Which functional group gets halogenated first?
Babak Borhan and colleagues from Michigan State and Dow may have your answer. In a recent JACS full article, they disclose the HalA (halenium affinity) scale, a DFT-calculated delta to describe the relative reactivity of various groups to an incoming halogen source. They back up their calculations with NMR competition studies, showing, for example, that two structurally similar molecules have a rather skewed 7:1 equilibrium, as predicted by a 1.1 kcal / mol difference in HalA:
|Borhan et. al., JACS 2014|
I'm certain even more detailed versions of this chart are currently underway. I wonder how well it would extend to prediction of methyl or trifluoromethyl group additions?