Copper-catalyzed synthesis of quinoline derivatives via tandem Knoevenagel condensation, amination and cyclization

Abstract

A novel regioselective synthesis of 2-aminoquinolines and 2-arylquinoline-3-carbonitriles is described via copper-mediated tandem reaction. Formation of substituted quinolines involves Knoevenagel condensation of ortho-bromobenzaldehyde with active methylene nitriles followed by copper-catalyzed reductive amination and intramolecular cyclization.

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Introduction

The quinoline skeleton is one of the most prevalent motifs, found in many drugs, natural products and pharmacologically active substances.¹ Compounds with this motif have been found to possess a broad range of biological activities such as anticancer,² antifungal,³ antimalarial,⁴ antituberculosis,⁵ antiprotozoal,⁶ antiinflammatory,⁷ antineoplastic,⁸ and inhibition of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER-2) kinases.⁹ Functionalized quinolines are also used as dyestuffs,¹⁰ asymmetric catalysts,¹¹ ligands for transition metal complexes and for the preparation of nano- and mesostructures with improved electronic and photonic properties.¹² Some promising compounds with quinoline motif are shown in Fig. 1.

Fig. 1 Some promising quinoline derivatives.

Generally, quinoline and its derivatives are prepared by conventional methods including Friedländer, Pfitzinger, Doebner–von Miller, Skraup, Combes and Conrad–Limpach reactions.¹³ In past, these reactions have been successfully employed for quinoline synthesis but they require stoichiometric amounts of acidic reagents and are often performed under harsh conditions. Moreover, use of harsh reaction conditions and highly reactive acid catalysts restrict involvement of functionally substituted substrates for synthesis of corresponding quinolines. In recent years, several approaches based on tandem reactions, transition metal catalysts and alternative starting materials have been developed for mild and efficient syntheses of quinolines.¹⁴ For example, Li et al. have developed a copper-catalyzed synthesis of quinolines from ortho-acylanilines and alkenyl iodides.¹⁵ Yu and co-workers developed synthesis of quinolines from 2-aminobenzylamine and ketones via copper-catalyzed C–N bond cleavage.¹⁶ Consisting CuI and a secondary amine, Patil group developed a co-operative catalytic system for the synthesis of 2-substituted quinolines by utilizing 2-aminobenzaldehydes and terminal alkynes.¹⁷ In particular, 2-aminoquinolines are important target molecules because of their sub-nanomolar potency for BACE inhibition¹⁸ and selective neuronal nitric oxide synthase (nNOS) inhibition activities.¹⁹ Only a handful reports are available for synthesis of 2-aminoquinoline derivatives.²⁰ Tomioka et al. have reported one-pot synthesis of 2-aminoquinolines from 2-nitrobenzaldehydes and acetonitrile via stereoselective olefination followed by reductive cyclization.^20a Jiang group have synthesized 2-aminoquinolines by Pd-catalyzed reactions of gem-dibromovinylanilines and tert-butyl isocyanide.^20b,20c Liu et al. have utilized 4-halo-2-aminoquinolines in a Pd-catalyzed intermolecular aerobic oxidative cyclization of 2-ethynylanilines with isocyanide to prepare 2-aminoquinolines.^20d Owing to potential applications in various fields, quinolines continue to attract the attention of scientists from different areas, and the development of new synthetic methods for quinolines are still of great interest.

Furthermore, the direct amination of aryl halides using NaN₃ or TMSN₃ as the amino source in the presence of copper or copper salt has been reported.²¹ Trapping of the intermediate azide or amine of this copper catalyzed reductive amination have resulted in the synthesis of bioactive heterocycles such as quinolones, 3-aminoquinolines, 3-aminocoumarines, tetracyclic indoloindol-3-ones, pseudo-indoxyl derivatives, indazole and 2-aroylindoles.²² As a part of our continuous efforts in the development of new synthetic methods for heterocyclic compounds by employing C–C/C–N coupling reactions,²³ herein we report our results on one-pot copper-catalyzed regioselective synthesis of 2-aminoquinolines and 2-arylquinoline-3-carbonitriles via tandem reactions involving 2-bromobenzaldehydes, active methylene nitriles and sodium azide (Scheme 1).

Scheme 1 Synthesis of 2-aminoquinolines and 2-arylquinoline-3-carbonitriles.

Results and discussion

Our initial study began with the reaction of 2-bromobenzaldehyde (1a) with ethyl cyanoacetate (2a) and sodium azide in the presence of CuI (10 mol%), L-proline (20 mol%), K₂CO₃ (2.5 equiv.) in N,N′-dimethylformamide (DMF) at 150 °C under air atmosphere for 3 h. Gratifyingly, ethyl 2-aminoquinoline-3-carboxylate (4aa) was isolated in 35% yield (entry 1). The structure of 4aa was characterized by various spectroscopic techniques such as IR, NMR and mass spectrometry. In IR spectrum of 4aa, strong peaks at 3410 and 1697 cm⁻¹ are indicative of –NH₂ and –C=O functionalities, respectively. In ¹H NMR spectrum, characteristic singlets at δ 8.77 and δ 7.26 (broad) for C₄–H and NH₂ protons were observed. The carbonyl carbon of CO₂Et appeared at δ 166.5 along with all other expected peaks in ¹³C NMR spectrum of 4aa. Further, the structure was ascertained by HRMS analysis of 4aa which showed a molecular ion C₁₂H₁₃N₂O₂⁺ [M + H]⁺ peak at m/z 217.0976 in agreement with the calculated mass 217.0972.

To further improve the yield of tandem product 4aa, various experimental conditions were screened by varying copper catalysts, ligands, bases and solvents (Table 1). Firstly, screening of various copper salts such as CuI, CuCl₂, CuBr, Cu(OAc)₂·H₂O, CuOTf and CuSO₄ revealed that CuI was the best catalyst for this transformation giving highest yield of 4aa (Table 1, entries 1–6). Further investigations on the effect of catalyst loading suggested that 20 mol% CuI afforded 4aa in highest yield (55%) (Table 1, entries 1, 7 and 8). Among various bases (K₂CO₃, K₃PO₄, tBuOK, Cs₂CO₃, Na₂CO₃, NaOMe, Et₃N and DBU) examined (Table 1, entries 7, 9–16), K₂CO₃ was found to be the most suitable base. In case of triethylamine, the reaction exclusively led to Knoevenagel adduct (Table 1, entry 14). Reactions in different solvents namely DMSO, N,N-dimethylacetamide (DMA), toluene, N-methyl-2-pyrrolidone (NMP), 1,4-dioxane and PEG-400 (Table 1, entries 16–21) revealed DMSO as a the solvent of choice for this reaction. When the reaction was performed in toluene at 120 °C only Knoevenagel adduct was obtained in 45% yield (Table 1, entry 20). Finally, by screening of different ligands (Table 1, entries 16, 21–25), L-proline was found to be the most effective ligand. The reaction was stopped at the Knoevenagel adduct in the absence of catalyst (Table 1, entry 26) and yield of desired product 4aa was diminished in the absence of L-proline (Table 1, entry 27).

Table 1 Optimization of reaction conditions^a

Entry	Catalyst (mol%)	Ligand (mol%)	Base (2.5 equiv.)	Solvent	Yield^b (%)
a Reaction conditions: 1a (0.54 mmol), 2a (0.65 mmol) NaN3 (3) (0.81 mmol), catalyst, ligand, base (2.5 equiv.), 150 °C, air atmosphere, 3 h.b Isolated yields.c Reaction time 12 h, only Knoevenagel adduct 6.d Knoevenagel adduct 6 (120 °C, 45%).e 1,10-Phen = 1,10-phenanthroline.f 8-HQ = 8-hydroxyquinoline.
1	CuI (10)	L-Proline (20)	K2CO3	DMF	35
2	CuCl2 (10)	L-Proline (20)	K2CO3	DMF	9
3	CuBr (10)	L-Proline (20)	K2CO3	DMF	20
4	Cu(OAc)2·H2O (10)	L-Proline (20)	K2CO3	DMF	13
5	CuOTf (10)	L-Proline (20)	K2CO3	DMF	31
6	CuSO4 (10)	L-Proline (20)	K2CO3	DMF	26
7	CuI (20)	L-Proline (40)	K2CO3	DMF	55
8	CuI (30)	L-Proline (60)	K2CO3	DMF	50
9	CuI (20)	L-Proline (40)	K3PO4	DMF	38
10	CuI (20)	L-Proline (40)	^tBuOK	DMF	30
11	CuI (20)	L-Proline (40)	CsCO3	DMF	10
12	CuI (20)	L-Proline (40)	Na2CO3	DMF	8
13	CuI (20)	L-Proline (40)	NaOMe	DMF	11
14	CuI (20)	L-Proline (40)	Et3N	DMF	—^c
15	CuI (20)	L-Proline (40)	DBU	DMF	6
16	CuI (20)	L-Proline (40)	K2CO3	DMSO	62
17	CuI (20)	L-Proline (40)	K2CO3	NMP	28
18	CuI (20)	L-Proline (40)	K2CO3	DMA	37
19	CuI (20)	L-Proline (40)	K2CO3	Dioxane	10
20	CuI (20)	L-Proline (40)	K2CO3	Toluene	—^d
21	CuI (20)	L-Proline (40)	K2CO3	PEG-400	—
22	CuI (20)	Glycine (40)	K2CO3	DMSO	38
23	CuI (20)	DMEDA (40)	K2CO3	DMSO	42
24	CuI (20)	1,10-Phen^e (40)	K2CO3	DMSO	12
25	CuI (20)	8-HQ^f (40)	K2CO3	DMSO	9
26	—	L-Proline (40)	K2CO3	DMSO	—^c
27	CuI (20)	—	K2CO3	DMSO	20

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With the optimized reaction condition in hand (Table 1, entry 16), we explored the substrate generality for this tandem reaction by employing the substituted 2-bromobenzaldehydes and active methylene nitriles (Table 2). Reactions of substituted 2-bromobenzaldehydes 1a–c with different active methylene nitriles 2a–e gave corresponding 2-aminoquinolines in moderate to good yields (4aa–ae). The method tolerated different functional groups such as cyano, methoxy, ester, and amide. Structures of all the compounds were confirmed by IR, NMR (¹H & ¹³C) and HRMS data (ESI‡).

Table 2 Synthesis of 2-aminoquinolines

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Notably, when benzoylacetonitrile (X = ArCO, 3) was used as an active methylene nitrile, instead of expected 2-aminoquinoline, 2-phenylquinoline-3-carbonitrile (5aa) was obtained in 59% yield. Formation of 5aa prompted us to evaluate the regioselectivity of this reaction for benzoylacetonitriles. As can be seen from Table 2, benzoylacetonitriles containing methyl, methoxy, dioxole and chloro substituent reacted efficiently with 2-bromobenzaldehydes to give corresponding quinoline-3-carbonitriles (5aa–ah) in moderate to good yields. Similarly, 2-bromobenzaldehydes bearing methoxy and chloro groups were treated with different substituted benzoylacetonitriles to give corresponding 2-arylquinoline-3-carbonitriles in moderate to good yields (5ba–ch).

Control experiments were performed to evaluate the possible reaction pathway for the tandem sequences to produce 4aa and 5aa (Scheme 2). Initially, 2-bromobenzaldehyde (1a) was reacted with ethyl cyanoacetate using K₂CO₃ in DMSO at room temperature for 30 min, only Knoevenagel adduct 6 was obtained in 78% yield (Scheme 2A). When adduct 6, NaN₃, CuI, L-proline and K₂CO₃ were heated at 150 °C for 2 h, only the desired product 4aa was isolated in 70% yield (Scheme 2B). Exclusive formation of 4aa can be due to the relative reactivity of cyano group over ester in 6. Reaction of 1a with NaN₃, CuI, L-proline and K₂CO₃ at 120 °C gave 2-aminobenzaldehyde (8) in 64% yield (Scheme 2C). However, treatment of 1a with ethyl cyanoacetate in the presence of NaN₃, CuI, L-proline and K₂CO₃ at room temperature exclusively resulted in adduct 6. When the same reaction mixture was heated at 100 °C, ethyl 3-(2-aminophenyl)-2-cyanoacrylate (9) was obtained in 50% yield along with the desired product 4aa in 8% yield (Scheme 2D). Further, when 9 was heated at 150 °C in the presence of K₂CO₃ in DMSO, 4aa was obtained in 33% yield after 5 h, and 9 was recovered in 46% yield (Scheme 2E). From these control experiments, we concluded that ethyl 3-(2-bromophenyl)-2-cyanoacrylate (6) and ethyl 3-(2-aminophenyl)-2-cyanoacrylate (9) are key intermediates for the formation of 2-aminoquinoline. Similarly, reaction of 1a with 3a in absence of copper catalyst gave 2-benzoyl-3-(2-bromophenyl)acrylonitrile (10) which on reaction with NaN₃, CuI, L-proline and K₂CO₃ at 150 °C after 2 h resulted in exclusive formation of 5aa (Scheme 2F and G). This may be attributed to the relative electrophilicity of carbonyl group over nitrile group. Structure of 10 was confirmed NMR, mass and single X-ray analysis (CCDC 1433055, Fig. 2).

Scheme 2 Control experiments.

Fig. 2 ORTEP diagram (with 35% ellipsoid probability) for 10 (CCDC 1433055).

On the basis of control experiments and literature reports,^22a,24 a possible mechanism for the copper-catalyzed tandem reaction has been described (Scheme 3). Initially, the reaction of 2-brombenzaldehye and ethyl cyanoacetate generated Knoevenagel adduct 6. Reductive amination of 6 using sodium azide in the presence of copper catalyst produced 2-(2-aminobenzylidene)malononitrile (9). This is in accordance with earlier reports wherein sodium azide has been used as ammonia surrogate to prepare primary amines and nitrogen containing heterocycles in a copper catalyzed reductive amination of aryl halides.^14f,22c,22d Subsequently, intramolecular cyclization of 9 led to the formation of ethyl 2-aminoquinoline-3-carboxylate (4) via nucleophilic attack of amine onto nitrile followed by tautomerization. In case of benzoylacetonitrile, intermediate 10 formed after Knoevenagel condensation underwent reductive amination followed by intramolecular condensation to afford 2-arylquinoline-3-carbonitrile (5).

Scheme 3 A plausible mechanism for the synthesis of 4 and 5.

Next, the synthetic worth of the developed methodology was demonstrated by one-pot synthesis of pyrimido[4,5-b]quinolin-4(3H)-one derivatives (12a–c). In all the cases, reactions underwent smooth conversion to afford the corresponding pyrimido[4,5-b]quinolin-4(3H)-ones 12a–c in moderate to good (43–54%) yields (Scheme 4).

Scheme 4 Synthesis of pyrimido[4,5-b]quinolin-4(3H)-one.

Conclusions

In conclusion, we have successfully developed an efficient and straightforward copper-catalyzed regioselective synthesis of 2-aminoquinolines and 2-arylquinoline-3-carbonitriles from readily available 2-bromobenzaldehydes, active methylene nitriles and sodium azide. The developed three-component, one-pot tandem protocol displays broad substrate scope, good functional group tolerance and gives quinolines in moderate to good yields. The developed methodology can further be utilized for one-pot synthesis of pyrimido[4,5-b]quinolin-4(3H)-ones.

Experimental section

Melting points were determined in open capillary tubes on an automated melting point apparatus and are uncorrected. Reactions were monitored by using thin layer chromatography (TLC) on 0.2 mm silica gel F₂₅₄ plates. The chemical structures of final products were determined by their NMR spectra (¹H and ¹³C NMR). Chemical shifts are reported in parts per million (ppm) using deuterated solvent peak or tetramethylsilane as an internal standard. The HRMS data were recorded on a mass spectrometer with electrospray ionization and TOF mass analyzer. Some of benzoyl acetonitriles and 2-cyano acetamides were synthesized according to published procedure.²⁵ All other chemicals were obtained from the commercial suppliers and used without further purification.

Representative procedure for synthesis of 2-aminoquinolines (4)

A mixture of 2-bromobenzaldehyde (100 mg, 0.54 mmol), ethyl cyanoacetate (73 mg. 0.65 mmol), sodium azide (52 mg, 0.81 mmol), CuI (20 mol%), L-proline (40 mol%) and K₂CO₃ (186 mg, 2.5 equiv.) in DMSO (2 mL) was mixed under air atmosphere at room temperature and then heated to 150 °C for 3 h. After cooling to ambient temperature, the reaction mass was quenched with ice-cold aqueous solution of NH₄Cl (30 mL), filtered through a bed of celite and the plug washed with ethyl acetate (20 mL). The resulting filtrate was extracted with ethyl acetate (2 × 20 mL) and the combined organic layers dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Desired product 4aa (72 mg, 62%) was isolated by column chromatography on silica gel (100–200 mesh) using ethyl acetate/hexane (30%, v/v) as eluant.

Ethyl 2-aminoquinoline-3-carboxylate (4aa). Yellow solid; 72 mg (62%); mp 134–136 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.77 (s, 1H), 7.86 (dd, J = 8.1, 1.3 Hz, 1H), 7.63 (ddd, J = 8.4, 6.8, 1.5 Hz, 1H), 7.49 (d, J = 8.2 Hz, 1H), 7.26 (bs, 2H), 7.25–7.21 (m, 1H), 4.36 (q, J = 7.1 Hz, 2H), 1.37 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 166.5, 156.7, 150.0, 142.8, 133.0, 129.9, 125.1, 122.7, 122.0, 110.5, 61.6, 14.6; IR (KBr): 3418, 1697, 1628, 1288, 1080 cm⁻¹; HRMS for C₁₂H₁₃N₂O₂ [M + H⁺] calcd 217.0972, found 217.0976.

Ethyl 2-amino-7-methoxyquinoline-3-carboxylate (4ba). Yellow solid; 87 mg (66%); mp 138–140 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.65 (s, 1H), 7.74 (d, J = 9.5 Hz, 1H), 7.23 (bs, 2H), 6.86 (d, J = 6.2 Hz, 2H), 4.33 (q, J = 7.0 Hz, 2H), 3.86 (s, 3H), 1.35 (t, J = 7.0 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 166.8, 163.5, 157.4, 152.5, 142.1, 131.2, 117.1, 115.1, 107.1, 104.5, 61.3, 55.8, 14.6; IR (KBr): 3433, 1697, 1620, 1257, 1080 cm⁻¹; HRMS for C₁₃H₁₅N₂O₃ [M + H⁺] calcd 247.1077, found 247.1087.

Ethyl 2-amino-6,7-dimethoxyquinoline-3-carboxylate (4ca). Brown solid; 79 mg (53%); mp 190–193 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.60 (s, 1H), 7.28 (s, 1H), 6.99 (bs, 2H), 6.89 (s, 1H), 4.33 (q, J = 7.1 Hz, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 1.35 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 166.9, 156.3, 155.3, 148.0, 146.9, 140.4, 116.7, 107.8, 106.8, 105.0, 61.2, 56.1, 56.0, 14.6; IR (KBr): 3410, 1697, 1628, 1227, 1080 cm⁻¹; HRMS for C₁₄H₁₇N₂O₄ [M + H⁺] calcd 277.1183, found 277.1189.

2-Aminoquinoline-3-carboxamide (4ab). Light orange solid; 53 mg (52%); mp 195–196 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.48 (s, 1H), 8.24 (bs, 1H), 7.68 (d, J = 8.0 Hz, 1H), 7.61 (bs, 1H), 7.57 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.29–7.17 (m, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 170.4, 157.1, 149.2, 138.6, 131.6, 129.1, 125.3, 122.3, 122.2, 114.6; IR (KBr): 3410, 3194, 1636, 1389, 1227 cm⁻¹; HRMS for C₁₀H₁₀N₃O [M + H⁺] calcd 188.0818, found 188.0824.

2-Amino-7-methoxyquinoline-3-carboxamide (4bb). Orange solid; 64 mg (55%); mp 221–224 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.42 (s, 1H), 8.14 (bs, 1H), 7.56 (d, J = 8.6 Hz, 1H), 7.50 (bs, 1H), 7.27 (bs, 2H), 6.91–6.81 (m, 2H), 3.85 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 170.2, 162.4, 157.6, 151.3, 138.3, 130.3, 117.0, 114.4, 111.6, 104.7, 55.7; IR (KBr): 3378, 3209, 1620, 1381, 1227 cm⁻¹; HRMS for C₁₁H₁₂N₃O₂ [M + H⁺] calcd 218.0924, found 218.0930.

2-Amino-6,7-dimethoxyquinoline-3-carboxamide (4cb). Yellow solid; 73 mg (55%); mp 232–234 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.33 (s, 1H), 8.07 (bs, 1H), 7.43 (bs, 1H), 7.02 (s, 1H), 6.98 (bs, 2H), 6.89 (s, 1H), 3.87 (s, 3H), 3.82 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 170.4, 156.3, 154.1, 146.6, 146.3, 137.0, 116.4, 111.5, 107.2, 105.3, 56.0; IR (KBr): 3380, 3210, 1623, 1381, 1225 cm⁻¹; HRMS for C₁₂H₁₄N₃O₃ [M + H⁺] calcd 248.1030, found 248.1037.

(2-Aminoquinolin-3-yl)(pyrrolidin-1-yl)methanone (4ac). Brown oil; 52 mg (40%); ¹H NMR (400 MHz, DMSO-d₆) δ 8.07 (s, 1H), 7.71 (d, J = 7.7 Hz, 1H), 7.57–7.46 (m, 2H), 7.20 (t, J = 7.2 Hz, 1H), 6.49 (s, 2H), 3.52 (t, J = 6.7 Hz, 2H), 3.38 (t, J = 6.3 Hz, 2H), 1.92–1.80 (m, 4H); ¹³C NMR (100 MHz, DMSO-d₆) δ 166.6, 155.1, 148.1, 136.2, 130.7, 128.6, 125.4, 122.3, 120.1, 48.7, 46.2, 26.2, 24.4; IR (KBr): 3410, 1651, 1457, 1380 cm⁻¹; HRMS for C₁₄H₁₆N₃O [M + H⁺] calcd 242.1288, found 242.1292.

(2-Aminoquinolin-3-yl)(morpholino)methanone (4ad). Yellow semisolid; 49 mg (35%); ¹H NMR (400 MHz, DMSO-d₆) δ 7.94 (s, 1H), 7.72 (d, J = 7.4 Hz, 1H), 7.57–7.49 (m, 2H), 7.22 (t, J = 7.9 Hz, 1H), 6.38 (bs, 2H), 3.62 (bs, 2H), 3.26 (bs, 2H), 1.60 (bs, 4H); ¹³C NMR (100 MHz, CDCl₃) δ 167.8, 155.0, 147.6, 136.0, 130.9, 127.9, 125.8, 123.2, 122.6, 118.0, 65.9, 24.5; IR (KBr): 3410, 1653, 1458, 1381 cm⁻¹; HRMS for C₁₀H₈N₃ [M + H⁺] calcd 258.1237, found 258.1243.

2-Aminoquinoline-3-carbonitrile (4ae). Yellow semisolid; 28 mg (31%); ¹H NMR (400 MHz, DMSO-d₆) δ 8.69 (s, 1H), 7.75 (dd, J = 8.1, 1.2 Hz, 1H), 7.66 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.51 (d, J = 8.6 Hz, 1H), 7.28 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 6.98 (bs, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ 156.2, 149.6, 145.8, 133.3, 129.0, 125.9, 123.2, 121.4, 117.0, 95.0; IR (KBr): 3444, 2253, 1659, 1480, 1373 cm⁻¹; HRMS for C₁₀H₈N₃ [M + H⁺] calcd 170.0713, found 170.0719.

Representative procedure for synthesis of 2-arylquinoline-3-carbonitriles (5)

A mixture of 2-bromobenzaldehyde (100 mg, 0.54 mmol), benzoylacetonitriles (94 mg, 0.65 mmol), sodium azide (52 mg, 0.81 mmol), CuI (20 mol%), L-proline (40 mol%) and K₂CO₃ (186 mg, 2.5 equiv.) in DMSO (2 mL) was mixed under air atmosphere at room temperature and then heated to 150 °C for 3 h. After cooling to ambient temperature, the reaction mass was quenched with ice-cold aqueous solution of NH₄Cl (30 mL), filtered through a bed of celite and the plug washed with ethyl acetate (20 mL). The resulting filtrate was extracted with ethyl acetate (2 × 20 mL) and the combined organic layers dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Desired product 5aa (73 mg, 59%) was isolated by column chromatography on silica gel (100–200 mesh) using ethyl acetate/hexane (10%, v/v) as eluant.

2-Phenylquinoline-3-carbonitrile (5aa). Off white solid; 73 mg (59%); mp 193–195 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.70 (s, 1H), 8.23 (d, J = 8.4 Hz, 1H), 8.02 (dd, J = 7.8, 1.7 Hz, 2H), 7.97–7.89 (m, 2H), 7.75–7.66 (m, 1H), 7.64–7.52 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.1, 148.7, 144.3, 137.7, 133.1, 130.1, 129.9, 129.2, 128.8, 128.1, 127.8, 125.0, 117.9, 105.5; IR (KBr): 3055, 2222, 1620, 1450, 1373 cm⁻¹; HRMS for C₁₆H₁₁N₂ [M + H⁺] calcd 231.0917, found 231.0920.

2-p-Tolylquinoline-3-carbonitrile (5ab). Pale yellow solid; 54 mg (41%); mp 174–177 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.21 (d, J = 9.1 Hz, 1H), 8.01–7.84 (m, 4H), 7.67 (td, J = 7.4, 1.0 Hz, 1H), 7.40 (d, J = 7.9 Hz, 2H), 2.48 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.0, 148.7, 144.2, 140.6, 134.9, 132.9, 129.9, 129.5, 129.1, 127.9, 127.7, 124.9, 118.1, 105.5, 21.4; IR (KBr): 2916, 2222, 1612, 1481, 1188 cm⁻¹; HRMS for C₁₇H₁₃N₂ [M + H⁺] calcd 245.1073, found 245.1070.

2-(4-Methoxyphenyl)quinoline-3-carbonitrile (5ac). Off white solid; 63 mg (45%); mp 174–177 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.65 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.07–7.99 (m, 2H), 7.95–7.87 (m, 2H), 7.69–7.61 (m, 1H), 7.14–7.06 (m, 2H), 3.92 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 161.5, 157.5, 148.7, 144.3, 132.9, 130.7, 130.2, 129.8, 127.8, 127.7, 124.8, 118.3, 114.2, 105.3, 55.5; IR (KBr): 2914, 2221, 1612, 1481, 1173 cm⁻¹; HRMS for C₁₇H₁₃N₂O [M + H⁺] calcd 261.1022, found 261.1028.

2-(3,4-Dimethoxyphenyl)quinoline-3-carbonitrile (5ad). Off white solid; 78 mg (50%); mp 174–177 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.67 (s, 1H), 8.21 (d, J = 9.0 Hz, 1H), 7.92 (s, 1H), 7.89 (dd, J = 7.5, 1.2 Hz, 1H), 7.67 (ddd, J = 9.2, 8.2, 1.6 Hz, 2H), 7.62 (d, J = 2.1 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 4.04 (s, 3H), 4.00 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 157.4, 150.8, 149.1, 148.7, 144.4, 133.0, 130.2, 129.8, 127.8, 127.7, 124.8, 122.4, 118.3, 112.1, 111.0, 105.3, 56.1, 56.0; IR (KBr): 2916, 2222, 1615, 1483, 1180 cm⁻¹; HRMS for C₁₈H₁₅N₂O₂ [M + H⁺] calcd 291.1128, found 291.1124.

2-o-Tolylquinoline-3-carbonitrile (5ae). Yellow solid; 42 mg (32%); mp 163–164 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.56 (s, 1H), 8.11 (d, J = 8.5 Hz, 1H), 7.84 (d, J = 7.5 Hz, 1H), 7.82–7.78 (m, 1H), 7.60 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 7.33 (ddd, J = 9.6, 6.4, 2.7 Hz, 2H), 7.27 (d, J = 7.0 Hz, 2H), 2.22 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.9, 148.3, 142.5, 137.6, 136.1, 132.9, 130.8, 129.8, 129.6, 129.2, 128.2, 127.9, 126.0, 125.1, 117.1, 107.5, 19.7; IR (KBr): 3015, 2222, 1616, 1473, 1170 cm⁻¹; HRMS for C₁₇H₁₃N₂ [M + H⁺] calcd 245.1073, found 245.1076.

2-(2-Methoxyphenyl)quinoline-3-carbonitrile (5af). Pale yellow solid; 63 mg (45%); mp 150–153 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.61 (s, 1H), 8.23 (d, J = 9.3 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.89 (ddd, J = 8.5, 7.0, 1.5 Hz, 1H), 7.69 (ddd, J = 8.1, 7.0, 1.1 Hz, 1H), 7.59–7.49 (m, 2H), 7.17 (td, J = 7.5, 0.9 Hz, 1H), 7.09 (d, J = 8.3 Hz, 1H), 3.91 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 157.3, 157.0, 148.7, 142.3, 132.5, 131.5, 131.0, 130.0, 128.0, 127.3, 125.1, 121.2, 117.7, 111.3, 108.8, 55.4; IR (KBr): 3015, 2222, 1616, 1473, 1170 cm⁻¹; HRMS for C₁₇H₁₃N₂O [M + H⁺] calcd 261.1022, found 261.1032.

2-(Benzo[d][1,3]dioxol-5-yl)quinoline-3-carbonitrile (5ag). Light brown solid; 62 mg (42%); mp 187–189 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.64 (s, 1H), 8.16 (d, J = 8.9 Hz, 1H), 7.88 (t, J = 7.4 Hz, 2H), 7.64 (t, J = 7.2 Hz, 1H), 7.55 (dd, J = 8.1, 1.7 Hz, 1H), 7.50 (d, J = 1.6 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.07 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 157.3, 149.4, 148.6, 148.2, 144.4, 133.0, 131.7, 129.8, 127.9, 127.7, 124.9, 123.9, 118.1, 109.5, 108.5, 105.3, 101.6; IR (KBr): 3015, 2222, 1616, 1473, 1170 cm⁻¹; HRMS for C₁₇H₁₁N₂O₂ [M + H⁺] calcd 275.0815, found 275.0820.

2-(4-Chlorophenyl)quinoline-3-carbonitrile (5ah). White solid; 93 mg (65%); mp 188–190 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.69 (s, 1H), 8.21 (d, J = 8.8 Hz, 1H), 7.99 (d, J = 8.5 Hz, 2H), 7.93 (t, J = 7.1 Hz, 2H), 7.70 (t, J = 7.5 Hz, 1H), 7.56 (d, J = 8.5 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 156.7, 148.6, 144.3, 136.5, 136.1, 133.2, 130.5, 129.9, 129.0, 128.3, 127.8, 125.1, 117.8, 105.3; IR (KBr): 2914, 2221, 1612, 1481, 1173 cm⁻¹; HRMS for C₁₆H₁₀ClN₂ [M + H⁺] calcd 265.0527, found 265.0524.

7-Methoxy-2-phenylquinoline-3-carbonitrile (5ba). Off white solid; 87 mg (62%); mp 164–166 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.56 (s, 1H), 7.99 (d, J = 6.2 Hz, 2H), 7.80 (d, J = 9.0 Hz, 1H), 7.60–7.51 (m, J = 5.8 Hz, 3H), 7.52 (d, J = 1.9 Hz, 1H), 7.31 (dd, J = 9.0, 2.3 Hz, 1H), 4.01 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 163.6, 158.8, 150.9, 143.3, 137.9, 130.0, 129.1, 128.9, 128.7, 121.7, 120.4, 118.4, 107.7, 102.9, 55.9; IR (KBr): 3015, 2214, 1620, 1443, 1142 cm⁻¹; HRMS for C₁₇H₁₃N₂O [M + H⁺] calcd 261.1022, found 261.1028.

6,7-Dimethoxy-2-phenylquinoline-3-carbonitrile (5ca). Pale yellow solid; 64 mg (41%); mp 196–199 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.45 (s, 1H), 7.97 (dd, J = 8.0, 1.4 Hz, 2H), 7.59–7.52 (m, 3H), 7.51 (s, 1H), 7.10 (s, 1H), 4.08 (s, 3H), 4.06 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 156.6, 155.3, 151.0, 146.5, 141.2, 138.0, 129.7, 129.0, 128.7, 121.0, 118.6, 108.3, 104.6, 103.2, 56.5, 56.3; IR (KBr): 2924, 2222, 1620, 1504, 1185 cm⁻¹; HRMS for C₁₈H₁₅N₂O₂ [M + H⁺] calcd 291.1128, found 291.1125.

6-Methoxy-2-phenylquinoline-3-carbonitrile (5da). Yellow solid; 84 mg (60%); mp 167–168 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.54 (s, 1H), 8.11 (d, J = 9.2 Hz, 1H), 8.00 (dd, J = 8.0, 1.5 Hz, 2H), 7.63–7.50 (m, 4H), 7.13 (d, J = 2.7 Hz, 1H), 3.99 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.9, 155.7, 145.0, 142.5, 137.8, 131.3, 129.8, 129.0, 128.7, 126.2, 126.1, 118.2, 105.7, 104.6, 55.8; IR (KBr): 2945, 2222, 1620, 1489, 1034 cm⁻¹; HRMS for C₁₇H₁₃N₂O [M + H⁺] calcd 261.1022, found 261.1025.

6-Chloro-2-phenylquinoline-3-carbonitrile (5ea). Pale yellow solid; 36 mg (25%); mp 190–193 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.61 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 8.04–8.00 (m, 2H), 7.92 (d, J = 2.3 Hz, 1H), 7.85 (dd, J = 9.0, 2.3 Hz, 1H), 7.62–7.57 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.2, 147.1, 143.2, 137.3, 134.1, 133.9, 131.5, 130.4, 129.1, 128.8, 126.3, 125.6, 117.6, 106.6; IR (KBr): 3053, 2222, 1597, 1489, 1026, 764 cm⁻¹; HRMS for C₁₆H₁₀ClN₂ [M + H⁺] calcd 265.0527, found 265.0524.

6,7-Dimethoxy-2-p-tolylquinoline-3-carbonitrile (5cb). Pale yellow solid; 49 mg (30%); mp 198–200 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.44 (s, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.51 (s, 1H), 7.37 (d, J = 7.9 Hz, 2H), 7.09 (s, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 2.46 (s, 4H); ¹³C NMR (100 MHz, CDCl₃) δ 156.6, 155.3, 150.9, 146.5, 141.3, 139.9, 135.1, 129.4, 128.9, 120.9, 118.7, 108.27, 104.6, 103.1, 56.5, 56.3, 21.4; IR (KBr): 2924, 2214, 1690, 1504, 1211 cm⁻¹; HRMS for C₁₉H₁₇N₂O₂ [M + H⁺] calcd 305.1285, found 305.1291.

6,7-Dimethoxy-2-(4-methoxyphenyl)quinoline-3-carbonitrile (5cc). Pale yellow solid; 60 mg (35%); mp 178–180 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.41 (s, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.48 (s, 1H), 7.08 (d, J = 5.0 Hz, 2H), 7.06 (s, 1H), 4.07 (s, 3H), 4.05 (s, 3H), 3.90 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 160.9, 156.1, 155.2, 150.8, 146.5, 141.3, 130.5, 130.4, 120.7, 118.83, 114.1, 108.2, 104.5, 102.9, 56.5, 56.3, 55.4; IR (KBr): 2925, 2213, 1612, 1494, 1173 cm⁻¹; HRMS for C₁₉H₁₇N₂O₃ [M + H⁺] calcd 321.1234, found 321.1238.

2-(4-Chlorophenyl)-6,7-dimethoxyquinoline-3-carbonitrile (5ch). White solid; 75 mg (43%); mp 234–235 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.45 (s, 1H), 7.98–7.90 (m, 2H), 7.57–7.51 (m, 2H), 7.49 (s, 1H), 7.11 (s, 1H), 4.09 (s, 3H), 4.08 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 155.5, 155.2, 151.2, 146.5, 141.3, 136.4, 136.1, 130.3, 128.9, 121.2, 118.4, 108.2, 104.5, 102.9, 56.54, 56.3; IR (KBr): 2947, 2222, 1697, 1504, 1165 cm⁻¹; HRMS for C₁₈H₁₄ClN₂O₂ [M + H⁺] calcd 325.0738, found 325.0734.

Ethyl 3-(2-bromophenyl)-2-cyanoacrylate (6)

Colorless oil, 78%; ¹H NMR (400 MHz, CDCl₃) δ 8.63 (s, 1H), 8.17 (dd, J = 7.8, 1.6 Hz, 1H), 7.71 (dd, J = 8.0, 1.2 Hz, 1H), 7.46 (td, J = 7.4, 0.8 Hz, 1H), 7.38 (td, J = 7.7, 1.7 Hz, 1H), 4.41 (q, J = 7.1 Hz, 1H), 1.41 (t, J = 7.1 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 161.8, 153.9, 133.7, 133.6, 131.7, 130.1, 128.1, 126.6, 114.7, 106.4, 63.0, 14.2; HRMS for C₁₂H₁₁BrNO₂ [M + H⁺] calcd 279.9968, found 279.9973 and 281.9954 [M + 2 + H⁺].

2-Aminobenzaldehyde (8)

Pale yellow liquid; 42 mg (64%); ¹H NMR (400 MHz, DMSO-d₆) δ 9.81 (d, J = 0.4 Hz, 1H), 7.53 (dd, J = 7.8, 1.6 Hz, 1H), 7.30 (ddd, J = 8.5, 7.0, 1.7 Hz, 1H), 7.12 (bs, 2H), 6.76 (d, J = 8.4 Hz, 1H), 6.64 (ddd, J = 7.9, 7.0, 1.0 Hz, 1H); ¹³C NMR (100 MHz, DMSO-d₆) δ 194.5, 151.2, 136.0, 135.5, 118.2, 116.3, 115.4; HRMS for C₇H₈NO [M + H⁺] calcd 122.0600, found 121.0581.

Ethyl 3-(2-aminophenyl)-2-cyanoacrylate (9)

Brown solid; 58 mg (50%); mp 123–125 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 8.55 (s, 1H), 8.32 (d, J = 8.6 Hz, 1H), 8.09 (d, J = 7.9 Hz, 1H), 7.84 (d, J = 8.2 Hz, 3H), 7.47 (t, J = 7.4 Hz, 1H), 4.42 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 165.50, 147.65, 141.08, 133.74, 130.93, 130.68, 125.00, 120.86, 117.26, 110.72, 62.23, 14.54; ¹H NMR (400 MHz, DMSO-d₆, D₂O exchange) δ 8.58 (s, 1H), 8.26 (d, J = 8.5 Hz, 1H), 8.04 (d, J = 7.7 Hz, 1H), 7.85 (t, J = 7.6 Hz, 1H), 7.47 (t, J = 7.3 Hz, 1H), 4.39 (q, J = 6.9 Hz, 2H), 1.37 (t, J = 7.0 Hz, 3H); HRMS for C₁₂H₁₃N₂O₂ [M + H⁺] calcd 217.0972, found 217.0975.

2-Benzoyl-3-(2-bromophenyl)acrylonitrile (10)

Crystalline off white solid; 234 mg (70%); mp 126–128 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.37 (s, 1H), 8.25 (d, J = 7.1 Hz, 1H), 7.94 (d, J = 7.3 Hz, 2H), 7.73 (d, J = 7.8 Hz, 1H), 7.68 (t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.6 Hz, 2H), 7.51 (t, J = 7.6 Hz, 1H), 7.42 (t, J = 7.7 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 188.8, 154.1, 135.3, 133.8, 133.7, 133.6, 132.1, 130.10, 129.6, 128.8, 128.2, 126.5, 115.7, 113.6; HRMS for C₁₆H₁₁BrNO [M + H⁺] calcd 312.0019, found 312.0015.

Ethyl 3-(2-azidophenyl)-2-cyanoacrylate (11)

¹H NMR (400 MHz, CDCl₃) δ 8.79 (s, 1H), 8.78 (d, J = 9.0 Hz, 1H), 8.14 (dd, J = 8.1, 1.1 Hz, 1H), 8.04 (td, J = 8.4, 7.9, 1.3 Hz, 1H), 7.85–7.80 (m, 1H), 4.64 (q, J = 7.1 Hz, 2H), 1.55 (t, J = 7.1 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 162.6, 145.7, 138.1, 133.6, 132.0, 130.5, 128.6, 122.7, 117.2, 117.1, 62.7, 14.4. MS (ESI) m/z calcd for C₁₂H₁₁N₄O₂ [M + H⁺] 243.09, found 243.15.

Representative procedure for synthesis of pyrimido[4,5-b]quinolin-4(3H)-ones (12)

A mixture of 2-bromobenzaldehyde (100 mg, 0.54 mmol), 2-cyanoacetamide (54 mg, 0.65 mmol), sodium azide (52 mg, 0.81 mmol), CuI (20 mol%), L-proline (40 mol%) and K₂CO₃ (186 mg, 2.5 equiv.) in DMSO (2 mL) was mixed under air atmosphere at room temperature and then heated to 150 °C for 3 h. After cooling to ambient temperature, benzaldehyde (69 mg, 0.65 mmol) was added and reaction mixture was then again heated to 150 °C for 2 h. After cooling to ambient temperature, the reaction mass was quenched with ice-cold aqueous solution of NH₄Cl (30 mL), filtered through a bed of celite and the plug washed with ethyl acetate (20 mL). The resulting filtrate was extracted with ethyl acetate (2 × 20 mL) and the combined organic layers dried over anhydrous Na₂SO₄ and concentrated under reduced pressure. Desired product 12a (77 mg, 52%) was isolated by column chromatography on silica gel (100–200 mesh) using ethyl acetate/hexane (30%, v/v) as eluent.

2-Phenylpyrimido[4,5-b]quinolin-4(3H)-one (12a). Yellow solid; 77 mg (52%); mp 356–357 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 12.71 (s, 1H), 9.32 (s, 1H), 8.30–8.27 (m, 3H), 8.10 (d, J = 8.6 Hz, 1H), 7.96 (t, J = 7.6 Hz, 1H), 7.72–7.57 (m, 4H); ¹³C NMR (100 MHz, DMSO-d₆) δ 163.7, 156.8, 156.3, 151.6, 138.6, 133.3, 133.1, 132.6, 130.0, 129.2, 128.9, 128.6, 126.9, 126.7, 116.1; HRMS for C₁₇H₁₂N₃O [M + H]⁺ calcd 274.0975, found 274.0978.

2-(p-Tolyl)pyrimido[4,5-b]quinolin-4(3H)-one (12b). Orange solid; 84 mg (54%); mp 304–306 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 12.62 (s, 1H), 9.29 (s, 1H), 8.26 (d, J = 8.1 Hz, 1H), 8.20 (d, J = 8.0 Hz, 2H), 8.08 (d, J = 8.6 Hz, 1H), 7.94 (t, J = 8.5 Hz, 1H), 7.66 (t, J = 7.3 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 163.7, 156.9, 156.1, 151.6, 142.8, 138.6, 133.3, 130.2, 130.0, 129.8, 128.9, 128.6, 126.8, 126.6, 116.0, 21.5; HRMS for C₁₈H₁₄N₃O [M + H]⁺ calcd 288.1131, found 288.1127.

2-(4-Chlorophenyl)pyrimido[4,5-b]quinolin-4(3H)-one (12c). Yellow solid; 72 mg (43%); mp 376–378 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 12.80 (s, 1H), 9.32 (s, 1H), 8.32–8.28 (m, 3H), 8.10 (d, J = 8.6 Hz, 1H), 7.96 (t, J = 7.4 Hz, 1H), 7.70–7.67 (m, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 156.6, 151.5, 138.7, 137.5, 133.4, 132.0, 130.5, 130.1, 130.0, 129.3, 129.0, 128.9, 127.0, 126.7, 116.1; HRMS for C₁₇H₁₁ClN₃O [M + H]⁺ calcd 308.0585, found 308.0582.

Acknowledgements

We sincerely acknowledge financial support from Ranbaxy Laboratories Pvt. Ltd. (India) to carry out this work. HKS is grateful to CSIR, New Delhi, India for senior research fellowship. Authors thank Prof. Alaknanda Hajra for his help in recording and analyzing single-crystal X-ray diffraction data for intermediate 10 and Miss Pinku Kaswan for her kind suggestions and discussion.

Notes and references

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Footnotes

† Presented in International Conference on “Nascent Development in Chemical Sciences: Opportunities for Academia-Industry Collaboration” at BITS Pilani during October 16–18, 2015 and selected for best poster award sponsored by RSC.

‡ Electronic supplementary information (ESI) available: Copies of ¹H NMR, ¹³C NMR spectra for all the synthesized compounds and tables for single X-ray data of 10. CCDC 1433055. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ra03798d

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