WO2017133283A1 - 一种复合催化剂及其应用 - Google Patents

一种复合催化剂及其应用 Download PDF

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WO2017133283A1
WO2017133283A1 PCT/CN2016/104375 CN2016104375W WO2017133283A1 WO 2017133283 A1 WO2017133283 A1 WO 2017133283A1 CN 2016104375 W CN2016104375 W CN 2016104375W WO 2017133283 A1 WO2017133283 A1 WO 2017133283A1
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compound
composite catalyst
metal
acetonitrile
salt
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PCT/CN2016/104375
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English (en)
French (fr)
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侯伟
刘彬龙
赵亚军
朱丹
张蒨
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帕潘纳(北京)科技有限公司
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/18—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms
    • B01J31/1805—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes containing nitrogen, phosphorus, arsenic or antimony as complexing atoms, e.g. in pyridine ligands, or in resonance therewith, e.g. in isocyanide ligands C=N-R or as complexed central atoms the ligands containing nitrogen
    • B01J31/181—Cyclic ligands, including e.g. non-condensed polycyclic ligands, comprising at least one complexing nitrogen atom as ring member, e.g. pyridine
    • B01J31/1825—Ligands comprising condensed ring systems, e.g. acridine, carbazole
    • B01J31/183—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline
    • B01J31/1835—Ligands comprising condensed ring systems, e.g. acridine, carbazole with more than one complexing nitrogen atom, e.g. phenanthroline comprising aliphatic or saturated rings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
    • B01J31/22—Organic complexes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
    • B01J31/28—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24 of the platinum group metals, iron group metals or copper
    • B01J31/30—Halides
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/26—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24
    • B01J31/32—Catalysts comprising hydrides, coordination complexes or organic compounds containing in addition, inorganic metal compounds not provided for in groups B01J31/02 - B01J31/24 of manganese, technetium or rhenium
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4288—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using O nucleophiles, e.g. alcohols, carboxylates, esters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0238—Complexes comprising multidentate ligands, i.e. more than 2 ionic or coordinative bonds from the central metal to the ligand, the latter having at least two donor atoms, e.g. N, O, S, P
    • B01J2531/0241—Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
    • B01J2531/16—Copper
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
    • B01J2531/70—Complexes comprising metals of Group VII (VIIB) as the central metal
    • B01J2531/72—Manganese
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Definitions

  • the invention relates to the field of catalysts, in particular to a novel composite catalyst and its use in synthesizing asymmetric 4,6-bisaryloxypyrimidine derivatives.
  • Asymmetric 4,6-bisaryloxypyrimidine derivatives are widely used as a class of high-efficiency, broad-spectrum fungicides for the prevention and treatment of a variety of plant diseases.
  • the prior art discloses a process for preparing azoxystrobin using a copper halide as a catalyst; the method is (E)-2-[2-(6-chloropyrimidin-4-yloxy)phenyl]- Methyl 3-methoxyacrylate and salicylonitrile, potassium carbonate with copper halide as catalyst, etherification reaction in polar solvent, especially N,N-dimethylformamide, after filtration, desalting The mixture is washed with N,N-dimethylformamide, and the filtrate and the washing liquid are combined under reduced pressure to remove the solvent to obtain a crude product. The crude product is crystallized from methanol and dried to give a product.
  • the copper salt catalyst has low catalytic efficiency.
  • Patent document WO0172719 discloses the preparation of asymmetric 4,6-bisaryloxypyrimidine derivatives in the presence of 2-40 mol% of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst, in particular It is a method of fluoxastrobin.
  • DABCO 1,4-diazabicyclo[2.2.2]octane
  • the method is to add (E)-5,6-dihydro-1,4,2-dioxazin-3-yl-(2-hydroxyphenyl)methanone 0-methyloxime with potassium carbonate and DABCO to A
  • an etherification reaction is carried out by mixing with 4-chloro-6-(2-chlorophenoxy)-5-fluoropyrimidine at 80 ° C, and a product is obtained by conventional post-treatment.
  • patent document WO2008043978 discloses the substrate (E)-2-[2-(6) in the presence of 0.1-2 mol% of 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst.
  • DABCO 1,4-diazabicyclo[2.2.2]octane
  • Methyl-chloropyrimidin-4-yloxy)phenyl]-3-methoxyacrylate is etherified with salicylic nitrile or a salt thereof to give the product azoxystrobin.
  • the prior art also discloses the purpose of preparing azoxystrobin by using 1,4-diazabicyclo[2.2.2]octane fixedly attached to the surface of the silica gel by a derivatization reaction to achieve catalytic etherification reaction and recovery of the catalyst.
  • the catalyst is prepared by suspending silica gel in toluene, adding 3-chloropropyltrimethoxysilane under reflux with heating, refluxing, cooling, filtering, washing, and drying, and the obtained solid is further mixed with 2-hydroxymethyl-1.
  • the present invention overcomes the deficiencies of the prior art and provides an environmentally friendly, easily recoverable catalyst which is effective for catalyzing the synthesis of asymmetric 4,6-bisaryloxypyrimidine derivatives.
  • the present invention provides a composite catalyst comprising a compound A or/and a salt thereof and a metal compound W; the compound A having the structure represented by the formula I:
  • R 1 , R 3 , R 5 and R 6 each independently represent hydrogen, halogen, C1-C10 oxygen-containing or oxygen-free aliphatic hydrocarbon group, aryl group or ester group;
  • R 2 , R 4 Each independently represents hydrogen, halogen, C1-C10 oxygen-containing or oxygen-free aliphatic hydrocarbon or aryl groups.
  • the compound A or/and its salt of the present invention may be a compound A monomer, a salt of the compound A or a mixture of the monomer and a salt.
  • the salt of the compound A is preferably one or more of the acid salt of the compound A, the alkyl quaternary ammonium salt, and the aryl quaternary ammonium salt.
  • the compound A may preferably be 1,4-diazabicyclo[2,2,2]octane or/and 2-methyl-1,4-diazabicyclo[2.2.2]octane.
  • the compound A or/and its salt of the present invention and the metal compound W are compounded in the form of A m W n . Since the compound A contains a plurality of nitrogen atoms, it can be combined with the metal compound W in various molar ratios. Therefore, in the preparation process, the composite catalyst AW obtained by the present invention may be compounded from the compound A and the metal compound W in a single molar ratio, or may be a compound in which the compound A and the metal compound W are compounded in various molar ratios. a mixture; or a mixture of various mixtures of Compound A and various mixtures of metal compounds W in a plurality of molar ratios.
  • the present invention optimizes the ratio of the compound A and the metal compound W by a large number of experiments to improve the efficiency of the catalytic reaction.
  • the molar ratio m:n of A to W may be 1 to 2:1, or may be 1:1 to 2, and preferably 1:1, that is, the compound A and the metal compound W are equimolar.
  • the metal compound W is one or more of a metal halide, an acid metal, a basic metal, an alkyl metal or an aryl metal, and a hydrate thereof; preferably a metal halide.
  • the metal is copper, manganese, cobalt, nickel, palladium, iron, aluminum or zinc; preferably copper or manganese.
  • the metal compound W is copper chloride, copper iodide, cuprous chloride, cuprous iodide or manganese chloride, and more preferably cuprous chloride, cupric chloride or manganese chloride. Most preferred is copper chloride or manganese chloride.
  • the composite catalyst of the present invention is prepared by a method comprising the steps of: taking a metal compound W, adding it to a diluent, adding a dilution of the compound A while stirring, fully reacting, filtering, washing, and drying. , that is, the composite catalyst AW;
  • the diluent and the solvent used to prepare the diluent are one or more of water, ethers, lipids, ketones, aromatics, amides, sulfones or halogenated hydrocarbons; preferably N, N-dimethylformamide or acetonitrile or butyl acetate or methyl isobutyl ketone; further preferably acetonitrile.
  • the diluent refers to a solution, suspension or a mixture of the two prepared using the diluent.
  • the invention has found through a large number of experiments that in a plurality of organic solvents, acetonitrile is used as a diluent, and the prepared composite catalyst can be obtained with high yield, and is applied to the synthesis of asymmetric 4,6-bisaryloxypyrimidine derivatives. It has high catalytic activity and stability during the reaction.
  • the preparation process is preferably carried out at normal temperature and normal pressure.
  • the composite catalyst is prepared by the following steps: preparing a copper chloride acetonitrile dilution solution, and adding 1,4-diazabicyclo ring under stirring at normal temperature and pressure [2.2.2] A acetonitrile dilution of octane was added to the molar ratio of the 1,4-diazabicyclo[2.2.2]octane to copper chloride of 1:1, and the reaction was continued for 1 hour, filtered, and washed with acetonitrile. Dry, that is.
  • the composite catalyst is prepared by the following steps: preparing a cuprous chloride acetonitrile diluent, adding 1,4-diazabicyclo ring under stirring at normal temperature and pressure [2.2.2] a acetonitrile dilution of octane, after the molar ratio of the 1,4-diazabicyclo[2.2.2]octane to cuprous chloride is 1:1, the reaction is continued for 1 h, filtered, and acetonitrile is used. Wash, dry, and get.
  • the composite catalyst is prepared by preparing a copper chloride acetonitrile dilution solution, and adding 2-methyl-1,4-diazabicyclo ring under stirring at normal temperature and normal pressure. [2.2.2] an acetonitrile dilution of octane, after adding a molar ratio of the 2-methyl-1,4-diazabicyclo[2.2.2]octane to copper chloride of 1:1, The reaction was continued for 1 h, filtered, washed with acetonitrile and dried to give.
  • the composite catalyst is prepared by the following steps: preparing a cuprous chloride acetonitrile dilution solution, and adding 2-methyl-1,4-diaza two groups under stirring at normal temperature and pressure. a acetonitrile dilution of cyclo[2.2.2]octane added to the 2-methyl group After the molar ratio of 1,4-diazabicyclo[2.2.2]octane to cuprous chloride is 1:1, the reaction is continued for 1 h, filtered, washed with acetonitrile and dried to give.
  • the composite catalyst is prepared by the following steps: preparing a dilution solution of manganese chloride in acetonitrile, and adding 1,4-diazabicyclo ring under stirring at normal temperature and normal pressure [2.2.2] An acetonitrile dilution of octane is added to the molar ratio of the 2-methyl-1,4-diazabicyclo[2.2.2]octane to cuprous chloride to 1:1, and the reaction is continued for 1 h. It is filtered, washed with acetonitrile and dried to obtain.
  • the composite catalyst is prepared by the following steps: preparing a diluted solution of manganese chloride in acetonitrile, and adding 2-methyl-1,4-diazabicyclo ring under stirring at normal temperature and normal pressure. [2.2.2] acetonitrile dilution of octane, after adding to the molar ratio of the 2-methyl-1,4-diazabicyclo[2.2.2] octane to cuprous chloride is 1:1 The reaction was continued for 1 h, filtered, washed with acetonitrile and dried to give.
  • the present invention also finds an excellent use of the composite catalyst AW in the synthesis of asymmetric 4,6-bisaryloxypyrimidine derivatives.
  • the asymmetric 4,6-bisaryloxypyrimidine derivative preferably has the structure shown in Formula II:
  • G 1 represents hydrogen or halogen
  • G 3 represents halogen or cyano
  • G 2 represents (wherein the asterisk represents the position at which the substituent binds to the mother nucleus), that is, G 2 represents (E)-5,6-dihydro-1,4,2-dioxazin-3-yl-methanone-0- Methyl hydrazine, methyl (E)-2-(3-methoxy) acrylate or methyl 2-(3,3-dimethoxy)propionate.
  • the asymmetric 4,6-bisaryloxypyrimidine derivative is further preferably azoxystrobin or/and fluoxastrobin.
  • the composite catalyst AW is a composite of a compound A or/and a salt thereof and a metal compound W; the compound A has a structure represented by the formula I:
  • R 1 , R 3 , R 5 and R 6 each independently represent hydrogen, halogen, C1-C10 oxygen-containing or oxygen-free aliphatic hydrocarbon group, aryl group or ester group;
  • R 2 , R 4 Each independently represents hydrogen, a halogen, a C1-C10 oxygen-containing or oxygen-free aliphatic hydrocarbon group or an aryl group;
  • the compound A or/and a salt thereof may be a compound A monomer, a salt of the compound A or the monomer and a mixture of salts.
  • the salt of the compound A is preferably one or more of the acid salt of the compound A, the alkyl quaternary ammonium salt, and the aryl quaternary ammonium salt.
  • the metal compound W is one or more of a metal halide, an acid metal, a basic metal, an alkyl metal or an aryl metal, and a hydrate thereof, wherein the metal is copper, manganese, cobalt, nickel , palladium, iron, aluminum or zinc.
  • the compound A or/and a salt thereof is compounded with the metal compound W in the form of A m W n , wherein the molar ratio of A to W m: n is 1 to 2:1 or 1:1 to 2, preferably 1:1.
  • the preferred embodiment of the composite catalyst AW is the same as the preferred embodiment of the composite catalyst product of the present invention.
  • the catalyst during the catalytic reaction is most preferably 1,4-diazabicyclo[2.2.2]octane or 2-methyl.
  • the base-1,4-diazabicyclo[2.2.2]octane is compounded with copper chloride or manganese chloride in a molar ratio of 1:1.
  • the synthetic route of the asymmetric 4,6-bisaryloxypyrimidine derivative is:
  • G 1, G 2, G 3 groups in the formula of the present invention is represented by II, refer to the same;
  • the amount of the composite catalyst AW is 0.1 of the compound 1. ⁇ 50 mol%;
  • the above reaction can be carried out stepwise or in a one-pot process.
  • the solvent for the reaction is one or more of an ether, a lipid, a ketone, an aromatic, an amide, a sulfone or a halogenated hydrocarbon, preferably N,N-dimethylformamide or acetonitrile or Butyl acetate or methyl isobutyl ketone is further preferably acetonitrile.
  • acetonitrile can be used as a solvent to make the composite catalyst work efficiently and stably. In the reaction system of acetonitrile, the composite catalyst remains after recovery. Can maintain high catalytic efficiency.
  • the reaction temperature is 10 to 180 ° C, preferably 30 to 120 ° C, more preferably 60 to 80 ° C; and the reaction is preferably carried out under normal pressure.
  • the synthetic route of the asymmetric 4,6-bisaryloxypyrimidine derivative is:
  • G 1 , G 2 , G 3 is the same as the formula of the general formula II of the present invention.
  • the amount of the composite catalyst AW is 0.1 of the compound 1. ⁇ 50 mol%;
  • the above reaction can be carried out stepwise or in a one-pot process.
  • the solvent for the reaction is one or more of an ether, a lipid, a ketone, an aromatic, an amide, a sulfone or a halogenated hydrocarbon, preferably N,N-dimethylformamide or acetonitrile or Butyl acetate or methyl isobutyl ketone is further preferably acetonitrile.
  • acetonitrile can be used as a solvent to make the composite catalyst work efficiently and stably. In the reaction system of acetonitrile, the composite catalyst remains after recovery. Can maintain high catalytic efficiency.
  • the reaction temperature is 10 to 180 ° C, preferably 30 to 120 ° C, more preferably 60 to 80 ° C; and the reaction is preferably carried out under normal pressure.
  • the composite catalyst AW can be recovered by the following methods: after the reaction is terminated, the water layer is separated by desolvation, acidification and extraction, and the pH of the aqueous layer is adjusted. The value is 4 to 8, preferably pH 6, and a solid is precipitated, filtered, and dried to obtain a recovered catalyst.
  • the composite catalyst provided by the invention can efficiently catalyze the synthesis reaction of asymmetric 4,6-bisaryloxypyrimidine derivatives, and can be recycled and reused by a simple method, thereby reducing catalyst consumption, avoiding environmental pollution, and adapting to large scale. Industrial production.
  • the present embodiment provides a preparation method of the composite catalyst AW, specifically: adding 10 g (99%, 0.101 mol) of cuprous chloride, 30 ml of N,N-dimethylformamide in a 100 ml three-necked flask, and stirring at room temperature. Add 30 mL of a solution of 11.3 g (98%, 0.101 mol) of 1,4-diazabicyclo[2,2,2]octane in N,N-dimethylformamide. After the addition, the reaction was continued for 1 h and filtered. The solid was washed twice with 40 ml of N,N-dimethylformamide, and dried solid to give 19.2 g of red-brown product, i.e., composite catalyst AW1, yield 90%.
  • Example 2 Compared with Example 1, the only difference is that copper chloride is replaced by 19.23 g (99.5%, 0.101 mol) of cuprous iodide, and 1,4-diazabicyclo[2,2,2] octane The alkane was replaced with an equimolar amount of 1,4-diazabicyclo[2,2,2]octane hydrochloride to give 27.8 g of a light green solid, i.e., composite catalyst AW2, yield 90%.
  • the cuprous chloride is replaced by an equimolar amount of manganese chloride (optional manganese chloride tetrahydrate) to obtain 27.8 g of a dark brown solid product, that is, a composite catalyst AW3, yield. 89%.
  • Example 2 Compared with Example 1, the only difference is that copper chloride was replaced by copper chloride 13.5 g (98%, 0.101 mol), and N,N-dimethylformamide was replaced with acetonitrile to obtain 23.1 g red. A brown solid product, the composite catalyst AW4, yield 93%.
  • Example 2 Compared with Example 1, the only difference is that 1,4-diazabicyclo[2,2,2]octane is replaced by an equimolar number of 2-methyl-1,4-diazabicyclo ring. [2.2.2] Octane, and N,N-dimethylformamide was replaced with acetonitrile to obtain 20.67 g of a yellow-green solid product, that is, a composite catalyst AW5, yield 91%.
  • Example 2 Compared with Example 1, the only difference is that copper chloride is replaced by an equimolar amount of copper chloride, and 1,4-diazabicyclo[2,2,2]octane is replaced by an equimolar number. 2-methyl-1,4-diazabicyclo[2.2.2]octane, and N,N-dimethylformamide was replaced by acetonitrile to give 24.74 g of a reddish brown solid product, ie, composite catalyst AW6 The yield was 94%.
  • the composite catalyst AW1 obtained in Example 1 was 0.2 g (0.95 mmol), and stirring was continued at this temperature for 10 minutes, followed by the addition of (E)-2-[2-(6-pyrimidin-4-yloxy)phenyl]-3-methoxy Methyl acrylate 10g (95%, 31.18mmol), heated to 80 ° C reaction, 2 hours after HPLC monitoring showed (E)-2-[2-(6-pyrimidin-4-yloxy)phenyl]-3-methyl
  • the methyl methacrylate content is ⁇ 0.1%, N,N-dimethylformamide is recovered by distillation under reduced pressure, and 30 ml of toluene is added to the distillation residue, followed by the addition of 40 ml of a 5 mol/L aqueous hydrochloric acid solution, and the mixture is at 80 ° C.
  • Example 8 Compared with Example 8, the only difference is that the composite catalyst obtained in Example 2 is used. AW2 was substituted for AW1 to obtain 53.52 g of a toluene solution containing azoxystrobin (23.2% w/w), which was 98.9% of theory.
  • Example 8 Compared with Example 8, the only difference was that the composite catalyst AW3 obtained in Example 3 was used instead of AW1 to obtain 51.35 g of a toluene solution containing azoxystrobin (24.3% w/w), which was 99.3% of the theoretical value.
  • Example 8 Compared with Example 8, the only difference is that the composite catalyst AW4 obtained in Example 4 was used instead of AW1, and the reaction solvent N,N-dimethylformamide was replaced with acetonitrile to obtain 52.38 g of a toluene solution containing azoxystrobin. (23.9% w/w), which is 99.5% of the theoretical value.
  • Example 11 Compared with Example 11, the only difference was that potassium carbonate and salicylonitrile were not added, and potassium salt of salicylonitrile (4.89 g, 31.18 mmol) was added to obtain 50.25 g of a toluene solution containing azoxystrobin (24.7% w/). w), which is 99.1% of the theoretical value.
  • Example 8 Compared with Example 8, the only difference is that the composite catalyst AW5 obtained in Example 6 was used instead of AW1, and the reaction solvent N,N-dimethylformamide was replaced with acetonitrile to obtain 52.14 g of a toluene solution containing azoxystrobin. (24.1% w/w), which is 99.9% of the theoretical value.
  • Example 12 Compared with Example 12, the only difference was that instead of AW1, the composite catalyst AW6 obtained in Example 7 was used to obtain 53.0 g of a toluene solution containing azoxystrobin (23.7% w/w), which was 100% of the theoretical value.
  • Example 14 Following the reaction described in Example 14, the catalyst AW6' recovered in Example 18 was used in place of the catalyst AW6, and after 3.5 hours of reaction, 50.28 g of a toluene solution was obtained, containing azoxystrobin (23.6% w/w), 95.3% of theory. .
  • Example 12 The reaction was carried out in the same manner as in Example 12 except that the composite catalyst AW4 obtained in Example 4 was not added, but the potassium salt of salicylic acid was directly added to the acetonitrile suspension of the composite catalyst AW4 described in Example 5, and the subsequent operations were identical. 52.34 g of a toluene solution was obtained, containing azoxystrobin (23.9% w/w), which was 99.5% of theory.
  • Example 14 Compared with Example 14, the only difference is that during the reaction, the addition of catalyst AW6 was changed to the absence of catalyst, and after 6 hours of reaction, HPLC monitoring showed (E)-2-[2-(6-pyrimidin-4-yloxy) The remaining 15% of methyl phenyl]-3-methoxyacrylate. After the same post-treatment, 47.32 g of toluene solution was obtained, and the toluene solution was analyzed, containing azoxystrobin (17.3% w/w), theoretical value of 65.1. %.
  • Example 14 Compared with Example 14, the only difference is that in the course of the reaction, the difference is that The chemical agent AW6 was changed to copper chloride. After 6 hours of reaction, HPLC monitoring showed that 10% of (E)-2-[2-(6-pyrimidin-4-yloxy)phenyl]-3-methoxyacrylic acid methyl ester remained. After the same post-treatment, 49.58 g of a toluene solution was obtained, and the toluene solution was analyzed to contain azoxystrobin (19.2% w/w), which was 75.6% of theory.
  • Example 14 Compared with Example 14, the only difference is that copper chloride and 2-methyl-1,4-diazabicyclo[2.2.2]octane are separately added as catalysts in place of the catalyst AW6 during the reaction.
  • the molar ratio of the two was 1:1, and the total amount was 0.2 g; 55.47 g of a toluene solution was obtained, containing azoxystrobin (22.1% w/w), which was 97.5% of the theoretical value.

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Abstract

一种复合催化剂，由化合物A或/和其盐与金属化合物W复合而成，化合物A具有通式I所示结构：通式I中，R 1、R 3、R 5、R 6各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基、芳基或酯基；R 2、R 4各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基或芳基。该复合催化剂可以高效催化不对称4,6-双芳氧基嘧啶衍生物的合成反应，可以通过简单的方法回收重复使用。

Description

一种复合催化剂及其应用 技术领域
本发明涉及催化剂领域，具体涉及一种新型复合催化剂及其在合成不对称4,6-双芳氧基嘧啶衍生物中的应用。
背景技术
不对称4,6-双芳氧基嘧啶衍生物，尤其是嘧菌酯和氟嘧菌酯，作为一类高效、广谱型的杀菌剂，被广泛用于多种植物病害的预防和治疗。
现有技术公开了一种以铜的卤化物为催化剂制备嘧菌酯的方法；该方法是将(E)-2-[2-(6-氯嘧啶-4-基氧基]苯基]-3-甲氧基丙烯酸甲酯与水杨腈，碳酸钾以铜的卤化物为催化剂，在极性溶剂特别是N,N-二甲基甲酰胺中发生醚化反应，反应结束后过滤除盐并用N,N-二甲基甲酰胺进行洗涤，滤液和洗涤液合并减压蒸馏除去溶剂后得到粗产品，粗产品用甲醇结晶，干燥得到产品。该方法中铜盐催化剂催化效率低。
专利文献WO0172719公开了在2-40mol％的1，4-二氮杂二环[2.2.2]辛烷(DABCO)作为催化剂存在下制备不对称4，6-双芳氧基嘧啶衍生物，尤其是氟嘧菌酯的方法。该方法是将(E)-5，6-二氢-1，4，2-二恶嗪-3-基-(2-羟苯基)甲酮0-甲基肟与碳酸钾和DABCO加入甲基异丁酮和水的混合物中，在80℃下与4-氯-6-(2-氯苯氧基)-5-氟嘧啶混合发生醚化反应，经过常规后处理得到产品。
另外，专利文献WO2008043978公开了在0.1-2mol％的1，4-二氮杂二环[2.2.2]辛烷(DABCO)作为催化剂存在下将底物(E)-2-[2-(6-氯嘧啶-4基氧基)苯基]-3-甲氧基丙烯酸甲酯与水杨腈或其盐发生醚化反应得到产品嘧菌酯。
上述两篇公开的专利WO0172719和WO2008043978是对前述现有技术中用铜的卤化物为催化剂的合成方法的改进。然而，这些专利提供的技术方案中没有涉及对催化剂的回收，不利于实现高效、环保的生产。
现有技术还公开了制备嘧菌酯时使用1，4-二氮杂二环[2.2.2]辛烷通过衍生反应固定连接在硅胶表面，来达到催化醚化反应以及回收催化剂的目的。该催化剂的制备方法是将硅胶悬浮于甲苯中，加热回流下加入3-氯丙基三甲氧基硅烷，回流，冷却，过滤，洗涤，干燥，得到的固体再与2-羟甲基-1，4-二氮杂二环[2.2.2]辛烷以及氢化钠，在四氢呋喃中加热回流反应，冷却，过滤，洗涤，干燥才得到用以制备嘧菌酯醚化反应的催化剂，这种可回收的催化剂的制备过程相当复杂和苛刻，并且原料成本很高，因而这种催化剂不利于工业化生产之应用。
发明内容
本发明克服现有技术的缺陷，提供一种环保、易于回收的催化剂，可有效催化不对称4,6-双芳氧基嘧啶衍生物的合成反应。
具体而言，本发明提供了一种复合催化剂，由化合物A或/和其盐与金属化合物W复合而成；所述化合物A具有通式I所示结构：
Figure PCTCN2016104375-appb-000001
所述通式I中，R1、R3、R5、R6各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基、芳基或酯基；R2、R4各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基或芳基。
本发明所述化合物A或/和其盐可以是化合物A单体、化合物A的盐或所述单体与盐的混合物。所述化合物A的盐优选为化合物A的酸式盐、烷基季铵盐、芳基季铵盐中的一种或多种。
所述化合物A可优选为1,4-二氮杂二环[2,2,2]辛烷或/和2-甲基-1,4-二氮杂二环[2.2.2]辛烷。
本发明所述化合物A或/和其盐与金属化合物W以AmWn的形式复合而成。由于化合物A中含有多个氮原子，可以以多种摩尔比与金属化合物W结合。因此，在制备过程中，本发明所获得的复合催化剂AW可以由化合物A与金属化合物W以单一的摩尔比例复合而成，也可以是化合物A与金属化合物W以多种摩尔比例复合而成的混合物；或化合物A的多种混合物与金属化合物W的多种混合物以多种摩尔比例复合而成的混合物。本发明通过大量实验，对所述化合物A和金属化合物W的配比进行优选，以提高催化反应效率。其中，A与W的摩尔比m:n可以为1～2:1，也可以为1:1～2，优选为1:1，即化合物A与金属化合物W等摩尔复合。
所述金属化合物W为金属卤化物、酸式金属、碱式金属、烷基金属或芳基金属及其水合物中的一种或多种；优选为金属卤化物。其中，所述金属为铜、锰、钴、镍、钯、铁、铝或锌；优选为铜或锰。
作为本发明的优选方案，所述金属化合物W为氯化铜、碘化铜、氯化亚铜、碘化亚铜或氯化锰，进一步优选为氯化亚铜、氯化铜或氯化锰，最优选为氯化铜或氯化锰。本发明通过大量实验发现，当金属化合物选用氯化铜或氯化锰时，所得复合催化剂不仅催化活性高，且性能更加稳定，参与催化反应回收后，依然具有较好的催化活性。具体而言，本发明所述复合催化剂由包括以下步骤的方法制备而成：取金属化合物W，加入到稀释剂中，边搅拌边加入化合物A的稀释液，充分反应后，过滤、洗涤、干燥，即得复合催化剂AW；
或调整加料顺序：取化合物A，加入到稀释剂中，边搅拌边加入金属化合物W的稀释液，充分反应后，过滤、洗涤、干燥，即得复合催化剂AW。
所述稀释剂以及配制所述稀释液所用的溶剂为水、醚类、脂类、酮类、芳香族类、酰胺类、砜类或卤代烃中的一种或多种；优选为N,N-二甲基甲酰胺或乙腈或乙酸丁酯或甲基异丁基酮；进一步优选为乙腈。所述稀释液是指采用所述稀释剂配制而成的溶液、悬浮液或二者的混合形式。本发明通过大量实验发现，在众多的有机溶剂中，采用乙腈作为稀释剂，可以使制备得到的复合催化剂收率较高，应用于合成不对称4,6-双芳氧基嘧啶衍生物的催化反应时具有较高的催化活性和稳定性。
所述制备过程优选在常温、常压下进行。
作为本发明的一种优选方案，所述复合催化剂采用以下步骤制备而成：配制氯化铜的乙腈稀释液，常温常压下边搅拌边加入1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至所述1,4-二氮杂二环[2.2.2]辛烷与氯化铜的摩尔比为1:1后，继续反应1h，过滤，用乙腈洗涤，干燥，即得。
作为本发明的一种优选方案，所述复合催化剂采用以下步骤制备而成：配制氯化亚铜的乙腈稀释液，常温常压下边搅拌边加入1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至所述1,4-二氮杂二环[2.2.2]辛烷与氯化亚铜的摩尔比为1:1后，继续反应1h，过滤，用乙腈洗涤，干燥，即得。
作为本发明的一种优选方案，所述复合催化剂采用以下步骤制备而成：配制氯化铜的乙腈稀释液，常温常压下边搅拌边加入2-甲基-1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至所述2-甲基-1,4-二氮杂二环[2.2.2]辛烷与氯化铜的摩尔比为1:1后，继续反应1h，过滤，用乙腈洗涤，干燥，即得。
作为本发明的一种优选方案，所述复合催化剂采用以下步骤制备而成：配制氯化亚铜的乙腈稀释液，常温常压下边搅拌边加入2-甲基-1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至所述2-甲基 -1,4-二氮杂二环[2.2.2]辛烷与氯化亚铜的摩尔比为1:1后，继续反应1h，过滤，用乙腈洗涤，干燥，即得。
作为本发明的一种优选方案，所述复合催化剂采用以下步骤制备而成：配制氯化锰的乙腈稀释液，常温常压下边搅拌边加入1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至所述2-甲基-1,4-二氮杂二环[2.2.2]辛烷与氯化亚铜的摩尔比为1:1后，继续反应1h，过滤，用乙腈洗涤，干燥，即得。
作为本发明的一种优选方案，所述复合催化剂采用以下步骤制备而成：配制氯化锰的乙腈稀释液，常温常压下边搅拌边加入2-甲基-1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至所述2-甲基-1,4-二氮杂二环[2.2.2]辛烷与氯化亚铜的摩尔比为1:1后，继续反应1h，过滤，用乙腈洗涤，干燥，即得。
本发明同时发现复合催化剂AW在合成不对称4,6-双芳氧基嘧啶衍生物中的优异应用。所述不对称4,6-双芳氧基嘧啶衍生物优选为结构如通式II所示：
Figure PCTCN2016104375-appb-000002
所述通式II中，G1代表氢或卤素；G3代表卤素或氰基；G2代表
Figure PCTCN2016104375-appb-000003
(其中，星号代表取代基与母核结合的位置)，即G2代表(E)-5，6-二氢-1，4，2-二恶嗪-3-基-甲酮-0-甲基肟、(E)-2-(3-甲氧基)丙烯酸甲酯或2-(3,3-二甲氧基)丙酸甲酯。
所述不对称4,6-双芳氧基嘧啶衍生物进一步优选为嘧菌酯或/和氟嘧菌酯。
所述复合催化剂AW由化合物A或/和其盐与金属化合物W复合而成；所述化合物A具有通式I所示结构：
Figure PCTCN2016104375-appb-000004
所述通式I中，R1、R3、R5、R6各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基、芳基或酯基；R2、R4各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基或芳基；所述化合物A或/和其盐可以是化合物A单体、化合物A的盐或所述单体与盐的混合物。所述化合物A的盐优选为化合物A的酸式盐、烷基季铵盐、芳基季铵盐中的一种或多种。
所述金属化合物W为金属卤化物、酸式金属、碱式金属、烷基金属或芳基金属及其水合物中的一种或多种，其中，所述金属为铜、锰、钴、镍、钯、铁、铝或锌。
所述化合物A或/和其盐与金属化合物W以AmWn的形式复合而成，其中，A与W的摩尔比m:n为1～2:1或1:1～2，优选为1:1。
在应用于催化合成不对称4,6-双芳氧基嘧啶衍生物时，所述复合催化剂AW的优选方案与本发明所述复合催化剂产品的优选方案相同。为了提高对嘧菌酯或/和氟嘧菌酯的催化合成反应效率，所述催化反应过程中的催化剂最优选由1,4-二氮杂二环[2.2.2]辛烷或2-甲基-1,4-二氮杂二环[2.2.2]辛烷与氯化铜或氯化锰以摩尔比1:1复合而成。
作为本发明的一种具体方案，所述不对称4,6-双芳氧基嘧啶衍生物的合成路线为：
Figure PCTCN2016104375-appb-000005
其中，所述G1、G2、G3所代表的基团与本发明通式II的指代相同；
具体包括以下步骤：
(1)以化合物1和化合物2或化合物2的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物3；该步骤中，复合催化剂AW的用量为化合物1的0.1～50mol％；
(2)所述化合物3和化合物4或化合物4的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物5，即可；该步骤中，复合催化剂AW的用量为化合物3的0.1～50mol％。
以上反应可分步进行，也可采用一锅法进行。所述反应的溶剂为醚类、脂类、酮类、芳香族类、酰胺类、砜类或卤代烃中的一种或多种，优选为N,N-二甲基甲酰胺或乙腈或乙酸丁酯或甲基异丁基酮，进一步优选为乙腈，在众多的有机溶剂中，采用乙腈作为溶剂可以使复合催化剂高效、稳定的发挥作用，在乙腈的反应体系中，复合催化剂回收后仍然可以保持较高的催化效率。所述反应温度为10～180℃，优选为30～120℃，进一步优选为60～80℃；反应优选在常压下进行。
作为本发明的一种具体方案，所述不对称4,6-双芳氧基嘧啶衍生物的合成路线为：
Figure PCTCN2016104375-appb-000006
其中，所述G1、G2、G3所代表的基团与本发明通式II的指代相同；
具体包括以下步骤：
(1)以化合物1和化合物4或化合物4的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物6；该步骤中，复合催化剂AW的用量为化合物1的0.1～50mol％；
(2)所述化合物6和化合物2或化合物2的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物5，即可；该步骤中，复合催化剂AW的用量为化合物6的0.1～50mol％。
以上反应可分步进行，也可采用一锅法进行。所述反应的溶剂为醚类、脂类、酮类、芳香族类、酰胺类、砜类或卤代烃中的一种或多种，优选为N,N-二甲基甲酰胺或乙腈或乙酸丁酯或甲基异丁基酮，进一步优选为乙腈，在众多的有机溶剂中，采用乙腈作为溶剂可以使复合催化剂高效、稳定的发挥作用，在乙腈的反应体系中，复合催化剂回收后仍然可以保持较高的催化效率。所述反应温度为10～180℃，优选为30～120℃，进一步优选为60～80℃；反应优选在常压下进行。
所述复合催化剂AW在催化合成不对称4,6-双芳氧基嘧啶衍生物后，可采用以下方法进行回收：反应终止后，经脱溶、酸化和萃取，分离出水层，调节水层pH值至4～8，优选pH值为6，析出固体，过滤，干燥，得到回收的催化剂。
本发明提供的复合催化剂可以高效催化不对称4,6-双芳氧基嘧啶衍生物的合成反应，且可以通过简单的方法回收重复使用，减少了催化剂的消耗，避免了环境污染，适应大规模工业化生产。
具体实施方式
以下实施例用于说明本发明，但不用来限制本发明的范围。
实施例1：复合催化剂AW1的制备
本实施例提供了一种复合催化剂AW的制备方法，具体为：在100ml三口瓶中加入氯化亚铜10g(99％，0.101mol)，N,N-二甲基甲酰胺30ml，室温搅拌下加入1，4-二氮杂二环[2,2,2]辛烷11.3g(98％，0.101mol)的N,N-二甲基甲酰胺溶液30mL，加入完毕后继续反应1h，过滤，用40ml N,N-二甲基甲酰胺洗涤固体两次，固体干燥，得红褐色产品19.2g，即复合催化剂AW1，收率90％。
实施例2：复合催化剂AW2的制备
与实施例1相比，区别仅在于：将氯化亚铜替换为碘化亚铜19.23g(99.5％，0.101mol)，将1，4-二氮杂二环[2,2,2]辛烷替换为等摩尔的1，4-二氮杂二环[2,2,2]辛烷盐酸盐，得27.8g浅绿色固体，即复合催化剂AW2，收率90％。
实施例3：复合催化剂AW3的制备
与实施例1相比，区别仅在于：将氯化亚铜替换为等摩尔数的氯化锰(可选用四水合氯化锰)，得27.8g深棕色固体产物，即复合催化剂AW3，收率89％。
实施例4：复合催化剂AW4的制备
与实施例1相比，区别仅在于：将氯化亚铜替换为氯化铜13.5g(98％，0.101mol)，并将N,N-二甲基甲酰胺替换为乙腈，得23.1g红褐色固体产品，即复合催化剂AW4，收率93％。
实施例5：复合催化剂AW4的乙腈悬浮液的制备
在100ml三口瓶中加入氯化铜0.109g(99％，0.8mmol)，乙 腈10ml，室温搅拌下加入1，4-二氮杂二环[2,2,2]辛烷0.091g(98％，0.8mmol)的乙腈溶液10mL，加入完毕后继续反应1h，理论上得到含0.2g复合催化剂AW4的乙腈悬浮液20ml。
实施例6：复合催化剂AW5的制备
与实施例1相比，区别仅在于：将1，4-二氮杂二环[2,2,2]辛烷替换为等摩尔数的2‐甲基‐1,4‐二氮杂二环[2.2.2]辛烷，并将N,N-二甲基甲酰胺替换为乙腈，得20.67g黄绿色固体产品，即复合催化剂AW5，收率91％。
实施例7：复合催化剂AW6的制备
与实施例1相比，区别仅在于：将氯化亚铜替换为等摩尔数的氯化铜，将1，4-二氮杂二环[2,2,2]辛烷替换为等摩尔数的2‐甲基‐1,4‐二氮杂二环[2.2.2]辛烷，并将N,N-二甲基甲酰胺替换为乙腈，得24.74g红褐色固体产品，即复合催化剂AW6，收率94％。
实施例8：嘧菌酯的合成
在100ml三口瓶中加入20ml N,N-二甲基甲酰胺,碳酸钾5.60g(98％，40.53mmol)，水杨腈4.17g(98％，34.30mmol)，升温至60℃搅拌10min，加入实施例1所得复合催化剂AW1 0.2g(0.95mmol)，在此温度下继续搅拌10min后加入(E)-2-[2-(6-嘧啶-4-基氧]苯基]-3-甲氧基丙烯酸甲酯10g(95％，31.18mmol)，升温至80℃反应，2h后HPLC监控显示(E)-2-[2-(6-嘧啶-4-基氧]苯基]-3-甲氧基丙烯酸甲酯含量<0.1％,减压蒸馏回收N,N-二甲基甲酰胺，30ml甲苯加入到蒸馏残余物中，随后加入40ml，5mol/L的盐酸水溶液，并将混合物在80℃搅拌1h，分层，20ml甲苯萃取水相，合并有机相共51.54g，对该甲苯溶液进行分析，含有嘧菌酯(24.2％w/w)，为理论值的99.1％。
实施例9：嘧菌酯的合成
与实施例8相比，区别仅在于：用实施例2所得的复合催化剂 AW2代替AW1，得到甲苯溶液53.52g，含有嘧菌酯(23.2％w/w)，为理论值的98.9％。
实施例10：嘧菌酯的合成
与实施例8相比，区别仅在于：用实施例3所得的复合催化剂AW3代替AW1，得到甲苯溶液51.35g，含有嘧菌酯(24.3％w/w)，为理论值的99.3％。
实施例11：嘧菌酯的合成
与实施例8相比，区别仅在于：用实施例4所得的复合催化剂AW4代替AW1，并将反应溶剂N,N-二甲基甲酰胺替换为乙腈，得到甲苯溶液52.38g，含有嘧菌酯(23.9％w/w)，为理论值的99.5％。
实施例12：嘧菌酯的合成
与实施例11相比，区别仅在于：不加碳酸钾和水杨腈，加入水杨腈的钾盐(4.89g，31.18mmol)，得到甲苯溶液50.25g，含有嘧菌酯(24.7％w/w)，为理论值的99.1％。
实施例13：嘧菌酯的合成
与实施例8相比，区别仅在于：用实施例6所得的复合催化剂AW5代替AW1，并将反应溶剂N,N-二甲基甲酰胺替换为乙腈，得到甲苯溶液52.14g，含有嘧菌酯(24.1％w/w)，为理论值的99.9％。
实施例14：嘧菌酯的合成
与实施例12相比，区别仅在于：用实施例7所得的复合催化剂AW6代替AW1，得到甲苯溶液53.0g，含有嘧菌酯(23.7％w/w)，为理论值的100％。
实施例15：2-{2-[6-(2-氰基苯氧基)嘧啶-4-基氧基]苯基}-3,3-二甲氧基丙酸甲酯的合成
在100ml三口瓶中加入20ml甲基异丁基酮，碳酸钾5.09g(98％，36.85mmol)，水杨腈3.79g(98％，31.18mmol)，升温至60℃搅拌10min，加入实施例4所得复合催化剂AW4 0.2g(0.81mmol)， 在此温度下继续搅拌10min后加入2-{2-[6-氯嘧啶-4-基氧基]苯基}-3,3-二甲氧基丙酸甲酯10.53g(95％，28.35mmol)，升温至80℃反应，2h后HPLC监控显示2-{2-[6-氯嘧啶-4-基氧基]苯基}-3,3-二甲氧基丙酸甲酯含量<0.1％,减压蒸馏回收甲基异丁基酮，30ml甲苯加入到蒸馏残余物中，随后加入40ml，5mol/L的盐酸水溶液，并将混合物在80℃搅拌1h，分层，20ml甲苯萃取水相，合并有机相共51.8g，对该甲苯溶液进行分析，显示2-{2-[6-(2-氰基苯氧基)嘧啶-4-基氧基]苯基}-3,3-二甲氧基丙酸甲酯(68.8％)和嘧菌酯(29.2％)。
实施例16：2-{2-[6-(2-氰基苯氧基)嘧啶-4-基氧基]苯基}-3,3-二甲氧基丙酸甲酯的合成
在100ml三口瓶中加入20ml乙酸丁酯,碳酸钾7.76g(98％，56.12mmol)，2-(2-羟基苯基)-3,3-二甲氧基丙酸甲酯11.41g(98％，47.49mmol)，升温至60℃搅拌10min，加入实施例4所得复合催化剂AW4 0.2g(0.81mmol)，在此温度下继续搅拌10min后加入4-氯-6-(2-氰基苯氧基)嘧啶10.31g(97％，43.17mmol)，升温至80℃反应，2h后HPLC监控显示4-氯-6-(2-氰基苯氧基)嘧啶含量<0.1％,减压蒸馏回收乙酸丁酯，30ml甲苯加入到蒸馏残余物中，随后加入40ml，5mol/L的盐酸水溶液，并将混合物在80℃搅拌1h，分层，20ml甲苯萃取水相，合并有机相共51.3g，对该甲苯溶液进行分析，显示2-{2-[6-(2-氰基苯氧基)嘧啶-4-基氧基]苯基}-3,3-二甲氧基丙酸甲酯(60.5％)和嘧菌酯(38.0％)。
实施例17：氟嘧菌酯的合成
100ml三口瓶中加入(E)-5,6-二氢-1,4,2-二噁嗪-3-基-(2-羟苯基)甲酮O-甲基肟13.0g(98％，50.5mmol),碳酸钾9.0g(98％，65mmol)，乙腈60ml，升温至60℃搅拌10min，加入实施例4所得复合催化剂AW4 0.2g(0.81mmol)，再搅拌10min后，加入4-氯-6-(2-氯苯氧 基)-5-氟嘧啶12.9g(98％，49.8mmol),升温至80℃搅拌反应，2h后HPLC监控显示4-氯-6-(2-氯苯氧基)-5-氟嘧啶含量<0.05％,减压蒸馏回收乙腈，50ml甲苯加入到蒸馏残余物中，随后加入40ml，5mol/L的盐酸水溶液，并将混合物在80℃搅拌1h，分层，20ml甲苯萃取水相，合并有机相共75.3g，对此甲苯溶液进行分析，含氟嘧菌酯(28.9％w/w)，为理论值的99.3％。
实施例18：
按照实施例14所述反应，加20ml甲苯萃取后，将分离出的水层调节pH值至6，析出的固体，过滤，干燥得到0.15g回收的催化剂AW6’。
实施例19：
按照实施例14所述反应，用实施例18回收的催化剂AW6’代替催化剂AW6，且反应3.5h后，得到甲苯溶液50.28g，含有嘧菌酯(23.6％w/w)，理论值的95.3％。
实施例20：
按照实施例12所述反应，不同的是不加入实施例4所得的复合催化剂AW4而是直接向实施例5所述的复合催化剂AW4的乙腈悬浮液中加入水杨腈的钾盐，后续操作一致，得到甲苯溶液52.34g，含有嘧菌酯(23.9％w/w)，为理论值的99.5％。
对比例1
与实施例14相比，区别仅在于：在反应过程中将加入催化剂AW6改为不加入催化剂，反应6h后HPLC监控显示(E)-2-[2-(6-嘧啶-4-基氧]苯基]-3-甲氧基丙烯酸甲酯剩余15％。经过相同的后处理得到47.32g甲苯溶液，对该甲苯溶液进行分析，含有嘧菌酯(17.3％w/w)，理论值的65.1％。
对比例2
与实施例14相比，区别仅在于：在反应过程中不同的是将催 化剂AW6改为氯化铜，反应6h后HPLC监控显示(E)-2-[2-(6-嘧啶-4-基氧]苯基]-3-甲氧基丙烯酸甲酯剩余10％。经过相同的后处理得到49.58g甲苯溶液，对该甲苯溶液进行分析，含有嘧菌酯(19.2％w/w)，为理论值的75.6％。
对比例3
与实施例14相比，区别仅在于：在反应过程中分别添加氯化铜和2-甲基-1,4-二氮杂二环[2.2.2]辛烷作为催化剂代替所述催化剂AW6，二者的摩尔比为1:1，总量为0.2g；得到甲苯溶液55.47g，含有嘧菌酯(22.1％w/w)，为理论值的97.5％。
虽然，上文中已经用一般性说明、具体实施方式及试验，对本发明作了详尽的描述，但在本发明基础上，可以对之作一些修改或改进，这对本领域技术人员而言是显而易见的。因此，在不偏离本发明精神的基础上所做的这些修改或改进，均属于本发明要求保护的范围。

Claims (10)

  1. 一种复合催化剂，其特征在于，由化合物A或/和其盐与金属化合物W复合而成；所述化合物A具有通式I所示结构：
    Figure PCTCN2016104375-appb-100001
    所述通式I中，R1、R3、R5、R6各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基、芳基或酯基；R2、R4各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基或芳基；
    所述金属化合物W为金属卤化物、酸式金属、碱式金属、烷基金属或芳基金属及其水合物中的一种或多种，其中，所述金属为铜、锰、钴、镍、钯、铁、铝或锌。
  2. 根据权利要求1所述的复合催化剂，其特征在于，所述化合物A或/和其盐与金属化合物W以AmWn的形式复合而成；
    其中，A与W的摩尔比m:n为1～2:1或1:1～2，优选为1:1。
  3. 根据权利要求1或2所述的复合催化剂，其特征在于，所述化合物A为1,4-二氮杂二环[2.2.2]辛烷、2-甲基-1,4-二氮杂二环[2.2.2]辛烷中的一种或两种；
    所述金属化合物W为氯化亚铜CuCl、氯化铜CuCl2、氯化锰MnCl2中的一种或多种。
  4. 根据权利要求1～3任意一项所述的复合催化剂，其特征在于，由包括以下步骤的方法制备而成：取金属化合物W，加入到稀释剂中，边搅拌边加入化合物A或/和其盐的稀释液，充分反应后，过滤、洗涤、干燥，即得复合催化剂AW；
    或，取化合物A或/和其盐，加入到稀释剂中，边搅拌边加入金属化合物W的稀释液，充分反应后，过滤、洗涤、干燥，即得复合催化剂AW；
    所述稀释剂为水、醚类、脂类、酮类、芳香族类、酰胺类、砜类或卤代烃中的一种或多种；优选为N,N-二甲基甲酰胺、乙腈或乙酸丁酯或甲基异丁基酮；进一步优选为乙腈。
  5. 根据权利要求1所述的复合催化剂，其特征在于，由包括以下步骤的方法制备而成：配制氯化亚铜、氯化铜或氯化锰的乙腈稀释液，常温常压下边搅拌边加入1,4-二氮杂二环[2.2.2]辛烷或2-甲基-1,4-二氮杂二环[2.2.2]辛烷的乙腈稀释液，加入至二者的摩尔比为1:1后，继续反应完全，过滤，用乙腈洗涤，干燥，即得。
  6. 复合催化剂AW在催化合成不对称4,6-双芳氧基嘧啶衍生物中的应用，其特征在于，所述复合催化剂由化合物A或/和其盐与金属化合物W复合而成；所述化合物A具有通式I所示结构：
    Figure PCTCN2016104375-appb-100002
    所述通式I中，R1、R3、R5、R6各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基、芳基或酯基；R2、R4各自独立地代表氢、卤素、C1～C10的含氧或不含氧脂肪烃基或芳基；
    所述金属化合物W为金属卤化物、酸式金属、碱式金属、烷基金属或芳基金属及其水合物中的一种或多种，其中，所述金属为铜、锰、钴、镍、钯、铁、铝或锌；
    所述化合物A或/和其盐与金属化合物W以AmWn的形式复合而成，其中，A与W的摩尔比m:n为1～2:1或1:1～2；
    所述不对称4,6-双芳氧基嘧啶衍生物优选为如通式II所示的结构：
    Figure PCTCN2016104375-appb-100003
    所述通式II中，G1代表氢或卤素，G3代表卤素或氰基，G2代表
    Figure PCTCN2016104375-appb-100004
    所述不对称4,6-双芳氧基嘧啶衍生物更优选为嘧菌酯和氟嘧菌酯。
  7. 根据权利要求6所述的应用，其特征在于，所述不对称4,6-双芳氧基嘧啶衍生物的合成路线为：
    Figure PCTCN2016104375-appb-100005
    其中，所述G1代表氢或卤素；所述G3代表卤素或氰基；所述G2代表
    Figure PCTCN2016104375-appb-100006
    具体包括以下步骤：
    (1)以化合物1和化合物2或化合物2的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物3；该步骤中，复合催化剂AW的用量为化合物1的0.1～50mol％；
    (2)所述化合物3和化合物4或化合物4的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物5，即可；该步骤中，复合催化剂AW的用量为化合物3的0.1～50mol％。
  8. 根据权利要求6所述的应用，其特征在于，所述不对称4,6-双芳氧基嘧啶衍生物的合成路线为：
    Figure PCTCN2016104375-appb-100007
    其中，所述G1代表氢或卤素；所述G3代表卤素或氰基；所述G2代表
    Figure PCTCN2016104375-appb-100008
    具体包括以下步骤：
    (1)以化合物1和化合物4或化合物4的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物6；该步骤中，复合催化剂AW的用量为化合物1的0.1～50mol％；
    (2)所述化合物6和化合物2或化合物2的碱金属盐为原料，在复合催化剂AW存在条件下，进行醚化反应，得化合物5，即可；该步骤中，复合催化剂AW的用量为化合物6的0.1～50mol％。
  9. 根据权利要求7或8所述的应用，其特征在于，所述两步醚化反应为分步进行，或在同一反应器中先进行其中一步醚化反应，然后接着进行另一步醚化反应，或在同一反应器中同时进行两步醚化反应；
    反应溶剂为醚类、脂类、酮类、芳香族类、酰胺类、砜类或卤代烃中的一种或多种；优选为N,N-二甲基甲酰胺或乙腈或乙酸丁酯或甲基异丁基酮；进一步优选为乙腈；
    反应温度为：10～180℃；优选为30～120℃；进一步优选为60～80℃。
  10. 根据权利要求6～9任意一项所述的应用，其特征在于，所述 复合催化剂AW在催化合成不对称4,6-双芳氧基嘧啶衍生物后，采用以下方法进行回收：
    反应终止后，经脱溶、酸化和萃取，分离出水层，调节水层pH值至4～8，析出固体，过滤，干燥，得到回收的催化剂。
PCT/CN2016/104375 2016-02-05 2016-11-02 一种复合催化剂及其应用 WO2017133283A1 (zh)

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CN110280307B (zh) * 2019-04-29 2022-06-10 内蒙古灵圣作物科技有限公司 一种氮杂双环类配合物催化剂及其制备方法与应用
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1419549A (zh) * 2000-03-24 2003-05-21 拜尔公司 不对称的4,6－双(芳氧基)嘧啶衍生物的制备方法
CN101522639A (zh) * 2006-10-09 2009-09-02 先正达有限公司 嘧菌酯的制备
CN102276538A (zh) * 2011-08-12 2011-12-14 河北威远生物化工股份有限公司 嘧菌酯及其关键中间体的制备方法
CN105536873A (zh) * 2016-02-05 2016-05-04 帕潘纳(北京)科技有限公司 一种复合催化剂及其应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104311493B (zh) * 2014-09-16 2016-08-24 重庆紫光国际化工有限责任公司 嘧菌酯的合成方法
CN104230819B (zh) * 2014-09-16 2017-05-03 重庆紫光国际化工有限责任公司 嘧菌酯的合成方法
CN104974097B (zh) * 2015-05-29 2018-04-17 重庆紫光化工股份有限公司 一种嘧菌酯的合成方法

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1419549A (zh) * 2000-03-24 2003-05-21 拜尔公司 不对称的4,6－双(芳氧基)嘧啶衍生物的制备方法
CN101522639A (zh) * 2006-10-09 2009-09-02 先正达有限公司 嘧菌酯的制备
CN102276538A (zh) * 2011-08-12 2011-12-14 河北威远生物化工股份有限公司 嘧菌酯及其关键中间体的制备方法
CN105536873A (zh) * 2016-02-05 2016-05-04 帕潘纳(北京)科技有限公司 一种复合催化剂及其应用

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