1535-67-7Relevant academic research and scientific papers
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)
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.
SYNTHESE DE COMPOSES AROMATIQUES COMPORTANT LES GROUPEMENTS OCF2Br ET SCF2Br; I - Action du dibromodifluoromethane sur les thiophenate et phenate de potassium
Rico, Isabelle,Wakselman, Claude
, p. 323 - 326 (1981)
The synthesis of C6H5OCF2Br and C6H5SCF2Br from CF2Br2 is described.
SRN1 Substitutions of Halogenoperfluoroalkanes (CF3Br or CF2Cl2) under Pressure
Wakselman, Claude,Tordeux, Marc
, p. 793 - 794 (1984)
Radical chain fluoroalkylation of arenethiolates by CF3Br or CF2Cl2, performed under slight pressure in a glass apparatus, gives aryl polyfluoromethyl sulphides.
Direct S-difluoromethylation of thiols using the Ruppert-Prakash reagent Dedicated to Prof. Veronique Gouverneur on the occasion of receiving the ACS Award for Creative Work in Fluorine Chemistry.
Prakash, G.K. Surya,Krishnamoorthy, Sankarganesh,Kar, Sayan,Olah, George A.
, p. 186 - 191 (2015)
Direct S-difluoromethylation of aryl and aliphatic thiols using the Ruppert-Prakash reagent is demonstrated. The reaction produces trimethylsilyldifluoromethyl sulfides, which upon cleavage with fluoride produces the difluoromethyl sulfides. The key reaction features are the use of relatively inexpensive and commercially available starting materials, shorter reaction times, ambient temperatures, easy reaction procedure, and selective S-difluoromethylation in the presence of -OH, -NH2 and -CO2H functional groups. Furthermore, one-pot arylthiodifluoromethyl transfer to PhCHO is also demonstrated.
SYNTHESIS OF BROMODIFLUOROMETHYL PHENYL SULFIDE, SULFOXIDE AND SULFONE
Burton, Donald J.,Wiemers, Denise M.
, p. 573 - 582 (1981)
Sodium thiophenoxide reacts with dibromodifluoromethane to give bromodifluoromethyl phenyl sulfide.Peracid oxidation of the sulfide gives the corresponding sulfoxide and sulfone.The formation of the sulfide is suggested to proceed via attack of thiophenoxide on halogen to produce difluorocarbene.Capture of carbene by thiophenoxide followed by a second positive halogen abstraction reaction yields the sulfide, PhSCF2Br.The use of excess sodium thiophenoxide yields difluorobis(thiophenyl)methane, (PhS)2CF2, via a similar mechanistic scheme.
Reactivity of the Perhaloalkanes CF2X2 (X = Cl, Br) with Nucleophiles. 6. Coexistence of Carbene and Radical Processes Initiated by Single-Electron Transfer
Rixo, I.,Cantacuzene, D.,Wakselman, C.
, p. 1979 - 1982 (1983)
In the condensation of sodium thiophenoxide with CF2BrCl in DMF at -40 deg C, two mechanisms are involved simultaneously.A carbene chain process is postulated for the formation of C6H5SCF2Br and C6H5SCF2H.A radical chain process is implicated for the formation of C6H5SCF2Cl and C6H5SCF2SC6H5.These competitive chain processes could occur after an initial one-electron transfer from the thiophenoxide to CF2BrCl, giving a caged intimate radical/anion radical pair (RARP).
Synthesis of α-Difluoromethyl Aryl Ketones through a Photoredox Difluoromethylation of Enol Silanes
Arseniyadis, Stellios,Cambeiro, Xacobe C.,Selmi-Higashi, Elias,Zhang, Jinlei
supporting information, p. 4239 - 4243 (2021/06/28)
We report here an efficient and highly straightforward access to α-difluoromethylated ketones through a visible light-mediated difluoromethylation of readily available enol silanes. The method, which takes advantage of the polyvalence of Hu's reagent, N-tosyl-S-difluoromethyl-S-phenylsulfoximine, used here as a CHF2 radical precursor under catalytic photoredox conditions, is practical, scalable, and provides the corresponding α-CHF2 ketones in good to excellent yields.
C-H Electrophilic (phenylsulfonyl)difluoromethylation of (hetero)arenes with a newly designed reagent
Nobile, Enzo,Castanheiro, Thomas,Besset, Tatiana
supporting information, p. 12337 - 12340 (2021/12/07)
The synthesis of an original electrophilic difluoromethylating reagent was successfully achieved upon a straightforward protocol (3 steps). Like a Swiss army knife, this bench-stable reagent allowed the functionalization of various classes of compounds under mild and transition metal-free conditions. Hence, an efficient and operationally simple tool for the construction of C(sp2)-, C(sp3)- and S-CF2SO2Ph bonds was provided, expanding the chemical space of PhSO2CF2-containing molecules. Late-stage functionalization of bioactive molecules and the synthesis of PhSO2CF2- and HCF2-analogs of Lidocaine were also successfully achieved.
Regio- and chemoselectivity in S- and O- difluoromethylation reactions using diethyl (bromodifluoromethyl)phosphonate
Amir, Dafna,Binyamin, Iris,Drug, Eyal,Fridkin, Gil,Gershonov, Eytan,Marciano, Daniele,Redy-Keisar, Orit,Yehezkel, Lea,Zafrani, Yossi
, (2021/09/08)
The effective difluoromethylations of various S- and O- based- nucleophiles, presenting a wide range of pKa values, using diethyl(bromodifluoromethyl) phosphonate (1) under basic conditions is described. These reactions, which rely on the quantitative generation of difluorocarbene formed through the hydrolysis of 1, were found to be effective only once the starting materials had pKa values of less than ca. 11. Importantly, in cases in which the substrates held two or three nucleophilic centers this feature was successfully implemented to achieve a high chemo- or regioselective difluoromethylation of the center exhibiting the lowest pKa value and the highest polarizability.
Nickel-Catalyzed Decarbonylative Synthesis of Fluoroalkyl Thioethers
Brigham, Conor E.,Malapit, Christian A.,Lalloo, Naish,Sanford, Melanie S.
, p. 8315 - 8320 (2020/08/28)
This report describes the development of a nickel-catalyzed decarbonylative reaction for the synthesis of fluoroalkyl thioethers (RFSR) from the corresponding thioesters. Readily available, inexpensive, and stable fluoroalkyl carboxylic acids (RFCO2H) serve as the fluoroalkyl (RF) source in this transformation. Stoichiometric organometallic studies reveal that RF-S bond-forming reductive elimination is a challenging step in the catalytic cycle. This led to the identification of diphenylphosphinoferrocene as the optimal ligand for this transformation. Ultimately, this method was applied to the construction of diverse fluoroalkyl thioethers (RFSR), with R = both aryl and alkyl.
