CN103739574A - Synthetic method of substitutive 5H-furan-2-ketone compound - Google Patents

Synthetic method of substitutive 5H-furan-2-ketone compound Download PDF

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CN103739574A
CN103739574A CN201310754058.0A CN201310754058A CN103739574A CN 103739574 A CN103739574 A CN 103739574A CN 201310754058 A CN201310754058 A CN 201310754058A CN 103739574 A CN103739574 A CN 103739574A
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selenium
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thf
resin
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CN103739574B (en
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王宇光
何荣军
朱冰春
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Zhejiang University of Technology ZJUT
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/58—One oxygen atom, e.g. butenolide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins

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Abstract

The invention discloses a synthetic method of a substitutive 5H-furan-2-ketone compound shown by a formula (IV) or (VI). The synthetic method is specifically shown by the following equations. According to the synthetic method, the combination of an efficient catalyst and a solvent is adopted in an electrophilic cyclization reaction between selenium resin (I) and butenic acid (II) to ensure that a target compound synthetic through the cyclization reaction is good in purity and high in yield; besides, only filtering and washing are needed after the reaction of each step is ended, and tedious separation and purification are not needed, so that the entire synthesis process is simple in operation.

Description

A kind of synthetic method of 5H-furans-2-ketone compounds of replacement
Technical field
The present invention relates to the synthetic method of the 5H-furans-2-ketone compounds shown in a kind of formula (IV) or formula (VI);
Figure BDA0000450463290000011
Background technology
Combinatorial chemistry results from the eighties in 20th century, arrived twentieth century nineties, fast development due to world's pharmacy industry, thereby strengthened the pressure of new drug development and high flux screening (high-throughput screening), as how higher efficiency, carry out synthetic organic molecule and for screening, become the key of problem, under such background, combinatorial chemistry has obtained unprecedented fast development just.Up to the present, combinatorial chemistry has been broken away from its initial stage and has only been confined to the application situation of new medicament screen, and is widely used in chemicobiology, Materials science, asymmetry catalysis, even domain of inorganic chemistry.Wherein, solid phase organic synthesis (SPOS, solid phase organic synthesis) is the core technology in synthetic combination of compounds storehouse, is the basis of combinatorial chemistry.(Merrifield since Americanized scholar Merrifield in 1963 proposes solid phase synthesis, R.B.J.Am.Chem.Soc., 1963,85 (14), 2149-2154.), SPOS is applied in synthesizing of polypeptide (peptide) and nucleic acid oligomer (oligonucleotide) very soon.The work of Bunin, Ellman, Chiron and Parke-Davis research group (Bunin, B.A., et al.J.Am.Chem.Soc., 1992,114 (27), 10997-10998; Balkenhohl F,, et al.Angew.Chem.Int.Ed., 1996,35 (20), 2288-2337.) become the sign that SPOS enters high speed development, micromolecular combination becomes the leading role of SPOS.
5H-furans-2-ketone compounds is present in numerous natural product skeletons, has biological activity (Wang X.J.et al.Bioorganic & Medicinal Chemistry Letters, 2011,21,3074-3077 very widely; Brider, T., et al.Tetrahedron Letters, 2011,52,3640-3644; Eifler-Lima, V.L., et al.J.Braz.Chem.Soc., 2010.21 (8), 1401-1423; Nicolaou, K.C., et al.Handbook of Combinatorial Chemistry; Wiley-VCH:Weinheim, 2002; Testero, S.A., et al.J.Comb.Chem., 2008,10,487-497.).For example, 5H-furans-2-ketone compounds can be used as potential antiphlogiston, and microbiotic is antitumor, antiviral, transformation reactions inhibitor, cyclooxygenase-2 inhibitors, seed germination inhibitor, PLA 2 inhibitors, plant-growth regulator, sterilant.In addition, relatively simple α, β-unsaturated butyrolactone yet can be used as preparation (Madsen, P., et al.J.Med.Chem.2009,52, the 2989-3000 of the synthetic intermediate of physiologically active compound; Dolle, R.E., et al.J.Comb.Chem.2010,12,765-806; Duval, R., et al.J.Comb.Chem.2009,11,947-950; Lafleur, K., et al.J.Med.Chem.2009,52,6433-6446.).
Summary of the invention
First technical problem that the present invention will solve is to provide the synthetic method of 5H-furans-2-ketone compounds of the replacement shown in a kind of formula (IV), and the method is simple to operate, convenient post-treatment, and product yield is high, purity good.
Second technical problem that the present invention will solve is to provide the synthetic method of 5H-furans-2-ketone compounds of the replacement shown in a kind of formula (VI), and the method is simple to operate, convenient post-treatment, and product yield is high, purity good.
Below technical scheme of the present invention is illustrated.
The synthetic method that the invention provides 5H-furans-2-ketone compounds of the replacement shown in a kind of formula (IV), comprises the steps:
(1) take the selenium bromide reagent (be called for short selenium bromine resin) of the loaded by polystyrene shown in formula (I) and the butenoic acid of the replacement shown in formula (II) is raw material, using silver trifluoromethanesulfonate (AgOTf) and hempa selenium acyl triamine (HMPA (Se)) as catalyzer, the resin-carried Gamma Butyrolactone of selenium shown in the selenium electric ring closure reaction production of parent (III) occurs in organic solvent A; It is one of following that described organic solvent is selected from: tetrahydrofuran (THF) (THF), methylene dichloride, DMF(N, dinethylformamide) and the mixed solvent of THF;
(2) the resin-carried Gamma Butyrolactone of selenium obtains 5H-furans-2-ketone compounds of the replacement shown in formula (IV) after hydrogen peroxide oxidation is eliminated cutting;
Reaction formula is as follows:
Figure BDA0000450463290000021
In formula (II), formula (III) or formula (IV), R 1be selected from one of following groups: the phenyl that the alkyl of H, C1～C15, phenyl, benzyl, halogen replace; R 2be selected from one of following groups: the alkyl of H, C1～C15, phenyl, benzyl; Or R 1and R 2form the cycloalkyl of C5～C6; R 3be selected from one of following groups: H, the alkyl of C1～C15, phenyl, carboxyl.
Further, R 3be selected from one of following groups: H, the alkyl of C1～C6, phenyl, carboxyl.
In described step (1), the selenium bromine resin of loaded by polystyrene is according to document (Wang Yuguang, the preparation of loaded by polystyrene organoselenium reagent and the application in heterogeneous ring compound is synthetic thereof, 2007, Zhejiang University's Ph D dissertation) preparation, it is 1.02mmol/g that this patent is used carrying capacity on the selenium of selenium bromine resin.
Further, in described step (1), the molar ratio of the butenoic acid of the selenium bromide reagent of loaded by polystyrene (take selenium on carrying capacity calculate), silver trifluoromethanesulfonate, hempa selenium acyl triamine and replacement is 1:1:0.05-0.2:2-4, is preferably 1:1:0.1:3.
Further, in described step (1), temperature of reaction is at-5～55 ℃, and the reaction times was at 3～16 hours.
Further, described organic solvent A is preferably DMF(N, dinethylformamide) and the mixed solvent of THF.
Further, described THF and DMF(N, dinethylformamide) mixed solvent in, THF and DMF(N, dinethylformamide) volume ratio >=4, be preferably 4～10:1.
Further, after step (1) reacts completely, reaction solution after filtration, wash, be drying to obtain the resin-carried Gamma Butyrolactone of selenium.
Further, described washing is preferably carried out in the following manner: filter and to obtain tetrahydrofuran (THF) that tetrahydrofuran (THF) that filter cake is 1:1 by DMF, ethyl acetate, water, tetrahydrofuran (THF), volume ratio successively and water mixed liquid, tetrahydrofuran (THF), volume ratio are 1:1 and water mixed liquid, tetrahydrofuran (THF), washed with dichloromethane.
Again further, described step (1) is preferably according to following enforcement: under nitrogen atmosphere, the selenium bromine resin of loaded by polystyrene is fully soaked in THF, in-5 ℃～5 ℃ ℃, add silver trifluoromethanesulfonate stirring reaction 10～20min, add again hempa selenium acyl triamine and DMF, be warming up to the butenoic acid of the replacement shown in the formula (II) of THF and DMF dissolving for 20～30 ℃ of droppings, stirring reaction is warming up to 45～55 ℃ of stirring reactions 3～12 hours after 1.5～2.5 hours, reaction finishes rear filtration, filter cake washing, be dried and obtain the resin-carried Gamma Butyrolactone of selenium shown in formula (III).
Further, in described step (2), the Gamma Butyrolactone that selenium is resin-carried and H 2o 2molar ratio be 1:9～11.
Further, the described reaction of step (2) is usingd organic solvent B as reaction solvent, and organic solvent B is THF preferably.
Further, in described step (2), temperature of reaction is at 0～25 ℃, and the reaction times was at 0.5～2.0 hour.
Further, after step (2) reacts completely, reacting liquid filtering, filtrate boils off solvent, resistates dichloromethane extraction, organic layer drying, the concentrated 5H-furans-2-ketone compounds that obtains formula (IV) replacement.
The present invention also provides the synthetic method of 5H-furans-2-ketone compounds of the replacement shown in a kind of formula (VI), comprises the steps:
(a) take the selenium bromide reagent (be called for short selenium bromine resin) of the loaded by polystyrene shown in formula (I) and the butenoic acid of the replacement shown in formula (II) is raw material, using silver trifluoromethanesulfonate (AgOTf) and hempa selenium acyl triamine (HMPA (Se)) as catalyzer, the resin-carried Gamma Butyrolactone of selenium shown in the selenium electric ring closure reaction production of parent (III) occurs in organic solvent A; It is one of following that described organic solvent is selected from: tetrahydrofuran (THF) (THF), methylene dichloride, DMF(N, dinethylformamide) and the mixed solvent of THF;
(b) the resin-carried Gamma Butyrolactone of the selenium shown in formula (III) under the catalysis of lithium diisopropylamine (LDA) with halogenated compound R 4x reaction generates the resin-carried Gamma Butyrolactone of selenium shown in formula V;
(c) the resin-carried Gamma Butyrolactone of the selenium shown in formula V obtains 5H-furans-2-ketone compounds of the replacement shown in formula (VI) after hydrogen peroxide oxidation is eliminated cutting;
Reaction formula is as follows:
Figure BDA0000450463290000031
Wherein, R 1be selected from one of following groups: the phenyl that the alkyl of H, C1～C15, phenyl, benzyl, halogen replace; R 2be selected from one of following groups: the alkyl of H, C1～C15, phenyl, benzyl; Or R 1and R 2form the cycloalkyl of C5～C6; R 3be selected from one of following groups: H, the alkyl of C1～C15, phenyl, carboxyl; R 4be selected from one of following groups: the alkyl oxy carbonyl of the alkyl of C1～C10, C1～C4, X is halogen.
Further, R 3be selected from one of following groups: H, the alkyl of C1～C6, phenyl, carboxyl.
Further, R 4be selected from one of following groups: the alkyl oxy carbonyl of the alkyl of C1～C6, C1～C4.
The same above-mentioned steps of described step (a) (1), preparation details does not repeat them here.
Further, in described step (b), Gamma Butyrolactone, halogenated compound R that the selenium shown in formula (III) is resin-carried 4the molar ratio of X, butyllithium is 1:1～1.3.:1～1.3.
Further, the described reaction of step (b) is carried out in reaction solvent, and described reaction solvent is THF.
Further, in step (b), temperature of reaction is at-30～-70 ℃, and the reaction times was at 1～2 hour.
Further, after step (b) reacts completely, reaction solution after filtration, washing, the dry resin-carried Gamma Butyrolactone of the selenium shown in formula V that obtains.
Further, described washing is preferably according to carrying out as follows: the tetrahydrofuran (THF) that the tetrahydrofuran (THF) that the filter cake that filtration obtains is 1:1 by tetrahydrofuran (THF), water, tetrahydrofuran (THF), volume ratio successively and water mixed liquid, tetrahydrofuran (THF), volume ratio are 1:1 and water mixed liquid, tetrahydrofuran (THF) washing.
Further, in described step (c), the Gamma Butyrolactone that the selenium shown in formula V is resin-carried and H 2o 2molar ratio be 1:9～11.
Further, the described reaction of step (c) is usingd organic solvent B as reaction solvent, and organic solvent B is THF preferably.
Further, in described step (c), temperature of reaction is at 0～25 ℃, and the reaction times was at 0.5～2.0 hour.
Further, after step (c) reacts completely, reacting liquid filtering, filtrate boils off solvent, resistates dichloromethane extraction, organic layer drying, the concentrated 5H-furans-2-ketone compounds that obtains formula (VI) replacement.
Compared with prior art, the invention has the advantages that:
In parent's electricity ring closure reaction of selenium resin (I) and butenoic acid (II), adopt efficient catalyzer (combination of silver trifluoromethanesulfonate and hempa selenium acyl triamine) and solvent combination, make ring closure reaction effect very outstanding, synthetic target compound purity is good, yield is high; In addition, after every step reaction finishes, only need filtration washing, do not need loaded down with trivial details separating-purifying, whole synthesis program is simple to operate, makes the method be more suitable for, in building such compound library, being applied in the middle of the development research of new drug.
Embodiment
Below in conjunction with specific embodiment, the present invention is described further, but protection scope of the present invention is not limited in this:
The preparation of embodiment 1:5-phenyl-5H-furans-2-ketone (IV-1)
Reaction formula is as follows:
Figure BDA0000450463290000051
(1) under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.590 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1, with 12mL THF/DMF=5:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 3.0 hours.Reaction finishes rear filtration, filter cake is used 20mL DMF, 20mL ethyl acetate, 40mL water, 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), 20mL tetrahydrofuran (THF), 20mL washed with dichloromethane successively, dry, make the selenium resin shown in formula (III-1).
(2) dry constant weight method is measured the yield of the selenium electric ring closure reaction product resin of parent (III-1).
The resin (III-1) wash in step (1) vacuum-drying under 45 ℃, 100Pa is arrived to constant weight, be weighed as 0.6370g, formula obtains the yield Y of resin (III-1) below substitution iII-1for 96.3%.
Y III - 1 = ( G III - 1 - G I ) × 1000 ( M II - 1 - M H - M Br ) × ∩ Se = ( G III - 1 - 0.590 ) × 1000 ( M II - 1 - 80.9 ) × 0.60 = ( 0.6370 - 0.590 ) × 1000 ( 162.2 - 80.9 ) × 0.60 = 0.963
Wherein, G iII-1for resin (III-1) weight, G ifor resin (I) charging capacity, M iI-1for II-1 molecular weight, M hfor hydrogen atom nucleidic mass, M brfor bromine atoms nucleidic mass, ∩ seupper carrying capacity (mmol) for resin (I) selenium.
(3) the selenium resin shown in formula (III-1) is soaked 5.0 hours in 20mL THF, adds again 0.61mL(6mmol at 0 ℃) 30% H 2o 2the aqueous solution, 0 ℃ is reacted 0.5 hour, 25 ℃ are reacted 1.0 hours again, reaction finishes, reacting liquid filtering, filter cake is used 20mL tetrahydrofuran (THF) successively, 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF), merging filtrate, boil off THF, resistates dichloromethane extraction, organic layer drying, concentrate and make the compound 0.0878g shown in formula (IV-1), yield 91.3%, its purity of high-performance liquid chromatogram determination is 97%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 96.3%, the structural characterization of compound (IV-1) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.55-7.51(m,2H),7.44-7.34(m,3H),
7.29-7.27(m,1H),6.25(m,1H),6.01(s,1H);MS(EI):m/z160(M +).
The preparation of embodiment 2:5-phenyl-5H-furans-2-ketone (IV-1)
(1) under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.590 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 5mL DMF, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1, with 10mL THF/DMF=4:1, dissolve), below operation, with embodiment 1, finally makes the compound 0.0876g shown in formula (IV-1), yield 91.1%, its purity of high-performance liquid chromatogram determination is 97%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 96.2%
The preparation of embodiment 3:5-phenyl-5H-furans-2-ketone (IV-1)
(1) under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.590 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 2mL DMF, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1, with 11mL THF/DMF=10:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 6.0 hours.Below operate same embodiment 1, finally make the compound 0.0874g shown in formula (IV-1), yield 90.9%, its purity of high-performance liquid chromatogram determination is 97%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 96.0%,
The preparation of embodiment 4:5-phenyl-5H-furans-2-ketone (IV-1)
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1, with 12mL THF, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 12 hours.Below operate same embodiment 1, finally make the compound 0.0870g shown in formula (IV-1), yield 90.5%, its purity of high-performance liquid chromatogram determination is 96%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 95.4%.
The preparation of embodiment 5:5-phenyl-5H-furans-2-ketone (IV-1)
Under nitrogen atmosphere, by the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g at 20mL CH 2cl 2middle immersion 10 hours, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (12mL CH is used in II-1 2cl 2dissolve), drip stirring reaction after 2.0 hours, back flow reaction 12 hours.Below operate same embodiment 1, finally make the compound 0.0851g shown in formula (IV-1), yield 88.6%, its purity of high-performance liquid chromatogram determination is 94%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 93.3%.
The preparation of embodiment 6:5-phenyl-5H-furans-2-ketone (IV-1)
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.145g (0.06mmol) hempa selenium acyl triamine, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1, with 12mL THF, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 12 hours.Below operate same embodiment 1, finally make the compound 0.0830g shown in formula (IV-1), yield 86.4%, purity is 90%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 90.9%.
The preparation of embodiment 7:5-phenyl-5H-furans-2-ketone (IV-1)
Under nitrogen atmosphere, by the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g at 20mL CH 2cl 2middle immersion 10 hours, 0 ℃ adds 0.145g (0.06mmol) hempa selenium acyl triamine, is warmed up to 25 ℃, in reaction, drips 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (12mL CH is used in II-1 2cl 2dissolve), drip stirring reaction after 2.0 hours, back flow reaction 12 hours.Below operate same embodiment 1, finally make the compound 0.0799g shown in formula (IV-1), yield 83.1%, purity is 87%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 88.4%.
The preparation of embodiment 8:5-phenyl-5H-furans-2-ketone (IV-1)
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.06g (0.6mmol) triethylamine, be warmed up to 25 ℃, in reaction, drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1, with 12mL THF, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 12 hours.Below operate same embodiment 1, finally make the compound 0.0338g shown in formula (IV-1), yield 35.2%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 37.6%.
The preparation of embodiment 9:5-phenyl-5H-furans-2-ketone (IV-1)
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 25 ℃ drip 0.292g (1.8mmol) 4-phenyl-3-butenoic acid (II-1 in reaction, with 12mL THF, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 12 hours.Below operate same embodiment 1, finally make the compound 0.0108g shown in formula (IV-1), yield 11.2%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 12.1%.
The preparation of embodiment 10:5-methyl-5H-furans-2-ketone (IV-2)
Reaction formula is as follows:
Figure BDA0000450463290000081
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF,-5 ℃ add 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.180g (1.8mmol) 3-pentenoic acid (II-2, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0537g shown in formula (IV-2), yield 91.2%, its purity of high-performance liquid chromatogram determination is 97%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-2) is 96.1%, and the structural characterization of compound (IV-2) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.46(d,1H),6.11(d,1H),5.15(m,1H),1.46(d,3H).MS(EI):m/z98(M +).
The preparation of embodiment 11:5-n-propyl-5H-furans-2-ketone (IV-3)
Reaction formula is as follows:
Figure BDA0000450463290000082
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.307g (2.4mmol) 3-heptenoic acid (II-3, with 12mL THF/DMF=5:1, dissolve), below operation, with embodiment 1, finally makes the compound 0.0694g shown in formula (IV-3), yield 91.7%, purity is 97%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-3) is 96.7%, and the structural characterization of compound (IV-3) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.43(dd,J=6.0,1.6Hz,1H),6.09(dd,J=6.0,2.0Hz,1H),5.02(m,1H),1.80-1.40(m,4H),0.98(t,J=7.2Hz,3H); 13C?NMR(100MHz,TMS,CDCl 3):172.88,156.14,121.49,83.11,35.2318.41,13.81.MS(EI):m/z126(M +).
The preparation of embodiment 12:5-n-heptyl-5H-furans-2-ketone (IV-4)
Reaction formula is as follows:
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.290g (0.12mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.331g (1.8mmol) 3-undecylenic acid (II-4, with 12mL THF/DMF=5:1, dissolve), below operation, with embodiment 1, finally makes the compound 0.0984g shown in formula (IV-4), yield 90.0%, purity is 96%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-4) is 95.0%, and the structural characterization of compound (IV-4) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.45(d,J=5.6,1H),6.09(d,J=5.6Hz,1H),5.03(m,1H),1.81-1.60(m,2H),1.52-1.19(m,10H),0.88(t,3H);MS(EI):m/z182(M +).
The preparation of embodiment 13:5-tertiary butyl-5H-furans-2-ketone (IV-5)
Reaction formula is as follows:
Figure BDA0000450463290000092
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.256g (1.8mmol) 5,5-dimethyl-3-hexenoic acid (II-5, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0755g shown in formula (IV-5), yield 89.8%, purity is 95%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 94.5%, and the structural characterization of compound (IV-5) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.45(dd,J=5.6,1.6Hz,1H),6.16(dd,J=5.6,2.0Hz,1H),4.76(m,1H),1.1(s,9H);MS(EI):m/z140(M +).
The preparation of embodiment 14:5-n-octyl-5H-furans-2-ketone (IV-6)
Reaction formula is as follows:
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.356g (1.8mmol) 3-lauroleic acid (II-6, with 12mL THF/DMF=5:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 5.0 hours.Below operate same embodiment 1, finally make the compound 0.1060g shown in formula (IV-6), yield 90.0%, purity is 96%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-6) is 95.1%, and the structural characterization of compound (IV-6) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.43(dd,J=5.6,1.6Hz,1H),6.16(dd,J=5.6,2.0Hz,1H),5.12(m,1H),1.84-1.61(m,2H),1.49-1.26(m,12H),0.89(t,J=6.4Hz,3H);MS(EI):m/z196(M +).
The preparation of embodiment 15:5-benzyl-5H-furans-2-ketone (IV-7)
Reaction formula is as follows:
Figure BDA0000450463290000101
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 20 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.264g (1.5mmol) 5-phenyl-3-pentenoic acid (II-7, with 12mL THF/DMF=5:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 6.0 hours.Below operate same embodiment 1, finally make the compound 0.0955g shown in formula (IV-7), yield 91.4%, purity is 97%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-7) is 96.2%, and the structural characterization of compound (IV-7) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.32(dd,J=5.6,1.6Hz,1H),7.26-7.15(m,5H),6.02(dd,J=5.6,2.0Hz,1H),5.18(m,1H),3.10(dd,J=6.4,13.6Hz,1H),2.92(dd,J=7.0,13.6Hz,1H); 13C?NMR(100MHz,TMS,CDCl 3)δ172.75,155.54,134.77,129.36,128.66,127.25,122.01,83.41,39.61.MS(EI):m/z174(M +).
The preparation of embodiment 16:5-methyl-5-phenyl-5H-furans-2-ketone (IV-8)
Reaction formula is as follows:
Figure BDA0000450463290000111
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.218g (0.09mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.317g (1.8mmol) 4-phenyl-3-pentenoic acid (II-8, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0948g shown in formula (IV-8), yield 90.7%, purity is 96%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-8) is 95.5%, and the structural characterization of compound (IV-8) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.62(d?J=5.6,1H),7.37-7.29(m,5H),6.03(d,J=5.6,1H),1.82(s,3H);MS(EI):m/z174(M +).
Embodiment 17:4, the preparation of 5-phenylbenzene-5-methyl-5H-furans-2-ketone (IV-9)
Reaction formula is as follows:
Figure BDA0000450463290000112
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.454g (1.8mmol) 3,4-phenylbenzene-3-pentenoic acid (II-9, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.1251g shown in formula (IV-9), yield 83.3%, purity is 94%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-9) is 93.4%, and the structural characterization of compound (IV-9) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.46-7.20(m,10H),6.46(s,1H),2.05(s,3H); 13C?NMR(100MHz,TMS,CDCl 3)δ171.04,170.02,136.84,129.96,128.85,128.11,128.03,127.90,127.04,125.16,113.66,87.85,22.52.MS(EI):m/z250(M +).
The preparation of embodiment 18:5-(the bromo-phenyl of 4-)-5H-furans-2-ketone (IV-10)
Reaction formula is as follows:
Figure BDA0000450463290000121
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 5mL DMF, be warmed up to 25 ℃, in reaction, drip 0.579g (2.4mmol) 4-(the bromo-phenyl of 4-)-3-butenoic acid (II-10, with 10mL THF/DMF=4:1, dissolve), below operate same embodiment 1, finally make the compound 0.1303g shown in formula (IV-10), yield 90.8%, purity is 97%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-10) is 95.9%, and the structural characterization of compound (IV-10) is as follows:
1h NMR (400MHz, TMS, CDCl 3) δ 7.56 (d, J=8.0,2H), 7.51 (d, J=5.6,1.8Hz, 1H), 7.17 (d, J=8.0,2H), 6.25 (d, J=5.6,2.0Hz, 1H), 5.97 (m, 1H); 13c NMR (100MHz, TMS, CDCl 3) δ 172.81,155.44,133.32,131.88,128.77,124.06,121.26,84.11.MS (EI): m/z238 (M +), 240 (M+2) +. embodiment 19:4, the preparation of 5-dimethyl-5H-furans-2-ketone (IV-11)
Reaction formula is as follows:
Figure BDA0000450463290000122
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.205g (1.8mmol) 3-methyl-3-pentenoic acid (II-11, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0598g shown in formula (IV-11), yield 88.9%, purity is 96%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-11) is 95.6%, and the structural characterization of compound (IV-11) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ5.71(s,1H),4.85(m,1H),2.00(s,3H),1.36(d,3H); 13CNMR(100MHz,TMS,CDCl 3)δ172.91,169.88,116.05,80.82,17.87,13.48.MS(EI):m/z112(M +).
Embodiment 20:4, the preparation of 5,5-trimethylammonium-5H-furans-2-ketone (IV-12)
Reaction formula is as follows:
Figure BDA0000450463290000131
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.231g (1.8mmol) 3,4-dimethyl-3-pentenoic acid (II-12, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0683g shown in formula (IV-12), yield 90.4%, purity is 96%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-12) is 96.2%, and the structural characterization of compound (IV-12) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ5.70(q,J=1.6Hz,1H),2.04(d,J=1.6Hz,3H),1.49(s,6H); 13C?NMR(100MHz,TMS,CDCl 3)δ173.02,171.78,115.31,87.06,24.35,12.63.MS(EI):m/z126(M +).
Embodiment 21:4, the preparation of 5-dimethyl-5-decyl-5H-furans-2-ketone (IV-13)
Reaction formula is as follows:
Figure BDA0000450463290000132
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.545g (1.8mmol) 3,4-dimethyl-3-tetradecenoic acid (II-13, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.1298g shown in formula (IV-13), yield 85.7%, purity is 95%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-13) is 94.1%, and the structural characterization of compound (IV-13) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ5.70(q,J=1.6Hz,1H),1.98(d,J=1.6Hz,3H),1.82(m,1H),1.56(m,1H),1.39(s,3H),1.31-1.01(m,16H),0.85(t,J=7.2Hz,3H); 13C?NMR(100MHz,TMS,CDCl 3)δ172.44,171.98,116.49,89.51,36.83,31.81,29.60,29.51,29.40,29.32,29.21,23.71,22.74,14.11,13.13.MS(EI):m/z252(M +).
Embodiment 22:4, the preparation of 5-dimethyl-5-benzyl-5H-furans-2-ketone (IV-14)
Reaction formula is as follows:
Figure BDA0000450463290000141
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.368g (1.8mmol) 3-methyl-4-benzyl-3-pentenoic acid (II-14, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.1069g shown in formula (IV-14), yield 88.1%, purity is 95%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-14) is 94.7%, and the structural characterization of compound (IV-14) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.27-7.15(m,5H),5.75(s,1H),3.08(m,1H),2.89(m,1H);2.02(s,3H),1.43(s,3H).MS(EI):m/z202(M +).
The preparation of embodiment 23:4-methyl isophthalic acid-oxo-spiral shell [4.5]-3-decen-2-one (IV-15)
Reaction formula is as follows:
Figure BDA0000450463290000142
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.303g (1.8mmol) 3-cyclohexylidene-butyric acid (II-15, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0918g shown in formula (IV-15), yield 92.1%, purity is 97%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-15) is 96.9%, and the structural characterization of compound (IV-15) is as follows:
1H?NMR(400MHz,TMS,CDCl 3.)　δ5.73(m,1H),2.02(d,3H),1.11-1.96(m,10H);MS(EI):m/z166(M +).
Embodiment 24:4, the preparation of 5-dimethyl-5-ethyl-5H-furans-2-ketone (IV-16)
Reaction formula is as follows:
Figure BDA0000450463290000143
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.256g (1.8mmol) 3,4-dimethyl-3-hexenoic acid (II-16, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 1, finally make the compound 0.0759g shown in formula (IV-16), yield 90.2%, purity is 96%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-16) is 96.2%, and the structural characterization of compound (IV-16) is as follows:
1H?NMR(400MHz,TMS,CDCl 3.)　δ5.60(q,J=1.8Hz,1H),2.09(d,J=1.8Hz,3H),1.76(q,J=7.2Hz,2H),1.43(s,3H),0.78(t,J=7.2Hz,3H).MS(EI):m/z140(M +).
Embodiment 25:3, the preparation of 4,5-trimethylammonium-5H-furans-2-ketone (VI--11)
Reaction formula is as follows:
Figure BDA0000450463290000151
Under nitrogen atmosphere, the selenium resin (III-11) 0.61 gram (about 0.6mmol of charge capacity of selenium) embodiment 19 being obtained with 20mLTHF soaks 6 hours in reaction flask, cool the temperature to again-70 ℃, the lithium diisopropylamine tetrahydrofuran solution 0.36mL (0.72mmol) that adds 2mol/L, stirring reaction 30 minutes; Drip wherein again 0.103g (0.72mmol) methyl iodide, continue reaction 45 minutes at-70 ℃, be warmed up to-30 ℃ and react again 15 minutes, add the 5mL shrend reaction of going out.Reaction solution proceeds to funnel and filters, filter cake is used 20mL tetrahydrofuran (THF), 40mL water, 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF) successively, dry, make the selenium resin shown in formula (V-11).
Selenium resin transfer shown in formula (V-11), to reaction flask, is soaked 5.0 hours with 20mL THF, adds again 0.61mL(6mmol at 0 ℃) 30% H 2o 2the aqueous solution, 0 ℃ is reacted 0.5 hour, and 25 ℃ are reacted 1.0 hours again, reaction finishes, reacting liquid filtering, filter cake is used 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF), merging filtrate successively, boil off THF, resistates dichloromethane extraction, organic layer drying, the concentrated compound 0.0633g shown in formula (VI-11), the yield 83.6% of making, purity is 93%, and its structural characterization is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ4.82(m,1H).1.97(s,3H),1.82(s,3H),1.41(s,3H); 13CNMR(100MHz,TMS,CDCl 3):174.41,160.53,122.55,79.40,18.05,11.62,8.22.MS(EI):m/z126(M +).
Embodiment 26:3-benzyl, the preparation of 5-n-propyl-5H-furans-2-ketone (VI-3)
Reaction formula is as follows:
Figure BDA0000450463290000161
Under nitrogen atmosphere, the selenium resin (III-3) 0.618 gram (about 0.6mmol of charge capacity of selenium) embodiment 11 being obtained with 20mLTHF soaks 6 hours in reaction flask, cool the temperature to again-70 ℃, the lithium diisopropylamine tetrahydrofuran solution 0.36mL (0.72mmol) that adds 2mol/L, stirring reaction 30 minutes; Drip wherein again 0.089g (0.72mmol) n-propyl bromide, continue reaction 45 minutes at-70 ℃, be warmed up to-30 ℃ and react again 15 minutes, add the 5mL shrend reaction of going out.Reaction solution proceeds to funnel and filters, filter cake is used 20mL tetrahydrofuran (THF), 40mL water, 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF) successively, dry, make the selenium resin shown in formula (V-3).
Selenium resin transfer shown in formula (V-3), to reaction flask, is soaked 5.0 hours with 20mL THF, adds again 0.61mL(6mmol at 0 ℃) 30% H 2o 2the aqueous solution, 0 ℃ is reacted 0.5 hour, and 25 ℃ are reacted 1.0 hours again, reaction finishes, reacting liquid filtering, filter cake is used 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF), merging filtrate successively, boil off THF, resistates dichloromethane extraction, organic layer drying, the concentrated compound 0.1121g shown in formula (VI-3), the yield 86.4% of making, purity is 95%, and its structural characterization is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.38-7.20(m,5H.),6.83-6.80(m,1H),4.96-4.87(m,1H),4.00(s,2H),1.73-1.54(m,2H),1.52-1.38(m,2H),0.95(t,3H).MS(EI):m/z216(M +).
The preparation of embodiment 27:3-methyl-4-carboxyl-5-n-pentyl-5H-furans-2-ketone (VI-17)
Reaction formula is as follows:
Figure BDA0000450463290000162
(1) under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.36g (1.8mmol) 3-carboxyl-3-nonenoic acid (II-17, with 12mL THF/DMF=5:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 3.0 hours.Below operate same embodiment 1, finally make the resin shown in formula (III-17).
(2) under nitrogen atmosphere, with 20mLTHF, 0.657 gram of selenium resin (III-17) (the about 0.6mmol of charge capacity of selenium) is soaked 6 hours in reaction flask, cool the temperature to again-70 ℃, the lithium diisopropylamine tetrahydrofuran solution 0.66mL (1.32mmol) that adds 2mol/L, stirring reaction 30 minutes; Drip wherein again 0.103g (0.72mmol) methyl iodide, continue reaction 45 minutes at-70 ℃, be warmed up to-30 ℃ and react again 15 minutes, add the 5mL shrend reaction of going out.Reaction solution proceeds to funnel and filters, filter cake is used 20mL tetrahydrofuran (THF), 40mL water, 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF) successively, dry, make the selenium resin shown in formula (V-17).
(3) by the selenium resin transfer shown in formula (V-17) to reaction flask, with 20mL THF, soak 5.0 hours, add again 0.61mL(6mmol at 0 ℃) 30% H 2o 2the aqueous solution, 0 ℃ is reacted 0.5 hour, 25 ℃ are reacted 1.0 hours again, reaction finishes, reacting liquid filtering, filter cake is used 20mL tetrahydrofuran (THF), 20mL tetrahydrofuran (THF) and water mixed liquid (volume ratio is 1:1), the washing of 20mL tetrahydrofuran (THF) successively, merging filtrate, boil off THF, resistates dichloromethane extraction, organic layer drying, concentrated makes the compound 0.1012g shown in formula (VI-17), yield 79.4%, purity is 90%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-17) is 94.9%, and the structural characterization of compound (VI-17) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ5.01(m,1H),2.18(d,3H),2.00-1.96(m,2H),1.54-1.25(m,6H),0.89(t,3H);MS(EI):m/z212(M +).
The preparation of embodiment 28:3-methyl acetate base-5-n-octyl-5H-furans-2-ketone (VI-6)
Reaction formula is as follows:
(1) under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.356g (1.8mmol) 3-lauroleic acid (II-6, with 12mL THF/DMF=5:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 3.0 hours.Below operate same embodiment 1, finally make the resin shown in formula (III-6).
(2) under nitrogen atmosphere, with 20mLTHF by selenium resin (III-6, the about 0.6mmol of charge capacity of selenium) in reaction flask, soak 6 hours, cool the temperature to again-70 ℃, the lithium diisopropylamine tetrahydrofuran solution 0.36mL (0.72mmol) that adds 2mol/L, stirring reaction 30 minutes, drip wherein again 0.110g (0.72mmol) methyl bromoacetate, below operate same embodiment 25, finally make the compound 0.1320g shown in formula (VI-6), yield 82.0%, purity is 92%, its structural characterization is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.43(q,J=2.0Hz,1H),5.17-4.96(m,1H),3.74(s,3H),3.37(t,J=2.0Hz,2H),1.86-1.27(m,14H),0.89(t,J=6.0Hz,3H); 13C?NMR(100MHz,TMS,CDCl 3)δ172.99,169.88,151.70,126.72,81.87,52.31,33.33,31.80,30.21,29.30,29.24,29.09,24.88,22.62,14.10.MS(EI):m/z268(M +).
The preparation of embodiment 29:3-methyl-4-carboxyl-5-n-tridecane base-5H-furans-2-ketone (VI-19)
Reaction formula is as follows:
Figure BDA0000450463290000181
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.562g (1.8mmol) 3-carboxyl-3-heptadecenoic acid (II-19, with 12mL THF/DMF=5:1, dissolve), below operate (1), (2), (3) in same embodiment 27, finally make the compound 0.1484g shown in formula (VI-19), yield 76.2%, purity is 89%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-19) is 92.6%, and the structural characterization of compound (VI-19) is as follows:
1h NMR (400MHz, TMS, CDCl 3) δ 5.15 (m, 1H), 2.27 (d, J=2.1Hz, 3H), 2.14-1.61 (m, 2H), 1.50-1.23 (m, 22H), 0.91 (t, 3H); 13c NMR (100MHz, TMS, CDCl 3) δ 172.77,166.34,146.82,139.80,81.45,32.69,31.91,29.66,29.61 (two carbon are overlapping), 29.58,29.51,29.37,29.33,29.23,24.82,22.68,14.11,11.02.MS (EI): m/z324 (M +).
The preparation of embodiment 30:3-methyl-4-carboxyl-5-n-octyl-5H-furans-2-ketone (VI-20)
Reaction formula is as follows:
Figure BDA0000450463290000191
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.436g (1.8mmol) 3-carboxyl-3-lauroleic acid (II-20, with 12mL THF/DMF=5:1, dissolve), below operate (1), (2), (3) in same embodiment 27, finally make the compound 0.1187g shown in formula (VI-20), yield 77.8%, purity is 90%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-20) is 94.0%, and the structural characterization of compound (VI-20) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ5.15-5.13(m,1H),2.24(d,J=2.0Hz,3H),2.09-1.22(m,14H),0.88(t,3H).MS(EI):m/z254(M +).
Embodiment 31:3, the preparation of 3-dimethyl-5-normal-butyl-5H-furans-2-ketone (VI-21)
Reaction formula is as follows:
Figure BDA0000450463290000192
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.281g (1.8mmol) 3-methyl-3-octylenic acid (II-21, with 12mL THF/DMF=5:1, dissolve), below operate same embodiment 25, finally make the compound 0.0838g shown in formula (VI-21), yield 83.0%, purity is 93%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-21) is 95.4%, and the structural characterization of compound (VI-21) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ4.67(d,J=7.6Hz,1H).1.90(s,3H),1.88-1.81(m,1H),1.76(s,3H),1.46-1.20(m,5H),0.87(t,3H); 13C?NMR(100MHz,TMS,CDCl 3):174.50,159.16,123.19,83.06,31.63,26.38,22.26,13.68,11.78,8.22.MS(EI):m/z168(M +).
The preparation of embodiment 32:3-methyl-4-carboxyl-5-phenyl-5H-furans-2-ketone (VI-22)
Reaction formula is as follows:
Figure BDA0000450463290000201
Under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF, 0 ℃ adds 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 15 minutes; Add wherein again 0.145g (0.06mmol) hempa selenium acyl triamine, 4mL DMF, be warmed up to 25 ℃, in reaction, drip 0.371g (1.8mmol) 3-carboxyl-4-phenyl-3-butenoic acid (II-22, with 12mL THF/DMF=5:1, dissolve), below operate (1), (2), (3) in same embodiment 27, finally make the compound 0.1042g shown in formula (VI-22), yield 79.6%, purity is 91%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-22) is 95.1%, and the structural characterization of compound (VI-22) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.60-7.38(m,5H),6.05(m,1H),2.17(d,3H).MS(EI):m/z218(M +).
Embodiment 33:3, the preparation of 4,5,5-tetramethyl--5H-furans-2-ketone (VI-12)
Reaction formula is as follows:
Figure BDA0000450463290000202
Under nitrogen atmosphere, the selenium resin (III-12) 0.618 gram (about 0.6mmol of charge capacity of selenium) embodiment 18 being obtained with 20mLTHF soaks 6 hours in reaction flask, next operate same embodiment 25, finally make the compound 0.0707g shown in formula (VI-12), yield 84.0%, purity is 94%, and the structural characterization of the compound shown in formula (VI-12) is as follows:
1h NMR (400MHz, TMS, CDCl 3) δ 1.94 (s, 3H), 1.79 (s, 3H), 1.41 (s, 6H); 13c NMR (100MHz, TMS, CDCl 3): 173.49,163.71,121.78,85.69,24.50,10.91,8.42.MS (EI): m/z140 (M +). embodiment 34:3-ethyl formate-4, the preparation of 5,5-trimethylammonium-5H-furans-2-ketone (VI-12-1)
Reaction formula is as follows:
Figure BDA0000450463290000211
Under nitrogen atmosphere, the selenium resin (III-12) 0.618 gram (about 0.6mmol of charge capacity of selenium) embodiment 20 being obtained with 20mLTHF soaks 6 hours in reaction flask, cool the temperature to again-70 ℃, the lithium diisopropylamine tetrahydrofuran solution 0.36mL (0.72mmol) that adds 2mol/L, stirring reaction 30 minutes; Drip wherein again 0.078g (0.72mmol) Vinyl chloroformate, next operate same embodiment 25, finally make the compound 0.1001g shown in formula (VI-12-1), yield 84.2%, purity is 94%, and the structural characterization of the compound shown in (VI-12-1) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ4.35-4.30(q,J=7.2Hz,2H),2.34(s,3H),1.49(s,6H),1.39-1.35(t,J=7.2Hz,3H); 13C?NMR(100MHz,TMS,CDCl 3):180.37,167.43,161.80,118.41,85.44,61.43,24.41,14.22,13.23.MS(EI):m/z198(M +).
Embodiment 35:3-ethyl formate-4, the preparation of 5-dimethyl-5-benzyl-5H-furans-2-ketone (IV-14)
Reaction formula is as follows:
Figure BDA0000450463290000212
Under nitrogen atmosphere, the selenium resin (III-14) 0.659 gram (about 0.6mmol of charge capacity of selenium) embodiment 22 being obtained with 20mLTHF soaks 6 hours in reaction flask, next operate same embodiment 34, finally make the compound 0.1378g shown in formula (VI-14), yield 83.7%, purity is 94%, and the structural characterization of the compound shown in formula (VI-14) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ7.26-7.15(m,5H),δ4.35-4.30(q,J=7.2Hz,2H),3.10(m,1H),2.90(m,1H);2.33(s,3H),1.46(s,3H).1.39-1.35(t,J=7.2Hz,3H).MS(EI):m/z274(M +).
The preparation of embodiment 36:3-ethyl formate-4-methyl isophthalic acid-oxo-spiral shell [4.5]-3-decen-2-one (IV-15)
Reaction formula is as follows:
Figure BDA0000450463290000213
Under nitrogen atmosphere, the selenium resin (III-15) 0.641 gram (about 0.6mmol of charge capacity of selenium) embodiment 23 being obtained with 20mLTHF soaks 6 hours in reaction flask, next operate same embodiment 34, finally make the compound 0.1227g shown in formula (VI-15), yield 85.8%, purity is 95%, and the structural characterization of the compound shown in formula (VI-15) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ4.36-4.31(q,J=7.2Hz,2H),2.31(s,3H),1.84-1.64(m,8H),1.54-1.50(m,2H),1.39-1.35(t,J=7.2Hz,3H); 13C?NMR(100MHz,TMS,CDCl 3)δ180.34,167.62,161.79,118.40,87.12,61.92,32.89,24.43,21.51,14.10,13.41.MS(EI):m/z238(M +).
White?solid,mp67-68℃?EIMS?m/z?Mp238(40),193(36),192(39),181(49),137(100).HRMS(ES-QTOF)Calcd?for?C13H19O4MpH239.1283.Found239.1280.IR?nmax(neat/cm 1):1756,1708,1636.
Embodiment 37:3-ethyl formate-4, the preparation of 5-dimethyl-5-ethyl-5H-furans-2-ketone (IV-16)
Reaction formula is as follows:
Figure BDA0000450463290000221
Under nitrogen atmosphere, the selenium resin (III-16) 0.625 gram (about 0.6mmol of charge capacity of selenium) embodiment 24 being obtained with 20mLTHF soaks 6 hours in reaction flask, next operate same embodiment 34, finally make the compound 0.1082g shown in formula (VI-16), yield 85.0%, purity is 94%, and wherein the yield of the selenium electric ring closure reaction product resin of parent (III-1) is 96.3%, and the structural characterization of compound (VI-16) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ4.37(q,J=7.2Hz,2H),2.31(s,3H),1.97(m,1H),1.76(m,1H),1.48(s,3H),1.39(m,3H),0.82(t,J=7.2Hz,3H). 13C?NMR(100MHz,TMS,CDCl 3)δ179.33,167.50,161.44,119.09,87.68,61.11,23.04,22.87,14.04,13.59,7.14.MS(EI):m/z212(M +).
The preparation of embodiment 38:3-n-hexyl-4-normal-butyl-5-methyl-5H-furans-2-ketone (IV-23)
Reaction formula is as follows:
(1) under nitrogen atmosphere, the selenium bromine resin (I) of the loaded by polystyrene of 0.59 gram of (the charge capacity 0.6mmol of selenium) 1.02mmol/g is soaked 10 hours in 20mLTHF,-2 ℃ add 0.154g (0.6mmol) silver trifluoromethanesulfonate, and stirring reaction 20 minutes; Add wherein again 0.218g (0.09mmol) hempa selenium acyl triamine, 5mL DMF, be warmed up to 25 ℃, in reaction, drip 0.375g (2.4mmol) 3-normal-butyl 3-pentenoic acid (II-23, with 10mL THF/DMF=4:1, dissolve), drip stirring reaction after 2.0 hours, be warmed up to 50 ℃ of stirring reactions 8.0 hours.Below operate same embodiment 1, finally make the resin shown in formula (III-23).
(2) under nitrogen atmosphere, with 20mLTHF by selenium resin (III-23, the about 0.6mmol of charge capacity of selenium) in reaction flask, soak 6 hours, cool the temperature to again-70 ℃, the lithium diisopropylamine tetrahydrofuran solution 0.375mL (0.75mmol) that adds 2mol/L, stirring reaction 30 minutes, drip wherein again 0.124g (0.75mmol) bromo normal hexane, below operate same embodiment 25, finally make the compound 0.1123g shown in formula (VI-23), yield 78.5%, purity is 91%, wherein the yield of the selenium electric ring closure reaction product resin of parent (III-23) is 95.0%, the structural characterization of compound (VI-23) is as follows:
1H?NMR(400MHz,TMS,CDCl 3)δ4.85(q,J=6.7Hz,1H),2.51-2.40(m,1H),2.24-2.14(m,3H),1.53-1.22(m,15H),0.92(t,J=7.2Hz,3H),0.85(t,J=6.6Hz,3H); 13C?NMR(100MHz,TMS,CDCl 3)δ174.22,164.40,127.01,77.99,31.48，30.02，29.11，28.13，26.10，23.64，22.72，22.50，18.44，14.01，13.71.MS(EI):m/z238(M +).
The electric ring closure reaction condition optimizing of table 1 selenium parent
Figure BDA0000450463290000231
Figure BDA0000450463290000241
a.the time that refers to the selenium electric ring closure reaction of parent (I+II → III), extending reaction times yield all no longer increases; b.the yield of product IV-1 be take carrying capacity is benchmark on the bromine of selenium bromine resin I pass ring, eliminate total molar yield of two steps reactions; c.the purity of IV is used high-performance liquid chromatogram determination.
The solid phase synthesis of 5H-furans-2-ketone compounds of the replacement shown in table 2 formula (IV)
Figure BDA0000450463290000242
a.refer to selenium parent electric ring closure reaction (I+II → III) molar yield; b.the yield of product IV be take carrying capacity is benchmark on the bromine of selenium bromine resin I pass ring, eliminate total molar yield of two steps reactions; c.iV purity is used high-performance liquid chromatogram determination.
The solid phase synthesis of 5H-furans-2-ketone compounds of the replacement shown in table 3 formula (VI)
Figure BDA0000450463290000251
a.refer to selenium parent electric ring closure reaction (I+II → III) molar yield; b.the yield of product VI be take carrying capacity is benchmark on the bromine of selenium bromine resin I pass ring, lithiumation, total molar yield of four-step reaction such as replace, eliminate; c.the purity of VI is used high-performance liquid chromatogram determination.

Claims (10)

1. a synthetic method for 5H-furans-2-ketone compounds of the replacement shown in formula (IV), comprises the steps:
(1) take the selenium bromide reagent of the loaded by polystyrene shown in formula (I) and the butenoic acid of the replacement shown in formula (II) is raw material, using silver trifluoromethanesulfonate and hempa selenium acyl triamine as catalyzer, the resin-carried Gamma Butyrolactone of selenium shown in the selenium electric ring closure reaction production of parent (III) occurs in organic solvent A; It is one of following that described organic solvent is selected from: tetrahydrofuran (THF), methylene dichloride, the mixed solvent of DMF and THF;
(2) the resin-carried Gamma Butyrolactone of selenium obtains 5H-furans-2-ketone compounds of the replacement shown in formula (IV) after hydrogen peroxide oxidation is eliminated cutting;
Reaction formula is as follows:
Figure FDA0000450463280000011
In formula (II), formula (III) or formula (IV), R 1be selected from one of following groups: the phenyl that the alkyl of H, C1～C15, phenyl, benzyl, halogen replace; R 2be selected from one of following groups: the alkyl of H, C1～C15, phenyl, benzyl; Or R 1and R 2form the cycloalkyl of C5～C6; R 3be selected from one of following groups: H, the alkyl of C1～C15, phenyl, carboxyl.
2. synthetic method as claimed in claim 1, is characterized in that: in described step (1), the molar ratio of the butenoic acid of the selenium bromide reagent of loaded by polystyrene, silver trifluoromethanesulfonate, hempa selenium acyl triamine and replacement is 1:1:0.05-0.2:2-4.
3. synthetic method as claimed in claim 1, is characterized in that: in described step (1), temperature of reaction is at-5～55 ℃, and the reaction times was at 3～16 hours.
4. the synthetic method as described in one of claim 1～3, is characterized in that: described organic solvent A is the mixed solvent of DMF and THF, volume ratio >=4 of THF and DMF.
5. synthetic method as claimed in claim 4, it is characterized in that described step (1) is according to following enforcement: under nitrogen atmosphere, the selenium bromine resin of loaded by polystyrene is fully soaked in THF, in-5 ℃～5 ℃, add silver trifluoromethanesulfonate stirring reaction 10～20min, add again hempa selenium acyl triamine and DMF, be warming up to the butenoic acid of the replacement shown in the formula (II) of THF and DMF dissolving for 20～30 ℃ of droppings, stirring reaction is warming up to 45～55 ℃ of stirring reactions 3～12 hours after 1.5～2.5 hours, reaction finishes rear filtration, washing, be dried and obtain the resin-carried Gamma Butyrolactone of selenium shown in formula (III).
6. a synthetic method for 5H-furans-2-ketone compounds of the replacement shown in formula (VI), comprises the steps:
(a) take the selenium bromide reagent of the loaded by polystyrene shown in formula (I) and the butenoic acid of the replacement shown in formula (II) is raw material, using hempa selenium acyl triamine and silver trifluoromethanesulfonate as catalyzer, the resin-carried Gamma Butyrolactone of selenium shown in the selenium electric ring closure reaction production of parent (III) occurs in organic solvent A; It is one of following that described organic solvent is selected from: tetrahydrofuran (THF), methylene dichloride, the mixed solvent of DMF and THF;
(b) the resin-carried Gamma Butyrolactone of the selenium shown in formula (III) under the catalysis of lithium diisopropylamine with halogenated compound R 4x reaction generates the resin-carried Gamma Butyrolactone of selenium shown in formula V;
(c) the resin-carried Gamma Butyrolactone of the selenium shown in formula V obtains 5H-furans-2-ketone compounds of the replacement shown in formula (VI) after hydrogen peroxide oxidation is eliminated cutting;
Reaction formula is as follows:
Figure FDA0000450463280000021
Wherein, R 1be selected from one of following groups: the phenyl that the alkyl of H, C1～C15, phenyl, benzyl, halogen replace; R 2be selected from one of following groups: the alkyl of H, C1～C15, phenyl, benzyl; Or R 1and R 2form the cycloalkyl of C5～C6; R 3be selected from one of following groups: H, the alkyl of C1～C15, phenyl, carboxyl; R 4be selected from one of following groups: the alkyl oxy carbonyl of the alkyl of C1～C10, C1～C4, X is halogen.
7. synthetic method as claimed in claim 6, is characterized in that: in described step (a), the molar ratio of the butenoic acid of the selenium bromide reagent of loaded by polystyrene, silver trifluoromethanesulfonate, hempa selenium acyl triamine and replacement is 1:1:0.05-0.2:2-4.
8. synthetic method as claimed in claim 6, is characterized in that: in described step (a), temperature of reaction is at-5～55 ℃, and the reaction times was at 3～16 hours.
9. the synthetic method as described in one of claim 6～8, is characterized in that: described organic solvent A is the mixed solvent of DMF and THF, volume ratio >=4 of THF and DMF.
10. synthetic method as claimed in claim 9, it is characterized in that described step (a) is according to following enforcement: under nitrogen atmosphere, the selenium bromine resin of loaded by polystyrene is fully soaked in THF, in-5 ℃～5 ℃ ℃, add silver trifluoromethanesulfonate stirring reaction 10～20min, add again hempa selenium acyl triamine and DMF, be warming up to the butenoic acid of the replacement shown in the formula (II) of THF and DMF dissolving for 20～30 ℃ of droppings, stirring reaction is warming up to 45～55 ℃ of stirring reactions 3～12 hours after 1.5～2.5 hours, reaction finishes rear filtration, filter cake washing, be dried and obtain the resin-carried Gamma Butyrolactone of selenium shown in formula (III).
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