Ligand-free palladium-catalyzed facile construction of tetra cyclic dibenzo[b,h][1,6]naphthyridine derivatives: domino sequence of intramolecular C–H bond arylation and oxidation reactions

Abstract

A ligand-free Pd-catalyzed approach has been developed for the synthesis of dibenzo-fused naphthyridines. The reaction involves a one-pot domino sequence of reactions involving C–H functionalisation and oxidation. The reaction was applicable to a wide range of substrates, giving the required product. Further fluorescence studies were performed where the Stoke's shift was found to be dependent on the polarity of the solvent.

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Introduction

Naphthyridines and their benzo-fused analogues are important structural motifs in various natural products.¹ They exhibit a broad range of biological activities prominent amongst them, being anti-inflammatory,^2a anti-tumour,^2b and anticancer activities,^3a and activity as HIV-1 integrase inhibitors,^3b and AKt1 and AKt2 inhibitors.^3c In particular 1,6-naphthyridines have been shown to have drug like properties.⁴ Apart from their biological activities, fluorescent naphthyridine derivatives have been used as luminescence materials in molecular recognition⁵ and fluorescence detection.⁶ Owing to spectrum of biological activities and fluorescent properties various methods have been reported for the synthesis of 1,6-naphthyridine⁷ and their fused analogues.⁸ However there is always a need of better and more economical approaches to access such privilege skeletons. Importantly dibenzo fused 1,6-naphthyridine skeleton has received less attention towards its synthesis.⁹ Okuma^9aet al. have used domino sequence of reactions for their synthesis while Wang^9b and co workers have used Sc(OTf)₃ mediated cyclization. However, most of the methods suffer from some drawbacks such as harsh reaction conditions and/or use of expensive precursors. C–H activation/functionalization¹⁰ has appeared as a valuable alternative over existing methods as it does not require pre functionalized molecules, thus reducing the steps and cost of synthesis.

During the last few years, 2-chloroquinoline-3-carboxaldehyde 1a has emerged as a versatile precursor for the synthesis of various benzo/hetero fused skeletons and has been extensively employed by us¹¹ and others.¹² As part of our ongoing research program¹³ we became interested in the synthesis of benzo fused 1,6-naphthyridine via C–H functionalization. We envisioned that 2-chloroquinoline-3-carboxaldehyde^11e derived amine 2a could undergo intramolecular C–H functionalisation leading to annulation which upon subsequent oxidation could lead to synthesis of dibenzo fused 1,6-naphthyridine 3a (Fig. 1).

Fig. 1 Proposed synthetic route.

Result and discussion

To test this hypothesis, the required precursor 2a was prepared in one pot by condensation of aldehyde with aniline followed by reduction of resulting Schiff base (Scheme 1). With the required precursor in hand we set out to investigate the annulation reaction. The reaction of 2a was initially examined under coupling conditions, using 5 mol% of Pd(OAc)₂, 10 mol% of PPh₃, 2.5 equivalent of NaOAc in 2 mL of DMA at 130 °C for 17 h under N₂ atmosphere. We were delighted to obtain the cyclized product 3a in 69% yield (entry-1, Table 1). Structure of 3a was characterized as dibenzo[b,h][1,6]naphthyridine from its spectral and analytical data. The formation of 3a could be attributed to intramolecular cyclization by C–H arylation followed by dehydrogenation of 2a, demonstrating the instability of intermediate 5,6-dihydro dibenzo[b,h][1,6]naphthyridine. Encouraged by this result, the reaction was screened for optimized reaction condition. Use of PdCl₂(PPh₃)₂, also led to the formation of product 3a in 67% yield (entry 2). When annulation reaction was investigated in ligand free conditions using 5 mol% each of Pd(OAc)₂ and PdCl₂, the reaction got completed in 18 and 12 h giving product in 70% and 84% yields respectively (entries 3 & 4). Further change of loadings of the catalyst PdCl₂ (entries 5 and 6), bases (entries 7–8), solvents (entries 9–11) and temperatures (entries 12–13) didn't lead to better result. As a control experiment no product was obtained in absence of catalyst (entry 14). Conducting reaction under open atmosphere lead to reduction of yield (entry 15).

Scheme 1 Synthesis of required precursor 2a.

Table 1 Optimization of reaction condition

S. no.^a	Catalyst (mol%)	Solvent	Base	Temp. (°C)	Time (h)	Yield^b (%)
a All reactions were carried out on 0.5 mmol scale under N2 atmosphere. b Isolated yield. c Reaction was carried out in presence of 10 mol% of TPP. d Reaction was carried out under open atmosphere.
1^c	Pd(OAc)2 (5)	DMA	NaOAc	130	17	69
2	PdCl2(PPh3)2 (5)	DMA	NaOAc	130	16	67
3	Pd(OAc)2 (5)	DMA	NaOAc	130	18	70
4	PdCl 2 (5)	DMA	NaOAc	130	12	84
5	PdCl2 (2.5)	DMA	NaOAc	130	20	72
6	PdCl2 (7.5)	DMA	NaOAc	130	10	80
7	PdCl2 (5)	DMA	Et3N	130	24	30
8	PdCl2 (5)	DMA	K2CO3	130	24	40
9	PdCl2 (5)	DMF	NaOAc	130	14	76
10	PdCl2 (5)	DMSO	NaOAc	130	24	20
11	PdCl2 (5)	Toluene	NaoAc	130	24	20
12	PdCl2 (5)	DMA	NaOAc	100	24	65
13	PdCl2 (5)	DMA	NaOAc	150	12	70
14	—	DMA	NaOAc	130	24	—
15^d	PdCl2 (5)	DMA	NaOAc	130	24	30

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Next we set out to explore the generality of palladium catalyzed intramolecular cyclisation reactions on different substrates. Different anilines with quionline precursor were examined. Results obtained are summarized in Table 2. All reactions proceeded smoothly and were completed in 12–16 h, affording the required products 3b–3h in good yields. Electron donating group on aniline moiety at o,m,p-position required relatively longer reaction time, as compared to electron withdrawing group.

Table 2 The scope of palladium catalyzed intramolecular cyclization reaction

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However, yields obtained were in similar range (78–86%). Reaction worked well on differentially substituted anilines (3i, 3j). The generality of the cyclisation reaction was further extended on different anilino methyl quinoline. Similar trend of electronic effect was observed. Electron donating group present at 6,7-position showed lower reaction rate (3k–3n) as compared to electron withdrawing group (3o). Reaction was equally applicable with variation on both aryl fragments (3p, 3q). The synthetic potential of reaction was further validated by carrying out reaction of 2a on 1.07 g (4.0 mmol) scale, delivering the product 3a in 78% yield.

We were also able to get crystal structure of 3h which further confirmed the structure (Fig. 2).¹⁴ A plausible mechanism is presented (Scheme 2). Oxidative addition of Pd(0) to 2a gives A which upon C–H insertion gives B. Reductive elimination from B leads to intermediate C. Subsequently Pd mediated oxidation of C leads to formation of 3avia D.

Fig. 2 ORTEP diagram of 3h.

Scheme 2 Plausible mechanism.

We further investigated the photophysical properties of 3n by ultraviolet spectra and fluorescence spectra in different solvents. Solvatochromic behaviour of 3n (10 μM) was examined in nonpolar, polar protic and polar aprotic solvents such as, hexane, toluene, MeOH, DMF, DMSO and ethyl acetate (Fig. 3 and Table 3). On increasing the polarity of the medium, emission spectrum of 3n showed increase in Stoke's shift (Δυ) and ICT band shifted toward longer wavelength (e.g. λ_em = 407 nm (hexane), 413 nm (toluene), 429 nm (MeOH), 430 nm (ethyl acetate), 436 nm (DMSO), 483 nm (DMF). Accordingly, the color of 3n solution changed from a light blue to dark blue-green color (Fig. 2 inset). This could be attributed to variation in polarity, polarizability and H-bond accepting ability of solvents. The high sensitivity of the emission spectra of 3n to solvent may be due to a charge shift away from the methoxy group in the excited state, towards the electron acceptor quinoline group. This led to generation of large dipole moment in the excited state, which interacted with the polar solvent molecules to reduce the energy of the excited state. This led to emission at lower energies and longer wavelengths.

Fig. 3 Solvatochromic behaviour of 3n in different solvents (a) absorption and (b) emission spectra. Inset color change of 3n in different solvents.

Table 3 Solvatochromic behaviour of 3n

S. no.	Solvent	λ max	λ em	ε (cm^−1 M^−1)	Δ[small upsilon, Greek, macron] (nm)
1	Hexane	384	407	9.2 × 10^2	23
		364		6.2 × 10^2	43
2	Toluene	385	413	9.7 × 10^3	28
		366		9.8 × 10^3	47
3	MeOH	382	429	1.17 × 10^4	47
		363		1.23 × 10^4	66
4	Ethyl acetate	382	430	1.0 × 10^4	48
		363		1.06 × 10^4	67
5	DMSO	384	436	1.05 × 10^4	52
		365		1.16 × 10^4	71
6	DMF	383	483	9.3 × 10^3	100
		364		9.8 × 10^3	119

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Conclusions

In conclusion a domino sequence involving ligand free approach for Pd catalyzed intramolecular C–H arylation followed by oxidation has been developed for the synthesis of fused dibenzo 1,6-naphthyridine skeleton. Reaction was applicable to various substrates. Further fluorescence studies were also carried out. Stoke's shift was found to be dependent on polarity of solvent.

Experimental

General remarks

Melting points were measured using Buchi melting-point apparatus in an open capillary tube and are uncorrected. IR spectra were recorded on VARIAN 3300 FTIR spectrophotometers. ¹H NMR and ¹³C NMR were recorded on JEOL at (300 & 500) and (75 & 125) MHz spectrometer respectively. Chemical shifts (δ) are reported relative to TMS (¹H NMR), CDCl₃ (¹³C NMR) as the internal standards. High resolution mass spectra (HRMS) were obtained on micro TOF QII high-resolution mass spectrometer (ESI) and 6200 series TOF/6500 SRIES QTOF B.05.00 (B5042.0). Thin layer chromatography (TLC) was performed on glass plates (7.5 × 2.5 and 7.5 × 5.0 cm) coated with Loba Chemie's silica gel GF254. Visualization of spots was accomplished by exposure to UV light. Commercially available solvents were purified according to literature. Column chromatography was performed using silica gel (100–200). The electronic spectra and UV-visible titrations were carried out at room temperature (298 K) on a UV-1700/1800 Pharmaspec spectrophotometer with quartz cuvette (path length = 1 cm). The emission spectra were recorded at JY HORIBA fluorescence spectrophotometer. Due to ¹⁹F coupling additional peaks were observed in ¹³C NMR of 3h.

Representive procedure for the synthesis of dibenzo[b,h][1,6]naphthyridine derivatives 3a–q

Palladium chloride (5 mol%) and sodium acetate (2.5 eq.) were added to a solution of aryl amine 2a (0.5 mmol) in DMA (2 mL) and stirred at 130 °C for 12 h under N₂ atmosphere. Water was added to reaction mixture and it was extracted with EtOAc. Organic phase was then washed with water, brine and dried over Na₂SO₄. Solvent was then removed under reduced pressure and the residue obtained was purified by column chromatography (hexane : ethyl acetate (17 : 3)) to afford 3a.

Dibenzo[b,h][1,6]naphthyridine (3a)¹⁵. Reaction time: 12 h; yield: 84%; orange solid; mp: 174–178 °C; IR (KBr): ν 763, 1600 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.65–7.70 (m, 1H), 7.77–7.82 (m, 1H), 7.84–7.89 (m, 1H), 7.92–7.97 (m, 1H), 8.12 (d, J = 8.1 Hz, 1H), 8.20 (d, J = 8.1 Hz, 1H), 8.40 (d, J = 8.4 Hz, 1H), 8.88 (s, 1H), 9.34 (d, J = 7.8 Hz, 1H), 9.41 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 119.56, 124.33, 125.21, 126.54, 127.01, 127.67, 128.67, 129.49, 129.73, 130.66, 131.87, 137.13, 145.95, 147.83, 150.26, 154.12; HRMS (ESI) exact mass calcd for C₁₆H₁₀N₂H: 231.0922 (M + H)⁺, found: 231.0912 (M + H)⁺.

4-Methyl-dibenzo[b,h][1,6]naphthyridine (3b). Reaction time: 16 h; yield: 80%; brown solid; mp: 170–174 °C; IR (KBr): ν 744, 769 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 2.90 (s, 3H), 7.63–7.71 (m, 3H), 7.90–7.95 (m, 1H), 8.11 (d, J = 8.7 Hz, 1H), 8.39 (d, J = 8.4 Hz, 1H), 8.88 (s, 1H), 9.22 (d, J = 7.5 Hz, 1H), 9.42 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 18.44, 119.28, 122.16, 125.10, 126.42, 127.00, 127.28, 128.63, 129.79, 131.74, 136.99, 137.23, 144.54, 148.21, 150.27, 152.56; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂H: 245.1078 (M + H)⁺, found: 245.1093 (M + H)⁺.

1-Methyl-dibenzo[b,h][1,6]naphthyridine (3c). Reaction time: 16 h; yield: 79%; brown solid; mp: 140–144 °C; IR (KBr): ν 748, 1603 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 2.64 (s, 3H), 7.60–7.65 (m, 2H), 7.93–7.98 (m, 2H), 8.10 (d, J = 7.8 Hz, 1H), 8.37 (d, J = 8.1 Hz, 1H), 8.85 (s, 1H), 9.20 (d, J = 7.8 Hz, 1H), 9.37 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 21.79, 119.45, 122.82, 124.01, 124.15, 126.34, 126.88, 128.73, 129.27, 129.71, 131.84, 137.09, 141.21, 146.07, 148.00, 150.35, 154.04; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂H: 245.1078 (M + H)⁺, found: 245.1073 (M + H)⁺.

2-Methyl-dibenzo[b,h][1,6]naphthyridine (3d). Reaction time: 16 h; yield: 78%; brown solid; mp: 134–138 °C; IR (KBr): ν 825, 1605 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 2.70 (s, 3H), 7.64–7.69 (m, 2H), 7.92–7.97 (m, 1H), 8.08–8.13 (m, 2H), 8.40 (d, J = 8.4 Hz, 1H), 8.87 (s, 1H), 9.13 (s, 1H), 9.35 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 21.83, 119.69, 123.87, 124.97, 126.54, 127.04, 128.74, 129.18, 129.71, 131.90, 132.24, 137.21, 138.01, 144.06, 147.82, 150.26, 153.06; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂H: 245.1078 (M + H)⁺, found: 245.1095 (M + H)⁺.

4-Chloro-dibenzo[b,h][1,6]naphthyridine (3e). Reaction time: 12 h; yield: 85%; white solid; mp: 196–198 °C; IR (KBr): ν 747, 778 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.66–7.71 (m, 2H), 7.93–7.98 (m, 2H), 8.12 (d, J = 8.1 Hz, 1H), 8.37 (d, J = 8.7 Hz, 1H), 8.92 (s, 1H), 9.27 (d, J = 8.1 Hz, 1H), 9.50 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 119.32, 123.22, 126.96, 127.06, 127.21, 127.71, 128.73, 129.83, 131.13, 132.26, 133.70, 137.47, 142.14, 147.29, 150.48, 154.64; HRMS (ESI) exact mass calcd for C₁₆H₉ClN₂H: 265.0533 (M + H)⁺, found: 265.0542 (M + H)⁺.

1-Chloro-dibenzo[b,h][1,6]naphthyridine (3f). Reaction time: 12 h; yield: 86%; white solid; mp: 190–192 °C; IR (KBr): ν 745, 836, 1599 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.68–7.74 (m, 2H), 7.95 (s, 1H), 8.12 (d, J = 6.3 Hz, 1H), 8.17 (s, 1H), 8.37 (d, J = 8.6 Hz, 1H), 8.88 (s, 1H), 9.26 (dd, J = 8.4, 3.0 Hz, 1H), 9.41 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 119.44, 123.73, 125.66, 126.79, 127.09, 128.12, 128.75, 128.88, 129.74, 132.20, 136.46, 137.31, 146.61, 147.25, 150.44, 155.30; HRMS (ESI) exact mass calcd for C₁₆H₉ClN₂H: 265.0532 (M + H)⁺, found: 265.0523 (M + H)⁺.

2-Chloro-dibenzo[b,h][1,6]naphthyridine (3g). Reaction time: 12 h; yield: 83%; orange solid; mp: 176–178 °C; IR (KBr): ν 830, 1486, 1606 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.67–7.72 (m, 1H), 7.79 (dd, J = 8.4, 2.1 Hz, 1H), 7.94–7.99 (m, 1H), 8.10–8.15 (m, 2H), 8.39 (d, J = 8.7 Hz, 1H), 8.89 (s, 1H), 9.29 (d, J = 2.1 Hz, 1H), 9.38 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 119.54, 121.10, 123.78, 126.98, 127.27, 128.72, 129.02, 129.82, 130.98, 132.23, 133.76, 137.17, 144.25, 146.74, 150.33, 154.24; HRMS (ESI) exact mass calcd for C₁₆H₉ClN₂H: 265.0532 (M + H)⁺, found: 265.0524 (M + H)⁺.

2-Fluoro-dibenzo[b,h][1,6]naphthyridine (3h). Reaction time: 15 h; yield: 80%; brown solid; mp: 164–166 °C; IR (KBr): ν 832, 1491 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.53–7.60 (m, 1H), 7.67–7.72 (m, 1H), 7.93–7.98 (m, 1H), 8.12–8.20 (m, 2H), 8.39 (d, J = 8.7 Hz, 1H), 8.89 (s, 1H), 8.95 (dd, J = 9.3, 2.7 Hz, 1H), 9.36 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 109.29, 109.61, 118.84, 119.17, 119.41, 126.92, 127.28, 128.70, 129.82, 131.56, 131.67, 132.08, 137.15, 142.65, 147.16, 150.18, 153.16, 160.08, 163.36; HRMS (ESI) exact mass calcd for C₁₆H₉FN₂H: 249.0828 (M + H)⁺, found: 249.0820 (M + H)⁺; crystal data: bond precision: C–C = 0.0030 A; wavelength = 0.71073; cell: a = 10.153(5) b = 10.171(5) c = 12.242(5); alpha = 77.609(5) beta = 78.327(5) gamma = 75.424(5); temperature: 293 K; volume: 1180.2(10); space group: P1̄; sum formula: C₁₆H₉FN₂; M_r: 248.25; D (g⁻¹ cm⁻³): 1.396; Z: 4; M_u (mm⁻¹): 0.095; F000: 512.0; h,k,l_max: 12,12,16; N_ref. 4321; T_min, T_max: 0.918, 1.000; correction method = # reported T_Limits: T_min = 0.918T_max = 1.000; Abs_Corr = MULTI-SCAN; data completeness = 0.683; theta(max) = 29.120; R(reflections) = 0.0480(2649); wR₂(reflections) = 0.1297(4321); S = 1.024; N_par = 344.¹⁴

2-Chloro-4-methyl-dibenzo[b,h][1,6]naphthyridine (3i). Reaction time: 14 h; yield: 82%; yellow solid; mp: 226–230 °C; IR (KBr): ν 876 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 2.66 (s, 3H), 7.65–7.70 (m, 1H), 7.78 (s, 1H), 7.92–7.97 (m, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.38 (d, J = 9.0 Hz, 1H), 8.90 (s, 1H), 9.06 (s, 1H), 9.44 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 21.57, 119.43, 122.84, 126.65, 126.83, 127.18, 128.72, 129.79, 132.12, 132.41, 133.28, 137.41, 138.28, 140.34, 147.23, 150.37, 153.51; HRMS (ESI) exact mass calcd for C₁₇H₁₁ClN₂H: 279.0689 (M + H)⁺, found: 279.0680 (M + H)⁺.

5,12-Diaza-benzo[b]chrysene (3j)^15b. Reaction time: 16 h; yield 78%; brown solid; mp: 144–148 °C; IR (KBr): ν 746, 767 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.64–7.81 (m, 3H), 7.92–7.97 (m, 1H), 8.04 (d, J = 7.8 Hz, 1H), 8.12–8.17 (m, 2H), 8.43 (d, J = 8.7 Hz, 1H), 8.99 (s, 1H), 9.35–9.40 (m, 2H), 9.62 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 119.98, 121.24, 121.32, 122.20, 124.90, 126.52, 126.92, 127.78, 127.90, 128.24, 128.79, 129.90, 131.59, 132.03, 134.63, 137.33, 142.99, 147.73, 150.76, 152.94; HRMS (ESI) exact mass calcd for C₂₀H₁₂N₂H: 281.1078 (M + H)⁺, found: 281.1070 (M + H)⁺.

9-Methyl-dibenzo[b,h][1,6]naphthyridine (3k). Reaction time: 16 h; yield: 75%; orange solid; mp: 138–140 °C; IR (KBr): ν 803, 1023 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 2.62 (s, 3H), 7.75–7.84 (m, 4H), 8.17 (d, J = 7.2 Hz, 1H), 8.28 (d, J = 8.7 Hz, 1H), 8.74 (s, 1H), 9.30 (d, J = 6.9 Hz, 1H), 9.37 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 21.72, 113.14, 119.70, 124.15, 125.38, 127.00, 127.17, 127.63, 129.43, 130.43, 134.67, 136.13, 136.63, 145.81, 147.24, 149.18, 154.10; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂H: 245.1078 (M + H)⁺, found: 245.1070 (M + H)⁺.

10-Methyl-dibenzo[b,h][1,6]naphthyridine (3l). Reaction time: 16 h; yield: 78%; brown solid; mp: 168–170 °C; IR (KBr): ν 754, 1480, 1599 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 2.66 (s, 3H), 7.47 (d, J = 8.4 Hz, 1H), 7.76–7.84 (m, 2H), 7.97 (d, J = 8.4 Hz, 1H), 8.15–8.18 (m, 2H), 8.77 (s, 1H), 9.30 (d, J = 7.8 Hz, 1H), 9.34 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 22.25, 119.06, 124.19, 125.16, 127.43, 128.14, 128.26, 129.09, 129.32, 130.43, 134.48, 136.53, 142.66, 145.87, 147.73, 150.43, 154.00; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂H: 245.1078 (M + H)⁺, found: 245.1073 (M + H)⁺.

9-Methoxy-dibenzo[b,h][1,6]naphthyridine (3m)^15b. Reaction time: 15 h; yield: 80%; brown solid; mp: 134–138 °C; IR (KBr): ν 824, 1600 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 4.02 (s, 3H), 7.30 (s, 1H), 7.61 (d, J = 9.1 Hz, 1H), 7.77–7.83 (m, 2H), 8.18 (d, J = 7.8 Hz, 1H), 8.29 (d, J = 9.1 Hz, 1H), 8.73 (s, 1H), 9.29 (d, J = 7.8 Hz, 1H), 9.38 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 55.68, 104.27, 119.84, 123.90, 125.45, 126.40, 127.66, 128.17, 129.45, 130.14, 131.25, 134.94, 145.62, 146.00, 147.19, 153.85, 157.79; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂OH: 261.1028 (M + H)⁺, found: 261.1020 (M + H)⁺.

10-Methoxy-dibenzo[b,h][1,6]naphthyridine (3n). Reaction time: 15 h; yield: 82%; brown solid; mp: 172–174 °C; IR (KBr): ν 758, 1600 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 4.07 (s, 3H), 7.32 (dd, J = 9.3, 2.1 Hz, 1H), 7.64 (s, 1H), 7.74–7.79 (m, 1H), 7.83–7.87 (m, 1H), 7.98 (d, J = 9.3 Hz, 1H), 8.18 (d, J = 7.8 Hz, 1H), 8.77 (s, 1H), 9.29 (d, J = 7.8 Hz, 1H), 9.35 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 55.78, 106.31, 118.36, 121.44, 122.96, 124.15, 125.17, 127.41, 129.38, 129.83, 130.55, 136.66, 146.15, 148.22, 152.43, 153.88, 162.94; HRMS (ESI) exact mass calcd for C₁₇H₁₂N₂OH: 261.1028 (M + H)⁺, found: 261.1035 (M + H)⁺.

10-Chloro-dibenzo[b,h][1,6]naphthyridine (3o). Reaction time: 13 h; yield: 84%; white solid; mp: 182–184 °C; IR (KBr): ν 756, 1600 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 7.62 (d, J = 8.7 Hz, 1H), 7.77–7.82 (m, 1H), 7.86–7.91 (m, 1H), 8.07 (d, J = 8.7 Hz, 1H), 8.19 (d, J = 7.5 Hz, 1H), 8.41 (s, 1H), 8.86 (s, 1H), 9.30 (d, J = 8.1 Hz, 1H), 9.39 (s, 1H); ¹³C NMR (75 MHz, CDCl₃): δ 119.54, 124.38, 124.95, 125.32, 127.88, 127.94, 128.57, 129.59, 129.88, 131.08, 137.04, 138.16, 146.15, 148.66, 150.34, 153.80; HRMS (ESI) exact mass calcd for C₁₆H₉ClN₂H: 265.0532 (M + H)⁺, found: 265.0524 (M + H)⁺.

4-Chloro-10-methyl-dibenzo[b,h][1,6]naphthyridine (3p). Reaction time: 15 h; yield: 82%; yellow solid; mp: 238–240 °C; IR (KBr): ν 758, 1596, cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 2.68 (s, 3H), 7.52 (dd, J = 8.5, 1.0 Hz, 1H), 7.66–7.69 (m, 1H), 7.94 (dd, J = 7.5, 1.0 Hz, 1H), 8.01 (d, J = 8.5 Hz, 1H), 8.15 (s, 1H), 8.85 (s, 1H), 9.26 (dd, J = 8.0, 1.5 Hz, 1H), 9.48 (s, 1H); ¹³C NMR (125 MHz, CDCl₃): δ 22.39, 119.02, 123.20, 125.56, 127.21, 127.57, 128.34, 128.43, 129.69, 131.01, 133.66, 137.12, 142.24, 143.36, 147.42, 150.83, 154.70; HRMS (ESI) exact mass calcd for C₁₇H₁₁ClN₂H: 279.0689 (M + H)⁺, found: 279.0687 (M + H)⁺.

4-Chloro-10-methoxy-dibenzo[b,h][1,6]naphthyridine (3q). Reaction time: 14 h; yield: 84%; brown solid; mp: 210–214 °C; IR (KBr): ν 757, 1597 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 4.07 (s, 3H), 7.34 (dd, J = 9.0, 2.0 Hz, 1H), 7.61 (d, J = 1.5 Hz, 1H), 7.65–7.68 (m, 1H), 7.94 (d, J = 7.5 Hz, 1H), 7.98 (d, J = 9.5 Hz, 1H), 8.80 (s, 1H), 9.24 (d, J = 7.5 Hz, 1H), 9.45 (s, 1H); ¹³C NMR (125 MHz, CDCl₃): δ 55.84, 106.32, 118.21, 121.93, 123.14, 123.24, 127.03, 127.38, 129.89, 130.99, 133.66, 136.98, 142.48, 147.79, 152.71, 154.53, 163.25; HRMS (ESI) exact mass calcd for C₁₇H₁₁ClN₂OH: 295.0638 (M + H)⁺, found: 295.0638 (M + H)⁺.

Acknowledgements

JBS is thankful to CSIR for fellowship. KCB is thankful to DST for fellowship. TG is thankful to UGC for fellowship. RMS is thankful to CSIR for funding (02(0073)/12EMR-II). RMS is thankful to director, IISER Bhopal for HRMS spectra. Authors are thankful to Dr Syed S. Razi and Mr Sharad Kumar Asthana, BHU for their help in photophysical studies.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra. CCDC 1444965. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra00505e

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