N²-selective alkylation of NH-1,2,3-triazoles with vinyl ethers via gold catalysis

Abstract

A new method was developed to synthesize N²-alkyl-substituted 1,2,3-triazoles via gold catalyzed alkylation of vinyl ethers with mono- and unsubstituted NH-1,2,3-triazoles and benzotriazole. A hydrogen bond between the oxygen atom of the vinyl ethers, activated via the gold catalyst, and the NH-1,2,3-triazoles was supposed to be generated, which selectively gave the N²-alkylation products.

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Introduction

Substituted 1,2,3-triazoles are among the most important N-heterocyclic compounds and display a broad spectrum of applications in the areas of medicinal chemistry, agrochemicals, and materials science.¹ 1,2,3-Triazoles containing heterocyclic compounds serve as intermediates for the synthesis of biologically active compounds.² Both thermal and Cu(I)/Ru(II)- catalyzed condensations of alkynes and azides provide an excellent approach to N¹-substituted triazoles.³ However, the synthesis of N²-substituted triazoles remains a challenge.^4,5 A particularly interesting subset of these compounds are N²-alkyl-1,2,3-triazoles, which possess a broad spectrum of antiherpetic, antiarrhythmic and antiviral activities.⁶ Ideally, the most direct route to N²-alkyl-1,2,3-triazoles involves nucleophilic substitution of alkylating reactants with NH-1,2,3-triazoles, however, a mixture of the isomeric products is often produced.⁷ Recently, the N²-selective alkylation reactions of alkyl halides with 1,2,3-triazoles have been achieved by incorporating C-4- and C-5-substituents on the heteroarenes, of which the synthetic utility was thus restricted by the substrate's steric requirements. Another route to the N²-alkyl-1,2,3-triazoles, addition of 1-sulfonyl-1,2,3-triazoles to olefins or vinyl ethers catalyzed by TsOH or gold catalyst, was reported by Chen and our group.⁸ Very recently, Chen and co-workers reported the highly N²-selective alkylation reactions of NH-1,2,3-triazoles with olefins mediated by NIS,⁹ in which the favored N¹-type intermolecular hydrogen bonding connection during the transition state provides the coupling adduct with a high N²-selectively (Scheme 1a). Based on our previous report of gold catalyzed N² alkylation of 1-sulfonyl-1,2,3-triazoles with vinyl ethers,^8b we hope to extend this reaction involving the use of NH-1,2,3-triazoles as nucleophiles, in which the hydrogen bond between the oxygen atom of vinyl ethers activated via gold catalyst with NH-1,2,3-triazoles produces N²-alkyl-1,2,3-triazoles (Scheme 1b).

Scheme 1 N² alkylation of NH-1,2,3-triazoles.

Results and discussion

Based on our previous results with respect to the N²-selective gold-catalyzed alkylation of 1-sulfonyl-1,2,3-triazoles,^8b we began our studies by exploring the reaction between NH-1,2,3-triazole (1a) and vinyl ether (2a). The optimization results are summarized in Table 1. To our delight, the desired N²-alkyl-1,2,3-triazole 3a was obtained in 95% yield in the presence of Ph₃PAuCl (5 mol%)/AgNTf₂ (5 mol%) in 1,2-dichloroethane (DCE) at 80 °C, without a N¹-coupling adduct (Table 1, entry 1). In order to optimize the reaction conditions, different silver salts were screened, of which Ph₃PAuCl/AgNTf₂ was found to be the best silver combination (Table 1, entries 2 and 3). The catalyst ligands were then evaluated. The N-heterocyclic carbene ligand IPrAuCl showed moderate activity, while the phosphine ligand JohnphosAuCl was not favored in this transformation, affording 3a in only 30% yield (Table 1, entries 4 and 5). Further solvent optimization identified DCE to be the best reaction medium (Table 1, entries 6–9). The addition of 4 Å molecular sieves resulted in a decreased conversion into 3a in 69% yield after 22 hours (Table 1, entry 10), due to the possible gold catalyst poisons contained in molecular sieves.¹⁰ Variation of the number of equivalents of 2a from 3.0 to 2.0 lowed the conversion of 3a to 65% (Table 1, entry 11), which indicates that the excess of vinyl ether probably is necessary due to the high tendency of vinyl ethers to undergo cationic polymerization initiated by gold(I).¹¹ Decreasing the catalyst loading to 2 mol% led to reduced reaction yield of 72% (Table 1, entry 12). In the control experiments, employing Ph₃PAuCl and AgNTf₂ separately gave none of the desired product (Table 1, entries 12 and 13) even after 24 hours.

Table 1 Condition optimization for the reaction of 1a with 2a^a

Entry	Cat. (mol%)	Solvent	Time (h)	Yield^b (%)
a Unless noted, all reactions were carried out at the 0.1 mmol scale in 3 mL solvent with the addition of 5 mol% catalyst (1a/2a = 1/3) at 80 °C, NR = no reaction.b Isolated yield.c 100 mg 4 Å MS was added.d 2 Equiv. 2a was added.e No consumption of starting material 1a was seen after 24 h.
1	Ph3PAuCl/AgNTf2 (5)	DCE	6	95
2	Ph3PAuCl/AgOTf (5)	DCE	6	81
3	Ph3PAuCl/AgSbF6 (5)	DCE	6	75
4	IPrAuCl/AgNTf2 (5)	DCE	6	79
5	JohnphosAuCl/AgNTf2 (5)	DCE	6	30
6	Ph3PAuCl/AgNTf2 (5)	DCM	6	34
7	Ph3PAuCl/AgNTf2 (5)	CHCl3	6	24
8	Ph3PAuCl/AgNTf2 (5)	CH3CN	6	60
9	Ph3PAuCl/AgNTf2 (5)	Toluene	6	71
10^c	Ph3PAuCl/AgNTf2 (5)	DCE	22	69
11^d	Ph3PAuCl/AgNTf2 (5)	DCE	24	65
12	Ph3PAuCl/AgNTf2 (2)	DCE	24	72
13^e	Ph3PAuCl (5)	DCE	24	NR
14^e	AgNTf2 (5)	DCE	24	NR

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With the optimized reaction conditions in hand, we examined the scope of this transformation by synthesizing a series N²-alkyl-1,2,3-triazoles. As shown in Table 2, various NH-1,2,3-triazoles were explored by using vinyl ether 2a as the reactants. First, various 4-aryl substituted NH-1,2,3-triazoles were explored. The NH-1,2,3-triazoles containing electron-donating functional groups, such as methyl, t-butyl, and methoxy, at the para position of the aromatic ring gave comparably good yields (80–87%) of the desired N²-alkyl-1,2,3-triazoles. However, 4-halogen phenyl substituted NH-1,2,3-triazoles gave the corresponding products in moderate yields, in which the more electron deficient triazole rings reduced their nucleophilicities. The reaction of 2-thienyl substituted NH-1,2,3-triazoles went smoothly, affording 3h in 77% yield. Moreover, 4-alkyl substituted NH-1,2,3-triazoles 1i and unsubstituted NH-1,2,3-triazole 1j could also provide the corresponding N²-alky-substituted 1,2,3-triazoles 3i and 3j in moderate yields. Benzotriazole 1k was also tested, giving 3k in 89% yield.

Table 2 Variation of the NH-1,2,3-triazoles 1^a,b

a Unless noted, all reactions were carried out at the 0.1 mmol scale in 3 mL solvent with the addition of 5 mol% catalyst (1/2a = 1/3) at 80 °C.b Isolated yield.

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We next set out to explore the scope of vinyl ethers 2 in the presence of 4-phenyl substituted 1,2,3-triazol 1a (Table 3). First, cyclic vinyl ether 2,3-dihydrofuran 2b worked very well, giving 4b in 74% yield. Next, we investigated the linear vinyl ether's reactions. We found that mono-substituted and 1,2-disubstituted linear vinyl ether could be employed in this reaction and gave the desired products in good yields. Moreover, 1,1-disubstituted vinyl ether 2j could also provide the desired N²-alkyl-1,2,3-triazole 4j in 77% yield. This reaction was also efficient with alpha-angelica lactone, giving 4k in 93% yield.

Table 3 Variation of the vinyl ethers 2^a,b

a Unless noted, all reactions were carried out at the 0.1 mmol scale in 3 mL solvent with the addition of 5 mol% catalyst (1a/2 = 1/3) at 80 °C.b Isolated yield.

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In order to understand the mechanism for the regioselective synthesis of N²-alkyl-1,2,3-triazoles, we performed two control experiments. First, we replaced vinyl ether with 4-tert-butylstyrene in the model reaction, no product was obtained. This may be due to the lower complexation of olefin with gold (Scheme 2(1)). Then, we performed this reaction in the presence of phenylacetylene, N¹-vinyl substituted 1,2,3-triazole 7 was obtained in 70% yield, which was in accordance with our previous report (Scheme 2(2)).¹² The two control experiments suggested that the N²-regioselectivity may be induced by the substrate vinyl ethers in this reaction.

Scheme 2 Control experiments.

Based on our experimental results and precedents in the literature, a proposed catalytic cycle for the N²-selective alkylation is presented in Scheme 3. Initial complexation of gold could occur via pathway A^8a or B.¹³ Pathway A shows a one-step process involving the nucleophilic attack of the internal nitrogen of the NH-1,2,3-triazole 1a on Au(I)-coordinated vinyl ether 2a through the hydrogen bond interaction to form the alkyl gold intermediate. This subsequently undergoes protodemetalation¹⁴ giving the N²-alkyl-1,2,3-triazole 3a. Pathway B shows a two-step process invoking a triazole–Au complex, which then activated vinyl ether and subsequently undergoes N²-selective alkylation with the internal nitrogen of the NH-1,2,3-triazole 1a to give the alkyl gold intermediate. This subsequently undergoes protodemetalation¹⁴ giving the N²-alkyl-1,2,3-triazole 3a. However, pathway B might be unfavorable because the N²-vinyl substituted 1,2,3-triazole could not be observed in our control experiment (Scheme 2(2)).

Scheme 3 Proposed catalytic cycle for the N²-selective alkylation.

Conclusions

In summary, we have developed a new method to synthesis N²-alkyl-1,2,3-triazoles through gold catalyzed alkylation of vinyl ethers with NH-1,2,3-triazoles. The reaction is facile, high yielding and regioselective. The regioselectivity may be induced by the hydrogen bond between the oxygen atom of vinyl ethers with NH-1,2,3-triazole. The potential utilization and extension of this interesting synthetic methodology are currently underway.

Experimental

General methods

All reactions were performed using Schlenk-tubes, septa, and syringes under nitrogen atmosphere. Commercial reagents were used as supplied or purified by standard techniques where necessary. Column chromatography was performed using 200–300 mesh silica with the proper solvent system according to TLC analysis using KMnO₄ stain and UV light to visualize the reaction components. Unless otherwise noted, nuclear magnetic resonance spectra were recorded on a Agilent 400 MHz spectrometer using CDCl₃ with TMS as internal reference at room temperature. NMR data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet and bs = broad singlet), coupling constant in Hz and integration. Chemical shifts for ¹³C NMR spectra were recorded in parts per million from tetramethylsilane using the central peak of deuterochloroform (77.0 ppm) as the internal standard. Melting points were determined on a WRS-1B digital melting point instrument. IR spectra were obtained on Nicoletisso FTIR using KBr disks. HR-MS spectral were determined on a Bruker Daltonics Bio TOF mass spectrometer. NH-1,2,3-triazoles 1a–1m were prepared according to the published methods.¹⁴ Vinyl ethers were obtained commercially and used without further purification.

General procedure for synthesis of compound 3a

To a Schlenk tube charged with nitrogen was added Ph₃PAuCl/AgNTf₂ (5 mol%) in dry DCE (3 mL). After three minutes, NH-1,2,3-triazole 1a (0.1 mmol), vinyl ether 2a (0.3 mmol) were added to the reaction. Then the reaction mixture was stirred at 80 °C for 6 h until complete consumption of starting material as monitored by TLC. Concentration of the reaction mixture in vacuo followed by purification through flash chromatography on silica gel column (hexane/EtOAc = 30/1) afforded N²-alkyl-substituted 1,2,3-triazole 3a.

4-Phenyl-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3a). The spectroscopic data are in accordance with those reported.^8b

Yield: 21.8 mg (95%); yellow oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3475, 2951, 1611, 1391, 1063 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.92 (s, 1H), 7.82 (d, J = 7.7 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.35 (t, J = 6.9 Hz, 1H), 5.75 (d, J = 8.8 Hz, 1H), 4.08 (d, J = 11.3 Hz, 1H), 3.77 (t, J = 10.4 Hz, 1H), 2.52–2.45 (m, 1H), 2.15–2.10 (m, 2H), 1.74–1.72 (m, 2H), 1.69–1.63 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 148.1, 131.5, 130.1, 128.8, 128.5, 126.1, 89.1, 67.5, 29.4, 24.7, 21.8.

2-(Tetrahydro-2H-pyran-2-yl)-4-(p-tolyl)-2H-1,2,3-triazole (3b). The spectroscopic data are in accordance with those reported.^8b

Yield: 19.4 mg (80%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3466, 2955, 1645, 1398, 1070 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.89 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 5.73 (dd, J = 9.3, 2.4 Hz, 1H), 4.08 (d, J = 11.4 Hz, 1H), 3.80–3.73 (m, 1H), 2.54–2.44 (m, 1H), 2.38 (s, 3H), 2.17–2.08 (m, 2H), 1.78–1.72 (m, 2H), 1.68–1.62 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 148.2, 138.5, 131.4, 129.5, 127.2, 125.9, 89.1, 77.3, 29.4, 24.8, 21.9, 21.3.

4-(4-(tert-Butyl)phenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3c). The spectroscopic data are in accordance with those reported.^8b

Yield: 22.8 mg (80%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3470, 2970, 1644, 1490, 1092 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.88 (s, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.3 Hz, 2H), 5.77–5.70 (m, 1H), 4.06 (d, J = 11.4 Hz, 1H), 3.76 (t, J = 9.7 Hz, 1H), 2.51–2.43 (m, 1H), 2.14–2.08 (m, 2H), 1.75–1.71 (m, 2H), 1.67–1.62 (m, 1H), 1.33 (s, 9H). ¹³C NMR (100 MHz, CDCl₃): δ 151.7, 148.1, 131.5, 127.3, 125.9, 125.7, 89.1, 67.5, 34.7, 31.3, 29.4, 24.8, 21.9.

4-(4-Methoxyphenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3d). The spectroscopic data are in accordance with those reported.^8b

Yield: 22.6 mg (87%); yellow oil liquid; R_f = 0.10 (hexane–EtOAc, 10 : 1). IR (neat): 3467, 2954, 1631, 1396, 1058 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.83 (s, 1H), 7.73 (d, J = 8.5 Hz, 2H), 6.94 (d, J = 8.7 Hz, 2H), 5.71 (dd, J = 9.5, 2.6 Hz, 1H), 4.06 (d, J = 11.5 Hz, 1H), 3.83 (s, 3H), 3.74 (t, J = 11.2, 1H), 2.50–2.43 (m, 1H), 2.14–2.07 (m, 2H), 1.75–1.70 (m, 2H), 1.68–1.63 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 159.9, 148.0, 131.1, 127.4, 122.8, 114.2, 89.1, 67.5, 55.3, 29.4, 24.8, 21.9.

4-(4-Fluorophenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3e). The spectroscopic data are in accordance with those reported.^8b

Yield: 13.8 mg (56%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3477, 2959, 1617, 1397, 1094 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.86 (s, 1H), 7.80–7.75 (m, 2H), 7.10 (t, J = 8.6 Hz, 2H), 5.72 (dd, J = 9.1, 2.0 Hz, 1H), 4.06 (d, J = 11.4 Hz, 1H), 3.75 (t, J = 10.7 Hz, 1H), 2.49–2.42 (m, 1H), 2.13–2.07 (m, 2H), 1.74–1.71 (m, 2H), 1.68–1.63 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 162.9 (d, J = 246.5 Hz), 147.3, 131.3, 127.9 (d, J = 8.2 Hz), 126.4, 115.8 (d, J = 21.6 Hz), 89.2, 67.5, 29.4, 24.8, 21.9.

4-(4-Chlorophenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3f). The spectroscopic data are in accordance with those reported.^8b

Yield: 16.8 mg (64%); yellow oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3475, 2971, 1645, 1393, 1093 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.90 (s, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.2 Hz, 2H), 5.77–5.72 (m, 1H), 4.08 (d, J = 11.8 Hz, 1H), 3.79 (d, J = 9.9 Hz, 1H), 2.51–2.43 (m, 1H), 2.16–2.09 (m, 2H), 1.77–1.72 (m, 2H), 1.69–1.66 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 147.1, 134.4, 131.5, 129.0, 128.7, 127.3, 89.2, 67.5, 29.4, 24.8, 21.8.

4-(4-Bromophenyl)-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3g). The spectroscopic data are in accordance with those reported.^8b

Yield: 17.7 mg (76%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3470, 2948, 1645, 1387, 1066 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.93 (s, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H), 5.79–5.74 (m, 1H), 4.10 (d, J = 11.7 Hz, 1H), 3.79 (d, J = 9.9 Hz 1H), 2.53–2.45 (m, 1H), 2.18–2.12 (m, 2H), 1.78–1.71 (m, 2H), 1.72–1.67 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 147.1, 131.9, 131.5, 129.1, 127.6, 122.6, 89.2, 67.5, 29.4, 24.8, 21.8.

2-(Tetrahydro-2H-pyran-2-yl)-4-(thiophen-2-yl)-2H-1,2,3-triazole (3h). The spectroscopic data are in accordance with those reported.^8b

Yield: 18.1 mg (77%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3470, 2951, 1648, 1392, 1075 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.80 (s, 1H), 7.64 (d, J = 1.4 Hz, 1H), 7.47 (d, J = 5.0 Hz, 1H), 7.39–7.34 (m, 1H), 5.71 (dd, J = 9.0, 1.9 Hz, 1H), 4.06 (d, J = 11.4 Hz, 1H), 3.74 (t, J = 10.6 Hz, 1H), 2.49–2.42 (m, 1H), 2.13–2.06 (m, 2H), 1.74–1.72 (m, 2H), 1.69–1.63 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 144.3, 131.7, 131.5, 126.4, 126.0, 122.0, 89.1, 67.5, 29.4, 24.8, 21.9.

4-Butyl-2-(tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3i). Yield: 15.1 mg (72%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3464, 2931, 1658, 1266, 1092 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.36 (s, 1H), 5.55 (dd, J = 9.5, 1.6 Hz, 1H), 3.98 (d, J = 11.6 Hz, 1H), 3.65 (t, J = 10.7 Hz, 1H), 2.62 (t, J = 7.8 Hz, 2H), 2.33 (dd, J = 20.2, 9.8 Hz, 1H), 2.00 (t, J = 14.0 Hz, 2H), 1.68–1.52 (m, 5H), 1.31 (dd, J = 14.9, 7.4 Hz, 2H), 0.86 (t, J = 7.3 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 149.3, 133.2, 88.8, 67.6, 31.2, 29.4, 25.2, 24.8, 22.3, 22.1, 13.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₁H₂₀N₃O⁺: 210.1601; found: 210.1599.

2-(Tetrahydro-2H-pyran-2-yl)-2H-1,2,3-triazole (3j). Yield: 9.3 mg (61%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3454, 2954, 1661, 1358, 1095 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.68 (s, 2H), 5.73 (d, J = 9.1 Hz, 1H), 4.04 (d, J = 11.5 Hz, 1H), 3.77–3.71 (m, 1H), 2.48–2.39 (m, 1H), 2.09–2.06 (m, 2H), 1.73–1.65 (m, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 134.6, 88.9, 67.4, 29.4, 24.7, 21.8. HRMS (ESI): m/z [M + H]⁺ calcd for C₇H₁₂N₃O⁺: 154.0975; found: 154.0968.

2-(Tetrahydro-2H-pyran-2-yl)-2H-benzo[d][1,2,3]triazole (3k). Yield: 18.1 mg (89%); colorless oil liquid; R_f = 0.10 (hexane–EtOAc, 10 : 1). IR (neat): 3467, 2940, 1664, 1274, 1086 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 8.07 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.3 Hz, 1H), 7.49 (t, J = 7.6 Hz, 1H), 7.38 (t, J = 7.7 Hz, 1H), 6.04 (dd, J = 8.2, 2.7 Hz, 1H), 3.95 (dd, J = 11.7, 4.6 Hz, 1H), 3.83–3.75 (m, 1H), 2.68–2.57 (m, 1H), 2.23–2.19 (m, 1H), 1.90–1.71 (m, 4H) ¹³C NMR (100 MHz, CDCl₃): δ 127.4, 124.1, 119.9, 111.1, 85.6, 66.8, 29.3, 24.9, 21.6. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₁H₁₄N₃O⁺: 204.1131; found: 204.1130.

4-Phenyl-2-(tetrahydrofuran-2-yl)-2H-1,2,3-triazole (4b). The spectroscopic data are in accordance with those reported.^8b

Yield: 15.9 mg (74%); colorless oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3474, 2979, 1645, 1381, 1074 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.97 (s, 1H), 7.89 (d, J = 7.4 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.45 (t, J = 7.3 Hz, 1H), 6.43 (dd, J = 6.7, 2.3 Hz, 1H), 4.30 (dd, J = 14.1, 7.6 Hz, 1H), 4.16 (dd, J = 14.0, 7.7 Hz, 1H), 2.83–2.76 (m, 1H), 2.59–2.48 (m, 2H), 2.25–2.16 (m, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 148.0, 131.4, 130.3, 128.8, 128.5, 126.0, 92.3, 69.6, 31.4, 24.5.

2-(1-Ethoxyethyl)-4-phenyl-2H-1,2,3-triazole (4c). The spectroscopic data are in accordance with those reported.^8b

Yield: 19.5 mg (90%); colorless oil liquid; R_f = 0.40 (hexane–EtOAc, 10 : 1). IR (neat): 3466, 3001, 1650, 1357, 1125 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 8.07 (s, 1H), 7.98 (d, J = 7.1 Hz, 2H), 7.59 (t, J = 7.4 Hz, 2H), 7.51 (t, J = 7.4 Hz, 1H), 5.96 (q, J = 6.0 Hz, 1H), 3.75–3.68 (m, 1H), 3.58–3.50 (m, 1H), 2.00 (d, J = 6.0 Hz, 3H), 1.32 (t, J = 7.0 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 147.8, 131.3, 130.3, 128.8, 128.5, 126.0, 89.5, 64.6, 20.9, 14.7.

2-(1-Isopropoxyethyl)-4-phenyl-2H-1,2,3-triazole (4d). The spectroscopic data are in accordance with those reported.^8b

Yield: 20.3 mg (88%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3473, 2972, 1649, 1375, 1118 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 8.02 (s, 1H), 7.95 (d, J = 7.1 Hz, 2H), 7.55 (t, J = 7.5 Hz, 2H), 7.47 (t, J = 7.4 Hz, 1H), 6.03 (q, J = 6.0 Hz, 1H), 3.87–3.77 (m, 1H), 1.94 (d, J = 6.0 Hz, 3H), 1.36 (d, J = 6.1 Hz, 3H), 1.07 (d, J = 6.2 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 147.7, 131.2, 130.3, 128.8, 128.5, 126.0, 87.4, 70.4, 22.7, 21.4, 21.3.

2-(1-Butoxyethyl)-4-phenyl-2H-1,2,3-triazole (4e). The spectroscopic data are in accordance with those reported.^8b

Yield: 19.4 mg (79%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3475, 2956, 1634, 1381, 1129 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.89 (s, 1H), 7.81 (d, J = 7.1 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 5.77 (q, J = 6.0 Hz, 1H), 3.49 (dt, J = 9.2, 6.7 Hz, 1H), 3.31 (dt, J = 9.4, 6.6 Hz, 1H), 1.82 (d, J = 6.0 Hz, 3H), 1.53–1.45 (m, 2H), 1.33–1.24 (m, 2H), 0.83 (t, J = 7.4 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 147.8, 131.2, 130.3, 128.8, 128.5, 126.0, 89.7, 68.9, 31.2, 20.8, 19.1, 13.7.

2-(1-Isobutoxyethyl)-4-phenyl-2H-1,2,3-triazole (4f). The spectroscopic data are in accordance with those reported.^8b

Yield: 19.6 mg (80%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3468, 2959, 1648, 1381, 1126 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.89 (s, 1H), 7.81 (d, J = 7.1 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 5.76 (q, J = 6.0 Hz, 1H), 3.26 (dd, J = 9.2, 6.9 Hz, 1H), 3.08 (dd, J = 9.2, 6.6 Hz, 1H), 1.82 (d, J = 6.0 Hz, 3H), 1.78 (dd, J = 13.4, 6.7 Hz, 1H), 0.85 (d, J = 6.7 Hz, 3H), 0.80 (d, J = 6.7 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 147.7, 131.2, 130.4, 128.8, 128.5, 126.0, 89.9, 75.8, 28.2, 20.8, 19.2, 19.1.

2-(1-(Cyclohexyloxy)ethyl)-4-phenyl-2H-1,2,3-triazole (4g). The spectroscopic data are in accordance with those reported.^8b

Yield: 19.3 mg (71%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3465, 2948, 1644, 1383, 1102 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.88 (s, 1H), 7.81 (d, J = 7.1 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 5.93 (q, J = 6.0 Hz, 1H), 3.40–3.34 (m, 1H), 2.00–1.98 (m, 1H), 1.80 (d, J = 6.0 Hz, 3H), 1.71–1.70 (m, 1H), 1.63–1.56 (m, 1H), 1.48–1.33 (m, 3H), 1.23–1.10 (m, 4H). ¹³C NMR (100 MHz, CDCl₃): δ 147.7, 131.1, 130.4, 128.8, 128.5, 126.0, 87.2, 76.2, 32.7, 31.4, 25.5, 24.0, 23.9, 21.4.

2-(1-Ethoxypropyl)-4-phenyl-2H-1,2,3-triazole (4h). The spectroscopic data are in accordance with those reported.^8b

Yield: 17.1 mg (74%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3465, 2963, 1650, 1381, 1107 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.90 (s, 1H), 7.82 (d, J = 7.1 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.4 Hz, 1H), 5.52 (t, J = 6.7 Hz, 1H), 3.57–3.50 (m, 1H), 3.43–3.36 (m, 1H), 2.21 (p, J = 7.4 Hz, 2H), 1.15 (t, J = 7.0 Hz, 3H), 0.88 (t, J = 7.5 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 147.9, 131.3, 130.3, 128.8, 128.5, 126.0, 94.5, 64.7, 28.0, 14.7, 9.0.

2-(1-Ethoxybutyl)-4-phenyl-2H-1,2,3-triazole (4i). The spectroscopic data are in accordance with those reported.^8b

Yield: 21.6 mg (88%); colorless oil liquid; R_f = 0.50 (hexane–EtOAc, 10 : 1). IR (neat): 3469, 2962, 1647, 1381, 1112 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.89 (s, 1H), 7.81 (d, J = 7.2 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 5.60 (t, J = 6.7 Hz, 1H), 3.57–3.49 (m, 1H), 3.43–3.35 (m, 1H), 2.19–2.147 (m, 2H), 1.45–1.35 (m, 1H), 1.28–1.21 (m, 1H), 1.15 (t, J = 7.0 Hz, 3H), 0.93 (t, J = 7.4 Hz, 3H). ¹³C NMR (100 MHz, CDCl₃): δ 147.8, 131.3, 130.3, 128.8, 128.5, 126.0, 93.0, 64.7, 36.7, 18.0, 14.7, 13.5.

2-(2-Ethoxypropan-2-yl)-4-phenyl-2H-1,2,3-triazole (4j). Yield: 16.7 mg (77%); colorless oil liquid; R_f = 0.30 (hexane–EtOAc, 10 : 1). IR (neat): 3442, 2940, 1661, 1384, 1072 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.92 (s, 1H), 7.84 (d, J = 7.2 Hz, 2H), 7.44 (t, J = 7.5 Hz, 2H), 7.37 (d, J = 7.4 Hz, 1H), 3.10 (s, 3H), 1.98 (s, 6H). ¹³C NMR (100 MHz, CDCl₃): δ 147.5, 131.0, 128.8, 128.4, 126.0, 93.0, 50.8, 25.7. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₂H₁₆N₃O⁺: 218.1288; found: 218.1289.

5-Methyl-5-(4-phenyl-2H-1,2,3-triazol-2-yl)dihydrofuran-2(3H)-one (4k). The spectroscopic data are in accordance with those reported.^8b

Yield: 22.6 mg (93%); yellow oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3465, 2978, 1740, 1635, 1380 cm⁻¹. ¹H NMR (400 MHz, DMSO): δ 8.43 (s, 1H), 7.87 (d, J = 7.2 Hz, 2H), 7.46 (t, J = 7.4 Hz, 2H), 7.39 (t, J = 7.3 Hz, 1H), 3.09–2.96 (m, 2H), 2.84–2.75 (m, 1H), 2.68–2.60 (m, 1H), 2.14 (s, 3H). ¹³C NMR (100 MHz, DMSO): δ 176.0, 148.4, 133.2, 129.8, 129.5, 129.4, 126.4, 97.9, 33.7, 29.2, 25.1.

4-Phenyl-1-(1-phenylvinyl)-1H-1,2,3-triazole (7). The spectroscopic data are in accordance with those reported.¹²

Yield: 17.2 mg (70%); yellow oil liquid; R_f = 0.20 (hexane–EtOAc, 10 : 1). IR (neat): 3038, 2934, 1496, 1459, 756 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ 7.99–7.97 (m, 2H), 7.93 (s, 1H), 7.60–7.45 (m, 8H), 6.00 (d, J = 1.0 Hz, 1H), 5.69 (d, J = 0.9 Hz, 1H). ¹³C NMR (100 MHz, CDCl₃): δ 147.6, 143.0, 134.6, 130.2, 129.9, 128.9, 128.8, 128.3, 127.4, 125.8, 119.8, 109.4.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was financially supported by the Project of Science and Technology Department of Sichuan Province (No. 2018JY0319) and the Fundamental Research Funds of Central Universities, Southwest Minzu University (2018NZD05).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c8ra04790a

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