Barbituric acids, halogenation

Other methods for the determination of chlorine in seawater or saline waters are based on the use of barbituric acid [13] and on the use of residual chlorine electrodes [ 14] or amperometric membrane probes [15,16]. In the barbituric acid method [12], chlorine reacts rapidly in the presence of bromide and has completely disappeared after 1 minute. This result, which was verified in the range pH 7.5-9.4, proves the absence of free chlorine in seawater. A study of the colorimetric deterioration of free halogens by the diethylparaphenylene-diamine technique shows that the titration curve of the compound obtained is more like the bromine curve than that of chlorine. The author suggests... 

Halogenation of diazines containing one or more activating groups proceeds easily (Br2 or Cl2 in H20, AcOH, or CHC13, 20-100°C). Sometimes 5,5-dihalo products are formed by ring dearomatization, e.g. barbituric acid (107) gives successively (108) and (109). 

Searching for other 6-membered "diazido malonyl N-heterocycles" we have selected the pyridazine derivative 25 and diazido barbituric acids 32 as model systems, since they are available easily and in large quantities. Compound 25 is obtained in the usual way by chlorination of 23 with sulfuryl chloride and exchange of the halogen atoms with sodium azide. 

Derivatives of barbituric acid (10.28) are so reactive in the presence of halogens that it is often difficult to obtain the 5-monohalogenated derivatives [21CB1035 22CB3400 74JCS(P1)2095 79JOU357], 5,5-dihalo compounds being obtained. Fluorination of 5-substituted barbiturates with perchloryl fluoride was shown to be first order in each component. Elec-... 

As the number of carbon atoms at the fifth carbon position increases, the lipophilic character of the substituted barbituric acids also increases (44). Branching, unsaturation, replacement of alicyclic or aromatic substituents for alkyl substituents, and introduction of halogen into the alkyl substituents all increase the lipid solubility of the barbituric acid derivatives. A limit is reached, however, because as the lipophilic character increases, the hydrophilic character decreases. Although lipophilic character determines the ability of compounds to cross the blood-brain barrier, hydrophilic character also is important, because it determines solubility in biological fluids and ensures that the compound reaches the blood-brain barrier. Introduction of polar groups into the alkyl substituent decreases lipid solubility below desirable levels. Modifications at this position by variation of the alkyl substituents were of primary importance in the development of barbiturates with short (3-4 hours) to intermediate (6-8 hours) duration of action. These barbiturates were once extensively used as sedatives and hypnotics. 

Trace amounts of cyanide are usually determined by flow injection spectrophotometric procedures. The target species is first halogenated with chlora-mine-T, after which it reacts with a mixture of pyrazolone or barbituric acid and isonicotinic acid or pyridine to form a bluish-violet polymethine dye. The implementation of gas-diffusion modules in the flow setup for hydrogen cyanide separation avoids matrix interferences and enables the adaptation of inherently nonselective detectors, such as metallic silver-wire electrodes for potentiometric measurements. Total inorganic cyanide, including free and complexed species, such as iron-cyanide complexes, may be determined by sample decomposition with UV irradiation and further photometric or amperometric analysis. 

Depressants may be hydrocarbons, halogenated hydrocarbons, alcohols, ethers, ketones, weak acids (like the barbiturates), weak bases, or sulphones. They are the selectively toxic agents used in medicine as hypnotics and general anaesthetics. This is the only kind of biological activity in which structure simply does not matter (there is much more about this in Chapter 15). See Section 3.3 for the general function of partition effects in securing selective distribution of drugs. 

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