2. Results and Discussion
The initial experiments were performed with alcohols
1a–
3a and TAFF under microwave and infrared irradiation; the results are summarised in
Table 1. Thus, when compounds
1a–
3a were treated with TAFF/MW at 85 °C (100 W) until the disappearance of the starting material after 1.50 min, the corresponding cyclic trimers, namely cyclotripiperonylene (
1b, CTP, 85%), cyclotriveratrylene (
2b, CTV, 90%) and 1,2,3,6,7,8,11,12,13-nonamethoxy-10,15-dihydro-5
H-tribenzo[a,d,g]cyclononene (
3b, NDTC, 80%), were obtained (
Table 1, entries 1 and 3). These molecules are the condensation products of the corresponding benzylic cations. The cyclic trimers should proceed stepwise via the mono-, di- and trimeric cation species and should be followed by a closure step to give the compounds
1b–
3b [
3].
Table 1.
Synthesis of cyclovertrylenes a.
The reactions with alcohols
1a and
2a invariably produced a variety of other minor products, which could be a disproportionation product (
Table 1, compound
1c) or are a typical example of an acid-catalysed reaction of a primary alcohol to produce ethers (
Table 1, compounds
1d,
1e,
2c). The formation of
1f might be explained by a subsequent electrophilic aromatic substitution reaction between the ether
1e and the respective benzyl cation. In the case of alcohol
3a, 1,2,3,6,7,8,11,12,13-nonamethoxy-10,15-dihydro-5
H-tribenzo[a,d,g]cyclononene (
3b) was obtained as the major product, whereas the compounds
3c and
3d were the minor products. These products were formed (5% and 15%) as a consequence of the reaction conditions because, when the reaction was performed in carbon disulphide at reflux in the presence of TAFF for 7 h,
3b was obtained in lesser yield (7%) [
36,
37].
As shown in
Table 1, when the reactions of alcohols
1a–
3a were performed under infrared irradiation at 95 °C (375 W), similar results were obtained. The principle difference was the reaction time, which changed for each alcohol. Notwithstanding, a short irradiation time (3–7 min) was required for the complete disappearance of the starting material; this short time was ideal for our goal of developing a time-efficient process.
Next, we considered the possibility of using benzyl alcohols and testing the potential of TAFF/MW and TAFF/IR conditions for inducing the formation of benzyl oligomers. Thus, benzyl alcohol
4a yielded the oligomers
4c and
4d under MW conditions (Entry 1,
Table 2). When the reaction was performed using infrared irradiation, oligomers
4c–
e were formed (Entry 1,
Table 2). In the same context, we also investigated the reactivity of 2-methylbenzyl alcohol (
5a), which generated benzyl oligomers
5c–
f when the reaction was performed under MW conditions and benzyl ethers oligomers
5g–
i when the reaction was performed under infrared irradiation (Entry 2,
Table 2). Finally, 2-methoxybenzyl alcohol (
6a) yielded the benzyl oligomers
6c and
6d with both MW heating and infrared irradiation (Entry 3,
Table 2). In all cases, short irradiation times were necessary for complete reaction of the starting materials (4–10 min).
Table 2.
Synthesis of oligotoluenes using two different heating models: MW and IR a.
Given that it is not practical to purify the reaction mixtures by conventional chromatographic methods (CC or HPLC), the presence of these benzyl oligomers in the reaction mixtures was determined by the analysis of GC-EIMS and HRMS spectra following the protocol previously described by our group [
5,
6]. Thus, when the reaction was analysed by GC-EIMS, each spectrum showed a set of fragments that were assigned unequivocally to the molecular ion of each group of isomers. In addition, each molecular ion was confirmed using high-resolution experiments; consequently, the corresponding elemental composition was obtained (
Table 3). Notably, the respective elemental composition change was seven units for carbon and six units for hydrogen; this fact is in agreement with the difference of a benzyl moiety between the groups.
We next considered a theoretical analysis to rationalise the observed products and some of the key reaction steps in the oligomerisation reaction of benzyl alcohol
4a. We performed a detailed calculation of the molecular structure and electronic properties of the
ortho-,
meta- and
para-trimers, tetramers and pentamers (
Table 4) and predicted the relative reactivities and regioselectivities using density functional theory (or Conceptual DFT). We used DFT to analyse the chemical potential, electronegativity, hardness and condensed Fukui functions for an electrophilic aromatic substitution.
Table 3.
Elemental composition and high resolution data of oligotoluenes.
Table 4.
Structure of model compounds: dimer, trimer, tetramer and pentamer.
Thus, the geometry of the benzyl alcohol (
4a) (monomer) was determined using B3LYP/6-311G(d,p). The calculated results of the most stable conformation reproduced the bond distances, C-C
Ar, within 1.393–1.398 Å; this result is in agreement with the values previously reported for the same compound. Trætteberg and co-workers [
53] obtained a d(C-C
Ar) value of 1.394 Å using the gas electron diffraction method. This molecule has a conformational
gauche form with the OH group oriented toward the phenyl plane (not stable,
Figure 1(a)) and a
trans form with the OH group oriented away from the phenyl ring (not stable,
Figure 1(b)). When the hydrogen atoms on CH
2 are in
anti or
syn orientations to the hydrogen atom of the OH group, the energy difference between the two states is 0.36 kcal/mol. Additionally, the benzyl alcohol has both the
gauche (
Figure 1(c)) and
planar (
Figure 1(d)) orientations of the OH group, but with hydrogen atoms in semiperpendicular orientations toward the phenyl plane. The energy difference between the two states is 1.64 kcal/mol. Both conformational
gauche forms are stable, but the state with hydrogen atoms in a semiperpendicular orientation toward the phenyl plane is more stable, by 2.09 kcal/mol. The benzyl alcohol monomer in its stable form has dihedral angles CCCO = −32.2° and CCCOH = −58.0°.
Figure 1.
Conformers of benzyl alcohol.
Figure 1.
Conformers of benzyl alcohol.
The minimum energy molecules of the trimer, tetramer and pentamer can be substituted at the
ortho-,
meta- and
para-positions (
Table 4). These systems should exist as different isomers, with each isomer in its respective conformation. The substituted isomers display either a regular or irregular symmetry distribution. All of these structures are stable. The calculated energies of these isomeric compounds are shown in
Table 5. Of the three possible isomers of the trimer, the
meta-isomer appears to be the most stable, followed by the
para-isomers (the difference between the smallest and greatest is 1.19 kcal/mol). For the nine isomers of the tetramer,
meta-isomers are more stable than
para-isomers (the difference between the smallest and greatest is 3.56 kcal/mol). In the case of 39 isomers of the pentamer, the
meta substitution is more stable than
para-isomers (the difference between the smallest and greatest is 5.72 kcal/mol). The differences in the relative energies of the isomers of the trimers and tetramers are small and suggest that these isomers are almost identically stable. Additionally, a larger but still relatively small (given that they are conformers) difference in the energy is observed for the pentamers-isomer.
Table 5.
Computational details.
Table 5.
Computational details.
Structure | Ee (Hartrees) | Erel (Kcal/mol) | HOMO (eV) | LUMO (eV) | GAP (eV) | IP (eV) | EA (eV) | Χ (eV) | η (eV) | µ (eV) |
---|
4a | - | - | −6.81 | −0.40 | 6.41 | 8.68 | −1.66 | 3.60 | 5.26 | −3.60 |
4b | - | - | −6.54 | −0.40 | 6.14 | 8.18 | −1.17 | 3.51 | 4.67 | −3.51 |
4c-S1o | −773.166658 | 1.19 | −6.55 | −0.52 | 6.04 | 8.08 | −0.84 | 3.58 | 4.43 | −3.58 |
4c-S1m | −773.168557 | 0.00 | −6.44 | −0.46 | 5.98 | 7.83 | −0.87 | 3.48 | 4.35 | −3.48 |
4c-S1p | −773.168276 | 0.18 | −6.36 | −0.45 | 5.92 | 7.76 | −0.87 | 3.44 | 4.31 | −3.44 |
4d-S1oo | −1043.594698 | 2.68 | −6.50 | −0.54 | 5.96 | 7.78 | −0.68 | 3.55 | 4.23 | −3.55 |
4d-S1om | −1043.597379 | 0.99 | −6.46 | −0.50 | 5.96 | 7.73 | −0.73 | 3.86 | 3.87 | −3.86 |
4d-S1op | −1043.596796 | 1.36 | −6.37 | −0.52 | 5.86 | 7.68 | −0.66 | 3.51 | 4.17 | −3.51 |
4d-S1mm | −1043.598465 | 0.31 | −6.43 | −0.53 | 5.90 | 7.67 | −0.69 | 3.49 | 4.18 | −3.49 |
4d-S1mp | −1043.598569 | 0.25 | −6.37 | −0.50 | 5.87 | 7.62 | −0.73 | 3.44 | 4.18 | −3.44 |
4d-S1pp | −1043.598254 | 0.45 | −6.30 | −0.46 | 5.84 | 7.49 | −0.69 | 3.40 | 4.09 | −3.40 |
4d-S2om | −1043.593291 | 3.56 | −6.51 | −0.53 | 5.97 | 7.75 | −0.68 | 3.54 | 4.22 | −3.54 |
4d-S2op | −1043.596965 | 1.25 | −6.40 | −0.53 | 5.87 | 7.70 | −0.71 | 3.50 | 4.21 | −3.50 |
4d-S2mm | −1043.598963 | 0.00 | −6.42 | −0.49 | 5.94 | 7.69 | −0.74 | 3.47 | 4.22 | −3.47 |
4e-S1ooo | −1314.022344 | 4.36 | −6.47 | −0.55 | 5.92 | 7.64 | −0.58 | 3.53 | 4.11 | −3.53 |
4e-S1oom | −1314.024711 | 2.88 | −6.37 | −0.56 | 5.81 | 7.58 | −0.57 | 3.50 | 4.07 | −3.50 |
4e-S1oop | −1314.024876 | 2.78 | −6.38 | −0.56 | 5.82 | 7.56 | −0.56 | 3.50 | 4.06 | −3.50 |
4e-S1omo | −1314.024522 | 3.00 | −6.51 | −0.56 | 5.95 | 7.67 | −0.56 | 3.55 | 4.11 | −3.55 |
4e-S1omm | −1314.027076 | 1.40 | −6.44 | −0.56 | 5.88 | 7.60 | −0.62 | 3.49 | 4.11 | −3.49 |
4e-S1omp | −1314.027660 | 1.03 | −6.36 | −-0.53 | 5.83 | 7.53 | −0.57 | 3.48 | 4.05 | −3.48 |
4e-S1opo | −1314.024289 | 3.14 | −6.42 | −0.55 | 5.87 | 7.64 | −0.53 | 3.56 | 4.08 | −3.56 |
4e-S1opm | −1314.027017 | 1.43 | −6.35 | −0.55 | 5.80 | 7.56 | −0.55 | 3.50 | 4.05 | −3.50 |
4e-S1opp | −1314.026242 | 1.92 | −6.32 | −0.51 | 5.81 | 7.52 | −0.59 | 3.46 | 4.05 | −3.46 |
4e-S1mom | −1314.027453 | 1.16 | −6.35 | −0.54 | 5.81 | 7.55 | −0.58 | 3.48 | 4.07 | −3.48 |
4e-S1mop | −1314.027335 | 1.23 | −6.31 | −0.49 | 5.81 | 7.51 | −0.61 | 3.45 | 4.06 | −3.45 |
4e-S1mmm | −1314.028818 | 0.30 | −6.43 | −0.55 | 5.88 | 7.58 | −0.61 | 3.48 | 4.10 | −3.48 |
4e-S1mmp | −1314.029167 | 0.08 | −6.33 | −0.51 | 5.82 | 7.49 | −0.61 | 3.44 | 4.05 | −3.44 |
4e-S1mpm | −1314.028720 | 0.36 | −6.31 | −0.50 | 5.81 | 7.47 | −0.60 | 3.43 | 4.03 | −3.43 |
4e-S1mpp | −1314.028319 | 0.62 | −6.27 | −0.49 | 5.78 | 7.39 | −0.58 | 3.41 | 3.99 | −3.41 |
4e-S1pop | −1314.025814 | 2.19 | −6.38 | −0.52 | 5.86 | 7.48 | −0.56 | 3.46 | 4.02 | −3.46 |
4e-S1pmp | −1314.028888 | 0.26 | −6.29 | −0.47 | 5.82 | 7.43 | −0.65 | 3.39 | 4.04 | −3.39 |
4e-S1ppp | −1314.028174 | 0.71 | −6.23 | −0.47 | 5.76 | 7.34 | −0.59 | 3.37 | 3.96 | −3.37 |
4e-S2ooo | −1314.021068 | 5.17 | −6.47 | −0.56 | 5.91 | 7.63 | −0.58 | 3.52 | 4.11 | −3.52 |
4e-S2oom | −1314.023710 | 3.51 | −6.43 | −0.53 | 5.91 | 7.58 | −0.60 | 3.49 | 4.09 | −3.49 |
4e-S2oop | −1314.023301 | 3.76 | −6.35 | −0.54 | 5.81 | 7.53 | −0.55 | 3.49 | 4.04 | −3.49 |
4e-S2omo | −1314.024372 | 3.09 | −6.35 | −0.55 | 5.80 | 7.61 | −0.57 | 3.52 | 4.09 | −3.52 |
4e-S2omm | −1314.027225 | 1.30 | −6.34 | −0.52 | 5.83 | 7.54 | −0.60 | 3.47 | 4.07 | −3.47 |
4e-S2omp | −1314.027168 | 1.34 | −6.33 | −0.53 | 5.80 | 7.51 | −0.57 | 3.47 | 4.04 | −3.47 |
4e-S2moo | −1314.024830 | 2.81 | −6.32 | −0.55 | 5.77 | 7.55 | −0.56 | 3.50 | 4.05 | −3.50 |
4e-S2mom | −1314.027493 | 1.13 | −6.35 | −0.52 | 5.82 | 7.53 | −0.62 | 3.45 | 4.07 | −3.45 |
4e-S2mop | −1314.026932 | 1.49 | -6.33 | −0.54 | 5.79 | 7.48 | −0.57 | 4.46 | 4.03 | −3.46 |
4e-S2mmo | −1314.027206 | 1.31 | -6.35 | −0.53 | 5.82 | 7.52 | −0.60 | 3.46 | 4.06 | −3.46 |
4e-S2mmm | −1314.029301 | 0.00 | −6.40 | −0.56 | 5.84 | 7.59 | −0.59 | 3.50 | 4.09 | −3.50 |
4e-S2mmp | −1314.028956 | 0.22 | −6.31 | −0.51 | 5.81 | 7.50 | −0.62 | 3.44 | 4.06 | −3.44 |
4e-S2poo | −1314.024639 | 2.92 | −6.35 | −0.53 | 5.81 | 7.57 | −0.59 | 3.49 | 4.08 | −3.49 |
4e-Spom | −1314.027489 | 1.14 | −6.34 | −0.51 | 5.83 | 7.52 | −0.62 | 3.45 | 4.07 | −3.45 |
4e-S2pop | −1314.026941 | 1.48 | −6.33 | −0.54 | 5.79 | 7.50 | −0.56 | 3.47 | 4.03 | −3.47 |
4e-S3oom | −1314.020185 | 5.72 | −6.47 | −0.58 | 5.89 | 7.70 | −0.56 | 3.57 | 4.13 | −3.57 |
4e-S3omp | −1314.024768 | 2.84 | −6.35 | −0.60 | 5.75 | 7.59 | −0.53 | 3.53 | 4.06 | −3.53 |
4e-S3mmp | −1314.023392 | 3.71 | −6.37 | −0.58 | 5.78 | 7.57 | −0.55 | 3.51 | 4.06 | −3.51 |
4e-S4moo | −1314.020794 | 5.34 | −6.44 | −0.55 | 5.89 | 7.62 | −0.59 | 3.51 | 4.11 | −3.51 |
4e-S4mom | −1314.023562 | 3.60 | −6.44 | −0.52 | 5.92 | 7.61 | −0.60 | 3.50 | 4.10 | −3.50 |
4e-S4mop | −1314.023314 | 3.76 | −6.34 | −0.54 | 5.79 | 7.52 | −0.55 | 3.48 | 4.04 | −3.48 |
Atomic charge values of the dimer, trimer, tetramer and pentamer are depicted in
Figure 2. For a particular atom type, differences in its atomic charge can be roughly correlated to differences in its nucleophilic power. The general pattern displayed by NPA [
54,
55,
56,
57,
58,
59,
60,
61,
62,
63,
64,
65,
66,
67] atomic charges collected in
Figure 2 gives the carbon atom in the
ortho isomer a negative value of approximately −0.208 e, although in this position, steric effects will be present.
Table 5 shows the HOMO and LUMO energies and the interfrontier molecular orbital energy gaps, ∆E = E
LUMO − E
HOMO, for the considered isomers. The band gap energy values also provide an indication of the stability of a system. For large band gaps, a greater amount of excitation energy is needed to remove an electron from the valence band. From the difference between the smallest and greatest data to the band gap energy values, it is possible to see that the trimer isomers
4c shows a gap of 0.12 eV, the tetramer isomers
4d has a value of 0.13 eV, and the pentamer isomers
4e has a value of 0.2 eV. As evident from the results in
Table 5, the
ortho isomer has the highest HOMO/LUMO gap because of the reduced torsional potential and interaction between the substituted groups. When the substitutions are in the
meta and
para positions, the difference in the band gap energy increases with the number of rings; the gap energy is 0.06 eV for the trimer, 0.10 eV for the tetramer and 0.12 eV for the pentamer. Therefore, for an aromatic compound, the HOMO–LUMO gaps must be sufficiently large to prevent electron localisation. This observation is a theoretically correct answer according to the rules of aromaticity—the smaller the HOMO–LUMO band gap, the less aromatic the system. Thus, a linear molecule is a non-aromatic, non-ring structure. If the substitutions are in the
ortho- and
para- positions, the difference in the band gap values between them is 0.12 eV for the trimers and tetramers and 0.16 eV for pentamers. The B3LYP/6-311G(d,p)-calculated HOMO, LUMO and gap energies of the studied oligomers are shown in
Figure 3. The 4e-S3omp pentamer has the lowest band-gap energy among this group at 5.75 eV, which means that this molecule is the most reactive of all the structures (
Table 5).
Figure 4 shows the HOMO and LUMO contour molecular orbitals of the more stable oligomers.
Figure 2.
Optimised structures obtained at the B3LYP/6-311G(d,p) level.
Figure 2.
Optimised structures obtained at the B3LYP/6-311G(d,p) level.
Figure 3.
Sketch of B3LYP/6-311G(d,p) calculated energies HOMO, LUMO levels.
Figure 3.
Sketch of B3LYP/6-311G(d,p) calculated energies HOMO, LUMO levels.
Figure 4.
The highest occupied and lowest unoccupied molecular orbitals.
Figure 4.
The highest occupied and lowest unoccupied molecular orbitals.
The results of the calculations of the reactivity indices, ionisation potential (IP), electron affinity (EA), electronegativity (χ) (as the negative of the chemical potential, µ), chemical potential and hardness (η) for all molecules investigated in this work, as obtained with the B3LYP/6-311G(d,p) model, are presented in
Table 5. The ionisation potential of a stable molecule is always positive. An inspection of
Table 5 reveals that all molecules present a positive value of the ionisation potential (trimer 7.76–8.01 eV, tetramer 7.49–7.78 eV and pentamer 7.34–7.67 eV). Thus, this result is an indication of the stability of the set of molecules. All of the structures present a negative value for the electron affinity, which indicates that energy is released when a neutral species becomes an anion. The difference between the smallest and greatest energies are −0.84 to 0.87 eV for the trimer, −0.66 to −0.74 eV for the tetramer and −0.53 to −0.62 eV for the pentamer. The released energy decreased with an increase in the number of rings. The monomer has the greatest value of electron affinity, which indicates that the anion is more stable relative to the neutral system. The electronegativity shows how the electrons will flow from regions of high electronic density in a molecule to other sites of lower electronic density. As such, this value is an important index of reactivity for a given system. As evident from the results in
Table 5, the electronegativities are given in the following order: 3.6 eV (monomer) > 3.51 eV (dimer) ≈ 3.58–3.44 eV (trimer) ≈ 3.55–3.47 eV (tetramer) ≈ 3.53–3.48 (pentamer). These results indicate that the monomer is more prone to attract electrons during the interaction with another chemical compound. However, we note that the chemical potential of the oligomers derivatives is localised in the following intervals: trimers −3.44 to −3.58 eV, tetramers −3.40 to −3.86 eV and pentamers −3.37 to −3.56 eV. The smallest chemical potential corresponds to substitutions in either
ortho or
meta positions; this result clarifies that the flow of charge transfer is from the
para position to the electrophile during an electrophilic aromatic substitution process. The global hardness of the oligomers, given as the difference between the smallest and largest values, is 4.31–4.43 eV for the trimers, 3.87–4.23 eV for the tetramers and 3.96–4.11 eV for the pentamers.
According to the principle of maximum hardness, more reactive systems will show low hardness values, and less reactive systems will show high hardness values [
58]. Molecules arrange themselves to maximise hardness. A high value of chemical hardness indicates high kinetic stability and low reactivity, and, thus, this parameter was found to be a cardinal index for molecular structure, bonding and reactivity. When we consider that the stability of the species is directly related to its hardness, then the stability of the pentasubstituted isomers is lower compared to those of the tetrasubstituted and trisubstituted isomers. Among the trisubstituted, tetrasubstituted and pentasubstituted isomers, the
ortho isomer was generally found to be the hardest, and the
meta- and
para-isomers were the softest. Thus, the hardness measure indicates that the
meta- and
para-isomers are the most reactive positional isomers.
To complement the charge analysis and find the active sites of the molecules, we calculated the Fukui functions. The results of the calculations of the condensed Fukui functions, f
–, for the benzylic alcohol monomers and for some oligomers are presented in
Table 6. The benzylic alcohol is more active towards an electrophilic attack through atom Cp (carbon atom in
para-position). The same atom is inactive for a radical attack or a nucleophilic attack. The dimer has the same activity for either of the two attacks at its
para carbon atom. The oligomer increases the number of benzylic alcohol units, and its Fukui index decreases. For the other carbon atoms, f
− decreased. The charge and HOMO–LUMO molecular orbitals allow us to establish that the growth of the oligomer could occur through the
meta- position, whereas the Fukui indices indicate that the reactivity is at the
para-position. According to
Figure 5 and
Table 6,
para-carbon in oligomers is the most nucleophilic.
Table 6.
Fukui indexe, f-, for selected atom, carbon atom, substitution in para.
Table 6.
Fukui indexe, f-, for selected atom, carbon atom, substitution in para.
System | Atom a | f- |
---|
4a | Cp | 0.191 |
4b | Cp | 0.126 |
| Cp | 0.127 |
4c-S1p | Cp | 0.079 |
| Cp | 0.078 |
4c-S1m | Cp | 0.079 |
| Cp | 0.091 |
| Cp | 0.088 |
4c-S1o | Cp | 0.080 |
| Cp | 0.082 |
| Cp | 0.083 |
| Cp | 0.083 |
4d-S1pp | Cp | 0.059 |
| Cp | 0.058 |
4d-S2om | Cp | 0.051 |
| Cp | 0.056 |
| Cp | 0.065 |
4d-S1mp | Cp | 0.062 |
| Cp | 0.070 |
| Cp | 0.058 |
4d-S1op | Cp | 0.061 |
| Cp | 0.070 |
4e-S1ppp | Cp | 0.044 |
| Cp | 0.044 |
4e-S2mop | Cp | 0.050 |
| Cp | 0.056 |
4e-S2pop | Cp | 0.045 |
| Cp | 0.057 |
4e-S2omp | Cp | 0.046 |
| Cp | 0.051 |
4e-S2mpp | Cp | 0.045 |
| Cp | 0.054 |
| Cp | 0.050 |
4e-S1opp | Cp | 0.48 |
| Cp | 0.045 |
4e-S1pmp | Cp | 0.038 |
| Cp | 0.040 |
4e-S1pop | Cp | 0.054 |
| Cp | 0.049 |
Figure 5.
Optimised structures obtained at the B3LYP/6-311G(d,p) level.
Figure 5.
Optimised structures obtained at the B3LYP/6-311G(d,p) level.
Scheme 1.
Proposed reaction mechanism for the oligomerisation process.
Scheme 1.
Proposed reaction mechanism for the oligomerisation process.
Finally, from a mechanistic point of view, the catalytic action of TAFF should enhance the electrophilic character of the benzyl alcohol and facilitate the electrophilic aromatic substitution reaction that yields the dimer
4b, which is the key intermediate to understand the formation of oligomers
4c–
e. The interaction between TAFF and benzyl alcohol might be due to the protonated and unprotonated active sites that correspond to the acidic Lewis character of the clay (
Scheme 1).