title: Application of 1,1-ADEQUATE, HMBC, and Density Functional Theory To Determine Regioselectivity in the Halogenation of Pyridine N-Oxides.
abstract: The 1,1-ADEQUATE spectrum clearly shows specific two-bond proton to carbon correlations to unequivocally distinguish the major and minor regioisomers of ortho-halogenated pyridines and to aid in assignment of the corresponding proton and carbon chemical shifts. M06-2X/6-31+G(d,p) free energies of the regioisomeric intermediates arising from deprotonation correctly predict the experimentally observed preference and thus can be used to tune the substituent pattern to yield a desired regiochemical outcome.
authors.affiliation: Attribute Sciences, ‡Molecular Engineering, Therapeutic Discovery, and §Drug Substance Technologies, Amgen, Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Tsang-Lin
authors.initials: TL
authors.lastname: Hwang
authors.affiliation: Attribute Sciences, ‡Molecular Engineering, Therapeutic Discovery, and §Drug Substance Technologies, Amgen, Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bartberger
authors.affiliation: Attribute Sciences, ‡Molecular Engineering, Therapeutic Discovery, and §Drug Substance Technologies, Amgen, Inc. , One Amgen Center Drive, Thousand Oaks, California 91320, United States.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen