2.4.3. Primary Isotope Effects

<sup>P</sup>Δ1H(ND), and <sup>P</sup>Δ1H(NT), in which the NH is replaced by either deuterium or tritium may also be used to gauge intramolecular hydrogen bonding. Only a few examples are available [84].

Protonated DMAN's (DMANH+) (Figure 2) show tautomerism. However, for symmetric compounds this will not influence the primary isotope effects [56]. For DMANH+ itself the <sup>P</sup>Δ1H(ND), is 0.69 ppm. Similar values were found for a 4,5-CH2OCH2 derivative as well as the one in which the methyl groups are changed to ethyl groups. However, for 2,7- substituted derivatives the values are much smaller, dichloro, dibromo, bisdimethylamino, dimethoxy and ditrimethylsilyl gave values of 0.30, 0.23, 0.34, 0.31 and 0.14 ppm. [85] The much smaller values in these derivatives were ascribed to a buttressing effect leading to a shorter N ... N distance [86]. These data and more together with data from Ref. [84] are plotted in Figure 24. Interesting points falling in-between at chemical shifts 14.03 and 14.84 ppm are N-phenyl derivatives, so these chemical shifts must be corrected for ring current effects. Others are also N-phenyl derivatives, but substituted in the 2-position so the rings are twisted heavily out of the double bond plane and thereby reducing the ring-current effects. The primary isotope effects were also related to IR isotope ratios [73].

**Figure 24.** Plot of primary deuterium isotope effects vs. NH chemical shifts. Data from [56,85].

As the review deals with NH hydrogen bonds the obvious isotope to use is deuterium. Secondary deuterium isotope effects over two-bonds tell in a qualitative way about the hydrogen bond strength. The larger the isotope effect, the stronger the hydrogen bond. For a relation to hydrogen bond energy see Section 3. In case of one bond deuterium isotope effects on 15N two different scenarios are found. In RAHB cases the isotope effect increases with increasing hydrogen bond strength, whereas for intramolecular hydrogen bond cases with no direct connection between donor and acceptor (like in DNA) the magnitude of the isotope effect decreases as the distance between heavy atoms decreases.

The primary isotope effects deuterium isotope effects show a more irregular behavior. It would be interesting in the future to compare primary isotope effects for the systems shown above with the one bond secondary isotope effects on 15N.
