1 Introduction

On the ground of environmental concerns, chemists and researchers are switching their interest towards synthetic processes which incorporate the environmentally benign reagents for the synthesis of highly privileged scaffolds and this has emerged as a phenomenally recommended platform [1,2,3]. Taking into account the principle of green chemistry, avoiding hazardous reaction conditions by utilization of renewable feedstocks and supramolecular chemistry has acquired prodigious significance [4,5,6]. Chemical reactions in the presence of a supramolecular catalyst which is derived from biomass, boost the sustainability of the procedure [7,8,9]. Within this context, cyclodextrins (CDs), cyclic oligosaccharides of D(+)-glucopyranosyl units which are associated by α-1,4-glycosidic linkage, have noteworthy engrossment with an exclusive characteristic of hydrophilic exterior and a hydrophobic central void. Cyclodextrins, generally obtained by the enzymatic degradation of starch have characteristic cylindrical shape with a narrow and a broad end. One primary hydroxyl group is present at the narrower end where as secondary hydroxyl groups are present at the second and third carbon of the broader end of cyclodextrin [10,11,12]. On the basis of the number of D(+)-glucopyranosyl units, CDs are generally classified into 3 categories namely α-, β and γ-CDs having 6, 7 and 8 D(+)-glucopyranosyl units, respectively [13,14,15,16]. The diameters of hydrophobic cavities for different CDs (α-, β and γ-CDs) are in the order of 0.47–0.56, 6.0–6.5 and 7.5–8.3 nm, respectively and the heights of all CDs are around 0.78 nm [13]. The structure of cyclodextrins facilitates them to form inclusion complexes with numerous substrates via weak interactions like non-covalent bonding, H-bonding and vander waal forces of attraction and by ensnaring the substrate into their hydrophobic cavities [9, 16,17,18]. Among the three, β-cyclodextrin (β-CD) is the most frequently used CD. These attributes of CDs invigorated us to carry out our reaction in presence of β-cyclodextrin.

Now-a-days, atom and step economic approaches are utilized under the heading of multicomponent reactions (MCRs) for the straightforward access of diverse classes of compounds and this has emerged as a key tool for ecofriendly and sustainable protocols in organic synthesis [19,20,21,22].

Benzo[a]pyrano[2,3-c]phenazine, a nitrogen and oxygen containing heterocyclic compound, reveals tremendous biological and pharmaceutical significance. It consists of two characteristic units of important classes of heterocyclic compounds in which one is nitrogen-containing phenazine unit and the other one is oxygen containing pyran (Fig. 1). Phenazines form the core structure of various natural and synthetic products [23] and exhibit diverse biological activities as antiplatelet [24], antimalarial [25], fungicidal [26], antitumor [27], trypanocidal [28] and anti-inflammatory activities [29]. In addition, they are also used as pesticides and dyestuffs [30].

Fig. 1
figure 1

Structure of Benzo[a]pyrano[2,3-c]phenazine showing Phenazine and Pyran unit

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Similarly, Pyrans are also present as a key motif in various natural products and pharmaceuticals as polyether antibiotics, alkaloids and carbohydrates [31, 32]. Compounds with pyran scaffold shows astonishing biological importances such as antitumor, antifungal, antioxidant, antileishmanial, anticoagulant, anticonvulsant and antimicrobial activities. In addition, they are extensively used as potential biodegradable agrochemicals, pigments and cosmetics [33,34,35,36] (Fig. 2).

Fig. 2
figure 2

Some biologically active derivatives of Phenazines and Pyran

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Even though, various synthetic pathways for Benzo[a]pyrano[2,3-c]phenazine and its derivatives have been reported [30, 37,38,39,40,41,42,43,44,45,46,47] but some of them are endured with some downsides. In view of the vast biological significance of Benzo[a]pyrano[2,3-c]phenazine and our ongoing interest in the development of new green synthetic methodologies for heterocyclic compounds [48,49,50,51,52,53], we sought to develop a straightforward and facile domino synthetic protocol for Benzo[a]pyrano[2,3-c]phenazines by using 2-hydroxynaphthalene-1,4-dione, o-phenylenediamines, aromatic aldehydes and malononitrile as reactants in presence of β-cyclodextrin in EtOH:H2O (1:1) solvent at 70 °C (Scheme 1).

Scheme 1
scheme 1

Synthesis of Benzo[a]pyrano[2,3-c]phenazines

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2 Experimental

2.1 General Information

Reagents were obtained from commercial suppliers and used without further purification unless otherwise specified by a reference. All reactions were performed using oven-dried glass wares. Organic solutions were concentrated using a Buchi rotary evaporator. TLC was performed using silica gel GF254 (Merck) plates. Melting points were determined by open glass capillary method and are uncorrected. IR spectra in KBr were recorded on a Perkin-Elmer 993 IR spectrophotometer, 1HNMR and 13C NMR spectra were recorded on a Bruker AVII 400 and 100 MHz spectrometer in DMSO-d6 using TMS as internal reference with chemical shift value being reported in ppm. All coupling constants (J) have been reported in Hertz (Hz).

2.2 General Method for the Synthesis of Benzo[a]pyrano[2,3-c]phenazine Derivatives (5a-p)

To a homogeneous solution of β-cyclodextrin (20 mol%) in 15 ml of ethanol:water (1:1) at 70 °C, 1.0 mmol of 2-hydroxynaphthalene-1,4-dione (1), o-phenylenediamine (2), aromatic aldehyde (3) and malononitrile (4) were added and stirred until the completion of reaction (monitored by TLC) then water (10 ml) was added. Product was precipitated out which was filtered off by using Whatman filter paper. The crude product was purified by column chromatography by using ethyl acetate and hexane as eluent. All the desired products were known and were characterized by the comparison of their spectra and melting points with those reported in the literature [37,38,39,40,41,42,43,44,45,46,47].

2.3 Spectral Data of Compounds

2.3.1 3-Amino-1-phenyl-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5a)

Yellow solid, M.P.: 297–299 °C; IR (KBr) ν (cm−1): 3440, 3315, 3171, 2183, 1652, 1626, 1595, 1544, 1491, 1477, 1400, 1381, 1353, 1322, 1263, 1165, 1121, 1048, 1021, 759, 731, 704; 1H NMR (400 MHz, DMSO-d6) δ: 9.15 (d, 1H, J = 7.6 Hz), 8.40 (d, 1H, J = 8.0 Hz), 8.23–8.20 (m, 1H), 8.10–8.07 (m, 1H), 8.01–7.91 (m, 4H), 7.42–7.38 (m, 4H), 7.22 (t, 2H, J = 7.6 Hz), 7.10–7.06 (m, 1H), 5.43 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 159.6, 146.5, 145.2, 141.2, 140.2, 140.1, 139.5, 130.5, 130.3, 130.1, 129.7, 129.2, 129.0, 128.4, 128.1, 127.3, 126.3, 125.2, 124.4, 122.0, 120.3, 113.6, 58.0, 37.1; MS (ESI) m/z: 400.

2.3.2 3-Amino-1-(4-chloro-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5b)

Yellow solid, M.P.: 286–289 °C; IR (KBr) ν (cm−1): 3449, 3304, 3170, 2181, 1658, 1621, 1590, 1483, 1470, 1400, 1381, 1345, 1322, 1288, 1262, 1160, 1101, 1081, 1049, 1012, 843, 756, 747; 1H NMR (400 MHz, DMSO-d6) δ: 9.29–9.27 (d, 1H, J = 8.76 Hz), 8.49–8.47 (d, 1H, J = 8.6 Hz), 8.33–8.31 (m, 1H), 8.21–8.18 (m, 1H), 8.05–7.94 (m, 4H), 7.47–7.45 (m, 4H), 7.31–7.28 (m, 2H), 5.55 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 159.6, 152.0, 144.1, 140.3, 139.6, 131.1, 130.6, 130.2, 130.1, 130.0, 129.3, 129.1, 128.4, 128.0,125.3, 124.4, 122.0, 120.1, 113.1, 57.3; MS (ESI) m/z: 434.

2.3.3 3-Amino-1-(2-chlorophenyl)-1H-benzo[c]pyrano[2,3-c]phenazine-2-carbonitrile (5c)

Yellow solid, M.P.: 300–302 °C; IR (KBr) ν (cm−1): 3331, 3237, 3144, 2981, 1653, 1581, 1472, 1383, 1271, 1153, 1038, 950, 831, 755; 1H NMR (400 MHz, DMSO-d6) δ: 9.27 (d, 1H, J = 8.0 Hz), 8.48 (d, 1H, J = 8.0 Hz), 8.30–8.27 (m, 1H), 8.04–7.93 (m, 3H), 7.93–7.90 (m, 2H), 7.42–7.40 (m, 1H), 7.34 (s, 2H), 7.23–7.21 (m, 1H), 7.13–7.09 (m, 2H), 6.01 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 170.1, 159.1, 146.3, 142.3, 141.2, 140.3, 140.0, 139.6, 132.0, 130.6, 130.3, 130.1, 130.0, 129.2, 129.1, 129.0, 128.3, 128.0, 127.1, 125.2, 124.5, 122.1, 119.2, 112.7, 56.6, 36.5; MS (ESI) m/z: 434.

2.3.4 3-Amino-1-(2,4-dichlorophenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5d)

Brown solid, M.P.: 305–308 °C; IR (KBr) ν (cm−1): 3471, 3310, 3162, 3063, 2181, 1653, 1620, 1584, 1463, 1400, 1381; 1H NMR (400 MHz, DMSO-d6) δ: 9.17 (d, 1H, J = 8.0 Hz), 8.40 (d, 1H, J = 8.0 Hz), 8.19–8.21 (m, 1H), 7.86–8.02 (m, 5H), 7.51 (s, 1H), 7.38 (s, 2H), 7.18 (d, 1H, J = 8.0 Hz), 7.11 (d, 1H, J = 8.0 Hz), 5.82 (s, 1H); MS (ESI) m/z: 469.

2.3.5 3-Amino-1-(4-bromo-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5e)

Yellow solid, M.P.: 281–283 °C; IR (KBr) ν (cm−1): 3464, 3311, 3171, 2184, 1657, 1621, 1588, 1400, 1381, 1346, 1327, 1289, 1219, 1161, 1101, 1051, 1007, 841, 753, 676; 1H NMR (400 MHz, DMSO-d6) δ: 9.25-9.21 (m, 1H), 8.46–8.44 (m, 1H), 8.30–8.27 (m, 1H), 8.18–8.13 (m, 1H), 8.03–7.91 (m, 4H), 7.44–7.40 (m, 4H), 7.37–7.35 (m, 2H), 5.50 (s, 1H); MS (ESI) m/z: 479.

2.3.6 3-Amino-1-(3-bromophenyl)-1H-benzo[a]pyrano[2,3-c] Phenazine-2-carbonitrile (5f)

Brown solid, M.P.: 266–268 °C; IR (KBr) ν (cm−1): 3481, 3300, 3165, 3057, 2191, 1658, 1622, 1587, 1467, 1381; 1H NMR (400 MHz, DMSO-d6) δ: 9.20–9.24 (m, 1H), 8.41–8.46 (m, 1H), 8.26–8.30 (m, 1H), 8.12–8.15 (m, 1H), 7.93–8.00 (m, 4H), 7.60–7.62 (m, 1H), 7.45–7.48 (m, 2H), 7.39–7.43 (m, 1H), 7.27–7.31 (m, 1H), 7.17–7.21 (m, 1H), 5.49 (s, 1H); MS (ESI) m/z: 479.

2.3.7 3-Amino-1-(4-methoxyphenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5 g)

Yellow solid, M.P.: 268–270 °C; IR (KBr) ν (cm−1): 3428, 3311, 3191, 3041, 2190, 1661, 1592, 1503, 1381; 1H NMR (400 MHz, DMSO-d6) δ: 9.25 (d, 1H, J = 8.0 Hz), 8.44 (d, 1H, J = 8.0 Hz), 8.28–8.30 (m, 1H), 8.19–8.21 (m, 1H), 7.93–7.98 (m, 4H), 7.31 (d, 2H, J = 8.0 Hz), 7.17–7.19 (m, 2H), 6.75 (d, 2H, J = 8.0 Hz), 5.48 (s, 1H), 3.60 (s, 3H); MS (ESI) m/z: 430.

2.3.8 3-Amino-1-(2-methoxy-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5 h)

Yellow solid, M.P.: 268–270 °C; IR (KBr) ν (cm−1): 3309, 3169, 3051, 2827, 2181, 1652, 1621, 1591, 1484, 1471, 1452, 1395, 1381, 1347, 1327, 1287, 1247, 1161, 1100, 1048, 1021, 829, 751; 1H NMR (400 MHz, DMSO-d6) δ: 9.25–9.23 (m, 1H), 8.47–8.45 (m, 1H), 8.28–8.24 (m, 1H), 8.05–7.88 (m, 5H), 7.20 (s, 2H), 7.11-7.04 (m, 2H), 6.94 (d, 1H, J = 7.6 Hz), 6.75–6.71 (m, 1H), 5.84 (s, 1H), 3.85 (s, 3H); MS (ESI) m/z: 430.

2.3.9 3-Amino-1-(3-methoxyphenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5i)

Yellow solid, M.P.: 236–241 °C; IR (KBr) ν (cm−1): 3416, 3336, 3211, 2189, 1661, 1591, 1487, 1381; 1H NMR (400 MHz, DMSO-d6) δ: 9.20 (d, 1H, J = 8.0 Hz), 8.41 (d, 1H, J = 8.0 Hz), 8.23–8.26 (m, 1H), 8.13–8.16 (m, 1H), 7.97 (t, 2H, J = 8.0 Hz), 7.91–7.92 (m, 2H), 7.39 (s, 2H), 7.11 (t, 1H, J = 8.0 Hz), 7.00 (s, 1H), 6.90 (d, 1H, J = 8.0 Hz), 6.65 (d, 1H, J = 8.0 Hz), 5.46 (s, 1H), 3.65 (s, 3H); MS (ESI) m/z: 430.

2.3.10 3-Amino-1-p-tolyl-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5j)

Yellow solid, M.P.: 291–293 °C; IR (KBr) ν (cm−1): 3439, 3307, 3171, 2183, 1657, 1621, 1591, 1492, 1471, 1394, 1380, 1346, 1322, 1286, 1261, 1219, 1157, 1101, 1051, 1018, 826, 753, 741; 1H NMR (400 MHz, DMSO-d6) δ: 9.22 (d, 1H, J = 8.0 Hz), 8.43–8.42 (m, 1H), 8.27–8.24 (m, 1H), 8.16–8.13 (m, 1H), 8.01–7.90 (m, 4H), 7.32–7.26 (m, 4H), 7.01 (d, 2H, J = 8.0 Hz), 5.45 (s, 1H), 2.13 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 168.0, 164.1, 159.5, 150.1, 146.2, 141.3, 140.0, 135.3, 130.6, 129.9, 129.3, 129.0, 128.7, 127.4, 125.5, 123.4, 122.0, 118.1, 58.1, 36.9, 20.3; MS (ESI) m/z: 414.

2.3.11 3-Amino-1-(4-nitro-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5 k)

Yellow solid, M.P.: 280–282 °C; IR (KBr) ν (cm−1): 3327, 3311, 3249, 3195, 2194, 1671, 1588, 1510, 1471, 1399, 1381, 1341, 1289, 1261, 1215, 1162, 1103, 1049, 1021, 823, 768, 741; 1H NMR (400 MHz, DMSO-d6) δ: 9.26 (d, 1H, J = 7.6 Hz), 8.48 (d, 1H, J = 8.0 Hz), 8.30-8.28 (m, 1H), 8.15–8.13 (m, 1H), 8.10 (d, 2H, J = 8.4 Hz), 8.05–7.91 (m, 4H), 7.70 (d, 2H, J = 8.8 Hz), 7.54 (s, 2H), 5.66 (s, 1H); MS (ESI) m/z: 445.

2.3.12 3-Amino-1-(3-nitro-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5 l)

Yellow solid, M.P.: 276–278 °C; IR (KBr) ν (cm−1): 3421, 3333, 3194, 2187, 1661, 1625, 1591, 1521, 1492, 1471, 1397, 1384, 1341, 1288, 1261, 1161, 1102, 1049, 1022, 808, 758, 726, 692; 1H NMR (400 MHz, DMSO-d6) δ: 9.11 (d, 1H, J = 7.6 Hz), 8.40 (d, 1H, J = 8.0 Hz), 8.28 (s, 1H), 8.20–8.12 (m, 1H), 8.05–8.03 (m, 1H), 7.98–7.95 (m, 2H), 7.90–7.86 (m, 4H), 7.53–7.51 (m, 3H), 5.57 (s, 1H); MS (ESI) m/z: 445.

2.3.13 3-Amino-11,12-dimethyl-1-phenyl-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5 m)

Yellow solid, M.P.: 295–297 °C; IR (KBr) ν (cm−1): 3471, 3291, 3174, 3023, 2186, 1659, 1631, 1593, 1491, 1385, 1338, 1291, 1262, 1203, 1162, 1105, 1054, 1023, 997, 861, 762; 1H NMR (400 MHz, DMSO-d6) δ: 9.11 (d, 1H, J = 8.0 Hz), 8.39 (d, 1H, J = 8.0 Hz), 7.97–7.85 (m, 3H), 7.69 (s, 1H), 7.37–7.34 (m, 4H), 7.21 (t, 2H, J = 7.6 Hz), 7.07 (t, 1H, J = 7.6 Hz), 5.41 (s, 1H), 2.42 (s, 6H); MS (ESI) m/z: 428.

2.3.14 3-Amino-11,12-dimethyl-1-(4-nitro-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5n)

Yellow solid, M.P.: 296–298 °C; IR (KBr) ν (cm−1): 3491, 3319, 3163, 2185, 1656, 1629, 1587, 1509, 1469, 1382, 1341, 1294, 1205, 1165, 1105, 1053, 1021, 853, 824, 756, 711; 1H NMR (400 MHz, DMSO-d6) δ: 9.10 (dd, 1H, J = 0.8 Hz, 8.0 Hz), 8.40 (dd, 1H, J = 1.2 Hz, 8.0 Hz), 8.10–8.06 (m, 2H), 8.00–7.90 (m, 2H), 7.84 (s, 1H), 7.63–7.59 (m, 3H), 7.53 (s, 2H), 5.47 (s, 1H), 2.45 (s, 3H), 2.43 (s, 3H); MS (ESI) m/z: 473.

2.3.15 3-Amino-11,12-dimethyl-1-(4-bromo-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5o)

Yellow solid, M.P.: 293–295 °C; IR (KBr) ν (cm−1): 3471, 3361, 3173, 2181, 1657, 1616, 1591, 1480, 1403, 1383, 1341, 1292, 1261, 1204, 1161, 1103, 1055, 1008, 858, 824, 759; 1H NMR (400 MHz, DMSO-d6) δ: 9.20–9.18 (m, 1H), 8.44–8.42 (m, 1H), 8.00–7.91 (m, 3H), 7.83 (s, 1H), 7.41–7.38 (m, 4H), 7.35–7.31 (m, 2H), 5.45 (s, 1H), 2.48 (s, 3H), 2.49 (s, 3H); MS (ESI) m/z: 507.

2.3.16 3-Amino-11,12-dimethyl-1-(3-nitro-phenyl)-1H-benzo[a]pyrano[2,3-c]phenazine-2-carbonitrile (5p)

Yellow solid, M.P.: 275–277 °C; IR (KBr) ν (cm−1): 3472, 3329, 3201, 2198, 1711, 1662, 1627, 1590, 1525, 1470, 1387, 1341, 1293, 1264, 1203, 1163, 1100, 1049, 871, 763, 722; 1H NMR (400 MHz, DMSO-d6) δ: 9.22–9.20 (m, 1H), 8.47–8.45 (m, 1H), 8.25 (t, 1H, J = 2.0 Hz), 8.03–7.91 (m, 5H), 7.87 (s, 1H), 7.56 (d, 1H, J = 8.0 Hz), 7.53 (s, 2H), 5.69 (s, 1H), 2.53 (s, 3H), 2.51 (s, 3H); MS (ESI) m/z: 473.

3 Results and Discussion

In our initial quest for the optimization of the reaction conditions, we chose 2-hydroxynaphthalene-1,4-dione (1), o-phenylenediamine (2a), 4-Chlorobenzaldehyde (3b) and malononitrile (4) as model substrates for the synthesis of Benzo[a]pyrano[2,3-c]phenazine (5a). Initially, due to environmental concerns we chose water in place of widely used organic solvents as reaction medium. Throughout optimization studies, we scrutinized the effect of different catalysts, solvents and temperature on our model reaction. The results have been recapitulated in (Table 1).

Table 1 Optimization of reaction conditions
figure b
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In our preliminary pursuit, we took 2-hydroxynaphthalene-1,4-dione (1, 1.0 mmol) and o-phenylenediamine (2a, 1.0 mmol) in the absence of catalyst at room temperature using water as a solvent and found that product was not formed even after 24 h of stirring (Table 1, entry 1). After this, we attempted the same reaction at 70  °C, yet again formation of product did not take place effectively (Table 1, entry 2). In our next endeavour we used some phase transfer catalysts like cetyltrimethylammonium bromide (CTAB), tetradecyltrimethylammonium bromide (TTAB) and sodium dodecylsulfate (SDS) and observed that the product was formed in very small amount after 12 h of stirring (Table 1, entries 3–5). After that we tried our reaction with cyclodextrins (Table 1, entries 6–8) and observed that β-cyclodextrin in presence of water as a solvent at 70 °C gave the best result with 82% yield of the product within 1 h (Table 1, entry 7).

Once an apposite green catalyst had been recognized for fostering this reaction, we carried out a batch of experiments in presence of different solvents at 70 °C in order to inspect the effect of different solvents on the course of the reaction (Table 1, entries 9–15) and found that EtOH:H2O (1:1) as a solvent is the most appropriate for our proposed pathway (Table 1, entry 10). Subsequently, we performed a set of reactions with different concentrations of β-cyclodextrin (Table 1, entries 10 and 16–18) and concluded that 20 mol% of β-cyclodextrin is relevant for the present strategy which afforded a 91% yield of product (Table 1, entry 10).

Further, our ensuing effort involved the optimization of temperature for the current protocol (Table 1, entries 10 and 19–21). At first, we carried out the reaction at room temperature which gave only 25% yield of product in 12 h (Table 1, entry 19). Further we carried out the present protocol with 50 °C, 70 °C and 80 °C and the yield of product clearly demonstrated that 70 °C is the most suitable temperature for our synthetic strategy (Table 1, entry 10).

Consequently we managed to identify the optimized reaction conditions for the present transformation. Our reaction works well by using 20 mol% of β-cyclodextrin in EtOH:H2O (1:1) solvent at 70 °C, affording 91% yield of the product within 1 h with our model substrates.

Once the perfect reaction conditions had been identified, in order to ensure the versatility and generality of the proposed synthesis, the scope of the reported synthetic strategy was successfully evaluated (Scheme 2). We used different derivatives of o-phenylenediamine (2) and aromatic aldehydes (3) to achieve the illustrated pathway for the formation of target product (5a-p) in good to excellent yields. To our gratification, aromatic aldehydes (3) having both an electron withdrawing group and an electron donating group were well endured and afforded a significant yield of the product in all the instances.

Scheme 2
scheme 2

Substrate scope for 5. All reactions were carried out stirring with 1 (1.0 mmol), 2 (1.0 mmol), 3 (1.0 mmol) and 4 (1.0 mmol) using 20 mol% β- Cyclodextrin as catalyst in EtOH:H2O (1:1) solvent under air at 70 °C.

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3.1 Practicability of the Reaction

To set up the feasibility of the current protocol, we carried out the experiment on a large scale. For this we took our model substrates in a round bottom flask in presence of β-cyclodextrin in EtOH:H2O (1:1) solvent at 70 °C. 2-hydroxynaphthalene-1,4-dione (1, 10 mmol, 1.7415 g), o-phenylenediamine (2a, 10 mmol, 1.081 g), 4-chlorobenzaldehyde (3a, 10 mmol, 1.40 g) and malononitrile (4, 10 mmol) were reacted to obtain the dihydropyrano[2,3-c]pyrazole (5b) in 91% yield in about 50 min by using common laboratory glasswares at 70 °C (Scheme 3).

Scheme 3
scheme 3

Practicability of the Present methodology

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3.2 Recyclability of β-CD

The reusability of catalyst was explored by investigating it’s activity in six cycles in which the initial use of fresh catalyst for the synthesis of Benzo[a]pyrano[2,3-c]phenazine was also taken into account. In each cycle, the catalyst was almost quantitatively recovered and even after third and fourth use there was a negligible decrease in the quantity and in the effectiveness of the catalyst but after fourth cycle there was appreciable decrease in the quantity and in the effectiveness of the catalyst (Fig. 3).

Fig. 3
figure 3

Reuse and recovery of β-CD and its consequence on yield

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3.3 Mechanism

A plausible reaction mechanism reconcilable with the above results is depicted in Scheme 4. The desired product is expected to form by the Knoevenagel condensation followed by Michael addition and at last cyclization within the cavity of β-CD where it is anticipated that seven free primary –OH groups of β-CD execute synergistically as a proficient host and supramolecular catalyst [54, 55]. Reactants may form reversible non covalent supramolecular complexes within the cavity in order to increase the localized concentration that results in the dissolution of reactants in the aqueous medium. Initially, the condensation of 2-hydroxynaphthalene-1,4-dione (1) and diamine (2) takes place to afford the intermediate A. Similar condensation of aldehyde (3) and malanonitrile (4) occurs to form the intermediate B. After that, intermediate A reacts with intermediate B via Michael addition to yield an intermediate C. Finally, intermediate C undergo cyclization to afford the desired product 5.

Scheme 4
scheme 4

Plausible mechanism for Benzo[a]pyrano[2,3-c]phenazine derivatives (5a-p)

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4 Conclusion

In conclusion, we have reported a facile and convenient new pathway for the one-pot, multicomponent, sustainable green synthesis of highly functionalized and efficacious biologically significant scaffold Benzo[a]pyrano[2,3-c]phenazine and its derivatives in ethanol:water solvent at 70 °C in the catalytic activity of β-cyclodextrin. To the best of our knowledge this is the first synthesis of the title compound. The utilization of biodegradable, environmentally benign supramolecular catalyst as a recyclable catalyst and EtOH:H2O mixed green solvent system has engrossed substantial attention and has emerged as a hallmark of this transformation. The other key attributes of the disclosed protocol are operational feasibility, short reaction time, simple workup procedure, good to excellent yields of the product and easy recovery plus reusability of the catalyst. All these traits ascertain the disclosed methodology as superior to the previously reported methods.