Declining Use of the Hallervorden-Spatz Disease Eponym in the Last Two Decades

There has been a movement to rename Hallervorden-Spatz disease to pantothenate kinase-associated neurodegeneration given Hallervorden and Spatz's complicity in murderous Nazi programs. Similar controversy surrounds Reiter syndrome, and 2 studies demonstrated decreased unqualified use of that eponym in the literature, but not in textbooks. There have been no similar studies regarding Hallervorden-Spatz disease. The authors performed a MEDLINE search (1990-2010) looking for unqualified use of Hallervorden-Spatz disease and performed statistical analysis. They defined "unqualified" as having no reference to the eponym's disfavored use. They then looked in 6 neurology textbooks. The authors identified 156 of 278 articles (56.1%) containing unqualified use of Hallervorden-Spatz disease. But there was a declining trend (P = .000), with 70/80 (87.5%) of articles from 1990 to 1999 and 86/198 (43.4%) from 2000 to 2010. There was also decreased unqualified use of the eponyms in textbooks, with all recent editions using pantothenate kinase-associated neurodegeneration instead. The significant decrease in unqualified use of Hallervorden-Spatz disease is reassuring

Synthesis of Quinoline-Based NNN-Pincer Nickel(II) Complexes: A Robust and Improved Catalyst System for C–H Bond Alkylation of Azoles with Alkyl Halides

The quinoline-based pincer nickel­(II) complexes κ^N<i>,κ</i>^N<i>,κ</i>^N-{R₂N-C₆H₄-(μ-N)-C₉H₆N}­NiX ((^R2NNN^Q)­NiCl: R = Me, <b>2a</b>; R = Et, <b>2b</b>) were synthesized by the reaction of the ligand precursors (^R2NNN^Q)H (R = Me, <b>1a</b>; R = Et, <b>1b</b>) with (DME)­NiCl₂ in the presence of Et₃N. Similarly, the pincer nickel­(II) derivatives (^R2NNN^Q)­NiX (R = Me, X = Br, <b>3a</b>; R = Et, X = Br, <b>3b</b>; R = Me, X = OAc, <b>4a</b>) were obtained by treatment of the ligands (^R2NNN^Q)H with the nickel precursor (THF)₂NiBr₂ or Ni­(OAc)₂. All of these complexes were characterized by ¹H and ¹³C NMR spectroscopy as well as by elemental analysis. Further, the molecular structures of <b>2a</b> and <b>3a</b>,<b>b</b> were elucidated by X-ray crystallography. Complex <b>2a</b> is found to be an efficient catalyst for the direct C–H bond alkylation of substituted benzothiazoles and oxazoles with various unactivated alkyl halides containing β-hydrogens under mild reaction conditions. The catalyst <b>2a</b> is very robust and was recycled and reused five times for the alkylation reaction without a decrease in its catalytic activity. Preliminary studies reveal that the catalyst <b>2a</b> acts as an active catalyst and the alkylation reaction appears to operate via a radical pathway

Mechanistic Aspects of Pincer Nickel(II)-Catalyzed C–H Bond Alkylation of Azoles with Alkyl Halides

The quinolinyl-based pincer nickel complex, κ^N,κ^N,κ^N-{C₉H₆N-(μ-N)-C₆H₄–NMe₂}­NiCl [(^QNNN^Me2)­NiCl; (<b>1</b>)] has recently been demonstrated to be an efficient and robust catalyst for the alkylation of azoles with alkyl halides under copper-free conditions. Herein, we report the detailed mechanistic investigation for the alkylation of azoles catalyzed by (^QNNN^Me2)­NiCl (<b>1</b>), which highlights an iodine-atom transfer (IAT) mechanism for the reaction involving a Ni^II/Ni^III process. Deuterium labeling experiments indicate reversible cleavage of the benzothiazole C–H bond, and kinetic studies underline a fractional negative rate order with the substrate benzothiazole. The involvement of an alkyl radical during the alkylation is validated by radical clock and external additive experiments. An active intermediate species (^QNNN^Me2)­Ni­(benzothiazolyl) (<b>5a</b>) has been isolated and structurally characterized. The complex (^QNNN^Me2)­Ni­(benzothiazolyl) (<b>5a</b>) is found to be the resting state of catalyst <b>1</b>. Kinetic analysis of electronically different intermediates suggests that the step involving the reaction of <b>5a</b> with alkyl iodide is crucial and a rate-influencing step. DFT calculations strongly support the experimental findings and corroborate an IAT process for the alkylation reaction

Mechanistic Aspects of Pincer Nickel(II)-Catalyzed C–H Bond Alkylation of Azoles with Alkyl Halides

The quinolinyl-based pincer nickel complex, κ^N,κ^N,κ^N-{C₉H₆N-(μ-N)-C₆H₄–NMe₂}­NiCl [(^QNNN^Me2)­NiCl; (<b>1</b>)] has recently been demonstrated to be an efficient and robust catalyst for the alkylation of azoles with alkyl halides under copper-free conditions. Herein, we report the detailed mechanistic investigation for the alkylation of azoles catalyzed by (^QNNN^Me2)­NiCl (<b>1</b>), which highlights an iodine-atom transfer (IAT) mechanism for the reaction involving a Ni^II/Ni^III process. Deuterium labeling experiments indicate reversible cleavage of the benzothiazole C–H bond, and kinetic studies underline a fractional negative rate order with the substrate benzothiazole. The involvement of an alkyl radical during the alkylation is validated by radical clock and external additive experiments. An active intermediate species (^QNNN^Me2)­Ni­(benzothiazolyl) (<b>5a</b>) has been isolated and structurally characterized. The complex (^QNNN^Me2)­Ni­(benzothiazolyl) (<b>5a</b>) is found to be the resting state of catalyst <b>1</b>. Kinetic analysis of electronically different intermediates suggests that the step involving the reaction of <b>5a</b> with alkyl iodide is crucial and a rate-influencing step. DFT calculations strongly support the experimental findings and corroborate an IAT process for the alkylation reaction