Synthesis and kinetic studies on axially chiral heterocyclic compounds

Abstract

This thesis consists of two parts. In the first part, axially chiral (S)-5-methyl-3-(otolyl)oxazolidine-2,4-dione was synthesized as a single enantiomer. The optical stability of C-5 chiral center of the compound was tested in neutral, acidic and basic environments. It was found that C-5 center of the compound 1 was optically stable under neutral and acidic conditions, however, was labile under a basic environment. The lability of the center was tested through an enolization reaction by using the non-nucleophilic base, LDA. The enolization occurred slightly at -78 ºC, but complete racemization was observed at higher temperatures. The compound 1 was found to retain its integrity until 40-50 min range after the addition of the nuchleophilic base 0.4% (v/v) NaOH(aq). The ring opening of the compound was observed to occur after 40-50 min. The kinetics of racemization at C-5 of the ring opened product was also studied in the scope of the first part. The reductive ring opening reaction of the compound 1 was done with NaBH4. The examination of the optical stability of the C-5 chiral center of the product during the reaction revealed a slight racemization (90.21 : 9.79). The second part of the project comprises the racemic synthesis of the axially chiral 2-thioxo-3-(o-aryl)-quinazoline-4-ones and 2-(benzylthio)- 3-(o-aryl)-quinazolin-4-ones and the determination of their barriers to rotation by thermal racemization experiments. The energy barriers of 2-thioxo derivatives 2b-2e could not be determined either due to the decomposition at 110 ºC or stability to rotation. The free energy of activation barriers were determined for the 2-thioxo derivative 2a and for the thiobenzyl derivatives 3a, 3b, 3c, 3e, 3f and was found to be in the range 112.65-140.80 kJ/mol. The determined barriers of thiobenzyl derivatives showed a linear relation with the Van Der Waals radii of attached halogen substituents.