Synthesis of functionalized 1,2,3-triazoles using Bi₂WO₆ nanoparticles as efficient and reusable heterogeneous catalyst in aqueous medium

Abstract

Synthesis of functionalized triazoles is reported via Bi₂WO₆ nanoparticle (10 mol%) mediated 1,3-dipolar cycloaddition reactions of β-nitrostyrenes, phenylacetylene and chalcones with azides (80 °C, 2–6 h) in water. The regioselective formation of 1,4-disubstituted triazoles was achieved in 5–20 minutes using azides and alkynes in presence of CuSO₄·5H₂O (2 mol%), sodium ascorbate (10 mol%) and Bi₂WO₆ nanoparticles (10 mol%) at room temperature in water. Similarly, regioselective synthesis of 1,4,5-trisubstituted triazoles was achieved from chalcones in aqueous medium.

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1,2,3-Triazole is an important scaffold for organic, medicinal and materials chemistry. Huisgen 1,3-dipolar cycloaddition and copper mediated azide-alkyne cycloaddition (CuAAC, Click reaction) have contributed tremendously for the construction of 1,2,3-triazoles.^1,2 Subsequently, many alternative catalysts and conditions such as Cu-based nanomaterials,³ solid supported copper,⁴ Cu-based NHC complexes,⁵ organometallic complexes⁶ ionic liquids,⁷ microwave,⁸ solvent free⁹ and metal free¹⁰ conditions etc. have been developed for the click reaction. Recently, Ramachary et al., developed the [3 + 2] cycloaddition of aldehydes and ketones via cascade/push–pull, enamine and enolate mechanisms under organocatalytic conditions.^11a,b Similar to this Wang^11c,d Bressy,^11e and Márcio^11f groups independently explored the organocatalysis for the synthesis of functionalized 1,2,3-triazoles using ketones (simple and α,β-unsaturated), and alkyledine melanonitriles. Dehaen,¹² Wang and Pan groups¹³ reported the 1,3-dipolar cycloaddition reactions of nitro alkanes, β-nitrostyrenes and chalcones using morpholine/PTSA and Ce(OTf)₃. However, some of these reports use organic solvent or require prolonged times for completion of the reaction. Considering the importance of 1,2,3-triazoles and in continuation with our interest in heterogeneous catalysis in aqueous medium,¹⁴ here in we report the application of Bi₂WO₆ nanoparticles as heterogeneous catalyst for the 1,3-dipolar cycloadditions of azides with β-nitrostyrenes, chalcones and phenylacetylene.

Thus, β-nitrostyrene (1) was reacted with benzylazide (2) in presence of Bi₂WO₆ nanoparticles (30 mol%) in water at room temperature (20 h) to give only trace amounts of the desired triazoles 3 and 4. When the same reaction mixture was heated at 80 °C for 5 h the products 3 and 4 were obtained in 95% and 5% yields (Scheme 1). After confirming the structures of the isomeric products,¹⁵ simultaneous experiments were conducted by varying solvent, reaction temperature and catalyst loading, (entries 1–9) along with the catalyst recyclability studies (entries 10–13) as shown in the Table 1.

Scheme 1 Reaction of β-nitrostyrene (1) with benzyl azide (2) in presence of 30 mol% of catalyst (Bi₂WO₆).

Table 1 Optimization of the reaction conditions (solvent, catalyst loading, temperature) and catalyst recyclability

S. no	Solvent	Temp. (°C)	Reaction time (h)	Catalyst loading (mol%)	Isolated yield^a (%) ratio of 3 : 4
a Total yield of products 3 and 4.b Cycle-1.c Cycle-2.d Cycle-3.e Cycle-4.
1	Water	RT	20	30	Trace
2	DMF	RT	20	30	—
3	DMSO	RT	20	30	—
4	Toluene	50	10	30	50
5	Water	50	10	30	70
6	Water	80	5	30	95 : 5
7	Water	80	5	20	95 : 5
8	Water	80	5	10	95 : 5
9	Water	80	5	5	85 : 3
10	Water	80	5	10	95 : 5^b
11	Water	80	5	10	93 : trace^c
12	Water	80	5	10	90 : trace^d
13	Water	80	5	10	85 : trace^e

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Table 1 indicates the success of the reactions with 10 mol% catalyst (entry 8). Thus, different β-nitrostyrenes were treated with benzylazide (2) and phenylazide (5) using 10 mol% of catalyst to give 1,5-disubstituted triazoles 8–22 (Scheme 2) in good to excellent yields as shown in (Fig. 1). Further, to explore the reactivity of Bi₂WO₆ nanoparticles, different β-nitrostyrenes were reacted with NaN₃ under optimized conditions to give the 1H-1,2,3-triazoles 23–28 in 75–90% yields (Scheme 3). To confirm the reaction pathway, separate experiments were performed using phenylacetylene (29) as coupling partner. Thus, the reaction of benzylazide (2) and phenyl acetylene (29) in presence of Bi₂WO₆ (10 mol%) at 80 °C for 2.5 h in water gave the triazoles (3 and 4) in 25% and 75% yields respectively. In a similar experiment, benzylbromide (30) and NaN₃ were treated with phenylacetylene (29) to give the desired triazoles (3 and 4) in 1 : 3 ratios as shown in Scheme 4. In order to achieve better selectivity, the classical copper-mediated click reaction was attempted in presence of Bi₂WO₆. Thus, different alkynes were treated with benzylazide (2) in presence of CuSO₄·5H₂O (2 mol%), sodium ascorbate (10 mol%) and Bi₂WO₆ (10 mol%) in aqueous medium at room temperature (Scheme 5). It was observed that the reaction went for completion within 5-20 min giving the 1,4-disubstituted triazoles (4, 7, 33–35) in 90–99% as single isomers. This remarkable activity of Bi₂WO₆ is due to presence of acidic and basic sites which are helping for the success of the reaction as shown in Fig. 2.

Scheme 2 Reactions of β-nitrostyrene (1) with benzyl azide (2) and phenylazide (5) under optimized conditions.

Fig. 1 Different triazole derivatives (8–22) prepared from β-nitrostyrenes and azides (2 and 5).

Scheme 3 Preparation of unsubstituted triazole using β-nitrostyrene, NaN₃ and Bi₂WO₆ nanoparticle (10 mol%).

Scheme 4 Preparation of disubstituted triazoles 3 and 4 using phenylacetylene (29).

Scheme 5 Bi₂WO₆-supported Click reaction (CuAAC) reaction of different alkynes and benzylazide (2) and phenylazide (5).

Fig. 2 Plausible reaction mechanism for the Bi₂WO₆ nanoparticles-mediated Click reaction.

Since the reaction is giving the quantitative yield of triazole (4), attempts were made to test the recyclability of entire catalyst system [i.e. Bi₂WO₆ + CuSO₄·5H₂O + sodium ascorbate in water] by adding organic solvent to the reaction mixture to isolate desired product and leaving the catalyst system in aqueous layer. This recovered catalyst was reused up to 5 cycles for the same reaction without much loss in the catalytic activity (Table 2). This recyclable catalytic activity was also supported by the XRD data of the catalyst which indicate no changes in the morphology even after 5 cycles (see ESI†). Based on the observations, a plausible mechanism is proposed as shown in Fig. 2. From the mechanism we assume that the (WO₄)²⁻ layers of Bi₂WO₆ nanoparticle abstract the terminal proton from phenyl acetylene. The resulting carbanion gets coordinated with (Bi₂O₂)²⁺ layer giving the bismuth-acetylide species which then undergoes transmetallation with Cu¹⁺ (generated by sodium ascorbate from Cu²⁺) to form Cu-acetylide. This can react with the azide via [3 + 2]-cyclo addition followed by the protonation of the metal–carbon bond to give the desired 1,2,3-triazole in a regiospecific manner.

Table 2 Recyclability of the catalyst system (Bi₂WO₆ + CuSO₄·5H₂O + sod. ascorbate in water) for the formation of triazole (4)

S. no.	No of cycle	Reaction time	Isolated yield (%) (min)
1	1	5	99
2	2	5	99
3	3	7	96
4	4	10	95
5	5	10	95

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Later, attention was focused towards the synthesis of functionalized triazoles using chalcones. Thus, chalcone (36) was reacted with azides (2) or (5) under optimized conditions Scheme 6. However, it was observed that the formation of the desired triazoles (37, 39) as minor products along with the enaminones (38, 40). This type of reactivity is known to involve cycloaddition-ring cleavage-rearrangement sequence.^16a The improved yield of desired triazole 37, was achieved up to 85% by performing solvent dependent reactions using water and toluene as combination as shown in Table 3. Though the enaminones are forming as by-products, these can be used for the functionalized heterocyclic molecules.^16b Considering this, different chalcones treated with azides 2 and 5 using water and toluene as reaction medium to obtain functionalized enaminones 41–51 and triazoles 52–62 (Fig. 3). For achieving better selectivity in the cycloaddition of chalcones with azides in water, the classical click conditions were attempted as described earlier. Thus, reaction of chalcones and benzylazide (2) in presence of CuSO₄·2H₂O (2 mol%), sodium ascorbate (10 mol%) and Bi₂WO₆ (10 mol%) at 80 °C for 6 h gave the tri-substituted triazoles as single isomers in 85–95% yields (Scheme 7). Further applications of these methods on complex examples are in progress in our laboratory.

Scheme 6 Reaction of chalcone 36 with benzyl and phenyl azides in water.

Table 3 Solvent controlled experiments for the formation of enaminone (38) and triazole (37)

S. no.	Water (%)	Toluene (%)	Enaminone (%)	Triazole (%)
1	90	10	90	07
2	80	20	85	12
3	70	30	75	22
4	60	40	68	29
5	50	50	50	47
6	25	75	23	75
7	—	100	10	85

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Fig. 3 Different enaminones (41–51) and triazole (52–62) derivatives.

Scheme 7 Bi₂WO₆-supported cycloaddition reaction of chalcones and benzylazide (2).

In conclusion, we have demonstrated the use of Bi₂WO₆ nanoparticles as highly effective and reusable catalyst for the 1,3-dipolar cycloaddition reactions of β-nitrostyrenes, phenylacetylene and chalcones with azides. The regioselective formation of 1,4-disubstituted triazoles was achieved for the first time in very short time (5–20 min) using combination of click reaction (CuAAC) and Bi₂WO₆ nanoparticles at room temperature in water. Similarly functionalized triazoles were prepared from chalcones under similar conditions in aqueous medium.

Acknowledgements

BP thanks MHRD, New Delhi for the fellowship. SN thanks UGC-New Delhi for the fellowship. DK thank MHRD (New Delhi), Director, NITW and DST (SERB), New Delhi for the financial support in the form of Research Seed Grant and Start-Up Research Grant (Young Scientists). PV and SK thank DST-New Delhi for the financial support.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra09544a

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