A method for synthesizing a diiodo 1,2,3-triazole compound

Abstract

The application belongs to the field of medicine synthesis and organic chemical industry, and relates to a synthesis method of diiodo 1,2,3-triazole compound, wherein azide compound, additive and solvent are added into a reaction container, air in the reaction container is replaced by nitrogen, acetylene gas is introduced into the reaction system, and the reaction is stirred at 0-50 DEG C, after the reaction is completed, the reaction product is separated, and the diiodo 1,2,3-triazole compound is obtained. The application is based on the cycloaddition reaction of acetylene and azide compound, copper salt, alkali and iodine salt are used as additives, the expected product is obtained through the cycloaddition reaction of the organic molecule containing azide functional group, the synthesis system of diiodo 1,2,3-triazole compound is established, the synthesis efficiency of 1,2,3-triazole compound is improved, the reaction system is mild, the reaction conversion rate is high, impurities are few, the product is easy to purify, and the operation is strong.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of drug synthesis and organic chemical industry, and relates to a synthesis method of a compound, in particular to a synthesis method of a di-iodo 1,2,3-triazole compound. BACKGROUND

[0002] 1,2,3-triazole is an important five-ring heterocyclic aromatic ring, which has been widely used in the fields of medicine, pesticide and material. As an important intermediate of 1,2,3-triazole, iodo-1,2,3-triazole is a special triazole structure compound, which can be used to construct polysubstituted 1,2,3-triazole and its derivatives. For example, Wu and Chen et al. converted 5-iodo-1,4-disubstituted-1,2,3-triazole into 1,4,5-trisubstituted-1,2,3-triazole through Suzuki coupling reaction, Heck coupling reaction and Sonogashira coupling reaction. In 2020, a strategy for synthesizing benzoxazoles by using iodo-triazole as a stable diazo precursor was reported.

[0003] At present, there are many methods for preparing iodo-1,2,3-triazole. These reactions include: copper-catalyzed cycloaddition reaction of iodo-alkyne and azide compound to synthesize iodo-1,2,3-triazole; iodination reaction of triazole-metal intermediate and iodo reagent to prepare iodo-1,2,3-triazole through cyclization reaction of terminal alkyne and azide compound, etc. The triazole metal intermediates used include triazolyl magnesium halide and triazole-copper intermediate, and the iodo reagents or components used include ICl, I2, CuI and NBS, Cu(ClO4)2 / NaI. 4-iodo-1,2,3-triazole or 5-iodo-1,2,3-triazole can be synthesized through these reactions. Among them, the azide-alkyne cycloaddition tandem reaction is the most commonly used strategy for synthesizing iodo-triazole. 5-iodo-triazole can be prepared by synthesizing iodo-triazole through azide-alkyne cycloaddition reaction. In 2005, the synthesis of 5-iodo-triazole prepared in situ by using electrophilic reagents such as iodine chloride was first reported in the related literature. In the reaction, a stoichiometric amount of CuI and ICl were used as iodo reagents. This method has wide applicability and good compatibility for various alkyne compounds, such as alkyne compounds containing aromatic structure, alkyl, ester group and amide. + and I + + + ​​The carbon anion intermediate generated by catalytic azide alkyne cycloaddition reaction is captured, thereby achieving efficient synthesis of iodotriazole. Subsequently, multiple studies continue to develop different reaction systems to synthesize iodotriazole, such as Cu(ClO4)2 / NaI, CuCl2 / NaI, etc. Through the cycloaddition reaction of iodinated alkyne and azide compound, it is also a common method for preparing iodotriazole. Although the above studies can synthesize 4-iodo-1,2,3-triazole or 5-iodo-1,2,3-triazole, these synthesis reactions can only synthesize mono-iodinated 1,2,3-triazole compounds. Through retrieval, there is no related report on the synthesis method of di-iodinated 1,2,3-triazole. SUMMARY

[0004] The purpose of the present application is to provide a synthesis method of di-iodinated 1,2,3-triazole compounds, based on the cycloaddition reaction of ethyne and azide compound, using copper salt, base and iodine salt as additives, to establish a synthesis system of di-iodinated 1,2,3-triazole compounds.

[0005] The technical scheme adopted by the present application is as follows:

[0006] A synthesis method of di-iodinated 1,2,3-triazole compounds, comprising the following steps:

[0007]

[0008] In a solvent, azide compound of formula I reacts with ethyne in the presence of additives to generate compound of formula II, which is di-iodinated 1,2,3-triazole compound with two iodine atoms, wherein R is optionally aryl or alkyl; the additive is a mixture of copper salt, base and iodine salt.

[0009] Further, the synthesis method of di-iodinated 1,2,3-triazole compounds has the following specific process: azide compound, additive and solvent are added to a reaction container, the air in the reaction container is replaced with nitrogen, then ethyne gas is introduced, and the reaction is stirred at 0-50℃; after the reaction is completed, the reaction product is separated to obtain di-iodinated 1,2,3-triazole compound; the additive is a mixture of copper salt, base and iodine salt. The reaction can be carried out under pressure or under normal pressure. Ethyne can be industrial ethyne gas or prepared by in-situ reaction of calcium carbide with water.

[0010] Further, the solvent is one of dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, hexamethylphosphoramide, dioxane, methyl tert-butyl ether, 2-methylfuran, or a mixture of any two or more thereof, wherein N,N-dimethylformamide is preferred.

[0011] Further, the molar ratio of copper salt to azide compound is 1:1-1:4.

[0012] Further, the copper salt is a divalent copper salt (such as CuBr2, CuCl2, Cu(NO3)2, Cu(ClO4)2, etc.) or a hydrate of the divalent copper salt (such as CuCl2.2H2O, Cu(NO3)2.3H2O, Cu(ClO4)2.6H2O, etc.), wherein CuCl2.2H2O is preferred.

[0013] Further, the base is one of triethylamine, pyridine, N,N-diisopropylethylamine, N,N-dimethylpyridine, 1,10-phenanthroline and its substitutes, 2,2'-bipyridine, or sodium carbonate, wherein pyridine is preferred.

[0014] The present application is based on the cycloaddition reaction of ethyne and azido compound, with copper salt, base and iodine salt as additives, to obtain the expected product through the cycloaddition reaction of organic molecules containing azido functional groups, to establish the synthesis system of diiodo 1,2,3-triazole compound, to improve the synthesis efficiency of 1,2,3-triazole compound, the reaction system is mild, the reaction conversion rate is high, the impurities are few, it is easy to purify, and the operability is strong. DETAILED DESCRIPTION

[0015] The specific embodiments of the present application will be further described in detail below with reference to the examples. The following examples are used to illustrate the present application, but not to limit the scope of the present application. In the following examples, the experimental methods are conventional methods, unless otherwise specified. In the following examples, the materials, reagents, etc. are commercially available, unless otherwise specified, wherein analytical reagent is preferred.

[0016] Example 1, preparation of 1-phenyl-4,5-diiodo-1,2,3-triazole

[0017] The structural formula is as follows:

[0018]

[0019] Scheme 1: In a dry 10 mL flask, azidobenzene (1.0 mmol, 1.0 equiv.), CuCl2.2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added in turn. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at room temperature for 24 h. After the reaction was completed, the reaction liquid was extracted, washed, dried and solvent was removed, and column chromatography was used to separate to obtain the corresponding product 1-phenyl-4,5-diiodo-1,2,3-triazole, with a yield of 64%.

[0020] Scheme 2: In a dry 10 mL flask, add azidobenzene (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), DMAP (2.0 mmol, 2.0 equiv.), dimethyl sulfoxide (2.0 mL) in sequence. After the air in the flask is replaced by nitrogen, acetylene gas is introduced, and the reaction is stirred at 10 °C for 24 h. After the reaction is completed, the reaction solution is subjected to the above operation to obtain the corresponding product 1-phenyl-4,5-diiodo-1,2,3-triazole, with a yield of 45%.

[0021] Yellow solid; mp: 152.9-155.7 °C; 71% yield; 1 H NMR (400 MHz, CDC13) δ 7.59-7.55 (m, 3H), 7.50 (dd, J = 6.8, 3.0 Hz, 2H). 13 C NMR (100 MHz, CDC13) δ 137.22, 130.63, 129.57, 129.47, 126.12, 125.94, 102.57, 91.51.

[0022] Example 2, Preparation of 1-(p-tolyl)-4,5-diiodo-1,2,3-triazole

[0023] The structural formula is as follows:

[0024]

[0025] Scheme 1: In a dry 10 mL flask, add p-tolyl azide (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (4.0 mmol, 4.0 equiv.), NaI (8.0 mmol, 4.0 equiv.), N,N-dimethylpyridine (2.0 mmol, 2.0 equiv.), N-methylpyrrolidone (4.0 mL) in sequence. After the air in the flask is replaced by nitrogen, acetylene gas is introduced, and the reaction is stirred at room temperature for 24 h. After the reaction is completed, the reaction solution is subjected to extraction, washing, drying, and solvent stripping, and then column chromatography to obtain the corresponding product 1-(p-tolyl)-4,5-diiodo-1,2,3-triazole, with a yield of 70%.

[0026] Scheme 2: The copper salt required in the reaction is replaced by CuBr2 (1.0 mmol, 1.0 equiv.), and the base used is 2,6-Lutidine (1.0 mmol, 1.0 equiv.). After the reaction is completed, the reaction solution is subjected to the above operation to obtain the corresponding target product, with a yield of 48%.

[0027] White soild;mp:144.9-147.5℃;37%yield;1H NMR(400MHz,Chloroform-d)δ7.40–7.32(m,4H),2.46(s,3H).13C NMR(100MHz,Chloroform-d)δ140.98,134.77,130.10,125.70,102.32,91.69,21.47.

[0028] Example 3: Preparation of 1-(p-ethylphenyl)-4,5-diiodo-1,2,3-triazole

[0029] The structure is as follows:

[0030]

[0031] In a dry 10 mL flask, p-ethylphenyl azide (1.0 mmol, 1.0 equiv.), Cu(ClO4)2·6H2O (2.0 mmol, 2.0 equiv.), KI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), and N,N-dimethylformamide (2.0 mL) were added sequentially. The air in the flask was replaced with nitrogen, and then acetylene gas was introduced. The reaction mixture was stirred at 30 °C for 24 h. After the reaction was complete, the reaction solution was extracted, washed, dried, and solvent removed. The solution was then separated by column chromatography to obtain the product 1-(p-ethylphenyl)-4,5-diiodo-1,2,3-triazole, with a yield of 69%.

[0032] Pale yellow solid; mp:179.5-181.4℃; 67% yield; 1 H NMR (400MHz, CDCl3) δ7.44–7.31(m,4H),2.74(q,J=7.6Hz,2H),1.28(t,J=7.6Hz,3H). 13 C NMR (100MHz, CDCl3) δ 147.04, 134.79, 128.86, 125.68, 102.32, 91.81, 28.67, 15.40. Example 4: Preparation of 1-(p-methoxyphenyl)-4,5-diiodo-1,2,3-triazole

[0033] The structure is as follows:

[0034]

[0035] In a dry 10 mL flask, 4-methoxyphenyl azide (1.0 mmol, 1.0 equiv.), Cu(NO3)2-3H2O (2.0 mmol, 2.0 equiv.), tetrabutylammonium iodide (4.0 mmol, 4.0 equiv.), N,N-diethylisopropylamine (2.0 mmol, 2.0 equiv.), N-methylpyrrolidone (2.0 mL) were added successively. After the air in the flask was replaced by nitrogen, acetylene gas was bubbled into the flask, and the reaction was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried, and the solvent was stripped off, and the product 1-(p-methoxyphenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 62%.

[0036] White solid; mp: 142.1-145.2 °C; 60% yield; 1 H NMR (400 MHz, CDC13) δ 7.40 (d, J = 8.9 Hz, 1H), 7.04 (d, J = 8.9 Hz, 1H), 3.89 (s, 2H). 13 C NMR (100 MHz, CDC13) δ 161.09, 130.13, 127.34, 114.60, 102.07, 92.19, 55.81.

[0037] Example Five, Preparation of 1-(p-bromophenyl)-4,5-diiodo-1,2,3-triazole

[0038] The structural formula is as follows:

[0039]

[0040] In a dry 10 mL flask, 4-methoxyphenyl azide (1.0 mmol, 1.0 equiv.), Cu(NO3)2-3H2O (2.0 mmol, 2.0 equiv.), tetrabutylammonium iodide (4.0 mmol, 4.0 equiv.), N,N-diethylisopropylamine (2.0 mmol, 2.0 equiv.), N-methylpyrrolidone (2.0 mL) were added successively. After the air in the flask was replaced by nitrogen, acetylene gas was bubbled into the flask, and the reaction was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried, and the solvent was stripped off, and the product 1-(p-methoxyphenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 62%.

[0041] Pale yellow soild; mp: 177.3-180.8 °C; 60% yield; 1H NMR (400 MHz, CDC13) δ 8.04 (s, 0.06H), 7.71 (d, J = 8.7 Hz, 2H), 7.46 - 7.37 (m, 2H). 13 C NMR (100 MHz, CDC13) δ 136.10, 132.87, 127.40, 124.91, 102.88, 91.37.

[0042] Example Six, Preparation of 1-(p-Chlorophenyl)-4,5-diiodo-1,2,3-triazole

[0043] The structure is as follows:

[0044]

[0045] In a dry 10 mL flask, 4-chlorophenyl azide (1.0 mmol, 1.0 equiv.), CuBr2(2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (4.0 mmol, 2.0 equiv.), N, N-dimethylacetamide (2.0 mL) were added in turn. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at 40°C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried and solvent stripped, and the corresponding product 1-(p-chlorophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 64%.

[0046] Pale yellow solid; mp: 177.3-180.5°C; 56% yield; 1 H NMR (400 MHz, CDC13) δ 7.57 - 7.52 (m, 1H), 7.47 (d, J = 8.8 Hz, 1H). 13 C NMR (100 MHz, CDC13) δ 136.78, 135.55, 129.85, 127.17, 102.82, 91.56.

[0047] Example Seven, Preparation of 1-(p-Trifluoromethylphenyl)-4,5-diiodo-1,2,3-triazole

[0048] The structure is as follows:

[0049]

[0050] Into a dry 10 mL flask, 4-azidobenzonitrile (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added successively. After the air in the flask was replaced by nitrogen, acetylene gas was bubbled into the flask, and the reaction was stirred at 35 °C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried and the solvent was distilled off, and the product 1-(p-cyanophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 68%.

[0051] Pale yellow soild; mp: 180.3-185.9 °C; 68% yield; 1 H NMR (400 MHz, CDC13) δ 7.85 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H). 13 C NMR (100 MHz, CDC13) δ 139.72, 132.57 (q, J = 33.2 Hz), 126.86 (q, J = 3.8 Hz), 126.28, 123.44 (q, J = 272.8 Hz), 103.33, 91.23.

[0052] Example Eight, Preparation of 1-(p-cyanophenyl)-4,5-diiodo-1,2,3-triazole

[0053] The structural formula is as follows:

[0054]

[0055] Into a dry 10 mL flask, 4-azidobenzonitrile (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added successively. After the air in the flask was replaced by nitrogen, acetylene gas was bubbled into the flask, and the reaction was stirred at 35 °C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried and the solvent was distilled off, and the product 1-(p-cyanophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 68%.

[0056] Pale yellow soild; mp: 180.3-185.9 °C; 68% yield; 1H NMR (400 MHz, CDC13) δ 7.90 (d, J = 8.6 Hz, 1H), 7.74 (d, J = 8.7 Hz, 1H). 13 C NMR (100 MHz, CDC13) δ 140.22, 134.21, 133.61, 126.50, 120.78, 117.50, 114.63.

[0057] Example Nine, Preparation of 1-(m-Tolyl)-4,5-diiodo-1,2,3-triazole

[0058] The structural formula is as follows:

[0059]

[0060] In a dry 10 mL flask, m-methylanilino (1.0 mmol, 1.0 equiv.), CuCl2·2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added in turn. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at 45°C for 24 h. After the reaction was completed, the reaction liquid was extracted, washed, dried and solvent stripped, and column chromatography was used to separate the corresponding product 1-(m-tolyl)-4,5-diiodo-1,2,3-triazole, with a yield of 68%.

[0061] White solid; mp: 112.7-123.6°C; 51% yield; 1 H NMR (400 MHz, CDC13) δ 7.44 (t, J = 7.7 Hz, 1H), 7.36 (d, J = 7.7 Hz, 1H), 7.32-7.25 (m, 2H), 2.45 (s, 3H). 13 CNMR (100 MHz, Chloroform-d) δ 139.91, 137.08, 131.36, 129.26, 126.42, 122.94, 102.43, 91.57, 21.44.

[0062] Example Ten, Preparation of 1-(m-Bromophenyl)-4,5-diiodo-1,2,3-triazole

[0063] The structural formula is as follows:

[0064]

[0065] In a dry 10 mL flask, add m-bromophenyl azide (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) in sequence. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried, and the solvent was removed. The product 1-(m-bromophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography with a yield of 64%.

[0066] White solid; mp: 164.0-169.6 °C; 53% yield; 1 H NMR (400 MHz, CDC13) δ 8.07 (s, 0.03H), 7.91 (s, 0.03H), 7.74-7.67 (m, 2H), 7.53-7.41 (m, 2H). 13 C NMR (100 MHz, CDC13) δ 138.04, 133.78, 130.81, 129.06, 124.58, 122.94, 102.93, 91.39.

[0067] The structural formula is as follows:

[0068]

[0069] In a dry 10 mL flask, add m-bromophenyl azide (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) in sequence. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at room temperature for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried, and the solvent was removed. The product 1-(m-bromophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography with a yield of 64%.

[0070] Yellow solid; mp: 156.4-159.1 °C; 58% yield; 1H NMR (400 MHz, CDC13) δ 8.07 (s, 0.03H), 7.86 (s, 0.09H), 7.58 - 7.53 (m, 2H), 7.51 (d, J = 8.6 Hz, 1H), 7.44 (dt, J = 7.6, 1.8 Hz, 1H). 13 C NMR (100 MHz, CDC13) δ 137.97, 135.33, 130.87, 130.60, 126.25, 124.13, 102.93, 91.36.

[0071] Example Twelve, Preparation of 1-(m-trifluoromethylphenyl)-4,5-diiodo-1,2,3-triazole

[0072] The structural formula is as follows:

[0073]

[0074] In a dry 10 mL flask, m-trifluoromethylphenyl azide (1.0 mmol, 1.0 equiv.), CuCl2-2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added in sequence. After the air in the flask was replaced by nitrogen, acetylene gas was introduced, and the reaction was stirred at 35 °C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried, and solvent-stripped, and the corresponding product 1-(m-trifluoromethylphenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography with a yield of 58%.

[0075] White solid; mp: 143.6-148.1 °C; 61% yield; 1 H NMR (400 MHz, CDC13) δ 7.84 (d, J = 2.4 Hz, 2H), 7.79 - 7.69 (m, 2H). 13 C NMR (100 MHz, CDC13) δ 137.45, 132.27 (q, J = 33.6 Hz), 130.40, 129.13, 127.36 (q, J = 3.5 Hz), 123.21 (q, J = 273.0 Hz), 123.05 (q, J = 3.9 Hz), 103.17, 91.47.

[0076] Example Thirteen, Preparation of 1-(o-tolyl)-4,5-diiodo-1,2,3-triazole

[0077] The structural formula is as follows:

[0078]

[0079] Into a dry 10 mL flask, 2-iodophenyl azide (1.0 mmol, 1.0 equiv.), Cu(OAc)2-2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added successively. After the air in the flask was replaced by nitrogen, acetylene gas was bubbled into the flask, and the reaction was stirred at 40 °C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried and the solvent was stripped off, and the product 1-(2-iodophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 64%.

[0080] White solid; mp: 154.1-159.5 °C; 51% yield; 1 H NMR (400 MHz, CDC13) δ 7.86 (s, 0.03H), 7.47 (td, J = 7.5, 1.3 Hz, 1H), 7.42 - 7.32 (m, 2H), 7.19 (dd, J = 7.9, 1.3 Hz, 1H), 2.03 (s, 3H). 13 C NMR (100 MHz, CDC13) δ 136.37, 135.56, 131.37, 131.20, 127.58, 127.01, 101.23, 93.34, 17.52.

[0081] Example Fourteen, Preparation of 1-(2-methoxyphenyl)-4,5-diiodo-1,2,3-triazole

[0082] The structural formula is as follows:

[0083]

[0084] Into a dry 10 mL flask, 2-iodophenyl azide (1.0 mmol, 1.0 equiv.), Cu(OAc)2-2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added successively. After the air in the flask was replaced by nitrogen, acetylene gas was bubbled into the flask, and the reaction was stirred at 40 °C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried and the solvent was stripped off, and the product 1-(2-iodophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 64%.

[0085] White solid; mp: 158.3-160.6 °C; 46% yield; 1 H NMR (400 MHz, CDC13) δ 7.54 (ddd, J = 8.2, 7.6, 1.7 Hz, 1H), 7.29 (dd, J = 7.7, 1.7 Hz, 1H), 7.14 - 7.05 (m, 2H), 3.81 (s, 3H). 13 CNMR (100 MHz, CDC13) δ 154.14, 132.60, 128.59, 125.90, 120.87, 112.34, 101.07, 94.15, 55.86.

[0086] Example Fifteen, Preparation of 1-(o-Bromophenyl)-4,5-diiodo-1,2,3-triazole

[0087] The structural formula is as follows:

[0088]

[0089] In a dry 10 mL flask, o-bromophenyl azide (1.0 mmol, 1.0 equiv.), CuCl2·2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added in turn. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at 40 °C for 24 h. After the reaction was completed, the reaction liquid was extracted, washed, dried and solvent stripped, and the corresponding product 1-(o-bromophenyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 56%.

[0090] White solid; mp: 158.6-160.9 °C; 56% yield; 1 H NMR (400 MHz, CDC13) δ 7.80 (dd, J = 7.9, 1.5 Hz, 1H), 7.57 - 7.45 (m, 2H), 7.37 (dd, J = 7.6, 1.8 Hz, 1H). 13 CNMR (100 MHz, CDC13) δ 136.59, 133.96, 132.69, 129.56, 128.64, 121.97, 93.59, 89.04.

[0091] Example Sixteen, Preparation of 1-(o-Chlorophenyl)-4,5-diiodo-1,2,3-triazole

[0092] The structural formula is as follows:

[0093]

[0094] Into a dry 10 mL flask, add chlorophenyl azide (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) in sequence. After the air in the flask is replaced by nitrogen, acetylene gas is introduced, and the reaction is stirred at room temperature for 24 h. After the reaction is completed, the reaction solution is extracted, washed, dried, and solvent-stripped, and the product 1-(o-chlorophenyl)-4,5-diiodo-1,2,3-triazole is obtained by column chromatography, with a yield of 64%.

[0095] White solid; mp: 179.1-183.2 °C; 57% yield; 1 H NMR (400 MHz, CDC13) δ 8.07 (s, 0.01H), 7.89 (s, 0.09H), 7.63 (dd, J = 8.0, 1.5 Hz, 1H), 7.56 (td, J = 7.7, 1.7 Hz, 1H), 7.49 (td, J = 7.7, 1.6 Hz, 1H), 7.39 (dd, J = 7.8, 1.7 Hz, 1H). 13 C NMR (100 MHz, CDC13) δ 134.93, 132.54, 132.24, 130.81, 129.46, 127.98, 101.38, 93.66.

[0096] The structural formula is as follows:

[0097]

[0098] Into a dry 10 mL flask, add benzyl azide (1.0 mmol, 1.0 equiv.), CuCl2 2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) in sequence. After the air in the flask is replaced by nitrogen, acetylene gas is introduced, and the reaction is stirred at room temperature for 24 h. After the reaction is completed, the reaction solution is extracted, washed, dried, and solvent-stripped, and the product 1-benzyl-4,5-diiodo-1,2,3-triazole is obtained by column chromatography, with a yield of 56%.

[0099] White solid; mp: 96.9-98.2 °C; 56% yield;1 H NMR (400 MHz, CDC13) δ 7.39 - 7.29 (m, 2H), 7.30 - 7.21 (m, 1H), 5.64 (s, 1H). 13 C NMR (100 MHz, CDC13) δ 133.71, 129.00, 128.77, 127.92, 101.80, 90.68, 55.59.

[0100] Example Eighteen, Preparation of 1-n-octyl-4,5-diiodo-1,2,3-triazole

[0101] The structural formula is as follows:

[0102]

[0103] In a dry 10 mL flask, n-nonyl azide (1.0 mmol, 1.0 equiv.), CuCl2·2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) were added in turn. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at 20°C for 24 h. After the reaction was completed, the reaction liquid was extracted, washed, dried and solvent-stripped, and the corresponding product 1-n-octyl-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 53%.

[0104] White solid; mp: 46.0-46.7°C; 53% yield; 1 H NMR (400 MHz, CDC13) δ 7.39 - 7.29 (m, 2H), 7.30 - 7.21 (m, 1H), 5.64 (s, 1H).

[0105] Example Nineteen, Preparation of 1-(a-naphthyl)-4,5-diiodo-1,2,3-triazole

[0106] The structural formula is as follows:

[0107]

[0108] In a dry 10 mL flask, add α-naphthylbenzene (1.0 mmol, 1.0 equiv.), CuCl2·2H2O (2.0 mmol, 2.0 equiv.), NaI (4.0 mmol, 4.0 equiv.), pyridine (2.0 mmol, 2.0 equiv.), N,N-dimethylformamide (2.0 mL) in sequence. After replacing the air in the flask with nitrogen, acetylene gas was introduced, and the reaction was stirred at 45°C for 24 h. After the reaction was completed, the reaction solution was extracted, washed, dried, and solvent-stripped, and the product 1-(α-naphthyl)-4,5-diiodo-1,2,3-triazole was obtained by column chromatography, with a yield of 50%.

[0109] Yellow solid; mp: 171.3-175.4°C; 44% yield; 1 H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.3 Hz, 1H), 7.98 (d, J = 7.7 Hz, 1H), 7.66-7.55 (m, 2H), 7.57-7.44 (m, 2H), 7.15 (dd, J = 8.4, 1.0 Hz, 1H). 13 C NMR (100 MHz, CDCl3) δ 134.14, 133.58, 131.66, 129.28, 128.49, 128.30, 127.42, 125.87, 124.98, 122.25, 101.49, 94.41.

[0110] The above only describes the preferred embodiments of the present application, and it should be noted that for those skilled in the art, without departing from the technical principles of the present application, a number of improvements and refinements can be made, and these improvements and refinements should also be considered within the scope of protection of the present application.

Claims

1. A method for synthesizing diiodo-1,2,3-triazole compounds, characterized in that, Includes the following steps: In a solvent, the azide compound of formula I reacts with acetylene in the presence of an additive to generate a compound of formula II, wherein the compound of formula II is a diiodo-1,2,3-triazole compound having two iodine atoms, wherein R is optionally aryl or alkyl; the additive is a mixture of copper salt, base and iodide salt; The specific process of the synthesis method is as follows: the azide compound, additives and solvent are added to the reaction vessel, the air in the reaction vessel is replaced with nitrogen, and then acetylene gas is introduced. The reaction is stirred at 0-50°C. After the reaction is completed, the reaction product is separated to obtain the diiodo-1,2,3-triazole compound. The additive is a mixture of copper salt, base and iodide salt. The copper salt is a divalent copper salt or a hydrate of divalent copper salt. The base is one of triethylamine, pyridine, N,N-diisopropylethylamine, N,N-dimethylpyridine, 1,10-phenanthroline and its substituted products, 2,2'-bipyridine or sodium carbonate.

2. The synthesis method according to claim 1, characterized in that: The solvent is one of dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, tetrahydrofuran, hexamethylphosphoryltetramine, dioxane, methyl tert-butyl ether, 2-methylfuran, or any mixture of two or more of these.

3. The synthesis method according to claim 1, characterized in that: The molar ratio of the copper salt to the azide compound is 1:1 to 1:4.

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