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 ‘direct’ 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

\u27I\u27m not a druggie, I\u27m just a diabetic\u27: a qualitative study of stigma from the perspective of adults with type 1 diabetes

While health-related stigma has been the subject of considerable research in other conditions (eg, HIV/AIDS, obesity), it has not received substantial attention in diabetes. Our aim was to explore perceptions and experiences of diabetes-related stigma from the perspective of adults with type 1 diabetes mellitus (T1DM)

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 cross‐coupling reaction via mechanochemical methods is reported. The reported method exhibits a broad substrate scope for both C(sp3)–C(sp2) and C(sp2)–C(sp2) couplings and is tolerant to many important functional groups. The method may offer broad reaching opportunities for the in 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/alkyl–SCF2H 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 m−3 day−1 in a mixer mill to 3395 kg m−3 day−1 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 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

Associations between physical activity and depressive symptoms by weight status among adults with type 2 diabetes: Results from diabetes miles-Australia

© 2017 Human Kinetics, Inc. Background: To examine associations between physical activity (PA) and depressive symptoms among adults with type 2 diabetes mellitus (Type 2 DM), and whether associations varied according to weight status. Methods: Diabetes MILES-Australia is a national survey of adults with diabetes, focused on behavioral and psychosocial issues. Data from 705 respondents with Type 2 DM were analyzed, including: demographic and clinical characteristics, PA (IPAQ-SF), depressive symptoms (PHQ-9), and BMI (self-reported height and weight). Data analysis was performed using ANCOVA. Results: Respondents were aged 59 ± 8 years; 50% women. PA was negatively associated with depressive symptoms for the overall sample (?p 2= 0.04,P < .001) and all weight categories separately: healthy (?p 2 0.11 P = .041,), overweight (?p 2= 0.04, P = .025) and obese (?p 2 = 0.03, P = .007). For people who were healthy (BMI 18.5 to 24.9) or overweight (BMI 25 to 29.9), high amounts of PA were significantly associated with fewer depressive symptoms; for adults who were obese (BMI ? 30) however, both moderate and high amounts were associated with fewer depressive symptoms. Conclusions: PA is associated with fewer depressive symptoms among adults with Type 2DM, however the amount of PA associated with fewer depressive symptoms varies according to weight status. Lower amounts of PA might be required for people who are obese to achieve meaningful reductions in depressive symptoms compared with those who are healthy weight or overweight. Further research is needed to establish the direction of the relationship between PA and depressive symptoms