Mannich bases were prepared from quinolinols, isoquinolinols, phenols, biphenols, and ketones in order to have their antimicrobial properties evaluated. HE USE OF 3-azabicyclo[3.2.2]nonane (I), Talso known as AZBN, in the Mannich reaction was reported by Blanton and Nobles in 1962 (I). In biological screening, some of these Mannich bases were found to possess marked antimicrobial activity (2). As an extension of this study, AZBN, along with other bicyclic and heterocyclic amines, was condensed with moieties of known anti-infective agents utilizing the Mannich reaction ( ) in order to study their antimicrobial properties, i.e., antimalarial, antiamebic, and related effects. Quinine (11), a quinolylcarbinolamine containing a methoxy group on the quinoline nucleus linked by a secondary carbinol to a quinuclidine ring bearing a vinyl group, is an antimalarial that has been utilized since the year 1630 (4). This structure (11) served to provide the fountainhead of ideas for this work when a search of the literature revealed that many known anti-infectives have resulted from condensation of quinoline and phenolic compounds with aminomethyl moieties.
Since AZBN is a bicyclic amine, it is conceivable that this amine can be useful-along with other bicyclic and heterocyclic amines-in place of the quinuclidine moiety in quinine. With this in mind, a number of substituted phenols and compounds structurally related to quinine were synthesized; more specifically, the products were prepared by the condensation of quinolinols, isoquinolinols, phenols, biphenols, and ketones with 37% a.queous formaldehyde (formalin), and cyclic arnines.
Discussion
The o-and p-hydrogens in phenols are sufficiently active to react in the Mannich reaction (5). From 8-quinolinol and 5-isoquinolinol (Table ), mono- and disubstituted products are expected, while only