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Green Chemistry Letters and Reviews Volume 6, 2013 - Issue 3
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RESEARCH LETTERS

An expeditious synthesis of quinoxalines by using biodegradable cellulose sulfuric acid as a solid acid catalyst

B. Suresh Kuarm Department of Chemistry, National Institute of Technology, Warangal, India
,
Peter A. Crooks Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR, USA
&
B. Rajitha Department of Chemistry, National Institute of Technology, Warangal, IndiaCorrespondence[email protected]
Pages 228-232 | Received 25 Jul 2010, Accepted 14 Nov 2012, Published online: 18 Feb 2013

Abstract

A simple, efficient and environmentally friendly process for the solid state synthesis of quinoxaline derivatives by the condensation reaction of the benzo[c][1,2,5]thiadiazole-4,5-diamine and 3-(ω-bromoacetyl)-coumarins in the presence of cellulose sulfuric acid by simple physical grinding of reactants using a mortar and pestle at room temperature in good to excellent yields with high purity. The catalyst is recyclable and reusable.

Introduction

Synthesis of quinoxaline and their derivatives has received much attention from organic and medicinal chemists because of their wide range applications in various fields, such as combinatorial drug discovery libraries Citation1, dyes Citation2, organic semiconductors Citation3, electron luminescent materials Citation4, cavitands Citation5, dehydroannulenes Citation6, DNA cleaving agents Citation7. On the other hand, literature surveys show that coumarin ring system Citation8 is biologically very important pharmacophore. From our laboratories dihydro quinoxaline chromenes Citation9 were reported under drastic conditions and yields were very poor. A number of methods has been developed for the synthesis of simple and substituted quinoxalines by oxidative coupling Citation10, MnO2 Citation11, POCl3 Citation12, ceric ammonium nitrate Citation13, iodine Citation14, montmorillonite K-10 Citation15, Ga(OTf)3 Citation16, silica gel Citation17, citric acid Citation18, Oxalic acid/EtOH Citation19, sulfated TiO2 Citation20, sulfated TiO2-P25 Citation21, acetic acid/copper catalyzed oxidative cyclization of α-hydroxy ketones with 1,2-diamines Citation22. Nevertheless, most of the reported methods suffer from one or more disadvantages in the process of synthesis which are unsatisfactory yields, longer reaction time, difficulties in product isolation process, moreover the use of highly expensive and detrimental metal precursors, drastic reaction conditions were observed and also no agreement with the green chemistry protocols, which limit their use. Hence it is highly essential to develop biodegradable, ecofriendly, green synthesis of quinoxaline.

Cellulose is one of the most abundant natural materials in the world and it has been widely studied during the past several decades because it is a biodegradable material and a renewable resource. Its unique properties make it an alternative to conventional organic or inorganic supports in catalytic applications. Recently, the approach has been shifting more toward eco-friendly and reusable catalysts. Recently, cellulose sulfuric acid has emerged as a solid acid catalyst for acid catalyzed reactions, such as synthesis of α-aminonitriles Citation23, imidazoazines Citation24, quinolines Citation25, aryl-14H-dibenzo [a.j] xanthenes Citation26, 3,4-dihydropyrimidine-2(1H)-ones Citation27, Pechmann condensation Citation28, thiadiazolo benzimidazoles Citation29, hexahydroxnthene Citation30, and quinazolines Citation31 . Cellulose sulfuric acid can be easily prepared by the reaction of inexpensive cellulose with chlorosulfonic acid.

Scheme 1.  A mixture of benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol), 2-(2-Bromo-acetyl)-benzo[f]chromen-3-one (3.0 mmol) and cellulose sulfuric acid (0.08g), r.t

Scheme 1.  A mixture of benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol), 2-(2-Bromo-acetyl)-benzo[f]chromen-3-one (3.0 mmol) and cellulose sulfuric acid (0.08g), r.t

Scheme 2.  A mixture of benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol), substituted 3-(ω-bromo acetyl)-coumarins (3.0 mmol) and cellulose sulfuric acid (0.08g), r.t, 30min

Scheme 2.  A mixture of benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol), substituted 3-(ω-bromo acetyl)-coumarins (3.0 mmol) and cellulose sulfuric acid (0.08g), r.t, 30min

Results and discussion

In continuation of our studies on cellulose sulfuric acid, we attempted the synthesis of quinoxaline derivatives by simple physical grinding of, benzo[c]Citation1 Citation2 Citation5thiadiazole-4, 5-diamine and 3-(ω-bromoacetyl)-coumarins in the presence of cellulose sulfuric acid using a mortar and pestle at room temperature.

Table 1. Yields of cellulose sulfuric acid catalyzed synthesis of quinoxalines.

We then investigated the efficiency of the cellulose sulfuric acid compared to various sulfur analog acidic catalysts. The results are summarized in . Cellulose sulfuric acid was found to be the most effective catalyst based on the product yield. The reaction did not proceed in the absence of catalyst (yield less than 15%).

Table 2. Effect of catalysts on yield.

We examined the amount of catalyst in this reaction. The best results were obtained using 0.08 g of catalyst (96%). Using lower amounts of catalyst resulted in lower yields, in the absence of catalyst the yield of the product was found to be very low ().

Table 3. Influence of the catalytic amounts of cellulose sulfuric acid.a

Experimental

Melting points are uncorrected and were determined in open capillaries. The reactions were monitored by thin layer chromatography (TLC) and visualized with UV light. IR spectra (KBr) were recorded on Shimadzu FTIR model 8010 spectrometer and the 1H NMR spectra on Varian Gemini 200 MHz spectrometer using TMS as an internal standard. Mass spectra were recorded on a JEOL JMS D-300 Spectrometer. The elemental analysis of the compounds was done on a Carlo Erba Model EA1108. All solvents and reagents were purchased from Aldrich and Fluka firms.

General procedure

A mixture of benzo[c]Citation1 Citation2 Citation5thiadiazole-4,5-diamine (3.0 mmol), 3-(ω-bromoacetyl)-coumarin (3.0 mmol) and cellulose sulfuric acid (0.08 g) was taken in a mortar, grinding with a pestle at room temperature for the appropriate time, as shown in . Completion of the reaction was indicated by TLC (2:8, ethyl acetate:hexane) monitoring. After completion of the reaction, ethyl acetate (10 mL) was added and the reaction mixture was washed with water (6 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated to dryness, and the crude solid product was further purified by column chromatography (hexane/ethyl acetate, 8:2). The aqueous layer containing the catalyst could be evaporated under reduced pressure to give a white solid. The recovered catalyst was washed with CH2Cl2, dried in an oven (50 mm Hg pressure) at 60°C for 5 h under high-pressure prior to use in the other reaction. The recovered catalyst can be reused at least three additional times in subsequent reactions without significant loss in product yield ().

Table 4. Yields of recovered catalyst.

Product characterization data

3-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-2H-chromen-2-one (3a)

Mp 245°C. IR (KBr, cm−1): 1610, 1720. 1H NMR (CDCl3): δ=7.31–7.85 (m, 6H), 8.18 (s, 1H), 9.18 (s, 1H); MS (EI): m/z=332(M). Anal. Calcd. for C17H8N4O2S: C, 61.44; H, 2.43; N, 16.86; Found: C, 61.32; H, 2.40; N, 16.92.

3-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-8-bromo-2H-chromen-2-one (3b)

Mp 215°C. IR (KBr, cm−1): 1607, 1735. 1H NMR (CDCl3): δ=7.28–7.84 (m, 5H), 8.39 (s, 1H), 9.13 (s,1H); MS (EI): m/z=411(M). Anal. Calcd. for C17H7BrN4O2S: C, 49.65; H, 1.72; N, 13.62; Found: C, 49.76; H, 1.79; N, 13.55.

3-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-6,8-dichloro-2H-chromen-2-one (3c)

Mp 280°C. IR (KBr, cm−1): 1604, 1734. 1H NMR (CDCl3): δ=7.24–7.88 (m, 4H), 8.33 (s, 1H), 9.14 (s,1H); MS (EI): m/z=401(M). Anal. Calcd. for. C17H6Cl2N4O2S: C, 50.89; H, 1.51; N, 13.96; Found: C, 50.84; H, 1.61; N, 13.82.

3-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-6,8-dibromo-2H-chromen-2-one (3d)

Mp 268–269°C. IR (KBr, cm−1): 1612, 1738. 1H NMR (CDCl3): δ=7.26–7.91 (m, 4H), 8.35 (s,1H), 9.17 (s, 1H); MS (EI): m/z=490(M). C17H6Br2N4O2S: Anal. Calcd. for C, 41.66; H, 1.23; N, 11.43; Found: C, 41.62; H, 1.31; N, 11.55.

3-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-8-methyl-2H-chromen-2-one (3e)

Mp 225–226°C. IR (KBr, cm−1): 1626, 1724. 1H NMR (CDCl3): δ=2.35 (s, 3H), 7.15–7.92 (m, 5H), 8.24 (s, 1H), 9.1 (s, 1H); MS (EI): m/z=346(M). C18H10N4O2S: Anal. Calcd. for. C, 62.42; H, 2.91; N, 16.18; Found: C, 62.51; H, 2.84; N, 16.32.

3-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-8-chloro-2H-chromen-2-one (3f)

Mp 210°C. IR (KBr, cm−1): 1602,1733. 1H NMR (CDCl3): δ=7.26–7.82 (m, 5H), 8.38 (s, 1H), 9.11 (s, 1H); MS (EI): m/z=366(M). C17H7ClN4O2S: Anal. Calcd. for. C, 55.67; H, 1.92; N, 15.28; Found: C, 55.78; H, 1.81; N, 15.41.

2-([1,2,5]thiadiazolo[3,4-f]quinoxalin-8-yl)-3H-benzo[f]chromen-3-one (3g)

Mp 153–155°C. IR (KBr, cm−1): 1600, 1731. 1H NMR (CDCl3): δ=7.01–7.87 (m, 8H),8.55 (s,1H), 9.24 (s, 1H); MS (EI): m/z=382(M) C21H10N4O2S: Anal. Calcd. for. C, 65.96; H, 2.64; N, 14.65; Found. C, 65.79; H, 2.57; N, 14.78.

Conclusion

In conclusion, cellulose sulfuric acid is found to be an excellent catalytic system for the synthesis of quinoxaline derivatives at RT under solvent-free conditions. This method is found to be more advantageous than the previously reported methods. This catalyst could be directly reused at least three additional times. We claim that cellulose sulfuric acid is a stable and green catalyst.

Acknowledgement

One of the authors B.S.K is grateful to Council of Scientific and Industrial Research (CSIR), New Delhi, Republic of India for providing financial support in the form of CSIR-SRF.

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