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89 Abstract Biological Activity and Analytical BIOLOGICAL ACTIVITY AND ANALYTICAL CHARACTERIZATION OF BARBITURIC ACID Vijaya Laxmi S, Janardhan B, Rajitha B ijcrr Vol 04 issue 07 Department of Chemistry, National Institute of Technology, Warangal Category: Review Received on:12/12/11 E-mail of Corresponding Author: [email protected] Revised on:15/01/12 Accepted on:28/02/12 ABSTRACT Earlier literature reports imply that this scaffold is having activity on central nervous system. According to the present studies it has become an attractive target for the development of drugs, which hold variety of biological activities. Derivatives of barbituric acid have attracted the attention of researchers in synthetic organic chemistry, as well as medicinal chemistry, for a long time as a result of their exceptionally diverse biological activity. Present review highlights the importance of the barbituric acid in the present context. ____________________________________________________________________________________ Keywords: Barbituric acid, Biological activity, biological activities that stand apart from Spectral studies, X-ray Crystallography, Dye previous medical utilization of barbituric acid properties. derivatives.4 However it is a precursor to barbituric acid derivatives widely been used in 1 INTRODUCTION the manufacturing of plastics,5 textiles,6 Barbituric acid (BA) is documented as the parent polymers,7 and pharmaceuticals,8-9 dental compound of the barbiturate drugs. (Fig.1). It is materials,10 water thinned or oil-based inks,11 used in the production of riboflavin, Nembutal, and as polymerization catalysts.12 In view of the and Phenobarbital.1-2 This class of compounds above observations it is worthwhile to make a has been extensively used in medical and brief review on it. biological studies for many years, the best 2 Barbiturates known of which is their sedative action in the 2.1 Chemistry of Barbiturates central nervous system3 (CNS). Barbituric acid an organic compound of the pyrimidine family,13 chemically called as 2,4,6 O O trioxopyrimidine, a class of compounds with a characteristic six-membered ring structure N N H H composed of four carbon atoms and two O nitrogen atoms. Compounds possessing the Fig.1 C2=O group are known as oxybarbiturates, and It was demonstrated that some barbituric acid those having a C2=S group are known as derivatives have new and very interesting thiobarbiturates. 89 International Journal of Current Research and Review www.ijcrr.com Vol. 04 issue 07 April 2012 R R1 R 5 5 O O O O O O O O 5 5 4 6 4 6 4 6 4 6 HN 2 NH HN 2 NH N 2 N HN 2 NH 3 1 3 1 3 1 3 1 O O O O 1 2 3 4 Fig.2 The thiobarbiturates generally have higher lipid Knoevenagel condensations of barbituric acid solubilities than their corresponding under solid state, synthesis was achieved by oxybarbiturates. The α-carbon has a reactive Gerd Kaupp et al.22 hydrogen atom and is quite acidic, variety of 2.4 Tautomerism barbituric acid drugs were synthesized by Barbituric acid exists in the solid state in the employing Knoevenagel condensation. Their trioxo structure as shown by X-ray23-24 and 14N- biological activities varied when substituent‘s NQR25 methods. NMR investigation of the oxo- introduced on two Nitrogen atoms and 5th hydroxy equilibrium also indicates that only the position of barbituric acid. (Fig. 2) oxo form is present in a solution in anhydrous 2.2 Synthesis of Barbituric acid DMSO.26, 27 BA exist as single molecular Several synthetic methods are available in the species in the gas phase with trioxo tautomers literature. In 1862, A. V. Baeyer accidentally being the most stable. This conclusion was discovered the barbituric acid, by combining reached on the basis of calculated tautomer urea and malonic acid on condensation energies and FT-IR spectra.28 Igor Novak et al. reaction.14 have used G3MP2B3 method to calculate Gibbs 2.3 Synthesis of Barbiturate drugs free energies of the two possible tautomers Barbituric acid condense smoothly with established that keto tautomers are more stable aldehydes under moderate conditions,15-17 than enols by 36.8 and 36.7 kJ/mol, yielding 5-ylidene.The presence of low electron respectively.29 Recently Michale R.Chierothi et density at the C-5 position in the exocyclic C=C al. reported that by griding a commercial sample bond, owing to conjugation with the carbonyl of Barbituric acid in its trioxo form for 24 h, a groups in the 4 and 6-positions, causes the new compound has been isolated. The new nucleophilic addition reaction. Several literature phase has been identified as trihydroxy isomer. procedures were reported for the Knoevenagel 30 Ab inito and density functional theory (DFT) condensation of substituted benzaldehydes and methods were used to study the tautomers of barbituric acid.18-19 Jursic20 performed the barbituric acid in the gas phase and in a polar condensation of barbituric acid substituted medium, this method was concluded that the benzaldehydes in excess of methanol solution triketo form of barbituric acid is found to be the without adding any external acid or base most stable form in the gas phase and in catalyst. Uncatalysed Knoevenagel condensation solution. Tautomers, which are partially, of barbituric acid and substituted benzaldehydes enolized forms, have higher dipolemoments in in aqueous medium at room temperature was gas phase are stabilized in polar medium.31 reported by Mohit L. et al. 21 Solvent-free 2.5 Spectral studies on Barbituric acid 90 International Journal of Current Research and Review www.ijcrr.com Vol. 04 issue 07 April 2012 UV-Vis, IR spectra, Raman spectroscopy, NMR atoms of the acid act as hydrogen donors to two and Mass spectrometry details for BA discussed oxygen atoms, each from a different molecule of by Jacek T. Bojarski et.al.32 (1,4)-dioxane.33 (Fig.3.) Maria Victoria Roux et 2.6 X-ray studies al. reported the calorimetric, computational, and Crystallographic data show that barbiturates powder Crystallographic Study of barbituric acid generally have low symmetric crystal systems, 34 and Single crystal X-ray Crystallographic i.e., monoclinic or sometimes triclinic. Sadad study has been done for the compound Al-Saqqar et al. reported the X-ray 5,5dimethyl Barbituirc acid.35 Crystallization of diffractometric analysis of barbituric acid (1,4)- Polymorphs of Phenobarbital was reported by dioxane solvate confirmed the two nitrogen Neslihan Zencirci et al.36 Fig. 3 Mechanically Induced Phase Change in differential scanning calorimetry (DSC) study of Barbituric acid was achieved by Michele R. some of the barbituric acid derivatives.38 Chierotti, et al. By grinding a commercial Electron paramagnetic resonance study of sample of barbituric acid in its trioxo form thermal decomposition of barbituric acid can be (polymorph II, 99%) for 24 h, a new compound studied by J. N. Herak et al. the structures of the has been isolated. The new phase has been detected radicals in the decomposition of the identified as the trihydroxyl isomer. barbituric acid derivatives suggest that there are 2.7 Thermogravimetric analysis and various ways of decomposition of these Thermophysical Study substances. In all the analyzed compounds a loss According to Alexandre Berlin et al. made of the substituent group R1 or R2 is detected. The thermogravimetric characteristics of barbituric loss of R1 or R2 is not necessarily decomposition acid and its derivatives they indicates the for all the molecules other competitive degrees of hydration as well as the range of decomposition pathways are possible. These stabilities of the anhydrous compounds. The experiments undoubtedly prove that in thermal decomposition of barbital has also been made to decomposition of molecules free radicals may be study the effect of alkyl substituent‘s in the 5 found.39 position on the decomposition. The differential 4 Dyes thermal analysis for dilituric acid showed a Many Barbituric acid derivatives such as sharp exotherm at 190o indicating a violent Thiobarbituric acid and its derivatives also been explosion.37 Manuel Temprado et al. reports a used in the synthesis of dyes and pigments or 91 International Journal of Current Research and Review www.ijcrr.com Vol. 04 issue 07 April 2012 intermediates in the preparation of Dyes.40,41 colourants for plastic and paint and the results of Barbituric acid has been used as disperse dyes lightfastness, heatfastness and contact bleed tests with strong fluorescent and as yellow organic are reported by D. Thetford et al. results suggest pigments,5and investigated as stain developers that only the barbiturate pigments with large for the identification of nucleic acids.42 Isidor aromatic moieties such as the pyren-1-yl and greenwald investigated that by the addition of fluoren-2-yl substituent‘s have good alcohol to a mixture of solutions of barbituric lightfastness properties at reduced shades in acid, picric acid and sodium hydroxide, a red plastics.5 Novel heterocyclic disazo barbituric precipitate is obtained.43 The barbituric acid acid dyes were synthesized and solvatochromic group present in the yellow and orange iso properties were studied (Fig.4. & Fig.5.) The indolinone and azo pigments provides hydrogen effects of varying the pH and solvent on the bonding within these pigment systems giving absorption of the dyes substituted with electron- them good durability but this still falls short of withdrawing and electron-donating groups at the standard required for automotive quality. their o-, m-, and p-position were examined in The synthesis, characterisation and properties of detail.44 Some other literature reports also well some polycyclic barbiturate pigments are documented about the dyes properties of the described. The pigments have been tested as barbituric acid.45-47 H O N HO N H N H O N O N O NH N N N H N O Fig.4 Fig.5 5 Biological Activities of Barbituric acid acetylcholine (nAChR) or BK channel receptors Barbiturates are 6-oxo derivatives of uracil, a which are all ligand-gated ion channels,49 the component of the nucleic acids.
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