Simple and Highly Efficient Synthesis of Indolo- and Pyrrolo[1,2-a]quinoxalines Promoted by Molecular Iodine

Abstract

A simple and highly efficient strategy is developed for the synthesis of indolo- and pyrrolo[1,2-a]quinoxalines from the corresponding 2-(1H-indol/pyrrol-1-yl)anilines promoted by molecular iodine in good to excellent yields.

Quinoxalines constitute an important class of nitrogen-containing heterocyclic compounds that display useful physiological effects and a wide spectrum of biological activities.[2] They exhibit potential antitumor, antifungal, and anti-HIV activities and also act as glucagon and angiotensin receptor antagonists.[3] Quinoxalines also possess second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) and VEGFR-3 kinase inhibitor activity and display fluorescence properties for amyloid fibril detection.[4] The quinoxaline moiety is also a part of a number of antibiotics.[5] Novel quinoxaline-based organic sensitizers have also been used for dye-sensitized solar cells (DSSCs).[6]

Pyrrolo[1,2-a]quinoxalines may be synthesized in two steps from 1-(2-aminophenyl)pyrroles.[7] [8] [9] Reaction of the 1-(2-aminophenyl)pyrrole with alkyl or aryl acid chlorides affords the corresponding acetamides, which, upon intramolecular cyclization under Bischler–Napieralski conditions, provide the corresponding pyrrolo[1,2-a]quinoxalines.[7] Sharma et al. reported the one-pot synthesis of 4-aryl pyrrolo[1,2-a]quinoxalines from 1-(2-aminophenyl)pyrroles and aromatic aldehydes by a modified Pictet–Spengler reaction using cyanuric chloride.[8] Similarly, Verma et al. reported the synthesis using AlCl₃ and benzotriazole (Scheme [1]).[9] Pereira et al. reported a one-pot synthesis using 1-(2-nitrophenyl)pyrrole and an excess of alcohol under redox reaction conditions with iron (9 equiv) and 12 M hydrochloric acid (11 equiv).[10] However, these synthetic routes suffer from harsh reaction conditions and low yields. Thus, the development of a novel and efficient strategy that allows the construction of this fused heterocyclic motif is highly desirable.

Molecular iodine has been extensively used as an inexpensive and readily available mild Lewis acid catalyst[11] for esterification and selective protection of alcohols,[12] acetylation,[13] protection[14] or deprotection[15] of acetals, N-Boc protection of amines,[16] and Michael addition reactions.[17] Iodine in alcohol has also been used for the aromatization of several α,β-unsaturated ketones and esters.[18] Iodine also acts as a mild oxidizing reagent to generate carbonyl compounds from alcohols[19] and also facilitates mild and efficient methods for C–C and C–N bond formation.[20]

Narender et al. have reported a molecular iodine-promoted oxidative dimerization of benzylamines to their corresponding imines and further application in the synthesis of benzimidazoles and benzothiazoles.[21] As part of our ongoing research towards the development of novel methodologies for the synthesis of heterocyclic compounds,[22] we report herein an efficient synthesis of various indolo- and pyrrolo[1,2-a]quinoxalines starting from 1-(2-aminophenyl)pyrroles/indoles and substituted benzylamines under mild reaction conditions and in excellent yields by using molecular iodine.

Table 1 Optimization of Reaction Conditions for the Synthesis of Pyrrolo[1,2-a]quinoxalines^a

Entry	Iodine (equiv)	Solvent	T (°C)	t (h)	Yield (%)b
1	1.0	MeCN	25	48	60
2	1.0	EtOAc	25	48	48
3	1.0	THF	25	48	55
4	1.0	CH2Cl2	25	48	42
5	1.0	toluene	25	48	23
6	1.0	DMSO	25	48	15
7	1.5	MeCN	25	48	70
8	2.0	MeCN	25	48	80
9	2.5	MeCN	25	48	76
10	2.0	MeCN	80	6	90

^a Reaction conditions: 1a (1.58 mmol), 2a (3.16 mmol), solvent (10 mL).

^b Isolated yield.

As a starting point, 1-(2-aminophenyl)pyrrole (1a) and benzylamine (2a) were reacted in the presence of molecular iodine, and factors such as solvent, temperature, and molar equivalents of iodine were varied (Table [1]). The initial experiment using 1.0 equivalent of iodine in acetonitrile at room temperature gave the expected quinoxaline derivative 3a in 60% yield (Table [1], entry 1). Different solvents, including EtOAc, THF, CH₂Cl₂, toluene and DMSO, were screened but product formation was considerably lower than that obtained by using acetonitrile (entries 2–6). The influence of the amount of iodine was screened in acetonitrile, and the highest yield (80%) was obtained when 2.0 equivalents of iodine (entry 7–9) was used. The effect of temperature was also investigated and the reaction conversion rate was found to improve greatly when the reaction was conducted at 80 °C in acetonitrile; under these conditions, the reaction was complete in six hours and gave 3a in 90% yield (entry 10).

With optimal reaction conditions established, we tested the scope and effectiveness of the above process with a variety of substituted benzylamines and substituted 1-(2-aminophenyl)pyrroles (Table [2]). Interestingly, irrespective of the presence of electron-donating or electron-withdrawing groups on these substrates, the corresponding pyrrolo[1,2-a]quinoxalines were obtained in good to excellent yields (entries 1–5 and 9–17). Increased substitution on the benzylamine also had no significant impact on either the required reaction time or product yield (entries 6–8).

Table 2 Iodine-Mediated Synthesis of Pyrrolo[1,2-a]quinoxalines under the Optimized Conditions

Entry	1	R1	2	R2	3	Time (h)	Yield (%)a
1	1a	H	2a	H	3a	6	90
2	1a	H	2b	2-Me	3b	5	87
3	1a	H	2c	4-Cl	3c	6	84
4	1a	H	2d	4-MeO	3d	5	90
5	1a	H	2e	4-CN	3e	8	87
6	1a	H	2f	4-Ph	3f	5	82
7	1a	H	2g	3-F-5-Me	3g	7	91
8	1a	H	2h	3-F-5-F3C	3h	7	92
9	1b	Me	2a	H	3i	5	88
10	1b	Me	2b	2-Me	3j	5	86
11	1b	Me	2c	4-Cl	3k	6	91
12	1b	Me	2d	4-MeO	3l	5	91
13	1b	Me	2e	4-CN	3m	8	87
14	1c	Cl	2b	2-Me	3n	6	88
15	1c	Cl	2c	4-Cl	3o	7	93
16	1c	Cl	2d	4-MeO	3p	5	92
17	1c	Cl	2e	4-CN	3q	8	82

^a Isolated yield.

To further establish the scope of this methodology, coupling of 1-(2-aminophenyl)indole (4) with substituted benzylamines was studied (Table [3]) under similar reaction conditions. In this case, the corresponding indolo[1,2-a]quinoxalines 5a–e were produced in excellent yields (entries 1–5).

Table 3 Synthesis of Indolo[1,2-a]quinoxalines under the Optimized Conditions

Entry	2	R2	5	Time (h)	Yield (%)a
1	2a	H	5a	7	94
2	2a	H	5b	6	89
3	2c	4-Cl	5c	7	95
4	2d	4-MeO	5d	5	94
5	2e	4-CN	5e	8	83

^a Isolated yield.

A plausible mechanism for the formation of pyrrolo[1,2-a]quinoxalines is illustrated in Scheme [2]. Based on previous reports,[21] benzylamine undergoes oxidative dimerization in the presence of iodine to afford the corresponding imine intermediate I. Transimination of I with 1-(2-aminophenyl)pyrrole gives imine intermediate II, which, upon cyclization followed by oxidation, produces the desired pyrrolo[1,2-a]quinoxaline.

To find support for the above mechanism, benzylamine (2a) was treated with iodine in acetonitrile and the intermediate imine I was isolated; the structure of the latter was confirmed by comparison with previously reported data (Scheme [3]).[23] Imine intermediate I was then treated with 1-(2-aminophenyl)pyrrole (1a) in the presence of iodine in acetonitrile at 80 °C to furnish the desired product 3a. However, our attempts to isolate the intermediates II and III under the reaction conditions were unsuccessful, and we could only detect a mixture of 3a, 1a, and intermediate I, indicating that intermediates II and III are transient and readily converted into 3a. Thus, intermediate II was prepared separately by reaction between benzylamine (2a) and benzaldehyde (6) in the presence of basic Al₂O₃.[23] The isolated intermediate II was then subjected to cyclization in the presence of iodine to afford the expected product 3a.

In conclusion, we have demonstrated a facile and highly efficient strategy for the synthesis of indolo- and pyrrolo[1,2-a]quinoxalines from the corresponding 1-(2-aminophenyl)pyrroles and 1-(2-aminophenyl)indoles promoted by molecular iodine.[24] A large number of indolo- and pyrrolo[1,2-a]quinoxalines was obtained in good to excellent yields.

Acknowledgment

The authors are grateful to Dr. Upadhya Timmanna and Dr. Vilas H. Dahanukar for their constant encouragement and support. We also thank the analytical department of Dr. Reddy’s Laboratories for providing analytical support.

• References and Notes

• 1 Dr. Reddy’s Laboratories Ltd. communication No: IPDO IPM-00421.
• 2 Antoniotti S, Dunach E. Tetrahedron Lett. 2002; 43: 3971
  CrossrefSearch in Google Scholar
• 3a Alleca S, Corona P, Lorigo M, Paglietti G, Loddo R, Mascia V, Busonera B, La Colla P. Farmaco 2003; 58: 639
  CrossrefPubMedSearch in Google Scholar
• 3b Patel M, Mc Hugh RJ, Cordova BC, Klabe RM, Erickson-Vitanen S, Trainor GL, Rodger JD. Bioorg. Med. Chem. Lett. 2000; 10: 1729
  CrossrefPubMedSearch in Google Scholar
• 3c Guillon J, Dallemagne P, Pfeiffer B, Renard P, Manechez D, Kervran A, Rault S. Eur. J. Med. Chem. 1998; 33: 293
  CrossrefSearch in Google Scholar
• 3d Kim KS, Qian L, Bird JE, Dickinson KE. J, Moreland S, Schaeffer TR, Waldron TL, Delaney CL, Weller HN, Miller AV. J. Med. Chem. 1999; 36: 2335
  Search in Google Scholar
• 3e Jacobsen EJ, Stelzer LS, Belonga KL, Carter DB, Im WB, Sethy VH, Tang AH, Von-Voigtlander PF, Petke JD. J. Med. Chem. 1996; 39: 3820
  CrossrefPubMedSearch in Google Scholar
• 4a Prunier H, Rault S, Lancelot JC, Robba M, Renard P, Delagrange P, Pfeiffer B, Caignard DH, Misslin R, Lemaitre BG, Hamon M. J. Med. Chem. 1997; 40: 1808
  CrossrefPubMedSearch in Google Scholar
• 4b Butini S, Budriesi R, Hamon M, Morelli E, Gemma S, Brindisi M, Borrelli G, Novellino E, Fiorini I, Ioan P, Chiarini A, Cagnotto A, Mennini T, Fracasso C, Caccia S, Campiani G. J. Med. Chem. 2009; 52: 6946
  CrossrefPubMedSearch in Google Scholar
• 4c Guillon J, Grellier P, Labaied M, Sonnet P, Leger JM, Deprez-Poulain R, Forfar-Bares I, Dallemagne P, Lemaitre N, Pehourcq F, Rochette J, Sergheraert C, Jarry C. J. Med. Chem. 2004; 47: 1997
  CrossrefPubMedSearch in Google Scholar
• 4d Gemma S, Colombo L, Forloni G, Savini L, Fracasso C, Caccia S, Salmona M, Brindisi M, Joshi BP, Tripaldi P, Giorgi G, Taglialatela-Scafati O, Novellino E, Fiorini I, Campiani G, Butini S. Org. Biomol. Chem. 2011; 9: 5137
  CrossrefPubMedSearch in Google Scholar
• 4e Desplat V, Geneste A, Begorre MA, Fabre SB, Brajot S, Massip S, Thiolat D, Mossalayi D, Jarry C, Guillon J. J. Enzyme Inhib. Med. Chem. 2008; 23: 648
  CrossrefSearch in Google Scholar
• 4f Desplat V, Moreau S, Gay A, Fabre SB, Thiolat D, Massip S, Macky G, Godde F, Mossalayi D, Jarry C, Guillon J. J. Enzyme Inhib. Med. Chem. 2010; 25: 204
  CrossrefPubMedSearch in Google Scholar
• 5 Bailly C, Echepare S, Gago F. Anti-Cancer Drug Des. 1999; 14: 291
  Search in Google Scholar
• 6a Lin TC, Lee YH, Liu CY, Huang BR, Tsai MY, Huang YJ, Lin JH, Shen YK, Wu CY. Chem. Eur. J. 2013; 19: 749
  CrossrefSearch in Google Scholar
• 6b Chang DW, Lee HJ, Kim JH, Park SY, Park SM, Dai L, Baek JB. Org. Lett. 2011; 13: 3880
  CrossrefSearch in Google Scholar
• 7a Cheeseman GW. H, Tuck B. J. Chem. Soc. C 1966; 852
  Crossref
• 7b Guillon J, Forfar I, Mamani-Matsuda M, Desplat V, Saliege M, Thiolat D, Massip S, Tabourier A, Leger JM, Dufaure B, Haumont G, Jarry C, Mossalayi D. Bioorg. Med. Chem. 2007; 15: 194
  CrossrefPubMedSearch in Google Scholar
• 7c Kalinin AA, Mamedov VA. Chem. Heterocycl. Compd. 2011; 46: 1423
  CrossrefSearch in Google Scholar
• 7d Lancelot JC, Rault S, Laduree D, Robba M. Chem. Pharm. Bull. 1985; 33: 2798
  CrossrefSearch in Google Scholar
• 7e Guillon J, Dumoulin H, Dallemagne P, Reynolds R, Rault S. Pharm. Pharmacol. Commun. 1998; 4: 33
  Search in Google Scholar
• 8 Sharma A, Singh M, Rai N, Sawant D. Beilstein J. Org. Chem. 2013; 9: 1235
  CrossrefSearch in Google Scholar
• 9 Verma AK, Jha RR, Sankar VK, Aggarwal T, Singh RP, Chandra R. Eur. J. Org. Chem. 2011; 6998
• 10 Pereira Mde F, Thiery V. Org. Lett. 2012; 14: 754
  Search in Google Scholar
• 11a Zmitek K, Zupan M, Stavber S, Iskra J. J. Org. Chem. 2007; 72: 6534
  CrossrefSearch in Google Scholar
• 11b Ren YM, Cai C. Org. Prep. Proced. Int. 2008; 40: 101
  CrossrefSearch in Google Scholar
• 11c Zmitek K, Zupan M, Stavber S, Iskra J. Org. Lett. 2006; 8: 2491
  CrossrefSearch in Google Scholar
• 12a Ramalinga K, Vijayalakshmi P, Kaimal TN. B. Tetrahedron Lett. 2002; 43: 879
  CrossrefSearch in Google Scholar
• 12b Deka N, Sarma JC. J. Org. Chem. 2001; 66: 1947
  CrossrefPubMedSearch in Google Scholar
• 13 Deka N, Mariotte AM, Boumendjel A. Green Chem. 2001; 3: 263
  CrossrefSearch in Google Scholar
• 14 Karimi B, Golshani B. Synthesis 2002; 784
• 15 Sun J, Dong Y, Cao L, Wang X, Wang S, Hu Y. J. Org. Chem. 2004; 69: 8932
  CrossrefSearch in Google Scholar
• 16 Varala R, Nuvula S, Adapa SR. J. Org. Chem. 2006; 71: 8283
  CrossrefPubMedSearch in Google Scholar
• 17a Yadav JS, Reddy BV. S, Sadasiv K, Satheesh G. Tetrahedron Lett. 2002; 43: 9695
  CrossrefSearch in Google Scholar
• 17b Wang SY, Ji SJ, Loh TP. Synlett 2003; 2377
  Thieme Connect
• 18a Kotins AS. Tetrahedron Lett. 1990; 31: 481
  CrossrefSearch in Google Scholar
• 18b Kim JM, Lee KY, Kim JN. Bull. Korean Chem. Soc. 2003; 24: 1057
  CrossrefSearch in Google Scholar
• 19a Miller RA, Hoerrner RS. Org. Lett. 2003; 5: 285
  CrossrefPubMedSearch in Google Scholar
• 19b Mori N, Togo H. Synlett 2004; 880
• 19c Mori N, Togo H. Tetrahedron 2005; 61: 5915
  CrossrefSearch in Google Scholar
• 19d Gogoi P, Konwar D. Org. Biomol. Chem. 2005; 3: 3473
  CrossrefSearch in Google Scholar
• 20 Togo H, Iida S. Synlett 2006; 2159
  Thieme Connect
• 21 Naresh G, Kant R, Narender T. J. Org. Chem. 2014; 79: 3821
  CrossrefSearch in Google Scholar
• 22 Ramamohan M, Raghunadh A, Raghavendrarao K, Chandrashekar KB, Sridhar R, Jayaprakash S. Synlett 2014; 25: 821
  Thieme ConnectSearch in Google Scholar
• 23 Boullet FT. Synthesis 1985; 679
  Thieme Connect
• 24 Synthesis of Indolo- and Pyrrolo[1,2-a]quinoxalines; General Procedure: To a stirred solution of benzylamine (338 mg, 3.16 mmol) in MeCN (10 mL) was added iodine (800 mg, 3.16 mmol) followed by 1-(2-aminophenyl)pyrrole (250 mg, 1.58 mmol) at room temperature. The reaction mixture was heated to 80 °C and stirred for 5–8 h, with the progress of the reaction being monitored by TLC. Upon completion, the reaction mixture was allowed to cool to room temperature and excess iodine was quenched by the addition of sat. aq Na₂S₂O₃. The mixture was extracted with ethyl acetate (10 mL), and the organic layer was dried over anhydrous Na₂SO₄, filtered, and the solvent was removed to give the crude product, which was further purified by silica-gel column chromatography (hexane–EtOAc, 4:1) to afford the desired product. 4-Phenylpyrrolo[1,2-a]quinoxaline (3a): Yield: 347 mg (90%); pale-yellow solid; mp 117–119 °C; IR (KBr): 3435, 3064, 2918, 1602, 1532, 1522, 1475, 1445, 1416, 1370, 1322, 1251, 1167, 1096, 1073, 912, 933, 752, 710, 688 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 6.87 (t, J = 3.0 Hz, 1 H), 6.98 (d, J = 3.2 Hz, 1 H), 7.55–7.42 (m, 5 H), 7.86 (d, J = 8.0 Hz, 1 H), 8.04–7.97 (m, 4 H); ¹³C NMR (100 MHz, CDCl₃): δ = 108.6, 113.6, 114.0, 114.5, 125.2, 125.4, 127.1, 127.4, 128.5, 128.6, 129.7, 130.2, 136.2, 138.4, 154.4; MS: m/z = 245.2 [M + H]; HRMS (ESI): m/z [M + H] calcd. for C₁₇H₁₃N₂: 245.1079; found: 245.1079.

• References and Notes

• 1 Dr. Reddy’s Laboratories Ltd. communication No: IPDO IPM-00421.
• 2 Antoniotti S, Dunach E. Tetrahedron Lett. 2002; 43: 3971
  CrossrefSearch in Google Scholar
• 3a Alleca S, Corona P, Lorigo M, Paglietti G, Loddo R, Mascia V, Busonera B, La Colla P. Farmaco 2003; 58: 639
  CrossrefPubMedSearch in Google Scholar
• 3b Patel M, Mc Hugh RJ, Cordova BC, Klabe RM, Erickson-Vitanen S, Trainor GL, Rodger JD. Bioorg. Med. Chem. Lett. 2000; 10: 1729
  CrossrefPubMedSearch in Google Scholar
• 3c Guillon J, Dallemagne P, Pfeiffer B, Renard P, Manechez D, Kervran A, Rault S. Eur. J. Med. Chem. 1998; 33: 293
  CrossrefSearch in Google Scholar
• 3d Kim KS, Qian L, Bird JE, Dickinson KE. J, Moreland S, Schaeffer TR, Waldron TL, Delaney CL, Weller HN, Miller AV. J. Med. Chem. 1999; 36: 2335
  Search in Google Scholar
• 3e Jacobsen EJ, Stelzer LS, Belonga KL, Carter DB, Im WB, Sethy VH, Tang AH, Von-Voigtlander PF, Petke JD. J. Med. Chem. 1996; 39: 3820
  CrossrefPubMedSearch in Google Scholar
• 4a Prunier H, Rault S, Lancelot JC, Robba M, Renard P, Delagrange P, Pfeiffer B, Caignard DH, Misslin R, Lemaitre BG, Hamon M. J. Med. Chem. 1997; 40: 1808
  CrossrefPubMedSearch in Google Scholar
• 4b Butini S, Budriesi R, Hamon M, Morelli E, Gemma S, Brindisi M, Borrelli G, Novellino E, Fiorini I, Ioan P, Chiarini A, Cagnotto A, Mennini T, Fracasso C, Caccia S, Campiani G. J. Med. Chem. 2009; 52: 6946
  CrossrefPubMedSearch in Google Scholar
• 4c Guillon J, Grellier P, Labaied M, Sonnet P, Leger JM, Deprez-Poulain R, Forfar-Bares I, Dallemagne P, Lemaitre N, Pehourcq F, Rochette J, Sergheraert C, Jarry C. J. Med. Chem. 2004; 47: 1997
  CrossrefPubMedSearch in Google Scholar
• 4d Gemma S, Colombo L, Forloni G, Savini L, Fracasso C, Caccia S, Salmona M, Brindisi M, Joshi BP, Tripaldi P, Giorgi G, Taglialatela-Scafati O, Novellino E, Fiorini I, Campiani G, Butini S. Org. Biomol. Chem. 2011; 9: 5137
  CrossrefPubMedSearch in Google Scholar
• 4e Desplat V, Geneste A, Begorre MA, Fabre SB, Brajot S, Massip S, Thiolat D, Mossalayi D, Jarry C, Guillon J. J. Enzyme Inhib. Med. Chem. 2008; 23: 648
  CrossrefSearch in Google Scholar
• 4f Desplat V, Moreau S, Gay A, Fabre SB, Thiolat D, Massip S, Macky G, Godde F, Mossalayi D, Jarry C, Guillon J. J. Enzyme Inhib. Med. Chem. 2010; 25: 204
  CrossrefPubMedSearch in Google Scholar
• 5 Bailly C, Echepare S, Gago F. Anti-Cancer Drug Des. 1999; 14: 291
  Search in Google Scholar
• 6a Lin TC, Lee YH, Liu CY, Huang BR, Tsai MY, Huang YJ, Lin JH, Shen YK, Wu CY. Chem. Eur. J. 2013; 19: 749
  CrossrefSearch in Google Scholar
• 6b Chang DW, Lee HJ, Kim JH, Park SY, Park SM, Dai L, Baek JB. Org. Lett. 2011; 13: 3880
  CrossrefSearch in Google Scholar
• 7a Cheeseman GW. H, Tuck B. J. Chem. Soc. C 1966; 852
  Crossref
• 7b Guillon J, Forfar I, Mamani-Matsuda M, Desplat V, Saliege M, Thiolat D, Massip S, Tabourier A, Leger JM, Dufaure B, Haumont G, Jarry C, Mossalayi D. Bioorg. Med. Chem. 2007; 15: 194
  CrossrefPubMedSearch in Google Scholar
• 7c Kalinin AA, Mamedov VA. Chem. Heterocycl. Compd. 2011; 46: 1423
  CrossrefSearch in Google Scholar
• 7d Lancelot JC, Rault S, Laduree D, Robba M. Chem. Pharm. Bull. 1985; 33: 2798
  CrossrefSearch in Google Scholar
• 7e Guillon J, Dumoulin H, Dallemagne P, Reynolds R, Rault S. Pharm. Pharmacol. Commun. 1998; 4: 33
  Search in Google Scholar
• 8 Sharma A, Singh M, Rai N, Sawant D. Beilstein J. Org. Chem. 2013; 9: 1235
  CrossrefSearch in Google Scholar
• 9 Verma AK, Jha RR, Sankar VK, Aggarwal T, Singh RP, Chandra R. Eur. J. Org. Chem. 2011; 6998
• 10 Pereira Mde F, Thiery V. Org. Lett. 2012; 14: 754
  Search in Google Scholar
• 11a Zmitek K, Zupan M, Stavber S, Iskra J. J. Org. Chem. 2007; 72: 6534
  CrossrefSearch in Google Scholar
• 11b Ren YM, Cai C. Org. Prep. Proced. Int. 2008; 40: 101
  CrossrefSearch in Google Scholar
• 11c Zmitek K, Zupan M, Stavber S, Iskra J. Org. Lett. 2006; 8: 2491
  CrossrefSearch in Google Scholar
• 12a Ramalinga K, Vijayalakshmi P, Kaimal TN. B. Tetrahedron Lett. 2002; 43: 879
  CrossrefSearch in Google Scholar
• 12b Deka N, Sarma JC. J. Org. Chem. 2001; 66: 1947
  CrossrefPubMedSearch in Google Scholar
• 13 Deka N, Mariotte AM, Boumendjel A. Green Chem. 2001; 3: 263
  CrossrefSearch in Google Scholar
• 14 Karimi B, Golshani B. Synthesis 2002; 784
• 15 Sun J, Dong Y, Cao L, Wang X, Wang S, Hu Y. J. Org. Chem. 2004; 69: 8932
  CrossrefSearch in Google Scholar
• 16 Varala R, Nuvula S, Adapa SR. J. Org. Chem. 2006; 71: 8283
  CrossrefPubMedSearch in Google Scholar
• 17a Yadav JS, Reddy BV. S, Sadasiv K, Satheesh G. Tetrahedron Lett. 2002; 43: 9695
  CrossrefSearch in Google Scholar
• 17b Wang SY, Ji SJ, Loh TP. Synlett 2003; 2377
  Thieme Connect
• 18a Kotins AS. Tetrahedron Lett. 1990; 31: 481
  CrossrefSearch in Google Scholar
• 18b Kim JM, Lee KY, Kim JN. Bull. Korean Chem. Soc. 2003; 24: 1057
  CrossrefSearch in Google Scholar
• 19a Miller RA, Hoerrner RS. Org. Lett. 2003; 5: 285
  CrossrefPubMedSearch in Google Scholar
• 19b Mori N, Togo H. Synlett 2004; 880
• 19c Mori N, Togo H. Tetrahedron 2005; 61: 5915
  CrossrefSearch in Google Scholar
• 19d Gogoi P, Konwar D. Org. Biomol. Chem. 2005; 3: 3473
  CrossrefSearch in Google Scholar
• 20 Togo H, Iida S. Synlett 2006; 2159
  Thieme Connect
• 21 Naresh G, Kant R, Narender T. J. Org. Chem. 2014; 79: 3821
  CrossrefSearch in Google Scholar
• 22 Ramamohan M, Raghunadh A, Raghavendrarao K, Chandrashekar KB, Sridhar R, Jayaprakash S. Synlett 2014; 25: 821
  Thieme ConnectSearch in Google Scholar
• 23 Boullet FT. Synthesis 1985; 679
  Thieme Connect
• 24 Synthesis of Indolo- and Pyrrolo[1,2-a]quinoxalines; General Procedure: To a stirred solution of benzylamine (338 mg, 3.16 mmol) in MeCN (10 mL) was added iodine (800 mg, 3.16 mmol) followed by 1-(2-aminophenyl)pyrrole (250 mg, 1.58 mmol) at room temperature. The reaction mixture was heated to 80 °C and stirred for 5–8 h, with the progress of the reaction being monitored by TLC. Upon completion, the reaction mixture was allowed to cool to room temperature and excess iodine was quenched by the addition of sat. aq Na₂S₂O₃. The mixture was extracted with ethyl acetate (10 mL), and the organic layer was dried over anhydrous Na₂SO₄, filtered, and the solvent was removed to give the crude product, which was further purified by silica-gel column chromatography (hexane–EtOAc, 4:1) to afford the desired product. 4-Phenylpyrrolo[1,2-a]quinoxaline (3a): Yield: 347 mg (90%); pale-yellow solid; mp 117–119 °C; IR (KBr): 3435, 3064, 2918, 1602, 1532, 1522, 1475, 1445, 1416, 1370, 1322, 1251, 1167, 1096, 1073, 912, 933, 752, 710, 688 cm^–1; ¹H NMR (400 MHz, CDCl₃): δ = 6.87 (t, J = 3.0 Hz, 1 H), 6.98 (d, J = 3.2 Hz, 1 H), 7.55–7.42 (m, 5 H), 7.86 (d, J = 8.0 Hz, 1 H), 8.04–7.97 (m, 4 H); ¹³C NMR (100 MHz, CDCl₃): δ = 108.6, 113.6, 114.0, 114.5, 125.2, 125.4, 127.1, 127.4, 128.5, 128.6, 129.7, 130.2, 136.2, 138.4, 154.4; MS: m/z = 245.2 [M + H]; HRMS (ESI): m/z [M + H] calcd. for C₁₇H₁₃N₂: 245.1079; found: 245.1079.

• Supplementary Material