DFT calculations of pentalenoquinones: towards the interception of 2-bromopentalene-1,5-dione

This paper is dedicated to Professor Udo H. Brinker on the occasion of his 65 th birthday Abstract To reveal the stability and the aromatic character of pentalenoquinones (PQs) 1 - 4 and the corresponding bromo derivatives (Br-PQs) 6 - 9 , DFT calculations (B3LYP/6-311+G(d,p)) concerning the geometry optimization, total energy and nucleus independent chemical shift (NICS) values were performed. It was found that all of the compounds have planar geometry. As the energy difference between HOMO-LUMO energy levels ( ∆ε = ε LUMO – ε HOMO ) and total energies were considered for the pentalene family, the stability order was found to be 1 > 2 > 3 > 4 for PQs, and 6 > 7 > 8 > 9 for Br-PQs. Furthermore 2-bromopentalene-1,5-dione ( 6 ) in solution was investigated and noted that it was too reactive to be isolated or even trapped.


Introduction
Pentalenoquinones (PQs) 1-4, quinone derivatives of pentalene (5), may be defined as fully unsaturated derivatives of various isomeric bicyclo[3.3.0]octanediones and have fascinated scientists due to their extraordinary physical and chemical properties (Figure 1).For example, Delamere et al. have reported on the geometries, bond orders, chemical hardness, the NICS values and homodesmoric ring-opening reactions. 1Recently, Yavari and co-workers 2 reported the structural optimization of PQs with semi-empirical and ab initio calculations, providing a picture of geometries of PQs from both structural and energetic points of view; and 1,5-PQ, 1, was calculated to be the most stable isomer, albeit elusive.Although the chemistry of PQs, such as 1, has been the subject of some theoretical studies, the extent of our present understanding regarding the stability, Diels-Alder and the (non)aromatic character of 1 is meager due to the lack of an extensive theoretical study as well as experimental evidence which demonstrates the existence of free 1. 3 Herein we wish to report the results of our research in this field concerning DFT calculations geometry optimization, total energy and nucleus independent chemical shift (NICS) values 4 for the pentalene family, 1-10.Furthermore, the fate of 2-bromopentalene-1,5-dione (6) in solution was investigated.

Theoretical calculations
We first ran DFT calculations for compounds 1-5.Geometry optimizations were performed at the level of B3LYP/6-311+G(d,p) [5][6][7] to reveal at least a local minimum on the potential energy surface for each set of calculations, vibrational analyses were done (using the same basis set employed in the corresponding geometry optimizations).The normal mode analysis for each structure yielded no imaginary frequencies for the 3N−6 vibrational degrees of freedom, where N is the number of atoms in the system.This indicates that the structure of each molecule corresponds to at least a local minimum on the potential energy surface.Figure 2 shows the optimized structures for compounds 1-5 and bond lengths in Ǻ, respectively.For the optimized structures, HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energies (ε in eV), dipole moments (in Debye) and point groups were listed in Table 1.As the difference between HOMO-LUMO energy levels (∆ε = ε LUMO -ε HOMO ) was considered, the order was found to be 1 > 2 > 3 > 4 for PQs.

O O
In order to evaluate what effect a bromine atom would have on the energy profile of compounds 1-5, we performed DFT calculations at the same level for the corresponding bromo derivatives 6-10 (Fig. 3.).It was found that the presence of a bromine atom in the structure causes elongation or contraction of certain bonds (for example compare 1 and 6).When the difference between HOMO and LUMO energy levels (∆ε = ε LUMO -ε HOMO ) was considered, the order was found to be 6 > 7 > 8 > 9 for bromo-PQs.Furthermore, we noticed that the insertion of bromine atom decreased the energy gap (∆ε) between HOMO and LUMO.It is well established that Nucleus Independent Chemical Shift (NICS) is an indication of aromatic and/or anti-aromatic character for a given system. 4To get insight into the aromatic character of each member of the pentalene family, NICS values (in ppm) were calculated at B3LYP/6-311 G (d,p) level of theory based on the B3LYP/6-311 + G(d,p) optimized structures.NICS (0) calculations showed that there is no definite indication of aromatic and/or anti-aromatic character for PQs and Br-PQs.This result is consistent with previous findings in the literature. 1 However, it is worth noting that the bromine atom insertion generally decreased the NICS (0) values especially in the case of ring a.For example, on the one hand for pentalene, the NICS (0) value was decreased from 24.3 ppm to 21.1 ppm (compare 5 and 10 in Table 1), while on the other hand, for 3 and its bromo derivative 8, the NICS (0) value was increased from 6.5 ppm to 8.5 ppm (Table 1).These values were calculated relative to the most stable isomer 1. c These values were calculated relative to the most stable isomer 6.
To sum up the theoretical results, the lowest symmetry point group was found to be C s for the molecules and all of them have planar geometry.As the difference between HOMO-LUMO energy levels (∆ε = ε LUMO -ε HOMO ) was considered for the pentalene family 1-10, the order was found to be 1 > 6 > 2 > 7 > 3 > 8 > 5 > 4 > 10 > 9. Generally, the high energy gap value resulting from the relatively high energy of LUMO and low energy of HOMO indicates that neither losing nor capturing an electron will occur easily and, thus the compound is expected to be stable.Table 2 indicates some calculated energies of species at the B3LYP/6-311+G(d,p) level of theory.All the results showed that the stability order is 1 > 2 > 3 > 4 for PQs and 6 > 7 > 8 > 9 for Br-PQs.The calculated energy difference between the most favorable and unfavorable species is 64 and 69 kJ/mol for PQs and Br-PQs, respectively.In terms of total energy and enthalpy values, finding the stability order is similar to the stability order obtained in the case of frontier molecular orbital energy gaps.These theoretical results encouraged us to investigate the fate of 6 in solution, since it looks quite feasible among the others.

Scheme 1
In order to obtain the desired skeleton, we started with the known ketone 11. 8 Dibromo carbene addition to the double bond after protection of the carbonyl moiety with ethylene glycol in the presence of acid, provided 13 (Scheme 1) whose structure was elucidated on the basis of NMR spectral data.Careful inspection of the 1 H-NMR spectrum indicated the presence of two isomers (exo-and endo-) in a ratio of 3:1, respectively.The 1 H-NMR spectrum of exo-13 shows five sets of signals.The olefinic proton (H-6) appear as doublet at 5.93 ppm (J = 2.1 Hz) whereas the proton H-4 appears as a broad singlet at 4.62 ppm.The protons of the ring junction (H-3a and H-6a) give rise to multiplets between 3.50-3.00ppm.A ten-line (see below) 13 C-NMR spectrum is also in agreement with the structure.

Scheme 2
Interestingly, when compound 13 was treated with AgClO 4 in moist acetone, a mixture of hydroxy ketone 14 was the only isolated product and in 25% yield (Scheme 2).In an attempt to increase the yield of hydroxy ketone 14, we found that the reaction of 13 with NaOAc in HOAc provides compound 15 along with a minor product identified as 16 (Scheme 3).The 1 H-NMR spectrum of 16 indicated two olefinic protons resonate at 6.83 ppm (bs) and 5.79 (d, J = 1.8 Hz).The proton at the ring junction appears at 3.55 ppm as a triplet (J = 5.6 Hz), whereas the methylenic protons appear as two different AB systems between 3.00-2.00ppm.The 13  Treatment of 15 with K 2 CO 3 in CH 3 OH as the solvent followed by PCC oxidation of alcohol 14 in CH 2 Cl 2 , furnished the dione 17 in high yield (Scheme 3).In the 1 H-NMR spectrum of 17, the proton H-3 appears at 7.68 ppm (d, J = 3.0 Hz) as expected.However, the protons H-3a and H-6a resonate at 3.58 (m) and 3.17 (ddd, J = 11.9, 6.6 and 5.0 Hz).On the other hand, the methylenic protons give rise to two sets of AB systems between 2.80-2.00ppm. 9 Our initial exploratory efforts directed towards the dehydrogenation of 17 involved the use of selenoxide elimination. 10Disappointingly, the reaction did not proceed with 17 being recovered, unaltered.Dehydrogenation of 17 with dicyanodichloro-p-benzoquinone (DDQ) 11 in benzene for 12 h at ambient temperature indicated that ketone 17 was consumed but gave an insoluble polymeric material.Repeating the reaction either in the presence of furan or in benzene-d 6 under similar conditions gave the same results.This suggests, that 6 probably undergoes sequential intermolecular cycloaddition as soon as it is formed due to its high reactivity.

Conclusions
In summary, DFT calculations (B3LYP/6-311+G(d,p)) concerning the geometry optimization, total energy and nucleus independent chemical shift (NICS) values were performed in order to reveal the stability and aromatic character of PQs 1-4 and Br-PQs 6-9.It was found that all of them have planar geometry and if the difference between HOMO-LUMO energy levels (∆ε = ε LUMO -ε HOMO ) and total energies were considered, the stability order was found to be 1 > 2 > 3 > 4 for PQs, and 6 > 7 > 8 > 9 for Br-PQs.Furthermore, despite the quantum chemically indicated stability of PQ 6 when compared to other isomers, experimental results suggests that it is still too reactive to be isolated or even trapped in solution.

Experimental Section
General Procedures.Supplementary data concerning the details of the DFT calculations can be found in the online version via the internet.Geometry optimizations were performed at the level of B3LYP/6-311+G(d,p).The nucleus independent chemical shift (NICS) was used as a descriptor of aromaticity from the magnetic point of view.The index is defined as the negative value of the absolute magnetic shielding computed at ring centers or another interesting point of the system.In this study, NICS values were computed with GIAO B3LYP/6-311G (d,p) // B3LYP/6-311+G(d,p).NICS (0) was calculated at the geometrical center of the ring.For each set of calculations, vibrational analyses were done (using the same basis set employed in the corresponding geometry optimizations).The normal mode analysis for each structure yielded no imaginary frequencies for the 3N−6 vibrational degrees of freedom, where N is the number of atoms in the system.This indicates that the structure of each molecule corresponds to at least a local minimum on the potential energy surface.All the calculations for the geometry optimizations and energies were performed using Gaussian 98 program package and Spartan 06 package programme.Infrared spectra were recorded on a Mattson model 1000 FT-IR spectrometer. 1 H-and 13 C-NMR spectra were recorded on 400 and 100 MHz spectrometers (Brucker/Avance), respectively.Column chromatography was performed on silica gel (60-200 mesh) from Merck Company.TLC was carried out on Merck 0.2 mm silica gel 60 F254 analytical aluminum plates.All the solvent purification was done as stated in the literature. 12

Figure 2 .
Figure 2. The geometry optimized structures of compounds 1-5 and the bond lengths in Ǻ (a and b indicate the ring for NICS calculations).

Figure 3 .
Figure 3.The geometry optimized structures of compounds 6-10 and the bond lengths in Ǻ (a and b indicate the ring for NICS calculations).