Synthesis method of acetenyl-containing 1, 2, 3-triazole derivative

Abstract

The invention belongs to the field of organic synthesis, and relates to a synthesis method of an ethynyl-containing 1, 2, 3-triazole derivative. Synthesis method of 4-TMS-ethynyl-1, 2, 3-triazole derivative with structure shown in formula I and synthesis method of 5-TMS-ethynyl-1, 2, 3-triazole derivative with structure shown in formula III: # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing ethynyl-containing 1,2,3-triazole derivatives. Background Art

[0002] As a precursor in many drug syntheses and organic reactions, terminal alkynes are one of the key groups in organic molecules, which are mainly used for synthesizing bioactive compounds, polymers, and new materials. On the other hand, 1,2,3-triazole, as a five-membered heterocycle, exhibits many advantages in the fields of drugs and materials. Especially after click chemistry was widely accepted, the synthesis and application of compounds containing 1,2,3-triazole structures have received further extensive attention, and multiple drugs containing 1,2,3-triazole structural fragments are in clinical trials. Ethynyl-containing 1,2,3-triazoles have broad application potential. Such ethynyl-containing 1,2,3-triazoles include ethynyl structures at the C4 and C5 positions, namely 4-ethynyl-1,2,3-triazole and 5-ethynyl-1,2,3-triazole respectively.

[0003] Regarding 1,2,3-triazoles containing ethynyl structures, the current synthesis methods are very limited. Although various methods have achieved the synthesis of 1,2,3-triazole structures containing alkynyl groups, these methods are not applicable to the synthesis of ethynyl-1,2,3-triazoles. Due to the special nature of this structure, in 2010, Jesus M. Aizpurua in the Netherlands developed a method for preparing 4-ethynyl-1,2,3-triazole using 1,2,3-triazole-4-carbaldehyde as a raw material. This reaction requires prefabricating 4-formyl-1,2,3-triazole from 1,2,3-triazole-4-methanol, and then converting the aldehyde group into an ethynyl group in the presence of the reagent dimethyl (1-diazo-2-oxopropyl)phosphonate, thereby achieving the preparation of compounds containing 4-ethynyl-1,2,3-triazole structures. This reagent is relatively expensive. Another synthesis method is to carry out a click reaction between mono(trimethylsilyl)butadiyne and a compound containing an azide functional group, thereby achieving the synthesis of 4-ethynyl-1,2,3-triazole structures. In this synthesis, mono(trimethylsilyl)butadiyne needs to be prepared by single desilylation of bis(trimethylsilyl)butadiyne using a methyl lithium-lithium bromide complex, which increases the cost of the reaction and the complexity of the operation. On the other hand, as an isomer of 4-ethynyl-1,2,3-triazole, currently, these synthesis methods are not suitable for the synthesis of 5-ethynyl-1,2,3-triazole structural compounds, and at the same time, there is no mature method for synthesizing 5-ethynyl-1,2,3-triazole structures. Therefore, directly synthesizing ethynyl-containing 1,2,3-triazole structures has important value.

[0004] The present invention realizes a method for synthesizing 1,2,3-triazole containing ethynyl group. Specifically, it realizes respectively the assembly of ethynyl group or trimethylsilylethynyl group only at the C4 position on the 1,2,3-triazole ring, and the assembly of ethynyl group or trimethylsilylethynyl group only at the C5 position. Summary of the Invention

[0005] The present invention provides a method for synthesizing 4-TMS-ethynyl-1,2,3-triazole derivative with the structure of formula I, which is characterized by including the following steps:

[0006]

[0007] In an organic solvent, bis(trimethylsilyl)butadiyne reacts with the azide derivative with the structure of formula II under the action of a copper salt and an additive to obtain the 4-TMS-ethynyl-1,2,3-triazole derivative with the structure of formula I; wherein R1 is selected from C1-C3 alkyl, phenyl optionally substituted simultaneously by one or more phenyl, halophenyl, pyridyl, benzoyl, C1-C3 alkoxy, halogen; the copper salt is selected from monovalent copper salts or complexes of monovalent copper salts, and the monovalent copper salt is preferably one or more mixtures selected from cuprous chloride, cuprous bromide, cuprous iodide; the additive is selected from nitrogen-containing ligands or phosphorus-containing ligands, and is preferably one or more mixtures selected from triethylamine, pyridine, tetramethylethylenediamine (TMEDA), diisopropylethylamine, triphenylphosphine, 2,2'-bipyridine, N,N-dimethylaminopyridine (DMAP), 1,10-phenanthroline. The molar dosage of bis(trimethylsilyl)butadiyne is 1.0-2.0 times (preferably 1.2-1.5 times) that of the compound of formula II, the molar dosage of the copper salt is 0.05-0.1 times that of the compound of formula II, and the molar dosage of the additive is 0.5-2.0 times (preferably 1.0-1.5 times) that of the compound of formula II. The organic solvent is a conventional reaction solvent in the art, and those skilled in the art can reasonably select according to the reaction characteristics and the properties of the reactants, such as dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, hexamethylphosphoramide, dioxane, methyl tert-butyl ether, 2-methylfuran, and preferably N,N-dimethylformamide, N,N-dimethylacetamide (DMA), tetrahydrofuran.

[0008] Another embodiment of the present invention provides a method for synthesizing 5-TMS-ethynyl-1,2,3-triazole derivative with the structure of formula III, which is characterized by including the following steps:

[0009]

[0010] In an organic solvent, bistrimethylsilylbutadiyne reacts with an azide derivative of formula IV by heating to obtain a 5-TMS-ethynyl-1,2,3-triazole derivative of formula III; wherein R2 is selected from C1-C8 alkyl, phenyl optionally substituted simultaneously by one or more phenyl, halophenyl, carbonyl (C=O), pyridyl, benzoyl, C1-C3 alkoxy, halogen; the molar amount of bistrimethylsilylbutadiyne is 1.0-2.0 times (preferably 1.0-1.2 times) that of the compound of formula IV. The heating reaction is preferably carried out by heating to 90 °C to the reflux temperature. The organic solvent is a conventional reaction solvent in the art, and those skilled in the art can reasonably select it according to the reaction characteristics and the properties of the reactants, such as benzene, alkylbenzene (such as toluene, xylene, etc.), halobenzene (such as chlorobenzene, etc.), preferably toluene, p-xylene, chlorobenzene, etc.

[0011] Compared with the prior art, the advantages of the present invention are as follows: (1) The present invention can directly use bistrimethylsilylbutadiyne as an inexpensive and easily available reagent to react with an azide compound to directly prepare a TMS-ethynyl-1,2,3-triazole structural compound; (2) The present invention can controllably install a TMS-ethynyl group at the C4 or C5 position of the 1,2,3-triazole ring; (3) Compared with the prior art, the present invention can directly realize the preparation of an ethynyl-1,2,3-triazole structural compound. In the 4-ethynyl-1,2,3-triazole structure, the reaction is very simple and convenient and has a cost advantage, greatly improving the synthesis efficiency of 4-ethynyl-1,2,3-triazole compounds; (4) Compared with the prior art, the present invention can directly realize the preparation of a 5-ethynyl-1,2,3-triazole structural compound for the first time.

[0012] It should be understood that within the scope of the present invention, the above technical features of the present invention and the technical features specifically described below (such as in the examples) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be elaborated one by one here. Description of the Drawings

[0013] Figure 1 is the 1 1H NMR spectrum of the product 4-(trimethylsilyl)ethynyl-1-phenyl-1,2,3-triazole in Example 1;

[0014] Figure 2 is the 13 13C NMR spectrum of the product 4-(trimethylsilyl)ethynyl-1-phenyl-1,2,3-triazole in Example 1;

[0015] Figure 3 is the 1 1H NMR spectrum of the product 4-(trimethylsilyl)ethynyl-1-(4-methoxyphenyl)-1,2,3-triazole in Example 2

[0016] Figure 4 is the product of Example 2, 4-(trimethylsilyl)ethynyl-1-(4-methoxyphenyl)-1,2,3-triazole 13 CNMR spectrum

[0017] Figure 5 is the 1 H NMR spectrum of the product of Example 3, 4-(trimethylsilyl)ethynyl-1-(3-bromophenyl)-1,2,3-triazole

[0018] Figure 6 is the 1 H NMR spectrum of the product of Example 3, 4-(trimethylsilyl)ethynyl-1-(3-bromophenyl)-1,2,3-triazole

[0019] Figure 7 is the 1 H NMR spectrum of the product of Example 4, 4-(trimethylsilyl)ethynyl-1-(2-chlorophenyl)-1,2,3-triazole;

[0020] Figure 8 is the 13 CNMR spectrum of the product of Example 4, 4-(trimethylsilyl)ethynyl-1-(2-chlorophenyl)-1,2,3-triazole;

[0021] Figure 9 is the 1 H NMR spectrum of the product of Example 5, 4-(trimethylsilyl)ethynyl-1-benzyl-1,2,3-triazole;

[0022] Figure 10 is the 13 C NMR spectrum of the product of Example 5, 4-(trimethylsilyl)ethynyl-1-benzyl-1,2,3-triazole;

[0023] Figure 11 is the 1 HNMR spectrum of the product of Example 6, 4-(trimethylsilyl)ethynyl-1-(4-methoxybenzyl)-1,2,3-triazole;

[0024] Figure 12 is the 13 CNMR spectrum of the product of Example 6, 4-(trimethylsilyl)ethynyl-1-(4-methoxybenzyl)-1,2,3-triazole;

[0025] Figure 13 is the 1 H NMR spectrum of the product of Example 7, 4-(trimethylsilyl)ethynyl-1-2,5,8,11-tetraoxatridecyl-1,2,3-triazole;

[0026] Figure 14 is the Figure 14 of the product 4-(trimethylsilyl)ethynyl-1-2,5,8,11-tetraoxatridecyl-1,2,3-triazole in Example 7 13 C NMR spectrum;

[0027] Figure 15 is the of the product 4-(trimethylsilyl)ethynyl-1-(2-oxo-2-phenylethyl)-1,2,3-triazole in Example 8 1 H NMR spectrum;

[0028] Figure 16 is the

[0027] of the product 4-(trimethylsilyl)ethynyl-1-(2-oxo-2-phenylethyl)-1,2,3-triazole in Example 8 13 C NMR spectrum;

[0029] Figure 17 is the Figure 15 of the product 4-(trimethylsilyl)ethynyl-1-[(pyridin-2-yl)methyl]-1,2,3-triazole in Example 9 1 H NMR spectrum;

[0030] Figure 18 is the of the product 4-(trimethylsilyl)ethynyl-1-[(pyridin-2-yl)methyl]-1,2,3-triazole in Example 9 13 C NMR spectrum;

[0031] Figure 19 is the

[0029] of the product 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-phenyl-1,2,3-triazole in Example 10 1 H NMR spectrum;

[0032] Figure 20 is the Figure 17 of the product 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-phenyl-1,2,3-triazole in Example 10 13 C NMR spectrum;

[0033] Figure 21 is the of the product 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-chlorophenyl)-1,2,3-triazole in Example 11 1 H NMR spectrum;

[0034] Figure 22 is the

[0030] of the product 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-chlorophenyl)-1,2,3-triazole in Example 11 13 C NMR spectrum;

[0035] Figure 23 is the Figure 18 of the product 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-bromophenyl)-1,2,3-triazole in Example 121 1H NMR spectrum;

[0036] Figure 24 of the product of Example 12, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-bromophenyl)-1,2,3-triazole 13 13C NMR spectrum;

[0037] Figure 25 of the product of Example 13, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-fluorophenyl)-1,2,3-triazole 1 1H NMR spectrum;

[0038] Figure 26 of the product of Example 13, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-fluorophenyl)-1,2,3-triazole 13 13C NMR spectrum;

[0039] Figure 27 of the product of Example 14, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-methoxyphenyl)-1,2,3-triazole 1 1H NMR spectrum;

[0040] Figure 28 of the product of Example 14, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(4-methoxyphenyl)-1,2,3-triazole 13 13C NMR spectrum;

[0041] Figure 29 of the product of Example 15, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-benzyl-1,2,3-triazole 1 1H NMR spectrum;

[0042] Figure 30 of the product of Example 15, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-benzyl-1,2,3-triazole 13 13C NMR spectrum;

[0043] Figure 31 of the product of Example 16, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(3-fluorobenzyl)-1,2,3-triazole 1 1H NMR spectrum;

[0044] Figure 32 of the product of Example 16, 4-trimethylsilyl-5-(trimethylsilyl)ethynyl-1-(3-fluorobenzyl)-1,2,3-triazole 13 13C NMR spectrum;

[0045] Figure 33 1H NMR spectrum of the product of Example 17, 4-trimethylsilyl-5-(trimethylsilylethynyl)-1-(2-bromobenzyl)-1,2,3-triazole 1 1H NMR spectrum

[0046] Figure 34 1H NMR spectrum of the product of Example 17, 4-trimethylsilyl-5-(trimethylsilylethynyl)-1-(2-bromobenzyl)-1,2,3-triazole 13 13C NMR spectrum

[0047] Figure 35 1H NMR spectrum of the product of Example 18, 4-trimethylsilyl-5-(trimethylsilylethynyl)-1-octyl-1,2,3-triazole 1 1H NMR spectrum

[0048] Figure 36 1H NMR spectrum of the product of Example 18, 4-trimethylsilyl-5-(trimethylsilylethynyl)-1-octyl-1,2,3-triazole 13 13C NMR spectrum

[0049] Figure 37 1H NMR spectrum of the product of Example 19, ethyl 4-(4-trimethylsilyl-5-(trimethylsilylethynyl)-1,2,3-triazol-1-yl)butyrate 1 1H NMR spectrum

[0050] Figure 38 1H NMR spectrum of the product of Example 19, ethyl 4-(4-trimethylsilyl-5-(trimethylsilylethynyl)-1,2,3-triazol-1-yl)butyrate 13 13C NMR spectrum

[0051] Figure 39 1H NMR spectrum of the product of Example 20, 4-trimethylsilyl-5-(trimethylsilylethynyl)-1-phenethyl-1,2,3-triazole 1 1H NMR spectrum

[0052] Figure 40 1H NMR spectrum of the product of Example 20, 4-trimethylsilyl-5-(trimethylsilylethynyl)-1-phenethyl-1,2,3-triazole 13 13C NMR spectrum Detailed implementation mode

[0053] For the convenience of further understanding of the present invention, the following examples provide more detailed descriptions thereof. However, these examples are only for better understanding of the invention and are not used to limit the scope or implementation principle of the present invention. The implementation modes of the present invention are not limited to the following content.

[0054]

[0055] General preparation method: In an organic solvent, bis(trimethylsilyl)butadiyne (BTMSBD), a compound of formula II (0.4 mmol), a copper salt, and an additive are added, and the mixture is stirred at room temperature until the reaction is complete as detected by TLC. The reaction solution is extracted with an organic solvent (preferably ethyl acetate, chloroform, or dichloromethane, etc.), washed, dried, concentrated, and then subjected to normal-phase silica gel column chromatography to obtain the compound of formula I (for the NMR spectrum, see Figure 1-18 ).

[0056]

[0057] Example 1: 1 H NMR (400 MHz, Chloroform-d) δ 8.07 (s, 1H), 7.71 (dd, J = 7.8, 2.0 Hz, 2H), 7.57–7.50 (m, 2H), 7.49–7.43 (m, 1H), 0.27 (s, 9H). 13 C NMR (100 MHz, Chloroform-d) δ 136.69, 131.89, 130.02, 129.26, 124.39, 120.74, 99.77, 93.28, -0.18.

[0058] Example 2: 1 H NMR (600 MHz, Chloroform-d) δ 7.98 (s, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 0.27 (s, 9H). 13 C NMR (150 MHz, Chloroform-d) δ 160.22, 131.66, 130.08, 124.57, 122.40, 115.03, 99.55, 93.41, 55.80, -0.17.

[0059] Example 3: 1 H NMR (400 MHz, Chloroform-d) δ 8.06 (s, 1H), 7.92 (t, J = 2.0 Hz, 1H), 7.66 (ddd, J = 8.1, 2.2, 1.0 Hz, 1H), 7.59 (ddd, J = 8.1, 1.9, 1.0 Hz, 1H), 7.41 (t, J = 8.1 Hz, 1H), 0.27 (s, 9H). 13 C NMR (100 MHz, Chloroform-d) δ 137.53, 132.27, 132.17, 131.33, 124.24, 123.83, 123.59, 119.10, 100.24, 92.88, -0.21.

[0060] Example 4 1 H NMR(400MHz,Chloroform-d)δ8.06(s,1H),7.59–7.51(m,2H),7.48–7.39(m,2H),0.24(s,9H). 13 C{ 1 H}NMR(101MHz,Chloroform-d)δ134.28,131.17,130.95,130.88,128.54,128.26,128.11,127.73,99.55,93.09,-0.27.

[0061] Example 5: 1 H NMR(400MHz,Chloroform-d)δ7.42(s,1H),7.25(dd,J=5.1,1.9Hz,3H),7.15–7.11(m,2H),5.39(s,2H),0.10(s,9H). 13 C NMR(100MHz,Chloroform-d)δ134.18,131.50,129.34,129.10,128.27,126.32,98.94,93.62,54.43,-0.21.

[0062] Example 6: 1 H NMR(600MHz,Chloroform-d)δ7.49(s,1H),7.22–7.19(m,2H),6.90–6.87(m,2H),5.44(s,2H),3.80(s,3H),0.22(s,9H). 13 C NMR(150MHz,Chloroform-d)δ160.22,131.39,129.91,126.14,126.09,114.70,98.85,93.68,55.50,54.01,-0.21.

[0063] Example 7: 1 H NMR(400MHz,Chloroform-d)δ7.89(s,1H),4.54–4.50(m,2H),3.85–3.80(m,2H),3.64–3.58(m,10H),3.53–3.50(m,2H),3.34(s,3H),0.23(s,9H). 1313C NMR (100 MHz, Chloroform-d) δ 130.89, 127.79, 98.41, 94.01, 71.98, 70.68, 70.66, 70.62, 70.59, 70.48, 69.31, 59.09, 50.51, -0.18.

[0064] Example 8: 1 1H NMR (400 MHz, Chloroform-d) δ 8.01–7.97 (m, 2H), 7.82 (s, 1H), 7.70–7.65 (m, 1H), 7.55 (t, J = 7.8 Hz, 2H), 5.84 (s, 2H), 0.26 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 189.79, 134.88, 133.91, 131.60, 129.37, 128.30, 99.09, 93.58, 55.56, -0.17.

[0065] Example 9: 1 1H NMR (400 MHz, Chloroform-d) δ 8.59 (d, J = 4.9 Hz, 1H), 7.84 (s, 1H), 7.69 (td, J = 7.7, 1.8 Hz, 1H), 7.29–7.25 (m, 1H), 7.20 (dd, J = 7.8, 1.1 Hz, 1H), 5.64 (s, 2H), 0.24 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 153.96, 149.94, 137.50, 131.46, 127.02, 123.67, 122.58, 98.93, 93.60, 55.76, -0.24.

[0066]

[0067] General preparation method: In an organic solvent, bis(trimethylsilyl)butadiyne ((BTMSBD), the compound of formula IV (0.3 mmol) were added, and the mixture was heated and stirred until the reaction was complete as detected by TLC. After concentration of the reaction solution, it was subjected to normal-phase silica gel column chromatography to obtain the compound of formula III (the NMR spectrum is shown in Figure 19-40 ).

[0068]

[0069]

[0070] Example 10: 11H NMR (400 MHz, Chloroform-d) δ 7.83–7.75 (m, 2H), 7.55–7.43 (m, 3H), 0.43 (s, 9H), 0.22 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 151.02, 136.60, 129.16, 129.13, 125.93, 123.74, 108.44, 91.74, -0.58, -1.41.

[0071] Example 11: 1 1H NMR (400 MHz, Chloroform-d) δ 7.78–7.73 (m, 2H), 7.50–7.46 (m, 2H), 0.42 (s, 9H), 0.23 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 151.35, 135.08, 135.03, 129.37, 125.81, 124.83, 109.04, 91.43, -0.58, -1.45.

[0072] Example 12: 1 1H NMR (400 MHz, Chloroform-d) δ 7.73–7.68 (m, 2H), 7.66–7.61 (m, 2H), 0.42 (s, 9H), 0.24 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 151.41, 135.59, 132.35, 125.76, 125.05, 123.03, 109.12, 91.43, -0.57, -1.45.

[0073] Example 13: 1 1H NMR (600 MHz, Chloroform-d) δ 7.78–7.73 (m, 2H), 7.22–7.17 (m, 2H), 0.42 (s, 9H), 0.22 (s, 9H). 13 13C NMR (150 MHz, Chloroform-d) δ 162.78 (d, J = 249.2 Hz), 151.08, 132.71, 126.04, 125.72 (d, J = 9.0 Hz), 116.15 (d, J = 23.0 Hz), 108.71, 91.47, -1.44., 108.71, 91.47, -0.58, -1.44. 19 19F NMR (564 MHz, Chloroform-d) δ -111.58.

[0074] Example 14: 1 H NMR(400MHz,Chloroform-d)δ7.69–7.64(m,2H),7.02–6.97(m,2H),3.87(s,3H),0.41(s,9H),0.21(s,9H). 13 C NMR(100MHz,Chloroform-d)δ160.07,150.72,129.75,125.97,125.16,114.19,108.10,91.80,55.71,-0.55,-1.41.

[0075] Example 15: 1 H NMR(400MHz,Chloroform-d)δ7.37–7.29(m,5H),5.55(s,2H),0.35(s,9H),0.25(s,9H). 13 C NMR(100MHz,Chloroform-d)δ150.29,135.02,128.83,128.53,128.47,126.43,108.34,91.13,52.37,-0.44,-1.39.

[0076] Example 16: 1 H NMR(400MHz,Chloroform-d)δ7.30(td,J=8.0,5.8Hz,1H),7.11(dd,J=7.7,0.7Hz,1H),7.06–6.97(m,2H),5.54(s,2H),0.35(s,9H),0.25(s,9H). 13 C NMR(100MHz,Chloroform-d)δ162.91(d,J=247.0Hz),150.46,137.27(d,J=7.4Hz),130.47(d,J=8.3Hz),126.47,124.08(d,J=3.0Hz),115.64(d,J=6.5Hz),115.43(d,J=5.3Hz),108.73,90.89,51.74(d,J=2.0Hz),-0.49,-1.41.

[0077] Example 17: 11H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J = 7.9 Hz, 1H), 7.26–7.21 (m, 1H), 7.16 (td, J = 7.8, 1.6 Hz, 1H), 6.87 (dd, J = 7.7, 1.7 Hz, 1H), 5.71 (s, 2H), 0.37 (s, 9H), 0.18 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 150.22, 134.61, 132.87, 129.68, 129.12, 127.96, 127.11, 122.74, 108.90, 90.38, 51.79, -0.52, -1.39.

[0078] Example 18: 1 1H NMR (400 MHz, Chloroform-d) δ 4.39–4.33 (m, 2H), 1.90 (t, J = 7.1 Hz, 2H), 1.33–1.24 (m, 10H), 0.90–0.82 (m, 3H), 0.37–0.33 (m, 9H), 0.28–0.24 (m, 9H). 13 13C NMR (101 MHz, Chloroform-d) δ 149.81, 126.38, 107.70, 91.20, 48.73, 31.84, 30.00, 29.18, 29.05, 26.60, 22.73, 14.20, -0.39, -1.39.

[0079] Example 19: 1 1H NMR (400 MHz, Chloroform-d) δ 4.44 (t, J = 6.7 Hz, 2H), 4.12 (q, J = 7.1 Hz, 2H), 2.38–2.31 (m, 2H), 2.24 (pd, J = 7.0, 1.4 Hz, 2H), 1.24 (t, J = 7.1 Hz, 3H), 0.36 (s, 9H), 0.27 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 172.50, 150.03, 126.54, 108.23, 90.80, 60.72, 47.71, 31.13, 25.08, 14.32, -0.40, -1.41.

[0080] Example 20: 11H NMR (400 MHz, Chloroform-d) δ 7.32–7.23 (m, 3H), 7.17–7.13 (m, 2H), 4.63–4.55 (m, 2H), 3.25–3.16 (m, 2H), 0.36 (s, 9H), 0.28 (s, 9H). 13 13C NMR (100 MHz, Chloroform-d) δ 149.90, 137.32, 128.89, 128.84, 127.07, 126.64, 107.85, 90.84, 49.94, 36.71, -0.36, -1.43。

Claims

1. A method for synthesizing a 4-TMS-ethynyl-1,2,3-triazole derivative of formula I, characterized in that It includes the following steps: In an organic solvent, bis(trimethylsilyl)butadiyne reacts with an azide derivative of formula II under the action of a copper salt and an additive to obtain a 4-TMS-ethynyl-1,2,3-triazole derivative of formula I; wherein R1 is selected from C1-C3 alkyl, phenyl optionally substituted simultaneously by one or more phenyl, halophenyl, pyridyl, benzoyl, C1-C3 alkoxy, halogen; the copper salt is selected from monovalent copper salts or complexes of monovalent copper salts, and the additive is selected from nitrogen-containing ligands or phosphorus-containing ligands.

2. The synthesis method according to claim 1, characterized in that The monovalent copper salt is selected from one or more mixtures of cuprous chloride, cuprous bromide, and cuprous iodide.

3. The synthesis method according to any one of claims 1-2, characterized in that The additive is selected from one or more mixtures of triethylamine, pyridine, tetramethylethylenediamine, diisopropylethylamine, triphenylphosphine, 2,2'-bipyridine, N,N-dimethylaminopyridine, 1,10-phenanthroline.

4. The synthesis method according to any one of claims 1 to 3, characterized in that The molar amount of bis(trimethylsilyl)butadiyne is 1.0 - 2.0 times (preferably 1.2 - 1.5 times) that of the compound of formula II.

5. The synthesis method according to any one of claims 1-4, characterized in that The molar amount of the copper salt is 0.05 - 0.1 times that of the compound of formula II.

6. The synthesis method according to any one of claims 1-5, characterized in that The molar amount of the additive is 0.5 - 2.0 times (preferably 1.0 - 1.5 times) that of the compound of formula II.

7. A method for synthesizing a 5-TMS-ethynyl-1,2,3-triazole derivative of the formula III structure, characterized in that It includes the following steps: In an organic solvent, bis(trimethylsilyl)butadiyne reacts with an azide derivative of formula IV by heating to obtain a 5-TMS-ethynyl-1,2,3-triazole derivative of formula III; wherein R2 is selected from C1-C8 alkyl, phenyl optionally substituted simultaneously by one or more phenyl, halophenyl, carbonyl (C=O), pyridyl, benzoyl, C1-C3 alkoxy, halogen.

8. The synthesis method according to claim 7, characterized in that The molar amount of bis(trimethylsilyl)butadiyne is 1.0 - 2.0 times (preferably 1.0 - 1.2 times) that of the compound of formula IV.

9. The synthesis method according to any one of claims 7-8, characterized in that The heating reaction is selected from reacting by heating to 90°C to the reflux temperature.

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