A Theoretical Evaluation of the pK_HBand Δ$H{{{\,\ominus}\hfill \atop {\rm HB}\hfill}}}$ Hydrogen‐Bond Scales of Nitrogen Bases

Abstract

The experimental pKHB hydrogen-bond (HB) basicity scale and the corresponding DeltaH[symbol: see text]HB enthalpic scale of nitrogen compounds are extended and analysed in light of simple theoretical descriptors using the B3LYP density functional method and a medium-size basis set (6-31+G(d,p)).The selected training set includes 59 monofunctional unhindered nitrogen bases for which homogeneous and accurate experimental pKHB and DeltaH[symbol: see text]HB data have been determined by means of the association equilibrium of the bases with a reference hydrogen-bond acid, 4-fluorophenol, in CCl4. The three hybridisation states encountered in the nitrogen atom, sp, sp2 and sp3, are equally represented in this data set. A proper estimation of their experimental enthalpy (DeltaH[symbol: see text]HB) is directly attainable from the theoretical enthalpy of the complexation reaction with hydrogen fluoride (DeltaH[symbol: see text](HF)). However, a second parameter is required to calculate with good accuracy the experimental free energy of association represented by pKHB. About 99% of the variance of the pKHB scale is described by a bilinear equation using the minimum electrostatic potential (Vs,min) of the monomer in addition to the interaction energy (D0(HF). The equations are tested for an external set of 99 additional compounds including very different nitrogen bases such as ortho-substituted pyridines, polyazines and azoles.Theoretical calculations give a reliable estimation of hydrogen-bond basicity provided that the populations of the different isomers of the bases are taken into account by using the Boltzmann law, and that a specific halogen-bond interaction with the solvent CCl4 is considered for polybasic molecules.The pKHB scale can thus be extended to important classes of species experimentally inaccessible in CCl4, to polynitrogen compounds and to molecules of biological significance.

Hydrogen‐Bond Accepting Strength of Five‐Membered N‐Heterocycles:The Case of Substituted Phenylpyrrolines and Myosmines

“…[18] Hence, the data in Table 1 is limited to the experimental and/or calculated pK BHX values of a few diverse five-membered N-heterocyclic compounds. The basicity range of these compounds appears to be extremely large because the nitrogen atoms belong to very different families depending on the number and positions of the double bonds.…”

“…This loss of basicity, in line with the diminution of p character, has been attributed to a reduction of the charge transfer between the nitrogen lone-pair and the anti-bonding XH orbital of the HB donor. [18] The nitrogen basicity of 3-pyrroline (14) is only slightly weakened by the [18] [d] Ref. [24] [e] Ref.…”

“…These methods involve (i) experimental ∆ν(OH) frequency shifts, [11,12] (ii) substituent effects, [13,14] (iii) molecular fragment models [15] or (iv) theoretical descriptors. [12,16,17] In a recent paper [18] we set up an equation based on theoretical descriptors computed at the B3LYP/6-31+G(d,p) level of theory aimed at calculating the equilibrium constant of pFP association with a nitrogen atom in carbon tetrachloride [Equation (4)]. In this equation, V s,min is the local minimum electrostatic potential value at the molecular surface of the monomeric base and D 0 (HF) is the variation of the electronic energy of the model association equilibrium between hydrogen fluoride and the base [equilibrium (5)], corrected from the zero-point vibrational energy.…”

“…[18] First, for flexible monomers, the D 0 (HF) and V s,min parameters of each isomer must be calculated and weighted according to their Boltzmann population. Secondly, the solvent-base halogen-bond interaction must be explicitly taken into account when the base possesses a significant second basic site B 2 so that Equation (5) is replaced by Equations (6) and (7) for the calculations of dibasic B 1 ϽϾB 2 compounds.…”

Structural Features and Hydrogen‐Bond Properties of Galanthamine and Codeine: An Experimental and Theoretical Study

“…Thus, theoretical calculations must take into account the flexibility of the monomer to gain a better insight into the structural dependence of the HB basicity. In recent works, [22,67] we have shown that a weighting of the electrostatic potentials or interaction energies by Boltzmann populations provides satisfactory descriptions of the experimental HB basicities.…”