Estimate of Donor and Acceptor Sites Using Alternating Polarity Principle. Application to Pyridine Ring Construction

On the basis of the polarity alternation rule a quantitative model for the survey of the best donor and acceptor sites in polar organic molecules was developed. To this aim the following rules were suggested: (i) how to decrease induced polarity through the chain, (ii) how to evaluate the interaction between native and induced polarities; and (iii) how to take polar conflicts into account. The best donor and acceptor sites were assigned from literature data to the training set of 61 reagents used for pyridine and pyrrole syntheses (containing carbonyl, cyano, ester, and amino groups). The best correspondence between calculated and assigned ratings of best polar sites was determined using genetic algorithm. Four variables of the model and seven native bond polarities were included in the optimization. The fitness function was designed to reflect the degree of correspondence between calculated and experimental ratings. About 90% of compounds and 60% of reactions were correctly optimized by the obtained set of parameters.