3,972 research outputs found
Mechanochemistry as an emerging tool for molecular synthesis: what can it offer?
Mechanochemistry is becoming more widespread as a technique for molecular synthesis with new mechanochemical reactions being discovered at increasing frequency. Whilst mechanochemical methods are solvent free and can therefore lead to improved sustainability metrics, it is more likely that the significant differences between reaction outcomes, reaction selectivities and reduced reaction times will make it a technique of interest to synthetic chemists. Herein, we provide an overview of mechanochemistry reaction examples, with âdirectâ comparators to solvent based reactions, which collectively seemingly show that solid state grinding can lead to reduced reaction times, different reaction outcomes in product selectivity and in some instances different reaction products, including products not accessible in solution
Continuous flow synthesis of antimalarials: opportunities for distributed autonomous chemical manufacturing
The concept of distributed manufacturing of chemicals is presented and discussed, with specific focus on the context of preparing molecules that can combat the development of geographically-localised resistant strains of infectious pathogens. Specifically we present the case of antimalarial compounds and demonstrate that the flow chemistry community have already designed both a machine capable of distrubuted chemical manufacturing and a module that would be capable of producing artemisin derivatives at the point of use
Mechanochemical electrophilic fluorination of liquid beta-ketoesters
An improved substrate scope for the mechanochemical electrophilic fluorination of dicarbonyls is reported. The applicable substrates have now been broadened to include liquid β-ketoesters. Key to this capability is the inclusion of a grinding auxiliary (NaCl) to improve mass transfer and prevent pasting or gumming of the reaction mixture. Notably, the use of a small amount of acetonitrile is critical to increasing the rate of reaction, ensuring complete consumption of starting materials during the short reaction times as well as improving the selectivity for the monofluorinated product in the mill
Mechanochemical Activation of Zinc and Application to Negishi Cross-Coupling
A form independent activation of zinc, concomitant generation of organozinc species and engagement in a Negishi crossâcoupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp3)âC(sp2) and C(sp2)âC(sp2) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the inâ
situ generation organometallic compounds from base metals and their concomitant engagement in synthetic reactions via mechanochemical methods
Preparation of difluoromethylthioethers through difluoromethylation of disulfides using TMS-CF2H
We report an operationally simple, metal-free approach for the late-stage introduction of the important lipophilic hydrogen-bond donor motif, SCF2H. This reaction converts diaryl- and dialkyl-disulfides into the corresponding aryl/alkylâSCF2H through the nucleophilic transfer of a difluoromethyl group with good functional group tolerance. This method is notable for its use of commercially available TMSCF2H, and does not rely on the need for handling of sensitive metal complexes
One-pot multistep mechanochemical synthesis of fluorinated pyrazolones
Solventless mechanochemical synthesis represents a technique with improved sustainability metrics compared to solvent-based processes. Herein, we describe a methodical process to run one solventless reaction directly into another through multistep mechanochemistry, effectively amplifying the solvent savings. The approach has to consider the solid form of the materials and compatibility of any auxiliary used. This has culminated in the development of a two-step, one-jar protocol for heterocycle formation and
subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in
moderate to excellent yields
Translating solid state organic synthesis from a mixer mill to a continuous twin screw extruder
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 mâ3 dayâ1 in a mixer mill to 3395 kg mâ3 dayâ1 in a twin screw extruder
Controlling reactivity through liquid assisted grinding: the curious case of mechanochemical fluorination
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 3â:â1 ratio of monofluorinatedâ:âdifluorinated product was observed. Whereas, addition of 0.125 mL of acetonitrile (âź10% of the total volume of materials present) to the ground reaction mixture afforded 50â:â1 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
A continuous flow-batch hybrid reactor for commodity chemical synthesis enabled by inline NMR and temperature monitoring
Inline, real time NMR and temperature measurements have been used to optimise the continuous flow synthesis of difluoromethyltrimethylsilane (TMSCF2H) by the reduction of the Ruppert-Prakash reagent (TMSCF3). These measurements were used to maximise the space-time-yield, while ensuring this exothermic process remains safe. In this way, a three-fold increase in space-time-yield was achieved compared to the reported batch procedure, isolating 25âŻg of pure TMSCF2H after 105âŻmin
Exploring Multistep Continuous-Flow Hydrosilylation Reactions Catalyzed by Tris(pentafluorophenyl) borane
Exploring the combination of continuous-flow processes
with the boron Lewis acid catalyzed hydrosilylation of aldehydes and
ketones has delivered a robust and generally applicable reaction
protocol. Notably this approach permits ready access to high
temperatures and pressures and thus allows improved reactivity of
substrates that were previously recalcitrant under the traditional
approach. Efforts to quench the output from the flow reactor with water
showed surprising tolerance leading to the application of continuousflow systems in a multistep imine formation/hydrosilylation processes
to generate the corresponding secondary amines from their aldehyde
and aniline precursors
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