Substitution in barbituric acids

Aromatic and aliphatic aldehydes readily condense with thiobarbituric acid to form 5-arylidenethiobarbituric acids or 5-arylidenebis(thiobarbituric acid)s. A longer time is required for condensation with ketones. The UV spectra of the arylidene derivatives have two absorption bands, with maxima at 240–275 and 280–405 nm, while the spectra of the alkylidene derivatives only one absorption band, with a maximum at 280–295 nm.For part I, see [1].     

Polymorphism in substituted barbituric acids

Of twenty substituted barbituric and thiobarbituric acids studied, nine have been found to exist in polymorphic forms. These are barbital, butethal, amobarbital, pentobarbital, thiopental, phenobarbital, aprobarbital, nostal and kemithal. The different modifications have been studied by X-ray diffraction and infra-red spectrophotometry, and the transition temperature ranges have been determined. The forms found are divided into two groups on the basis of their infra-red spectra. The tautomeric form of the compounds in the solid state is discussed briefly.     

Addition of barbituric acids to benzoylcyanamide

Derivatives of 5-diaminomethylenepyrimidine-2,4,6-trione were synthesized by adding barbituric andN,N′-dicyclohexylbarbituric acids to benzoylcyanamide in the presence of stoichiometric amounts of Ni(OAc)₂. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1701–1703, September, 1997.     

Tautomerism in barbituric and thiobarbituric acids

The molecular geometry of barbituric and thiobarbituric acid tautomers have been fully optimized using the AMI method in order to estimate the relative energies of the tautomers. The results are in agreement with available experimental data and indicate that in the vapour the barbiturate ring is essentially planar. In both unsubstituted compounds the trioxo structure is found to be the most stable one, in agreement with experimental findings in the solid. Tautomeric equilibria are sensitive to phase change and to substitution at the C₅ position. On passing from the vapour to the water the population of the most polar structure increases, although the order of stability remains unchanged and only for the Br and I derivatives it can be suggested the coexistence of two forms in solution. The substitution at C₅ does not alter the order of stability except for the 5-nitro derivatives where the dioxo form predominates, in agreement with experimental results in the solid. Electron affinities and ionization potentials of the tautomers have been evaluated and briefly discussed. It is suggested that gas-phase uv photoelectron spectroscopy should be able in analysing the tautomeric equilibria of barbituric and thiobarbituric acids in the vapour.     

Novel codeinone derivatives via Michael addition of barbituric acids

Two novel adducts of codeinone with barbituric and 2-thiobarbituric acids have been synthesized via Michael addition. The compounds were spectroscopically elucidated by means of IR-LD spectroscopy of oriented samples as a suspension in nematic liquid crystals, UV spectroscopy and ¹H and ¹³C NMR spectroscopy. The 2-thiobarbituric adduct was characterized by X-ray crystallography. HPLC tandem mass spectrometry (HPLC ESI MS/MS) and thermal methods were also employed. Quantum chemical calculations have been performed with a view to obtaining the electronic structure and vibrational properties of the novel compounds.     

5-Fluoro-4-alkyl(aryl)barbituric acids

Fluorobarbituric acids are formed as a result of the reaction of 5-alkyl(aryl)barbituric acid salts with perchloryl fluoride.     

15N-NMR-studies on the neutralization reaction of arylidene dimethyl barbituric acids organicLewis acids 38

The¹⁵N-NMR-spectra of benzylideneN,N-dimethyl barbituric acid andp-chloro-benzylideneN,N-dimethyl barbituric acid have been measured together with their addition products with piperidine and morpholine. TheLewis Acid reactivity is discussed in terms of¹⁵N-chemical shifts.Die¹⁵N-NMR-Spektren von Benzyliden-N,N-dimethylbarbitursäure undp-Chlorbenzyliden-N,N-dimethylbarbitursäure und deren Additionsprodukte mit Piperidin und Morpholin wurden gemessen und im Hinblick auf dieLewissäureaktivität dieser Substanzklasse interpretiert.

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¹⁵N-NMR-Untersuchungen über die Neutralisierungsreaktion von Arylidendimethylbarbitursäuren. OrganischeLewis-Säuren 38

     

Kharasch reaction: Cu-catalyzed and non-Kharasch metal-free peroxidation of barbituric acids

It was discovered that the Kharasch peroxidation of barbituric acids proceeds both with a Cu-catalyst and without a metal catalyst. Despite the presence of possible thermal-initiated side oxidation pathways, α-tert-butylperoxybarbiturates were selectively prepared from substituted barbituric acids and tert-butyl hydroperoxide.     

Electron-capture gas chromatography of barbituric acids and diphenylhydantoin after pentafluorobenzylation.

Alkylation of barbituric acids and diphenylhydantoin with pentafluorobenzyl bromide is described; the reaction is quantitative in the presence of excess of triethylamine. The electron-capture detector response of the derivatives is high, ranging from 2 to 8 x 10(-17) moles/sec. The derivatives demonstrate excellent peak symmetry and are well suited to quantitative analysis. The structures of the derivatives have been confirmed by mass spectrometry.     

Reaction of 4-acylaminomethylpyridine N-oxides with 5-monosubstituted barbituric acids in presence of acetic anhydride

The 5-alkyl-5-[(3,5-dimethylbenzoylamino)(4-pyridyl)methyl]barbituric acids are obtained in the title reactions, but they fail when barbituric or 5-phenylbarbituric acids are used. These results are explained by the pK_a values of barbituric acids.     

Interaction of nucleic acids with the glycocalyx

Mammalian cells resist the uptake of nucleic acids. The lipid bilayer of the plasma membrane presents one barrier. Here, we report on a second physicochemical barrier for uptake. To create a sensitive probe for nucleic acid-cell interactions, we synthesized fluorescent conjugates in which lipids are linked to DNA oligonucleotides. We found that these conjugates incorporate readily into the plasma membrane but are not retained there. Expulsion of lipid-oligonucleotide conjugates from the plasma membrane increases with oligonucleotide length. Conversely, the incorporation of conjugates increases markedly in cells that lack the major anionic components of the glycocalyx, sialic acid and glycosaminoglycans, and in cells that had incorporated highly cationic lipids into their plasma membrane. We conclude that anionic oligosaccharides provide a formidable barrier to the uptake of nucleic acids by mammalian cells. This conclusion has implications for genomic stability, as well as the delivery of genes and siRNAs into mammalian cells.     

Condensation of al-sugars with barbituric acid

Al-D-glucose and al-D-galactose pentaacetates and al-D-mannose heptaacetate are condensed with barbituric acid in 10% acetic acid to give a bis-product I, while in ethanol, water, and 50% ethanol, a mono-product I is formed.     

Interaction of non-ionic hydrogels with weak aromatic acids

Measurements are reported of the swelling behaviour at 20°C of poly (N isopropylacrylamide) (PNIPA) gels in aqueous solutions of two weak aromatic acids, phenol and resorcinol. For solute concentrations below 45 mmol/l the uptake of these solutions is similar. Due to selective solvation phenol exhibits an excess equilibrium concentration inside the gel of 5% over that in the surrounding bath, while for resorcinol, the excess is found to be 12%. At 50 mmol/l solute concentration, both systems display a volume transition accompanied by expulsion of the solvent. The solubility limits in water of these aromatic compounds, which are significantly different from each other (870 mmol/l and 9080 mmol/l respectively), are far above this critical concentration. In the collapsed condition the expelled liquid spreads on the surface of the phenol treated gel, while an ordered arrangement of separate droplets is generated in the case of resorcinol. In the latter case an acute contact angle was observed. It is also shown by acid-base titration that the PNIPA/water system may exhibit a slight ion exchanging character.