Contents 5 TAUTOMERISM

The differential effects of sterlc hindrance and tautomeric content in the imidazole series are illustrated in Scheme 6 (80AHC(27)24i). 

The tautomeric equilibria of 5-hydroxy-3-aminopyrazoles 226 are affected by the substituent R" (Scheme 77) [76AHC(S1), p. 467]. While structure 226b is usually the major form, for some compounds of type 226 (R = COMe, COPh) the equilibrium content of 226c may reach 60% (74BSF291). 

Ring-chain tautomerism of derivatives of 1,3,4-triazolidines 283 involves the equilibrium of three isomeric forms (Scheme 102) [90TL3927 96AHC(66)1, p. 33], In DMSO solution, the predominant form (about 70%)is 283c, the content of 283a and 283b varied between 13-25% and 5-17% respectively. 

At its best, the study of solvent kies by the formalism given can be used to learn about proton content and activation in the transition state. For this reason it is known as the proton inventory technique. The kinetics of decay of the lowest-energy electronic excited state of 7-azaindole illustrates the technique.25 Laser flash photolysis techniques (Section 11.6) were used to evaluate the rate constant for this very fast reaction. From the results it was suggested that, in alcohol, a double-proton tautomerism was mediated by a single molecule of solvent such that only two protons are involved in the transition state. In water, on the other hand, the excited state tautomerism is frustrated such that two water molecules may play separate roles. Diagrams for possible transition states that can be suggested from the data are shown, where of course any of the H s might be D s. 

Tautomerism both in the solid state and in solution is confirmed by infrared spectroscopic measurements on all three compounds [54,55]. The highest content of ketohydrazone form within the three isomeric phenylazonaphthols occurs, in solution, with 2-phenylazo-l-naphthol [56]. A 15N-n.m.r. study of some azo dyes derived from H acid and related intermediates has confirmed the dominance of the ketohydrazone tautomer [57]. Similar findings have been obtained using high-field H- and 13C-n.m.r. spectroscopy [58]. 

K. H. Meyer s bromine method 1 makes it possible to determine the enol content in almost all solutions of tautomeric substances. 

Further evidenee for the intermediacy of the imidoyl halide 24 can be taken from the formation of the aminodicyanostyrene 22, formed as a minor product in the amination of 20 (Scheme 11.19) (73RTC471). As already mentioned, 22 eontains the same content as the starting material, and based on this experimental result its formation from the imidoyl halide seems now straightforward. In this strong basic solution the tautomeric con-... 

The number of molecules which react in unit time is far smaller than the number entering into collision this shows that those which suffer transformation are in some way in an exceptional state. The attainment of this exceptional state is very much favoured by increase of temperature molecules of high energy content are thus indicated, since the assumption of specific tautomeric changes into an active form is impossible in the case of quite simple molecules. The law of variation with temperature of the number of molecules the energy of which exceeds an assigned value is, moreover, precisely the same as that of the change in reaction velocity. 

Wierzchowski et al.325 recorded in aqueous medium the IR specta of the monoanions of thymine and of 1-methyl- and 3-methylthymine. The data demonstrated that the monoanions of thymine consist of an equilibrium mixture of two tautomeric forms 34 and 35 corresponding to the dissociation of the N-l or the N-3 protons, respectively. The fractional content of the thymine monoanion 35 in the mixture of the two monoanions was evaluated from the extinction of the characteristic bands of the anion of thymine and 1-methylthymine to be 0.4. A marked shift in equilibrium of the tautomers was observed on going from a NaCO in D20 solution of thymine to NaOD in 75% dioxan-D20. Calculation of the tautomeric equilibrium showed that in 75% dioxan the fraction of 35 was 0.25, compared to 0.4 in aqueous medium. 

The effect of added water was also calculated for the five tautomeric forms. The results showed that the spectrum corresponded principally to the dithiol 8 (Figure 1) and monothiols 5-7, which overlap the best of the features enhanced on the spectrum measured at high water content solution. These results suggest that a specific solute-solvent interaction is present favoring the dithiols and monothiols isomers indicating that the hydrogen bond in solute-water is a 1 n complex. 

The solvent, temperature, and substituent (R and R1) -dependent ring-chain tautomerism of 2-pyridylaminomethylenemalononitriles (167 168) was studied (86JOC2988). 2-Pyridylaminomethylenemalo-nonitriles were prepared in the reaction of 2-aminopyridines and 2-(l-ethoxyalkylidene)malononitrile in ethanol at room temperature or in a melt at 120°C, and in a one-pot reaction, starting from 2-aminopyridines, a triethyl orthoester, and malononitrile at 110°C for 10 minutes. The content of the equilibrium mixture of 2-pyridylaminomethylenemalononitrile 167 (R = R1 = H) is shown in Table X. Elevation of the temperature increased the proportion of the chain tautomer. The ratio between the two tautomeric forms 167 and 168 is influenced primarily by the steric properties of substituents R and R1 in positions 6(6) and 3(9), respectively,... 

Solvent and concentration effects on keto-enol tautomerization have been investigated in DMSO-water mixtures and aqueous micellar solutions, for 2-acetylcyclo-hexanone and 2-acetyl-1-tetralone.286 Dramatic rate increases aboves 60% DMSO content have been explained in terms of solvent structure solvent polarity alone cannot rationalize the effect. 

In complete agreement with the deductions from infrared data, the calculations estimate the tautomers 37, 40, and 43 as the most stable forms of 2-hydroxypurine, 6-hydroxypurine, and 8-hydroxypurine, respectively, followed very closely, however, by tautomers 34 and 39 for the first two isomers. Their existence as mixtures of tautomeric forms in comparable proportions seems therefore highly probable. On a relative scale the most stable of the three isomers should be the 8-hydroxy one (certainly because of the high content of its 77-electronic delocalization), which should, in fact, be appreciably more stable than the 2- or 6-isomers, which are predicted to be of comparable stability. 

Keto-Enol Tautomerism End Content of Carbonyl and Carboxyl Compounds... 

The bottom line complements Figure 12.1 by adding the >Ky values of representative ketones. The comparison of E G reveals the same substituent effects that are familiar from the analogous aldehydes A-C the enol content is increased by alkyl substituents in the on-position, and even more so by aryl substituents in the a-position. The ketone H in Figure 12.1, the nonexistent isophenol has by far the highest propensity to enolization of all the carbonyl compounds shown. The reason, of course, is that the tautomeric enol, phenol, is favored because of its aromaticity and thus particularly efficient C=C double bond stabilization. 

The order in which the various topics are discussed is evident from the table of contents. It should be pointed out that thiones are treated together with oxazolones, while aminooxazoles, which are tautomeric with oxazoleimines, will usually be found in sections dealing with oxazoles. 

Another example is the y9-ketonitrile (6a,b). Because of the linearity of the cyano group, a cyclic structure with an intramolecular hydrogen bond is impossible. As predicted, it is found that the enol content is greater in polar than in apolar solvents [53], In general, for the protomer pairs in which the enol cannot form an intramolecular hydrogen bond, such as (5a) (5c),ihc tautomeric equiUbrium seems to be controlled almost completely by the hydrogen-bond acceptor property (Lewis basicity) of the solvent. EPD solvents enhance the enol content strongly cf. (5a) in Table 4-2. 

In the case of the tautomerization between 9-anthrone, (9a), and 9-anthranol, (9b), the equilibrium lies practically completely on the side of the keto form (9a) in the gas phase as well as in inert solvents such as wo-octane and benzene e.g. in benzene at 20 °C, the enol content is 0.25 cmol/mol [60, 134]. 

The ketimine (13a), prepared from desoxybenzoin and aniline, is also subject to a solvent-dependent tautomerism called imine/enamine tautomerism. The enamine content of a solution of (13a) increases in the order tetrachloromethane (31 cmol/mol at 35 °C), [Dsjpyridine (47.5 cmol/mol at 55 °C), and [Dejdimethyl sulfoxide (67 cmol/mol at 55 °C) [69], Hydrogen-bond acceptor solvents favour the enamine form (13b) due to hydrogen-bonding, whereas in less polar and apolar solvents the equilibrium is shifted towards the imine form / 13a) [69]. 

Compounds capable of a solvent-dependent amino/imino tautomerism are 3-methylcytosine (14a,b) and 1-alkyladenines [69b]. It has been shown by IR and UV/Vis spectroscopy that, in all cases, the imino forms such as (14b) predominate in nonpolar media e.g. 1,4-dioxane). However, the content of the amino form (14a) increases with increasing solvent polarity, and in aqueous solution the amino form predominates [69b]. Further interesting examples of solvent-dependent tautomeric amino/imino equilibria... 

Table 12. Oxidation potentials, Ep, of pora-substituted 2-aryl-propionaldehydes 88 and their tautomeric enols 89 in acetonitrile/DMSO [171] compared with calculated , 2 (89)- The enol content was taken from Ref. [187]...

Carbonyl-containing molecules, such as 1, with an a-carbon-hydrogen C(25p )-H(li) hybridized bond can exist as an enol tautomer 2, and their relative proportions depend on the relative stability of each tautomeric component (Scheme i)"4-i20 p j. saturated carbonyl-containing molecules, like 1, the amount of enol content 2 is quite low (<1% ... 

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