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

Novel synthesis method of gem-difluoroalkane and alpha-fluorocarboxylic acid

A technology for fluorinated carboxylic acid and difluoroalkane, which is applied in the field of novel synthesis of geminal difluoroalkane and α-fluorinated carboxylic acid, and can solve the problem that starting materials are difficult to obtain substrate range, poor functional group compatibility, harsh reaction conditions, etc. problems, to achieve good chemical selectivity and functional group compatibility, mild conditions, and simple raw materials.

Inactive Publication Date: 2019-05-31
NANJING UNIV OF TECH
View PDF2 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Aiming at the deficiencies of the prior art, the present invention provides a novel method for synthesizing gem-difluoroalkanes and α-fluorocarboxylic acids, which solves the problems in the prior art of harsh reaction conditions, poor functional group compatibility, and difficult starting materials Problems with access and limited substrate range

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
  • Novel synthesis method of gem-difluoroalkane and alpha-fluorocarboxylic acid
  • Novel synthesis method of gem-difluoroalkane and alpha-fluorocarboxylic acid
  • Novel synthesis method of gem-difluoroalkane and alpha-fluorocarboxylic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Synthesis of 1-chloro-4-(3,3-difluoropentyl)benzene (2a)

[0037] 2-(4-Chlorophenyl)-2-ethylmalonic acid (1a, 54.1mg, 0.2mmol), silver nitrate AgNO 3 (10.2mg, 0.06mmol), sodium benzoate PhCOONa (72mg, 0.5mmol), selective fluorine reagent Selectfluor (425.2mg, 1.2mmol), add to the reaction tube, replace N 2 , add acetonitrile / water / n-hexane=1 / 1 / 3 in total 3mL, set the reaction temperature to 55°C, and stir for 12 hours. The reaction was cooled to room temperature, 2 mL of 3M hydrochloric acid solution was added thereto, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, filtered, and the organic solvent was spin-dried, and the crude product was purified on a preparative silica gel plate (petroleum ether / acetic acid ethyl ester = 50 / 1). The product 1-chloro-4-(3,3-difluoropentyl)benzene was obtained as a colorless oil, yield: 26.2 mg (60%). 1 H NMR (400MHz, CDCl 3 ):δ7.26(d,J=8.4Hz,2H),7.13(d,J=8.4Hz,2H),2.83–2.72(m,2H...

Embodiment 2

[0039] Synthesis of 2,2-difluoro-1,3-diphenylpropane (2b)

[0040] 2,2-Dibenzylmalonic acid (1b, 56.8mg, 0.2mmol), silver nitrate AgNO 3 (10.2mg, 0.06mmol), sodium benzoate PhCOONa (72mg, 0.5mmol), selective fluorine reagent Selectfluor (425.2mg, 1.2mmol), add to the reaction tube, replace N 2 , add acetonitrile / water / n-hexane=1 / 1 / 3 in total 3mL, set the reaction temperature to 55°C, and stir for 12 hours. The reaction was cooled to room temperature, 2 mL of 3M hydrochloric acid solution was added thereto, extracted with ethyl acetate, the organic phases were combined, dried with anhydrous sodium sulfate, filtered, and the organic solvent was spin-dried, and the crude product was purified on a preparative silica gel plate (petroleum ether / acetic acid ethyl ester = 50 / 1). The product 2,2-difluoro-1,3-diphenylpropane was obtained as a colorless oil, yield: 27.8 mg (60%). 1 H NMR (400MHz, CDCl 3 ):δ7.36–7.16(m,10H),3.09(t,J=16.4Hz,4H). 19 F NMR (376MHz, CDCl 3 ):δ-94.6–-94....

Embodiment 3

[0042] Synthesis of 5,5-Difluorohexylbenzene (2c)

[0043] 2-Methyl-2-(4-phenylbutyl)malonic acid (1c, 50.1mg, 0.2mmol), silver nitrate AgNO 3 (10.2mg, 0.06mmol), sodium benzoate PhCOONa (100.8mg, 0.7mmol), selective fluorine reagent Selectfluor (425.2mg, 1.2mmol), add to the reaction tube, replace N 2 , add acetonitrile / water / n-hexane=1 / 1 / 3 total 5mL, set the reaction temperature to room temperature, and stir for 12 hours. 2 mL of 3M hydrochloric acid solution was added thereto, extracted with ethyl acetate, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the organic solvent was spin-dried, and the crude product was purified on a preparative silica gel plate (petroleum ether / ethyl acetate=50 / 1 ). The product 5,5-difluorohexylbenzene was obtained as a colorless oil, yield: 28.5 mg (72%). 1 H NMR (400MHz, CDCl 3 ):δ7.31–7.25(m,2H),7.21–7.15(m,3H),2.63(t,J=7.6Hz,2H),1.93–1.79(m,2H),1.71–1.62(m,2H ),1.62–1.47(m,5H). 19 F NMR (376MHz, CDC...

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
Melting pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a novel synthesis method of gem-difluoroalkane and alpha-fluorocarboxylic acid. The synthesis method comprises following steps: step one, carrying out salt forming reactions between one carboxylic acid of propane diacid derivatives and monovalent silver to obtain silver carboxylate, and then oxidizing silver carboxylate by a fluorine reagent to obtain divalent silver salts;step two, oxidizing carboxylic acid by divalent silver salts to remove one CO2 molecule to form an alpha-carboxylic acid free radical; and step three, under a difluoro- condition, making alpha-fluorocarboxylic acid carry out decarboxylation and fluorination reactions to obtain gem-difluoroalkane. The invention relates to the technical field of organic fluorine compounds. According to the novel synthesis method, by adjusting the alkalis and solvents, under the catalytic action of monovalent silver, propane diacid derivatives R1C(COOH)2R2 and a fluorine reagent carry out reactions to selectively generate gem-difluoroalkane R1CF2R2 and alpha-fluorocarboxylic acid R1CF(COOH)R2; the operation is simple, the raw materials are cheap and can be easily prepared, the reaction conditions are mild, the chemical selectivity and the functional group compatibility are good, and the method is very practical.

Description

technical field [0001] The invention relates to the technical field of organic fluorine compounds, in particular to a novel method for synthesizing gem-difluoroalkanes and alpha-fluorocarboxylic acids. Background technique [0002] The gem-difluoromethylene functional group has unique properties such as enhancing the metabolic stability of the parent molecule and enhancing the acidity of adjacent groups, so the introduction of difluoromethylene into small molecules can change its physical and chemical properties, so many drugs and have Biologically active compounds contain gem-difluoromethylene functional groups. Although people have made great progress in the preparation of aryl-substituted gem-difluorochemicals, there are still few methods for synthesizing gem-difluoroalkanes. Conventional methods for preparing synthetic gem-difluoroalkanes include: deoxyfluorination of ketones [1.L.N.Markovskij, V.E.Pashinnik, A.V.Kirsanov, Synthesis 787-789 (1973); 2.W.J.Middleton, J.Or...

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
IPC IPC(8): C07C17/093C07C25/13C07C22/08C07C19/08C07C51/363C07C63/70C07D209/48C07C67/307C07C69/63C07C45/63C07C49/167C07C253/30C07C255/50C07C315/04C07C317/14C07D211/38C07C41/22C07C43/12C07C49/80C07C29/62C07C33/46C07C57/58C07C59/21C07C255/57C07D211/66C07C59/135C07C59/88C07C59/56
Inventor 陈建平王震郭聪颖杨城
Owner NANJING UNIV OF TECH
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

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com