22225-77-0Relevant academic research and scientific papers
Difluoromethylation of alcohols with TMSCF2Br in water: A new insight into the generation and reactions of difluorocarbene in a two-phase system
Zhang, Rongyi,Ni, Chuanfa,Xie, Qiqiang,Hu, Jinbo
supporting information, (2020/11/10)
Although many difluorocarbene-involved reactions can be performed in the presence of water, the reaction of difluorocarbene using water as the only reaction medium is rare. By using TMSCF2Br as a unique difluorocarbene reagent and KHF2 as a mild activator, the difluoromethylation of liquid alcohols in water is described. This research not only develops an environmentally benign process for the synthesis of difluoromethyl ethers, but also provides a new insight into the generation and reactions of difluorocarbene in an oil-water two-phase system.
Triple Mode of Alkylation with Ethyl Bromodifluoroacetate: N, or O-Difluoromethylation, N-Ethylation and S-(ethoxycarbonyl)difluoromethylation
Polley, Arghya,Bairy, Gurupada,Das, Pritha,Jana, Ranjan
supporting information, p. 4161 - 4167 (2018/09/21)
In this report, we have explored a triple mode of chemical reactivity of ethyl bromodifluoroacetate. Typically, bromodifluoroacetic acid has been used as a difluorocarbene precursor for difluoromethylation of soft nucleophiles. Here we have disclosed nucleophilicity and base dependent divergent chemical reactivity of ethyl bromodifluoroacetate. It furnishes lithium hydroxide and cesium carbonate promoted difluoromethylation of tosyl-protected aniline and electron-deficient phenols respectively. Interestingly, switching the base from lithium hydroxide to 4-N,N-dimethylamino pyridine (DMAP) tosyl-protected anilines afforded the corresponding N-ethylation product. Whereas, highly nucleophilic thiophenols furnished the corresponding S-carboethoxydifluoromethylation product via a rapid SN2 attack to the bromine atom prior to the ester hydrolysis. This mechanistic divergence was established through several control experiments. It was revealed that difluoromethylation reaction proceeds through a tandem in situ ester hydrolysis/decarboxylative-debrominative difluorocarbene formation and subsequent trapping by the soft nucleophile-NHTs or electron-deficient phenolic ?OH groups. In the presence of DMAP the hydrolysis of the ester is perturbed instead a nucleophilic attack at the ethyl moiety provides the N-ethylation product. Hence, besides the development of a practical base-promoted N-difluoromethylation of amines and electron-deficient phenols, divergent reactivity pattern of inexpensive and user-friendly ethyl bromodifluoroacetate has been explored. (Figure presented.).
Visible-Light Photoredox Difluoromethylation of Phenols and Thiophenols with Commercially Available Difluorobromoacetic Acid
Yang, Jinyan,Jiang, Min,Jin, Yunhe,Yang, Haijun,Fu, Hua
supporting information, p. 2758 - 2761 (2017/05/24)
A simple and efficient visible-light photoredox one-pot method for difluoromethylation of phenols and thiophenols has been developed. The protocol uses commercially available, inexpensive, and easy handling difluorobromoacetic acid as the difluoromethylating agent, and the diverse O- and S-difluoromethylated products were prepared in good yields with tolerance of many functional groups.
Difluoro methylation reagent, preparation method and application thereof (by machine translation)
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Paragraph 0514; 0515; 0516; 0521; 0522; 0523, (2017/10/23)
The present invention discloses a two-trifluoromethylation of the reagent, preparation method and application thereof. The invention [...] methylation reagent preparation process is simple, high yield; and the reagent can be a more moderate, high-efficiently the sulfonic acid, alcohol, carbonyl and on the α carbon atom of the difluoromethyl. (by machine translation)
Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl]
Lin, Xiaoxi,Hou, Chuanqi,Li, Haohong,Weng, Zhiqiang
supporting information, p. 2075 - 2084 (2016/02/12)
This article describes the new economic decarboxylative trifluoromethylating reagent [Cu(phen)(O2CCF3)] (1; phen=1,10-phenanthroline) and the efficient difluorocarbene precursor [Cu(phen)2][O2CCF2Cl] (2). Treatment of copper tert-butoxide with phen and subsequent addition of trifluoroacetic acid or chlorodifluoroacetic acid afforded air-stable complexes 1 and 2, respectively, which were characterized by X-ray crystallography. The copper(I) ion in 1 is coordinated by a bidentate phen ligand, a monodentate trifluoroacetate group, and a molecule of CH3CN in a distorted tetrahedral coordination geometry. The molecular structure of 2 adopts an ionic form that consists of a [Cu(phen)2]+ cation and a chlorodifluoroacetate anion. Complex 1 reacted with a variety of aryl and heteroaryl halides to form trifluoromethyl (hetero)arenes in good yields. The corresponding Hammett plot exhibited a linear relationship and a reaction parameter (ρ)=+0.56±0.02, which indicated that the trifluoromethylation reaction proceeded via a nucleophilic reactive species. Complex 2 reacts with phenols to produce aryl difluoromethyl ethers in modest-to-excellent yields. Mechanistic investigations revealed that the difluoromethylation reaction proceeds by initial copper-mediated formation of difluorocarbene and subsequent concerted addition of difluorocarbene to the phenol to form a three-center transition state.
Use of fluoroform as a source of difluorocarbene in the synthesis of N-CF2H heterocycles and difluoromethoxypyridines
Thomoson, Charles S.,Wang, Linhua,Dolbier, William R.
, p. 34 - 39 (2015/03/04)
Fluoroform is used as a source of difluorocarbene to convert various N-, O-, and C-nucleophiles to their difluoromethylated derivatives. Imidazole, benzimidazole, benztriazole, hydroxypyridines, and their derivatives underwent reaction at moderate temperatures and atmospheric pressure, using potassium hydroxide as base in a two-phase (water/acetonitrile) process to provide moderate to good yields of the respective products. Nitrophenols required addition of a co-solvent (methanol) to obtain good yields of products.
Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine
Wang, Fei,Li, Lingchun,Ni, Chuanfa,Hu, Jinbo
supporting information, p. 344 - 351 (2014/03/21)
Background: 1,1-Difluoroalkenes cannot only be used as valuable precursors for organic synthesis, but also act as bioisosteres for enzyme inhibitors. Among various methods for their preparation, the carbonyl olefination with difluoromethylene phosphonium ylide represents one of the most straightforward methods. Results: The combination of (chlorodifluoromethyl)trimethylsilane (TMSCF2Cl) and triphenylphosphine (PPh3) can be used for the synthesis of gem-difluoroolefins from carbonyl compounds. Comparative experiments demonstrate that TMSCF2Cl is superior to (bromodifluoromethyl)trimethylsilane (TMSCF2Br) and (trifluoromethyl)trimethylsilane (TMSCF3) in this reaction. Conclusion: Similar to many other Wittig-type gem-difluoroolefination reactions in the presence of PPh3, the reaction of TMSCF2Cl with aldehydes and activated ketones is effective.
Three step procedure for the preparation of aromatic and aliphatic difluoromethyl ethers from phenols and alcohols using a chlorine/fluorine exchange methodology
Dolbier Jr., William R.,Wang, Fei,Tang, Xiaojun,Thomoson, Charles S.,Wang, Linhua
, p. 72 - 76 (2014/03/21)
Difluoromethyl ethers are prepared from phenols in three steps via their respective formate ester derivatives. The formates are first converted to dichloromethyl ethers by treatment with PCl5. These ethers are then induced to undergo chlorine/fluorine exchange to form the respective difluoromethyl ethers. The chlorine/fluorine exchange is carried out by either a room temperature, solvolytic process using THF-5HF or Et3N-3HF as exchange medium, where HF is the ultimate source of fluorine, or by a direct displacement process in sulfolane at 125 C, where KF is the source of fluorine. By one or another of these processes, virtually all phenols, electron-rich and electron-poor, can be converted to their respective difluoromethyl ethers in good yields. Aliphatic alcohols are also able to be converted to their difluoromethyl ether derivatives using the Et3N-3HF exchange medium.
SYNTHESIS OF DIFLUOROMETHYL ETHERS AND SULFIDES
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Paragraph 0078-0082; 00123-00126, (2014/07/22)
The synthesis of difluoromethyl ethers and sulfides with a simple, non-ozone- depleting reagent is described. The difluoromethylation of phenols with this reagent occurs at room temperature within minutes with exceptional functional group tolerance. The mild conditions makes possible tandem processes for the conversion of aryl boronic acids, aryl halides and arenes to difluoromethyl ethers. Mechanistic studies support a reaction pathway involving nucleophilic attack of the phenolate to difluorocarbene.
Synthesis of gem-difluorocyclopropa(e)nes and O-, S-, N-, and P-difluoromethylated compounds with TMSCF2Br
Li, Lingchun,Wang, Fei,Ni, Chuanfa,Hu, Jinbo
supporting information, p. 12390 - 12394 (2013/12/04)
Two-in-one: Me3SiCF2Br is an efficient difluorocarbene source and is compatible with both neutral and aqueous basic conditions. Bromide-ion-initiated [2+1] cycloaddition with alkenes/alkynes and hydroxide ion promoted α-addition with (thio)phenols, (thio)alcohols, sulfinates, heterocyclic amines, and H-phosphine oxides give the corresponding gem-difluorinated compounds with broad functional-group tolerance. Copyright
