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 ( similar to 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.
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.
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.
IMPORTANCE: Prone positioning may improve outcomes in patients with severe acute respiratory distress syndrome (ARDS), but it is unknown whether prone positioning improves clinical outcomes among ...patients with ARDS who are undergoing venovenous extracorporeal membrane oxygenation (VV-ECMO) compared with supine positioning. OBJECTIVE: To test whether prone positioning vs supine positioning decreases the time to successful ECMO weaning in patients with severe ARDS supported by VV-ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients with severe ARDS undergoing VV-ECMO for less than 48 hours at 14 intensive care units (ICUs) in France between March 3, 2021, and December 7, 2021. INTERVENTIONS: Patients were randomized 1:1 to prone positioning (at least 4 sessions of 16 hours) (n = 86) or to supine positioning (n = 84). MAIN OUTCOMES AND MEASURES: The primary outcome was time to successful ECMO weaning within 60 days following randomization. Secondary outcomes included ECMO and mechanical ventilation–free days, ICU and hospital length of stay, skin pressure injury, serious adverse events, and all-cause mortality at 90-day follow-up. RESULTS: Among 170 randomized patients (median age, 51 IQR, 43-59 years; n = 60 women 35%), median respiratory system compliance was 15.0 (IQR, 10.7-20.6) mL/cm H2O; 159 patients (94%) had COVID-19–related ARDS; and 164 (96%) were in prone position before ECMO initiation. Within 60 days of enrollment, 38 of 86 patients (44%) had successful ECMO weaning in the prone ECMO group compared with 37 of 84 (44%) in the supine ECMO group (risk difference, 0.1% 95% CI, −14.9% to 15.2%; subdistribution hazard ratio, 1.11 95% CI, 0.71-1.75; P = .64). Within 90 days, no significant difference was observed in ECMO duration (28 vs 32 days; difference, −4.9 95% CI, −11.2 to 1.5 days; P = .13), ICU length of stay, or 90-day mortality (51% vs 48%; risk difference, 3.5% 95% CI, −12.7% to 19.7%; P = .62). No serious adverse events were reported during the prone position procedure. CONCLUSIONS AND RELEVANCE: Among patients with severe ARDS supported by VV-ECMO, prone positioning compared with supine positioning did not significantly reduce time to successful weaning of ECMO. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04607551
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