Synthesis of 8-Substituted 7-Azarutaecarpines

The synthesis of 8-substituted 7-azarutaecarpines 2 is described. These compounds were prepared by Fischer indolization of 3-amino-2-(1-phenylhydrazonoethyl)-4(3H)-quinazolinone 5, followed by cyclocondensation with a series of aliphatic, araliphatic or aromatic aldehydes and formic acid or a Vilsmeier–Haack reagent. The stereochemistry of compounds 2 was investigated by 1H NMR spectroscopy. It was found that the 8-substituents assume a quasi-axial position on the flattened boat conformation of ring C of 2, with the exception of ortho substituted phenyl groups, which occupy quasi-equatorial positions. Semi-empirical MO calculations support these conformational preferences.