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Article

Synthesis of Xanthones, Thioxanthones and Acridones by a Metal-Free Photocatalytic Oxidation Using Visible Light and Molecular Oxygen

by
Alejandro Torregrosa-Chinillach
and
Rafael Chinchilla
*
Department of Organic Chemistry, Faculty of Sciences, and Institute of Organic Synthesis (ISO), University of Alicante, Apdo. 99, 03080 Alicante, Spain
*
Author to whom correspondence should be addressed.
Molecules 2021, 26(4), 974; https://doi.org/10.3390/molecules26040974
Submission received: 30 December 2020 / Revised: 3 February 2021 / Accepted: 9 February 2021 / Published: 12 February 2021
(This article belongs to the Section Organic Chemistry)
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Versions Notes

Abstract

:
9H-Xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines can be easily oxidized to the corresponding xanthones, thioxanthones and acridones, respectively, by a simple photo-oxidation procedure carried out using molecular oxygen as oxidant under the irradiation of visible blue light and in the presence of riboflavin tetraacetate as a metal-free photocatalyst. The obtained yields are high or quantitative.

1. Introduction

In the last years, photocatalysis has emerged enormously as a powerful tool in synthetic organic chemistry when promoting electron transfer-involved chemical transformations [1,2,3,4,5]. In this context, the use of visible light results particularly attractive due to its lack of absorbance by organic compounds [6,7]. This reduces side reactions, frequently associated with classical photochemical reactions carried out with high energy UV light absorbed directly by the molecule. When less energetic and innocuous visible light is employed, the addition of catalytic amounts of a sensitizer as photocatalyst is required, but the reaction setup results simple and is not too different from that of typical thermal chemistry, except for the light source. Among the most frequent and successful transformations carried out under these conditions are photoredox reactions [8,9,10,11,12,13,14,15,16,17].
The visible light-induced photocatalytic oxidation of benzylic bonds [18,19], especially when the final oxidant is the cheap and environmentally friendly molecular oxygen [20,21], results in a convenient and direct technique to generate the corresponding carbonyl systems. This concept can be applied to the preparation of interesting structural compounds such as xanthones, thioxanthones and acridones by oxidation of benzylic C-H bonds of appropriate precursors. Thus, xanthones (9H-xanthen-9-ones) are interesting to prepare [22,23], as their structural motif is present in compounds showing a multitude of biological activities, including α-glucosidase inhibition, as well as anticancer, anti-Alzheimer and anti-inflammatory properties [24,25,26,27]. Besides, thioxanthones have also shown interesting antitumor activities [28]. Moreover, acridones [acridin-9(10H)-ones] are important moieties present in antiviral and antitumor agents [29,30,31].
Xanthone has been obtained by photocatalytic oxidation of the benzylic methylene position in 9H-xanthene. Thus, ruthenium complexes as catalysts have been used, the oxidant being oxygen [32] or iodate salts [33,34]. Iron complexes have also been employed as catalysts under aerobic conditions [35,36,37], as well as a copper complex [38] or copper(II) chloride [39]. All these procedures, although effective, employ a metal-containing catalyst, something not too environmentally desirable. Therefore, procedures involving metal-free conditions have been explored. Thus, functionalized carbon-dots have been employed as catalysts for the photo-oxidation of 9H-xanthene, using tert-butyl hydroperoxide as oxidant [40], as well as graphitic carbon nitride, oxygen being the oxidant in this case [41]. Xanthones have also been prepared by visible-light aerobic oxidation of different 9H-xanthenes, a reaction promoted by the combination of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), tert-butyl nitrite and acetic acid [42]. In addition, 9H-xanthene has been photo-oxidized to xanthone using 9-mesityl-10-methylacridinium tetrafluoroborate dye as catalyst and Selectfluor as oxidant [43]. Moreover, a flavin-derivative has been shown to photocatalyze this oxidation reaction under aerobic conditions, although in the presence of trifluoroacetic acid [44].
The photocatalytic oxidation of the methylene position in N-substituted 9,10-dihydroacridines (acridanes) leading to acridones has been less frequently explored. Thus, irradiation of N-methylacridane in the presence of a manganese complex and oxygen gave the corresponding N-methylacridone [45], a transformation which has also been carried out with air but using a ruthenium complex as photocatalyst [46]. In addition, the former combination of DDQ, tert-butyl nitrite and acetic acid has also been used for the visible light-induced oxidation of 9,10-dihydroacridines to acridones [42].
We report now a very simple and environmentally benign preparation of xanthones, thioxanthones and acridones carried out by irradiation of 9H-xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines, respectively, with visible blue light in the presence of oxygen and using a low-costing metal-free photocatalyst.

2. Results and Discussion

Different organic dyes 1–7 (Figure 1), employed previously in other photoredox reactions [13,47,48], were explored as photocatalysts in the model photo-oxidation of 9H-xanthene (9a) to xanthone (10a), under a molecular oxygen atmosphere (1 atm, balloon) and irradiation with visible blue light during 8 h (Table 1).
When fluorescein sodium salt (1) was used as photocatalyst (5 mol%) in acetonitrile as solvent, the desired oxidation product 10a was obtained, although in a low conversion (Table 1, entry 1). Moreover, the proton nuclear magnetic resonance (1H NMR) analysis of the reaction crude also revealed the presence of a small amount of bixanthene 11 as an undesirable coupling byproduct (H9 singlet at 4.18 ppm [49]) (Table 1, entry 1). Changing the photocatalyst to 2′,7′-dichlorofluorescein (2) increased noticeably the conversion to xanthone 10a, with no bixanthene 11 being observed (Table 1, entry 2). The conversion to xanthone 10a resulted furtherly increased to 74% using eosin Y sodium salt (3) as photocatalyst, although, again, the presence of the bixanthene byproduct 11 was detected (Table 1, entry 3). However, the reaction performed poorly when photocatalyzed by rose bengal sodium salt (4) (Table 1, entry 4), similarly to when methylene blue (5) was employed (Table 1, entry 5).
Riboflavin (6), also known as vitamin B2, is a cheap naturally occurring yellow compound, and hence it can absorb visible light with a maximum in the blue range, increasing its redox power upon excitation [50,51,52,53,54]. Riboflavin performed poorly under the former reaction conditions (Table 1, entry 6), but the use of riboflavin tetraacetate (7) as photocatalyst gave full conversion to the desired xanthone 10a, with no traces of bixanthene 11 being observed in 1H NMR (Table 1, entry 7). Perhaps the higher solubility of 7 in organic solvents plays a role in its activity compared to 6. Moreover, we also explored if a metal-containing photocatalyst could be used, employing the very known visible light-absorbing complex Ru(bpy)3Cl2 (bpy = 2,2′-bipyridyl) (8) (Figure 1) [12,55,56], although its performance resulted very poor under these conditions (Table 1, entry 8).
Then, we explored the use of other solvents using riboflavin tetraacetate (7) as the optimum photocatalyst. Thus, the use of N,N’-dimethylformamide (DMF) gave a similar mixture of xanthone 10a and the bixanthene byproduct 11 (Table 1, entry 9), whereas the use of methanol gave both compounds in lower conversions (Table 1, entry 10). In addition, when dichloromethane was used as solvent, a mixture of 10a and 11 was obtained (Table 1, entry 11), but, when another chlorinated solvent such as 1,2-dichloroethane was used, the starting xanthene 9a was fully converted to the oxidation product 10a (Table 1, entry 12). With these results in hand, we chose acetonitrile as the solvent, attempting to avoid the use of a chlorinated solvent.
We also carried out the reaction under air in an open flask using the best reaction conditions (7 as photocatalyst and MeCN as solvent), but a conversion of only 55% to 10a was achieved with a noticeable 24% conversion to bixanthene 11 (Table 1, entry 13). In addition, the reaction was carried out after just sparging molecular oxygen into the solution and closing the reaction flask, avoiding the use of the balloon, but a 73% conversion to 10a and 26% for 11 was detected (Table 1, entry 14). Moreover, the reaction was carried out in the absence of any light, giving almost no reaction (Table 1, entry 15). Finally, the oxidation was attempted in the absence of photocatalyst 7, with only 8% conversion to 10a being obtained (Table 1, entry 16). We also used a lower photocatalyst loading (2 mol%), but a remaining 22% of starting 9a was observed.
Once we found the most appropriate reaction conditions for the photo-oxidation reaction, we extended the procedure to other 9H-xanthenes and related systems, observing in all cases full conversion to the desired oxidated derivative (Figure 2). Thus, when the methyl- or methoxy-substituted 9H-xanthenes 9b and 9c were photo-oxidized, the corresponding xanthones 10b and 10c were obtained in high isolated yields (Figure 2). In addition, when 9H-xanthenes with substituents such as fluoro, chloro or bromo were employed in the reaction, the corresponding halogenated xanthones 10d, 10e and 10f, respectively, were also isolated in high yields (Figure 2). Moreover, benzocondensed 9H-xanthenes were also employed in the oxidation reaction, affording the corresponding xanthones 10g and 10h (Figure 2). Furthermore, 9H-thioxanthene was also explored for the photo-oxidation reaction, affording quantitatively the final thioxanthone 10i (Figure 2).
We also used this photo-oxidation reaction with N-substituted 9,10-dihydroacridines (acridanes), obtaining excellent results of the corresponding acridones (Figure 2). Thus, when N-methyl-9,10-dihydroacridine was employed, acridone 10j was isolated in a 91% yield, whereas N-phenyl-9,10-dihydroacridine afforded the oxidation derivative 10k in 93% yield. In addition, the presence of different substituents on the N-phenyl ring in the last acridane, such as methyl, methoxy or fluoro, allowed isolating the corresponding acridones 10l, 10m and 10n, respectively, in high yields. Moreover, when a benzoyl N-substituent was present in the starting 9,10-dihydroacridine, the N-benzoylated acridone 10o was isolated in 82% yield. Furthermore, the presence of an acid-sensitive N-substituent, such as the tert-butoxycarbonyl (Boc) group was tolerated under these neutral oxidation conditions, allowing to isolate the N-Boc-acridone 10p in 89% yield.
This photo-oxidation reaction probably takes place similarly to other proposed aerobic photocatalytic oxidation of benzylic systems [57], although particularized to the use of riboflavin as photocatalyst [44]. Thus, it is known that the riboflavin nucleus is excited in the presence of visible light [50,51,52,53,54] and then would be able to oxidize the benzyl system to a cation radical, generating a riboflavin radical anion after a single-electron transfer (SET) process. This riboflavin radical anion can convert oxygen to a superoxide radical anion which reduces the benzyl cation radical to a benzyl radical able to react with oxygen to generate a benzyl hydroperoxide which would decompose to the carbonyl system. Singlet oxygen is probably involved in this process, as it is known that it can be produced by flavin sensitization [58].
We also explored this photo-oxidation reaction using the simple N-unsubstituted 9,10-dihydroacridine 9q as starting material, but, instead of the corresponding N-unsubstituted acridone, fully aromatized acridine (12) was isolated after 8 h in a 96% yield (Scheme 1). This photocatalytic oxidative dehydrogenation of acridine has been reported previously [42] and used as a procedure for the aromatization of N-heterocycles [59,60].

3. Materials and Methods

3.1. General Information

All reagents and solvents employed were of the best grade available and were used without further purification. Riboflavin tetraacetate (7) was obtained by acetylation of riboflavin (6) as described [61]. Substituted 9H-xanthenes 9b–h were prepared as reported [62]. Starting dihydroacridines 9j [63], 9k–n [64], 9o [65] and 9p [66] were obtained by N-substitution of 9,10-dihydroacridine (9q) following literature procedures. 9,10-Dihydroacridine (9q) was prepared by reduction of acridine as described [67]. The 1H and 13C spectra were recorded at room temperature on a Bruker Oxford AV300 at 300 MHz and 75 MHz, on a Bruker Oxford AV400 at 400 MHz and 101 MHz, or a Bruker Avance DRX500 at 500 MHz and 125 MHz, respectively (Bruker, Billerica, MA, USA), using CDCl3 as solvent and TMS as the internal standard. Reactions were carried out in borosilicate vials (length: 4 cm, diameter: 1.4 cm, volume: 4 mL) and irradiated in a EvoluchemTM PhotoRedOx Box Duo (HepatoChem Inc., Beverly, MA, USA) equipped with two EvoluchemTM CREE XPE 450–455 nm 18W LEDs (HCK1012-01-002) (HepatoChem Inc., Beverly, MA, USA).

3.2. General Procedure for the Photocatalytic Oxidation Reaction.

A mixture of 9 (0.2 mmol) and 7 (0.01 mmol, 5.4 mg) was dissolved in acetonitrile (0.4 mL), and the solution was bubbled with O2 for 2 min. The flask was closed and stirred at room temperature under an O2 atmosphere (balloon) with irradiation by blue LEDs during the indicated reaction time (Figure 2). After that, H2O (2 mL) was added, and the reaction product was extracted with AcOEt (3 × 2 mL). The combined organic phases were dried over MgSO4, filtered and evaporated under reduced pressure (15 Torr) to get the crude product, which was purified by flash column chromatography on silica gel (n-hexane/AcOEt gradients). The adducts 10 and 12 were identified by comparison of their NMR data with those of the literature (Supplementary Materials, NMR spectra).
9H-Xanthen-9-one (10a) [68]. White solid (39 mg, 99%); 1H NMR (400 MHz): δH = 8.34 (dd, J = 8.0, 1.5 Hz, 2H), 7.76–7.67 (m, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.41–7.33 (m, 2H) ppm; 13C NMR (101 MHz): δC = 177.3, 156.3, 134.9, 126.8, 124.0, 122.0, 118.1 ppm.
2-Methyl-9H-xanthen-9-one (10b) [68]. White solid (41 mg, 97%); 1H NMR (300 MHz): δH = 8.34 (dd, J = 8.0, 1.7 Hz, 1H), 8.16–8.08 (m, 1H), 7.75–7.66 (m, 1H), 7.56–7.44 (m, 2H), 7.42–7.32 (m, 2H), 2.47 (s, 3H) ppm; 13C NMR (101 MHz): δC = 177.4, 156.3, 154.5, 136.2, 134.7, 133.8, 126.8, 126.1, 123.8, 121.9, 121.6, 118.1, 117.9, 21.0 ppm.
2-Methoxy-9H-xanthen-9-one (10c) [68]. White solid (43 mg, 96%); 1H NMR (300 MHz): δH = 8.35 (dd, J = 8.0, 1.6 Hz, 1H), 7.76–7.67 (m, 2H), 7.52–7.29 (m, 4H), 3.92 (s, 3H) ppm; 13C NMR (75 MHz): δC = 177.2, 156.2, 156.1, 151.1, 134.7, 126.8, 125.0, 123.8, 122.2, 121.4, 119.5, 118.1, 105.9, 56.1 ppm.
2-Fluoro-9H-xanthen-9-one (10d) [68]. White solid (40 mg, 93%); 1H NMR (300 MHz): δH = 8.33 (dd, J = 8.0, 1.6 Hz, 1H), 8.02–7.93 (m, 1H), 7.80–7.70 (m, 1H), 7.55–7.35 (m, 4H) ppm; 13C NMR (101 MHz): δC = 176.7 (d, J = 2.2 Hz), 158.9 (d, J = 245.3 Hz), 156.3, 152.5 (d, J = 1.6 Hz), 135.2, 126.8, 124.3, 123.1 (d, J = 25.3 Hz), 122.8 (d, J = 7.1 Hz), 121.2, 120.1 (d, J = 7.8 Hz), 118.1, 111.6 (d, J = 23.5 Hz) ppm.
2-Chloro-9H-xanthen-9-one (10e) [69]. White solid (43 mg, 94%); 1H NMR (300 MHz): δH = 8.40–8.23 (m, 2H), 7.81–7.61 (m, 2H), 7.55–7.33 (m, 3H) ppm; 13C NMR (75 MHz): δC = 176.3, 156.2, 154.6, 135.3, 135.1, 129.9, 126.9, 126.2, 124.4, 122.8, 121.6, 119.9, 118.2 ppm.
2-Bromo-9H-xanthen-9-one (10f) [68]. White solid (52 mg, 94%); 1H NMR (400 MHz): δH = 8.45–8.41 (m, 1H), 8.31 (dd, J = 8.0, 1.8 Hz, 1H), 7.82–7.70 (m, 2H), 7.51–7.45 (m, 1H), 7.43–7.35 (m, 2H) ppm; 13C NMR (101 MHz): δC = 176.1, 156.1, 155.0, 137.8, 135.3, 129.3, 126.9, 124.4, 123.2, 121.6, 120.1, 118.2, 117.2 ppm.
7H-Benzo[c]xanthen-7-one (10g) [68]. White solid (42 mg, 85%); 1H NMR (300 MHz): δH = 8.70–8.63 (m, 1H), 8.44–8.37 (m, 1H), 8.27 (d, J = 8.7 Hz, 1H), 7.95–7.89 (m, 1H), 7.81–7.64 (m, 5H), 7.48–7.41 (m, 1H) ppm; 13C NMR (101 MHz): δC = 177.0, 155.9, 153.8, 136.7, 134.5, 129.7, 128.2, 127.0, 126.7, 124.6, 124.2, 124.2, 123.0, 122.6, 121.6, 118.2, 117.7 ppm.
9-Methyl-7H-benzo[c]xanthen-7-one (10h) [70]. White solid (45 mg, 86%); 1H NMR (300 MHz): δH = 8.68–8.60 (m, 1H), 8.26 (d, J = 8.8 Hz, 1H), 8.19–8.14 (m, 1H), 7.95–7.87 (m, 1H), 7.75–7.64 (m, 3H), 7.56 (d, J = 1.3 Hz, 2H), 2.49 (s, 3H) ppm; 13C NMR (101 MHz): δC = 177.1, 154.1, 153.8, 136.6, 135.7, 134.4, 129.6, 128.2, 126.9, 126.0, 124.3, 123.9, 123.0, 122.2, 121.7, 117.9, 117.7, 21.1 ppm.
9H-Thioxanthen-9-one (10i) [68]. White solid (42 mg, 99%); 1H NMR (300 MHz): δH = 8.63 (ddd, J = 8.1, 1.5, 0.6 Hz, 2H), 7.67–7.56 (m, 4H), 7.53–7.46 (m, 2H) ppm; 13C NMR (101 MHz): δC = 180.1, 137.4, 132.4, 130.0, 129.4, 126.5, 126.1 ppm.
10-Methylacridin-9(10H)-one (10j) [68]. Yellow solid (38 mg, 91%); 1H NMR (300 MHz): δH = 8.55 (dd, J = 8.0, 1.6 Hz, 2H), 7.75–7.65 (m, 2H), 7.53–7.46 (m, 2H), 7.31–7.24 (m, 2H), 3.87 (s, 3H) ppm; 13C NMR (101 MHz): δC = 178.1, 142.7, 134.1, 128.0, 122.5, 121.5, 114.9, 33.9 ppm.
10-Phenylacridin-9(10H)-one (10k) [71]. Yellow solid (50 mg, 93%); 1H NMR (500 MHz): δH = 8.60 (dd, J = 8.0, 1.6 Hz, 2H), 7.74–7.69 (m, 2H), 7.68–7.64 (m, 1H), 7.53–7.48 (m, 2H), 7.40–7.36 (m, 2H), 7.31–7.27 (m, 2H), 6.76 (d, J = 8.6 Hz, 2H) ppm; 13C NMR (125 MHz): δC = 178.3, 143.3, 139.1, 133.4, 131.2, 130.2, 129.8, 127.4, 121.9, 121.7, 116.9 ppm.
10-(p-Tolyl) acridin-9(10H)-one (10l) [71]. Yellow solid (53 mg, 94%); 1H NMR (500 MHz): δH = 8.59 (dd, J = 8.0, 1.5 Hz, 2H), 7.52–7.47 (m, 4H), 7.29–7.23 (m, 4H), 6.80 (d, J = 8.6 Hz, 2H), 2.54 (s, 3H) ppm; 13C NMR (125 MHz): δC = 178.3, 143.5, 139.8, 136.5, 133.3, 131.8, 129.9, 127.4, 122.0, 121.6, 117.0, 21.5 ppm.
10-(4-Methoxyphenyl) acridin-9(10H)-one (10m) [71]. Yellow solid (57 mg, 95%); 1H NMR (300 MHz): δH = 8.58 (dd, J = 8.1, 1.4 Hz, 2H), 7.55–7.46 (m, 2H), 7.31–7.24 (m, 4H), 7.22–7.16 (m, 2H), 6.82 (d, J = 8.6 Hz, 2H), 3.95 (s, 3H) ppm; 13C NMR (125 MHz): δC = 178.3, 160.3, 143.7, 133.4, 131.6, 131.2, 127.4, 122.1, 121.6, 117.0, 116.3, 55.8 ppm.
10-(4-Fluorophenyl) acridin-9(10H)-one (10n) [71]. Yellow solid (52 mg, 91%); 1H NMR (300 MHz): δH = 8.59 (dd, J = 8.0, 1.7 Hz, 2H), 7.56–7.48 (m, 2H), 7.45–7.34 (m, 4H), 7.33–7.26 (m, 2H), 6.75 (d, J = 8.4 Hz, 2H) ppm; 13C NMR (101 MHz): δC = 178.3, 163.0 (d, J = 250.4 Hz), 143.3, 135.0 (d, J = 3.4 Hz), 133.6, 132.1 (d, J = 8.7 Hz), 127.6, 122.0, 121.9, 118.4 (d, J = 22.8 Hz), 116.7 ppm.
10-Benzoylacridin-9(10H)-one (10o) [65]. Yellow solid (49 mg, 82%); 1H NMR (500 MHz): δH = 8.57 (dd, J = 8.1, 1.3 Hz, 2H), 7.85–7.80 (m, 2H), 7.69–7.63 (m, 1H), 7.58–7.53 (m, 2H), 7.48–7.43 (m, 2H), 7.36–7.31 (m, 2H), 7.19 (d, J = 8.5 Hz, 2H) ppm; 13C NMR (101 MHz): δC = 178.2, 172.7, 139.9, 135.7, 133.9, 132.4, 131.5, 129.8, 127.9, 122.9, 121.7, 116.6 ppm.
Tert-butyl 9-oxoacridine-10(9H)-carboxylate (10p) [66]. Yellow solid (52 mg, 89%); 1H NMR (300 MHz): δH = 8.48–8.41 (m, 2H), 7.71–7.63 (m, 2H), 7.61–7.55 (m, 2H), 7.39–7.31 (m, 2H), 1.69 (s, 9H) ppm; 13C NMR (75 MHz): δC = 178.7, 152.0, 139.6, 133.5, 127.4, 123.4, 123.0, 117.7, 86.4, 27.9 ppm.
Acridine (12) [72]. Yellow solid (34 mg, 96%); 1H NMR (300 MHz): δH = 8.76 (s, 1H), 8.27 (d, J = 8.8 Hz, 2H), 7.99 (d, J = 8.5 Hz, 2H), 7.83–7.74 (m, 2H), 7.57–7.49 (m, 2H) ppm; 13C NMR (101 MHz): δC = 148.3, 137.2, 131.1, 128.7, 128.4, 126.6, 126.1 ppm.

4. Conclusions

Riboflavin tetraacetate acts as a convenient photocatalyst in the visible light-promoted benzylic oxidation of 9H-xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines to xanthones, thioxanthones and acridones, respectively, using molecular oxygen as the oxidant in acetonitrile as solvent. This easy oxidation procedure allows the isolation of these interesting products in high to quantitative yields, using a methodology that avoids the use of metal-containing catalysts or chemical oxidants and working under neutral conditions.

Supplementary Materials

The following are available online, Figures S1–S34 NMR spectra, Figure S35 spectrum of the LED lamp, and Figures S36–S43 UV–visible absorption spectra of the photocatalysts.

Author Contributions

Conceptualization, methodology, project administration, supervision and writing original draft, R.C.; and investigation and methodology, A.T.-C. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the Spanish Ministerio de Economía, Industria y Competitividad (PGC2018-096616-B-I00 and CTQ201788171-P) and the University of Alicante (VIGROB-173).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in insert article or supplementary material here.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds 10a–j and 10m–p are available from the authors.

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Molecules 26 00974 g001 550
Figure 1. Photocatalysts employed in this study.
Figure 1. Photocatalysts employed in this study.
Molecules 26 00974 g001
Molecules 26 00974 g002 550
Figure 2. Photocatalyzed oxidation of 9H-xanthenes, 9H-thioxanthene and 9,10-dihydroacridines. Reaction time and yield, after isolation by flash chromatography, detailed for each compound.
Figure 2. Photocatalyzed oxidation of 9H-xanthenes, 9H-thioxanthene and 9,10-dihydroacridines. Reaction time and yield, after isolation by flash chromatography, detailed for each compound.
Molecules 26 00974 g002
Molecules 26 00974 sch001 550
Scheme 1. Photo-oxidation of 9,10-dihydroacridine.
Scheme 1. Photo-oxidation of 9,10-dihydroacridine.
Molecules 26 00974 sch001
Table
Table 1. Screening and optimization of the reaction conditions for the photo-oxidation of 9H-xanthene.
Table 1. Screening and optimization of the reaction conditions for the photo-oxidation of 9H-xanthene.
Molecules 26 00974 i001
EntryPhotocatalyst Solvent10a Conversion (%) a11 Conversion (%) a
11MeCN134
22MeCN650
33MeCN7415
44MeCN72
55MeCN100
66MeCN113
77MeCN1000
88MeCN60
97DMF4753
107MeOH3113
117CH2Cl25644
127ClCH2CH2Cl1000
13 b7MeCN5524
14 c7MeCN7326
15 d7MeCN20
16-MeCN80
a Relative to the starting material and determined by proton nuclear magnetic resonance (1H NMR) (300 MHz). b The reaction was carried out under air in an open flask. c The reaction was carried out without oxygen balloon, after just sparging the solution and closing the reaction flask. d The reaction was performed in the absence of light.
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Torregrosa-Chinillach, A.; Chinchilla, R. Synthesis of Xanthones, Thioxanthones and Acridones by a Metal-Free Photocatalytic Oxidation Using Visible Light and Molecular Oxygen. Molecules 2021, 26, 974. https://doi.org/10.3390/molecules26040974

AMA Style

Torregrosa-Chinillach A, Chinchilla R. Synthesis of Xanthones, Thioxanthones and Acridones by a Metal-Free Photocatalytic Oxidation Using Visible Light and Molecular Oxygen. Molecules. 2021; 26(4):974. https://doi.org/10.3390/molecules26040974

Chicago/Turabian Style

Torregrosa-Chinillach, Alejandro, and Rafael Chinchilla. 2021. "Synthesis of Xanthones, Thioxanthones and Acridones by a Metal-Free Photocatalytic Oxidation Using Visible Light and Molecular Oxygen" Molecules 26, no. 4: 974. https://doi.org/10.3390/molecules26040974

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