109801-24-3Relevant academic research and scientific papers
Controlling reactivity through liquid assisted grinding: The curious case of mechanochemical fluorination
Howard, Joseph L.,Sagatov, Yerbol,Repusseau, Laura,Schotten, Christiane,Browne, Duncan L.
, p. 2798 - 2802 (2017)
We have identified an example of a mechanochemically milled organic reaction where liquid-assisted grinding controls the selectivity, such a phenomenon has not been reported/observed before. It was found that upon milling dibenzoylmethane with Selectfluor in the absence of any solvent, a 3:1 ratio of monofluorinated:difluorinated product was observed. Whereas, addition of 0.125 mL of acetonitrile (～10% of the total volume of materials present) to the ground reaction mixture afforded 50:1 selectivity. Furthermore, this phenomenon is applicable to a small range of diketone substrates thus far explored. Additionally, we have demonstrated that difluorination can be achieved by simply switching from adding acetonitrile to addition of sodium carbonate. Most notable, in the latter case, is the reduced reaction time compared to a conventional solvent approach, 2 hours in the mill and 24 hours in the flask.
Translating solid state organic synthesis from a mixer mill to a continuous twin screw extruder
Cao, Qun,Howard, Joseph L.,Crawford, Deborah E.,James, Stuart L.,Browne, Duncan L.
, p. 4443 - 4447 (2018)
A study on the translation of a solid-state synthetic reaction from a mechanochemical mixer-mill to a continuous twin-screw extruder is discussed herein. The study highlights some considerations to be made and parameters to be tested in the context of a model fluorination reaction, which is the first organic fluorination to be attempted using extrusion. Upon optimization, which features the first use of grinding auxiliary solids to enable effective synthetic extrusion, the difluorination reaction was successfully translated to the extruder, leading to a 100-fold improvement in Space Time Yield (STY); 29 kg m-3 day-1 in a mixer mill to 3395 kg m-3 day-1 in a twin screw extruder.
Enolization rates control mono-: Versus di-fluorination of 1,3-dicarbonyl derivatives
Rozatian, Neshat,Beeby, Andrew,Ashworth, Ian W.,Sandford, Graham,Hodgson, David R.W.
, p. 10318 - 10330 (2019)
Fluorine-containing 1,3-dicarbonyl derivatives are essential building blocks for drug discovery and manufacture. To understand the factors that determine selectivity between mono- and di-fluorination of 1,3-dicarbonyl systems, we have performed kinetic studies of keto-enol tautomerism and fluorination processes. Photoketonization of 1,3-diaryl-1,3-dicarbonyl derivatives and their 2-fluoro analogues is coupled with relaxation kinetics to determine enolization rates. Reaction additives such as water accelerate enolization processes, especially of 2-fluoro-1,3-dicarbonyl systems. Kinetic studies of enol fluorination with Selectfluor and NFSI reveal the quantitative effects of 2-fluorination upon enol nucleophilicity towards reagents of markedly different electrophilicity. Our findings have important implications for the synthesis of α,α-difluoroketonic compounds, providing valuable quantitative information to aid in the design of fluorination and difluorination reactions.
Mild and selective α-fluorination of carbonyl compounds (ketones, 1,3-diketones, β-ketoesters, α-nitroketones, and β-ketonitriles) with Selectfluor (F-TEDA-BF4) in imidazolium ILs [BMIM/PF6 or BMIM/NTf2] with Br?nsted-acidic IL [PMIM(SO3H)/OTf] as promoter
Reddy, A. Srinivas,Laali, Kenneth K.
, p. 5495 - 5499 (2015)
Structurally diverse ketones, 1,3-diketones, and β-ketoesters, were selectively monofluorinated with Selectfluor (F-TEDA-BF4) (1 equiv) in [BMIM][PF6] as solvent and [PMIM(SO3H)][OTf] as promoter under mild conditions. In selected cases, the monofluorinated products were transformed to the gem-difluoro derivatives by employing an additional equivalent of Selectfluor, and gem-difluoro-derivatives were synthesized directly from the substrates by employing 2 equiv of Selectfluor. The method was extended to monofluorination of representative α-nitroketones and β-ketonitriles using [BMIM][NTf2] without the need for promoters. The described method offers the added advantage of recycling and reuse of the IL solvent. (Chemical Equation Presented).
Electrochemical fluorination of β-dicarbonyl compounds using p-iodotoluene difluoride as a mediator
Hara, Shoji,Hatakeyama, Tsuyoshi,Chen, Sheng-Qi,Ishi-I, Kenji,Yoshida, Masanori,Sawaguchi, Masanori,Fukuhara, Tsuyoshi,Yoneda, Norihiko
, p. 189 - 192 (1998)
The selective and direct introduction of the fluorine atom into the α-position of β-dicarbonyl compounds was electrochemically achieved using iodotoluene difluoride as the mediator. The resulting α-fluoro-β-dicarbonyl compounds are important building blocks for biologically active compounds.
Catalytic fluorination of 1,3-dicarbonyl compounds using iodoarene catalysts
Kitamura, Tsugio,Muta, Kazutaka,Kuriki, Satoshi
, p. 6118 - 6120 (2013)
Catalytic fluorination of 1,3-dicarbonyl compounds with aqueous hydrofluoric acid proceeded efficiently with the aid of iodoarene catalysts in the presence of m-CPBA as a terminal oxidant. o-Iodotoluene, o-iodoanisole, and o-ethyliodobenzene showed a high
1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate): An electrophilic fluorinating agent
Poss, Andrew J.,Shia, George A.
, p. 2673 - 2676 (1999)
1-Fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate), NFTh, is a electrophilic fluorinating that can be used to fluorinate aromatic rings, olefins, dienol acetates and enol ethers. When NFTh is reacted with an active methylene compound in the presence of ZnCl2, the corresponding mono- or di-fluoro derivative can be isolated.
Efficient Electrophilic Fluorination of β-Dicarbonyl Compounds with the Selectfluor Reagent F-TEDA-BF4 octane bis(tetrafluoroborate)>
Banks, R. Eric,Lawrence, Nicholas J.,Popplewell, Allan L.
, p. 343 - 344 (1994)
1,3-Dicarbonyl compounds (acyclic and cyclic 1,3-diketones, β-ketoesters, β-ketoamides) are converted efficiently to 2-monofluoro derivatives, and thence to 2,2-difluoro derivatives, with 1-chloromethyl-4-fluoro-1,4-diazoniabicyclooctane bis(tetrafluoroborate).
Organocatalytic Asymmetric Cascade Michael-acyl Transfer Reaction between 2-Fluoro-1,3-diketones and Unsaturated Thiazolones: Access to Fluorinated 4-Acyloxy Thiazoles
Biswas, Rayhan G.,Ray, Sumit K.,Unhale, Rajshekhar A.,Singh, Vinod K.
, p. 6504 - 6509 (2021)
Quinine derived bifunctional urea catalyzed cascade Michael-acyl transfer reaction of 5-alkenyl thiazolones and monofluorinated β-diketones has been developed. The fluorine containing 4-acyloxy thiazoles were synthesized in high yields and good diastereo-and excellent enantioselectivities. Synthetic transformations, including synthesis of 4-hydroxy thiazoles, have been demonstrated.
Microwave-assisted rapid electrophilic fluorination of 1,3-dicarbonyl derivatives with Selectfluor
Xiao, Ji-Chang,Shreeve, Jean'ne M.
, p. 475 - 478 (2005)
A microwave-assisted fluorination method for 1,3-dicarbonyl compounds using Selectfluor has been developed. 2-Monofluorinated products can be obtained in high yield in neutral reaction conditions with addition of 1 eq. of Selectfluor. Treatment of 1,3-dicarbonyls with 3 eq. of Selectfluor in the presence of tetrabutylammonium hydroxide (TBAH) as the base results in the formation of 2,2-difluorinated derivatives only.
