Proton-shift tautomerism, also

When the lone electron pair is protonated, the nitrogen chemical shift moves by ca. 100 p.p.m, to higher field. Large upheld shifts are also found when a compound exists in a tautomeric form with a proton on the nitrogen. The nitrogen NMR spectrum is often of considerable value in studies of tautomerism of this type. 

DNA bases can undergo proton shifts while forming various tautomers. Studies of tautomerism in the gas phase can show the relative stabihties of the individual tautomers. However, a bulk solvent and also a microhydrated environment can change the relative stabilities substantially. 

A-heterocyclic carbenes (NHC) are also efficient organocatalytic tools for generating homoenolate equivalents from a,P-unsaturated aldehydes. These reactive intermediates display a versatile reactivity in a number of catalytic transformations attesting to an important synthetic potential [38]. Recently, Scheldt et al. [39a] accomplished the first enantioselective protonation of a homoenolate species generated by a chiral NHC precursor 93 in the presence of DIE A and an excess of ethanol as the achiral proton source (Scheme 3.46). The suggested mechanism involves an initial addition of NHC 93 to the enal 89 followed by a formal 1,2-proton shift resulting in the formation of the chiral homoenolate equivalent 91. A diastereose-lective P-protonation/tautomerization sequence leads to the acyl triazolinium inter-... 

Clearly, in the case of (66) two amide tautomers (72) and (73) are possible, but if both hydroxyl protons tautomerize to the nitrogen atoms one amide bond then becomes formally cross-conjugated and its normal resonance stabilization is not developed (c/. 74). Indeed, part of the driving force for the reactions may come from this feature, since once the cycloaddition (of 72 or 73) has occurred the double bond shift results in an intermediate imidic acid which should rapidly tautomerize. In addition, literature precedent suggests that betaines such as (74) may also be present and clearly this opens avenues for alternative mechanistic pathways. 

In the case of the 7-hydroxy-substituted compounds 44 (Scheme 2), 54 different derivatives were investigated by 13C NMR spectroscopy and, in some cases, also by 1SN NMR spectroscopy <1995JST(335)273>. With the help of proton-coupled 13C NMR spectra, semi-selective INEPT (insensitive nuclei enhanced by polarization transfer) experiments, and heteronuclear multiple bond correlation (HMBC) two-dimensional 2D-NMR spectra, all shifts could be unequivocally assigned. While the C-7 shifts did not allow the existing tautomeric situation to be determined, a clear decision could be made by H NMR spectroscopy in this respect. The 1SN NMR spectra revealed an equilibrium between the N(4)H and N(3)H tautomeric forms, which is fast on the NMR timescale. 

This has been further confirmed by N NMR spectra which indicate >95 /o of the 5-one form with the tautomeric proton bonded to the N-4 atom (85MRC166,86BCJ3263). The C NMR shift of C-5 in structure (4 R = H) also confirms the tetrazolinone form, being about 148-149 ppm for X = O and about 163-165 ppm for X = S in agreement with 1,4-disubstituted model compounds... 

C NMR studies, especially in the solid state (83H(20)1713), are of value in studies of tautomerism (83H(20)1713, 86ZC378). Solid state studies on imidazole (and pyrazole) show there are three distinct signals for the annular carbon atoms (imidazole C-2, 136.3 C-4, 126.8 C-5, 115.3 ppm). Proton exchange does not occur in the solid, hence the compounds resemble their crystal structures. Comparison with the corresponding chemical shifts for 1-methylimidazole (137.6, 129.3, 119.7 ppm) implies that the tautomerism has been frozen in the solid state (81CC1207). Solid-state examination of 2,2 -bis-lH-imidazole also reveals frozen tautomerism. 

The ring proton chemical shifts (8 values) of l,2,4-triazolo[l,5-a]pyrimi-dine derivatives are in the order H-7 > H-5 > H-2 > H-6 (64CPB204).The charge densities determined from proton chemical shifts showed a remarkably good correspondence with the charge distributions calculated by the simple Htlckel Molecular orbital (HMO) method (64CPB204). HMO calculations for all possible tautomeric forms of the isomeric triazolopyrimidin-5(7)-ones were also performed (88M341). 

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