Zeroual & al. / Mor. J. Chem.

3 N4 (2015) 698-704

The regio- and stereoselective addition

dichlorocarbene onto -himachalene

of

dibromocarbene

and

A. Zeroual 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 16 May2015, Revised 24 May 2015, Accepted 02 Oct 2015

Abstract
In this work we used DFT B3LYP/6-31G (d) to study the mechanism, the regio- and stereoselectivity of the
[1+2] cycloaddition reaction between -himachalene and dihalogenocarbene. Analysis of the reactivity
indices and calculation of the activation energies of the transition states showed that this reaction is
stereoselectives, the treatment of -himachalene with one equivalent of dibromocarbene leads via an
exothermic reaction to the formation of a single product P1 resulting from the attack of the most substituted
double bond C6=C7 of -himachalene. Treatment of product P1 with one equivalent of dichlorocarbene
leads, again via an exothermic reaction, to formation of the two products P3 and P4, but dibromocarbene
does not react with the product P1 due to the high activation energy of this reaction.
Key words: Nucleophilicity; electrophilicity; [1+2] cycloaddition; stereoselectivity; regioselectivity, DFT.

I. Introduction
The classic route to prepare cyclopropanes is a cycloaddition [2+1], concerted and stereospecific, between
an olefin and a carbene. Deprotonation of chloroform or bromoform with a strong base (for example tBuOK) in organic medium, or with sodium hydroxide in catalysis by phase transfer, is an excellent method
for synthesizing cyclopropane compounds [1]. It method was therefore implemented to prepare all
cyclopropanes used in this study. In the first reaction the - himachalne reacted with one equivalent of
dibromocarbene, chemo-specifically results in a single compound P1 resulting from the attack of the double
bond C6= C7 with the side (Figure 1), the structure was determined by spectral data (NMR, 1H, 13C) [2],
and the stereochemistry was confirmed by X-ray diffraction [3]. Thus, the action at a temperature of 0 C,
with a stoichiometric amount of dichlorocarbene (generated in situ under the conditions of the transfer
catalysis solid-liquid phase (CTP-LS) from chloroform and sodium hydroxide) in presence of
benzyltriethylammonium chloride (TEBA-Cl) as a catalyst on the product P1 leads at the end of two hours to
the products P3 and P4. The structures of the products P3 and P4 were determined by spectral data (NMR, 1H,

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13

C) and the stereochemistry was confirmed by X-ray diffraction [4]. For the same conditions against solidliquid phase transfer P1 product does not react with dibromocarbene (reaction 3). (Figure 1).
Br

Br

Br

Br
CHBr3 / NaOH

TBEA-Cl / CTP-LS

Reaction 1

P2 0%

P1 100%

B-Himachalene

Br

Br
Br

Br
CHCl3 / NaOH

Br

TBEA-Cl / CTP-LS
Reaction 2

Cl

Br

Cl

Cl

P3 85%

H
Cl
P4 15%

Br

Br

Br

P1

Br

CHBr3 / NaOH

TBEA-Cl / CTP-LS
Reaction 3

Br
Br

P5

Br

H
Br
P6

Figure 1: Cycloaddition of dihalogenocarbene and -himachlene

In this work we study these reactions by the method of density functional theory (DFT) B3LYP/6-31(d) and
compare them with experimental results.
DFT (density functional theory) computations were carried out using the B3LYP [5-6] exchange-correlation
functionals, together with the standard 6-31G(d) basis set.[7] The optimizations were carried out using the
Berny analytical gradient optimization method.[8-9] The stationary points were characterized by frequency
computations in order to verify that TSs have one and only one imaginary frequency. The IRC paths [10]
were traced in order to check the energy profiles connecting each TS (transition state energy) to the two
associated minima. All computations were carried out with the Gaussian 09 suite of programs. [11].

The global electrophilicity index, [12] , is given by the following expression, = , in terms of the
electronic chemical potential and the chemical hardness . Both quantities may be approached in terms of
the one-electron energies of the frontier molecular orbital HOMO and LUMO, as and ,

+
= 2
and = , respectively.[13-14] Th nucleophilicity index[15-16] N,
based on the HOMO energies obtained within the KohnSham scheme,[17] and defined as =
( ). The nucleophilicity is referred to tetracyanoethylene (TCE). The +
electrophilic and nucleophilic Parr functions, [18-28] which allow for the characterisation of the
electrophilic and nucleophilic centers of a molecule, were obtained through the analysis of the Mulliken
atomic spin density of the radical anion and the radical cation of the studied molecules, respectively.

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II.Results and Discussion

II.1. The intramolecular chemical descriptors of the -himachalne and the dibromocarbene.
Electronic chemical potential (), the index of the electrophilicity () and the nucleophilicity index (N)
calculated for -himachalne and dibromocarbene are shown in table 1.
Table 1: Electronic chemical potential (), global electrophilicity (), and global nucleophilicity (N), in eV.

N
-himachalene
-2.499 0.489 3.427
Dibromocarbene -5.332 4.107 2.469
The electronic chemical potential of -himachalne (-2.499 eV) is higher than dibromocarbene (-5.332
ev), which means that the electron transfer takes place of -himachalne to dibromocarbene.
The global electrophilicity of the dibromocarbene (4.107eV) is greater than that of -himachalne (0.489
eV). Therefore, in this cycloaddition the dibromocarbene will behave as electrophilic while the himachalne will behave as nucleophilic, we can conclude the same thing from the nucleophilicity values.
II.2. Comparative analysis of local indexes for the reactants in the first reaction.
The local electrophilicity values k for carbene and local nucleophilicity Nk for C2 atoms, C3, C6 and C7
of the -himachalene calculated with the function Parr (atomic spin density) are reported in table 2.
Table 2: Electrophilic and nucleophilic Parr functions,
nucleophilicity.
Reactifs
N carbone P +
Dibromocarbene CBr2
0.979
C2
0.08
-himachalene
C3
0.13
C6
0.27
C7
0.28

and the local electrophilicity and local

P0.706
0.14
0.09
0.25
0,27

k
4.020
0.05
0.09
0.18
0.19

Nk
1.743
0.47
0.30
0.85
0.92

These results show that the most favored interaction takes place between the carbene carbon atom (with the
highest value of k) and atoms C6 and C7 -himachalne (with the highest value of Nk). Therefore, the
regioselectivity observed experimentally is correctly predicted by Parr functions.
At the end highlight that the attack of the double bond C6 = C7 -himachalene is preferred, we are studying
stereo-selectivity of binding C6 = C7.
II.3. Study of stereoselectivity of the double bond C6 = C7.
It was found the attack of the double bond C6=C7 by the side of -himachalene is preferred. We
determined the energies of reactants, the energies of the products, the energies of TS, TS and deference of
transition energy (Table 3).

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Table 3: Total (E, in au) and relative (E, in kcal /mol) energies of the stationary points involved in the
cycloaddition [1+2] between -himachalene and dibromocarbene.
E (u.a)
E*(kcal/mol) (E ER)
(TSTS) Kcal/mol
Reactifs
(-himachalene +CBr2)
-5767.430
--------ETS 1
-5767.424
3.765
8.157
ETS 2
-5767.411
11.922
Product P1
-5767.534
-65.262
Product P2
-5767.509
-49.573
The difference between the activation energies of products P1 and P2 is 8.16 kcal/mol indicating that the
formation of the alpha isomer is kinetically favored over the beta isomer. The calculation is in agreement
with the experimental results.
II.4. Theoretical studies of the stereoselectivity of the cycloaddition reaction [1+2] between the P1 and the
dihalogenocarbene.
Table 4: The chemical descriptors intramolecular (in eV) for
dibromocarbene.

Product P1
-3.44 1.06
Dichlorocarbene -5.45 3.90
Dibromocarbene -5.33 4.10

the product P1, dichlorocarbene and

N
3.3
2.17
2.46

Table 5: Total (E, a.u) and Relative (E, kcal/mol) Energies of the Stationary Points Involved in the
Addition Reaction to the product P1 and dihalogenocarbene.
E (u.a)
E*(Kcal/mol) (TSTS) (Kcal/mol)
(E ER)
(P1+CCl2) -6725.917 --------ETS 3
-6725.892 15.687
16.315
ETS 4
-6725.866 32.002
Product 3 -6725.997 -50.200
Product 4 -6725.999 -51.455
(P1+CBr2) -10948.934 --------ETS 5
-10948.903 19.452
17.570
ETS 6
-10948.875 37.023
Product 5
Product 6

-10949.021 -54.593
-10949.025 -57.103

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* The electrophilicity index of dibromocarbene and dichlorocarbene (4.10 eV and 3.90 eV), respectively, are
higher than that of the product P1 (1.06 eV). Therefore, in this cycloaddition the dihalogenocarbene behaves
as an electrophile while the product P1 will behaves as nucleophile. (Table 4)
* The chemical potential of the product P1 (-3.44 eV) is higher than dihalogenocarbenes (-5.33 eV, -5.45
eV), which implies that the electron transfer takes place from the product P1 to dihalogenocarbenes.
Experimentally the attack of the double bond C2 = C3 by the side of the product P1: ((1S, 3R, 8S) -2,2dibromo-3,7,7,10- tetramethyltricyclo [6.4.0.01,3] Dodec -9-ene is preferred, we determined the energies of
reactants, the energies of the products, the transition energy TS, the transition TS and deference of the
transition energy (table 5).
Table 6 :activations energies of alpha and bita faces for reactions 2 and 3
E*(kcal/mol)
[E*(kcal/mol]
ETS 3 (dichlorocarbene)
15.687
3.765
ETS 5 (dibromocarbene)
19.452
ETS 4 (dichlorocarbene)
32.002
5.021
ETS 6 (dibromocarbene)
37.023

= .

= .

= .

= = . + . + ( )
Dibromocarbene

Dichlorocarbene

R(C) = 70 pm
R(Br)=115 pm
d1=191.82 pm
1 (Br-C-Br)= 109.427
D1=561.82 pm
h1=324.507 pm
r1=458.557 pm
V1=0.071 (nm)3

R(C) = 70 pm
R(Cl)=100pm
d2=175.26 pm
2 (Cl-C-Cl)= 109.317
D2=515.26 pm
h2=298.026
r2=420.297
V2=0.055 (nm)3

Table 5 shows that:

The formation of products P3, P4, P5 and P6 are exothermic by -50.200, -51.455, -54.593 and -57.103
kcal/mol respectively and thermodynamically favorable.
The transition state energy of the side of double bond C2=C3 is located in front 16.315 and 17.570
kcal/mol below the transition state energy of the side for reaction 3 and reaction 4 respectively.
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The difference between the activation energies of products P3 and P4 is of order 16.315 kcal/ mol,
indicating that the formation of alpha stereoisomer are kinetically favored over the beta stereoisomer. The
result is in agreement with the experimental results.
Under the same experimental conditions P1 does not react with dibromocarbene. To find out why this so, we
compare the energy of activation recent reactions (reactions 2 and 3) and the size of dihalogenocarbene used
we gather in Table 6 activations energies of alpha and bita faces for reactions 2 and 3, we also collect in this
table geometrical parameters of dihalogenocarbene.
The bromine atom is larger than the chlorine atom which makes the lengths and bond angles in the dibromocarbene (d1=191.82 pm, 1 (Br-C-Br)= 109.4276) greater than in the dichlorocarbene (d2=175.26 pm, 2
(Cl-C-Cl)= 109.3176) and the free rotation of the molecules in the solvent, it will consider that the carbenes
(singlet carbene) have shapes of cones. We gather in Table 6 relations used to calculate the parameters of the
cones. We find that the volume of dibromo-carbene (0.071 nm3) is greater than the volume of
dichlorocarbene (0.055 nm3), so the steric hindrance created by the methyl carried by the C11 carbon is most
important with the dibromo-carbene than dichlorocarbene which make the activation energies of the third
reaction greater than those of the second reaction. So the reaction 3 is difficult to achieve experimentally,
then it is necessary to estimate the other terms (solvent, temperature, catalyst ...).

IV. Conclusion
The regio- and stereoselectivity of the reaction between -himachalene and dibromocarbene was studied
using DFT B3LYP/6-31G (d). Analysis of the global electrophilicity and nucleophilicity indices showed that
-himachalene P1 behaves as a nucleophile, while dibromocarbene and dichlorocarbene behaves as an
electrophile. The regioselectivity found experimentally was confirmed by local indices of electrophilicity
and nucleophilicity k and Nk. Calculation of activation energies shows that this reaction stereoselective
reaction takes place at the side of the double bond C6=C7 of -himachalene. Treatment of product P1 with
one equivalent of dichlorocarbene leads to formation of the two products P3 and P4 we showed that the
reaction is stereoselective too, but dibromocarbene does not react with the product P1 because the activation
energies of this reaction ( and sides) are very high.

Reference
[1]M. Fedoryski, Chem. Rev., 103 (2003) 1099-1132.
[2]H. Eljamili, A. Auhmani, M. Dakir, E. Lassaba, A. Benharref, M. Pierrot, A. Chiaroni, and C. Riche,
Tetrahedron Letters, 43 (2002) 6645-6648.
[3]A. Benharref, L. El Ammari, E. Lassaba, N. Ourhriss, M. Berraho, Acta Cryst., E68 (2012) o2502.
[4]N. Ourhriss, A. Benharref, M. Saadi, M. Berraho, L. El Ammari, L. Acta Cryst. E69 (2013) o724.
[5]C. Lee, W. Yang, R. G. Parr, Phys. Rev. B., 37 (1988) 785-789.
[6]A. D. Becke, J. Chem. Phys. 98 (1993) 5648-5652.
[7] W. J. Hehre, L. Radom, P. V. R. Schleyer, J. A. Pople, New York, 1986.
[8] H. B Schlegel, J. Comput. Chem. 2 (1982) 214-218.
[9]H. B. Schlegel, ed. D.R. Yarkony, World Scientific Publishing, Singapore, 1994.
[10]
K. Fukui, J. Phys. Chem. 74 (1970) 4161-4163.
[11] M. J. Frisch, and al., Gaussian 09, Revision A.02, Gaussian, Inc., Wallingford CT, 2009.
[12] R. G. Parr, L. V. Szentpaly, S. Liu, J. Am. Chem. Soc.., 121 (1999) 1922-1924.
703

Zeroual & al. / Mor. J. Chem. 3 N4 (2015) 698-704

[13] R. G. Parr, R. G. Pearson, J. Am. Chem. Soc., 105 (1983) 7512-7516.

[14] R. G. Parr, W. Yang, Oxford University Press, New York, 1989.
[15] L. R. Domingo, E. Chamorro, P. Prez, J. Org. Chem., 73 (2008) 4615-4624.
[16] L. R. Domingo, P. Prez, Org. Biomol. Chem., 9 (2011) 7168-7175.
[17] W. Kohn, L. Sham, J. Phys. Rev., 140 (1965) 1133-1138.
[18] L. R. Domingo, P. Prez, J. A. Sez, RSC Advances, 3 (2013) 1486-1494.
[19] L. R. Domingo,J. A. Sez, J. A. Joule, L. Rhyman, P. Ramasami, The Journal of Organic Chemistry,
78 (2013) 1621-1629.
[20]
L. R. Domingo, J. A. Sez, M. Arn, Organic & Biomolecular Chemistry. 12 (2014) 895-904.
[21] A. Monlen, G. Blay, L. R. Domingo, M. C. Moz, J. P. Pedro, J. Chem. Eur, 19 (2013) 1485214860.
[22] L. R. Domingo, J. Maria, M. J. Aurell, P. Prez, RSC Advances, 4 (2014) 16567.
[23] L. R. Domingo, M. J. Aurell, J. A. Sez, S. M. Mekelleche, RSC Advances, 4 (2014) 25268-25277.
[24] L. R. Domingo, RSC Adv, 4 (2014) 32415-32428.
[25]
A. Zeroual. A. Benharref, A. El Hajbi, J Mol Model., 21 (3) (2015) 2594-2599.
[26] M. Esseffar, R. Jalal, M. J. Aurell, L. R. Domingo, Computational and Theoretical Chemistry, 2014,
1030, 25
[27] A. Zeroual, M. Zoubir,R. Hammal, A. Benharref, A. El Hajbi, Mor. J. Chem., 3 (2) (2015) 356-360
[28] . A. Zeroual, R. Hammal, A. Benharref, A. El Hajbi, Journal of Computational Methods in
Molecular Design, 4 (3) (2014) 106-112.

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