Elucidation of the Mechanism for the S–N-type Smiles Rearrangement on Pyridine Rings

Jinghua Li; Lushan Wang

doi:10.1071/CH08205

RESEARCH ARTICLE

Previous Contents Vol 62(2)

Elucidation of the Mechanism for the S–N-type Smiles Rearrangement on Pyridine Rings

Jinghua Li ^A and Lushan Wang ^A ^B

+ Author Affiliations

- Author Affiliations

^A College of Life Science, Shandong University, Jinan 250100, China.

^B Corresponding author. Email: lswang@sdu.edu.cn

Australian Journal of Chemistry 62(2) 176-180 https://doi.org/10.1071/CH08205
Submitted: 14 May 2008 Accepted: 2 December 2008 Published: 19 February 2009

Abstract

The Smiles rearrangement (SR) is an important strategy for synthesizing heterocyclic compounds. Many pyridine moiety-containing complexes are biologically active. Although the success has been archived in the development of the SR on the pyridine ring to obtain pyridine moiety-containing heterocyclic compounds, not much is known about the detailed SR mechanism. Here, we report a theoretical study on a typical S–N-type SR reaction involved in the synthesis of thiazinone-fused pyridines. We studied both the ipso-SR process and the direct nucleophilic substitution reactions on the ortho-positions to rationalize the experimentally observed ipso-SR product. The calculated results show the ipso-SR consists of two elementary steps, the intramolecular ipso-position substitution and subsequent ring closure, and the barrier for the rate-determining step is 65.98 kJ mol^–1 and the overall reaction is exothermic by 116.94 kJ mol^–1, confirming the reaction is kinetically feasible and thermodynamically favourable under mild experimental conditions (such as controlled microwave heating). The present results provide a clear picture for understanding the S–N-type SR on the pyridine ring to synthesize pyridine moiety-containing heterocycles.

Acknowledgements

The work described in the present paper is supported by the National Natural Science Foundations of China (grant nos 20773078 and 30870044), and the Innovation Foundation of Science and Technology for Undergraduates in Shandong University. The authors also acknowledge the Institute of Theoretical Chemistry at Shandong University for the computational resources where all the calculations were performed.

References

Elucidation of the Mechanism for the S–N-type Smiles Rearrangement on Pyridine Rings

Abstract

Acknowledgements

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