Expedient synthesis of 1,2,4-triazinyl substituted benzo[c]coumarins via double oxidation strategy published by Ural Federal University eISSN 2411-1414 chimicatechnoacta.ru ARTICLE 2023, vol. 10(2), No. 202310205 DOI: 10.15826/chimtech.2023.10.2.05 1 of 7 Expedient synthesis of 1,2,4-triazinyl substituted benzo[c]coumarins via double oxidation strategy Ramil F. Fatykhov a * , Igor A. Khalymbadzha a , Ainur D. Sharapov a, Anastasia P. Potapova a, Ekaterina S. Starnovskaya ab , Dmitry S. Kopchuk ab , Oleg N. Chupakhin ab a: Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia b: Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620219, Russia * Corresponding author: rf.fatykhov@urfu.ru This paper belongs to a Regular Issue. Abstract Herein, we report a convenient one-pot synthesis of 1,2,4-triazinyl deriv- atives of benzocoumarins. The proposed approach consists of the nucleo- philic addition of tetrahydrobenzo annulated dimethoxycoumarin to 1,2,4- triazines followed by double oxidation of both dihydrotriazine and tetra- hydrobenzo groups with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The nucleophilic addition of the dimethoxycoumarin to 1,2,4-tria- zines was carried out in the presence of three-fold excess of methanesul- fonic acid in DCM at room temperature. It takes place between positions 8 and 5 of coumarin and 1,2,4-triazine, respectively. The double oxidation step was carried out with 3.6 equivalent of DDQ. Selective oxidation of dihy- drotriazine moiety, without affecting the tetrahydrobenzo fragment, was achieved using 1.2 equivalent of tetrachlorobenzoquinone (TCQ). The differ- ences in the oxidation with TCQ and DDQ appear to be related to the higher oxidative potential of DDQ in contrast to TCQ. The advantages of the method are the elimination of the use of transition metals, the availability of starting materials, and the simplicity of the procedure. The proposed approach pro- vides a two-step one-pot protocol for the synthesis of triazinyl benzocouma- rins, precursors for the preparation of push-pull pyridinyl chromophore. Keywords coumarin 1,2,4-triazine nucleophilic substitution of hydrogen quinone oxidation push-pull chromophore Received: 06.03.23 Revised: 27.03.23 Accepted: 04.04.23 Available online: 11.04.23 Key findings ● One-pot synthesis of triazinyl-benzo[c]coumarin conjugate was developed. ● Oxidation of adduct with DDQ leads to double oxidation of both dihydrotriazine and tetrahydrobenzo groups. ● Oxidation of adduct with TCQ leads to chemoselective oxidation of dihydrotriazine. © 2023, the Authors. This article is published in open access under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 1. Introduction Azaheterocyclic coumarin derivatives provide one of most important photophysical-active compounds [1–3]. Due to good photophysical properties, such as high quantum yields and long-wavelength absorption/emission, various push-pull coumarins, containing azaheterocyclic fragment, have been studied as sensors [3–5] and fluorescent probes [6–8], com- ponents of organic light-emitting diodes (OLED) [9, 10] and solar cells [11, 12]. For example, coumarin-based terpyri- dine–zinc complex (Figure 1) demonstrated sensing ability for pyrophosphate (PPi) in aqueous media and was success- fully applied to fluorescence imaging for PPi in Hi-5 cells and Caenorhabditis elegans [13]. Coumarin-based cyclometalated Ir(III) complex (Figure 1) was studied as an emitter in OLED, and the device based on this derivative displayed impressive electroluminescence performance [14]. Coumarin–benzothi- azole–chlorambucil conjugate (Figure 1) was developed as a pH-sensitive photoresponsive drug delivery system [15]. In the literature, the synthesis of azinyl-coumarin or benzo- coumarin derivatives is reported by multistep reactions se- quences, involving construction of azaheterocyclic ring (Scheme 1, a) [16] or pyrone core (Scheme 1, b) [17] from corresponding precursors or transition metal (TM)-catalyzed cross-coupling re- actions between prefunctionalized precursors (Scheme 1, c) [14]. http://chimicatechnoacta.ru/ https://doi.org/10.15826/chimtech.2023.10.2.05 mailto:rf.fatykhov@urfu.ru http://creativecommons.org/licenses/by/4.0/ https://orcid.org/0000-0003-3129-8658 https://orcid.org/0000-0002-8043-8023 https://orcid.org/0000-0002-9679-8269 https://orcid.org/0000-0002-0397-4033 https://orcid.org/0000-0002-1672-2476 https://crossmark.crossref.org/dialog/?doi=https://doi.org/10.15826/chimtech.2023.10.2.05&domain=pdf&date_stamp=2023-04-11 https://journals.urfu.ru/index.php/chimtech/rt/suppFiles/6627/0 Chimica Techno Acta 2023, vol. 10(2), No. 202310205 ARTICLE 2 of 7 DOI: 10.15826/chimtech.2023.10.2.05 Figure 1 Some important azaheterocyclic coumarin derivatives. Scheme 1 Approaches to azinyl-coumarin. Nucleophilic substitution of hydrogen (SNH) [18] in ni- trogen-containing heterocycles represents a powerful tool for the construction of a novel C–C bond, conforming to the requirements of “green” chemistry and PASE (pot, atom, step economy) approaches. The advantages of this ap- proach are the avoidance of TM catalysts and the so-called “chlorine technologies”, mild reaction conditions, which, in turn, leads to a decrease in the number of steps and an in- crease in the overall yield of the desired product. SNH reac- tions often proceed as the addition of a nucleophile to an electrophilic azine with the formation of a σН-adduct, which can subsequently be oxidized in the presence of an external oxidizing agent (air oxygen [19], 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (DDQ) [20–23], K3[Fe(CN)6] [24–26], MnO2 [22, 27]) to a product of nucleophilic substitution of hydrogen. Earlier, we proposed a convenient synthetic approach to push-pull 8-pyridinylcoumarin chromophores (Scheme 1, d) by using a sequence of reactions of nucleophilic substi- tution of hydrogen and Boger pyridine synthesis in the series of 3,6-diaryl-substituted 1,2,4-triazines and 5,7-di- methoxycoumarins [20, 28]. Thus, at the first step, couma- rin was added to the triazine core with the formation of a 1,4-dihydrotriazine derivative, which then easily under- went aromatization under the action of the external oxidant such as DDQ with the formation of SNH product in high yield, which then transformed to pyridine derivative with 2,5-norbornadiene. In order to study the scope and limita- tions of this SNH approach, we adopted synthetic protocol of the oxidative cross-coupling of 1,3-dimethoxy-7,8,9,10-tet- rahydro-6H-benzo[c]coumarin 1 with 3,6-substituted tria- zines 2. In the present work, we report the double aromati- zation of both the dihydrotriazine and tetrahydrobenzene moieties (Scheme 1, e). This double aromatization strategy allowed us to extend the opportunities of SNH reactions in triazines providing stringboard access to 1,2,4-triazinyl substituted benzo[c]coumarins. 2. Experimental 1H NMR (400 MHz) and 13C NMR (101 MHz) spectra were recorded on a Bruker DRX-400 Avance spectrometer with DMSO-d6 or CDCl3 as a solvent at ambient temperature. Chemical shifts are reported in ppm and coupling constants are given in Hz. Data for 1H NMR are recorded as follows: chemical shift (ppm), multiplicity (s, singlet; d, doublet; t, triplet; m, multiplet; br s, broad signal), coupling constant (Hz), integration. High resolution mass spectra were rec- orded on an Agilent UHPLC/MS Accurate-Mass Q-TOF 1290/6545. Thin layer chromatography (TLC) was per- formed on silica gel coated glass slide (Merck, Silica gel G for TLC). Aluminium oxide 90 (70–230 mesh, Merck) was used for column chromatography. All solvents were dried and distilled before use. Commercially available substrates were freshly distilled before the reaction. Solvents, rea- gents and chemicals were purchased from Aldrich, Fluka, Merck, SRL, Spectrochem and Process Chemicals. All reac- tions involving moisture sensitive reactants were carried out using oven dried glassware. 2.1. 4-(3,6-Diphenyl-2,5-dihydro-1,2,4-triazin-5- yl)-1,3-dimethoxy-7,8,9,10-tetrahydro-6H- benzo[c]chromen-6-one 3a To a solution of coumarin 1 (260 mg, 1 mmol) and triazine 2a (233 mg, 1 mmol) in dichloromethane (DCM,6 ml) was added MeSO3H (288 mg, 3 mmol). The resulting solution was left for 3 h; the progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was washed with a saturated Na2CO3 solution. The organic layer was separated, dried with anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was recrystallized from benzene to give pure adduct 3a. White precipitate. Yield 449 mg (91%). 1H NMR (400 MHz, DMSO-d6) δ 11.14–10.93 (br s, 1H), 7.86– 7.77 (m, 2H), 7.67–7.58 (m, 2H), 7.47–7.35 (m, 3H), 7.30– 7.20 (m, 3H), 6.57 (s, 1H), 6.41 (s, 1H), 3.92 (s, 3H), https://doi.org/10.15826/chimtech.2023.10.2.05 https://doi.org/10.15826/chimtech.2023.10.2.05 Chimica Techno Acta 2023, vol. 10(2), No. 202310205 ARTICLE 3 of 7 DOI: 10.15826/chimtech.2023.10.2.05 3.85 (s, 3H), 2.97–2.85 (m, 2H), 2.42–2.29 (m, 2H), 1.67– 1.54 (m, 4H). 13C NMR (101 MHz, DMSO-d6) δ 159.8, 159.2, 158.1, 151.7, 149.3, 149.2, 139.3, 136.0, 133.4, 130.1, 128.6, 128.2, 128.1, 126.2, 124.9, 118.0, 111.2, 103.9, 92.7, 56.3, 56.1, 45.8, 29.4, 24.2, 21.7, 20.6. HRMS (ESI): C30H28N3O4+ [(M+H)+]: calcd.: 494.2074; found: 494.2069. 2.2. 4-(3,6-Diphenyl-1,2,4-triazin-5-yl)-1,3-di- methoxy-7,8,9,10-tetrahydro-6H- benzo[c]chromen-6-one 4a Dihydrotriazine 3a (493 mg, 1 mmol) was dissolved in 1,2- dichloroethane (DCE, 10 ml), tetrachloro-1,4-benzoquinone (TCQ) (340 mg, 1.2 mmol) was added, and the mixture was refluxed for 6 h. The solvent was removed under reduced pressure, and the residue was recrystallized from butanol-1 to give pure 4a. Pale yellow precipitate. Yield 417 mg, 85%. 1H NMR (400 MHz, CDCl3) δ 8.60–8.54 (m, 2Н), 7.58–7.49 (m, 5Н), 7.35–7.27 (m, 3Н), 6.21 (s, 1H), 3.90 (s, 3Н), 3.51 (s, 3Н), 3.11–3.10 (m, 2Н), 2.57–2.46 (m, 2Н), 1.80–1.69 (m, 4Н). 13C NMR (101 MHz, CDCl3) δ 162.3, 160.8, 160.3, 158.4, 152.4, 152.3, 149.3, 135.9, 135.3, 131.4, 129.3, 128.8, 128.6, 128.5, 128.2, 120.2, 107.2, 105.5, 91.2, 66.0, 55.8, 30.1, 24.8, 22.5, 21.4. HRMS (ESI): C30H26N3O4+ [(M+H)+]: calcd.: 492.1918; found: 492.1923. 2.3. General method for synthesis of compounds 5 To a solution of coumarin 1 (260 mg, 1 mmol) and corre- sponding triazine 2a–i (1 mmol) in DCM (6 ml) was added MeSO3H (288 mg, 3 mmol). The resulting solution was left for 3 h. After completion of the reaction, the reaction mix- ture was washed with a saturated Na2CO3 solution. The or- ganic layer was separated, dried with anhydrous sodium sulfate, and the solvent was removed under reduced pres- sure to give adduct 3, which then was dissolved in DCE (10 ml). Then, DDQ (3.6 mmol, 817 mg) was added, and the mixture was refluxed for 6 h. The resulting mixture was purified using flash chromatography (Al2O3/ethyl acetate). The solvent was removed under reduced pressure, and the residue was recrystallized from butanol-1 to give pure 5. 2.3.1. 4-(3,6-Diphenyl-1,2,4-triazin-5-yl)-1,3-dimethoxy- 6H-benzo[c]chromen-6-one 5a Yellow powder. Yield 429 mg, 88%; 1H NMR (400 MHz, CDCl3) δ 8.89 (d, J = 8.4 Hz, 1H), 8.64–8.57 (m, 2H), 8.34 (d, J = 7.9 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.61– 7.56 (m, 2H), 7.55–7.46 (m, 4H), 7.34–7.27 (m, 3H), 4.08 (s, 3H), 3.60 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.3, 160.7, 160.4, 158.4, 158.3, 152.4, 151.2, 135.9, 135.3, 135.0, 134.6, 131.4, 130.4, 129.3, 128.9, 128.6, 128.5, 128.2, 127.6, 126.7, 119.9, 108.0, 102.5, 91.8, 56.2, 56.0. HRMS (ESI): C30H22N3O4+ [(M+H)+]: calcd.: 488.1605; found: 488.1609. 2.3.2. 4-(3,6-bis(4-Methoxyphenyl)-1,2,4-triazin-5-yl)- 1,3-dimethoxy-6H-benzo[c]chromen-6-one 5b Yellow powder. Yield 421 mg, 77%. 1H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 8.5 Hz, 1H), 8.58–8.51 (m, 2H), 8.33 (dd, J = 7.5, 1.6 Hz, 1H), 7.75 (ddd, J = 8.5, 7.5, 1.6 Hz, 1H), 7.56–7.43 (m, 3H), 7.06–6.98 (m, 2H), 6.85–6.75 (m, 2H), 6.41 (s, 1H), 4.08 (s, 3H), 3.87 (s, 3H), 3.75 (s, 3H), 3.63 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.4, 161.6, 160.6, 160.5 (2C), 158.3, 157.3, 152.0, 151.1, 135.0, 134.6, 130.4, 130.2, 129.8, 128.4, 128.0, 127.5, 126.7, 119.9, 114.2, 113.7, 108.3, 102.4, 91.9, 56.2, 56.1, 55.5, 55.3. HRMS (ESI): C32H26N3O6+ [(M+H)+]: calcd.: 548.1816; found: 548.1820. 2.3.3. 1,3-Dimethoxy-4-(6-(4-methoxyphenyl)-3-(p-tolyl)- 1,2,4-triazin-5-yl)-6H-benzo[c]chromen-6-one 5c Yellow powder. Yield 405 mg, 74%. 1H NMR (400 MHz, CDCl3) δ 8.87 (d, J = 8.4 Hz, 1H), 8.48 (d, J = 7.9 Hz, 2H), 8.32 (d, J = 7.9 Hz, 1H), 7.74 (t, J = 7.9 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.47 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 7.9 Hz, 2H), 6.78 (d, J = 8.4 Hz, 2H), 6.41 (s, 1H), 4.07 (s, 3H), 3.74 (s, 3H), 3.62 (s, 3H), 2.42 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 161.9, 160.6, 160.5, 160.4, 158.3, 157.7, 152.1, 151.1, 141.6, 134.9, 134.6, 132.6, 130.3, 129.8, 129.6, 128.4, 128.3, 127.5, 126.7, 119.8, 113.7, 108.2, 102.4, 91.9, 56.2, 56.0, 55.3, 21.7. HRMS (ESI): C32H26N3O5+ [(M+H)+]: calcd.: 532.1867; found: 532.1871. 2.3.4. 1,3-Dimethoxy-4-(3-phenyl-6-(p-tolyl)-1,2,4-tria- zin-5-yl)-6H-benzo[c]chromen-6-one 5d Yellow powder. Yield 296 mg, 59%. 1H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 8.5 Hz, 1H), 8.64–8.55 (m, 2H), 8.34 (dd, J = 7.9, 1.6 Hz, 1H), 7.76 (ddd, J = 8.5, 7.9, 1.6 Hz, 1H), 7.56–7.44 (m, 6H), 7.11–7.04 (m, 2H), 6.41 (s, 1H), 4.08 (s, 3H), 3.61 (s, 3H), 2.28 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.0, 160.7, 160.4, 158.3, 152.3, 151.2, 134.9, 135.4, 135.0, 134.6, 132.9, 131.3, 130.4, 129.0, 128.8, 128.6, 128.4, 128.4, 127.5, 126.7, 119.9, 108.2, 102.4, 91.9, 56.2, 56.0, 21.5. HRMS (ESI): C32H26N3O5: calcd.: 532.1867; found: 532.1871. 2.3.5. 1,3-Dimethoxy-4-(6-(naphthalen-2-yl)-3-phenyl- 1,2,4-triazin-5-yl)-6H-benzo[c]chromen-6-one 5e Yellow powder. Yield 381 mg, 71%. 1H NMR (400 MHz, CDCl3) δ 8.86 (d, J = 8.5 Hz, 1H), 8.69–8.60 (m, 2H), 8.33 (dd, J = 7.9, 1.6 Hz, 1H), 8.15 (s, 1H), 7.80–7.71 (m, 4H), 7.67 (dd, J = 8.5, 1.6 Hz, 1H), 7.60–7.50 (m, 3H), 7.51–7.38 (m, 3H), 6.34 (s, 1H), 4.03 (s, 3H), 3.54 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.2, 160.7, 160.5, 158.4, 158.3, 152.6, 151.3, 135.3, 135.0, 134.6, 133.6, 133.3, 133.0, 131.4, 130.4, 128.9, 128.8, 128.6, 128.5, 127.9, 127.7, 127.6, 126.9, 126.7, 126.3, 125.6, 119.8, 108.0, 102.5, 91.8, 56.2, 56.0. HRMS (ESI): C34H24N3O4+ [(M+H)+]: calcd.: 538.1761; found: 538.1757. 2.3.6. 4-(6-(4-Bromophenyl)-3-phenyl-1,2,4-triazin-5- yl)-1,3-dimethoxy-6H-benzo[c]chromen-6-one 5f Yellow powder. Yield 441 mg, 78%. 1H NMR (400 MHz, CDCl3) δ 8.89 (d, J = 8.5 Hz, 1H), 8.63–8.56 (m, 2H), 8.34 (dd, J = 7.5, 1.6 Hz, 1H), 7.77 (ddd, J = 8.5, 7.5, 1.6 Hz, 1H), 7.61–7.44 (m, 6H), 7.44–7.37 (m, 2H), 6.41 (s, 1H), 4.10 (s, 3H), 3.64 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.5, 160.9, 160.3, 158.2, 157.5, 152.3, 151.1, 135.1, 135.1, 134.9, 134.5, 131.6, 131.5, 130.4, 130.0, 128.9, 128.7, 127.7, 126.7, https://doi.org/10.15826/chimtech.2023.10.2.05 https://doi.org/10.15826/chimtech.2023.10.2.05 Chimica Techno Acta 2023, vol. 10(2), No. 202310205 ARTICLE 4 of 7 DOI: 10.15826/chimtech.2023.10.2.05 124.0, 119.8, 107.5, 102.5, 91.8, 56.3, 56.0. HRMS (ESI): C30H21BrN3O4+ [(M+H)+]: calcd.: 566.0710; found: 566.0715. 2.3.7. 4-(6-(4-Bromophenyl)-3-(4-methoxyphenyl)- 1,2,4-triazin-5-yl)-1,3-dimethoxy-6H- benzo[c]chromen-6-one 5g Yellow powder. Yield 446 mg, 75%. 1H NMR (400 MHz, CDCl3) δ 8.89 (d, J = 8.5 Hz, 1H), 8.59–8.51 (m, 2H), 8.34 (dd, J = 7.5, 1.6 Hz, 1H), 7.77 (ddd, J = 8.5, 7.5, 1.6 Hz, 1H), 7.54–7.38 (m, 4H), 7.07–6.98 (m, 2H), 6.41 (s, 1H), 4.10 (s, 3H), 3.88 (s, 3H), 3.63 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.6, 162.2, 160.8, 160.4, 158.2, 156.8, 152.1, 151.2, 135.1, 134.5, 131.5, 130.4, 130.4, 130.0, 127.7, 127.7, 126.7, 123.8, 119.8, 114.3 (2C), 107.7, 102.5, 91.8, 56.3, 56.0, 55.5. HRMS (ESI): C31H23BrN3O5+ [(M+H)+]: calcd.: 596.0816; found: 596.0822. 2.3.8. 4-(6-(4-Bromophenyl)-3-(p-tolyl)-1,2,4-triazin-5- yl)-1,3-dimethoxy-6H-benzo[c]chromen-6-one 5h Yellow powder. Yield 428 mg, 74%. 1H NMR (400 MHz, CDCl3) δ 8.89 (d, J = 8.5 Hz, 1H), 8.49 (d, J = 8.0 Hz, 2H), 8.34 (dd, J = 7.9, 1.6 Hz, 1H), 7.77 (ddd, J = 8.5, 7.9, 1.6 Hz, 1H), 7.54–7.38 (m, 5H), 7.33 (d, J = 8.0 Hz, 2H), 6.41 (s, 1H), 4.10 (s, 3H), 3.64 (s, 3H), 2.44 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 162.5, 160.8, 160.3, 158.2, 157.3, 152.2, 151.1, 142.0, 135.1, 135.0, 134.5, 132.4, 131.5, 130.4, 130.0, 129.7, 128.6, 127.7, 126.7, 123.9, 119.8, 107.6, 102.5, 91.8, 56.2, 56.0, 21.7. HRMS (ESI): C31H23BrN3O4+ [(M+H)+]: calcd.: 580.0866; found: 580.0870. 2.3.9. 1,3-Dimethoxy-4-(3-phenyl-1,2,4-triazin-5-yl)-6H- benzo[c]chromen-6-one 5i Yellow powder. Yield 275 mg, 67%. 1H NMR (400 MHz, DMSO-d6) δ 9.53 (s, 1H), 8.96–8.90 (m, 1H), 8.50–8.43 (m, 2H), 8.26–8.19 (m, 1H), 7.93–7.88 (m, 1H), 7.68–7.56 (m, 4H), 6.92 (s, 1H), 4.19 (s, 3H), 3.96 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 162.8, 160.9, 159.5, 158.9, 153.7, 150.5, 150.3, 135.4, 134.8, 133.9, 131.8, 129.6, 129.1, 127.9, 127.8, 126.4, 119.0, 104.9, 101.1, 93.2, 56.8, 56.7. HRMS (ESI): C24H18BrN3O4+ [(M+H)+]: calcd.: 412.1292; found: 412.1297. 3. Results and Discussion We started our research with the reaction of dimethoxycou- marin 1 with 3,6-diphenyl-1,2,4-triazine 2a, which was car- ried out in the presence of three-fold excess of methanesul- fonic acid (MsOH) in DCM at room temperature, yielding dihydrotriazine 3a in high yield (Scheme 2), in accordance with the previously described procedure [2o]. Aromatization of the adduct 3a with 1.5 equivalent of DDQ (Table 1, entry 1) [20] provided a complex mixture of products. We hypothesized that, in contrast to our previous work [20, 28], DDQ not only oxidizes 1,4-dihydrotriazine core to give expected product of the nucleophilic substitu- tion of hydrogen 4a, but also aromatizes tetrahydrobenzene moiety yielding 5a and 6a, which is confirmed by the liter- ature data [29, 30]. However, it was found that increasing amount of oxi- dant up to 3.6 equivalents (1.2 equiv. per σ-bond) in 1,2- dichloroethane (DCE) at 70 °C allows producing 4-tria- zinyl-benzo[c]coumarin derivative 5a in 90% yield (Scheme 4). Further increasing of DDQ amount up to 5 equivalents did not improve the yield (Table 1, entry 3). In addition, we also demonstrated that using even four- fold excess of TCQ (Table 1, entry 4) instead of DDQ as the oxidizing agent in the same oxidation process led to aroma- tization of dihydrotriazine moiety with excellent chemose- lectivity to give SNH product (Scheme 5). After quick reoptimization of the reaction conditions, we found that the use of 1.2 eq. TCQ in DCE at 70 °C (Table 1, entry 5) could allow the formation of 4a in best yield. One can assume that the differences in the oxidation with TCQ and DDQ are related to the higher oxidative potential of DDQ in contrast to TCQ (0.51 vs. 0.01 volts [31]). Scheme 2 Synthesis of adduct 3a. Scheme 3 Formation of the complex mixture of products during the oxidation of adduct 3a with 1.5 equivalents of DDQ. Table 1 Optimization of the oxidation reaction conditions a. Entry Oxidant (equivalents) Product Yield b 1 DDQ (1.5 eq.) – c 2 DDQ (3.6 eq.) 5a 90 3 DDQ (5.0 eq.) 5a 88 4 TCQ (4.0 eq.) 4a 84 5 TCQ (1.2 eq.) 4a 85 6 air (bubbling) – d 7 oxygen (bubbling) – d 8 MnO2 (10 eq.) 4a 51 a Conditions: 3a (1 mmol), DCE (10 ml), 70°C; b Isolated yield; c Hard-to-separate mixture; d Starting material was isolated. https://doi.org/10.15826/chimtech.2023.10.2.05 https://doi.org/10.15826/chimtech.2023.10.2.05 Chimica Techno Acta 2023, vol. 10(2), No. 202310205 ARTICLE 5 of 7 DOI: 10.15826/chimtech.2023.10.2.05 Scheme 4 Oxidation of adduct 3a with 3.6 equivalents of DDQ. Scheme 5 Oxidation of adduct 3a with TCQ. Air or oxygen bubbling through the reaction mixture did not produce desired products (Table 1, entries 6 and 7, re- spectively), and only the starting material was isolated from the reaction mixture. Manganese oxide (IV) is another oxidizing agent that can oxidize dihydrotriazines to aromatic triazines [27]. When dihydrotriazine 3a was refluxed with 10 equivalents of MnO2 in dichloroethane, product 4a was formed in 51% yield (Table 1, entry 8). Formation of compound 5a was proven by 1H and 13C NMR spectroscopy data. In particular, multipletes of pro- tons of the methylene groups were not observed in the 3.5– 1.5 ppm region. In addition, signals of sp3-hybridized car- bons of the tetrahydrobenzene ring were also absent in the high field of 13C NMR spectrum. After optimizing the reaction conditions, we examined the applicability and scope of this reaction sequence with re- spect to 3,6-diaryl-substituted 1,2,4-triazines 2a–h. The re- sults are summarized in Scheme 6. 1,2,4-Triazines 2 bearing p-tolyl, 4-methoxyphenyl (PMP), 4-bromophenyl and even bulky naphthalenyl group at the C6 position were tolerated, and corresponding products 5a–h were isolated in 59–88% yields after recrystallization. The reduced yield for com- pound 5d may be due to oxidation of the p-tolyl group with DDQ [32]. On the other hand, all attempts to involve 3-pyri- din-2-yl substituted 1,2,4-triazines in this reaction sequence were unsuccessful. In addition, using 3-phenyl-1,2,4-triaiz- ine 2i also provided desired product 5i in good yield. It is well known that 1,2,4-triazines are readily accessi- ble and cheap building block for construction of pyridine derivatives, which are used as functional materials [33]. At the same time, the annulation of an additional benzene cy- cle to the coumarin framework often improves the photo- physical characteristics: it leads to a bathochromic shift of the absorption and emission maxima and can also increase the fluorescence quantum yield [34, 35]. Scheme 6 Synthesis of benzo[c]coumarin 5. Thus, the obtained products may be considered as pre- cursors for pyridyl-coumarin conjugate chromophores. Fur- ther transformations and detailed photophysical studies are in progress and will be published later. 4. Limitations We proposed the method of synthesis of 1,2,4-triazinyl sub- stituted benzo[c]coumarins via double aromatization strat- egy. Various 3,6-biaryl-1,2,4-triazines were involved in this transformation. However, in the case of 3-pyridinyl substi- tuted 1,2,4-triaines, desired benzo[c]coumarin derivatives were not observed. In the course of our further research, we will attempt to overcome those limitations and develop a method of the oxidative cross-coupling 3-pyridin-2-yl 1,2,4-triazines with coumarins. 5. Conclusion We proposed a new protocol of the synthesis of triazinyl- benzo[c]coumarin derivatives by means of simultaneous oxidation dihydrotriazine and tetrahydrobenzene frame- works under the action of DDQ as an oxidant. In contrast to DDQ, oxidation in the presence of TCQ exclusively provided the SNH products. The obtained products could serve as pre- cursors for push-pull pyridyl-coumarin conjugate chromo- phores for potential applications in material science. ● Supplementary materials This manuscript contains supplementary materials, which are available on the corresponding online page. https://doi.org/10.15826/chimtech.2023.10.2.05 https://doi.org/10.15826/chimtech.2023.10.2.05 Chimica Techno Acta 2023, vol. 10(2), No. 202310205 ARTICLE 6 of 7 DOI: 10.15826/chimtech.2023.10.2.05 ● Funding This work was supported by the Russian Science Founda- tion (grant no. 21-73-00214). ● Acknowledgments None. ● Author contributions Conceptualization: R.F.F., I.A.K. Data curation: R.F.F. Formal Analysis: A.D.S, E.S.S., A.P.P. Funding acquisition: R.F.F. Investigation: E.S.S., A.P.P. Methodology: A.D.S, E.S.S., D.S.K. Project administration: R.F.F. Resources: A.D.S., A.P.P., D.S.K. Software: R.F.F. Supervision: O.N.C. Validation: R.F.F., D.S.K. Visualization: I.A.K. 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