A new cinnoline synthesis. Part III. Alternative routes to 4-hydroxy-6-nitrocinnoline and 4,6-diaminocinnoline

Abstract

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.