- A simple method for the synthesis of: N -difluoromethylated pyridines and 4-pyridones/quinolones by using BrCF2COOEt as the difluoromethylation reagent
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We describe a novel transition metal-free method for the synthesis of N-difluoromethylated pyridines and 4-pyridones/quinolones by using readily available ethyl bromodifluoroacetate as a fluorine source. The formation of N-difluoromethylated pyridines involves a two-step process in which N-alkylation by ethyl bromodifluoroacetate is followed by in situ hydrolysis of the ester and decarboxylation. Besides optimizing the N-difluoromethylation conditions and assessing the influence of steric and electronic effects on the outcome of the reaction, we have synthesized the N-difluoromethylated analogues of two fluorophores and demonstrated that their spectroscopic properties can be improved through replacement of N-CH3 group by N-CF2H. This journal is
- El Fakiri, Mohamed,Gandioso, Albert,Marchán, Vicente,Rovira, Anna
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- Facile new method for synthezising N-polyfluoroalkylated heterocycles - Molecular structure of N-(bromodifluoromethyl)-4-dimethylaminopyridinium bromide
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Carbon-bromine bond cleavage is observed when 4-dimethylaminopyridine is treated with CF2Br2 and BrCF2CF2Br to yield N-(bromodifluoromethyl) and N-(2-bromo-1,1,2,2-tetrafluoromethyl)pyridinium bromides, 1-Br and 2-Br, which are reductively debrominated using Bu3SnH and fluorinated by anhydrous Me4N+F-; the molecular structure of 1-Br is determined by single crystal X-ray crystallography to reveal a partial quinoidal character in the pyridine system and a hypervalent Br-...BrCF2 pairing.
- Kolomeitsev, Alexander,Schoth, Ralph-Matthias,Lork, Enno,Roeschenthaler, Gerd-Volker
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- Direct Synthesis of N-Difluoromethyl-2-pyridones from Pyridines
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A novel method for the synthesis of N-difluoromethyl-2-pyridones was described. This protocol enables the synthesis of N-difluoromethyl-2-pyridones from readily available pyridines using mild reaction conditions that are compatible with a wide range of functional groups. The preliminary mechanistic study revealed that N-difluoromethylpyridinium salts were the key intermediates to complete this conversion.
- Zhou, Sen,Hou, Xiaoya,Yang, Kai,Guo, Minjie,Zhao, Wentao,Tang, Xiangyang,Wang, Guangwei
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- Metal-Free Difunctionalization of Pyridines: Selective Construction of N-CF2H and N-CHO Dihydropyridines
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The reactivity of N-difluoromethylpyridinium salts is seldom explored because of their instability and low availability. Here we present a novel nucleophilic addition of N-difluoromethylpyridinium salts with nitroalkanes to synthesize N-CF2H-dihydropyridines and N-CHO-dihydropyridines in a highly efficient and regioselective pathway. This protocol exhibits good functional group tolerance and good to excellent yields.
- Zhou, Sen,Sun, Ze-Ying,Zhu, Kongying,Zhao, Wentao,Tang, Xiangyang,Guo, Minjie,Wang, Guangwei
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- Chemoselective N-Difluoromethylation of Functionalized Tertiary Amines
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A practical, convenient, and general method for the difluoromethylation of tertiary amines, using diethyl bromodifluoromethylphosphonate and fluoride, is described. This commercially available phosphonate smoothly reacts with a fluoride ion to liberate a difluorocarbene intermediate that in the presence of a proton source and a tertiary amine generates the corresponding α-difluoromethylammonium compound in good to excellent yields. Despite the involvement of a difluorocarbene intermediate, this difluoromethylation occurs almost exclusively on the nitrogen atom with diverse molecular structures, including drugs, surfactants, chiral phase transfer catalysts, polymers, ionic liquids, and other fine chemicals. A preliminary assessment of the effects that an α-difluoromethyl groupT has on hydrogen bonding and logP of quaternary ammonium salts is also described.
- Zafrani, Yossi,Amir, Dafna,Yehezkel, Lea,Madmon, Moran,Saphier, Sigal,Karton-Lifshin, Naama,Gershonov, Eytan
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p. 9180 - 9187
(2016/10/18)
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- Generation of heteroarylium-N-difluoromethylides and heteroaryl-N-difluoromethyl anions and their reactions with electrophiles: Heteroaryl- and heteroarylium-N-difluoromethyl trimethylsilanes and a new heteroaryl-N-trifluoromethane
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Reductive debromination of N-bromodifluoromethyl-4-dimethylaminopyridinium bromide, 1-bromodifluoromethyl-imidazole, 1-methyl-3-bromodifluoromethyl-imidazolium bromide and 1-bromodifluoromethyl-2-methyl-benzimidazole using tetrakis(dimethylamino)ethylene (TDAE) or tris(diethylamido)phosphite leads to new fluorinated carbanionic species, namely heteroarylium-N-difluoromethylides and heteroaryl-N-difluoromethyl anions. In the presence of electrophiles such as benzaldehyde, chlorodiphenylphosphine and chlorotrimethylsilane, the corresponding heteroarylium- and heteroaryl-N-difluoromethylated derivatives, imidazole-N-difluoromethyl-phosphines and -silanes, 2-methyl-benzimidazole-N-difluoromethyltrimethyl-carbinols-phosphines and -silanes were obtained. Similar 4-dimethylaminopyridinium derivatives were synthesized.
- Bissky, German,Roeschenthaler, Gerd-Volker,Lork, Enno,Barten, Jan,Medebielle, Maurice,Staninets, Vasilij,Kolomeitsev, Alexander A.
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p. 173 - 181
(2007/10/03)
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