Thiobarbituric acid, tautomerism

The relative stabilities of tautomers of unsubstituted thiobarbituric acid were calculated using the AMI method. The oxo-thione structure 189a was found to be the most stable in the gas phase. On transition from vapor to water, the population of the most polar tautomer, the oxo(hydroxy) form, increases. However, the order of stability remains unchanged, and only for 5-halo derivatives the possibility of coexistence of two tautomeric forms in solution has been suggested (89JHC639). 

Ultraviolet speotroscopic studies with 5,5-disubstituted barbituric acids (44) indicated that in aqueous solutions, the dominant forms are either the dioxo tautomeric form (i.e., monolaotam in alkaline medium) or the trioxo tautomerio form (barbituric acid structure in acid medium). The acidity of barbiturates in aqueous solution depends on the number of substituents attached to barbituric acid. The 5,5-disubstituted barbituric acids, 5,5-disubstituted thiobarbituric acids, and 1,5,5-trisubstituted barbituric acids are relatively weak acids, and salts of these barbiturates are easily formed by treatment with bases. The pKa of 5,5-disubstituted barbituric acids ranges from 7.1 to 8.1 (44). The 5,5-disubstituted barbiturio aoids can undergo a second ionization, having pKa values in the range of 11.7 to 1 2.7. The alkali metal salts of the barbiturates coupled with their highly lipophilic character will cause chemical incompatibility reactions (precipitation) when these compounds are mixed with acid salts of weakly basic amines. 

The most popular method involves 2-thiobarbituric acid (TBA) two molecules of 2-thiobarbituric acid are condensed with malonaldehyde. The emergent chromogen — the two tautomeric structures of the red TBA-malonaldehyde adduct — is determined at 532 nm, and also often at 450 nm, to determine aUcenals and aUcanals, respectively. The qualitative Kreis test was based on a similar principle it involved detection of the epihydrine aldehyde — a tautomeric malondialdehyde — in a color reaction with resorcine or phloroglucinol. The popularity of the TBA test stems from a correlation between the results and sensory evaluations. Paradoxically, this is related to the most important drawback of the TBA technique — its lack of specificity. In addition to the reaction with malonaldehyde, TBA forms compounds of identical color with other aldehydes and ketones, products of aldehyde interaction with nitrogen compounds, and also with saccharides, ascorbic acid, creatine, creatinine, trimethylamine oxide, trimethylamine, proteins, and amino acids. For this reason, the TBA test may even be treated as a proteolysis indicator (Kolakowska and Deutry, 1983). Recently, TBA-reactive substances (TEARS) were introduced, primarily to stress that the reaction involves hydroperoxides in addition to aldehydes. Due to the nonspecificity of the TEARS test, its results reflect the rancidity of food better than other conventional methods, especially off-flavor, which is caused by volatiles from lipids as well as being affected by products of lipids interaction with nitrogenous compounds. 

Ten tautomeric forms 29a-j can be written for 2-thiobarbituric acid (Scheme 22), the properties and stabilities of which have been computed (2001CPH293, 2003SA139, 2007JPC3369). The 2-thiobarbituric acid family of crystal forms represents the richest collection of examples of tautomeric... 

Figure 3 Solid-state conversion processes between tautomeric polymorphs of 2-thiobarbituric acid.

Imines, oximes. Irradiation of 1-methylcitosine in matrix has been shown to cause amino-imino tautomerism. The related tauto-merism of 2-thiobarbituric acid has been studied both experimentally and computationally. On the reduction side, the imines has been converted into amines by visible light activation of a well defined-carbene cyclopentadienyl iron catalyst, through a general and efficient process. ... 

Mechanochemical grinding reactions are known for providing a pathway to products that are not accessible by any other procedures due to the essentially solid reaction environment. In the context of solid-state tautomerism, the mechanochemistry has recently almost become an unavoidable technique, yielding new tautomeric forms as in the case of the keto form of thiobarbituric acid [25] or the enol form of barbituric acid [78]. Milling was also used for facilitating the solid-state transformation between the solid tautomeric forms, such as the mechanochemical conversion of keto-amino tautomer of 6-[(3-hydroxy-pyridin-2-ylamino)-methylene]-cyclohexa-2,4-dienone to more stable enol form. Scheme 13.10 [45]. These examples will be discussed in more detail in the latter sections. 

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