Nucleophilic Attack on the Carbon–Nitrogen Double Bond Leading to Tetrahedral Intermediates with Conformationally Restricted Stereochemistry

James E. Johnson; Lei Lu; Yi Li; Mei Hou; Jeffrey E. Rowe

doi:10.1071/CH08312

RESEARCH ARTICLE

Previous Next Contents Vol 61(11)

Nucleophilic Attack on the Carbon–Nitrogen Double Bond Leading to Tetrahedral Intermediates with Conformationally Restricted Stereochemistry

James E. Johnson ^A ^C , Lei Lu ^A , Yi Li ^A , Mei Hou ^A and Jeffrey E. Rowe ^B

+ Author Affiliations

- Author Affiliations

^A Department of Chemistry and Physics, Texas Woman’s University, Denton, TX 76204-5859, USA.

^B Department of Chemistry, LaTrobe University, Vic. 3086, Australia.

^C Corresponding author. Email: jjohnson@mail.twu.edu

Australian Journal of Chemistry 61(11) 888-893 https://doi.org/10.1071/CH08312
Submitted: 22 July 2008 Accepted: 25 September 2008 Published: 5 November 2008

Abstract

Methoxide ion substitution on 4-chloro-1H-2,3-benzoxazine 4 has been investigated. The rates of cyclization have been measured for (Z)- and (E)-O-(2-hydroxyethyl)benzohydroximoyl halides (PhC(X)=NOCH₂CH₂OH; X = Cl or Br) using potassium t-butoxide to generate alkoxide ions from the alcohols. The element effect for the Z and E isomers are k_ZBr/k_ZCl = 3.08 and k_EBr/k_ECl = 2.38. The Z-to-E rate ratios are 0.25 (chlorides) and 0.33 (bromides). These reactions are proceeding by rate-determining nucleophilic attack by the alkoxide ion on the carbon–nitrogen double bond (A_N# + D_N). The restricted stereochemistry of the tetrahedral intermediates suggests that the E-hydroximoyl bromide and chloride may be undergoing unassisted ionization to form a zwitterionic intermediate that leads to product. Alternatively, the chair conformation of the tetrahedral intermediate may be undergoing a ring flip to a boat conformation in which there are antiperiplanar electron pairs that assist in the ionization of the bromide or chloride ion.

Acknowledgements

Acknowledgement is made to the Minority Biomedical Research Support Program of the National Institutes of Health (NIH-MBRS Grant GM08256), The Robert A. Welch Foundation, and the Texas Woman’s University Research Enhancement Program for support of the present work. J.E.R. thanks the Texas Woman’s University for hospitality during the completion of part of this work.

References

Nucleophilic Attack on the Carbon–Nitrogen Double Bond Leading to Tetrahedral Intermediates with Conformationally Restricted Stereochemistry

Abstract

Acknowledgements

Subscriber Login