５．９ｇを得た。（収率９０％）
¹Ｈ−ＮＭＲ[ 250MHz、ＣＤＣｌ₃、TMS 、δ(ppm)] 1.39(6H, d, J=6.0Hz) 、4.38〜4.52(1H, m) 、7.15(1H, d, J=10.5Hz) 、7.22(1H, d, J=7.3Hz)、7.43(1H, q, J=1.7Hz)、9.18(1H, br) Reference example 3
The following manufacturing method based on scheme 25
[ Chemical Formula 25 ]

A solution of 20.1 g of ethyl 4,4,4-trifluoroacetoacetate and 25 g of sodium acetate in 150 ml of water was dissolved in a diazonium hydrochloric acid solution (4-chloro-2-fluoro-) derived from compound [I-1]. 5-isopropoxyaniline (20.3 g), concentrated hydrochloric acid (20 ml), water (20 ml) and sodium nitrite (7.3 g) were added dropwise at a temperature of 10 ° C or lower. After completion of the dropwise addition, the resulting crystals were stirred for 1 hour at room temperature, and the resulting crystals were collected by filtration, washed with water, and dried to obtain 34 g of Compound [II-1] in scheme 16 as crystals. (Yield 85%)
15.9 g of the compound [II-1] obtained by the above reaction and 1.7 g of lithium hydroxide monohydrate were added to 30 ml of 1,4-dioxane and 3 ml of water, and the mixture was heated to reflux for 6 hours. The reaction solution was poured into ice water, neutralized with dilute hydrochloric acid, extracted with ethyl acetate, the organic layer was dried and concentrated. The residue was washed with hexane to obtain 11.3 g of compound [III-1]. (Yield 76.3%)
7.4 g of the compound [III-1] obtained by the above reaction was dissolved in 42 ml of N, N-dimethylformamide, the temperature of the reaction solution was raised to 100 ° C., and the temperature was kept for 30 minutes. After cooling to room temperature, the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, dried over anhydrous magnesium sulfate, and concentrated to obtain 5.9 g of (Compound 3-3: Compound [IV-1] in Scheme 25). (Yield 90%)
¹ H-NMR [250 MHz, CDCl ₃ , TMS, δ (ppm)] 1.39 (6H, d, J = 6.0 Hz), 4.38 to 4.52 (1H, m), 7.15 (1H, d, J = 10.5 Hz), 7.22 (1H, d, J = 7.3Hz), 7.43 (1H, q, J = 1.7Hz), 9.18 (1H, br)

参考例３の方法に準じて、化合物［Ｉ−２］から化合物［ＩＩ−２］を製造した。
（反応１）１，４−ジオキサン３０ｍｌと水２ｍｌとの混合液に化合物［ＩＩ−２］５．０ｇと水酸化リチウム１水和物０．６７ｇを加え、１．５時間加熱還流した。反応液を氷水に注加し、希塩酸で中和した後、酢酸エチルで抽出した。抽出液を乾燥した後、濃縮した。得られた結晶をヘキサン−ジエチルエ−テル混合溶媒（ヘキサン：ジエチルエ−テル＝２：１）で洗浄して化合物［ＩＩＩ−２］３．３ｇを得た。（収率７３％）
（反応２） 上記（反応１）に準じて得られた化合物［ＩＩＩ−２］３．３ｇをジメチルスルホキシド１０ｍｌに溶解させ、反応液を１００℃に昇温し、そのまま１０分間保温した。その後室温まで冷却し、反応液をそのままシリカゲルカラムクロマトグラフィ−（展開溶媒；ヘキサン：酢酸エチル＝７：１）に付し、化合物［ＩＶ−２］２．５５ｇを得た。（収率９１％）
（反応３）トルエン４０ｍｌ中に、上記（反応１）に準じて得られた化合物［ＩＩＩ−２］５．０ｇ、キノリン０．５ｍｌおよび銅粉０．１ｇを加えた反応溶液を１００℃に昇温し、そのまま２０分間保温した。反応液を室温まで冷却し、そのままシリカゲルカラムクロマトグラフィ−（展開溶媒；ヘキサン：酢酸エチル＝８：１）に付し、（化合物３−１１：スキーム化２６における化合物［ＩＶ−２］）３．６ｇを得た。（収率８６％） Reference example 4
Manufacturing method based on the following scheme 26
[ Chemical formula 26 ]

According to the method of Reference Example 3, compound [II-2] was produced from compound [I-2].
(Reaction 1) To a mixed solution of 30 ml of 1,4-dioxane and 2 ml of water, 5.0 g of compound [II-2] and 0.67 g of lithium hydroxide monohydrate were added and heated under reflux for 1.5 hours. The reaction solution was poured into ice water, neutralized with dilute hydrochloric acid, and extracted with ethyl acetate. The extract was dried and concentrated. The obtained crystals were washed with a hexane-diethyl ether mixed solvent (hexane: diethyl ether = 2: 1) to obtain 3.3 g of compound [III-2]. (Yield 73%)
(Reaction 2) 3.3 g of the compound [III-2] obtained according to the above (Reaction 1) was dissolved in 10 ml of dimethyl sulfoxide, the temperature of the reaction solution was raised to 100 ° C., and the temperature was kept for 10 minutes. Thereafter, the mixture was cooled to room temperature, and the reaction solution was subjected to silica gel column chromatography (developing solvent; hexane: ethyl acetate = 7: 1) as it was to obtain 2.55 g of compound [IV-2]. (Yield 91%)
(Reaction 3) A reaction solution obtained by adding 5.0 g of compound [III-2] obtained according to the above (Reaction 1), 0.5 ml of quinoline and 0.1 g of copper powder in 40 ml of toluene was heated to 100 ° C. Warm and keep warm for 20 minutes. The reaction solution was cooled to room temperature and directly subjected to silica gel column chromatography (developing solvent: hexane: ethyl acetate = 8: 1) to give 3.6 g of (Compound 3-11: Compound [IV-2] in Scheme 26). Got. (Yield 86%)

５−アミノ−２−クロロ−４−フルオロフェノキシ酢酸エチル２４．７ｇを水４０mlに懸濁させて室温で濃塩酸４０mlを滴下し、３０分間攪拌した。この溶液を０℃まで冷却し、亜硝酸ナトリウム７．６ｇを水２０mlに溶解させた溶液を５℃以下で滴下した後、さらに1時間攪拌した。上記操作で得られたジアゾニウム溶液を、４，４，４−トリフルオロアセト酢酸エチル２１ｇ、酢酸ナトリウム５２ｇ、水105 ｍｌからなる水溶液へ、１０℃以下で滴下し、３０分間攪拌した。
その後、析出した結晶をロ取し、その結晶を酢酸エチルに溶解させ、溶媒を硫酸マグネシウムで乾燥させた後減圧濃縮し、得られた残査をシリカゲルクロマトグラフィ−に付し、化合物［ＩＩ−３］１９．５ｇを得た。
¹Ｈ−ＮＭＲ[ 250MHz、ＣＤＣｌ₃、TMS 、δ(ppm)] 1.31(3H, t, J=7.16Hz)、1.42(3H, t,J=7.1Hz) 、4.27(2H, q, J=7.16Hz) 、4.43(2H, q, J=7.12Hz) 、4.72(2H, s) 、7.18(1H, d, J=6.73Hz) 、7.27(1H, d, J=10.0Hz)
上記反応で得られた化合物［ＩＩ−３］４．４ｇを１，４−ジオキサン２０ｍｌに溶解し、水酸化リチウム１水和物１．２６ｇを加えて３時間還流した。反応終了後、反応液を水にあけ、酢酸エチルで水層を洗浄した。水層に希塩酸を加えて酸性とした後、酢酸エチルで抽出し、有機層を水洗した後、硫酸マグネシウムで乾燥させ、溶媒を減圧濃縮して、化合物［ＩＩＩ−３］２．９２ｇを得た。
¹Ｈ−ＮＭＲ[ 250MHz、ＣＤＣｌ₃、TMS 、δ(ppm)]4.78(2H, s) 、7.25(1H, d, J=6.42Hz) 、7.35(1H, d, J=9.82Hz)
上記反応で得られた化合物［ＩＩＩ−３］２．５ｇをピリジン１０ｍｌに溶解し、１００℃で１時間攪拌した。反応終了後、反応液を水にあけ、ジエチルエ−テルで抽出し、有機層を希塩酸で洗浄後、硫酸マグネシウムで乾燥させ、溶媒を減圧濃縮し、（化合物３−６：スキーム化２７における化合物［ＩＶ−３］）で示される、３，３，３−トリフルオロ−２−オキソプロパナ−ル１−［４−クロロ−２−フルオロ−５−（カルボキシメトキシ）フェニルヒドラゾン］１．８１ｇを得た。
¹Ｈ−ＮＭＲ[ 250MHz、ＣＤＣｌ₃、TMS 、δ(ppm)]4.77(2H, s) 、7.25(1H, d, J=10.1Hz) 、7.30(1H, d, J=6.75Hz) 、7.44(1H, s) Reference Example 5
Manufacturing method based on the following scheme 27
[ Chemical 27 ]

24.7 g of ethyl 5-amino-2-chloro-4-fluorophenoxyacetate was suspended in 40 ml of water, 40 ml of concentrated hydrochloric acid was added dropwise at room temperature, and the mixture was stirred for 30 minutes. The solution was cooled to 0 ° C., a solution prepared by dissolving 7.6 g of sodium nitrite in 20 ml of water was added dropwise at 5 ° C. or lower, and the mixture was further stirred for 1 hour. The diazonium solution obtained by the above operation was added dropwise to an aqueous solution composed of 21 g of ethyl 4,4,4-trifluoroacetoacetate, 52 g of sodium acetate, and 105 ml of water at 10 ° C. or lower and stirred for 30 minutes.
Thereafter, the precipitated crystals are collected, and the crystals are dissolved in ethyl acetate. The solvent is dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue is subjected to silica gel chromatography to give compound [II-3 ] 19.5 g was obtained.
¹ H-NMR [250 MHz, CDCl ₃ , TMS, δ (ppm)] 1.31 (3H, t, J = 7.16 Hz), 1.42 (3H, t, J = 7.1 Hz), 4.27 (2H, q, J = 7.16) Hz), 4.43 (2H, q, J = 7.12Hz), 4.72 (2H, s), 7.18 (1H, d, J = 6.73Hz), 7.27 (1H, d, J = 10.0Hz)
4.4 g of the compound [II-3] obtained by the above reaction was dissolved in 20 ml of 1,4-dioxane, 1.26 g of lithium hydroxide monohydrate was added, and the mixture was refluxed for 3 hours. After completion of the reaction, the reaction solution was poured into water, and the aqueous layer was washed with ethyl acetate. The aqueous layer was acidified with dilute hydrochloric acid, extracted with ethyl acetate, the organic layer was washed with water, dried over magnesium sulfate, and the solvent was concentrated under reduced pressure to obtain 2.92 g of compound [III-3]. .
¹ H-NMR [250 MHz, CDCl ₃ , TMS, δ (ppm)] 4.78 (2H, s), 7.25 (1H, d, J = 6.42 Hz), 7.35 (1H, d, J = 9.82 Hz)
2.5 g of the compound [III-3] obtained by the above reaction was dissolved in 10 ml of pyridine and stirred at 100 ° C. for 1 hour. After completion of the reaction, the reaction mixture was poured into water and extracted with diethyl ether. The organic layer was washed with dilute hydrochloric acid and dried over magnesium sulfate, and the solvent was concentrated under reduced pressure. (Compound 3-6: Compound [Scheme 27] IV-3]), which was 1.81 g of 3,3,3-trifluoro-2-oxopropanal 1- [4-chloro-2-fluoro-5- (carboxymethoxy) phenylhydrazone].
¹ H-NMR [250 MHz, CDCl ₃ , TMS, δ (ppm)] 4.77 (2H, s), 7.25 (1H, d, J = 10.1 Hz), 7.30 (1H, d, J = 6.75 Hz), 7.44 ( 1H, s)

Reference Example 6
To a solution obtained by mixing 1.249 g of sodium acetate and 10 ml of water, 1.366 g of 1,1-dibromo-3,3,3-trifluoroacetone was added and stirred at 80 ° C. for 30 minutes. The reaction solution was allowed to cool to room temperature, and then a solution prepared by dissolving 1.00 g of 4-chloro-2-fluoro-5- (ethoxycarbonyl) methoxyphenylhydrazine in 10 ml of diethyl ether was added, and the mixture was stirred at room temperature for 2 hours. Thereafter, the reaction solution was extracted with 100 ml of ethyl acetate, and the organic layer was washed with 100 ml of saturated aqueous sodium bicarbonate and 100 ml of saturated brine, dried over anhydrous magnesium sulfate and concentrated to obtain a crude product. This crude product was recrystallized from toluene to give 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5- (ethoxycarbonyl) methoxyphenylphenylhydrazone) (compound 3 -8) 1.151 g was obtained.
¹ H-NMR (250 MHz, CDCl ₃ , TMS) δ (ppm): 1.32 (t, 3H), 4.29 (q, 2H), 4.71 (s, 2H), 7.06 (d, 1H), 7.20 (d, 1H), 7.36 (m, 1H), 8.77 (brs, 1H)
Reference Example 7
To a solution obtained by mixing 2.870 g of sodium acetate and 20 ml of water, 3.139 g of 1,1-dibromo-3,3,3-trifluoroacetone was added and stirred at 80 ° C. for 30 minutes. The reaction solution was allowed to cool to room temperature, and then a solution prepared by dissolving 2.000 g of 4-chloro-2-fluoro-5- (1-methyl-2-propynyl) oxyphenylhydrazine in 10 ml of diethyl ether was added at room temperature. Stir for 2 hours. After completion of the reaction, the reaction solution was extracted with 100 ml of ethyl acetate, and the organic layer was washed successively with 100 ml of saturated aqueous sodium bicarbonate and 100 ml of saturated brine, dried over anhydrous magnesium sulfate and concentrated to obtain a crude product. The crude product was recrystallized from toluene and 3,3,3-trifluoro-2-oxopropanal 1- (4-chloro-2-fluoro-5- (1-methyl-2-propynyl) 2.120 g of (oxyphenylphenylhydrazone) (compound 3-5) was obtained.
¹ H-NMR (300 MHz, CDCl ₃ , TMS) δ (ppm): 1.74 (d, 3H), 2.55 (d, 1H), 4.83 (m, 1H), 7.17 (d, 1H), 7.39 (m, 1H), 7.53 (d, 1H), 8.91 (brs, 1H)
Reference Example 8
To a mixed solution of 5.3 g of sodium acetate and 100 ml of water, 4.4 g of 1,1-dichloro-3,3,3-trifluoroacetone was added under ice cooling, and the mixture was reacted at 90 ° C. for 30 minutes. Next, after the reaction solution was allowed to cool to room temperature, a solution prepared by dissolving 5.8 g of 2-fluoro-4-chloro-5-isopropoxyphenylhydrazine in 20 ml of diethyl ether was added thereto, followed by stirring at room temperature for 1 hour. The organic layer was separated, washed once with 10 ml of saturated brine, and dried over anhydrous magnesium sulfate. Diethyl ether was distilled off, and 3,3,3-trifluoro-2-oxopropanal 1- ( 6.5 g (Compound 3-3) of 4-chloro-2-fluoro-5-isopropoxyphenylhydrazone) was obtained.

Reference Example 9
9.340 g of ethyl 5-amino-2-chloro-4-fluorophenoxyacetate was added to 30 ml of 36% hydrochloric acid and stirred at 28 ° C. for 1 hour. A solution prepared by dissolving 2.642 g of sodium nitrite in 8 ml of water at 0 ° C. was added dropwise to this suspension solution over 10 minutes, and further stirred at 0 ° C. for 1 hour to prepare a diazonium salt solution. The diazonium salt solution prepared while cooling 25.34 g of 36% hydrochloric acid solution of 25.34 g of tin (II) chloride to 0 ° C. and stirring vigorously was further added dropwise, and further stirred at 0 ° C. to room temperature for 1 hour.
After completion of the reaction, the reaction solution was neutralized to pH 7 by adding a 30% aqueous sodium hydroxide solution, and extracted with diethyl ether. The organic layer was dried over magnesium sulfate and concentrated to obtain 1.840 g of ethyl 2-chloro-4-fluoro-5-hydrazino-phenoxyacetate.

Next, formulation examples are shown. In addition, a compound is shown by the compound number as described in the above (Table 25). Parts are parts by weight.
Formulation Example 1
50 parts of each of compounds 5-1 to 5-9, 3 parts of calcium lignin sulfonate, 2 parts of sodium lauryl sulfate and 45 parts of synthetic silicon hydroxide are thoroughly pulverized and mixed to obtain each wettable powder.
Formulation Example 2
10 parts of each of compounds 5-1 to 5-9, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate, 35 parts of xylene and 35 parts of cyclohexanone are mixed well to obtain each emulsion.
Formulation Example 3
2 parts of each of the compounds 5-1 to 5-9, 2 parts of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 64 parts of kaolin clay, and kneaded well after adding water, Granulate and dry to obtain each granule.
Formulation Example 4
25 parts of each of compounds 5-1 to 5-9, 50 parts of a 10% aqueous solution of polyvinyl alcohol and 25 parts of water are mixed, and each suspension is wet-pulverized until the average particle size is 5 micrometers or less. Get the agent.

Next, test examples show that the pyridazin-3-one derivative represented by the general formula 10 is useful as an active ingredient of a herbicide.
The evaluation of herbicidal efficacy and phytotoxicity is “0” when the budding or growing state of the test plants (weeds and crops) at the time of the survey is no or almost different from that of the untreated plants. A case where complete death or budding or growth is completely suppressed is classified as “5”, and is divided into 6 stages of 0 to 5 and indicated by 0, 1, 2, 3, 4, and 5. Evaluations of herbicidal efficacy “4” and “5” mean excellent herbicidal efficacy, and ratings “3” and below mean insufficient herbicidal efficacy.

Test Example 1 Upland field foliage treatment test A cylindrical plastic pot having a diameter of 10 cm and a depth of 10 cm was stuffed with soil, seeded with malva american morning glory, and green grass and grown in a greenhouse for 19 days. Thereafter, the test compound is made into an emulsion according to Formulation Example 2, and a predetermined amount thereof is diluted with water containing a spreading agent equivalent to 1000 liters per hectare, and is uniformly applied from above the plant body to the entire foliage with a sprayer. Processed. After the treatment, the plants were grown in a greenhouse for 19 days and examined for herbicidal efficacy. The results are shown in (Table 26).

Test Example 2 Upland soil surface treatment test A cylindrical plastic pot having a diameter of 10 cm and a depth of 10 cm was filled with soil, and Malba american morning glory and lobster were sown. The test compound was made into an emulsion according to Formulation Example 2, and a predetermined amount thereof was diluted with water equivalent to 1000 liters per hectare and uniformly treated on the entire soil surface with a sprayer. After the treatment, it was grown in a greenhouse on 19th and examined for herbicidal efficacy. The results are shown in (Table 27).

Test Example 3 Paddy paddy treatment test A cylindrical plastic pot with a diameter of 9 cm and a depth of 11 cm was filled with soil, and Tainubie was sown. After flooding and making a paddy field, it was grown in a greenhouse. Seven days later, the test compound was made into an emulsion according to Formulation Example 2, a predetermined amount thereof was diluted with water, and 50 liters per hectare were treated on the water surface. The plants were grown in a greenhouse for 19 days after the treatment and examined for herbicidal efficacy. The results are shown in (Table 28).

Claims (7)

General formula

Wherein, R ² represents a hydrogen atom or a C1-C3 alkyl group, R ³ represents a hydrogen atom, Q is the formula of 2

[Wherein, X represents a C androgenic atom, Y represents a halogen atom,
B represents an OR ¹ group .
{Wherein R ¹ represents a hydrogen atom, a C1-C6 alkyl group , a C3 -C6 alkynyl group, or a ( C1-8 alkoxy) carbonyl C1-6 alkyl group . }]
Q- 1 represented by Or a salt thereof. The carboxylic acid derivative or a salt thereof according to claim 1, wherein X is a fluorine atom, and Y is a chlorine atom. R ¹ The carboxylic acid derivative or a salt thereof according to claim 1 or 2, wherein is a hydrogen atom, isopropyl group, 1-methyl-2-propynyl group or (ethoxycarbonyl) methyl group. R ² Is a hydrogen atom, a methyl group or an ethyl group, The carboxylic acid derivative or salt thereof according to any one of claims 1 to 3. The carboxylic acid derivative according to any one of claims 1 to 4. Salt is alkali metal salt, alkaline earth metal salt, methylamine salt, dimethylamine salt, trimethylamine salt, ethylamine salt, diethylamine salt, triethylamine salt, diisopropylethylamine salt, tri-n-propylamine salt, tri-n-butylamine salt The carboxylic acid derivative salt according to claim 1, which is pyridine salt, 4-dimethylaminopyridine salt, N, N-dimethylaniline salt or N, N-diethylaniline salt. The salt of a carboxylic acid derivative according to claim 6, wherein the salt is a triethylamine salt.