CN110590685A - Preparation method and application of a novel 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole - Google Patents

Abstract

The invention belongs to the technical field of organic synthesis, and provides a preparation method and application of a novel 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole. In the present invention, the preparation method of 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole and 5-thio-1,4,5-trisubstituted 1,2, The preparation method of 3-triazole has mild reaction conditions, and the product yield is not less than 62%. The preparation method has mild reaction conditions, greenness and high reaction efficiency, and is more suitable for large-scale production requirements, and the prepared 5-thio-1,4,5-trisubstituted 1,2,3-triazole compounds have potential physiological activity.

Description

Preparation of a novel 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole Preparation method and application

technical field

The invention belongs to the technical field of organic synthesis, and relates to a preparation method of a novel 5-thio-1,4,5-trisubstituted 1,2,3-triazole, comprising 5-thiocyanate-substituted 1,4-triazole , The preparation method of 5-trisubstituted 1,2,3-triazole and the preparation method of 5-thio-1,4,5-trisubstituted 1,2,3-triazole.

Background technique

The azide-alkyne cycloaddition reaction is one of the most important methods for the preparation of 1,2,3-triazoles. In recent years, a series of literatures or patents have reported the preparation methods of 1,2,3-triazole compounds. However, the method of producing 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole in a cycloaddition reaction involving an alkyne in an azide-thiocyanate group, Not yet reported in the literature. How to realize the cycloaddition reaction involving alkynes in the azide-thiocyanate group and improve the regioselectivity of the reaction is the focus of our attention. 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazoles can theoretically be further converted to 5-thio-1,4,5 by reacting with Grignard or lithium reagents - Trisubstituted 1,2,3-triazoles. But so far there are no relevant reports. Although some azido-thioendyne cycloadditions have been reported to prepare 5-thio-1,4,5-trisubstituted 1,2,3-triazoles (Angew.Chem.Int .Ed.2017,56,10766 and Angew.Chem.Int.Ed.2014,53,1877), but for the preparation of 5-thio- The technology of 1,4,5-trisubstituted 1,2,3-triazole still needs to be further developed. 5-thio-1,4,5-trisubstituted 1,2,3-triazoles are important compounds with potential biological activity, so it is of great significance to study their preparation methods.

The invention adopts various thiocyanate-based internal alkynes and organic azide compounds as raw materials, uses 2.5mol% [Cp*Ru(COD)Cl] as a catalyst, and reacts at room temperature for 12-24 hours. 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole compounds were obtained in a yield of 66% to 85%. Then, various thiocyanate-based alkynes, organic azides and Grignard reagents or lithium reagents were used as raw materials, and 2.5mol% [Cp*Ru(COD)Cl] was used as a catalyst. method" reaction, in 24-36 hours, 5-thio-1,4,5-trisubstituted 1,2,3-triazole compounds were finally obtained with a yield of 62% to 79%.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to provide a preparation method for synthesizing 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole and 5-thio-1,4,5- Preparation method of trisubstituted 1,2,3-triazoles.

Technical scheme of the present invention:

A preparation method of a novel 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole, the steps are as follows:

Catalysis of thiocyanate-based internal alkynes under the action of pentamethylcyclopentadienyl 1,5-cyclooctadienyl ruthenium chloride ([Cp*Ru(COD)Cl]) catalyst in organic solvent 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazoles are prepared by the reaction of these compounds with organic azides, and the reaction formula is as follows:

wherein, R ¹ and R ² are alkyl or aryl groups, and R ¹ and R ² are the same or different;

I is a thiocyanate group internal alkyne compound;

The molar ratio of the alkyne compound in the thiocyanate group to the organic azide compound is 1:1.5-1:3, and the concentration of the alkyne compound in the thiocyanate group in the system is 0.01-0.1mmol/ ml;

The dosage of the [Cp*Ru(COD)Cl] is 0.5-50 mol% of the alkyne compound in the thiocyanate group;

The reaction temperature is room temperature to 80°C, and the reaction time is 12h to 24h, and the 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole is prepared in a yield of not less than 66%. ;

Described organic solvent is benzene, toluene, ether, methyl tertiary butyl ether, dichloromethane, tetrahydrofuran, trifluorotoluene, cyclohexane, one or more mixing of petroleum ether, preferably solvent is tetrahydrofuran, Dichloromethane or chloroform.

A preparation method of a novel 5-thio-1,4,5-trisubstituted 1,2,3-triazole, the steps are as follows:

In organic solvents, under the action of pentamethylcyclopentadienyl 1,5-cyclooctadienyl ruthenium chloride ([Cp*Ru(COD)Cl]) catalyst, thiocyanate-based internal alkynes The reaction of the compound with an organic azide generates a 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole in situ, the 5-thiocyanate-substituted 1,4, The 5-trisubstituted 1,2,3-triazole continues to react with Grignard reagent or lithium reagent to form a new 5-thio-1,4,5-trisubstituted 1,2,3-triazole. The reaction formula is as follows :

Wherein, R ¹ , R ² and R ³ are alkyl or aryl, and R ⁴ is alkyl;

I is a thiocyanate group internal alkyne compound;

IV is format reagent;

VI is lithium reagent;

The molar ratio of the thiocyanate group internal alkyne compound, organic azide compound and Grignard reagent or lithium reagent is 1:1.5:2-1:3:4, and the thiocyanate group internal alkyne compound The concentration in the system is 0.01-0.1 mmol/ml;

The dosage of the [Cp*Ru(COD)Cl] is 0.5-50 mol% of the alkyne compound in the thiocyanate group;

The reaction temperature is 0°C to room temperature, and the reaction time is 24h-36h, and a 5-thio-1,4,5-trisubstituted 1,2,3-triazole compound with a yield of not less than 62% is prepared.

Described organic solvent is benzene, toluene, ether, methyl tertiary butyl ether, dichloromethane, tetrahydrofuran, trifluorotoluene, cyclohexane, one or more mixing of petroleum ether, preferably solvent is tetrahydrofuran, Dichloromethane or chloroform.

Described Grignard reagent is the THF solution of 1.0mol/L phenylmagnesium bromide, the THF solution of 1.0mol/L methylmagnesium bromide, the THF solution of 1.0mol/L isopropylmagnesium bromide or 1.0mol/L Cyclopropylmagnesium bromide in THF.

The lithium reagent is a n-hexane solution of 2.5mol/L n-butyllithium.

Beneficial effects of the present invention: the preparation method of 5-thiocyanate-substituted 1,4,5-trisubstituted 1,2,3-triazole and 5-thio-1,4,5-triazole in the present invention The preparation method of the substituted 1,2,3-triazole has mild reaction conditions, and the product yield is not less than 62%. The reaction conditions of the preparation method are mild, green, and the reaction efficiency is high, which is more suitable for large-scale production requirements, and the prepared 5-thio-1,4,5-trisubstituted 1,2,3-triazole compounds have potential physiological activity.

Detailed ways

The specific embodiments of the present invention are further described below in conjunction with the technical solutions.

Example 1: Preparation of 5-thiocyanato-(1-benzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD) were added Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature for 12h, spin-dried and separated by column chromatography to obtain 48mg of a white solid product with a yield of 82%.

Mp=88-90°C.. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.98-7.95 (m, 2H), 7.55-7.48 (m, 3H), 7.42-7.37 (m, 5H), 5.80 (s, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 152.0, 133.4, 129.7, 129.3, 129.1, 129.0, 128.5, 127.9, 127.7, 112.3, 106.2, 53.6. HRMS(ESI-TOF) m/z calcd forC ₁₆ H ₁₂ N ₄ S(M+Na) ⁺ 315.0674, found 315.0679.

Example 2: Preparation of 5-thiocyanato-(1-benzyl)-4-p-methoxyphenyl-1H-1,2,3-triazole

Under air, 1-p-methoxyphenethynyl thiocyanate (0.2 mmol, 37.8 mg) was dissolved in tetrahydrofuran (2 mL), benzyl azide (0.3 mmol, 40.2 mg) and [Cp* Ru(COD)Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, reacted for 12h, spin-dried and separated by column chromatography to obtain 50mg of white solid product with a yield of 78%.

Mp=132-134°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.93 (d, J=8.0 Hz, 2H), 7.40-7.37 (m, 3H), 7.05 (d, J=8.0 Hz) , 2H), 5.79(s, 2H), 3.89(s, 3H). ¹³ C NMR (100MHz, CDCl ₃ ): δ160.8, 151.9, 133.5, 129.3, 129.1, 127.9, 121.0, 114.4, 111.3, 106.4, 55.4, 53.5. HRMS(ESI-TOF) m/z calcd for C ₁₇ H ₁₄ N ₄ OS(M+Na) ⁺ 345.0781, found 345.0784.

Example 3: Preparation of 5-thiocyanato-(1-benzyl)-4-p-methylphenyl-1H-1,2,3-triazole Phenylethynyl thiocyanate (0.2 mmol, 34.6 mg) was dissolved in tetrahydrofuran (2 mL), then benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD)Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, reacted for 12 h, and was separated by column chromatography after spin-drying to obtain 47 mg of a white solid product with a yield of 77%.

Mp=57-59°C. ¹ H NMR (400MHz, CDCl ₃ , TMS): δ 7.83 (d, J=8.0Hz, 2H), 7.40-7.32 (m, 5H), 7.31 (d, J=8.0Hz) , 2H), 5.78(s, 2H), 2.41(s, 3H). ¹³ C NMR (100MHz, CDCl ₃ ): δ154.6, 147.3, 134.2, 132.8, 130.3, 129.2, 129.1, 129.1, 128.9, 128.5, 127.9, 53.1, 21.9. HRMS(ESI-TOF) m/z calcd for C ₁₇ H ₁₄ N ₄ S(M+Na) ⁺ 329.0831, found 329.0835.

Example 4: Preparation of 5-thiocyanato-(1-benzyl)-4-p-bromophenyl-1H-1,2,3-triazole

Under air, 1-p-bromophenylethynyl thiocyanate (0.2 mmol, 47.2 mg) was dissolved in tetrahydrofuran (2 mL), and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru ( COD)Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, reacted for 12h, spin-dried and separated by column chromatography to obtain 52mg of white solid product with a yield of 71%.

Mp=156-158°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.83 (d, J=8.0 Hz, 2H), 7.64 (d, J=8.0 Hz, 2H), 7.41-7.35 (m , 5H), 5.78(s, 2H). ¹³ C NMR (100MHz, CDCl ₃ ): δ150.9, 133.2, 132.2, 129.3, 129.2, 129.1, 128.0, 127.5, 124.3, 112.5, 105.9, 53.6.HRMS (ESI-TOF )m/z calcd for C ₁₆ H ₁₁ BrN ₄ S(M+Na) ⁺ 392.9780, found 392.9781.

Example 5: Preparation of 5-thiocyanato-(1-benzyl)-4-m-methylphenyl-1H-1,2,3-triazole Phenylethynyl thiocyanate (0.2 mmol, 34.6 mg) was dissolved in tetrahydrofuran (2 mL), then benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD)Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, reacted for 12 h, and was separated by column chromatography after spin-drying to obtain 52 mg of a white solid product with a yield of 85%.

Mp=95-97°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.76 (s, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.41-7.34 (m, 6H), 7.28 -7.26(m, 1H), 5.78(s, 2H), 2.43(s, 3H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ152.1, 138.8, 133.5, 130.5, 129.3, 129.1, 128.9, 128.4, 127.9, 127.7,124.8,112.4,106.4,53.5,21.5.HRMS(ESI-TOF)m/z calcd for C ₁₇ H ₁₄ N ₄ S(M+Na) ⁺ 329.0832,found329.0836.

Example 6: Preparation of 5-thiocyanato-(1-benzyl)-4-o-methoxyphenyl-1H-1,2,3-triazole

Under air, 1-o-methoxyphenylethynyl thiocyanate (0.2 mmol, 37.8 mg) was dissolved in tetrahydrofuran (2 mL), benzyl azide (0.3 mmol, 40.2 mg) and [Cp* Ru(COD)Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, reacted for 12h, spin-dried and separated by column chromatography to obtain 49mg of white solid product with a yield of 76%.

Mp=103-105°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.64 (d, J=8.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.47-7.40 (m , 5H), 7.12(t, J=8.0Hz, 1H), 7.03(d, J=8.0Hz, 1H), 5.82(s, 2H), 3.85(s, 3H). ¹³ C NMR(100MHz, CDCl ₃ ):δ156.3,149.7,133.5,131.4,131.2,129.2,129.0,128.1,121.1,117.6,115.6,111.1,107.3,55.5,53.6.HRMS(ESI-TOF)m/z calcd forC ₁₇ H ₁₄ N ₄ OS( M+Na) ⁺ 345.0781, found 345.0784.

Example 7: Preparation of 5-thiocyanato-(1-p-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and p-methoxybenzyl azide (0.3 mmol, 48.9 mg) and [Cp* Ru(COD)Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, reacted for 12h, spin-dried and separated by column chromatography to obtain 52mg of yellow solid product with a yield of 80%.

Mp=75-77°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.96 (d, J=8.0 Hz, 2H), 7.54-7.48 (m, 3H), 7.36 (d, J=12.0 Hz) , 2H), 6.93(d, J=8.0Hz, 2H), 5.74(s, 2H), 3.81(s, 3H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 160.2, 151.8, 129.7, 129.6, 129.0, 128.6,127.7,125.4,114.6,112.2,106.5,55.4,53.1.HRMS(ESI-TOF)m/z calcd for C ₁₇ H ₁₄ N ₄ OS(M+Na) ⁺ 345.0781,found345.0783.

Example 8: Preparation of 5-thiocyanato-(1-p-chlorobenzyl)-4-phenyl-1H-1,2,3-triazole

Under air, 1-phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL), and p-chlorobenzyl azide (0.3 mmol, 50.1 mg) and [Cp*Ru ( COD)Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, reacted for 12h, spin-dried and separated by column chromatography to obtain 46mg of a yellow solid product with a yield of 71%.

Mp=107-109°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.96 (d, J=8.0 Hz, 2H), 7.54-7.50 (m, 3H), 7.41 (d, J=8.0 Hz) , 2H), 7.34 (d, J=8.0Hz, 2H), 5.78 (s, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 152.0, 135.3, 131.8, 129.8, 129.5, 129.4, 129.0, 128.4, 127.7 ,112.4,106.1,52.7.HRMS(ESI-TOF)m/z calcd for C ₁₆ H ₁₁ ClN ₄ S(M+Na) ⁺ 349.0285,found 349.0285.

Example 9: 5-thiocyanato-[1-(2,3,4,5-tetrahydro-1'-phenyl)]-4-phenyl-1H-1,2,3-triazo Preparation of azoles

1-Phenylethynylthiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, followed by the addition of secondary azide (0.3 mmol, 60.0 mg) and [Cp*Ru(COD) Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, reacted for 12h, spin-dried and separated by column chromatography to obtain 47mg of brown liquid product with a yield of 66%.

¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 7.89 (d, J=4.0 Hz, 2H), 7.51-7.45 (m, 3H), 7.25-7.18 (m, 5H), 6.47 (t, J= 4.0Hz, 1H), 6.07(t, J=4.0Hz, 1H), 2.60-2.54(m, 1H), 2.43-2.29(m, 3H), 2.10-2.05(m, 1H), 1.91-1.85(m , 1H). ¹³ C NMR (100MHz, CDCl ₃ ): δ151.2, 138.9, 133.7, 133.0, 129.5, 128.9, 128.7, 128.6, 127.8, 127.6, 126.0, 111.7, 107.1, 57.1, 30.6, 25.5, 18.1.HRMS ( ESI-TOF)m/z calcd for C ₂₁ H ₁₈ N ₄ S(M+Na) ⁺ 381.1144, found 381.1145.

Example 10: Preparation of 5-phenylthio-(1-benzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD) were added Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, and the reaction system was cooled to 0 °C after 12 h, phenylmagnesium bromide (0.4 mmol) was added, and after stirring at room temperature for 12 h, saturated ammonium chloride solution was added The reaction was quenched, extracted three times with dichloromethane, the organic layers were combined, dried over anhydrous sodium sulfate, and spin-dried to obtain 54 mg of a white solid product with a yield of 79%.

Mp=147-148°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 8.10 (d, J=8.0 Hz, 2H), 7.42-7.36 (m, 3H), 7.28-7.13 (m, 8H) , 6.90 (d, J=8.0 Hz, 2H), 5.61 (s, 2H). ¹³ C NMR (100 MHz, CDCl ₃ ): δ 150.8, 134.5, 133.6, 130.1, 129.5, 128.7, 128.7, 128.6, 128.3, 128.1, 127.0, 126.6, 126.5, 122.4, 52.3.

Example 11: Preparation of 5-phenylthio-(1-benzyl)-4-p-methoxyphenyl-1H-1,2,3-triazole

Under air, 1-p-methoxyphenethynyl thiocyanate (0.2 mmol, 37.8 mg) was dissolved in tetrahydrofuran (2 mL), benzyl azide (0.3 mmol, 40.2 mg) and [Cp* Ru(COD)Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, and the reaction system was cooled to 0 °C after 12 h, phenylmagnesium bromide (0.4 mmol) was added, and after stirring at room temperature for 12 h, saturated The reaction was quenched with ammonium chloride solution, extracted three times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, and spin-dried to obtain 54 mg of a yellow solid product with a yield of 73%.

Mp=94-95°C. ¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 8.04 (d, J=12.0 Hz, 2H), 7.28-7.21 (m, 5H), 7.16-7.12 (m, 3H) ,6.94(d,J=8.0Hz,2H),6.89(d,J=8.0Hz,2H),5.59(s,2H),3.83(s,3H).

Example 12: Preparation of 5-n-butylmercapto-(1-benzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD) were added Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, and the reaction system was cooled to 0 °C after 12 h, n-butyllithium (0.4 mmol) was added, and after stirring at room temperature for 12 h, saturated ammonium chloride solution was added to quench The reaction was quenched, extracted 3 times with dichloromethane, the organic layers were combined, dried over anhydrous sodium sulfate, spin-dried, and separated by column chromatography to obtain 42 mg of a yellow liquid product with a yield of 65%.

¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 8.15 (d, J=8.0 Hz, 2H), 7.45-7.41 (m, 2H), 7.36-7.29 (m, 6H), 5.68 (s, 2H) ,2.34(t,J＝8.0Hz,2H),1.26-1.21(m,2H),1.17-1.11(m,2H),0.68(t,J＝8.0Hz,3H).

Example 13: Preparation of 5-methylmercapto-(1-benzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD) were added Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, and the reaction system was cooled to 0 °C after 12 h, methyl magnesium bromide (0.4 mmol) was added, and after stirring at room temperature for 12 h, saturated ammonium chloride solution was added The reaction was quenched, extracted three times with dichloromethane, the organic layers were combined, dried over anhydrous sodium sulfate, and spin-dried to obtain 42 mg of a colorless liquid product with a yield of 76%.

¹ H NMR (400MHz, CDCl ₃ , TMS): δ 8.17-8.14 (m, 2H), 7.46-7.42 (m, 2H), 7.37-7.32 (m, 6H), 5.69 (s, 2H), 1.94 ( s, 3H).

Example 14: Preparation of 5-isopropylmercapto-(1-benzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD) were added Cl] (0.005 mmol, 1.9 mg), the reaction mixture was stirred at room temperature, and the reaction system was cooled to 0 °C after 12 h, and isopropylmagnesium bromide (0.4 mmol) was added. After returning to room temperature and stirring for 12 h, saturated ammonium chloride was added. The solution was quenched and extracted three times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, and spin-dried to obtain 41 mg of a yellow liquid product with a yield of 66%.

¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 8.19 (d, J=8.0 Hz, 2H), 7.45-7.41 (m, 2H), 7.37-7.32 (m, 6H), 5.68 (s, 2H) ,2.90-2.83(m,1H),1.02(d,J＝8.0Hz,6H).

Example 15: Preparation of 5-cyclopropylmercapto-(1-benzyl)-4-phenyl-1H-1,2,3-triazole

1-Phenylethynyl thiocyanate (0.2 mmol, 32.0 mg) was dissolved in tetrahydrofuran (2 mL) under air, and benzyl azide (0.3 mmol, 40.2 mg) and [Cp*Ru(COD) were added Cl] (0.005mmol, 1.9mg), the reaction mixture was stirred at room temperature, and the reaction system was cooled to 0°C after 12 hours of reaction, cyclopropylmagnesium bromide (0.4mmol) was added, and after stirring at room temperature for 12 hours, saturated ammonium chloride was added The solution was quenched and extracted three times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, and then spin-dried to obtain 38 mg of a colorless liquid product with a yield of 62%.

¹ H NMR (400 MHz, CDCl ₃ , TMS): δ 8.15 (d, J=8.0 Hz, 2H), 7.46 (t, J=8.0 Hz, 2H), 7.35-7.28 (m, 6H), 5.71 (s , 2H), 1.82-1.76 (m, 1H), 0.60-0.56 (m, 2H), 0.42-0.38 (m, 2H). ¹³ CNMR (100MHz, CDCl ₃ ): δ149.1, 135.4, 130.9, 128.8, 128.5, 128.4,128.3,127.7,127.2,126.6,52.1,16.1,8.4.HRMS(ESI-TOF)m/z calcd for C ₁₈ H ₁₇ N ₃ S(M+Na) ⁺ 330.1035,found330.1037.

Claims (7)

1. A preparation method of novel 5-thiocyanate substituted 1,4, 5-trisubstituted 1,2, 3-triazole is characterized by comprising the following steps:

in an organic solvent, under the action of a pentamethylcyclopentadienyl 1, 5-cyclooctadiene ruthenium chloride catalyst, catalyzing a reaction of a thiocyanato internal alkyne compound and an organic azide compound to prepare 5-thiocyanato substituted 1,4, 5-trisubstituted 1,2, 3-triazole, wherein the reaction formula is as follows:

wherein R is¹And R²Is alkyl or aryl, R¹And R²The same or different;

i is a thiocyanate radical internal alkyne compound;

the mol ratio of the thiocyanato internal alkyne compound to the organic azide compound is 1:1.5-1:3, and the concentration of the thiocyanato internal alkyne compound in the system is 0.01-0.1 mmol/ml;

the dosage of [ Cp, Ru, (COD) Cl ] is 0.5-50 mol% of the thiocyanato internal alkyne compound;

the reaction temperature is between room temperature and 80 ℃, the reaction time is between 12 and 24 hours, and the 5-thiocyanate substituted 1,4, 5-trisubstituted 1,2, 3-triazole with the yield not lower than 66 percent is prepared.

2. The method according to claim 1, wherein the organic solvent is one or more selected from benzene, toluene, diethyl ether, methyl tert-butyl ether, dichloromethane, tetrahydrofuran, trifluorotoluene, cyclohexane, and petroleum ether.

3. A preparation method of novel 5-thio-1, 4, 5-trisubstituted 1,2, 3-triazole is characterized by comprising the following steps:

in an organic solvent, under the action of a pentamethylcyclopentadienyl 1, 5-cyclooctadiene ruthenium chloride catalyst, a 5-thiocyanate substituted 1,4, 5-trisubstituted 1,2, 3-triazole is generated in situ by the reaction of a thiocyanate alkynes compound and an organic azide compound, the 5-thiocyanate substituted 1,4, 5-trisubstituted 1,2, 3-triazole continuously reacts with a lattice reagent or a lithium reagent to generate the novel 5-thio-1, 4, 5-trisubstituted 1,2, 3-triazole, and the reaction formula is as follows:

wherein R is¹,R²And R³Is alkyl or aryl, R⁴Is an alkyl group;

i is a thiocyanate radical internal alkyne compound;

IV is a Grignard reagent;

VI is a lithium reagent;

the mol ratio of the thiocyanato internal alkyne compound to the organic azide compound to the Grignard reagent or the lithium reagent is 1:1.5:2-1:3:4, and the concentration of the thiocyanato internal alkyne compound in the system is 0.01-0.1 mmol/ml;

the dosage of [ Cp, Ru, (COD) Cl ] is 0.5-50 mol% of the thiocyanato internal alkyne compound;

the reaction temperature is 0-room temperature, the reaction time is 24-36 h, and the 5-sulfo-1, 4, 5-trisubstituted 1,2, 3-triazole compound with the yield not less than 62 percent is prepared.

4. The method according to claim 3, wherein the organic solvent is one or more selected from benzene, toluene, diethyl ether, methyl tert-butyl ether, dichloromethane, tetrahydrofuran, trifluorotoluene, cyclohexane, and petroleum ether.

5. The process according to claim 3 or 4, wherein the Grignard reagent is a 1.0mol/L THF solution of phenylmagnesium bromide, a 1.0mol/L THF solution of methylmagnesium bromide, a 1.0mol/L THF solution of isopropylmagnesium bromide or a 1.0mol/L THF solution of cyclopropylmagnesium bromide.

6. The method according to claim 3 or 4, wherein the lithium reagent is a 2.5mol/L n-butyllithium n-hexane solution.

7. The method according to claim 5, wherein the lithium reagent is a 2.5mol/L n-hexane solution of n-butyllithium.