title: Studies on the regioselective nucleophilic aromatic substitution (S(N)Ar) reaction of 2-substituted 3,5-dichloropyrazines.
abstract: Differences in regioselectivity were observed during the S(N)Ar reaction of amines with unsymmetrical 3,5-dichloropyrazines. This study revealed that when the 2-position of the pyrazine was occupied with an electron-withdrawing group (EWG), nucleophilic attack occurred preferentially at the 5-position. When the 2-position was substituted with an electron-donating group (EDG), nucleophilic attack occurred preferentially at the 3-position. These results are reported along with a computational rationale for the experimental observations based on the Fukui index at the reacting centers.
authors.affiliation: La Jolla Laboratories, Pfizer, Inc., 10770 Science Center Drive, San Diego, California 92121, United States. stephanie.scales@pfizer.com
authors.forename: Stephanie
authors.initials: S
authors.lastname: Scales
authors.forename: Sarah
authors.initials: S
authors.lastname: Johnson
authors.forename: Qiyue
authors.initials: Q
authors.lastname: Hu
authors.forename: Quyen-Quyen
authors.initials: QQ
authors.lastname: Do
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Braganza
authors.forename: Shijian
authors.initials: S
authors.lastname: Ren
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wan
authors.forename: Baojiang
authors.initials: B
authors.lastname: Zheng
authors.forename: Darius
authors.initials: D
authors.lastname: Faizi
authors.forename: Indrawan
authors.initials: I
authors.lastname: McAlpine
mesh_terms: D000588:Amines / Q000737:chemistry*; D004583:Electrons; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry*; D010084:Oxidation-Reduction; D011719:Pyrazines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000588:Amines; D006843:Hydrocarbons, Chlorinated; D011719:Pyrazines