Potassium hydride behaves uniquely and differently than sodium hydride toward aryl halides. Its reactions with a range of haloarenes, including designed 2,6-dialkylhaloarenes, were studied in THF and ...in benzene. In THF, evidence supports concerted nucleophilic aromatic substitution, CSNAr, and the mechanism originally proposed by Pierre et al. is now validated through DFT studies. In benzene, besides this pathway, strong evidence for single electron transfer chemistry is reported. Experimental observations and DFT studies lead us to propose organic super electron donor generation to initiate BHAS (base-promoted homolytic aromatic substitution) cycles. Organic donor formation originates from deprotonation of benzene by KH; attack on benzene by the resulting phenylpotassium generates phenylcyclohexadienylpotassium that can undergo (i) deprotonation to form an organic super electron donor or (ii) hydride loss to afford biphenyl. Until now, BHAS reactions have been triggered by reaction of a base, MOtBu (M = K, Na), with many different types of organic additive, all containing heteroatoms (N or O or S) that enhance their acidity and place them within range of MOtBu as a base. This paper shows that with the stronger base, KH, even a hydrocarbon (benzene) can be converted into an electron-donating initiator.
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IJS, KILJ, NUK, PNG, UL, UM
Recent studies by Stoltz, Grubbs et al. have shown that triethylsilane and potassium tert‐butoxide react to form a highly attractive and versatile system that shows (reversible) silylation of arenes ...and heteroarenes as well as reductive cleavage of C−O bonds in aryl ethers and C−S bonds in aryl thioethers. Their extensive mechanistic studies indicate a complex network of reactions with a number of possible intermediates and mechanisms, but their reactions likely feature silyl radicals undergoing addition reactions and SH2 reactions. This paper focuses on the same system, but through computational and experimental studies, reports complementary facets of its chemistry based on a) single‐electron transfer (SET), and b) hydride delivery reactions to arenes.
Transfers: Triethylsilane and potassium tert‐butoxide react to form a highly attractive and versatile system. The work herein highlights the reductive transformations which lead to 1) C−N bond cleavage in N‐benzyl‐ and N‐allylindoles and 2) reduction of polycyclic arenes to their dihydro derivatives.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Socialism Allison, Mark
Victorian literature and culture,
01/2023, Volume:
51, Issue:
3
Journal Article
Peer reviewed
Open access
Anglo-American socialism has reached a curious impasse. Levels of economic inequality not seen since the nineteenth century would lead one to anticipate an upsurge in socialist affiliation and ...activism. Nevertheless, socialism has stagnated as a political force. This essay argues that, as a collectivist ideology, socialism demands a degree of communal identification that modern individuals find uncomfortable, even threatening, to the integrity of the self. Investigating this discomfort leads me to argue that, while socialism is not a religion (pace the claim of Gareth Stedman Jones), it nonetheless flourishes in eras of spiritual and societal foment. In such periods, communal effervescence softens the boundaries of the self, rendering collectivist ideologies like socialism more intuitive and appealing. Given desacralizing trends in Anglo-America, a contemporary socialist revival would seem unlikely. Consequently, I argue that it is time for progressives to embrace, rather than critique, the strong sense of individual autonomy and deep subjectivity that characterizes bourgeois individualism. The Victorian socialist canon provides many resources for a reconciliation of individualism and collectivism, which I illustrate via reference to H. G. Wells, John Stuart Mill, and Oscar Wilde.
This essay utilizes the publication of the first scholarly edition of The French Revolution: A History (1837) as an occasion to reassess this thoroughgoingly radical—and puzzlingly ...neglected—masterpiece. It explores how Thomas Carlyle's maverick conceptions of sympathy and affect, the relationship of the individual and the collective, and narrative itself underlie the audacious stylistic innovations that characterize this singular text. Moreover, this paper interprets Carlyle's history as a chronicle of inverted utopianism; that is, an apocalyptic manifestation of what is nevertheless a properly utopian longing for heaven on earth. Thus read, The French Revolution offers perspective on our own volatile times as well as a promise—or perhaps a warning—that the insurrectionary struggle for Liberty, Equality, and Fraternity is not over.
Education plays a pivotal role in establishing the elite status of a profession. This article sets out to understand the role of social and political influences in the determination of entry routes ...to professional accounting training with the Institute of Chartered Accountants of Scotland (ICAS). The article charts the development of various entry routes which converted ICAS from an Institute with few graduate entrants in the mid-1950s to an Institute with almost 100 per cent graduate entrants today.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
N-Arylindoles are transformed into dihydroacridines in a new type of rearrangement, through heating with triethylsilane and potassium tert-butoxide. Studies indicate that the pathway involves (i) the ...formation of indole radical anions followed by fragmentation of the indole C2–N bond, and (ii) a ring-closing reaction that follows a potassium-ion dependent hydrogen atom transfer step. Unexpected behaviors of ‘radical-trap’ substrates prove very helpful in framing the proposed mechanism.
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IJS, KILJ, NUK, UL, UM, UPUK
Abstract Purpose The International Conference on Harmonisation E14 guideline mandates an intensive cardiac safety evaluation in a clinical thorough QT study, typically in healthy subjects, for all ...new non-antiarrhythmic drugs with systemic bioavailability. This thorough QT study investigated the effects of therapeutic (2 mg) and supratherapeutic (10 mg) doses of siponimod (BAF312) on cardiac repolarization in healthy subjects. Methods The study was a randomized, double-blind, parallel-group, placebo- and moxifloxacin-controlled, multiple oral dose study. Eligible subjects were randomly assigned to 3 groups to receive siponimod (up-titration to 2 and 10 mg over 18 days), placebo (Days −1 to 18), or moxifloxacin 400 mg Days 10 and 18). Triplicate ECGs were extracted at prespecified time points from Holter ECGs recorded from 1 hour predose until 24 hours postdose at baseline and on-treatment assessment Days 10 and 18. The primary pharmacodynamic variable was the time-matched, placebo-corrected, baseline-adjusted mean QTcF (ΔΔQTcF) at steady-state conditions. In addition, the pharmacokinetic parameters of siponimod and its main circulating metabolite M3 and its metabolite M5 were evaluated. Findings Of the 304 enrolled subjects, 281 (92.4%) were included in the pharmacodynamic analysis and 270 (88.8%) completed the study. The upper bounds of the 2-sided 90% confidence intervals (CIs) for ΔΔQTcF at both siponimod doses were within the regulatory threshold of 10 milliseconds (ms) at all predefined on-treatment time points, with the absence of any dose-related effects. The highest observed upper limits of the 2-sided 90% CIs of 9.8 and 9.6 ms for therapeutic and supratherapeutic doses, respectively, were both observed at 3 hours postdose. No treatment-emergent QTc values >480 ms and no QTc increases of >60 ms from baseline were observed. Similar results were obtained with individualized heart rate correction of cardiac repolarization (QTcI). Assay validity was demonstrated by maximum ΔΔQTcF of >5 ms after 400 mg moxifloxacin on both on-treatment assessment days. The selected supratherapeutic dose produced approximately 5-fold higher exposures (Cmax and AUC) than the therapeutic dose, and was considered appropriate to investigate the effects of siponimod on QT/QTc at substantial multiples of the anticipated maximum therapeutic exposure. Implications The findings provide evidence that siponimod is not associated with a significant arrhythmogenic potential related to QT prolongation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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