Jacek Bojarski

Recent Progress in Barbituric Acid Chemistry

Publisher Summary This chapter provides information on the chemistry and pharmacology and physicochemical properties of barbiturates, along with the tautomerism and solvation of the barbituric acid ring. Barbituric acid exists in the solid state in the trioxo structure. NMR investigation of the oxo-hydroxy equilibrium indicates that only the oxo form is present in a solution in anhydrous DMSO. Several spectral properties of the barbituric acid are discussed using UV spectra, infrared and Raman spectroscopy, 1 H-NMR spectroscopy, 13 C-NMR spectroscopy, and mass spectrometry. In the crystalline state, barbiturates show several modes of intermolecular hydrogen bonding, which differ by the number of hydrogen bonds formed between the NH and CO groups. These hydrogen bonds are responsible for layer packing in the crystal lattice. Weak intermolecular van der Waals interactions of carbonyl groups are also responsible for the three-dimensional packing of the molecules in the crystal structure.

Resolution of Mephenytoin and Some Chiral Barbiturates into Enantiomers by Reversed Phase High Performance Liquid Chromatography via β-Cyclodextrin Inclusion Complexes

Abstract β-Cyclodextrin as the chiral mobile phase component was used for resolution of mephenytoin and some barbiturates (antidepressant drugs) into enantiomers on LiChrosorb RP 18 column. The effects of β-cyclodextrin concentration on the capacity factors were investigated and the stability constants as well as capacity factors of β-cyclodextrin complexes were calculated. It has been found that β-cyclodextrin complexation results in a distinct enantioselectivity in the case of mephenytoin and barbiturates containing a chiral center in the pyrimidine ring. Results are discussed in the light of two phenomena influencing resolution: adsorption of inclusion complexes on the stationary phase and complexation process in the mobile phase solution.

Application of α- and β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin as mobile phase components for the separation of some chiral barbiturates into enantiomers by reversed-phase high-performance liquid chromatography

Abstract Using LiChrosorb RP-18 as the stationary phase, systematic studies were performed on the changes in the capacity factors of a series of hydantoin and barbituric acid derivatives (including some therapeutically useful drugs) with variation in the concentrations of α- and β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin in the mobile phase.It has been found that both β-cyclodextrin and its dimethyl derivative exhibit enantioselectivities towards hydantoins and barbiturates that contain a chiral carbon atom in the heterocyclic ring. No selectivity was observed with α-cyclodextrin. Owing to the strong adsorption of dimethylated β-cyclodextrin from its dilute solutions on an ODS surface, a new mechanism for the separation of enantiomeric barbiturates was established.

Resolution of chiral barbiturates into enantiomers by reversed-phase high-performance liquid chromatography using methylated β-cyclodextrins

The correlation between the capacity factors of enantiomers of chiral barbiturates and the concentrations of beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin dissolved in the mobile phase was studied using LiChrosorb RP-18 as the stationary phase. Owing to the very strong adsorption of permethylated beta-cyclodextrin on the ODS surface a chiral stationary phase is generated dynamically and forms complexes with the solutes; this mechanism has been found to be the only factor responsible for the chiral recognition of the investigated compounds at all applied concentrations. The inclusion of barbiturates in the cavities of permethylated beta-cyclodextrin involves a distinct and entirely new kind of enantioselectivity compared with that observed for beta-cyclodextrin and its dimethyl derivative. Using permethylated beta-cyclodextrin baseline resolutions have been obtained with barbiturates containing a chiral centre in the heterocyclic ring or in the aliphatic side-chain.

Simple Chiral Liquid Chromatographic Enantioseparation of Some Racemic Antiepileptic Drugs

Abstract Cellulose tris (4-methylbenzoate) known as Chiralcel OJ chiral stationary phase (CSP) has been successfully used for the enantioseparation of three clinically used antiepileptic drugs namely, mephobarbital, mephenytoin and benzonal. The chemical structure-chiral recognition mechanisms related to the enantiomeric elution order of these dns are discussed.

Photoinduced stereospecific formation of substituted hydantoin from hexobarbital

Abstract The irradiation (253.7 nm) of the anion of S( + )-5-(1′-cyclohexenyl)-1,5-dimethyl-2,4,6(1H,3H,5H)-pyrimidinetrione (the well-known drug, hexobarbital ( 1 )) induces stereospecific conversion to R( + )-5-(1′-cyclohexenyl)-3,5-dimethyl-2,4-imidazolidinedione ( 2 ). Partial inversion of the configuration of 1 (2%–5%) is also observed. The overall quantum yield of photolysis vs . temperature relationship can be interpreted in terms of reversible homolytic cleavage of the C4–C5 bond of 1 . An extended mechanism of reaction leading to hydantoin ( 2 ) and including inversion of configuration of the substrate is proposed. The features and applications of the stereospecific contraction of the pyrimidine ring of 1 are also discussed.