Barbituric acid and derivatives

In the Diels-Alder reaction with inverse electron demand, the overlap of the LUMO of the 1-oxa-l,3-butadiene with the HOMO of the dienophile is dominant. Since the electron-withdrawing group at the oxabutadiene at the 3-position lowers its LUMO dramatically, the cycloaddition as well as the condensation usually take place at room or slightly elevated temperature. There is actually no restriction for the aldehydes. Thus, aromatic, heteroaromatic, saturated aliphatic and unsaturated aliphatic aldehydes may be used. For example, a-oxocarbocylic esters or 1,2-dike-tones for instance have been employed as ketones. Furthermore, 1,3-dicarbonyl compounds cyclic and acyclic substances such as Meldmm s acid, barbituric acid and derivates, coumarins, any type of cycloalkane-1,3-dione, (1-ketoesters, and 1,3-diones as well as their phosphorus, nitrogen and sulfur analogues, can also be ap-... 

Barbituric acid and derivatives resemble uracils in their preference for... 

Alkaloids and salts Anesthetics, in bulk form Antibiotics bulk uncompounded Atropine and derivatives Barbituric acid and derivatives bulk, uncompounded Botanical products, medicinal ground, graded, and milled Brucine and derivatives Caffeine and derivatives Chemicals, medicinal organic and inorganic— bulk, uncompounded Cinchona and derivatives Cocaine and derivatives Codeine and derivatives Digitoxin... 

It is the parent substance of a group of compounds which includes cytosine, thymine and uracil, which are constituents of nucleic acids and barbituric acid and its derivatives, which are important medicinally. 

Barbituric acid and 2-thiobarbituric acid are readily prepared by the condensation of diethylmalonate with urea and thiourea respectively, in the presence of sodium ethoxide. The use of substituted derivatives of urea and thiourea and of diethyl malonate will clearly lead to a wide range of barbituric and thiobarbituric acids having substituents in the i, 3, or 5 positions. 

The rather low values for the methylene groups of barbituric acid and its 2-thio derivative indicated a particularly easy adduct formation (84) which proceeds in water in excellent yield. 

Early investigators adduced various kinds of chemical evidence in support of a monohydroxy-dioxo structure for barbituric acid (112) (a) reaction with diazomethane afforded a mono-O-methyl deriva- iye,i59,i6o barbituric acid and its 5-alkyl derivatives are much stronger acids than the 5,5-dialkyl derivatives, and (c) the 5-bromo and 5,5-dibromo derivatives have different chemical properties. - The early physical evidence also appeared to substantiate the monoenol structure, this formulation having been suggested for barbituric acid in 1926 on the basis of its ultraviolet spectrum and again in 1934, In the 1940 s, ultraviolet spectroscopic studies led to the suggestion of other monohydroxy and dihydroxy structures for barbituric acid, whereas its monoanion was assigned structure 113 (a clear distinction between ionization and tautomerism was not made in these papers). 

Barbiturates are derivatives of barbituric acid and are synthesized by condensation of malonic acid derivatives with urea derivatives. 

Under analogous conditions, the 3-cyanomethylene-2-indolones 213 react with barbituric acid and its derivatives 191 with the formation of spiro-annulated pyranopyrimidines 223 (88JIC202, 90H(31)31)... 

Tatsumi K, Fukushima M, Shirasaka T et al. Inhibitory effects of pyrimidine, barbituric acid, and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res 1987 78 ... 

S. Dilli and D. N. Pillai, Relative electron capture response of the 2-chloroethyl derivatives of some barbituric acids and anticonvulsant drugs, J. Chromatogr., 737 111 (1977). 

Barbiturates are sedative drugs that are derived from barbituric acid and have the ability to depress the central nervous system and act especially on the sleep center in the brain, thus their sedative and sometimes hypnotic effects. 

A detailed study of the fragmentation of a series of barbituric acids and their 5-fluoro derivatives has been carried out by means of El as well as positive and negative FAB mass spectrometry219. It was proposed that the presence of a fluorine substituent induces ring opening at a different position from that observed with the nonfluorinated analogues, as outlined in Scheme 31. 

Franssen MCR, van der Plas HC (1987) The chlorination of barbituric acid and some of its derivatives by chloroperoxidase. Bioorg Chem 15 59-70... 

The complex between melamine and cyanuric acid (1 1) was reported in the literature in the late 1970s, but it was only in the early 1990s that the contributions from Whitesides and the concept of self-assembly popularized these systems [45]. Whitesides and co-workers reported the formation of tapes (Fig. 11.11), crinkled tapes and cyclic hexamers (rosettes) formed between barbituric acid and N,N -bis(p-substituted phenyl)melamine [46], In this they effectively blocked one face of melamine and, by manipulating substituents at the para position, different structures were obtained. Whiteside s putative suggestion that melamine/cyanuric acid formed an extended array (Fig. 11.12) was confirmed recently by Rao et al. with the crystal structure [47]. Hamilton and coworkers reported the crystal structure of a 5-substituted isophthalic acid derivative, which forms a cyclic aggregate held together with six pairs of hydrogen bonds, which in a way resembles the trimesic acid (Fig. 11.13) [48]. 

The approach to the interpretation of the infra-red spectrum of an unknown drug is illustrated by reference to the barbiturates. These are derivatives of malonylurea (barbituric acid) and all of them have two substituents at position 5. In addition, some of them are also substituted at position 1 and in others the oxygen atom attached to position 2 is replaced by sulphur to form thiobarbiturates. 

The barbiturates are derivatives of barbituric acid and have the general structure given below. The nitrogen atom at position 1 may be methylated. Substitution of sulphur for oxygen at position 2 gives the thiobarbiturates. 

Mokrosz J, Bojarski J. Photochemical degradation of barbituric acid derivatives. Part 3 rate constants of photolysis of barbituric acid and thiobarbituric acid derivatives. Pharmazie 1987 37(ll) 768-773. 

The tautomerism of barbituric acid and its derivatives has been briefly discussed in a review on this class of compounds (85AHC(38)229). Eleven tautomers are possible for unsubstituted barbituric acid 162. The position of the tautomeric equilibrium 162a 162b for unsubstituted barbituric acid and its N- and 5-substituted deriv-... 

The chemistry of barbituric acid and its derivatives has been studied for over 100 years if we consider 1864, the year the parent compound of this class was prepared by von Baeyer,1 as its starting point. In 1903 the therapeutic... 

The terms barbituric acid and barbiturates are used interchangeably for a general description of derivatives of 1, while the subclasses and individual compounds are named according to the mode of substitution, e.g., 5,5-dialkylbarbituric acids (2) or 5-ethyl-l-methyl-5-phenylbarbituric acid (3). 

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