Tautomers INDEX

CAS has fairly precise rules for denoting which structural systems are deemed to be tautomeric, and to which tautomer indexing is directed. In CAS nomenclature 1972-2006, tautomeric substances were often indexed under theoretical tautomers, e.g., the H- form of purines, which had no practical existence. CAS numbers for tautomeric substances therefore often referred to unknown tautomers. 

ScienceServe. 2008. Tautomer. http //www.scienceserve.com/Software/ molnet/tautomer/index.htm (accessed April 18, 2008). 

A reactivity index which accurately predicts the site selectivity of the photoisomerization of cycloheptatrienes to their bicyclic valence tautomers fails with 1//-azepines.237 For example, for methyl 2-methyl-1//-azepine-l-carboxyIatc (14), the 1-methyl isomer 16 is the predicted major product in practice the reverse is true. 

The aromaticity of 1,2,4-triazoles has been investigated and quantified using the harmonic oscillator model of aromaticity (HOMA) index, where a value of 1 is assigned to a molecule that is fully aromatic, 0 for a nonaromatic molecule, and a negative value for a molecule that is antiaromatic the data obtained were compared to other small-molecule heteroaromatics. It was determined that different tautomers of substituted and unsubstitued 1,2,4-triazoles have individual HOMA indices <2000JST(524)151>. 

Recently, a new reactivity index has been proposed (80H(14)1717> which predicts accurately the site selectivity of photocyclization of substituted cycloheptatrienes to their bicyclic valence tautomers. Unfortunately, application of the method to substituted lH-azepines is far less successful. For example, for 2-methyl-l-methoxycarbonyl-lH-azepine (37 R = 2-Me) AGrs values for C-2—C-5 and C-4—C-7 cyclization are calculated as 0.093 and 0.040 kJ mol-1, respectively, i.e. predicting the 1-methyl isomer (39) as the major product. Experimentally, however, the reverse is true, the yields being 93.5% for 3-methyl (38 R = Me) and 6.5% for 1-methyl (39 R = Me). The corresponding photoinduced valence isomerizations of 1-benzazepines to 3,4-benz-2-azabicyclo[3.2.0]hepta-3,6-dienes (38a) have been recorded (80JOC462). These isomerizations have also been achieved thermally in the presence of silver ion (80TL3403). 

The aromaticity of the different tautomers of compound 263 has been studied comprehensively by Garcia de la Vega at the density functional theory level, using double-zeta double-polarized basis sets [215], Using geometry-based index HOMA and magnetic properties-based NICS, the aromaticity of the whole rings and the different contours was evaluated. 

Sayle, R. 1999. Canonicalization and Enumeration of Tautomers, http //www.dayhght.com/meetings/emug99/ Delany/taut html/index.htm. 

Oxygen-containing heterocycles are always less aromatic than their sulfur and nitrogen counterparts, e.g., imidazole thiazole >> oxazole and pyrazole > isothiazole > isoxazole. These trends follow those of pyrrole, thiophene and furan (Section 2.3.4.2). 1,2,3-Oxadiazole is unknown and all attempts to synthesize this compound have been unsuccessful. Although it is not the least aromatic of the oxadiazoles based on the HOMA index (cf. 1,3,4-oxadiazole), its instability can be attributed to easy isomerization to the acyclic valence tautomer (i.e., 85 - 86). 

Figure 13-1. The eight most stable structures of guanine in the order or decreasing stability, with the corresponding terminology. A, Im, O and H stand for amino, imino, oxo and hydroxy (see text). The atom indexation of the purine frame is given on the first tautomer. The H atoms are not drawn...

The indexing and organisation of information relating to tautomeric or potentially tautomeric substances present severe difficulties to all information products. The issue is not how to name or document each individual tautomer, but in what assumptions to make about which structures are tautomeric, and how to organise information that may be imprecisely given in the literature under various structures, often without clear experimental data. 

A review has highlighted the roles of zwitterions in hydroxyimidazole tautomerism, for example, an aromaticity index (7 see Section 3.02.4.2.1) of 68 points to a zwitterionic species (39) rather than the hydroxy tautomer (40) which would have an value of around 79 (Equation (4)) <94H(37)249>. Thiols generally resemble the oxy analogues. Solid state IR and Raman spectroscopy point to imidazole-2-thiol existing in the SH form in the solid <89CCC2045>. 

There is some overhead in the use of indexes, constraints, triggers, etc. as discussed here. The overhead is incurred when rows are inserted or updated in the table. However, the value of this approach is that the data in the table are well validated and can be searched more reliably and efficiently. Direct lookups of canonical or stereo SMILES is simple and quick because of the index on these columns. Using the fingerprint column speeds up substructure search. Tautomers can be readily selected using the column of simple graphs. 

Chermahini et al. (2007JMST(822)33) also studied substituent effects on the aromaticity (expressed by HOMA and NICS indices) of anionic and protonated forms of C5-X tetrazole derivatives (with X = NH2, OH, OMe, SMes, H, Me, F, Cl, BH2, CF3, CN, NO, and NO2). They have shown that the stability order of protonated forms is related to the nature of the substituent. For electron-withdrawing substituents, the stability follows the sequence 1,3-H > 1,4-H > 2,3-H > 1,2-H, but in the case of electron-donating groups the order of the stabihty changes to 1,4-H > 1,3-H > 1,2-H > 2,3-H. NICS(O) values suggest that the anionic forms of tetrazoles are less aromatic than IH- tautomers, whereas the obtained NICS(l) and HOMA values indicate that the aromaticity of anionic forms lies between those found for IH- and 2H- tautomeric forms. In the case of protonated tetrazole derivatives, the most aromatic are the 2,3-H forms, whereas 1,4-H tautomers are the least aromatic. Based on the HOMA index analysis the authors concluded that the aromaticity of protonated systems can be related to the nature of the substituent. However, a closer look on their results suggests that the Tt-electron delocalization of all the studied protonated systems hardly depends on the nature of the substituent at the position C5. 

However, the thymine tautomers, with lack of correlation between HOMA index and relative energies of the tautomers, are an instructive... 

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