Polarity Rules in Computer Design of Heterocycles

Qualitative polarity rules for heterocyclic ring synthesis via polar reactions of cyclization or recyclization are discussed. The main idea is the application of general definition of consonant and dissonant structures to acyclic chains and cyclic heteroaromatics and analysis of interconversion of this two combinatorial properties. Appearance of dissonant structure from consonant one seems to be forbidden process. Brief review of recent author's works show prospects of application this rules to computer assisted heterocyclic synthesis. One actual problem of computers assisted organic synthesis is prediction of optimal routes for the synthesis of the given heterocyclic target. Usual principles of heterocyclic synthesis include two general methods of the target structure formation: 1) by cyclizations of acyclic precursors, 2) by ring transformations of another heterocycles. Most of such reactions are usually polar on nature, and permit one to clearly identify the disposition of electroand nucleophilic centers in the target and reactants. The goal of this communication is to provide the general qualitative analysis of polarity rules for these methods of heterocyclic synthesis, and to prove their usefulness in computer synthesis planning. Heteroaromatic systems can be roughly classified into the two large classes: The consonant heteroaromatic structures are: those with evenmembered rings (e.g. pyridines), and/or with alternating disposition of heteroatoms (e.g. pyrimidine), and/or with "normal" disposition of polar donor and acceptor groups. "Normal" disposition means odd chain betweeen any pair of electronegative heteroatoms X, independently on their presence as endocyclic heteroatom in the ring, donor atom as the exo-group, or terminal electronegative atom of acceptor group. Any consonant structure can be presented as bichromatic graph, so that any electronegative heteroatom has the same color. The color may be associated with alternation of formal charges (+ and -), of acceptor/donor and/or of electro/nucleophilic centers in consonant molecule. 746 © 1995 American Institute of Physics