Cross-Dehydrogenative Coupling Reaction and Arylation of Quinoxalin-2(1H)-ones under Iodide/Peroxide Conditions

Yujuan Wu; Xianglong Chu; Di Yang; Chen Ma; Caixia Xie

doi:10.1055/a-1489-8711

SynOpen, Table of Contents

CC BY-NC-ND 4.0 · SynOpen 2021; 05(02): 114-122
DOI: 10.1055/a-1489-8711

letter

Cross-Dehydrogenative Coupling Reaction and Arylation of Quinoxalin-2(1H)-ones under Iodide/Peroxide Conditions

Authors

Yujuan Wu

^aInstitute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
Xianglong Chu

^aInstitute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
Di Yang

^aInstitute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
Chen Ma ∗

^aInstitute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
Caixia Xie

^bSchool of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, P. R. of China

Abstract

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Abstract

A simple method has been developed for the synthesis of 3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one and 3-aryl-quinoxalin-2(1H)-one derivatives through C–H activation of quinoxalin-2(1H)-ones by peroxides and iodide. In this protocol, the peroxide (TBPB) serves as both the radical initiator and aryl source, realizing arylation of quinoxalin-2(1H)-one in a one-step reaction. The methodology has the advantages of being a metal-free strategy and having broad functional group tolerance.

Key words

C–H activation - iodide/peroxide system - metal-free - quinoxalin-2(1H)-one - radical process

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References

References and Notes
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27 Substituted substrates 1 were obtained according to the literature reports.²⁸ Other reagents and solvents were obtained from commercial available reagents and solvents and were used directly without further purification. All the reactions were monitored by thin-layer chromatography. ¹H NMR spectra were recorded on a Bruker Avance 500 spectrometer at 500 MHz using CDCl₃ or DMSO-d₆ as solvent and tetramethylsilane (TMS) as internal standard. ¹³C NMR spectra were run in the same instrument at 125 MHz. HRMS spectra were measured on a Q-TOF instrument in positive-ion mode with an ESI ion source. Melting points were recorded on an XD-4 digital micro melting point apparatus.General Procedure for the TBAI-Catalyzed C–H AcetylationA mixture of quinoxalin-2(1H)-one (1, 0.3 mmol), acetophenone (2, 4.0 equiv.), TBAI (0.2 equiv.), and TBHP (3.0 equiv.) in DCE (2.0 mL) in a sealed tube was heated at 100 °C for 48 h. After completion of the reaction, the tube was then cooled to room temperature and extracted with ethyl acetate (3 × 20 mL). The combined organic phases were dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether/ethyl acetate = 30:1) on silica gel to provide pure product.General Procedure for the I₂-Catalyzed C–H ArylationA mixture of quinoxalin-2(1H)-one (1, 0.3 mmol), I₂ (0.02 equiv), and TBPB (5.0 equiv.) in DCE solvent (2.0 mL) in a sealed tube was heated at 100 °C for 6 h. After completion of the reaction, the tube was then cooled to room temperature and extracted with ethyl acetate (3 × 20 mL). The combined organic phases were dried over anhydrous Na₂SO₄, filtered, and concentrated in vacuo. The residue was purified by column chromatography (petroleum ether/ethyl acetate = 10:1) on silica gel to provide the pure product.(Z)-1-Methyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3a)Yield 86%; yellow solid; mp 176–181 °C. ¹H NMR (500 MHz, CDCl₃): δ = 14.01 (s, 1 H), 8.13 (d, J = 7.3 Hz, 2 H), 8.03 (d, J = 7.1 Hz, 2 H), 7.51–7.47 (m, 4 H), 7.18 (s, 2 H), 7.01 (s, 1 H), 3.65 (s, 1 H). ¹³C NMR (500 MHz, CDCl₃): δ = 190.2, 156.3, 144.6, 138.9, 131.9, 130.2, 128.5, 127.5, 125.3, 124.4, 124.1, 116.8, 114.4, 91.0, 29.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₄N₂O₂: 279.1134; found: 279.1135.Ethyl-(E)-4-[(Z)-2-oxo-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-1(2H)-yl]but-2-enoate (3aa)Yield 46%; yellow solid; mp 167–170 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.82 (s, 1 H), 8.00 (d, J = 7.3 Hz, 2 H), 7.60–7.52 (m, 4 H), 7.28 (d, J = 9.0 Hz, 1 H), 7.24–7.19 (m, 2 H), 7.04 (dt, J ₁ = 15.9 Hz, J ₂ = 4.3 Hz, 1 H), 6.87 (s, 1 H), 5.96 (d, J = 15.9 Hz, 1 H), 5.02 (s, 2 H), 4.11 (q, J = 7.1 Hz, 2 H), 1.18 (t, J = 7.1 Hz, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.7, 165.6, 156.0, 145.2, 142.7, 139.1, 132.4, 129.2, 127.7, 127.4, 125.5, 124.6, 122.1, 117.7, 115.7, 90.1, 60.5, 40.5, 14.5. HRMS (ESI)): m/z [M + H]⁺ calcd for C₂₂H₂₀N₂O₄: 377.1501; found: 377.1502.(Z)-4-[2-Oxo-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-1(2H)-yl]butanoate (3ab)Yield 32%; yellow solid; mp 256–260 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.85 (s, 1 H), 7.99 (d, J = 5.9 Hz, 2 H), 7.59–7.54 (m, 7 H), 7.28–7.22 (m, 2 H), 6.86 (s, 1 H), 4.25–4.22 (m, 2 H), 4.06–4.04 (m, 2 H), 2.51–2.49 (m, 2 H), 1.95 (t, J = 5.8 Hz, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.6, 172.9, 155.8, 145.1, 139.0, 132.4, 129.2, 127.8, 127.4, 125.3, 124.8, 124.5, 117.9, 115.3, 89.9, 60.4, 31.1, 22.3, 14.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₂N₂O₄: 379.1658; found: 379.1653.(Z)-1-[4-(tert-Butyl)benzyl]-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3ac)Yield 76%; yellow solid; mp 188–190 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.86 (s, 1 H), 8.01 (d, J = 7.6 Hz, 2 H), 7.57–7.53 (m, 6 H), 7.33–7.24 (m, 5 H), 6.94 (s, 1 H), 5.43 (s, 2 H), 1.22 (s, 9 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 188.7, 156.0, 150.6, 145.1, 139.0, 133.1, 132.5, 129.3, 127.9, 127.5, 127.0, 125.9, 125.5, 124.7, 117.8, 116.02, 90.29, 45.6, 34.7, 31.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₂₀N₂O₄：411.2073; found: 411.2071.(Z)-1-Cinnamyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3ad)Yield 42%; yellow solid; mp 204–207 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.86 (s, 1 H), 8.00 (d, J = 7.3 Hz, 2 H), 7.59–7.52 (m, 5 H), 7.43–7.40 (m, 3 H), 7.31 (t, J = 7.4 Hz, 2 H), 7.23–7.21 (m, 2 H), 6.90 (s, 1 H), 5.01 (s, 2 H), 2.50 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.7, 155.8, 145.2, 139.1, 136.6, 132.4, 132.1, 129.3, 129.1, 128.2, 127.9, 127.5, 126.8, 125.4, 124.7, 124.6, 123.7, 117.7, 115.9, 44.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₅H₂₀N₂O₂: 381.1603; found: 381.1603.(Z)-1-Butyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3ae)Yield 93%; colorless oily liquid. ¹H NMR (500 MHz, DMSO-d ₆): δ = 14.06 (s, 1 H), 8.04–8.03 (m, 2 H), 7.52–7.45 (m, 3 H), 7.23–7.18 (m, 4 H), 7.02 (s, 1 H), 1.24–1.20 (m, 2 H), 1.80–1.72 (m, 2 H), 1.55–1.45 (m, 2 H), 1.00 (t, J = 7.3 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 190.0, 156.0, 144.7, 139.8, 131.8, 128.5, 127.4, 125.5, 124.2, 124.0, 117.1, 114.5, 90.8, 77.4, 77.0, 76.7, 42.7, 29.1, 20.3, 13.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₂₂N₂O: 321.1603; found: 321.1602.(Z)-1-(Cyclohexylmethyl)-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3af)Yield 65%; colorless oily liquid. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.85 (s, 1 H), 7.95 (d, J = 7.3 Hz, 2 H), 7.55–7.49 (m, 4 H), 7.39 (d, J = 8 Hz, 1 H), 7.22–7.17 (m, 2 H), 6.83 (s, 1 H), 4.05 (s, 2 H), 1.79 (s, 1 H), 1.63 (d, J = 8.15 Hz, 4 H), 1.10–1.08 (m, 6 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.5, 156.0, 145.0, 139.0, 132.3, 129.1, 128.0, 127.4, 125.2, 124.7, 124.4, 117.8, 115.7, 90.0, 48.0, 36.2, 30.6, 26.3, 25.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₂₄N₂O₂: 361.1916; found: 361.1916.(Z)-3-(2-Oxo-2-phenylethylidene)-1-propyl-3,4-dihydroquinoxalin-2(1H)-one (3ag)Yield 63%; colorless oily liquid. ¹H NMR (500 MHz, DMSO-d₆ ): δ = 13.82 (s, 1 H), 7.94 (d, J = 7.1 Hz, 2 H), 7.56–7.54 (m, 2 H), 7.51–7.48 (m, 3 H), 7.41 (d, J = 7.8 Hz, 1 H), 7.23–7.16 (m, 2 H), 6.81 (s, 1 H), 1.68 (q, J = 7.6 Hz, 2 H), 0.96 (t, J = 7.4 Hz, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.5, 155.6, 145.0, 139.0, 132.3, 129.1, 127.7, 127.4, 125.2, 124.7, 124.4, 117.8, 115.4, 89.9, 44.1, 20.5, 11.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₈N₂O₂: 307.1447; found: 307.1448.(Z)-1-Benzyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3ah)Yield 69%; yellow solid; mp 180–184 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.86 (s, 1 H), 8.01 (d, J = 7.1 Hz, 2 H), 7.59–7.54 (m, 4 H), 7.34 (d, J = 4.4 Hz, 4 H), 7.27–7.25 (m, 2 H), 7.20 (t, J = 6.7 Hz, 1 H), 7.14 (t, J = 7.1 Hz, 1 H), 6.84 (s, 1 H), 5.48 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.8, 156.4, 145.1, 139.0, 136.2, 132.5, 129.3, 129.2, 127.8, 127.5, 127.2, 125.4, 124.7, 124.6, 117.8, 116.0, 90.4, 46.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₃H₁₈N₂O₂: 355.1447; found: 355.1446.(Z)-2-[2-Oxo-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-1(2H)-yl]ethyl acetate (3ai)Yield 70%; yellow solid. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.72 (s, 1 H), 8.00 (d, J = 7.1 Hz, 2 H), 7.60–7.57 (m, 2 H), 7.55–7.52 (m, 2 H), 7.37 (d, J = 9.3 Hz, 1 H), 7.25–7.19 (m, 2 H), 6.86 (s, 1 H), 5.07 (s, 2 H), 4.22 (q, J = 7.1 Hz, 2 H), 1.25 (t, J = 7.1 Hz, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ =188.9, 168.0, 156.1, 144.3, 138.9, 132.5, 129.2, 127.8, 127.5, 125.1, 124.8, 124.7, 117.8, 115.3, 90.3, 61.9, 44.7, 14.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₁₈N₂O₄: 351.1345; found: 351.1342. (Z)-3-(2-Oxo-2-phenylethylidene)-1-phenyl-3,4-dihydroquinoxalin-2(1H)-one (3aj) Yield 64%; yellow solid; mp 191–193 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.86 (s, 1 H), 7.99 (d, J = 7.3 Hz, 2 H), 7.67–7.63 (m, 3 H), 7.61–7.57 (m, 3 H), 7.55–7.52 (m, 2 H), 7.46 (d, J = 7.3 Hz, 2 H), 7.20 (t, J = 7.9 Hz, 1 H), 7.05 (t, J = 7.4 Hz, 1 H), 6.88 (s, 1 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 189.0, 155.9, 145.7, 139.0, 136.9, 132.5, 130.6, 130.1, 129.7, 129.3, 129.2, 127.5, 125.1, 124.5, 124.3, 117.5, 116.0, 90.1. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₆N₂O₄: 341.1290; found: 341.1286. (Z)-1,6,7-Trimethyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3ak) Yield 47%; yellow solid; mp 221–224 °C. ¹H NMR (500 MHz, CDCl₃): δ = 14.16 (s, 1 H), 8.03–8.01 (m, 2 H), 7. 50–7.46 (m, 3 H), 7.01 (s, 1 H), 6.97 (s, 1 H), 6.95 (s, 1 H), 3.64 (s, 3 H), 2.31 (s, 3 H), 2.28 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 189.2, 156.2, 145.0, 139.0, 133.1, 131.5, 130.1, 128.5, 127.3, 126.5, 123.2, 117.8, 115.3, 90.4, 29.6, 19.9, 19.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₈N₂O₂: 307.1447; found: 306.1445. (Z)-6,7-Difluoro-1-methyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3al) Yield 74%; yellow solid; mp 286–288 °C. ¹H NMR (500 MHz, CDCl₃): δ = 14.07 (s, 1 H), 8.00 (d, J = 7.2 Hz, 2 H), 7.54–7.45 (m, 4 H), 7.10–7.07 (m, 1 H), 7.00 (s, 1 H), 3.61 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 188.9, 155.8, 145.0, 138.2, 132.1, 130.1, 128.6, 127.4, 106.1, 105.9, 103.8, 91.7, 30.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₂F₂N₂O₂: 315.0945; found: 315.0940. (Z)-1-Methyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydrobenzo[g]quinoxalin-2(1H)-one (3am) Yield 73%; yellow solid; mp 186–190 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.74 (s, 1 H), 8.01–7.98, (m, 3 H), 7.94–7.92 (m, 1 H), 7.85 (s, 1 H), 7.62–7.54 (m, 4 H), 7.45–7.44 (m, 2 H), 6.92 (s, 1 H), 3.67 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 189.6, 156.1, 144.4, 139.0. 132.6, 130.4, 130.2, 129.3, 128.7, 127.9, 127.6, 127.0, 126.1, 125.8, 124.9, 113.1, 112.2, 91.1, 30.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₆N₂O₂: 329.1290; found: 329.1285. (Z)-6,7-Dibromo-1-methyl-3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-one (3an) Yield 51%; yellow solid. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.35 (s, 1 H), 8.01 (s, 1 H), 7.92 (d, J = 5 Hz, 2 H), 7.61–7.49 (m, 4 H), 6.81 (s, 1 H), 3.50 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.9, 155.6, 144.0, 138.7, 132.6, 129.2, 127.5, 125.9, 121.4, 119.6, 118.3, 118.1, 91.3, 30.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₂Br₂N₂O₂: 434.9344; found: 434.9349. (Z)-3-[2-(2-Hydroxyphenyl)-2-oxoethylidene]-1-methyl-3,4-dihydroquinoxalin-2(1H)-one (3ba) Yield 57%; yellow solid; mp 207–209 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.27 (s, 1 H), 12.85 (s, 1 H), 7.90 (d, J = 7.7 Hz, 1 H), 7.68 (d, J = 7.4 Hz, 1 H), 7.48–7.44 (m, 2 H), 6.97–6.93 (m, 2 H), 3.61 (s, 3 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 188.9, 167.4, 156.2, 146.1, 139.1, 132.4, 129.2, 127.5, 127.2, 124.6, 124.5, 124.2, 117.1, 115.8, 89.6, 40.0. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₄N₂O₃: 295.1083; found: 295.1079. (Z)-1-Methyl-3-[2-oxo-2-(o-tolyl)ethylidene]-3,4-dihydroquinoxalin-2(1H)-one (3bb) Yield 33%; yellow solid; mp 144–147 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.54 (s, 1 H), 7.58–7.54 (m, 2 H), 7.42–7.37 (m, 2 H), 7.32–7.22 (m, 4 H), 6.44 (s, 1 H), 3.58 (s, 3 H), 2.46 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 193.8, 155.7, 144.3, 140.7, 136.2, 131.7, 130.5, 128.7, 128.1, 126.4, 125.0, 124.6, 124.4, 117.4, 115.5, 93.9, 30.2, 20.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆N₂O₂: 293.1290; found: 293.1295. (Z)-3-[2-(4-Methoxyphenyl)-2-oxoethylidene]-1-methyl-3,4-dihydroquinoxalin-2(1H)-one (3bc) Yield 74%; yellow solid; mp 199–203 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.76 (s, 1 H), 7.98 (d, J = 10.8 Hz, 2 H), 7.53–7.51 (m, 1 H), 7.42–7.40 (m, 1 H), 7.24–7.21 (m, 2 H), 7.08 (d, J = 8.8 Hz, 2 H), 6.83 (s, 1 H), 3.85 (s, 3 H), 3.60 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.1, 162.9, 156.0, 144.6, 131.8, 129.6, 128.6, 125.2, 124.5, 124.4, 117.1, 115.5, 114.5, 89.8, 55.9, 30.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆N₂O₃: 309.1239; found: 309.1238. (Z)-1-Methyl-3-[2-oxo-2-(p-tolyl)ethylidene]-3,4-dihydroquinoxalin-2(1H)-one (3bd) Yield 62%; yellow solid; mp 179–181 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.79 (s, 1 H), 7.88 (d, J = 8.0 Hz, 2 H), 7.53 (d, J = 9.0 Hz, 2 H), 7.41 (d, J = 7.2 Hz, 2 H), 7.33 (d, J = 7.9 Hz, 2 H), 7.25–7.20 (m, 2 H), 6.82 (s, 1 H), 3.58 (s, 3 H), 2.37 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 188.5, 155.8, 144.9, 142.6, 136.4, 129.8, 128.7, 127.5, 125.1, 124.5, 117.3, 115.5, 89.9, 30.2, 21.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆N₂O₂: 293.1290; found: 293.1288. (Z)-3-[2-(4-Bromophenyl)-2-oxoethylidene]-1-methyl-3,4-dihydroquinoxalin-2(1H)-one (3be) Yield 61%; yellow solid; mp 263–265 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.84 (s, 1 H), 7.94 (d, J = 8.6 Hz, 2 H), 7.75 (d, J = 8.6 Hz, 2 H), 7.60–7.58 (m, 1 H), 7.45–7.43 (m, 1 H), 7.30–7.22 (m, 2 H), 6.84 (s, 1 H), 3.61 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 187.4, 155.7, 145.5, 138.1, 132.3, 129.5, 128.9, 126.3, 124.9, 124.6, 117.6, 115.6, 100.0, 89.7, 30.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₃BrN₂O₂: 357.0239; found: 357.0241. (Z)-3-[2-(4-Chlorophenyl)-2-oxoethylidene]-1-methyl-3,4-dihydroquinoxalin-2(1H)-one (3bf) Yield 51%; yellow solid; mp 248–253 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.83 (s, 1 H), 8.01 (d, J = 8.6 Hz, 2 H), 7.60 (d, J = 8.6 Hz, 2 H), 7.44 (d, J = 7.7 Hz, 2 H), 7.28–7.24 (m, 2 H), 6.84 (s, 1 H), 3.60 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 187.2, 155.7, 145.4, 137.7, 137.2, 129.4, 128.9, 125.0, 124.6, 117.6, 115.6, 89.7, 30.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₃ClN₂O₂: 313.0744; found: 313.0742. (Z)-3-[2-(4-Iodophenyl)-2-oxoethylidene]-1-methyl-3,4-dihydroquinoxalin-2(1H)-one (3bg) Yield 49%; yellow solid; mp 204–206 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.83 (s, 1 H), 7.92 (d, J = 8 Hz, 2 H), 7.76 (d, J = 8.5 Hz, 2 H), 7.58–7.56 (m, 1 H), 7.44–7.42 (m, 1 H), 7.29–7.21 (m, 2 H), 6.82 (s, 1 H), 3.60 (s, 3 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 187.6, 155.7, 145.4, 138.4, 138.2, 129.3, 128.9, 125.0, 124.9, 124.6, 117.6, 115.6, 100.4, 89.6, 30.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₃IN₂O₂: 405.0100; found: 405.0102. (Z)-3-[2-(2-Fluorophenyl)-2-oxoethylidene]-1-methyl-3,4-dihydroquinoxalin-2(1H)-one (3bh) Yield 70%; yellow solid; mp 145–150 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.75 (s, 1 H), 7.88–7.84 (m, 1 H), 7.60 (d, J = 6.5 Hz, 2 H), 7.44 (d, J = 7.9 Hz, 2 H), 7.37–7.32 (m, 2 H), 7.29–7.22 (m, 2 H), 6.75 (s, 1 H), 3.59 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 185.4, 161.5, 157.5, 155.6, 145.2, 134.0, 133.9 (J = 35.5 Hz), 130.5, 129.0, 127.7, 127.6 (J = 49.0 Hz), 125.3 (J = 13.0 Hz), 125.0, 124.9, 124.5, 117.7, 117.2 (J = 250.6 Hz), 117.0, 115.6, 94.2, 30.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₃FN₂O₂: 297.1039; found: 297.1041. (Z)-1-Methyl-3-{2-oxo-2-[2-(trifluoromethyl)phenyl]ethylidene}-3,4-dihydroquinoxalin-2(1H)-one (3bi) Yield 35%; yellow solid; mp 191–195 °C. ¹H NMR (500 MHz, DMSO-d ₆): δ = 13.29 (s, 1 H), 7.84–7.76 (m, 2 H), 7.65–7.70 (m, 3 H), 7.43 (d, J = 7.7 Hz, 1 H), 7.28–7.21, (m, 2 H), 6.32 (s, 1 H), 3.58 (s, 3 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 191.7, 155.4, 144.6, 140.9, 133.1, 130.6, 128.9, 128.8 (J = 65.4 Hz), 127.1, 127.0 (J = 21.2 Hz), 126.2, 126.0 (J = 124.8 Hz), 125.5, 125.0, 124.7, 124.5 (J = 61.7 Hz), 123.3, 117.6, 115.6, 93.5, 30.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₃F₃N₂O₂: 347.1007; found: 347.1002. (Z)-1-Methyl-3-[2-(naphthalen-2-yl)-2-oxoethylidene]-3,4-dihydroquinoxalin-2(1H)-one (3bj) Yield 78%; yellow solid; mp 164–167 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 13.69 (s, 1 H), 8.52 (d, J = 7.6 Hz, 1 H), 8.09 (d, J = 6.6 Hz, 1 H), 8.02–8.01 (m, 1 H), 7.84 (d, J = 5.6 Hz, 1 H), 7.62–7.59 (m, 4 H), 7.43 (d, J = 6.0 Hz, 1 H), 7.29–7.23 (m, 2 H), 6.61 (s, 1 H), 3.59 (s, 3 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 193.2, 155.8, 144.6, 138.6, 133.9, 131.4, 130.0, 128.9, 128.8, 127.5, 126.8, 126.7, 126.0, 125.7, 125.0, 124.7, 124.5, 117.4, 115.6, 94.5, 30.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₆N₂O₂: 329.1290; found: 329.1286. 1-Methyl-3-phenylquinoxalin-2(1H)-one (4a) Yield 88%; white solid; mp 114–116 °C. ¹H NMR (500 MHz, CDCl₃): δ = 8.31–8.30 (m, 2 H), 7.95 (d, J = 9.2 Hz, 1 H), 7.59 (t, J = 7.1 Hz, 1 H), 7.49–7.48 (m, 3 H), 7.39–7.34 (m, 2 H), 3.78 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 154.8, 154.2, 136.1, 133.4, 133.1, 130.5, 130.3, 129.6, 128.1, 123.8, 113.6, 29.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₂N₂O: 237.1028; found: 237.1028. Ethyl 2-[2-Oxo-3-phenylquinoxalin-1(2H)-yl]acetate (4aa) Yield 47%; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.33–8.31 (m, 2 H), 7.99 (dd, J ₁ = 8.0 Hz, J ₂ = 1.4 Hz, 1 H), 7.57–7.52 (m, 1 H), 7.51–7.47 (m, 3 H), 7.41–7.36 (m, 1 H), 7.13 (d, J = 8.4 Hz, 1 H), 5.10 (s, 2 H), 4.30 (q, J = 7.2 Hz, 2 H), 1.31 (t, J = 7.1 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 167.2, 154.3, 154.0, 135.7, 133.2, 132.5, 130.8, 130.5, 129.6, 128.1, 124.1, 113.1, 62.1, 43.8, 14.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₆N₂O₃: 309.1239; found: 309.1238. 1-[4-(tert-Butyl)benzyl]-3-phenylquinoxalin-2(1H)-one (4ab) Yield 37%; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.29–8.27 (m, 2 H), 7.89 (d, J = 6.4 Hz, 1 H), 7.43–7.41 (m, 4 H), 7.28–7.25 (m, 5 H), 7.18 (s, 2 H), 5.47 (s, 2 H), 1.20 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.8, 154.3, 150.7, 136.1, 133.4, 132.9, 132.3, 130.6, 130.4, 130.3, 129.7, 128.1, 126.8, 125.9, 123.8, 114.5, 45.9, 34.5, 31.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₅H₂₄N₂O: 369.1967; found: 369.1669. 1-Benzyl-3-phenylquinoxalin-2(1H)-one (4ac) Yield 51%; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.38–8.35 (m, 2 H), 7.97 (d, J = 9.4 Hz, 1 H), 7.51–7.49 (m, 3 H), 7.46–7.43 (m, 1 H), 7.36–7.26 (m, 7 H), 5.58 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.8, 154.3, 136.0, 135.4, 133.4, 132.8, 130.6, 130.5, 130.4, 129.7, 129.0, 128.1, 127.7, 127.0, 123.8, 114.4, 46.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₁₆N₂O: 313.1341; found: 313.1343. 1-(2-Oxo-2-phenylethyl)-3-phenylquinoxalin-2(1H)-one (4ad) Yield 32%; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.34–8.31 (m, 2 H), 8.12–8.10 (m, 2 H), 8.01 (dd, J ₁ = 8.0 Hz, J ₂ = 1.4 Hz, 1 H), 7.71–7.67 (m, 2 H), 7.59–7.55 (m, 2 H), 7.49–7.48 (m, 4 H), 7.39–7.35 (m, 1 H), 7.01 (d, J = 9.1 Hz, 1 H), 5.82 (s, 2 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 192.9, 154.3, 153.2, 136.0, 135.0, 133.4, 132.8, 131.2, 130.9, 130.3, 129.8, 129.5, 129.0, 128.8, 128.5, 124.3, 115.9, 50.9. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₂H₁₆N₂O₂: 341.1290; found: 341.1290. 3-Phenyl-1-propylquinoxalin-2(1H)-one (4ae) Yield 28%; colorless oily liquid. ¹H NMR (400 MHz, CDCl₃): δ = 8.32–8.30 (m, 2 H), 7.97–7.95 (m, 1 H), 7.58–7.54 (m, 1 H), 7.49–7.47 (m, 3 H), 7.38–7.33 (m, 2 H), 4.31–4.27 (m, 2 H), 1.90–1.81 (m, 2 H), 1.11 (t, J = 7.4 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.4, 154.2, 136.1, 133.4, 132.6, 130.7, 130.3, 130.2, 129.6, 128.1, 123.5, 113.6, 44.1, 20.7, 11.5. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₇N₂O: 265.1341; found: 265.1345. 1,3-Diphenylquinoxalin-2(1H)-one (4af) Yield 94%; white solid. ¹H NMR (400 MHz, CDCl₃): δ = 8.40–8.38 (m, 2 H), 8.00–7.98 (m, 2 H), 7.66–7.56 (m, 4 H), 7.49–7.47 (m, 3 H), 7.37–7.34 (m, 4 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.5, 136.1, 135.7, 134.2, 133.0, 130.5, 130.3, 130.1, 130.0, 129.7, 129.4, 128.3, 128.1, 123.9, 115.4. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₁₄N₂O: 299.1184; found: 299.1180. 1,6,7-Trimethyl-3-phenylquinoxalin-2(1H)-one (4ag) Yield 66%; white solid; mp 154–156 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.29–8.26 (m, 2 H), 7.71 (s, 1 H), 8.49–8.35 (m, 4 H), 7.11 (s, 1 H), 3.76 (s, 3 H), 2.45 (s, 3 H), 2.38 (s, 3 H). ¹³C NMR (101 MHz, DMSO-d ₆): δ = 167.8, 154.5, 152.1, 140.9, 137.0, 133.4, 132.8, 131.2, 129.7, 129.1, 128.3, 115.5, 29.7, 20.5, 19.2. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₇H₁₆N₂O: 265.1341; found: 265.1338. 6,7-Chloro-1-methyl-3-phenylquinoxalin-2(1H)-one (4ah) Yield 95%; white solid; mp 172–174 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.31–8.29 (m, 2 H), 8.02 (s, 1 H), 7.51–7.47 (m, 3 H), 7.42 (s, 1 H), 3.72 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 155.2, 154.1, 135.4, 134.3, 132.7, 132.2, 131.1, 130.9, 130.0, 128.2, 115.1, 29.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₁₀Cl₂N₂O: 306.1660; found: 306.1661. 1-Methyl-3-phenylbenzo[g]quinoxalin-2(1H)-one (4ai) Yield 70%; yellow solid; mp 162–164 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.45 (s, 1 H), 8.34–8.32 (m, 2 H), 8.00–7.91 (m, 2 H), 7.62 (s, 1 H), 7.59–7.55 (m, 1 H), 7.51–7.49 (m, 4 H), 3.83 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 154.8, 154.7, 136.1, 133.8, 132.5, 132.0, 130.5, 129.9, 129.7, 129.7, 128.5, 128.1, 127.9, 127.2, 125.3, 109.8, 29.3. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₉H₁₄N₂O: 287.3420; found: 287.3421.
28 Carrër A, Brion J.-D, Messaoudi S, Alami M. Org. Lett. 2013; 15: 5606

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