Daniel K. Whelligan

High performance aliphatic-heterocyclic benzyl-quaternary ammonium radiation-grafted anion-exchange membranes

Anion-exchange membranes (AEM) containing saturated-heterocyclic benzyl-quaternary ammonium (QA) groups synthesised by radiation-grafting onto poly(ethylene-co-tetrafluoroethylene) (ETFE) films are reported. The relative properties of these AEMs are compared with the benchmark radiation-grafted ETFE-g-poly(vinylbenzyltrimethylammonium) AEM. Two AEMs containing heterocyclic-QA head groups were down-selected with higher relative stabilities in aqueous KOH (1 mol dm−3) at 80 °C (compared to the benchmark): these 100 μm thick (fully hydrated) ETFE-g-poly(vinylbenzyl-N-methylpiperidinium)- and ETFE-g-poly(vinylbenzyl-N-methylpyrrolidinium)-based AEMs had as-synthesised ion-exchange capacities (IEC) of 1.64 and 1.66 mmol g−1, respectively, which reduced to 1.36 mmol dm−3 (ca. 17–18% loss of IEC) after alkali ageing (the benchmark AEM showed 30% loss of IEC under the same conditions). These down-selected AEMs exhibited as-synthesised Cl− ion conductivities of 49 and 52 mS cm−1, respectively, at 90 °C in a 95% relative humidity atmosphere, while the OH− forms exhibited conductivities of 138 and 159 mS cm−1, respectively, at 80 °C in a 95% relative humidity atmosphere. The ETFE-g-poly(vinylbenzyl-N-methylpyrrolidinium)-based AEM produced the highest performances when tested as catalyst coated membranes in H2/O2 alkaline polymer electrolyte fuel cells at 60 °C with PtRu/C anodes, Pt/C cathodes, and a polysulfone ionomer: the 100 μm thick variant (synthesised from 50 μm thick ETFE) yielded peak power densities of 800 and 630 mW cm−2 (with and without 0.1 MPa back pressurisation, respectively), while a 52 μm thick variant (synthesised from 25 μm thick ETFE) yielded 980 and 800 mW cm−2 under the same conditions. From these results, we make the recommendation that developers of AEMs, especially pendent benzyl-QA types, should consider the benzyl-N-methylpyrrolidinium head-group as an improvement to the current de facto benchmark benzyltrimethylammonium head-group.

An optimised synthesis of high performance radiation-grafted anion-exchange membranes

High performance benzyltrimethylammonium-type alkaline anion-exchange membranes (AEM), for application in electrochemical devices such as anion-exchange membrane fuel cells (AEMFC), were prepared by the radiation grafting (RG) of vinylbenzyl chloride (VBC) onto 25 μm thick poly(ethylene-co-tetrafluoroethylene) (ETFE) films followed by amination with trimethylamine. Reductions in the electron-beam absorbed dose and amount of expensive, potentially hazardous VBC were achieved by using water as a diluent (reduced to 30–40 kGy absorbed dose and 5 vol% VBC) instead of the prior state-of-the-art method that used organic propan-2-ol diluent (required 70 kGy dose and 20 vol% VBC monomer). Furthermore, the water from the aqueous grafting mixture was easily separated from the residual monomer (after cooling) and was reused for a further grafting reaction: the resulting AEM exhibited an ion-exchange capacity of 2.1 mmol g−1 (cf. 2.1 mmol g−1 for the AEM made using a fresh grafting mixture). The lower irradiation doses resulted in mechanically stronger RG-AEMs compared to the reference RG-AEM synthesised using the prior state-of-the-art method. A further positive off-shoot of the optimisation process was the discovery that using water as a diluent resulted in an enhanced (i.e. more uniform) distribution of VBC grafts as proven by Raman microscopy and corroborated using EDX analysis: this led to enhancement in the Cl− anion-conductivities (up to 68 mS cm−1 at 80 °C for the optimised fully hydrated RG-AEMs vs. 48 mS cm−1 for the prior state-of-the-art RG-AEM reference). A down-selected RG-AEM with an ion-exchange capacity = 2.0 mmol g−1, that was synthesised using the new greener protocol with a 30 kGy electron-beam absorbed dose, led to an exceptional beginning-of-life H2/O2 AEMFC peak power density of 1.16 W cm−2 at 60 °C in a benchmark test using industrial standard Pt-based electrocatalysts and unpressurised gas supplies: this was higher than the 0.91 W cm−1 obtained with the reference RG-AEM (IEC = 1.8 mmol g−1) synthesised using the prior state-of-the-art protocol.

Aminopyrazine Inhibitors Binding to an Unusual Inactive Conformation of the Mitotic Kinase Nek2: Sar and Structural Characterization.

We report herein the first systematic exploration of inhibitors of the mitotic kinase Nek2. Starting from HTS hit aminopyrazine 2, compounds with improved activity were identified using structure-based design. Our structural biology investigations reveal two notable observations. First, 2 and related compounds bind to an unusual, inactive conformation of the kinase which to the best of our knowledge has not been reported for other types of kinase inhibitors. Second, a phenylalanine residue at the center of the ATP pocket strongly affects the ability of the inhibitor to bind to the protein. The implications of these observations are discussed, and the work described here defines key features for potent and selective Nek2 inhibition, which will aid the identification of more advanced inhibitors of Nek2.

Two-Step Synthesis of Aza- and Diazaindoles from Chloroamino-N-heterocycles Using Ethoxyvinylborolane

An efficient two-step route to a broad range of aza- and diazaindoles was established, starting from chloroamino-N-heterocycles, without the need for protecting groups. The method involves an optimized Suzuki-Miyaura coupling with (2-ethoxyvinyl)borolane followed by acetic acid-catalyzed cyclization.

Silenes as novel synthetic reagents: identification of a practical method for silene generation and trapping

The elucidation of a robust and reliable sequence for the generation of highly reactive transient silenes from simple aldehydes is described. The key step involves a silyl-modified Peterson olefination which critically depends on the presence of a sub-stoichiometric amount of soluble lithium salts (LiBr).

Non-fluorinated pre-irradiation-grafted (peroxidated) LDPE-based anion-exchange membranes with high performance and stability

Radiation-grafted anion-exchange membrane (RG-AEM) research has predominantly focused on the chemical stability of the polymer-bound positively-charged head-groups that enable anion conduction. The effect of the backbone polymer chemistry, of the precursor film, on RG-AEM stability has been studied to a lesser extent and not for RG-AEMs made from pre-irradiation grafting of polymer films in air (peroxidation). The mechanical strength of polymer films is generally weakened by exposure to high radiation doses (e.g. from a high-energy e−-beam) and this is mediated by chemical degradation of the main chains: fluorinated films mechanically weaken at lower absorbed doses compared to non-fluorinated films. This study systematically compares the performance difference between RG-AEMs synthesised from a non-fluorinated polymer film (low-density polyethylene – LDPE) and a partially-fluorinated polymer film (poly(ethylene-co-tetrafluoroethylene) – ETFE) using the peroxidation method (pre-irradiation in air using an e−-beam). Both the LDPE and ETFE precursor films used were 25 μm in thickness, which led to RG-AEMs of hydrated thicknesses in the range 52–60 μm. The RG-AEMs (designated LDPE-AEM and ETFE-AEM, respectively) all contained identical covalently-bound benzyltrimethylammonium (BTMA) cationic head-groups. An LDPE-AEM achieved a OH− anion conductivity of 145 mS cm−1 at 80 °C in a 95% relative humidity environment and a Cl− anion conductivity of 76 mS cm−1 at 80 °C when fully hydrated. Alkali stability testing showed that the LDPE-AEM mechanically weakened to a much lower extent when treated in aqueous alkaline solution compared to the ETFE-AEM. This LDPE-AEM outperformed the ETFE-AEM in H2/O2 anion-exchange membrane fuel cell (AEMFC) tests due to high anion conductivity and enhanced in situ water transport (due to the lower density of the LDPE precursor): a maximum power density of 1.45 W cm−2 at 80 °C was achieved with an LDPE-AEM alongside a Pt-based anode and cathode (cf. 1.21 mW cm−2 for the benchmark ETFE-AEM). The development of more mechanically robust RG-AEMs has, for the first time, led to the ability to routinely test them in fuel cells at 80 °C (cf. 60 °C was the prior maximum temperature that could be routinely used with ETFE-based RG-AEMs). This development facilitates the application of non-Pt catalysts: 931 mW cm−2 was obtained with the use of a Ag/C cathode at 80 °C and a Ag loading of 0.8 mg cm−2 (only 711 mW cm−2 was obtained at 60 °C). This first report on the synthesis of large batch size LDPE-based RG-AEMs, using the commercially amenable peroxidation-type radiation-grafting process, concludes that the resulting LDPE-AEMs are superior to ETFE-AEMs (for the intended applications).

The synthesis of pseudo-geminal, pseudo-ortho and Ortho hydroxy-oxazolinyl[2.2]paracyclophanes for use as ligands in asymmetric catalysis

Synthetic routes to pseudo-geminal, pseudo-ortho and ortho hydroxy-oxazolinyl-[2.2]paracyclophanes (and the diastereoisomers of each) for use as N,O ligands in asymmetric catalysis have been devised. The substitution pattern was found to have a strong effect on the rate and enantioselectivity of the formed catalyst in the addition of diethylzinc to benzaldehyde.

Hypervalent iodine(III)-mediated oxidative acetoxylation of 2-methoxyphenols for regiocontrolled nitrogen benzannulation

Abstract Nitrogen-tethered 2-methoxyphenols are conveniently dearomatized into synthetically useful orthoquinol acetates by treatment with phenyliodine(III) diacetate in methylene chloride at low temperature. Subsequent fluoride- or base-induced intramolecular nucleophilic addition reactions furnish indole and quinoline derivatives. The potential of this methodology for the synthesis of a functionalized lycorine-type alkaloid skeleton is introduced here.

Synthesis of amino-substituted indoles using the Bartoli reaction

We report herein the concise preparation of a range of functionalised aminoindoles via a new application of the Bartoli reaction. Scope and limitations of the methodology have been extensively studied to reveal the importance of protecting groups and substitution patterns. The use of amino substituted nitroanilines for the Bartoli reaction is to our knowledge unprecedented. Our work thus represents a novel entry into substituted aminoindoles which are relevant building blocks for both the fine chemical and pharmaceutical industry.

Radiation-induced grafting of a butyl-spacer styrenic monomer onto ETFE: the synthesis of the most alkali stable radiation-grafted anion-exchange membrane to date

An ETFE-(poly(ethylene-co-tetrafluoroethylene))-based radiation-grafted anion-exchange membrane (AEM) containing a butyl-spacer between the benzene and the methylpyrrolidinium groups (C4-AEM) had double the ex situ alkali stability at 80 °C compared to a methylene benchmark (C1-AEM). H2/O2 fuel cells containing C4-AEM still achieved a peak power density of >1 W cm−2.