Empirical group electronegativities for vicinal NMR proton-proton couplings along a CC bond: Solvent effects and reparameterization of the Haasnoot equation

Empirical group electronegativities (substituent parameters λi), valid for 3J(HH) in saturated HCCH fragments, were derived from the coupling to methyl in substituted ethanes and isopropyl derivatives according to the equation \documentclass{article}\pagestyle{empty}\begin{document}$$ \langle {}^3J({\rm{HH)}}\rangle = 7.660 - 0.596(\lambda _1 + \lambda _2) - 0.419(\lambda _1 \lambda _2) $$\end{document} In contrast to earlier work, it was found advantageous to differentiate between the λi values of hydrogen acting as substituent in CH3 as compared with H in CH2. Special attention was paid to solvent effects, in particular the influence of D2O, on the vicinal couplings and thus on λi. The previously derived λi values remain valid in all common organic solvents but a special effect of D2O on λ is manifest in cases where the α‐substituent carries one or two non‐conjugated lone pairs of electrons that readily act as hydrogen bond acceptors: Δλ= −0.11 ± 0.03 for NH2, NHR, NR2, OH, OR, R = alkyl. Protonation of NH2 to give NH3+ lowers λi by 0.28 units. The λi values for the nucleic acid bases (Ade, Gua, Ura, Thy, Cyt), as determined from the N‐isopropyl derivatives, are 0.56 ± 0.01 irrespective of the solvent. Secondary amides display similar values. The parameters of the Haasnoot equation, originally derived with the aid of a Pauling‐type electronegativity scale, were reoptimized on the basis of the present λi scale; the previous overall r.m.s. error of 0.48 Hz now drops to 0.36 Hz and separate parameterization of HCCH fragments with different substitution patterns appears to be no longer necessary.