A Green Protocol for the Synthesis of Quinoxaline Derivatives Catalyzed by Polymer Supported Sulphanilic Acid

Arabian Journal of Chemistry (2013) xxx, xxx–xxx

King Saud University Arabian Journal of Chemistry

www.ksu.edu.sa www.sciencedirect.com

ORIGINAL ARTICLE A green protocol for the synthesis of quinoxaline derivatives catalyzed by polymer supported sulphanilic acid

Umesh P. Tarpada, Bhautik B. Thummar, Dipak K. Raval *

Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar 388 120, Gujarat, India

Received 21 September 2012; accepted 16 November 2013

KEYWORDS Abstract Polymer supported sulphanilic acid was found to be an effective heterogeneous catalyst Quinoxaline; for one pot synthesis of various quinoxaline derivatives from the condensation reaction between Antioxidant activity; 1,2-diamines and 1,2-dicarbonyl compounds in ethanol. Synthesis was attempted under reﬂux as well Heterogeneous catalyst; as at room temperature using ethanol as the solvent to afford excellent yields. Heterogeneity of the Phenylenediamine; catalyst allowed its recycling for ﬁve times with almost retention in catalytic activity. Prepared quin- 1,2-Diarylketone oxaline derivatives were also tested for their antioxidant activity by the FRAP assay method. ª 2013 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction levomycin and hinomycin which inhibit the growth of Gram- positive bacteria and are active against various transplantable Quinoxaline derivatives are of significant interest as they are tumors (Dell et al., 1975; Bailly et al., 1999). noteworthy intermediates for the manufacturing of pharma- Quinoxalines are very important compounds due to their ceuticals and advanced materials (Sato, 1996; Matsuoka wide spectrum of biological activities such as anticancer et al., 1992). A number of nitrogen-containing heterocycles (Lindsley et al., 2005), antibacterial (Seitz et al., 2002), and show antimicrobial activity and have been synthesized for activity as kinase inhibitors (He et al., 2003). They are well medical use. Among various classes of heterocyclic units, quin- known for their application in rigid subunits in macrocyclic oxaline ring has frequently been used as a component of vari- receptors (Mizuno et al., 2002), electroluminescent materials ous antibiotic molecules. The most striking examples are (Justin Thomas et al., 2005), organic semiconductors (O’Brien et al., 1996) and DNA cleaving agents (Hegedus et al., 2003). Considering the significant applications in the fields of medic- * Corresponding author. Tel.: +91 02692 226856x211; fax: +91 inal, industrial and synthetic organic chemistry, there has been 02692 236475. tremendous interest in developing efficient methods for the E-mail addresses: [email protected], [email protected] synthesis of quinoxalines. (D.K. Raval). Improved methods have been reported by using different Peer review under responsibility of King Saud University. catalysts such as Pd(OAc)2 (Robinson and Taylor, 2005), MnO2 (Raw et al., 2003), ceric ammonium nitrate (More et al., 2006), manganese octahedral molecular sieves Production and hosting by Elsevier (Sithambaram et al., 2008), task-specific ionic liquid

Please cite this article in press as: Tarpada, U.P. et al., A green protocol for the synthesis of quinoxaline derivatives catalyzed by polymer supported sulphanilic acid. Arabian Journal of Chemistry (2013), http://dx.doi.org/10.1016/j.arabjc.2013.11.021 2 U.P. Tarpada et al.

(Dong et al., 2008) and bismuth(III) (Yadav et al., 2008). A were monitored by TLC using an aluminum sheet precoated number of synthetic strategies have been developed for the with silica gel 60 F254 (Merck). preparation of substituted quinoxalines. Although great success has been obtained, many of these methodologies suffer 2.3. General procedure for the modification of Epoxy novolac one or more drawbacks such as drastic reaction conditions, low phenolformaldehyde using sulphanilic acid (ENPFSA) yields, tedious work-up, use of toxic metal salts as catalyst, long reaction times and relatively expensive reagents (More et al., ENPFSA was prepared by modification of Epoxy novolac 2006; Zhao et al., 2004; Bhosale et al., 2005; Heravi et al., phenol formaldehyde resin by sulphanilic acid as reported ear- 2007; Raw et al., 2004; Antoniotti and Dunãch, 2002; Woo lier (Tarpada et al., 2012). et al., 2002; Mizuno et al., 2002; Crossley and Johnston, 2002). The most common methods involve condensation of 2.4. General procedure for the synthesis of quinoxaline 3a an aryl-1,2-diamine with a 1,2-dicarbonyl compound in reflux- ing ethanol or acetic acid for 2–12 h typically giving yields of To a mixture of o-phenylenediamine (1 mmol) and benzil 34–70%. (1 mmol) in ethanol (5 mL), 5% w/w ENPFSA with respect The search for a better alternative catalytic method is being to benzil was added. The mixture was stirred at room temper- actively pursued in our laboratory (Avalani et al., 2012, 2013; ature. The progress of the reaction was monitored by TLC Dadhania et al., 2011, 2012a,b; Patel et al., 2013a,b; Satasia using an aluminum sheet precoated with silica gel 60 F et al., 2013; Tarpada et al., 2012). In the present article, we 254 (Merck). After completion of the reaction, ethyl acetate was have successfully attempted one-pot synthesis of quinoxaline added to the solidified mixture and the insoluble catalyst was derivatives using polymer supported sulphanilic acid from separated by filtration. The filtrate was dried over anhydrous o-phenylenediamines and 1,2-diaryl ketones under mild condi- Na SO . The solvent was evaporated with care and the pure tions. The novel green protocol also tolerated a wide range of 2 4 product was obtained. The product was characterized by FT- functional groups in the building blocks (See Scheme 1). IR, 1H NMR, 13C NMR and GC–MS analysis. The recovered catalyst was washed with ethanol, chloroform, diethyl ether 2. Experimental and subsequently dried at 80 C to recycle in the subsequent model reaction. A variety of substituted 1,2-phenylenediam- 2.1. Chemicals and reagents ines were condensed with 1,2-diaryl ketones to prepare vari- ously substituted quinoxalines (Table 2). All chemicals used were of laboratory reagent grade and used without further purification. Phenol, formaldehyde and Epi- 2.5. Procedure for antioxidant activity chlorohydrin, TPTZ(2,4,6-tripyridyl-s-triazine), Ferric chloride and ascorbic acid were obtained from S.D. Fine Chem. Pvt. Ltd., Mumbai, India. o-Phenylenediamines, sodium FRAP assay was employed to measure total antioxidant hydroxide and sulphanilic acid were obtained from Samir Tech capacity of the compounds. It measures reduction power of Chem. Pvt. Ltd., Vadodara, India. Various 1,2-diketones were the compounds, converting ferric tripyridyl triazine (Fe(III)– used as received from Merck, Mumbai, India. All the solvents TPTZ) complex into a blue colored ferrous tripyridyl triazine were purchased from Sisco Chem. Pvt. Ltd., Mumbai, India. (Fe(II)–TPTZ) complex at low pH, measurable at 593 nm (Benzie and Strain, 1996). 2.2. Analytical methods Fe(II)–TPTZ(2,4,6-tripyridyl-s-triazine) reagent was prepared by mixing a 10.0 mL TPTZ solution, 10 mL FeCl36H2O Melting points were determined by the open capillary method solution and 100 mL acetate buffer at pH 3.6. A mixture of and are uncorrected. 1H NMR and 13C NMR spectra were re- 400.0 lL sample solution and 3 mL of Fe(II)TPTZ reagent corded as solutions in DMSO-d6 on a Bruker Avance 400 spec- was incubated at 37 C for 15 min. The absorbance of the col- trometer operating at 400 MHz for 1H NMR, and 100 MHz ored complex Fe(II)TPTZ was measured at 593 nm using for 13C NMR. Chemical shifts (d) are expressed in parts per ascorbic acid as the standard. The results were expressed as million (ppm) and referenced to the residual protic solvent. ascorbic equivalent (mmol/100 g compound). FT-IR spectra were recorded on ABB Bomem Inc. FT-IR 4 Ascorbic acid taken ¼ 3:99 10 mm; 3000 spectrophotometer and are expressed in wave numbers (cm1). The mass spectra (ESI–MS) were recorded on Shima- Sample taken ¼ 0:04 mg dzu LCMS-2010 spectrometer. Carbon, Hydrogen and Nitro- gen were estimated on a PerkinElmer 2400 Series II CHNS/O Ascorbic acid concentrationðmmol=100g of sampleÞ Elemental Analyzer. Optical density values were recorded on OD at 593nm of test sample standardðmmÞ ¼ 100 Shimadzu UV–VIS spectrophotometer 160A. All the reactions OD at 593nm of standard sampleðmgÞ

Scheme 1 General synthetic pathway for the synthesis of quinoxaline derivatives.

2.6. Characterization of selected compounds of ENPFSA (Table 1, entries 8–13). It was observed that 5% w/w amount of catalyst was enough to complete the reaction 2.6.1. 2,3-Di (furan-2-yl)-6-nitroquinoxaline 3n in a moderate time with high yields. Higher amounts of the IR (KBr): 1566,1520, 1474, 1342, 1011, 910, 887 cm1; 1H catalyst did not increase the yield noticeably. Thus, it was con- cluded that the condensation reaction carried out in the pres- NMR (DMSO-d6, d ppm): 8.77 (d, 1H, J = 2.4 Hz, Ar–H), 8.464 (dd, 1H, J = 2.8 Hz, J = 9.2 Hz, Ar–H), 8.23 (d, 1H, ence of 5% w/w ENPFSA at room temperature showed the J = 9.2 Hz, Ar–H), 7.97 (dd, 2H, J = 0.8 Hz, J = 6.4 Hz, highest conversion. This was chosen as the optimized condi- 13 tion for performing other reactions. Ar–H), 6.89–6.75 (m, 4H, Ar–H); C NMR (DMSO-d6, d ppm):150.17, 150.07, 148.01, 146.78, 146.24, 146.00, 144.54, 144.00, 142.84, 138.91, 130.89, 130.76, 124.93, 124.22, 113.04, 3.2. Effect of different catalysts 112.82; ESI-MS: m/z 308.10 (M + H)+; Anal. Calcd.% for C16H9N3O4: C, 62.54; H, 2.95; N, 13.68, O, 20.83; % Found: Model reaction was carried out by using different catalysts C, 62.63; H, 2.35; N, 20.94. such as HCl, CH3COOH, H2SO4, ZnCl2, CoCl2, NiCl2 and PEG-600. It was found that by using HCl, CH3COOH and 2.6.2. 6-Chloro-2, 3-dip-tolylquinoxaline 3q H2SO4 as the catalyst, reaction was completed in 85 min with IR (KBr): 1605,1466, 1335, 1242, 1180, 1065, 980, 818, 725, 80% yield under reflux and in 100 min with 75% yield at room 1 1 temperature (Table 1, entries 1–3). 602 cm ; H NMR (DMSO-d6, d ppm): 8.19–8.13 (m, 2H, Ar–H), 7.86 (dd, 1H, J = 2.4 Hz, J = 8.8 Hz, Ar–H), 7.37 By using ZnCl2, CoCl2, NiCl2 as the catalyst, reaction got (d, 4H, J = 8 Hz, Ar–H), 7.177 (d, 4H, J = 7.6 Hz, Ar–H), completed in 90 min with 80% yield under reflux and in 13 110 min with 75% yield at room temperature (Table 1, entry 2.329 (s, 6H); C NMR (DMSO-d6, d ppm): 154.42, 153.84, 141.17, 139.51, 139.13, 139.03, 136.18, 136.12, 134.85, 131.27, 4–6). The reaction was completed in a shorter time with high 131.12, 130.10, 129.65, 129.42, 129.23, 129.15, 128.92, 127.96, yields by using acid catalyst as compared to metal chloride as + catalysts. Using PEG-600 as the catalyst, reaction was com- 127.80; ESI-MS: m/z 345.2 (M + H) ; Anal. Calcd.% for C22- pleted in 80 min with 85% yield under reflux and in 85 min H17ClN2: C, 76.63; H, 4.97; N, 8.12; % Found: C, 76.93; H, 5.31; N, 8.25. with 80% yields at room temperature (Table 1, entry 7). The model reaction was performed by using 5% polymer supported sulphanilic acid (ENPFSA) as the catalyst. Reac- 3. Result and discussion tion was completed in 35 min with 90% yield under reflux and in 40 min with 88% yield at room temperature (Table 1, 3.1. Optimization of reaction conditions entry 12). By using this optimized conditions, various quinoxaline The condensation reaction of benzene-1,2-diamine with benzil derivatives 3b–t were synthesized in a shorter time as well as using ethanol as the solvent was employed as the model reac- in high yields. It was observed that diketone having the phenyl tion to screen the suitable reaction conditions (Table 1). ring as the substituents underwent the conversion smoothly in Among different catalysts and ENPFSA (Table 1, entries 1– a short time as compared to diketone having furyl and thenyl 12), 5% w/w ENPFSA was found to be the best suited for ring as the substituents. The diamine component carrying the the reaction. The reaction was studied at the reflux tempera- electron withdrawing group (Table 2, entries 11–15) underwent ture as well as at room temperature. Increasing the reaction the reaction in a shorter time with high yields as compared to temperature to reflux had only a marginal effect on % yield diamines carrying the electron donating group (Table 2, entries (Table 1). Reaction was also optimized by varying the amount 6–10 and 16–20).

Table 1 Effect of different catalysts on the condensation of benzil and benzene-1,2-diamine in ethanol as the solvent at room temperature and at reﬂux. Entry Catalyst At room temperature Reﬂux Timea (min) Yieldsb (%) Timea (min) Yieldsb (%) 1 1 mmol% HCl 100 75 85 80

2 1 mmol% CH3COOH 100 75 85 80 3 1 mmol% H2SO4 100 75 85 80 4 1 mmol% ZnCl2 110 75 90 80 5 1 mmol% CoCl2 110 75 90 80 6 1 mmol% NiCl2 110 75 90 80 7 1 mmol% PEG-600 85 80 80 85 8 1% ENPFSA 45 65 40 70 9 2% ENPFSA 45 70 40 72 10 3% ENPFSA 45 73 40 75 11 4% ENPFSA 45 75 40 80 12 5% ENPFSA 40 88 35 90 13 6% ENPFSA 50 83 40 85 a Reaction was monitored by TLC. b Isolated yields.

Table 2 Synthesis of quinoxaline 3a–t by using ENPFSA as heterogeneous catalyst in ethanol at room temperature. a b Entry Product RR1 Time (min.) Yield (%) Melting point (C) Observed Reported

13aHC6H5 40 88 126 126–127 More et al. (2006) 23bHp-CH3C6H4 45 85 147 147–148 Guo et al. (2009) 3 3c H Phenanthrene-9,10-dionec 45 85 225 224.8–225.7 Kaupp and Naimi-Jamal (2002) 4 3d H 2-Furyl 50 80 132 131 More et al. (2005) 5 3e H 2-Thenyl 50 82 140 –

63fCH3 C6H5 45 84 116 116–117 Kaupp and Naimi-Jamal (2002) 73gCH3 p-CH3C6H4 48 80 137 137 Kaupp and Naimi-Jamal (2002) c 83hCH3 Phenanthrene-9,10-dione 48 84 209 208–210 Kaupp and Naimi-Jamal (2002) 93iCH3 2-Furyl 52 80 118 117–119 Akkilagunta et al. (2010) 10 3j CH3 2-thenyl 52 80 110 – 11 3k NO2 C6H5 38 88 192 192–193 Kaupp and Naimi-Jamal (2002) 12 3l NO2 p-CH3C6H4 41 86 168 168–169 Guo et al. (2009) c 13 3m NO2 Phenanthrene-9,10-dione 41 86 245 – 14 3n NO2 2-Furyl 45 85 165 164–166 Guo et al. (2009) 15 3o NO2 2-Thenyl 45 85 220 – 16 3p Cl C6H5 42 84 115 115–116 Kaupp and Naimi-Jamal (2002) 17 3q Cl p-CH3C6H4 45 84 170 169–171 Akkilagunta et al. (2010) 18 3r Cl Phenanthrene-9,10-dionec 45 85 225 – 19 3s Cl 2-Furyl 48 82 133 133–135 Akkilagunta et al. (2010) 20 3t Cl 2-Thenyl 48 82 190 – a Reaction were monitored by TLC. b Isolated yields. c Name of diketone employed for the synthesis.

3.3. Mechanism for the formation of quinoxaline 3.4. Recyclability of catalyst

The formation of quinoxaline derivatives is outlined in Recyclability of the catalyst was studied by using the ENPFSA Scheme 2. 1,2-diketone stabilized in the interlayer of ENPFSA recovered from the previous batch in the model reaction. The via interaction with H+ by the partial polarization of carbonyl reaction proceeded smoothly yielding 85–88% of the product group reacts readily with o-phenylenediamine. The resultant at room temperature for ﬁve successive runs (Table 3). The amino-1,2-diol undergoes dehydration to give quinoxaline as result indicates that activity of the catalyst was not much the end product. affected upon recycling at least for ﬁve times.

3.5. Antioxidant activity of quinoxalines

Capacity to transfer a single electron i.e., the antioxidant power of all compounds was determined by a FRAP assay. The FRAP values are expressed as an equivalent of standard antioxidant ascorbic acid (mmol/100 g of dried compound). FRAP values indicate that all the compounds have a ferric reducing antioxidant power. The compounds 3k, 3m, 3p, 3r, 3s and 3t (Table 4, entries 11, 13, 16, 18, 19 and 20) showed relatively high antioxidant activity whereas compound 3f (Table 4, entry 6) showed poor antioxidant power. The high antioxidant activity may be due to the presence of the electron

Table 3 Recyclability of catalyst. No. of cycles Reaction timea Yieldb (%) 14088 24088 34086 44086 54085 a Reaction was monitored by TLC. b Scheme 2 Plausible mechanism for the formation of Isolated yields. quinoxaline.

Table 4 Antioxidant activity of synthesized compounds by References FRAP assay method. Akkilagunta, V.K., Reddy, V.P., Kakulapati, R.R., 2010. Aqueous- Entry Compound OD (593 nm) FRAP value (mmol/100 g) phase aerobic oxidation of alcohols by Ru/C in the presence of 1 3a 1.200 242.05 cyclodextrin: one-pot biomimetic approach to quinoxaline synthe- 2 3b 0.548 110.53 sis. Synlett, 2571–2574, doi:10.1055/s-0030-1258775. 3 3c 0.531 107.11 Antoniotti, S., Dunãch, E., 2002. Direct and catalytic synthesis of 4 3d 1.023 206.34 quinoxaline derivatives from epoxides and ene-1,2-diamines. Tet- 5 3e 0.967 195.05 rahedron Lett. 43, 3971–3973. 6 3f 0.482 97.22 Avalani, J.R., Patel, D.S., Raval, D.K., 2012. 1-Methylimidazolium 7 3g 0.542 109.32 trifluoroacetate [Hmim]Tfa: mild and efficient Brønsted acidic ionic 8 3h 1.024 206.55 liquid for Hantzsch reaction under microwave irradiation. J. Chem. 9 3i 1.202 242.45 Sci. 124, 1091–1096. 10 3j 0.987 199.09 Avalani, J.R., Patel, D.S., Raval, D.K., 2013. Saccharomyces cerevi- 11 3k 1.520 306.59 siae catalyzed one pot synthesis of isoindolo[2,1-a]quinazoline 12 3l 0.543 109.53 performed under ultrasonication. J. Mol. Catal. B Enzym. 90, 70– 13 3m 1.890 381.23 75. 14 3n 0.545 109.93 Bailly, C., Echepare, S., Gago, F., Waring, M.J., 1999. Recognition 15 3o 1.072 216.23 elements that determine affinity and sequence-specific binding to 16 3p 1.680 338.87 DNA of 2QN, a biosynthetic bis-quinoline analogue of echinomy- 17 3q 0.502 101.26 cin. Anti-Cancer Drug Des. 14, 291–303. 18 3r 2.203 444.37 Benzie, I.F.F., Strain, J.J., 1996. The Ferric Reducing Ability of 19 3s 1.892 381.63 Plasma (FRAP) as a Measure of ‘‘Antioxidant Power’’: the FRAP 20 3t 1.558 314.26 Assay. Anal. Biochem. 239, 70–76. Bhosale, R.S., Sarda, S.R., Ardhapure, S.S., Jadhav, W.N., Bhusare, S.R., Pawar, R.P., 2005. An efficient protocol for the synthesis of quinoxaline derivatives at room temperature using molecular iodine as the catalyst. Tetrahedron Lett. 46, 7183–7186. withdrawing substituent in compounds or the presence of the Crossley, M.J., Johnston, L.A., 2002. Laterally-extended porphyrin furyl or thiophene ring. systems incorporating a switchable unit. Chem. Commun. 10, 1122–1123. Dadhania, A.N., Patel, V.K., Raval, D.K., 2011. A convenient and 4. Conclusion efficient protocol for the one pot synthesis of 3,4-dihydropyrimidin- 2-(1H)-ones catalyzed by ionic liquids under ultrasound irradiation. J. Brazilian Chem. Soc. 22, 511–516. We have reported a green and efficient protocol for one-pot Dadhania, A.N., Patel, V.K., Raval, D.K., 2012a. Catalyst-free synthesis of quinoxaline derivatives from readily available sonochemical synthesis of 1,8-dioxo-octahydroxanthene derivatives o-phenylenediamines and 1,2-diarylketones using a polymer in carboxy functionalized ionic liquid. C. R. Chim. 15, 378–383. supported catalyst. The conditions are mild and a wide range Dadhania, A.N., Patel, V.K., Raval, D.K., 2012b. A facile approach of functional groups can be tolerated in the building blocks for the synthesis of 3,4-dihydropyrimidin-2-(1H)-ones using a for the synthesized quinoxalines. ENPFSA as catalyst offered microwave promoted Biginelli protocol in ionic liquid. J. Chem. advantages including simplicity of operation, easy workup, Sci. 124, 921–926. time savvy and recyclability to give excellent purity and high Dell, A., Williams, D.H., Morris, H.R., Smith, G.A., Feeney, J., Roberts, G.C.K., 1975. Structure revision of the antibiotic echino- yields of products. Synthesized compounds showed good to mycin. J. Am. Chem. Soc. 97, 2497–2502. moderate antioxidant activity by FRAP assay method. Dong, F., Kai, G., Zhenghao, F., Xinli, Z., Zuliang, L., 2008. A practical and efficient synthesis of quinoxaline derivatives catalyzed by task-specific ionic liquid. Catal. Commun. 9, 317–320. Acknowledgements Guo, W.X., Jin, H.L., Chen, J.X., Ding, F.C., Wu, H.Y., 2009. An efficient catalyst-free protocol for the synthesis of quinoxaline derivatives under ultrasound irradiation. J. Braz. Chem. Soc. 20, Authors thank the Head, Department of Chemistry, Sardar 1674–1679. Patel University for providing research facilities. DKR grate- He, W., Myers, M.R., Hanney, B., Spada, A.P., Bilder, G., Galzcinski, fully acknowledges Sardar Patel University for allocation of H., Amin, D., Needle, S., Page, K., Jayyosi, Z., Perrone, M.H., partial research funding in terms of seed grant-2011. UPT is 2003. Potent quinoxaline-based inhibitors of PDGF receptor grateful to UGC, New Delhi for providing senior research tyrosine kinase activity. Part 2: the synthesis and biological fellowship in science for meritorious students for the academic activities of RPR127963 an orally bioavailable inhibitor. Bioorg. years 2012–2015. Med. Chem. Lett. 13, 3097–3100. Hegedus, L.S., Greenberg, M.M., Wendling, J.J., Bullock, J.P., 2003. Synthesis of 5,12-Dioxocyclam Nickel (II) Complexes Having Quinoxaline Substituents at the 6 and 13 Positions as Potential DNA Bis-Intercalating and Cleaving Agents. J. Org. Chem. 68, Appendix A. Supplementary data 4179–4188. Heravi, M.M., Taheri, S., Bakhtiari, K., Oskooie, H.A., 2007. On Supplementary data associated with this article can be found, water: a practical and efficient synthesis of quinoxaline derivatives catalyzed by CuSO 5H O. Catal. Commun. 8, 211–214. in the online version, at http://dx.doi.org/10.1016/j.arabjc.2013 4 2 .11.021.

Justin Thomas, K.R., Velusamy, M., Lin, J.T., Chuen, C.-H., Raw, S.A., Wilfred, C.D., Taylor, R.J.K., 2004. Tandem oxidation Tao, Y.-T., 2005. Chromophore-labeled quinoxaline derivatives processes for the preparation of nitrogen-containing heteroaro- as efficient electroluminescent materials. Chem. Mater. 17, matic and heterocyclic compounds. Org. Biomol. Chem. 2, 788– 1860–1866. 796. Kaupp, G., Naimi-Jamal, M.R., 2002. Quantitative cascade conden- Robinson, R.S., Taylor, R.J.K., 2005. Quinoxaline synthesis from sations between o-phenylenediamines and 1,2-dicarbonyl com- a-hydroxy ketones via a tandem oxidation process using catalysed pounds without production of wastes. Eur. J. Org. Chem. 2002, aerobic oxidation. Synlett 6, 1003–1005. 1368–1373. Satasia, S.P., Kalaria, P.N., Raval, D.K., 2013. Acidic ionic liquid Lindsley, C.W., Zhao, Z., Leister, W.H., Robinson, R.G., Barnett, immobilized on cellulose: an efficient and recyclable heterogeneous S.F., Defeo-Jones, D., Jones, R.E., Hartman, G.D., Huff, J.R., catalyst for the solvent-free synthesis of hydroxylated trisubstituted Huber, H.E., Duggan, M.E., 2005. Allosteric Akt (PKB) inhibitors: pyridines. RSC Adv. 3, 3184–3188. discovery and SAR of isozyme selective inhibitors. Bioorg. Med. Sato, N. 1996. 6.03 – Pyrazines and their Benzo Derivatives. In: Chem. Lett. 15, 761–764. EDITORS-IN CHIEF: Alan, R.K., Charles, W.R., Eric F.V. Matsuoka, M., Iwamoto, A., Furukawa, N., Kitao, T., 1992. SCRIVENA2 – EDITORS-IN-CHIEF: Alan R. Katritzky, Syntheses of polycyclic-1,4-dithiines and related heterocycles. C.W.R., Eric, F.V.S. (eds.) Comprehensive Heterocyclic Chemistry J. Heterocycl. Chem. 29, 439–443. II. Oxford: Pergamon, 233–278. Mizuno, T., Wei, W.-H., Eller, L.R., Sessler, J.L., 2002. Phenanthro- Seitz, L.E., Suling, W.J., Reynolds, R.C., 2002. Synthesis and line complexes bearing fused dipyrrolylquinoxaline anion recogni- antimycobacterial activity of pyrazine and quinoxaline derivatives. tion sites: efficient fluoride anion receptors. J. Am. Chem. Soc. 124, J. Med. Chem. 45, 5604–5606. 1134–1135. Sithambaram, S., Ding, Y., Li, W., Shen, X., Gaenzler, F., Suib, More, S.V., Sastry, M.N.V., Wang, C.-C., Yao, C.-F., 2005. Molecular S.L., 2008. Manganese octahedral molecular sieves catalyzed iodine: a powerful catalyst for the easy and efficient synthesis of tandem process for synthesis of quinoxalines. Green Chem. quinoxalines. Tetrahedron Lett. 46, 6345–6348. 10, 1029–1032. More, S.V., Sastry, M.N.V., Yao, C.-F., 2006. Cerium(iv) ammonium Tarpada, U.P., Thummar, B.B., Raval, D.K., 2012. Polymer sup- nitrate (CAN) as a catalyst in tap water: A simple, proficient and ported sulfanilic acid: a novel green heterogeneous catalyst for green approach for the synthesis of quinoxalines. Green Chem. 8, synthesis of benzimidazole derivatives. J. Saudi. Chem. Soc., 91–95. doi:10.1016/j.jscs.2012.07.014. O’brien, D., Weaver, M.S., Lidzey, D.G., Bradley, D.D.C., 1996. Use Woo, G.H.C., Snyder, J.K., Wan, Z.-K. 2002. Chapter 6.2 Six- of poly(phenyl quinoxaline) as an electron transport material in membered ring systems: Diazines and benzo derivatives. In: polymer light-emitting diodes. Appl. Phys. Lett. 69, 881–883. Gordon, W.G., Thomas, L.G. (eds.), Progress in Heterocyclic Patel, D.S., Avalani, J.R., Raval, D.K., 2013a. One-pot solvent-free Chemistry. Elsevier, 14, 279–309. rapid and green synthesis of 3,4-dihydropyrano[c]chromenes using Yadav, J.S., Subba Reddy, B.V., Premalatha, K., Shankar, K.S., 2008. grindstone chemistry. J. Saudi Chem. Soc., http://dx.doi.org/ Bismuth(III)-catalyzed rapid synthesis of 2,3-disubstituted quinox- 10.1016/j.jscs.2012.12.008. alines in water. Synthesis 23, 3787–3792. Patel, J.P., Avalani, J.R., Raval, D.K., 2013b. Polymer supported Zhao, Z., Wisnoski, D.D., Wolkenberg, S.E., Leister, W.H., Wang, Y., sulphanilic acid: A highly efficient and recyclable green heteroge- Lindsley, C.W., 2004. General microwave-assisted protocols for the neous catalyst for the construction of 4,5-dihydropyrano[3,2-c] expedient synthesis of quinoxalines and heterocyclic pyrazines. chromenes under solvent-free conditions. J. Chem. Sci. 125, 531– Tetrahedron Lett. 45, 4873–4876. 536. Raw, S.A., Wilfred, C.D., Taylor, R.J.K., 2003. Preparation of quinoxalines, dihydropyrazines, pyrazines and piperazines using tandem oxidation processes. Chem. Commun. 18, 2286–2287.