Structural and Vibrational Properties and NMR Characterization of ( 2 ’-furyl )-Imidazole Compounds

Ana E. Ledesma1, Juan Zinczuk2, Juan J. López González3 and Silvia A. Brandán4* 1INQUINOA-UNSE, Facultad de Agronomía y Agroindustrias, Universidad Nacional de Santiago del Estero, Santiago del Estero 2Instituto de Química Rosario (CONICET-UNR), Facultad de Ciencias Bioquímicas y Farmacéuticas, Rosario, Santa Fé 3Departamento de Química Física y Analítica, Facultad de Ciencias Experimentales, Universidad de Jaén, Jaén 4Cátedra de Química general, Instituto de Química Inorgánica, Facultad de Bioquímica, Química y Farmacia, Universidad Nacional de Tucumán, San Miguel de Tucumán, Tucumán, República 1,2,4Argentina 3Spain


Introduction
The furylimidazoles compounds have a great importance in biochemistry and pharmacology because many of them present interesting properties 1,2 .They are also found in artificial compounds 3 , such as agrochemicals, 4 pharmaceuticals 5 , dyes 6 , plastics, solvents, photographic chemicals, electronics, corrosion inhibitors, 7 preservatives, and polymers 8 .They can be used in synthetic organic chemistry as building blocks, due to their presence as key structural units in many natural products and in important pharmaceuticals.For example, the nature of the N-atoms in the imidazole molecule makes possible an extraordinary variety of reactions and this is the main reason for the great biological importance of the amino acid, histidine.
Polymers of these compounds, which have potential as semi-conducting material are of great importance, because of their good thermal and chemical stability and relative ease of functionalization, which potentially permit the fine tuning of their physical and electronic properties 9 In fact, these compounds provide one of the best studied examples of annular tautomerism, such as the 4(5)-substituted imidazoles 10,11,12 .Recently, the theoretical and experimental studies on structure, electronic and vibrational properties for the (2'-furyl)-imidazole series were reported by us 13,14,15,16,17 .
Examination of the spectroscopic data for the each furanics molecules indicated that Nuclear Magnetic resonance spectroscopy, coupled with IR spectroscopy, was potentially the best analytical technique to provide confirmatory structural evidence for their formation.On the other hand, in general, the chemical shifts for the substituted imidazole ring, relative to the unsubstituted rings, suggest that the mesomeric effect of the five-membered rings contributes less to the interaction between two rings than does their inductive effects.It would indicate which rings is more electron-withdrawing in its overall electronic effect than the furan ring, as well as observed in the pyridine-thiophenes and furans 18 .The downfield shifts of the 13 C NMR signals for the carbon atom at the point of substitution on the imidazole ring would be explicate of the significant inductive electron-withdrawing effects of the 2-heteroaryl rings.
For this, reason for predicting the reactivity of this molecules due to the different position of the substituent, in this chapter, a comparison of the structural and vibrational properties of the four molecules belong to the (2'-furyl)-imidazole series was performed in order to evaluate the experimental and theoretical results based on B3LYP calculations by using 6-31G* and 6-311++G** basis sets.The optimized geometries and frequencies for the normal modes of vibration were calculated using both theory levels.For a complete assignment of the compounds, the DFT (Density functional Theory) calculations were combined with the scaled quantum mechanical force field (SQMFF) methodology 19,20,21 in order to fit the theoretical wavenumbers to the experimental ones.In all molecules of this series, the changes in the chemical shifts of the hydrogen and carbon atoms were also studied.In addition, the electronic properties of those molecules were evaluated by means of natural bond orbital (NBO) and atoms in molecules (AIM) studies in order to analyze the nature and magnitude of the intramolecular interactions.In this chapter, the experimental and theoretical studies of

Structure and properties of the (2'-furyl)-imidazole series 2.1 Structural analysis
All compounds of this series are present in two different stable conformations according to the syn and anti position of the oxygen atom with respect to the N-H bond, named syn and anti conformers, respectively, as show in Figure 1.Experimentally, all molecules of this series have different characteristics or they are solid of different nature.Thus, the first series's member, N-(2'-furyl)-imidazole, is a liquid at room temperature and probably the two conformers are present in it.For the second series's member, 2-(2'-furyl)-imidazole, the crystallography analysis shows that both conformers are present in the crystalline lattice with equal occupancy and alternated arrangement in the N-H---N bonded polymeric chains along the crystal  Table 1 shows a comparison of the total energy and dipole moment values for all molecules by using the 6-31 and 6-311++G** basis sets at B3LYP theory level.Note that all predicts values are similar between them and, only for the N-(2'-furyl)-imidazole, the calculation predicts that the anti conformation is the most stable, while that for the remaining compounds the syn conformation is the most stable.
The comparison between the experimental geometrical parameters (obtained for 2-(2'-furyl)imidazole) with the corresponding theoretical values are shown in Table 2.The analysis shows that the length of C=C bond of the furan ring, does not change for all molecules, while the length of C=C bond of the imidazole ring varies according the following order: (4)5-(2'-furyl)-imidazole > N-(2'-furyl)-imidazole > 2-(2'-furyl)-imidazole.This trend is explained taking into account the next of this bond respect to the furan ring, since in the first molecule that bond is in alpha position respect to C=C bond corresponding to the furan ring, favoring the electronic delocalization, while in the remaining structures those bonds Unit 2 Unit 1 Unit 3 are in beta and gamma positions, respectively.This effect also explains the observed tendency for the C-N bond next to furan ring.

N-(2'-furyl)-imidazole
Conf.Another very important difference between all series members is related to the dihedral angles.Thus, the angles values are 180° and 0° for the 2 and 4(5) isomers, while for the first isomer those values are between 30-40° and 160-170° respectively.
The stability of the different conformers were investigated using the Electrostatic Surface Potential, ESP maps 22,23 because these surfaces are important for describing overall molecular charge distributions as well as anticipating sites of electrophilic addition 23 .The molecular ESP values for the anti and syn conformers of each member's series by using 6-31G* basis set are given in Table 3 while Figure 3 shows the ESP maps for all conformers of this series.The red color represents negatively charged areas of the surface (i.e., those areas where accepting an electrophile is most favorable).The atomic charges derived from the ESPs (MK) and natural atomic charges were also analyzed and the corresponding values are given in Table 4.Note that the most important differences in all cases are observed on the imidazole ring.The important factor responsible for the lesser stability of same conformer is the electrostatic repulsion between the two lone pairs on N and O. Hence, a strong red color on both atoms is observed in the corresponding Figure 3  For the N-(2'-furyl)-imidazole a region can be observed where the delocalization of charge decrease (blue region between two rings) due to the breaking-off planarity of the both rings, while the remain molecules show π-electron delocalizated surfaces that evidence stables aromatic systems, being smaller for the N-(2'-furyl)-imidazole compound.
These results can be related with the energies of the HOMO and LUMO for all molecules.Table 4 shows the comparison of the HOMO and LUMO orbitals energies values as well as the GAP energies values of them.
The corresponding values for the N-(2'-furyl)-imidazole show that this compound is the most stable of the series, as expected, because it presents the longer GAP values.On the www.intechopen.comother hand, the calculated energy HOMO orbital value for 4-(2'-furyl)-imidazole is higher than the other ones due to the fact that it is the most reactive compound of this series.

Nuclear magnetic resonance characterization
All nuclear magnetic resonance spectra were recorded for diluted solutions in DMSD-d 6 and the calculated chemical shifts of the 1 H NMR and 13 C NMR for the two conformers of each compound were obtained by GIAO method 24 using the B3LYP/6-311++G** theory level, as it is usually used for chemical shift NMR calculations on reasonably large molecules 25,26 .The calculations have been performed using the geometries optimized for this theory level and by using TMS as reference.A comparison of the results is present in Table 5 and it shows that for 2-(2'-furyl)-imidazole the calculated 13 C chemical shifts from CSGT method are in accordance with the experimental values, while the closest values were obtained with the GIAO method and the 6-311++G** basis set.Furthermore, the calculated shifts with both methods for the C(2), C (7), and C(1) atoms are higher than the experimental values.One important observation is that the results obtained from the conformational average have better agreement with data experimental, as expected, due to the presence of the two conformers in the solution.On the other hand, a comparison is present in Table 6 and it shows the calculated shifts with the two methods used where, for the H atom show significant differences with the experimental results.The addition of the polarization and diffuses functions at the basis set improves the results; however, the CSGT method predicts shifts practically different than the GIAO method for this atom.This disparity would be attributed to the fact that the GIAO method uses basis functions which depend on the field while the CSGT method achieves gauge invariance by performing a continuous set of gauge transformations, for each point, obtaining an accurately description of the current density 17,18 .
The peak belonging to H atom of the N-H bond appears at 11.37 ppm.C and 1 H atoms, respectively.The agreement with our experimental data in these solvents is good, except for the H atom of the H-N bond in chloroform.This is because the calculations are for the gas phase, while the experimental values are for the CDCl 3 solution, where the molecular interactions are important.It is important to mention that the registered NMR spectra at room temperature and low temperature were not sufficient to identify the tautomeric mixture of 1, because the speed of exchange of protons is higher than the response time of NMR.

Vibrational analysis
For this analysis the vibrational frequencies were separated in two groups, the first group corresponds to the skeletal vibrations ring and the second ones to those vibrations related to the C-H groups, both are show in Tables 10 and 11, respectively.The analysis shows that the frequencies values for the C=C stretching of the imidazole ring is according to the respective length bonds.Furthermore, the frequencies values for the C=N stretching mode are longer for the N-(

Conclusions
All compounds studied in this chapter were synthesized and only, the 2-(2'-furyl)-1Himidazole compound was isolated as a crystalline solid, which allowed the molecular structure's determination by means of the ray X diffraction.In all cases, the theoretical method that better reproduces the experimental data is the B3LYP/6-311++G** combination, for this, the calculated molecular geometries and vibrational spectra were performed at this theory level.Each molecule presents two stable conformations, anti and syn, according to the orientations of the furan and imidazole rings.The calculations predicted that the conformation syn is the most stable, with exception of the isomer one, for which the anti conformer was the most stable.The distances among both rings only present appreciable changes for the isomer one which because the union in this case is by means of the C-N instead C-C like in the remaining ones.In the 4(5)-(2'-Furyl) Imidazole isomers, the infrared spectra at low temperature allowed the complete assignment of the both member's series.
The PEM analysis shows that when the -electron delocalizated surface is longer, the hydrogen atoms are less retained by the carbon atoms and, for this reason, an increasing in the respective length bonds is observed.Due to this, the H atom is very labile in consequence can be easily substituted.The later behavior is observed when the frequencies of the C-H groups in the N-(2'-Furyl)-imidazole are analyzed in reference to the other compounds of this series.Finally, the N-(2'-Furyl)-imidazole compound is the most stable member of the series.

Fig. 1 .
Fig. 1.Molecular structures of the (2'-furyl)-imidazole series [101] direction.Only three units of the polymeric structure are shown in Figure 2. Finally, the 4-(2'-furyl)-imidazole and 5-(2'-furyl)-imidazole compounds are present in a tautomeric mixture in the solid state as a white power.The calculation indicates that both conformers of N-(2'-furyl)-imidazole have C 1 symmetries, in the 2-(2'-furyl)-imidazole they have C 1 and C s symmetries, while in the remaining molecules all conformers present C s symmetries.

Fig. 2 .
Fig. 2. View of a N-H---N bonded polymer chain in solid 2-(2'-furyl)-imidazole.The central monomer is related with the right and left side monomers through a crystallographic inversion center and a two fold axis rotation, respectively.The H-bonding is indicated by dashed lines

Fig. 3 .
Fig. 3. Electrostatic Surface Potential calculated on the molecular surface of the conformers for all compounds of the series.Color, in u.a.: from red -0.103 to blue 0.103. .

Table 2 .
Geometrical parameters for all compounds of the series www.intechopen.comStructural and Vibrational Properties and NMR Characterization of (2'-furyl)-Imidazole Compounds 173

Table 3 .
Molecular electrostatic potentials for all members of the series calculated at B3LYP/6-31G* level of theory

Table 4 .
HOMO and LUMO orbitals Energíes (u.a.) and gap of energy (u.a.) for all members of the series

Table 7
shows the experimental and calculated chemical shifts for 4(5)-(2'-furyl)-imidazole.These chemical shift values indicate that in the H atom is weakly held by two imidazole rings.At an intermediate rate of exchange, the H atom is partially decoupled, and a broad N-H peak results.The most intense peak of this spectrum belongs to the C atom of the reference, while the following four peaks belong to the C atoms of the furyl group.The calculated chemical shifts are in agreement with the experimental ones, with RMSD values of 2.53 and 0.32 ppm for the

Table 6 .
The experimental and calculated 1 H chemical shifts in ppm

Table 7 .
Experimental and calculated Chemical shifts (in ppm) for 4(5)-(2'-furyl)-imidazole A comparison between the experimental and calculated chemical shifts for the C and H atoms for N-(2'-furyl)-imidazole are given in Tables

Table 9 .
1 and1H experimental chemical shifts values as shown by the calculated root mean square deviations (RMSD) values for each conformer.Furthermore, the shifts of the H atoms for both structures are similar in both conformers and practically equal to the average values.As expected, the latter values have a better agreement with the experimental data, probably because both conformers are present in the solution.

Table 10 .
2'-furyl)-Imidazole, due to the highest p character of bound, which impedes the resonance effects between two rings.Changes in the frequencies values related to the C-O stretching modes are not observed, in accordance with the corresponding length bonds, where the variations were only observed for the imidazole ring.The vibrational ring modes are practically observed in the same region for all series molecules, while the corresponding torsions are in agreement with the imidazole ring in all series members and they are next to the reported values for the imidazole compound.Experimental Vibrational Frequencies for all modes of imidazole and furan rings of the series.A notable difference between the frequencies of the C-H stretching modes is observed.The rotating of the imidazole ring with the furan ring increase or decrease the frequencies assigned to the alilic hydrogen.

Table 11 .
Experimental vibrational frequencies for C-H groups