Michel Berthelot

Halogen-bond geometry: a crystallographic database investigation of dihalogen complexes

X-ray crystal structures of 141 halogen-bonded complexes Y-X.B formed between homo- and heteronuclear dihalogens Cl(2), Br(2), I(2), IBr and ICl with O, S, Se, N, P and As Lewis bases show remarkable and constant geometrical features. The metrics of the halogen bond found in the gas phase for simple complexes [Legon (1999a). Angew Chem. Int. Ed. Eng. 38, 2686-2714] is supported (i). in the solid state, (ii). for new Lewis acids (I(2) and IBr), (iii). for new basic centers (Se, As and =N-) and (iv). for more complicated bases. The Y-X...B arrangement is more linear than the corresponding Y-H...B hydrogen bond and the axis of the Y-X molecule lies in the plane of the B lone pair(s), with a preference for the putative lone-pair direction within that plane. However, exceptions to this lone-pair rule are found for sterically hindered thiocarbonyl and selenocarbonyl bases. A bond-order model of the halogen bond correctly predicts the observed correlation between the shortening of the X...B distance and the lengthening, deltad(Y-X), of the Y-X bond. The expectation that the solid-state geometric parameters d(X...B) and deltad(Y-X) reflect the strength of the interaction is supported by their significant relationships with the solution thermodynamic parameters of Lewis acidity and basicity strength, such as the Gibbs energy of 1:1 complexation of Lewis bases with diiodine. This analysis of halogen-bonded complexes in the solid state reinforces the similarities already known to exist between hydrogen and halogen bonding.

The Diiodine Basicity Scale: Toward a General Halogen‐Bond Basicity Scale

The new diiodine basicity scale pK(BI2) is quasi-orthogonal to most known Lewis basicity scales (hydrogen-bond, dative-bond and cation basicity scales). The diiodine basicity falls in the sequence N>P≈Se>S>I≈O>Br>Cl>F for the iodine-bond acceptor atomic site and SbO≈NO≈AsO>SeO>PO>SO>C=O>-O->SO(2) or PS≫-S->C=S≫N=C=S for the functionality of oxygen or sulfur bases. Substituent effects are quantified through linear free energy relationships, which allow the calculation of individual complexation constants for each site of polybases and thus the classification of aromatic ethers as carbon π bases and of aromatic amines, thioethers and selenoethers as N, S and Se bases, respectively. The pK(BI2) values of nBu(3)N(+)-N(-)C≡N, 2-aminopyridine and 1,10-phenanthroline reveal a superbasic nitrile, a hydrogen-bond-assisted iodine bond and a two-centre iodine bond, respectively. The diiodine basicity scale is a general inorganic but family-dependent organic halogen-bond basicity scale because organic halogen-bond donors such as IC≡N and ICF(3) have a stronger electrostatic character than I(2). The family independence can be restored by the addition of an electrostatic parameter, either the experimental pK(BHX) hydrogen-bond basicity scale or the computed minimum electrostatic potential.

An Enthalpic Scale of Hydrogen-Bond Basicity. 4. Carbon π Bases, Oxygen Bases, and Miscellaneous Second-Row, Third-Row, and Fourth-Row Bases and a Survey of the 4-Fluorophenol Affinity Scale

The thermodynamics of the O-H...B hydrogen bond (HB) has been determined in CCl(4) by FTIR spectrometry for a wide variety of carbon pi bases, oxygen bases, and miscellaneous first- to fourth-row bases, using 4-fluorophenol as a reference hydrogen-bond donor (HBD). After inclusion of previously studied nitrogen, sulfur, and halogen bases, this 4-fluorophenol affinity scale contains 314 varied organic bases and ranges over 40 kJ mol(-1). The 4-fluorophenol affinity scale in CCl(4) is shown to be applicable to most HBDs in most media, provided a small family dependence is taken into account. The HB affinity orders are quantitatively established according to the atomic acceptor site or to its bearing functional group. A comprehensive survey of the influence of substituents on these affinity orders is then achieved, considering electronic and steric effects, as well as effects of vinylogy or iminology. Iminology is found to be more efficient than vinylogy for transmitting resonance effects. Steric effects are shown to be less important in HB affinity than in HB basicity since they mainly act on the HB entropy. The spatial proximity of two acceptor sites can favor complexation through three-center hydrogen bonds, leading to superhydrogen-bond bases on the affinity scale.

The Hydrogen‐Bond Basicity pKHB Scale of Peroxides and Ethers

Using 4-fluorophenol as a reference hydrogen-bond donor, equilibrium constants, Kf, for the formation of 1:1 hydrogen-bonded complexes have been obtained by FTIR spectrometry for 39 ethers of widely different structure (cyclic and acyclic ethers, crown ethers, glymes, acetals, orthoesters, and disiloxane) and 3 peroxides, in CCl4 at 298 K. The pKHB scale of monoethers extends from 1.44 for 2,3-diadamant-2-yloxirane to –0.53 for hexamethyldisiloxane. The main effects explaining the variation of the hydrogen-bond basicity of sp3 oxygen atoms are (i) the electron-withdrawing field-inductive effect [e.g. in (CF3)2CHOMe], (ii) the electron-withdrawing resonance effect (e.g. in EtOCH=CH2) (iii) the steric effect (e.g. in tBu2O), (iv) the lone-pair–lone-pair repulsion (e.g. in cyclic peroxides), and (v) the cyclization giving the basicity order: oxetane > tetrahydrofuran > tetrahydropyran > oxirane. A spectroscopic scale of hydrogen-bond basicity is constructed from the infrared frequency shift Δν(OH) of methanol hydrogen-bonded to peroxides and ethers. The thermodynamic pKHB scale does not correlate with the ν(OH) scale because of (i) statistical effects in polyethers and peroxides (ii) secondary hydrogen-bond acceptor sites (e.g. in benzyl ether), (iii) variations of the s character of oxygen lone pairs either by conjugation or cyclization, (iv) steric effects, (v) lone-pair–lone-pair repulsions, and (vi) anomeric effects. The ν(OH···O) band shape reveals two stereoisomeric complexes, the most stable being tetrahedral at the ether oxygen atom.

Stéréochimie de la liaison hydrogène sur le groupe carbonyle

Abstract The asymmetric shape or splitting of the ν(XH) or ν(XD) bands of OH(OD), NH, SH and CH proton donors hydrogen bonded to the carbonyl group of ketones, aldehydes, esters, amides, ureas and carbamates have been explained by the existence of two stereoisomeric complexes: a linear complex (along the axis of the carbonyl bond) and an angular complex (in the direction of a lone pair). Bulky substituents on the carbonyl group or near the XH bond destabilize the angular arrangement. Inductive electron-withdrawing substituents on the carbonyl group favour the linear arrangement.

Basicity of azoles: complexes of diiodine with imidazoles, pyrazoles and triazoles

The diiodine basicity (a soft Lewis basicity) of 15 azoles (imidazoles, pyrazoles and triazoles) was measured by means of the formation constant of the diiodine–azole complexes in heptane at 298 K. The preferred sites of diiodine fixation are the nitrogens N-3 in imidazoles, N-2 in pyrazoles and N-4 in 1,2,4-triazoles. The diiodine basicity decreases with (i) the number of ring nitrogens, (ii) benzofusion, (iii) field electron-withdrawing effects of substituents on N-1 and (iv) for pyrazoles only, steric effect of substituents on N-1. In imidazoles and 1,2,4-triazoles, the lengthening and branching of alkyl groups on N-1 increase significantly the basicity, and 1-(adamant-1-yl)imidazole is the most basic of the azoles studied.

Partition coefficients and intramolecular hydrogen bonding. 1. The hydrogen-bond basicity of intramolecular hydrogen-bonded heteroatoms

Measurements were made in CCl4 of the formation constant KHB of the 1:1 hydrogen-bonded complexes between the reference donor 4-fluorophenol and the intramolecular hydrogen-bonded systems I (one lone pair on heteroatom Y, one intramolecular hydrogen bond: 8-hydroxyquinaldine and 2-(2-hydroxyphenyl)benzoxazole); II: (two lone pairs, two intramolecular hydrogen bonds: 2,2′-dihydroxybenzophenone and 1,8-dihydroxyanthrone) and III (two lone pairs, one intramolecular hydrogen bond: tropolone, salicylic acid derivatives and guaiacol). The pKHB values and the structural vibrational studies show that system I has a non-zero hydrogen-bond basicity which is due to the oxygen atom. In system II the non-zero basicity is explained by the two oxygens and the breaking of one intramolecular hydrogen bond. In the push-pull system III (e.g. tropolone), in spite of the great decrease of the basicity of the free lone pair by the intramolecular hydrogen bond (e.g. compared with tropone), Y remains the major site for intermolecular association. However in guaiacol, a non push-pull system III, the cooperativity effect makes the phenolic oxygen the major site.

A Program for Linear Regression with a Common Point of Intersection: The Isokinetic Relationship

A program is described for statistically correct calculations of the enthalpy-entropy relationship, applicable also generally for linear regression when several regression lines are constrained by a common point of intersection. Examples from the chemical literature show the difference between a correct and incorrect statistical treatment.

A Theoretical Evaluation of the pKHB and Δ

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.

H{{{\,\ominus}\hfill \atop {\rm HB}\hfill}}}

A set of 9,10-dihydro-9,10-ethano and ethenoanthracene derivatives was tested with the aim to quantify the effect observed on drug efflux. Structure activity relationships and molecular modeling studies allowed to define topological display of pharmacophoric groups for these reversal agents.