Unexpected regiospecific Michael addition product: synthesis of 5,6-dihydrobenzo[1,7]phenanthrolines

Abstract

The unexpected formation of 5,6-dihydrobenzo[1,7]phenanthroline instead of 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitrile in acridine molecules using Michael addition has been observed for the first time. Moreover, we have identified Montmorillonite KSF clay as a catalyst to obtain regiospecific expected dihydrobenzo[1,7]phenanthroline-3-carbonitrile product and NaH for the regiospecific formation of unexpected Michael addition 5,6-dihydrobenzo[1,7]phenanthroline products. On the basis of a systematic study, the novel regiospecificity could be assigned by the utilization of a suitable catalyst.

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Introduction

Heterocyclics play an important part in agricultural, pharmacological, and synthetic fields. Consequently, there has been great progress in the methodologies for the assembly of molecules containing heterocyclic templates and it continues to attract the attention of both the academic and industrial societies. The investigation of the chemistry of acrinine has been one of the active area of heterocyclic chemistry. From an environmental and economic standpoint, it can be observed that the old-fashioned methods of chemical synthesis are unsustainable and have to be altered. Organic reactions carried out through multicomponent reactions (MCR) are an eye-catching area of investigation in on-going organic synthesis.¹ MCR are convergent reactions, in which three or more precursors react to form a product. These reactions show a tendency to form several bonds in one operation without isolating the intermediates, and would allow the minimization of waste production. A typical MCR is a flexible reaction for the rapid generation of complex molecules with often biologically relevant scaffold structures.¹ Using this technique, numerous significant investigations have been often accomplished by multidisciplinary research teams. Multicomponent coupling reactions are more efficient, cost effective and create less waste than traditional methods. The realization of the assembly of multiple bonds in MCR promotes a sustainable approach to new molecule discovery. The preparation of an efficient functionalized heterocyclic compound is one of the important tasks in organic synthesis. MCR is one of the methods that address the challenges for the development of eco-compatible reactions.¹ These MCR reactions have become one of the important methods for the rapid construction of heterocyclic compounds.^2,3 Unexpected chemical reactions reveal new types of chemical pathway and novel compounds in organic synthesis.^4–6 Literature surveys reveal that the synthesis of pyridine and pyrimidine analogues can be achieved via Michael reactions.⁷ Based on the literature survey, Michael addition forms only the presence of nitrile functional group in heterocyclic compounds.^8–11 In continuation of our earlier report in organic synthesis,^12–17 our current studies have focused on the multicomponent synthesis of heterocycles.¹⁸ We were interested in the straightforward construction of 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitrile synthesis; however, at this juncture, we have found that there is an unexpected formation of 5,6-dihydrobenzo[1,7]phenanthroline product. In continuation, we have herein reported the optimization of reaction conditions to obtain the regiospecific unexpected product as well as the expected one.

Results & discussion

Michael addition reaction is broadly documented as one of the vital C–C bond forming reactions in organic synthesis, and it can be commonly carried out with a strong base.¹⁹ Though, the base catalysed method occasionally suffers from drawbacks in the form of incompatibility with base-sensitive functionality and side reactions, such as retro-Michael type decompositions and autocondensations. Even though these methods are appropriate for synthetic applications, several of them are associated with some hindrances such as the need for toxic reagents, long durations, difficult workup and low yields. Thus, the development of new methods using cheap and commercially available less toxic reagents to afford high yields of products in short reaction times is important. Literature reveals that Michael addition in the presence of Et₃N²⁰ requires long heating periods, and the product yields were only moderate with the formation of side products.²¹ To avoid such problems, substantial attention has been recently focused on the use of phase transfer catalysts, transition metal complexes, clay supported catalysts, Lewis acid catalysts such as Yb(OTf)₃, ZrCl₄, BF₃·Et₂O, Bi(OTf)₃, and trifluoromethane sulfonic acid in Michael additions.^22–27 In this investigation, MCR has been carried out by the following synthetic strategy. The reaction of 7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one 1 with 4-cholorobenzaldehyde 2 and malononitrile 3 was carried out with various base catalysts (Table 1), which afforded the expected 10-chloro-4-(4-chlorophenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline-3-carbonitrile 4 and the unexpected 10-chloro-4-(4-chlorophenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline 5. The results are summarized in Table 1. Under the optimized reaction conditions, the base catalyst was varied from mild inorganic base to strong bases. The Michael reaction of β-functionalized or α,β-unsaturated carbonyls with malononitrile has been described. In Table 1, the optimization of the base catalyst is summarized. The mild base K₂CO₃ in ethanol and water (1 : 1) medium yields (Table 1, entry 3) less amount of expected compound 4 and a trace amount of unexpected compound 5. Furthermore, increasing the order of base catalyst yields a moderate amount of expected compound 4 (Table 1, entry 4) and less amount of unexpected compound 5.

Table 1 Effect of reaction conditions on the multicomponent reaction for 4b and 5b

Entry^a	Base/equiv.	Solvent (1 : 1)	Yield^b (%)
			4a	5a
a All reactions were carried out in 1 mmol of (1 : 1 : 1) equiv. of reactants (1, 2a and 3) and 5 mL of solvent unless otherwise noted.b Isolated yield.c TLC. The optimized conditions are mentioned in bold letters.
1	K2CO3/1	EtOH/water	—	—
2	K2CO3/3	EtOH/water	Trace^c	—
3	K2CO3/5	EtOH/water	30	Trace^c
4	K2CO3/10	EtOH/water	32	5
5	Na2CO3/10	EtOH/water	37	5
6	KOH/20	EtOH	53	9
7	NaOH/20	EtOH	55	17
8	Na/20	EtOH	57	19
9	NaH/5	EtOH	55	24
10	NaH/1	EtOH/benzene	43	27
11	NaH/2	EtOH/benzene	35	31
12	NaH/3	EtOH/benzene	23	39
13	NaH/4	EtOH/benzene	16	57
14	NaH/5	EtOH/benzene	10	68
15	NaH/6	EtOH/benzene	Trace^c	73
16	NaH/7	EtOH/benzene	Trace^c	78
17	NaH/8	EtOH/benzene	Trace^c	78
18	KSF/100 mg	EtOH	87	—
19	KSF/200 mg	EtOH	88	—
20	KSF/300 mg	EtOH	90	—
21	KSF/400 mg	EtOH	90	—

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Our aim is to optimize the reaction conditions to obtain the unexpected compound 5 regiospecifically. Depending on the basic nature, the reaction conditions vary from mild to strong basic. A strong base NaH plays major role in obtaining the unexpected product 5 (Table 1, entry 9). The solvents also influence the yield of the products. The 1 : 1 ratio of NaH in EtOH and benzene (Table 1, entry 10–17) increase the yield of the unexpected compound 5 and decrease the yield of the expected compound 4. The optimized conditions are NaH in EtOH/benzene (Table 1, entry 16), which give 78% of yield. Upon further increasing the amount of base, the yield percentage of the products is not altered. Our results extend our interest in obtaining the expected Michael product 4 regiospecifically. Towards this end, we have carried out the reaction using Montmorillonite KSF clay (KSF) as catalyst instead of the above mentioned bases (Table 1, entries 18–21), which regiospecifically yields 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitrile 4. The structure of compounds 4 and 5 were confirmed by ¹H NMR, ¹³C NMR and mass spectrometry (ESI†). The structure of the unexpected compound 5b was supported by X-ray crystallography studies. The ORTEP diagram is shown in Fig. 1.

Fig. 1 ORTEP for compound 5b.

Earlier in the literature, it was seen that the Michael addition offered the expected carbonitrile product alone. Moreover, no literature reports were available for the absence of carbonitrile functional group in acridine systems. In the present study, our aim is to focus on the synthesis of regiospecific unexpected product 5 and expected compound 4 in various 5,6-dihydrophenthroline analogues. From our optimized condition (Table 2), we have utilized various (E)-2-benzylidene-7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one derivatives 6a–h, and reacted them with malononitrile 3 in the presence of NaH as a strong base (entry 15) to regiospecifically obtain unexpected products 5a–h. The physical data of all the synthesized compounds 5a–h are summarized in Table 2.

Table 2 Synthesis of 5,6-dihydrobenzo[1,7]phenanthrolines 5(a–h)

Entry	R1	R2	R3	m.p. (°C)	Yield^a (%)
a Isolated yield.
5a	–Cl	–C6H5	3,4-OCH3	142–144	81
5b	–Cl	–C6H5	4-Cl	236–238	79
5c	–H	–C6H5	4-Cl	163–165	80
5d	–H	–CH3	4-Cl	195–197	76
5e	–Cl	–C6H5	2-Cl	160–162	75
5f	–Cl	–C6H5	2,5-OCH3	138–140	78
5g	–Cl	–C6H5	3-OCH3	146–148	75
5h	–Cl	–C6H5	H	150–152	75

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Furthermore, we have investigated the substrate scope for the formation of the product with two transformations. The results are shown in subsequent schemes, and the regiochemical outcomes of the reactions are examined. The mode of addition reactions influences the organic transformation, solvent and catalyst.²⁸ We have tried to obtain regiospecific 5,6-dihydrobenzo[1,7]phenanthroline 5 from 7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one. We have also synthesized an intermediate 2-(4-chlorobenzylidene)malononitrile 7 using 4-cholorobenzaldehyde 2 and malononitrile 3 in ethanol refluxed for 8 h. The intermediate 7 was further treated with 7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one 1 using an optimized condition (entry 15), which resulted in the formation of unexpected compound 5b (Scheme 1).

Scheme 1 An alternative route for the synthesis of 5,6-dihydrobenzo[1,7]phenanthroline, 5b.

Another methodology has been attempted for the regiospecific preparation of expected 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitrile 4 (Scheme 2). However, these methods suffer from some limitations such as low yield, poor regioselectivity, number of steps and prolonged reaction time.²⁹

Scheme 2 Synthesis of 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitriles via two steps.

Therefore, we decided to develop a mild, economical and complementary synthetic approach. To overcome this problem, we utilized Montmorillonite KSF clay as catalyst (Table 3).

Table 3 Scope of various dihydrobenzo[1,7]phenanthroline-3-carbonitriles 4(a–d)

Entry	R1	R2	R3	m.p. (°C)	Yield^a (%)
a Isolated yield.
4a	–Cl	–C6H6	3,4-OCH3	162–164	81
4b	–Cl	–C6H6	4-Cl	210–212	78
4c	–H	–C6H6	4-Cl	231–233	81
4d	–H	–CH3	4-Cl	230–232	72

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In this case, (E)-2-benzylidene-7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one 6 reacted with malononitrile 3 in the presence of KSF as catalyst containing 10 mL of ethanol and yielded 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitrile 4. The KSF as a catalyst for the optimized reaction conditions is presented in Table 1. The reproducibility of catalyst was studied for up to 3 cycles. The results are shown in Table 3.

The reproducibility of KSF catalyst was examined, and we have reported 3 consecutive cycles of the concerned reaction (Table 4). After the completion of reaction, the mixture was cooled to room temperature and poured into ice water with continuous stirring. The solid was filtered and dissolved in dichloromethane. The catalyst was filtered to dryness and recycled for subsequent reaction cycle.

Table 4 Reproducibility of Montmorillonite KSF catalyst

Run	Amount (mg)	Yield (%)
1	250	90
2	230	89
3	220	88

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A plausible reaction mechanism is proposed for the formation of the expected 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitrile 4.

(Path A) and the unexpected 5,6-dihydrobenzo[1,7]phenanthroline 5 (Path B) on the basis of the results obtained in Scheme 3. The investigation of these two transformations are carried out as per the reported method using cyclohexanone and α-tetralone analogues.^10,11 The results reveals that the corresponding carbonitrile functional group contains the expected Michael product.

Scheme 3 A plausible reaction mechanism for the formation of phenanthroline compounds, 4 and 5.

Conclusion

In conclusion, we have developed a regiospecific synthesis of 5,6-dihydrobenzo[1,7]phenanthrolines 5 using NaH as base by Michael addition reaction. The expected 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitriles 4 was obtained using Montmorillonite KSF clay as catalyst. These data have lead to the development of an alternative and straight forward mechanistic pathway for Michael addition reaction. This report provides an easy method for a direct access to regiospecific expected and unexpected compounds.

Experimental section

The purification of reaction products were carried out by chromatography using silica gel (200–300 mesh). Melting points were measured on an Elche Microprocessor based DT apparatus using an open capillary tube and are corrected with standard benzoic acid. FT-IR spectrum was recorded on a SHIMADZU Infrared spectrophotometer (400–4000 cm⁻¹; resolution: 1 cm⁻¹) using KBr pellets. NMR spectra were obtained in CDCl₃ or DMSO (¹H at 400 MHz and ¹³C at 100 MHz) and data are reported as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), and coupling constant(s) in Hz. ESI-MS data were obtained using ESI-MS Thermo Fleet ionization. Unless otherwise noted, all the reagents were obtained commercially and used without further purification.

Regiospecific synthesis of 5,6-dihydrobenzo[1,7]phenanthrolines 5(a–h)

A mixture of 4 equivalents (0.96 g) NaH was stirred with a solution containing 5 mL ethanol and 5 mL of benzene in ice cold condition at 15 min. A mixture of corresponding (E)-2-benzylidene-7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one, 6 (1 mmol) and malononitrile, 3 (1 mmol) was added to a solution containing NaH base. After the addition of the reagents and reactants, the reaction mixture was refluxed for 3 h at 80 °C. The reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was poured into ice cold water and neutralized with 2 N HCl. The precipitate was filtered and washed with water. The product was purified by column chromatography to obtain compound 5.

Regiospecific synthesis of 5,6-dihydrobenzo[1,7]phenanthroline-3-carbonitriles 4(a–d)

A mixture of (E)-2-benzylidene-7-chloro-9-phenyl-3,4-dihydroacridin-1(2H)-one, 6 (1 mmol), malononitrile, 3 (1 mmol) KSF in ethanol (10 mL) was refluxed for 3 h. The completion of reaction was noted by TLC. The catalyst was recovered and reused for more three times. The product was purified by column chromatography. The process offered the expected compound, 4.

The spectral characterization of the synthesized compounds are listed below.

10-Chloro-4-(3,4-dimethoxyphenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline-3-carbonitrile (4a). Orange solid; yield 81%; mp: 162–164 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 2225 (CN), 1541, 1516 (C–O–C); ¹H NMR (CDCl₃): δ (ppm), 1.08 (t, J = 6.8 Hz, 3H), 2.98 (t, J = 6.8 Hz, 2H), 3.17–3.29 (m, 4H), 3.90 (s, 3H), 3.94 (s, 3H), 6.51 (s, 1H), 6.88 (d, J = 8 Hz, 1H), 6.94 (d, J = 8 Hz, 2H), 7.29 (s, 1H), 7.39–7.48 (m, 4H), 7.59 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H); ¹³C NMR (CDCl₃): δ (ppm), 14.4, 24.5, 29.7, 56.0, 61.2, 110.3, 110.9, 112.0, 121.9, 125.4, 125.8, 126.9, 128.0, 128.3, 129.2, 129.6, 130.1, 130.1, 131.2, 133.7, 138.8, 144.5, 145.4, 148.8, 149.0, 149.2, 151.1, 161.2, 161.3; ESI-MS: m/z 548.58.

10-Chloro-4-(4-chlorophenyl)-2-ethoxy-12-phenyl-5,6-dihydro benzo[j][1,7]phenanthroline-3-carbonitrile (4b). Yellow solid; yield 78%; mp: 210–212 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 2222 (CN), 1544, 1492 (C–O–C); ¹H NMR (400 MHz, CDCl₃) δ 1.12 (t, J = 14.4 Hz, 3H), 2.81 (t, J = 8.25 Hz, 2H), 3.18 (t, J = 13.2 Hz, 2H), 3.31–3.36 (m, 2H), 7.25–7.32 (m, 5H), 7.47–7.52 (m, 5H), 7.99 (d, J = 8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 14.1, 24.3, 33.5, 63.0, 115.0, 125.3, 125.5, 126.1, 127.4, 128.6, 129.0, 129.2, 129.5, 129.6, 130.1, 130.2, 130.6, 131.2, 132.3, 133.3, 135.8, 138.1, 146.0, 146.5, 153.3, 153.6, 160.5, 161.9; ESI-MS: m/z 522.23.

4-(4-Chloro-phenyl)-2-ethoxy-12-phenyl-5,6-dihydro-benzo[j][1,7]phenanthroline-3-carbonitrile (4c). Pale yellow solid; yield 81%; mp: 231–233 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 2220 (CN), 1545, 1495 (C–O–C); ¹H NMR (400 MHz, CDCl₃) δ 1.05 (t, J = 7.2 Hz, 3H), 2.75 (t, J = 6.8 Hz, 2H), 3.14 (t, J = 7.2 Hz, 2H), 3.32–3.30 (m, 2H), 7.31 (d, J = 6.8 Hz, 2H), 7.41–7.57 (m, 7H), 7.66 (d, J = 7.2 Hz, 2H), 7.79 (t, J = 7.2 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H); ¹³C NMR (400 MHz, CDCl₃): δ 14.4, 24.4, 26.9, 34.1, 61.2, 110.0, 124.9, 125.9, 126.6, 127.1, 128.1, 128.4, 128.5, 128.7, 129.5, 129.6, 130.1, 134.3, 134.4, 137.2, 139.5, 145.6, 147.0, 149.8, 150.1, 160.7, 161.5; ESI-MS: m/z 488.26.

4-(4-Chloro-phenyl)-2-ethoxy-12-methyl-5,6-dihydro-benzo[j][1,7]phenanthroline-3-carbonitrile (4d). Pale yellow solid; yield 72%; mp: 230–232 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 2225 (CN), 1549, 1493 (C–O–C); ¹H NMR (400 MHz, CDCl₃) δ 1.52 (t, J = 8 Hz, 3H), 2.76 (t, J = 6.8 Hz 2H), 3.09 (t, J = 6.4 Hz, 2H), 3.15 (s, 3H), 4.57–4.63 (m, 2H), 7.33 (d, J = 8 Hz, 2H), 7.53 (d, J = 8 Hz, 2H), 7.59 (t, J = 7.6 Hz, 1H), 7.74 (t, J = 7.2 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H); ¹³C NMR (400 MHz, CDCl₃): δ 14.6, 17.3, 24.6, 33.5, 63.5, 94.5, 115.1, 124.9, 125.8, 126.0, 126.3, 128.6, 129.1, 129.2, 130.1, 130.3, 133.5, 135.7, 144.7, 147.1, 153.4, 155.1, 159.9, 162.1; ESI-MS: m/z 426.27.

10-Chloro-4-(3,4-dimethoxyphenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline (5a). White solid; yield 81%; mp: 142–144 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1552, 1477 (C–O–C); ¹H NMR (400 MHz, CDCl₃): δ 1.12 (t, J = 6.8 Hz, 3H), 2.88–2.90 (m, 2H), 3.16–3.17 (m, 2H), 3.32–3.34 (m, 2H), 3.91 (s, 3H), 3.95 (s, 3H), 6.86 (s, 1H), 6.94 (d, J = 8 Hz, 1H), 7.00 (d, J = 8 Hz, 1H), 7.24 (d, J = 6 Hz, 1H), 7.44–7.51 (m, 6H), 7.63 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H); ¹³C NMR (100 Hz, CDCl₃): δ 14.3, 24.6, 33.8, 56.1, 56.2, 62.9, 95.3, 111.3, 112.1, 115.5, 121.8, 125.7, 126.0, 126.1, 127.3, 127.5, 128.6, 129.1, 129.5, 130.4, 131.2, 132.3, 138.3, 146.1, 146.4, 149.1, 150.1, 153.1, 154.8, 160.8, 162.0; ESI-MS: m/z 523.02.

10-Chloro-4-(4-chlorophenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline (5b). Yellow solid; yield 79%; mp: 236–238 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1544, 1492 (C–O–C); ¹H NMR (400 MHz, CDCl₃): δ 1.07 (t, J = 7.2 Hz, 3H), 2.92 (t, J = 7.2 Hz, 2H), 3.15–3.28 (m, 4H), 6.46 (s, 1H), 7.38–7.47 (m, 8H), 7.58–7.60 (m, 2H), 7.98 (d, J = 8.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): δ 14.3, 24.3, 34.0, 61.2, 110.3, 125.0, 125.8, 126.6, 126.9, 128.3, 128.7, 129.2, 129.5, 130.1, 130.2, 131.8, 134.3, 137.0, 138.8, 144.6, 145.3, 149.3, 150.0, 161.1, 161.2; ESI-MS: m/z 497.26.

4-(4-Chloro-phenyl)-2-ethoxy-12-phenyl-5,6-dihydro-benzo[j][1,7]phenanthroline (5c). Yellow solid; yield 80%; mp: 163–165 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1545, 1493 (C–O–C); ¹H NMR (400 MHz, CDCl₃) δ 1.01–0.99 (t, J = 7.2 Hz, 3H), 2.90–2.87 (t, J = 7.6 Hz, 2H), 3.11 (t, J = 5.6 Hz, 2H), 3.24–3.19 (m, 2H), 6.52 (s, 1H), 7.27 (d, J = 7.2 Hz, 2H), 7.51–7.38 (m, 7H), 7.56 (d, J = 8.4 Hz, 2H), 7.78 (t, J = 7.6 Hz, 1H), 8.00 (d, J = 7.6 Hz, 1H); ¹³C NMR (400 MHz, CDCl₃) δ 14.2, 24.4, 33.6, 62.9, 94.6, 115.1, 124.5, 125.4, 126.4, 127.1, 127.4, 128.1, 128.3, 128.6, 129.2, 129.5, 130.1, 130.4, 133.4, 135.7, 138.8, 147.5, 147.5, 147.6, 153.4, 153.8, 160.1, 161.9; ESI-MS: m/z 463.37.

4-(4-Chloro-phenyl)-2-ethoxy-12-methyl-5,6-dihydro-benzo[j][1,7]phenanthroline (5d). Yellow solid; yield 76%; mp: 195–197 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1545, 1495 (C–O–C); ¹H NMR (400 MHz, CDCl₃) δ 1.45 (t, J = 7.2 Hz, 3H), 2.87 (t, J = 7.2 Hz, 2H), 3.09 (t, J = 6.0 Hz, 2H), 3.16 (s, 3H) 4.50–4.45 (m, 2H), 6.65 (s, 1H), 7.3 (d, J = 8.4 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H) 7.55 (t, J = 7.6 Hz, 1H), 7.70–7.67 (t, J = 7.2 Hz, 1H), 8.01 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H); ¹³C NMR (400 MHz, CDCl₃) δ 13.8, 16.0, 23.6, 33.0, 60.8, 108.6, 123.6, 124.4, 124.8, 126.0, 127.7, 127.8, 127.9, 128.3, 129.1, 133.3, 136.2, 141.7, 145.5, 149.1, 150.2, 159.5, 160.3; ESI-MS: m/z 401.36.

10-Chloro-4-(2-chlorophenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline (5e). White solid; yield 75%; mp: 160–162 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1546, 1481 (C–O–C); ¹H NMR (400 MHz, CDCl₃): δ 1.08 (t, J = 7.2 Hz, 3H), 2.60–2.67 (m, 2H), 2.78–2.85 (m, 2H), 3.17–3.26 (m, 2H), 6.41 (s, 1H), 7.34–7.36 (m, 2H), 7.40–7.50 (m, 8H), 7.58 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 14.5, 23.9, 34.0, 61.3, 110.9, 125.9, 126.2, 126.7, 127.0, 128.4, 128.5, 129.4, 129.5, 129.6, 130.2, 130.3, 130.6, 131.8, 132.9, 137.7, 139.1, 144.7, 145.4, 148.8, 161.2, 161.4; ESI-MS: m/z 497.46.

10-Chloro-4-(2,5-dimethoxyphenyl)-2-ethoxy-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline (5f). White solid; yield 78%; mp: 138–140 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1552, 1477 (C–O–C); ¹H NMR (400 MHz, CDCl₃): δ 1.11–1.14 (t, J = 6.0 Hz, 3H), 2.88–2.90 (m, 2H), 3.17–3.18 (m, 2H), 3.33–3.34 (m, 2H), 3.91 (s, 3H), 3.95 (s, 3H), 6.86 (s, 1H), 6.94 (d, J = 8 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 8 Hz, 1H), 7.44–7.51 (m, 6H), 7.63 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 14.3, 24.6, 33.8, 56.1, 56.2, 62.9, 95.3, 111.3, 112.1, 115.5, 121.8, 125.7, 126.0, 126.1, 127.3, 127.5, 128.6, 129.1, 129.5, 130.4, 131.2, 132.3, 138.3, 146.1, 146.4, 149.1, 150.1, 153.1, 154.8, 160.8, 162.0; ESI-MS: m/z 522.23.

10-Chloro-2-ethoxy-4-(3-methoxyphenyl)-12-phenyl-5,6-dihydrobenzo[j][1,7]phenanthroline (5g). Yellow solid; yield 75%; mp: 146–148 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1558, 1543, 1442 (C–O–C); ¹H NMR (400 MHz, CDCl₃): δ 1.06–1.09 (t, J = 6.8 Hz, 3H), 2.94 (t, J = 6.8 Hz, 2H), 3.16 (t, J = 6.0 Hz, 2H), 3.22–3.28 (m, 2H), 3.84 (s, 3H), 6.50 (s, 1H), 6.87 (s, 1H), 6.93 (t, J = 8.4 Hz, 2H), 7.25–7.29 (m, 2H), 7.34–7.41 (m, 2H), 7.44–7.46 (m, 3H), 7.58 (d, J = 8.8 Hz, 1H), 7.98 (d, J = 9.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 14.5, 24.5, 34.3, 55.4, 61.3, 110.5, 113.7, 114.5, 121.3, 125.5, 125.9, 126.9, 127.0, 128.4, 129.4, 129.6, 129.7, 130.2, 130.3, 131.8, 139.0, 140.1, 144.7, 145.5, 149.3, 151.3, 159.7, 161.3, 161.4; ESI-MS: m/z 493.40.

10-Chloro-2-ethoxy-4, 12-diphenyl-5,6-dihydrobenzo[j][1,7]phenanthroline (5h). Brown solid; yield 75%; mp: 150–152 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 1552, 1477 (C–O–C); ¹H NMR (400 MHz, CDCl₃): δ 1.13 (t, J = 6.8 Hz, 3H), 2.81–2.84 (t, J = 6.4 Hz, 2H), 3.17 (t, J = 5.6 Hz, 2H), 3.31–3.36 (m, 2H), 7.15–7.36 (m, 4H), 7.44–7.50 (m, 8H), 7.63 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃): δ 14.3, 24.4, 33.7, 62.9, 95.3, 115.2, 124.5, 124.5, 125.5, 125.8, 126.1, 126.8, 127.5, 128.0, 128.4, 128.6, 128.7, 128.9, 129.1, 129.4, 129.5, 130.2, 130.3, 131.2, 132.3, 132.5, 132.6, 135.1, 136.9, 138.3, 146.0, 146.4, 147.1, 153.1, 155.0, 160.8, 161.9; ESI-MS: m/z 462.29.

2-Amino-10-choloro-5,6-dihydro-4-(3,4-dimethoxyphenyl)-12-pheny-4H-pyrano[2,3-a]acridine-3-carbonitrile (8a). White solid; yield 90%; mp: 206–208 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 2372, 2193 (CN), 3448 (NH₂); ¹H NMR (400 MHz, CDCl₃): δ 2.07–2.11 (m, 1H), 2.38–2.42 (m, 1H), 2.97–2.91 (m, 1H), 3.07–3.10 (m, 1H), 3.7 (s, 6H) 4.0 (s, 1H, CH), 4.9 (bs, 2H), 6.70–8.00 (m, 11H); ¹³C NMR (100 MHz, CDCl₃): δ 23.57, 32.15, 42.10, 55.42, 55.37, 111.17, 111.95, 118.37, 119.65, 119.81, 120.74, 124.45, 127.68, 127.88, 128.03, 128.18, 128.55, 128.73, 129.74, 130.54, 130.87, 135.72, 137.47, 139.56, 139.78, 144.29, 148.02, 148.84, 158.03, 158.98; ESI-MS: m/z 522.23.

2-Amino-10-choloro-4-(4-chlorophenyl)-5,6-dihydro-12-pheny-4H-pyrano[2,3-a]acridine-3-carbonitrile (8b). Yellow solid; yield 82%; mp: 154–156 °C; FT-IR (KBr pellet) ν_max/(cm⁻¹): 2372, 2191 (CN), 3446 (NH₂); ¹H NMR (400 MHz, CDCl₃): δ 2.15–2.20 (m, 1H), 2.39–2.41 (m, 1H), 2.99–3.06 (m, 1H), 3.12–3.16 (m, 1H), 4.0 (s, 1H), 3.4 (bs, 2H), 7.17–7.95 (m, 12H); ¹³C NMR (100 MHz, CDCl₃) δ 24.04, 32.82, 42.75, 59.73, 117.26, 119.22, 120.53, 125.57, 127.72, 128.14, 128.32, 128.56, 129.07, 129.20, 129.32, 129.42, 130.33, 130.60, 132.51, 133.75, 138.70, 140.64, 141.08, 141.18, 145.13, 158.22, 158.39; ESI-MS: m/z 495.35.

Acknowledgements

The authors thank DST-SERB (no. SB/FT/CS-126/2012), Government of India, New Delhi for providing the research grants. The authors wish to express their gratitude to DST-FIST for providing NMR facility to VIT-SIF, VIT University, Vellore, Tamil nadu, India.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. CCDC 988643. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra16640j

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