Simplified syntheses suited for large scale preparations of the two hypervalent iodine reagents 1 and 2 for electrophilic trifluoromethylation are reported. In both cases, the stoichiometric oxidants ...sodium metaperiodate and tert-butyl hypochlorite have been replaced by trichloroisocyanuric acid. Reagent 1 is accessible in a one-pot procedure from 2-iodobenzoic acid in 72% yield. Reagent 2 was prepared via fluoroiodane 11 in a considerably shorter reaction time and with no need of an accurate temperature control.
Thanks to the advancements in computer power and capability of Computational Fluid Dynamics codes, the amount of research work on the numerical simulation of slurry flows in pipelines has increased ...exponentially in few years, opening the way to the use of this approach for engineering purposes. The Two Fluid Model (TFM), in which both phases are interpreted as interpenetrating continua and solved in the Eulerian, cell-based framework, allows the best compromise considering the engineering requirements of computational efficiency, applicability, and accuracy. However, the solution of this model is affected by several numerical and modelling factors, and, even if good agreement is achieved between simulation results and experimental measurements, it might be difficult to trust the predictions outside the validation conditions, thereby limiting the engineering potential of the two-fluid approach. The fully-suspended slurry flow in horizontal pipes was numerically simulated using the TFM recently developed by one of the authors of this paper, and the computational results were compared to experimental data reported in the literature. It has been clearly demonstrated that, even in this simple geometry, many possible sources of inaccuracy and uncertainty come into play. Whilst assessing their role, best practice guidelines and consistency checks were proposed to improve the accuracy of the estimates and increase the reliability of the TFM solution. Afterwards, pipe size-up scaling tests and a careful specification of the applicability conditions provided further confidence to the use of the TFM as a tool for engineering design.
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•Convergence and sensitivity assessment followed by calibration and validation.•Critical inspection of diffcult-to-measure parameters.•Investigation of pipe size-up scalability of a two-fluid model.•Precise specification of the application domain.•Development of best practice guidelines for slurry pipe flow simulation.
Granular flow is modelled under the following conditions: Steady-state uniform turbulent open-channel solid–liquid flow carrying combined load at high solids concentration above a plane mobile bed. ...In the combined load, a portion of transported particles is transported as collisional bed load and the rest as suspended load supported by carrier turbulence. In our modelling approach, we consider one-dimensional flow and take into account a layered structure of the flow with the intense combined load. Principles of kinetic theory of granular flow are employed together with the mixing-length theory of flow turbulence in order to predict distributions of solids concentration and velocity in sediment-water flow of the given flow depth and longitudinal slope in an open channel. Components of the model are tested and calibrated by results of our laboratory experiments with lightweight sediment in a recirculating tilting flume.
Evans-type chiral lithium imide enolates undergo diastereoselective α-trifluoromethylation with a hypervalent iodine–CF3 reagent with up to 91% combined isolated yield and 97:3 dr. The resulting ...isolated diastereopure products can be further transformed into valuable products without racemization.
Tetrafluoroalkyl bromides are metalated with equimolar iPrMgCl·LiCl (Turbo Grignard) to form organomagnesium compounds which are stable at low temperatures and react with various electrophiles ...(aldehydes, ketones, CO2, cyclic sulfate and sulfamidate, N-sulfonylimines, nitrone, chlorophosphate, nonaflyl azide) to afford novel functionalized tetrafluoroethylene-containing products. Ease of operation, excellent selectivity, high nucleophilicity, and enhanced stability of the reactive species together with a broad substrate scope comprise a highly attractive nucleophilic tetrafluoroethylation protocol affording unique synthetic building blocks.
A series of new hypervalent iodine reagents based on the 1,3‐dihydro‐3,3‐dimethyl‐1,2‐benziodoxole and 1,2‐benziodoxol‐3‐(1H)‐one scaffolds, which contain a functionalized tetrafluoroethyl group, ...have been prepared, characterized, and used in synthetic applications. Their corresponding electrophilic fluoroalkylation reactions with various sulfur, oxygen, phosphorus, and carbon‐centered nucleophiles afford products that feature a tetrafluoroethylene unit, which connects two functional moieties. A related λ3‐iodane that contains a fluorophore was shown to react with a cysteine derivative under mild conditions to give a thiol‐tagged product that is stable in the presence of excess thiol. Therefore, these new reagents show a significant potential for applications in chemical biology as tools for fast, irreversible, and selective thiol bioconjugation.
Fluoroalkylating agents: A series of new hypervalent iodine reagents that contain a functionalized tetrafluoroethyl group are prepared and used for electrophilic fluoroalkylations with S, O, P, and C nucleophiles (see scheme).
Fluoroalkylation reagents based on hypervalent iodine are widely used to transfer fluoroalkyl moieties to various nucleophiles. However, the transferred groups have so far been limited to simple ...structural motifs. We herein report a reagent featuring a secondary amine that can be converted to amide, sulfonamide, and tertiary amine derivatives in one step. The resulting reagents bear manifold functional groups, many of which would not be compatible with the original synthetic pathway. Exploiting this structural versatility and the known high reactivity toward thiols, the new‐generation reagents were used in bioconjugation with an artificial retro‐aldolase, containing an exposed cysteine and a reactive catalytic lysine. Whereas commercial reagents based on maleimide and iodoacetamide labeled both sites, the iodanes exclusively modified the cysteine residue. The study thus demonstrates that modular fluoroalkylation reagents can be used as tools for cysteine‐selective bioconjugation.
Bioconjugation—from iodine to sulfur: Modular fluoroalkylation reagents based on hypervalent iodine were used for cysteine‐selective labeling of an artificial enzyme without modifying its catalytic lysine, introducing a novel method for thiol bioconjugation.
Covalent labeling of proteins in combination with mass spectrometry has been established as a complementary technique to classical structural methods, such as X-ray, NMR, or cryogenic electron ...microscopy (Cryo-EM), used for protein structure determination. Although the current covalent labeling techniques enable the protein solvent accessible areas with sufficient spatial resolution to be monitored, there is still high demand for alternative, less complicated, and inexpensive approaches. Here, we introduce a new covalent labeling method based on fast fluoroalkylation of proteins (FFAP). FFAP uses fluoroalkyl radicals formed by reductive decomposition of Togni reagents with ascorbic acid to label proteins on a time scale of seconds. The feasibility of FFAP to effectively label proteins was demonstrated by monitoring the differential amino acids modification of native horse heart apomyoglobin/holomyoglobin and the human haptoglobin–hemoglobin complex. The obtained data confirmed the Togni reagent-mediated FFAP is an advantageous alternative method for covalent labeling in applications such as protein footprinting and epitope mapping of proteins (and their complexes) in general. Data are accessible via the ProteomeXchange server with the data set identifier PXD027310.
A mild trifluoromethylation reaction of N,N‐disubstituted hydroxylamines that is tolerant towards a variety of functional groups, including nitriles, alcohols, ketones, esters, amides, imides, and ...nitrogen heterocycles, is reported. The key feature of this reaction is the activation of the CF3 reagent with either trimethylsilyl triflate or LiClO4 and partial or full deprotonation of the substrate with tetramethylguanidine or lithium diisopropylamide. Products were obtained in up to 80 % yield. Preliminary mechanistic studies suggested that the reaction follows a radical pathway in which the deprotonated hydroxylamine and a Lewis or Brønsted acid activated CF3 reagent engages in a single‐electron‐transfer step to generate a pair of radicals that recombine to afford the desired product. The trifluoromethylation procedure was successfully used in the modification of secondary nitrogen groups of pharmaceutically relevant targets (Fluoxetine and Mefloquine), which afforded new derivatives containing a novel N‐trifluoromethoxy moiety.
Electrophilic trifluoromethylation of dialkyl hydroxylamines with hypervalent iodine(III) reagents gives access to compounds containing the virtually unexplored NOCF3 functional group. Aspects concerning synthesis, properties, and reaction mechanism are presented. The transformation is also applicable to hydroxylamines derived from common drugs and shows a broad functional group tolerance.
A new fluorinated azidoethane1-azido-1,1,2,2-tetrafluoroethanewas prepared in quantitative yield by the addition of an azide anion to tetrafluoroethylene in a protic medium. The title azide was ...shown to be thermally stable and insensitive to impact. Copper(I)-catalyzed 3 + 2 cycloaddition with alkynes afforded 4-substituted N-tetrafluoroethyl-1,2,3-triazoles which underwent rhodium(II)-catalyzed transannulation with nitriles to novel N-tetrafluoroethylimidazoles or the reaction with triflic acid to enamido triflates. 3 + 2 Cycloaddition of the title azide with primary amines afforded novel 5-difluoromethyl tetrazoles.
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