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Preparation method of alpha-alkenyl-alpha, alpha-difluoroaryl ketone compound and product

A technology for difluoroaryl ketones and compounds is applied in the field of organic compounds, can solve problems such as undeveloped ones, and achieve the effects of cheap catalyst, high economic benefit and simple post-processing

Active Publication Date: 2022-05-17
NANJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although the reaction of non-fluorinated enolsilyl ethers with alkynes has been reported, no direct addition of difluoroenolsilyl ethers to aryl alkynes to obtain α-alkenyl-α,α-difluoro Keto method

Method used

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  • Preparation method of alpha-alkenyl-alpha, alpha-difluoroaryl ketone compound and product
  • Preparation method of alpha-alkenyl-alpha, alpha-difluoroaryl ketone compound and product
  • Preparation method of alpha-alkenyl-alpha, alpha-difluoroaryl ketone compound and product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] (1) Place a 20mL Schlenk tube equipped with a magnetic stirrer in an oven to dry for one hour, and add 0.2 g of Molecular sieves are then dried in an oven for half an hour, and after taking them out, they are hot and plugged with a rubber stopper and a nitrogen balloon. After cooling, ultra-dry 1,2-dichloroethane solvent (2 mL) was added thereto, followed by sealing the tube for nitrogen three times, and then adding 1-ethynyl-4-methoxybenzene (66.1 mg, 0.5mmol, 1equiv.), ((2,2-difluoro-1-phenylvinyl)oxy)trimethylsilane (172.2mg, 0.75mmol, 1.5equiv.), and ferric chloride ( 16.2mg, 0.1mmol, 0.2equiv.) and trimethylchlorosilane (108.7mg, 1mmol, 2equiv.). The mixture was stirred at -78°C for 12 hours.

[0045] (2) Remove the solvent by rotary evaporation subsequently, and the crude product is purified by silica gel column chromatography (column chromatography separation condition: the stationary phase is 300~400 mesh silica gel powder, and the mobile phase is ethyl aceta...

Embodiment 2

[0050] Example 2 is basically the same as Example 1, except that in step (1), the catalysts are different, as shown in Table 1 below.

[0051] Table 1

[0052] catalyst Yield(%) MgBr 2 (1 equiv.)

<10

AlCl 3 (1 equiv.)

<10

TiBr 4 (1 equiv.)

<10

CuBr 2 (1 equiv.)

<10

GaBr 3 (1 equiv.)

<10

InCl 3 (1 equiv.)

16 SnCl 4 (1 equiv.)

32 BiBr 3 (1 equiv.)

<10

FeCl 3 (1 equiv.)

57 FeBr 3 (1 equiv.)

34 FeBr 2 (1 equiv.)

<10

Fe(OTf) 3 (1 equiv.)

18 FeCl 3 (0.2 equiv.)

39 FeCl 3 (0.2equiv.), TMSCl (2equiv.)

79 TMSCl (2 equiv.) <5

[0053] As can be seen from Table 1, under the same reaction conditions, the use of catalysts, such as: magnesium bromide, aluminum trichloride, titanium tetrabromide, copper bromide, gallium bromide, indium trichloride, tin tetrachloride, Synthesis of 2,2-difluoro-3-(4-methoxyphenyl)-1-ph...

Embodiment 3

[0056] Example 3 is basically the same as Example 1, except that in step (1), the solvent and temperature are different, as shown in Table 2 below.

[0057] Table 2

[0058] solvent temperature(℃) Yield(%) Tetrahydrofuran -78℃ 0 1,4-dioxane -78℃ 0 N,N-Dimethylformamide -78℃ 0 Acetonitrile -78℃ 0 N,N-Dimethylacetamide -78℃ 0 n-Hexane -78℃ 0 Toluene -78℃ 0 Dichloromethane -78℃ 40 1,2-Dichloroethane -78℃ 79 1,2-Dichloroethane -40℃ 46 1,2-Dichloroethane 0℃ 41 1,2-Dichloroethane 60℃ 12

[0059] It can be seen from Table 3 that at -78°C, solvents containing heteroatoms, such as tetrahydrofuran, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, 1, Synthesis of 2,2-difluoro-3-(4-methoxyphenyl)-1-phenyl-3-en-1-one from 4-dioxane with very small yield; at -78°C , use a non-coordinating solvent, such as: toluene or n-hexane to synthesize the target product, with a very small y...

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PUM

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Abstract

The invention discloses a preparation method of an alpha-alkenyl-alpha, alpha-difluoroaryl ketone compound and a product, and the preparation method comprises the following step: carrying out direct cross-coupling reaction on an aryl alkyne compound and difluoroenol silyl ether in a solvent under the action of a catalyst to obtain the alpha-alkenyl-alpha, alpha-difluoroaryl ketone compound. The difluoroenol silyl ether is used as a coupling substrate, so that the reaction has mild conditions and operation convenience, and the preparation method has the characteristics of simple post-treatment, cheap and small-amount catalyst, high economic benefit and the like.

Description

technical field [0001] The invention belongs to the technical field of organic compounds, and in particular relates to a preparation method and products of α-alkenyl-α, α-difluoroaryl ketone compounds. Background technique [0002] In recent years, studies have shown that incorporation of difluoroalkyl groups into organic molecules can endow the parent molecule with significantly enhanced lipophilicity, metabolic stability, and bioavailability, making it potentially useful in pharmaceuticals, agrochemicals, and materials science . In addition to common difluoroalkyl-containing compounds (e.g., halodifluoromethyl compounds, α,α-difluoroketones) that have been widely used as difluoroalkylating agents, it has recently been shown that difluoroenol silyl ethers can also Used as a general reagent, it can efficiently perform various organic transformations while introducing difluoroalkyl groups into organic molecules. [0003] On the other hand, the incorporation of non-fluorinat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C45/00C07C45/51C07C49/84B01J27/128B01J31/02B01J31/30
CPCC07C45/00C07C45/511C07C49/84B01J27/128B01J31/0275B01J31/30B01J2231/4272
Inventor 沈志良褚雪强郭檬檬
Owner NANJING UNIV OF TECH
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