Prototropic tautomers

Theoretical aspects of the study of prototropic tautomers by mass spectrometry... 

Four prototropic tautomers are possible for unsubstituted 2,4-dimereap-toimidazole. In the absence of detailed studies, the thiol-thione form 223b is eonsidered to be the major tautomer (Seheme 75) [720C2423 76AHC (SI), p. 457 84CHEC-I(5)345]. 

Among the structural types that are within the scope of this review are many heterocyclic A-oxides, A-imides and A-ylides (e.g., 36). The chemistry of these systems, which is extensive, has already been the subject of comprehensive reviews " and a discussion of their chemistry is not included here. Similarly the structure and chemistry of prototropic tautomers has also been reviewed recently and will not be duplicated here. 

There is a growing interest in the use of 15N NMR spectroscopy for elucidation of various structural problems of azole chemistry, especially tautomerism. For example, the mole fractions of the prototropic tautomers were obtained from the 15N chemical shifts of the NH tautomers and the corresponding N-methyl derivatives. By this method, the average mole fraction for the 2-NH tautomer of benzotriazole is 0.02 in both CDC13 and DMSO, and that of 1,2,3-triazole is 0.34 in CDC13 and 0.55 in DMSO (82JOC5132). 

Proton transfer (PT), i.e., the kinetic aspects of heteroaromatic prototropic tautom-erism, is an important and somewhat neglected topic or, at least, much less studied than the thermodynamic aspects (equilibrium constants, acidity, basicity, pK, etc.). Intermolecular proton transfer between two heterocycles, one protonated and one neutral, occurs along a hydrogen bond (see Sect. 3.5). When the proton transfer occurs in a crystal or in an amorphous solid, we speak of SSPT (vide supra). 

Some Electronic Properties of Prototropic Tautomers of 8-Azapurine... 

Annular tautomers - Annular tautomers are prototropic tautomers (see below) in which the migrating proton is restricted to ring atoms. For examples see Sections 2.3.5.1.1, 2.4.5.1.1, and 2.5.5.1. 

Desmotropes - Desmotropes are prototropic tautomers in which both tautomeric forms have been isolated. They should not be confused with polymorphs in which the same molecule (tautomer) crystallizes in two or more crystal forms <2008SSNMR68>. For examples see Sections 2.4.34 and 24.5.1.1. 

Introduction. Annular tautomers are prototropic tautomers in which the migrating proton is restricted to ring atoms, which for azoles are usually nitrogen atoms, e.g., 239 240 and 241 242. For unsubstituted pyrazole 239 (R = R2 = H) and imidazole 241 (R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles the unsubstituted rings can occur as two distinct tautomers. However, interconversion occurs readily and such tautomers cannot usually be separated. In rare examples where prototropic tautomers can be separated as discrete crystal forms they are referred to as desmotropes, e.g., isomers 147 and 148 (Section 2.4.3.4). Further examples of desmotropes are 3-methyl-4-nitropyrazole 239 (R1 = N02, R2 = Me) and 5-methyl-4-nitropyrazole 240 (R1 = N02, R2 = Me) <1994CC1143>. 

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