One-pot three-component synthesis of 1,4,5-trisubstituted 5-iodo-1,2,3-triazoles from 1-copper(I) alkyne, azide and molecular iodine

Abstract

Copper(I)-catalyzed cycloaddition of 1-iodoalkyne and azide has proven to be the most efficient method for the synthesis of 1,4,5-trisubstituted 5-iodo-1,2,3-triazoles, but pre-made 1-iodoalkyne is required. We find that the combination of 1-copper(I) alkyne and molecular iodine can serve as a synthetic equivalent of 1-iodoalkyne. Thus, the desired 5-iodo-1,2,3-triazole can be synthesized by simply mixing this combination and an azide together without the tedious synthesis of the corresponding 1-iodoalkyne.

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Introduction

Great progress¹ has been made in the application of 1,2,3-triazoles since the discovery of the copper(I)-catalyzed cycloaddition of azide (1) and terminal alkyne (2) (CuAAC).² Normal CuAAC reactions produce only 1,4-disubstituted 1,2,3-triazole (3). Thus, the importance of 1,4,5-trisubstituted 5-iodo-1,2,3-triazole (4) has been enhanced recently because its iodine atom can be smoothly converted into various groups to give the corresponding 1,4,5-trisubstituted 1,2,3-triazoles, by which the diversity of structures and their properties could be increased (Fig. 1).^3–8

Fig. 1 5-Iodo-1,2,3-triazoles (4) as versatile substrates.

Investigation showed that two practical methods have been used for the synthesis of 5-iodo-1,2,3-triazoles (4) (Scheme 1). Method-a^4b,6c,9 is achieved easily by adding an electrophile I⁺ into a normal CuAAC reaction to trap the 5-copper(I)-1,2,3-triazole intermediate. But, this method usually gives 4 as a mixture with by-product 3 caused by the competitive substitution of the in situ generated electrophile H⁺. Method-b^4a,7a,7c,10 gives 4 as a single product by using 1-iodoalkyne (5) as a substrate under the similar conditions, but pre-made 1-iodoalkynes (5) are required.

Scheme 1 Two practical methods for the synthesis of 4.

To date, method-b has proven to be the most efficient method for the synthesis of 5-iodo-1,2,3-triazoles (4) and a total of five protocols have been reported.^4a,7a,7c,10 In these protocols, the Cu(I)-catalyzed cycloaddition of 1-iodoalkyne and azide proceeds so easily that the synthesis of the substrate 1-iodoalkyne (5) has been become a main obstacle. Herein, we would like to report a sixth protocol for the same purpose by using the combination of 1-copper(I) alkyne (6) and molecular iodine as a synthetic equivalent of 1-iodoalkyne (5). Thus, the desired 5-iodo-1,2,3-triazole (4) can be efficiently synthesized by simply mixing this combination and an azide (1) together without the tedious synthesis of the corresponding 1-iodoalkyne (5).

Results and discussion

Many protocols have been reported for the synthesis of 1-iodoalkynes (5) from terminal alkynes (2). But, only some of them could proceed under mild conditions (without using strong bases or air sensitive reagents) when the special substrates or reagents were employed.^7c,11 Furthermore, since 1-iodoalkynes (5) are sensitive to air and light, decompositions are observed during their preparation, purification and storage.¹² In our recent works, 1-iodoalkyne (5) was unexpectedly produced from the mixture of 1-Cu(I) alkyne (6) and NIS in CH₂Cl₂.¹³ As shown in Scheme 2, when we mixed together 1-Cu(I)-2-(4-methyphenyl)ethyne (6a) and I₂ in CH₂Cl₂, the desired 1-iodo-2-(4-methyphenyl)ethyne (5a) was obtained also in 98% yield within 10 min.

Scheme 2 Preparation of 1-iodoalkyne from 1-Cu(I) alkyne and I₂.

Since this conversion cleanly produced equimolar amounts of 5a and CuI only, it may be used to synthesize 1-benzyl-4-(4-methylphenyl)-5-iodo-1,2,3-trizole (4a) in the presence of benzyl azide (1a). As shown in Table 1, this hypothesis was proved and 4a was obtained in 74% yield after the mixture of 1a, 6a and I₂ in CH₂Cl₂ was stirred for 6 h (entry 1). Many solvents were suitable for this conversion and DMF gave the best results (entry 9).

Table 1 Effect of solvent on the yield of 4a^a

Entry	Solvent	Yield^b of 4a (%)
a The mixture of 1a (0.75 mmol), 6a (0.5 mmol) and I2 (0.5 mmol) in solvent (1 mL) was stirred in a stoppered glass tube. b The isolated yields.
1	CH2Cl2	74
2	THF	20
3	PhCH3	25
4	EtOH	43
5	CH3CN	58
6	CH3COCH3	72
7	ClCH2CH2Cl	75
8	NMP	87
9	DMF	90

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Further experiments proved that the yield of 4a was influenced significantly by the reactant ratios. As shown in Table 2, the yield of 4a was increased by the increase of the ratio of 1a (entries 1–4). No comparable changes were observed by using higher ratio of 6a (entry 5–6). However, the yield of 4a was decreased sharply by the increase of the ratio of I₂ (entries 7–9). Since 1,4-di(4-methylphenyl)butadiyne [(4-MePhC≡C)₂] was separated in these entries, the problem must be caused by the oxidizing property of I₂, by which the in situ generated 1-iodoalkyne 5a underwent a Cu(I)-catalyzed oxidative coupling. The other two popular precursors of I⁺, NIS and ICl, were tested also under the similar conditions, but lower yields of 4a and higher yields of oxidative coupling byproduct were obtained.

Table 2 Effect of the substrate ratio on the yield of 4a^a

Entry	1a : 6a : I2 (by mole)	Yield^b of 4a (%)
a The mixture (0.5 mmol scale) of 1a, 6a and I2 in DMF (1 mL) was stirred in a stoppered glass tube. b The isolated yields.
1	1.0 : 1.0 : 1.0	81
2	1.2 : 1.0 : 1.0	86
3	1.5 : 1.0 : 1.0	90
4	2.0 : 1.0 : 1.0	90
5	1.5 : 1.2 : 1.0	89
6	1.5 : 1.5 : 1.0	88
7	1.5 : 1.0 : 1.2	53
8	1.5 : 1.0 : 1.5	29
9	1.5 : 1.0 : 2.0	10

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In the early references, the vital role of ligand in Cu(I)-catalyzed cycloaddition of 1-iodoalkynes (5) has been reported. For example, Rutjes¹⁴ reported that the mixture of 1-iodoalkyne (5), azide (1) and CuI failed to give the cycloaddition product in the absence of ligand. But, the similar cycloaddition was reported by Fokin^7c to give 5-iodo-1,2,3-triazole (4) in excellent yields in the presence of 2 equiv. of Et₃N. Therefore, four popular ligands L1–L4 were tested as shown in Table 3. When 2 equiv. of Et₃N (L1) were added to the reaction, 4a was obtained in 80% yield within 15 min (entry 2). The similarly efficient result was obtained also when 0.3 equiv. of Et₃N (L1) was employed (entry 4). The all results in Table 3 indicated that the use of ligand could significantly enhance the reaction rate, but the yield of 4a was decreased and the coupling product (4-MePhC≡C)₂ was only by-product. This may result from the fact that 6a was activated by dissociating its polymeric structures with Et₃N.^15b–d,17a Therefore, the activated 6a underwent two by-reactions to give the by-product: (a) the oxidative coupling between two molecules of 6a; (b) the Castro–Stephens coupling between 6a and the in situ produced 5a. Finally, the entry 4 was assigned as our standard conditions.

Table 3 Effects of the ligands L1–L4 on the reaction^a

Entry	L (equiv.)	Time	Yield^b of 4a (%)
a The mixture of 1a (0.75 mmol), 6a (0.5 mmol) and I2 (0.5 mmol) in DMF (1 mL) was stirred in a stoppered glass tube. b The isolated yields.
1	None	6 h	90
2	L1 (2.0)	15 min	80
3	L1 (0.5)	15 min	79
4	L1 (0.3)	15 min	82
5	L1 (0.2)	1.5 h	79
6	L1 (0.1)	4 h	82
7	L2 (0.3)	15 min	73
8	L3 (0.3)	1 h	70
9	L4 (0.3)	4 h	75

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So far, we successfully developed a one-pot three-component method for the synthesis of 1,4,5-trisubsituted 5-iodo-1,2,3-triazoles. In fact, this similar ideal has been attempted by Fokin,^7c but it failed possibly because the catalytically active complex was disrupted either through oxidation of the metal or displacement/destruction of the ligand. However, there were no such problems in our method for three possible reasons. (a) Molecular iodine (a weak electrophile with the lowest oxidizability) was used as the resource of I⁺ because 1-Cu(I) alkyne (6) has strong nucleophilicity. (b) A clean metathesis between 1-Cu(I) alkyne (6) and I₂ occurred without use of any additive and formation of any waster, in which the quantitatively formed 1-iodoalkyne (5) and CuI are the essential substrate and catalyst, respectively. (c) The in situ formed stoichiometric amount of Cu(I) was used as a catalyst, by which the catalytic cycle of Cu(I) was unnecessary.

Thus, the success of our method is mainly due to the use of 1-Cu(I)-alkyne (6) as a substrate. It is well known that most 1-Cu(I)-alkyne (6) can be easily prepared as yellow crystals within 1 h (ref. 15, 16d and 17b) and can be stored in air for years without notable decomposition.^15–17 Therefore, it is synthetically convenient and valuable to use the combination of 1-Cu(I)-alkyne (6) and I₂ as a synthetic equivalent of 1-iodoalkyne (5), by which no needs of preparation, purification and storage of 1-iodoalkyne (5).

Finally, the scope of substrates and products were tested to generalize this method. As shown in Scheme 3, two yields obtained from two different procedures were reported for each product to meet the different needs. Most products were synthesized in good to excellent yields by both procedures. Compared with the procedure with ligand, the ligand-free procedure gave the higher yields, but the longer reaction time was required. The product 4q was obtained in the lowest yield may be caused by its poor solubility. It quickly crystallized from DMF once it formed even though the double amounts of DMF were used, by which some of unreacted 1-Cu(I)-alkynes (6h) were wrapped.

Scheme 3 The scope of the method.

Conclusions

A “one-pot” three-component method for the synthesis of 1,4,5-trisubsituted 5-iodo-1,2,3-triazoles was developed from 1-Cu(I) alkyne, azide and I₂. In this method, the combination of 1-Cu(I) alkyne and I₂ is well served as a synthetic equivalent of 1-iodoalkyne without need of tedious preparation, purification and storage of 1-iodoalkyne.

Experimental

General information

All melting points were determined on a Yanaco melting point apparatus and were uncorrected. IR spectra were recorded as KBr pellets on a Nicolet FT-IR 5DX spectrometer. All spectra of ¹H NMR (400 MHz) and ¹³C NMR (100 MHz) were recorded on a JEOL JNM-ECA 400 spectrometer in CDCl₃ (otherwise as indicated). TMS was used as an internal reference and J values are given in Hz. HRMS were obtained on a Bruker micrOTOF-Q II spectrometer. Copper(I) alkynes 6a–6k were prepared by reported procedure in literature.^15,16d,17b

A typical procedure for the preparation of 1-benzyl-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4a). Procedure A with a ligand. To a stirred suspension of 1-copper(I)-2-(4-methyl-phenyl)ethyne (6a, 89.4 mg, 0.5 mmol) in DMF (1 mL) in a glass tube was added BnN₃ (1a, 99.9 mg, 0.75 mmol), I₂ (126.9 mg, 0.5 mmol) and Et₃N (15.2 mg, 0.15 mmol) successively at room temperature. After 15 min, the resultant mixture was subjected to a flash chromatography [silica gel, 10% EtOAc in petroleum ether (60–90 °C)] to give 153 mg (82%) of product 4a as a white solid.

Procedure B without a ligand. To a stirred suspension of copper(I)-2-(4-methylphenyl)ethyne (6a, 89.4 mg, 0.5 mmol) in DMF (1 mL) in a glass tube was added BnN₃ (1a, 99.9 mg, 0.75 mmol) and I₂ (126.9 mg, 0.5 mmol) successively at room temperature. After 6 h [the end-point was indicated by the fact that the in situ generated (4-methylphenyl)ethynyl iodide (5a) was exhausted], the resultant mixture was subjected to a flash chromatography [silica gel, 10% EtOAc in petroleum ether (60–90 °C)] to give 167 mg (90%) of product 4a as a white solid, mp 110–112 °C (lit.^7c 119–120 °C). ¹H NMR (400 MHz, CDCl₃) δ 7.83 (d, J = 8.2 Hz, 2H), 7.38–7.29 (m, 5H), 7.26 (d, J = 7.8 Hz, 2H), 5.66 (s, 2H), 2.39 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.2, 138.5, 134.3, 129.2 (2C), 128.8 (2C), 128.4, 127.8 (2C), 127.3 (3C), 76.1, 54.3, 21.3.

The products 4b–4v were prepared similarly by this procedure.

1-Benzyl-4-(2-methylphenyl)-5-iodo-1,2,3-triazole (4b). Light yellow solid (124 mg, 66%), mp 108–110 °C. IR v 3028, 2950, 2856, 1607, 1502, 1458, 1217 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.40–7.29 (m, 8H), 7.25–7.22 (m, 1H), 5.66 (s, 2H), 2.29 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 152.2, 137.7, 134.4, 130.6, 130.5, 129.8, 129.2, 129.0 (2C), 128.6, 127.9 (2C), 125.5, 79.7, 54.4, 20.3. HRMS (ESI-TOF) (m/z): calcd for C₁₆H₁₄IN₃, [M + H]⁺ 376.0305; found 376.0293.

1-Benzyl-4-(4-methoxyphenyl)-5-iodo-1,2,3-triazole (4c). White solid (139 mg, 71%), mp 116–118 °C (lit.¹⁸ 114–115 °C). ¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J = 7.3 Hz, 2H), 7.36–7.29 (m, 5H), 6.98 (d, J = 7.4 Hz, 2H), 5.65 (s, 2H), 3.84 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.8, 150.1, 134.4, 128.8 (2C), 128.7 (2C), 128.4, 127.8 (2C), 122.7, 113.9 (2C), 75.6, 55.3, 54.3.

1-Benzyl-4-phenyl-5-iodo-1,2,3-triazole (4d). White solid (144 mg, 80%), mp 136–138 °C (lit.^8a 138.7–140.3 °C). ¹H NMR (400 MHz, CDCl₃) δ 7.94 (d, J = 7.8 Hz, 2H), 7.45–7.30 (m, 8H), 5.67 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 150.1, 134.3, 130.2, 128.9 (2C), 128.6, 128.5 (2C), 128.4, 127.8 (2C), 127.4 (2C), 76.4, 54.3.

1-Benzyl-4-(4-fluorophenyl)-5-iodo-1,2,3-triazole (4e). White solid (154 mg, 81%), mp 142–143 °C (lit.^8a 150.8–152.0 °C). ¹H NMR (400 MHz, CDCl₃) δ 7.93–7.90 (m, 2H), 7.39–7.30 (m, 5H), 7.16–7.12 (m, 2H), 5.66 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 162.9 (d, J_CF = 247.9 Hz), 149.4, 134.2, 129.3 (d, J_CF = 8.6 Hz, 2C), 128.9 (2C), 128.5, 127.8 (2C), 126.3, 115.5 (d, J_CF = 21.0 Hz, 2C), 76.2, 54.4.

1-Benzyl-4-(4-chlorophenyl)-5-iodo-1,2,3-triazole (4f). White solid (168 mg, 85%), mp 135–137 °C (lit.^7b no melting point was reported). ¹H NMR (400 MHz, CDCl₃) δ 7.89 (d, J = 8.7 Hz, 2H), 7.42 (d, J = 8.7 Hz, 2H), 7.39–7.30 (m, 5H), 5.66 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 149.1, 134.5, 134.1, 128.9 (2C), 128.8 (2C), 128.7, 128.6 (2C), 128.5, 127.8 (2C), 76.4, 54.4.

1-Benzyl-4-(4-bromophenyl)-5-iodo-1,2,3-triazole (4g). White solid (194 mg, 88%), mp 136–138 °C (lit.^7b no melting point was reported). ¹H NMR (400 MHz, CDCl₃) δ 7.83 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.7 Hz, 2H), 7.39–7.30 (m, 5H), 5.66 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 149.2, 134.1, 131.7 (2C), 129.1, 128.9 (2C), 128.8 (2C), 128.5, 127.8 (2C), 127.7, 76.4, 54.4.

1-Benzyl-4-(4-nitrophenyl)-5-iodo-1,2,3-triazole (4h). Yellow solid (162 mg, 80%), mp 126–128 °C. IR v 3042, 1595, 1514, 1451, 1340 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.31 (d, J = 9.2 Hz, 2H), 8.20 (d, J = 9.2 Hz, 2H), 7.40–7.32 (m, 5H), 5.70 (s, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 147.9, 147.5, 136.5, 133.8, 129.0 (2C), 128.7, 127.8 (2C), 127.7 (2C), 123.8 (2C), 77.7, 54.6. HRMS (ESI-TOF) (m/z): calcd for C₁₅H₁₁IN₄O₂, [M + H]⁺ 407.0000; found 407.0002.

1-Benzyl-5-iodo-1,2,3-triazole-4-carboxylic acid ethyl ester (4i). White solid (148 mg, 83%), mp 141–143 °C (lit.¹⁰ no melting point was reported). ¹H NMR (400 MHz, CDCl₃) δ 7.35–7.33 (m, 3H), 7.28–7.26 (m, 2H), 5.67 (s, 2H), 4.44 (q, J = 7.3 Hz, 2H), 1.43 (t, J = 7.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 160.2, 142.2, 133.5, 128.9 (2C), 128.7, 127.8 (2C), 84.6, 61.5, 54.4, 14.2.

1-Benzyl-4-cyclohexyl-5-iodo-1,2,3-triazole (4j). Light yellow solid (171 mg, 93%), mp 104–106 °C. IR v 3032, 2929, 2848, 1608, 1492, 1442, 1215 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.35–7.30 (m, 3H), 7.28–7.23 (m, 2H), 5.56 (s, 2H), 2.64–2.56 (m, 1H), 1.86–1.81 (m, 4H), 1.75–1.67 (m, 3H), 1.41–1.26 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 156.0, 134.6, 128.8 (2C), 128.3, 127.7 (2C), 76.9, 53.9, 36.0, 31.9 (2C), 26.4 (2C), 25.8. HRMS (ESI-TOF) (m/z): calcd for C₁₅H₁₈IN₃, [M + H]⁺ 368.0618; found 368.0613.

1-Benzyl-4-cyclopropyl-5-iodo-1,2,3-triazole (4k). Light yellow solid (145 mg, 89%), mp 103–105 °C (lit.^7c 114–116 °C). ¹H NMR (400 MHz, CDCl₃) δ 7.36–7.30 (m, 3H), 7.29–7.24 (m, 2H), 5.54 (s, 2H), 1.80–1.74 (m, 1H), 1.06–1.02 (m, 2H), 1.00–0.94 (m, 2H); ¹³C NMR (100 MHz, CDCl₃) δ 153.2, 134.5, 128.8 (2C), 128.3, 127.7 (2C), 77.6, 54.0, 7.5 (2C), 7.2.

1-(4-Methylbenzyl)-4-(4-fluorophenyl)-5-iodo-1,2,3-triazole (4l). Light yellow solid (138 mg, 70%), mp 170–172 °C. IR v 3029, 2924, 2852, 1604, 1530, 1472, 1229 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.92–7.89 (m, 2H), 7.23–7.11 (m, 6H), 5.62 (s, 2H), 2.33 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 162.8 (d, J_CF = 247.0 Hz), 149.4, 138.4, 131.2, 129.5 (2C), 129.3 (d, J_CF = 8.6 Hz, 2C), 127.8 (2C), 126.4, 115.5 (d, J_CF = 21.0 Hz, 2C), 76.1, 54.2, 21.1. HRMS (ESI-TOF) (m/z): calcd for C₁₆H₁₃FIN₃, [M + H]⁺ 394.0211; found 394.0207.

1-(4-Fluorobenzyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4m). Light yellow solid (161 mg, 82%), mp 128–130 °C. IR v 3036, 2918, 2860, 1605, 1506, 1471, 1222 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.82 (d, J = 8.2 Hz, 2H), 7.33–7.25 (m, 4H), 7.06–7.01 (m, 2H), 5.62 (s, 2H), 2.39 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 162.7 (d, J_CF = 245.7 Hz), 150.3, 138.6, 130.1 (d, J_CF = 3.8 Hz), 129.8 (d, J_CF = 8.4 Hz, 2C), 129.2 (2C), 127.3 (2C), 127.2, 115.9 (d, J_CF = 22.1 Hz, 2C), 75.9, 53.6, 21.3. HRMS (ESI-TOF) (m/z): calcd for C₁₆H₁₃FIN₃, [M + H]⁺ 394.0211; found 394.0206.

1-(4-Bromobenzyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4n). Light yellow solid (177 mg, 78%), mp 157–159 °C. IR v 3027, 2935, 2856, 1584, 1478, 1228 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J = 7.8 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.2 Hz, 2H), 5.60 (s, 2H), 2.39 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.4, 138.6, 133.3, 132.1 (2C), 129.5 (2C), 129.2 (2C), 127.3 (2C), 127.1, 122.6, 76.0, 53.7, 21.3. HRMS (ESI-TOF) (m/z): calculated for C₁₆H₁₃BrIN₃, [M + H]⁺ 453.9410; found 453.9408.

1-(4-Methoxylbenzyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4o). White solid (152 mg, 75%), mp 121–123 °C. IR v 3015, 2929, 2840, 1610, 1510, 1442, 1245 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J = 7.4 Hz, 2H), 7.29–7.24 (m, 4H), 6.86 (d, J = 7.8 Hz, 2H), 5.57 (s, 2H), 3.78 (s, 3H), 2.38 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.6, 150.2, 138.4, 129.4 (2C), 129.1 (2C), 127.3, 127.2 (2C), 126.4, 114.2 (2C), 75.8, 55.2, 53.9, 21.3. HRMS (ESI-TOF) (m/z): calculated for C₁₇H₁₆IN₃O, [M + H]⁺ 406.0411; found 406.0403.

1-(4-Methylbenzyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4p). Light yellow solid (169 mg, 87%), mp 116–118 °C. IR v 3026, 2917, 2860, 1615, 1510, 1472, 1222 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.82 (d, J = 8.2 Hz, 2H), 7.26–7.14 (m, 6H), 5.61 (s, 2H), 2.39 (s, 3H), 2.33 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.2, 138.4, 138.3, 131.3, 129.5 (2C), 129.2 (2C), 127.8 (2C), 127.3, 127.2 (2C), 76.0, 54.1, 21.3, 21.1. HRMS (ESI-TOF) (m/z): calcd for C₁₇H₁₆IN₃, [M + H]⁺ 390.0462; found 390.0463.

1-(4-Nitrobenzyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4q). Light yellow solid (84 mg, 40%), mp 190–192 °C. IR v 3020, 2920, 2860, 1607, 1535, 1346, 1224 cm⁻¹; ¹H NMR (400 MHz, DMSO-d₆) δ 8.26 (d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.2 Hz, 2H), 7.46 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 5.91 (s, 2H), 2.35 (s, 3H); ¹³C NMR (100 MHz, DMSO-d₆) δ 150.2, 148.1, 143.8, 138.8, 130.1 (2C), 129.4 (2C), 128.4, 127.7 (2C), 124.9 (2C), 82.6, 53.7, 21.8. HRMS (ESI-TOF) (m/z): calcd for C₁₆H₁₃IN₄O₂, [M + H]⁺ 421.0156; found 421.0152.

1-(2-Naphthylmethyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4r). White solid (119 mg, 56%), mp 154–156 °C. IR v 3049, 2922, 2860, 1726, 1507, 1437, 1227 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.85–7.78 (m, 5H), 7.73 (s, 1H), 7.50–7.46 (m, 2H), 7.41 (d, J = 8.2 Hz, 1H), 7.25 (d, J = 7.8 Hz, 2H), 5.80 (s, 2H), 2.38 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 150.3, 138.5 (2C), 133.1, 133.0, 131.7, 129.2, 128.8, 127.9, 127.7, 127.3 (3C), 127.1, 126.5, 126.4, 125.1, 76.1, 54.5, 21.3. HRMS (ESI-TOF) (m/z): calcd for C₂₀H₁₆IN₃, [M + H]⁺ 426.0462; found 426.0458.

1-(α-Methylbenzyl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4s). White solid (88 mg, 45%), mp 144–146 °C. IR v 3023, 2994, 2931, 2861, 1611, 1480, 1448, 1217 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J = 7.8 Hz, 2H), 7.36–7.29 (m, 5H), 7.26–7.24 (m, 2H), 5.78 (q, J = 7.2 Hz, 1H), 2.38 (s, 3H), 2.10 (d, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 149.7, 140.2, 138.4, 129.1 (2C), 128.8 (2C), 128.2, 127.5 (2C), 127.4, 126.6 (2C), 76.6, 61.4, 22.3, 21.3. HRMS (ESI-TOF) (m/z): calcd for C₁₇H₁₆IN₃, [M + H]⁺ 390.0462; found 390.0466.

1-(Oct-1-yl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4t). Light yellow solid (179 mg, 90%), mp 72–74 °C. IR v 3038, 2920, 2856, 1641, 1510, 1460, 1225 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.82 (d, J = 7.8 Hz, 2H), 7.27 (d, J = 7.8 Hz, 2H), 4.42 (t, J = 7.3 Hz, 2H), 2.40 (s, 3H), 1.98–1.91 (m, 2H), 1.38–1.28 (m, 10H), 0.88 (t, J = 6.9 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 149.7, 138.3, 129.2 (2C), 127.5, 127.3 (2C), 75.8, 50.9, 31.7, 29.9, 29.0, 28.9, 26.4, 22.6, 21.3, 14.0. HRMS (ESI-TOF) (m/z): calcd for C₁₇H₂₄IN₃, [M + H]⁺ 398.1088; found 398.1085.

1-(3-Methylbut-1-yl)-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4u). White solid (163 mg, 92%), mp 83–85 °C. IR v 3035, 2950, 2920, 2861, 1641, 1514, 1460, 1255 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J = 7.8 Hz, 2H), 7.27 (d, J = 7.8 Hz, 2H), 4.44 (t, J = 7.8 Hz, 2H), 2.40 (s, 3H), 1.84 (q, J = 6.9 Hz, 2H), 1.73–1.66 (m, 1H), 1.01 (d, J = 8.3 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 149.7, 138.3, 129.2, 127.5 (2C), 127.3 (2C), 76.7, 49.4, 38.6, 25.6, 22.3 (2C), 21.3. HRMS (ESI-TOF) (m/z): calcd for C₁₄H₁₈IN₃, [M + H]⁺ 356.0618; found 356.0616.

1-Cycylohexyl-4-(4-methylphenyl)-5-iodo-1,2,3-triazole (4v). Light yellow solid (138 mg, 75%), mp 156–158 °C. IR v 3035, 2923, 2853, 1611, 1510, 1450, 1225 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 7.81 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 7.8 Hz, 2H), 4.41–4.34 (m, 1H), 2.39 (s, 3H), 2.12–1.95 (m, 6H), 1.79–1.76 (m, 1H), 1.52–1.26 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 149.1, 138.2, 129.1 (2C), 127.6, 127.5 (2C), 75.8, 61.1, 32.7 (2C), 25.4 (2C), 25.0, 21.3. HRMS (ESI-TOF) (m/z): calcd for C₁₅H₁₈IN₃, [M + H]⁺ 368.0618; found 368.0618.

Acknowledgements

This work was supported by the National Natural Scientific Foundation of China (nos 21472107, 21372142 and 21072112).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: ¹H and ¹³C NMR spectra for products 4a–4v. See DOI: 10.1039/c4ra15980b

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