Ms. South et al., SYNTHESIS AND REACTIONS OF HALOAZODIENES - A NEW AND GENERAL-SYNTHESIS OF SUBSTITUTED PYRIDAZINES, Journal of organic chemistry, 61(25), 1996, pp. 8921-8934
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.