Rationalisations among Heterocyclic Partition Coefficients Part 1: The π‐Value of Phenyl

Abstract

It is shown that πPh has a minimum theoretical value of ca. 1.7 in aromatic rings. This value is attained whenever phenyl is forced into a highly non‐planar conformation, as may happen through peri‐interactions or the heavy solvation of sterically hindering neighbouring groups. In the absence of such hindrance πPh will be greater, and can attain values as high as ca. 2.6 when there is no steric hindrance to coplanarity and two hetero‐atoms can be shielded. These and a number of intermediate situations are delineated; estimates of πPh are provided for each distinct case. The effect of phenyl substitution at sp3‐carbon is discussed in similar terms. It is shown that these variations make qualitative chemical sense and can be used for predictive purposes.

Partitioning and Lipophilicity in Quantitative Structure-Activity Relationships

“…However, from a consideration of other information, Dearden and O'Hara (147) concluded that the latter was the case. Lewis, Mirrlees, and Taylor (123,148) have elegantly rationalized the partition coefficients of nitrogen-containing heterocyclic compounds from a consideration of resonance, inductive, steric and hydrogen-bonding effects (separating the last into proton-donating and proton-accepting factors) and producing sets of equations for correction of heterocyclic r-values from the corresponding aromatic value.…”

Quantitative structure activity/retention relationships of imidazoline and alpha2 adrenergic receptors ligands

“…Prvi pristupi u odreñivanju lipofilnosti zasnivali su se na oblaganju stacionarne faze oktanolom, a kao eluent je korišćena voda ili pufer zasićeni oktanolom. 119,120 Glavni tehnički problem koji se javio u toku pripreme ovakvih kolona bila je nestabilnost samog oblaganja stacionarne faze.…”