Tautomer definition

The last example is somewhat more complicated since four isomers (two tautomers and two conformations) are present at equilibrium (Figure 9) (78BSB189). The experimental value (3.73 D, Table 3) establishes the predominance of the 3-azido tautomer but does not allow the determination of the conformational equilibrium other methods (Section 4.04.2.3.4(v)) are necessary to establish definitely the Z conformation (43b). 

Interconversion between two tautomeric structures can occur via discrete cationic or anionic intermediates (scheme 24, where T is an anion capable of reacting with a proton at a minimum of two distinct sites). Alternatively, interconversion can occur by simultaneous loss and gain of different protons (scheme 25, w here T has the same definition as in scheme 24). These mechanisms are well established for acyclic compounds, but they have been much less thoroughly investigated for heteroaromatic systems. The rate of interconversion of two tautomers is greatest when both of the alternative atoms to which the mobile proton can be attached arc hetero atoms, and isolation of the separate isomers is usually impossible in this case. If one of the alternative atoms involved in the tautomerization is carbon, the rate of interconversion is somewhat slower, but still fast. When both of the atoms in question are carbon, however, interconversion is... 

No definite experiments have been carried out with regard to the relative stability of the tautomers of 2-substituted indazolones 111. On the basis of basicity arguments, (he hydroxy tautomer 111a was considered to be preferred [96JCS(P2)2263],... 

Recently a definitive study of several isoxazol-5-ones using infrared and ultraviolet spectroscopy (Table I) has shown that the balance between the various tautomers is a delicate one and that all three of the structural types can predominate depending upon the nature of the substituents and the conditions of the experiment. However, the hydroxy form is only found when it is stabilized by chelation (i.e., a carbonyl substituent in the 4-position). The other compounds exist in the CH form in nonpolar media increasing polarity of the solvent stabilizes increasing amounts of the more polar NH forms. 

Compound 6 crystallizes from cyclohexane as colorless needles which have no definite melting point there is a change of color to yellow at 128-134 C and the compound then melts sharply at 187-189 r C. When the colorless form is kept for a long time or recrystallized from pyridine or dimethyl sulfoxide it is changed into the yellow modification of mp 187-189 C recrystallization from cyclohexane reverses the process. It has been suggested that the yellow stable form has structure 6A and that the colorless metastable compound is the tautomer 2-methyl-l//-pyrido[2,3-6][l, 4]diazepin-4(5//)-one (6B). There is evidence from 1H NMR spectroscopy that the isomeric pyridodiazepin-2-one, yellow crystals, mp 195—197 " C, exists as an inseparable mixture of the tautomers 4-methyl-l//-pyrido[2,3-6][l,4]diazepin-2(3//)-one (7 A) and 4-methyl-l H-pyrido[2,3-6][l, 4Jdiazepin-2(5//)-one (7B) in the ratio 1 3. 

The transformation used above to enumerate tautomers would lead to identical products when applied to symmetrically substituted pyrazoles. The set of structures generated in the enumeration process is converted to a sorted list of canonical SMILES [23] from which duplicates are easily eliminated. Structures registered in alternative tautomeric forms are converted to identical lists of SMILES that can each be represented by their common first member. This effectively extends the definition of canonical SMILES to cover an ensemble of tautomeric forms and makes it possible to check for duplicate structures without having to register multiple forms [16, 26]. 

Our current ionization and tautomer model encodes biased and balanced equilibria with 108 and 35 rules respectively. Extensive use is made of atom typing to specify chemistry in as generic a manner as possible, which reduces the number of rules required, for example, a number of heteroaromatic nitrogen types, including selected 2-aminopyridines and imidazoles, are aggregated into a definition of bases with pK ... 

The NH-tautomer structure. The solution of the question of internal protons location in each tautomer of the investigated porphyrins with non-symmetrical substitution will result in obtaining definite correlations between tautomer spectra and their structures. Here we present such information for compound 10. 

Quinone oximes and nitrosoarenols are related as tautomers, i.e. by the transfer of a proton from an oxygen at one end of the molecule to that at the other (equation 37). While both members of a given pair of so-related isomers can be discussed separately (see, e.g., our earlier reviews on nitroso compounds and phenols ) there are no calorimetric measurements on the two forms separately and so discussions have admittedly been inclusive—or very often sometimes, evasive—as to the proper description of these compounds. Indeed, while quantitative discussions of tautomer stabilities have been conducted for condensed phase and gaseous acetylacetone and ethyl acetoacetate, there are no definitive studies for any pair of quinone oximes and nitrosoarenols. In any case. Table 4 summarizes the enthalpy of formation data for these pairs of species. 

It has been reported that the UV spectra of l,2,3-benzotriazin-4(3/f)-one (10, R = H), the corresponding triazinethione (39, R = H) and the 4-alkylamino-l,2,3-benzotriazines (56) formed by treatment of 39, R = H, with alkylamines are nearly identical, and this has been taken as evidence that the compounds 56 actually exist as the 3,4-dihydro-4-imino tautomers. This claim has not, however, been substantiated, and, in the absence of more definitive evidence, structure 56 is almost certainly the more accurate representation for these compounds. 

In general, the problem of tautomerism in nucleic acid bases has been approached by comparing the IR spectra of several isoelectronic model compounds. The model corresponding to the cytosine tautomers 4 or 5 have not yet been investigated. The IR spectroscopy studies cannot therefore definitely rule out these tautomers. It seems, however, that they do rule out form 6 for cytosine and cytidine and indicate that the dominant tautomer of the compounds in aqueous solution is the lactam-amino form 2, and that the protonated cations have the structure 7. 

In spite of the fact that numerous oxidation reactions are known, that lead to a-functionalization of ketones [159,160], in most cases enol radical cations are not involved in these transformations, and rigorous evidence for their formation through selective oxidation of the enol tautomer (Fig. 2, path 2) has only been obtained in a few cases. For example, it could be inferred from kinetic studies that in many cases enols are not intermediates in aqueous oxidation reactions with V(V), Co(III), Ce(IV) and Mn(III) [161-163], whereas in acetic acid Mn(III) was postulated to attack the enol form of ketones [164,165], but not by electron transfer [166]. On the other hand, oxidants as Cr(VI), Tl(III), Hg(II) and Mn(VII) [167] as well as Pb(IV) [168] definitely react with the enol form, but since with these inner-sphere oxidants electron transfer is assumed to occur in a bonded fashion, radical cation intermediates are most likely not implicated. 

Studies of the aminoimidazolinones have also been limited. However, in the 1-substituted 2-aminoimidazoIin-4-ones the NMR evidence that C-5 is close to sp in nature limits the possible tautomers to three (89-91), with the third (91) not being at all likely (Scheme 29). Of the other two, the available evidence is equivocal, but the pi a of 4.55. 80 rules out (90) (expected pi a 8-9) leaving the probable form as the amino-oxo structure (89). Similar evidence for 2-amino-l-methylimidazolin-5-ones, while not definitive, suggests that both amino and imino forms have significant contributions to the equilibrium. The added complication in unsubstituted 2-aminoimidazolin-4(5)-ones of annular tautomerism increases the number of possible tautomeric forms (Scheme 30). The UV absorption in ethanol at 213-225 nm, pK of 4.5-4.8 and NMR spectrum showing an sp -type C-5 still leave five possible structures, and the problem is as yet unresolved. The distinction between 4-amino and 4-imino forms in 4-aminoimidazolin-2-ones has also not been made. 

Differentiation of tautomers by the use of UV spectra has not been too rewarding. Thus whereas hypoxanthine almost certainly exists as the lactam form (13) as indicated by IR and other spectral studies, its UV absorption spectrum (Amax 249 nm, pH 5.6) is similar to that of 6-methoxypurine (Amax 252 nm, pH 5.2), a derivative of the lactim form of hypoxanthine, and l,7-dimethyl-6-oxo-l(if),6(if)-purine (43) (B-73MI40902), a definite lactam derivative. On the other hand, the UV spectrum of 8-oxo-7(H),8(/7)-purine (44) is closer to that of its 7- and 9-monomethyl and 7,9-dimethyl (oxo or lactam) derivatives than to 8-methoxypurine (45) (B-73MI40902) implying the oxo structure. Even in basic solutions where the lactim structure is expected, the results may be difficult to interpret. Thus the spectrum of the anion of hypoxanthine is similar to that of the neutral species of adenine, (Amax 258 and 260 nm, respectively) whereas this is not true of the 2- and 8-oxopurines when compared with the corresponding aminopurines. 

Azole Definition of Kt Conclusion Tautomer with highest IX Less basic... 

Deduplication. When registering into a chemical structure database, the process of finding whether the given structure already exists in the database. This usually involves performing an exact match search with the given structure as the search query. Note that the definition of exact match may vary with the database, and it may even be configurable. For example, some databases may consider tautomers to be acceptable as exact matches, whereas others may require a more strict definition. 

H atom addition, protonation state, active site definition, His tautomers, structural water, pharmacophore definition etc. 

---