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Article

Sustainable Access to Acridin-9-(10H)ones with an Embedded m-Terphenyl Moiety Based on a Three-Component Reaction

by
Damiano Rocchi
,
Jorge Gómez-Carpintero
,
Juan F. González
* and
J. Carlos Menéndez
*
Unidad de Química Orgánica y Farmacéutica, Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Molecules 2020, 25(23), 5565; https://doi.org/10.3390/molecules25235565
Submission received: 27 October 2020 / Revised: 23 November 2020 / Accepted: 25 November 2020 / Published: 27 November 2020
(This article belongs to the Special Issue New Synthetic Methods for Organic Compounds)
Browse Figures
Versions Notes

Abstract

:
A Ce(IV)-catalyzed three-component reaction between chalcones, anilines and β-ketoesters followed by a microwave-assisted thermal cyclization afforded 1,3-diaryl-1,2-dihydroacridin-9(10H)-ones. Their microwave irradiation in nitrobenzene, acting both as solvent and oxidant, afforded fully unsaturated 1,3-diarylacridin-9(10H)-ones, which combine acridin-9-(10H)one and m-terphenyl moieties. Overall, the route generates three C-C and one C-N bond and has the advantage of requiring a single chromatographic separation.

Graphical Abstract

1. Introduction

The 9-acridone heterocyclic system is present in diverse alkaloid structures such as melicopicine, melicopidine and eroxantine [1], which have been isolated from Melicopoe fareana, Sarcomelicope follicularis and Evodia xanthoxyloids, respectively. Furthermore, the 9-acridone framework can be considered a privileged structures in the field of drug discovery as many derivates of this scaffold have shown a great variety of biological activities, such as antimalarial [2], antibacterial [3], antileishmanial [4], antiviral [5], anti-inflammatory and anti-neurodegenerative [6]. Additionally, it is well known that the planarity of these compounds allows them to act as insert in DNA and RNA, making them good candidates for their use as antitumor agents [7,8]. In Figure 1 we summarize some acridone structures that have shown interesting biological activities. For example, I has shown a good antimalarial activity, II displayed cholinesterase inhibition activity, which has great relevance in Alzheimer’s disease, acronicyne III and compounds IV have antineoplastic properties. Furthermore, due to their high fluorescence quantum yields, these molecules are attracting great attention in several technological fields, such as the development of luminescent probes and photoluminescent materials [9,10,11,12].
The most common synthetic access to 9-acridones involves the formation of the nitrogen ring from N-phenylanthranilic acid derivatives obtained via Jourdan–Ullmann couplings and heterocycle formation by the use of strong acids or catalyzed by metals [13,14,15] (Scheme 1a). An alternative approach reported by Larock and coworkers is based on the nucleophilic coupling of anthranilate with benzyne, which is formed in situ from a trimethylsilylphenyl triflate and cesium fluoride (Scheme 1b) [16]. Silva et al. described a new synthetic approach for the synthesis of 2,3-diarylacridin-9-ones, with a Heck coupling reaction between a substituted styryl and quinolone moiety as key synthetic step, followed of oxidative cyclization promoted by iodine (Scheme 1c) [17]. Deng research group described a synthetic alternative, in which the merged system is generated in the last reaction step, by oxidative cyclization of o-arylamino benzophenones (Scheme 1d) [18].
In spite of significant progress in the chemistry of this heterocyclic framework [19,20], some structural types of 9-acridones of potential interest in fields such as medicinal chemistry and materials chemistry have received little attention owing to limitations in the existing synthetic methodology. In particular, 1,3-diphenylacridin-9-ones are unknown in the literature despite the fact that they combine the acridone framework with an additional attractive structural fragment, namely m-terphenyl, which is important in materials science due to its high fluorescence [21] and also shows a variety of pharmacological activities [22,23,24,25]. In this article we describe our work towards addressing this synthetic challenge according to the strategy summarized in Scheme 2, which combines a multicomponent reaction with a 6π thermal electrocyclic reaction and a dehydrogenation step.

2. Results and Discussion

The route started with the synthesis of functionalized dihydroterphenyl derivatives from chalcones, anilines and β-ketoesters (Scheme 3), using a Ce(IV) ammonium nitrate (CAN)-catalyzed three-component protocol previously described by our group [26]. These reactions proceeded generally in good yields (Table 1) and allowed the introduction of sterically and electronically diverse substituents at both phenyl radicals, as well as some heteroaryls (compounds 1j and 1k). The presence of the N-aryl side branch, which could contain either electron-releasing or electron-withdrawing groups, was the basis for the subsequent electrocyclic cyclization step.
The next step was to establish the reaction conditions for the cyclization of compounds 1 to the dihydroacridone derivatives 2. These cyclizations are mainly described in the literature from carboxylic acids or aldehydes [27,28], which would require an additional step in our synthetic sequence. Based on the hypothesis that under thermal conditions the unsaturated β-aminoester moiety would provide an α-iminoketene intermediate I with loss of methanol, partially supported by the work of Wentrup et al. on the synthesis of 1-azafulven-6-one from pyrrole 2-carboxylic acid under flash vacuum pyrolysis [29,30], we decided to explore the ring-closing reaction of compounds 1 via a 6π electrocyclization reaction (Scheme 4). Based on our previous experience on microwave-enhanced cyclization reactions [30,31], we investigated the reactivity of the model compound 1a under microwave conditions, which have not been previously reported for the synthesis of acridones, although they have been used in the classical Gould-Jacobs synthesis of 4-quinolones from anilines and ethyl ethoxymethylenemalonate [32,33,34], as shown in Scheme 4a. After a brief study of the parameter set, we found the optimal reaction conditions, which involved heating up to 250 °C for 90 min, using dimethylformamide as a solvent and an irradiation power of 200 W. The reaction was then concentrated and the residue was crushed with diethyl ether to furnish compound 2a in 94% yield. In view of this excellent result, we extended the scope of this reaction to the full dihydroacridine library, with no clear-cut substituent effects being observed (Scheme 4b and Table 2). Compound 2h, containing a nitro group at para position of the Ar2 ring, could not be isolated due its aromatization to 3h under the cyclization reaction conditions. This can be due to the ability of the aromatic nitro group to participate as an intermediate in single electron-transfer processes, which facilitate molecular oxygen-promoted dehydrogenation reactions [35].
Finally, we investigated the aromatization of compounds 2 to the corresponding 1,3-diarylacridin-9-ones 3 (Scheme 5). The optimization of the reaction conditions was carried out on compound 2a as substrate and several dehydrogenating agents were tested. Palladium supported on carbon, manganese oxide in toluene at reflux conditions were tried without success. N-bromosuccinimide was also used tried as an aromatizing agent via halogenation-elimination [31] but these conditions also failed. DDQ in toluene (at room temperature, 120 min) and nitrobenzene (microwave, 250 °C, 90 min) were successful dehydrogenating reagents but the latter gave a higher yield and allowed a simpler purification process, as the reaction mixture could be purified by concentration in vacuo followed by trituration of the residue with diethyl ether to give the purified product by simple filtration. These conditions were applied to the whole compound library, with the results shown in Table 3.
To summarize, we have developed a method that affords 9-acridone derivatives containing an embedded m-terphenyl substructure with the generation of two rings, three carbon-carbon and one carbon-nitrogen bonds (Scheme 6). This process provides a very efficient access in two steps to 1,2-dihydroacridin-9-one derivatives, which are almost unknown in the literature [36] and not at all with the 1,3-diaryl substitution found in compounds 2. Our method also allows the efficient synthesis of the fully unsaturated compounds 3 by adding a simple dehydrogenation step to the sequence.
One important aspect of our method is its relevance in terms of sustainability. On one hand, atom economy is high (e.g., 81% for 2a and 80% for 3a); on the other, the use of organic solvents is minimized by the fact that the second and third steps of the route yield products with sufficient purity to allow purification by simple precipitation, thus avoiding the waste generation associated to chromatographic processes.

3. Materials and Methods

3.1. General Experimental Information

All reagents and solvents were of commercial quality and were used as received. Reactions were monitored by TLC analysis, on Merck silica gel-G aluminum plates with fluorescent indicator. Melting points were measured in open capillary tubes and are uncorrected. A CEM Discover microwave synthesizer with microwave power maximum level of 300 W and microwave frequency of 2455 MHz was employed for the microwave-assisted reactions. The 1H-NMR, 13C-NMR and CH-correlation spectra were recorded on a Bruker (Avance) 250 MHz or 500 MHz NMR instrument maintained by the CAI de Resonancia Magnética Nuclear, Universidad Complutense, using CDCl3, d6-DMSO or CD3OD as solvents and residual non-deuterated solvents as internal standards. Topspin (Bruker) or Mestrenova (Mestrelab) software packages were used throughout for data processing; chemical shifts are given in parts per million (δ-scale) and coupling constants are given in Hertz. Subjective 13C-NMR assignments are based on 2d_NMR experiments for representative compounds, summarized in the Supporting Information. Combustion microanalyses were performed by the CAI de Microanálisis Elemental, Universidad Complutense, on a Leco 932 CHNS analyzer. IR spectra were recorded on a Perkin Elmer Paragon 1000 FT-IR instrument using thin films placed on a KBr disk, which were obtained by evaporation of organic solvent solution of the compounds.

3.2. General Procedure for the Synthesis of 2,4-Diaryl-2,3-dihydroanthranilates 1

To a stirred solution of ethyl acetoacetate (311.0 to 974.8 mg, 2.39 to 7.49 mmol) and aniline (281.3 to 906.8 mg, 3.02 to 9.74 mmol, 1.3 eq) in ethanol (5 mL) was added CAN (65.5 mg, 0.12 mmol, 5 mol%). Stirring was continued for 30 min at room temperature. The appropriate chalcone (730 mg to 2.0 g, 2.63 to 8.24 mmol, 1.1 eq) was then added to the stirred solution and the mixture was heated under reflux for 8 h. After completion of the reaction, as indicated by TLC, the mixture was dissolved in ether (30 mL), washed with water, brine, dried (anhydrous Na2SO4) and the solvent was evaporated under reduced pressure. The final products were purified by flash silica column chromatography eluting with a petroleum ether-ethyl acetate mixture (9/1, v/v). Compounds 1a–k were known in the literature [26]. Characterization data for new compounds are given below (see Supplementary Materials). Compound numbering used in the assignment of 13C-NMR signals is also given.
Molecules 25 05565 i010
Ethyl 4″-methoxy-5′-(phenylamino)-2′,3′-dihydro-[1,1′:3′,1″-terphenyl]-4″-carboxylate (1l). Prepared from 1.78 g (7.45 mmol) of the corresponding chalcone. Yield: 2.7 g (6.26 mmol, 84%) as a yellow solid. Mp 105 °C. IR (cm−1): 3237, 3053, 2984, 2108, 1736, 1639. 1H-NMR (250 MHz, CDCl3) δ 10.64 (s, 1H), 7.27–7.15 (m, 6H), 7.12–7.07 (m, 2H), 7.06–6.99 (m, 3H), 6.70–6.62 (m, 2H), 6.56 (d, J = 2.8 Hz, 2H), 4.21 (dd, J = 8.5, 1.7 Hz, 1H), 4.03 (m, 2H), 3.64 (s, 3H), 3.11 (ddd, J = 16.6, 8.4, 2.9 Hz, 1H), 2.87 (dd, J = 16.6, 1.7 Hz, 1H), 1.10 (t, J = 7.1 Hz, 3H). 13C-NMR (63 MHz, CDCl3) δ 170.3 (CO), 156.0 (C-4″), 151.0 (C-5′), 144.1 (C-1″′), 140.0 (C-1′), 140.0 (C-1), 137.1 (C1″), 129.2 (C-5″′ and 3″′), 128.6 (C-3 and 5), 128.5 (C-2″ and C-6″), 128.3 (C-4), 125.9 (C-6 and C-2), 123.8 (C-4″′), 123.2, (C-6″′ and 2″′)118.0 (C6′), 113.5 (C-3″and C-5″), 95.7 (C-4′), 59.5(CH3-CH2O), 55.2 (MeO), 36.0 (C-3′), 34.8 (C-2″), 14.5 (CH3-CH2O). Anal. Calc. for C28H27O3N: C, 79.03; H, 6.40; N, 3.29. Found C, 78.83; H, 6.18; N, 3.09.
Ethyl 4″-chloro-5′-(phenylamino)-2′,3′-dihydro-[1,1′:3′,1″-terphenyl]-4′-carboxylate (1m). Prepared from 2.0 g (8.24 mmol) of the corresponding chalcone. Yield: 2.7 g (6.26 mmol, 76%) as a yellow solid. Mp: 120 °C. IR (cm−1): 3224, 3038, 2974, 2098, 1734, 1640. 1H-NMR (250 MHz, CDCl3) δ 10.76 (s, 1H), 7.38–7.06 (m, 14H), 6.64 (d, J = 2.8 Hz, 1H), 4.35–4.26 (m, 1H), 4.22–3.98 (m, 2H), 3.21 (ddd, J = 16.7, 8.6, 2.9 Hz, 1H), 2.92 (dd, J = 16.7, 1.7 Hz, 1H), 1.16 (t, J = 7.1 Hz, 3H). 13C-NMR (63 MHz, CDCl3) δ 170.2 (CO), 151.5 (C-5′), 144.0 (C-1″′), 143.7 (C-1″), 139.8 (C-1′), 131.8 (C-1), 129.3 (C-4″), 128.9 (C-5″′ and 3″′), 128.8 (C-2″ and C-6″), 128.8 (C-3″ and C-5″), 128.4 (C-3 and 5), 126.0 (C-2, C-4 and C-6), 124.1 (C-4″′), 123.4 (C-2″′ and 6″′)), 118.1 (C-6′), 94.7 (C4′), 59.6 (CH3-CH2O), 36.5 (C-3′), 34.6 (C-2′), 14.6 (CH3-CH2O). Anal. Calc. for C27H24O2NCl C, 75.43; H, 5.63; N, 3.26. Found C, 75.39; H, 5.54; N, 3.26.
Ethyl 2″,4,4″-trimethoxy-5′-(phenylamino)-2′,3′-dihydro-[1,1′:3′,1″-terphenyl]-4′-carboxylate (1n). Prepared from 1.0 g (3.35 mmol) of the corresponding chalcone. Yield: 1.1 g (2.31 mmol, 69%) as a pale yellow solid (Mp: 110 °C. IR (cm−1): 3260, 2952, 2838, 2115, 1737, 1640.1H-NMR (250 MHz, CDCl3) δ 10.82 (s, 1H), 7.35 (dd, J = 8.4, 7.2 Hz, 2H), 7.28–7.16 (m, 4H), 7.11 (d, J = 7.3 Hz, 1H), 6.92 (dd, J = 8.0, 0.7 Hz, 1H), 6.83–6.77 (m, 2H), 6.58 (d, J = 2.9 Hz, 1H), 6.39 (d, J = 8.2 Hz, 2H), 4.25 (dt, J = 8.0, 1.2 Hz, 1H), 4.22–4.04 (m, 2H), 3.79 (s, 6H), 3.70 (s, 3H), 3.21 (ddd, J = 16.6, 8.3, 2.9 Hz, 1H), 2.87 (dd, J = 16.7, 1.7 Hz, 1H), 1.22 (t, J = 7.1 Hz, 3H). 13C-NMR (63 MHz, CDCl3) δ 170.7 (CO), 161.2 (C-4), 158.7 (C-4″), 158.1 (C-6″), 151.8 (C5′), 143.7 (C-1″′), 140.4 (C-1′), 137.8, 130.0 (C1, C1′, C1″ or C1″′), 129.3 (C-6, 2, 5″′ and 2″′), 128.8 (C-1 and C-2″), 123.7 (C-4″′), 123.6 (C-2″′ and 6″′), 123.3 (C-1″), 119.9 (C-6′), 113.6 (C-3 and C-5), 104.6 (C-3″), 99.2 (C-5″), 95.3 (C4′), 59.6 (CH3-CH2O), 55.8 (MeO), 55.7 (MeO), 55.6 (MeO), 36.9 (C-3′), 36.5 (C-2′) 14.5 (CH3-CH2O). Anal. Calc. for C30H31O5N C, 74.21; H, 6.44; N, 2.88. Found C, 73.89; H, 6.24; N, 2.90.
Ethyl 4,4″-dichloro-5′-(phenylamino)-2′,3′-dihydro-[1,1′:3′,1″-terphenyl]-4′-carboxylate (1o). Prepared from 730 mg (2.63 mmol) of the corresponding chalcone. Yield: 720 mg (1.55 mmol, 59%) as a yellow solid. Mp: 142 °C. IR (cm−1): 3219, 3056, 2976, 1898, 2099, 1639. 1H-NMR (250 MHz, CDCl3) δ 10.83 (s, 1H), 7.49–7.15 (m, 13H), 6.70 (d, J = 2.8 Hz, 1H), 4.38 (dd, J = 8.5, 1.7 Hz, 1H), 4.30–4.10 (m, 2H), 3.28 (ddd, J = 16.6, 8.5, 2.9 Hz, 1H), 2.95 (dd, J = 16.6, 1.8 Hz, 1H), 1.26 (t, J = 7.1 Hz, 3H). 13C-NMR (63 MHz, CDCl3) δ 170.3 (CO), 151.4 (C-5′), 143.7 (C-1″′), 142.9 (C-1″), 139.9 (C-1′), 138.4 (C-1), 134.9 (C-4), 132.2 (C-4″), 129.6 (C-3″′ and C-5″′), 129.2 (C-2″ and 6″), 129.0 (C-3 and 5), 128.6 (C-3″ and 5″), 127.4 (C-2 and C-6), 124.5 (C-4″′), 123.6 (C-2″′ and 6″′), 118.7 (C-6′), 95.1 (C-4′), 59.9 (CH3-CH2O), 36.7 (C-2′), 34.8 (C-3′), 14.8 (CH3-CH2O). Anal. Calc. for C27H23O2NCl2 C, 69.83; H, 4.99; N, 3.02. Found C, 69.51; H, 4.86; N, 3.02.

3.3. General Procedure for the Synthesis of 1,3-Diaryl-1,2-dihydroacridin-9(10H)-ones 2

A microwave tube containing a solution of the suitable compound 1 (150 to 474 mg, 0.3 to 1.0 mmol) in dimethylformamide (3 mL), was closed and placed in the cavity of a CEM Discover focused microwave oven. The reaction mixture was heated with a maximum power of 200 W and a temperature gradient was programmed to achieve 250 °C starting from room temperature over 5 min. Then temperature was kept constant at 250 °C, by microwave irradiated for 90 min. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude mixture was washed with cool chloroform (3 mL) and the precipitate obtained was filtered to obtain the desired product. Compound 2h was not obtained and its dehydrogenation derivative 3h was isolated instead. Compound numbering used in the assignment of 13C-NMR signals is given below.
Molecules 25 05565 i011
1,3-Diphenyl-1,2-dihydroacridin-9(10H)-one (2a). Prepared from compound 1a (396 mg, 1.0 mmol). Yield: 328 mg (0.94 mmol, 94%); pale yellow solid. Mp: 287–288 °C. IR νmax (film): 3064, 3027, 2874, 1623, 1572, 1541 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.83 (s, 1H), 8.06 (dd, J = 8.1, 1.1 Hz, 1H), 7.68–7.60 (m, 1H), 7.59–7.52 (m, 3H), 7.48–7.36 (m, 3H), 7.33–7.23 (m, 2H), 7.23–7.14 (m, 3H), 7.14–7.07 (m, 1H), 6.89 (d, J = 2.6 Hz, 1H), 4.61 (d, J = 7.7 Hz, 1H), 3.25 (ddd, J = 17.7, 7.7, 2.6 Hz, 1H), 3.08 (dd, J = 17.4, 1.3 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 174.3 (CO), 145.3 (C-15), 144.5 (C-19), 143.6 (C-3), 139.3(C-12), 138.8 (C-19), 131.4 (C-9), 129.1 (C-22), 128.9 (C-21), 128.6 (C-17), 127.1 (C-16), 126.1 (C-18), 125.5 (C-20), 125.1 (C-7), 125.0 (C-11), 122.8 (C-10), 118.0 (C-8), 117.2 (C-4), 113.7 (C-14), 34.0 (C-1), 33.8 (C-2). Anal. Calc. for C25H19NO (M = 349.42): C, 85.93; H, 5.48; N, 4.01; found: C, 85.96; H, 5.52; N, 4.07.
7-(Dimethylamino)-1,3-diphenyl-1,2-dihydroacridin-9(10H)-one (2b). Prepared from compound 1b (439 mg, 1.0 mmol). Yield: 377 mg, (0.96 mmol, 96%); yellow solid. Mp: 299–300 °C. IR νmax (film): 2863, 2788, 1612, 1566, 1473 cm−1. 1H-NMR (500 MHz, DMSO-d6) δ 11.67 (s, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.46 (d, J = 9.1 Hz, 1H), 7.42 (t, J = 7.4 Hz, 2H), 7.40–7.34 (m, 1H), 7.27 (dd, J = 9.1, 2.9 Hz, 1H), 7.22 (d, J = 7.3 Hz, 3H), 7.14 (t, J = 7.5 Hz, 2H), 7.11–7.05 (m, 1H), 6.86 (d, J = 2.7 Hz, 1H), 4.63 (d, J = 8.2 Hz, 1H), 3.25 (ddd, J = 17.1, 8.4, 2.7 Hz, 1H), 3.07 (d, J = 16.3 Hz, 1H), 2.94 (s, 6H). 13C-NMR (126 MHz, DMSO-d6) δ 174.2 (CO), 147.7 (C-7), 145.8 (C-15), 145.0 (C-19), 142.8 C10, 139.8 (C-14), 132.2 (C-3), 129.7 (C-22), 129.7 (C-21), 128.8 (C-17), 127.9 (C-16), 127.1 (C-18), 126.7 (C-20), 126.2 (C-7), 120.2 (C-9), 119.8 (C-8), 118.3 (C-4), 113.0(C-12), 105.4 (C-11), 41.4 (Me2N), 34.8(C-1), 34.8 (C-2). Anal. Calc. for C27H24N2O (M = 392.49): C, 82.62; H, 6.16; N, 7.14; found: C, 82.59; H, 6.13; N, 7.17.
7-Fluoro-1,3-diphenyl-1,2-dihydroacridin-9(10H)-one (2c). Prepared from compound 1c (414 mg, 1.0 mmol). Yield: 316 mg (0.86 mmol, 86%); pale yellow solid. Mp: 294–295 °C. IR νmax (film): 2939, 2856, 2647, 1628, 1581 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.99 (s, 1H), 7.72 (dd, J = 9.5, 2.8 Hz, 1H), 7.68–7.51 (m, 5H), 7.49–7.37 (m, 3H), 7.26–7.16 (m, 2H), 7.15–7.08 (m, 2H), 6.90 (d, J = 2.6 Hz, 1H), 4.62 (d, J = 7.5 Hz, 1H), 3.33–3.23 (m, 1H), 3.10 (dd, J = 17.4, 1.3 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 173.5 (CO), 158.2 (d, J = 484.0 Hz) (C-10), 145.7 (C-5), 144.3 (C-7), 143.8 (C-15), 138.7 (C-19), 136.0 (C-3), 129.2 (C-12), 128.9 (C-21), 128.1(C-22), 127.0 (C-17), 126.2 (C-20), 126.1 (C-16), 125.5 (C-18), 120.6 (d, J = 51.6 Hz) (C-9), 120.0 (C-8), 117.0 (C-4), 113.1 (C-14), 109.0 (d, J = 50.4 Hz) (C-11), 33.9(C-1), 33.8 (C-2). Anal. Calc. for C25H18FNO (M = 367.41): C, 81.72; H, 4.94; N, 3.81; found: C, 81.68; H, 4.93; N, 3.76.
7-Chloro-1,3-diphenyl-1,2-dihydroacridin-9(10H)-one (2d). Prepared from compound 1d (430 mg, 1.0 mmol). Yield: 288 mg, (0.75 mmol, 75%); pale yellow solid. Mp: 275–276 °C. IR νmax (film): 3060, 2923, 2887, 1620, 1542 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 12.01 (s, 1H), 7.99 (d, J = 2.3 Hz, 1H), 7.67 (dd, J = 8.8, 2.4 Hz, 1H), 7.62–7.54 (m, 3H), 7.49–7.35 (m, 4H), 7.20 (dd, J = 10.5, 7.4 Hz, 4H), 7.14–7.08 (m, 1H), 6.88 (d, J = 2.5 Hz, 1H), 4.58 (d, J = 7.5 Hz, 1H), 3.27 (d, J = 8.3 Hz, 1H), 3.09 (d, J = 16.5 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 173.1 (CO), 146.0 (C-5), 144.2 (C-7), 138.7 (C-15), 137.9 (C-19), 131.5 (C-17), 129.2 (C-12), 129.0 (C-3), 128.1 (C-9), 127.4 (C-22), 127.0 (C-21), 126.1 (C-17), 126.0 (C-16), 125.6 (C-18), 124.0 (C-20), 122.8 (C-11), 120.5 (C-8), 117.0 (C4), 114.1 (C14), 33.9 (C1), 33.8 (C2). Anal. Calc. for C25H18ClNO (M = 383.87): C, 78.22; H, 4.73; N, 3.65; found: C, 78.18; H, 4.75; N, 3.61.
7-Bromo-1,3-diphenyl-1,2-dihydroacridin-9(10H)-one (2e). Prepared from compound 1e (474 mg, 1.0 mmol). Yield: 330 mg, (0.77 mmol, 77%); pale yellow solid. Mp: 269–270 °C. IR νmax (film): 3060, 2899, 2803, 1619, 1540 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 12.02 (s, 1H), 8.15 (d, J = 2.3 Hz, 1H), 7.79 (dd, J = 8.8, 2.3 Hz, 1H), 7.56 (t, J = 8.9 Hz, 3H), 7.48–7.35 (m, 3H), 7.21 (t, J = 8.8 Hz, 2H), 7.13 (dd, J = 6.5, 4.7 Hz, 2H), 6.89 (d, J = 2.2 Hz, 1H), 4.61 (d, J = 7.8 Hz, 1H), 3.27 (d, J = 8.4 Hz, 1H), 3.10 (d, J = 17.4 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 173.0 (CO), 146.0 (C-5), 144.2 (C-7), 138.7 (C-15), 138.2 (C-19), 134.1 (C-9), 131.6 (C-12), 129.2 (C-3), 129.0 (C-11), 128.1 (C-21), 127.2 (C-17 and C-22), 127.0 (C-20), 126.4 (C-16), 126.2 (C-18), 125.6 (C-8), 120.7 (C-10), 120.6 (C-8), 115.4 (C4), 114.2 (C14), 33.9 (C1), 33.8 (C2). Anal. Calc. for C25H18BrNO (M = 428.32): C, 70.10; H, 4.24; N, 3.27; found: C, 70.06; H, 4.28; N, 3.21.
6,8-Dichloro-1,3-diphenyl-1,2-dihydroacridin-9(10H)-one (2f). Prepared from compound 1f (464 mg, 1.0 mmol). Yield: 347 mg, (0.83 mmol, 83%); yellow solid. Mp: 199–200 °C. IR νmax (film): 3255, 3058, 2896, 1628, 1579 cm−1. 1H-NMR (250 MHz, CDCl3-d6) δ 8.38 (s, 1H), 7.46–7.32 (m, 5H), 7.26 (s, 1H), 7.22–7.05 (m, 4H), 6.49 (d, J = 2.7 Hz, 1H), 6.41 (d, J = 1.7 Hz, 1H), 6.18 (d, J = 1.8 Hz, 1H), 4.70 (d, J = 7.8 Hz, 1H), 3.30 (ddd, J = 17.3, 8.7, 2.7 Hz, 1H), 3.12 (dd, J = 17.4, 1.5 Hz, 1H). 13C-NMR (63 MHz, CDCl3-d6) δ 179.0 (CO), 152.7 (C-7), 146.4 (C-5), 143.6(C-11), 143.4(C-9), 142.2 (C-15), 139.0 (C-19), 129.0 (C-3), 128.7(C-10), 128.3 (C-17 and 22), 127.1 (C-21), 126.5(C-12), 125.7 (C-20 and C-18), 116.6 (C-4), 114.9 (C14), 110.2 (C-14, 102.0 (C-8), 101.1 (C-14), 35.0 (C1), 34.6 (C2). Anal. Calc. for C25H17Cl2NO (M = 418.31): C, 71.78; H, 4.10; N, 3.35; found: C, 71.82; H, 4.16; N, 3.31.
6,8-Dimethyl-1,3-diphenyl-1,2-dihydroacridin-9(10H)-one (2g). Prepared from compound 1g (424 mg, 1.0 mmol). Yield: 310 mg, (0.82 mmol, 82%); pale yellow solid. Mp: 275–276 °C. IR νmax (film): 3238, 3079, 2955, 2918, 1621, 1585 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.46 (s, 1H), 7.57–7.49 (m, 2H), 7.39 (td, J = 8.1, 2.4 Hz, 3H), 7.20 (dt, J = 5.6, 2.9 Hz, 3H), 7.17–7.06 (m, 4H), 6.84 (d, J = 2.6 Hz, 1H), 6.79 (s, 1H), 4.52 (d, J = 10 Hz), 3.31–3.16 (m, 1H), 3.02 (d, J = 17.3 Hz, 1H), 2.75 (s, 3H), 2.35 (s, J = 5.7 Hz, 3H). 13C-NMR (63 MHz, DMSO-d6) δ 176.8 (CO), 144.7 (C-7), 144.4 (C-9), 142.2 (C-5), 141.1 (C-15), 140.3 (C-12), 139.0 (C-3), 138.9 (C-19), 128.9 (C-17), 128.0 (C-21), 127.1 (C-22), 126.9 (C-16), 125.9 (C-20), 125.4 (C-18), 121.4 (C-10), 117.1 (C-12), 115.5 (C-4), 114.6 (C-14), 34.4 (C-1), 33.9 (C-2), 23.2 (Me), 21.1 (Me). Anal. Calc. for C27H23NO (M = 377.48): C, 85.91; H, 6.14; N, 3.71; found: C, 85.86; H, 6.16; N, 3.67.
3-(4-Bromophenyl)-1-phenyl-1,2-dihydroacridin-9(10H)-one (2i). Prepared from compound 1i (474 mg, 1.0 mmol). Yield: 407 mg, (0.95 mmol, 95%); yellow solid. Mp: 317–318 °C. IR νmax (film): 2774, 1631, 1578, 1487 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.85 (s, 1H), 8.06 (d, J = 7.3 Hz, 1H), 7.68–7.59 (m, 3H), 7.53 (t, J = 8.2 Hz, 3H), 7.36–7.05 (m, 6H), 6.91 (d, J = 2.5 Hz, 1H), 4.60 (d, J = 7.9 Hz, 1H), 3.31–3.20 (m, 1H), 3.03 (d, J = 16.8 Hz, 1H). 13C-NMR (126 MHz, DMSO-d6) δ 174.1 (CO), 144.2 (C-5), 143.8 (C-15), 143.0 (C-7), 139.1 (C-3), 137.9 (C-19), 131.6 (C-21), 131.0 (C-9), 127.7 (C-17), 127.3 (C-16), 126.7 (C-20), 125.7 (C-12), 124.9 (C-18), 124.8 (C-11), 122.4 (C-10), 121.9 (C-22), 117.7 (C-8), 117.7 (C4), 113.7 (C14), 33.6 (C1), 33.6 (C2). Anal. Calc. for C25H18BrNO (M = 428.32): C, 70.10; H, 4.24; N, 3.27; found: C, 70.07; H, 4.26; N, 3.23.
1-Phenyl-3-(thiophen-2-yl)-1,2-dihydroacridin-9(10H)-one (2j). Prepared from compound 1j (402 mg, 1.0 mmol). Yield: 334 mg, (0.94 mmol, 94%); orange solid. Mp: 304–305 °C. IR νmax (film): 3068, 2923, 1619, 1572 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.82 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.64 (dd, J = 11.2, 5.9 Hz, 2H), 7.53 (d, J = 8.2 Hz, 1H), 7.46 (d, J = 3.4 Hz, 1H), 7.35–7.06 (m, 7H), 6.86 (s, 1H), 4.61 (br s, 1H), 3.21 (br s, 2H). 13C-NMR (63 MHz, DMSO-d6) δ 174.4 (CO), 162.7 (C-5), 144.7 (C-15), 143.7(C-3), 143.1 (C-7), 139.6 (C-19), 139.5 (C-9), 131.7 (C-22), 128.9 (C-17), 128.4 (C-21), 128.4 (C-12), 127.4 (C-20), 127.1 (C-16), 126.4 (C-11), 125.4 (C-18), 123.1 (C-10), 118.3 (C-4), 115.0 (C-8), 114.1 (C14), 34.1 (C1), 34.0 (C2). Anal. Calc. for C23H17NOS (M = 355.45): C, 77.72; H, 4.82; N, 3.94; found: C, 77.67; H, 4.84; N, 3.91.
1,3-Di(furan-2-yl)-1,2-dihydroacridin-9(10H)-one (2k). Prepared from compound 1k (375 mg, 1.0 mmol). Yield: 303 mg (0.92 mmol, 92%); pale yellow solid. Mp: 282–283 °C. IR νmax (film): 3066, 2911, 1621, 1562 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.84 (s, 1H), 8.08 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 1.6 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.52 (d, J = 7.8 Hz, 1H), 7.43 (s, J = 0.9 Hz, 1H), 7.29 (t, J = 8.0 Hz, 1H), 6.95 (d, J = 3.4 Hz, 1H), 6.84 (d, J = 2.3 Hz, 1H), 6.62 (dd, J = 3.4, 1.8 Hz, 1H), 6.19 (dd, J = 3.1, 1.8 Hz, 1H), 5.76 (d, J = 3.2 Hz, 1H), 4.62 (d, J = 7.4 Hz, 1H), 3.16 (dd, J = 17.1, 1.1 Hz, 1H), 2.91 (ddd, J = 17.1, 8.0, 2.5 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 173.8 (CO), 156.3 (C-15), 152.2 (C-5), 145.1 (C-19), 143.5 (C-22), 141.5 (C-18), 139.3 (C-7), 134.1 (C-3), 131.4 (C-9), 125.1 (C-12), 125.0 (C-11), 122.8 (C-10), 118.0 (C4), 112.5(C-8), 112.5 (C-21), 111.4 (C-20), 111.4 (C-14), 110.2 (C-17), 105.1 (C-16), 28.7 (C1), 28.2 (C2). Anal. Calc. for C21H15NO3 (M = 329.35): C, 76.58; H, 4.59; N, 4.25; found: C, 76.53; H, 4.62; N, 4.28.
3-(4-Methoxyphenyl)-1-phenyl-1,2-dihydroacridin-9(10H)-one (2l). Prepared from compound 1l (200 mg, 0.47 mmol); yield: 76 mg (0.20 mmol, 43% yield). yellow solid Mp: 242 °C. IR νmax (film): 3391, 2990, 2770, 2106, 1607. 1H-NMR (250 MHz, DMSO-d6) δ 11.87 (s, 1H), 8.08 (dd, J = 8.1, 1.4 Hz, 1H), 7.68–7.53 (m, 4H), 7.48–7.37 (m, 3H), 7.29 (ddd, J = 8.1, 6.7, 1.3 Hz, 1H), 7.17–7.08 (m, 2H), 6.90 (d, J = 2.5 Hz, 1H), 6.78–6.65 (m, 2H), 4.57 (d, J = 7.8 Hz, 1H), 3.63 (s, 3H), 3.32–3.19 (ddd, J = 17.0, 8.3, 2.5 Hz, 1H), 3.10–3.01 (d, J = 17.0 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 174.7 (CO), 157.9(C-22), 145.7 (C-5), 143.8 (C-15), 139.6 (C-7), 139.1 (C-3), 136.7 (C-9), 131.7 (C-19), 129.4 (C-20), 129.3 (C-17), 128.3 (C-16 and C-18), 125.8 C-12), 125.4 (C-11), 123.1 (C-10), 118.3 (C-8), 117.4 (C4), 114.5 (C-21), 113.7 (C14), 55.2 (OMe), 34.4 (C1), 33.3 (C2). Anal. Calc. for C26H21O2N C, 82.30; H, 5.58; N, 3.69. Found C, 80.91; H, 5.47; N, 3.85.
3-(4-Chlorophenyl)-1-phenyl-1,2-dihydroacridin-9(10H)-one (2m). Prepared from compound 1m (300 mg, 0.7 mmol); yield: 140 mg (0.4 mmol, 52% yield). Brown solid Mp: 278 °C. IR νmax (film): 3252, 3056, 2874, 2765, 2107, 1700, 1620. 1H-NMR (250 MHz, DMSO-d6) δ 11.90 (s, 1H), 8.06 (dd, J = 8.1, 1.4 Hz, 1H), 7.69–7.51 (m, 5H), 7.50–7.37 (m, 3H), 7.29 (m, 2H), 7.20 (m, 2H), 6.90 (d, J = 2.5 Hz, 1H), 4.59 (d, J = 8.1 Hz, 1H), 3.24 (dd, J = 8.5, 2.3 Hz, 1H), 3.07 (dd, J = 17.6, 1.4 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 174.6 (CO), 145.6 (C-5), 144.0 (C-15), 143.8 (C-7), 139.6 (C-3), 139.0 (C-9), 131.8(C-19), 131.0 C-22), 129.5 (C-21), 129.3 (C-17), 129.3 (C-20 y C-16), 128.3 (C-11), 125.9 (C-12), 125.4 (C-18), 123.2 (C-10), 118.4 (C-8), 117.5 (C4), 113.6 (C14), 34.0 (C1), 33.6 (C2). Anal. Calc. for C25H18ONCl C, 78.22; H, 4.73; N, 3.65. Found C, 76.03; H, 4.85; N, 3.97.
3-(2,4-Dimethoxyphenyl)-1-(4-methoxyphenyl)-1,2-dihydroacridin-9(10H)-one (2n). Prepared from compound 1n (150 mg, 0.3 mmol); 58 mg (0.13 mmol, 44% yield). Yellow solid Mp: 168 °C. IR νmax (film): 3214, 3066, 2932, 2829, 2118, 1603. 1H-NMR (250 MHz, DMSO-d6) δ 12.14 (s, 1H), 8.15–8.07 (m, 1H), 7.65 (dd, J = 6.2, 1.5 Hz, 2H), 7.37–7.28 (m, 1H), 7.24 (dd, J = 8.5, 1.8 Hz, 1H), 7.20–7.11 (m, 2H), 6.86 (d, J = 2.4 Hz, 1H), 6.75 (dd, J = 8.9, 2.5 Hz, 2H), 6.66–6.60 (m, 1H), 6.57 (d, J = 2.4 Hz, 1H), 4.52 (d, J = 7.7 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 3.66 (s, 3H), 3.28–3.17 (m, 1H), 2.92 (d, J = 17.3 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 161.4 (CO), 158.7 (C-22), 157.9 (C-18 and C-20), 145.6 (C-5), 144.7 (C-7), 139.5 (C-3), 136.6 (C-15), 131.7 (C-9), 129.6 (C-16), 128.4 (C-12), 125.2 (C-20), 125.0(C-11), 121.8 (C-8), 118.6 (C-17),118.4 (C4), 114.0 (C-21), 113.6 (C14), 105.6 (C-19), 99.3 (C-21′), 56.0 (OMe), 55.7 (OMe), 55.3 (OMe), 36.3 (C2), 33.5 (C1). Anal. Calc. for C28H25O4N C, 76.52; H, 5.73; N, 3.19. Found C, 75.31; H, 5.67; N, 3.38.
1,3-Bis(4-chlorophenyl)-1,2-dihydroacridin-9(10H)-one (2o). Prepared from compound 1o (173 mg, 0.3 mmol); 34 mg (0.08 mmol, 27% yield). Yellow solid Mp: 287 °C. IR νmax (film): 3252, 3059, 2749, 2681, 2113, 1624. 1H-NMR (300 MHz, DMSO-d6) δ 11.86 (s, 1H), 8.07 (dd, J = 8.1, 1.5 Hz, 1H), 7.68–7.56 (m, 3H), 7.53–7.47 (m, 2H), 7.30 (ddd, J = 8.1, 6.8, 1.1 Hz, 2H), 7.23 (s, 4H), 6.91 (d, J = 2.7 Hz, 1H), 4.60 (d, J = 8.3 Hz, 1H), 3.29–3.22 (m, 1H), 3.04 (dd, J = 17.6, 1.5 Hz, 1H). 13C-NMR (75 MHz, DMSO-d6) δ 174.7 (CO), 144.3 (C-5), 143.8 (C-15), 139.7 (C-7), 138.0 (C-3), 134.1 (C-19), 132.0 (C-18), 131.1 (C-9), 129.4 (C-22), 129.3 (C-16), 128.5 (C-17), 127.8 (C-21), 125.5 (C-20), 125.4 (C-12), 124.5 (C-11), 123.4 (C-10), 118.5 (C-8), 118.3 (C4), 113.8 (C14), 34.0 (C1), 33.7 (C2). Anal. Calc. for C25H17ONCl2 C, 71.78; H, 4.10; N, 3.35. Found C, 71.04; H, 4.20; N, 3.49.

3.4. General Procedure for the Synthesis of 1,3-diaryl-acridin-9(10H)-ones 3

A microwave tube containing a solution of the suiTable 1,3-diaryl-1,2-dihydroacridin-9(10H)-one derivatives 2 (30 to 441 mg, 0.07 to 1.0 mmol) in nitrobenzene (3 mL), was closed and placed in the cavity of a CEM Discover focused microwave oven. The reaction mixture was heated by microwave irradiation for 90 min., at 200 W and 250 °C. Then, the mixture was cooled to room temperature and the solvent was evaporated under reduce pressure. The crude mixture was washed with cool chloroform and the solid obtained was filtered to obtain compounds 3. In the cases of compounds 3k and 3n, purification required column chromatography on silica gel, eluting with petrol ether/EtOAc (7/3). Compound numbering used in the assignment of 13C-NMR signals is given below.
Molecules 25 05565 i012
1,3-Diphenylacridin-9(10H)-one (3a). Prepared from compound 2a (175 mg, 0.5 mmol). Yield: 142 mg, (0.41 mmol, 82%); brown solid. Mp: 333–334 °C. IR νmax (film): 3062, 2972, 1624, 1594 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 8.03 (d, J = 8.1 Hz, 1H), 7.79 (d, J = 8.3 Hz, 3H), 7.71 (t, J = 6.9 Hz, 1H), 7.58–7.45 (m, 4H), 7.33 (bs, 5H), 7.24–7.14 (m, 2H). 13C-NMR (63 MHz, DMSO-d6) δ 176.5 (CO), 144.1 (C-5), 143.5 (C-3), 143.1 (C-7), 142.9 (C-19), 140.4 (C-15), 138.8 (C-1), 133.3 (C-9), 129.3 (C-21), 128.7 (C_17), 127.1 (C-20, C-16 and C-22) (3 overlapped signals), 126.3 (C-18), 126.2 (C-11), 123.2 (C-14), 121.9 (C-10), 121.0 (C-12), 116.8 (C-8), 116.6 (C-4), 114.5 (C-2). Anal. Calc. for C25H17NO (M = 347.41): C, 86.43; H, 4.93; N, 4.03; found: C, 85.94; H, 5.03; N, 4.06.
7-(Dimethylamino)-1,3-diphenylacridin-9(10H)-one (3b). Prepared from compound 2b (196 mg, 0.5 mmol). Yield: 156 mg, (0.40 mmol, 80%); brown oil. IR νmax (film): 2924, 2853, 1621, 1589 cm−1. 1H-NMR (250 MHz, CDCl3) δ 8.82 (s, 1H), 7.64 (dd, J = 7.9, 1.5 Hz, 2H), 7.50–7.39 (m, 8H), 7.39–7.32 (m, 2H), 7.24 (d, J = 1.7 Hz, 1H), 7.16 (d, J = 8.8 Hz, 1H), 7.01 (dd, J = 8.8, 2.7 Hz, 1H), 2.79 (s, 6H). 13C-NMR (63 MHz, CDCl3) δ 177.7 (CO), 144.9 (C-5), 144.6 (C-3), 144.0 (C-10), 143.8 (C-19), 141.8 (C-15), 139.6 (C-1), 133.2 (C-7), 129.1 (C-21), 128.5 (C-17), 128.4 (C-16), 127.5 (C-20), 127.4 (C-18), 126.6 (C-22), 124.0 (C-14), 123.9 (C_12), 122.8 (C-9), 117.5 (C-4), 116.7 (C-2), 114.3 (C-11), 105.2 (C-8), 31.3 (NMe). Anal. Calc. for C27H22N2O (M = 390.48): C, 83.05; H, 5.68; N, 7.17; found: C, 82.95; H, 6.03; N, 7.15.
7-Fluoro-1,3-diphenylacridin-9(10H)-one (3c). Prepared from compound 2c (184 mg, 0.5 mmol). Yield: 155 mg, (0.42 mmol, 85%); pale yellow solid. Mp: 320–321 °C. IR νmax (film): 3238, 3100, 2969, 1625, 1594, 1563 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.93 (bs, 1H), 7.84–7.73 (m, 3H), 7.69 (d, J = 8.0 Hz, 1H), 7.66–7.59 (m, 2H), 7.59–7.45 (m, 3H), 7.35 (bs, 5H), 7.19 (d, J = 0.8 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 175.7 (CO), 157.0 (C_10) (d, J = 240 Hz), 143.9 (C-5), 143.6 (C_3), 142.9 (C-19), 142.8 (C-15), 138.7 (C-1), 137.2 (C-7), 129.3 C-17), 128.7 (C-21), 128.7 (C-16), 127.2 (C-20), 126.3 (C-18), 123.4 (C-22), 122.5 (C-14), 122.4 (C-12), 122.1 (C-9) (d, J = 25.2 Hz), 119.4 (C-8), 115.7 (C-2), 114.5 (C-4), 110.1 (d, J = 22.7 Hz) (C-11). Anal. Calc. for C25H16FNO (M = 365.40): C, 82.18; H, 4.41; N, 3.83; found: C, 82.13; H, 4.47; N, 3.81.
7-Chloro-1,3-diphenylacridin-9(10H)-one (3d). Prepared from compound 2d (192 mg, 0.5 mmol). Yield: 145 mg, (0.38 mmol, 76%); yellow solid. Mp: 312–313 °C. IR νmax (film): 3068, 2967, 1626, 1561 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.97 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.81 (s, 1H), 7.79–7.74 (m, 3H), 7.72 (d, J = 2.5 Hz, 1H), 7.56 (dd, J = 7.9, 4.1 Hz, 3H), 7.49 (dd, J = 8.0, 3.7 Hz, 2H), 7.35 (s, 3H), 7.20 (d, J = 1.7 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 175.4 (CO), 144.1 (C-5), 143.8 (C-3), 142.8 (C-19), 139.0 (C-15), 138.7 (C-7), 133.7 (C-1), 133.3 (C-9), 129.3 (C-11), 128.8 (C-17), 128.7 (C-21), 127.2 (C-16), 127.2 (C-20), 126.4 (C-18), 125.4 (C-22), 125.1 (C-14), 123.7 (C-12), 122.7 (C-8), 119.3 (C-10), 116.4 (C-4), 114.6 (C-2). Anal. Calc. for C25H16ClNO (M = 381.85): C, 78.63; H, 4.22; N, 3.67; found: C, 78.58; H, 4.26; N, 3.63.
7-Bromo-1,3-diphenylacridin-9(10H)-one (3e). Prepared from compound 2e (214 mg, 0.5 mmol). Yield: 166 mg, (0.69 mmol, 78%); yellow solid. Mp: 276–277 °C. IR νmax (film): 3264, 3059, 2985, 1620, 1596 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.99 (s, 1H), 8.10 (d, J = 2.3 Hz, 1H), 7.83–7.79 (m, 2H), 7.76 (m, 3H), 7.58–7.52 (m, 2H), 7.52–7.46 (m, 3H), 7.38–7.33 (m, 3H), 7.20 (d, J = 1.6 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 175.3 (CO), 144.1 (C-5), 143.8 (C-3), 142.8 (C-19), 139.3 (C-7), 138.7 (C-15), 135.8 (C-1), 129.3 (C-9), 128.8 (C-11), 128.7 (C-17), 128.3 (C-21), 127.2 (C-16), 127.2 (C-20), 127.1 (C-18), 126.4 (C-229, 123.7 (C-14), 123.2 (C-12), 119.5 (C-8), 116.5 (C-10), 114.6 (C-4), 113.1 (C-2). Anal. Calc. for C25H16BrNO (M = 426.30): C, 70.43; H, 3.78; N, 3.29; found: C, 70.39; H, 3.73; N, 3.34.
6,8-Dichloro-1,3-diphenylacridin-9(10H)-one (3f). Prepared from compound 2f (209 mg, 0.5 mmol). Yield: 162 mg, (0.39 mmol, 78%); yellow solid. Mp: 281–282 °C. IR νmax (film): 3279, 3060, 2923, 1620, 1595 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.61 (s, 1H), 9.68 (d, J = 5.0 Hz, 1H), 7.75 (d, J = 7.2 Hz, 2H), 7.62 (s, 1H), 7.57–7.43 (m, 3H), 7.39–7.22 (m, 4H), 7.09 (d, J = 0.8 Hz, 1H), 6.51 (d, J = 1.0 Hz, 1H), 6.10 (d, J = 1.0 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 179.2 (CO), 153.3 (C-7), 143.7 (C-5), 143.5 (C-3), 143.4 (C-19), 143.4 (C-15), 141.9 (C-11), 139.3 (C-1), 138.7 (C-9), 129.2 (C-17), 128.7 (C-21), 128.4 (C-16), 127.2 (C-20), 127.1 (C-18), 126.2 (C-22), 123.8 (C-12), 117.4 (C-14), 113.7 (C-10), 106.0 (C-8), 99.9 (C-4), 98.9 (C-2). Anal. Calc. for C25H15Cl2NO (M = 416.30): C, 72.13; H, 3.63; N, 3.36; found: C, 72.09; H, 3.67; N, 3.31.
6,8-Dimethyl-1,3-diphenylacridin-9(10H)-one (3g). Prepared from compound 2g (189 mg, 0.5 mmol). Yield: 150 mg, (0.40 mmol, 80%); brown solid. Mp: 286–287 °C. IR νmax (film): 3021, 2962, 1593, 1534 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.42 (s, 1H), 7.76 (d, J = 7.2 Hz, 2H), 7.66 (s, 1H), 7.58–7.42 (m, 3H), 7.34 (m, 5H), 7.10 (s, 2H), 6.75 (s, 1H), 2.60 (s, 3H), 2.37 (s, 3H). 13C-NMR (63 MHz, DMSO-d6) δ 178.7 (CO), 143.8 (C-5), 143.3 (C-7), 143.0 (C-9), 142.3 (C-3), 142.1 (C-19), 142.1 (C-11), 139.9 (C-15), 139.0 (C-1), 129.2 (C.12), 128.5 (C-17), 128.5 (C-21), 127.3 (C-16), 127.1 (C-20), 126.1 (C-18), 125.4 (C-22), 123.0 (C-14), 118.6 (C-10), 118.2 (C-4), 114.3 (C-2), 113.7 (C-8), 23.2 (C9-Me), 21.3 (C11-Me). Anal. Calc. for C27H21NO (M = 375.46): C, 86.37; H, 5.64; N, 3.73; found: C, 86.32; H, 5.68; N, 3.72.
1-(4-Nitrophenyl)-3-phenylacridin-9(10H)-one (3h). Prepared from compound 1h (441 mg, 1.0 mmol). Yield: 338 mg, (0.86 mmol, 86 % overall) without the need for a separate oxidation step; pink solid. Mp: 174–175 °C. IR νmax (film): 3401, 3325, 3260, 1587, 1493 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 8.30 (s, 1H), 7.66 (d, J = 7.0 Hz, 2H), 7.46 (t, J = 7.3 Hz, 1H), 7.38 (d, J = 8.6 Hz, 3H), 7.31–7.23 (m, 1H), 7.22–7.12 (m, 5H), 6.84 (t, J = 7.2 Hz, 1H), 6.65 (d, J = 8.5 Hz, 2H). 13C-NMR (63 MHz, DMSO-d6) δ 182.3 (CO), 148.6 (C-18), 144.3 (C-15), 143.4 (C-5), 142.5 (C-3), 141.8 (C-7), 140.9 (C-19), 129.3 (C21), 128.9 (C-1), 127.7 (C-9), 127.5 (C-16), 127.4 (C-20 and 22), 126.8 (C-11 and C14), 119.9 (C-17), 117.1 (C-10), 116.0 (C-12), 114.2 (C-8), 112.9 (C-4), 112.5 (C_2). Anal. Calc. for C25H16N2O3 (M = 392.41): C, 76.52; H, 4.11; N, 7.14; found: C, 76.48; H, 4.05; N, 7.18.
3-(4-Bromophenyl)-1-phenylacridin-9(10H)-one (3i). Prepared from compound 2i (214 mg, 0.5 mmol). Yield: 179 mg, (0.42 mmol, 84%); yellow solid. Mp: 326–327 °C. IR νmax (film): 3090, 2984, 1624, 1570, 1533 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.80 (s, 1H), 8.03 (d, J = 7.1 Hz, 1H), 7.81–7.63 (m, 6H), 7.52 (d, J = 8.2 Hz, 1H), 7.41–7.29 (m, 5H), 7.20 (t, J = 7.7 Hz, 1H), 7.16 (d, J = 1.6 Hz, 1H). 13C-NMR (63 MHz, DMSO-d6) δ 176.8 (CO), 144.5 (C-5), 143.3 (C-3), 143.2 (C-7), 142.5 (C-15), 140.7 (C-19), 138.3 (C-1), 133.7 (C-9), 132.5 C-20), 129.6 (C-17), 129.0 (C-16), 127.5 (C-18), 126.6 (C-11), 126.5 (C-14), 123.3 (C-22), 122.6 (C-21), 122.3 (C-10), 121.4 (C-12), 117.2 (C-8), 117.1 (C-4), 114.8 (C-2). Anal. Calc. for C25H16BrNO (M = 426.30): C, 70.43; H, 3.78; N, 3.29; found: C, 70.39; H, 3.82; N, 3.34.
1-Phenyl-3-(thiophen-2-yl)acridin-9(10H)-one (3j). Prepared from compound 2j (178 mg, 0.5 mmol). Yield: 140 mg, (0.39 mmol, 79%); orange solid. Mp: 301–302 °C IR νmax (film): 3057, 3007, 2922, 1673, 1592 cm−1. 1H-NMR (250 MHz, DMSO-d6) δ 11.76 (s, 1H), 8.01 (dd, J = 8.1, 1.1 Hz, 1H), 7.78–7.64 (m, 4H), 7.49 (d, J = 8.1 Hz, 1H), 7.40–7.27 (m, 5H), 7.25–7.14 (m, 3H). 13C-NMR (63 MHz, DMSO-d6) δ 176.2 (CO), 144.3 (C-5), 142.9 (C-7), 142.9 (C-19), 141.7 (C-15), 140.4 (C-3), 136.8 (C-1), 133.3 (C-9), 129.0 (C-17), 128.5 (C-22), 127.8 (C-21), 127.2 (C-16), 126.3 (C-20), 126.2 (C-18), 125.9 (C-14), 122.0 (C-11), 121.5 (C-10), 121.1 (C-12), 116.8 (C-8), 116.6 (C-4), 112.5 (C-2). Anal. Calc. for C23H15NOS (M = 353.44): C, 78.16; H, 4.28; N, 3.96; found: C, 78.12; H, 4.24; N, 4.04.
1,3-Di(furan-2-yl)acridin-9(10H)-one (3k). Prepared from compound 2k (165 mg, 0.5 mmol). Yield: 126 mg, (0.38 mmol, 77%); brown solid. Mp: 195–196 °C. IR νmax (film): 3104, 2922, 1621, 1601 cm−1. 1H-NMR (250 MHz, CDCl3) δ 10.10 (s, 1H), 8.33 (d, J = 8.0 Hz, 1H), 7.63 (d, J = 1.4 Hz, 1H), 7.56–7.45 (m, 3H), 7.39 (dd, J = 8.0, 1.4 Hz, 2H), 7.11 (t, J = 7.5 Hz, 1H), 6.69 (d, J = 3.3 Hz, 1H), 6.57 (d, J = 3.0 Hz, 1H), 6.47–6.38 (m, 2H). 13C-NMR (63 MHz, CDCl3) δ 177.7 (CO), 154.5 (C-15), 152.2 (C-19), 143.6 (C-5), 142.7 (C-18), 142.2 (C-22), 140.2 (C-7), 133.9 (C-3), 133.3 (C-9), 132.5 (C-1), 127.1 (C-11), 122.7 (C-14), 121.8 (C-10), 121.1 (C-12), 117.6 (C-8), 116.7 (C-4), 112.3 (C-2), 112.1 (C-17), 111.1 (C-21), 108.4 (C-16), 108.2 (C-20). Anal. Calc. for C21H13NO3 (M= 327.33): C, 77.05; H, 4.00; N, 4.28; found: C, 77.11; H, 4.05; N, 4.32.
3-(4-Methoxyphenyl)-1-phenylacridin-9(10H)-one (3l). Prepared from compound 2l (50 mg, 0.13 mmol); Yield: 38 mg (0.10 mmol, 74% yield); yellow solid Mp: 296 °C. IR νmax (film): 3264, 3107, 2929, 2106, 1889, 1617..1H-NMR (300 MHz, CDCl3) δ 9.18 (s, 1H), 8.36 (dd, J = 8.2, 1.5 Hz, 1H), 7.69–7.59 (m, 3H), 7.55 (d, J = 1.8 Hz, 1H), 7.50–7.41 (m, 4H), 7.41–7.33 (m, 3H), 7.22 (ddd, J = 8.1, 7.0, 1.0 Hz, 1H), 6.99–6.92 (m, 2H), 3.83 (s, 3H). 13C-NMR (75 MHz, CDCl3) δ 177.1 (CO), 158.8 (C-22), 145.1 (C-5), 144.9 (C-3), 144.1 (C-7), 140.2 (C-15), 139.2 (C-1), 134.8 (C-19), 133.5 (C-9), 129.7 (C-20), 129.0 (C-17), 128.6 (C-16), 127.4 (C-18), 127.1 (C-11), 125.0 (C-14), 122.1 (C-10), 122.0 (C-12), 117.0 (C-21), 116.4 (C-8), 114.2 (C-4), 113.2(C-2), 55.2 (OMe). Anal. Calc. for C26H19O2N C, 82.74; H, 5.07; N, 3.71. Found C, 79.83; H, 5.18; N, 3.69.
3-(4-Chlorophenyl)-1-phenylacridin-9(10H)-one (3m). Prepared from compound 2m (30 mg, 0.08 mmol); Yield: 22 mg (0.06 mmol, 70% yield). Yellow solid Mp: 366 °C. IR νmax (film):3262, 3072, 2930, 2109, 1892, 1623. 1H-NMR (300 MHz, DMSO-d6) δ 11.87 (s, 1H), 8.10 (dd, J = 8.1, 1.5 Hz, 1H), 7.86 (dd, J = 7.2, 1.8 Hz, 3H), 7.78 (ddd, J = 8.5, 6.9, 1.6 Hz, 1H), 7.61 (t, J = 7.2 Hz, 3H), 7.56–7.51 (m, 1H), 7.51–7.39 (m, 4H), 7.31–7.23 (m, 2H). 13C-NMR (75 MHz, DMSO-d6) δ 176.9 (CO), 144.0 (C-5), 143.3 (C-3), 143.1 (C-7), 142.4 (C-15), 140.9 (C-19), 139.2 (C-1), 133.8 (C-9), 131.6 (C-22), 130.9 (C-21), 129.7 (C-20), 129.2 (C-17), 127.6 (C-16), 127.5 (C-18), 126.6 (C-11), 123.5 (C-14), 122.3 (C-10), 121.6 (C-12), 117.3 (C-6), 116.9 (C.4), 115.2 (C-2). Anal. Calc. for C25H16ONCl C, 78.64; H, 4.22; N, 3.67. Found C, 76.90; H, 4.26; N, 3.67.
3-(2,4-Dimethoxyphenyl)-1-(4-methoxyphenyl)-acridin-9(10H)-one (3n). Prepared from compound 2n (30 mg, 0.07 mmol); Yield: 24 mg (0.05 mmol, 77% yield). Orange solid Mp: 281 °C. IR νmax (film): 3263, 3105, 2954, 2831, 2110, 1887, 1611. 1H-NMR (300 MHz, CDCl3) δ 9.37 (s, 1H), 8.24 (dd, J = 8.2, 1.5 Hz, 1H), 7.57 (d, J = 1.7 Hz, 1H), 7.52 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.36 (d, J = 8.3 Hz, 1H), 7.31–7.22 (m, 3H), 7.16–7.08 (m, 2H), 6.93–6.84 (m, 2H), 6.51–6.44 (m, 2H), 3.78 (s, 3H), 3.77 (s, 3H), 3.74 (s, 3H). 13C-NMR (75 MHz, CDCl3) δ 176.8 (CO), 161.3 (C-20), 158.8 (C-22), 157.8 (C-18), 142.9 (C-5), 142.6 (C-3), 141.9 (C-7), 140.0 (C-1), 134.9 (C-9), 133.3 (C-15), 131.5 (C-16), 129.9 (C-20), 127.5 (C-11), 127.0 (C-14 and C-19), 121.9 (C-10), 121.8 (C-12), 121.4 (C-17), 116.7 (C-8), 116.3 (C-4), 113.2 (C-2), 105.0 (C-21), 99.1 (C21′), 55.7 (OMe), 55.5 (OMe), 55.2 (OMe). Anal. Calc. for C28H23O4N C, 76.87; H, 5.30; N, 3.20. Found C, 74.15; H, 5.41; N, 3.15.
1,3-Bis(4-chlorophenyl)acridin-9(10H)-one (3o). Prepared from compound 2o (30 mg, 0.07 mol); Yield: 13 mg (0.03 mmol, 43% yield). Orange solid Mp 298 °C. IR νmax (film): 3264, 3114, 2922, 2105, 1619. 1H-NMR (300 MHz, DMSO-d6) δ 11.84 (s, 1H), 8.04 (dd, J = 8.2, 1.6 Hz, 1H), 7.87–7.81 (m, 2H), 7.78 (d, J = 1.8 Hz, 1H), 7.72 (ddd, J = 8.5, 6.9, 1.6 Hz, 1H), 7.63–7.58 (m, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.45–7.34 (m, 4H), 7.26–7.18 (m, 2H). 13C-NMR (75 MHz, DMSO-d6) δ 176.8 (CO), 143.3 (C-5), 142.7 (C-3), 142.4 (C-7), 140.9 (C-19), 137.9 (C-15), 134.1 (C-1), 133.9 (C-9), 131.7 (C-18), 131.6 (C-22), 130.9 (C-17), 130.1 (C-21), 129.7 (C-16), 129.4 (C-20), 127.5 (C-11), 126.7 (C-14), 123.3 (C-10), 122.4 (C-12), 117.4 (C-8), 117.0 (C-4), 115.3 (C-2). Anal. Calc. for C25H15ONCl2 C, 72.13; H, 3.63; N, 3.36. Found C, 71.23; H, 3.76; N, 3.53.

4. Conclusions

The atom-economic method described here achieves the transformation of very simple reagents and catalysts into derivatives of the 1,3-diaryl-9-acridone framework. The method allows the two-step synthesis of dihydroacridone derivatives 2 having some potential significance as fluorescent probes for oxidant species, including reactive oxygen species (ROS) and reactive nitrogen species (NOS), since the absence of the C1-C2 double bond prevents the full conjugation of their two potential fluorescent chromophores, namely the m-terphenyl and acridone fragments, which would be restored upon dehydrogenation. This is an aspect of the chemistry of our compounds that will be studied in the near future. On the other hand, exposure of compounds 2 to nitrobenzene under microwave irradiation allowed their dehydrogenation to the fully aromatic derivatives 3, which have a high potential biological significance. By forming two rings, one carbon-nitrogen and three carbon-carbon bonds over two steps, our work demonstrates the high significance of multicomponent reactions followed by suitable postcondensation modifications in terms of the generation of structural diversity.

Supplementary Materials

The following are available online, copies of NMR spectra of new compounds.

Author Contributions

Conceptualization, J.F.G. and J.C.M.; methodology, D.R. and J.G.-C.; writing—original draft preparation, D.R., J.G.-C., J.F.G. and J.C.M.; writing—review and editing, D.R., J.G.-C., J.F.G. and J.C.M.; supervision, J.F.G. and J.C.M.; funding acquisition, J.C.M. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by MICINN (grant RTI2018-097662-B-I00, to J.C.M.) and Santander-UCM (grant PR87/19-22691, to J.F.G.). The APC received no funding.

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Molecules 25 05565 g001 550
Figure 1. Selected bioactive 9-acridones.
Figure 1. Selected bioactive 9-acridones.
Molecules 25 05565 g001
Molecules 25 05565 sch001 550
Scheme 1. Main reported synthetic approaches to acridin-9-ones. Methods based on: (a) Jourdan-Ullmann coupling; (b) reactions of anthranilic esters with arynes; (c) iodine-promoted oxidative cyclizations; (d) oxidative cyclizations of o-arylamino benzophenones.
Scheme 1. Main reported synthetic approaches to acridin-9-ones. Methods based on: (a) Jourdan-Ullmann coupling; (b) reactions of anthranilic esters with arynes; (c) iodine-promoted oxidative cyclizations; (d) oxidative cyclizations of o-arylamino benzophenones.
Molecules 25 05565 sch001
Molecules 25 05565 sch002 550
Scheme 2. Our planned route to 1,3-diarylacridin-9-ones.
Scheme 2. Our planned route to 1,3-diarylacridin-9-ones.
Molecules 25 05565 sch002
Molecules 25 05565 sch003 550
Scheme 3. Three-component synthesis of dihydroterphenyl derivatives 1 from chalcones, anilines and β-ketoesters.
Scheme 3. Three-component synthesis of dihydroterphenyl derivatives 1 from chalcones, anilines and β-ketoesters.
Molecules 25 05565 sch003
Molecules 25 05565 sch004 550
Scheme 4. Microwave-assisted cyclization of m-terphenyl-derived aminoesters 1 to 1,3-diaryl-1,2-dihydroacridin-9(10H)-ones 2.
Scheme 4. Microwave-assisted cyclization of m-terphenyl-derived aminoesters 1 to 1,3-diaryl-1,2-dihydroacridin-9(10H)-ones 2.
Molecules 25 05565 sch004
Molecules 25 05565 sch005 550
Scheme 5. Aromatization of compounds 2, with nitrobenzene having the dual role of solvent and oxidizing reagent.
Scheme 5. Aromatization of compounds 2, with nitrobenzene having the dual role of solvent and oxidizing reagent.
Molecules 25 05565 sch005
Molecules 25 05565 sch006 550
Scheme 6. A summary of bond formation in our synthetic pathway.
Scheme 6. A summary of bond formation in our synthetic pathway.
Molecules 25 05565 sch006
Table
Table 1. Results of the multicomponent reaction leading to dihydroterphenyl derivatives 1.
Table 1. Results of the multicomponent reaction leading to dihydroterphenyl derivatives 1.
CompoundAr1Ar2R 1Yield, % 1
1aPhPhH83
1bPhPh4-NMe290
1cPhPh4-F77
1dPhPh4-Cl75
1ePhPh4-Br72
1fPhPh3,5-Cl254
1gPhPh3,5-Me290
1hPh4-NO2C6H4H82
1i4-BrC6H4PhH80
1j Molecules 25 05565 i001PhH85
1k Molecules 25 05565 i002 Molecules 25 05565 i003H81
1l4-MeOC6H4PhH84
1m4-ClC6H4PhH76
1n2,4-(MeO)2C6H44-MeOC6H4H69
1o4-ClC6H44-ClC6H4H59
1 Compounds 1a-1k have been previously described in reference 26.
Table
Table 2. Results of the synthesis of 1,3-diaryl-1,2-dihydroacridin-9(10H)-one derivatives 2.
Table 2. Results of the synthesis of 1,3-diaryl-1,2-dihydroacridin-9(10H)-one derivatives 2.
CompoundAr1Ar2RYield, % 1
2aPhPhH94
2bPhPh7-NMe296
2cPhPh7-F86
2dPhPh7-Cl75
2ePhPh7-Br77
2fPhPh6,8-Cl283
2gPhPh6,8-Me282
2hPh4-NO2C6H4H0 1
2i4-BrC6H4PhH95
2j Molecules 25 05565 i004PhH94
2k Molecules 25 05565 i005 Molecules 25 05565 i006H92
2l4-MeOC6H4PhH77
2m4-ClC6H4PhH86
2n2,4-(MeO)2C6H34-MeOC6H4H85
2o4-ClC6H44-ClC6H4H42
1 Compound 2h was aromatized to 3h under the reaction conditions in 86% overall yield.
Table
Table 3. Results of the aromatization of compounds 2.
Table 3. Results of the aromatization of compounds 2.
CompoundAr1Ar2ROxidantYield, %
3aPhPhHPd/C0
MnO0
NBS0
DDQ56
C6H5NO282
3bPhPh7-NMe2C6H5NO280
3cPhPh7-FC6H5NO285
3dPhPh7-ClC6H5NO278
3ePhPh7-BrC6H5NO280
3fPhPh6,8-Cl2C6H5NO278
3gPhPh6,8-Me2C6H5NO276
3hPh4-NO2C6H4HC6H5NO286 1
3i4-BrC6H4PhHC6H5NO279
3j Molecules 25 05565 i007PhHC6H5NO284
3k Molecules 25 05565 i008 Molecules 25 05565 i009HC6H5NO277
3l4-MeOC6H4PhHC6H5NO274
3m4-ClC6H4PhHC6H5NO270
3n2,4-(MeO)2C6H34-MeOC6H4HC6H5NO277
3o4-ClC6H44-ClC6H4HC6H5NO243
1 Compound 3h was obtained directly from 1h, without isolation of 2h.
Sample Availability: Not available.
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Rocchi, D.; Gómez-Carpintero, J.; González, J.F.; Menéndez, J.C. Sustainable Access to Acridin-9-(10H)ones with an Embedded m-Terphenyl Moiety Based on a Three-Component Reaction. Molecules 2020, 25, 5565. https://doi.org/10.3390/molecules25235565

AMA Style

Rocchi D, Gómez-Carpintero J, González JF, Menéndez JC. Sustainable Access to Acridin-9-(10H)ones with an Embedded m-Terphenyl Moiety Based on a Three-Component Reaction. Molecules. 2020; 25(23):5565. https://doi.org/10.3390/molecules25235565

Chicago/Turabian Style

Rocchi, Damiano, Jorge Gómez-Carpintero, Juan F. González, and J. Carlos Menéndez. 2020. "Sustainable Access to Acridin-9-(10H)ones with an Embedded m-Terphenyl Moiety Based on a Three-Component Reaction" Molecules 25, no. 23: 5565. https://doi.org/10.3390/molecules25235565

APA Style

Rocchi, D., Gómez-Carpintero, J., González, J. F., & Menéndez, J. C. (2020). Sustainable Access to Acridin-9-(10H)ones with an Embedded m-Terphenyl Moiety Based on a Three-Component Reaction. Molecules, 25(23), 5565. https://doi.org/10.3390/molecules25235565

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