obtained by Ray X diffraction

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

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

Structural and Vibrational Properties and NMR Characterization of (2'-furyl)-Imidazole Compounds 175

HOMO -0.21 -0.22 -0.19 -0.19 -0.18 -0.18 -0.19 -0.19 LUMO -0.01 -0.01 -0.01 -0.01 0.00 0.00 -0-01 -0-01 GAP 0.20 0.20 0.17 0.17 0.18 0.18 0.17 0.17

(kJ/mol) 535.0 542.9 464.2 464.2 495.4 495.4 466.8 466.8

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

All nuclear magnetic resonance spectra were recorded for diluted solutions in DMSD-d6 and the calculated chemical shifts of the 1H NMR and 13C NMR for the two conformers of each compound were obtained by GIAO method24 using the B3LYP/6-311++G\*\* theory level, as it is usually used for chemical shift NMR calculations on reasonably large molecules25,26. 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 13C 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

The peak belonging to H atom of the N–H bond appears at 11.37 ppm. A small shift of these peaks towards lower fields implies the existence of some intermolecular interaction between

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

*syn anti syn anti syn anti syn anti* 

4-(2'-furyl)- Imidazole

5-(2'-furyl)- Imidazole

2-(2'-furyl)- Imidazole

Orbital N-(2'-furyl)-

GAP

of the series

Imidazole

**2.2 Nuclear magnetic resonance characterization** 

accurately description of the current density17,18.

nonbonding electrons.

24 Ditchfield, 1974. 25 Cheeseman et al., 1996. 26 Keith Bader, 1993.

other 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.

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

#### **2.2 Nuclear magnetic resonance characterization**

All nuclear magnetic resonance spectra were recorded for diluted solutions in DMSD-d6 and the calculated chemical shifts of the 1H NMR and 13C NMR for the two conformers of each compound were obtained by GIAO method24 using the B3LYP/6-311++G\*\* theory level, as it is usually used for chemical shift NMR calculations on reasonably large molecules25,26. 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 13C 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 density17,18.

The peak belonging to H atom of the N–H bond appears at 11.37 ppm. A small shift of these peaks towards lower fields implies the existence of some intermolecular interaction between nonbonding electrons.

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

174 Magnetic Resonance Spectroscopy

other 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.

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.

<sup>24</sup> Ditchfield, 1974.

<sup>25</sup> Cheeseman et al., 1996.

<sup>26</sup> Keith Bader, 1993.

Structural and Vibrational Properties and NMR Characterization of (2'-furyl)-Imidazole Compounds 177

 Exp.b Theorc Exp.b Theorc 10 104.3 103.55 6.54 (d, J=3.3 Hz, 1H) 6.29 11 111.3 108.82 6.43 (dd, J=1.8, J=3.3 Hz, 1H) 6.17 5 114.7 111.03 7.33 (d, J=0.9 Hz, 1H) 6.98

12 135.6 138.1 7.71 (d, J=0.9 Hz, 1H) 7.26 2 141.2 141.35 7.39 (dd, J=0.9, J=1.5 Hz, 1H) 7.16

N-H 11.37 (bs,1H) 7.86

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 8 and 9, respectively. The calculation results show that the GIAO method reproduces quite well the 13C and 1H 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

Chem. Shifts C10 C11 C5 C4 C12 C2 C6 RMSD

*anti* b 96.5 112.7 117.7 133.2 135.4 140.4 149.5 *0.9 syn* b 93.6 112.7 116.1 132.9 134.7 139.1 149.7 *0.9*  **AVERAGEB** 95.0 112.7 116.9 133.1 135.0 139.7 149.6 *0.9* 

Table 8. 13C Experimental and calculated Chemical shifts (in ppm) for N-(2'-furyl)-imidazole

Chem. Shifts H14 H15 H8 H9 H16 H7 RMSD

*anti* b 5.87 6.29 7.05 7.05 7.16 7.30 *0.10 syn* b 5.73 6.28 6.81 7.01 7.08 7.62 *0.10*  **AVERAGE**B 5.80 6.29 6.93 7.03 7.12 7.46 *0.09* 

Table 9. 1H Experimental and calculated Chemical shifts (in ppm) for N-(2'-furyl)-imidazole

Exp.a **6.14 6.44 7.13 7.22 7.26 7.81** 

Exp.a 96.2 111.6 117.5 130.0 135.4 138.9 144.5

Position C H, multiplicidad in ppm

4 131.6 132.40

8 149.0 153.20

conformers are present in the solution.

a Related to DCCl3; b GIAO, B3LYP/6-311++G\*

a Related to DCCl3; b GIAO, B3LYP/6-311++G\*

a B3LYP/6-311++G\*\*, average values; b In CDCl3; c Related to TMS

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 13C and 1H 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 CDCl3 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.

