Multicomponent cascade reaction: dual role of copper in the synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline and their photophysical studies

Abstract

One-pot synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines through a multi-component reaction is demonstrated. The domino/cascade reaction proceeds via click reaction, in which 1,2,3-triazole motif augment methylene group reactivity/N–C bond formation/Knoevenagel condensation in sequence. Overall one C–C bond and three C–N bonds are formed in a single step. In addition, photophysical properties of these new compounds were studied and compound 5u emerged as good fluorogenic substrate with quantum yield ∼0.21.

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Introduction

Multi-component reactions (MCRs) turned out to be a potentially more efficient synthetic strategy, which attributes renaissance in organic synthesis to afford sustainable and diversity-oriented functionalized molecules.¹ In particular, metal catalysed MCRs are recently the choice of interest² owing to instinctive drawbacks involved in a multistep synthesis.

In this context, we focused our attention on MCR catalysed by inexpensive and abundant copper salts to perform more than one distinct catalytic process in one pot. Various research groups have revealed dual catalytic behaviour of copper³ viz., Swamy et al. executed [3 + 2] cycloaddition between azide and alkyne to afford 1,2,3-triazole followed by intramolecular C₅–H arylation and O–C bond formation with haloarenes in sequence.^3e,4 Sun et al. synthesized benzo[f]indole-4,9-diones in which copper was a Lewis acid and oxidative catalyst.⁵ Pawar et al. illustrated the role of copper both in the generation of cyanide units from N,N-dimethylformamide–ammonia and in the cyanation of aryl halides.⁶ Hence, we combined MCR and the dual role of copper catalyst to synthesize versatile molecules.

To implement the above strategy, we decided to synthesize 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline as these two heterocyclic moieties are widely applicable in biological systems, material chemistry, and especially as fluorescent sensors, dye-sensitized solar cells, etc.^7–9 Some of the prominent 1,2,3-triazole tethered molecules with pharmaceutical and fluorescence applications are depicted in Fig. 1.^7,8 Hranjec et al. explored the expediency of benzimidazo[1,2-a]quinoline analogues in various domains.⁹ Copious synthetic strategies are available to accomplish this aza-fused heterocycle.^10,11 In many instances the bottleneck to facilitate the key step (Knoevenagel condensation) is pre-functionalization of the methylene bridge with an electron withdrawing group (–CN, –CO₂R, –COR, –SO₂R) which restricts synthetic modification of molecules. As a result, MCR emphasizing the dual role of copper to synthesize 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines and exploration of their photophysical properties in the current study was undertaken.

Fig. 1 1,2,3-Triazole tethered molecules of pharmaceutical and fluorescence application.^7,8

We herein demonstrated the synthesis of such molecules starting from a non-activated readily prepared precursor like 1,2,3-triazole, which was formed in situ, and studied its influence in activating a methylene link to undergo Knoevenagel condensation. Hitherto, only a couple of published examples existed based on a click and activate approach to synthesize 1,2,3-triazole tethered 2-quinolinone and iminochromene.¹² Furthermore, advancement of this unique arena is not explored much, so this ingenuity opens the window for chemists to develop 1,2,3-triazole anchored fused heterocycles. Thus, in one synthetic operation we envisioned a three component domino process via click reaction/N–C bond formation/Knoevenagel condensation (Fig. 2).

Fig. 2 Design strategy of 1,2,3-triazole appended benzimidazo[1,2-a]quinoline.

Results and discussion

At the outset, we began to assemble 1,2,3-triazole tethered benzimidazo[1,2-a]quinolines in a two-step process as depicted in Scheme 1. The reactants 2-(azidomethyl)-1H-benzo[d]imidazole (1a) and phenylacetylene (3a) were subjected to [3 + 2] cycloaddition in the presence of CuSO₄·5H₂O, sodium ascorbate in t-BuOH : H₂O (1 : 1) at room temperature for 30 min. After completion of the reaction, it was diluted with water and the resultant solid was filtered to yield 2-((4-phenyl-1H-1,2,3-triazol-1-yl)methyl)-1H-benzo[d]imidazole (4a) in 94% yield. The structure of product 4a was confirmed from its analytical data. In the ¹H NMR spectrum, methylene (–CH₂–) bridged protons resonated at δ 5.89 ppm and a singlet at 8.05 ppm resonated due to the C₅–H of 1,2,3-triazole. Later, we treated 4a with 2-bromobenzaldehyde (2a) in the presence of CuI (0.1 mmol)/TMEDA (0.2 mmol)/Cs₂CO₃ (3 mmol) in DMSO at 100 °C for 18 h under N₂ atmosphere. To our delight, we isolated the desired product 5a in 44% yield. The structure of 5a was characterised by spectral data. In the ¹H NMR spectrum, disappearance of a singlet at δ 5.89 ppm due to methylene (–CH₂–) bridged protons and a broad peak at δ 12.2 ppm due to benzimidazole N–H were noticed. Also a singlet appeared at δ 9.84 ppm for highly deshielded C₅–H along with other protons at their respective positions amply warranted the product formation. With this appealing and heartening result handy, we focussed on how to alleviate this sequential transformation.

Scheme 1 Synthesis of target molecule over two step procedure.

As a next step, we steered our attempts to carry out MCR by employing 2-(azidomethyl)-1H-benzo[d]imidazole (1a), 2-bromobenzaldehyde (2a) and phenylacetylene (3a) as condensation partners. These three components were mixed with CuI (0.1 mmol)/TMEDA (0.2 mmol)/Cs₂CO₃ (3 mmol) in DMSO and were heated at 100 °C for 18 h under N₂ atmosphere. After purification, we isolated the desired product in 36% yield and in this process overall four new bonds (1C–C and 3C–N) were formed in a single step (Scheme 2). With this encouraging result, we then focused our attention on optimizing the reaction conditions by screening various parameters such as catalysts, ligands, bases, solvents, and temperature to obtain a satisfactory yield for this MCR and the results are summarized in Table 1.

Scheme 2 Synthesis of target molecule in one-pot.

Table 1 Optimization of cascade reaction conditions^a

Entry	Catalyst	Ligand	Base	Solvent	T (°C)/time	Yield^b%
a Quantities used: 2-(azidomethyl)-1H-benzo[d]imidazole (1 mmol), 2-bromobenzaldehyde (1 mmol) and phenylacetylene (1 mmol), catalyst (0.1 mmol), ligand (0.2 mmol), base (3 mmol), solvent (2 mL).b Yields are for isolated products.c Complex reaction mixture.d No reaction, triazole 4a remained unconsumed (entry 14 – 81%; entry 19 – 79%).e CuI (0.05 mmol), ligand (0.1 mmol).f K2CO3 (2.5 mmol).
1	CuI	(L)-Proline	Cs2CO3	DMSO	100/8 h	43
2	CuI	1,10-Phenanthroline	Cs2CO3	DMSO	100/12 h	42
3	CuI	8-Hydroxyquinoline	Cs2CO3	DMSO	100/12 h	46
4	CuI	Picolinic acid	Cs2CO3	DMSO	100/8 h	52
5	CuI	Picolinic acid	KOt-Bu	DMSO	100/8 h	CR^c
6	CuI	Picolinic acid	DBU	DMSO	100/8 h	CR^c
7	CuI	Picolinic acid	K3PO4	DMSO	100/10 h	72
8	CuI	Picolinic acid	K2CO3	DMSO	100/8 h	89
9	CuBr	Picolinic acid	K2CO3	DMSO	100/8 h	79
10	CuCl	Picolinic acid	K2CO3	DMSO	100/8 h	47
11	Cu2O	Picolinic acid	K2CO3	DMSO	100/8 h	CR^c
12	CuI	Picolinic acid	K2CO3	DMF	100/8 h	45
13	CuI	Picolinic acid	K2CO3	DMA	100/8 h	52
14	CuI	Picolinic acid	K2CO3	ACN	80/24 h	NR^d
15	CuI	Picolinic acid	K2CO3	PEG-400	100/18 h	86
16^e	CuI	Picolinic acid	K2CO3	PEG-400	120/18 h	74
17^f	CuI	Picolinic acid	K2CO3	PEG-400	120/14 h	84
18	CuI	Picolinic acid	K2CO3	PEG-400	120/8 h	93
19	CuI	Picolinic acid	K2CO3	Water	100/24 h	NR^d

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An augment to the yield (43%) along with accelerating reaction time (8 h) was noticed when the utility of L-proline was tested (Table 1, entry 1). Among others, 1,10-phenanthroline and 8-hydroxyquinoline, even with longer reaction times, didn't significantly influence the yield (entries 2 and 3). Picolinic acid was found to be the ideal ligand because it promulgated the reaction to afford tandem product in 52% yield (entry 4). Later, effects of various bases were scrutinized (entries 5–8). KOt-Bu and DBU equally suppressed the reaction yielding a complex reaction mixture and K₃PO₄ required a longer reaction time (10 h) but with significant increase in the yield (entry 7, 72%). Gratifyingly, K₂CO₃ emerged to be the best possible base to afford the product in 89% yield (entry-8). Further, the effectiveness of various copper catalysts was examined (entries 9–11). CuBr and CuCl were found to give diminished yields, while Cu₂O was found to be detrimental and resulted in a complex reaction mass. Subsequently, the effect of altering polar protic and aprotic solvents was assessed (entries 12–19). Polar aprotic solvents in general did not fetch amenable yields, while acetonitrile and water afforded solely triazole 4a. Nevertheless, polyethylene glycol (PEG-400) at 100 °C for 18 h yielded 86% of product (entry 15). Decrease in the yield was observed when lower loadings of CuI (0.05 mmol), picolinic acid (0.1 mmol) (entry 16) and K₂CO₃ (2.5 mmol) (entry 17) were used. Taking advantage of PEG-400, which is a less toxic and environmentally benign solvent, we attempted the tandem reaction at 120 °C. Strikingly, that condition was revealed to be superior to all other solvent choices, affording the product in 93% yield (entry 18). Thus, the catalytic system employing CuI (0.1 mmol), picolinic acid (0.2 mmol) and K₂CO₃ (3 mmol) in PEG-400 at 120 °C for 8 h was revealed to be optimal in realizing this synthetic strategy.

With this fine-tuned MCR, further efforts were streamlined to expand the generality and scope of this methodology by varying different alkynes (Table 2). Hyperconjugated systems 4-ethynyltoluene and 4-tert-butylphenylacetylene reacted smoothly to afford the desired products in 88 and 72% yields, respectively (5b and 5c, Table 2). Electron-withdrawing phenylacetylenes bearing –Cl, –F and –CF₃ groups enhanced the yield of desired product 5e (75%), 5f (87%), and 5g (80%) when compared to electron-rich phenylacetylene 5d (–OMe, 72% yield). To make this protocol virtually more efficient, we were drawn towards dealing with low boiling aliphatic alkynes.

Table 2 Screening of diverse acetylenes for the MCR^a

a Quantities used: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol), K₂CO₃ (3 mmol), PEG-400 (2 mL).b Yields are for isolated products.

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Primarily, cyclopropylacetylene was subjected to MCR following our optimized condition but an unexpectedly lower yield of desired product (5h, 43%) was noticed. As the boiling point of the alkyne is low, heating at higher temperature might have resulted in lower yield. In order to circumvent the diminished yield, we slightly modified the procedure by mixing all the components of the reaction and stirred the resultant mixture at 50 °C for 1 h to predominantly favour the click reaction before elevating the operating temperature to 120 °C for 8 h. Encouragingly, the reaction proceeded with ease resulting in an improved yield of product (5h, 77%). This modified condition was conveniently employed to yield compound 5i in 71%. Subsequently, we used ethynyltrimethylsilane as an alkyne partner. As expected, product 5j was isolated in 88% yield after removal of the trimethylsilyl group due to the basic reaction medium along with higher temperature. Continuing with the aliphatic acetylenes, we decided to explore alkynes bearing an unprotected alcohol functional group; hence we carried the MCR with propargyl alcohol, 1a and 2a. To our surprise, the reaction was clean and the desired product 5k was obtained in 67% yield. Furthermore, to study the reactivity profile with alkyne, 2-ethynylpyridine was subjected to this MCR. As evident, the alkyne smoothly participated in this cascade reaction to afford the tandem product 5l in 76% yield.

We then proceeded to evaluate the scope of substituted 2-bromobenzaldehydes (Table 3). 2-Bromobenzaldehyde with one electron-rich group (–OMe) at C₅ position furnished a tandem product in good yield (5m, 64%), compared to 2-bromobenzaldehyde with two methoxy groups at C₄ and C₅ positions (5n, 52%). Also, 2-bromo-5-chlorobenzaldehyde furnished the tandem product 5o in good yield (67%). However, 2-bromobenzaldehyde with an electron-withdrawing group (–F) at C₅ position was found to favour the tandem reaction to provide 5p in 89% yield. As an extension, we tested our optimized condition on ortho-halo (hetero)aryl carboxaldehyde moieties to generate benzimidazo[1,2-a][1,8]naphthyridine derivatives. Such compounds have ample application in photophysical and biological properties such as a fluorescent chemodosimeter for detecting anionic species, OLEDs, and cannabinoid receptors.¹³ Typically, 2-bromo-3-pyridinecarboxaldehyde reacted smoothly to deliver desired product in 81% yield (5q). Conversely, when 2-chloro-8-methyl quinoline-3-carboxaldehyde was employed, decrease in the yield was noticed (5r, 60%). It is also worth mentioning that 5q and 5r took a shorter reaction time (6 h) primarily attributing to the reactivity of heteroaryl halides by a nucleophilic aromatic substitution (S_NAr) reaction via an addition-elimination mechanism.¹⁴

Table 3 Screening of diverse 2-bromo/chloro(hetero)aryl aldehyde for the MCR^a

a Quantities used: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol), K₂CO₃ (3 mmol), PEG-400 (2 mL).b Yields are for isolated products.

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Eventually, we turned our attention to explore the reactivity profile of substituted 2-(azidomethyl)-1H-benzo[d]imidazole. Substituents like –CH₃, –Cl and –F reacted smoothly to furnish the desired product in good yield (Table 4: 84%, 5s; 77%, 5t; 66%, 5u). This indicated that the electronic effect on a benzimidazole core doesn't impede the reactivity profile. By virtue of its reactivity, products were found to exist as mixtures of regioisomers in 1 : 1 ratio with substituents at C₉ and C₁₀ positions (position numbering on structures).

Table 4 Screening of diverse 2-(azidomethyl)-1H-benzo[d]imidazoles for the MCR^a

a Quantities used: 1 (1 mmol), 2 (1 mmol), 3 (1 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol), K₂CO₃ (3 mmol), PEG-400 (2 mL).b Yields are for isolated products.

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Furthermore, Verma et al. accounted for the utilization of benzotriazole based ligands with copper catalysis to synthesize various nitrogen heterocycles.¹⁵ Inspired by the remarkable ligand properties of the 1,2,3-triazole framework, we thus attempted the MCR employing a ligand-free condition (Scheme 3). Accordingly, 1a and 3a was coupled with 2-bromobenzaldehyde and 2-bromo-5-fluorobenzaldehyde. The former reaction took 20 h to provide 5a in 58% yield and the latter took 22 h to provide 5p in 53% yield. Nevertheless, a ligand-promoted reaction fetched the desired product in an appreciable yield (Table 2, 5a, 93% and Table 3, 5p, 89%) in comparison to a ligand-free reaction with a shorter reaction time of 8 h. Hence, we implemented picolinic acid as a ligand to accelerate the reaction for the synthesis of 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline analogues.

Scheme 3 MCR employing ligand-free condition.

To investigate the reaction sequence for formation of tandem products, we carried out two parallel reactions (Scheme 4). In first instance we performed N-arylation of 4a with bromobenzene and in the second instance we carried out Knoevenagel condensation of 4a with benzaldehyde employing the optimised reaction condition. Despite prolonged heating for 24 h, we did not notice N-arylated product in the former reaction and Knoevenagel condensed product in the latter reaction, intermediate 4a remained unconsumed. The failure of N-arylation could be attributed to steric effects rising from the methylene triazole and destabilizing the copper complex or the absence of a suitable coordinating group at ortho position of bromobenzene. In the latter case, the methylene group sandwiched between 1,2,3-triazole and benzimidazole heterocycles was not active enough to take part in a Knoevenagel condensation apparently due to a less acidic nature. Facts from the control experiment suggested that the bottleneck for this tandem process would be carbonyl group assisted N-arylation^14b,16 followed by Knoevenagel condensation.

Scheme 4 Control experiments.

The plausible mechanistic pathway for this MCR based on the outcome of control experiments and literature precedents is deduced (Scheme 5). Primarily, a click reaction between 1 and 3 resulted in the formation of compound 4 with augments in methylene group reactivity. On the other hand, an ortho-halo (hetero)aryl carbonyl compound forms a complex with the copper catalyst through oxidative addition to furnish intermediate I. Compound 4 upon deprotonation in the presence of base and metallation with the intermediate I would provide the intermediate II. Ultimately, reductive elimination of II furnishes the desired tandem product 5 through a domino process of N-arylation-Knoevenagel condensation to complete the catalytic cycle.

Scheme 5 Plausible mechanistic pathway for the formation of tandem product.

From the literature, a plethora of benzimidazo[1,2-a]quinoline core has been established as good fluorophore.^9c,9d Additionally, tailoring a 1,2,3-triazole moiety onto existing fluorophores has endowed remarkable photophysical properties.^8d,17 We therefore opted to examine the UV and fluorescence properties of a diversely oriented 1,2,3-triazole tethered benzimidazo[1,2-a]quinoline backbone and the spectral properties are summarised in Table 5 (for details see ESI S5 and S6†). The quantum yield was determined in CHCl₃ solution (within a maximum absorbance close to 0.1) and was calculated relative to the quantum yield of standard compound quinine sulphate in 0.1 M H₂SO₄ (Ø_fluo = 0.54) at 25 °C.¹⁸ Newly synthesized fluorophores could function as versatile feedstock for biological applications owing to high extinction coefficients (>150 nm).

Table 5 Spectral properties of fluorophores 5a–u^a

Compd	λmax (nm)	λem (nm)	ε × 10^3 (dm^3 mol^−1 cm^−1)	Øfluo^b	Stokes shift (nm)
a Measured in CHCl3 at 25 °C.b Measured with quinine sulphate in 0.1 M H2SO4 as standard.
5a	370, 266, 242	427	29.4, 100.8, 134.7	0.08	185
5b	368, 264, 228	429	16.3, 72.4, 83.9	0.07	201
5c	370, 266, 250	427	16.0, 86.6, 75.0	0.10	161
5d	370, 268, 242	428	26.1, 110.4, 103.3	0.09	160
5e	370, 264, 246	428	22.1, 79.0, 75.9	0.09	164
5f	368, 266, 241	427	20.6, 82.7, 87.1	0.08	186
5g	370, 268, 242	428	16.4, 56.4, 60.1	0.09	186
5h	228	428	79.3	0.02	200
5i	366, 268, 242	423	23.3, 89.1, 72.5	0.11	155
5j	366, 266, 242	424	4.4, 17.3, 16.0	0.08	158
5k	368, 272, 242	426	14.1, 47.0, 43.3	0.08	154
5l	370, 266, 242	429	19.1, 65.9, 68.8	0.10	187
5m	240	440	140.8	0.03	200
5n	384, 274, 242	421	50.0, 120.1, 163.9	0.13	202
		444
5o	376, 270, 242	434	12.7, 50.4, 59.3	0.05	192
5p	376, 264, 246	433	8.6, 36.0, 34.6	0.07	169
5q	378, 250	439	22.9, 71.1	0.15	189
5r	376, 274, 242	432	32.2, 98.0, 98.4	0.15	216
		458
5s	372, 268, 242	434	19.8, 88.6, 111.0	0.12	192
5t	368, 268, 248	425	21.7, 73.9, 78.9	0.06	177
5u	368, 266, 248	423	11.4, 25.5, 25.0	0.21	157

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Considering electronic effects on the 1,2,3-triazole moiety (5a–g and 5l) introduced by the substitution on the phenyl group, both electron-donating and withdrawing substituents resulted in modest quantum yields. Among the aliphatic systems (5h–k), the cyclopropyl group leading to compound 5h resulted in a prejudicial quantum yield, whereas employing an acyclic n-butyl group affording compound 5i resulted in a cumulative quantum yield. An electron donating substituent with a dimethoxy group on the quinoline fragment resulted in an improved quantum yield in comparison to electron withdrawing substituents (5o and 5p). An enhanced quantum yield was observed upon hopping to heterocyclic moieties (5q and 5r). Eventually, though an electron withdrawing (–F) substituent (5u) is present on the benzimidazole core, this molecule possessed high quantum yield of 0.21, probably due to the contribution from a lone pair of electrons on the –F substituent and presence of a rich π-electron system. Absorption and emission spectra of 5q, 5r, and 5u in CHCl₃ at 25 °C are shown in Fig. 3.

Fig. 3 Absorption and emission spectra of 5q, 5r, and 5u in CHCl₃ at 25 °C.

Conclusions

In conclusion, the present MCR deals with a facile and direct avenue to synthesize versatile 1,2,3-triazole anchored benzimidazo[1,2-a]quinolines. An ease of operation employing a dual catalytic system with low catalyst loading and PEG-400 as an environmentally benign solvent crafts this protocol to be more appealing and synthetically efficient. The domino process revealed good tolerance to various substrates affording desired products in moderate to good yields. It is apparent that click and activate approach could serve as a novel platform to engineer an immensely decorated 1,2,3-triazole anchored nitrogenous fused heterocyclic framework. The 1,2,3-triazole motif was revealed to be moderately electron withdrawing in activating the adjacent methylene linker to undergo a Knoevenagel condensation. Owing to the high extinction coefficients (>150 nm), these molecules could function as versatile feedstock for biological and fluorescent applications. As the current investigation rendered promising fluorophore properties, customization with appropriate substituents and chromophores to generate essential fluorogenic substrates is under exploration in our laboratory.

Experimental

General

Chemicals and solvents were procured from commercial sources and are analytically pure. Thin-layer chromatography (TLC) was carried out on aluminium-supported silica gel plates (Merck 60 F254) with visualization of components by UV light (254 nm).

Column chromatography was carried out on silica gel (Merck 230–400 mesh). ¹H and ¹³C NMR spectra were recorded at 400 MHz using a Bruker AV 400 spectrometer (Bruker CO., Switzerland) in CDCl₃ or DMSO-d₆ solution with tetramethylsilane as the internal standard, and chemical shift values (δ) are given in ppm. Some of the compound's ¹H and ¹³C NMR spectra were recorded by addition of 10 μL of formic acid or trifluoroacetic acid to the CDCl₃ solution due to the solubility issues. IR spectra were recorded on a FT-IR spectrometer (Shimadzu) and peaks are reported in cm⁻¹. Melting points were determined on an electro thermal melting point apparatus (Stuart-SMP30) in open capillary tubes and are uncorrected. High resolution mass spectra (HRMS) were recorded on a QSTAR XL hybrid MS/MS mass spectrometer. UV-Visible absorption spectra were recorded using a Jasco V-650 spectrophotometer and fluorescence spectra were recorded using a Jasco FP-6300 spectrofluorometer.

Experimental procedure for synthesis of substituted 2-(azidomethyl)-1H-benzo[d]imidazole.
Step 1. Substituted 2-(chloromethyl)-1H-benzo[d]imidazole was prepared according to the literature procedure.¹⁹ Substituted o-phenylenediamine (0.05 mol), chloroacetic acid (0.075 mol) and 4 N hydrochloric acid (50 mL) was heated under reflux for 45 minutes. The mixture was allowed to stand overnight, diluted with 100 mL of water, cooled and neutralized with sodium bicarbonate. The resultant solid was filtered, washed with cold water and dried over vacuum. The crude product was taken as such for step 2 without further purification.
Step 2. Substituted 2-(azidomethyl)-1H-benzo[d]imidazole was prepared according to the literature procedure.¹⁹ Substituted 2-(chloromethyl)-1H-benzo[d]imidazole (0.05 mol) and NaN₃ (0.055 mol) in DMSO (40 mL) was stirred at room temperature. The reaction was monitored by TLC. After completion, it was diluted with 100 mL of water and extracted with diethyl ether (10 mL × 3). The combined organic extracts were washed with brine, and dried over anhydrous Na₂SO₄. After the organic solvent was removed under reduced pressure, the residue was purified by column chromatography to provide the title compound.
2-(Azidomethyl)-1H-benzo[d]imidazole (1a). Off-white solid, 6.5 g 75%, mp 120–121 °C; IR ν_max (KBr) 2103, 1433, 1309, 1271, 1031, 997, 747 cm⁻¹; characterization details (¹H and ¹³C NMR) correlate with the literature reports.¹⁹
2-(Azidomethyl)-5-methyl-1H-benzo[d]imidazole (1b). Beige solid, 7.6 g 82%, mp 102–103 °C; IR ν_max (KBr) 2173, 2103, 1450, 1326, 1280, 1254, 1188, 1140, 1027, 801 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.50 (d, J = 8.2 Hz, 1H), 7.38 (s, 1H), 7.11 (dd, J = 8.4, 1.3 Hz, 1H), 4.73 (s, 2H), 2.47 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 148.64, 138.19, 137.02, 133.14, 124.67, 115.33, 114.66, 48.45, 21.81.
2-(Azidomethyl)-5-chloro-1H-benzo[d]imidazole (1c). Light brown solid, 7.4 g 72%, mp 112–113 °C; IR ν_max (KBr) 2178, 2105, 1424, 1318, 1276, 1061, 1023, 800 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.61 (s, 1H), 7.53 (d, J = 7.5 Hz, 1H), 7.30–7.26 (m, 1H), 4.79 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 149.57, 132.46, 132.28, 130.44, 127.04, 115.43, 114.39, 45.65.
2-(Azidomethyl)-5-fluoro-1H-benzo[d]imidazole (1d). Light brown solid, 6.3 g 68%, mp 81–82 °C; IR ν_max (KBr) 2186, 2101, 1445, 1328, 1256, 1139, 1027, 860, 809 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.46 (m, 1H), 7.21 (m, 1H), 6.98 (m, 1H), 4.69 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 158.62 (d, ¹J_CF = 240.38 Hz), 150.00, 138.31, 134.99, 116.04 (d, ³J_CF = 10.1 Hz), 111.59 (d, ²J_CF = 25.25 Hz), 101.21 (d, ²J_CF = 27.27 Hz), 48.39.

Experimental procedure for synthesis of 6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (4a). 2-(Azidomethyl)-1H-benzo[d]imidazole 1a (3 mmol), phenylacetylene 3a (3 mmol), CuSO₄·5H₂O (0.1 mmol), sodium ascorbate (0.2 mmol) and t-BuOH : H₂O (1 : 1, 5 mL) were added into a 10 mL round bottom flask. The reaction mixture was stirred at room temperature for 30 min. Reaction progress was monitored by TLC. After completion, the reaction mass was diluted with water (10 mL). Resultant precipitate was filtered and dried to obtain analytical pure product 4a. Colorless solid, 775 mg 94%, mp 209–210 °C; ¹H NMR (400 MHz, DMSO-d₆) δ 12.20 (s, 1H), 8.05 (s, 1H), 7.79–7.77 (d, J = 7.8 Hz, 3H), 7.42–7.38 (t, J = 7.5 Hz, 2H), 7.36–7.29 (m, 2H), 7.27–7.25 (dd, J = 5.8, 2.8 Hz, 2H), 5.89 (s, 2H); ¹³C NMR (100 MHz, DMSO-d₆) δ 147.96, 130.24, 128.70, 128.10, 125.52, 120.44, 48.03; HRMS (ESI, m/z): calcd for C₁₆H₁₄N₅ [M + H]⁺ 276.1249, found 276.1251.

Experimental procedure for synthesis of 6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5a). An oven dried 10 mL round bottom flask was charged with 2-(azidomethyl)-1H-benzo[d]imidazole 1a (1 mmol), 2-bromobenzaldehyde 2a (1 mmol), phenylacetylene 3a (1 mmol), K₂CO₃ (3 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol) and PEG-400 (2 mL). The resulting mixture was stirred at 120 °C under N₂ atmosphere. Reaction progress was monitored by TLC. After completion, the reaction mass was allowed to cool to ambient temperature, diluted with water (5 mL) and extracted with DCM (3 × 5 mL). The combined organic layer was dried with anhydrous Na₂SO₄ and evaporated to dryness. The crude material was purified by column chromatography using eluent (CHCl₃/EtOAc = 50/1) to obtain desired tandem product 5a in 93% yield (335 mg). The compounds 5b–g and 5k–u were prepared following the same protocol.

Experimental procedure for synthesis of 5h–j. An oven dried 10 mL round bottom flask was charged with 2-(azidomethyl)-1H-benzo[d]imidazole 1a (1 mmol), 2-bromo benzaldehyde 2a (1 mmol), low boiling substituted acetylene 3h–j (1 mmol), K₂CO₃ (3 mmol), CuI (0.1 mmol), picolinic acid (0.2 mmol) and PEG-400 (2 mL). The resulting mixture was stirred under N₂ atmosphere at 50 °C for 1 h before elevating the operating temperature to 120 °C for 8 h. Reaction progress was monitored by TLC. After completion, the reaction mass was allowed to cool to ambient temperature, diluted with water (5 mL) and extracted with DCM (3 × 5 mL). The combined organic layer was dried with anhydrous Na₂SO₄ and evaporated to dryness. The crude material was purified by column chromatography using eluent (CHCl₃/EtOAc = 50/1) to obtain desired tandem product 5h–j.
6-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5a). Colorless solid, 335 mg 93%, mp 216–217 °C; IR ν_max (KBr) 3033, 1538, 1453, 1397, 1245, 1202, 1016, 898, 756 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.84 (s, 1H), 8.70 (d, J = 8 Hz, 1H), 8.68 (s, 1H), 8.51 (d, J = 8.5 Hz, 1H), 8.14 (d, J = 6.9 Hz, 1H), 8.06 (t, J = 8.5 Hz, 3H), 7.90–7.83 (m, 1H), 7.69–7.56 (m, 3H), 7.52 (t, J = 7.6 Hz, 2H), 7.41 (t, J = 7.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 147.10, 138.23, 137.24, 132.76, 131.71, 130.33, 128.91, 128.16, 128.04, 127.41, 126.41, 125.93, 125.26, 124.94, 124.70, 121.19, 120.88, 120.40, 117.53, 114.92, 114.07; HRMS (ESI, m/z): calcd for C₂₃H₁₆N₅ [M + H]⁺ 362.1406, found 362.1410.
6-(4-(p-Tolyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5b). Beige solid, 342 mg 88%, mp 252–253 °C; IR ν_max (KBr) 3154, 1541, 1467, 1398, 1246, 1078, 1018, 813, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.74 (s, 1H), 8.61 (d, J = 9.6 Hz, 2H), 8.44 (d, J = 7.7 Hz, 1H), 8.10 (dd, J = 7.4, 1.4 Hz, 1H), 7.98 (dd, J = 7.9, 1.4 Hz, 1H), 7.94 (d, J = 8.1 Hz, 2H), 7.83–7.79 (ddd, J = 8.5, 7.3, 1.5 Hz, 1H), 7.63–7.53 (m, 3H), 7.34–7.29 (m, 2H), 2.43 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 147.82, 144.24, 141.58, 138.11, 134.60, 131.24, 130.46, 130.31, 129.54, 127.71, 125.97, 125.12, 124.97, 124.93, 123.74, 122.20, 121.49, 121.13, 121.02, 115.06, 114.15, 21.38; HRMS (ESI, m/z): calcd for C₂₄H₁₈N₅ [M + H]⁺ 376.1562, found 376.1569.
6-(4-(4-(tert-Butyl)phenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5c). Beige solid, 249 mg 72%, mp 216–217 °C; IR ν_max (KBr) 3055, 1541, 1467, 1395, 1245, 1199, 1075, 1015, 821, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.77 (s, 1H), 8.63 (d, J = 7.6 Hz, 2H), 8.45 (d, J = 7.6 Hz, 1H), 8.11 (m, 1H), 7.99 (dd, J = 7.4, 2.9 Hz, 3H), 7.84–7.78 (m, 1H), 7.63–7.53 (m, 5H), 1.40 (s, 9H); ¹³C NMR (100 MHz, CDCl₃) δ 151.35, 147.66, 144.12, 141.37, 134.41, 131.07, 130.30, 130.18, 127.73, 125.81, 125.78, 125.03, 124.85, 124.75, 123.66, 122.06, 121.57, 121.02, 120.72, 114.90, 114.04, 34.74, 31.37; HRMS (ESI, m/z): calcd for C₂₇H₂₄N₅ [M + H]⁺ 418.2032, found 418.2028.
6-(4-(4-Methoxyphenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5d). Beige solid, 281 mg 72%, mp 215–216 °C; IR ν_max (KBr) 3051, 1563, 1498, 1465, 1247, 1022, 818, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.71 (s, 1H), 8.64 (d, J = 8.5 Hz, 1H), 8.61 (s, 1H), 8.47 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 7.1 Hz, 1H), 8.02–7.97 (m, 3H), 7.85–7.81 (t, J = 7.9 Hz, 1H), 7.65–7.55 (m, 3H), 7.05 (d, J = 9.6 Hz, 2H), 3.89 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.78, 147.60, 144.26, 141.52, 134.69, 131.21, 130.43, 130.24, 127.36, 125.11, 124.95, 124.91, 123.73, 123.25, 122.18, 121.09, 121.00, 120.97, 115.04, 114.26, 114.15, 55.37; HRMS (ESI, m/z): calcd for C₂₄H₁₈N₅O [M + H]⁺ 392.1511, found 392.1516.
6-(4-(4-Chlorophenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5e). Colorless solid, 296 mg 81%, mp 278–279 °C; IR ν_max (KBr) 3046, 1542, 1468, 1247, 1198, 1017, 821, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.84 (s, 1H), 8.76–8.64 (m, 2H), 8.51 (d, J = 6.8 Hz, 1H), 8.14 (d, J = 7.2 Hz, 1H), 8.05 (d, J = 7.9 Hz, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.89–7.85 (t, J = 6.7 Hz, 1H), 7.65–7.59 (dd, J = 14.5, 7.0 Hz, 3H), 7.48 (d, J = 8.3 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 146.68, 136.22, 134.42, 133.31, 132.37, 132.10, 130.91, 128.37, 128.32, 128.10, 127.53, 127.37, 126.27, 125.47, 121.69, 119.64, 118.91, 115.76, 115.64, 115.03; HRMS (ESI, m/z): calcd for C₂₃H₁₅ClN₅ [M + H]⁺ 396.1016, found 396.1021.
6-(4-(4-Fluorophenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a] quinoline (5f). Beige solid, 330 mg 87%, mp 292–293 °C; IR ν_max (KBr) 3052, 1562, 1495, 1400, 1226, 1019, 827, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.81 (s, 1H), 8.70 (d, J = 8.6 Hz, 1H), 8.67 (s, 1H), 8.52 (d, J = 7.5 Hz, 1H), 8.14 (d, J = 8.9 Hz, 1H), 8.08–8.02 (m, 3H), 7.87 (t, J = 7.9 Hz, 1H), 7.68–7.58 (m, 3H), 7.23–7.18 (t, J = 8.7 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 162.06 (d, ¹J_CF = 250.48 Hz), 147.70, 138.29, 135.62, 133.64, 133.46, 131.69, 129.50, 128.50, 127.98 (d, ³J_CF = 9.09 Hz), 127.85, 127.77, 126.60, 124.44, 122.50, 120.85, 117.45, 116.39, 116.17 (d, ²J_CF = 25.25 Hz), 115.61; HRMS (ESI, m/z): calcd for C₂₃H₁₅FN₅ [M + H]⁺ 380.1311, found 380.1315.
6-(4-(4-(Trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5g). Colorless solid, 344 mg 80%, mp 283–284 °C; IR ν_max (KBr) 3054, 1620, 1541, 1397, 1254, 1114, 1015, 826, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.89 (s, 1H), 8.65 (d, J = 8.8 Hz, 2H), 8.46 (d, J = 7.7 Hz, 1H), 8.13 (d, J = 7.8 Hz, 2H), 8.09 (d, J = 5.9 Hz, 1H), 8.01 (d, J = 1.2 Hz, 1H), 7.84–7.80 (m, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.59–7.54 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 188.9, 163.9, 132.3, 131.0, 129.7, 128.9, 127.2, 126.5, 125.4, 123.8, 122.5, 121.1, 114.0, 55.6; HRMS (ESI, m/z): calcd for C₂₄H₁₅F₃N₅ [M + H]⁺ 430.1280, found 430.1278.
6-(4-Cyclopropyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5h). Pale green solid, 249 mg 77%, mp 194–195 °C; IR ν_max (KBr) 3081, 1540, 1397, 1243, 1027, 893, 813, 754 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.20 (s, 1H), 8.62 (d, J = 8.5 Hz, 1H), 8.52 (s, 1H), 8.45 (dd, J = 7.4, 1.4 Hz, 1H), 8.09 (dd, J = 7.2, 1.6 Hz, 1H), 8.00–7.95 (m, 1H), 7.84–7.77 (m, 1H), 7.63–7.54 (m, 3H), 2.20–2.11 (m, 1H), 1.08–1.04 (m, 4H); ¹³C NMR (100 MHz, CDCl₃) δ 149.08, 143.12, 140.58, 133.38, 130.08, 129.22, 129.07, 123.97, 123.80, 122.59, 121.11, 119.97, 119.84, 113.89, 113.02, 6.75, 5.89; HRMS (ESI, m/z): calcd for C₂₀H₁₆N₅ [M + H]⁺ 326.1406, found 326.1402.
6-(4-Butyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5i). Colorless solid, 242 mg 71%, mp 130–131 °C; IR ν_max (KBr) 3052, 1539, 1453, 1399, 1224, 1035, 889, 814, 756, cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.25 (s, 1H), 8.62 (d, J = 8.5 Hz, 1H), 8.54 (s, 1H), 8.45 (d, J = 8.2 Hz, 1H), 8.11–8.06 (m, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.84–7.78 (m, 1H), 7.63–7.53 (m, 3H), 2.95–2.89 (m, 2H), 1.88–1.80 (dt, J = 13.0, 7.6 Hz, 2H), 1.55–1.45 (m, 2H), 1.03–0.99 (t, J = 7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 148.43, 144.19, 141.70, 134.45, 131.16, 130.30, 130.14, 125.09, 125.03, 124.89, 123.65, 122.97, 122.21, 121.03, 120.95, 114.97, 114.11, 31.59, 25.58, 22.50, 13.93; HRMS (ESI, m/z): calcd for C₂₁H₂₀N₅ [M + H]⁺ 342.1719, found 342.1721.
6-(1H-1,2,3-Triazol-1-yl)benzimidazo[1,2-a]quinoline (5j). Pale yellow solid, 242 mg 88%, mp 212–213 °C; IR ν_max (KBr) 3059, 1544, 1466, 1395, 1252, 1216, 1078, 1010, 737 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.59 (s, 1H), 8.68 (d, J = 8.5 Hz, 1H), 8.62 (s, 1H), 8.51–8.48 (dd, J = 7.1, 1.8 Hz, 1H), 8.11–8.08 (dd, J = 7.0, 2.2 Hz, 1H), 8.04–8.01 (dd, J = 7.9, 1.2 Hz, 1H), 7.98 (d, J = 1.1 Hz, 1H), 7.88–7.83 (m, 1H), 7.64–7.58 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 144.19, 141.58, 134.57, 133.81, 131.17, 130.42, 130.38, 125.98, 125.12, 124.96, 123.75, 122.08, 121.34, 121.07, 115.02, 114.11; HRMS (ESI, m/z): calcd for C₁₇H₁₂N₅ [M + H]⁺ 286.1093, found 286.1097.
(1-(Benzimidazo[1,2-a]quinolin-6-yl)-1H-1,2,3-triazol-4-yl) methanol (5k). Beige solid, 210 mg 67%, mp 236–237 °C; IR ν_max (KBr) 3302, 3074, 1540, 1401, 1202, 1039, 848, 756 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.55 (s, 1H), 8.69 (d, J = 8.5 Hz, 1H), 8.60 (s, 1H), 8.50 (d, J = 8.5 Hz, 1H), 8.10 (d, J = 7.6 Hz, 1H), 8.03 (d, J = 7.7 Hz, 1H), 7.89–7.85 (t, J = 7.9 Hz, 1H), 7.69–7.55 (m, 3H), 5.01 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 161.32, 147.32, 139.98, 134.10, 132.70, 131.31, 130.14, 127.25, 127.07, 126.78, 126.26, 125.56, 124.64, 122.12, 118.79, 115.94, 114.94, 55.00; HRMS (ESI, m/z): calcd for C₁₈H₁₄N₅O [M + H]⁺ 316.1198, found 316.1195.
6-(4-(Pyridin-2-yl)-1H-1,2,3-triazol-1-yl)benzoimidazo[1,2-a]quinoline (5l). Beige solid, 239 mg 66%, mp 248–249 °C; IR ν_max (KBr) 3048, 1599, 1545, 1470, 1399, 1213, 1020, 789, 757, 733 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 10.12 (s, 1H), 8.75 (d, J = 4.8 Hz, 1H), 8.65 (d, J = 8.6 Hz, 1H), 8.63 (s, 1H), 8.47 (d, J = 7.6 Hz, 1H), 8.32 (d, J = 7.9 Hz, 1H), 8.13 (d, J = 7.5 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.90–7.81 (m, 2H), 7.64–7.57 (m, 3H), 7.34–7.31 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 145.49, 143.82, 143.48, 134.22, 133.39, 131.74, 130.04, 128.60, 127.80, 127.24, 126.69, 126.02, 125.88, 124.32, 122.21, 121.58, 118.38, 116.21, 115.22; HRMS (ESI, m/z): calcd for C₂₂H₁₅N₆ [M + H]⁺ 363.1358, found 363.1362.
3-Methoxy-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5m). Pale green solid, 250 mg 64%, mp 254–255 °C; IR ν_max (KBr) 3061, 1539, 1482, 1454, 1404, 1236, 1019, 806, 768, 739, 694 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.84 (s, 1H), 8.57 (s, 1H), 8.53 (d, J = 8.9 Hz, 1H), 8.40 (d, J = 8.1 Hz, 1H), 8.13–8.05 (m, 3H), 7.64–7.51 (m, 4H), 7.45–7.36 (m, 3H), 3.98 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 157.98, 148.26, 137.29, 136.14, 129.32, 129.20, 129.07, 128.10, 128.00, 127.73, 126.28, 126.02, 125.87, 123.88, 122.63, 121.23, 120.78, 117.57, 117.41, 115.13, 111.66, 55.99; HRMS (ESI, m/z): calcd for C₂₄H₁₈N₅O [M + H]⁺ 392.1511, found 392.1509.
2,3-Dimethoxy-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5n). Beige solid, 321 mg 76%, mp 280–281 °C; IR ν_max (KBr) 3064, 1536, 1468, 1389, 1270, 1017, 759 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.74 (s, 1H), 8.46 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.08–8.04 (td, J = 7.9, 0.9 Hz, 3H), 7.93 (s, 1H), 7.63–7.57 (m, 1H), 7.54–7.49 (td, J = 8.1, 4.8 Hz, 3H), 7.43–7.37 (m, 1H), 7.21 (s, 1H), 4.14 (s, 3H), 4.00 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 153.91, 148.38, 147.43, 136.16, 133.72, 128.43, 128.30, 128.15, 127.73, 127.11, 126.36, 125.05, 124.97, 119.62, 117.08, 116.27, 115.91, 114.23, 109.25, 97.23, 55.95, 55.55; HRMS (ESI, m/z): calcd for C₂₅H₂₀N₅O₂ [M + H]⁺ 422.1617, found 422.1620.
3-Chloro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5o). Beige solid, 237 mg 60%, mp 271–272 °C; IR ν_max (KBr) 3058, 1535, 1448, 1402, 1205, 1015, 796, 738, 688 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.83 (s, 1H), 8.57 (d, J = 7.7 Hz, 2H), 8.39 (m, 1H), 8.12 (m, 1H), 8.06 (dd, J = 5.2, 3.2 Hz, 2H), 7.97 (d, J = 2.4 Hz, 1H), 7.78–7.75 (dd, J = 9.1, 2.4 Hz, 1H), 7.66–7.57 (m, 2H), 7.55–7.49 (m, 2H), 7.44–7.38 (m, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 148.05, 140.58, 139.88, 132.41, 131.87, 131.80, 130.22, 129.83, 129.17, 129.11, 128.60, 126.82, 126.06, 125.37, 123.89, 123.52, 123.29, 121.84, 119.69, 116.96, 114.46; HRMS (ESI, m/z): calcd for C₂₃H₁₅ClN₅ [M + H]⁺ 396.1016, found 396.1014.
3-Fluoro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5p). Pale green solid, 337 mg 89%, mp 312–313 °C; IR ν_max (KBr) 3032, 1539, 1451, 1402, 1203, 1013, 916, 760 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.99 (s, 1H), 8.91 (s, 1H), 8.89 (d, J = 3.9 Hz, 1H), 8.65 (d, J = 8.4 Hz, 1H), 8.13 (d, J = 7.7 Hz, 1H), 7.94–7.81 (m, 4H), 7.73–7.65 (m, 2H), 7.39–7.30 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.38 (d, ¹J_CF = 252.5 Hz), 147.87, 136.17, 132.97, 128.85, 128.79, 128.31, 128.18, 126.86, 126.40, 126.07, 125.13, 123.48 (d, ³J_CF = 9.09 Hz), 121.30 (d, ²J_CF = 26.26 Hz), 120.36, 119.74, 118.09 (d, ³J_CF = 9.09 Hz), 116.05, 115.49 (d, ²J_CF = 24.24 Hz), 114.74; HRMS (ESI, m/z): calcd for C₂₃H₁₅FN₅ [M + H]⁺ 380.1311, found 380.1314.
6-(4-Phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5q). Colorless solid, 293 mg 81%, mp 315–316 °C; IR ν_max (KBr) 3050, 1530, 1449, 1200, 1014, 903, 766 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.55 (d, J = 8.0 Hz, 1H), 9.22 (d, J = 3.2 Hz, 1H), 9.14 (s, 1H), 9.11 (s, 1H), 8.77 (d, J = 7.2 Hz, 1H), 8.13 (d, J = 7.8 Hz, 1H), 7.99–7.86 (m, 3H), 7.66–7.54 (m, 2H), 7.19 (d, J = 3.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 152.24, 147.85, 142.97, 138.87, 136.46, 132.54, 128.72, 128.56, 128.21, 127.85, 126.80, 126.49, 125.25, 125.06, 123.21, 120.12, 119.54, 118.24, 116.67, 114.92; HRMS (ESI, m/z): calcd for C₂₂H₁₅N₆ [M + H]⁺ 363.1358, found 363.1355.
12-Methyl-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzo[g]benzimidazo[1,2-a][1,8]naphthyridine (5r). Green solid, 255 mg 60%, mp 316–317 °C; IR ν_max (KBr) 3045, 1610, 1534, 1476, 1402, 1208, 1015, 765 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.74 (d, J = 7.2 Hz, 1H), 9.26 (s, 1H), 9.19 (s, 1H), 9.14 (s, 1H), 8.15 (d, J = 6.8 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.98–7.94 (m, 3H), 7.79–7.72 (m, 3H), 7.50–7.44 (m, 3H), 3.06 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 148.58, 147.27, 141.43, 140.95, 138.17, 136.61, 134.17, 134.06, 129.64, 129.17, 129.00, 128.75, 128.09, 127.69, 127.55, 126.91, 126.86, 125.94, 120.46, 120.21, 118.20, 116.36, 115.22, 18.66; HRMS (ESI, m/z): calcd for C₂₇H₁₉N₆ [M + H]⁺ 427.1671, found 427.1676.
9-Methyl-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline and 10-methyl-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5s). (For regioisomeric mixture = 1 : 1) beige solid, 315 mg 84%, mp 242–243 °C; IR ν_max (KBr) 3055, 1539, 1469, 1396, 1199, 1014, 766, 692 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.83 (s, 0.5H), 9.81 (s, 0.5H), 8.66–8.58 (m, 2H), 8.32 (d, J = 8.6 Hz, 0.5H), 8.25 (s, 0.5H), 8.11–8.06 (m, 2H), 8.04–7.97 (m, 1.5H), 7.90 (s, 0.5H), 7.83 (m, 1H), 7.61–7.50 (m, 3H), 7.47–7.38 (m, 2H), 2.71 (s, 1.5H), 2.63 (s, 1.5H); ¹³C NMR (100 MHz, CDCl₃) δ 148.13, 148.04, 138.22, 136.11, 133.84, 133.55, 132.60, 132.30, 131.18, 131.10, 130.27, 129.19, 129.14, 129.09, 128.78, 128.55, 128.45, 127.92, 127.34, 126.81, 126.58, 125.99, 125.87, 125.38, 122.09, 121.80, 121.46, 121.28, 118.14, 117.81, 115.84, 114.62, 114.51, 22.27, 21.60; HRMS (ESI, m/z): calcd for C₂₄H₁₈N₅ [M + H]⁺ 376.1562, found 376.1565.
9-Chloro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline and 10-chloro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5t). (For regioisomeric mixture = 1 : 1) off white solid, 304 mg 77%, mp 278–279 °C; IR ν_max (KBr) 3057, 1539, 1395, 1201, 1017, 765 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.75 (s, 0.5H), 9.74 (s, 0.5H), 8.67 (s, 0.5H), 8.65 (s, 0.5H), 8.54 (dd, J = 16.8, 8.5 Hz, 1H), 8.45 (d, J = 1.7 Hz, 0.5H), 8.37 (d, J = 8.9 Hz, 0.5H), 8.09–8.00 (m, 4H), 7.85 (dd, J = 14.0, 6.6 Hz, 1H), 7.64–7.57 (m, 1.5H), 7.56–7.48 (m, 2.5H), 7.41 (t, J = 8.0 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 148.55, 148.52, 138.97, 138.93, 134.51, 134.46, 134.43, 133.96, 133.85, 133.13, 133.10, 132.34, 131.75, 129.82, 129.63, 129.22, 129.09, 128.14, 128.07, 127.85, 127.04, 126.02, 122.48, 122.44, 121.02, 120.93, 120.80, 120.61, 118.35, 118.33, 116.99, 116.63, 116.31, 116.27, 115.60; HRMS (ESI, m/z): calcd for C₂₃H₁₅ClN₅ [M + H]⁺ 396.1016, found 396.1019.
9-Fluoro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline and 10-fluoro-6-(4-phenyl-1H-1,2,3-triazol-1-yl)benzimidazo[1,2-a]quinoline (5u). (For regioisomeric mixture = 1 : 1) colorless solid, 250 mg 66%, mp 266–267 °C; IR ν_max (KBr) 3035, 1541, 1476, 1398, 1203, 1016, 762, 692 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 9.77 (s, 0.5H), 9.76 (s, 0.5H), 8.68 (s, 0.5H), 8.63 (s, 0.5H), 8.60 (d, J = 8.5 Hz, 0.5H), 8.49 (d, J = 8.5 Hz, 0.5H), 8.42 (dd, J = 9.2, 4.4 Hz, 0.5H), 8.17 (dd, J = 9.6, 2.3 Hz, 0.5H), 8.08–8.01 (m, 3.5H), 7.88–7.83 (m, 1H), 7.76 (dd, J = 9.0, 2.5 Hz, 0.5H), 7.61 (t, J = 7.6 Hz, 1H), 7.51 (td, J = 7.6, 1.5 Hz, 2H), 7.43–7.31 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 160 (d, ¹J_CF = 253.51 Hz), 158.98 (d, ¹J_CF = 245.43 Hz), 147.54, 140.85, 140.67, 135.95, 133.68, 133.62, 132.81, 132.54, 131.34, 131.29, 129.96, 129.84, 129.34, 129.31, 129.16, 128.34, 128.29, 126.96, 126.87, 126.78, 126.33, 126.04, 122.42, 122.08, 122.03, 121.68, 121.61, 120.03, 119.93, 116.18, 116.07, 115.92, 115.66, 115.58, 115.50, 114.21, 113.96, 104.84, 104.56, 102.19, 101.89; HRMS (ESI, m/z): calcd for C₂₃H₁₅FN₅ [M + H]⁺ 380.1311, found 380.1315.

Spectral properties

The absorption and fluorescence spectra of all compounds in liquid solutions of CHCl₃ (spectroscopic grade) at room temperature were recorded with the aid of a Jasco V-650 spectrophotometer and a Jasco FP-6300 spectrofluorometer, respectively. Fluorescence quantum yield (Ø_fluo) was determined using quinine sulphate in 0.1 M H₂SO₄ as a standard (Ø_fluo = 0.54).

Acknowledgements

KVGCS thanks DBT, New Delhi [No. BT/PR4801/MED/29/370/2012] for providing financial support. HNN is grateful to BITS-Pilani, Hyderabad Campus for providing institute fellowship. AS thanks DBT for junior research fellowship. NS thanks UGC for senior research fellowship.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Photophysical data, copies of NMR spectra for products. See DOI: 10.1039/c5ra24048d

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