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WO1996026188A1 - 2-chloropyridines et procede de fabrication des produits de depart associes - Google Patents

2-chloropyridines et procede de fabrication des produits de depart associes Download PDF

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Publication number
WO1996026188A1
WO1996026188A1 PCT/JP1996/000383 JP9600383W WO9626188A1 WO 1996026188 A1 WO1996026188 A1 WO 1996026188A1 JP 9600383 W JP9600383 W JP 9600383W WO 9626188 A1 WO9626188 A1 WO 9626188A1
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WIPO (PCT)
Prior art keywords
group
formula
represented
methyl
pyridine
Prior art date
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Ceased
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PCT/JP1996/000383
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English (en)
Japanese (ja)
Inventor
Shiro Terashima
Tadashi Kato
Tsuyoshi Kajiyashiki
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Sagami Chemical Research Institute
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Sagami Chemical Research Institute
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/61—Halogen atoms or nitro radicals

Definitions

  • the present invention relates to a method for producing 2-chloro-monochloromethylpyridines, 2-chlorodichloromethylpyridines and 2-chloro-trichloromethylpyridines, which is useful as a raw material for producing pharmaceuticals and agricultural chemicals, and a raw material for producing the same. And a method for producing methyl-2-sulfonylpyridines.
  • a common method for producing 2-chloro-monochloromethylpyridines, 2-chlorodichloromethylpyridines, and 2-chloro-trichloromethylpyridines useful as intermediates in the production of pharmaceuticals and pesticides is methyl-
  • a method obtained by chlorination of 2-chloro pyridines [DE-3630046 (EP-A-0260485), JP-A-5-230024, EP-A-0557967] is known.
  • the starting material, methyl-2-chloropyridine is obtained by oxidizing methylpyridine by the method described in Tetrahedron Letters (1972, p. 2807). Obtained by chlorination according to the method described in Chemistry of Heterocyclic Compounds, Vol.
  • 2-chloro-monochloromethylpyridines 2-chlorodichloromethylpyridines
  • 2-chlorotrichloromethylpyridines are methylpyridines. It is manufactured through three more steps, and the total yield is low when the entire process is performed.
  • wastewater treatment of oxine chloride used for chlorination of methylpyridine N-oxide is essential for environmental protection.
  • 2-Chloromonochloromethylpyridines, 2-chlorodichloromethylpyridines, and 2-chlorotrichloromethylpyridines have also been produced by direct chlorination of methylpyridine [USP-5247093 (WO94 / 13640), USP-4577027, USP-4564681].
  • the reaction requires a high temperature of 300 to 500 and its low yield makes it unsuitable for industrial production.
  • 2-chloro-5-chloromethylpyridine a method for preparing 2-chloro-5-methylpyridine by chlorination [DE-3630 046 (EP-A-0260485), DE-4016175, EP-A-0557967 And Japanese Patent Application Laid-Open No. Hei 5 230026 are known.
  • This raw material, 2-chloro-5-methylpyridine is produced via the corresponding methylpyridine N-oxide as described above.
  • 3-dichloromethylpyridine obtained by chlorination of 3-methylpyridine is converted into 2-methoxy-5-methoxymethylpyridine, and further added to oxychlorine or to it.
  • the present inventors have industrially prepared 2-chloro-monochloromethylpyridines, 2-chlorodichloromethylpyridines, 2-chloro-trichloromethylpyridines, and methyl-2-sulfonylpyridines, which are raw materials for producing the same.
  • Various studies were conducted to provide a process that can be manufactured easily and inexpensively.
  • chlorinated ⁇ was allowed to act on methyl-2-sulfonylpyridines under radical generating conditions, 2-methyl-monochloromethylpyridine was obtained.
  • 2-sulfonylpyridines as raw materials for production can be produced at once and selectively from sulfonylcyanide and methyl-substituted 1-acyloxy 1,3-butadiene. They have found that they can be manufactured easily and easily, and have completed the present invention. That is, the present invention provides the following general formula (I)
  • R 1 represents a lower alkyl group, a cycloalkyl group, a substituted or unsubstituted aryl group, or an aralkyl group.
  • the CH 3 group may be any of the 3- to 6-positions of 2-sulfonylpyridines.
  • a chlorinating agent is allowed to act on methyl-2-sulfonylpyridine represented by) under radical generating conditions, wherein the following formula ( ⁇ ) is used.
  • Methyl-2-sulfonylpyridines represented by the above general formula (I) are produced by reacting with 1,3-butadiene, and the resulting methyl-2-sulfonylpyridines (I) are added with chlorine under radical generating conditions.
  • 2-chlorodichloromethylpyridines represented by the above formula (m) 2-chlorodichloromethylpyridines represented by the above formula (m), and / or
  • the present invention relates to a method for producing 2-chloro-trichloromethylpyridines represented by the above formula (IV).
  • the present invention is characterized in that a sulfonyl cyanide represented by the general formula (V) is reacted with a methyl-substituted 1-acyloxy-1,3-butadiene represented by the general formula (VI).
  • the present invention relates to a method for producing a methyl-2-sulfonylpyridine represented by the general formula (I).
  • the lower alkyl group includes a methyl group, an ethyl group, a propyl group, and the like
  • the cycloalkyl group includes a cyclopentyl group, a cyclohexyl group, a cyclooctyl group, and the like.
  • the aryl group include a phenyl group and a naphthyl group. These include a lower alkyl group such as a methyl group and an ethyl group, a lower alkoxy group such as a methoxy group and a propoxy group, a fluorine atom, a chlorine atom, and a bromine atom. And may be appropriately replaced by a halogen atom, a cyano group, a nitro group, or the like.
  • the aralkyl group include a benzyl group and a phenyl group.
  • the CH 3 group means that it is present at any of the 3- to 6-positions of 2-sulfonylpyridines, and a CH 2 C1 group, CHC1 2 groups and 3 CC1 groups are the 3-position of 2-pyridine Means that it is in any of the 6th positions.
  • the chlorinating agent any one can be used as long as it generates a chlorine radical under radical generating conditions, but chlorine or sulfuryl chloride is preferred in terms of reaction efficiency and cost.
  • the chlorinating agent is preferably added continuously or sequentially during the reaction.
  • a radical initiator can be used.
  • radical initiators include nitriles such as 2,2'-azobis (isobutyronitrile) and 1,1'-azobis (cyclohexanecarbonitrile), and peroxides such as benzoyl peroxide and acetyl chloride. Things.
  • the radical initiator can be added before or during the reaction or continuously or sequentially during the reaction. The added amount of the radical initiator is from 0.001 to 3.0 equivalents, preferably from 0.05 to 1.0 equivalent.
  • a chlorine radical can be generated by light irradiation or the like.
  • This reaction is preferably performed in a solvent, and any solvent may be used as long as it does not participate in the reaction.
  • the solvent include acetate nitrile, carbon disulfide, tetrachloroethane, carbon tetrachloride, and the like. And a mixed solvent of carbon tetrachloride and chloroform.
  • the reaction is preferably carried out at a temperature from 20 ° C. to the reflux temperature of the solvent, more preferably from 60 ° C. to 100 ° C.
  • 2-chloro-monochloromethylpyridines ⁇
  • 2-chloro-chlorochloromethylpyridines (1 ⁇ )
  • 2-chloro-trichloromethylpyridines IV
  • acyloxy group examples include an acetoxy group, a propanoloxy group, a butanoloxy group, and a benzoyloxy group.
  • the starting sulfonylcyanide (V) can be obtained from the corresponding sodium sulfinate by the method described in Organic Synthesis (Vol. 57, p. 88, 1977).
  • the other starting material, methyl-substituted 1-hydroxyl-1,3-butadiene (VI), is, for example, Industrial and Engineering Chemistry, Vol. 41, No. 12, p. 2920, 1949. Year) can be obtained in the manner described.
  • sulfonyl cyanide (V) used for the reaction include lower alkane sulfonyl cyanide such as methane sulfonyl cyanide, propane sulfonyl cyanide, cyclohexane sulfonyl cyanide, cyclohexane sulfonyl cyanide, cyclooctane sulfonyl cyanide Arylalkanesulfonyls such as cycloalkanesulfonyl cyanide, benzenesulfonylcyanide, p-toluenesulfonylcyanide, p-chlorobenzenesulfonylcyanide, etc. Cyanide.
  • lower alkane sulfonyl cyanide such as methane sulfonyl cyanide, propane sulfonyl cyanide, cyclohexane sulfon
  • methyl-substituted 1,3-butadiene (VI) to be subjected to the reaction include 4-acetoxy 1,3-pentene, 4-propanoyloxy 1,3-pentene, 1-acetoxy-isoprene, and 1-1.
  • the sulfonyl cyanide represented by the above general formula (V) and the above general formula (VD The reaction with a methyl-substituted 1-acyloxy-1,3-butadiene represented by the formula (1) can be carried out under Diels-Alder reaction conditions, and is carried out in the presence or absence of a polymerization inhibitor. In this reaction, it is considered that once the Diels-Alder adduct is formed, the elimination reaction proceeds under the reaction conditions to obtain the target compound represented by the general formula (I).
  • polymerization inhibitor examples include phenols such as 4-methoxyphenol, 2,6-di-tert-butyl-1-methylphenol, hydroquinones such as hydroquinone and di-tert-butylhydroquinone, and 1-naphthane.
  • phenols such as 4-methoxyphenol, 2,6-di-tert-butyl-1-methylphenol, hydroquinones such as hydroquinone and di-tert-butylhydroquinone, and 1-naphthane.
  • naphthols such as tol and 2-naphthol
  • catechols such as potassium and p-tert-butyl catechol.
  • the amount of the polymerization inhibitor to be added is preferably 1 / 100,000 to 1/100 of the weight of gen, more preferably 1/10000 to 1/1000.
  • a solvent can be used. Any solvent can be used as long as it does not participate in the reaction.
  • solvents include hydrocarbons such as hexane and octane, halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane, getyl ether, and tetrahydroquinone.
  • examples include ethers such as drofuran and aromatic hydrocarbons such as toluene and xylene.
  • reaction is preferably carried out between 20 ° C and 120 ° C, more preferably between 60 ° C and 100 ° C.
  • methyl-2-sulfonyl pyridines corresponding to the methyl-substituted position on the methyl-substituted 1-acyloxy-1,3-butadiene represented by the general formula (VI) are obtained. . That is, 4-Asiloxy 1,3—Penyu Gen 6-Methyl-2 —Sulfonylpyridine, 1-Acyoxy-isoprene, 5—Methyl—2-sulfonylpyridine, 1-Acyoxy—3-methyl-1,3—Butadiene, 4-methyl-2-sulfonylpyridine, Acyloxy 1,3-pentadiene gives 3-methyl-2-sulfonylpyridine.
  • Example 1 4-methyl-2-phenylsulfonylpyridine having the following physical property values was obtained by using 1-acetoxy 3-methyl-1,3-butadiene in place of 11-acetoxysoprene to obtain a white solid (yield: 85.0%).
  • Example 1 4-acetoxy-1,3-pentadiene was used in place of 11-acetoxysoprene to obtain 6-methyl-2-phenylsulfonylpyridine having the following physical properties, which was converted to a yellow semi-solid (yield: 25.8). %).
  • 2,2'-azobis isobutyl nitrile (10mg, 0.061 ⁇ 1) and 5-methyl-2-phenylsulfonyl pyridine (290mg, 0.125 ol) were added to acetate nitrile (20g) at room temperature. Is suspended, and chlorine (0.3 ml / s) is added to the reaction mixture under heating and refluxing while adding 2,2'-azobis (isobutyronitrile) (2.5 nig, 0.015 mraol) every 15 minutes. Minutes. Under heating and refluxing, nitrogen was blown into the reaction solution for 3 minutes, and a saturated aqueous solution of sodium hydrogen carbonate (30 ml) was added to make the solution viscous.
  • 5-methyl-2-sulfonylpyridine (2.33 g, 10.O mmol octylsulfuryl chloride (1.8 ml, 22.4 ol) and ⁇ , ⁇ '-azobis (isobutyronitrile) were added to carbon tetrachloride (30 ml) at room temperature. (120 mg, 0.7 mmol) were suspended, and 1.5 hours after the start of reflux, ⁇ , bisazobis (isobutyronitrile: 120 mg, 0.7 mmol). Also, after 3.5 hours and 5.5 hours, sulfuryl chloride (1.8%) was added. ml, 22.4 ol) and heated under reflux for a total of 6 hours.
  • aqueous thorium solution was added, and the organic layer was separated.
  • the aqueous layer was extracted with methylene chloride (20 ml x 2), washed with water (50 ml) and saturated saline (50 ml) together with the previous organic layer, dried over anhydrous sodium sulfate, and then depressurized. The solvent was distilled off underneath.
  • 2-chloro-monochloromethylpyridines ( ⁇ ), 2-chloro-monochloromethylpyridines (II) and 2-chloro-trichloromethylpyridine which are intermediates for the production of pharmaceuticals and agricultural chemicals
  • the compound (IV) can be produced easily and in good yield from the methyl-2-sulfonylpyridine (I).
  • the starting compound methyl-2-sulfonyl pyridines (I) can be produced in good yield at low cost from, for example, sulfonyl cyanide (V) and methyl-substituted 1-acyloxy 1,3-butadiene (VI).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

La présente invention concerne des 2-chloropyridines représentées par les formules générales (II), (III) et/ou (IV) et qui sont des produits intermédiaires dans la fabrication de médicaments et de pesticides. Elles peuvent être produites avec efficacité et facilité par le traitement de méthyl-2-sulfonylpyridines, représentées par la formule générale (I), avec des agents de chloration, dans des conditions permettant la formation de radicaux libres. Dans ces formules (I), (II), (III) et (IV), R1 représente alkyle inférieur, cycloalkyle, aryle ou aralkyle éventuellement substitué. En outre, on peut fabriquer les produits de départ (I) de manière efficace, avec un bon rendement et pour un faible coût, en faisant réagir du cyanure de sulfonyle avec un 1-acyloxy-1,3-butadiène substitué par du méthyle.
PCT/JP1996/000383 1995-02-22 1996-02-21 2-chloropyridines et procede de fabrication des produits de depart associes Ceased WO1996026188A1 (fr)

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
JP3320895 1995-02-22
JP7/33209 1995-02-22
JP7/33208 1995-02-22
JP3320995 1995-02-22
JP7/196603 1995-08-01
JP19660395 1995-08-01
JP7/196604 1995-08-01
JP19660495 1995-08-01
JP21606795 1995-08-24
JP7/216068 1995-08-24
JP21606895 1995-08-24
JP7/216067 1995-08-24

Publications (1)

Publication Number Publication Date
WO1996026188A1 true WO1996026188A1 (fr) 1996-08-29

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PCT/JP1996/000383 Ceased WO1996026188A1 (fr) 1995-02-22 1996-02-21 2-chloropyridines et procede de fabrication des produits de depart associes

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998011071A1 (fr) * 1996-09-10 1998-03-19 Kuraray Co., Ltd. Procede pour la preparation de derives d'halogenopyridine
EP0931790A3 (fr) * 1998-01-26 1999-08-18 Kuraray Co., Ltd. Procédé pour la préparation de dérivées de 2-sulfonylpyridine et de dérivés de 2-( (2-pyridyl)méthyl)thio)-1H-benzimidazole
US6350876B2 (en) 1998-01-26 2002-02-26 Kuraray Co., Ltd. 4-chloro-3,5-dimethyl-2-sulfonyl pyridines

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60130529A (ja) * 1983-12-19 1985-07-12 Asahi Glass Co Ltd ジアゾフツ素化方法
JPS61277666A (ja) * 1985-05-30 1986-12-08 ザ　ダウ　ケミカル　カンパニ− 触媒使用による塩素化β−（トリクロロメチル）ピリジンからの対称テトラクロロピリジンの製造法
JPH04330056A (ja) * 1990-01-31 1992-11-18 Bayer Ag ２−クロロ−５−メチル−ピリジンの製造方法
JPH0656782A (ja) * 1991-11-26 1994-03-01 Dowelanco ２，３，５，６−テトラクロロピリジンおよびその先駆体を製造するための多塩素化されたβ−ピコリン類の選択的気相塩素化

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS60130529A (ja) * 1983-12-19 1985-07-12 Asahi Glass Co Ltd ジアゾフツ素化方法
JPS61277666A (ja) * 1985-05-30 1986-12-08 ザ　ダウ　ケミカル　カンパニ− 触媒使用による塩素化β−（トリクロロメチル）ピリジンからの対称テトラクロロピリジンの製造法
JPH04330056A (ja) * 1990-01-31 1992-11-18 Bayer Ag ２−クロロ−５−メチル−ピリジンの製造方法
JPH0656782A (ja) * 1991-11-26 1994-03-01 Dowelanco ２，３，５，６−テトラクロロピリジンおよびその先駆体を製造するための多塩素化されたβ−ピコリン類の選択的気相塩素化

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SYNTHESIS, No. 8, (1989), pages 623-625. *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998011071A1 (fr) * 1996-09-10 1998-03-19 Kuraray Co., Ltd. Procede pour la preparation de derives d'halogenopyridine
US6118005A (en) * 1996-09-10 2000-09-12 Kuraray Co., Ltd. Process for preparing halogenopyridine derivatives
EP0931790A3 (fr) * 1998-01-26 1999-08-18 Kuraray Co., Ltd. Procédé pour la préparation de dérivées de 2-sulfonylpyridine et de dérivés de 2-( (2-pyridyl)méthyl)thio)-1H-benzimidazole
US6197962B1 (en) 1998-01-26 2001-03-06 Kuraray Co., Ltd. Method for producing 2-sulfonylpyridine derivatives and method for producing 2-{[(2-pyridyl)methyl]thio}-1H-benzimidazole derivatives
US6350876B2 (en) 1998-01-26 2002-02-26 Kuraray Co., Ltd. 4-chloro-3,5-dimethyl-2-sulfonyl pyridines

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