CN113527177A - 2-cyanoindole-substituted gem-difluoroolefin compound and preparation method and application thereof - Google Patents
2-cyanoindole-substituted gem-difluoroolefin compound and preparation method and application thereof Download PDFInfo
- Publication number
- CN113527177A CN113527177A CN202111012397.2A CN202111012397A CN113527177A CN 113527177 A CN113527177 A CN 113527177A CN 202111012397 A CN202111012397 A CN 202111012397A CN 113527177 A CN113527177 A CN 113527177A
- Authority
- CN
- China
- Prior art keywords
- compound
- cyanoindole
- substituted
- difluoroolefin
- reaction
- 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.)
- Pending
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C07D409/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a 2-cyanoindole-substituted gem-difluoroolefin compound, a preparation method and application thereof, wherein the preparation method of the compound comprises the following steps: the 2-cyanoindole-substituted gem-difluoroolefin compound is prepared by taking trifluoromethyl indole methanol compound and trimethylsilyl cyanide as raw materials, and carrying out heating reaction in a solvent under the action of a Lewis acid catalyst and an inorganic base. The invention provides a 2-cyanoindole substituted geminal difluoroolefin compound and a preparation method thereof. The method takes the trifluoromethyl indole methanol compound and the trimethylsilyl cyanide which are easy to obtain as raw materials, does not need to use explosive diazo compounds, and has the advantages of mild reaction conditions, simple operation, high yield, wide range of reaction substrates and the like.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a 2-cyanoindole-substituted gem-difluoroolefin compound and a preparation method and application thereof.
Background
The geminal difluoroalkene compound is widely applied to the fields of medicines, pesticides, insecticides, functional materials and the like. The geminal difluoroolefin is considered as a biological isoelectric substance of a carbonyl compound, and many natural products, medicaments and the like with biological activity can remarkably enhance the physiological activity and the pharmacological activity by introducing a geminal difluoroolefin unit, for example, artemisinin derivatives containing the geminal difluoroolefin show more excellent biological activity. In addition, the geminal difluoroolefin compound is also an important organic synthesis intermediate, and can be used for synthesizing various fluorine-containing and non-fluorine-containing functional molecules, such as geminal difluoroolefin which can be conveniently converted into monofluorine-substituted olefin and difluoroalkyl-substituted functional molecules and the like.
Indole is a very important alkaloid and has wide application in the fields of pharmaceutical chemistry, organic synthesis, pesticides, functional materials and the like. On the other hand, cyano-containing compounds are not only widely found in natural products and marketable drugs which are important applications, but also have very important applications in the fields of agrochemicals, polymer materials and the like. In addition, cyano compounds are also a very important class of organic synthesis intermediates, and carboxylic acid, aldehyde, ketone, amine, amide, heterocyclic compound and the like can be prepared through functional group transformation. Therefore, the synthesis of the cyano-containing indole substituted gem-difluoro olefin compound has very important significance.
At present, the synthesis method of geminal difluoroolefin has a plurality of methods, such as the classical Wittig type reaction. However, indole-substituted gem-difluoroolefins are very rare (Angew. chem. int. Ed.2020,59, 5572-5576), and these prior art methods usually require the use of explosive azo compounds and are limited in substrate reactions, usually limited to N-alkylated electron-rich indole substrates, whereas e.g.ester groups, cyano groups with electron-withdrawing functionalities cannot react. At present, no literature report exists on a 2-cyanoindole substituted geminal difluoroolefin compound and a synthetic method thereof.
Disclosure of Invention
Based on the content, the invention provides a 2-cyanoindole-substituted gem-difluoroolefin compound, and a preparation method and application thereof, and fills the technical blank in the aspect of the 2-cyanoindole-substituted gem-difluoroolefin compound.
In one technical scheme of the invention, a 2-cyanoindole-substituted geminal difluoroolefin compound has a structural formula shown in formula (1):
wherein R is1、R2、R3Are each independently of the other R1One selected from hydrogen, halogen atom, hydroxyl, cyano, ester group, methyl, ethyl or methoxy; r2One selected from hydrogen, phenyl, halogen substituted phenyl, alkyl substituted phenyl, C1-C6 branched alkyl, benzyl or allyl; r3Is selected from one of phenyl, halogen substituted phenyl, alkyl substituted phenyl, naphthyl or thienyl.
In another embodiment of the present invention, the preparation method of the 2-cyanoindole-substituted gem-difluoroolefin compound comprises the following steps: the 2-cyanoindole-substituted gem-difluoroolefin compound is prepared by taking trifluoromethyl indole methanol compound and trimethylsilyl cyanide as raw materials, and carrying out heating reaction in a solvent under the action of a Lewis acid catalyst and an inorganic base.
The specific reaction equation is as follows:
further, the method comprises the following steps of heating the reaction process, tracking the reaction by using thin plate chromatography until the reaction is complete, and carrying out post-reaction treatment: and after the reaction is finished, cooling to room temperature, filtering to remove insoluble substances, performing rotary evaporation and concentration, performing silica gel column chromatography on the crude product through 200-300 meshes, and performing gradient elution by using a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 25: 1-5: 1 as an eluent to obtain the 2-cyanoindole-substituted gem-difluoroolefin compound.
Further, the trifluoromethyl indole methanol compound is a compound shown as a formula (2):
The mol ratio of the trifluoromethyl indole methanol compound to the trimethylsilyl cyanide is 1: 2-3.
Further, the Lewis acid catalyst is scandium trifluoromethanesulfonate, and the molar ratio of the trifluoromethyl indole methanol compound to the scandium trifluoromethanesulfonate is 1: 0.05-1: 0.2.
Further, the inorganic base is any one of calcium oxide, magnesium oxide, barium oxide, zinc oxide and aluminum oxide, and the molar ratio of the inorganic base to the trifluoromethyl indole methanol compound is 10: 1.
The purpose of adding the base in the invention is to neutralize the hydrogen fluoride generated in the reaction, thereby facilitating the reaction.
Further, the inorganic base is magnesium oxide;
further, the solvent is any one of chlorobenzene, toluene, acetonitrile or dichloroethane, and the concentration of the trifluoromethyl indole methanol compound in the solvent is 0.05-0.5 mol/L.
Furthermore, the solvent is chlorobenzene, so that the yield is optimal;
further, the heating reaction temperature is 80-140 ℃, and the heating reaction time is 6-24 h.
In the third technical scheme of the invention, the 2-cyanoindole-substituted geminal difluoroolefin compound is applied as an organic synthesis intermediate.
Further, the 2-cyanoindole-substituted gem-difluoro olefin compound and methyl thiophenol are subjected to addition reaction under the catalysis of tetramethylguanidine to synthesize the thioether compound.
Further, the 2-cyanoindole-substituted gem-difluoro olefin compound and methylthiophenol are subjected to substitution reaction under the catalysis of cobalt dichloride to synthesize the amino compound.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides a 2-cyanoindole substituted geminal difluoroolefin compound and a preparation method thereof. The method takes the trifluoromethyl indole methanol compound and the trimethylsilyl cyanide which are easy to obtain as raw materials, does not need to use explosive diazo compounds, and has the advantages of mild reaction conditions, simple operation, high yield, wide range of reaction substrates and the like.
The 2-cyanoindole-substituted gem-difluoroolefin compound has indole, gem-difluoroalkenyl and cyano functional groups, can perform various chemical transformations, and is an important organic synthesis intermediate.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:
FIG. 1 is a NMR spectrum of Compound 1a prepared in example 1 of the present invention;
FIG. 2 is a NMR spectrum of Compound 1a prepared in example 1 of the present invention;
FIG. 3 is a NMR fluorine spectrum of Compound 1a prepared in example 1 of the present invention;
FIG. 4 is a single crystal diffractogram of Compound 1a prepared in example 1 of the present invention.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The description and examples are intended to be illustrative only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including, but not limited to.
Example 1:
the reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indolylmethanol 2a (87.4mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 12 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature after the reaction is finished, filtering is carried out to remove insoluble substances, filtrate is rotated and concentrated to remove a solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 25: 1-10: 1 as an eluent, so that the target product 1a (63.1mg, white solid and yield of 75%) is obtained.
FIG. 1 is a NMR spectrum of Compound 1a prepared in this example;
FIG. 2 is a NMR spectrum of Compound 1a prepared in this example;
FIG. 3 is a NMR fluorine spectrum of Compound 1a prepared in this example;
FIG. 4 is a single crystal diffractogram of Compound 1a prepared in this example
1H NMR(600MHz,CDCl3)δ8.93(s,1H),7.73–7.30(m,7H),7.24(d,J＝8.2Hz,1H),7.13(td,J＝7.9,0.8Hz,1H)；13C NMR(151MHz,CDCl3)δ154.0(dd,J＝299.0,294.5Hz),136.7,132.6(dd,J＝4.5,3.0Hz),128.8(dd,J＝4.5,3.0Hz),128.6,127.9,126.6,125.5(d,J＝3.0Hz),121.9,121.3,120.6(dd,J＝4.5,3.0Hz),113.2,112.0,106.4,87.5(dd,J＝22.7,19.6Hz)；19F NMR(565MHz,CDCl3)δ-81.76(d,J＝22.7Hz),-85.46(d,J＝22.7Hz)；HRMS(ESI)calcd for C17H10F2N2Na[M+Na]+:303.0704；found:303.0700.
Example 2
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indole methanol 2b (91.6mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 8 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature is carried out after the reaction is finished, insoluble substances are removed by filtration, the filtrate is rotated and concentrated to remove the solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 25: 1-10: 1 as an eluent, so that the target product 1b (70.6mg, white solid, yield 80%) is obtained.
1H NMR(400MHz,CDCl3)δ8.98(s,1H),7.36–7.30(m,6H),7.22(d,J＝8.5Hz,1H),7.05(s,1H),2.37(s,3H)；13C NMR(101MHz,CDCl3)δ153.9(dd,J＝296.9,293.9Hz),135.2,132.7(dd,J＝5.1,3.0Hz),128.8(dd,J＝4.0,3.0Hz),128.6128.5,127.8,125.8(d,J＝2.0Hz),120.3,120.0(dd,J＝5.1,2.0Hz),113.5,111.7,106.2(dd,J＝3.0,2.0Hz),87.5(dd,J＝22.2,20.2Hz),21.4；19F NMR(565MHz,CDCl3)δ-82.70(d,J＝23.1Hz),-84.47(d,J＝22.9Hz)；HRMS(ESI)calcd for C18H12F2N2Na[M+Na]+:317.0861；found:317.0851。
Example 3
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indolylmethanol 2c (104.8mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 24 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature after the reaction is finished, filtering is carried out to remove insoluble substances, filtrate is rotated and concentrated to remove a solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20: 1-5: 1 as an eluent, so that a target product 1c (52.8mg, white solid, yield 52%) is obtained.
1H NMR(600MHz,CDCl3)δ9.41(s,1H),8.08–8.06(m,2H),7.45(d,J＝9.3Hz,1H),7.36–7.29(m,5H),3.90(s,3H)；13C NMR(151MHz,CDCl3)δ167.5,154.0(dd,J＝299.0,293.7Hz),139.1,132.3(dd,J＝4.6,3.0Hz),128.7(t,J＝3.5Hz),128.6,128.1,127.3,125.2(d,J＝1.9Hz),124.2,123.9,121.9(dd,J＝4.7,2.8Hz),112.6,112.1,108.0,87.0(dd,J＝22.4,20.2Hz),52.3；19F NMR(565MHz,CDCl3)δ-80.97(d,J＝21.4Hz),-84.46(d,J＝21.3Hz)；HRMS(ESI)calcd for C19H12F2N2NaO2[M+Na]+:361.0759；found:361.0746。
Example 4
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indolylmethanol 2d (96.4mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 12 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature after the reaction is finished, filtering is carried out to remove insoluble substances, filtrate is rotated and concentrated to remove a solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 20: 1-8: 1 as an eluent, so that a target product 1d (87.5mg, white solid, yield 94%) is obtained.
1H NMR(600MHz,CDCl3)δ9.06(s,1H),7.48–7.28(m,5H),7.06(d,J＝8.9Hz,1H),6.82(d,J＝1.2Hz,1H),6.78(dd,J＝8.9,1.6Hz,1H),3.84(s,3H)；13CNMR(151MHz,CDCl3)δ159.7,153.9(dd,J＝297.8,293.8Hz),138.0,132.7(dd,J＝4.5,3.0Hz),128.9(dd,J＝4.5,3.0Hz),128.5,127.9,122.0,120.9(dd,J＝4.7,3.0Hz),119.8(d,J＝2.5Hz),113.9,113.5,104.7,93.8,87.6(dd,J＝22.0,20.1Hz),55.5；19F NMR(565MHz,CDCl3)δ-81.88(d,J＝23.1Hz),-85.68(d,J＝23.0Hz)；HRMS(ESI)calcd for C18H12F2N2NaO[M+Na]+:333.0810；found:333.0802。
Example 5
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indole methanol 2e (92.8mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 12 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature is carried out after the reaction is finished, insoluble substances are removed by filtration, the filtrate is rotated and concentrated to remove the solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 20: 1-10: 1 as an eluent, so that the target product 1e (87.5mg, white solid, yield 94%) is obtained.
1H NMR(600MHz,CDCl3)δ8.92(s,1H),7.46–7.29(m,5H),7.14(dd,J＝8.9,5.2Hz,1H),7.09(dd,J＝9.0,2.1Hz,1H),6.89(td,J＝9.1,2.2Hz,1H)；13C NMR(151MHz,CDCl3)δ162.4(d,J＝245.2Hz),154.0(dd,J＝298.1,294.2Hz),137.0(d,J＝13.0Hz),132.4(dd,J＝4.3,3.3Hz),128.8(t,J＝3.5Hz),128.6,128.0,122.6(d,J＝9.8Hz),122.1,121.0,113.2,111.5(d,J＝25.4Hz),106.5,98.2(d,J＝26.6Hz),87.4(dd,J＝22.2,20.0Hz)；19F NMR(565MHz,CDCl3)δ-81.44(d,J＝21.8Hz),-85.03(d,J＝21.8Hz),-113.64–-113.69(m)；HRMS(ESI)calcd for C17H10F3N2[M+H]+:299.0791；found:299.0790。
Example 6
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indole methanol 2f (116.8mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 12 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature is carried out after the reaction is finished, insoluble substances are removed by filtration, the filtrate is rotated and concentrated to remove the solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with the volume ratio of 20: 1-10: 1 as an eluent, so that the target product 1f (105.5mg, light yellow solid, 93% yield) is obtained.
1H NMR(600MHz,CDCl3)δ8.84(s,1H),7.60(s,1H),7.58(d,J＝7.5Hz,1H),7.50(d,J＝7.7Hz,1H),7.47(t,J＝7.7Hz,1H),7.04(d,J＝8.9Hz,1H),6.84(d,J＝2.0Hz,1H),6.81(dd,J＝8.9,2.2Hz,1H),3.85(s,3H)；13C NMR(151MHz,CDCl3)δ159.8,154.2(dd,J＝298.9,295.0Hz),138.1,133.7(t,J＝3.9Hz),132.2,131.0(q,J＝32.3Hz),129.1,126.6,125.5(dd,J＝7.1,3.3Hz),124.7,124.6(q,J＝4.5Hz),122.9,121.6,121.1,119.8(t,4.2Hz),119.5(d,1.6Hz),113.8,104.8,93.9,87.1(dd,J＝21.4,20.0Hz),55.4；19F NMR(565MHz,CDCl3)δ62.70(s,3F),-79.88–-79.96(m,1F),-84.09–-84.13(m,1F)；HRMS(ESI)calcd for C19H11F5N2NaO[M+Na]+:401.0684；found:401.0680。
Example 7
The reaction equation is:
taking a 25mL round-bottom flask, sequentially adding 2g (100.6mg,0.3mmol) of trifluoromethyl indol methanol, 3mmol of magnesium oxide, 0.06mmol of scandium trifluoromethanesulfonate, 0.9mmol of trimethylsilyl cyanide and 3mL of anhydrous chlorobenzene, stirring at 120 ℃ for 8 hours (tracking the reaction by thin-plate chromatography till the reaction is complete), cooling to room temperature after the reaction is finished, filtering to remove insoluble substances, rotationally concentrating the filtrate to remove the solvent, and performing gradient elution by using a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 25: 1-10: 1 as an eluent to obtain 1g (96.3mg, white solid, yield 99%) of a target product.
1H NMR(400MHz,CDCl3)δ8.90(s,1H),7.35(d,J＝7.0Hz,1H),7.30–7.21(m,3H),7.14–7.11(m,1H),6.80–6.77(m,2H),3.84(s,3H),2.22(s,3H)；13C NMR(101MHz,CDCl3)δ159.5,153.2(dd,J＝297.1,292.2Hz),137.9,137.6(d,J＝1.7Hz),130.8,130.6,128.6,125.9,121.9(d,J＝2.6Hz),119.4(d,J＝1.4Hz),113.9,113.4,103.9,93.7,87.1(dd,J＝27.1,18.4Hz),55.5,19.7；19F NMR(376MHz,CDCl3)δ-83.76(d,J＝22.6Hz),-84.07(d,J＝22.8Hz)；HRMS(ESI)calcd for C19H14F2N2NaO[M+Na]+:347.0966；found:347.0954。
Example 8
The reaction equation is:
taking a 25mL round-bottom flask, sequentially adding trifluoromethyl indolylmethanol for 2h (111.4mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL), stirring at 120 ℃ for 15 h (thin-plate chromatography tracking reaction till the reaction is complete), cooling to room temperature after the reaction is finished, filtering to remove insoluble substances, rotationally concentrating the filtrate to remove the solvent, and performing gradient elution by using a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 20: 1-10: 1 as an eluent to obtain a target product for 1h (100.5mg, white solid, yield 93%).
1H NMR(400MHz,CDCl3)δ8.80(s,1H),7.90–7.87(m,3H),7.64(d,J＝7.0Hz,1H),7.53–7.42(m,3H),7.16(d,J＝8.9Hz,1H),6.75–6.70(m,2H),3.79(s,3H)；13C NMR(101MHz,CDCl3)δ159.4,153.8(dd,J＝297.7,292.8Hz),137.9,133.8,131.7(d,J＝1.8Hz),129.6(dd,J＝3.3,2.7Hz),129.3,129.2,128.6,126.7,126.0,125.2,124.6,121.7(d,J＝2.7Hz),121.4(dd,J＝4.1,2.7Hz),119.1(d,J＝1.9Hz),114.0,113.4,103.8,93.6,86.3(dd,J＝26.8,19.5Hz),55.2；19F NMR(376MHz,CDCl3)δ-82.17(d,J＝20.8Hz),-82.68(d,J＝21.0Hz)；HRMS(ESI)calcd for C22H14F2N2NaO[M+Na]+:383.0966；found:383.0953。
Example 9
The reaction equation is:
taking a 25mL round-bottom flask, sequentially adding trifluoromethyl indolylmethanol 2i (98.2mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL), stirring at 120 ℃ for 24 hours (thin-plate chromatography tracking reaction till the reaction is complete), cooling to room temperature after the reaction is finished, filtering to remove insoluble substances, rotationally concentrating the filtrate to remove the solvent, and performing gradient elution by using a mixed solution of petroleum ether and ethyl acetate in a volume ratio of 20: 1-9: 1 as an eluent to obtain a target product 1i (62.6mg, a light yellow solid, and the yield of 66%).
1H NMR(600MHz,CDCl3)δ8.66(s,1H),7.32(d,J＝4.9Hz,1H),7.25(d,J＝8.9Hz,1H),6.99(t,J＝4.1Hz,1H),6.95(s,1H),6.85(d,J＝7.9Hz,1H),6.84(s,1H),3.87(s,3H)；13C NMR(151MHz,CDCl3)δ159.8,153.5(dd,J＝300.6,293.4Hz),137.9,134.5(d,J＝6.7Hz),127.2(t,J＝5.0Hz),127.1,126.0(dd,J＝5.7,2.8Hz),121.8,119.7(d,J＝1.8Hz),119.6(dd,J＝5.0,2.7Hz),113.7,104.7,93.8,83.5(dd,J＝24.9,23.4Hz),55.5；19F NMR(565MHz,CDCl3)δ-80.24(d,J＝17.9Hz),-83.87(d,J＝17.9Hz)；HRMS(ESI)calcd for C16H10F2N2NaOS[M+Na]+:339.0374；found:339.0363。
Example 10
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indolylmethanol 2j (119.2mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 8 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature after the reaction is finished, filtering is carried out to remove insoluble substances, filtrate is rotated and concentrated to remove a solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 25: 1-15: 1 as an eluent, so that the target product 1j (77.7mg, white solid, yield 67%) is obtained.
1H NMR(600MHz,CDCl3)δ7.62(t,J＝7.7Hz,1H),7.56–7.52(m,3H),7.40–7.31(m,5H),7.12(d,J＝8.9Hz,1H),6.81(dd,J＝8.9,2.2Hz,1H),6.73(d,J＝2.1Hz,1H),3.77(s,3H)；13C NMR(151MHz,CDCl3)δ159.9,154.0(dd,J＝298.1,294.0Hz),139.1,136.0,132.6(dd,J＝4.5,3.2Hz),130.0,128.9(t,J＝3.6Hz),128.6,127.9,126.6,122.2,121.4(dd,J＝4.6,2.9Hz),119.9(d,J＝2.5Hz),113.6,112.7,109.1,93.2,87.6(dd,J＝22.0,20.1Hz),55.6；19F NMR(565MHz,CDCl3)δ-81.41(d,J＝22.2Hz),-85.25(d,J＝22.2Hz)；HRMS(ESI)calcd for C24H17F2N2O[M+H]+:387.1303；found:387.1296。
Example 11
The reaction equation is:
a25 mL round-bottom flask is taken, trifluoromethyl indolylmethanol 2k (123.4mg,0.3mmol), magnesium oxide (3mmol), scandium trifluoromethanesulfonate (0.06mmol), trimethylsilyl cyanide (0.9mmol) and anhydrous chlorobenzene (3mL) are sequentially added, stirring is carried out at 120 ℃ for 15 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling to room temperature after the reaction is finished, filtering is carried out to remove insoluble substances, filtrate is rotated and concentrated to remove a solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 25: 1-15: 1 as an eluent, so that the target product 1k (94.9mg, white solid and yield 79%) is obtained.
1H NMR(400MHz,CDCl3)δ7.38–7.29(m,8H),7.20(d,J＝6.8Hz,2H),7.08(d,J＝8.9Hz,1H),6.76(dd,J＝8.9,2.2Hz,1H),6.68(d,J＝2.1Hz,2H),5.45(s,2H),3.78(s,3H)；13C NMR(151MHz,CDCl3)δ159.6,153.9(dd,J＝297.7,293.7Hz),138.6,135.7,132.7(dd,J＝4.4,3.4Hz),129.0,128.8(t,J＝3.6Hz),128.5,128.1,127.8,126.7,122.4,120.1(d,J＝2.5Hz),119.9(dd,J＝4.5,3.1Hz),113.0,112.9,108.9,92.9,87.7(dd,J＝22.0,20.1Hz),55.5,49.1；19F NMR(376MHz,CDCl3)δ-81.75(d,J＝23.1Hz),-85.69(d,J＝23.0Hz)；HRMS(ESI)calcd for C25H19F2N2O[M+H]+:401.1460；found:401.1451。
Example 12
The reaction equation is:
taking a 25mL round-bottom flask, sequentially adding 2l (108.4mg,0.3mmol) of trifluoromethyl indolylmethanol, 3mmol of magnesium oxide, 0.06mmol of scandium trifluoromethanesulfonate, 0.9mmol of trimethylsilyl cyanide and 3mL of anhydrous chlorobenzene, stirring at 120 ℃ for 15 hours (tracking the reaction by thin-plate chromatography till the reaction is complete), cooling to room temperature after the reaction is finished, filtering to remove insoluble substances, rotationally concentrating the filtrate to remove the solvent, and performing gradient elution by taking a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 25: 1-15: 1 as an eluent to obtain 1l (86.2mg, white solid, yield of 82%) of a target product.
1H NMR(600MHz,CDCl3)δ7.38–7.29(m,5H),7.08(d,J＝8.9Hz,1H),6.76(dd,J＝8.9,2.2Hz,1H),6.68(d,J＝2.1Hz,2H),6.01(ddt,J＝17.0,10.3,5.1Hz,1H),5.29(dd,J＝10.3,0.6Hz,1H),5.10(dd,J＝17.1,0.5Hz,1H),4.87(dt,J＝5.0,1.5Hz,2H),3.86(s,3H)；13C NMR(151MHz,CDCl3)δ159.5,153.9(dd,J＝297.7,293.5Hz),138.4,132.8(dd,J＝4.4,3.3Hz),131.6,128.8(t,J＝3.5Hz),128.5,127.8,122.3,119.9(d,J＝2.7Hz),119.7(dd,J＝4.4,3.2Hz),118.0,113.0,112.7,108.6,92.6,87.7(dd,J＝21.8,20.2Hz),55.5,47.7；19F NMR(565MHz,CDCl3)δ-81.96(d,J＝23.3Hz),-85.82(d,J＝23.2Hz)；HRMS(ESI)calcd for C21H17F2N2O[M+H]+:351.1303；found:351.1290。
Example 13
In order to verify the practicability of the invention, gram-scale amplification experiments are also carried out, and the effect is good. Moreover, when the starting trifluoromethyl indole carbinol 2a is scaled up to the 4mmol scale, the reaction still gives the desired product in the desired yield, fully demonstrating the utility of the present invention.
The reaction equation is:
a100 mL round-bottom flask is taken, trifluoromethyl indolylmethanol 2a (1.165g,4mmol), magnesium oxide (40mmol), scandium trifluoromethanesulfonate (0.8mmol), trimethylsilyl cyanide (12mmol) and anhydrous chlorobenzene (40mL) are sequentially added, stirring is carried out at 120 ℃ for 12 hours (thin-plate chromatography tracking reaction is carried out until the reaction is complete), cooling is carried out to room temperature after the reaction is finished, insoluble substances are removed by filtration, the filtrate is rotated and concentrated to remove the solvent, and gradient elution is carried out by taking a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 25: 1-10: 1 as an eluent, so that the target product 1a is obtained (695mg, the yield is 62%).
Example 14
The 2-cyanoindole-substituted gem-difluoroolefin compounds prepared in examples 1-13 simultaneously have indole, vinylidene fluoride and cyano groups, can be synthesized into other compounds through functional group transformation reaction, and are important organic synthesis intermediates.
Taking the 2-cyanoindole-substituted gem-difluoroolefin compound 1a prepared in example 13 as an example, the 2-cyanoindole-substituted gem-difluoroolefin compound 1a can be subjected to addition reaction with p-methylphenylthiophenol under the catalysis of tetramethylguanidine to synthesize thioether, and the reaction formula is as follows:
a10 mL round bottom flask was taken, and 2-cyanoindole-substituted gem-difluoroalkene compound 1a (0.2mmol), p-methylthiophenol (0.4mmol) and tetramethylguanidine (0.04mmol) were sequentially added, dichloroethane (1mL) was then added, the mixture was stirred at 80 ℃ for 12 hours, after the reaction was completed, the mixture was cooled to room temperature, the solvent was removed by rotary concentration, and gradient elution was performed using a mixed solution of petroleum ether and ethyl acetate at a volume ratio of 25:1 to 10:1 as an eluent, to obtain the objective compound 4(56.6mg, white solid, yield 70%).
1H NMR(600MHz,CDCl3)δ8.75(s,1H),7.83(d,J＝8.3Hz,1H),7.58(d,J＝7.6Hz,2H),7.44(d,J＝8.1Hz,2H),7.38–7.21(m,6H),7.16(d,J＝7.9Hz,1H),5.17(d,J＝16.3Hz,1H),2.35(s,3H)；13C NMR(151MHz,CDCl3)δ140.3,137.0,136.3,135.4,129.8,129.6(d,J＝284.2Hz),129.5,127.8,126.4,125.0,123.6,122.8,121.9(t,J＝2.8Hz),121.8,113.7,112.0,106.6,52.0(t,J＝24.8Hz),21.2；19F NMR(565MHz,CDCl3)δ-71.39(dd,J＝206.2,16.6Hz),-72.01(dd,J＝206.2,14.3Hz)；HRMS(ESI)calcd for C24H19F2N2S[M+H]+:405.1232；found:405.1237.
The 2-cyanoindole substituted gem-difluoroalkene compound 1a can also be reduced by sodium borohydride under the catalysis of cobalt dichloride to convert a cyano group into an amino compound, and the reaction formula is as follows:
taking a 10mL round-bottom flask, sequentially adding 2-cyanoindole-substituted gem-difluoroalkene compound 1a (0.2mmol), cobalt dichloride (0.4mmol) and di-tert-butyl dicarbonate (0.8mmol), then adding methanol (3mL), adding sodium borohydride in batches within ten minutes of ice bath, reacting at room temperature after the reaction is finished, rotationally concentrating to remove the solvent after the reaction is finished, and performing gradient elution by using a mixed solution of petroleum ether and ethyl acetate as an eluent in a volume ratio of 25: 1-10: 1 to obtain a target product 5(56.9mg, white solid and yield of 74%).
1H NMR(600MHz,CDCl3)δ9.22(s,1H),7.38–7.25(m,6H),7.18(d,J＝7.5Hz,2H),7.03(t,J＝7.5Hz,1H),4.89(s,1H),4.22(d,J＝6.3Hz,2H),1.48(s,3H)；13C NMR(151MHz,CDCl3)δ157.5,153.8(dd,J＝297.9,288.4Hz),135.6,134.4,128.6,128.4,127.3,127.1,122.4,119.9,119.6,111.2,105.5,88.4(dd,J＝20.7,17.3Hz),80.3,36.3,28.4,19F NMR(565MHz,CDCl3)δ-84.11(d,J＝31.1Hz),-88.52(dd,J＝31.1Hz)；HRMS(ESI)calcd for C22H23F2N2O2[M+H]+:385.1722；found:385.1717.
The 2-cyanoindole-substituted gem-difluoroolefin compound 1a can also react with a Grignard reagent to synthesize a 3-fluoro-beta-carboline compound, and the reaction formula is as follows:
taking a 25mL round-bottom flask, adding 2-cyano substituted geminal difluoroolefin (0.2mmol), adding anhydrous tetrahydrofuran (2mL) under nitrogen atmosphere, dropwise adding allyl magnesium bromide (1mmol/mL, 0.8mL) at 0 ℃, stirring at normal temperature for 15 hours after half an hour, adding saturated ammonium chloride aqueous solution (5mL) after the reaction is finished, quenching the reaction, extracting twice with ethyl acetate, combining organic phases, drying with anhydrous magnesium sulfate, filtering, and carrying out rotary concentration. The crude product was isolated and purified by column chromatography on silica gel (eluent petroleum ether: ethyl acetate 20/1-10/1, V/V) to give the desired product (36.9mg, white solid, 61% yield).
1H NMR(400MHz,CDCl3)δ8.31(s,1H),7.61–7.45(m,7H),7.40(d,J＝8.1Hz,1H),7.04–6.97(m,1H),6.22(ddt,J＝16.7,10.0,6.6Hz,1H),5.39(dd,J＝17.1,1.6Hz,1H),5.31(dd,J＝10.0,1.4Hz,1H),3.92(dt,J＝6.6,1.3Hz,2H)；13C NMR(101MHz,CDCl3)δ153.9(d,J＝225.9Hz),141.9,138.1(d,J＝15.5Hz),134.2,133.1(d,J＝2.0Hz),132.7(d,J＝3.3Hz),131.8(d,J＝4.7Hz),130.0,128.7,128.6,128.4,123.5,121.5(d,J＝5.7Hz),119.7,117.8,114.2(d,J＝35.5Hz),111.6,39.1；19F NMR(376MHz,CDCl3)δ-87.23(s)；HRMS calcd for C22H20FN2[M+H]+:331.1605；found:331.1599；1HRMS calcd for C20H16FN2[M+H]+:303.1292；found:303.1283。
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents and improvements made within the spirit and principle of the present invention are intended to be included therein.
Claims (9)
1. A2-cyanoindole-substituted gem-difluoroolefin compound is characterized in that the structural formula is shown as the formula (1):
wherein R is1、R2、R3Are each independently of the other R1One selected from hydrogen, halogen atom, hydroxyl, cyano, ester group, methyl, ethyl or methoxy; r2One selected from hydrogen, phenyl, halogen substituted phenyl, alkyl substituted phenyl, C1-C6 branched alkyl, benzyl or allyl; r3Is selected from one of phenyl, halogen substituted phenyl, alkyl substituted phenyl, naphthyl or thienyl.
2. A process for the preparation of a 2-cyanoindole-substituted gem-difluoroolefin compound according to claim 1, comprising the steps of: the 2-cyanoindole-substituted gem-difluoroolefin compound is prepared by taking trifluoromethyl indole methanol compound and trimethylsilyl cyanide as raw materials, and carrying out heating reaction in a solvent under the action of a Lewis acid catalyst and an inorganic base.
3. The method for preparing a 2-cyanoindole-substituted gem-difluoroolefin compound according to claim 2, wherein the trifluoromethyl indole carbinol compound is a compound represented by formula (2):
the mol ratio of the trifluoromethyl indole methanol compound to the trimethylsilyl cyanide is 1: 2-3; wherein R is1、R2、R3Are each independently of the other R1One selected from hydrogen, halogen atom, hydroxyl, cyano, ester group, methyl, ethyl or methoxy; r2One selected from hydrogen, phenyl, halogen substituted phenyl, alkyl substituted phenyl, C1-C6 branched alkyl, benzyl or allyl; r3Is selected from one of phenyl, halogen substituted phenyl, alkyl substituted phenyl, naphthyl or thienyl.
4. The method for preparing a 2-cyanoindole-substituted gem-difluoroalkene compound according to claim 2, wherein the Lewis acid catalyst is scandium trifluoromethanesulfonate, and the molar ratio of the trifluoromethyl indole carbinol compound to the scandium trifluoromethanesulfonate is 1: 0.05-1: 0.2.
5. The method for preparing a 2-cyanoindole-substituted gem-difluoroolefin compound according to claim 2, wherein the inorganic base is any one of calcium oxide, magnesium oxide, barium oxide, zinc oxide and aluminum oxide, and the molar ratio of the inorganic base to the trifluoromethyl indole carbinol compound is 10: 1.
6. The method for preparing a 2-cyanoindole-substituted gem-difluoroolefin compound according to claim 2, wherein the solvent is any one of chlorobenzene, toluene, acetonitrile or dichloroethane, and the concentration of the trifluoromethyl indole carbinol compound in the solvent is 0.05-0.5 mol/L;
the heating reaction temperature is 80-140 ℃, and the heating reaction time is 6-24 h.
7. Use of a 2-cyanoindole-substituted geminal difluoroalkene compound according to claim 1 as an intermediate in organic synthesis.
8. The use of claim 7, wherein the 2-cyanoindole-substituted geminal difluoroalkene compound and the methylthiophenol are subjected to an addition reaction under the catalysis of tetramethylguanidine to synthesize the thioether compound.
9. The use of claim 7, wherein the 2-cyanoindole-substituted gem-difluoroalkene compound and the methylphenylthiol are subjected to substitution reaction under the catalysis of cobalt dichloride to synthesize the amino compound.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111012397.2A CN113527177A (en) | 2021-08-31 | 2021-08-31 | 2-cyanoindole-substituted gem-difluoroolefin compound and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111012397.2A CN113527177A (en) | 2021-08-31 | 2021-08-31 | 2-cyanoindole-substituted gem-difluoroolefin compound and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113527177A true CN113527177A (en) | 2021-10-22 |
Family
ID=78122941
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111012397.2A Pending CN113527177A (en) | 2021-08-31 | 2021-08-31 | 2-cyanoindole-substituted gem-difluoroolefin compound and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113527177A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114702399A (en) * | 2022-05-05 | 2022-07-05 | 信阳师范学院 | 2-trifluoroalkyl-1, 4-naphthoquinone compound and synthetic method thereof |
| CN114804998A (en) * | 2022-04-29 | 2022-07-29 | 上海毕得医药科技股份有限公司 | Preparation method of 3-substituted 2-fluoro-1, 5-diene compound |
| CN114957085A (en) * | 2022-05-19 | 2022-08-30 | 华南师范大学 | Synthetic method and application of polycyano-substituted indole heterocyclic compound |
| CN115010714A (en) * | 2022-07-05 | 2022-09-06 | 河北医科大学 | Azepine [4,5-b ] indole alkaloid skeleton compound and preparation method thereof |
| CN115448865A (en) * | 2022-09-23 | 2022-12-09 | 武汉大学 | Method for asymmetrically synthesizing sertraline intermediate |
| CN115448816A (en) * | 2022-09-16 | 2022-12-09 | 中国石油大学(华东) | Synthesis method of beta fluoro-alkenyl alcohol |
| CN115490627A (en) * | 2022-09-23 | 2022-12-20 | 武汉大学 | Method for synthesizing chiral 4-gem-difluoroalkenyl substituted pyrrolidone |
| CN115850111A (en) * | 2023-01-03 | 2023-03-28 | 天津师范大学 | Preparation method of nickel-catalyzed aliphatic amine containing gem-difluoroolefin structure |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040248872A1 (en) * | 2001-09-28 | 2004-12-09 | Tetsuya Abe | Difluoroalkene derivative, pest control agent containing the same, and intermediate therefor |
| US20090312288A1 (en) * | 2008-04-16 | 2009-12-17 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| CN102219638A (en) * | 2010-04-16 | 2011-10-19 | 中国科学院上海有机化学研究所 | Fluorination method of vinyl carboxylic acid |
| CN102781893A (en) * | 2010-03-03 | 2012-11-14 | 大金工业株式会社 | Method for producing substituted fluorine-containing olefin |
| JP2016145277A (en) * | 2015-02-06 | 2016-08-12 | ニチアス株式会社 | Crosslinking agent |
| CN111155141A (en) * | 2020-01-20 | 2020-05-15 | 中国科学技术大学 | Method for electrochemically synthesizing gem-difluoroolefin |
| CN112724171A (en) * | 2021-01-06 | 2021-04-30 | 南京林业大学 | 2-phosphonyl-3-fluorovinyl indole compound and preparation method thereof |
-
2021
- 2021-08-31 CN CN202111012397.2A patent/CN113527177A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040248872A1 (en) * | 2001-09-28 | 2004-12-09 | Tetsuya Abe | Difluoroalkene derivative, pest control agent containing the same, and intermediate therefor |
| US20090312288A1 (en) * | 2008-04-16 | 2009-12-17 | Takeda Pharmaceutical Company Limited | Kinase inhibitors |
| CN102781893A (en) * | 2010-03-03 | 2012-11-14 | 大金工业株式会社 | Method for producing substituted fluorine-containing olefin |
| CN102219638A (en) * | 2010-04-16 | 2011-10-19 | 中国科学院上海有机化学研究所 | Fluorination method of vinyl carboxylic acid |
| JP2016145277A (en) * | 2015-02-06 | 2016-08-12 | ニチアス株式会社 | Crosslinking agent |
| CN111155141A (en) * | 2020-01-20 | 2020-05-15 | 中国科学技术大学 | Method for electrochemically synthesizing gem-difluoroolefin |
| CN112724171A (en) * | 2021-01-06 | 2021-04-30 | 南京林业大学 | 2-phosphonyl-3-fluorovinyl indole compound and preparation method thereof |
Non-Patent Citations (4)
| Title |
|---|
| MIAOLIN KE等: "Copper-Catalyzed 1,6-Hydrodifluoroacetylation of para-Quinone Methides at Ambient Temperature with Bis(pinacolato)diboron as Reductant", 《ADVANCED SYNTHESIS & CATALYSIS》 * |
| ZHEN YANG等: "Synthesis of gem-Difluoro Olefins through C-H Functionalization and β-fluoride Elimination Reactions", 《ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》 * |
| 李峰: "一锅多步转化选择性构建有机氟化物", 《天津大学博士学位论文》 * |
| 蓝云: "镍催化烯烃的还原氨甲酰基烷基化和α-三氟甲基烯烃的还原烷基化反应的研究", 《中国科学技术大学博士学位论文》 * |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114804998B (en) * | 2022-04-29 | 2023-10-10 | 上海毕得医药科技股份有限公司 | Preparation method of 3-substituted 2-fluoro-1, 5-diene compound |
| CN114804998A (en) * | 2022-04-29 | 2022-07-29 | 上海毕得医药科技股份有限公司 | Preparation method of 3-substituted 2-fluoro-1, 5-diene compound |
| CN114702399A (en) * | 2022-05-05 | 2022-07-05 | 信阳师范学院 | 2-trifluoroalkyl-1, 4-naphthoquinone compound and synthetic method thereof |
| CN114957085A (en) * | 2022-05-19 | 2022-08-30 | 华南师范大学 | Synthetic method and application of polycyano-substituted indole heterocyclic compound |
| CN114957085B (en) * | 2022-05-19 | 2023-11-14 | 华南师范大学 | Synthetic method and application of polycyano substituted indole heterocyclic compound |
| CN115010714A (en) * | 2022-07-05 | 2022-09-06 | 河北医科大学 | Azepine [4,5-b ] indole alkaloid skeleton compound and preparation method thereof |
| CN115010714B (en) * | 2022-07-05 | 2023-06-02 | 河北医科大学 | Azepino [4,5-b ] indole alkaloid skeleton compound and preparation method thereof |
| CN115448816A (en) * | 2022-09-16 | 2022-12-09 | 中国石油大学(华东) | Synthesis method of beta fluoro-alkenyl alcohol |
| CN115448816B (en) * | 2022-09-16 | 2024-04-12 | 中国石油大学(华东) | Synthesis method of beta-fluoro alkenyl alcohol |
| CN115490627A (en) * | 2022-09-23 | 2022-12-20 | 武汉大学 | Method for synthesizing chiral 4-gem-difluoroalkenyl substituted pyrrolidone |
| CN115448865A (en) * | 2022-09-23 | 2022-12-09 | 武汉大学 | Method for asymmetrically synthesizing sertraline intermediate |
| CN115448865B (en) * | 2022-09-23 | 2023-11-17 | 武汉大学 | Asymmetric synthesis method of cetracetam intermediate |
| CN115850111A (en) * | 2023-01-03 | 2023-03-28 | 天津师范大学 | Preparation method of nickel-catalyzed aliphatic amine containing gem-difluoroolefin structure |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113527177A (en) | 2-cyanoindole-substituted gem-difluoroolefin compound and preparation method and application thereof | |
| CN114634482B (en) | Diazonium difluoro methylation reagent and synthetic method and application thereof | |
| CN116063223A (en) | 10-perfluoroalkyl-5, 10-indano [1,2-b ] indole compound and synthesis method thereof | |
| CN109651333B (en) | 2-indol-3-yl-quinoline compound with anti-tumor activity and preparation method and application thereof | |
| Ram et al. | A facile access to the synthesis of functionalised unsymmetrical biaryls from 2 H-pyran-2-ones through carbanion induced C–C bond formation | |
| CN110272403B (en) | Method for synthesizing carbamate containing dihydrobenzofuran ring and trifluoromethyl | |
| CN105272987B (en) | A kind of preparation method of 3 cyano group N dislocation porphyrin compound | |
| CN113307804A (en) | Synthetic method and application of fluorine-containing indole quinoline compound | |
| CN109293550B (en) | Trifluoromethyl-containing 3, 6' -asymmetric bis-indole compound and synthesis method thereof | |
| CN111517954A (en) | (Z) -5-fluoro-2-difluoromethylene olefin derivative and preparation method thereof | |
| CN113461589B (en) | Chiral 2, 3-disubstituted indoleamine compound and preparation method thereof | |
| CN110194760B (en) | Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones | |
| CN111205255B (en) | CMe-containing material 2 CF 3 Synthesis method of flavonoid compound of group | |
| CN111187184B (en) | Novel method for synthesizing sulfonyl ketoamide | |
| CN108503578B (en) | Synthetic method of indeno- [1,2-b ] indole-10 (5H) -ketone compound | |
| CN113072524B (en) | Polyfluoroaryl substituted alkane and preparation method thereof | |
| CN115490728B (en) | Synthesis method of allyl phosphine derivative | |
| CN114213412B (en) | Method for synthesizing pyrazoloquinoline compound from 2-pyrazoloaniline derivative and ether under acid catalysis | |
| CN110590717B (en) | Polysubstituted ketene imine and synthetic method thereof | |
| CN108147989A (en) | A kind of beta-amido ketone derivatives and its synthetic method | |
| CN110386929B (en) | Copper catalyst-mediated heterocycle-heterocycle C-N cross dehydrogenation coupling reaction method | |
| CN111285846B (en) | 2- (2-indolyl) -acetate derivative and synthesis method thereof | |
| CN115215783B (en) | Propargyl substituted chiral 3-amino-3, 3-disubstituted oxindole compound, and synthetic method and application thereof | |
| CN111333526B (en) | Preparation method of N-aryl glycine ester derivative | |
| CN113024475B (en) | Synthetic method of quinoxalinone compound |
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 |