Antagonistic or Non-Cooperative Substitutions

Substitution reactions of compounds having an antagonistic orientation of substituents require a more careful analysis. If the substituents are identical, as in example 1 below, the symmetry of the molecule will again simplify the decision. When one substituent has a pair of non-bonding electrons available for adjacent charge stabilization, it will normally exert the product determining influence, examples 2, 4 & 5, even though it may be overall deactivating (case 2). Case 3 reflects a combination of steric hindrance and the superior innate stabilizing ability of methyl groups relative to other alkyl substituents. Example 6 is interesting in that it demonstrates the conversion of an activating ortho/para-directing group into a deactivating meta-directing "onium" cation [–NH(CH₃)₂⁽⁺⁾ ] in a strong acid environment.