SYNTHESIS AND REACTIONS OF HALOAZODIENES - A NEW AND GENERAL-SYNTHESIS OF SUBSTITUTED PYRIDAZINES

The reaction of dihalohydrazones with Hunig's base gives 1-carbethoxy- 3-phenyl-4-haloazodienes in-situ, which were found to combine with a v ariety of electron rich olefins to yield halo-substituted tetrahydropy ridazines (Scheme 2 and Table 1). These haloazodiene cyclizations are best characterized as inverse electron demand, 4 + 2 hetero Diels-Alde r reactions that maintain a high degree of regio- and stereochemical c ontrol (Schemes 5 and 6). The chloro-substituted tetrahydropyridazines that are formed give high yields of substituted pyridazines upon trea tment with base (Table 1). The sequence of a chloroazodiene cyclizatio n to a tetrahydropyridazine followed by an aromatization constitutes a new and general synthesis of substituted pyridazines. In contrast to the haloazodiene cyclizations, the novel cyclization reactions of the in-situ generated 1-carbethoxy-3-phenyl-4,4-dichloroazodiene were foun d to give N-aminopyrroles and pyridazines when combined with acyclic e namines (Table 3). However, reactions with cyclic enamines gave the N- aminopyrroles, pyridazines, a dihydropyridazine as products as well as the noncyclized enamine intermediates (Table 4). The noncyclized enam ines could be converted to the N-aminopyrroles simply upon heating to higher temperatures, indicating a stepwise mechanism (Schemes 8 and 9) . The examples described here are the first reported cyclization react ions for dichloroazodienes.