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

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

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

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Abstract

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Key words

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

Quinoxalin-2(1H)-one scaffolds exist in many natural products. Due to the significant biological activities and pharmaceutical properties of this structure, such as antitumor,[1] ALR2 inhibition,[2] antibiotic,[3] analgesic,[4] antimicrobial,[5] and aldose reductase inhibition activities (Figure [1]),[6] a range of 3-functionalized quinoxalin-2(1H)-ones has been synthesized, with approaches including arylation,[7] alkylation,[8] etherification,[9] amidation,[10] amination,[11] cyanation,[12] phosphonation,[13] and trifluoromethylation (Scheme [1]).[14]

Figure 1 Pharmaceutically active quinoxalin-2(1H)-one derivatives

Scheme 1 Synthesis of 3-functionalized quinoxalin-2(1H)-one derivatives

Activation of C–H bonds has recently emerged as a powerful method for the construction of C–C bonds.[15] [16] Furthermore, radical addition is a powerful method to form C–C bonds,[17] with the iodide/TBHP system being considered as a dominant protocol in the radical field to achieve C–H bond activation and construction of heterocyclic rings.[18] [19]

Typical approaches for synthesizing 3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-ones involve reaction of aroyl- and hetaroylpyruvic acid or ester derivatives with N-phenyl-o-phenylenediamine (Scheme [2]).[20] [21]

Scheme 2 Synthesis of 3-acetylquinoxalin-2(1H)-one derivatives

As for the synthesis of diverse 3-aryl-quinoxalin-2(1H)-ones, there were two main approaches. One strategy to construct the heterocyclic ring involves two-step acylation of benzene-1,2-diamines with arylglyoxylic acids, followed by subsequent cyclization (Scheme [3], method 1).[7a] Other methods involve direct functionalization. Paul reported the novel Pd(TFA)₂-catalyzed direct dehydrogenative cross-coupling of quinoxalin-2-ones with arenes for the construction of diverse 3-aryl quinoxalin-2-ones (Scheme [3], method 2).[7b] Ramesh reported an oxidative cross-coupling of arylboronic acids with quinoxalin-2-ones using the readily available oxidant Mn(III) acetate dihydrate (Scheme [3], method 3).[7c] Yin’ s group used diaryliodonium tetrafluoroborates at room temperature, with arylhydrazines as the arylating agent (Scheme [3], method 4).[7d] Lee and co-workers reported iodosobenzene-promoted direct arylation with arylhydrazines as radical precursors (Scheme [3], method 5).[7e] However, drawbacks such as the requirement for prefunctionalized substrates, multistep protocols, low atom economy, use of transition-metal catalysts and strong base in these protocols have limited their general application and development. Metal-free systems have replaced tradition metal systems, and iodide or hypervalent iodine possess advantages such as ease of handling, strong electrophilicity, commercial availability, and low toxicity.[22]

Scheme 3 Synthetic approaches to 3-arylquinoxalin-2(1H)-ones

The I₂/TBHP system is a central reagent combination in the radical field.[23] [24] It has been shown that tert-butyl peroxybenzoate (TBPB) is an efficient and highly chemoselective benzoylating reagent.[25,26] In this area, we first disclosed that TBPB could translate into aryl radicals, triggering subsequent reactions, providing a novel method for the introduction of an aryl group.

Herein, we disclose a simple method to synthesize 3-functionalized quinoxalin-2(1H)-ones. In the first part, we present a n-Bu₄NI-catalyzed radical oxidative coupling of acetophenone and quinoxalin-2(1H)-ones using TBHP as oxidant to access 3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-ones. In the second part, the direct arylation of quinoxalin-2(1H)-ones is disclosed. Therein, TBPB is used both as reagent to generate aryl radical and as free radical initiator, while I₂ is used as catalyst (Scheme [4]).

Scheme 4 Studies reported herein

Initially, we chose 1-methylquinoxalin-2-(1H)-one (1a) and acetophenone (2a) as model substrates. The reaction was carried out using 20 mol% of TBAI, 5 equivalents of tert-butyl hydroperoxide (TBHP, 70% solution in water) in DCE at 100 °C. Under these conditions, the desired product 3a was obtained in 32% yield (Table [1], entry 4).

Table 1 Optimization of the Reaction Conditions^a

Entry	[I]/mmol%	[O]/equiv.	Solvent	Temp (°C)	Yield (%)^b
1	I₂/20	TBHP/5	DCE	100	12
2	CuI/20	TBHP/5	DCE	100	24
3	NIS/20	TBHP/5	DCE	100	NR
4	TBAI/20	TBHP/5	DCE	100	32
5	TBAI+I₂/20+10	TBHP/5	DCE	100	23
6	TBAI/10	TBHP/5	DCE	100	8
7	TBAI/100	TBHP/5	DCE	100	12
8	TBAI/20	BPO/5	DCE	100	25
9	TBAI/20	K₂S₂O₈/5	DCE	100	NR
10	TBAI/20	DDQ/5	DCE	100	NR
11	TBAI/20	TBPB/5	DCE	100	30
12^c	TBAI/20	TBHP/5	DCE	100	79
13^c	TBAI/20	TBHP/3	DCE	100	86
14^c	TBAI/20	TBHP/3	dioxane	100	16
15^c	TBAI/20	TBHP/3	DMSO	100	trace
16^c	TBAI/20	TBHP/3	H₂O	100	58
17^c	TBAI/20	TBHP/3	DCE	90	70
18^c	TBAI/20	TBHP/3	DCE	110	67

^a Reaction conditions: 1a (0.3 mmol), 2a (2.0 equiv.), solvent (2 mL), sealed tube, 48 h.

^b Isolated yields.

^c 1a (0.3 mmol), 2a (4.0 equiv.).

Next, we studied a series of iodides and found that using TBAI as catalyst gave higher yields (Table [1], entries 1–7). Then, several oxidants were investigated, such as dibenzoyl peroxide (BPO), tert-butyl peroxybenzoate (TBPB), dibutyl peroxide, K₂S₂O₈, and DDQ, but the reaction with TBHP still resulted in the best result (Table [1], entries 8–11). When we increased the amount of (2a) from 2 equivalents to 4 equivalents and decreased the amount of TBHP from 5 equivalents to 3 equivalents, the yield of target product was increased to 86% (Table [1], entries 12, 13). Finally, other solvents (DMSO, H₂O, 1,4-dioxane, toluene) were studied instead, but unfortunately no improvement in yield was observed (Table [1], entries 14–17). Ultimately, we chose (1a, 0.3 mmol), (2a, 4.0 equiv.), TBAI (20 mol%), and TBHP (3.0 equiv.) in DCE (2 mL) at 100 °C for 48 hours as the optimal reaction conditions.

Unexpectedly, we observed a byproduct in a relatively low yield, with 3-arylquinoxalin-2(1H)-one 4a being observed when BPO or TBPB were used as oxidant. It was observed that reaction with iodine showed a slightly higher yield (Table [2], entry 2). Subsequently, a variety of solvents such as acetonitrile, 1,4-dioxane, and DMSO was investigated (Table [2], entries 6–8). Finally, we surveyed varying the effect of temperature (Table [2], entries 4, 5), but the reaction did not proceed well. In order to confirm the source of the aryl group, we conducted experiments without acetophenone. To our satisfaction, the yield of 4a was increased from 34% to 61% (Table [2], entry 9). Finally, the number of equivalents of iodine and TBPB was investigated, and the yield was eventually improved to 95% (Table [2], entries 10–13). Considering the hazards associated with TBPB, 5 equivalents of TBPB were chosen as the preferred conditions. Thus, the optimized reaction conditions were chosen as TBPB (5 equiv.), I₂ (2 mol%) in DCE at 100 °C for 8 hours.

Table 2 Optimization of the Reaction Conditions^a

Entry	[I]/mmol%	[O]/equiv.	Solvent	Temp (°C)	Yield (%)^b
1	TBAI/20	TBPB/5	DCE	100	30
2	I₂/20	TBPB/5	DCE	100	34
3	KI/20	TBPB/5	DCE	100	33
4	I₂/20	TBPB/5	DCE	90	25
5	I₂/20	TBPB/5	DCE	110	28
6	I₂/20	TBPB/5	CH₃CN	100	38
7	I₂/20	TBPB/5	dioxane	100	41
8	I₂/20	TBPB/5	DMSO	100	NR
9^c	I₂/20	TBPB/5	DCE	100	61
10^c	I₂/50	TBPB/5	DCE	100	27
11^c	I₂/2	TBPB/5	DCE	100	88
12^c	I₂/2	TBPB/4	DCE	100	71
13^c	I₂/2	TBPB/7	DCE	100	95

^a Reaction conditions: 1a (0.3 mmol), 2a (2.0 equiv.), solvent (2.0 mL), sealed tube, 48 h.

^b Isolated yields.

^c Acetophenone was not present.

With the optimized conditions in hand, a range of quinoxalin-2(1H)-ones was investigated to give the corresponding derivatives 3 (Scheme [5]). These N-substituted quinoxalin-2(1H)-one analogues showed good reactivities, giving the anticipated products 3aa–aj in 32–93% yields.

Scheme 5 Substrate scope of quinoxalin-2(1H)-ones. Reagents and conditions: 1 (0.3 mmol), 2a (4.0 equiv.), TBAI (0.2 equiv.), TBHP (3.0 equiv.), DCE (2 mL), sealed tube.[27]

In particular, an N-phenyl-substituted quinoxalin-2(1H)-one was well tolerated, giving the corresponding product 3aj in 64% yield. Likewise, it was found that substrates with N-propyl, N-butyl and N-cyclohexylmethyl substitution provided the desired products (3ag, 3ae, and 3af) in good yields. Then, we explored substitution at R¹ and R² with R³ = CH₃ (Scheme [5]). Electron-donating and electron-withdrawing groups provided the desired products in moderate to good yields (3ak, 3al, and 3an). Subsequently, we found that electron-withdrawing substituents (–F, –Br) had a positive effect compared to an electron-donating group (–CH₃). Furthermore, a substrate with an additional aromatic ring resulted a high yield of 73% (3am).

Finally, we studied the scope of acetophenones (Scheme [6]). When the substrates possessed electron-donating groups, the yields were lower with a substituent at the ortho position than at the para position. In addition, o-hydroxyacetophenone also gave the desired product 3ba in 57%. yield. With electron-withdrawing groups present at the ortho or para positions, the corresponding products 3bb–bi were obtained in 33–74% yields. The π-extended aromatic substrate provided the expected product 3bj in a 78% yield.

Scheme 6 Substrate scope of quinoxalin-2(1H)-ones. Reagents and conditions: 1a (0.3 mmol), 2 (4.0 equiv.), TBAI (0.2 equiv.), TBHP (3.0 equiv.), DCE (2 mL), sealed tube.[27]

Most of the substrates studied gave the expected products 4aa–ai in moderate to excellent yields (Scheme [7]). N-Substituted quinoxalin-2(1H)-ones containing N-ester, N-benzyl, N-benzene acetyl, N-propyl, and N-aryl substituents were all suitable for this reaction, providing the desired products in moderate to good yields. In addition, N-phenyl quinoxalinone gave the corresponding product 4af in 94% yield. Finally, we explored substitutions at R¹ and R² with R³ = CH₃. An electron-withdrawing substituent (–Cl) had a positive effect compared to an electron-donating group (–CH₃). Appending an additional aromatic ring also led to 4ai in 70% yield (Scheme [7]).

Scheme 7 Substrate scope of quinoxalin-2(1H)-ones. Reagents and conditions: 1a (0.3 mmol), I₂ (0.02 equiv.), TBPB (5.0 equiv.), solvent (2.0 mL), sealed tube.[27]

Addition of a radical-trapping reagent such as 2,2,6,6-tetramethylpiperidine N-oxide (TEMPO) or BHT to the reaction suppressed the transformation, strongly indicating that the C–C bond formation is a radical-mediated process (Scheme [8]).

Scheme 8 Experiments with added radical inhibitors

On the basis of this result, a plausible reaction mechanism can be proposed (Scheme [9]). Either the tert-butoxy radical or tert-butylhydroperoxy radical can remove a hydrogen atom from 2a to form radical intermediate 5. Addition of intermediate 5 to 1a affords intermediate 6. Then intermediate 6 can undergo 1,2-H shift to form the more stable intermediate 7. Finally, the final product 3a is obtained by hydrogen-atom removal by a tert-butoxy radical.

Scheme 9 Plausible reaction mechanism

For the TBPB reaction catalyzed by I₂, the benzoyl radical releases carbon dioxide forming the phenyl radical under standard conditions. Addition of the phenyl radical to the carbon–nitrogen double bond affords radical intermediate 10, which is further oxidized by the iodide cation to form nitrogen cation compound 11 that then undergoes 1,2-H shift to give 12. Finally, the desired compound is obtained by hydrogen-atom removal to give 4a (Scheme [10]).

Scheme 10 Plausible reaction mechanism

In conclusion, we have developed a novel protocol for direct synthesis of 3-(2-oxo-2-phenylethylidene)-3,4-dihydroquinoxalin-2(1H)-ones.[] The iodide/peroxide system has been shown to be a powerful combination to activate the C–H bond of quinoxalin-2(1H)-ones. This process exhibits good functional group tolerance with a broad substrate scope, resulting in acetylation of quinoxalin-2(1H)-ones and providing a new method for the introduction of an aryl group.

References

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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

Figures

Figure 1 Pharmaceutically active quinoxalin-2(1H)-one derivatives

Scheme 1 Synthesis of 3-functionalized quinoxalin-2(1H)-one derivatives

Scheme 2 Synthesis of 3-acetylquinoxalin-2(1H)-one derivatives

Scheme 3 Synthetic approaches to 3-arylquinoxalin-2(1H)-ones

Scheme 4 Studies reported herein

Scheme 5 Substrate scope of quinoxalin-2(1H)-ones. Reagents and conditions: 1 (0.3 mmol), 2a (4.0 equiv.), TBAI (0.2 equiv.), TBHP (3.0 equiv.), DCE (2 mL), sealed tube.[27]

Scheme 6 Substrate scope of quinoxalin-2(1H)-ones. Reagents and conditions: 1a (0.3 mmol), 2 (4.0 equiv.), TBAI (0.2 equiv.), TBHP (3.0 equiv.), DCE (2 mL), sealed tube.[27]

Scheme 7 Substrate scope of quinoxalin-2(1H)-ones. Reagents and conditions: 1a (0.3 mmol), I₂ (0.02 equiv.), TBPB (5.0 equiv.), solvent (2.0 mL), sealed tube.[27]

Scheme 8 Experiments with added radical inhibitors

Scheme 9 Plausible reaction mechanism

Scheme 10 Plausible reaction mechanism

Supplementary Material

Supporting Information