Synthesis and barriers to rotation in axially chiral barbituric and thiobarbituric acid derivatives

Abstract

In this study, 5,5-dimethyl-1-(0-bromopheny1)-2-thiobarbituric acid has been synthesized by the reaction of the corresponding N-o-arylthiourea with the dimethylmalonic acid in the presence of acetylchloride. The o-fluoro and the o-chloro substituted 5,5-dimethyl-1-(0-ary1)barbituric acids have been synthesized by the direct conversion reaction of the thiocarbonyl in the 5,5-dimethyl-1-(0-fluoropheny1)-2- thiobarbituric and 5,5-dimethyl-1-(0-chloropheny1)-2-thiobarbhric acid, respectively, into a carbonyl group by treatment with bromine in 90 per cent acetic acid. In all of the trials the yielded products were composed of the target compounds and the thiobarbiturate precursor. However, the two components could not be separated from each other neither by crystallization nor by chromatographic methods. The studied barbituric and -2-thiobarbituric acids are chiral due to nonplanar ground states. The aim of this project is to determine the activation energies for the racemization of these compounds. In this respect, the activation barrier for the 5,5-dimethyl-1-(0- fluoropheny1)barbituric acid has been determined by using dynamic NMR spectroscopy, whereas the barrier for the 5,5-dimethyl-1-(0-bromopheny1)-2-thiobarbituric has been determined by thermal racemization subsequent to the separation of the enantiomers of this compound on the chiral sorbent, cellulose tris(3,5-dimethylphenyl) carbarnate. The required separation of the enantiomers for the thermal racemization of $5-dimethyl-1-(0- chloropheny1)barbituric acid could not be achieved by liquid chromatography and therefore the barrier to rotation for this compound could not be determined. The obtained barrier value for the 5,5-dimethyl-1-(0-bromopheny1)-2-thiobarbituric acid has been compared to the literature values for the o-chloro and the o-fluoro derivatives of $5-dimethyl-1-(0-ary1)-2-thiobarbituric acid and to the literature values for the ohalogen substituted 5,5-dimethyl-3-(0-ary1)-2,4-oxazolidinedione derivatives and a similar relationship between the size of the o-substituents and the barrier values has been observed. Using this relationship, the yet uncalculated barrier values for the o-halogen substituted 5,5-dimethyl- 1 -(o-ary1)barbituric acids have been estimated.