WO2014117452A1 - Synthèse et application de sel interne de phosphore de difluoro méthylène - Google Patents

Synthèse et application de sel interne de phosphore de difluoro méthylène Download PDF

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Publication number
WO2014117452A1
WO2014117452A1 PCT/CN2013/075347 CN2013075347W WO2014117452A1 WO 2014117452 A1 WO2014117452 A1 WO 2014117452A1 CN 2013075347 W CN2013075347 W CN 2013075347W WO 2014117452 A1 WO2014117452 A1 WO 2014117452A1
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group
substituted
unsubstituted
compound
formula
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PCT/CN2013/075347
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English (en)
Chinese (zh)
Inventor
肖吉昌
郑剑
蔡吉
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中国科学院上海有机化学研究所
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Publication of WO2014117452A1 publication Critical patent/WO2014117452A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5407—Acyclic saturated phosphonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles 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 in position 2
    • C07D277/70—Sulfur atoms
    • C07D277/74—Sulfur atoms substituted by carbon 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/54—Quaternary phosphonium compounds
    • C07F9/5442—Aromatic phosphonium compounds (P-C aromatic linkage)

Definitions

  • the invention relates to the field of organic synthesis, in particular, the invention provides a novel difluoromethylene scale salt and a synthesis method thereof, and the application of the compound in the production of difluorocarbene and difluoroalkenylation reaction, etc. . Background technique
  • RR 2 and R 3 are each independently selected from the group consisting of substituted or unsubstituted C1 to C20 alkyl, substituted or unsubstituted C3 to C20 cyclodecyl, substituted or unsubstituted C 1 to C 30 aryl Or a heteroaryl group, a substituted or unsubstituted benzyl group, a substituted or unsubstituted C1 ⁇ C30 decyloxy group, a substituted or unsubstituted C1 ⁇ C30 aryloxy group a substituted, unsubstituted or substituted C1 to C30 diarylamino group, a substituted or unsubstituted C1 to C30 diarylamine group, or a combination thereof;
  • the one or more hydrogen atoms on the substituent group are substituted with a substituent selected from the group consisting of: C1 ⁇ C20 fluorenyl, C3 ⁇ C10 cyclodecyl, halogen, hydroxy, carboxyl, aldehyde, acyl And an amino group;
  • the phenyl group comprises an unsubstituted phenyl group or a substituted phenyl group having 1 to 3 substituents selected from the group consisting of halogen, C1-C20 fluorenyl, OH, nitro.
  • the compound of the formula A has a purity of 30% by weight, preferably 50% by weight, more preferably 70% by weight, most preferably 99% by weight.
  • X is a leaving group, preferably selected from the group consisting of: Cl, Br, I, -OTf, -OTs, -OMs, or a combination thereof;
  • M is an alkali metal or alkaline earth metal cation and/or ammonium ion, preferably selected from the group consisting of Li, Na, K, Rb, Cs, Mg, Ca, Sr, Ba, Al, NH 4 ;
  • the solvent is a polar solvent.
  • the polar solvent includes, but is not limited to: water, methanol, ethanol, propanol, isopropanol, tert-butanol, diethyl ether, diphenyl ether, diethylene glycol dimethyl ether , petroleum ether, acetonitrile, benzonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, hexamethylphosphoric triamide, two Methyl sulfoxide, sulfolane, 1,4-dioxane, tetrahydrofuran, ethyl acetate, methyl benzoate, methylene chloride, trichloromethane or a combination thereof; preferably, the solvent is selected from the group consisting of Lower group: water, dimethyl sulfoxide, hydrazine, hydrazine-dimethylformamide, or a combination thereof.
  • the said "substantially free” means the percentage in the reaction system
  • the reaction temperature is -20 to 150 ° C, preferably -10 to 120 ° C, more preferably 10 to 100 ° C.
  • the reaction is carried out under conditions of removal of water and oxygen.
  • reaction is carried out without removing water and removing oxygen.
  • the molar ratio of the compound of the formula B to the compound of the formula C is 0.1 to 10:
  • X is a leaving group, preferably selected from the group consisting of: Cl, Br, I, -OTf, -OTs, -OMs, or a combination thereof;
  • the XCF 2 CO 2 Si (R 4 R 5 R 6 ) is prepared by the following method (i) or (ii): (i) directing XCF 2 CO 2 — M + directly in concentrated sulfuric acid Acidification to XCF 2 CO 2 H, and then reacting with ClSi(R 4 R 5 R 6 ) in an inert solvent or without solvent to form XCF 2 CO 2 Si(R 4 R 5 R 6 );
  • the inert solvent is a polar solvent, preferably an organic polar solvent.
  • the polar solvent is selected from the group consisting of water, methanol, ethanol, propanol, isopropanol, tert-butanol, diethyl ether, diphenyl ether, diethylene glycol dimethyl ether, three Ethylene glycol dimethyl ether, petroleum ether, acetonitrile, benzonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone, hexamethyl Phosphorus triamine, dimethyl sulfoxide, sulfolane, 1,4-dioxane, tetrahydrofuran, ethyl acetate, methyl benzoate, dichloromethane, chloroform or a combination thereof; preferably, The solvent is selected from the group consisting of water, dimethyl sulfoxide,
  • reaction is carried out under conditions of removal of water and oxygen.
  • reaction is carried out without removing water and removing oxygen.
  • reaction is carried out under reduced pressure, normal pressure or pressurized conditions.
  • reaction time is > 0.5 h.
  • the molar ratio of the compound XCF 2 CO 2 Si(R 4 R 5 R 6 ) to the compound ( ⁇ 3 ) ⁇ is 0.1 to 10: 0.8 to 1.2.
  • the production of the difluorocarbene comprises the steps of:
  • a process for the preparation of a compound of formula I comprising the steps of: reacting a compound of formula la with a compound of formula A according to the first aspect of the invention in an inert solvent; La AI
  • the inert solvent is an aprotic solvent, preferably an organic solvent. More preferably, the solvent includes, but is not limited to, the following groups: diethyl ether, diphenyl ether, diethylene glycol Alcohol dimethyl ether, triethylene glycol dimethyl ether, petroleum ether, acetonitrile, benzonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, methyl-2-pyrrolidone , hexamethylphosphoric triamide, dimethyl sulfoxide, sulfolane, 1,4-dioxane, tetrahydrofuran, ethyl acetate, methyl benzoate, amyl pentane, hexamidine, octyl, benzene, toluene, Xylene, chlorobenzene, dichlorobenzene, methylene chloride, trichloromethane, carbon tetrachloride
  • reaction is carried out under conditions of removal of water and oxygen. In another preferred embodiment, the reaction is carried out without removing water and removing oxygen.
  • reaction time is > 0.5 h.
  • a compound according to the first aspect of the invention which is used as a difluoroalkenylating agent for the preparation of a structure of a di-difluoroolefin compound:
  • reaction temperature is 20 to 200 °C.
  • reaction is carried out under reduced pressure, normal pressure or pressurized conditions.
  • the hydrazine compound undergoes a decarboxylation reaction under heating to form a difluorosubstituted wittig reagent in situ, which is then reacted with a compound of formula IVa to form a compound of formula IV.
  • a compound of the formula (a) for use as a difluorocarbene reagent; (b) as a difluoroalkenylation reagent; or (c) for in situ A difluoro substituted wittig reagent is produced.
  • the compound of formula A is used to introduce a difluoro-substituted fluorenyl group in the molecule of the compound. In another preferred embodiment, the compound of formula A is used to prepare difluorocyclopropene and its derivatives.
  • the compound of formula A is used to prepare a compound having a difluoromethyl group and/or a difluoromethylene group.
  • a process for the preparation of a difluoroalkenylating agent which is produced by the compound of the formula A according to the first aspect of the invention.
  • the difluoroalkenylation reagent is used to prepare a difluoroolefin.
  • the difluoroalkenylation reagent is used to introduce a vinylidene fluoride group into the molecule.
  • the difluoroalkenylating agent is a wittig reagent.
  • the difluoroalkenylating agent is produced by heating a compound of formula A. It is to be understood that within the scope of the present invention, the various technical features of the present invention and the technical features specifically described hereinafter (as in the embodiments) may be combined with each other to constitute a new or preferred technical solution. Due to space limitations, we will not repeat them here. detailed description
  • the difluorocarbene reagent provided by the invention has mild reaction conditions, simple operation, no toxicity, no additional alkali addition, and some reactions of difluorocarbene, such as difluorocyclopropionation, difluorocyclopropene, and difluorocarbazone. It has a wide range of application values in reactions such as basicization.
  • said RR 2 , R 3 are each independently selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted straight or branched butyl.
  • M is a cation, preferably an alkali metal or alkaline earth metal cation and/or an ammonium ion, including but not limited to Li, Na, K, Rb, Cs, Mg, Ca, Sr, Ba, Al, ammonium ions;
  • R 4 , R 5 and R 6 are each independently selected from substituted or unsubstituted C1 to C20 alkyl, substituted or unsubstituted C3 to C20 cyclodecyl, substituted or unsubstituted C1 to C30 aryl or heteroaryl.
  • the compound of the formula A can be used directly as a difluorocarbene reagent or can be thermally decomposed to produce a difluorocarbene.
  • the difluorocarbene reagent or difluorocarbene can be used to introduce a difluoro-substituted thiol group into a compound molecule, or to prepare a compound having a difluoro-substituted fluorenyl group.
  • the reaction temperature is 20 to 200 °C.
  • the reaction time is not particularly limited and is usually from 0.1 to 72 hours, preferably from 0.5 to 24 hours.
  • the ratio of the reactant is not particularly limited.
  • the molar ratio of the compound of the formula la to the compound of the formula A is 0.1 to 10: 0.8 to 1.2; preferably 0.2 to 6: 0.9 to 1.1.
  • the reaction temperature is 20 to 200 °C.
  • triphenyldifluoromethylene scale salt 178 mg, 0.5 ⁇ ol
  • 4- styrene 45. lmg, 0.25 mmol
  • triphenyldifluoromethylene scale salt (0.57 g, 1.6 ⁇ ol) and trifluoromethyl acetophenone (139. 3 mg, 0.8 mmol) were dissolved in two In methyl sulfoxide, the tube was sealed at 80 ° C for 4 h. Then, the heating is stopped. After the reaction is cooled, the system is extracted with water and ethyl acetate, and the mixture is separated.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne la synthèse et l'application de sel interne de phosphore de difluoro méthylène, le composé ayant la structure montrée dans la formule A : (R1R2R3)P+CF2CO2 -. Les définitions des groupes substituants sont décrites dans la spécification. La présente invention concerne également un procédé de préparation de difluorocarbène et un procédé de difluoro alcénylation. Le composé dans la formule A est utilisé comme réactif de difluorocarbène et réactif de difluoro alcénylation, et au cours de la synthèse, un alkyle à substitution difluoro ou un alcényle à substitution difluoro est introduit dans les molécules. La condition de la réaction du sel interne de phosphore et de difluoro méthylène comme réactif est modérée, le rendement de la production est élevé et l'application est large.
PCT/CN2013/075347 2013-02-04 2013-05-08 Synthèse et application de sel interne de phosphore de difluoro méthylène WO2014117452A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201310044275.0A CN103965242B (zh) 2013-02-04 2013-02-04 新型二氟亚甲基鏻内盐的合成及其应用
CN201310044275.0 2013-02-04

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105481752A (zh) * 2015-12-16 2016-04-13 四川理工学院 一种3-氟烯基氧化吲哚-螺-3,3’-三氟甲基氧化吲哚类化合物的制备方法

Families Citing this family (5)

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Publication number Priority date Publication date Assignee Title
CN105566435B (zh) * 2014-10-11 2017-12-19 中国科学院上海有机化学研究所 一种齐墩果酸衍生物及其制备方法和用途
CN106146556B (zh) * 2015-06-29 2018-09-21 中国科学院上海有机化学研究所 二氟甲基鏻盐及其制备方法和应用
CN106831599B (zh) * 2017-03-03 2019-08-23 南京理工大学 一种合成1-二氟甲基咪唑及其衍生物的方法
CN113636996A (zh) * 2021-09-02 2021-11-12 重庆大学 一种合成4-二氟甲氧基取代的香豆素化合物的方法
CN115043704B (zh) * 2022-07-26 2023-11-21 四川大学 一种高光学纯偕二氟环丙烷、制备方法及应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101538186A (zh) * 2009-04-24 2009-09-23 中国科学院上海有机化学研究所 一种制备含二氟亚甲基化合物的方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101538196A (zh) * 2008-03-18 2009-09-23 中国石油化工集团公司 一种制备2-(1-环己烯基)环己酮的方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101538186A (zh) * 2009-04-24 2009-09-23 中国科学院上海有机化学研究所 一种制备含二氟亚甲基化合物的方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BHADURY, P.S. ET AL.: "Fluorinated phosphonium ylides: versatile in situ Wittig intermediates in the synthesis of hydrofluorocarbons", JOURNAL OF FLUORINE CHEMISTRY, vol. 116, no. 1, July 2002 (2002-07-01), pages 75 - 80 *
HERKES, F.E. ET AL.: "Fluoro Olefins. I. The Synthesis of ß-Substituted Perfluoro Olefins", THE JOURNAL OF ORGANIC CHEMISTRY, vol. 32, no. 5, 1967, pages 1311 - 1318 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105481752A (zh) * 2015-12-16 2016-04-13 四川理工学院 一种3-氟烯基氧化吲哚-螺-3,3’-三氟甲基氧化吲哚类化合物的制备方法

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CN103965242B (zh) 2017-12-19

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