H₂O₂-Promoted Alkylation of Quinoxalin-2(1H)-ones with Styrenes and Dimethyl Sulfoxide

Abstract

A hydrogen peroxide (H₂O₂)-mediated quinoxaline-2(1H)-ones hydrocarbylation reaction has been reported. The reaction is achieved through the difunctionalization of styrene. In this transformation, methyl radical resulting from dimethyl sulfoxide firstly attacks styrenes to provide alkyl radicals which then undergo alkylation at the C3 position of quinoxalin-2(1H)-one. A green, convenient, and simple protocol for the synthesis of 3-alkylquinoxalin-2(1H)-ones was provided.

Key words

hydrocarbylation - quinoxaline-2(1H)-ones - difunctionalization

Publication History

Received: 23 April 2021

Accepted after revision: 12 May 2021

Accepted Manuscript online:
12 May 2021

Article published online:
14 June 2021

• References and Note

• 1a Wu X.-X, Zhu C. Acc. Chem. Res. 2020; 53: 1620
• 1b Yu J.-J, Wu Z, Zhu C. Angew. Chem. Int. Ed. 2018; 57: 17156
• 2a Egami H, Sodeoka M. Angew. Chem. Int. Ed. 2014; 53: 8294
• 2b Chemler SR, Bovino MT. ACS Catal. 2013; 3: 1076
• 2c Muniz K, Martínez C. J. Org. Chem. 2013; 78: 2168
• 2d Huang SX, Ding KL. Angew. Chem. Int. Ed. 2011; 50: 7734
• 2e Bataille CJ. R, Donohoe TJ. Chem. Soc. Rev. 2011; 40: 114
• 2f Minatti A, Muniz K. Chem. Soc. Rev. 2007; 36: 1142
• 2g Chen DJ, Timmons C, Wei H.-X, Li G.-G. J. Org. Chem. 2003; 68: 5742
• 2h Wei H.-X, Siruta S, Li G.-G. Tetrahedron Lett. 2002; 43: 3809
• 2i Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
• 3a Pintauer T, Matyjaszewski K. Chem. Soc. Rev. 2008; 37: 1087
• 3b Eckenhoff WT, Pintauer T. Catal. Rev. Sci. Eng. 2010; 52: 1
• 3c Cao M.-Y, Ren X, Lu Z. Tetrahedron Lett. 2015; 56: 3732
• 3d Clark AJ. Eur. J. Org. Chem. 2016; 2231
• 3e Kindt S, Heinrich MR. Synthesis 2016; 48: 1597
• 4a Monge A, Martinez-Crespo FJ, Cerai AL, Palop JA, Narro S, Senador V, Marin A, Sainz Y, Gonzalez M, Hamilton E, Barker AJ. J. Med. Chem. 1995; 38: 4488
• 4b Ali MM, Ismail MM. F, El-Gaby MS. A, Zahran MA, Ammar YA. Molecules 2000; 5: 864
• 4c Carta A, Piras S, Loriga G, Paglietti G. Mini-Rev. Med. Chem. 2006; 6: 1179
• 4d Liu R, Huang Z.-H, Murray MG, Guo X.-Y, Liu G. J. Med. Chem. 2011; 54: 5747
• 4e Maichrowski J, Gjikaj M, Hübner EG, Bergmann B, Müller IB, Kaufmann DE. Eur. J. Org. Chem. 2013; 2091
• 4f Hussain S, Parveen S, Hao X, Zhang SZ, Wang W, Qin X.-Y, Yang Y.-C, Chen X, Zhu S.-J, Zhu C.-J, Ma B. Eur. J. Med. Chem. 2014; 80: 383
• 4g 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
• 4h ElHawash SA. M, Habib NS, Kassem MA. Arch. Pharm. 2006; 339: 564
• 4i Qin X.-Y, Hao X, Han H, Zhu S.-J, Yang Y.-C, Wu B.-B, Hussain S, Parveen S, Jing C.-J, Ma B, Zhu C.-J. J. Med. Chem. 2015; 58: 1254
• 4j Shahin MI, Abou El Ella DA, Ismail NS. M, Abouzid KA. M. Bioorg. Chem. 2014; 56: 16
• 4k Galal SA, Khairat SH. M, Ragab FA. F, Abdelsamie AS, Ali MM, Soliman SM, Mortier J, Wolber G, El Diwani HI. Eur. J. Med. Chem. 2014; 86: 122
• 4l Willardsen JA, Dudley DA, Cody WL, Chi L, McClanahan TB, Mertz TE, Potoczak RE, Narasimhan LS, Holland DR, Rapundalo ST, Edmunds JJ. J. Med. Chem. 2004; 47: 4089
• 5a Nikam SS, Sahasrabudhe AD, Shastri RK, Ramanathan S. Synthesis 1983; 145
• 5b Udilova N, Kozlov AV, Bieberschulte W, Frei K, Ehrenberger K, Nohl H. Biochem. Pharmacol. 2003; 65: 59
• 5c Nohl H, Bieberschulte W, Dietrich B, Udilova N, Kozlov AV. BioFactors 2003; 19: 79
• 5d Piras S, Loriga M, Carta A, Paglietti G, Paola Costi M, Ferrari S. J. Heterocycl. Chem. 2006; 43: 541
• 5e Mamedov VA, Kalinin AA, Gubaidullin AT, Litvinov IA, Levin YA. Chem. Heterocycl. Compd. 2002; 38: 1504
• 6a Carrër A, Brion JD, Messaoudi S, Alami M. Org. Lett. 2013; 15: 5606
• 6b Carrër A, Brion JD, Alami M, Messaoudi S. Adv. Synth. Catal. 2014; 356: 3821
• 6c Zhang X, Xu B, Xu M.-H. Org. Chem. Front. 2016; 3: 944
• 6d Yuan JW, Liu S.-N, Qu LB. Adv. Synth. Catal. 2017; 359: 4197
• 6e Yin K, Zhang R. Org. Lett. 2017; 19: 1530
• 6f Paul S, Ha JH, Park GE, Lee YR. Adv. Synth. Catal. 2017; 359: 1515
• 6g Kwon SJ, Jung HI, Kim DY. ChemistrySelect 2018; 3: 5824
• 6h Paul S, Khanal HD, Clinton CD, Kim SH, Lee YR. Org. Chem. Front. 2018; 6: 231
• 6i Yin K, Zhang R. Synlett 2018; 29: 597
• 6j Ramesh B, Reddy CR, Kumar GR, Reddy BV. S. Tetrahedron Lett. 2018; 59: 628
• 6k Zeng X, Liu C, Wang X, Zhang J, Wang X, Hu Y. Org. Biomol. Chem. 2017; 15: 8929
• 6l Yuan J.-W, Fu J.-H, Liu S.-N, Xiao Y.-M, Maoa P, Qu L.-B. Org. Biomol. Chem. 2018; 16: 3203
• 6m Gupta A, Deshmukh MS, Jain N. J. Org. Chem. 2017; 82: 4784
• 6n Wei W, Wang L, Bao P, Shao Y, Yue H, Yang D, Yang X, Zhao X, Wang H. Org. Lett. 2018; 20: 7125
• 6o Li Y, Gao M, Wang L, Cui X. Org. Biomol. Chem. 2016; 14: 8428
• 6p Li K.-J, Xu K, Liu Y.-G, Zeng C.-C, Sun B.-G. Adv. Synth. Catal. 2019; 361: 1033
• 6q Yang Q, Yang Z, Tan Y, Zhao J, Sun Q, Zhang H.-Y, Zhang Y. Adv. Synth. Catal. 2019; 361: 1662
• 6r Gao M, Li Y, Xie L, Chauvin R, Cui X. Chem. Commun. 2016; 52: 2846
• 6s Kim Y, Kim DY. Tetrahedron Lett. 2018; 59: 2443
• 6t Liu S, Huang Y, Qing FL, Xu X.-H. Org. Lett. 2018; 20: 5497
• 6u Fu J, Yuan J, Zhang Y, Xiao Y, Mao P, Diao X, Qu L. Org. Chem. Front. 2018; 5: 3382
• 6v Gu Y.-R, Duan X.-H, Chen L, Ma Z.-Y, Gao P, Guo L.-N. Org. Lett. 2019; 21: 917
• 6w Xue W, Su Y, Wang K.-H, Zhang R, Feng Y, Cao L, Huanga D, Hu Y. Org. Biomol. Chem. 2019; 17: 6654
• 6x Xie L.-Y, Jiang L.-L, Tan J.-X, Wang Y, Xu X.-Q, Zhang B, Cao Z, He WM. ACS Sustainable Chem. Eng. 2019; 7: 14153
• 7 Dutta HS, Ahmad A, Khan AA, Kumar M, Raziullah Raziullah, Koley D. Adv. Synth. Catal. 2019; 361: 5534
• 8 Meng N, Wang L.-L, Liu Q.-S, Li Q.-Y, Lv Y.-F, Yue H.-L, Wang X.-J, Wei W. J. Org. Chem. 2020; 85: 6888
• 9 Jin S.-Z, Yao H, Lin S, You X.-Q, Yang Y, Yan Z.-H. Org. Biomol. Chem. 2020; 18: 205
• 10a Eberhardt MK, Colina R. J. Org. Chem. 1988; 53: 1071
• 10b Baptista L, Silva EC. D, Arbilla G. Phys. Chem. Chem. Phys. 2008; 10: 6867
• 10c Sanchez-Cruz P, Santos A, Diaz S, Alegría AE. Chem. Res. Toxicol. 2014; 27: 1380
• 10d Yin K, Zhang RH. Org. Lett. 2017; 19: 1530
• 11 Hydrocarbylation Products 3 – General Procedure Quinoxalin-2(1H)-ones 1 (0.3 mmol), styrene 2 (2 equiv), H₂O₂ (30% in water, 3 equiv), and DMSO (2 mL) were mixed and stirred at 120 ℃ in a sealed tube under N₂ for 12 h. After completion of the reaction, the reaction mixture was cooled to room temperature, water (10 mL) was added, followed by extraction diluted with ethyl acetate (3 × 10 mL). The combined organic portion was dried with anhydrous Na₂SO₄ and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a mixture of petroleum ether and ethyl acetate as eluent to afford various target compounds. Compound 3a was obtained in 81% yield (67.8 mg) according to the general procedure as a white solid. ¹H NMR (400 MHz, CDCl₃): δ = 7.92 (dd, J = 8.0, 1.5 Hz, 1 H), 7.53–7.48 (m, 1 H), 7.47–7.43 (m, 2 H), 7.37–7.31 (m, 1 H), 7.29–7.23 (m, 3 H), 7.19–7.14 (m, 1 H), 4.58 (t, J = 7.7 Hz, 1 H), 3.62 (s, 3 H), 2.32 (m, 1 H), 2.09 (m, 1 H), 0.92 (t, J = 7.4 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 161.39, 154.65, 141.63, 133.00, 132.83, 130.13, 129.64, 128.70, 128.25, 126.51, 123.39, 113.44, 49.15, 29.10, 27.10, 12.42. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₈H₁₈N₂O: 279.1492; found: 279.1488.
• 12 Hydrocarbylation Products 4 – General Procedure Quinoxalin-2(1H)-ones 1 (0.3 mmol), styrene 2 (2 equiv), H₂O₂ (30% in water, 3 equiv), and DMSO (2 mL) were mixed and stirred at 120 °C in a sealed tube under N₂ for 12 h. After completion of the reaction, the reaction mixture was cooled to room temperature, water (10 mL) was added, followed by extraction diluted with ethyl acetate (3 × 10 mL). The combined organic portion was dried with anhydrous Na₂SO₄ and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with a mixture of petroleum ether and ethyl acetate as eluent to afford various target compounds. Compound 4e was obtained in 72% yield (63.2 mg) according to the general procedure as a colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 7.95 (dd, J = 8.0, 1.5 Hz, 1 H), 7.51 (t, J = 7.8 Hz, 1 H), 7.37–7.33 (m, 1 H), 7.27–7.25 (m, 1 H), 7.22 (d, J = 2.7 Hz, 1 H), 7.17 (dd, J = 6.5, 2.4 Hz, 1 H), 7.07–7.03 (m, 2 H), 4.81 (t, J = 7.5 Hz, 1 H), 3.61 (s, 3 H), 2.64 (s, 3 H), 2.31–2.27 (m, 1 H), 2.04–1.99 (m, 1 H), 0.93 (t, J = 7.3 Hz, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 161.66, 140.20, 137.16, 132.75, 130.32, 130.09, 129.58, 126.94, 126.20, 125.72, 123.37, 113.44, 44.29, 29.07, 27.65, 20.05, 12.31. HRMS (ESI-TOF): m/z [M + H]⁺ calcd for C₁₉H₂₀N₂O: 293.1648; found: 293.1641.