title: Unusually high pyramidal geometry of the bicyclic amide nitrogen in a complex 7-azabicyclo[2.2.1]heptane derivative: Theoretical analysis using a bottom-up strategy.
abstract: The high pyramidalization of the bicyclic amide nitrogen found in the crystal structure of a dipeptide incorporating (1S,2S,4R)-N-benzoyl-2-phenyl-7-azabicyclo[2.2.1]heptane-1-carboxylic acid has been investigated using quantum mechanical calculations. More specifically, a bottom-up strategy based on the study of model molecules of progressive complexity has been used. First, an appropriate quantum mechanical method has been selected by examining the distortion of the amide bond in three simple model molecules. Next, the amide distortion induced by the norbornane ring has been evaluated by considering three different 7-azabicyclo[2.2.1]heptane amides. After this, the suitability of quantum mechanical calculations to predict the effect of the substituents on the pyramidalization of the bicyclic amide nitrogen has been investigated by comparing experimental and theoretical parameters for a number of compounds. Finally, the factors responsible for amide distortion in the (1S,2S,4R)-N-benzoyl-2-phenyl-7-azabicyclo[2.2.1]heptane-1-carboxylic acid derivative have been elucidated using a hierarchical approach. For this purpose, several derivatives were generated by removing or modifying the substituents attached to the 7-azanorbornane system. Results have been discussed in terms of intramolecular specific interactions.
authors.affiliation: Departament d'Enginyeria Química, E.T.S. d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, Diagonal 647, E-08028 Barcelona, Spain. carlos.aleman@upc.es
authors.forename: Carlos
authors.initials: C
authors.lastname: Alemán
authors.forename: Ana I
authors.initials: AI
authors.lastname: Jiménez
authors.forename: Carlos
authors.initials: C
authors.lastname: Cativiela
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Pérez
authors.forename: Jordi
authors.initials: J
authors.lastname: Casanovas
mesh_terms: D000577:Amides / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D000577:Amides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002264:Carboxylic Acids; C521639:N-benzoyl-2-phenyl-7-azabicyclo(2.2.1)heptane-1-carboxylic acid; D009584:Nitrogen