Annular Prototropic Tautomerism

The annular prototropic tautomerism of the parent 1,2,3-triazole and benzotriazole are described in CHEC-I 84CHEC-I(5)691 and was reviewed earlier 76AHCS295 . 

Method 113-triazole over 2H-triazole IH-benzotriazole over 2 H-benzotriazole -Me2NCH2Bt over 2-Me2NCH2Bt 

Calculations at the 6-3IG level indicate that in the gas phase, 2//-l,2,3-triazole is more stable than 1//-1,2,3-triazole by about 4.5 kcal moC. In solution, the IH isomer becomes the more stable species because the large difference in dipole moments favors the more polar tautomer. The triazolium ion (75) is predicted to be more stable than (76) by about 13.5 kcal mol 89Mi40i-0i . 2//-1,2,3-Triazole represents more than 99.9% of the equilibrium mixture in the gas phase. However, the ab initio calculated proton affinity of 1//-benzotriazole is 10.2 kcal mol larger than that of 2//-benzotriazole, which is consistent with ICR measurements (1-methylbenzotriazole is 10 kcal mol more basic than 2-methylbenzotriazole). Measurements of enthalpies of solution, vaporization, sublimation and solvation in water, methanol and DMSO confirm the predominance of the IH tautomer in solution 89JA7348 . The energy difference between the tautomers of 1,2,3-triazole has also been estimated at the 6-31G (MP2)//3-21G level including zero-point effects. The 

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

Four pairwise degenerate tautomeric forms referred to as the IH (27a and 27d) and IH (27b and 27c) tautomers are needed to describe the annular prototropic tautomerism of unsubstituted tetrazole 27 (R = H) (Scheme 14). 

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. 

An account of non-prototropic tautomerism (mainly annular metallotropy) and nonaromatic functional tautomerism will also be included. 

A well-known example of non-prototropic tautomerism is that of azolides (acylotropy). The acyl group migrates between the different heteroatoms and the most stable isomer (annular or functional) is obtained after equilibration. In indazoles both isomers are formed, but 2-acyl derivatives readily isomerize to the 1-substituted isomer. The first order kinetics of this isomerization have been studied by NMR spectroscopy (74TL4421). The same publication described an experiment (Scheme 8) that demonstrated the intermolecular character of the process, which has been called a dissociation-recombination process. 

Boiling points and melting points are considered from the point of view of intermolecular forces between the molecules, together with solubilities and chromatographic behavior, both gas and liquid chromatography. The topic of aromaticity and stability in general is covered as befits its importance. Conformations, particularly of the cyclic non-planar compounds, are dealt with. A section on tautomerism covers both prototropic tautomerism (annular and of substituents) and ring-chain tautomerism. 

Six-six condensed heterocyclic systems without a tautomeric functional group(s) [for instance, pteridine 135 (R = R2 = R4 = H)], do not exhibit prototropic tautomerism. The introduction of an oxo(thioxo)- and/or amino group(s) into the pteridine system, and the appearance of at least one NH group in the ring, leads to functional and/or annular tautomerism. Pteridine is formally the parent of three groups of compounds of particular interest because of their biological importance pterins (136), lumazines (137), and flavins (138). 

The two possible forms of prototropic tautomerism, annular and ring-substituent, have been described in 1,2,6-thiadiazine 1,1-dioxide derivatives. Studies have been mainly carried out by H, C, N, and UV spectroscopy in DMSO and water and by X-ray analysis in the solid state. 

The C spectrum (15.04 MHz) of perimidine (13 R = H) (Table 1) is consistent with a symmetrical structure, reflecting rapid prototropic tautomerism between the annular nitrogen atoms as found for H NMR. Tautomerism is excluded in 1-alkyl derivatives as shown for (13 R = Me) in Table 1. The relative C chemical shifts parallel those of the corresponding protons in the H NMR spectrum. The relative order of the chemical shifts in C NMR of 1,8-naphthalenediamine is the same as in perimidine. All carbocyclic peaks other than C9b exhibit a pronounced upfield shift, in accord with the 7r-excessive character of the carbocyclic rings in the perimidine system. On the other hand, C2... 

Scheme 13.3 Prototropic tautomerism in organic compounds (a) annular tautomerism in pyrazoles functional tautomerism in (b) pyrazolines [47] and (c) Schiff bases [48],...

Annular tautomers are prototropic tautomers in which the migrating proton is restricted to ring atoms. For these five-membered heterocycles, annular tautomerism can only occur with pyrrole 2 and its polycyclic derivatives. There is no authenticated case of the monocyclic pyrrolenine tautomeric forms 211 and 212 predominating, presumably due to the required loss of resonance energy in these nonaromatic tautomers . 

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