Vilsmeier-Haack reactions of 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans toward the synthesis of highly substituted pyridin-2(1H)-ones

A facile and efficient one-pot synthesis of highly substituted pyridin-2(IH)-ones was developed via Vilsmeier-Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.

One-pot synthesis of substituted isothiazol-3(2H)-ones: Intramolecular annulation of alpha-carbamoyl ketene-S,S-acetals via PIFA-Mediated N-S bond formation

A facile and efficient synthetic route towards; highly substituted isothiazol-3(2H)-ones 2 from readily available U.-carbamoyl ketene-S,S-acetals 1 is presented. The key step features the formation of an N-acylnitrenium ion, generated from the oxidization of substituted amides with the hypervalent iodine reagent phenyliodine(III) bis(trifluoroacetate) (PIFA), and its succeeding intramolecular amidation to form a new N-S bond affording the title compounds.

Structural and biological investigation of ferrocene-substituted 3-methylidene-1,3-dihydro-2H-indol-2-ones

The Knoevenagel condensation of 1,3-dihydro-2H-indol-2-one with ferrocene carboxaldehyde afforded an approximate 2:1 mixture of the geometrical isomers (E)- and (Z)-3-ferrocenylmethylidene-1,3-dihydro-2H-indol-2-one respectively in an overall 67% yield; the air and solution-stable isomers were readily separated by preparative thin layer chromatography and their structures were unequivocally elucidated in solution, by (1)H NMR spectroscopy, and in the solid phase, by X-ray crystallography; both isomers of displayed in vitro toxicity against B16 melanoma and Vero cell lines in the micromolar range and inhibited the kinase VEGFR-2 with IC(50) values of ca. 200 nM.

Seven 3-methylidene-1H-indol-2(3H)-ones related to the multiple-receptor tyrosine kinase inhibitor sunitinib

The solid-state structures of a series of seven substituted 3-methylidene-1H-indol-2(3H)-one derivatives have been determined by single-crystal X-ray diffraction and are compared in detail. Six of the structures {(3Z)-3-(1H-pyrrol-2- ylmethylidene)-1H-indol-2(3H)-one, C13H10N2O, (2a); (3Z)-3-( 2-thienylmethylidene)-1H-indol-2(3H)-one, C13H9NOS, (2b); (3E)-3-(2-furylmethylidene)-1H-indol-2(3H)-one monohydrate, C13H9NO2 center dot H2O, (3a); 3-(1-methylethylidene)-1H-indol- 2(3H)-one, C11H11NO, (4a); 3-cyclohexylidene-1H-indol- 2(3H)-one, C14H15NO, (4c); and spiro[1,3-dioxane-2,3'-indolin]- 2'-one, C11H11NO3, (5)} display, as expected, intermolecular hydrogen bonding (N-H center dot center dot center dot O=C) between the 1H-indol-2(3H)-one units. However, methyl 3-(1-methylethylidene)- 2-oxo-2,3-dihydro-1H-indole-1-carboxylate, C13H13NO3, (4b), a carbamate analogue of (4a) lacking an N-H bond, displays no intermolecular hydrogen bonding. The structure of (4a) contains three molecules in the asymmetric unit, while (4b) and (4c) both contain two independent molecules.

The Death Cults of prehistoric Malta:Mysteries of the Ancient Ones

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On Cherry-Picking ... or Trying to Have One’s Cake and Eating It: past principles and practice in the pursuit of an alternative to [full] EU membership

With the United Kingdom’s continued membership of the EU being increasingly questioned and the Prime Minister, David Cameron, committed to 're-negotiate’ the terms of membership, consideration is being given to what forms alternatives to [full] membership may take. While much current discussion focuses on the advantages and disadvantages of particular existing arrangements (e.g. European Economic Area, Swiss bilateralism), this paper examines the broader principles and practices that have to date underpinned – and undermined – EU’s attempts to develop alternatives to [full] EU membership. Drawing on an analysis of the evolution of association as an alternative to membership, the paper assesses the principled, practical and political limitations the EU faces – and imposes on itself – in offering an acceptable balance of rights and obligations to states not wishing to assume the mantle of full membership. In its assessment the paper considers various proposed models of affiliate and associate membership. It also situates consideration of the UK case in the broader context of the EU’s relations with other European non-member states for which membership may not be achievable and for which alternatives to membership (e.g. a form of privileged partnership) have been proposed. In doing so, the paper reflects on the precedent-setting consequences of any arrangement that the EU might reach with any state re-negotiating membership or withdrawing.

The ones that come ready made:The identification and use of Sus tusks as tools at prehistoric cave sites in Malaysia

Evidence for osseous technologies has featured in excavation reports from Southeast Asia for almost a century and from archaeological deposits as old as 43,000 years BP. However, in contrast to the significance that is placed on this technology in other parts of the world, until recently, Southeast Asian assemblages have drawn only very limited attention. Concentrating on evidence from Malaysia, the current paper examines one element of this inventory of tools: the deliberate modification of pig canines and the means by which such alteration can be distinguished from patterns of natural tooth wear. Particular attention is paid to the bearded pig (Sus barbatus), as it is one of the two species of wild boar in Malaysia whose tusks are most likely to have been used by prehistoric toolmakers. Reference is also made to wider, regional ethnographic examples of known tusk implements and their accredited uses to further assist in the identification process. Distinguishing criteria for worked tusk are formulated according to the type and extent of modification. These criteria are then applied to archaeological specimens recovered from two prehistoric cave sites in Malaysia, Gua Bintong and Niah Cave.