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

Yujuan Wu
a  Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
,
Xianglong Chu
a  Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
,
Di Yang
a  Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
,
Chen Ma
a  Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China
,
Caixia Xie
b  School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, P. R. of China
› Author Affiliations
Financial support from the National Science Foundation of China (21572117) and the Shandong Key Research Program (Nos. 2019JZZY021015 and 2019GHY112053) is gratefully acknowledged.


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.

Supporting Information



Publication History

Received: 15 March 2021

Accepted after revision: 21 April 2021

Publication Date:
23 April 2021 (online)

© 2021. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References and Notes

  • 1 El-Hawash SA. M, Habi NS, Kassem MA. Arch. Pharm. Chem. Life Sci. 2006; 339: 564
  • 2 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
  • 3 Ahmed HE. A, Ihmaid SK, Omar AM, Shehata AM, Rateb HS, Zayed MF, Ahmed S, Elaasser MM. Bioorg. Chem. 2018; 76: 332
  • 4 Koltun DO, Parkhill EQ, Vasilevich NI, Glushkov AI, Zilbershtein AI, Ivanov AV, Cole AG, Henderson I, Zautke NA, Brunn SA, Mollova N, Leung K, Chisholm JW, Zablocki J. Bioorg. Med. Chem. Lett. 2009; 19: 2048
  • 5 Shawali AS, Zayed MM, Farghaly TA. J. Heterocycl. Chem. 2005; 42: 185
  • 6 Wu B, Yang Y, Qin X, Zhang S, Jing C, Zhu C, Ma B. Chem. Med. Chem. 2013; 8: 1913
    • 7a Křupková S, Funk P, Soural M, Hlaváč J. ACS Comb.Sci. 2013; 15: 20
    • 7b Paul S, Khanal HD, Clinton CD, Kim SH, Lee YR. Org. Chem. Front. 2019; 6: 231
    • 7c Ramesh B, Reddy CR, Kumar GR, Reddy BV. S. Tetrahedron Lett. 2018; 59: 628
    • 7d Yin K, Zhang R. Org. Lett. 2017; 19: 1530
    • 7e Paul S, Ha JH, Park GE, Lee YR. Adv. Synth. Catal. 2017; 359: 1515
  • 8 Fu J, Yuan J, Zhang Y, Xiao Y, Mao P, Diao X, Qu L. Org. Chem. Front. 2018; 5: 3382
  • 9 Zhou J, Zhou P, Zhao T, Ren Q, Li J. Adv. Synth. Catal. 2019; 361: 5371
  • 10 Chu X, Wu Y, Lu H, Yang B, Ma C. Eur. J. Org. Chem. 2020; 1141
  • 11 Li K.-J, Jiang Y.-Y, Xu K, Zeng C.-C, Sun B.-G. Green Chem. 2019; 21: 4412
  • 12 Wang J, Sun B, Zhang L, Xu T, Xie Y, Jin C. Org. Chem. Front. 2020; 7: 113
    • 13a Gupta A, Deshmukh MS, Jain N. J. Org. Chem. 2017; 82: 4784
    • 13b Wei W, Wang L, Bao P, Shao Y, Yue H, Yang D, Yang X, Zhao X, Wang H. Org. Lett. 2018; 20: 7125
    • 13c Yang Q, Yang Z, Tan Y, Zhao J, Sun Q, Zhang H.-Y, Zhang Y. Adv. Synth. Catal. 2019; 361: 1662
  • 14 Wang L, Zhang Y, Li F, Li X, Hao H.-Y, Zhang J. Adv. Synth. Catal. 2018; 360: 3969
  • 15 Petronijević J, Bugarčić Z, Bogdanović GA, Stefanović S, Janković N. Green Chem. 2017; 19: 707
  • 16 Beletskaya IP, Cheprakov AV. Chem. Rev. 2000; 100: 3009
  • 17 Gandeepan P, Koeller J, Korvorapun K, Mohr J, Ackermann L. Angew. Chem. Int. Ed. 2019; 58: 982
  • 18 Yi H, Zhang G, Wang H, Huang Z, Wang J, Singh AK, Lei A. Chem. Rev. 2017; 117: 9016
  • 19 Chen L, Shi E, Liu Z, Chen S, Wei W, Li H, Xu K, Wan X. Chem. Eur. J. 2011; 17: 4085
  • 20 Bozdyreva KS, Smirnova IV, Maslivets AN. Russ. J. Org. Chem. 2005; 41: 1081
  • 21 Dounay AB, Overman LE. Chem. Rev. 2003; 103: 2945
    • 22a Shen Z, Huang H, Zhu C, Warratz S, Ackermann L. Org. Lett. 2019; 21: 571
    • 22b Shen H, Deng Q, Liu R, Feng Y, Zheng C, Xiong Y. Org. Chem. Front. 2017; 4: 1806
  • 23 Yadav DK. T, Bhanage BM. Synlett 2015; 26: 1862
  • 24 Zhang F, Li LS. Zhang J. Y, Gong H. Sci. Rep. 2019; 9: 2787
  • 25 Yi H, Zhang GT, Wang HM, Huang ZY, Wang J, Singh AK, Lei A. Chem. Rev. 2017; 117: 9016
  • 26 Chen L, Shi ErB, Liu ZJ, Chen SL, Wei W, Li H, Xu K, Wan XB. Chem. Eur. J. 2011; 17: 4085
  • 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