title: Using the general-purpose reactivity indicator: challenging examples.
abstract: We elucidate the regioselectivity of nucleophilic attack on substituted benzenesulfonates, quinolines, and pyridines using a general-purpose reactivity indicator (GPRI) for electrophiles. We observe that the GPRI is most accurate when the incoming nucleophile resembles a point charge. We further observe that the GPRI often chooses reactive "dead ends" as the most reactive sites as well as sterically hindered reactive sites. This means that care must be taken to remove sites that are inherently unreactive. Generally, among sites where reactions actually occur, the GPRI identifies the sites in the molecule that lead to the kinetically favored product(s). Furthermore, the GPRI can discern which sites react with hard reagents and which sites react with soft reagents. Because it is currently impossible to use the mathematical framework of conceptual DFT to identify sterically inaccessible sites and reactive dead ends, the GPRI is primarily useful as an interpretative, not a predictive, tool.
authors.affiliation: Computational Materials Science Research Team, AICS, RIKEN, Kobe, Hyogo, 650-0047, Japan. james.anderson@riken.jp.|Computational Condensed Matter Physics Laboratory, RIKEN, Wako-shi, Saitama, 351-0198, Japan. james.anderson@riken.jp.
authors.forename: James S M
authors.initials: JS
authors.lastname: Anderson
authors.affiliation: ASRC Federal Technical Services, 289 Dunlop Blvd, Huntsville, Al, 35824, USA.
authors.forename: Junia
authors.initials: J
authors.lastname: Melin
authors.affiliation: Department of Chemistry & Chemical Biology, McMaster University, Hamilton, Ontario, L8S 4M1, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Ayers
mesh_terms: D000465:Algorithms; D008956:Models, Chemical; D008958:Models, Molecular; D008962:Models, Theoretical
keywords: Conceptual density functional theory; Electrostatic potential; Fukui function; General purpose reactivity indicator; Reactivity transition table