Zeroual & al. / Mor. J. Chem.

3 N2 (2015) 356-360

Understanding the regioselectivity and reactivity of FriedelCrafts

benzoylation using Parr functions
A. Zeroual a*, M. Zoubir a, R. Hammal a, A. Benharref b and A. El Hajbi a
a

Laboratory of Physical Chemistry, Department of Chemistry, Faculty of Science Chouaib Doukkali

University, El Jadida, Morocco
b
Laboratory of Biomolecular Chemistry, Natural Substances and Reactivity, URAC 16 Semlalia Faculty of
Sciences, Cadi Ayyad University, Marrakech, Morocco

Corresponding author. E-mail address: zeroual19@yahoo.fr

Received 04 Fev 2015, Revised 17 Feb 2015, Accepted 05 Mars 2015

Abstract
A theoretical study of the reactivity and regioselectivity of some aromatic compounds in electrophilic
aromatic substitution was carried out using density functional theory with B3LYP/6-31G(d). The relative
reactivity of these systems was rationalized by means of the global nucleophilicity index. Positional
selectivity, namely o, m or p, is predicted by means of the local nucleophilicity indices (Parr functions).The
present study shows that the experimental results of the relative reactivity and regioselectivity of these
reactions are correctly predicted using Parr functions.
Key words: aromatic substitution, DFT, electrophilicity, nucleophilicity, regioselectivity, Parr functions

Introduction
The Friedel-Crafts benzoylation of aromatics is the main route for the formation of aromatic ketones in
organic synthesis. These aromatic ketones are widely used in the production of pharmaceuticals, fragrances,
flavours, insecticides and other products [1]. Generally, these reactions are catalyzed by homogenous Lewis
acids such as AlCl3, BF3, FeCl3, ZnCl2 or strong protonic acids (H2SO4, HF) [2]. However, these traditional
catalysts have limitations such as environmental pollution hazards arising from the disposal of potential
toxic wastes, reactor corrosion, and difficulties in their handling [3, 4]. To avoid these problems, in recent
years, zeolites have come to be used increasingly as an environmentally friendly solid acid catalyst for
FriedelCrafts benzoylation of aromatic hydrocarbons [5], or else the reactions are carried out under
solvent-free conditions, with dramatic reduction of reaction time compared to standard methods (Figure 1)
[7].

R1

R2

Cl

R1

MW, solvent-free

R2

Figure 1. Benzoylation of various aromatic compounds (MW: microwave)

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Our aim in this work is to present a theoretical study on the reactions of electrophilic aromatic substitutions.
We chose aromatic molecules as substitutes (Figure 2) and compared the results of our calculations with
experimental results available in the literature [20].
OCH3

CH3

CH3

ispr

OCH3
OCH3

H3C

H3CO

3
2

SMe

Et

1
2

6 CH3

OCH3

Figure 2. Aromatic molecules used as substitutes

Computational methods
Density functional theory (DFT) [7, 8] computations were carried out using B3LYP [9] exchangecorrelation functionals with the standard 6-31G(d) basis set [10]. Optimization was carried out using the
Berny analytical gradient optimization method [11]. All computations were carried out with the Gaussian 09
suite of programs [12]. The global electrophilicity index [13] is given by the expression =2/2. where
is electronic chemical potential and is chemical hardness. Both quantities may be considered in terms of
the one-electron energies of the HOMO and LUMO frontier molecular orbitals, as HOMO and LUMO,
=(HOMO+ LUMO)/2 and =(HOMO - HOMO) respectively [14]. We introduced an empirical (relative)
nucleophilicity index N [15], based on the HOMO energies obtained within the KohnSham scheme [16]
and defined as N= (EHOMO(Nu) EHOMO(TCE)).
Nucleophilicity is calculated with reference to tetracyanoethylene (TCE), because this compound presents
the lowest HOMO energy of a large series of molecules already investigated in the context of polar
cycloadditions, which allows us to handle a nucleophilicity scale of positive values easily. The Pk+
electrophilic and Pk- nucleophilic Parr functions [17] which enable characterization of the electrophilic and
nucleophilic centers of a molecule were obtained by analysis of the Mulliken atomic spin density of the
radical anion and the radical cation respectively of the molecules studied.

Results and discussion

Prediction of relative reactivity
The global indices obtained using DFT are a powerful tool for understanding the behavior of polar reactions.
The difference in global electrophilicity between two reactants [18] can be used to predict the polar
character of the process and thus the feasibility of the cycloaddition. Table 1 shows the static global
properties: electronic chemical potential , global electrophilicity , nucleophilicity N and difference of
global electrophilicity . (Table 1)

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Table 1. Global reactivity indices , , and N for compounds 1-8 and benzoyl chloride (Figure 2) calculated
using DFT/B3LYP/6-31G(d)
(ev)
(ev)
N (ev)
(ev)
Compound
-3.216
0.802
2.92
1.32
1
-3.127
0.749
2.97
1.37
2
-3.138
0.752
2.947
1.37
3
-3.277
0.953
3.268
1.17
4
-3.037
0.719
3.118
1.40
5
-2.985
0.703
3.208
1.42
6
-2.859
0.709
3.621
1.41
7
-2.653
0.592
3.739
1.53
8
-4.785
2.124
1.877
-----Benzoyl chloride
The electronic chemical potential of eight aromatic compounds (-3.216, -3.127, -3.138, -3.277, -3.037, 2.985, -2.859, -2.653 eV) is greater than that of benzoyl chloride (-4.785), which implies that the transfer of
electrons takes place from the aromatic compounds to benzoyl chloride.
The electrophilicity index of benzoyl chloride (2.124 eV) is greater than that of all eight aromatic
compounds (column 3). Consequently in this electrophilic aromatic substitution benzoyl chloride behaves as
an electrophile while the eight aromatic compounds behave as nucleophiles.
The global nucleophilic indices of the reactants confirm that benzoyl chloride is an electrophile and that
the eight aromatic compounds are nucleophiles.
Using local nucleophilicity indices to predict the regioselectivity of electrophilic aromatic substitution
reactions
According to the polar model proposed by Chattaraj [19], the local philicity indices k and Nk are reliable
indicators for predicting the most favored interaction between two polar centers. The most favored
regioisomer is that which is associated with the highest local electrophilicity index k of the electrophile and
the highest local nucleophilicity index Nk of the nucleophile. We determined Nk for aromatic compounds 1-8
in order to predict the most likely electrophile/nucleophile interaction throughout the reaction pathway, in
order to elucidate the regioselectivity of these reactions.
Table 2 summarizes the values of nucleophilic Parr functions and local nucleophilicity for the eight aromatic
compounds and benzoyl chloride.
The results show that the most favored interaction will take place between the para center of aromatic
compounds (possessing the highest value of Nk). The values of Nk for atoms 4 and 6 of compounds 5 and 8
allow us to characterize the most favorable interaction. For the atoms in the ortho and meta positions in
compounds 6 and 7 we see that the local nucleophilicity is condensed, indicating that these atoms are those
involved in the most favorable interaction. Consequently, experimental regioselectivity is correctly predicted
by Parr function [20].

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Table 2. Nucleophilic Parr functions Pk- and local nucleophilicity values Nk at the o, m and p positions of
aromatic compounds 18. The greatest values of local nucleophilicity indices are given in bold.
Compound
PkNk
Experimental Yield (%)
o
0.075
0.219
5
1
m
-0.02
-0.058
0
p
0.43
1.255
90
o
0.07
0.207
26
2
m
-0.01
-0.029
3
p
0.46
1.366
71
o
0.082
0.241
23
3
m
-0.02
-0.058
7
p
0.44
1.296
70
o
0.138
0.450
10
4
m
-0.071
-0.232
0
p
0.309
1.009
90
2
-0.098
-0.305
0
5
5
-0.15
-0.467
0
4=6
0.4
1.247
100
6
o
0.42
1.347
79
m
0.01
0.032
21
o
-0.07
-0.253
0
7
m
0.18
0.651
100
2
-0.044
-0.164
0
8
5
-0.169
-0.631
0
4=6
0.43
1.60
100

Conclusion
In this work, we have theoretically examined the reaction of a series of aromatic compounds with benzoyl
chloride in electrophilic aromatic substitution. Our calculations show that experimental regioselectivity is
correctly reproduced. The local nucleophilicity index predicts that the some C position is more reactive than
other one in all systems. Our calculations also show that the Parr function correctly reproduces the relative
reactivity of the carbone position in these compounds: the interaction takes place between the carbone of
benzoyl and para position of compounds 1-4 and position 6 of the compounds 5 and 8. We conclude that
local nucleophilicity, as defined by Domingos group using the nucleophilic Parr function, reliably predicts
regioselectivity in electrophilic aromatic substitution.
References
[1]P. Geneste, A. Finiels, Catalysts for Fine Chemical Synthesis Microporous and Mesoporous Solid
Catalysts; Derouane, E.G., Ed.; John Wiley & Sons Ltd, Chichester, 2006, 95-104.
[2]G.A. Olah, Friedel-Crafts and Related Reactions, vol. 1, Wiley Interscience, New York, 1963.
[3]M. Yadav, U. Sharma, J. Mater. Environ. Sci. (2011) 407-414.
359

Zeroual & al. / Mor. J. Chem. 3 N2 (2015) 356-360

[4]A. El-Abbassi, H. Kiai, J. Hoinkis, A. Hafidi, J. Mater. Environ. Sci. (2014) 57-66.
[5]T. Raja, A. P. Singh, A. V. Ramaswamy, A. Finiels, P. Moreau, Applied Catalysis A: General. 211
(2001) 31-39.
[6]A. Rudolph, N. Rackelmann, M. O. Turcotte-Savard, M. Lautens, J. Org. Chem. 74 (2009) 289-297.
[7] N. Bouzayen, M. Mbarek and K. Alimi, Mor. J. Chem. (2015) 28-39.
[8]A. Benallou, H. Garmes, H. El Alaoui El Abdallaoui, Mor. J. Chem. (2014) 181-193.
[9]A. D. Becke, J. Chem. Phys. 98 (1993) 5648-5653.
[10] W. J. Hehre, L. Radom, P. V. R. Schleyer, J. A. Pople, Ab Initio Molecular Orbital Theory, Wiley, New
York, 1986.
[11] H. B. Schlegel, J. Comput. Chem, 3 (1982) 214-218.
[12] M. J. Frisch et al. Gaussian 09, Revision A.02, Gaussian Inc., Wallingford CT, 2009.
[13] R. G. Parr, L. V. Szentpaly, S. Liu, J. Am. Chem. Soc., 121 (1999) 1922-1924.
[14] R. G. Parr, R. G. Pearson, J. Am. Chem. Soc., 105 (1983) 7512-7516.
[15] L. R. Domingo, P. Prez, Org. Biomol. Chem, 9 (2011) 7168 7175.
[16] W. Kohn, L. J. Sham, Phys. Rev., 140 (1965) 1133-1138.
[17] A. Zeroual, A. Benharref, A. El Hajbi, J Mol Model, 21 (3) (2015) 2594-2599.
[18] L. R. Domingo, M. J. Aurell, P. Prez, R. Contreras, Tetrahedron, 58 (2002) 4417-4423.
[19] P. K. Chattaraj, U. Sarkar, DR. Roy, Chem. Reviews, 106 (2006) 2065-2091.
[20] P. Hoang, T. Ngoc, B. L. Do, T. Le Ngoc, Tetrahedron Letters, 55 (2014) 205-208.

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