Conformation Analyses, Dynamic Behavior, and Amide Bond Distortions of Medium-sized Heterocycles. 2. Partially and Fully Reduced 1-Benzazocines, Benzazonines, and Benzazecines

• Published in: Journal of organic chemistry Vol. 70; no. 5; pp. 1552 - 1557
• Main Authors: Qadir, Maryiam, Cobb, Jonathan, Sheldrake, Peter W, Whittall, Neil, White, Andrew J. P, Hii, King Kuok (Mimi), Horton, Peter N, Hursthouse, Michael B
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.03.2005; Amer Chemical Soc
• Subjects: Amides - chemistry; Azo Compounds - chemical synthesis; Azo Compounds - chemistry; Azocines - chemical synthesis; Azocines - chemistry; Chemistry; Chemistry, Organic; Crystallography, X-Ray; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - chemistry; Magnetic Resonance Spectroscopy; Models, Chemical; Models, Molecular; Molecular Conformation; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Structure-Activity Relationship; Temperature; Chemical solution; Correlation; Stability; Molecular structure; Nitrogen heterocycle; Conformational analysis; Theoretical study; Distortion; NMR spectrometry; X ray diffraction; Solid state; Force field method; Carboxamide; Ring strain; Chemical synthesis; Conformation
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo048117j

Partially and fully reduced forms of benzo-fused eight- to ten-membered nitrogen heterocycles (1-benzazecines, 1-benzazonines and 1-benzazecines) have been prepared. Conformational features, transannular distances and dynamic behavior were studied using X-ray crystallography and VT NMR spectroscopy. The amide moiety in the nine-membered benzazonine ring 5b favors N-pyramidization, whereas the ten-membered benzazecine 5c adopts an amide twist. Molecular mechanics calculations reveals a correlation between the amide twist (τ) and ring stability. The dynamic behavior of the heterocycles in solution were also found to be dependent on the extent and nature of the amide distortion. We thus conclude that ring strain of these medium-sized heterocyclic rings is relieved through amide distortion, which leads to a more stable structure.