[go: up one dir, main page]

WO2004026839A1 - Procede pour produire un compose d'arylethynylpyrazole - Google Patents

Procede pour produire un compose d'arylethynylpyrazole Download PDF

Info

Publication number
WO2004026839A1
WO2004026839A1 PCT/JP2003/012012 JP0312012W WO2004026839A1 WO 2004026839 A1 WO2004026839 A1 WO 2004026839A1 JP 0312012 W JP0312012 W JP 0312012W WO 2004026839 A1 WO2004026839 A1 WO 2004026839A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
producing
arylethynyl
virazoles
halogenated
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2003/012012
Other languages
English (en)
Japanese (ja)
Inventor
Takao Urata
Naoko Sumitani
Liangyou He
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Agro Kanesho Co Ltd
Original Assignee
Agro Kanesho Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Agro Kanesho Co Ltd filed Critical Agro Kanesho Co Ltd
Priority to AU2003266548A priority Critical patent/AU2003266548A1/en
Publication of WO2004026839A1 publication Critical patent/WO2004026839A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

Definitions

  • the present invention relates to a method for producing an acetylene derivative useful as a medicinal and agricultural chemical, and more particularly, to a method for producing an arylethirubirazole useful as an agricultural chemical.
  • Halogen compounds in particular coupling reaction of aromatic halides with acetylenes, it is known to be carried out in the presence of a catalytic component of a copper halide phosphine ligand ZCuI such as Pd compound / PPh 3 This is generally called the Sonogashira reaction.
  • This reaction is known to be applicable not only to aromatic halogen compounds but also to heterocyclic aromatic halogen compounds.
  • the coupling reaction between pyrazols and acetylenes is carried out by palladium acetate, PPh 3 .
  • PPh 3 palladium acetate
  • the reaction proceeds in the presence of a catalyst component in combination with Cul and a base (see Japanese Patent Publication No. 2001-158704 (pages 8 and 13-14)).
  • a catalyst component in combination with Cul and a base
  • heteroaromatic halogenated compounds 2-phenylindole and methyl propyl It has been reported that Cu I and PP h 3 are used as catalyst components in the force-coupling reaction with carbon nanotubes (JCS, Perkin Trans. 1, (1999), p.2669-2670).
  • An object of the present invention is to provide a production method for industrially advantageously reacting a halogenated virazole and an arylacetylene in a power coupling reaction.
  • the present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have found that copper coupling and copper halide can be performed without using an expensive Pd compound in the coupling reaction between halogenated virazoles and aryl acetylenes.
  • the present inventors have found that by performing a reaction in the presence of a base, the coupling reaction proceeds under mild conditions, and thus completed the present invention.
  • the gist of the present invention is characterized in that, when a halogenated pyrazole is reacted with an arylacetylene to produce an arylethyrivazole, the reaction is carried out in the presence of a copper halide and a base.
  • the production method of the present invention is characterized in that a reaction catalyst comprising a copper halide and a base is used in producing an aryl ethynyl virazole by reacting a halogenated pyrazole with an aryl acetylene. Is what you do. (Halogenated pyrazoles)
  • the halogen atom may be substituted at any of the 3-, 4- and 5-positions of the pyrazole ring, and a substituent other than the halogen atom is bonded to the pyrazole ⁇ . May be.
  • the halogenated pyrazoles it is preferable to use a 2- (5-pyrazolyl) acetic acid ester derivative represented by the general formula (1).
  • R 1 is a hydrogen atom; a fluorine atom, a chlorine atom, a bromine atom, a halogen atom such as an iodine atom; a methyl group, a chloromethyl group, a bromomethyl group, a odomethyl group, a fluoromethyl group, a difluoromethinole group Trifluoromethyl, 2,2,2-trifluoroethyl, ethyl, methoxymethyl, t-butyl, perfluorobutyl, perfluorooctyl, acetylmethyl, etc.
  • alkyl group which may be substituted with an active group
  • an alkenyl group which may be substituted with a group which is inert to the reaction, such as a vinyl group, an aryl group, a 2-butenyl group, and a styryl group
  • an ethynyl group —Phenylethynyl group, 2— (p-chlorophenyl) ethynyl group
  • Alkynyl group which may be substituted with a group which is inactive in this reaction such as 2, 2-trimethylsilylethynyl group; a group which is inactive in this reaction such as methoxy group, ethoxy group, benzyloxy group and 2-methoxyethoxy group
  • R 1 is a methyl group, an ethyl group, a chloromethyl group, a bromomethyl group, a chloromethyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group,
  • An alkyl group having 1 to 4 carbon atoms such as a perfluorobutyl group or a haloalkyl group is preferred, a haloalkyl group is more preferred, and a trifluoromethyl group is particularly preferred.
  • R 2 represents a hydrogen atom, an alkyl group, a haloalkyl group, or an optionally substituted aryl group.
  • alkyl group examples include an alkyl group having 1 to 20 carbon atoms such as a methyl group, an ethyl group, an isopropyl group, a t-butyl group, a cyclohexyl group, an octyl group and a decyl group.
  • Haloalkyl groups include trifluoromethyl, chloromethyl, dichloromethyl, and perfluorobutyl, etc. Examples are -20 haloalkyl groups.
  • aryl group which may be substituted examples include phenyl, naphthyl, 4-trifluoromethylphenyl, o-tolyl, 4-nitrophenyl, 3-cyanophenyl, 3, 6 Examples thereof include aryl groups having 6 to 20 carbon atoms, such as —di-t-butyl naphthyl group.
  • R 2 is preferably a hydrogen atom, an alkyl group or a haloalkyl group, more preferably a hydrogen atom or an alkyl group, particularly, a methyl group, an ethyl group, and a butyl group.
  • R 3 is an alkyl group such as a methyl group, an ethyl group, an isopropyl group, a t-butyl group, a cyclohexyl group, an octyl group, and a decyl group; an aralkyl group such as a penzyl group and a phenyl group; or a phenyl group and a naphthyl group And an aryl group such as a group.
  • the alkyl group preferably has 1 to 20 carbon atoms
  • the aralkyl group preferably has 7 to 20 carbon atoms
  • the aralkyl group preferably has 6 to 12 carbon atoms.
  • an alkyl group having 1 to 4 carbon atoms such as a methyl group, an ethyl group and a t-butyl group, a benzyl group or a phenyl group is preferable, and a methyl group or an ethyl group is particularly preferable.
  • X represents a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, of which a bromine atom or an iodine atom is preferable, and an iodine atom is particularly preferable.
  • the 2- (5-pyrazolyl) acetic acid ester derivative represented by the general formula (1) can be synthesized, for example, according to the synthesis method described in Japanese Patent Application Laid-Open No. 2001-158704. it can.
  • arylacetylenes of the present invention include phenylacetylene, substituted phenylacetylene, and naphthylacetylene. Of these, a phenylacetylene derivative represented by the following general formula (2), which is a substituted phenylacetylene, is preferable.
  • R 4 is a halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom; an alkyl such as a methyl group, an ethyl group, an isopropyl group, a t-butyl group, a cyclohexyl group, a heptyl group, an octyl group, and a cyclooctyl group.
  • halogen atom such as a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom
  • an alkyl such as a methyl group, an ethyl group, an isopropyl group, a t-butyl group, a cyclohexyl group, a heptyl group, an octyl group, and a cyclooctyl group.
  • Haloalkyl groups such as chloromethyl group, difluoromethyl group, trifluoromethyl group, 2-bromocyclopropyl group, perfluorobutyl group, perfluorooctyl group, 5-pentyl iodide group; methoxy group; Alkoxy groups such as ethoxy group, propoxy group, butoxy group and octoxy group; haloalkoxy groups such as chloromethoxy group, cycloethoxy group, trifluoroethoxy group and the like; alkylthio groups such as methylthio group, ethylthio group and t-butylthio group Group; or trifluoromethylthio group, trifluoroethylthio group, A haloalkylthio group such as a propylthio group.
  • alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio and haloalkylthio groups preferably have 1 to 8 carbon atoms.
  • R 4 is preferably a halogen atom, a haloalkyl group or a haloalkoxy group, more preferably a halogen atom or a haloalkyl group having 1 to 4 carbon atoms, particularly a fluorine atom or a trifluoromethyl group. Is preferred.
  • n an integer of 0 to 5, preferably 1 or 2.
  • the phenylacetylene derivative represented by the general formula (2) is described in, for example, J. Org. Chem. 50, 1763 (1985) cited in Japanese Patent Application Laid-Open No. 2001-157870. Was done It can be synthesized according to the synthesis method.
  • the amount of aryl acetylenes used is usually
  • Copper halide used as a catalyst may be a monovalent copper halide such as cuprous fluoride, cuprous chloride, cuprous bromide, cuprous iodide, cupric chloride, cupric bromide, etc.
  • Examples thereof include divalent copper halides such as copper and cupric iodide.
  • monovalent copper halide is preferred, and cuprous chloride, cuprous bromide or cuprous iodide is preferred to suppress the dimerization reaction of the acetylene compound itself, and iodide is preferred.
  • Copper (I) is particularly preferred.
  • the amount of the copper halide to be used is not particularly limited.However, from the viewpoint of economy and simplicity of the treatment after the reaction, the amount is preferably less than 1 equivalent, preferably 0. It is used in an amount of not more than 8 equivalents, more preferably not more than 0.5 equivalent. Although the lower limit depends on the reactivity, it is usually at least 0.1 equivalent, preferably at least 0.1 equivalent.
  • copper nodogenide acts as a catalyst, the reaction can be carried out by adding an additive that does not affect the reaction and that forms a complex. Examples of the additive include a nitrogen-containing ligand such as 2,2′-biviridyl and an ammonium salt such as n-butylammonium bromide. (base)
  • This reaction is performed in the presence of a base.
  • the base include inorganic substances such as sodium hydroxide, sodium hydroxide, calcium hydroxide, barium hydroxide, sodium carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, cesium carbonate, and potassium phosphate.
  • Bases; or amines such as triethylamine, pyridine and piperidine can be used.
  • inorganic bases are preferred from the viewpoint of economy, and more preferred are carbonates such as cesium carbonate, potassium carbonate and sodium hydrogen carbonate.
  • the amount of the base used is 1 equivalent or more based on the halogenated pyrazole.
  • the amount used is determined in terms of economy and reactivity, but can be selected up to 10 equivalents. It can be selected preferably within a range of 5 equivalents or less, more preferably 3 equivalents or less.
  • This reaction may be carried out without a solvent when the substrate is a liquid, but a solvent is usually used.
  • the solvent used in this reaction is not particularly limited as long as it is inert to the reaction, but preferably has a boiling point of 80 ° C. or higher.
  • aprotic polar solvents such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, DMI, HMPA, DMS0, and sulfolane; or hydrocarbon solvents such as heptane, toluene, and xylene Etc. are exemplified. Of these, preferred are polar solvents containing an amide group such as dimethylformamide, dimethylacetamide, and N-methyl-2-pyrrolidone.
  • the amount of the solvent used is 1 to 100 times, preferably 2 to 100 times, more preferably 5 to 20 times, by volume / weight ratio to the substrate.
  • the reaction temperature needs to be 80 ° C. or higher for the reaction to substantially proceed. It is preferably in the range of 90 ° C, more preferably in the range of 100 ° C to 120 ° C.
  • the reaction can be performed in air, but is preferably performed in an atmosphere of an inert gas such as nitrogen or argon to suppress the dimerization reaction of the acetylene compound.
  • the reaction method is as follows:
  • aryl acetylenes can react with copper and copper iodide to form copper acetylide, and then react with pyrogenic and pyrogenated pyrogens. From the above, it is preferable to use the above method (1) or (2), which is a method in which aryl acetylenes and copper halide are mixed in advance.
  • the reaction time is not particularly limited, but is usually 1 hour to 36 hours, preferably 1 to 24 hours.
  • the reaction can be carried out by a usual post-treatment method.
  • the reaction solution can be washed with an aqueous solution of ammonium chloride and removed to the aqueous layer as a copper-amine complex.
  • extraction and washing operations are performed, and the desired product can be isolated by crystallization, distillation, and column purification. In some cases, it can be used in the next step without isolation.
  • the effluent was diluted with 5 OmL of gelatin, washed twice with 15 mL of saturated saline, and dried over anhydrous magnesium sulfate.
  • the solution obtained by removing magnesium sulfate by filtration was concentrated, and 6.55 g of 3,5-bistrifluoromethylphenylacetylene was obtained as a clear colorless solution. Isolation yield 81.5%. 92.6% purity (HP LC internal standard method).
  • degassed DMF in 2.5 mL was 3,4-bistrifluoromethylphenylacetylene 144 mg (0.604 mmol), followed by n-butylammonium bromide 55 mg (0.173 mmol) and copper iodide 0) 33 mg (0.173 mmol).
  • 88 mg (0.623 mmol) of carbon dioxide lime and 200 mg (0.575 mmol) of methyl 1-methyl-4-oxide-3-trifluoromethylpyrazole-5-ylacetate were added, and the reaction was performed.
  • the solution was kept at 100 ° C and stirred for 7 hours.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

Cette invention se rapporte à un procédé dans lequel la réaction de couplage d'un composé de pyrazole halogéné avec un composé d'arylacéthylène est facilement réalisée au moyen d'un réactif peu coûteux, tout en produisant un rendement satisfaisant. Ce procédé, qui sert à produire un composé d'aryléthynylpyrazole par la réaction d'un composé de pyrazole halogéné avec un composé d'arylacéthylène, se caractérise en ce que la réaction est réalisée en présence d'un halogénure de cuivre et d'une base.
PCT/JP2003/012012 2002-09-19 2003-09-19 Procede pour produire un compose d'arylethynylpyrazole Ceased WO2004026839A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003266548A AU2003266548A1 (en) 2002-09-19 2003-09-19 Process for producing arylethynylpyrazole compound

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2002/272480 2002-09-19
JP2002272480A JP2004107264A (ja) 2002-09-19 2002-09-19 アリールエチニルピラゾール類の製造方法

Publications (1)

Publication Number Publication Date
WO2004026839A1 true WO2004026839A1 (fr) 2004-04-01

Family

ID=32024932

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2003/012012 Ceased WO2004026839A1 (fr) 2002-09-19 2003-09-19 Procede pour produire un compose d'arylethynylpyrazole

Country Status (3)

Country Link
JP (1) JP2004107264A (fr)
AU (1) AU2003266548A1 (fr)
WO (1) WO2004026839A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8329703B2 (en) 2005-02-15 2012-12-11 Xtl Biopharmaceuticals Ltd. Pyrazole compounds

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0648723A1 (fr) * 1993-10-13 1995-04-19 Sumitomo Chemical Company Limited Composé diphényle acétylénique, procédé pour sa préparation, composition et élément de cristal liquide le contenant
WO1999046247A1 (fr) * 1998-03-11 1999-09-16 Mitsubishi Chemical Corporation Composes a base de pyrazole et produits chimiques agricoles renfermant ces composes en tant que principe actif
WO2001020993A1 (fr) * 1999-09-24 2001-03-29 Agro-Kanesho Co., Ltd. Agents insecticides et acaricides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0648723A1 (fr) * 1993-10-13 1995-04-19 Sumitomo Chemical Company Limited Composé diphényle acétylénique, procédé pour sa préparation, composition et élément de cristal liquide le contenant
WO1999046247A1 (fr) * 1998-03-11 1999-09-16 Mitsubishi Chemical Corporation Composes a base de pyrazole et produits chimiques agricoles renfermant ces composes en tant que principe actif
WO2001020993A1 (fr) * 1999-09-24 2001-03-29 Agro-Kanesho Co., Ltd. Agents insecticides et acaricides

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8329703B2 (en) 2005-02-15 2012-12-11 Xtl Biopharmaceuticals Ltd. Pyrazole compounds

Also Published As

Publication number Publication date
JP2004107264A (ja) 2004-04-08
AU2003266548A1 (en) 2004-04-08

Similar Documents

Publication Publication Date Title
CN106061972B (zh) 5-氟-4-亚氨基-3-(烷基/取代烷基)-1-(芳基磺酰基)-3,4-二氢嘧啶-2(1h)-酮及其制备方法
JP4731503B2 (ja) 複素環式化合物のスルフィニル化方法
KR20180100114A (ko) 4-((6-(2-(2,4-디플루오로페닐)-1,1-디플루오로-2-히드록시-3-(1h-1,2,4-트리아졸-1-일)프로필)피리딘-3-일)옥시)벤조니트릴 및 제조방법
KR20180101342A (ko) 4-((6-(2-(2,4-디플루오로페닐)-1,1-디플루오로-2-히드록시-3-(1h-1,2,4-트리아졸-1-일)프로필)피리딘-3-일)옥시)벤조니트릴 및 제조방법
WO2023214552A1 (fr) Composition d'agent de sulfonylation de trifluorométhane et procédé de production d'un composé trifluorométhanesulfonyloxy ou d'un composé trifluorométhane sulfonyle
CN117550960A (zh) 用于制备1-(3,5-二氯-4-氟-苯基)-2,2,2-三氟-乙酮的方法
JP5512551B2 (ja) 置換ビフェニルアニリド類を調製する方法
JP6256484B2 (ja) ピリダジン化合物の製造方法
WO2004026839A1 (fr) Procede pour produire un compose d'arylethynylpyrazole
JP7582997B2 (ja) 殺有害生物化合物の調製方法
CN102639483A (zh) 芳香族二氟乙酸酯的制造方法
JP2009102264A (ja) アセチル誘導体の製造方法
KR102246226B1 (ko) 로잘탄 대사체 exp-3174의 제조방법
JP3880883B2 (ja) ピリジン誘導体、その製造方法、及び除草剤中間体としての用途
KR20190002519A (ko) 제초성 피리디닐이미다졸론 화합물의 제조 방법
JP2896949B2 (ja) １−（４−アシルフェニル）アゾール類の製造方法
JP4211081B2 (ja) ４−シアノピリダジン−３−オン誘導体
JP3787821B2 (ja) ベンズアミドキシム化合物の製造方法
JP5205971B2 (ja) テトラヒドロピラン化合物の製造方法
KR20030085788A (ko) 피리딘 유도체, 그의 제조방법, 및 제초제 중간체로서의용도
JP4194984B2 (ja) フェニルナフチルイミダゾール化合物
KR100539725B1 (ko) 피롤의 새로운 알킬화 반응
US6956132B2 (en) Process for producing 2-phenylacetophenone derivatives and precursors therefor
JPH02101064A (ja) ピラゾールカルボン酸アミド類の製造方法
JPH1135563A (ja) アゾール−１−イルアルキルニトリル類の製造法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase