156570-16-0Relevant articles and documents
Difluoromethyl bioisostere: Examining the lipophilic hydrogen bond donor concept
Zafrani, Yossi,Yeffet, Dina,Sod-Moriah, Gali,Berliner, Anat,Amir, Dafna,Marciano, Daniele,Gershonov, Eytan,Saphier, Sigal
, p. 797 - 804 (2017/02/05)
There is a growing interest in organic compounds containing the difluoromethyl group, as it is considered a lipophilic hydrogen bond donor that may act as a bioisostere of hydroxyl, thiol, or amine groups. A series of difluoromethyl anisoles and thioanisoles was prepared and their druglike properties, hydrogen bonding, and lipophilicity were studied. The hydrogen bond acidity parameters A (0.085-0.126) were determined using Abraham's solute 1H NMR analysis. It was found that the difluoromethyl group acts as a hydrogen bond donor on a scale similar to that of thiophenol, aniline, and amine groups but not as that of hydroxyl. Although difluoromethyl is considered a lipophilicity enhancing group, the range of the experimental Δlog P(water-octanol) values (log P(XCF2H) - log P(XCH3)) spanned from -0.1 to +0.4. For both parameters, a linear correlation was found between the measured values and Hammett σ constants. These results may aid in the rational design of drugs containing the difluoromethyl moiety.
Xenon Difluoride Mediated Fluorodecarboxylations for the Syntheses of Di- and Trifluoromethoxyarenes
Chatalova-Sazepin, Claire,Binayeva, Meruyert,Epifanov, Maxim,Zhang, Wei,Foth, Paul,Amador, Carolyn,Jagdeo, Manu,Boswell, Benjamin R.,Sammis, Glenn M.
, p. 4570 - 4573 (2016/09/28)
XeF2 is demonstrated to be a more proficient fluorine-transfer reagent than either NFSI or Selectfluor in fluorodecarboxylations of both mono- and difluoroaryloxy acetic acid derivatives. This method efficiently converts a wide range of neutral and electron-poor substrates to afford the desired di- and trifluoromethyl aryl ethers in good to excellent yields. The purifications are facile, and the reaction times are less than 5 min, which makes these fluorodecarboxylations promising for future PET-imaging applications.
18F-Labeling of Aryl-SCF3, -OCF3 and -OCHF2 with [18F]Fluoride
Khotavivattana, Tanatorn,Verhoog, Stefan,Tredwell, Matthew,Pfeifer, Lukas,Calderwood, Samuel,Wheelhouse, Katherine,Leecollier, Thomas,Gouverneur, Vronique
supporting information, p. 9991 - 9995 (2015/08/19)
We report that halogenophilic silver(I) triflate permits halogen exchange (halex) nucleophilic 18F-fluorination of aryl-OCHFCl, -OCF2Br and -SCF2Br precursors under mild conditions. This AgI-mediated process allows for the first time access to a range of 18F-labeled aryl-OCHF2, -OCF3 and -SCF3 derivatives, inclusive of [18F]riluzole. The 18F-labeling of these medicinally important motifs expands the radiochemical space available for PET applications. A halogen exchange (halex) 18F-fluorination process offers access for the first time to 18F-labeled arylOCF3, arylOCHF2 and arylSCF3, three motifs of established medicinal importance in PET radiotracers. The use of silver(I) triflate is critical to permit 18F-labeling under mild conditions.
IMPROVEMENT OF THE SYNTHESIS OF ARYL DIFLUOROMETHYL ETHERS AND THIOEHTERS BY USING A SOLID-LIQUID PHASE-TRANSFER TECHNIQUE
Langlois, Bernard R.
, p. 247 - 262 (2007/10/02)
A new solid-liquid phase-transfer technique has been used to synthesize aryl difluoromethyl ehters and thioethers.Phenols (or thiophenols) and chlorodifuoromethane, dissolved in a cheap aprotic solvent of low polarity, are contacted with solid sodium hydroxide in the presence of a catalytic amount of tris-(3,6-dioxaheptyl)amine.The work-up of the reaction mixtures is very simple.Although yields are similar in both homogeneous and heterogeneous procedures using phenols, improved yields are obtained for thiophenols when using phase-transfer conditions.
