Tautomers pattern

According to a molecular orbital calculation of Veber and Lwowski, isoindole should be favored over its tautomer, isoindolenine, by about 8 kcal/mole. However, the calculated electronic distribution is markedly different in the two oases, particularly at position 1, and it is to be expected that the nature and pattern of substituents will play an important role in determining the position of tautomeric equilibrium between these two species. 

NH forms, respectively. Although considerable work has been reported on these compounds, much of it was, or appeared to be, contradictory, and only recently has the complex pattern of the tautom-erism which occurs in this series become clear. ... 

The parent 1,4-thiazine exists exclusively as the 2H tautomer 86, independently of the medium used, as do its pyrimidino-fused derivatives 87 (76AHCS1, p. 80 84MI2). However, the equilibrium could be affected significantly by a substitution pattern in the thiazine ring, as was shown in the example of 1,4-benzothiazine. Thus, 3-phenyl-1,4-benzothiazine 88 (R = H, R = Ph) is present in aqueous hydrochloric acid as a 4 1 mixture of 2H (88a) and AH (88b) isomers... 

Tautomer conversion involves nonlocal structural editing, and substructural patterns must generally be defined more carefully. 2-Pyridones are consistently registered in the AstraZeneca database as their typically less stable 2-hydroxypyridine tautomers. The conversion can be carried out by first defining an atom type corresponding to a nonfused aromatic carbon atom. 

Interpretation of NH-tautomer visible abyrption spectra. The data summarized in Table 1 reveal that each of the NH-tautomers exhibits four visible bands which are generally characteristic of free-base porphyrins. But the observed intensity pattern dramatically changes when passing from one tautomer to another for each compound while the situation I (Qx) < I (Qy) is observed for one tautomer the spectral picture I (Qx) > i (Qy) occurs for the second one and vice versa. 

The tautomeric forms 13-15 would be responsible for a relatively strong signal at 2050 cm", characteristic for 1-lithioacetylenic moiety Eurthermore, it is hard to account for the strong and relatively broad band at 1800 cm" from either species 13 or 14. AU of the spectral features seem to iudicate the tautomeric structure 16 as the most probable, with species 15 uot fully excluded as a possibility. However, the simplicity of the spectral pattern iudicates that oue structure predominates in case of a mixture of tautomers". ... 

Pappalardo and co-workers studied the mass spectral characteristics of alkyl and aryl substituted 2,5-dithio-1,3,4-thiadiazoles. Selected ions in the mass spectra of SH, S-CH3, and S-aryl thiadiazoles were tabulated. The S-aryl thiadiazoles form stable cyclic ions yielding additional fragments. The fragmentation pattern is dependent on the structural characteristics of the substituents. If both tautomers—thiol and thione—are present, the molecular ion will also lose CS2. Besides the base peak, intense peaks observed in the MS spectrum are due to extensive fission of the thiadiazole ring. Some of the fragments formed are shown in Scheme 4 <820MS(17)335). 

Spectra of thiazetidines have been recorded by Gallow and Klaeser. The 1,3-thiazete 45 and its tautomer 46 produced the following fragmentation pattern. 

The first step of the design of stress experiments should be to examine the molecular formula of the test compound. Does the structure resemble substances for which a degradation pattern is already known Does it contain easy oxidizable functional groups Do tautomers exist, that can be more sensitive to oxidants Can pH affect the sensitivity, because prototropic equilibria can generate easily oxidizable species Are potential degradation impurities available Time spent in answering these questions and in collecting literature data is never lost. 

There are numerous other modifications of nucleobases possible, many of which are biologically relevant in that they lead to alternations in p/fa values, changes in tautomer structure as well as their base pairing patterns (55). Examples include ligands such as N6-methoxyadenine, which is a promutagen (66, 67) as well as 8-oxoadenine and 8-oxoguanine (68), which are known mutagens. 

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