Beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound and synthesis method and application thereof

A technology of fluoroalkyl ketones and synthetic methods, which is applied in the fields of carbon-based compound preparation, organic chemical methods, chemical instruments and methods, etc.

Inactive Publication Date: 2019-10-25
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] So far, there have been many reports on the addition of fluorinated nucleophiles to highly active electrophiles, but due to the inertness of alkenes,

Method used

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  • Beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound and synthesis method and application thereof
  • Beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound and synthesis method and application thereof
  • Beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound and synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Synthesis of β-all-carbon quaternary carbon-α-fluoroalkyl ketone Ⅲ-1:

[0086]

[0087] Add 3.6 mg perchloric acid (70% wt), distilled water (2.5 mL), olefin I-1 (33.1 mg, 0.25 mmol), and phenyl-substituted difluoroenol silyl ether II-1 to a 5.0 mL reaction flask in sequence (570mg, 2.5mmol), the reaction solution was stirred at 50°C for 15h. TLC detects that the raw materials have basically reacted, and the reaction is stopped. The reaction solution was extracted with ethyl acetate for 3 times, dried over anhydrous sodium sulfate, transferred to a 50mL round bottom flask, added about 1.0g of crude silica gel, spin-dried, followed by column chromatography and eluent (petroleum ether), to obtain product III- 1 is 66.3mg of colorless liquid, the yield is 92%. 1 H NMR (400MHz, CDCl 3 ):δ7.56-7.54(m,2H),7.45-7.41(m,1H),7.36-7.34(m,2H),7.26-7.17(m,5H),2.46-2.37(m,1H),1.99 -1.90(m,1H),1.60(s,3H),0.75(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl 3 ): δ191.28(t, J=30.3Hz), 13...

Embodiment 2

[0089] Synthesis of β-all-carbon quaternary carbon-α-fluoroalkyl ketone Ⅲ-2:

[0090]

[0091] Add trifluoromethanesulfonic acid (3.8mg, 0.025mmol), olefin I-2 (37.6mg, 0.25mmol), phenyl-substituted difluoroenolsilyl ether II-1 (85.5, 0.375 mmol), tetrahydrofuran (2.5 mL); the reaction solution was stirred at room temperature for 5 h. TLC detects that the raw material has basically reacted completely, and the reaction is stopped. The reaction solution was transferred to a 50mL round-bottomed flask, and the solvent was drained under the oil pump, followed by direct column chromatography and eluent (DCM / petroleum ether=1 / 20) to obtain 63.6 mg of product III-2 as a colorless liquid, Yield 83%. 1 H NMR (400MHz, CDCl 3 ):δ7.64-7.62(m,2H),7.49-7.46(m,1H),7.33-7.26(m,4H),6.93-6.89(m,2H),2.40-2.31(m,1H),1.98 -1.89(m,1H),1.58(s,3H),0.73(t,J=1.9Hz,3H); 13 C NMR (100MHz, CDCl 3 ): δ190.93(t, J=30.2Hz), 161.88(d, J=245.3Hz), 134.22(t, J=1.9Hz), 133.98(dd, J=4.8, 4.5Hz), 133.40, 1...

Embodiment 3

[0093] Synthesis of β-all-carbon quaternary carbon-α-fluoroalkyl ketone Ⅲ-3:

[0094]

[0095] In the 5.0mL reaction flask, add H 2 SO 4 (5mg, 0.05mmol), olefin I-3 (41.7mg, 0.25mmol), phenyl-substituted difluoroenol silyl ether II-1 (285.4mg, 1.25mmol), toluene (2.5mL); After stirring at 30°C for 20h. TLC detects that the raw material has basically reacted completely, and the reaction is stopped. Transfer the reaction solution to a 50mL round-bottomed flask, drain the solvent under the oil pump, perform direct column chromatography, eluent (dichloromethane / petroleum ether=1 / 20), and obtain product III-3 as a colorless liquid 68.4 mg, yield 85%. 1 H NMR (400MHz, CDCl 3 ):δ7.67-7.65(m,2H),7.49-7.46(m,1H),7.31-7.24(m,4H),7.20-7.18(m,2H),2.38-2.29(m,1H),1.97 -1.88(m,1H),1.56(s,3H),0.72(t,J=7.6Hz,3H); 13 C NMR (100MHz, CDCl 3 ): δ190.60(t, J=30.3Hz), 136.91(t, J=2.4Hz), 134.11(t, J=2.1Hz), 133.46, 133.22, 130.18, 129.77(t, J=4.1Hz), 128.16, 128.11, 120.58(t, J=260.2Hz)...

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Abstract

The invention discloses a beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound and a synthesis method and application thereof. The compound has the structure shown in the following equation, has potential biological activity and pharmacodynamic activity, provides a strong technical support for development of new drugs, and has high practical value; and the synthesis method starts from olefin and the nucleophile agent fluoroenol silane, and efficiently synthesizes the beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound in one step through a simple addition reaction. The beta-all carbon quaternary carbon-alpha-fluoroalkyl ketone compound and the synthesis method and application thereof have the characteristics that raw materials are cheap and readily available;the reaction condition is mild and operation is simple; and the application range of substrates is wide, and the higher yield can be obtained.

Description

technical field [0001] The invention belongs to the technical field of organic compounds, and relates to β-all-carbon quaternary carbon-α-fluoroalkyl ketone compounds and a method for synthesizing the compounds starting from fluoroenol silicon ethers and simple olefins. Background technique [0002] Fluorine is located in the main group VII of the second period of the periodic table, and is the most electronegative element with a small atomic radius. Many research results have shown that the introduction of fluorine atoms or fluorine-containing groups into organic compounds can improve the physical and chemical properties of the corresponding compounds, as well as increase the bioavailability, lipophilicity, binding affinity, and metabolic stability of bioactive molecules. properties and membrane permeability. Therefore, the selective introduction of fluorine atoms or fluorine-containing groups into known drugs or bioactive molecules is an important means for drug modificat...

Claims

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Application Information

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IPC IPC(8): C07C45/00C07C49/813C07C67/00C07C69/712C07C49/84C07D333/22C07C49/733C07H15/203C07H1/00
CPCC07C45/00C07C49/813C07C67/00C07C69/712C07C49/84C07D333/22C07C49/733C07H15/203C07H1/00C07B2200/07C07C2601/14C07C2602/08C07C2602/10C07C2602/12
Inventor 周剑胡小思余金生
Owner EAST CHINA NORMAL UNIV
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