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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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
- C07D231/14—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
-
- 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
-
- 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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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 |
CA2667562A1 (en) | 2006-11-10 | 2008-05-15 | Basf Se | Process for the sulfinylation of a pyrazole derivative |
CA2667559A1 (en) | 2006-11-10 | 2008-05-15 | Basf Se | Process for the sulfinylation of a pyrazole derivative |
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 |
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 |
EP2349987B1 (en) | 2008-10-02 | 2012-11-14 | Basf Se | Method for producing and purifying trifluoromethanesulfinic acid |
BR112013033914A2 (en) | 2011-06-30 | 2016-11-22 | Hansen Ab Gmbh | agent for the control of parasites in animals and use of an agent |
JO3626B1 (en) | 2012-02-23 | 2020-08-27 | Merial Inc | Topical compositions comprising fipronil and permethrin and methods of use |
EP3941907A4 (en) * | 2019-03-19 | 2023-01-04 | 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 |
CA2275634A1 (en) * | 1996-12-24 | 1998-07-02 | Rhone-Poulenc Agrochimie | Pesticidal 1-aryl and pyridylpyrazole derivatives |
-
1998
- 1998-11-20 DE DE19853560A patent/DE19853560A1/en not_active Withdrawn
-
1999
- 1999-11-10 JP JP2000583871A patent/JP2002530382A/en active Pending
- 1999-11-10 IL IL14264399A patent/IL142643A0/en unknown
- 1999-11-10 KR KR1020017005158A patent/KR20010085955A/en not_active Application Discontinuation
- 1999-11-10 CN CN99813520A patent/CN1326446A/en active Pending
- 1999-11-10 AU AU12704/00A patent/AU1270400A/en not_active Abandoned
- 1999-11-10 WO PCT/EP1999/008642 patent/WO2000031043A2/en not_active Application Discontinuation
- 1999-11-10 EP EP99955971A patent/EP1131300A2/en not_active Withdrawn
-
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 |
---|---|
EP1131300A2 (en) | 2001-09-12 |
CN1326446A (en) | 2001-12-12 |
ZA200103144B (en) | 2002-06-26 |
HK1041002A1 (en) | 2002-06-28 |
IL142643A0 (en) | 2002-03-10 |
WO2000031043A2 (en) | 2000-06-02 |
WO2000031043A3 (en) | 2000-11-09 |
KR20010085955A (en) | 2001-09-07 |
AU1270400A (en) | 2000-06-13 |
DE19853560A1 (en) | 2000-05-25 |
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