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.

[1]  C. Altona,et al.  Vicinal proton−proton constants. I: Formulation of an equation including interactions between substituents , 1989 .

[2]  K. Pachler.  Extended hückel theory MO calculations of proton-proton coupling constants—II , 1971 .

[3]  F. D. Leeuw,et al.  The relationship between proton-proton NMR coupling constants and substituent electronegativities—I : An empirical generalization of the karplus equation , 1980 .

[4]  J. Eisinger,et al.  Synthetic spectroscopic models related to coenzymes and base pairs. II. Evidence for intramolecular base-base interactions in dinucleotide analog. , 1968, Journal of the American Chemical Society.

[5]  K. Pachler.  The functional form of the karplus equation , 1972 .

[6]  Cornelis Altona,et al.  Relationship between protonproton NMR coupling constants and substituent electronegativities. V —Empirical substituent constants deduced from ethanes and propanes , 1989 .

[7]  F. D. Leeuw,et al.  Calculation of NMR spin-spin coupling constants using the extended Hueckel molecular orbital method , 1984 .

[8]  M. Barfield,et al.  Solvent dependence of nuclear spin-spin coupling constants , 1973 .

[9]  M. Huggins.  Bond Energies and Polarities1 , 1953 .

[10]  S. Beaucage,et al.  Fluoride ion catalyzed alkylation of nucleic acid derivatives using trialkyl phosphates, dialkyl sulfates and alkyl methanesulfonates. , 1979, Nucleic acids research.

[11]  Kirby,et al.  [Reactivity and Structure Concepts in Organic Chemistry] The Anomeric Effect and Related Stereoelectronic Effects at Oxygen Volume 15 || References , 1983 .

[12]  Cornelis Altona,et al.  Relationship between proton—proton NMR coupling constants and substituent electronegativities. IV —An extended karplus equation accounting for interactions between substituents and its application to coupling constant data calculated by the Extended Hückel method , 1989 .

[13]  T. Tanabe,et al.  The ethylation of nucleic acid-bases with triethyl phosphate. , 1977 .