One-step approach for the synthesis of functionalized quinoxalines mediated by T3P®–DMSO or T3P® via a tandem oxidation–condensation or condensation reaction

Abstract

An easy and efficient propylphosphonic anhydride (T3P®)–DMSO or T3P® mediated oxidation–condensation or condensation reaction for the synthesis of quinoxalines derived from the interaction of different arrays of condensing partners with ortho-phenylene diamines (o-PDs) under simple and mild reaction conditions in one step has been reported for the first time.

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Introduction

New synthetic organic transformations for the synthesis of functionalized N-containing heterocyclic small molecules from simple starting materials are of great importance in the field of synthetic organic chemistry. Quinoxalines, or benzopyrazines, in particular have been studied for their antibacterial, antiviral, anthelmintic, antiinflammatory, kinase inhibitory and anticancer activities¹ and they also have a wide array of other applications.² In addition, the quinoxaline nucleus is contained in some important antibiotics such as olaquindox, carbadox, echinomycin, levomycin and actinoleutin. Owing to their wide ranging biological activity and for technical interest, a number of synthetic strategies have been developed for the synthesis of various substituted quinoxalines. Out of these methods of synthesis, oxidation–condensation and condensation reactions are major synthetic steps used for the synthesis of the bioactive quinoxaline nucleus from readily available precursors like o-PDs and α-hydroxy ketones.³ In addition, several other methods are also available for the synthesis of quinoxalines from the reaction of phenacyl bromides,⁴ 1,2-diketones,⁵ alkynes,⁶ epoxides,⁷ and arylimino oximes⁸ with o-PDs.

Most of the methods reported above suffer from one or more disadvantages such as poor substrate scope, harsh reaction conditions, laborious and complex work-up procedures, expensive and moisture sensitive reagents, undesirable side products and unsatisfactory yields. During the course of a recent investigation, our research group found that T3P® (propylphosphonic anhydride) can be used in the synthesis of peptides,⁹ as well as the synthesis of polysubstituted quinolines and naphthyridines,¹⁰ β-lactams,¹¹ pyrimidinones using the Biginelli reaction,¹² 1,2,4-oxadiazoles, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles¹³ and Fischer indoles.¹⁴ Due to T3P®’s significant properties as a water scavenger in oxidation–cyclization reactions, we recently reported several one-pot tandem approaches for the synthesis of benzimidazoles and benzothiazoles,^15a as well as 4-thiazolidinones^15b and imidazo[1,2-a]pyridines^15c from alcohols, using DMSO–propylphosphonic anhydride (T3P®) as an oxidizing medium as well as a cyclodehydrating agent. As a continuation of our research into the synthesis of heterocycles,¹⁶ we report, herein, a new strategic one-step method for the synthesis of quinoxalines from the reaction of α-hydroxy ketones, α-halo ketones and 1,2-diketones with o-PDs using DMSO–propylphosphonic anhydride (T3P®) or propylphosphonic anhydride (T3P®) in ethyl acetate (EtOAc) at room temperature. The reaction occurred either via an oxidation followed by condensation or a simple condensation reaction. To optimize the reaction conditions, we initially selected the reaction between o-PD 1a and 2-hydroxy-1,2-diphenylethanone 2a (Scheme 1) in a mixed solvent of EtOAc : DMSO (ratio 2 : 1) followed by the addition of 1 equivalent of T3P® (50% solution in EtOAc) under stirring at 0 °C, then RT for 10 h, which afforded the desired 2,3-diphenylquinoxaline 3e in 25% yield. For the same reaction we checked if different equivalents of T3P® could affect the course of the reaction and the yield of 3e. Therefore, we carried out the oxidation–condensation using various equivalents of T3P®. The best result was obtained when the reaction between 1,2-diphenylethanone and o-PD was carried out with 2.0 equivalents of T3P® in the presence of DMSO and stirred at RT for 6 h. We also studied the reaction by keeping the equivalent of T3P® (2.0 eq.) constant and varying both the temperature and time. Notably, we were not able to achieve a greater percentage yield compared to the yield obtained at RT conditions. The optimization results are summarized in Table 1. Thus, a clear optimization of the reaction conditions to obtain quinoxalines from a α-hydroxyl ketone with o-PD was revealed from our studies, which involved using 2.0 equivalents of T3P® and stirring the reaction mixture at 0 °C then RT for 6 h. The product was isolated by initially washing the reaction mixture with water followed by brine, then purified by column chromatography using 60–120 silica gel. The oxidation–condensation or cyclodehydrating properties of T3P® helped to generalize the reaction procedure. Next, we carried out reactions with a series of electronically diverse α-hydroxy ketones and o-PDs mediated by T3P® in a solvent mixture of DMSO : EtOAc in order to obtain the desired quinoxalines 3a–k. The o-PD and α-hydroxy ketone without any substitution afforded a good yield of product, while the α-hydroxy ketone containing an electron-donating group favoured the formation of the desired quinoxalines in high yields, when compared to reactions where o-PD contained an electron-withdrawing group. These results are summarized in Scheme 2. The scope of the reaction was successfully extended to other substrates such as electronically demanding α-bromo ketones with o-PD or substituted o-PDs, which also underwent the title reaction under RT conditions to obtain the corresponding quinoxalines (4a–y). Similarly, the reaction of an α-halo ketone and o-PD without any substitution favoured the formation of a quinoxaline in slightly higher yield when compared to reactions using substituted α-halo ketones or o-PDs. These results are summarized in Scheme 3. We then extended our studies to further increase the substrate scope. We carried out the condensation of 1,2-dicarbonyl compounds with o-PD under mild reaction conditions at RT in the presence of T3P® to produce the desired quinoxaline derivatives (5a–p). Interestingly, the reaction between an aliphatic diketone and o-PD underwent the title reaction to afford the desired quinoxaline in lower yield when compared to aromatic 1,2-diketones. In the case where both aromatic starting materials were without substitution, the reaction favoured the formation of the quinoxaline in the highest yield. These results are summarized in Scheme 4.

Scheme 1 The synthesis of a 2,3-diphenyl quinoxaline (3e) from an α-hydroxy ketone.

Table 1 The T3P®–DMSO mediated synthesis of 3e under different reaction conditions

Entry	Solvent^a	T3P®^b (equiv.)	Time (h)	T [°C]	Yield^c (%) of 3e
a Reactions were performed with the solvent and DMSO in a volume ratio of 2 : 1. 1 mmol of 1a, 1.2 mmol of 2a were used in the case of 3e.b T3P® (50% solution in EtOAc) was used to carry out the reactions.c Isolated yield after purification by column chromatography.
1	EtOAc	1.0	10	0–25	25
2	EtOAc	1.5	6	0–25	54
3	EtOAc	2.0	6	0–25	94
4	EtOAc	2.5	6	0–25	94
5	EtOAc	3.0	6	0–25	93
6	EtOAc	3.5	6	0–25	93
7	CH2Cl2	2.5	6	0–25	48
8	CHCl3	2.5	6	0–25	44
9	CH3CN	2.5	6	0–25	55
10	THF	2.5	6	0–25	49
11	Toluene	2.5	6	0–25	58
12	Dioxane	2.5	6	0–25	56
13	Benzene	2.5	6	0–25	40
14	EtOAc	2.5	5.5	50	87
15	EtOAc	2.5	5	60	86
16	EtOAc	2.5	4	65	88
17	EtOAc	2.5	3	75	80

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Scheme 2 The synthesis of quinoxalines from α-hydroxy ketones. T3P® (2.0 mmol), α-hydroxy ketone (1.2 mmol), 1,2 diamine (1.0 mmol).

Scheme 3 The synthesis of quinoxalines from an α-halo ketone. T3P® (2.0 mmol), α-bromo ketone (1.2 mmol), diamine (1.0 mmol). ^dA mixture of regioisomers.

Scheme 4 The synthesis of quinoxalines from 1,2-diketones. T3P® (2.0 mmol), 1,2-diketone (1.2 mmol), diamine (1.0 mol).

Selected quinoxaline compounds from Schemes 1 and 3, including 3k, 4o, 4p, 4q, 4r, 4s, 4t, 4u, 4v, 4w and 4x, were evaluated as cytotoxic agents against A549 human lung carcinoma cells, which have frequently been chosen by our group,¹⁷ as a suitable cell culture to perform cytotoxicity assays. Concentration–response experiments were performed to establish the cytotoxic activity of each selected compound (Fig. 1).

Fig. 1 Bar graphs showing cytotoxic activity of different quinoxalines towards the A549 cell line.

We observed that quinoxalines 3k, 4o, 4s, 4v and 4u were the most efficient cytotoxic agents when a high concentration (25 μM) was used, resulting in the death of 74% of the A549 cells in case of 4o. The IC₅₀ values, expressed in μM, are summarized in Table 2 and establish the relative order of cytotoxic effectiveness for the quinoxalines as: 3k ≈ 4o > 4s > 4v > 4u > 4q > 4r > 4t > 4p > 4x > 4w. From these results we can conclude that the slight differences in the observed cytotoxicity might be due to differences in the nature of the substituents present in the core moiety and the percentage uptake of the compounds by the cells (Scheme 5).

Table 2 IC₅₀ (μM) inhibitory concentrations with human lung carcinoma cells (A549)

Quinoxaline	3k	4o	4p	4q	4r	4s	4t	4u	4v	4w	4x
IC50 (μM)	2.14	2.11	27.3	17.4	19.4	2.8	20.3	10.3	5.3	33.2	30.3

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Scheme 5 Proposed mechanism for the formation of quinoxalines in Scheme 1.

Conclusion

This synthetic methodology provides a versatile, one-step protocol for the preparation of libraries of quinoxalines with broad substrate scope and in high yield. Preliminary investigations into the cytotoxic effects of the studied quinoxaline compounds against A-549 cancer cells showed that the lowest IC₅₀ values were observed with phenyl substituted o-PD derived quinoxaline 3k and phenyl substituted α-halo ketone derived quinoxaline 4o. These promising results show that the application of DMSO–T3P® or T3P® mediated reactions can open access to new chemical space in the field of synthetic organic chemistry and also allow the exploration of new synthetic strategies for the synthesis of biologically active heterocyclic small molecules in the field of medicinal chemistry.

Fig. 2 Single crystal XRD structure of compound 4y.

Experimental section

Materials and instruments

Purification of the reaction products was carried out by normal column chromatography using Sorbent Technologies Standard Grade silica gel (60–120 mesh). Analytical thin layer chromatography was performed on Merck silica gel 60 F₂₅₄ plates. Visualization was accomplished with UV light and potassium permanganate. Melting points were recorded on a Thomas Hoover capillary melting point apparatus and are uncorrected. Infrared spectra were recorded on an ATI Mattson Genesis Series FT-infrared spectrophotometer. Proton nuclear magnetic resonance spectra (¹HNMR) were recorded on an Agilent 400 MHz spectrometer and are reported in ppm using CDCl₃ as the internal standard (7.24 ppm). Proton-decoupled carbon nuclear magnetic resonance spectra (¹³C-NMR) were recorded on a Agilent 100 MHz spectrometer and reported in ppm using CDCl₃ as the internal standard (77.0 ppm). Mass spectra were recorded on a Waters instrument, column – BEH C18 1.7 μM 2.1 × 50 mm; solvents – 0.1% formic acid in water (a) and CH₃CN (b) with a solvent gradient-varied concentration of solvent (a) and (b) at different time intervals; detector – MS detector. Elemental analyses were recorded using a HERAEUS Vario EL-III instrument (for CHN).

General procedure for the synthesis of quinoxalines from α-hydroxy ketones

To a stirred suspension of α-hydroxy ketone (1.2 mmol) in a solvent mixture of DMSO : EtOAc (ratio 2 : 1) was added ortho-phenylenediamine (1 mmol). This was followed by the addition of T3P® (2.0 mmol) at 0 °C, then the reaction mixture was kept at RT for 6 h. The progress of the reaction was monitored by TLC. The reaction mixture was quenched with ice cold water and the reaction mixture was extracted with EtOAc (×2). The collected organic layers were washed with brine solution and dried over anhydrous sodium sulphate. The organic solvent was removed under reduced pressure to afford the desired quinoxaline, which was purified by column chromatography using hexanes : EtOAc as an eluent.

General procedure for the synthesis of quinoxalines from α-haloketone and 1,2-diketone

To a stirred reaction mixture of an α-bromo ketone or 1,2-diketone (1.2 mmol) in EtOAc was added ortho-phenylenediamine (1 mmol) followed by the addition of T3P® (2 mmol) at 0 °C. The reaction mixture was then kept at RT for 5 h. The progress of the reaction was monitored by TLC. The reaction mixture was quenched with ice cold water and the reaction mixture was extracted with EtOAc (×2). The collected organic layers were washed with brine solution and dried over anhydrous sodium sulphate. The organic solvent was removed under reduced pressure to afford the desired quinoxalines, which were purified by column chromatography using hexanes : EtOAc as an eluent.

2-Phenylquinoxaline (3a or 4a) 18a. Pale yellow solid; yield 95%; (Rf = 0.48 in hexanes/EtOAc 95 : 05 v/v); MP 75–77 °C (Lit: 75–78);^18c IR (KBr): 3055, 1545, 1480, 1445, 1312, 1035 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.33 (s, 1H), 8.21–8.11 (m, 4H), 7.81–7.73 (m, 2H), 7.59–7.52 (m, 3H); LCMS (ESI) [M + H]⁺ calculated C₁₄H₁₀N₂ 207.0877 found 207.14.

2-(p-Tolyl)quinoxaline (3b). Yellow solid; yield 94%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 92–94 °C (Lit: 91–93);^18a IR (KBr): 3058, 1615, 1554, 1475, 1445, 1310, 1040 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.40 (s, 1H), 8.55–8.38 (m, 4H), 8.37–8.20 (m, 2H), 7.88 (d, J = 8 Hz, 2H), 2.40 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₁₅H₁₂N₂ 221.10 found 221.16.

6,7-Dimethyl-2-phenylquinoxaline (3c or 4m). Yellow solid; yield 92%; (Rf = 0.54 in hexanes/EtOAc 95 : 05 v/v); MP 129–130 °C (Lit: 130–131);^18a IR (KBr): 3055, 3040, 2965, 1535, 1480, 1445, 1310, 1210, 1020, 1005 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.22 (s, 1H), 8.20 (d, J = 11.2 Hz, 2H), 7.89 (s, 1H), 7.88 (s, 1H), 7.65–7.36 (m, 3H), 3.41 (s, 6H); LCMS (ESI) [M + H]⁺ calculated C₁₆H₁₄N₂ 235.11 found 235.18.

6,7-Dimethyl-2-(p-tolyl)quinoxaline (3d). Yellow solid; yield 92%; (Rf = 0.62 in hexanes/EtOAc 95 : 05 v/v); MP 113–115 °C; (Lit: 114–115);^18h IR (KBr): 3025, 2973, 1605, 1530, 1480, 1442, 1315, 1045, 1025, 860, 825 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.36 (s, 1H), 8.13 (d, J = 7.2 Hz, 2H), 8.12 (s, 1H), 7.82 (s, 1H), 7.81 (s, 1H), 7.09 (d, J = 8 Hz, 2H), 2.63 (s, 3H), 2.33 (s, 6H); LCMS (ESI) [M + H]⁺ calculated C₁₇H₁₆N₂ 249.13 found 249.19.

2,3-Diphenylquinoxaline (3e or 5a). Yellow solid; yield 94%; (Rf = 0.58 in hexanes/EtOAc 95 : 05 v/v); MP 116–118 °C; (Lit: 117–119);^18a IR (KBr): 3056, 1635, 1475, 1440, 1345, 1075, 1055, 770, 695 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.18 (dd, J = 6.8 Hz, 3.2 Hz, 2H), 7.77 (dd, J = 3.6 Hz, 3.2 Hz, 2H), 7.53–7.50 (m, 4H), 7.38–7.31 (m, 6H); LCMS (ESI) [M + H]⁺ calculated C₂₀H₁₄N₂ 283.12 found 283.18.

2-Phenyl-3-p-tolylquinoxaline (3f or 5c). Yellow solid; yield 93%; (Rf = 0.62 in hexanes/EtOAc 95 : 05 v/v); MP 110–112 °C; (Lit: 112–114);^18a IR (KBr): 3055, 2915, 1614, 1553, 1519, 1470, 1438, 1388, 1345, 1056, 1020, 974, 754, 696 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.26–8.14 (m, 2H), 7.99–7.95 (m, 2H), 7.83–7.78 (m, 2H), 7.72 (d, J = 7.6 Hz, 2H), 7.69–7.40 (m, 3H), 7.13 (d, J = 6.8 Hz, 2H), 2.42 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₂₁H₁₆N₂ 297.13 found 297.20.

6-Methyl-2,3-diphenylquinoxaline (3g or 5g). White solid; yield 92%; (Rf = 0.54 in hexanes/EtOAc 95 : 05 v/v); MP 111–113 °C; (Lit: 110–112);^18a IR (KBr): 3054, 2938, 1617, 1485, 1444, 1200, 1056, 1021, 812, 768, 698 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.10 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 7.92 (dd, J = 9.6 Hz, 1.6 Hz, 1H), 7.78–7.69 (m, 4H), 7.68–7.31 (m, 6H), 2.77 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₂₁H₁₆N₂ 297.13 found 297.19.

6-Methoxy-2,3-diphenylquinoxaline (3h or 5i). White solid; yield 92%; (Rf = 0.52 in hexanes/EtOAc 95 : 05 v/v); MP 160–162 °C; (Lit: 117–119);^18a IR (KBr): 2965, 2936, 1756, 1617, 1482 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.04 (d, J = 8.8 Hz, 1H), 7.95–7.92 (m, 4H), 7.91 (d, J = 2 Hz, 1H), 7.59 (dd, J = 9.2 Hz, 2.8 Hz, 1H), 7.37–7.34 (m, 6H), 3.83 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₂₁H₁₆N₂O 313.12 found 313.18.

6-Bromo-2,3-diphenylquinoxaline (3i or 5j). Yellow solid; yield 94%; (Rf = 0.48 in hexanes/EtOAc 95 : 05 v/v); MP 117–119 °C; (Lit: 118–120);^18a IR (KBr); 3040, 1588, 1542, 1466, 1442, 1390, 1318, 1182, 1060, 1022, 973, 914, 828, 764, 694 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.35 (s, 1H), 8.03 (d, J = 9.2 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 6.8 Hz, 4H), 7.39–7.31 (m, 6H); LCMS (ESI) [M + H]⁺ calculated C₂₀H₁₃BrN₂ 361.03 found 361.09.

6-Chloro-2,3-diphenylquinoxaline (3j or 5l). White solid; yield 80%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 118–120 °C; (Lit: 117–120);^18a IR (KBr): 3047, 1602, 1548, 1464, 1442, 1338, 1068, 828, 800, 764, 694 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ = 7.96 (d, J = 8.4 Hz, 1H), 7.90–7.64 (m, 5H), 7.60–7.34 (m. 6H), 2.77 (s, 3H), 2.48 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₂₁H₁₆N₂ 317.08 found 317.14.

2,3-Di(furan-2-yl)-6-phenylquinoxaline (3k or 5o). White solid; yield 91%; (Rf = 0.55 in hexanes/EtOAc 95 : 05 v/v); MP 131–133 °C; IR (KBr): 3356, 1614, 1538, 1438, 1081, 835, ¹H NMR (CDCl₃, 400 MHz): δ = 8.31 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.94 (t, J = 4 Hz, 1H), 7.92 (t, J = 3.6 Hz, 1H), 7.65–7.64 (m, 2H), 7.59 (dd, J = 7.2 Hz, 2.8 Hz, 2H), 7.39–7.34 (m, 1H), 7.17 (t, J = 9.6 Hz, 1H), 6.72–6.69 (m, 2H), 6.59–6.58 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ = 144.9, 144.4, 130.6, 130.3, 129.6, 129.3, 128.0, 127.2, 126.2, 113.6, 113.2, 112.1; LCMS (ESI) [M + H]⁺ calculated C₂₂H₁₄N₂O₂ 339.10 found 339.17; anal. calcd for C₂₁H₁₆N₂: C, 78.09; H, 4.17; N, 8.28; found: C, 77.78; H, 3.97; N, 7.96.

(Naphthalen-2-yl)quinoxaline (4b). Yellow solid; yield 94%; (Rf = 0.60 in hexanes/EtOAc 95 : 05 v/v); MP 136–138 °C; (Lit: 138);^18a IR (KBr): 3038, 1546, 1488, 1306, 1196 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.47 (s, 1H), 8.65 (s, 1H), 8.37–8.34 (dd, J = 10.8 Hz, 2 Hz, 1H), 8.21–8.13 (m, 2H), 8.03–7.99 (m, 2H), 7.90 (t, J = 3.6 Hz, 1H), 7.82–7.73 (m, 2H), 7.54–7.50 (m, 2H); LCMS (ESI) [M + H]⁺ calculated C₁₈H₁₂N₂ 257.10 found 257.17.

2-(m-Tolyl)quinoxaline (4c). Yellow solid; yield 94%; (Rf = 0.52 in hexanes/EtOAc 95 : 05 v/v); MP 92–94 °C; (Lit: 84–86);^18f IR (KBr): 3054, 1612, 1542, 1308 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.33 (s, 1H), 8.19–8.13 (m, 2H), 8.04 (s, 1H), 7.97 (d, J = 8 Hz, 1H), 7.98–7.75 (m, 2H), 7.47 (t, J = 8 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 2.51 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₁₅H₁₂N₂ 221.10 found 221.17.

2-(3-Methoxyphenyl)quinoxaline (4d). Pale yellow solid; yield 92%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 96–98 °C; (Lit: 87–88);^18h IR (KBr): 1604, 1539, 1442, 1186, 1031 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.32 (s, 1H), 8.18–8.11 (m, 2H), 7.81–7.73 (m, 4H), 7.47 (t, J = 8 Hz, 1H), 7.07 (dd, J = 10.4 Hz, 2 Hz, 1H), 3.94 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₁₅H₁₂N₂O 237.09 found 237.15.

2-(4-Bromophenyl)quinoxaline (4e). Pale yellow solid; yield 94%; (Rf = 0.56 in hexanes/EtOAc 95 : 05 v/v); MP 136–138 °C; (Lit: 134–137);^18a IR (KBr): 1588, 1536, 1480, 1122, 1068, 1043 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.29 (s, 1H), 8.15–8.07 (m, 4H), 7.81–7.73 (m, 2H), 7.69 (d, J = 8.4 Hz, 2H); LCMS (ESI) [M + H]⁺ calculated C₁₄H₁₀BrN₂O 285.00 found 284.79.

2-(3,4-Dichlorophenyl)quinoxaline (4f). Yellow solid; yield 90%; (Rf = 0.58 in hexanes/EtOAc 95 : 05 v/v); MP 186–188 °C; (Lit: 187–189);^18a IR (KBr): 1540, 1474, 1308, 1146, 1030 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.31 (s, 1H), 8.43 (s, 1H), 8.09 (t, J = 6 Hz, 2H), 7.80 (d, J = 7.2 Hz, 1H), 7.80–7.72 (m, 2H); LCMS (ESI) [M + H]⁺ calculated C₁₄H₉Cl₂N₂ 275.01 found 275.07.

2-(4-Nitrophenyl)quinoxaline (4g). Colorless solid; yield 92%; (Rf = 0.64 in hexanes/EtOAc 95 : 05 v/v); MP 191–193 °C; (Lit: 190–192);^18a IR (KBr): 3056, 1529, 1352, 1096 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.11 (s, 1H), 8.40–8.37 (m, 4H), 8.21–7.84 (m, 2H), 7.83 (d, J = 8 Hz, 2H); LCMS (ESI) [M + H]⁺ calculated C₁₄H₉N₃O₂ 252.07 found 252.13.

4-(Quinoxalin-2-yl)benzonitrile (4h). Pale yellow solid; yield 93%; (Rf = 0.60 in hexanes/EtOAc 95 : 05 v/v); MP 114–116 °C; (Lit: 193–195); IR (KBr): 3058, 2230, 1548, 1480, 1435, 1322, 1036; ¹H NMR (CDCl₃, 400 MHz): δ = 9.36 (s, 1H), 8.35 (d, J = 8.8 Hz, 2H), 8.19–8.15 (m, 2H), 7.88–7.80 (m, 4H); ¹³C NMR (CDCl₃, 100 MHz): δ = 143.0, 142.6, 142.3, 141.7, 140.6, 133.0, 131.8, 130.5, 129.6, 129.1, 128.2, 127.7, 118.8, 113.8; LCMS (ESI) [M + H]⁺ calculated C₁₅H₉N₃ 232.08 found 232.14. Anal. calcd for C₁₅H₉N₃: C, 77.91; H, 3.92; N, 18.17; found: C, 77.61, H, 3.56, N; 17.98.

2-(4-(Trifluoromethyl)phenyl)quinoxaline (4i). Pale yellow solid; yield 92%; (Rf = 0.40 in hexanes/EtOAc 95 : 05 v/v); MP 142–143 °C; (Lit: 142–143);¹⁸ⁱ IR (KBr): 3036, 1545, 1488, 1315, 1120, 645, 554 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.33 (s, 1H), 8.31 (d, J = 8.4 Hz, 2H), 8.12–8.10 (m, 2H), 7.88–7.76 (m, 4H); LCMS (ESI) [M + H]⁺ calculated C₁₅H₁₀N₂F₃ 275.07 found 275.14.

2-(Pyridin-3-yl)quinoxaline (4j). White solid; yield 90%; (Rf = 0.44 in hexanes/EtOAc 95 : 05 v/v); MP 110–112 °C; (Lit: 114–115);^18j IR (KBr): 3052, 1612, 1588, 1542, 1491, 1370, 1025, 1312; ¹H NMR (CDCl₃, 400 MHz): δ = 9.35 (s, 1H), 9.34 (s, 1H), 8.77 (dd, J = 6 Hz, 1.2 Hz, 1H), 8.54 (dt, J = 12.4 Hz, 2 Hz, 1H), 8.20–8.12 (m, 2H), 7.85–7.77 (m, 2H), 7.53–7.50 (m, 1H); LCMS (ESI) [M + H]⁺ calculated C₁₃H₉N₃ 208.08 found 208.14.

2-(Thiophen-2-yl)quinoxaline (4k). Pale yellow solid; yield 94%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 116–118 °C; (Lit: 116–117);^18a IR (KBr): 3120, 3056, 1546, 1424, 1328, 1052 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.16 (s, 1H), 8.08–7.87 (m, 2H), 7.78–7.68 (m, 3H), 7.58 (d, J = 4 Hz, 1H), 7.56 (dd, J = 6.4 Hz, 1.6 Hz, 1H); LCMS (ESI) [M + H]⁺ calculated C₁₂H₉N₂S 213.04 found 213.10.

2-(Furan-2-yl)quinoxaline (4l). Pale yellow solid; yield 93%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 131–133 °C; (Lit: 131–136);^18a IR (KBr): 3134, 3118, 1608, 1548, 1444, 1296, 1225, 1126, 1080 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.25 (s, 1H), 8.11–8.06 (m, 2H), 7.78–7.68 (m, 3H), 7.31 (d, J = 4 Hz, 1H), 6.63 (dd, J = 4.8 Hz, 1.2 Hz, 1H); LCMS (ESI) [M + H]⁺ calculated C₁₂H₈N₂O 197.06 found 197.12.

6-Bromo-2-(pyridin-3-yl)quinoxaline (regioisomers) (4n). A mixture of two regioisomers, which were not separable by column chromatography, was obtained as a white solid. The NMR spectra indicated that 4n was a mixture. The NMR spectra indicated that it is a mixture. White solid; yield 92%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); IR (KBr): 3066, 1608, 1548, 1490, 1318, 648 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.46 (s, 1H), 9.38 (s, 1H), 8.83 (s, 1H), 8.57–8.56 (t, J = 3.6 Hz, 1H), 8.36 (t, J = 2 Hz, 1H), 8.08–8.03 (m, 1H), 7.94–7.88 (m, 1H), 7.58–7.54 (m, 1H) LCMS (ESI) [M + H]⁺ calculated 285.99 found 286.05.

2-([1,1′-Biphenyl]-4-yl)quinoxaline (4o). Colorless solid; yield 95%; (Rf = 0.44 in hexanes/EtOAc 95 : 05 v/v); MP 132–134 °C; (130–133);^18a IR (KBr): 3060, 1534, 1486, 1420, 1317, 1054 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.38 (s, 1H), 8.33 (d, J = 8 Hz, 2H), 8.19–8.13 (m, 2H), 7.95 (t, J = 6.4 Hz, 2H), 7.83–7.75 (m, 2H), 7.69 (t, J = 7.6 Hz, 1H), 7.47–7.40 (m, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ = 150.99, 142.96, 142.36, 141.81, 141.57, 14.50, 140.67, 136.70, 132.19, 130.72, 130.47, 130.01, 129.63, 129.04, 128.24, 127.90, 126.43, 125.83, 121.04, 119.17; LCMS (ESI) [M + H]⁺ calculated C₂₀H₁₄N₂ 283.11 found 283.17.

2-(2′-Methylbiphenyl-4-yl)quinoxaline (4p). White solid; yield 94%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 128–130 °C; IR (KBr): 3065, 2910, 1560, 1480, 1415, 1312, 1052 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.39 (s, 1H), 8.26 (dd, J = 2 Hz, 8.4 Hz, 2H), 8.19–8.13 (m, 2H), 7.83–7.75 (m, 2H), 7.55 (d, J = 8 Hz, 2H), 7.32–7.29 (m, 4H), 2.34 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ = 151.7, 144.0, 143.3, 141.5, 141.0, 135.3, 135.2, 130.5, 130.1, 129.6, 129.5, 129.1, 127.6, 127.3, 125.9, 20.5; anal. calcd for C₂₁H₁₆N₂: C, 85.11; H, 5.44; N, 9.45. Found: C, 84.90; H, 5.06; N, 9.38.

2-(5′-Fluoro-2′-methoxybiphenyl-4yl)quinoxaline (4q). White solid; yield 92%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 134–136 °C; IR (KBr): 3058, 2858, 1528, 1482, 1418, 1145, 1315, 1052, 686 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.38 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 8.19–8.12 (m, 2H), 7.82–7.77 (m, 2H), 7.76–7.72 (m, 2H), 7.13 (dd, J = 2.8 Hz, 8.8 Hz, 1H), 7.07–6.93 (m, 2H), 3.8 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ = 158.3, 155.9, 152.7, 151.5, 143.3, 142.3, 141.5, 139.4, 135.6, 130.3, 130.1, 129.6, 129.5, 129.1, 127.2, 56.2; anal. calcd for C₂₁H₁₆N₂: C, 76.35; H, 4.58; N, 8.48; found: C, 75.92, H, 4.66, N, 8.38.

2-(2′-Ethoxy-4′-fluoro-[1,1′-biphenyl]-4-yl)quinoxaline (4r). White solid; yield 92%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 136–138 °C; IR (KBr): 3052, 2890, 1532, 1483, 1427, 1319, 1055, 812 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.37 (s, 1H), 8.18 (d, J = 1.6 Hz, 1H), 8.15 (d, J = 6.8 Hz, 2H), 8.14–8.05 (m, 2H), 8.04 (d, J = 8 Hz, 2H), 7.81–7.31 (m, 3H), 7.05 (dd, J = 11.6 Hz, 2.8 Hz, 1H), 3.99 (q, J = 16 Hz, 7.2 Hz, 2H), 1.58 (t, J = 7.2 Hz, 3H); ¹³C NMR (CDCl₃, 100 MHz); 157.47, 152.02, 141.81, 141.57, 140.67, 136.50, 132.29, 130.89, 130.47, 129.04, 128.24, 127.90, 126.53, 125.73, 121.04, 114.27, 110.08, 68.64, 15.47; anal. calcd for C₂₂H₁₇FN₂O: C, 76.73; H, 4.98; N, 8.13; found: C, 76.33, H, 4.88, N, 7.98.

2-(2′-Chloro-[1,1′-biphenyl]-4-yl)quinoxaline (4s). White solid; yield 93%; (Rf = 0.50 in hexanes/EtOAc 95 : 05 v/v); MP 133–135 °C; IR (KBr): 3052, 1528, 1480, 1476, 1416, 1312, 1051, 748 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.37 (s, 1H), 8.27 (d, J = 12 Hz, 2H), 8.17–8.11 (m, 2H), 7.77 (m, 2H), 7.65 (d, J = 8 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H), 7.40–7.29 (m, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ = 151.4, 143.2, 142.3, 141.6, 141.3, 139.7, 136.0, 132.5, 131.2, 130.2, 130.0, 129.6, 129.5, 129.1, 128.9, 127.2, 126.9; anal. calcd for C₂₀H₁₃ClN₂: C, 75.83; H, 4.14; N, 8.84 found: C, 74.82, H, 4.08, N, 8.92.

2-(2′-Chloro-5′-fluorobiphenyl-4-yl)quinoxaline (4t). White solid; yield 90%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 141–143 °C; IR (KBr): 3060, 1532, 1484, 1416, 1316, 1050, 734, 688 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.37 (s, 1H), 8.26 (dd, J = 2 Hz, 8.8 Hz, 2H), 8.18–8.12 (m, 2H), 7.81–7.72 (m, 2H), 7.13 (dd, J = 2.8 Hz, 12 Hz, 1H), 7.06–7.02 (m, 1H), 6.94 (dd, J = 4 Hz, 13.2 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ = 158.3, 155.9, 152.7, 151.52, 143.3, 141.5, 139.4, 135.6, 130.3, 130.2, 129.6, 129.5, 129.1, 127.2; anal. calcd for C₂₀H₁₂ClFN₂: C, 71.75; H, 3.61; N, 8.37; found: C, 71.14, H, 3.48, N, 8.32.

2-(3′-(Methylsulfonyl)biphenyl-4-yl)quinoxaline (4u). Pale yellow solid; yield 95%; (Rf = 0.48 in hexanes/EtOAc 95 : 05 v/v); MP 137–139 °C; IR (KBr): 3062, 2886, 1530, 1488, 1414, 1317, 1112, 1060 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.39 (s, 1H), 8.34 (d, J = 8.8 Hz, 2H), 8.24 (t, J = 4 Hz, 1H), 8.21–8.14 (m, 2H), 7.99–7.95 (m, 2H), 7.83 (d, J = 8 Hz, 2H), 7.81–7.78 (m, 2H), 7.71 (t, J = 12 Hz, 1H), 7.48–7.40 (m, 2H), 3.14 (s, 3H); ¹³C NMR (CDCl₃, 100 MHz): δ = 156.9, 151.0, 143.0, 142.3, 141.7, 140.6, 136.6, 132.2, 130.7, 129.0, 128.2, 127.9, 126.4, 125.8, 121.1, 44.5; anal. calcd for C₂₁H₁₆N₂O₂S: C, 69.98; H, 4.47; N, 7.77; found: C, 68.92, H, 4.40, N, 7.28.

4′-(Quinoxalin-2-yl)-[1,1′-biphenyl]-3-carbonitrile (4v). White solid; yield 90%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 129–131 °C; IR (KBr): 3056, 2228, 1531, 1482, 1417, 1319, 1052 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz); δ = 9.57 (s, 1H), 9.37 (s, 1H), 9.21 (s, 1H), 8.50 (s, 1H), 8.32 (d, J = 8.4 Hz, 2H), 8.18–8.12 (m, 2H), 7.79 (d, J = 8.4 Hz, 2H); ¹³C NMR (CDCl₃, 100 MHz): δ = 164.6, 162.2, 150.9, 145.9, 145.9, 145.84, 142.3, 141.6, 139.7, 139.6, 138.3, 136.5, 134.0, 130.4, 129.6, 128.2, 115.6, 109.8, 109.4; anal. calcd for C₂₁H₁₃N₂: C, 77.91; H, 3.92; N, 18.17; found: C, 76.88, H, 3.94, N, 18.12.

2-(4-(Pyridin-4-yl)phenyl)quinoxaline (4w). White solid; yield 91%; (Rf = 0.44 in hexanes/EtOAc 95 : 05 v/v); MP 138–140 °C; IR (KBr): 3056, 1529, 1486, 1418, 1315, 1062 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.39 (s, 1H), 8.7 (d, J = 7.2 Hz, 1H), 8.51 (d, J = 2.4 Hz, 1H), 8.36 (dt, J = 2 Hz, 8.8 Hz, 2H), 8.20–8.14 (m, 2H), 7.83 (dd, J = 1.6 Hz, 8.4 Hz, 1H), 7.82–7.76 (m, 4H), 7.68 (dt, J = 2.8 Hz, 12 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz): δ = 150.8, 144.0, 143.0, 142.32, 141.7, 138.0, 137.0, 130.4, 129.6, 129.1, 128.3, 127.9, 121.1, 120.9; anal. calcd for C₁₉H₁₃N₃: C, 80.54; H, 4.62; N, 14.83; found: C, 80.48, H, 4.06, N, 14.44.

2-(4-(5-Fluoropyridin-3-yl)phenyl)quinoxaline (4x). White solid; yield 90%; (Rf = 0.46 in hexanes/EtOAc 95 : 05 v/v); MP 139–141 °C; IR (KBr): 3056, 1528, 1489, 1413, 1316, 1048, 694 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.38 (s, 1H), 8.52 (d, J = 2 Hz, 1H), 8.34 (d, J = 8.4 Hz, 2H), 8.20–8.13 (m, 2H), 8.09–8.05 (m, 1H), 7.84–7.78 (m, 2H), 7.76 (d, J = 8.4 Hz, 2H), 7.07 (dd, J = 3.2 Hz, 12 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz); δ = 150.9, 145.9, 145.8, 143.0, 141.6, 139.3, 136.5, 134.0, 130.5, 129.6, 129.1, 128.1, 128.2, 127.7, 109.8, 109.5; anal. calcd for C₁₉H₁₂FN₃: C, 75.74; H, 4.01; N, 13.95; found: C, 75.24, H, 3.94, N, 13.68.

2-(4-(6-Fluoropyridin-3-yl)phenyl)quinoxaline (4y). White solid; yield 90%; (Rf = 0.44 in hexanes/EtOAc 95 : 05 v/v); MP 143–146 °C; IR (KBr): 3048, 1532, 1482, 1428, 1323, 1052, 702 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.35 (s, 1H), 8.54 (d, J = 8 Hz, 2H), 8.41 (s, 1H), 8.31–8.24 (m, 2H), 8.20–8.12 (m, 1H), 7.88–7.7 (m, 2H), 7.74 (d, J = 8.8 Hz, 2H), 7.16 (dd, J₁ = 12.4 Hz, J₂ = 3.2 Hz, 1H); ¹³C NMR (CDCl₃, 100 MHz); δ = 164.3, 153.5, 147.1, 145.8, 143.0, 142.8, 141.7, 138.50, 136.5, 134.0, 130.5, 129.8, 129.6, 129.1, 128.2, 127.7, 109.8, 109.3; anal. calcd for C₁₉H₁₂FN₃: C, 75.74, H, 4.01, N, 13.95; found: C, 75.44, H, 3.96, N, 13.56.

2,3-Bis(4-methoxyphenyl)quinoxaline (5b). White solid; yield 96%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 146–148 °C; (Lit: 147–148);^18a IR (KBr): 3008, 2964, 2842, 1604, 1508, 1460, 1392, 1346, 1286, 1240, 1172, 1024, 828, 764 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.14–7.91 (m, 2H), 7.6–7.37 (m, 3H), 7.34 (d, J = 8.4 Hz, 4H), 7.33 (d, J = 7.2 Hz, 4H), 3.82 (s, 6H); LCMS (ESI) [M + H]⁺ calculated C₂₂H₁₈N₂O₂ 343.14 found 343.20.

2-Methyl-3-phenylquinoxaline (5d). White solid; yield 92%; (Rf = 0.44 in hexanes/EtOAc 95 : 05 v/v); MP 54–56 °C; (Lit: 54–55);^18b IR (KBr): 3122, 1510, 1461, 1318, 1054, 719 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.25–8.11 (m, 2H), 7.73–7.17 (m, 4H), 7.5–7.51 (m, 3H), 2.73 (s, 3H); LCMS (ESI) [M + H]⁺ calculated C₁₅H₁₂N₂ 221.10 found 221.17.

Quinoxaline (5e). White solid; yield 90%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 30–32 °C; (Lit: 32–33);^18c IR (KBr); 1498, 1364, 1202, 1128, 1028, 956 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.82 (s, 2H), 8.12 (d, J = 8 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H); LCMS (ESI) [M + H]⁺ calculated C₈H₆N₂ 131.05 found 131.10.

2-(4-Chlorophenyl)-3-phenylquinoxaline (5f). White solid; yield 94%; (Rf = 0.40 in hexanes/EtOAc 95 : 05 v/v); MP 135–137 °C; (Lit: 136–138);^18a IR (KBr): 3058, 2926, 1724, 1588, 1490, 1472, 1440, 1398, 1342, 1087, 1056, 1012, 966, 848, 806, 760, 696 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.20–8.13 (m, 2H), 8.09–8.07 (m, 2H), 8.05–7.82 (m, 4H), 7.80–7.78 (m, 3H), 7.75 (d, J = 8.4 Hz, 2H); LCMS (ESI) [M + H]⁺ calculated C₂₀H₁₃Cl₂N₂ 317.08 found 317.14.

2,3-Bis(4-methoxyphenyl)-6,7-dimethylquinoxaline (5h). Yellow solid; yield 95%; (Rf = 0.42 in hexanes/EtOAc 95 : 05 v/v); MP 122–124 °C; (Lit: 123–125);^18a IR (KBr): 2930, 2833, 1603, 1508, 1455, 1417, 1340, 1298, 1172, 1023, 965, 828 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ = 7.82 (s, 2H), 7.60 (d, J = 8.4 Hz, 4H), 7.10 (d, J = 7.6 Hz, 4H), 3.92 (s, 6H), 2.42 (s, 6H); LCMS (ESI) [M + H]⁺ calculated C₂₄H₂₂Cl₂N₂O₂ 371.17 found 371.23.

6-Bromo-2,3-di(furan-2-yl)quinoxaline (5k). White solid; yield 96%; (Rf = 0.54 in hexanes/EtOAc 95 : 05 v/v); MP 132–134 °C; (Lit: 131–133);^18k IR (KBr): 3359, 1541, 1428, 1071, 835, 756 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.36 (d, J = 1.6 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.86 (dd, J = 2.4 Hz, 2.4 Hz, 1H), 7.68 (t, J = 1.6 Hz, 2H), 6.76–6.75 (m, 2H), 6.63–6.61 (m, 2H); LCMS (ESI) [M + H]⁺ calculated C₁₆H₉BrN₂O₂ 341.98 found 341.06.

6-Chloro-7-fluoro-2,3-diphenylquinoxaline (5m). White solid; yield 94%; (Rf = 0.58 in hexanes/EtOAc 95 : 05 v/v); MP 158–160 °C; (Lit: 150–152);^18f IR (KBr): 3418, 1466, 1344, 1216, 702 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 8.24 (d, J = 8.4 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.80–7.28 (m, 4H), 7.14–7.01 (m, 6H); LCMS (ESI) [M + H]⁺ calculated C₂₀H₁₂Cl₂N₂FCl 335.07 found 335.14.

6-Nitro-2,3-diphenylquinoxaline (5n). Yellow solid; yield 95%; (Rf = 0.52 in hexanes/EtOAc 95 : 05 v/v); MP 183–185 °C; (Lit: 184–186);^18a IR (KBr): 3080, 3057, 1612, 1518, 1398, 1340, 1054, 1023, 810, 767, 698 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 9.08 (d, J = 2.4 Hz, 1H), 8.54 (dd, J = 11.6 Hz, 2.4 Hz, 1H), 8.30 (d, J = 9.2 Hz, 1H), 7.58–7.54 (m, 4H), 7.43–7.36 (m, 6H); LCMS (ESI) [M + H]⁺ calculated C₂₀H₁₃Cl₂N₃O₂ 328.10 found 328.17.

2,3-Diphenyl-4a,5,6,7,8,8a-hexahydroquinoxaline (5p). White solid; yield 90%; (Rf = 0.48 in hexanes/EtOAc 95 : 05 v/v); MP 171–176 °C; (Lit: 170–172);^18d IR (KBr): 3048, 2936, 1612 cm⁻¹; ¹H NMR (CDCl₃, 400 MHz): δ = 7.55–7.49 (m, 4H), 7.28–7.20 (m, 6H), 2.84 (t, J = 9.2 Hz, 2H), 2.50 (d, J = 13.6 Hz, 2H), 1.89 (d, J = 9.2 Hz, 2H), 1.64–1.62 (m, 2H), 1.47–1.39 (m, 2H); LCMS (ESI) [M + H]⁺ calculated C₂₀H₂₀N₂ 289.16 found 289.22.

Note added after first publication

This article replaces the version first published on 26th February 2016, which contained errors in the characterisation data. The original HRMS data has been removed and replaced with LCMS data and elemental analysis for all new compounds reported. Previously known compounds have been referenced to the literature and LCMS data has been added. A new compound 4y has been added and the crystal structure determined as shown in Fig. 2.

Acknowledgements

KSR thanks to DST Indo-Korea (grant no. INT/Korea/dated 13.09.2011 and KBH thanks to UGC for providng UGC-BSR fellowship. We are also thankful to the Institute of Excellence (IOE) for providing NMR and XRD facility at the University of Mysore, Manasagangotri, Mysuru-570006, India, for the spectral data.

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Footnote

† Electronic supplementary information (ESI) available. ¹H and ¹³C NMR data and single crystal X-ray data for compound 4y. CCDC 1480288. For ESI and crystallographic data in CIF or other electronic format. See DOI: 10.1039/c6ra03078e

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