Synthesis and reactions of thioureas, their cyclized derivatives and oxazolidindiones

Abstract

In this study, several single enantiomer thioureas were synthesized and converted to their cyclic derivatives: 2-imino-thiazolidin-4-ones and 5-benzylidene derivatives. The conformations of the thioureas were determined in solution and in the solid state. In solution; an interconversion between the E,Z and Z,E conformations was observed with ΔG≠ values of around 50 kJ/mole. However in the solid state X-Ray crystal structure analyses revealed that they possess a Z,Z conformation. The thiazolidin-4-ones were found to be present only in the anti-conformation. Chiral hemiaminals were synthesized from the corresponding 2-iminothiazolidine-4-ones by LiAlH4 reductions stereoselectively and were converted to single enantiomer thiazol-2-imines by a water elimination reaction. The optical purities of thiazol-2-imines were proven by polarimetric measurements. The kinetics of the dehydration reactions which occured spontenaously both in the solid state and in solution were followed by time dependent 1H NMR spectroscopy. The corresponding first order rate constants and free energies of activation for the conversions were reported. It was found that the N-naphthalen-1-yl)ethyl derivatized hemiaminals were the most stable of all, the half-lives amounting to 267 days in the solid state and 96 hours in soluton. A series of axially chiral pyridine compounds carrying 2-iminothiazolidin-4one core were also reduced to their hemiaminal derivatives using LiAlH4. Due to the restricted rotation around the N3-aryl single bond, the M/P isomerization was observed. Single enantiomers of the new 5-methyl-3-aryloxazolidine-2,4-diones were synthesized by an asymmetric synthesis using chiral pool strategy and their optical purities were proven. Enantiomerically pure 5-methyl-3-aryloxazolidine-2,4-diones were reduced to their hemiaminal derivatives and ring opening products in the presence of LiAlH4 and NaBH4, respetively. Partial racemization was observed due to enolization of the molecules because of the acidic -hydrogen at C-5 of the ring during these reactions.