Abstract
Anhydro 4-hydroxy-pyrido [1, 2-b] pyridazinium hydroxide derivatives were prepared starting with ethyl 2-piperidine-carboxylate (I). I was, via the N-nitroso compound (II), converted into the corresponding N-amino derivative (III), which was condensed with ethyl acetoacetate to give ethyl 1-(ethoxycarbonyl-isopropylidene) amino-2-piperidine carboxylate (IV) in a good yield. The Dieckmann condensation of IV led to the corresponding cyclic compound (V), mp 152-153°, contaminated with a small amount of a 4-hydroxy-pyrido [1, 2-b] pyridazinium hydroxide derivative (VI), mp 135-136° (anhydronium base). V and VI are transmutable each other by oxido-reduction. VI was readily hydrolysed to the corresponding carboxylic acid (VII), which was decarboxylated to anhydro 4-hydroxy-2-methyl-5, 6, 7, 8-tetrahydro-pyrido [1, 2-b] pyridazinium hydroxide (VIII), mp 142°. The C3-position of VIII was subject to both the electrophilic and the nucleophilic attacks ; VIII was readily brominated with bromine to give the 3-bromo compound (IX) which led, via the corresponding thiouronium bromide, to the 3-mercapto compound (XII), and to the anilino derivative (X) reacted with aniline. Furthermore, VIII was treated with hydrogen peroxide to give 3-hydroxy derivative (XV). The above synthesis has been applicable to a general method for the preparation of anhydro 1-substituted or 1, 6-disubstituted 5-hydroxy-pyridazinium hydroxides, a type of zwitterionic heterocyclic compounds.
