CN111423405A - Method for synthesizing benzopyran 3 alcohol derivative compound - Google Patents
Method for synthesizing benzopyran 3 alcohol derivative compound Download PDFInfo
- Publication number
- CN111423405A CN111423405A CN201911220207.9A CN201911220207A CN111423405A CN 111423405 A CN111423405 A CN 111423405A CN 201911220207 A CN201911220207 A CN 201911220207A CN 111423405 A CN111423405 A CN 111423405A
- Authority
- CN
- China
- Prior art keywords
- hydrogen
- benzopyran
- solvent
- compound
- halogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrane Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to the technical field of compound preparation, and discloses a method for synthesizing benzopyran 3 alcohol derivative compounds, which comprises the following steps: (1) mixing the compound I with a palladium catalyst, an oxidant and a solvent, and carrying out closed stirring reaction for 1-24 h at the temperature of 70-130 ℃; carrying out post-treatment on the mixed solution obtained in the step (1) to obtain an intermediate product II; mixing the intermediate product II with a catalyst, acetonitrile and water, replacing air with nitrogen, and carrying out closed stirring reaction at 85-95 ℃ for 1-24 h; and (4) carrying out post-treatment on the mixed solution obtained in the step (3) to obtain a final product III benzopyran 3 alcohol derivative compound. The invention directly carries out intramolecular C (sp) through cross dehydrogenation coupling3) the-H arylation is carried out to synthesize the benzopyran 3 alcohol derivative compound, the route is simple, the yield is high, the universality is good, the reaction condition is mild, and the selectivity is high.
Description
Technical Field
The invention relates to the technical field of compound preparation, in particular to a method for synthesizing benzopyran-3-alcohol derivative compounds.
Background
C(sp3)-C(sp2) The bond is a basic chemical bond in organic chemistry, constructionC(sp3)-C(sp2) Have long been receiving extensive attention and research. Construction of C (sp) in the prior art3)-C(sp2) The key method mainly comprises the following steps: 1. Friedel-Crafts reaction, but the method has relatively poor regioselectivity and narrow substrate application range, so the method limits the application of the method in the later functionalization of aromatic hydrocarbon (especially mono-substituted aromatic hydrocarbon) to some extent. 2. Construction of C (sp) by transition metal catalyzed cross-coupling reaction3)-C(sp2) Keys, for example: although these methods are widely used, they usually require two cross-coupled moieties for pre-functionalization, by Suzuki-Miyama coupling, Negishi arylation, Kumada reaction and Hiyama reaction, among others. And direct cross-coupling reaction to construct C (sp)3)-C(sp2) The manner of bonding has not been extensively studied at present.
Benzopyran-3-ol derivatives have various biological activities such as analgesic, anticancer, antibacterial, antioxidant, etc., and are widely present in various bioactive compounds, for example: antioxidant and antibacterial catechin (Epicatechin) and chromancalin (Cromakalim) for treating hypertension, angina pectoris and asthma contain benzopyran-3-ol derivative skeleton structure. The methods for synthesizing benzopyran-3-ol derivatives reported in the prior art, such as CN105219815A and CN 1214675 disclosed in Chinese patent literature, generally adopt the above-mentioned method for constructing C (sp) in benzopyran-3-ol derivatives3)-C(sp2) The bond method has the defects of difficult obtainment of reaction raw materials, low yield of key intermediates, harsh reaction conditions and the like. Therefore, a method for synthesizing benzopyran-3-alcohol derivative compounds with simple route, higher yield and good universality is needed to be found.
Disclosure of Invention
The invention aims to solve the problems of difficult obtainment of reaction raw materials, low yield of key intermediates and harsh reaction conditions of the synthetic method of the benzopyran-3-alcohol derivative compounds in the prior art, and provides a method for synthesizing the benzopyran-3-alcohol derivative compounds by directly carrying out cross dehydrogenation couplingIntramolecular C (sp)3) The benzopyran-3-alcohol derivative compound is synthesized by-H arylation, and has the advantages of simple route, higher yield, good universality, mild reaction conditions and high selectivity.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) mixing a compound I with a palladium catalyst, an oxidant and a solvent, and carrying out closed stirring reaction for 1-24 hours at the temperature of 70-130 ℃, wherein the structural formula of the compound I is as follows:
wherein R is1、R2、R3、R4、R5、R6、R7、R8、R9Respectively selecting one from hydrogen, C1-C6 straight chain or branched chain aliphatic alkyl, C1-C6 alkoxy, halogen and C6-C10 aryl, wherein the halogen is selected from one from F, Cl, Br and I;
(2) carrying out post-treatment on the mixed solution obtained in the step (1) to obtain an intermediate product II;
(3) mixing the intermediate product II with a catalyst, acetonitrile and water, replacing air with nitrogen, and carrying out closed stirring reaction at 85-95 ℃ for 1-24 h;
(4) and (4) carrying out post-treatment on the mixed solution obtained in the step (3) to obtain a final product III benzopyran-3-alcohol derivative compound.
The invention firstly adopts the mode of cross dehydrogenation coupling to directly carry out intramolecular C (sp) on the compound I through the steps (1) and (2)3) -H arylation to give intermediate II of formula:
then, the guiding group in the intermediate product II is replaced by hydrogen through the steps (3) and (4), and finally, a final product III with the structural formula as follows is obtained:
the structural formula shows that the final product III is the benzopyran-3-alcohol derivative compound. The benzopyran-3-alcohol derivative compound is prepared by directly arylating in a cross dehydrogenation coupling mode, and the method has the advantages of simple route, higher yield, good universality, mild reaction conditions and high selectivity.
Preferably, R in the compound I1Is one of hydrogen and C1-C6 straight chain or branched chain fatty alkyl; r2Is one of hydrogen, halogen, straight chain or branched chain aliphatic alkyl of C1-C6, aryl of C6-C10 and aromatic acyl; r3Is one of hydrogen, C1-C6 straight chain or branched chain aliphatic alkyl, C1-C6 alkoxy and halogen; r4Is one of hydrogen and halogen; r5Is one of hydrogen, halogen, C1-C6 straight chain or branched chain aliphatic alkyl or R5And R6To form a pyridine ring; r6Is one of hydrogen, halogen and trifluoromethyl or R5And R6To form a pyridine ring; r7Is one of hydrogen, C1-C6 straight chain or branched chain aliphatic alkyl, halogen and trifluoromethyl; r8Is one of hydrogen, halogen and trifluoromethyl; r9Is one of hydrogen, halogen and C1-C6 straight chain or branched chain fatty alkyl.
Most preferably, R1Is hydrogen or methyl; r2Is one of hydrogen, methyl, fluorine, chlorine, bromine, phenyl and benzoyl; r3Is one of hydrogen, methyl and chlorine; r4Is hydrogen or bromine; r5Is one of hydrogen, fluorine and methyl or R5And R6To form a pyridine ring; r6Is one of hydrogen, fluorine and trifluoromethyl or R5And R6To form a pyridine ring; r7Is one of hydrogen, methyl, fluorine and trifluoromethyl; r8Is one of hydrogen, fluorine and trifluoromethyl; r9Is one of hydrogen, fluorine and methyl.
Preferably, in step (1), the palladium catalyst is selected from one of palladium acetate, palladium dichloride, palladium trifluoroacetate, bis (benzonitrile) palladium dichloride, tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium, tetrakis (triphenylphosphine) palladium and bis (triphenylphosphine) palladium dichloride, and the ratio of the amount of compound I to the amount of palladium catalyst material is 1: (0.05-0.15).
More preferably, in the step (1), the palladium catalyst is palladium acetate, and the ratio of the amount of the compound I to the amount of the palladium catalyst substance is 1 (0.05-0.1).
Preferably, in the step (1), the oxidizing agent is selected from one of iodobenzene acetate, potassium persulfate, tert-butyl hydroperoxide, N-fluoro-bis-benzenesulfonamide and Selectfluor, and the ratio of the amount of the compound I to the oxidizing agent is 1: (1.0-3.0).
More preferably, the oxidizing agent in step (1) is N-fluorobisbenzenesulfonamide, and the ratio of the amount of the substance of compound I to the oxidizing agent is 1: (1.0-2.0).
Preferably, in the step (1), the solvent is one selected from toluene, trifluorotoluene, chlorobenzene, xylene, nitromethane, acetic acid, ethyl acetate, 1, 2-dichloroethane, acetonitrile, chloroform, tetrahydrofuran, 1, 4-dioxane, N-hexane and N, N-dimethylformamide, and the volume of the solvent is 0.5-5 m L/mmol based on the substance of the compound I.
More preferably, the solvent in the step (1) is 1, 2-dichloroethane, and the volume usage amount of the solvent is 0.75-2 m L/mmol.
Preferably, the reaction temperature in the step (1) is 75 to 90 ℃.
Preferably, the reaction time in the step (1) is 4-24 h, and more preferably 6-24 h.
Preferably, the post-treatment method in step (2) is: adding ethyl acetate into the mixed solution obtained in the step (1) for dilution, filtering, distilling the filtrate under reduced pressure to remove the solvent, separating the residue by column chromatography, taking the mixed solution of petroleum ether and ethyl acetate as an eluent, collecting the eluent containing the product, and distilling the eluent to remove the solvent to obtain an intermediate product II.
Preferably, the catalyst in the step (3) is molybdenum hexacarbonyl, and the mass ratio of the intermediate product II to the catalyst is 1 (1.0-5.0).
More preferably, the ratio of the amount of the intermediate product II to the amount of the catalyst substance in the step (3) is 1 (1.0 to 2.0).
Preferably, in the step (3), the volume usage of acetonitrile is 1-5 m L/mmol and the volume usage of water is 1-10 rops/mmol based on the mass of the intermediate product II.
More preferably, in the step (3), the volume usage of acetonitrile is 1-3 m L/mmol and the volume usage of water is 2-8 rops/mmol based on the mass of the intermediate product II.
Preferably, the reaction time in the step (3) is 12-24 h.
Preferably, the post-treatment method in step (4) is: and (3) distilling the mixed solution obtained in the step (3) under reduced pressure to remove the solvent, adding water, extracting with ethyl acetate, drying the organic phase, distilling under reduced pressure to remove the solvent, separating the residue by column chromatography, collecting the eluent containing the product by taking the mixed solution of petroleum ether and ethyl acetate as an eluent, and evaporating the eluent to remove the solvent to obtain the final product III.
Therefore, the beneficial effects of the invention are as follows: the benzopyran-3-alcohol derivative compound is prepared by adopting the following technical route, and has the advantages of simple route, higher yield, good universality, mild reaction conditions and high selectivity:
drawings
FIG. 1 is a drawing of intermediate II of example 11HNMR spectrogram;
FIG. 2 is a drawing of intermediate II of example 113CNMR spectrogram;
FIG. 3 is the intermediate II of example 21HNMR spectrogram;
FIG. 4 is the intermediate II of example 213CNMR spectrogram;
FIG. 5 is a drawing of intermediate II of example 31HNMR spectrogram;
FIG. 6 is intermediate II of example 313CNMR spectrogram;
FIG. 7 is the intermediate II of example 41HNMR spectrogram;
FIG. 8 is the intermediate product II of example 413CNMR spectrogram;
FIG. 9 is a drawing of intermediate II of example 51HNMR spectrogram;
FIG. 10 is the intermediate product II of example 513CNMR spectrogram;
FIG. 11 is intermediate II of example 61HNMR spectrogram;
FIG. 12 is intermediate II of example 613CNMR spectrogram;
FIG. 13 is intermediate II of example 71HNMR spectrogram;
FIG. 14 is a drawing of intermediate II of example 713CNMR spectrogram;
FIG. 15 is of intermediate II of example 81HNMR spectrogram;
FIG. 16 is the intermediate product II of example 813CNMR spectrogram;
FIG. 17 is intermediate II of example 91HNMR spectrogram;
FIG. 18 is intermediate II of example 913CNMR spectrogram.
Detailed Description
The invention is further described with reference to the following detailed description and accompanying drawings. The structural formula of the compound I in each embodiment of the invention is as follows:
wherein R is5、R7、R9Is hydrogen, R6And R8Is trifluoromethyl to form a guide group DG of the formulaAl：
That is, the structural formula of compound I in the examples of the present invention is:
example 1:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (134.4mg, 0.3mmol), palladium acetate (3.4mg, 0.015mmol), N-fluorobis (benzenesulfonamide) (0.142g, 0.45mmol), 1, 2-dichloroethane (3m L) were charged into a closed reaction vessel, and the mixture was stirred at 90 ℃ for 24 hours while being closed, whereby R in compound I was1、R2、R3、R4Are all hydrogen;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 85.6mg of an intermediate product II (yield 64%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
White solid；1H NMR(500MHz,CDCl3)＝8.61(s,1H),8.04(s,2H),7.62(s,1H),7.21-7.11(m,2H),6.96(td,J1＝7.4Hz,J2＝1.2Hz,1H),6.89(dd,J1＝8.2Hz,J2＝1.2Hz,1H),4.88-4.84(m,1H),4.39(ddd,J1＝11.6Hz,J2＝4.8Hz,J3＝1.9Hz,1H),4.30(d,J＝11.7Hz,1H),3.34-3.25(m,1H),3.15-3.07(m,1H),2.11(s,3H)ppm；13C NMR(126MHz,CDCl3)＝161.0,154.2,151.4,138.7,132.4(q,J＝33.5Hz,2C),129.8,127.7,123.1(q,J＝273.3Hz,2C),121.2,119.4(s,2C),119.4,117.5(dt,J1＝7.7Hz,J2＝3.9Hz),116.6,75.3,67.1,29.8,9.7ppm；HRMS(ESI-TOF):calcd.[M+Na]+469.0957；found:469.0955.
from the above data and FIGS. 1 and 2, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (44.6mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100-200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 10.7mg of a final product III (yield 71%), and obtaining the final product III which is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate II.
Example 2:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (138.6mg, 0.3mmol), palladium chloride (5.4mg, 0.03mmol), N-fluorobis-benzenesulfonamide (0.142g, 0.45mmol), 1, 2-dichloroethane (3m L) were charged into a closed reaction vessel, and the reaction was stirred at 90 ℃ for 24 hours while sealing, whereby R in compound I was1、R3、R4Are each hydrogen, R2Is methyl;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 114.5mg of an intermediate product II (yield 83%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.64(s,1H),8.05(s,2H),7.63(s,1H),6.99-6.92(m,2H),6.79(d,J＝8.2Hz,1H),4.85-4.82(m,1H),4.35(ddd,J1＝11.5Hz,J2＝4.9Hz,J3＝1.9Hz,1H),4.27(d,J＝11.6Hz,1H),3.25(dd,J1＝17.1Hz,J2＝5.6Hz,1H),3.06(dd,J1＝16.8Hz,J2＝3.6Hz,1H),2.29(s,3H),2.11(s,3H)ppm；13C NMR(126MHz,CDCl3)＝161.0,152.0,151.4,138.8,132.4(q,J＝33.5Hz,2C),130.5,130.2,128.3,123.1(q,J＝273.3Hz,2C),119.4(d,J＝3.7Hz,2C),119.0,118.1-117.0(m),116.3,75.5,67.1,29.8,20.5,9.7ppm；HRMS(ESI-TOF):calcd.[M+Na]+483.1114；found:483.1113.
from the above data and FIGS. 3 and 4, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (46.0mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100-200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 12.1mg of a final product III (yield 74%), and obtaining the final product III which is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate product II.
Example 3:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (157.2mg, 0.3mmol), palladium acetate (6.8mg, 0.03mmol), selectfluor (0.159g, 0.45mmol), 1, 2-dichloroethane (3m L) were charged into a closed reaction vessel, and R in compound I, R in which R is in the form of a salt, was reacted at 90 ℃ for 24 hours with stirring in a closed state1、R3、R4Are each hydrogen, R2Is phenyl;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 134.7mg of an intermediate product II (yield 86%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.75(s,1H),8.11(s,2H),7.64(s,1H),7.56(d,J＝7.0Hz,2H),7.47-7.39(m,3H),7.36(d,J＝2.3Hz,1H),7.33(t,J＝7.4Hz,1H),6.97(d,J＝8.4Hz,1H),4.91-4.87(m,1H),4.43(ddd,J1＝11.5Hz,J2＝5.0Hz,J3＝1.7Hz,1H),4.35(d,J＝11.2Hz,1H),3.35(dd,J1＝16.9Hz,J2＝5.3Hz,1H),3.17(dd,J1＝17.0Hz,J2＝4.7Hz,1H),2.13(s,3H)ppm；13C NMR(126MHz,CDCl3)＝160.9,153.6,151.7,140.6,138.7,134.4,132.5(q,J＝33.6Hz,2C),128.8(s,2C),128.5,126.8,126.7(s,2C),126.5,123.1(q,J＝273.4Hz,2C),119.4(d,J＝3.8Hz,2C),119.2,117.6(t,J＝3.9Hz),117.0,75.4,67.0,29.9,9.8ppm；HRMS(ESI-TOF):calcd.[M+Na]+545.1270；found:545.1270.
from the above data and FIGS. 5 and 6, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (52.2mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100 meshes and 200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 18.5mg of a final product III (yield is 82%), and obtaining the final product III which is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate product II.
Example 4:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (139.8mg, 0.3mmol), palladium acetate (6.8mg, 0.03mmol), N-fluorobisbenzenesulfonamide (0.142g, 0.45mmol), 1, 2-dichloroethane (3m L) were charged in a closed reaction vessel and the temperature was controlled at 90 deg.CStirring in a closed environment for reaction for 24 hours, and obtaining R in the compound I1、R3、R4Are each hydrogen, R2Is fluorine;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 114.1mg of an intermediate product II (yield 82%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.69(s,1H),8.08(s,2H),7.63(s,1H),6.88-6.81(m,3H),4.85-4.82(m,1H),4.38(ddd,J1＝11.6Hz,J2＝4.8Hz,J3＝1.9Hz,1H),4.26(d,J＝11.6Hz,1H),3.26(dd,J1＝17.0Hz,J2＝5.4Hz,1H),3.08(dd,J1＝17.1Hz,J2＝4.2Hz,1H),2.10(s,3H)ppm；13C NMR(126MHz,CDCl3)＝160.9,157.2(d,J＝239.2Hz),151.8,150.1(d,J＝2.2Hz),138.7,132.5(q,J＝33.5Hz,2C),123.1(q,J＝273.3Hz,2C),120.3(d,J＝7.6Hz),119.4(d,J＝4.0Hz,2C),117.7-117.5(m),117.5,115.7(d,J＝23.0Hz),114.5(d,J＝23.2Hz),75.0,66.9,29.9,9.8ppm；HRMS(ESI-TOF):calcd.[M+Na]+487.0863；found:487.0863.
from the above data and FIGS. 7 and 8, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (46.4mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100-200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 13.9mg of a final product III (yield is 83%), and knowing the structure of the intermediate product II, the final product III is a benzopyran-3-alcohol derivative compound.
Example 5:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) a closed reaction vessel was charged with compound I (165.6mg, 0.3mmol), palladium acetate (6.8mg, 0.03mmol), N-fluorobisphenylsulfonamide (0.142g, 0.45mmol), 1, 2-dichloroethane (3m L), and the mixture was stirred under a closed condition at 75 ℃ for 24 hours, wherein R in compound I1、R3、R4Are each hydrogen, R2Is benzoyl;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-200 meshes; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 140.2mg of an intermediate product II (yield is 85%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.84(s,1H),8.12(s,2H),7.76(d,J＝7.0Hz,2H),7.69(d,J＝2.0Hz,1H),7.64(d,J＝8.3Hz,2H),7.58(t,J＝7.5Hz,1H),7.48(t,J＝7.6Hz,2H),6.92(d,J＝8.5Hz,1H),4.88(dd,J1＝4.7Hz,J2＝2.2Hz,1H),4.50(ddd,J1＝11.7Hz,J2＝4.7,J3＝2.0Hz,1H),4.35(d,J＝11.7Hz,1H),3.29(dd,J1＝17.0Hz,J2＝5.0Hz,1H),3.15(dd,J1＝17.1Hz,J2＝3.1Hz,1H),2.09(s,3H)ppm；13C NMR(126MHz,CDCl3)＝195.6,160.8,157.9,152.0,138.7,138.1,132.8,132.4(q,J＝33.6Hz,2C),132.0,130.7,130.6,129.7(s,2C),128.2(s,2C),123.0(q,J＝273.3Hz,2C),119.4(d,J＝3.7Hz,2C),118.9,118.0-117.4(m),116.3,74.7,67.1,29.6,9.9ppm；HRMS(ESI-TOF):calcd.[M+Na]+573.1219；found:573.1221.
from the above data and FIGS. 9 and 10, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (55.0mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100 meshes and 200 meshes; separating and purifying the residue by using V (petroleum ether)/V (ethyl acetate) ═ 3/1], collecting eluent containing the product, and evaporating the eluent to remove the solvent to obtain 20.6mg of a final product III (yield 81%), wherein the final product III is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate II.
Example 6:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (144.6mg, 0.3mmol), palladium acetate (6.8mg, 0.03mmol), N-fluorobis-benzenesulfonamide (0.142g, 0.45mmol), toluene (3m L) were added to a closed reaction vessel, and R in compound I, which is R in compound I, was reacted at 90 ℃ for 24 hours with stirring in a closed state1、R2、R4Are each hydrogen, R3Is chlorine;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, decompressing and removing the solvent, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 118.1mg of an intermediate product II (yield 82%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.65(s,1H),8.07(s,2H),7.63(s,1H),7.12(t,J＝8.1Hz,1H),7.04(d,J＝8.0Hz,1H),6.83(d,J＝8.3Hz,1H),4.93-4.86(m,1H),4.40(ddd,J1＝11.7Hz,J2＝4.7Hz,J3＝1.8Hz,1H),4.25(d,J＝11.7Hz,1H),3.22(dd,J1＝17.9Hz,J2＝5.7Hz,1H),3.14(dd,J1＝17.8Hz,J2＝2.6Hz,1H),2.12(s,3H)ppm；13C NMR(126MHz,CDCl3)＝160.8,155.3,151.8,138.7,134.7,132.5(q,J＝33.6Hz,2C),127.9,123.1(q,J＝273.2Hz,2C),121.8,119.4(d,J＝4.1Hz,2C),118.3,118.0-117.1(m),115.3,74.9,66.7,28.3,9.8ppm；HRMS(ESI-TOF):calcd.[M+Na]+503.0568；found:503.0568.
from the above data and FIGS. 11 and 12, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (48.0mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100 meshes and 200 meshes; separating and purifying with V (petroleum ether)/V (ethyl acetate) ═ 3/1], collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 14.7mg of a final product III (yield 80%), and obtaining the final product III which is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate product II.
Example 7:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (157.8mg, 0.3mmol), palladium acetate (6.8mg, 0.03mmol), N-fluorobis-benzenesulfonamide (0.142g, 0.45mmol), 1, 2-dichloroethane (4.5m L) were charged into a closed reaction vessel, and R in compound I was reacted under stirring at 90 ℃ for 24 hours under closed conditions1、R2、R3Are each hydrogen, R4Is bromine;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 127.3mg of an intermediate product II (yield 81%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.64(s,1H),8.07(s,2H),7.63(s,1H),7.42(d,J＝8.0Hz,1H),7.07(d,J＝7.6Hz,1H),6.82(t,J＝7.7Hz,1H),4.88-4.85(m,1H),4.52(ddd,J1＝11.7Hz,J2＝4.8Hz,J3＝1.9Hz,1H),4.39(d,J＝11.2Hz,1H),3.30(dd,J1＝17.3Hz,J2＝4.6Hz,1H),3.12(dd,J1＝17.0Hz,J2＝3.3Hz,1H),2.10(s,3H)ppm；13C NMR(126MHz,CDCl3)＝160.8,151.8,150.7,138.7,132.5(q,J＝33.5Hz,2C),131.5,129.0,123.1(q,J＝273.4Hz,2C),121.9,120.9,119.4(d,J＝3.8Hz,2C),117.8-117.3(m),110.7,74.9,67.7,30.0,9.8ppm；HRMS(ESI-TOF):calcd.[M+Na]+547.0062；found:547.0059.
from the above data and fig. 13 and 14, it can be seen that the structure of intermediate II is:
(3) adding the intermediate product II (52.4mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100-200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 17.5mg of a final product III (yield 77%), and obtaining the final product III which is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate II.
Example 8:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) a closed reaction vessel was charged with Compound I (153.0mg, 0.3mmol), Palladium acetate (6.8mg, 0.03mmol), N-Fluoro-diphenyl sulfonamide (0.190g, 0.6mmol) and 1, 2-dichloroethane (3m L) are reacted at 90 ℃ for 24h under sealed stirring, R in the compound I1And R3Is methyl, R2Is chlorine, R4Is hydrogen;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-200 meshes; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 129.5mg of an intermediate product II (yield 85%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.75(s,1H),8.11(s,2H),7.64(s,1H),6.68(s,1H),4.88-4.85(m,1H),4.30(ddd,J1＝11.3Hz,J2＝5.3Hz,J3＝1.6Hz,1H),4.22(dd,J1＝11.3Hz,J2＝1.4Hz,1H),3.12(dd,J1＝17.1Hz,J2＝5.8Hz,1H),2.94(dd,J1＝17.1Hz,J2＝4.8Hz,1H),2.34(d,J＝6.1Hz,6H),2.12(s,3H)ppm；13C NMR(126MHz,CDCl3)＝160.9,152.2,151.8,138.7,135.4,135.2,132.5(q,J＝33.6Hz,2C),127.1,123.1(q,J＝273.3Hz,2C),119.4(d,J＝4.1Hz,2C),118.4-117.4(m),116.7,116.4,75.6,66.2,28.8,20.8,16.3,9.9ppm；HRMS(ESI-TOF):calcd.[M+Na]+531.0881；found:531.0875.
from the above data and FIGS. 15 and 16, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (50.8mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100-200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 16.7mg of a final product III (yield 79%), wherein the final product III is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate product II.
Example 9:
a method for synthesizing benzopyran-3-alcohol derivative compounds comprises the following steps:
(1) compound I (144.6mg, 0.3mmol), palladium acetate (6.8mg, 0.03mmol), N-fluorobis-benzenesulfonamide (0.142g, 0.45mmol), 1, 2-dichloroethane (3m L) were charged into a closed reaction vessel, and the reaction was stirred at 90 ℃ for 24 hours while sealing, whereby R in compound I was1、R3、R4Are each hydrogen, R2Is chlorine;
(2) diluting the mixed solution obtained in the step (1) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, separating and purifying the residue by column chromatography [ GF254 silica gel; 100-mesh 200-mesh; developing solvent V (petroleum ether)/V (ethyl acetate) ═ 50/1], collecting eluent containing the product, and evaporating the solvent from the eluent to obtain 121.0mg of an intermediate product II (yield 84%);
the intermediate product II obtained was subjected to structural analysis, and the results were as follows:
1H NMR(500MHz,CDCl3)＝8.69(s,1H),8.09(s,2H),7.64(s,1H),7.11(dd,J1＝10.2Hz,J2＝1.7Hz,2H),6.81(d,J＝8.4Hz,1H),4.85-4.82(m,1H),4.40(ddd,J1＝11.7Hz,J2＝4.7Hz,J3＝2.0Hz,1H),4.27(d,J＝11.5Hz,1H),3.24(dd,J1＝17.7Hz,J2＝4.8Hz,1H),3.07(dd,J1＝17.3Hz,J2＝2.8Hz,1H),2.10(s,3H)ppm；13C NMR(126MHz,CDCl3)＝160.8,152.7,151.9,138.8,132.5(q,J＝33.6Hz,2C),129.4,127.8,125.9,123.1(q,J＝273.4Hz,2C),120.6,119.4(d,J＝4.1Hz,2C),117.9,117.8-117.2(m),74.8,66.9,29.6,9.8ppm；HRMS(ESI-TOF):calcd.[M+Na]+503.0568；found:503.0565.
from the above data and FIGS. 17 and 18, it can be seen that intermediate II has the following structure:
(3) adding the intermediate product II (48.0mg, 0.1mmol), molybdenum hexacarbonyl (33mg, 0.1mmol), acetonitrile (3m L) and water (4drops) into a closed reaction vessel with the volume of 25m L, and reacting the mixture at 90 ℃ for 12 hours under the protection of nitrogen in a closed manner and with stirring;
(4) diluting the mixture obtained in the step (3) with ethyl acetate (10m L), filtering, removing the solvent under reduced pressure, performing column chromatography on the residue [ GF254 silica gel; 100-200 meshes; the developing solvent is V (petroleum ether)/V (ethyl acetate) ═ 3/1], separating and purifying, collecting eluent containing the product, evaporating the eluent to remove the solvent to obtain 14.1mg of a final product III (yield 76%), and obtaining the final product III which is a benzopyran-3-alcohol derivative compound according to the structure of the intermediate II.
As can be seen from the above examples, the benzopyran-3-alcohol derivative compound can be directly prepared by arylation in a cross dehydrogenation coupling mode by using the method of the invention, and the method has the advantages of simple route, high yield, good universality, mild reaction conditions and high selectivity.
Claims (10)
1. A method for synthesizing benzopyran-3-alcohol derivative compounds is characterized by comprising the following steps:
(1) mixing a compound I with a palladium catalyst, an oxidant and a solvent, and carrying out closed stirring reaction for 1-24 hours at the temperature of 70-130 ℃, wherein the structural formula of the compound I is as follows:
wherein R is1、R2、R3、R4、R5、R6、R7、R8、R9Respectively selecting one from hydrogen, C1-C6 straight chain or branched chain aliphatic alkyl, C1-C6 alkoxy, halogen and C6-C10 aryl, wherein the halogen is selected from one from F, Cl, Br and I;
(2) carrying out post-treatment on the mixed solution obtained in the step (1) to obtain an intermediate product II;
(3) mixing the intermediate product II with a catalyst, acetonitrile and water, replacing air with nitrogen, and carrying out closed stirring reaction at 70-130 ℃ for 1-24 h;
(4) and (4) carrying out post-treatment on the mixed solution obtained in the step (3) to obtain a final product III benzopyran-3-alcohol derivative compound.
2. The method as claimed in claim 1, wherein R in the compound I is1Is one of hydrogen and C1-C6 straight chain or branched chain fatty alkyl; r2Is one of hydrogen, halogen, straight chain or branched chain aliphatic alkyl of C1-C6, aryl of C6-C10 and aromatic acyl; r3Is one of hydrogen, C1-C6 straight chain or branched chain aliphatic alkyl, C1-C6 alkoxy and halogen; r4Is one of hydrogen and halogen; r5Is one of hydrogen, halogen, C1-C6 straight chain or branched chain aliphatic alkyl or R5And R6To form a pyridine ring; r6Is one of hydrogen, halogen and trifluoromethyl or R5And R6To form a pyridine ring; r7Is one of hydrogen, C1-C6 straight chain or branched chain aliphatic alkyl, halogen and trifluoromethyl; r8Is one of hydrogen, halogen and trifluoromethyl; r9Is one of hydrogen, halogen and C1-C6 straight chain or branched chain fatty alkyl.
3. A process for the synthesis of benzopyran-3-ol derivatives, as claimed in claim 1 or 2, wherein R is1Is hydrogen or methyl; r2Is one of hydrogen, methyl, fluorine, chlorine, bromine, phenyl and benzoyl; r3Is one of hydrogen, methyl and chlorine; r4Is hydrogen or bromine; r5Is one of hydrogen, fluorine and methyl or R5And R6To form a pyridine ring; r6Is one of hydrogen, fluorine and trifluoromethyl or R5And R6To form a pyridine ring; r7Is one of hydrogen, methyl, fluorine and trifluoromethyl; r8Is one of hydrogen, fluorine and trifluoromethyl; r9Is one of hydrogen, fluorine and methyl.
4. The method according to claim 1, wherein the palladium catalyst in step (1) is selected from one of palladium acetate, palladium dichloride, palladium trifluoroacetate, bis (benzonitrile) palladium dichloride, tris (dibenzylideneacetone) dipalladium, bis (dibenzylideneacetone) palladium, tetrakis (triphenylphosphine) palladium and bis (triphenylphosphine) palladium dichloride, and the ratio of the amount of the compound I to the amount of the palladium catalyst material is 1: (0.05-0.15).
5. The method for synthesizing benzopyran-3-ol derivatives according to claim 1, wherein in the step (1), the oxidizing agent is selected from one of iodobenzene acetate, potassium persulfate, tert-butyl hydroperoxide, N-fluoro-bis-benzenesulfonamide and Selectfluor, and the ratio of the amount of the compound I to the oxidizing agent is 1: (1.0-3.0).
6. The method for synthesizing benzopyran-3-ol derivative compounds according to claim 1, wherein the solvent in step (1) is one selected from toluene, trifluorotoluene, chlorobenzene, xylene, nitromethane, acetic acid, ethyl acetate, 1, 2-dichloroethane, acetonitrile, chloroform, tetrahydrofuran, 1, 4-dioxane, N-hexane, and N, N-dimethylformamide, and the volume of the solvent is 0.5-5 m L/mmol based on the substance of compound I.
7. The method for synthesizing benzopyran-3-ol derivatives according to claim 1, wherein the post-treatment method in the step (2) comprises the following steps: adding ethyl acetate into the mixed solution obtained in the step (1) for dilution, filtering, distilling the filtrate under reduced pressure to remove the solvent, separating the residue by column chromatography, taking the mixed solution of petroleum ether and ethyl acetate as an eluent, collecting the eluent containing the product, and distilling the eluent to remove the solvent to obtain an intermediate product II.
8. The method for synthesizing benzopyran-3-ol derivatives according to claim 1, wherein the catalyst in step (3) is molybdenum hexacarbonyl, and the mass ratio of the intermediate product II to the catalyst is 1 (1.0-5.0).
9. The method for synthesizing benzopyran-3-ol derivatives as claimed in claim 1 or 8, wherein the volume of acetonitrile used in step (3) is 1-5 m L/mmol and the volume of water used in step (3) is 1-10 rops/mmol based on the substance of intermediate product II.
10. The method for synthesizing benzopyran-3-ol derivatives as claimed in claim 1, wherein the post-treatment method in step (4) is: and (3) distilling the mixed solution obtained in the step (3) under reduced pressure to remove the solvent, adding water, extracting with ethyl acetate, drying the organic phase, distilling under reduced pressure to remove the solvent, separating the residue by column chromatography, collecting the eluent containing the product by taking the mixed solution of petroleum ether and ethyl acetate as an eluent, and evaporating the eluent to remove the solvent to obtain the final product III.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911220207.9A CN111423405B (en) | 2019-12-03 | 2019-12-03 | Method for synthesizing benzopyran 3 alcohol derivative compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911220207.9A CN111423405B (en) | 2019-12-03 | 2019-12-03 | Method for synthesizing benzopyran 3 alcohol derivative compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111423405A true CN111423405A (en) | 2020-07-17 |
| CN111423405B CN111423405B (en) | 2021-11-26 |
Family
ID=71545837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911220207.9A Active CN111423405B (en) | 2019-12-03 | 2019-12-03 | Method for synthesizing benzopyran 3 alcohol derivative compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111423405B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1214675A (en) * | 1995-11-22 | 1999-04-21 | 视觉药品公司 | Aryl or heteroaryl amides of tetrahydronaphthalene, chroman, thiochroman and 1,2,3,4-tetrahydroquinoline carboxylic acids having retinoid-like biological activity |
| CN105219815A (en) * | 2015-11-06 | 2016-01-06 | 湖北中鑫生物科技有限公司 | A kind of preparation method of epicatechin monomers |
| CN107793387A (en) * | 2016-09-05 | 2018-03-13 | 北京大学 | The method of two C H push-tos peroxidating coupling structure Dihydrobenzofuranes framework compounds |
| CN109134306A (en) * | 2018-08-22 | 2019-01-04 | 浙江工业大学 | A kind of alkyl keto-amide and its amide oxime class compound and its preparation and application |
-
2019
- 2019-12-03 CN CN201911220207.9A patent/CN111423405B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1214675A (en) * | 1995-11-22 | 1999-04-21 | 视觉药品公司 | Aryl or heteroaryl amides of tetrahydronaphthalene, chroman, thiochroman and 1,2,3,4-tetrahydroquinoline carboxylic acids having retinoid-like biological activity |
| CN105219815A (en) * | 2015-11-06 | 2016-01-06 | 湖北中鑫生物科技有限公司 | A kind of preparation method of epicatechin monomers |
| CN107793387A (en) * | 2016-09-05 | 2018-03-13 | 北京大学 | The method of two C H push-tos peroxidating coupling structure Dihydrobenzofuranes framework compounds |
| CN109134306A (en) * | 2018-08-22 | 2019-01-04 | 浙江工业大学 | A kind of alkyl keto-amide and its amide oxime class compound and its preparation and application |
Non-Patent Citations (2)
| Title |
|---|
| BING-XIN WANG ET AL.: "Pd-catalysed selective C(sp3)–H arylation and acetoxylation of alcohols", 《CHEM. COMMUN.》 * |
| 窦言东等: "导向基团辅助的C—H 键功能化", 《化学进展》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111423405B (en) | 2021-11-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101133016B (en) | Method for producing substituted biphenyls | |
| CN113214129B (en) | Method for iodination/sulfonylation reaction of 1, 6-diene compound initiated by sulfonyl free radical | |
| Kadoh et al. | Enhanced structural variety of nonplanar N-oxyl radical catalysts and their application to the aerobic oxidation of benzylic C–H bonds | |
| CN111253208A (en) | Preparation method of 1-iodoalkyne | |
| CN108610304B (en) | Synthetic method of diaryl sultam compound | |
| CN109438317A (en) | A kind of preparation method of nitrogen-alkyl (deuteroalkyl) heteroaromatic and alkyl (deuteroalkyl) aryl ethers compounds | |
| CN105026384A (en) | Novel approach for synthesis of catechins | |
| CN111423405B (en) | Method for synthesizing benzopyran 3 alcohol derivative compound | |
| Mendoza et al. | Trialkylsilyl triflimides as easily tunable organocatalysts for allylation and benzylation of silyl carbon nucleophiles with non-genotoxic reagents | |
| CN112047871A (en) | Preparation method of indole compound | |
| CN111484436A (en) | Method for introducing isopentenyl group to C3 position of indole | |
| CN115710287A (en) | Ring-opening boronization reaction method of cyclopropane compound under condition of no metal catalysis | |
| CN109651385A (en) | A kind of preparation method of pyrans [3,2-a] carbazole compound | |
| CN114560832A (en) | Method for synthesizing dibenzofuran compound | |
| CN110294708B (en) | Preparation method of trifluoroethylselenophenanthridine and 3, 4-dihydroisoquinoline derivatives | |
| CN111393258B (en) | Method for synthesizing tetrahydronaphthalene-2-alcohol derivative compound | |
| CN108440549B (en) | Synthesis method of spiro indole compound | |
| CN107353267B (en) | A method of synthesis substituted furan | |
| CN105801333B (en) | A kind of preparation method of coronene | |
| KR101006737B1 (en) | Process for the preparation of 2-sulfonyliminoindoline using Cu catalyst | |
| JP6275378B2 (en) | Process for producing carbazoles and carbazoles produced by this process. | |
| CN113620795B (en) | Method for synthesizing benzocycloheptenone compounds | |
| CN108863751B (en) | Synthetic method of Z-type halogenated chalcone compound | |
| CN112574107B (en) | Synthesis method of atropisomeric 1-arylisoquinoline N-oxide and derivatives thereof | |
| CN113620918B (en) | Method for synthesizing spiro compounds through Lewis acid catalyzed [3+2] cycloaddition reaction |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |