J. Chil. Chem. Soc., 48, N 2 (2003)

Eduardo Sobarzo-Sánchez*^,1, Claudio Olea-Azar*^,1, Jaime Alarcón², Lucía Opazo²
and Bruce k. Cassels ¹

¹ Department of Chemistry, Faculty of Sciences, and Millennium Institute for Advanced Studies in Cell Biology and Biotechnology, Universidad de Chile, Casilla 653, Santiago, Chile. E-mail: esobarzo@usc.es
² Department of Inorganic and Analytical Chemistry, Faculty of Chemical and Pharmaceutical Sciences,
Universidad de Chile, Casilla 233, Santiago 1, Chile. E-mail: colea@uchile.cl
( Received : January 29, 2003 ­ Accepted : March 18, 2003)

ABSTRACT

The electrochemical behavior of two representative 2,3-dihydro-7H-dibenzo[de,h]quinolin-7-ones was determined using cyclic voltammetry in DMSO as solvent and rationalized by quantum chemical calculations using ab initio and DFT methods. The ESR spectra of the radicals obtained by electrolytic reduction were characterized and analyzed. Calculations at the HF/3-21G and DFT-B3LYP/6-311++G** levels were carried out to obtain the optimized structure, hyperfine coupling constants and to determine the values and to visualize the LUMO and SOMO energy levels, respectively. The calculated electron affinities are in agreement with the reduction potentials measured for both heterocyclic compounds.

KEYWORDS: dihydrooxoisoaporphines, 7H-dibenzo[de,h]quinolin-7-ones, cyclic voltammetry, ESR, anion radical, DFT.

INTRODUCTION

A small group of oxoisoaporphine-type alkaloids possessing the 7H-dibenzo[de,h]quinoline skeleton and bearing different substitution patterns have been isolated from Menispermum dauricum DC. (Menispermaceae).¹⁾ These isoquinoline alkaloids are present in small quantities, making their isolation and reactivity studies difficult. However, compounds with the same skeleton, known as azabenzanthrones, had been synthesized earlier due to their possible photo- and electrochemical properties,²⁾ and as intermediates for the formation of dyes.³⁾ More recently, the synthesis of 7H-dibenzo[de,h]quinolin-7-one derivatives through the cyclization of N-phenethylphthalimides afforded a new way to obtain these compounds.⁴⁾ A number of 2,3-dihydrooxoisoaporphine derivatives have also been prepared by cyclization of 3-(b-dialkoxyarylethylamino)phthalides with polyphosphoric acid (PPA).⁵⁾ However, the "isoaporphines", their hypothetical 7-deoxo-1,2,3,4-tetrahydro counterparts, have not been found as natural products and do not seem to have been obtained synthetically. We have therefore sought an explanation for their apparent non-existence in nature by studying the reduction of oxoisoaporphines and their dihydro derivatives.

By means of the synthetic route mentioned above,⁵⁾ we were able to obtain sufficient quantities of oxoisoaporphine derivatives to study their cathodic behavior. Thus, the electrochemical reduction of a couple of 2,3-dihydrooxoisoaporphines was studied using cyclic voltammetry (CV) with DMSO as solvent under a nitrogen atmosphere. Also, in order to complement recent studies on the photoreduction of dihydrooxoisoaporphines,⁶⁾ we have recorded the generation of the corresponding radical anions through Electron Spin Resonance (ESR) and analyzed the spectra. Calculations of the hyperfine coupling constants were carried out using density functional theory (DFT) at the B3LYP/6-311++G** level. The electron affinities (EA) were calculated at the ab initio 3-21G and DFT-B3LYP/6-311++G** levels. The appearance of the SOMO (Singly Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital), depicted on the basis of these theoretical calculations, is shown and discussed. The optimized structures of 1 and 2 were obtained at the ab initio 3-21G level.

EXPERIMENTAL

Samples. In order to carry out these studies, 2,3-dihydro-5-methoxy-7H-dibenzo[de,h]quinolin-7-one (1) and 5-methoxy-6-hydroxy-2,3-dihydro-7H-dibenzo[de,h]quinolin-7-one (2) were synthesized as starting materials (Figure 1).

Figure 1. Chemical structures of the 2,3-dihydrooxoisoaporphine derivatives studied.

Cyclic Voltammetry. The DMSO (spectroscopy grade) was supplied by Aldrich. The tetrabutylammonium perchlorate (TBAP) used as supporting electrolyte was purchased from Fluka. Cyclic voltammetry was carried out using a Weenking POS 88 instrument with a Kipp Zenen BD93 recorder, in DMSO (ca 1.0 x 10^-2 mol dm^-3), under a N₂ atmosphere, with TBAP (ca 0.1 mol dm^-3), using three-electrode cells. A dropping mercury electrode was used as the working electrode, a platinum wire as the auxiliary electrode, and saturated calomel as the reference electrode.

ESR Spectroscopy. The free radicals of compounds 1 and 2 were generated by electrolytic reduction in situ at room temperature.

ESR spectra were recorded in the X band (9.85 GHz) using a Bruker ECS 106 spectrometer with a rectangular cavity and 50 KHz field modulation. The hyperfine splitting constants were estimated to be accurate within 0.05 G.

Theoretical Calculations. The optimized geometries in spin-paired and free radical forms were carried out at the ab initio 3-21G level. Single Point (SP) analysis of the optimized structures was later used to calculate and to visualize the SOMO and LUMO, hyperfine coupling constants and electron affinities at the DFT-B3LYP/6-311++G** level. All calculations were done employing the open shell UHF option implemented in Gaussian 98.⁷⁾

RESULTS AND DISCUSSION

CYCLIC VOLTAMMETRY

Compounds 1 and 2 were studied by CV, determining the cathodic peak current (Epc) and comparing the values with the LUMO obtained through different ab initio and DFT calculations summarized in Table 1.

Table 1. Cyclic voltammetry parameters of 1 and 2 versus LUMO energies calculated at the HF/3-21G and DFT-B3LYP/6-311++G** levels. Sweep rate = 2000 mV/s in DMSO versus saturated calomel electrode (SCE).

It can be seen that two electrochemical couples are generated and characterized, the first being a quasi-reversible couple in agreement with the formation of a stable semiquinone radical anion at room temperature (Figure 2).

Figure 2. Isolated first couple at different sweep rates.

The intensity ratio ipa/ipc has a value close to one. According to standard reversibility criteria, this couple corresponds to a quasi-reversible diffusion-controlled one-electron transfer.^8,9) The second, irreversible couple, should correspond to the formation of a hydroquinone-type species, actually a 4-aminophenol, in the whole range of sweep rates used (100-2000 mV/s) (Figure 3).

Figure 3. Cyclic voltammetry of 2,3-dihydrooxoisoaporphine 1 in DMSO at different sweep rates.

With these electrochemical results, we can affirm that the oxoisoaporphines prefer to be in their more stable oxidized state, and understand why after reduction in the presence of oxygen they are reoxidized to the starting iminoquinone framework. In this way, we come closer to an explanation of the non-existence of the reduced heterocycles in nature and the failure to prepare them in the laboratory.

ELECTRON SPIN RESONANCE

The ESR spectrum of 2 (Figure 4) clearly shows the spin delocalization in the reduced radical.

Figure 4. a) ESR spectrum of 5-methoxy-6-hydroxy-7H-dibenzo[de,h]quinolin-7-one 2. 00000000b) Computer simulation of the same spectrum.

The interpretation of the ESR spectra of 1 and 2 by means of a simulation process led to the determination of the coupling constants for all magnetic nuclei and their comparison with theoretical calculations.

Molecule 2 presented a well resolved hyperfine splitting pattern. This spectrum was simulated in terms of five doublets due to hydrogens H₈, H₉, H₁₀ and H₁₁ of ring D. In the case of 1, H₆ was also considered, and 6-OH in the case of 2. Moreover, a triplet can be attributed to the nitrogen nucleus of the oxoisoaporphine skeleton. The hyperfine coupling constants are listed in Table 2.

Table 2. Experimental (DMSO) and calculated DFT-B3LYP/6-311++G** hyperfine splitting constants (Gauss) for the dihydrooxoisoaporphine anion radicals.

Molecule 1 did not give a well resolved ESR spectrum. However, it is possible to observe two groups of lines suggesting that the larger hyperfine constant should be due to a hydrogen nucleus on ring D, which we assign as H₁₀ (ESR spectrum not shown). In Table 2 we only present this experimental hyperfine constant for 1.

THEORETICAL CALCULATIONS

The completely optimized (HF/3-21G) structures of both electron-paired and anion radical forms of 1 and 2 were used to determine the hyperfine coupling constants and electron affinities, at the SP DFT-B3LYP/6-311++G** level, shown in Tables 2 and 3, respectively. These results are in agreement with the assignment of the hyperfine coupling constants and with the ability of 2 to be reduced more easily than 1 (Epc = -0.920 V and -1.170 V, respectively).

Table 3. Electron affinities (eV) calculated at the ab initio 3-21G and DFT-B3LYP/6-311++G** levels and cathodic peak currents (Epc) (in DMSO).

We attribute the latter effect to keto-enol tautomerism that increases the stabilization of the anion radical by intramolecular hydrogen bonding.

When we analyze the LUMO of 1 and 2 at the HF/3-21G and B3LYP/6-311++G** levels, we can see a radical anion stabilization of 2 with regard to 1 that can be related to hydrogen bonding between 6-OH and C=O. However, when the SOMOs of these two dihydrooxoisoaporphines are visualized, we see that the spin distribution in both free radicals is extended to the whole aromatic system, but localized prefentially on the quaternary carbon atoms forming ring C (Figure 5).

Figure 5. Visual representation of Singly Occupied Molecular Orbitals (SOMOs) of 1 and 2.

The SOMOs of 1 and 2 show that the electron spin density is interrupted on rings B and D due to the existence of nodes at C3a and C11.

CONCLUSIONS

The dihydrooxoisoaporphines 1 and 2 showed similar electrochemical behavior in DMSO. Both presented a first quasi-reversible couple due to formation of the semiquinone stable radical anion and a second irreversible couple attributed to the formation of a 4-aminophenol hydroquinone analog that is easily oxidized to the starting material. The interpretation and simulation of the ESR spectrum of 2 was obtained due to the strong stabilization of the generated radical anion. However, in the case of 1, the greater delocalization of the radical anion over the whole aromatic system led to a more complex hyperfine splitting pattern. The CVs of these two compounds are in agreement with their reduction tendency, as well as with the electron affinities associated with their LUMO energy level values. Thus, we can propose that the non-existence of isoaporphines (the corresponding 7-deoxo-1,2,3,4-tetrahydro analogues) in nature and the difficulty attending their synthetic preparation is due to the instability of the annelated 4-aminophenols generated in the reduction of oxoisoaporphine analogues, and the great capacity of the oxoisoaporphines to delocalize an unpaired electron.

ACKNOWLEDGMENTS

E.S.-S. thanks Fundación Andes for a scholarship and Vanessa Franchini B. for her unconditional support. This work was funded in part by FONDECYT Grant N° 2010056.

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