Stability, tautomers

Hydrogen bonding plays a major role in pyrazolone tautomerism, and the formation of a chelate structure can shift the equilibrium towards the chelated form. Structures (135) and (136) are two representative examples of such stabilized tautomers. Structure (137) is a hypothetical example of stabilization of the NH tautomer. 

Since polar solvents would be expected to stabilize polar forms, a retreat towards the hydroxy tautomer (71) would be predicted in solvents less polar than water, and in the vapour phase. This is borne out in practice at equilibrium both 2- and 4-hydroxypyridine (as well as the 3-hydroxy compound, which even in water exists as an approximate 1 1 mixture of OH and NH forms) exist as such, rather than as the pyridinones. However, the 2- and 4-quinolinones remain in the NH (keto) forms, even in the vapour phase. Hydrocarbon or other solvents of very low polarity would be expected to give results similar to those in the vapour phase, but intermolecular association by hydrogen bonding often leads to a considerably greater proportion of polar tautomers being present than would otherwise have been predicted (77ACR186, 78JOC177). 

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. 

Potential C-hydroxy compounds usually exist as the 0x0 tautomers, unless the hydroxy tautomer is appreciably stabilized by electron withdrawing or chelating substituents. The... 

Mercapto derivatives of furan, thiophene, selenophene (77ACS(B)198) and pyrrole (72AJC985) all exist predominantly in the thiol form. 2-Mercaptobenzothiophene is also a thiol (70JCS(C)243i) whereas 2-mercaptoindole is mainly indoline-2-thione (89) (69CPB550). The finely balanced nature of this system is indicated by the fact that a 3-aryl, but not a 3-alkyl, substituent will stabilize the 2-thiol form, whereas for 3-aryl-fV-methyl derivatives the 2-thione tautomer is preferred (71CC836). 

Schmidt reaction of ketones, 7, 530 from thienylnitrenes, 4, 820 tautomers, 7, 492 thermal reactions, 7, 503 transition metal complexes reactivity, 7, 28 tungsten complexes, 7, 523 UV spectra, 7, 501 X-ray analysis, 7, 494 1 H-Azepines conformation, 7, 492 cycloaddition reactions, 7, 520, 522 dimerization, 7, 508 H NMR, 7, 495 isomerization, 7, 519 metal complexes, 7, 512 photoaddition reactions with oxygen, 7, 523 protonation, 7, 509 ring contractions, 7, 506 sigmatropic rearrangements, 7, 506 stability, 7, 492 N-substituted mass spectra, 7, 501 rearrangements, 7, 504 synthesis, 7, 536-537... 

Carbanions derived from carbonyl compoimds are often referred to as etiolates. This name is derived from the enol tautomer of carbonyl compounds. The resonance-stabilized enolate anion is the conjugate base of both the keto and enol forms of carbonyl... 

Although nitrosation of (l-dicarbonyl compounds becomes increasingly more facile upon successive replacement of the a alkyl groups with perfluoroalkyl groups because of the increased ionization of the perfluorinated enolate (equation 7), the stability of the nitrosodiketone tautomers decreases Thus, 1,1,1-trifluoro pentane-2,4-dione and 1,1,1,5,5,5-hexafluoropentane 2,4 dione mtrosate much faster than penta-2,4 dione but yield ketoximes, which decompose upon workup... 

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 )... 

A large number of Brpnsted and Lewis acid catalysts have been employed in the Fischer indole synthesis. Only a few have been found to be sufficiently useful for general use. It is worth noting that some Fischer indolizations are unsuccessful simply due to the sensitivity of the reaction intermediates or products under acidic conditions. In many such cases the thermal indolization process may be of use if the reaction intermediates or products are thermally stable (vide infra). If the products (intermediates) are labile to either thermal or acidic conditions, the use of pyridine chloride in pyridine or biphasic conditions are employed. The general mechanism for the acid catalyzed reaction is believed to be facilitated by the equilibrium between the aryl-hydrazone 13 (R = FF or Lewis acid) and the ene-hydrazine tautomer 14, presumably stabilizing the latter intermediate 14 by either protonation or complex formation (i.e. Lewis acid) at the more basic nitrogen atom (i.e. the 2-nitrogen atom in the arylhydrazone) is important. 

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-... 

Generally the name of a compound should correspond to the most stable tautomer (76AHCS1, p. 5). This is often problematic when several tautomers have similar stabilities, but is a simple and reasonable rule whose violation could lead to naming phenol as cyclohexadienone. Different types of tautomerism use different types of nomenclature. For instance, in the case of annular tautomers both are named, e.g., 4(5)-methylimidazole, while for functional tautomerism, usually the name of an individual tautomer is used because to name all would be cumbersome. In the case of crystal structures, the name should reflect the tautomer actually found therefore, 3-nitropyrazole should be named as such (97JPOC637) and not as 3(5)-nitropyrazole. 

The predominance in the gas phase of the CH tautomers in the case of several pyrazolinones including one 3-aminopyrazolin-5-one was demonstrated by PES [88JCS(P2)641] this result is consistent with previous findings (76AHCS1, p. 325). The same technique was applied to the study of the amino/imino equilibrium in 9-amino and 9-(methylamino)acridines [91MI(61)166] although both tautomers have similar stabilities, the experimental data are in better agreement with the amino tautomer. 

This technique provides quantitative information about tautomeric equilibria in the gas phase. The results are often complementary to those obtained by mass spectrometry (Section VII,E). In principle, gas-phase proton affinities, as determined by ICR, should provide quantitative data on tautomeric equilibria. The problem is the need to correct the measured values for the model compounds, generally methyl derivatives, by the so-called N-, 0-, or S-methylation effect. Since the difference in stability between tautomers is generally not too large (otherwise determination of the most stable tautomer is trivial) and since the methylation effects are difficult to calculate, the result is that proton affinity measurements allow only semi-quantitative estimates of individual tautomer stabilities. This is a problem similar to but more severe than that encountered in the method using solution basicities (76AHCS1, p. 20). 

Electron-releasing substituents stabilize the isoindolenine tautomer 7, whereas eleetron-withdrawing groups have the opposite effect. In Table IV some data are given. 

Since Woodward s work on the synthesis of chlorophyll a (60JA3800) it is known that the intrinsic unstable thioformyl moiety can be stabilized by the delocalization effect of heterocyclic systems. Recently the synthesis of 2-amino- and 3-aminothioformylthiophenes (and furans) and the corresponding benzo derivatives (Scheme 19) has been reported (96S1185). These compounds exist as amino tautomers (91S609 96S1185). 

Additional sections of this chapter cover (1) tautomeric reactions of azoles and their derivatives in electronically excited states and (2) stabilization of certain tautomers in their metal complexes. 

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