Tautomers, defined

Interpolation methods based on N chemical shifts require the use of the general equations.Those reported in the previous edition (76AHCSl,p. 29, see also 82JOC5132) have been slightly modified for the present purpose. We call / x the observed average property, and the property of the individual tautomers (A or B), / ma and / mb a corresponding property that can be measured (in a model compound or in the solid state) or calculated theoretically, and P and / b the correction factors defined as P = -... 

The imbalance between and NMR studies in the solid state (Section VI,F) partly reflects the fact that it is easier to introduce N than into heterocyclic compounds, particularly azoles (DNMR in the solid state usually requires isotopic enrichment). Compared to solution studies, solid-state intermolecular proton transfer between tautomers has the enormous advantage that the structure of the species involved is precisely defined. 

JCS(P2)57]. It follows, therefore, that the destabilizing lone-pair repulsion effeet appeared in the H tautomer 25a overeomes positive eontribu-tion of its greater aromatie stabilization relative to 25b and serves as a major faetor defining the relative stability of the tautomers. 

The conclusions about the influence of azole ring substituents on the tautomeric equilibria are summarized in Table VIII. Although sufficient data are available for pyrazoles and imidazoles, it is difficult to correlate them within any well-defined scheme. The energy differences between pairs of tautomers are generally quite small and attempts to analyze these using, for example, the Taft-Topson model failed [95JCR(S)172]. In the case of mono-substituted compounds, Hammet-type equations... 

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. 

It should finally be noted that the amount of the neutral and zweitterionic forms of a compound in solution is determined by its tatuomeric equilibrium constant, defined as Kz = cz/cn. Therefore, the neutral species and the zwitterion coexist around the isoelectric pH, and membrane permeation is conditioned by Kx and by the partition coefficient values of both tautomers. 

They also defined a state of metaionie in which no structural formula for the so-called tautomers corresponds to the "real" structure of the reacting molecule. The Kekule forms of benzene are examples of metaionie. 74... 

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. 

Nazarov-like cyclization to give the carbozole tautomer 67. The latter undergoes a hydrogen shift and deprotonation to give the observed product. Typically, the isolated yields of carbazole are low because it reacts with nitrenium ion at the diffusion limited rate giving a poorly defined set of oxidized oligomeric products. Maximal yields of carbazole are obtained only when the reaction is carried out under highly dilute conditions. 

The equilibrium constant for a tautomeric interconversion is simply the ratio of the mole fractions of the two forms for example, the ratio of enol to oxo forms of acetone12 in water at 25°C is 6.0 x 10 9, while that for isobutyraldehyde is 1.3 x ICE4. The ratio of 2-hydroxypyridine to 2-pyridone is about 10 3 in water but increases to 0.6 in a hydrocarbon solvent and to 2.5 in the vapor phase.13 14 The ratio of dipolar ion to uncharged pyridoxine (Eq. 2-5) is 4 at 25°C in water.15 The ratios of tautomers B, C, and D to the tautomer A of uracil (Eq. 2-4) are small, but it is difficult to measure them quantitatively.16 These tautomeric ratios are defined for given overall states of protonation (see Eq. 6-82). The constants are independent of pH but will change if the overall state of protonation of the molecule is changed. They may also be altered by... 

The electrophilic functionalization of carbonyl and carboxyl compounds next to the C=0 double bond generally proceeds in a single step via an SE reaction of the enol tautomer. The identification of suitable substrates for this type of reaction requires rough knowledge of the extent to which the respective enolization occurs. The enolization equilibrium constants KE or their —more easy-to-handle—negative logarithm values, the so-called pXE values, provide a quantitative measure thereof. These measures are defined as follows ... 

For the partially deuterated benzoic acid (C6D5COOH), the solid state H NMR spectrum is dominated by the intra-dimer H- H dipole-dipole interaction. In a single crystal, both tautomers A and B are characterised by a well-defined interproton vector with respect to the direction of the magnetic field (Fig. 1). Proton motion modulates the H- H dipole-dipole interactions, which in turn affects the H NMR lineshape and the spin-lattice relaxation time. It has been shown that spin-lattice relaxation times are sensitive to the proton dynamics over the temperature range from 10 K to 300 K, and at low temperatures incoherent quantum tunnelling characterises the proton dynamics. A dipolar splitting of about 16 kHz is observed at 20 K. From the orientation dependence of the dipolar splitting, the... 

It is long known that -diketones, which exist as keto-enol tautomers, have a well defined electron transfer ability. In general, they exibit a first, partially chemically reversible, one-electron rednction to the corresponding enolato monoanion (minor amounts of the corresponding dimer are also formed), which in tnrn undergoes either a reduction process or an irreversible oxidation. The electrode potentials of a selection of symmetrically substituted (R = R ) S-diketones are reported in Table 7. 

The concept of valence tautomerism was introduced to define the properties of a molecular adduct A — D+ (A = acceptor, D = donor) whose electronic ground state is described by two or more isomers with different charge distributions. The interconversion between different valence tautomers is accomplished by an intramolecular electron transfer according to the following equation A-(D+) (A+)-D. To... 

Quantum-mechanical studies on the tautomerism of heterocyclic compounds involve, in general, two aspects. The first deals with the prediction of physicochemical properties of defined tautomeric forms (e.g., ultraviolet spectra, dipole moments, ionization potentials, etc.). This seems to be easy to handle. Using any semiempirical or nonempirical quantum-mechanical computational method, depending on approximations involved in the method, we are able to calculate properties that, more or less, agree with experimental values. Calculations of this type do not contribute to a direct estimation of the relative stability of the tautomers, however they are particularly important for cases in which a tautomeric form of a compound is so rare that it is not possible to measure it directly. 

The second covers the prediction of the relative stability of tautomers in vapor phase and the estimation of the tautomeric constant in this phase, prediction of the influence of substituents (e.g., methyl group, halogen atom) on the shift of tautomeric equilibrium (the relative change of tautomeric constant caused by substituents), and even the estimation of the stability of defined tautomers in solution. Obtaining these properties is much more complicated. The difficulties connected with an attempt to apply quantum chemistry in this case will be discussed in the next section. 

Here the difference in solvation energy of two tautomers in their excited state is defined as Af a,b( ) = Af A>B + hc( Ava - A B), where Ai> = f(v) -Hs) indicates the shift of the 0-0 (or maximum) absorption band positions of the tautomers on going from vapor phase to solution. 

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