Methylation of Sydnone N-Oxides:  Kinetic and Thermodynamic Control in the Alkylation Site of an Electron-Rich Heterocycle

D. Scott Bohle,* Lindsey E. McQuade, Inna Perepichka, and Lijuan Zhang
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, H3A 2K6, PQ, Canada
J. Org. Chem., 2007, 72 (10), pp 3625–3631
DOI: 10.1021/jo062235k
Publication Date (Web): April 18, 2007
Copyright © 2007 American Chemical Society
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, scott.bohle@mcgill.ca

Abstract

Abstract Image

Methylation of the anionic 4-methylcarboxy 1,2,3-oxadiazolate 3-oxide occurs at either the disubstituted ring nitrogen or the oxygen of the N-oxide depending upon the conditions and reagents employed. Alkylation with methyl iodide leads to N-alkylation, while dimethyl sulfate gives O-alkylation and trifluoromethanemethylsulfonate gives a mixture of the two products. The regioselectivity of these methylations has been confirmed by X-ray diffraction of the two products, and these are in turn correlated with their theoretically predicted (B3LYP//6-311++G**) relative energies and vibrational spectra. Theoretically, N-alkylation is expected to give an isomer that is over 10 kcal mol-1 more stable than the O-alkylated product. As a neat melt the kinetic O-alkylation product cleanly isomerizes in 2 h when heated to 140 °C to give the thermodynamic N-methylated isomer. Taken together the results illustrate the remarkable new sydnone N-oxide derivatives which are readily accessed in this chemistry, with the N-alkylation of the sydnone N-oxide, corresponding to the first case of such an N-alkylation for a diazenium diolate.

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History

  • Published In Issue May 11, 2007
  • Received October 27, 2006

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