Tautomeric prototropic equilibrium

About 90% of all the studies on tautomerism refer to the determination of prototropic equilibrium constants in solution. Most probably in the next years there will be further studies in the remaining areas, some of them almost a desert at the present time. 

This prototropic equilibrium has been also studied in substrates bearing metals linked to the nitrogen atom in the form of CP2MCI or CpMCl2 groups [76-78], and the influence of different ligands at the metal center on the resulting equilibrium between the kinetically favored NH phosphinous amide and the thermodynamically stable tautomeric PH phosphazene form has been discussed (Scheme 11). 

Perhydropyrido[ 1,2-a]pyrimidin-2-one 305 exhibits prototropic equilibrium and ring-chain tautomerism (92AP177). In methanol -d4 hexadeuter-ated bicyclic compounds were formed. 

Photoelectron spectra of 2-, 3- and 4-mercaptopyridines and fixed structure models have been measured for evaluation of tautomeric populations. Whereas for 3- and 4-mercaptopyridine a great predominance of the mercapto form in vapor phase is demonstrated, 2-mercaptopyridine shows the existence of a prototropic equilibrium between the mercapto and thioxo forms. From the integration of band areas it follows that there is about 10% of the thioxo form in the equilibrium (77JCS(P2)1652, 79TL2585). 3-Formyl-2-mercaptopyridine was found to exist in the gas phase as a tautomeric mixture containing about 16% of the thione form (81T2663). 

The stability of the pyrazolinone tautomers was related to their scale of aromaticity.Experimental values for the tautomerism of pyrazolinone derivatives were obtained by flash vacuum pyrolysis (FVP), which allowed the calculation of the effect of the temperature on the equilibrium between tautomers. The variation of Kj with the temperature was determined by H NMR in solution for the model compound l-phenyl-3-methyl-2-pyrazolin-5-one (Scheme 25), showing that at 0 K the only tautomers present are either the NH or the OH ones. Temperature and solvent effects on the prototropic equilibrium of the model compound in solution showed that... 

Prototropic tautomerism differs from all other types (methyltropy, metallotropy, acylotropy, halogenotropy, etc.) because the proton is very small, and therefore insensitive to steric effects, and also that it forms hydrogen bonds (HBs), which can considerably affect both the equilibrium and the rate of the process. 

Annular prototropic tautomerism of 1,2,4-triazoles (s-triazoles) involves an equilibrium between three possible forms (26a-26c) (Scheme 13). 

Prototropic tautomerism of 2-alkylated tetrahydro species 21 is solvent dependent, tautomers 21a and 21b being identified as the major species present in DMSO-dimethyl sulfoxide) and deuterochloroform, respectively <2000HCA1693> by NOE experiments. Acetylated analogue 22 appears to behave similarly, although in this case the spectrum is complicated by the presence of amide rotamers. As judged from the N-H signals observed in H NMR spectrum, the major species in deuterochloroform is 22a, whereas, in DMSO-i4> the tautomeric equilibrium constant approaches unity, and both tautomers are present. 

The existence of a tautomeric equilibrium involving prototropic, ring-chain tautomerism was established on the basis of the u.v., i.r., and 1 H-n.m.r. spectra of the synthetic compounds 55 and 56. 

Prototropic tautomerism - This refers to an equilibrium between two or more constitutional isomers that occurs by migration of a proton from one atom to another <2000AHC(76)1 >. For examples see Sections 2.2.5.1.1, 2.3.5.1, and 24.5.1.1. 

Thiazoles bearing hydroxy, thio, or amino groups at C-2, C, or C-5 are in tautomeric equilibrium with the corresponding oxo, thioxo, or imino thiazolines. Thiazoles bearing more than one of these groups also display similar prototropic tautomerism, although with some restrictions. 

In the presence of a second ionogenic group having a basic character, a prototropic tautomeric equilibrium is observed between the neutral 93 and the zwitterionic 94 forms (equation 37). 

In N-unsubstituted unfunctionalized derivatives 1, annular prototropic tautomerism has been studied using interpolation methods based on C-NMR chemical shifts and H-NMR coupling constants (82JOC536). Tautomers A and B are in equilibrium in DMSO solution, while C and D tautomers are not present (Section II,A,4,a) (65CI(L)182 82JOC536). In compounds in which R R the tautomeric equilibrium is shifted toward the A form, R being the less bulky substituent. 

Imidazoles and benzimidazoles unsubstituted on nitrogen exhibit fast prototropic tautomerism which leads to equilibrium mixtures of unsymmetrically substituted compounds, for example, 4(5)-substituted imidazoles, 4(7)- or 5(6)-substituted benzimidazoles. The proton exchange is an intermolecular process (which may involve a protic solvent), and is so fast on the NMR time scale that only one species is usually apparent in the spectrum. iV-Substituted azoles cannot exhibit such tautomerism, and strongly acidic media also inhibit proton exchange. Much work since the mid-1980s has focussed on determination of the proportions of isomers in tautomeric mixtures, with theoretical studies applied to the gas phase (and solution), and solid state studies are also receiving considerable attention. Extrapolation of the results of gas phase and solid state studies to solution, though, can only be less than perfect. 

Prototropic tautomerism of 4(l//)-quinolone-3-carboxylic acid derivatives 25 has been studied with particular emphasis on the influence of the ring substituents on the equilibrium. The techniques used include UV, H-NMR, 13C-NMR (solution), and 13C-NMR CP/MAS (solid state) (92T6135). 

The prototropic tautomerism of compounds containing an amidine moiety has been studied extensively.41-43 However, the data obtained on this type of equilibrium are rather qualitative and have not been explored systematically. The difficulties encountered in this work stem primarily from the common experience that proton transfer between electronegative atoms, such as nitrogen, is very fast.43,44... 

This ready nucleophilic substitution is surprising, since in the normal tautomeric form 18 the 6-position should be deactivated towards nucleophilic attack indeed, as discussed in Section VIII, this position is a site where electrophilic substitution takes place readily. It is possible that in the presence of base prototropic rearrangement via the dihydrodiazepenide anion 19 to the tautomer 20 takes place. Although the equilibrium concentration of 20 is likely to be very small it would be strongly electrophilic at the 6-position owing to the effects of the bromine atom and the two azomethine groups, and it could well be the reactive species in the nucleophilic substitution of the bromine atom. A tautomer of this structure... 

Isomerizations in which an H-atom changes its position in a heterocyclic system are known as annular tautomerisms. This is a special case of prototropy (prototropic rearrangement) [57]. For isoindole, the position of the equilibrium depends to a large extent on the type of the substituent in the 1- and/or 3-position [58]. The 1-phenyl compound exists in the 2//-form and couples with benzenediazonium chloride in the 3-position. 

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