George Tennant

Synthesis and application of a novel coupling reagent, ethyl 1-hydroxy-1H -1,2,3-triazole-4-carboxylate

Abstract An optimal coupling reagent, ethyl 1-hydroxy-1H-1,2,3-triazole-4-carboxylate (HOCt), has been designed and synthesised for application to solid phase peptide synthesis using Fmoc chemistry. It is used in combination with carbodiimide reagents, has very high coupling efficiency, and does not absorb at 302nm, thus allowing real-time monitoring of each coupling cycle. Its applications in the synthesis of endothelin analogues and difficult sequences are also discussed.

PHOTOPOLYMERISATION OF ION-SELECTIVE MEMBRANES ONTO SILICON NITRIDE SURFACES FOR ISFET FABRICATION

Abstract A silicon nitride surface has been chemically modified with an ion-sensitive membrane consisting of a styrene—vinylbenzo-[18]-crown-6 copolymer (monomer ratio 4:1). The ionophore is therefore covalently bound to the polystyrene backbone so as to prevent gradual loss to the analyte solution. Silylation of the Si3N4 surface with vinyltrimethoxysilane allows the polymer film itself to be attached to the substrate via chemical bonding by in situ copolymerisation with the surface vinyl groups. The method chosen is that of photoinitiated polymerisation through a mask to be used for ISFET fabrication at wafer stage. The response to potassium ions observed with a 0.1 μm thick membrane is 37 mV per pK+ unit between 10−3 and 10−1 mol dm−3.

Lewis acid catalysed cyclisation and halogen exchange reactions of 1,1′-biphenyl-2-yl isocyanide dihalides

1,1′-Biphenyl-2-yl isocyanide dichloride and dibromide undergo unprecedented intramolecular Friedel–Crafts type cyclisation reactions catalysed by various Lewis acids affording useful synthetic methods for otherwise difficult to access 6-chloro- and 6-bromo-phenanthridines; nucleophilic displacement reactions of the latter and halogen exchange reactions of 1,1′-biphenyl-2-yl isocyanide dichloride and dibromide are also described.

Trapping of dopant anions in two-layer polypyrrole films

A new method to decrease leaching out of dopant ions from conducting polypyrrole films using a two-layer system is presented.

Diazoalkylideneamine–1,2,3-triazole tautomerism in 1,2,3-triazolo[1,5-a]pyrimidines at elevated temperatures

Simple examples of diazoalkylideneamine–1,2,3-triazole equilibria have been demonstrated for the first time in a fused system by variable temperature 1H n.m.r. studies of a series of 1,2,3-triazolo[1,5-a]pyrimidines.

The chemistry of polyazaheterocyclic compounds. Part VIII. Coupling reactions of 1,2,4-triazole-5-diazonium nitrate with active methylene compounds. A new general route to [1,2,4]triazolo[5,1-c][1,2,4]triazine derivatives

1,2,4-Triazole-5-diazonium nitrate couples with a variety of active methylene compounds (diethyl malonate, ethyl benzoylacetate, acetylacetone, benzoylmacetone, dibenzoylmethane, and benzoylacetonitrile) at room temperature in the presence of sodium acetate of afford 1,2,4-triazol-5-ylhydrazones, which are smoothyl converted in warm aqueous ethanolic sodium acetate or glacial acetic acid, in high yield, into the corresponding [1,2,4]triazolo[5,1-c][1,2,4]triazine derivatives. In the cases of ethyl acetoacetate and cyanoacetamide the derived hydrazones were unstable and underwent spontaneous cyclisation even at room temperature, affording the corresponding triazolotriazines.

A new heterocyclisation reaction leading to cinnolin-4(1H)-one derivatives

2-Nitrophenacylidene phenylhydrazones (2) undergo base-catalysed cyclisation by intramolecular nucleophilic displacement of the nitro-group by the ortho-side-chain, providing an efficient general route to 3-substituted 1-phenylcinnolin-4(1H)-ones (3).

Synthesis of 5-substituted imidazo[4,5-b]pyridinones by annelation of 4-amino-5-ethoxalyl-1H-imidazole derivatives with active methylene compounds

A new synthetic route to imidazo[4,5-b]pyridinones with a range of substituents at the 6-position has been developed. These compounds can be prepared in four steps from readily available 5-chloro-4-nitroimidazoles. The key step involves construction of the pyridine ring by annelation of 4-amino-5-ethoxalylimidazoles with active methylene compounds under dehydrating conditions or by acylation with substituted acetyl chlorides followed by spontaneous cyclisation. An exception is the reaction in which cyclisation of a phenylacetyl derivative occurs to give a seven-membered ring, forming an imidazo[4,5-b]azepinedione.

Cyclisation reactions of azolylhydrazones derived from ethyl cyanoacetate and malononitrile. Formation of azolo[5,1-c][1,2,4]triazines

Ethyl 2-cyano-2-(1,2,4-trizol-5-ylhydrazono)acetate (2a) cyclised in aqueous ethanol to a mixture of ethyl 7-amino-1,2,4-triazolo[5,1-c][1,2,4]triazine-6-carboxylate (3a) and 4,7-dihydro-7-oxo-1,2,4-triazolo[5,1-c]-[1,2,4]triazine-6-carbonitrile (4a); in acetic acid the product was mainly the amino-ester (3a) whereas in pyridine or collidine, salts of the oxo-nitrile (4a) were formed exclusively. Similar solvent effects controlled the cyclisation of the cyano(pyrazol-5-ylhydrazono)acetate (2c), but the corresponding cyano(tetrazol-5-ylhvdrazono)acetate (2d) gave only the amino-ester (3d) in acetic acid or pyridine. 2-(1,2,4-Triazol-5-ylhydrazono)malononitrile (17) cyclised unambiguouly to 7-amino-1,2,4-trizolo[5,1-c][1,2,4]triazine-6-carbonitrile (18) in acetic acid or aqueous ethanol.Drastic hydrolysis of the hydrazones (2a) and (17) and the triazolo[5,1-c][1,2,4]triazines (3a), (4a), and (18) with 6N-hydrochloric acid gave a hydrate of 1,2,4-triazolo[5,1-c][1,2,4]triazin-7(4H)-one (24). Selective hydrolysis of the same triazolotriazines afforded intermediates which were identical with known derivatives and which served to establish the [5,1-c] geometry of ring fusion. Mass spectral fragmentation of 7-aminoazolo[5,1-c]-[1,2,4]triazines confirms that the azole ring is more stable than the 1,2,4-triazine ring on electron impact.

Synthesis of 2-acyl-3-hydroxyquinolines embodying a novel variant of the Smiles rearrangement

2-(2′-Nitrobenzoyl) derivatives of certain 1,3-diketones undergo base-catalysed cyclisation to hitherto inaccessible 2-acyl-3-hydroxyquinolines by a process explicable in terms of a new version of the Smiles rearrangement.