Co-reporter:Joseph L. Howard;Christiane Schotten
Reaction Chemistry & Engineering (2016-Present) 2017 vol. 2(Issue 3) pp:281-287
Publication Date(Web):2017/06/08
DOI:10.1039/C7RE00034K
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.
Co-reporter:Joseph L. Howard;Yerbol Sagatov;Laura Repusseau;Christiane Schotten
Green Chemistry (1999-Present) 2017 vol. 19(Issue 12) pp:2798-2802
Publication Date(Web):2017/06/19
DOI:10.1039/C6GC03139K
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.
Co-reporter:Joseph L. Howard, Christiane Schotten, Stephen T. Alston and Duncan L. Browne
Chemical Communications 2016 vol. 52(Issue 54) pp:8448-8451
Publication Date(Web):07 Jun 2016
DOI:10.1039/C6CC02693A
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.
Co-reporter:Jian-Siang Poh, Cristina García-Ruiz, Andrea Zúñiga, Francesca Meroni, David C. Blakemore, Duncan L. Browne and Steven V. Ley
Organic & Biomolecular Chemistry 2016 vol. 14(Issue 25) pp:5983-5991
Publication Date(Web):20 May 2016
DOI:10.1039/C6OB00970K
We report conditions for the preparation of a range of trifluoromethylated isoxazole building blocks through the cycloaddition reaction of trifluoromethyl nitrile oxide. It was found that controlling the rate (and therefore concentration) of the formation of the trifluoromethyl nitrile oxide was Critical for the preferential formation of the desired isoxazole products versus the furoxan dimer. Different conditions were optimised for both aryl- and alkyl-substituted alkynes. In addition, the reactivity at the isoxazole 4-position has been briefly explored for these building blocks. Conditions for intermolecular C–H arylation, lithiation and electrophile quench, and alkoxylation were all identified with brief substrate scoping that signifies useful tolerance to a range of functionalities. Finally, complementary processes for structural diversification through either intramolecular cyclisation or intermolecular cross-coupling were developed.
Co-reporter:Christiane Schotten, Dorota Plaza, Simone Manzini, Steven P. Nolan, Steven V. Ley, Duncan L. Browne, and Alexei Lapkin
ACS Sustainable Chemistry & Engineering 2015 Volume 3(Issue 7) pp:1453
Publication Date(Web):May 26, 2015
DOI:10.1021/acssuschemeng.5b00397
The direct chemical conversion of cocoa butter triglycerides, a material available as a postmanufacture waste stream from the food industry, to 1-decene by way of ethenolysis is reported. The conversion of the raw waste material was made possible by use of 1 mol % of the [RuCl2(iBu-phoban)2(3-phenylindenyl)] catalyst. The process has been investigated in both batch and flow conditions, where the latter approach employs a Teflon AF-2400 tube-in-tube gas–liquid membrane contactor to deliver ethylene to the reaction system. These preliminary studies culminate in a continuous processing system, which maintained a constant output over a 150 min period tested.Keywords: Flow chemistry; Food waste; Green chemistry; Metathesis; Triglycerides; Valorization
Co-reporter:Jian-Siang Poh, Cristina García-Ruiz, Andrea Zúñiga, Francesca Meroni, David C. Blakemore, Duncan L. Browne and Steven V. Ley
Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 25) pp:NaN5991-5991
Publication Date(Web):2016/05/20
DOI:10.1039/C6OB00970K
We report conditions for the preparation of a range of trifluoromethylated isoxazole building blocks through the cycloaddition reaction of trifluoromethyl nitrile oxide. It was found that controlling the rate (and therefore concentration) of the formation of the trifluoromethyl nitrile oxide was Critical for the preferential formation of the desired isoxazole products versus the furoxan dimer. Different conditions were optimised for both aryl- and alkyl-substituted alkynes. In addition, the reactivity at the isoxazole 4-position has been briefly explored for these building blocks. Conditions for intermolecular C–H arylation, lithiation and electrophile quench, and alkoxylation were all identified with brief substrate scoping that signifies useful tolerance to a range of functionalities. Finally, complementary processes for structural diversification through either intramolecular cyclisation or intermolecular cross-coupling were developed.
Co-reporter:Joseph L. Howard, Christiane Schotten, Stephen T. Alston and Duncan L. Browne
Chemical Communications 2016 - vol. 52(Issue 54) pp:NaN8451-8451
Publication Date(Web):2016/06/07
DOI:10.1039/C6CC02693A
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.