International Journal of Chemical Modeling ISSN: 1941-3955 Volume 4, Number 1 © 2012 Nova Science Publishers, Inc.

THEORETICAL STUDY OF NUCLEOPHILIC

BEHAVIOUR OF 3,4-DIOXA-7-THIA-CYCLOPENTA[A]PENTALENE AND 3,7-DIOXA-4-

THIA-CYCLOPENTA[A]PENTALENE USING AB INTIO

AND DFT BASED REACTIVITY DESCRIPTORS

Banjo Semire and Olusegun Ayobami Odunola Department of Pure and Applied Chemistry, Ladoke Akintola University of Technology,

Ogbomoso, Nigeria

ABSTRACT

Calculations of HF/6-31G* and DFT-B3LYP/6-31G* based reactivity descriptors are reported for Furan (1), thiophene (2), thieno[3,2-b]furan (3) and the isomeric 3,4-Dioxa-7-thia-cyclopenta[a]pentalene (4) and 3,7-Dioxa-4-thia-cyclopenta[a]pentalene (5) in order to get insight into the factors determining the nature of their interactions with electrophiles. Global reactivity descriptors such as ionization energy, molecular hardness, electrophilicity, frontier molecular orbital energies and shapes, total energies were determined and used to identify the differences in the stability and reactivity of 3,4-Dioxa-7-thia-cyclopenta[a]pentalene and 3,7-Dioxa-4-thia-cyclopenta[a]pentalene. Additionally, Mulliken charge, local ionization energy and electrostatic potential energy surfaces revealed structural differences of isomeric these heterocycles. Calculated values led to the conclusion that heterocyclic 3,4-Dioxa-7-thia-cyclopenta[a]pentalene was more aromatic and stable than its isomeric 3,7-Dioxa-4-thia-cyclopenta[a]pentalene. Theoretical results showed exceptional reactivity of C(2),C(2*) atom for 4 and C(1*) atom for 5.

INTRODUCTION

Diels-Alder reaction (D-A) is one of the most widely used synthetic strategies for the synthesis of natural products due to its character of generating cyclic systems. By this reaction cyclic compounds characteristic of some families of alkaloids may be directly developed and synthesized (Biolatto et al, 1999 and Della Rosa et al, 2004). The use of

Corresponding e-mail: semireban@yahoo.com

Banjo Semire and Olusegun Ayobami Odunola 88

aromatic compounds as dienes has been widely studied in D-A reactions, however, the use of

them as dienophiles is a new and interesting branch that allows to state large and versatile

synthetic sequences.

Moreover, nowadays, computational chemistry methods offer a unique ability for organic

chemists to generate optimal geometry structures, the structural and electronic properties of

reactants and products make decisions as to which of the chemical transformations will occur

in reactions.

From the theoretical point, the differences in the stability of heterocycles are explained in

terms of aromaticity and delocalization of electron densities on π molecular orbitals. For the

stable compounds, a high π molecular orbital delocalization established between two aromatic

rings, which may not be presented in the less stable isomers.

It is evident that the aromaticity correlates with the thermodynamic stability of a system,

and also there is relationship between hardness and stability. Parr and Pearson (Zhou and

Navangul, 1990; Chamizo et al, 1993; and Bird, 1997) reported the principle of maximum

hardness (absolute hardness) η. For an N-electron system with total energy E and η are

defined as;

)(2

1)(

)(2

2

AIN

Erv

(1)

In the formula I is the vertical ionization energy and A stands for the vertical electron

affinity. According to the Koopmans theorem (1933), the hardness corresponds to the gap

between the HOMO and LUMO orbitals:

LUMOHOMOEAEI ,

(2)

Hence, the principle of maximum hardness confirms the results that show that stability of

aromatic hydrocarbons depends on HOMO-LUMO energy gap. The larger the HOMO-

LUMO energy gap the harder molecule. The higher HOMO energy corresponds to the more

reactive molecule in the reactions with electrophiles.

The electron affinity can also be used in combination with ionization energy to

give electronic chemical potential μ defined by Parr and Pearson (Pearson, 1993) as the

characteristic of electronegativity of molecules:

)(2

1

2

1)(

)( LUMOHOMOrvEEAI

N

E

(3)

The global electrophility index ω was introduced by Parr et al (1999) and calculated

using the electronic chemical potential μ and chemical hardness η.

2

2

(4)

Theoretical Study of Nucleophilic Behaviour ... 89

According to the definition this index measures the propensity of a species to accept

electrons. As Domingo et al (2002) proposes the high nucleophility and electrophility of

heterocycles corresponds to opposite extremes of the scale of global reactivity indexes. A

good, more reactive, nucleophile is characterized by a lower value of μ, ω and in opposite a

good electrophile is characterized by a high value of μ, ω.

The use of molecular surfaces, based on the molecular electron density such as the

molecular electrostatic potential (MEP) (Politzer and Truhlar, 19981; Ehresmann, 2003) has a

long tradition in the qualitative interpretation of chemical reactivity. The molecular

electrostatic potential gives a powerful description of molecular properties, such as strong

non-covalent interactions, that are predominantly electrostatic in nature. However, much

classical chemical reactivity depends on electron donor–acceptor interactions that are not

encoded in the MEP. The absolute reactivity can be judged from the values of the local

ionization energy at the π-surface of the aromatic compound.

Here we would study the electrophilic substitution reactions with Furan (1), Thiophene

(2), Theno[3,2-b]furan (3), 3,4-Dioxa-7-thia-cyclopenta[a]pentalene (4) and 3,7-Dioxa-4-thia-

cyclopenta[a]pentalene (5) using computational chemistry methods.

Our goal is to analyze aromaticity of the molecules 3, 4 and 5 (figure 1), and to explain

their stability, relative reactivity using molecular electrostatic potential (MEP) and local

ionization energy surfaces. For this purpose, DFT and ab-initio calculations would be

performed on these molecules. In terms of molecular surfaces based on electron density it is

possible to explain the aromatic behavior of these compounds. Optimized structures, atomic

charges, HOMO-LUMO gaps, global hardness, electronegativity index are also reported to

explain the behavior of these systems. The purpose of our work was to find reactivity

descriptors that explains and predicts the reactivity of these molecules and compare their

reactivity with that of furan and thiophene.

Figure 1. Studied molecules.

Geometry optimizations for compounds 1-5 (figure 1) were performed at both HF and

DFT level. The geometries 1-5 were fully optimized at the DFT B3LYP level of theory with a

6-31G* basis set.

Banjo Semire and Olusegun Ayobami Odunola 90

The basis set 6-31G* was used for all atoms in ab initio methods, this has been used by

several researchers in studying heterocycles (Romina et al, 2007; Bouzzine et al,2005;

Bouzzine et al, 2009; Armelin et al, 2009; De Olivera et al, 2004; Dkhissi et al, 2002 and

Amazonas et al, 2006). The images of MEP and ionization potential surfaces were obtained,

harmonic vibrational frequencies are positive. All calculations were performed using Spartan

06.

The stability and reactivity descriptors: total energy E, ionization energy I, absolute

hardness η, electrophilicity index ω, frontier molecular orbital energy gap ΔH-L of isomeric

heterocycles 1-5 calculated at the HF/6-31G* and DFT B3LYP 6-31G* levels of theory are

shown in the Table 1.

As shown in Table 1, the hardness and HOMO-LUMO gap as a characteristic of

reactivity shows that heterocycle 3 is expected to be more reactive than furan (1) and

thiophene (2) but less reactive than 4 and 5.

However, 5 would exhibit higher degree of reactivity and antiaromatic behavior in the

electrophilic reactions as compared to 4. The reactivity of the molecules studied are correlated

with the number of rings when thiophene is not included, there is an increase in electrophilic

character of the molecule with increase in number of rings (Figure 2).

The computed E for HF/6-31G* and DFT B3LYP 6-31G* methods shows that isomer 4

is more stable system than isomer 5.

The energy difference between isomers 4 and 5 is 4.58 Kcal/mol for B3LYP/6-31G*

calculation, and 6.15Kcal/mol for HF/6-31G* calculation (Figure 3 and 4).

The calculated values of global electrophilicity index ω show the nucleophility power of

heterocycles 1-5.

The ω values calculated with HF/6-31G* show that thiophene (2) has highest

electrophilic character but DFT results show that 4 and 5 are more electrophiles than 2. The

obtained ω values for 4 and 5 isomers are similar.

However, since heterocycle 4 exhibits a lower ω value of 0.17 eV (DFT) and 0.43 eV

(HF/6-31G*) as compared to 5, one could expect better propensity of 4 to be involved in the

reactions with electrophiles than for heterocycle 5 (Table 1).

Table 1. Global properties of heterocycles 1-5; μ, η, Δ H-L - frontier molecular orbital

energy gap calculated at HF/6-31G* and DFT-B3LYP/6-31G* (bracket) in eV

Compound HOMO LUMO Δ H-L Μ η ω

1 -8.66

(-6.11)

4.88

(0.54)

13.56

(6.65)

-1.89

(-2.79)

6.77

(3.33)

0.26

(1.17)

2 -8.94

(-6.34)

3.75

(-0.21)

12.69

(6.13)

-2.60

(-3.28)

6.35

(3.06)

0.53

(1.75)

3 -8.08

(- 5.23)

3.47

(-0.43)

11.55

(4.80)

-2.31

(-2.83)

5.78

(2.40)

0.46

(1.67)

4 -7.60

(-5.40)

3.28

(-0.57)

10.88

(4.83)

-2.16

(-2.99)

5.44

(2.42)

0.43

(1.84)

5 -7.52

( -5.36)

3.05

(-0.74)

10.57

(4.62)

-2.24

(-3.05)

5.29

(2.31)

0.47

(2.02)

Theoretical Study of Nucleophilic Behaviour ... 91

Figure 2. Relationship between number of rings in the molecule and electrophilicity index.

Figure 3. Calculated energy (Kcal/mol), dipole moment (Debye) and electrostatic potential

surfaces on the molecular surfaces of heterocycles 4 and 5 with HF/6-31G*. Color ranges, in

kJ/mol: from red -113.37 to blue +134.23 for 4 and from red -108.47 to blue +134.82 for 5.

Both DFT and Hartree Fock (HF) have been used to estimate the ionization energy I(r)

and molecular electrostatic potential (MEP) energy surfaces of heterocycles 4 and 5. The

visualized results of MEP energy and I(r) surfaces are shown in Figures 2, 3, 4.

Banjo Semire and Olusegun Ayobami Odunola 92

Figure 4. Calculated energy (Kcal/mol), dipole moment (Debye) and electrostatic potential

surfaces on the molecular surfaces of heterocycles 4 and 5 with BLY3P/6-31G*. Color ranges, in

kJ/mol: from red -196.06 to blue +118.66 for 4 and from red -93.26 to blue +116.48 for 5.

The presented MEP surface, an overlaying of the electrostatic potential (the attraction or

repulsion of a positive charge for a molecule) is valuable for describing overall molecular

charge distribution as well as anticipating sites of electrophilic addition. The red color

represent negatively charged areas of surface (i.e. those areas where accepting an electrophile

is most favorable). Another indicator of electrophilic attraction is provided by the local

ionization potential energy surface, an overlaying of the energy of electron removal

(ionization) onto the electron density. The regions with red color represent regions in the

molecular surface where electron removal goes (with minimal energy) most easily.

The difference in reactivity of heterocycles 4 and 5 can be judged from the values of

electrostatic potential and local ionization energy surfaces presented in Figures 4, 5.

For heterocycle 4 the lowest local ionization energy values and negatively charged

electrostatic potential values are found on the C(1)=C(2) and C(1*)=C(2*) bonds and

delocalization of π–electron on thiophene ring spreading over C(1)=C(2) and C(1*)=C(2*)

bonds of furan rings, therefore 4 is more stabilized and aromatic by thiophene ring at the

middle of the heterocycle. This suggests that molecule 4 would involve in the electrophilic

substitution via addition-elimination mechanism.

Theoretical Study of Nucleophilic Behaviour ... 93

Figure 5. Calculated local ionization energy surfaces on the molecular surfaces of heterocycles 4

and 5 with B3LYP/6-31G*. Color ranges, in kJ/mol: from red 8.37 to blue 16.14 for 4 and from

red 8.62 to blue 15.48 for 5.

On the contrary the electrostatic potential and local ionization energy surfaces for

heterocycle 5 shows delocalized π–electron surface on thiophene rings and also localized

charge on C(2) of furan ring. This result suggests the presumable possibility of aromatic

electrophilic substitution mechanism reactions of heterocycle 5 on C(1*)=C(2*) of thiophene

ring and addition-elimination reaction mechanism at position C(2).

The frontier molecular orbital pictures of the both molecules 4 and 5 are shown in Figure

6. Only the HOMO, HOMO-1 and LUMO are presented in this work. The energy difference

between the HOMO and HOMO-1 for 4 is smaller than for 5 by 0.23 eV. For the heterocycles

4 and 5 the π molecular orbital localization exists between furan and thiophene rings

accordingly as shown in HOMO shapes. For both molecules, the greatest extension value of

HOMO is observed on C(1) and C(1*) atoms. Moreover for 4 the HOMO-1 is delocalized on

C(2)-CS=C(3)-C(3*)=CS-C(2*) bonds with largest value on C(3)-C(3*) bond while for 5 the

HOMO-1 shape is majorly delocalized on C(3)-C(3*)=CS-C(2*) bonds.

With this molecular orbital analysis the relative reactivity can be explained, the π

molecular orbital delocalization agrees well with the reactivity behavior of heterocyclic rings.

The greatest extension value of HOMO shape on C(1) and C(1*) atoms suggest exceptional

reactivity of this atoms (because of the symmetrical nature of the molecules) in the

electrophilic reactions.

Banjo Semire and Olusegun Ayobami Odunola 94

Figure 6. HOMO, HOMO-1, LUMO orbitals for heterocycles 1 and 2 calculated using B3LYP/ 6-

31G*.

Mulliken charge population at HF/6-311G* and DFT B3LYP 6-311G* levels show very

similar reactivity descriptor values considering reactivity tendencies.

The two methods used in the present work (DFT and HF) for calculation of Mulliken

charge population lead to the same qualitatively and quantitatively similar description of the

chemistry and reactivity of the heterocycles 4 and 5. The negative charge increase in

molecule represents the attraction of relevant sites of molecule in reactions with electrophiles.

The highest negative charge located on C(2),C(2*) atom of heterocycle 4, so Mulliken

charges calculated at both HF and DFT for 4 suggest that electrophilic reaction could occur

with this carbon atom. For heterocycle 5, the highest negative charges are on C(2), C(1*) and

C(2*). This suggests that electrophilic reaction could occur with these carbon atoms, however

the most probable atom for electrophilic reaction is C(1*) in molecule 5 (Table 2). These are

in agreement with analysis of MEP, I(r) and HOMO shapes.

Table 2. Mulliken charges on selected atoms of heterocycles 4 and 5 calculated with

HF/6-31G* and B3LYP/6-31G*

Atom Heterocycle 4 Heterocycle 5

HF/6-31G* B3LYP/6-31G* HF/6-31G* B3LYP/6-31G*

C(1),C(1*)

C(2),C(2*)

-0.116

-0.263

0.088

-0.209

0.102, -0.435

-0.256, -0.150

0.059, -0.371

-0.192, -0.105

Theoretical Study of Nucleophilic Behaviour ... 95

CONCLUSION

A theoretical study of the stability and reactivity was carried out at the density functional

theory and ab-initio calculation level for the structures of furan, thiophene, thieno[3,2-

b]furan, 3,4-Dioxa-7-thia-cyclopenta[a]pentalene and 3,7-Dioxa-4-thia-cyclopenta[a]

pentalene. Global descriptors such as chemical potential (μ), molecular hardness (η),

electrophilicity (ω), frontier molecular orbital (HOMO-LUMO) energy gap, local ionization

energy and electrostatic potential energy surfaces were determined and used to identify the

differences in the reactivity of heterocycles.

The hardness and HOMO-LUMO gap as a characteristic of reactivity shows that

heterocycle 3 is expected to be more reactive than furan (1) and thiophene (2) but less

reactive than 4 and 5. However, 5 would exhibit higher degree of reactivity and antiaromatic

behavior in the electrophilic reactions as compared to 4.

REFERENCES

Amazonas, J. G.; Guimaraes, J. R.; Santos Costa, S. C.; Laks, B.; Del Nero, J.; Theoretical

modeling of low band-gap organic oligomers, J. Mol. Struct. [THEOCHEM] 2006, 759,

87–91.

Armelin, E., Bertran, O., Estrany, F., Salvatella, R and Alemán, C. Characterization and

properties of a polythiophene. Euro Polymer J. 2009, 45, 2211-2221.

Biolatto, B.; Kneeteman, M.; Mancini P. Diels-Alder reactions of N-tosyl-3-nitroindole and

dienamides: Diels-Alder reactions of N-tosyl-3-nitroindole and dienamides: synthesis of

intermediates of Aspidospermine alkaloids. Tetrahedron Lett. 1999, 40, 3343-3446.

Bird, C.W. Heteroaromaticity. 10. The Direct Calculation of Resonance Energies of Azines

and Azoles from Molecular Dimensions. Tetrahedron. 1997, 53, 2497-2501.

Bouzzine, S. M. Hamidia, M and Bouachrine M. DFT study of bridged oligo(bithiophene)s.

Conformational analysis and opto-electronic properties Orbital. 2009, 1, 203-210.

Bouzzine, S.M., Bouzakraoui, S., Bouachrine, M and Hamidi. M. Density functional theory

(B3LYP/6-31G*) study of oligothiophenes in their aromatic and polaronic states, J. Mol.

Struct. [THEOCHEM] 2005, 726, 271-276.

Brasca, R.; Kneeteman, M. N.; Pedro M.E. Calculation of electronic properties of aromatic

dienophiles for reactivity prediction in diels-alder reactions, IDECEFYN. 2007, 12, 54-57

Chamizo, J. A.; Morgado, J.; Sosa, O. Organometallic Aromaticity, Organometalliks. 1993,

12, 5005-5007.

De Olivera, M.A., De Almeida, W.B and Dos Santon, H.F. Structure and electronic properties

of alkylthiophenes coupled by Head-to-Tail and Head-to-Head regioselectivity J. Braz.

CHem. Soc. 2004, 15, 832-839.

Della Rosa, C.; Paredes, E.; Kneeteman, M. N.; Mancini, P. M. E. 2-Nitrofurans as

dienophiles in Diels-Alder reactions. 8th International Electronic Conference on

Synthetic Organic Chemistry (ECSOC-8), 2004, A016.

Dkhissi, A.; Belijonne, D.; Lazzaroni, R.; Louwet, F.; Groenendeal, L.; Bredas, J.L. Density

functional theory and Hartree–Fock studies of the geometric and electronic structure of

neutral and doped ethylenedioxythiophene (EDOT) oligomers, Int. J. Quant. Chem. 2002,

91, 517-523.

Banjo Semire and Olusegun Ayobami Odunola 96

Domingo, L. R.; Aurell, M.; Contreras, M.; Perez, P. Quantitative Characterization of the

Local Electrophilicity of Organic Molecules. Understanding the Regioselectivity on

Diels−Alder Reactions, J. Phys. Chem. A. 2002, 106, 6871-6876.

Ehresmann, B.; Martin, B.; Horn, A. H.C.; Clark, T. Local molecular properties and their use

in predicting reactivity. J. Mol. Model. 2003, 9(5), 342-347.

Koopmans, T. Ordering of wave functions and eigenvalues to the individual electrons of an

atom, Physica. 1934, 1, 104-113.

Parr, R.G.; Szentpaly, L.; Liu, S. Electrophilicity Index, J. Am. Chem. Soc. 1999, 121, 1922-

1924.

Pearson, R. G. (1993) The principle of maximum hardness, Acc. Chem. Res, 26(5), 250-255.

Politzer, P.; Truhlar, D.G. (eds) Chemical applications of atomic and molecular electrostatic

potentials: Reactivity, structure, scattering, and energies of organic, inorganic, and

biological systems. Plenum, New York (1981).

SPARTAN 06, Wavefunction Inc., Irvine, CA, 92612.

Zhou, Z; Navangul, H. V. Absolute hardness and aromatisity: MNDO study of benzenoid

hydrocarbons, J. Phys. Org. Chem.1990, 3, 784-788.