A reactivity-selectivity study of the Friedel-Crafts acetylation of 3,3′-dimethylbiphenyl and the oxidation of the acetyl derivatives

<p>Abstract</p> <p>Background</p> <p>Friedel-Crafts acetylation is an important route to aromatic ketones, in research laboratories and in industry. The acetyl derivatives of 3,3′-dimethylbiphenyl (3,3′-dmbp) have applications in the field of liquid crystals and polymers and may be oxidized to the dicarboxylic acids and derivatives that are of interest in cancer treatment.</p> <p>Findings</p> <p>The effect of solvent and temperature on the selectivity of monoacetylation of 3,3’-dmbp by the Perrier addition procedure was studied using stoichiometric amounts of reagents. 4-Ac-3,3′-dmbp was formed almost quantitatively in boiling 1,2-dichloroethane and this is almost twice the yield hitherto reported. Using instead a molar ratio of substrate:AcCl:AlCl₃ equal to 1:4:4 or 1:6:6 in boiling 1,2-dichloroethane, acetylation afforded 4,4′- and 4,6′-diacetyl-3,3′-dmbp in a total yield close to 100%. The acetyl derivatives were subsequently converted to the carboxylic acids by hypochlorite oxidation. The relative stabilities of the isomeric products and the corresponding σ-complexes were studied by DFT calculations and the data indicated that mono- and diacetylation followed different mechanisms.</p> <p>Conclusions</p> <p>Friedel-Crafts acetylation of 3,3′-dmbp using the Perrier addition procedure in boiling 1,2-dichloroethane was found to be superior to other recipes. The discrimination against the 6-acetyl derivative during monoacetylation seems to reflect a mechanism including an AcCl:AlCl₃ complex or larger agglomerates as the electrophile, whereas the less selective diacetylations of the deactivated 4-Ac-3,3′-dmbp are suggested to include the acetyl cation as the electrophile. The DFT data also showed that complexation of intermediates and products with AlCl₃ does not seem to be important in determining the mechanism.</p

A Modern View on the Red Sea Rift: Tectonics, Volcanism and Salt Blankets

Continental rifting and ocean basin formation can be observed at the present day in the Red Sea, which is used as the modern analogue for the formation of mid-ocean ridges. Competing theories for how spreading begins—either by quasi-instantaneous formation of a whole spreading segment or by initiation of spreading at multiple discrete “nodes” separated by thinned continental lithosphere—have been put forward based, until recently, on the observations that many seafloor features and geophysical anomalies (gravity, magnetics) along the axis of the Red Sea appeared anomalous compared to ancient and modern examples of ocean basins in other parts of the world. The latest research shows, however, that most of the differences between the Red Sea Rift (RSR) and other (ultra)slow-spreading mid-ocean ridges can be related to its relatively young age and the presence and movement of giant submarine salt flows that blanket large portions of the rift valley. In addition, the geophysical data that was previously used to support the presence of continental crust between the axial basins with outcropping oceanic crust (formerly named “spreading nodes”) can be equally well explained by processes related to the sedimentary blanketing and hydrothermal alteration. The observed spreading nodes are not separated from one another by tectonic boundaries but rather represent “windows” onto a continuous spreading axis which is locally inundated and masked by massive slumping of sediments or evaporites from the rift flanks. Volcanic and tectonic morphologies are comparable to those observed along slow and ultra-slow spreading ridges elsewhere and regional systematics of volcanic occurrences are related to variations in volcanic activity and mantle heat flow. Melt-salt interaction due to salt flows, that locally cover the active spreading segments, and the absence of large detachment faults as a result of the nearby Afar plume are unique features of the RSR. The differences and anomalies seen in the Red Sea still may be applicable to all young oceanic rifts, associated with plumes and/or evaporites, which makes the Red Sea a unique but highly relevant type example for the initiation of slow rifting and seafloor spreading and one of the most interesting targets for future ocean research

Aurora kinase inhibitors: Novel small molecules with promising activity in acute myeloid and Philadelphia-positive leukemias

Aurora kinases are a family of protein kinases that have a key role in multiple stages of mitosis. Over-expression of Aurora kinases, particularly Aurora A, has been demonstrated in a number of solid tumors and hematological malignancies. Not surprisingly, these serine/threonine kinases have become attractive small molecule targets for cancer therapeutics, with several inhibitors currently in early-phase clinical trials. A small number of compounds developed to date are highly selective for either Aurora A or Aurora B, while the majority inhibit both Aurora A and Aurora B; many of these compounds exhibit ‘off-target’ inhibition of kinases such as ABL, JAK2 and FLT3. It is currently unclear whether the therapeutic activity of these compounds in leukemia is primarily due to selective Aurora or multi-kinase inhibition. The most promising application for Aurora kinase inhibitors to date appears to be in FLT3-mutated acute myeloid leukemia (AML) and imatinib-resistant chronic myeloid leukemia/Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia, particularly when caused by the T315I mutation. Here we review the growing body of evidence supporting the use of Aurora kinase inhibitors as effective agents for AML and Ph+ leukemias