Barbituric acid derivatives acids

White crystals, m.p. 191°C. A barbituric acid derivative. The sodium salt is administered orally as a sedative. 

The ZwKKER reaction involving Co salts is frequently used for the detection of barbituric acid derivatives [31-35], but some purine, pyridine and piperidine derivatives and heterocyclic sulfonamides also yield colored derivatives. The Zwkker reaction is particularly sensitive when it is possible to form a tetrahedral complex [Co(Barb)2 Xj] (X = donor ligand, e.g. amine) [4]. 

Kakemi, K. Arita, T. Hori, R. Konishi, R., Absorption and excretion of drugs. XXX. Absorption of barbituric acid derivatives from rat stomach, Chem. Pharm. Bull. 17, 1534-1539 (1967). 

An asymmetric isoindoline pigment preparation has been claimed, starting from 1,2-dicyanobenzene which is reacted in alcohol and a base, followed by addition of a cyanomethylene compound and subsequently a barbituric acid derivative, whereby all reactions are accomplished without isolation of the corresponding intermediates [22],... 

By using the same catalytic system, alkylations of 1,3-dimethylbarbituric acid with alcohols were also accomplished (Scheme 5.31) [68]. The Cp lr-catalyzed alkylation using 2-iodobenzyl alcohol, followed by palladium-catalyzed carbon-carbon bond formation with allene, gave spirocyclic barbituric acid derivatives in a one-pot process. 

It would be extremely tedious for you to read the synthesis of all the barbituric acid derivatives that exist today, so I will limit you to the more widely used and important ones. I have grouped the listed barbiturates by their clinical action and the duration of that action. 

Alkyl and 1-aralkyl-5,6-dihydrouracils (LXXIX), prepared by condensation of A -(2-carbamoylalkyl)aralkylamines with urea or by treating a suitable primary amine with an ester of acrylic acid followed by cyanic acid, are CNS depressants and anticonvulsants [639, 640], as well as anti-inflammatory agents [641]. Such compounds are to be compared with the corresponding barbituric acid derivatives in which not more than one hydrogen in the 5-position is substituted, and also with barbiturates in which the 5,5-substituents are similar to the R and groups of the 5,6-positions here. 

The barbituric acid derivative 40a-f (0.50 mmol) was ground in an agate mortar. Solid diazonium salt289j (0.50 mmol) was added and coground in five portions for 5 min each. Most of the diazonium band at 2280 cm had disappeared, but completion of the reaction was achieved by 24 h ultrasound application in a test tube. After neutralization (0.5 N NaOH, 20 mL), washing (H2O), and... 

Cyclic thioureas such as 2-thiouracil 1118 (R = H), its 6-methyl 1118 (R = Me) and 6-propyl derivatives 1118 (R = Pr), as well as thiobarbital 1119 are effective agents against hyperthyroidism, while thiamylal 1120 is used as an anesthetic. A large number of barbituric acid derivatives have hypnotic or sedative effects, and allobarbital 1121 (R = R = allyl), aprobarbital 1121 (R = allyl, R = r-Pr), cyclobarbital 1121 (R = Et, R = 1-cyclohexenyl), pentobarbital 1121 (R = Et, R = 2-pentyl), phenobarbital 1121 (R = Et, R = Ph), propallyonal 1121 (R = isopropyl, R = 2-bromoallyl), and secobarbital 1121 (R = allyl, R = 2-pentyl) are all examples of N-unsubstituted barbiturates, while hexobarbital 1122 represents an N-methylated derivative. 

Rx Butalbital/aspirin/caffeine Butalgen, Fiorinal, Fiorgen, Fiormor, Fortabs, Iso-butal. Isobutyl, Isolin, Isollyl, Laniroif, Lanorinal, Marnal, Tecnal, Virbutal Rx Butalbital/aspirin/caffeine wifh codeine Ascomp with Codeine No3, Butalbital Compound with Codeine, Butinal with Codeine NoB, Fiorinal with Codeine NoB, Idenal with Codeine, Isollyl with Codeine Chemical Class Barbituric acid derivative... 

The utility of barbituric acid derivatives as sedative-hypnotic agents is discussed in more detail later in this chapter. Studies on the chemical simplification of these pyrimidinetrione derivatives led to the discovery that pyridinediones, or glutarimides,... 

Polymeric barbituric acid derivatives, (III), prepared by Kishioka et al. (3) were effective as antireflective coatings for semiconductors. 

Extended Adjacency Matrix-Kow Relationships Yang et al. [39] derived two descriptors, EAS and EAmax, from the extended adjacency (EA) matrix and demonstrated their correlation with log,0 ow for barbiturate acid derivatives with structures I and II ... 

The uses of constant-current coulometry for the determination of drugs in biological fluids are few, basically due to sensitivity restriction. Monforte and Purdy [46] have reported an assay for two allylic barbituric acid derivatives, sodium seconal and sodium sandoptal, with electrogenerated bromine as the titrant and biamperometry for endpoint detection. Quantitative bromination required an excess of bromine hence back titration with standard arsenite was performed. The assay required the formation of a protein-free filtrate of serum with tungstic acid, extraction into chloroform, and sample cleanup by back extraction, followed by coulometric titration with electrogenerated bromine. The protein precipitation step resulted in losses of compound due to coprecipitation. The recoveries of sodium seconal and sodium sandoptal carried through the serum assay were approximately 81 and 88%, respectively. Samples in the concentration range 7.5-50 pg/mL serum were analyzed by this procedure. 

Amobarbital is a barbituric acid derivative of intermediate duration of action. It is administered orally in doses of 15 to 200 mg as a sedative hypnotic and in ampoules of 65 to 500 mg for intravenous and intramuscular injection for the seizure control.6 Following a single oral dose of 120 mg, peak serum concentrations averaged 1.8 mg/L after 2 h.7 After an oral dose of 600 mg distributed over a 3-h period, the peak blood concentration was achieved after 30 min, averaging 8.7 mg/L, with a decline to 4.1 mg/L by 18 h.6... 

Triaminopyrimidine and barbituric acid derivatives are complementary components presenting the required features, since they should be able to form two arrays of three hydrogen bonds with each other. However, as pointed out above, based solely on hydrogen bonding recognition, their association could yield either a linear or a macrocyclic supramolecular structure (Section 9.4.2 Figure 37). 

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