CN114181182A - Synthesis method of polysubstituted 4H-pyran compound - Google Patents
Synthesis method of polysubstituted 4H-pyran compound Download PDFInfo
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- CN114181182A CN114181182A CN202111565733.6A CN202111565733A CN114181182A CN 114181182 A CN114181182 A CN 114181182A CN 202111565733 A CN202111565733 A CN 202111565733A CN 114181182 A CN114181182 A CN 114181182A
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- -1 polysubstituted 4H-pyran compound Chemical class 0.000 title claims abstract description 12
- 238000001308 synthesis method Methods 0.000 title abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 12
- 238000004440 column chromatography Methods 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 9
- 150000000531 4H-pyrans Chemical class 0.000 claims abstract description 7
- 239000002841 Lewis acid Substances 0.000 claims abstract description 7
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 7
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 5
- 238000003756 stirring Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000012046 mixed solvent Substances 0.000 claims description 8
- 239000003208 petroleum Substances 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- PDPJQWYGJJBYLF-UHFFFAOYSA-J hafnium tetrachloride Chemical compound Cl[Hf](Cl)(Cl)Cl PDPJQWYGJJBYLF-UHFFFAOYSA-J 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- UCYRAEIHXSVXPV-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)indiganyl trifluoromethanesulfonate Chemical compound [In+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F UCYRAEIHXSVXPV-UHFFFAOYSA-K 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 238000001311 chemical methods and process Methods 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- JKNHZOAONLKYQL-UHFFFAOYSA-K tribromoindigane Chemical compound Br[In](Br)Br JKNHZOAONLKYQL-UHFFFAOYSA-K 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 2
- GYCHYNMREWYSKH-UHFFFAOYSA-L iron(ii) bromide Chemical compound [Fe+2].[Br-].[Br-] GYCHYNMREWYSKH-UHFFFAOYSA-L 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 239000012295 chemical reaction liquid Substances 0.000 description 5
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 3
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- 238000007115 1,4-cycloaddition reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses a method for synthesizing a polysubstituted 4H-pyran compound, belonging to the field of organic synthesis. The method comprises the following steps: under the protection of nitrogen, adding beta, gamma-unsaturated-alpha-keto ester, alkyne, Lewis acid and solvent into a reactor in turn, stirring at a certain temperature until the reaction is finished, and separating by column chromatography to obtain the polysubstituted 4H-pyran compounds. The synthesis method has the advantages of high yield, wide substrate application range, simple operation, mild reaction conditions, convenient post-treatment and the like. The reaction equation is as follows:
Description
Technical Field
The invention discloses a method for synthesizing a polysubstituted 4H-pyran compound, belonging to the technical field of organic synthesis.
Background
Polysubstituted 4H-pyran compounds are important organic heterocyclic molecules, widely exist in natural products, and have good biological activity and pharmacological activity (bioorg. Med. chem.,2004,12, 2199-2218); other types of heterocyclic compounds and functional molecules, such as Dyes (J.Org.chem.,2021,86,3213-3222), organic light emitting materials (Dyes Pigments,2021,193,109537), etc., can also be constructed as synthons. The [4+2] cycloaddition reaction of α, β -unsaturated carbonyl compounds with alkynes is one of the common methods for synthesizing such compounds. The methods reported at present all need to use preactivated alpha, beta-unsaturated carbonyl compounds, and the substrate range is limited; noble metal catalysis is needed in the reaction, and the reaction conditions are harsh (J.Am.chem.Soc.,2009,131, 1350-1071; J.Am.chem.Soc.,2015,137, 12478-12481; Org.Lett.,2018,20, 1074-1077). Therefore, the development of a novel synthesis method of the polysubstituted 4H-pyran compound with mild condition and wide substrate applicability is of great significance.
Disclosure of Invention
The invention aims to overcome the problems of limited substrate, harsh reaction conditions and the like in the existing synthesis process of the polysubstituted 4H-pyran compounds, and provides a novel synthesis method of the polysubstituted 4H-pyran compounds, which has mild conditions and wide substrate applicability.
In order to achieve the above object, the present invention provides a method for synthesizing a polysubstituted 4H-pyran compound, wherein the chiral polysubstituted 4H-pyran compound has a structure represented by formula I:
wherein R is1Is selected from any one of saturated alkyl, substituted alkyl, aryl, substituted aryl, naphthyl and thienyl.
R2Is selected from any one of methyl, ethyl and isopropyl.
R3、R4Selected from any two of saturated alkyl, substituted alkyl, aryl, substituted aryl, naphthyl and thienyl which are the same or different.
The substituent of the substituted alkyl and the substituted aryl is any one of halogen atom, saturated alkyl, aryl, ester group, trifluoromethyl, nitro, hydroxyl and alkoxy.
The method comprises the following steps: under the protection of nitrogen, sequentially adding beta, gamma-unsaturated-alpha-keto ester, alkyne, Lewis acid and a solvent into a reactor, stirring at a certain temperature until the reaction is finished, and performing column chromatography separation to obtain a polysubstituted 4H-pyran compound, wherein the chemical process is shown as a reaction formula II:
the Lewis acid is any one of ferric bromide, hafnium chloride, indium bromide and indium trifluoromethanesulfonate.
The solvent is any one of dichloromethane, trichloromethane, 1, 2-dichloroethane, tetrahydrofuran, toluene and acetonitrile.
The mol ratio of the beta, gamma-unsaturated-alpha-keto ester, the alkyne and the Lewis acid is 1.0 (1.0-10.0) to 0.05-0.3.
The reaction time is 0.5-6 h.
The reaction temperature is 0-60 ℃.
After the reaction, the mixed solvent of petroleum ether and ethyl acetate is used for column chromatography separation.
The invention has the beneficial effects that: the synthesis method of the polysubstituted 4H-pyran compound provided by the invention is scientific and reasonable, and has the advantages of high yield, wide substrate application range, simplicity in operation, mild reaction conditions, convenience in post-treatment and the like.
Drawings
FIG. 1 is an NMR spectrum of a compound (3aa) prepared in example 1;
FIG. 2 is an NMR spectrum of the compound (3ba) prepared in example 2;
FIG. 3 is an NMR spectrum of a compound (3ca) prepared in example 3;
FIG. 4 is an NMR spectrum of a compound (3db) prepared in example 4;
FIG. 5 is an NMR spectrum of compound (3dc) prepared in example 5;
FIG. 6 is an NMR spectrum of the compound (3dd) prepared in example 6.
Detailed Description
The method of the present invention is described herein by way of specific examples, but the present invention is not limited thereto, and any modifications, equivalents, improvements, etc. made within the technical spirit of the present invention should be included within the scope of the present invention.
Example 1:
the reaction equation is as follows:
under nitrogen protection, compound 1a (5mmol), 2a (20mmol) and hafnium chloride (1.0mmol) were charged into a reactor, 50mL of dichloromethane was added, and the mixture was stirred at room temperature until the reaction was completed. After the reaction is finished, a crude product obtained by concentrating the reaction solution by a rotary evaporator is separated by column chromatography by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1 to obtain pure 3aa with the yield of 75%.
Nuclear magnetic data for 3aa are as follows:
1H NMR(500MHz,CDCl3)δ7.31(d,J＝6.3Hz,6H),7.24(dd,J＝5.9,3.7Hz,1H),7.19-7.12(m,3H),7.09-7.01(m,3H),6.86(d,J＝7.3Hz,2H),6.30(d,J＝5.4Hz,1H),5.15(dt,J＝12.4,6.2Hz,1H),4.31(d,J＝5.4Hz,1H),1.31(dd,J＝5.8,4.3Hz,6H)ppm.
13C NMR(125MHz,CDCl3)δ161.37,147.16,144.16,140.75,139.03,134.37,129.73,129.35,128.88,128.49,128.27,128.08,127.75,127.21,126.85,114.14,113.41,69.10,45.02,21.85ppm.
example 2
The reaction equation is as follows:
under nitrogen protection, compound 1b (5mmol), 2a (20mmol) and hafnium chloride (1.0mmol) were charged into a reactor, 50mL of 1, 2-dichloroethane was added, and the mixture was stirred at room temperature until the reaction was completed. After the reaction is finished, a crude product obtained by concentrating the reaction liquid by a rotary evaporator is subjected to column chromatography separation by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1 to obtain pure 3ba with the yield of 82%.
Nuclear magnetic data for 3ba are as follows:
1H NMR(500MHz,DMSO-d6)δ7.49-7.48(m,1H),7.28(d,J＝2.0Hz,1H),7.253-7.23(m,5H),7.14-7.10(m,3H),7.04-7.03(m,1H),6.94-6.92(m,2H),6.29(d,J＝5.5Hz,1H),4.66(d,J＝5.5Hz,1H),4.26-4.20(m,2H),1.25(t,J＝7.0Hz,3H)ppm.
13C NMR(125MHz,DMSO-d6)δ160.84,144.16,139.78,134.05,129.21,129.02,128.44,128.04,127.86,127.46,126.86,122.34,114.29,113.35,61.09,13.98ppm.
example 3
The reaction equation is as follows:
under nitrogen protection, compound 1c (5mmol), 2a (20mmol) and indium trifluoromethanesulfonate (1.0mmol) were charged in a reactor, 50mL of dichloromethane was added, and the mixture was stirred at room temperature until the reaction ended. After the reaction is finished, a crude product obtained by concentrating the reaction liquid by a rotary evaporator is subjected to column chromatography separation by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1 to obtain pure 3ca with the yield of 37%.
Nuclear magnetic data for 3ca are as follows:
1H NMR(500MHz,CDCl3)δ7.23-7.16(m,5H),7.15-7.08(m,5H),6.22-3.18(m,1H),4.40-4.21(m,2H),3.46-3.43(m,1H),1.50-1.41(m,3H),1.37-1.33(m,4H),0.85(t,J＝6.5Hz,3H)ppm.
13C NMR(125MHz,CDCl3)δ161.85,146.81,141.96,138.91,134.57,129.47,129.07,128.37,127.88,127.58,126.77,114.38,114.14(d,J＝22.9Hz),68.89,61.26,37.81,37.04,21.83,18.65,14.18(d,J＝18.7Hz)ppm.
example 4
The reaction equation is as follows:
under nitrogen protection, compound 1d (5mmol), 2b (20mmol) and hafnium chloride (1.0mmol) were charged into a reactor, 50mL of dichloromethane was added, and the mixture was stirred at room temperature until the reaction was completed. After the reaction is finished, a crude product obtained by concentrating the reaction liquid by a rotary evaporator is subjected to column chromatography separation by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1 to obtain pure 3db with the yield of 84%.
The nuclear magnetic data for 3db are as follows:
1H NMR(500MHz,DMSO-d6)δ7.65(d,J＝8.0Hz,1H),7.58(d,J＝1.5Hz,1H),7.45-7.39(m,5H),7.34-7.32(m,1H),6.08(d,J＝4.5Hz,1H),4.26(d,J＝5.0Hz,1H),3.73(s,3H),1.51(s,3H)ppm.
13C NMR(125MHz,DMSO-d6)δ161.34,144.71,144.38,140.16,133.63,131.37,131.03,129.86(d,J＝19.5Hz),128.73(d,J＝6.3Hz),128.40,128.20,112.01,106.69,52.20,42.22,16.63ppm.
example 5
The reaction equation is as follows:
under nitrogen protection, compound 1d (5mmol), 2c (10mmol) and hafnium chloride (1.0mmol) were charged into a reactor, 50mL of dichloromethane was added, and the mixture was stirred at room temperature until the reaction was completed. After the reaction is finished, a crude product obtained by concentrating the reaction liquid by a rotary evaporator is subjected to column chromatography separation by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1 to obtain pure 3dc with the yield of 63%.
Nuclear magnetic data for 3dc are as follows:
1H NMR(500MHz,DMSO-d6)δ8.07(s,1H),7.93(d,J＝8.0Hz,1H),7.89(d,J＝8.5Hz,1H),7.62-7.59(m,3H),7.54(t,J＝7.5Hz,1H),7.45-7.37(m,3H),6.92-6.86(m,5H),6.34(d,J＝4.5Hz,1H),4.97(s,1H),3.69(s,3H)ppm.
13C NMR(125MHz,DMSO-d6)δ161.13,146.39,144.39,140.00,137.04,132.94,131.44,131.24,131.02,130.14,129.67,129.27,129.10,128.71,128.32(d,J＝4.5Hz),127.76,126.89,126.77,126.13,125.15,124.94,114.88,113.54,52.27,42.03ppm.
example 6
The reaction equation is as follows:
under nitrogen protection, compound 1d (5mmol), 2d (20mmol) and hafnium chloride (1.0mmol) were charged into a reactor, 50mL of dichloromethane was added, and the mixture was stirred at room temperature until the reaction was completed. After the reaction is finished, a crude product obtained by concentrating the reaction liquid by a rotary evaporator is subjected to column chromatography separation by using a mixed solvent of petroleum ether and ethyl acetate with the volume ratio of 50:1 to obtain pure 3dd with the yield of 72%.
Nuclear magnetic data for 3dd are as follows:
1H NMR(500MHz,DMSO-d6)δ7.57(d,J＝8.5Hz,1H),7.50(d,J＝1.5Hz,1H),7.30-7.28(m,1H),7.18(d,J＝9.0Hz,2H),6.82(dd,J＝14.5,9.0Hz,4H),6.68(d,J＝8.5Hz,2H),6.23(d,J＝5.0Hz,1H),4.64(d,J＝5.0Hz,1H),3.75(s,3H),3.71(s,3H),3.63(s,3H)ppm.
13C NMR(125MHz,DMSO-d6)δ161.26,159.15,157.90,146.40,144.80,139.82,131.25-130.992(m),130.31(d,J＝5.8Hz),129.89,129.56,128.47(d,J＝4.4Hz),127.78,126.14,113.60(d,J＝13.4Hz),113.33,110.66,55.03,54.80,52.28,42.59,30.70ppm.
as can be seen from the above examples, the multi-substituted 4H-pyrans can be synthesized in a diversified and efficient manner according to the present invention.
Claims (7)
1. A method for synthesizing polysubstituted 4H-pyran compounds, wherein the 4H-pyran compounds have a structure shown in formula I:
wherein R is1Selected from any one of saturated alkyl, substituted alkyl, aryl, substituted aryl, naphthyl and thienyl；
R2Any one selected from methyl, ethyl and isopropyl;
R3、R4selected from any two of saturated alkyl, substituted alkyl, aryl, substituted aryl, naphthyl and thienyl which are the same or different;
the substituent of the substituted alkyl and the substituted aryl is any one of halogen atom, saturated alkyl, aryl, ester group, trifluoromethyl, nitro, hydroxyl and alkoxy;
the method comprises the following steps: under the protection of nitrogen, sequentially adding beta, gamma-unsaturated-alpha-keto ester, alkyne, Lewis acid and a solvent into a reactor, stirring at a certain temperature until the reaction is finished, and performing column chromatography separation to obtain a polysubstituted 4H-pyran compound, wherein the chemical process is shown as a reaction formula II:
2. the preparation method according to claim 1, wherein the Lewis acid is any one different from iron bromide, hafnium chloride, indium bromide and indium triflate.
3. The production method according to claim 1, wherein the solvent is any one selected from dichloromethane, chloroform, 1, 2-dichloroethane, tetrahydrofuran, toluene, and acetonitrile.
4. The preparation method according to claim 1, wherein the molar ratio of the beta, gamma-unsaturated-alpha-ketoester, alkyne, Lewis acid is 1.0 (1.0-10.0) to (0.05-0.3).
5. The process according to claim 1, wherein the reaction time is 0.5 to 6 hours.
6. The production method according to claim 1, wherein the reaction temperature is 0 to 60 ℃.
7. The preparation process according to claim 1, wherein the column chromatography is carried out using a mixed solvent of petroleum ether and ethyl acetate.
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| CN104592181A (en) * | 2015-01-29 | 2015-05-06 | 华东师范大学 | 2-fluoro-polysubstituted-4H-pyran derivatives and preparation method thereof |
| CN107216300A (en) * | 2017-05-22 | 2017-09-29 | 中国科学院化学研究所 | The method of synthesis of chiral dihydropyran cyclics |
-
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- 2021-12-20 CN CN202111565733.6A patent/CN114181182B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104592181A (en) * | 2015-01-29 | 2015-05-06 | 华东师范大学 | 2-fluoro-polysubstituted-4H-pyran derivatives and preparation method thereof |
| CN107216300A (en) * | 2017-05-22 | 2017-09-29 | 中国科学院化学研究所 | The method of synthesis of chiral dihydropyran cyclics |
Non-Patent Citations (5)
| Title |
|---|
| ABDELKEBIR JELLAL 等: "Ethylenic acyl cyanides II: Conjugate addition of alkynylsilanes to ethylenic acyl cyanides", 《TETRAHEDRON LETTERS》, vol. 24, no. 13, pages 1395 - 1398 * |
| DEPENG DUAN 等: "HfCl4-Catalyzed [4 + 2] Cycloaddition of β,γ-Unsaturated α-Keto Esters with Alkynes", 《J. ORG. CHEM.》, vol. 87, pages 5188 * |
| ICHIRO KOYAMA 等: "Nickel-Catalyzed [4 + 2] Cycloaddition of Enones with Alkynes", 《J. AM. CHEM. SOC.》, vol. 131, pages 1350 - 1351 * |
| JACQUELINE FICINI 等: "Synthèse d\'amino-2 alcoxy-6 γ pyrannes et de carbométhoxycyclobutanones par cycloaddition d\'une ynamine sur les esters α-β éthyléniques", 《TETRAHEDRON LETTERS》, vol. 11, pages 885 - 888 * |
| 吕健;钟兴仁;程津培;罗三中;: "不对称双酸催化3,4-二氢-2H-吡喃的反电子Hetero-Diels-Alder反应", 化学学报, no. 14, pages 1518 - 1522 * |
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