*3.3. Enaminones and Similar Compounds*

Data from the simple compounds such as those of Figure 9 may serve as reference points for more complex systems such as those of phenylene diamine derivatives of dehydracetic acid (Figure 10) [28]. The isotope effects in A are line with a non-tautomeric system, whereas those of B can only be explained by assuming a tautomeric equilibrium.

**Figure 9.** Deuterim isotope effects on 13C chemical shifts. \* The central line is broad, so no isotope effect could be measured. \*\* Assignment tentative. Reprinted with permission from Ref. [29]. Copyright 2019 Elsevier.

**Figure 10.** Two-bond deuterium isotope effects on 13C chemical shifts in ppm of phenylenediamine derivatives of dehydracetic acid deuterated. (**A**) Derivative based on *o-*phenylene diamine; (**B**) Derivative based on m-phenylene diamine Data from Ref. [28].

Isotope effects have been measured in 1,4-dihydropyridines (Figure 11). The finding that the deuterium isotope effects on 13C chemical shifts are very similar in derivatives A and B [30] seems to show that the potential hydrogen bonding in B is weak.

**Figure 11.** Two-bond deuterium isotope effects on 13C chemical shifts of 1,4-dihydropyridines. (**A**) Without intra-molecualr hydrogen bond; (**B**) with intramolecular hydrogen bond From Ref. [30].

## *3.4. Dimers and Trimers*

Tolstoy et al. in a very elegant way have used isotope effects on chemical shifts to determine the size of self-associated dimethylphosphinic, diphenylphosphoric acid, phenylphosphinic acid and bis(2,4,4-trimethylpentyl)phosphinic acid [31]. This has been extended to investigate heterodimers and heterotrimers of phosphinic and phosphoric acids (see Figure 12) [32]. Using the same technique, it could be proven that dimethylarsenic acid forms cyclic dimers in solution with two equivalent strong hydrogen bonds [33].

**Figure 12.** High-frequency part of the 1H NMR spectrum of partially deuterated (OH/OD, 57%D) of a mixture of diphenylphosphoric and dimethylphospinic acid in CDF3/CDF2Cl at 100 K. Trimers are marked with asterisks and dimers with diamonds. Reprinted from Ref. [32].

## *3.5. Miscellaneous*

The equilibrium in the system shown in Figure 13 was originally determined using deuterium isotope perturbation techniques [34] and later calculated [35]. Xu et al. [36] investigated the similar system, 2,4-dihydroxybenzaldehyde measuring integrals and found that the deuterium prefers the non-hydrogen-bonded bond OH-4. O´Leary [37] analyzed the 2,6-dihydroxybanzaldehyde system in terms of vibrations and found that the highfrequency modes resulted in a Keq less than one, whereas the low- and medium-frequency modes resulted in a Keq > 1.

**Figure 13.** Equilibrium between monodeuterated 2,6-dihydroxyacylaromatics. X=H, CH3 or OCH3.

Deuterium isotope effects at C-2 at 1,1,1,3,3,3-hexafluoro-2-propanol-d2 have been investigated in CDCl3 and trimethylamine. The isotope effects were 0.364 and 0.341 ppm, respectively [38]. The authors ascribed the difference to complex formation, but the difference is very small and if anything in the wrong direction.

Schulz et al. [39] studied primary isotope effects in 1-N-TMPH-CH2-2[HB(C6F5)2]C6H4 (NHHB) (Figure 14). The molecule shows a strong dihydrogen bond. Deuteration of the NH proton led to a primary deuterium isotope effect of 0.56 ppm, whereas deuteration of the BH hydrogen did not lead to an isotope effect. The isotope effect of 0.56 ppm could indicate a double-well hydrogen bond potential [40]. However, the authors argued for a single-well potential, but they did not explain why the other effect was zero.

**Figure 14.** Structure of NHHB. The two hydrogens of the dihydrogen bond are selectively deuterated. From Ref. [39].

A xenon molecule in a deuterated hydrogen bond network of β-hydroquinones crystal shows an isotope effect of 2.4\* ppm at 298 K and 2.6 ppm at 333 K. This effect is rather small considering the chemical shift range of Xe [41]. The effect is similar to that found in water/heavy water of 3.92\* ppm. CH3OD gives an isotope effect of the opposite sign.
