CuSO₄–D-glucose, an inexpensive and eco-efficient catalytic system: direct access to diverse quinolines through modified Friedländer approach involving S_NAr/reduction/annulation cascade in one pot

Abstract

A highly efficient and scalable multicomponent domino reaction for the synthesis of functionalized/annulated quinolines is devised directly from 2-bromoaromatic aldehydes/ketones in H₂O–EtOH mixture for the first time. The key to this reaction is the use of an air-stable, eco-efficient and inexpensive CuSO₄–D-glucose catalyst system, which is able to catalyze multiple transformations in one pot. The approach is carbon-economic and relies on sequential S_NAr/reduction/Friedländer annulation steps, forming C–C and C–N bonds by cleavage of the Csp²–Br bond in a single synthetic operation. The reaction has a broad substrate scope and affords products in good to excellent yields.

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Introduction

Generation of structural diversity and molecular complexity from easily available and inexpensive starting materials in an operationally simple and one-pot, atom and cost-economic manner is one of the most promising challenges for synthetic chemists.¹ The core strategies to minimize the environmental impact of a reaction involve the use of greener solvents and recyclable, eco-friendly catalysts.^1e,f The copper-mediated transformations have emerged as a powerful method for the construction of C–C and C–heteroatom bonds because of their abundance, low cost, and eco-efficient nature.²

Nitrogen-containing heterocycles are omnipresent in natural products and pharmaceutical substances. Consequently, the development of methods for the introduction of nitrogen in simple organic compounds is an intense focus of modern research. Quinolines³ are present as a core structural unit in a wide range of pharmaceuticals and natural products.⁴ They have been recognized as a privileged structure in the field of natural alkaloids, material and medicinal chemistry, as well as in bio-organic/bio-organometallic processes.⁵ Furthermore, they show antimalarial, tumoricidal, antimycobacterial, antimicrobial, anticonvulsant, anti-inflammatory, anticardiovascular, antifungal, and HIV-1 integrase inhibitory activities.⁶ A number of quinoline derivatives have been successfully commercialized as drugs, such as Singulair, tafenoquine, Aldara, and hydroxychloroquine.⁷ Also, they are valuable synthons for the preparation of materials with unique electronic and optical properties.⁸

Due to their vast applications, several strategies for the synthesis of quinolines have been reported.⁹ The most common ones include Skraup,¹⁰ Friedländer,¹¹ Pfitzinger,¹² Conrad–Limpach,¹³ Combes¹⁴ and Doebner–von Miller¹⁵ synthesis. All these routes access quinoline synthesis through inter/intramolecular annulation of aniline or its derivatives with carbonyl compounds. The Friedländer reaction is the “evergreen” method of choice, and an array of conditional/structural modifications have been reported.¹⁶ Nevertheless, many existing methods are inefficient and require multiple steps, highly functionalized substrates and complicated operational procedures producing large quantities of waste. The most relevant limitation is the use of 2-aminobenzaldehyde as a substrate, which is highly prone to self-condensation.¹⁷ Therefore, 2-aminobenzylalcohols,^11b 2-nitrobenzaldehyde,^11c and 2-nitrobenzyl alcohols^16a are frequently utilized as 2-aminobenzaldehyde counterparts.^17b The privileged status of quinolines still demands more economical and eco-efficient strategies for their synthesis.^9a,18

To achieve this goal, two main approaches were taken into consideration: (1) the development of a suitable catalytic system and (2) the use of greener solvents instead of toxic organic solvents. The direct use of 2-bromoaromatic aldehydes/ketones with active methylene for the synthesis of quinolines has not been explored. Herein, we report an eco-efficient, one-pot protocol for the direct synthesis of diverse quinolines from commercially available 2-bromoaromatic aldehydes/ketones as a mimic of 2-aminobenzaldehyde in the presence of inexpensive CuSO₄–D-glucose catalyst system in the green water–ethanol solvent. This type of operationally simple and eco-friendly CuSO₄–D-glucose catalyzed one-pot S_NAr/reduction/heteroannulation cascade for the synthesis of quinolines has not been explored previously, to the best of our knowledge.

Results and discussion

With a view to constructing the quinoline framework, we selected 2-bromobenzaldehyde (1a) as a model substrate. In our initial study, the reaction of 1a (1.0 mmol) with sodium azide (2.0 mmol) and acetyl acetone (2a, 1.1 mmol) in the presence of Cu₂O (0.3 mmol) and proline (1.2 mmol) in DMSO at 90 °C in the open atmosphere afforded the desired product, 3-acetyl-2-methylquinoline 3aa, in 50% yield within 8 h (Table 1, entry 1). Encouraged by this result, we turned our attention to find the optimized reaction conditions by screening various catalysts, ligands and solvents. The results are listed in Table 1. The use of CuI (0.3 mmol) in place of Cu₂O in the above reaction afforded 3aa in 55% yield (Table 1, entry 2). Changing the solvent from DMSO to PEG-400 did not offer a better result (Table 1, entry 3). Acetic acid in place of proline was also found to be ineffective (Table 1, entry 4). Next, we assumed that the use of a base may improve the efficiency of this transformation.¹⁹ Consequently, the use of K₂CO₃ in the above reaction furnished the desired product 3aa, with 62% yield (Table 1, entry 5). Further screening of other Cu salts such as Cu(OAc)₂ and CuSO₄, separately, was found to be completely ineffective (Table 1, entries 6 and 7).

Table 1 Optimization studies for the synthesis of quinoline 3aa^a

Entry	Catalyst (mmol)	Ligand (mmol), base (mmol)	Solvent (5 mL)	Time (h)	Yield^b (%)
a Reaction conditions: 1a (1.0 mmol), 2a (1.1 mmol), NaN3 (2.0 mmol), CuSO4 (0.3 mmol), D-glucose (0.3 mmol), proline (0.2 mmol), KOH (1 mmol), H2O–EtOH (3 : 2, 5 mL), 90 °C.b Isolated pure yields.c n.r. = no reaction.d Partial conversion with several overlapping spots.
1	Cu2O (0.3)	Proline (1.2)	DMSO	8	50
2	CuI (0.3)	Proline (1.2)	DMSO	8	55
3	CuI (0.3)	Proline (1.2)	PEG-400	8	52
4	CuI (0.3)	Acetic acid (1.2)	DMSO	24	21
5	CuI (0.3)	Proline (1.2) + K2CO3 (1)	DMSO	8	62
6	Cu(OAc)2 (0.3)	Proline (1.2) + K2CO3 (1)	DMSO	24	n.r.^c
7	CuSO4 (0.3)	Proline (1.2) + K2CO3 (1)	DMSO	24	n.r.^c
8	CuSO4 (0.3) + Na–L-ascorbate (0.3)	Proline (1.2) + K2CO3 (1)	DMSO	8	69
9	CuSO4 (0.3) + Na–L-ascorbate (0.3)	Proline (0.2) + K2CO3 (1)	DMSO	24	21
10	CuSO4 (0.3) + Na–L-ascorbate (0.3)	Proline (0.2) + K2CO3 (1)	EtOH	6	82
11	CuSO4 (0.3) + D-glucose (0.3)	Proline (0.2) + K2CO3 (1)	EtOH	5	87
12	CuSO4 (0.3) + D-glucose (0.3)	Proline (0.2) + K2CO3 (1)	H2O	5	72
13	CuSO4 (0.3) + D-glucose (0.3)	Proline (0.2) + K2CO3 (1)	H2O + EtOH (3 : 2)	4	91
14	CuSO4 (0.3) + D-glucose (0.3)	Proline (0.2) + KOH (1)	H2O + EtOH (3 : 2)	3	95
15	CuSO4 (0.1) + D-glucose (0.1)	Proline (0.2) + KOH (1)	H2O + EtOH (3 : 2)	15	57
16	CuSO4 (0.3) + D-glucose (0.3)	Proline (0.2) + KOH (1)	PEG-400	5	—^d

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On the basis of the above observations, we thought to generate Cu(I) in situ by the reduction of highly economical CuSO₄ salt. The use of sodium L-ascorbate with CuSO₄ noticeably increased the yield of 3aa to 69% (Table 1, entry 8). The reaction did not proceed to completion when a lesser amount of proline (0.2 equiv.) was used under similar conditions (Table 1, entry 9). This may be due to the dual role of proline as ligand and a proton source. Therefore, DMSO was replaced with ethanol to provide the direct proton source. Notably, the use of EtOH as a solvent in the presence of 0.2 equiv. of proline increased the yield to 82% (Table 1, entry 10). We presume that this protocol undergoes copper-promoted, Ullmann-type coupling of 1a with NaN₃, followed by reduction to give 2-aminobenzaldehyde in situ. The subsequent reaction of 2-aminobenzaldehyde with acetyl acetone 2a via Friedländer annulation afforded the desired quinoline 3aa.

The success of this protocol prompted us to investigate the use of the reducing carbohydrate D-glucose. To our pleasure, the use of D-glucose in place of sodium L-ascorbate increased the yield to 87% (Table 1, entry 11).

In an attempt to find a green solvent, the above reaction was performed in water. Although the desired product 3aa was obtained with 72% yield, the initial substrates were not completely soluble in water and remained unconsumed (Table 1, entry 12). We deemed to add ethanol to boost the yield of the reaction. After several attempts, a better result was obtained by carrying out the reaction in water–ethanol (3 : 2) mixture (Table 1, entry 13). We envisioned that the use of a stronger base such as KOH in place of K₂CO₃ may further improve the efficiency of the reaction by promoting dehydrative cyclization. As expected, the use of KOH increased the yield from 91% to 95% as well as reducing the reaction time from 4 h to 3 h (Table 1, entry 14). Upon lowering of the catalytic loading, the conversion was drastically diminished (Table 1, entry 15). Finally, when the model reaction was carried out in PEG-400 at 90 °C, only partial conversion with several overlapping spots was observed (Table 1, entry 16). Thus, the optimum reaction conditions for the synthesis of quinoline 3aa were achieved by employing 1a (1 mmol), NaN₃ (2 mmol), 2a (1.1 mmol), CuSO₄ (0.3 mmol), D-glucose (0.3 mmol), proline (0.2 mmol) and KOH (1 mmol) in water–ethanol (3 : 2) mixture at 90 °C.

Under the optimal reaction conditions, the protocol scope and generality for the direct construction of quinolines (3) was explored (Table 2). The one-pot cascade process serves as a general approach to access valuable substituted/annulated quinolines with excellent yields (86–95%) and a broad substrate scope. 2-Bromobenzaldehydes (1a–b) and 2-bromobenzophenone (1c) reacted smoothly with both acyclic (2a–b) and cyclic (2c–d) 1,3-diketones, affording the corresponding quinolines (3) in excellent yields.

Table 2 Reaction of 2-bromobenzaldehydes/2-bromobenzophenone with 1,3-diketones

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To illustrate the broad synthetic utility and generality of our developed one-pot domino methodology, we further treated 2-bromoaromatic aldehydes/ketone (1a–c) with various monocyclic and bicyclic ketones (2e–g) separately under the above optimized conditions. Both mono and bicyclic ketones were tolerated well and furnished the corresponding quinolines (3) with 76–86% yield (Table 3). Notably, the bicyclic ketone 2g also worked efficiently and afforded the tetracyclic quinoline 3ag with 79% yield. It seems that the ring size of the cyclic ketones has no effect on the tandem process.

Table 3 Reaction of 2-bromobenzaldehydes/2-bromobenzophenone with cyclic ketones

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After the successful synthesis of 2,3-disubstituted/annulated quinolines, we turned our attention toward the synthesis of 2-substituted quinolines. Consequently, we utilized various acetophenones (2h–o) and heteroaromatic ketones (2p–r) under the previously described one-pot optimized conditions. The workup of the reactions afforded the desired 2-substituted quinolines (3) with good yields. Notably, a series of substituted acetophenones groups on the phenyl ring, such as o-Cl, m-Cl, p-Cl, p-Me, m-OMe, p-OMe, are well tolerated, and the corresponding 2-substituted quinolines (3ah–3an) were obtained with 76–85% yield (Table 4). The protocol worked nicely with both electron-donating and electron-withdrawing groups at ortho-, meta-, and para-positions of the phenyl ring. The bulky naphthyl ethanone (2o) also reacted under similar conditions to produce quinoline 3ao in moderate yield. In addition, the reaction of propiophenone (2s) and butyrophenone (2t) separately with 2-bromobenzaldehyde (1a) was successfully performed to afford the respective quinolines 3as and 3at with good yields. The structure of all the compounds showed full agreement with spectroscopic data and previous reports.^9a,20

Table 4 Reaction of 2-bromobenzaldehyde/2-bromobenzophenone with acyclic ketones

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To demonstrate the usefulness of this novel one-pot domino protocol, a gram-scale experiment was carried out under the standard reaction conditions. The reaction of 2-bromobenzaldehyde 1a (4 mL, 20 mmol) proceeded smoothly, providing 6.76 g of product 3aa (92%), which is comparable to the small-scale experiment. Thus, this new methodology could be useful for the facile synthesis of quinoline scaffolds on an industrial scale. The use of inexpensive and easily prepared CuSO₄–D-glucose as an ideal catalytic system offers an attractive prospect in terms of industrial applications and sustainable development.

Based on the entire experimental outcomes, a tentative mechanism is proposed in Scheme 1. Initially, Cu(I) (generated in situ by the reduction of CuSO₄ in presence of D-glucose, base and proline) undergoes oxidative addition with substrate 1 to give copper complex A. The nucleophilic substitution of Br with sodium azide gives the azido Cu complex B followed by reductive elimination to give complex C, which readily converts to ortho-aminoaldehyde/ketone D under the reaction conditions. Intermediate D undergoes dehydrative coupling with ketone 2 to afford intermediate E followed by base-catalyzed dehydrative cyclocondensation to produce the desired quinoline 3.

Scheme 1 Plausible mechanism for the synthesis of quinoline 3.

Conclusions

In summary, we have successfully designed and developed an operationally simple, highly efficient, one-pot, practical and convenient method for the synthesis of diverse quinolines directly from 2-bromobenzaldehydes/2-bromobenzophenone. The key features of this novel method are the inexpensively and easily prepared, eco-efficient CuSO₄–D-glucose catalyst system and the green aqueous ethanol solvent, which are promising synthetic applications. The scope and diversity of the tolerated substrates in this work is rather very broad in comparison to the reported ones. The salient features of this domino protocol are its methodical simplicity, structural diversity, perfect carbon-economy, high product yields, readily available substrates and the formation of three new bonds (one C–C and two C–N) and one ring in a single operation. In addition, the present one-pot process is amenable to gram-scale synthesis. Further investigations for the synthetic utility of this catalyst system in the synthesis of different heterocyclic rings are currently underway in our laboratory.

Experimental section

General experimental details

¹H and ¹³C NMR spectra were recorded at 300 and 75 MHz, respectively. Chemical shift (δ) values are given in parts per million (ppm) with reference to tetramethylsilane (TMS) as the internal standard. Coupling constant (J) values are given in Hertz (Hz). The IR spectra were recorded on a Varian 3100 FT-IR spectrophotometer. Melting points were determined with Buchi B-540 melting point apparatus and are uncorrected. Commercially obtained reagents were used after further purification as needed. All the reactions were monitored by TLC with silica gel-coated plates. Column chromatography was carried out whenever needed, using silica gel of 100/200 mesh. A mixture of hexane–ethyl acetate in appropriate proportion (determined by TLC analysis) was used as eluent.

General procedure for the synthesis of compound 3

A mixture of 2-bromobenzaldehyde/2-bromoacetophenone 1 (1 mmol), NaN₃ (2 mmol) and cyclic/acyclic ketones 2 (1.1 mmol) in H₂O + EtOH (3 : 2, 5 mL) was placed in a 50 mL round-bottom flask. To a stirring solution of the above mixture was added CuSO₄ (0.3 mmol), D-glucose (0.3 mmol), proline (0.2 mmol) and KOH (1 mmol). The reaction mixture was allowed to stir at 90 °C for 3–10 h. After completion of the reaction (monitored on TLC), the solvent was removed under reduced pressure and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulphate and filtered, and the solvent was removed under reduced pressure. The crude residue thus obtained was purified by column chromatography to give the desired quinolines (3).

3-Acetyl-2-methyl quinoline (3aa)^20a. Pale yellow solid, mp 74–75 °C; IR (KBr) cm⁻¹: 3053, 1788, 1624, 1579, 1456, 818; ¹H NMR (300 MHz, CDCl₃) δ 8.48 (s, 1H, ArH), 8.05 (d, J = 8.4 Hz, 1H, ArH), 7.87–7.76 (m, 2H, ArH), 7.57–7.52 (m, 1H, ArH), 2.91 (s, 3H, COCH₃), 2.72 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 199.9, 157.5, 138.2, 138.1, 131.6, 131.1, 128.5, 128.2, 126.6, 125.5, 29.2, 25.6.

Phenyl(2-phenylquinolin-3-yl)methanone (3ab)^20b. Yellow solid, mp 135–137 °C; IR (KBr) cm⁻¹: 3163, 2960, 1756, 1684, 1562; ¹H NMR (300 MHz, CDCl₃) δ 8.23–8.15 (m, 5H, ArH), 8.00 (d, J = 6.9 Hz, 1H, ArH), 7.89–7.81 (m, 2H, ArH), 7.75–7.70 (m, 1H, ArH), 7.55–7.43 (m, 6H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 175.7, 157.3, 148.2, 139.6 (2C), 136.7, 132.4, 129.6, 129.2 (2C), 128.8 (3C), 128.6 (3C), 127.4 (2C), 127.1 (2C), 126.2, 118.9.

3,4-Dihydroacridin-1(2H)-one (3ac)^20a. White solid, mp 103–105 °C; IR (KBr) cm⁻¹: 3463, 2926, 1737, 1452, 1230, 835; ¹H NMR (300 MHz, CDCl₃) δ 8.85 (s, 1H, ArH), 8.06 (d, J = 8.4 Hz, 1H, ArH), 7.94 (d, J = 8.1 Hz, 1H, ArH), 7.83–7.78 (m, 1H, ArH), 7.57 (t, J = 7.2 Hz, 1H, ArH), 3.34 (t, J = 6.0 Hz, 2H, CH₂), 2.82 (t, J = 6.0 Hz, 2H, CH₂), 2.32 (dd, J₁ = 6.0 Hz, J₂ = 12.6 Hz, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 197.8, 161.9, 137.1, 132.3, 129.7, 128.4, 126.7, 126.6, 126.2, 39.0, 33.3, 21.7.

3,3-Dimethyl-3,4-dihydroacridin-1(2H)-one (3ad)^20a. White solid, mp 116–118 °C; IR (KBr) cm⁻¹: 3062, 1768, 1594, 1488, 1231; ¹H NMR (300 MHz, CDCl₃) δ 8.82 (s, 1H, ArH), 8.06 (d, J = 8.7 Hz, 1H, ArH), 7.94 (d, J = 8.1 Hz, 1H, ArH), 7.82–7.77 (m, 1H, ArH), 7.57–7.52 (m, 1H, ArH), 3.20 (s, 2H, CH₂), 2.65 (s, 2H, CH₂), 1.15 (s, 6H, 2 × CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 197.9, 160.7, 149.9, 136.4, 132.1, 129.7, 128.5, 126.6 (2C), 125.2, 52.4, 47.1, 32.7, 28.3 (2C).

7-Methoxy-3,3-dimethyl-3,4-dihydroacridin-1(2H)-one (3bd)^20c. Yellow solid, mp 98–100 °C; IR (KBr) cm⁻¹: 3062, 1768, 1594, 1488, 1231; ¹H NMR (300 MHz, CDCl₃) δ 8.73 (s, 1H, ArH), 7.97 (d, J = 9.0 Hz, 1H, ArH), 7.47–7.43 (m, 1H, ArH), 7.167 (s, 1H, ArH), 3.93 (s, 3H, OCH₃), 3.16 (s, 2H, CH₂), 2.63 (s, 2H, CH₂), 1.14 (s, 6H, 2 × CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 198.1, 158.2, 157.7, 146.1, 135.0, 129.8 (2C), 127.7, 125.3, 106.3, 55.6, 52.4, 46.7, 32.8, 28.3 (2C).

3-Acetyl-2-methyl-4-phenyl-quinoline (3ca)^20d. Yellow solid, mp 112–114 °C; IR (KBr) cm⁻¹: 3053, 1788, 1624, 1579, 1456, 818; ¹H NMR (300 MHz, CDCl₃) δ 8.08 (d, J = 8.4 Hz, 1H, ArH), 7.72–7.67 (m, 1H, ArH), 7.62 (d, J = 8.4 Hz, 1H, ArH), 7.49–7.44 (m, 3H, ArH), 7.42–7.34 (m, 3H, ArH), 2.70 (s, 3H, CH₃), 2.00 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 205.5, 153.3, 147.3, 143.7, 135.0, 134.6, 129.9, 129.8 (2C), 128.8, 128.7, 128.5 (2C), 126.3, 126.0, 124.8, 31.8, 23.7.

9-Phenyl-3,4-dihydroacridin-1(2H)-one (3cc)^20d. Pale yellow solid, mp 153–156 °C; IR (KBr) cm⁻¹: 3407, 3048, 2924, 1737, 1498, 1230, 749; ¹H NMR (300 MHz, CDCl₃) δ 8.08 (d, J = 8.4 Hz, 1H, ArH), 7.78 (m, 1H, ArH), 7.50–7.37 (m, 5H, ArH), 7.19–7.16 (m, 2H, ArH), 3.40 (t, J = 6.3 Hz, 2H, CH₂), 2.72 (t, J = 6.3 Hz, 2H, CH₂), 2.29 (dd, J₁ = 6.6 Hz, J₂ = 12.6 Hz, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 197.9, 162.2, 151.4, 148.5, 137.5, 131.7, 128.4 (2C), 128.1, 128.0 (2C), 127.9, 127.5 (2C), 126.4, 123.8, 40.6, 34.5, 21.3.

2,3-Dihydro-1H-cyclopenta[b]quinoline (3ae)^20a. White solid, mp 55–57 °C; IR (KBr) cm⁻¹: 3053, 1646, 1562, 1212; ¹H NMR (300 MHz, CDCl₃) δ 8.02 (d, J = 8.4 Hz, 1H, ArH), 7.70 (s, 1H, ArH), 7.67–7.64 (m, 1H, ArH), 7.60–7.55 (m, 1H, ArH), 7.43–7.38 (m, 1H, ArH), 3.14 (t, J = 7.5 Hz, 2H, CH₂), 3.02 (t, J = 7.2 Hz, 2H, CH₂), 2.19–2.11 (dd, J₁ = 7.5 Hz, J₂ = 15.0 Hz, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 157.6, 147.2, 135.3, 130.0, 128.3, 128.2, 128.0, 127.1, 125.2, 34.3, 30.2, 23.3.

1,2,3,4-Tetrahydroacridine (3af)^20a,e. White solid, mp 85–87 °C; IR (KBr) cm⁻¹: 3058, 1624, 1557, 1453, 1214; ¹H NMR (300 MHz, CDCl₃) δ 7.97 (d, J = 8.4 Hz, 1H, ArH), 7.70 (s, 1H, ArH), 7.67–7.64 (m, 1H, ArH), 7.60–7.55 (m, 1H, ArH), 7.42–7.37 (m, 1H, ArH), 3.13 (t, J = 6.3 Hz, 2H, CH₂), 2.96 (t, J = 6.3 Hz, 2H, CH₂), 1.99–1.95 (m, 2H, CH₂), 1.88–1.84 (m, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 159.1, 146.4, 134.8, 130.8, 128.3, 128.1, 127.0, 126.7, 125.3, 33.4, 29.1, 23.1, 22.7.

5,6-Dihydrobenzo[a]acridine (3ag)^20f. Yellow solid, mp 63–65 °C; IR (KBr) cm⁻¹: 3417, 2929, 1498, 1278, 1033, 789; ¹H NMR (300 MHz, CDCl₃) δ 8.58 (d, J = 7.5 Hz, 1H, ArH), 8.13 (d, J = 8.4 Hz, 1H, ArH), 7.84 (s, 1H, ArH), 7.69–7.59 (m, 2H, ArH), 7.45–7.31 (m, 3H, ArH), 7.24 (d, J = 7.2 Hz, 1H, ArH), 3.08–3.04 (m, 2H, CH₂), 2.97–2.93 (m, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 153.2, 147.5, 139.3, 134.6, 133.6, 130.4, 129.5, 129.3, 128.5, 127.8, 127.7, 127.2, 126.8, 126.0, 125.9, 28.7, 28.3.

7-Methoxy-2,3-dihydro-1H-cyclopenta[b]quinoline (3be)^20g. White solid, mp 97–99 °C; IR (KBr) cm⁻¹: 3407, 3048, 2924, 1595, 1498, 1230, 749; ¹H NMR (300 MHz, CDCl₃) δ 7.91 (d, J = 9.3 Hz, 1H, ArH), 7.77 (s, 1H, ArH), 7.28–7.24 (m, 1H, ArH), 7.00 (d, J = 2.7 Hz, 1H, ArH), 3.90 (s, 3H, OCH₃), 3.24 (t, J = 7.5 Hz, 2H, CH₂), 3.14–3.02 (m, 4H, 2 × CH₂), 2.23–2.13 (m, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 165.2, 157.0, 143.3, 135.9, 129.7, 129.3, 128.2, 120.4, 105.5, 55.4, 34.2, 30.5, 23.6.

9-Phenyl-2,3-diydro-1-cyclopenta[b]quinoline (3ce)^20d. Yellow solid, mp 133–135 °C; IR (KBr) cm⁻¹: 3053, 1625, 1586, 1230, 1033, 836; ¹H NMR (300 MHz, CDCl₃) δ 8.09 (d, J = 8.4 Hz, 1H, ArH), 7.63 (m, 2H, ArH), 7.51–7.45 (m, 3H, ArH), 7.37–7.34 (m, 3H, ArH), 3.24 (t, J = 7.5 Hz, 2H, CH₂), 2.90 (t, J = 7.2 Hz, 2H, CH₂), 2.21–2.11 (m, 2H, CH₂); ¹³C NMR (75 MHz, CDCl₃) δ 167.3, 147.7, 142.8, 136.7, 133.6, 129.2 (2C), 128.6, 128.4, 128.2, 127.9 (2C), 126.2, 125.6, 125.5, 35.1, 30.3, 23.5.

2-Phenylquinoline (3ah)^20e,f. White solid, mp 85–87 °C; IR (KBr) cm⁻¹: 3056, 1612, 1598, 1557, 1478; ¹H NMR (300 MHz, CDCl₃) δ 8.21–8.14 (m, 3H, ArH), 7.88–7.80 (m, 2H, ArH), 7.74–7.69 (m, 1H, ArH), 7.55–7.43 (m, 5H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 157.3, 148.2, 139.6, 129.6, 129.2 (2C), 128.8 (2C), 127.5 (2C), 127.4, 127.1, 126.2, 118.9.

2-(2-Chlorophenyl)quinoline (3ai)^9a. White solid, mp 72–75 °C; IR (KBr) cm⁻¹: 3063, 1614, 1574, 1512, 1423; ¹H NMR (300 MHz, CDCl₃) δ 8.20–8.17 (m, 2H, ArH), 8.13–8.08 (m, 2H, ArH), 7.81–7.69 (m, 2H, ArH), 7.54–7.45 (m, 3H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 155.9, 148.1, 137.9, 136.9, 135.5, 129.9, 129.8, 128.9 (2C), 128.7 (2C), 127.4, 127.1, 126.4, 118.6.

2-(3-Chlorophenyl)quinoline (3aj)^20h. White solid, mp 65–67 °C; IR (KBr) cm⁻¹: 3025, 2915, 1664, 1574, 1497, 1431, 815; ¹H NMR (300 MHz, CDCl₃) δ 8.24–8.16 (m, 3H, ArH), 8.03–7.97 (m, 1H, ArH), 7.85–7.71 (m, 3H, ArH), 7.56–7.51 (m, 2H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 155.7, 137.0, 134.9, 132.6, 130.8, 130.2, 129.9, 129.7, 129.3, 128.5, 127.7, 127.4, 126.6, 125.6, 118.6.

2-(4-Chlorophenyl)quinoline (3ak)^9a. White solid, mp 110–113 °C; IR (KBr) cm⁻¹: 3065, 1610, 1553, 1525, 1412; ¹H NMR (300 MHz, CDCl₃) δ 8.20–8.08 (m, 4H, ArH), 7.81–7.69 (m, 3H, ArH), 7.54–7.46 (3H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 155.9, 148.1, 138.0, 136.9, 135.5, 129.7, 129.6, 128.9 (2C), 128.7 (2C), 127.4, 127.1, 126.4, 118.4.

2-p-Tolylquinoline (3al)^20f. White solid, mp 80–82 °C; IR (KBr) cm⁻¹: 3422, 2915, 1668, 1618, 1596, 1497, 815, 788; ¹H NMR (300 MHz, CDCl₃) δ 8.15 (d, J = 8.4 Hz, 2H, ArH), 8.06 (d, J = 8.1 Hz, 2H, ArH), 7.83–7.68 (m, 3H, ArH), 7.49–7.47 (m, 1H, ArH), 7.32 (d, J = 7.8 Hz, 2H, ArH), 2.41 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 157.2, 148.2, 139.3, 136.8, 136.5, 129.6 (2C), 129.4 (2C), 127.3 (3C), 127.0, 126.0, 118.7, 21.2.

2-(3-Methoxyphenyl)quinoline (3am)^20h. Yellow oil, IR (neat) cm⁻¹: 3152, 1604, 1563, 1498; ¹H NMR (300 MHz, CDCl₃) δ 8.17 (d, J = 8.4 Hz, 1H, ArH), 8.10 (d, J = 8.7 Hz, 1H, ArH), 7.78–7.65 (m, 5H, ArH), 7.47–7.35 (m, 2H, ArH), 6.99 (d, J = 8.1 Hz, 1H, ArH), 3.86 (s, 3H, OCH₃); ¹³C NMR (75 MHz, CDCl₃) δ 160.0, 156.8, 148.0, 140.9, 136.5, 129.6, 129.5, 129.4, 127.3, 127.1, 126.1, 119.8, 118.8, 115.2, 112.6, 55.2.

2-(4-Methoxyphenyl)quinoline (3an)^20f. White solid, mp 117–120 °C; IR (KBr) cm⁻¹: 3039, 2921, 2840, 1604, 1499, 1251, 1029, 818; ¹H NMR (300 MHz, CDCl₃) δ 8.14–8.11 (m, 4H, ArH), 7.80–7.75 (m, 2H, ArH), 7.71–7.65 (m, 1H, ArH), 7.49–7.44 (m, 1H, ArH), 7.03 (d, J = 8.7 Hz, 2H, ArH), 3.85 (s, 3H, OCH₃); ¹³C NMR (75 MHz, CDCl₃) δ 160.7, 156.8, 148.2, 136.5, 132.1, 129.5, 129.4, 128.8, 127.3, 126.8, 125.8, 118.4, 114.1 (2C), 55.3.

2-(Naphthalen-2-yl)quinoline (3ao)^20f. White solid, mp 163–165 °C; IR (KBr) cm⁻¹: 3058, 1622, 1567, 1256; ¹H NMR (300 MHz, CDCl₃) δ 8.59 (s, 1H, ArH), 8.37 (d, J = 8.7 Hz, 1H, ArH), 8.22 (d, J = 8.4 Hz, 2H, ArH), 8.00–7.96 (m, 3H, ArH), 7.89–7.86 (m, 1H, ArH), 7.82 (d, J = 8.1 Hz, 1H, ArH), 7.75–7.70 (m, 1H, ArH), 7.53–7.49 (m, 2H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 157.1, 148.3, 136.7, 133.8, 133.4, 129.6, 128.9, 128.7 (2C), 128.5, 127.6, 127.4, 127.2, 127.1, 126.6, 126.2 (2C), 125.0, 119.0.

2-(Furan-2-yl)quinoline (3ap)^20f. White solid, mp 90–92 °C; IR (KBr) cm⁻¹: 3152, 1618, 1523, 1489; ¹H NMR (300 MHz, CDCl₃) δ 8.15–8.12 (m, 2H, ArH), 7.81–7.61 (m, 4H, ArH), 7.47 (t, J = 7.5 Hz, 1H, ArH), 7.22–7.21 (m, 1H, ArH), 6.57 (bs, 1H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 153.6, 148.9, 148.0, 144.0, 136.6, 129.8, 129.3, 127.5, 127.1, 126.1, 117.4, 112.1, 110.0.

2-(Thiophen-2-yl)quinoline (3aq)^20f. White solid, mp 125–128 °C; IR (KBr) cm⁻¹: 3101, 3054, 1624, 1578, 1223; ¹H NMR (300 MHz, CDCl₃) δ 8.11–8.06 (m, 2H, ArH), 7.77–7.65 (m, 4H, ArH), 7.48–7.43 (m, 2H, ArH), 7.15–7.12 (m, 1H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 152.2, 148.0, 145.3, 136.5, 129.7, 129.2, 128.5, 128.0, 127.4, 127.1, 126.0, 125.7, 117.5.

2-(Pyridin-2-yl)quinoline (3ar)²⁰ⁱ. White solid, mp 93–95 °C; IR (KBr) cm⁻¹: 3059, 2924, 1599, 1095, 787; ¹H NMR (300 MHz, CDCl₃) δ 8.51 (d, J = 7.8 Hz, 1H, ArH), 8.25 (d, J = 8.7 Hz, 1H, ArH), 8.18 (d, J = 8.4 Hz, 1H, ArH), 7.86–7.71 (m, 4H, ArH), 7.56–7.47 (m, 3H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 154.5, 150.0, 148.6, 148.2, 137.0 (2C), 134.8, 129.9, 129.6, 127.4, 127.2, 126.7 (2C), 118.4.

2,4-Diphenylquinoline (3ch)^16b. White solid, mp 112–115 °C; IR (KBr) cm⁻¹: 3423, 3086, 2955, 1589, 1095, 846; ¹H NMR (300 MHz, CDCl₃) δ 7.81 (d, J = 7.2 Hz, 4H, ArH), 7.67–7.56 (m, 4H, ArH), 7.51–7.38 (m 5H, ArH), 7.35–7.31 (m, 2H, ArH); ¹³C NMR (75 MHz, CDCl₃) δ 163.1, 140.5, 137.5, 136.2, 136.0, 133.6, 133.0, 132.3, 131.8, 131.0, 130.0, 129.9, 129.0, 128.8, 128.5, 128.2, 128.1, 127.1, 119.4, 118.5, 118.5.

3-Methyl-2-phenylquinoline (3as)^20e,f. Yellow oil; IR (neat) cm⁻¹: 3052, 1618, 1553, 1431, 1097, 756; ¹H NMR (300 MHz, CDCl₃) δ 8.13 (d, J = 8.4 Hz, 1H, ArH), 7.96 (s, 1H, ArH), 7.74 (d, J = 8.1 Hz, 1H, ArH), 7.65–7.56 (m, 3H, ArH), 7.46–7.40 (m, 4H, ArH), 2.43 (s, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 160.4, 146.5, 140.8, 136.6, 129.2, 129.0, 128.7 (2C), 128.6, 128.1 (2C), 128.0, 127.5, 126.6, 126.2, 20.5.

3-Ethyl-2-phenylquinoline (3at)^20j. Yellow oil; IR (neat) cm⁻¹: 3048, 2924, 1595, 1432, 749; ¹H NMR (300 MHz, CDCl₃) δ 8.14 (d, J = 8.4 Hz, 1H, ArH), 8.01 (s, 1H, ArH), 7.79 (d, J = 7.8 Hz, 1H, ArH), 7.66–7.61 (m, 1H, ArH), 7.54–7.52 (m, 2H, ArH), 7.48–7.41 (m, 4H, ArH), 2.81–2.73 (m, 2H, CH₂), 1.19 (t, J = 7.8 Hz, 3H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 160.5, 146.2, 140.8, 135.1, 134.8, 129.1, 128.7, 128.6, 128.1, 127.9, 127.6, 126.8, 126.2, 25.9, 14.6.

Acknowledgements

We gratefully acknowledge the financial support from the Science and Engineering Research Board (SB/S1/OC-30/2013) and the University Grant Commission, New Delhi, India.

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Footnote

† Electronic supplementary information (ESI) available: Elaborate reaction procedure, characterization data, scanned spectra of all the products. See DOI: 10.1039/c4ra14138e

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