JP2002530382A - Method for producing 5-amino-3- (thio) carbamoylpyrazole - Google Patents
Method for producing 5-amino-3- (thio) carbamoylpyrazoleInfo
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- JP2002530382A JP2002530382A JP2000583871A JP2000583871A JP2002530382A JP 2002530382 A JP2002530382 A JP 2002530382A JP 2000583871 A JP2000583871 A JP 2000583871A JP 2000583871 A JP2000583871 A JP 2000583871A JP 2002530382 A JP2002530382 A JP 2002530382A
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- 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
- C07D231/14—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
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- 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
- C07D231/14—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
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Abstract
(57)【要約】 本発明は５−アミノ−３−（チオ）カルバモイルピラゾールの新規な製造法に関する。 (57) [Summary] The present invention relates to a novel method for producing 5-amino-3- (thio) carbamoylpyrazole.
Description
【０００１】 本発明は５−アミノ−３−（チオ）カルバモイルピラゾールの新規な製造法に
関する。The present invention relates to a novel method for producing 5-amino-3- (thio) carbamoylpyrazole.
【０００２】 式（Ｂ１）Formula (B1)
【０００３】[0003]
【化６】 Embedded image
【０００４】 （式中、Ｅ＝エステル基である） のピラゾール誘導体を通常の方法で最初に式（Ｃ１） Ｃｌ−Ｓ（Ｏ）m−Ｚ （Ｃ１） の塩化物と反応させ、得られる誘導体を、次いで、例えばアンモニアを用いて、
エステル基においてアミド化すると、式（Ａ１）A pyrazole derivative of the formula (where E = ester group) is first reacted in a conventional manner with a chloride of the formula (C1) Cl—S (O) m —Z (C1), the derivative obtained And then using, for example, ammonia,
When amidated at the ester group, the compound represented by the formula (A1)
【０００５】[0005]
【化７】 Embedded image
【０００６】 （式中、Ａｒ＝場合により置換されていることができるフェニル又はピリジルで
あり；Ｚ＝特にハロゲノアルキルであり、ｍ＝０、１又は２である） の５−アミノ−３−カルバモイルピラゾールが得られることは既知である（例え
ばＥＰ ０ ５００ ２０９参照）。Wherein Ar = phenyl or pyridyl, which may be optionally substituted; Z = especially halogenoalkyl, m = 0, 1 or 2, 5-amino-3-carbamoyl It is known that pyrazoles are obtained (see, for example, EP 0 500 209).
【０００７】 式（Ｂ２）Formula (B2)
【０００８】[0008]
【化８】 Embedded image
【０００９】 のピラゾール誘導体を通常の方法で最初に式（Ｃ１）の塩化物と反応させ、得ら
れる誘導体を次いで硫化水素を用いてシアノ基において誘導体化すると、式（Ａ
２）The pyrazole derivative of the formula (I) is first reacted in a conventional manner with the chloride of the formula (C1) and the resulting derivative is then derivatized at the cyano group with hydrogen sulfide to give the formula (A
2)
【００１０】[0010]
【化９】 Embedded image
【００１１】 （式中、Ａｒ＝場合により置換されていることができるフェニル又はピリジルで
あり；Ｚ＝特にハロゲノアルキルであり、ｍ＝０、１又は２である） の５−アミノ−３−チオカルバモイルピラゾールが得られることも既知である（
例えば、ＤＥ−Ａ １ ９６ ５０ １９７、ＷＯ ９８／２８ ２７９参照）。Wherein Ar = phenyl or pyridyl, which may be optionally substituted; Z = particularly halogenoalkyl, m = 0, 1 or 2 It is also known that carbamoylpyrazole can be obtained (
For example, see DE-A 196 50 197, WO 98/28 279).
【００１２】 しかしながら、両方法は、完成されたピラゾール環系から出発して２段階の反
応順が必要であるという欠点を有する。さらに、硫化水素の使用は毒性的に安心
できない試薬を用いることを意味する。[0012] However, both methods have the disadvantage that a two-step reaction sequence is required starting from the completed pyrazole ring system. Furthermore, the use of hydrogen sulfide means the use of toxic unreliable reagents.
【００１３】 今回、式（ＩＩ）This time, the formula (II)
【００１４】[0014]
【化１０】 Embedded image
【００１５】 ［式中、 ＡはＮ又は基Ｃ−Ｈａｌ’を示し、ここで Ｈａｌ’はハロゲンを示し、 Ｈａｌはハロゲンを示し、 Ｘは酸素又は硫黄を示す］ のピラゾール誘導体を式（ＩＩＩ） Ｈａｌ”−Ｙ−Ｒ （ＩＩＩ） ［式中、 Ｈａｌ”はハロゲン、特に塩素又は臭素を示し、 Ｒはハロゲノアルキル又はアルキルを示し、 ＹはＳ、ＳＯ又はＳＯ2を示す］ のハロゲン化物と、適宜希釈剤の存在下に且つ適宜反応剤の存在下で反応させ、
そして適宜、 ａ）得られる式（Ｉａ）（Ｘ＝Ｏ）Wherein A represents N or a group C-Hal ′, wherein Hal ′ represents a halogen, Hal represents a halogen, and X represents oxygen or sulfur. A pyrazole derivative of the formula (III) Hal "-Y-R (III) [ wherein, Hal" is halogen, in particular shows a chlorine or bromine, R represents indicates halogenoalkyl or alkyl, Y is S, shows the SO or SO 2] and a halide of, Reacting appropriately in the presence of a diluent and optionally in the presence of a reactant,
And optionally, a) the resulting formula (Ia) (X = O)
【００１６】[0016]
【化１１】 Embedded image
【００１７】 ［式中、 Ａ、Ｈａｌ、Ｙ及びＲは上記で定義した通りである］ の化合物を、続いて、適宜希釈剤の存在下で硫化剤と反応させるか； あるいは ｂ）得られる式（Ｉｂ）（Ｙ＝Ｓ）Wherein A, Hal, Y and R are as defined above, are then reacted with a sulfurizing agent, optionally in the presence of a diluent; or b) the resulting formula (Ib) (Y = S)
【００１８】[0018]
【化１２】 Embedded image
【００１９】 ［式中、 Ａ、Ｈａｌ、Ｘ及びＲは上記で定義した通りである］ の化合物を、続いて、適宜希釈剤の存在下に且つ適宜触媒の存在下で酸化剤を用
いて酸化する ことにより、式（Ｉ）Wherein A, Hal, X and R are as defined above, followed by oxidation with an oxidizing agent, optionally in the presence of a diluent and optionally in the presence of a catalyst. By doing so, the formula (I)
【００２０】[0020]
【化１３】 Embedded image
【００２１】 ［式中、 Ａ、Ｈａｌ、Ｘ、Ｙ及びＲは上記で定義した通りである］ の５−アミノ−３−（チオ）カルバモイルピラゾールが簡単な方法で得られるこ
とが見いだされた。Wherein A, Hal, X, Y and R are as defined above, have been found to be obtained in a simple manner.
【００２２】 式（Ｉ）は、本発明に従って製造され得る５−アミノ−３−（チオ）カルバモ
イルピラゾールの一般的定義を与える。上記及び下記に言及する式中に挙げられ
ている好ましい置換基あるいは基の範囲を以下に示す。 Ａは好ましくはＮ又は基Ｃ−Ｈａｌ’を示し、ここで Ｈａｌ’はフッ素又は塩素を示す。 Ｈａｌは好ましくはフッ素又は塩素を示す。 Ｘは好ましくは酸素又は硫黄を示す。 Ｙは好ましくはＳ、ＳＯ又はＳＯ2を示す。 Ｒは好ましくはフッ素、塩素及び臭素より成る群からの１〜９個の同一もしくは
異なるハロゲン原子を有する（Ｃ1−Ｃ4）−ハロゲノアルキルを示すか、あるい
は（Ｃ1−Ｃ4）−アルキルを示す。 Ｒは特に好ましくは基：−ＣＦ3、−ＣＨＦ2、−ＣＦ2ＣＨ3、−ＣＦ2ＣＨＦ2、
−ＣＦ2ＣＨＦＣｌ、−ＣＨ2ＣＦ3、−ＣＨ2−ＣＦ2Ｃｌ、−ＣＨ2−ＣＦ2ＣＨ
Ｆ2、−ＣＦ2−ＣＦＣｌ−ＣＦ3、−Ｃ（Ｃｌ）（ＣＦ3）−ＣＦ2Ｃｌ、−Ｃ（
Ｃｌ）（ＣＦ3）−ＣＨＣｌ−ＣＦ3、ならびにまた−ＣＨ3及び−Ｃ2Ｈ5の１つ
を示す。Formula (I) provides a general definition of 5-amino-3- (thio) carbamoylpyrazole that can be prepared according to the present invention. Preferred ranges of the substituents or groups mentioned in the formulas mentioned above and below are shown below. A preferably denotes N or the group C-Hal ', wherein Hal' denotes fluorine or chlorine. Hal preferably represents fluorine or chlorine. X preferably represents oxygen or sulfur. Y preferably represents S, SO or SO 2. R preferably represents (C 1 -C 4 ) -halogenoalkyl having 1 to 9 identical or different halogen atoms from the group consisting of fluorine, chlorine and bromine, or represents (C 1 -C 4 ) -alkyl Is shown. R is particularly preferably a group: -CF 3, -CHF 2, -CF 2 CH 3, -CF 2 CHF 2,
-CF 2 CHFCl, -CH 2 CF 3 , -CH 2 -CF 2 Cl, -CH 2 -CF 2 CH
F 2, -CF 2 -CFCl-CF 3, -C (Cl) (CF 3) -CF 2 Cl, -C (
Cl) (CF 3) -CHCl- CF 3, and also shows one of -CH 3 and -C 2 H 5.
【００２３】 本発明に従う方法は、式（ＩＡ）又は（ＩＢ）The process according to the invention can be carried out according to formula (IA) or (IB)
【００２４】[0024]
【化１４】 Embedded image
【００２５】 ［式中、 Ａ、Ｈａｌ及びＲは上記で定義した通りである］ の化合物、ならびに ＡがＣ−Ｃｌを示し、 ＨａｌがＣｌを示し、 Ｒが−ＣＦ3を示す 化合物の製造に最も好適に用いられる。Wherein A, Hal and R are as defined above, and a compound wherein A represents C—Cl, Hal represents Cl, and R represents —CF 3 Most preferably used.
【００２６】 驚くべきことに、本発明に従う式（ＩＩ）のピラゾール誘導体と式（ＩＩＩ）
のハロゲン化物の反応において、式（Ｉ）の化合物が高い選択性を以て得られ−
予想されるＨ2Ｎ−ＣＯ（Ｓ）基におけるハロゲン化物の競争反応は観察されな
い（このことに関し、例えば、Ｌｉｅｂｉｇｓ Ａｎｎ．７２７（１９６９），
２２；Ｊ．Ｏｒｇ．Ｃｈｅｍ．ＵＳＳＲ（Ｅｎｇｌ．ｔｒａｎｓ．）１９６７，
９６３；Ｊ．Ｃｈｅｍ．Ｓｏｃ．１９５３，５４９；Ｔｅｔｒａｈｅｄｒｏｎ ５０ （１９９４），５０８３及びＵＳ ２４ ７６ ６５５を参照されたい）。Surprisingly, the pyrazole derivatives of the formula (II) according to the invention and the formula (III)
The compound of formula (I) is obtained with high selectivity in the reaction of the halide of
Expected HTwoNo competing reactions of halides at the N-CO (S) group were observed.
(In this regard, see, for example, Liebigs Ann.727(1969),
22; Org. Chem. USSR (Engl.trans.)1967,
963; Chem. Soc.1953, 549; Tetrahedron 50 (1994), 5083 and US Pat. No. 2,476,655).
【００２７】 本発明に従う反応は、完成されたピラゾール環系から出発して簡単な１−段階
反応で本発明に従う化合物を得ることができるという利点を有する。さらに、チ
オアミド誘導体の製造は硫化水素を必要としない。The reaction according to the invention has the advantage that starting from the completed pyrazole ring system, the compounds according to the invention can be obtained in a simple one-step reaction. Furthermore, the production of thioamide derivatives does not require hydrogen sulfide.
【００２８】 例えば、５−アミノ−３−カルバモイル−１−（２，６−ジクロロ−４−トリ
フルオロメチルフェニル）ピラゾール及び塩化トリフルオロメチルスルフィニル
を出発材料として用い、次いで硫化剤として五硫化リンを用いると、本発明に従
う方法及び引き続いて行われる変法（ａ）の反応の経路は下記のスキームにより
示すことができる：For example, 5-amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole and trifluoromethylsulfinyl chloride are used as starting materials, followed by phosphorus pentasulfide as sulfurizing agent. When used, the route of the reaction of the process according to the invention and of the subsequent variant (a) can be illustrated by the following scheme:
【００２９】[0029]
【化１５】 Embedded image
【００３０】引き続き行われる変法（ａ） Subsequent variant (a)
【００３１】[0031]
【化１６】 Embedded image
【００３２】 本発明に従う方法で出発材料として用いられるべきピラゾール誘導体のいくつ
かは既知であり（例えば、ＤＥ １ ９６ ５０ １９７及びＥＰ ０ ５００
２０９参照）、及び／又は一般的に既知の方法でそれらを得ることができる。Some of the pyrazole derivatives to be used as starting materials in the process according to the invention are known (eg DE 196 50 197 and EP 0 500
209) and / or they can be obtained in a generally known manner.
【００３３】 式（ＩＩａ）Formula (IIa)
【００３４】[0034]
【化１７】 Embedded image
【００３５】 ［式中、 Ｈａｌ及びＨａｌ’は上記で定義した通りである］ のピラゾール誘導体は従来未知であり、本出願の主題の一部でもある。Wherein the Hal and Hal 'are as defined above, are previously unknown and are also part of the subject matter of the present application.
【００３６】 式（ＩＩａ）のピラゾール誘導体は、対応する３−シアノピラゾール誘導体を
既知の方法でシアノ基において誘導体化することにより得られる（例えば、ＥＰ
０ ２９５ １１７又は製造実施例を参照されたい）。The pyrazole derivative of the formula (IIa) is obtained by derivatizing the corresponding 3-cyanopyrazole derivative at a cyano group in a known manner (for example EP
0 295 117 or the production examples).
【００３７】 本発明に従う方法で出発材料としてやはり用いられるべき式（ＩＩＩ）のハロ
ゲン化物は、有機化学の一般的に既知の化合物である。The halides of the formula (III) which are also to be used as starting materials in the process according to the invention are generally known compounds of organic chemistry.
【００３８】 本発明に従う方法を行うために適した希釈剤は不活性有機溶媒である。これら
には、特に、脂肪族、脂環式又は芳香族の、場合によりハロゲン化されているこ
とができる炭化水素、例えばベンジン、ベンゼン、トルエン、キシレン、クロロ
ベンゼン、石油エーテル、ヘキサン、シクロヘキサン、ジクロロメタン、クロロ
ホルム、四塩化炭素；エーテル類、例えばジエチルエーテル、ジオキサン、テト
ラヒドロフラン又はエチレングリコールジメチルエーテルもしくはエチレングリ
コールジエチルエーテル、ケトン類、例えばアセトン又はブタノン、ニトリル類
、例えばアセトニトリル又はプロピオニトリル；アミド類、例えばジメチルホル
ムアミド、ジメチルアセトアミド、Ｎ−メチルホルムアニリド、Ｎ−メチルピロ
リドン又はヘキサメチルリン酸トリアミド、エステル類、例えば酢酸エチル、ス
ルホキシド類、例えばジメチルスルホキシドあるいは酸、例えば酢酸が含まれる
。[0038] Suitable diluents for carrying out the process according to the invention are inert organic solvents. These include, in particular, aliphatic, cycloaliphatic or aromatic, optionally halogenated hydrocarbons such as benzene, benzene, toluene, xylene, chlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, Chloroform, carbon tetrachloride; ethers such as diethyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl ether or ethylene glycol diethyl ether, ketones such as acetone or butanone, nitriles such as acetonitrile or propionitrile; amides such as dimethylformamide , Dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide, esters such as ethyl acetate, sulfoxides Such as dimethyl sulfoxide or acids include, for example, acetic acid.
【００３９】 適宜、本発明に従う方法を反応助剤の存在下で行うことができる。適した反応
助剤は通常の無機もしくは有機塩基、さらに第１級、第２級もしくは第３級アミ
ン類の塩酸塩、トシレート及びメシレート、ならびにまた塩酸である。If appropriate, the process according to the invention can be carried out in the presence of a reaction aid. Suitable reaction auxiliaries are the customary inorganic or organic bases, as well as the hydrochlorides of primary, secondary or tertiary amines, tosylate and mesylate, and also hydrochloric acid.
【００４０】 本発明に従う方法を行う場合、反応温度は比較的広い範囲内で変化することが
できる。一般に反応は−２０℃〜＋１２０℃の温度、好ましくは０℃〜＋５０℃
の温度で行われる。When carrying out the process according to the invention, the reaction temperatures can be varied within a relatively wide range. Generally, the reaction is carried out at a temperature between -20C and + 120C, preferably between 0C and + 50C.
At a temperature of
【００４１】 本発明に従う方法を行うために、式（ＩＩ）のピラゾール誘導体のモル当たり
一般に１．０〜２．５モル、好ましくは１．０〜１．５モルの式（ＩＩＩ）のハ
ロゲン化物及び適宜１．０〜２．５モル、好ましくは１．０〜１．５モルの反応
助剤が用いられる。反応及び仕上げの実施ならびに反応生成物の単離は、一般的
に通常の方法により行われる。To carry out the process according to the invention, generally 1.0 to 2.5 mol, preferably 1.0 to 1.5 mol, of the halide of the formula (III) per mole of the pyrazole derivative of the formula (II) And 1.0 to 2.5 mol, preferably 1.0 to 1.5 mol of a reaction assistant is used as appropriate. The reaction and work-up and the isolation of the reaction products are generally carried out by customary methods.
【００４２】 本発明に従う引き続き行われる変法（ａ）を行うために適した希釈剤は、好ま
しくは不活性有機溶媒、特に炭化水素、例えばトルエン、キシレン、テトラリン
、ヘキサン又はシクロヘキサンあるいはエーテル類、例えばテトラヒドロフラン
である。Suitable diluents for carrying out the subsequent variant (a) according to the invention are preferably inert organic solvents, in particular hydrocarbons such as toluene, xylene, tetralin, hexane or cyclohexane or ethers, such as It is tetrahydrofuran.
【００４３】 本発明に従う引き続き行われる変法（ａ）を行う場合、反応温度は比較的広い
範囲内で変化することができる。一般に反応は０℃〜２００℃、好ましくは２０
℃〜１５０℃の温度で行われる。When carrying out the subsequent variant (a) according to the invention, the reaction temperatures can be varied within a relatively wide range. Generally, the reaction is carried out at 0 ° C to 200 ° C, preferably at 20 ° C.
It is carried out at a temperature of between 150C and 150C.
【００４４】 本発明に従う引き続き行われる変法（ａ）を行う場合、式（Ｉａ）の化合物の
モル当たり一般に１〜３モル、好ましくは１〜２モルの硫化剤が用いられる。仕
上げは通常の方法により行われる。In carrying out the subsequent variant (a) according to the invention, generally 1 to 3 mol, preferably 1 to 2 mol, of sulfurizing agent are used per mole of compound of formula (Ia). Finishing is performed by a usual method.
【００４５】 本発明に従う引き続き行われる変法（ｂ）を行うために適した酸化剤は、硫黄
の酸化のために通常用いられるすべての酸化剤である。特に適しているのは過酸
化水素、有機過酸、例えば過酢酸、ｍ−クロロ過安息香酸、ｐ−ニトロ過安息香
酸又は大気酸素である。Oxidants suitable for carrying out the subsequent variant (b) according to the invention are all oxidants usually used for the oxidation of sulfur. Particularly suitable are hydrogen peroxide, organic peracids such as peracetic acid, m-chloroperbenzoic acid, p-nitroperbenzoic acid or atmospheric oxygen.
【００４６】 本発明に従う引き続き行われる変法（ｂ）を行うために適した希釈剤は同様に
不活性有機溶媒である。炭化水素、例えばベンジン、ベンゼン、トルエン、キシ
レン又は石油エーテル；塩素化炭化水素、例えばジクロロメタン、１，２−ジク
ロロエタン、クロロホルム、四塩化炭素又はクロロベンゼン；エーテル類、例え
ばジエチルエーテル、ジオキサン又はテトラヒドロフラン；カルボン酸、例えば
酢酸又はプロピオン酸、あるいは双極性非プロトン性溶媒、例えばアセトニトリ
ル、アセトン、酢酸エチル又はジメチルホルムアミドを用いるのが好ましい。Suitable diluents for carrying out the subsequent variant (b) according to the invention are likewise inert organic solvents. Hydrocarbons such as benzine, benzene, toluene, xylene or petroleum ether; chlorinated hydrocarbons such as dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride or chlorobenzene; ethers such as diethyl ether, dioxane or tetrahydrofuran; It is preferred to use, for example, acetic acid or propionic acid, or a dipolar aprotic solvent, such as acetonitrile, acetone, ethyl acetate or dimethylformamide.
【００４７】 本発明に従う引き続き行われる変法（ｂ）は、適宜、酸結合剤の存在下で行わ
れ得る。適した酸結合剤は、通常用いられ得るすべての有機及び無機酸結合剤で
ある。アルカリ土類金属もしくはアルカリ金属水酸化物、酢酸塩もしくは炭酸塩
、例えば水酸化カルシウム、水酸化ナトリウム、酢酸ナトリウム又は炭酸ナトリ
ウムを用いるのが好ましい。The subsequent variant (b) according to the invention can optionally be carried out in the presence of an acid binder. Suitable acid binders are all commonly used organic and inorganic acid binders. It is preferred to use an alkaline earth metal or alkali metal hydroxide, acetate or carbonate, for example calcium hydroxide, sodium hydroxide, sodium acetate or sodium carbonate.
【００４８】 本発明に従う引き続き行われる変法（ｂ）は、適宜、適した触媒の存在下で行
われ得る。適した触媒は、そのような硫黄の酸化のために通常用いられるすべて
の金属塩触媒である。これに関し、モリブデン酸アンモニウム及びタングステン
酸ナトリウムを例として挙げることができる。The subsequent variant (b) according to the invention can, if appropriate, be carried out in the presence of a suitable catalyst. Suitable catalysts are all metal salt catalysts normally used for such sulfur oxidation. In this connection, mention may be made of ammonium molybdate and sodium tungstate as examples.
【００４９】 本発明に従う引き続き行われる変法（ｂ）を行う場合、反応温度は比較的広い
範囲内で変化することができる。一般に反応は−２０℃〜＋７０℃の温度、好ま
しくは０℃〜＋５０℃の温度で行われる。When carrying out the subsequent variant (b) according to the invention, the reaction temperatures can be varied within a relatively wide range. Generally, the reaction is carried out at a temperature between -20C and + 70C, preferably between 0C and + 50C.
【００５０】 本発明に従う引き続き行われる変法（ｂ）を行う場合、硫黄の酸化をスルホキ
シド段階で中断させるべき場合には、式（Ｉｂ）の化合物のモル当たり一般に０
．８〜１．２モル、好ましくは等モル量の酸化剤が用いられる。スルホンへの酸
化のためには、式（Ｉｂ）の化合物のモル当たり一般に１．８〜３．０モル、好
ましくは２倍モル量の酸化剤が用いられる。反応及び仕上げの実施ならびに最終
的生成物の単離は通常の方法により行われる。When carrying out the subsequent variant (b) according to the invention, if the oxidation of the sulfur is to be interrupted in the sulfoxide stage, it is generally 0% per mole of compound of the formula (Ib)
. The oxidizing agent is used in an amount of 8 to 1.2 mol, preferably equimolar. For the oxidation to the sulphone, generally 1.8 to 3.0 mol, preferably twice the molar amount of oxidizing agent are used per mol of the compound of the formula (Ib). The reaction and work-up are carried out and the final product is isolated according to customary methods.
【００５１】 本発明に従う方法により製造されるべき式（Ｉ）の５−アミノ−３−（チオ）
カルバモイルピラゾールは生物学的に活性な化合物、例えば殺虫剤（ｉｎｓｅｃ
ｔｉｃｉｄｅｓ）である（例えば、ＤＥ １ ９６ ５０ １９７及びＷＯ ９
８／２８ ２７９参照）。The 5-amino-3- (thio) of formula (I) to be prepared by the process according to the invention
Carbamoylpyrazoles are biologically active compounds, such as insecticides (insec
ticides) (for example, DE 196 50 197 and WO 9).
8/28 279).
【００５２】[0052]
【実施例】製造実施例 実施例１ EXAMPLES Preparation Example Example 1
【００５３】[0053]
【化１８】 Embedded image
【００５４】 トルエン（６ｍｌ）中の５−アミノ−３−カルバモイル−１−（２，６−ジク
ロロ−４−トリフルオロメチルフェニル）ピラゾール（１．０ｇ、３．０ミリモ
ル）［実施例（ＩＩ−１）］及びピリジニウム−ｐ−トルエンスルホネート（１
．１ｇ、４．５ミリモル）を塩化トリフルオロメチルスルフィニル（０．６ｇ、
３．９ミリモル）と混合する。反応混合物を５０℃で１８時間加熱し、次いで冷
却し、水（２０ｍｌ）を加え、混合物を酢酸エチルで十分に抽出する。合わせた
有機抽出物をＮａ2ＣＯ3（水溶液）及び水で洗浄し、次いでシリカゲル／活性炭
／ＭｇＳＯ4と混合し、濾過する。濾液を完全に濃縮し、残留物を減圧下で乾燥
し、５−アミノ−３−カルバモイル−１−（２，６−ジクロロ−４−トリフルオ
ロメチルフェニル）−４−トリフルオロメチルスルフィニルピラゾール（１．２
ｇ、ＧＣ：９３．２％、理論値の８１．９％）を淡いベージュ色の固体として得
る。出発材料の製造 5-Amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole (1.0 g, 3.0 mmol) in toluene (6 ml) [Example (II- 1)] and pyridinium-p-toluenesulfonate (1
. 1 g, 4.5 mmol) in trifluoromethylsulfinyl chloride (0.6 g,
3.9 mmol). The reaction mixture is heated at 50 ° C. for 18 hours, then cooled, water (20 ml) is added and the mixture is thoroughly extracted with ethyl acetate. The combined organic extracts are washed with Na 2 CO 3 (aq) and water, then mixed with silica gel / activated carbon / MgSO 4 and filtered. The filtrate was completely concentrated, the residue was dried under reduced pressure and 5-amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole (1 .2
g, GC: 93.2%, 81.9% of theory) as a pale beige solid. Production of starting materials
【００５５】[0055]
【化１９】 Embedded image
【００５６】 ５−アミノ−３−シアノ−１−（２，６−ジクロロ−４−トリフルオロメチル
フェニル）ピラゾール（６．４ｇ、０．０２モル）をジオキサン（１４５ｍｌ）
／水（１２０ｍｌ）中に溶解する。Ｋ2ＣＯ3（１２．０ｇ、０．０９モル）を加
え、混合物を次いで０℃において３０％−Ｈ2Ｏ2（２７．５ｍｌ、０．２７モル
）と、滴下により混合し、室温で２時間撹拌し、反応溶液を水（５００ｍｌ）中
に注ぎ、酢酸エチルで繰り返し抽出する。合わせた有機抽出物をＮａ2ＨＳＯ3（
水溶液）で洗浄し、Ｎａ2ＳＯ4上で乾燥し、溶媒を蒸留し、残留物を減圧下で乾
燥する。5-Amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole (6.4 g, 0.02 mol) was added to dioxane (145 ml).
/ Dissolve in water (120 ml). K 2 CO 3 (12.0 g, 0.09 mol) was added and the mixture was then mixed dropwise at 0 ° C. with 30% -H 2 O 2 (27.5 ml, 0.27 mol) at room temperature. Stir for an hour, pour the reaction solution into water (500 ml) and extract repeatedly with ethyl acetate. The combined organic extracts were combined with Na 2 HSO 3 (
Aqueous solution), dry over Na 2 SO 4 , distill off the solvent and dry the residue under reduced pressure.
【００５７】 これは５−アミノ−３−カルバモイル−１−（２，６−ジクロロ−４−トリフ
ルオロメチルフェニル）ピラゾール（５．６ｇ、ＨＰＬＣ：９８．３％、理論値
の８１．２％）を黄色の固体として与える。実施例２ This is 5-amino-3-carbamoyl-1- (2,6-dichloro-4-trifluoromethylphenyl) pyrazole (5.6 g, HPLC: 98.3%, 81.2% of theory). As a yellow solid. Example 2
【００５８】[0058]
【化２０】 Embedded image
【００５９】 Ｐ4Ｓ10（０．３８ｇ、０．８５ミリモル）及びＮａ2ＣＯ3（０．０９ｇ、０
．８５ミリモル）をＴＨＦ（２０ｍｌ）中に懸濁させ、混合物を室温で、黄色の
溶液が生成するまで（約３０分）撹拌する。５−アミノ−３−カルバモイル−１
−（２，６−ジクロロ−４−トリフルオロメチルフェニル）−４−トリフルオロ
メチルスルフィニルピラゾール（０．３ｇ、０．６５ミリモル）［実施例１］を
加え、反応混合物を室温で２４時間撹拌し、水中に注ぎ、酢酸エチルで抽出し、
有機抽出物をＮａＨＣＯ3（飽和）で洗浄し、Ｎａ2ＳＯ4上で乾燥し、溶媒を蒸
留により除去した後に５−アミノ−１−（２，６−ジクロロ−４−トリフルオロ
メチルフェニル）−３−チオカルバモイル−４−（トリフルオロメチルスルフィ
ニル）ピラソールを得る。P 4 S 10 (0.38 g, 0.85 mmol) and Na 2 CO 3 (0.09 g, 0
. (85 mmol) are suspended in THF (20 ml) and the mixture is stirred at room temperature until a yellow solution forms (about 30 minutes). 5-amino-3-carbamoyl-1
-(2,6-Dichloro-4-trifluoromethylphenyl) -4-trifluoromethylsulfinylpyrazole (0.3 g, 0.65 mmol) [Example 1] is added and the reaction mixture is stirred at room temperature for 24 hours. , Poured into water, extracted with ethyl acetate,
The organic extract is washed with NaHCO 3 (sat.), Dried over Na 2 SO 4 and, after removal of the solvent by distillation, 5-amino-1- (2,6-dichloro-4-trifluoromethylphenyl)- 3-thiocarbamoyl-4- (trifluoromethylsulfinyl) pyrazole is obtained.
───────────────────────────────────────────────────── フロントページの続き (81)指定国 ＥＰ(ＡＴ，ＢＥ，ＣＨ，ＣＹ， ＤＥ，ＤＫ，ＥＳ，ＦＩ，ＦＲ，ＧＢ，ＧＲ，ＩＥ，Ｉ Ｔ，ＬＵ，ＭＣ，ＮＬ，ＰＴ，ＳＥ)，ＯＡ(ＢＦ，ＢＪ ，ＣＦ，ＣＧ，ＣＩ，ＣＭ，ＧＡ，ＧＮ，ＧＷ，ＭＬ， ＭＲ，ＮＥ，ＳＮ，ＴＤ，ＴＧ)，ＡＰ(ＧＨ，ＧＭ，Ｋ Ｅ，ＬＳ，ＭＷ，ＳＤ，ＳＬ，ＳＺ，ＴＺ，ＵＧ，ＺＷ )，ＥＡ(ＡＭ，ＡＺ，ＢＹ，ＫＧ，ＫＺ，ＭＤ，ＲＵ， ＴＪ，ＴＭ)，ＡＥ，ＡＬ，ＡＭ，ＡＴ，ＡＵ，ＡＺ， ＢＡ，ＢＢ，ＢＧ，ＢＲ，ＢＹ，ＣＡ，ＣＨ，ＣＮ，Ｃ Ｒ，ＣＵ，ＣＺ，ＤＥ，ＤＫ，ＤＭ，ＥＥ，ＥＳ，ＦＩ ，ＧＢ，ＧＤ，ＧＥ，ＧＨ，ＧＭ，ＨＲ，ＨＵ，ＩＤ， ＩＬ，ＩＮ，ＩＳ，ＪＰ，ＫＥ，ＫＧ，ＫＰ，ＫＲ，Ｋ Ｚ，ＬＣ，ＬＫ，ＬＲ，ＬＳ，ＬＴ，ＬＵ，ＬＶ，ＭＡ ，ＭＤ，ＭＧ，ＭＫ，ＭＮ，ＭＷ，ＭＸ，ＮＯ，ＮＺ， ＰＬ，ＰＴ，ＲＯ，ＲＵ，ＳＤ，ＳＥ，ＳＧ，ＳＩ，Ｓ Ｋ，ＳＬ，ＴＪ，ＴＭ，ＴＲ，ＴＴ，ＴＺ，ＵＡ，ＵＧ ，ＵＳ，ＵＺ，ＶＮ，ＹＵ，ＺＡ，ＺＷ (71)出願人 Ｄ−51368 Ｌｅｖｅｒｋｕｓｅｎ，Ｇｅ ｒｍａｎｙ──────────────────────────────────────────────────続 き Continuation of front page (81) Designated country EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, IT, LU, MC, NL, PT, SE ), OA (BF, BJ, CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, KE, LS, MW, SD, SL, SZ, TZ, UG, ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, CH, CN, CR, CU, CZ, DE, DK, DM, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID , IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, NO, NZ, PL, PT, RO, RU, SD, SE, SG, SI, SK, SL, TJ, TM, TR, TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW (71 ) Applicant D-51368 Leverkusen, Germany
Claims (6)
ことを特徴とする式（Ｉ） 【化２】 ［式中、 Ａ、Ｈａｌ、Ｘ、Ｙ及びＲは上記で定義した通りである］ の５−アミノ−３−（チオ）カルバモイルピラゾールの製造法。1. A compound of the formula (II) Wherein A represents N or a group C-Hal ′, wherein Hal ′ represents a halogen, Hal represents a halogen, X represents oxygen or sulfur. Y-R (III) [wherein, Hal "is halogen, in particular shows a chlorine or bromine, R represents indicates halogenoalkyl or alkyl, Y represents S, SO or SO 2] and a halide of, as appropriate diluent Wherein the reaction is carried out in the presence of and optionally a reactant. [Wherein A, Hal, X, Y and R are as defined above], for producing a 5-amino-3- (thio) carbamoylpyrazole.
する請求項１に記載の方法。2. Formula (Ia) (X = O) Wherein A, Hal, Y and R are as defined in claim 1), followed by reacting with a sulfurizing agent, optionally in the presence of a diluent. The method described in.
いて酸化することを特徴とする請求項１に記載の方法。3. Formula (Ib) (Y = S) Wherein A, Hal, X and R are as defined in claim 1), followed by oxidation with an oxidizing agent, optionally in the presence of a diluent and optionally in the presence of a catalyst. The method of claim 1, wherein:
ゲン原子を有する（Ｃ1−Ｃ4）−ハロゲノアルキルを示すか、あるいは（Ｃ1−
Ｃ4）−アルキルを示す ことを特徴とする請求項１〜３の１つに記載の方法。4. A represents N or a group C-Hal ′, wherein Hal ′ represents fluorine or chlorine, Hal represents fluorine or chlorine, and R represents 1 to 4 from the group consisting of fluorine, chlorine and bromine. Represents (C 1 -C 4 ) -halogenoalkyl having 9 identical or different halogen atoms, or (C 1-
4. The process according to claim 1, wherein C 4 ) -alkyl is present.
ＣＦ2ＣＨＦ2、−ＣＦ2−ＣＦＣｌ−ＣＦ3、−Ｃ（Ｃｌ）（ＣＦ3）−ＣＦ2Ｃｌ
、−Ｃ（Ｃｌ）（ＣＦ3）−ＣＨＣｌ−ＣＦ3、−ＣＨ3、−Ｃ2Ｈ5の１つを示す
ことを特徴とする請求項１〜４のいずれかに記載の方法。5. R is the following group: —CFThree, -CHFTwo, -CFTwoCHThree, -CF Two CHFTwo, -CFTwoCHFCl, -CHTwoCFThree, -CHTwo-CFTwoCl, -CHTwo−
CFTwoCHFTwo, -CFTwo-CFCl-CFThree, -C (Cl) (CFThree) -CFTwoCl
, -C (Cl) (CFThree) -CHCl-CFThree, -CHThree, -CTwoHFiveShow one of
A method according to any of claims 1 to 4, characterized in that:
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19853560A DE19853560A1 (en) | 1998-11-20 | 1998-11-20 | Single-stage preparation of 4-substituted pyrazole compounds useful e.g. as insecticides, from new or known 4-unsubstituted compound and halide |
| DE19853560.0 | 1998-11-20 | ||
| PCT/EP1999/008642 WO2000031043A2 (en) | 1998-11-20 | 1999-11-10 | Method for producing 5-amino-3-(thio)carbamoylpyrazoles |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002530382A true JP2002530382A (en) | 2002-09-17 |
Family
ID=7888443
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000583871A Pending JP2002530382A (en) | 1998-11-20 | 1999-11-10 | Method for producing 5-amino-3- (thio) carbamoylpyrazole |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1131300A2 (en) |
| JP (1) | JP2002530382A (en) |
| KR (1) | KR20010085955A (en) |
| CN (1) | CN1326446A (en) |
| AU (1) | AU1270400A (en) |
| DE (1) | DE19853560A1 (en) |
| HK (1) | HK1041002A1 (en) |
| IL (1) | IL142643A0 (en) |
| WO (1) | WO2000031043A2 (en) |
| ZA (1) | ZA200103144B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007504184A (en) * | 2003-09-04 | 2007-03-01 | バイエル・クロツプサイエンス・エス・アー | Insecticide |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7262214B2 (en) | 2003-02-26 | 2007-08-28 | Merial Limited | 1-N-arylpyrazole derivatives in prevention of arthropod-borne and mosquito-borne diseases |
| AU2007316718B2 (en) | 2006-11-10 | 2013-03-28 | Basf Se | Process for the sulfinylation of a pyrazole derivative |
| ES2398595T3 (en) | 2006-11-10 | 2013-03-20 | Basf Se | Procedure for sulfinylation of a pyrazole derivative |
| DE102006061537A1 (en) | 2006-12-27 | 2008-07-03 | Bayer Healthcare Ag | Agent for controlling parasites on animals comprises an N-phenylpyrazole, an aliphatic cyclic carbonate and an aliphatic polyether |
| DE102006061538A1 (en) | 2006-12-27 | 2008-07-03 | Bayer Healthcare Ag | Agent for controlling parasites on animals comprises an N-phenylpyrazole, a pyrethroid, an aliphatic cyclic carbonate and an aliphatic polyether |
| EA019071B1 (en) | 2008-10-02 | 2013-12-30 | Мериал Лимитед | Method for producing and purifying trifluoromethanesulfinic acid |
| WO2013000572A1 (en) | 2011-06-30 | 2013-01-03 | 2LUTION GmbH | Composition for controlling parasites on animals |
| JO3626B1 (en) | 2012-02-23 | 2020-08-27 | Merial Inc | Topical compositions comprising fipronil and permethrin and methods of use |
| WO2020188376A1 (en) * | 2019-03-19 | 2020-09-24 | Gharda Chemicals Limited | A process for synthesis of fipronil |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO179282C (en) * | 1991-01-18 | 1996-09-11 | Rhone Poulenc Agrochimie | New 1- (2-pyridyl) pyrazole compounds for control of insect pests |
| DE19650197A1 (en) * | 1996-12-04 | 1998-06-10 | Bayer Ag | 3-thiocarbamoylpyrazole derivatives |
| EA003995B1 (en) * | 1996-12-24 | 2003-12-25 | Рон-Пуленк Агро | Pesticidal 1-aryl and pyridylpyrazole derivatives |
-
1998
- 1998-11-20 DE DE19853560A patent/DE19853560A1/en not_active Withdrawn
-
1999
- 1999-11-10 KR KR1020017005158A patent/KR20010085955A/en not_active Application Discontinuation
- 1999-11-10 IL IL14264399A patent/IL142643A0/en unknown
- 1999-11-10 AU AU12704/00A patent/AU1270400A/en not_active Abandoned
- 1999-11-10 JP JP2000583871A patent/JP2002530382A/en active Pending
- 1999-11-10 EP EP99955971A patent/EP1131300A2/en not_active Withdrawn
- 1999-11-10 CN CN99813520A patent/CN1326446A/en active Pending
- 1999-11-10 WO PCT/EP1999/008642 patent/WO2000031043A2/en not_active Application Discontinuation
-
2001
- 2001-04-18 ZA ZA2001/03144A patent/ZA200103144B/en unknown
-
2002
- 2002-04-18 HK HK02102935.2A patent/HK1041002A1/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007504184A (en) * | 2003-09-04 | 2007-03-01 | バイエル・クロツプサイエンス・エス・アー | Insecticide |
Also Published As
| Publication number | Publication date |
|---|---|
| DE19853560A1 (en) | 2000-05-25 |
| EP1131300A2 (en) | 2001-09-12 |
| HK1041002A1 (en) | 2002-06-28 |
| ZA200103144B (en) | 2002-06-26 |
| WO2000031043A2 (en) | 2000-06-02 |
| IL142643A0 (en) | 2002-03-10 |
| CN1326446A (en) | 2001-12-12 |
| KR20010085955A (en) | 2001-09-07 |
| AU1270400A (en) | 2000-06-13 |
| WO2000031043A3 (en) | 2000-11-09 |
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