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Article

Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine

by
Gabriela A. Corrêa
,
Susana L. H. Rebelo
* and
Baltazar de Castro
LAQV/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre s/n, 4169-007 Porto, Portugal
*
Author to whom correspondence should be addressed.
Molecules 2023, 28(9), 3940; https://doi.org/10.3390/molecules28093940
Submission received: 16 March 2023 / Revised: 22 April 2023 / Accepted: 5 May 2023 / Published: 7 May 2023
(This article belongs to the Special Issue Porphyrin-Based Compounds: Synthesis and Application)
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Abstract

:
Sustainable functionalization of renewable aromatics is a key step to supply our present needs for specialty chemicals and pursuing the transition to a circular, fossil-free economy. In the present work, three typically stable aromatic compounds, representative of products abundantly obtainable from biomass or recycling processes, were functionalized in one-pot oxidation reactions at room temperature, using H2O2 as a green oxidant and ethanol as a green solvent in the presence of a highly electron withdrawing iron porphyrin catalyst. The results show unusual initial epoxidation of the aromatic ring by the green catalytic system. The epoxides were isolated or evolved through rearrangement, ring opening by nucleophiles, and oxidation. Acridine was oxidized to mono- and di-oxides in the peripheral ring: 1:2-epoxy-1,2-dihydroacridine and anti-1:2,3:4-diepoxy-1,2,3,4-tetrahydroacridine, with TON of 285. o-Xylene was oxidized to 4-hydroxy-3,4-dimethylcyclohexa-2,5-dienone, an attractive building block for synthesis, and 3,4-dimethylphenol as an intermediate, with TON of 237. Quinoline was directly functionalized to 4-quinolone or 3-substituted-4-quinolones (3-ethoxy-4-quinolone or 3-hydroxy-4-quinolone) and corresponding hydroxy-tautomers, with TON of 61.

Graphical Abstract

1. Introduction

Biomimetic systems allow to reproduce enzyme activity while avoiding expensive enzyme extractions from natural sources and the expensive procedures of bio- and enzymatic catalysis. Iron and manganese porphyrins have shown the ability to mimic the remarkable activity of oxygenase enzymes, such as cytochrome P450, leading to efficient catalytic systems for sustainable oxidation of aromatic substrates, in mild conditions, and with novel reactivity patterns [1,2]. The porphyrin structure, the microenvironment, such as the solvent, co-catalyst, or catalyst support, have shown to play a key role on biomimetic efficiency [3,4].
A remarkable reaction of P450 during metabolism is the epoxidation of polycyclic aromatic compounds (PACs) in peripheral positions [5]. This reaction is not common in chemical systems, where PACs are mostly oxidized on the meso-rings to afford phenols, quinones, and analogues [6]. These are also observed using catalytic systems based on polyoxometalates [7], metallophthalocyanines [8], and metalloporphyrins [9].
In recent years, biomimetic aromatic epoxidations have been disclosed using Mn (2,6-dichlorophenyl)porphyrins (MnP) as catalysts (Scheme 1A–C), using non-green conditions, and epoxides of naphthalene, anthracene [10], tetracene [11], and acridine [12] have been obtained (Scheme 1A).
In some cases, epoxide formation was considered an intermediate step and products resulting from rearrangement of the epoxide ring were obtained, e.g., the o-diketone obtained in phenanthrene oxidation (Scheme 1B) [10,13]. It should be noted that alkylbenzenes oxidation in the presence of MnP catalytic systems afforded selectively alkyl group oxidation, e.g., toluene was oxidized mainly to benzoic acid and ethylbenzene to acetophenone (Scheme 1C) [14].
Interest in producing valued aromatic compounds from renewable sources has grown enormously in recent years, aiming to implement a circular economy and decrease dependence on fossil-based materials as feedstock in the fine chemicals industry [15,16,17].
Promising techniques for the production of platform green aromatics are the catalytic pyrolysis of biomass or wastes [18,19] and gas-phase Diels–Alder condensation of furan derivatives [20], among others. Optimization studies have been directed towards the increased production of the BTX (benzene, toluene, and xylenes) fraction, where xylenes are of major interest, for use as solvents and as intermediates for synthesis [21].
The chemical oxidation of o-xylene is described in the literature using harsh conditions, resulting in methyl groups functionalization [22], or degradation/removal from the environment [23]. Still, in biological systems, o-xylene is selectively oxidized in the aromatic ring by a diiron monooxygenase [24].
Quinoline and quinolone scaffolds are present in a vast number of natural compounds and pharmacologically active substances, comprising a significant segment of the pharmaceutical market [25]. Much has been achieved in developing greener syntheses of quinoline and its derivatives. In effect, quinoline can be obtained from biomass derivatives, such as glycerol or levulinic acid by reactions with aniline [26,27].
The direct oxidation of quinoline has been studied to obtain its degradation [28] or site-selective oxidation using enzymatic catalysis [29].
Acridine derivatives are also an important class of bioactive compounds with antibacterial and antimalarial activity and these have been studied as therapeutic agents for cancer and Alzheimer’s disease [12]. Acridine can be obtained from non-fossil sources by catalytic pyrolysis of amino acids [30]. Previous studies on biomimetic oxidation of acridine with Mn porphyrins led to direct and unprecedent epoxidation of the peripheral aromatic rings, disclosing the possibility of new functionalization routes (Scheme 1A) [12]. However, it would be desirable to obtain greener conditions, namely the substitution of acetonitrile as the solvent and improve product selectivity.
A green metalloporphyrin system for catalytic oxidation was described, using hydrogen peroxide as a green oxidant, producing water as the only byproduct, a highly electron withdrawing iron porphyrin [Fe(TPFPP)Cl] (FePF; Scheme 2), and ethanol as a green solvent, without any other additives or co-catalyst [FePF@H2O2_EtOH]. Moreover, improved methodologies for metalloporphyrin synthesis in eco-sustainable conditions have been reported [31]. This system has been effective in the epoxidation of alkenes and aromatic ring hydroxylation, but direct epoxidation of the aromatic ring has not been observed (Scheme 1D) [32,33].
The different catalytic activity of the MnPs and FePF has been ascribed to the formation of different active species in the catalytic cycle [3,14]. With the FePF, a hydroperoxyl species [PFe(III)-OOH] has been ascribed as the active oxidant, while an oxo-species is considered the active oxidant in the catalytic cycle of Mn porphyrins [PMn(V)=O] [32].
The present work describes the application of the [FePF@H2O2_EtOH] catalytic system, at room temperature (RT), in the oxidative valorization of the renewable aromatic compounds (Scheme 2).

2. Results and Discussion

The oxidation of o-xylene (1), quinoline (2), and acridine (3) was carried out by progressive addition of H2O2 at a rate of 0.6 mmol·h−1 in ethanol and at room temperature (RT), using the fluorinated iron porphyrin [Fe(TPFPP)Cl] (FePF) as catalyst. Control reactions performed in the absence of catalyst showed no substrate conversion during the catalytic reaction time.

2.1. o-Xylene (1)

The catalytic oxidation of o-xylene afforded two products, the 3,4-dimethylphenol (1a) and 4-hydroxy-3,4-dimethylcyclohexa-2,5-dienone (1b). The substrate conversion and product selectivity were monitored by GC-FID and the results are summarized in Table 1.
Using catalyst loadings of 0.3 and 0.6 mol %, the xylene conversion was 30% and 80%, respectively. These values are relevant in the context of C-H bond functionalization, where catalyst loadings between 2.5 and 15 mol % are commonly used [34]. The selectivity for the main product 1b is 86% and is independent of catalyst loading. The kinetic plot of the reaction described in entry 2 (Figure 1) shows a nearly constant yield of 1a during the reaction time, which indicates it as an intermediate of the final product 1b. The maximum conversion was reached after 2.5 h of reaction with a turnover number (TON) of 237.
Table
Table 1. Green oxidation of o-xylene by Fe porphyrin catalysis in ethanol at room temperature a.
Table 1. Green oxidation of o-xylene by Fe porphyrin catalysis in ethanol at room temperature a.
Molecules 28 03940 i001
Entry[FeP] (mol%)Time (min)Conversion (%) cSelectivity (%) cTON d
H2O2 (eq.) b1a1b
10.390
3 eq.		301486178
20.6150
5 eq.		801486237
a Reaction conditions: o-xylene (0,3 mmol), [Fe(TPFPP)Cl] (1–2 mg), ethanol (2 mL), H2O2 (5 mol eq.), at RT for 2.5 h; b H2O2 added at 2 mol equivalents/h; c Conversion and selectivity measured by GC-FID analysis; d Turnover number (TON), two catalytic cycles were considered for product 1b [35].
The MS spectrum obtained by GC-MS(EI) of the reaction mixtures are reported in Supplementary Material (SM). Compound 1a shows [M+●] m/z 122 and loss of CO and CH3 fragments as main peaks (Figure S1), matching 3,4-dimethylphenol [36]. The MS spectrum of 1b shows a di-oxygenated product with [M+●] m/z 138 (Figure S2). Compound 1b was isolated by fractionation of the reaction mixture using preparative thin layer chromatography (TLC) on silica gel and was fully characterized by 1H, 13C and 2D-NMR techniques.
The 1H NMR spectrum shows the two methyl groups at 1.46 and 2.09 ppm (Figure 2). The latter peak is a doublet with 4J = 1.5 Hz, due to a four-bonds coupling with H-2. The three signals in the alkene region corroborate the 4-hydroxycyclodienone structure. The H-2 signal is a quintet due long-range coupling with H-6 and CH3(C-3). A double doublet is ascribed to H-6 with 3J = 9.9 Hz and 4J = 2.0 Hz from coupling with adjacent H-5 and at four-bonds with H-2, respectively. These assignments are corroborated by the HMBC (1H^APT) spectrum (Figure 3) and by APT and HSQC spectra in SM (Figures S3 and S4).
To our knowledge, this compound has not been previously characterized or isolated and is an attractive building block for synthesis, e.g., as a dienophile in cycloaddition reactions or as a structural analogue of ring C of tetracycline family antibiotics [11]. The different chemoselectivity relative to the previously reported Mn porphyrin catalytic systems, which promote selective alkyl group oxidation [14], highlights this reaction as a new and completely green pathway for the selective functionalization of the aromatic ring of alkylbenzenes.

2.2. Quinoline (2)

The direct one-pot oxidation of quinoline afforded the quinolone products 3-ethoxy-4-quinolone (2a), 4-quinolone (2b) and 3-hydroxy-4-quinolone (2c). The latter two products were observed also as hydroxyquinoline tautomeric compounds: 4-hydroxyquinoline (2b*) and 3,4-dihydroxyquinoline (2c*). The results are collected in Table 2, where for simplicity, selectivity and yield for products 2b and 2c corresponds to joint values observed for tautomer compounds (2b and 2b*) or (2c and 2c*).
Quinoline consumption during the reaction was monitored by GC-FID, but reaction products were not observable by this technique. The reaction mixtures were fractionated by preparative TLC and all the collected fractions were analyzed by NMR and HR-ESI-MS2 to obtain products identification/characterization. Subsequently, product selectivity and substrate conversion were obtained by 1H NMR analysis of the final reaction mixtures in DMSO-d6. Similar values of substrate conversion were observed by both techniques for identical reaction conditions (Table 2, entries 1 and 2). Using catalyst loadings of 0.6 and 1.9 mol%, the substrate conversion was 57% and 70%, respectively, after 4 h of reaction time and upon addition of 8 mol equivalents of H2O2 (Table 2, entries 1 and 3).
The presence of a substituent at 3-position (ethoxy or hydroxy) was dependent on the work-up conditions, namely the temperature of solvent evaporation. Solvent evaporation at 60 °C in the rotary evaporator in Path I and at RT in Path II.
Upon Path I, the fractionation of the reaction mixture by preparative TLC, afforded the 3-ethoxyquinolin-4-(1H)-one (3-ethoxy-4-quinolone, 2a), which was isolated as the single reaction product (Table 2, entry 1).
The 1H NMR spectrum of 2a (Figure 4) shows the selective functionalization on the pyridyl ring, as the four signals in the aromatic region show a multiplicity and coupling pattern typical of a non-functionalized aromatic ring (COSY spectrum in SM, Figure S5). The two doublets at δ 4.01 ppm and 4.73 ppm (broad), coupling with each other (J = 4.8 Hz), are ascribed to H-2 and H-1(NH), respectively. The low δ values observed for H-2 and C-2 (HSQC spectrum in Figure 5) are expected for 3-substituted-4-quinolones [37], carrying an electron donor substituent at position 3. High electron density on C-2/H-2 is justified by the presence of mesomerism in compound 2a (Figure 4, upper insert), with a significant contribution of two zwitterionic resonance hybrids to describe its structure. This is confirmed by the multiplet signal at δ 3.91–4.00 ppm, ascribed to ethoxy -CH2 group. The contribution of the two zwitterionic structures leads to a hindrance in Ar-OEt bond rotation, resulting in distinct chemical environment on the -CH2 protons [38,39]. The hydroxyl tautomer of compound 2a, 3-ethoxy-4-hydroxyquinoline, was not observed.
We found no previous references in the literature for compound 2a, and this methodology may be an effective and green way to produce new 3-substituted quinolone derivatives, by direct functionalization of quinoline.
Upon Path II (solvent evaporation at RT, 17–22 °C), the fractionation of the reaction mixture by preparative TLC, afforded quinolin-4(1H)-one (4-quinolone, 2b) and 3-hydroxyquinolin-4(1H)-one (3-hydroxy-4-quinolone, 2c) and the corresponding tautomers 4-hydroxyquinoline (2b*) and 3,4-dihydroxyquinoline (2c*). The selectivity was 46% and 22% for the mixtures of tautomers (2b + 2b*) and (2c + 2c*), respectively (Table 2, entry 2).
Compounds 2b and 2b*, 2c and 2c* were identified by HR-ESI-MS2 (SM, Figures S7 and S8). The [M + H]+ ions in the MS spectra were m/z 146.060 and m/z 162.055 for compounds 2b/2b* and 2c/2c*, respectively. NMR studies in DMSO-d6 (1H, APT, COSY, and HSQC; SM, Figures S9 and S10) confirmed the identification of these compounds.
The 1H NMR spectrum of the total reaction, after evaporation at RT (Path II, Table 2, entry 2), was obtained in DMSO-d6 (SM, Figures S11 and S12). The area of chosen non-overlapping peaks from quinoline and reaction products were used for quantification of product selectivity, product yield and substrate conversion. The 4-hydroxy-tautomers were observed as the major products. It should be noted that the ferric center of [Fe(TPFPP)Cl] has a markedly acidic character [40] and may confers acidity to the reaction media, favoring the presence of hydroxyl-tautomers 2b* and 2c*.

2.3. Acridine (3)

Acridine oxidation yielded 1:2-epoxyacridine (3a) and anti-1:2,3:4-diepoxyacridine (3b). NMR studies of the reaction mixture after chromatographic separation of the catalyst allowed compounds’ identification by comparison with previously described data [12]. Better selectivity was obtained for compound 3a (90%, Table 1, entry 1) than in those studies using the MnP catalytic system (70%, Scheme 1) [12].
As acridine has an N atom in the structure, which confers basicity to the substrate that might influence the oxidation reaction, one reaction was carried out with addition of HNO3. The results are presented in Table 3. It is observed that the pH does not lead to significant changes in the conversion of acridine, resulting only in a small increase in the yield of the monoepoxide (3a).
According to the 1H spectrum of the reaction mixture, shown in Figure 6, there is a total of 18 protons, which indicates the presence of a mixture of the two products, 3a and 3b. The only two singlets present in the spectrum, at δ 8.38 and 8.20 ppm, correspond to H-9 of both compounds and their areas were used to quantify products selectivity. The 1H, APT, and COSY NMR spectra are reported in SM (Figures S13 and S14).

2.4. Catalyst Stability

The reactions were followed by UV–vis. At the beginning of the reaction, the Fe porphyrin Soret band, at 410 nm, is observed and its intensity decreases as the reaction proceeds. This indicates the concomitant oxidation of the porphyrin macrocycle (SM, Figures S15 and S16). The cessation of substrate conversion relates to the complete disappearance of the Soret band after the TON maximum of 237, 61, and 285 for o-xylene, quinoline, and acridine, respectively.

2.5. Considerations on the Mechanism

Catalytic performance of the [Fe(TPFPP)Cl] (FePF) might be associated with the typical acidic character of iron porphyrins [40], which is intensified by the strong electron-withdrawing porphyrin ligand due to extensive fluorination. The iron-hydroperoxy-species [PFe(III)-OOH] formed by coordination of hydrogen peroxide to the metal center and subsequent deprotonation, has been considered the active oxidant in the catalytic cycle. In the absence of a co-catalyst, it is not expected that this species evolve into an oxo species [32].
Metallo-hydroperoxy species have been described as the active oxidant in epoxidation reactions or in the generation hydroxyl radicals [3]. Previous studies showed that the Fe(III) porphyrin is effective in alkene epoxidation and aromatic hydroxylation and an EPR spin trap study confirmed the absence of free hydroxyl radicals in these conditions [3]. The [PFe-OOH] is a strong oxidant, which can be further activated in the presence of a protic solvent by hydrogen bond formation with the hydroperoxide group [41]. This leads to an enhanced δ+ at the distal oxygen (Scheme 3, central species).
In the present work, it was observed that, unlike Mn porphyrins in aprotic solvent (acetonitrile) and with a co-catalyst, the present [FePF@H2O2_EtOH] system performs the selective aromatic oxidation of o-xylene, the oxidation of the aza-ring of quinoline and the epoxidation of the peripheral ring of acridine.
In previous studies [31], it was pointed out that the action of this catalyst in the formation of naphthoquinone by naphthalene oxidation (Scheme 1D) can be explained by the formation of naphtol via an electrophilic substitution mechanism (Scheme 3A, path ii). The electrophilic attack of [Fe-OO(δ+)H] on the aromatic ring π-system, with formation of a carbocation intermediate and recovery of aromaticity by deprotonation of the adjacent proton.
However, the results of the present work suggest a direct epoxidation of the aromatic π-system (Scheme 3A, path i) by an addition reaction, and the hydroxylated derivatives formed result from subsequent rearrangement of the epoxide ring in acidic medium (path iii).
The presence of path (i) is confirmed by: (a) isolation of acridine epoxides; (b) formation of the quinoline derivatives 2a (3-ethoxy-4-quinolone) and 2c (3-hydroxy-4-quinolone) (Scheme 3C), either resulting by epoxide ring opening through nucleophilic attack of EtOH (60 °C) or H2O (RT); (c) regioselectivity of hydroxylation in the formation of the final xylene product 1b (Scheme 3B), suggesting epoxidation of the aromatic ring and not electrophilic substitution (path ii), as in the latter case, the derivatives should result from the formation of a tertiary carbocation intermediate, namely, 1,3-dihydroxy-4,5-dimethylbenzene or 3,4-dimethyl-o-benzoquinone.
The oxidation of intermediate I might occur also non-catalytically in the oxidizing reaction media, similarly to the formation of benzoquinones from hydroquinones previously observed [14].

3. Materials and Methods

3.1. Materials

The chloro [5,10,15,20-tetraquis(pentafluorophenyl)porphyrinate] iron (III) [Fe(TPFPP)Cl] (FePF) was prepared by a literature procedure, in environmentally compatible conditions, using microwave heating [31]. Quinoline (98%), acridine (97%), and H2O2 30% w/w were purchased from Sigma-Aldrich (St. Louis, MO, USA). o-Xylene (98%) n-hexane, and ethyl acetate were acquired from Fisher Scientific (Waltham, MA, USA). Ethanol was from AppliChem (Gatersleben, Germany). All solvents were p.a. grade. Nitric acid (65%) was from PanReac (Barcelona, Spain). The chromatographic purifications were carried out using silica gel 60 F254 from Merck (Darmstadt, Germany).

3.2. Instrumentation

The GC-FID analyses were performed using a Varian 3900 chromatograph (Palo Alto, CA, USA), using nitrogen as carrier, and GC-MS analyses were performed in a Thermo Scientific Trace 1300, coupled to a Thermo Scientific ISQ Single quadropole MS apparatus (Waltham, MA, USA), using helium as the carrier gas. In both cases, DB-5-type-fused silica Supelco (Sigma-Aldrich) capillary columns were used (30 m, 0.25 mm i.d.; 0.25 μm film thickness) and the temperature program was: 70 °C (1 min), 20 °C min−1 to 200 °C (5 min). The injector temperature was set at 200 °C and the detector temperature was set at 250 °C.
UV–vis absorption spectra were recorded at room temperature on a Genesys 10s Thermo Scientific Spectrophotometer in the region 300–800 nm.
High-resolution electrospray ionization mass spectra (HR-ESI-MS) were obtained using an LTQOrbitrap XL mass spectrometer (Thermo Scientific). Evaporated samples were dissolved in acetonitrile while reaction mixtures were directly injected and infused into the electrospray ion source at 10 μL·min−1. The spectrometer was operated in the positive ionization mode with the capillary voltage set to +3.1 kV, sheath gas flow to 6, and the temperature of the ion transfer capillary to 275 °C.
NMR spectra (1D and 2D) were recorded on Bruker Avance instruments operating at a frequency of 400 MHz for 1H experiments and 100 MHz for 13C experiments, with sample temperatures of 22 °C and using CDCl3 or DMSO-d6 as solvent (Euroisotop, Cambridge, UK).
NMR and MS analyses were performed at CEMUP (Centro de Materiais da Universidade do Porto).

3.3. Catalytic Oxidation Reactions

The catalytic experiments were performed using the following general procedure: The substrate (0.3 mmol), the catalyst [Fe(TPFPP)Cl] (FePF), from 0.3 mol % (1 mg, 1 μmol) to 1.9 mol% (5 mg, 5 μmol), as indicated in Table 1, Table 2 and Table 3, were dissolved in 2 mL of ethanol and stirred at RT (17–22 °C) protected from light. H2O2 (aq.) 30% w/w was progressively added to the reaction mixture, by addition of aliquots of 0.5 mol equivalents relatively to the substrate every 15 min. The reactions were terminated when the substrate conversion did not change despite the addition of H2O2. When specified, the acridine reaction media was acidified by addition of HNO3 until pH~4.6.
At the end of reactions, the solvent was evaporated at 60 °C in the rotary evaporator (Work-up-1, used for quinoline) or at RT (Work-Up 2, used for all substrates) and the reaction mixtures were separated by TLC, using mixtures of ethyl acetate: n-hexane as eluent: (40:60% v/v) for xylene (1) and (50:50% v/v) for quinoline (2) and acridine (3). Compounds were revealed on TLC plates using a UV lamp and were removed from silica with the same eluent used for chromatography.
For 1H NMR analyses of the total reaction mixtures, the final reaction was passed through a small plug of silica-gel and eluted with DMSO-d6.
Conversion (%) = [n (sum of products)/n of substrate]; Selectivity (%) = [n of product P/n (sum of products)]; Yield (%) = [n of product P/n of substrate].

3.4. Spectroscopic Data of Products

4-hydroxy-3,4-dimethylcyclohexa-2,5-dienone (1b) 1H NMR (CDCl3, 400 MHz) δ 1.46 (3H, s, CH3_C-4), 2.09 (3H, d, J = 1.5 Hz, CH3_C-3), 6.01 (1H, quintet, J = 1.5 Hz, H-2), 6.12 (1H, dd, J = 9.9, 2.0 Hz, H-6), 6.88 (1H, d, J = 9.9 Hz, H-5); 13C NMR (CDCl3, 400 MHz) δ 18.0 (CH3_C-3), 26.0 (CH3_C-4), 69.2 (C, C-4), 125.9 (CH, C-2), 127.0 (CH, C-6), 152.5 (CH, C-5), 161.7 (C, C-3), 185.8 (C, C-1); EIMS m/z (relative abundance %) 138 [M]+• (43), 123 (100), 110 (54), 95 (77).
3-ethoxy-4-quinolone (2a) 1H NMR (CDCl3, 400 MHz) δ 1.00 (3H, t, J = 7.1 Hz, -CH3), 3.96 (2H, m, -CH2), 4.01 (1H, d, J = 4.8 Hz, H-2), 4.73 (1H, d-broad, J = 4.8 Hz, H-1), 7.52 (1H, t, J = 8.2 Hz, H-6), 7.70 (1H, t, J = 8.0 Hz, H-7), 7.85 (1H, d, J = 8.0 Hz, H-8), 8.18 (1H, dd, J = 8.2, 1.3 Hz, H-5); 13C NMR (CDCl3, 400 MHz) δ 14.1 (-CH3), 54.6 (CH, C-2), 60.8 (-CH2), 124.6 (CH, C-5), 129.3 (CH, C-6), 130.1 (CH, C-8), 133.6 (CH, C-7).
4-quinolone (2b) 1H NMR (DMSO-d6, 400 MHz) δ 6.51 (1H, d, J = 9.0 Hz, H-3), 7.19 (1H, t, J = 7.8 Hz, H-6), 7.32 (1H, d, J = 7.9 Hz, H-8), 7.50 (1H, t, H-7), 7.66 (1H, d, J = 7.8 Hz, H-5), 7.91 (1H, d, J = 9.0 Hz, H-2); 13C NMR (DMSO-d6, 400 MHz) δ 115.6 (CH, C-8), 122.2 (CH, C-3), 122.3 (CH, C-6), 128.4 (CH, C-5), 130.9 (CH, C-7), 140.8 (CH, C-2), HRESIMS m/z (relative abundance %) 162.055 [M + H]+, (100), 144.045 (7), 134.060 (7), 116.050 (10).
4-hydroxyquinoline (2b*) 1H NMR (DMSO-d6, 400 MHz) δ 7.50 (1H, d, J = 7.3 Hz, H-3), 7.76 (1H, t, J = 7.5 Hz, H-6), 7.84 (1H, t, J = 8.4 Hz, H-7), 7.99 (1H, d, J = 7.3 Hz, H-2), 8.11 (1H, d, J = 7.5 Hz, H-5), 8.55 (1H, d, J = 8.4 Hz, H-8); 13C NMR (DMSO-d6, 400 MHz) δ 119.3 (CH, C-8), 122.4 (CH, C-3), 126.1 (CH, C-2), 129.1 (CH, C-5), 129.3 (CH, C-6), 130.9 (CH, C-7), 119.6 (C, C-4a), 141.2 (C, C-8a), 162.6 (C, C-4); HRESIMS m/z (relative abundance %) 146.060 [M + H]+, (100), 129.057 (2), 128.050 (3).

4. Conclusions

Inert aromatic compounds have been selectively functionalized by catalytic oxidation in mild and green conditions, using H2O2 as green oxidant, ethanol as green solvent, in the absence of other additives, at room temperature and using an electron withdrawing iron porphyrin catalyst, obtainable in eco-sustainable conditions, and used in a low loading of <2 mol%. The results support the occurrence of an initial direct epoxidation of the aromatic ring, leading to an unusual selectivity for o-xylene oxidation, as it occurred exclusively on the aromatic ring and not on the methyl groups, as previously observed. Moreover, the functionalization of acridine on the peripheral ring, instead of on the meso 9-position was unusual. The new methodology can be very attractive for the preparation of new 3-substituted quinolone derivatives, which have high potential for biological activity. The oxidations resulted in loss of aromaticity in products or in one of the aromatic rings. Two new compounds with attractive application potential were isolated and characterized.
The results point to the future relevance of aromatic epoxidation reactions, still largely unexplored in organic synthesis. This is mainly of importance in the valorization of aromatic products resulting from recycling processes based on pyrolysis of biomass and waste. Further developments of the catalytic system can be pursued developing more easily obtainable highly electron withdrawing iron catalysts.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/molecules28093940/s1, Figures S1 and S2: MS spectrum (EI) of products 1a and 1b; Figures S3 and S4: NMR spectra (APT and HSQC) of product 1b; Figures S5 and S6: NMR spectra (COSY and APT) of product 2a; Figures S7 and S8: HR-MS2 (ESI) spectra of products 2b and 2c; Figures S9 and S10: 2D-NMR spectra (COSY and HSQC) of a fraction containing compounds 2b, 2b* and 2c*; Figures S11 and S12: NMR spectra (1H and COSY) of a quinoline total reaction mixture; Figures S13 and S14: NMR spectra (COSY and APT) of a fraction containing compounds 3a and 3b; Figures S15 and S16: UV-vis of quinoline and acridine reaction mixtures.

Author Contributions

Conceptualization, S.L.H.R.; methodology, G.A.C. and S.L.H.R.; validation, G.A.C., S.L.H.R. and B.d.C.; investigation, G.A.C.; resources, S.L.H.R.; writing—original draft preparation, G.A.C. and S.L.H.R.; writing—review and editing, S.L.H.R. and B.d.C.; supervision, S.L.H.R. and B.d.C.; funding acquisition, B.d.C. All authors have read and agreed to the published version of the manuscript.

Funding

This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through the projects UIDB/50006/2020 and UIDP/50006/2020.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The work was supported through the projects UIDB/50006/2020 and UIDP/50006/2020, funded by FCT/MCTES through national funds. S.L.H.R. thanks FCT (Fundação para a Ciência e Tecnologia) for funding through program DL 57/2016—Norma transitória (Ref. REQUIMTE/EEC2018/30). The authors thank M. Graça P.M.S. Neves, from the University of Aveiro, for her contribution to compound 2a NMR spectra interpretation.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Huang, X.; Groves, J.T. Oxygen Activation and Radical Transformations in Heme Proteins and Metalloporphyrins. Chem. Rev. 2018, 118, 2491–2553. [Google Scholar] [CrossRef] [PubMed]
  2. Calvete, M.J.F.; Piñeiro, M.; Dias, L.D.; Pereira, M.M. Hydrogen Peroxide and Metalloporphyrins in Oxidation Catalysis: Old Dogs with Some New Tricks. ChemCatChem 2018, 10, 3615–3635. [Google Scholar] [CrossRef]
  3. Rebelo, S.L.H.; Moniz, T.; Medforth, C.J.; de Castro, B.; Rangel, M. EPR spin trapping studies of H2O2 activation in metaloporphyrin catalyzed oxygenation reactions: Insights on the biomimetic mechanism. Mol. Catal. 2019, 475, 110500. [Google Scholar] [CrossRef]
  4. Lipińska, M.E.; Rebelo, S.L.H.; Pereira, M.F.R.; Figueiredo, J.L.; Freire, C. Photoactive Zn(II)Porphyrin–multi-walled carbon nanotubes nanohybrids through covalent β-linkages. Mater. Chem. Phys. 2013, 143, 296–304. [Google Scholar] [CrossRef]
  5. Shimada, T.; Fujii-Kuriyama, Y. Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and 1B1. Cancer Sci. 2004, 95, 1–6. [Google Scholar] [CrossRef]
  6. Haynes, J.P.; Miller, K.E.; Majestic, B.J. Investigation into Photoinduced Auto-Oxidation of Polycyclic Aromatic Hydrocarbons Resulting in Brown Carbon Production. Environ. Sci. Technol. 2019, 53, 682–691. [Google Scholar] [CrossRef] [PubMed]
  7. Estrada, A.C.; Simões, M.M.Q.; Santos, I.C.M.S.; Neves, M.G.P.M.S.; Cavaleiro, J.A.S.; Cavaleiro, A.M.V. Oxidation of Polycyclic Aromatic Hydrocarbons with Hydrogen Peroxide in the Presence of Transition Metal Mono-Substituted Keggin-Type Polyoxometalates. ChemCatChem 2011, 3, 771–779. [Google Scholar] [CrossRef]
  8. Sorokin, A.; Meunier, B. Oxidation of Polycyclic Aromatic Hydrocarbons Catalyzed by Iron Tetrasulfophthalocyanine FePcS: Inverse Isotope Effects and Oxygen Labeling Studies. Eur. J. Inorg. Chem. 1998, 1998, 1269–1281. [Google Scholar] [CrossRef]
  9. Giri, N.G.; Chauhan, S.M.S. Oxidation of polycyclic aromatic hydrocarbons with hydrogen peroxide catalyzed by Iron(III)porphyrins. Catal. Commun. 2009, 10, 383–387. [Google Scholar] [CrossRef]
  10. Rebelo, S.L.H.; Simões, M.M.Q.; Neves, M.G.P.M.S.; Silva, A.M.S.; Cavaleiro, J.A.S. An efficient approach for aromatic epoxidation using hydrogen peroxide and Mn(iii) porphyrins. Chem. Commun. 2004, 5, 608–609. [Google Scholar] [CrossRef]
  11. Costa, P.; Linhares, M.; Rebelo, S.L.H.; Neves, M.G.P.M.S.; Freire, C. Direct access to polycyclic peripheral diepoxy-meso-quinone derivatives from acene catalytic oxidation. RSC Adv. 2013, 3, 5350–5353. [Google Scholar] [CrossRef]
  12. Linhares, M.; Rebelo, S.L.; Biernacki, K.; Magalhães, A.L.; Freire, C. Biomimetic one-pot route to acridine epoxides. J. Org. Chem. 2015, 80, 281–289. [Google Scholar] [CrossRef] [PubMed]
  13. Rebelo, S.L.H.; Pires, S.M.G.; Simões, M.M.Q.; de Castro, B.; Neves, M.G.P.M.S.; Medforth, C.J. Biomimetic Oxidation of Benzofurans with Hydrogen Peroxide Catalyzed by Mn(III) Porphyrins. Catalysts 2020, 10, 62. [Google Scholar] [CrossRef]
  14. Rebelo, S.L.H.; Simões, M.M.Q.; Neves, M.G.P.M.S.; Cavaleiro, J.A.S. Oxidation of alkylaromatics with hydrogen peroxide catalysed by manganese(III) porphyrins in the presence of ammonium acetate. J. Mol. Catal. A Chem. 2003, 201, 9–22. [Google Scholar] [CrossRef]
  15. Dutta, S.; Bhat, N.S.; Anchan, H.N. Nanocatalysis for Renewable Aromatics. In Heterogeneous Nanocatalysis for Energy and Environmental Sustainability; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2022; pp. 61–90. [Google Scholar]
  16. Wollensack, L.; Budzinski, K.; Backmann, J. Defossilization of pharmaceutical manufacturing. Curr. Opin. Green Sustain. Chem. 2022, 33, 100586. [Google Scholar] [CrossRef]
  17. Niziolek, A.M.; Onel, O.; Guzman, Y.A.; Floudas, C.A. Biomass-Based Production of Benzene, Toluene, and Xylenes via Methanol: Process Synthesis and Deterministic Global Optimization. Energy Fuels 2016, 30, 4970–4998. [Google Scholar] [CrossRef]
  18. Wang, S.; Li, Z.; Yi, W.; Fu, P.; Zhang, A.; Bai, X. Renewable aromatic hydrocarbons production from catalytic pyrolysis of lignin with Al-SBA-15 and HZSM-5: Synergistic effect and coke behaviour. Renew. Energy 2021, 163, 1673–1681. [Google Scholar] [CrossRef]
  19. Genuino, H.C.; Muizebelt, I.; Heeres, A.; Schenk, N.J.; Winkelman, J.G.M.; Heeres, H.J. An improved catalytic pyrolysis concept for renewable aromatics from biomass involving a recycling strategy for co-produced polycyclic aromatic hydrocarbons. Green Chem. 2019, 21, 3802–3806. [Google Scholar] [CrossRef]
  20. Gancedo, J.; Faba, L.; Ordóñez, S. From Biomass to Green Aromatics: Direct Upgrading of Furfural–Ethanol Mixtures. ACS Sustain. Chem. Eng. 2022, 10, 7752–7758. [Google Scholar] [CrossRef]
  21. Zeng, Y.; Wang, Y.; Liu, Y.; Dai, L.; Wu, Q.; Xia, M.; Zhang, S.; Ke, L.; Zou, R.; Ruan, R. Microwave catalytic co-pyrolysis of waste cooking oil and low-density polyethylene to produce monocyclic aromatic hydrocarbons: Effect of different catalysts and pyrolysis parameters. Sci. Total Environ. 2022, 809, 152182. [Google Scholar] [CrossRef]
  22. Wellmann, A.; Grazia, L.; Bermejo-Deval, R.; Sanchez-Sanchez, M.; Lercher, J.A. Effect of promoters on o-xylene oxidation pathways reveals nature of selective sites on TiO2 supported vanadia. J. Catal. 2022, 408, 330–338. [Google Scholar] [CrossRef]
  23. Mei, J.; Shen, Y.; Wang, Q.; Shen, Y.; Li, W.; Zhao, J.; Chen, J.; Zhang, S. Roles of Oxygen Species in Low-Temperature Catalytic o-Xylene Oxidation on MOF-Derived Bouquetlike CeO2. ACS Appl. Mater. Interfaces 2022, 14, 35694–35703. [Google Scholar] [CrossRef] [PubMed]
  24. Zhou, T.-P.; Deng, W.-H.; Wu, Y.; Liao, R.-Z. QM/MM Calculations Suggest Concerted O–O Bond Cleavage and Substrate Oxidation by Nonheme Diiron Toluene/o-Xylene Monooxygenase. Chem. Asian J. 2022, 17, e202200490. [Google Scholar] [CrossRef]
  25. Batista, V.F.; Pinto, D.C.G.A.; Silva, A.M.S. Synthesis of Quinolines: A Green Perspective. ACS Sustain. Chem. Eng. 2016, 4, 4064–4078. [Google Scholar] [CrossRef]
  26. Nasseri, M.A.; Zakerinasab, B.; Kamayestani, S. Proficient Procedure for Preparation of Quinoline Derivatives Catalyzed by NbCl5 in Glycerol as Green Solvent. J. Appl. Chem. 2015, 2015, 743094. [Google Scholar] [CrossRef]
  27. Ortiz-Cervantes, C.; Flores-Alamo, M.; García, J.J. Synthesis of pyrrolidones and quinolines from the known biomass feedstock levulinic acid and amines. Tetrahedron Lett. 2016, 57, 766–771. [Google Scholar] [CrossRef]
  28. Jiao, Z.; Zhang, X.; Gong, H.; He, D.; Yin, H.; Liu, Y.; Gao, X. CuO-doped Ce for catalytic wet peroxide oxidation degradation of quinoline wastewater under wide pH conditions. J. Ind. Eng. Chem. 2022, 105, 49–57. [Google Scholar] [CrossRef]
  29. Wang, Z.; Zhao, L.; Mou, X.; Chen, Y. Enzymatic approaches to site-selective oxidation of quinoline and derivatives. Org. Biomol. Chem. 2022, 20, 2580–2600. [Google Scholar] [CrossRef]
  30. Sharma, R.K.; Chan, W.G.; Hajaligol, M.R. Product compositions from pyrolysis of some aliphatic α-amino acids. J. Anal. Appl. Pyrolysis 2006, 75, 69–81. [Google Scholar] [CrossRef]
  31. Rebelo, S.L.; Silva, A.M.; Medforth, C.J.; Freire, C. Iron(III) Fluorinated Porphyrins: Greener Chemistry from Synthesis to Oxidative Catalysis Reactions. Molecules 2016, 21, 481. [Google Scholar] [CrossRef]
  32. Rebelo, S.L.H.; Pereira, M.M.; Simões, M.M.Q.; Neves, M.G.P.M.S.; Cavaleiro, J.A.S. Mechanistic studies on metalloporphyrin epoxidation reactions with hydrogen peroxide: Evidence for two active oxidative species. J. Catal. 2005, 234, 76–87. [Google Scholar] [CrossRef]
  33. Rebelo, S.L.H.; Pires, S.M.G.; Simões, M.M.Q.; Medforth, C.J.; Cavaleiro, J.A.S.; Neves, M.G.P.M.S. A Green and Versatile Route to Highly Functionalized Benzofuran Derivatives Using Biomimetic Oxygenation. ChemistrySelect 2018, 3, 1392–1403. [Google Scholar] [CrossRef]
  34. Dalton, T.; Faber, T.; Glorius, F. C–H Activation: Toward Sustainability and Applications. ACS Cent. Sci. 2021, 7, 245–261. [Google Scholar] [CrossRef] [PubMed]
  35. Kozuch, S.; Martin, J.M.L. “Turning Over” Definitions in Catalytic Cycles. ACS Catal. 2012, 2, 2787–2794. [Google Scholar] [CrossRef]
  36. Kurganova, E.A.; Frolov, A.S.; Koshel’, G.N.; Nesterova, T.N.; Shakun, V.A.; Mazurin, O.A. A Hydroperoxide Method for 3,4-Xylenol Synthesis. Pet. Chem. 2018, 58, 451–456. [Google Scholar] [CrossRef]
  37. Zalibera, Ľ.; Milata, V.; Ilavský, D. 1H and 13C NMR spectra of 3-substituted 4-quinolones. Magn. Reson. Chem. 1998, 36, 681–684. [Google Scholar] [CrossRef]
  38. Bergman, J.J.; Chandler, W.D. A Study of the Barriers to Rotation in Some Highly Substituted Diphenyl Ethers. Can. J. Chem. 1972, 50, 353–363. [Google Scholar] [CrossRef]
  39. Eddahmi, M.; Moura, N.M.M.; Bouissane, L.; Gamouh, A.; Faustino, M.A.F.; Cavaleiro, J.A.S.; Paz, F.A.A.; Mendes, R.F.; Lodeiro, C.; Santos, S.M.; et al. New nitroindazolylacetonitriles: Efficient synthetic access via vicarious nucleophilic substitution and tautomeric switching mediated by anions. New J. Chem. 2019, 43, 14355–14367. [Google Scholar] [CrossRef]
  40. Martins, M.B.M.S.; Corrêa, G.A.; Moniz, T.; Medforth, C.J.; de Castro, B.; Rebelo, S.L.H. Nanostructured binuclear Fe(III) and Mn(III) porphyrin materials: Tuning the mimics of catalase and peroxidase activity. J. Catal. 2023, 419, 125–136. [Google Scholar] [CrossRef]
  41. Rocha, M.; Rebelo, S.L.H.; Freire, C. Enantioselective arene epoxidation under mild conditions by Jacobsen catalyst: The role of protic solvent and co-catalyst in the activation of hydrogen peroxide. Appl. Catal. A Gen. 2013, 460–461, 116–123. [Google Scholar] [CrossRef]
Molecules 28 03940 sch001 550
Scheme 1. Main direct oxidations of aromatic compounds by biomimetic catalysis with (A–C) Mn porphyrin (MnP) and (D) Fe porphyrin (FePF).
Scheme 1. Main direct oxidations of aromatic compounds by biomimetic catalysis with (A–C) Mn porphyrin (MnP) and (D) Fe porphyrin (FePF).
Molecules 28 03940 sch001
Molecules 28 03940 sch002 550
Scheme 2. Biomimetic oxidation of renewable aromatics.
Scheme 2. Biomimetic oxidation of renewable aromatics.
Molecules 28 03940 sch002
Molecules 28 03940 g001 550
Figure 1. Kinetic curve of o-xylene catalytic oxidation reaction.
Figure 1. Kinetic curve of o-xylene catalytic oxidation reaction.
Molecules 28 03940 g001
Molecules 28 03940 g002 550
Figure 2. 1H NMR spectrum for product 1b in CDCl3 using tetramethylsilane (TMS) as reference.
Figure 2. 1H NMR spectrum for product 1b in CDCl3 using tetramethylsilane (TMS) as reference.
Molecules 28 03940 g002
Molecules 28 03940 g003 550
Figure 3. HMBC spectrum (1H^APT) for product 1b in CDCl3. Red circles mark key correlation signals.
Figure 3. HMBC spectrum (1H^APT) for product 1b in CDCl3. Red circles mark key correlation signals.
Molecules 28 03940 g003
Molecules 28 03940 g004 550
Figure 4. 1H NMR spectrum of product 2a in CDCl3 using tetramethylsilane (TMS) as reference.
Figure 4. 1H NMR spectrum of product 2a in CDCl3 using tetramethylsilane (TMS) as reference.
Molecules 28 03940 g004
Molecules 28 03940 g005 550
Figure 5. HSQC (1H^APT) spectrum from product 2a in CDCl3. Positive signals are in blue and negative signals are in red.
Figure 5. HSQC (1H^APT) spectrum from product 2a in CDCl3. Positive signals are in blue and negative signals are in red.
Molecules 28 03940 g005
Molecules 28 03940 g006 550
Figure 6. 1H NMR spectrum of products 3a and 3b from fraction (A2) in CDCl3 using tetramethylsilane (TMS) as reference.
Figure 6. 1H NMR spectrum of products 3a and 3b from fraction (A2) in CDCl3 using tetramethylsilane (TMS) as reference.
Molecules 28 03940 g006
Molecules 28 03940 sch003 550
Scheme 3. Mechanistic proposals.
Scheme 3. Mechanistic proposals.
Molecules 28 03940 sch003
Table
Table 2. Green oxidation of quinoline by Fe porphyrin catalysis in ethanol at room temperature a.
Table 2. Green oxidation of quinoline by Fe porphyrin catalysis in ethanol at room temperature a.
Molecules 28 03940 i002
Entry[FeP] (mol%)Conversion (%)Selectivity (Yield) (%)TON h
2a2b d2c dOther
10.957 e,f100 (57) g---61
21.353 f,g-46 (24) g22 (12) g27 (14) g-
31.970 e----38
a Reaction conditions: quinoline (0.3 mmol), [Fe(TPFPP)Cl] (3 mg), ethanol (2 mL), H2O2 (8 mol eq.), at RT for 4 h; b H2O2 added at 2 mol equivalents/h; c During the work-up, the evaporation of reaction mixture was performed in the rotavapor at 60 °C (I) or at RT (II); d For simplicity, this value corresponds to the joint selectivity of the two tautomer compounds observed; e Measured by GC-FID analysis; f Reaction mixture separated by TLC; g Measured by 1H NMR spectrum of the final reaction mixture; h Turnover number (TON).
Table
Table 3. Green oxidation of acridine by Fe porphyrin catalysis in ethanol at room temperature a.
Table 3. Green oxidation of acridine by Fe porphyrin catalysis in ethanol at room temperature a.
Molecules 28 03940 i003
Entry[FeP] (mol%)AdditiveConversion (%) cSelectivity (%) cTON d
3a3b
10.6None941090285
20.6HNO3
(pH 4.6)		891684261
a Reaction conditions: 2 mg of catalyst, 2 mL of solvent, 0.3 mmol of substrate, 5 eq. H2O2, 2h30 of reaction time; b H2O2 added at 2 mol equivalents/h; c Conversion and selectivity measured by 1H RMN; d Turnover number (TON), two catalytic cycles were considered for product 1b.
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Corrêa, G.A.; Rebelo, S.L.H.; de Castro, B. Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine. Molecules 2023, 28, 3940. https://doi.org/10.3390/molecules28093940

AMA Style

Corrêa GA, Rebelo SLH, de Castro B. Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine. Molecules. 2023; 28(9):3940. https://doi.org/10.3390/molecules28093940

Chicago/Turabian Style

Corrêa, Gabriela A., Susana L. H. Rebelo, and Baltazar de Castro. 2023. "Green Aromatic Epoxidation with an Iron Porphyrin Catalyst for One-Pot Functionalization of Renewable Xylene, Quinoline, and Acridine" Molecules 28, no. 9: 3940. https://doi.org/10.3390/molecules28093940

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