Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Difluoromethylation reaction of paracarbonyl copound participated with [(phenylsulfonyl) difluoromethyl] trimethyl silane

A technology of carbonyl compounds and trimethylsilane, which is applied in the field of high-efficiency difluoromethylation reagent-[difluoromethyl]trimethylsilane, which can solve the problems of reduced utilization, excessive carbonyl substrates, non-compliance with environmental protection, etc. problems, to achieve the effect of easy condition control and high yield

Inactive Publication Date: 2007-01-17
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method can carry out nucleophilic addition reaction to many carbonyl compounds, and then reduce the sulfone group to obtain difluoromethyl alcohol, there are the following disadvantages: (a) the reaction conditions are harsh (need to strictly control the low temperature -78 ° C); ( b) excess carbonyl substrate is required; (c) excess base is required, which makes substrates (especially aliphatic aldehydes) susceptible to enolization and thus reduces utilization; (d) the removal of sulfone groups involves environmental unfriendliness The reagent (sodium amalgam) does not meet the requirements of environmental protection

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Difluoromethylation reaction of paracarbonyl copound participated with [(phenylsulfonyl) difluoromethyl] trimethyl silane
  • Difluoromethylation reaction of paracarbonyl copound participated with [(phenylsulfonyl) difluoromethyl] trimethyl silane
  • Difluoromethylation reaction of paracarbonyl copound participated with [(phenylsulfonyl) difluoromethyl] trimethyl silane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] [(Benzenesulfonyl)difluoromethyl]trimethylsilane (TMS-CF 2 SO 2 A typical preparation method of Ph): Cool a solution of tetrahydrofuran (50mL) containing difluorobromomethylphenyl sulfone (5.0g, 18.4mmol) and trimethylchlorosilane (3.8mL, 27.7mmol) to -78°C, then A solution of n-butyllithium in hexane (1.6M, 20.7 mL, 33.2 mmol) was added slowly. The reaction mixture was stirred at -78°C for 1 hour, then quenched by the addition of cold saturated aqueous ammonium chloride. The mixed solution was extracted three times with diethyl ether (50 mL each time), and then the combined organic phases were washed with cold saturated aqueous sodium chloride solution and water respectively, and dried over anhydrous sodium sulfate. After removing the solvent on a rotary evaporator, the crude product was distilled under reduced pressure to obtain 3.8 g of [(benzenesulfonyl)difluoromethyl]trimethylsilane, yield: 78%. Boiling point 102-104 ℃ 1 mm Hg. NMR Characterization: 1 H NMR (C...

Embodiment 2

[0018] Carbonyl compound (2) and TMSCF 2 SO 2 Typical method of Ph reaction: under nitrogen protection, 2-naphthaldehyde (2a, 78mg, 0.5mmol) and TMSCF 2 SO 2 Ph (1, 0.6 mmol) was dissolved in dry THF (2.5 mL) and cooled to -78°C. Then, 13 mg of tetrabutyl(triphenyldifluoro)ammonium silicate (TBAF) was added to the above mixed solution. The reaction system was slowly warmed to room temperature with stirring, and stirred overnight. Then tetrabutylammonium fluoride (TBAF, 1.0 mol / L, 0.65 mL) was added into the reaction mixture, stirred for 30 minutes, and then 5 mL of saline solution was added. Extract with diethyl ether 3 times, 15 ml each time. The combined organic phases were dried over anhydrous magnesium sulfate, and the solvent was removed under vacuum, and the crude product was separated by silica gel column chromatography to obtain product 3a, 141 mg of white solid, with a yield of 81%. NMR data: 1 H NMR (CDCl 3 ): δ3.67(s, 1H); 5.77(d, J=12Hz, 1H); 7.35-8.15(m, 1...

Embodiment 3

[0020] Typical method of desulfone reaction involving magnesium metal: in a solution containing compound 3a (250mg, 0.7mmol) and 7.5 milliliters of dimethylformamide (DMF), add 4 milliliters of 1:1 acetic acid-sodium acetate buffered aqueous solution (8mol / L). 252 mg of magnesium bars were added in portions to the reaction solution, and then the mixture was stirred at room temperature for 3 hours. Then 30 ml of water was added, and extracted three times with 20 ml of ether. The combined organic phases were washed with saturated aqueous sodium bicarbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. After removing the solvent in a rotary evaporator, the crude product was separated by silica gel column chromatography to obtain product 4a as a white solid, 133 mg, yield 91%. NMR data: 1 H NMR (CDCl 3 ): δ2.93(s, 1H); 5.86(td, J=56.2Hz, 4.7Hz, 1H); 4.95(td, J=10.1Hz, 4.7Hz, 1H); 7.45-7.60(m, 3H); 7.80-7.92(m, 4H). 13 C NMR (CDCl 3): δ73.74(t, J=...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
boiling pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a process for synthesizing difluoro methanol product yield including difluoro methanol from difluoro-methylation reaction of ((phenylsulfonyl) difluoromethyl) trimethyl silicane adding carbonyl compound (aldehyde or ketone), the process consists of fluorinion-initiated (phenylsulfonyl) difluoromethyl methylation reaction and magnesium-participated reduction de-sulfonation reaction, The advantages of the disclosed process include simple process, high yield, economy and reaction environment friendliness.

Description

technical field [0001] The invention relates to a high-efficiency difluoromethylation reagent-[(benzenesulfonyl)difluoromethyl]trimethylsilane (TMSCF 2 SO 2 Ph), used this reagent for the first time to achieve the difluoromethylation reaction of catalytic carbonyl compounds under the trigger of fluoride ion. TMSCF 2 SO 2 Ph reagent is an important difluoromethylation reagent for the synthesis of fluorine-containing drugs and fluorine-containing materials. The method of the invention is a difluoromethylation reaction initiated by fluoride ions and a selective desulfone reaction participated in by metal magnesium, and is an environment-friendly reaction. Background technique [0002] Fluorochemicals are widely used in drug design and new material development. The selective introduction of fluorine atoms or fluorine-containing building blocks into organic molecules can greatly enhance the biological activity of these molecules. Therefore, the research on selective fluorin...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07C29/38C07C29/62
Inventor 胡金波倪传法
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products