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DOI: 10.1055/s-0043-1775495
Visible-Light-Induced Methylation of Quinoxalin-2(1H)-ones Catalyzed by Dye Molecules
We sincerely thank the Natural Science Foundation of Liaoning Province (LJ212410149027), Liaoning Revitalization Talents Program (XLYC1902085), and China Petrochemical Corporation Innovation Project (223020) for financial support.
Abstract
A visible-light-driven, molecular dye-catalyzed C-3 methylation strategy for quinoxalin-2(1H)-ones has been successfully developed. The methodology demonstrates broad substrate compatibility with various substituted quinoxalin-2(1H)-ones, which could react with N,N,N′,N′,N′′-pentamethyldiethylenetriamine (PMDETA) efficiently at room temperature under ambient atmospheric conditions to afford the corresponding 3-methylquinoxalinone derivatives in moderate to good yields. It is noteworthy that this protocol offers a simple, clean, and transition-metal-free approach, establishing a practical and eco-friendly methodology for constructing diverse C3-methylated quinoxalinone scaffolds, complementing existing synthetic strategies for site-selective functionalization of these heterocycles.
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Quinoxalin-2(1H)-ones represent an important class of nitrogen-containing heterocyclic compounds found in numerous biologically active natural products[1] and pharmaceuticals.[2] Particularly, C3-methyl-substituted quinoxalin-2(1H)-ones[3] have attracted considerable attention due to their remarkable biological activities (Scheme [1]).[4] Conventionally, 3-alkylquinoxalin-2(1H)-ones are synthesized through multistep procedures involving reactions between aryl-1,2-diamines[5] and alkyl-substituted keto acids or esters.[6] Recently, direct C3–H alkylation of quinoxalin-2(1H)-ones by radical processes has developed as a powerful strategy for constructing diverse 3-alkylquinoxalin-2(1H)-ones, including both thermal synthesis[7] and photocatalytic approaches.[8]
In 2021, L. Yang and co-workers[9] reported a metal- and oxidant-free protocol for efficient construction of 3-alkylquinoxalinones through base-promoted direct alkylation of quinoxalin-2(1H)-ones with phosphonium ylides, achieving good to excellent yields (Scheme [1a]). Subsequently in 2022, Wu’s group[10] developed a metal-free method utilizing aryl alkyl ketones as alkylating reagents for quinoxalinone alkylation. This protocol demonstrated operational simplicity, broad substrate scope, and good functional group tolerance, significantly expanding the application potential of aryl alkyl ketones via C–C bond activation (Scheme [1b]). Compared with thermal approaches, photocatalytic methods offer greener, more convenient, and environmentally friendly alternatives. In 2021, H. Yang’s group[11] established a mild, scalable, and practical protocol for direct C–H methylation of N-heteroarenes using N,N,N′,N′-tetramethylethylenediamine (TMEDA) as the methyl source (Scheme [1c]). Shen’s group[12] further advanced this field in 2022 by reporting a visible-light-induced decarboxylative alkylation of quinoxalin-2(1H)-ones with benziodoxolones using inexpensive catalytic CeCl3 as photocatalyst, expanding the application scope of metal salt photocatalysts (Scheme [1d]).
Photocatalysis,[13] as a green synthesis method, is an attractive strategy for the alkylation of quinoxalin-2(1H)-ones. However, these existing methods either require high reaction temperatures that increase energy consumption or necessitate additional additives when using transition metals or metal salts as photocatalysts.[14] Notably, successful applications of small-molecule dye photosensitizers – another important photocatalyst category in photocatalytic systems[15] – remain scarce for synthesizing 3-alkylquinoxalin-2(1H)-ones. To address this gap, we herein report a visible-light-initiated, small-molecule dye-catalyzed C-3 methylation reaction of quinoxalinones (Scheme [1e]). The successful implementation of this strategy broadens the synthetic approaches for visible-light-mediated preparation of 3-alkylquinoxalin-2(1H)-ones.
a Reaction conditions: 1a (0.05 mmol), base (0.1 mmol, 2.0 equiv), photocatalyst (1 mol%), solvent (0.5 mL), 30 W LED irradiation, under air, rt, 3.5 h.
b Yields determined by 1H NMR spectroscopy using toluene as an internal standard. N.R. = no reaction.
c PMDETA (1.5 equiv) was used.
d PMDETA (1.0 equiv) was used.
e AQ-2-COOH (0.5 mol%) was used.
f 1,4-Dioxane (0.3 mL) was used.
g 1,4-Dioxane (0.1 mL) was used.
To identify the optimal reaction conditions, N-methylquinoxalin-2(1H)-one (1a) was selected as the model substrate for reaction optimization (Table [1]). Initially, using 3-hydroxy-9H-xanthen-9-one (3-OH-XT) as the photocatalyst and 1,4-dioxane as the solvent, various methyl sources were screened (entries 1–5). We found that when N,N,N′,N′,N′′-pentamethyldiethylenetriamine (PMDETA) served as the methyl source, 1a was completely converted within 3.5 hours, affording the desired product 2a in 82% NMR yield. Subsequently, with a fixed reaction time of 3.5 hours, different organic dyes were evaluated as photocatalysts. Small-molecule organic photosensitizers such as rose bengal and others (entries 6–12) demonstrated unsatisfactory catalytic efficacy. When 9H-thioxanthen-9-one (TX) was used as the photosensitizer, the reaction achieved a yield of 83% (entry 13). The highest yield (86%) was achieved when anthraquinone-2-carboxylic acid (AQ-2-COOH) was employed as the photocatalyst (entry 14). Therefore, using PMDETA as the base and AQ-2-COOH as the photocatalyst, various solvents were screened (entries 15–27). The results demonstrated that 1,4-dioxane provided the best performance, suggesting that the solvent plays a crucial role in the reaction. Next, the amounts of base and photocatalyst were investigated (entries 28–30), revealing that 2 equivalents of base and 1 mol% of catalyst were optimal. Subsequently, investigation of the solvent volume effect on the reaction revealed that reduced solvent volume decreased the reaction yield (entries 31 and 32). Finally, control experiments were conducted, confirming the necessity of both the photocatalyst and light (entries 33 and 34). Thus, the conditions in entry 14 [AQ-2-COOH (1 mol%), PMDETA (2 equiv), 1,4-dioxane, purple LED, air (1 atm), room temperature] were considered as being the optimized conditions for further studies.
With the optimal conditions in hand, we explored the scope of C-3 methylation of quinoxalinones (Scheme [2]). The methylation of N-methylquinoxalin-2(1H)-one proceeded efficiently to afford 1,3-dimethylquinoxalin-2(1H)-one (2a) in 84% yield. Substituted derivatives demonstrated varied reactivity: 5-methyl-monosubstituted and 6,7-dimethyl-disubstituted analogues 2b and 2c were obtained in 69–78% yield, while the naphthyl derivative 2d was isolated in 61% yield. The 6,7-dichloro-disubstituted substrate exhibited good reactivity, yielding product 2e in 55%. The substrates bearing a halogen or nitrile group at the 6- or 7-position delivered the corresponding products 2f–2i in moderate yields. The scope of N-protecting groups was also investigated. N-Phenyl and N-benzyl group derivatives with methyl, tert-butyl, and halogen substituents consistently afforded products in good yields (2j–2o, 70–81%). However, the introduction of a trifluoromethyl group on the benzyl moiety resulted in diminished efficiency (2p, 45%). Notably, alternative N-alkyl groups, including linear and cyclic alkyl substituents, demonstrated moderate to good compatibility with the reaction system, yielding products 2q–2u in the 48–80% range. Significantly, the reaction exhibited broad functional group tolerance, successfully accommodating a terminal alkyne (2v, 77%) and olefin (2w, 71%). This versatility highlights the robustness of the methylation protocol across diverse substrate architectures.
Based on the above results and related literature,[14] a possible mechanism of visible-light-initiated, small-molecule dye-catalyzed C-3 methylation of quinoxalinones is proposed in Scheme [3]. Under irradiation with purple LED light, the photocatalyst (PC) is initially photoexcited to its excited state (PC*), which undergoes a single-electron transfer (SET) process with PMDETA to generate intermediate A and the radical anion PC •−. Subsequently, there is electron transfer from PC •− to molecular oxygen, thereby regenerating the ground-state photocatalyst while producing the superoxide anion radical (O2 •−). The O2 •− abstracts a proton from A, yielding B and hydroperoxyl radical (HOO•). B then reacts with substrate 1a to form 3, which undergoes an intramolecular 1,6-proton shift to generate 4. Subsequent isomerization of 4 produces 5. Notably, the protonated C–N bond in this intermediate may be weakened through protonation at the nitrogen atom, leading to bond cleavage and the formation of 6 and 7. A proton transfer between 6 and 7 generates 8 and 9. Finally, 9 reacts with HOO• to yield product 10, while 8 undergoes tautomerization to afford the target compound 2a.
In conclusion, we have developed a visible-light-induced, molecular dye-catalyzed C-3 methylation of quinoxalin-2(1H)-ones using PMDETA as the methyl source. The methodology demonstrates broad substrate universality and good functional group tolerance. The green and mild conditions showcase significant advantages in efficient construction of C3-methylated quinoxalinone derivatives. Particularly noteworthy is the atom-economical nature of this transformation, which enables the preparation of structurally diverse quinoxalinone scaffolds without requiring hazardous reagents or complex procedures, thereby establishing a green synthetic platform for methylation of quinoxalin-2(1H)-ones.
Unless otherwise stated, all reagents were purchased from commercial suppliers and used without further purification. All photocatalytic reactions were carried out using a purple LED (30 W) as the visible-light source at a distance of 8–10 cm at room temperature under an air atmosphere. Reactions were monitored by TLC (Yantai Jiangyou Silicone Development Co. silica gel HSGF254). Products were detected using a UV/vis lamp (254 nm). Column chromatography was performed on Qingdao Bay Fine Chemical Co. silica gel 60 (200–300 mesh). 1H (400 MHz) and 13C (100 MHz) NMR spectra of samples in CDCl3 at 298 K were recorded on an AVANCE III 400 spectrometer. The related substrates 1a–1w were synthesized according to literature reports.[16]
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3-Methylquinoxalin-2(1H)-ones 2; General Procedure
Quinoxalin-2(1H)-one 1 (0.5 mmol, 1 equiv), PMDETA (1 mmol, 2 equiv), AQ-2-COOH (1.3 mg, 1 mol%), and 1,4-dioxane (5.0 mL) were added to a 25-mL Schlenk bottle equipped with a magnetic stirrer. The mixture was irradiated by a purple LED at rt under air. The photoreaction was completed after 3.5 h, as monitored by TLC. The solvent was removed in vacuo and the residue was purified by flash column chromatography on silica gel (petroleum ether/ethyl acetate, 5:1 to 1:1) to afford 2.
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1,3-Dimethylquinoxalin-2(1H)-one (2a)[17]
Yellow solid; yield: 73.2 mg (84%).
1H NMR (400 MHz, CDCl3): δ = 7.80 (dd, J = 7.8, 1.4 Hz, 1 H), 7.57–7.47 (m, 1 H), 7.39–7.24 (m, 2 H), 3.71 (s, 3 H), 2.60 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.36, 155.16, 133.21, 132.62, 129.54, 129.41, 123.57, 113.57, 29.01, 21.60.
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1,3,5-Trimethylquinoxalin-2(1H)-one (2b)[18]
Yellow solid; yield: 73.4 mg (78%).
1H NMR (400 MHz, CDCl3): δ = 7.46–7.35 (t, J = 5.4 Hz, 1 H), 7.19 (d, J = 4.8 Hz, 1 H), 7.13 (d, J = 5.6 Hz, 1 H), 3.69 (s, 3 H), 2.68 (s, 3 H), 2.60 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.45, 155.10, 138.17, 133.25, 131.26, 129.14, 124.85, 111.47, 29.13, 21.82, 17.53.
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1,3,6,7-Tetramethylquinoxalin-2(1H)-one (2c)[19]
Yellow solid; yield: 69.8 mg (69%).
1H NMR (400 MHz, CDCl3): δ = 7.54 (s, 1 H), 7.05 (s, 1 H), 3.67 (s, 3 H), 2.57 (s, 3 H), 2.40 (s, 3 H), 2.34 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 156.98, 155.25, 139.19, 132.39, 131.20, 131.05, 129.52, 114.15, 28.91, 21.50, 20.43, 19.15.
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1,3-Dimethylbenzo[g]quinoxalin-2(1H)-one (2d)[19]
Yellow solid; yield: 68.4 mg (61%).
1H NMR (400 MHz, CDCl3): δ = 8.29 (s, 1 H), 7.93 (dd, J = 25.6, 5.6 Hz, 2 H), 7.61–7.53 (m, 2 H), 7.51–7.46 (t, J = 5.2 Hz, 1 H), 3.76 (s, 3 H), 2.64 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.95, 155.05, 133.29, 132.00, 131.90, 129.71, 128.40, 128.39, 127.64, 127.11, 125.23, 109.95, 29.03, 21.78.
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6,7-Dichloro-1,3-dimethylquinoxalin-2(1H)-one (2e)[17]
Yellow solid; yield: 66.9 mg (55%).
1H NMR (400 MHz, CDCl3): δ = 7.88 (s, 1 H), 7.38 (s, 1 H), 3.66 (s, 3 H), 2.58 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.99, 154.58, 133.59, 132.65, 131.73, 130.33, 127.33, 115.10, 29.30, 21.67.
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6-Chloro-1,3-dimethylquinoxalin-2(1H)-one (2f)[17]
Yellow solid; yield: 52.1 mg (50%).
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 2.4 Hz, 1 H), 7.47 (dd, J = 8.8, 2.4 Hz, 1 H), 7.22 (d, J = 8.8 Hz, 1 H), 3.68 (s, 3 H), 2.59 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.86, 154.81, 133.16, 131.92, 129.52, 128.85, 128.82, 114.70, 29.19, 21.67.
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7-Bromo-1,3-dimethylquinoxalin-2(1H)-one (2g)[19]
Yellow solid; yield: 63.3 mg (50%).
1H NMR (400 MHz, CDCl3): δ = 7.63 (d, J = 9.2 Hz, 1 H), 7.46–7.38 (m, 2 H), 3.66 (s, 3 H), 2.56 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.73, 154.77, 134.22, 131.43, 130.62, 126.77, 123.45, 116.60, 29.12, 21.58.
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7-Fluoro-1,3-dimethylquinoxalin-2(1H)-one (2h)[17]
White solid; yield: 48.9 mg (51%).
1H NMR (400 MHz, CDCl3): δ = 7.77 (dd, J = 8.8, 6.0 Hz, 1 H), 7.09–6.92 (m, 2 H), 3.65 (s, 3 H), 2.57 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 164.06, 161.58, 157.14 (d, J = 3.4 Hz), 154.99, 134.64 (d, J = 11.0 Hz), 131.27 (d, J = 10.3 Hz), 129.35 (d, J = 11.4 Hz), 111.36 (d, J = 23.3 Hz), 100.63 (d, J = 27.7 Hz), 29.22, 21.36.
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2,4-Dimethyl-3-oxo-3,4-dihydroquinoxaline-6-carbonitrile (2i)[20]
Yellow solid; yield: 44.8 mg (45%).
1H NMR (400 MHz, CDCl3): δ = 8.11 (d, J = 1.2 Hz, 1 H), 7.76 (dd, J = 6.0, 1.4 Hz, 1 H), 7.38 (d, J = 5.6 Hz, 1 H), 3.72 (s, 3 H), 2.61 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 160.78, 154.75, 136.52, 133.78, 132.25, 132.20, 118.04, 114.71, 107.09, 29.32, 21.67.
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3-Methyl-1-(p-tolyl)quinoxalin-2(1H)-one (2j)[21]
Yellow solid; yield: 87.6 mg (70%).
1H NMR (400 MHz, CDCl3): δ = 7.79–7.71 (m, 1 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.26–7.20 (m, 2 H), 7.08 (d, J = 7.6 Hz, 2 H), 6.65–6.57 (m, 1 H), 2.56 (s, 3 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.16, 155.02, 139.41, 134.24, 133.11, 132.49, 130.88, 129.12, 128.97, 127.85, 123.63, 115.49, 21.43, 21.28.
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3-Methyl-1-(2-methylbenzyl)quinoxalin-2(1H)-one (2k)[10]
White solid; yield: 100.4 mg (76%).
1H NMR (400 MHz, CDCl3): δ = 7.71–7.63 (m, 1 H), 7.21–7.14 (m, 1 H), 7.13–7.08 (m, 1 H), 7.07–7.01 (m, 1 H), 6.97 (t, J = 4.8 Hz, 1 H), 6.87–6.77 (m, 2 H), 6.44 (d, J = 5.2 Hz, 1 H), 5.22 (s, 2 H), 2.49 (s, 3 H), 2.30 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.10, 154.82, 134.63, 132.59, 132.36, 132.18, 130.26, 129.32, 129.19, 127.01, 126.11, 124.20, 123.36, 114.25, 43.50, 21.37, 18.94.
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3-Methyl-1-(4-methylbenzyl)quinoxalin-2(1H)-one (2l)[18]
White solid; yield: 99.1 mg (75%).
1H NMR (400 MHz, CDCl3): δ = 7.77 (d, J = 5.6 Hz, 1 H), 7.36–7.28 (m, 1 H), 7.25–7.17 (m, 2 H), 7.10 (dd, J = 21.8, 5.4 Hz, 4 H), 5.38 (s, 2 H), 2.63 (s, 3 H), 2.24 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.11, 154.88, 137.01, 132.60, 132.30, 132.02, 129.24, 129.20, 126.63, 123.21, 114.14, 45.29, 21.38, 20.75.
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1-(4-(tert-Butyl)benzyl)-3-methylquinoxalin-2(1H)-one (2m)[19]
Yellow solid; yield: 124.1 mg (81%).
1H NMR (400 MHz, CDCl3): δ = 7.78 (dd, J = 5.4, 1.0 Hz, 1 H), 7.40–7.34 (m, 1 H), 7.33–7.19 (m, 4 H), 7.18 (d, J = 5.6 Hz, 2 H), 5.43 (s, 2 H), 2.64 (s, 3 H), 1.25 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 158.26, 154.98, 150.37, 132.69, 132.48, 132.02, 129.31, 126.51, 125.59, 123.32, 114.27, 45.33, 34.25, 31.07, 21.47.
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1-(4-Chlorobenzyl)-3-methylquinoxalin-2(1H)-one (2n)[19]
Yellow solid; yield: 113.8 mg (80%).
1H NMR (400 MHz, CDCl3): δ = 7.81 (dd, J = 5.4, 1.0 Hz, 1 H), 7.44–7.35 (m, 1 H), 7.33–7.22 (m, 3 H), 7.20–7.13 (m, 3 H), 5.43 (s, 2 H), 2.64 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.30, 155.00, 133.66, 133.40, 132.76, 132.21, 129.55, 129.51, 128.94, 128.22, 123.67, 114.01, 45.11, 21.53.
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1-(3-Bromobenzyl)-3-methylquinoxalin-2(1H)-one (2o)[19]
White solid; yield: 131.6 mg (80%).
1H NMR (400 MHz, CDCl3): δ = 7.80 (dd, J = 5.4, 1.0 Hz, 1 H), 7.42–7.33 (m, 3 H), 7.32–7.23 (m, 1 H), 7.19–7.09 (m, 3 H), 5.41 (s, 2 H), 2.64 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.15, 154.84, 137.39, 132.63, 132.09, 130.67, 130.23, 129.63, 129.46, 129.43, 125.27, 123.58, 122.77, 113.89, 45.03, 21.43.
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3-Methyl-1-(4-(trifluoromethyl)benzyl)quinoxalin-2(1H)-one (2p)[10]
White solid; yield: 71.6 mg (45%).
1H NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 8.0 Hz, 1 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.41 (t, J = 7.8 Hz, 1 H), 7.39–7.26 (m, 3 H), 7.15 (dd, J = 8.4, 1.2 Hz, 1 H), 5.54 (s, 2 H), 2.66 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.42, 155.11, 139.27, 132.89, 132.27, 130.02 (q, J = 32.3 Hz), 129.75, 129.70, 127.14, 125.89 (q, J = 3.7 Hz), 123.89, 123.85 (q, J = 270.4 Hz), 113.98, 45.44, 21.59.
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3-Methyl-1-propylquinoxalin-2(1H)-one (2q)[10]
White solid; yield: 80.9 mg (80%).
1H NMR (400 MHz, CDCl3): δ = 7.79 (dd, J = 5.2, 1.2 Hz, 1 H), 7.54–7.45 (m, 1 H), 7.35–7.24 (m, 2 H), 4.24–4.15 (m, 2 H), 2.59 (s, 3 H), 1.89–1.73 (m, 2 H), 1.05 (t, J = 5.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.21, 154.73, 132.73, 132.26, 129.48, 129.28, 123.18, 113.46, 43.56, 21.36, 20.44, 11.21.
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1-Butyl-3-methylquinoxalin-2(1H)-one (2r)[10]
White solid; yield: 83.3 mg (77%).
1H NMR (400 MHz, CDCl3): δ = 7.84–7.75 (m, 1 H), 7.55–7.45 (m, 1 H), 7.35–7.25 (m, 2 H), 4.28–4.18 (m, 2 H), 2.59 (s, 3 H), 1.80–1.67 (m, 2 H), 1.56–1.41 (m, 2 H), 1.00 (t, J = 7.4 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.25, 154.77, 132.81, 132.30, 129.54, 129.34, 123.23, 113.49, 41.95, 29.18, 21.41, 20.17, 13.66.
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1-Isobutyl-3-methylquinoxalin-2(1H)-one (2s)[16h]
White solid; yield: 80.0 mg (74%).
1H NMR (400 MHz, CDCl3): δ = 7.69 (d, J = 8.0 Hz, 1 H), 7.43–7.33 (m, 1 H), 7.25–7.14 (m, 2 H), 4.02 (d, J = 7.6 Hz, 2 H), 2.49 (s, 3 H), 2.22–2.09 (m, 1 H), 0.90 (d, J = 6.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 158.25, 155.16, 132.70, 132.58, 129.50, 129.13, 123.16, 113.86, 48.77, 27.05, 21.47, 20.05.
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1-Hexyl-3-methylquinoxalin-2(1H)-one (2t)[22]
Light-yellow solid; yield: 58.7 mg (48%).
1H NMR (400 MHz, CDCl3): δ = 7.80 (dd, J = 8.0, 1.6 Hz, 1 H), 7.55–7.45 (m, 1 H), 7.36–7.24 (m, 2 H), 4.27–4.17 (m, 2 H), 2.59 (s, 3 H), 1.80–1.67 (m, 2 H), 1.53–1.42 (m, 2 H), 1.41–1.29 (m, 4 H), 1.05–0.70 (m, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.26, 154.74, 132.81, 132.31, 129.54, 129.35, 123.22, 113.48, 42.21, 31.34, 27.08, 26.56, 22.42, 21.41, 13.89.
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1-(Cyclopropylmethyl)-3-methylquinoxalin-2(1H)-one (2u)[22]
Light-yellow solid; yield: 83.6 mg (78%).
1H NMR (400 MHz, CDCl3): δ = 7.80 (dd, J = 8.0, 1.6 Hz, 1 H), 7.54–7.45 (m, 1 H), 7.41 (dd, J = 8.8, 1.2 Hz, 1 H), 7.37–7.26 (m, 1 H), 4.18 (d, J = 6.8 Hz, 2 H), 2.59 (s, 3 H), 1.33–1.21 (m, 1 H), 0.60–0.50 (m, 4 H).
13C NMR (100 MHz, CDCl3): δ = 158.37, 154.98, 132.68, 132.48, 129.46, 129.26, 123.18, 113.70, 45.91, 21.46, 9.44, 3.96.
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1-(But-2-yn-1-yl)-3-methylquinoxalin-2(1H)-one (2v)[18]
White solid; yield: 81.7 mg (77%).
1H NMR (400 MHz, CDCl3): δ = 7.79 (d, J = 5.2 Hz, 1 H), 7.54 (t, J = 5.2 Hz, 1 H), 7.45 (d, J = 5.6 Hz, 1 H), 7.34 (t, J = 5.0 Hz, 1 H), 4.97 (s, 2 H), 2.59 (s, 3 H), 1.77 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.13, 154.03, 132.67, 131.75, 129.40, 129.26, 123.57, 114.20, 80.84, 72.00, 31.83, 21.39, 3.40.
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1-Allyl-3-methylquinoxalin-2(1H)-one (2w)[17]
Yellow solid; yield: 71.1 mg (71%).
1H NMR (400 MHz, CDCl3): δ = 7.81 (dd, J = 7.8, 1.4 Hz, 1 H), 7.53–7.43 (m, 1 H), 7.37–7.22 (m, 2 H), 6.01–5.85 (m, 1 H), 5.31–5.22 (m, 1 H), 5.21–5.10 (m, 1 H), 4.90 (dt, J = 5.0, 1.8 Hz, 2 H), 2.61 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 158.32, 154.64, 132.72, 132.35, 130.54, 129.43, 129.39, 123.48, 117.95, 114.08, 44.36, 21.46.
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Conflict of Interest
The authors declare no conflict of interest.
Supporting Information
- Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/s-0043-1775495.
- Supporting Information
-
References
- 1a Li X, Yang K, Li W, Xu W. Drugs Future 2006; 31: 979
- 1b Akins PT, Atkinson RP. Curr. Med. Res. Opin. 2002; 18: 9
- 2a Carta A, Piras S, Loriga G, Paglietti G. Mini-Rev. Med. Chem. 2006; 6: 1179
- 2b Liang Q, Zhang Y, Huang M, Xiao Y, Xiao F. Mol. Med. Rep. 2019; 19: 1256
- 2c Xie W, Wu Y, Zhang J, Mei Q, Zhang Y, Zhu N, Liu R, Zhang H. Eur. J. Med. Chem. 2018; 145: 35
- 3a Xie W, Xie S, Zhou Y, Tang X, Liu J, Yang W, Qiu M. Eur. J. Med. Chem. 2014; 81: 22
- 3b Abbas H.-AS, Al-Marhabi AR, Eissa SI, Ammar YA. Bioorg. Med. Chem. 2015; 23: 6560
- 4 Qin X, Hao X, Han H, Zhu S, Yang Y, Wu B, Hussain S, Parveen S, Jing C, Ma B, Zhu C. J. Med. Chem. 2015; 58: 1254
- 5 Nishio T. J. Chem. Soc., Perkin Trans. 1 1990; 565
- 6 Kalinin AA, Mamedov VA. Russ. J. Org. Chem. 2009; 45: 1098
- 7 Yuan J, Fu J, Yin J, Dong Z, Xiao Y, Mao P, Qu L. Org. Chem. Front. 2018; 5: 2820
- 8a Yang L, Gao P, Duan X.-H, Gu Y.-R, Guo LN. Org. Lett. 2018; 20: 1034
- 8b Zheng K, Chen C, Wang Y, Xu H, Ge K, Shen C. Org. Lett. 2025; 27: 4747
- 8c Dong J, Xuan L, Wang C, Zhao C, Wang H, Yan Q, Wang W, Chen F. Chin. J. Org. Chem. 2024; 44: 111
- 8d Hong Y, Xu J, Chen A, Du Y, Wang G, Shen J, Zhang P. Org. Lett. 2025; 27: 2526
- 9 Peng S, Liu JJ, Yang L. Org. Biomol. Chem. 2021; 19: 9705
- 10 Liu X, Guo Z, Liu Y, Chen X, Li J, Zou D, Wu Y, Wu Y. Org. Biomol. Chem. 2022; 20: 1391
- 11 Liu F, Ye Z.-P, Hu Y.-Z, Gao J, Zheng L, Chen K, Xang H.-Y, Chen X.-Q, Yang H. J. Org. Chem. 2021; 86: 11905
- 12 Zhang L, He J, Zhang P, Zheng K, Shen C. Mol. Catal. 2022; 519: 112145
- 13a Xu J, Zhang Y, Xu R, Wang Y, Shen J, Li W. Org. Chem. Front. 2024; 11: 5122
- 13b Zheng K, Wang Z, Wang Y, Chen C, Shen C. Adv. Synth. Catal. 2025; 367: e202500018
- 13c Li Y, Xu J, Wang Y, Xu R, Zhao Y, Li W. J. Org. Chem. 2025; 90: 1683
- 14 Xie L.-Y, Jiang L.-L, Tan J.-X, Wang Y, Xu X.-Q, Zhang B, Zhong C, He WM. ACS Sustainable Chem. Eng. 2019; 7: 14153
- 15a Mane KD, Kamble RB, Suryavanshi G. New J. Chem. 2019; 43: 7403
- 15b Kang W.-J, Li B, Duan M, Pan G, Sun W, Ding A, Zhang Y, Houk KN, Guo H. Angew. Chem. Int. Ed. 2022; 61: e202211562
- 15c Kang W.-J, Li B, Zhao Z, Sun S, Feng C, Hu K, Houk KN, Guo H. ACS Catal. 2023; 13: 13588
- 15d Li J, Xu J, Chen B, Pang Q, Shen J, Wang K, Zhang P. J. Org. Chem. 2025; 90: 1354
- 16a Xia P.-J, Hu Y.-Z, Ye Z.-P, Li X.-J, Xiang H.-Y, Yang H. J. Org. Chem. 2020; 85: 3538
- 16b Sau S, Takizawa S, Kim HY, Oh K. Org. Lett. 2024; 26: 8821
- 16c Carrer A, Brion JD, Messaoudi S, Alami M. Org. Lett. 2013; 15: 5606
- 16d Pal B, Mal P. Org. Lett. 2025; 27: 978
- 16e Chen D, Bao W. Adv. Synth. Catal. 2010; 352: 955
- 16f Sau S, Mal P. Eur. J. Org. Chem. 2022; e202200425
- 16g Liu S, Huang Y, Qing F.-L, Xu X.-H. Org. Lett. 2018; 20: 5497
- 16h Ghosh P, Kwon NY, Kim S, Han S, Lee SH, An W, Mishra NK, Han SB, Kim IS. Angew. Chem. Int. Ed. 2021; 60: 191
- 16i Su H.-Y, Zhu X.-L, Huang Y, Xu X.-H, Qing F.-L. Chem. Commun. 2020; 56: 12805
- 16j Gao R, Wang F, Geng X, Li C.-Y, Wang L. Org. Lett. 2022; 24: 7118
- 17 Wang L, Zhao J, Sun Y, Zhang H.-Y, Zhang Y. Eur. J. Org. Chem. 2019; 6935
- 18 Zhu Y, Zhang Y, Zhao X, Lu K. Org. Biomol. Chem. 2024; 22: 8951
- 19 Wang J, Wang Y, Lin W, Yang A, Wang Y, Wang J, Zhen H, Ge H. J. Org. Chem. 2024; 89: 17482
- 20 Ramkumar N, Plantus K, Ozola M, Mishnev A, Nikolajeva V, Senkovs M, Ošeka M, Veliks J. New J. Chem. 2023; 47: 20642
- 21 Xue W, Su Y, Wang K.-H, Zhang R, Feng Y, Cao L, Huang D, Hu Y. Org. Biomol. Chem. 2019; 17: 6654
- 22 Zhang T.-B, Guan X.-D, Gao Y, Lu S.-C, Li B.-L. Org. Biomol. Chem. 2024; 22: 3439
Corresponding Authors
Publication History
Received: 18 April 2025
Accepted after revision: 20 May 2025
Article published online:
12 June 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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References
- 1a Li X, Yang K, Li W, Xu W. Drugs Future 2006; 31: 979
- 1b Akins PT, Atkinson RP. Curr. Med. Res. Opin. 2002; 18: 9
- 2a Carta A, Piras S, Loriga G, Paglietti G. Mini-Rev. Med. Chem. 2006; 6: 1179
- 2b Liang Q, Zhang Y, Huang M, Xiao Y, Xiao F. Mol. Med. Rep. 2019; 19: 1256
- 2c Xie W, Wu Y, Zhang J, Mei Q, Zhang Y, Zhu N, Liu R, Zhang H. Eur. J. Med. Chem. 2018; 145: 35
- 3a Xie W, Xie S, Zhou Y, Tang X, Liu J, Yang W, Qiu M. Eur. J. Med. Chem. 2014; 81: 22
- 3b Abbas H.-AS, Al-Marhabi AR, Eissa SI, Ammar YA. Bioorg. Med. Chem. 2015; 23: 6560
- 4 Qin X, Hao X, Han H, Zhu S, Yang Y, Wu B, Hussain S, Parveen S, Jing C, Ma B, Zhu C. J. Med. Chem. 2015; 58: 1254
- 5 Nishio T. J. Chem. Soc., Perkin Trans. 1 1990; 565
- 6 Kalinin AA, Mamedov VA. Russ. J. Org. Chem. 2009; 45: 1098
- 7 Yuan J, Fu J, Yin J, Dong Z, Xiao Y, Mao P, Qu L. Org. Chem. Front. 2018; 5: 2820
- 8a Yang L, Gao P, Duan X.-H, Gu Y.-R, Guo LN. Org. Lett. 2018; 20: 1034
- 8b Zheng K, Chen C, Wang Y, Xu H, Ge K, Shen C. Org. Lett. 2025; 27: 4747
- 8c Dong J, Xuan L, Wang C, Zhao C, Wang H, Yan Q, Wang W, Chen F. Chin. J. Org. Chem. 2024; 44: 111
- 8d Hong Y, Xu J, Chen A, Du Y, Wang G, Shen J, Zhang P. Org. Lett. 2025; 27: 2526
- 9 Peng S, Liu JJ, Yang L. Org. Biomol. Chem. 2021; 19: 9705
- 10 Liu X, Guo Z, Liu Y, Chen X, Li J, Zou D, Wu Y, Wu Y. Org. Biomol. Chem. 2022; 20: 1391
- 11 Liu F, Ye Z.-P, Hu Y.-Z, Gao J, Zheng L, Chen K, Xang H.-Y, Chen X.-Q, Yang H. J. Org. Chem. 2021; 86: 11905
- 12 Zhang L, He J, Zhang P, Zheng K, Shen C. Mol. Catal. 2022; 519: 112145
- 13a Xu J, Zhang Y, Xu R, Wang Y, Shen J, Li W. Org. Chem. Front. 2024; 11: 5122
- 13b Zheng K, Wang Z, Wang Y, Chen C, Shen C. Adv. Synth. Catal. 2025; 367: e202500018
- 13c Li Y, Xu J, Wang Y, Xu R, Zhao Y, Li W. J. Org. Chem. 2025; 90: 1683
- 14 Xie L.-Y, Jiang L.-L, Tan J.-X, Wang Y, Xu X.-Q, Zhang B, Zhong C, He WM. ACS Sustainable Chem. Eng. 2019; 7: 14153
- 15a Mane KD, Kamble RB, Suryavanshi G. New J. Chem. 2019; 43: 7403
- 15b Kang W.-J, Li B, Duan M, Pan G, Sun W, Ding A, Zhang Y, Houk KN, Guo H. Angew. Chem. Int. Ed. 2022; 61: e202211562
- 15c Kang W.-J, Li B, Zhao Z, Sun S, Feng C, Hu K, Houk KN, Guo H. ACS Catal. 2023; 13: 13588
- 15d Li J, Xu J, Chen B, Pang Q, Shen J, Wang K, Zhang P. J. Org. Chem. 2025; 90: 1354
- 16a Xia P.-J, Hu Y.-Z, Ye Z.-P, Li X.-J, Xiang H.-Y, Yang H. J. Org. Chem. 2020; 85: 3538
- 16b Sau S, Takizawa S, Kim HY, Oh K. Org. Lett. 2024; 26: 8821
- 16c Carrer A, Brion JD, Messaoudi S, Alami M. Org. Lett. 2013; 15: 5606
- 16d Pal B, Mal P. Org. Lett. 2025; 27: 978
- 16e Chen D, Bao W. Adv. Synth. Catal. 2010; 352: 955
- 16f Sau S, Mal P. Eur. J. Org. Chem. 2022; e202200425
- 16g Liu S, Huang Y, Qing F.-L, Xu X.-H. Org. Lett. 2018; 20: 5497
- 16h Ghosh P, Kwon NY, Kim S, Han S, Lee SH, An W, Mishra NK, Han SB, Kim IS. Angew. Chem. Int. Ed. 2021; 60: 191
- 16i Su H.-Y, Zhu X.-L, Huang Y, Xu X.-H, Qing F.-L. Chem. Commun. 2020; 56: 12805
- 16j Gao R, Wang F, Geng X, Li C.-Y, Wang L. Org. Lett. 2022; 24: 7118
- 17 Wang L, Zhao J, Sun Y, Zhang H.-Y, Zhang Y. Eur. J. Org. Chem. 2019; 6935
- 18 Zhu Y, Zhang Y, Zhao X, Lu K. Org. Biomol. Chem. 2024; 22: 8951
- 19 Wang J, Wang Y, Lin W, Yang A, Wang Y, Wang J, Zhen H, Ge H. J. Org. Chem. 2024; 89: 17482
- 20 Ramkumar N, Plantus K, Ozola M, Mishnev A, Nikolajeva V, Senkovs M, Ošeka M, Veliks J. New J. Chem. 2023; 47: 20642
- 21 Xue W, Su Y, Wang K.-H, Zhang R, Feng Y, Cao L, Huang D, Hu Y. Org. Biomol. Chem. 2019; 17: 6654
- 22 Zhang T.-B, Guan X.-D, Gao Y, Lu S.-C, Li B.-L. Org. Biomol. Chem. 2024; 22: 3439
