Factors Determining the Stereochemical Structure of 2-(Phosphorus Substituted) Methylidene-thiazolidine- 4-ones in Solid State and in Solution

Abstract

Regioselective synthesis of novel 2-(phosphorus substituted) methylidene-thiazolidine-4-ones 5a–c was performed via condensation of phosphorus-substituted acetic acid thioamides 4a–c with dimethyl acetylenedicarboxylate. Thiazolidine-4-ones 5a,b bearing thiophosphoryl or dithiophosphoryl moiety were obtained as E,Z-isomers while their analog 5c with triphenylphosphonium group was formed as a Z,Z-isomer. The structures of thiazolidin-4-ones 5a – c obtained were determined by single crystal X-ray diffraction. According to quantum-chemical calculations, the isomers observed in the solid state are thermodynamically more stable. In solution, thio- and dithiophosphorylated thiazolidinones 5a , b undergo E,Z → Z,Z isomerization relative to C ² carbon atom of the heterocycle proceeding via an imine–enamine mechanism.

Keywords:

• ab initio calculations
• dimethyl acetylenedicarboxylate
• isomerization
• 2-(phosphorus-substituted)methylidene-thiazolidine-4-ones
• regioselectivity
• (thio)phosphoryl acetic acid thioamides

Dedicated to Professor Marian Mikołajczyk, CBMiM PAN in Łódź, Poland, on the occasion of his 70th birthday.

This work was partially supported by the Russian Basic Research Foundation (grant No. 05-03-32692). We are grateful to Mrs. N. White (Department of Chemistry and Biochemistry, University of Maryland) for her helpful comments.

Notes

^a X is sulfur in E,Z- 5a and oxygen in Z,Z -2a.

^a The crystallographic data have been deposited with the Cambridge Crystallographic Data Center. Copies of this information may be obtained free of charge from: The Director, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: [phone]; e-mail: [email protected] or http://www.ccdc.cam.ac.uk).