The mechanism of the remote polar substituents effect on formation of ion—molecular complexes

Journal of Molecular Structure, 88 (1982) 171-182 THEOCHEM Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands

THE MECHANISM OF THE REMOTE POLAR SUBSTITUENTS ON FORMATION OF ION-MOLECULAR COMPLEXES

EFFECT

L. A. GRIBOV, S. B. SAVVIN, M. M. REICHSTAT and M. Yu. ORLOV V.I. Vernadsky Institute of Geochemistry Sciences, Moscow, (U.S.S.R.)

and Analytical Chemistry, USSR Academy

of

(Received 13 July 1981)

ABSTRACT One of the important problems that theoretical chemistry poses is the mechanism by which polar substituents remote from the reaction centre affect the substitution and addition reactions and the bond energy of products. This influence is known to be considerable in protonation, complexing, and ion-molecular adducts formation and some other reactions. Moreover, this effect is widely used, e.g. to modify the properties of organic analytical reagents with the aim of increasing sensitivity, contrast range, and selectivity of analytical colour reactions [ 11. INTRODUCTION

Most standard textbooks share the opinion that the substituent effect is passed over the chain of bonds connecting a polar substituent and the reaction centre [2]. The introduction of a polar substituent, according to this viewpoint, leads to an alteration of the electron distribution even in a region several bond distances from the reaction centre. The analogy with the conducting system is obvious. Indeed, if an electric field is set up, or a point charge introduced in one part of the conducting system, redistribution of the charge in another part, though at a relative distance apart, will occur. To suit the theory, especially pronounced influences should be observed in molecules with clearly defined conjugation. Close examination, however, revealed that this concept is not always valid. Firstly, experimental evidence contradicts theory. Thus weak changes in force constants of the bonds remote from polar substituents, resonance methods data and others, clearly and unambiguously, indicate that introduction of polar substituents at distances several bond lengths from the reaction centre, even in the case of marked conjugation, does not cause significant electron redistribution. Secondly, special quantum mechanical calculations, partly reported in [ 31 as well as the data of other authors, confirm the experimental results. Thus, an introduction of a substituent in one of the azo-benzene rings [ 31 leads to 5% electron redistribution in the ring (as in the case of the benzene ring substitution); in passing to the second ring over OlSS-1280/82/0000-0000/$02.75

0 1982 Elsevier Scientific Publishing Company

172

the azo-bridge the electron substitution effect weakens tenfold. It is apparent that only in relatively small molecules (such as benzene), where a substituent is at most 2-3 bonds from the reaction centre the substituent electron effect passed over the chain of bonds may cause alterations in some chemical properties. Thirdly, in relatively small molecules even with conjugation an analogy cannot be drawn with the conducting systems, since this can be done when sufficiently broad partly filled energetic zones are present, which is not, and cannot be, the case with the medium-size molecules. All this forced us to suggest another mechanism of the remote polar substituents’ effect on the molecule’s reaction centre. We state that this effect is expressed in alteration of the electrostatic field of a reagent in the region of a reaction centre due to purely field effects [ 4-71. The reported findings demonstrate that the field changes markedly (sometimes by an order of magnitude or greater) and may also reverse the sign even at great distances from the polar substituent. The findings in refs. 6 and 7 establish correlations between the bond energy and electrostatic potential in complexes of alcohols with halide ions. The bond energy changes sharply when passing from ethanol to its chloromethyl derivative, whereas the charges at atoms, directly participating in the ion-molecular bond, change insignificantly as well as the nature of the charge transfer from the donor to acceptor. Previous authors have repeatedly dwelt (see, for example, ref. 8) on the electrostatic fields effect on the course of chemical reaction of organic molecules with the electrophilic agents. The nature of the potential surfaces of the chemical addition reactions, especially when charged particles or structures with great dipole moments are added, may be generally outlined as follows. At great distances, electrostatic interactions play the main role, and the surface of the electrostatic energy of the molecule interaction with a point charge or dipole should sufficiently closely follow the shape of the potential surface of reaction. At distances of the order of a bond length, a decisive part in interaction is played by the effects of the charge transfer. Of principal importance, however, is that the gradient of the potential surface at the initial stages of the reagent convergence (which is demonstrated by calculations of potential curves and surfaces of the ion-molecular and dipole-molecular type reactions) clearly correlates with the depths of the potential well, i.e. with the bond energies. The shape of the electrostatic hypersurfaces may also point to a probable site of attack. The shape of the electrostatic fields may serve to prognose, as indicated in refs. 9 and 10 and others, the course of protonation, formation of coordinate compounds and hydrogen-bonded associates, alkylation and others. Pyrazole and pyridine furnish an excellent example to investigate interaction of organic molecules with a proton and lithium cation. On introduction of substituents, we correlated changes in molecular characteristics (electron charge distribution and molecular electrostatic fields) with changes in the bond energies with the aforementioned cations. Also discussed in the

173

paper is the possible influence of the molecular external electrostatic field on the rate of chemical reactions. To illustrate, calculations of molecular electrostatic fields of substituted benzene are given. THE EFFECT OF A SUBSTITUENT BOND

ON THE STRENGTH

OF THE ION-MOLECULAR

As the particles converged, curves of the energy change and charge transfer were calculated by the CNDO/B method [ 111, and computations of molecular electrostatic potentials were performed based on the charge distribution at atoms (point approximation). The validity of this approximation will be discussed later. RESULTS

A pyrazole molecule establishes a considerable electrostatic field; the coordinate node of the molecule is surrounded by a field of negative sign (Fig. l(a)). Judging by the configuration of the external electrostatic field, the most advantageous cation approach to the molecule should follow the axis of the valency angle NIN2C. Figure l(b) shows the potential changes (in this direction) versus internuclear distances for a number of investigated substituted pyrazoles. As the distance from the pyrazole molecule increases, the potential drops to zero. When the substituent introduced makes a negative contribution to the field, the total potential curve of the substituted molecule lies below the pyrazole curve (for instance, the curve of 5-methyl-substituted derivative). Conversely, when the contribution is positive, the potential curve lies above the pyrazole curve. So, the field contribution of a substituent may be so significant that at some distance from the molecule the potential becomes positive (Cnitro and Cfluoro substituents). Curves of energy versus internuclear distances (cation-donating atom of ligand) were drawn for distances from 0.4 to 10 8, (Fig. 2). For molecules free from substituents establishing a positive field near donating atoms of ligands, the energy of interaction with the cation is always negative (for example, for pyrazole and 5-methyl pyrazole, Fig. 2). Whereas for molecules containing substituents with the positive field effect, the energy of interaction with the cation at great distances (in the order of 5-10 A) is positive and only for distances below 5 A, when charge transfer markedly increases, the energy becomes negative (6nitro and 4fluoropyrazole, Fig. 2). The maximum barrier for investigated substituents reaches several kilocalories per mole, the depth of minimum on the interaction curve also decreases. Charge alterations at the cation have the following shape (Fig. 2) : at internuclear distances above 6 A the charge transfer to the cation does not exceed 0.1%; 1% at 5 W, 5% at 4 II, and 15% at 3 A. When internuclear distances are within 3 A, charge transfer close to linearly depends on distance.

174

-0.01

-0.02

(0)

(b)

Fig. 1. (a) Map of molecular electrostatic potential of pyrazole (A--‘) and (b) distribution (along probable direction of interaction with cation) of external electrostatic field potential of substituted pyrazoles.

Correlating the charge transfer and energy changes curves we arrive at the following conclusion: at great distances (up to 4-5 A) interactions are purely electrostatic and they should not be attributed to charge transfer from ligand to cation; the cation effect on the organic molecule is displayed only in some polarization of the molecule. At distances below 4 A ; the charge is transferred intensively, and the system’s energy drops sharply. Figure 3(a) presents the curve of minimum depth (bond energy) versus potential of the field set up by the ligand near the equilibrium position (for lithium cation 2 A from the donating atom of nitrogen). As is evident from the figure, the minimum depth, i.e. the energy of the bond metalligand, linearly depends on the external electrostatic field potential. Analogously, the interaction of the substituted pyrazoles with a proton can be described: at great distances they interact electrostatically, which may with sufficient accuracy be considered as the interaction of a point charge and the field of the organic molecule; as the distance decreases (below 3-4 A) the charge transfer starts and the system’s energy falls. The energy of protonation linearly depends on the potential of the external molecular field (Fig. 4).

175

4X

/-

E(o.u.)

Calf; I 1 I I I I

I I I 1 ’ I I

j

i

q&i), l.0

e

0.8 a4

0

Fig. 2. Potential energy of interaction and charge transfer in systems: substituted pyrazoles(Pz)-lithium cation versus internuclear distance.

-0.16 94

-a14

’

-a12

-0.10

-0.03

-0.u2

-0.01

~ (e,fi

0

)

I D .

l

II

E (a.u.1 (b)

(a)

Fig. 3. (a) Energy of bond substituted pyrazoles+thium cation versus potential of ligand electrostatic field and (b) charge at nitrogen donor atom: l-5-CH,, 2-4-NH,, 3-Pz, 4-5-F, 5-5-CN, 6-4-CN, 7-5-Cl, 8-4-C& 9-4-F, lo-4-NO,, 11-5-NO,.

176

(a)

E (a.u.1

(b)

Fig. 4. (a) Affinity to proton in substituted pyrazoles versus electrostatic and (b) charge at nitrogen donor atom. For designations see Fig. 3.

field potential

We arrive at similar results while studying the interaction of the substituted pyridines with cations. The energy of the forming chemical bond also linearly depends on the potential of the substituted pyridine’s electrostatic field at the site of the cation attachment (Figs. 5 and 6). DISCUSSION

The introduction into the organic molecule of a substituent remotely spaced from the reaction centre leads to two main effects causing changes in the substance reactivity: changes in the electron distribution and changes in the external electrostatic field (changes in geometry may be neglected). As has been mentioned earlier [ 31, the effect of the remote substituent on the electron distribution at the reaction centre is negligible, the only result of substitution being the change in the external electrostatic field. In the circum-

w?

-0.16 -0.74

-0.12

-0.03

-0.m

-a02

-0.01

0

'dW8)

Y

-019.

?

15

l:9

P 3:

-0.20.

-024.

-0% E (a.u.1

; (b)

(a)

Fig. 5. (a) Energy of bond substituted pyridines(Py)-lithium cation versus electrostatic field potential and (b) charge at nitrogen donor atom: l-4-NH,, 2-4-CH,, 3-4-OH, 4-3-NH,, 5-4-CCH, 6-3.OH, 7-Py, 64-CH,F, 9-4-SH, lo-4-CCF, 11-3-SH, 12-4-F, 13-4-CN, 14-3-CN, 15-4-NO, 16-3-NO, 17-4-COH, 134-CHF,, 19-3C1, 20-4C1, 21-3-F, 22-3-COF, 23-4CF,, 24-3,4di-F, 25-3,5-d&F, 26-3,4-di-Cl, 27-3-NO,, 28-3,5-di-Cl, 29-4-NO,, 30-3,4,5-tri-F.

177

(b)

Fig. 6. (a) Affinity to proton in substituted and (b) charge at nitrogen donor atom.

(a) pyridines versus electrostatic

field potential

stances, this very change conditions the change in the chemical properties of the molecule-analogues. For comparatively small molecules of pyrazoles and pyridines, the introduction of substituents is accompanied by a change in the external field and also pronounced charge redistribution near the reaction centre. Let us now correlate the structural changes in the molecules with the changes in their reactivity. (1) The interaction with cations at great distances is purely electrostatic and may be described as the interaction of a charge with the external molecular field. In substitution, the energy changes in accordance with the changes in the external molecular field (Figs. 1 and 2). It should and has been noted earlier [ 41, that changes in the potential of the external electric field arise because of a non-uniform charge distribution at the substituent rather than charge redistribution at the atoms over the whole molecule. Generally speaking, changes in the external field potentials may occur contrary to the charge distribution at the reaction centres and contrary to its changes in substitution (compare electron and field effects of substituents, see Figs. 3-6, right and left). (2) The formation of a chemical bond ligand-cation is the result of a considerable redistribution of the electron density in the space between the reacting centres. This conclusion can be drawn from correlating the curves of charge transfer and energy change (Fig. 2). Obviously, this process will be governed by the total electron charge at the donor atom, at least by the total charge of the valency electrons participating in the bond. For the nitrogen atom in the aforementioned compounds, the value ranges from 5.10 to 5.20 e depending on the substituent electron effect. It is quite apparent that such a change cannot tell on the energy of the forming bond. (3) As Figs. 1 and 2 reveal, the substituent field affects the energy of a cation interaction with the molecule even at great distances. As the particles come closer together this contribution evidently increases, and at equilibrium the energies of cation interaction (chemical bond energies) with different

178

substituted, say, pyrazoles will differ by the energy of cation interaction with the substituent field. In the cases considered this contribution to the cation-ligand bond energy ranges from several to 15-20 kcal mol-’ for a substituent with strong field effects. (4) Quantitative comparison of the structural changes in substitution with changes in the chemical bond strength (Figs. 3-6) demonstrates that the latter correlates better with the changes in the external field potential than with those of the charge distribution at the reaction centre. Moreover, when a substituent gives the oppositely directed field and electron effects, the energy changes of the cation-molecule chemical bond occur in accordance with the field effect and opposite to the electron effect. It should be noted that the point approximation does not allow us to calculate adequately the potential at distances in the order of a chemical bond, but since the potential change is conditioned by a substituent 4-5 A away from the equilibrium cation position this change may be estimated even by such a rough approximation. The dependences depicted in Figs. 3-6 demonstrate that in case of substitution in the ligand the energy changes of the cation-ligand bond linearly depend on the substituent field effect. To prognose the effect of changes in the ligand structure on the strength of the metal complexes and ability to protonation, use is made of the presented or similar dependences of the minimum depth on the external field of the ligand. Comparison [12, 131 of the basicity of substituted pyridines in the gas phase and solutions demonstrates a linear dependence between the dissociation pK of protonated pyridines and the proton affinity. Hence, considering the relationship between the changes in the field and those in the protonation energy, one may hope that a linear dependence exists between the potential and protonation pK or dissociation pK of conjugated acids [ 14, 151 in substituted pyridines. The correlations given in Fig. 7 demonstrate a pK-potential dependence and far worse pK dependence on the charge changes at the protonated nitrogen atom. Theoretical organic chemistry uses the so-called Hammett constants to estimate the substituent effect on the reactivity of organic substances, in particular, on the acidity-basicity. These constants, taken from [ 161, adequately correlate with potential at the site of the proton attachment to the molecule of a substituted pyridine (Fig. 8) and the dependence on the charge in this case is also worse. Neglecting here the significance the Hammett constants have for estimating the reactivity of organic substances, we only want to note that these constants, as an experimental measure of the substituent effect on the properties of substances, take account of the substituent field effect. Thus, the field effect of remote polar substituents on the bond energy in the ion-molecular complexes may be clearly traced and used for corresponding prognoses. This influence considerably exceeds the effect of the electron distribution changes directly at the reaction centre. Therefore, the hypothesis as to the mechanism of the remote polar substituent’s effect on the

:

179

.

1 P'L

1

(b)

(a)

Fig. 7. (a) Dissociation pK of substituted pyridines conjugated field potential and (b) charge at nitrogen donor atom.

acids versus electrostatic

0.5

-a5 . 1

9.t=

’

-0.16

-c&l+ -a,_3

-4'10

-0.08

-0.M

-0.02

+ (e/8)

(a)

(b)

Fig. 8. (a) Substituents’ Hammett charge at nitrogen donor atom.

-3.06

constants versus electrostatic

field potential

and (b)

reactivity of molecules, suggested in [ 4-71, should be considered reliably proved. As noted above, this effect is expressed as the change in the electrostatic field in the region of the reaction due to the substituent field effect, rather than passed over the chain of bonds and manifested as charge redistribution at the reaction centre atoms. THE EFFECT OF A SUBSTITUENT

ON THE CHEMICAL REACTION

RATE

As stated above, the introduction of a substituent changes the external electrostatic field of an organic molecule and affects the interaction with charged particles at great distances and the bond energy of the forming ionmolecular complexes. Since the field can hinder or promote the particles’ convergence and also affect the chemical bond energy in the ion-molecular complexes (many of the so-called transition states should be classed with complexes of this type), then the introduction of substituents through

180

changes in the field should influence the absolute rates of chemical reactions. Since we are not attempting a quantitative treatment, we shall discuss the possible effect of the substituent field on the rate constant of some ion-molecular type reactions qualitatively. The rate constant, according to the Arrhenius equation, may be expressed as k = Ce-E/JW where constants C and E characterize the given reaction: E being the activation energy and C the frequency factor, the physical meaning of which is disclosed in the collision theory. In principle, the external electrostatic field affects both the exponent and the pre-exponential factor in the Arrhenius equation. Let us try to estimate this influence. Effect on the exponent The field of unsubstituted benzene 2-3 A from the periphery atoms is close to zero. The substituent introduction leads to the appearance of considerable external *fields (Fig. 9). To illustrate, for nitrobenzene (Fig. 9(a)), as our calculations show, the electrostatic field potential near the aromatic part of the molecule reaches 0.02 W-i, which corresponds to a single charge energy of 6 kcal mol-‘. Therefore, when a substrate molecule carries a polar substituent, the energy of a charged attacking particle (for instance, in electrophilic-substitution reactions) near the reaction centre changes by several kilocalories per mole. For two analogues, e.g. benzene and nitrobenzene, under the same reaction conditions and even in case of a competing reaction in the same reaction mixture, the energies of colliding particles (average energies) differ by the same several kilocalories per mole because of the substituent field effect only. Besides, the substituent field effect tells on the energy of the chemical bond in the transition complex; this has been shown above for protonation and complexing. Both the factors change the E/RT value and hence the rate of the analogues’ reactions. Effect on the pre-exponential factor As the earlier examples reveal, in substitution, the energy of the interacting particles at great distances (5-7 A) changes not only by several kilocalories per mole but may also reverse the sign. Under certain conditions such a field may promote or hinder the molecule convergence with an ion or dipole. For example, in the case of nitrobenzene nitration, where the nitronium-cation is the attacking particle, the nitro-group field effect hinders the particles’ convergence, which inevitably tells on the preexponential factor value (to use collision theory language this means the change in the effective diameter of collisions due to the long-range interactions).

181

(a)

0.001

kc!! 0.002

GH

-

HCC~cI

u

H 0

L/l

(b)

-0.002 -0.00’1

(cl

Fig. 9. Distribution of external electrostatic field potential (A-‘) for (a) nitrobenzene, (b) fluorobenzene and (c) aniline. The section is through the molecular plane.

Moreover, if the attacking particle bears a non-uniformly distributed charge, the substrate field definitely orients the particle; and this affects the successful outcome of collisions. Generally speaking, the external field through the action of two factors (change in the effective diameter of collisions and the reagent reorientation due to the long-range interactions) influences the effectiveness of collisions, which is reflected in the frequency factor change in the Arrhenius equation.

To illustrate, let us consider the field effects accompanying the substituent introduction into the benzene ring. We investigated benzene bearing the substituents -F, -OH, -SO,H, -NO,, -CF3, -CH3, -CN, -NH,, -CIAO, -COOH, differing by both the electron and the field effect. The substituents of the second class and halogens establish a positive field around the aromatic nucleus, while all the first class substituents minus the halogens set up a negative field. Thus, in the reactions of electrophilic substitution, the substituents setting up a positive field deactivate the nucleus, i.e. decrease the rate of corresponding reactions; and conversely, the substituents establishing a negative field activate the nucleus, i.e. increase the rate of electrophilic substitution reactions. It is apparent that the above-stated is not mere coincidence but may be explained by the field effect, first, on the effectiveness and energy of collisions and, second, on the chemical bond energy (in this case in the activated transition complex). Our reasoning touches only a theoretical model interaction of two particles - and disregards the effect of the medium. This problem is a rather complicated one and needs thorough investigation. The qualitative aspect of the problem is likely to remain unchanged; the reaction conditions, medium composition and reagent solvation may only increase or decrease the substituent field effects. REFERENCES 1 S. B. Sawin, Organic Reagents of Arsenazo III Group, Atomizdat, Moscow, 1968. 2 H. Becker, Einfiihrung in der Elektronentheorie organischchemischer Reaktionen, Berlin, VEB Deutscher Verlag der Wissenschaften, 1961. 3 M. M. Reichstat, S. B. Sawin and L. A. Gribov, J. Anal. Chem., 34,10 (1979) 1886 (in Russian). 4 L. A. Gribov, S. B. Savvin and M. M. Reichstat, J. Anal. Chem., 35, 8 (1980) 1469 (in Russian). 5 L. A. Gribov and S. B. Sawin, J. Mol. Struct., 71 (1981) 263. 6 L. A. Gribov, T. T. Merzlyak and I. S. Perelygin, J. Phys. Chem., 54,8 (1980) 2010 (in Russian). 7 L. A. Gribov, T. T. Merzlyak and I. S. Perelygin, J. Mol. Struct., 67 (1980) 1. 8 Yu. A. Panteleyev, Relationship between the electrostatic field of a molecule and its reactivity. Quantum-chemical Consideration, Preprint of V. G. Khlopin Radium Institute, Leningrad, 1977 (in Russian). 9 R. Bonaccorsi, C. Petronglo, E. Scrocco and J. Tomasi, Theor. Chim. Acta, 20 (1971) 331. 10 R. Bonaccorsi, A. Pullman, E. Scrocco and J. Tomasi, Theor. Chim. Acta, 24 (1972) 51. 11 J. A. Pople and G. A. Segal, J. Chem. Phys., 43 (1965) 136. 12 D. H. Aue, H. M. Webb, M. T. Bowers, Ch. L. Liotta, C. J. Alexander and H. P. Hopkins, J. Am. Chem. Sot., 98 (1976) 853. 13 M. Taagepera, W. G. Henderson, R. T. S. Brownlee, J. L. Beauchamp, D. Holtz and R. W. Taft, J. Am. Chem. Sot., 94,4 (1972) 1369. 14 A. Fischer, W. J. Galloway and J. Vaughan, J. Chem. Sot., 10 (1964) 3591. 15 A. Bryson, J. Am. Chem. Sot., 82,18 (1960) 4871. 16 A. Gordon and R. Ford, The Chemist’s Companion, Wiley-Interscience, New York and London, 1972.