An eco-friendly Pictet–Spengler approach to pyrrolo- and indolo[1,2-a]quinoxalines using p-dodecylbenzenesulfonic acid as an efficient Brønsted acid catalyst

Abstract

A facile and environmentally benign Pictet–Spengler strategy for the synthesis of a series of biologically important pyrrolo- and indolo[1,2-a]quinoxalines has been developed by reacting 1-(2-aminophenyl)-pyrrole or 1-(2-aminophenyl)indoles with a wide range of aromatic aldehydes, acetophenones or isatins in ethanol at ambient temperature using p-dodecylbenzenesulfonic acid (p-DBSA) as an efficient Brønsted acid–surfactant combined catalyst. This methodology was found to be applicable to generate diverse quinoxaline derivatives in fairly good yields under mild reaction conditions.

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Introduction

Practising green chemistry concepts for the development of efficient, safe and sustainable synthetic procedures has been significantly recognised globally in recent years.¹ The use of hazardous solvents and reagents in chemical manufacture is one of the major factors that contributes towards environmental pollution. Therefore, significant attention has been focused on the search for environmentally benign alternatives to these toxic solvents and consequently, the design of greener methodology for the construction of various structurally diverse molecules in a one-pot operation.²

Quinoxaline derivatives are an important class of biologically active nitrogen heterocycles which exhibit a wide range of pharmacological profiles.³ In particular, pyrrolo[1,2-a]quinoxalines substituted at the C-4 position have shown diverse biological activities such as anti-cancer,⁴ anti-malarial,⁵ and anti-proliferative⁶ activities. Furthermore, these molecules are reported as inhibitors of human protein kinase CK2,⁷ glucagon receptor antagonist⁸ and 5HT₃ receptor agonist.⁹ In addition, these compounds were also found to be applicable in the synthesis of GABA benzodiazepine receptor agonists or antagonists.¹⁰ Similarly, indolo[1,2-a]quinoxaline analogues have demonstrated interesting anti-fungal activities.¹¹ Due to the wide range of applications, a significant number of synthetic protocols¹² have been devised in the past for the preparation of various 4,5-dihydropyrrolo[1,2-a]quinoxalines,¹³ pyrrolo[1,2-a]quinoxalines,¹⁴ indolo[1,2-a]quinoxalines¹⁵ and their spiro derivatives.¹⁶ Among these, the Pictet–Spengler reaction is the most extensively used approach for the construction of pyrrolo[1,2-a]quinoxaline heterocycles.¹⁷ According to this protocol, the reaction proceeds with the initial formation of a Schiff’s base intermediate after the elimination of a water molecule followed by intramolecular cyclization to give a dihydro derivative, which subsequently on oxidation affords pyrrolo[1,2-a]quinoxalines. Although these reported synthetic strategies are effective, they still suffer from a number of demerits such as long reaction times, harsh reaction conditions and use of hazardous organic solvents. Therefore, an efficient, economical, environmentally friendly and versatile methodology for the synthesis of diverse pyrrolo- and indolo[1,2-a]quinoxaline scaffolds is highly desired.

Over the years, surfactant combined catalysts have been employed as a substitute for toxic catalysts in various environmentally benign protocols.¹⁸ Among these, p-dodecylbenzenesulfonic acid (p-DBSA) has emerged as a cheap, commercially available, non-hygroscopic, non-volatile, air-stable and efficient Brønsted acid–surfactant combined catalyst for carrying out a variety of useful organic transformations.¹⁹ This intrinsic catalytic efficiency of p-DBSA prompted us to investigate its further ability to catalyze the Pictet–Spengler reaction for the construction of various pyrrolo[1,2-a]quinoxaline analogues.

In the course of our interest to develop eco-friendly synthetic methodologies for useful organic transformations,²⁰ we wish to report herein a convenient and greener practical protocol for the synthesis of a series of various 4-arylpyrrolo[1,2-a]quinoxalines, 6-arylindolo[1,2-a]quinoxalines, 4-aryl-4-methyl-4,5-dihydropyrrolo[1,2-a]quinoxalines, 5′H-spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-ones and 5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one derivatives through a Pictet–Spengler condensation cyclization reaction of 1-(2-aminophenyl)pyrrole or 1-(2-aminophenyl)indoles with aromatic aldehydes, acetophenones or isatins in ethanol using p-DBSA as an efficient Brønsted acid–surfactant combined catalyst under mild reaction conditions. The results are summarized in Tables 1–4.

Results and discussion

For a facile and eco-friendly access to a series of pyrrolo- and indolo[1,2-a]quinoxaline scaffolds, initially the reaction was performed at room temperature using 1-(2-aminophenyl)pyrrole and benzaldehyde as model substrates in the presence of a catalytic amount of DBSA in ethanol for 2 hours followed by oxidation in the presence of 1 equivalent of KMnO₄ and the desired product 3a was obtained as a white solid in 89% yield (Table 1, entry 1). It is interesting to note that the yield of the product 3a was found to be same even after decreasing the reaction time from 2 hours to 30 min (Table 1, entry 2). However, the yield of the reaction was significantly affected by varying the catalyst load. A significant decrease in the yield of compound 3a was observed on decreasing the catalyst load from 10 mol% to 5 mol% (Table 1, entry 3) whereas, increasing the amount of p-DBSA up to 20 mol% did not improve the yield of desired product significantly (Table 1, entries 1, 4 and 5).

Table 1 Optimization of the reaction conditions for the synthesis of 4-phenylpyrrolo[1,2-a]quinoxaline (3a)^a

Entry	Catalyst (mol%)	Solvent	Time^b (h)	Yield^c (%) 3a
a Reagents and conditions: (a) 1-(2-aminophenyl)pyrrole 1a (1.0 mmol), benzaldehyde 2a (1.2 mmol), solvent (2.0 mL), 25 °C; (b) KMnO4 (1.0 mmol), 15 min.b Total reaction time including KMnO4 treatment.c Isolated yields after column chromatography.
1	p-DBSA (10)	EtOH	2.0	89
2	p-DBSA (10)	EtOH	0.5	89
3	p-DBSA (5)	EtOH	0.5	38
4	p-DBSA (15)	EtOH	0.5	90
5	p-DBSA (20)	EtOH	0.5	92
6	p-DBSA (0)	EtOH	0.5	Trace
7	p-DBSA (10)	THF	0.5	53
8	p-DBSA (10)	CH3CN	0.5	38
9	p-DBSA (10)	^tBuOH	0.5	38
10	p-DBSA (10)	PPG	0.5	33
11	p-DBSA (10)	H2O	0.5	45
12	p-DBSA (10)	EtOH : H2O (1 : 1)	0.5	65
13	p-DBSA (10)	—	0.5	35
14	PTSA (10)	EtOH	0.5	68
15	CH3COOH (10)	EtOH	0.5	63
16	TFA (10)	EtOH	0.5	74

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In contrast, the reaction performed in the absence of catalyst under identical conditions afforded only a trace amount of desired product 3a (Table 1, entry 6), demonstrating the catalytic role of p-DBSA in the synthesis of 4-phenylpyrrolo[1,2-a]quinoxaline (3a). Therefore, 10 mol% p-DBSA was selected as the optimum catalyst load for performing further reactions.

We next examined the effect of other solvents on the rate of reaction and the results are summarized in Table 1. The best results were obtained when the reaction was carried out in ethanol as solvent medium (Table 1, entries 1, 2, 4 and 5) while the reaction proceeded sluggishly in solvents such as THF, ^tBuOH, CH₃CN, PPG and provided the product 3a in poor to moderate yields (Table 1, entries 7–10). In addition, when the reaction was performed in water as a solvent, a low yield (45%) of the product 3a was obtained possibly due to the heterogeneous mixture of the reacting substrates (Table 1, entry 11). To improve the solubility of the reacting substrates, the reaction was also carried out in 50% ethanol in water but the yield of desired product did not increase significantly (Table 1, entry 12). Furthermore, the formation of product 3a was also found to be sluggish under solvent free conditions and only 35% isolated yield was observed (Table 1, entry 13). Based on these observations, ethanol was chosen as the best solvent to carry out this organic transformation.

The catalytic efficiency of p-DBSA was also compared with other acidic catalysts such as PTSA, acetic acid and TFA and it was observed that p-DBSA is the best suited catalyst for this reaction (Table 1, entries 14–16). It is noteworthy to mention that the reaction in the absence of KMnO₄ at 25 °C affords only the intermediate, 4,5-dihydro-4-phenylpyrrolo[1,2-a]quinoxaline in 90% yield. Hence, the optimal conditions for the model reaction were found to be 10 mol% p-DBSA in ethanol followed by oxidation in the presence of 1 equivalent of KMnO₄ at 25 °C.

Under the optimized conditions, the scope and generality of this protocol were investigated by treating 1-(2-aminophenyl)pyrrole or 1-(2-aminophenyl)indoles with a variety of aromatic and heteroaromatic aldehydes at ambient temperature in ethanol containing 10 mol% p-DBSA followed by oxidation in the presence of 1 equivalent of KMnO₄ to afford a series of pyrrolo- and indolo[1,2-a]quinoxaline derivatives (3a–o) in moderate to good yields (Table 2). In general, the reaction of aromatic aldehydes bearing both electron-withdrawing and electron-donating substituents on the aromatic ring proceeded well with 1-(2-aminophenyl)pyrrole and afforded the corresponding products (3a–f, 3k and 3l) in good to excellent yields (Table 2, entries 1–6 and 11–12). In contrast, the reaction with heterocyclic aldehydes provided relatively lower yields of the products (3g–j) (Table 2, entries 7–10). On the other hand, the reaction of 1-(2-aminophenyl)indoles and aromatic aldehydes is found to be sluggish and provided the corresponding 6-arylindolo[1,2-a]quinoxaline products (3m–o) in moderate yields due to the lower nucleophilicity of the indole substituted anilines as compared to the 1-(2-aminophenyl)pyrrole²¹ (Table 2, entries 13–15).

Table 2 Synthesis of 4-arylpyrrolo[1,2-a]quinoxalines (3a–l), 6-arylindolo[1,2-a]quinoxalines (3m,n), 7-methyl-6-(pyridin-4-yl)indolo[1,2-a]quinoxaline (3o)^a

Entry	Amine	Aldehyde	Product	Yield^b (%)
a Reagents and conditions: (a) amines 1a–c (1.0 mmol), aldehydes 2a–m (1.2 mmol), p-DBSA (0.10 mmol), EtOH (2.0 mL); (b) KMnO4 (1.0 mmol).b Isolated yields after column chromatography.
1				89
2				90
3				88
4				88
5				75
6				75
7				40
8				62
9				77
10				80
11				75
12				82
13				52
14				40
15				52

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After chromatographic purification, the isolated products (3a–o) were fully characterized on the basis of detailed spectral analysis including IR, ¹H NMR, ¹³C NMR and high resolution mass. The IR spectrum of compound 3a showed a characteristic absorption peak at 1599 cm⁻¹ due to the stretching of the C=N bond. In the ¹H NMR spectrum of compound 3a, one of the three pyrrolic protons appeared as a multiplet between δ 7.79–8.06 ppm along with three phenyl protons whereas the other two pyrrolic protons were found as a doublet at δ 7.00 ppm (J = 4.39 Hz) and a multiplet between δ 6.88–6.90 ppm for one proton each, respectively. Besides these, two sets of the remaining phenyl protons were also observed as a doublet for one proton at δ 7.86 ppm (J = 8.05 Hz) and a multiplet for 5 protons between δ 7.44–7.57 ppm, respectively. Additionally, the ¹³C NMR spectrum showed characteristic peaks at 108.7, 114.0 and 114.6 ppm due to the carbons of the pyrrolic moiety whereas a peak at 154.4 ppm corresponds to the imine carbon of the quinoxaline ring. The structure of compound 3a was further supported by mass spectral analysis which showed a [M + H]⁺ ion peak at m/z 245.1067 for the molecular formula C₁₇H₁₃N₂.

Furthermore, the optimized methodology was extended to construct various 4-methyl-4-aryl-4,5-dihydropyrrolo[1,2-a]quinoxalines in one-pot by reacting 1-(2-aminophenyl)pyrrole (1a) with aromatic ketones in a 1 : 1.2 ratio in ethanol at room temperature using 10 mol% p-DBSA (Table 3).

Table 3 Synthesis of 4-methyl-4-aryl-4,5-dihydropyrrolo[1,2-a]quinoxalines (5a–d)^a

Entry	Ketone	Product	Yield^b (%)
a Reagents and conditions: amine 1a (1.0 mmol), ketones 4a–d (1.2 mmol), p-DBSA (0.10 mmol), EtOH (2.0 mL).b Isolated yields of products (5a–d) after column chromatography.
1			82
2			83
3			82
4			86

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To our delight, the desired products (5a–d) were obtained in good yields of 82–86% within 30 minutes. As expected, the reaction proceeded at a slightly slow rate in the case of less reactive aromatic ketones as compared to the aryl aldehydes and the desired products were obtained in a relatively longer reaction time. On studying the effect of substituents present in acetophenones on the rate of reaction, it has been observed that aromatic ketones having a halogen atom at the para position afford lower yields of the products with decreasing electronegativity (Table 3, entries 2 and 3). The best results were obtained when the reaction of 1a was carried out with 4-phenylacetophenone possibly due to the extended conjugation of the additional phenyl ring (Table 3, entry 4). The structures of compounds 5a–d were established on the basis of their spectral data. In the IR spectrum of compound 5a, a characteristic absorption peak due to NH stretching appeared at 3367 cm⁻¹. The ¹H NMR of the product 5a showed a characteristic broad singlet at δ 4.39 ppm due to the NH proton and a singlet at δ 1.90 ppm due to three methyl protons. The three pyrrolic protons appeared separately as a double doublet at δ 6.05 ppm (J₁ = 3.66 Hz and J₂ = 1.83 Hz), a triplet at δ 6.33 ppm (J = 3.05 Hz) and a multiplet between δ 7.14–7.18 ppm, respectively. In the ¹³C NMR spectrum, peaks at δ 29.2 and 56.8 ppm were assigned to the methyl carbon and quaternary carbon of the dihydroquinoxaline ring, respectively. The high resolution ESI-mass spectral analysis further confirmed the formation of compound 5a by showing the [M + H]⁺ ion peak at m/z 261.1386 for the molecular formula C₁₈H₁₇N₂.

After the successful synthesis of a series of pyrrolo[1,2-a]quinoxaline and dihydropyrrolo[1,2-a]quinoxaline derivatives in good yields, we turned our attention towards the synthesis of spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-one derivatives (7a–j) by reacting isatin derivatives either with 1-(2-aminophenyl)pyrrole or 2-(1H-indol-1-yl)anilines under optimized reaction conditions. We are delighted to report that the present eco-friendly Pictet–Spengler protocol has also been successfully extended to prepare a series of spiro derivatives in good to excellent yields (Table 4). As shown in the Table 4, this reaction proceeded satisfactorily with a variety of isatins containing both electron donating as well as electron withdrawing substituents and provided the target products in good to excellent yields (79–87%). The isolated desired products (7a–j) were characterized spectroscopically. The IR spectrum of compound 7a showed characteristic absorption bands at 3313, 3239 and 1721 cm⁻¹ due to the stretching of NH and C=O groups, respectively. The ¹H NMR of compound 7a showed two singlets at δ 8.32 and 4.30 ppm due to the presence of NH protons. Two multiplets between δ 7.21–7.50 ppm and δ 5.60–5.61 ppm appeared due to two of the pyrrolic protons whereas the remaining one pyrrolic proton appeared as a triplet at δ 6.24 ppm (J = 3.05 Hz). In addition, the ¹³C NMR spectrum of 7a showed a characteristic peak at δ 61.1 ppm which corresponds to the quaternary spiro-carbon of the dihydroquinoxaline ring. High resolution mass data of compound 7a also supported the assigned structure by showing the [M + H]⁺ ion peak at m/z 288.1131. Furthermore, the structure of compound (7d) was finally confirmed by single crystal X-ray analysis (Fig. 1).²²

Table 4 Synthesis of 5′H-spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-ones (7a–d), 5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-ones (7e–h) and 7′-methyl-5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-ones (7i,j)^a

Entry	Amine	Isatin	Product	Yield^b (%)
a Reagents and conditions: amines 1a–c (1.0 mmol), isatins 6a–d (1.2 mmol), p-DBSA (0.10 mmol), EtOH (2.0 mL).b Isolated yields after column chromatography.
1				83
2				84
3				80
4				80
5				82
6				79
7				80
8				83
9				87
10				79

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Fig. 1 X-ray crystal structure of compound 7d.

A possible mechanistic pathway for the synthesis of pyrrolo- and indolo[1,2-a]quinoxalines is shown in Fig. 2. It is likely that the reaction proceeds via the protonation of the corresponding carbonyl compounds (aldehydes/ketones/diketones) in the presence of p-DBSA as a Brønsted acid catalyst followed by a nucleophilic attack of pyrrole or indole substituted aniline to generate an electron deficient iminium ion (III or VII) which undergoes intramolecular cyclization and deprotonation to afford desired products 5a–d and 7a–j in good to moderate yields whereas in the case of aldehydes, the reaction initially provided a dihydro-pyrrolo-or indolo[1,2-a]quinoxaline intermediate which on oxidation in the presence of KMnO₄ afforded the desired products (3a–o) in 40–90% yields.

Fig. 2 Plausible reaction mechanism for the synthesis of pyrrolo- and indolo[1,2-a]quinoxalines.

Conclusions

In summary, we have developed an energy efficient, facile, environmentally friendly practical methodology for easy access to various pyrrolo[1,2-a]quinoxaline, dihydropyrrolo[1,2-a]quinoxaline and spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-one derivatives via Pictet–Spengler reaction using p-DBSA as an efficient Brønsted acid catalyst in ethanol at room temperature. The present synthetic protocol demonstrates many key advantages such as mild reaction conditions, short reaction times, good to excellent yields of the products and the use of non-hazardous solvent medium for the synthesis of these biologically active nitrogen heterocycles.

Experimental

General

All the chemicals were purchased from Sigma-Aldrich and used without further purification. The progress of the reaction was monitored by thin layer chromatography (TLC) using silica gel 60 F₂₅₄ (pre coated aluminium sheets) from Merck. TLC spots were visualised by UV-light followed by iodine. NMR spectra were obtained in CDCl₃ or DMSO-d₆ on a Jeol ECX 400 MHz NMR spectrometer using TMS as an internal standard and chemical shifts are expressed in parts per million (ppm) and coupling constants (J) are reported in Hertz (Hz). Infrared spectra were recorded on a Perkin Elmer IR spectrometer and absorption maxima (ν_max) are given in cm⁻¹. The melting points were determined in open capillary tubes on Buchi M-560 melting point apparatus and are uncorrected. Mass spectra (ESI-HRMS) were recorded on 6530 QTOF LCMS and microTOF-Q ll 10262 mass spectrometers. 2-(1H-Indol-1-yl)aniline and 2-(3-methylindol-1-yl)phenylamine (1b and 1c) were synthesized according to the literature procedure.²³

General procedure for the synthesis of 4-arylpyrrolo[1,2-a]quinoxalines (3a–l), 6-arylindolo[1,2-a]quinoxalines (3m,n), 7-methyl-6-(pyridin-4-yl)indolo[1,2-a]quinoxaline (3o)

To a well stirred solution of p-DBSA (0.1 mmol) in ethanol (2 mL), aromatic aldehyde (1.2 mmol) was added followed by the addition of 1-(2-aminophenyl)pyrrole or 2-(1H-indol-1-yl)aniline or 2-(3-methylindol-1-yl)phenylamine (100 mg, 1.0 mmol). The reaction mixture was stirred at 25 °C for 15 minutes. After complete consumption of the starting materials as evident by TLC, the mixture was treated with KMnO₄ (1.0 mmol) and stirred for an additional 15 min at 25 °C. The excess of solvent was then evaporated and the residue thus obtained was treated with saturated NaHCO₃ solution (20 mL). The product was then extracted with ethyl acetate (10 mL × 3 times). The organic layers were combined, washed with water (20 mL × 3 times) and brine solution (20 mL). Finally, the organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure to dryness. The crude product was purified by column chromatography over silica gel (60–120 mesh size) using 5–20% ethyl acetate in heptane as eluent to furnish the desired products (3a–o) in good yields. The characterization data of known compounds (3a and 3n) were found to be in good agreement with the reported data.^15b,24

4-(4-Nitrophenyl)pyrrolo[1,2-a]quinoxaline (3b). Yellow solid, yield: 163 mg (90%); mp 221–223 °C; IR (CHCl₃) ν_max: 2927, 1598, 1348, 1096, 852, 751, 727 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.41 (d, J = 8.79 Hz, 2H, ArH), 8.20 (d, J = 8.79 Hz, 2H, ArH), 8.04–8.08 (m, 2H, pyrrolic H and ArH), 7.93 (d, J = 8.05 Hz, 1H, ArH), 7.57–7.61 (m, 1H, ArH), 7.49–7.53 (m, 1H, ArH), 6.95–6.97 (m, 2H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 151.8, 148.5, 144.4, 135.8, 130.4, 129.6, 128.3, 127.1, 125.6, 124.7, 123.7, 115.1, 114.4, 113.7, 108.2; HRMS (ESI, m/z) calcd for C₁₇H₁₂N₃O₂: 290.0924 [M + H]⁺, found: 290.0924.

4-(Pyridin-4-yl)pyrrolo[1,2-a]quinoxaline (3c). Brown solid, yield: 136 mg (88%); mp 179–180 °C; IR (CHCl₃) ν_max: 2928, 1598, 1407, 1376, 1250, 1039, 824, 753, 729 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.82–8.83 (m, 2H, pyridyl H), 8.04–8.06 (m, 2H, pyridyl H), 7.90–7.93 (m, 3H, pyrrolic H and ArH), 7.58 (t, J = 7.32 Hz, 1H, ArH), 7.50 (t, J = 7.32 Hz, 1H, ArH), 6.93–7.00 (m, 2H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 151.3, 149.7, 146.0, 135.7, 130.3, 128.3, 127.1, 125.4, 124.5, 123.0, 115.0, 114.3, 113.6, 108.1; HRMS (ESI, m/z) calcd for C₁₆H₁₂N₃: 246.1026 [M + H]⁺, found: 246.1033.

2-(Pyridin-2-yl)pyrrolo[1,2-a]quinoxaline (3d). Green solid, yield: 136 mg (88%); mp 106–108 °C; IR (CHCl₃) ν_max: 3061, 2925, 1583, 1531, 1475, 1441, 1367, 1096, 1037, 812, 756, 743 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.81–8.82 (m, 1H, pyridyl H), 8.41 (d, J = 8.05 Hz, 1H, pyridyl H), 8.06 (d, J = 8.05 Hz, 1H, pyridyl H), 8.01 (s, 1H, pyridyl H), 7.90 (d, J = 8.05 Hz, 2H, ArH), 7.73 (d, J = 3.66 Hz, 1H, pyrrolic H), 7.40–7.56 (m, 3H, pyrrolic H and ArH), 6.95–6.97 (m, 1H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 156.3, 151.1, 148.8, 136.6, 135.6, 130.2, 127.9, 127.5, 125.0, 124.5, 124.2, 123.3, 114.39, 114.31, 113.6, 110.5; HRMS (ESI, m/z) calcd for C₁₆H₁₂N₃: 246.1025 [M + H]⁺, found: 246.1026.

4-(9H-Fluoren-3-yl)pyrrolo[1,2-a]quinoxaline (3e). Light brown solid, yield: 157 mg (75%); mp 170–172 °C; IR (CHCl₃) ν_max: 3067, 2925, 1613, 1519, 1477, 1367, 1320, 1216, 1098, 837, 797, 753, 718 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.20 (s, 1H, ArH), 8.04–8.08 (m, 2H, ArH), 8.00–8.01 (m, 1H, pyrrolic H), 7.94 (d, J = 8.05 Hz, 1H, ArH), 7.86–7.90 (m, 2H, ArH), 7.60 (d, J = 7.32 Hz, 1H, ArH), 7.47–7.54 (m, 2H, ArH), 7.43 (t, J = 7.32 Hz, 1H, ArH), 7.36 (t, J = 7.32 Hz, 1H, ArH), 7.06–7.07 (m, 1H, pyrrolic H), 6.90–6.92 (m, 1H, pyrrolic H), 4.02 (s, 2H, CH₂); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 154.4, 143.8, 143.5, 143.2, 141.0, 136.8, 136.2, 130.0, 127.4, 127.2, 127.1, 127.0, 126.7, 125.3, 125.1, 125.0, 120.2, 119.7, 114.5, 113.8, 113.5, 108.7, 36.9; HRMS (ESI, m/z) calcd for C₂₄H₁₇N₂: 333.1386 [M + H]⁺, found: 333.1387.

4-(Pyren-2-yl)pyrrolo[1,2-a]quinoxaline (3f). Light brown solid, yield: 174 mg (75%); mp 218–220 °C; IR (CHCl₃) ν_max: 3041, 1596, 1474, 1418, 1374, 1093, 1036, 847, 754, 716 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.31 (s, 2H, ArH), 8.23–8.27 (m, 2H, ArH), 8.14–8.19 (m, 4H, ArH), 7.97–8.06 (m, 4H, pyrrolic H and ArH), 7.51–7.63 (m, 2H, ArH), 6.83–6.85 (m, 1H, pyrrolic H), 6.54–6.55 (m, 1H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 155.0, 136.2, 132.5, 131.9, 131.2, 130.8, 130.3, 129.3, 128.1, 127.8, 127.7, 127.3, 127.1, 126.8, 126.0, 125.4, 125.38, 125.32, 125.0, 124.6, 124.5, 114.5, 114.1, 113.7, 109.2; HRMS (ESI, m/z) calcd for C₂₇H₁₇N₂: 369.1386 [M + H]⁺, found: 369.1387.

4-(1H-Indol-3-yl)pyrrolo[1,2-a]quinoxaline (3g). Light brown solid, yield: 72 mg (40%); mp 118–120 °C; IR (CHCl₃) ν_max: 3412, 2923, 1644, 1447, 1337, 1239, 1025, 998, 751 cm⁻¹; ¹H NMR (400 MHz, CDCl₃ + DMSO-d₆): δ(ppm) 10.80 (s, 1H, NH), 7.94–7.95 (m, 1H, pyrrolic H), 7.48–7.50 (m, 2H, ArH), 7.30–7.37 (m, 2H, ArH), 6.78–6.85 (m, 3H, ArH), 6.53–6.57 (m, 3H, pyrrolic H and ArH), 6.23 (s, 1H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃ + DMSO-d₆): δ (ppm) 149.2, 136.0, 135.4, 128.4, 126.5, 125.7, 125.67, 125.64, 124.27, 124.20, 121.6, 121.3, 119.8, 113.6, 112.9, 112.8, 111.0, 106.8 ppm; HRMS (ESI, m/z) calcd for C₁₉H₁₄N₃: 284.1182 [M + H]⁺, found: 284.1189.

4-(Furan-2-yl)pyrrolo[1,2-a]quinoxaline (3h). Brown solid, yield: 92 mg (62%); mp 99–101 °C; IR (CHCl₃) ν_max: 3140, 2922, 2851, 1589, 1475, 1364, 1046, 1006, 882, 751 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.98–8.02 (m, 2H, ArH), 7.85 (d, J = 7.32 Hz, 1H, ArH), 7.71 (s, 1H, ArH), 7.40–7.50 (m, 4H, pyrrolic H and furyl H), 6.93 (t, J = 3.36 Hz, 1H, pyrrolic H), 6.64 (br, 1H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ(ppm) 151.9, 144.2, 143.1, 135.4, 129.6, 127.0, 126.7, 125.0, 122.8, 114.2, 113.8, 113.3, 112.6, 111.8, 108.1; HRMS (ESI, m/z) calcd for C₁₅H₁₁N₂O: 235.0866 [M + H]⁺, found: 235.0872.

4-(1H-Pyrrol-2-yl)pyrrolo[1,2-a]quinoxaline (3i). Brown solid, yield: 114 mg (77%); mp 110–111 °C; IR (CHCl₃) ν_max: 3434, 3064, 1601, 1475, 1415, 1370, 1167, 1072, 1031, 932, 752, 688 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 10.20 (brs, 1H, NH), 7.92–7.97 (m, 2H, ArH), 7.84 (d, J = 8.54 Hz, 1H, ArH), 7.39–7.47 (m, 2H, pyrrolic H), 7.31 (d, J = 3.66 Hz, 1H, pyrrolic H), 7.18 (d, J = 3.05 Hz, 1H, pyrrolic H), 7.08 (s, 1H, ArH), 6.92–6.93 (m, 1H, pyrrolic H), 6.42 (t, J = 3.05 Hz, 1H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 145.7, 144.1, 135.0, 128.4, 126.7, 126.5, 125.2, 123.1, 121.6, 114.6, 114.0, 113.5, 112.4, 110.6, 107.9; HRMS (ESI, m/z) calcd for C₁₅H₁₂N₃: 234.1026 [M + H]⁺, found: 234.1035.

4-(Thiophen-2-yl)pyrrolo[1,2-a]quinoxaline (3j). Yellow solid, yield: 126 mg (80%); mp 116–117 °C; IR (CHCl₃) ν_max: 3064, 1583, 1524, 1442, 1433, 1365, 1218, 1101, 1067, 852, 754, cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.96–8.01 (m, 3H, ArH), 7.85 (dd, J₁ = 8.05 Hz, J₂ = 1.46 Hz, 1H, ArH), 7.55 (dd, J₁ = 5.13 Hz, J₂ = 1.46 Hz, 1H, thienyl H), 7.42–7.52 (m, 2H, pyrrolic H), 7.28 (dd, J₁ = 4.39 Hz, J₂ = 1.46 Hz, 1H, thienyl H), 7.22 (dd, J₁ = 5.13 Hz, J₂ = 3.66 Hz, 1H, thienyl H), 6.93 (t, J = 3.29 Hz, 1H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 147.2, 142.3, 135.6, 129.8, 128.6, 128.0, 127.7, 127.3, 126.8, 125.2, 123.9, 114.6, 113.9, 113.4, 107.7; HRMS (ESI, m/z) calcd for C₁₅H₁₁N₂S: 251.0637 [M + H]⁺, found: 251.0638.

4-(4-Methoxyphenyl)pyrrolo[1,2-a]quinoxaline (3k). White solid, yield: 130 mg (75%); mp 114–116 °C; IR (CHCl₃) ν_max: 2924, 2851, 1606, 1508, 1475, 1368, 1250, 1177, 1031, 834, 755, 715 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.98–8.03 (m, 4H, pyrrolic H and ArH), 7.87–7.88 (m, 1H, ArH), 7.45–7.50 (m, 2H, ArH), 7.05–7.07 (m, 2H, ArH), 7.00–7.01 (m, 1H, pyrrolic H), 6.88–6.90 (m, 1H, pyrrolic H), 3.90 (s, 3H, OCH₃); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 160.9, 153.8, 136.2, 130.9, 130.0, 129.9, 127.1, 126.9, 125.2, 125.1, 114.4, 113.89, 113.83, 113.5, 108.5, 55.3; HRMS (ESI, m/z) calcd for C₁₈H₁₅N₂O: 275.1179 [M + H]⁺, found: 275.1179.

4-(4-(Trifluoromethyl)phenyl)pyrrolo[1,2-a]quinoxaline (3l). Brown solid, yield: 161 mg (82%); mp 238–240 °C; IR (CHCl₃) ν_max: 2926, 1609, 1404, 1319, 1095, 1036, 758 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.13 (d, J = 7.79 Hz, 2H, ArH), 8.04–8.07 (m, 2H, pyrrolic H and ArH), 7.92 (dd, J₁ = 8.24 Hz, J₂ = 1.37 Hz, 1H, ArH), 7.81 (d, J = 8.24 Hz, 2H, ArH), 7.55–7.59 (m, 1H, ArH), 7.47–7.51 (m, 1H, ArH), 6.93–6.98 (m, 2H, pyrrolic H); ¹³C NMR (100 MHz, CDCl₃ + DMSO-d₆): δ (ppm) 149.7, 136.4 (d, ²J_C–F = 6.71 Hz), 131.5, 129.9, 128.6, 128.2, 125.4 (d, ³J_C–F = 5.75 Hz), 125.3, 124.7 (d, ⁴J_C–F = 3.83 Hz), 122.7, 122.6 (d, ¹J_C–F = 280.83 Hz), 119.0, 115.8, 113.9, 112.6; HRMS (ESI, m/z) calcd for C₁₈H₁₂F₃N₂: 313.0947 [M + H]⁺, found: 313.0952.

6-(4-Fluorophenyl)indolo[1,2-a]quinoxaline (3m). Yellow solid, yield: 77 mg (52%); mp 189–191 °C; IR (CHCl₃) ν_max: 2918, 2850, 1617, 1506, 1453, 1330, 1227, 742 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.53–8.58 (m, 2H, ArH), 8.07–8.12 (m, 3H, ArH), 7.98 (d, J = 7.93 Hz, 1H, ArH), 7.67 (t, J = 7.32 Hz, 1H, ArH), 7.61 (t, J = 7.32 Hz, 1H, ArH), 7.48–7.52 (m, 2H, ArH), 7.30–7.34 (m, 3H, pyrrolic H and ArH); ¹³C NMR (100 MHz, CDCl₃): δ(ppm) 163.8 (d, ¹J_C–F = 253.04 Hz), 155.0, 136.1, 134.3 (d, ⁴J_C–F = 2.88 Hz), 133.0, 130.6, 130.5, 130.4, 130.1, 129.1, 128.9, 128.4, 124.3 (d, ²J_C–F = 22.04 Hz), 122.7 (d, ³J_C–F = 4.79 Hz), 115.7, 115.5, 114.6, 114.5, 102.3; HRMS (ESI, m/z) calcd for C₂₁H₁₄FN₂: 313.1136 [M + H]⁺, found: 313.1141.

7-Methyl-6-(pyridin-4-yl)indolo[1,2-a]quinoxaline (3o). Orange solid, yield: 72 mg (52%); mp 235–237 °C; IR (CHCl₃) ν_max: 2922, 1597, 1451, 1399, 1211, 831, 745 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.84 (s, 2H, pyridyl H), 8.50 (t, J = 7.93 Hz, 2H, pyridyl H), 7.98–8.00 (m, 1H, ArH), 7.92 (d, J = 7.93 Hz, 1H, ArH), 7.60–7.65 (m, 4H, ArH), 7.40–7.50 (m, 2H, ArH), 2.11 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): δ (ppm) 154.7, 149.9, 147.3, 135.2, 132.0, 130.5, 130.3, 130.1, 129.0, 125.1, 124.7, 124.0, 123.4, 122.3, 120.8, 114.49, 114.40, 110.5, 11.3; HRMS (ESI, m/z) calcd for C₂₁H₁₆N₃: 310.1339 [M + H]⁺, found: 310.1345.

General procedure for the synthesis of 4-methyl-4-aryl-4,5-dihydropyrrolo[1,2-a]quinoxalines (5a–d)

To a well stirred solution of p-DBSA (0.1 mmol) in ethanol (2 mL), aromatic ketone (1.2 mmol) and 1-(2-aminophenyl)pyrrole (1.0 mmol) were added successively at 25 °C. The reaction mixture was stirred at the same temperature for 30 minutes. After completion of the reaction, the solvent was evaporated and the residue obtained was treated with saturated NaHCO₃ solution (5 mL). Then saturated brine solution (5 mL) was added. The product was extracted with ethyl acetate (10 mL × 3 times). The organic layers were combined, washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure to dryness. The crude product was purified by column chromatography over silica gel (60–120 mesh size) using 5–20% ethyl acetate in heptane as eluent to furnish the desired product in good yields. The spectral data of known compound (5a) are found to be in good agreement with the reported data.^13a

4-(4-Bromophenyl)-4-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (5b). White solid, yield: 178 mg (83%); mp 165–166 °C; IR (CHCl₃) ν_max: 3349, 2980, 1613, 1517, 1482, 1334, 1187, 1077, 778, 746 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.33–7.35 (m, 2H, ArH), 7.24–7.26 (m, 1H, ArH), 7.14–7.17 (m, 3H, pyrrolic H and ArH), 6.92–6.96 (m, 1H, ArH), 6.75–6.82 (m, 2H, ArH), 6.33 (t, J = 3.21 Hz, 1H, pyrrolic H), 6.05 (dd, J₁ = 3.21 Hz, J₂ = 1.37 Hz, 1H, pyrrolic H), 4.33 (s, 1H, NH), 1.87 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): 145.4, 134.7, 132.3, 131.2, 127.5, 125.6, 124.7, 120.8, 119.5, 115.8, 114.6, 114.4, 110.0, 104.5, 56.5, 29.0; HRMS (ESI, m/z) calcd for C₁₈H₁₆BrN₂: 339.0491 [M + H]⁺, found: 339.0490.

4-(4-Iodophenyl)-4-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (5c). White solid, yield: 200 mg (82%); mp 153–154 °C; IR (CHCl₃) ν_max: 3353, 2978, 2930, 1610, 1597, 1515, 1482, 1332, 1187, 1073, 746 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.53–7.55 (m, 2H, ArH), 7.24–7.26 (m, 1H, ArH), 7.15–7.16 (m, 1H, pyrrolic H), 7.01–7.03 (m, 2H, ArH), 6.92–6.96 (m, 1H, ArH), 6.75–6.81 (m, 2H, ArH), 6.33 (t, J = 3.05 Hz, 1H, pyrrolic H), 6.04–6.05 (m, 1H, pyrrolic H), 4.33 (s, 1H, NH), 1.86 (s, 3H, CH₃);¹³C NMR (100 MHz, CDCl₃): 146.2, 137.3, 134.8, 132.3, 127.9, 125.7, 124.8, 119.6, 115.9, 114.7, 114.5, 110.1, 104.6, 92.7, 56.7 29.1; HRMS (ESI, m/z) calcd for C₁₈H₁₆IN₂: 387.0353 [M + H]⁺, found: 387.0351.

4-([1,1′-Biphenyl]-4-yl)-4-methyl-4,5-dihydropyrrolo[1,2-a]quinoxaline (5d). White solid, yield: 182 mg (86%); mp 158–159 °C; IR (CHCl₃) ν_max: 3373, 3029, 2985, 2927, 1612, 1515, 1417, 1334, 1189, 1074, 839, 746, 698 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.47 (d, J = 7.93 Hz, 2H, ArH), 7.42 (d, J = 7.93 Hz, 2H, ArH), 7.33–7.36 (m, 4H, ArH), 7.29–7.31 (m, 1H, ArH), 7.23–7.27 (m, 1H, ArH), 7.17–7.18 (m, 1H, pyrrolic H), 6.91–6.94 (m, 1H, ArH), 6.75–6.80 (m, 2H, ArH), 6.32–6.33 (m, 1H, pyrrolic H), 6.04–6.07 (m, 1H, pyrrolic H), 4.37 (s, 1H, NH), 1.90 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): 145.3, 140.5, 139.6, 135.0, 132.8, 128.6, 127.1, 126.95, 126.90, 126.1, 125.6, 124.7, 119.2, 115.7, 114.6, 114.2, 109.9, 104.5, 56.7, 29.2; HRMS (ESI, m/z) calcd for C₂₄H₂₁N₂: 337.1699 [M + H]⁺, found: 337.1708.

General procedure for the synthesis of 5′H-spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-ones (7a–d) and 5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-ones (7e–j)

To a well stirred solution of p-DBSA (0.1 mmol) in ethanol (2 mL), isatin derivative (1.2 mmol), and 1-(2-aminophenyl)pyrrole or 2-(1H-indol-1-yl)aniline or 2-(3-methylindol-1-yl)phenylamine (1.0 mmol) were added at 25 °C. The reaction mixture was stirred at same temperature for the 30 minutes. After complete consumption of the starting materials as shown by TLC, the reaction mixture was then evaporated and the residue thus obtained was treated with saturated NaHCO₃ solution (5 mL) followed by the addition of saturated brine solution (5 mL). The product was extracted with ethyl acetate (10 mL × 3 times). The organic layers were combined, washed with water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude product was purified by column chromatography over silica gel (60–120 mesh size) using 5–20% ethyl acetate in heptane as eluent to furnish the desired product in good yields. The characterization data of known compound (7a) are matched with the reported data.¹⁶

5-Chloro-5′H-spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-one (7b). Orange solid, yield: 170 mg (84%); mp 116–118 °C; IR (CHCl₃) ν_max: 3322, 3247, 2926, 2854, 1720, 1617, 1477, 1333, 1196, 822, 753 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.12 (s, 1H, NH), 7.23–7.38 (m, 4H, pyrrolic H and ArH), 6.88–6.98 (m, 2H, ArH), 6.63–6.73 (m, 2H, ArH), 6.26 (t, J = 3.05 Hz, 1H, pyrrolic H), 5.61–5.62 (m, 1H, pyrrolic H), 4.32 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl₃): 178.1, 139.7, 133.8, 131.9, 130.1, 128.4, 126.1, 124.9, 124.8, 124.3, 119.5, 116.0, 115.4, 114.2, 111.8, 110.5, 106.2, 61.4; HRMS (ESI, m/z) calcd for C₁₈H₁₃ClN₃O: 322.0742 [M + H]⁺, found: 322.0738.

5-Methyl-5′H-spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-one (7c). Orange solid, yield: 152 mg (80%); mp 130–132 °C; IR (CHCl₃) ν_max: 3328, 3246, 2924, 1718, 1624, 1508, 1497, 1333, 1301, 1207, 1156, 764 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.04 (s, 1H, NH), 7.36 (d, J = 7.32 Hz, 1H, ArH), 7.20–7.28 (m, 2H, ArH), 7.06 (d, J = 7.93 Hz, 1H, ArH), 6.96 (t, J = 7.32 Hz, 1H, ArH), 6.87 (t, J = 7.32 Hz, 1H, ArH), 6.66–6.69 (m, 2H, ArH and pyrrolic H), 6.25 (t, J = 3.05 Hz, 1H, pyrrolic H), 5.62 (d, J = 2.44 Hz, 1H, pyrrolic H), 4.29 (s, 1H, NH), 2.30 (s, 3H, CH₃); HRMS (ESI, m/z) calcd for C₁₉H₁₅N₃NaO: 324.1107 [M + Na]⁺, found: 324.1114.

1-Methyl-5′H-spiro[indoline-3,4′-pyrrolo[1,2-a]quinoxalin]-2-one (7d). Pale white solid, yield: 152 mg (80%); mp 261–262 °C; IR (CHCl₃) ν_max: 3328, 2928, 1717, 1610, 1517, 1466, 1334, 1091, 737 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 7.37–7.45 (m, 3H, ArH), 7.28–7.29 (m, 1H, ArH), 7.13 (t, J = 7.63 Hz, 1H, ArH) 6.96–7.00 (m, 1H, ArH), 6.88–6.91 (m, 2H, ArH), 6.73–6.75 (m, 1H, pyrrolic H), 6.23 (t, J = 3.05 Hz, 1H, pyrrolic H), 5.56–5.57 (m, 1H, pyrrolic H), 4.22 (s, 1H, NH), 3.14 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃ + DMSO-d₆): 175.3, 143.8, 134.2, 130.0, 129.6, 125.4, 125.3, 125.0, 124.5, 123.1, 119.2, 115.6, 115.1, 114.0, 110.0, 108.1, 105.5, 60.5, 25.9; HRMS (ESI, m/z) calcd for C₁₉H₁₆N₃O: 302.1288 [M + H]⁺, found: 302.1275.

5′H-Spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one (7e). Orange solid, yield: 132 mg (82%); mp 130–132 °C; IR (CHCl₃) ν_max: 3332, 3193, 1716, 1616, 1508, 1452, 1321, 1198, 735 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.26 (s, 1H, NH), 8.07 (d, J = 8.54 Hz, 1H, ArH), 7.98 (dd, J₁ = 7.32 Hz, J₂ = 1.83 Hz, 1H, ArH), 7.51 (d, J = 7.93 Hz, 1H, ArH), 7.41–7.45 (m, 1H, ArH), 7.24–7.33 (m, 2H, ArH), 7.16 (t, J = 7.93 Hz, 1H, ArH), 7.05–7.09 (m, 2H, ArH), 7.00–7.04 (m, 1H, ArH), 6.83 (dd, J₁ = 7.32 Hz, J₂ = 1.83 Hz, 1H, ArH), 6.76 (d, J = 7.93 Hz, 1H, ArH), 6.00 (s, 1H, pyrrolic H), 4.35 (s, 1H, NH); ¹³C NMR (100 MHz, CDCl₃): 177.4, 141.1, 138.5, 134.8, 130.3, 129.6, 129.3, 127.1, 125.8, 124.1, 123.3, 123.1, 121.3, 121.0, 120.1, 116.2, 116.1, 112.6, 112.1, 110.8, 100.7, 61.6; HRMS (ESI, m/z) calcd for C₂₂H₁₅N₃NaO: 360.1107 [M + Na]⁺, found: 360.1115.

1-Methyl-5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one (7f). Orange solid, yield: 132 mg (79%); mp 200–202 °C; IR (CHCl₃) ν_max: 3356, 2934, 1715, 1611, 1472, 1342, 1238, 1095, 762, 738 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.06 (d, J = 8.54 Hz, 1H, ArH), 7.97–7.99 (m, 1H, ArH), 7.50 (d, J = 7.32 Hz, 1H, ArH), 7.38–7.46 (m, 2H, ArH), 7.25–7.32 (m, 1H, ArH), 7.13 (t, J = 7.93 Hz, 2H, ArH), 7.04–7.07 (m, 2H, ArH), 6.91 (d, J = 7.93 Hz, 1H, ArH), 6.84–6.86 (m, 1H, ArH), 5.97 (s, 1H, pyrrolic H), 4.13 (s, 1H, NH), 3.14 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): 174.6, 151.2, 143.9, 138.2, 134.9, 130.4, 129.2, 127.4, 125.7, 124.0, 123.3, 123.0, 121.1, 120.9, 120.3, 116.4, 116.0, 112.0, 109.7, 108.4, 100.2, 61.0, 26.1; HRMS (ESI, m/z) calcd for C₂₃H₁₈N₃O: 352.1444 [M + H]⁺, found: 352.1439.

5-Methyl-5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one (7g). Orange solid, yield: 134 mg (80%); mp 155–157 °C; IR (CHCl₃) ν_max: 3343, 3248, 1719, 1625, 1490, 1454, 1324, 1300, 1198, 745 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.08 (d, J = 8.54 Hz, 1H, ArH), 7.99 (dd, J₁ = 7.32 Hz, J₂ = 1.83 Hz, 1H, ArH), 7.88 (s, 1H, NH), 7.52 (d, J = 7.32 Hz, 1H, ArH), 7.28–7.32 (m, 1H, ArH), 7.14–7.17 (m, 2H, ArH), 7.02–7.09 (m, 3H, ArH), 6.82–6.84 (m, 1H, ArH), 6.69 (d, J = 7.93 Hz, 1H, ArH), 6.01 (s, 1H, pyrrolic H), 4.30 (s, 1H, NH), 2.29 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): 177.4, 138.7, 134.9, 134.7, 134.6, 132.8, 130.6, 129.7, 129.3, 127.1, 126.3, 124.1, 123.0, 121.2, 121.0, 120.0, 116.2, 116.0, 112.2, 110.5, 100.6, 61.7, 21.0; HRMS (ESI, m/z) calcd for C₂₃H₁₈N₃O: 352.1444 [M + H]⁺, found: 352.1454.

5-Chloro-5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one (7h). Orange solid, yield: 147 mg (83%); mp 264–266 °C; IR (CHCl₃) ν_max: 3327, 3266, 1733, 1718, 1685, 1508, 1453, 1194, 827, 736 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.73 (s, 1H, NH), 8.03 (d, J = 8.54 Hz, 1H, ArH), 7.93 (d, J = 7.32 Hz, 1H, ArH), 7.49 (d, J = 7.93 Hz, 1H, ArH), 7.29–7.33 (m, 1H, ArH), 7.14–7.19 (m, 2H, ArH), 6.94–7.08 (m, 3H, ArH), 6.73 (d, J = 7.93 Hz, 1H, ArH), 6.42 (d, J = 8.54 Hz, 1H, ArH), 5.95 (s, 1H, ArH), 4.39 (s, 1H, NH); HRMS (ESI, m/z) calcd for C₂₂H₁₅ClN₃O: 372.0898 [M + H]⁺, found: 372.0893.

5-Chloro-7′-methyl-5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one (7i). Orange solid, yield: 150 mg (87%); mp 149–151 °C; IR (CHCl₃) ν_max: 3344, 3235, 2922, 1731, 1705, 1616, 1455, 1384, 1322, 1235, 736 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.46 (s, 1H, NH), 8.24 (s, 1H, ArH), 8.04 (d, J = 8.54 Hz, 1H, ArH), 7.95 (d, J = 7.32 Hz, 1H, ArH), 7.58 (d, J = 7.93 Hz, 1H, ArH), 7.47–7.51 (m, 1H, ArH), 7.28–7.33 (m, 1H, ArH), 7.15–7.23 (m, 1H, ArH), 7.05–7.11 (m, 1H, ArH), 7.00–7.03 (m, 2H, ArH), 6.90 (d, J = 7.93 Hz, 1H, ArH), 6.80–6.85 (m, 1H, ArH), 4.30 (s, 1H, NH), 1.68 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): 177.1, 159.6, 149.4, 140.7, 138.4, 134.0, 133.6, 129.1, 127.0, 123.6, 123.3, 123.2, 120.5, 120.2, 119.1, 116.0, 115.9, 112.6, 112.2, 110.8, 109.0, 62.0, 8.2; HRMS (ESI, m/z) calcd for C₂₃H₁₈N₃O: 350.1289 [M − Cl]⁺, found: 350.1288.

1,7′-Dimethyl-5′H-spiro[indoline-3,6′-indolo[1,2-a]quinoxalin]-2-one (7j). Orange solid, yield: 129 mg (79%); mp 88–90 °C; IR (CHCl₃) ν_max: 3315, 3053, 2922, 1717, 1610, 1492, 1455, 1363, 1093, 738 cm⁻¹; ¹H NMR (400 MHz, CDCl₃): δ (ppm) 8.24 (d, J = 8.70, 1H, ArH), 8.16 (d, J = 7.79 Hz, 1H, ArH), 7.69–7.78 (m, 2H, ArH), 7.59 (t, J = 7.73 Hz, 1H, ArH), 7.49–7.53 (m, 1H, ArH), 7.43–7.46 (m, 1H, ArH), 7.36–7.39 (m, 1H, ArH), 7.27–7.31 (m, 1H, ArH), 7.19–7.24 (m, 1H, ArH), 7.13 (d, J = 7.79 Hz, 1H, ArH), 7.03 (d, J = 7.79 Hz, 1H, ArH), 4.47 (s, 1H, NH), 3.44 (s, 3H, CH₃) 3.40 (s, 3H, CH₃); ¹³C NMR (100 MHz, CDCl₃): 174.3, 151.2, 143.3, 138.2, 134.0, 130.2, 129.4, 127.2, 125.3, 123.5, 123.3, 123.0, 120.4, 120.3, 118.9, 116.1, 116.0, 112.0, 109.8, 108.5, 108.3, 61.5, 26.2, 8.1; HRMS (ESI, m/z) calcd for C₂₄H₁₉N₃NaO 388.1420 [M + Na]⁺, found: 388.1426.

Acknowledgements

This work is supported by University of Delhi, India under the scheme to strengthen R&D Doctoral Research Programme. We are thankful to Central Instrumentation Facility, University of Delhi, India for providing NMR, mass and single crystal X-ray data. Amreeta Preetam is grateful to CSIR, New Delhi, India for providing SRF.

Notes and references

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22. ESI.†.
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Footnote

† Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra of the synthesized products. CCDC 1014749. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra16651e

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