Tautomers tautomerization scheme

Dimerization of pyridinium-3-olates (86) is also induced photochemically. In accord with theory the structure of the photodimers differs from that of the thermal dimers. A-Phenylpyridinium-3-olate (101) upon irradiation gives dimer 103 together with the bicyclic valence tautomer 102 (Scheme 4). This valence tautomerism (101 - 102) is analogous to that of pyrylium-3-... 

The aromatic imidazole N-oxides have structure 245. The parent compound 246 displays tautomerism between the N-oxide tautomer 246 and the 1-hydroximidazole tautomer 247 (Scheme 68). 1-Hydroxyimidazole 247 and substituted 1 -hyd roxyimidazoIes 249 belong to a separate group of compounds, which is not discussed in the present review. 

Comparison of the UV spectra of 5-amino-2-(2-furyl)-l,2,4-triazolo[l,5-c]quinazolines (196) and its 5-methylamino derivative (197) in neutral, acidic, and basic media with the spectra of the two tautomerically locked derivatives—2- (2-fury 1) -5-dimethylamino-1,2,4-triazolo [ 1,5-c]quinazolines (198) (amino-locked tautomers) and the imino-locked tautomers 2-(2-furyl)-5-imino-6-methyl-1,2,4-triazolo[ 1,5-c]quinazolines (199)—indicated that compounds 196 and 197 are best represented as a mixture of their amino and imino tautomers (88JMC1014) (Scheme 75). 

Aminoimidazoles are rather unstable and have not been studied extensively, but despite the absence of a specific study of their tautomerism it is possible to gather some evidence in favour of the amino tautomer of types (35 X = NH) (39 X = NH) or (47 X = NH). Imino structures (e.g. 34, 38, 44 X = NH) require the appropriate CH signals in the NMR spectrum these are absent, and the IR spectra display characteristic bands for NH2. The X-ray structure for 4-acetamido-2-bromo-5-isopropyl-1-methylimidazole confirms the structure (65) rather than the tautomer (66) (Scheme 21). On the basis of CNMR evidence, 2-arylamino-2-imidazolines prefer to exist in the arylimino forms (B-77MI40600). 

Our recent studies on phenol oxidation by oxoiron(IV) and oxomanganese(IV) porphyrins in aqueous solution (pH 7.6) have shown that the initial step in these reactions is H atom abstraction to generate a phenoxyl radical (Scheme 3). e kinetic isotope effect measured in the present study indicates that H atom abstraction also occurs in the rate determining step of the oxidation of azonaphthol dyes by 1. However, although the structures of azonaphthol dyes are normally shown as azo compounds, in aqueous solution they are in a rapid dynamic equilibrium with their hydrazone tautomers the latter isomer being the dominant species (Scheme 4). This complicates kinetic studies on the dyes, since the substrate is in effect a mixture of two compounds. Consequently one or both the tautomers may be the active form of the substrate providing the H atom for the oxidant. It is important to note that, irrespective of which tautomer is the reactive substrate, H atom abstraction leads to a common azonaphthoxyl radical intermediate and subsequent reactions of this species should be independent of the initial tautomerism (Scheme 5). 

This chapter describes the chemistry of carbanionic species having a carbonyl function at the -posi-tion, relative newcomers among synthetically useful carbanionic species. The chemistry of homoenolates is complicated by the problem of tautomerism between oxyanionic and carbanionic isomers through a process that formally involves homoconjugation. The synthetic problem caused by this tautomerism is much more severe in homoenolate chemistry (Scheme 1) than in enolate chemistry (Scheme 2), which also has a similar problem, since the carbanionic tautomer (1 Scheme 1) once formed often undergoes rapid and irreversible cyclization to the oxyanionic tautomer (2), and rarely acts as a carbon nucleophile. Until recently, therefore, chemists have not been able to make use of carbanionic homoenolates for organic syntheses. " However, a large number of useful homoenolate reactions have recently been discovered, and are described in this chapter. 

The ring-ring tautomerism (Scheme 5.6) of 5-hydrazino-A -isoxazohne (8a) 5-hydroxyamino-A -pyrazohne type (8b) was studied both in solution and in the sohd state [20]. The presence and equihbria of the ring-ring tautomers were exemphfied by the chemical shifts of 3-Me (8a 12.7-13.2 ppm, 8b 15.6-16.7 ppm) and C-5 (8a 88.3-99.8ppm, 8b 83.4-83.6ppm), respectively. Other 5( C) values as well as H NMR spectra proved to be quite similar. 

An interesting type of keto-enol tautomerism, called cyclic anhydride-end tautomerism (Scheme 5.14), was published [45]. NMR spectroscopy was employed to estimate the equilibrium the ratio of the anhydride tautomer 20a and the enol form 20b was 7 1 [45]. 

Finally, the Se NMR evidence of l-mesityl-l,3-dihydro-imidazole-2-selone was much more consistent with the selone 43a (5( Se) = 28ppm, Vsec = 231 Hz] than with the selenol tautomer 43b (Scheme 5.34) [83]. The free energy of activation of prototropic tautomerism of ethyl 2H-perimidine-2-carboxylate 44 (Scheme 5.35)... 

The azo-hydrazone tautomerism (Scheme 5.51) is fast on the NMR timescale. Both i5( N) and Vn-h tautomers are characteristically different and can... 

The tautomeric 2-hydroxypyrroles undergo base-catalyzed reactions probably through deprotonation to the ambident conjugate base (Scheme 71). 2-Hydroxyfurans (e.g. 178) similarly exist in ketonic forms (179) and (180), the most favoured tautomer being the conjugated 2(5//)-furanone (180)... 

Complex tautomerism for azoles with heteroatoms in the 1,2-positions occurs for pyrazoles which are not substituted on nitrogen. Scheme 10 shows the four important tautomeric structures (148)-(151) for 3-methylpyrazolin-5-one, and (152) and (153) as examples of other possible structures. A detailed investigation of this system disclosed that in aqueous solution (polar medium) the importance of the tautomers is (149) > (151) (150) or (148), whereas in cyclohexane solution (non-polar medium) (151) > (148) (149) or (150). 

In a neutral azole, the apparent rate of formation of an A-substituted derivative depends on the rate of reaction of a given tautomer and on the tautomeric equilibrium constant. For example, with a 3(5)-substituted pyrazole such as (199), which exists as a mixture of two tautomers (199a) and (199b) in equilibrium, the product composition [(200)]/[(201)] is a function of the rate constants Ha and fcs, as well as of the composition of the tautomeric mixture (Scheme 16) <76AHC(Si)l). 

Interconversion between two tautomeric structures can occur via discrete cationic or anionic intermediates (scheme 24, where T is an anion capable of reacting with a proton at a minimum of two distinct sites). Alternatively, interconversion can occur by simultaneous loss and gain of different protons (scheme 25, w here T has the same definition as in scheme 24). These mechanisms are well established for acyclic compounds, but they have been much less thoroughly investigated for heteroaromatic systems. The rate of interconversion of two tautomers is greatest when both of the alternative atoms to which the mobile proton can be attached arc hetero atoms, and isolation of the separate isomers is usually impossible in this case. If one of the alternative atoms involved in the tautomerization is carbon, the rate of interconversion is somewhat slower, but still fast. When both of the atoms in question are carbon, however, interconversion is... 

The determination of pi a values is probably the most generally useful method for the investigation of tautomerism. This method was first employed in the heterocyclic field in the early 1950 s by Tucker and Irvin and by Angyal and Angyal. There are two empirical dissociation constants, and K2, for the conjugate acid (HXH+) of a tautomeric compound. Constants Kt and K2 are, in effect, a summation of the true dissociation constants Ka, Kb, Kc, and Kd of the individual tautomeric forms (see scheme 43, where XH and HX are tautomers) and the tautomeric constant, Kt] these constants are related by the following equations ... 

A situation found in very few cases in crystals, but very important for the understanding of the mechanism of tautomeric change, is when two different tautomers are present in the same unit cell (Section V,D,2) and they are rapidly equilibrating. This is the case for 5-methyl-4,5,6,7-tetrahydroinda-zole (4) where tautomers 4a and 4b exist in a 53/47 ratio (Scheme 2) (97CEJ121). 

Annular tautomerism of azoles and benzazoles [the nonaromatic tautomers of imidazole 17, 2H and 4(5)H have been calculated at the MP2/6-31G level to be about 15 kcal mol less stable than the IH tautomer (95JOC2865)]. We present here the case of 4(5)-substituted imidazoles, different from the histamine, histidine, and derivatives already discussed. By analogy with these histamines, 4-methylimidazole 17a is often named distal [N(t)H] and 5-methylimidazole 17b, proximal [N(7t)H] (Scheme 9). 

Pyrazolinones and other five-membered compounds (functional tautomerism). These studies have often used the most simple but rather experimentally neglected pyrazolin-5-one 19. Its four tautomers are called CH 19a, NH 19b, 5-OH 19c, and 3-OH 19c (Scheme 10) [76AHCS1, p. 313]. 

The study of tautomerism using H NMR spectroscopy is simple when the tautomers give separate signals (84B2906) otherwise, interpolation methods need to be applied, which entail several sources of imprecision [83JPR(325)238]. A paper reports the observation of two NH signals for the N-labeled tautomers of 3(5)-methyl-5(3)-phenylpyrazole (45) in toluene-dg at 190 K (Scheme 15) [92JCS(P2)1737]. 

There was never any doubt that the major tautomer in the case of in-dazole 27 is the IH-one 27a (Scheme 16), and C chemical shifts compared with those of the two V-methyl derivatives confirmed that this is the case in DMSO-dg (770MR716). NMR has been used to determine the equilibrium isomeric composition of N-CHROH, N-C(CH3)20H, N-COCH3 and N-Si(CH3)3 derivatives for azoles and benzazoles, the conclu-sipn being that this composition parallels the annular tautomeric composition [78JCS(P2)99]. The tautomerism of 1-hydroxybenzotriazole was also studied... 

Uracil, thymine, and cytosine have been studied using this technique (89JA2308 and references therein). For uracil and thymine, the dioxo tautomer predominates in the case of cytosine (70), three tautomers were detected, 70a, 70b, and 70c, the last one being the least abundant. The gas-phase tautomeric equilibrium of 2-pyridone 15a and 2-hydroxypyridine 15b has been studied by MW spectroscopy (93JPC46) using both a conventional spectrometer and a jet-cooled millimeter-wave spectrometer. The relative abundances are 3 1 in favor of the hydroxy form 15b, which exists in the Z conformation shown (Scheme 23). 

A tautomeric equilibrium between quinone and quinone methide tautomers has been proposed to exist for the compounds which are obtained by oxidation of 5,6-dihydroxy indole (Scheme 18) (92TL3045). 

Apart from the IH and 2H tautomers 2a and 2b, isomeric forms in which the migrating proton takes up its position on one of the carbon atoms in the ring are formally possible. For the case of unsubstituted pyrazole 2, R = r2 = r3 = tjjg tautomeric equilibrium should be represented by the scheme involving 4H 2e and a pair of degenerate 5H species 2c and 2d (Scheme 2). 

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