WO2014192841A1 - Procédé de production de composé isoxazoline optiquement actif - Google Patents

Procédé de production de composé isoxazoline optiquement actif Download PDF

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Publication number
WO2014192841A1
WO2014192841A1 PCT/JP2014/064204 JP2014064204W WO2014192841A1 WO 2014192841 A1 WO2014192841 A1 WO 2014192841A1 JP 2014064204 W JP2014064204 W JP 2014064204W WO 2014192841 A1 WO2014192841 A1 WO 2014192841A1
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group
compound
substituent
phenyl
mmol
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PCT/JP2014/064204
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English (en)
Japanese (ja)
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維奇 王
宮本　隆史
崇 三木
池本　哲哉
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住友化学株式会社
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Definitions

  • the present invention relates to a method for producing an optically active isoxazoline compound.
  • the compound represented by the formula (2) (wherein each symbol is as described below)
  • WO2010 / 090344 it is known to be useful as an active ingredient of a pest control agent and an intermediate for the production thereof.
  • WO2009 / 063910 and Angewante Chemie, International Edition (2010), 49 (33), 5762-5766 a compound represented by the formula (1) and a hydroxyamine are mixed between a chiral phase in a solvent in the presence of a base and water. It has been shown that an optically active compound represented by the formula (2) can be produced by adding a transfer catalyst and reacting it.
  • the present invention provides a novel method for producing an optically active compound represented by the formula (2).
  • the compound represented by the formula (1) and hydroxyamine are reacted with any one selected from the compounds described in group 1 described later and enantiomers thereof and carbonate.
  • an optically active compound represented by the formula (2) can be produced.
  • Ar has a phenyl group which may have a substituent, a naphthyl group which may have a substituent, an indanyl group which may have a substituent, or a substituent.
  • Ar 1 and Ar 2 represent a phenyl group which may have a substituent
  • R 1 and R 2 are the same or different and represent a phenyl group which may have a substituent.
  • R 1 and R 2 together represent — (CH 2 ) u —
  • u represents an integer of 2 to 6
  • R 3 and R 4 are the same or different
  • R 3 and R 4 together represent — (CH 2 ) v —
  • v is an integer of any one of 2 to 6
  • R 5 and R 6 are the same or different and may have a phenyl group.
  • Ar 3 represents an optionally substituted quinolyl group, and the hydrogen atom bonded to the carbon atom of the compound described in Group 1 may be substituted). Or an enantiomeric compound thereof.
  • the halogen atom is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.
  • examples of the C1-C12 alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, and a neopentyl group.
  • a C1-C6 alkyl group is preferable and a C1-C4 alkyl group is more preferable.
  • examples of the C1-C6 alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, and a neopentyl group.
  • C1-C4 alkyl Group 1-ethylpropyl group, hexyl group, isohexyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 3,3-dimethylbutyl group and 2-ethylbutyl group, C1-C4 alkyl Group is preferable, and a methyl group and an ethyl group are more preferable.
  • examples of the C1-C4 alkyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group.
  • examples of the C1-C3 alkyl group optionally having a phenyl group include a methyl group, an ethyl group, a propyl group, an isopropyl group, and a 3-phenylpropyl group, and a 3-phenylpropyl group.
  • examples of the C3-C8 cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group, and a C3-C6 cycloalkyl group is preferable.
  • examples of the C3-C6 cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
  • examples of the C2-C12 alkoxycarbonyl group include a methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, isobutoxycarbonyl group, sec-butoxycarbonyl group, tert- Examples thereof include a butoxycarbonyl group, a pentyloxycarbonyl group, an isopentyloxycarbonyl group, a neopentyloxycarbonyl group, and a hexyloxycarbonyl group, and a C2-C6 alkoxycarbonyl group is preferable.
  • examples of the C2-C6 alkoxycarbonyl group include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group, a sec-butoxycarbonyl group, and a tert- Examples include butoxycarbonyl group and pentyloxycarbonyl group.
  • examples of the C2-C12 alkylcarbonyl group include acetyl group, propionyl group, butyryl group, isobutyryl group, valeryl group, isovaleryl group, pivaloyl group, lauroyl group and the like, and C2-C6 alkylcarbonyl group Is preferred.
  • examples of the C2-C6 alkylcarbonyl group include an acetyl group, a propionyl group, a butyryl group, an isobutyryl group, a valeryl group, an invaleryl group, and a pivaloyl group.
  • examples of the C6-C14 aryl group include a phenyl group, a naphthyl group, an anthryl group, a phenanthryl group, an acenaphthylenyl group, and a biphenylyl group, and a C6-C10 aryl group is preferable.
  • examples of the C6-C10 aryl group include a phenyl group and a naphthyl group.
  • examples of the benzyl group optionally having a substituent on the benzene ring include a benzyl group and a 4-methoxybenzyl group, and a benzyl group is preferable.
  • examples of the phenyl group optionally having one or more halogen atoms include a phenyl group, a 3,5-dichlorophenyl group, and a 3,5-dichloro-4-fluorophenyl group.
  • a 3,5-dichlorophenyl group is preferred.
  • examples of the substituent in the phenyl group, naphthyl group, indanyl group or indolizinyl group which may have a substituent include the following substituent B.
  • the following substituent B is mentioned also as a substituent of the phenyl group which may have a substituent, and the quinolyl group which may have a substituent.
  • Y represents any one group in group 1 (provided that the hydrogen atom bonded to the carbon atom of the group in group 1 may be substituted), and the substituent B is as follows: Is mentioned.
  • [Substituent B] C1-C6 alkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C8 cycloalkyl group, C3-C8 cycloalkenyl group, C4-C8 cycloalkadienyl group, C6-C14 aryl group, C7-C16 An aralkyl group, a heterocyclic group; Hydroxy group, C1-C6 alkoxy group, C2-C6 alkenyloxy group, C2-C6 alkynyloxy group, C3-C8 cycloalkyloxy group, C3-C8 cycloalkenyloxy group, C4-C8 cycloalkadienyloxy group, C6 -C14 aryl
  • the number of substituents is not particularly limited as long as it is a substitutable number, but is preferably 1 to 5, more preferably 1 to 3. When a plurality of substituents are present, each substituent may be the same or different.
  • the above substituent may further have a substituent A.
  • Ar is preferably a phenyl group which may have one or more selected from the group consisting of a halogen atom and the following group.
  • R 7 represents a C 3-8 cycloalkyl group
  • R 8 and R 9 are the same or different and each represents a hydrogen atom, a formyl group, a C1-C12 alkyl group, a C2-C12 alkoxycarbonyl group
  • a C2- represents a C12 alkylcarbonyl group or a C6-C14 aryl group
  • X 1 and X 2 are the same or different and each represents a hydrogen atom, a formyl group, a C2-C12 alkylcarbonyl group, a C2-C12 alkoxycarbonyl group, an allyloxycarbonyl group, A benzyloxycarbonyl group or a benzyl group optionally having a substituent on the benzene ring, and * represents a binding site).
  • R 7 is a C3-C8 cycloalkyl group
  • R 8 and R 9 are a hydrogen atom, a C1-C12 alkyl group or a C2-C12 alkoxycarbonyl group
  • X 1 and X 2 In which is a hydrogen atom.
  • Particularly preferred examples of Ar are 4-chlorophenyl group and 3- (2-cyclopropanecarbohydrazino) -4-chlorophenyl group.
  • Ar 1 is preferably a phenyl group which may have one or more selected from the group consisting of a halogen atom and a trifluoromethyl group, and particularly preferably 3,5-dichlorophenyl group, 3-chloro-5-triphenyl.
  • Ar 2 is preferably a phenyl group which may have one or more selected from the group consisting of a nitro group and a trifluoromethyl group.
  • Ar 2 is more preferably a phenyl group optionally having one or more trifluoromethyl groups, and particularly preferably a 3,5-ditrifluoromethylphenyl group.
  • a compound represented by the formula (1) and a hydroxyamine are combined with any one selected from the compounds described in Group 1 and enantiomers thereof and a carbonate.
  • an optically active compound represented by the formula (2) is synthesized (isoxazoline ring formation reaction).
  • the optical activity means that a compound having an asymmetric carbon contains one enantiomer in excess relative to the other enantiomer, or only one enantiomer is included. Represents the state of being.
  • Specific examples of the compounds described in Group 1 and their enantiomeric compounds include the following compounds. Among these, the following compounds are preferable because a product having high optical purity can be obtained.
  • the compounds described in Group 1 and their enantiomeric compounds may be commercially available products, or may be produced according to known methods. For example, it can manufacture according to the method as described in USP7632970 or OrganicLetters 14 (2012) 3296-3299.
  • the amount of the compound described in Group 1 and its enantiomeric compound is usually 0.1% with respect to the compound represented by formula (1) from the viewpoint of yield and economy. It is ⁇ 50 mol%, preferably 0.5 to 20 mol%.
  • the compound represented by the formula (1) used as a raw material may be a commercially available product, or may be produced according to a known method. For example, it can be produced according to the method described in EP2716628.
  • Examples of the hydroxylamine used in the isoxazoline ring formation reaction include hydroxylamine and its salt with a mineral acid such as hydrochloric acid. Hydroxylamine may be used as it is or in the form of an aqueous solution. The amount of hydroxylamine to be used is usually 1 to 20 moles, preferably 1 to 10 moles, relative to the compound represented by the formula (1) from the viewpoint of yield and economy.
  • Examples of the carbonate used in the isoxazoline ring formation reaction include alkali metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, and cesium carbonate, and alkaline earth metal carbonates such as magnesium carbonate, calcium carbonate, and barium carbonate. Can be mentioned.
  • alkali metal carbonates are preferable, and cesium carbonate is particularly preferable.
  • the amount of the carbonate used is usually 1 to 10 mol times, preferably 1 to 5 mol times based on the compound represented by the formula (1).
  • the isoxazoline ring formation reaction may be performed by adding an inorganic oxide.
  • the inorganic oxide include aluminum oxide (alumina), magnesium oxide, calcium oxide, and the like. Aluminum oxide and magnesium oxide are preferable, and aluminum oxide is particularly preferable.
  • the amount of the inorganic oxide used is usually 0.1 to 10 times by weight, preferably 0.1 to 2 times by weight, relative to the compound represented by the formula (1).
  • the isoxazoline ring formation reaction is usually performed in a solvent.
  • the solvent examples include aliphatic hydrocarbon solvents such as hexane, cyclohexane and heptane; aromatic hydrocarbon solvents such as toluene, xylene and mesitylene; aliphatic halogenated hydrocarbon solvents such as chloroform, dichloromethane and butane chloride; chlorobenzene, Aromatic halogenated hydrocarbon solvents such as dichlorobenzene, fluorobenzene and trifluoromethylbenzene; ether solvents such as tert-butyl methyl ether, tetrahydrofuran and cyclopentyl methyl ether; nitrile solvents such as acetonitrile; N, N-dimethylformamide and the like Amide solvents and mixed solvents thereof are preferable, and from the viewpoint of reactivity and selectivity, aliphatic halogenated hydrocarbon solvents, aromatic halogenated hydrocarbon solvents, and aromatic hydrocarbon solvents are preferable, and chloro
  • the amount of the solvent used is usually 1 to 100 times by weight, preferably 1 to 30 times by weight with respect to the compound represented by the formula (1).
  • the isoxazoline ring formation reaction is preferably performed within a range of ⁇ 30 to 60 ° C., more preferably within a range of ⁇ 10 to 30 ° C., and the reaction time is preferably 0.5 to 100 hours, more preferably 1 to 48 hours.
  • the progress of the isoxazoline ring formation reaction can be confirmed by analytical means such as thin layer chromatography, gas chromatography, high performance liquid chromatography and the like.
  • the post-treatment of the isoxazolinization reaction can be performed by subjecting the reaction mixture to conventional methods (for example, neutralization, extraction, washing with water, distillation, crystallization, etc.). Further, the purification is performed by subjecting the optically active compound represented by the formula (2) to recrystallization treatment, extraction purification treatment, distillation treatment, adsorption treatment of activated carbon, silica gel, alumina and the like, and chromatography treatment such as silica gel column chromatography. It can be carried out.
  • Example 5 The HPLC analysis of Example 5 was performed under the following conditions. Yield analysis conditions: The measurement was performed according to the HPLC conditions described in Examples 1 to 4. Retention time Compound 1b 6.7 min, Compound 2b 7.1 min The yield was calculated as the area of the compound 2b percentage / (area percent area percent + Compound 2b of compound 1b).
  • Example 9 Synthesis of Compound 2b (2- ⁇ 2-chloro-5- [3- (3,5-dichlorophenyl) 4,5-dihydro-5- (trifluoromethyl) -3-isoxazoyl] phenyl ⁇ cyclopropanecarbohydrazide)
  • Compound 1b (2- ⁇ 2-chloro-5- [3- (3,5-dichlorophenyl) -4,4,4-trifluoro-1-oxo-2-buten-1-yl] phenyl ⁇ cyclopropanecarbohydrazide ) (48 mg, 0.1 mmol), compound (S) -C- 5 (8 mg, 0.02 mmol), cesium carbonate (98 mg, 0.3 mmol), and chlorobenzene (2 mL) are mixed, and the temperature of
  • Example 12 Compound A Synthesis of ethyl 2-( ⁇ 2-chloro-5- [5- (3,5-dichlorophenyl) -4,5-dihydro-5-trifluoromethyl-3-isoxazolyl] phenyl ⁇ hydrazono) propionate
  • Compound a 2-( ⁇ 2-chloro-5- [3- (3,5-dichlorophenyl) -4,4,4-trifluoro-1-oxo-2-buten-1-yl] phenyl ⁇ hydrazono) propionic acid Mix ethyl (50 mg, 0.10 mmol), (9R) -CINN-TC (11 mg, 0.02 mmol), cesium carbonate (96 mg, 0.30 mmol) and chlorobenzene (1 mL) and adjust the temperature of the mixture to 0 ° C.
  • Example 14 Compound C 2-( ⁇ 2-chloro-5- [5- (3,5-dichlorophenyl) -4,5-dihydro-5-trifluoromethyl-3-isoxazolyl] phenyl ⁇ hydrazono) -3-phenylpropionate Synthesis of Compound c 2-( ⁇ 2-chloro-5- [3- (3,5-dichlorophenyl) -4,4,4-trifluoro-1-oxo-2-buten-1-yl] phenyl ⁇ hydrazono) -3 -Ethyl phenylpropionate (48 mg, 0.083 mmol), (9R) -CINN-TC (9 mg, 0.016 mmol), cesium carbonate (84 mg, 0.26 mmol) and chlorobenzene (1 mL) were mixed and the temperature of the mixture was After adjusting to 0 ° C., 50% aqueous hydroxyamine solution (34 mg, 0.51 mmol) was added.
  • Example 15 Compound D 2-( ⁇ 2-chloro-5- [5- (3,4,5-trichlorophenyl) -4,5-dihydro-5-trifluoromethyl-3-isoxazolyl] phenyl ⁇ hydrazono) ethyl propionate
  • Composition Compound d 2-( ⁇ 2-chloro-5- [3- (3,4,5-trichlorophenyl) -4,4,4-trifluoro-1-oxo-2-buten-1-yl] phenyl ⁇ hydrazono )
  • Ethyl propionate (137 mg, 0.25 mmol), (9R) -CINN-TC (29 mg, 0.05 mmol), cesium carbonate (163 mg, 0.50 mmol) and chlorobenzene (1.76 g) were mixed and the temperature of the mixture was adjusted to 20-25 ° C., and 50% aqueous hydroxyamine solution (50 mg, 0.75 mmol) was added.
  • An optically active isoxazoline compound can be produced by the method of the present invention.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

L'invention porte sur un composé isoxazoline optiquement actif représenté par la formule (2) pouvant être produit par la réaction d'un composé représenté par la formule (1) avec de l'hydroxylamine en présence à la fois, d'au moins un composé choisi parmi les composés cités dans le groupe 1 et les composés énantiomères de ceux-ci et d'un sel carbonate. (Dans les formules, Ar représente un groupe phényle qui peut avoir un substituant ou analogue ; Ar1 et Ar2 représentent indépendamment un groupe phényle qui peut avoir un substituant ; R1 et R2 sont identiques ou différents l'un de l'autre et représentent indépendamment un groupe phényle qui peut avoir un substituant ou analogue ; R3 et R4 sont identiques ou différents l'un de l'autre et représentent indépendamment un groupe alkyle en C1-C3 qui peut avoir un groupe phényle ou analogue ; R5 et R6 sont identiques ou différents l'un de l'autre et représentent indépendamment un groupe alkyle en C1-C3 qui peut avoir un groupe phényle ; et Ar3 représente un groupe quinolyle qui peut avoir un substituant).
PCT/JP2014/064204 2013-05-27 2014-05-22 Procédé de production de composé isoxazoline optiquement actif WO2014192841A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015122508A1 (fr) * 2014-02-14 2015-08-20 住友化学株式会社 Procédé de fabrication d'un composé isoxazoline

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005000803A2 (fr) * 2003-06-30 2005-01-06 Sumitomo Chemical Co Compose d'uree asymetrique et procede pour produire un compose asymetrique par reaction d'addition de conjugue asymetrique avec ledit compose comme catalyseur
WO2009063910A1 (fr) * 2007-11-12 2009-05-22 Nissan Chemical Industries, Ltd. Procédé de synthèse catalytique asymétrique d'un composé d'isoxazoline optiquement actif
WO2013069731A1 (fr) * 2011-11-08 2013-05-16 日産化学工業株式会社 Procédé de synthèse asymétrique catalytique de composé isoxazoline optiquement actif et composé isoxazoline optiquement actif

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005000803A2 (fr) * 2003-06-30 2005-01-06 Sumitomo Chemical Co Compose d'uree asymetrique et procede pour produire un compose asymetrique par reaction d'addition de conjugue asymetrique avec ledit compose comme catalyseur
WO2009063910A1 (fr) * 2007-11-12 2009-05-22 Nissan Chemical Industries, Ltd. Procédé de synthèse catalytique asymétrique d'un composé d'isoxazoline optiquement actif
WO2013069731A1 (fr) * 2011-11-08 2013-05-16 日産化学工業株式会社 Procédé de synthèse asymétrique catalytique de composé isoxazoline optiquement actif et composé isoxazoline optiquement actif

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CHANDRA BHUSHAN TRIPATHI ET AL.: "Catalytic Asymmetirc Synthesis of alpha,beta-Disubstituted alpha,gamma-Diaminophosphonic Acid Precursors by Michael Addition of alpha-Substituted Nitrophosphonates to Nitroolefins", ORGANIC LETTERS, vol. 14, no. 13, 2012, pages 3296 - 3299 *
KAZUTAKA MATOBA ET AL.: "Enantioselective Synthesis of Trifluoromethyl-Substituted 2-Isoxazolines: Asymmetirc Hydroxylamine/Enone Cascade Reaction", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 49, 2010, pages 5762 - 5766, XP055003070, DOI: doi:10.1002/anie.201002065 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015122508A1 (fr) * 2014-02-14 2015-08-20 住友化学株式会社 Procédé de fabrication d'un composé isoxazoline

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