Investigations of the Richter reaction in a series of vicinal alkynylpyrazolediazonium salts

Abstract

All positional isomers of vic-alkynylaminopyrazoles, when treated with sodium nitrite in hydrochloric or hydrobromic acid, are transformed into pyrazolopyridazines via cyclisation of the corresponding alkynylpyrazolyldiazonium salts. The ease of cyclisation was found to depend markedly on the position of the alkynyl and diazonium groups around the pyrazole nucleus: 4-alkynylpyrazole-5-diazonium salts derived from the corresponding 4-alkynyl-5-aminopyrazoles 1a–c cyclized at 0–20 °C to 4-chloro- and 4-bromo-1H-pyrazolo[3,4-c]pyridazines 2a–c and 3a; the heterocyclization of 5-alkynylpyrazole-4-diazonium salts 5a,b required heating to 100–105 °C and gave 7-chloro-1H-pyrazolo[4,3-c]pyridazines 6a,b in good yield. The cyclisation of 1-methyl-3-alkynylpyrazole-4-diazonium salts 8a,b was accompanied by methyl group migration towards the neighbouring nitrogen atom to give the same 7-chloro-1H-pyrazolo[4,3-c]pyridazines 6a,b arising from cyclisation of the 5-alkynylpyrazole-4-diazonium salts 5a,b. When treated with sodium hydrogen carbonate, the 1,5-dimethylpyrazol-4-diazonium salts 8a–c gave the 5-(pyrazol-4-ylazomethyl)pyrazole-4-diazonium chloride derivatives 9a–c which cyclized in the presence of base to give the corresponding 6-(pyrazol-4-ylazo)-4H-pyrazolo[4,3-c]pyrazoles 10a–c.

In contrast, the heterocyclization of 4-alkynylpyrazole-3-diazonium salts derived from 4-alkynyl-3-aminopyrazoles 11a,b at 50–60 °C gave 4-hydroxy-2H-pyrazolo[3,4-c]pyridazines 12a,b as the major components together with the corresponding 6-halogeno-pyridazines 13a,b and 14a as minor components.

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