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On the basis of data obtained from microscopic examination, melting observations, cooling curves, X-ray analyses, and resistance measurements, phase diagrams have been proposed for the Th-Cb and Th-Ti alloy systems. Both are simple eutectic systems and have no terminal solid solubility or intermediate phases. The eutectic between thorium and columbium occurs at a composition of about 8 wt pet Cb and a temperature of 1435°C. The Th-Ti eutectic occurs at 1190°C at the composition 12 wt pet Ti. No change was observed in the transformation temperature of thorium in either system or in the titanium transformation.

RESEARCH in these Laboratories on new hypotensive drugs has in recent years centred on the development of compounds exhibiting both a high level of ganglion-blocking activity and good absorption after oral administration. The first phase of this work culminated in the discovery of 1:2:2:6:6:-pentamethylpiperidine, pempidine1. In clinical use the good absorption and conveniently rapid excretion characteristics of this drug combine to make it a useful advance in the management of essential hypertension2.

4-Mercaptocinnolines are obtained in good yield from the 4-hydroxy-compounds by reaction with phosphorus pentasulphide in pyridine. The corresponding amines are prepared readily from the mercapto-compounds by treatment with ammonia or primary amines. The amination reaction fails with nitro-4-mercaptocinnolines. The reaction of the 4-mercapto-derivatives with hydrazine, methylating agents, and Raney nickel is described. Treatment of 6-chloro-4-mercaptocinnoline with chlorine in acetic acid gave a good yield of 4,6-dichlorocinnoline and not the expected 4-sulphonyl chloride.

Das 1-Amino-pyridiniumkation (Ia) befindet sich in wasriger Losung bei hohem pH im Gleichgewicht mit Pyridin-( 1)-imid (II), das sich langsam zersetzt.

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Pyrrolidine congeners of the hypotensive drug “pempidine” (1,2,2,6,6-penta-methylpiperidine), have been made from γ-nitroketones, themselves readily available by Michael addition of s-nitroalkanes to α,β-unsaturated ketones. Reduction of the aliphatic or cycloaliphatic nitroketones with zinc and ammonium chloride gave cyclic nitrones (Δ1-pyrroline N-oxides). Addition of Grignard reagents or alkyl lithiums across the C=N bond furnished N-hydroxy-2,2,5,5-tetraalkylpyrrolidines, which on reduction gave the desired 2,2,5,5-tetraalkylpyrrolidines. Many of these and their N-alkyl derivatives showed hypotensive activity comparable with that of “pempidine”. Steric factors prevented either the nitrone cyclisation or the Grignard addition reaction with some cycloaliphatic nitroketones. In an alternative approach the direct reaction of the nitroketone with an excess of Grignard reagent gave, in addition to the expected N-alkylhydroxylamino tertiary alcohol, a fragrant-smelling basic compound, the structure of which was investigated.

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Several routes for the large scale preparation of 4,6-diaminocinnoline have been explored. The most satisfactory preparation involves conversion of diethyl mesoxalate phenylhydrazone, via the corresponding acid, into the acid chloride which is cyclised by reaction with titanium tetrachloride to give 4-hydroxycinnoline-3-carboxylic acid. Successive decarboxylation and nitration affords a mixture of nitro-compounds from which 4-hydroxy-6-nitrocinnoline is readily obtained. This is converted by thionyl chloride–phosphorus pentachloride into the 4-chloro-compound, and thence by reaction with ammonia in phenol into 4-amino-6-nitrocinnoline, whence catalytic reduction in dimethylformamide gives 4,6-diaminocinnoline in 11% overall yield.

The literature n.m.r. assignment for 4-cinnolones is revised. The spectra of substituted 4-cinnolones are used to confirm the gross structures of 4-cinnolones and to investigate the tautomerism of some sulphonic acid derivatives. The effect of substituents on chemical shifts and coupling constants in the cinnolone series is discussed.