TAUTOMER Molecular

Solid state NMR studies of l,3-imidazolidine-2-thione, I,3-imidazolidine-2-selenone and some of their iV-substituted derivatives have been reported. Spinning sidebands of thione and selenone carbons were analysed to yield chemical shift anisotropies for these carbons. The NMR spectrum of imidazolidine-2-thione showed some evidence for the presence of thiol tautomer. Molecular computations were carried out for imidazolidine-2-thione and its iV-methyl derivative to yield relative energies of various possible tautomers. 

Acyl-, 4-alkoxycarbonyl- and 4-phenylazo-pyrazolin-5-ones present the possibility of a fourth tautomer with an exocyclic double bond and a chelated structure. The molecular structure of (138) has been determined by X-ray crystallography (Table 5). It was shown that the hydroxy group participates in an intramolecular hydrogen bond with the carbonyl oxygen atom of the ethoxycarbonyl group at position 4 (8OCSCII21). On the other hand, the fourth isomer is the most stable in 4-phenylazopyrazolones (139), a chelated phenyl-hydrazone structure. 

Repeat your analysis for tautomeric equilibria between 4-hydroxypyridine and 4-pyridone, 2-hydroxypyrimidine and 2-pyrimidone and 4-hydroxypyrimidine and 4-pyrimidone. For each, identify the favored (lower-energy) tautomer, and then use equation (1) to calculate the ratio of tautomers present at equilibrium. Point out any major differences among the four systems and rationalize what you observe. (Hint Compare dipole moments and electrostatic potential maps of the two pyridones and the two pyrimidones. How are these related to molecular stability )... 

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. 

Two independent molecular orbital calculations (HMO method) of delocalization energies for isoindole and isoindolenine tautomers agree that the isoindole form should possess the more resonance stabilization. The actual difference calculated for isoindole-isoindolenine is about 8 kcal/mole, but increases in favor of the isoindole with phenyl substitution at position 1 (Table VI).Since isoindole and isoindolenine tautomers have roughly comparable thermodynamic stabilities, the tautomeric proce.ss is readily obser-... 

Contributions in this section are important because they provide structural information (geometries, dipole moments, and rotational constants) of individual tautomers in the gas phase. The molecular structure and tautomer equilibrium of 1,2,3-triazole (20) has been determined by MW spectroscopy [88ACSA(A)500].This case is paradigmatic since it illustrates one of the limitations of this technique the sensitivity depends on the dipole moment and compounds without a permanent dipole are invisible for MW. In the case of 1,2,3-triazole, the dipole moments are 4.38 and 0.218 D for 20b and 20a, respectively. Hence the signals for 20a are very weak. Nevertheless, the relative abundance of the tautomers, estimated from intensity measurements, is 20b/20a 1 1000 at room temperature. The structural refinement of 20a was carried out based upon the electron diffraction data (Section V,D,4). 

The crystal structure analysis of the parent 1,2,3-triazole in the solid state unambiguously demonstrated that it crystallizes as a 1 1 molecular complex of both possible tautomers 24a and 24b, linked by a N-H - N hydrogen bond [97AX(C)1846]. 

Molecular orbital theory indicates that there is little difference between the stability of the two tautomers of purine, 42 and 43. Molecular orbital calculations indicate that purine forms a monocation by protonation at N-3 or at A precise X-ray crystal-... 

Three decades ago the preparation of oxepin represented a considerable synthetic challenge. The theoretical impetus for these efforts was the consideration that oxepin can be regarded as an analog of cyclooctatetraene in the same sense that furan is an analog of benzene. The possibility of such an electronic relationship was supported by molecular orbital calculations suggesting that oxepin might possess a certain amount of aromatic character, despite the fact that it appears to violate the [4n + 2] requirement for aromaticity. By analogy with the closely related cycloheptatriene/norcaradiene system, it was also postulated that oxepin represents a valence tautomer of benzene oxide. Other isomers of oxepin are 7-oxanorbornadiene and 3-oxaquadricyclane.1 Both have been shown to isomerize to oxepin and benzene oxide, respectively (see Section 1.1.2.1.). 

Tautomers are defined as isomers which are readily interconvertible. It is clear that the distinction between tautomerism and ordinary isomerism is very vague indeed, and that it depends on the interpretation of the adverb readily. It is customary to designate as tautomers those isomers whose half-lives (with respect to interconversion) are under ordinary circumstances less than the times required for laboratory operations to be carried out (some minutes or hours), so that the separation of the isomers from the equilibrium mixtures is difficult. The distinction between tautomers and ordinary isomers has no molecular significance whatever, since it is dependent on the accidental ordinary rate of human activity. 

Similarly, the structure of 5-nitro-2,4-dihydro-377-l,2,4-triazol-3-one (NTO) 6 has been scrutinized using molecular orbital calculations using the 6-31+G and 6-311+G basis sets. These calculations examined the various tautomers of NTO and give an insight into the molecular mechanisms involved in its explosive decomposition <1996JA8048>. 

The tautomerisation of the purine bases adenine and guanine and of the pyrimidine bases thymine, cytosine, and uracil has important implications in molecular biology, and the occurrence of rare tautomeric forms of these bases has been suggested as a possible cause of spontaneous mutagenesis (Lowdin, 1965 Pullman and Pullman, 1971 Kwiatowski and Pullman, 1975). Three of the most likely tautomers for cytosine are shown in [87]—[89], together with the less likely imino forms [90] and [91] (Scanlan and Hillier,... 

Relative contribution of each of these structures differs significantly and is determined by internal structural characteristics of the nitrones and by the influence of external factors, such as changes in polarity of solvent, formation of a hydrogen bond, and complexation and protonation. Changes in the electronic stmcture of nitrones, effected by any of these factors, which are manifested in the changes of physicochemical properties and spectral characteristics, can be explained, qualitatively, by analyzing the relative contribution of A-G structures. On the basis of a vector analysis of dipole moments of two series of nitrones (355), a quantum-chemical computation of ab initio molecular orbitals of the model nitrone CH2=N(H)0 and its tautomers, and methyl derivatives (356), it has been established that the bond in nitrones between C and N atoms is almost... 

Parchment et al. [271] have provided more recent calculations on the 3-hydroxypyrazole equilibrium at the ab initio level. They noted that tautomer 9, which was not considered by Karelson et al. [268], is the lowest-energy tautomer in the gas phase at levels of theory (including AMI) up to MP4/6-31G //HF/3-21G [271], Although 8 is the dominant tautomer observed experimentally in aqueous solution, in the gas phase 8 is predicted to be nearly 9 kcal/mol less stable than 9 at the MP4 level [271], Using a DO model with an unphysically small cavity radius of 2.5 A, Parchment et al. [271] were able to reproduce at the ab initio level the AMI-DO prediction of Karelson et al. [268], namely that 8 is the most stable tautomer in aqueous solution. With this cavity, though, 8 is predicted to be better solvated than 9 by -22.2 kcal/mol [271], This result is inconsistent with molecular dynamics simulations with explicit aqueous solvation [271], and with PCM and SCME calculations with more reasonable cavities [271] these predict that 8 is only about 3 kcal/mol better solvated than 9. In summary, the most complete models used by Parchment et al. do not lead to agreement with experiment... 

Physicochemical properties rather than reactivities were also explored. Molecular electrostatic potential (MEP) was calculated for the [l,2,4]triazolo[4,3- ]pyridine fragment 23, according to the CHELPG algorithm. This afforded a prediction of its H-bond acceptor ability in view of the synthesis of p38 MAP kinase inhibitors <2005JME5728>. Tautomerism was also examined for compound 24, also postulated as two possible acyclic structures. The ab initio self-consistent field (SCF)-calculated energies support 24a as the most stable tautomer <1999MRC493>. 

When the two wells are of similar energies, and the crystal structure allows, the above will no longer be the situation. We may then expect a number of consequences There may be a measurable displacement of the hydrogen between the two sites induced by such factors as a change in temperature, application of an electric field, and irradiation with light both tautomers may be present at symmetry-independent sites in the crystal different tautomers may be present in different crystal modifications and the presence of molecular substituents that do not directly affect the properties of the hydrogen bond may influence the tautomerism via the crystal structure. 

Malonaldehyde, CH2(CHO)2, exists as an intramolecularly hydrogen-bonded enol (86) in the vapour phase. Molecular dynamics calculations suggest that while a short 0—0 distance favours proton transfer to an (identical) tautomer, such proximity is neither a sufficient nor a necessary condition. 

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