Deuterium isotope effects, chemical shifts equilibrium

The measurement of deuterium isotope effects on chemical shifts is a useful tool for studies of tautomeric equilibrium (for details see the reviews 42 44). The deuterium isotope effect AX(D) is defined as the difference between chemical shifts in deuterated and non-deuterated sample [26]. 

The deuterium isotope effects on chemical shift consists of intrinsic isotope effect (direct perturbation of the shielding of X atom) and equilibrium isotope effect (perturbation of the equilibrium caused by the isotopic substitution). The values of deuterium isotope effects are to some extent independent of chemical shifts and allow determination of the mole fraction of the forms in equilibrium. 

T. Deuterium isotope effects on 13 C chemical shifts In the studies of proton transfer equilibrium of Schiff bases, the most informative are deuterium isotope effects measured for carbons bonded with proton donor groups (C-2 or C-7 for gossypol derivatives). For imines in which... 

The position of the proton transfer equilibrium for the Schiff bases being derivatives of rac-2-aminobutane [24] or rac-a-methylbenzylamine [25] and their adducts with dirhodium complex has been estimated in CDCI3 solution on the basis of measurements of deuterium isotope effects on 15N chemical shift.12 It was shown that adduct formation significantly influenced the position of the equilibrium which was manifested by AN(D) values. 

T. Dziembowska, Z. Rozwadowski, Application of the deuterium isotope effect on nmr chemical shift to study proton transfer equilibrium. Curr. Org. Chem. 5, 289-313 (2001)... 

The tautomeric equilibrium of these has been described by several methods, i.e. couplings , J(N,H) coupling constants" and deuterium isotope effects on Qiis.iie and N chemical shifts as these are very different for the azo and hydrazo forms . Isotope effects on F chemical shifts are very sensitive due to the large chemical shift range (and, more importantly, the large difference in chemical shifts of the two tautomeric forms) ". 

The equilibrium of Schiff bases (48) has been studied in detail because of their interesting properties both in the solid state (Section II.N) and in biological reactions. This can be done as just described for o-hydroxy azo compounds ( 7(N,H) coupling constants and deuterium isotope effects on C and N chemical shifts)Based on /(N,H) it could be concluded that the Schiff bases form a conventional tautomeric equilibrium that can be described by two species. ... 

R75 T. Dziembowska and Z. Rozwadowski, Application of the Deuterium Isotope Effect on NMR Chemical Shift to Study Proton Transfer Equilibrium , p. 289... 

The tautomeric equilibria of 2-pyridoyl-, 3-pyridoyl-, and 4-pyridoyl benzoyl p-diketones in the liquid and solid state have been determined by Hansen et al. by the use of deuterium isotope effects on H and NMR chemical shifts and spin-spin/hc couplings. In particular, the two-bond and three-bond experimental and calculated /hc couplings have been applied to confirm the equilibrium positions in the solution state. 

Figure 6.17 Deuterium isotope effects on C chemical shifts (in parts per billion) illustrating static structures (first and last) and an equilibrium structure in the middle.

Schiff bases are important molecules also in biological contexts. Schifif bases of ortho-hydroxy type (Figure 6.26) represent both static and tautomeric cases. Primary deuterium isotope effects are small in a static case. For tautomeric systems, the primary deuterium isotope effects on chemical shifts are temperature dependent [50]. This was also investigated in detail for a series of Schiff bases (X = 4-methoxy, 5-methoxy, and 4,6-dimethoxyphenyl of Figure 6.26). These have been studied in detail using secondary isotope effects on chemical shifts. One approach is the simple one presented in Eq. (6.1). The other one is based on the Limbach approach [40]. The presence of an equilibrium is established in many of these Schiff bases. A... 

Figure 3.12 Equilibrium deuterium isotope effects on C chemical shifts of p-diketones as a function of the mole fraction. (Reproduced from Bordner et al. [21]. Copyright (1989), with permission of Wiley-VCH.)...

These are most often deuterium isotope effects, - A(D) meaning that both and (often called D) resonances are observed and subtracted to give the isotope effects. Primary isotope effects on chemical shifts can again be divided into intrinsic and equilibrium isotope effects. The intrinsic ones are observed in systems like... 

The aforementioned was based on data for which both heavy atoms were the same. If this was not the case, large negative primary isotope effects may have been found for double well potential cases. An example is P-thioxoketones [3]. A case in which the heave atoms are the same and the double well potential is nonsymmetrical is seen in the enol form of 2-acetylcyclohexanone (Figure 3.13). The difference between the OH proton chemical shifts of the two tautomers can be calculated as 1 ppm. As discussed in the section on deuterium isotope effects on chemical shifts the change upon deuteriation is 3%, which means that the equilibrium contribution to the primary isotope effect is approximately 0.03 ppm or in other words close to negligible. 

The upheld shift of the peak of the perturbed protons is temperature-dependent and varies between 0.215 ppm at — 105°C and 0.146 at — 43°C (Saunders and Kates, 1983). The equilibrium constant for the stereospecihc hydride shift (K = 1.28-1.18 between — 105°C and — 43°C) can be calculated using the modihed equation = (A -I- 28)/(A — 28), (Sorensen and Ran-ganayakulu, 1984). The same equilibrium constants within experimental error were obtained for the complementary isotope effect on the proton chemical shift in the decadeuteriated cation (C7DioH ) and for the isotope effect on the deuterium chemical shift in the monodeuteriated cation (C,HioD. ... 

Deuterium isotope on cbemical sbifts is very suitable for the investigation of equilibrium isotope effects because of the large CS difference between the C-N and the C=N nitrogen. The chemical shift difference is estimated to be 100-140 ppm [40]. 

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