WO1998056777A1 - Benzenes isoxazol-5-yl-substitues et leur procede de production - Google Patents

Benzenes isoxazol-5-yl-substitues et leur procede de production Download PDF

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Publication number
WO1998056777A1
WO1998056777A1 PCT/JP1998/002537 JP9802537W WO9856777A1 WO 1998056777 A1 WO1998056777 A1 WO 1998056777A1 JP 9802537 W JP9802537 W JP 9802537W WO 9856777 A1 WO9856777 A1 WO 9856777A1
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WIPO (PCT)
Prior art keywords
methyl
solvent
compound
acid
benzene
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PCT/JP1998/002537
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English (en)
French (fr)
Japanese (ja)
Inventor
Michinori Takebayashi
Masami Hatano
Hiroyuki Adachi
Takashi Okabe
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Nippon Soda Co., Ltd.
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Application filed by Nippon Soda Co., Ltd. filed Critical Nippon Soda Co., Ltd.
Priority to AU75525/98A priority Critical patent/AU7552598A/en
Publication of WO1998056777A1 publication Critical patent/WO1998056777A1/ja

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D261/00Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/08Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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 novel isoxazole-5-yl-substituted benzenes useful as intermediates for agricultural chemicals and pharmaceuticals, and a method for producing the same.
  • Background art :
  • Compounds derived from the isooxazole-5-yl-substituted benzenes of the present invention include W096 / 26206, W0997 / 4111, W0997 / 4 No. 118 discloses that compounds represented by the following formula [A] are useful as herbicides.
  • the present invention provides a compound represented by the general formula [I]:
  • R represents a chlorine atom or a methyl group
  • R 1 , R 2 and R 3 represent Each independently represents a hydrogen atom or a C, -4 alkyl group.
  • the alkyl groups for R ′, R 2 and R 3 include, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl and the like. Is mentioned.
  • the production method of the compound of the present invention and various intermediate compounds will be described in more detail. Production Method 1
  • Compound [I] of the present invention can be produced by reacting compound [H] with alkanethiol [IE] in a suitable solvent in the presence of a base at a temperature between 0 and the boiling point of the solvent used. .
  • alkanthiol used in the reaction examples include methyl menolecaptan, ethyl mercaptan, n-propylmercaptan, and isopropylmercaptan, and the base is sodium methanol.
  • salts of sodium, potassium and the like of the previously prepared alkanol [IE] can also be used.
  • solvent used examples include alcohols such as methanol, ethanol and isopropanol, ethers such as THF and dioxane, and aromatic hydrocarbons such as bemben, toluene, and xylene. And nitriles such as acetate, and amides such as DMF and dimethyl acetate.
  • Compound [I] is prepared by converting compound [IV] into Na N02 or a general formula: in a suitable solvent, in the presence of an organic acid such as acetic acid or a mineral acid such as hydrochloric acid or sulfuric acid, at a temperature from room temperature to 0 ° C.
  • R 0 N 0 R is, C, -. indicating an e alkyl group
  • Examples of the solvent used include water, acids such as acetic acid, alcohols such as methanol, ethanol and isopropanol, nitriles such as acetonitrile, acetate and methylethylketo. Ketones such as methane, ethers such as THF and dioxane, esters such as ethyl acetate, DMF and the like, or a mixed solvent of two or more of these.
  • Hydrolysis in alcohol is more mild in the presence of copper, aluminum, copper oxide, zinc dust or a large excess of hypophosphorous acid, or using a catalyst such as copper sulfate.
  • the reaction can also be performed under conditions.
  • compound [IV] is converted to an alcohol such as methanol, ethanol or propanol in an appropriate solvent in the presence of an organic acid such as acetic acid or a mineral acid such as hydrochloric acid or sulfuric acid. It can be added and reacted under heating with NaN 02 or R 1 ON ⁇ .
  • the compound [H] and the compound [IV] in the above Production Method 1 and Production Method 2 are both novel compounds, and can be produced, for example, by the following method.
  • R 5 represents R 5 ′ because it may scramble with R 6 of Mg (OR 6 ).
  • the diketoester (4) can be produced from the benzoic acid halide (3) and the magnesium salt of the / 3-ketoester (2) by a known method.
  • the / 3-ketoester (1) and the magnesium alcoholate (2) are reacted in a suitable solvent at a temperature between 0 ° C and the boiling point of the solvent used for 0.5 to 10 hours, To a magnesium salt of a ketoester and then reacting with benzoic acid halide (4) at a temperature between 110 ° C and the boiling point of the solvent used.
  • the reaction By removing the alcohol by-produced during the production of magnesium salt in this reaction, the reaction can be carried out smoothly and the by-product can be reduced.
  • solvent used in this reaction examples include aromatic hydrocarbons such as benben, toluene, and xylene; aliphatic hydrocarbons such as n-hexane and cyclohexane; ethers and tetrahydrofuran ( Ethers such as THF) and dioxane.
  • Step b
  • Compound (5) exists as a tautomer of keto and enol, and at room temperature, rather, exists mostly as an enol form.
  • solvent used examples include aromatic hydrocarbons such as benben, toluene, and xylene; aliphatic hydrocarbons such as n-hexane and cyclohexane; ethers such as ether, THF and dioxane; and chlorobenzene. And the like, and halogenated hydrocarbons.
  • the reaction time varies depending on the substituents, but is generally from several hours to 48 hours.
  • the amount of the acid catalyst used is from 0.001 to 1 mol per 1 mol of the compound (4).
  • compound (5) can also be produced by acid-catalyzed hydrolysis. That is, it can be produced by hydrolyzing compound (4) in the presence of a mineral acid such as hydrochloric acid or sulfuric acid at a temperature between room temperature and the boiling point of the solvent used for several hours to 48 hours.
  • a mineral acid such as hydrochloric acid or sulfuric acid
  • water-soluble ethers such as acetic acid, THF, and dioxane
  • alcohols such as methanol, ethanol, and isopropanol
  • a mixed solvent of two or more of these are used together with water. Can be performed smoothly.
  • the compound [ ⁇ ] is reacted by reacting the diketone compound (5) with hydroxylamin in a suitable solvent at 0 ° C. and at the boiling point of the solvent used for i 0 minutes to 24 hours. Can be manufactured.
  • the hydroxylamine can be used in the form of a hydrochloride or a sulfate, or an acid such as hydrogen chloride, sulfuric acid or P-toluenesulfonic acid can be used as a catalyst.
  • the solvent examples include alcohols such as methanol, ethanol and isopropanol; hydrocarbons such as benzene and toluene; ethers such as THF and dioxane; Examples include nitriles such as nitrile, dimethylformamide (DMF), pyridine, acetic acid, water, etc., and a mixed solvent of two or more of these solvents.
  • alcohols such as methanol, ethanol and isopropanol
  • hydrocarbons such as benzene and toluene
  • ethers such as THF and dioxane
  • nitriles such as nitrile, dimethylformamide (DMF), pyridine, acetic acid, water, etc., and a mixed solvent of two or more of these solvents.
  • R, R 1 , R 2 , R 5 , R 6 , R 5 ′ and have the same meanings as described above.
  • R 7 represents SCN, chlorine atom or bromine atom.
  • the diketoester (7) can be produced from the benzoic acid halide (6) and the magnesium salt of the -ketoester (1) in the same manner as in the step a).
  • the compound (7) is heated in a suitable solvent in the presence of a catalytic amount of a mineral acid such as hydrochloric acid or sulfuric acid or an organic acid such as p-toluenesulfonic acid at a temperature up to the boiling point of the solvent to be used. 8) can be manufactured.
  • a mineral acid such as hydrochloric acid or sulfuric acid or an organic acid such as p-toluenesulfonic acid
  • the compound (8) exists as a tautomer of a ketone and an enol, and at room temperature, rather, exists mostly as an enol form.
  • the solvent to be used include aromatic hydrocarbons such as benzene and toluene and xylene, aliphatic hydrocarbons such as n-hexane and cyclohexane, ethers such as ether, THF, and dioxane; Halogenated hydrocarbons such as chlorobenzene;
  • the reaction time varies depending on the substituents, but is generally from several hours to 48 hours.
  • the amount of the acid catalyst used is from 0.001 to 2 mol per 1 mol of the compound (7).
  • compound (8) can also be produced by acid-catalyzed hydrolysis. That is, it can be produced by hydrolyzing compound (7) in the presence of a mineral acid such as hydrochloric acid or sulfuric acid at a temperature between room temperature and the boiling point of the solvent used for several hours to 48 hours. In this reaction, water and water-soluble ethers such as acetic acid, THF, and dioxane; alcohols such as methanol, ethanol, and isopropanol; or a mixture of two or more of these, with water. The reaction can be carried out smoothly by using a solvent.
  • a mineral acid such as hydrochloric acid or sulfuric acid
  • hydroxylamin can be used in the form of a hydrochloride or a sulfate, or an acid such as hydrogen chloride, sulfuric acid or p-toluenesulfonic acid can be used as a catalyst.
  • the solvent examples include alcohols such as methanol, ethanol and isopropanol; hydrocarbons such as benzene and toluene; ethers such as THF and dioxane; and acetates such as acetonitril.
  • examples include nitriles, DMF, pyridine, acetic acid, water, and the like, and a mixed solvent of two or more of these solvents.
  • the compound (10) is obtained by reduction with a metal and an acid or catalytic reduction using a catalyst.
  • a metal Fe, Zn, S ⁇ or the like or a compound thereof is used, and is used in the form of powder, granules or rods.
  • an organic acid such as acetic acid and a spreading acid such as hydrochloric acid and sulfuric acid are used.
  • solvent used examples include water, acids such as acetic acid, alcohols such as methanol, ethanol and isopropanol, ketones such as acetone and methylethylketone, THF, dioxane and the like. And DMF and the like, or a mixed solvent of two or more thereof.
  • Catalytic reduction is performed under normal pressure or pressurization of hydrogen gas.
  • a catalyst 0.1 to 10% of PdZC, PdZBaSO ,,, Pt / C, or the like is used.
  • solvent used examples include water, acids such as acetic acid, alcohols such as methanol, ethanol, and isopropanol; ketones such as acetate and methylethylketone; and ethers such as THF and dioxane. And the like.
  • the isooxazole ring may be opened. In such a case, it is necessary to use a less active catalyst. In some cases, the compound in which the isoxazole ring has been opened can be reacted again with NH 2 OH.HCl to close the isoxazole ring.
  • Compound (11) is produced by reacting 1 to 2 moles of (R 8 ) 2 with respect to 1 mole of compound (10) in an appropriate solvent at a temperature between 0 and the boiling point of the solvent used. it can.
  • Examples of (R 7 ) 2 include (SCN) 2 , (Br) 2 , (C 1) 2 and the like, and (SCN) 2 is converted into Na SCN, KSCN or NH 4 SCN during the reaction. It is also possible to use those that have been reacted with halogens such as Br 2 and C 12, N-chloroamide, calcium hypochlorite, and the like.
  • Solvents used include water, acids such as acetic acid, methanol, ethanol, Examples thereof include alcohols such as propanol, ketones such as acetone and methylethyl ketone, ethers such as THF and dioxane, DMF and the like, and a mixed solvent of two or more of these.
  • Compound (IV) is prepared by subjecting compound (11) to an appropriate solvent at a temperature between 0 ° C. and the boiling point of the solvent to be used.
  • KS can be produced by reacting R 3 Z or (R 30 ) SO 2 (R 3 , Z has the same meaning as described above).
  • the solvent used include water, acids such as acetic acid, alcohols such as methanol, ethanol and isopropanol, ketones such as acetone and methylethylketone, THF, dioxane and the like. Ethers, DMF and the like, or a mixed solvent of two or more thereof.
  • the benzoic acid represented by the general formula [V] can be produced from the compound of the present invention by the method shown below.
  • R 8 represents a halogen atom or an optionally substituted methyl group
  • Y represents a halogen atom or R 8 represents a CO ⁇ group
  • n represents 1 or 2.
  • the compound (13) is obtained by adding 1 to 2 mol of the compound (12) to 1 mol of the compound [I] without solvent or in an appropriate solvent, and mixing 1 to 5 mol of a Louis acid such as aluminum chloride. And at a temperature between 110 and the boiling point of the solvent used.
  • Examples of the compound (12) include acid halides such as acetyl chloride and propionyl chloride, and acid anhydrides such as acetic anhydride and butyric anhydride.
  • Examples of the solvent to be used include chlorinated hydrocarbons such as methylene chloride and chloroform.
  • Compound [V] can be produced by reacting compound (13) with 5- to 10-fold molar hypohalogenate in an appropriate solvent at —10 to 80.
  • hypohalite examples include sodium hypochlorite, sodium hypobromite, potassium hypochlorite, calcium hypochlorite, and the like.
  • Water is generally used as the reaction solvent, but a mixed solvent with dioxane or the like can also be used for smooth reaction.
  • This reaction may be carried out in a single step, but in some cases, the reaction may be carried out under milder conditions, for example, by reacting the first step with aqueous hydrogen peroxide and then with a hypohalite. it can.
  • the target product can be obtained by performing ordinary post-treatment after completion of any of the reactions.
  • the structure of the compound of the present invention was determined from IR, NMR, MS and the like.
  • the R 4 C is as one ⁇ alkyl group, methylation, Echiru, pro Pi Le, i Sopuro pills, heptyl, I Sopuchiru, s - heptyl, t - like butyl cited et al is, R Examples of the C i-optionally branched alkyl group of 5 , R 6 and R 5 ′ include methyl, ethyl, propyl, isopropyl, butyl, isoptyl, s-butyl, t-butyl, Examples include amimil, isoamyl, hexyl, isohexyl, 4-methyl-2-pentyl, and 2-ethylbutyl.
  • halogen atoms for X and Y include chlorine and bromine.
  • methyl group which may be substituted with the halogen atom of R 7 include methyl, chloromethyl, bromomethyl, fluoromethyl, trimethyl, dichloromethyl, and trimethyl.
  • 2-methyl-6-thiocyanato-1-1 (3-methylisoxazole-5-yl) benzene 1.18 g was obtained. Further, the mother liquor was concentrated under reduced pressure, a small amount of ethanol was added, crystallization and filtration were performed. Further, 0.94 g of 3-amino-2-methyl-6-thiocyanato 1— was added. (3—Methyl Louis Soxazole—5—yl) Benzene was obtained.
  • the reaction mixture was washed with 1N-hydrochloric acid and then with saturated saline, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • the residue was dissolved in 20 ml of acetonitrile, and 0.47 g (0.047 mol) of triethylamine and 0.1 g of acetonitrile (0.04 mol) were added. (0.11 mol) and stirred at room temperature overnight.
  • the solvent was distilled off under reduced pressure, and the residue was dissolved in ethyl acetate, washed with 1 N hydrochloric acid and then with saturated saline, dried over anhydrous magnesium sulfate, and then the solvent was distilled off.
  • the residue was purified by silica gel column chromatography to obtain 0.73 g of the desired compound as crystals. m.p. 2 3 0-23 3 ° C
  • This compound showed strong herbicidal activity.
  • Hydrochloric acid 1 methyl mono 5—hydroxypyrazole 0.36 g (0.0026 mol) and triethylamine 0.51 g (0.0051 mol) are mixed with methyl chloride. Dissolved in 10 mi of ren, and 2-methyl 4-methanesulfonyl 3-(3-methylisoxazolo 1-5-yl) benzoyl chloride 0.71 g (0.02) 3 mol) methylene chloride solution 2 ml was added dropwise at room temperature, and the mixture was further stirred at room temperature for 1 hour. The reaction mixture was washed with 1N hydrochloric acid and then with a saturated saline solution, dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • the production method of the present invention can be easily produced with a high yield, and various intermediates are industrially used as intermediates for agricultural chemicals and pharmaceuticals, for example, as intermediates for herbicides. It is a useful compound.
PCT/JP1998/002537 1997-06-10 1998-06-09 Benzenes isoxazol-5-yl-substitues et leur procede de production WO1998056777A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU75525/98A AU7552598A (en) 1997-06-10 1998-06-09 Isoxazol-5-yl-substituted benzenes and process for producing the same

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
JP9/167940 1997-06-10
JP16794097 1997-06-10
JP9/196464 1997-07-07
JP19646497 1997-07-07
JP24193997 1997-08-22
JP9/241939 1997-08-22

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999064404A1 (fr) * 1998-06-05 1999-12-16 Nippon Soda Co., Ltd. Composes thio phenoles a groupes heterocycliques, produits intermediaires utiles pour la preparation de ceux-ci et leurs procedes de preparation

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2265371A (en) * 1992-03-06 1993-09-29 Shell Int Research Isoxazole compounds
WO1994017059A1 (en) * 1993-01-29 1994-08-04 Nippon Soda Co., Ltd. Heterocyclic derivative
WO1996026206A1 (de) * 1995-02-24 1996-08-29 Basf Aktiengesellschaft Pyrazol-4-yl-benzoylderivate und ihre verwendung als herbizide
WO1997035850A1 (fr) * 1996-03-26 1997-10-02 Nippon Soda Co., Ltd. Derives d'acide benzoique a substitution 3-(isoxazol-5-yl) et leur procede de production

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2265371A (en) * 1992-03-06 1993-09-29 Shell Int Research Isoxazole compounds
WO1994017059A1 (en) * 1993-01-29 1994-08-04 Nippon Soda Co., Ltd. Heterocyclic derivative
WO1996026206A1 (de) * 1995-02-24 1996-08-29 Basf Aktiengesellschaft Pyrazol-4-yl-benzoylderivate und ihre verwendung als herbizide
WO1997035850A1 (fr) * 1996-03-26 1997-10-02 Nippon Soda Co., Ltd. Derives d'acide benzoique a substitution 3-(isoxazol-5-yl) et leur procede de production

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999064404A1 (fr) * 1998-06-05 1999-12-16 Nippon Soda Co., Ltd. Composes thio phenoles a groupes heterocycliques, produits intermediaires utiles pour la preparation de ceux-ci et leurs procedes de preparation

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