Tautomerism resonance

Each of the tautomeric forms of a substance may show electronic resonance tautomerism and resonance are not mutually exclusive. Let us discuss 5-methylpyrazole as an example. This substance exists in two tautomeric forms, A and B, differing in the position of the N-hydrogen atom. 

Dissolve ca. 0 2 g. of product (I) in cold ethanol, and add with shaking 1-2 drops of dilute sulphuric acid. A deep purple coloration appears at once. This shows that salt formation has occurred on the quinoline nitrogen atom to form the cation (Ha), which will form a resonance hybrid with the quinonoid form tils). [Note that the forms (IIa) and (11b) differ only in electron position, and they are not therefore tautomeric.] If, hoAvever, salt formation had occurred on the dimethylaniino group to give the cation (III), thrs charge separiition could not occur, and the deep colour would be absent. 

Clearly, in the case of (66) two amide tautomers (72) and (73) are possible, but if both hydroxyl protons tautomerize to the nitrogen atoms one amide bond then becomes formally cross-conjugated and its normal resonance stabilization is not developed (c/. 74). Indeed, part of the driving force for the reactions may come from this feature, since once the cycloaddition (of 72 or 73) has occurred the double bond shift results in an intermediate imidic acid which should rapidly tautomerize. In addition, literature precedent suggests that betaines such as (74) may also be present and clearly this opens avenues for alternative mechanistic pathways. 

The tautomeric equilibria of these heterocycles always involve one or more non-aromatic tautomers. An important factor in determining the extent to which such non-aromatic tautomers are involved is the magnitude of the potential loss of resonance energy. 

Exocyclic conjugation causes a small upheld shift of the ring hydrogen resonances, as can be seen in Table 6. The increase in tr-bond hxation also results in an increase in the 4,5 coupling constant to about 6.0 Hz. The use of coupling constants for the investigation of tautomerism is discussed in Section 4.17.5. 

Some results have been published on 2-alkylisothiazole-3- and -5-thiones (75CJC836, 80JCS(P 1)2693). As expected, the resonance of the carbon attached to the exocyclic sulfur atom is shifted downfield, to around 185 p.p.m. in the case of the 3-thiones and to over 190p.p.m. for the 5-thione. It is possible that CNMR chemical shifts could be used to investigate tautomerism in related compounds. Saccharin has carbon resonances at 161.0 (3), 127.9 (3a), 125.1 (4), 134.7 and 135.5 (5 and-6), 121.2 (7) and 139.5 (7a) p.p.m. in DMSO solution <82UP41700>. 

The salts of some enamines crystallize as hydrates. In such cases it is possible that they are derived from either the tautomeric carbinolamine or the amino ketone forms. Amino ketone salts (93) ( = 5, 11) can serve as examples. The proton resonance spectra of 93 show that these salts exist in the open-chain forms in trifluoroacetic acid solution, rather than in the ring-closed forms (94, n = 5, 11). The spectrum of the 6-methylamino-l-phenylhexanone cation shows a multiplet at about 2.15 ppm for phenyl, a triplet for the N-methyl centered at 7.0 ppm and overlapped by signals for the methylene protons at about 8.2 ppm. The spectrum of 93 ( = 11) was similar. These assignments were confirmed by determination of the spectrum in deuterium oxide. Here the N-methyl group of 93 showed a sharp singlet at about 7.4 ppm since the splitting in —NDjMe was much reduced from that of the undeuterated compound. 

Up to the present the principal interest in heteroaromatic tautomeric systems has been the determination of the position of equilibrium, although methods for studying fast proton-transfer reactions (e.g., fluorescence spectroscopy and proton resonance ) are now becoming available, and more interest is being shown in reactions of this type (see, e.g., references 21 and 22 and the references therein). Thus, the reactions of the imidazolium cation and imidazole with hydroxyl and hydrogen ions, respectively, have recently been demonstrated to be diffusion controlled. ... 

In general, physical methods have been used to study tautomerism more successfully than chemical methods, and, of the physical methods, those involving measurements of basicities and ultraviolet spectra are the most important, followed by those involving measurement of infrared and proton resonance spectra. An attempt is made here to delineate the scope and to indicate the advantages and disadvantages of the various methods. A short review by Mason of the application of spectroscopic methods appeared in 1955. Recently a set of reviews on the applications of physical methods to heterocyclic chemistry has appeared, which treats incidentally the determination of tautomeric structure. 

The pKa values of 4-hydroxypyridine 1-oxide (51 52) and the methylated derivatives of both tautomeric forms indicate that the parent compound exists as a mixture containing comparable amounts of both forms in aqueous solution. Nuclear magnetic resonance spectra support this conclusion, but the ultraviolet spectra of the tautomeric compound and both alkylated derivatives are too similar to give information concerning the structural nature of the former. ... 

In 1955 Boyer d al challenged this formulation, and suggested a static, mesomeric system rather than a dynamic, tautomeric one, with Contributing structures of type 9 and 10 to a symmetrical resonance hybrid, proposing the name -o-dinitrosobenzene for the parent System. This notion, however, raised more problems than it solved,... 

The first evidence for an unsymmetrical structure for the benzo-furoxan molecule and for the tautomerism of Eq. (3) was provided in 1961 by several groups of workers," using proton resonance... 

The 1-oxide 3-oxide tautomerism [Eq. (3), p. 4] has been discussed earlier (Sections II and III,C) in connection with the problem of the structure of benzofuroxan. A second type of rearrangement involves the furoxan ring and an adjacent substituent group, and arose out of a suggestion of Bailey and Case that 4-nitro-benzofuroxan might be a resonance hybrid of type (57)-(-> (58), rather than 57. NMR ruled out this possibility the three protons present in... 

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-... 

Nuclear magnetic resonance spectra of all four parent compounds have been measured and analyzed.The powerful potentialities of NMR as a tool in the study of covalent hydration, tautomerism, or protonation have, however, as yet received no consideration for the pyridopyrimidines. NMR spectra have been used to distinguish between pyrido[3,2-d]pyrimidines. and isomeric N-bridgehead compounds such as pyrimido[l,2- ]pyrimidines and in several other structural assignments (cf. 74 and 75). 

Lieber et have come to the same conclusion by an investigation of the ultraviolet spectra and dipole moments of 5-amino-, 5-methyl-amino-, and 5-dimethylamino-l, 2,3,4-thiatriazole. The dimethylamino derivative, in which no tautomerism is possible, shows the same characteristic absorption near 250 m/A as the unsubstituted compound and the monomethyl derivative. The dipole moments of the three compounds differ very little. These moments are quite large (5.8 Debye), showing that ionic resonance forms of type 9 contribute considerably to the structure of these compounds. 

Generation of reaction networks with RAIN resonance structures and tautomerism Solid-state NMR studies of reversible 1,5-H shifts Tautomeric equilibria (AMI, MNDO, PM3)... 

Resonance energies and tautomerism of substituted aromatic heterocycles and their benzo derivatives Reaction-field-supermolecule approach to calculation of solvent effects... 

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