George W. Weaver

Radical reactions with 3H-quinazolin-4-ones: synthesis of deoxyvasicinone, mackinazolinone, luotonin A, rutaecarpine and tryptanthrin

Alkyl, aryl, heteroaryl and acyl radicals have been cyclised onto the 2-position of 3H-quinazolin-4-one. The side chains containing the radical precursors were attached to the nitrogen atom in the 3-position. The cyclisations take place by aromatic homolytic substitution hence retain the aromaticity of the 3H-quinazolin-4-one ring. The highest yields were obtained using hexamethylditin to facilitate cyclisation rather than reduction without cyclisation. The alkaloids deoxyvasicinone , mackinazolinone , tryptanthrin , luotonin A and rutaecarpine were synthesised by radical cyclisation onto 3H-quinazolin-4-one.

Facile One‐Pot Synthesis of 4‐Hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic Acid 1,1‐Dioxide

Abstract We report a convenient synthesis of 4‐hydroxy‐2‐methyl‐(2H)‐1,2‐benzothiazine‐3‐sulfonic acid‐1,1‐dioxide (6a) prepared in a novel one‐pot reaction. The synthesis involves two transformations starting from 2‐methyl‐2H‐1,2‐benzothiazin‐4‐(3H)‐one 1,1‐dioxide (7) with an overall yield better than that from the stepwise process, as well as the alternate procedure starting from saccharin (1). One‐pot synthesis of an important intermediate, saccharin‐N‐methane sulfonic acid (4), is also described.

Structure and properties of TentaGel resin beads: implications for combinatorial library chemistry.

SummaryIn view of the widespread use of TentaGel resin beads for the synthesis of combinatorial libraries, the properties of TentaGel resin have been examined using a combination of confocal laser microscopy and NMR spectroscopy. Evidence is presented that trypsin, a 23.5-kDa enzyme, can penetrate to the core of 90-μm TentaGel beads, and that the matrix of such beads permits molecular motion at a similar rate to that in solution. The beads act as a separate gel phase rather than as a porous solid. These conclusions have important implications for the bioassay of on-bead combinatorial chemical libraries.

Synthesis of fluorinated fused benzofurans and benzothiophenes: Smiles-type rearrangement and cyclisation of perfluoro(het)aryl ethers and sulfides

Lithium-bromine exchange in 2-bromophenyl perfluoroaryl ethers or sulfides affords fused fluorinated benzofurans or benzothiophenes respectively by S(N)Ar substitution of the adjacent fluorine in the perfluoroaryl substituent. The structures of the new compounds were confirmed by NMR spectroscopy and single crystal X-ray diffraction analysis. In the case of 2-bromophenyl tetrafluoropyrid-4-yl ether, lithiation promoted a Smiles-type rearrangement which led to formation of 4-(2-hydroxyphenyl)tetrafluoropyridine, for which the structure was confirmed by X-ray crystallography.

Synthesis, Characterization and Antibacterial Activity of Azomethine Derivatives Derived from 2-Formylphenoxyacetic Acid

A series of eight new azomethine derivatives were synthesized by reacting 2-formylphenoxyacetic acid with aromatic amines. The chemical structures of these compounds were confirmed by means of 1H-NMR, 13C-NMR, MS and elemental analysis. The compounds were assayed by the disc diffusion method for antibacterial against Staphylococcus aureus and Escherichia coli. Among the compounds tested, 2a, 2b, 2e, 2g and 2h exhibited good antibacterial activity, almost equal to that of Ciprofloxacin used as standard.

Synthesis of 2-aryl-2H-indazoles by base catalysed reaction of 2-nitrobenzyl triphenylphosphonium bromide and aryl isocyanates

Abstract The synthesis of a series of 2-aryl-2 H -indazoles is reported. These compounds are obtained in moderate to good yield by reaction of 2-nitrobenzyl triphenylphosphonium bromide with aryl isocyanates, catalysed by sodium hydride or DBU.

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

Additive manufacturing or ‘3D printing’ is being developed as a novel manufacturing process for the production of bespoke micro- and milliscale fluidic devices. When coupled with online monitoring and optimisation software, this offers an advanced, customised method for performing automated chemical synthesis. This paper reports the use of two additive manufacturing processes, stereolithography and selective laser melting, to create multifunctional fluidic devices with embedded reaction monitoring capability. The selectively laser melted parts are the first published examples of multifunctional 3D printed metal fluidic devices. These devices allow high temperature and pressure chemistry to be performed in solvent systems destructive to the majority of devices manufactured via stereolithography, polymer jetting and fused deposition modelling processes previously utilised for this application. These devices were integrated with commercially available flow chemistry, chromatographic and spectroscopic analysis equipment, allowing automated online and inline optimisation of the reaction medium. This set-up allowed the optimisation of two reactions, a ketone functional group interconversion and a fused polycyclic heterocycle formation, via spectroscopic and chromatographic analysis.

Synthesis of 2-aryl-imidazo[4,5-d][1,2,3]triazoles from a 4-nitro-imidazol-5-yl phosphoramidate and aryl isocyanates

Abstract The synthesis of a series of 2-aryl-2 H ,4 H -imidazo[4,5- d ][1,2,3]triazoles is reported. These compounds are obtained in moderate to good yield by reaction of triethyl N -1-ethyl-2-methyl-4-nitro-1 H -imidazol-5-yl phosphoramidate with aryl isocyanates.

SYNTHESIS OF BIS(GLYCOALDEHYDE) PHOSPHODIESTER AND MIXED GLYCOALDEHYDE-TRIOSE PHOSPHODIESTERS

Abstract The syntheses of the potentially prebiotic compounds, bis(glycoaldehyde) phosphodiester 1, dihydroxyacetonephosphoglycoaldehyde 2 and glyceraldehyde-2-phosphoglycoaldehyde 3 have been achieved.

Reactions of an imidazo[4,5-c]isoxazole-6-carboxylate with electron deficient acetylenes

Abstract The synthesis of the first examples of the imidazo[4,5-c]isoxazole ring system has recently been reported,2 but little is known about the chemistry of this heterocycle. In this paper we describe our investigation into the behaviour of an imidazo[4,5-c]isoxazole-6-carboxylate ester with acetylenic esters and ketones. A complex reaction sequence is found to occur, involving addition of two molecules of alkyne followed by ring opening and fragmentation, leading to the formation of 2-pyrrol-2-yl imidazoles in moderate yield. The mechanism and scope of the reaction is discussed.