Method for preparing 6-difluoro alkyl ketone

A technology of difluoroalkyl ketone and monobromodifluoroacetate, which is applied in the field of preparation of 6-difluoroalkyl ketone, can solve problems such as difficulties, and achieve improved synthesis efficiency, good reaction yield, and good application value Effect

Active Publication Date: 2017-05-31
ZHEJIANG NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

[0007] Correspondingly, the long-distance aryl difluoroalkylation reaction of alkenes has not been reported. The main reason is how to selectively achieve arylation at a suitable position at the far end while difluoroalkylation , still face difficulties

Method used

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  • Method for preparing 6-difluoro alkyl ketone
  • Method for preparing 6-difluoro alkyl ketone
  • Method for preparing 6-difluoro alkyl ketone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Take a dry reaction tube, weigh allylbenzaldehyde 1a (36.5mg, 0.25mmol), phenylboronic acid 2a (37.0mg, 0.3mmol), ethyl difluorobromoacetate 3a (101mg, 0.5mmol), bis Triphenylphosphine palladium dichloride (7 mg, 0.01 mmol), cesium carbonate (122.2 mg, 0.375 mmol), and then 1 mL of dry dichloromethane were added to form a reaction system. The system was stirred at room temperature 25°C for 10 h, quenched by adding 10 mL of water, extracted three times with dichloromethane (10 mL), combined, the organic phase was washed with saturated edible water, and dried over anhydrous sodium sulfate. The organic phase was concentrated and separated by silica gel (300-400 mesh) column chromatography (eluent: petroleum ether / ethyl acetate volume ratio: 50 / 1) to obtain 70 mg of colorless liquid 4aaa, yield 81%. Product Spectrum Analysis 1 HNMR (600MHz, CDCl 3 )δ7.77–7.80(m,2H),7.55–7.62(m,1H),7.41–7.49(m,3H),7.26–7.35(m,3H),4.25(q,J=7.1Hz,2H) ,2.73(t,J=7.8Hz,2H),1.96–2.08(m,2H),1.72...

Embodiment 2

[0030] Except that the allyl benzaldehyde derivative shown in structural formula 1b is used to replace the allyl benzaldehyde shown in structural formula 1a in Example 1, all the other operating steps are the same as in Example 1, yield: 77%, colorless liquid; product Spectrum analysis 1 H NMR (600MHz, CDCl 3 )δ7.75–7.82(m,2H),7.60–7.65(m,1H),7.47–7.50(m,2H),7.38–7.44(m,1H),7.25–7.29(m,2H),4.26( q, J=7.2Hz, 2H), 2.67(t, J=7.8Hz, 2H), 1.95–2.06(m, 2H), 1.71–1.76(m, 2H), 1.30(t, J=7.1Hz, 3H ); 13 C NMR (151MHz, CDCl 3 )δ196.8,164.1(t,J=33.0Hz),140.0,138.5,137.0,133.7,131.6,131.5,130.4,130.1,128.7,128.4,116.0(t,J=250.4Hz),62.8,33.9(t,J =23.4Hz), 31.8, 23.2(t, J=4.2Hz), 13.9; 19 F NMR (565MHz, CDCl 3 )δ–105.9; HRMS (ESI) calcd for C 20 h 20 CIF 2 o 3 (M+H) + 381.1069, found 381.1081.

[0031] The reaction formula is as follows:

[0032]

Embodiment 3

[0034] Except that the allyl benzaldehyde derivative shown in structural formula 1c is used to replace the allyl benzaldehyde shown in structural formula 1a in Example 1, all the other operating steps are the same as in Example 1, yield: 81%, colorless liquid; product Spectrum analysis 1 H NMR (600MHz, CDCl 3 )δ7.74–7.79(m,2H),7.58–7.62(m,1H),7.44–7.49(m,2H),7.33(s,1H),7.26–7.26(m,2H),4.26(q, J=7.1Hz, 2H), 2.72(t, J=7.9Hz, 2H), 1.98–2.09(m, 2H), 1.72–1.81(m, 2H), 1.30(t, J=7.1Hz, 3H); 13 C NMR (151MHz, CDCl 3 )δ197.2, 164.1 (t, J = 32.9Hz), 142.6, 137.4, 136.6, 136.4, 133.5, 130.4, 130.1, 130.1, 128.5, 125.9, 116.0 (t, J = 250.3Hz), 62.8, 33.9 (t, J =23.3Hz), 32.2, 23.2(t, J=4.2Hz), 13.9; 19 F NMR (565MHz, CDCl 3 )δ–105.9; HRMS (ESI) calcd for C 20 h 20 CIF 2 o 3 (M+H) + 381.1069, found 381.1080.

[0035] The reaction formula is as follows:

[0036]

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Abstract

The invention discloses a method for preparing 6-difluoro alkyl ketone. The method includes mixing allylbenzene formaldehyde, phenylboronic acid, monobromo difluoro acetic ester, palladium catalysts, alkali and solvents with one another to form reaction systems; carrying out reaction and then treating reaction products to obtain the 6-difluoro alkyl ketone with the structure shown in a formula I. The structure of the allylbenzene formaldehyde is shown in a formula II. The method has the advantages that 1, n-hydrogen atom transfer radical addition strategies are applied to remote aryl difluoro alkylation for alkene, three-component reaction is completely carried out on monobromo difluoro methyl compounds, the allylbenzene formaldehyde and boric acid by means of palladium catalysis, accordingly, the 6-difluoro alkyl ketone can be synthesized by the aid of one-pot processes, reaction conditions are mild, the method is easy to implement and excellent in yield and has excellent theoretical value and an excellent application prospect, functional groups are good in compatibility, and substrates are wide in applicability.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a preparation method of 6-difluoroalkyl ketone. Background technique [0002] Due to the special properties of fluorine atoms, the introduction of fluorine-containing segments into organic molecules can often significantly change the acidity, lipophilicity, polarity, dipole moment, and chemical and biological metabolic stability of the parent. Therefore, fluorine-containing organic compounds have been widely used. to pharmaceuticals, pesticides and materials. Difluoromethylene (CF 2 ) compounds not only have the characteristics of general fluorine-containing compounds, but also have their own unique chemical properties and medicinal value. Difluoromethylene is the biological isoelectronic body of groups such as hydroxyl, mercapto and carbonyl, so the introduction of difluoromethylene into organic molecules will not change the molecular volume greatly. Not only that...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C67/347C07C69/738C07D317/54C07D333/22
CPCC07C67/347C07D317/54C07D333/22C07C69/738
Inventor 朱钢国聂新亮罗芳程存归郭冬梅
Owner ZHEJIANG NORMAL UNIVERSITY
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